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T C Smith

Publications and source records attributed to T C Smith.

At least 37 records · Page 2Linked to original sources
PubMed1998

Gulf War Veterans' Health Registries. Who is most likely to seek evaluation?

Since the Persian Gulf War ended in 1991, many veterans have sought medical evaluation in the Department of Veterans Affairs Persian Gulf Veterans' Health Registry (VA registry) or the Department of Defense's Comprehensive Clinical Evaluation Program (DoD registry). Using combined data collected from 1993 to 1997 from the VA and DoD registries, the authors compared the characteristics of registry participants (n=74,653) with those of all Gulf War veterans (n=696,531) to determine the personnel most likely to seek medical evaluation. Using multiple logistic regression, the authors found that service branch and type were strongly associated with registry participation, with Army (adjusted odds ratio (OR)=4.7, 95% confidence interval (CI) 4.6-4.9) and National Guard (OR=2.6, 95% CI 2.5-2.6) personnel at highest odds compared with reference category personnel. Registry participants also were more likely to have been stationed in the Gulf War theater during the fighting (OR=2.2), to be older (>31 years/<22 years OR=2.1), to have been an enlisted person (OR=2.0), to have been construction workers (OR=1.3), to be female (OR=1.3), and to have been hospitalized during the 12-month period before the war (OR=1.2). These findings are useful in generating hypotheses regarding postwar morbidity. They also suggest that subpopulations of Gulf War veterans have a higher prevalence of symptoms and merit further study.

Adult↗
PubMed1997

Investigating underlying risk as a source of heterogeneity in meta-analysis.

In a meta-analysis of clinical trials, an important issue is whether the treatment benefit varies according to the underlying risk of the patients in the different trials. The usual naive analyses employed to investigate this question use either the observed risk of events in the control groups, or the average risk in the control and treatment groups, as a measure of underlying risk. These analyses are flawed and can produce seriously misleading results. We show how their biases depend on three components of variability, the within-trial and between-trial variances of the control group risks, and the between-trial variance of the treatment effects. We propose a Bayesian solution to the problem which can be carried out using the BUGS implementation of Gibbs sampling. The analysis is illustrated for a meta-analysis of bleeding and mortality data in trials of sclerotherapy for patients with cirrhosis, and the results contrasted with those from the naive approaches. Comparisons with other methods recently proposed for this problem are also made. We conclude that the Bayesian solution presented in this paper is not only more appropriate than other proposed methods, but is also sufficiently easy to implement that it can be used by applied researchers undertaking meta-analyses.

Bayes Theorem↗
PubMed1997

The Gothenburg breast screening trial: first results on mortality, incidence, and mode of detection for women ages 39-49 years at randomization.

BACKGROUND: The effect of mammography screening on breast carcinoma mortality in women ages < 50 years remains unclear. METHODS: A randomized trial of invitation to breast carcinoma screening with mammography was performed in the city of Gothenburg, Sweden. The purpose was to estimate the effect of mammographic screening on breast carcinoma mortality in women ages < 50 years. Randomization was initially by day-of-birth cluster (18% of subjects), and subsequently by individual (82% of subjects). Between September 1983 and April 1984, 11,724 women ages 39-49 years were randomized to the study group. This group was invited to mammographic screening every 18 months. Two-view mammography was used at each screen unless the density of the breast at the previous screen indicated that single view was adequate. Fourteen thousand two hundred and seventeen women in the same age range were randomized to a control group that was not invited to undergo screening until the fifth screen of the study group (between 6 and 7 years after randomization). Women with breast carcinoma diagnosed up to the time immediately after the first screen of the control group were followed for death from breast carcinoma until the end of December 1994. RESULTS: A 45% reduction in mortality from breast carcinoma was observed in the study group compared with the control group (relative risk [RR] = 0.55, P = 0.035, 95% confidence interval [CI], 0.31-0.96). A conservative estimate based on removal of the tumors detected at the first screen of the control group gave a mortality reduction of 44% (RR = 0.56, P = 0.046, 95% CI, 0.31-0.99). In both cases, the effect was statistically significant. CONCLUSIONS: Mammographic screening can reduce mortality from breast carcinoma in women ages < 50 years. The mortality reduction can be substantial if high quality mammography is used and an 18-month interscreening interval is strictly adhered to.

Adult↗
PubMed1997

Colorectal cancer mass-screening: estimation of faecal occult blood test sensitivity, taking into account cancer mean sojourn time.

Mass screening using the faecal occult blood test (FOBT) can reduce mortality from colorectal cancer. Reliable estimation of FOBT sensitivity is crucial in assessing the potential effectiveness of a mass-screening procedure. Available estimates could be inaccurate because they neglect the temporal aspect of screening. The aim of our study was to estimate the sensitivity of the FOBT in mass screening for colorectal cancer, taking into account the duration of the pre-clinical phase of the disease assessed by the mean sojourn time (MST), and to assess whether MST and FOBT sensitivity differ according to cancer subsite. We analysed data taken from the first round of the mass-screening programme of the department of Calvados (France), involving 164,364 subjects of whom 43.4% participated in FOB screening. MST and sensitivity were estimated using a simple empirical approach, a traditional maximum likelihood method and log-linear modelling using the Bayesian technique of Gibbs sampling. MST was estimated as between 4.5 and 5 years for all subsites combined. According to the Gibbs sampling method, MSTs were 3.5, 6.4 and 2.6 years for proximal colon, distal colon and rectal cancer, respectively. Our estimation methods give a low sensitivity for the FOBT (50%), results for different subsites being closer to each other, slightly higher for proximal cancer. Our results strongly suggest that tumour growth rates are very different according to subsite, slowest for distal cancer and speediest for rectal cancer. Consideration of FOBT sensitivity without MST appears unreliable. Our results by subsite suggest that combining FOBT and sigmoidoscopy could be a good strategy for colorectal cancer screening.

Aged↗
PubMed1997

Regulation by insulin of a unique neuronal Ca2+ pool and of neuropeptide secretion.

The insulin receptor is a tyrosine kinase receptor that is found in mammalian brain and at high concentrations in the bag cell neurons of Aplysia. We show here that insulin causes an acute rise in intracellular Ca2+ concentration ([Ca2+]i) in these neurons and triggers release of neuropeptide. The insulin-sensitive intracellular Ca2+ pool differs pharmacologically from previously described Ca2+ stores that are sensitive to inositol trisphosphate and from mitochondrial Ca2+ stores. Insulin, but not thapsigargin, stimulates Ca2+ release at the distal tips of neurites, the presumed site of neuropeptide secretion. The effects of insulin on intracellular Ca2+ release and neuropeptide secretion occur without triggering spontaneous action potentials. The insulin-sensitive rise in [Ca2+]i moves into the distal tips of neurites after exposure to a cyclic AMP analogue, a treatment that causes a similar translocation of neuronal vesicles. Our data indicate that Ca2+ release from a distinct intracellular pool associated with secretory vesicles may contribute to secretion of neuropeptide in the absence of neuronal discharge.

Animals↗
PubMed1997

Effects of age and food restriction on calcium signaling in parotid acinar cells of Fischer 344 rats.

In this study, we characterized alpha-adrenergic (alpha AR) and muscarinic induced [Ca2+]i changes in individual parotid acinar cells from male Fischer 344 rats (6-24 month-old) fed ad libitum (AL) or 60% ad libitum intake (FR). Cells were prepared by collagenase/hyaluronidase digestion. [Ca2+]i was measured by video image, fluorescent microscopy in single acinar cells loaded with FURA2. Neither age nor food restriction altered the peak [Ca2+]i achieved in response to carbachol (100 microM). Similar results were obtained for epinephrine (Epi = 100 microM) stimulation in 6- and 12-month-old animals. However, the peak [Ca2+]i response to Epi declined between 12 and 18 months in both dietary groups (e.g., AL: 12 months = 387 +/- 21 nM, 18 months = 253 +/- 10 nM; FR: 12 months = 430 +/- 22 nM, 18 months = 325 +/- 14 nM). The decline in response to Epi seen with age was less in FR than in AL animals at 18 months, but not at 24 months. In addition, db cAMP reduced the carbachol-stimulated [Ca2+]i response to levels comparable to those observed with epinephrine. The results support the view that calcium mobilization in parotid acinar cells from male Fischer 344 rats in response to alpha AR, but not to muscarinic, stimulation is impaired with age. Food restriction may slow down, but does not prevent, the functional decline. Furthermore, cAMP appears to modulate the muscarinic response.

Aging↗
PubMed1997

Recent results from the Swedish Two-County Trial: the effects of age, histologic type, and mode of detection on the efficacy of breast cancer screening.

The effect of mammographic screening in reducing mortality from breast cancer is known to be smaller and more delayed in women aged 40-49 than in women over 50. In this study, we investigated how these phenomena relate to histology-specific breast cancer incidence and mortality. The data are from 2,468 women with breast cancer who participated in the Swedish Two-County Trial. The overall relative breast cancer mortality of invited to noninvited women aged 40-49 was 0.87, and the relative mortality from poorly differentiated (grade 3) ductal carcinoma was 0.95. These results were not statistically significant. The corresponding relative risks for invited women aged 50-74 were a statistically significant 0.65 and 0.61. We conclude that in this trial, with a two-year interscreening interval, the smaller and later effect of invitation to screening on breast cancer mortality in women 40-49 years old is due to the failure of screening to reduce mortality from grade 3 ductal carcinoma in this age group.

Adult↗
PubMed1997

The Gothenburg Breast Cancer Screening Trial: preliminary results on breast cancer mortality for women aged 39-49.

We carried out a randomized trial of invitation to screening mammography in the city of Gothenburg, Sweden, to estimate the effect of screening on breast cancer mortality in women under age 50 years. A total of 11,724 women aged 39-49 were randomized to the study group, which was invited to mammographic screening every 18 months; 14,217 women in the same age range were randomized to a control group, which was not invited to screening until the fifth screen of the study group. Breast cancers diagnosed in both groups between randomization and immediately after the first screen of the control group were followed up for death from breast cancer to the end of December 1994. There was a significant 44% reduction in mortality from breast cancer in the study group compared to the control group (relative risk [RR] = 0.56, P = 0.042, 95% confidence interval [CI]: 0.32-0.98). A conservative estimate based on removal of the cancers detected at the first screen of the control group gave an RR = 0.59 (P = 0.069, 95% CI: 0.33-1.05). The true answer is likely to lie between the two estimates. These data suggest that mammographic screening can reduce breast cancer mortality in women under age 50, particularly if high-quality mammography is used and a short interscreening interval is adhered to.

Adult↗
PubMed1997

Markov models of breast tumor progression: some age-specific results.

Researchers have noted that mammographic screening has a reduced effect on breast cancer mortality in women in their forties compared to older women. Explanations for this include poorer sensitivity in younger women due to denser breast tissue, as well as more rapid tumor progression, giving a shorter mean sojourn time (the average duration of the preclinical screen-detectable period). To test these hypotheses, we developed a series of Markov-chain models to estimate tumor progression rates and sensitivity. Parameters were estimated using tumor data from the Swedish two-county trial of mammographic screening for breast cancer. The mean sojourn time was shorter in women aged 40-49 compared to women aged 50-59 and 60-69 (2.44, 3.70, and 4.17 years, respectively). Sensitivity was lower in the 40-49 age group compared to the two older groups (83%, 100%, and 100%, respectively). Thus, both rapid progression and poorer sensitivity are associated with the 40-49 age group. We also modeled tumor size, node status, and malignancy grade together with subsequent breast cancer mortality and found that, to achieve a reduction in mortality commensurate with that in women over 50, the interscreening interval for women in their forties should be less than two years. We conclude that Markov models and the use of tumor size, node status, and malignancy grade as surrogates for mortality can be useful in design and analysis of future studies of breast cancer screening.

Adult↗
PubMed1997

A review of stress ulcer prophylaxis in the neurosurgical intensive care unit.

STRESS ULCERS OCCUR frequently in intensive care unit patients who have intracranial disease. After major physiological stress, endoscopic evidence of mucosal lesions of the gastrointestinal tract appears within 24 hours of injury; 17% of these erosions progress to clinically significant bleeding. Gastrointestinal hemorrhage has been associated with mortality rates of up to 50%. The pathogenesis of stress ulcers may not be completely understood, but gastric acid and pepsin appear to play significant roles. Antacids, H2 antagonists, and sucralfate are effective prophylactic agents in the medical/surgical intensive care unit. Appropriate therapy for neurosurgical patients remains unclear, however. This review summarizes the current literature regarding the pathogenesis and therapy of stress ulcers in neurosurgical patients.

Animals↗
PubMed1996

Subcellular mechanisms of angiotensin II and arginine vasopressin activation of area postrema neurons.

Angiotensin II (ANG II) and arginine vasopressin (AVP) act on area postrema (AP) neurons to modulate the baroreflex. Because activation of AP neurons by either ANG II or AVP increases intracellular free Ca2+ concentrations ([Ca2+]i), the goal of this study was to analyze the factors affecting the [Ca2+]i responses to ANG II and AVP. Neurons were recovered from 14- to 16-day old rats and studied after 8-14 days in culture by use of the microscopic digital image analysis for fura 2-loaded cells. The effects of ANG II (100 nM) and AVP (100 nM) on [Ca2+]i were determined in normal (2 mM) and low (< 10 nM) extracellular Ca2+ concentrations. In 143 of 240 neurons, ANG II increased [Ca2+]i 4.65-fold after 20 s, and a similar response was observed in the absence of extracellular Ca2+ (3.65-fold after 20 s). After 60 s of observation, steady-state levels of increased [Ca2+]i were still present under both conditions. Pretreatment with AT1 antagonist or pertussis toxin abolished the response to ANG II. AVP also increased [Ca2+]i (3.6-fold at peak, 20 s) in normal and low extracellular Ca2+. Pretreatment with AVP V1 antagonist or pertussis toxin abolished the response to AVP. This study indicates that ANG II-induced increases in [Ca2+]i are independent of extracellular Ca2+ concentrations and involve the activation of AT1 receptors and a pertussis toxin-sensitive G protein. Although AVP affects a fewer number of AP neurons, the mechanisms of activation are also independent of extracellular Ca2+ concentration and are mediated by a pertussis toxin-sensitive G protein.

Angiotensin II↗
PubMed1995

Bayesian approaches to random-effects meta-analysis: a comparative study.

Current methods for meta-analysis still leave a number of unresolved issues, such as the choice between fixed- and random-effects models, the choice of population distribution in a random-effects analysis, the treatment of small studies and extreme results, and incorporation of study-specific covariates. We describe how a full Bayesian analysis can deal with these and other issues in a natural way, illustrated by a recent published example that displays a number of problems. Such analyses are now generally available using the BUGS implementation of Markov chain Monte Carlo numerical integration techniques. Appropriate proper prior distributions are derived, and sensitivity analysis to a variety of prior assumptions carried out. Current methods are briefly summarized and compared to the full Bayes analysis.

Bayes Theorem↗
PubMed1994

Recognition of cardiogenic artifact in pediatric capnograms.

The capnograph is in regular use as a respiratory monitor. From measurements of its trace, calculations of breathing rate and end-tidal carbon dioxide can be made. Unfortunately, the reliability of these calculations depends on the quality of the signal. In the case of cardiogenic oscillations, the averaged results may be grossly inaccurate and, therefore, misleading. This paper describes a method for detecting such cardiogenic oscillations and removing their effect from the final results of capnogram analysis. The algorithm used resulted in a sensitivity of 99.6% and a specificity of 99.2%, when compared with manual scoring. The criteria could easily be incorporated into equipment software and are a step in the direction of "intelligent" monitoring.

Algorithms↗
PubMed1994

Relapse rates in patients treated with dapsone monotherapy and combinations of dapsone and thiambutosine, thiacetazone, isoniazid and streptomycin in the pre-MDT era.

Relapse rates were studied in patients from northern Thailand who were started on dapsone monotherapy between 1949 and 1976. Included are a group of patients who, for various reasons, also received combinations of dapsone and thiambutosine, thiacetazone, isoniazid and streptomycin. The overall relapse rate in paucibacillary patients on dapsone monotherapy only was 2.7 per 1000 person-years at risk (PYR) (average observation period 13.9 years). In the multibacillary patients who received dapsone monotherapy only, the relapse rate was 10.5 per 1000 PYR (average observation period 12.4 years). In both groups it was found that 50% of the relapses occurred after the seventh year of follow up. The overall relapse rate in those patients whose treatment included thiambutosine, thiacetazone, isoniazid and/or streptomycin for at least 3 months was 17.9 per 1000 PYR (average observation period 11.9 years). The difference with the multibacillary patients treated with dapsone monotherapy only is not significant. It is concluded that alternative antileprosy drugs included in therapy regimens with dapsone in the pre-MDT era did not result in relapses occurring less often.

Dapsone↗