Comparison of the induction of a 4S beta-naphthoflavone-binding protein, cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase in beta-naphthoflavone-treated rats

A profound induction of a 4S beta-naphthoflavone (BNF)-binding protein, cytochrome P450 1A1 (CYP1A1) and NAD(P)H:quinone oxidoreductase (NQO1) activities was determined in the livers of Sprague-Dawley rats following intraperitoneal administration of BNF. Time-course of this induction differed for CYP1A1 and NQO1 activities, suggesting independent regulation of the phase I and II enzymes of xenobiotic metabolism. Time-course of the induction of CYP1A1 and BNF-binding activities was similar, suggesting that regulation of a 4S BNF- binding protein is associated with that of the CYP1A1 enzyme activity. The BNF specific binding to a 4S protein was inhibited by exogenous (BNF) and endogenous (indirubin and indigo) ligands for the aryl hydrocarbon receptor.     

Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): exposure and toxicokinetics prior to and during pregnancy

Toxicokinetic studies were conducted following daily inhalation exposure to methanol vapor prior to and throughout pregnancy in adult female Macaca fascicularis monkeys. They were part of a larger study to investigate the effects of chronic methanol exposure on maternal reproductive performance and early offspring effects. In a two-cohort study design, 48 females (24/cohort) were assigned to parallel exposure groups at 0 (control), 200, 600, or 1800 ppm methanol vapor for approximately 2.5 h/day, 7 days/week throughout breeding and pregnancy. Blood methanol at 30 min postexposure was monitored biweekly. The time course for the clearance of blood MeOH concentrations following exposure was characterized on four occasions: twice during the prebreeding period and during mid- and late pregnancy. Average blood methanol concentrations at 30 min postexposure were 5, 11, and 35 microg/ml across all four toxicokinetic studies in the 200, 600 and 1800 ppm groups, respectively. Blood concentrations in the 200 ppm group were barely above basal (preexposure) blood methanol concentrations or those observed in the control group (approximately 3 microg/ml). Nonlinear elimination kinetics were observed in most of the 1800 ppm group females. There was a decrease in elimination half-life (7-20%) and an increase in clearance (30%) after 3-months of daily MeOH exposure compared to the initial exposure. There were no statistically significant changes in the first-order blood methanol half-life or clearance during pregnancy, but the mean distribution volume per kilogram body weight decreased by 22% and 17% in the 600 and 1800 ppm groups. Plasma formate levels did not differ between the methanol and control exposure groups. Plasma formate and serum folate concentrations increased slightly over the course of this study in both the exposed and control groups but these increases were not related to methanol exposure.     

Cost of delivering child immunization services in urban Bangladesh: a study based on facility-level surveys

This facility-based study estimated the costs of providing child immunization services in Dhaka, Bangladesh, from the perspective of healthcare providers. About a quarter of all immunization (EPI) delivery sites in Dhaka city were surveyed during 1999. The EPI services in urban Dhaka are delivered through a partnership of the Government of Bangladesh (GoB) and non-governmental organizations (NGOs). About 77% of the EPI delivery sites in Dhaka were under the management of NGOs, and 62% of all vaccinations were provided through these sites. The outreach facilities (both GoB and NGO) provided immunization services at a much lower cost than the permanent static facilities. The average cost per measles-vaccinated child (MVC), an indirect measure of number of children fully immunized (FIC-the number of children immunized by first year of life), was 11.61 U.S. dollars. If all the immunization doses delivered by the facilities were administered to children who were supposed to be immunized (FVC), the cost per child would have been 6.91 U.S. dollars. The wide gap between the cost per MVC and the cost per FVC implies that the cost of immunizing children can be reduced significantly through better targeting of children. The incremental cost of adding new services or interventions with current EPI was quite low, not significantly higher than the actual cost of new vaccines or drugs to be added. NGOs in Dhaka mobilized about 15,000 U.S. dollars from the local community to support the immunization activities. Involving local community with EPI activities not only will improve the sustainability of the programme but will also increase the immunization coverage.     

Cost and unit cost calculations using step-down accounting

There is paucity of unit cost data from low- and middle-income countries, although recent initiatives have emerged to help rectify this. The limited budgets assigned to health care facilities mean that health planners and managers must be able to account for the resources used in health facilities as well as use them efficiently. Step-down cost accounting (SDCA) offers a relatively simple method for generating cost and unit cost data at the facility level. However, to the best of our knowledge, there is a lack of clear and concise guidance on how to undertake SDCA. Therefore, this paper, using a worked example, illustrates the different steps involved to generate cost and unit costs for a small hospital.     

High-throughput gene mapping in Caenorhabditis elegans

Positional cloning of mutations in model genetic systems is a powerful method for the identification of targets of medical and agricultural importance. To facilitate the high-throughput mapping of mutations in Caenorhabditis elegans, we have identified a further 9602 putative new single nucleotide polymorphisms (SNPs) between two C. elegans strains, Bristol N2 and the Hawaiian mapping strain CB4856, by sequencing inserts from a CB4856 genomic DNA library and using an informatics pipeline to compare sequences with the canonical N2 genomic sequence. When combined with data from other laboratories, our marker set of 17,189 SNPs provides even coverage of the complete worm genome. To date, we have confirmed >1099 evenly spaced SNPs (one every 91 +/- 56 kb) across the six chromosomes and validated the utility of our SNP marker set and new fluorescence polarization-based genotyping methods for systematic and high-throughput identification of genes in C. elegans by cloning several proprietary genes. We illustrate our approach by recombination mapping and confirmation of the mutation in the cloned gene, dpy-18.     

Preload recruitable stroke work relationship in the right ventricle: simultaneous assessment using conductance catheter and sonomicrometry

OBJECTIVE: To examine the suitability of the conductance catheter technique for assessment of right ventricular systolic myocardial performance by using preload recruitable stroke work, we compared variables obtained simultaneously by conductance catheter and sonomicrometry dimension techniques. In addition, linearity of volume relationships was studied during rapid preload alteration by bicaval occlusion. DESIGN: Prospective animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized and ventilated swine (n = 9). INTERVENTIONS: Right intraventricular volumes were determined simultaneously by conductance catheter and sonomicrometry by using an ellipsoid shell subtraction model in open-chest swine. Animals were studied at the baseline state and under alterations of afterload, preload, and inotropy. Under each condition, steady-state recordings and transient bicaval occlusions were performed. Agreement of preload recruitable stroke work slope was assessed by using the Bland-Altman analysis, and second-order polynomials were fit to examine volume relationships during bicaval occlusions. MEASUREMENTS AND MAIN RESULTS: At steady state, the relationships for stroke-volumes and end-diastolic volumes were linear between the two methods. Altered physiologic conditions induced by the various interventions produced quantitatively similar changes in preload recruitable stroke work slope within an animal, although absolute values differed in some animals. Regression analysis of the preload recruitable stroke work slope revealed a significant intervention effect independent of the method used. During some bicaval occlusions, nonlinear relationships were observed similarly with both methods. CONCLUSIONS: These results suggest that changes in right ventricular systolic contractility assessed by the preload recruitable stroke work relationship were similar when measured by conductance catheter and sonomicrometry, although absolute values may differ in some animals.     

Vertically unstable pelvic fractures fixed with percutaneous iliosacral screws: does posterior injury pattern predict fixation failure?

OBJECTIVE: To measure the failure rate of percutaneous iliosacral screw fixation of vertically unstable pelvic fractures and particularly to test the hypothesis that fixations in which the posterior injury is a vertical fracture of the sacrum are more likely to fail than fixations with dislocations or fracture-dislocations of the sacroiliac joint. DESIGN: Retrospective review. SETTING: Level 1 trauma center. METHODS: All patients with pelvic fractures admitted between January 1, 1993, and December 31, 1998, were identified from the trauma registry. Hospital records were used to identify patients treated with iliosacral screws. Radiologic studies were examined to identify patients who had unequivocally vertically unstable pelvic fractures. Immediate postoperative and follow-up anteroposterior, inlet, and outlet radiographs from a minimum of 12 months postinjury were examined. Position, length, and numbers of iliosacral screws and any evidence of screw failure (eg, bending or breakage) were recorded. Residual postoperative displacement and late displacement of the posterior pelvis were measured. The main outcome measure was failure, defined as at least 1cm of combined vertical displacement of the posterior pelvis compared with immediate postoperative position. The main analysis was for association between fracture pattern and failure. Patient demographic data, iliosacral screw position, and anterior pelvic fixation method also were studied. RESULTS: The study group comprised 62 patients with unequivocally vertically unstable pelvic fractures in whom the posterior injury was treated with closed reduction and percutaneous iliosacral screw fixation. Of patients, 32 had dislocations or fracture-dislocations of the sacroiliac joint, and 30 had vertical fractures of the sacrum. Fixation failed in four patients, all with vertical sacral fractures and all within the first 3 weeks after surgery. These four patients required revision fixation. In two further cases with vertical sacral fractures, there was evidence that the fracture had only barely been held by the fixation, but these fractures healed, and follow-up radiographs did not meet the displacement criteria for failure. A vertical sacral fracture pattern was associated significantly with failure (Fisher exact test, P = 0.04); the excess risk of failure compared with sacroiliac joint injury was 13% (95% confidence interval 1% to 25%). There was no significant association between failure and anterior fixation method, iliosacral screw arrangement or length, or any demographic or injury variable. CONCLUSIONS: Percutaneous iliosacral screw fixation is a useful technique in the management of vertically unstable pelvic fractures, but a vertical sacral fracture should make the surgeon more wary of fixation failure and loss of reduction.     

Percutaneous radiofrequency ablation of pulmonary malignancies: combined treatment with brachytherapy

OBJECTIVE: The purpose of this article is to report the clinical experience and technical feasibility of percutaneous radiofrequency ablation in conjunction with brachytherapy, a novel approach in the treatment of lung neoplasms. Data from three patients with lung malignancies illustrate the expanding therapeutic indications of this minimally invasive intervention. CONCLUSION: Percutaneous radiofrequency ablation in conjunction with brachytherapy is a promising minimally invasive combination modality. It may be a treatment option for patients with primary, recurrent, or metastatic malignancies of the lung that are not amenable to surgery or further external beam radiation therapy.