Human immunodeficiency virus infection in urban Rwanda. Demographic and behavioral correlates in a representative sample of childbearing women

OBJECTIVE.--To determine behavioral and demographic risk factors for human immunodeficiency virus (HIV) infection in central Africa. DESIGN.--Cross-sectional survey. SETTING.--Kigali, Rwanda. PARTICIPANTS.--A representative sample of 1458 childbearing women aged 19 to 37 years who were recruited from outpatient prenatal and pediatric clinics at the only community hospital in the city. MAIN OUTCOME MEASURE.--Antibodies to HIV assessed by enzyme immunoassay and confirmed by Western blot or indirect immunofluorescence. RESULTS.--The HIV seroprevalence was 32% overall. Infection rates were higher in women who were single, in those in steady relationships that began after 1981, and in the 33% of women reporting more than one lifetime sexual partner. Women in legal marriages or monogamous partnerships had lower rates of infection, but even low-risk women had prevalences on the order of 20%. History of venereal disease in the past 5 years, although the strongest risk factor in a multiple logistic analysis (odds ratio, 2.7; 95% confidence interval, 2.0 to 3.7), was reported by only 30% of those infected. Having a male sexual partner who drank alcohol or who had higher income were significant risk factors for HIV infection in the multivariate analysis, but use of oral contraceptives and having an uncircumcised partner were not. CONCLUSIONS.--The epidemic of the acquired immunodeficiency syndrome in Rwanda has spread beyond high-risk groups to the general population of women without known risk factors. For most of these women, a steady male partner is the source of their HIV risk and therefore a vital target for intervention efforts.     

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP- sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.      

Structural studies on tazobactam.

Tazobactam (3, C10H12N4O5S) is an effective inhibitor of bacterial beta-lactamases. It crystallizes with unit cell dimensions a = 10.230 (2) A, b = 14.396 (2) A, and c = 17.291 (2) A in space group P2(1)2(1)2(1). Compared to the related inhibitor sulbactam (2), which lacks the triazole ring, crystalline tazobactam exhibits very similar beta-lactam geometry and the same S(1) envelope conformation of the thiazolidine ring. However, in both independent molecules of 3 a triazole ring nitrogen atom accepts an intermolecular hydrogen bond; similar interaction by this moiety of 3 with a hydrogen-bond donor on the enzyme, which is impossible for 2, could account for its enhanced inhibitory power. Semiempirical molecular orbital calculations show pronounced negative potential there. Molecular mechanics supports the hypothesis that the carboxyl group can rotate freely and the triazole ring can "flip".     

Frequency of colonization and pneumonia and development of resistance in long-term ventilated intensive-care patients subjected to selective decontamination of the digestive tract

Colonization of the oropharynx with potentially pathogenic microorganisms (PPM) is a highly significant factor in the pathogenesis of bacterial pneumonia in intensive care patients. Via colonization of the oropharynx, bacteria pass into the tracheobronchial tree, where they can give rise to pneumonia after overcoming pulmonary resistance mechanisms. By a new, prophylactic antibiotic treatment schedule consisting in selective decontamination of the digestive tract (SDD) with locally applied nonabsorbable antibiotics, Stoutenbeek achieved drastic lowering of the colonization and infection rate in trauma patients. In the present study, we wanted to check whether this new prophylactic antibiotic schedule can be applied on a surgical intensive care ward in all patients with long-term ventilation, irrespective of the diagnosis, and whether it affords advantages over a conventional antibiotic schedule. MATERIALS AND METHODS. All patients on a surgical intensive care ward in whom it was expected that mechanical ventilation would be necessary for more than 4 days were included in the study. During the first 6 months 83 patients were investigated, in whom antibiotics were only administered when the presence of infection had been confirmed, in accordance with generally accepted guidelines (control group). In the second 6-month period, 82 patients were selectively decontaminated with 4 x 100 mg polymyxin E, 4 x 80 mg tobramycin and 4 x 500 mg amphotericin B, administered through the gastric tube and in an antimicrobial paste in the oropharynx (SDD group). The SDD schedule entailed systemic administration of cefotaxime in the first 3-4 days. RESULTS. In the control group, enterobacteria/Pseudomonas spp. were isolated significantly more frequently than in the SDD group (P less than 0.001): in the pharyngeal smear in up to 53%, in the tracheal secretion up to 36%, and in the rectal smear in up to 93% of the patients In the SDD group in the 1 week the frequency of gram-negative aerobic bacteria in the pharynx decreased from 33% to 5%, in the tracheal secretion from 23% to 14% and in the rectum from 86% to 52% (24% in the second week). However, the decrease in gram-negative microorganisms was accompanied by significant increase in the frequency of Staphylococcus epidermidis and enterococci. The SDD schedule proved to be effective with regard to the rate of infection. In the control group, 35 patients developed pneumonia (42%) as against 5 patients receiving SDD prophylaxis (6%). The duration of mechanical ventilation in the patients with pneumonia was 5 days longer than in patients without pneumonia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.     

Novel Method for Processing Respiratory Specimens for Detection of Mycobacteria by Using C18-Carboxypropylbetaine: Blinded Study

A novel method for processing respiratory specimens to improve culture and acid-fast staining of mycobacteria is introduced. This new method utilized N,N-dimethyl-N-(n-octadecyl)-N-(3-carboxypropyl)ammonium inner salt (Chemical Abstract Service no. 78195-27-4), also known as C₁₈-carboxypropylbetaine (CB-18). In a blinded, five-center study, CB-18-based processing was compared to the standard method combining NALC and NaOH (NALC/NaOH). A total of 573 respiratory specimens were tested. Individual specimens were split approximately equally; the host institutions processed half of each specimen by the NALC/NaOH method, while the other half was processed with CB-18 at Quest Diagnostics—Baltimore. A total of 106 specimens were culture positive for acid-fast bacilli (AFB). Replacement of the primary decontamination agent with CB-18 caused changes in all diagnostic parameters. Aggregate culture sensitivity improved by approximately 43% (P < 0.01), and smear sensitivity improved by approximately 58% (P < 0.01). The sensitivity of smear relative to that of M. tuberculosis isolates exceeded 93% (P < 0.01) when specimens were processed with CB-18. The average times to a positive result were reduced by 7.3 days in liquid culture (P < 0.01) and 5.3 days on solid media (P < 0.05); however, the CB-18 method had a 20.8% contamination rate in liquid culture versus a rate of approximately 7.5% with NALC/NaOH processing. There were also unusual reductions in liquid culture sensitivity and smear specificity among CB-18-processed specimens. The characteristics of the latter parameters suggested that refinement of the CB-18 processing method should allow further improvements in culture sensitivity. This study showed that the CB-18 method has the potential to improve both smear and culture detection for these important human pathogens.     

A meta-analysis of experimental studies of diversion programs for juvenile offenders

Objective

Research to establish an evidence-base for the treatment of conduct problems and delinquency in adolescence is well established; however, an evidence-base for interventions with offenders who are diverted from the juvenile justice system has yet to be synthesized. The purpose of this study was to conduct a meta-analysis of experimental studies testing juvenile diversion programs and to examine the moderating effect of program type and implementation quality.

Method

A literature search using PsycINFO, Web of Science, and the National Criminal Justice Reference Service data-bases and research institute websites yielded 28 eligible studies involving 57 experimental comparisons and 19,301 youths.

Results

Recidivism was the most common outcome reported across all studies. Overall, the effect of diversion programs on recidivism was non-significant (k = 45, OR = 0.83, 95%CI = 0.43-1.58). Of the five program types identified, including case management (k = 18, OR = 0.78), individual treatment (k = 11, OR = 0.83), family treatment (k = 4, OR = 0.57), youth court (k = 6, OR = 0.93), and restorative justice (k = 6, OR = 0.87), only family treatment led to a statistically significant reduction in recidivism. Restorative justice studies that were implemented with active involvement of researchers led to statistically significant reductions in recidivism (k = 3, OR = 0.69). Other outcomes, including frequency of offending, truancy, and psycho-social problems were reported infrequently and were not subjected to meta-analysis.

Conclusions

High levels of heterogeneity characterize diversion research. Results of this study recommend against implementation of programs limited to case management and highlight the promise of family interventions and restorative justice.     

Stool microflora in extremely low birthweight infants

AIM: To serially characterise aerobic and anaerobic stool microflora in extremely low birthweight infants and to correlate colonisation patterns with clinical risk factors. METHODS: Stool specimens from 29 infants of birthweight <1000 g were collected on days 10, 20, and 30 after birth. Quantitative aerobic and anaerobic cultures were performed. RESULTS: By day 30, predominant species were Enterococcus faecalis, Escherichia coli, Staphylococcus epidermidis, Enterbacter cloacae, Klebsiella pneumoniae, and Staphylococcus haemolyticus. Lactobacillus and Bifidobacteria spp were identified in only one infant. In breast milk fed (but not in formula fed) infants, the total number of bacterial species/stool specimen increased significantly with time (2.50 (SE 0.34) on day 10; 3.13 (0.38) on day 20; 4.27 (0.45) on day 30) as did quantitative bacterial counts; Gram negative species accounted for most of the increase. On day 30, significant inverse correlations were found between days of previous antibiotic treatment and number of bacterial species (r=0.491) and total organisms/g of stool (r=0.482). Gestational age, birthweight, maternal antibiotic or steroid treatment, prolonged rupture of the membranes, and mode of delivery did not seem to affect colonisation patterns. CONCLUSIONS: The gut of extremely low birthweight infants is colonised by a paucity of bacterial species. Breast milking and reduction of antibiotic exposure are critical to increasing fecal microbial diversity.