Oral hypoglycemic agents. Pyrimido[1,2-a]indoles and related compounds.

A series of pyrimido[1,2-a]indoles were synthesized and studied for their hypoglycemic activity following oral administration at a standard dose of 100 mg/kg to fed rats. The effect of 10-alkoxyalkyl, 10-alkyl, 10-aryl, and 3,3-dialkyl substitution on the activity of 10-hydroxypyrimido[1,2-a]indoles was investigated. Relative potencies of a number of the most active compounds were defined by three-point dose-response studies. The most potent compounds were those with either 3,3-dimethyl substituents, compounds 21, 22, and 38, or 3,3-spirocyclohexane substituents, compounds 39 and 49. 10-Aminopyrimido[1,2-a]indoles were in general less active than the 10-hydroxy analogues, and potency was further decreased by derivatizing the 10-amino group. The most potent 10-amino derivatives were 57 and 58.     

Substance P augments the rate of vasodilation induced by calcitonin gene-related peptide in porcine ophthalmic artery in vitro.

Peptides may function as neurotransmitters liberated antidromically by sensory nerve fibres, provoking vascular responses having potential importance in some neurological disorders. Dose-response relaxation curves induced by substance P (SP) and calcitonin gene related peptide (CGRP) have been studied in porcine ophthalmic arteries in vitro. Both peptides induced vasodilation when tested separately (CGRP much greater than SP). Because of the putative interactions between such peptides in this vascular territory, a computerised system was also used for analysing over time the response to a single addition of either 10(-8) M CGRP, 10(-8) M SP or a combination of 10(-8) M SP + 10(-8) M CGRP. SP did not augment the maximum relaxation induced by CGRP alone, but increased significantly the rate of relaxation during the initial phase of the response. The effect induced by the SP+CGRP combination was stronger than the sum of the individual SP and CGRP-induced relaxations during the first 4 min of the response, which suggests a SP-CGRP synergism in this artery.     

Decreased activity of rat A10 dopamine neurons following withdrawal from repeated cocaine.

Electrophysiological techniques were used to determine the basal activity of A10 dopamine (DA) neurons in the rat ventral tegmental area after a 10-14 day withdrawal from repeated cocaine treatment (10.0 mg/kg i.p. twice daily for 14 days). The number of spontaneously active A10 DA cells was significantly decreased (42%) in the cocaine-treated rats. This decreased activity may underlie the diminished basal levels of synaptic DA within the nucleus accumbens previously reported in cocaine-withdrawn rats and may account for anhedonia, anergia and cocaine craving reported by withdrawn cocaine addicts.     

Prediction of general practice workload from census based social deprivation scores.

STUDY OBJECTIVE--The aim was to compare the ability of census based social deprivation scores devised by Jarman, Carstairs, and Townsend to predict workload in general practice. DESIGN--This was a prospective study of 140,050 patients registered with general practices over one year from 1 July 1981 (Third National Morbidity Survey). Main outcome measures were workload score for each patient, defined as a weighted sum of consultations at the surgery and consultations elsewhere, excluding preventive procedures. SETTING--25 general practices in England and Wales. MAIN RESULTS--In multivariate analyses the Jarman, Carstairs, and Townsend indices all predicted workload, but the Townsend index was the best predictor, with both housing tenure and car ownership being strong predictors of workload. The overcrowding and geographical mobility variables used in the Jarman index did not predict increased workload. The weighting assigned to children under five by the Jarman index underestimated the additional workload this group generated. CONCLUSIONS--For identifying social pressures on general practice workload the Jarman index is less valid than other census based scores because it fails to include car ownership and housing tenure. A more rational scheme for compensating general practitioners would directly weight the capitation fee for children aged under five years and allocate current deprivation payments according to the Townsend index or a similar score. This would redistribute resources from London to deprived areas in northern England.     

Improved power control during microwave heating in biological applications.

The heating performance of prototype variable power control units attached to two domestic microwave ovens, 500 W and 700 W, was investigated. The units employed the phase control method where rated voltage was obtained by switching AC supply at a particular angular position on the sinusoidal voltage. In order to create experimental conditions employed in a previous study, Sydney tap water (50 mL) was heated at a 10% power level in the 500 W oven. Water boiled at 10 min in both experiments. However, the precision and control of the heating was greatly improved with addition of the control unit. A disinfecting solution (50 mL) and a tissue fixative (10 mL) were included for experiments with the 700 W oven. A power level of only 1% was sufficient to maintain the temperature of the fixative at low temperatures (30-40 degrees C) where many biological reactions occur. The present results indicate that microwave heating power can be controlled by the variable power control method. This will make temperature control possible through the provision of an electronic feedback loop which links a thermocouple with the power control unit.     

Music therapy: an intervention to reduce anxiety in the myocardial infarction patient.

The purpose of this study was to examine the effects of relaxing music on elevated state anxiety in patients with a confirmed medical diagnosis of acute myocardial infarction. In addition, the relationship between trait anxiety and state anxiety was analyzed. A purposive sample of 40 myocardial infarction patients was randomly assigned to an experimental or control group. Statistically significant reduction in heart rate, respiratory rate, and state anxiety scores were found in the group that listened to relaxing music. A statistically significant positive correlation was found between trait anxiety scores and baseline state anxiety scores. Statistically significant negative correlations were found between trait anxiety scores and the degree of change in posttreatment state anxiety scores when examined as a net change, as well as a percent change. Results suggested that music therapy may be an effective intervention to reduce state anxiety levels in the acute myocardial infarction patient.     

乳酸脱氢酶实验检测细胞新陈代谢的实验研究

目的 探索LDH实验检测细胞活力的可行性。方法 原代培养骨髓细胞和软骨细胞，用LDH实验测定上述两组细胞的活力，并与镜下活体观察到细胞的生长状况相比较。与目前比较成熟的测定细胞活力的MTS实验的测得的值相比较。结果 LDH实验对上述两组细胞的活力的测定结果与镜下活体观察到的结果相符合。与MTS实验的测得的结果经统计学处理无显著差异。结论 LDH实验可用于细胞活力的直接测定，而对活细胞的生存、繁殖无影响。     

Cluster headache: phospholipid metabolism in polymorphonuclear cells

Our group has previously reported significant changes in the incorporation of precursors into glycerophospholipids, particularly phosphatidylserine, in polymorphonuclear cells obtained from the peripheral blood of cluster headache patients, when compared with controls. The potential of these results led to further work using both the previous methodology and a modified isolation technique to obtain polymorphonuclear cells in as pure a state as possible. Neither the new results obtained using the original technique, nor the results with high purity polymorphonuclear cells from controls and cluster headache patients, confirm the marked changes in precursor uptake into glycerophospholipids originally reported.     

Identifying incident cases of parkinsonism among veterans using a tertiary medical center.

To better understand the impact of incident Parkinson's disease (PD) on the Veteran's Health Administration (VHA) and to develop methods applicable to future epidemiological research, we performed a medical record review study at a tertiary referral VHA medical center. Searching the local data base, we identified 782 veterans with diagnostic codes for PD or secondary parkinsonism (SP) between 1998 and 2000. Based on structured medical record review, a movement disorders specialist confirmed diagnoses for incident parkinsonism cases. Among the 782, 191 incident parkinsonism cases were identified (100 PD, 75 SP, and 16 Parkinson's Plus). Incident PD cases were older at diagnosis (74.5 vs. 70.4 yr; P < 0.05) and more likely to be white (81% vs. 62; P < 0.07) than incident SP cases. Diagnostic codes were insufficient to distinguish between incident PD and SP (positive predictive value, 57% and 39%, respectively), and VHA sources failed to identify 21% of confirmed deaths among the incident PD cohort by November 2004. Although the large number of incident cases identified suggests PD is an important cause of disability among elderly VHA users, observed limitations of VHA sources for identifying incident PD cases and determining their vital status should be considered when designing future studies.