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Biomedical subjects

J M Clarke

Publications and source records attributed to J M Clarke.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effect of simple short term dietary control on urine electrolyte excretion in normal men.

Normal diet and a simple short term prescribed diet were compared with respect to mean excretion of urine electrolytes and the variability in these responses in 12 healthy male subjects. Urine was collected from 7 to 15 h (overnight) and 15 to 25 h (daytime) after the start of dietary control. Differences in mean responses were slight. For sodium and potassium excretion, however, there were tendencies for responses in subjects with high excretion on normal diet to decrease and for responses in those with low excretion on normal diet to increase towards the overall mean during the prescribed diet. The prescribed diet reduced markedly the variability in electrolyte responses and for log transformed data reductions in variability were statistically significant in the daytime urine collections. The results of this study have confirmed quantitatively the benefit of a short period of simple dietary control. The marked reduction in the variability of sodium and potassium excretion improves considerably the precision and sensitivity of studies of urine electrolyte composition.

Adult↗
PubMed1985

Assessment of myocardial function before aortic surgery by radionuclide angiocardiography.

A consecutive series of 41 patients undergoing elective aortic surgery had pre-operative assessment of cardiac function by radionuclide angiocardiography. Their subsequent progress was monitored. There were 4 patients whose pre-operative left ventricular ejection fraction was less than 30 per cent and 3 of these patients died of cardiac failure postoperatively. There was only 1 death from cardiac failure amongst the 37 patients whose pre-operative left ventricular ejection fraction was less than 30 per cent. Radionuclide angiocardiography is an accurate indicator of myocardial function of patients before major aortic surgery.

Aged↗
PubMed1985

Intestinal function and intestinal blood supply: a 20 year surgical study.

The experience of The Middlesex Hospital in the investigation and management of chronic intestinal arterial occlusion (IAO) over a 20 year period is presented. Of some 100 patients referred only 28 were found to have IAO and these were critically evaluated in terms of insorptive and exsorptive function. No relation was found between intestinal performance and the degree of potential ischaemia suggested by angiography. Twenty two patients underwent reconstruction of the coeliac axis and mesenteric arteries, with three perioperative deaths. The remainder were followed for periods ranging between six months and 10 years. Of these, 15 are asymptomatic, one is unchanged, and one is subjectively worse. The role of elective surgery in relation to the visceral arteries is critically discussed in the light of these results, and in the perspective of the world experience.

Adult↗
PubMed1985

Cigarette smoke-induced injury of peritoneal mesothelial cells.

Cultured rat peritoneal mesothelial cells have been exposed to plasma obtained from healthy adult male volunteers before and after the smoking of two medium-tar cigarettes. The pre-smoking plasma had little effect on the mesothelial cells as observed by scanning electron microscopy. Post-smoking plasma produced extensive cellular damage evidenced by the production of blebs and microvillus-like structures on the cell surface. Some cells were also found to have a perforated luminal membrane. These results suggest that factors cytotoxic for these cells are present in plasma following exposure of humans to cigarette smoke.

Adult↗
PubMed1984

The mesothelial cell as a non-thrombogenic surface.

A technique for harvesting mesothelial cells is described. This entails collagenase digestion of omentum after which the cells can be cultured. The technique has been developed using the rat, but has also been successfully applied to human tissue. Cultured rat mesothelial cells obtained in this way have been examined by scanning electron microscopy. Rat mesothelial cells grown on plastic film have been exposed to blood in an in vitro system using a Baumgartner chamber and have been demonstrated to support blood flow. No adhering platelets were observed on the mesothelial cell surface. Fibroblasts similarly exposed to blood as a control were washed off the plastic.

Animals↗
PubMed1984

A study of the possible role of mesothelium as a surface for flowing blood.

Mouse mesothelium has been examined as a surface for supporting blood flow. We have examined ten pieces of intact mesothelium and ten pieces of damaged mesothelium following 10 min exposure to flowing blood in a Baumgartner chamber. Scanning electron microscopy of the intact specimens demonstrated no adhering blood platelets, whereas the damaged specimens were found to be covered with large numbers of adhering platelets. In addition we have demonstrated that undamaged mesothelium does not appear to be morphologically altered after exposure to blood, and that undamaged mesothelium produces significantly more prostacyclin than damaged control. These findings support that mesothelial cells hold promise as a lining for prosthetic vascular implants.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Seeding Dacron arterial prostheses with peritoneal mesothelial cells: a preliminary morphological study.

A preliminary laboratory study has been undertaken using dogs, in which porous Dacron arterial prostheses have been seeded with autologous peritoneal mesothelial cells before implantation into the arterial system. These cells were harvested from omentum by collagenase digestion and were introduced into the graft at the time of preclotting. Examination of the grafts by scanning and transmission electron microscopy one month after insertion showed no organized cellular lining in the control graft. In three seeded grafts there was a lining of mesothelial cells which extended over the whole surface of the grafts up to 1 cm from the suture lines. Selected areas of the grafts have been analysed morphometrically. In the seeded grafts there is a cellular layer which on average covers 94 per cent of the luminal surface. These results suggest that mesothelial cells, which both secrete prostacyclin and possess fibrinolytic activity, present a possible alternative to endothelium as a cellular lining for prosthetic grafts.

Animals↗
PubMed1984

Relative potency of prorenoate potassium and spironolactone in attenuating diuretic induced hypokalaemia.

The plasma potassium responses to the aldosterone antagonists prorenoate K (10 mg/day and 40 mg/day) and spironolactone (25 mg/day and 100 mg/day) were compared following treatment for 11 days in combination with the diuretic metolazone (2.5 mg/day) in a double-blind crossover study in twelve healthy men. The best estimate of the potency of prorenoate K relative to spironolactone in attenuating metolazone induced hypokalaemia was 5.6 with 95% confidence limits 2.4-35.2. The method employed allowed a statistically valid quantitative comparison of the potassium sparing properties of the mineralocorticoid antagonists after repeated doses and may be useful in the preclinical evaluation of these drugs.

Adult↗
PubMed1984

Cigarette smoking and platelet adhesion.

Non-abraded rabbit endothelium has been exposed to human blood taken from male non-smoking volunteers before and after the smoking of two medium tar cigarettes, in an in vitro system using a Baumgartner chamber. In each case the blood was allowed to circulate for 10 min at a constant flow rate. Blood from 10 volunteers has been tested in this way. Scanning electron microscopy of the endothelial surfaces demonstrates large numbers of adherent platelets when 'post-smoking blood' is used, but very few and in some cases none with the 'pre-smoking' blood. As a further control to ensure that this phenomenon did not occur as a result from changes in the vessel related to the time during which it had been removed from its normal physiological environment, blood from further non-smoking volunteers was passed over seven of the remaining pieces of vessel at the completion of these runs. Platelets were either absent or very few in number, as with the pre-smoking samples.

Animals↗
PubMed1984

A new instrument for thoracentesis.

Thoracentesis is a commonly performed procedure. Standard techniques have been generally acceptable, but there are occasional serious complications requiring additional treatment and operative procedures. Attempts at near complete aspiration of fluid are often unsuccessful and time consuming with the currently used methods. The change from a sharp needle technique to an intravenous catheter technique has been an improvement, but creates the additional difficulty of briefly exposing the pleural space to atmospheric pressure. Also, blunt end catheters without sideholes may produce incomplete evacuation of fluid, and some intravenous catheters have been cut off and retained in the pleural space. The new instrument described has produced excellent results in a small clinical series. It has effectively overcome the disadvantages of both the standard needle technique and the more current intravenous catheter techniques. The time spent on thoracentesis has been considerably shortened, an advantage for both the patient and the physician alike.

Catheterization↗
PubMed1983

Dose-response relationships for spironolactone in combination with a potassium-wasting diuretic.

The plasma and urine electrolyte responses to repeated doses of spironolactone, 25, 50, and 100 mg, in combination with metolazone, 2.5, 5.0, and 10 mg, were examined in 18 healthy subjects (six at each dose of metolazone). During the period of pharmacologic steady state, there were log linear spironolactone dose-response relationships for plasma potassium, sodium, and bicarbonate (P less than 0.001 in each case) with no contraindication to parallelism between the metolazone groups. In the absence of mineralocorticoid challenge, spironolactone dose-urine electrolyte responses could not be demonstrated. However, after fludrocortisone, spironolactone log dose-response trends were linear with respect to natriuresis (P = 0.027), antikaliuresis (P = 0.020), and log 10 Na/K (P = 0.001), which is usually considered the best single index of renal antimineralocorticoid activity, and exhibited parallelism between the metolazone doses. These observations suggest that a convenient bioassay for aldosterone antagonists in normal men may be provided by the electrolyte responses to repeated doses of such drugs in combination with potassium-wasting diuretics. In view of the limitations of other methods, this approach may have particular relevance to the evaluation of potassium-sparing properties.

Adult↗
PubMed1983

Use of a bioassay in healthy men to evaluate diuretic-spironolactone combinations.

The plasma potassium responses to 1 week's treatment with metolazone 0.625 mg, 1.25 mg and 2.5 mg in combination with spironolactone 50 mg, and metolazone 2.5 alone were examined in a double-blind, crossover study in twelve healthy subjects. Spironolactone attenuated the hypokalaemia induced by metolazone--addition of spironolactone 50 mg to metolazone 2.5 mg raised plasma potassium by 0.18 mmol/l (P less than 0.025). In the presence of spironolactone, a linear log metolazone dose-plasma potassium response relationship (P less than 0.01) was demonstrated. Spironolactone was unable to compensate fully for metolazone's hypokalaemic effect although in combination with metolazone 0.625 mg and 1.25 mg, plasma potassium concentration was maintained close to pretreatment levels. The human bioassay employed provided conveniently quantitative information which allows the rational development of a fixed dose diuretic-spironolactone combination tablet.

Adult↗
PubMed1982

Relative potency and structure activity relationships of aldosterone antagonists in healthy man: correlation with animal experience.

1 The renal antimineralocorticoid potency of single doses of thirteen compounds with properties in animals compatible with competitive aldosterone antagonism was compared to that of spironolactone in healthy men. 2 Twelve compounds showed significant activity when compared to placebo but only one, prorenoate potassium, was significantly more potent than spironolactone on a weight basis. 3 The results allowed ranking of the compounds in order of potency relative to spironolactone and general observations on structure activity relationships in man. 4 Animal bioassays and in vitro aldosterone binding studies are unreliable predictors of the human activity of competitive mineralocorticoid antagonists.

Animals↗
PubMed1981

Bioassay of a new aldosterone antagonist and evaluation of a simple method of quantitative comparison.

The renal antimineralocorticoid activity of single oral doses of a new aldosterone antagonist OH OPC(ME)-K was compared to that of spironolactone in two studies in healthy men. OH OPC(ME)-K reversed the urinary electrolyte response to fludrocortisone in the period up to 16 hr after treatment, but it was less potent than spironolactone on a weight basis. The best estimate of the relative potency of OH OPC(ME)-K: spironolactone (derived from a simple protocol using equal single doses of the two drugs) was 0.60:1 (95% confidence limits 0.24:1 to 1.42:1), in good agreement with the estimate from a more complex three-dose parallel-line bioassay (0.61:1, 95% confidence limits 0.48:1 to 0.79:1). The results of simple single-dose studies can be used, with certain assumptions, to provide a useful estimate of the relative potency of new aldosterone antagonists at an early stage of development.

Double-Blind Method↗
PubMed1980

Activity of sulfur-containing intermediate metabolites of spironolactone.

The renal antimineralocorticoid activity of single administration of 2 sulfur-containing compounds, which are thought to be intermediate metabolites of spironolactone, was assessed in healthy subjects. They were each active in reversing the urinary electrolyte changes indiced by fludrocortisone for 2 to 10 hr after dosing, but only the 7 alpha-thiomethyl derivative exhibited activity in the period 12 to 16 hr after treatment. The activity of both drugs was less than of spironolactone. Taking urinary log 10 Na/K as the best index of antimineralocorticoid activity, the potencies of the intermediates relative to spironolactone were 0.26 (95% confidence limits, 0.12 to 0.49) for 7 alpha-thio-spirolactone and 0.33 (95% confidence limits, 0.15 to 0.62) for 7 alpha-thiomethyl-spirolactone in the period 2 to 10 hr after medication. We conclude that these minor sulfur-containing intermediate metabolites of spironolactone are unlikely to contribute significantly to the renal antimineralocorticoid activity of spironolactone.

Adult↗