Contraceptive choice.
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Contraceptives, Oral, Hormonal↗
Biomedical subjects
G W Smith
Publications and source records attributed to G W Smith.
Proton relaxation times in bleomycin-induced lung injury.
Pulmonary fibrosis and inflammation induced in mice by biweekly injection of low doses (20 mg/kg) of bleomycin chronically administered subcutaneously was associated with a significant increase in T2 values measured in vitro (54.6 +/- 20.7 ms vs. 36.2 +/- 3.8 ms in controls). T1 values, however, were not altered significantly (613 +/- 124.6 ms vs. 666 +/- 105.7 ms in controls). Lung water content did not change (79.1 +/- 2.5% vs. 78.4 +/- 0.98% in controls, NS). Water content to dry weight ratio in the control group (3.63 +/- 0.212) did not differ significantly from that in the experimental group clinically treated with bleomycin (3.84 +/- .618). However, morphometric and histologic analysis indicated that in 71% of the chronically treated mice, there was marked pulmonary fibrosis (mean area of involvement 3.5 +/- 8.1% vs. 0.25 +/- 0.15% in controls, P less than .01). In addition, there was marked increase in pulmonary cellularity and infiltration by lymphocytes and macrophages (mean area of macrophage infiltration 8.71 +/- 13.256% vs. 1.17 +/- 1.404% in controls). The alteration in T2 in bleomycin damaged lung occurred in the absence of change in overall water content. However, the change in cellularity indicates an alteration of water distribution between the cellular, intravascular, and interstitial components induced by the measurable fibrotic and inflammatory response to bleomycin.
Animals↗
Inhibition of Uptake1 by dopexamine hydrochloride in vitro.
1 Dopexamine hydrochloride, a compound under evaluation for the acute treatment of heart failure, was examined in vitro for its ability to prevent neuronal uptake of noradrenaline. 2 Despite possessing only weak beta 1-adrenoceptor agonist activity in paced guinea-pig left atria, dopexamine hydrochloride was only 23 times less potent than isoprenaline in augmenting responses of field-stimulated atrial preparations. 3 This potent effect was not observed in field-stimulated atria depleted of noradrenaline by reserpine and in the presence of cocaine was greatly reduced (1 microM) or abolished (50 microM). 4 Dopexamine hydrochloride (3 microM) potentiated the inotropic effect of exogenous noradrenaline in paced atria, thereby resembling cocaine (10 microM) and dopamine (30 microM), both of which are known inhibitors of Uptake. 5 The sodium-dependent uptake of [3H]-noradrenaline into rabbit brain synaptosomes was prevented by dopexamine hydrochloride (IC50 26 nM) and cocaine (IC50 108 nM), as well as by two other catecholamines used in the treatment of heart failure, dopamine (IC50 270 nM) and dobutamine (IC50 380 nM). 6 The cardiac stimulant effect of dopexamine hydrochloride reported in dogs and in patients with heart failure, may therefore be due in part to potentiation of endogenous catecholamines.
Adrenergic Agonists↗
The cardiovascular actions of dopexamine hydrochloride, an agonist at dopamine receptors and beta 2-adrenoceptors in the dog.
The receptor pharmacology of the cardiovascular effects of dopexamine hydrochloride in the anaesthetized dog (given by i.v. infusion of 3 X 10(-9)-10(-7) mol kg-1 min-1) has been analysed by the use of selective receptor antagonists and of ganglionic blockade. The increases in cardiac output, contractility, and rate were antagonized by the beta 2-adrenoceptor antagonist, ICI 118551. Renal blood flow rose secondary to reduction in renal vascular resistance and this was antagonized by SCH 23390, a highly selective DA1-receptor antagonist. Peripheral vasodilation and reduction of blood pressure were mediated by a combination of DA1- and DA2-receptor and beta 2-adrenoceptor stimulation. In a separate group of dogs, the cardiac stimulant effects of dopexamine HCl were partially reflex and were reduced by ganglion block, revealing responses due to stimulation of cardiac beta 2-adrenoceptors. Thus the beta 2-adrenoceptor agonist action of dopexamine HCl is not only partly responsible for afterload reduction but also leads to direct cardiac stimulation. From its cardiovascular profile, dopexamine HCl is likely to be of use in acute treatment of heart failure.
Adrenergic Agonists↗
Lack of inotropic selectivity of phosphodiesterase enzyme inhibitors in-vitro.
Phosphodiesterase enzyme (PDE) inhibitors form a diverse category of chemical structures which display positive inotropic activity, but it is unclear as to how force/rate selective these are on the heart. In this study several recently developed PDE inhibitors, almost all of which are selective for the cardiac PDE III isoenzyme, were compared with the xanthine PDE inhibitor IBMX and with ouabain and the direct and indirect adenylate cyclase activators, forskolin and isoprenaline, respectively. These compounds were active in increasing paced guinea-pig left atrial force, the order of potency being: isoprenaline greater than ouabain greater than forskolin greater than pimobendan greater than IBMX greater than sulmazole greater than buquineran greater than carbazeran greater than milrinone greater than piroximone greater than amrinone. Ro 13-6438 and enoximone were however, both inactive. With the exception of buquineran and carbazeran, which produced bradycardia and were therefore force specific, all of the recently discovered PDE inhibitors increased the rate of contraction of the right atria and they were rate selective to the same extent as IBMX, isoprenaline and forskolin. Sulmazole, the only force selective PDE inhibitor of the compounds studied, was intermediate between IBMX and ouabain in force/rate selectivity and pimobendan showed no selectivity. Since both these agents also possess other actions, then these results suggest that in general, PDE III inhibitors do not show advantageous force selectivity in guinea-pig atria.
Animals↗
Comparative trial of cefuroxime axetil in recurrent urinary tract infections illustrating importance of 6-week follow-up.
Women with recurrent urinary tract infections treated with cefuroxime axetil (500 or 250 mg twice daily) for 7 days had a higher relapse rate when tested 6 weeks after the start of treatment than those given amoxycillin (250 mg three times daily). The poor performance of cefuroxime axetil is explained by variable bioavailability.
Amoxicillin↗
Conversion by new treatment modalities of nonresectable to resectable hepatocellular cancer.
Eleven patients with hepatocellular cancer had nonresectable lesions, ten as determined by laparotomy and one by computed tomographic (CT) evidence of inferior vena caval invasion. These patients were treated with a variety of new modalities, particularly radiolabeled antiferritin antibodies. Following treatment, seven of the 11 patients were considered to have converted their lesions to possible resectability. Six patients had complete resections, and one patient was partially resected. All patients had the common features of either nodular massive or nodular multifocal hepatocellular cancer. Relative to the patient's initial status, the quality of life remains high, and a new approach in the treatment of the nodular form of nonresectable hepatoma has been demonstrated. The present rate of such conversion to resectability is unknown. However, with further advances in radiolabeled antibody therapy, these results offer a new opportunity in the management of hepatocellular cancer.
Antibodies, Monoclonal↗
Should business office employees be exempt from staffing reductions?
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Employment↗
Resident, employee needs come first.
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Consumer Behavior↗
Effect of therapy on bleeding rates in gastrointestinal angiodysplasia.
Sixteen patients with gastrointestinal angiodysplasia requiring transfusion were treated with surgical resection, endoscopic electrocautery, or transfusion alone. Pre- and post-therapy transfusion requirements in each group were compared to gauge the efficacy of each therapy. No superiority of any treatment could be shown statistically. The majority of patients had multiple angiodysplastic lesions throughout the gastrointestinal tract, and, accordingly, complete resolution of bleeding after therapy occurred in fewer than one-half of the patients.
Aged↗
Physicians as politicians and statesmen. An unaccustomed role. Can it be done?
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Government↗
Hemodialysis-associated hemorrhagic cholecystitis.
Hemorrhagic complications of hemodialysis have been recognized and described in many viscera and anatomic locations. In addition, hepatobiliary pathology is a frequent finding in hemodialysis patients. An adult male is reported as the first case of spontaneous intracholecystic hemorrhage treated by urgent cholecystectomy.
Aged↗
Obturation obstruction in a cocaine smuggler.
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Adult↗
Preservation of mucus in situ in rat colon.
Mucus, a hydrated complex consisting mainly of glycoproteins, forms a layer over the epithelial surface of the gastrointestinal tract. The usual preparative procedures for histological and scanning electron microscopic examination of the gut result in the loss or distortion of this mucus layer. Careful evaluation of two new methods reported to stabilize the mucus layer showed that acrolein vapor did not provide adequate fixation, but application of heat-inactivated antiserum raised in rabbits against rat colon mucus reliably preserved a continuous layer closely adherent to the epithelium. This stabilized layer is continuous with the mucus in the colonic crypts.
Animals↗
Diffusion of butyrate through pig colonic mucus in vitro.
Using a modified equilibrium dialysis cell the rate of diffusion of butyrate through pig colonic mucus has been compared with that through other gels and unstirred layers. Relative diffusion coefficients were calculated for each layer. Layers of 8% polyacrylamide, and of caecal, mid-colonic and terminal colonic mucus, had coefficients that were 50-60% of the apparent free diffusion coefficient for butyrate, determined using layers made up of Millipore filters alone. The apparent free diffusion coefficients for butyrate (layers of agarose or filters) were 70% of previously determined values in the literature. This discrepancy can be explained by elements of the experimental procedure. All mucus layers differed significantly from layers of 2% agarose and Millipore filters but were not significantly different from layers of 8% polyacrylamide or from each other. Diffusion coefficients for butyrate in the mucus samples correlated with water content and carbohydrate content but had no relationship to protein content. The rate of diffusion of butyrate in colonic mucus layers was significantly reduced when compared with unstirred layers (P less than 0.05). Whether this has an effect on the butyrate supply to colonocytes in vitro and whether mucus in colonic disease behaves differently are subjects for further investigation.
Animals↗
Pathogenesis of nonocclusive ischemic colitis.
The nonocclusive component of ischemic colitis in anesthetized pigs was mimicked using cardiogenic shock produced by pericardial tamponade. Increases in pericardial pressure produced decreases in arterial pressure (PA) and cardiac output (CO), with corresponding rises in total peripheral resistance (i.e., cardiogenic shock). This was associated with marked reductions in blood flow through the inferior mesenteric artery (IMA), due primarily to disproportionate increases in IMA vascular resistance. Levels of plasma renin activity correlated closely with these changes in mesenteric hemodynamics. Confirmed, total alpha adrenergic blockade with phenoxybenzamine failed to block this selective mesenteric vasoconstriction, while ablation of the renin-angiotensin axis with captopril completely abolished it, thereby ameliorating the colonic ischemia. Central intravenous infusions of pathophysiologic levels of angiotensin II, without tamponade, mimicked the response to shock seen with tamponade alone. In an additional group of pigs, 4 hours of sustained shock (tamponade) followed by 2 hours of normotension (release of tamponade and resuscitation) produced lesions characteristic of ischemic colitis, including full-thickness mucosal ulceration. Such lesions were ameliorated significantly in pigs in which the renin-angiotensin system had been ablated by bilateral nephrectomy. Nonocclusive ischemic colitis appears to be mediated primarily by a remarkable sensitivity of the colonic vasculature to the renin-angiotensin axis.
Animals↗
Location of bacteria in the mid-colon of the rat.
The distribution of microorganisms in the mid-colon of the rat was studied by light and scanning electron microscopy. An antiserum against rat colon mucus was used to stabilize the mucus in situ. In samples not incubated with antiserum, the mucus disintegrated and contracted into patchy strands only partly covering the luminal surface of the colon. Bacteria were seen within fecal pellets, tangled among the strands of mucus, and scattered on the epithelial surface. However, when incubated with antiserum, mucus almost completely filled the lumen and coated the fecal pellets. Bacteria in these stabilized preparations were limited mainly to the fecal pellets, and there were small numbers scattered in the luminal mucus, but none were observed on the epithelial surface or within the crypts. Latex particles introduced into the lumen with the antiserum or with phosphate-buffered saline showed the same distribution as the bacteria. These findings are at variance with previous reports that organisms occur in abundance in the mucous layer, adjacent to cell surfaces, and inside crypts. Our results suggest that conventional preparation for microscopy without prior stabilization of the mucus in situ may lead to artifactual redistribution of microorganisms and emphasize the importance of mucus in maintaining mucosal-floral homeostasis in the colon.
Animals↗