Impaired helix 12 dynamics due to proline 892 substitutions in the androgen receptor are associated with complete androgen insensitivity

Human Molecular Genetics (2006) 15, 921–931;     

Reflex Cardiorespiratory Effects of Nociceptive Oesophageal Distension in the Decerebrate Rat

It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible pressor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker alpha-bungarotoxin (140 microg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs.     

Attentional demands of continuously monitoring orientation using vestibular information.

The aim of this series of experiments was to determine whether attention is normally required for continuously processing vestibular information concerning orientation, or is required only when orientation is disrupted (eg by vestibular dysfunction or by conflicting visual and vestibular orientation cues). In the first two studies, healthy subjects were passively oscillated, and indicated when they perceived they were passing through their starting position. There was only weak evidence for interference between performance on this 'continuous orientation monitoring task' and on concurrent mental tasks. However, a third study showed that when patients with vestibular imbalance carried out the continuous orientation monitoring task their performance on a concurrent mental arithmetic task was substantially impaired. This dual task interference was correlated with inaccuracy in judging orientation on the continuous orientation monitoring task, which in turn correlated with severity of recent vestibular symptomatology (assessed by questionnaire). In a fourth experiment, disorientation was induced in healthy subjects by rotating the visual field about the line of sight. Bidirectional interference was observed between monitoring orientation (assessed by accuracy in setting a rod to the perceived vertical) and performance of an arithmetic task. Dual task interference was correlated with baseline levels of disorientation induced by the visual field, as indicated by inaccuracy in judging the visual vertical. These findings suggest that monitoring orientation makes significant demands upon cortical processing resources when disorientation is induced, whether the disorientation results from deficient sensory functioning or from ambiguous perceptual information.     

Ischemic rat brain extracts induce human marrow stromal cell growth factor production

Intravenous administration of human bone marrow stromal cells (hMSCs) after middle cerebral artery occlusion (MCAo) in rats provides functional benefit. We tested the hypothesis that these functional benefits are derived in part from hMSC production of growth and trophic factors. Quantitative sandwich enzyme‐linked immunosorbent assay (ELISA) of hMSCs cultured with normal and MCAo brain extracts were performed. hMSCs cultured in supernatant derived from ischemic brain extracts increased production of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). These neurotrophins and angiogenic growth factors increased in a post‐ischemia time‐dependent manner. The hMSC capacity to increase expression of growth and trophic factors may be the key to the benefit provided by transplanted hMSCs in the ischemic brain.     

Physician evaluation after medical errors: does having a computer decision aid help or hurt in hindsight?

OBJECTIVE: The authors examined whether physicians' use of computerized decision aids affects patient satisfaction and/or blame for medical outcomes. METHOD: Experiment 1: Fifty-nine undergraduates read about a doctor who made either a correct or incorrect diagnosis and either used a decision aid or did not. All rated the quality of the doctor's decision and the likelihood of recommending the doctor. Those receiving a negative outcome also rated negligence and likelihood of suing. Experiment 2: One hundred sixty-six medical students and 154 undergraduates read negative-outcome scenarios in which a doctor either agreed with the aid, heeded the aid against his own opinion, defied the aid in favor of his own opinion, or did not use a decision aid. Subjects rated doctor fault and competence and the appropriateness of using decision aids in medicine. Medical students made judgments for themselves and for a layperson. RESULTS: Experiment 1: Using a decision aid caused a positive outcome to be rated less positively and a negative outcome to be rated less negatively. Experiment 2: Agreeing with or heeding the aid was associated with reduced fault, whereas defying the aid was associated with roughly the same fault as not using one at all. Medical students were less harsh than undergraduates but accurately predicted undergraduate's responses. CONCLUSION: Agreeing with or heeding a decision aid, but not defying it, may reduce liability after an error. However, using an aid may reduce favorability after a positive outcome.     

Xenograft rejection--all that glitters is not Gal.

Xenotransplantation is being developed in the hope of resolvingthe critical shortage of donor organs for transplantation. TheEurotransplant waiting lists [1] for donor organs of variouskinds number almost 16 000 patients and the US lists [2] morethan 90 000 patients. Renal transplantation, for instance, cost-effectivelyconfers a significant survival advantage [3] and improvementof quality of life [4]. But whereas currently, in Europe, nearly12 000 end-stage renal disease patients await a suitable donor,only 3383 kidney transplants were performed in 2005, with anaverage waiting time of 1174 days [1]. Substantial researchefforts are being made in the field of xenotransplantation,and the immunological barriers are gradually being elucidated.Pig-to-human xenogeneic