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Biomedical subjects

G Borgia

Publications and source records attributed to G Borgia.

At least 19 recordsLinked to original sources

Treating chronic hepatitis B: today and tomorrow.

Three hundred and fifty million people worldwide are estimated to be chronically infected with hepatitis B virus. 15-40% of these subjects will develop cirrhosis, liver failure or hepatocellular carcinoma during their life. The treatment of chronic hepatitis B has improved dramatically over the last decade thanks to the advent of nucleoside/nucleotide analogues and the use of pegylated interferons. However, these agents have increased the complexity of the management of hepatitis B. Five drugs have been approved for chronic hepatitis B treatment: standard interferon-alpha 2b, pegylated interferon-alpha 2a, lamivudine, adefovir dipivoxil, and entecavir. A definite course of standard or pegylated interferon is administered to induce hepatitis B virus clearance. Unfortunately, these agents are not effective in all patients and are associated with not negligible side effects. Nucleoside or nucleotide analogues that inhibit hepatitis B virus polymerase induce on-treatment suppression of viral replication but patients tend to relapse after cessation of treatment. Consequently, these analogues, which are well tolerated, should be used for prolonged periods, even indefinitely. However, prolonged treatment is associated with a high rate of resistance. The following anti-hepatitis B virus drugs are currently undergoing clinical testing: telbivudine, emtricitabine, tenofovir disoproxil fumarate, clevudine and thymosin-+/-1. Here we will examine the mechanism of action, efficacy, safety, tolerability and emergence of resistance of agents used to treat chronic hepatitis B. We shall also examine the potential of drugs now being tested and of combination treatment.

Antiviral Agents↗

[Cystic echinococcosis in humans: our clinic experience].

Echinococcosis in humans is a zoonotic infection caused by larval stages of cestode species of the Echinococcus genus. In cystic echinococcosis (CE), caused by Echinococcus granulosus, the liver is the first and the more frequent involved organ, followed by the lung. Heart, spleen, kidney and brain are usually less involved. The finding of a cyst in course of echinococcosis is usually fortuitous, during ultrasound examination, X-ray or CT. The Authors report 4 cases of human CE admitted to the Department of Infectious Diseases University of Naples "Federico II". Each case is peculiar both for the organ involved by the cysts and for the symptomatolgy. The abdominal pain, in case 1 caused by gallstones, allowed, by the ultrasound examination, to find several hydatid cysts in the liver, never symptomatic until then. The woman, in case 2, was operated for cysts in the lung, without receiving pharmacological prophylaxis. The same occurred in case 4, in which the lack of prophylaxis caused very serious relapses. In case 3, the young woman underwent an ultrasound examination because of an abdominal pain. A unique large cyst extended only in the spleen. The specific serology for immunoglobulin anti-E. granulosus resulted positive 1:61 (n.v. < 50). The Albendazole therapy caused the disappareance of pain, quickly. Later, the patient was splenectomized. It's not clear why only the spleen was involved and why the anti-E. granulosus serum levels of were increased only a little. The man, in case 4, was admitted with chest pain and electrocardiographic findings of myocardial anterior ischemia. He underwent surgical treatment of three hepatic cysts by E. granulosus, during the previous year. Two-dimensional echocardiography, transesophageal echocardiography, and cardiac magnetic resonance revealed a round cystic mass, 6 x 6 mm, located in the middle interventricular septum. The cardiac isoenzymes were in the normal ranges, but the anti-E. granulosus immunoglobulins were positive 1:5120 (n.v. < 64). The patient was treated with Albendazole. This caused the almost simultaneous disappearance of the circular cystic and clinical and electrocardiographic findings of myocardial ischemia. A cardiac hydatid cyst is an uncommon lesion, occurring in about 0.4-2% of patients with echinococcosis. In conclusion, Cystic echinococcosis is a problem in Mediterranean regions because of the high population of stray dogs, favourable conditions created by man and, above all, the illegal slaughtering.

Abdominal Pain↗

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.

Aged↗

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.

AIDS-Related Opportunistic Infections↗

Loss of preferred mates forces female satin bowerbirds (Ptilonorhynchus violaceus) to increase mate searching.

Variation in mate choice among females can have important consequences for the operation of sexual selection, and can result from differences in the way females search for mates. Our previous work indicates that female satin bowerbirds Ptilonorhynchus violaceus alter their mate-searching patterns according to long-term experience. Females which mate with very attractive males mate with the same males in the following year, thereby reducing their search. In contrast, females which fail to encounter very attractive males typically reject their previous mates and search for more attractive males in the following year, thereby increasing their search. Here we report results from a natural experiment consistent with these observations. Five males, including the most attractive male of 1997, failed to re-establish display sites in 1998, most probably dying over winter. We monitored the mate-searching behaviour of females which mated with these males in 1997 to determine how the loss of attractive mates affects subsequent mate-searching patterns. Females which lost their mates sampled more males compared with their own search patterns in 1997 and with faithful females in 1998. Results from this natural experiment indicate that the loss of attractive and preferred mates forces females to increase their search and provide evidence that long-term experience with males shapes mate-searching behaviour.

Animals↗

HCV and GBV-c/HGV infection in HIV positive patients in southern Italy.

Flaviviridae-hepatitis C virus (HCV) and GB virus C/hepatitis G virus (GBV-C/HGV)--and human immunodeficiency virus (HIV) frequently show similar modes of transmission. HCV and GBV-C/HGV infection was assessed in 134 consecutive patients with evidence of HIV infection, living in Campania, Italy. Data obtained from this cohort were compared with those obtained from 252 age- and sex-matched HCV infected patients without evidence of HIV infection (HCV control group). Following enzymatic immunoassays, samples were tested for the presence of HCV-RNA by RT-PCR. The HCV-RNA positive sera were genotyped by LiPA procedure. The prevalence of HCV infection in HIV patients was 19.40% and the largest group of HIV-HCV co-infected patients (84.62%) was represented by intravenous drug users (IVDU). The distribution of HCV genotypes in HIV-HCV patients was different, compared to that observed in HCV control group. HCV genotypes la (50%) and 3a (23.08%) were more frequently detected in HIV HCV patients, compared to HCV control group (5.16 and 5.56% for la and 3a, respectively). Conversely, HCV genotypes lb (55.70%) and 2a/2c (30.26%) were more represented in HCV control group, compared to HIV-HCV patients (15.38 and 0% for lb and 2a/2c, respectively). GBV-C/HGV seroprevalence was 41.04% in HIV patients and 6.54% in healthy control individuals. Differently from HCV, GBV-C/HGV infection did not correlate to a preferential risk behaviour in the HIV cohort. Comparative analysis of HCV and GBV-C/HGV infection indicates that the use of injecting drugs might play a key role in the epidemiology of HCV and, in particular, of la and 3a HCV genotypes, in HIV patients.

Adult↗

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.

Antiviral Agents↗

Multivariate discriminant function based on six biochemical markers in blood can predict the cirrhotic evolution of chronic hepatitis.

BACKGROUND: Serologic markers have been proposed for monitoring hepatic fibrosis in chronic active liver disease. Because none of these markers, when used singly, is totally satisfactory, we developed and evaluated a multivariate approach. METHODS: We studied two cohorts of chronic hepatitis (54 patients) and cirrhosis patients (49 patients) to identify a panel of biochemical markers that discriminates between the two diseases. Using multivariate discriminant analysis, we selected a function, based on the concentrations of six biochemical markers (fibronectin, prothrombin, pseudocholinesterase, alanine aminotransferase, manganese superoxide dismutase, and N-acetyl-beta-glucosaminidase). We then prospectively validated this function on a second temporal cohort of patients. RESULTS: Multivariate discriminant analysis correctly classified 93.7% of patients (94.3% of chronic hepatitis and 92.9% of cirrhosis patients) in the first cohort and 85% of patients (89.5% of chronic hepatitis patients and 81% of cirrhosis patients) in the second cohort. CONCLUSIONS: Discriminant analysis of results of six inexpensive biochemical markers provides a high predictive value for differentiation between liver cirrhosis and chronic hepatitis. Consequently, these biochemical markers condensed into a multivariate discriminant analysis value for each patient provide information that can be contributory for subsequent options during the evolution of the natural history of chronic hepatitis.

Biomarkers↗

Co-option of male courtship signals from aggressive display in bowerbirds.

The pre-existing trait hypothesis suggests that females evolve a mating preference for an already existing male trait. This hypothesis poses a simple resolution to Darwin's long-standing question of how elaborate, male display traits evolve. The frequently observed convergence of aggressive and courtship displays across a wide array of species provides the only current support for this hypothesis. Here we provide much more detailed supporting evidence from bowerbird skrraa calls used in aggression and courtship. Consistent with the pre-existing trait hypothesis we show that (i) putatively co-opted skrraa calls used in courtship and aggression are homologous, (ii) skrraa calls were used in aggression in bowerbirds before being used in courtship, (iii) historically, intense, aggressive-like courtship calls were present near the time of co-option, and (iv) bower types contemporaneous with co-option emphasize design features that provide females protection from the adverse effects of intense courtship displays. These results, plus evidence for a female preference for males with intense aggressive-like courtship skrraa calls, suggest that aggressive skrraa calls have been co-opted for use in male courtship display

Aggression↗

Dynamic mate-searching tactic allows female satin bowerbirds Ptilonorhynchus violaceus to reduce searching.

Females can maximize the benefits of mate choice by finding high-quality mates while using search tactics that limit the costs of searching for mates. Mate-searching models indicate that specific search tactics would best optimize this trade-off under different conditions. These models do not, however, consider that females may use information from previous years to improve mate searching and reduce search costs in subsequent years. We followed female satin bowerbirds Ptilonorhynchus violaceus during mate searching and reconstructed their search patterns. We found that females who chose very attractive males typically mated with the same male in the following year, resulting in these females sampling fewer males than those who switched mates. In contrast, females who mated with less attractive males typically rejected their previous mates and searched longer for more attractive mates in the following mating season. A potential cost to mate searching is suggested by the observed increase in the likelihood of force-copulation attempts from marauding males with increased searching. Our results suggest that by using past experiences to adjust their search tactics, females may obtain high-quality mates while limiting search costs. These results emphasize the need to consider historical effects in studies of sexual selection, especially for long-lived species with stable display sites.

Animals↗

Sexual selection drives rapid divergence in bowerbird display traits.

Sexual selection driving display trait divergence has been suggested as a cause of rapid speciation, but there is limited supporting evidence for this from natural populations. Where speciation by sexual selection has occurred in newly diverged populations, we expect that there will be significant differences in female preferences and corresponding male display traits in the absence of substantial genetic and other morphological differentiation. Two allopatric populations of the Vogelkop bowerbird, Amblyornis inornatus, show large, qualitative differences in a suite of display traits including bower structure and decorations. We experimentally demonstrate distinct male decoration color preferences within each population, provide direct evidence of female preferences for divergent decoration and bower traits in the population with more elaborate display, and show that there is minimal genetic differentiation between these populations. These results support the speciation by sexual selection hypothesis and are most consistent with the hypothesis that changes in male display have been driven by divergent female choice.

Animals↗

Increased serum concentrations of soluble HLA-class I antigens in hepatitis C virus related mixed cryoglobulinaemia.

OBJECTIVE: To investigate whether quantitative alterations of both beta(2)microglobulin (beta(2)micro) associated HLA class I heavy chains (sHLA-I) and beta(2) micro free class I heavy chains (sHLA-FHC) in sera of patients with hepatitis C virus (HCV) infection occur and whether they distinguish patients with mixed cryoglobulinaemia (MC). METHODS: 83 HCV infected patients were studied and divided into three groups: (A) without cryoglobulinaemia (n=21), (B) with polyclonal MC (n=20), (C) with monoclonal MC (n=42). Serum sHLA-I and sHLA-FHC were measured by double determinant radioimmunoassay using monoclonal antibodies: TP25.99 as catching antibody, and NAMB-1 and HC-10 as revealing antibodies. Western blot identified HLA-I isoforms. RESULTS: The serum concentrations of sHLA-I and of sHLA-FHC in HCV infected patients versus controls were respectively 1.3(0.5) microg/ml (mean (SD)) versus 0.8 (0.3) (p<0. 001) and 13.9 (7.1) ng/ml versus 9.2 (5) (p<0.001). sHLA-I were 1.01 (0.4) microg/ml in group A, 1.04 (0.4) microg/ml in group B, and 1. 47 (0.4) microg/ml in group C (p=0.001). Statistical analysis showed a significant difference versus controls for groups B (p<0.02) and C (p<0.001). sHLA-FHC were 12.8 (8.3) ng/ml in group A, 17.2 (7.1) ng/ml in group B, and 12.9 (6.2) ng/ml in group C (p<0.02). A significant difference versus controls for each group was found (p<0. 02, p<0.001, and p<0.02, respectively). Different patterns of sHLA-I isoforms were observed. CONCLUSIONS: Increased serum concentrations of sHLA-I and sHLA-FHC characterise HCV infected patients. The highest sHLA-I concentrations seem to distinguish patients with monoclonal MC. In this last condition sHLA could play a part in the HCV escape and in B cell proliferation. The significance of sHLA-FHC is still undefined.

Adult↗

[Diagnosis and surgical treatment of primary hyperparathyroidism].

Primary hyperparathyroidism (HPP) is increasingly being recognized because of the widespread use of multiphasic screening for hypercalcemia, in patients without clinical signs. Each year develop 100,000 new cases in the United States, females/males 5:2; the peak of incidence is in V-VI degrees decade. We analyze our patients from November 1975 to July 2000. We have performed 112 parathyroidectomy for HPP, 84 females and 28 males, median age 57.5 years. We have examined the surgical options, the value of PTH, calcium, and the number of pathological glands. The Authors discuss the invasive or non-invasive procedures and the surgical treatment.

Adolescent↗

Coevolution of elaborated male display traits in the spotted bowerbird: an experimental test of the threat reduction hypothesis.

Elaborated male sexual displays commonly involve multiple elements that may differ greatly among closely related species, but there have been few studies of the causes of this divergence. Male spotted bowerbirds, Chlamydera maculata, have unusually intense, aggressive courtship displays and highly divergent bowers. Male and female courtship positions differ from related species in that males court females separated by a modified see-through bower wall. Here we experimentally tested hypotheses that could explain the unique features of spotted bowerbird display relative to other Chlamydera species. Our results support the threat reduction hypothesis, which suggests that accessory traits evolve because they mitigate the threat associated with intense, aggressive male displays that are most effective in causing females to become sexually receptive. In spotted bowerbird males, the highly modified and unique see-through bower walls allow females to view intense displays while reducing threat that would otherwise be associated with these same displays. We found that (1) females preferred males with the most intense displays, (2) males and females at experimentally manipulated bowers consistently moved to courtship positions so that the standing bower wall separated them and (3) males reduced display intensity when not separated from the female by an intact bower wall. Comparisons with other Chlamydera species suggest that bower architecture coevolves with other display elements to allow maximally effective male displays. Such coordinated adaptive changes of display elements suggest an alternative to the runaway divergence of arbitrary traits as the cause of rapid divergence in multifaceted male display traits among closely related species. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

Sexual transmission of hepatitis C virus and prevention with intramuscular immunoglobulin.

The sexual transmission of hepatitis C virus (HCV) has long been debated. The prevalence of infected at-risk partners varies from 0% to 30%. In a prospective study, the risk of infection was quantified in steady heterosexual partners and the prophylactic effect of normal human polyvalent immune serum globulin (ISG) was evaluated. A total of 899 at-risk partners of HCV-infected patients were enrolled in a single-blind randomized controlled trial and assigned to receive every 2 month 4 mL of intramuscular ISG from unscreened donors (450 partners) or placebo (499 partners). Seven partners developed acute HCV infection (increased aminotransferase levels and appearance of HCV-RNA): six of the placebo group (incidence density [ID] 12.00/1,000 person year; 95% confidence interval [CI] 3.0 to 21.61), and only one of the ISG-treated group (ID 1.98/1,000 person year; 95% CI 0 to 5.86). The risk of infection was significantly higher in controls versus treated individuals (p = 0.03). Six couples had genotype 1b (85%), and one couple had genotype 1a; HCV sequence homology strongly supported sexual transmission. Our trial demonstrates that HCV infection can be sexually transmitted and quantifies the risk of sexual transmission: for every year of at-risk sexual relationship, almost 1% of the partners became infected. Intramuscular ISG is safe and well tolerated. Unlike ISG from screened donors, ISG from donors unscreened for anti-HCV contains high titers of anti-gpE1/gpE2 neutralizing antibodies and high neutralizing activity. Anti-HCV hyperimmune globulin could be prepared from anti-HCV-positive blood units and could be used to protect sexual partners and in other at-risk situations of exposure to HCV infection.

Adult↗

Sexual transmission of the hepatitis C virus and efficacy of prophylaxis with intramuscular immune serum globulin. A randomized controlled trial.

OBJECTIVE: To estimate the risk of sexual transmission of hepatitis C and to assess the value of prophylaxis with periodic intramuscular immune serum globulin administration. METHODS: Of 1102 steady heterosexual partners of patients with antibodies to the hepatitis C virus (HCV), 899 were enrolled in a single-blind, randomized, controlled trial. All the partners tested negative for antibodies to HCV and had normal baseline serum aminotransferase concentrations. The partners were assigned to receive 4 mL of 16% polyvalent immune serum globulin prepared from unscreened donors every 2 months (n = 450) or a placebo (n = 449). Tests for HCV infection were performed every 4 months. RESULTS: Eight hundred eighty-four partners completed the study. Seven partners became infected with HCV: 6 in the control group (incidence density, 12.00 per 1000 person-years; 95% confidence interval, 3.0 21.61) and 1 in the immune serum globulin group (incidence density, 1.98 per 1000 person-years; 95% confidence interval, 0-5.86). The risk of infection was significantly higher for partners in the control group (P = .03): for each year approximately 1% of the partners became infected. Sequence homology studies strongly suggest the sexual transmission of HCV. All immune serum globulin lots used had high enzyme-linked immunosorbent assay titers of neutralizing antibodies to HCV envelope glycoproteins and high neutralization titers in the neutralization of binding assay. CONCLUSIONS: Hepatitis C can be sexually transmitted. Immune serum globulin prepared from unscreened donors significantly reduced the risk. The treatment was safe and well tolerated. Because only immune serum globulin from unscreened donors (and not from those screened for HCV) contain anti-HCV neutralizing antibodies, hyperimmune anti-HCV immune serum globulin should be prepared from blood testing positive for antibodies to HCV, which is currently discarded.

Adult↗

Labile evolution of display traits in bowerbirds indicates reduced effects of phylogenetic constraint.

Bowerbirds (Ptilonorhynchidae) have among the most exaggerated sets of display traits known, including bowers, decorated display courts and bright plumage, that differ greatly in form and degree of elaboration among species. Mapping bower and plumage traits on an independently derived phylogeny constructed from mitochondrial cytochrome b sequences revealed large differences in display traits between closely related species and convergences in both morphological and behavioural traits. Plumage characters showed no effect of phylogenetic inertia, although bowers exhibited some constraint at the more fundamental level of design, but above which they appeared free of constraint. Bowers and plumage characters, therefore, are poor indicators of phylogenetic relationship in this group. Testing Gilliard's (1969) transferral hypothesis indicated some support for the idea that the focus of display has shifted from bird to bower in avenue-building species, but not in maypole-builders or in bowerbirds as a whole.

Animals↗

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.

Adult↗