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Biomedical subjects

T L Smith

Publications and source records attributed to T L Smith.

At least 217 records · Page 12Linked to original sources
PubMed1994

Drug use among primary alcoholic veterans.

Many people with alcohol dependence use other drugs. However, not much is known about the relationship between their past drug use (not necessarily dependence) and their prognosis following treatment. The goal of this study is first to determine the drug use rates among primary alcoholic men and then to evaluate the possible relationship between past drug use and future alcohol or drug use relapse. As a result, 630 primary alcoholic veterans were recruited from a 28-day inpatient Alcohol and Drug Treatment Program at the San Diego VA Medical Center. Among them, almost two-thirds also had a history of drug use. Subjects were divided into the following four groups which were determined by their lifetime drug use histories: Group I (N = 226) consisted of drug abstainers, Group 2 (N = 142) was made up of alcoholics who had used only marijuana, Group 3 (N = 210) contained stimulant users who had never used opiates, and Group 4 (N = 52) included all opiate users. Comparisons of the four groups at a 3-month follow-up revealed that alcoholic men who had a history of stimulant or opiate use (Groups 3 and 4) were more likely to have had a drug use relapse. However, the four groups had similar alcohol relapse rates.

Adult↗
PubMed1994

Long-term systemic hemodynamic effects of cotinine in rats.

Cigarette smoking has been epidemiologically correlated with lower BP in humans, despite the acute BP effects of nicotine. Cotinine, a primary metabolite of nicotine, has been suggested as a mediator of the BP-lowering effect of smoking. To determine the cardiovascular effects of cotinine itself, arterial BP was monitored continuously in chronically instrumented Sprague-Dawley rats before, during, and after 14 days of intraarterial (i.a.) infusion of cotinine or placebo. Cardiovascular data were collected and analyzed by microcomputer for diurnal changes and for light- and dark-cycle averages. Heart rate (HR) was higher in both precotinine and placebo groups during the dark cycle than during the light cycle. HR was significantly lower (p < 0.025) during cotinine infusion in the cotinine group as compared with placebo. Five days after cotinine infusion, however, HR was not different from that of placebo controls. Arterial BP was not different between cotinine- and placebo-treated rats at any time period. The difference between HR but not arterial BP suggested that baroreceptor activity might differ after cotinine administration. Baroreceptor activity, assessed by analysis of HR changes evoked by phenylephrine, did not differ before and during cotinine administration, however. We conclude that cotinine did not decrease BP in rats under the present experimental conditions, but that cotinine was probably responsible for the observed bradycardia.

Animals↗
PubMed1994

Combined effects of magnesium deficiency and an atherogenic level of low density lipoprotein on uptake and metabolism of low density lipoprotein by cultured human endothelial cells. I. Biochemical data.

The effects of magnesium deficiency on uptake and metabolism of low density lipoprotein (LDL) were investigated using human arterial endothelial cells cultured in media containing various concentrations of magnesium (100-1000 microM) and a high concentration of LDL (2 mg LDL cholesterol/ml) labelled with [3H]cholesteryl linoleate. The LDL uptake was time-dependent and increased for up to 8 h in both the magnesium-deficient and magnesium-sufficient treatments. The extent of LDL uptake progressively increased with the decrease in magnesium concentration of the medium. Surface-bound LDL also increased in a similar manner during the incubation but less extensively than the LDL uptake. The majority of radioactivity from internalized LDL was detected in unesterified cholesterol at all time points in both the magnesium deficiency and sufficiency groups. Only small amounts of radioactivity were found in cholesteryl esters. These findings indicate that most LDL taken up by the cells was rapidly hydrolysed but not readily re-esterified. The lack of re-esterification may be due to a relative deficiency of acyl-CoA:cholesterol acyltransferase (ACAT) and the presence of large amounts of unesterified cholesterol.

Analysis of Variance↗
PubMed1994

Combined effects of magnesium deficiency and an atherogenic level of low density lipoprotein on uptake and metabolism of low density lipoprotein by cultured human endothelial cells. II. Electron microscopic data.

The effects of magnesium deficiency on low density lipoprotein (LDL) transport by cultured endothelial cells with a high concentration of LDL (2 mg of LDL cholesterol/ml) were investigated by electron microscopy and by counting the radioactivity of [3H]-LDL transported across an endothelial monolayer grown on culture plate inserts. Electron microscopic examination showed that the number of pits/vesicles in the apical side was time-dependently increased for 24 h in both magnesium-deficient and magnesium-sufficient groups with the exception of 1 h under magnesium sufficiency. The number of pits/vesicles in the basal side was also increased for 8 h in both groups, though there was a decrease at 24 h in the two groups. No difference between either magnesium group at the same time point was statistically significant. [3H]-LDL transport was also time-dependently increased in both magnesium-deficient and magnesium-sufficient groups. In contrast to the results obtained by electron microscopy, the amount of LDL transported under magnesium deficiency was much larger for 24 h than under magnesium sufficiency. Differences in LDL transport between magnesium groups were statistically significant at 4 and 8 h. This finding indicates that magnesium deficiency increases LDL transport across the endothelial monolayer. The increase may be due to energy-dependent movement across endothelial cells, energy-independent movement between cells, or both. However, we conclude that magnesium deficiency increases the energy-dependent LDL transport to some degree since intercellular gap formations were rarely observed in either magnesium group. This LDL transported to the subendothelial space may lead to LDL accumulation and initiate atherosclerosis.

Arteriosclerosis↗
PubMed1993

The order of administration of chemotherapy and radiation and its effect on the local control of operable breast cancer.

BACKGROUND: A delay in administration of radiation therapy has been suggested to increase the risk of local recurrence after breast-conserving surgery. METHODS: The data were retrospectively reviewed from 552 patients in whom treatment consisted of total mastectomy (n = 467) or segmental mastectomy (n = 85), irradiation, and combination chemotherapy. Of these, 463 patients received radiation therapy first, and 89 received chemotherapy first. The pattern of failures was compared between the subgroups according to the order of administration chemotherapy and irradiation and its effect on the local control of disease. RESULTS: The median follow-up time of the local mastectomy subgroup was 133 months; of the segmental mastectomy subgroup, it was 39 months. The incidence of locoregional failure within each subgroup was not affected by the order in which the chemotherapy and irradiation were administered. CONCLUSIONS: These data suggest that delaying irradiation in an effort to reduce the risk of systemic relapse does not increase the risk of local failure.

Breast Neoplasms↗
PubMed1993

Desensitization of neurokinin A receptors expressed by B82 fibroblasts.

After chronic exposure to neurokinin A, a time-dependent and recoverable desensitization of inositol monophosphate accumulation occurred in B82 fibroblasts transfected with cDNAs encoding for the bovine stomach NK2 receptor. Desensitized cells also showed decreased Ca2+ mobilization. While NK2 receptor antagonists had no effect on inositol monophosphate accumulation, substance P and senktide both produced a small degree of desensitization.

Animals↗
PubMed1993

New skeletal muscle model for the longitudinal study of alterations in microcirculation following contusion and cryotherapy.

This preliminary report describes the use of a rat model developed to study in vivo the effect of anesthesia, contusion, and cryotherapy on skeletal muscle microcirculation by use of an implanted chamber. The diameters of arterioles and venules within the chamber were determined by photomicroscopy in the contusion study and by compound videomicroscopy in the anesthesia study; microvascular perfusion was determined by laser Doppler fluxmetry (LDF). Combined ketamine and xylazine anesthesia significantly reduced (P < 0.05) arteriolar and venular diameters by 32.4% and 37.8%, respectively, and average LDF measurements by 36.1%. Contusion significantly increased arteriolar diameters over baseline values (P < 0.05); cryotherapy did not alter arteriolar diameters but increased venular diameters (P < 0.05). It is hypothesized that this increase in venular diameter may, by increasing the surface area available for reabsorption, explain one mechanism by which cryotherapy decreases the edema of contusion. Use of this model should help to advance the understanding of microcirculatory dynamics following contusion and cryotherapy.

Anesthesia↗
PubMed1993

The efficacy of a hospital dry cleaning cycle in disinfecting material contaminated with bacteria and viruses.

It is not known how efficiently a standard dry cleaning cycle can kill bacteria or viruses. In-situ experiments were carried out to determine the cidal activity of such a cycle using perchloroethylene solvent against five clinical bacterial isolates and a DNA bacteriophage. Viable counts of bacteria recovered from material after dry cleaning were reduced by 3-8 logs, with up to 10(3) colony forming units (cfu) surviving per strip. Numbers of bacteriophage were only reduced by 10-100 fold. The resistance of the bacteriophage to solvent and heat (60 degrees C) was compared with that of polio and herpes simplex viruses in vitro. Polio virus and bacteriophage, but not herpes simplex virus, survived exposure to perchloroethylene at room temperature for 40 min. Dry cleaning with perchloroethylene is not bactericidal and is particularly poorly virucidal for non-enveloped viruses.

Bacteria↗
PubMed1993

Tachyphylaxis in cardiovascular responses to cocaine in conscious rats.

Tachyphylaxis has been shown to occur in human cardiovascular responses to cocaine. The present study was designed to establish a response curve for cardiovascular parameters in conscious, chronically instrumented rats and to investigate the degree of tachyphylaxis occurring in these parameters after repeated doses of cocaine. Cardiovascular parameters evaluated included arterial pressure, heart rate (HR), and electrocardiogram (ECG). Administration of low doses (0.0625 mg/kg) of cocaine caused significant increases in arterial pressure. Changes in HR accompanying intravenous (i.v.) cocaine were usually biphasic, characterized by an initial reflex bradycardia, followed by a secondary tachycardia lasting several minutes. Tachyphylaxis was observed in the cardiovascular responses when cocaine was administered repetitively at 5-min intervals. This tachyphylaxis was not apparent when the interval between cocaine infusions was extended to 2 h. The mechanism responsible for the tachyphylaxis is hypothesized to be mediated by the presynaptic alpha 2-receptors. Conscious animals were very sensitive to i.v. cocaine administration, and tachyphylaxis to repeated cocaine administration was observed. Both observations must be considered when interpreting cardiovascular studies using cocaine.

Adrenergic alpha-Antagonists↗
PubMed1993

Subjective predictions of outcome among alcoholics.

This study examines the importance of Subjective Staff Ratings as predictors of the 3- and 12- month outcomes in 375 male primary alcoholic inpatients. For short-term outcome, while combinations of more usual predictors including two aspects of the pretreatment drinking history, evidence of a stable personal relationship, prior alcoholic hospitalizations, employment status, and posttreatment recovery home placement explained up to 5% of the variance on three measures of short-term outcome, Subjective Ratings alone explained up to 6%. The combination of Subjective Ratings and objective historical data explained up to 9% of the variance. The data indicate that it is difficult to accurately predict short term outcome among primary alcoholics, that the Subjective Ratings of prognosis by the treatment staff are important predictors of short-term outcome which do not overlap greatly with more traditional predictors, but that these ratings appear to add little to the longer term outcome prediction.

Adult↗
PubMed1993

Thrombin and bradykinin initiate discrete endothelial solute permeability mechanisms.

This study documents the discrete solute permeability mechanisms associated with physiologically high concentrations of human alpha-thrombin and bradykinin stimulation of bovine pulmonary artery endothelial cell (BPAEC) monolayers using fluorescein isothiocyanate-hydroxyethyl starch macromolecules. Agonist-induced alterations of intracellular free calcium ([Ca2+]i) using fura-2 acetoxymethyl ester were also measured. BPAEC monolayers showed restricted diffusion consistent with a small-pore (approximately 150 A) radius under baseline conditions. Thrombin produced a major increase in monolayer permeability that was greatest for solute molecular radii (ae) > 100 A. This effect was associated with the exposure of the large (approximately 2,000 A) pores of the filter support by 50- to 1,050-microns2 open areas between approximately 0.5% of the adjacent endothelial cells. This heterogeneous endothelial barrier of parallel large- and small-pore transport pathways permitted solute convection with free diffusion across a few large pores to dominate the restricted diffusion of most apparently unperturbed endothelial junctions. Bradykinin produced a small, transient elevation in monolayer permeability to ae < 35 A, consistent with an increase in the number of small pores or a decrease in path length of this transport pathway. The bradykinin- and thrombin-induced peak elevations in [Ca2+]i were inversely associated with the degree of increased monolayer solute permeability, and enzymatically inhibited thrombin produced none of these effects. These data show that bradykinin and human alpha-thrombin represent two distinct classes of endothelial cell agonists that initiate discrete solute permeability mechanisms.

Animals↗
PubMed1993

Clinical course of alcoholism in 636 male inpatients.

OBJECTIVE: This study was undertaken to determine the relative order of appearance of symptoms in alcohol dependence. METHOD: The age at which 21 alcohol-related major life events first occurred was investigated in 636 male alcohol-dependent inpatients through a standardized, structured personal interview with each subject and at least one resource person. RESULTS: A general pattern of first occurrence of these events was observed. Heavy drinking escalated further when the subjects were in their late 20s, followed by evidence of interference with functioning in multiple life areas in the early 30s, a subsequent perception of loss of control, and then an intensification of social and job-related problems, along with evidence of deterioration in body systems, in the mid- to late 30s. Similar patterns of problems emerged when the alcoholic subjects were divided into subgroups based on onset of alcohol dependence before or after age 30, presence or absence of a family history of alcoholism, and presence or absence of additional psychiatric disorders. CONCLUSIONS: These data indicate that there is a typical progression of events related to alcohol dependence. This information can be useful for clinicians in their work with patients and for teachers and researchers as well.

Adult↗
PubMed1993

Control of the mucosal microcirculation in the upper respiratory tract.

This study was designed to investigate the regulatory mechanisms of the mucosal microvascular network in the upper respiratory tract. Tracheal mucosal circulation was observed using a specially constructed chamber that allowed direct microscopic visualization of mucosal arterioles. Solutions of increasing hypertonicity (500 and 900 mOsm) applied to the tracheal epithelium resulted in increasing dilation of the underlying mucosal arterioles (p < 0.001). N(omega)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/L), a specific inhibitor of nitric oxide synthesis, added to a hypertonic solution inhibited dilation of mucosal arterioles (p < 0.001). Addition of the substrate for nitric oxide synthesis, L-arginine (0.6 mmol/L) to the hypertonic solution containing L-NAME resulted in dilation of mucosal arterioles once again. These data demonstrate that nitric oxide is a crucial mediator in the response of mucosal arterioles to the hypertonic stimulus presented to the epithelial surface of the trachea. Further elucidation of the control of the mucosal microcirculation in the upper respiratory tract could be implemented in new treatment for pathologic processes of the upper respiratory tract such as mucosal congestion and edema.

Analysis of Variance↗
PubMed1993

Cytotoxicity of oxysterols on cultured smooth muscle cells from human umbilical arteries.

The lethal effect of 25- and 26-hydroxycholesterol on smooth muscle cells derived from human umbilical arteries was investigated. The extent of cellular death corresponded with increasing oxysterol concentrations and incubation times. Incubation of the cells with 0.5, 2.5, or 10 micrograms/ml of 25- or 26-hydroxycholesterol revealed a proportionality between the degree of cellular death and oxysterol concentration over the 5 days of the experiment. Correlation coefficients among the degree of cellular death, the exposing period, and oxysterol concentration were significantly different (P < 0.05). However, none of these changes were noted in the smooth muscle cells cultured for 5 days in a medium containing the same concentration of cholesterol or 0.5% ethanol. An increase in the concentration of either serum or cholesterol in the culture medium did not significantly reduce the cytotoxicity of 2.5 micrograms/ml of 26-hydroxycholesterol. The results of this study suggest that oxysterols have an injurious effect on arterial cells, and that the injurious effect could not be altered by cholesterol, which was present at a serum concentration 12 times higher than that of oxysterols.

Cell Death↗
PubMed1993

Stress testing in the evaluation of upper-extremity perfusion.

Stress testing is an important element in the evaluation of upper extremity vascular perfusion. Advances in noninvasive testing provide mechanisms to evaluate the static structural characteristics of the arterial system, to define patient and nonpatient vessels to identify areas of thrombosis or occlusion, to evaluate arterial wall motility and elasticity, and to observe the nutritional capillary bed. To understand upper-extremity vascular function, however, some form of stress testing is crucial. The techniques discussed previously continue to evolve and serve only as examples of the potential of noninvasive tests evaluated before, during, and after stress. Stress testing provides techniques that allow us to understand the functional components of vascular perfusion and to monitor our attempts at interventions.

Adult↗
PubMed1992

The effect of experimentally induced diabetes mellitus on the lipid order and composition of rat cerebral microvessels.

To determine whether diabetes mellitus alters the lipid order and composition of cerebral microvessels, streptozotocin-induced diabetic rats were studied after 5 weeks of chronic hyperglycemia. Diabetes did not affect membrane order or the thermotropic transition temperature of cerebral microvessels as determined from the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH). The cholesterol, phospholipid and fatty acid composition of isolated cerebral microvessels was also not significantly affected in diabetic rats. On the other hand, the cerebral microvessels of diabetic rats had significantly increased concentration of lipid peroxidation byproducts, namely conjugated dienes (the calculated O.D./mg phospholipids was 6.98 +/- 0.52 in controls and 11.82 +/- 0.40 in diabetic rats (P < 0.01). The accumulation of conjugated dienes in cerebral microvessels of diabetic rats in the absence of an alteration in the availability of substrates for peroxidation is consistent with the hypothesis that diabetes mellitus is a disease state which is associated with increased free radical activity. Increased oxidative damage may contribute to the changes in the blood-brain barrier observed in animal models of diabetes.

Animals↗
PubMed1992

Independent validation of APACHE II severity of illness score for predicting mortality in patients with breast cancer admitted to the intensive care unit.

BACKGROUND: To determine the validity and predictive accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE II) scoring system for severity of illness by comparing the actual hospital mortality with the predicted mortality for patients with breast cancer admitted to the intensive care unit (ICU). METHODS: APACHE II scores were calculated based on retrospective evaluation of the medical records of 52 patients with breast cancer who received ICU care. The relationships between hospital mortality and APACHE II scores, number of sites of metastatic disease, duration of metastatic disease, number of chemotherapeutic regimens given for metastatic disease, presence of neutropenia or thrombocytopenia, age, reason for ICU admission, and length of ICU stay were assessed. RESULTS: Twenty-two patients (42%) died during the hospital stay during in which they were admitted to the ICU. Predicted mortality based on a logistic regression model using APACHE II scores was 21 patients (40%). APACHE II specificity was 87%; sensitivity was 54%. There were significant relationships between presence of metastatic disease, number of metastatic sites, reason for ICU admission, and length of ICU stay. Patients with more than two sites of metastatic disease and those with respiratory failure had particularly poor chances of survival. Regression analysis incorporating the number of sites of metastatic disease, reason for ICU admission (whether for a pulmonary or a cardiovascular problem), and APACHE II score suggested that APACHE II could predict hospital survival. CONCLUSIONS: This retrospective study showed that APACHE II scores were associated with hospital mortality in patients with breast cancer who were admitted to ICU. The number of metastatic sites and the type of major organ system failure were also associated with outcome. Regression analysis suggested that APACHE II scores were independently associated with survival outcome.

Adult↗