Search PubMed⌕ Search

Biomedical subjects

J W Ward

Publications and source records attributed to J W Ward.

At least 109 records · Page 6Linked to original sources
PubMed1985

Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin.

We studied the pharmacokinetics and beta-blocking effects of a single, oral 20 mg dose of timolol in six poor metabolizers (PMs) and six extensive metabolizers (EMs) of debrisoquin. The plasma timolol concentration was significantly higher in PMs than in EMs. There was a fourfold difference in mean AUC (1590 +/- 1133 vs. 394 +/- 239 ng X hr/ml; P less than 0.01) and a twofold difference in mean t1/2 (7.5 +/- 3 vs. 3.7 +/- 1.7 hours; P less than 0.01), reflecting differences in oral clearance (13.1 +/- 7.8 vs. 48.5 +/- 23.2 L/hr; P less than 0.01). The degree of beta-blockade was greater in PMs than in EMs at 12 hours (30.9% vs. 18.2%; P less than 0.05) and at 24 hours (28.3% vs. 13.1%; P less than 0.05). In the group as a whole the metabolic ratio correlated positively with both kinetic data and beta-blockade, but some overlap was observed. Hence timolol metabolism appears to be subject to debrisoquin-type polymorphism, which results in interphenotypic variation in plasma concentration and beta-blocking effect.

Absorption↗
PubMed1985

The superficial musculoaponeurotic system in the upper lip: an anatomic study in cadavers.

Ten cadavers were employed to demonstrate the presence of the SMAS in the upper lip using macroscopic and microscopic techniques. The relationships and attachments of the SMAS to the dermis of the upper lip are described. In cadavers, medial traction on the SMAS in the upper lip in conjunction with superolateral traction on the SMAS in the cheek is found to decrease the depth of the nasolabial fold. Superior traction on the SMAS in the upper lip elevates the interlabial line, reestablishes the convexity of the lateral vermilion border, and partially increases concavity of the profile.

Adult↗
PubMed1985

Pollicization for thumb reconstruction in severe pediatric hand burns.

Our experience in pollicization of the index ray for severely burned hands in children is reviewed with attention to severity of burn, functional impairment, age at pollicization, procedure used, operative time, length of hospital stay, and long-term functional results. Fifteen pollicizations were performed in 11 patients with an average follow-up of over 5 years. Indication for pollicization was lack of prehension due to total loss of the thumb with the presence of a transposable index ray. The bipedicle flap method was used in two cases and the neurovascular pedicle technique was employed in all others. Skin grafts were necessary in all cases. Results were graded according to presence or absence of tip pinch, key pinch, grasp, and opposition. Significant functional improvement was seen in 14 of 15 cases (94 percent). Four patients (27 percent) developed complications requiring secondary procedures. In our experience, pollicization provides the most rapid and effective means of restoration of thumb function in the severe pediatric hand burn with multiple digit loss.

Adolescent↗
PubMed1985

Serum concentrations and urinary excretion of pinacidil and its major metabolite, pinacidil pyridine-N-oxide following i.v. and oral administration in healthy volunteers.

Serum concentrations of pinacidil and its major metabolite pinacidil pyridine-N-oxide were determined following administration of both an intravenous solution and a sustained release oral preparation to healthy volunteers. Mean bioavailability of pinacidil was 57.1 +/- 13.7%. Following intravenous administration, the mean AUC0-8 h metabolite/AUC 0-8 h pinacidil ratio was 0.559 +/- 0.272 and after oral administration, 0.825 +/- 0.656. Only one subject had serum metabolite concentrations in excess of pinacidil during the intravenous study whereas three subjects achieved metabolite concentrations in excess of pinacidil during the oral study. The mean serum elimination half-life of metabolite was significantly longer than parent drug following intravenous administration (P less than 0.01) but not after oral administration. No significant difference was found in the maximum measured metabolite concentration (Cmax.m) between the studies. The time to Cmax.m was significantly delayed (P less than 0.001) following oral dosage. Twenty four hour urinary excretion of metabolite was significantly increased (P less than 0.001) following oral administration whilst that of pinacidil was decreased (P less than 0.02). These results suggest that pinacidil pyridine-N-oxide may be a 'first-pass' metabolite of pinacidil. In most patients pinacidil pyridine-N-oxide is unlikely to contribute significantly to the hypotensive effect of pinacidil.

Administration, Oral↗
PubMed1985

Inhibition of platelet function in thrombosis.

Accumulating experimental and clinical evidence indicates that a time for reappraisal of therapeutic modalities designed to inhibit the eicosanoid pathway as it may affect vascular disease may be approaching. Pharmacologic agents originally used were chosen because they were capable of suppressing platelet functions such as aggregation, release, and adhesion. The goals of clinical trials were to evaluate medications that would prevent or reduce platelet accumulation in critically located blood vessels of the heart, brain, and extremities and on vascular prostheses. Evaluation of results of therapeutic trials has been difficult and this is superimposed on less-than-complete knowledge of the basic pharmacology of the drugs that have been used. Participation of neutrophils and possibly macrophages in the thrombotic process is now well recognized on morphologic grounds. Because different cell types such as platelets, neutrophils, and endothelial cells have been shown to interact biochemically by sharing precursors and intermediates of the eicosanoid pathway, the pharmacologic approach to inhibition of vascular disease may require reevaluation. Neutrophils appear to lack a cyclooxygenase pathway but serve as a source of the lipoxygenase product leukotriene B4 (LTB4). Actions of LTB4 include neutrophil aggregation, adhesion of neutrophils to endothelial cells, chemotaxis, chemokinesis, and plasma exudation. We have demonstrated in vitro that released free arachidonic acid from aspirin-treated platelets can serve as a source of neutrophil LTB4. Leukotrienes C4, D4, and E4 are agonists for various functions of vascular endothelium and smooth muscle. Most pharmacologic agents used in the treatment of vascular diseases inhibit the cyclooxygenase pathway.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acids↗
PubMed1984

Pharmacokinetics and hypotensive effect in healthy volunteers of pinacidil, a new potent vasodilator.

Preliminary investigation in 3 healthy volunteers suggested that intravenous pinacidil in a dose of 0.2 mg/kg had a potent but well-tolerated hypotensive action in the supine position. Facial flushing, uncomfortable chest sensation and distressing postural hypotension occurred at serum concentrations above 300 ng/ml. Pinacidil, 0.2 mg/kg, was given intravenously over 4 min to 15 healthy volunteers in the supine position. Maximum fall in mean arterial pressure (MAP) was 15.7 +/- 6.0 mmHg. Maximum rise in heart rate was 23.8 +/- 6.6 beats/min. Pinacidil serum distribution half-life (T1/2 alpha) was 13.4 +/- 8.5 min and elimination half-life (T1/2 beta) was 2.13 +/- 0.49 h. The apparent volume of distribution (Vd beta) was 90.3 +/- 13.21 and total body clearance was 31.1 +/- 9.61/h. Pinacidil was approximately 40% bound to plasma protein over the concentration range 40-400 ng/ml. Urinary excretion of unchanged pinacidil accounted for 5.7 +/- 1.3% of the administered dose over 24 hours and urinary excretion of the major metabolite, pinacidil pyridine-N-oxide, was 31.6 +/- 9.2% of the administered dose. It was concluded that intravenous pinacidil is a potent vasodilator hypotensive compound, with a duration of action between 1.5 and 2 h.

Adult↗
PubMed1984

Irritative properties of two clinical potassium chloride formulations on duodenal mucosa of the cat and esophageal mucosa of the opossum.

The local gastrointestinal irritating properties of microencapsulated KCl (M-E), a new and unique form of KCl (8 meq potassium per capsule), were compared with a wax-matrix (W-M) KCl formulation (8 meq potassium per tablet). Normal saline in 0-size gelatin capsules was used as the control substance. The comparisons were made in two animal models that simulate the condition of partial obstruction of the gastrointestinal tract in humans. These models are the duodenum of the cat and the esophagus of the opossum, each with a surgically created partial obstruction. The tissues were exposed to two capsules or tablets of KCl or saline for 4 hr, and the extent of tissue injury assessed by using a rating scale. The irritation caused by M-E was significantly (P less than 0.05) less than that caused by W-M in both the cat and the opossum, and it was not significantly (P greater than 0.05) different from the injury caused by saline in either model. The relative lack of irritation by M-E is probably explained by the fact that there was a significantly (P less than 0.05) greater dispersion of KCl from the M-E capsule than from the W-M tablet.

Animals↗
PubMed1984

Pinacidil monotherapy for hypertension.

Ten patients with mild to moderate hypertension were treated for 9 weeks with a tablet formulation of pinacidil. Mean supine blood pressure fell from 174/100 to 148/84 mm Hg and mean supine pulse increased by 3 beats/min. Daily dosage was 40-100 mg, given in two or three divided doses. Plasma urea increased significantly and mean weight increased by 1.1 kg. Side effects were frequent but mild, in the main being those typically associated with potent vasodilator drugs. No patient withdrew from the study, and all achieved target blood pressure.

Adult↗
PubMed1984

Absorption of lignocaine and bupivacaine from the respiratory tract during fibreoptic bronchoscopy.

Absorption of lignocaine and bupivacaine from the upper and lower respiratory tract was studied in patients undergoing fibreoptic bronchoscopy. No significant differences were found between the drugs and between the routes of administration in terms of the time taken to achieve maximum plasma concentrations. The relative availability of lignocaine was greater following administration via the upper respiratory tract, but bupivacaine availability did not differ. The apparent clearance of lignocaine was not affected by the route of administration but bupivacaine clearance was higher following administration via the lower respiratory tract. Bupivacaine, previously unreported as a topical agent in man, produced adequate anaesthesia at one-eighth of the dose of lignocaine. Plasma bupivacaine concentrations had a very wide safety margin.

Absorption↗
PubMed1984

Fatal self-poisoning with benoxaprofen.

A report of the first fatal self-poisoning due to primary toxicity of benoxaprofen. Benoxaprofen is toxic in acute overdosage to the central nervous system, myocardium and kidneys, but appears to spare the liver.

Anti-Inflammatory Agents↗
PubMed1983

Prediction of Wiggins content scale scores from 168- and 399-item abbreviations of the MMPI.

Multiple regression equations for estimating Wiggins content scores from 399- and 168-item abbreviations of Form R of the Minnesota Multiphasic Personality Inventory (MMPI) were derived for 100 patients and cross-validated in a separate sample of 50 patients. Across samples, Rs between 399-item short form scales and corresponding full scales were very high (median = .98 for the total sample), and the equations predicted accurately in cross-validation. Rs in estimating from 168 items were lower (median = .91 for the total sample), but the equations estimated mean content scores well in cross-validation. These results were viewed as indicating that there may be little loss in estimating from 399 items but that error in prediction may be unacceptably high for some of the 168-item short form scales. The correspondence of Wiggins scales and standard MMPI scales was also studied through regression analyses, and it was concluded that, although there is considerably overlap in the two sets of scales, inferences as to self-report content from the standard scales are not always simple or especially accurate.

Adult↗
PubMed1982

Identification and labeling of EEG graphic elements using autoregressive spectral estimates.

Syntactic EEG analysis requires descriptive labeling of short (1 s) epochs in an EEG. While discriminant analysis methods are useful for this purpose, significant improvement in label correctness can be achieved using the heuristic method described in this paper. The method is based on the estimation of frequency spectra by autoregressive (AR) modeling. The location of the peak frequencies and the power of these peaks are used to assign labels to 1 s epochs. Artefacts and epochs with exceptionally high or low amplitude and/or frequency values are identified as well. The assignment of labels is accomplished by comparing parameters, extracted from the power spectra estimated for 1 s epochs, with thresholds. These thresholds are automatically adapted to each individual EEG lead. In this paper, the method is outlined and its performance is compared with a discriminant analysis approach and visual labeling.

Computers↗