Research bronchoscopies do not adversely affect HIV-infected individuals' future health-care decisions

STUDY OBJECTIVES: Asymptomatic HIV-infected individuals are increasingly recruited for studies involving invasive procedures such as bronchoscopy. We sought to determine the response to and outcome of a request for a research bronchoscopy in HIV-positive individuals with no respiratory disease, and whether this would adversely affect future decisions to have a medically indicated bronchoscopy. DESIGN AND SETTING: Prospective, semistructured, questionnaire-based study in a London teaching hospital HIV outpatient clinic. PARTICIPANTS: One hundred and seven consecutive HIV-infected eligible individuals. Thirty-one healthy volunteers served as a control group for the subjective response to bronchoscopy. MAIN OUTCOME MEASURES: Subjects' attitudes and responses to requests for bronchoscopy and subsequent behavior when they required medically indicated bronchoscopy. RESULTS: Seventy-five patients (70%) agreed to the procedure in principle, predominantly for altruistic reasons. Thirty-nine subjects underwent bronchoscopy. Five percent found it worse than expected; and 79% agreed to another research bronchoscopy (performed in 11 subjects approximately 2 years later). All patients said they would undergo bronchoscopy again for diagnostic purposes (required in seven during the study). When compared to a healthy volunteer population within the same study, postbronchoscopy symptoms were similar in frequency although somewhat different in nature. Subjects felt that a clear explanation of what was involved enhanced their participation in this research. CONCLUSIONS: Invasive research procedures such as bronchoscopy can be performed and are repeatable in a healthy HIV-infected population. Performance of procedures for research purposes does not appear to adversely affect future health-care decisions.     

Role of G protein betagamma subunits in muscarinic receptor-induced stimulation and inhibition of adenylyl cyclase activity in rat olfactory bulb

In the olfactory bulb, muscarinic receptors exert a bimodal control on cyclic AMP, enhancing basal and Gs-stimulated adenylyl cyclase activities and inhibiting the Ca2+/calmodulin- and forskolin-stimulated enzyme activities. In the present study, we investigated the involvement of G protein betagamma subunits by examining whether the muscarinic responses were reproduced by the addition of betagamma subunits of transducin (betagamma(t)) and blocked by putative betagamma scavengers. Membrane incubation with betagamma(t) caused a stimulation of basal adenylyl cyclase activity that was not additive with that produced by carbachol. Like carbachol, betagamma(t) potentiated the enzyme stimulations elicited by vasoactive intestinal peptide and corticotropin-releasing hormone. RT-PCR analysis revealed the expression of mRNAs encoding both type II and type IV adenylyl cyclase, two isoforms stimulated by betagamma synergistically with activated Gs. In addition, betagamma(t) inhibited the Ca2+/calmodulin- and forskolin-stimulated enzyme activities, and this effect was not additive with that elicited by carbachol. Membrane incubation with either one of two betagamma scavengers, the GDP-bound form of the alpha subunit of transducin and the QEHA fragment of type II adenylyl cyclase, reduced both the stimulatory and inhibitory effects of carbachol. These data provide evidence that in rat olfactory bulb the dual regulation of cyclic AMP by muscarinic receptors is mediated by betagamma subunits likely acting on distinct isoforms of adenylyl cyclase.     

Cholesterol oxides accumulate in human cataracts

Glucocorticoids induce hyperinsulinemia, hyperglycemia, and depress glucose transport by aortic endothelium. High glucocorticoid doses are used for many diseases, but with unknown effects on brain glucose transport or metabolism. This study tested the hypothesis that glucocorticoids affect glucose transport or metabolism by brain microvascular endothelium. Male rats received dexamethasone (DEX) s.c. with sucrose feeding for up to seven days. Cerebral microvessels from rats treated with DEX/sucrose demonstrated increased GLUT1 and brain glucose extraction compared to controls. Glucose transport in vivo correlated with hyperinsulinemia. Pre-treatment with low doses of streptozotocin blunted hyperinsulinemia and prevented increased glucose extraction induced by DEX. In contrast, isolated brain microvessels exposed to DEX in vitro demonstrated suppression of 2-deoxyglucose uptake and glucose oxidation. We conclude that DEX/sucrose treatment in vivo increases blood-brain glucose transport in a manner that requires the effects of chronic hyperinsulinemia. These effects override any direct inhibitory effects of either hyperglycemia or DEX.     

Prenatal diagnosis of trisomy 13 on fetal cells obtained from maternal blood after minor enrichment

In a pilot study to establish fetal nucleated red blood cell (NRBC) detection in maternal blood, trisomy 13 was diagnosed by FISH analysis at 11 weeks' gestation. The NRBCs were detected after a single-step ficoll density gradient enrichment. In blood samples taken both before and after CVS, 52 and 80 NRBCs, respectively, were found to be positive for fetal haemoglobin. In 47 per cent of these cells, FISH analysis for X and Y chromosomes confirmed the fetal sex. Moreover, 48 per cent of these NRBCs showed three fluorescent signals for a chromosome 13 probe, which confirmed the diagnosis of trisomy 13, previously detected at CVS karyotyping. This is the first report of non-invasive prenatal diagnosis of trisomy 13, i.e., pre-CVS, in the first trimester. The high number of fetal NRBCs detected indicates a connection with aneuploidy, probably due to early impairment of the feto-maternal barrier.     

Peripheral O2 diffusion does not affect V(O2)on-kinetics in isolated insitu canine muscle

To test the hypothesis that muscle O2 uptake (V(O2)) on-kinetics is limited, at least in part, by peripheral O2 diffusion, we determined the V(O2) on-kinetics in 1) normoxia (Control); 2) hyperoxic gas breathing (Hyperoxia); and 3) hyperoxia and the administration of a drug (RSR-13, Allos Therapeutics), which right-shifts the Hb-O2 dissociation curve (Hyperoxia+RSR-13). The study was conducted in isolated canine gastrocnemius muscles (n = 5) during transitions from rest to 3 min of electrically stimulated isometric tetanic contractions (200-ms trains, 50 Hz; 1 contraction/2 s; 60-70% peak V(O2)). In all conditions, before and during contractions, muscle was pump perfused with constantly elevated blood flow (Q), at a level measured at steady state during contractions in preliminary trials with spontaneous Q x Adenosine was infused intra-arterially to prevent inordinate pressure increases with the elevated Q x Q was measured continuously, arterial and popliteal venous O2 concentrations were determined at rest and at 5- to 7-s intervals during contractions, and V(O2) was calculated as Q x arteriovenous O2 content difference. PO2 at 50% HbO2 saturation (P50) was calculated. Mean capillary PO2 (Pc(O2)) was estimated by numerical integration. P50 was higher in Hyperoxia+RSR-13 [40 +/- 1 (SE) Torr] than in Control and in Hyperoxia (31 +/- 1 Torr). After 15 s of contractions, Pc(O2) was higher in Hyperoxia (97 +/- 9 Torr) vs. Control (53 +/- 3 Torr) and in Hyperoxia+RSR-13 (197 +/- 39 Torr) vs. Hyperoxia. The time to reach 63% of the difference between baseline and steady-state V(O2) during contractions was 24.7 +/- 2.7 s in Control, 26.3 +/- 0.8 s in Hyperoxia, and 24.7 +/- 1.1 s in Hyperoxia+RSR-13 (not significant). Enhancement of peripheral O2 diffusion (obtained by increased PcO2 at constant O2 delivery) during the rest-to-contraction (60-70% of peak V(O2)) transition did not affect muscle V(O2) on- kinetics.     

Psychosocial characteristics of pregnant and nonpregnant HIV-seropositive women

Thirty-three HIV-positive women, 12 of whom were pregnant, participated in semistructured interviews to define areas of psychosocial need. Eighty-eight percent of the subjects reported current unemployment. A history of substance abuse was reported by 82 percent, suicide attempts by 52 percent, and sexual problems by 43 percent. Approximately 30 percent reported elevated levels of depressive symptoms on standardized symptom inventories. The pregnant women appeared psychologically healthier than the nonpregnant group. HIV-positive women face multiple psychosocial stressors and may experience significant psychological distress.     

Discovery of a novel tetrahydroacridine acetylcholinesterase inhibitor through an indexed combinatorial library

BACKGROUND: Methods for the rapid and efficient preparation of drug candidates through combinatorial chemistry are of increasing interest. We have previously reported an indexed combinatorial library method that allows both the preparation and testing of compounds in solution. We set out to apply this method to develop more effective analogs of the known, marketed drug tacrine, an acetylcholinesterase inhibitor. RESULTS: A one-step condensation of cyclohexanones with cyanoanilines to generate tetrahydroacridine pools was developed. The resulting library of (formally) 72 tetrahydroacridines was screened against acetylcholinesterase, and a compound 10-fold more potent than tacrine, 7-nitrotacrine, was discovered. Its increased potency could be readily explained by examining the known structure of the complex of acetylcholinesterase with tetrahydroacridine. CONCLUSIONS: In this work, we have provided a relatively rare example of carbon-carbon bond formation in a pool synthesis and have discovered a potentially useful acetylcholinesterase inhibitor.     

Influence of PS‐b‐PEO diblock copolymers on the compatibility of syndiotactic polystyrene modified epoxy blends

Homogeneous solutions of syndiotactic polystyrene (sPS) in diglycidylether of bisphenol A (DGEBA), containing 2.5, 5 and 7.5 wt % of thermoplastic with or without 0.5 and 1 wt % of poly(styrene‐b‐ethylene oxide) (PS‐b‐PEO) block copolymer, were polymerized using a stoichiometric amount of an aromatic amine hardener, 4,4′‐methylene bis (3‐chloro‐2,6‐diethylaniline) (MCDEA). The dynamic‐mechanical properties and morphological changes of sPS‐(DGEBA/MCDEA) compatibilized with different amount of PS‐b‐PEO have been investigated in this paper. The addition of the block copolymer produced significant changes in the morphologies generated. The size of the dispersed spherical sPS spherulites does not change significantly, but less spherulites of sPS appeared upon network formation in the systems with compatibilizer, what means that addition of compatibilizer in this system delayed crystallization of sPS in sPS‐(DGEBA/MCDEA) systems and change phase separation mechanism from crystallization‐induced phase separation (CIPS) and reaction‐induced phase separation (RIPS) almost only to RIPS. Moreover, PS‐b‐PEO with higher molecular weight of PS block seems to be a more effective compatibilizer than one with lower molecular weight of PS block. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 479–488, 2006     

Event-driven,pattern-based methodology for cost-effective development of standardized personal health devices

Experiences applying standards in personal health devices (PHDs) show an inherent trade-off between interoperability and costs (in terms of processing load and development time). Therefore, reducing hardware and software costs as well as time-to-market is crucial for standards adoption. The ISO/IEEE11073 PHD family of standards (also referred to as X73PHD) provides interoperable communication between PHDs and aggregators. Nevertheless, the responsibility of achieving inexpensive implementations of X73PHD in limited resource microcontrollers falls directly on the developer. Hence, the authors previously presented a methodology based on patterns to implement X73-compliant PHDs into devices with low-voltage low-power constraints. That version was based on multitasking, which required additional features and resources. This paper therefore presents an event-driven evolution of the patterns-based methodology for cost-effective development of standardized PHDs. The results of comparing between the two versions showed that the mean values of decrease in memory consumption and cycles of latency are 11.59% and 45.95%, respectively. In addition, several enhancements in terms of cost-effectiveness and development time can be derived from the new version of the methodology. Therefore, the new approach could help in producing cost-effective X73-compliant PHDs, which in turn could foster the adoption of standards.     

Porous poly(2-hydroxyethyl acrylate) hydrogels prepared by radical polymerisation with methanol as diluent

Dynamic-mechanical and water sorption properties of porous and non-porous hydrogels have been studied as a function of their porosity and crosslinking density. Porous hydrogels with different crosslinking densities were prepared by co-polymerisation of 2-hydroxyethyl acrylate and ethyleneglycol dimethacrylate in solution in methanol. Pores were formed due to the segregation of the solvent from the polymer network during the polymerisation process. The porosity of the samples was observed by scanning electron microscopy. The pores collapse during the drying process after polymerisation but they reopen when the xerogel is immersed in liquid water. Bulk polymer networks with varying crosslinking densities were also synthesised and used as a reference in the analysis of the porous hydrogels. Water sorption from the gas phase and from the liquid phase was studied by means of equilibrium sorption isotherms and immersion experiments, respectively. Dynamic-mechanical spectroscopy conducted on the xerogels shows that the elastic modulus in the rubber-like state highly depends on the amount of solvent used in the polymerisation what is attributed to the presence of discontinuity surfaces in the xerogel although the pores are closed.