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Biomedical subjects

W D Thompson

Publications and source records attributed to W D Thompson.

At least 37 records · Page 2Linked to original sources

Fibrin gel induces the migration of smooth muscle cells from rabbit aortic explants.

A major step in the pathogenesis of atherosclerosis is the vectorial migration of smooth muscle cells (SMCs) from the arterial media into the intima. Although subcultured SMCs usually show synthetic phenotype, the behaviour of contractile SMCs may be crucial for the subsequent migration of the cells. In the present study, we utilized an in vitro assay system to evaluate the effects of fibrin gels on the migration of SMCs from explants taken from rabbit aorta. After cultured for 5-7 days in a serum-free condition, SMCs appeared from explants covered with fibrin gel. The cells were positive on immunostaining for SMC specific alpha-actin. No migration of SMCs from the control explants without fibrin gel was observed. Then the percentage of explants showing cell migration and the number of migrating cells increased with time. The migration of SMCs into fibrin gels was not dependent on the concentration of fibrinogen used for the preparation of fibrin gel in the range of 1.5-3 mg/ml. Variations of thrombin concentration in the range of 0.25-1.25 U/ml had no significant effect. However, there was less migration of SMCs with higher concentrations of thrombin. Thrombin inhibitors, hirudin and PPACK had no significant effect on the migration of SMCs. An RGD-containing peptide, GRGDS inhibited the migration of SMCs although a control peptide GRGES at the same concentration had no significant effect. A monoclonal antibody to alphavbeta3, LM609, completely inhibited the migration of SMCs from the explants, suggesting that alphavbeta3 integrin is involved in the migration of SMCs into fibrin gels. SMCs which migrated from the explants showed the positive staining with the monoclonal antibodies against SMC myosin heavy chain isoforms, SMemb, SM1 and SM2, suggesting that they are in an intermediate state changing from contractile to synthetic state. In conclusion, the present study showed that fibrin gel induces the migration of SMCs from explants into itself and the process may not need other growth factors or cytokines.

Animals↗

Effect of crosslinking by factor XIIIa on the migration of vascular smooth muscle cells into fibrin gels.

We evaluated the migration of vascular smooth muscle cells into crosslinked fibrin gels, using an in vitro assay system. Vascular smooth muscle cells from bovine fetal aorta migrated into non-crosslinked and crosslinked fibrin gels and showed a characteristic elongated spindle-shaped appearance with long cytoplasmic processes. The cells displayed two-fold increase in migration into crosslinked fibrin gels compared to non-crosslinked gels, suggesting the importance of fibrin crosslinking by factor XIIIa on its three-dimensional structure for the migration of smooth muscle cells.

Animals↗

Differential misclassification and the assessment of gene-environment interactions in case-control studies.

In case-control studies of interactions between genetic and environmental exposures, differential misclassification of the environmental exposure with respect to disease status can introduce spurious heterogeneity of the stratum-specific odds ratios. In this paper, the authors identify conditions under which differential misclassification does not introduce bias in the interaction parameter when no multiplicative interaction is present, and it biases the interaction parameter toward the null value when a multiplicative interaction is present. The conditions are that (i) conditional on potential confounders, the environmental exposure is independent of the genotype among the controls, and (ii) misclassification of the environmental exposure is nondifferential with respect to the genotype. These conditions can be tested from the misclassified data in the control group, since a test of the independence of the genotype and the misclassified environmental exposure among the controls is a test of the joint hypothesis that conditions (i) and (ii) are both true. Therefore, the authors propose a two-step test for interaction which first tests conditions (i) and (ii) and then goes on to test for interaction, provided the first step hypothesis is not rejected. A summary test procedure to test for gene-environment interactions in the presence of misclassification, based on both a conventional test for interaction and the two-step test, is recommended, and is illustrated with data from a case-control study of the role of diet as a modifier of the association between a metabolic polymorphism and lung cancer.

Case-Control Studies↗

Utilization patterns of cord blood gas analysis.

OBJECTIVE: To determine patterns of use of cord blood gas analysis in two institutions in Portland, Maine; to determine which factors, if any, predicted use of the test; and to evaluate compliance with ACOG guidelines. METHODS: Billing data were used from 3166 deliveries during 1994 in the two hospitals to find deliveries in which the test was performed. We merged billing data with birth certificate data to examine factors associated with the test's use. Finally, we compared its use in our community with recently updated ACOG guidelines. RESULTS: There was a 20-fold difference in the test's use between institutions (P < .001). The test was performed in 49% of all births at the tertiary care center and 2.5% of births at the community hospital. Many maternal and neonatal factors were linked to use of the test, but delivery system factors, in particular, the institution, were the strongest predictors of the test's use, even controlling for confounding factors between hospitals. There was little adherence to ACOG guidelines, with 97% of the tests being performed in situations in which ACOG's recommendations did not support use of the analysis. CONCLUSION: Current use of cord blood gas analysis in our community is not consistent with guidelines or cost-effective use of resources; the institutional factors that determine excess use should be examined and modified.

Blood Gas Analysis↗

CHOP-based chemotherapy is as effective as alternating PEEC/CHOP chemotherapy in a randomised trial in high-grade non-Hodgkin's lymphoma. Scotland and Newcastle Lymphoma Group.

The aim of this study was to test whether survival for patients with high-grade non-Hodgkin's lymphoma (NHL) can be improved with a non-cross-resistant regimen as compared to a CHOP-based regimen. This is a multicentre study comprising 325 adult patients, median age 58 years, with high-grade non-Hodgkin's lymphoma: patients of any age and performance status were eligible provided they were able to receive the drugs in the regimens. Patients were randomised to either B-CHOP-M (bleomycin, cyclophosphamide, doxorubicin, vincristine, prednisolone and methotrexate) or PEEC-M (methylprednisolone, vindesine, etoposide, chlorambucil and methotrexate) alternating with B-CHOP-M. At a median follow-up of 9 years, there was no significant difference in overall survival or disease-free survival between the two arms. Toxicities for the two regimens were equivalent. This study confirms that for relatively unselected patients with high-grade non-Hodgkin's lymphoma, an alternating multidrug regimen does not improve upon the results obtained with B-CHOP-M.

Adult↗

Diet and premenopausal bilateral breast cancer: a case-control study.

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.

Adult↗

Inducible nitric oxide synthase demonstrated in allergic and irritant contact dermatitis.

Eight allergic patch test reactions, eight irritant skin reactions induced by 3% sodium lauryl sulphate and six normal controls were biopsied. Biopsies were immunohistochemically stained with a mouse monoclonal antibody to inducible nitric oxide synthase (iNOS), and staining was quantified by computerised image analysis. Human chondrocytes induced to express iNOS were used as a positive control. A significant increase in iNOS was found in both irritant and allergic contact dermatitis. There were no differences in the distribution of expression of iNOS. The antibody used was confirmed by Western blotting not to cross-react with the endothelial isoform of nitric oxide synthase (NOS) but did cross-react with a 150 kDa protein, which may be neuronal NOS or an isoform of neuronal NOS.

Adult↗

The genetic attributable risk of breast and ovarian cancer.

BACKGROUND: The age-specific proportion of breast and ovarian cancer in the general population that is likely to be due to a breast/ovarian cancer susceptibility gene(s) is estimated. In addition, the age-specific penetrance of ovarian cancer for women predicted to be carriers of a susceptibility gene is calculated using population-based data. METHODS: Data are from the Cancer and Steroid Hormone Study, a population-based, case-control study conducted by the Centers for Disease Control, which includes 4730 breast cancer cases aged 20 to 54 years. Information regarding the occurrence of breast and ovarian cancer was collected for mothers and sisters of the cases during an in-home interview. The probability of being a breast cancer susceptibility gene carrier was calculated for each of the breast cancer cases using information on the family history of breast cancer. The calculated risk of ovarian cancer in the first-degree relatives of breast cancer cases with a high probability of being a gene carrier is compared with that seen in first-degree relatives of breast cancer cases with a low probability of being a gene carrier and used to calculate the proportion of ovarian cancer cases that are likely to be due to a breast/ovarian susceptibility gene(s) as well as the age-specific risk of developing ovarian cancer for gene carriers. RESULTS: Approximately 10% of ovarian cancer cases and 7% of breast cancer cases in the general population are estimated to be carriers of a breast/ovarian cancer susceptibility gene; these women are found primarily in families characterized by multiple cases of the early onset of breast cancer. The proportion of breast cancer cases predicted to be attributable to the gene decreases markedly with age; approximately 33% of cases age 20-29 years compared with approximately 2% of cases age 70-79 years. The proportion of ovarian cancer cases predicted to be due to the susceptibility gene ranges from 14% among patients diagnosed in their 30s to 7% among those diagnosed in their 50s. Carriers are predicted to have at least 15 times the age-specific risk of ovarian cancer of noncarriers. Among women predicted to carry the gene, the cumulative risk of developing ovarian cancer by the age of 59 years is approximately 10%. CONCLUSIONS: The estimates provided may prove helpful to clinicians until such time as large-scale population-based screening for breast and ovarian cancer susceptibility genes is possible.

Adult↗

Tubal sterilization and the risk of endometrial cancer.

Several animal and human studies suggest that tubal occlusion may curtail ovarian function, altering the production and balance of endogenous estrogens and progesterone, 2 hormones closely related to endometrial carcinogenesis. Despite this, and the increasing world-wide popularity of this method of contraception, little is known about its relationship with the risk of developing endometrial cancer. To assess whether tubal sterilization influences a woman's risk of developing epithelial endometrial carcinoma, data from a large multicenter population-based case-control study of endometrial cancer were analyzed. Cases were 437 women aged 20 to 54 years with histologically confirmed epithelial endometrial cancer ascertained through 6 population-based cancer registries in the United States. Controls were 3200 women selected at random from the populations of the areas from which the cases were detected. As compared with women who had never had tubal sterilization, women who had had this surgery had a crude odds ratio of 0.58 [95% confidence interval (CI), 0.43-0.78]. However, after adjusting for the combined confounding effects of age and parity, the magnitude of the protective association decreased to 0.87 (95% CI, 0.63-1.20). The magnitude of the protective effect did not significantly change with years since surgery or age at surgery. Although a modest, non-significant protective effect is suggested, these findings indicate that tubal sterilization does not substantially alter the risk of developing epithelial endometrial cancer in women 20 to 54 years of age. If there is an increase in risk, these data indicate that it is unlikely to be any greater than 20%.

Adult↗

Exogenous sex hormone use, correlates of endogenous hormone levels, and the incidence of histologic types of sarcoma of the uterus.

BACKGROUND: We analyzed data from a population-based, multi-center, case-control study to determine whether the occurrence of histologic types of uterine sarcoma is related to exogenous hormone use and/or to two correlates of endogenous estrogens: excess weight and cigarette smoking. METHODS: One hundred sixty-seven women with newly-diagnosed uterine sarcoma (56 leiomyosarcoma, 85 mixed mullerian tumors, and 26 endometrial stromal sarcomas) were interviewed by telephone regarding possible risk factors for these neoplasms, For comparison, 208 women identified at random from the general population of the study areas were interviewed as controls. RESULTS: Use of oral contraceptives was positively associated with the risk of leiomyosarcoma (odds ratios [OR] = 1.7, 95% confidence interval [CI] = 0.7, 4.1), primarily among women who last used these medications 15 or more years prior to diagnosis. Use of noncontraceptive estrogens was directly associated with the risk of mixed mullerian tumors, but only among recent and long-term users of these medications. Women in the highest quantile of body mass index (> or = 27.5 kg/m2) one year prior to diagnosis were at increased risk of each type of uterine sarcoma (leiomyosarcoma, OR = 2.5, 95% CI = 1.1, 5.7; mixed mullerian tumors, OR = 2.9, 95% CI = 1.3, 6.7; stromal sarcoma, OR = 3.5, 95% CI = 1.1, 10.9). Women who had ever smoked cigarettes were at reduced risk of leiomyosarcoma (OR = 0.6, 95% CI = 0.3, 1.1) and stromal sarcoma (OR = 0.5, 95% CI = 0.2, 1.2), but the relationship was not more pronounced among heavy smokers; no association with smoking was observed with mixed mullerian tumors. CONCLUSIONS: Several of these findings parallel those from studies of endometrial carcinoma and may indicate a role for unopposed estrogen in the etiology of histologic types of uterine sarcoma.

Adolescent↗

The use and interpretation of the Friedman test in the analysis of ordinal-scale data in repeated measures designs.

The purpose of this paper is to review the use and interpretation of the Friedman two-way analysis of variance by ranks test for ordinal-level data in repeated measurement designs. Physical therapists frequently make three or more repeated measurements of the same individual to compare different treatments, or to assess the effect of a single treatment over time. When the measurements are ordinal-scaled, such as some ratings of functional status and muscle strength, statistical significance may be determined by the Friedman test. We illustrate the use of the Friedman test and a post hoc multiple comparison test with data from 27 subjects whose performance on a lifting task was rated on three occasions by use of an ordinal scale. We discuss the interpretation of ordinal-level data and recommend that therapists understand the limitations a measurement scale imposes on the inferences that can be made from these tests.

Analysis of Variance↗

A population-based study of endometrial cancer and familial risk in younger women. Cancer and Steroid Hormone Study Group.

Endometrial cancer remains an important cause of morbidity and mortality in the United States, and recent genetic evidence supports the hypothesis that hormonal dysregulation is not the only important risk factor for this tumor. This multicenter, population-based case-control study investigated familial aggregation of endometrial cancer and other cancers. Cases were 455 women 20-54 years of age diagnosed with histologically confirmed primary epithelial carcinoma of the endometrium. Controls consisted of 3216 women 20-54 years of age identified by random-digit dialing. Family histories of cancer in female relatives were obtained by interview of cases and controls. Endometrial cancer in a first-degree female relative increased the risk of endometrial cancer by nearly 3-fold [odds ratio (OR), 2.8; 95% confidence interval (CI), 1.9-4.2]. Cases also reported significantly more colorectal cancer in family members than did controls (OR, 1.9; 95% CI, 1.1-3.3). Family history of cancer of the cervix, lung, ovary, and thyroid was not significantly associated with endometrial cancer, and breast cancer was not related unless more than one relative was affected. Family history of endometrial cancer is an independent risk factor for cancer of the endometrium. In addition, the observed association with a family history of colorectal cancer suggests that genes important in familial colorectal cancer may have substantial implications for endometrial cancer. Nearly 5% of incident endometrial cancer among women between the ages of 20 and 54 may be attributable to a family history of endometrial cancer, and 2% may be related to colorectal cancer.

Adult↗