Early developmental 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure decreases chick embryo heart chronotropic response to isoproterenol but not to agents affecting signals downstream of the beta-adrenergic receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) causes cardiovascular toxicity in laboratory animals, including alteration in several processes in which beta-adrenergic receptor (beta-AR) signaling plays important roles. Thus, our laboratory investigated the effects of TCDD on beta-AR expression and signal transduction. Fertile chicken eggs were injected with vehicle (corn oil), 0.24 or 0.3 pmol TCDD/g egg on incubation day 0 (D0) or D5. On D10, heart function was assessed by ECG in ovo. Exposure to TCDD increased the incidence of arrhythmias and decreased the positive chronotropic responsiveness of the heart to isoproterenol. The reduced beta-AR responsiveness was, in part, independent of any overt morphological changes in the heart as chick embryos exposed to TCDD on D5 displayed an intermediate responsiveness to beta-AR agonist in the absence of the dilated cardiomyopathy observed in chick embryos exposed to TCDD on D0. TCDD did not decrease the chronotropic response of the heart to agents that stimulate signals downstream of the beta-AR. In fact, TCDD-exposed embryos were more sensitive than controls to forskolin, increasing heart rates (HR) 21.8 +/- 3.5 beats per min (bpm) above baseline versus control values at 6.3 +/- 2.7 bpm above baseline. TCDD exposure also augmented the negative chronotropic response of the heart to verapamil, decreasing HR -23.2 +/- 7.4 bpm relative to baseline versus control embryos at -12.7 +/- 5.9 bpm below baseline. Finally, the mean cardiac beta1-AR mRNA expression in D10 embryos was not significantly altered by exposure to TCDD on D0. These findings establish that a functional end point of the developing chick heart is sensitive to TCDD exposure and that the TCDD-induced reduction in beta-AR responsiveness may result from alterations in signal transduction upstream of adenylyl cyclase.     

Public–Private Collaboration in Health and Human Service Delivery: Evidence from Community Partnerships

The collaboration among public–private partnerships that applied to the Community Care Network (CCN) demonstration program of the Hospital Research and Educational Trust is examined. These partnerships link broad-based community coalitions with health and human service providers in efforts to improve community health and local service delivery. Although they willingly collaborated in identifying community health needs, coordinating services, and reporting to the community, partnership participants showed less alacrity in joining forces to reduce redundancy and increase efficiency. Such patterns suggest that organizations might best profit from working together on activities that maintain existing power relations and that have the potential to add prestige and attract new clients. Collaboration in these areas may be essential to building a foundation of trust that leads to future cooperation in more sensitive areas.     

HLA-DR expression in macaque neuroendothelial cells in vitro and during SIV encephalitis

HLA-DR expression in neuroendothelial cells (NEC) was studied during the course of SIV encephalitis in rhesus monkeys. HLA-DR determinants were detected on NEC in monkeys with SIV encephalitis, but not in control animals. In situ hybridization with an SIV probe indicated that HLA-DR expression was not a consequence of SIV replication within NEC. Cultured rhesus NEC stimulated with gamma interferon expressed HLA-DR to a higher degree than cultured brain fibroblasts or astrocytes. These data support the contention that NEC participate in retrovirus-induced inflammation and autoimmunity within the central nervous system.     

Genetic determinants of statin intolerance

Background  

Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK) concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the COQ2 gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in COQ2 would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint.     

Right superficial femoral artery to superior vena cava graft using a polytetrafluroethylene graft: a new technique in a complicated dialysis access patient.

Sir, The expansion of haemodialysis includes older patients withcomorbidities, poor quality vessels, unsuitable for transplantationor peritoneal dialysis. Vascular access complications accountfor 20% of hospital admissions [1]. With exhausted sites inupper extremities, unusual sites for arteriovenous grafts formationare used [2]. The     

The Development and Teaching of the Ethical Principles and Guidelines for Family Scientists*

This article describes the development of the Ethical Principles and Guidelines for Family Scientists that the National Council on Family Relations Board of Directors unanimously approved. Furthermore, it discusses the importance of ethics education for family professionals and provides suggestions for educators. Finally, the ethical principles and guidelines are delineated. We argue that the development of a scholarship on ethics education is important for current and future family scientists.     

Growth hormone benefits children with 18q deletions

Most individuals with constitutional deletions of chromosome 18q have developmental delays, dysmyelination of the brain, and growth failure due to growth hormone deficiency. We monitored the effects of growth hormone treatment by evaluating 23 individuals for changes in growth, nonverbal intelligence quotient (nIQ), and quantitative brain MRI changes. Over an average of 37 months, the treated group of 13 children had an average nIQ increase of 17 points, an increase in height standard deviation score of 1.7, and significant change in T1 relaxation times in the caudate and frontal white matter. Cognitive changes of this magnitude are clinically significant and are anticipated to have an effect on the long-term outcomes for the treated individuals.     

Serum LDH level as a clue to the diagnosis of histoplasmosis

The purpose of this study was to determine whether serum lactate dehydrogenase (LDH) level could be used as an adjunct clinical marker to differentiate between histoplasmosis and Pneumocystis carinii pneumonia (PCP). In a retrospective, case-controlled study, 30 patients with a diagnosis of histoplasmosis (all but 1 with disseminated disease) were compared with 120 patients with PCP (33 patients with definitive PCP, 87 with presumed PCP). Groups were matched for CD4+ lymphocyte counts, sex, and year of diagnosis. The mean LDH level for patients with histoplasmosis was 1068 +/- 197 IU/L; for PCP, it was 375 +/- 23. An LDH level of more than 450 IU/L was 9.33 times more likely to be associated with a diagnosis of histoplasmosis than with PCP (odds ratio [OR], 9.33; 95% confidence interval [CI], 3.50-25.47; P < .01), and an LDH level of more than 600 IU/L was 9.41 times more likely to be so (OR, 9.41; 95% CI, 3.43-26.31; P < .01). An LDH level of 450 IU/L or greater had a sensitivity and specificity of 70% and 80%, respectively; a value of 600 IU/L or greater had sensitivity and specificity of 50% and 89%. Thus, serum LDH levels of 600 IU/L or greater are suggestive of histoplasmosis rather than PCP in appropriate clinical settings. Serum LDH may serve as an adjunct laboratory marker in the diagnosis of histoplasmosis. Elevated levels may prompt the physician to look for a diagnosis other than PCP early in the course of the illness.     

Improving HIV surveillance in Victoria: the role of the "detuned" enzyme immunoassay

Between 1999 and 2000, new diagnoses of HIV in Victoria (Australia) rose by 41%, from 140 to 197. In this time period, sera from new HIV diagnoses were tested using the Organon Teknika "detuned" enzyme immunoassay (EIA). We compared the results of the detuned EIA with incident infections defined by surveillance (on the basis of a previous negative or indeterminate HIV test and/or a seroconversion illness within the 12 months preceding HIV diagnosis). Of 317 specimens, 97 (31%) incident infections and 114 (36%) recent infections were detected using surveillance and detuned EIA, respectively. The detuned assay misclassified 11 cases with AIDS and 2 cases with CD4 counts < or = 200 micro3 (probable long-standing infections) as recent infections and was unable to identify 31 (32%) of 97 cases previously classified as incident cases by surveillance. The assay detected an extra 35 recent infections that were previously classified as nonincident by surveillance. By combining the detuned assay and surveillance, 132 (42%) incident infections were identified from 317 specimens, 36% more than surveillance alone. We recommend that a detuned assay or similar test become part of the routine strategy to identify incident infections in Victoria. Incident infections provide important information for targeting prevention strategies and the opportunity to interrupt ongoing viral transmission.     

Effect of hemoglobin concentration variation on the accuracy and precision of glucose analysis using tissue modulated, noninvasive, in vivo Raman spectroscopy of human blood: a small clinical study

Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p<0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subject's hemoglobin concentration was also observed.