Interest in genetic testing among first-degree relatives of breast cancer patients

The recent cloning of a breast-ovarian cancer susceptibility gene (BRCA1), and determination of the locus of a related gene (BRCA2), offers potential for clinical genetic testing for breast cancer susceptibility. This study examined interest in and expectations about an impending genetic test among first-degree relatives (FDRs) of breast cancer patients. One hundred five females completed two structured telephone interviews to assess demographics, breast cancer risk factors, psychological factors, and attitudes about genetic testing for breast cancer susceptibility. Overall, 91% of FDRs said that they would want to be tested, 4% said they would not, and 5% were uncertain. The most commonly cited reasons for wanting genetic testing were to learn about one's children's risk, to increase use of cancer screening tests, and to take better care of oneself. Women with less formal education were motivated by childbearing decisions and future planning to a greater degree than were women with education beyond high school. Most women anticipated a negative psychological impact of positive test results, involving increased anxiety (83%), depression (80%), and impaired quality of life (46%). In addition, 72% of women indicated that they would still worry if they tested negative. In multivariate regression analysis, level of baseline depression was the strongest predictor of an anticipated negative impact of genetic testing (Beta =.15; P,.0001). These results suggest that the demand for genetic testing for breast cancer susceptibility may be great, even among women who are not likely to have predisposing mutations. Prior to widespread availability of such testing, it will be critical to develop informed consent protocols to educate individuals about the benefits and limitations of predictive testing for this multifactorial disease. © 1995 Wiley-Liss, Inc.     

Antimicrobial resistance of Shiga toxin (verotoxin)-producing Escherichia coli O157:H7 and non-O157 strains isolated from humans, cattle, sheep and food in Spain

A total of 722 Shiga toxin-producing Escherichia coli (STEC) isolates recovered from humans, cattle, ovines and food during the period from 1992 to 1999 in Spain were examined to determine antimicrobial resistance profiles and their association with serotypes, phage types and virulence genes. Fifty-eight (41%) out of 141 STEC O157:H7 strains and 240 (41%) out of 581 non-O157 STEC strains showed resistance to at least one of the 26 antimicrobial agents tested. STEC O157:H7 showed a higher percentage of resistant strains recovered from bovine (53%) and beef meat (57%) than from human (23%) and ovine (20%) sources, whereas the highest prevalence of antimicrobial resistance in non-O157 STEC was found among isolates recovered from beef meat (55%) and human patients (47%). Sulfisoxazole (36%) had the most common antimicrobial resistance, followed by tetracycline (32%), streptomycin (29%), ampicillin (10%), trimethoprim (8%), cotrimoxazole (8%), chloramphenicol (7%), kanamycin (7%), piperacillin (6%), and neomycin (5%). The multiple resistance pattern most often observed was that of streptomycin, sulfisoxazole, and tetracycline. Ten (7%) STEC O157:H7 and 71 (12%) non-O157 strains were resistant to five or more antimicrobial agents. Most strains showing resistance to five or more antimicrobial agents belonged to serotypes O4:H4 (4 strains), O8:H21 (3 strains), O20:H19 (6 strains), O26:H11 (8 strains eae-beta1), O111:H- (3 strains eae-gamma2), O118:H- (2 strains eae-beta1), O118:H16 (5 strains eae-beta1), O128:H- (2 strains), O145:H8 or O145:H- (2 strains eae-gamma1), O157:H7 (10 strains eae-gamma1), O171:H25 (3 strains), O177:H11 (5 strains eae-beta1), ONT:H- (3 strains/1 eae-beta1) and ONT:H21 (2 strains). Interestingly, most of these serotypes, i.e., those indicated in bold) were found among human STEC strains isolated from patients with hemolytic uremic-syndrome (HUS) reported in previous studies. We also detected, among non-O157 strains, an association between a higher level of multiple resistance to antibiotics and the presence of the virulence genes eae and stx(1). Moreover, STEC O157:H7, showed an association between certain phage types, PT21/28 (90%), PT23 (75%), PT34 (75%), and PT2 (54%), with a higher number of resistant strains. We conclude that the high prevalence of antimicrobial resistance detected in our study is a source of concern, and cautious use of antibiotics in animals is highly recommended.     

The Role of Trait Anxiety in Nicotine Dependence1

Studies point to an association between anxiety and smoking. However, the mechanisms linking trait anxiety and nicotine dependence have not been evaluated fully. Potential mediators include self-medication variables (e.g., use of nicotine to manage anxiety) and cognitive variables (e.g., lower levels of self-efficacy). The present study explored these mechanisms in a sample of 352 male and female smokers. The results showed that trait anxiety correlated significantly with negative affect smoking (r= .29, p= .0001), stimulation smoking (r=.15, p = .007), and nicotine dependence (r= .20, p= .0003). Trait anxiety also correlated significantly with self-efficacy (r =-.22, p = .0003). Regression analyses revealed that trait anxiety predicted nicotine dependence after controlling for depression, education, race, age, and marital status (R²= .09, p = .0001). Path modeling indicated that both negative affect smoking and quitting self-efficacy mediated the relationship between trait anxiety and nicotine dependence. Interventions that emphasize the management of anxious mood and quitting confidence may benefit anxious smokers.     

Monozygotic twinning after assisted reproductive techniques: a phenomenon independent of micromanipulation

A 3 year retrospective analysis was conducted of pregnancies achieved after various assisted reproductive treatment modalities in our infertility practice, to calculate and compare the rates of monozygotic twinning (MZT). A total of 731 pregnancies achieved after various assisted reproduction treatments were reviewed. Gonadotrophin therapy for induction of ovulation and controlled ovarian hyperstimulation (COH) yielded 129 clinical pregnancies. Conventional IVF yielded 139 pregnancies. IVF and intracytoplasmic sperm injection (ICSI) with or without assisted hatching (AH) yielded 463 pregnancies, all during the same time period. The rates of multiple pregnancy (monozygotic and dizygotic) twins and triplets were recorded. MZT was found in 1.5% of ovulation induction or COH pregnancies (2/129). The incidence of MZT after conventional IVF was 0.72% (1/139). After IVF-ICSI/AH, MZT was found in 0.86% (4/463). The overall rate of MZT was 0.95% (7/731). Five cases were dizygotic triplets and two cases were monozygotic twins. We found the rate of MZT after assisted reproduction treatment increased more than two-fold over the background rate in the general population. Dizygotic triplets were found more often than monozygotic twins. The rate of MZT was consistently increased, irrespective of treatment modality or micromanipulation. This may signify that the aetiology of increased MZT after assisted reproduction is the gonadotrophin treatment rather than in-vitro conditions, micromanipulation, or multiple embryo transfer.     

Polyclonal 111In-IgG, 125I-LDL and 125I-endothelin-1 accumulation in experimental arterial wall injury

To test iodine-125 labelled low-density lipoprotein (¹²⁵I-LDL), polyclonal indium-111 labelled immunoglobulin G (¹¹¹In-IgG) and iodine-125 labelled endothelin-1 uptake in metabolically active atheromatous plaques after arterial wall injury, we performed balloon de-endothelialization of carotid arteries or abdominal aortas in 24 New Zealand male rabbits which were fed with a normal diet (n=14) or a hypercholesterolaemic diet (n=10) after surgery. Six weeks later the animals were injected with 200 Ci of (¹²⁵I-LDL), and/or with 100 Ci of ¹¹¹In-IgG or with 9 Ci of ¹²⁵I-endothelin-1. Forty-eight hours later the animals were sacrificed. Carotid arteries and aortas were removed, counted and fixed for autoradiography and light microscopy examination. Contralateral carotid arteries and thoracic aortas served as controls.Significant ¹¹¹In-IgG uptake was observed in the injured arteries at autoradiography, with localization mainly in the healing edges, and at well counting. The percentage of the injected dose per gram (%D.inj/g) was 0.0188±0.06 versus 0.0059±0.003 in controls (P< 0.05). There was no difference in ¹¹¹In-IgG uptake between arteries with injury alone and those with active atheroma formation at the site of the injury. Significant (¹²⁵I-LDL), uptake was observed only when lipid deposition was present at light microscopy (%D.inj/g of 0.0024±0.0005 vs 0.0010±0.0003 in controls, P < 0.05). ¹²⁵I-endothelin-1 accumulation was observed in four of five injured aortas both at autoradiography, with diffuse localization, and at well counting (%D.inj/g of 0.0012±0.0004 in the abdominal aortas vs 0.0008±0.0003 in the thoracic aortas).Polyclonal IgG may accumulate in injured arteries without active atheroma formation. Inflammatory reaction at the site of the injury may cause ¹¹¹In-IgG uptake independently of atheromatous plaque formation. LDL accumulation takes place only with active atheroma formation at the site of the injury. Use of labelled peptides such as endothelin-1 may provide further insight into the mechanisms of atheromatous plaque formation.     

Diarrheal deaths in the United States, 1979 through 1987. A special problem for the elderly

OBJECTIVE.--Diarrhea is an important cause of death among young children in both developing and developed countries, but little is known about diarrheal death among adults. In this study, we examined trends in diarrheal deaths among all age groups in the United States. DESIGN/SETTING/PARTICIPANTS.--We reviewed national mortality data complied by the National Center for Health Statistics, Hyattsville, Md, which consists of information from all death certificates filed in the United States for the period 1979 through 1987. A death for which diarrhea was listed as an immediate or underlying cause was considered a "diarrheal death" and included in the analysis. RESULTS.--We found that 28,538 persons died of diarrhea cited as either an immediate or the underlying cause of death during the 9-year period. A majority of diarrheal deaths occurred among the elderly (older than 74 years of age, 51%), followed by adults 55 to 74 years of age (27%), and young children (younger than 5 years of age, 11%). For the elderly, adjusted risk factors for dying of diarrhea included being white, female, and residing in a long-term care facility. Only the elderly and young children had clear, distinct winter peaks of diarrheal deaths, suggesting that the diarrhea may, in part, be infectious in origin. CONCLUSION.--For the elderly, more directed studies of those at risk, such as nursing home residents, are needed to determine if oral rehydration therapy, vaccines, or other preventive measures might benefit this population.     

Target RNA capture and cleavage by the Cmr type III-B CRISPR–Cas effector complex

The effector complex of the Cmr/type III-B CRISPR (clustered regularly interspaced short palindromic repeat)–Cas (CRISPR-associated) system cleaves RNAs recognized by the CRISPR RNA (crRNA) of the complex and includes six protein subunits of unknown functions. Using reconstituted Pyrococcus furiosus Cmr complexes, we found that each of the six Cmr proteins plays a critical role in either crRNA interaction or target RNA capture. Cmr2, Cmr3, Cmr4, and Cmr5 are all required for formation of a crRNA-containing complex detected by native gel electrophoresis, and the conserved 5′ repeat sequence tag and 5′-OH group of the crRNA are essential for the interaction. Interestingly, capture of the complementary target RNA additionally requires both Cmr1 and Cmr6. In detailed functional studies, we determined that P. furiosus Cmr complexes cleave target RNAs at 6-nucleotide (nt) intervals in the region of complementarity, beginning 5 nt downstream from the crRNA tag and continuing to within ∼14 nt of the 3′ end of the crRNA. Our findings indicate that Cmr3 recognizes the signature crRNA tag sequence (and depends on protein–protein interactions with Cmr2, Cmr4, and Cmr5), each Cmr4 subunit mediates a target RNA cleavage, and Cmr1 and Cmr6 mediate an essential interaction between the 3′ region of the crRNA and the target RNA.