Divergent effects of ACE-inhibition and calcium channel blockade on NO-activity in systemic and renal circulation in essential hypertension

OBJECTIVE: Nitric oxide is a vasodilating and blood pressure lowering substance. To investigate whether calcium antagonists or angiotensin-converting enzyme (ACE) inhibitors increase vascular nitric oxide activity, we assessed systemic and renal vascular sensitivity to nitric oxide synthase inhibition in hypertensives on and off medication. METHODS: Ten essential hypertensive patients, aged 22-51 years, were studied 3 times: > or = 4 weeks off medication, after 3 weeks treatment with enalapril 20 mg twice a day and after 3 weeks nifedipine 60 mg/day. Each time, 24-h blood pressure registration was performed, followed by a clearance study to obtain a 3-h dose-response curve for intravenously infused NG-monomethyl-L-arginine (L-NMMA, respectively 0.75, 1.5 and 3.0 mg/kg/h). RESULTS: L-NMMA dose-dependently increased mean arterial pressure with 5 +/- 2 mmHg and systemic vascular resistance with 24 +/- 5% at maximum dose, whereas cardiac output decreased (all P < 0.001). Enalapril and nifedipine treatment decreased blood pressure, while the L-NMMA-induced increase in systemic vascular resistance was potentiated (enalapril: 45 +/- 7% and nifedipine: 46 +/- 8%; both P < 0.01). L-NMMA also dose-dependently decreased renal blood flow by 58 +/- 8% at maximum dose (P < 0.001), but neither drug potentiated these effects. CONCLUSION: These results indicate that, in essential hypertensives, antihypertensive therapy with enalapril or nifedipine increases nitric oxide dependency of systemic vascular tone, which may play a role in the blood pressure lowering effect of these drugs. However, this phenomenon cannot be observed in the renal circulation, suggesting a different regulation of endothelium-dependent vasomotion in the hypertensive kidney.     

Fine-needle aspiration of the breast: cell counts as an illusion of adequacy. A clinical cytopathologist''s point of view

Pattern reversal visual evoked potentials (PVEPs) were recorded in 20 patients with migraine with aura (MA), 19 patients with migraine without headache (migraine equivalent; ME) during interictal periods, and 34 normal subjects. All migraine patients had hemianopsia or fortification spectra during attacks. In both MA and ME patients of less than 49 years of age, there were significant (p<0.01) differences in amplitude of PVEPs at the mid-occipital and contralateral to visual aura electrode sites compared to normal subjects. Amplitude of PVEPs in MA and ME showed significant (p<0.001) increases when recorded soon after attacks, especially within 10 days. There was a significant (p<0.01) correlation between percentage asymmetries and the duration of illness in both MA and ME. We conclude from our PVEP findings that cortical spreading depression remains the most likely explanation for the migraine visual aura.     

Alcohol consumption and utilization of health services in a health maintenance organization

OBJECTIVES: This study examined the relation between alcohol use and utilization of health services during a 3-year period in a sample of 4,264 adult respondents to a member health survey in a health maintenance organization. METHODS: Respondents were categorized as abstainers (no drinks in the past year, n = 1,139), lighter drinkers (less than seven drinks/week, n = 2,330), moderate drinkers (seven to 13 drinks/week, n = 498), and heavier drinkers (> or =14 drinks/week, n = 297). Each drinker group was compared with abstainers on outpatient visits, hospital days, and number of hospitalizations controlling for age, race, and health plan membership. RESULTS: The mean number of outpatient visits was inversely related to the amount of alcohol consumed. Significant differences also were found for mean number of hospitalizations and mean days hospitalized per year. Compared with the three drinker groups, abstainers were significantly higher on both inpatient measures. CONCLUSIONS: These results might be explained by the inclusion in the abstainer group of exdrinkers who quit because of illness, inattention to health problems by heavier drinkers, or lower rates of illness among drinkers. The findings underscore the importance of replicating our study in other cohorts in which problem drinkers can be identified and compared with non-problem drinkers and in which lifelong abstainers can be separated from exdrinkers in the analysis.     

Analogues of the potential antipsychotic agent 1192U90: amide modifications

BACKGROUND: The importance of evidence-based practice has stimulated interest in the methodology of clinical trials. Various weaknesses of evaluation research in the alcohol field have been indicated previously. This study set out to develop a comprehensive system for the assessment of the methodological quality of outcome research for treatment of alcohol misuse and to apply the system to well-known trials in the area. METHODOLOGY: A sample of the most highly cited controlled trials of interventions for alcohol misuse was selected using the Science Citation Index. Thirty methodological criteria were formulated and a scoring system devised. Two raters applied this system to the sample of trials. Reliability testing was performed and used to refine the criteria. RESULTS: Inter-rater reliability of the overall quality score was initially 0.85 and 0.92 after review and re-rating. Internal consistency was also high (0.87). Quality score correlated with year of publication. Certain areas of methodology were poorly addressed in the sample, including specification of main outcomes, documentation of recruitment and selection procedures, testing of blinding, analysis of withdrawals and reporting of results. DISCUSSION: The methodology of this sample of trials was frequently deficient in ways which might bias results or compromise generalizability. It is recommended that the system of quality assessment described here is used to evaluate existing research and to inform the design of future studies.     

Cochlear implant place psychophysics. 2. Comparison of forward masking and pitch estimation data

Results for forward masking and numerical estimation of pitch were compared in a group of 6 adult subjects implanted with cochlear prostheses manufactured by Cochlear Limited. Data were collected for bipolar + 1 stimulation in all subjects, and for stimulation in one other mode, either common ground or monopolar, for all subjects but one. The pitch data show various irregularities and in each case can be seen to be broadly consistent with the corresponding forward masking data. It is shown that a 'centre of gravity' of the forward masking distribution varies with masker electrode in a manner that is qualitatively very similar to the variation of pitch estimate. It is suggested that, while pitch estimation results are consistent with those from forward masking, the latter contain more detailed information that may be useful in understanding intersubject variations in speech comprehension.     

Evaluation of a new point-of-care test that measures PAF-mediated acceleration of coagulation in cardiac surgical patients

BACKGROUND: This study was designed to evaluate a new point-of-care test (HemoSTATUS) that assesses acceleration of kaolin-activated clotting time (ACT) by platelet activating factor (PAF) in patients undergoing cardiac surgery. Our specific objectives were to determine whether HemoSTATUS-derived measurements correlate with postoperative blood loss and identify patients at risk for excessive blood loss and to characterize the effect of desmopressin acetate (DDAVP) and/or platelet transfusion on these measurements. METHODS: Demographic, operative, blood loss and hematologic data were recorded in 150 patients. Two Hepcon instruments were used to analyze ACT values in the absence (channels 1 and 2: Ch1 and Ch2) and in the presence of increasing doses of PAF (1.25, 6.25, 12.5, and 150 nM) in channels 3-6 (Ch3-Ch6). Clot ratio (CR) values were calculated with the following formula for each respective PAF concentration: clot ratio = 1-(ACT/control ACT). These values also were expressed as percent of maximal (%M = clot ratio/0.51 x 100) using the mean CRCh6 (0.51) obtained in a reference population. RESULTS: When compared with baseline clot ratios before anesthetic induction, a marked reduction in clot ratios was observed in both Ch5 and Ch6 after protamine administration, despite average platelet counts greater than 100 K/microliter. There was a high degree of correlation between clot ratio values and postoperative blood loss (cumulative chest tube drainage in the first 4 postoperative hours) with higher concentrations of PAF: CRCh6 (r = -0.80), %M of CRCh6 (r = -0.82), CRCh5 (r = -0.70), and %M of CRCh5 (r = -0.85). A significant (P < 0.01) improvement in clot ratios was observed with time after arrival in the intensive care unit in both Ch5 and Ch6, particularly in patients receiving DDAVP and/or platelets. CONCLUSIONS: Activated clotting time-based clot ratio values correlate significantly with postoperative blood loss and detect recovery of PAF-accelerated coagulation after administration of DDAVP or platelet therapy. The HemoSTATUS assay may be useful in the identification of patients at risk for excessive blood loss and who could benefit from administration of DDAVP and/or platelet transfusion.     

Abscisic acid induces oscillations in guard-cell cytosolic free calcium that involve phosphoinositide-specific phospholipase C

Oscillations in cytosolic free Ca2+ concentration ([Ca2+]cyt) are an important component of Ca2+-based signal transduction pathways. This fact has led us to investigate whether oscillations in [Ca2+]cyt are involved in the response of stomatal guard cells to the plant hormone abscisic acid (ABA). We show that ABA induces oscillations in guard-cell [Ca2+]cyt. The pattern of the oscillations depended on the ABA concentration and correlated with the final stomatal aperture. We examined the mechanism by which ABA generates oscillations in guard-cell [Ca2+]cyt by using 1-(6-[17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl]aminohexyl)-1H-pyrrole-2,5-dione (U-73122), an inhibitor of phosphoinositide-specific phospholipase C (PI-PLC)-dependent processes in animals. U-73122 inhibited the hydrolysis of phosphatidylinositol 4,5-bisphosphate by a recombinant PI-PLC, isolated from a guard-cell-enriched cDNA library, in a dose-dependent manner. This result confirms that U-73122 is an inhibitor of plant PI-PLC activity. U-73122 inhibited both ABA-induced oscillations in [Ca2+]cyt and stomatal closure. In contrast, U-73122 did not inhibit external Ca2+-induced oscillations in guard-cell [Ca2+]cyt and stomatal closure. Furthermore, there was no effect of the inactive analogue 1-(6-[17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl]aminohexyl)-2,5-pyrrolidinedione on recombinant PI-PLC activity or ABA-induced and external Ca2+-induced oscillations in [Ca2+]cyt and stomatal closure. This lack of effect suggests that the effects of U-73122 in guard cells are the result of inhibition of PI-PLC and not a consequence of nonspecific effects. Taken together, our data suggest a role for PI-PLC in the generation of ABA-induced oscillations in [Ca2+]cyt and point toward the involvement of oscillations in [Ca2+]cyt in the maintenance of stomatal aperture by ABA.     

Childhood predictors for high adult blood pressure. The Muscatine Study

In adult populations, elevated blood pressure is related to the development of stroke, renal disease, and occlusive atherosclerosis. The significance of blood pressure levels in childhood, unless extremely elevated, has not been related to disease outcomes. In a study carried out in Muscatine, Iowa, the risk of high blood pressure in young adult life was evaluated based on the observations of blood pressure and other factors made during the school-aged years. Subjects, 2445 in number, were first observed at ages 7 through 18 years and again between 20 and 30 years. During childhood, measurements of blood pressure, height, and weight were made on alternate years. At adult ages, the same measurements were again made and a health questionnaire was administered. Adult blood pressure was correlated with childhood blood pressure, body size, and change in ponderosity from childhood to adult life. Adult ponderosity was related to childhood ponderosity, and those who were most obese as adults showed the greatest increase in weight from their childhood years. These observations suggest that strategies to prevent the acquisition of excess ponderosity during childhood may be useful in preventing adult hypertension.