Reye's syndrome in adults. Diagnostic considerations.

Reye's syndrome (RS) is generally considered a childhood disease. We report our experience with RS in adults in the metropolitan Milwaukee area. Reye's syndrome was diagnosed in seven 18- to 46-year-old adults. The diagnostic criteria were as follows: viral prodrome followed by vomiting and encephalopathy without focal neurological signs, normal cerebrospinal fluid values, increased levels of serum aminotransferases (transaminase), prolonged prothrombin time, elevated blood ammonia levels, and characteristic microvesicular fatty liver and mitochondrial changes. None of the patients was hypoglycemic. The diagnosis of RS was entertained in 22 but confirmed in only seven patients. In cases of non-Reye's encephalopathy, drug ingestion presented as one of the most difficult differential diagnostic problems, which also included alcohol abuse, collagen vascular disease, and hepatitis B surface antigenemia. Clinical jaundice, distinctly uncommon in RS, was present in only one patient who presented to us in stage V coma. In adults, RS is more difficult to diagnose and should be suspected more frequently in patients with unexplained altered behavior following a viral illness and vomiting. Liver biopsy can be performed safely and is usually mandatory in adults. Patients with RS diagnosed during stage I or II coma and treated experienced an uneventful recovery.

Fulminant hepatitis associated with disulfiram. Report of a case.

Disulfiram is used commonly as reinforcement in the treatment of chronic alcoholism. Although the drug is generally considered safe, there are reports of side effects including psychosis and hepatitis. We report a case of fatal fulminant hepatitis caused by the use of disulfiram in a man with previously normal hepatocellular function.

Long-term effects of vasectomy on pituitary-gonadal function in man.

Plasma concentrations of testosterone (T), follicle stimulating hormone (FSH), and luteinizing hormone (LH) and percent binding of T to plasma protein (TB) were studied in 16 normal fertile men and in 81 men who had undergone vasectomy from 1 to 5 yr earlier. No significant difference from the control values to T = 582 plus or minus 39.5 (SE) ng/100 ml; FSH = 15.09 plus or minus 2.18 (SE) mIU/ml; LH =10.03 plus or minus 1.13 (SE) mIU/ml and TB = 92.99 plus or minus 0.285 (SE) % binding was detected in any group of the vasectomized men in any of the parameters studied.

Childhood oligodendrogliomas presenting with seizures and low-density lesions on computed tomography.

Three children with cerebral oligodendrogliomas causing partial complex or generalized seizures presented with completely normal neurologic examinations. CT showed low-density, nonenhancing surface lesions. Although these CT features are usually associated with infarcts or cysts, neoplasm was suspected because of irregularity of the margins and erosion of the adjacent inner table of the skull. Oligodendrogliomas often enlarge slowly and may cause seizures years before they produce focal neurologic signs. CT of all children with seizures not responsive to anticonvulsant medication and focal clinical or EEG abnormalities will hasten diagnosis of slowly growing intracranial mass lesions.

Phenobarbital treatment and major depressive disorder in children with epilepsy.

The prevalence and severity of psychopathology in 15 epileptic patients treated with phenobarbital and 24 patients treated with carbamazepine were compared. The groups were similar across a wide range of demographic, seizure-related, and family-environmental variables. Patients treated with phenobarbital, when compared with those treated with carbamazepine, showed a much higher prevalence of major depressive disorder (40% v 4%, P = .02), and suicidal ideation (47% v 4%, P = .005) as determined by semistructured psychiatric interviews. The differential prevalence of depression between medication groups was only noted in those with a family history of a major affective disorder among first-degree relatives. Family discord and number of stressful life events were also associated with depression in this cohort. Patients treated with phenobarbital should be closely monitored for depression, and alternative treatments should probably be sought for patients with newly diagnoses epilepsy and a personal or family history of an affective disorder. The clinical and research implications of these findings are discussed.

High-dose vitamin E supplementation does not diminish ribavirin-associated haemolysis in hepatitis C treatment with combination standard alpha-interferon and ribavirin.

BACKGROUND: Ribavirin is associated with haemolytic anaemia. Antioxidants have been reported to decrease severity of this anaemia. AIM: To determine effect of vitamin E supplementation on ribavirin-associated haemolysis in chronic hepatitis C treated with standard alpha-interferon and ribavirin. METHODS: Fifty-one naive chronic hepatitis C patients were randomized to receive either alpha-interferon/ribavirin therapy (control) or therapy plus vitamin E 800 IU b.d. with 24-week follow-up. Alanine aminotransferase ALT, haemoglobin and reticulocyte percentage were monitored. Symptoms and health-related quality of life were also monitored at each visit. RESULTS: Forty-seven subjects were treated (27 vitamin E /20 controls). Thirteen withdrew because of adverse effects or non-compliance. Groups were similar in demographics, genotype and baseline lab indices. Comparison with baseline, treatment and follow-up values showed a significant haemoglobin and ALT reduction in both groups. There was no significant difference in haemoglobin and reticulocyte percentage between groups. Sustained viral response was not significantly different between vitamin E (11/18) and control (6/16) groups. Three patients required ribavirin dose-reduction in the vitamin E group compared with two controls. Health-related quality of life during and end-of-treatment was not different between groups. CONCLUSIONS: Vitamin E supplementation alone during standard alpha-interferon and ribavirin therapy does not appear to diminish ribavirin-associated haemolysis.

Venereal transmission of hepatitis B virus. The possible role of vaginal secretions.

The presence of Type B viral (Australia antigen related serum) hepatitis in vaginal specimens was investigated and compared with that in saliva specimens in a group of patients during the acute phase of their illness. Hepatitis B surface antigen was detectable in most vaginal and salivary secretions during the phase of antigenemia and not in hepatitis B surface antigen-negative controls. Despite care in collection, occult blood was detected in the majority of specimens, but the positivity for hepatitis B surface antigen did not depend on the presence of occult blood. Recovery studies were performed in both vaginal fluids and saliva to determine if inhibitors to hepatitis B surface antigen were similar to those observed in stool samples. Significant inhibition was not observed. Although infectivity of the specimens was not established from this study, handling of these specimens as potentially infective material is recommended.

Pregnancy in cirrhotic and noncirrhotic portal hypertension.

The course of pregnancy in 1 patient with chronic active hepatitis (CAH) and cirrhosis, and another with extrahepatic portal vein obstruction (EHPVO) is described. The management of pregnancy in these diseases associated with portal hypertension is discussed and risks of pregnancy are compared. The patient with CAH presented with anovulatory cycles, and ovulation occurred following immunosuppressive therapy. Both women experienced massive upper gastrointestinal bleeding from esophageal varices. Bleeding was difficult to control and required variceal ligation in 1. Both patients manifested features suggesting cerebral edema indicating the need for caution with fluid and electrolyte therapy. Recovery of the woman with CAH after termination of pregnancy was slow. Review of literature demonstrated that variceal bleeding occurred in 43% of women with EHPVO compared to 23% of those with CAH and cirrhosis. Additional complications including hepatocellular failure (24%) occurred in patients with CAH but not in EHPVO. The management of pregnancy in portal hypertension and advice for contraception or sterilization are discussed.

Exchange transfusion in hepatic coma: factors affecting results, with long-term follow-up data.

1. Exchange transfusion in our experience has produced a response in 42 per cent of the patients. 2. Complicating factors, primarily sepsis, have been responsible for a 50 per cent mortality in those patients who initially respond, yielding a survival rate of 21 per cent. 3. In a select group of patients with infectious hepatitis under the age of twenty-five years, the survival rate was 37.5 per cent. 4. Excess bilirubin and ammonia rebound after exchange transfusions indicates a grave prognosis. 5. All survivors have normal results on liver function studies.

Phenotypic correction of activated protein C resistance following orthotopic liver transplantation.

A 43-year-old white female underwent orthotopic liver transplantation in 1992 for cirrhosis related to primary sclerosing cholangitis. Pre-transplantation protein S (PS) studies revealed a discrepancy between PS activity and free PS antigen consistent with type II PS deficiency. Since the presence of activated protein C (APC) resistance has been reported to interfere with PS activity assays resulting in an apparent type II PS deficiency, we retrospectively tested a pre-transplantation frozen plasma sample for APC resistance. The sample was found to have an abnormal APC resistance ratio (APCR-R) of 1.71. Follow up testing 2 1/2 years post-transplantation revealed correction of the APC resistance phenotype (normalization of the APCR-R to 2.79). Analysis of DNA extracted from lymphocytes revealed the patient to be heterozygous for the FV mutation associated with APC resistance (FV Leiden). Hereditary APC resistance was confirmed by family studies which revealed the presence of APC resistance and heterozygous FV Leiden in her son. Although the patient's post-transplantation plasma FV is normal, her platelet FV remains heterozygous for FV Leiden. To what extent, if any, platelet FV Leiden in the absence of plasma FV Leiden may contribute to a predisposition to thrombosis is unknown.

Oral verrucous carcinoma. An analysis of 37 cases.

37 cases of oral verrucous carcinoma, occurring over a period of six years from 1981-1986, were analysed in respect of the clinical, radiological and histological findings. A delineation of the clinical presentation of this tumour, and the relation of habits to the occurrence of the lesion, has been clarified. The connotation of the term verrucous hyperplasia and its differences from verrucous carcinoma, have been discussed. Surgery and radiotherapy both seem to give good results as methods of treatment, especially when coupled with adequate nutrition and cessation of harmful habits.

Intensive chemotherapy in children with stage IV neuroblastoma.

A retrospective analysis of effectiveness of sequential chemotherapy with cyclophosphamide, doxorubicin, cisplatin and etoposide in children with stage IV neuroblastoma was undertaken. Study group included 17 children of mores than one year old with median age of 3 years (range 18 months to 7 years). Fourteen were males and three females. Sites of primary tumor were abdomen in 12 patients, pelvis in 3, paravertebral in 1 and unknown in 1. Metastatic sites included bone marrow (88%), bone (82%), orbit (29.4%) and lymph node (11.7%). One patient had brain parenchymal disease and another had cerebrospinal fluid positivity for malignant cells. Fifteen of the 17 patients had major response with chemotherapy (complete response in two and partial response in 13). Ten of the 15 patients completed four courses of chemotherapy and five patients progressed while on chemotherapy and died. Only two of the ten patients, who had four courses chemotherapy are alive after 2 years. Hence the 2-year survival in this series is 11.7%. There was no toxic death in this study.

Hepatitis B surface antigen carrier state in neonates. Prophylaxis with large doses of conventional immune human serum globulin.

Acute type B viral hepatitis developed near the term of pregnancy in seven women. All had signs of acute hepatitis at delivery, and hepatitis B surface antigenemia persisted two to four weeks after delivery. Two milliliters of conventional immune human serum globulin was administered to the neonates within a week of birth, after preexisting type B viral hepatitis infection was excluded. The antibody against hepatitis B surface antigen (anti-HBs) content of two of the administered batches of immune human serum globulin was 1:32 and 1:64. None of the babies became hepatitis B surface antigen carriers, and anti-HBs developed without obvious clinical hepatitis in one baby. Conventional immune human serum globulin in larger doses may be a relatively safe and effective prophylaxis against the development of hepatitis B surface antigen carrier state even if the anti-HBs content in the administered dose is relatively small.

Central nervous system effects of civet.

Civet, the perineal gland secretion of Malabar Civet cat (Moschothera civettina blyth) in doses ranging from 100 to 800 mg/kg p.o. produced significant potentiation of pentobarbitone induced hypnosis, mild analgesis and anticonvulsant activities. However, it is devoid of hypothermic effect in mice and antipyretic activity in febrile rats. It also failed to produce any effect in the "rota - rod test", to influence the amphetamine toxicity in aggregated mice and in the conditioned avoidance response in trained rats. In the acute toxicity studies civet was found to be devoid of any toxic manifestations or mortality in mice upto a dose of 800 mg/kg orally.

Gold induced hepatitis and pure red cell aplasia. Complete recovery after corticosteroid and N-acetylcysteine therapy.

A 54-year-old man developed severe cholestatic jaundice and pure red cell aplasia shortly after beginning treatment with gold sodium thiomalate. Although the hepatic toxicity began to spontaneously improve, the pure red cell aplasia was progressive. Treatment with prednisone and N-acetylcysteine (NAC) infusions was followed by prompt and complete hematologic recovery. Gold induced pure red cell aplasia should be added to the list of gold induced hematologic toxicities that can be potentially reversed with NAC infusion therapy.

Suloctidil-induced hepatotoxicity.

Suloctidil is a new drug that is currently being evaluated in many clinical trials for use in dementia and thrombotic disorders. Hepatotoxicity has to date been reported exclusively in the European literature, and the few available histologic descriptions have been reported in the French language. We report a case of suloctidil-induced hepatotoxicity documented by serum liver biochemical tests and liver biopsy. Histologic features included focal necrosis of hepatocytes, mild hyperplasia of Kupffer cells, and other features suggestive of mild acute hepatitis.

Recurrent nonalcoholic steatohepatitis and cirrhosis after liver transplantation.

Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis and lead to liver failure. Histologically, NASH is often indistinguishable from liver disease caused by alcohol use; the cause of NASH remains unknown. A subgroup of patients with NASH eventually develops fibrosis and/or cirrhosis, and in many cases, transplantation is performed for end-stage liver disease attributed to steatohepatitis in patients who do not consume alcohol. The patient described received a transplant for end-stage liver disease secondary to NASH with cirrhosis. Postoperatively she did well, with a bout of mild rejection treated successfully at week 9 with prompt normalization of liver tests. Weight and glycemic control were optimized, and steroid therapy was minimized as safely as possible. Repeat liver biopsy at week 66, however, for persistent mild elevation of alkaline phosphatase and gamma-glutamyl-transferase surprisingly revealed the "recurrence" of NASH. Subsequent biopsy revealed NASH with cirrhosis by week 76 after transplantation. Subsequent biopsy at week 87 has confirmed cirrhosis. The patient does not consume alcohol. It is believed to be the first reporting of such a case.