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Biomedical subjects

D Thompson

Publications and source records attributed to D Thompson.

At least 109 records · Page 6Linked to original sources
PubMed1999

Muscular soreness following prolonged intermittent high-intensity shuttle running.

The aim of this study was to examine the impact of prolonged intermittent high-intensity shuttle running on soreness and markers of muscle damage. Sixteen males took part in the study, half of whom were assigned to a running group and half to a resting control group. The exercise protocol involved 90 min of intermittent shuttle running and walking (Loughborough Intermittent Shuttle Test: LIST), reflecting the activity pattern found in multiple-sprint sports such as soccer. Immediately after exercise, there was a significant increase (P < 0.05) in serum activities of creatine kinase and aspartate aminotransferase, and values remained above baseline for 48 h (P < 0.05). Median peak activities of creatine kinase and aspartate aminotransferase occurred 24 h post-exercise and were 774 and 43 U x l(-1), respectively. The intensity of general muscle soreness, and in the specific muscles investigated, was greater than baseline for 72 h after the shuttle test (P < 0.05), peaking 24-48 h post-exercise (P < 0.05). Muscle soreness was not correlated with either creatine kinase or aspartate aminotransferase activity. Soreness was most frequently reported in the hamstrings. Neither soreness nor serum enzyme activity changed in the controls over the 4 day observation period. It appears that unaccustomed performance of prolonged intermittent shuttle running produces a significant increase in both soreness and markers of muscle damage.

Adult↗
PubMed1999

The genetic epidemiology of early-onset epithelial ovarian cancer: a population-based study.

We conducted a population-based study to determine the contribution of germline mutations in known candidate genes to ovarian cancer diagnosed at age <30 years. Women with epithelial ovarian cancer were identified through cancer registries. DNA samples were analyzed for mutations in BRCA1, the "ovarian cancer-cluster region" (nucleotides 3139-7069) of BRCA2, and the mismatch-repair genes hMSH2 and hMLH1. Probable germline mutations in hMLH1 were identified in 2 (2%; 95% confidence interval 1%-8%) of 101 women with invasive ovarian cancer diagnosed at age <30 years. No germline mutations were identified in any of the other genes analyzed. There were no striking pedigrees suggestive of families with either breast/ovarian cancer or hereditary nonpolyposis colorectal cancer (HNPCC). There was a significantly increased incidence of all cancers in first-degree relatives of women with invasive disease (relative risk [RR] = 1.6, P=.01) but not in second-degree relatives or in relatives of women with borderline cases. First-degree relatives of women with invasive disease had increased risks of ovarian cancer (RR = 4.8, P=.03), myeloma (RR = 10, P=.01), and non-Hodgkin lymphoma (RR = 7, P=.004). Germline mutations in BRCA1, BRCA2, msh2, and mlh1 contribute to only a minority of cases of early-onset epithelial ovarian cancer. Our data suggest that early-onset ovarian cancer is not associated with a greatly increased risk of cancer in close relatives.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Management of otitis media among children in a large health insurance plan.

BACKGROUND: Otitis media is one of the most common office diagnoses among children in the US and the leading reason for the use of antimicrobials in pediatric practice. We undertook this study to characterize medical and surgical management of otitis media. METHODS: Using claims data from a large New England health insurer, we identified all children <10 years of age who had one or more episodes of acute otitis media between July, 1995, and June, 1996, and examined patterns of treatment for this condition. RESULTS: Study subjects (n = 22,004) averaged 2.9 physician office visits for management of otitis media; among children <2 years of age, one-fourth had 6 or more such visits. Amoxicillin was prescribed as initial therapy in more than one-half (56.6%) of all episodes of acute otitis media, followed by cephalosporins (18.3%), trimethoprim-sulfamethoxazole (12.3%), macrolides (6.4%) and amoxicillin-clavulanate (6.0%). Over multiple episodes, however, use of amoxicillin declined by about 50%. Antimicrobial prophylaxis was received by 7.3% of all study subjects for a mean of 61.3 days; the incidence of breakthrough episodes of acute otitis media during prophylaxis varied according to the antimicrobial used (13.9, 12.3 and 19.5% for amoxicillin, trimethoprim-sulfamethoxazole and sulfisoxazole, respectively). Surgical procedures related to otitis media were performed on 3.8% of all study subjects, including 4.6% of children <2 years of age. CONCLUSIONS: The health care burden of otitis media is large, particularly in the first 2 years of life.

Acute Disease↗
PubMed1999

Acceptability of a paste formulation and efficacy of high dose omeprazole in healing gastric ulcers in horses maintained in race training.

Gastric ulceration has been found to occur in 80-90% of Thoroughbreds in active race training. Previously, variable success has been reported using mucosal surface protectants and H2 receptor antagonist. Omeprazole, a substituted benzimidazole, has been shown to inhibit gastric acid secretion in both man and animals. Fourteen horses, in active race training and with endoscopic evidence of moderated to severe gastric ulceration were divided into 2 groups: Group 1 (7 horses) were given placebo paste orally once daily for 28 days; Group 2 (7 horses) received 1.54 g active omeprazole in the placebo once daily for 28 days. Logs detailing administration and acceptability of the paste, and the horse's feeding and training regime were maintained by the trainer of each horse. Endoscopic examination of the stomach occurred at the beginning of the trial, and at 13-17 days and 27-31 days following commencement of the trial. Those horses that were free of ulceration on Days 27-31 were reexamined on Days 35-49. Acceptability of the paste, whether with or without active omeprazole, was deemed excellent in all horses except on one occasion, when one horse swallowed the paste following initial mild reluctance. Of the horses given the placebo (Group 1), 3 were withdrawn after the 13-17 day endoscopic examination: 1 horse to be given a H2 receptor antagonist, 1 horse was removed from training due to aryepiglottic entrapment and 1 horse had a greater than 10% fall in bodyweight from the start of the trial. Of the horses given active omeprazole (Group 2), one horses was relocated to another race track following the 13-17 day endoscopic examination. For the horses given placebo (Group 1), there was no change in the severity of ulceration. In contrast, the severity of ulceration in the horses given active omeprazole was significantly reduced at 13-17 days and 27-31 days. In 2 Group 2 horses, ulcers that had been completely eliminated subsequently returned when reexamined at 35-49 days. The results of this study suggest that omeprazole, employing a once daily dosing schedule, is effective at reducing the severity or eliminating gastric ulcers in Thoroughbreds in active race training.

Administration, Oral↗
PubMed1999

CCR5-Mediated human immunodeficiency virus entry depends on an amino-terminal gp120-binding site and on the conformational integrity of all four extracellular domains.

The human immunodeficiency virus type 1 coreceptor activity of CCR5 depends on certain polar and charged residues in its amino-terminal domain. Since studies of chimeric receptors have indicated that the extracellular loops of CCR5 are also involved in viral fusion and entry, we have explored the role of bulky, polar and nonpolar residues in these regions. Selected amino acids in the three extracellular loops were individually changed to alanines, and the coreceptor activities of the mutant CCR5 proteins were tested in a luciferase reporter virus-based entry assay. We found that the cysteines in the extracellular loops of CCR5 are essential for coreceptor activity. However, only minor (two- to threefold) effects on coreceptor function were noted for all of the other alanine substitutions. We also demonstrated that when the first 19 residues of the amino-terminal region were separated from the rest of CCR5, by insertion of glycine/serine spacers between proline 19 and cysteine 20, coreceptor function decreased. Together with our previous studies, these data indicate that both an amino-terminal gp120-binding site and extracellular domain geometry play a role in viral entry.

Amino Acid Substitution↗
PubMed1999

Immunohistochemical expression of pi class glutathione S-transferase in the basal cell layer of benign prostate tissue following chronic treatment with finasteride.

BACKGROUND: Glutathione S-transferases (GST) may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Treatment directed at the induction or preservation of GST-pi expression in normal epithelium could have a profound impact on the prevention of prostate neoplasia. Finasteride, a 5-alpha-reductase inhibitor, is used as a chemopreventive agent because it blocks the conversion of testosterone to its byproduct which promotes prostate tumour growth. OBJECTIVE: To investigate GST-pi expression immunohistochemically in benign prostate tissue from untreated patients and from patients chronically treated with finasteride. MATERIALS: Immunostaining with anti-GST-pi antibody was performed on 10 (cysto-) prostatectomy, eight simple prostatectomy, and three transurethral prostatectomy specimens. The first set of 10 prostates was from untreated patients operated on for bladder cancer. The other cases were from patients with benign prostatic hyperplasia and chronically treated with finasteride. None of the specimens in either group showed prostatic cancer, prostatic intraepithelial neoplasia, urothelial carcinoma, or chronic prostatitis. Specimens were evaluated for the presence, intensity, and distribution of immunostaining. RESULTS: Diffuse cytoplasmic immunostaining was observed in the basal cell layer of the untreated specimens. Some variability in the expression of GST-pi was seen within each zone and also between the prostate zones. Only a minority of the secretory cells was stained weakly, mainly in the subnuclear region of the cells facing an uninterrupted basal cell layer. Staining was more homogeneously diffuse in the cytoplasm of the luminal cells facing the basement membrane directly. In the benign epithelium of the finasteride treated specimens the circumferential staining of the basal cells appeared to be more continuous than in the untreated cases, the gaps in the stained basal cell layer being fewer, shorter, or even absent in some ducts and acini. There was no variability in the intensity of staining of the basal cell layer, all the cells being intensely stained in a uniform way. The intensity of staining of the secretory cells was not influenced by finasteride treatment. CONCLUSIONS: Following chronic treatment with finasteride the immunohistochemical expression of pi class glutathione S-transferase in the benign prostate ducts and acini is upregulated in relation to an expanded basal cell layer. This could indicate that finasteride acts as a GST-pi inducer.

Aged↗
PubMed1999

Subtle morphological and molecular changes in normal-looking epithelium in prostates with prostatic intraepithelial neoplasia or cancer.

BACKGROUND: Prostate cancer develops over an extended period of time. Until recently, the events initiating the process and the developments concomitant with the evolution towards invasive disease were largely unknown. METHODS: Analytical and quantitative methods are applied to provide insights into certain individual molecular events and their effects on the complex multiple feedback system of cellular metabolism and regulation in prostate neoplasia. RESULTS: Prostatic intraepithelial neoplasia (PIN) and prostate cancer (PCa) are associated with or possibly preceded by changes in the chromatin of secretory cell nuclei. The changes are detectable with a Bayesian belief network and quantifiable by computer image analysis in prostatic tissue that still appears histologically normal. In addition, normal-looking prostate epithelium shows some molecular changes similar to those present in the associated preneoplastic and neoplastic lesions. Such changes are also occasionally present in normal prostate glands without PIN and cancer. CONCLUSIONS: The subtle morphological and molecular changes of normal-looking epithelium might be seen as the onset of the development of prostatic neoplasia.

Adenocarcinoma↗
PubMed1999

Tissue architecture analysis in prostate cancer and its precursors: An innovative approach to computerized histometry.

AIMS: It is the aim of these studies to derive a numerically defined progression index for prostatic intraepithelial neoplasia (PIN) lesions. METHODS: Histometric and karyometric features were automatically extracted from images of histopathologic sections by a machine vision system. RESULTS: Both histometric and karyometric measures lend themselves to the defining of a progression index. Karyometric features were found to be more sensitive. They allow the detection of very early change. CONCLUSIONS: It is possible to measure progression of PIN lesions with precision. The methodology would lend itself for measurement of regression due to chemopreventive intervention.

Artificial Intelligence↗
PubMed1999

Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study.

To establish whether biochemical markers could be used to monitor alendronate (ALN) treatment and predict long-term response in bone mass, we used results from an ongoing, randomized trial of ALN treatment for prevention of postmenopausal osteoporosis (n = 1202). In women treated with ALN (5 mg), change from baseline at month 6 in urine N-telopeptide cross-links of type I collagen (NTX) and osteocalcin (OC) correlated with change from baseline at month 24 in spine, hip, and total body bone mineral density (BMD) [r = -0.28 to -0.31 (NTX) and r = -0.16 to -0.25 (OC), P<0.001]. This corresponded to a 4- to 5-fold greater increase at month 24 in BMD in the tertiles, with the greatest decrease at month 6 in NTX or OC. In women treated with ALN (5 mg) who had a change at month 24 in spine BMD of at least 0%, 86% (NTX) and 79% (OC) had a decrease at month 6 of at least 40% (NTX) or 20% (OC) (sensitivity). The corresponding specificities were 48% (NTX) and 53% (OC). In conclusion, change at month 6 in NTX and OC, in groups of women treated with ALN, indicated the numeric long-term response in BMD within these groups. In individual women, a decrease at month 6, in NTX or OC below the cut-point, validly identified women who responded, on ALN treatment, with a stabilization or an increase in bone mass. However, lack of decrease below the cut-point in NTX or OC could not be used to identify women with a bone loss during ALN treatment.

Alendronate↗
PubMed1999

Low body mass index is an important risk factor for low bone mass and increased bone loss in early postmenopausal women. Early Postmenopausal Intervention Cohort (EPIC) study group.

Thinness (low percentage of body fat, low body mass index [BMI], or low body weight) was evaluated as a risk factor for low bone mineral density (BMD) or increased bone loss in a randomized trial of alendronate for prevention of osteoporosis in recently postmenopausal women with normal bone mass (n = 1609). The 2-year data from the placebo group were used (n = 417). Percentage of body fat, BMI, and body weight were correlated with baseline BMD (r = -0. 13 to -0.43, p < 0.01) and 2-year bone loss (r = -0.14 to -0.19, p < 0.01). Women in the lowest tertiles of percentage of body fat or BMI had up to 12% lower BMD at baseline and a more than 2-fold higher 2-year bone loss as compared with women in the highest tertiles (p </= 0.004). Women with a lower percentage of body fat or BMI had higher baseline levels of urine N-telopeptide cross-links (r = -0.24 to -0.31, p < 0.0001) and serum osteocalcin (r = -0.12 to -0.15, p < 0.01). To determine if the magnitude of treatment effect of alendronate was dependent on these risk factors, the group treated with 5 mg of alendronate was included (n = 403). There were no associations between fat mass parameters and response to alendronate treatment, which indicated that risk of low bone mass and increased bone loss caused by thinness could be compensated by alendronate treatment. In conclusion, thinness is an important risk factor for low bone mass and increased bone loss in postmenopausal women. Because the response to alendronate treatment is independent of fat mass parameters, prevention of postmenopausal osteoporosis can be equally achieved in thinner and heavier women.

Alendronate↗
PubMed1999

Lifetime health and economic benefits of weight loss among obese persons.

OBJECTIVES: This study estimated the lifetime health and economic benefits of sustained modest weight loss among obese persons. METHODS: We developed a dynamic model of the relationship between body mass index (BMI) and the risks and costs of 5 obesity-related diseases: hypertension, hypercholesterolemia, type 2 diabetes, coronary heart disease (CHD), and stroke. We then calculated the lifetime health and economic benefits of a sustained 10% reduction in body weight for men and women aged 35 to 64 years with mild, moderate, and severe obesity. RESULTS: Depending on age, gender, and initial BMI, a sustained 10% weight loss would (1) reduce the expected number of years of life with hypertension, hypercholesterolemia, and type 2 diabetes by 1.2 to 2.9, 0.3 to 0.8, and 0.5 to 1.7, respectively; (2) reduce the expected lifetime incidence of CHD and stroke by 12 to 38 cases per 1000 and 1 to 13 cases per 1000, respectively; (3) increase life expectancy by 2 to 7 months; and (4) reduce expected lifetime medical care costs of these 5 diseases by $2200 to $5300. CONCLUSIONS: Sustained modest weight loss among obese persons would yield substantial health and economic benefits.

Adult↗
PubMed1999

Chromatin texture in high grade prostatic intraepithelial neoplasia and early invasive carcinoma.

OBJECTIVE: To evaluate individual nuclei from high grade prostatic intraepithelial neoplasia (PIN) lesions with early invasive carcinoma foci in the area of microinvasion and in the gland in which the microinvasion originated. STUDY DESIGN: High-resolution, digitized images of nuclei from defined locations were recorded and segmented, and karyometric variables were computed. These included a set of 93 features, which form a nuclear signature characterizing the spatial and statistical distribution of the nuclear chromatin. Nuclei in the glandular epithelium were recorded sequentially, along the basal cell layer, at increasing distances from the point of microinvasion and by random selection in the region of microinvasion. RESULTS: At a distance > 60 nuclear locations from the point of microinvasion, the nuclear signatures corresponded to those seen in high grade PIN. Between 40 and 20 nuclear locations removed from the microinvasion focus the signatures began to change gradually until at a distance of 15-5 locations they strongly resembled the signatures seen in adenocarcinoma. The total optical density decreased to values seen in adenocarcinoma, and the nuclear chromatin had finer granularity. While nuclei in high grade PIN followed a widely dispersed total optical density distribution suggestive of wide-ranging aneuploidy, the nuclei in the region of microinvasion exhibited a less dispersed and bimodal total optical density distribution. CONCLUSION: The chromatin texture signatures showed a clear trend: there was an obvious attenuation as the measured nuclei approached the microinvasion area. The decrease in total optical density at the microinvasion might suggest the emergence of one or two clones that can be responsible for the invasive phenotype.

Adenocarcinoma↗
PubMed1999

Distinguishing cortical adrenal gland adenomas from carcinomas by their quantitative nuclear features.

OBJECTIVE: To explore data from a set of cases of adrenal cortical adenomas with different endocrine syndromes and carcinomas to determine whether quantitative image analysis of nuclear features might be used to separate the groups. STUDY DESIGN: Fifteen adrenal cortical tumors in which clinical information and optimally preserved, paraffin-embedded tissue were available were used. There were 10 adenomas and 5 carcinomas. Among the adenomas, five were associated with primary hyperaldosteronism (Conn's syndrome) and five with Cushing's syndrome. Five-micrometer-thick sections were stained with hematoxylin and eosin. In each case 50 nuclei were measured, and a number of morphometric and densitometric features were extracted. The data were subjected to multivariate analysis. RESULTS: Quantitative analysis showed that nuclei from adrenal carcinomas are larger than those from adenomas. Total optical density (OD) had a near-diploid distribution in the adenomas, while it was clearly aneuploid in the carcinomas. The pixel OD histograms were almost identical for all groups. Differences in nuclear chromatin texture were found between adenomas and carcinomas and also between the two adenoma categories. Multivariate analysis showed good discrimination between carcinomas and adenomas (Wilks lambda = .628, P < .0001) and between adenomas. However, based on Bayesian decision boundaries, 20-25% of carcinoma nuclei could be expected to be in the range of adenoma, and about 12% of Cushing's adenoma nuclei and 15% of Conn's adenoma nuclei would be classified as carcinoma. CONCLUSION: Computer-assisted analysis of nuclear characteristics proved useful in identifying and describing differences between groups of tumors arising in the adrenal cortex.

Adenoma↗
PubMed1999

Case-based prediction of survival in colorectal cancer patients.

OBJECTIVE: To develop an approach to the prediction of survival in patients with colorectal cancer using nearest neighbor analysis and case-based reasoning. STUDY DESIGN: A total of 216 patients with full clinicopathologic records and five-year follow-up were the subjects of this study. They were divided into a core database of 162 cases and a test group of 54 cases, with follow-up on all patients. When the patient was still alive at the end of the follow-up period, censored survival time was used. For each of the test cases, the four closest neighbors from the database were retrieved and their median survival time recorded and used as the predicted estimate of survival. Case matching was based on a Euclidean multivariate distance measure for the three best predictor variables: patient age, Dukes stage and tubule configuration. Cases with the smallest distance from the test case were considered to be the most similar. The predicted survival times for the test cases were compared with the actual, observed survival in the test cases to determine the success of this approach. RESULTS: The results showed reasonable concordance between observed and predicted survival figures, although there was a large degree of spread. Classification of cases into < or = 60 and > 60 months' survival showed a correct classification rate of 63%. For the prediction of survival time, the distribution of differences between observed and predicted survival times for the uncensored test cases had a median value of--5 months but also showed a wide dispersion of values. Correlation of observed and predicted survival times, while not reaching statistical significance at P < .05, did show a strong positive association. CONCLUSION: Case-based approaches to the prediction of survival times in cancer patients are important. The results of the current study illustrate the difficulties in applying this approach to survival data and highlight the complexity of patient information and the inability to accurately predict patient outcome on a small subset of clinicopathologic features. While extensive work needs to be carried out to improve prediction power, this study illustrates the potential for case-based analyses. The ability to retrieve feature-matched cases from hospital patient databases has clear, independent advantages in patient management, but the ability to provide reliable, targeted prognostic estimates on individual cases should be a common goal in medical research.

Adult↗
PubMed1999

The prevention of playground injuries.

Playground accidents are the most common cause of injury to children in school. As the health professional who attends to these injured children, school nurses should be aware of safety practices that can help eliminate the risks that children encounter. The National Program for Playground Safety has identified four areas that can reduce the level of risk on school playgrounds: supervision, age-appropriate design of the play area, fall surfaces under and around playground equipment, and equipment and surface maintenance. The article discusses each of these, and recommends leadership methods and practices that nurses can implement that will eliminate or reduce risk factors. In addition, a comprehensive playground risk model is described, and suggestions for policy areas are outlined. Policy areas include assessment, education, and enforcement in relation to each of the risk factors.

Accidental Falls↗