Role of contrast-enhanced ultrasound in the evaluation of post-liver transplant vasculature.

Liver transplantation is a frequently used treatment for patients with end-stage liver disease and ultrasound is often the first-line imaging technique for detection of vascular complications after liver transplant. Although colour Doppler ultrasound is a good screening method for evaluation of post-liver transplant vasculature, it has limitations in evaluating small-calibre vessels and vessels in close proximity. Contrast-enhanced ultrasound (CEUS) has been proposed to overcome these limitations by improving visualisation of post-liver transplant vasculature and reducing the number of false-positive cases, which necessitate unnecessary additional investigations such as computed tomography or angiography. Liver transplant anatomy and the wide array of post-transplant imaging findings on colour Doppler have already been well described but literature on the use of CEUS and its image interpretation remain scarce. This review aims to discuss the indications for CEUS after liver transplant, to demonstrate CEUS technique and familiarise readers with the imaging appearances of post-transplant vascular complications on CEUS.

Identification of genetic risk associated with prostate cancer using ancestry informative markers.

BACKGROUND: Prostate cancer (PCa) is a common malignancy and a leading cause of cancer death among men in the United States with African-American (AA) men having the highest incidence and mortality rates. Given recent results from admixture mapping and genome-wide association studies for PCa in AA men, it is clear that many risk alleles are enriched in men with West African genetic ancestry. METHODS: A total of 77 ancestry informative markers (AIMs) within surrounding candidate gene regions were genotyped and haplotyped using Pyrosequencing in 358 unrelated men enrolled in a PCa genetic association study at the Howard University Hospital between 2000 and 2004. Sequence analysis of promoter region single-nucleotide polymorphisms (SNPs) to evaluate disruption of transcription factor-binding sites was conducted using in silico methods. RESULTS: Eight AIMs were significantly associated with PCa risk after adjusting for age and West African ancestry. SNP rs1993973 (intervening sequences) had the strongest association with PCa using the log-additive genetic model (P=0.002). SNPs rs1561131 (genotypic, P=0.007), rs1963562 (dominant, P=0.01) and rs615382 (recessive, P=0.009) remained highly significant after adjusting for both age and ancestry. We also tested the independent effect of each significantly associated SNP and rs1561131 (P=0.04) and rs1963562 (P=0.04) remained significantly associated with PCa development. After multiple comparisons testing using the false discovery rate, rs1993973 remained significant. Analysis of the rs156113-, rs1963562-rs615382l and rs1993973-rs585224 haplotypes revealed that the least frequently found haplotypes in this population were significantly associated with a decreased risk of PCa (P=0.032 and 0.0017, respectively). CONCLUSIONS: The approach for SNP selection utilized herein showed that AIMs may not only leverage increased linkage disequilibrium in populations to identify risk and protective alleles, but may also be informative in dissecting the biology of PCa and other health disparities.

p53 Pro72Arg polymorphism and prostate cancer in men of African descent.

BACKGROUND: p53 is a transcription factor that regulates the cell cycle, DNA repair, and apoptosis. A variant at codon 72, rs1042522, results in altered activities for p53 and is, notably, differentially distributed among different ethnic populations. However, associations of this variant with cancer in men of African descent have not been explored. Herein, we tested the hypothesis that rs1042522 was associated with prostate cancer (PCa) risk. MATERIALS AND METHODS: Genotypes were determined by PCR-RFLP methods in a study population of African descent consisting of 266 PCa patients and 196 male controls. RESULTS: Our results indicate that the p53 polymorphism may be associated with increased risk of PCa. Genotypes were significantly and marginally associated with PCa risk using the dominant and log-additive genetic models (OR=1.53, 95% CI: 1.02-2.29, P=0.04; OR=1.33, 95% CI: 0.99-1.78, P=0.06, respectively). After adjusting for age, the associations with PCa remained, but results were not statistically significant (OR=1.48, 95% CI: 0.95-2.31, P=0.08; OR=1.30, 95% CI: 0.95-1.80, P=0.10, respectively). CONCLUSIONS: The present study demonstrates that population-dependent differences in allele frequencies associated with health disparities provide a valuable framework for the interrogation of complex diseases in all populations.

Steatosis predicts postoperative morbidity following hepatic resection for colorectal metastasis.

BACKGROUND: Few studies are available on the effect of steatosis on perioperative outcome following hepatic resection for colorectal liver metastasis (CRLM). METHODS: Patients undergoing resection for CRLM from January 2000 to September 2005 were identified from a hepatobiliary database. Data analysed included laboratory measurements, extent of hepatic resection, blood transfusion requirements and steatosis. RESULTS: There were 386 patients with a median age of 66 (range 32-87) years, of whom 201 had at least one co-morbid condition and 194 had an American Society of Anesthesiologists grade of I. Anatomical resection was performed in 279 patients and non-anatomical resection in 107; 165 had additional procedures. Steatosis in 194 patients was classified as mild in 122, moderate in 60 and severe in 12. The overall morbidity rate was 36 per cent (139 patients) and the mortality rate was 1.8 per cent (seven patients). Admission to the intensive care unit, morbidity, infective complications and biochemical profile changes were associated with greater severity of steatosis. Independent predictors of morbidity were steatosis, extent of hepatic resection and blood transfusion. CONCLUSION: Steatosis is associated with increased morbidity following hepatic resection. Other predictors of outcome were extent of hepatic resection and blood transfusion.

Conceptualizing human variation.

What is the relationship between the patterns of biological and sociocultural variation in extant humans? Is this relationship accurately described, or best explained, by the term 'race' and the schema of 'racial' classification? What is the relationship between 'race', genetics and the demographic groups of society? Can extant humans be categorized into units that can scientifically be called 'races'? These questions underlie the discussions that address the explanations for the observed differences in many domains between named demographic groups across societies. These domains include disease incidence and prevalence and other variables studied by biologists and social scientists. Here, we offer a perspective on understanding human variation by exploring the meaning and use of the term 'race' and its relationship to a range of data. The quest is for a more useful approach with which to understand human biological variation, one that may provide better research designs and inform public policy.

The radial and posterior interosseous nerves. Results fo 260 repairs.

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.

In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study.

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.

Tree-based linkage and association analyses of asthma.

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.

The musculocutaneous nerve.

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.

Use of classification trees for association studies.

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.

Obesity differences between African-American men and women.

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.

Ascertainment corrections based on smaller family units.

Ascertainment concerns the manner by which families are selected for genetic analysis and how to correct for it in likelihood models. Because such families are often neither drawn at random nor selected according to well-defined rules, the problem of ascertainment correction in the genetic analysis of family data has proved durable. This paper undertakes a systematic study of ascertainment corrections in terms of smaller distinct units, which will usually be sibships, nuclear families, or small pedigrees. Three principal results are presented. The first is that ascertainment corrections in likelihood models for family data can be made in terms of smaller units, without breaking up the pedigree. The second is that the appropriate correction for single ascertainment in a unit is the reciprocal of the sum of the marginal probabilities of all the persons relevant to its ascertainment, as if affected. The third result is a generalization of the single ascertainment-correction formula to k-plex ascertainment, in which each unit has k or more affecteds. The correction is the reciprocal of the sum of the joint probabilities of all distinct sets of k persons in the unit, as if they were all affected. In extended families, two additional ascertainment schemes will be considered and explicit formulas will be presented. One of these schemes is "uniform-proband-status ascertainment," in which nonmembers of a given unit have the same chance as members to become probands if they are affected; the other scheme is the "inverse law of ascertainment," in which the chance that nonmembers of a unit will become probands for that unit decreases with degree of relationship. Several specific recommendations are made for further study.

Strategies to encourage mammography use among women in senior citizens' housing facilities.

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.

Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk.

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.

The relationship of body mass index to reproductive factors in pre- and postmenopausal African-American women with and without breast cancer.

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.

BRCA1 testing in families with hereditary breast-ovarian cancer. A prospective study of patient decision making and outcomes.

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.

Reaching midlife and older smokers: tailored interventions for routine medical care.

BACKGROUND: Although older adults can achieve significant health benefits from smoking cessation, few programs have specifically targeted this population. This study tested the effectiveness of an office-based smoking cessation program tailored to midlife and older smokers. METHODS: This paper describes a randomized controlled trial comparing usual care with physician-delivered brief quit-smoking advice and counseling for midlife and older smokers (ages 50-74). Outpatient medical practices assigned to the Immediate Intervention (experimental) condition were trained to deliver brief quit-smoking advice and counseling. Delayed Intervention (control) practices followed usual care procedures. Thirty-nine practices accruing five or more patients per practice were included in the analyses. RESULTS: Using conservative measure of quitting, self-reported quit rates at 6-month follow-up were 15.41% for the Immediate Intervention group versus 8.16% of subjects in the Delayed Intervention group (P < 0.005). Baseline subject (N = 659) characteristics related to 6-month abstinence included number of previous quit attempts, quitting for 24 hr in the past year, desire to quit, confidence in quitting, perceived health benefits, and lower nicotine dependence. CONCLUSIONS: Smoking abstinence was significantly increased by training physicians and key office and clinical staff to intervene with older smokers. Brief interventions are tailored to this age cohort can be successfully and efficaciously integrated into routine care.