Estimation of the biophase concentration of noradrenaline at presynaptic α2-adrenoceptors in brain slices

Summary The aim of the present study was to determine the local concentrations of noradrenaline existing at presynaptic ₂-adrenoceptors during electrical pulse train stimulation of brain slices at different frequencies. The experiments are based on the assumption that the concentration of released noradrenaline at the ₂-adrenoceptors exerting a certain autoinhibition should be equal to the concentration of exogenous noradrenaline causing the same inhibition under conditions in which any influence of the released transmitter is excluded. In order to avoid autoinhibition, hippocampus and cortex slices of the rabbit and the rat, prelabelled with [³H]noradrenaline and superfused in presence of an uptake inhibitor, were electrically stimulated using 4 pulses delivered at 100 Hz (POP stimulation). Exogenous noradrenaline diminished the overflow of tritium elicited by POP stimulation in a concentration-dependent manner. In rabbit brain tissues the EC₅₀ value and maximum inhibition of noradrenaline release were found to be approximately 6 nmol/l and more than 95%, respectively, whereas in rat tissues the corresponding values were between 20 and 30 nmol/l and approximately 90%. When electrical stimulation was performed with trains of 36 pulses delivered at 0.1, 0.3 or 3 Hz in absence or presence of an uptake inhibitor, the ₂-adrenoceptor antagonist yohimbine (1 or 10 mol/l) enhanced the evoked tritium overflow in a manner which was dependent on the frequency of stimulation and on blockade of the re-uptake mechanism. The facilitatory effects of yohimbine reflected an extent of autoinhibition which was between 53% (36 pulses/0.1 Hz, no uptake inhibitor) and 85% (36 pulses/3 Hz, uptake inhibitor present) in rabbit and between 16% (36 pulses/0.3 Hz, no uptake inhibitor) and 71% (36 pulses/3 Hz, uptake inhibitor present) in rat brain slices. Accordingly, the corresponding estimated biophase concentrations of noradrenaline were generally higher in rat than in rabbit tissues (they were between 32.5 and 74.5 or 5.1 and 51.6 nmol/l in the presence or absence of an uptake inhibitor, respectively, in the rat, and between 15 and 23.1 or 6.1 and 18.6 nmol/l in the rabbit). The observed frequency dependence of the effect of re-uptake blockade on the calculated biophase concentrations of noradrenaline would be compatible with the idea of a dependence of the effectiveness of the re-uptake mechanism on the firing rate of the neurone in being more effective at lower frequencies. Moreover, the stikingly low biophase concentrations of noradrenaline suggest that also in brain tissue noradrenaline causes lateral inhibition of release as has recently been shown for guinea-pig vas deferens. Send offprint requests to C. Allgaier at the above address     

Stiffness, compliance, elasticity and force generation of outer hair cells.

Isolated outer hair cells (OHCs) were partially sucked into especially designed cell capillaries allowing an experimental reconstitution of the cells' electroanatomy. The experimental approach separated the apical from the basolateral parts of the cells thus forming an artificial scala media and scala tympani. Resistance between both was 121 +/- 42 M omega. A sequence of negative and positive pressures was applied to the basal cell pole allowing "pulling" or "pushing" of the sensory cell investigated. The resulting length changes together with the known pressures allowed the estimation of an actual longitudinal compliance of 354 +/- 35 m/N. Following "pulling" OHCs tended to resume their initial shape after the force had ceased to be effective indicating elastic distortions. The calculated elasticity modulus of OHCs amounted to 6.1 +/- 3.4 kN/m2. From this data an actual longitudinal whole cell stiffness of OHCs of 3 x 10(-3) N/m was calculated. Ultrasound scanning of immobilized OHCs identified the cuticular plate (CP) and a central core between CP and basal cell pole as structures contributing to the cells' acoustic stiffness. Changes of the potential differences between the artificial scala media and scala tympani resulted in active length changes following the command voltage with a slope of delta 1/(1 x U) = 0.055 V-1. Assuming the validity of Hooke's law, the force generation associated with the active length changes can be calculated since the compliance is known.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship of blood pressure to a brief measure of anger during routine health screening

A brief questionnaire (12 items) was developed to assess aspects of anger that could be expeditiously obtained during health screenings where medical students and residents can acquire valuable research and clinical experience simultaneously. Blood pressures were measured immediately upon sitting and after 3 minutes in 179 subjects who attended a health fair in Nashville. The questionnaire was administered after both blood pressure measurements were acquired. Scores on the measure of anger correlated significantly (P = .0009) with resting systolic blood pressure (SBP) in both blacks and whites while a measure of "John Henryism" showed no correlation with blood pressure in either group (P = .81). The findings are consistent with the literature in supporting a connection between anger and blood pressure but do not support the relationship between John Henryism and blood pressure.     

Child psychiatrists' views of DSM-III-R: a survey of usage and opinions

The DSM-IV Child Psychiatry Work Group surveyed 460 child psychiatrists about their use of DSM-III-R and their reactions to specific proposed nosological revisions for DSM-IV. This paper presents the responses of the sample as a whole and of respondent subgroups with different theoretical, practice, and training characteristics. The survey indicates that DSM-III and DSM-III-R are widely used and generally accepted by child psychiatrists. Ninety-eight percent of respondents believe a criterion-based diagnostic system is useful, and 65% consider DSM-III-R to be an improvement over DSM-III. Depending on the diagnosis 47% to 66% of the respondents reported that they generally assess all applicable criteria and 28% to 49% often refer to the manual before assigning a diagnosis. A majority of respondents supported proposals for several new diagnostic subtypes. Ninety-three percent of respondents indicated that "adequacy of family support" was very valuable for treatment planning or estimating prognosis. Fifty-five percent of respondents admitted to diagnosing adjustment disorders in order to avoid the stigma associated with other disorders. Child psychiatrists who are psychodynamically oriented or practicing in an office-based setting or out of training for more than 10 years tend to use the DSM-III-R less rigorously.     

Nd-YAG laser ablation of arteriosclerotic obstructions: Clinical long-term results in femoropopliteal artery occlusions

Laser recanalization of peripheral artery occlusions was performed in 338 patients. A continuous wave Nd-YAG laser was used in combination with sapphire-probe laser catheters. The initial recanalization rate was 85%. Complications such as dissections, perforations, emboli and spasm were observed in 14%. The cumulative patency rate after 3 years was 48%.     

Validating a New Non-penetrating Sham Acupuncture Device：Two Randomised Controlled Trials

IntroductionIn clinical trials of the efficacy of manualtreatm ents like surgery or acupuncture,control groups are comm only given‘sham’procedures.Sham procedures,inorder to be true placebos,must be 1) in-distinguishable from the real treatm entand 2 ) inactive.In acupuncture trials,various controls for the process of insert-ing a needle and stimulating it have beenused.These include needling off point orat inappropriate points[1 ,2 ] ,pricking orscratching with blunt needle[3,4 ] ,needlingw…     

Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain.

PURPOSE: To compare the incidence of palliative response in patients with hormone-resistant prostate cancer (HRPC) treated with mitoxantrone and prednisone (MP) plus clodronate with that of patients treated with MP plus placebo. MATERIALS AND METHODS: Men with HRPC, bone metastases, and bone pain were randomly assigned to receive clodronate 1,500 mg administered intravenously (IV) or placebo every 3 weeks, in combination with mitoxantrone 12 mg/m2 IV every 3 weeks and prednisone 5 mg orally bid. Patients completed the present pain intensity (PPI) index and Prostate Cancer-Specific Quality-of-Life Instrument at each treatment visit and used a diary to record analgesic use on a daily basis. The primary end point was a reduction to zero or of two points in the PPI or a decrease of 50% in analgesic intake, without increase in either. RESULTS: The study accrued 209 eligible patients over 44 months. One hundred sixty patients (77%) had mild PPI scores (1 or 2), and 49 (24%) had moderate PPI scores (3 or 4). The primary end point of palliative response was achieved in 46 (46%) of 104 patients on the clodronate arm and in 41 (39%) of 105 patients on the placebo arm (P =.54). The median duration of response, symptomatic disease progression-free survival, overall survival, and overall quality of life were similar between the arms. Subgroup analysis suggested possible benefit in patients with more severe pain. CONCLUSION: MP provides useful palliation in symptomatic men with HRPC. Clodronate does not increase the rate of palliative response or overall quality of life. Clodronate may be beneficial to patients who have moderate pain, but this requires further confirmation.     

Screening for complement deficiency in bacterial meningitis

Seventy-seven children with bacterial meningitis were screened for complement deficiency. Both the classical and the alternate pathways were normal in 75 patients. Transiently reduced total haemolytic activity of the classical pathway was documented in a boy with meningococcal meningitis. Total haemolytic activity of both the classical and the alternate pathways were reduced in another patient with pneumococcal meningitis: individual complement components determination indicated predominant activation of the alternate pathway.     

Foix-Chavany-Marie (anterior operculum) syndrome in childhood: a reappraisal of Worster-Drought syndrome

Foix-Chavany-Marie syndrome (FCMS) is a distinct clinical picture of suprabulbar (pseudobulbar) palsy due to bilateral anterior opercular lesions. Symptoms include anarthria/severe dysarthria and loss of voluntary muscular functions of the face and tongue, and problems with mastication and swallowing with preservation of reflex and autonomic functions. FCMS may be congenital or acquired as well as persistent or intermittent. The aetiology is heterogeneous; vascular events in adulthood, nearly exclusively affecting adults who experience multiple subsequent strokes; CNS infections; bilateral dysgenesis of the perisylvian region; and epileptic disorders. Of the six cases reported here, three children had FCMS as the result of meningoencephalitis, two children had FCMS due to a congenital bilateral perisylvian syndrome, and one child had intermittent FCMS due to an atypical benign partial epilepsy with partial status epilepticus. The congenital dysgenetic type of FCMS and its functional epileptogenic variant share clinical and EEG features suggesting a common pathogenesis. Consequently, an increased vulnerability of the perisylvian region to adverse events in utero is discussed. In honour of Worster-Drought, who described the clinical entity in children 40 years ago, the term Worster-Drought syndrome is proposed for this unique disorder in children.     

英国补充治疗的成本效果：系统性综述

补充治疗（包括针灸和草药——编者注）是否应该整合纳入英国国民医疗卫生服务体系（NHS），成本效益的数据资料成为争论的关键问题。但是，就我们所知，以前没有人对英国补充疗法的成本效益做过研究。