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Biomedical subjects

M E Carr

Publications and source records attributed to M E Carr.

At least 91 records · Page 5Linked to original sources

Beta blockade by oral propranolol and labetalol.

beta-Adrenergic blockade after single, oral doses of labetalol or propranolol was evaluated in a double-blind, placebo-controlled study by an isoproterenol sensitivity test and handgrip exercise in 10 healthy men. The tests were performed with subjects resting in a supine position. At the doses used, there was no effect on heart rate and blood pressure in either the resting position or in the isometric exercise phase. It is possible that exercise-induced changes in blood pressure and heart rate were reduced by higher vagal tone in this young group tested in the supine position. Isoproterenol increased heart rate and reduced diastolic blood pressure in a dose-dependent manner. The dose of isoproterenol at which heart rate increased 25 bpm above the resting rate (CD25; 1.36 +/- 0.18 microgram) was of the order of that at which diastolic blood pressure fell 25 mm Hg from baseline (HD25; 1.07 +/- 0.07 microgram). There was a significant positive correlation between CD25 and HD25 in the 10 subjects. Propranolol and labetalol induced a dose-dependent, parallel shift to the right in the dose-response curves of isoproterenol effects on heart rate and diastolic blood pressure, indicating that both drugs are nonselective, competitive antagonists of beta-adrenergic receptors. On the average, propranolol was 17 and 19 times more potent than labetalol in antagonizing the chronotropic and hypotensive actions of isoproterenol, respectively.

Administration, Oral↗

Electroconvulsive therapy in a patient with unsuspected pheochromocytoma.

We have described a patient given electroconvulsive therapy who was subsequently found to have a pheochromocytoma. The variability of the manifestations of pheochromocytoma combined with the nature of complaints normally encountered in the psychiatric population makes the diagnosis of pheochromocytoma difficult in such patients. Pheochromocytoma remains, however, an absolute contraindication for ECT and should therefore be ruled out if the patient is hypertensive or has episodic symptoms.

Adrenal Gland Neoplasms↗

Molecular analysis of multiple-resistance plasmids transferred from gram-negative bacteria isolated in a urological unit.

Forty-one isolates of multiply resistant gram-negative bacteria causing infection in a urological unit of a Dublin hospital were collected during a 6-month period. Twenty-one isolates transferred multiple resistance to an Escherichia coli K-12 recipient in liquid matings. Serratia marcescens, Proteus morganii, Proteus vulgaris, and E. coli isolates harbored similar 120-megadalton IncC plasmids, whereas Enterobacter cloacae strains transferred a 160-megadalton plasmid of a different Inc group. Southern hybridization experiments were performed with purified fragments cloned from one IncC plasmid as probes. They were hybridized to plasmid sequences in total cellular DNA extracts, showing that the IncC plasmids were very closely related. This suggests that the same plasmid has transferred to different bacterial species in the hospital environment.

Bacteriuria↗

Simultaneous outbreaks of infection due to Serratia marcescens in a general hospital.

Seventy isolates of Serratia marcescens were obtained from 30 patients in different units of one hospital between April 1982 and February 1983. No common source was found. Not all isolates were multi-resistant and nearly all that were, fell into two main groups, A and B. These groups were defined by phage typing and cephalosporin sensitivity, all apart from one Group B isolate were multi-resistant, whereas Group A isolates contained multi-resistant and sensitive strains. Plasmid screening, resistance transfer studies and plasmid elimination experiments demonstrated that the multi-resistant phenotype was due to a 120 Mdal transmissible plasmid. Resistance to cephalosporins was chromosomally encoded.

Anti-Bacterial Agents↗

Bacteraemia during prostatectomy and other transurethral operations: influence of timing of antibiotic administration.

The relation between the timing of prophylactic antibiotic administration and the occurrence of bacteraemia during transurethral operations was studied in 112 patients whose urine was infected before operation. Blood cultures taken during operation were positive in 15 (60%) of 25 patients who did not receive appropriate antibiotics, in 13 (21%) of 63 patients who were given appropriate antibiotics less than 24 h before operation, and in none of 24 patients in whom antibiotic "cover" was started more than 24 h before operation. In all cases the bacteraemia was transient. No patient developed septicaemia. The implications of these findings for the optimum timing of antibiotic administration to patients with preoperative bacteriuria are discussed.

Anti-Bacterial Agents↗

Hereditary dysfibrinogenemia in a patient with thrombotic disease.

A new case of congenital dysfibrinogenemia, in which the patient has severe thrombotic disease, is reported. The abnormal fibrinogen molecules are characterized by normal fibrinopeptide release with thrombin and defective polymerization in the formation of fibrin. Clotting times with ancrod and reptilase are significantly prolonged. All other coagulation tests (except those for fibrinogen function) are normal, and the patient has no other underlying disease. The apparent paradox of defective fibrinogen, which clots abnormally and is yet associated with thrombotic disease, can be explained by further analysis of the patient's fibrinogen. The two important functional properties of this fibrinogen are: (1) it forms fibrin gels that are extremely rigid, and (2) the fibrin is highly resistant to lysis by plasmin. Thus, although the abnormal fibrinogen forms defective clots, the fibrin that is formed cannot be removed by the fibrinolytic system. These results provide a molecular explanation for the thrombotic disease in this patient. This abnormal fibrinogen appears to have unique characteristics and has been designated as fibrinogen Chapel Hill Ill.

Adolescent↗

Permeability of hyaluronic acid solutions. The effects of matrix concentration, calcium, and pH.

The permeability of hyaluronic acid solutions was measured in a chamber closed at each end of semi-permeable membranes. Permeability was strongly concentration dependent below 1.0 gm% hyaluronic acid. Small changes in the ionic environment of 1.0 gm% hyaluronic acid solutions also altered permeability. The permeability of such solutions decreased by a factor of 4.7 in the presence of as little as 5 mM calcium ion and showed optimum permeability at pH 7.0. The pH optimum was not noted in hyaluronic acid preparations known to contain only small amounts of protein.

Calcium↗

The effect of dextran 70 on the structure of plasma-derived fibrin gels.

Measurements of fiber mass-length ratios and fibrin gel elastic modulus as a function of dextran 70 concentration are reported for fibrin gels derived from human plasma. Dextran 70 at 0.1 mg/ml produces a 50% reduction in the storage modulus of fibrin gels obtained from human plasma diluted 1:10 with saline. Since the fibrin fiber diameter increases as only a weak function of the dextran 70 concentration, the lower elastic modulus most likely results from a reduction in network branch points. Aprotinin is also shown to modulate the dextran effect.

Aprotinin↗

Detection of an abnormal plasma clot structure by a simple rigidity assay.

We report here on a patient whose abnormal fibrin clot was detected via the measurement of clot rigidity with a simple buoyant inner cylinder elastometer. The patient's clinical coagulation studies were all within normal limits except for prolonged thrombin and reptilase clotting times and high level of fibrin split products. The measured rigidity of the patient's clot was approximately ten times lower than that of a clot formed from normal pooled plasma. Light scattering studies indicated that this modified structure was not caused by a gross change in gel fiber morphology. Antithrombin activity was eliminated as a possible cause of the altered clot structure; this suggests the possibility of a modified fibrinogen. Abnormalities in the reptilase time and fibrinogen levels in two siblings support the hypothesis that the modification is an inherited defect. We suggest that the simple measurement of rigidity can be used rountinely to detect abnormalities in plasma clot structure. The screening for such disorders should be of importance to clinician, patient, and biochemical researcher.

Aged↗

The clinical features of infantile gastroenteritis due to rotavirus.

The symptoms of 100 hospitalised cases of rotavirus infantile gastroenteritis are described. Most patients presented with high fever between the 2nd and 5th day, having started with diarrhoea or vomiting or both. 42% of the infants had upper respiratory tract symptoms. Severe electrolyte disturbance did not occur, although there was a suggestion of a correlation between the higher blood ureas and the number of rotavirus particles in the stools. The mean duration of illness of uncomplicated cases was 13.4 days. Infants were more severely affected when enteropathic coliforms were also present, the total duration of illness being extended to 23 days. It is suggested that rotavirus or similar virus infection may be an essential precursor in the majority of coliform gastroenteritis.

Acute Disease↗

Disseminated intravascular coagulation: pathogenesis, diagnosis, and therapy.

Disseminated intravascular coagulation (DIC), resulting in an acute bleeding diathesis, is always a secondary complication of an underlying disease. Coagulation triggered by the primary process causes consumption of clotting factors and platelets, and ischemic damage secondary to fibrin deposition. Concurrent activation of the fibrinolytic system results in additional clotting factor consumption and the production of fibrin-degradation products (FDP). The combination of decreased clotting factors, FDP, and thrombocytopenia may ultimately culminate in a bleeding diathesis. The balance between the thrombotic and hemorrhagic processes results in a constellation of signs and symptoms. Diagnosis depends on an awareness of predisposing pathologic states and the application of appropriate laboratory tests. Therapy consists of treating the underlying disease and temporizing with an appropriate replacement therapy. Heparin infusion may be of benefit under certain circumstances. The pathogenesis, diagnosis, and treatment of DIC, including new laboratory tests and experimental therapy, are reviewed.

Disseminated Intravascular Coagulation↗

Rewarming by hemodialysis for hypothermia: failure of heparin to prevent DIC.

Disseminated intravascular coagulation (DIC) is an infrequent but known complication of hypothermic injury. Previous work with a dog model had indicated that DIC could be prevented if the animals were treated with heparin prior to rewarming. We report here the case of a young man treated with core rewarming by hemodialysis who developed DIC despite the use of heparin during dialysis.

Adult↗

Diabetes mellitus: a hypercoagulable state.

Eighty percent of patients with diabetes mellitus die a thrombotic death. Seventy-five percent of these deaths is due to cardiovascular complications, and the remainder is due to cerebrovascular events and peripheral vascular complications. Vascular endothelium, the primary defense against thrombosis, is abnormal in diabetes. Endothelial abnormalities undoubtedly play a role in the enhanced activation of platelets and clotting factors seen in diabetes. Coagulation activation markers, such as prothrombin activation fragment 1+2 and thrombin-anti-thrombin complexes, are elevated in diabetes. The plasma levels of many clotting factors including fibrinogen, factor VII, factor VIII, factor XI, factor XII, kallikrein, and von Willebrand factor are elevated in diabetes. Conversely, the level of the anticoagulant protein C (PC) is decreased. The fibrinolytic system, the primary means of removing clots, is relatively inhibited in diabetes due to abnormal clot structures that are more resistant to degradation and an increase in plasminogen activator inhibitor type 1 (PAI-1). Increased circulating platelet aggregates, increased platelet aggregation in response to platelet agonists, increased platelet contractile force (PCF), and the presence of higher plasma levels of platelet release products, such as beta-thromboglobulin, platelet factor 4, and thromboxane B(2), demonstrate platelet hyperactivity in diabetes. This constellation of findings supports the clinical observation that diabetes is a hypercoagulable state. This article briefly reviews the published evidence for this conclusion and the putative roles played by hyperglycemia and hyperinsulinemia in its development.

Anticoagulants↗

Size and density of fibrin fibers from turbidity.

In agreement with earlier observations that the angular dependence of light scattering by fibrin gels obeys the theory for light scattering by very long and thin rigid rodlike particles (intensity proportional to the square of half the scattering angle), we find that the turbidity, tau, of the less opaque gels varies as the inverse third power of the wavelength, lambda. Mass-length ratios of the fibers calculated from these two measurements closely agree. For fibrin gels containing fibers with a very high mass-length ratio (of which we had not been able to obtain interpretable scattering data), the turbidity is found not quite to vary as 1/lambda3. For these opaque gels, the fiber diameter is no longer negligible with respect to the wavelength. It is shown how the radius of gyration of the fiber cross section (and therefore the radius of cylindrical fibers) can be obtained from the ratio of slope and intercept of a plot of 1/tau lambda3 vs. 1/lambra2. The square of the radius of the fibers is found to be proportional to the mass-length ratio. The density of the fibers is calculated to be 0.28. This corresponds to a ratio of fiber volume to volume of protein contained in the fiber of 5.0.

Fibrin↗

Protein S and C4b-binding protein levels in patients with stroke: implications for protein S regulation.

Protein S circulates either free or bound to C4b-binding protein (C4b-BP). Only free protein S possesses cofactor activity for protein C, a physiologic anticoagulant. Deficiencies of either protein C or protein S are associated with increased thrombotic risk. Over a 23-month period, 40 patients with low free protein S were identified. Eight of these patients were found to have suffered a stroke. This study examined the relationship between total S, free S, and C4b-BP in 15 healthy adult volunteers, in 20 patients with normal protein S levels, in 40 patients with decreased free protein S levels, and in 8 patients with combined low free S levels and stroke. Total and free protein S and C4b-BP levels were determined using the method of Laurell. In healthy adults, free protein S increased with increasing total protein S (r = 0.60). In patients with normal free S, the total S level increased as C4b-BP increased (r = 0.74), and the free S level remained constant. In patients with low free S, total S did not increase with increasing C4b-BP. In stroke patients, the correlation between free S and total S was actually negative (r = -0.449). Evaluation of dissociation constants for the protein S-C4b-BP complex revealed enhanced binding in patients with low levels of free protein S. A non-C4b-BP protein S binding protein, a previously undescribed regulatory factor which modulates S binding to C4b-BP, or shifts in the amount of non-protein S binding C4b-BP are possible explanations of these results.

Adult↗