Characteristics of Hidden Status Among Users of Crack, Powder Cocaine, and Heroin in Central Harlem

This article analyzes hidden status among crack, powder cocaine, and heroin users and setters, in contrast to more accessible users/sellers. Several sampling strategies acquired 657 users (N=559) and sellers (N=98). Indicators of hidden status were those who (1) paid rent in full in the last 30 days, (2) used nonstreet drug procurement. (3) had legal jobs, and (4) earned $1,000 or more in legal income in the last 30 days. Nearly half had at least one indicator: approximately 16% of users/sellers had two to four indicators. In logistic regression analyses, those who had not panhandled in the last 30 days, those who had used powder cocaine in the last 30 days, and those never arrested were the most likely to have hidden status, whether the analysis predicted those having any indicators or those having two to four indicators. The four indicators begin to operationally define hidden status among users of cocaine and heroin.     

Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats

3,4-Methylenedioxymethamphetamine damages fine serotonergic fibers and nerve terminals in adult organisms. Developing animals seem to be less susceptible to this effect, possibly due to a lack of drug-induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 h after each of twice-daily MDMA (10 mg/kg s.c.) or saline injections administered from postnatal days 1–4. Other drug-treated and control litters were maintained at normothermic temperatures following injection. Changes in forebrain serotonergic innervation were assessed at postnatal day 25 (serotonin transporter binding and serotonin levels), postnatal day 60 (serotonin transporter binding), and 9 months of age (serotonin transporter immunohistochemistry). We also determined the influence of MDMA treatment on apoptotic activity by means of immunohistochemistry for cleaved caspase-3 at postnatal day 5. The hippocampus showed significant MDMA-related reductions in serotonergic markers at postnatal day 25 and postnatal day 60. At 9 months, there was no effect of prior MDMA exposure on serotonin transporter-immunoreactive fiber density in the hippocampus; however, significant reductions in fiber density were observed in two neocortical areas and a hyperinnervation was found in the caudate-putamen and nucleus accumbens shell. MDMA treatment also produced a two-fold increase in the number of cleaved caspase-3-immunoreactive cells in the rostral forebrain and hippocampus. All of these effects were completely independent of pup body temperature. These findings demonstrate that neonatal MDMA administration exposure stimulates apoptotic cell death in various forebrain areas and also leads to a long-term reorganization of the forebrain serotonergic innervation. Consequently, offspring of MDMA-using women may be at heightened risk for abnormal neural and behavioral development.     

Commutability of the CRM 470 C-reactive protein value in the Dade Behring N High Sensitivity CRP assay.

Certified Reference Material 470 (CRM 470) demonstrates commutability with both the manufacturer's calibrator and with dilutions of serum pools in the Dade Behring N High Sensitivity assay for C-reactive protein (CRP). Both regression and back calibration show similar nonlinearity for all materials, largely due to the method of calibration curve fitting used in this assay. Significant differences in values among the currently available commercial assays can be largely overcome by using appropriate calibration curve fitting and the recommended value transfer protocol, which includes a minimum of two assay runs on each of at least 3 separate days, with weight correction of all reconstitutions and dilutions. An initial weight-corrected dilution should be made each day because of the relatively high level of CRP in CRM 470. In our opinion, the degree of nonlinearity, imprecision, and differences in values in currently available assays renders the use of fixed clinical decision cut-points questionable for high-sensitivity CRP. An alternative approach is suggested.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Building bridges between neural models and complex decision making behaviour.

Diffusion processes, and their discrete time counterparts, random walk models, have demonstrated an ability to account for a wide range of findings from behavioural decision making for which the purely algebraic and deterministic models often used in economics and psychology cannot account. Recent studies that record neural activations in non-human primates during perceptual decision making tasks have revealed that neural firing rates closely mimic the accumulation of preference theorized by behaviourally-derived diffusion models of decision making. This article bridges the expanse between the neurophysiological and behavioural decision making literatures specifically, decision field theory [Busemeyer, J. R. & Townsend, J. T. (1993). Decision field theory: A dynamic-cognitive approach to decision making in an uncertain environment. Psychological Review, 100, 432-459], a dynamic and stochastic random walk theory of decision making, is presented as a model positioned between lower-level neural activation patterns and more complex notions of decision making found in psychology and economics. Potential neural correlates of this model are proposed, and relevant competing models are also addressed.     

P07Reduction of Allogeneic Red Cell Transfusion using Autologous Blood Cell Salvage in Knee Arthroplasty

Recent Hospital Transfusion Committee (HTC) audit at the Royal Bournemouth Hospital (RBH) confirmed an allogeneic red cell transfusion rate of 20% for primary Total Knee Replacement (TKR). Current policy at RBH states that when blood stocks reach 67% of normal (amber alert) then surgery with a >20% likelihood of blood transfusion will be cancelled. At current transfusion rates this would include primary TKR. Recent studies have shown a reduction in allogeneic transfusion rates when autologous transfusion drains are utilized. The purpose of this study was to see whether the current rate of allogeneic transfusion could be reduced with the introduction of the CellTransTM Autologous Knee Drainage Blood Transfusion System (ABT) in TKR at RBH. Over a 3 month period all patients undergoing primary, bilateral or revision knee arthroplasty received an ABT. Demographic data was collected from the orthopaedic pre‐assessment clinic. Following surgery further data was collected relating to volume of blood loss into the drain, volume of autologous blood re‐transfused, units of allogeneic blood required and the transfusion trigger, postoperative haemoglobin levels, infection rates and length of stay in hospital. We then compared this data set with retrospective data. Of 170 patients undergoing knee arthroplasty 141 received the ABT. The data collected was compared retrospectively with 169 patients from the previous 3 month period. We demonstrated a reduction in transfusion rates of 13% for primary TKR, 42% for bilateral TKR and 57% for revision TKR with the use of the ABT. In addition we demonstrated a reduction in total allogeneic blood use (99 units to 26 units) and a reduction in mean length of stay in hospital (8.6 days to 7.5 days) with the ABT. Further analysis of the data collected showed a 46% reduction in the allogeneic transfusion rate and a reduction in total allogeneic blood usage (99 units to 9 units) of anaemic patients presenting for surgery. This study has demonstrated a dramatic reduction in allogeneic blood transfusion rates with the use of the CellTransTM Autologous Blood Transfusion System. We have also shown a reduction in length of stay in hospital. Prior to the study primary total knee replacement would have been cancelled during times of limited blood availability (amber alert). The use of the ABT is good for the patient in reducing the need for allogeneic blood, and in addition has demonstrated a significant cost saving due to the reduced blood usage and potential prevention of cancelled operation lists.     

Platelet adherence to cardiac and noncardiac endothelial cells in culture: lack of a prostacyclin effect

Cardiac tissues show a propensity to develop nonbacterial thrombotic endocarditis, a meshwork of platelets and fibrin. This lesion may cause a predisposition to subsequent colonization by circulating microorganisms, leading to infective endocarditis. We measured platelet adherence in vitro to cultured endothelial cells derived from the porcine aortic valve and ascending aorta. We found that valvular endothelial cells showed a twofold to threefold higher adherence than ascending aortic endothelial cells of chromium 51-labeled platelets in the presence of proteolytically active thrombin. This finding did not correlate with endothelial prostacyclin release: cardiac valve endothelial cells released more prostacyclin than did, ascending aortic cells, exogenous prostacyclin had no effect on thrombin-stimulated adherence, and aspirin inhibition of endothelial prostacyclin synthesis showed no effect on platelet adherence. Fixation of platelets abolished thrombin-stimulated adherence; fixation of endothelial cells had minimal effect. We suggest that these differences may contribute to the propensity of the cardiac valve to develop nonbacterial thrombotic endocarditis.     

Wrist ratio correlation with carpal tunnel syndrome in industry

Employees from a large midwestern automobile manufacturing plant completed a preemployment evaluation which included a personal and family history, physical examination, and wrist ratio determinations obtained by dividing the anteroposterior diameter by the mediolateral diameter of the wrist. Over a 3-year period, 80 of these employees who developed symptoms compatible with carpal tunnel syndrome within 4-12 months of employment were entered into the study and were evaluated with standard electrodiagnostic techniques. The symptoms included nocturnal hand pain, paresthesia and weak grasp. Thirty-nine of the 80 employees had wrist ratios equal to or greater than 0.70. Twenty-four percent of the employees with wrist ratios less than 0.70 had abnormal electrodiagnostic studies compared with 74% of employees with wrist ratios greater than or equal to 0.70. Regression analysis performed on the data revealed a significant positive correlation between distal median motor latency and wrist ratio (P = 0.001). The study suggests the practical value of wrist ratio determination in job placement.