Quantitative distribution of six amino acids in rat retinal layers

Concentrations of glutamate, aspartate, glutamine, glycine, GABA, and taurine were determined in samples microdissected from rat retinal layers and assayed by HPLC. Glutamate and glutamine were relatively high in the inner nuclear (INL) and ganglion cell (GCL) layers; aspartate was relatively high in the outer nuclear layer (ONL), outer plexiform layer, and INL. Distributions of glutamate and aspartate did not correlate well with those of enzymes involved in their metabolism. Glycine and GABA were highest in the inner plexiform layer, with increasing concentrations through the INL, and were relatively high in the GCL. Taurine was highest in the ONL.     

Community-oriented primary care in action: a Dallas story

Dallas County, Texas, is the site of the largest urban application of the community-oriented primary care (COPC) model in the United States. We summarize the development and implementation of Dallas's Parkland Health & Hospital System COPC program. The complexities of implementing and managing this comprehensive community-based program are delineated in terms of Dallas County's political environment and the components of COPC (assessment, prioritization, community collaboration, health care system, evaluation, and financing). Steps to be taken to ensure the future growth and development of the Dallas program are also considered. The COPC model, as implemented by Parkland, is replicable in other urban areas.     

Review of lateral orbital wall ossifying fibroma

Significant histological overlap exists between fibro-osseous lesions and diagnosis is made on a clinicopathological basis. Ossifying fibroma is a benign fibro-osseous neoplasm of the jaw and craniofacial complex that has generated a degree of controversy regarding diagnosis and classification, especially with respect to the psammomatoid variant. Orbital lesions mainly arise from the paranasal sinuses affecting the medial or inferior orbital wall. Lateral orbital wall ossifying fibroma is, therefore, a rare condition with only a single previous case report. We present a second case of lateral orbital wall ossifying fibroma and a review of the associated literature.     

Carvedilol for children and adolescents with heart failure: a randomized controlled trial

Context  Although -blockers improve symptoms and survival in adults with heart failure, little is known about these medications in children and adolescents. Objective  To prospectively evaluate the effects of carvedilol in children and adolescents with symptomatic systemic ventricular systolic dysfunction. Design, Setting, and Participants  A multicenter, randomized, double-blind, placebo-controlled study of 161 children and adolescents with symptomatic systolic heart failure from 26 US centers. In addition to treatment with conventional heart failure medications, patients were assigned to receive placebo or carvedilol. Enrollment began in June 2000 and the last dose was given in May 2005 (each patient received medication for 8 months). Interventions  Patients were randomized in a 1:1:1 ratio to twice-daily dosing with placebo, low-dose carvedilol (0.2 mg/kg per dose if weight <62.5 kg or 12.5 mg per dose if weight 62.5 kg), or high-dose carvedilol (0.4 mg/kg per dose if weight <62.5 kg or 25 mg per dose if weight 62.5 kg) and were stratified according to whether each patient's systemic ventricle was a left ventricle or not. Main Outcome Measures  The primary outcome was a composite measure of heart failure outcomes in patients receiving carvedilol (low- and high-dose combined) vs placebo. Secondary efficacy variables included individual components of this composite, echocardiographic measures, and plasma b-type natriuretic peptide levels. Results  There was no statistically significant difference between groups for the composite end point based on the percentage of patients who improved, worsened, or were unchanged. Among 54 patients assigned to placebo, 30 improved (56%), 16 worsened (30%), and 8 were unchanged (15%); among 103 patients assigned to carvedilol, 58 improved (56%), 25 worsened (24%), and 20 were unchanged (19%). The rates of worsening were lower than expected. The odds ratio for worsened outcome for patients in the combined carvedilol group vs the placebo group was 0.79 (95% CI, 0.36-1.59; P = .47). A prespecified subgroup analysis noted significant interaction between treatment and ventricular morphology (P = .02), indicating a possible differential effect of treatment between patients with a systemic left ventricle (beneficial trend) and those whose systemic ventricle was not a left ventricle (nonbeneficial trend). Conclusions  These preliminary results suggest that carvedilol does not significantly improve clinical heart failure outcomes in children and adolescents with symptomatic systolic heart failure. However, given the lower than expected event rates, the trial may have been underpowered. There may be a differential effect of carvedilol in children and adolescents based on ventricular morphology. Trial Registration  clinicaltrials.gov Identifier: NCT00052026      

The response of leptin, interleukin-6 and fat oxidation to feeding in weight-losing patients with pancreatic cancer

At baseline, weight-losing pancreatic cancer patients (n=7) had lower leptin (P<0.05) but higher cortisol, interleukin-6, resting energy expenditure and fat oxidation than healthy subjects (n=6, P<0.05). Over a 4 h feeding period, the areas under the curve for glucose, cortisol and interleukin-6 were greater (P<0.05), but less for leptin in the cancer group (P<0.05). Therefore, it would appear that low leptin concentrations, increased fat oxidation and insulin resistance are associated with increased concentrations of cortisol and interleukin-6 in weight-losing patients with pancreatic cancer.     

Efficacy and safety of erythropoiesis-stimulating proteins in myelodysplastic syndrome: a systematic review and meta-analysis

OBJECTIVE: The objective was to assess the efficacy and safety of erythropoiesis-stimulating proteins (ESPs) in anemia of myelodysplastic syndrome (MDS). METHOD: A systematic review and meta-analysis was conducted covering English-language studies published from 1980 to December 2005. RESULTS: Fifty-nine studies qualified: five controlled trials (n = 354), all epoetin versus control (EvC); 51 epoetin single-arm studies (n = 1,650); and three darbepoetin single-arm studies (n = 102). In the EvC studies, epoetin patients demonstrated a significant advantage over controls in terms of hemoglobin (Hb) response (odds ratio, 5.2; 95% confidence interval, 2.5-10.8). Hb response was 48.1% in single-arm darbepoetin studies, 32.1% in epoetin single-arm studies, and 27.3% in EvC studies. Major Hb response averaged 38.8% in darbepoetin studies, 24.5% in epoetin single-arm studies, and 11.4% in EvC studies. Stratified analyses suggest that lower baseline erythropoietin levels, longer treatment durations, and concurrent iron may be associated with greater Hb response to ESPs. None of the analyzable predictors of Hb response (gender, baseline Hb, ESP type, and ESP duration) were significant in meta-regression analyses. In the few studies with quality-of-life measures, ESP groups attained a pre-post change (Functional Assessment of Cancer Therapy - Fatigue) that exceeded minimum clinically important differences. Selected adverse event rates did not differ between the epoetin and darbepoetin groups. CONCLUSION: Published studies suggest that ESPs are efficacious in anemia of MDS. Hb response appears higher in darbepoetin patients than in epoetin patients, and safety appears comparable, but darbepoetin data are sparse, and there are as yet no direct comparison studies.     

Long term follow-up of c-myc, p53 and proliferation measurements in malignant melanoma.

AIMS: We report a prospective study examining the prognostic significance of the c-myc oncoprotein, p53 tumour suppressor gene and proliferation rate measurements in malignant melanoma. METHODS: Flow cytometry (FCM) was used to measure the expression of c-myc, p53 and proliferation parameters in patients who had received an injection of the thymidine analogue bromodeoxyuridine prior to surgery. RESULTS: Sixty-seven patients had successful FCM measurements of the three parameters. c-myc was detected in 97% of patients with a median cell positivity of 62%. The median p53 positivity was 13%. The median potential doubling time (T(pot)) of the tumours wasf 9.4 days. In univariate analysis, each of the parameters showed an association with survival in metatstatic disease with rapid proliferation (p=0.006) or overexpression of c-myc (p=0.038) related to poor survival whereas increased positivity for p53 predicted better survival (p=0.013). CONCLUSIONS: These data indicate that laser cytometric technology can be used to obtain quantitative data on oncoproteins expression and cell proliferation rates in clinical samples of malignant melanoma.