The effects of local review on informed consent documents from a multicenter clinical trials consortium.

There is increasing controversy about the appropriate role of the local institutional review board in the review of multicenter clinical studies. We evaluated the effects of the local review process at 25 study sites on the consent forms from two studies of the Tuberculosis Trials Consortium, a multicenter trials group. Two independent reviewers classified all changes made in the centrally approved consent forms; a third reviewer evaluated those changes if the two initial reviewers disagreed.

The developmental expression of cell cycle regulators in Xenopus laevis.

Several cyclins and cdks have been cloned in Xenopus, but their developmental expression has not been thoroughly examined. We have analyzed the temporal and spatial expression of cdk1, cdk2, cdk4 and cyclins D1, D2, E, A1, A2 and B1 by in situ hybridization. The transcripts of these cyclins and cdks exhibit striking tissue-restricted expression patterns very early in development that cannot be strictly correlated with proliferation.

Low isoniazid concentrations and outcome of tuberculosis treatment with once-weekly isoniazid and rifapentine.

To understand why once-weekly isoniazid/rifapentine therapy for tuberculosis was less effective than twice-weekly isoniazid/rifampin, we studied human immunodeficiency virus-seronegative patients with either failure (n = 4), relapse (n = 35), or cure (n = 94), recruited from a comparative treatment trial. In multivariate analyses that were adjusted for severity of disease, low plasma concentrations of isoniazid were associated with failure/relapse with once-weekly isoniazid/rifapentine (median isoniazid area under the concentration-time curve for 12 hours after the dose [AUC(0-12)] was 36 microg x hour/ml in failure/relapse versus 56 microg x hour/ml in control cases p = 0.005), but not with twice-weekly isoniazid/rifampin.

The cdk inhibitor p27Xic1 is required for differentiation of primary neurones in Xenopus.

We have investigated the role of the cyclin-dependent kinase inhibitor, p27(Xic1), in the coordination of cell cycle exit and differentiation during early neurogenesis. We demonstrate that p27(Xic1) is highly expressed in cells destined to become primary neurones and is essential for an early stage of neurogenesis. Ablation of p27(Xic1) protein prevents differentiation of primary neurones, while overexpressing p27(Xic1) promotes their formation.

A single cdk inhibitor, p27Xic1, functions beyond cell cycle regulation to promote muscle differentiation in Xenopus.

The molecular basis of the antagonism between cellular proliferation and differentiation is poorly understood. We have investigated the role of the cyclin-dependent kinase inhibitor p27(Xic1) in the co-ordination of cell cycle exit and differentiation during early myogenesis in vivo using Xenopus embryos. In this report, we demonstrate that p27(Xic1) is highly expressed in the developing myotome, that ablation of p27(Xic1) protein prevents muscle differentiation and that p27(Xic1) synergizes with the transcription factor MyoD to promote muscle differentiation.

Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomised clinical trial.

Background: Rifapentine has a long half-life in serum, which suggests a possible treatment once a week for tuberculosis. We aimed to compare rifapentine and isoniazid once a week with rifampicin and isoniazid twice a week.

Methods: We did a randomised, multicentre, open-label trial in the USA and Canada of HIV-negative people with drug-susceptible pulmonary tuberculosis who had completed 2 months of a 6-month treatment regimen.

A prospective, randomized, double-blind study of the tolerability of rifapentine 600, 900, and 1,200 mg plus isoniazid in the continuation phase of tuberculosis treatment.

Once-weekly rifapentine 600 mg plus isoniazid (INH) during the continuation phase treatment of tuberculosis is associated with a relapse rate higher than that of twice-weekly rifampin plus INH. The safety and tolerability of higher rifapentine doses need to be determined. We conducted a prospective, randomized, double-blind trial of rifapentine at three doses (600, 900, and 1,200 mg) plus INH 15 mg/kg once weekly in the continuation phase treatment of culture-positive tuberculosis in 150 human immunodeficiency virus-seronegative adults.

Hes6 regulates myogenic differentiation.

Hes6 is a basic helix-loop-helix transcription factor homologous to Drosophila Enhancer of Split (EoS) proteins. It is known to promote neural differentiation and to bind to Hes1, a related protein that is part of the Notch signalling pathway, affecting Hes1-regulated transcription. We show that Hes6 is expressed in the murine embryonic myotome and is induced on C2C12 myoblast differentiation in vitro.

Effectiveness of once-weekly rifapentine and moxifloxacin regimens against Mycobacterium tuberculosis in mice.

Mice infected with 1.6 x 10(7) CFU of Mycobacterium tuberculosis were treated 14 days later for 6 months with a regimen of once-weekly 10 mg of rifapentine and 75 mg of isoniazid per kg of body weight supplemented with either 150 mg of streptomycin per kg or 100 mg of moxifloxacin per kg during either both the 2-week daily initial and once-weekly continuation phases or only in the daily 2-week initial phase. On completion of treatment, all lung cultures were negative, except for three mice, each with a single colony: two whose rifapentine-isoniazid regimen was supplemented with streptomycin during the whole course of therapy and one whose rifapentine-isoniazid regimen had no initial daily phase, but was supplemented with streptomycin and moxifloxacin during the whole course of therapy.

Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults.

Background: Treatment of latent infection is needed to protect HIV-infected individuals against tuberculosis. A previous report addressed short-term efficacy of three regimens in HIV-infected adults. We now report on long-term efficacy of the study regimens.

Surgical options for short bowel syndrome.

Most children with short bowel syndrome experience spontaneous small bowel adaptation over time. This allows the majority to be weaned from parenteral nutrition. There are, however, some children who cannot be weaned and are potential candidates for techniques to promote intestinal adaptation and intestinal lengthening.

Antituberculosis activity of once-weekly rifapentine-containing regimens in mice. Long-term effectiveness with 6- and 8-month treatment regimens.

The effectiveness of various once-weekly 10 mg/kg rifapentine (P)- containing regimens for treatment of tuberculosis was assessed in mice infected intravenously with 4.3 x 10(6) colony-forming units (cfu) of Mycobacterium tuberculosis H37Rv, and treated 14 d later with various combinations of rifampin (R), P, isoniazid (H), pyrazinamide (Z), ethambutol (E), or streptomycin (S). Control mice treated daily with either 2-mo HRZ + 4-mo HR or 2-mo HRZ + 6-mo HE were rendered spleen and lung culture-negative at 6 mo and 8 mo, respectively.

Tuberculosis prevention and control activities in the United States: an overview of the organization of tuberculosis services.

After a 20% increase in tuberculosis (TB) cases between 1986 and 1992, TB cases in the United States have declined from 1993 through 1997, an average of 5 to 7 per cent per year. In this paper, we review trends and the current epidemiology of TB in the US, present a brief history of TB control efforts in the country, and present the key strategies for TB control in the US. We describe the current organizational structure of TB services in the US, the role of the private sector in TB control, and how TB control is funded.

Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Tuberculosis Trials Consortium.

Background: Rifapentine is a cyclopentyl-substituted rifamycin whose serum half-life is five times that of rifampin. The US Public Health Service Study 22 compared a once-weekly regimen of isoniazid and rifapentine with twice weekly isoniazid and rifampin in the continuation phase (the last 4 months) of treatment for pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients. This report concerns only the HIV-seropositive part of the trial, which has ended.

Measles control in Kinshasa, Zaire improved with high coverage and use of medium titre Edmonston Zagreb vaccine at age 6 months.

Background: To improve measles control in Kinshasa, Zaire, a project to increase vaccine coverage was begun in 1988, and in 1989, the city vaccination programme changed measles vaccination policy from Schwartz vaccine at age 9 months to medium titre Edmonston Zagreb (EZ) vaccine at age 6 months. We report the impact of the programme on measles incidence and mortality.

Methods: Data on vaccine coverage were obtained from cluster sample surveys conducted every 1-2 years and from routine reports of vaccine doses administered.

Quality of sexually transmitted disease services in Jamaica: evaluation of a clinic-based approach. Collaborative Working Group on Indicators of STD Case Management.

As part of a larger strategy to develop global indicators of HIV (human immunodeficiency virus) infection prevention programmes, a clinic-based method for the assessment of sexually transmitted disease (STD) service quality was developed and field tested by trained observers who visited a random sample of public-sector clinics in Jamaica in October 1991. The assessment included an inventory of equipment and drugs, interviews with clinic staff, and observations of 27 health workers in 15 clinics as they provided services to 115 patients presenting for STD care. This observation-based method provided Jamaican programme managers with descriptive data on STD case management in public clinics within a one-month study period at an approximate local cost of US+ 5000.

The effect of US preexposure on conditioned taste aversion: lack of postconditioning recovery of the aversion.

Although the CS preexposure effect in CTA was once viewed exclusively as an acquisition failure, recent studies have suggested that the latent inhibition phenomenon is the result of retrieval impairment. This interpretive challenge is based on the unexpected finding that recovery of the aversion occurs over a long retention interval following conditioning (Kraemer, Lariviere, & Spear, Animal Learning and Behavior, 16, 185-190, 1988; Bakner, Strohen, Nordeen, & Riccio, Physiology & Behavior, 50, 1269-1272, 1991). This study examined whether a similar recovery occurs after US preexposure.

Changes in use of health services in a rural health zone in Zaire.

As part of the Combatting Childhood Communicable Diseases (CCCD) project funded by the US Agency for International Development (USAID), the Zairian CCCD programme conducted surveys in the rural health zones of Kingandu and Pai-Kongila, Zaire, in 1984-1985 and 1988-1989 to determine whether a strategy of selective primary health care would affect childhood mortality. This paper describes the changes in the medical care infrastructure and the increasing coverage of selected services. The strategies evaluated were vaccination, oral rehydration therapy, and treatment of febrile episodes with antimalarial drugs for children; and tetanus vaccination and malaria prophylaxis for pregnant women.

Pleural effusion resulting from metastatic papillary carcinoma of the thyroid.

We present a patient with a symptomatic pleural effusion resulting from papillary carcinoma of the thyroid metastatic to the pleura. Distinctive features include clinically evident pleural metastasis and the presence of psammoma bodies in the pleural fluid, which are characteristic (albeit not pathognomonic) of papillary carcinoma of the thyroid.

Split-mixed insulin regimen with human ultralente before supper and NPH (isophane) before breakfast in children and adolescents with IDDM.

Objective: Fasting hyperglycemia is common in patients with insulin-dependent diabetes mellitus (IDDM) treated with twice-daily subcutaneous insulin regimens. We postulated that substituting human ultralente insulin for the presupper dose of intermediate-acting insulin would improve overnight glycemic control in children and adolescents with IDDM.

Research Design And Methods: This 6-mo double-blind crossover study compared a conventional insulin regimen, a mixture of human NPH and regular given before both breakfast and supper (NPH), with a novel twice-daily regimen in which human ultralente replaced NPH before the evening meal (ultralente).

Acute gastrointestinal illness and child care arrangements.

This study uses data from the 1981 National Health Interview and the 1981 Child Health Supplement to assess the extent to which family day care homes and child care centers pose a risk of acute gastrointestinal illness among preschool children. The study uses a nationally representative sample of children 0-5 years of age (n = 4,845). Acute gastrointestinal illness was identified from parental reports of acute illness in a 2-week period.

A statistical analysis on the relationship of organism and site of infection to antimicrobial susceptibilities.

Disc agar diffusion tests were performed on 1340 clinical isolates (six common pathogens) to determine if the site of infection influenced antimicrobial susceptibility results for a given organism. There were several mathematically significant differences among sites and organisms, however the most important included cefoperazone (wound), piperacillin (sputum and urine) and tobramycin (sputum) against P. aeruginosa.