William H. Muller

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.

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.

An experimental study of resection and replacement of the superior vena cava

Abstract A review of the literature on the treatment of obstruction of the superior vena cava and its replacement is presented. Experiments were performed on fourteen dogs using nylon and teflon prostheses for replacement. Edwards-Tapp nylon prostheses were implanted in seven dogs, two of which had undergone partial occlusion of the superior vena cava. Teflon tubes were used for replacement of the superior vena cava in the remaining seven animals, one of which had undergone partial ligation of the superior vena cava and transaction of the azygos vein. The teflon prostheses showed excellent results in seven dogs followed up to six months. Superior vena caval prostheses of nylon in the other seven dogs were less successful as shown by necropsy with narrowing in all the prostheses. Only one animal in this group, however, had complete occlusion by thrombus, and in the remaining six there was no clinical evidence of obstruction, and venous pressures remained normal postoperatively.

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.

Experimental pulmonary arterial hypertension

Abstract A brief review of previously described methods of producing experimental pulmonary hypertension has been presented. Three technics that we have used in attempting to induce pulmonary arterial disease are described. These technics were: (1) creation of interventricular septal defects in fetal puppies, (2) the administration of serotonin to newborn rats, and (3) systemic-lobar-pulmonary arterial anastomoses in dogs. The systemic-lobar-pulmonary arterial anastomoses proved to be the most satisfactory technic and produced pulmonary arterial lesions similar to those seen in man in the majority of survivors in this group of animals. The reversibility of these changes was determined by histologic study of the lung following anastomotic restoration of the pulmonary artery to the involved lobe. Those animals showing both medial hypertrophy and intimal hyperplasia demonstrated a significant increase in the cross-sectional area of the pulmonary arteries following the reversal operation. Medial hypertrophy alone or with minimal intimal sclerosis appeared to regress at a slower rate but in no instance did a progression of the observed changes occur.

Acute myasthenia gravis following surgery for acute dissecting aortic aneurysm under nitrous oxide, pentothal-curare anesthesia

Abstract Curare anesthesia is contraindicated in patients known to have myasthenia gravis. However, occasionally a surgical emergency arises and operation is performed on a patient not known to have the disease or with so-called latent myasthenia gravis. This was true of a case seen at the University of Virginia Hospital. Using nitrous oxide, sodium pentothal and curare anesthesia with hypothermia, surgical repair of an acute dissecting aortic aneurysm was performed on a sixty-two year old white man in whom a myasthenic crisis developed as a result of surgery and anesthesia. The patient died on the fourteenth postoperative day in spite of cholinergic medications and efforts to maintain adequate respiratory function. Postmortem examination revealed satisfactory repair of the acute dissecting aneurysm with death due to tracheobronchitis and pneumonitis. The case history is presented and the general problem is discussed.

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.

The evolution and current concepts of the surgical treatment of constrictive pericarditis

Summary The history of constrictive pericarditis has been summarized with emphasis upon the surgical approach to its treatment. The important aspects of the etiology, pathologic physiology and diagnosis of this disease have been discussed. The surgical treatment of constrictive pericarditis has been reviewed with particular stress upon the technics of pericardiectomy. Certain controversial points have been emphasized. The most significant of these concerns the approach to be used and the extent of pericardiectomy which will provide the best results with the least risk. Although no answers are provided to these or to other disputed questions, certain preferences are implied. Finally, the evaluation of surgical therapy is discussed and the composite results of many reported series are presented along with the more recent experience at the University of Virginia Medical Center.