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Biomedical subjects

H Wilson

Publications and source records attributed to H Wilson.

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

Structure-activity relationships of arylimidazopyridine cardiotonics: discovery and inotropic activity of 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[4,5-c]pyridine.

Recently several noncatecholamine, nonglycoside cardiotonic drugs have been discovered that possess both inotropic and vasodilator activities in experimental animals and man. Prototypical compounds include amrinone, sulmazole, and fenoximone. We investigated the structural requirements necessary for optimal inotropic activity in a series of molecules containing a heterocyclic ring fused to 2-phenylimidazole and discovered that 2-phenylimidazo[4,5-c]pyridines were generally 5-10-fold more potent than analogous 2-phenylimidazo[4,5-b]pyridines (e.g., sulmazole) or 8-phenylpurines. Furthermore, all imidazo[4,5-c]pyridine analogues we tested were orally active; in contrast, only one of the imidazo[4,5-b]pyridine derivatives, sulmazole, was significantly active. One of several highly active compounds in the [4,5-c] series was 50 (LY175326, 2-[2-methoxy-4-(methylsulfinyl)phenyl]-1H-imidazo[4,5-c]pyridine hydrochloride). The structure-activity relationship of this series is presented and compared to that of the imidazo[4,5-b]pyridine and purine series.

Animals↗
PubMed1985

Antidepressant treatment of children: clinical relapse is unrelated to tricyclic plasma concentrations.

Plasma concentrations of imipramine and amitriptyline and their desmethylated metabolites were measured in 20 children being treated for major depressive illness 2 wk. and 5 to 10 wk. after achieving drug dosages of 2.25 mg/kg body weight. At 2 wk. all children had exhibited clinical improvement, but by 10 wk. 4 of the 10 children treated with imipramine and 5 of the 10 children treated with amitriptyline had experienced clinical relapse of depressive symptoms. Tricyclic antidepressant plasma concentrations and ratios were comparable in the subgroups of children who maintained their clinical improvement and those who relapsed. There was no evidence of a systematic decline in plasma tricyclic antidepressant concentrations in those children who relapsed.

Adolescent↗
PubMed1985

Pharmacology of LY175326: a potent cardiotonic agent with vasodilator activities.

Compound LY175326 is one of a series of novel cardiovascular agents with both inotropic and vasodilator activities. In cat papillary muscles, LY175326 increased contractility in a concentration-dependent manner; these actions were not blocked by prazosin, propranolol or cimetidine. Inotropic responses were observed in unpaced, perfused guinea-pig hearts and these effects were associated with modest increases in heart rate and coronary flow. An i.v. dose of 0.1 mg/kg of LY175326 caused 54 and 95% increases in contractility in either the anesthetized cat or dog, respectively; corresponding heart rates were increased by less than 10%. Oral administration of 0.5 mg/kg to dogs was associated with an inotropic response that was maximal between 60 and 90 min and lasted in excess of 3 hr. These effects were not accompanied by increases in heart rate, gross behavioral changes or emesis. The pharmacology of LY175326 was evaluated in a propranolol-induced heart failure model using anesthetized beagle dogs. A bolus injection of 0.15 mg/kg of LY175326 followed by an infusion of 0.4 mg/kg/hr reversed the hemodynamic symptoms of heart failure by increasing left ventricular dP/dt60, cardiac output and stroke volume and reducing left atrial filling pressure and vascular resistance; heart rate was unchanged and calculated myocardial oxygen consumption was reduced. This balance of inotropic:vasodilator activities may provide a means of improving cardiac function while maintaining the myocardial oxygen supply:demand.

Animals↗
PubMed1984

A word in your ear.

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Community Health Nursing↗
PubMed1984

Amrinone in the treatment of chronic cardiac failure.

The efficacy and safety of oral amrinone were examined in 17 patients with moderately severe to severe heart failure that was refractory to standard medical therapy and vasodilators. The short-term and 28 week response to open amrinone therapy was assessed first, followed by a placebo-controlled, double-blind withdrawal study of two 13 week stages in nine patients. Rest and exercise ventricular function were determined before and after 32 hours of amrinone; aerobic capacity was serially assessed. After 2 hours, 1.64 mg/kg amrinone produced a 40% (p less than 0.001) increase in cardiac output and a 32% (p less than 0.02) decrease in pulmonary wedge pressure without altering heart rate or blood pressure. The exercise cardiac index-wedge pressure curve obtained 32 hours after the first oral dose was significantly shifted (p less than 0.05) above control values. A sustained improvement in maximal oxygen uptake was noted during long-term open amrinone therapy. Subsequently, seven of the patients randomized to placebo therapy had a significant deterioration of symptoms or exercise tolerance, or both. After 4 weeks of readministration of amrinone, clinical stability was once again established and exercise tolerance was improved by Weeks 8 to 16. Adverse effects of thrombocytopenia (one patient) and hepatic dysfunction (one patient) attributable to amrinone were observed. It is concluded that amrinone is effective in the long-term treatment of chronic cardiac failure.

Aged↗
PubMed1984

Jugular foramen syndrome as a complication of metastatic cancer of the prostate.

The jugular foramen syndrome results from paralysis of various combinations of any of the last four cranial nerves. While trauma, vascular disease, and infection may be etiologic, most cases result from malignancies, usually metastatic. We have described a case of metastatic adenocarcinoma of the prostate resulting in the Collet-Sicard variant of this syndrome.

Adenocarcinoma↗
PubMed1983

Generalized primary parathyroid hyperplasia: studies of the evolution of autogenous parathyroid graft function.

The functional evolution of autogenous parathyroid grafts was monitored in six patients with primary parathyroid hyperplasia using a sensitive radioimmunoassay specific for the midregion of parathyroid hormone (PTH). After successful total parathyroidectomy and graft implantation in the forearm, basal immunoreactive PTH (iPTH) fell to undetectable levels for about 12 to 18 weeks, and then rose to normal. By 3 weeks after surgery, an iPTH increment appeared in venous blood from the arm bearing the graft. Graft function was demonstrated in all six cases. Graft-independent hypercalcemia occurred in two patients and appeared to inhibit PTH secretion by the graft. In one case, elevated levels of calcium and iPTH persisted after surgery but iPTH remained equal in both arms. At 5 months, a fifth hyperplastic gland was resected from the mediastinum, and the calcium level decreased to normal; the parathyroid implant was secreting iPTH vigorously 5 days later. Hypercalcemia had not prevented establishment of a viable implant. In the second case, hypercalcemia developed 80 weeks after operation, and the previously demonstrated iPTH gradient disappeared; presumably a fifth gland had become hyperplastic. In this patient, iPTH had remained in the upper portion of the normal range during the first postoperative week, probably indicating the potential for recurrence. Each of the other five patients remains normocalcemic 4 to 103 weeks after grafting.

Calcium↗
PubMed1982

Plasma acid-base patterns in diabetic ketoacidosis.

In a study of the types of plasma acid-base patterns present at 196 admissions for diabetic ketoacidosis we found no relation between the initial level of serum total carbon dioxide and the plasma anion gap; instead, there was a broad spectrum of acid-base patterns, ranging from pure anion-gap acidosis to pure hyperchloremic acidosis. Although the degree of renal dysfunction on admission, which reflected the magnitude of volume depletion, was independent of the severity of metabolic acidosis, it was responsible for the variable retention of plasma ketones: the more severe the volume depletion on admission, the greater the ketone retention and the less prominent the hyperchloremic acidosis. Recovery from acidosis was significantly slower in patients admitted with pure hyperchloremic acidosis. After therapy, hyperchloremia developed in most patients at four to eight hours after admission, because of the retention of chloride in excess of sodium and the excretion of ketones by the kidney.

Acid-Base Equilibrium↗
PubMed1982

Reduplicative paramnesia: a disconnection syndrome of memory.

A case of post-traumatic reduplicative paramnesia (Capgras syndrome) is presented in which the patient experiences duplications in all three spheres of orientation (time, place, person). We postulate that these duplications are the result of a disconnection of new memory registration from past memory stores. The patient is unable to integrate present cues with premorbid experience, and bases judgments of his present orientation upon recollections from the past. A deep lesion at the right posterior hippocampus and temporo-parieto-occipital junction is suggested as the site of this postulated primary memory disconnection, based upon neuropsychological testing and CAT scan results. This right temporal atrophy and memory disconnection appears to have induced immature personality changes.

Adult↗
PubMed1981

Myotonic dystrophy as a disease of abnormal membrane receptors: an hypothesis of pathophysiology and a new approach to treatment.

Muscle weakness, clinical myotonia, and multiple systemic organ disturbances characterize myotonic dystrophy. Many of these systemic disturbances involve target organ insensitivity to aminergic or peptidergic (hormonal) stimulation. Reduced density or impaired function of aminergic and peptidergic (hormonal) receptors throughout the body may underlie this disorder. Tricyclic antidepressant augmentation of aminergic function ameliorates depressive symptoms, increases strength, and improves clinical myotonia in myotonic dystrophy patients.

Antidepressive Agents, Tricyclic↗