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Biomedical subjects

W H Muller

Publications and source records attributed to W H Muller.

At least 19 recordsLinked to original sources
PubMed1998

Reduced thiopurine methyltransferase activity and development of side effects of azathioprine treatment in patients with rheumatoid arthritis.

OBJECTIVE: To investigate thiopurine enzyme activities for their possible value in predicting the development of azathioprine (AZA)-related toxicity in patients with rheumatoid arthritis (RA). METHODS: Patients with longstanding RA (n = 33) were enrolled in a study of treatment with AZA. Before the initiation of AZA treatment and at months 1 and 6 of treatment, we measured activities of the purine key enzymes hypoxanthine guanine phosphoribosyltransferase, 5'-nucleotidase, purine nucleoside phosphorylase, and thiopurine methyltransferase (TPMT). Controls included patients with early RA (n = 24) and healthy volunteers (n = 42). RESULTS: Fourteen of the 33 patients rapidly developed severe side effects, most frequently gastrointestinal (GI) intolerance. Compared with the other groups, the group with adverse effects had significantly lower TPMT activities (P = 0.004). Seven of 8 patients with reduced ("intermediate") baseline TPMT levels developed toxicity, resulting in a significant relationship (P = 0.005) between toxicity and "intermediate" TPMT activity. Compared with "high" activity, baseline intermediate TPMT activity gave a relative risk of 3.1 (95% confidence interval 1.6-6.2) for the development of severe toxicity with AZA treatment. CONCLUSION: In RA patients, inherited intermediate TPMT activity seems predictive for the development of severe side effects of AZA. Clinicians should consider measuring TPMT prior to treatment initiation to improve the safety of AZA use. We hypothesize that GI intolerance may also be related to a thiopurine metabolic imbalance.

Adult↗
PubMed1991

Methotrexate versus azathioprine in the treatment of rheumatoid arthritis. A forty-eight-week randomized, double-blind trial.

We conducted a double-blind, randomized trial comparing azathioprine (AZA) and methotrexate (MTX) in the treatment of patients with rheumatoid arthritis in whom parenteral gold and/or D-penicillamine treatment had been unsuccessful. Patients were randomly assigned to receive either AZA (100 mg daily) or oral MTX (7.5 mg weekly). After 8 weeks, the dosage was increased depending on the clinical improvement. Sixty-four patients were followed up for 48 weeks (33 AZA, 31 MTX). Comparison of values at week 24 with baseline values revealed significant improvement in 12 of 13 disease variables in the MTX group and in 6 of 13 in the AZA group. Comparison between the 2 treatment groups at 24 weeks, by area-under-the-curve analysis, showed significantly more improvement in the MTX group in terms of the swollen joint count, pain score, erythrocyte sedimentation rate, C-reactive protein level, hemoglobin level, thrombocyte level, and disease activity score. A significant overall clinical improvement (disease activity score) was found in 7 of 20 patients treated with AZA and 18 of 30 patients treated with MTX after 24 weeks of therapy, and in 6 of 12 AZA-treated patients and 19 of 25 MTX-treated patients after 48 weeks. The number of withdrawals due to side effects was significantly higher in the AZA group. After 48 weeks, only 12 patients from the AZA group (36%), but 25 from the MTX group (81%), were still using the initial drug. These results demonstrate MTX to be superior to AZA in the treatment of rheumatoid arthritis, with a more rapid clinical improvement which is sustained after 1 year, accompanied by a lower rate of serious adverse reactions.

Adrenal Cortex Hormones↗
PubMed1989

Pulmonary artery banding revisited.

Pulmonary artery (PA) banding to reduce pulmonary blood flow was described by Muller and Dammann in 1952. This review describes the outcome of 170 children who had PA banding at the University of Virginia Medical Center between 1955 and 1988. One hundred and one of the patients were banded between 1958 and 1970; fewer bands were placed in later years because early total correction was feasible for certain conditions. When analyzed by preoperative diagnoses, the data reveal that children with a single ventricle undergoing banding had a significantly lower 30-day mortality rate of 12% compared to other preoperative diagnoses, including atrioventricular canal, truncus arteriosus, and ventricular septal defect (VSD) at 30% (p less than 0.05). The late overall mortality for all patients was approximately 10%, an attrition rate of 1% per year. PA banding still has a role in management of patients with congenital heart disease, particularly for infants with a single ventricle. Actuarial survival at 10 years for patients with this condition is 92%. Interestingly, this indication for pulmonary banding is the same one cited in the original report.

Aortic Coarctation↗
PubMed1985

Can success in the surgical residency be predicted from preresidency evaluation?

Sixty-two residents entered the general surgical residency over a 10-year period, and 42 completed it. When the 20 who were dismissed from the program were compared by discriminant analysis to those who completed it successfully, it was found that Alpha Omega Alpha (AOA) membership, high class rank, clinical honors, and publications predicted success with 89% accuracy. Ten of the 42 who completed the program were rated as outstanding, 22 were average and 10 below average. No subjective or objective preresidency selection data correlated with later chief resident performance.

Educational Measurement↗
PubMed1984

Sexual problems in rheumatoid arthritis and ankylosing spondylitis.

In this study, scores on the sexual motivation scale (which measures the tendency to engage in sexual interaction versus the tendency to be averse to sexual interaction) were determined, by interview, in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients and compared with the scores of healthy matched controls. AS patients did not score differently from the healthy population, but scores of men and women with RA were more in the direction of sexual aversion than those of healthy men and women. In female RA patients, some relationship was found between disease variables such as joint index and erythrocyte sedimentation rate and the score on the sexual motivation scale. In the second part of the interview, preference for certain coital positions was investigated, and the demand for help with sexual problems was explored. The percentage of RA patients expressing a need for advice was considerably greater than the percentage of AS patients.

Adolescent↗
PubMed1981

Critical analysis of the preoperative and operative predictors of aortocoronary bypass patency.

A prospective analysis of the angiographic and operative anatomic and reconstructive variables that influenced graft patency was undertaken at the University of Virginia Medical Center in 50 consecutive patients. Postoperative restudy showed that 18 of the 168 grafts performed were occluded due to venous disease, inadequate run-off, or sequential design error. Angiographic artery size was 27% larger than operative estimations; graft patency significantly increased with increasing distal artery diameter, with decreasing venous conduit diameter, and with good graftability rating of the vessels preoperatively. Ejection fraction, the degree of arterial stenosis, and the source of the saphenous vein conduit (the thigh or the lower leg) had no influence on graft patency. Simple grafts had a 96% patency, while sequential grafts had an 80% patency. When design error for sequential grafts was eliminated, the sequential patency rate rose to 88%. For revascularization of small circumflex vessels, consideration should be given to variation in the sequential grafting technique to improve patency in these vessels.

Coronary Angiography↗
PubMed1981

Intercostal muscle biopsy studies in myasthenia gravis: clinical correlations and the direct effects of drugs and myasthenic serum.

We have found a wide range of mean MEPP amplitude in intercostal muscle biopsies from 43 patients with MG, including several values in the normal range. There was no correlation between MEPP amplitude and the severity of clinical disease as assessed by manual muscle testing or by single-fiber EMG measurements of jitter in arm muscles. Through most of these patients were in a state of clinical remission or marked improvement after treatment with prednisone, we could not attribute the difference between our results and those of others to this factor alone. The application of morphine, meperidine and aminoglycoside antibiotics to intercostal muscle in vitro confirms effects previously demonstrated in rat muscle: (1) At equal therapeutic concentrations, meperidine has greater neuromuscular blocking effects than does morphine, but neither has significant effects at concentrations achieved in the serum clinically. (2) Tobramycin, netilmicin and neomycin have varying severity and sites of action, but their effects are the same in human myasthenic muscle as in normal rat muscle. Bath application of serum from myasthenic patients produces an acute, reversible worsening of neuromuscular blockade in myasthenic muscle. Electrophysiologic measurements in intercostal biopsies from patients with MG can provide information about the basic abnormality of neuromuscular transmission in this disease and can confirm the relevance of studies made in animal muscle.

Action Potentials↗
PubMed1980

Employability--a new indication for aneurysmectomy and coronary revascularization.

Increasing governmental concern with containment of medical costs prompted us to evaluate the efficacy and cost effectiveness of ventricular aneurysmectomy and coronary revascularization. Sixty-six patients underwent ventricular aneurysmectomy between August 1973 and June 1978. Their classification according to the New York Heart Association criteria, their employment status (fully employed, working part time or totally disabled) and their salaries and disability payments for the 11-month periods before and after surgery were compared. There were five hospital deaths (7.6%) with a 40-month actuarial survival of 74%. Ninety-five percent percent of the survivors were class I or class II 20 months (average) postoperatively, full employment increased form 33% preoperatively to 63% postoperatively and total disability decreased from 60% preoperatively to 29% postoperatively. The efficacy of surgery in this group of patients in terms of financial implact on the community was analysed: the cost of surgery averaged $10,537.00 per patient. Computing the income actually earned by the entire group of patients, the disability payments to the individual patients and the lost tax revenues through disability shows that the cost of surgery for the whole group could be paid by 1.68 years of improved postoperative productivity.

Adult↗
PubMed1978

Observations on the pathogenesis and management of pulmonary hypertension.

Experimental subclavian-pulmonary and aorta-pulmonary anastomoses were performed in attempts to produce progressively increasing pulmonary vascular changes and to observe their sequential development. At six weeks after anastomosis there was medial hypertrophy, at eight weeks total involvement of the artery, and at eleven weeks severe pulmonary vascular disease, total decrease in the number of capillaries, and complete obstruction of the lumen. These pathologic changes are compared with the normal course of events in the fetal and postnatal lung. A series of patients with patent ductus arteriosus, single ventricle, and a large ventricular septal defect were studied and categorized into three phases according to the severity of their clinical symptoms. A method for producing pulmonary artery stenosis in the laboratory as applied to a three month old infant is discussed.

Animals↗
PubMed1977

Factors influencing survival of patients with permanent cardiac pacemakers.

With the advent of permanent cardiac pacing, technology has produced power sources that will last two, four, and even 20 years. The cost of these devices is proportional to their complexity and expected life. Therefore, the selection of an appropriate pulse generator should be based on the patient's prognosis. An actuarial analysis of 319 consecutive patients receiving permanent cardiac pacemakers was performed in order to determine whether prepacing factors influenced prognosis. The survival probability at 5 years was not influenced by sex, race, type of conduction defect, or antecedent disease. Survival rate decreased only slightly for each decade of life, but even in the ninth decade there was an acceptable prognosis.

Age Factors↗
PubMed1976

Long-term prednisone followed by thymectomy in myasthenia gravis.

The present series of thirty patients has led us to certain conclusions concerning the management and treatment of patients with myasthenia gravis. The use of cholinesterase inhibitors alone is reserved for those patients with purely ocular myasthenia whose deficits can be satisfactorily corrected with those agents. Some of those with ocular involvement may be disabled; and in light of our excellent results with that small group, as well as similar findings presented by Fischer et al., patients with disabling or refractory ocular myasthenia should be considered for treatment with prednisone. All other patients with myasthenia are given a course of oral corticosteroids (prednisone) initially at high doses, with subsequent tapering to maintenance, alternate-day low-dose therapy. Cholinesterase inhibitors are used as needed while the patient is receiving corticosteroids. We now anticipate that patients will exhibit sustained improvement within the first two weeks, reaching maximal improvement at about three months. Exacerbations of myasthenic weakness may occur in the early phases of treatment. Such exacerbations have been commonly mild and occur with a mean onset at 5 days, and have a mean duration of 6 days. Most patients have been able to tolerate an alternate-day schedule of prednisone therapy when maintenance levels were achieved. The effective maintenance dose has been determined as the smallest dose of prednisone which allows the patient to maintain maximal improvement. Following the establishment of maximal improvement, patients have been considered for thymectomy. In our experience, the sternum-splitting procedure has been tolerated extremely well by patients exhibiting marked imporvement or remission while on corticosteroids. In those patients where thymectomy is contraindicated, irradiation of the thymus might be considered. Patients are continued on maintenance steroid therapy following surgery for a period of time that has been arbitrary. Currently, we consider an attempt to discontinue steroids at approximately one year reasonable. Should the patient relapse after discontinuation of the medication, oral corticosteroid treatment is reinitiated. Consideration is given to the possibility of recurrent thymus in patients who repeatedly fail to maintain a remission when steroids have been stopped. Our experience has not permitted us to draw firm conclusions concerning how long a time high-dose daily steroid treatment should be continued in patients who show no favorable response to that therapy. Other modes of treatment, such as courses of parenteral ACTH, methyl prednisolone, dexamethazone, or antimetabolites might be considered if there is no response after 12 weeks of high-dose, daily corticosteroid therapy.

Adolescent↗