An observational study of sun and heat protection during Canada Day outdoor celebration, 2003

Attendance at summer outdoor mass gatherings may lead to heat- and sun-related illness. The purposes of this study were: (1) to estimate the proportion of people in attendance at the 2003 Canada Day celebration in the National Capital Region who used sun and heat protective items; (2) to identify factors associated with the utilization of these protective items; and (3) to provide research data to public outdoor event organizers when developing evidence-based plans for safer events. A naturalistic observational cross-sectional method was used to gather information at the 2003 Canada Day celebration in the National Capital Region on attendees' demographics, the sun and heat protective items they used and the protective resources available at the event sites. Of the 398 observed attendees, the proportion using any one of the protective items ranged from 3 percent (an open umbrella) to 51.5 percent (sunglasses). Females were more likely to use protective items more than males, and adults more likely than children. Planners of public outdoor events should consider the factors that influence the utilization of sun and heat protective behaviours and the environmental modifications that would allow participants to make safe choices.     

Membrane-associated sickle hemoglobin: a major determinant of sickle erythrocyte rigidity

Micropipette aspiration tests on single erythrocytes have previously shown that the static rigidity (membrane shear modulus) of oxygenated sickle cells increased with increasing hemoglobin concentration, whereas the rigidity of normal cells was independent of hemoglobin concentration. Moreover, it was observed that after mechanical extension, sickle cells exhibited persistent deformation more frequently and to a greater extent than normal cells. To ascertain if differences in association of normal and sickle hemoglobin with the membrane could account for these observations, we measured rheologic properties of normal membranes reconstituted with sickle hemoglobin and sickle membranes reconstituted with normal hemoglobin. The static rigidity of normal ghosts reloaded with sickle hemoglobin was higher than those of either normal ghosts reloaded with normal hemoglobin or native normal cells. On the other hand, the increased rigidity of native sickle cells decreased to near-normal values following reconstitution with normal hemoglobin. Furthermore, we observed that normal ghosts reconstituted with sickle hemoglobin exhibited persistent bumps after mechanical extension, but no bumps formed on normal ghosts reconstituted with normal hemoglobin. Moreover residual bumps were not produced on sickle cells reloaded with normal hemoglobin. Since mechanical characteristics peculiar to sickle cells could be induced in normal cells by incorporation of sickle hemoglobin, and since normal characteristics could be restored to sickle cells by incorporation of normal hemoglobin, we suggest that the interaction of sickle hemoglobin with the cell membrane is responsible for augmented static rigidity of oxygenated sickle erythrocytes.     

Expression of CD27 and its ligand, CD70, on chronic lymphocytic leukemia B cells

Crosslinking the CD27 antigen on T cells provides a costimulatory signal that, in concert with T-cell receptor crosslinking, can induce T- cell proliferation and cellular immune activation. We find that chronic lymphocytic leukemia (CLL) B cells from most patients coexpress both membrane-bound and soluble CD27, along with its newly identified ligand, CD70. The expression of soluble CD27 may preclude leukemic B cells from stimulating T cells via CD70, thereby potentially impairing their ability to function as effective antigen-presenting cells. We find that leukemic B-cell expression of soluble and membrane-bound CD27 can be downmodulated through a CD40-dependent signal. This signal also induces enhanced expression of CD70 on both normal and leukemic B cells. We find that tumor necrosis factor (TNF)-alpha, or the Th1 cytokine interferon (IFN)-gamma, also can induce downmodulation of CD27, whereas Th2-associated cytokines interleukin-4 (IL-4) or IL-10 can enhance leukemic B-cell expression of this accessory molecule. The modulation of CD27 induced by these conditions is accompanied by reciprocal changes in the expression levels of CD70, suggesting that these accessory molecules may be engaged in reciprocal receptor-ligand downmodulation. Consistent with this, we observe that co-culture of CLL B cells with transfected murine plasmacytoma cells that express human CD70 affects downmodulation of CD27 and enhanced expression of CD70 on leukemic B cells, but does not affect expression of CD27 mRNA. However, we find that CD40-crosslinking, in addition to reducing the level of CD27 protein, also reduces leukemic B-cell expression of CD27 mRNA. This argues that the changes in the expression levels of CD27 following CD40-signaling are not simply due to induced increases in the expression levels of CD70. Finally, we demonstrate that reciprocal changes in expression of CD27 and CD70 may contribute to the enhanced antigen-presenting capacity of CLL B cells after CD40-dependent leukemic B-cell activation. These findings expand the understanding of the regulation of costimulatory molecules important in antigen presentation and also have implications for the immunobiology of and therapy for CLL.     

Clinical correlation of asbestos bodies in BAL fluid

BACKGROUND: Asbestos bodies (AB) in BAL cells are specific markers of asbestos exposure. METHODS: We retrospectively reviewed BAL cytocentrifuge slides of 30 utility workers with a history of asbestos exposure and 30 normal volunteers. BAL cytocentrifuge slides were blinded and scanned under 40 x light microscope. RESULTS: AB were found more frequently in subjects with a history of asbestos exposure compared to normal volunteers (10 of 30 subjects, 33%, vs 0 of 30 subjects). The mean number of AB seen in the AB-positive group was 2.7 per slide. Demographic data were comparable including age, gender, and smoking. Exposure histories were also similar: duration > 20 years, onset > 30 years ago, and time since last exposure > 7 years. More AB-positive patients reported respiratory symptoms (70% vs 26%, p < 0.05). High-resolution CT scans of AB-positive patients revealed a higher prevalence of parenchymal disease (70% vs 26%, p < 0.05). AB-positive subjects had reduced pulmonary function compared to AB-negative subjects: FVC (86% vs 97% predicted), FEV(1) (77% vs 92% predicted, p < 0.05), and diffusion capacity of the lung for carbon monoxide (76% vs 104% predicted, p < 0.01). CONCLUSION: In individuals with a history of asbestos exposure, the presence of AB in BAL cells is associated with higher prevalence of parenchymal abnormalities, respiratory symptoms, and reduced pulmonary function.     

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Assessment of Intestinal Permeability and Absorption in Cirrhotic Patients with Ascites Using Combined Sugar Probes

Gastrointestinal dysfunction in patients with cirrhosis may contribute to complications such as malnutrition and spontaneous bacterial peritonitis. To determine whether cirrhotic patients with ascites have altered intestinal function, we compared intestinal permeability and absorption in patients with liver disease and normal subjects. Intestinal permeability and absorption were investigated in 66 cirrhotic patients (48 with ascites, 18 without ascites) and 74 healthy control subjects. Timed recovery of 3-O-methyl-D-glucose, D-xylose, L-rhamnose, and lactulose in urine following oral administration was measured in order to assess active and passive carrier-mediated, and nonmediated, absorptive capacity, as well as intestinal large-pore/small-pore (lactulose/rhamnose) permeability. Test sugars were measured by quantitative thin-layer chromatography and results are expressed as a percentage of test dose recovered in a 5-h urine collection. Sugar excretion ratios relating to small intestinal permeability (lactulose/rhamnose) and absorption (rhamnose/3-O-methyl-D-glucose) were calculated to avoid the effects of nonmucosal factors such as renal clearance, portal hypertension, and ascites on the recovery of sugar probes in urine. Compared with normal subjects, the mean lactulose/rhamnose permeability ratio in cirrhotic patients with ascites was significantly higher (0.058 vs. 0.037, P < 0.001) but not in cirrhotic patients without ascites (0.041 vs. 0.037). Cirrhotic patients with ascites had significantly lower mean recoveries of 3-O-methyl-D-glucose (23.0 vs. 49.1%; P < 0.001), D-xylose (18.8 vs. 34.5%; P < 0.001), L-rhamnose (4.0 vs. 9.1%; P < 0.001), and lactulose (0.202 vs. 0.337%; P < 0.001) than normal subjects. However, the mean rhamnose/3-O-methyl-D-glucose ratio was the same in cirrhotic patients with ascites as normal subjects (0.189 vs. 0.189), indicating that the reduction in probe recovery was due to nonmucosal factors. Compared with normal subjects, cirrhotic patients with ascites have abnormal intestinal permeability, measured by urinary lactulose/rhamnose excretion, and normal small intestinal absorption, assessed by the urinary rhamnose/3-O-methyl-D-glucose ratio. Low urine recovery of sugar probes found in cirrhotic patients appears to be the result of nonintestinal factors affecting clearance rather than reduced intestinal absorption.     

Developing Signs of Safety: A Deaf-accessible counselling toolkit for trauma and addiction

The U.S. Deaf community—more than half a million Americans who communicate using American Sign Language (ASL)—experiences higher rates of trauma exposure and substance use disorder (SUD) than the general population. Yet there are no evidence-based treatments for any behavioural health condition that have been evaluated for use with Deaf people. The driving aim of our work, therefore, has been to develop and formally evaluate a Deaf-accessible trauma/SUD counselling approach. Here we describe our initial intervention development work and a single-arm pilot that evaluated the feasibility, acceptability, and preliminary clinical efficacy of Signs of Safety—a Deaf-accessible toolkit to be used with an existing, widely adopted protocol for trauma and addiction (Seeking Safety). Preliminary efficacy results indicated clinically significant reductions in PTSD symptoms and frequency of alcohol use for the Seeking Safety/Signs of Safety model. Frequency of drug use did not change significantly—likely attributable to the mid-study legalization of recreational marijuana in our state. Next steps include the redesign and refilming of Signs of Safety based on pilot participant feedback, again using a Deaf-engaged development and production process. This new toolkit will be tested via a pilot randomized controlled trial designed based on present methodological lessons learned.