Evidence for linkage of nonsyndromic cleft lip with or without cleft palate to a region on chromosome 2

Results from a genome-wide screen of 10 multiplex families ascertained through probands with nonsyndromic cleft lip with or without cleft palate (CL/P) in Mexico, Argentina, and the United States yielded suggestive evidence of linkage to chromosomes 2, 6, 17 and 18. Fine mapping excluded all regions except chromosome 2. Subsequent analysis was performed on the original 10 families plus an additional 16 families using 31 markers on chromosome 2. This analysis showed intriguing evidence of linkage to 2q (Zlr=2.26, empirical P-value=0.028 in a chromosome-wide analysis). Transmission disequilibrium tests also revealed evidence of linkage and disequilibrium for two markers in this region (D2S168 and D2S1400 with P-values=0.022 and 0.006, respectively). A subset of these 26 families provided additional evidence for a susceptibility gene for CL/P on 2q, suggesting that further studies of genes in this region are warranted.     

The effect of RANTES chemokine genetic variants on early HIV-1 plasma RNA among African American injection drug users

HIV-1 plasma RNA is a prognostic indicator of HIV-1, and increased levels of HIV-1 plasma RNA are associated with rapid progression to AIDS. Because chemokines and chemokine receptors are involved in the binding and entry of HIV-1, possible effects of host genetics on viral RNA levels should be visible in early infection. HIV-1 plasma RNA was measured within 2 years of seroconversion in 198 seroincident injection drug users followed in the AIDS Link to Intravenous Experience cohort. Genetic variants were identified in the chemokine receptors (CCR2, CCR5, and CCR5 promoter) and the chemokine RANTES using TaqMan and restriction fragment length polymorphism assays. Linear regression of RANTES haplotypes on early HIV-1 plasma RNA identified individuals homozygous for the RANTES R1 haplotype as having a lower viral load by almost one-half log10 unit compared with those bearing non-RANTES R1 haplotypes (-0.43, 95% confidence interval: -0.74, -0.12). Genetic variants in RANTES may downregulate RANTES gene expression and increase early HIV-1 plasma RNA. Because RANTES is a critical chemokine and competitively inhibits HIV-1 by binding to its receptor CCR5, treatment to enhance RANTES expression may assist in delaying the progression of AIDS by decreasing the initial viral load.     

Effect of Condoms on Reducing the Transmission of Herpes Simplex Virus Type 2 From Men to Women

Context  Herpes simplex virus type 2 (HSV-2) is one of the most common sexually transmitted infections in the United States. No prospective study has shown the ability of condoms to reduce transmission of HSV-2. Objective  To evaluate risk factors for HSV-2 acquisition and efficacy of condoms in prevention of HSV-2 transmission. Design  Analysis of data from a randomized, double-blind, placebo-controlled trial conducted December 13, 1993, to June 28, 1996, of an ineffective candidate HSV-2 vaccine with 18 months of follow-up. Setting  Eighteen clinical trial centers in the United States. Participants  A total of 528 monogamous couples discordant for HSV-2 infection, including an HSV-2–susceptible population of 261 men and 267 women. Main Outcome Measure  Acquisition of HSV-2 infection by susceptible partners, compared with those remaining free of HSV-2 with regard to demographic characteristics, sexual activity, and condom use. Results  Twenty-six women (9.7%) vs 5 men (1.9%) acquired HSV-2, for a rate per 10 000 sex acts (episodes of sexual intercourse) of 8.9 vs 1.5, respectively (P<.001). In multivariable analysis, younger age (adjusted hazard ratio [HR] per 5 years, 1.57; 95% confidence interval [CI], 1.22-2.04), seropositivity for HSV-1 and HSV-2 vs HSV-2 alone in the source partner (adjusted HR, 2.34; 95% CI, 1.14-4.82), and more frequent sexual activity (adjusted HR per additional sex act per week, 1.10; 95% CI, 1.01-1.19) were associated with higher risk of HSV-2 acquisition. Condom use during more than 25% of sex acts was associated with protection against HSV-2 acquisition for women (adjusted HR, 0.085; 95% CI, 0.01-0.67) but not for men (adjusted HR, 2.02; 95% CI, 0.32-12.50). Risk of HSV-2 transmission declined from 8.5 per 100 person-years in the initial 150-day interval to 0.9 per 100 person-years in the final 150-day interval (P = .002 for trend), concurrent with a decrease in sexual activity and proportion of sex acts occurring when the source partner had genital lesions. Conclusions  Condom use offers significant protection against HSV-2 infection in susceptible women. Changes in sexual behavior, correlated with counseling about avoiding sex when a partner has lesions, were associated with reduction in HSV-2 acquisition over time. These data suggest that identification of discordant couples can reduce transmission of HSV-2, especially for heterosexual couples in which the male partner has HSV-2 infection.      

Are there “Better” and “Worse” Ways to be Consensually Non-Monogamous (CNM)?: CNM Types and CNM-Specific Predictors of Dyadic Adjustment

Research on consensual non-monogamy (CNM) has largely been restricted to comparisons between monogamous and CNM people, with researchers paying little attention to various CNM styles. The current research elucidated differences among three styles of CNM: open relationships, polyamory, and swinging. Across three studies, we demonstrated that people in polyamorous or swinger-style relationships have higher levels of relationship satisfaction and other relational outcomes (e.g., passionate love, trust) than those in open relationships. That is, people in open relationships consistently fared more poorly in their relational outcomes than those in other types of CNM relationships. In Studies 4 and 5, we isolated some of the reasons for these differences. We found that differences in relational outcomes between open-style and other styles of CNM dissipated when controlling for (a) couples’ approach to communication, (b) extrinsic versus intrinsic motivations for participating in CNM, (c) adherence to pro-monogamy beliefs and (d) degree of contact with one’s partner’s partners (“metamours”). Thus, CNM-specific relational dynamics are associated with dyadic adjustment in these relationships.

     

Communication Patterns Among Male Couples with Open and Monogamous Agreements

Archives of Sexual Behavior - Male couples in open relationships tend to have as equally fulfilling relationships as monogamous male couples; however, less is known about communication differences...     

Laser Doppler velocimetry in retinal arteries of infants

The present study was conducted to assess the feasibility of laser Doppler velocimetry in young infants, as a prelude to ultimately undertaking such measurements in premature infants. A portable, unidirectional laser Doppler velocimeter was developed based on a Kowa RC-2 hand-held fundus camera. Six infants between 1 and 21 weeks of age were studied. Relative red blood cell velocity (f_max) at the centre of retinal arteries was measured over approximately 10 heart cycles. A pulsatility parameter (P=1–f_max.dia/f_max.sys), a summary index of vascular status, was determined from the average diastolic and systolic values of f_max. Velocity waveforms were obtained in four of the six infants. Arterial pulsatility for the group was 0.63±0.13. Precise non-invasive measurement of arterial red blood cell velocity waveforms in young infants was achieved. The high signal-to-noise ratio and temporal resolution of this data suggest that relative measurements of retinal blood flow may permit assessment of haemodynamic changes in premature infants.     

Chemotherapy for desmoid tumours in association with familial adenomatous polyposis: a report of three cases

Objective

To determine the efficacy of chemotherapy for inoperable desmoid tumours associated with familial adenomatous polyposis.

Design

A review of three cases of unresectable desmoid tumours and of the literature on the subject.

Setting

The Steven Atanas Stavro Polyposis Registry at Mount Sinai Hospital in Toronto.

Patients

Three patients with symptomatic, unresectable desmoid tumours associated with familial adenomatous polyposis and unresponsive to conventional hormone therapy.

Intervention

A chemotherapy regimen of seven cycles of doxorubicin (dose ranging from 60 to 90 mg/m²) and dacarbazine (1000 mg/m²), followed by carboplatin (400 mg/m²) and dacarbazine.

Outcome Measures

Clinical improvement and tumour regression demonstrated by computed tomography.

Results

In each of the three cases significant tumour regression was seen clinically and radiologically.

Conclusions

Cytotoxic chemotherapy is an effective treatment for desmoid tumours associated with familial adenomatous polyposis. The chemotherapy should be started early in cases of symptomatic desmoid tumour unresponsive to conventional medical therapy.     

Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians.

Exposure to heterocyclic amines may increase prostate cancer risk. Human sulfotransferase 1A1 (SULT1A1) is involved in the bioactivation of some dietary procarcinogens, including the N-hydroxy metabolite of the food-borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo(4,5-b) pyridine. This study compares a polymorphism in the SULT1A1 gene, SULT1A1 enzyme activity, meat consumption, and the risk of prostate cancer in a population based case-control study. Prostate cancer patients (n = 464) and control individuals (n = 459), frequency matched on age and ethnicity, provided informed consent, answered a survey, and provided a blood sample. Platelets were isolated for phenotype analysis, and DNA was isolated from lymphocytes for genotype determination. Meat consumption was assessed using a dietary questionnaire. Caucasians homozygous for the SULT1A1*1 high activity allele were at increased risk for prostate cancer [odds ratio (OR), 1.68; 95% confidence interval (CI), 1.05-2.68] compared with individuals homozygous for the low-activity allele. The association between SULT1A1 genotype and prostate cancer risk in African-Americans did not reach significance (OR, 1.60; 95% CI, 0.46-5.62). When SULT1A1 activity was considered, there was a strong association between increased SULT1A1 activity and prostate cancer risk in Caucasians (OR, 3.04; 95% CI, 1.8-5.1 and OR, 4.96; 95% CI, 3.0-8.3, for the second and third tertiles of SULT1A1 activity, respectively) compared with individuals in the low enzyme activity tertile. A similar association was also found in African-American patients, with ORs of 6.7 and 9.6 for the second and third tertiles of SULT1A1 activity (95% CI, 2.1-21.3 and 2.9-31.3, respectively). When consumption of well-done meat was considered, there was increased risk of prostate cancer (OR, 1.42; 95% CI, 1.01-1.99 and OR, 1.68; 95% CI, 1.20-2.36 for the second and third tertiles, respectively). When SULT1A1 activity was stratified by tertiles of meat consumption, there was greater risk of prostate cancer in the highest tertile of meat consumption. These results indicate that variations in SULT1A1 activity contributes to prostate cancer risk and the magnitude of the association may differ by ethnicity and be modified by meat consumption.     

Segregation analysis of 231 Ashkenazi Jewish families for evidence of additional breast cancer susceptibility genes.

Between 5 and 10% of breast cancer is attributable to inherited cancer susceptibility genes. Mutations in the genes BRCA1 and BRCA2 account for two-thirds of hereditary breast cancer cases. Using segregation analysis, families of cases without BRCA1/2 mutations were studied for statistical evidence of another major breast cancer gene in a community-based sample of Jewish probands tested previously for the presence of three BRCA founder mutations. A total of 231 probands with breast cancer, who do not carry a founder mutation, reported complete data on 602 female first-degree relatives of probands over age 20; 78 of these relatives had breast cancer. Segregation analysis was used to evaluate the likelihood of various genetic and nongenetic models. Sporadic, environmental, and general Mendelian genetic models fit the family data poorly and were rejected. A Mendelian recessive model fit better than dominant and codominant models, although none of these could be rejected. Cumulative incidence curves predicted by the recessive and codominant models fit observed incidence among first-degree relatives well. The assumption of Mendelian transmission of a major recessive gene(s) is compatible with the data. The recessive model predicts that 4% of women would carry the high-risk genotype, with 85% of them developing breast cancer by age 70. There was significant heterogeneity between these families and the 114 BRCA1/2 mutation-positive families from the same study population, implying that this apparent recessive effect is not because of undetected BRCA1/2 mutations. The study adds support for a major autosomal recessive component to breast cancer susceptibility.     

Patient Satisfaction, Treatment Experience, and Disability Outcomes in a Population-Based Cohort of Injured Workers in Washington State: Implications for Quality Improvement

Objective. To determine what aspects of patient satisfaction are most important in explaining the variance in patients' overall treatment experience and to evaluate the relationship between treatment experience and subsequent outcomes.
Data Sources and Setting. Data from a population-based survey of 804 randomly selected injured workers in Washington State filing a workers' compensation claim between November 1999 and February 2000 were combined with insurance claims data indicating whether survey respondents were receiving disability compensation payments for being out of work at 6 or 12 months after claim filing.
Study Design. We conducted a two-step analysis. In the first step, we tested a multiple linear regression model to assess the relationship of satisfaction measures to patients' overall treatment experience. In the second step, we used logistic regression to assess the relationship of treatment experience to subsequent outcomes.
Principal Findings. Among injured workers who had ongoing follow-up care after their initial treatment ( n =681), satisfaction with interpersonal and technical aspects of care and with care coordination was strongly and positively associated with overall treatment experience ( p <0.001). As a group, the satisfaction measures explained 38 percent of the variance in treatment experience after controlling for demographics, satisfaction with medical care prior to injury, job satisfaction, type of injury, and provider type. Injured workers who reported less-favorable treatment experience were 3.54 times as likely (95 percent confidence interval, 1.20–10.95, p= .021) to be receiving time-loss compensation for inability to work due to injury 6 or 12 months after filing a claim, compared to patients whose treatment experience was more positive.