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The plants of the genus Phyllanthus (Euphorbiaceae) are widely distributed in most tropical and subtropical countries, and have long been used in folk medicine to treat kidney and urinary bladder disturbances, intestinal infections, diabetes, and hepatitis B. In recent years, the interest in the plants has increased considerably. Substantial progress on their chemistal and pharmacological properties, as well as a few clinical studies of some Phyllanthus species have been made. This review discusses the current knowledge of their chemistry, the in vitro and in vivo pharmacological, biochemical, and clinical studies carried out on the extracts, and the main active constituents isolated from different species of plants of the genus Phyllanthus. These studies carried out with the extracts and purified compounds from these plants support most of their reported uses in folk medicine as an antiviral, in the treatment of genitourinary disorders, and as antinociceptive agents. However, well-controlled, double-binding clinical trials are lacking. Several compounds including alkaloids, flavonoids, lignans, phenols, and terpenes were isolated from these plants and some of them interact with most key enzymes. Together this data strongly supports the view that the plants belonging to the genus Phyllanthus have potential beneficial therapeutic actions in the management of hepatitis B, nefrolitiase, and in painful disorders.
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PMID:A review of the plants of the genus Phyllanthus: their chemistry, pharmacology, and therapeutic potential. 966 91

Long term effects of BMT in thalassemia were monitored in 33 patients transplanted between 1987 and 1995 and compared with 155 patients matched for age and treated during the same period with conventional therapy (CT). The incidence of fulminant sepsis and growth impairment was significantly higher in transplanted patients, whereas the occurrence of hypothyroidism, hypogonadism, and cardiopathy was higher in CT patients. For diabetes, liver disease, and severe infections, the differences were not statistically significant. After BMT we performed monthly erythrocytaferesis for iron removal in 23 (70%) patients, obtaining a complete normalization of iron stores in 91% of cases; among untreated patients, 60% had evidence of iron up to 8.3 years after BMT. Protection against poliovirus, tetanus, diphtheria, and hepatitis B has been lost in 74%, 47%, 78%, and 44%, respectively. After BMT a careful follow-up is needed to monitor and treat late transplant-related and thalassemia-related complications.
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PMID:Late effects of bone marrow transplantation for thalassemia. 966 51

A case-control study was performed on 9,175 Italian adult outpatients in 5 hospitals in Rome. The study was carried out to clarify the role of some less investigated risk factors (RF) in the spread of hepatitis C virus (HCV) infection. All subjects were contacted by interviewers, who completed a questionnaire. Their sera were stored and subsequently tested for both HCV and hepatitis B virus core (HBc) antibodies. 365 subjects, positive for anti-HCV and anti-HBc-negative, and who had denied intravenous drug use (IDU) (cases) were compared with an equal number of suitable random controls negative for anti-HCV and anti-HBc. Gender, age and region of birth and residence were matched. The prevalence of 13 RFs were statistically compared by univariate and multivariate analysis. A positive anti-HCV test was significantly associated, by multivariate analysis with intravenous treatments and minor surgical procedures (both before 1975) (p < 0.001), blood transfusions (before 1991) (p < 0.01), diabetes (p < 0.01), and deliveries in hospital (p < 0.05) (both before 1975). After 1975 (1991 for transfusions), all associations lost their significance. Intra-familial (sexual and non sexual), occupational RFs and dental care were not significantly associated with the presence of anti-HCV. We suggest that non-disposable syringes, commonly used until 1975 in Italy for i.v. treatments, have been the major route for HCV transmission in Italy among non-IDU subjects.
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PMID:Sporadic hepatitis C virus infection: a case-control study of transmission routes in a selected hospital sample of the general population in Italy. 967 Mar 52

End-stage liver disease secondary to hepatitis C virus (HCV) infection is the leading indication for liver transplantation in the United States. Recurrence of HCV infection is nearly universal. We studied the patients enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Liver Transplantation Database to determine whether pretransplantation patient or donor variables could identify a subset of HCV-infected recipients with poor patient survival. Between April 15, 1990, and June 30, 1994, 166 HCV-infected and 509 HCV-negative patients underwent liver transplantation at the participating institutions. Median follow-up was 5.0 years for HCV-infected and 5.2 years for HCV-negative recipients. Pretransplantation donor and recipient characteristics, and patient and graft survival, were prospectively collected and compared. Cumulative patient survival for HCV-infected recipients was similar to that of recipients transplanted for chronic non-B-C hepatitis, or alcoholic and metabolic liver disease, better than that of patients transplanted for malignancy or hepatitis B (P = .02 and P = .003, respectively), and significantly worse than that of patients transplanted for cholestatic liver disease (P = .001). Recipients who had a pretransplantation HCV-RNA titer of > or = 1 x 10(6) vEq/mL had a cumulative 5-year survival of 57% versus 84% for those with HCV-RNA titers of < 1 x 10(6) vEq/mL (P = .0001). Patient and graft survival did not vary with recipient gender, HCV genotype, or induction immunosuppression regimen among the HCV-infected recipients. While long-term patient and graft survival following liver transplantation for end-stage liver disease secondary to HCV are generally comparable with that of most other indications, higher pretransplantation HCV-RNA titers are strongly associated with poor survival among HCV-infected recipients.
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PMID:Predictors of patient and graft survival following liver transplantation for hepatitis C. 973 79

Hepatocytes are rich in mitochondria, which play an important role in hepatic metabolism. In certain pathologic conditions (most often alcoholic liver disease) mitochondria became enlarged; nevertheless, even in these conditions they are hardly detectable on light microscopy. Recently an antimitochondrial antibody (mAM), which recognizes a 60-kDa protein, has been characterized. The purpose of the present study was to study immunoreactivity of this antibody in a series of liver biopsies. We studied 146 liver biopsies using an mAM. In 8 cases an ultrastructural study was also done, and in 2 cases Western blot analysis was performed. Cases were divided as follows: alcoholic liver disease (ALD, 31); steatosis (8); nonalcoholic steatohepatitis (NASH, 1); hepatitis C virus (HCV)-related hepatitis (83); hepatitis B virus (HBV)-related hepatitis (6); primary biliary cirrhosis (1); sclerosing cholangitis (1); haemosiderosis (1); sarcoidosis (1); alpha-1-antitrypsin deficiency (1); nonspecific findings (12). All the patients were investigated for alcohol or drug abuse, pharmacological treatment, hyperlipidaemia, hypercholesterolaemia and diabetes. Immunoreactivity was diffuse in cases of ALD, NASH and steatosis, and in patients with drug abuse. Electron microscopic immunogold and Western blot analysis confirmed that in the conditions examined the protein recognized by the mAM showed greater expression. Immunohistochemical staining was helpful in demonstrating a toxic or a metabolic insult even in cases in which the histological picture was blurred by viral infection.
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PMID:Identification of mitochondria in liver biopsies. A study by immunohistochemistry, immunogold and Western blot analysis. 976 31

Every physician taking care of pregnant women believes to be well acquainted with the state-of-the-art requirements. However, changes imposed by the new Swiss health insurance legislation (KVG) and by the pressure of Evidence Based Medicine brought these into a new scope. In Switzerland there is no general agreement on optimal pregnancy-care. We propose a care-standard, based on rational and efficient clinical, laboratory and sonographic checks, which allow a timely diagnosis of pregnancy-at-risk. Targeted laboratory investigations as well as the anti-D-immunoprophylaxis, and screening for diabetes mellitus efficiently help to avoid long-term sequelae for mother and child. Screening for toxoplasmosis, HIV, and hepatitis B are compulsory. A vaginal pH below 4.5 prevents premature birth. Diagnosis and treatment of vaginal chlamydial and candida infection are also very important in this respect. The number of sonographies to be performed during pregnancy is a highly political issue, and we have to comply with our dirigistic governmental regulations. However, sonography including search for increased nuchal translucency done early in pregnancy is a key procedure for quality assurance. Supplementation of folic acid started before conception, almost entirely prevents neural tube defects. Hence women need appropriate advice before conception. A new information brochure is available for future parents in Switzerland, and makes all former self-made guidelines unnecessary. UNICEF declared 1998 as the year of safe motherhood. Worldwide still too many women die from pregnancy and delivery. Care for normal pregnancy, and not only for at-risk-pregnancy will therefore continue to make sense.
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PMID:[Current prenatal care with reference to state of the art knowledge]. 984 65

The association between hepatitis B virus and membranous glomerulonephritis and membranoproliferative glomerulonephritis (MPGN) was first described in 1971. Recently, a similar association between hepatitis C virus (HCV) and glomerulonephritis (GN) has been reported. We investigated the prevalence of hepatitis C serum antibodies (anti-HCV) in patients with primary GN followed up at our Nephrology Outpatient Clinic between March 1993 and November 1995. The diagnosis of primary GN was established after excluding the presence of connective tissue disease, diabetes, infectious disease, and malignancy. Anti-HCV antibodies were detected by a second-generation enzyme immunosorbent assay and HCV RNA by polymerase chain reaction. Of 81 patients with primary GN, 24 had membranous glomerulonephritis, 17 MPGN, 15 minimal-change disease, 12 focal-segmental glomerulosclerosis, 9 diffuse proliferative GN, and 4 IgA nephropathy. Anti-HCV were detected in 2 cases (2.5%), both were HCV RNA positive and had a polyclonal mixed cryoglobulinemia (IgM-IgG). These 2 cases both came from the group of 17 patients with MPGN. Biochemical investigation in these patients revealed persistent elevation of serum aminotransferase activity, and a liver biopsy specimen in 1 of them showed evidence of chronic active hepatitis. We conclude that in our setting the prevalence of anti-HCV among patients with primary GN is low, being higher (11.8%) only if we consider the patients with MPGN as the reference group. Further studies are necessary to clarify this association and to determine appropriate therapy for these patients.
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PMID:Prevalence of hepatitis C virus antibodies in primary glomerulonephritis in Brazil. 984 23

The occurrence of hepatocellular carcinoma (HCC) in renal transplant recipients has typically been associated with hepatitis B or C infection. We encountered two cases of HCC in renal transplant recipients with negative hepatitis B and C markers and no underlying liver pathology, in whom immunosuppression therapy consisted of prednisone and azathioprine (AZA). Patient no. 1 is a 66-year-old man with diabetes who underwent cadaveric renal transplantation 13 years before presentation. An ultrasound obtained for evaluation of a prolonged prothrombin time and decreased serum albumin level showed a suspicious nodular lesion in the left lobe of the liver. A computed tomographic (CT) scan confirmed a 4- x 5- x 5-cm mass that, on biopsy, was determined to be well-differentiated HCC. There was no evidence of metastasis, and the results of random biopsies of the surrounding parenchyma were normal. The patient underwent a left lateral segmentectomy, did well, and an initial alpha-fetoprotein (AFP) level of 85995 ng/mL decreased to 9 ng/mL. Approximately 20 months postoperatively, however, a surveillance CT scan showed three hypervascular lesions in the right lobe of the liver and the AFP level increased to 28,370 ng/mL. Subsequent percutaneous alcohol injections yielded good results, and the patient is alive and well 13 months later. Patient no. 2 is a 57-year-old man who underwent cadaveric renal transplantation 24 years earlier. A CT scan of the abdomen obtained for evaluation of lower abdominal pain showed a 4- x 4- x 6.5-cm mass in the right lobe of the liver that, on biopsy, was found to be poorly differentiated HCC. Multiple biopsies of adjacent liver parenchyma showed no evidence of cirrhosis, AFP level was normal, and imaging studies showed no evidence of tumor spread. The patient underwent a right hepatic lobectomy and is doing well without evidence of recurrence 27 months postoperatively. Our two patients had no evidence of viral hepatitis, cirrhosis, or metabolic liver disease, yet both developed HCC. The use of AZA may have had a role in the development of HCC. In renal transplant recipients on long-term immunosuppression therapy, particularly AZA, it is prudent to maintain a high index of suspicion for HCC when liver enzyme level or function abnormalities are encountered.
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PMID:Hepatocellular carcinoma after renal transplantation in the absence of cirrhosis or viral hepatitis: a case series. 987 92

The determination of aminotranferases levels is very useful in the diagnosis of hepatopathies. In recent years, an elevated serum ALT level in blood donors has been associated with an increased risk of post-transfusion hepatitis (PTH). The purpose of the study was to research the factors associated with elevated ALT levels in a cohort of voluntary blood donors and to evaluate the relationship between increased ALT levels and the development of hepatitis C (HCV) infection. 166 volunteer blood donors with elevated ALT at the time of their first donation were studied. All of the donors were questioned about previous hepatopathies, exposure to hepatitis, exposure to chemicals, use of medication or drugs, sexual behaviour, contact with blood or secretions and their intake of alcohol. Every three months, the serum levels of AST, ALT, alkaline phosphatase, gamma glutamyl transpeptidase, cholesterol, triglyceride and glycemia are assessed over a two year follow-up. The serum thyroid hormone levels as well as the presence of auto-antibodies were also measured. Abdominal ultrasound was performed in all patients with persistently elevated ALT or AST levels. A needle biopsy of liver was performed in 9 donors without definite diagnostic after medical investigation. The presence of anti-HCV antibodies in 116 donors were assayed again the first clinical evaluation. At the end of follow-up period (2 years later) 71 donors were tested again for the presence of anti-HCV antibodies. None of donors resulted positive for hepatitis B or hepatitis C markers during the follow-up. Of the 116 donors, 101 (87%) had persistently elevated ALT serum levels during the follow-up. Obesity and alcoholism were the principal conditions related to elevated ALT serum levels in 91/101 (90.1%) donors. Hypertriglyceridemia, hypercholesterolemia, hypothyroidism and diabetes mellitus also were associated with increased ALT levels. Only 1/101 (0.9%) had mild chronic active non A-G viral hepatitis and 3/101 (2.9%) had liver biopsy with non-specific reactive hepatitis. The determination of ALT levels was not useful to detect donors infected with HCV at donation in Brazil, including the initial seronegative anti-HCV phase.
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PMID:Elevated alanine aminotransferase (ALT) in blood donors: an assessment of the main associated conditions and its relationship to the development of hepatitis C. 987 34

While patients with liver disease are known to have a higher prevalence of glucose intolerance, preliminary studies suggest that hepatitis C virus (HCV) infection may be an additional risk factor for the development of diabetes mellitus. To further study the correlation of HCV infection and diabetes, we performed a retrospective analysis of 1,117 patients with chronic viral hepatitis and analyzed whether age, sex, race, hepatitis B virus (HBV) infection, HCV infection, and cirrhosis were independently associated with diabetes. In addition, a case-control study was conducted to determine the seroprevalence of HCV infection in a cohort of 594 diabetics and 377 clinic patients assessed for thyroid disease. In the former study after the exclusion of patients with conditions predisposing to hyperglycemia, diabetes was observed in 21% of HCV-infected patients compared with 12% of HBV-infected subjects (P =.0004). Multivariate analysis revealed that HCV infection (P =.02) and age (P =.01) were independent predictors of diabetes. In the diabetes cohort, 4.2% of patients were found to be infected with HCV compared with 1.6% of control patients (P =.02). HCV genotype 2a was observed in 29% of HCV-RNA-positive diabetic patients versus 3% of local HCV-infected controls (P <.005). In conclusion, the data suggest a relatively strong association between HCV infection and diabetes, because diabetics have an increased frequency of HCV infection, particularly with genotype 2a. Furthermore, it is possible that HCV infection may serve as an additional risk factor for the development of diabetes, beyond that attributable to chronic liver disease alone.
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PMID:Association of diabetes mellitus and chronic hepatitis C virus infection. 1044 86


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