Biomedical subjects
Publications and source records attributed to G Brown.
A hospital marketing model is proposed for use as a framework for applying marketing strategy and concepts to hospitals. The cells of the model, primarily summarizing the many decisions of the marketing management process as can be applied to hospitals, are justified by the health care marketing literature.
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Positron emission tomography is a powerful tool for the absolute quantification of injected positron emitting radiotracer concentration within tissues in vivo. Very detailed spatiotemporal data can be obtained without biopsy sampling. Most chemotherapeutic agents can be labelled with a positron emitter, and human tissue and tumour pharmacokinetics can be obtained non-invasively. Its main limitations are the inability to discriminate metabolites, the short half-life of the isotopes used and the specialized equipment required. Despite this, PET has the potential to make a major contribution in the study of the pharmacokinetics of anti-cancer drugs.
To determine if specific sets of dysfunctional attitudes were related to suicidal ideation, the 100-item Dysfunctional Attitude Scale (DAS) was administered to 908 psychiatric outpatients along with the Beck Depression Inventory (BDI), Hopelessness Scale (BHS), Self-Concept Test (BST), and Scale for Suicide Ideation (SSI). The SSI was used to classify the outpatients into 97 (10.7%) suicide ideators and 811 (89.3%) nonideators, and the DAS was scored for nine subscales described by Beck, Brown, Steer, and Weissman (1991). None of the DAS subscales discriminated the ideators and nonideators or was significantly related to SSI total scores of the suicide ideators after controlling for sex, age, diagnosis of a mood or panic disorder, comorbidity, presence of a personality disorder, a history of a past suicide attempt, the BDI, the BHS, and the BST. The contributions of sets of dysfunctional attitudes for identifying and explaining suicidal ideation were overshadowed by a history of a past suicide attempt and hopelessness.
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The hypothesis that an infusion of recombinant tissue-type plasminogen activator (rt-PA) maintained for up to 24 hours could prevent reocclusion after early coronary patency had been established was evaluated in patients with acute myocardial infarction. The rt-PA studied was an investigational double chain rt-PA (Duteplase, Burroughs Wellcome Co.), administered according to body weight. Coronary patency was documented in 139 of 213 patients who had 90-minute angiograms recorded after an initial lytic dose of rt-PA. In these responders a further 90-minute infusion at one third the initial lytic dose was given before assignment to 1 of 4 maintenance dose rates (0.012, 0.024, 0.036, 0.048 MIU/kg/hour) which were continued for the subsequent 9 to 21 hours. The principal end point was the status of the infarct-related coronary artery 12 to 24 hours after the start of therapy, and before termination of rt-PA, in patients with initially patent vessels at 90 minutes. Of the 103 responders with repeat angiograms after a 9 to 21 hour maintenance infusion of rt-PA, a total of 17 (16.5%) patients reoccluded across all doses administered. There was no significant relationship between the maintenance dose rate and the incidence of reocclusion. However, there was strong association between total dose of rt-PA administered and the incidence (16%) of serious or life-threatening bleeding exclusive of surgery. Other factors associated with serious bleeding included low body weight, female gender, and total duration of rt-PA infusion. Reocclusion was independent of the 90-minute Thrombolysis in Myocardial Infarction trial perfusion grade and diameter of infarct vessel. Rethrombosis after establishment of early patency after rt-PA remains a significant problem that is unaffected by sustained rt-PA infusion in doses that can be tolerated.
A homogeneous population of undifferentiated myeloid blast cells was purified from human fetal liver by rosette sedimentation of erythroblasts and macrophages, after coating these cells with monoclonal antibodies, followed by a cell elutriation step. The undifferentiated blast cells were maintained in culture, in a serum-free medium containing 1 mg l-1 inositol, by the presence of a high concentration of interleukin-3 (100 U ml-1). This allowed equilibrium labelling of cells with [2-3H]myo-inositol and analysis of the concentrations of inositol metabolites. The myeloid blast cells contained high concentrations of an unidentified inositol metabolite, possibly sn-glycero-3-phospho-1-inositol (GroPIns, 22 microM), inositol monophosphate (InsP, 16 microM), an unidentified inositol bisphosphate (InsP2, 9.4 microM), inositol pentakisphosphate (InsP5, 37 microM) and inositol hexakisphosphate (InsP6, 31 microM). These high concentrations are similar to those reported in the promyeloid cell line, HL60. Treatment of the blast cells with 10 nM phorbol myristate acetate (PMA) resulted in rapid differentiation of 48% of the cells towards monocytes. Notable changes in the levels of inositol metabolites included an increase in the putative GroPIns peak (to 73 microM) and decreases in the concentrations of InsP4 (from 4 microM to 1 microM) and InsP5 (to 21 microM). These changes in response to PMA, with the exception of the rise in the putative GroPIns, are similar to those reported in HL60 cells undergoing monocyte differentiation. These observations suggest that the abundant inositol polyphosphates may have an as yet unknown role in myeloid differentiation.
It is established that receptor-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate is an essential signalling reaction in the responses of many haemopoietic cells to stimuli: examples include platelet activation, antigen-driven initiation of cell proliferation in mature B and T lymphocytes and histamine release by mast cells, and chemotaxis and oxygen radical generation by neutrophils. However, the roles of inositol lipids and phosphates in the development of haemopoietic and immune cells are less well understood. This paper discusses three such situations: the sequential employment of phosphatidylinositol 4,5-bisphosphate hydrolysis and cyclic AMP accumulation as two signals essential to the action of the B lymphocyte-stimulatory cytokine interleukin 4; the involvement of antigen receptor-triggered inositol lipid hydrolysis in apoptotic elimination of immature anti-self T lymphocytes in the fetal mouse thymus; and the possible role of changes in the levels of abundant inositol polyphosphates in the differentiation of HL-60 promyelocytic cells and of normal human myeloid blast cells.
A major 19 kD cytosolic protein (p19) has been described in a number of cell systems with respect to its rapid phosphorylation when protein kinase C is activated and has been proposed as a key substrate of this enzyme. Phosphorylation of p19 occurs when the growth of cells is affected by 12-O-tetradecanoylphorbol-13-acetate (TPA) and it has been proposed that increased phosphorylation of p19 relates to the cessation of cell growth. This study delineates precisely the relationship between p19 phosphorylation changes in the growth and differentiation status of cells. Changes in the levels of two phosphorylated forms of p19 were assessed in HL-60 promyelocytic cells and a variant HL-60 cell line which stopped growing and differentiated in response to TPA and were compared to changes seen in HL-60 variant lines which merely growth arrested when treated with TPA. In lines which either did or did not differentiate, in response to TPA, the p19 protein was rapidly and transiently phosphorylated. Thus, this alteration in the phosphorylation status of p19 is associated with the process of growth arrest and not related to the onset of cell differentiation. The p19 protein and the enzymes which effect its phosphorylation status modulate the growth of cells and possible disregulation of p19 and/or its kinases and phosphatases is of interest as regards the leukaemic transformation of cells.
Unipolar depression is frequently a recurrent or chronic disorder. In studies on predicting its course, outcomes are typically linked to either psychiatric features or stressful life events. In order to integrate the 2 approaches, 51 unipolar patients were assessed periodically over at least 1 year for symptoms, stressful events, and chronic stressors. It was hypothesized that adverse family history and early age of onset impair role functioning and coping capabilities, thereby contributing to stressful circumstances that predict severity of depressive reactions. Results of causal modeling analyses supported a model in which background factors were associated with severity of depressive outcomes as mediated by their effects on stress variables. Such a model implicates the self-perpetuating nature of clinical depression, both for the individual and across generations.
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The role of an increase in total peripheral resistance (TPR) and the contribution of angiotensin II (ANG II) to the hypertension induced by reduced uterine perfusion pressure (RUPP) was explored in pregnant rabbits. On the 22nd day of gestation, a catheter and a microthermocouple were placed in the aorta to measure mean arterial pressure (MAP) and cardiac output (CO), respectively. Three days later, RUPP was induced by a clip on the aorta proximal to the ovarian and distal to the renal arteries. Mean arterial pressure distal to the clip (uterine perfusion pressure) was reduced to 56 +/- 8% (mean +/- SD) of the initial level. Twenty-four hours later, MAP rose from 65 +/- 3 to 84 +/- 11 mm Hg; CO index decreased from 207 +/- 18 to 169 +/- 27 ml/min/kg; and TPR index increased from 0.32 +/- 0.03 to 0.51 +/- 0.08 mm Hg kg/ml/min, respectively (n = 7, all p less than 0.01). Sham-operated pregnant rabbits (n = 7) and non-P rabbits (n = 5) with a comparable distal aortic pressure reduction experienced no change in MAP or CO. Infusion of a receptor antagonist of angiotensin II (Sar1,Ile8-Ang II, 1 microgram/kg/min for 20 min) decreased MAP in sham-operated pregnant rabbits from 64 +/- 6 to 54 +/- 6 mm Hg (p less than 0.01) but did not change MAP in RUPP hypertensive rabbits (86 +/- 9 mm Hg before and 87 +/- 8 at the end of infusion, n = 6). These data indicate that RUPP in pregnant rabbits leads to a high resistance form of hypertension in which the formation of Ang II is not increased.
Eleven independent transgenic canola (Brassica napus ssp. oleifera L. cv. Westar and Regent) lines were evaluated in the field. The plants carried a neomycin phosphotransferase (NPTII) gene for kanamycin resistance that was introduced via Agrobacterium-mediated transformation. NPTII enzyme assays, Southern blot by hybridizations and progeny analysis, confirmed the stable, heritable integration and expression of the introduced NPTII gene. A number of agronomic characteristics evaluated under field conditions, including maturity yield, and oil and protein content, were all statistically comparable between the transformed and nontransforemd platns. These results indicate that canola can be genetically engineered successfully, and that the Agrobacterium-based transformation system employed does not induced any adverse effects on the intrinsic agronomic and qualitative traits critical to the agricultural industry.
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Diabetes mellitus is associated with a significant reduction in the serum concentration of Mg2+. Several studies have suggested that hypomagnesemia may be implicated in the etiology of diabetic complications; however, no mechanism has been proposed. This study demonstrates that Mg2+ is a positive effector of inositol transport and is capable of promoting a 2.5-fold increase in the affinity of the transporter for inositol. Analysis of the kinetics of inositol transport shows that, at physiological concentrations of inositol, the reductions in Mg2+ concentrations that occur in diabetic patients would result in a significant decline in the rate of inositol transport (1.5- to 2-fold). We suggest that hypomagnesemia may be linked to the development of diabetic complications via reduction in the rate of inositol transport and subsequent intracellular inositol depletion. This assertion allows hypomagnesemia and the polyol theory to be unified into one mechanistic model for the development of diabetic complications.