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Biomedical subjects

M Clark

Publications and source records attributed to M Clark.

At least 253 records · Page 14Linked to original sources
PubMed1987

Intraoperative autologous transfusion during major aortic reconstructive procedures.

To evaluate the benefits and disadvantages of autologous intraoperative transfusion during major aortic reconstructive procedures, we retrospectively studied 50 patients who had major aortic revascularization procedures without the use of autologous transfusion devices (group 1) and prospectively evaluated a second 50-patient cohort having similar procedures, but with the use of the autologous transfusion device for salvaging and reinfusing lost blood. Both groups were assessed for preoperative risk factors and postoperative complications. We found a somewhat lower morbidity in the autotransfusion group and more complete replacement of blood loss. Autologous transfusion accounted for approximately 75% of all transfused blood in group 2, tremendously reducing blood bank requirements. In addition to reduction of immediate postoperative morbidity, further risks associated with homologous transfusion such as hemolysis, posttransfusion hepatitis, transfusion-related acute lung injury, anaphylaxis, and transfusion-transmitted acquired immunodeficiency syndrome (AIDS) were markedly reduced or eliminated.

Aged↗
PubMed1987

Blocking of cytotoxic T cell function by monoclonal antibodies against the CD45 antigen (T200/leukocyte-common antigen).

Cytotoxic T cells are important effectors in graft rejection and antiviral immunity. A full identification of the functional surface molecules used by these cells may help in determining the best strategies for the therapeutic control of rejection responses. Many T cell surface molecules have been implicated in cytotoxic function through the ability of specific monoclonal antibodies to inhibit T cell activity in vitro. Such measures of "inhibition" must be affected by the avidity of interaction of antibody with the particular surface molecule, as well as the avidity of that surface molecule for any physiological ligand. We show that the introduction of an antiglobulin step substantially amplifies the inhibitory effects of certain CD3 and CD8 monoclonal antibodies, presumably by conferring multivalency. In addition the "antiglobulin" approach has permitted, for the first time, the demonstration that monoclonal antibodies to the "common" determinants of the leukocyte-common antigen family (CD45/LCA/T200) prevent cytotoxic T cell function.

Animals↗
PubMed1987

Pharmacokinetics of dantrolene sodium in horses.

The pharmacokinetics of dantrolene sodium were investigated in horses following both intravenous (2 mg/kg) and intragastric (4 mg/kg) administration. Two ponies also received dantrolene sodium intravenously (2 mg/kg) in a pilot study to obtain preliminary kinetic data and to determine urinary and biliary excretion of the intact drug. Distribution and elimination of dantrolene was rapid, resulting in an elimination half-life of 129 +/- 8 (SEM) min and a whole body clearance of 4.16 +/- 0.52 ml/min/kg. Following intragastric administration, dantrolene rapidly acheived peak concentrations within 1.5 h, but was incompletely absorbed, with a bioavailability of 39 +/- 10%. Small amounts of intact drug were recovered in urine and bile. Based upon disposition kinetics of dantrolene in these studies, intravenous and intragastric dosage regimens were determined which would maintain blood dantrolene concentrations within the predicted clinically effective range.

Animals↗
PubMed1987

An autoantibody with activity dependent on red cell age in the serum of a patient with autoimmune haemolytic anaemia and a negative direct antiglobulin test.

A red cell IgM autoantibody with anti-e specificity was identified in the serum of a rhesus-negative (rr) patient presenting with haemolytic anaemia and a negative direct antiglobulin test. The autoantibody strongly agglutinated normal allogeneic rhesus-negative (rr) red cells in saline at 37 degrees C but had only weak activity for autologous red cells. Incubation of the patient's serum with subpopulations of normal allogeneic red cells obtained by density fractionation, demonstrated that the strong agglutinating activity of the autoantibody was for red cells with density greater than 1.090 g/ml. Young red cell subpopulations of lower density gave weak reactions and low titration scores equivalent to those obtained with autologous red cells during the haemolytic episode. The patient's red cells during remission however, when the patient's haemoglobin level had returned to normal, were strongly agglutinated by serum samples taken during the haemolytic episode; as was the case with normal allogeneic red cells, the strong activity was for patient red cells with density greater than 1.090 g/ml, red cell populations of lower density giving low titration scores. The findings in this case indicate that the patient's red cells which had survived haemolysis during the haemolytic episode were young red cells (density less than 1.090 g/ml), the weak sensitization of these cells being insufficient to cause their destruction by macrophages. Furthermore, these findings, together with observations that IgG autoantibodies may also bind less strongly to young red cells [Gray et al., Br. J. Haemat., 55: 335-345, 1983; Branch et al., Blood 63: 177-180, 1984].(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic, Autoimmune↗
PubMed1987

Liver function abnormalities in chronic heart failure. Influence of systemic hemodynamics.

To characterize the incidence and severity of liver function abnormalities in patients with congestive heart failure, we analyzed systemic hemodynamics and biochemical profiles in 133 patients with stable chronic congestive heart failure, secondary to a dilated cardiomyopathy. The patients were divided into three groups, based on the severity of the reduction in cardiac index (CI). The mean values of all liver function tests in groups 1 (n = 43; CI greater than or equal to 2.0 L/min/m2) and 2 (n = 48; CI greater than 1.5 and less than 2.0 L/min/m2) were essentially normal, except for minimally elevated alkaline phosphatase levels and slightly decreased albumin levels in both groups, and slight increases in levels of gamma-glutamyl transpeptidase and total bilirubin in group 2. In contrast, group 3 patients (n = 42; CI less than or equal to 1.5 L/min/m2) had the most severe heart failure, as assessed by the lowest CI and highest cardiac filling pressures, and significantly higher levels of aspartate aminotransferase (65 +/- 82 U/L), alanine aminotransferase (77 +/- 102 U/L), lactate dehydrogenase (282 +/- 91 U/L), and total bilirubin (29 +/- 14 mumol/L [1.7 +/- 0.8 mg/dL]). The percentage of patients in group 3 with these abnormalities ranged between 27% and 80%. Although linear regression analysis showed that the elevations in right atrial and pulmonary wedge pressures, and the decreases in CI, were significantly correlated with liver function abnormalities, the correlation coefficients were small. Thus, liver function abnormalities remain common in patients with congestive heart failure but are generally small in magnitude and not associated with clinically apparent hepatic disease. It is likely that reduced forward flow and passive backward congestion are both contributing factors in the pathogenesis of these biochemical abnormalities, although nonhemodynamic factors may also be important.

Adult↗
PubMed1987

Differentiation of vascular and neurogenic claudication.

Lower extremity pain caused by exercise but relieved by rest is usually a reliable symptom of chronic arterial insufficiency. However, similar discomfort often occurs in patients who have neurospinal compression. Furthermore, both arterial occlusive disease and neurogenic causes of lower extremity discomfort may present simultaneously. Forty patients with symptoms that suggested intermittent claudication comprised our study group. All had non-arterial cause of their complaint. The nonvascular origin of the symptoms was suggested initially by clinical evaluation in 30 patients and by noninvasive evaluation in 25 patients. The neurospinal origin of symptoms was obscured in 15 patients because of the concomitant presence of significant arterial occlusive disease as demonstrated by noninvasive arterial testing. Twelve of these 15 patients underwent arterial reconstruction, which did not relieve their symptoms. Subsequently, the neurospinal origin of their symptoms was proven by appropriate evaluation and therapy. Forms of evaluation that proved helpful in the differential diagnosis were lumbosacral spine x-rays, electromyography, nerve conduction velocity studies, computerized tomography, Doppler noninvasive assessment and, at times arteriography and contrast myelography.

Adult↗
PubMed1986

AIDS in the workplace.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1986

A new case of high-molecular-weight kininogen inherited deficiency.

A preoperative hemostasis study discovered a prolonged activated partial thromboplastin time in a 23-year-old Portuguese Caucasian woman without personal or past family history of hemorrhage or thrombosis. This was corrected by pooled plasma that excluded circulating anticoagulant. Activated partial thromboplastin time was prolonged whatever the activator, particularly ellagic acid, and was not corrected by prolonged kaolin incubation. Levels of factors VIII and XII were normal; factor XI and prekallikrein levels were either moderately low or normal according to activators and defective reagents used. High-molecular-weight kininogen (HMWK) level assessed by coagulation and immunological method was virtually nil. Fibrinolysis activity was normal before and after venous occlusion. The programmed operation was performed without any particular preparation and no complication arose. Family investigation found heterozygous HMWK deficiency in the proposita's father and three of her siblings.

Adult↗
PubMed1986

Clostridium difficile cytotoxin inhibits protein synthesis in fibroblasts and intestinal mucosa.

The pathophysiology of Clostridium difficile colitis is thought to be mediated by release of toxin A, an enterotoxin, and toxin B, a cytotoxin. We compared the differential effects of toxin B on protein synthesis in IMR-90 fibroblasts and in hamster esophagus, stomach, gallbladder, small intestine, and cecum in organ culture. Toxin B in low concentrations stimulated (p less than 0.001) incorporation of [3H]leucine into fibroblast proteins, whereas at higher dosages it inhibited incorporation (p less than 0.001). This biphasic effect was independent of cell rounding and was not caused by a change in uptake of precursor. Purified toxin B had no effect on protein synthesis in a cell-free rabbit reticulocyte translation system, indicating that inhibition of protein synthesis in intact fibroblast monolayers and intestinal explants is a consequence of toxin B effect on some other cellular target. Toxin B significantly inhibited protein synthesis in hamster cecal explants in a dose-dependent fashion. Again, this inhibition was not mediated by altered precursor uptake. Toxin B significantly inhibited in vitro protein synthesis in hamster terminal ileum, cecum, and sigmoid colon, but not in esophagus, gallbladder, stomach, or duodenum. These results suggest that toxin B-mediated inhibition of protein synthesis may be a generalized toxic effect in tissue culture cells and intestinal epithelium. Inhibition of protein synthesis in the distal intestinal epithelium may contribute to the pathophysiology of colitis caused by this organism.

Cecum↗
PubMed1986

Correlation of mononuclear phagocyte assay results and in vivo haemolytic rate in subjects with a positive direct antiglobulin test.

A mononuclear phagocyte assay has been used to measure the in vitro interaction of normal donor monocytes with the red cells from subjects with a positive direct antiglobulin test (DAT). The relationship between the in vivo haemolytic rate in these subjects and the results obtained in the assay, expressed as the number of red cells associated with 100 monocytes (ARC value), has been examined. From the results of assays in which normal donor monocytes were incubated with normal (DAT negative) donor red cells it was calculated that ARC values of greater than 2 could be considered significantly elevated. Assays performed on 24 patients with a positive DAT and warm autoimmune haemolytic anaemia resulted in a mean ARC value of 42 (range 1-212). Assay results for two of the patients in this group, however, were not significantly elevated from normal. The red cells from three patients with a negative DAT who were suspected of having autoimmune haemolytic anaemia showed no association with normal donor monocytes in the assay. The mean ARC value obtained for 14 non-haemolysing subjects with a positive DAT was 7 (range 1-47). Assay results for only 10 of the 14 subjects in this non-haemolysing group fell within the normal range. The correlation of assay results and in vivo haemolysis was strengthened when the assays were performed with autologous monocytes. A possible explanation for the unexpectedly low ARC values obtained in some cases of autoimmune haemolytic anaemia is discussed.

Anemia, Hemolytic, Autoimmune↗
PubMed1986

Immune haemolysis in a renal transplant recipient due to antibodies with anti-c specificity.

A 55-year-old man received a cadaver kidney from a donor whose serum contained red cell antibodies with anti-c specificity. Atypical antibodies were shown to be absent from the recipient's red cells and serum at the time of transplant. Blood was not transfused during surgery. Two weeks after the transplant, the recipient developed a positive direct antiglobulin test due to antibodies with anti-c specificity. Immune haemolysis was diagnosed in the patient 3 weeks after transplant. The possible mechanisms involved in antibody formation in the recipient are discussed.

Antibody Specificity↗
PubMed1986

Reduced survival of isotope-labelled Rh(D)-negative donor red cells in a patient with anti-LWab.

The serum of an 85-year-old Caucasian male with no history of blood transfusion contained an IgG3 antibody with anti-LWab specificity. The antibody failed to react with dithiothreitol-treated red cells, and there was a marked reduction in titre of the antibody with pronase-treated cells, findings consistent with an antibody having this specificity. High association values were obtained in a mononuclear phagocyte assay when LW-positive red cells, sensitised in vitro with the patient's serum antibody, were incubated with peripheral blood monocytes from the patient. In vivo red cell survival studies demonstrated that 99mTc-labelled rhesus-negative (rr), LW-positive red cells had 53% survival at 1 h. The IgG subclass of the antibody, mononuclear phagocyte assay results and in vivo survival studies predicted a significant reduction in the posttransfusion survival of therapeutic volumes of rhesus-negative (rr), LW-positive red cells.

Aged↗