Biomedical subjects
Publications and source records attributed to G Bonney.
Tree-based linkage analyses and association studies are introduced and applied for two data sets on asthma from Genetic Analysis Workshop 12. Consistent and strong evidence of linkage and association to markers on chromosomes 1 and 11 is revealed. Linkage to chromosome 16 in one data set and association with D6S276 in the other data set are also detected.
PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.
The outcome of 260 repairs of the radial and posterior interosseous nerves, graded by Seddon's modification of the Medical Research Council Special Committee's system, was analysed according to four patterns of injury; open 'tidy', open 'untidy', closed traction, and those associated with injury to the axillary or brachial artery. We studied the effect on the outcome of delay in effecting repair and of the length of the defect in the nerve trunk. Of the 242 repairs of the radial nerve we found that 30% had good results and 28% fair; 42% of the repairs had failed. The violence of injury was the most important factor in determining the outcome. Of the open 'tidy' repairs, 79% achieved a good or fair result, and 36% of cases with arterial injury also reached this level. Most repairs failed when the defect in the nerve trunk exceeded 10 cm. When the repairs were carried out within 14 days of injury, 49% achieved a good result; only 28% of later repairs did so. All repairs undertaken after 12 months failed. Of the 18 repairs of the posterior interosseous nerve, 16 achieved a good result.
We propose the use of classification trees for association studies. This approach is applied to a data set from Genetic Analysis Workshop 9 (GAW9), and our analysis precisely identified two disease alleles. Our purpose is to demonstrate the great potential of tree-based analyses for genetic studies, and discuss some issues that warrant further investigation.
We have analysed the results of repair of traumatic lesions of the musculocutaneous nerve in 85 patients, which were graded by Seddon's modification of the Medical Research Council system into three types of injury: open 'tidy', open 'untidy' and closed 'traction'. They were also correlated with associated arterial injury. There were 57 good, 17 fair and 11 poor results. The type of injury was the most important factor in determining the result; 12 of 13 open-tidy lesions gave good results compared with 30 of 48 closed-traction lesions. The results were better when the nerves were repaired within 14 days of injury and when grafts were less than 10 cm long. They were worse in the presence of associated arterial or bony injury.
The purpose of this study was to examine the socio-demographic and behavioral differences related to obesity between African-American men and women. Obesity was defined as a body mass index of greater than 27.3 kg/m2 for women and 27.8 kg/m2 for men. Data were collected from 661 African-Americans, 418 women and 243 men, residing in wards 7 and 8 in Washington, DC through telephone interviews. Obesity was prevalent among 38.3% of the women and 20.1% of the men (p < 0.01). For women age 55 or older, annual income over $20K, having less than a high school education, and alcohol and tobacco consumption were associated with being overweight in the initial bivariate analysis (p < 0.05). For men, being 35 years or older and unemployment were significant factors associated with obesity. Our final analysis, when known dietary risk factors were adjusted, revealed that in women, obesity was associated with age, hard liquor consumption and non use of tobacco. For men, older age was a primary association. We concluded that gender, with increasing age, plays a significant role in predicting obesity, as defined by concurrent national standards. African American men 55 years of age or older are the most likely group to be overweight even after predisposing and behavioral risk factors are considered.
BACKGROUND: This randomized trial evaluated the impact of mammography-enhancing interventions implemented in 40 senior citizens' housing facilities in Pennsylvania and North Carolina. METHODS: After stratification of the facilities according to the socioeconomic status and racial backgrounds of their residents, they were randomly assigned to one of four groups to receive the following: 1) standard care--a Medicare mammography benefit flier; 2) education--the flier and a community education program; 3) access--the flier, mammography appointments, and transportation; 4) combined--all interventions. Telephone surveys, conducted prior to any intervention, identified mammography-eligible women, who were re-surveyed six months later to ascertain mammography use. RESULTS: Logistic regression analyses identified mammography intention, age, and the interaction between ever having had mammography and being in the combined intervention group to be significant predictors of mammography use at six months. However, no significant main effect was found for any of the interventions. CONCLUSIONS: These results suggest that the combination of community-directed mammography education and access to mammography appointments encourages mammography use primarily by women who are already predisposed to having mammography. However, individually targeted and tailored interventions may be needed to encourage mammography use among women who have never had mammography and/or express no intention of having it done.
OBJECTIVES: To identify predictors of utilization of breast-ovarian cancer susceptibility (BRCA1 gene) testing and to evaluate outcomes of participation in a testing program. DESIGN: Prospective cohort study with baseline interview assessment of predictor variables (eg, sociodemographic factors, knowledge about hereditary cancer and genetic testing, perceptions of testing benefits, limitations, and risks). BRCA1 test results were offered after an education and counseling session in a research setting. Outcome variables (including depression, functional health status, and prophylactic surgery plans [follow-up only]) were assessed at baseline and 1-month follow-up interviews. PARTICIPANTS: Adult male and female members (n=279) of families with BRCA1-linked hereditary breast-ovarian cancer (HBOC). RESULTS: Of subjects who completed a baseline interview (n=192), 60% requested BRCA1 test results (43% of all study subjects requested results). Requests for results were more frequent for persons with health insurance (odds ration [OR], 3.74; 95% confidence interval [CI], 2.06-6.80); more first-degree relatives affected with breast cancer (OR, 1.59; 95% CI, 1.16-2.16); more knowledge about BRCA1 testing (OR, 1.85; 95% CI, 1.36-2.50); and indicating that test benefits are important (OR, 1.45; 95% CI, 1.13-1.86). At follow-up, noncarriers of BRCA1 mutations showed statistically significant reductions in depressive symptoms and functional impairment compared with carriers and nontested individuals. Individuals identified as mutation carriers did not exhibit increases in depression and functional impairment. Among unaffected women with no prior prophylactic surgery, 17% of carriers (2/12) intended to have mastectomies and 33% (4/12) to have oophorectomies. CONCLUSIONS: Only a subset of HBOC family members are likely to request BRCA1 testing when available. Rates of test use may be higher in persons of a higher socioeconomic status and those with more relatives affected with breast cancer. For some high-risk individuals who receive test results in a research setting that includes counseling, there may be psychological benefits. More research is needed to assess the generalizability of these results and evaluate the long-term consequences of BRCA1 testing.
To date, there are virtually no existing data on the relationship between obesity, menopausal status, and breast cancer in African-Americans. Therefore, the present study was designed to test the following hypotheses in an African-American population: (1) there exists a positive association between BMI and breast cancer among postmenopausal women; (2) there exists an inverse association between BMI and breast cancer among premenopausal women; and (3) similar associations between BMI and reproductive factors exist for both pre- and postmenopausal breast cancer cases. The study population comprised 357 African-American women (n = 193 breast cancer cases; n = 164 controls). No significant differences were observed between premenopausal cases and controls for BMI, obesity categories, and reproductive factors. Among the postmenopausal women, the cases had significantly lower weight and BMI levels than the controls. Age at first pregnancy and parity were significantly lower among postmenopausal cases than their controls. No significant associations were revealed between body mass index and breast cancer for pre- and postmenopausal women. In the present study, early age at menarche was the only reproductive factor that was an independent predictor of BMI for both pre- and postmenopausal women, irrespective of breast cancer status. Also, these findings strongly suggest the need to consider reproductive factors, particularly age at menarche, as a covariate of BMI and other obesity-related diseases.
Despite the fact that breast cancer is the most common non-cutaneous cancer and a leading cause of cancer deaths in women, accepted markers of breast cancer risk miss up to 40% of these tumors. Moreover, screening methods involving the analysis of tissue or cells are limited by the need for a surgical biopsy. Nipple aspiration is a quick, efficient, noninvasive method to obtain breast epithelial cells, the cells at risk for transformation to carcinoma. Prostate-specific antigen (PSA), a protein thought to be specific to the prostate but recently found in a subset of breast tumors, has been correlated with improved survival. The purpose of this study was to measure PSA in a group of women with increasing breast cancer risk (no risk or family history of breast cancer, precancerous mastopathy, and invasive cancer) and determine if PSA correlates with risk. Nipple aspirate fluid was obtained from the intact breast and from surgical specimens using a modified breast pump. PSA was then measured in the fluid using a highly sensitive and specific immunofluorometric procedure. PSA was found at levels ranging from 0-13,423 ng/g of total protein, and there was a significant relationship between PSA level and breast cancer risk (P = 0.001). That is, all women with no risk factors and 90% of those with a family history had high PSA levels, whereas 68% of subjects with precancerous mastopathy or invasive cancer had low PSA levels. PSA was higher in premenopausal subjects (P = 0.002). After adjusting for the effect of menopausal status, there remained a significant association between PSA and breast cancer risk. These findings suggest that PSA in nipple aspirate fluid may be a useful marker of breast cancer risk.
A telephone survey of knowledge, attitude, and health practices regarding cancer was undertaken in wards 7 and 8, Washington, DC in 1988. These wards have the highest cancer rates in the city and are predominantly African American. Of the 670 randomly selected persons over 18 years of age, 243 were males and 427 were females. Among females, 84% believed cigarette smoking causes cancer, and 48% thought alcohol causes cancer; 31% smoked cigarettes and 38% consumed alcoholic beverages. Among males, 91% and 52% thought cigarettes and alcohol causes cancer respectively; 41% smoked and 54% consumed alcoholic beverages. Only 6% of the males over age 40 practiced all eight recommended cancer prevention behaviors, while 2% of the females over age 40 practiced all preventive health behaviors. Cancer preventive behavior was examined in relation to socioeconomic status. This study indicates that preventive health behaviors were not associated with socioeconomic status. Data suggest that cancer prevention and control programs and services targeted to this Washington, DC population should be increased and intensified.
Amputation of the upper limb was performed in 20 out of 750 patients with traction lesions of the brachial plexus between August 1969 and June 1991. Urgent amputation was necessary in three patients with irreparable vascular injury and in two more because of overwhelming sepsis. Thirteen patients chose amputation of their flail and useless arm. Two patients have been lost to follow-up. Urgent amputation is indicated when perfusion of the limb cannot be restored, for sepsis, and for a limb which is so severely injured that there can be no prospect for a return of any function. Elective amputation is performed at the patient's request and may be considered as an element of rehabilitation. The pain of preganglionic injury of the brachial plexus is not relieved by amputation.
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This article describes breast cancer cases seen at the Howard University Hospital from 1960 through 1987 using information from the database of the Tumor Registry, established in 1960. Clinical information at presentation is presented as well as a description of reproductive and demographic characteristics. Pre- and postmenopausal women are compared, revealing differences in reproductive experience. This may contribute to the increasing incidence of breast cancer seen among younger women in recent years. This is of particular interest because the classic excess of nulliparous women among breast cancer cases is not seen among the population described here.
Five patients with unresectable pancreatic adenocarcinoma were treated with simultaneous intraoperative radiotherapy and intraoperative hyperthermia. Postoperative survivorship averaged 15.8 months, which compares favorably to a previous study in which 19 patients receiving intraoperative radiotherapy without intraoperative hyperthermia survived an average of 6.05 months. Three of the five patients following the experimental protocol of intraoperative radiotherapy and intraoperative hyperthermia with additional external beam radiotherapy are still alive, which may result in average postoperative survivorship exceeding 15.8 months.
In this study, we discuss 68 cases in which peripheral nerve trunks were inadvertently divided by surgeons. Most of these accidents occurred in the course of planned operations. Delay in diagnosis and in effecting repair was common. We list the nerves particularly at risk and the operations in which special care is needed. We recommend steps to secure prompt diagnosis and early treatment.
The nuclear enzyme poly(ADP-ribose) polymerase (PADPRP) is thought to play a role in DNA recombination, replication, and repair. In view of the implication of these processes in tumorigenesis, and based on preliminary evidence which indicated the presence of an extraneous polymorphic restriction fragment for murine PADPRP loci in strains of mice susceptible to plasmacytomas, we investigated correlations between the restriction fragment length polymorphism of the PADPRP gene(s) and human Burkitt lymphoma. No increase in the frequency of polymorphisms on chromosome 1 (containing the active gene) or on chromosome 14 (a pseudogene) was observed. However, restriction fragment length polymorphism analysis of PADPRP sequences on chromosome 13 (either a processed pseudogene or a gene with extensive identity to PADPRP) revealed that of 19 DNA samples derived from endemic Burkitt lymphoma all contained at least one copy of a rare allele (B). Simple two-allele (A/B) polymorphisms in this PADPRP-like locus were identified by digestion with a number of restriction enzymes including HindIII, PstI, KpnI, and MspI. These restriction fragment length polymorphisms always segregated together, suggesting that they identify a deletion within or close to the PADPRP sequences on chromosome 13, which we mapped precisely to 13q33-qter. Based upon family studies the A and B alleles were shown to be transferred in a Mendelian codominant fashion. Subsequently, this probe was used as a linkage marker to study the frequency of this deletion in various tumors including B-cell follicular lymphomas, small cell lung carcinomas, breast carcinomas, and colorectal carcinomas. In noncancer control populations, the frequency of this deletion was 3-fold higher among Blacks as compared to Caucasians. When DNA from various tumors was compared to normal DNA from racially appropriate noncancer controls, the frequency of this deletion was still 2- to 3-fold higher in the tumor DNA. Matched samples provided instances of tumor-specific loss of heterozygosity but also revealed that the predominant source of this deletion is the germ line, suggesting that the chromosome 13 region neighboring the PADPRP locus may harbor a gene whose loss may predispose individuals to malignancy.