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Biomedical subjects

J L Anderson

Publications and source records attributed to J L Anderson.

At least 289 records · Page 16Linked to original sources

The "on-off" phenomenon in Parkinson's disease. Relation to levodopa absorption and transport.

To determine whether the oscillating clinical response to levodopa in Parkinson's disease (the "on-off" phenomenon) reflects fluctuations in absorption and transport of the drug, we investigated this phenomenon in nine patients with an oscillating motor state. We studied the response to continuous infusion of levodopa and the effects of meals on the plasma levodopa concentrations and on the clinical response during oral and intravenous administration of the drug. Meals reduced peak plasma levodopa concentrations by 29 per cent and delayed absorption by 34 minutes. Bypassing absorption by constant infusion of the drug produced a stable clinical state lasting for 12 hours in all of six patients and for up to 36 hours in some. High-protein meals or oral phenylalanine, leucine, or isoleucine (100 mg per kilogram of body weight) reversed the therapeutic effect of infused levodopa without reducing plasma levodopa concentrations. Glycine and lysine at identical doses had no effect. We conclude that interference with absorption of levodopa by food and by competition between large neutral amino acids and levodopa for transport from plasma to the brain may be partly responsible for the fluctuating clinical response in patients with Parkinson's disease.

Administration, Oral↗

Clinical use of the total artificial heart.

We report here our first experience with the use of a total artificial heart in a human being. The heart was developed at the University of Utah, and the patient was a 61-year-old man with chronic congestive heart failure due to primary cardiomyopathy, who also had chronic obstructive pulmonary disease. Except for dysfunction of the prosthetic mitral valve, which required replacement of the left-heart prosthesis on the 13th postoperative day, the artificial heart functioned well for the entire postoperative course of 112 days. The mean blood pressure was 84 +/- 8 mm Hg, and cardiac output was generally maintained at 6.7 +/- 0.8 liters per minute for the right heart and 7.5 +/- 0.8 for the left, resulting in postoperative diuresis and relief of congestive failure. The postoperative course was complicated by recurrent pulmonary insufficiency, several episodes of acute renal failure, episodes of fever of unidentified cause (necessitating multiple courses of antibiotics), hemorrhagic complications of anticoagulation, and one generalized seizure of uncertain cause. On the 92nd postoperative day, the patient had diarrhea and vomiting, leading to aspiration pneumonia and sepsis. Death occurred on the 112th day, preceded by progressive renal failure and refractory hypotension, despite maintenance of cardiac output. Autopsy revealed extensive pseudomembranous colitis, acute tubular necrosis, peritoneal and pleural effusion, centrilobular emphysema, and chronic bronchitis with fibrosis and bronchiectasis. The artificial heart system was intact and uninvolved by thrombosis or infectious processes. This experience should encourage further clinical trials with the artificial heart, but we emphasize that the procedure is still highly experimental. Further experience, development, and discussion will be required before more general application of the device can be recommended.

Blood Pressure↗

Pirmenol for control of ventricular arrhythmias: oral dose-ranging and short-term maintenance study.

The antiarrhythmic efficacy and safety of oral pirmenol hydrochloride were assessed during a controlled, dose-ranging and short-term maintenance study in 12 patients with frequent (greater than 480/8 hours) premature ventricular complexes (PVCs). Eleven patients (92%) responded favorably (greater than 70% PVC suppression) to a trial of different doses. Mean interval (8-hour) suppression of PVC frequency was 95% in these 11 and 86% in the entire group. Twenty-four-hour suppression was similar in responders (88%). Repetitive PVCs were essentially eliminated. The mean effective dose was 316 mg/day (105 mg/8 hours). The average predose (trough) plasma concentration at the end of dose ranging was 1.4 micrograms/ml and the drug elimination half-life 7.3 hours (n = 12). Of 11 responding patients, 10 completed a 2-week outpatient trial. Pirmenol continued to be effective and tolerated in 8 patients, maintaining an overall average outpatient PVC suppression of 80%. The electrocardiographic intervals were mildly prolonged after multiple dosing (PR + 7%, QRS + 12%, QTc + 8%; all p less than 0.01). Blood pressure and heart rate did not change during treatment. The echocardiographic ejection fraction was maintained. Thus, oral pirmenol appears to be effective, conveniently administered and well tolerated as an antiarrhythmic agent for control of ventricular extrasystoles.

Administration, Oral↗

Comparative effects of diltiazem, propranolol, and placebo on exercise performance using radionuclide ventriculography in patients with symptomatic coronary artery disease: results of a double-blind, randomized, crossover study.

The effects of oral diltiazem (120 mg), propranolol (100 mg), and placebo on exercise performance and left ventricular function were compared before and during symptom-limited supine bicycle exercise by means of multigated radionuclide ventriculography in 12 patients with documented, symptomatic coronary artery disease; a double-blind, randomized crossover protocol was used. Diltiazem increased ejection fraction (EF) at submaximal exercise (+7.0 absolute percentage points, p less than 0.02) and maximal exercise (+8.1 percentage points, p less than 0.01). Exercise EF was increased by 13.6 percentage points (p less than 0.02) in patients with decreased ventricular function (resting EF less than 50%). Propranolol had no effect on exercise EF at any stage, even when patients with EF less than 50% were excluded. The increase in total exercise time was significant after diltiazem (+27%, p less than 0.01) but not after propranolol (+16%, p = NS). As expected, propranolol decreased both resting (-9 bpm, p less than 0.01) and exercise heart rates (-27 bpm, p less than 0.001), whereas diltiazem had no significant effect. Propranolol decreased resting diastolic blood pressure (-8 mm Hg, p less than 0.02), exercise systolic (-27 mm Hg, p less than 0.001) and diastolic (-9 mm Hg, p less than 0.01) blood pressures, and rest (p less than 0.01) and exercise (p less than 0.001) double product. Diltiazem decreased resting systolic blood pressure (-9 mm Hg, p less than 0.01) and both resting (-8 mm Hg, p less than 0.001) and exercise (-9 mm Hg, p less than 0.01) diastolic blood pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Long-term follow-up after intracoronary streptokinase for myocardial infarction: a randomized, controlled study.

Intracoronary streptokinase (SK) may have beneficial effects on the in-hospital course of acute myocardial infarction (MI), but long-term outcome is unknown. We evaluated the outpatient course of 50 MI patients, randomly treated with either SK (n = 24) or standard therapy (n = 26), who presented within 2.7 +/- 0.7 hours of symptoms. Coronary reperfusion occurred in 19 (79%) SK patients. Survivors were followed for a mean of 18.7 months (range 11 to 28.5); information was current in 48 patients (96%). Both groups received antiplatelet therapy for 3 months. A total of five deaths occurred in the control group and two in the SK group, including one posthospital death in each. Nonfatal MIs totaled five in control patients and three in SK patients, including five posthospital MIs (three control, one SK). Differences in major events (death or nonfatal MI) favoring SK did not quite reach statistical significance (10 control vs 5 SK). Bypass surgery was performed in seven SK and four control patients (NS). Angina occurred in more control (15) than SK (six) patients (p less than 0.01), and more control patients used long-acting nitrates (14 control, three SK; p less than 0.01). Palpitations were noted by nine control and one SK patient (p less than 0.01), and documented late arrhythmias were present in four control patients and no SK survivors (p less than 0.05). Symptoms suggestive of heart failure were present in seven control and one SK patient (p less than 0.01); two control patients were hospitalized for failure. Use of beta blockers, calcium channel blockers, and other cardiac medications did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Quercetin: a mutagen, not a carcinogen, in Fischer rats.

Purified quercetin, as well as diets containing quercetin at 0.1% and 0.2%, are mutagens to Salmonella typhimurium TA100. This mutagenicity is enhanced with the S9 metabolic activation system. The urine of Fischer rats fed the 0.2% quercetin diet also is mutagenic with the S9 activation system, but the feces of these animals exhibited enhanced mutagenicity only without activation. This may indicate different quercetin metabolites in urine and feces. Rats fed these diets for 64 wk showed no consistent tissue lesions, carcinogenicity, or reproductive changes. Male rats fed 0.2% quercetin showed lowered blood serum glutamic oxaloacetic transaminase and urea nitrogen levels, but these values do not reflect pathological changes.

Animals↗

Toxicologic studies with male sheep grazing on municipal sludge-amended soil.

Growing sheep were grazed for 152 d on grass-legume forage growing on soil that had been amended with municipal sewage sludge from Syracuse, N.Y., at 224 metric tons per hectare. Cadmium was higher, but not significantly (p greater than 0.05), in tissues of sheep fed the sludge-grown forage as compared to controls. No significant differences between the sludge or control treatments were found in weight of the complete or cauda epididymis or in percent progressive motility of cauda epididymal sperm. The sludge-treatment group had significantly larger testes (p less than 0.025) when expressed as a percentage of body weight, and higher blood uric acid values (p less than 0.05). There were no observable changes in tissue ultrastructure of liver, kidney, muscle, or testes as examined by electron microscopy in either of the treatment groups. There were no significant differences for rate of animal weight gain, carcass weight, dressing percentage, or quality or yield grade of the carcases between the treatment groups.

Animals↗

A randomized trial of intravenous and intracoronary streptokinase in patients with acute myocardial infarction.

The clinical effects of intravenous streptokinase in patients with acute myocardial infarction were compared with those of intracoronary streptokinase in a randomized, prospective study. Comparisons were also made with a historical control group. Fifty patients were entered into the study at 2.4 +/- 1.2 hr after onset of pain, and 27 were assigned to intravenous and 23 to intracoronary therapy. The doses of streptokinase averaged 212,000 U ic and 845,000 U iv (0.75 X 10(6) U/5 hr, n = 14 or 10(6) U/1 hr, n = 13). Results of studies of the two intravenous dosage schedules were similar and so were combined. Streptokinase was administered at 2.8 +/- 1.0 hr after onset of pain in the intravenous and at 4.3 +/- 1.4 hr in the intracoronary drug group (p less than .001). Convalescent (day 10) radionuclide ejection fractions were 54 +/- 14% for the intravenous and 50 +/- 16% for the intracoronary drug group. Change in ejection fraction from day 1 to 10 tended to be greater after intravenous drug: 5.1% (p less than .08) vs 1.2% (NS). Semiquantitative regional wall motion indexes in the infarct zone showed significant and similar modest improvement from admission to day 10 in both groups (p less than .02). Accelerated enzyme-release kinetics were noted after both therapies. Times of peak enzyme levels for patients on intravenous and intracoronary drug were, respectively, 12.5 +/- 5.0 and 11.5 +/- 4.3 hr for creatine kinase MB isoenzyme and 31.7 +/- 11.8 and 28.1 +/- 12.7 hr for lactic dehydrogenase (LDH). Peak LDH-1 level was lower in patients receiving intravenous drug than in the historical control group (p less than .05). Electrocardiographically summed ST segments diminished rapidly after therapy in both groups; Q wave development was similar and overall R wave loss was equivalent and less extensive compared with in historical control subjects. Infarct pain requiring morphine was diminished similarly in both treatment groups. Incidence of early arrhythmias and heart failure also did not differ. Posttherapy ischemic events and early surgery tended to be more common in the intracoronary group and bleeding was more common in the intravenous group. Intravenous drug did not decrease early hospital mortality (intravenous drug = 5, historical control = 4, intracoronary drug = 1); the differences in this parameter among groups were not significant. At convalescent angiographic evaluation, anterograde perfusion was present in 73% of those receiving intravenous and 76% of those receiving intracoronary drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Description of an undergraduate sterile products clerkship.

A description of a ten week, full-time, elective sterile products clerkship designed for fifth year pharmacy students is presented. The course refines the student's written and oral communication skills and meets the NCCLVP standard for education of IV therapy personnel.

Clinical Clerkship↗

Current understanding of lidocaine as an antiarrhythmic agent: a review.

Lidocaine generally is the agent of first choice against acute ventricular arrhythmias arising from many causes. It is clinically effective and well tolerated, having a rapid onset of action and a favorable electrophysiological profile. Unlike other antiarrhythmic agents, lidocaine does not interact with the autonomic nervous system. A review of the literature highlights current knowledge about this antiarrhythmic drug.

Age Factors↗

A randomized trial of intracoronary streptokinase in the treatment of acute myocardial infarction.

Fifty patients with acute myocardial infarction were randomly assigned to receive either intracoronary streptokinase or standard (control) therapy within about three hours after the onset of pain. Coronary perfusion was reestablished in 19 of 24 patients receiving streptokinase. Streptokinase alleviated pain (as indicated by differences in subsequent morphine use). The Killip class was significantly improved after therapy with streptokinase, as were changes in radionuclide ejection fraction between Days 1 and 10 in surviving patients (+3.9 vs. -3.0 per cent, P less than 0.01). The echocardiographic wall-motion index also showed greater improvement after streptokinase treatment (P less than 0.01). Streptokinase therapy was associated with rapid evolution of electrocardiographic changes, which were essentially complete within three hours after therapy, but loss of R waves, ST elevation, and development of Q waves in the convalescent period were greater in the control group (P less than 0.01). The time required to reach peak plasma enzyme concentrations was significantly shorter after streptokinase. The incidence of early and late ventricular arrhythmias was not affected by treatment. We conclude that intracoronary streptokinase appears to have a beneficial effect on the early course of acute myocardial infarction.

Adult↗

Serotonin receptor changes after chronic antidepressant treatments: ligand binding, electrophysiological, and behavioral studies.

Early biochemical research on antidepressant treatments provided evidence that the treatments alter catecholaminergic and serotonergic activity. The mechanisms of action proposed by the resulting biogenic amine hypotheses of affective disorders, however, are not consistent with the delayed onset of therapeutic effects of antidepressant treatments nor with the acute effects of more recently developed antidepressant drugs. Recent investigation of chronic antidepressant treatments using ligand binding, electrophysiological, and behavioral techniques have attempted to identify subgroups of receptors that might be affected uniquely and specifically by chronic antidepressant treatments. Such receptor changes have been suggested to form a basis for the mechanism of action of antidepressants. At the present time, however, the data produced by ligand binding experiments and electrophysiological experiments investigating serotonergic functioning do not fit together. In addition, interpretational problems and internal contradictions exist within each of the three bodies of data when straightforward hypotheses regarding a serotonergic role in antidepressant treatment are formulated. In order to clarify the serotonergic role in antidepressant drug and ECS effects the functional significance of observed changes in putative serotonergic receptors must be discovered. Unfortunately, putative receptors identified by ligand binding cannot be directly compared to those identified by electrophysiological techniques, because these two methods require the disassembly of the organism in mutually incompatible ways. In order to prove that either or both techniques do in fact identify functional serotonin receptors, investigators need to proceed both more microscopically and also more globally. Further anatomical and physiological studies are necessary to locate putative receptors and to demonstrate their place in existing serotonergic networks. Further behavioral studies must be done to relate alterations in receptor characteristics to the functioning of the intact organism.

Animals↗

Solute concentration effect on osmotic reflection coefficient.

A theory for the effect of concentration on osmotic reflection coefficient, correct to first order, was developed at the molecular level by considering the effect of solute-solute interactions on solute concentration and the fluid stress tensor within a solvent-filled pore. The solvent was modeled as a continuous fluid and potential energies between solute molecules and the pore wall were assumed to be pairwise additive. Although the theory is more general, calculations are presented only for excluded volume effects (hard-sphere for solute, hard-wall for pore). The relationship between the first-order concentration effect and the infinite dilution value of reflection coefficient appears to be geometry independent. The theory is discussed in light of experimental studies of osmotic flow that have recently appeared in the literature.

Mathematics↗