Program- and method-related determinants of first DMPA use duration in rural Bangladesh

This article examines the determinants of first-time use durations of the injectable contraceptive Depo Medroxy Progesterone Acetate (DMPA) for rural Bangladeshi women. The method's side effects were defined by 200 first-time users in Matlab district during lengthy, open-ended interviews. Women with many children used the method longer than did women of low parity. Those who experienced side effects had shorter use durations than those who did not, and those who cited heavy bleeding as their main problem discontinued use soonest. Women whose husbands approved of family planning had significantly longer use durations than those whose husbands disapproved. Respondents who adopted DMPA because of perceived positive aspects of the drug used it longer than those who chose it for other reasons. Results of the study underscore the importance of viewing side effects in a specific social and cultural context. Expanded side-effects counseling for women and their husbands is needed.     

Variations of cardiac cycle length in patients with coronary heart disease before and after aortic coronary bypass surgery

It is well known that variations in cardiac cycle length or heart rates may be used for noninvasive evaluation of autonomic cardiovascular control. The investigation uses an original procedure. The data for analysis of cardiac cycle length variations (CCLV) are those obtained regularly at follow-up intervals, random 24-hour Holter 2-lead ECG recordings for 5 sec, and simultaneously calculated continuous sequence of mean heart rate. With the procedure, the correlations of CCLV with the parameters reflecting the early postoperative status of patients with CHD, including acute myocardial infarction, acute heart failure, rhythm and conduction disturbances, as well as age, operative stress, concurrent diseases. The findings are of both diagnostic and predictive value at subsequent stages of CHD treatment.     

Results of high-dose thoracic irradiation incorporating beam's eye view display in non-small cell lung cancer: a retrospective multivariate analysis

PURPOSE: To review the University of Michigan clinical experience in nonsmall cell lung cancer using high-dose thoracic irradiation (> or = 60 Gy) so that a starting dose for our prospective dose-escalation study could be determined. METHODS AND MATERIALS: Eighty-eight consecutive patients diagnosed with medically inoperable or locally advanced, unresectable nonsmall cell lung cancer were identified who were treated with thoracic irradiation alone to a minimum total dose of 60 Gy (uncorrected for lung density). All patients except four (95%) underwent computed tomography scanning for treatment planning that included beam's eye view display for tumor and critical structure localization. All patients were treated with standard fractionation in a continuous course to uncorrected total doses ranging from 60 to 74 Gy (median, 67.6 Gy). RESULTS: The median follow-up exceeds 24 months for all surviving patients (range, 12 to 78 months). The median survival time was 15 months, and the 2- and 3-year overall actuarial survival rates were 37% and 15%, respectively. Survival was significantly different between stage of disease (p = .004) and N-stage (p = .002) by univariate analysis. In a multivariate analysis, stage becomes the only characteristic significantly associated with outcome. The median time to local progression for 86 evaluable patients was 29 months. Stage (p = .0003), T-stage (p = .0095) and N-stage (p = .027) were significantly different with respect to local progression-free survival by univariate analysis. However, only stage was prognostic for local progression-free survival by multivariate analysis. There was no difference between large volume treatment (inclusion of the contralateral hilar and supraclavicular lymph nodes) and small volume treatment (exclusion of these elective nodal sites) with respect to local progression-free survival (p = .507) or survival (p = .520). With regard to dose, there was no significant difference between patients who received > 67.6 Gy and patients who received < or = 67.6 Gy with respect to local progression-free survival (p = .094) or survival (p = .142). Within the Stage III subgroup, local progression-free survival (p = .018) and survival (p = .061) were longer favoring the high-dose group of patients. Despite these doses, disease progression within the irradiated field was the predominant first site of treatment failure. CONCLUSION: This retrospective study has shown that it is feasible to deliver uncorrected tumor doses as high as 70 Gy using standard fractionation in NSCLC with acceptable morbidity. Local control remains a significant problem. These data indicate justification for a starting dose in a prospective radiation dose-escalation study.     

Evaluation of NR-LU-10 with the Neoprobe gamma detector in a mouse model

1. The effects of diethyl maleate (DEM) on the cytotoxicity of phenyl-hydroquinone (PHQ) and other hydroquinones were studied in freshly isolated rat hepatocytes. 2. Addition of PHQ (0.5 or 0.75 mM) to hepatocytes resulted in dose-dependent cell death accompanied by the abrupt depletion of both GSH and protein thiols and the accumulation of phenyl-benzoquinone (PBQ). 3. Pretreatment with DEM (1.25 mM), which causes an abrupt depletion of cellular GSH in hepatocytes, delayed the onset of PHQ-induced cytotoxicity. The delay correlated with inhibition of PBQ formation. 4. Although the pH of the cell suspension was increased slightly (mean pH 0.18) by incubation under carbogen flow, the addition of DEM to the cell suspension inhibited both the increase in pH and the formation of PBQ from PHQ. 5. In hepatocyte suspensions without DEM, PHQ cytotoxicity was dependent on pH, and toxicity was associated with oxidation of PHQ and accumulation of PBQ. 6. Among other hydroquinones (0.5 mM), tert-butyl-hydroquinone-induced cytotoxicity was decreased by DEM (1.25 mM), but DEM did not affect the cytotoxicity of 2,5-di(tert-butyl)-1,4-benzohydroquinone. 7. PHQ-induced cytotoxicity correlated with the accumulation of PBQ in the cell, and the inhibition of PHQ-induced cytotoxicity by DEM correlated with pH-dependent changes in PBQ formation.     

The effect of converting from pravastatin to simvastatin on the pharmacodynamics of warfarin

Glycosylated amino acids and glycosylated human serum albumin reduce nitrite to nitric oxide under anaerobic conditions. The amount of nitric oxide produced was recorded by generation of nitrosoHb from deoxyHb. Without preincubation after the addition of sodium nitrite, glucose or a mixture of glucose with amino acid or serum albumin did not cause spectrophotometrically detectible transformation of deoxyHb into nitrosoHb. The generation of NO increased with an increase in content of colored "final" products of amino acid and serum albumin glycosylation in the incubation mixture. The incubation of blood plasma of patients with diabetes mellitus with nitrite also resulted in the increased production of NO as compared to blood plasma of healthy subjects. During the incubation of healthy subjects' blood plasma with nitrite a small amount of NO was produced. The removal of low-molecular-weight compounds was accompanied by a significantly decreased generation of NO by blood plasma.     

The crystal structure of the immunity protein of colicin E7 suggests a possible colicin-interacting surface

The immunity protein of colicin E7 (ImmE7) can bind specifically to the DNase-type colicin E7 and inhibit its bactericidal activity. Here we report the 1.8-angstrom crystal structure of the ImmE7 protein. This is the first x-ray structure determined in the superfamily of colicin immunity proteins. The ImmE7 protein consists of four antiparallel alpha-helices, folded in a topology similar to the architecture of a four-helix bundle structure. A region rich in acidic residues is identified. This negatively charged area has the greatest variability within the family of DNase-type immunity proteins; thus, it seems likely that this area is involved in specific binding to colicin. Based on structural, genetic, and kinetic data, we suggest that all the DNase-type immunity proteins, as well as colicins, share a "homologous-structural framework" and that specific interaction between a colicin and its cognate immunity protein relies upon how well these two proteins' charged residues match on the interaction surface, thus leading to specific immunity of the colicin.     

Islet amyloid polypeptide in patients with pancreatic cancer and diabetes

Population-based psychiatric admission rates vary across geographic areas, but reasons for this variation are unknown. Insofar as Community Mental Health Centers (CMHCs) provide outpatient services that may deter the need for hospitalization, the presence and structural characteristics of CMHCs may have an impact on a population's psychiatric admission rates. This study uses small area analysis to examine how general hospital psychiatric admission rates are associated with CMHC characteristics. Based on a survey of all CMHCs in Iowa and corresponding small area variation data, it was found that population admission rates were higher in areas closer to the CMHC and lower in outlying catchment areas, adjusting for age, sex, and urban/rural differences in populations. There was little evidence that differences in staffing and service variables influenced admission rates, although greater CMHC staff coverage by social workers and psychiatric residents was associated with lower admission rates. The results suggest that CMHCs do not lower an area's hospitalization rate, and in fact, the presence of CMHCs may promote a "supplier-induced demand" phenomenon of higher admissions.     

Thecal cell-granulosa cell interactions involve a positive feedback loop among keratinocyte growth factor, hepatocyte growth factor, and Kit ligand during ovarian follicular development

Interactions between mesenchymal-derived thecal cells and epithelial-derived granulosa cells are essential for follicular development in the ovary. These mesenchymal-epithelial cell interactions are in part mediated by keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and Kit ligand (KL). This study investigates the hypothesis that thecal cell-derived growth factors (e.g. KGF and HGF) regulate granulosa cell function, and granulosa cell-derived growth factors (e.g. KL) regulate thecal cell function. Gonadotropin regulation of this cell-cell interaction is also examined. Sensitive quantitative RT-PCR assays were used to analyze gene expression of KGF, HGF, and KL in the ovary. Thecal cell-derived KGF and HGF stimulated KL expression in bovine granulosa cells. Granulosa cell-derived KL stimulated KGF and HGF expression in bovine thecal cells. These results suggest that thecal and granulosa cells interact in a positive feedback loop mediated by KGF, HGF, and KL. Previous studies have suggested that gonadotropins (i.e. FSH and LH) regulate locally produced growth factor expression in the ovary. Treatment of bovine granulosa cells with FSH and hCG (a LH agonist) directly stimulated KL expression. The LH agonist hCG was also found to stimulate both KGF and HGF expression in thecal cells. The actions of gonadotropins on follicular development may in part be indirectly regulated by KL, KGF, and HGF expression. A novel positive feedback loop was identified between thecal cells and granulosa cells that is mediated by KL, KGF, and HGF. Thecal cell-derived KGF and HGF can stimulate granulosa cell-derived KL expression, and KL, in turn, can stimulate thecal cell-derived KGF and HGF expression. Combined observations support the hypothesis that mesenchymal-epithelial cell interactions between thecal and granulosa cells can play a significant role during ovarian follicular development and mediate gonadotropin actions.     

Posturography does not test vestibulospinal function

The clinical usefulness of posturography is unknown, despite its costing more than +500 per test in some areas of the United States, including Boston. We cross-sectionally and prospectively studied blinded vestibulo-ocular and vestibulospinal tests from 29 stable patients with chronic vestibular hypofunction; 22 patients were affected bilaterally (BVH), and 7 were affected unilaterally (UVH). Vestibulo-ocular function was assessed by electronystagmographic caloric stimulation and sinusoidal vertical axis rotation gains at 0.05 Hz. Vestibulospinal function was assessed by moving-platform and visualsurround posturography sensory organization tests (SOTs), paced and free gait in a gait laboratory, and clinical tests of timed gait and standing. Posturography SOT moving-platform tests 4 through 6, designed to assess vestibular function, correlated significantly (r < or = 0.72, P > or = 0.01) with vestibulo-ocular tests in 5 of 6 comparisons among BVH patients. Posturography SOT results, however, correlated poorly with other vestibulospinal measures: correlations were statistically significant for only 7 of 18 comparisons with clinical balance and gait function (r < or = 0.69, P > or = 0.01) and with 2 of 12 comparisons for gait laboratory dynamic stability measures (r < or = 0.55, P > or = 0.01) among the BVH patients. When both the platform and visual surround moved (SOT 6), however, correlations were statistically significant with static standing clinical measures (r = 0.51 to 0.69, P < 0.01) and with whole-body maximum moment arm during paced gait (r = 0.55, P < 0.01). Posturography scores for the UVH patients did not significantly correlate with any vestibulo-ocular or other vestibulospinal measures. These data indicate that among patients with BVH posturography SOT scores relate at best modestly with accepted measure of vestibulo-ocular function, less well with clinical measures of balance control, and poorly with dynamic gait-performance measures. We conclude that posturography SOT does not assess vestibulospinal function.