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Biomedical subjects

R P Myers

Publications and source records attributed to R P Myers.

At least 19 recordsLinked to original sources

Management of chronic hepatitis C in French departments of internal medicine and infectious diseases.

This prospective, multicentre study was conducted during 2-30 April 2001 in the internal medicine/infectious diseases services in France and included data from 1858 hepatitis C virus (HCV)-infected patients, half of whom were HIV co-infected. The aims were to outline the type of pre-therapeutic evaluation of HCV infection performed (HCV RNA, genotype, liver biopsy); determine the proportion and characteristics of patients receiving antiviral treatment; and determine if any changes in these parameters had occurred between 1995 and 2001. Patients whom had a complete pre-therapeutic evaluation (39%, 709/1834) and received antiviral treatment (38%, 690/1830) were more likely to have abnormal liver biochemistry, cirrhosis and cryoglobulinaemia (P < 0.001). Injecting drug users and HIV-co-infected patients were less likely to have a complete pre-therapeutic evaluation or receive antiviral treatment (P < 0.001). A complete pre-therapeutic evaluation was more often performed in 2001 than in 1995 (39% vs. 6%, P < 0.001), including qualitative HCV RNA testing (91% vs. 68%, P < 0.001), genotyping (59% vs. 7%, P < 0.001) and a liver biopsy (60% vs. 29%, P < 0.001). The frequency of anti-HCV treatment approximately doubled between 1995 and 2001 (20% vs. 38%, P < 0001). Although adherence to consensus recommendations regarding pre-therapeutic evaluation is not ideal, a substantial improvement has occurred since 1995. Nevertheless, means of increasing the availability of antiviral therapies, particularly for patients with HIV co-infection or injecting drug use, require further study.

Adult↗

Silymarin treatment of viral hepatitis: a systematic review.

Silymarin from the milk thistle herb (Silybum marianum) is used by many patients with chronic viral hepatitis, but its efficacy remains unknown. We performed a systematic review of silymarin for the treatment of chronic viral hepatitis B and C. An exhaustive search strategy identified 148 papers that studied silymarin compounds in liver disease. Of these, four trials included patients with hepatitis C, one included hepatitis B patients, and two, unspecified chronic viral hepatitis. However, only one trial exclusively studied patients with hepatitis C, and none involved patients with only hepatitis B. Silymarin treatment resulted in a decrease in serum transaminases compared with baseline in four studies, and compared with placebo in only one study. There is no evidence that silymarin affects viral load or improves liver histology in hepatitis B or C. No studies were found that investigated the use of silymarin concomitantly with interferon, nucleoside analogues, or other conventional treatments for hepatitis B or C. In conclusion, silymarin compounds likely decrease serum transaminases in patients with chronic viral hepatitis, but do not appear to affect viral load or liver histology. Nevertheless it may be worthwhile to determine its effects in conjunction with standard antiviral treatment.

Clinical Trials as Topic↗

The rate of fibrosis progression is an independent predictor of the response to antiviral therapy in chronic hepatitis C.

The response to antiviral therapy and the rate of fibrosis progression in chronic hepatitis C virus (HCV) infection are related to common factors, including age and gender. The aim of this study was to evaluate the relationship between the rate of fibrosis progression and the sustained virologic response (SVR) to interferon (IFN)-based treatment. A total of 332 patients treated for chronic HCV infection were evaluated. Using multivariate logistic regression analysis, the impact of the rate of fibrosis progression (defined as the stage of liver fibrosis according to the Metavir system/duration of infection) on the rate of SVR (negative HCV RNA at least 6 months following the end of treatment), was determined. The median age of the patients was 44 (range 25-77) years, 64% were male, and 66% were infected with genotypes 1, 4, 5 or 6. The median rate of fibrosis progression was 0.083 (range 0-2) Metavir units/year; 158 patients (48%) had F2-F4 fibrosis. After a median of 48 (range 2-126) weeks of therapy (IFN, n=190; IFN and ribavirin, n=96; pegylated IFN, n=20; pegylated IFN and ribavirin, n=26), 93 patients (28%) achieved an SVR. In univariate analysis, the rate of SVR was higher in slow [< 0.083 Metavir units/year (n=162)] than rapid progressors [> or = 0.083 Metavir units/year (n=170)] (35%vs 22%, P=0.01). After controlling for age, gender, genotype, viral load, and treatment regimen and duration, the rate of fibrosis progression remained an independent predictor of SVR (slow vs rapid progressors, OR 2.74; 95% CI 1.27-5.92; P=0.01). Hence the rate of fibrosis progression is an independent predictor of SVR to IFN-based therapy in patients with chronic hepatitis C. This additional factor should be considered in economic models evaluating this condition.

Adult↗

The impact of prior hepatitis B virus infection on liver histology and the response to interferon therapy in chronic hepatitis C.

Patients with chronic hepatitis C frequently have antibodies to the hepatitis B core antigen (anti-HBc), indicative of prior hepatitis B virus (HBV) infection. In these patients, persistence of HBV may exacerbate liver injury and diminish the response to treatment. The aim of this study was to evaluate the relationship between previous HBV infection and liver histology and the sustained virologic response (SVR) to interferon (IFN)-based therapy in patients with chronic hepatitis C. A total of 132 HBsAg-negative, treatment-naive patients were evaluated. Using multiple logistic regression analysis, the impact of anti-HBc-positivity on the rate of SVR was determined. Progression to bridging fibrosis or cirrhosis was assessed using Cox proportional hazards regression and Kaplan-Meier survival analysis. The median age of the patients was 47 years (IQR, 37-60), 57% were male, and 73% had genotypes 1, 4, 5, or 6. Fifty-one patients (39%) were anti-HBc-positive. The prevalence of moderate to severe necroinflammatory activity (P = 0.36) and progression to bridging fibrosis or cirrhosis (log-rank P = 0.83) was similar between anti-HBc-positive and -negative patients. After a median of 48 weeks (IQR, 26-52) of therapy (IFN, n = 116; IFN and ribavirin, n = 16), 23 patients (17%) achieved a SVR; the rate of response was similar in anti-HBc-positive and -negative patients (18%vs 17%, P = 1.00). After controlling for age, gender, genotype, fibrosis, and treatment regimen, anti-HBc status did not independently affect the rate of SVR (anti-HBc-positive vs negative: odds ratio, 1.36; 95% confidence interval, 0.45 to 4.06; P = 0.58). In conclusion, previous HBV infection does not affect liver histology or the response to IFN-based therapy in patients with chronic hepatitis C.

Adult↗

Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial.

Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.

Adolescent↗

Interferon for acute hepatitis C.

BACKGROUND: Acute hepatitis C virus (HCV) infection progresses to chronicity in the majority of patients. In order to prevent the progression to chronic disease, several studies have assessed interferon in patients with acute hepatitis C. OBJECTIVES: The aim of this review was to assess the efficacy of interferon in acute HCV infection. SEARCH STRATEGY: We searched MEDLINE, the Cochrane Controlled Trials Register, and the abstracts of the American Association for the Study of Liver Diseases (June 2001). We also contacted pharmaceutical companies to obtain unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo or no treatment, and published as an article, abstract, or letter were selected. No language limitations were used. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. The following endpoints were analysed: normalization of alanine aminotransferase (ALT) activity at the end of treatment (biochemical ETR); sustained ALT normalization at the end follow-up (biochemical SR); disappearance of serum HCV RNA by polymerase chain reaction assay at the end of treatment (virologic ETR) and at the end of follow-up (virologic SR). Histologic data and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS: Six randomised trials involving 206 patients with acute hepatitis C met the inclusion criteria. Four trials assessing interferon alfa-2b in 141 patients, all with transfusion-acquired acute hepatitis C, were included. They demonstrated no significant heterogeneity in the outcomes assessed. When compared with no treatment, interferon alfa-2b was associated with an increase in the rates of virologic ETR and SR by 45% (95% CI 31-59%, P < 0.00001) and 29% (95% CI 14-44%, P = 0.0002), respectively. The virologic ETR was 42% (95% CI: 30-56%) in the interferon alfa-2b group versus 4% (95% CI 0-13%, P < 0.00001) in the control group. At the end of follow-up, a virologic SR was seen in 32% (95% CI 21-46%) of interferon-treated patients versus only 4% (95% CI 0-13%, P = 0.00007) of controls. The tolerability of therapy, or the impact of interferon alfa-2b on hepatic histology, was not reported. Two trials assessed interferon beta in a total 65 patients. The efficacy of interferon beta could not be assessed, however, due to heterogeneity of these trials. REVIEWER'S CONCLUSIONS: Interferon alfa is effective in improving biochemical outcomes and achieving sustained virologic clearance in patients with transfusion-acquired acute hepatitis C. The effect on long-term clinical outcomes could not be assessed due to limitations in the current data.

Acute Disease↗

Interferon for interferon naive patients with chronic hepatitis C.

BACKGROUND: A previous meta-analysis of interferon therapy in naive patients with chronic hepatitis C has documented its efficacy in achieving virologic clearance, and improving liver biochemistry and histology; however, since its publication additional trials have been reported. OBJECTIVES: To evaluate the response to interferon in interferon naive patients with chronic hepatitis C. The effect of treatment dose and duration, and the response in patients with cirrhosis and those with normal aminotransferases was also investigated. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Cochrane Library Issue 1, 1999), MEDLINE (January 1966 to December 1999), and reference lists were searched, and pharmaceutical companies were contacted for unpublished trials. SELECTION CRITERIA: Randomised clinical trials comparing interferon with placebo, no treatment, or different regimens of interferon were selected. Abstracts were excluded. DATA COLLECTION AND ANALYSIS: The primary outcome measure was sustained disappearance of serum HCV RNA (virologic sustained response (SR)). Biochemical and end of treatment responses, liver histology, and adverse events were also recorded. Assessment of drug efficacy used the methods of Peto and Der Simonian and Laird. MAIN RESULTS: Fifty-four trials enrolling 6545 patients were included. Compared with no treatment, interferon 3 MU thrice weekly for 12 months increased the probability of a virologic SR (Peto odds ratio (OR) 4.60; 95% confidence interval (CI) 1.53 to 13.85). At this dosage and duration of therapy, the rate of virologic SR was 17% (95% CI 10 to 28%) in interferon-treated patients versus 3% (95% CI 1 to 10%) in controls. A dose of 6 MU was more effective than 3 MU thrice weekly (OR for 12 months treatment, 2.21; 95% CI 1.10 to 4.45), as were durations of 12 months or greater versus six months (OR 1.87; 95% CI 1.30 to 2.67). Adverse events were more common with higher doses and prolonged durations of treatment. Compared with no therapy, interferon increased the probability of histologic improvement (OR 9.22; 95% CI 5.69 to 14.94). The response to interferon in cirrhotic patients (virologic SR, 17%; 95% CI 11 to 26%) was similar to that in non-cirrhotic patients. However, interferon was no more effective than control in patients with normal aminotransferases. REVIEWER'S CONCLUSIONS: Interferon is effective in achieving viral clearance and improving liver biochemistry and histology in interferon naive patients with chronic hepatitis C. Higher doses and prolonged durations are more effective, but associated with more frequent adverse events. Interferon is associated with similar benefits in patients with cirrhosis, but the efficacy in patients with normal aminotransferases is unproven.

Antiviral Agents↗

Interferon for interferon nonresponding and relapsing patients with chronic hepatitis C.

BACKGROUND: Interferon monotherapy leads to sustained virologic clearance in a minority of patients with chronic hepatitis C. Studies have yielded conflicting results regarding retreatment with interferon in nonresponders and relapsers. OBJECTIVES: To assess the beneficial and harmful effects of retreatment with interferon in chronic hepatitis C nonresponders and relapsers to previous interferon treatment. SEARCH STRATEGY: Trials were identified through electronic databases, manual searches, authors, and pharmaceutical companies (August 2001). SELECTION CRITERIA: Randomised trials comparing interferon versus control or different interferon regimens in chronic hepatitis C patients being nonresponders and relapsers to previous interferon were included. DATA COLLECTION AND ANALYSIS: The primary outcome was failure to achieve a sustained virologic response defined as positive serum hepatitis C virus RNA at least six months following treatment. Secondary outcomes included liver-related morbidity, mortality, biochemical responses, adverse events, and histology. MAIN RESULTS: Ten randomised trials involving 686 nonresponders and eight trials involving 484 relapsers were included; their methodological quality was poor. In nonresponders, interferon reduced the risk of not achieving an end of treatment biochemical response compared with no treatment (relative risk [RR] 0.77, 95% confidence interval [CI] 0.66 to 0.91); however, virologic responses were not reported. In a post hoc subgroup analysis, doses greater than 3 million units (MU) three times weekly offered no advantage compared with 3 MU three times weekly for biochemical sustained response. Failure to obtain a virologic sustained response was less likely with 48 than 24 weeks of therapy (RR 0.87, 95% CI 0.79 to 0.96). Adverse events did not differ significantly regardless of treatment dose or duration. In relapsers, none of the trials compared interferon with no treatment. In a post hoc analysis, doses greater than 3 MU three times weekly were no more effective in achieving a virologic sustained response than 3 MU three times weekly. Compared with 24 weeks, treatment durations of 48 weeks were less likely to fail to achieve a virologic sustained response (RR 0.69, 95% CI Random 0.51 to 0.95), but associated with more frequent dosage reduction (RR 9.07, 95% CI 1.20 to 68.63). No data regarding clinical outcomes or histology was available in either patient group. REVIEWER'S CONCLUSIONS: Retreatment with interferon leads to sustained virologic clearance in a minority of chronic hepatitis C patients with nonresponse or relapse following interferon monotherapy. Treatment durations of 48 weeks are superior to 24 weeks, but doses greater than 3 MU three times weekly are no more effective. No data exists regarding the effect on clinical outcomes.

Antiviral Agents↗

Fatigue in patients with chronic hepatitis C.

In numerous studies of symptoms in patients with chronic hepatitis C there has been no systematic assessment of both fatigue and extrahepatic manifestations. Our objective was to assess the prevalence of fatigue in patients with hepatitis C virus (HCV) infection, and to identify associations between fatigue and clinical and biological hepatic and extrahepatic manifestations. We studied 1614 patients. Data were prospectively recorded during the first visit of patients infected with HCV and the prevalence of fatigue and its association with dermatological, rheumatological, neurological and nephrological manifestations; diabetes; arterial hypertension; auto-antibodies, and cryoglobulinaemia were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunological, virological, and histological factors associated with the presence of fatigue. Fatigue was present in 53% of patients (95% confidence interval 51-56). In 17% of patients (95% confidence interval 15-19) fatigue was severe, impairing activity. Five other extrahepatic manifestations had a prevalence above 10% including, in decreasing order: arthralgia, paresthesia, myalgia, pruritus, and sicca syndrome. In univariate and multivariate analyses, fatigue, in comparison with the absence of fatigue, was associated with female gender, age over 50 years, cirrhosis, depression and purpura. Independent of these associations, fatigue was associated with arthralgia, myalgia, paresthesia, sicca syndrome and pruritus. The prevalence of fibromyalgia (as defined by the association of fatigue with arthralgia or myalgia) was 19% (95% confidence interval 17-21). There was no significant association between fatigue and the following characteristics: viral load or genotype, alcohol consumption, abnormal thyroid function, and type and level of cryoglobulinaemia. Hence, fatigue is the most frequent extrahepatic manifestation in patients infected with HCV. Fatigue is independently associated with female gender, age over 50 years, cirrhosis, depression and purpura.

Adolescent↗

Predicting prostate carcinoma volume and stage at radical prostatectomy by assessing needle biopsy specimens for percent surface area and cores positive for carcinoma, perineural invasion, Gleason score, DNA ploidy and proliferation, and preoperative serum prostate specific antigen: a report of 454 cases.

BACKGROUND: DNA ploidy analysis of prostate carcinoma is a generally accepted prognostic marker, particularly when tumors are extraprostatic at the time of surgery. In the past decade, the DNA content of prostate carcinoma frequently has been assessed in needle biopsy specimens based on the assumption that ploidy, in conjunction with serum prostate specific antigen (PSA) and Gleason score, provides valuable pretreatment information. METHODS: Between 1995 and 1998, the authors identified a consecutive series of 454 prostate carcinomas, verified by needle biopsies and followed by radical retropubic prostatectomies (RRP). Based on the needle biopsies, DNA ploidy and MIB-I immunostaining were measured by digital image analysis (DIA). The authors also quantified the percent of nuclei in four categories from the DNA histograms. The DIA data were combined with the age of the patient at diagnosis, the serum PSA, Gleason score, percent cores and percent surface area positive for carcinoma, and status of perineural invasion in multivariate models using tumor volume and risk of extraprostatic extension (EPE) at RRP as the outcome variables. RESULTS: Joint predictors of tumor volume at RRP were the percent cores positive for carcinoma (P < 0.0001), serum PSA (P < 0.0001), the percent surface area positive for carcinoma (P < 0.0001), and the percent nuclei classified by DNA quantification to be in the "S-phase" category (P = 0.03). Joint predictors of risk of EPE were the percent cores positive for carcinoma (P = 0.0004), a Gleason score of 7 (P < 0.0001), a Gleason score of 8 or 9 (P < 0.0001), serum PSA (P = 0.006) and perineural invasion (P = 0.02). CONCLUSIONS: After adjusting for traditional prognostic markers, DNA ploidy interpretation and MIB-I quantitation of prostate carcinoma did not appear to jointly predict either outcome variable in the multivariate models. However, a quantitative measure related to both ploidy and proliferation, the percent of nuclei in the putative "S-phase" category from the DIA histograms, was found to jointly predict for tumor volume.

Adult↗

Nitric oxide donors regulate nitric oxide synthase in bovine pulmonary artery endothelium.

This study examined the notion that exogenous generation of nitric oxide (NO) modulates NOS gene expression and activity. Bovine pulmonary artery endothelial cells (BPAEC) were treated with the NO donors, 1 mM SNAP (S-nitroso-N-acetylpenicillamine), 0.5 mM SNP (sodium nitroprusside) or 0.2 microM NONOate (spermine NONOate) in medium 199 containing 2% FBS. Controls included untreated cells and cells exposed to 1 mM NAP (N-acetyl-D-penicillamine). NOS activity was assessed using a fibroblast-reporter cell assay; intracellular Ca2+ concentrations were assessed by Fura-2 microfluorometry; and NO release was measured by chemiluminescence. Constitutive endothelial (e) and inducible (i) NOS gene and protein expression were examined by northern and western blot analysis, respectively. Two hours exposure to either SNAP or NONOate caused a significant elevation in NO release from the endothelial cells (SNAP = 51.4 +/- 5.9; NONOate = 23.8 +/- 4.2; control = 14.5 +/- 2.8 microM); but A23187 (3 microM)-stimulated NO release was attenuated when compared to controls. Treatment with either SNAP or NONOate for 2 h also resulted in a significant increase in NOS activity in endothelial homogenates (SNAP = 23.6 +/- 2.5; NONOate= 29.8 +/- 7.7; control = 14.5 +/- 2.5fmol cGMP/microg per 10(6) cells). Exposure to SNAP and SNP, but not NONOate, for 1 h caused an increase in intracellular calcium. Between 4 and 8 h, SNAP and NONOate caused a 2- to 3-fold increase in eNOS, but not iNOS, gene (P < 0.05) and protein expression. NAP had little effect on either eNOS gene expression, activity or NO production. Our data indicate that exogenous generation of NO leads to a biphasic response in BPAEC, an early increase in intracellular Ca2+, and increases in NOS activity and NO release followed by increased expression of the eNOS gene, but not the iNOS gene. We conclude that eNOS gene expression and activity are regulated by a positive-feedback regulatory action of exogenous NO.

Animals↗

Efficacy of first-generation Cavermap to verify location and function of cavernous nerves during radical prostatectomy: a multi-institutional evaluation by experienced surgeons.

OBJECTIVES: To evaluate, using five experienced surgeons, the efficacy of the first-generation Cavermap Surgical Aid to identify the cavernous nerves intraoperatively and to predict the recovery of sexual function. This study was not designed to determine whether this device improves the ability to preserve the nerves or improve outcome. METHODS: Fifty men younger than 60 years old (mean age 52.5 years; range 43 to 59) with clinically localized prostate cancer (76% T1c, mean Gleason score 6, prostate-specific antigen level less than 10 ng/mL) underwent nerve-sparing radical prostatectomy (90% bilateral). Intraoperatively, the Cavermap device was used to test for the presence of the cavernous nerves once the neurovascular bundle was identified visually and to determine whether the nerves were intact after the prostate was removed. Erectile function was evaluated using the International Index of Erectile Function; men were considered potent if they were able to achieve unassisted intercourse in at least one half of their attempts. RESULTS: Before the removal of the prostate, the tumescence response to stimulation of the neurovascular bundle was 87.8%; when tissue not containing the neurovascular bundle was stimulated, no tumescence response occurred in 54%. After prostatectomy, a bilateral response to stimulation occurred in 90%, a unilateral response in 5%, and no response in 5%. Postoperatively, 71% of the patients were potent at 12 months. In the patients who demonstrated bilateral stimulation after removal of the prostate, 78% were potent at 12 months. CONCLUSIONS: After radical prostatectomy performed by experienced surgeons, patient-reported potency rates in men younger than 60 years of age were high. Cavermap stimulation demonstrated an 87.8% sensitivity and 54% specificity in locating the neurovascular bundle as identified by experienced surgeons. The lack of specificity of this first-generation device limits its application for deciding which structures can be safely preserved or excised. Because virtually all patients demonstrated a positive response after removal of the prostate, the value of stimulation to predict the recovery of sexual function is yet to be determined.

Adult↗

Practical surgical anatomy for radical prostatectomy.

Practical guidelines in surgical anatomy for radical prostatectomy can be summarized as follows: 1. There is significant individual variation in the anatomy of the male pelvis. 2. The prostate is covered anteriorly by a prominent detrusor apron. 3. Prostates vary with respect to size and shape. 4. BPH compresses and flattens the peripheral zone. 5. In reality, the puboprostatic ligaments are pubovesical ligaments. 6. The dorsal vein complex of the penis is a neurovascular plexus of veins, arteries, and nerves situated primarily ventral to the prostate and urethra. 7. The urethra from the verumontanum to the penile bulb is sphincteric, with its smooth muscle and elastic tissue components primarily responsible for postprostatectomy urinary continence. 8. Multiple micropedicles tether the neurovascular bundles along the entire posterolateral aspect of the prostate.

Anal Canal↗

Historical features are poor predictors of liver fibrosis in Canadian patients with chronic hepatitis C.

The progression of fibrosis in chronic hepatitis C infection (HCV) is related to host factors including age, gender and alcohol consumption. Due to the morbidity and potential mortality of liver biopsy, a noninvasive method of assessing hepatic fibrosis is needed. The aim of this study was to assess the utility of historical features in predicting fibrosis using published rates of fibrosis progression. The charts of 239 untreated patients with HCV were reviewed; patients who had a liver biopsy and whose duration of infection could be estimated (n=106) were categorized according to gender, age at infection (< or = or > 40 years) and peak alcohol consumption (< or > or = 50 g/day). Estimates of fibrosis were calculated using the product of the interval between infection and biopsy and published rates of fibrosis progression. Estimates were compared with liver biopsies staged according to the Metavir system (F0-F4; F0=no fibrosis; F4= cirrhosis). The mean age of patients was 42 +/- 8 years, 61% were male and 36% consumed > 50 g of alcohol daily. The mean duration of infection was 19 +/- 9 years (range, 1-40) and ALT was elevated > 1.5 times upper normal in 63%. When patients were classified into those with mild (F0-F2) and severe (F3-F4) fibrosis, the sensitivity, specificity, positive predictive value and negative predictive value of an estimate of mild fibrosis was 60%, 55%, 78% and 34%, respectively. An estimate of severe fibrosis had a sensitivity of 55%, specificity of 60%, positive predictive value of 34% and negative predictive value of 78%. Agreement between fibrosis estimates and actual histological stages was poor (kappa = 0.13, P=0.08). The prediction of hepatic fibrosis in HCV infection using historical features and published rates of fibrosis progression is poor in a Canadian clinical practice setting. Alternate noninvasive methods of predicting hepatic fibrosis are needed.

Adult↗

Radical prostatectomy: making it a better operation in the new millennium.

Radical prostatectomy provides the best hope for long-term survival, free of disease, for organ-confined adenocarcinoma of the prostate. The operation is performed successfully only by understanding the remarkable anatomic variability of the prostate apex and the cylindrical nature of the striated urethral sphincter. When surgical techniques are used that take into account variations at the apex, with preservation of (i) neurovascular structures; (ii) the sphincteric urethra; and (iii) the adjacent levator ani, patients can look forward to a cure and the rapid return of urinary control and erectile function.

Humans↗

Acute interstitial nephritis due to omeprazole.

Omeprazole is a proton pump inhibitor that is used commonly in the treatment of acid-peptic disorders. Although omeprazole is generally well tolerated, serious adverse effects such as renal failure have been reported. Thus far, 17 cases of acute interstitial nephritis (AIN) secondary to omeprazole have been described. Another case of AIN is described in a 36-yr-old woman presenting with nausea, vomiting, weight loss, and a rising serum creatinine concentration. Omeprazole therapy had ceased 2 wk before admission. AIN was diagnosed by renal biopsy and corticosteroid therapy was initiated. After 4 wk of therapy the serum creatinine concentration had normalized. Among the reported cases in the literature, AIN was diagnosed after an average of 2.7 months of therapy with 20-40 mg of omeprazole daily. Recurrence was universal on rechallenge. Common symptoms included fatigue, fever, anorexia, and nausea. The classic triad of fever, rash, and eosinophilia was uncommon. Typical laboratory features included hematuria, proteinuria, pyuria, eosinophilia, and anemia. Management consisted of withdrawal of omeprazole and corticosteroid therapy in some patients. All but one patient recovered normal renal function. Corticosteroid therapy was well tolerated and may have been beneficial.

Acute Disease↗

Reactivation of hepatitis B e antigen-negative chronic hepatitis B in a bone marrow transplant recipient following lamivudine withdrawal.

Reactivation of hepatitis B virus (HBV) is a recognized complication of bone marrow transplantation (BMT). Lamivudine is a nucleoside analogue with potent antiviral activity that has been used in the prophylaxis of HBV reactivation in at-risk BMT recipients. Currently, no data exist regarding the safety of nucleoside analogue withdrawal in these patients. A 32-year-old BMT recipient with hepatitis B e antigen (HBeAg)-negative, chronic HBV who developed a serious flare of hepatic inflammation due to a rebound in viral replication within 12 weeks of discontinuing lamivudine therapy is described. The patient remained HBeAg-negative despite high level viremia, suggesting the emergence of a mutant viral strain. The patient's acute hepatitis resolved promptly with the reinstitution of lamivudine therapy. Further studies are necessary to define the safety and efficacy of nucleoside analogues in the prevention of HBV reactivation in at-risk BMT recipients. Clinicians should consider the risk of inducing serious flares of hepatic inflammation due to abrupt nucleoside analogue withdrawal in these patients.

Adult↗

Multiple focal nodular hyperplasia and steatosis: Atypical imaging characteristics.

Focal nodular hyperplasia is a rare, benign condition of the liver. A 28-year-old woman with malignant melanoma, mild liver enzyme abnormalities, steatohepatitis and newly documented hepatic lesions is described. Ultrasound, computed tomography and magnetic resonance imaging suggested only areas of focal fatty sparing but could not eliminate the concern for metastases. A (99m)technetium-labelled sulphur colloid scan, however, revealed areas of increased uptake consistent with multiple focal nodular hyperplasia. This diagnosis was ultimately confirmed with a liver biopsy. The investigation of a patient with a malignancy and expanding hepatic lesions is challenging. This case illustrates the usefulness of the (99m)technetium-labelled sulphur colloid scan in the evaluation of patients with hepatic lesions.

Adipose Tissue↗