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Biomedical subjects

J A Oates

Publications and source records attributed to J A Oates.

At least 91 records · Page 5Linked to original sources
PubMed1985

Urinary kallikrein and systemic prostacyclin synthesis during sodium chloride infusion in normal man.

An intravenous infusion of 3 litres of sodium chloride solution (saline: 150 mmol/l) was given over 1 h to normal subjects. During and immediately after the infusion, renal plasma flow increased in the majority of subjects, but the rise was not statistically significant. Significant increases in urine flow, sodium excretion, urinary kallikrein excretion and urinary excretion of dinor-6-keto prostaglandin (PG) F1 alpha, a measure of systemic PGI2 synthesis, were noted. Plasma renin activity and plasma protein concentration were significantly lowered by the infusion. At 2 h after the end of the infusion, although urine flow fell significantly, sodium excretion had not decreased. The reduction in plasma renin activity and plasma proteins persisted, and excretion of kallikrein and the PGI2 metabolite returned to control values. Overall, urinary kallikrein excretion correlated significantly with urine flow and with sodium excretion. Peak kallikrein excretion occurred in the second 30 min of the infusion, and preceded maximal urine flow and sodium excretion. The results suggest that increased systemic synthesis of PGI2 occurs in response to an acute infusion of sodium chloride, and may be an adaptive response of the vasculature to volume expansion. They support a role for the renal kallikrein-kinin system in the early diuretic and natriuretic response to saline infusion; the reduction in plasma renin activity and plasma protein concentration may be involved in both the early response and the persistent natriuresis 2 h after the infusion.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Two-dimensional echocardiography in the diagnosis of carcinoid heart disease.

Tricuspid valve disease accounts for significant morbidity and mortality in the carcinoid syndrome, but M-mode echocardiography is often insensitive in completely defining the tricuspid valve. We performed two-dimensional echocardiography (2DE) in seven patients with proven carcinoid syndrome. There were five males and two females whose ages ranged from 53 to 79 years. The carcinoid syndrome had been present by symptoms for 12 to 84 months and by 5-HIAA levels for 6 to 84 months prior to 2DE. Short, thickened, immobile tricuspid valve leaflets, fixed in a partially open position, were visualized in two patients and confirmed in one patient at surgery. Tricuspid regurgitation was demonstrated angiographically in one and by contrast 2DE in the other. A third patient had clinical evidence of tricuspid stenosis with a doming tricuspid valve on 2DE. The motion of the tricuspid value viewed in real time was clearly distinct in these two situations. Four patients had both normal M-mode and 2DE studies despite the fact that clinical and biochemical evidence of carcinoid disease had been present for equally long periods of time. The tricuspid valve was best visualized in the parasternal right ventricular long-axis and short-axis views. The apical four-chamber view was less helpful. Thus, 2DE demonstrated specific tricuspid valve abnormalities in the carcinoid syndrome with thickening, shortening, and immobility of the leaflets when valvular regurgitation was present and thickening and doming when the valve was stenotic. 2DE should be a useful method in the diagnosis and sequential evaluation of patients with carcinoid heart disease.

Aged↗
PubMed1984

Accurate and efficient method for quantification of urinary histamine by gas chromatography negative ion chemical ionization mass spectrometry.

Because of the recognized inaccuracy and unreliability of currently available methods for the quantification of histamine in biological fluids, a method for quantification of urinary histamine by stable isotope dilution assay with negative ion chemical ionization mass spectrometry has been developed. Following the addition of [2H4]histamine to 1 ml of urine, histamine is extracted into butanol, back-extracted into HCl, derivatized to the pentafluorobenzyl derivative (CH2C6F5)3-histamine, extracted into methylene chloride, and then quantified with negative ion chemical ionization mass spectrometry by selected ion monitoring of the ratio of ions m/z430/434. Twenty samples can be assayed in 2 days. Precision of the assay is +/- 2.7% and the accuracy is 97.6%. Lower limits of sensitivity are approximately 100-500 fg injected on-column. This assay provides a very sensitive, accurate, and efficient method for the quantification of histamine in human urine.

Fluorescent Dyes↗
PubMed1984

Metabolism of leukotriene B4 in the monkey. Identification of the principal nonvolatile metabolite in the urine.

Five milligrams of [5,6,8,9,11,12,14,15-3H8]-leukotriene B4 (LTB4) (1.68 Ci/mmol) were infused into a monkey over a three hour period. Twenty-five per cent of the infused 3H-activity was recovered in the urine during the twenty hours of collection. Plasma and urinary metabolite volatility studies revealed that in contrast to previously studied eicosanoids, more than 70% per cent of the infused LTB4 3H-label was converted to tritiated water. The major nonvolatile urinary metabolite of LTB4 representing 0.8% of the infused material was identified as 20-OH-LTB4. LTB4 was not excreted in the urine. Other nonvolatile metabolites of LTB4 representing less than 0.4% each of the infused material were isolated from the urine. While there was an adequate quantity of some of these metabolites for partial characterization, there was insufficient material for structural elucidation. Further studies were performed in rabbits in which either LTB4 or the structurally related compound 8,15-dihydroxyeicosatetraenoic acid (8,15-diHETE) were infused intravenously. In these rabbits the metabolism of LTB4 and 8,15-diHETE was similar to that in the monkey with greater than 80% of the infused 3H-activity converted to tritiated water. These studies suggest that leukotriene B4 and structurally related compounds undergo extensive degradation in vivo via the beta-oxidation system.

Animals↗
PubMed1984

Selective and nonselective inhibition of thromboxane formation.

Thromboxane A2, the predominant cyclooxygenase product of arachidonic acid in the platelet, is a potent vasoconstrictor and stimulus of platelet aggregation. Prostacyclin, the principal cyclooxygenase metabolite formed in the vascular endothelium, inhibits platelet aggregation and dilates blood vessels. A therapeutic objective in the treatment of human vascular occlusive disease has been the inhibition of thromboxane formation without coincident reduction in prostacyclin biosynthesis. We compared the biochemical selectivity and platelet inhibitory actions of single doses of aspirin, a cyclooxygenase inhibitor, with imidazo(1,5-2)pyridine-5-hexanoic acid (CGS 13080), an inhibitor of thromboxane synthase. Aspirin, 325 mg, prolonged the bleeding time markedly, inhibited aggregation and nucleotide release in whole blood and platelet-rich plasma, and maximally inhibited thromboxane generation in serum. The effects of aspirin, 20 mg, were considerably less marked but, as with the higher dose, persisted throughout the study period (24 hr after dosing). CGS 13080 also prolonged bleeding time and inhibited thromboxane formation. In contrast to aspirin, these effects were reversible and inhibition of aggregation was less marked. Endogenous prostacyclin biosynthesis was measured by excretion of the major urinary metabolite 2,3-dinor-6-keto-PGF1 alpha (PGI-M). Whereas aspirin, 325 mg, reduced PGI-M excretion a mean 29%, excretion increased 48% and 100% after CGS 13080, 100 mg and 200 mg. Aspirin, 20 mg, did not alter prostacyclin biosynthesis. Inhibition of thromboxane synthase permits selective inhibition of thromboxane formation in man. Although drugs of greater potency and longer duration of action are desirable, enhanced prostacyclin synthesis may be an important component of the platelet inhibitory actions of thromboxane synthase inhibitors in man.

Aspirin↗
PubMed1984

Operative management of renovascular hypertension. Results after a follow-up of fifteen to twenty-three years.

From March 1960 through January 1968, 71 patients underwent operations for renovascular hypertension at our center. There were three operative deaths in 94 procedures. Primary nephrectomy was performed in 26 patients. Attempted revascularization of 62 kidneys was successful in 46 (74%). In 13 (87%) of the 15 cases considered operative failures, the patients underwent either secondary nephrectomy (11) or repeat revascularization (two). Based on the results of the final operation, initial blood pressure response (1 to 6 months postoperatively) in the surviving patients indicated 44% cured (30 patients), 40% improved (27), and 16% unchanged (11). The sequential clinical, functional, and anatomic follow-up evaluations to time of death or to date are available in 66 of the 68 patients (97%) who survived operation and form the basis of this report. Fifteen- to 20-year arteriographic follow-up in 16 patients revealed one late neointimal anastomotic stenosis and an additional three aortic suture line false aneurysms in Dacron aortorenal grafts. During this 15- to 23-year follow-up, 71% of atherosclerotic (AS) patients and 23% of fibromuscular dysplasia (FMD) patients died. Cardiovascular (CV) morbid events occurred in 77% of AS patients and in 19% of FMD patients. The cumulative incidence of death and CV morbid events during follow-up is examined by Kaplan-Meier life tables and Cox's proportional hazards regression analysis in these respective groups to identify preoperative markers predictive of longer event-free survival in relation to blood pressure benefit by operation (for example, focal vs. diffuse AS, presence of cerebrovascular disease, ischemic heart disease, left ventricular hypertrophy seen by electrocardiography, azotemia, smoking, diabetes, and hyperlipidemia).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Encainide and its metabolites. Comparative effects in man on ventricular arrhythmia and electrocardiographic intervals.

To assess the relative contributions of encainide and its putatively active metabolites, O-demethyl encainide (ODE) and 3 methoxy-O-demethyl encainide (3MODE), to the drug's pharmacologic effects, we compared intravenous infusions and sustained oral therapy in two phenotypically distinct groups of patients, extensive and poor metabolizers of encainide. Unlike poor metabolizers, extensive metabolizers had appreciable quantities of both metabolites detectable in plasma and had fourfold shorter elimination half-lives for encainide. By quantitating electrocardiogram intervals, arrhythmia frequency, and plasma concentrations, we found that, in poor metabolizers, arrhythmia suppression and ventricular complex (QRS) prolongation were correlated positively with encainide concentrations (r greater than or equal to 0.570, P less than 0.014). In these two subjects, antiarrhythmic concentrations of encainide (greater than 265 ng/ml) were at least fivefold higher than those sustained in the six extensive metabolizers during steady state oral therapy. In extensive metabolizers, encainide concentrations were uncorrelated with effects. Arrhythmia suppression and QRS prolongation in extensive metabolizers correlated best with ODE (r greater than or equal to 0.816, P less than 0.001); QTc change correlated positively with both 3MODE and ODE. Arrhythmia suppression paralleled QRS prolongation; the relationship between them appeared similar in both phenotypic groups. In most patients, extensive metabolizers, encainide effects during oral therapy are mediated by metabolites, probably ODE.

Aged↗
PubMed1984

Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4.

Leukotriene B4 (LTB4) is a potent primary stimulator of neutrophil chemotaxis, aggregation, and degranulation and induces superoxide production at higher concentrations. In order to determine whether LTB4 modulates neutrophil responses to oxidative stimuli, human neutrophils (PMNs) were incubated with LTB4 prior to stimulation with f-Met-Leu-Phe (fMLP, 10(-7) mol/L), opsonized zymosan (OZ, 250 micrograms/mL), or phorbol myristate acetate (PMA, 32 nmol/L). Superoxide (O2-) production by stimulated PMNs was assessed by the superoxide dismutase-inhibitable reduction of cytochrome c. LTB4 alone did not stimulate O2- production in concentrations below 10(-7) mol/L and had no effect on the O2- assay. In the concentration range of 10(-12) to 10(-8) mol/L, LTB4 did not alter O2- release induced by OZ or PMA. In contrast, LTB4-treated cells demonstrated enhanced O2- production following exposure to fMLP, and in the presence of 10 nmol/LLTB4, generated 180% +/- 41% of O-2 quantities produced by control cells (n = 23). Enhancement was LTB4 dose-dependent, was maximal in the range of 1 to 10 nmol/L LTB4, was not reversed by removal of the lipid from the medium prior to fMLP stimulation, and was not dependent on the presence of Ca++ or Mg++ in the suspending medium. Chemiluminescence of fMLP-stimulated neutrophils was increased to 323% of controls in neutrophils preincubated with 10 nmol/L LTB4. Unlike augmentation of oxidative responses to fMLP seen with other degranulating stimuli, enhancement by LTB4 was not correlated with an increase in 3H-fMLP receptor binding. These results indicate that, in addition to its primary effects on neutrophil function, LTB4 modulates PMN oxidative responses to the chemotactic peptide and, thus, may amplify the release of oxygen metabolites at inflammatory foci.

Chemotactic Factors↗
PubMed1983

Systemic prostaglandin I2 synthesis is normal in patients with Bartter's syndrome.

Urinary excretion of 2, 3 dinor-6-keto-PGF1 alpha, a metabolite of prostacyclin (PGI2), was measured in 9 patients with Bartter's syndrome. The rate of excretion of this metabolite was normal in these patients during ingestion of both a normal and high dietary intake of potassium. This suggests that in Bartter's syndrome the rate of entry of PGI2 into the circulation is normal. Excessive systemic synthesis of PGI2 is therefore unlikely to be an explanation for either the vascular insensitivity to angiotensin II or the defect in platelet aggregation characteristic of the syndrome.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Identification of lipoxygenase products from arachidonic acid metabolism in stimulated murine eosinophils.

The presence of arachidonic acid lipoxygenase pathways in murine eosinophils was demonstrated by the isolation and identification of several lipoxygenase products from incubations of these cells. The most abundant arachidonate metabolite from murine eosinophils stimulated with ionophore A23187 and exogenous arachidonic acid was 12-S-hydroxyeicosatetraenoic acid (12-S-HETE), and the next most abundant was 15-HETE. Two families of leukotrienes were also recovered from these incubations. One family comprised the hydrolysis products of leukotriene A4, and the other included products derived from the 14,15-oxido analog of leukotriene A4 (14,15-leukotriene A4). Two double oxygenation products of arachidonate were also identified. These compounds were a 5,15-dihydroxyeicosatetraenoic acid (5,15-diHETE) and a 5,12-dihydroxyeicosatetraenoic acid (5,12-diHETE). Eosinophil stimulation promoter is a murine lymphokine which enhances the migration of eosinophils. When murine eosinophils were incubated with eosinophil stimulation promoter in concentrations sufficient to produce a migration response, a 2-3-fold increase in the production of 12-HETE was observed compared to unstimulated cells. Coupled with the recent demonstration that arachidonic acid lipoxygenase inhibitors suppress the migration response to eosinophil stimulation promoter and that 12-HETE induces a migration response, this observation provides further evidence in support of the hypothesis that eosinophil stimulation promoter stimulation of eosinophils results in the generation of lipoxygenase products which modulate the migratory activity of the cells.

Animals↗
PubMed1983

Intervention with epinephrine in hypotension associated with mastocytosis.

The occurrence of the episodes of vasodilatory hypotension can be a life-threatening manifestation of systemic mastocytosis. This article describes the reversal by epinephrine of episodes of severe hypotension in two hospitalized patients with mastocytosis. Recognition of the efficacy of epinephrine in hypotension associated with mastocytosis can be important when other methods fail to restore hemodynamic stability.

Aged↗