Anaesthetic agents decrease the activity of nitric oxide synthase from human polymorphonuclear leucocytes

Nitric oxide (NO) inhibitors reduce the threshold for anaesthesia. We have investigated the action of anaesthetic agents on human nitric oxide synthase (NOS) activity. Thiopentone reduced mean NOS activity to 36.6 (SD 8.9) % of control at 100 mumol litre-1 (P < 0.001) and 50.9 (20.3) % at 1 mmol litre-1 (P < 0.05). Ketamine showed similar effects, with activity reduced to 67.0 (17.6) % (P < 0.05) and 57.7 (8.5) % (P < 0.001) at 100 mumol litre-1 and 1 mmol litre-1, respectively. Etomidate 100 mumol litre-1 did not significantly alter activity (88.2 (8.1) %) but 1 mmol litre-1 did (60.6 (10.4) %, P < 0.005). Halothane also caused a significant decrease in NOS activity at all concentrations. This effect was specific as other enzymes were unaffected. We conclude that anaesthetic agents have a profound effect on NOS activity and as inhibition of NO release augments anaesthesia, we suggest that this may play a role in the mechanism of anaesthesia in humans.      

Nine Years of the Freebase Cocaine Epidemic in the Bahamas

Nine years after the beginning of the epidemic of freebase (crack) cocaine abuse in the Bahamas, this historical study was done to characterize the natural course of the epidemic and to estimate the effectiveness of control measures. The authors' data include the incidence of new cases at the only psychiatric hospital in the Bahamas and at the primary community psychiatric clinic in the nation. The Bahamian response included 1) demand reduction, 2) supply reduction, and 3) reduction of money laundering. The annual number of new cases of crack abuse presenting for treatment declined from 1987 to mid-1991 in both facilities, but in 1992 it began rising again in the inpatient setting only. The changes in recent years have been accompanied by an increase in violent crimes against persons, especially robberies. (American Journal on Addictions 1994; 3:14–24)     

Development of the vestibular and auditory system of the northern native cat,Dasyurus hallucatus

The developing vestibular and auditory system of the native cat Dasyurus hallucatus was examined from birth to day 55 postpartum to determine when the six sensory regions had an adult structure. The utricle, a sensory epithelium with an overlying discrete population of otoliths, was present in the newborn native cat. The saccule, which has a similar structure to the utricle, and the three crista ampullaris of the semicircular canals, were present by day 21 postpartum. The organ of Corti was formed by day 50 and the external ear duct was patent by day 55 postpartum. Hair is first seen on the native cat by day 45 when the young first leave the pouch. They are left in the nest and travel on the back of the lactating mother until about day 80. The eyes open on approximately day 75. Thus, the native cat has fully functional visual, auditory, and vestibular systems when the juvenile leaves the nest. © 1992 Wiley-Liss, Inc.     

The effects of three nebulized osmotic agents in the dry larynx.

PURPOSE: This investigation examined the effects of nebulized hypertonic saline, isotonic saline (IS), and sterile (hypotonic) water on phonation threshold pressure (PTP) and self-perceived phonatory effort (PPE) following a surface laryngeal dehydration challenge. METHOD: In a double-blind, randomized experimental trial, 60 vocally healthy women (n = 15 per group) underwent a laryngeal desiccation challenge involving oral breathing for 15 min using medical-grade dry air (RH<1%). Three of the four groups then received nebulized isotonic saline (0.9% NaCl), hypertonic saline (7% NaCl), or sterile (hypotonic) water, respectively; the 4th group served as a nontreatment control. PTP and PPE were estimated for high-pitched productions at baseline, immediately postdesiccation, and at 5, 20, 35, and 50 min postnebulization. RESULTS: PTP increased significantly for all groups following the desiccation challenge. PTP values were, on average, 0.5 cm H(2)O greater immediately postdesiccation versus baseline. In contrast, PTP values did not change significantly following the administration of nebulized treatments, although a temporary trend toward a reduction in PTP was observed for the IS group. Unexpectedly, PPE ratings decreased significantly after the desiccation challenge. In general, PPE ratings were poorly correlated with PTP measures. CONCLUSION: A laryngeal desiccation challenge (i.e., temporary exposure to extremely low relative humidity while breathing transorally) significantly increased PTP. Although interesting trends emerged, none of the nebulized treatments significantly enhanced recovery from the negative effects of desiccation on PTP. In light of very low correlations between PTP and PPE, serious questions are raised regarding presumed associations between these measures.     

The peroxisome proliferator-activated receptor gamma coactivator-1 alpha gene (PGC-1alpha) is not associated with type 2 diabetes mellitus or body mass index among Hispanic and non Hispanic Whites from Colorado.

The objective of the study was to test for an association between type 2 diabetes mellitus (T2DM) and body mass index (BMI) and three single nucleotide polymorphisms (SNP)s in the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) gene. We were also interested in whether these associations differed by tertiles of diet, physical activity or presence of polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene among Hispanics and Non-Hispanic Whites (NHW) from Colorado. We studied 216 Hispanic pedigrees (1850 nuclear families) and 236 NHW pedigrees (1240 families) from the San Luis Valley and Denver. We genotyped the Gly482Ser, Thr528Thr and Thr612Met polymorphisms in the PGC-1alpha gene and the Pro12Ala polymorphism of the PPAR-gamma gene. Historical physical activity (average METS/week) as well as average dietary intake over the past year was assessed by self-report. Data were analyzed using the Family Based Association Test (FBAT) as well as generalized estimating equations (GEE). We did not find any significant association between three SNPs in the PGC-1alpha gene and T2DM in Hispanics or NHW; however, using FBAT, we found the common Thr612Thr allele of the PGC-1alpha gene to be associated with T2DM among Hispanic subjects carrying the rare Pro12Ala allele of the PPAR-gamma gene (p=.003). We found similar associations when we considered a haplotype containing that allele (p=.002). However, the results of the GEE analysis did not confirm these findings: odds ratio (OR)=1.68, 95% CI (0.5, 5.2) suggesting these results may due to chance. BMI also did not show any consistent associations with the PGC-1alpha gene. In conclusion, we did not find an association between the PGC-1alpha gene and T2DM or BMI and there were no consistent interactions with diet, physical activity or the Pro12Ala polymorphism of the PPAR-gamma gene.     

Noninvasive measurement of systemic vascular resistance using Doppler echocardiography.

BACKGROUND: Systemic vascular resistance (SVR) is an integral therapeutic component of patients with heart failure and shock. We hypothesized that the ratio of the peak mitral regurgitant velocity (MRV) (m/s) to left ventricular outflow time-velocity integral (TVI(LVOT)) (cm) by Doppler would provide a noninvasive correlate of SVR. METHODS: SVR was correlated to MRV/TVI(LVOT) in 33 patients undergoing right heart catheterization. Receiver operating characteristic curves were generated to determine the best-balanced sensitivity and specificity to identify SVR > 14 Wood units (WU) and <10 WU. RESULTS: MRV/TVI(LVOT) correlated well with SVR (r = 0.842, 95% confidence interval 0.7-0.92, P <.001, Y = 0.459 + 49.397*X). By receiver operating characteristics, MRV/TVI(LVOT) > 0.27 had a 70% sensitivity and a 77% specificity to identify SVR > 14 WU. MRV/TVI(LVOT) < 0.2 had a 92% sensitivity and a 88% specificity to identify SVR < 10 WU. CONCLUSION: Doppler echocardiography provides a reliable noninvasive assessment of SVR.