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Biomedical subjects

B Bennett

Publications and source records attributed to B Bennett.

At least 91 records · Page 5Linked to original sources

Transferrin in disease II: defects in the regulation of transferrin saturation with iron contribute to susceptibility to infection.

Patients with leukemia were found to have a high percentage of saturation of their serum transferrin with iron to an extent only rarely observed with other malignancies. This was associated with a reduced ability of their serum to inhibit the growth of a test strain of Pseudomonas aeruginosa. Serum iron, transferrin, and related parameters were measured serially in patients undergoing bone marrow transplantation for leukemia or aplastic anemia. It was found that a high proportion of these patients also have a high saturation of their transferrin with iron. This was related to three distinct physiologic deficits: a low level of serum transferrin; a high level of iron; and an inability to reduce the level of serum iron during infection. Three of six patients who were unable to reduce their serum during fever and infection subsequently died of sepsis. These data support the hypothesis that derangements in nonspecific serologic defense mechanisms involving iron contribute to susceptibility to infection in patients with leukemia undergoing bone marrow transplantation.

Adolescent

Plasmin-alpha 2-antiplasmin complexes in bleeding disorders characterized by primary or secondary fibrinolysis.

A two-dimensional immunoelectrophoresis (2DIEP) method detects plasmin complexed to its major inhibitor, alpha 2-antiplasmin, in plasma in the blood of patients during (a) thrombolytic therapy with urokinase, (b) episodes of disseminated intravascular coagulation (DIC) with active fibrinolysis, and (c) episodes of fibrinolytic haemorrhage without evidence of DIC. Clearance of the complexes from the blood is rapid and their detection thus implies active plasmin generation at the time of blood sampling or within the preceding 24 h. Abolition of the complexes using tranexamic acid therapy allowed surgery without bleeding in two previously grossly haemorrhagic patients in group (c). Antithrombin III complexed with activated procoagulants was detected using a similar 2DIEP method in only two of four patients with DIC. Abnormalities of alpha 2-macroglobulin were detected on 2DIEP of plasma in the patients studied with proteolytic disorders; these did not appear to reflect complex formation.

Abruptio Placentae

Prophylactic antithrombotic therapy with stanozolol in patients with familial antithrombin III deficiency.

Three patients with familial antithrombin III deficiency underwent a trial of prophylactic antithrombotic therapy with stanozolol. An increase in plasma fibrinolytic activity and antithrombin III was seen. Acute venous thrombosis occurred in two patients; in the first patient thrombosis was precipitated by venography but in the second no precipitating factor was found. Our experience suggests that stanozolol is not a suitable prophylactic agent in patients with familial antithrombin III deficiency.

Antithrombin III

Measurement of platelet life-span in normal subjects and patients with myeloproliferative disease with indium oxine labelled platelets.

The use of 111Indium oxine as a platelet label for the performance of platelet life-span studies has been examined. Platelet life-span in normal subjects varied between 8 X 10 and 10 X 36 d. Patients with primary thrombocythaemia had clearly reduced platelet life-span whether or not they presented with vascular occlusion and this abnormality persisted after reduction of the platelet count to normal by busulphan therapy. Patients with similarly elevate platelet counts due to chronic granulocytic leukaemia or after splenectomy had platelet life-span values in the normal range. Plasma beta-TG levels could not be used to predict platelet life-span in these groups of patients. Measurement of platelet life-span using 111Indium labelled platelets is a useful technique in the examination of platelet function in occlusive vascular disease.

Adult

Haemorrhage associated with large abdominal aortic aneurysms.

Two patients are described who each had a major haemorrhage after minor surgery and who additionally had large abdominal aortic aneurysms. Neither had depletion of platelets or coagulation factors sufficient to account for bleeding. Both had grossly enhanced fibrinolytic activity with evidence of plasmin generation in the circulation. In one patient insertion of an aortic graft was rapidly followed by resolution of the fibrinolytic abnormalities. Overactive fibrinolysis, rather than coagulation factor consumption may account for some of the bleeding syndromes complicating abdominal aortic aneurysms.

Aged

Plasminogen activators in alcoholic cirrhosis: demonstration of increased tissue type and urokinase type activator.

Plasma samples from patients with alcoholic cirrhosis were analysed for plasminogen activators and for inhibitors of the fibrinolytic system. Plasminogen activator activity was considerably increased in patients' plasma compared with normal. Immunochemical characterisation of these plasminogen activators showed that they included both tissue type and urokinase type plasminogen activator. The major inhibitor of plasmin, alpha 2-antiplasmin, was decreased in the patients, but no evidence for the generation of plasmin was found.

Electrophoresis, Polyacrylamide Gel

Standardized automated assay for functional alpha 1-antitrypsin.

We describe an enzymic assay for the functional activity of alpha 1-antitrypsin, in which tosyl-Gly-Pro-Lys-p-nitroanilide acetate (Chromozym PL) is the trypsin substrate. For the indicating reaction, the concentration of substrate is about double the Km of its reaction with trypsin. This assay is an improvement over reactions involving N-alpha-benzoyl-DL-arginine p-nitroanilide as substrate, the solubility of which in water is less than the Km of its reaction with trypsin. The assay is standardized in terms of active sites of trypsin inhibited per liter of serum, with p-nitrophenyl-p'-guanidinobenzoate as the active site titrant. The results agreed well with those by an immunonephelometric assay for alpha 1-antitrypsin (r = 0.953). The within-run and run-to-run precision was approximately 3%. The results of the assay varied linearly with alpha 1-antitrypsin concentration from 0 to 60 mumol/L of serum. The minimum sample size was 50 microL, and analysis of 24 samples took less than 20 min.

Aniline Compounds

The value of autologous indium (111In)-labelled platelets in the diagnosis of renal transplant rejection.

Serial pelvic imaging after injection of autologous platelets labelled with 111In was used to study 22 consecutive patients following cadaver renal transplantation. Increases in isotope uptake by the allografts were observed during episodes of acute rejection (12/22) but not during acute tubular necrosis (4/22). The technique was not influenced by oliguria or hemodialysis therapy. Extra-renal accumulations of labelled platelets were noted in perinephric hematomata and deep vein thromboses.

Acute Kidney Injury

The adjuvant activity of nonionic block polymer surfactants. II. Antibody formation and inflammation related to the structure of triblock and octablock copolymers.

We tested the ability of 17 surface-active agents to enhance antibody formation and inflammation. The surfactants were all block copolymers of hydrophilic polyoxyethylene (POE) and hydrophobic polyoxypropylene (POP), which differed in m.w. and mode of linkage of POP to POE. Mice were injected in each rear footpad with 1.25 mg of each surfactant with 25 micrograms of bovine serum albumin in an oil-in-water emulsion. Each agent produced a distinct pattern of immune response and inflammation. Preparations that are large and insoluble with the POE chains flanking the POP chains were very effective adjuvants for increasing antibody formation. They also activated complement and induced the release of chemotactic factors from serum. Increasing the percent of POE decreased adjuvant activity and inflammation. Decreasing the m.w. of the molecules while maintaining the proportions of POP and POE decreased the adjuvant activity and increased inflammation. Preparations synthesized in the reverse order, with the POP flanking POE, tended to induce granulomas instead of antibody. These data demonstrate that block copolymer surfactants have a spectrum of biologic activities that depend on the size and arrangement of their constituent parts. We suggest that much of the activity of these agents derives from their ability to form adsorptive surfaces similar to those of a mycobacterial glycolipid, quartz, and monosodium urate.

Adjuvants, Immunologic

Endotracheal intubation in the prehospital phase of emergency medical care.

One hundred seventy-eight endotracheal intubations by paramedics were reviewed prospectively during a nine-month period; 149 patients (83.7%) had medical conditions, and 29 (16.2%) had trauma. The endotracheal tube was successfully placed in 172 (96.6%); in four patients (2.2%), attempts were unsuccessful, and in two patients (1.1%), the attempt was aborted. There were no incidences of reported complications. We conclude that endotracheal intubation can be accomplished successfully outside the hospital by paramedical personnel. Comprehensive training and continuous medical control of paramedics' activities seem to be essential requirements for its success.

Adolescent

Cis-platin based combination chemotherapy for advanced ovarian cancer. High overall response rate with curative potential only in women with small tumor burdens.

Thirty-eight women with advanced ovarian cancer were given monthly cycles of intravenous cyclophosphamide, Adriamycin (doxorubicin) and cis-platin, and oral hexamethylmelamine. Of 26 with tumor which would be evaluated for response, 42% had complete remission and 50% partial remission. Median time to disease progression from entry for all 38 patients was 13 months, and median survival 23.5 months. The bulk of tumor at the time chemotherapy was begun was the only significant prognostic factor for time to disease progression and survival. Of the seven women surviving free of disease a median of three years later, five had no mass greater than 2 centimeters in diameter at entry. Toxicity was predominantly myelosuppression and vomiting, with mild peripheral neuropathy in 27% and no significant renal or cardiac toxicity. The response rate of 92% is much higher than that previously reported with melphalan, and the survival considerably longer. The toxicity is acceptable, given the substantial improvement in results.

Adult

Splenectomy and infection in Hodgkin's disease.

The incidence of infection in 56 patients with Hodgkin's disease who had undergone staging laparotomy with splenectomy was compared with that of 28 non-splenectomized patients with Hodgkin's disease treated concurrently. The results suggest that splenectomy does not result in a major change in the incidence of infection experienced by such patients with stage II or stage III disease. Aggressive therapy may be of greater importance in increasing the susceptibility to infection in Hodgkin's disease.

Adolescent

Preoperative antithrombin III activities and lipoprotein concentrations as predictors of venous thrombosis in patients with fracture of neck of femur.

The presence or absence of venous thrombosis was determined by the technique of autologous 111indium-labelled platelets in 64 patients following reduction and fixation of fractures of the neck of femur. Venous thrombosis was found in 41 (64%) of these patients. Compared to the thrombosis-negative group, the thrombosis-positive group had a significantly lower mean serum antithrombin, and higher mean antithrombin consumption during clotting in the immediate preoperative period. No significant differences were seen between the two groups in plasma ATIII activities, fibrinogen, alpha-2-macroglobulin, serum lipoproteins or age. Significant correlations were seen between ATIII activities and lipoprotein fractions; these are discussed.

Adult

Frequency of venous thrombosis in patients with an exacerbation of chronic obstructive lung disease.

The presence or absence of venous thrombosis was determined in 29 patients with an acute exacerbation of chronic obstructive lung disease by the technique of autologous platelet labelling with indium-111. Deep venous thrombosis was diagnosed in 13 patients and in nine of these patients thrombosis was located proximal to the knee--that is, in areas associated with an appreciable risk of pulmonary embolism. One patient died; pulmonary emboli were found at postmortem examination. The incidence of venous thrombosis seen in this study is high enough to suggest that these patients may benefit from prophylactic antithrombotic treatment.

Aged

A new life-long hemorrhagic disorder due to excess plasminogen activator.

A life-long bleeding disorder is described, characterized by hemorrhage occurring after surgery, injury, or dental extraction, and finally by spontaneous intracerebral bleeding. No abnormality of platelet function or plasma coagulation was demonstrable, but grossly enhanced overall fibrinolytic activity was present. The patient had, additionally, a hyperlipidemia with gross arterial atheroma and a family history of myocardial infarction but not of any hemorrhagic disorder. Laboratory studies led to the conclusion that the enhanced fibrinolysis was due to consistently greatly raised levels of a plasma plasminogen activator physically and immunologically related to that in human tissues and blood vessel endothelium. No deficiency of any known inhibitor of fibrinolysis was detected. Free plasmin was not detectable in functional assays but continuous intravascular plasmin generation clearly occurred as evidenced by presence of plasmin-alpha 2-antiplasmin complexes and of fibrin/fibrinogen-related antigens. Excessive production of plasminogen activator appeared to have occurred throughout life and to be independent of the hyperlipidemia. The pathologically increased fibrinolytic activity may have accounted for the complete absence of detectable thrombotic vascular occlusion at autopsy despite extensive arterial disease with severe narrowing of coronary and cerebral arteries.

Blood Coagulation Tests

Lipoprotein fractions and antithrombin III consumption during clotting.

Plasma and serum antithrombin levels were measured in functional (initial rate measurement) and immunological assays together with serum lipid levels in normal subjects and patients with coronary artery disease. Specific antithrombin activity in plasma showed a negative correlation with triglyceride levels. The consumption of antithrombin activity during blood clotting was negatively correlated with both serum total triglyceride and heparin precipitable lipoprotein and positively correlated with serum high density lipoprotein cholesterol. Different blood lipoprotein fractions may influence the activity of the antithrombin III molecule.

Adult