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Biomedical subjects

D C Brown

Publications and source records attributed to D C Brown.

At least 127 records · Page 7Linked to original sources

Growth-promoting effect of recombinant interleukin 1 and tumor necrosis factor for a human astrocytoma cell line.

IL 1 can exhibit dichotomous effects in the sense that it is cytotoxic for certain cells, although growth promoting for other cells. Because IL 1 is growth promoting for astrocytes, but cytotoxic for melanoma cells, the current investigation evaluated the effect of IL 1 upon astrocytomas. The human astrocytoma U373 was found to incorporate [3H]thymidine after exposure to recombinant human IL 1 alpha and IL 1 beta and murine IL 1 alpha. Surprisingly, U373 also incorporated [3H]thymidine after exposure to recombinant TNF. The response of the U373 to IL 1 may be used as a simple and sensitive assay for IL 1.

Astrocytoma↗

Survival of patients with acute renal failure requiring dialysis after open heart surgery: early prognostic indicators.

We analyzed pre- and postoperative data from 36 consecutive patients, who developed acute renal failure requiring hemodialysis after open heart surgery, to determine which factors predicted survival. Seventeen patients (47%) survived. Age, sex, preoperative renal dysfunction, severity of underlying heart disease, perioperative myocardial infarction, cardiopulmonary bypass time, and oliguria did not influence outcome (by univariate analysis). However, the number and type of postoperative complications, before the first hemodialysis and 48 hours thereafter, were found to be significant predictors of outcome. Univariate as well as multivariate analysis showed that the highest mortality rate was associated with the presence of respiratory failure, central nervous system dysfunction, hypotension, and infection (48 hours after first hemodialysis). Thirty-three (92%) of the 36 patients were correctly classified as survivors or nonsurvivors based on the presence or absence of any one of three prognostic indicators (three or more complications before the first hemodialysis and persisting 48 hours later; hypotension before the first dialysis and persisting 48 hours later; or central nervous system dysfunction 48 hours after hemodialysis was initiated). We conclude that an assessment of prognosis can be made in such patients as early as 48 hours after the first hemodialysis based on the number and type of complications.

Acute Kidney Injury↗

Use of two-dimensional grid patterns to limit hazardous ambulation in demented patients.

Ambulation into potentially dangerous areas or away from necessary monitoring can be a problem for demented patients and their care providers. Current methods of controlling hazardous ambulation usually involve restraint, medication, locked doors, or physical intervention. Capitalizing on the observation that many demented individuals perceive two-dimensional patterns as barriers, we laid out masking tape in different grid patterns in an attempt to prevent ambulation through exit doors. The baseline condition (no tape) yielded a 98% exit-door contact for 8 demented male patients, but the addition of horizontal grids reduced exit-door contact to 42%. Often, complete prevention occurred at the first experimental trial. Advantages and cautions inherent in this approach to managing wandering by demented patients are discussed.

Aged↗

Is it necessary to embed bone marrow biopsies in plastic for haematological diagnosis?

With the increase in the use of bone marrow trephines for diagnosis have come numerous reports that traditional methods of preparation (by decalcification and embedding in paraffin wax) should be replaced by plastic embedding to avoid decalcification. It has been argued that only by this means can the high quality preparations needed for accurate haematopathological diagnosis be achieved. The present study challenges this viewpoint and argues that with a little extra care and attention conventional paraffin embedding techniques can give equally high quality preparations. Sections prepared in this way meet the diagnostic needs of the haematologist, without requiring a separate technique to be established in the pathology laboratory solely for bone marrow trephines.

Biopsy↗

Cytokeratin expression in smooth muscle and smooth muscle tumours.

The expression of cytokeratin intermediate filaments by a tumour has been accepted as evidence of an epithelial origin. Although there have been anecdotal reports of cytokeratin expression within tissues and neoplasms of non-epithelial origin, particularly muscle, there have been no comprehensive studies of its frequency and distribution. In order to investigate this we have studied 51 cases of normal smooth muscle and benign and malignant smooth muscle tumours using a panel of monoclonal antibodies against a range of intermediate filaments (cytokeratins, desmin and vimentin). Cytokeratin expression was noted overall in 50% of normal, benign and malignant smooth muscle tissues. Such expression tended to have a focal or patchy distribution. No case expressed cytokeratins in the absence of both desmin and vimentin. The implication of these findings for diagnostic immunocytochemistry is that intermediate filaments alone are not completely reliable markers of tumour histogenesis and should be used as part of a larger panel of monoclonal antibodies.

Desmin↗

Dihydroorotase from Escherichia coli. Cloning the pyrC gene and production of tryptic peptide maps.

We have inserted a 1.7-kilobase pair Escherichia coli DNA fragment containing the 1-kilobase pair pyrC gene into the high copy number plasmid pKC16. Dihydroorotase expressed by the pyrC plasmid in E. coli constituted 6.3% of the soluble protein in frozen cell paste. Pure dihydroorotase derived from this frozen cell paste was compared with pure enzyme derived from an E. coli strain lacking the pyrC plasmid: tryptic peptide maps from the two dihydroorotase preparations, produced using reverse-phase high performance liquid chromatography, were indistinguishable. We conclude that the entire pyrC gene is present on the hybrid plasmid and that the dihydroorotase produced from this plasmid is identical to the wild type.

Amidohydrolases↗

Intraocular lens implant exchanges.

We reviewed 23 consecutive cases of intraocular lens implant exchange. Lens dislocation (26%) and chronic intraocular inflammation (26%) were the most frequent indications for lens exchange. Post-exchange vision was best in those eyes treated for inappropriate implant power (100% less than or equal to 20/40), intermediate in dislocation cases (83% less than or equal to 20/40), and poorest in eyes with chronic intraocular inflammation (50% less than or equal to 20/40), even though the inflammation usually improved. Eighty-three percent of the total cases remained within one line of the pre-exchange visual acuity.

Aged↗

The physiological and pharmacological role of presynaptic alpha- and beta-adrenoceptors in man.

Two studies were performed each in six normal volunteers in order to find evidence of either a physiological or pharmacological role of presynaptic alpha- and presynaptic beta-adrenoceptors in man. In Study 1 subjects received a 60 min infusion of guanfacine 3 mg (alpha 2-adrenoceptor agonist) preceded by either idazoxan (alpha 2-adrenoceptor antagonist) or vehicle. Guanfacine reduced plasma noradrenaline concentration by approximately 30% and this fall was not antagonised by the alpha 2-receptor antagonist. The 30-fold increase in plasma growth hormone, measured as a marker of the central action of guanfacine, was almost completely blocked by idazoxan. A comparison of the drug concentrations of idazoxan and guanfacine, together with their relative affinities for alpha 2-adrenoceptors, suggested that the idazoxan could not block the peripheral actions of guanfacine and that these were responsible for the fall in plasma noradrenaline concentration. In Study 2 adrenaline 0.05 micrograms kg-1 min-1 was infused for 80 min preceded by either idazoxan or vehicle. After vehicle, adrenaline caused no change in plasma noradrenaline concentration whereas it rose approximately 25% after administration of idazoxan. This was probably due to unmasking of presynaptic beta-adrenoceptor stimulation by adrenaline when the opposing inhibitory autoreceptor was blocked.

Adrenergic beta-Antagonists↗

Selective alpha 2 receptor blockade facilitates the insulin response to adrenaline but not to glucose in man.

The adrenergic nervous system plays an important role in the control of insulin release and animal work suggests that this is mediated by way of alpha 2 adrenoceptors. A specific alpha 2 adrenoceptor antagonist (idazoxan) is now available for use in man and we have studied its effects on insulin release in normal volunteers (a) during the infusion of adrenaline (0.05 micrograms/kg/min) and (b) after an intravenous dose of glucose (20 g). The infusion of adrenaline alone had no significant effect on insulin release while in the presence of idazoxan, insulin release was markedly stimulated by adrenaline. Despite this, adrenaline-induced hyperglycaemia was unaffected by pretreatment with idazoxan. In the second study, pretreatment with either idazoxan or a specific alpha 1 antagonist (prazosin) had no significant effect on either glucose tolerance, glucose-induced insulin release or glucose-induced suppression of glucagon. Intravenous glucose also had no significant effect on pancreatic polypeptide levels. Therefore the effect of adrenaline on insulin release is mediated by way of inhibitory alpha 2 adrenoceptors in the pancreas, while the release of insulin in response to glucose in a resting subject is independent of the alpha-adrenergic system.

Adult↗

Effect of levamisole treatment on lambing performance of winter housed ewes.

The value of levamisole treatment of ewes housed during the last 10 weeks of pregnancy was studied over four successive years in a lowland flock of 400 ewes. Levamisole treatment, shortly after housing in January, improved the live lambing percentage each year, by an average of nine lambs per 100 ewes mated. Birthweight of lambs was unaffected by the improvement in lamb numbers.

Animals↗

Survey of vomitoxin-contaminated feed grains in midwestern United States, and associated health problems in swine.

During the 1981 corn harvest season in Illinois and surrounding states, cold wet weather enhanced the growth of Fusarium graminearum, with resulting contamination by vomitoxin and, to a lesser extent, zearalenone. Of 342 feed samples analyzed, 274 contained vomitoxin at a concentration ranging from 0.1 to 41.6 ppm (mean, 3.1 ppm) and 40 samples contained zearalenone at a concentration ranging from 0.1 to 8 ppm (mean, 0.66 ppm). Animal health problems and reduced growth performance were observed mainly in swine fed vomitoxin-contaminated rations. The predominant clinical complaints, in decreasing frequency were: reproductive problems (50%), feed refusal (43%), reduced weight gain (25%), diarrhea (17%), death (14%), and emesis (11%).

Animal Feed↗

Hypokalemia from beta2-receptor stimulation by circulating epinephrine.

To determine whether epinephrine-induced hypokalemia is due to beta2-adrenoceptor stimulation, and whether hypokalemia can occur at physiologic concentrations of the agonist, epinephrine was infused into six normal volunteers at a rate of 0.1 microgram per kilogram of body weight per minute. The circulating epinephrine concentration was increased to 1.74 +/- 0.65 ng per milliliter, plasma potassium was reduced by 0.82 +/- 0.19 meq per liter, plasma insulin fell by 12 +/- 4 mU per liter, plasma renin activity was elevated, and tachycardia occurred. Isoproterenol infused at 0.02 micrograms per kilogram per minute caused similar tachycardia (25 beats per minute) and elevation in plasma renin activity (6.0 to 6.5 ng per milliliter per hour), but no hypokalemia. The difference in responses to the two catecholamines was ascribed to the relative beta2-selectivity of epinephrine. This hypothesis was tested in six subjects given infusions of epinephrine (0.05 micrograms per kilogram per minute) after administration of either 2.5 or 5 mg of ICI 118551--a selective beta2-receptor antagonist--or placebo. After placebo, epinephrine infusion elevated the circulating epinephrine concentration and reduced plasma potassium; hypokalemia was prevented by the beta2-antagonist. This drug only partially inhibited the rises in plasma renin and glucose and the shortening of systolic time intervals; there was no tachycardia. Fifteen-fold to 30-fold increases in circulating epinephrine concentration appear to cause hypokalemia by a specific beta2-receptor effect distinct from other actions of epinephrine. This phenomenon may be of physiologic importance after severe myocardial infarction, when similar increases in plasma epinephrine have occurred.

Adult↗