A phase II study of the survivin suppressant YM155 in patients with refractory diffuse large B-cell lymphoma

BACKGROUND:

Few effective therapeutic options exist for patients with refractory diffuse large B‐cell lymphoma (DLBCL). YM155 is a survivin suppressant with activity against DLBCL in a phase I trial. This phase II study was conducted to better characterize the toxicity and efficacy of this small molecule in patients with refractory DLBCL.

METHODS:

Forty‐one patients with a median age of 66 years and 3 prior regimens were enrolled and treated with a YM155 dose of 5 mg/m²/d by continuous infusion for 168 hours every 21 days for up to 15 cycles of treatment. The median number of completed cycles was 3.

RESULTS:

One patient had a complete remission (CR) (2.4%) with an additional 2 patients (5.9%) responding, with a median progression‐free survival of 58 days.

CONCLUSIONS:

YM155 was well tolerated with major toxicities including anemia and fatigue. Whereas YM155 had limited single‐agent activity, preclinical data suggest its role in combination with other agents, including rituximab, and a study of that combination in ongoing. Cancer 2012;118: 3128–34. © 2011 American Cancer Society.     

Long-term effects of serum cholesterol on bone mineral density in women and men: the Framingham Osteoporosis Study

Laboratory studies have suggested a role for cholesterol in the pathogenesis of both osteoporosis and atherosclerosis. The purpose of this prospective study was to assess whether cholesterol levels, repeatedly measured over three decades in young and middle-aged adult women and men, predicted bone mineral density (BMD) at advanced age. Study participants included 712 women and 450 men enrolled in the Framingham Osteoporosis Study, aged 32-61 years at baseline (1953-55) who underwent bone densitometry 34 years later (1988-1989). BMD was measured at the proximal femur (neck, trochanter, and Ward's triangle) and lumbar spine using dual-photon absorptiometry and at the one-third radial shaft and ultradistal radius using single-photon absorptiometry. Sex-specific multivariable linear regression was used to model each BMD site as a function of total cholesterol level, adjusted for age, cigarette smoking, alcohol consumption, body mass index, systolic blood pressure, diabetes, and estrogen use (women). No significant association between total cholesterol and BMD was found in women for any of the bone sites considered. For example, adjusted mean BMD at the lumbar spine was similar in women from the lowest to highest quartile of total cholesterol, respectively, 1.07, 1.08, 1.06, 1.07 g/cm2; P for trend=0.98. Similarly, the findings in men largely showed no association between cholesterol and BMD, although there was an isolated finding of a statistically significant trend in decreasing mean radial shaft BMD with increasing total cholesterol, 0.73, 0.72, 0.72, 0.70 g/cm2, lowest to highest quartile, P for trend=0.02. Cholesterol levels in women and men from young adulthood to middle age years do not appear to have long-term clinical implications for osteoporosis later in life.     

Severe combined immunodeficiency: a cohort of 40 patients.

Severe Combined Immunodeficiency (SCID) consists of a heterogeneous group of genetic disorders characterized by an arrest in T lymphocyte development which is variably associated with an abnormal differentiation of B and NK cells. In order to depict the clinical state of Iranian patients with SCID, records of forty patients were reviewed. Patients were classified based on the flow cytometry data in two groups of B- and B+. In thirty two families (80%) parents were consanguine and in 17 families (50%) there were affected members other than proband. We showed that autosomal forms of SCID might be more frequent due to higher rate of consanguineous marriages. Alongside several infective complications, complicated Bacillus Calmette-Guérin (BCG) vaccination was documented in 18 cases (45%) following the routine vaccination at birth. BCG immunization is still a part of standard vaccination for newborns in developing countries; whereas in communities with a better health condition it could be held for a few months and performed for kids whose immune system sounds intact. We discuss where consanguine mating is common, a test of screening should be run timely. A complete blood count of cord blood could reveal lymphocytopenia at birth; this helps early diagnosis. Genetic consultation would help the families with affected members preventing new SCID offspring.     

Heterogeneity in the prevalence of methylenetetrahydrofolate reductase gene polymorphisms in women of different ethnic groups

OBJECTIVE: To determine the prevalence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms in women of different ethnic groups and to relate these common mutations to plasma homocysteine, red cell folate, and serum folate. DESIGN: A one-time fasting blood sample was obtained for MTHFR genotype (C677T and A1298C) determinations (n=433). Serum folate, red cell folate, and homocysteine analyses were performed in nonfolic acid supplement users (n=215). SUBJECTS/SETTING: This study involved 433 women from four ethnic groups, including 193 Hispanic women of Mexican descent, 139 white women, 53 Asian women of mixed descent, and 48 African American women. STATISTICAL ANALYSIS PREFORMED: Chi;(2), t Test, and analysis of variance were used. RESULTS: Mexican women (18.1%) had a higher frequency of the 677 TT genotype compared with white (7.2%), Asian (3.8%), and African American (0%) women. White women (7.9%) had a higher frequency of the 1298 CC genotype than the other ethnic groups (range=1.9% to 2.6%). The frequency of compound heterozygosity (677 CT + 1298 AC) was higher in Mexican (17.6%) and white (15.1%) women than Asian and African American ( approximately 4% to 6%) women. In the era of folic acid fortification, neither genotype, independently or together, was associated with homocysteine or blood folate concentrations when ethnic groups were combined. In Mexican women, however, a linear trend (P相似文献   

The Role of Immigrant Admission Classes on the Health and Well-being of Immigrants and Refugees in Canada: A Scoping Review

Many countries offer different pathways through which migrants can enter a new country. In Canada, there are three main immigrant admission classes: economic, family, and refugee. Previous research suggests that there are differences in health outcomes among various subgroups of migrants. A scoping review was conducted to characterize the role of immigrant admission classes on the health and well-being of immigrants and refugees in Canada. MEDLINE, Embase, PsycINFO, Sociological Abstracts, and EconLit databases were searched for quantitative studies published in English after 1990. The screening and selection process identified 27 relevant studies. Studies were categorized into four key reported outcomes: health care and services utilization, self-rated health and mental health, medical conditions and chronic illnesses, and social integration and satisfaction. Findings confirm that certain subgroups have worse health outcomes after arrival, particularly refugees, family class and other dependent immigrants. Health outcomes vary significantly across immigrant subgroups defined by the admission class through which they entered Canada.

     

The Taxonomy of Everyday Self-management Strategies (TEDSS): A framework derived from the literature and refined using empirical data

Objective

To extend our understanding of self-management by using original data and a recent concept analysis to propose a unifying framework for self-management strategies.

Effects of diode and erbium lasers as an adjunct to scaling and root planing on clinical and immunological parameters in non-surgical periodontal treatment: a split-mouth randomized controlled clinical trial—“effects of lasers on immunological parameters”

Lasers in Medical Science - This study evaluated the effects of diode and erbium lasers, as an adjunct to scaling and root planing (SRP), on clinical and immunological parameters in non-surgical...