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Biomedical subjects

W Woodward

Publications and source records attributed to W Woodward.

At least 19 recordsLinked to original sources
PubMed1995

Dose- and duration-dependent tolerance to rotational effects of apomorphine in a rat model of Parkinsonism.

We sought to determine what temporal and dose factors influence the development of tolerance to dopaminergic agents in parkinsonism. Apomorphine was administered at varying doses and durations to rats with unilateral 6-hydroxydopamine-induced nigrostriatal lesions and rotational behavior was monitored. Ten rats were studied across seven daily, intermittent treatment sessions, during which four equal boluses of apomorphine were injected at 1- to 2-hr intervals; increasing doses were used on different days. The total number of rotations were reduced by approximately 25% after repeated 0.8- and 3.2-mg/kg doses, but not after doses ranging from 0.1 to 0.4 mg/kg; neither the peak rate nor the duration of responses were altered. Nine other, untreated rats received four, 0.8-mg/kg boluses of apomorphine and did not exhibit any decrement in response. An 8-hr constant treatment (0.2-mg/kg boluses every 10 min) resulted in a 70% reduction in rotational response; plasma levels remained stable in five unlesioned rats who underwent a similar constant treatment. These results suggest that tolerance to dopaminergic stimulation is more apt to develop with constant than with intermittent treatment and that tolerance may require previous drug exposure in order to occur. Optimal treatment of patients with severe parkinsonism may require periods without dopaminergic effect in order to maintain drug response.

Animals↗
PubMed1992

3-O-methyldopa administration does not alter fluorodopa transport into the brain.

To determine if 3-O-methyldopa (3OMD) significantly inhibits the transport of 6-[18F]fluorodopa (6-FD) into the brain at the concentration normally encountered during L-dopa administration, we performed 6-FD studies with positron emission tomography in cynomolgus monkeys in the presence and absence of 3OMD. Infusion of 3OMD was designed to produce plasma concentrations equivalent to those seen in patients on chronic L-dopa therapy. Plasma 3OMD levels of 39 +/- 4 microM did not alter the blood-brain transfer rate of 6-FD. 6-FD positron emission tomographic studies in parkinsonian patients will therefore not be altered by 3OMD present in the blood in those patients taking L-dopa preparations. These results do not support the hypothesis that transport of L-dopa into the brain is inhibited by 3OMD to cause the declining response seen in patients with advanced Parkinson's disease.

Amino Acid Transport Systems↗
PubMed1991

New surprises in very old places: Civil War nurse leaders and longevity.

While the average woman in the U.S. Civil War times lived to the age of about 40, a group of 17 extraordinary nurses--including Louisa Mae Alcott, Dorothea Dix, and Clara Barton--survived to much older ages. A variety of possible reasons, from social and marital status to altruism and religion, is explored. More than any tangible factor, however, the presence of a "pioneering spirit" seems to be at the root of their longevity.

Attitude of Health Personnel↗
PubMed1990

Primary care obstetrics in rural western New York. A multi-center case review.

Obstetric care in rural communities is in crisis due to the shortage of practitioners and the pressures of regulatory agencies on small obstetric units. We reviewed the records of 297 pregnant women presenting to the offices of 12 family physicians in rural areas of Western New York State. Local deliveries were done in rural hospitals that reported fewer than 500 deliveries per year. Family physicians obtained consultation in 36% of the pregnancies. Of these, care responsibility was transferred to an obstetrician 50% of the time (18% of all pregnancies). Two percent of the cases were transferred to a regional referral center. There was one perinatal death and one intrauterine fetal death in this series. Of the 222 deliveries by family physicians, oxytocin was used in 23%, narcotic analgesia was used in 15.3%, and outlet assist in 8.1%. Labors were somewhat longer than standard labor curves, and the overall cesarean section rate was 13.5%. We conclude that obstetric care by rural family physicians utilizing small rural Western New York hospitals is consistent with standards of care elsewhere when practiced in the context of an organized referral network.

Family Practice↗
PubMed1989

The effect of dietary protein on the efficacy of L-dopa: a double-blind study.

We randomly placed 10 parkinsonian patients on high- and low-protein diets that tasted and looked alike, each for 1 week. All patients were taking L-dopa and carbidopa with or without other antiparkinson medications; medications remained unchanged. A "blind" physician recorded the modified Columbia scores, objective measurements of rigidity, movement velocity, and pegboard tests three times a day for 5 days during each week. The patients recorded fluctuations hour to hour. We measured serial blood L-dopa levels on day 4 of each week. Performance was significantly better while the patients were on low-protein diets. These results did not correlate with blood L-dopa levels, which had higher peaks in three patients while they were on high-protein diets despite inferior performance and increased number of "off" hours. Thus, high dietary protein probably affects the efficacy of L-dopa at a central level.

Antiparkinson Agents↗
PubMed1988

Response to brief levodopa infusions in parkinsonian patients with and without motor fluctuations.

The fluctuating response to levodopa may result from progressive loss of striatal dopamine terminals and consequently increasingly impaired dopamine storage capacity. This hypothesis predicts that the acute response to levodopa would shorten with increasing disease severity. To test this, we compared the duration of improvement in tapping and walking speeds following discontinuation of 2-hour levodopa infusions in nine previously untreated (UT), seven stable (ST), and 17 fluctuating (FL) subjects. Mean Hoehn and Yahr disability in the morning prior to levodopa infusion was 2.8, 2.2, and 4.4 for UT, ST, and FL subjects. Six of nine UT, six of seven ST, and all FL subjects exhibited improvement with the infusions, which produced similar peak plasma levodopa levels in all groups. The duration of the response was similar in the ST and FL groups. The response in the UT group was heterogeneous; in three, the response was of similar length as compared with the ST and FL groups, but was longer in the other three UT subjects. The correlation between disease severity and response duration was poor. The ST and FL groups, while differing in disease severity, exhibited a similar duration of response to levodopa infusion. This does not support a reduced dopamine "storage capacity" as the sole explanation for the length of the short-duration response. Furthermore, motor fluctuations appear to be present from early in treatment, but only become noticeable when "off" disability becomes marked.

Aged↗
PubMed1985

Bacterial interactions in bovine respiratory and reproductive infections.

The ability of the aerobic bacterial flora from the normal bovine respiratory and reproductive tracts to enhance or inhibit the growth of Pasteurella haemolytica, P. multocida, and Haemophilus somnus was tested in vitro. Six strains of each of these pathogens were cross streaked with each isolate of bovine normal flora. Flora which enhanced the growth of these pathogenic bacteria outnumbered inhibitors four to one. An intermediate number of isolates produced no effect on pathogen growth. Most enhancers were gram positive (Micrococcus, Staphylococcus, Corynebacterium, or Rhodococcus isolates), although several isolates of Moraxella and Actinobacter were also good enhancers. For H. somnus, there were proportionally more organisms which produced marked enhancement among the preputial flora than among the nasal flora, which may account for the greater number of genital carriers than nasal carriers. Bacillus isolates were the most significant inhibitors among the nasal flora, whereas no genus or species from the reproductive tract was noted to produce appreciable inhibition. It is proposed that changes in ratios of inhibitors to enhancers may determine, in part, whether a carrier state or disease occurs. Also, suggestions are made for in vitro use of this phenomenon for diagnostic tests.

Animals↗
PubMed1983

Analysis of surgical versus medical therapy in active complicated native valve infective endocarditis.

From 1972 to 1980, 23 patients (Group A) with native valve infective endocarditis underwent surgical intervention, often for multiple indications, during the active stage of the infective process because of progressive class III and IV (New York Heart Association) heart failure (12 patients), persistent severe hypotension (3 patients), uncontrolled infection for over 21 days (11 patients), aortic root abscess (2 patients), and pericarditis (1 patient). Eighty-five patients (Group B) with active native valve endocarditis, matched for severity of illness, were treated medically. Two patients (9%) in Group A and 43 patients (51%) in Group B died during the hospital admission (p less than 0.001). Any difference in long-term cumulative survival rate between the 2 groups was largely due to the beneficial impact of surgical management on the hospital mortality. Of 23 patients in Group A, 11 (48%) had an entirely uncomplicated postoperative course. Long-term mortality rates in those with aortic valve endocarditis treated medically (79%) were significantly higher than in those with mitral valve involvement (47%) (p less than 0.05). Patients with aortic valve involvement treated surgically had a better hospital (p less than 0.005) and long-term (p less than 0.0005) survival rate than those treated medically. Two groups at risk for postoperative complications were identified; 3 of 11 patients (27%) with uncontrolled infection had an early postoperative recurrence, and 4 of 7 patients (57%) with an aortic root abscess had postoperative prosthetic paravalvular regurgitation. Surgery therefore effects a substantial reduction in hospital mortality in patients with complicated active infective endocarditis (9% versus 51%), but patients with preoperative prolonged periods of uncontrolled infection or with aortic root abscess are liable to postoperative complications.

Adolescent↗
PubMed1983

Circadian rhythm of hourly ventricular arrhythmia frequency in man.

Three twenty-four hour electrocardiographic recordings from 164 untreated patients were analyzed. A clear, statistically significant, diurnal pattern in hourly ventricular arrhythmia frequency was found. It was consistent across days and between seven diagnostic groups. A high frequency Noon to 4:00 PM peak contrasted with a low frequency 1:00 AM to 5:00 AM trough with zero hourly frequencies not uncommonly present. These findings appear applicable to large ambulatory populations and may well influence the design of future investigations of modalities which alter ventricular arrhythmia frequency.

Aged↗
PubMed1982

Clinical implications of anterior S-T segment depression in patients with acute inferior myocardial infarction.

To assess various factors associated with anterior S-T segment depression during acute inferior myocardial infarction, 47 consecutive patients with electrocardiographic evidence of a first transmural inferior infarction were studied prospectively with radionuclide ventriculography an average of 7.3 hours (range 2.9 to 15.3) after the onset of symptoms. Thirty-nine patients (Group I) had anterior S-T depression in the initial electrocardiogram and 8 (Group II) did not have such "reciprocal" changes. There was no difference between the two groups in left ventricular end-diastolic or end-diastolic volume index or left ventricular ejection fraction. Stroke volume index was greater in Group I than in Group II. There were no group differences in left ventricular total or regional wall motion scores. A weak correlation existed between the quantities (mV) or inferior S-T segment elevation and reciprocal S-T depression. No relation between anterior S-T segment depression and the left ventricular end-diastolic volume index could be demonstrated; the extent of left ventricular apical and right ventricular wall motion abnormalities, both frequently associated with inferior infarction, did not correlate with the quantity of anterior S-T depression. These data show that anterior S-T segment depression occurs commonly during the early evolution of transmural inferior infarction, is not generally a marker of functionally significant anterior ischemia and cannot be used to predict left ventricular function in individual patients. Anterior S-T segment depression may be determined by reciprocal mechanisms.

Cardiac Catheterization↗
PubMed1981

Double-blind, randomized, placebo-controlled comparison of propranolol and verapamil in the treatment of patients with stable angina pectoris.

This study was performed to compare the relative efficacies of propranolol and verapamil in patients with stable angina pectoris. In 18 patients (16 men, two women, mean age 58 years) with coronary artery disease and angina of effort, the results of low (40 mg every 6 hours) and high-dose (80 mg every 6 hours) propranolol therapy were compared to those of low (80 mg every 6 hours) and high-dose (120 mg every 6 hours) verapamil therapy in a double-blind, randomized, placebo-controlled evaluation which lasted eight weeks: two weeks of placebo therapy, two weeks of propranolol or verapamil (one week low-dose, one week high-dose) therapy, three days of down-titration followed by one week of placebo therapy, two weeks of propranolol or verapamil therapy (whichever was not given earlier in the trial) (one week low-dose, one week hgh-dose) and three days of down-titration. During each period the following were quantitated: (1) chest pains/week; (2) nitroglycerin used/week; (3) transient ischemic S-T segment deviations and highest grade of ventricular ectopic activity on two-channel Holter monitor; (4) S-T segment deviations during supine bicycle exercise; (5) left ventricular volumes and ejection fraction at rest and during exercise (assessed by equilibrium gated blood pool scintigraphy); and (6) pulmonary function studies. Propranolol and high-dose verapamil therapy significantly reduced the frequency of angina, and high-dose verapamil therapy diminished both the need for nitroglycerin and the frequency of transient ischemic S-T segment deviations on Holter monitor. Neither agent exerted a clinically-important deleterious influence on left ventricular volumes or the ejection fraction. Forced vital capacity and forced expiratory volume were worsened by propranolol but not by verapamil. Thus, in the patient with angina of effort, verapamil is a satisfactory therapeutic alternative to propranolol.

Adult↗
PubMed1981

The prognostic value of submaximal exercise testing with radionuclide ventriculography before hospital discharge in patients with recent myocardial infarction.

To test the hypothesis that patients at risk of future cardiac events can be identified by sub-maximal exercise testing with radionuclide ventriculography (RVG), 61 patients were studied a mean of 19 +/- 1.0 days (+/- SEM) after acute myocardial infarction (MI). RVGs were used to measure left ventricular ejection fraction (LVEF), wall motion score (WMS), end-diastolic volume (EDV) and end-systolic volume (ESV), and the ratio of systolic blood pressure to ESV (P/V index) at rest and during submaximal exercise. Frank lead ECGs were analyzed for ST-segment change and arrhythmias. These patients were followed for a mean of 9.6 months (60 for 6 months or more and one for 3 months) to determine the incidence of cardiac death, recurrent MI, unstable or medically refractory angina, persistent congestive heart failure (CHF) or limiting angina; these problems were considered to be important cardiac events. At the 6-month follow-up, 37 patients had important complications: four patients died, five had MI, seven had unstable or medically refractory angina, 11 had persistent CHF and 10 had severe limiting angina. The sensitivity and specificity of RVG in predicting the important postinfarct complications listed above were 95% and 96% for failure to increase LVEF by at least 5 units, 95% and 96% for an increase in ESV of more than 5%, 97% and 88% for failure of the P/V index to increase by more than 35%, and 81% and 88%, respectively, for a decrease in WMS. The sensitivity and specificity of the ECG in predicting important complications were 54% and 58%, respectively. The rest and submaximal exercise RVG variables, the ECG, a history of MI, the location of the infarction, Killip class III, age, sex, and maximal work load performed were analyzed statistically to determine the best predictors of prognosis. The change with exercise in LVEF, ESV and the P/V index were most significant variables in predicting prognosis during the 6-month follow-up period. When patients with subsequent cardiac events were separated into those with death, recurrent MI and unstable or medically refractory angina as major cardiac events, and patients with persistent CHF and limiting angina as less important ("minor") cardiac events, only the peak submaximal exercise LVEF and history of MI were significant in distinguishing these groups. In patients without important cardiac events during the 3- and 6-month follow-up, 70% and 88%, respectively, no abnormality in the responses of LVEF, ESV, or P/V index to submaximal exercise. These results suggest that submaximal exercise testing with RVG is a highly sensitive means of classifying patients at the time of hospital discharge after MI according to the likelihood of having cardiac events during the ensuing 6 months.

Adult↗
PubMed1976

Attenuated, streptomycin-dependent Salmonella typhi oral vaccine: potential deleterious effects of lyophilization.

Four studies were done with streptomycin-dependent Salmonella typhi as an oral, attenuated vaccine. Studies 1 and 3 employed freshly harvested vaccine, whereas studies 2 and 4 involved lyophilized vaccine. Five to eight doses (3 x 10(10)-10(11) organisms/dose) were given; oral streptomycin (1.0 g) was administered concomitantly in studies 2 and 3, with only two of the doses of vaccine in study 1, and was not given in study 4. No adverse reactions were encountered in 179 vaccinated men, and 94% of the men excreted the vaccine. In challenge studies (which included the control groups) with 10(5) virulent S. typhi organisms (Quailes strain), the fresh vaccine was highly protective (66%-78% efficacy), while lyophilized vaccine gave no clinical protection. Fresh vaccine also interfered significantly with intestinal proliferation of virulent S. typhi; only 17% of the vaccinees excreted organisms as compared with 75% of the controls. Studies of protection in mice showed no difference between immunogen content of the fresh and the lyophilized vaccines. Field trials with streptomycin-dependent, oral typhoid vaccine must await development of a lyophilized product that will retain the protective properties of the vaccine.

Administration, Oral↗
PubMed1975

In vivo recovery of muscle contraction after alpha-bungarotoxin binding.

Acetylcholine receptors were inactivated in vivo at the mouse neuromuscular junction using alpha-bungarotoxin (alpha-BTX). It was found that neurally produced muscle contraction recovered within 4-8 days (halftime similar to 3 days). Actinomycin D interfered with this recovery, but did not affect normal nerve-stimulated muscle contraction. If the response was initially eliminated by [125-I]alpha-BTX and the end plates examined by EM autoradiography, no evidence of mass internalization of bound radioactivity during recovery was seen. The fine structure of the end plates and muscle was unaltered during the post-alpha-BTX recovery period.

Acetylcholine↗