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Biomedical subjects

J F Walker

Publications and source records attributed to J F Walker.

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

Acute renal failure and tubular damage due to sepsis in an animal model.

Generalised sepsis was induced in sheep by caecal perforation. Serial measurement of haemodynamic parameters revealed that the subsequent generalised sepsis induced increased cardiac output and decreased systemic resistance comparable to that known to occur in man. Glomerular filtration rate in these animals fell significantly 48 hours after induction of sepsis and there was evidence of tubular damage in the finding of low molecular weight proteinuria and increased clearance of lysozyme. Pathological examination of the kidney revealed normal glomeruli, no consistent changes in tubular cells on light microscopy, negative immunofluorescence, but structural changes in proximal tubular cells on EM. In this model, non-hypotensive sepsis predictably produces damage to proximal tubular cells accompanied by reduction in GFR.

Acute Kidney Injury↗
PubMed1984

Enalapril worldwide experience.

Overall, the worldwide experience on enalapril to date is very encouraging. The drug produces good to excellent responses in 54 to 66 percent of patients with essential hypertension and is at least as effective as either diuretics or beta blockers. The effects of enalapril compared with those of diuretics confirm that patients more dependent upon the renin-angiotensin system respond better. When hydrochlorothiazide is administered concomitantly with enalapril, almost all patients respond, with good long-term maintenance. In patients with severe hypertension, Blocadren or Aldomet may be added in addition to hydrochlorothiazide and will produce additional benefit. Enalapril attenuates the adverse metabolic effects of hydrochlorothiazide, particularly hypokalemia. Overall, although the efficacy of enalapril and that of captopril are similar, enalapril is better tolerated and does not appear to be associated with any significant occurrence of captopril-type side effects, particularly the skin rash and loss of taste. As expected, enalapril and other converting inhibitors may be associated with azotemia in patients with bilateral renovascular hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1984

An overview of the clinical pharmacology of enalapril.

Enalapril maleate is a prodrug which when administered orally is hydrolysed to release the active converting enzyme inhibitor enalaprilat. Enalapril maleate is 60% absorbed and 40% bioavailable as enalaprilat. Both compounds undergo renal excretion without further metabolism. The functional half-life for accumulation of enalaprilat is 11 h, and this is increased in the presence of a reduction in renal function. Inhibition of converting enzyme inhibition is associated with reductions in plasma angiotensin II and plasma aldosterone, and with increases in plasma renin activity and plasma angiotensin I. Acute and chronic effects have been reviewed. When given with hydrochlorothiazide, enalapril attenuates the secondary aldosteronism and ameliorates the hypokalaemia from diuretics. Both acutely and chronically in patients with essential hypertension, enalapril reduced blood pressure with a rather flat dose-response curve. No evidence of a triphasic response such as seen with captopril has been demonstrated with enalapril, and blood pressure returns smoothly to pretreatment levels when the drug is abruptly discontinued. Once- or twice-daily dosing gives similar results. The antihypertensive effects of enalapril are potentiated by hydrochlorothiazide. Haemodynamically, blood pressure reduction is associated with a reduced peripheral vascular resistance and an increase in cardiac output and stroke volume with little change in heart rate. Renal vascular resistance decreases, and renal blood flow may increase without an increase in glomerular filtration in patients with normal renal function. In patients with essential hypertension and glomerular filtration rates below 80 ml/min/m2, both renal blood flow and glomerular filtration rates may increase.

Aldosterone↗
PubMed1984

Tolerance and safety of enalapril.

Enalapril is the result of a targeted research programme to develop a non-mercapto converting enzyme inhibitor with a long duration of action and an improved safety profile for use in the therapy of hypertension and congestive heart failure. Over 3500 patients world-wide have received enalapril or enalaprilat. Long-term experience at present includes over 2500 patients. While enalapril and captopril produce similar efficacy, enalapril is better tolerated and appears not to be associated with occurrence of captopril-type side-effects, particularly the skin rash, taste loss, leukopenia and proteinuria. Enalapril and other converting enzyme inhibitors may be associated with renal insufficiency when given to patients with bilateral renovascular hypertension.

Captopril↗
PubMed1984

Blood--dialyzer interactions: hemodynamic manifestations in an animal model.

A sheep model is described that reliably produces acute pulmonary hypertension after blood, previously in contact with a number of different dialysis membranes including Cuprophan, enters the animal's circulation. This hemodynamic manifestation is associated with myocardial ischemia and arrhythmias and coincides in time with neutropenia but precedes maximal hypoxemia. The resulting pulmonary vascular response occurs following both exposure of flowing blood to a dialyzer in an extracorporeal circuit and reinjection of blood previously in static contact with a number of different devices for varying periods of time. Increasing volumes (1-15 ml) previously in static contact (10 min) with regenerated cellulose, saponified cellulose ester, and Cuprophan (hollow fiber and sheet form) caused varying increments in mean pulmonary artery pressure. Contact with either polyacrylonitrile or cellulose acetate resulted in little response. This effect was magnified with all the surfaces, even polyacrylonitrile and cellulose acetate, by prolonging the duration of contact up to 30 min. The hemodynamic events that occurred with this model are similar to those reported in the clinical entity of "dialyzer hypersensitivity." This model may be of value in the quest for elucidation of the mechanisms involved in this syndrome.

Acrylic Resins↗
PubMed1984

The efficacy and safety of enalapril in moderate to severe essential hypertension.

When added to hydrochlorothiazide, enalapril is as effective as captopril in the treatment of moderate to severe hypertension. It is also effective when used as monotherapy, and may be incorporated into a regimen with diuretic and methyldopa or timolol for the treatment of more resistant patients. Enalapril has a good safety profile as measured by frequency of clinical and laboratory adverse experiences.

Adult↗
PubMed1984

Overall tolerance and safety of enalapril.

To date, more than 5000 patients have had experience with enalapril. Over 1000 subjects have been exposed to the drug for more than one year and approximately 600 for over two years. In controlled trials, 2249 subjects, who included normal volunteers and patients with hypertension and congestive heart failure, have received enalapril alone or concomitantly with hydrochlorothiazide or other antihypertensive agents. There have been no deaths attributed to enalapril. The incidence of serious adverse experiences in controlled trials was similar to placebo, and was not higher in the elderly. The incidence of adverse experiences was not dose-related. Drug discontinuation due to adverse experiences was 3.5%, similar to placebo, and approximately half that of control drugs. Serious laboratory adverse experiences were rare. Enalapril attenuated the adverse metabolic effects of hydrochlorothiazide, particularly hypokalaemia. Skin rash occurred in approximately 1.0% of patients. One case of transient taste loss occurred on enalapril, and one on enalapril in combination with hydrochlorothiazide. Neutropenia and agranulocytosis were not encountered. Mean white blood cell counts did not change overall. Most patients (approximately equal to 80%) show no change or an improvement in renal function on enalapril. Discontinuation of concomitant hydrochlorothiazide usually normalized renal function. Enalapril is well tolerated in renal insufficiency. Azotaemia may occur in bilateral renovascular hypertension. Proteinuria was rarely seen and often improved on enalapril. Compassionate use protocols have been available to patients either resistant or intolerant to captopril. Of 68 patients admitted for captopril-related skin rashes, only five recurred on enalapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗
PubMed1983

Enalapril in low-renin essential hypertension.

The antihypertensive efficacy of N-[(S)-1-(ethoxycarbonyl)-3-phenyl-propyl]-L-alanyl-L-proline (enalapril maleate) was evaluated in a randomized, double-blind trial in 23 patients with mild low-renin essential hypertension ranging in age from 32 to 70 yr (20 were black and 3 were white). All underwent a 4-wk washout-placebo phase and were then assigned to a dosing schedule of either 10 mg enalapril once daily, 5 mg enalapril twice daily, or placebo twice daily for 12 wk. Conditional on diastolic pressure, the dose was increased at 4-wk intervals to a maximum of 40 mg daily or until control was achieved or the end of the study reached. At the end of the 12-wk titration phase, there was a follow-up period during which measurements were made after discontinuation of the medication. Mean supine diastolic pressure decreased from baseline (98.5 +/- 2.6 mm Hg) during the titration phase (86.3 +/- 4.6 mm Hg) in the group taking enalapril once daily. In three of the eight patients in the once-daily group and five of eight in the twice-daily group, supine diastolic pressures fell below 90 mm Hg. Neither supine nor standing systolic pressure nor standing diastolic pressure decreased significantly from pretreatment levels during enalapril once or twice daily. Heart rates measured after 5 min supine rest were not altered by enalapril. Enalapril induced inhibition of converting enzyme activity at all dose levels and with both dosing schedules. No adverse effect attributable to enalapril occurred during the study. The data indicate that once-daily enalapril is safe and effective treatment for mild low-renin essential hypertension.

Adult↗
PubMed1983

Immunoreactive bradykinin and [des-Arg9]-bradykinin in low-renin essential hypertension--before and after treatment with enalapril (MK 421).

Bradykinin (BK) and [des-Arg9]-bradykinin (-9BK) concentrations in blood and urine samples from 18 normotensive subjects and 23 patients with low-renin essential hypertension were determined by radioimmunoassay. BK and -9BK levels in venous blood from normotensive subjects were 67.1 +/- 60.8 pg/ml and 204.1 +/- 44.5 (mean +/- S.D.), respectively, and levels in urine from normotensive subjects were 5.3 +/- 5.3 ng/ml and 1.6 +/- 1.2, respectively. The blood and urinary levels of BK and -9BK in low-renin essential hypertensives were not significantly different from those of normotensives and did not change when the hypertensives were treated with the new orally active angiotensin I-converting enzyme (ACE) inhibitor, enalapril (MK421). It has been proposed that BK levels do not change with ACE inhibition because under these conditions BK might be metabolized to -9BK by kininase I. Since -9BK levels did not increase with MK421 treatment, this possibility can be excluded. The absence of elevations in blood and urine BK and -9BK after administration of MK421 does not support an involvement of kinins in the mechanism of antihypertensive action of MK421 in these patients. On the basis of the data, it is not possible to exclude such an involvement, however, because local changes in kinin concentrations could occur that are not reflected by changes in circulating or urinary kinin levels.

Adult↗
PubMed1983

IgA nephritis with nephrotic range proteinuria.

Nephrotic range proteinuria is uncommon in patients with IgA nephritis. For this reason we compared the clinical and pathologic features in 63 non-nephrotic patients with those in 8 patients who had nephrotic range proteinuria at the time of biopsy. Both the mean age and the mean duration of the disease at the time of diagnosis were not significantly different in the 2 groups of cases. Significant associations were found between nephrotic range proteinuria and the following: the extent of glomerular hyalinization, the severity of interstitial fibrosis and tubular atrophy and the degree of foot process effacement and mesangial matrix increase. A significant association was also noted with nephrotic range proteinuria had elevated levels of serum creatinine on follow-up compared with 20% of non-nephrotic cases. The results of our study suggest that patients with nephrotic range proteinuria have a more severe type of IgA nephritis from the outset and that a marked degree of proteinuria is not merely a consequence of the duration of disease.

Adult↗