Muscles undergoing physiological adaptation to stress take up gallium-67 citrate.
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Biomedical subjects
Publications and source records attributed to H L Messmore.
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The field of coagulation testing has undergone some major technological and conceptual developments, which are briefly reviewed here. The assessment of coagulation parameters is no longer restricted to the study of clot formation and its dissolution. The understanding of the biochemical nature of coagulation processes, coupled with the development of new therapeutic agents in the treatment of hemostatic disorders, has brought about the development of fast, reliable, and clearly defined laboratory test procedures to evaluate the components of this system. The introduction of methods involving synthetic substrates has been very significant because many of the coagulation parameters can now be measured with a spectrophotometer or fluorometer, by methods that lend themselves to the automation found in most large clinical chemistry laboratories. In our laboratory, we use automated synthetic-substrate methods for antithrombin-III, plasminogen, and prothrombin, and are developing the synthetic-substrate assay equivalent of clot-based prothrombin time and partial thromboplastin. Immunological methods such as laser/rate nephelometry, enzyme-linked immunoassays, electroimmunodiffusion, and radioimmunoassays have been utilized to evaluate coagulation proteins. The relation of functional and immunological properties of these proteins to their physiological function is being studied. In coming years the testing of coagulation function will undergo some major changes and will require input from clinical chemists and other laboratory scientists to facilitate the technology transfer and proper standardization of new methods.
The carbonyl terminal tripeptide sequence of bradykinin (Pro-Phe-Arg) is molecularly manipulated to obtain agents with potent antagonistic activity towards the smooth muscle contractile activity of bradykinin. Screening of various peptide derivatives revealed that heptyl amides or esters of H-D-Pro-Phe-Arg, and H-D-Phe-Phe-Arg possessed relatively stronger antibradykinin activity on the isolated smooth muscle preparation. The parent tripeptides, H-D-Pro-Phe-Arg-OH, and H-D-Phe-Phe-Arg-OH, and their amino acid components, i.e. D-Proline, D-Phenylalanine, L-Phenylalanine and Arginine, did not possess any antibradykinin activity in concentrations of up to 10(-4) M. When the heptyl derivatives of these peptides were incubated with either heparinized or citrated whole blood or plasma, the antibradykinin activity was not lost. Incubation of these peptide derivatives with either carboxypeptidase A or B did not result in any loss of the pharmacological effect. However, pancreatic protease extract produced a significant loss of the anti-oxytocic action on the isolated rat uterus preparation. H-D-Pro-Phe-Arg-NH-lauryl derivative also blocked the action of bradykinin and this effect sustained for a longer period of time comparative to the blockade with H-D-Pro-Phe-Arg-NH-heptyl derivative. In concentrations of 10(-7) M and 10(-8) M and 1 min incubation, which blocked the contractile action of bradykinin (1 nmole) on the isolated guinea pig ileum, these peptide derivatives did not block the action of acetylcholine, histamine, and serotonin. However, in concentrations of about 10(-6) M and higher with 5 min. incubation histamin is also blocked. On the isolated rat uterus preparation the contractile action of acetylcholine, angiotensin, oxytocin and vasopressin was blocked at concentrations of 10(-6) M. These findings warrant a differential pharmacological evaluation and in vivo testing of these peptide derivatives to investigate their therapeutic potential.
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A primate model was developed to study sequential blood-vascular responses, primarily of the lung and liver, and hematologic changes during prolonged endotoxemia with or without glucocorticoid treatment. In this model, pairs of animals, one with intermittent glucocorticoid regimen, were continuously infused with endotoxin throughout the experimental period. The duration of the experiment and the onset of progressive shock could be adjusted by changing the rate of endotoxin infusion. Endotoxemia at a rate of 10 mg. per kg. per hour resulted in progressive shick which was significantly delayed with glucocorticoid treatment. Endotoxin-induced hematologic alterations included early leukopenia and gradual development of disseminated intravascular coagulation. Morphologic studies revealed margination of neutrophils and mononuclear cells in the microcirculation of lung and liver. These changes were associated with sustained phagocytosis of endotoxin by the sequestered leukocytes and Kupffer cells, degranulation of the hepatic sinusoids and spaces of Disse contained extensive fibrinous deposits which in advanced stages of shock were accompanied by midzonal and centrilobular necrosis. Pulmonary lesions included margination, degranulation and fragmentation of leukocytes, early appearance of fibrin in hepatic sinusoids, and rapid development of disseminated intravascular coagulation, endothelial damage and associated lesions of lung and liver. The results indicate that events relating to sustained phagocytosis of endotoxin by the marginating leukocytes initiate a state of intravascular inflammation with disseminated intravascular coagulation and play a vasic role in the pathogenesis of pulmonary and hepatic lesions during prolonged endotoxemia leading to shock. The findings also suggest that glucocorticoid treatment attenuates endotoxin-induced blood-vascular reactions thereby providing an early protection against the development of shock and structural damage to the lung and liver.
Non-dividing lymphocytes from patients with chronic lymphocytic leukaemia were more sensitive than normal lymphocytes to reagents as prednisolone, cytarabine, vincristine and colchicine. The maximum difference was obtained when the cells were incubated with colchicine at 37 degrees C for 20 h. The sensitivity was measured by a 'sensitivity index' which was an estimate of the average percentage of lymphocytes killed by 1.0 and 0.1 mug/ml of colchicine. The index was 0-15% for lymphocytes from the blood of 14 normal persons and was 61-98% for 23 of 25 leukaemic patients with absolute lymphocyte counts of 8,000 X 10(9)/l or more. 3 of 4 untreated patients with presumptive diagnoses of early leukaemia had low absolute counts of 3,300 to 7,600 X 10(9) lymphocytes/l and high sensitivity indices of 41 to 83%. Tests on treated patients with lymphocytes counts less than 8,000 X 10(9)/l suggested a correlation of the index with remission and relapse. Hairy cells from 3 patients with hairy cell leukaemia were resistant to colchicine. Sensitivity to colchicine seemed useful at a test for leukaemic lymphocytes and as an aid in the haematologic evaluation of patients with chronic lymphocytic leukaemia and malignant lymphoma.
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Several nonionic experimental contrast media (CM) were evaluated for their effects on coagulation cascade, platelet aggregation, and the activation of complement pathways. In an in vitro system, most of the contrast media tested showed a mild anticoagulant property by prolonging the clotting times, such as partial thromboplastin time and the thrombin time of pooled normal human plasma. However, aggregation of normal human platelets by adenosine-diphosphate (ADP), collagen, epinephrine, ristocetin, and thrombin was not blocked when the platelet-rich plasma was incubated with these agents. No quantitative or qualitative changes in the complement components C3 or C4 were detected when a mixture of CM and pooled normal human serum was analyzed by radial immunodiffusion, immuno- or crossed-immunoelectrophoresis techniques. These results indicate that nonionic contrast media produce certain transient hematologic changes and should be further tested for their immunologic properties in order to establish their absolute safety in diagnostic procedures.
The clinical and immunologic data in a case of rheumatoid arthritis complicated by serum hyperviscosity are reported. The elevation in the serum viscosity was accompanied by the presence of intermediate immune complexes which were partially purified from the patient's serum by gel filtration chromatography. These complexes had a molecular weight of approximately 510,000 daltons and contained polyclonal IgG and IgA immunoglobulins. The hyperviscosity syndrome in this patient was likely due to the presence of intermediate complexes and unrelated to the rheumatoid factor activity which was found predominantly within the IgM fraction of the serum. This case demonstrates that the hyperviscosity syndrome may, in rare cases, develop as a complication of rheumatoid arthritis. It is important to consider this possibility before the clinical symptoms of increased serum viscosity become manifest.
A case of a 40 year-old woman with Hodgkin's disease who developed acute non-lymphocytic leukemia (ANLL) accompanied by several abnormal chromosomal findings is illustrated. A very unusual coincidental finding was the coexistence of Hodgkin's lymphoma and ANLL in the same lymph node.
The antiplatelet action of intravascular contrast media (CM) Renografin-76 (diatrizoate meglumine and diatrizoate sodium) was studied in vitro and in 21 patients undergoing radiodiagnostic procedures. In vitro studies suggested that in Renografin-76, meglumine was the chief constituent responsible for its antiplatelet action. In post-CM plasma from patients, clotting times were prolonged and platelet aggregation greatly impaired, albeit normal aggregation restored within 3 hours. Although changes in global clotting times and platelet aggregation were mostly transient, it is possible that CM usage in patients with thrombocytopenia, sickle cell phenomenon, and on anticoagulant-antiplatelet drugs may present a serious risk to their hemostatic integrity.
There is growing interest in low molecular weight heparin for the management of thromboembolic disease in pregnancy. Greater understanding of the risk of thromboembolic disease versus the risk of various management practices is urgently needed to reduce maternal mortality and embryopathy in the fetus.
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