Search PubMed⌕ Search

Biomedical subjects

T Smith

Publications and source records attributed to T Smith.

At least 271 records · Page 15Linked to original sources
PubMed1998

Cerebrovascular relaxation responses to endothelium-dependent and -independent vasodilators after normothermic and hypothermic cardiopulmonary bypass in the rabbit.

BACKGROUND: Cardiopulmonary bypass causes activation of leukocytes and increased concentrations of proinflammatory mediators, which may result in endothelial dysfunction. Because hypothermia attenuates many inflammatory processes, the authors hypothesized that hypothermic cardiopulmonary bypass would be associated with better endothelial function than normothermic cardiopulmonary bypass. METHODS: Isoflurane-anesthetized New Zealand White rabbits were randomized to undergo 90 min of either normothermic (37 degrees C, n=9) or hypothermic (27 degrees C, n=9) cardiopulmonary bypass with terminal rewarming. A third group served as anesthetized normothermic non-cardiopulmonary bypass surgical controls (n=8). Basilar artery and descending thoracic aorta were isolated from each animal. In vitro vessel relaxation responses to increasing concentrations of acetylcholine (which induces endothelial release of nitric oxide) and nitroprusside (which provides exogenous nitric oxide) were measured in phenylephrine-precontracted vessel rings. RESULTS: There were no differences in vessel relaxation responses between normothermic and hypothermic cardiopulmonary bypass groups in basilar artery or aorta. In contrast, basilar arteries from non-cardiopulmonary bypass controls had increased relaxation responses to both acetylcholine (P=0.004) and nitroprusside (P=0.031) compared with the pooled cardiopulmonary bypass animal data. CONCLUSIONS: The authors observed no differences in endothelial or vascular smooth muscle function between normothermic and hypothermic cardiopulmonary bypass groups. Compared with non-cardiopulmonary bypass controls, cardiopulmonary bypass appeared to decrease basilar artery smooth muscle relaxation in response to endogenous and exogenous nitric oxide.

Acetylcholine↗
PubMed1998

An institutional experience with cervical vagus nerve trunk stimulation for medically refractory epilepsy: rationale, technique, and outcome.

OBJECTIVE: Intermittent stimulation of the left cervical vagus nerve trunk is emerging as a novel adjunct in the treatment of medically refractory seizures. We sought to evaluate theoretical and practical issues attendant to this concept. We review the anatomic and physiological background arguing for clinical application of vagus nerve stimulation, discuss salient aspects of patient selection and the nuances of surgical technique, and present our observations of and results from application of the method. METHODS: Each of 18 patients with medically refractory epilepsy and at least six complex partial or secondarily generalized seizures per month underwent placement of a NeuroCybernetic Prosthesis pulse generator (Cyberonics, Webster, TX) in the chest, connected to helical platinum leads applied to the left cervical vagus nerve trunk. The patients were then randomized in a double-blinded fashion to receive either high (presumably therapeutic) or low (presumably less therapeutic) levels of vagus nerve stimulation. Reduction in seizure frequency, global assessments of quality of life, physiological measurements, and adverse events were recorded during a 3-month period. Patients in the low group were then crossed over to high-stimulation paradigms during a 15-month extension trial. RESULTS: All operations were successful, uneventful, and without adverse postoperative sequelae. One patient was excluded from analysis because of inadequate seizure calendars. Of the seven patients initially assigned to high stimulation, the mean reduction in seizure frequency was 71% at 3 months and 81% at 18 months. Five (72%) of these patients had a greater than 75% reduction in seizure frequency, and one (14%) remained seizure-free after more than 1.5 years of follow-up. The mean reduction in seizure frequency among the low-stimulation group was only 6% at 3 months. No serious complications, device failures, or physiological perturbations occurred. CONCLUSION: In our experience, vagus nerve stimulation has proven to be a safe, feasible, and potentially effective method of reducing seizures in select patient populations. However, the elements of strict definition for the application of the method require further study.

Adult↗
PubMed1998

An update of radiopharmaceutical schedules in children.

Proposed radiopharmaceutical schedules based on readily measured parameters (age, height, weight, surface area) have been considered with respect to their applicability in nuclear medicine. Although schedules based on age are considered to be inappropriate, there are valid cases for schedules based on height, weight and surface area. For many radiopharmaceutical studies, the most appropriate schedules are based on weight or surface area. Examination of simple theoretical physical models, including the influence of attenuation, suggests that the optimum administered amounts of radiopharmaceuticals fall mainly within the region bounded by these two schedules. The results of recent clinical studies designed to test the validity of different schedules are summarized. In general, they support the predictions of theoretical models, but also show how simple models can be influenced significantly by the age dependency of radiopharmaceutical biodistribution. The schedule based on surface area (or height) is less likely than that based on weight to require the identification of minimum administered amounts of radiopharmaceutical to preserve image quality in small children. However, recent studies have shown that the most appropriate schedule for regional cerebral blood flow with 99Tcm-HMPAO is that based on weight, without the need for a minimum activity. Paediatric radiation dosimetry is briefly summarized to indicate some recent innovations in methodology. Effective doses per unit of administered radiopharmaceutical (mSv MBq-1) have been calculated using five paediatric phantoms for a number of radiopharmaceuticals commonly used in children. Values of total effective dose resulting from the application of the weight and surface area schedules are presented, based on the adult reference amounts of administered radiopharmaceutical proposed by the Paediatric Task Group of the European Association of Nuclear Medicine. Although some values of effective dose exceed 10 mSv for the surface area schedule, the majority of values are less than 5 mSv.

Body Height↗
PubMed1998

Myocardial dysfunction in the septic rat heart: role of nitric oxide.

Previous studies have demonstrated that sepsis, endotoxin, and cytokine administration cause myocardial dysfunction. Nitric oxide has been implicated in this dysfunction, since in isolated cardiac tissues, dysfunction is prevented when nitric oxide synthase (NOS) inhibitors are present. To determine whether nitric oxide produced by the inducible form of the enzyme (iNOS) contributed to Escherichia coli sepsis-induced myocardial dysfunction, the effects of preventing the induction of the enzyme or inhibiting the activity of the enzyme were determined. Rats, made septic by the injection of E. coil into the dorsal subcutaneous space, demonstrated a decreased intrinsic contractile function when hearts were studied the next day. Perfusion of hearts in vitro with the iNOS inhibitor S-methylisothiourea did not reverse the sepsis-induced contractile dysfunction. However, treatment of animals with S-methylisothiourea or dexamethasone, a glucocorticoid that prevents the synthesis of the iNOS, at the time of induction of sepsis resulted in partial but not complete attenuation of myocardial contractile dysfunction induced by sepsis. Thus, nitric oxide contributed to myocardial dysfunction in an intact animal treated with E. coli but was not the sole factor involved.

Animals↗
PubMed1998

Nonfluoroscopic transseptal catheterization: safety and efficacy of intracardiac echocardiographic guidance.

INTRODUCTION: Recently, there has been a revival in the use of transseptal catheterization due to the development of balloon mitral valvuloplasty and radiofrequency catheter ablation. Complications of transseptal puncture, although rare, can be serious and life-threatening. In the present study, we evaluated the use of intracardiac echocardiography (ICE) as the sole imaging modality to guide transseptal puncture and catheterization. METHODS AND RESULTS: In each animal, 10 transseptal punctures were performed guided solely by ICE. The standard approach to transseptal catheterization using a Brockenbrough needle and long vascular sheath was used except for the use of ICE instead of fluoroscopy. A 6.2-French/12.5-MHz and 9-French/9-MHz ICE catheter was used for imaging. At the end of each study, pathologic evaluation was performed. Transseptal puncture was performed safely, guided solely by ICE, in each of 100 attempts (five attempts guided by each ICE catheter in 10 dogs). While the fossa ovalis was easily visualized with both ICE catheters, the 9-French/9-MHz catheter offered an enhanced field of view. On pathologic evaluation, there was no evidence of perforation of either the right or left atrium outside of the fossa ovalis. CONCLUSION: Both ICE catheters used in this trial allowed for excellent visualization of the fossa ovalis and safe transseptal puncture. Intracardiac echocardiography may be a better imaging modality than fluoroscopy for guiding transseptal catheterization, especially in less experienced hands.

Animals↗
PubMed1998

Near-nerve versus surface electrode recordings of sensory nerve conduction in patients with carpal tunnel syndrome.

OBJECTIVES: The aim of the study was to compare the relative sensitivity of sensory nerve conduction (SNC) recorded with near-nerve needle electrodes and SNC recorded with surface electrodes in demonstrating focal slowing of the median nerve in patients with symptoms of carpal tunnel syndrome (CTS). MATERIALS AND METHODS: Eighty-two consecutive patients with clinical symptoms and signs of CTS were studied prospectively by the same clinical neurophysiologist. Orthodromic near-nerve recording from digits 1 and 3, distal motor latency, and antidromic surface recording from palm to digit 2 and wrist to digit 2 were performed in all patients. Near-nerve recording of the ulnar nerve was done in patients with abnormal median nerve conduction. Patients were compared to controls. RESULTS: Near-nerve SNC was abnormal (slowed velocity or absent response) in 52% of the patients from digit 1 to wrist, in 51% from digit 3 to wrist, and 40% had a prolonged distal motor latency. Surface antidromic SNC was abnormal in 49% from wrist to palm, and in 43% from wrist to digit 2. Statistical analysis revealed no significant difference between the near-nerve method and the surface method. Absent sensory potentials were more common with the surface method. CONCLUSION: As a routine study of CTS patients, the surface technique can be used and the near-nerve technique merely used for patients with absent surface responses.

Adolescent↗
PubMed1998

Localization of leptin binding domain in the leptin receptor.

The leptin receptor is a member of the class I cytokine receptor family and is involved in the control of appetite and body weight. The predicted amino acid sequence of the extracellular region of the cloned leptin receptor differs from that of many other cytokine receptors in that it contains two homologous segments representing potential ligand binding sites. After the analysis of various deletion and substitution mutants of the leptin receptor, we found that the first potential binding motif is not required for leptin binding and receptor activation, whereas modification of the second potential binding motif can lead to inactive receptor mutants. Further deletion analysis generated a minimal binding domain that retains high affinity leptin binding. The leptin binding domain thus has been localized to residues 323-640, which contain the second segment of cytokine receptor domain/fibronectin type 3 domain (residues 428-635). Coexpression of the active isoform of leptin receptor (OB-Rb) with an inactive mutant lacking high affinity leptin binding site led to suppression of the activity mediated by OB-Rb, suggesting that the leptin receptor may exist as a multimeric complex in the absence of leptin.

Amino Acid Sequence↗
PubMed1998

Bacterial oxidation of mercury metal vapor, Hg(0).

We used metalloregulated luciferase reporter fusions and spectroscopic quantification of soluble Hg(II) to determine that the hydroperoxidase-catalase, KatG, of Escherichia coli can oxidize monatomic elemental mercury vapor, Hg(0), to the water-soluble, ionic form, Hg(II). A strain with a mutation in katG and a strain overproducing KatG were used to demonstrate that the amount of Hg(II) formed is proportional to the catalase activity. Hg(0) oxidation was much decreased in stationary-phase cells of a strain lacking KatG, suggesting that the monofunctional hydroperoxidase KatE is less effective at this reaction. Unexpectedly, Hg(0) oxidation also occurred in a strain lacking both KatE and KatG, suggesting that activities other than hydroperoxidases may carry out this reaction. Two typical soil bacteria, Bacillus and Streptomyces, also oxidize Hg(0) to Hg(II). These observations establish for the first time that bacteria can contribute, as do mammals and plants, to the oxidative phase of the global Hg cycle.

Artificial Gene Fusion↗
PubMed1998

The 131-amino-acid repeat region of the essential 39-kilodalton core protein of fowlpox virus FP9, equivalent to vaccinia virus A4L protein, is nonessential and highly immunogenic.

The immunodominant, 39,000-molecular weight core protein (39K protein) of fowlpox virus (FP9 strain), equivalent to the vaccinia virus A4L gene product, contains highly charged domains at each end of the protein and multiple copies of a 12-amino-acid serine-rich repeat sequence in the middle of the protein. Similar repeats were also detected in other fowlpox virus strains, suggesting that they might confer a selective advantage to the virus. The molloscum contagiosum virus homolog (MC107L) also contains repeats, unlike the vaccinia virus protein. The number of repeats in the fowlpox virus protein does not seem to be crucial, since some strains have a different number of repeats, as shown by the difference in the size of the protein in these strains. The repeat region could be deleted, indicating that it is not essential for replication in vitro. It was not possible to delete the entire 39K protein, indicating that it was essential (transcriptional control signals for the flanking genes were left intact). The repeat region is partly responsible for the immunodominance of the protein, but the C-terminal part of the protein also contains highly antigenic linear epitopes. A role for the 39K protein in immune system modulation is discussed.

Amino Acid Sequence↗
PubMed1998

Association of petrochemical exposure with spontaneous abortion.

OBJECTIVES: To assess the association between petrochemical exposure and spontaneous abortion, a retrospective epidemiological study in a large petrochemical complex in Beijing, China was conducted. METHODS: Plant employment records identified 3105 women who were married, were 20-44 years of age, and had never smoked. Of those, 3070 women (98.8%) reported at least one pregnancy. From this group, 2853 (93%) of the women participated in the study. According to their plant employment record, about 57% of these women workers reported occupational exposure to petrochemicals during the first trimester of their pregnancy. Trained interviewers administered a standardised questionnaire to this group of women and their husbands, collecting information on reproductive history, pregnancy outcomes, employment history, occupational exposure, smoking habits, alcohol consumption, indoor air pollution, and demographic variables. The results from the womens' first pregnancies were analysed. RESULTS: There was a significantly increased risk of spontaneous abortion for women working in all of the production plants with frequent exposure to petrochemicals (8.8%; range of 5.8%-9.8%) compared with those working in nonchemical plants (2.2%; range of 0.0%-7.1%). Also, when a comparison was made between exposed and non-exposed groups within each plant, exposure to petrochemicals was consistently associated with an increased risk of spontaneous abortion. The overall odds ratio (OR) was 2.7 (95% confidence interval (95% CI) 1.8 to 3.9) after adjusting for potential confounders. When the analysis was performed with the exposure information obtained from the women' interview responses for (self reported) exposures, the estimated OR for spontaneous abortions was 2.9 (95% CI 2.0 to 4.0). The analysis was repeated by excluding those 452 women who provided inconsistent reports between recalled exposure and work history, and a comparable risk of spontaneous abortion (OR 2.9; 95% CI 2.0 to 4.4) was found. In analyses for exposure to specific chemicals, an increased risk of spontaneous abortion was found with exposure to most chemicals, and the results for benzene (OR 2.5; 95% CI 1.7 to 3.7), gasoline (OR 1.8; 95% CI 1.1 to 2.9), and hydrogen sulphide (OR 2.3; 95% CI 1.2 to 4.4) were significant. CONCLUSION: An increased risk of spontaneous abortion was found associated with the exposure to petrochemicals, including benzene, gasoline, and hydrogen sulphide.

Abortion, Spontaneous↗
PubMed1998

Determinants of prognosis in late chronic-phase chronic myelogenous leukemia.

PURPOSE: Since interferon alfa (IFN-A) became an established treatment in chronic myelogenous leukemia (CML), more patients are referred to tertiary centers in late chronic phase (ie, > 12 months after diagnosis). Trials conducted in this phase cannot be evaluated precisely unless the features that determine prognosis in late chronic-phase CML are identified. The purpose of this study is to define the prognostic determinants of late chronic-phase CML. PATIENTS AND METHODS: From 1980 to 1997,257 consecutive CML patients referred in late chronic phase were studied. Their clinical characteristics at the time of referral and their association with survival were investigated. A staging model was designed. RESULTS: The median survival from time of referral was 43 months. Pretreatment characteristics associated with worse outcome included older age, poor performance status, splenomegaly, low albumin level, high percentage of blasts or basophils in peripheral blood (PB) or bone marrow, longer duration of chronic phase, and poor-risk group as defined by the Synthesis model. Prior exposure to IFN-A was not associated with worse outcome. By multivariate analysis, characteristics associated with shorter survival were age of 60 years or older, time from diagnosis of 3 years or greater, performance status of 1 or greater, PB basophils of 7% or greater, spleen 10 cm or greater, PB blasts 3% or greater, and albumin level less than 4 g/dL. A model that included age, duration of chronic phase, performance status, and PB basophils was generated. Patients with no, one, two, or three or greater adverse factors had median survivals of 71, 49, 26, and 19 months, respectively. CONCLUSION: A staging model for late chronic-phase CML can stratify patients in four groups with significantly different outcomes. If confirmed in independent populations, such a model could be considered in the analysis of future trials of treatment strategies in late chronic-phase CML.

Adolescent↗
PubMed1998

Comparison of radiation dose from intravenous urography and 99Tcm DMSA scintigraphy in children.

Intravenous urography (i.v.u.) and 99Tcm DMSA scintigraphy are possible alternative diagnostic techniques in paediatric renal investigation. Radiation dose comparisons between them have been complicated in the past by the lack of paediatric data. In this study, evaluations relevant to children are used to compare estimates of effective dose from the two techniques. For the radiographic procedures, standard operating parameters and representative age-dependent values of entrance surface dose were established from recent literature. Conversion factors relating effective dose to entrance surface dose and dose-area product are presented and used to obtain values of effective dose for single radiographs of abdomen, kidneys and pelvis. Suggested i.v.u. procedures consisting of four ("minimum") or eight ("average") radiographs were adopted to derive the effective dose for full i.v.u. examinations. 99Tcm DMSA dose estimates, taken from our published work using an administered activity schedule based on body surface area, are almost constant at about 1 mSv for all children. In comparison, mean i.v.u. doses based on the "average" number of radiographs are similar to DMSA doses for infants (< 1 year) but may be twice as high for older children. Although the differences between procedures at this level of dose do not in themselves provide grounds for preference, when coupled with the lower diagnostic sensitivity of i.v.u. they suggest limitations of this procedure for detection of a renal scar.

Abdomen↗
PubMed1998

Relationship of blood thromboxane-B2 (TxB2) with lipid peroxides and effect of vitamin E and placebo supplementation on TxB2 and lipid peroxide levels in type 1 diabetic patients.

OBJECTIVE: To study the effect of vitamin E supplementation on platelet hyperaggregability in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: Written informed consent according to the Institutional Review Board on Human Experimentation guidelines was obtained from diabetic patients (n = 29) and their age-matched normal siblings (n = 21) to participate in this study. Diabetic patients were supplemented with DL-alpha-tocopherol (vitamin E) capsule (orally, 100 IU/day) or placebo for 3 months in a double-blind clinical trial. Alternate diabetic patients were assigned to vitamin E or placebo during regular visits to the clinic. Fasting blood was collected from each diabetic patient before the start and after the vitamin E or placebo supplementation. Platelet aggregability was assessed by competitive enzyme-linked immunosorbent assay of the blood TxB2 (a stable thromboxane metabolite). Plasma vitamin E and MDA (malondialdehyde, a product of lipid peroxidation) was assessed by high-performance liquid chromatography. Data were analyzed statistically on 12 diabetic patients on vitamin E and 12 on placebo supplementation. RESULTS: Diabetic patients (n = 29) had 62% higher (P < 0.05) levels of TxB2 and 15% higher levels (P < 0.05) of MDA in comparison to normal subjects (n = 21). Plasma TxB2 levels had a significant correlation with MDA levels (r = 0.45, P < 0.02) but not with the HbA1 (r = -0.08), glucose (r = -0.13), duration of diabetes (r = -0.04), or age (r = 0.12) of diabetic patients. Vitamin E supplementation lowered MDA levels by 30% (P < 0.04), TxB2 levels by 51% (P < 0.03), and triglyceride levels by 22% (P < 0.04) in diabetic patients. There were no differences in these parameters before versus after placebo supplementation. CONCLUSIONS: The elevated blood level of TxB2 (hyperaggregability of platelets) is significantly related to the level of lipid peroxidation products (oxidative stress) in type 1 diabetic patients. Supplementation of modest doses of vitamin E (100 IU/day) significantly lowers blood TxB2 and lipid peroxidation products levels in type 1 diabetic patients.

Child↗
PubMed1998

Incidence of Plasmodium falciparum infection in infants in relation to exposure to sporozoite-infected anophelines.

The relationship of the incidence of Plasmodium falciparum infection to entomologic inoculation rates (EIRs) was studied in 163 children less than one year of age in a Tanzanian village to determine likely effects of transmission-reducing interventions on infection incidence. A total of 66,727 Anopheles gambiae s.l. and 17,620 An. funestus mosquitoes were caught in 1,056 light trap collections from 139 houses over a period of more than two years. Time period-specific human biting rates were estimated for 11 village neighborhoods. Sporozoites were detected by ELISA in 4.4% of the An. funestus and 2.5% of the An. gambiae s.l. Eight hundred seventeen pairs of blood slides with approximately two-week intervals between slides were used to estimate incidence of parasitemia by fitting reversible catalytic models to parasite positivity data. Estimated EIRs during the four weeks preceding each intersurvey interval averaged 1.6 (SD = 2.1) per adult per night. Parasites were present at the end of 31% of the 443 intervals that commenced with a parasite-negative slide. Attack rates were comparable with those in western Kenya, and the proportion of bites resulting in human infections was strongly dependent on mosquito density. Incidence of infection increased with the EIR up to approximately one bite from a sporozoite-carrying mosquito per adult per night. However, higher levels of transmission observed locally in the wet season did not result in a correspondingly higher incidence. These data suggest that transmission-reducing measures cannot be expected to reduce incidence of infection at the highest levels of EIR.

Animals↗
PubMed1998

Relationships of malaria morbidity with exposure to Plasmodium falciparum in young children in a highly endemic area.

To study incidence of clinical Plasmodium falciparum malaria in relation to exposure to parasites, attendance of children less than eighteen months old at a village dispensary in a highly endemic area of Tanzania was recorded. Entomologic inoculation rates (EIRs), estimated as a function of time period and place of residence, exceeded one sporozoite positive bite per adult per night in some village neighborhoods during the wet season. Incidence of clinical P. falciparum malaria, defined either as fever with parasitemia or as fever with hyperparasitemia, increased with the EIR over the whole range of exposures. Each 10-fold increase in the EIR corresponded to a 1.6-fold increase in incidence of fever plus parasitemia (95% confidence interval = 1.4-2.0). Therefore reduction of human-vector contacts will probably reduce morbidity incidence even at very high exposures. Incidence showed little relationship to estimated cumulative numbers of inoculations since birth, but decreased steeply with estimated cumulative time infected with trophozoites. This suggests that clinical immunity depends mainly on the extent of exposure to blood-stage antigens, not on the diversity of inocula seen, and thus temporary reductions in human-vector contacts are unlikely to result in subsequent increases in morbidity.

Animals↗
PubMed1998

Impact of spatial distribution of permethrin-impregnated bed nets on child mortality in rural northern Ghana.

Effects of the distribution in space of permethrin (insecticide)-impregnated bed nets (IIBNS) on child mortality were studied in a randomized controlled trial of IIBNs in a an area highly endemic for Plasmodium falciparum malaria in rural northern Ghana. Eight hundred sixty-two deaths occurred among children 6-59 months of age during 16,841 child-years-at-risk. Mortality increased with the distance from health facilities but not with proximity to identifiable anopheline breeding sites (reservoirs). The efficacy of IIBNs was independent of these distances. Mortality in users of IIBNs was independent of the proximity of nonusers, and mortality rates of nonusers and users living close to each other were similar. Poisson regression estimated a 6.7% increase in mortality among nonusers with each 100-m shift away from the nearest compound with IIBNS, indicating that the insecticide protects nearby nonusers. High coverage of IIBNs achieves maximum impact, but users of IIBNs offer some protection to less fortunate neighbors if coverage is incomplete.

Animals↗