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Biomedical subjects

B Ward

Publications and source records attributed to B Ward.

At least 37 records · Page 2Linked to original sources
PubMed2000

Oxychlordane and trans-nonachlor in breast adipose tissue and risk of female breast cancer.

BACKGROUND: Organochlorine compounds, including organochlorine pesticides, have been suggested by some, but not all, studies to be associated with female breast-cancer risk. So far, studies relating organochlorine compounds and breast-cancer risk have mainly focused on polychlorinated biphenyls (PCBs) and dichlorodiphenyltrichloroethane (DDT) as risk factors for female breast cancer. This paper examines the hypothesis that environmental exposure to trans-nonachlor (TNC) and oxychlordane (OCD), a major metabolite of the insecticide chlordane, increases the METHODS: A total of 304 histologically confirmed, incident primary breast-cancer patients and 186 histologically confirmed incident benign breast-disease controls were included in the study between 1994 and 1997. Breast adipose tissue not needed for diagnostic purposes was collected and analysed for TNC, OCD and other organochlorine compounds. A standardised, structured questionnaire was used to obtain information on major known, or suspected, risk factors for breast cancer. RESULTS: The age and lipid-adjusted geometric mean adipose-tissue levels of OCD were similar between the cases [36.4 p.p.b., 95% confidence interval (CI) 34.7-38.2 p.p.b.] and controls (38.0 p.p.b., 95% Cl 35.7-40.6 p.p.b.). The age and lipid-adjusted geometric mean adipose-tissue levels of TNC between the cases (55.5 p.p.b., 95% CI 52.6-58.5 p.p.b.) and controls (58.1 p.p.b., 95% CI 54.2-62.3 p.p.b.) were also similar. There was no association between breast-cancer risk and mean adipose-tissue levels of OCD and TNC. The covariate-adjusted odds ratio (OR) was 0.7 (95% CI 0.4-1.3) for OCD and 1.1 (95% CI 0.6-1.9) for TNC, when the highest quartile was compared with the lowest. The risk also did not vary based on oestrogen or progesterone receptor status or menopausal status. DISCUSSION: We found no significantly increased risk of breast cancer associated with breast adipose-tissue levels of OCD or TNC; this is consistent with recent epidemiological studies, indicating that environmental exposure to organochlorine compounds does not have an overall significant impact on breast-cancer risk.

Adipose Tissue↗
PubMed1999

DDE and DDT in breast adipose tissue and risk of female breast cancer.

A case-control study was conducted in Connecticut from 1994 to 1997 to investigate the relation between dichlorodiphenyldichloroethane (DDE) and dichlorodiphenyltrichloroethane (DDT) exposure and breast cancer risk. Cases and controls were women aged 40-79 years, who had breast-related surgery at the Yale-New Haven Hospital and from whose surgical specimen the authors could obtain at least 0.4 g of breast adipose tissue for chemical analyses. A total of 304 incident breast cancer cases (including 62 in situ carcinomas) and 186 benign breast disease controls were recruited into the study. Tissue levels of DDE and DDT were measured using gas chromatography. Statistical significance for comparisons of mean levels of DDE and DDT was calculated using analysis of variance and rank sum tests. A logistic regression model was used to estimate the association and to control confounding. The age-adjusted geometric mean tissue level of DDE for cases (736.5 ppb) was similar to that for the controls (784.1 ppb). DDT levels were also similar for cases (51.8 ppb) and controls (55.6 ppb). The adjusted odds ratio is 0.9 (95% confidence interval: 0.5, 1.5) for DDE and 0.8 (95% confidence interval: 0.5, 1.5) for DDT when the highest quartile was compared with the lowest. These results do not support an association between adipose tissue levels of DDE and DDT and breast cancer risk.

Adipose Tissue↗
PubMed1999

beta-catenin mutation and expression analysis in ovarian cancer: exon 3 mutations and nuclear translocation in 16% of endometrioid tumours.

The molecular mechanisms involved in the generation of epithelial ovarian cancers are poorly understood, but evidence suggests that the different histological subtypes may arise from independent tumorigenic events. beta-Catenin is emerging as an important oncogene in the transformation of a number of epithelial cancers, and mutations have been reported in a small study of endometrioid ovarian adenocarcinomas. Mutations in the NH(2)-regulatory domain of beta-catenin stabilise the cytoplasmic levels of this protein, which promotes up-regulation of the beta-catenin-T-cell factor-lymphoid enhancer factor transcriptional complex. We report here beta-catenin (CTNNB1) exon 3 mutation analysis in 149 epithelial ovarian carcinomas. This revealed 10/63 (16%) endometrioid ovarian tumours with activating mutations of the beta-catenin gene. All mutations were missense changes within the GSK3beta consensus site, affecting serine residues at codons 33 and 37 and glycine at codon 34. Immuno-histochemical analysis identified cytoplasmic stabilisation and nuclear translocation in those endometrioid tumours with mutations. This phenotypic change was also identified in 3 other endometrioid tumours that did not have somatic mutations within exon 3 of CTNNB1. Stabilisation of the free, monomeric pool of beta-catenin and the probable resulting constitutive activation of its Tcf-associated transcriptional complex appears to be a specific oncogenic event in endometrioid ovarian adenocarcinoma.

Biological Transport↗
PubMed1999

Beta-benzene hexachloride in breast adipose tissue and risk of breast carcinoma.

BACKGROUND: Epidemiologic studies have recently related benzene hexachloride (BHC) to breast carcinoma risk. Experimental studies have also shown that beta-BHC is weakly estrogenic, hence supporting the alleged association. By directly comparing beta-BHC levels in breast adipose tissue from incident breast carcinoma cases and controls, this study examined the hypothesis that exposure to beta-BHC increases the risk of breast carcinoma in females. METHODS: A total of 490 Connecticut women (304 cases and 186 controls) were enrolled in the study during the period 1994-1997. Cases were patients ages 40-79 years with histologically confirmed incident primary breast carcinoma. Controls were patients with histologically confirmed incident benign breast disease. Breast adipose tissue was collected and analyzed for BHC isomers. A linear logistic regression model was used to adjust for potential confounders in estimating the association of exposure with disease. RESULTS: No significant differences in breast adipose tissue levels of beta-BHC were observed between the cases and their controls overall, nor by menopausal status or estrogen and progesterone receptor status of the breast carcinoma cases. A nonsignificant reduced risk was observed among all subjects and among pre- and postmenopausal women when the highest quartile was compared with the lowest. Parous women with higher beta-BHC levels, regardless of lactation status, had a nonsignificantly reduced breast carcinoma risk, whereas a nonsignificantly increased risk was observed among nulliparous women with higher beta-BHC levels, based on very few study subjects. CONCLUSIONS: The results of this study do not support the hypothesis that increasing adipose tissue levels of beta-BHC are associated with an increased risk of breast carcinoma in females.

Adipose Tissue↗
PubMed1999

Triple helix formation: binding avidity of acridine-conjugated AG motif third strands containing natural, modified and surrogate bases opposed to pyrimidine interruptions in a polypurine target.

A critical issue for the general application of triple-helix-forming oligonucleotides (TFOs) as modulators of gene expression is the dramatically reduced binding of short TFOs to targets that contain one or two pyrimidines within an otherwise homopurine sequence. Such targets are often found in gene regulatory regions, which represent desirable sites for triple helix formation. Using intercalator-conjugated AG motif TFOs, we compared the efficacy and base selectivity of 13 different bases or base surrogates in opposition to pyrimidines and purines substituted into selected positions within a paradigm 15-base polypurine target sequence. We found that substitutions closer to the intercalator end of the TFO (positions 4-6) had a more deleterious effect on the dissociation constant (K d) than those farther away (position 11). Opposite T residues at position 11, 3-nitropyrrole or cytosine in the TFO provided adequate binding avidity for useful triplex formation (K ds of 55 and 110 nM, respectively). However, 3-nitropyrrole was more base selective than cytosine, binding to T >/=4 times better than to A, G or C. None of the TFOs tested showed avid binding when C residues were in position 11, although the 3-nitropyrrole-containing TFO bound with a K d of 200 nM, significantly better than the other designs. Molecular modeling showed that the 3-nitropyrrole.T:A triad is isomorphous with the A.A:T triad, and suggests novel parameters for evaluating new base triad designs.

Acridines↗
PubMed1999

Older women's experience of living with chronic leg ulceration.

In this study the authors sought to gain insight into the lives of older women, to focus on the experience of living with leg ulcers and to explore women's views by talking to them about their experiences. Twelve English-speaking women aged over 70 years who had experienced leg ulceration for 3 years or more were interviewed. Analysis of the interview text revealed two overarching themes: (i) gaining and maintaining control over vulnerable limb(s); and (ii) lifestyle consequences of chronic leg ulceration and impaired mobility. These themes contained several subthemes including: (i) nagging pain; (ii) self-expertise and infection; (iii) leakage, smell and embarrassment; (iv) fighting for skin and limb integrity; (v) wearing non-preferred apparel; (vi) loneliness; and (vii) coping, determination and hope. The findings of this research show that elderly women who live with leg ulcers experience multiple consequences. While the everyday problems of living with an unhealed would are addressed by the community nurse, other more subtle consequences may be overlooked. Recognition of the complex and sometimes hidden concerns of these women could help to avert the sense of helplessness which currently exists.

Adaptation, Psychological↗
PubMed1999

Relationships of cerebral MRI findings to ultrasonographic carotid atherosclerosis in older adults : the Cardiovascular Health Study. CHS Collaborative Research Group.

Cerebral magnetic resonance imaging (MRI) has demonstrated a high prevalence of infarct-like lesions, white matter hyperintensities, and evidence of cerebral atrophy in older adults. While these findings are generally believed to be related to ischemia and atherosclerosis, their relationship to atherosclerosis in the carotid arteries remains to be explored. Study subjects were part of the multicenter Cardiovascular Health Study, a cross-sectional study of 3502 women and men >/=65 years of age undergoing cranial MRI and carotid ultrasonography. MRI infarcts were detected in 1068 participants (29.3%) and measurable carotid plaque in 2745 (75.3%). MRI infarcts, ventricular and sulcal widening, and white matter score were strongly associated with carotid intimal-medial thickness (IMT) and stenosis degree after adjustment for age and sex (all P<0. 01). Associations with plaque characteristics were less strong and less consistent; MRI infarcts were weakly associated only with surface irregularity, and ventricular size was weakly associated only with lesion density (both P<0.04). In contrast, sulcal widening was strongly related to plaque characteristics, with scores being higher in those with heterogeneous and irregular plaque (both P<0. 009). Adjustment for other risk factors, and for carotid IMT/stenosis, removed associations of MRI findings with plaque characteristics except for weak relationships remaining between MRI infarcts and surface irregularity and between sulcal score and heterogeneous plaque (both P<0.03). MRI abnormalities show strong and consistent relationships with increasing carotid IMT and stenosis degree but less strong associations with plaque characteristics, especially after adjusting for IMT and stenosis.

Aged↗
PubMed1999

Issues of consent in colonoscopy: if a patient says 'stop' should we continue?

Colonoscopy is generally performed under intravenous sedation, which may alter a patient's responses and perception. What should be done if, during the procedure, a patient withdraws the consent previously given? The views of gastroenterologists and patients were ascertained by mailing questionnaires to 100 members of the British Society of Gastroenterology and to 100 patients who had undergone colonoscopy with intravenous sedation. Only 1 of 59 eligible consultants who replied said they would stop the procedure after a single request, but a further 51 would stop if repeatedly asked to do so. Of the remaining 7 who would complete the procedure, 1 nevertheless believed that a sedated patient is capable of making a rational decision. Of the 51 patients who returned a usable questionnaire, 25 thought that the procedure should be stopped immediately following a request, while 26 felt that the doctor should continue. The divergent and sometimes inconsistent views found in this study highlighted the need for further clarification of the issue of informed consent for procedures conducted with the patient under sedation.

Anesthesia, Intravenous↗
PubMed1999

BRCA1/BRCA2 germline mutations in locally recurrent breast cancer patients after lumpectomy and radiation therapy: implications for breast-conserving management in patients with BRCA1/BRCA2 mutations.

PURPOSE: Breast cancer patients treated conservatively with lumpectomy and radiation therapy (LRT) have an estimated lifetime risk of local relapse (ipsilateral breast tumor recurrence [IBTR]) of 10% to 15%. For breast cancer patients carrying BRCA1 or BRCA2 (BRCA1/2) mutations, the outcome of treatment with LRT with respect to IBTR has not been determined. In this study, we estimate the frequency of BRCA1/2 mutations in a study of breast cancer patients with IBTR treated with LRT. PATIENTS AND METHODS: Between 1973 and 1994, there were 52 breast cancer patients treated with LRT who developed an IBTR within the prior irradiated breast and who were willing to participate in the current study. From our database, we also identified 52 control breast cancer patients treated with LRT without IBTR. The control patients were individually matched to the index cases with respect to multiple clinical and pathologic parameters. Lymphocyte DNA specimens from all 52 locally recurrent patients and 15 of the matched control patients under age 40 were used as templates for polymerase chain reaction amplification and dye-primer sequencing of exons 2 to 24 of BRCA1, exons 2 to 27 of BRCA2, and flanking intron sequences. RESULTS: After LRT, eight (15%) of 52 breast cancer patients had IBTR with deleterious BRCA1/2 mutations. By age, there were six (40%) of 15 patients with IBTR under age 40 with BRCA1/2 mutations, one (9.0%) of 11 between ages 40 and 49, and one (3.8%) of 26 older than age 49. In comparison to the six (40%) of 15 of patients under age 40 with IBTR found to have BRCA1/2 mutations, only one (6.6%) of 15 matched control patients without IBTR and had a BRCA1/2 mutation (P =.03). The median time to IBTR for patients with BRCA1/2 mutations was 7.8 years compared with 4.7 years for patients without BRCA1/2 mutations (P =.03). By clinical and histologic criteria, these relapses represented second primary tumors developing in the conservatively treated breast. All patients with BRCA1/2 mutations and IBTR underwent successful surgical salvage mastectomy at the time of IBTR and remain alive without evidence of local or systemic progression of disease. CONCLUSION: In this study, we found an elevated frequency of deleterious BRCA1/2 mutations in breast cancer patients treated with LRT who developed late IBTR. The relatively long time to IBTR, as well as the histologic and clinical criteria, suggests that these recurrent cancers actually represent new primary breast cancers. Early onset breast cancer patients experiencing IBTR have a disproportionately high frequency of deleterious BRCA1/2 mutations. This information may be helpful in guiding management in BRCA1 or BRCA2 patients considering breast-conserving therapy.

Adult↗
PubMed1999

Environmental exposure to hexachlorobenzene (HCB) and risk of female breast cancer in Connecticut.

Earlier studies have provided inconclusive results relating hexachlorobenzene (HCB), an organochlorine fungicide, to female breast cancer risk. The current study, with a total of 304 breast cancer cases and 186 controls recruited in Connecticut between 1994 and 1997, examined the association by directly comparing breast adipose tissue levels of HCB between incident breast cancer cases and noncancer controls. The cases and controls were patients who had breast biopsies or surgery at the Yale-New Haven Hospital (New Haven, CT) and histologically diagnosed either as breast cancer or benign breast disease. Information on major known or suspected risk factors for breast cancer was obtained through in-person interview by trained interviewers. No significant difference in mean breast adipose tissue levels of HCB was observed between breast cancer patients (21.0 ppb) and controls (19.1 ppb) in this large case-control study. The risk also did not vary significantly by menopausal status, estrogen or progesterone receptor status of the breast cancer cases, breast cancer histology, stage of diagnosis, or type of benign breast disease. Among parous women who reported ever breast feeding, an odds ratio (OR) of 0.5 [95% confidence interval (CI), 0.2-1.4] was observed when the highest quartile was compared with the lowest quartile. However, no association was observed among parous women who reported never breast feeding (OR = 0.7; 95% CI, 0.3-1.7 for the fourth quartile). For nulliparous women, the adjusted OR was 2.1 (95% CI, 0.5-8.8) for the third tertile when compared with the lowest based on few subjects. Therefore, our study does not support a positive association between environmental exposure to HCB and risk of breast cancer.

Adipose Tissue↗
PubMed1999

Improving the detection of postnatal depression.

Women are at risk of developing mental health problems in the postnatal period. Health visitors play an important role in the detection of postnatal depression. The Edinburgh Postnatal Depression Scale can be used to screen all new mothers.

Algorithms↗
PubMed1998

Frequent loss of heterozygosity and three critical regions on the short arm of chromosome 8 in ovarian adenocarcinomas.

Many chromosomal regions undergo loss of heterozygosity (LOH) in ovarian adenocarcinomas but few of the target regions have been finely mapped. One of the chromosome arms likely to harbour one or more tumour suppressor genes inactivated in ovarian cancer is the short arm of chromosome 8 which is frequently deleted in many other solid tumours. We have examined a large panel of microsatellite markers on 8p for LOH in 53 ovarian adenocarcinomas. LOH was observed in 27 tumours (51%), with a significant trend towards a higher frequency of LOH in more advanced tumours. Detailed examination of nine tumours with partial deletions defined three regions of overlap, two in 8p23 and one in 8p22, which suggests that there might be as many as three tumour or metastasis suppressor genes on 8p which are inactivated during ovarian tumorigenesis. LOH on 8p was significantly associated with 9p LOH which suggests that inactivation of target genes on these chromosomes may be cooperative events.

Adenocarcinoma↗
PubMed1998

Combinatorial library diversity: probability assessment of library populations.

A method is described for measuring the diversity of combinatorial oligonucleotide libraries that entails extrapolating the base composition of a co-synthesized model library (dNC, N = A, C, G, T) to that of a multibase library template. The base composition of dNC was measured by HPLC. The ability of dNC to predict the base composition of a multibase library template was corroborated by measuring the composition of a 12 base combinatorial library. The base composition of the 12 base library was determined by several template dependent incorporation assays: measurement of restriction fragment specific activities from polymerase incorporation/restriction enzyme digests, template directed radionucleotide primer extension and quantitative dideoxynucleotide sequencing. Additionally, a convention for describing oligomeric combinatorial library (OCL) diversity is proposed. The convention uses a quantity termed the diversity quotient (Qd) to describe library breadth and the mole fraction of the least represented monomeric unit of the OCL to calculate minimum library quantity requirements. Similar methods/conventions could presumably be developed/adopted for non-nucleic acid libraries.

Base Composition↗