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Biomedical subjects

S C Gordon

Publications and source records attributed to S C Gordon.

At least 37 records · Page 2Linked to original sources

Antiviral therapy for chronic hepatitis B and C. Which patients are likely to benefit from which agents?

As primary care physicians become increasingly involved in diagnosis and treatment of patients with chronic viral hepatitis, an understanding of the antiviral options available, their limitations, and their side effects takes on a special importance. For chronic HBV infection, interferon alfa-2b requires only a 4-month course. However, it has adverse effects and contraindications and does not produce a universal response. Another option for HBV infection is lamivudine, which is administered orally and causes few side effects. However, relapse may occur when treatment is discontinued, and mutant virus may emerge. For chronic HCV infection, interferon alfa-2a, interferon alfa-2b, consensus interferon, and interferon combined with ribavirin have been used. The combination alternative is emerging as the method of choice in patients who do not have contraindications to oral ribavirin. Adverse effects are common, and durability of response varies according to HCV RNA level and genotype.

Antiviral Agents↗

Thymosin alpha1 treatment of chronic hepatitis B: results of a phase III multicentre, randomized, double-blind and placebo-controlled study.

Previous clinical trials have suggested that thymosin alpha1 (Talpha1), an immunomodulatory peptide, may be effective in the treatment of chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of Talpha1 in a multicentre, placebo-controlled and double-blind study of 97 patients with serum hepatitis B virus (HBV) DNA- and hepatitis B e antigen (HBeAg)-positive CHB. Patients who had been hepatitis B surface antigen (HBsAg) positive for at least 12 months entered a 3-month screening period prior to randomization. Forty-nine patients received Talpha1 (1.6 mg) and 48 patients received placebo, twice weekly for 6 months, and were followed-up for an additional 6 months. At inclusion, both groups were comparable for age, gender, histological grading, and aminotransferase and HBV DNA levels. A complete response to treatment, defined as a sustained serum HBV DNA-negative status (two negative results at least 3 months apart) during the 12-month study, with negative HBV DNA and HBeAg values at month 12, was seen in seven (14%) patients given Talpha1 and in two (4%) patients treated with placebo (P = 0.084). Five (10%) patients given Talpha1 and four (8%) patients given placebo exhibited a delayed response (defined as sustained serum HBV DNA negativity achieved after the 12-month study period with negative HBV DNA and HBeAg values at the last assessment). A total of 12 (25%) patients given Talpha1 and six (13%) patients given placebo showed a sustained loss of HBV DNA with a negative HBeAg value during or following the 12-month study period (P < 0.11). These results do not confirm observations of treatment efficacy reported in other clinical studies.

Adjuvants, Immunologic↗

The spatial distribution of larvae of Culicoides impunctatus biting midges.

The spatial distribution of Culicoides impunctatus Goetghebuer (Diptera: Ceratopogonidae) larvae was sampled at a site in western Scotland, and geostatistical analyses were used to quantify spatial dependencies. Nested sampling and analysis indicated that most of the spatial variance occurred within distances of 160-640 cm, levelling off at distances >640 cm. Semivariograms for transformed data from three 100 m x 100 m grids showed similar, isotropic patterns for larval counts, soil organic content, soil water content and the distribution of Juncus spp. rushes, with the variance increasing with separation distance. High levels of significance were associated with power models used to describe the semivariograms, which was indicative of the absence of a plateau (or 'sill') in the respective data. Correlation analysis of transformed data revealed significantly positive relationships between larval counts and soil pH, soil percentage organic content, soil percentage water content and also the distribution of Sphagnum spp., Juncus spp. and Myrica gale. There were also significantly negative relationships between larval counts and the distribution of Pteridium aquilinum and all mosses other than Sphagnum spp. The results suggest a far more structured and predictable pattern of C. impunctatus larval sites than previous studies and are discussed in relation to their application in localized Culicoides control and to studies of the mechanisms determining the spatial distribution of C. impunctatus larvae.

Animals↗

Serum alpha-fetoprotein levels in patients with chronic hepatitis C. Relationships with serum alanine aminotransferase values, histologic activity index, and hepatocyte MIB-1 scores.

Patients with chronic viral hepatitis and cirrhosis often have elevated serum alpha-fetoprotein (AFP) values, the causes of which are unclear. We studied 81 patients with chronic hepatitis C and the relationships of serum AFP and alanine aminotransferase (ALT) values, hepatic histologic features, and hepatocyte proliferation activity scores. Twenty-two patients had nil to mild fibrosis, 34 had moderate fibrosis, and 25 had marked fibrosis-cirrhosis. The mean serum AFP value was significantly greater in patients with more fibrosis. Serum ALT values were slightly greater in the marked fibrosis-cirrhosis patient group. The differences in the HAI and in hepatocyte MIB-1 scores were not significant. Among all patients, increasing serum AFP values significantly correlated with increasing ALT values. However, there were no significant correlations with serum ALT or HAI and serum AFP values. There was no association between serum AFP values and immunohistochemical staining for AFP within hepatocytes. These results suggest that elevated serum AFP values are the result of altered hepatocyte-hepatocyte interaction and loss of normal architectural arrangements. The presence of marked fibrosis or cirrhosis, a state of significant altered hepatocyte architecture, may be the underlying cause of increased serum AFP, rather than necrosis or active regeneration.

Alanine Transaminase↗

Factors contributing to the overuse of chemical pesticides in children with persistent head lice.

A growing number of head lice cases, for reasons that are not entirely clear, are repetitive or enduring. Despite the emerging phenomena, there has been little in the literature to guide school nurses in their day-to-day struggle with families experiencing head lice infestations that persist despite repeated treatment attempts. Children with persistent head lice are at increased risk of overexposure to chemical pesticides from multiple-treatment sources. In addition, school absences for persistent head lice infestations place children at risk educationally.

Animals↗

Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group.

BACKGROUND: Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS: We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy. RESULTS: The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interferon alone for either 24 weeks (13 of 231 patients, 6 percent) or 48 weeks (29 of 225 patients, 13 percent) (P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment). Among patients with HCV genotype 1 infection, the best response occurred in those who were treated for 48 weeks with interferon and ribavirin. Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks (57 percent) or 48 weeks (61 percent) than in those who were treated with interferon alone for either 24 weeks (44 percent) or 48 weeks (41 percent). The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy. CONCLUSIONS: In patients with chronic hepatitis C, initial therapy with interferon and ribavirin was more effective than treatment with interferon alone.

Adult↗

Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group.

BACKGROUND: Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy, but most subsequently relapse. We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS: We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment. A total of 173 patients were randomly assigned to receive standard-dose recombinant interferon alfa-2b concurrently with ribavirin (1000 to 1200 mg orally per day, depending on body weight) for six months, and 172 patients were assigned to receive interferon and placebo. RESULTS: At the completion of treatment, serum levels of hepatitis C virus (HCV) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone (82 percent vs. 47 percent, P<0.001). Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients (49 percent) in the combination-therapy group, but in only 8 patients (5 percent) in the interferon group (P<0.001). Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response. Base-line serum HCV RNA levels of 2 x 10(6) copies per milliliter or less were associated with higher rates of response in both treatment groups. Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group. Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone. CONCLUSIONS: In patients with chronic hepatitis C who relapse after treatment with interferon, therapy with interferon and oral ribavirin results in higher rates of sustained virologic, biochemical, and histologic response than treatment with interferon alone.

Adult↗

Clinical outcome of hepatitis C as a function of mode of transmission.

Several reports suggest that posttransfusion hepatitis C causes more aggressive histological activity than disease that is acquired via other routes. We sought to determine whether mode of transmission affects disease outcome. We studied the demographics, presenting laboratory data, and clinical course of 627 consecutively evaluated nonalcoholic patients with chronic hepatitis C. Two hundred eighty-two patients (45%) were transfusion recipients, 262 (42%) acquired the disease via other routes of percutaneous exposure, and 83 (13%) were without risks. Liver histology was available in 463 patients (215 transfusion recipients, 195 non-transfusion recipients, and 53 who were were without risks) and showed noncirrhosis in 274 (59%), cirrhosis in 173 (37%), and hepatocellular carcinoma in 16 patients (4%) who also had underlying cirrhosis. Duration of follow-up was 1 to 25 years (mean, 48 months; median, 21 years). One hundred eighteen of 173 (68%) cirrhotic patients were transfusion recipients; 40 of 173 (23%) cirrhotic patients acquired infection via other percutaneous exposure, and the remainder were without known risk factors (P < .001). Among the 215 patients with blood transfusions for whom histology was available, 118 of 215 (55%) had cirrhosis and 89 of 215 (41%) were noncirrhotic (P < .001); 8 transfused patients (4%) had hepatocellular carcinoma. In the percutaneous group, 40 of 195 (21%) of the patients were cirrhotic versus 153 of 195 (78%) who were noncirrhotic (P < .001); 2 patients (1%) had hepatocellular carcinoma. During the follow-up period, 59 of 189 (31%) of the cirrhotic patients (including those 16 individuals with hepatocellular carcinoma) developed hepatic decompensation. By univariate analysis, the risk of liver failure was related to age at viral acquisition, but by logistic regression analysis, only mode of transmission, and not age or estimated disease duration, predicted risk of liver failure. Patients with posttransfusion hepatitis C were more likely to develop decompensation than individuals who were not transfusion recipients (relative risk, 3.921; CI = 2.205 to 7.015). Serum albumin, prothrombin time, and platelet count at presentation were independent laboratory predictors of subsequent hepatic decompensation. The rate of hepatocellular carcinoma development among all cirrhotic patients during the follow-up period was 1.2% per year. Patients with posttransfusion hepatitis C are at greater risk of cirrhotic decompensation than those individuals with non-transfusion-acquired disease. The risk of liver failure is more closely related to the mode of transmission than to age at viral acquisition or to the duration of infection.

Adolescent↗

Sequential serum hepatitis C viral RNA levels longitudinally assessed by branched DNA signal amplification.

The aim of this study was to determine the stability of viral load over an extended period in patients with chronic hepatitis C virus (HCV). Sequential serum specimens collected from fourteen non-alcoholic adult patients with chronic HCV between 1990 and 1997 were tested retrospectively for HCV RNA levels by branched DNA assay (Quantiplex HCV RNA 2.0 [Chiron Diagnostics, Emeryville, CA]). A minimum of three serum samples was obtained at various intervals from each patient. None of the patients received antiviral therapy. Liver biopsies, available for 10 of 14 patients, showed mild or moderate hepatitis in seven and cirrhosis in three (one developed cirrhosis during follow-up). RIBA strip immunoassay showed that 7, 3, and 4 patients had viral genotypes 1, 2, and 3, respectively. The follow-up time averaged 5.3 years (range, 3.7 to 6.6 years). Eight patients (57.2%) showed increased viral levels from baseline to follow-up, the remaining six patients (42.8%) showed decreased viral levels. The three cirrhotic patients had the highest viral levels over time. The mean change was a 0.29-fold decrease (median, +1.14 [corrected]; range, -17.49 to +7.32). A less than twofold change in either direction was demonstrated for six patients (42.8%), and a less than threefold change was demonstrated for 10 patients (71.4%). Variation from baseline to last follow-up as calculated by log determination showed that the viremic load varied less than one log10 in all but one individual. These results show that viral load remains relatively stable over prolonged periods in most untreated patients with chronic hepatitis C.

Adult↗

Enhancing communication by using the Coordinated Care Classification System.

Because of the changes in our healthcare system, some clinical nurse specialists (CNSs) are having to expand their traditional roles of clinician, educator, consultant, leader, and researcher to include case management activities. The CNSs at Promina Gwinnett Health System in Lawrenceville, Georgia, have combined CNS and case manager activities and have adopted the title "CNS/Outcomes Coordinator." The CNS/Outcomes Coordinator is responsible for coordinating patient care, promoting team collaboration, and facilitating communication. To inform the healthcare team of the CNS/Outcomes Coordinator's patient responsibilities, the CNS/Outcomes Coordinators developed a Coordinated Care Classification System. This article describes how coordinating patient care, promoting team collaboration, and facilitating communication can be enhanced by the use of a classification system.

Adult↗

Serum alpha-fetoprotein levels and liver histology in patients with chronic hepatitis C.

OBJECTIVE: The clinical and morphological significance of a raised alpha-fetoprotein (AFP) level in patients with chronic hepatitis C is undefined. We sought to determine the relation between serum AFP level and liver histology in this population. METHODS: We reviewed the clinical and histological records of 200 consecutively evaluated patients with chronic hepatitis C whose serum AFP levels were recorded. Two groups were studied: group I = 125/200 (62%) patients with normal AFP, < 10 ng/ml; and group II = 75/200 (38%) patients with raised AFP, > 10 ng/ml. The groups were compared according to age, gender, duration of disease, histology, and history of alcohol abuse. RESULTS: There was no significant difference in serum AFP based on age, gender, alcohol consumption, or disease duration. Significant histological differences were observed: cirrhosis was present in 57 (45%) patients in group I versus 51 (68%) in group II (p < 0.001). Hepatocellular carcinoma was more frequent in group II (14/75 [19%]) than in group I (1/125 [1%]) (p < 0.001). Ten of 77 (13%) noncirrhotic patients and 51/108 (47%) cirrhotic patients had a raised AFP (p < 0.002; relative risk, 3.262; confidence interval [C.I.], 1.912-5.564). A derived AFP level of 17.8 ng/ml maximized specificity for predicting histological outcome: one of 76 (1.3%), 29/108 (26.8%), and 14/15 (93.3%) patients were noncirrhotic, cirrhotic, or had HCC, respectively. This derived AFP value is 35% sensitive and 98.6% specific for cirrhosis, with a positive predictive value of 97.7%. CONCLUSION: A serum AFP level >17.8 ng/ml strongly suggests the diagnosis of cirrhosis in a population of patients with chronic hepatitis C.

Aged↗

Treatment of chronic hepatitis C with interferon alfa-n3: a multicenter, randomized, open-label trial.

We studied the antiviral effectiveness and safety of interferon alfa-n3, a natural alpha interferon which contains multiple interferon species, in the treatment of previously untreated patients with chronic hepatitis C. Seventy-seven patients were randomized to receive either 1.0, 2.5, 5.0, or 10.0 million units (MU) of interferon alfa-n3 three times a week for 24 weeks and were then followed for an additional 24 weeks. At the end of therapy, 67% of patients in the 10 MU group normalized serum alanine transaminase (ALT) levels and 59% had no hepatitis C virus (HCV) RNA detected by polymerase chain reaction. At the end of the follow-up period, 44% of patients in the 10 MU group maintained normal ALT, and 24% had nondetectable HCV RNA. Lower doses were much less effective. Interferon alfa-n3 was well tolerated and no patient developed neutralizing anti-interferon antibodies during or after the treatment period. Interferon alfa-n3 appears to be effective against hepatitis C virus and deserves further study in larger randomized controlled trials.

Adult↗

Foreign body gingivitis: clinical and microscopic features of 61 cases.

Gingival inflammation associated with foreign bodies in connective tissue is termed foreign body gingivitis. It is not recognized commonly by clinicians and has not been described fully in the literature. This study examined the clinical and microscopic features of 61 cases of foreign body gingivitis. It was more common in women and occurred at a mean age of 48 years. It presented most frequently as a red or red and white painful chronic lesion that had been present for less than 1 year. Often it was diagnosed clinically as lichen planus. There was no gingival site predilection. Microscopically, foreign bodies, usually less than 5 microns in diameter, were found in an area of moderate to severe inflammation composed of lymphocytes, histiocytes, and plasma cells. The inflammation frequently was granulomatous and sometimes lichenoid.

Adolescent↗

Foreign body gingivitis: identification of the foreign material by energy-dispersive x-ray microanalysis.

Foreign bodies identified in 61 cases of foreign body gingivitis were analyzed by energy-dispersive x-ray microanalysis. This was compared with the energy-dispersive x-ray microanalysis of 62 dental materials. Comparative analysis indicated most foreign bodies were of dental material origin, usually abrasives. It is suggested that they are factitially and iatrogenically introduced during a variety of self-administered and professionally performed dental hygiene and restorative procedures. Individual elements, and elements by class, were correlated with previously described clinical and microscopic features of the cases. There was no association between any microscopic or clinical attribute of FBG and the presence of allergenic or cytotoxic elements. It is postulated that the physical presence of foreign bodies may be sufficient for the development of foreign body gingivitis. Dentists should be aware of the potential for chronic tissue damage that can result from the unguarded use of abrasive material next to the gingiva.

Adolescent↗

Comparative histologic features of liver biopsy specimens from patients coinfected with hepatitis G and C viruses with chronic hepatitis C virus alone: an age-, sex-, disease duration-, and transmission-matched controlled study of chronic hepatitis.

Hepatitis G virus (HGV) is a recently described, parenterally spread, positive-strand RNA virus of the Flaviviridae family. There is a high rate of HGV coinfection in patients with hepatitis C virus (HCV). Whether HGV can cause or is pathogenetically related to clinically apparent chronic liver disease, or whether HGV alters the course of hepatitis C in patients who are coinfected with both viruses is unknown. We studied 13 biopsy specimens from 11 patients coinfected with HGV and HCV and compared them with 15 biopsy specimens from a group of patients infected only with HCV who were matched for age, sex, disease duration, and transmission mode to characterize the histologic features of coinfected liver biopsy specimens and to look for any histologic features that might allow identification of coinfected patients. Three of the biopsy specimens from coinfected patients had a modified histologic activity index score of minimal chronic hepatitis, three of mild, two of mild/moderate, and five of moderate chronic hepatitis. Bile duct injury was absent in seven specimens, minimal in five, and mild in one. The biopsy specimens from patients who were coinfected with HGV and HCV had similar histologic features to the biopsy specimens of patients infected with HCV alone. There were no detectable histologic differences between the biopsy specimens from the two patient groups. The P values for the statistical comparisons confirmed this impression. In addition, no group of histologic features distinguished the coinfected patient group from the control group. Any suspicion that a clinician might have about the presence of HGV requires confirmation by reverse transcriptase-polymerase chain reaction testing of serum samples. Our results suggest that HGV most likely does not actively participate in the cytotoxic effects of chronic hepatitis or does so by a mechanism as yet undefined. Although HGV can cause chronic infection, the present study provides no evidence that it causes or contributes to chronic hepatitis.

Biopsy↗

Alfa interferon treatment of hepatitis C virus RNA-positive patients with normal or near-normal alanine aminotransferase levels.

OBJECTIVES: Alfa interferon therapy is conventionally offered only to chronic hepatitis C patients with abnormal serum alanine aminotransferase (ALT) values. Therapeutic response is traditionally gauged by normalization of liver enzymes. Treatment of patients with persistently normal serum aminotransferases is not routinely done. The purpose of this study was to determine whether standard therapy with alfa interferon can eradicate hepatitis C virus in viremic patients with persistently normal or near-normal serum aminotransferases. METHODS: Between 1990 and 1996 we evaluated 565 patients with chronic hepatitis C. Of these, 49 patients (8.7%) (15 men, 34 women) had normal or near-normal ALT levels (less than 1.5 times upper limit of normal) for at least 3 consecutive months. Of these, 15 patients were studied. Treatment consisted of interferon alfa-2b 3 million units thrice weekly for 6 months. RESULTS: Normal or near normal ALT levels are more common in women than men. All patients completed 6 months of therapy, and 12 patients completed 6 months of posttreatment follow-up. Only one patient lost hepatitis C virus RNA during treatment and viremia reappeared in this patient immediately after cessation of therapy. CONCLUSIONS: Standard antiviral therapy of patients with normal or near-normal ALT levels does not result in sustained viral eradication in most patients.

Alanine Transaminase↗

Experimental evidence against replication or dissemination of hepatitis C virus in mosquitoes (Diptera:Culicidae) using detection by reverse transcriptase polymerase chain reaction.

In 3 laboratory experiments, mosquitoes were fed hepatitis C virus (HCV)-RNA positive blood by using membrane feeders, separated into head, thorax, and abdomen, and tested by a reverse transcriptase polymerase chain reaction for HCV-RNA. HCV did not replicate or disseminate in mosquitoes that had ingested blood from patients that were HCV-viremic positive. When yellow fever mosquitoes, Aedes aegypti (L.), were held for 1, 3, 7, 14, and 21 d after feeding, HCV-RNA was detected in the abdomens of 5/5 mosquitoes at 1 d after feeding; remaining tissues were negative with the exception of a single positive head at 7 d. In agreement, HCV-RNA was detected in Asian tiger mosquito, Aedes albopictus Skuse, and Anopheles stephensi Liston abdomens at 1 d, but not 3 d after feeding no HCV-RNA was detected in heads or thoraces. In addition, HCV-RNA was detected in heads of Ae. aegypti at 10 and 20 min, but not at 30 min, after feeding. The latter results raise the possibility of HCV contamination of mouthparts and, theoretically, mechanical transmission of this virus.

Aedes↗