How to move patients the easy way--and save your back.
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Biomedical subjects
Publications and source records attributed to B Bennett.
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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)
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.
We have observed an electrophoretically abnormal, nonfunctional species of alpha 1-antitrypsin in serum from patients who were receiving bone-marrow transplants for treatment of leukemia or aplastic anemia. Three of four patients in whose serum this protein appeared died soon after; the fourth recovered, and the disappearance of the abnormal alpha 1-antitrypsin paralleled his recovery. This suggests that the inability to maintain functional activity of alpha 1-antitrypsin predisposes patients to life-threatening complications during recovery from bone-marrow transplants.
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.
We reviewed the medical records of 65 boys with surgically and pathologically proved monorchism. A striking laterality to the left side was identified. In 83 per cent of the patients wolffian structures were present and in 20 per cent microscopic evidence of a terminal nubbin of hyalinized, calcified or hemosiderin-containing tissue was noted. These findings strongly suggest that in most instances of monorchism a testis had been present and had undergone subsequent in utero degeneration. Characterization of the hormonal changes associated with unilateral absent testes was done by determining fasting morning levels of luteinizing hormone and follicle-stimulating hormone. In a subgroup of monorchid boys and age-matched prepubertal unilateral cryptorchid boys luteinizing hormone release factor stimulation also was performed to determine if endocrine analysis could predict the absence of 1 testis.
We evaluated the molecular and physicochemical properties of surfaces formed by defined layers of block copolymers which were especially effective as adjuvants or in the induction of granulomas. The copolymers which were adjuvants formed hydrophilic surfaces with a large area. They bound protein in a way which left it particularly accessible to antibody and induced the activation of complement. Copolymers which induced granulomas, in contrast, formed hydrophobic crystalline surfaces. They bound less protein and did not activate complement, but were toxic for macrophages. Their surfaces were found to be similar to those of the mycobacterial glycolipid trehalose-6,6'-dimycolate or quartz, in that they consisted of regular geometric arrays of hydrophilic and hydrophobic adsorptive domains. These studies demonstrated that changes in the size and arrangement of hydrophilic and hydrophobic blocks in copolymers produce a diversity of surface physicochemical properties which correlate with biologic activity.
We investigated the mechanisms of injury involved in unilateral testis torsion as well as the interventional effects of orchiectomy at 48 h and immunosuppression with corticosteroids in rats. Torsion was associated with abnormal contralateral testis histology and raised antilymphocytes and antisperm antibody titers. Both orchiectomy and steroid administration lessened these findings, suggesting that an immunological process underlies the abnormality seen in this experiment model.
The relationship of depression to homicide has been overlooked in clinical psychiatry. The authors report on six homicidal depressed control compare them with nonhomicidal depressed control subjects. They also analyze data from 81 case summaries found elsewhere in the literature. Their preliminary data suggest that homicidal depressed patients are more likely to have a personality disorder, to have been physically abused as a child, to abuse alcohol or drugs, and to be suicidal than are nonhomicidal depressed patients. In homicidal patients, the event precipitating the depression is more likely to be sexual infidelity, either real or fantasized.
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A zymographic technique for the detection of inhibitors of plasminogen activators has been applied to the analysis of plasma. Two inhibitors have been demonstrated; one inhibited plasmin with consequent apparent inhibition of urokinase and tissue-type plasminogen activator activity; it was identified as alpha 2-antiplasmin. The second inhibitor, as yet unidentified, had a molecular weight of about 40K. It inhibited urokinase and tissue-type plasminogen activator but had no effect on plasmin.
We have developed an enzyme-linked immunosorbent assay (ELISA) to measure antibody production in cell suspensions using highly sensitive avidin-biotinylated peroxidase (ABC) reagents. The cells are serially diluted in media and placed directly on a standard antigen-coated microtiter plate for 6 h, and the plate is then washed and processed to determine the bound antibody. The amount of antibody detected is reduced by puromycin indicating in vitro synthesis. Standard errors of the means of optical density readings of replicate samples are less than 10%. The background readings and readings obtained using non-immune cells are negligible, demonstrating no significant contamination by endogenous peroxidases.
Prostatic calculi are rare in children, infrequent below age 40, and common in males over 50. They may be solitary but usually occur in clusters and are associated with some other disease process (nodular hyperplasia, prostatic carcinoma, metabolic abnormalities). They are most often asymptomatic; however, symptoms that may be attributable to prostatic calculi include reduction of the urinary stream, prostatism, and intense lower back and leg pain. Treatment may be accomplished by transurethral resection, but prostatectomy is the best means to insure complete removal. Prostatic calculi may form by two related mechanisms with obstruction and stasis of prostatic fluid as central entities in both. These mechanisms are calcification of corpora amylacea and simple precipitation of prostatic secretion. They may arise spontaneously, initiating an inflammatory reaction that contributes to their growth, or they may arise as the consequence of another pathologic situation producing acinar obstruction. It appears that infection probably occurs secondary to stone formation.
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All young patients in the Grampian area attending the lymphoma review clinic who had received first line treatment for Hodgkin's disease and had attained complete remission without subsequent relapse were studied between 1980 and 1983. Chemotherapy with MVPP (mustine, vinblastine, procarbazine, and prednisolone) had more severe effects on the fertility of men than that of women; younger women and those taking oral contraceptives were more likely to retain fertility than those over 30 or not taking the pill at the time of chemotherapy, but these two effects could not be differentiated. Premature menopause was common after treatment with MVPP. Mantle radiotherapy had no discernible effect on gonadal function.
An inhibitor of plasminogen activator has been identified in human platelets by the technique of sodium dodecyl sulphate polyacrylamide gel electrophoresis and zymography. The inhibitor has a molecular weight of about 40 000 and is distinct from known plasma protease inhibitors. It is associated almost exclusively with platelets, with only trace amounts in platelet free plasma. The inhibitor is released during platelet aggregation or in vitro coagulation. This inhibitor inhibits both tissue type plasminogen activator and urokinase but has no effect on plasmin. It forms a 1:1 complex with tissue type plasminogen activator, which retains activity detectable under the analytical conditions used. A similar complex with urokinase either forms less readily or retains less activity.
The Association of Plastic Manufacturers in Europe maintains a register of all cases of angiosarcoma of the liver (ASL) resulting from exposure to vinyl chloride monomer (VCM). This register has recorded all known VCM related cases of the disease worldwide that have been histologically confirmed. Although likely to be incomplete, it is the most comprehensive tabulation of such cases available and, by the end of 1984, 118 men had been registered. The information from analysis of the cases currently on the register is used to make an approximate projection of the number of cases to be expected in the future. The conclusion from this projection is that the industry is reaching the halfway stage in the appearance of VCM related ASL.