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Biomedical subjects

K Berman

Publications and source records attributed to K Berman.

At least 19 recordsLinked to original sources

Double-blind crossover study of the interaction between perindopril and amlodipine on blood pressure and hormones related to fluid and electrolyte balance in patients with essential hypertension.

This study was to investigate the interaction between low doses of perindopril (2 mg daily) and amlodipine (2.5 mg daily) on ambulatory blood pressure (BP), clinic BP, serum angiotensin-converting enzyme (ACE), plasma levels of renin (PRA), angiotensin II (Ang II), aldosterone, and atrial natriuretic peptide (alpha-h ANP) in subjects with essential hypertension. The study design was a parallel, two-period, placebo-controlled, double-blind crossover design, with 11 subjects receiving perindopril and 10 receiving amlodipine during the run-in phase. The addition of amlodipine to perindopril had no effect on ambulatory BP, whereas the addition of perindopril to amlodipine reduced both systolic (P = 0.027) and diastolic (P = 0.049) ambulatory BP. By contrast, the opposite result was obtained for clinic BP at trough, whereby the addition of amlodipine to perindopril reduced erect systolic BP (P = 0.036) and both supine and erect diastolic BP (P = 0.038) whereas the addition of perindopril to amlodipine was without effect. The addition of perindopril to amlodipine decreased serum ACE by 72% and increased PRA two-fold, without change in plasma levels of Ang II, aldosterone or alpha-h ANP. The addition of amlodipine to perindopril increased plasma aldosterone 1.7-fold but did not affect serum ACE, PRA, Ang II, or alpha-h ANP. These interactions between perindopril and amlodipine may have been conditioned by the specific effects of the therapy first given, as well as by the different circumstances of BP measurement (ambulatory vs clinic).

Adult

Expression of voltage-gated potassium channels decreases cellular protein tyrosine phosphorylation.

Protein tyrosine phosphorylation by endogenous and expressed tyrosine kinases is reduced markedly by the expression of functional voltage-gated potassium (Kv) channels. The levels of tyrosine kinase protein and cellular protein substrates are unaffected, consistent with a reduction in tyrosine phosphorylation that results from inhibition of protein tyrosine kinase activity. The attenuation of protein tyrosine phosphorylation is correlated with the gating properties of expressed wild-type and mutant Kv channels. Furthermore, cellular protein tyrosine phosphorylation is reduced within minutes by acute treatment with the electrogenic potassium ionophore valinomycin. Because tyrosine phosphorylation in turn influences Kv channel activity, these results suggest that reciprocal modulatory interactions occur between Kv channel and protein tyrosine phosphorylation signaling pathways.

Cells, Cultured

Tyrosine phosphorylation modulates current amplitude and kinetics of a neuronal voltage-gated potassium channel.

The modulation of the Kv1.3 potassium channel by tyrosine phosphorylation was studied. Kv1.3 was expressed in human embryonic kidney (HEK 293) cells, and its activity was measured by cell-attached patch recording. The amplitude of the characteristic C-type inactivating Kv1.3 current is reduced by >95%, in all cells tested, when the channel is co-expressed with the constitutively active nonreceptor tyrosine kinase, v-Src. This v-Src-induced suppression of current is accompanied by a robust tyrosine phosphorylation of the channel protein. No suppression of current or tyrosine phosphorylation of Kv1.3 protein is observed when the channel is co-expressed with R385A v-Src, a mutant with severely impaired tyrosine kinase activity. v-Src-induced suppression of Kv1.3 current is relieved by pretreatment of the HEK 293 cells with two structurally different tyrosine kinase inhibitors, herbimycin A and genistein. Furthermore, Kv1.3 channel protein is processed properly and targeted to the plasma membrane in v-Src cotransfected cells, as demonstrated by confocal microscopy using an antibody directed against an extracellular epitope on the channel. Thus v-Src-induced suppression of Kv1.3 current is not mediated through decreased channel protein expression or interference with its targeting to the plasma membrane. v-Src co-expression also slows the C-type inactivation and speeds the deactivation of the residual Kv1.3 current. Mutational analysis demonstrates that each of these modulatory changes, in current amplitude and kinetics, requires the phosphorylation of Kv1.3 at multiple tyrosine residues. Furthermore, a different combination of tyrosine residues is involved in each of the modulatory changes. These results emphasize the complexity of signal integration at the level of a single ion channel.

DNA, Complementary

Some factors associated with mortality in perforated peptic ulcer: a case-control study.

This study examined the associations of individual coexisting illnesses, septicaemia, intra-abdominal abscess, marital status, smoking and alcohol use, with mortality following perforation of peptic ulcer without pre-operative evidence of haemorrhage. Patients who died in hospital following ulcer perforation (cases; n = 300) were compared with patients who survived following ulcer perforation (controls; n = 276). The controls were frequency-matched to the cases on age, sex and perforation site. Data were analysed by logistic regression. Cardiac, respiratory, cerebrovascular, renal, liver and malignant diseases, and septicaemia and intra-abdominal abscess were associated with mortality and the coexisting illnesses were significantly increased in cases compared to controls both on admission and at the end of hospital stay. During hospitalization, the odds of pneumonia decreased in cases, otherwise there was little change in strengths of associations over this period. Being widowed or never married was positively associated with mortality, and moderate alcohol use was negatively associated. In conclusion, this study identifies several coexisting illnesses, septicaemia and intra-abdominal abscess as risk factors for mortality following ulcer perforation. The results suggest that, with little exception, the same level of mortality risk is associated with coexisting illnesses whether the beginning or end of hospital stay is used as the index time point.

Abdominal Abscess

Triiodothyronine improves left ventricular function without oxygen wasting effects after global hypothermic ischemia.

Cardiopulmonary bypass results in a "euthyroid sick" state. Recently, interest has focused on the relationship between low serum triiodothyronine levels and postoperative cardiovascular hemodynamics. The present study was undertaken to more clearly define the acute effects of triiodothyronine on myocardial mechanics and energetics after hypothermic global ischemia using an ex-vivo canine heart preparation to model the clinical condition. Experiments were performed on isolated hearts subjected to hyperkalemic arrest with 90 minutes of hypothermic (10 degrees C) ischemia. Isolated hearts were cross-perfused by euthyroid support dogs in which triiodothyronine levels spontaneously decreased by 65% to 75% (p < 0.01) after the initiation of cross-perfusion. In nine heart preparations, triiodothyronine (Triostat) was given as a bolus dose (0.2 micrograms/kg) after 1 hour of baseline data collection with a subsequent measurable rise in serum triiodothyronine levels (p < 0.01). In six postischemic hearts, reverse triiodothyronine was given as a 0.2 micrograms/kg bolus. Triiodothyronine was also administered to a group of eight nonischemic, continuously perfused isolated hearts. Intrinsic myocardial contractility was assessed by analysis of the preload recruitable stroke work area, energetic efficiency from the myocardial oxygen consumption-pressure-volume area relationship, and coronary vascular resistance from analysis of coronary flow and perfusion pressure. Acute administration of triiodothyronine to postischemic hearts improved the preload recruitable stroke work area from 9.5 +/- 1.42 to 14.9 +/- 2.03 x 10(7) erg/ml, a 56% increase from baseline (p < 0.001), but had no effect on the preload recruitable stroke work area of the nonischemic hearts. The inotropic response resulting from triiodothyronine treatment did not alter the myocardial oxygen consumption-pressure-volume area relationship. Triiodothyronine treatment was associated with significantly decreased coronary resistance and increased coronary flow through a range of diastolic loading conditions in the postischemic hearts. The biologically inactive thyroid hormone metabolite reverse triiodothyronine was without effect on any of the measured parameters. On the basis of these results, we conclude that the low triiodothyronine state of cardiopulmonary bypass can be reproduced in this isolated heart model and that acute triiodothyronine treatment results in a unique inotropic action manifest only in the postischemic reperfused myocardium and is accomplished without oxygen wasting effects.

Animals

Constant observation: implications for nursing practice.

1. Constant observation is an increased level of observation and supervision in which continuous one-to-one monitoring techniques are utilized to assure the safety and well-being of an individual patient or others in the patient care environment. 2. Individuals who provide constant observation vary widely among health care facilities; but ultimately are the responsibility of the registered nurse. There are many areas that must be addressed by institutions when considering the use or implementation of constant observation. These include: measuring the associated costs, risk management, role development, orientation of employees, and performance evaluation. 3. The changing health care environment and public concern over the quality of health care and risk management require nursing administrators to consider risk-benefit and cost-benefit analyses related to constant observation. There is continued need for protocol and policy development, as well as for guidelines and orientation of staff regarding constant observation.

Cost-Benefit Analysis

Eating attitudes in seasonal affective disorder and bulimia nervosa.

Markedly increased appetite and eating are commonly found in seasonal affective disorder (SAD) and bulimia nervosa (BN). To investigate dysfunctional eating attitudes, we administered the Eating Disorders Inventory (EDI), a self-rating questionnaire that assesses abnormal eating attitudes and behaviours, to 30 female SAD patients, 30 matched BN patients, and 30 non-clinical subjects. The SAD patients had higher scores on most EDI subscales compared to the non-clinical subjects; the BN patients had higher scores than the SAD patients on only two of three EDI subscales that are specific to eating disorders. These data add to the evidence supporting a clinical overlap between SAD and BN.

Adult

Ischemic tolerance of the arrested heart during warm cardioplegia.

Normothermic blood cardioplegia has recently generated interest as an alternative method of myocardial protection during cardiopulmonary bypass (CPB) surgery. One disadvantage is the obligatory interruption of coronary flow during the distal coronary anastomosis. This study was designed to determine the safe normothermic ischemic time of the arrested and decompressed heart. Under normothermic CPB (37 degrees C), initial cardioplegic arrest was induced with 750 cc of warm (37 degrees C) hyperkalemic blood cardioplegia in 21 adult dogs. The heart then received warm blood cardioplegia either continuously (50 cc/min), every 5 min (250 cc each) or every 10 min (350 cc each) for a total equivalent ischemic time of 30 min (n = 7 in each group). Left ventricular pressure-volume (PV) loops were measured by micromanometer and conductance (volume) catheters before, at 60 and 90 min after aortic cross-clamping. Systolic function was measured as the preload recruitable stroke work area derived from the stroke work-end diastolic volume relationship, and the diastolic stiffness constant (k) was derived from the exponential diastolic PV relationship. The q5 min group sustained minor deterioration in diastolic function while its systolic function was well maintained during recovery. There were significant reductions in both the diastolic and systolic functions in the q10 min group. The maximum drops in the septal wall pH during aortic cross-clamping were 0.05 +/- 0.02 (not significant), 0.19 +/- 0.06 (P < 0.05), and 0.40 +/- 0.09 (P < 0.01) for the continuous, q5 min and q10 min groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium

Trends in peptic ulcer mortality in Sydney from 1971 to 1987.

Gastric and duodenal ulcer (GU,DU) mortality in Western countries has varied over time by age and sex. Temporal variation raises the question of whether these ulcers have an environmental etiology. Using death certificate data, we investigated peptic ulcer mortality time trends from 1971 to 1987 in Sydney, Australia, and whether ulcer mortality and overall mortality in Sydney were similar with regard to time trends and associations with demographic and environmental factors. In men in all age groups and in women age < 65, GU and DU mortality decreased. In women age > or = 70, GU mortality remained constant and DU mortality increased. Average age at ulcer death increased: from 1971 to 1987, ulcer deaths at age > or = 70 rose from 52 to 80% of all ulcer deaths. In men who died at age 30-54, GU and DU mortality decreased relative to overall mortality. In women who died at age > or = 55, DU mortality increased relative to overall mortality. Compared with overall mortality, the ulcer mortality rate was affected more adversely by lower social class and lack of the marriage tie, and smoking rates tended to correlate more strongly with GU mortality. The greater-than-expected decrease in GU and DU mortality in younger men and the increase in DU mortality in elderly women suggest important changes in as yet unidentified environmental risk factors for ulcer mortality within the young adult male and elderly female general populations.

Adult

The effects of amrinone versus dobutamine on myocardial mechanics and energetics after hypothermic global ischemia.

The effects on the postischemic myocardium of amrinone and dobutamine were studied in canine hearts that underwent 90 minutes of hypothermic (10 degrees C) arrested ischemia. In an isolated heart preparation cross-circulated by a support dog, left ventricular pressure-volume loops were collected under a constant afterload based on a mock circulatory system and a range of preload conditions controlled by a computerized servo volume pump. Dobutamine (0, 5, 10, 15 micrograms/kg per minute) and amrinone (0, 0.75, 1.5, 3.0 mg/kg) were tested in this order based on the weights of the support dogs in eight experiments. Changes in intrinsic myocardial contractility were analyzed as percent increases in the preload recruitable stroke work area from baselines. Dobutamine exhibited significant dose-related increases in the preload recruitable stroke work area. Amrinone did not produce significant increases in preload recruitable stroke work area at 0.75 mg/kg; amrinone's inotropic effect was equivalent to dobutamine, 5 micrograms/kg per minute at 1.5 mg/kg, and at the maximum dose (3.0 mg/kg) it was equivalent to dobutamine, 10 micrograms/kg per minute. The myocardial energetic efficiency was determined from the analysis of the myocardial oxygen consumption-pressure volume area relationship. The y intercept represents the basal metabolic oxygen requirement of the unloaded beating heart, and the slope is inversely proportional to the rate of energy conversion for increasing loading conditions. Dobutamine significantly increased the y intercepts, but it had no effects on the slopes. These changes demonstrate reduced myocardial efficiencies that are consistent with previous reports. Amrinone (0.75 and 1.50 mg/kg) did not result in change of the y intercepts and the slopes of myocardial oxygen consumption-pressure-volume area relationship from baseline conditions. The y intercept was increased with amrinone (3.0 mg/kg), although still not significantly higher than baseline and not to the extents of the dobutamine group. Dobutamine did not have any primary effect on coronary resistance, while amrinone significantly reduced coronary resistance in all loading conditions at 1.5 and 3.0 mg/kg. This study demonstrates that the inotropic effects of amrinone tested under this constant afterload preparation were lower than those of dobutamine. Amrinone has a superior profile of myocardial efficiency on the postischemic myocardium since it does not produce the oxygen-wasting effects of the traditional inotropic agents such as the beta agonists. This benefit, together with amrinone's coronary dilating effects, critically improves the supply/demand ratio that may be of importance in certain clinical situations.

Amrinone

Middle cerebral artery reconstruction.

The authors have conducted an experimental study of the microanatomic features of the middle cerebral artery in unfixed human brains to assess the feasibility of reconstructive procedures within the Sylvian fissure. It was found that reconstructive procedures within the Sylvian fissure such as end-to-end, end-to-side, side-to-side, and grafting procedures were possible according to the anatomic data provided by our study. Possible surgical solutions to theoretical pathologic situations involving the middle cerebral artery vascular tree are highlighted and their feasibility is discussed.

Cerebral Arteries