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Biomedical subjects

D Ford

Publications and source records attributed to D Ford.

At least 73 records · Page 4Linked to original sources
PubMed1995

Recovery of human immunodeficiency virus from peritoneal dialysis effluent.

Increasing numbers of HIV-infected patients who have ESRD are being treated with continuous ambulatory peritoneal dialysis (CAPD). To investigate the potential infectious nature of peritoneal dialysate (PD), the peritoneal dialysis effluent was studied in 14 patients on CAPD who were known to be HIV antibody positive. Peripheral blood mononuclear cells and the sediment of PD were obtained from each patient and subjected to a qualitative microculture assay using a coculture of patient cells or PD fluid with peripheral blood mononuclear cells from non-HIV-infected individuals. Samples from the coculture were collected twice weekly for HIV P24 antigen determination as a marker of viral replication. PD, white blood cell and red blood cell counts, and peripheral blood CD4 lymphocyte counts were also measured. All 14 patients developed a positive blood culture by Day 3. Twelve of the 14 patients developed a positive PD fluid culture. The mean CD4 count was 310 cells/mm3. No patient had clinical or cellular evidence of peritonitis at the time of fluid sampling. These data indicate that peritoneal dialysis effluent from patients who are HIV antibody positive is potentially infectious.

Adult↗
PubMed1995

An evaluation of genetic heterogeneity in 145 breast-ovarian cancer families. Breast Cancer Linkage Consortium.

The breast-ovary cancer-family syndrome is a dominant predisposition to cancer of the breast and ovaries which has been mapped to chromosome region 17q12-q21. The majority, but not all, of breast-ovary cancer families show linkage to this susceptibility locus, designated BRCA1. We report here the results of a linkage analysis of 145 families with both breast and ovarian cancer. These families contain either a total of three or more cases of early-onset (before age 60 years) breast cancer or ovarian cancer. All families contained at least one case of ovarian cancer. Overall, an estimated 76% of the 145 families are linked to the BRCA1 locus. None of the 13 families with cases of male breast cancer appear to be linked, but it is estimated that 92% (95% confidence interval 76%-100%) of families with no male breast cancer and with two or more ovarian cancers are linked to BRCA1. These data suggest that the breast-ovarian cancer-family syndrome is genetically heterogeneous. However, the large majority of families with early-onset breast cancer and with two or more cases of ovarian cancer are likely to be due to BRCA1 mutations.

Adult↗
PubMed1995

Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium.

Dominant predisposition to early-onset breast cancer and/or ovarian cancer in many families is known to be the result of germ-line mutations in a gene on chromosome 17q, known as BRCA1. In this paper we use data from families with evidence of linkage to BRCA1 to estimate the age-specific risks of breast and ovarian cancer in BRCA1-mutation carriers and to examine the variation in risk between and within families. Under the assumption of no heterogeneity of risk between families, BRCA1 is estimated to confer a breast cancer risk of 54% by age 60 years (95% confidence interval [CI] 27%-71%) and an ovarian cancer risk of 30% by age 60 years (95% CI 8%-47%). Similar lifetime-risk estimates are obtained by examining the risks of contralateral breast cancer and of ovarian cancer, in breast cancer cases in linked families. However, there is significant evidence of heterogeneity of risk between families; a much better fit to the data is obtained by assuming two BRCA1 alleles, one conferring a breast cancer risk of 62% and an ovarian cancer risk of 11% by age 60 years, the other conferring a breast cancer risk of 39% and an ovarian cancer risk of 42%, with the first allele representing 71% of all mutations (95% CI 55%-87%). There is no evidence of clustering of breast and ovarian cancer cases within families.

Adult↗
PubMed1995

Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence.

The majority of multiple-case families that segregate both breast and ovarian cancer in a dominant fashion are due to mutations in the BRCA1 gene on chromosome 17q. In this paper, we have combined penetrance estimates for BRCA1 with the results of two population-based genetic epidemiological studies to estimate the gene frequency of BRCA1. On the assumption that the excess risk of ovarian cancer in first degree relatives of breast cancer patients and the breast cancer excess in relatives of ovarian cancer patients are both entirely accounted for by BRCA1, we estimate that the BRCA1 gene frequency is 0.0006 (95% confidence interval [O.002-0.002]) and that the proportion of breast cancer cases in the general population due to BRCA1 is 5.3% below age 40 years, 2.2% between ages 40 and 49 years, and 1.1% between ages 50 and 70 years. The corresponding estimates for ovarian cancer are 5.7%, 4.6%, and 2.1%, respectively. Our results suggest that the majority of breast cancer families with less than four cases and no ovarian cancer are not due to rare highly penetrant genes such as BRCA1 but are more likely to be due either to chance or to more common genes of lower penetrance.

Adult↗
PubMed1994

Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13.

A small proportion of breast cancer, in particular those cases arising at a young age, is due to the inheritance of dominant susceptibility genes conferring a high risk of the disease. A genomic linkage search was performed with 15 high-risk breast cancer families that were unlinked to the BRCA1 locus on chromosome 17q21. This analysis localized a second breast cancer susceptibility locus, BRCA2, to a 6-centimorgan interval on chromosome 13q12-13. Preliminary evidence suggests that BRCA2 confers a high risk of breast cancer but, unlike BRCA1, does not confer a substantially elevated risk of ovarian cancer.

Breast Neoplasms↗
PubMed1994

Undetected eye disease in a primary care clinic population.

BACKGROUND: Population-based data have indicated that a significant proportion of persons with undiagnosed ocular disease in the community are regular users of general medical services. This, combined with the high prevalence of chronic medical disorders known to be risk factors for ocular disease in such clinics, makes them an attractive site for screening. METHODS: The prevalence of ocular disease was estimated in a sample of 405 general medicine patients attending an adult primary care clinic in an urban teaching hospital. RESULTS: Overall, 205 (50.6%) of 405 patients were found to have clinically important ocular pathology. One third of those affected (n = 68) were unaware of their eye disease, and 26% (n = 18) of these 68 patients required immediate medical or surgical intervention. Patients 65 years or older (odds ratio [OR], 1.76), in fair or poor general health (OR, 1.78), with diabetes mellitus (OR, 2.07), or with self-reported fair or poor vision (OR, 3.03), were at increased risk for the presence of ocular disease. Among patients with eye disease, those who had no insurance coverage for eye care (OR, 3.45), those who had not had an eye examination during the previous 2 years (OR, 4.03), and those whose last eye examination was performed by an optometrist (OR, 7.25, reference ophthalmologist) were more likely to not be aware of their eye disease. CONCLUSIONS: Our results underscore the importance of screening for ocular disease in primary health care settings, especially for patients who are older than 65 years, are in poor health, report poor vision, have had infrequent eye examinations, or have inadequate insurance coverage for eye care.

Adult↗
PubMed1994

Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium.

Germline mutations in a gene on chromosome 17q known as BRCA1 are responsible for a large proportion of inherited predispositions to breast and ovarian cancer. In 33 families with evidence of linkage to BRCA1, we estimated the risks of breast and ovarian cancer from the occurrence of second cancers in individuals with breast cancer, and examined the risks of other cancers in BRCA1 carriers. 26 contralateral primary breast cancers occurring more than 3 years after a first breast cancer were observed before age 70, giving an estimated cumulative risk of breast cancer in gene carriers of 87% by age 70.23 primary ovarian cancers occurred in women with a previous breast cancer, resulting in an estimated cumulative risk of ovarian cancer of 44% by age 70.87 cancers other than breast or ovarian cancer were observed in individuals with breast or ovarian cancer and their first-degree relatives compared with 69.3 expected, based on national incidence rates. Significant excesses were observed for colon cancer (estimated relative risk [RR] to gene carriers 4.11 [95% CI 2.36-7.15]) and prostate cancer (3.33 [1.78-6.20]). No significant excesses (or deficits) were noted for cancers of other sites. Our study provides estimates of breast and ovarian cancer risks which are useful for counselling BRCA1-mutation carriers. It also shows that carriers are at increased risk of colon and prostate cancer, which may be of clinical significance in certain families if the risks are associated with specific mutations.

Adult↗
PubMed1994

Torque of trunk flexion and trunk flexion with axial rotation in healthy men and women.

The purpose of this study was to determine normal values for torque of trunk flexion and trunk flexion with axial rotation. Eighty-two healthy subjects (39 men, 43 women) were tested for isometric torque of trunk flexion at four angles, and eccentric and concentric torque at 30 degrees/sec. All tests were performed in three positions of axial rotation: neutral rotation, trunk rotated 30 degrees to the right, and trunk rotated 30 degrees to the left. The results of two separate three-way analyses of variance (gender vs. position vs. angle/contraction) indicated that the torque of men was greater than that of women, eccentric torque was greater than concentric, and the torque in neutral rotation was greater than in right or left rotation. Isometric torque decreased with increased trunk flexion. Regression and correlation analyses demonstrated that gender was generally the best predictor of torque, and that all the torque measures were significantly correlated.

Abdominal Muscles↗
PubMed1994

Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q.

Breast cancer in men is about a hundredfold less common than in women and this has hindered research into its genetic basis. We have examined 22 families with at least one case of male breast cancer for linkage to the hereditary breast and ovarian cancer locus, BRCA1, on chromosome 17q. We found strong evidence against linkage to BRCA1 (lod score-16.63) and the best estimate of the proportion of linked families was 0% (95% CI 0-18%). Our results indicate that there is a gene(s) other than BRCA1 which predisposes to early-onset breast cancer in women and which confers a higher risk of male breast cancer. Identification of additional pedigrees that include cases of male breast cancer may therefore facilitate the mapping and isolation of this gene.

Breast Neoplasms↗
PubMed1994

FPTT is a low-incidence Rh antigen associated with a "new" partial Rh D phenotype, DFR.

BACKGROUND: Several Rh D phenotypes with partial D antigens are recognized. Some partial D antigens are associated with low-incidence Rh antigens. New partial D antigens are revealed by an atypical pattern of reactions with anti-D. STUDY DESIGN AND METHODS: The reactions of D variant cells with panels of monoclonal anti-D and with antibodies to low-incidence antigens were compared to those of known D categories to identify a new Rh D phenotype. The inheritance of partial D antigens was studied by Rh phenotyping of the families of the probands. Standard serologic methods were used and family data were analyzed. RESULTS: A new Rh D phenotype, to be called DFR, was identified in 17 probands, two of whom had made anti-D. The partial D antigen carries epD3, epD4, and epD9 and lacks epD8. The presence of other D epitopes is ambiguous; different answers were obtained for the same sample with different monoclonal anti-D of the same apparent epitope specificity. The immunoglobulin class of the anti-D was important: IgG were more successful than IgM monoclonal anti-D in detecting the partial D of DFR. Family studies showed that DFR traveled with Ce more frequently than with cE. The low-incidence antigen FPTT (International Society of Blood Transfusion number 700048) was found on all DFR samples. Family studies demonstrated that FPTT is, as suspected, part of the complex Rh system. CONCLUSION: The partial D of the Rh D phenotype, DFR, is recognized by its pattern of reactions with monoclonal anti-D and its association with the low-incidence antigen FPTT, FPTT has now been numbered Rh50.

Antibodies, Monoclonal↗
PubMed1994

Allogeneic and autologous bone marrow transplantation for acute non-lymphoblastic leukaemia.

Bone marrow transplantation (BMT) has had an increasing role in the treatment of acute nonlymphoblastic leukaemia (ANLL). A review of patients transplanted between May 1975 and August 1991 was undertaken in order to evaluate problems and outcome, and examine the role of both autologous and allogeneic BMT at various stages in the treatment of ANLL. Forty-seven patients received either an allogeneic (n = 24) if a suitable donor was identified or autologous (n = 23) BMT if there was no allogeneic donor. Conditioning therapy consisted of total body irradiation (TBI) and cyclophosphamide (n = 14) or busulfan and cyclophosphamide (n = 33) with or without melphalan. Graft-versus-host disease prevention was with methotrexate (n = 9), methotrexate and cyclosporin (n = 10) or T cell depletion (n = 5). Minimum follow-up for surviving patients was 24 months (median 65 months). For patients transplanted in first remission there was a 0% and 9 +/- 6% transplant-related mortality, a 37 +/- 11% and 33 +/- 12% relapse risk and a 63 +/- 11% and 63 +/- 12% event-free survival for autologous and allogeneic BMT, respectively. In second remission, there was a 14% mortality, 50 +/- 20% relapse risk and 43 +/- 19% event-free survival for allogeneic BMT. No patient transplanted in relapse survived. In patients who survived greater than 24 months, late side effects were noted in all 8 (100%) patients given TBI and in 2 of 19 (10.5%) given busulfan.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

HLA non-identical T-cell-depleted bone marrow transplantation for primary immunodeficiency diseases.

BACKGROUND: Bone marrow transplantation (BMT) is usually the only procedure offering cure for children with life-threatening immune deficiency disorders, but compatible sibling donors are frequently unavailable. AIMS AND METHODS: To examine the outcome of HLA non-identical T-cell-depleted BMT carried out between April 1985 and May 1992 in 11 patients with primary immunodeficiency diseases and to seek prognostic factors. RESULTS: Eight patients achieved sustained engraftment, one after a second BMT. One further patient engrafted transiently, but rejected the graft five months later. Acute graft-versus-host disease (GVHD) grade II was seen in one and chronic GVHD was seen in three children. Seven patients survived beyond six months, six with donor T cell and five with donor B cell engraftment. At present, five patients (46%) are alive with immune reconstitution at a median follow-up of 14 months (range 6 to 78 months). The major factor associated with outcome was the presence of any infection within one week of BMT (p = 0.01). The presence of lung infection also tended to be a poor prognostic factor (p = 0.06) but did not reach significance, presumably because of the small sample size. HLA non-identical (parental) T-cell depleted BMT plays an important role in the cure of children with immunodeficiencies who do not have an identical sibling donor. Survival can be further improved if the diagnosis of immunodeficiency disease is made early and BMT undertaken before significant infections occur. CONCLUSIONS: The availability of T-cell depleted haploidentical parental bone marrow transplant can be anticipated to improve outcome significantly for children with severe immunodeficiency, especially when diagnosed early.

Bone Marrow Transplantation↗
PubMed1994

Look After Your Heart programme: impact on health status, exercise knowledge, attitudes, and behaviour of retired women in England.

OBJECTIVES: To evaluate the impact of the Health Education Authority's 20 hour Look After Your Heart health promotion course on a large group of retired women. DESIGN: Three groups of retired women were compared: group 1 women, drawn from 12 retirement groups, participated in the programme; group 2, drawn randomly from the same groups, declined; group 3, selected randomly from 12 different retirement groups matched for geographical area, were not offered the course. SETTING: Twenty four retirement groups established by a major national retail company in England. SUBJECTS: A total of 739 women with a mean age of 66 years participated. Altogether 200 women were in group 1, 192 in group 2, and 347 in group 3. MAIN OUTCOME MEASURE: The Nottingham Health Profile was administered and exercise knowledge, attitudes, and behaviour of the three groups were assessed using a validated, reliable questionnaire. RESULTS: Group 1 had significantly better self-perceived health, indicated by lower Nottingham Health Profile scores, more exercise knowledge, and positive exercise attitudes and they did more exercise than the other two groups. The responses of groups 2 and 3 were similar. Time since completion of the programme did not have any effect on Nottingham Health Profile scores, exercise knowledge, and behaviour. CONCLUSION: The Look After Your Heart programme is associated with beneficial and persistent effects in retired women. Detailed studies are needed to confirm whether these associations are due to the programme or reflect the selection of fitter, healthier subjects.

Aged↗
PubMed1994

Genetic mapping of the FACC gene and linkage analysis in Fanconi anaemia families.

Fanconi anaemia is an autosomal recessive disorder associated with increased chromosome breakage and progressive bone marrow failure. The gene for complementation group C (FACC) has been cloned and mapped to chromosome 9q22.3, but neither its genetic location nor the proportion of patients belonging to group C is known. We have used a polymorphism within the FACC gene to localise it within a 5 cM interval on chromosome 9q, bounded by D9S196/D9S197 and D9S176. The genes for Gorlin's syndrome and multiple self-healing squamous epitheliomata have also been mapped to this interval. Linkage analysis with the three highly informative microsatellite polymorphisms flanking FACC in 36 Fanconi anaemia families showed that only 8% of families were linked to this locus. This indicates that the genes for the other Fanconi anaemia complementation groups must map to one or more different chromosomal locations. The markers also allowed rapid exclusion of 56% of the families in our panel from complementation group C, thus substantially reducing the number of patients who need to be screened for FACC mutations.

Chromosome Mapping↗