T cell vaccination in multiple sclerosis: results of a preliminary study

Myelin basic protein (MBP)-reactive T cells are potentially involved in the pathogenesis of multiple sclerosis (MS), and can be depleted by subcutaneous inoculations with irradiated autologous MBP-reactive T cells (T cell vaccination). This preliminary open label study was undertaken to evaluate whether depletion of MBP-reactive T cells would be clinically beneficial to patients with MS. Fifty-four patients with relapsing-remitting (RR) MS (n=28) or secondary progressive (SP) MS (n=26) were immunized with irradiated autologous MBP-reactive T cells and monitored for changes in rate of relapse, expanded disability scale score (EDSS) and MRI lesion activity over a period of 24 months. Depletion of MBP-reactive T cells correlated with a reduction (40 %) in rate of relapse in RR-MS patients as compared with the pre-treatment rate in the same cohort. However, the reduction in EDSS was minimal in RR-MS patients while the EDSS was slightly increased in SP-MS patients over a period of 24 months. Serial semi-quantitative MRI examinations suggest stabilization in lesion activity as compared with baseline MRI. The findings suggest some potential clinical benefit of T cell vaccination in MS and encourage further investigations to evaluate the treatment efficacy of T cell vaccination in controlled trials. Received: 27 November 2000, Received in revised form: 10 May 2001, Accepted: 11 June 2001     

Epilepsy,occipital calcifications,and oligosymptomatic celiac disease in childhood

The association of epilepsy, occipital calcifications, and celiac disease has been recognized as a distinct syndrome. The objective of this study was to present the clinical, electrophysiologic, and neuroradiologic features in a series of patients with this syndrome. Thirty-two patients with the constellation of epilepsy, occipital calcifications, and celiac disease were identified in our epilepsy clinic. The mean age was 11 years and the mean length of follow-up was 7.4 years. The 1990 criteria of the European Society of Pediatric Gastroenterology and Nutrition were used to diagnose celiac disease. The Kruskal-Wallis statistics test was employed with a signficance of P < .05. Thirty-one patients had partial seizures, 21 of them with symptoms related to the occipital lobe. In most patients, the epilepsy was controlled or the seizures were sporadic. Three developed severe epilepsy. Occipital calcifications were present in all cases. Computed tomography in 7 patients showed hypodense areas in the white matter around calcifications, which decreased or disappeared after a period of gluten-free diet in 3 patients. A favorable outcome of epilepsy was detected in patients with the earliest dietary therapy. This study presents the largest series of children with this syndrome outside Italy. White-matter hypodensities surrounding calcifications are rarely reported. A prompt diagnosis of celiac disease might improve the evolution of the epilepsy and may improve cognitive status.     

Do testosterone levels relate to aggression in elderly men with dementia?

The aim of this study was to determine if testosterone and estrogen levels correlate with aggression in older men with dementia. Plasma total and free testosterone and estrogen levels and scores for behavioral disturbances, in particular aggression, were measured in 50 elderly males who had a diagnosis of dementia. Aggression was analyzed separately from agitation. Pearson correlations were calculated to determine the association between testosterone and estrogen and aggression. Linear regression analyses determined the influence of hormone levels on aggression, controlling for age, medical burden, and dementia severity. Free testosterone levels showed significant positive correlations with measures of aggression. Estrogen levels showed significant negative correlations with measures of aggression.     

Mammography uptake predictors in older women

BACKGROUND: In women aged under 65 years, socio-economic factors and general health behaviours are important predictors of mammography uptake. Little is known about whether these factors are important in older women. OBJECTIVE: To examine a broad range of mammography uptake predictors in women aged 65 and older registered with a London (UK) practice. METHODS: A survey of all female patients aged 65 and over (n = 613) in a south London practice included questions on mammography and cervical screening, general health and functional ability, socio-economic factors, mental health, health behaviours, and attitudes to health. Associations between mammography uptake and other factors were examined using logistic regression. RESULTS: The response rate was 70% (432/613). Increased age was strongly associated with decreased mammography uptake. Additionally, socio-economic factors and general health behaviours (previous cervical smear, drinking alcohol and being a non-smoker) were independently predictive of mammography uptake. Measures of physical and mental health and health attitudes were not independent predictors. Restricting analyses to the oldest women, outside the national screening programme, gave very similar results. CONCLUSIONS: In this sample of older women, socio-economic factors and general health behaviours were more predictive of mammography uptake than measures of physical and mental health or attitudes to health. Knowledge of these predictors is of increasing importance as the screening programme in the UK is extended up to age 70.     

Promoting Healthy Lifestyles: Alternative Models' Effects (PHLAME)

The Promoting Healthy Lifestyles: Alternative Models' Effects (PHLAME) study evaluates the efficacy of two intervention strategies for improving nutrition and physical activity practices in fire fighters: a team-centered program and a one-on-one format targeting the individual. PHLAME compares these two behavior change models (the team-based versus the one-on-one approaches) against a usual-care control group. As a group, fire fighters have a concentration of the same harmful behaviors and health risks commonly afflicting the US population. Fire fighters have a unique work structure which is ideal for a team-centered model of behavior change. This strategy, based on Social Learning Theory, focuses on a team of fire fighters who work together on the same shift. If this team-centered model proves successful, it could provide a cost-effective method to impact behavior, and be disseminated among fire bureaus and in other team settings. The one-on-one intervention incorporates the Transtheoretical Model of behavior change, uses Motivational Interviewing for its counseling strategy and could be used in the more typical provider-client clinic setting. Findings from PHLAME will provide information about the process and outcomes of these models' ability to achieve health behavior change.     

Time trends incidence of both major histologic types of esophageal carcinomas in selected countries, 1973-1995

The purpose of our study was to examine the incidence patterns of 2 major histologic types of esophageal cancer, in selected countries world-wide and to identify components of birth cohort, period and age as determinants of observed time trends using regression modeling. The roles of temporal changes in specification of histology of tumors and of classification of cancers at the gastroesophageal junction as esophageal or gastric in origin were taken into consideration. In all, 56,426 esophageal cancer cases were included. The results indicate that the incidence rate of squamous cell carcinoma of the esophagus has been relatively stable in most of the countries analyzed, although increasing trends were observed in Denmark and the Netherlands (Eindhoven) among men and in Canada, Scotland and Switzerland among women. There was a significant increase in the incidence of esophageal adenocarcinomas in both sexes in the United States (among whites and blacks), Canada and South Australia and in 6 European countries (Scotland, Denmark, Iceland, Finland, Sweden and Norway). In France the increase was limited to men and in Switzerland the increase was observed only in women. Modeling was unable to distinguish which trends were the results of changes in risk between generations (as cohort effects), or changes in all age groups simultaneously (as a period effect).     

Differential expression and biodistribution of cytokeratin 18 and desmoplakins in non-small cell lung carcinoma subtypes

Adenocarcinoma (AC), squamous cell carcinoma (SCC) and adenosquamous carcinoma (ASC) of the lung are morphologically distinguished in part by cyto-architectural features. However, little is known about the relative expression and distribution of cyto-architectural proteins among AC, SCC and ASC. Initial microarray analysis revealed significant differences in expression of two cyto-architectural genes in AC, SCC and ASC. Desmoplakin (DP) 1 and 2, which link desmosomes to intermediate filaments, was strongly expressed in SCC relative to AC and ASC. Cytokeratin 18 (CK18), an intermediate filament that is commonly linked to desmoplakin, was strongly expressed in AC and ASC relative to SCC. Western blot analysis demonstrated that AC and ASC had abundant CK18 protein, whereas CK18 was weakly detected in SCC. DP 1 and 2 are strongly expressed in SCC and minimally expressed in AC and ASC. However, the ratio of one to the other is the same in SCC and AC, but DP2 is lost in ASC. Microscopic analysis with fluorescence-labeled antibodies for CK18 and DP 1 and 2 revealed abundant membrane localization of DP and minimal perinuclear localization of CK18 in SCC. In contrast, in both AC and ASC, the CK18 protein was diffusely distributed within the cytoplasm, and DP showed both membranous and cytoplasmic localization. In conclusion, the data here shows that AC, SCC and ASC each have specific patterns of DP 1 and 2 and CK18 gene expression, protein content and biodistribution.     

Molecular follow-up of preneoplastic lesions in bronchial epithelium of former Chernobyl clean-up workers

Ionizing radiation is a potent lung carcinogen, but the precise molecular damage associated with it is still unknown. In this study we investigated cancer-related molecular abnormalities including K-ras (codon 12) mutation, p16(INK4A) promoter hypermethylation and microsatellite alterations at seven chromosomal regions in successive biopsies obtained from former Chernobyl cleanup workers in comparison with smokers and nonsmokers who have never had radiation exposure. Our results indicate that prolonged persistence of inhaled radioactive particles is associated with appearance of allelic loss at 3p12, 3p14.2 (FHIT), 3p21, 3p22-24 (hMLH1) and 9p21 (p16INK4A) in bronchial epithelium of former Chernobyl clean-up workers. The prevalence of 3p14.2 allelic loss was associated with decreased expression of the FHIT mRNA in their bronchial epithelium in comparison with control group of smokers. During several years of our monitoring samples of epithelium were collected from the same area of bronchial tree. In epithelium exposed to carcinogens (tobacco smoke and/or radioactivity) the total number of molecular abnormalities was significantly higher in dysplasia and in morphologically normal foci progressed later to dysplasia than in these samples which never showed evidence of such progression. Our findings indicate that extensive cancer-related molecular abnormalities sequentially occur in radiation damaged bronchial epithelium of former Chernobyl clean-up workers.