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Biomedical subjects

S C Gordon

Publications and source records attributed to S C Gordon.

At least 19 recordsLinked to original sources
PubMed2001

Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.

BACKGROUND: A sustained virological response (SVR) rate of 41% has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this randomised trial, peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin. METHODS: 1530 patients with chronic hepatitis C were assigned interferon alfa-2b (3 MU subcutaneously three times per week) plus ribavirin 1000-1200 mg/day orally, peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin, or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000-1200 mg/day for 48 weeks. The primary endpoint was the SVR rate (undetectable hepatitis C virus [HCV] RNA in serum at 24-week follow-up). Analyses were based on patients who received at least one dose of study medication. FINDINGS: The SVR rate was significantly higher (p=0.01 for both comparisons) in the higher-dose peginterferon group (274/511 [54%]) than in the lower-dose peginterferon (244/514 [47%]) or interferon (235/505 [47%]) groups. Among patients with HCV genotype 1 infection, the corresponding SVR rates were 42% (145/348), 34% (118/349), and 33% (114/343). The rate for patients with genotype 2 and 3 infections was about 80% for all treatment groups. Secondary analyses identified bodyweight as an important predictor of SVR, prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight (mg/kg). Side-effect profiles were similar between the treatment groups. INTERPRETATION: In patients with chronic hepatitis C, the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin. The benefit is mostly achieved in patients with HCV genotype 1 infections.

Adult↗
PubMed2001

Trovafloxacin hepatotoxicity.

A 19-year-old woman was treated for recurrent sinusitis with oral trovafloxacin and developed acute hepatitis and peripheral eosinophilia, with hepatosplenomegaly and ascites. Laparoscopic liver biopsy showed extensive centrilobular hepatocyte necrosis, likely causing venooclusive disease-like signs and symptoms. Clinical and laboratory abnormalities resolved completely after prolonged treatment with steroids. The temporal relationship between trovafloxacin and the onset of hepatitis favors this drug as a culprit.

Adult↗
PubMed2001

Predicting response to initial therapy with interferon plus ribavirin in chronic hepatitis C using serum HCV RNA results during therapy.

In patients with chronic hepatitis C, 48 weeks of therapy with interferon (IFN) plus ribavirin results in a sustained virologic response of 40%. Preliminary analysis suggests that measuring HCV RNA at week 24, rather than week 12, might provide the best prediction of treatment response. To assess the clinical utility of serum HCV RNA determinations at different times during therapy as a predictor of a sustained virologic response we evaluated 912 treatment-naïve patients. Patients were randomized to receive IFN-alpha2b, 3 million units (MU) three times weekly (tiw), for 24 or 48 weeks with either ribavirin or placebo, and then followed for 24 weeks. Serum HCV RNA was measured at weeks 4 and 12 in patients treated for 24 weeks; at 4, 12, and 24 weeks during therapy in those treated for 48 weeks, and week 24 post-therapy in all patients. Sustained response was defined as loss of serum HCV RNA at week 24 follow-up. Other patients were considered virologic nonresponders. For patients receiving 48 weeks of combination therapy, detectable serum HCV RNA at week 24 predicted nonresponse (positive predictive value) in 99% of patients compared to 89% at week 12. In patients treated for 24 weeks, testing at week 12 was more predictive of nonresponse than testing at week 4 in the combination-therapy group but not in the monotherapy group. Hence, for combination therapy, testing for serum HCV RNA as a predictor of nonresponse is most accurate at week 24 of therapy; a positive test correctly identified 99% of nonresponders.

Alanine Transaminase↗
PubMed2001

A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C.

This international, randomized, active-controlled, parallel-group, double-blind dose-finding study compared peginterferon alfa-2b (PegIntron) to interferon alfa-2b for the initial treatment of compensated chronic hepatitis C. We randomly assigned 1,219 subjects to receive either the standard three-times-weekly (TIW) interferon alfa-2b dose (3 MIU) or the once-weekly (QW) peginterferon alfa-2b (0.5, 1.0, or 1.5 microg/kg). Subjects were treated for 48 weeks and then followed for an additional 24 weeks. All 3 peginterferon alfa-2b doses significantly (P < or =.042) improved virologic response rates (loss of detectable serum HCV RNA) after treatment and after follow-up, as compared with interferon alfa-2b. Unlike the end-of-treatment virologic response, the sustained virologic response rate was not dose-related above 1.0 microg/kg peginterferon alfa-2b because of a higher relapse rate among patients treated with 1.5 microg/kg peginterferon alfa-2b, particularly among patients infected with genotype 1. All 3 peginterferon alfa-2b doses decreased liver inflammation to a greater extent than did interferon alfa-2b, particularly in subjects with sustained responses. No new adverse events were reported, and the majority of adverse events and changes in laboratory values were mild or moderate. In conclusion, peginterferon alfa-2b maintained (0.5 microg/kg) or surpassed (1.0, 1.5 microg/kg) the clinical efficacy of interferon alfa-2b while preserving its safety profile. The higher rate of virologic response during treatment with 1.5 microg/kg peginterferon alfa-2b in patients infected with genotype 1 and high viral levels warrants further evaluation.

Adult↗
PubMed2001

Assessment of hepatitis B virus DNA and hepatitis C virus RNA in the common bedbug (Cimex lectularius L.) and kissing bug (Rodnius prolixus).

OBJECTIVE: Historical clinical studies suggest the potential for insect-borne transmission of human hepatitis viruses. Studies of hepatitis B virus (HBV) persistence in insects were performed before the advent of molecular techniques, and studies to assess possible insect-borne transmission of hepatitis viruses have not yet been performed. The aim of this study was to determine, using molecular techniques, whether HBV and hepatitis C virus (HCV) persist in and are excreted in the feces of the bedbug Cimex lectularius L. and kissing bug Rodnius prolixus after an infectious meal. METHODS: Blood-feeding insects from the insect order Hemiptera (Cimex lectularius L. and Rhodnius prolixus) were fed on blood from infected patients with high titers of HBV, HCV, and control uninfected patients. Insects and insect excrement were collected at weekly intervals and tested for HBV DNA and HCV RNA using the polymerase chain reaction. RESULTS: HBV DNA was detected in bedbugs and excrement up to 6 wk after feeding on an infectious meal. HBV DNA was also detected in most kissing bugs and excrement up to 2 wk after feeding. HCV RNA was not detected in bedbugs at any time after feeding. CONCLUSIONS: We did not detect HCV RNA in bedbugs after feeding on an infectious meal. Our data provide molecular evidence to suggest that HBV may persist in Hemiptera. Additional studies are ongoing to determine whether this viral persistence is capable of infection.

Animals↗
PubMed2001

Transcription-mediated amplification is more sensitive than conventional PCR-based assays for detecting residual serum HCV RNA at end of treatment.

OBJECTIVE: In patients chronically infected with hepatitis C virus (HCV) undergoing antiviral therapy, sustained virologic response is suggested by viral clearance by end of treatment (EOT). Viral clearance is defined by nondetection of serum HCV RNA, usually by qualitative PCR-based assays with limits of detection ranging from 100 to 1000 copies/ml. However, some individuals relapse after achieving apparent viral clearance by EOT. These individuals may have low levels of viremia not detected by current PCR methods. The aim of this retrospective study was to determine whether the Bayer HCV RNA Qualitative Assay, which employs Transcription Mediated Amplification (TMA) and detects 50 HCV RNA copies/ml, could detect residual serum HCV RNA in patients who achieved apparent viral clearance by EOT and subsequently relapsed. METHODS: Samples were obtained at EOT (wk 24 or 48) and follow-up (wk 24-26 posttreatment) from 97 patients treated for HCV (78 relapsing patients, 19 sustained responders). All samples in which HCV RNA was not detected by PCR were tested in a blinded manner for HCV RNA by the TMA-based assay. RESULTS: HCV RNA was detected by the TMA-based assay in 27 (34.6%) EOT and 76 (97.4%) follow-up samples from relapsing patients, but not in any of the EOT or follow-up samples from sustained responders. CONCLUSION: Residual serum HCV RNA was detected by the TMA-based assay in EOT samples from 34.6% of patients that had achieved apparent viral clearance by PCR. The detection of HCV RNA by the TMA-based assay could help redefine EOT response and assist in the antiviral management of HCV infection.

Antiviral Agents↗
PubMed2001

Portal tract eosinophils and hepatocyte cytokeratin 7 immunoreactivity helps distinguish early-stage, mildly active primary biliary cirrhosis and autoimmune hepatitis.

We studied nondiagnostic liver biopsy specimens from 20 patients with definite primary biliary cirrhosis (PBC) and 18 with definite autoimmune hepatitis (AIH) to identify distinguishing features. All patients had early-stage disease; biopsy specimens were devoid of granulomas or diagnostic features of PBC or AIH. Diagnoses were based on serologic and clinical variables. Sixteen specimens from each group were immunostained with cytokeratin 7. The density of portal tract eosinophils and number with cytokeratin 7-reactive periportal hepatocytes were quantified. Sixteen of 18 patients with AIH and 13 of 20 with PBC had no or minimal bile duct injury. Histologic activity index scores were 5.8 in AIH and 5.7 in PBC. The mean portal eosinophil score was greater in PBC than in AIH. Cytokeratin 7 identified many central bile ducts that were obscured by portal inflammation. The mean periportal cytokeratin 7-reactive hepatocyte score was greater in PBC than in AIH. Portal eosinophils and cytokeratin 7 reactivity in periportal hepatocytes are supportive of PBC rather than AIH. No morphologic features were supportive of AIH. Cytokeratin 7 reactivity in periportal hepatocytes may be an early response to PBC-induced biliary obstruction in other regions of the liver.

Adult↗
PubMed2001

Current pharmacotherapy for hepatitis B infection.

Chronic infection with the hepatitis B virus (HBV) affects 350 million people worldwide, or approximately 5% of the global population, and commonly results in cirrhosis and hepatocellular carcinoma. Until recently, the only available treatment was injectable interferon alpha and response rates were suboptimal. Moreover, this expensive and toxic therapy had little applicability in the endemic regions of the world, i.e., Asia and Africa. The realisation that orally available nucleoside and nucleotide agents may effectively control this infection opened a new era in the management of chronic hepatitis B. Oral lamivudine recently became approved for treatment of hepatitis B worldwide. It is free of significant toxicity, improves liver histology and rapidly diminishes HBV DNA levels; lamivudine is expected to become the first-line therapy of choice. Nevertheless, the consistent emergence of lamivudine-resistant variants mandates the need to develop additional therapeutic agents. Adefovir dipivoxil, a nucleotide, and entecavir, a nucleoside agent, are promising new drugs that might eventually be used in combination with lamivudine and therefore reduce the incidence of drug resistance. There is a critical need to advance the research of hepatitis B antiviral agents so that effective combination therapies can become widely available.

Animals↗
PubMed2001

Treatment of viral hepatitis--2001.

Chronic viral hepatitis may now be controlled and, in many cases, permanently eradicated. Rapid advances in the antiviral therapy of chronic hepatitis C infection have resulted in a greater than 50% sustained response rate, with genotypes 2 and 3 now considered 'curable diseases.' Current hepatitis B therapy leads to significant improvement in liver histology and overall survival. These advances, coupled with the fact that 8% of the world population is chronically infected with viral hepatitis, has sparked considerable interest in this condition on the part of the pharmaceutical industry. In 2001, the most effective therapy for chronic hepatitis C is the combination of pegylated interferon alpha and oral ribavirin. The treatment of hepatitis B consists of either interferon alpha or oral lamivudine, while newer nucleoside/nucleotide analogues, alone or in combination with existing therapy, are being explored.

Antiviral Agents↗
PubMed2000

A comparison of the composition of epicuticular wax from red raspberry (Rubus idaeus L.) and hawthorn (Crataegus monogyna Jacq.) flowers.

Epicuticular waxes have been characterised from the flowers of raspberry and hawthorn, on both of which adult raspberry beetles (Byturus tomentosus) can feed. The flower wax from both species had similar alkane profiles and also contained long-chain alcohols, aldehydes and fatty acids. The range of the carbon numbers detected for these classes of compounds was broadly similar in both but the relative amounts of each differed between species. Raspberry flower wax also contained fatty acid methyl esters, a group of compounds that has rarely been detected in plant epicuticular waxes, however, these were not observed in hawthorn flower wax. Long-chain alcohol-fatty acid esters with carbon numbers ranging from C36 to C48 were also detected in both plant species. However, an examination of their constituent acids indicated that in hawthorn the esters based on the C16 fatty acid predominated, whilst in raspberry flower wax, esters based on the C20 fatty acid were most abundant. Both species also contained pentacyclic triterpenoids, which accounted for, on average, over 16 and 48% of the total wax extracted from raspberry and hawthorn flowers respectively. In the former, ursolic and oleanolic acids accounted for over 90% of the pentacyclic triterpenes, whilst hawthorn flower wax, in addition to containing these acids, also contained high relative concentrations of both free and esterified alpha- and beta-amyrins.

Alcohols↗
PubMed2000

The impact of interferon plus ribavirin on response to therapy in black patients with chronic hepatitis C. The International Hepatitis Interventional Therapy Group.

BACKGROUND & AIMS: Black patients with chronic hepatitis C have lower response rates than white patients to interferon monotherapy. The factors responsible for these differences are unknown, as is the impact of combination antiviral therapy on responsiveness among ethnic groups. We evaluated the impact of race on response to therapy in these patients. METHODS: A total of 1744 patients with chronic hepatitis C were randomized in 2 recent clinical trials to receive 24 or 48 weeks of interferon monotherapy or interferon-ribavirin combination therapy. RESULTS: Sustained virologic responses occurred in 27% of 1600 whites, 11% of 53 blacks (P = 0.01 vs. white), 44% of 32 Asians, and 16% of 27 Hispanics. No black patient had a sustained virologic response to interferon monotherapy, but 20% and 23% had sustained responses to 24 and 48 weeks, respectively, of combination therapy. Among black patients, 96% had hepatitis C genotype 1 compared with 65% of white subjects (P < 0.0001). Sustained response rates were similar for black and white patients with genotype 1 infection (23% vs. 22%, respectively). Compared with whites, black patients were older, weighed more, and had higher median Histologic Activity Index scores but did not differ in sex, baseline alanine aminotransferase or hepatitis C virus (HCV)-RNA levels, degree of fibrosis or percentage with cirrhosis, or other demographic variables. White subjects had a significantly greater reduction in HCV-RNA levels than blacks at weeks 4, 12, 24, and 48 of therapy, but only for black patients treated with interferon monotherapy. The decreased reduction of HCV-RNA reduction among blacks was eliminated by combination therapy. CONCLUSIONS: These observations suggest that the impaired responsiveness of black patients to interferon monotherapy can be overcome partially by combination interferon-ribavirin therapy.

Adult↗
PubMed2000

The significance of baseline serum alanine aminotransferase on pretreatment disease characteristics and response to antiviral therapy in chronic hepatitis C.

We sought to determine whether pretreatment serum alanine aminotransferase (ALT) levels in patients with chronic hepatitis C virus (HCV) correlate with demographic features and other disease characteristics and whether these values influence response to therapy. A total of 1,744 patients with HCV received either interferon alfa-2b and placebo or combination interferon alfa-2b and ribavirin for 24 or 48 weeks. Of these, 105 individuals (6%) had minimally raised serum ALT determinations at entry visit of </=1.3 x the upper limit of normal (ULN). By analysis of variance both pretreatment histologic activity index (HAI) scores (P <.0001) and fibrosis scores (P =.003) were significantly lower among patients with baseline ALT levels </=1.3 x ULN. Individuals with lower pretreatment ALT values were younger and weighed less than the ALT >1.3 x ULN cohort. Baseline ALT was not related to gender, race, baseline viral level, or HCV genotype. Using logistic regression analysis, the only demographic feature associated with ALT </=1.3 x ULN was lower baseline weight and lower baseline HAI score. There was no difference in sustained response between patients with baseline ALT levels </=1.3 x ULN and those with >1.3 x ULN, in all treatment groups (26 of 105, 24.8% for ALT </=1.3 x ULN; 440 of 1, 639, 26.8% for ALT >1.3 x ULN). We conclude that HCV patients with minimally raised ALT values (</=1.3 x ULN) weigh less, and have lower histologic inflammatory scores than patients with more conventionally elevated ALT levels. Despite these differences, these patients have a similar sustained response to antiviral therapy.

Adult↗
PubMed2000

A multicultural study of stereotyping in English-speaking countries.

Citizens of 9 different English-speaking countries (N = 619) evaluated the average, or typical, citizen of 5 English-speaking countries (Great Britain, Canada, Nigeria, United States, Australia) on 9 pairs of bipolar adjectives. Participants were drawn from Australia, Botswana, Canada, Kenya, Nigeria, South Africa, the United States, Zambia, and Zimbabwe. There were statistically significant similarities in the rankings of the 5 stimulus countries on 8 of the 9 adjective dimensions and a strong convergence of autostereotypes and heterostereotypes on many traits. The results relate to previous stereotyping research and traditional methods of assessing the accuracy of national stereotypes.

Australia↗
PubMed2000

Immunological responses in patients who have spontaneously eradicated hepatitis C virus infection.

We examined the proliferative responses of peripheral blood mononuclear cells obtained from 60 untreated patients who were seropositive by enzyme immunoassay, but negative for hepatitis C virus (HCV) RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). We used second- and third-generation recombinant immunoblot assay (RIBA) for further serological characterization. In vitro HCV-specific proliferative responses of mononuclear cells were compared to those of both untreated chronic HCV patients and patients who showed sustained virological response to interferon-alpha monotherapy, in order to assess the relative contribution of the immune response to the eradication of HCV. We found that frequency of responses to nonstructural proteins showed statistically significant differences, which were attributable to vigorous, polyspecific responses by cells from the RIBA-positive patients. In this group, core-specific proliferation was significantly associated with intravenous drug use as route of acquisition. Both other patient groups and the RIBA-indeterminate patients showed indistinguishable frequencies of proliferative responses. No association was detected between residual humoral responses, as determined from the RIBA results, and elapsed time since infection. The frequency of antibodies to NS5 differs between spontaneous cure and chronically infected patients. Cell-mediated and humoral immunity appear to be maintained in this population of patients.

Adolescent↗
PubMed2000

Tattoo application is not associated with an increased risk for chronic viral hepatitis.

OBJECTIVE: Many reports cite tattoo application as an independent risk factor for viral hepatitis. The purpose of this study was to determine whether patients with tattoos are at increased risk for chronic viral hepatitis. METHODS: A total of 212 patients, aged 18-55 yr, who presented to the emergency center and outpatient clinic at a suburban tertiary care hospital participated in the study. Of these, 106 had tattoos and 106 did not. No patient had known liver disease or viral hepatitis. Hepatitis B DNA, hepatitis C RNA, and hepatitis G RNA were measured in the serum using the polymerase chain reaction on stored serum samples. Each participant completed an anonymous questionnaire concerning risk factors for viral hepatitis. RESULTS: Patients with tattoos did not have a higher rate of chronic hepatitis B, C, or G than did a gender-matched group without tattoos. One (0.9%), seven (6.6%), and three patients (2.8%) in the tattoo group were positive for hepatitis B DNA, hepatitis C RNA, and hepatitis G RNA, respectively. Among controls, no patients (0%), three (2.8%), and six (5.6%) patients were positive for hepatitis B DNA, hepatitis C RNA and hepatitis G RNA, respectively (p = 0.815). All infected patients except one in each group reported a risk factor for viral hepatitis. Individuals with tattoos were more likely to have body piercing (p = 0.049; CI = 1.000-1.995), and more than five sexual partners (p = 0.013; CI = 1.073-1.846) than the control group. CONCLUSION: We find no evidence to support the observation that tattoos serve as a risk factor for chronic viral hepatitis.

Adolescent↗
PubMed2000

Minocycline as a cause of drug-induced autoimmune hepatitis. Report of four cases and comparison with autoimmune hepatitis.

We describe the clinical and liver biopsy morphologic features for 4 patients with minocycline-induced autoimmune hepatitis (group 1). We compared the serum laboratory values and liver biopsy findings from group 1 with those from 10 patients with sporadic autoimmune hepatitis (group 2). All patients in group 1 had positive serum antinuclear antibody titers, but none had positive serum anti-smooth muscle antibody titers. The morphologic findings of group 1 biopsies were those of autoimmune hepatitis in all 4 patients. In addition, 1 of these biopsy specimens also had scattered single eosinophils, unlike autoimmune hepatitis. The mean histologic activity index scores for patients in groups 1 and 2, respectively, were 6.7 and 5.4. No patients in group 1 had marked bridging fibrosis or cirrhosis, compared with 4 of 10 patients in group 2. Minocycline-induced autoimmune hepatitis is usually identical to sporadic autoimmune hepatitis. The absence of eosinophils does not exclude the possibility of a minocycline cause. In the absence of clinical or morphologic differences, a recent ingestion of minocycline should be excluded before the diagnosis of sporadic autoimmune hepatitis is established. Whether the drug is unmasking latent autoimmune hepatitis is unclear.

Adolescent↗