Association of HPC2/ELAC2 polymorphisms with risk of prostate cancer in a population-based study.

Genetic polymorphism in HPC2/ELAC2 was recently associated with risk of sporadic prostate cancer. To determine the contribution of two HPC2/ELAC2 missense variants (Ser217Leu and Ala541Thr) to the risk of developing prostate cancer, we conducted a population-based case-control study of middle-aged men (40-64 years). Cases (n=591) were ascertained from the Seattle-Puget Sound Surveillance, Epidemiology, and End Results Cancer Registry and Controls (n=538) from the same general population were identified through random-digit dialing. Subjects were residents of King County, Washington, and were frequency matched on age. Cases (32%) had a slightly higher frequency of the Leu217 variant compared with controls (29%), but there were no differences in the frequency of the Thr541 allele (4%). When considering joint genotypes, white men homozygous for the Leu217 variant on an Ala541/Ala541 background had an increased risk of prostate cancer [odds ratio (OR)=1.84; 95% confidence interval (CI), 1.11-3.06]. Different risk profiles were also observed when cases were stratified by disease aggressiveness. Men with at least one Leu217 allele had an elevated risk (OR=1.34; 95% CI, 1.02-1.76) of less aggressive prostate cancer (localized stage and Gleason score < or = 7), with a stronger association among men with two Leu217 alleles (OR=1.73; 95% CI, 1.08-2.77). The Ala541Thr polymorphism was not associated with risk, and neither variant was associated with more aggressive prostate cancer phenotypes. We estimate that the Ser217Leu genotype may account for approximately 14% of less aggressive prostate cancer cases and 9% of all sporadic cases in the general United States population of white men 相似文献   

Urogenital ageing and its effect on sexual health in older British women

Objective To provide information on the extent of problems of urogenital ageing in older British women.
Design A MORI survey of a representative population sample of older British women.
Setting Home interviews.
Participants Two thousand and forty-five women aged 55–85+.
Results Urogenital symptoms had affected 48.8% of the women at some time, but no more than 11% were currently affected by individual symptoms; however, these were often of long duration. The majority (73%) were not sexually active, with lack of a partner being a factor for many. There was also a decreasing prevalence of sexual activity with increasing age. Those sexually active in the 65–74 year old age group (   n = 148  ) tended to have a similar sexual frequency (at least once per month) compared with the younger women studied. Approximately 12% of those who reported dyspareunia and/or vaginal dryness claimed a severe problem; 33% did not seek professional advice and 36% resorted to an over the counter remedy. Use of hormone replacement therapy was generally of relatively short duration. There was a declining gradient of ever-use with age.
Conclusions The extent of significant urogenital symptoms is relatively low, but some women are seriously affected and use self-help as well as professional assistance. The extent of sexual activity in older women and factors affecting this have been defined, and the effect of urogenital symptoms on sexual activity demonstrated.     

Cancer Patterns in the Middle East Special Report from the Middle East Cancer Society

To update its cancer statistics, the newly established Middle East Cancer Society examined the cancer frequency patterns in Egypt and the Gaza Strip. The results revealed differing overall patterns. For men the highest frequencies were found for lymphoma, bladder cancer and cancers of the oral cavity and pharynx in Egypt, and for lung cancer, leukaemia and lymphoma in Gaza. For women, breast cancer had the highest frequency in both areas, followed by cancers of the oral cavity and pharynx in Egypt, and leukaemia and lymphoma in Gaza. The distribution of cancer occurrence by organ system also varied. In the light of the different ethnicities, lifestyles, socioeconomic levels and carcinogenic exposure among the countries of the Middle East, this kind of comparison can provide the background for more sophisticated approaches for discerning risk factors in cancer. We believe that further cooperation among participating countries will overcome the present limitations in data collection, registration and access.     

Behavioral tolerance to lysergic acid diethylamide is associated with reduced serotonin-2A receptor signaling in rat cortex.

Tolerance is defined as a decrease in responsiveness to a drug after repeated administration. Tolerance to the behavioral effects of hallucinogens occurs in humans and animals. In this study, we used drug discrimination to establish a behavioral model of lysergic acid diethylamide (LSD) tolerance and examined whether tolerance to the stimulus properties of LSD is related to altered serotonin receptor signaling. Rats were trained to discriminate 60 microg/kg LSD from saline in a two-lever drug discrimination paradigm. Two groups of animals were assigned to either chronic saline treatment or chronic LSD treatment. For chronic treatment, rats from each group were injected once per day with either 130 microg/kg LSD or saline for 5 days. Rats were tested for their ability to discriminate either saline or 60 microg/kg LSD, 24 h after the last chronic injection. Rats receiving chronic LSD showed a 44% reduction in LSD lever selection, while rats receiving chronic vehicle showed no change in percent choice on the LSD lever. In another group of rats receiving the identical chronic LSD treatment, LSD-stimulated [35S]GTPgammaS binding, an index of G-protein coupling, was measured in the rat brain by autoradiography. After chronic LSD, a significant reduction in LSD-stimulated [35S]GTPgammaS binding was observed in the medial prefrontal cortex and anterior cingulate cortex. Furthermore, chronic LSD produced a significant reduction in 2,5-dimethoxy-4-iodoamphetamine-stimulated [35S]GTPgammaS binding in medial prefrontal cortex and anterior cingulate cortex, which was blocked by MDL 100907, a selective 5-HT2A receptor antagonist, but not SB206553, a 5-HT2C receptor antagonist, indicating a reduction in 5-HT2A receptor signaling. 125I-LSD binding to 5-HT2A receptors was reduced in cortical regions, demonstrating a reduction in 5-HT2A receptor density. Taken together, these results indicate that adaptive changes in LSD-stimulated serotonin receptor signaling may mediate tolerance to the discriminative stimulus effects of LSD.     

Tobacco and Alcohol Use as an Explanation for the Association Between Externalizing Behavior and Illicit Drug Use Among Delinquent Adolescents

The prevalence and persistence of adolescent substance use and abuse is a national health issue, and substance use among adolescents is frequently comorbid with other psychiatric disorders. Most studies in this area utilize samples of middle or high school students or from inpatient settings. Less is known about substance use and psychiatric comorbidity among delinquent adolescents. The present study examined data from two cohorts of juvenile offenders collected over a 2-year period (n = 245, n = 299). Participants reported frequency of cigarette, alcohol, marijuana, and other substance use. Participants' parents completed a measure of behavior problems. Path analyses suggested that parental reports of externalizing problems were significantly related to self-reported substance use while parental reports of internalizing problems were not. Results also suggested that smoking and alcohol use act as mediators between externalizing problems and marijuana and other drug use. Although there were some mean differences by gender, the pattern of relationships amongst the variables did not differ by gender. Implications of the findings and future directions are discussed.     

Using an immunization registry: effect on practice costs and time.

INTRODUCTION: Immunization registries can consolidate immunization records scattered among different providers, allowing immunization documentation for legal purposes, generation of needed-immunization lists, inventory management, and outreach for underimmunized children. They have been endorsed by the Centers for Disease Control and Prevention and health professionals as a means of sustaining high immunization rates. However, some providers perceive the cost of registry use as a barrier to participation. We sought to determine the effects of registry use on cost and time. METHODS: We used a pre-post design and a cost-accounting approach to measure labor costs and time for immunization-related activities possibly affected by registry use before development of a regional registry in Colorado and after the registry was being fully used. Two rural family practices, 2 rural community health centers (CHCs), 3 urban pediatric practices, and 2 rural public health agencies participated in both periods. RESULTS: Cost per shot increased slightly in the postregistry period for private practices and CHCs ($0.56 per shot in 2001 dollars) and public health agencies ($0.38). Since costs can increase for several reasons, including salary increases above inflation, we analyzed time spent per shot and found that staff time decreased for private practices and CHCs but increased substantially for public health agencies. CONCLUSIONS: The study findings suggest to private practices that registry participation can provide a net benefit by making the vaccination process more efficient and, absent above-average salary increases, less costly. Public health agencies, however, would have to rely exclusively on the registry and eschew the use of paper vaccination records to realize efficiencies seen by other practice types.     

Quality improvement in immunization delivery following an unsuccessful immunization recall.

OBJECTIVES: Within a clinic serving disadvantaged children, 1) to evaluate a multifaceted quality improvement (QI) project to improve immunization (IZ) up-to-date (UTD) rates and 2) to assess the efficacy of IZ reminder/recall performed following QI. METHODS: A year-long QI project followed by a trial of reminder/recall. QI interventions were targeted at previously identified barriers to IZ and were designed specifically to improve the efficacy of reminder/recall. QI interventions were designed to 1) increase the use of medical record releases to document IZs received elsewhere; 2) improve the accuracy of parental contact information; and 3) reduce missed opportunities by utilizing chart prompts, provider education, and provider reminders. Following QI, we conducted a randomized trial of reminder/recall. RESULTS: UTD rates for 7-11 month olds increased from 21% before the QI project to 52% after (P <.0001); rates for 12-18 month olds increased from 16% before QI to 44% after (P <.0001); 19-25 month olds 18% before to 33% after (P <.001). After QI, an average of 61 records per month were updated with IZs received elsewhere. However, the accuracy of parental contact information worsened (29% unreachable before QI vs 44% after, P <.001) and missed opportunities did not improve (8% before vs 6% after, P = not significant [NS]). A subsequent trial of reminder/recall did not increase UTD rates, with 17% of recalled children brought UTD vs 16% of controls (P = NS). CONCLUSIONS: Clinic-based QI increased documented UTD rates in a disadvantaged patient population. However, IZ reminder/recall did not further increase UTD rates above the rates achieved by the QI process.     

Complement, fetal antigen, and shaking rigors in parturients.

OBJECTIVES: To assess the relationship, if any, between complement, fetal antigen, and shaking rigors during labor and delivery. METHODS: We recruited 13 volunteers for serial blood sampling during labor and childbirth. RESULTS: Complement levels had a small but significant drop (11-15%) immediately following childbirth but had no association with fetal antigen levels or shaking rigors. Fetal antigen levels failed to show any consistent relationship with shaking rigors or the labor and delivery process. CONCLUSION: Shaking rigors do not appear to be associated with changes in either complement or fetal antigen levels. Complement levels remain stable during labor but drop immediately following birth.     

PBPK model for radioactive iodide and perchlorate kinetics and perchlorate-induced inhibition of iodide uptake in humans.

Detection of perchlorate (ClO4-) in several drinking water sources across the U.S. has lead to public concern over health effects from chronic low-level exposures. Perchlorate inhibits thyroid iodide (I-) uptake at the sodium (Na+)-iodide (I-) symporter (NIS), thereby disrupting the initial stage of thyroid hormone synthesis. A physiologically based pharmacokinetic (PBPK) model was developed to describe the kinetics and distribution of both radioactive I- and cold ClO4- in healthy adult humans and simulates the subsequent inhibition of thyroid uptake of radioactive I- by ClO4-. The model successfully predicts the measured levels of serum and urinary ClO4- from drinking water exposures, ranging from 0.007 to 12 mg ClO4-/kg/day, as well as the subsequent inhibition of thyroid 131I- uptake. Thyroid iodine, as well as total, free, and protein-bound radioactive I- in serum from various tracer studies, are also successfully simulated. This model's parameters, in conjunction with corresponding model parameters established for the male, gestational, and lactating rat, can be used to estimate parameters in a pregnant or lactating human, that have not been or cannot be easily measured to extrapolate dose metrics and correlate observed effects in perchlorate toxicity studies to other human life stages. For example, by applying the adult male rat:adult human ratios of model parameters to those parameters established for the gestational and lactating rat, we can derive a reasonable estimate of corresponding parameters for a gestating or lactating human female. Although thyroid hormones and their regulatory feedback are not incorporated in the model structure, the model's successful prediction of free and bound radioactive I- and perchlorate's interaction with free radioactive I- provide a basis for extending the structure to address the complex hypothalamic-pituitary-thyroid feedback system. In this paper, bound radioactive I- refers to I- incorporated into thyroid hormones or iodinated proteins, which may or may not be bound to plasma proteins.