Biodegradability of Chlorophenols in Surface Waters from the Urban Area of Buenos Aires.

Biodegradability of 2-Chlorophenol (2-CP), 3-Chlorophenol (3-CP), 4-Chlorophenol (4-CP), 2,4-Dichlorophenol (2,4-DCP) and 2,4,6 Trichlorophenol (2,4,6-TCP) has been tested in surface waters in the urban area of Buenos Aires. Samples were taken from the La Plata River and from the Reconquista and Matanza-Riachuelo basins, with a total amount of 18 sampling points. Water quality was established measuring chemical oxygen demand (COD), biochemical oxygen demand (BOD5), and both Escherichia coli and Enterococcus counts. Biodegradability was carried out by a respirometric method, using a concentration of 20 mg L-1 of chlorophenol, and the surface water as inoculum. Chlorophenols concentration in the same water samples were simultaneously measured by a solid phase microextraction (SPME) procedure followed by gas chromatography-mass spectrometry (GC-MS). 2,4-DCP was the most degradable compound followed by 2,4,6-TCP, 4-CP, 3-CP and 2-CP. Biodegradability showed no correlation with compound concentration. At most sampling points the concentration was below the detection limit for all congeners. Biodegradability does not correlate even with COD, BOD5, or fecal contamination. Biodegradability assays highlighted information about bacterial exposure to contaminants that parameters routinely used for watercourse characterization do not reveal. For this reason, they might be a helpful tool to complete the characterization of a site.

Implication of NOTCH1 gene in susceptibility to anxiety and depression among sexual abuse victims.

Sexual abuse contributes to the development of multiple forms of psychopathology, including anxiety and depression, but the extent to which genetics contributes to these disorders among sexual abuse victims remains unclear. In this translational study, we first examined gene expression in the brains of rodents exposed to different early-life conditions (long, brief or no maternal separation). Hypothesizing that genes revealing changes in expression may have relevance for psychiatric symptoms later in life, we examined possible association of those genes with symptoms of anxiety and depression in a human sample of sexual abuse victims. Changes in rodent brain gene expression were evaluated by means of correspondence and significance analyses of microarrays by comparing brains of rodents exposed to different early-life conditions. Tag single-nucleotide polymorphisms (SNPs) of resulting candidate genes were genotyped and tested for their association with symptoms of anxiety and depression (Hospital Anxiety and Depression Scale) in a sample of 361 sexual abuse victims, using multinomial logistic regression. False discovery rate was applied to account for multiple testing in the genetic association study, with q-value of 0.05 accepted as significant. We identified four genes showing differential expression among animals subjected to different early-life conditions as well as having potential relevance to neural development or disorders: Notch1, Gabrr1, Plk5 and Zfp644. In the human sample, significant associations were observed for two NOTCH1 tag SNPs: rs11145770 (OR=2.21, q=0.043) and rs3013302 (OR=2.15, q=0.043). Our overall findings provide preliminary evidence that NOTCH1 may be implicated in the susceptibility to anxiety and depression among sexual abuse victims. The study also underscores the potential importance of animal models for future studies on the health consequences of early-life stress and the mechanisms underlying increased risk for psychiatric disorders.

Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort.

BACKGROUND: Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). AIMS: To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. METHODS: Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. RESULTS: Only 54% (n=312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the nine participating centres (27% to 70%, P≤0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (48% vs. 69%, P≤0.0001). Independent predictors of colonoscopic surveillance were male gender, UC IBD subtype, longer disease duration, previous history of CRC and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 71%, 27 and 30% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. CONCLUSIONS: Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis.

Association between entero-hepatic Helicobacter species and Crohn's disease: a prospective cross-sectional study.

BACKGROUND: The pathogenesis of Crohn's disease (CD) involved microbial factors. Some Helicobacter species, the so-called entero-hepatic Helicobacters (EHH), can naturally colonize the intestinal surface and have been detected in humans. Aim To look for an association between CD and the presence of EHH DNA in intestinal biopsies. METHODS: Two groups of patients were included prospectively in a multicentre cross-sectional study: CD patients with an endoscopic post-operative recurrence within 2 years following a surgical resection and controls screened for colorectal polyps or cancer. Intestinal biopsies were taken for Helicobacter culture and Helicobacter 16S DNA detection. If positive, the EHH species were identified with specific PCRs, sequencing and denaturing gradient gel electrophoresis. RESULTS: In the 165 included patients (73 CD and 92 controls), Helicobacter cultures were negative. PCR was positive in 44% of CD and 47% of controls. After age-adjustment, CD was significantly associated with EHH in intestinal biopsies (OR = 2.58; 95%CI: 1.04-6.67). All EHH species detected were identified as Helicobacter pullorum and the closely related species Helicobacter canadensis. CONCLUSION: Crohn's disease is associated with the presence of EHH species DNA in intestinal biopsies after adjustment for age. Whether these species play a role in the pathophysiology of CD remains to be determined.

The prevalence of significant left-right hip bone mineral density differences among black and white women.

SUMMARY: In a cross-sectional retrospective study, we examined the prevalence of significant opposite hip bone mineral density difference among white and black women. Left-right hip bone mineral density difference was a common finding in both races, raising the possibility that osteoporosis can be missed if only one hip is imaged. INTRODUCTION: We examined the prevalence of significant left-right hip bone mineral density (BMD) difference among black and white female subjects and its implications on the diagnosis of osteoporosis. METHODS: This was a retrospective review of dual energy X-ray absorptiometry (DXA) data in black and white subjects age 50 years and older. One thousand four hundred seventy-seven scans obtained using a GE Lunar Prodigy scanner in dual hip mode were analyzed (24% black, 76% white). Significant left-right hip BMD difference was considered present when the subregion least significant change (LSC) was exceeded. Its prevalence was determined, along with consequences on the diagnosis of osteoporosis. RESULTS: Significant differences in BMD were common in both races; the LSC was exceeded in 47% of the patients at the total hip, 37% at the femoral neck, and 53% at the trochanter. Diagnostic agreement was lower when the LSC was exceeded than when it was not. The LSC was exceeded in a statistically significant number of black and white patients with normal or osteopenic spines and unilateral hip osteoporosis. CONCLUSIONS: Significant left-right hip BMD difference is a common finding among black and white women and can result in osteoporosis being missed if only one hip is imaged.

Infliximab treatment for symptomatic Crohn's disease strictures.

BACKGROUND: Some reports have suggested that infliximab may induce obstructive symptoms and, although there is no firm evidence, it is usually contra-indicated in-patients with Crohn's disease (CD) and strictures. AIMS: To evaluate the effect of infliximab on symptomatic strictures of the small intestine in CD and to identify predictive factors of clinical response. METHODS: This retrospective study included symptomatic patients treated with infliximab after conventional treatment had failed. The short-term (week 8) and long-term results were classified according to predefined criteria as complete, partial response, or failure. RESULTS: Before infliximab, 18 patients had complete obstruction or intermittent chronic abdominal pain. Fourteen patients were treated by corticosteroids and 13 received immunosuppressive drugs. At week 8, complete, partial response and failure were observed in 10, 7 and 1 patients, respectively. Fourteen patients continued maintenance infliximab treatment after week 8. During the most recent evaluation (median follow-up: 18 months), 8 patients were on maintenance infliximab treatment; only eight were still on prednisone; there were five complete responses, 10 partial responses and three failures. Initiating prednisone or increasing its dosage was the only factor associated with a short-term complete response. CONCLUSIONS: Infliximab may be effective in patients with symptomatic strictures from CD, and should be tested before considering surgery.

Clinical outcomes of renal transplant recipients treated with enteric-coated mycophenolic acid vs. mycophenolate mofetil as a switch agent using a primary steroid-free rapamune and microemulsion cyclosporine protocol.

Since 2002 our transplant program has utilized a steroid free, cyclosporine (CSA)- and rapamycin (RAPA)-based maintenance immunosuppression regimen. In cases where it has been desirable to avoid the potential nephrotoxicity with this regimen we have used mycophenolic acid (MPA) as our "switch" drug of choice. Both mycophenolate mofetil (MMF) (Roche Inc., Nutley, NJ, USA) and enteric-coated MPA (ECM) (Novartis, East Hanover, NJ, USA) have been used. In this study, we retrospectively compared the tolerability of the two formulations of MPA. Thus we compared 103 recipients switched to RAPA/MMF (RMM group) to 114 switched to RAPA/ECM (REC group). There was a significantly higher incidence of patients requiring dose changes and drug discontinuation in the RMM group, as well as an increased frequency of dose changes. There were significantly more acute rejection episodes and kidney losses in the dose adjustment vs. no dose adjustment patients. However, when comparing the incidence of acute rejection and kidney loss between the RMM and REC groups, there was no significant difference. We conclude that in this cohort of recipients, the ECM formulation of MPA was better tolerated than the MMF formulation, resulting in fewer patients requiring dose adjustments or drug discontinuation.

Cytomegalovirus accelerates chronic allograft nephropathy in a rat renal transplant model with associated provocative chemokine profiles.

BACKGROUND: Studies have shown that rat cytomegalovirus (RCMV) infection accelerates transplant vascular sclerosis (TVS) in rat heart and small bowel allotransplants. In these models, RCMV-accelerated TVS results from increased graft infiltration of inflammatory cells through up-regulation of chemokine expression. The aim of this study was to determine if RCMV infection accelerates renal transplant chronic allograft nephropathy (CAN), and the role of chemokines in this process. METHODS: F344 kidneys were transplanted into Lewis recipients with and without RCMV infection. To monitor CAN, serum creatinine (Cr) levels were measured starting at 4 weeks posttransplantation. At 7 and 21 days, and at terminal rejection, grafts were examined for histologic changes, inflammatory cell infiltrates, viral load, and chemokine expression profiles. RESULTS: By week 8, serum Cr showed significant elevation (P < .01) in the RCMV-infected group vs uninfected group, and remained significantly elevated through the end of the study. RCMV+ renal allografts had significant inflammatory cell infiltration and increased CAN at postoperative day (POD) 28. The CC chemokines RANTES, MCP-1, and MIP-1alpha, and the CXC chemokine IP-10 were up-regulated in RCMV-infected vs uninfected allografts. IP-10 was significantly up-regulated early in the process, whereas RANTES and MCP-1 were induced at a later time. CONCLUSIONS: RCMV infection accelerates CAN, with associated graft inflammatory infiltrates, which is paralleled by an increase in expression of CC and CXC chemokines. Our findings suggest that the early induction of IP-10 in the infected allografts promotes alterations in T-cell and monocyte migration to the graft, which initiates accelerated inflammatory and fibrotic changes associated with CAN.

Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain.

Interest in BDNF (brain-derived neurotrophic factor) as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF and its receptor tyrosine kinase TrkB (tropomyosin receptor kinase B) to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and synaptic plasticity in the adult brain. Development of stable LTP (long-term potentiation) in response to high-frequency stimulation requires new gene expression and protein synthesis, a process referred to as synaptic consolidation. Several lines of evidence have implicated endogenous BDNF-TrkB signalling in synaptic consolidation. This mini-review emphasizes new insights into the molecular mechanisms underlying this process. The immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is strongly induced and transported to dendritic processes after LTP induction in the dentate gyrus in live rats. Recent work suggests that sustained synthesis of Arc during a surprisingly protracted time-window is required for hyperphosphorylation of actin-depolymerizing factor/cofilin and local expansion of the actin cytoskeleton in vivo. Moreover, this process of Arc-dependent synaptic consolidation is activated in response to brief infusion of BDNF. Microarray expression profiling has also revealed a panel of BDNF-regulated genes that may co-operate with Arc during LTP maintenance. In addition to regulating gene expression, BDNF signalling modulates the fine localization and biochemical activation of the translation machinery. By modulating the spatial and temporal translation of newly induced (Arc) and constitutively expressed mRNA in neuronal dendrites, BDNF may effectively control the window of synaptic consolidation. These findings have implications for mechanisms of memory storage and mood control.

Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo controlled GETAID trial.

BACKGROUND AND AIMS: Early endoscopic recurrence is frequent after intestinal resection for Crohn's disease. Bacteria are involved, and probiotics may modulate immune responses to the intestinal flora. Here we tested the probiotic strain Lactobacillus johnsonii LA1 in this setting. PATIENTS AND METHODS: This was a randomised, double blind, placebo controlled study. Patients were eligible if they had undergone surgical resection of <1 m, removing all macroscopic lesions within the past 21 days. Patients were randomised to receive two packets per day of lyophilised LA1 (2 x 10(9) cfu) or placebo for six months; no other treatment was allowed. The primary endpoint was endoscopic recurrence at six months, with grade >1 in Rutgeerts' classification or an adapted classification for colonic lesions. Endoscopic score was the maximal grade of ileal and colonic lesions. Analyses were performed primarily on an intent to treat basis. RESULTS: Ninety eight patients were enrolled (48 in the LA1 group). At six months, endoscopic recurrence was observed in 30/47 patients (64%) in the placebo group and in 21/43 (49%) in the LA1 group (p = 0.15). Per protocol analysis confirmed this result. Endoscopic score distribution did not differ significantly between the LA1 and placebo groups. There were four clinical recurrences in the LA1 group and three in the placebo group. CONCLUSION: L johnsonii LA1 (4 x 10(9) cfu/day) did not have a sufficient effect, if any, to prevent endoscopic recurrence of Crohn's disease.

Osteoporosis in inflammatory bowel disease: effect of calcium and vitamin D with or without fluoride.

BACKGROUND: Previous data have indicated low bone formation as a mechanism of osteoporosis in inflammatory bowel disease. Fluoride can stimulate bone formation. AIM: To assess the effect of fluoride supplementation on lumbar spine bone mineral density in osteoporotic patients with inflammatory bowel disease treated in parallel with calcium and vitamin D. METHODS: In this prospective, randomized, double-blind, parallel and placebo-controlled study, 94 patients with inflammatory bowel disease (lumbar spine T score below - 2 standard deviations, normal serum 25OH vitamin D), with a median age of 35 years, were included. Bone mineral density was measured by dual-energy X-ray absorptiometry. Patients were randomized to receive daily either sodium monofluorophosphate (150 mg, n=45) or placebo (n=49) for 1 year, and all received calcium (1 g) and vitamin D (800 IU). The relative change in bone mineral density from 0 to 12 months was tested in each group (fluoride or placebo) and compared between the groups. RESULTS: Lumbar spine bone mineral density increased significantly in both groups after 1 year: 4.8 +/- 5.6% (n=29) and 3.2 +/- 3.8% (n=31) in the calcium-vitamin D-fluoride and calcium-vitamin D-placebo groups, respectively (P < 0.001 for each group). There was no difference between the groups (P=0.403). Similar results were observed according to corticosteroid intake or disease activity. CONCLUSIONS: Calcium and vitamin D seem to increase lumbar spine density in osteoporotic patients with inflammatory bowel disease; fluoride does not provide further benefit.

A barley gene family homologous to the maize rust resistance gene Rp1-D.

Many characterized plant disease resistance genes encode proteins which have conserved motifs such as the nucleotide binding site. Conservation extends across different species, therefore resistance genes from one species can be used to isolate homologous regions from another by employing DNA sequences encoding conserved protein motifs as probes. Here we report the isolation and characterization of a barley ( Hordeum vulgare L.) resistance gene analog family consisting of nine members homologous to the maize rust resistance gene Rp1-D. Five barley Rp1-D homologues are clustered within approximately 400 kb on chromosome 1(7H), near, but not co-segregating with, the barley stem rust resistance gene Rpg1; while others are localized on chromosomes 3(3H), 5(1H), 6(6H) and 7(5H). Analyses of predicted amino-acid sequences of the barley Rp1-D homologues and comparison with known plant disease resistance genes are presented.

Can laparoscopy reduce hospital stay in the treatment of Crohn's disease?

PURPOSE: The aim of this article was to investigate the safety, outcome, length of stay, and cost of hospital admission in patients with Crohn's disease who underwent laparoscopy compared with open surgery. METHODS: Among 51 consecutive patients with inflammatory bowel disease (1996-2000), 46 with Crohn's disease were included in this nonrandomized prospective study. Of these, 20 patients underwent laparoscopic surgery and 26 underwent open surgery. Data collected included the following information: age, gender, body mass index, diagnosis, duration of disease, preoperative medical treatment, previous abdominal surgery, present indication for surgery, and procedure performed (comparability measures), as well as conversion to open surgery, operating time, time to resolution of ileus, morbidity, duration of hospital stay, and cost of hospital admission (outcome measures). RESULTS: There was no significant difference with respect to comparability measures between the laparoscopic and the open-surgery groups. There was no mortality. There was no intraoperative complication in either group and no conversion in the laparoscopic group. Operating time was significantly longer in the laparoscopic group (302 minutes) vs. the open group (244.7 minutes) (P < 0.05), but this difference disappeared when data were adjusted for the extra time required to perform the laparoscopic hand-sewn anastomoses (288.2 minutes vs. 244.7 minutes). Bowel function returned more quickly in the laparoscopic group vs. the open group in terms of passage of flatus (3.7 vs. 4.7 days) (P < 0.05) and resumption of oral intake (4.2 vs. 6.3 day) (P < 0.01). There were significantly fewer postoperative complications in the laparoscopic group (9.5 percent) vs. the open group (18.5 percent) (P < 0.05); the length of stay was significantly shorter in the laparoscopic group (8.3 days) vs. the open group (13.2 days) (P < 0.01); and the cost of hospital admission was significantly lower in the laparoscopic group ($6106, United States dollars) vs. the open group ($9829, United States dollars) (P < 0.05). CONCLUSION: There is a reduction in the postoperative ileus, length of stay, cost of hospital admission, and postoperative complication rate in the laparoscopic group. Laparoscopic surgery for Crohn's disease is safe, and it is potentially more cost-effective than traditional open surgery.

[Clinical and biological syndrome of intestinal malabsorption: diagnostic tests]. / Syndrome clinique et biologique de malabsorption intestinale: explorations fonctionnelles.

Malabsorption has miscellaneous clinical and biological presentations. They may vary according to the site of the absorption abnormality (luminal, parietal, vascular transport), its type and severity. The problem of the physician is to become alerted to the possibility of malabsorption in patients who present with signs and symptoms which may be the concern of almost any specialist beside gastroenterologists. Patient history, type of signs and symptoms, physical examination and simple biochemical and haematological parameters may be of major interest in this regard and will help in the choice of the functional tests to perform. They will confirm the presumed malabsorption, precise its type and severity and may guide towards its aetiology, the precise diagnosis of which will usually require other investigations.

A physical map of the syringomycin and syringopeptin gene clusters localized to an approximately 145-kb DNA region of Pseudomonas syringae pv. syringae strain B301D.

Genetic and phenotypic mapping of an approximately 145-kb DraI fragment of Pseudomonas syringae pv. syringae strain B301D determined that the syringomycin (syr) and syringopeptin (syp) gene clusters are localized to this fragment. The syr and syp gene clusters encompass approximately 55 kb and approximately 80 kb, respectively. Both phytotoxins are synthesized by a thiotemplate mechanism of biosynthesis, requiring large multienzymatic proteins called peptide synthetases. Genes encoding peptide synthetases were identified within the syr and syp gene clusters, accounting for 90% of the DraI fragment. In addition, genes encoding regulatory and secretion proteins were localized to the DraI fragment. In particular, the salA gene, encoding a regulatory element responsible for syringomycin production and lesion formation in P. syringae pv. syringae strain B728a, was localized to the syr gene cluster. A putative ATP-binding cassette (ABC) transporter homolog was determined to be physically located in the syp gene cluster, but phenotypically affects production of both phytotoxins. Preliminary size estimates of the syr and syp gene clusters indicate that they represent two of the largest nonribosomal peptide synthetase gene clusters. Together, the syr and syp gene clusters encompass approximately 135 kb of DNA and may represent a genomic island in P. syringae pv. syringae that contributes to virulence in plant hosts.

Hepatocellular carcinoma in patients with acute hepatic porphyria: frequency of occurrence and related factors.

BACKGROUND/AIMS: Previous retrospective studies have suggested an association between hepatocellular carcinoma and acute hepatic porphyrias. The incidence, the relative risk, the characteristics and the outcome of primary liver cancer were prospectively evaluated in patients with acute hepatic porphyrias; the molecular mechanism of carcinogenesis in these patients was also pointed out. METHODS: A cohort of 650 patients with acute hepatic porphyria was followed over 7 years. Standardized rate ratio was used to measure the relative risk of primary liver cancer after indirect standardization. Morphological and clinical aspects of primary liver cancer were investigated, and survival rates were calculated using the Kaplan-Meier method. Common etiological factors involved in liver carcinogenesis were screened. Excretion rates of porphyrin precursors, serum melatonin levels and mutations in the genes encoding for heme biosynthetic enzymes were studied. RESULTS: Hepatocellular carcinoma was found in four symptomatic and three asymptomatic patients (four female, three male). The overall standardized rate ratio was 36 (95% CI: 14-74). The 5-year disease-free survival was 43% in patients with hepatocellular carcinoma. Usual risk factors for primary liver cancer were not confounding factors. Hepatocellular carcinoma was not related to specific heme biosynthesis gene mutations. Heme precursors were significantly increased in porphyric patients with hepatocellular carcinoma, and serum melatonin levels were low. CONCLUSIONS: Acute hepatic porphyrias are risk factors for hepatocellular carcinoma. Hepatic porphyrias should be sought in patients with hepatocellular cancer without obvious etiology, and a periodic screening for hepatocellular carcinoma should be evaluated in these patients. Genes encoding for heme biosynthetic pathway may not act as tumor suppressor genes. Chronic increased levels of delta aminolevulinic acid could lead to the generation of free radicals and subsequently to hepatic carcinogenesis.

Genotypic analysis of thiopurine S-methyltransferase in patients with Crohn's disease and severe myelosuppression during azathioprine therapy.

BACKGROUND & AIMS: Myelosuppression in patients with Crohn's disease (CD) treated with azathioprine has been attributed to low activity of thiopurine S-methyltransferase (TPMT). Allelic variants of the TPMT gene responsible for changes in the enzyme activity have been characterized. We investigated the distribution of mutant alleles associated with TPMT deficiency in patients with CD and myelosuppression during azathioprine/6-mercaptopurine therapy. METHODS: Forty-one patients with CD were included. They developed leukopenia or thrombocytopenia during azathioprine or 6-mercaptopurine treatment. Polymerase chain reaction-based methods were used to search for mutations associated with TPMT deficiency. RESULTS: Four patients (10%) had 2 mutant alleles associated with TPMT deficiency, 7 (17%) had 1 mutant allele, and 30 (73%) had no known TPMT mutation. The delay between administration of the drug and occurrence of bone marrow toxicity was less than 1.5 months in the 4 patients with 2 mutant alleles, and ranged from 1 to 18 months in patients with 1 mutant allele and from 0.5 to 87 months in patients with normal genotype. CONCLUSIONS: Twenty-seven percent of patients with CD and myelosuppression during azathioprine therapy had mutant alleles of the TPMT gene associated with enzyme deficiency. Myelosuppression is more often caused by other factors. Continued monitoring of blood cell counts remains mandatory in patients treated with azathioprine.

Amantadine for chronic hepatitis C: pilot study in 14 patients.

BACKGROUND: Amantadine, a widely available antiviral drug, has been previously reported to be effective in patients with chronic hepatitis C who failed to respond to interferon-alpha therapy. Nevertheless, its efficacy has not been fully studied, particularly in naive patients. OBJECTIVE AND DESIGN: We conducted a pilot study to determine the efficacy and the safety of amantadine as initial therapy in patients with chronic hepatitis C. METHODS AND PARTICIPANTS: Fourteen consecutive patients (mean age, 40 years; M/F ratio, 9/5) with chronic hepatitis C, elevated alanine aminotransferase (ALT) and without cirrhosis were treated with a 6-month course of amantadine, 100 mg orally twice daily. Main outcome measures were ALT concentrations and serum hepatitis C virus-RNA (HCV-RNA) levels at the end of therapy. RESULTS: All adverse events were mild or moderate and were not treatment limiting. At the end of treatment, all patients had detectable serum HCV-RNA and only one patient had a normal ALT level. The serum HCV-RNA median level and the ALT median level were not significantly different at the end of treatment as compared to baseline levels. CONCLUSIONS: Our results show that amantadine alone cannot be recommended as an alternative therapy in patients with chronic hepatitis C.