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Biomedical subjects

J T Sharp

Publications and source records attributed to J T Sharp.

At least 37 records · Page 2Linked to original sources

Compliances of human rib cage and diaphragm-abdomen pathways in relaxed versus paralyzed states.

The respiratory magnetometer method of Konno and Mead was used to measure separately the rib cage and the diaphragm-abdomen components of the total respiratory system compliance in 11 subjects with normal respiratory systems. Measurements made in the awake, relaxed state by the method of Heaf and Prime were compared with similar measurements made in the anesthetized, paralyzed state by the supersyringe method. The rib cage component was greater in the paralyzed than the relaxed state in 9 of 11 subjects, but the diaphragm-abdomen component was greater in the relaxed than the paralyzed state in 8 of 11 subjects. We believe that these differences can be explained by respiratory muscle activity in the presumed relaxed state. The fraction of the tidal volume attributable to rib cage displacement compared to abdominal displacement was greater during mechanical ventilation in the paralyzed state than during awake, spontaneous breathing. This can be explained by the different distribution of inflating forces produced by diaphragmatic contraction compared to positive airway and alveolar pressure, in particular by the very different patterns of diaphragmatic displacement in the 2 states.

Abdomen

Multicenter comparison of naproxen and indomethacin in rheumatoid arthritis.

In a double-blind, crossover study, naproxen, 250 mg twice a day, naproxen, 500 mg taken at bedtime, and indomethacin, 25 mg four times a day, were compared in 132 patients with rheumatoid arthritis; six centers participated in the study. Objective indices of arthritis activity, such as number of clinically active joints, walking time, and duration of morning stiffness, were nearly identical for the three treatment regimens. Of particular interest was the observation that efficacy of a single daily dose of naproxen was comparable to that of the twice-daily dosage. Naproxen was better tolerated than indomethacin, as shown by a statistically significant difference in the incidence of CNS complaints.

Adult

Relationship between multicentric reticulohistiocytosis and tuberculosis.

Some cases presently classified as multicentric reticulohistiocytosis may represent unusual manifestations of tuberculosis. Antituberculous chemotherapy may be justified in patients who have clinical and histopathologic evidence of multicentric reticulohistiocytosis in association with a positive tuberculin skin test.

Arthritis

Effect of plasma exchange on circulating immune complexes and antibody formation in patients treated with cyclophosphamide and prednisone.

A patient with systemic lupus erythematosus (SLE) and a patient with an immune complex disease resembling Goodpasture's syndrome were treated with cyclophosphamide, prednisone and repeated plasma exchanges. Circulating immune complexes decreased, and symptoms of central nervous system disease remitted for up to 15 to 20 days after plasma exchange in the patient with SLE. In vitro lymphocyte blastogenic responses to antigens were also transiently increased on two occasions following treatment. In the second patient, decreases in circulating immune complexes and clinical improvement were ascribed chiefly to immunosuppressive drug treatment. Serum antibody to keyhole limpet hemocyanin was relatively unaffected by plasma exchange in both patients. These results suggest that plasma exchange may help to deplete circulating immune complexes or alter the equilibrium between soluble antigen and antibody which causes complexes to form and circulate. It may be less effective in reducing circulating antibody levels in patients who continue to produce new antibody.

Adult

Cell-mediated immunity in rheumatoid arthritis.

Cell-mediated immunity in rheumatoid arthritis (RA) was assessed by skin testing with six antigens in 107 patients, 94 of whom were age, sex, and race-matched with healthy individuals or patients with diseases unrelated to immunological abnormalities. 20% of RA patients were anergic. Impaired cell-mediated immunity in the RA patients was manifested by a decrease in the magnitude of skin reactivity as well as a decrease in the incidence of positive reactions to multiple antigens. Depression in cell-mediated immunity was related to age but not to sex, duration of disease, or disease activity. A slight correlation was found between absolute peripheral lymphocyte counts and the number of positive skin tests, and was confirmed by finding an association between lymphocyte counts and the size of skin reactions. A correlation was also found between lymphocyte counts and disease activity. Four explanations of the observed depression in cell-mediated immunity in RA were considered: (1) a preoccupation of the immune mechanism of the host with cell-mediated immunity reactions related to the pathogenesis of the disease; (2) a depression of cell-mediated immune reactivity by a virus infection; (3) depression of cell-mediated immunity by therapy; and (4) immune complex suppression of cell-mediated immunity. No effect of gold therapy was found. The near universal use of salicylates or other anti-inflammatory drugs did not permit investigation of the effect of these drugs on cell-mediated immunity.

Adult

Thoracoabdominal motion in chronic obstructive pulmonary disease.

Studies of thoracoabdominal motion using the respiratory magnetometer were performed in 30 patients with chronic obstructive pulmonary disease. Volume equivalency of thoracic and abdominal deflections was established by using the concepts and methods developed by Konno and Mead. Twenty patients were ambulatory, although disabled, and 10 were in acute respiratory failure and were studied in a respiratory intensive care unit. Five of 20 ambulatory patients and 8 of 10 patients in acute respiratory failure showed inward abdominal motion coincident with outward rib cage motion during inspiration, suggesting ineffective diaphragmatic function. This pattern of thoracoabdominal motion was identical to that seen in 2 high quadriplegics with diaphragmatic paralysis when they were breathing entirely with their neck muscles. Inspiratory ascent of the diaphragm was confirmed fluoroscopically in 3 of the 5 ambulatory patients. Patients showing this pattern were generally severely disabled and had the largest residual volumes. Two abnormal patterns of thoracoabdominal motion were observed during the performance of maximal voluntary ventilation in the ambulatory patients. The first, seen in 9 of 20 patients, was characterized by reciprocal or paradoxical motion of rib cage and abdomen, with increase in rib cage volume associated with decrease in abdominal volume during inspiration. The second pattern, seen in 5 of 20 patients, showed complete disorganization of rib cage and abdominal motion, with no consistent or reproducible pattern. Thus, a significant proportion of patients with disabling chronic obstructive pulmonary disease show abnormalities in thoracoabdominal motion that are observable with the respiratory magnetometer and ofter by simple inspection. Most of these abnormalities suggest malfunction of respiratory muscles, particularly the diaphragm.

Abdomen

Polyarthritis, polyarteritis and hepatitis B.

An association between viral hepatitis and two rheumatic disease syndromes has been observed. Twenty-nine patients manifested a transient polyarthritis, sometimes associated with a rash (Group I). Ten patients were seen with a multisystem disease (Group II). Histologic evidence of arteritis or glomerulonephritis was present in seven of ten patients with multisystem disease. Liver tissue from 18 patients showed morphologic evidence of hepatitis with viral features in 9 of 10 patients in Group I and in 6 of 8 patients in Group II. Hepatitis B surface antigen (HBsAg) and/or antibody to HBsAg were detected in sera of all 39 patients. Abnormal liver functions were present in 36. Twelve Group I patients and 2 Group II patients became jaundiced. Rheumatoid factor was present in sera of seven patients in each group. The third component of complement (C3) was depressed in 13 patients in Group I and 7 patients in Group II. The fourth component of complement (C4) was decreased in 8 of 21 Group I and 3 of 7 Group II patients. Synovial fluid C3 was decreased in 2 of 11 Group I and 1 of 4 Group II patient's fluids. Articular inflammation in patients with transient polyarthritis responded in three to seven days to aspirin, acetominophen and/or bedrest alone and rashes disappeared spontaneously. Patients with multisystem disease generally had a prolonged illness and responded somewhat unpredictably to prednisone or a combination of prednisone and cyclophosphamide.

Adolescent

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