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Biomedical subjects

J T Sharp

Publications and source records attributed to J T Sharp.

At least 91 records · Page 5Linked to original sources

Mechanics of the canine diaphragm.

Diaphragmatic force-length behavior was assessed in anesthetized dogs using two techniques. One employed measurements in a diaphragm strip with intact nerve and blood supply; the second related transdiaphragmatic pressure (Pdi) to direct estimates of diaphragmatic tension from strain gauge arches during bilateral, tetanic, supramaximal phrenic nerve stimulation. In strip preparations the diaphragm exerted active force at lengths as short as 40% of resting in situ length (Lo), and maximal force was registered at a length averaging 25% greater than Lo. This suggested a broader effective length range for the diaphragm as compared to other skeletal muscles. In the intact preparation both Pdi and directly measured diaphragmatic tension were inversely related to lung volume and when they were used to calculate the diaphragm's effective radius of curvature (r), r was found to change little or decrease at large lung volumes rather than increase as theory would predict. These findings suggest that length tension characteristics outweigh geometric considerations in explaining the diaphragm's function in normal dogs and probably normal men.

Animals

The cytotoxicity of leukocytes and lymphocytes from patients with rheumatoid arthritis for synovial cells.

Unseparated peripheral blood leukocytes obtained from patients with rheumatoid arthritis (RA) were cytotoxic for synovial cells. The cytotoxic reactions produced by RA leukocytes were more frequent and of greater magnitude than cytotoxicity induced by leukocytes from normal persons and patients with other diseases, primarily connective tissue diseases. Furthermore, the cytotoxic activity of RA leukocytes was greater for RA synovial cells than for nonrheumatoid synovial cells, in contrast to the cytotoxicity of other leukocytes, which did not discriminate between synovial cells according to their origin. Tests with purified lymphocytes showed that the cytotoxicity of unseparated leukocytes directed against RA synovial cells was due to lymphocyte cytotoxicity. These data are consistent with the possibility that sensitized lymphocytes from patients with RA recognize a distinctive antigen present on rheumatoid synovial cells.

Antigen-Antibody Reactions

Treatment of Goodpasture syndrome with cyclophosphamide, prednisone and plasma exchange transfusions.

Repeated plasm exchanges were performed in a 44-year-old man with Goodpasture syndrome, also treated with cyclophosphamide and prednisone. Improvement was observed within 3 weeks of starting the protocol, and by the 76th week, endogenous creatinine clearance had increased from 30 to 56 ml/min/1.73 M2 and serum albumin from 2.7 to 3.7 g/dl. Prior treatment with immunosuppressive drugs had not significantly influenced circulating antibody levels. But sustained suppression of antibody was achieved after the plasma exchanges were begun, suggesting that physical removal of circulating antibody combined with antiproliferative drug treatment may be a useful way to control undesirable humoral immune responses.

Adult

Relative contributions of rib cage and abdomen to breathing in normal subjects.

By use of the method of Konno and Mead and the respiratory magnetometer, the partition of respired gas volumes into rib cage and diaphragm-abdomen components was accomplished in 81 normal subjects including 32 young and middle-aged men, 29 young and middle-aged women, and 20 elderly men. Studied were isovolume maneuvers and the relaxation configuration over the inspiratory capacity range, quiet tidal breathing, increased amplitudes of slow breathing, rapid inspirations and expirations, and both quiet and forceful phonation. No major differences were noted between men and women or between the young and the elderly during any respiratory acts. During quiet breathing most normal subjects are abdominal breathers when supine and thoracic breathers when upright. Rapid respiratory maneuvers were accomplished mostly through rib cage displacement suggesting that rib cage muscles are capable of more rapid action than diaphragm and abdominal muscles. Data from deep breathing and rapid maneuvers supported the view that abdominal and rib cage muscles often act to optimize the mechanical (length-tension) advantage of the diaphragm.

Abdomen

Antiglobulins and glomerulonephritis. Classification of patients by the reactivity of their sera and renal tissue with aggregated and native human IgG.

Renal biopsies and sera from 41 consecutive patients were studied to determine if antiglobulins were found more frequently in patients with severely diseased glomeruli. Patients were classified into three groups: A, 12 patients with normal renal function and minimal histological evidence of glomerular disease; B, 18 patients with normal renal function but distinctly abnormal biopsies (16 cases) or proteinuria greater than 16 g/24 h (2 cases); and C, 11 patients with both decreased function and abnormal histology. Positive latex fixation tests for rheumatoid factor were found in none of group A, four (22%) of group B, and five (45%) of group C patients. Sera heated 56 degrees C for 30 min contained precipitins reactive with heat-aggregated IgG in none of seven group A, five of ten (50%) group B, and four of ten (40%) group C patients. The quantity of 135I-labeled patient globulin which bound to immunoadsorbents coated with Cohn fraction II in competition with an equal quantity of 131I-labeled globulin from pooled plasma of normal donors was also measured. Patient globulins bound in significantly greater quantity (greater than or equal 2 SD) than the control in none of the group A, 7 of 18 (39%) group B, and 7 of 11 (64%) group C patients. Renal biopsies from 18 patients were also studied for the ability to fix fluorescein-conjugated heat-aggregated and native human IgG. None of nine tissue specimens from group A or B patients fixed either fluorescein-conjugated protein whereas tissue from eight of nine group C patients showed glomerular localization of one or both reagents. Severity of disease as judged by renal function and glomerular histology correlated with the presence of tissue-fixed and serum antiglobulins. Thus, detection of antiglobulins in glomeruli and sera of patients with glomerulonephritis may indicate a relatively poor prognosis and raises the possibility that antiglobulins may be implicated in some way in the pathophysiology of human glomerulonephritis.

Adolescent

Transverse myelopathy in systemic lupus erythematosus. Report of three cases and review of the literature.

Three cases of transverse myelopathy associated with systemic lupus erythematosus were reported, and 23 similar cases previously reported were reviewed. A diagnosis of systemic lupus erythematosus was made in only 60% before the onset of transverse myelopathy. The time of onset of myelopathy was randomly distributed during the disease. The most common presenting neurologic symptom was numbness, or weakness of the legs, or both. A unique association between the acute stage of transverse myelopathy and marked reduction of cerebrospinal fluid glucose concentration was observed. Thirteen patients died, 9 had permanent neurologic deficits, and only 4 recovered nearly normal function. Eight patients had ischemic necrosis of the spinal cord at postmortem examination, and vascular lesions were found in the spinal cord of 3 additional patients. The value of steroid treatment was uncertain. Patients who were started on steroid therapy within 24 hours of the onset of myelopathy may have benefited.

Adult