Myasthenia gravis during low-dose IFN-alpha therapy for chronic hepatitis C.

We describe the case of a 56-year-old man who had high aminotransferase levels and anti-hepatitis C virus (HCV) antibodies. He underwent liver biopsy and biochemical screening to evaluate whether he would benefit from interferon (IFN) treatment. The patient was discharged with a diagnosis of HCV-related active chronic hepatitis, skin porphyria, and type 2 diabetes. On December 5, 1995, he began therapy with recombinant IFN-alpha at a dose of 3 MIU three times a week. He stopped this therapy in February 1996 because of asthenia, diplopia, headache, and anxiety. During IFN therapy, he had normal aminotransferase levels and no detectable HCV RNA, a condition that persists to the present. Between March and May 1996, the patient was admitted several times to a neurology clinic, where myasthenia gravis was diagnosed and treatment with pyridostigmine and cyclosporine was initiated. This case and others indicate that caution should be exercised in administering IFN because low doses can be correlated with myasthenia gravis in patients without malignancies.

Prevalence and signification of antinuclear and anticardiolipin antibodies in patients with epilepsy.

PURPOSE: To determine the prevalence of autoantibodies in patients with epilepsy and to find a possible relationship between antinuclear antibodies (ANA) and/or anticardiolipin (aCL) antibodies and epilepsy. PATIENTS AND METHODS: One hundred sixty-three consecutive, unselected patients followed at the Centre Saint-Paul, a French medical center specialized in epilepsy, were included in the study. IgG and IgM class aCL antibodies were measured by an enzyme-linked immunosorbent assay (ELISA). IgG class ANA was detected by an indirect immunofluorescence technique with Hep2 cells as the substrate. Sera from 100 healthy blood donors, matched for age and sex, were used as controls. RESULTS: In 31 sera, IgG class a aCL antibodies were detected at a value higher than 17 GPL unit (19%, P = 0.0003); 10 of them had a value higher than 35 GPL unit. IgM class aCL antibodies were not detected at a significant value. For 6 of the 31 sera, there was a beta 2-glycoprotein I dependence. None of the patients with aCL antibodies in the serum had a past history of deep venous or arterial thrombosis. ANA were detected in the sera from 41 patients (25%, P < 0.005). The presence of autoantibodies in the serum was not statistically dependent on the type of epilepsy, the kind of antiepileptic drug, or the age or sex of the patients. CONCLUSIONS: Our study suggests that there is a relationship between epilepsy and aCL antibodies, even in the patients without systemic lupus erythematosus. Large prospective studies are needed to define the role of the aCL antibodies and ANA in pathophysiology of epilepsy.

Bronchial asthma healthcare costs in Mexico: analysis of trends from 1991-1996 with information from the Mexican Institute of Social Security.

Cost trends for bronchial asthma have not been previously estimated in Mexico. The increasing prevalence of bronchial asthma as well as its elevated costs make it necessary to expand the availability of information for health planners. This is a growing problem which has been given little attention in national health reports. We did a descriptive, retrospective analysis using national data from the Mexican Institute for Social Security. We estimated the number of medical consultations provided by the state family medicine and specialty areas. A total of 756,843 consultations due to bronchial asthma were provided between 1991 and 1996 in the service areas under study. The healthcare expenditure for bronchial asthma showed an ascending and sustained trend during the study period. When analyzing the trends by type of service, a significant increase in in-hospital care was observed, ranging from US $14.5 (1991) to $19.8 (1996) million and a maximum of $28.4 (1994) million. A similar increase was found in specialty consultation, from $3.96 (1991) to $8.5 (1996) million; in emergencies, from $1. 1 (1991) to $2.9 (1996) million; and family medicine, from $0.66 (1991) to $0.79 (1996) million. Bronchial asthma follows the same pattern as other noncommunicable chronic diseases, increasing in highly urbanized areas and nationwide. In order to improve healthcare and maximize results with scarce resources, a set of strategies is presented to reduce bronchial asthma recurrence, decrease healthcare costs, and improve quality of life.

[Intranuclear particles in chronic non-A, non-B hepatitis: what diagnostic significance?]. / Particelle intranucleari in corso di epatite cronica NANB: quale utilità diagnostica?

Intranuclear particles of 23-27 nm diameter have been repeatedly demonstrated in the nuclei of hepatocytes of patients with non-A, non-B hepatitis and of experimentally infected chimpanzees; however, their specificity has been challenged since they have also been observed in other pathological conditions and in healthy volunteers. We have conducted an ultrastructural study of liver biopsies from 10 patients with chronic active non-A, non-B hepatitis. The intranuclear particles, which were observed in all patients, were classified according to the aggregation patterns described by De Vos. Eight patients (80%) had particles of type 2. A reevaluation our proceeding data on Delta hepatitis demonstrated that no particles of type 2 were present. These results support the hypothesis that only type 2 particles are markers of non-A, non-B hepatitis.

Intrahepatic cholestatic jaundice related to administration of ranitidine. A case report with histologic and ultramicroscopic study.

Ranitidine may cause liver injuries ranging from transient, subclinical serum transaminases increase every 100-1,000 treated patients to cholestatic hepatitis in less than 1/100,000. Other H2-receptor antagonists are more dangerous: 11 toxic hepatitis cases have been reported as adverse effect after 1 year of marketed ebrotidine. A 75-year-old male with ischemic cardiopathy history was started on an 8 days treatment of oral ranitidine due to pirosis, without any other changes of therapy; 48 h after drug withdrawal, light-coloured stools, dark urine and icteric scleras developed. On hospital admission, 10 days later, physical examination showed slight hepatomegaly and severe jaundice with skin excoriations followed by serum mixed bilirubin further increase and aminotransferases activities mild rise. Total bilirubin peaked at 381.33 mmol/l (5.1-17.1) and progressively returned to normal, after discharge home, in 3 months and now, 1 year later, there is no sign of liver disease. Ultrasonographic biliary anomalies and the most frequent causes of liver damage were excluded. Liver biopsy confirmed ranitidine as the most likely cause of liver toxicity since histological and ultramicroscopical study revealed a drug-induced picture. We report a rare case of intrahepatic cholestasis jaundice related to ranitidine, a widely used drug. Diagnosis would need an ethically unacceptable rechallange test.

HIV and hepatitis C virus: facts and controversies.

Hepatitis C virus (HCV) infection occurs in about one-third of HIV-seropositive patients and in about 90% of HIV-positive drug abusers. After the introduction of highly active antiretroviral therapy (HAART) and the subsequent reduction in mortality from opportunistic infections, HCV-related liver failure has become a frequent cause of death in HIV-positive patients. In HIV-seropositive patients, the course of HCV infection is accelerated and there is evidence that HCV is an important factor for HIV progression. Consequently, it is important to establish the appropriate treatment for HCV infection in HIV-seropositive patients. This review examines the epidemiology, physiopathology, diagnostics and treatment of HIV/HCV coinfection with particular regard to the impact of HAART.

Mycelium-yeast transition in Histoplasma capsulatum. Early ultrastructural changes.

The ultrastructural changes which occur during the first 24 h of mycelium to yeast transition have been studied in the dimorphic fungus Histoplasma capsulatum. A temperature shift controls mycelial to yeast transition. During the first 24 h respiratory rate, ATP and cytochrome concentration fall to very low levels. Ultrastructural observations showed that the plasma membrane became undulated and the cell wall lost its characteristic fibrous outer layer. At 8 h the ordered lamellar structure of the mitochondria was no longer apparent. 24 h after the temperature shift 70% of the cells were lysed. The remaining cells contained many cytoplasmic membrane structures; mitochondria were rarely observed. These changes are considered to be the morphological expression of the physiological events characteristic of stage one in mycelial to yeast transition.

Aetiological association of virus like particles with hepatitis C.

Isolation of virus-like particles from sera of anti-HCV positive patients and their ultrastructural characterization are reported. Particles were identified in sera of 5 out of 6 patients tested. Immunoelectron microscopy assay revealed small aggregates of viral particles. Size and morphological criteria suggest that these particles can be classified as Togaviridae.

[Ultrastructural study of the mycelium-yeast transition in Histoplasma capsulatum. I. Changes at 37 degrees C]. / Studio ultrastrutturale sulla transizione micelio-lievito in histoplasma capsulatum: I. Cambiamenti a 37 gradi C.

Ultrastructural changes observed during the first 24 hours of mycelium to yeast transition in the dimorphic fungus Histoplasma capsulatum are reported. During this period the plasma membrane becomes undulated and the cell wall loses its characteristic fibrous outer layer. At 8 h the ordered lamellar structure of the mitochondria is no longer apparent. 24 h after the temperature shift 70% of the cells are lysed. The remaining cells contain many cytoplasmic membrane structures; mitochondria are rarely observed. These morphological changes are probably correlated with the physiological events characteristic of mycelial to yeast transition.

Prevalence of circulating immunecomplexes and variations of complement fractions in HBV, HDV and HCV infections: statistical analysis and clinical correlations.

Increased levels of circulating immunecomplexes (CIC) have been demonstrated in the serum of patients with HBV infection and HDV superinfection. This finding appears to be correlated to the disease's activity. In this report serum levels of two fractions of CIC (CIC-Clq and CIC-C3d) were evaluated by ELISA method in a sample of 110 subjects with hepatitis infection (HBV, HCV, HDV). Reference values were obtained in a group of 45 healthy subjects (blood donors). Both the CIC fractions were increased in the patients with HCV infection. The most significant increase for both CIC-C1q and CIC-C3d was found in the cirrhotic patients. The complement fractions C3c and C4 were determined in the serum of these patients to investigate a potential pathogenic role of such immunecomplexes. C3c and C4 fractions showed a significant decrease only in the cirrhotic patients, without correlation with the viral agent. Serum levels of C1q complement fraction were not significantly decreased, thus excluding an impaired synthesis of complement fractions. No significant correlation was found between CIC and C3c and C4 fractions in patients with increased levels of CIC, except a slightly significant correlation between reduction of C3c and increase of CIC-C1q. These data suggest a pathogenic action of immunecomplexes in the course of HCV, particularly in the cirrhotic stage.

[Ultrastructural study of the yeast-mycelium transition in Histoplasma capsulatum. II. Changes at 34 degrees C]. / Studio ultrastrutturale sulla transizione micelio-lievito in Histoplasma capsulatum: II. Cambiamenti a 34 gradi C.

The ultrastructural changes which occur during the mycelium to yeast transition in Histoplasma capsulatum induced by a temperature shift from 25 degrees C to 34 degrees C are described and compared to those observed after a temperature shift from 25 degrees C to 37 degrees C. 24 hours after the temperature shift to 34 degrees C only 8% of the cells are lysed. However, many mitochondria have lost their characteristic elongated form and have become rounded. Vesicular cristae which are no longer oriented parallel to the long axis of the mitochondria are also observed. In contrast a temperature shift from 25 degrees C to 37 degrees C induces lysis of 70% of the cells; mitochondria are rarely observed in the remaining cells. These ultrastructural changes can be correlated with the uncoupling of oxidative phosphorylation and the production of heat shock proteins.

The effect of temperature on the ultrastructure of Histoplasma capsulatum during the mycelium-yeast transition.

The ultrastructural morphology of the early phases of mycelium-yeast transition in Histoplasma capsulatum after a temperature shift from 25 degrees C to only 34 degrees C is described. Under this condition of lower temperature oxidative phosphorylation is not completely uncoupled and maximum production of heat shock proteins (hsp) occurs. 24 h after temperature shift more than 90% of the cells still appear vital. Alterations in the organization of the mitochondrial cristae are the only ultrastructural changes observed in these cells. In contrast, 70% of the cells degenerate 24 h after a temperature shift from 25 degrees C to 37 degrees C and in the remaining cells mitochondria are rarely observed. These observations are discussed in relation to the production of hsp, the uncoupling of oxidative phosphorylation and the virulence of different strains of H. capsulatum.

Prevalence of intranuclear particles in liver pathologies.

An ultrastructural study of the prevalence of electron dense 23-27 nm intranuclear particles was carried out on liver biopsies from patients with NANB chronic active hepatitis (CAH), Delta + CAH, HBsAg + CAH, nonviral liver pathologies and in one healthy volunteer. The particles were classified according to aggregation pattern and were found to be correlated with NANB CAH and Delta + CAH. No particles were observed in nonviral liver pathologies. A close antigenic relationship has been shown between the cytoplasmic alterations observed in NANB and delta hepatitis in chimpanzees. Our data indicate that there is a structural similarity between the intranuclear particles seen in both Delta and NANB hepatitis, thus reinforcing the hypothesis that the NANB and Delta agents are closely related.

[Measurement of sIgA in patients with chronic stable bronchitis]. / Cuantificación de la SIgA en pacientes con bronquitis crónica estable.

As we know secretory IgA of respiratory system has a very important role in defense mechanism. We studied 100 human beings, 50 healthy persons and 50 chronic bronchitis patients. Lavage nasal samples were tacked from healthy persons and sputum samples from chronic bronchitis patients. The laboratory test was nefelometry laser. Samples were analyzed was 1 student. Our results showed light increased of IgA in chronic bronchitis patients not significative. We concluded that this light increased is secondary to continuous stimulus of bronchial mucous as a part of defense mechanism.

A case of paracoccidioidomycosis: experience with long-term therapy.

We describe long-term therapy for paracoccidioidomycosis occurring in a 61-year-old house-painter from Venezuela. The diagnostic examinations made in South America had shown pulmonary granulomatous lesions and an osteolytic pattern of the left knee that had been considered suspect of malignant disease with an indication for limb amputation. With the aid of fine needle aspiration biopsy (FNAB) and culture examination we diagnosed an osteomyelitis by Paracoccidioides brasiliensis and initiated therapy with itraconazole, 400 mg per day, reduced to 200 mg per day after 2 months. At the end of 2 years of drug therapy, we observed complete regression of the pulmonary lesions and of the osteolytic area of the left knee. Moreover, we have periodically observed our patient to verify his clinical development and he is still in good health. We suggest that this pathology be considered in differential diagnosis of leprosy, tuberculosis, leishmaniasis, and systemic mycoses, even in non-endemic areas.

Ultrastructural effects of PCMS on mycelial-yeast transition in Histoplasma capsulatum.

The Yeast phase of Histoplasma capsulatum has stringent growth requirements. Transition from mycelium to yeast takes place only in the presence of cysteine and can be blocked by the -SH groups inhibitor p-chloromercury-phenylsulfonic acid (PCMS). Ultrastructural studies show lysis and degeneration of PCMS treated mycelium grown at 37 degrees C for 24 hours. Only 50% of PCMS treated mycelium appear degenerate when grown at 34 degrees C for 24 hours. The remaining cells have normal morphology with only slight changes in the cell wall structure. The effect of PCMS is permanent and hereditary. Mice injected with PCMS treated mycelium do not develop disease and are resistant to virulent strains of H. capsulatum when challenged.

Prevalence of hepatitis C virus genotypes in southern Italy.

HCV is ubiquitous. In 50% of all cases it causes chronic hepatitis that often evolves into liver cirrhosis and hepatocellular carcinoma. Recently HCV has been classified in 5 genotypes by Okamoto. The purpose of this study is to evaluate the prevalence of 5 genotypes in Campania, a region of southern Italy, where the prevalence of anti-HCV antibodies ranges from 0.87 to 4%, and to evaluate the correlation between the HCV genotypes and the severity of histological damage. One-hundred- and-thirty-five anti-HCV positive patients were enrolled and tested by PCR to identify HCV-RNA. One-hundred-and-twenty-four patients resulted HCV-RNA positive. Genotyping was performed as described by Okamoto et al. with minor modifications of the specific primer to type III proposed by Silini et al. Eight patients were negative for all genotypes. Eight patients were positive for type I(1a), 61 for type II(1b), 39 for type III(2a), 11 for type IV(2b) and 1 for type V(3a). In 4 cases two different genotypes were present in the same sample [II(1b)-IV(2b), III(2a)-II(1b) twice, III (2a)-IV(2b)]. Histological evaluation of liver damage showed: CPH (22 cases), minimal CAH (56), severe CAH (31) and liver cirrhosis (15). There was no statistically significant correlation between the 5 genotypes and the severity of histological damage. Data on the prevalence of genotype II (1b) in Italy are similar to those reported for other European countries. The prevalence of genotypes in southern Italy is similar to that reported in the population of northern Italy.