Audrey S. Penn

Nontraumatic Rhabdomyolysis and Acute Renal Failure

Abstract Rhabdomyolysis with myoglobinuria from nontraumatic causes was the sole identifiable explanation for acute renal failure in 15 patients during a three-year period. Myoglobinuria resulted f...

The thymus in myasthenia gravis. Evidence for altered cell populations

Abstract Comparisons of several types of immunologic reactivity were made in thymic cells from six patients with myasthenia gravis and thymic hyperplasia, four patients with myasthenia gravis and thymoma and six age-matched control cardiac-surgery patients. In mixed leukocyte reactions, thymic cells from the subjects with hyperplasia were capable of stimulating autologous peripheral blood lymphocytes. Such reactivity was not seen in thymocyte-blood lymphocyte mixtures from the other two groups. There was an increased number of B cells in the thymic-cell populations from the myasthenic patients as compared to that in the control group, carrying predominantly IgM receptors. The thymic cells from myasthenic patients also responded more vigorously to pokeweed mitogen. These findings suggest altered populations of lymphoid cells in the thymus of myasthenic patients that react with autologous lymphocytes from other cell compartments. The pathogenic implications of these findings remain to be determined. (N Engl...

A Rational Approach to Total Thymectomy in the Treatment of Myasthenia Gravis

Thymectomy is important in the treatment of myasthenia gravis. Total removal of the gland is considered indicated. Although median sternotomy has been the accepted surgical procedure, the transcervical approach has been advocated as a safer method of achieving total thymectomy. A surgical-anatomical study of the thymus was made in 22 patients. A high incidence of surgically important variations in thymic anatomy was found in the neck and in the mediastinum. We believe wide exposure by way of median sternotomy with direct vision is required to remove all of the extracapsular mediastinal thymus in many patients, and good cervical exposure is required to remove the anomalous tissue in the neck. If a total thymectomy is to be achieved, we recommend a median sternotomy and a cervical incision, using the meticulous dissection described.

Complement‐fixing antiperipheral nerve myelin antibodies in patients with inflammatory polyneuritis and with polyneuropathy and paraproteinemia

Serum from patients with peripheral neuropathies was tested for antiperipheral nerve myelin antibodies by complement fixation. Antibody activity was detected in 5 of 20 patients with acute or chronic remitting polyneuritis and in 4 of 20 patients with polyneuropathy and paraproteinemia but not in patients with other types of neuropathy, neurologic disease, or immunologic disease. In three patients with IgM paraproteinemia, the complement-fixing activity resided in the IgM fraction; in one patient with chronic inflammatory polyneuritis, antibody activity resided in the IgG fraction. In the inflammatory polyneuropathies, antibody titers did not always correlate with disease activity. Sera from patients with remitting polyneuropathies reacted with either human or rabbit peripheral nerve myelin, but sera from patients with paraproteinemia reacted only with human myelin.

Presumably Azorean disease in a presumably non‐Portuguese family

Autosomal dominant motor system degeneration (ADMSD) is a hereditary ataxia that has been reported previously only in Portuguese families from the Azores Islands. Cerebellar ataxia, pyramidal and extrapyramidal signs, amyotrophy, dystonia, abnormal eye movements, and prominent eyes are variably present. Four members of a family had cerebellar ataxia, dystonic posturing, a variety of abnormal eye movements, and prominent eyes resulting from lid retraction. Eight other family members had a similar disease. The combination of cerebellar ataxia, dystonia, abnormal eye movements, and prominent eyes has been reported only in ADMSD. The family reported here may be the first example of ADMSD in a non-Portuguese family.

Severe dystonia and myoglobinuria

Myoglobinuria may follow extreme muscular exertion or disorders that cause muscle necrosis. Dystonia has not been implicated previously. We studied an 8-year-old boy of non-Jewish, Mexican-American descent with autosomal-dominant dystonia musculorum deformans who developed rapidly progressive and severe generalized dystonia, hyperpyrexia, myoglobinuria, and renal failure. Curarization was required. Transient improvement was achieved with tetrabenazine and baclofen, but bilateral thalamotomy was then performed. Patients with severe dystonia should be observed for evidence of myoglobinuria.

ANTIBODIES TO ACETYLCHOLINE RECEPTORS IN RABBITS: IMMUNOCHEMICAL AND ELECTROPHYSIOLOGICAL STUDIES*

Acetylcholine receptors (AChR), purified from electric eel and Torpedo by affinity chromatography using a synthetic quaternary ammonium ligand, bound 10 nmole alpha-bungarotoxin (alpha-BuTx) per mg of protein and demonstrated a common subunit. Rabbits, immunized with either eel or Torpedo/AChR, developed flaccid paralysis barely altered by anticholinesterases and died 48 hours after the first sign of paralysis. In paralyzed animals, repetitive stimulation at low rates induced a 50% to 90% decrement of evoked potentials, temporarily reversed by edrophonium. Extracellular and introcellular MEPP amplitudes were 40% to 50% of controls. Serum and isolated IgG formed single immunoprecipitin lines against the antigens. AChR-antibody complexes did not bind alpha-BuTx, whereas alpha-BuTx-AChR complexes bound antibody if the antibody was specific for that AChR. Torpedo and eel AChR showed partial idenity with both antisera. Rat diaphragms and eel electroplax incubated with antisera to Torpedo and eel AChR showed a 50%-60% reduction in carbamylcholine depolarization. These studies demonstrate differences between eel and Torpedo AChR induce a block in neuromuscular transmission in rabbits with features of myasthenia gravis.

Auto‐Anti‐Idiotype: A Basis for Autoimmunity and a Strategy for Anti‐Receptor Antibodies

As frequently seems to be the ease, a series of serendipitous findings has shaped the overall objectives of research being carried oul in our laboratory. The first was the discovery of a highly potent agonist of the nicotinic acetylcholine receptor (AChR). tran.s-i.y -bis[«-trimethy!ammonio)-methyl]azobenzene (BisQ) (Bartels ct al. 1971. Wassermann et al. 1979) at a time when we were interested In photoregulating AChR activity (Erlanger 1976, Erlanger et al. 1982, 1983). Then, some casual hypothesizing and simple immunochemical experiments followed and we were thrust into the complex world of idiotypy. anti-idiotypy and autoimmunity, from which we will probably never escape alive. The objectives of our research can be characterized as follows: 1. To study the biological and biochemical properties of anti-idiotypic antibodies in relation to the etiology of such autoimmune diseases as myasthenia gravis (MG) and Graves disease. 2. To Investigate the full potential of an auto-anti-idiotypic strategy for the preparation of anti-receptor antibodies. With respect to the first objective, we will present data in support of the view that products of a functioning anti-idiotype network can cause an autoimmune disease, specifically the experimental form of myasthenia gravis (MG). It will be

Muscular dystrophy in young girls.

SEVERAL RESPECTED authorities have stated that the Duchenne form of muscular dystrophy may occur in girls,l-6 and some have postulated an autosomal recessive form of the same disease.3-7 Yet there is strong evidence that Duchenne dystrophy is inherited in an Xlinked recessive pattern.298-18 Others have therefore invoked the Lyon hypothesis to explain the cases in girls.lg-21 It is also possible, of course, that the girls have a different disease which merely resembles Duchenne dystrophy. In our own experience, cases clinically resembling muscular dystrophy in young girls differ in essentials from the disease in boys. Because of this discrepancy, we analyzed our cases and scrutinized all previously reported cases diagnosed as Duchenne dystrophy in girls. The disease in the latter group was also very atypical and laboratory confirmation was almost always lacking. Theoretically, it is possible that Duchenne dystrophy does occur in girls, but complete documentation of a single case is not yet available and awaits elucidation of the biochemical defect.

Potentially fata1 cardiac dysrhythmia and hyperkalemic periodic paralysis

An 11-year-old boy was evaluated for mild periodic muscular weakness exacerbated on separate occasions by disopyramide phosphate and procainamide. He and his mother both had bidirectional ventricular tachydys-rhythmia (BVT), short stature, microcephaly, and clinodactyly. The mother, but not the child, had lingual myotonia. The two antiarrhythmic drugs worsened the muscular weakness without benefiting the cardiac dysrhythmia. Potassium loading produced skeletal muscle weakness and transient conversion of the BVT to normal sinus rhythm. Hypokalemia aggravated the BVT without causing weakness. Acetazolamide had no effect. The patient suffered a nonfatal cardiac arrest after several days of increased carbohydrate intake. Imipramine controlled the dysrhythmia without inducing weakness. Periodic paralysis should be considered as the diagnosis in children with BVT, a potentially fatal condition.