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Biomedical subjects

B Ward

Publications and source records attributed to B Ward.

At least 55 records · Page 3Linked to original sources

Whole blood selenium in exudative age-related maculopathy.

PURPOSE: We tested whether exudative ARM was associated with low whole blood levels of selenium (Se). METHODS: Blood samples, drawn from 10 exudative ARM patients (61.2-76.1 yr) and 9 healthy-eyed (66.9-75.1 yr) subjects, were analyzed by atomic absorption spectroscopy. RESULTS: Selenium concentration was significantly lower in the ARM group (186.6 microg/l) than in controls (207.0 microg/l). Because many ARM patients took Se supplements, we tested the effect on blood Se of 80 microg per day of sodium selenate. We found no enduring effects of supplementation for healthy-eyed, younger adults. CONCLUSIONS: Significant group differences in this preliminary study indicate a larger-scale study of blood Se concentration in exudative ARM patients is warranted. If the effect of Se supplementation on the progression of exudative ARM is tested in future trials, it will be important to use organic Se, to identify the components of blood affected, and to observe protocol for at least six months.

Adult↗

Are we telling patients enough? A pilot study to assess patient information needs in a gastroenterology outpatient department.

OBJECTIVE: To define whether gastroenterology patients wish to receive more information concerning many aspects of their illness and to elicit their attitude after receiving written communication from their hospital practitioner. METHODS: In stage 1, 73 gastroenterology patients were interviewed and completed a structured questionnaire after their hospital outpatient visit, to assess whether they would like to receive more information about their condition. Stage 2 involved posting a copy of the general practitioner's letter, dictated in the clinic, to the patient and assessing their opinion of its value, by using a second questionnaire. In stage 3 a group of outpatients received a letter specifically prepared for them which summarized the outcome of their clinic visit (with avoidance of medical terms) and they again completed a questionnaire. RESULTS: More than 75% of patients wished to receive written communication from their hospital practitioner. Ninety percent wanted to know more about diagnostic tests and 92% requested more information about their medication. Ninety percent of patients who received a copy of their GP's letter claimed to understand its contents and felt it was beneficial. Ninety four percent wanted the service to continue. However, there was no advantage in preparing a special letter for patients compared with a simple copy of that sent to their GP. CONCLUSION: There is considerable interest amongst gastroenterology patients concerning their diagnosis and the management of their disease. The provision of simplified letters about their outpatient management does not seem to have any advantage over simply providing copies of all relevant correspondence sent to GPs.

Attitude↗

Comparison of low molecular weight heparin (Fragmin) with sodium heparin for prophylaxis against postoperative thrombosis in women undergoing major gynaecological surgery.

A randomized controlled trial was undertaken comparing the efficacy and safety of low molecular weight (LMW) heparin (Fragmin) with sodium heparin for prophylaxis against postoperative thromboembolic disease after major gynaecological surgery. Women were randomized to receive subcutaneous injections of 5,000 U of either once daily LMW heparin or twice daily sodium heparin. A total of 566 women were recruited, of whom 552 completed the study. Most women (461) had malignant disease and 430 of these underwent radical surgery. The remainder underwent major, but not radical surgery. There were 5 thromboembolic events in the LMW heparin group and 2 in the sodium heparin group, with no significant difference between these groups. No significant difference was found in the incidence of intraoperative or postoperative transfusion in the 2 groups. The decision of which heparin to use in routine practice cannot be made on clinical grounds.

Anticoagulants↗

BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing.

CONTEXT: A mutation in the BRCA1 gene may confer substantial risk for breast and/or ovarian cancer. However, knowledge regarding all possible mutations and the relationship between risk factors and mutations is incomplete. OBJECTIVES: To identify BRCA1 mutations and to determine factors that best predict presence of a deleterious BRCA1 mutation in patients with breast and/or ovarian cancer. DESIGN: A complete sequence analysis of the BRCA1 coding sequence and flanking intronic regions was performed in 798 women in a collaborative effort involving institutions from the United States, Italy, Germany, Finland, and Switzerland. PARTICIPANTS: Institutions selected 798 persons representing families (1 person for each family) thought to be at elevated a priori risk of BRCA1 mutation due to potential risk factors, such as multiple cases of breast cancer, early age of breast cancer diagnosis, and cases of ovarian cancer. No participant was from a family in which genetic markers showed linkage to the BRCA1 locus. MAJOR OUTCOME MEASURES: Sequence variants detected in this sample are presented along with analyses designed to determine predictive characteristics of those testing positive for BRCA1 mutations. RESULTS: In 102 women (12.8%), clearly deleterious mutations were detected. Fifty new genetic alterations were found including 24 deleterious mutations, 24 variants of unknown significance, and 2 rare polymorphisms. In a subset of 71 Ashkenazi Jewish women, only 2 distinct deleterious mutations were found: 185delAG in 17 cases and 5382insC in 7 cases. A bias in prior reports for mutations in exon 11 was revealed. Characteristics of a patient's specific diagnosis (unilateral or bilateral breast cancer, with or without ovarian cancer), early age at diagnosis, Ashkenazi Jewish ethnicity, and family history of cancer were positively associated with the probability of her carrying a deleterious BRCA1 mutation. CONCLUSIONS: Using logistic regression analysis, we provide a method for evaluating the probability of a woman's carrying a deleterious BRCA1 mutation for a wide range of cases, which can be an important tool for clinicians as they incorporate genetic susceptibility testing into their medical practice.

Breast Neoplasms↗

Tubal sterilisation, hysterectomy and decreased risk of ovarian cancer. Survey of Women's Health Study Group.

We have examined the effect of tubal sterilisation and hysterectomy on risk of ovarian cancer in a large case-control study in eastern Australia involving 824 women aged 18-79 years, diagnosed with epithelial ovarian cancer between 1990 and 1993, and 855 controls randomly selected from the electoral roll. Relative risks for ovarian cancer were estimated using multiple categorical regression to adjust for age, parity, oral contraceptive use and other risk factors. Tubal sterilisation was associated with a 39% reduction in risk of ovarian cancer (RR 0.61, 95% CI 0.46-0.85) and hysterectomy with a 36% reduction (RR 0.64, 95% CI 0.48-0.85). Risk remained low 25 years after surgery and was reduced irrespective of sterilisation technique, and estimates were similar among various types of epithelial ovarian cancer. The greatest reduction (74%) was observed among women with primary peritoneal tumours. Pelvic infection and use of vaginal sprays or contraceptive foams were not related to ovarian cancer, while use of talc in the perineal region slightly but significantly increased risk among women with patent fallopian tubes. Reportedly heavy or painful menses, perhaps associated with retrograde flow, were associated with ovarian cancer, and reduction in risk of disease after hysterectomy was greatest among women who had heavy periods. Our findings support the theory that contaminants from the vagina, such as talc, and from the uterus, such as endometrium, gain access to the peritoneal cavity through patent fallopian tubes and may enhance the malignant transformation of ovarian surface epithelium. Surgical tubal occlusion may reduce the risk of ovarian cancer by preventing the access of such agents.

Adolescent↗

Rare mutations and no hypermethylation at the CDKN2A locus in epithelial ovarian tumours.

The tumour-suppressor gene CDKN2A (p16, MTS1, CDK4I) encodes a cell cycle-regulatory protein and is located on chromosome 9p21, a region deleted in a wide variety of human cancers. To determine the role of the CDKN2A gene in the development of ovarian adenocarcinomas, we examined a large series of benign, low malignant potential (LMP) and invasive ovarian neoplasms for evidence of loss of heterozygosity (LOH), homozygous deletions, point mutations and hypermethylation of the CDKN2A locus. We have previously reported LOH on 9p in 45% of malignant ovarian neoplasms and a smaller percentage of benign and LMP tumours. In the current study, 6 malignant tumours were identified with partial deletions of 9p21. In 5 of these, the CDKN2A gene lays within the minimal deleted region. Homozygous deletions of CDKN2A were observed in only 2/88 invasive ovarian tumours and in 5/11 ovarian cancer cell lines. Of 15 primary ovarian tumours analyzed, one nonsense mutation was identified in a mucinous LMP tumour. No evidence of hypermethylation of the CDKN2A gene was found in 50 primary ovarian adenocarcinomas nor in 3 ovarian cancer cell lines. In conclusion, homozygous deletions, mutations and the de novo methylation of 5' CpG island are not frequent modes of inactivation of the CDKN2A gene in ovarian cancer. The target of 9p LOH in ovarian adenocarcinomas is therefore unknown.

Blotting, Southern↗

Analysis of loss of heterozygosity and KRAS2 mutations in ovarian neoplasms: clinicopathological correlations.

The molecular events that give rise to ovarian epithelial neoplasms are not well understood. In particular, it is not known whether adenocarcinomas arise from benign or low malignant potential (LMP) precursors. We have examined a large series of benign (25) and LMP (31) ovarian tumors for loss of heterozygosity (LOH) at multiple loci on 17 chromosomes. LOH was observed in benign tumors on chromosomes 6 (14%) and 9 (5%) and on the X chromosome (33%) only. LOH on these chromosomes was also detected in a small number of LMP neoplasms, suggesting that these may derive sometimes from benign precursors. In addition, we examined LOH in 93 adenocarcinomas. Analysis of associations between LOH events showed that LOH on chromosomes 5 and 17 (P = 0.0002) and on chromosomes 17 and 18 (P = 0.00007) were associated significantly with each other, which suggests that these may represent cooperative, progressive events. No novel significant associations were identified between LOH events and stage, grade, or histology, which would indicate the existence of genetic heterogeneity in ovarian neoplasms. KRAS2 mutations were detected more often in LMP neoplasms than in malignant tumors (P = 0.004) and were detected more often in Stage I/II malignant tumors than in Stage III/IV malignant tumors (P = 0.033), suggesting that LMP tumors with KRAS2 mutations are unlikely to progress to frank malignancy. Univariate (but not multivariate) survival analysis showed that LOH of chromosomes 11 (P = 0.039) and 17 (P = 0.04) was associated with a significantly worse prognosis. Replication of these novel findings is necessary, and the identification, isolation, and characterization of the critical genes affected by LOH will determine their importance in the pathogenesis of ovarian malignancies.

Chromosome Deletion↗

Developing and evaluating a Spanish TEL-MED message on breast cancer.

A Spanish TEL-MED message on breast cancer was designed for Delaware. The message, created from a focus group of Latino professionals and volunteers from the American Cancer Society, Delaware Division, provides information for Latinas on breast cancer. In one minute, forty-five seconds the message answers in Spanish the following questions: (1) What are the symptoms of breast cancer? (2) What can women do to protect themselves against breast cancer? (3) What is a mammogram? (4) When should I have a mammogram done? (5) How much does a mammogram cost? The message also provides information on where to obtain low cost or free mammograms. A pamphlet in Spanish, featuring a picture of an elderly Latina listening to the phone message, describes how to access the tape. The message targets older Latinas who prefer to speak Spanish. The American Cancer Society, Delaware Division, distributed a press release featuring the Spanish TEL-MED and circulated the pamphlets to Latino organizations and churches. Evaluation of the TEL-MED message in Spanish suggests it to be an innovative way to reach older Latino women. The Spanish message on breast cancer was requested 58% as often as the breast cancer message in English, and 193% more often than the epilepsy tape in Spanish. The peak period for the calls to the Spanish TEL-MED message occurred after the initial promotional activities. These findings suggest that education of older Latinas on breast cancer can be augmented by the use of TEL-MED message in Spanish. They further suggest that the combination of TEL-MED and mass media campaign had a positive effect on Spanish speaking users of the TEL-MED.

Aged↗

Low proportion of BRCA1 and BRCA2 mutations in Finnish breast cancer families: evidence for additional susceptibility genes.

One hundred breast and breast-ovarian cancer families identified at the Helsinki University Central Hospital in southern Finland and previously screened for mutations in the BRCA2 gene were now analyzed for mutations in the BRCA1 gene. The coding region and splice boundaries of BRCA1 were analyzed by protein truncation test (PTT) and heteroduplex analysis (HA)/SSCP in all 100 families, and 70 were also screened by direct sequencing. Contrary to expectations based on Finnish population history and strong founder effects in several monogenic diseases in Finland, a wide spectrum of BRCA1 and BRCA2 mutations was found. In the BRCA1 gene, 10 different protein truncating mutations were found each in one family. Six of these are novel Finnish mutations and four have been previously found in other European populations. Six different BRCA2 mutations were found in 11 families. Altogether only 21% of the breast cancer families were accounted for by mutations in these two genes. Linkage to both chromosome 17q21 (BRCA1) and 13q12 (BRCA2) was also excluded in a subset of seven mutation-negative families with four or more cases of breast or ovarian cancer. These data indicate that additional breast and breast-ovarian cancer susceptibility genes are likely to be important in Finland.

Adult↗

Are cancers of the salivary gland increasing? Experience from Connecticut, USA.

BACKGROUND: Recent studies indicate that cancers of the salivary gland are increasing, and the factors responsible for the increase are unknown. Artefactual changes, such as shift in classifying cancers of the floor of the mouth to cancers of the salivary gland, could affect the time trend for salivary gland cancer. METHODS: The current study examined the time trends for cancers of the salivary gland and for cancers of the floor of the mouth and lower gum by using Connecticut Tumor Registry data for the time period 1935-1992. A regression model was used to identify the components of birth cohort, period and age as determinants of the observed time trend. RESULTS: Cancers of the salivary gland have recently increased in Connecticut, with a relative risk of 1.48 (95% CI: 1.06-2.08) for females in 1990-1992 compared to 1980-1984, and a comparable relative risk of 1.60 (95% CI: 1.16-2.22) for males. The increase was found in all age groups 40 and over, particularly among those aged 70 and over. The results from age-period-cohort modelling show a recent upturn in the trend for period slopes, with no clear increase from recent birth cohorts, which is consistent with the results from univariate analyses suggesting no clear increase among those under 40 years of age. CONCLUSION: Our results suggest that artifactual changes, such as a shift in designation of cancer sites, increasing use of the needle aspirate biopsies, and greater access to medical care for the elderly, may have largely contributed to the rising trend. The known risk factors, radiation exposure and a history of a prior cancer, can hardly explain the observed increase. The Epstein-Barr virus infection has only been associated with certain types of rare squamous cell carcinomas of the salivary gland in the Eskimo population. The AIDS epidemic also cannot explain why older age groups have accounted for most of the increase in incidence of the disease. An examination of the incidence rates for cancers of the salivary gland from other populations may help to clarify the issue.

Adult↗

Nonlinear propagation applied to the improvement of resolution in diagnostic medical ultrasound.

Medical B-mode scanners operating under conditions typically encountered during clinical work produce ultrasonic wave fields that undergo nonlinear distortion. In general, the resulting harmonic beams are narrower and have lower sidelobe levels than the fundamental beam, making them ideal for imaging purposes. This work demonstrates the feasibility of nonlinear harmonic imaging in medical scanners using a simple broadband imaging arrangement in water. The ultrasonic system comprises a 2.25-MHz circular transducer with a diameter of 38 mm, a membrane hydrophone, also with a diameter of 38 mm, and a polymer lens with a focal length of 262 mm. These components are arranged coaxially giving an imaging geometry similar to that used in many commercial B-scanners, but with a receiver bandwidth sufficient to record the first four harmonics. A series of continuous wave and pulse-echo measurements are performed on a wire phantom to give 1-D transverse pressure profiles and 2-D B-mode images, respectively. The reflected beamwidths wn decrease as wn/W1 = 1/n0.78, where n is the harmonic number, and the reflected sidelobe levels fall off quickly with increasing n. In imaging terms, these effects correspond to a large improvement in lateral resolution and signal-to-clutter ratio for the higher harmonics.

Equipment Design↗

The views of medical students and junior doctors on pre-graduate clinical teaching.

A total of 277 third and fourth year medical students and 304 house officers and senior house officers were asked to prioritise the content and methods of clinical teaching. Response rates were poor, but similar to that in market surveys. Bedside teaching and medical clerking were considered the most valuable methods of teaching and training in practical procedures such as venepunctures and urinary catheterisation was seen as valuable. The design of new curricula in medical education will need to accommodate the views of its clients.

Attitude of Health Personnel↗

Reappraisal of the role of axillary lymph node dissection in the conservative treatment of breast cancer.

PURPOSE: The purpose of this study was (1) to review systemic therapy practice patterns to assess how information regarding nodal status currently influences systemic therapy decisions, and (2) to review long-term outcome of patients who do not undergo axillary dissection compared with patients who do. METHODS AND MATERIALS: For the current practice patterns portion of the study, the records of 292 patients who presented in the past 3 years with invasive breast cancer and underwent conservative surgery were reviewed to determine systemic therapy administered with respect to patient age, primary tumor size, clinical nodal status, and presenting symptoms. For the long-term outcome portion of the study, the records of 955 patients with invasive breast cancer who underwent conservative surgery and radiation therapy before December 1989 were reviewed. Patient characteristics and outcome of those patients who underwent axillary dissection (n = 565, 59%) were compared with a cohort of patients treated during the same era who did not undergo axillary dissection (n = 390, 41%). RESULTS: For the current practice-patterns cohort, information regarding nodal status appeared to influence adjuvant systemic therapy for those patients less than 50 years of age and for those patients with palpable masses who were older than 50. Patients older than 50 with nonpalpable mammographically detected tumors have a low probability of nodal involvement and information regarding nodal status rarely changed therapy in this group of patients. In the long-term outcome study, there were no significant differences in the rates of distant metastasis, disease-free survival, or overall survival between those patients who underwent lymph node dissection and those who did not. CONCLUSION: For selected patients, axillary lymph node dissection appears to have little influence on subsequent management and long-term outcome. These data suggest that it is time to reassess the role of axillary lymph node dissection in patients who undergo conservative surgery and radiation therapy.

Actuarial Analysis↗

Allelic loss on chromosome 7q in ovarian adenocarcinomas: two critical regions and a rearrangement of the PLANH1 locus.

The presence of a tumour suppressor gene on chromosome 7q is indicated by cytogenetic, loss of heterozygosity (LOH) and chromosome transfer studies. One candidate gene in this region is Plasminogen Activator Inhibitor-1 (PAI-1). The PAI-1 gene product is involved in proteolysis and may therefore influence tumour spread and invasion. We have analysed a series of 139 ovarian epithelial tumours at four loci in the region 7q21-q31 which includes the PAI-1 gene. The highest rates of loss were found in malignant tumours (FIGO stages I-IV) at markers D7S471 (38%, 20/52 informative cases) and D7S522 (34%, 15/44). No loss was seen in benign tumours and only one out of 27 (4%) informative LMP tumours demonstrated LOH. The smallest region of overlap (SRO) lies between D7S471 and PAI-1. We also identified a rearrangement in one tumour in the PAI-1 gene, suggesting that this may be the inactivated gene in this region. In addition LOH at the more distal marker, D7S522, which lies outside the SRO, shows significant association with stage (P=0.0343) and with LOH on chromosome 13 (P=0.0024). This is in contrast to all other markers examined. These data suggest the presence of two critical regions on 7q which may be important in subsets of epithelial ovarian tumours.

Adenocarcinoma↗

Type IIS restriction enzyme footprinting I. Measurement of a triple helix dissociation constant with Eco57I at 25 degrees C.

A method is described to measure triple helix dissociation constants by inhibiting the cleavage of a plasmid constructed to contain a target sequence for the triplex forming oligonucleotide (TFO) dT20 by the type IIS restriction enzyme Eco57I. The method relies upon the TFO's ability to block the cleavage reaction by occupying the enzymes cleavage site but not its specific binding sequence. Using this protocol, the dissociation constant for dT20 bound to its target was 0.16 +/- 0.01 microM at 25 degrees C. The accuracy of this experiment was demonstrated by measuring the Kd of an affinity cleavage TFO using Eco57I and Quantitative Affinity Cleavage Titration. Type IIS restriction endonuclease footprinting should be useful for the qualitative and quantitative investigation of ligand-DNA interactions.

Base Sequence↗