Determination of capillary leakage due to recombinant interleukin-2 by means of noninvasive conductivity measurements

Summary One of the most common side effects of treatment with recombinant interleukin-2 (IL-2) is capillary leakage. Its genesis is not completely understood. The aim of the study was to determine whether capillary leakage can be monitored by means of a non-invasive conductivity technique and to study its starting point. Eight patients with advanced renal cell cancer were studied in a medium care section of the Department of Medical Oncology, University Hospital over 4 days during treatment sessions of continuous, intravenously administered IL-2 (mean dose of 15.6 × 10⁶ IU · m^–2 · day ^–1). The fluid shift from the intravascular to the extra- and intracellular compartments was monitored by means of noninvasive conductivity measurements. Changes in blood volume were calculated from serial erythrocyte counts. The clinical parameters of capillary leakage (oliguria, positive fluid balance, and gain in mass) were recorded. The mean gain in mass was 9% after 4 days of IL-2 treatment. The extracellular fluid volume increased significantly [46 (SD 23.2)%; P < 0.01], whereas the intracellular fluid volume did not change. The increase in blood volume (BV) amounted to 7% (P < 0.05). The decline in albumin concentration was significantly more than the increase in BV [38 (SD 4.3) %; P < 0.01], indicating capillary albumin leakage. The main changes were observed after the 2nd day of treatment. From this study, it is suggested that conductivity measurements are a suitable method to monitor capillary leakage induced by IL-2, and could be used to detect the exact onset and severity of this leakage. The leakage started within the first 24 h of treatment and was detected as a fluid shift from the intravascular to the extracellular space, while the intracellular compartment remained stable. These measurements could be useful during intervention studies with the aim of preventing this adverse effect of IL-2.     

Soy isoflavones, body composition, and physical performance

OBJECTIVES: Physiologic changes, occurring during the process of aging, can have serious health consequences, such as increased risk of chronic disease and disability. Decline in estradiol levels after menopause is hypothesized to contribute to this risk. Thus, hormone therapy (HT) might prevent or delay those changes. However, HT has serious side effects and alternative approaches are needed. METHODS: We performed a 12-month double-blind randomized trial comparing soy protein containing 99mg isoflavones (aglycone weights) with milk protein (placebo) daily in 202 postmenopausal women aged 60-75 years. Endpoints were body composition, and physical performance. Randomization resulted in reasonable well-balanced groups, 153 (76%) women completed the trial. Compliance was good (plasma genistein levels 55 +/- 101 and 1259 +/- 1610 nmol/L for placebo and soy group, respectively). The changes in the endpoints during the intervention period among the two intervention groups were analyzed. RESULTS: Body mass index (BMI) and waist-to-hip ratio did not change during intervention. Handgrip strength at the final visit was slightly worse in the soy group compared to the placebo group (-0.45 kg (95% C.I.: -2.5, 1.6 kg; p = 0.7), but this difference was not statistically significant. Self-reported functional status, mobility and physical performance, all slightly improved during intervention but there were no differences between the groups. CONCLUSIONS: The results of the present trial do not support the view that soy isoflavones have favorable effects on body composition and physical performance in postmenopausal women.     

Detection and delineation of an unusual 17p11.2 deletion by array-CGH and refinement of the Smith–Magenis syndrome minimum deletion to 650 kb

Smith–Magenis syndrome (SMS) is a multiple congenital anomaly/mental retardation syndrome and it is characterized by an interstitial deletion of chromosome 17p11.2. SMS patients have a distinct phenotype which is believed to be caused by haploinsufficiency of one or more genes in the associated deleted region. Five non-deletion patients with classical phenotypic features of SMS have been reported with mutations in the retinoic acid induced 1 (RAI1) gene, located within the SMS critical interval. Happloinsufficiency of the RAI1 gene is likely to be the responsible gene for the majority of the SMS features, but other deleted genes in the SMS region may modify the overall phenotype in the patients with 17p11.2 deletions. SMS is usually diagnosed in the clinical genetic setting by FISH analysis using commercially available probes. We detected a submicroscopic deletion in 17p11.2 using array-CGH with a resolution of approximately 1 Mb in a patient with the SMS phenotype, who was not deleted for the commercially available SMS microdeletion FISH probe. Delineation of the deletion was performed using a 32K tiling BAC-array, containing 32,500 BAC clones. The deletion in this patient was size mapped to 2.7 Mb and covered the RAI1 gene. This case enabled the refinement of the SMS minimum deletion to 650 kb containing eight putative genes and one predicted gene. In addition, it demonstrates the importance to investigate deletion of RAI1 in SMS patients.     

Stimulation of regulatory T cell circuits by immunoglobulin-dependent structures on activated B cells

An immunoregulatory circuit is described in which B cell blasts activate syngeneic Ly-1⁺2^?3^? T cells to (a) start a reaction which is indistinguishable from a graft-vs.- host reaction (syngeneic GvH) and (b) induce suppressor cell activity which abrogates the syngeneic GvH. Since capping the surface immunoglobulin (Ig) on B cell blasts blocks their ability to activate this circuit, it is likely that the relevant cell surface structure “seen” on the B cell by the Ly-1 T cell is either Ig itself or another molecule in association with Ig.     

Predictors of HIV Risk Among College Students: A CHAID Analysis1

SUMMARY The purpose of this study was to identify predictors of risk behaviors among college students and to determine how students differed in HIV risk practices. Participants were from six colleges and universities in a large southeastern metropolitan area. The present analysis was limited to participants who were 18 to 25 years of age; single; White, African American, or Asian; and reported initiation of sexual intercourse. The results demonstratedsignificant associations of gender and race with having sex within the past3 months, number of partners, condom use, length of time one knew one's sexual partner, substance use, and asking one's partner about sexualhistory. Using Chi-Square Automatic Interaction Detection (CHAID), the strongest predictor of condom use was noted to be gender, and the strongest predictor of number of partners was race. The findings of this study indicate that HIV risk factors vary dependingon a college student's ethnicity, gender, academic status, and substanceuse. Most importantly, African American men, particularly men who use drugs, and White and Asian men who use alcohol tend to report higher numbers of sexual partners. Females, particularly upperclass White females, and White men who do not use alcohol report infrequent condom use. These findings areuseful for health educators who have begun to recognize the importance ofconsidering the HIV risk factors of students and incorporating informationrelated to these factors into HIV prevention programs. From the results ofthis study, we have several suggestions that health educators and researchersmay want to consider when developing programs for college students: 1. Although students may not need extensive information about basic HIVfacts, they may need reinforcement of the information. In particular, students need to be made aware that lambskin condoms do not offer protection against HIV transmission. 2. Females need to be encouraged and taught the skills to negotiate theuse of and to actually use condoms. These skills need to be reinforced throughout college, particularly as women adopt other methods of birth control (i.e., the pill). 3. The general acceptance of condom use among African Americans and Asians may be a useful tool for the health educator. Promoting and reinforcingthis norm and behavior, while addressing some of the other risk factors inthese groups, may be a particularly effective approach to HIV prevention. 4. For White students whose condom use rates are lower, messages can include the use of condoms for STD and pregnancy protection. Messages for male students could include control over preventing pregnancy or sharing control for pregnancy prevention. 5. Couples often abandon using condoms when they feel they know each other “well enough.” Some guidelines for when to give up condoms might also be given to provide couples with responsible and realistic directions for minimizing their risk when choosing to engage in unprotected sex. These guidelines would include HIV testing two times at least 6 months apart, no evidence of STDs in either partner, and a commitment of both partners to a monogamous relationship. 6. When addressing the number of sexual partners as a risk factor, African American men and women may hold the greatest potential for change, given the greater likelihood of multiple partners in these groups. 7. With respect to drug and alcohol use, health educators may want to include discussions about the influence of drugs (particularly for African American students) and alcohol (particularly for White and Asian students) on inhibiting logical decision-making as it relates to sexual intercourse.     

Associations Between Thyroid Hormone Levels and Urinary Concentrations of Bisphenol A,F, and S in 6-Year-old Children in Korea

ObjectivesBisphenol A (BPA) is used in the electrical, mechanical, medical, and food industries. Previous studies have suggested that BPA is an endocrine disruptor. Regulation of BPA has led to increased use of bisphenol F (BPF) and bisphenol S (BPS). However, few studies have investigated the associations of BPF and BPS with thyroid dysfunction in children. Our study investigated the associations of prenatal BPA and early childhood BPA, BPF, and BPS exposure with thyroid function in 6-year-old children.MethodsPrenatal BPA concentrations were measured during the second trimester of pregnancy in an established prospective birth cohort. We measured urinary BPA, BPF, and BPS concentrations and thyroid hormone levels (thyroid-stimulating hormone, total T₃, and free T₄) in 6-year-old children (n=574). We examined the associations between urinary bisphenol concentrations and percentage change of thyroid hormone concentrations using multivariate linear regression. We also compared thyroid hormone levels by dividing the cohort according to BPA, BPF, and BPS concentrations.ResultsThe associations between prenatal BPA and total T₃ levels were statistically significant in all models, except for girls when using a crude model. The associations between urinary BPA and BPS concentrations and levels of all thyroid hormones were not statistically significant. However, we observed that lower free T₄ levels (−1.94%; 95% confidence interval, −3.82 to −0.03) were associated with higher urinary BPF concentrations in girls only.ConclusionsOur findings identified significant associations between prenatal BPA exposure and total T₃ levels in all children and between BPF exposure and free T₄ levels in girls only.     

Altersspezifische Trends des risikoreichen Alkoholkonsums in Deutschland: Parallele oder unterschiedliche Verläufe?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Nach der Collectivity-of-Drinking-Cultures-Theorie von Skog finden Veränderungen des Alkoholkonsums in allen...     

Two-stage Study of Familial Prostate Cancer by Whole-exome Sequencing and Custom Capture Identifies 10 Novel Genes Associated with the Risk of Prostate Cancer

BackgroundFamily history of prostate cancer (PCa) is a well-known risk factor, and both common and rare genetic variants are associated with the disease.ObjectiveTo detect new genetic variants associated with PCa, capitalizing on the role of family history and more aggressive PCa.Design, setting, and participantsA two-stage design was used. In stage one, whole-exome sequencing was used to identify potential risk alleles among affected men with a strong family history of disease or with more aggressive disease (491 cases and 429 controls). Aggressive disease was based on a sum of scores for Gleason score, node status, metastasis, tumor stage, prostate-specific antigen at diagnosis, systemic recurrence, and time to PCa death. Genes identified in stage one were screened in stage two using a custom-capture design in an independent set of 2917 cases and 1899 controls.Outcome measurements and statistical analysisFrequencies of genetic variants (singly or jointly in a gene) were compared between cases and controls.Results and limitationsEleven genes previously reported to be associated with PCa were detected (ATM, BRCA2, HOXB13, FAM111A, EMSY, HNF1B, KLK3, MSMB, PCAT1, PRSS3, and TERT), as well as an additional 10 novel genes (PABPC1, QK1, FAM114A1, MUC6, MYCBP2, RAPGEF4, RNASEH2B, ULK4, XPO7, and THAP3). Of these 10 novel genes, all but PABPC1 and ULK4 were primarily associated with the risk of aggressive PCa.ConclusionsOur approach demonstrates the advantage of gene sequencing in the search for genetic variants associated with PCa and the benefits of sampling patients with a strong family history of disease or an aggressive form of disease.Patient summaryMultiple genes are associated with prostate cancer (PCa) among men with a strong family history of this disease or among men with an aggressive form of PCa.     

Risk Factors and Management of Leukopenia After Kidney Transplantation: A Single-Center Experience

BackgroundLeukopenia is a common complication after kidney transplantation. The etiology is multifactorial, with medication adverse effects and cytomegalovirus infection as main causes. Optimal strategies to prevent or treat posttransplant leukopenia remain unknown. We aimed to identify risk factors for leukopenia and to investigate the benefit of switching the immunosuppressive therapy to hydrocortisone as a continuous infusion.MethodsWe retrospectively evaluated all patients with leukopenia after kidney transplantation between 2007 and 2017 at our center relative to age- and sex-matched controls.ResultsLeukopenia was associated with the degree of rejection therapy before leukopenia, the immunosuppressive therapy before transplantation, and an induction therapy with rabbit antithymocyte globulin. Patients with leukopenia exhibited increased mortality, an increased incidence of bacterial and viral infections, and more acute rejections. Switching to hydrocortisone as a continuous infusion in patients with severe leukopenia decreased the duration of leukopenia and the incidence of subsequent viral infections, especially with cytomegalovirus.ConclusionLeukopenia is a risk factor for infectious complications and mortality, and it is associated with acute rejection. Switching immunosuppressive therapy to hydrocortisone as a continuous infusion is a safe approach to reduce the duration of leukopenia and the incidence of viral infections.