Reduced tocopherol content of B cells from patients with chronic lymphocytic leukemia

The tocopherol content of lymphocytes, erythrocytes, and plasma from patients with chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and normal subjects was measured by a sensitive high performance liquid chromatographic method. Lymphocytes from patients with CLL had lower values of tocopherol (1.7 +/- 1.0 micrograms/10(9) cells) than lymphocytes from normal subjects (3.8 +/- 0.7 micrograms/10(9) cells). Mononuclear cells from patients with HCL had an increased tocopherol content of 6.2 +/- 1.0 micrograms/10(9) cells. Subfractionation of the lymphocytes from patients with CLL into T- and B-cell subgroups showed that the tocopherol content of T cells was the same as in normal subjects (4.1 +/- 0.5 micrograms/10(9) cells versus 3.5 +/- 1.2), but that the tocopherol content of the B cells was markedly reduced compared to normals (2.6 +/- 1.0 versus 6.0 +/- 1.3).     

Allogeneic bone marrow transplantation with a fixed low number of T cells in the marrow graft [see comments]

Despite prophylaxis with immunosuppressive drugs, severe acute graft- versus-host disease (GVHD) remains a major cause of morbidity and mortality in patients transplanted with unmodified bone marrow (BM) grafts from HLA-identical siblings. Although T-cell depletion of the BM graft has evolved as the most effective method to prevent severe acute GVHD, this beneficial effect is counterbalanced by an increased rate of graft failure and relapse of the disease. To find an approach to T-cell depletion that may avoid these extreme risks, we gave BM recipients a fixed low number of 1 x 10(5) donor T cells per kilogram of recipient's body weight in the graft. This corresponds with 99% T-cell depletion and is achieved by the addition of T cells to the graft that was previously depleted of T cells. A total of 70 patients with hematologic malignancies or aplastic anemia, including 40 patients with standard- risk leukemias, received BM grafts, depleted of T cells according to this approach, from HLA-identical siblings. The preparative regimen consisted of cyclophosphamide and total body irradiation. The patients also received a short course of cyclosporine posttransplant. Graft failure did not occur. Acute GVHD, only grade I or II, was seen in 70% of the patients and was limited to the skin in all patients. Chronic GVHD occurred in 31% of the patients and, with the exception of 1 patient, was limited to the skin as well. Relapse occurred in 3 of 40 (8%) patients with standard-risk leukemias, resulting in a projected survival at 5 years of 80%. Patients with standard-risk diseases had a procedure-related mortality of 11%. Quality of life, determined 1 year after BM transplant, was good in almost all patients with standard-risk diseases. Thus, this approach of T-cell depletion may be an approach that avoids the development of severe acute and chronic GVHD without damaging the function or antileukemic effect of the graft and that has a low transplant-related morbidity and mortality.     

The ECG in sarcoidosis – a marker of cardiac involvement? Current evidence and clinical implications

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas. Cardiac involvement is often limiting patients’ prognosis. Cardiac sarcoidosis can manifest with variant cardiac arrhythmias, of which atrioventricular (AV)-block-related bradycardia and ventricular tachycardias are the most common. Although cardiac sarcoidosis remains a histopathological diagnosis, the significance of imaging modalities, especially cardiac magnetic resonance imaging is increasing rapidly but mainly remains reserved for patients with a high suspicion due to a previous arrhythmia or unknown cardiomyopathy. Thus, there is a need for screening in daily clinical practice so that possible characteristic electrocardiographic (ECG) findings may guide the way to detect the disease.We therefore evaluated the ECG as a potential tool for screening of cardiac sarcoidosis and present different electrophysiological manifestations of cardiac sarcoidosis based on a literature review.The ECG is a valuable tool for screening of cardiac involvement in patients with sarcoidosis. Several parameters have been shown to be associated with cardiac involvement in sarcoidosis such as higher-degree AV-block, QRS complex fragmentation and widening, as well as certain T wave abnormalities that may indicate cardiac involvement, of which the latter two are most promising and specific. However, prospective studies examining a large number of trials are desirable.     

The opposing roles of NOTCH signalling in head and neck cancer: a mini review

NOTCH signalling can exert oncogenic or tumour suppressive effects in both solid and haematological malignancies. Similar to T‐cell acute lymphoblastic leukaemia (T‐ALL), early studies suggested a pro‐tumorigenic role of NOTCH in head and neck squamous cell carcinoma (HNSCC), mainly based on the increased expression levels of the genes within the pathway. Recently, data from exome sequencing analyses unexpectedly pointed to a tumour suppressor role for NOTCH in HNSCC by identifying loss‐of‐function mutations in the NOTCH1 gene in a significant proportion of patients. These data have questioned the accepted role of NOTCH in HNSCC and the possible rationale of targeting NOTCH in this disease. This review summarises the current information on NOTCH signalling in HNSCC and discusses how this pathway can apparently exert opposing effects within the same disease.     

Relation between aerobic fitness and brain structures in amnestic mild cognitive impairment elderly

Mild cognitive impairment (aMCI) is a clinical condition, with high risk to develop Alzheimer’s disease. Physical exercise may have positive effect on cognition and brain structure in older adults. However, it is still under research whether these influences are true on aMCI subjects with low Ab_42 and high total tau in cerebrospinal fluid (CSF), which is considered a biomarker for AD. Therefore, we aimed to investigate a possible relation between aerobic fitness (AF) and gray matter (GM) volume and AF and white matter (WM) integrity in aMCI with a CSF biomarker. Twenty-two participants with aMCI acquired the images on a 3.0-T MRI. AF was assessed by a graded exercise test on a treadmill. Voxel-based morphometry and tract-based spatial statistic methods were used to analyze the GM volume and WM microstructural integrity, respectively. We correlated AF and GM volume and WM integrity in aMCI (p < 0.05, FWE corrected, cluster with at least five voxels). There was a positive relation between AF and GM volume mostly in frontal superior cortex. In WM integrity, AF was positively correlated with fractional anisotropy and negatively correlated with mean diffusivity and radial diffusivity, all in the same tracts that interconnect frontal, temporal, parietal, and occipital areas (longitudinal fasciculus, fronto-occipital fasciculus, and corpus callosum). These results suggest that aerobic fitness may have a positive influence on protection of brain even in aMCI CSF biomarker, a high-risk population to convert to AD.     

Demographic and clinical predictors of depressive symptoms among incarcerated women

Background  

Imprisonment may lead to the development of mental illness, especially depression. This study examines the clinical and sociodemographic profiles of imprisoned women, identifies indicative signs of depression, and relates these indicators to other variables.     

Using buprenorphine to facilitate entry into residential therapeutic community rehabilitation

For opioid-dependent patients, the need for detoxification has been a barrier to entry into long-term residential treatment. This report describes a retrospective observational cohort study with the first 38 opioid-dependent patients entering First Step, a 14-day buprenorphine-naloxone (Suboxone) detoxification regimen integrated into a long-term residential therapeutic community (TC) program. Eighty-nine percent (34 of 38) of First Step patients completed a 14-day buprenorphine taper protocol, 50% (19 of 38) completed an initial 3- to 4-week stay, and 39% (15 of 38) completed at least 3 months of residential treatment at the TC. Retention did not differ significantly in a demographically matched concurrently admitted control group without impending opioid withdrawal, in which 65% (24 of 37) completed an initial 3- to 4-week stay (p = .20) and 57% (21 of 37) completed at least 3 months of treatment (p = .14). Withdrawal symptoms were mild, and there were no instances of precipitated withdrawal. The findings suggest the potential for buprenorphine to serve as a bridge, improving the viability of long-term residential treatment for managing opioid dependence.     

Cystatin C and carotid intima-media thickness in asymptomatic adults: the Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND: Persons with early kidney disease have an increased risk of cardiovascular events and mortality, but the importance of accelerated atherosclerosis in promoting these outcomes is unclear. We therefore explored whether serum cystatin C level is associated with carotid intima-media thickness (IMT) in ambulatory adults without clinical heart disease. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: We evaluated 6,557 ethnically diverse persons free of clinical cardiovascular disease aged 45 to 84 years at the baseline visit of the Multi-Ethnic Study of Atherosclerosis. PREDICTORS: Kidney function was estimated by using 2 methods: serum cystatin C level and estimated glomerular filtration rate, based on creatinine and cystatin C levels. OUTCOMES & MEASUREMENTS: Study outcomes were internal and common carotid IMT, measured by using high-resolution B-mode ultrasound. Multivariate linear and logistic regressions were used to evaluate the independent association of kidney function with carotid IMT. RESULTS: In unadjusted linear analysis, each SD (0.23 mg/L) greater cystatin C level was associated with 0.091-mm greater internal carotid IMT (P < 0.001), but this association was diminished by 70% after adjustment for age, sex, and race/ethnicity (0.027 mm; P < 0.001) and was no longer significant after adjustment for cardiovascular risk factors (0.005 mm; P = 0.5). Similarly, the strong unadjusted associations of cystatin C level with common carotid IMT disappeared after adjustment. Chronic kidney disease, defined by using either creatinine level or cystatin C-based estimated glomerular filtration rate less than 60 mL/min/1.73 m(2), had no independent association with internal and common carotid IMT. LIMITATIONS: There were few participants with severe kidney disease. CONCLUSIONS: Cystatin C level had no independent association with carotid IMT in a population free of clinical heart disease. This observation suggests that accelerated atherosclerosis is unlikely to be the primary mechanism explaining the independent association of cystatin C level with cardiovascular risk.