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Biomedical subjects

D Ford

Publications and source records attributed to D Ford.

At least 91 records · Page 5Linked to original sources
PubMed1994

Familial site-specific ovarian cancer is linked to BRCA1 on 17q12-21.

In a study of nine families with "site-specific" ovarian cancer (criterion: three or more cases of epithelial ovarian cancer and no cases of breast cancer diagnosed at age < 50 years) we have obtained evidence of linkage to the breast-ovarian cancer susceptibility gene, BRCA1 on 17q12-21. If the risk of cancer in these families is assumed to be restricted to the ovary, the best estimate of the proportion of families linked to BRCA1 is .78 (95% confidence interval .32-1.0). If predisposition to both breast and ovarian cancer is assumed, the proportion linked is 1.0 (95% confidence interval .46-1.0). The linkage of familial site-specific ovarian cancer to BRCA1 indicates the possibility of predictive testing in such families; however, this is only appropriate in families where the evidence for linkage to BRCA1 is conclusive.

BRCA1 Protein↗
PubMed1993

Absence of linkage to the ataxia telangiectasia locus in familial breast cancer.

Heterozygotes for ataxia-telangiectasia (AT) are known to have an increased risk of breast cancer. The gene (or genes) responsible for almost all cases of AT has been localised to chromosome 11q by genetic linkage analysis. To examine the possibility that AT heterozygosity may account for a substantial proportion of familial breast cancer, we have typed five markers on chromosome 11q in 16 breast cancer families. We have found no evidence for linkage between breast cancer and chromosome 11q markers and conclude that the contribution of AT to familial breast cancer is likely to be minimal.

Ataxia Telangiectasia↗
PubMed1993

Inherited susceptibility to breast cancer.

Four genes are now known to be responsible for inherited susceptibility to breast cancer: the BRCA1 gene on chromosome 17q21, the ataxia-telangiectasia (AT) gene (11q22-q23), the TP53 gene (17p13.1) and the androgen receptor (AR) (Xq11.2-q12). These genes, however, differ dramatically in terms of the risk of breast cancer that they confer, the proportion of breast cancer incidence that they account for and the other cancers and other phenotypes with which they are associated. Genetic linkage studies have shown that some high risk breast cancer families, particularly those where breast cancer occurs in association with ovarian cancer, are due to a gene on chromosome 17q known as BRCA1. The BRCA1 gene is estimated to confer a breast cancer risk of about 70% by age 70, and may account for about 2% of overall breast cancer incidence, although a higher proportion of younger cases. Germline mutations in the TP53 gene are responsible for a high proportion of LI-Fraumeni families, in which breast cancer occurs in association with childhood sarcomas and other cancers. In such families, the risk of breast cancer is over 50% by age 50, and the risk of all cancers is nearly 100%; germline TP53 mutations are, however, probably responsible for much less than 1% of all breast cancer. By contrast, heterozygotes for the AT gene carry a much more moderate risk of breast cancer. This gene, however, is much more common in the population and may account for 7% or more of breast cancer incidence. Finally, germline mutations in the androgen receptor are known to cause male breast cancer, but this has only been demonstrated in two families. Evidence from linkage and population based studies suggests that these genes may account for about one half of the observed familial clustering of breast cancer; other breast cancer susceptibility genes therefore remain to be identified.

Aged↗
PubMed1993

c-fms point mutations in acute myeloid leukemia: fact or fiction?

Point mutations in codons 12, 13, and 61 of N-ras have consistently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) using a variety of techniques. Recently mutations in codons 301 and 969 of c-fms, preferentially involving TAT-to-TGT at codon 969, have also been identified in these disorders by allele specific oligonucleotide (ASO) hybridization. We have developed allele specific restriction analysis (ASRA) protocols for the detection of point mutations in the critical codons of these genes. ASRA involves enzymatic digestion of polymerase chain reaction (PCR)-induced restriction sites which are specific for normal but not mutant alleles. A total of 11 N-ras mutations were observed in 10 out of 46 AML patients, consistent with the reported frequency of N-ras mutations when alternative techniques of comparable sensitivity are used. In contrast, c-fms point mutations were not detected in a similar number of patients with AML, including 39 studied for mutations in both N-ras and c-fms, and this difference is statistically significant (p < 0.003). A more sensitive technique (ASRA + ASO hybridization) also failed to detect TAT-to-TGT substitutions at codon 969 in a subgroup of M4-AML patients considered to be at greatest risk of harboring c-fms mutations. This study suggests that c-fms mutations at codons 301 and 969 are not important in the pathogenesis of AML in the vast majority of patients.

Acute Disease↗
PubMed1993

Rate of marrow engraftment does not appear to be adversely affected by early marrow infusion after total body irradiation.

Bone marrow transplantation (BMT) provides a means of increasing chemo-radiotherapy doses beyond the limits imposed by marrow toxicity. The time interval between myeloablative therapy and marrow infusion needs to be optimized to ensure prompt engraftment. It has been suggested that early marrow infusion after completion of total body irradiation (TBI) may be detrimental to rapid marrow reconstitution. Hence a retrospective analysis of 75 BMT patients was performed to document the rate of marrow engraftment following marrow infusion given immediately after TBI. Engraftment rates (time to absolute neutrophil count to greater than 0.5 x 10(9)/L) of patients receiving different conditioning regimens were compared. Results show similar engraftment rates in patients receiving bone marrow infusion 27.7 and 32.1 hours after completion of chemotherapy in autologous (20.5 days) and allogeneic (18.5 days) transplants respectively, or 2.9 and 2.0 hours after completion of TBI in autologous (20.1 days) and allogeneic (19.4 days) transplants respectively. These results are similar to those reported for delayed marrow infusion after TBI and would support that early marrow infusion after TBI does not adversely influence rate of engraftment. Thus it appears appropriate to give marrow immediately after completion of TBI.

Bone Marrow↗
PubMed1993

Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium.

Breast cancer is known to have an inherited component, consistent in some families with autosomal dominant inheritance; in such families the disease often occurs in association with ovarian cancer. Previous genetic linkage studies have established that in some such families disease occurrence is linked to markers on chromosome 17q. This paper reports the results of a collaborative linkage study involving 214 breast cancer families, including 57 breast-ovarian cancer families; this represents almost all the known families with 17q linkage data. Six markers on 17q, spanning approximately 30 cM, were typed in the families. The aims of the study were to define more precisely the localization of the disease gene, the extent of genetic heterogeneity and the characteristics of linked families and to estimate the penetrance of the 17q gene. Under the assumption of no genetic heterogeneity, the strongest linkage evidence was obtained with D17S588 (maximum LOD score [Zmax] = 21.68 at female recombination fraction [theta f] = .13) and D17S579 (Zmax = 13.02 at theta f = .16). Multipoint linkage analysis allowing for genetic heterogeneity provided evidence that the predisposing gene lies between the markers D17S588 and D17S250, an interval whose genetic length is estimated to be 8.3 cM in males and 18.0 cM in females. This position was supported over other intervals by odds of 66:1. The location of the gene with respect to D17S579 could not be determined unequivocally. Under the genetic model used in the analysis, the best estimate of the proportion of linked breast-ovarian cancer families was 1.0 (lower LOD-1 limit 0.79). In contrast, there was significant evidence of genetic heterogeneity among the families without ovarian cancer, with an estimated 45% being linked. These results suggest that a gene(s) on chromosome 17q accounts for the majority of families in which both early-onset breast cancer and ovarian cancer occur but that other genes predisposing to breast cancer exist. By examining the fit of the linkage data to different penetrance functions, the cumulative risk associated with the 17q gene was estimated to be 59% by age 50 years and 82% by age 70 years. The corresponding estimates for the breast-ovary families were 67% and 76%, and those for the families without ovarian cancer were 49% and 90%; these penetrance functions did not differ significantly from one another.

Adult↗
PubMed1992

Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma.

OBJECTIVE: To assess the risk of second brain tumour in patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. DESIGN: Long term follow up of a cohort of patients with pituitary adenoma and comparison of tumour occurrence with population incidence rates. SETTING: The Royal Marsden Hospital. SUBJECTS: 334 patients with pituitary adenoma treated with conservative surgery and radiotherapy (median dose 45 Gy) and followed up for 3760 person years. MAIN OUTCOME MEASURES: Second intracranial tumour and systemic malignancy. RESULTS: Five patients developed a second brain tumour: two had astrocytoma, two meningioma, and one meningeal sarcoma. The cumulative risk of developing a second brain tumour over the first 10 years after treatment was 1.3% (95% confidence interval 0.4% to 3.9%) and over 20 years 1.9% (0.7% to 5.0%). The relative risk of a second brain tumour compared with the incidence in the normal population was 9.38 (3.05 to 21.89). There was no excess risk of any other type of second primary malignancy. CONCLUSIONS: There is an increased risk of second intracranial tumour in patients with pituitary adenoma treated with surgery and radiotherapy. Although radiation is likely to be the most important factor contributing to the excess risk, further study is required in a cohort of similar patients not receiving radiation.

Adenoma↗
PubMed1992

Health of the public. The academic response. Health of the Public Mission Statement Working Group.

Aging of the population, increasing prevalence of chronic and disabling illnesses with multiple social and behavioral risk factors, concern about quality of care, and escalating costs of medical care require fundamental changes in the way that academic health centers discharge their mission. This article describes a newly developed "Mission Statement" for academic health centers that wish to contribute positively to the health of the populations that they serve. A shift toward addressing the needs of the public may produce increasing institutional strength, long-run stability, and enhanced productivity, as well as higher quality, more cost-effective care for patients. Seventeen centers in the Health of the Public Program are currently conducting activities that implement the described mission elements. The goals and objectives described herein create a foundation for change, with more balanced institutional goals, and could turn an emerging confrontation between academe and its public into an opportunity for both.

Academic Medical Centers↗
PubMed1992

Can health visitors prevent fractures in elderly people?

OBJECTIVES: To assess whether intervention by a health visitor could reduce the number of fractures, over a four year period, in those aged 70 and over. DESIGN: Randomised, controlled trial; randomisation by household. SETTING: General practice in a market town. SUBJECTS: Of 863 patients aged 70 and over on the practice records, 674 were traced and successfully interviewed; 350 were assigned to the intervention group, 324 as controls. INTERVENTION: The people in the intervention group were allocated to the care of a health visitor. The approach was four pronged: assessment and correction of nutritional deficiencies, including reducing smoking and alcohol intake; assessment and referral of medical conditions such as heart block or inappropriate medication; assessment and correction of environmental hazards in the home such as poor lighting; assessment and improvement of fitness--for example, exercise classes for the moderately fit. The intervention continued for four years. MAIN OUTCOME MEASURE: Fracture rate over four years. RESULTS: The incidence of fractures was 5% (16/350) in the intervention group and 4% (14/324) in the control group (difference not significant). CONCLUSIONS: A health visitor visiting a group of people aged 70 and over and using simple preventive measures had no effect on the incidence of fractures.

Aged↗
PubMed1992

Measurement of torque of trunk flexors at different velocities.

The purpose of this study was to determine the test-retest reliability of recording isometric and isokinetic torque of the trunk flexors and to examine the effect of velocity on the torque curves. Thirty healthy subjects were tested on two occasions for isometric torque of trunk flexion at four angles and eccentric and concentric torque at three velocities. Two subjects repeated these tests in the passive mode to determine the torque produced by the trunk when there was no active flexion effort. Intraclass correlation coefficients were above 0.85 for all isometric and isokinetic measures. Standard errors of measurement ranged from 6.9 to 19.5 Nm. Student t-tests indicated no significant differences between occasions for all outcome measures. Examination of passive and active torque curves indicated that the torque produced by the mass of the trunk increased with increasing velocity. It is concluded that both isometric and isokinetic testing of the trunk flexors are reliable, but that testing at higher velocities may not provide a valid measure of muscle performance.

Abdominal Muscles↗
PubMed1990

Bone marrow transplantation for childhood acute lymphoblastic leukaemia after marrow relapse.

Children with acute lymphoblastic leukaemia in whom relapse in bone marrow occurs have a poor outlook when treated with chemotherapy alone. Twenty-seven patients with childhood acute lymphoblastic leukaemia were treated for marrow relapse with high-dose chemotherapy with or without total body irradiation followed by bone marrow transplantation (BMT). Twenty patients received allogeneic marrow from partially or completely matched histocompatible donors. In this group, nine patients (45%) were free of disease with a median follow-up of 57 months (range, 22 to 126 months) after transplantation, four (20%) died from interstitial pneumonitis and seven (35%) died after a further relapse. Seven patients received autologous marrow collected while they were in remission. In this group, one patient died from infection and six died after a further relapse. We conclude that allogeneic BMT is more effective than autologous transplantation and results in long-term disease-free survival in a significant number of patients. New methods are needed to eradicate residual disease in the patient and to purge marrow ex vivo.

Actuarial Analysis↗
PubMed1990

Angina among elderly people and its relationship with disability.

A postal questionnaire was sent to 2705 people aged 60 and over requesting information about anginal symptoms, their degree of disability and dependency and the use they made of community services. Those with angina showed marked degrees of disability and dependency and used some services to a considerable extent. Postal questionnaires are a satisfactory screening device for identifying individuals at risk and can assist practitioners in organizing their workload for patients with disabling conditions.

Activities of Daily Living↗