Bibliography

1. Anonymous. Abdominal pain, fever, and rash in a 39-year-old male [clinical 
conference]. Am J Med 1994; 97:300-306.

2. Anonymous. Human granulocytic ehrlichiosis--New York, 1995 [published erratum 
appears in MMWR Morb Mortal Wkly Rep 1995 Sep 8;44(35): 653]. MMWR Morb 
Mortal Wkly Rep 1995; 44:593-595.
Notes : Since 1986, two human tickborne diseases caused by Ehrlichia spp. have been 
recognized in the United States: human monocytic ehrlichiosis (HME), caused by E. 
chaffeensis, and human granulocytic ehrlichiosis (HGE), caused by an agent closely 
related to E. equi (1,2). In June 1995, the Westchester County (New York) Department 
of Health (WCDOH) received reports from physicians who were treating patients for 
suspected HGE. In response, the WCDOH sent information to all primary-care 
physicians in Westchester County describing the clinical and laboratory features of 
ehrlichiosis (fever, myalgia, headache, leukopenia, and thrombocytopenia) and 
requested that they voluntarily report suspected cases of ehrlichiosis. This report 
summarizes an investigation by the New York State Department of Health (NYSDOH) 
and the WCDOH of suspected ehrlichiosis cases and the clinical characteristics of 
confirmed and probable cases.

3. Anonymous. Fever, rash, testicular swelling, and eosinophilia in an 86-year-old man 
[clinical conference]. Am J Med 1996; 100:110-116.

4. Anonymous. Fever, rash, testicular swelling, and eosinophilia in an 86-year-old man 
[clinical conference]. Am J Med 1996; 100:110-116.

5. Abe J, Takeda T, Watanabe Y, Nakao H, Kobayashi N, Leung DY, et al. Evidence 
for superantigen production by Yersinia pseudotuberculosis. J Immunol 1993; 
151:4183-4188.
Notes : Yersinia pseudotuberculosis is an enteric pathogen that induces a variety of 
clinical symptoms, fever, scarlatiniform rash, diarrhea, vomiting, and arthritis. 
Characteristic histopathologic findings in Y. pseudotuberculosis infection such as 
lymphoid hyperplasia, typically seen in mesenteric lymph nodes, suggest that the 
stimulation of a large proportion of T lymphocytes may be involved in the pathogenesis 
of this infection. In this study, we assessed the mitogenic activity of culture 
supernatants of the clinical isolates of Y. pseudotuberculosis and investigated the 
mechanism by which these culture sups activate T cells. The culture sups, as well as 
partially purified fractions obtained by gel filtration, were found to selectively stimulate T 
cells bearing V beta 3, V beta 9, V beta 13.1, and V beta 13.2 compared with 
stimulation by anti-CD3. Furthermore, fibroblasts transfected with different HLA class II 
molecules, either HLA-DPw9, -DQw6, -DR1, or -DR4 Dw15, were capable of presenting 
Y. pseudotuberculosis culture supernatants to purified T cells. The T cell response to 
this sup was not restricted by donor HLA-DR types and was not neutralized by 
antibodies against the known staphylococcal superantigens, Staphylococcal 
enterotoxin (SE)A, SEB, SEC2, SED, SEE, and TSST1. These results suggest that Y. 
pseudotuberculosis produces superantigenic toxins that may mediate some of the 
systemic illnesses associated with infection by this organism.

6. Abram AC, Bellian KT, Giles WJ, Gross CW. Toxic shock syndrome after functional 
endonasal sinus surgery: an all or none phenomenon? Laryngoscope 1994; 104:927-
931.
Notes : Reported cases of toxic shock syndrome (TSS) following nasal surgery or 
functional endonasal sinus surgery (FESS) are uncommon. Classic TSS is a serious 
multisystem disorder resulting from Staphylococcus aureus phage I toxic shock 
syndrome toxin 1 (TSST-1), and it is characterized by fever, rash, hypotension, 
mucosal hyperemia, vomiting, diarrhea, and laboratory evidence of multisystem organ 

dysfunction. TSS cases following nasal surgery have been associated with nasal 
packing, mucosal barrier violation, prior S aureus phage I colonization, as well as low 
antitoxin antibody levels. Of the 1700 FESS procedures performed at our institution, 3 
cases were complicated by classic TSS, with 2 additional patients having a 
postsurgical course compromised by a milder degree of TSS. Diagnostic criteria, 
clinical presentation, management, and etiology are discussed, and the possibility of a 
continuum from mild-to-classic TSS is addressed.

7. al-Khaldi N, Watson AR, Harris A, Irving WL. Dual infection with human herpesvirus 
type 6 and parvovirus B19 in a renal transplant recipient. Pediatr Nephrol 1994; 8:349-
350.
Notes : A 7-year-old boy developed intermittent fever and rashes 2 weeks after anti-
lymphocyte globulin therapy for a transplant rejection episode. Dual infection with 
parvovirus B19 and human herpesvirus type 6 was suggested by serological tests. 
Neither virus has been reported previously in a symptomatic paediatric renal transplant 
recipient.

8. Anosike JC, Onwuliri CO. A probable case of vertical transmission of Onchocerca 
volvulus microfilariae. J Helminthol 1993; 67:83-84.
Notes : A probable case of vertical transmission of Onchocerca volvulus microfilariae in 
Dass Bauchi State, Nigeria is presented. A 28-week-old male child delivered by a 39-
year-old Fulani woman suffering from onchocerciasis was positive for O. volvulus 
microfilariae based on skin snip examinations. The child had general body pruritic rash 
and intermittent fever. Although the child's skin snip on re-examination five weeks later 
was also positive, the fever had gradually subsided.

9. Arellano F, Sacristan JA. Allopurinol hypersensitivity syndrome: a review. Ann 
Pharmacother 1993; 27:337-343.
Notes : OBJECTIVE: To review the pathophysiology, pathology, and clinical findings of 
allopurinol hypersensitivity syndrome (AHS), an infrequent but life-threatening adverse 
effect of allopurinol therapy. DATA SOURCES: A MEDLINE search (key terms 
hepatitis, interstitial nephritis, severe hypersensitivity, severe toxicity, vasculitis, toxic 
epidermal necrolysis, Lyell's syndrome, erythema multiforme, and Stevens-Johnson 
syndrome) was used to identify cases reported in the literature through the end of 1990. 
STUDY SELECTION: All cases evaluated met Singer and Wallace's diagnostic criteria 
for AHS. DATA EXTRACTION: We extracted data from 101 cases of AHS reported in 
the literature. The following information, when available, was analyzed: (1) patient data 
(age, gender, medical history), (2) treatment data (daily dosage of allopurinol, duration 
of treatment, indications, concomitant medications, and (3) adverse-event data. DATA 
SYNTHESIS: Patients were mostly middle-aged men with hypertension and/or renal 
failure receiving excessive doses of allopurinol primarily for asymptomatic 
hyperuricemia. Cutaneous rash and fever were the most common clinical findings. 
CONCLUSIONS: Although the pathophysiologic pathway leading to the development of 
AHS is unknown, it probably involves an immunologic mechanism following allopurinol 
accumulation in patients with poor renal function. Our findings suggest that the 
accepted diagnostic criteria for AHS may be too broad, and we recommend the 
application of more restrictive criteria. There is no effective treatment for AHS. The use 
of allopurinol only for accepted indications and in dosages adjusted for a patient's renal 
function may be the only means of minimizing the incidence of AHS.

10. Arias J, Fernandez-Rivas M, Panadero P. Selective fixed drug eruption to 
amoxycillin. Clin Exp Dermatol 1995; 20:339-340.
Notes : A selective fixed drug eruption to amoxycillin but not other betalactam drugs is 
reported. Penicillins are the drugs most frequently implicated in immunological adverse 
reactions. The most important of these are allergic reactions where an IgE-mediated 
mechanism is well established. Other immunological mechanisms have been described 
in reactions, such as haemolytic anaemia, serum sickness, drug-induced nephritis, 
drug fever and contact dermatitis. Fixed drug eruption (FDE) is a type of drug-induced 
dermatosis, the immunopathogenesis of which remains unknown. FDE is an 
uncommon reaction to penicillin derivatives, and very few cases have been reported. 
We present a case of a selective FDE to amoxycillin (AX), with no reaction to other 
betalactam drugs. Although one similar case has been reported, the reactivity to other 
penicillin derivatives was not assessed.

11. Arraga-Alvarado C. [Human ehrlichiosis. Review]. Invest Clin 1994; 35:209-222.
Notes : Human ehrlichiosis is a newly recognized tick-borne disease. Since 1935 
Ehrlichia canis has been known as a cause of illness in dogs and other canine 
species, and for a few years it was related with human disease. In 1990, Ehrlichia 
chaffeensis was isolated from a man suspected of having ehrlichiosis. Partial 
sequencing of the rRNAS from the human isolate and E. canis, indicated that they are 
98.7 related. More recently (May 1994) an human granulocytic ehrlichiosis have been 
reported in USA. PCR amplification and sequence of 16S rDNA, showed that the 
human isolate was virtually identical to those reported for E. phagocytophila y E. equi, 
organisms that cause ehrlichiosis in rumiant and in horses. Most patients shows fever, 
headache, malaise, nausea or vomiting, anorexia and in a minority of cases rash is 
present. Some of them have complications such as pulmonary infiltrates, 
gastrointestinal problems, renal dysfunction or failure, hepatoesplenomegaly, 
neurologic abnormalities, DIC and some times death. Leucopenia, thrombocytopenia 
and elevated liver enzyme values have been common findings. Tetracycline and 
cloramphenicol have been using in adults and children as especific theraphy.

12. Arya LS, Bhatia P, Jain Y, Chaudhary VP, Verma IC, Chinnappan D, et al. Juvenile 
chronic myelocytic leukemia--report of 10 cases. Med Pediatr Oncol 1995; 24:100-103.
Notes : Ten children (five boys and five girls) with juvenile chronic myelocytic leukemia 
were seen over a period of 12 years (1980-1991) at the All India Institute of Medical 
Sciences, New Delhi. With the exception of one who was aged 4.5 years, all children 
were below 4 years of age (mean age 20.4 months). The presenting features included 
fever, bleeding secondary to thrombocytopenia, marked hepatosplenomegaly, and skin 
rash. The striking hematological features were anemia, thrombocytopenia, peripheral 
blood monocytosis, and normoblastemia. There was no significant myeloid proliferation 
in the bone marrow aspirate (mean M:E = 5: 1), while erythroid proliferation was 
prominent along with monocytosis (mean 11.2%). Fetal hemoglobin was raised in 8 of 
the 10 patients (mean 14.1%). Long-term survival was poor, with maximum survival 
being 18 months in one case. New modalities of management of this rare entity are 
discussed.

13. Asano Y, Suga S, Yoshikawa T, Yazaki T, Uchikawa T. Clinical features and viral 
excretion in an infant with primary human herpesvirus 7 infection. Pediatrics 1995; 
95:187-190.
Notes : OBJECTIVE. To find clinical features of a virologically-confirmed patient with 
primary human herpesvirus 7 (HHV-7) infection and a relationship of the excretion of 
viruses between HHV-7 and human herpes-virus 6 (HHV-6). PATIENT AND METHODS. 
A 13-month-old boy who had a known prior history of exanthem subitum at 6 months of 
age developed fever for 3 days and a skin rash appeared as the fever was resolving. The 
course was accompanying with nonspecific signs and symptoms such as anorexia, 
irritability, mild diarrhea, palpebral edema, mild inflammation of pharynx, and mild 
occipital and cervical lymphadenopathy. Heparinized blood samples were used for 
isolation of HHV-6 and HHV-7 and detection of both virus DNA sequences by a nested 
polymerase chain reaction (PCR) amplification. Samples from other body sites were 
also tested for their DNA sequences using the PCR. Both virus antibody activity was 
measured by an indirect immunofluorescent assay or a neutralization test. RESULTS. 
Cultured mononuclear cells from the patient at the acute stage of the disease produced 
morphologic changes, which reacted only with the monoclonal antibody to HHV-7 but 
not with the antibody to HHV-6. Both viruses were not isolated from blood obtained at 
the convalescent stage. An antibody response of the patient indicated a seroconversion 
to HHV-7 but not to other microbial agents including HHV-6 and Mycoplasma 
pneumoniae. Both virus DNA sequences were detected in peripheral blood 

mononuclear cells at acute and convalescent stages. HHV-7 DNA was excreted into 
saliva and transiently into stool at an early convalescent stage followed by HHV-6 
excretion into saliva. No HHV-7 and HHV-6 was excreted into urine. CONCLUSIONS. 
Clinical features of a virologically confirmed patient with primary HHV-7 infection were 
comparable with those of primary HHV-6 infection and HHV-7 infection may reactivate 
HHV-6.

14. Asano Y, Yoshikawa T, Suga S, Kobayashi I, Nakashima T, Yazaki T, et al. 
Clinical features of infants with primary human herpesvirus 6 infection (exanthem 
subitum, roseola infantum). Pediatrics 1994; 93:104-108.
Notes : OBJECTIVE. To clarify clinical features of patients with primary human 
herpesvirus 6 (HHV-6) infection (roseola infantum, exanthem subitum) in a large-scale 
study. SUBJECTS AND METHODS. Clinical signs and symptoms were analyzed in 
176 infants in whom exanthem subitum was initially suspected and primary HHV-6 
infection was later confirmed. The infection was proved by isolation of the virus from 
blood, a significant increase in the neutralizing antibody titers to the virus, or both. 
RESULTS. The primary HHV-6 infection, which occurred throughout the year, was 
observed in 94 boys and 82 girls (mean age, 7.3 months). Fever developed in 98% 
(mean maximum fever, 39.4 degrees C) and lasted for 4.1 days. Macular or papular 

rashes appeared in 98%, on face, trunk, or both, mostly at the time of subsidence of 
the fever, and lasted for 3.8 days. Other clinical manifestations occurred as follows: 
mild diarrhea in 68%, edematous eyelids in 30%, erythematous papules in the pharynx 
in 65%, cough in 50%, and mild cervical lymph node swelling in 31%. Twenty-six 
percent had bulging of the anterior fontanelle and 8% had convulsions. CONCLUSIONS. 
Clinical features of patients with virologically confirmed exanthem subitum were 

comparable with those described before discovery of HHV-6.

15. Auer-Grumbach P, Pfaffenthaler E, Soyer HP. Pustulosis acuta generalisata is a 
post-streptococcal disease and is distinct from acute generalized exanthematous 
pustulosis. Br J Dermatol 1995; 133:135-139.
Notes : Generalized pustular eruptions with fever present a diagnostic and therapeutic 
problem. Based on a case of pustulosis acuta generalisata and a review of the 
literature, this entity can be regarded as an exclusively post-streptococcal disorder with 
an elevated antistreptolysin titre. It has a distinct clinical presentation of isolated 
pustules on normal skin, predominantly in an acral location. We propose criteria for the 
clear separation of this disease from acute generalized exanthematous pustulosis and 
from pustular psoriasis.

16. Barnard GF, Scharf MJ, Dagher RK. Sulfone syndrome in a patient receiving 
steroids for pemphigus. Am J Gastroenterol 1994; 89:2057-2059.
Notes : A male patient who was being treated with oral prednisone for erosive 
mucocutaneous pemphigus lesions developed fever, jaundice, a rash, and anemia 
within 2 wk of starting dapsone therapy. These signs are typical of the sulfone 
syndrome, which is a potentially fatal condition due to dapsone hypersensitivity. The 
incidence of sulfone syndrome is increasing in frequency but has not previously been 
reported in pemphigus. This patient developed the syndrome early and while on oral 
steroids, which are sometimes used as a treatment for the sulfone syndrome, and 
without any evidence of a hypersensitivity reaction. Physicians should be aware of the 
potentially fatal sulfone syndrome in patients who are on dapsone therapy and who 
have abnormal liver tests, fever, and a rash.

17. Berkelhammer C, Kher N, Berry C, Largosa A. Nortriptyline-induced fulminant 
hepatic failure. J Clin Gastroenterol 1995; 20:54-56.

Notes : We describe, to our knowledge, the first reported case of nortriptyline-induced 
fulminant hepatic failure. This tricyclic antidepressant drug was taken by a 
postmenopausal woman for 64 days before her presentation. The absence of fever, 
rash, or marked eosinophilia, the predominant zone 3 necrosis with bridging, and the 
latent period favor a metabolic idiosyncratic reaction. The fatal outcome underscores 
the importance of recognizing the association and discontinuing the offending agent.


18. Borgnolo G, Denku B, Chiabrera F, Hailu B. Louse-borne relapsing fever in 
Ethiopian children: a clinical study. Ann Trop Paediatr 1993; 13:165-171.
Notes : An outbreak of louse-borne relapsing fever, caused by the return to their original 
recruitment areas of soldiers at the end of 30 years of fighting in northern Ethiopia, was 
reported in the Arsi region. We studied 103 infants and children with louse-borne 
relapsing fever who were admitted to Asella Hospital between 1 May 1991 and 30 April 
1992. Twenty-one per cent of the patients had a clear history of contact with sick ex-
soldiers; 42% were students admitted to the hospital following the re-opening of 
schools after the summer vacation. The common clinical features of the disease were 
fever in 100%, headache in 84.5%, chills in 74%, abdominal pain in 51%, epistaxis in 
20%, hepatomegaly in 26%, splenomegaly in 14%, petechial rash in 34% and jaundice 
in 10%. Differences in symptoms and signs according to age are described. Observed 
complications were pneumonia in 14% and central nervous system involvement in 10%. 
Four children went into deep coma, and two of them died. Severe disease was 
associated with a high density of spirochaetes in blood smears. Patients were treated 
with two low doses of penicillin or one dose of penicillin followed by, according to age, 
chloramphenicol or tetracycline, and with intravenous fluids. The case fatality rate was 
1.9%. Jarisch-Herxheimer reactions occurred in 61% of patients. There were relapses 
in 2.9% of treated patients.

19. Borgnolo G, Hailu B, Ciancarelli A, Almaviva M, Woldemariam T. Louse-borne 
relapsing fever. A clinical and an epidemiological study of 389 patients in Asella 
Hospital, Ethiopia [see comments]. Trop Geogr Med 1993; 45:66-69.
Notes : An outbreak of louse-borne relapsing fever, due to the return of soldiers to their 
original recruitment areas, after the end of thirty years of fighting in northern Ethiopia, 
was reported in Arsi region, southern Ethiopia. The epidemic spread to different 
members of the community and eventually the schools. We studied 389 patients 
affected by the epidemic and who were admitted to Asella Hospital between June 1991 
and May 1992. Twenty-seven per cent of the patients were ex-soldiers; 28% were 
students, who were admitted to the hospital since the schools were opened after the 
summer vacations. The common clinical features of the disease were fever (99%), 
headache (92%), hepatosplenomegaly (66%), myalgia (55%), arthralgia (51%), 
petechial rash (43%), epistaxis (24%) and jaundice (23%). Observed complications 
were pneumonia (10%), pulmonary edema (6%), myocarditis (3%) and 6 abortions in 
15 pregnancies. Patients were treated with low dose penicillin and i.v. fluids. The in-
hospital case fatality rate was 3.6%. Jarisch-Herxheimer reaction occurred in 43% of 
the patients. 1.8% of the patients had relapses after treatment.

20. Brady WJ, DeBehnke D, Crosby DL. Dermatological emergencies. Am J Emerg 
Med 1994; 12:217-237.

21. Bray VJ, Singleton JD. Disseminated intravascular coagulation in Still's disease. 
Semin Arthritis Rheum 1994; 24:222-229.
Notes : Still's disease is characterized by arthritis, fever, rash, lymphoid hypertrophy, 
leukocytosis, and anemia, often in association with thrombocytosis. We describe a 
patient with Still's disease and thrombocytopenia secondary to disseminated 
intravascular coagulation (DIC). Fifteen definite cases of DIC complicating Still's 
disease have been reported in the English literature. Most developed this complication 
while receiving high doses of salicylates in association with hepatic dysfunction. In a 
few, the coagulopathy has been associated with gold therapy. Our patient is only the 
second reported to develop DIC in the absence of drug therapy and the fourth reported 
to die from this complication. The clinical features of these 16 patients are summarized 
and proposed mechanisms of pathogenesis are reviewed.

22. Carroll J, Thaler M, Grossman E, Alder A, Trau H, Rosenthal T. Generalized 
pustular eruption associated with converting enzyme inhibitor therapy. Cutis 1995; 
56:276-278.
Notes : A 67-year-old man presented with a high fever and a generalized rash. His 
extended hospital stay was characterized by fever with repeated staphylococcal 
bacteremia and the appearance of axillary lymphadenopathy and splenomegaly. Skin 
lesions became hyperpigmented, dry, and atrophic with areas of exfoliation and uclers. 
Examination of skin and lymph node biopsy specimens showed findings consistent 
with mycosis fungoides. The patient unexpectedly recovered on discontinuation of 

captopril. A positive macrophage inhibiting factor response for both captopril and 
enalapril indicated that the non-sulfhydryl moiety was the antigenic stimulant for the 
lesion resembling mycosis fungoides.

23. Caserta MT, Hall CB. Human herpesvirus-6. Annu Rev Med 1993; 44:377-383.
Notes : Human herpesvirus-6 (HHV-6), a mature T-cell lymphotropic virus, is a newly 
recognized member of the herpes virus family and shares limited homology with human 
cytomegalovirus. HHV-6 has been identified as the etiologic agent of the childhood 
illness exanthem subitum (roseola infantum). Widespread acquisition of this virus has 
been demonstrated to occur early in childhood, with fever as the most consistent 
manifestation of primary infection. Reactivation of latent infection has been postulated 
and may be associated with lymphoproliferative disorders or other diseases of immune 
function.

24. Caumes E, Carriere J, Guermonprez G, Bricaire F, Danis M, Gentilini M. 
Dermatoses associated with travel to tropical countries: a prospective study of the 
diagnosis and management of 269 patients presenting to a tropical disease unit. Clin 
Infect Dis 1995; 20:542-548.
Notes : The full spectrum of skin diseases related to travel in tropical areas is unknown. 
We prospectively studied 269 consecutive patients with travel-associated dermatosis 
who presented to our tropical disease unit in Paris during a 2-year period. The median 
age of these patients was 30 years; 137 patients were male; 76% of the patients were 
tourists; 38% had visited sub-Saharan Africa; and 85% had been appropriately 
vaccinated against tetanus. Cutaneous lesions appeared while the patient was still 
abroad in 61% of cases and after the patient's return to France in 39%. The diagnosis 
was definite in 260 cases; 137 of these cases (53%) involved an imported tropical 
disease. The most common diagnoses were cutaneous larva migrans (25%); 
pyodermas (18%); pruritic arthropod-reactive dermatitis (10%); myiasis (9%); tungiasis 
(6%); urticaria (5%); fever and rash (4%); and cutaneous leishmaniasis (3%). 
Hospitalization was necessary in 27 cases (10%), with a median duration of 5 days 
(range, 2-21 days). Travelers should be advised on how to avoid exposure to the agents 
and vectors of infectious dermatoses. Travel first-aid kits should include insect 
repellents and antibiotics effective against bacterial skin infections.

25. Chalasani P, Baffoe-Bonnie H, Jurado RL. Dapsone therapy causing sulfone 
syndrome and lethal hepatic failure in an HIV-infected patient. South Med J 1994; 
87:1145-1146.
Notes : A 34-year-old woman with HIV infection and no other opportunistic infections 
presented a classic sulfone syndrome, manifested by fever, rash, hemolytic anemia, 
and fulminant hepatitis due to dapsone hypersensitive reaction, with a fatal outcome. 
We believe this is the first reported fatal complication of dapsone in an HIV-infected 
patient. We to bring attention to this potentially fatal drug complication, which may 
become more common with widespread use of dapsone in HIV-infected patients. The 
package insert for dapsone recommends laboratory surveillance (hematologic and liver-
related tests) during the first 4 to 6 weeks of therapy, and every 3 to 4 months 
thereafter. Our case report suggests that closer follow-up of patients receiving dapsone 
might be indicated.

26. Cheong HI, Choi EH, Ha IS, Lee HJ, Choi Y. Acute renal failure associated with 
Yersinia pseudotuberculosis infection. Nephron 1995; 70:319-323.
Notes : Since 1987, we have experienced 11 children with acute renal failure (ARF) 
associated with Yersinia pseudotuberculosis (YP) infection. The illness began with the 
sudden onset of high fever, skin rash and gastrointestinal symptoms. Later in the 
course, periungual desquamation developed, mimicking Kawasaki disease. Elevated 
erythrocyte sedimentation rate, C-reactive protein and thrombocytosis were noticeable, 
and mild degrees of proteinuria, glycosuria and sterile pyuria were common. ARF, 
which typically developed about 1-3 weeks after the onset of fever, underwent a benign 
course with complete recovery. The renal biopsies mainly revealed findings of acute 
tubulointerstitial nephritis. YP should be considered as one of the causes of acute 
tubulointerstitial nephritis causing ARF, especially in children.

27. Choo DC, Chew SK, Tan EH, Lim MK, Monteiro EH. Oral acyclovir in the treatment 
of adult varicella. Ann Acad Med Singapore 1995; 24:316-321.
Notes : An open study was conducted to evaluate the efficacy of oral acyclovir in a 
group of 295 Singapore Armed Forces male servicemen. The 148 patients who were 
willing to take acyclovir were given 800 mg orally five times per day for seven days. The 
other 147 who refused to take acyclovir were monitored as a control group. Each of 
these groups was further classified into two groups. Group A patients presented with 
rash within 24 hours of rash onset and Group B presented between 24 and 72 hours. 
Daily lesion counts, temperature, pruritus scores and laboratory tests were used to 
monitor disease progression. Early acyclovir intervention (Group A) reduced the time to 
100% crusting from 7.19 to 5.71 days (P = 0.0001), decreased the maximum number 
of all lesions by 26% (P = 0.03) and the maximum number of vesicular lesions by 45% 
(P = 0.0004). Late therapy (Group B) was effective in reducing the maximum number of 
vesicular lesions by 38% (P = 0.003). The number of patients requiring antibiotics for 
suspected secondary skin infection, the duration of fever and paracetamol consumption 
were significantly reduced in both the early and late intervention groups. However, there 
were no effects in minimizing pruritus in either group. Serious complications such as 
pneumonia, encephalitis or death were not observed in this study. The most common 
adverse effect of acyclovir was mild diarrhoea occurring in 35% of patients treated with 
the drug. We conclude that early treatment with acyclovir was beneficial whereas late 
therapy had limited effect in reducing the severity of cutaneous lesions in patients with 
varicella.

28. Chow YM, Lin CY, Hwang B. Serum and urinary interleukin-6 (IL-6) levels as 
predicting factors of Kawasaki disease activity. Acta Paediatr Sin 1993; 34:77-83.
Notes : From January 1988 to Autumn 1991, 60 patients suffering from Kawasaki 
disease (KD) were recruited in this study. Their ages ranged from 4 months to 5 years. 
Diagnosis was based on the criteria revised in 1984 by the KD Research Committee in 
Japan. Of these, 12 cases developed coronary aneurysms. First, blood samples from 
60 KD patients were taken on admission before aspirin and/or intravenous 
immunoglobulin (IVIG) treatment. Convalescent blood samples were taken 3 months 
after onset of disease. The control group included (1) 10 cases of viral infection with 
skin rash and fever (aged 5 months to 5 years) and (2) 10 age and sex matched normal 
children admitted for elective pediatric surgery such as inguinal hernia. Second, urinary 
samples were collected from 32 cases during the acute phase of KD. Of these, 10 
cases had pyuria and/or proteinuria. The results showed that the serum IL-6 levels from 
KD patients during the first week of acute phase were significantly increased while 
undetectable in the convalescent sera and controls. There was also a statistical 
difference between the with and without coronary aneurysm groups during the first week 
(336.8 +/- 95.1 vs 125.5 +/- 56.5 pg/ml, P < 0.001). Urinary IL-6 levels were significantly 
elevated in KD patients with pyuria and/or proteinuria (156.6 +/- 77.7 pg/mg Cr) and 
undetectable in the group without pyuria and proteinuria and controls during the first 
week. There was no difference between with and without coronary aneurysm. These 
results suggest that serum IL-6 level is a useful factor for predicting formation of 
coronary aneurysm even within one week after onset of disease.(ABSTRACT 
TRUNCATED AT 250 WORDS).

29. Chuang LC, Tunier AP, Akhtar N, Levine SM. Possible case of procainamide-
induced intrahepatic cholestatic jaundice. Ann Pharmacother 1993; 27:434-437.
Notes : OBJECTIVE: To describe a possible case of procainamide-induced intrahepatic 
cholestatic jaundice that was recognized six weeks after the initiation of procainamide 
therapy and to summarize the five previously reported cases. CASE SUMMARY: A 77-
year-old woman with a history of hypertension, insulin-dependent diabetes mellitus, 
temporal arteritis, and Wolff-Parkinson-White syndrome who had taken procainamide 
for six weeks presented to the hospital with disorientation and acute renal and hepatic 
dysfunction. In addition to disorientation, scleral icterus, and diffuse maculopapular 
rash, her physical examination was generally normal. There was no evidence of fever, 
nausea, vomiting, lymphadenopathy, or eosinophilia. Her liver enzyme concentrations 
increased significantly from baseline (beginning of procainamide therapy). Her N-
acetylprocainamide (NAPA) concentration was elevated to 52 mg/L upon admission. 
Procainamide was discontinued and her NAPA concentration returned to within normal 
limits in two days. Diagnostic tests were performed to rule out active hepatitis, 
vasculitis, and liver malignancies. After procainamide was discontinued and prednisone 
treatment was started, she became more oriented and her liver enzyme concentrations 
slowly improved. DISCUSSION: Only five cases of procainamide-induced liver 
abnormalities have been previously reported; these included granulomatous hepatitis 
and intrahepatic cholestasis. The mechanism for liver dysfunction is not known; 
however, it is proposed to be a delayed hypersensitivity reaction. Clinical hallmarks of 
hypersensitivity include fever, eosinophilia, rash, and lymphadenopathy; nausea and 
vomiting also may be present. Of the five reported cases, all experienced fever and only 
one experienced pruritus. No patients had eosinophilia or lymphadenopathy. Because 
of the temporal increase in liver enzyme concentrations after six weeks of procainamide 
therapy, we believe that this case represents another possible procainamide-induced 
hypersensitivity reaction. CONCLUSIONS: Procainamide-induced liver dysfunction can 
occur from one day to six weeks after initiation of the drug and may subside one day to 
several weeks after discontinuation of therapy. Symptoms may include nausea, 

vomiting, rash, and fever. Liver enzyme concentrations are abnormal. It is important to 
recognize the possibility of such a reaction early so that procainamide therapy can be 
discontinued promptly to avoid further liver damage.

30. Conley BA, O'Hara S, Wu S, Melink TJ, Parnes H, Pardoe E, et al. Phase I trial of 
chloroguinoxaline sulfonamide, with correlation of its pharmacokinetics and 
pharmacodynamics. Cancer Chemother Pharmacol 1995; 37:139-149.
Notes : To define a maximum tolerable dose, chloroquinoxaline sulfonamide (CQS) was 
given as a 1-h infusion every 28 days to cancer patients for whom no effective standard 
therapy was available. Doses were escalated in cohorts of at least three patients each. 
Plasma for characterization of the pharmacokinetics of free and total CQS was 
obtained during and after the initial infusion and, when possible, during and after 
subsequent infusions of CQS if the dose had been reduced. A total of 101 courses of 
CQS in 55 patients were evaluated. Dose levels ranged from 18 to 3,700 mg/m2. The 
dose-limiting toxicity was hypoglycemia, first recognized at the 3,700-mg/m2 dose. 

When dose-limiting hypoglycemia was recognized, patients were entered at 
successively lower doses, with close monitoring of plasma glucose and insulin 
concentrations being done in 26 patients. Grade 1-3 hypoglycemia occurred within 4 h 
of the termination of CQS infusion and cleared by 24 h. Symptomatic hypoglycemia 
was more frequent at doses of CQS above 1,000 mg/m2. Concomitant administration of 
5% glucose did not ameliorate the hypoglycemia associated with CQS doses of > 
1,000 mg/m2. The total calorie intake, percentage of ideal body weight, or percentage 
of weight lost did not explain the incidence or severity of hypoglycemia in 12 patients in 
whom these data were obtained. Cardiac tachyarrhythmias occurred in 7 patients who 
received CQS at doses of > or = 1,000 mg/m2, and tachyarrhythmia was associated 
with hypoglycemia in 3 patients. Other toxicities were sporadic, but the frequency of 
toxicity was higher at CQS doses of > or = 1,000 mg/m2. These toxicities included 
fever, rash, lightheadedness, leukopenia, thrombocytopenia, alopecia, diarrhea, 
nausea, and vomiting. All toxicities were reversible. Mean peak plasma [CQS] and AUC 
increased with dose, with a suggestion that peak plasma [CQS] plateaued at higher 
doses. The decline in plasma [CQS] was fitted to a three-compartment, open linear 
model. The terminal half-life ranged from 28 to 206 h. Total body clearance ranged from 
44 to 881 ml/h with no evidence of saturation. Urinary excretion of the parent compound 
in 24 h averaged < 5%. CQS not bound to plasma protein (free CQS) comprised 1%-
17% of total plasma CQS and was not related to dose. A relationship was defined 
between the magnitude of hypoglycemia and CQS pharmacokinetic parameters. The 
percentage of decrease in plasma [glucose], i.e., (predose [glucose]-nadir 
[glucose]/predose [glucose]) x 100, correlated with both free and total peak plasma 
[CQS].(ABSTRACT TRUNCATED AT 400 WORDS).

31. Cronberg S, Banke S, Bruno AM, Carlsson M, Elmrud H, Elowsson S, et al. 
Ampicillin plus mecillinam vs. cefotaxime/cefadroxil treatment of patients with severe 
pneumonia or pyelonephritis: a double-blind multicentre study evaluated by intention-to-
treat analysis. Scand J Infect Dis 1995; 27:463-468.
Notes : In this double-blind multicentre study, using the intention-to-treat approach, a 
total of 293 patients with fever (> or = 38.5 degrees C), symptoms of sepsis and signs 
of pneumonia or pyelonephritis were randomly assigned to treatment with ampicillin and 
mecillinam (A+M) or cefotaxime followed by cefadroxil. In the febrile phase, treatment 
was given intravenously twice daily, either with 1,200 mg ampicillin together with 600 
mg mecillinam or with 2 g cefotaxime alone. When the patients stayed afebrile, the 
intravenous administration was replaced by oral treatment twice daily for 14 days, 
either with 500 mg pivampicillin and 400 mg pivmecillinam or 1 g cefadroxil. In the A+M 
group, 33% (48/144) of the patients did not complete the full course of treatment as 
compared with 32% (47/149) in the cephalosporin group, the reasons being treatment 
failure in 27 and 29, respectively, or adverse effects (n = 16 in both groups). The median 
duration of fever was 47 h in the A + M group and 50 h in the cephalosporin group. Of 
135 patients with pneumonia, 68% were completely cured in the A + M group, and 65% 
in the cephalosporin group, the main reasons for treatment failure being Mycoplasma 
pneumonia or ornithosis. Of 136 patients with pyelonephritis, 63% were cured in each 
group. The main reason for failure was bacteriological relapse. Side-effects were 
reported by 32 patients (22%) of the A+M group, as compared with 41 (28%) of the 
cephalosporin group. Epigastric complaints were equally frequent in both groups, but 
there was a tendency for a higher frequency of exanthema in the A+M group, and for 
antibiotic-associated diarrhoea and fungal superinfections in the cephalosporin group.

32. Dalton MJ, Clarke MJ, Holman RC, Krebs JW, Fishbein DB, Olson JG, et al. 
National surveillance for Rocky Mountain spotted fever, 1981-1992: epidemiologic 
summary and evaluation of risk factors for fatal outcome. Am J Trop Med Hyg 1995; 
52:405-413.
Notes : Between 1981 and 1992, the Centers for Disease Control collected and 
summarized 9,223 cases of Rocky Mountain spotted fever (RMSF) reported from 46 
states. Four states (North Carolina, Oklahoma, Tennessee, and South Carolina) 
accounted for 48% of the reports. The annual incidence per million U.S. population 
decreased from a high in 1981 of 5.2 to a low in 1992 of 2.0, primarily due to decreased 
incidence in the southeast. Case report forms were filed on 7,650 patients, of whom 
4,217 had laboratory-confirmed RMSF. The age group with the highest incidence was 
those 5-9 years of age. Most cases (90.0%) occurred between April 1 and September 
30 and included a history of tick attachment (59.6%). Reported symptoms included 
fever (94.0%), headache (86.2%), myalgia (82.5%), and rash (80.2%). The case-fatality 
ratio was 4.0%. Risk factors associated with death included older age, delay in 
treatment or no treatment, and treatment with chloramphenicol (compared with 
tetracycline); however, insufficient data existed to fully assess the confounding effect of 
severity of illness on antibiotic choice.

33. Davey KA, Barnett TM, Jackson MA. Case 02-1995: a 13-year-old boy with a fever 
and a rash [clinical conference]. Pediatr Emerg Care 1995; 11:121-126.

34. Dawson JE, Candal FJ, George VG, Ades EW. Human endothelial cells as an 
alternative to DH82 cells for isolation of Ehrlichia chaffeensis, E. canis, and Rickettsia 
rickettsii. Pathobiology 1993; 61:293-296.
Notes : Ehrlichia chaffeensis, etiologic agent of human ehrlichiosis, and Rickettsia 
rickettsii, etiologic agent of Rocky Mountain spotted fever (RMSF), are both tick-borne 
agents that cause nonspecific symptoms that may be indistinguishable from each 
other early in the course of infection. E. canis is a canine pathogen closely related to 
E. chaffeensis and was initially suspected of being the causative agent of human 
ehrlichiosis. If a febrile illness is reported, after tick exposure, neither ehrlichiosis nor 
RMSF can be immediately ruled out. When attempts are made to isolate the agent 
from blood, a very limited amount of blood is often available; we, therefore, sought a 
tissue-culture cell line that would support the growth of both R. rickettsii and E. 
chaffeensis. A newly established human microvascular endothelial immortal cell line 
(CDC/EU.HMEC-1) was evaluated for supporting the growth of both agents. Our results 
demonstrate that HMEC-1 supports the growth of R. rickettsii, E. chaffeensis, and E. 
canis and may be a useful tool for the isolation of these agents.

35. De Cuyper C, Hindryckx P, Deroo N. Febrile ulceronecrotic pityriasis lichenoides et 
varioliformis acuta. Dermatology 1994; 189 Suppl 2:50-53.
Notes : An unusually severe form of pityriasis lichenoides et varioliformis acuta 
(PLEVA) with a fatal outcome in an 82-year-old woman is reported. After a period of a 
mild eruption, extensive polymorphous, papular and ulcerohemorrhagic skin lesions 
developed, associated with intermittent high temperature and constitutional symptoms. 
Skin biopsies showed the typical histopathological changes of PLEVA. Early 
recognition of this severe variant of PLEVA is important, since the fulminating course 
can lead to death.

36. De Renzo A, Azzi A, Zakrzewska K, Cicoira L, Notaro R, Rotoli B. Cytopenia 
caused by parvovirus in an adult ALL patient. Haematologica 1994; 79:259-261.
Notes : A young woman in maintenance therapy for acute lymphoblastic leukemia in 
second complete remission developed fever and a skin rash associated with severe 
anemia, neutropenia and erythroblastopenia. A complete recovery was obtained in 4 
weeks' time after red cell transfusion, i.v. immunoglobulin and withdrawal of the 
maintenance chemotherapy. Parvovirus B19 infection was demonstrated by detection of 
B19 DNA in the patient's serum using a dot-blot hybridization assay and a nested 
polymerase chain reaction. Serological tests were positive for anti-B19 IgG but not for 
IgM. Erythroblastopenia due to parvovirus infection has already been reported in ALL 
patients. B19 infection should be suspected in leukemic patients if unexplained 
cytopenia (mainly anemia) follows an acute febrile illness. Very sensitive methods are 
often needed to confirm the diagnosis, since routine serological tests may be unreliable 

in immunocompromised patients.

37. De Vriese AS, Philippe J, Van Renterghem DM, De Cuyper CA, Hindryckx PH, 
Matthys EG, et al. Carbamazepine hypersensitivity syndrome: report of 4 cases and 
review of the literature. Medicine (Baltimore) 1995; 74:144-151.
Notes : We report 4 patients who developed a severe systemic hypersensitivity reaction 
when taking carbamazepine, To prove hypersensitivity to carbamazepine, we performed 
patch tests and in vitro lymphocyte transformation tests. Patch tests were uniformly 
and strongly positive in patients and negative in controls. Lymphocyte transformation 
tests were positive in 3 of 4 patients. We reviewed the literature on reports of 
carbamazepine-induced pseudolymphoma and other severe systemic hypersensitivity 
reactions. Considering the many common clinical, biochemical, and pathologic 
characteristics, we propose to group these reactions under the term "carbamazepine 
hypersensitivity syndrome." The syndrome is characterized by the development of 

fever, rash, and lymphadenopathy between 1 week and 3 months after the introduction 
of carbamazepine. A variety of other target organs may be involved, including the liver, 
kidneys, and lungs. The carbamazepine hypersensitivity syndrome is a clinical 
diagnosis. Patch tests and lymphocyte transformation tests are valuable tools to 
confirm the diagnosis, but are reliable only after all signs subside. Similar syndromes 
have been described with the other aromatic anticonvulsants (phenytoin, the other 
hydantoins, and phenobarbital), and there is evidence of a cross-reaction between 
carbamazepine and phenytoin. It is unknown whether the carbamazepine 
hypersensitivity syndrome should be considered a premalignant state, with an 
increased risk for the development of malignant lymphoma.

38. Doney KC, Storb R, Beach K, Anasetti C, Deeg HJ, Hansen JA, et al. A toxicity 
study of trimetrexate used in combination with cyclosporine as acute graft-versus-host 
disease prophylaxis in HLA-mismatched, related donor bone marrow transplants. 
Transplantation 1995; 60:55-58.
Notes : This study evaluated the acute toxicity of trimetrexate (TMTX) used in 
combination with cyclosporine (CsA) for prevention of acute graft-versus-host disease 
(GVHD) in patients undergoing allogeneic marrow transplantation from HLA-
mismatched, related donors. TMTX has a mechanism of action similar to that of 
methotrexate (MTX); however, unlike MTX, TMTX is not primarily dependent on renal 
excretion. Patients were conditioned for transplant with cyclophosphamide, anti-
thymocyte globulin, and total body irradiation. TMTX, 10 mg/m2 i.v., was administered 
on days 1, 3, 6, 11, 18, 25, 32, and 39 after transplant. CsA, 1.5 mg/kg i.v., was 
administered every 12 hr beginning on day-1. Eleven patients with hematologic 
malignancies or aplastic anemia (median age = 34 yr) received TMTX. Toxicity 
assessed included nausea, vomiting, fever, rash, time to myeloid and platelet 
engraftment, mucositis, and hepatic and renal dysfunction. Toxicity of TMTX was not 
different from that observed with MTX in a similar patient population. One patient died 
on day 16 before engraftment. The other 10 patients all engrafted and all developed 
acute GVHD at a median time of 11 days after transplant. The major manifestation of 
acute GVHD was in the skin, and all but one patient responded to primary therapy with 
corticosteroids. Seven patients have survived a median of 447 days after transplant. No 
significant toxicity from TMTX was observed. Further trials are warranted to define the 
role of TMTX in marrow transplantation.

39. Drabick JJ, Magill AJ, Smith KJ, Nutman TB, Benson PM. Hypereosinophilic 
syndrome associated with HIV infection. Military Medical Consortium for Applied 
Retroviral Research. South Med J 1994; 87:525-529.
Notes : A hypereosinophilic syndrome associated with dermatitis has been observed 
rarely in association with HIV infection. We describe the case of a young man with 
AIDS who came to us with a diffuse cutaneous eruption, fever, angioedema, 
eosinophilia, and a mildly elevated serum IgE level. No allergic or infectious cause of 
this illness could be determined, and the patient was treated with corticosteroids and 
PUVA therapy, resulting in complete resolution of the dermatitis and associated 
findings. In this case, there were clinical and histopathologic similarities to the 
idiopathic hypereosinophilic syndrome and to acute graft-versus-host disease. The 
serum level of the cytokine interleukin-5 (IL-5), which is associated with eosinophil 
production, was found to be mildly elevated during the peak of the eruption, while 
samples drawn previously and subsequently were not. Although it appears that the 
syndrome we describe is associated with the measurably elevated level of IL-5, further 
investigation is required to determine whether there is a cause and effect relationship 
between IL-5 and this entity. A brief review of the literature concerning eosinophils and 
HIV infection is also presented in the context of this case.

40. Dumler JS, Bakken JS. Ehrlichial diseases of humans: emerging tick-borne 
infections. Clin Infect Dis 1995; 20:1102-1110.
Notes : The ehrlichioses are emerging zoonotic infections that are caused by obligate 

intracellular bacteria in the genus Ehrlichia. Two human ehrlichioses occur in the 
United States: monocytic ehrlichiosis (HME), which is caused by Ehrlichia chaffeensis 
that infects mononuclear phagocytes in blood and tissues, and granulocytic 
ehrlichiosis (HGE), an infection of granulocytes that is due to a phylogenetically 
distinct organism. Both infections cause undifferentiated fever with leukopenia, 
thrombocytopenia, and elevations in serum aminotransferase levels. Rash is an 
infrequent sign, and vasculitis is exceedingly rare. Severe or fatal ehrlichiosis is 
associated with secondary or opportunistic infections and delayed therapy. Ticks are 
the likely vectors, and deer are the likely reservoirs. HGE is associated with Ixodes 
species ticks and Lyme disease, a finding suggesting concurrent infection. In cases of 
HME, ehrlichial inclusions (morulae) are rarely detected; however, they are often seen 
in neutrophils of patients with HGE. A clinical diagnosis is confirmed with use of the 
polymerase chain reaction during the infection or by serology during convalescence. 
Therapy with doxycycline is highly efficacious.

41. Dumler JS, Dawson JE, Walker DH. Human ehrlichiosis: hematopathology and 
immunohistologic detection of Ehrlichia chaffeensis. Hum Pathol 1993; 24:391-396.
Notes : Human ehrlichiosis is a recently described zoonosis caused by a rickettsia 
that infects leukocytes. Most patients have fever, headache, chills, and myalgias and 
develop leukopenia, thrombocytopenia, anemia, and elevations in serum hepatic 
aminotransferases. The cause of the peripheral leukopenia and thrombocytopenia is not 
known. We studied peripheral blood smears, bone marrow aspirates, and bone marrow 
biopsy specimens from patients with serologically proven ehrlichiosis to characterize 
the pathologic changes associated with leukopenia or thrombocytopenia, to detect the 
presence of immunohistologically demonstrable ehrlichiae, and to establish the infected 
host target cell(s). Specimens were obtained from 12 patients, and immunohistology for 
Ehrlichia chaffeensis was performed on tissue sections, aspirated bone marrow, and 
peripheral blood smears. Mean leukocyte and platelet counts available for nine patients 
were white blood cell count 3,300/microL (range, 1,100 to 10, 300/microL) and platelets 
61,000/microL (range, 40,000 to 82, 000/microL). Findings included myeloid 
hyperplasia (eight cases), megakaryocytosis (seven cases), granulomas (eight cases), 
marrow histiocytosis (one case), myeloid hypoplasia (one case), pancellular hypoplasia 
(one case), and normocellular marrow (two cases). Morulae of E chaffeensis were 
detected in four of 10 cases examined by immunohistology. Most ehrlichiae were 
detected within histiocytes, although morulae were rarely present within lymphocytes. 
Leukopenia, thrombocytopenia, or pancytopenia apparently most often results from 
peripheral sequestration or destruction; however, hypoplasia of marrow elements is 
present occasionally. Immunohistologic demonstration of E chaffeensis offers a direct 
means for establishing the etiologic diagnosis. These observations show the relatively 
frequent occurrence of bone marrow granulomas and suggest that infection of cells of 
the reticuloendothelial system may participate in the pathogenesis of human 
ehrlichiosis.

42. Dumler JS, Walker DH. Diagnostic tests for Rocky Mountain spotted fever and 
other rickettsial diseases. Dermatol Clin 1994; 12:25-36.
Notes : Rickettsial diseases continue to confound physicians because of their usually 
sporadic occurrence and nonspecific clinical presentation. In past years, diagnosis was 
confirmed only during convalescence; however, newer, more widely available methods, 
such as antigen detection and improved in vitro cultivation, have enabled a diagnosis at 
a time when therapeutic decisions are made. Molecular nucleic acid-based techniques 
have also expanded the spectrum of etiologic agents and illnesses caused by 
rickettsiae.

43. Eissa MM, Lawrence JM, 3rd, McKenzie L, Little FM, Mankad VN, Yang YM. 
Systemic lupus erythematosus in a child with sickle cell disease. South Med J 1995; 
88:1176-1178.
Notes : Although sickle cell disease (SCD) and systemic lupus erythematosus (SLE) 
are two distinct chronic diseases, many clinical features are common to both 
conditions. We describe a young patient who had a mild clinical course of SCD until 
SLE developed when he was 15 years old. His initial manifestations of SLE including 
fever, chest pain, and lung infiltration with pleural effusion were thought to be 
complications of SCD. However, a deteriorating clinical course, presence of facial and 
truncal rash, and persistent pleural effusion led to the diagnosis of SLE. We compare 
our case and the 10 previously reported cases and discuss the possible association of 
complement defects and the pathogenesis of SLE in patients with SCD. Our report 
illustrates the importance of considering other disease processes when clinical features 
are atypical of SCD.

44. Ekert H, Fok T, Dalla-Pozza L, Waters K, Smith P, White L. A pilot study of 
EVAP/ABV chemotherapy in 25 newly diagnosed children with Hodgkin's disease. Br J 
Cancer 1993; 67:159-162.
Notes : Twenty five children with newly diagnosed Hodgkin's disease were clinically 
staged and treated with a chemotherapy protocol designed to reduce delayed toxicity. 
Four patients without macroscopic residual disease after biopsy received three cycles 
of hybrid EVAP/ABV. All remain in CR 31-46 months from diagnosis. One other 
developed fever and rash considered to be due to Ara-C and was treated with MOPP. 
Twenty patients had macroscopic residual disease after biopsy and were treated with 
two cycles of EVAP alone and reassessed with imaging and gallium scans. Twelve 
achieved CR, seven PR and one was not evaluable. Patients in CR were subsequently 
treated with 2-4 cycles of hybrid EVAP/ABV, while those in PR received 3-4 cycles. At 
a median follow up of 37 months the overall survival was 100%, relapse free 79% and 
treatment failure free 60%. Eight patients had mediastinal widening > 1/3 thoracic 
width. At the completion of the protocol five achieved CR, two PR and one was 
withdrawn from study at investigator preference. One patient has subsequently 
relapsed. Of the evaluable ten patients without a mediastinal presentation all achieved 
CR but three relapsed at 10, 13 and 18 months from diagnosis. Patients who achieved 
a PR only, relapsed or were withdrawn from study have been salvaged with MOPP or 
Ch1VPP chemotherapy.

45. Enright H, Jacob HS, Vercellotti G, Howe R, Belzer M, Miller W. Paraneoplastic 
autoimmune phenomena in patients with myelodysplastic syndromes: response to 
immunosuppressive therapy. Br J Haematol 1995; 91:403-408.
Notes : We analysed the clinical features, course and response to immunosuppressive 
therapy in 30 patients with autoimmune disorders associated with myelodysplastic 
syndromes (MDS). 18 patients with MDS developed acute systemic autoimmune 
disorders. Common manifestations were skin vasculitis (n = 15) and arthritis (n = 11). 
Seven patients had an acute clinical syndrome of vasculitic skin rash, fever and arthritis 
with peripheral oedema in three and pulmonary infiltrates in five of these seven patients. 
Other acute manifestations included pericarditis, pleural effusions, skin ulceration, 
seizures, myositis and peripheral neuropathy. Chronic or isolated autoimmune 
manifestations (n = 11) included glomerulonephritis, polyneuropathy, pyoderma 
gangrenosum, ulcerative colitis and polyarthritis. Classic connective tissue disorders 
recognized included relapsing polychondritis, polymyalgia rheumatica, Raynaud's 
syndrome and Sjogren's syndrome. Autoimmune manifestations responded to 
immunosuppressive therapy (primarily prednisone) in 26/27 patients treated. 
Furthermore, cytopenias improved substantially in six patients, including complete 
normalization of peripheral blood counts in two patients with cytogenetic remission in 

one. Patients with a haematological response to immunosuppressive therapy had 
improved survival compared with non-responding patients. The autoimmune syndrome 
was implicated as a primary cause of death in 8/17 patients who died. Autoimmune 
manifestations may be more common than previously recognized in patients with MDS. 
Aggressive therapy with immunosuppressive agents in selected patients often controls 
autoimmune phenomena associated with MDS and may lead to haematological 
responses in some patients.

46. Everett ED, Evans KA, Henry RB, McDonald G. Human ehrlichiosis in adults after 
tick exposure. Diagnosis using polymerase chain reaction. Ann Intern Med 1994; 
120:730-735.
Notes : OBJECTIVE: To identify and prospectively follow patients with suspected 
human ehrlichiosis regarding clinical manifestations, laboratory variables, methods for 
confirming the diagnosis, and complications. DESIGN: Prospective case study. 
SETTING: University and Veterans Affairs hospital and clinics. PATIENTS: 
Observations in 30 adult patients with acute febrile illness or with unexplained fevers 
and cytopenias or abnormal liver profiles or both. MEASUREMENTS: Serial clinical 
examinations, hematologic profiles, liver profiles, electrolyte determinations, chest 
radiographs, and response to therapy; other studies appropriate for patient care. 
INTERVENTION: Therapy with doxycycline. RESULTS: Thirty cases of ehrlichiosis 
were identified between 1989 and 1992. Tick exposure was strongly associated with 
the illness (P = 0.0001). Symptoms were nonspecific; fever, chills, and headache 
predominated but many other symptoms also occurred. Fever and skin rashes with 
various morphologic characteristics were the most common physical findings. 
Laboratory investigations indicate that the hematologic, hepatic, and central nervous 
systems are commonly involved in human ehrlichiosis. Twenty of 23 patients (87 ) 
tested by the polymerase chain reaction using Ehrlichia chaffeensis sequences and 
whole blood samples were positive for E. chaffeensis. CONCLUSIONS: The syndrome 
of human ehrlichiosis is not commonly recognized by physicians. Ehrlichiosis should 
be considered in the differential diagnosis of patients with febrile illness after known or 
possible tick exposure, particularly if accompanying cytopenias or abnormal liver 
profiles or both are present. The therapeutic response to doxycycline is prompt, and 
complications are uncommon in promptly treated patients. The polymerase chain 
reaction applied to whole blood samples is a promising test for rapid confirmation of the 
diagnosis within 24 to 48 hours.

47. Ewert DP, Westman S, Frederick PD, Waterman SH. Measles reporting 
completeness during a community-wide epidemic in inner-city Los Angeles. Public 
Health Rep 1995; 110:161-165.
Notes : A study was undertaken to determine the extent of measles underreporting 

among preschool-age children. In two community surveys conducted in inner-city Los 
Angeles during 1990 and 1991, respondents were asked whether preschool-age 
children in their households had ever been ill with measles. Information about measles 
episodes was obtained and medical records were reviewed, when available. A probable 
measles case was defined as having 3 or more days of rash with fever of 38.3 degrees 
centigrade or greater, and either cough, coryza, or conjunctivitis. To determine the 
proportion of cases reported, probable measles cases identified were matched with 
measles cases reported to the Los Angeles County Department of Health Services. Of 
the 947 children ages 6 weeks through 59 months included in the surveys, 35 children 
had experienced an illness episode which met the probable measles case definition. 
Ten (29 percent) of the 35 probable measles cases were reported to the health 
department. Hospitals reported 9 (69 percent) of 13 probable measles cases evaluated 
while private physicians' offices reported 0 (0 percent) of 12 evaluated (Fisher's exact 
test, P < 0.001), although 5 children were seen by private physicians before rash onset. 
Reporting was more complete for cases occurring during 1990 and 1991 (33 percent) 
than from 1987 through 1989 (18 percent). The hospitalization rate for preschool-age 
children with probable measles cases in the catchment area was estimated to be 8 
percent (95 percent confidence interval = 0 to 18 percent).(ABSTRACT TRUNCATED 

AT 250 WORDS).

48. Feldman S. Acyclovir therapy for varicella in otherwise healthy children and 
adolescents. J Med Virol 1993; Suppl 1:85-89.
Notes : Acyclovir has been approved in the United States and elsewhere as antiviral 
therapy for otherwise healthy children and adolescents with varicella. This development 
arose from multicentre placebo-controlled trials of acyclovir in normal patients, 2-18 
years of age, which showed that the drug accelerated cutaneous healing, and reduced 
fever and related constitutional symptoms without harmful side effects. Acyclovir did 
not, however, decrease transmission of chickenpox within the household, nor was there 
any demonstrable effect of antiviral therapy on varicella complications. In this article, 
the background and rationale for the multicentre studies of acyclovir in normal 
paediatric patients with chickenpox is reviewed. The evidence for and against its routine 
administration within 24 hours of the eruption of skin rash is also discussed.

49. Ferson MJ, Young LC, Robertson PW, Whybin LR. Difficulties in clinical diagnosis 
of measles: proposal for modified clinical case definition. Med J Aust 1995; 163:364-
366.
Notes : OBJECTIVE: To examine the accuracy of clinical diagnosis of measles and to 
develop an improved measles clinical case definition. DESIGN: Case survey. SETTING: 
Eastern Sydney, December 1990 to August 1993. SUBJECTS: All cases of measles 
notified to the Eastern Sydney Public Health Unit without or before serological 
confirmation. OUTCOME MEASURES: Demographic and clinical details, measles- and 
rubella-specific IgM and measles complement fixation titres in acute and convalescent 
(when available) sera and epidemiological links with confirmed measles cases. 
RESULTS: Of 49 subjects reported and with complete follow-up, 24 were confirmed 
with measles, four with rubella and 21 had no definite diagnosis. Clinical diagnosis of 
measles had a false positive rate of 51%. Subjects with confirmed measles were 
significantly more likely to have a cough (23/24) than those with no definite diagnosis 
(15/21; P = 0.03) and to be febrile on the day of rash onset (23/24 versus 10/21; P = 
0.001). The Centers for Disease Control definition had a sensitivity of 92% but 
specificity of only 24%. A modified case definition of rash, cough and fever present at 
onset of rash had equal sensitivity but greater specificity (57%). CONCLUSIONS: As 
measles is no longer common in Australia, clinical diagnosis is unreliable. When a 
public health response is needed, cases should be confirmed by serological tests or, if 
not available, we propose use of our modified clinical case definition.

50. Fichtenbaum CJ, Peterson LR, Weil GJ. Ehrlichiosis presenting as a life-
threatening illness with features of the toxic shock syndrome [see comments]. Am J 
Med 1993; 95:351-357.
Notes : OBJECTIVE: To describe clinical and laboratory features of patients with severe 
ehrlichiosis, some of whom presented with toxic shock syndrome (TSS)-like illnesses, 
and to report, to our knowledge, the first documented fatal case of ehrlichiosis in a 
child. DESIGN: Case series. SETTING: Tertiary-care medical center. PATIENTS: All 
patients with documented ehrlichiosis during a 3-year period, August 1, 1989, to July 
31, 1992. RESULTS: Eight patients (age range: 2 to 46 years) met clinical and 
serologic diagnostic criteria for ehrlichiosis. The mean interval from first contact with a 
physician to initiation of appropriate antibiotic therapy was 4.6 days (range: 1 to 11 
days). All eight patients with ehrlichiosis had fever, chills, thrombocytopenia, and 
abnormal liver function test results. Most patients also had rash (seven), conjunctival 
hemorrhage or erythema (six), and leukopenia (six). Four cases met diagnostic 
dysfunction. Two patients required mechanical ventilation, and one of these, a 6 1/2-
year-old boy, died of complications of the infection. A ninth patient with probable 
ehrlichiosis also met diagnostic criteria for TSS. CONCLUSIONS: Human ehrlichiosis 
can present as a severe, life-threatening illness that may resemble TSS. The diagnosis 
of ehrlichiosis was not considered by the physicians who first cared for these patients. 
Greater awareness of the potential severity of ehrlichiosis is needed to ensure that 
proper treatment is initiated early in the course of the disease.

51. Fiscus SA, Heggem-Snow A, Troiani L, Wallmark E, Folds JD, Sheff B, et al. 
Transient high titers of HIV-1 in plasma and progression of disease. J Acquir Immune 
Defic Syndr Hum Retrovirol 1995; 9:51-57.
Notes : Periodic quantitative HIV-1 plasma cultures were performed on 28 seropositive 
individuals who had CD4 cells < or = 300/mm3 and who were enrolled in three clinical 
trials testing the efficacy of didanosine versus zidovudine monotherapy. Most plasma 
cultures were negative or of low titer (1-100 tissue culture infective dose/ml of plasma), 
but there were 14 instances of high-titered plasma viremia (> or = 1,000 tissue culture 
infective dose/ml of plasma) seen in 11 individuals. These peaks in plasma culture 
titers were significantly associated either with rapidly decreasing CD4 cell numbers or 
with CD4 cells already < 50/mm3. In addition, patients who experienced these 
episodes of high-titered plasma viremia were more apt to have clinical complaints of 
fever, rash, flu-like illness, and/or opportunistic infection and also the syncytium-
inducing HIV-1 phenotype and progression of disease.

52. Fitzgerald DA, Heagerty AH, Stephens M, Smith AG. Follicular toxic pustuloderma 
associated with allopurinol. Clin Exp Dermatol 1994; 19:243-245.
Notes : Allopurinol is widely prescribed for primary and secondary hyperuricaemia, and 
cutaneous adverse reactions are seen in 0.8-2.1% of recipients. The majority of these 
are mild and include pruritus, diffuse or maculo-papular erythema, urticaria and 
ichthyosis. More severe reactions are well recognized and include exfoliative dermatitis, 
toxic epidermal necrolysis and a generalized hypersensitivity syndrome. The latter 
typically comprises fever, rash, hepatic and renal dysfunction and eosinophil 
leucocytosis. The occurrence of toxic pustuloderma due to allopurinol, confirmed by re-
challenge, is reported.

53. Frank GR, Cherrick I, Karayalcin G, Valderrama E, Lanzkowsky P. Transient 
erythroblastopenia in a child with Kawasaki syndrome: a case report. Am J Pediatr 
Hematol Oncol 1994; 16:271-274.
Notes : PURPOSE: We describe for the first time the case of a child with Kawasaki 
syndrome and associated transient erythroblastopenia. PATIENTS AND METHODS: A 
5 1/2-month-old infant with Kawasaki syndrome as evidenced by lymphadenopathy, 
fever, rash conjunctival injection, and extremity changes had associated anemia and 
reticulocytopenia requiring transfusion and thrombocytopenia. Bone marrow aspiration 
was consistent with a transient erythroblastopenia. She developed cardiac aneurysms 
despite therapy with i.v. immunoglobulin and aspirin. RESULTS: The anemia and 
reticulocytopenia resolved with normalization of her hemoglobin. The platelet count 
increased and she developed a thrombocytosis characteristic of this clinical entity. She 
completely recovered without recurrence of either the anemia or reticulocytopenia. 
CONCLUSIONS: We speculate that the cause of the erythroblastopenia and 
thrombocytopenia is an inflammatory insult of Kawasaki syndrome on the bone marrow 
and its various lineages causing the myriad hematological abnormalities now 
associated with Kawasaki syndrome. It is possible that the i.v. immunoglobulin aids in 
neutralizing the triggering agent and therefore shortening the duration of the marrow 
insult.

54. Fulton B, Wagstaff AJ, McTavish D. Trimetrexate. A review of its pharmacodynamic 
and pharmacokinetic properties and therapeutic potential in the treatment of 
Pneumocystis carinii pneumonia. Drugs 1995; 49:563-576.
Notes : Trimetrexate is a folinic acid analogue structurally related to methotrexate, 
whose primary mechanism of action is believed to be inhibition of dihydrofolate 
reductase. This reduces the production of DNA and RNA precursors and leads to cell 
death. Trimetrexate is lipophilic and can passively diffuse across cell membranes 
including those of Pneumocystis carinii and its mammalian host. To minimise toxicity, 
trimetrexate must be coadministered with calcium folinate (leucovorin calcium), a 
reduced folate coenzyme, which is transported into, and protects, mammalian host 
cells but not P. carinii cells. In noncomparative trials trimetrexate was effective in the 
treatment of P. carinii pneumonia (PCP) in patients with AIDS who were intolerant of or 
refractory to cotrimoxazole (trimethoprim/sulfamethoxazole) and pentamidine 
treatment. In these patients, 2- to 4-week survival rates of 48 to 69% were reported. In a 
comparative trial in the initial therapy of PCP, trimetrexate was less effective than 
cotrimoxazole in moderate to severe disease as evidenced by a significantly higher 
failure rate. Trimetrexate was better tolerated than cotrimoxazole when used in this 
setting, however. Significantly fewer patients receiving trimetrexate plus calcium folinate 
discontinued treatment because of adverse events than did patients receiving 
cotrimoxazole. The most common adverse effect associated with trimetrexate is 
myelosuppression (neutropenia and thrombocytopenia); this is mitigated by 
coadministration of calcium folinate and is generally reversible upon dosage reduction 
or discontinuation. Other adverse effects include increases in serum aminotransferase 
levels, anaemia, fever, rash/pruritus, and increased alkaline phosphatase or serum 
creatinine levels. Further research into the use of trimetrexate, including its efficacy as 
prophylaxis, in combination with other agents and as an oral formulation, is needed to 
clearly define its role in the treatment of PCP and to identify patients most likely to 
benefit. Currently, trimetrexate should be considered as an alternative treatment option 
in immunocompromised patients with moderate to severe PCP who have not responded 
to or are intolerant of first-line therapy.

55. Gabay C, De Bandt M, Palazzo E. Sulphasalazine-related life-threatening side 
effects: is N-acetylcysteine of therapeutic value? Clin Exp Rheumatol 1993; 11:417-
420.
Notes : This report is on a patient with a spondylarthropathy with peripheral joint 
involvement treated with sulphasalazine who developed severe hepatitis, disseminated 
intravascular coagulation, high spiking fever, a mononucleosis-like syndrome and a 
diffuse cutaneous rash. All these features resolved rapidly after drug withdrawal and 
intravenous N-acetylcysteine. Serious sulphasalazine-related adverse reactions are rare 
and their outcome is generally favourable within a few weeks after drug withdrawal. 
However, certain cases with life-threatening side effects may need additional treatment. 
The course in our patient suggests that N-acetylcysteine may be useful for treating 
sulphasalazine-induced side effects.

56. Gluckstein D, Ruskin J. Rapid oral desensitization to trimethoprim-
sulfamethoxazole (TMP-SMZ): use in prophylaxis for Pneumocystis carinii pneumonia 
in patients with AIDS who were previously intolerant to TMP-SMZ. Clin Infect Dis 1995; 
20:849-853.
Notes : Trimethoprim-sulfamethoxazole (TMP-SMZ) is the drug of choice as 
prophylaxis for Pneumocystis carinii pneumonia in patients with AIDS. However, 
adverse reactions ascribed to TMP-SMZ are common in such patients. We previously 
described a rapid method of oral TMP-SMZ desensitization in patients with AIDS and 
varying degrees of intolerance to the drug. To assess the feasibility, safety, and long-
term clinical utility of our desensitization protocol, we retrospectively studied 22 
consecutive patients who underwent desensitization. Prior to the procedure each of the 
study subjects had exhibited moderate to severe reactions to TMP-SMZ. 
Desensitization was successfully completed in 19 (86%) of the patients. The three 
patients for whom desensitization failed experienced chills and/or vomiting that resolved 
promptly with symptomatic therapy. One of the 19 patients was unavailable for long-
term follow-up. Of the remaining 18 patients, three discontinued taking TMP-SMZ within 
2 weeks of desensitization because of macular rash and fever. The other 15 (71%) of 
the evaluable patients tolerated both desensitization and subsequent prophylaxis and 
took TMP-SMZ for a mean of 14 months (in some cases, for as long as 41 months). 
None had P. carinii pneumonia while receiving TMP-SMZ. These results indicate that 
most patients who are presumed to be TMP-SMZ-intolerant can be rapidly desensitized 
with oral TMP-SMZ and subsequently receive the drug for protracted periods as 

effective prophylaxis for P. carinii pneumonia.

57. Gore SD, Donnenberg AD, Zehnbauer BA, Weng LJ, Burke PJ. Granulocyte-
macrophage colony-stimulating factor (GM-CSF), given concurrently with induction 
therapy for acute myelogenous leukemia (AML), augments the syndrome of T-
lymphocyte recovery. Leukemia 1994; 8:409-419.
Notes : A transient lymphocytosis precedes myeloid recovery in many patients with 
AML treated with intensive chemotherapy. We describe the kinetics, clinical features, 
and immunology of lymphocyte recovery which is markedly augmented by the inclusion 
of GM-CSF in induction therapy. Lymphocyte recovery from 19 patients receiving GM-
CSF as part of induction therapy was compared to a historical control of 25 patients 
treated with identical chemotherapy in the absence of cytokine. Kinetics and clinical 
features of lymphocyte recovery were analyzed. Peripheral blood was studied by flow 
cytometry, chromium release assays, and Southern analysis of the T-cell antigen 
receptor, beta chain gene. Patients treated with GM-CSF to recruit cells into cycle, 
exhibit markedly increased peaks of lymphocyte recovery. Recovering lymphocytes 
demonstrated an activated memory T-cell phenotype suggestive of a cytokine release 
syndrome. Lymphoid recovery was often associated with rash, fever, and 
lymphadenopathy. Study patients who developed peak lymphocyte counts > or = 1000 
microliters were more likely to achieve remission than those with a lower peak. 
Recovery lymphocytes did not lyse pretreatment autologous bone marrow cells. 
Southern analysis demonstrated dominant potentially clonal rearrangements in the 
majority of patients studied. Lymphocyte recovery, which appears to include oligoclonal 
expansion of memory T cells is markedly augmented by administration of GM-CSF 
during chemotherapy. This may represent a non-specific response by a limited 
repertoire of T cells surviving therapy, or a specific clonal response to a powerful 
exogenous or endogenous antigen. Possible antileukemic activity of these cells 
remains to be elucidated.

58. Griffin DE. Immune responses during measles virus infection. Curr Top Microbiol 
Immunol 1995; 191:117-134.
Notes : The characteristic disease features of measles--fever and rash--are associated 
with the immune response to infection and are coincident with virus clearance. MV-
specific antibody and CD4 and CD8 T cell responses are generated and contribute to 
virus clearance and protection from reinfection. During this same phase of immune 
activation immunologic abnormalities are also apparent. There is a generalized 
suppression of cellular immune responses that may contribute to increased 
susceptibility to other infections. Autoimmune disease may appear in the form of acute 
disseminated encephalomyelitis. If virus-specific immune responses are inadequate 
infection may progress with pulmonary or CNS manifestations, but without a rash. The 
pathogenesis of the rare disease SSPE, that occurs many years after primary infection 
is not clear, but immune responses show increased antibody to measles and cellular 
immune responses similar to those seen after uncomplicated infection.

59. Gross AS, Kagan SA, Hargreaves HK, Freedman A, Botstein GR, Fine RM. Fever, 
maculopapular eruption, and lymphadenopathy. Angioimmunoblastic lymphadenopathy 
(AILD). Arch Dermatol 1994; 130:1551, 1554

60. Gumru OZ, Kasaboglu C, Kocak H, Canbaz AE, Alatli C, Olgac V. Regional 
odontodysplasia. J Nihon Univ Sch Dent 1993; 35:209-212.
Notes : An unusual case of regional odontodysplasia in an 8-year-old boy is presented. 
He was referred to our clinic because of failure of tooth eruption on the left side of the 
maxilla and frequent fever attacks. Treatment consisted of extraction of the affected 
teeth, and removal of inflamed tissue.

61. Handfield-Jones SE, Jenkins RE, Whittaker SJ, Besse CP, McGibbon DH. The 
anticonvulsant hypersensitivity syndrome. Br J Dermatol 1993; 129:175-177.
Notes : Anticonvulsants can cause a characteristic hypersensitivity reaction. This 
multisystem reaction typically presents as fever, mucocutaneous eruptions, 
lymphadenopathy and hepatitis. There is cross-reactivity between different 
anticonvulsants, which complicates subsequent therapy. We report three cases to 
illustrate both the typical features, and less common complications, of this under-
recognized and life-threatening syndrome.

62. Hennessy S, Strom BL, Berlin JA, Brennan PJ. Predicting cutaneous 
hypersensitivity reactions to cotrimoxazole in HIV-infected individuals receiving primary 
Pneumocystis carinii pneumonia prophylaxis. J Gen Intern Med 1995; 10:380-386.
Notes : OBJECTIVES: To measure the incidence of cutaneous hypersensitivity 
reactions to cotrimoxazole in the setting of primary Pneumocystis carinii pneumonia 
(PCP) prophylaxis: to measure the incidence of severe reactions: and to identify 
predictors for these outcomes. DESIGN: Retrospective cohort study. SETTING: One 
university-based outpatient HIV clinic and one university-affiliated internal medicine and 
infectious disease medical practice. PATIENTS: Two hundred thirty-six HIV-infected 

individuals receiving cotrimoxazole for primary PCP prophylaxis. INTERVENTIONS: 
None. MAIN OUTCOME MEASURE: Occurrence of a cutaneous hypersensitivity 
reaction, defined as rash, fever, or pruritus that resulted in permanent discontinuation of 
cotrimoxazole. Severe reactions were defined as those resulting in hospital admission 
or systemic treatment with a corticosteroid. Cox regression was used to calculate 
relative rates (RRs) and 95% confidence intervals (CIs) for a number of clinical and 
laboratory variables. MEASUREMENTS AND MAIN RESULTS: Forty-eight (20%) 
subjects developed cutaneous hypersensitivity reactions, with six (12.5%) of these 
being severe. In the unadjusted analysis, the following factors demonstrated at least 
borderline association: male gender [RR (95% CI) = 0.46 (0.21-0.99)], higher CD4 
percentage [RR (95% CI) = 0.95 (0.90-1.00)], syphilis history [RR (95% CI) = 0.37 
(0.13-1.04)], and higher total protein [RR (95% CI) = 0.70 (0.45-1.09)]. Adjustment for 
potential confounding by measured variables did not meaningfully change these results. 
CONCLUSIONS: Cutaneous hypersensitivity reactions to cotrimoxazole in the setting 
of primary PCP prophylaxis are common. Although male gender, higher CD4 
percentage, syphilis history, and higher total protein have at least borderline 
associations with these reactions, routinely collected clinical and laboratory variables 
do not appear to be sufficiently associated with the reactions to permit development of 
a clinically useful prediction rule.

63. Holland JA, Bryan S, Huff-Slankard J. Nursing care of a child with 
meningococcemia. J Pediatr Nurs 1993; 8:211-216.
Notes : This case presentation will discuss the pathophysiology of a child in septic 
shock due to Neisseria meningitidis. The most prevalent nursing care concerns of this 
case encountered during the pediatric intensive care unit (PICU) and during the general 
floor stay will be addressed. The nursing skill required for identifying problems and 
planning care that clearly fall under the nursing domain also will be covered. In addition, 
the complexities of this case demonstrate that collaboration between the PICU nurse 
and the general pediatric nurse is imperative for successful patient outcome. A.W. was 
a 5 1/2-month-old infant transported to our PICU from a referral hospital in the state. 
Diagnosis at time of admission was meningococcemia, disseminated intravascular 
coagulopathy, septic shock, respiratory failure, and purpura fulminans. There was a 2- 
to 3-day history of a runny nose, cough, and vomiting. On the day of admission, A.W. 
had three seizures and developed a fever and a purpuric rash.

64. Hughes C. Rocky Mountain "spotless" fever with an erythema migrans-like skin 
lesion. Clin Infect Dis 1995; 21:1328-1329.
Notes : We report a case of Rocky Mountain "spotless" fever with a localized rash at 
the site of the tick bite that resembled the erythema migrans rash of Lyme borreliosis. 
Physicians who practice in geographic areas where Rocky Mountain spotted fever 
occurs should be aware of this unusual presentation.

65. Hughes WT, LaFon SW, Scott JD, Masur H. Adverse events associated with 
trimethoprim-sulfamethoxazole and atovaquone during the treatment of AIDS-related 
Pneumocystis carinii pneumonia. J Infect Dis 1995; 171:1295-1301.
Notes : Atovaquone was compared to trimethoprim-sulfamethoxazole (TMP-SMZ) for 
the relationship of time receiving therapy, plasma drug concentrations, and incidence of 
adverse reactions in patients with AIDS-associated Pneumocystis carinii pneumonia. 
Treatment-limiting adverse events occurred in 9% of atovaquone-treated patients and 
24% of TMP-SMZ-treated patients. Adverse events usually did not occur before day 7 
for either treatment. Only the incidence of rash increased with increasing plasma 
concentrations of atovaquone. The incidence of anemia, neutropenia, and azotemia 
increased with increasing trimethoprim plasma concentration, while other adverse 
events (gastrointestinal disorders, rash, fever, and liver function abnormalities) were 
independent of plasma drug concentration.

66. Huttenlocher A, Frieden IJ, Emery H. Neonatal onset multisystem inflammatory 
disease. J Rheumatol 1995; 22:1171-1173.
Notes : Neonatal onset multisystem inflammatory disease (NOMID) is a rare disorder 
involving a triad of arthropathy, rash, and central nervous system (CNS) involvement. 
We describe a girl with NOMID who presented with typical neonatal rash, arthropathy, 
fever, and failure to thrive, but has not developed evidence of ocular or CNS involvement. 
This case illustrates the spectrum of involvement seen in NOMID. Histopathology of the 
skin demonstrated neutrophilic eccrine hidradenitis, a unique finding, which may serve 
as a diagnostic clue in patients with this rare disorder.

67. Ingram CW, Haywood HB, 3d, Morris VM, Allen RL, Perfect JR. Cryptococcal 
ventricular-peritoneal shunt infection: clinical and epidemiological evaluation of two 
closely associated cases. Infect Control Hosp Epidemiol 1993; 14:719-722.
Notes : OBJECTIVE: To determine the cause of meningitis associated with 
Cryptococcus neoformans in two patients with recent ventricular-peritoneal (VP) shunt 
placement. DESIGN: A retrospective review of materials, records, and concurrent 
cases of VP shunt procedures. Isolates of C neoformans from each patient were 
submitted for analysis by colony morphology, biochemical testing, and karyotyping by 
pulsed-field electrophoresis. SETTING: Two 400-bed community hospitals. PATIENTS: 
Two immunocompetent patients presented with symptoms of progressive 
hydrocephalus in August 1991. Each received a VP shunt on the same day by the 
same surgeon using materials from a common vendor and hospital. RESULTS: Both 
patients presented within six to eight weeks with symptoms of fever, headache, rash, 
and cultures of cerebrospinal fluid (CSF) that yielded C neoformans. Each patient 
recovered after therapy with amphotericin B and flucytosine followed by several months 
of fluconazole, although one required replacement of the VP shunt for cure. Review of 
each patient's history and CSF characteristics at the time of shunt placement 
suggested reactivation of a preexisting infection. Isolates of C neoformans from each 
patient were submitted for analysis by colony morphology, biochemical testing, and 
karyotyping by pulsed-field electrophoresis. Each isolate was found to be unique by 
chromosomal karyotyping. CONCLUSIONS: Our data and previous reports suggest that 

cryptococcal VP shunt infections appear to be a complication of shunts placed in 
previously infected persons rather than nosocomial transmission of cryptococcus 
during placement.

68. Ishii M, Miyazaki Y, Yamamoto T, Miura M, Ueno Y, Takahashi T, et al. A case of 
drug-induced ductopenia resulting in fatal biliary cirrhosis. Liver 1993; 13:227-231.
Notes : A 50-year-old woman suffered from a diffuse skin rash, high fever and jaundice 
immediately after a second injection of glutathion and Stronger Neo-minophagen C 
which contains glycyrrhizin. Liver biopsy performed 11 months after the onset showed 
mild spotty hepatocyte necrosis, marked cholestasis in parenchyma, and some 
lymphocyte infiltration in the portal area. Interlobular bile ducts had undergone vacuolar 
degeneration or were absent in some portal tracts. In her hospital course, unremitting 
jaundice persisted and biliary cirrhosis developed with signs of portal hypertension; she 
died from liver failure 26 months after the onset. A liver specimen at her death revealed 
that most of the interlobular bile ducts had vanished. Based on the clinical course and 

pathology, drug-induced ductopenia, possibly due to an adverse reaction to 
glycyrrhizin, is the most likely diagnosis. While drug-related biliary cirrhosis is rarely 
fatal, this case presented an unusually rapid course of fatal biliary cirrhosis.

69. Jandrlic M, Kalenic S, Labar B, Nemet D, Jakic-Razumovic J, Mrsic M, et al. An 
autopsy study of systemic fungal infections in patients with hematologic malignancies. 
Eur J Clin Microbiol Infect Dis 1995; 14:768-774.
Notes : The aim of this study was to determine the incidence of fungal infections 
detected on autopsy in a group of 40 patients with hematologic malignancies treated 
with intensive chemotherapy or bone marrow transplantation, and to evaluate the risk 
factors for fungal infections. A control group included 38 patients with nonhematologic 
diseases and without granulocytopenia but with at least one of the known risk factors 
for fungal infections. Standard histopathological and microbiological methods were 
used. A higher incidence of invasive fungal infections was found in patients with 
hematologic malignancies as compared to the control group (p < 0.01). The 
predominant causes of fungal infections were Candida albicans and Aspergillus spp. 
The incidence of fungal infections caused by Aspergillus was higher (p < 0.05) in 
patients with hematologic malignancies than in the control group. The independent risk 
factors for fungal infections were fungal colonization, number of antibiotics and duration 
of antibiotic therapy, duration of fever and skin rash. A higher proportion of fungal 
infections was diagnosed on autopsy than during the patients' life (p < 0.01).

70. Janner D, Bork J, Baum M, Chinnock R. Severe pneumonia after heart 
transplantation as a result of human parvovirus B19. J Heart Lung Transplant 1994; 
13:336-338.
Notes : The diverse manifestations of human parvovirus B19 infection have been well 
established. Erythema infectiosum, fetal hydrops, adult arthropathy, and aplastic 
anemia in patients with hemoglobinopathies or underlying immunocompromise have 
been described. Recently we successfully treated a patient who, after heart 
transplantation, had fever, rash, and pneumonia with respiratory failure caused by 
human parovirus B19. Human parovirus B19 has not been reported previously as a 
pathogen causing pulmonary disease after pediatric heart transplantation, and we wish 
to report it at this time.

71. Jantausch BA. Lyme disease, Rocky Mountain spotted fever, ehrlichiosis: 
emerging and established challenges for the clinician. Ann Allergy 1994; 73:4-11; quiz 
11-2.
Notes : OBJECTIVE: The goal of this review is to facilitate the management of patients 
with tick-associated diseases. This article will discuss the epidemiology, clinical 
diagnosis, and antimicrobial therapy of Lyme disease, Rocky Mountain spotted fever, 
and ehrlichiosis. DATA SOURCES: References are limited to the English language and 
extend back to the beginning of the twentieth century. The human and veterinary 
literature were reviewed. Sources include computerized databases and bibliographies of 
recent articles and books. STUDY SELECTION: Papers were selected on the basis of 
their timeliness, explanation of important findings by major investigators, extrapolation 
of clinical data from large patient populations, and clarification of controversial issues. 
Approximately 50 of the articles initially reviewed are included in the bibliography. 
RESULTS: Standardization of laboratory testing for Lyme disease should facilitate 
more accurate diagnosis in the future. Clinical diagnosis of Rocky Mountain spotted 
fever and ehrlichiosis prior to laboratory confirmation is necessary in order to ensure 
timely institution of antimicrobial therapy. CONCLUSIONS: Knowledge of endemic 
regions and seasonal cycles of vectors, varying clinical presentations of disease and 
appropriate utilization of the laboratory are critical for the appropriate diagnosis and 
management of patients with tick-associated diseases.

72. Jayakkody RL, Kottegoda S. Should we continue to use benzathine penicillin for 
rheumatic fever prophylaxis? [see comments]. Ceylon Med J 1993; 38:171-173.

73. Jehn U, Gawaz M, Grunewald R, Hill W, Lorenz B, St"otzer O. Successful 
treatment of patients with hairy cell leukemia (HCL) using a single cycle of 2-chloro-2'-
deoxyadenosine (CdA). Anticancer Res 1993; 13:1809-1814.
Notes : 2-Chloro-deoxyadenosine (CdA) is a new adenosine-deaminase (ADA) resistant 
purine analogue with high specificity for lymphoid cells. It was shown that CdA is very 
effective in hairy cell leukemia (HCL), refractory chronic lymphocytic leukemia and 
cutaneous T-cell lymphoma leading to lasting remissions in the majority of patients 
with HCL. We report the successful treatment of five patients with HCL at different 
stages of their disease using CdA, who were either previously untreated or had received 
interferon, splenectomy and deoxycoformycin (dCF), an ADA-inhibitor with high 
therapeutic efficacy in HCL. After one 7-day course of treatment, all patients reached 
remission. CdA was well tolerated and, only mild side effects such as skin rash, 
headache, fever, nausea were observed. Aplasia was pronounced in all instances with a 
slow recovery. The type of histomorphological procedure in preparing and evaluating 
bone marrow biopsies is emphasized to detect minimal residual infiltration by hairy 
cells.

74. Jones CM, Dunn HG, Thomas EE, Cone RW, Weber JM. Acute encephalopathy 
and status epilepticus associated with human herpes virus 6 infection. Dev Med Child 
Neurol 1994; 36:646-650.
Notes : A previously healthy 22-month-old boy presented in status epilepticus with high 
fever. He was comatose, with upper respiratory-tract infection. The seizures responded 
to anticonvulsant therapy. The boy's temperature returned to normal within 24 hours 
and he recovered slowly from his encephalopathy. On the third hospital day, he 
exhibited the characteristic rash of reseola infantum. Acute infection with human 
herpes virus 6 (HHV-6) was established serologically by enzyme immunoassay. HHV-6 
DNA was not detected by polymerase chain reaction in CSF or serum at the onset of 
illness, but was found three months later in the child's saliva. The pathogenesis of the 
patient's encephalopathy is discussed. It is concluded that HHV-6 infection should be 
considered in infants and young children with febrile status epilepticus.

75. Jorde UP, Horowitz HW, Wormser GP. Utility of dapsone for prophylaxis of 
Pneumocystis carinii pneumonia in trimethoprim-sulfamethoxazole-intolerant, HIV-
infected individuals. AIDS 1993; 7:355-359.
Notes : OBJECTIVE: To determine the safety and efficacy of 100 mg dapsone three 
times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, 
trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients. DESIGN: Retrospective 
chart review of patients followed-up to 22 May 1992. SETTING: Infectious diseases 
outpatient clinic of a tertiary care center in suburban New York City. PATIENTS: 
Twenty-three HIV-infected patients requiring PCP prophylaxis with documented 
intolerance to TMP-SMX. MAIN OUTCOME MEASURES: Patients were followed 
clinically and with laboratory testing at approximately monthly intervals. RESULTS: 
Dapsone was discontinued in nine (39%) patients because of adverse reactions. All 
reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 
14 patients developed histologically proven PCP over 126 patient-months of follow-up. 
CONCLUSION: Approximately 40% of TMP-SMX-intolerant HIV-infected individuals are 
also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 
100 mg dapsone three times weekly. More experience with other dose regimens and 
alternative agents is needed.

76. Jouben LM, Steele RJ, Bono JV. Orthopaedic manifestations of Lyme disease. 
Orthop Rev 1994; 23:395-400.
Notes : Lyme disease is caused by the spirochete Borrelia burgdorferi and is 
transmitted by the Ixodes tick. Early diagnosis is difficult because the tick bite may go 
unnoticed and the distinguishing rash, erythema chronicum migrans, often does not 
occur. Serologic tests are both sensitive and specific in the later stages of the disease 
but not in stage 1. Thus diagnosis of Lyme disease remains clinical. Knowledge of the 
orthopaedic manifestations of Lyme disease may aid in early diagnosis and help 
differentiate from possible cases of juvenile rheumatoid arthritis and septic arthritis. If 
septic arthritis is suspected, appropriate antibiotic therapy should be initiated while 
awaiting serology for Lyme disease. Recurrence of Lyme arthritis following antibiotic 
treatment is rare. Lyme disease should be considered in any patient with arthritis and a 
history of rash, fever, or neurologic or cardiac abnormality.

77. Jundt JW, Creager AH. STAR complexes: febrile illnesses associated with sore 
throat, arthritis, and rash. South Med J 1993; 86:521-528.
Notes : Between January 1990 and February 1991 we evaluated the cases of 20 
patients for a symptom complex consisting of Sore throat, elevated Temperature, 
migratory Arthritis, and a pruritic urticarial Rash (STAR). The patients ranged in age 
from 3 1/2 to 48 years; most were from central Texas. Duration of illness varied from 2 
weeks to longer than 1 year. Results of laboratory studies included the following 
abnormal findings: elevated erythrocyte sedimentation rate, leukocytosis, anemia, and 
thrombocytosis. Eleven of 18 (61%) patients had low antinuclear antibody titers. HLA-
A2 was noted in 8 of 10 (80%) of those tested. Test results were positive in eight cases 
for IgM antibodies to parvovirus and in six cases for IgM antibodies to rubella, 
suggesting that these entities may represent an underdiagnosed cause of STAR 
complex. In six cases no specific cause of disease was found; these cases may be 
attributable to other infectious agent(s) yet to be identified. Here we present a 
description of the cases, a discussion of the differential diagnosis, and an evaluation of 
STAR complex.

78. Kain KC, Schulzer M, Chow AW. Clinical spectrum of nonmenstrual toxic shock 
syndrome (TSS): comparison with menstrual TSS by multivariate discriminant analyses 
[see comments]. Clin Infect Dis 1993; 16:100-106.
Notes : To further characterize the clinical spectrum of nonmenstrual toxic shock 
syndrome (NMTSS), we constrasted and compared the clinical and laboratory features 
of 24 patients with NMTSS with those of 21 patients with menstrual TSS (MTSS), using 
univariate and stepwise discriminant analyses. In contrast to patients with MTSS, 
those with NMTSS comprised a heterogeneous group with varying host factors and 
clinical presentations. The NMTSS group differed from the MTSS group in terms of the 
frequency of prior antimicrobial treatment (46% vs. 16%; P = .05), the rate of 
nosocomial acquisition (65% vs. 0; P = .0001), and the time of onset of fever and rash 
in relation to the initial symptoms (P = .005 and .03, respectively, with earlier onset in 
the NMTSS group). In addition, NMTSS patients experienced more frequent renal and 
CNS complications and less frequent musculoskeletal involvement (P = .07 in all three 
cases). Stepwise discriminant analysis identified four variables (delayed onset of TSS 
symptoms after precipitating injury or event, more frequent CNS manifestations, less 
frequent musculoskeletal involvement, and higher degree of anemia) differentiating 
NMTSS patients from MTSS produced TSS toxin 1 (TSST-1) with comparable 
frequency (62% vs. 84%; P = .2), but production of staphylococcal enterotoxin A (SEA) 
was less common in NMTSS than in MTSS (33% vs. 74%; P = .01). Furthermore, 
MTSS-associated isolates more commonly coexpressed TSST-1 and SEA than did 
NMTSS-associated isolates (68% vs. 28%; P = .01).(ABSTRACT TRUNCATED AT 250 
WORDS).

79. Kanegane H, Ochiai H, Shiraki K. Human herpesvirus 6 as a causal agent of the 
first febrile episode after birth [letter]. Pediatr Infect Dis J 1993; 12:171-172.

80. Kar SK, Patnaik S, Kumaraswami V, Murty RS. Side reactions following ivermectin 
therapy in high density bancroftian microfilaraemics. Acta Trop 1993; 55:21-31.
Notes : Side reactions following ivermectin treatment were evaluated in sixty males with 
high density bancroftian microfilaremia (GM 1388/ml). Following a single oral dose of 
ivermectin of different strengths (20, 50, 100 or 200 micrograms/kg), microfilariae 
clearance and side reactions were monitored in a double blind fashion. Microfilaria 
levels fell rapidly after ivermectin administration in all dosage groups and 98% of 
pretreatment microfilariae was cleared after 12 h of treatment. The rate of microfilaria 
(mf) clearance was slower with 20 micrograms/kg than with the highest dose (200 
micrograms/kg) administered. Forty-six patients (77%) became amicrofilaraemic within 
2 weeks of treatment. Side reactions were noted in 97% of cases. The most common 
reactions were fever, headache, weakness, myalgia and cough which appeared by 12 h 
and subsided by 72 h following treatment. The frequency and intensity of side reactions 
were related to pretreatment mf densities and were independent of the dose 
administered. Unusual side reactions were noted in a few patients with high density 
microfilaraemia. These included intense cough, shortness of breath, blood tinged 
mucoid expectoration associated with patchy pneumonitis of the lung. Itchy rashes, 
lymphatic nodules and raised alkaline phosphatase level were also observed in some 
patients. These side reactions were transient, self limiting and were not serious enough 
to warrant any treatment. These exaggerated unusual reactions were possibly due to 
allergic response of the susceptible host to rapid killing of large number of microfilariae.

81. Karras DJ. Severe low back pain secondary to acute interstitial nephritis following 
administration of ranitidine. Am J Emerg Med 1994; 12:67-68.
Notes : Acute interstitial nephritis is a disease characterized by renal inflammation and 
is thought to be secondary to a hypersensitivity reaction. Although the causes of acute 
interstitial nephritis are numerous, adverse reactions to many common drugs, 
particularly antibiotics and nonsteroidal anti-inflammatory agents, are important 
etiological factors. Acute interstitial nephritis has many clinical manifestations, most 
notably fever and rash. Flank pain is an uncommon presentation. A case of acute, 
severe, low-back pain and rash in a healthy woman found to be secondary to acute 
interstitial nephritis is reported. The etiology of acute interstitial nephritis in this 
patient's case is suspected to be ranitidine (Zantac; Glaxo Pharmaceuticals, Research 
Triangle Park, NC), which has not been previously associated with this syndrome.

82. Katoh S, Terashima S, Nakahara Y, Yamada H, Tatsukawa H, Ida K, et al. 
Hypersensitivity to heparin; a case report. Nippon Jinzo Gakkai Shi 1993; 35:411-414.
Notes : Hypersensitivity reactions to heparin are very rare. A generalized 
hypersensitivity reaction including as fever and skin rash to a porcine- and bovine-
derived heparin preparation was observed in a hemodialysis patient due to the nephrotic 
syndrome. The patient revealed peripheral eosinophilia and normal serum IgE. The 
results of a drug lymphocyte stimulating test on heparin were positive. Following 
prednisolone administration and infusion of nafamostat mesilate as anticoagulant 
therapy during hemodialysis, the high fever and generalized urticaria disappeared. 
Caution is required when conducting heparin therapy on hemodialysis patients.

83. Katz DA, Berger JR, Duncan RC. Neurosyphilis. A comparative study of the effects 
of infection with human immunodeficiency virus [published erratum appears in Arch 
Neurol 1993 Jun;50(6):614]. Arch Neurol 1993; 50:243-249.
Notes : BACKGROUND--The course of neurosyphilis has been reported to be altered 
by human immunodeficiency virus (HIV) infection. Prior reports of neurosyphilis 
occurring in association with HIV infection have been largely anecdotal and have failed 
to compare neurosyphilis in patients with HIV infection with an uninfected control group. 
This study was performed to determine if the clinical presentation encountered is 
different in the presence of HIV infection. DESIGN--A retrospective, hospital-based, 
case series study based on chart review encompassing a 64-month period. SETTING--
The study was performed in a large, university-affiliated, public health trust hospital in 
south Florida. PATIENTS--Forty-six hospitalized patients with neurosyphilis were 
identified; 13 patients fulfilled Centers for Disease Control and Prevention (Atlanta, Ga) 
criteria for acquired immunodeficiency syndrome (AIDS), 11 were HIV seropositive only, 
and 22 were HIV uninfected. Neurosyphilis was determined by a reactive cerebrospinal 
fluid VDRL slide test. RESULTS--The HIV-infected patients (both AIDS and HIV-
seropositive groups) were younger and more frequently had features of secondary 
syphilis, such as rash, fever, adenopathy, headache, or meningismus. Significant 
differences were observed in cerebrospinal fluid measurements when the HIV-infected 
group was compared with the HIV-uninfected group, including a higher mean white 
blood cell count in patients with AIDS and a higher mean protein level and a lower 
mean glucose level in the HIV-infected group. Syphilitic meningitis was more common 
in HIV-seropositive patients, although the HIV-uninfected patients presented with a 
greater variety of types of neurosyphilis. Ophthalmic syphilis was observed more 
frequently in the HIV-infected group. CONCLUSIONS--Significant differences exist 
between neurosyphilis occurring in the presence and absence of HIV infection.

84. Kaufmann D, Pichler W, Beer JH. Severe episode of high fever with rash, 
lymphadenopathy, neutropenia, and eosinophilia after minocycline therapy for acne. 
Arch Intern Med 1994; 154:1983-1984.
Notes : Minocycline is a tetracycline agent frequently used for acne therapy. It has a 
few rare but severe side effects that are not widely known but should be recognized 
early as drug related. These include acute hepatitis and liver failure; a Loffler-like 
syndrome with pulmonary infiltrates, wheezing, fever, and eosinophilia; skin eruptions, 
eosinophilic cellulitis, and pustular folliculitis with eosinophilia; and a lupuslike 
syndrome. Side effects that are better known and recognized include 
photosensitization, skin exanthema with pruritus, and pseudotumor cerebri.

85. Keet IP, Krijnen P, Koot M, Lange JM, Miedema F, Goudsmit J, et al. Predictors of 
rapid progression to AIDS in HIV-1 seroconverters. AIDS 1993; 7:51-57.
Notes : OBJECTIVE: To determine whether at the time of HIV-1 seroconversion rapid 
progressors to AIDS and a low CD4+ count can be distinguished by the clinical 
presentation of primary HIV-1 infection and serological and immunological 
characteristics. DESIGN: Prospective cohort study on HIV-1 infection in homosexual 
men. SETTING: The Municipal Health Service, Amsterdam, The Netherlands. 
SUBJECTS: One hundred and eight men who seroconverted for HIV-1 during follow-up. 
MAIN OUTCOME MEASURES: Progression to AIDS and progression to a CD4+ 
lymphocyte count < 200 x 10(6)/l. RESULTS: Symptomatic primary HIV infection with 
fever and skin rash, absence of anti-HIV core and transient HIV p24 antigenemia were 
independent predictors of progression to AIDS at the time of HIV-1 seroconversion. A 
low CD4+ count immediately after seroconversion and the calendar year were 
independent predictors of progression to a low CD4+ count at the time of HIV-1 
seroconversion. CONCLUSIONS: Even in the earliest stage of HIV-1 infection a small 
group of individuals at high risk for rapid progression to AIDS can be recognized by the 
clinical presentation of primary HIV infection, the presence of HIV p24 antigenaemia 
and the absence of a serological response to HIV core protein.

86. Kennedy CA, Pimentel JA, Lewis DE, Anderson MD, Weiss PJ, Oldfield EC, 3d. 

Crossover of human immunodeficiency virus-infected patients from aerosolized 
pentamidine to trimethoprim-sulfamethoxazole: lack of hematologic toxicity and 
relationship of side effects to CD4+ lymphocyte count. J Infect Dis 1993; 168:314-317.
Notes : Trimethoprim-sulfamethoxazole (TMP/SMZ) was given in a crossover study to 
130 human immunodeficiency virus-infected patients who had been receiving 
aerosolized pentamidine; 86 (66%) successfully crossed over to TMP/SMZ without 
hypersensitivity reactions or hematologic toxicity. No significant changes occurred in 
mean hemoglobin concentration, leukocyte count, or platelet count between study 
enrollment and 12-month follow-up. Predominant side-effects, in 41 patients (33.8%), 
were fever and maculopapular rashes, which resolved promptly with discontinuation of 
TMP/SMZ. The mean time to first side effect was 12.3 days, and 86% of side effects 
developed within 30 days. Three patients experienced toxicity serious enough to 
warrant hospitalization. Of patients with < or = 200 CD4+ lymphocytes/mm3, 57% 
developed rashes after the cross-over compared with only 27% of patients with higher 
CD4+ cell counts. Many patients currently receiving aerosolized pentamidine can be 
safely crossed over without hematologic toxicity or hypersensitivity reactions.

87. Kirkland KB, Marcom PK, Sexton DJ, Dumler JS, Walker DH. Rocky Mountain 
spotted fever complicated by gangrene: report of six cases and review. Clin Infect Dis 
1993; 16:629-634.
Notes : Although mortality due to fulminant Rocky Mountain spotted fever (RMSF) is 
well appreciated, the ability of the disease to cause survivors to become permanently 
disabled is not as widely known. We report six cases of RMSF complicated by 
gangrene. Although four patients required multiple limb and/or digital amputations, only 
one death resulted. Our review of the English-language literature revealed 23 additional 
cases of RMSF complicated by gangrene. Pathophysiologically, gangrene is most 
likely related to small-vessel occlusion. Skin necrosis and gangrene in association with 
RMSF are the extreme end on a continuum from reversible to irreversible skin and 
tissue damage caused by Rickettsia rickettsii. Most patients with RMSF have a typical 
skin rash that resolves without sequelae. Some patients develop minute cicatrices 
marking the location of focal cutaneous necrosis; for other patients, digital ischemia 
occurs transiently or evolves to produce severe ischemic changes without gangrene 
that result in permanent impairment. At the far end of this clinical continuum are 
patients who develop gangrene requiring amputation.

88. Kirkland KB, Wilkinson WE, Sexton DJ. Therapeutic delay and mortality in cases 
of Rocky Mountain spotted fever. Clin Infect Dis 1995; 20:1118-1121.
Notes : We conducted a retrospective cohort study of patients with Rocky Mountain 
spotted fever (RMSF) at a university hospital in order to assess the relationship 
between delay in treatment and mortality and to identify predictors of delay in initiating 
therapy. Patients with RMSF who received antirickettsial therapy within 5 days of the 
onset of symptoms were significantly less likely to die than were those who received 
treatment after the 5th day of illness (6.5% vs. 22.9%, respectively; P < .03). Ninety 
percent of patients were seen by a physician during this 5-day period, yet less than 
one-half of them received treatment before day 6. Three factors were independent 
predictors of failure by the physician to initiate therapy the first time a patient was 
seen: absence of a rash, presentation between 1 August and 30 April, and presentation 
within the first 3 days of illness. Until reliable early diagnostic tests become available, 
physicians may be able to decrease the mortality associated with RMSF by instituting 
empirical treatment of suspected cases within the first 5 days of illness.

89. Klein MR, Keet IP, D'Amaro J, Bende RJ, Hekman A, Mesman B, et al. 
Associations between HLA frequencies and pathogenic features of human 
immunodeficiency virus type 1 infection in seroconverters from the Amsterdam cohort of 
homosexual men. J Infect Dis 1994; 169:1244-1249.
Notes : HLA-disease associations may be important for understanding the 
pathogenesis of human immunodeficiency virus type 1 (HIV-1) infection. Therefore, 106 
homosexual men from the Amsterdam Cohort Study on AIDS with a known date of HIV-
1 seroconversion were serologically typed for HLA. Several significant associations 
between HLA type and pathogenic features of HIV-1 infection were observed: Subjects 
with fever and skin rash during primary HIV-1 infection showed an increased frequency 
of HLA-B62 (relative risk [RR], 5.8; P = .005). The frequency of HLA-B35 was increased 
in subjects with a rapid decline in CD4+ T lymphocytes (RR, 3.2; P = .021). Kaplan-
Meier survival analysis revealed a significant association between HLA-B35 and a 
decrease in CD4+ cells to < 200/microL (P = .01). The strongest association was found 
between HLA-DR1 and AIDS-related Kaposi's sarcoma (RR, 22.5; P < .001), also 
confirmed in survival analysis (P = .001). In AIDS patients with only opportunistic 
infections, increased frequencies of HLA-DR3 (P = .011) and -DQ2 (P = .007) were 
observed. Finally, the occurrence of syncytium-inducing HIV-1 variants was significantly 
associated with HLA-DQ2 (P = .01).

90. Kobune F, Funatu M, Takahashi H, Fukushima M, Kawamoto A, Iizuka S, et al. 
Characterization of measles viruses isolated after measles vaccination. Vaccine 1995; 
13:370-372.
Notes : Seven measles virus (MV) strains were isolated from children who developed 

clinical signs of fever and rash 3-9 days after measles vaccination. The nucleotide 
sequence of the H gene, the molecular size of the H protein, the haemadsorption 
activity on African green monkey red blood cells, and antigenicity as determined by 
virus neutralization revealed that one strain was of the vaccine type and the remaining 
six were the wild virus type. Isolation of the virus directly from patients suspected of a 
vaccine-induced side-reaction and subsequent characterization of such isolated virus 
may be useful in differentiation between vaccine-induced side-reactions and natural 
measles.

91. Kolk A, Horneff G, Wilgenbus KK, Wahn V, Gerharz CD. Acute lethal necrotising 
pancreatitis in childhood systemic lupus erythematosus--possible toxicity of 
immunosuppressive therapy. Clin Exp Rheumatol 1995; 13:399-403.
Notes : We report on a 16 year old girl with a three-year history of systemic lupus 
erythematosus who developed a case of acute lethal haemorrhagic pancreatitis. She 
presented with high grade fever, skin rash, malaise, and arthralgias. Laboratory lupus 
activity parameters were markedly elevated. In the absence of renal, pulmonary, 
cardiac or cerebral involvement, our patient developed pancreatitis leading to 
pancreatogenic shock. Until 14 days before the onset of pancreatitis, the patient's 
medications included prednisolone, azathioprine and methotrexate. At autopsy, no 
autoimmune vasculitis was found in the affected pancreatic tissue. Therefore, an 
etiologic role of combination therapy had to be considered. Whereas methotrexate has 
never been reported to be linked to pancreatitis, a few publications describing 
prednisolone and azathioprine in connection with pancreatitis do exist. Thus, if 
pancreatitis is not just termed idiopathic, it must be attributed to a combination 
regimen of drugs including methotrexate. A review of the literature shows that 
pancreatitis in SLE is rare and has never been associated with methotrexate therapy 
before.

92. Komatsuda A, Chubachi A, Miura AB. Virus-associated hemophagocytic syndrome 
due to measles accompanied by acute respiratory failure. Intern Med 1995; 34:203-206.
Notes : An 18-year-old male who was admitted to hospital due to fever, skin rashes, 
cough, and malaise showed laboratory examination findings of leukopenia, 
thrombocytopenia, mild liver dysfunction, and hypoxia. Bone marrow aspiration revealed 
2% histiocytes with hemophagocytosis. Chest X-ray showed bilateral diffuse interstitial 
pneumonia. The titer of anti-measles virus antibody was < 1:4, and that at 
convalescence stage was 1:64. He was diagnosed as having hemophagocytic 
syndrome and acute respiratory failure due to measles, and was treated with 
methylprednisolone pulse therapy. He promptly recovered from thrombocytopenia and 
acute respiratory distress. Steroid pulse therapy may be effective in these conditions 
due to measles.

93. Korppi M, Tenhola S, Hollmen A. Mucha-Habermann disease: a diagnostic 
possibility for prolonged fever associated with systemic and skin symptoms. Acta 
Paediatr 1993; 82:627-629.
Notes : The severe form of Mucha-Habermann disease with systemic symptoms is a 
rarely diagnosed disease which should be considered for children with prolonged fever, 
impaired general condition, skin manifestations and elevated C-reactive protein 
concentration and/or erythrocyte sedimentation rate. Eleven cases have been 
described previously in children. We describe two acute episodes of this syndrome in a 
three-year-old child; the diagnosis was based on clinical, dermatological and 
histological findings. During both episodes, the fever lasted for more than one week, C-
reactive protein concentration increased to more than 150 mg/l, and there was 
extensive lymph node enlargement. Skin eruption was initially maculopapulous, then 
vesiculous and finally pustulous. On skin biopsy, vasculitic changes were observed. 
We treated the second attack of our patient with high-dose gamma globulin; the first 
attack appeared to resolve itself spontaneously.

94. Koselj M, Kveder R, Bren AF, Rott T. Acute renal failure in patients with drug-
induced acute interstitial nephritis. Ren Fail 1993; 15:69-72.
Notes : The clinical features, laboratory evaluation, and outcome were analyzed in 23 
patients with acute renal failure (ARF) and drug-induced acute interstitial nephritis (21 
proven with biopsy). The groups of drugs implicated were: antibiotics (20 cases), 
nonsteroidal anti-inflammatory drugs (2 cases), and other drugs (phenobarbitone, 1 
case). The clinical and laboratory signs of the disease appeared 3 to 28 days after 
exposure to the drug. Fever, skin rash, and flank tenderness were the most common 
clinical features observed (87%); and hematuria (100%), sterile pyuria (83%), and 
eosinophilia (39%) were established by laboratory tests. Hemodialysis (HD) was 
performed in 7 patients. Complete normalization of kidney function was observed in 3 
patients; improvement to basal level in 3 patients (this group had preexisting renal 
disease); and CRF, requiring HD, in 1 patient. Renal function improved in all patients 
with mild to moderate renal insufficiency regardless of the therapy involved. Statistical 
evaluation could not confirm any significant differences between status of renal function 
at presentation, treatment (corticosteroids versus symptomatic and supportive 
measures only), and outcome of drug-induced acute interstitial nephritis (AIN). In 
summary, ARF due to drug-induced AIN has a favorable course with good prognosis 
regardless of the use or nonuse of corticosteroids in management strategy.

95. Kwong T, Valderrama E, Paley C, Ilowite N. Systemic necrotizing vasculitis 
associated with childhood sarcoidosis. Semin Arthritis Rheum 1994; 23:388-395.
Notes : Childhood sarcoidosis is a rare disorder with protean manifestations. The case 
of a child with prolonged fever, hepatosplenomegaly, pancytopenia, and systemic 
necrotizing vasculitis manifesting as fever, rash and skin infarctions, digital 
pregangrene, and foot drop is reported. This is the first case of systemic necrotizing 
vasculitis reported in sarcoidosis. The fulminant course of the disease required 
treatment with intravenous pulsed cyclophosphamide and high doses of corticosteroids. 
The spectrum of vasculitis in childhood and adult sarcoidosis is reviewed.

96. Lantz B, Cochat P, Bouchet JL, Fischbach M. Short-term niflumic-acid-induced 
acute renal failure in children. Nephrol Dial Transplant 1994; 9:1234-1239.
Notes : Several reports emphasize the adverse effects of non-steroidal anti-
inflammatory drugs (NSAIDs) on renal function. We have observed over the last 10 
years seven cases of acute renal failure (ARF) due to immune interstitial nephritis in 
children. A recommended oral or rectal dose of niflumic acid was prescribed for ear-
nose-throat disorders. Length of exposure was 1-5 days. Clinical symptoms (oedema, 
oliguria or anuria) appeared between 3 and 6 days. Three patients had previously 
received the drug. Hypersensitivity signs (fever, skin rash, eosinophilia, and/or 
increased IgE) were present in all cases, leukocyturia in five cases, and haematuria in 
six cases. Renal biopsy showed interstitial lesions with lymphocyte, eosinophil, and 
plasma cell infiltrates without tubular cell necrosis. Glomeruli were normal on light-
microscopy, except in one patient. Electron-microscopy showed extensive podocyte 
fusion in two patients, who had clinical and laboratory evidence of nephrotic syndrome 
(NS). ARF rapidly disappeared after NSAID withdrawal, except in two patients whose 
renal failure was irreversible despite methylprednisolone bolus. ARF is very rare in 
children treated with niflumic acid. When ARF occurs, different pathophysiological 
mechanisms are involved but the most common is immunological.

97. Lee CK, Gingrich RD, Hohl RJ, Ajram KA. Engraftment syndrome in autologous 
bone marrow and peripheral stem cell transplantation. Bone Marrow Transplant 1995; 
16:175-182.
Notes : Reproducible and characteristic clinical findings of fever, skin rash, capillary 
leak and pulmonary infiltrates have been observed during engraftment in patients with 
autologous bone marrow (BM) and/or peripheral stem cell transplantation (PSCT). Two 
hundred and forty-eight patients were analyzed retrospectively to establish the clinical 
entity, to characterize the clinical course, and to find clinical variables affecting the 
incidence of the syndrome. One hundred and eight cases (83.7 +/- 9.4%) of fevers 
occurring in the periengraftment period (PEN) not associated with positive cultures, 
biopsies, or clinical signs of infection did not reveal delayed documentation of 
concealed infection in 2 weeks after engraftment. Capillary leak, pulmonary infiltrates, 
hypoxia, non-infectious neutropenic fever of engraftment and skin rash were found to be 
interrelated (all P < 0.01 except for hypoxia vs rash; P < 0.05). By stepwise 
discriminant analysis, one hundred and thirty-two patients (58.9 +/- 6.4%) were shown 
to have both skin rash and non-infectious neutropenic fever, thereby constituting the 
syndrome. Sepsis in the first week of neutropenia decreased the incidence of the 
syndrome (58.5 +/- 7.7% with sepsis, 89.6 +/- 4.7% without sepsis, P < 0.01). Post-
transplant granulocyte colony-stimulating factor increased the incidence of the 
syndrome (79 +/- 4.6% with G-CSF vs 48.3 +/- 8.2% without G-CSF, P < 0.01). In bone 
marrow transplantation (BMT), the median time of onset of the syndrome was 7 days 
(range 4-22 days) post-transplant with a median duration of 11 days (range 4-28 days) 
of the initial phase. Thirty-nine patients (17.4 +/- 5.0%) revealed a recurrent pattern 
during the 5th week post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS).

98. Lehman TJ. A practical guide to systemic lupus erythematosus. Pediatr Clin North 
Am 1995; 42:1223-1238.
Notes : Systemic lupus erythematosus is a challenging disease with varied 
manifestations resulting from widespread immune complex deposition. It may present 
in the general pediatric office as an acute illness with fever, rash, and hematuria, or as 
chronic fatigue and malaise that might be mistaken for "school phobia". Although SLE 
remains an infrequent disease in general pediatric practice, mild cases are more 
frequent than was previously recognized. These children benefit from therapy if the 
physician is alert to their occurrence and makes the appropriate diagnosis. The 
understanding of the role of genetics and environmental agents in the pathogenesis of 
SLE has improved over the past 10 years. In addition, the past 10 years have seen 
refinements in the use of immunosuppressive regimens, such as cyclophosphamide, 
that have led to both improved quality of life and improved survival for children with active 
SLE unresponsive to corticosteroids. Although long-term concerns regarding the safety 
and efficacy of immunosuppressive drug regimens persist, the future is increasingly 
bright for children with SLE who receive appropriate care in a timely fashion.

99. Levin S, Goodman LJ. An approach to acute fever and rash (AFR) in the adult. Curr 
Clin Top Infect Dis 1995; 15:19-75.

100. Lew MA, Kehoe K, Ritz J, Antman KH, Nadler L, Kalish LA, et al. Ciprofloxacin 
versus trimethoprim/sulfamethoxazole for prophylaxis of bacterial infections in bone 
marrow transplant recipients: a randomized, controlled trial. J Clin Oncol 1995; 13:239-
250.
Notes : PURPOSE: To compare the efficacy and safety of ciprofloxacin (CIP) and 
trimethoprim/sulfamethoxazole (TMS) for the prevention of bacterial infections in 
patients who received bone marrow transplantation (BMT) for the treatment of solid and 
hematopoietic neoplasms. PATIENTS AND METHODS: Adult inpatients about to 
undergo BMT for lymphoma, leukemia, or solid tumors were enrolled onto a 
prospective, randomized, double-blinded, controlled trial that compared CIP (750 mg 
orally twice per day) with TMS (160 mg trimethoprim and 800 mg sulfamethoxazole 
orally twice per day). Subjects were stratified before randomization according to tumor 
and BMT type. Prophylaxis was begun within 96 hours of initiation of the BMT 
preparative regimen and continued until the onset of fever, signs or symptoms of 
infection, serious adverse effects, or recovery of the absolute granulocyte count (AGC) 
to > or = to 400/microL. RESULTS: Seventy-five CIP recipients and 71 TMS recipients 
were assessable for efficacy. No difference was noted between the two groups in 
occurrence of fever during neutropenia, time to onset of first fever, or overall infection 
rates. Ten bacteremias occurred in CIP recipients versus six in TMS recipients (P = 
.43). Ten episodes of Clostridium difficile enterocolitis occurred in TMS recipients 
versus no episodes in CIP recipients (P = .001). Four infections caused by gram-
negative bacilli, including one bacteremia, occurred in TMS recipients versus none in 
CIP recipients (P = .06). No differences were noted in the incidence of rash or organ 
toxicity. TMS recipients had longer durations of granulocytopenia at AGC levels < or = 
to 500/microL and < or = to 100/microL than did CIP recipients (P = .08 for both 
comparisons). Mean peak and trough serum levels of CIP decreased significantly 
between weeks 1 and 2 of prophylaxis. CONCLUSION: CIP and TMS were equally safe 
and effective in the prevention of bacterial infections in BMT patients when the overall 
infection rate was used as the principal end point. TMS prophylaxis was associated 
with a higher incidence of C difficile enterocolitis and infections caused by gram-
negative bacilli, as well as a trend toward prolongation of granulocytopenia.

101. Lim AG, Hine KR. Fever, vasculitic rash, arthritis, pericarditis, and pericardial 
effusion after mesalazine [see comments]. BMJ 1994; 308:113

102. Lopez KD, Guinan EC. GM-CSF clinical trials: pediatric aplastic anemia and 
Fanconi's anemia. Pediatr Nurs 1995; 21:345-349.
Notes : Two clinical trials were undertaken to evaluate the effect of human recombinant 
granulocyte-macrophage colony stimulating factor (GM-CSF) in pancytopenic pediatric 
patients with aplastic anemia and Fanconi's anemia. In the aplastic anemia trial, 9 out 
of 12 patients had some improvement when treated with GM-CSF. In the Fanconi's 
anemia trial, 6 of 7 patients showed some improvement when treated with GM-CSF. 
For both groups, improvement in white blood cell count and absolute neutrophil count 
were the most common response. Side effects observed during these studies were 
fever, rash, urticaria, and flu-like symptoms. Nursing care of both groups focused on the 
effects of pancytopenia, as well as the potential adverse effects of GM-CSF. Patient 
education focused on teaching drug preparation and storage, subcutaneous injection, 
and potential side effects.

103. Loubser MD, Davies VA, Meyers KE, Christianson AL. Severe illness caused by 
Rickettsia conorii. Ann Trop Paediatr 1993; 13:277-280.
Notes : An 18-month-old boy presented with a 5-day history of lethargy, fever, vomiting 
and rash. He required intensive care for inotropic and ventilatory support. He developed 
a disseminated intravascular coagulopathy and gangrene of his extremities. In addition, 
he had severe neurological dysfunction and loss of vision, both of which recovered 
spontaneously with time. The potential severity of tick typhus caused by Rickettsia 
conorii is described as well as the importance of paired serological tests in the 
diagnosis of this condition.

104. Loveday C, Bingham JS. Changes in circulating immune complexes during the 
Jarisch Herxheimer reaction in secondary syphilis. Eur J Clin Microbiol Infect Dis 1993; 
12:185-191.
Notes : A cohort of 16 patients with early secondary syphilis were recruited to 
investigate the role of circulating immune complexes in the pathogenesis of the Jarisch 
Herxheimer reaction. Eleven of 16 patients had a reaction (68.75%) following initial 
therapy, characterised by rash potentiation, pyrexia, cardiovascular changes and a 
number of less specific symptoms. Circulating immune complexes were measured by 
a standard polyethylene glycol precipitation method and a new sensitive conglutinin 
binding assay that measured the proportion of IgG, IgM and IgA in complexes, in the 
first 8 hours after initial therapy. In the latter assay, resting levels of IgG (range 46-700 
micrograms/ml) and IgM (range 100-410 micrograms/ml) containing complexes were 
raised in all patients prior to treatment, but levels were not predictive of those who 
subsequently had a Jarisch Herxheimer reaction. All patients having a reaction 
demonstrated a mean fourfold or greater rise in IgG (mean rise 712 micrograms/ml; 
range 180-1506 micrograms/ml) and IgM (mean rise 804 micrograms/ml; range 200-
1120 micrograms/ml) containing complexes between two and eight hours after initial 
therapy. No such effect was seen in the five patients having no reaction or in a control 
subject. All these results were confirmed using the polyethylene glycol precipitation 

method for complex detection.

105. Ludwig GV, Iacono-Connors LC. Insect-transmitted vertebrate viruses: flaviviridae. 
In Vitro Cell Dev Biol Anim 1993; 29A:296-309.
Notes : The Flaviviridae include almost 70 viruses, nearly half of which have been 

associated with human disease. These viruses are among the most important 
arthropod-borne viruses worldwide and include dengue, yellow fever, and Japanese 
encephalitis viruses. Morbidity and mortality caused by these viruses vary, but 
collectively they account for millions of encephalitis, hemorrhagic fever, arthralgia, rash, 
and fever cases per year. Most of the members of this family are transmitted between 
vertebrate hosts by arthropod vectors, most commonly mosquitoes or ticks. 
Transmission cycles can be simple or complex depending on the hosts, vectors, the 
virus, and the environmental factors affecting both hosts and viruses. Replication of 
virus in invertebrate hosts does not seem to result in any significant pathology, which 
suggests a close evolutionary relationship between virus and vector. Another example 
of this relationship is the ability of these viruses to grow in invertebrate cell culture, 
where replication usually results in a steady state, persistent infection, often without 
cytopathic effect. Yields of virus from insect cell culture vary but are generally similar to 
yields in vertebrate cells. Replication kinetics are comparable between insect and 
vertebrate cell lines, despite differences in incubation temperature. Both vertebrate and 
insect cell culture systems continue to play a significant role in flavivirus isolation and 
the diagnosis of disease caused by these agents. Additionally, these culture systems 
permit the study of flavivirus attachment, penetration, replication, and release from cells 
and have been instrumental in the production and characterization of live-attenuated 
vaccines. Both vertebrate and insect cell culture systems will continue to play a 
significant role in basic and applied flavivirus research in the future.

106. Madigan JE, Richter PJ, Jr., Kimsey RB, Barlough JE, Bakken JS, Dumler JS. 
Transmission and passage in horses of the agent of human granulocytic ehrlichiosis. J 
Infect Dis 1995; 172:1141-1144.
Notes : The human granulocytotropic ehrlichia and Ehrlichia equi produce similar 
diseases in their respective host species (humans, horses). Currently, the phylogenetic 
and biologic relationships of these 2 uncultured pathogens remain unclear. Previous 
studies have revealed nucleotide sequence similarity approaching identity at the level of 
the 16S ribosomal RNA gene. To investigate the biologic similarities of these 2 
ehrlichiae, the susceptibility of horses to the human agent was tested by intravenous 
inoculation of infected human blood. The results demonstrate that the human 
granulocytotropic ehrlichia produces a disease in the horse indistinguishable from that 
caused by E. equi, providing biologic evidence that these 2 organisms are highly 
related and potentially conspecific. It is possible that cases of human illness now 
attributed to human granulocytotropic ehrlichia may in fact be caused by 1 or more 
strains of an ehrlichia known chiefly as an equine pathogen.

107. Magnarelli LA, Stafford KC, 3rd, Mather TN, Yeh MT, Horn KD, Dumler JS. 
Hemocytic rickettsia-like organisms in ticks: serologic reactivity with antisera to 
Ehrlichiae and detection of DNA of agent of human granulocytic ehrlichiosis by PCR. J 
Clin Microbiol 1995; 33:2710-2714.
Notes : Ixodid ticks were collected from Connecticut, Massachusetts, Missouri, 
Pennsylvania, Rhode Island, and British Columbia (Canada) during 1991 to 1994 to 
determine the prevalence of infection with hemocytic (blood cell), rickettsia-like 
organisms. Hemolymph obtained from these ticks was analyzed by direct and indirect 
fluorescent antibody (FA) staining methods with dog, horse, or human sera containing 
antibodies to Ehrlichia canis, Ehrlichia equi, or Rickettsia rickettsii. Of the 693 nymphal 
and adult Amblyomma americanum, Dermacentor variabilis, Ixodes scapularis, and 
Ixodes pacificus ticks tested with dog anti-E. canis antiserum, 209 (32.5 ) contained 
hemocytic bacteria. The prevalence of infected ticks varied greatly with species and 
locale. In parallel tests of duplicate hemolymph preparations from adult I. scapularis 
ticks, the hemocytic organisms reacted positively with E. canis and/or E. equi antisera, 
including sera from persons who had granulocytic ehrlichiosis. In separate PCR 
analyses, DNA of the agent of human granulocytic ehrlichiosis was detected in 59 
(50.0 ) of 118 adult and in 1 of 2 nymphal I. scapularis ticks tested from Connecticut. 
There was no evidence of Ehrlichia chaffeensis DNA in these ticks. In indirect FA tests 
of hemolymph for spotted fever group rickettsiae, the overall prevalence of infection was 
less than 4 . Specificity tests of antigens and antisera used in these studies revealed 
no cross-reactivity between E. canis and E. equi or between any of the ehrlichial 
reagents and those of R. rickettsii. The geographic distribution of hemocytic 
microorganisms with shared antigens to Ehrlichia species or spotted fever group 
rickettsiae is widespread.

108. Malheiros SM, Oliveira AS, Schmidt B, Lima JG, Gabbai AA. Dengue. Muscle 
biopsy findings in 15 patients. Arq Neuropsiquiatr 1993; 51:159-164.
Notes : Dengue is known to produce a syndrome involving muscles, tendons and joints. 
The hallmark of this syndrome is severe myalgia but includes fever, cutaneous rash, 
and headache. The neuromuscular aspects of this infection are outlined only in isolated 
reports, and the muscle histopathological features during myalgia have not been 
described. In order to ascertain the actual neuromuscular involvement in dengue and 
better comprehend the histological nature of myalgia, we performed a clinical and 
neurological evaluation, a serum CPK level and a muscle biopsy (with histochemistry) 
in 15 patients (4 males), median age 23 years (range 14-47) with classic dengue fever, 
serologically confirmed, during the brazilian dengue epidemics from September 1986 to 
March 1987. All patients had a history of fever, headache and severe myalgia. Upon 
examination 4 had a cutaneous rash, 3 had fever, and 3 a small hepatomegaly. The 
neurological examination was unremarkable in all and included a manual muscle test. 
CPK was mildly elevated in only 3 patients. Muscle biopsy revealed a light to moderate 
perivascular mononuclear infiltrate in 12 patients and lipid accumulation in 11. Mild 
mitochondrial proliferation was seen in 3, few central nuclei in 3, rare foci of 
myonecrosis in 3, and 2 patients had type grouping. Dengue in our patients, produced 
myalgia but no detectable muscle weakness or other neuromuscular involvement. The 
main histopathological correlation with myalgia seems to be a perivascular 
mononuclear infiltrate and lipid accumulation.

109. Malnick SD, Atali M, Israeli E, Abend Y, Geltner D. 
Trimethoprim/sulfamethoxazole-induced rash, fever, abnormal liver function tests, 
leukopenia, and thrombocytopenia [letter]. Ann Pharmacother 1993; 27:1139-1140.

110. Marschang A, Nothdurft HD, Kumlien S, von Sonnenburg F. Imported rickettsioses 
in German travelers. Infection 1995; 23:94-97.
Notes : Twenty-two cases of rickettsiosis imported to Germany (13 men, nine women, 
average age 42 years) in a 5-year period were analyzed retrospectively regarding the 
travel histories, symptoms and clinical findings, laboratory features and course of the 
disease. The two primary rickettsial diseases were boutonneuse fever (18 patients) and 
scrub typhus (three patients). One patient had murine typhus. The main symptom was 
fever in 91% followed by headache (64%), myalgia (40%), arthralgia (50%) and diarrhea 
(36%). The most frequent clinical finding was lymphadenopathy in 65%. Eschar was 
detectable in 55% of patients with Rickettsia conori infection and in one patient with 
Rickettsia tsutsugamushi infection. All patients with R. tsutsugamushi infection as well 
as 33% of the patients with R. conori infection had a macular exanthema. One patient 
with scrub typhus had pleural and pericardial effusions. Seventy-three percent had an 
increased ESR. Three patients had leucocytosis, three increased transaminases and 
two normochromic anemia. The incubation period for R. conori infection was 5 to 28 
days (average 14 days), for R. tsutsugamushi infection 7 to 21 days (average 16 days). 
Twenty-one patients were treated with tetracycline or doxycycline, one with 
erythromycin. All patients were cured. One patient had a relapse. Due to the fact that 
the symptoms are often not characteristic and that the routine laboratory findings are of 
only marginal help, the diagnosis of rickettsial diseases is often not easy. A detailed 
travel history sometimes gives an important hint for diagnosis.

111. Mevorach D, Perrot S, Buchanan NM, Khamashta M, Laoussadi S, Hughes GR, 
et al. Appearance of systemic lupus erythematosus after thymectomy: four case 
reports and review of the literature. Lupus 1995; 4:33-37.
Notes : The appearance of systemic lupus erythematosus (SLE) after thymectomy (or 
thymomectomy) is presented in four patients together with a comparative review of 
additional reports found in a Medline search for the years 1966-94 in the English and 
French literature. Fourteen women and two men of average age of 39 years (range 11-
66 years) at presentation, developed SLE after thymectomy (11 patients) or 
thymomectomy (five patients). Half developed SLE within 3 years after surgery (range 3 
months to 18 years). The most common SLE manifestation was polyarthritis occurring 
in 15 of 16 patients either at presentation or during the first year. Other frequent 
manifestations included skin rashes, fever, cytopenias and pleuritis. Two rare 
manifestations of SLE, optic neuritis and transverse myelitis, were reported in two 
patients. Thymic hormone activity was measured in one patient and was undetectable 
compared with normal controls. HLA studies in eight patients showed the combination 
of A1, B8 in four. In conclusion, the appearance of SLE after thymectomy or 
thymomectomy appears to be more than a coincidence. It may provide insights into the 
pathogenesis of SLE.

112. Middleton DB. Tick-borne infections. What starts as a tiny bite may have a 
serious outcome. Postgrad Med 1994; 95:131-139.
Notes : Tick-borne illnesses are being reported increasingly often. Unlike Lyme 
disease, which tends to be indolent, Rocky Mountain spotted fever and ehrlichiosis can 
kill and so must be recognized and treated promptly. These diseases require clinical 
diagnosis, because laboratory confirmation with antibody tests takes too long. 
Tetracycline hydrochloride, doxycycline (Doryx, Vibramycin), or chloramphenicol 
(Chloromycetin) treatment is effective. Other diseases (eg, babesiosis, tularemia) are 
encountered occasionally and can also be fatal but are treatable with antibiotics.

113. Moder KG, Miller TD, Allen GL. Cardiac tamponade: an unusual feature of adult 
onset Still's disease. J Rheumatol 1995; 22:180-182.
Notes : Adult onset Still's disease (AOSD) is an uncommon, systemic, inflammatory 
disorder of unknown etiology characterized by the triad of fever, arthritis and rash. We 
describe 2 cases of cardiac tamponade in patients with AOSD, review reported cases, 
and describe the features, and therapy of AOSD.

114. Moreira RC, Castrignano SB, Carmona Rd, C, Gomes FM, Saes SG, Oliveira RS, 
et al. An exanthematic disease epidemic associated with coxsackievirus B3 infection 
in a day care center. Rev Inst Med Trop Sao Paulo 1995; 37:235-238.
Notes : An epidemic of exanthematic illness in a day care center is described. Ten 
children aged 7 to 13 months were affected by the illness. The exanthem was 
characterized by nonconfluent macular or maculopapular lesions that appeared on the 
face, body and limbs. Fifty percent of the infected children had fever of up to 39 degrees 
C at the beginning of the disease. Coxsackievirus B3 (CB3) was isolated from the stool 
of one ill child. Paired serum samples were obtained from eight ill children and six of 
them presented seroconversion to CB3. Antibodies to CB3 were detected at titers 
higher than 16 in a single serum sample collected from the other two patients. 
Neutralizing antibodies to CB3 were detected in 71.0% of the contact children.

115. Murray JL, Cunningham JE, Brewer H, Mujoo K, Zukiwski AA, Podoloff DA, et al. 
Phase I trial of murine monoclonal antibody 14G2a administered by prolonged 
intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol 1994; 
12:184-193.
Notes : PURPOSE: The purpose of this phase I trial was to determine the toxicity and 
maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2) 
in cancer patients. PATIENTS AND METHODS: Following tracer doses of iodine-131-
labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma, 
neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations of 
50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days. RESULTS: 
The overall sensitivity of external immunoscintigraphy was 64 of 74 known metastases 
(86%). Toxicity from prolonged infusion of 14G2a consisted of severe generalized pain, 
hyponatremia, fever, rash, paresthesias, weakness, and chronic refractory postural 
hypotension (two patients). Toxicity was less severe in pediatric patients. The MTD of 
Mab was 100 mg/m2. Sixteen of 18 patients developed human antimouse antibodies 
(HAMA) to 14G2a. Terminal-phase half-life (T1/2) of unlabeled Mab was 6.6 +/- 1.8 
hours for patients receiving 50 mg/m2 and 39.5 +/- 13.3 hours at the 100-mg/m2 level. 
Tumor biopsies from six melanoma patients were positive for GD2 antigen, but only two 
of six had trace amounts of 14G2a present. Three mixed responses (two melanoma, 
one osteosarcoma) and two partial responses (PRs; neuroblastoma) were observed. 
CONCLUSION: Mab 14G2a has modest antitumor activity at the expense of significant 
toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other 
than in pediatric patients with neuroblastoma.

116. Myers SA, Sexton DJ. Dermatologic manifestations of arthropod-borne diseases. 
Infect Dis Clin North Am 1994; 8:689-712.
Notes : The arthropod-borne rickettsial, borrelial, and bacterial diseases of North 
America are a diverse group of disorders that produce a wide variety of cutaneous 
abnormalities. These dermatologic abnormalities are often valuable clinical clues that 
may reveal or suggest the correct diagnosis to the astute clinician. We review the usual 
and unusual dermatologic manifestations of Rocky Mountain spotted fever, murine and 
sylvatic typhus, rickettsialpox, ehrlichiosis, Lyme disease, tick-borne relapsing fever, 
Colorado tick fever, and tularemia. In some of these diseases, skin manifestations may 
be diagnostic; in others, dermatologic findings may be the initial and only clues that 
leads to the initiation of life-saving therapy. In other arthropod-borne infections, the 
appearance or evolution of the skin rash may be characteristic enough to suggest the 
proper diagnosis.

117. Nakajima H, Munakata A, Yoshida Y. Adverse effects of sulfasalazine and 
treatment of ulcerative colitis with mesalazine. J Gastroenterol 1995; 30 Suppl 8:115-
117.
Notes : We investigated the adverse effects of sulfasalazine in the treatment of 
inflammatory bowel disease in Japan. In our first survey, adverse effects were observed 
in 52 out of 751 patients with ulcerative colitis (6.9%) and in 8 out of 221 patients with 
Crohn's disease (3.6%); i.e., such effects were observed in 60 out of 972 patients with 
inflammatory bowel disease. In our second survey, we examined 94 adverse reactions 
in 64 patients with ulcerative colitis. The main adverse reactions were exanthema, fever, 
nausea and vomiting, angioedema, and liver damage, in decreasing order of frequency; 
these reactions accounted for about 80% of the adverse reactions. Most of the 
reactions (62%) occurred within 1 month after the beginning of sulfasalazine intake. 
Mesalazine is thought to effectively release the 5-ASA molecule in the colon and has 
already proven of value in patients with mild active ulcerative colitis. We evaluated the 
effect of mesalazine in patients intolerant to sulfasalazine. Effectiveness was observed 
in 14 out of 18 patients with active ulcerative colitis (78%) and in 3 out of 3 patients in 
the quiescent state. These results suggest that mesalazine is effective for the 
treatment of patients with ulcerative colitis who are intolerant to sulfasalazine; this drug 
could be a gleam of hope to those patients.

118. Nesher G, Osborn TG, Moore TL. Parvovirus infection mimicking systemic lupus 
erythematosus. Semin Arthritis Rheum 1995; 24:297-303.
Notes : There are striking similarities between human parvovirus B19 (HPV-B19) 
infection and systemic lupus erythematosus (SLE): both may present with malar rash, 
fever, arthropathy, myalgia, cytopenia, hypocomplementemia, anti-DNA, and 
antinuclear antibodies (ANA). Therefore, it is difficult at times to differentiate HPV-B19 
infection from SLE presentation or exacerbation. We report 4 cases of HPV-B19 
infection mimicking SLE and review 10 other reported cases, all of whom were women. 
The similarity to a typical SLE presentation was indeed striking: most patients 
presented with rash, arthropathy, myalgia, fever, and positive ANA. In some cases, 
HPV-B19 infection seemed to exacerbate SLE rather then resemble it, and 
differentiation was difficult. Nearly all patients improved within several weeks. However, 
a few patients had symptoms and laboratory abnormalities lasting more than 6 months. 
The possibility of HPV-B19 infection should be entertained in patients presenting with 
SLE-like features.

119. Njoo FL, Hack CE, Oosting J, Stilma JS, Kijlstra A. Neutrophil activation in 
ivermectin-treated onchocerciasis patients. Clin Exp Immunol 1993; 94:330-333.
Notes : Ivermectin is a safe and effective drug for onchocerciasis treatment. In certain 
individuals, however, therapy is accompanied by adverse reactions. The mechanisms 
underlying these reactions are not yet known. The aim of the present study was to 
investigate whether neutrophils are involved in the development of these adverse 
reactions. Elastase and lactoferrin, two markers for the release of neutrophil azurophilic 
and specific granule contents respectively, were measured by radioimmunoassays in 
plasma of onchocerciasis patients with varying degrees of side effects, as well as in 
control subjects before and 1 and 2 days after ivermectin treatment. A considerable 
increase of elastase levels after treatment was observed, whereas lactoferrin levels did 
not change. The percentage of patients with elevated elastase levels was significantly 
correlated with the degree of side effects. These findings suggest that neutrophil 
activation may be involved in the development of adverse reactions in these patients.

120. Okada K, Ueda K, Kusuhara K, Miyazaki C, Tokugawa K, Hirose M, et al. 
Exanthema subitum and human herpesvirus 6 infection: clinical observations in fifty-
seven cases. Pediatr Infect Dis J 1993; 12:204-208.
Notes : Exanthema subitum had been speculated to be a viral disease although its 
pathogen is unknown. Human herpesvirus 6 (HHV-6), first isolated in 1986, was proved 
by Yamanishi et al. to be the causal agent of exanthema subitum. To evaluate the role 
of HHV-6 as the causal agent in clinically diagnosed exanthema subitum, we tested for 
HHV-6 antibody in 57 infants with clinical exanthema subitum and exanthema subitum-
like rash without fever. Of the 53 patients with clinical exanthema subitum 43 showed 
seroconversion or a significant rise in antibody titer to HHV-6, 7 were seropositive 
without significant rise and 3 remained seronegative. The clinical manifestations of 
these 43 infants with serologically confirmed HHV-6 infection were consistent with the 
classical characteristics of exanthema subitum. The 4 patients with atypical 
exanthema subitum showed significant rises in antibody titer. Our results therefore 
show that the majority of cases with typical clinical manifestations of exanthema 
subitum had HHV-6 infection. Most cases with HHV-6 infection had the typical clinical 
course of exanthema subitum, and a few cases might show an afebrile exanthema 
subitum-like rash.

121. Okuda T, Umezawa Y, Ichikawa M, Hirata M, Oh-i T, Koga M. A case of drug 
eruption caused by the crude drug Boi (Sinomenium stem/Sinomeni caulis et 
Rhizoma). J Dermatol 1995; 22:795-800.
Notes : We report a case of drug eruption caused by the crude drug Boi. A 41-year-old 
female patient had been diagnosed with chronic rheumatoid arthritis in the department 
of internal medicine. After ingestion of a decoction of the crude drug Boi for the 
alleviation of arthralgia, a slight fever developed, which was followed by systemic 
edematous erythema with itching. HPLC showed that the main components of the 
crude drug Boi are sinomenine and magnoflorine. The results of patch tests were 
negative for all oral drugs that the patient had been taking. Oral ingestion tests showed 
that the patient showed positive reactions to the as-is Boi boiling-water decoction and 
1/10-volume sinomenine. Based on this, the drug eruption was judged to be caused by 
sinomenine. It is considered the first time that the causative component of a drug 
eruption was confirmed by oral ingestion tests with components of a crude drug of 
Kampo medicine (Sino-Japanese traditional medicine).

122. Owen P. Clinical practice and medical research: bridging the divide between the 
two cultures. Br J Gen Pract 1995; 45:557-560.
Notes : The failure of the results of many research studies to be integrated into 
everyday clinical practice is both well documented and much decried. In the writings on 
why medical research and clinical practice have remained separate cultures, two 
issues have not been sufficiently debated. First, are medical researchers addressing 
the problems that cause clinicians the most concern in their consultations with 
patients, and secondly, are the results of research studies being presented in a manner 
that clinicians can both understand and use? This discussion paper highlights primary 
care clinicians' urgent need for information on the predictive value of the symptoms and 
signs seen in everyday clinical practice. Medical research has still to provide this 
information, often leaving general practitioners with inadequate predictive information on 
which to make early diagnoses, for example, on whether a patient with chest pain has 
a pulmonary embolus, or a child with pyrexia and rash has meningococcal 
septicaemia. The format in which research information is commonly presented is 
discussed; it has been shown that epidemiological terms used in studies are 
impenetrable to most clinicians. Additional ways of framing research information need 
to be devised that present such research information in a narrative format and numerical 
format, emphasizing the effects of management decisions as well as diagnostic 
categories, and for use in individual consultations as well as describing populations. 
Only then will clinicians be able to integrate into their everyday clinical practice the 
potentially valuable information provided by medical research.

123. Paparone PW, Glenn WB. Lyme disease with concurrent ehrlichiosis. J Am 
Osteopath Assoc 1994; 94:568-70, 573, 577.
Notes : Lyme disease constitutes a major health hazard with an increased incidence 
throughout the United States, in particular the eastern states. Human ehrlichiosis, also 
a tick-borne illness, has recently been identified. It is characterized by fever, headache, 
malaise, leukopenia, thrombocytopenia, and elevated liver enzyme titers, and has been 
reported to occur mainly in the South Central and South Atlantic states. As with Lyme 
disease, most patients have a history of tick exposure. These two diseases may be 
difficult to differentiate clinically. Physicians must consider the possibility of both 
infections when patients become ill with a systemic illness after tick exposure. 
Although certain demographic and clinical features are characteristic of these 
diseases, they can be misleading. Only serologic evidence can confirm the diagnosis. 
Two cases of concurrent Borrelia and Ehrlichia infections have been previously 
reported. The authors herein describe a third case that further illustrates the potential 
diagnostic dilemma posed by the concurrence of these two entities.

124. Paparone PW, Ljubich P, Rosman GA, Nazha NT. Ehrlichiosis with pancytopenia 
and ARDS. N J Med 1995; 92:381-385.
Notes : As illustrated by the case described in this report, the possibility of ehrlichiosis 
should be considered in the differential diagnosis of sulfasalazine toxicity/drug fever and 
other febrile illnesses presenting with pancytopenia/leukopenia and pulmonary 
abnormalities, when patients have been exposed to known tick-infested areas. 
Furthermore, the possibility of delayed serologic confirmation of Ehrlichia infection 
should be integrated into the diagnostic process as well.

125. Parslew R, Verbov JL. Kaposi's varicelliform eruption due to herpes simplex in 
Darier's disease. Clin Exp Dermatol 1994; 19:428-429.
Notes : A young woman with Darier's disease treated with acitretin developed Kaposi's 
varicelliform eruption, from which herpes simplex virus was isolated. Herpes simplex 
infection complicating Darier's disease is well recognized but uncommon. A young 
woman of 19 years is described who presented with fever and general malaise.

126. Pether JV, Lloyd G. The clinical spectrum of human hantavirus infection in 
Somerset, UK. Epidemiol Infect 1993; 111:171-175.
Notes : The signs and symptoms exhibited by 29 patients with an acute illness in 
whom antibodies to hantavirus were detected are described. In the severe cases the 
most striking signs and symptoms were the persistence for 2 or 3 weeks of a severe 
sore throat with pyrexia that developed early in the illness, followed by swelling of the 
face, neck and extremities, with arthropathy and prolonged malaise that lasted for 
months. A macular erythematous rash, hepatomegaly with abnormal liver function 
tests, and a tendency to haemorrhage was a later feature of the severe cases. Mild 
cases presented with a variety of signs and symptoms that were very difficult to link 
together as a syndrome.

127. Phillips WG, Weller R, Handfield-Jones SE, Kobza-Black A. Adult Still's disease. 
Br J Dermatol 1994; 130:511-513.
Notes : Adult Still's disease (ASD) is a rare disorder of unknown aetiology, 
characterized by an evanescent, erythematous, maculopapular rash, fever, arthralgia, 
and a variety of systemic features. We report a case which illustrates the typical 
features of ASD, and manifests the hitherto unreported complication of diffuse 
cutaneous mucinosis.

128. Pleasants RA, Walker TR, Samuelson WM. Allergic reactions to parenteral beta-
lactam antibiotics in patients with cystic fibrosis. Chest 1994; 106:1124-1128.
Notes : Certain antibiotics, particularly piperacillin, have been reported to be associated 
with a high incidence of allergic reactions in patients with cystic fibrosis. We initiated a 
study to determine the relative frequency of allergic reactions, ie, drug-induced fever 
and rash, to parenteral beta-lactam antibiotics in adult patients with cystic fibrosis. 
Charts of 111 patients were reviewed for each hospitalization to assess allergic 
reactions. Of 90 evaluable patients, 26 patients developed one or more allergic 
reactions to beta-lactam antibiotics. The number of allergic reactions per number of 
patients receiving specific antibiotics were carbenicillin (4/56), mezlocillin (7/42), 
piperacillin (11/31), ticarcillin (1/20), cefazolin (0/24), ceftazidime (1/35), 
imipenem/cilastatin (4/16), and nafcillin (3/36). The mean time to onset of drug-induced 
fever or of rash was 9.1 days. As a group penicillins had a higher frequency of allergic 
reactions than cephalosporins. The frequency of reactions was greatest with 
acylaminopenicillins (mezlocillin and piperacillin) and imipenem/cilastatin. The results 
of this study indicate that in addition to piperacillin, mezlocillin and imipenem/cilastatin 
may be associated with a high incidence of allergic reactions in patients with CF.

129. Price EJ, Venables PJ. Drug-induced lupus. Drug Saf 1995; 12:283-290.
Notes : Drug-induced lupus is a syndrome resembling mild systemic lupus 
erythematosus which can complicate treatment with certain apparently unrelated 
therapies. The most common individual agents are procainamide and hydralazine. 
Drugs less frequently associated with the disease are chlorpromazine, isoniazid, 
methyldopa, penicillamine, quinidine and sulfasalazine. Whole drug groups have also 
been implicated, such as the anticonvulsants, beta-blockers, sulfonamides and some 
of the newer 'biological' agents. The syndrome is characterised by arthralgia, myalgia, 
pleurisy, rashes and fever in association with antinuclear antibodies in the serum. More 
serious features of idiopathic lupus such as nephritis and cerebral disease are rare in 
drug-induced disease. The pathogenesis is unknown but in some cases is thought to 
be due to interactions between the drug and DNA or histones, rendering them 
immunogenic. For the biological agents, including interferons and antibodies to tumour 
necrosis factor-alpha, it has been suggested that it is due to disruption of the cytokine 
network. Although extremely rare, recognition of drug-induced lupus is important 
because it reverts within a few weeks of stopping the drug. It is possible that 
understanding its pathogenesis may shed light on its more serious relative, systemic 
lupus erythematosus.

130. Raab MG, O'Brien M, Hayes JM, Graham DR. Postoperative toxic shock 
syndrome. Am J Orthop 1995; 24:130-136.
Notes : PURPOSE: To determine risk factors for postoperative toxic shock syndrome 
(PTSS), a rare, rapidly progressive, and potentially fatal syndrome associated with 
postoperative wound infections. Components of PTSS include fever, rash, 
desquamation, hypotension, and multisystem organ dysfunction. METHODS: We 
conducted a retrospective review of all cases of PTSS occurring in 2 community 
hospitals from 1981 to 1993, following 390,000 surgical procedures. RESULTS: There 
were 12 cases of PTSS among the procedures reviewed (0.003%). Orthopedic 
procedures included excision of accessory navicular and patellar realignment. Wounds 
ranged from those with scant superficial exudates to those with gross purulence; all 
cultures yielded Staphylococcus aureus. All tested isolates were susceptible to 
methicillin or cephalothin. Mean time from surgery to onset of symptoms was 4 days. 
All patients had sudden onset of fever; mean maximal temperature was 40 degrees C. 
All patients displayed a rash, most in a truncal "sunburn" pattern. Eleven of 12 patients 
desquamated. All patients required vigorous fluid resuscitation. All patients survived. No 
correlation could be demonstrated between PTSS and patient age, sex, preoperative 
skin preparation or antibiotics, members of surgical team, or duration of procedure. 
CONCLUSIONS: Early recognition and treatment of PTSS are essential. No risk factors 
for PTSS have been identified. PTSS should be considered in the postoperative, acutely 
febrile, systemically ill patient, though surgical wounds may be deceptively benign in 
appearance.

131. Rege VL, Shukla P, Mascarenhas MF. Dapsone syndrome in Goa. Indian J Lepr 
1994; 66:59-64.
Notes : Daspone syndrome was noted within six weeks of starting treatment in 1.3% of 
about 700 leprosy patients on MDT reporting to the skin department of Goa Medical 
College. Skin rash, photosensitivity, fever, lymphadenopathy, sore throat, 
hepatosplenomegaly, abnormal liver function tests and raised reticulocyte count were 
consistent features in all the patients. Other drugs, infectious mononucleosis and viral 
exanthemata were considered in differential diagnosis. Withdrawal of dapsone and 
administration of prednisolone controlled the condition within three to four weeks in 
majority of the patients. One patient died of ischemic heart disease unrelated to 
dapsone syndrome.

132. Riordan FA, Sills JA, Thomson AP, Hart CA. Bacterial meningitis after MMR 
immunisation. Postgrad Med J 1995; 71:745-746.
Notes : Two children developed bacterial meningitis within five days of measles-mumps-
rubella (MMR) immunisation. Diagnosis was delayed because symptoms were 
attributed to the vaccine, although both had a raised C-reactive protein. Fever or rash 
within five days of MMR vaccination are unlikely to be due to the vaccine and a raised 
C-reactive protein suggests bacterial infection.

133. Rolan PE, Mercer AJ, Wootton R, Posner J. Pharmacokinetics and 
pharmacodynamics of tucaresol, an antisickling agent, in healthy volunteers. Br J Clin 
Pharmacol 1995; 39:375-380.
Notes : 1. Tucaresol is an orally administered antisickling agent which increases the 
oxygen affinity of haemoglobin. 2. The pharmacokinetics, effects on moderate graded 
exercise and psychometric performance of tucaresol were examined in a double-blind, 
placebo-controlled, parallel groups study in 12 healthy men. 3. Three doses of 
tucaresol were given at 48 h intervals intended to modify 15, 25 and 32.5% of a 
subject's haemoglobin to a high affinity form (%MOD). 4. Mean peak %MOD was 34%. 
Mean Cmax values in plasma and erythrocytes were 81.4 and 1459 micrograms ml-1, 
respectively. 5. Heart rate, compared with baseline, increased in the tucaresol group 
with the greatest changes at the highest %MOD and workload. There were no 
differences between groups in psychometric test performance. 6. Three volunteers on 
active drug developed fever, rash and tender cervical lymphadenopathy with onset 7-10 
days from the start of dosing, suggesting an immune mechanism. 7. The acute 
increase in oxygen affinity with tucaresol is physiologically well-tolerated, but the utility 
of tucaresol in the management of sickle cell disease will depend on the identification 
of a dosing regimen with a lower incidence of drug allergy.

134. Roland WE, McDonald G, Caldwell CW, Everett ED. Ehrlichiosis--a cause of 
prolonged fever. Clin Infect Dis 1995; 20:821-825.
Notes : Human ehrlichiosis is a recently described illness that is thought to be tick-
borne. Most recognized cases of human ehrlichiosis manifest as an acute nonspecific 
febrile illness. The natural history of untreated symptomatic disease is largely 
unknown. Over a 4-year period, we identified 41 cases of human ehrlichiosis by 
serological testing, polymerase chain reaction analysis, or both methods. The principal 
finding for six of the patients was protracted fever. The duration of their fevers ranged 
from 17 to 51 days. At the time of presentation, all six patients had clinical features, 
laboratory features, or both consistent with a diagnosis of ehrlichiosis. Polymerase 
chain reaction analysis helped to rapidly confirm the diagnosis for four of five patients 
tested. The diagnosis of human ehrlichiosis should be considered for patients with 
prolonged fever who live in an area of endemicity.

135. Rose PG, Wilson G. Advanced cervical carcinoma presenting with toxic shock 
syndrome. Gynecol Oncol 1994; 52:264-266.
Notes : Toxic shock syndrome is a multisystem disease which presents with a high 
fever, rash, gastrointestinal symptoms, and hypotension. A 58-year-old woman 
presented to the emergency room with these symptoms, hypotension and tachycardia. 
Because of vaginal spotting a pelvic examination was performed which demonstrated 
vulvo/vaginal erythema and a large vaginal mass consistent with an advanced cervical 
cancer with bilateral pelvic sidewall fixation. Cervical/vaginal biopsy demonstrated 
invasive squamous cell carcinoma and an initial chest X ray demonstrated multiple 
pulmonary metastases. After a total of 8 days of antibiotic therapy the patient received 
cis-platinum chemotherapy. The toxic shock syndrome was the presenting 
symptomatology in this patient with advanced cervical cancer. Toxic shock syndrome 
has been associated with the use of hyperabsorbent tampons as well as numerous 
other gynecologic procedures but has not been reported in patients with gynecologic 
cancer.

136. Rospond RM, Glowacki RC, Mailliard JA. Sargramostim for sulfasalazine-induced 
agranulocytosis [letter]. Clin Pharm 1993; 12:179

137. Rossi SJ, Schroeder TJ, Hariharan S, First MR. Prevention and management of 
the adverse effects associated with immunosuppressive therapy. Drug Saf 1993; 9:104-
131.
Notes : Advances in immunosuppressive therapy have resulted in significantly improved 
patient and graft survival after solid organ transplantation. However, increased use has 
brought attention to specific toxicities associated with the use of these agents. 
Corticosteroid therapy can result in a wide array of short and long term toxicities. 
Management of these effects has focused on alternate day and dosage reduction 
protocols. Myelosuppression, hepatotoxicity, alopecia and gastrointestinal adverse 
effects are associated with azathioprine and generally respond to a reduction in dosage 
or withdrawal. Cyclophosphamide myelosuppression is managed in a similar manner. 
Use of cyclosporin, while the mainstay of immunosuppressive therapy, is often 
complicated by several well documented adverse effects. Short and long term 
nephrotoxicity is often managed through pharmacokinetic dosing strategies as well as 
pharmacological intervention with calcium channel blockers, prostaglandin analogues, 
pentoxifylline and thromboxane antagonists. Cyclosporin-induced hypertension, 
hyperlipidaemia, hyperkalaemia and hyperuricaemia are generally responsive to 
appropriate dietary restrictions and pharmacological therapies. The adverse effects 
associated with polyclonal antilymphocyte agents (fever, chills, rash, arthralgias) occur 
in response to the administration of foreign protein substances but can be prevented by 
pretreatment with corticosteroids, diphenhydramine and paracetamol (acetaminophen). 
The administration of muromonab CD3 (OKT3) stimulates the release of cytokines 
resulting in potentially severe complications seen during the first 1 or 2 doses. 
Pretreatment with diphenhydramine, low dose corticosteroids and paracetamol as well 
as proper fluid management has reduced the incidence of this syndrome. However, 
agents such as high dose corticosteroids, indomethacin, pentoxifylline and anti-tumour 
necrosis factor monoclonal antibodies may further decrease the severity of cytokine-
induced toxicity. Antimurine antibodies may also develop during muromonab CD3 
therapy, potentially limiting the efficacy of this agent. However, continued concomitant 
immunosuppressive therapy has significantly reduced antibody formation. In summary, 
as newer agents are developed with narrow therapeutic windows, it will be critical to 
identify specific drug toxicity and to develop preventative and management therapeutic 
strategies.

138. Roth B, Grande PO, Nilsson-Ehle P, Eliasson I. Possible role of short-term 
parenteral nutrition with fat emulsions for development of haemophagocytosis with 
multiple organ failure in a patient with traumatic brain injury [see comments]. Intensive 
Care Med 1993; 19:111-114.
Notes : We describe a case of life-threatening haemophagocytosis after a short term 
nutrition with fat emulsion in a 21-year-old woman who sustained an isolated traumatic 
brain injury. Hypertriglyceridemia and "creaming plasma" were observed after a three-
day period of parenteral fat nutrition (Intralipid 20%). She also developed rash, high fever 

(40-41 degrees C), hypertension, raised intracranial pressure, hepatic and renal failure, 
haemolysis, marked thrombocyto- and leucopenia, coagulation disorder and pulmonary 
failure. These symptoms, together with a typical bone marrow smear, indicated 
haemophagocytosis with hyperactivation of the monocyte-macrophage system. We 
suggest that the hyperactivation was an effect of fat retention or agglutination of the fat 
particles; the initial triggering mechanism may emanate from the brain damage by 
hypercytokinaemia. The steroid treatment given most likely contributed to the 
successful outcome, as indicated by the stepwise improvement related in time to the 
steroid infusions.

139. Rubeiz N, Taher A, Salem Z, Gharzuddine W, Kibbi AG. Posttransfusion graft-
versus-host disease in two immunocompetent patients. J Am Acad Dermatol 1993; 
28:862-865.
Notes : Graft-versus-host disease may occur in certain immunocompromised patients 
after a blood transfusion. The disease is characterized by fever, a skin eruption, 
gastrointestinal disturbances, liver dysfunction, and bone marrow aplasia. Two cases of 
fatal graft-versus-host disease are reported. Both patients were immunocompetent and 
had received transfusions of nonirradiated blood from their children during surgery. The 
importance of preventing this complication by irradiating blood products given to 
patients by their first-degree relatives is underscored.

140. Rye PJ, Roberts G, Staugas RE, Martin AJ. Coagulopathy with piperacillin 
administration in cystic fibrosis: two case reports. J Paediatr Child Health 1994; 
30:278-279.
Notes : Two cases are reported of coagulopathy in association with the administration 
of piperacillin to patients with cystic fibrosis. In both cases the coagulopathy was 
associated with the development of a serum sickness-like illness with fever, rash and 
abnormal liver function tests occurring on day 12 and day 16 of treatment, respectively. 
On withdrawal of the piperacillin, both the serum sickness and the coagulopathy 
resolved rapidly, without sequelae.

141. Ryo R, Goto M, Takada M, Saigo K, Yamaguchi N, Hayashi M, et al. Diagnosis of 
post-transfusion graft-versus-host disease after formalin-fixation. Int J Hematol 1994; 
59:297-302.
Notes : A 72-year-old woman with multiple recurrence of gallbladder cancer was treated 
by intrahepatic-arterial infusion of doxorubicin using an extracorporeal system of direct 
hemoperfusion with venovenous bypass. During this treatment, the patient received 600 
ml of fresh whole blood and 30 units of platelet concentrate from five unrelated donors. 
Thereafter, high fever, skin rash over the whole body, and watery diarrhea developed, 
followed by leukopenia progressing to a fatal sepsis. Post-transfusion graft-versus-host 
disease (PT-GVHD) was suspected by the clinical manifestations and postmortem 
pathologic findings. To establish the diagnosis of PT-GVHD, polymerase chain reaction 
(PCR) amplification of DNA polymorphism associated with length variation in 
dinucleotide or trinucleotide microsatellite repeats at the loci of D6S89, int-2 
protooncogene, and human growth factor with each of the different primer sets was 
performed using DNA from blood drawn from the patient with clinically established PT-
GVHD of a donor origin and formalin-fixed pancreas of recipient origin. Genetic analysis 
revealed the changes in the patient's lymphocytes from that of the patient to that of 
donor origin. The present finding that formalin-fixed tissues can be used as a material of 
patient origin may contribute to accurate diagnosis of PT-GVHD after autopsy.

142. Sabbatini PJ. Fever and rash in a young man [corrected] [published erratum 
appears in J Tenn Med Assoc 1993 Apr;86(4):176]. J Tenn Med Assoc 1993; 86:62

143. Sahn EE, Gerscovich MJ. Ichthyosiform rash and fever in a child. Tinea corporis 
and capitis due to Trichophyton tonsurans. Arch Dermatol 1993; 129:1189, 1192

144. Saito S, Ikezawa Z, Miyamoto H, Kim S. A case of the 'dapsone syndrome'. Clin 
Exp Dermatol 1994; 19:152-156.
Notes : The 'dapsone syndrome' developed in a 44-year-old woman who was treated for 

pyoderma gangrenosum with 100 mg/day dapsone for about 5 weeks. Symptoms 
included fever, malaise, jaundice with hepatic dysfunction, lymphadenopathy, 
mononucleosis and dermatitis. These symptoms disappeared with 30 mg/day of oral 
prednisolone. A lymphocyte stimulation test with dapsone was positive, as was the 
delayed-type intradermal skin test with 0.5 and 0.05% dapsone in saline. 
Immunohistochemical studies of the rash and skin test reaction revealed that the 
dominant infiltrating T cells in the upper dermis were of the Leu 2a+ 
cytotoxic/suppressor-type rather than the Leu 3a+ helper/delayed hypersensitivity-type.

145. Sakai C, Takagi T, Oguro M, Tanabe N, Wakatsuki S. Erythroderma and marked 
atypical lymphocytosis mimicking cutaneous T-cell lymphoma probably caused by 
phenobarbital. Intern Med 1993; 32:182-184.
Notes : A 56-year-old man had been treated with phenobarbital seven weeks prior to 
admission. One month after initiation of administration of phenobarbital, fever, skin rash 
and lymphadenopathy occurred. Nine days later, marked atypical lymphocytosis, 
eosinophilia and hepatic injury was noticed. The histology of the biopsied skin was 
indistinguishable from lymphoma. CHOP-therapy was started but the patient was 
followed without further treatment because of polyclonal T-lymphocytosis. Afterward, 
clinical and hematologic improvement ensued and he has been well until now, 52 
months later. The marked T-lymphocytosis observed in this case is probably a 
lymphoid leukemoid reaction secondary to hypersensitivity to phenobarbital.

146. Salgado JH, Evans ME, Hoven AD, Noble RC. Ehrlichiosis in Kentucky. J Ky Med 
Assoc 1995; 93:132-135.
Notes : Ehrlichiosis is a recently described tick-borne disease characterized by 
headache, fever and chills, leukopenia, thrombocytopenia, and transaminase elevation. 
The presentation is similar to Rocky Mountain spotted fever but the rash is less 
frequently present in ehrlichiosis. The diagnosis is confirmed by elevated antibody titers 
to Ehrlichia chaffeensis or visualization of inclusions in white blood cells and the 
disease is easily cured with tetracyclines or chloramphenicol. Cases of ehrlichiosis are 
reported from southeastern, southcentral and midatlantic states. We report three cases 
of Ehrlichia infection acquired in Pulaski County and Fort Knox, KY during 1992-93.

147. Satake I, Tari K, Nakagomi K, Ozawa K. Feasibility and pharmacokinetics of 
continuous subcutaneous infusion of low-dose interferon-gamma: a pilot study. Jpn J 
Clin Oncol 1993; 23:356-362.
Notes : Continuous subcutaneous infusion of interferon-gamma was carried out in an 
attempt to improve the therapeutic efficacy of the agent, one of the most potent 
immunomodulatory cytokines. Seven patients with renal cell carcinoma underwent the 
therapy using battery-powered micro-infusion pumps. In four patients, recombinant 
human interferon-gamma, 15 x 10(6) JRU (Japan Reference Unit)/body, was 
administered subcutaneously and continuously for five days. The therapy was repeated 
without interruption up to three times in four patients, including one for whom a single 
course of five-day therapy had been given three months previously. The major side 
effects were fever, anorexia, general malaise and local skin reaction. Discontinuation of 
the therapy was necessary in two patients, one in single five-day therapy and the other 
in repeated therapy, due to generalized skin eruption and general malaise, respectively. 
Serum interferon-gamma levels, as determined by radioimmunoassay, increased 
gradually and reached 20-30 IU/ml on day 4 or 5. Among patients who received two or 
three courses of therapy, the interferon-gamma levels showed high inter-individual 
differences after day 6. The levels gradually fell after the therapy terminated with a half-
life of about 2 days. No clinical response was observed. Our data suggest that 
interferon-gamma can be administered by continuous subcutaneous infusion, and 
warrants further study.

148. Sato M, Takeda A, Honzu H, Saku N, Minato N, Kano S. Adult Still's disease with 
Sjogren's syndrome successfully treated with intravenous pulse methylprednisolone 
and oral cyclophosphamide. Intern Med 1993; 32:730-732.
Notes : A patient with adult Still's disease and Sjogren's syndrome failed to respond to 
conventional doses of corticosteroids. Therefore intravenous pulse methylprednisolone 
combined with oral cyclophosphamide was given which subsequently resolved the flare 
of rashes, fevers, and arthritis. This combination therapy may be a useful therapy to 
consider in patients with adult Still's disease who are resistant to conventional 
treatment and may allow a reduction in daily corticosteroid requirement.

149. Saville MW, Lietzau J, Pluda JM, Feuerstein I, Odom J, Wilson WH, et al. 
Treatment of HIV-associated Kaposi's sarcoma with paclitaxel. Lancet 1995; 346:26-
28.
Notes : We investigated whether paclitaxel was active in AIDS-associated Kaposi's 
sarcoma. We gave 135 mg/m2 intravenously over 3 hours every 21 days. Follow-up is 
available on the first 20 patients, most of whom had advanced Kaposi's sarcoma and 
severe immunocompromise. Neutropenia was the most frequent dose-limiting toxic 
effect; novel toxic effects included late fevers, rash, and eosinophilia. Creatinine 
increased in 2 patients and 1 patient had cardiomyopathy. There were 13 partial 
responses (65%, 95% CI 41-85%). All 5 patients with pulmonary involvement 
responded. Paclitaxel appears to be active against Kaposi's sarcoma as a single 
agent. Further studies, including a randomised trial, are warranted.

150. Schattner A, Sthoeger Z, Geltner D. Effect of acute cytomegalovirus infection on 
drug-induced SLE. Postgrad Med J 1994; 70:738-740.
Notes : A 58 year old woman developed systemic symptoms, interstitial lung disease, 
splenomegaly, leukopenia and anti-histone and anti-nuclear antibodies (ANA), while 
treated with hydralazine for hypertension. Five months after presentation she was 
admitted with high fever, skin rash and atypical lymphocytosis due to acute 
cytomegalovirus (CMV) infection. Worsening leukopenia and increased ANA were 
found, and high titres of anti-DNA antibodies, anti-cardiolipin antibodies and rheumatoid 
factors appeared. Hydralazine was stopped and the patient gradually became 
asymptomatic. All autoantibodies spontaneously disappeared (over 16 weeks), and the 
white cell count and spleen size became normal. The patient was found to be a slow 
acetylator and to have both HLA-DR4 and selective IgA deficiency. Thus, a 
multifactorial genetic susceptibility to develop drug-induced lupus was brought out in 
stages first by hydralazine and then by CMV, yet all manifestations and autoantibodies 
resolved spontaneously, demonstrating the complex interplay of varied environmental 
factors with a genetic predisposition in the pathogenesis of autoimmunity.

151. Schlievert PM, Gocke JE, Deringer JR. Group B streptococcal toxic shock-like 
syndrome: report of a case and purification of an associated pyrogenic toxin. Clin Infect 
Dis 1993; 17:26-31.
Notes : A patient with streptococcal toxic shock-like syndrome (TSLS) caused by 
Streptococcus agalactiae (group B Streptococcus) is described. The patient had all of 
the defining criteria for toxic shock syndrome (TSS), including fever, hypotension, 
erythematous rash, desquamation, and involvement of multiple organs. Neither 
Staphylococcus aureus nor group A streptococci were recovered, but vaginal and urine 
cultures yielded group B streptococci. The group B streptococcal isolate gave negative 
results in antibody tests for the production of TSS toxin 1, staphylococcal enterotoxins, 
and streptococcal scarlet fever toxins. However, the strain produced a novel pyrogenic 
toxin. This toxin, purified from culture fluids by ethanol precipitation, isoelectric 
focusing, and reverse-phase high-pressure liquid chromatography, had a molecular 
weight of 12,000 and an isoelectric point of approximately 7.0. The purified toxin was 
pyrogenic in rabbits, enhanced the susceptibility of the animals to lethal endotoxin 
shock, and caused the proliferation of rabbit splenocytes; these properties define 
pyrogenic toxins. When given to three rabbits via a subcutaneous miniosmotic pump, 
the toxin caused TSS-like symptoms ending in death. Three additional group B 
streptococcal strains from patients with TSLS were tested and were found to produce a 
toxin with similar properties.

152. Schumacher HR, Jr. Arthritis of recent onset. A guide to evaluation and initial 
therapy for primary care physicians. Postgrad Med 1995; 97:52-4, 57-9, 63.
Notes : Correct early diagnosis of acute and recent-onset arthritis is important to 
prognosis. The erosive damage done by rheumatoid arthritis occurs earlier in the 
disease course than previously realized, and more specific therapies to minimize 
damage are becoming available. Also, arthritis may be the initial clue to a serious 
systemic disease. Determining whether one, several, or many joints are affected can 
narrow the diagnostic possibilities. Arthrocentesis and synovial fluid testing provide 
much information and should be done at initial evaluation if possible. The presence or 
absence of fever, rash, family history of joint disease, and exposure to infective 
organisms can further direct diagnostic studies and treatment. In general, to avoid 
masking clues, drug therapy should be delayed for mild symptoms until diagnosis is 
complete.

153. Secchiero P, Carrigan DR, Asano Y, Benedetti L, Crowley RW, Komaroff AL, et 
al. Detection of human herpesvirus 6 in plasma of children with primary infection and 
immunosuppressed patients by polymerase chain reaction. J Infect Dis 1995; 171:273-
280.
Notes : A sensitive and specific polymerase chain reaction method for the detection of 
human herpesvirus 6 (HHV-6) DNA in serum or plasma has been developed. In total, 
157 human serum or plasma samples were studied. HHV-6 DNA was detected in 6 
(85.7%) of 7 children with exanthem subitum, 3 (23.1%) of 13 bone marrow transplant 
(BMT) recipients, 4 (22.2%) of 18 human immunodeficiency virus (HIV)-infected 
patients, 1 (2.6%) of 39 patients with chronic fatigue syndrome, and none of 37 healthy 
adults. In the HHV-6-positive BMT recipients, HHV-6 plasma DNA was transiently 
detected during episodes of fever and respiratory infection. In children with exanthem 
subitum and in 1 HIV-infected patient, the HHV-6 strains were characterized as variant 
B, whereas variant A was detected in all other patients. Detection of viral DNA in serum 
or plasma is a marker of active infection that can be used to investigate the role of 
HHV-6 in human disease.

154. Sehgal S, Bhardwaj M, Bhattacharya D. Immunogenicity and feasibility of purified 
chick embryo cell vaccine. Indian Pediatr 1994; 31:133-137.
Notes : Two hundred seventy-one children reported at the WHO Collaborative Centre for 
Rabies Epidemiology for South-East Asia at National Institute of Communicable 
Diseases, Delhi, for advice and antirabies antibody assessment after post-exposure 
prophylaxis with purified chick embryo cell (PCEC) antirabies vaccine from January 
1986 to October 1992. Vaccine was very well tolerated by these children and only 7% 
complained about mild to moderate side reactions like pain, induration, fever or rash. 
On an average, every year 50-55 children had reported at this Centre after post-
exposure vaccination with PCEC vaccine excepting years 1986 and 1987. One hundred 
and forty-four children underwent complete course of post-exposure prophylaxis, i.e., 5 
or 6 doses on day 0, 3, 7, 14, 30 and 90 (optional) of PCEC vaccine were administered, 
forty-three (43) children received 4 doses on day 0, 7, 14 and 30 (day 3 dose was 
omitted) and eighty-four (84) children received 2 to 3 doses as the biting animals were 
alive for 10 days in these cases. Two hundred and twenty-nine children (84.5%) were 
bitten by dogs and in 10%, the dog was proven rabid by laboratory examination of dog 
brain. One hundred and forty-nine (55%) had Class III bite. Serological response, i.e., 
antirabies antibody titre in all these children were satisfactory (> 0.5 IU/ml) with mean 
titre of 1.98 IU/ml irrespective of doses of PCEC vaccine administered. No vaccine 
failure was observed in this study.

155. Shaffer L, Giralt S, Champlin R, Chan KW. Treatment of leukemia relapse after 
bone marrow transplantation with interferon-alpha and interleukin 2. Bone Marrow 
Transplant 1995; 15:317-319.
Notes : A 16-year-old girl with refractory AML received unmanipulated BMT from an 
unrelated donor. Leukemia relapse occurred 82 days later. The patient was then treated 
with IL-2 1.8 x 10(6) U/m2 for 5 days per week and 2.5 MU/m2 IFN-alpha three times 
per week. Toxicities included fever, skin rash, somnolence and a generalized seizure. 
Treatment was stopped after 2 weeks. Acute GVHD developed at the end of therapy 
and the patient's leukemia went into remission. She died of fungal pneumonia 30 days 
later. We conclude that a combination of cytokines may be useful in treating relapsed 
leukemia after BMT.

156. Silberg SL, Bisonni R, Parker DE, Lawrence CH, Hunt L. Human ehrlichiosis--an 
overview. J Okla State Med Assoc 1993; 86:124-127.
Notes : Canine ehrlichiosis, previously thought to be restricted to dogs, has gained 
prominence in the human population since 1986. In the United States, human 
ehrlichiosis is a newly recognized disease ranging from a mild infection to a severe life 
threatening or fatal disease. Since antibody titers were found to be highest to E. canis 
in human ehrlichiosis patients, it was believed that E. canis or a closely related 
species was the etiologic agent. Investigators from the Centers for Disease Control 
recently have isolated a bacterium believed to be the etiologic agent of human 
ehrlichiosis and proposed the name Ehrlichia chaffeensis. Human cases of the disease 
have been identified primarily in the southeastern and south-central areas of the United 
States. Although relatively few cases are diagnosed, Oklahoma, according to one 
source, has been found to have the highest incidence rate. The human disease could 
be misdiagnosed as Rocky Mountain spotted fever, murine typhus fever, or Q fever.

157. Snabes MC, Martens MG. A severe puerperal group A streptococcal infection 
causing a toxic shock-like syndrome. Int J Gynaecol Obstet 1993; 40:245-248.
Notes : Toxic shock syndrome (TSS) is classically associated with vaginal recovery of 
Staphylococcus aureus during menses. In this case a patient presented with fever, 
rash, abdominal pain and signs of shock, 6 days postpartum. Blood cultures were 
negative but endometrial cultures were positive for Group A beta-hemolytic 
streptococcus. This case presents a toxic shock-like syndrome due to streptococcus, 
(toxic streptococcus syndrome) and points out the importance of culturing these 
patients for organisms other than Staphylococcus aureus.

158. Spencer JM, Silvers DN, Grossman ME. Pustular eruption after drug exposure: is 
it pustular psoriasis or a pustular drug eruption? Br J Dermatol 1994; 130:514-519.
Notes : Generalized pustular eruptions with fever present a diagnostic challenge. A 
history of preceding drug exposure, and rapid disappearance of the eruption after the 
drug is stopped, suggest a drug-induced aetiology rather than pustular psoriasis. We 
describe and evaluate the clinical and histological features of four patients who 
developed a generalized pustular eruption following drug administration. The history of 
preceding drug exposure and the presence of a variable number of eosinophils in the 
inflammatory infiltrate in the lesions of these cases suggested that the generalized 
pustular eruptions were drug-induced.

159. Stephen G, George O, Mathai D, Kaur A, Abraham OC. Dapsone syndrome. J 
Assoc Physicians India 1994; 42:72-73.

160. Strausbaugh LJ. Toxic shock syndrome. Are you recognizing its changing 
presentations? Postgrad Med 1993; 94:107-8, 111-3, 117-8.
Notes : Nonmenstrual cases of toxic shock syndrome now occur at least as often as 
the classic menstrual cases. The syndrome has been reported in every conceivable 
clinical setting involving colonization or infection with Staphylococcus aureus and as a 
complication of surgical procedures, traumatic injuries, and local infections. Unusual 
clinical manifestations have been observed in patients with AIDS. Cases of toxic shock 
syndrome also have been linked to infection with toxin-producing strains of coagulase-
negative staphylococci and group A streptococci. Knowledge of the expanding 
spectrum of toxic shock syndrome and early consideration of the disease in patients 
with fever, hypotension, rash, and/or multisystem disease are essential for timely 
diagnosis and optimum management.

161. Suzuki M, Kikkawa Y, Hasegawa T, Kaneko F. Exanthema and enanthema in 
graft versus host disease (GVHD). Fukushima J Med Sci 1993; 39:101-107.
Notes : Two cases of graft versus host disease (GVHD) were reported. Case 1: A 74-
year-old man noticed erythematous rash with high fever in fourteen days after blood 
transfusion. Skin rash spread gradually and resulted in toxic epidermal necrolysis 
(TEN) in accompany with diarrhea, liver dysfunction and pancytopenia. Case 2: A 24-
year-old man with acute lymphocytic leukemia treated with allogeneic bone marrow 
transplantation, developed macular erythema diffusely and he had received transfusion 
of peripheral buffy coat cells from his brother. Histological findings revealed eosinophilic 
necrotic keratinocytes and infiltrating cells which consisted of CD4 and CD8(+) T cells. 
The both cases were diagnosed as GVHD caused by blood transfusion, though in case 
1, differentiation from toxic eruption was needed. We described clinical and 
histopathological findings of the cutaneous manifestations of GVHD and distinction 
from some cutaneous lesions caused by drug toxicity and collagen disease.

162. Takami A, Nakao S, Miyamori H, Ooi M, Machi T, Chujo T, et al. Adult-onset 
Still's disease with submassive hepatic necrosis. Intern Med 1995; 34:89-91.
Notes : We present a 74-year old woman who was hospitalized because of typical 
spiking fever, evanescent rash, polyarthralgia, lymphadenopathy, and marked elevation 
of serum transaminases and lactate dehydrogenase (LDH) due to adult-onset Still's 
disease (AOSD) with submassive hepatic necrosis. All of the symptoms and abnormal 
laboratory findings were dramatically improved after treatment with prednisolone. The 
clinical course of this patient indicates that AOSD with severe hepatic necrosis can 
successfully be treated with early administration of corticosteroid, although it remains 
unknown whether the disease can remain in remission with no or minimal treatment.

163. Tan KK, Lee WS, Liaw LC, Oh A. A prospective study on the use of leucocyte-
filters in reducing blood transfusion reactions in multi-transfused thalassemic children 
[see comments]. Singapore Med J 1993; 34:109-111.
Notes : Two hundred and eleven blood transfusions were administered to 26 multi-
transfused thalassemic children (aged 9 months-13 years) over a 6-month period. 
Eighteen children were receiving buffy coat-poor packed red cells (PRC) prepared by 
centrifuge while 8 children received filtered blood through a leucocyte-filter (Sepacell R-
500A). Transfusion reactions occurred in 8.5% (n = 18) of transfusions and in 42.3% (n 
= 11) of patients. 11.9% (n = 16) and 2.6% (n = 2) of reactions occurred in 50% (n = 9) 
and 25% (n = 2) of patients receiving buffy coat-poor PRC and filtered blood 
respectively. Transfusion reactions in toto were significantly reduced in the group 

receiving filtered blood (p < 0.05). However, febrile reaction alone was not significantly 
reduced (p > 0.1). The median onset and duration of reaction were 2 hours (range 10 
minutes-18 hours) and 4 hours (range 1/2-24 hours) respectively. 72.2% (n = 13) of the 
reactions occurred occurred during transfusion. 88.8% (n = 16) of the reactions caused 
only one symptom. 19.2% (n = 5) of all patients had recurrent reactions, all of them 
receiving buffy coat-poor PRC. The commonest clinical manifestation was fever (n = 7), 
followed by urticaria (n = 5) and petechial rash (n = 2). The outcome was good, with no 
patient experiencing symptoms exceeding 24 hours. Only 0.9% (n = 2) of the 
transfusions were discontinued.

164. Tan YC. Rash and fever in a 3-year-old girl [clinical conference]. Ann Allergy 
Asthma Immunol 1996; 76:16-18.

165. Thies K, Anders C, Baldus M, Schleiffer T, Weber B, Rabenau H, et al. Detection 
of primary HIV infection by a second-generation HIV(p24) antigen test. Infusionsther 
Transfusionsmed 1994; 21:333-336.
Notes : We studied the course of a primary HIV infection in a 54-year-old woman. 
Probably the source of infection was sexual intercourse, since other risks, such as i.v. 
drug use, acupuncture and transfusion were excluded. On admission she presented 
with fever, a maculopapular rash, and moderate enlargement of nuchal lymph nodes. At 
that time the anti-HIV 1,2 enzyme immunoassay was negative. However, the HIV-p24 
Ag test, which was performed in every HIV screening in our laboratory, was positive. 
The suspicion of an acute HIV infection was supported by a positive HIV-cDNA-PCR 
and confirmed by Western blot after seroconversion. As additional finding, the blood 
smear showed abnormal white cell differential count, indicating viral infection. 
Aminotransferases were slightly increased, and antibodies to hepatitis B surface and 
core antigens demonstrated former hepatitis B infection. It is concluded that in this 
case the HIV-p24 Ag test proved its suitability for early diagnosis of an acute HIV 
infection. In case of testing blood donors, none of the compulsory serological screening 
methods would have detected the HIV infection.

166. Tsuda S, Kato K, Karashima T, Inou Y, Sasai Y. Toxic pustuloderma induced by 
ofloxacin. Acta Derm Venereol 1993; 73:382-384.
Notes : A patient with drug-induced toxic pustuloderma is presented. The patient, who 
was asthmatic and who was being treated with ofloxacin for bronchitis and pharyngitis, 
developed intense erythemas followed by subcorneal pustulation associated with fever 
and a neutrophil leukocytosis. The diagnosis was confirmed by oral readministration of 
ofloxacin, with the result that pustular eruptions were induced. This form of drug 
eruption had not previously been attributed to ofloxacin.

167. Uhaa IJ, Fishbein DB, Olson JG, Rives CC, Waag DM, Williams JC. Evaluation of 
specificity of indirect enzyme-linked immunosorbent assay for diagnosis of human Q 
fever [published erratum appears in J Clin Microbiol 1994 Sep;32(9):2343]. J Clin 
Microbiol 1994; 32:1560-1565.
Notes : Ninety-five acute- and convalescent-phase serum specimens from 48 patients 
suspected of having rickettsial or Legionella infections were assayed for antibodies to 
Coxiella burnetii, the causative agent of Q fever. To evaluate the specificity of the 
indirect enzyme-linked immunosorbent assay (ELISA) for human Q fever, we compared 
the ELISA results with those of the indirect immunofluorescence antibody (IFA) test. 
The ELISA data were analyzed by two different criteria for a positive test. The first 
criterion for positive results by ELISA was based upon diagnostic titers established in a 
study of 150 subjects who had no demonstrable cellular or humoral immune responses 
to C. burnetii phase I or phase II whole cells or phase I lipopolysaccharide. The second 
criterion was based upon diagnostic antibody titers in a study of 51 subjects who had 
been diagnosed as having clinical Q fever and had fourfold or greater rises in humoral 
immune responses to C. burnetii phase I and phase II whole-cell antigens. A 
comparison of the ELISA and IFA test results of the 95 serum specimens indicated 
excellent agreement between the tests (Kappa = 92.9 ; P < 0.05). None of the 38 
patients whose etiologies were confirmed serologically as Legionnaires' disease or 
rickettsial diseases other than Q fever were classified as positive for C. burnetii by the 
ELISA. Only one patient identified by the IFA test as having Q fever was not scored 
positive by the ELISA. These results suggest that the ELISA is useful for epidemiologic 
screening and as a diagnostic test for human Q fever.

168. Vena GA, Foti C, Grandolfo M, Angelini G. Mercury exanthem. Contact Dermatitis 
1994; 31:214-216.
Notes : We have observed 9 male patients with a generalized rash following the topical 
use of an over-the-counter antiparasitic powder (MOM), containing ammoniated (11.2 
g%) and metallic (4.2 g%) mercury, to treat phthiriasis (lice infestation). Primary and 
intensely erythemato-exudative lesions of the pubic region and genitals were 
associated with inverted erythema of the upper inner thighs and, in severe cases, 
involvement of the face, neck, trunk and major flexures. Eruptions included 
exanthematic, papulo-vesicular, purpuric and erythema-multiforme-like clinical pictures. 
7 of the 9 cases presented with general malaise and pyrexia. A positive patch test 
reaction to ammoniated mercury was observed in all cases. There are probably 3 
routes of powder exposure behind this type of rash: (i) direct skin contact; (ii) airborne 
skin contact; (iii) inhalation.

169. Vene S, Franzen C, Niklasson B. Development of specific antibody patterns and 
clinical symptoms following Ockelbo virus infection. Arch Virol 1994; 134:61-71.
Notes : Sixteen patients with symptoms typical for Ockelbo disease (rash, arthralgia, 
fever) were enrolled in a 2 1/2 year study, during which clinical symptoms were 
recorded and ELISA was employed to study specific IgM, IgG and IgG subclass 
development. Initially, all patients presented with rash and arthralgia, and five patients 
still suffered from joint symptoms at the end of the study period. Ockelbo virus specific 
IgM was detected during the first week post onset in 6 patients and in 15 patients by 
day 14. One patient failed to develop specific IgM and was later diagnosed with a 
human parvovirus B19 infection. All patients were IgM-negative 2 1/2 years post onset. 
Seroconversions or significant titer rises for specific total IgG were seen in 15 patients. 
IgG titers generally peaked within one year but in two patients maximum titers were 
seen 2 1/2 years post onset. Development of IgG1 followed that of total IgG, while IgG3, 
after an initial increase in all Ockelbo disease patients, remained at peak levels for one 
year in four patients, three of whom still had detectable IgG3 at the end of the study 
period. Ockelbo virus specific IgG2 or IgG4 was not detected in any of the patients.

170. Vittorio CC, Muglia JJ. Anticonvulsant hypersensitivity syndrome. Arch Intern Med 
1995; 155:2285-2290.
Notes : Anticonvulsant hypersensitivity syndrome is a potentially fatal drug reaction 
with cutaneous and systemic reactions (incidence, one in 1000 to one in 10,000 
exposures) to the arene oxide-producing anticonvulsants--phenytoin, carbamazepine, 
and phenobarbital sodium. In most cases, the hallmark features of fever, rash, and 
lymphadenopathy are accompanied by multiorgan-system abnormalities. Fatal 
outcomes are most often associated with liver failure. Recognition of the syndrome, 
which may have variable presentations, is the key to prompt discontinuation of the 
drug, close monitoring, and management. The reaction may be genetically determined, 
and siblings of patients with anticonvulsive hypersensitivity syndrome may be at 
increased risk of developing this syndrome. The timely recognition of anticonvulsant 
hypersensitivity syndrome is important, because accurate diagnosis avoids potentially 
fatal reexposure and affects subsequent anticonvulsant treatment options.

171. Vogelzang NJ, Lipton A, Figlin RA. Subcutaneous interleukin-2 plus interferon alfa-
2a in metastatic renal cancer: an outpatient multicenter trial. J Clin Oncol 1993; 
11:1809-1816.
Notes : PURPOSE: A prospective multicenter phase II trial was undertaken to define 
the activity of a low-dose subcutaneous regimen of interleukin-2 (IL-2) and interferon 
alfa-2a (IFN) in patients with metastatic renal cancer. PATIENTS AND METHODS: 
Between December 1990 and October 1991, 42 patients with metastatic renal cancer 
who had received no prior immunotherapy were treated with IL-2 (4 x 10(6) U) days 1 
through 4 and IFN (9 x 10(6) U) day 1 and 4 each week of a 4-week treatment course 
followed by a 2-week rest period. Maximum duration of therapy was 1 year. 
Concomitant therapy with acetaminophen, diphenhydramine, and indomethacin was 
recommended. Treatment was administered on an outpatient basis. RESULTS: With a 
median follow-up duration of 18 months, responses occurred in five of 42 patients (12%; 
95% confidence interval [Cl], 2% to 22%). One pathologic complete remission, one 
surgical complete remission, and three partial remissions occurred. Toxicity was 
modest, with a symptom complex of rash, fever, anorexia, fatigue, mild weight loss, 
lymphocytosis, and eosinophilia occurring in 85% to 90% of patients. Renal 
dysfunction (creatinine > 2 mg/dL) occurred in 19% of patients, while three patients 
(7%) refused further IL-2 and IFN. No toxic deaths occurred. The median survival 
duration was 14.5 months. CONCLUSION: This outpatient low-dose subcutaneous 
regimen induced mild toxicity, a modest response rate, and an excellent median 
survival duration in previously untreated patients. Phase III trials are now needed to 
compare IL-2 plus IFN with IL-2 alone or to various IL-2/IFN regimens. However, the 
major task is to identify unique new agents with activity in renal cancer.

172. Wakelin SH, James MP. Diltiazem-induced acute generalised exanthematous 
pustulosis. Clin Exp Dermatol 1995; 20:341-344.
Notes : Pustulation is a major feature in several different dermatoses, and it may also 
occur as a manifestation of drug hypersensitivity. Acute generalized exanthematous 
pustulosis (AGEP) is an uncommon eruption characterized by acute, extensive 
formation of sterile pustules, fever and peripheral blood leucocytosis. It shares several 
clinical and histological features in common with pustular psoriasis. Most reported 
cases have been triggered by ingestion of broad spectrum antibiotics, particularly 
betalactams and macrolides. There is usually rapid resolution of the eruption on drug 
withdrawal. We report the case of a 58 year-old woman who developed AGEP shortly 
after commencing treatment with the calcium channel blocker diltiazem hydrochloride. 
The eruption followed a biphasic course, and improved following treatment with 
systemic corticosteroids and methotrexate. AGEP appears to be a rare adverse 
cutaneous reaction to diltiazem, whereas a wide range of other skin eruptions have 
been reported more commonly with this drug.

173. Walker DH. Rocky Mountain spotted fever: a seasonal alert. Clin Infect Dis 1995; 
20:1111-1117.
Notes : Rocky Mountain spotted fever occurs during seasonal tick activity. A history of 
exposure to tick-containing habitats within the 3- to 12-day incubation period is a key 
epidemiological factor. The signs of fever, headache, myalgia, nausea, vomiting, and 
anorexia at onset of infection are difficult to distinguish from those of self-limited viral 
infections. Rash usually appears later and, if present, progresses through a sequence 
of stages and distribution that are never pathognomonic. The effects of disseminated 
Rickettsia rickettsii infection of endothelial cells include increased vascular 
permeability, edema, hypovolemia, hypotension, prerenal azotemia, and, in life-
threatening cases, pulmonary edema, shock, acute tubular necrosis, and 
meningoencephalitis. In severe cases, fluid management is a challenge. The clinical 
diagnosis, which is difficult, is rarely assisted by laboratory findings because antibodies 
are usually detected only in convalescence, and immunohistologic methods for 
detection of rickettsiae are unavailable in most clinics. Doxycycline is the treatment of 
choice except for pregnant or allergic patients, who are treated with chloramphenicol.

174. Ward KN, Gray JJ. Primary human herpesvirus-6 infection is frequently overlooked 
as a cause of febrile fits in young children. J Med Virol 1994; 42:119-123.
Notes : Sera from 248 children aged 30-179 weeks were tested retrospectively for 
human herpesvirus-6 (HHV-6) IgG antibody avidity. Twenty-five children presented with 
febrile fits, in one case with a rash, exanthem subitum resulting from primary HHV-6 
infection was diagnosed at the time, but in the others HHV-6 was not considered in the 
differential diagnosis even though two patients had a rash. In fact, five of the 25 patients 
experienced primary infection as shown by low avidity HHV-6 antibody. Although nine 
other of these patients were seronegative in the acute phase of the illness, and 
unfortunately convalescent sera were not available to confirm primary HHV-6 infection, 
seronegativity was clearly a risk factor for febrile fits (P = 0.03, odds ratio 3.14 for all 
children; P = 0.002, odds ratio 7.20 for children aged 70-179 weeks), and primary HHV-
6 infection was a very likely diagnosis. The remaining 11 children had high avidity 
antibody, so HHV-6 was excluded as a cause of their febrile fits. HHV-6 may frequently 
be a cause of febrile fits, often without the typical rash of exanthem subitum, and this 
diagnosis is often overlooked by clinicians.

175. Wassef M, Keiser P. Hypersensitivity of zidovudine: report of a case of 
anaphylaxis and review of the literature. Clin Infect Dis 1995; 20:1387-1389.
Notes : Hypersensitivity to zidovudine is an uncommon complication of antiretroviral 
therapy. Manifestations range from isolated fever to anaphylaxis. Fever and rash are the 
most common features. Diagnosis is made by rechallenge, although some patients 
have antibodies to zidovudine. Treatment is supportive, and symptoms resolve on 
withdrawal of the medication.

176. Weinberg WG. Safety and efficacy of teicoplanin for bone and joint infections: 
results of a community-based trial. South Med J 1993; 86:891-897.
Notes : To evaluate the efficacy and safety of teicoplanin in the treatment of gram-
positive bone and joint infections, parenteral teicoplanin was used once daily in an 
average dose of 10.1 mg/kg (range 6 to 12 mg/kg) after loading to treat patients with 
acute or chronic osteomyelitis and septic arthritis. From the 66 patients who met 
criteria for initial enrollment, 60 gram-positive isolates were recovered from bone and 
joint fluid, and each was sensitive to teicoplanin at < or = 2 micrograms/mL (median 
0.25 microgram/mL). Teicoplanin was more active in vitro against these isolates than 
either vancomycin or oxacillin. Among the 43 patients in whom microbiologic efficacy 
could be assessed, the initial pathogen was eradicated in 37 (86%). Clinically, 45 
patients infected with staphylococci (including oxacillin-susceptible and oxacillin-
resistant Staphylococcus aureus and coagulase-negative staphylococci) met 
predetermined criteria for completed adequate therapy. Of these, 39 (87%) responded 
favorably and became free of all signs of infection; 6 (13%) failed to respond or suffered 
relapse. Overall, 36 patients completed teicoplanin therapy at home. Adverse reactions 
necessitated discontinuance of therapy in 12 patients and included fever, rash, hepatic 
function test abnormalities, and renal insufficiency. We found teicoplanin to be effective 
and generally well tolerated for treatment of bone and joint infections by gram-positive 
organisms in a community setting.

177. Wielenga JJ, Vellenga E, Groenewegen A, Sonneveld P, Lowenberg B. 
Recombinant human interleukin-3 (rH IL-3) in combination with remission induction 
chemotherapy in patients with relapsed acute myelogenous leukemia (AML): a phase 
I/II study. Leukemia 1996; 10:43-47.
Notes : Patients with AML who relapse after an initial remission, have a poor prognosis. 
Administration of hemopoietic growth factors (HGFs) such as interleukin-3 (IL-3) during 
chemotherapy may result in an increased cell kill by cytotoxic agents. In addition, 
administration of IL-3 following chemotherapy may potentially accelerate hemopoietic 
recovery from chemotherapy-induced bone marrow hypoplasia. We performed an open 
labelled, phase I/II study in which patients received IL-3 by continuous infusion from 24 
h before the beginning of chemotherapy until day 28. Chemotherapy included 
daunorubicin or mitoxantrone days 1-3 and cytarabine 200 mg/m2 days 1-7. IL-3 was 
given at a dose of 5 microgram(s)/kg/day in 10 patients, 7.5 microgram(s)/kg /day in 
six patients and 10 microgram(s)/kg/day in four patients. Complete remissions (CR) 
after one cycle of this treatment were obtained in 5/10 patients and 5 microgram(s)/ kg 
group, 2/6 in the 7.5 microgram(s)/kg group and 3/4 in the 10 microgram(s)/kg group). 
Thus, 50% (10/20) of all individuals and 45% (5/11) of the elderly patients attained CR. 
Eight of 20 patients entered PR, and 2/20 patients died during the hypoplastic phase 
from infectious complications. Neutrophils and platelets recovered to 0.5 x 10(9)/l at 
day 25 (median) and to 50 x 10(9)/l at day 32, respectively. Adverse events during IL-3 
and concomitant chemotherapy were fluid retention (4/20), rash (14/20), bone pain 
(2/20), headache (10/20), chest pain (1/20), arthritis (1/20), fever and nausea. IL-3 (at 
the dose of 10 microgram(s)/kg) was discontinued in two patients because of side-
effects (fluid retention, fever, rash and chest pain), and in two other patients the high IL-
3 dose was tolerated with no problems for 29 days. Thus, IL-3 applied to patients with 
high-risk AML at dosages of 5-10 microgram(s)/kg is tolerated with acceptable toxicity 
and results in a satisfactory frequency of complete responses following a single 
treatment cycle.

178. Wolf R, Tamir A, Werbin N, Brenner S. Methyldopa hypersensitivity syndrome. 
Ann Allergy 1993; 71:166-168.
Notes : A 74-year-old man developed an extensive erythematous skin eruption, fever, 
lymphadenopathy and eosinophilia probably due to methyldopa. The symptoms 
reappeared shortly after unintentional reexposure to the drug. The positive results of two 
in vitro tests for the detection of drug allergy not only give further support to the causal 
relationship between the drug and the symptoms, but also indicate the involvement of 
an immunologic, allergic mechanism. Although every individual symptom represented in 
our case has been reported in previous cases, the association of the symptoms 
together in one patient has never before been reported. An awareness that adverse 
reactions to methyldopa can mimic a variety of acute infectious diseases and 
lymphoproliferative disorders is the key to diagnosis and might prevent unnecessary 
hospitalizations, procedures, and use of potentially toxic antibiotics and chemotherapy.

179. Wolf Y, Groutz A, Walman I, Luxman D, David MP. Impetigo herpetiformis during 
pregnancy: case report and review of the literature. Acta Obstet Gynecol Scand 1995; 
74:229-232.
Notes : A case of impetigo herpetiformis in pregnancy is reported together with a review 
of the literature. The patient was a 25-year-old primigravida with pregnancy-induced 
hypertension (PIH). At 35 weeks' gestation, the patient developed a severely pruritic 
pustular rash with fever and leukocytosis. The skin of the affected areas was biopsied 
and showed intraepidermal pustules with a neutrophilic infiltrate. Treatment 
commenced with intravenous fluids, oral prednisone, and steroid creams. Labor was 
induced, and a normal delivery of a healthy infant was effected, following which the 
patient's condition improved rapidly. The clinical and laboratory features were typical of 
impetigo herpetiformis as described in the literature. Impetigo herpetiformis is a rare, 
potentially serious skin disorder occurring particularly during pregnancy, and must be 
diagnosed early to allow prompt, aggressive treatment.

180. Wolkenstein P, Revuz J. Drug-induced severe skin reactions. Incidence, 
management and prevention. Drug Saf 1995; 13:56-68.
Notes : Severe skin adverse drug reactions can result in death, but the rate of such 
events is fortunately low. The incidences of Stevens-Johnson syndrome and toxic 
epidermal necrolysis range from 1.2 to 6 per million per year and 0.4 to 1.2 per million 
per year, respectively. Stevens-Johnson syndrome is fatal in about 5% and toxic 
epidermal necrolysis in 30% of cases. Drugs implicated in these diseases are the 
sulphonamides, anticonvulsants, allopurinol, pyrazolone derivatives, oxicams and 
chlormezanone. The principles of symptomatic treatment are the same as for burns, 
and patients with extensive skin detachment should be transferred to an intensive care 
unit or a burn centre. Hypersensitivity syndrome is characterised by mucocutaneous 
eruption and fever with frequent lymphadenopathy, hepatitis and eosinophilia. Drugs 
implicated are mainly anticonvulsants and sulphonamides. The mortality rate of such a 
reaction has been estimated to be about 8%. Corticosteroid therapy has been widely 
used in hypersensitivity syndrome, despite the lack of controlled studies. Drug-induced 
vasculitis and serum sickness may also be life-threatening when the kidney, liver, 
gastrointestinal tract or nervous system are involved. In angioedema, congestion may 
involve mucous membranes and therefore impair swallowing and ventilation. Drugs 
associated with angioedema include penicillins, radiographic contrast agents and ACE 
inhibitors. Severe forms of angioedema necessitate epinephrine (adrenaline) 
subcutaneous injection and possibly resuscitative efforts. Corticosteroids and/or 
antihistamines are used to block or reduce prolonged or late phase reactions. Prompt 
recognition and withdrawal of the suspected drug is essential in severe drug-induced 
skin reactions.

181. Wong KF, Chan JK, Ng CS. CD56 (NCAM)-positive malignant lymphoma. Leuk 
Lymphoma 1994; 14:29-36.
Notes : CD56, a natural killer cell marker reactive with the neuronal-cell adhesion 
molecule (NCAM), identifies a group of lymphomas with distinctive clinicopathologic 
features. The disease affects mostly middle-aged adults who often present with fever, 
skin rash and hepatosplenomegaly in the absence of peripheral lymphadenopathy. 
Extranodal involvement is common, particularly the skin, aerodigestive tract and central 
nervous system. Histologically, an angiocentric and angiodestructive pattern of infiltrate 
is often seen, but the cytological spectrum of the lymphoma cells is very broad. 
Cytoplasmic granules, however, are frequently found when Giemsa-stained cytologic 
preparations are examined. Immunologically, CD56-positive lymphomas can be sub-
classified into CD3-positive (T-cell) and CD3-negative (probably true natural killer cell) 
subtypes. T-cell receptor gene rearrangement can be demonstrated in the former 
cases, but not in the latter. Clinically, CD56-positive lymphomas are aggressive 
neoplasms.

182. Wood TF, Potter MA, Jonasson O. Streptococcal toxic shock-like syndrome. The 
importance of surgical intervention. Ann Surg 1993; 217:109-114.
Notes : Pyrogenic exotoxins A, B, and C produced by group A beta-hemolytic 
streptococci (Streptococcus pyogenes) may cause a syndrome characterized by fever, 
rash, desquamation, hypotension, and multi-organ-system dysfunction. This syndrome, 
the streptococcal toxic shock-like syndrome (TSLS), has a rapid and fulminant course 
closely resembling the staphylococcal toxic shock syndrome (TSS) caused by the 
staphylococcal toxic shock syndrome toxin-1 (TSST-1). The recent recognition of this 
syndrome is thought to stem from the appearance of more virulent strains of 
streptococci that have a greater tendency to produce potent exotoxins than prior 
strains. During the past 6 years, the authors have treated six patients with TSLS; three 
of these patients have presented recently. The sites of streptococcal infection 
associated with the development of the syndrome are frequently in soft tissue and skin. 
Early diagnosis, treatment with penicillin, and radical operative debridement are 
required.

183. Woolf PK. A 12 year old with fever and rash. Pediatr Emerg Care 1994; 10:249-
250.

184. Worrall GJ, Hull C, Briffett E. Radioallergosorbent testing for penicillin allergy in 
family practice [see comments]. Can Med Assoc J 1994; 150:37-41.
Notes : OBJECTIVES: To determine (a) the prevalence of patients supposedly allergic 
to penicillin who have a positive radioallergosorbent test (RAST) result for penicillin G or 
V and (b) the predictive power of family physicians' clinical judgement that a patient 
who is supposedly allergic to penicillin will have a positive RAST result. DESIGN: 
Prospective multicentre cross-sectional observational study. SETTING: Eleven primary 
care practices in Newfoundland; 10 were in a rural setting. PATIENTS: Of 110 
consecutive adult patients with a supposed allergy to penicillin 97 agreed to participate 
in the study; 92 underwent RAST. INTERVENTIONS: Patients helped physicians 
complete a questionnaire and had a venous blood sample taken for the RAST. 
Physicians examined the clinical history and judged whether the patient was likely to 
have a positive RAST result. MEAN OUTCOME MEASURES: Rates of positive and 
negative RAST results for penicillin V and G. RESULTS: Of the 92 patients 8 had a 
positive RAST result and 84 a negative one. The positive predictive power of a "good" 
clinical history (e.g., urticaria, swollen eyes, tongue or lips, or an anaphylactic reaction 
witnessed by a physician) was low (10%); the negative predictive power of a "poor" 
clinical history (e.g., nausea, vomiting, diarrhea, fever, nonspecific rash or fainting) was 
92%. CONCLUSIONS: Less than 10% of primary care patients with a supposed allergy 
to penicillin will have a positive RAST result. In addition, physicians' predictions of 
allergy in such patients are imprecise.

185. Yagupsky P, Wolach B. Fatal Israeli spotted fever in children. Clin Infect Dis 1993; 
17:850-853.
Notes : We describe three Israeli children with fatal spotted fever. Clinical disease was 
characterized by irreversible shock, encephalopathy, renal failure, bleeding tendency, 
and death within 24 hours of admission. None of the patients had a history of tick bite, 
and no tache noire was noted. One child presented without rash, and the other two did 
not have antibodies to spotted-fever-group rickettsiae. The disease was confirmed by 
isolation of Rickettsia conorii from the patients' blood and tissues in cell cultures or 
from susceptible laboratory animals inoculated with human specimens. The present 
cases demonstrate the existence of a severe form of Israeli spotted fever in this 
population that resembles Rocky Mountain spotted fever. Because Israeli spotted fever 
may follow a quick, unpredictable, rapidly fatal clinical course, specific antimicrobial 
therapy should be promptly administered whenever the diagnosis is suspected.

186. Yang CH, Yiang TG, Peng MY, Hsu GJ. Neurological complications of varicella: a 
report of two cases. Chung Hua I Hsueh Tsa Chih (Taipei) 1994; 53:253-256.
Notes : Varicella (chickenpox) is the primary infection of Varicella-Zoster virus, 
characterized by generalized vesicular eruption, fever and mild constitutional 
symptoms. Chiefly infecting children of 1 to 14 years of age, the disease has been 
almost neglected because of its inevitable and benign outcome. Adults are rarely 
infected with an incidence of less than 20%. These two cases are presented of normal 
adults with marked neurological complications 10 and 14 days, respectively, following 
typical skin eruption of varicella. The first case developed transverse myelitis and the 
second, an encephalomyelitis. Neurological complications are very rare post-varicella 
infection. Although prognosis is good and complete recovery is the rule, still some 
morbidity with neurological sequelae and mortality have been reported. The present 
cases had extensive neurological deficit, despite aggressive treatment, making a high 
index of suspicion for differential diagnosis in patients who present with encephalitis. 
Especially following the typical exanthema of varicella, this possibility is emphasized 
and the literature is reviewed.

187. Yang CH, Young TG, Peng MY, Lee HS. Cutaneous manifestation of Kikuchi's 
disease: a case report. Chung Hua I Hsueh Tsa Chih (Taipei) 1995; 55:472-475.
Notes : A 22-year-old male was admitted with a 1-month history of chills, fever, multiple 
skin eruption and painless lymphadenopathy. He has later been confirmed by typical 
histopathological findings to be a case of Kikuchi's histiocytic necrotizing 
lymphadenitis. Extranodal involvement with skin manifestation in Kikuchi's disease has 
rarely been reported; herein this unusual case is described.

188. Yoshimura T, Kurita C, Yamazaki F, Nakano S, Nagai H. Lymphocyte stimulation 
test with tetrazolium-based colorimetric assay for diagnosis of drug-induced allergic 
hepatitis. Biol Pharm Bull 1994; 17:921-926.

Notes : The lymphocyte stimulation test (LST) is useful for diagnosing drug-induced 
allergy and identifying the causative drug. In this study, we examined the usefulness of 
3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as a marker for LST 
in diagnosing drug allergy. In a basic study using normal peripheral blood mononuclear 
cells, the normal range of stimulation index (SI) was 0.92-1.38, and the mean SI for all 
drugs tested was 1.134 +/- 0.111 (mean +/- S.D.). The cut-off value of SI for diagnosis 
of drug allergy was thus set at over mean + 2S.D. for possibly positive, and at over 
mean + 3S.D. as a definitely positive reaction. Forty-six cases of suspected drug-
induced allergic hepatitis involving 85 drugs were diagnosed by this assay, and the 
possibly positive and definitely positive rates were 54.3% (SI > or = 1.4) and 41.3% (SI 
> or = 1.5), respectively. A clinical study was made of 113 patients with diagnosed 
drug-induced allergic hepatitis. Forty-nine (43%) of the patients were male and 64 
(57%) were female. In 85% of cases the allergic reaction occurred within one month of 
taking medication, but there were a number of cases in whom onset occurred after 
long-term incubation. The main clinical symptoms were jaundice, itching, eruption, 
fever, and general malaise. In about 75% of cases glutamic oxaloacetic transaminase 
(GOT) or glutamic pyruvic transaminase (GPT) returned to normal range within one 
month after medication was halted.(ABSTRACT TRUNCATED AT 250 WORDS).

189. Yu RC, Chu TC. Allopurinol-induced toxic pustuloderma [see comments]. Br J 
Dermatol 1993; 128:95-98.
Notes : We report the case of a 67-year-old man who developed a pustular eruption, 
fever, neutrophilia and eosinophilia, following a short course of allopurinol. Toxic 
pustuloderma is an uncommon form of generalized pustular eruption with several 
characteristic clinical and pathological features. A number of drugs have been 
incriminated, but to our knowledge this is the first reported case of toxic pustuloderma 
occurring after the administration of allopurinol.

190. Zimmerman RK, Pellitieri TR. Inadvertent administration of DTP and DT after age 
six as recorded in the Vaccine Adverse Event Reporting System. Fam Pract Res J 
1994; 14:353-358.
Notes : OBJECTIVE: Diphtheria and tetanus toxoids and whole-cell pertussis vaccine 
(DTP) and pediatric diphtheria and tetanus toxoids (DT) are not recommended for 
individuals > or = 7 years of age due to increased adverse reactions and the low 
pertussis case-fatality rate. Our objective was to determine if reactions to DTP and DT 
in individuals > or = 7 years of age were due to administration of pediatric DTP or DT 
instead of adult tetanus and diphtheria toxoids (Td), after adjusting for database 
inaccuracies. METHODS: We analyzed data from the Vaccine Adverse Event 
Reporting System (VAERS) reported from July 1, 1990 through March 31, 1992. 
Vaccine manufacturers were contacted to verify whether lot numbers indicated DTP or 
DT. RESULTS: According to VAERS's data, among individuals 7 years of age or older, 
26 received DTP and 77 received DT. When lot numbers were compared with 
manufacturers' records, 8 of the 77 DT doses were confirmed; 11 had incorrect or 
missing lot numbers; one was a duplicate; 56 were Td; and one was neither DT nor Td. 
Alleged adverse reactions included fever, headache, and convulsions. CONCLUSION: 
Individuals > or = 7 years of age are inadvertently receiving DTP or DT and may be 
unnecessarily experiencing adverse reactions. The 1992 VAERS database offers 
opportunities to investigate hypotheses but should be interpreted with caution due to 
inaccuracies in reporting and duplicate entries.

191. Zuckerman MA, Sheaff M, Martin JE, Gabriel CM. Fatal case of echovirus type 9 
encephalitis. J Clin Pathol 1993; 46:865-866.
Notes : Enteroviruses are rare causes of acute focal encephalitis. A fatal case of 
echovirus type 9 infection is reported in a 9 month old boy who presented with a fever 
and a macular rash followed by two focal seizures. Echovirus type 9 was isolated from 
lung tissue after seven days.