Decisions and ethical issues among BRCA carriers and the use of preimplantation genetic diagnosis.

The lifetime risks for both breast and ovarian cancer for BRCA mutation carriers far exceeds the general population risk of 13% for breast cancer and 1.4% for ovarian cancer. BRCA carriers have unique and medically complicated decisions to make regarding their cancer treatment or risk reduction. As BRCA testing becomes increasingly common among unaffected individuals in families with a previously documented BRCA mutation, there are a growing number of individuals with unique psychosocial needs and concerns. This review paper describes the BRCA 1/2 population, discusses preimplantation genetic diagnosis (PGD), and describes the decisions and ethical issues related to PGD among the BRCA 1/ 2 population.

Growth hormone improves body composition, fasting blood glucose, glucose tolerance and liver triacylglycerol in a mouse model of diet-induced obesity and type 2 diabetes.

AIMS/HYPOTHESIS: Growth hormone has been used experimentally in two studies to treat individuals with type 2 diabetes, with both reporting beneficial effects on glucose metabolism. However, concerns over potential diabetogenic actions of growth hormone complicate its anticipated use to treat type 2 diabetes. Thus, an animal model of type 2 diabetes could help evaluate the effects of growth hormone for treating this condition. METHODS: Male C57BL/6J mice were placed on a high-fat diet to induce obesity and type 2 diabetes. Starting at 16 weeks of age, mice were treated once daily for 6 weeks with one of four different doses of growth hormone. Body weight, body composition, fasting blood glucose, insulin, glucose tolerance, liver triacylglycerol, tissue weights and blood chemistries were determined. RESULTS: Body composition measurements revealed a dose-dependent decrease in fat and an increase in lean mass. Analysis of fat loss by depot revealed that subcutaneous and mesenteric fat was the most sensitive to growth hormone treatment. In addition, growth hormone treatment resulted in improvement in glucose metabolism, with the highest dose normalising glucose, glucose tolerance and liver triacylglycerol. In contrast, insulin levels were not altered by the treatment, nor did organ weights change. However, fasting plasma leptin and resistin were significantly decreased after growth hormone treatment. CONCLUSIONS/INTERPRETATION: Growth hormone therapy improves glucose metabolism in this mouse model of obesity and type 2 diabetes, providing a means to explore the molecular mechanism(s) of this treatment.

The use of proteomics to study infectious diseases.

Technology surrounding genomics, or the study of an organism's genome and its gene use, has advanced rapidly resulting in an abundance of readily available genomic data. Although genomics is extremely valuable, proteins are ultimately responsible for controlling most aspects of cellular function. The field of proteomics, or the study of the full array of proteins produced by an organism, has become the premier arena for the identification and characterization of proteins. Yet the task of characterizing a proteomic profile is more complex, in part because many unique proteins can be produced by the same gene product and because proteins have more diverse chemical structures making sequencing and identification more difficult. Proteomic profiles of a particular organism, tissue or cell are influenced by a variety of environmental stimuli, including those brought on by infectious disease. The intent of this review is to highlight applications of proteomics used in the study of pathogenesis, etiology and pathology of infectious disorders. While many infectious agents have been the target of proteomic studies, this review will focus on those infectious diseases which rank among the highest in worldwide mortalities, such as HIV/AIDS, tuberculosis, malaria, measles, and hepatitis.

Oestrogen replacement therapy may improve memory functioning in the absence of APOE epsilon4.

There is currently intense controversy regarding the use of hormone replacement therapy (HRT) in postmenopausal women, in relation to its therapeutic efficacy in Alzheimer's disease (AD). It has been suggested that the benefits of HRT may be modified by apolipoprotein E (APOE) genotype (the major genetic risk factor for AD). Here we report the findings of the first study designed to systematically explore the interaction of (a) oestrogen replacement therapy (ERT) and (b) possession of an epsilon4 allele of APOE on specific elements of episodic learning and memory that are commonly used indices of age-related cognitive decline. This data represents a cross-sectional analysis of the interaction of ERT and APOE genotype on learning and memory in a cohort of 181 healthy postmenopausal women [ERT users (n = 101, mean age 65.40 +/- 6.34); ERT non-users (n = 80, mean age 67.03 +/- 6.80)] residing in Perth, Western Australia. The highest level of learning (trials 2-5; P < 0.05) and memory (e.g. total number of items recalled; P < 0.05) performance was observed in women taking ERT who were not carriers of the APOE epsilon4 allele. APOEepsilon4 carriers receiving ERT performed no better on episodic memory testing than APOE epsilon4 carriers who were not receiving ERT. These cognitive differences related to genetic profile, were noted on both recall and recognition (P = 0.005) tests of memory. The findings have significance for evaluating whether and when ERT may be clinically indicated. Specifically, ERT may benefit the cognitive functioning of women not carrying the APOE epsilon4 allele.

Psychological treatment for recurrent symptoms of colds and flu in children.

The effect of stress management and relaxation with guided imagery on upper respiratory tract infections (URTIs) was investigated in 45 children with a history of 10 or more infections in the past year. To investigate the influence of psychological treatment on mucosal immunity, secretory immunoglobulin A (sIgA) was measured before and during treatment. The number of symptomatic episodes during 13 weeks of monitoring was similar in treatment and waitlist conditions; however, episodes were shorter in stress management and guided imagery conditions than in the waitlist condition. Levels of sIgA increased toward the end of treatment. These findings were confirmed in a replication study. In addition, symptom reduction and improvements in psychological state persisted at 1-year follow-up. The findings suggest that psychological treatment interrupts a chronic illness cycle in children with symptoms of recurrent URTI.

African American female basketball players: an examination of alcohol and drug behaviors.

The use of drugs and alcohol by National Collegiate Athletic Association Division I African American female basketball players and their reasons for using these substances were examined. The investigation is part of a broader study investigating the use of alcohol, weight-loss products, tobacco, amphetamines, and anabolic steroids by female college athletes. Of the 50 athletes in this study, 72% reported having consumed alcoholic beverages, and 46% had engaged in binge drinking. Only 8% reported using either weight-loss or tobacco products, and there were no reports of using amphetamines or anabolic steroids. Usage patterns indicated that the athletes in the study were aware of the short-term negative effects of alcohol and tobacco; those respondents who did use these products greatly reduced their consumption during the competitive season. Factors found to influence use include social and peer influences and coaches' rules.

Potential renal transplant donors: evaluation with gadolinium-enhanced MR angiography and MR urography.

PURPOSE: To determine prospectively the feasibility and accuracy of combined gadolinium-enhanced magnetic resonance (MR) angiography, MR urography, and MR nephrography in the presurgical evaluation of potential renal transplant donors. MATERIALS AND METHODS: Twenty-two potential donors for renal transplantation were evaluated with 1.5-T MR imaging. MR angiograms were evaluated for the number of renal arteries, presence of early arterial branches, and renal artery stenoses. The renal collecting system and ureters were evaluated on the MR urograms. Renal parenchyma was assessed on the MR nephrogram. Prospective interpretation of MR images was compared with that of conventional angiograms and excretory urograms and with surgical findings. RESULTS: Gadolinium-enhanced MR angiography enabled correct identification of the arterial supply to all 44 native kidneys (44 single or dominant renal arteries and nine accessory renal arteries), four of five early arterial branches arising in the proximal 2 cm of the renal artery, a mild truncal stenosis in one renal artery, and two anomalies of the draining renal veins. The MR urogram accurately depicted a duplicated collecting system and mild unilateral pelvicalicectasis. The MR nephrogram showed renal size and a solitary cyst in one kidney, confirmed with sonography. CONCLUSION: Combined gadolinium-enhanced MR angiography, MR urography, and MR nephrography can accurately depict the arterial supply, collecting system, and renal parenchyma of donor kidneys.

Increased psychosocial stress and decreased mucosal immunity in children with recurrent upper respiratory tract infections.

The association between psychosocial stress and susceptibility to upper respiratory tract infection was investigated in 45 children with a history of recurrent colds and flu, and in 45 healthy children of similar age and distribution. In addition, mucosal immune protection against upper respiratory tract infections was assessed by measuring the concentration of secretory immunoglobulin A (sIgA) and its ratio to albumin in saliva. Several dimensions of psychosocial stress, including exposure to stressful experiences, stress-prone personality traits, and signs of emotional disturbance were elevated in children with a history of recurrent colds and flu. Furthermore, lower sIgA/albumin ratios in these children indicated a deficiency in local mucosal immunity. Thus, the findings are consistent with the view that psychosocial stress depletes local immune protection against viral invasion or bacterial colonization of the upper respiratory tract; this depletion may increase susceptibility to colds and flu. Alternatively, psychological disturbances could develop in response to frequent illness.

Secretory immunoglobulin A increases during relaxation in children with and without recurrent upper respiratory tract infections.

A diminished mucosal concentration of secretory immunoglobulin A (sIgA) in the upper respiratory tract may increase susceptibility to colds and flu. The aim of the present study was to determine whether sIgA increases during relaxation in children aged between 8 and 12 years with recurrent upper respiratory tract infections. Forty-five healthy children and 45 children with 10 or more upper respiratory tract infections in the previous year were randomly assigned to one of three experimental conditions: relaxation with suggestions to increase immune system proteins, relaxation alone, or a control condition. Samples of saliva were obtained before and after each condition. The concentration of sIgA in the saliva samples was later determined by measuring the rate of precipitation of antigen-antibody complexes to known concentration of sIgA antigen. The concentration of sIgA increased in the relaxation conditions but not in the control condition. The sIgA/albumin ratio (a more specific measure of local mucosal immunity than concentration) increased during the relaxation-suggestion condition but not during the relaxation or control conditions; however, both the concentration of sIgA and the sIgA/albumin ratio increased in proportion to subjective relaxation ratings. Neither response differed between healthy children and children with recurrent infections. The findings indicate that a disturbance in mucosal immunity in children with recurrent colds and flu does not limit increases in sIgA during relaxation. Higher preinfection levels of sIgA correlate with resistance to upper respiratory tract infection, so enhancing the sIgA concentration with relaxation techniques may help children with recurrent infection problems.

Evaluation of malignant biliary obstruction: efficacy of fast multiplanar spoiled gradient-recalled MR imaging vs spin-echo MR imaging, CT, and cholangiography.

OBJECTIVE: Although CT and cholangiography have proven value in the detection of biliary obstruction, determining the extent of biliary tumors and imaging small pancreatic or ampullar tumors remain problematic. We hypothesized that the superior contrast resolution of MR, coupled with contrast-enhanced breath-hold imaging, might increase the sensitivity for tumor detection and improve the depiction of the point of obstruction in patients with malignant biliary disease. SUBJECTS AND METHODS: Twenty-one MRI studies were performed prospectively in patients with malignant biliary obstruction by obtaining breath-hold contrast-enhanced fast multiplanar spoiled gradient-recalled (FMPSPGR) images at 0 and 10 min, conventional spin-echo T1-weighted images, and fast spin-echo T2-weighted images. Findings on MR images were correlated with findings on CT scans (15 cases) and/or cholangiograms (14 cases) by two observers. All MR images, CT scans, and cholangiograms were reviewed to evaluate tumor detection, visualization of dilated bile ducts, and conspicuity of the obstructing tumor. A four-point scale (1 = excellent tumor depiction and conspicuity, 4 = tumor not detected) was used for evaluation. Contrast-to-noise ratios for tumor and bile were calculated for the three MR pulse sequences. RESULTS: The contrast-enhanced FMPSPGR images and CT scans provided excellent depiction of the dilated biliary tree in 95% and 93% of examinations, respectively, with both techniques superior to fast spin-echo and T1-weighted images (p < .005). Tumor detection was best with the immediate FMPSPGR MR images (20/21), compared with fast spin-echo MR images (16/21) (p = .04), T1-weighted MR images (16/21) (p = .04), CT scans (12/15) (p > .05), and cholangiograms (13/14) (p > .05). Of 13 examinations showing proximal biliary obstruction, the mean score for tumor conspicuity was best with the immediate enhanced FMPSPGR MR images (1.38 +/- .65), compared with T1-weighted MR images (2.38 +/- 1.3) and fast spin-echo MR images (2.08 +/- 1.0) (p < .05), but it was not different from the delayed FMPSPGR MR images (1.75 +/- 1.1) or CT scans (1.9 +/- 0.99) (p > .05). For five of six cholangiocarcinomas, the immediate and delayed enhanced FMPSPGR MR images showed excellent tumor conspicuity owing to their enhancement with gadopentetate dimeglumine. Data for contrast-to-noise ratios of tumor showed that the immediate FMPSPGR MR images (15.8 +/- 10.2) were superior to T1-weighted images (6.3 +/- 3.5, p < .01), but were not different from fast spin-echo images (13.5 +/- 6.7) or delayed FMPSGR images (11.5 +/- 8.9). For eight examinations in patients with distal biliary obstruction, the mean score for tumor conspicuity was greater with the immediate FMPSPGR MR images (1.38 +/- 0.52), compared with fast spin-echo images (3.25 +/- 0.71, p < .005), T1-weighted images (2.63 +/- 1.06, p < .05), and delayed FMPSPGR MR images (2.60 +/- 1.5, p < .05), but was similar to that with CT scans (1.40 +/- 0.89, p > .05). Data for contrast-to-noise ratios of tumor showed an advantage for the immediate FMPSPGR MR images (12.0 +/- 7.7) over T1-weighted images (4.0 +/- 2.6, p < .01) and delayed FMPSPGR images (4.3 +/- 2.6, p < .025), but no difference from fast spin echo images (6.6 +/- 8.8, p = .05). CONCLUSION: Contrast-enhanced FMPSPGR MR imaging is sensitive for the detection of tumors causing biliary obstruction. For proximal obstruction, it may be particularly effective for detecting and defining tumor extent of hilar cholangiocarcinomas because of their enhancement with gadopentetate dimeglumine. For cases of distal obstruction, this technique showed improved tumor detection and conspicuity compared with T1- and fast spin-echo T2-weighted images, but showed no advantage over CT.

Angiography is useful in detecting the source of chronic gastrointestinal bleeding of obscure origin.

The treatment of patients with chronic gastrointestinal bleeding can be a frustrating diagnostic challenge. In the past 10-15 years, a variety of new diagnostic procedures (e.g., fiber-optic endoscopy, scintigraphy, and double-contrast barium studies) have become available to examine these patients. Despite these new procedures, a small number of patients continue to bleed without a defined cause. We sought to evaluate the role of visceral angiography in patients with chronic gastrointestinal bleeding in whom findings on an extensive noninvasive workup have been normal. Between 1983 and 1990, we obtained angiograms on 36 such patients. The cause of bleeding was established by angiography in 16 patients (44%). In 11 of these 16, angiography revealed only a structural abnormality without active bleeding. Twenty patients had normal angiographic findings. No angiograms were false-positive, but three were false-negative (8%). No complication occurred as a result of the angiographic procedures. Our experience shows that visceral angiography can provide a positive diagnosis in a significant number of patients with chronic gastrointestinal bleeding of obscure origin in whom all other diagnostic measures have been unrevealing. Despite improvements in noninvasive diagnostic techniques, angiography still remains an important tool for examining this group of patients.