PubMed Health⌕ Search

Biomedical subjects

J R Mendell

Publications and source records attributed to J R Mendell.

At least 163 records · Page 9Linked to original sources
PubMed1985

Clinical investigation in Duchenne dystrophy: V. Use of creatine kinase and pyruvate kinase in carrier detection.

We have determined the value of creatine and pyruvate kinase (CK and PK) in carrier detection by evaluating 811 females in 73 families participating in the Collaborative Investigation of Duchenne Dystrophy. Thirty-nine obligate carriers, 244 normal controls (paternal females), as well as 76 possible carriers and 351 carrier suspects had three CK and PK specimens analyzed at a central laboratory. The CK and PK values varied with age in normals: both fell with age early in life, and CK rose after the fifth decade. Discriminant analysis indicated that the combination of mean CK and PK corrected for age yielded the best data for calculation of carrier probability. Using the best model, only 45% of obligate carriers could be identified at a false-positive rate of 2.5%. Daughters of obligate carriers have a disproportionate decline in CK and PK with age as compared to noncarrier females, suggesting that the rate of carrier detection will be higher in the first two decades. Our low rate of carrier detection, as compared to other studies, may reflect both the age of our obligate carrier population and the use of a control group that is more representative of the carrier population.

Adolescent↗
PubMed1985

Plasma exchange and prednisone in Guillain-Barré syndrome: a controlled randomized trial.

A controlled randomized trial of plasma exchange combined with prednisone was compared with supportive care alone in patients with Guillain-Barré syndrome (GBS). There was no significant improvement in the treated group over the controls. The sample size, albeit small (12 treated and 13 controls), had the power (95% chance) to detect a change of 2 British Medical Research Council grades of strength between the groups. The difference in our results and others that indicated a beneficial effect of plasma exchange may reflect an adverse effect of prednisone on recovery in GBS. Failure to find a benefit of plasma exchange in our patients also raises the possibility that GBS may be a heterogeneous disorder with humoral factors playing a role in some but not all patients.

Adolescent↗
PubMed1985

Physiologic assessment of phosphoglycerate mutase deficiency: incremental exercise test.

A third case of phosphoglycerate mutase (PGAM) deficiency, a metabolic myopathy involving terminal glycolysis, was identified in a 24-year-old black man with episodic, exercise-induced myoglobinuria since age 13. To better understand the physiologic consequences of PGAM deficiency, incremental exercise testing was performed. Results were compared with those of two patients having myophosphorylase deficiency and five normals. In contrast to the patients with phosphorylase deficiency, the PGAM-deficient patient achieved near-normal levels of maximal exercise and produced a normal peak lactate after exercise. The mechanisms underlying the asymptomatic performance of such strenuous exercise in this case are uncertain, but the data suggest that unidentified factors are operative in precipitating attacks of myoglobinuria in patients with some metabolic myopathies. Despite similar clinical histories, patients with different glycolytic enzyme deficiencies can have striking differences in exercise tolerance.

Adult↗
PubMed1984

Clinical investigation in Duchenne muscular dystrophy: IV. Double-blind controlled trial of leucine.

Ninety-six patients with Duchenne muscular dystrophy (DMD) were randomized and placed either on placebo or oral leucine at a dose of 0.2 g per kg per day. Patients were evaluated using a protocol that measured muscle strength, joint contracture, functional grade and activity, and pulmonary function tests. After 1 month there was a transient but significant difference in the strength of the two groups, the treated group being stronger than the placebo group. At 6 months there was also a transient difference in joint contracture measurements. Analysis of the data showed that the difference between the groups for both these measurements could not be ascribed to a therapeutic effect of leucine but rather to an unexpected drop in the placebo group. This was recognized only because the slope of deterioration for these functions had been well documented during the natural history phase of the study. These results indicate that oral leucine failed to produce a therapeutic response over a 1-year double-blind, controlled trial.

Child↗
PubMed1983

Studies on the morphologic alterations of axonal membraneous organelles in neurofilamentous neuropathies.

Alterations in the membraneous organelles were studied in two experimental neuropathies: 2,5-hexanedione (2,5-HD) and beta,beta'-iminodiproprionitrile (IDPN), both of which exhibit massive neurofilamentous accumulation. The membranous organelles were stained using the diaminobenzidine potassium ferrocyanide (DPF) method. In 2,5-HD, where there is a progressive impairment of fast axoplasmic transport, studies of the smooth endoplasmic reticulum (SER) revealed a fragmentation and disruption of the continuity of the longitudinally oriented interconnecting tubules and a significant increase in the number of free vesicles. In IDPN, where studies of fast transport have been normal, the longitudinal orientation of the smooth SER tubules was not disturbed although channels of longitudinally oriented tubules of SER were clustered with microtubules and mitochondria. This study suggests that in 2,5-HD the accumulation of vesicles in association with fragmentation and disorganization of the SER is one of the morphologic correlates of the impaired fast anterograde transport system.

Animals↗
PubMed1983

Immunocytochemical studies of cathepsin D in human skeletal muscle.

The distribution of cathepsin D, an acidic endopeptidase, was localized by immunocytochemistry in human skeletal muscle obtained from 34 persons with a variety of neuromuscular disorders. Normal human skeletal muscle contained small amounts of cathepsin D, all of which was found close to the sarcolemmal membrane. Immunoreactive cathepsin D was present in the cytoplasm of many infiltrating phagocytic cells and was increased in skeletal muscle fibers from patients with muscular dystrophies, inflammatory myopathies, rhabdomyolysis, acid maltase deficiency, and neurogenic atrophy. In cases of Duchenne type muscular dystrophy, the increase in cathepsin D was especially prominent in small regenerating fibers, in which it was visualized at the ultrastructural level in lysosome-like organelles and extralysosomal locations. The function of cathepsin D in skeletal muscle is unclear, but the present findings suggest a possible role in muscle regeneration and repair. Such a role would necessitate careful selection of drugs which interfere with proteolytic activity if they are to be used as therapeutic agents in treating neuromuscular diseases.

Adolescent↗
PubMed1983

Clinical investigation in Duchenne dystrophy: 2. Determination of the "power" of therapeutic trials based on the natural history.

A prospective study of 114 patients with DMD provided data for "power" calculations for future therapeutic trials. There was a decline in strength of 0.4 units per year (on a 0-10 scale). Contractures of the iliotibial bands, hip flexors, and heel cords developed before 6 years. Contractures of other joints accompanied the increased use of wheelchairs. All children walked until 8 years with functional "improvement" between 3-6 years. Children of the same age varied widely in their strength, degree of contracture, and functional abilities. Fifteen percent of the patients appear to have a milder variety of the disease and are termed "outliers." To test a drug which might slow the disease to 25% of its original rate of progression, two groups (placebo and treatment) of 40 patients each would have to be followed for one year.

Adolescent↗
PubMed1983

The experimental production of Renaut bodies.

Renaut bodies are loosely-textured whorled, cell-sparse structures found in the subperineurial space of peripheral nerves. Although described in 1881, their significance is still debated. Rats were placed in wire-mesh cages for 4 days to 6 weeks and the lateral and medial plantar nerves were sequentially removed. The initial change was the presence of endoneurial edema which dissected and displaced nerve fibers producing an endoneurial cleft. With the influx of fibroblasts, these clefts became discretely separated by circumferentially oriented processes. Over time the clefts enlarged and became filled with loosely-textured amorphous and fibrillar material as well as collagen. The Renaut bodies ranged from 15 to 80 microns in diameter. In this model the Renaut bodies formed at the maximum site of compression of the lateral plantar nerve. The fibroblasts appeared to be derived from the endoneurial connective tissue and were not the result of degenerating endoneurial structures. Renaut body formation was independent of axonal degeneration. The present study strongly suggests that Renaut bodies are a response to repeated mechanical stress.

Animals↗
PubMed1983

Changes in sciatic nerve cathepsin D after ligation or exposure to neurotoxins.

The content and distribution of cathepsin D, a lysosomal acidic endopeptidase, were determined by immunochemical methods in rat sciatic nerve near the site of a ligature or after exposure of animals to neurotoxins. In normal sciatic nerve, cathepsin D was localized predominantly in the perinuclear regions of Schwann cells. In ligated nerve, cathepsin D increased equally in both the proximal and distal nerve segments adjacent to the ligature. Although orthograde and retrograde axonal transport of cathepsin D may have contributed to this increase, immunocytochemical methods indicated that Schwann cells or other phagocytic cells accounted for the bulk of the increased cathepsin D content of nerve. Axonal function was nontraumatically altered by the administration of 2,5-hexanedione, acrylamide, B,B'-iminodipropionitrile or zinc pyridinethione. Exposure to any of these neurotoxins raised cathepsin D content throughout the sciatic nerve twofold or more, and greater amounts of immunoreactive cathepsin D in the cytoplasm of Schwann cells could be demonstrated immunocytochemically. These results indicate that changes in cathepsin D content of Schwann cells may be a reflection of their catabolic activity. The increased Schwann cell cathepsin D content in toxic axonopathies is further proof for an enhanced Schwann cell role as a phagocyte resulting from axonal injury.

Animals↗
PubMed1983

Postoperative pericarditis following thymectomy for myasthenia gravis. A prospective study.

Eight consecutive patients who underwent thymectomy for the treatment of myasthenia gravis were evaluated prospectively for the development of postoperative pericarditis. In four of the eight patients (50 percent) pericarditis developed within 48 hours after thymectomy. All four had a three-component pericardial friction rub, two of the four patients had a new postoperative pericardial effusion by echocardiography, and in two typical ECG diffuse concave ST segment elevation and evolutionary ST and T wave changes developed. In the four patients with postoperative pericarditis, a malignant thymoma adherent to the pericardium was found in two, while two patients had a normal thymus histology with no adherence to the pericardium. Thus, postoperative pericarditis was found in both of the patients with a thymoma and in two of six patients without a thymoma. This study demonstrates that a high incidence of pericarditis occurs following thymectomy for the treatment of myasthenia gravis.

Adolescent↗
PubMed1981

Acrylamide and 2,5-hexanedione neuropathies: abnormal bidirectional transport rate in distal axons.

Events taking place in the distal axon including delivery, turn-around and return of labelled materials toward the cell body were examined in 2,5-hexanedione (2,5-HD) and acrylamide-induced neuropathies. Retrograde transport profiles obtained from 2,5-HD as well as acrylamide intoxicated axons demonstrated a delay in the time of onset of accumulation and a decrease in the amount of returning activity to the distal collection segment. Integral analysis of the data indicated a decrease in bidirectional transport rate within the distal axons rather than a failure in the turn-around process at the nerve terminal.

Acrylamides↗
PubMed1981

Chemical and morphological studies on garfish peripheral nerves.

Gangliosides were extracted, separated by thin layer chromatography, and quantitated in three cranial nerves of the garfish (Lepisosteus osseus): the completely unmyelinated olfactory nerve (OLF), and two nerves composed of both myelinated and unmyelinated fibers, viz., the main trunk of the maxillary nerve (MAX) and a branch of the maxillary nerve (BR-MAX). Morphological studies on each of these nerves were done to verify that the OLF had been excised free of any contamination from the accompanying myelinated BR-MAX, to aid in the interpretation of the biochemical findings, and to clarify the nature of the OLF supporting cell. The chief chemical findings were (1) documentation of the presence of gangliosides in nerves previously thought not to contain them, (2) demonstration that gangliosides can be associated with unmyelinated nerves, (3) demonstration of a greater proportion of one simple ganglioside (G-6) in the OLF but greater proportions of two complex gangliosides (G-2 and G-0) in the MAX and BR-MAX, and (4) that either GM4 or a variant of the GM3 is present in OLF. The morphological findings with respect to the difficulty of ascribing only peripheral nervous system characteristics to the OLF supporting cell are discussed in relation to the ganglioside band chromatographing slightly ahead of GM4 in the OLF.

Animals↗
PubMed1981

The spontaneously diabetic BB Wistar rat. Morphologic and physiologic studies of peripheral nerve.

The spontaneously diabetic "BB" Wistar rat was examined for evidence of peripheral nerve abnormalities by a combined morphologic and physiologic approach. The studies were done on rats kept severely hyperglycemic and frequently ketotic. The peripheral nerves of the lower extremities, including the most distal nerves of the intrinsic foot muscles, revealed only minimal abnormalities by histologic and morphometric examination. Sciatic nerve conduction studies, however, measured over a 2-month period did not show a significant slowing in diabetics compared with age-matched controls, as well as between diabetics and weight-matched controls. In addition, fast anterograde axoplasmic transport studies were correlated with serum glucose results. Rats maintained severely hyperglycemic with or without ketosis had abnormal down flow rats of [3H]leucine compared to controls. Diabetic rats maintained with normal blood glucose levels showed no change in transport rates. These results suggested that persistent hyperglycemia in the "BB" Wistar rat produces significant physiologic but not significant structural abnormalities in the peripheral nerve.

Animals↗
PubMed1980

Axoplasmic transport in zinc pyridinethione neuropathy: evidence for an abnormality in distal turn-around.

Axoplasmic transport studies were done in rats with a zinc pyridinethione-induced dying-back neuropathy characterized by the accumulation of branched interconnected tubulovesicular profiles in the motor nerve terminals. Fast anterograde transport studies in sensory and motor systems were significantly reduced compared to controls but there was a wide variation in results and a lack of correlation with clinical involvement. Retrograde transport studies showed a delay in the time of onset and a reduction in the amount of retrograde transported materials. Analysis of the integrals of retrograde transport indicated that the defect was related to a failure in the turn-around process in the distal axon as opposed to a decreased rate of retrograde transport. Similar changes were not present in the proximal morphologically normal portion of the axon where retrograde transport was provoked with a crush injury.

Animals↗
PubMed1980

Neurotonia: impulse-induced repetitive discharges in motor nerves in peripheral neuropathy.

Delayed relaxation of muscle following voluntary contraction was an unusual feature of a mild chronic sesorimotor peripheral neuropathy in an adult. This abnormality resulted from rapid repetitive discharges in motor nerves occurring only in response to passing impulses; there was no spontaneous nerve discharge. Voluntary contraction of affected muscles generated involuntary high-frequency discharges of motor unit potentials, which persisted briefly after attempted relaxation. Nerve blocks localized independent zones of hyperexcitability in distal and proximal sections of nerve from which such repetitive discharges could be triggered. Intravenous administration of phenytoin diminished the discharge. Examination of intramuscular nerve bundles revealed loss of myelinated nerve fibers with numberous sprouting and remyelinating axons. These findings, along with muscle biopsy changes of neurogenic atrophy and type grouping, strongly favor an axonal neuropathy. An explanation for the repetitive nerve discharge is slow waning of heightened excitability of a motor nerve after passage of an impulse.

Adult↗