Thermal and metabolic responses of sleep deprivation of humans during acute cold exposure

PURPOSE: This investigation evaluated the effects of 33 h of sleep deprivation on the thermoregulation in 12 male and female subjects (26.6 +/- 6.4 yrs) during 180 min of cold exposure in 12 degrees C air. METHODS: Subjects underwent two cold air trials (CAT): one following a normal night of sleep (i.e., 6-8 h) (CON); and one following 33 h of sleep deprivation (SDEP). Rectal temperature (Tre), mean skin temperature (Tsk), heat production (HP), and tissue insulation (Iti), were measured at 5, 15, 30, and every 30 min thereafter. RESULTS: ANOVA revealed no significant differences (p > 0.05) between CON and SDEP for Tre, Tsk, HP, and Iti. A main effect for time was demonstrated for Tre, Iti, HP, and Tsk. A trial x time interaction for Tre and Tsk (p = 0.021) was demonstrated. DISCUSSION: Significant interactions were demonstrated for Tre and Tsk, but post hoc analysis determined no differences between SDEP and CON. This may have been due to the length of the sleep deprivation, cold stressor, or a combination of the two. There were also no overall differences in HP or Iti between SDEP and CON. Further research in this area is needed to evaluate the effects of sleep deprivation during acute cold exposure.     

Possible therapy for age-related macular degeneration using human telomerase

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in people over 60 years of age in the US and many other developed countries. Increasingly sophisticated methods for the diagnosis and treatment of macular degeneration are not effective for the majority of patients in whom late stage disease is present at the time of diagnosis. Research to elucidate the changes in RPE cell biology during aging has stimulated interest in preventive and prophylactic therapies for earlier intervention in the degenerative process. In the normal retina, the RPE performs the functions of barrier, macrophage, and neuroprotective cell layer. During aging and in the presence of disease the robustness of each of these functions diminishes. The utility of telomerase-mediated cell and gene therapy to prevent the decline in function of RPE cells during aging is evaluated.     

Mucin core peptide expression can help differentiate Barrett's esophagus from intestinal metaplasia of the stomach

It is important to distinguish Barrett's esophagus (BE) from intestinal metaplasia related to carditis because these conditions have a different natural history, risk of malignancy, and treatment. However, the distinction between these entities is difficult both clinically and pathologically. The aim of this study was to evaluate and compare the immunostaining pattern of five mucin core polypeptides in BE to cases of carditis or antritis with intestinal metaplasia. Routinely processed mucosal biopsies from 22 patients with intestinal-type BE, 24 patients with cardia intestinal metaplasia (10 Helicobacter pylori positive), 17 patients with antral intestinal metaplasia (all H. pylori positive), 20 control patients with a normal antrum, and 22 control patients with a normal cardia were immunostained with monoclonal antibodies against MUC1, MUC2, MUC3, MUC5AC, and MUC6 mucin core polypeptides. Staining was evaluated separately for goblet cells and non-goblet columnar cells and compared between all groups. A significantly higher number of BE cases (P < 0.05) showed goblet cell staining for MUC1 (55%) or MUC6 (32%) compared with patients with carditis with intestinal metaplasia (MUC1 14%, MUC6 7%) or antritis with intestinal metaplasia (MUC1 6%, MUC6 0%). BE also showed a higher frequency of MUC1 and MUC6 positivity in non-goblet columnar cells compared with carditis and antritis cases with intestinal metaplasia. Only cases of BE showed combined MUC1 and MUC6 staining (sensitivity 23%, specificity 100%). The sensitivity and specificity of MUC1 staining for BE are 55% and 96%, respectively, and for MUC6 staining 30% and 96%, respectively. Interestingly, normal gastric cardia mucosa also showed a significantly higher prevalence of MUC2 and MUC3 expression in glandular epithelium (29% and 38%, respectively) compared with the antrum (0% for both markers) (P < 0.05). In conclusion, MUC1 and MUC6 expression in BE is distinct from that of the cardia and antrum with intestinal metaplasia; thus, immunophenotyping for these markers may have some value in a subset of patients in helping to separate BE from patients with intestinal metaplasia of the cardia. Columnar epithelium in the "normal" gastric cardia has a partially intestinalized phenotype and, as a result, may represent an early form of metaplastic epithelium.     

Pathologic features of reflux and Helicobacter pylori-associated carditis: a comparative study

Inflammation of the gastric cardia, which is the most proximal portion of the stomach, in most instances is the result of either gastroesophageal reflux disease or H. pylori infection. Histologic distinction between these two entities is important because the treatment, natural history, and risk of malignancy are different. Moreover, multilayered epithelium, a possible precursor to Barrett's esophagus, has only recently been described in the gastric cardia, and its relationship to gastroesophageal reflux disease is unknown. The aim of this study was to compare the histologic features of the gastric cardia and the prevalence of multilayered epithelium in patients with reflux versus H. pylori-associated carditis. Routinely processed hematoxylin and eosin-stained mucosal biopsies of the gastric cardia from 30 patients with reflux-associated carditis, 25 with H. pylori-associated carditis, and 30 control patients (no reflux, no H. pylori) were evaluated for a wide variety of histologic features such as goblet cell metaplasia, presence of multilayered epithelium, type of glandular epithelium (mucous, oxyntic, mixed mucous/oxyntic), pancreatic metaplasia, overall degree of inflammation, and the quantity of individual types of inflammatory cells. The clinical and histologic features were compared between the two study groups and controls. Clinically, the reflux carditis group (male/female ratio: 21/9, mean age 56 years) had a significantly higher male/female ratio (p <0.01) and a slightly higher mean age in comparison with the H. pylori group (male/female ratio: 9/16, mean age 50 years). Histologically, the reflux group had significantly less overall inflammation (p <0.05), with fewer plasma cells (p <0.04) and neutrophils (p <0.006), but a higher prevalence of multilayered epithelium [9 of 30 (30%) vs 1 of 25 (4%) in the H. pylori group, p = 0.01]. In the reflux carditis group, multilayered epithelium was significantly associated with neutrophilic inflammation (p <0.05), but not any other features of chronic carditis or with any of the specific epithelial cell types. The control group showed less inflammatory activity in comparison with the H. pylori group and a lower prevalence of multilayered epithelium and eosinophilic inflammation in comparison with the reflux group. The clinical and pathologic features of reflux carditis are distinct from H. pylori carditis and are characterized by less overall inflammation and fewer neutrophils and plasma cells. Multilayered epithelium not uncommonly occurs in the cardia of patients with gastroesophageal reflux disease but without Barrett's esophagus, further supporting our hypothesis that multilayered epithelium may represent an early precursor in the development of columnar metaplasia in Barrett's esophagus.     

Severe acute respiratory syndrome: radiographic review of 40 probable cases in Toronto,Canada

PURPOSE: To review radiographic findings of patients with probable severe acute respiratory syndrome (SARS) who were seen at a University of Toronto (Ontario, Canada) teaching hospital. MATERIALS AND METHODS: Findings were reviewed for 40 patients who fulfilled the World Health Organization criteria for probable SARS. A template was designed for the analysis of each serial radiograph to observe patterns and distribution of disease, interval changes, and complications. The majority of radiographs were anteroposterior views. A clinical database of these patients was also collected for clinical-radiologic comparison. RESULTS: The mean age of the patients (18 male, 22 female) was 42.7 years. Patients had a normal chest radiograph and focal, multifocal, and/or bilateral consolidation. The pattern of consolidation tended to be peripheral and poorly marginated and involved middle and lower lung zones. The serial sequence fell into two major subgroups, which correlated closely with clinical outcome. Consolidation in one group cleared within a matter of days, while the second group went on to develop rapid and extensive bilateral pneumonia, with a prolonged hospital stay. Subsegmental atelectasis and pleural complications were rarely observed. CONCLUSION: SARS pneumonia can manifest as focal peripheral consolidation that clears relatively quickly and does not cause secondary complications or that progresses to bilateral consolidation and a more protracted clinical course.     

The analysis of survival data with a non-susceptible fraction and dual censoring mechanisms

It is known that the ages of onset of many diseases are determined by both a genetic predisposition to disease as well as environmental risk factors that are capable of either triggering or hastening the onset of disease. Difficulties in modelling onset ages arise when a large fraction fail to inherit the disease-causing gene, and multiple reasons for censoring result in unobserved onset ages. We present a parametric Bayesian model that includes subjects with missing age information, non-susceptible subjects and allows for regression on risk factor information. The model is fit using Markov chain Monte Carlo simulation from the posterior distribution, and allows the simultaneous estimation of the proportion of the population at risk of disease, the mean onset age of disease, survival after disease onset, and the association of risk factors with susceptibility, onset age and survival after onset. An example employing Huntington's disease data is presented.     

Age effects on thermal, metabolic, and perceptual responses to acute cold exposure

INTRODUCTION: Thermoregulatory accidents rank as the sixth leading cause of death among older adults. Therefore, there is an urgency to clarify the influence of age on thermoregulation. This investigation sought to evaluate the influence of age on the thermal, metabolic, and perceptual responses of healthy, physically active, old (OLD) and young (YNG) men during exposure to 12, 18, and 27 degrees C for 120 min. METHODS: There were four old (67.7 +/- 4.6 yr) and four young (26.7 +/- 3.4 yr) adult men who participated. Following a baseline period (30 min), the subjects, wearing only cotton shorts, were moved into an environmental chamber where they remained seated for 120 min or until rectal temperature (Tre) was < or = 35 degrees C. Data were collected for Tre, mean skin temperature (Tsk), oxygen consumption (Vo2), tissue insulation (I), thermal sensation (TS), and heat production (HP). RESULTS: Analysis of variance demonstrated a significant (p < 0.05) time x group interaction for Tre, HP, and I, whereby Tre, HP and I were higher in the YNG vs. OLD. Also, Tsk differed between YNG and OLD with the OLD exhibiting a higher Tsk. TS did not differ, although subjects reported feeling colder with each trial. DISCUSSION: These data suggest that there may be a differential thermoregulatory response between OLD and YNG individuals. The higher Tsk in the OLD suggests a deficit in the peripheral response leading to an increased heat loss over a protracted period of time. This heat loss may contribute to the reduction in core temperature and to the development of hypothermia in the older adult.     

Effects of dietary selenium supplementation on DNA damage and apoptosis in canine prostate

The trace mineral selenium inhibits cancer development in a variety of experimental animal models. We used an in vivo canine model to evaluate the effects of dietary selenium supplementation on DNA damage in prostate tissue and on apoptosis in prostate epithelial cells. Sexually intact elderly male beagle dogs were randomly assigned to receive an unsupplemented diet (control group) or diets that were supplemented with selenium (treatment group), either as selenomethionine or as high-selenium yeast at 3 micro g/kg or 6 micro g/kg body weight per day for 7 months. The extent of DNA damage in prostate cells and in peripheral blood lymphocytes, as determined by the alkaline comet assay, was lower among the selenium-supplemented dogs than among the control dogs (prostate P<.001; peripheral blood lymphocytes P =.003; analysis of variance) but was not associated with the activity of the antioxidant enzyme glutathione peroxidase in plasma. The median number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive (i.e., apoptotic) prostate epithelial cells was 3.7 (interquartile range = 1.1-7.6) for the selenium-supplemented dogs and 1.7 (interquartile range = 0.2-2.8) for the control dogs ( P =.04, Mann-Whitney U test). These data suggest that dietary selenium supplementation decreases DNA damage and increases epithelial cell apoptosis within the aging canine prostate.