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Biomedical subjects

B Bennett

Publications and source records attributed to B Bennett.

At least 37 records · Page 2Linked to original sources
PubMed1989

The bleeding disorder in acute promyelocytic leukaemia: fibrinolysis due to u-PA rather than defibrination.

Three consecutive patients with acute promyelocytic leukaemia who presented with severe haemorrhagic syndromes were studied and the findings contrasted with those of two patients with classical defibrination after electroshock or complicated labour. The leukaemic patients showed no depletion of fibrinogen. There was no evidence of disordered thrombin generation by either intrinsic or extrinsic pathway sufficient to account for their haemorrhage. All, however, showed strikingly enhanced fibrinolytic activity, which could have accounted for bleeding. This fibrinolytic disorder was characterized by free u-PA in the plasma and differed from that seen after classical defibrination, where free t-PA was observed. U-PA was found also in malignant promyelocytes, which may be the source of u-PA activity in the patients' plasma. Bleeding in promyelocytic leukaemia may be primarily a fibrinolytic disorder.

Electrophoresis, Polyacrylamide Gel↗
PubMed1989

A critical care helicopter system in trauma.

Civilian helicopters and emergency medical services in the United States have been in existence for approximately 15 years. The rapid growth of this type of health care delivery coupled with an increasing number of accidents has prompted professional and lay scrutiny of these programs. Although they have a demonstrated history of benefit to patients, the type and severity of injuries to patients who are eligible for helicopter transportation need further definition. The composition of the medical crews and the benefits that particular crew members bring to the patients require ongoing evaluation. Significant questions regarding the number of pilots in a helicopter and in a program remain to be answered. This article reviews the role of emergency medical air transport services in providing care to trauma patients, staff training and evaluation, and safety criteria and offers recommendations to minimize risks to patients and crews.

Aircraft↗
PubMed1989

Experience with minimal complications in implanted catheters in children.

Eighty-two patients, ranging in age from 11 months to 24 years, underwent the percutaneous placement of an implanted catheter in order to have improved venous access. Thirty-five patients (43%) were beginning chemotherapy for cancer, four (5%) had a chronic hematologic disorder, and the remaining 43 (52%) were on chemotherapy for cancer. The mean duration of catheter function was 168 days (range of 7-1,030 days), with a cumulative experience of 18,812 days of catheter use. Complications were minimal. Only four catheters (5%) required removal secondary to infection, infiltration, or tissue breakdown. Substantially reduced complication rates were observed as compared to other studies using implanted central venous catheters. Implanted central venous catheters were proven to be safe in patients with hematologic disorders. These catheters enhance the ability to infuse chemotherapy, hyperalimentation, blood products, anesthesia, and imaging solutions and are safe to use in patients with a hemostatic or host defense deficiency.

Adolescent↗
PubMed1988

Dermal penetration of avermectin B1a in the rhesus monkey.

Forearms of rhesus monkeys were treated with [3H]avermectin B1a in three different vehicles and concentrations so that the penetration of avermectin B1a through skin could be determined. In order to simulate exposure of farm workers, such as mixer-loaders, applicators, and harvesters, to this pesticide, avermectin B1a was applied to the forearms of the monkeys as an emulsifiable concentrate (300 micrograms/monkey), a diluted emulsifiable concentrate (4.5 micrograms/monkey), and as a suspension in water (216 micrograms/monkey). After 1 or 10 hr of exposure, the treatment area was washed. The levels of radioactivity were determined in the urine, feces, plasma, and wash. On the basis of the amounts of radioactivity excreted in the urine and feces and the levels of radioactivity in the plasma after dermal application compared to those found after intravenous administration of the compound, less than 1% of the doses was absorbed. These data indicate that avermectin B1a would not readily penetrate the skin of farm workers exposed to it. Therefore, the hazard to farm workers exposed to this compound would be substantially mitigated.

Animals↗
PubMed1988

A plasminogen activator inhibitor (PAI-2) circulates in two molecular forms during pregnancy.

During normal pregnancy maternal haemostasis alters to protect against bleeding with a rise in plasma clotting factor levels and increased inhibition of fibrinolysis. The latter is due in part to increased levels of the 48 kDa plasminogen activator inhibitor (PAI-1) present in the plasma of non-pregnant individuals. A second plasminogen activator inhibitor (PAI-2) occurs in placenta and in a cultured histiocytic lymphoma cell line. We report here the identification by SDS-PAGE and zymography of PAI-2 in plasma during normal pregnancy. PAI-2 was present in two molecular forms of about 75 and 130 kDa, which were detectable at 12 weeks gestation and which persisted in the maternal circulation for up to 7 days after delivery. These forms of PAI-2 appear to be distinct from purified PAI-2, which has a molecular mass of 47-60 kDa and which is not normally detectable in this zymographic system, since it is sensitive to denaturants. The novel forms of PAI-2 may represent complexes or aggregates that retain activity after SDS-PAGE.

Female↗
PubMed1988

Accelerated increase in aortic diameter in patients treated for lymphoma.

Cytotoxic chemotherapeutic agents, particularly the anthracyclines, are known to be cardiotoxic, but toxic effects on the aorta have not previously been documented. In this study, diameters of ascending and descending thoracic aortae were measured by computerized tomography in 69 patients with lymphoma, before and after first-line treatment with one of 7 different regimes. Minor increases in aortic diameter over the study period due to the aging process were expected. These increases were greater than anticipated in both the ascending and the descending aortae after chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and CVP (cyclophosphamide, vincristine, and prednisolone) regimes. Smaller changes, or changes which were not statistically significant, were noted after MVPP (mustine, vinblastine, procarbazine, and prednisolone), ChlVPP (chlorambucil, vinblastine, procarbazine, and prednisolone), ChlVP (chlorambucil, vincristine and prednisolone), mediastinal radiotherapy, and radiotherapy plus MVPP (MVPP/XRT). Cardiovascular damage associated with certain forms of cytotoxic therapy is not confined to the heart, but also affects the aorta.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

The effects of four drug regimens on sister chromatid exchange frequency in patients with lymphomas.

Patients undergoing first-line chemotherapy after diagnosis of lymphoma have considerable DNA damage in their peripheral blood lymphocytes, using sister chromatid exchange (SCE) frequency as a sensitive indicator. Different drug regimens produce different patterns of changes in SCE frequency. These may be related to their potential to induce second malignancies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Condylomata acuminata of the urinary bladder. Natural history, viral typing, and DNA content.

Three patients with condylomata acuminata of the urinary bladder are reported. Two of the patients were immunosuppressed, and one had longstanding extensive condylomata acuminata of the external genitalia and adjacent areas. All lesions recurred at least once and were difficult to treat. The diagnosis was confirmed by in situ hybridization on archival material with human papillomavirus (HPV) DNA probes under stringent conditions. In two of the patients, probes for HPV types 6 and 11 were positive; HPV 11 only was identified in one patient. Probes for HPV types 16 and 18 and pBR322 vector controls were negative. In one patient with a strong hybridization signal, the lesion was also positive for common papillomavirus antigen. DNA content measured by cytophotometry of Feulgen-stained whole nuclei isolated from lesions in two patients revealed a markedly aneuploid DNA pattern. Whether this is a factor in the behavior of the lesions is not known at this time. Although rare, HPV infection of the urinary bladder may result in widespread condylomatosis and may mimic giant condylomas of Buschke-Löwenstein or even verrucous carcinomas, sometimes necessitating radical treatment. Nevertheless, until there is proof to the contrary, the lesions must be considered benign and should not be confused with squamous cancer of the bladder.

Adult↗
PubMed1988

Plasminogen activator inhibitor (PAI-1) in plasma and platelets.

The distribution of PAI-1 in the plasma and platelets of normal individuals and of patients with platelet abnormalities was studied. An ELISA, capable of measuring PAI-1 in plasma at 1.5 ng/ml, and a functional assay of t-PA inhibition were used to assay platelet-free plasma (PFP), platelet-rich plasma in which the platelets were lysed (PRP) and serum. The PAI-1 concentration of normal PFP was 21.0 +/- 7.2 ng/ml (mean +/- SD) and those of PRP and serum were 282.6 +/- 68.0 and 270.3 +/- 71.9 ng/ml. The concentration of PAI-1 in PRP was proportional to the platelet count with 0.67 +/- 0.18 ng/10(6) platelets. Patients with thrombocytopenia had approximately normal PAI-1 concentrations in PFP; the extremely low concentrations in serum or PRP reflected the platelet count. A patient with grey platelet syndrome showed a comparable pattern, confirming that PAI-1 occurs in the platelet alpha-granules and indicating that the plasma concentration of PAI-1 is independent of the platelet pool of PAI-1. The median inhibitory activities towards t-PA were 1.6, 8.7 and 8.3 units/ml in normal PFP, PRP and serum respectively. PAI-1 in PFP had a median specific activity (units/mg PAI-1) about 5-fold higher than platelet PAI-1. Plasma and platelets represent two distinct pools of PAI-1, both of which should be considered in studies on the relationship between circulating PAI-1 and thrombotic disease.

Adult↗
PubMed1987

Plasminogen activator inhibitor from human endothelial cells. Purification and partial characterization.

An inhibitor of plasminogen activator was purified to apparent homogeneity from human umbilical vein endothelial cell conditioned medium. The purification was achieved by a speedy and simple two-step procedure, without the use of denaturants. The purified protein was a single-chain glycoprotein with apparent molecular mass of 48 kDa. The purified inhibitor had a specific activity of 8500 U/mg protein and the activity could be stimulated about fourteenfold by treatment with denaturants. An antiserum to the purified inhibitor was raised in rabbits. It recognised plasminogen activator inhibitor from platelets and plasma as well as from cultured endothelial cells. The immunoglobulin fraction of the antiserum neutralised the functional activity of the inhibitor from all these sources.

Animals↗
PubMed1987

Regulation and role of guanylate cyclase-cyclic GMP in vascular relaxation.

Three classes of vasodilators mediate their effects through the activation of guanylate cyclase and the increased synthesis of cyclic GMP. Nitrovasodilators such as nitroglycerin, nitroprusside, hydroxylamine, azide, etc. result in the generation of the nitric oxide free radical that activates the cytosolic (soluble) isoenzyme form of guanylate cyclase. These agents have been useful in increasing cyclic GMP synthesis in numerous model systems and these effects are independent of extracellular calcium. The increased synthesis of cyclic GMP and the activation of cyclic GMP-dependent protein kinase result in the altered phosphorylation of many smooth muscle proteins including the dephosphorylation of myosin light chain, which is associated with vascular and tracheal smooth muscle relaxation. These latter effects may result from cyclic GMP decreasing cytosolic free calcium concentrations and the activity of myosin light chain kinase. Another class of vasodilators, designated endothelium-dependent vasodilators, includes a long list of agents such acetylcholine, histamine, A23187, ATP, thrombin, etc. that relax vessels only when the endothelium is intact. These agents result in the increased endothelial synthesis and/or release of a factor(s) designated endothelial-derived relaxant factor (EDRF), the structure of which is unknown. This labile factor also activates the soluble isoenzyme form of guanylate cyclase in the smooth muscle resulting in cyclic GMP accumulation and the same cascade of events as above. There is evidence that even under basal, non-stimulated conditions there is EDRF release that influences vascular tone due to the increased synthesis of cyclic GMP. A third class of vasodilators, atrial natriuretic factor (ANF) or atriopeptins, includes a family of peptides that are produced in cardiac atria and other tissues and influence cardiovascular volume and dynamics by causing natriuresis, diuresis, vasodilation and decreased renin, aldosterone and vasopressin secretion. These peptide hormones also increase cyclic GMP synthesis in vascular, renal, adrenal and other tissues. These effects are mediated through specific ANF receptors that couple to and activate the membrane (particulate) isoenzyme form of guanylate cyclase and increase cyclic GMP-dependent protein kinase activity. There are two ANF receptor subtypes in most cells and tissues that are 130,000 and 66,000 daltons. The ANF receptor of about 130,000 daltons, designated receptor ANF-R1 copurifies with particulate guanylate cyclase through numerous procedures and may be part of the membrane-associated guanylate cyclase complex.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Plasminogen activator in normal subjects after exercise and venous occlusion: t-PA circulates as complexes with C1-inhibitor and PAI-1.

Exercise to exhaustion was associated with the appearance in plasma of plasminogen activator (PA) in several mol wt forms, as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with zymography. A number of active bands, all immunologically identified as tissue-type PA (t-PA), were observed. The major form had an apparent mol wt of approximately 60,000 and is due to free t-PA. The other strong bands had apparent mol wts of approximately 110,000 and 180,000. The 110,000 band, also present in pre-exercise samples, represents t-PA complexed with its major inhibitor (PAI-1), and the 180,000 band is due to t-PA complexed with C1 inhibitor. The released forms of t-PA were cleared rapidly after cessation of exercise at exhaustion. Urokinase-type PA (u-PA) activity was also identified in pre- and postexercise samples at an apparent mol wt of approximately 50,000. This is consistent with its being free u-PA; no complexed forms of u-PA were observed. Qualitatively similar changes in plasma PA were observed after venous occlusion. Small quantities of plasmin were generated after strenuous exercise, as observed by detection of plasmin-alpha 2-antiplasmin complex by two-dimensional immunoelectrophoresis in three of five subjects. This complex was cleared rapidly after cessation of exercise. Plasmin-alpha 2-antiplasmin complex was not detected in any of the subjects after venous occlusion.

Fibrinolysin↗
PubMed1986

Haemoglobin concentration and linear cardiac output, peripheral resistance, and oxygen transport.

Increasing the haemoglobin concentration results in increased oxygen transport at the cost of increased blood viscosity. This suggested the concept of an optimum packed cell volume for maximising oxygen transport and a study was therefore conducted seeking supportive evidence. Linear cardiac output was measured as minute distance by Doppler ultrasound in 40 patients with haemopoietic disorders who had stable haemoglobin concentrations ranging from 30 to 200 g/l. The correlation between haemoglobin concentration and minute distance (r = -0.45; p less than 0.01) was negative, and correlations between haemoglobin concentration and mean blood pressure (r = 0.66; p less than 0.001) and haemoglobin concentration and peripheral resistance (r = 0.64; p less than 0.001) were positive. Calculated oxygen transport increased across the whole range of haemoglobin values. These results suggest that adjustment of peripheral resistance in response to oxygen availability overrides the influence of blood viscosity on cardiac output and that the optimum packed cell volume for oxygen transport is the highest that can be achieved.

Biological Transport↗