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Biomedical subjects

P M Keane

Publications and source records attributed to P M Keane.

At least 19 recordsLinked to original sources

Blood pressure and serum calcium responses to altered sodium intake in high renin hypertension.

Subjects with high renin hypertension tend to be sodium-resistant showing paradoxical blood pressure responses to alterations in sodium intake. Of twenty-five subjects with high renin essential hypertension (ten females, 15 males, mean age 30 years), 14 were noted to have a decrease in mean arterial blood pressure (MAP) when sodium intake was increased from 10 to 100 mmol/d. The percentage response of plasma renin activity was greater in these patients than in those with an increase in MAP (-55.4 +/- 5.4 v -33.6 +/- 6.9, P = .018). Overall, the response of MAP was directly correlated to the percentage response of plasma renin activity (r = .549, P = .005), and inversely related to the change in serum calcium concentration (corrected for changes in serum albumin) (r = -.547, P = .005). No intercorrelation between the changes in plasma renin activity and serum calcium concentration was detected. The blood pressure response to increased sodium intake in high renin hypertension would appear to be divergent and related not only to the suppression of plasma renin activity, but also to changes in circulating calcium.

Adult

Pericardial pressure attenuates release of atriopeptin in volume-expanded dogs.

The role of the pericardium in the release of atriopeptin (AP) was examined, utilizing two separate protocols, in alpha-chloralose-anesthetized dogs. Protocol I consisted of an experimental group (9 dogs), in which the pericardium was incised to allow instrumentation and reapproximated, and a control group (6 dogs), in which the pericardium was left undisturbed. In the experimental group, mean right atrial pressure (Pra) was elevated from a control value of 1.8 +/- 0.9 mmHg (mean +/- SD) to 8.3 +/- 0.8 mmHg for 40 min by volume expansion with isoncotic, lactated Ringer solution. After this period of volume expansion, the pericardium was removed while holding Pra at 8 mmHg. During volume expansion, arterial blood samples for AP analysis were taken at 5, 10, 15, 20, 30, and 40 min, pre- and postpericardiectomy. A similar protocol was followed in the control group. At a Pra of 8 mmHg prepericardiectomy, the plasma AP concentration was 76 +/- 17 pM/l and 74 +/- 38 pM/l in the experimental and control groups, respectively. However, after pericardiectomy, AP levels increased significantly in both the experimental group (136 +/- 41 pM/l; P less than 0.001) and the control group (107 +/- 53 pM/l; P less than 0.025). In protocol II (6 dogs), the pericardium was removed before volume expansion, and Pra was elevated by 2- to 3-mmHg increments and maintained for periods of 13 min at each pressure. AP concentration did not increase until Pra reached 3-4 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Flupenthixol and fluvoxamine in mild to moderate depression: a comparison in general practice.

Seventy-two depressed patients attending general practices were randomly allocated to treatment with either flupenthixol dihydrochloride (1 to 2 mg/day) or fluvoxamine maleate (100 to 200 mg/day) to assess efficacy and side-effects over a 4-week period. Clinical assessments were carried out before medication (Day 1) and on Days 8, 15 and 29 of treatment using the Hamilton Rating Scale for Depression, Clinical Global Impressions (CGI) and a patient self-assessment visual analogue scale for depression. Unwanted symptoms were also recorded. Reduction in mean total scores on the Hamilton scale at each assessment and therapeutic effect improvement on the CGI were greater for patients treated with flupenthixol (p less than 0.05). Reduction in unwanted symptoms was progressive in both groups, but more pronounced in patients receiving flupenthixol. Twice as many new symptoms arose in the fluvoxamine group compared to the flupenthixol group. Four patients were withdrawn in the fluvoxamine group due to untoward drug effects compared with none in the flupenthixol group.

Adolescent

Norepinephrine and calcium responses to altered sodium intake in modulating and non-modulating high-renin hypertension.

Sodium sensitivity in subjects with high-renin hypertension has been associated with non-modulation of cardiovascular and biochemical responses to alteration in sodium intake. Using the percentage suppression of plasma renin activity in response to an increase in dietary sodium intake, high-renin hypertensive subjects were categorized in two groups. In association with the increase in sodium intake, modulators showed greater than 58% suppression of plasma renin activity, and significant reductions in mean arterial pressure, plasma aldosterone, norepinephrine and serum calcium concentration. Non-modulators had no significant change in plasma renin activity, mean arterial blood pressure, plasma aldosterone, norepinephrine or serum calcium concentration. The blood pressure response to an increase in dietary sodium intake may be a composite of responses of the renin-angiotensin-aldosterone axis, the adrenergic nervous system and calcium regulatory system.

Aldosterone

Excessive growth of cultured beta cells from an adult patient with beta cell hyperplasia.

We have studied a 25-year-old female with frequent, severe hypoglycemic episodes. Concurrent with low serum glucose levels, the concentrations of C-peptide and insulin were markedly elevated. Tests for sulfonylurea hypoglycemic agents were negative. Special tests did not disclose any neoplasm. Biopsy of the pancreatic tail revealed islet cell hyperplasia and adenomatosis. About two-thirds of the pancreas was resected, resulting in correction of all metabolic abnormalities. Specific fluorescein-labeled anti-insulin antibodies revealed staining in 60-80% of the cultured cells isolated from the patient's pancreas, while electron microscopy disclosed insulin storage granules in about 80%. By comparison, for each of these findings, the range for cells from normal pancreases was 30-50%. In contrast to these control cells, cells from the patient grew about 2 and 2.6 times more rapidly during the first two cell cycles, and the growth persisted through four cycles. The greater and more enduring growth of the patient's cells in culture must have been at least partly independent of circulating factors. Paracrine/autocrine principles from the beta cells or other islet cells may have been responsible.

Adult

Studies of thyroxine binding to plasma proteins in health and disease.

Thyroxine binding protein characteristics were defined in 6 normal subjects, 4 with thyroxine binding globulin (TBG) deficiency, 3 with TBG increase, one with hyperthyroxinemic dysalbuminemia, 7 with severe non-thyroidal illness, and 3 with chronic renal failure. Free thyroxine was measured by Sephadex partition in plasma to which increasing thyroxine concentrations were added. Deconvolution of the resultant titration data was performed by computer modelling. Abnormalities of thyroxine binding capacities or of binding affinities occur in non-thyroidal illness, chronic renal failure, and sporadically. The patient with hyperthyroxinemic dysalbuminemia had increased thyroxine binding affinity to thyroxine binding prealbumin as well as to albumin. "Free-T4 assays" or estimates of Free-T4 by calculation from total thyroxine and measures of protein binding such as T3-uptake must be expected to be perturbed by these binding protein abnormalities unless such interferences are explicitly demonstrated to be absent.

Adult

Lung angiotensin converting enzyme activity in chronically hypoxic rats.

A study was carried out to test the hypothesis that the reduced lung angiotensin converting enzyme (ACE) activity which occurs in chronic hypoxia is related to the development of pulmonary hypertension rather than to hypoxia per se. Right ventricular mean systolic pressure (Prvs, mm Hg) and ACE activity (nmol/mg protein/min) in lung tissue homogenates were measured in seven groups of four rats placed in a hypobaric chamber (380 mm Hg; 51 kPa) for two to 24 days. Identical measurements were made on 11 groups of four rats, which were placed in the chamber for 24 days and then allowed to recover in room air for one to 153 days. After two days of hypoxia the mean Prvs (25.5 (SD 3.7] and the mean lung ACE activity (56 (4.6] did not differ significantly from control values. Exposure to hypoxia for four to 24 days caused a progressive increase in mean Prvs to 44.4 (5.9) and a progressive reduction in mean lung ACE activity to 34 (4.0). During recovery lung ACE activity increased and Prvs decreased, so that normal values were achieved by 15 and 56 days respectively. Decreased lung ACE activity may be related to haemodynamic factors associated with pulmonary hypertension rather than to hypoxia.

Animals

Pulmonary hypertension induced in rats by monocrotaline and chronic hypoxia is reduced by p-chlorophenylalanine.

We have studied the role of 5-hydroxytryptamine (5-HT) in monocrotaline pulmonary hypertension and chronic hypoxic pulmonary hypertension in rats using p-chlorophenylalanine (PCPA) which inhibits 5-HT synthesis. We measured right ventricular mean systolic pressure (Prvs), right ventricular hypertrophy, medial thickness of muscular pulmonary arteries, and muscularization of pulmonary arterioles 17 days after a single dose of monocrotaline (60 mg/kg) and after 26 days of chronic hypobaric hypoxia (380 mm Hg). In monocrotaline pulmonary hypertension, pretreatment with PCPA (500 mg/kg) was associated with significant reductions (p less than 0.05) in Prvs (29%), right ventricular hypertrophy (33%), and medial thickness of muscular pulmonary arteries (14%). In chronic hypoxic pulmonary hypertension, pretreatment with PCPA was associated with significant reductions in Prvs (20%), right ventricular hypertrophy (28%), medial thickness of muscular pulmonary arteries (14%), and muscularization of pulmonary arterioles (47%). 5-HT may play a role in the development of monocrotaline pulmonary hypertension and chronic hypoxic pulmonary hypertension in rats.

Animals

Hypertension and unilateral vascular occlusion. Diagnosis and surgical intervention.

Four hypertensive patients with unilateral atheromatous renal arterial occlusion have been studied. Each showed elevation of renal venous activity on the side of the vascular occlusion relative to the opposite side. Three of the patients underwent nephrectomy with amelioration of their hypertension. It is concluded that surgical treatment is valid therapy in patients with atheromatous unilateral renal vascular occlusion and ipsilateral elevation of renal venous renin activity.

Aged

Renin, aldosterone, electrolyte, and cortisol responses to hypoxic decompression.

Responses of plasma renin activity, plasma aldosterone, plasma cortisol, and plasma electrolyte concentration and urinary electrolyte and aldosterone excretion were studied in four men during hypoxic decompression to a stimulated altitude of 4,760 m in a pressure chamber. Three of the four subjects developed significant acute mountain sickness. Plasma sodium and potassium concentrations were unchanged. No significant change in plasma renin activity was observed, but values tended to fall. Plasma aldosterone concentration was depressed while plasma cortisol was elevated and diurnal variation lost. Urinary sodium excretion was unchanged, but urinary potassium and aldosterone excretion were decreased. The decrease in plasma and urinary aldosterone and urinary potassium in the absence of change in plasma renin activity or plasma potassium is of uncertain origin. It is unlikely to be due to a decrease in adrenocorticotropin secretion since plasma cortisol rose during the same time. None of the changes could be causally implicated in the development of acute mountain sickness although the increase in plasma cortisol was greatest in the most ill.

Adult

Thermodynamic aspects of some radioassays.

In a number of radioimmunoassays and radiotransin assays, effective equilibrium constants have been measured at different temperatures in order to define the relative contribution of changes of entropy and enthalpy to the change in free binding energy. In systems with a large enthalpy component, the lowest possible incubation temperature maximizes sensitivity, and control of temperature throughout the assay is important. Conversely, when enthalpy change is small, a high temperature allows rapid attainment of equilibrium without loss of sensitivity. At a theoretical level, the thermodynamic characteristics of binding may allow some insight into the nature of the binding process.

Angiotensin II

Rapid, specific assay for plasma cortisol by competitive protein binding.

We describe a modified competitive protein-binding method for assay of plasma cortisol. Plasma samples are deproteinized by dilution with an ethanol/phosphate buffer, followed by heating at 100 degrees C for 2 min. Horse serum is used as the source of transcortin. Free radioactivity is separated from the protein-bound component by partition into liquid scintillation counting within 60 min. The assay has better specificity and precision than a competitive protein-binding assay in which ethanol extraction and Florisil adsorbent are used, and results correlate well with those of a specific radioimmunoassay method.

Binding, Competitive