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Biomedical subjects

D Grob

Publications and source records attributed to D Grob.

At least 145 records · Page 8Linked to original sources
PubMed1981

Desensitization to acetylcholine at motor end plates in normal humans, patients with myasthenia gravis, and experimental models of myasthenia gravis.

Desensitization to ionophoretically applied ACh at the motor end plates of normal humans and patients with MG was studied. The pattern of desensitization at the normal human motor end plate was completely consistent with that observed in muscles of various animals. At motor end plates of MG patients there was greater desensitization and slower recovery from desensitization than in normals. A similar pattern of desensitization was observed at normal end plates when they were exposed to serum globulins of MG patients, and at end plates of muscles from mice than were repeatedly injected with serum globulins of MG patients. Despite the reported reduction in the number of ACh receptors, our calculations show that there is a large pool of spare receptors forming a sizeable margin of safety at the end plates of MG patients. The number of receptors may not show additional progressive reduction in number during repetitive motor activity. Our results indicate that desensitization could play a significant role in the development of neuromuscular block following repetitive motor activity in MG patients. The mechanism by which desensitization is augmented in MG patients in not yet clear.

Acetylcholine↗
PubMed1980

Ophthalmoplegia, ptosis, and miosis in temporal arteritis.

Ophthalmoplegia occurred in 7 of 14 patients with biopsy proved temporal arteritis. Only one patient had diplopia. In six of the seven patients, the pattern of ophthalmoplegia did not conform to the distribution of one of the ocular motor nerves. Impairment of upward gaze was most common. In five patients the ophthalmoplegia was accompanied by ptosis, and in five it was accompanied by a miotic pupil. Ophthalmoplegia and ptosis were the major manifestations of temporal arteritis in one patient. Oculomotor signs and symptoms responded to corticosteroid therapy in all seven patients, but in two patients prolonged therapy was necessary. Ophthalmoplegia or ptosis may be early manifestations and may precede visual loss, so that frequent examination is recommended in patients suspected of temporal arteritis, with prompt administration of adequate doses of corticosteroid as soon as any ocular manifestations of temporal arteritis are noted.

Aged↗
PubMed1978

Inhibition of growth of mouse ehrlich ascites by normal tissue extracts.

A dialyzable component from the aqueous extracts of mouse skeletal muscle and liver inhibited in vitro growth of a mouse Ehrlich ascites. A similar component was not detected in extracts of spleen, kidney, lung, skin, serum or small intestine. The muscle component appeared to be different from that of the liver in its resistance to heat and its stability in the culture medium. Both components however were stable on storage at 4, 23 and 37 degrees C for 72 h. Intraperitoneal injection of the muscle and liver component into mice previously innoculated with Ehrlich ascites significantly decreased tumor incidence in these animals as compared with the control.

Animals↗
PubMed1976

Characteristics and mechanism of neuromuscular block in myasthenia gravis.

The neuromuscular block of myasthenia gravis has the characteristics of an antidepolarizing (competitive block), similar to that produced by d-tubocurarine in normal subjects: progressive decrease in muscle action potentials evoked by two or more nerve stimuli, posttetanic facilitation, posttetanic fatigue, inhibition of the depolarizing action of acetylcholine (ACh) or anticholinesterase compounds, and reversal of the block by ACh or anticholinesterase compounds. In myasthenic patients spontaneously recurring negative discharges were more difficult to locate in the end-plate zone than in normal subjects, suggesting that the number or density of functioning end plates may be reduced. The threshold dose of intra-arterial ACh that increased electrical activity was higher than in normal subjects; the duration of the increased electrical activity was briefer, and was followed by more depression of negative discharges than in normal subjects and by a greater increase in the threshold dose of ACh. These results indicate that the end-plate zone of myasthenic patients is less responsive than that of normal subjects to the excitatory action of ACh, and may be more readily desensitized by ACh. In both myasthenic patients and normal subjects the intra-arterial injection of ACh produced a prompt transient decrease in evoked potentials, attributable to depolarization of the end plates, followed by recovery (and in myasthenic patients by repair), and then by a more prolonged late decrease in evoked potentials, attributable to desensitization of the end plates to transmitter. This prompt depressant effect of ACh on evoked potentials was less in myasthenic patients than in normal subjects, and the late depressant effect of ACh was greater. In myasthenic patients the late block produced by ACh had the characteristics of an antidepolarizing (competitive) type of block, including inhibition of the depolarizing action of ACh and reversibility by ACh or neostigmine, while in normal subjects the characteristics were those of a depolarizing (noncompetitive) type of block, including little or no inhibition of the depolarizing action of ACh and lack of reversal by ACh or neostigmine. The differences between the late depressant action of ACh in myasthenic patients and normal subjects resembled differences in the effect of other depolarizing compounds, such as choline, succinylcholine, and decamethonium, and are best explained by differences in behavior of the postsynaptic receptor. The disease appears to be due to the presence of abnormal forms of receptor or to abnormal responses of receptor to the transmitter. The predominance of one or other form of receptor may determine the clinical state of the myasthenic patient and his response to anticholinesterase medication.

Acetylcholine↗
PubMed1976

The role of humoral and cellular immune factors in neuromuscular block in myasthenia gravis.

The neuromuscular block of myasthenia gravis appears to be due to decreased and abnormal responsiveness of the motor end plates to transmitter, and perhaps a decreased number of functioning end plates. The presence in myasthenic patients of serum globulins that bind to a bariety of cellular and subcellular components, and of thymic abnormalities, has encourage the search for humoral and cellular immune factors that may be responsible for the anatomic and functional defects. Attempts to demonstrate neuromuscular blocking activity in the serum have been inconclusive. While 30% to 48% of myasthenic patients have globulins that react with muscle membrane, striations, ribonucleporotein, and thymic epithelial cells, these globulins have not been shown to react with the end plate or acetylcholine receptor, or to impair neuromuscular transmission. Antinuclear, rheumatoid, antimitochondrial antithyroid, anti-smooth-muscle, and anti-gastric-parietal cell factors are found in the serum of 3% to 16% of myasthenic patients, but these are much more commonly present in other diseases. However, antibodies to acetylcholine receptor from electric tissue, which were recently reported in the serum of three fourths of myasthenic patients, may prove to be more directly related to the neuromuscular block. While the majority of myasthenic patients have thymic abnormalities, including thymoma in 9% of patients and hyperplastic thymus in 66% of patients, the remaining 25% of patients have normal, involuted, or undetectable thymus. Thymectomy has a favorable effect in about two thirds of myasthenic patients, but about one third of patients have no benefit. Thirty-two patients have been described who developed myasthenia gravis after total thymectomy and presumably in the absence of the thymus. Thymus lymphocytes of myasthenic patients have some differences from those of normal subjects, including a greater proportion of B cells, but their significance is not known. Attempts to demonstrate neuromuscular blocking activity in the thymus of myasthenic patients have been inconclusive. Blood lymphocytes of myasthenic patients also have some differences from those of normal subjects, including a lower proportion of T cells. The proportion of both T and B cells increased following thymectomy. While studies on the immunological reactivity of lymphocytes from myasthenic patients have shown some differences from those of normal subjects, neuromuscular blocking activity has not been demonstrated in these cells or in their extracts. There is increasing evidence that the neuromuscular block of myasthenia gravis is due to alteration of the acetylcholine receptor. The recent reports of antibodies to acetylcholine receptor in the serum of myasthenic patients suggests that these may be responsible for the neuromuscular block, but such action, and the cause of antibody release, remain to be determined.

Animals↗
PubMed1976

Corticotropin and corticosteroids in generalized myasthenia gravis: comparative studies and role in management.

The effect of 310 courses of corticotropin, methylprednisolone, prednisone, and dexamethasone were studied in 62 patients with generalized myasthenia gravis who were poorly responsive to anticholinesterase medication and most of whom required assisted respiration. Improvement in strength and response to anticholinesterase medication occurred in 91% of the courses, and was moderate or marked in 63%. The incidence, degree, and duration of improvement appeared to be dose related. High doses of dexamethasone (20 mg orally each day for 10 days, repeated if necessary), which had 75% more glucocorticoid effect than any other regimen studied, produced the highest incidence of both improvement (100%) and moderate-to-marked improvement (75%), and the greatest duration of improvement (more than 3 months after 40% of the courses). The duration of improvement following intensive courses of any of the corticosteroids was approximately doubled by the subsequent administration of smaller doses of dexamethasone or prednisone on alternate days. Most patients with severe disease relapsed after 3 to 6 months of corticosteroid treatment, but increase in the dose of corticosteroid, and daily administration, which was more effective than alternate-day administratin, almost always again resulted in improvement. Corticotropin and corticosteroids were equally effective before and after thymectomy. High doses of corticotropin and corticosteroid produced an initial exacerbation of the disease in 80% of the courses, which was moderate or marked in 57%. Reduction in dose reduced the incidence of severe exacerbation, but did not prevent it, and also resulted in slower and less marked improvement. Withholding anticholinesterase medication did not prevent exacerbation or increase improvement, and afforded no advantage, though it was usually helpful to reduce the dose of this medication. Because of the hazard of initial exacerbation and the occurrence of other serious side effects in 15% of the patients. (bleeding ulcer, vertebral compression, aseptic necrosis of the femoral head or tibia, and subcapsular cataracts), it is recommended that corticosteroid treatment be limited to myasthenic patients who are not responding satifactorily to anticholinesterase medication, that smaller doses be employed in patients whose disease is not life threatening, and that higher doses be reserved for patients who are critically ill and are being managed, at least initially, in an intensive care unit.

Adolescent↗