Search PubMed⌕ Search

Biomedical subjects

T Smith

Publications and source records attributed to T Smith.

At least 397 records · Page 22Linked to original sources
PubMed1995

Suppression of experimental allergic encephalomyelitis in the Lewis rat by the matrix metalloproteinase inhibitor Ro31-9790.

Matrix metalloproteinases (MMPs) are implicated in the tissue destruction associated with inflammatory demyelinating diseases such as multiple sclerosis. The effect of a hydroxamate inhibitor of MMPs, Ro31-9790, on inflammatory demyelination was assessed in two acute models of experimental allergic encephalomyelitis (EAE). Daily intraperitoneal injections of Ro31-9790 (50 mg kg-1), beginning either at the time of disease induction or from day 3 post induction, significantly reduced the clinical severity of adoptively transferred EAE. Administration of the inhibitor from the day of induction of active EAE prevented disease onset in 9/10 animals. However, in a repeat study, in which clinical disease was much more severe in the vesicle treated animals, the inhibitor was less effective. Clinical signs and CNS histopathology correlated well, with greater numbers of inflammatory lesions associated with increased disease severity. The present study confirms a role for then MMP cascade in inflammation in EAE.

Animals↗
PubMed1995

Changes in linoleic acid metabolism and membrane fatty acids of LLC-PK cells in culture induced by 5 alpha-cholestane-3 beta,5,6 beta-triol.

The aim of this study was to investigate the effect of the oxysterol 5 alpha-cholestane-3 beta,5,6 beta-triol (triol) on the metabolism of linoleic acid (18:2n-6) to arachidonic acid (20:4n-6) and on the cell membrane fatty acid composition. Porcine kidney cells were incubated in medium with or without 10 microgram(s)/mL of triol for 24 h, then incubated for 1, 6, or 12 h in a medium which contained 50 muM of either [14C] linoleic acid or unlabeled linoleic acid. The cellular uptake of [14C] linoleic acid was significantly higher in the triol-treated cells than in control cells. After 1- and 6-h incubations despite the increase of [14C] linoleic acid pool size in the triol-treated cells, neither total n-6 polyunsaturated fatty acids (PUFA) metabolites nor arachidonic acid were increased in the triol-treated cells as compared to the control cells, but trienoic acids accumulated to a greater extent in the triol-treated cells. Therefore, the ratios of n-6 PUFA metabolites vs. pool size of linoleic acid and of tetraenoic acids vs. dienoic acids were significantly decreased in triol-treated cells as compared to the control cells. The cellular fatty acid composition also showed that linoleic acid percentage was significantly increased while arachidonic acid percentage was significantly decreased in the triol-treated cells, and that the accumulation of trienoic acids (18:3n-6 + 20:3n-6) observed from the [14C] linoleic acid experiment was due solely to increased 20:3n-6 content. This latter finding indicates that a decrease of elongase activity by triol is unlikely. Our results also showed that the triol-treated cells had a lower level of free cholesterol but higher levels of phospholipid and triol in their membranes, suggesting that triol displaced free cholesterol from the cell membrane.

Animals↗
PubMed1995

Mapping the densities of malaria vectors within a single village.

Small scale spatial variation and temporal heterogeneity in mosquito densities can have important consequences for disease transmission, but the extreme variation which is observed in populations of malaria vectors makes it difficult to obtain good predictions of densities for short time periods over limited areas. We have applied Bayesian techniques derived for use in cancer epidemiology in order to map densities of Anopheles gambiae s.l. and A. funestus in a Tanzanian village where there is intense transmission of Plasmodium falciparum malaria. Estimates derived in this way should prove useful in vector population biology and in improving estimates of exposure-response relationships of the human host to malaria. The same methods can be applied in other fields of animal ecology.

Animals↗
PubMed1995

Sclerosing of recurrent lymphangioma using OK-432.

The authors present two cases of lymphangioma of the cervicofacial region, treated with a new investigational drug in North America, OK-432 (picibanil), a sclerosing agent intralesionally injected. Both patients had been treated surgically and had recurrence of the tumor. Intralesional injection of OK-432 without aspiration was employed for the first patient, and after aspiration in the second patient. A change in consistency of the tumor, manifested by softening, was followed by marked shrinkage. No complication either locally or systemically has occurred during the follow-up period (10 to 16 months). In both cases, satisfactory results were obtained, resulting in definite reduction in size and improvement in cosmetic appearance. The authors recommend OK-432 intralesional injection for surgically challenging lymphangioma. Their results support those of a recent Japanese study using OK-432 as sclerosing therapy for unresectable lymphangioma.

Adolescent↗
PubMed1995

Duodenal trichobezoar caused by compression of the superior mesenteric artery.

Trichobezoars can occur in young women who have a history of trichotillomania, trichophagia, gastric dysmotility, and psychiatric dysfunction. A 6-year-old anorexic girl presented with a fixed right-upper-quadrant abdominal mass. Exploratory celiotomy for a duodenal trichobezoar led to removal of the large foreign body, via a duodenotomy, and prompted a Ladd procedure, in which the duodenum was moved from beneath the compressing superior mesenteric artery to relieve underlying duodenal narrowing.

Bezoars↗
PubMed1995

Evaluation of a PCR assay for detection of Mycobacterium tuberculosis in clinical specimens.

A polymerase chain reaction (PCR) assay for detection of M. tuberculosis was optimized for application to clinical specimens, which were prepared for amplification by boiling in buffer. The buffer contained a synthetic DNA fragment to determine if DNA amplification from the individual prepared specimens was subject to inhibition because of substances present in the specimen, or by the process of specimen preparation or storage. The PCR test was less sensitive than direct microscopy (75% as against 87.5%) and had a specificity of 97%. Invalid results due to inhibition of amplification occurred in 12% of specimens. Incorporation of the internal standard into the specimen preparation buffer ensures that any step in the process which inhibits DNA amplification is detected in the failure of amplification of the internal standard. The use of internal standard in this way should be considered in developing diagnostic protocols.

Base Sequence↗
PubMed1995

The sensitive detection of fluorescently labelled PCR products using an automated detection system.

The polymerase chain reaction plays a central role in many detection assays and methods to improve the sensitivity and specificity of these detection systems are constantly being explored. In this study we investigated the use of an automated laser fluorescent system (ALF) in the context of DNA-based diagnostics for pathogenic bacteria. PCR products were generated using species-specific primer sets, one of which was labelled with a 5' fluorescein. PCR products with a fluorescent label were detected on line with an ALF DNA sequencer and the sensitivity of detection was found to be comparable to that for DNA probe hybridization with a radioactive probe. The technology was successfully applied to the detection of Mycobacterium tuberculosis supplemented into sputum samples and to the detection of listeria in paraffin-embedded tissue samples.

Base Sequence↗
PubMed1995

Gene flow and cross-mating in Plasmodium falciparum in households in a Tanzanian village.

The diversity of the genes encoding 2 merozoite surface proteins (MSP-1 and MSP-2) of Plasmodium falciparum has been examined in parasites infecting members of 4 households in a village in Tanzania. The polymerase chain reaction (PCR) was used to characterize allelic variants of these genes by the sizes and sequences of regions of tandemly repeated bases in each gene. In each household extensive polymorphism was detected among parasites in the inhabitants and in infected mosquitoes caught in their houses. Similar frequencies of the alleles of these genes were observed in all households. Capture-recapture data indicated that both Anopheles gambiae and A. funestus freely dispersed among households in the hamlet. The results confirm that cross-mating and gene flow occur extensively among the parasites, and are discussed within the context of spatial clustering of natural populations of P. falciparum.

Alleles↗
PubMed1995

Determination of digestible energy values and fermentabilities of dietary fibre supplements: a European interlaboratory study in vivo.

The performance of methods to determine energy conversion factors for dietary fibre (DF) supplements and fermentability (D) values of their non-starch polysaccharides (NSP) was investigated. Heats of combustion, digestible energy (DE) and D values were determined on five DF supplements in five European laboratories on five separate occasions. In each instance the DF supplements were fed to juvenile male Wistar rats at two doses, 50 and 100 g/kg basal diet, for 3 weeks with food and faeces collected in the 3rd week. Among-laboratory variations in heats of combustion (delta Hc) were < 2%. DE values (kJ/g dry weight) at the upper and lower doses respectively were: 10.4 and 9.9 for a high-methoxyl apple pectin, 9.5 and 9.4 for a sugar-beet DF supplement, 12.2 and 12.7 for soyabean DF supplement, 3.8 and 4.0 for maize bran, and 0.3 and 0.3 for Solka-floc cellulose. Variations among laboratories, among occasions and among animals were < 1, < 2 and < 2.5 kJ/g respectively. The among-occasion: among-laboratory variance ratio for DE was 0.5, suggesting the method performed equally well in all laboratories. There was no evidence of learning of fatigue or fatigue in the performance of the method. D values were also independent of dose and at the high and lower doses were: pectin 0.92 and 0.95, sugar-beet NSP 0.68 and 0.68, soyabean NSP 0.86 and 0.88, maize bran 0.17 and 0.18, cellulose 0.07 and 0.06. Among-laboratory variance tended to increase with decreasing fermentability and ranged from 0.03 to 0.18. The DE and D data were not significantly different from a previously proposed relationship DE = 0.7 x delta Hc x D, where delta Hc is the heat of combustion of the supplement. We conclude that while the among-laboratory variation in the D of difficult-to-ferment NSP is too large for the reliable prediction of energy value the method for the direction determination of DE is both reproducible and repeatable, that DE is independent of dosage of DF supplement up to 100 g/kg diet, and that it is safe to discriminate between energy values with a precision of 3 kJ/g. The conversion of both DE and D to net metabolizable energy for the purpose of food labelling, tables and databases is described.

Animals↗
PubMed1995

The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. I. Malariometric indices and immunity.

The epidemiological features of malaria were studied through seven community-based surveys in a population of 4000 in the Wosera area, East Sepik Province, Papua New Guinea. Prevalence of parasitaemia (all species, all ages) was 60%. Plasmodium falciparum was the predominant species in all surveys (55%), followed by P. vivax (25%) and P. malariae (20%). The highest prevalence for asexual forms of P. falciparum occurred in the 5-9-year age group, whereas P. falciparum gametocytaemia and P. vivax parasitaemia were observed most frequently in the 1-4-year age group and P. malariae in the 10-15-year age group. Mean densities of all species decreased with age except for that of P. malariae, which was lower in children aged < 1 year than in those aged 1-4 years. The prevalence of enlarged spleen was 57% in children and 10% in adults and closely matched the corresponding age-related parasite rate. Seroprevalence of antibody to the major merozoite surface antigen 2 rapidly increased with age, with > 90% of individuals older than 5 years being positive. Malariological indices showed irregular changes over time but there was no clear-cut seasonal pattern. The geographical distribution of these indices and immune responses was not uniform within the study area. Bednet use and drug consumption were negatively correlated with malariometric indices. Identification of significant temporal and local variations in malaria endemicity is important for the design and evaluation of intervention studies, including field trials of an antimalarial vaccine.

Adolescent↗
PubMed1995

The epidemiology of malaria in the Wosera area, East Sepik Province, Papua New Guinea, in preparation for vaccine trials. II. Mortality and morbidity.

Malaria mortality and morbidity were studied in a rural population of 4000 in the Wosera area, East Sepik Province, Papua New Guinea. Malaria accounted for 4.9% of the 162 deaths investigated by verbal autopsy and for 12.2% of the 49 deaths assessed through medical records. Malaria was the first cause of death in children aged 0.5-4 years. Of the 7795 subjects interviewed and bled during six cross-sectional community-based surveys, children of 1-4 years had the highest malaria-related morbidity. In this age group, point prevalences of fever, fever associated with parasitaemia, and fever plus Plasmodium falciparum (Pf) parasitaemia > or = 10,000 parasites/microliters blood were 5%, 4.1% and 1.5%, respectively. The corresponding figures for adults were 2%, 0.9% and 0.1%, respectively. The calculation of attributable fraction (AF) using a multiple logistic regression model showed that malaria accounted for 0.44 of all fevers in children of 1-4 years and 0.08 of the fevers in adults. Prevalence data derived from the AF estimate were compared with those calculated using different accepted density thresholds. The prevalences which best approximated the results from the logistic regression model were obtained using parasitaemia cut-offs of > or = 1000 Pf parasites/microliter in children aged 1-4 years and adults older than 19 years and of > or = 10,000 parasites/microliter in those aged 5-19 years. Prevalence of fever associated with parasitaemia was highly seasonal, with a peak at the beginning of the wet season. The geographical distribution of malaria morbidity was not uniform. The measurement of malaria-related morbidity, the identification of significant seasonal and local variation as well as the assessment of different methods of defining a clinical episode of Pf malaria are crucial for the design and evaluation of intervention studies, including field trials of antimalarial vaccines.

Adolescent↗
PubMed1995

Development of factor-score-based models to explain and predict maximal box-lifting performance.

The objectives of the study were threefold: (1) to develop factor-score-based models to predict maximum mass on a box-lifting task using multiple regressions; (2) to compare predictive and explanatory powers of factor-score-based models to models derived from data-level variables; and (3) to apply these findings to ergonomic research and practical problem-solving situations. Forty-eight volunteers (25 women and 23 men) completed a maximal box-lifting task and a maximal isoinertial lifting test on an Incremental Lifting Machine (ILM). Dynamic data collected during isoinertial testing were summarized into 32 lift parameters, and then subjected to principal components analyses using the 'FACTOR PROCEDURE' from the Statistical Analysis System (SAS). Factor scores were calculated for each participant on each of the four factors comprising the final solution, and multiple regression equations for men, women and combined data were generated using the 'GENERAL LINEAR MODELS' procedure from SAS. Results revealed that prediction of box-lifting performance was optimized when regression equations were developed using numerous data-level variables as predictors, i.e., all 32 lift parameters and ILM mass. In comparison, explanation was enhanced but predictive capabilities were reduced when linear models were formed using ILM mass and the factor scores derived from analyses of isoinertial lifting. The use of variables loading on the factors gave slightly increased predictive power than did the factor-score-based models. Similar trends in predictive and explanatory powers appeared when the data were analysed according to gender. Ergonomic applications of factor-score-based models were discussed with regard to ongoing research as well as to practical problem-solving situations. It was concluded that the advantages and usefulness of factor-score-based models warranted their inclusion in future investigations of lifting performance.

Adult↗
PubMed1995

Physiological and perceived exertion responses to six modes of submaximal exercise.

In order to compare the cardiovascular and perceived exertion responses to 6 modes of exercise, 10 male recreational exercisers were habituated to treadmill jogging, stationary skiing, shuffle skiing, stepping, stationary cycling, and stationary rowing. After following a specific dietary preparation, each participant performed a 20-min exercise bout at a constant 14-rating of perceived exertion (RPE) followed by a second exercise bout at 60% of mode-specific peak oxygen consumption (VO2peak). On the 14-RPE trial, oxygen consumption (VO2) and oxygen pulse were significantly higher during jogging than during other exercise modes, and oxygen pulse was higher during skiing than during shuffle skiing. On the 60% VO2peak bout, oxygen pulse was significantly higher during jogging than during shuffle skiing, cycling and rowing. Ratings of perceived exertion were significantly higher during cycling than during jogging. These results indicated that a variety of exercise modes can be used to develop fitness, but jogging may induce a slightly more favorable VO2-to-RPE relationship.

Adult↗
PubMed1995

Pulsatile versus nonpulsatile flow. No difference in cerebral blood flow or metabolism during normothermic cardiopulmonary bypass in rabbits.

BACKGROUND: Although pulsatile and nonpulsatile cardiopulmonary bypass (CPB) do not differentially affect cerebral blood flow (CBF) or metabolism during hypothermia, studies suggest pulsatile CPB may result in greater CBF than nonpulsatile CPB under normothermic conditions. Consequently, nonpulsatile flow may contribute to poorer neurologic outcome observed in some studies of normothermic CPB. This study compared CBF and cerebral metabolic rate for oxygen (CMRO2) between pulsatile and nonpulsatile CPB at 37 degrees C. METHODS: In experiment A, 16 anesthetized New Zealand white rabbits were randomized to one of two pulsatile CPB groups based on pump systolic ejection period (100 and 140 ms, respectively). Each animal was perfused at 37 degrees C for 30 min at each of two pulse rates (150 and 250 pulse/min, respectively). This scheme created four different arterial pressure waveforms. At the end of each perfusion period, arterial pressure waveform, arterial and cerebral venous oxygen content, CBF (microspheres), and CMRO2 (Fick) were measured. In experiment B, 22 rabbits were randomized to pulsatile (100-ms ejection period, 250 pulse/min) or nonpulsatile CPB at 37 degrees C. At 30 and 60 min of CPB, physiologic measurements were made as before. RESULTS: In experiment A, CBF and CMRO2 were independent of ejection period and pulse rate. Thus, all four waveforms were physiologically equivalent. In experiment B, CBF did not differ between pulsatile and nonpulsatile CPB (72 +/- 6 vs. 77 +/- 9 ml.100 g-1.min-1, respectively (median +/- quartile deviation)). CMRO2 did not differ between pulsatile and nonpulsatile CPB (4.7 +/- 0.5 vs. 4.1 +/- 0.6 ml O2.100 g-1.min-1, respectively) and decreased slightly (0.4 +/- 0.4 ml O2.100 g-1.min-1) between measurements. CONCLUSIONS: During CPB in rabbits at 37 degrees C, neither CBF nor CMRO2 is affected by arterial pulsation. The absence of pulsation per se is not responsible for the small decreases in CMRO2 observed during CPB.

Anesthesia↗
PubMed1995

pH-stat management reduces the cerebral metabolic rate for oxygen during profound hypothermia (17 degrees C). A study during cardiopulmonary bypass in rabbits.

BACKGROUND: Greater cerebral metabolic suppression may increase the brain's tolerance to ischemia. Previous studies examining the magnitude of metabolic suppression afforded by profound hypothermia suggest that the greater arterial carbon dioxide tension of pH-stat management may increase metabolic suppression when compared with alpha-stat management. METHODS: New Zealand White rabbits, anesthetized with fentanyl and diazepam, were maintained during cardiopulmonary bypass (CPB) at a brain temperature of 17 degrees C with alpha-stat (group A, n = 9) or pH-stat (group B, n = 9) management. Measurements of brain temperature, systemic hemodynamics, arterial and cerebral venous blood gases and oxygen content, cerebral blood flow (CBF) (radiolabeled microspheres), and cerebral metabolic rate for oxygen (CMRO2) (Fick) were made in each animal at 65 and 95 min of CPB. To control for arterial pressure and CBF differences between techniques, additional rabbits underwent CPB at 17 degrees C. In group C (alpha-stat, n = 8), arterial pressure was decreased with nitroglycerin to values observed with pH-stat management. In group D (pH-stat, n = 8), arterial pressure was increased with angiotensin II to values observed with alpha-stat management. In groups C and D, CBF and CMRO2 were determined before (65 min of CPB) and after (95 min of CPB) arterial pressure manipulation. RESULTS: In groups A (alpha-stat) and B (pH-stat), arterial pressure; hemispheric CBF (44 +/- 17 vs. 21 +/- 4 ml.100 g-1.min-1 [median +/- quartile deviation]; P = 0.017); and CMRO2 (0.54 +/- 0.13 vs. 0.32 +/- 0.10 ml O2 x 100 g-1.min-1; P = 0.0015) were greater in alpha-stat than in pH-stat animals, respectively. As a result of arterial pressure manipulation, in groups C (alpha-stat) and D (pH-stat) neither arterial pressure (75 +/- 2 vs. 78 +/- 2 mmHg) nor hemispheric CBF (40 +/- 10 vs. 48 +/- 6 ml.100 g-1.min-1; P = 0.21) differed between alpha-stat and pH-stat management, respectively. Nevertheless, CMRO2 was greater in alpha-stat than in pH-stat animals (0.71 +/- 0.10 vs. 0.45 +/- 0.10 ml O2 x 100g-1.min-1, respectively; P = 0.002). CONCLUSIONS: At 17 degrees C, CMRO2 with pH-stat management is 35-40% less than that with alpha-stat management and is independent of CBF or arterial pressure differences between the techniques.

Acid-Base Equilibrium↗
PubMed1995

Computer-controlled epidural infusion to targeted cerebrospinal fluid concentrations in humans. Clonidine.

BACKGROUND: Pharmacokinetically designed infusions have been demonstrated to achieve rapidly and maintain desired concentrations of drug in plasma after intravenous administration. In this study we tested whether a similar approach, targeting concentrations in cerebrospinal fluid (CSF), could be used with epidural administration of the alpha 2-adrenergic analgesic clonidine. METHODS: After institutional review board approval and informed consent had been obtained, seven healthy volunteers received a clonidine infusion through a lower lumbar epidural catheter. Infusion of clonidine (10 micrograms/ml) was controlled by the STANPUMP program for sequential 75-min periods to targeted CSF clonidine concentrations of 25, 50, 75, and 150 ng/ml. Before reprogramming to the next higher targeted concentration, mean arterial blood pressure and heart rate were measured; blood was obtained for clonidine and catecholamine assays; and visual analog score for sedation and pain to immersion of foot and hand in ice water were obtained. CSF was collected during infusion with an indwelling lumbar intrathecal catheter and was analyzed for clonidine, catecholamines, and acetylcholine. RESULTS: CSF clonidine concentrations rapidly increased and were maintained at steady values with the stepped infusion, although observed concentrations were consistently greater than targeted. The relation between CSF clonidine concentration and analgesia in the foot was similar to that previously observed after epidural bolus administration. Clonidine also was associated with concentration-dependent sedation; decreased mean arterial blood pressure, heart rate, and CSF norepinephrine concentration; and increased CSF acetylcholine concentration. CONCLUSIONS: This study suggests that pharmacokinetically designed infusions of drugs in the epidural space in humans can maintain steady concentrations of drug in CSF. In addition to providing a useful tool for investigation of mechanisms of action and drug interactions, this technique may improve analgesia and diminish side effects from epidurally administered analgesics.

Adult↗
PubMed1995

Diaspirin cross-linked hemoglobin does not increase brain oxygen consumption during hypothermic cardiopulmonary bypass in rabbits.

BACKGROUND: Decreased erythrocyte deformability due to cardiopulmonary bypass (CPB) and/or hypothermia, may result in brain capillary beds that have decreased erythrocyte transit, resulting in a generalized impairment of brain oxygenation during CPB. Because brain capillary plasma flow continues even when erythrocyte flow is absent, the authors' hypothesized augmentation of plasma oxygen content with a non-erythrocyte-associated oxygen transport molecule would increase brain oxygen uptake during hypothermic CPB. METHODS: Anesthetized New Zealand white rabbits, maintained on CPB at 27 degrees C, were randomized to one of three groups. In group 1 (n = 13), plasma oxygen content was increased by administration of alpha-alpha diaspirin cross-linked hemoglobin. In this group, pretreatment with 0.5 mg/kg verapamil was necessary to prevent hypertension. In group 2 (n = 13), alpha-alpha diaspirin cross-linked hemoglobin was not administered, but verapamil was given as before (control). In group 3 (n = 13), neither alpha-alpha diaspirin cross-linked hemoglobin nor verapamil was administered (control). At 60 min of CPB, cerebral blood flow (microspheres) and cerebral metabolic rate for oxygen (Fick) were determined. RESULTS: Systemic physiologic variables did not differ among groups. Although total arterial oxygen content was equivalent in all groups (approximately 12.1 ml O2/dl), the alpha-alpha diaspirin cross-linked hemoglobin group had a much greater proportion of the total arterial oxygen content present in a non-erythrocyte-associated form, 29 +/- 5% versus 6 +/- 2% and 5 +/- 3%, in groups 2 and 3, respectively. Nevertheless, neither cerebral blood flow (approximately 34 ml.100g-1.min-1) nor cerebral metabolic rate for oxygen (approximately 1.2 ml O2.100g-1.min-1) differed among groups. CONCLUSIONS: Because oxygen was equally available to the brain in all groups, independent of whether oxygen was associated with erythrocytes or not, it was concluded that erythrocyte/capillary interactions do not limit oxygen transfer from blood to brain during moderately hypothermic CPB. The hypertensive response to alpha-alpha diaspirin cross-linked hemoglobin during CPB is probably a result of nitric oxide scavenging.

Animals↗