Risk factors for anaemia in human immunodeficiency virus/hepatitis C virus-coinfected patients treated with interferon plus ribavirin.

The most frequent and the most troublesome adverse effect of interferon plus ribavirin-based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48-week trial comparing peginterferon (peg-IFN) alpha 2b plus ribavirin with interferon alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty-one (15.9%) of the 383 patients who received at least one dose of anti-HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64-6.54, P = 0.0008) and peg-IFN (OR, 2.35; 95% CI, 1.16-4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26-0.49, P < 0.0001) and in patients receiving protease inhibitor-based antiretroviral therapy (OR, 0.51 95% CI, 0.30-0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti-HCV therapy.

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.

[Surgical site infections after cesarean section: results of a five-year prospective surveillance]. / Infections de site opératoire chez les patientes césarisées: bilan de 5 années de surveillance.

AIMS: To determine the incidence of surgical site infections and to identify risk factors for infections. METHOD: A prospective study of surgical site infections (SSI) after cesarean section was carried out from September 1997 to September 1998 (pilot study) and from January 2000 to August 2003, using the methodology of the American National Nosocomial Infection Surveillance System. Follow up of women was performed by midwives until discharge and during the post-natal visit. Suspected surgical site infections were confirmed by surgeons and infection control practitioners. The microbiological file of each patient was edited 30 days after cesarean section. Risk factors were analyzed using a logistic regression model. RESULTS: During the pilot study, infection rate was estimated at 3.2%. At multivariate analysis, factors independently associated with an increased risk of SSI were ASA score > 1, performance of cesarean section in a room not dedicated to this activity, and use of an open urine drainage system. During the following years (2000-2003), infection rates progressively decreased to reach 1.9% in 2003. Infections included superficial wound infections (involving skin and subcutaneous tissue) (47%), deep wound infections (involving deep and soft tissue (fascia and muscle) (20%) and organ/space infections (i.e. endometritis, pelvic abscess) (33%). Infections occurred after patient discharge in 47.5% of cases and diagnosis was based only on clinical findings in 30% of cases. Infected patients were hospitalized longer (median: 6 days) than non infected patients. CONCLUSION: Prospective surveillance of SSI led to better awareness of infectious problems among health care workers, to identification of risk factors and evaluation of health procedures. Surveillance contributed to a decrease in nosocomial infections.

Long-term outcome and treatment modifications in a prospective cohort of human immunodeficiency virus type 1-infected patients on triple-drug antiretroviral regimens. Triest Cohort Investigators.

We designed a cohort in order to assess the long-term effects of triple-drug antiretroviral combinations in 608 patients infected with human immunodeficiency virus type 1 (HIV-1). We recruited patients who had been previously treated with nucleoside analogues as well as treatment-naive patients who were starting triple-drug antiretroviral combinations consisting of nucleoside analogues, either alone or in combination with a protease inhibitor. After a median follow-up time of 22 months, the incidence rates of acquired immune deficiency syndrome-defining events and death were, respectively, 6.9 (95% confidence interval [CI], 5.3-8.8) and 2.9 (95% CI, 1.9-4.2) per 100 person-years. Advanced clinical stage of disease (P=.004), a low CD4(+) cell count (P=.002), and a low quality-of-life score (P=.001) at baseline were independent predictors of clinical progression. The initial triple-drug combination was modified a total of 647 times in 321 patients. The only independent predictor of treatment modification was previous exposure to a nucleoside analogue in patients who did not receive a new nucleoside analogue at inclusion (P=.001). Plasma HIV RNA values below 500 copies/mL were obtained in 88% of the treatment-naive patients and in 57% of the previously treated patients (P<.001). Compared with previously treated patients who received > or = 1 new nucleoside analogue at enrollment, previously treated patients who did not receive a new nucleoside analogue at enrollment were twice as likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.8), and the antiretroviral-naive patients were significantly less likely to have plasma HIV RNA values >500 copies/mL at the last visit (adjusted OR, 0.2; 95% CI, 0.1-0.4).

Most probable number enumeration of H2-utilizing acetogenic bacteria from the digestive tract of animals and man.

A method is proposed that allows the enrichment and most probable number estimation of H2/CO2(-)utilizing acetogenic bacteria. It is based on the difference in acetate production for serial dilutions incubated under either a test H2/CO2 (4:1), or a control N2/CO2 (4:1) headspace atmosphere. A nutritionally non-selective medium was used, containing bromoethane-sulfonic acid as inhibitor of methanogenic archaea and 10% pre-incubated clarified rumen fluid. Acetogenic bacteria were enumerated in rumen and hindgut contents of animals and in human feces. They ranged from below 10(2) to above 10(8) per gram wet weight gut content and their population levels were the highest in the absence of methanogenesis. The method described therein should prove useful to better understand the diversity and ecological importance of dominant gut acetogens.

Pyxigraphic sampling to enumerate methanogens and anaerobes in the right colon of healthy humans.

BACKGROUND: A major limitation in studying the proximal human colonic flora is the lack of suitable sampling methods. The aim of this study was (1) to describe a prototype technique, pyxigraphy, which uses swallowed capsules containing a mechanism allowing the remote control of sampling the gastrointestinal tract contents, and (2) to use this sampling method to examine the distribution of methanogens in the colon of methane (CH4) excretors and non-CH4 excretors. METHODS: In six CH4 excretors and four non-CH4 excretors, samples of the right colonic contents were obtained by means of the pyxigraphic sampling method. Methanogens and total anaerobes were enumerated in both the right colonic and fecal contents. RESULTS: In CH4 excretors, the concentration of methanogens was higher in the feces than in the right colonic contents, representing 12% and 0.003%, respectively, of the total anacrobes (P < 0.02). In non-CH4 excretors, no difference was observed, methanogens representing < 0.003% of the total anaerobes in both the right colonic and fecal contents. CONCLUSIONS: Pyxigraphy is a noninvasive, simple, and safe sampling method that allows to study the microbial populations of the proximal colon. The results obtained showed that methanogens preferentially colonize the distal part of the colon in CH4 excretors.

Interrelations between populations of methanogenic archaea and sulfate-reducing bacteria in the human colon.

In humans, CH4 is produced in the colon by methanogenic archaea and is detected in breath samples from approximately 50% of healthy adults, identified as CH4-excretors. Methanogenesis and sulfate reduction have been described as two mutually exclusive processes, potentially regulated by sulfate availability. To determine whether microbial population balances reflected these apparently co-regulated activities, we compared sulfate-reducing bacteria, methanogenic archaea, sulfate and sulfide concentrations in faeces of 10 CH4-excretors (CH4+) and 9 non-CH4-excretors (CH4-). The mean +/- SE of the logarithm of methanogenic archaea per gram wet weight were 9.0 +/- 0.2 and 4.0 +/- 0.7 for CH4+ and CH4-, respectively (P < 0.001). Sulfate-reducing bacterial counts were 6.5 +/- 0.1 and 7.3 +/- 0.2, respectively (P < 0.001). Fecal sulfate and sulfide concentrations did not differ between groups. These results suggest that a competitive interrelation between methanogenic archaea and sulfate-reducing bacteria occurs in the human colon. However, it does not lead to a complete exclusion of the two populations.

Fecal recovery in humans of viable Bifidobacterium sp ingested in fermented milk.

Bifidobacterium sp is a natural component of the dominant colonic microflora that was recently introduced into several fermented dairy products. The aim of the present study was to study the fate of this microorganism in the human gut. On the basis of antibiotic resistance characters, a variant of Bifidobacterium sp that could be distinguished from indigenous bifidobacteria in the fecal flora was selected, and its survival and colonization in the colon was examined. This strain was used to ferment milk, and 125 g of the fermented product obtained was ingested by eight healthy volunteers three times daily for 8 days. Stools were recovered and weighed throughout the study. The results showed that the exogenous Bifidobacterium sp appeared in the stools and reached a mean level of 8.8 +/- 0.1 log colony-forming units per gram. This level was maintained as long as the fermented dairy product was consumed. When its ingestion stopped, the exogenous Bifidobacterium sp gradually decreased and was no longer detectable 8 days after cessation. The mean recovered quantity during the 8-day period of administration of the ingested bifidobacteria excreted in stools was 12.1 +/- 0.1 log colony-forming units per gram, i.e., 29.7% +/- 6% of the ingested bacteria, which was similar to the percentage that reached the colon in previous studies. It is concluded that under physiological conditions, exogenously administered Bifidobacterium sp do not colonize the human colon. However, the high fecal concentrations of exogenous bifidobacteria reached are compatible with metabolic "probiotic" activities.

[Survival of Lactobacillus acidophilus and Bifidobacterium sp. in the small intestine following ingestion in fermented milk. A rational basis for the use of probiotics in man]. / Survie, dans l'intestin grêle, de Lactobacillus acidophilus et Bifidobacterium sp, ingerés dans un lait fermenté. Une base rationnelle à l'utilisation de probiotiques chez l'homme.

Oro-ileal intubation was performed in 6 healthy volunteers who ingested, either 100 g of a fermented milk containing 10(8)/g Lactobacillus acidophilus and 10(7)/g Bifidobacterium sp or sterilized fermented milk along with a meal in random order. Lactobacillus acidophilus and Bifidobacterium were counted in the ileal fluid which was aspirated continuously for 8 h, and flow rates were calculated using the constant slow infusion of PEG 4000. After ingestion of fermented milk but not after control, hourly ileal flow rates of Lactobacillus acidophilus and Bifidobacterium increased form 4.8 +/- 0.2 and 4.9 +/- 0.6 to 7.2 +/- 0.3 and 8.0 +/- 0.3, respectively (mean +/- SE log10 CFU). 8.3 +/- 0.2 Lactobacillus acidophilus and 8.8 +/- 0.1 Bifidobacterium were recovered in the ileum which represented 1.5 percent and 37.5 percent of the ingested bacteria, respectively. In conclusion, under usual conditions of fermented milk ingestion, a large number of living Lactobacillus acidophilus and Bifidobacterium pass through the upper gastrointestinal tract and reach the colon.

Survival of bifidobacteria ingested via fermented milk during their passage through the human small intestine: an in vivo study using intestinal perfusion.

The ability of a strain of Bifidobacterium sp to survive passage through the upper gastrointestinal tract when ingested in fermented milk was investigated in six fasting healthy adults by using in vivo ileal perfusion. After ingestion of 10.0 +/- 0.5 log10 bifidobacteria in 400 g fermented milk, ileal flow of bifidobacteria increased significantly and reached a maximum of 8.8 +/- 0.2 log10 bifidobacteria/h 1.7 +/- 0.4 h after ingestion of fermented milk. The average number of bifidobacteria recovered from the terminal ileum during the 8 h after fermented-milk ingestion was 9.0 +/- 0.1 log10 and constituted 23.5 +/- 10.4% of the number ingested. These results indicate that in healthy adults Bifidobacterium sp survive transit through the gastrointestinal tract when ingested in fermented milk. Further studies are needed to investigate the behavior of these exogenous bacteria in the colonic lumen and to explore their effects on the physiology of the human gastrointestinal tract.

Segregation of HLA-DR2 among affected and non-affected offspring of 66 families with type 1 (insulin-dependent) diabetes.

Segregation of HLA-DR2 among affected and unaffected offspring was studied in 66 HLA-genotypes families with Type 1 diabetes in whom at least one parent carried DR2. The frequency of DR2-positive parents (21%) was not different from that of control families (29%). Among the diabetic probands, the gene frequency of DR2 was significantly decreased compared with control subjects (0.05 versus 0.17, p less than 0.001) as were DR5 (0.07 versus 0.17, p less than 0.01) and DR7 (0.06 versus 0.13, p less than 0.003). Twenty probands carried DR2, in 11 or whom (55%) it was found in combination with either DR3 or DR4. The nine cases who carried another DR allele included one who was DR2 homozygous. Transmission of DR2 was reduced in affected offspring, and random in unaffected siblings, compared with the expected ratio. However, when the DR2 transmission was analysed separately for parents bearing DR2 with DR3, DR4 or another DR allele, it appeared that DR2 transmission to affected offspring was random when the parents carried neither DR3 or DR4, the transmission deficit being due to over-transmission of DR3 and DR4. The haplotype analysis showed that the haplotype A3, Cw7, B7, GfS, DR2, found in 19% of "non-diabetic" DR2 haplotypes was practically absent among "diabetic" DR2-haplotypes (4%). In conclusion, population and segregation analysis could not demonstrate a specific protective effect of DR2.

Age--related heterogeneity of insulin-dependent diabetes mellitus.

One hundred and thirty-three insulin-dependent diabetic (IDD) patients were genotyped for HLA-A, B, C, DR and 123 of them for Bf. The study shows a relationship between these genes and the age of onset of diabetes and emphasizes the possible heterogeneity of the disease. When patients under the age of 0 years at the onset of the disease were compared with those aged 11 to 29 years, a significant excess of HLA-B18 (41% versus 15%, p less than 0.001) and BfF1 (40% versus 21%, P less than 0.05) was observed. The haplotype B18, BfF1 was also more frequent in the first group of patients (haplotype frequency 18% versus 6%, p less than 0.02). The frequency of the whole haplotype Cw5, B18, BfF1, DR3 and of its segment BfF1, DR3, and the strength of the gametic associations between these alleles were much higher in IDD patients than in non-diabetic controls, irrespective of the age of onset of their diabetes. The association between early age of onset of IDD and the B18, BfF1 haplotype independently of DR3 (no association between age and DR3) suggests that a factor influencing the onset of the disease in young children could be under the control of (1) gene (s) in linkage disequilibrium with B18 and/or BfF1.