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.

Clear cell sarcoma kidney: clinical features and outcome.

Clear cell sarcoma of kidney (CCSK) is a rare, highly malignant tumor. The clinical features and treatment outcome of 12 patients with CCSK are reported. From 1982 through December 1996, 12 cases of CCSK were seen at the Regional Cancer Centre, Trivandrum, India. Patients were staged according to NWTS III recommendation. They were treated with chemotherapy containing vincristine, actinomycin, and Adriamycin and radiotherapy. The survival curve was calculated by the Kaplan-Meier method. Mass and pain in the abdomen were the presenting symptoms. Male/female ratio was 3:1. Six had stage I, 4 had stage II, and 2 had stage III disease. Of the 12, 10 were evaluable, 6 are alive, and 3 recurred in 9 evaluable. Six patients are alive free of disease 10 to 108 months after diagnosis. The overall survival and disease-free survival of the 10 patients are 64 and 56%. It would appear that combined modality treatment can cure two thirds of children with CCSK. Effective treatment needs to be developed for children who fail after first line treatment.

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.

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.

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.

Focal masses in cirrhotic liver: CT and MR imaging features.

The development of hepatic cirrhosis triggers attempted repair through regenerative nodules of parenchyma among bands of scar tissue. Some authors believe that this regeneration initiates an evolutionary process that may lead to nodular enlargement and cellular dedifferentiation to malignancy. Both the destructive and reparative processes in cirrhosis produce changes that the radiologist must recognize when imaging the cirrhotic liver. This essay describes the CT and MR features of masses and masslike lesions in the cirrhotic liver, including the identifying characteristics and overlapping appearances of CT and MR.

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.

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.

Liver biopsy through the femoral vein.

A technique to perform a liver biopsy through the femoral vein with the Mansfield biopsy forceps is described. Nine liver biopsy procedures were performed in seven patients who were considered at high risk of bleeding, precluding a conventional transperitoneal biopsy. The technique is an easy, safe, and well-tolerated procedure and is an alternative to the traditional transjugular approach.

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.

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.

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.

Selective immunoglobulin A deficiency associated with primary biliary cirrhosis in a family with liver disease.

A family is described in which multiple members are afflicted with liver disease and primary biliary cirrhosis (PBC). In the third generation, one member died of PBC, and a second individual has both symptomatic PBC and selective immunoglobulin A (IgA) deficiency, an association not previously reported. By culturing this patient's lymphocytes in vitro it was shown that the IgA deficiency was due to a failure of B cells to secrete IgA. Two other siblings of this patient have multiple serum biochemical and serologic abnormalities that are sometimes associated with PBC, but they do not have histopathologically overt PBC or IgA deficiency. All three surviving family members have a diminished autologous mixed lymphocyte reaction, an immunologic abnormality that has previously been found in patients with PBC, selective IgA deficiency, and several autoimmune diseases. As there is an association between selective IgA deficiency and certain autoimmune diseases, it is possible that this immunodeficiency contributed to the development of PBC in the patient in whom the two diseases coexisted. Furthermore, the occurrence of PBC in a patient with selective IgA deficiency indicates that the pathogenesis of PBC does not require IgA-dependent immune mechanisms.

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.

Halothane hepatitis without halothane: role of inapparent circuit contamination and its prevention.

Halothane and other halogenated anesthetic agents are liquids which are highly soluble in rubber and plastic materials widely used as components of anesthesia machines. These agents must be administered using machines equipped with vaporizers. We report a patient with a past history of halothane hepatitis in whom recurrence was suspected despite the fact that halothane had been avoided purposely during the subsequent operation. Circumstances led us to believe that inapparent circuit contamination of vaporizer-equipped anesthesia machine with halothane may be responsible for the inadvertant rechallenge and recurrence of halothane hepatitis. Vaporizer-equipped machines were tested for inapparent contamination with halothane and enflurane using Perkin-Elmer mass spectrometer. Oxygen alone was passed through the anesthesia circuits, and gas in the efferent limbs of the machines was tested for halothane (in eight machines) and enflurane (in two machines) which were found in various concentrations in all machines so tested. Our findings suggest that inapparent contamination may be widely prevalent in vaporizer-equipped anesthesia machines. The validity of this conclusion was confirmed in five patients with previous diagnosis of halothane hepatitis who subsequently underwent operations under general anesthesia during which machines never equipped with vaporizers were successful in preventing recurrence of hepatitis. We conclude that patients with a prior history of halothane hepatitis are at risk of inapparent circuit contamination-induced recurrent hepatitis. Unless such contamination can be confidently excluded, vaporizer-equipped machines should not be used to administer general anesthesia in these susceptible patients.