Risk of injury: a case-crossover analysis of injured emergency service patients in poland

BACKGROUND: Over the last 15 years large changes in both alcohol consumption and the health care system have occurred in Poland. Substantial fluctuations in alcohol-related mortality followed and burden on health services increased, but data on risk of injury from alcohol consumption are relatively scarce METHODS: Estimates for risk of injury from drinking within six hours prior to the event are reported in samples of emergency services patients from Warsaw (n=508) and Sosnowiec (n=432), using case-crossover analysis based on usual frequency of drinking RESULTS: A four-fold risk of injury was found for those reporting drinking prior to injury compared to those not drinking, and this was significantly greater for those positive for alcohol use disorders compared to those negative. Relative risk of injury was marginally greater in Sosnowiec (5.2) compared to Warsaw (3.4) (p=0.06), and was significantly greater for those under 30. A 17-fold increase in risk for violence-related injury was found, and was significantly greater for females than males. Risk was substantially greater in Sosnowiec compared to Warsaw across all subgroups, but differences were not significant, possibly due to the small numbers of those sustaining injuries from violence in Warsaw. DISCUSSION: Injury risk related to drinking was expected to be significantly greater in Sosnowiec, due to more traditional drinking styles of infrequent intake of large quantities of spirits, than in Warsaw, but this was only partially borne out by these data. Risk estimates for all injuries were similar to those found in other case-crossover studies in emergency departments. Given the high relative risk estimates for injury related to drinking prior to the event, among both problem and non-problem drinkers, hospital-based emergency services in Poland may be an important site for identification of those who could benefit from a brief intervention or referral for a reduction in alcohol-related injuries.     

Emotional distress in chronic hepatitis C patients not receiving antiviral therapy

BACKGROUND/AIMS: The aim of our study was to determine the prevalence, type, and severity of emotional distress in a large group of consecutive chronic hepatitis C (CHC) patients not receiving anti-viral therapy. METHODS: The brief symptom inventory and a 67-item questionnaire with the SF-36 embedded within it were used to study 220 outpatients with compensated CHC. RESULTS: Seventy-seven (35%) participants reported significantly elevated global severity index (GSI) T-scores compared to an expected frequency of 10% in population controls. In addition, significantly elevated depression, anxiety, somatization, psychoticism, and obsessive-compulsive subscale T-scores were reported in 28-40% of subjects. Subjects with an active psychiatric co-morbidity had significantly higher GSI and subscale T-scores compared to subjects with active medical co-morbidities and subjects without medical or psychiatric co-morbidities (P<0.01). However, patients with CHC alone also had a higher frequency of elevated GSI T-scores compared to population controls (20 versus 10%). GSI and subscale T-scores were strongly associated with SF-36 summary scores (P<0.001). CONCLUSIONS: Clinically significant emotional distress was reported in 35% of CHC patients not receiving antiviral therapy. In addition to depression, a broad array of psychological symptoms were observed. Further investigation into the etiopathogenesis and treatment of emotional distress in CHC patients is warranted.     

Isolation and localization of DNA segments from specific human chromosomes

Recombinant DNA techniques have been combined with somatic cell genetic methods to identify, isolate, and amplify fragments of human DNA localized at specific regions of human chromosome 11 selected as a model system. A library of genomic DNA segments has been constructed, in λ Charon 4A bacteriophage, from the DNA of a somatic cell hybrid carrying a portion of human chromosome 11 on a Chinese hamster ovary cell background. Using a nucleic acid hybridization technique that distinguishes human and Chinese hamster interspersed, repetitive DNA, we have been able to distinguish recombinant phages carrying DNA segments of human origin from recombinant phages carrying DNA segments of Chinese hamster origin. We have isolated 50 human DNA segments thus far and have characterized 5 in detail. For each DNA segment characterized, a subsegment that carries no repetitive human DNA sequences has been identified. These segments have been used as hybridization probes in experiments that localize the DNA fragment on the chromosome. In each case an unequivocal chromosomal localization has been obtained with reference to a panel of hybrid cell clones each of which carries a deletion of a portion of the short arm of chromosome 11. At least one DNA segment has been identified which maps to each of the four regions on the short arm defined by the panel of hybrid cell clones used. The approaches described here appear to be general. They can be extended to produce a fine structure map of human chromosome 11 and other human chromosomes. This approach promises implications for human genetics generally, for the human genetic diseases, and possibly for understanding of gene regulation in normal and abnormal differentiation.     

The role of ubiquitous airborne fungi in chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a confusing disease for both allergists and otorhinolaryngologists, partially due to its poorly understood pathophysiology and partially due to its limited treatment options. Several recent reports now provide evidence for a better understanding of the etiology and the relationship of CRS to airborne fungi, especially to Alternaria. First, the development of novel methods enables detection of certain fungi in mucus from the nasal and paranasal sinus cavities. Second, a non-immunoglobulin E-mediated immunologic mechanism for reactivity of CRS patients to certain common fungi has been described. Third, these fungi are surrounded by eosinophils in vivo, suggesting that they are targeted by eosinophils. Fourth, the preliminary results of studies using antifungal agents to treat patients with CRS are promising. Overall, these recent discoveries provide a logical mechanism for the pathophysiology of CRS, and they also suggest promising avenues for treatment of CRS with antifungal agents.     

Electrocardiogram abnormalities predict angiographic coronary artery disease in women with chest pain: results from the NHLBI WISE Study

BACKGROUND AND HYPOTHESIS: Noninvasive risk stratification for coronary artery disease (CAD) isless accurate in women than in men. Based on recent reports that gender-specific exercise electrocardiogram (ECG) parameters predict CAD, we evaluated the independent predictive value of the resting ECG for angiographic CAD in women with chest pain. METHODS: Women (n = 850, mean age 58 years) with chest pain in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) underwent 12-lead ECG testing and quantitative coronary angiography. RESULTS: Significant angiographic CAD (> or = 50% stenosis in > or = 1 coronary) was present in 39% of women. Q waves in < or = 2 contiguous ECG leads were present in 107 women (13%), including 49 of 657 (7%) without history of infarction. Among 585 women without prior infarction orrevascularization, 48% of those with Q waves in contiguous leads versus 26% of others, had significant CAD (p = 0.003; odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.3-4.8). Women with Q waves in < or = 2 inferior ECG leads were particularly likely to have CAD (63 vs. 26% of others, p < 0.001; OR = 4.6,95% CI = 2.0-10.8). Other ECG findings predictive of CAD were any ST-T abnormality (OR = 1.9,95% CI = 1.3-2.8) and T-wave inversion (OR = 2.4, 95% CI = 1.3-4.2). In risk-adjusted analysis, inferior Q waves and T-wave inversion independently predicted significant CAD. When considered together with radionuclide perfusion test results, T-wave inversion on resting ECG added significant independent predictive value (OR = 2.8, 95% CI = 1.1-7.2, p = 0.03). CONCLUSIONS: Selected resting ECG parameters independently predict angiographic CAD in women with chest pain, including women who have also undergone radionuclide stress testing. Prospective studies should consider resting ECG parameters in diagnostic algorithms for CAD in women.     

Mutations in herpes simplex virus glycoprotein D that prevent cell entry via nectins and alter cell tropism

Glycoprotein D (gD) determines which cells can be infected by herpes simplex virus (HSV) by binding to one of the several cell surface receptors that can mediate HSV entry or cell fusion. These receptors include the herpesvirus entry mediator (HVEM), nectin-1, nectin-2, and sites in heparan sulfate generated by specific 3-O-sulfotransferases. The objective of the present study was to identify residues in gD that are critical for physical and functional interactions with nectin-1 and nectin-2. We found that double or triple amino acid substitutions at positions 215, 222, and 223 in gD caused marked reduction in gD binding to nectin-1 and a corresponding inability to function in cell fusion or entry of HSV via nectin-1 or nectin-2. These substitutions either enhanced or did not significantly inhibit functional interactions with HVEM and modified heparan sulfate. These and other results demonstrate that different domains of gD, with some overlap, are critical for functional interactions with each class of entry receptor. Viral entry assays, using gD mutants described here and previously, revealed that nectins are the principal entry receptors for selected human cell lines of neuronal and epithelial origin, whereas HVEM or nectins could be used to mediate entry into a T lymphocyte line. Because T cells and fibroblasts can be infected via HVEM, HSV strains carrying gD mutations that prevent entry via nectins may establish transient infections in humans, but perhaps not latent infections of neurons, and are therefore candidates for development of safe live virus vaccines and vaccine vectors.     

Tissue-Specific Cytokine Production During Experimental Acute Pancreatitis (A Probable Mechanism for Distant Organ Dysfunction)

Our purpose was to determine if cytokines are produced systemically during acute pancreatitis. Proinflammatory cytokines are elevated during acute pancreatitis and have been implicated in the progression of pancreatitis-associated multiple organ dysfunction. Whether these mediators are produced within all tissues or very few specific organs is not known. Edematous pancreatitis was induced in adult male mice by IP injection of cerulein. Necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented diet.Animals were sacrificed as pancreatitis worsened, with multiple organs prepared for tissue mRNA and protein analysis by RT-PCR and immunoblotting.Pancreatitis severity was established by histologic grading and serum amylase and lipase. There was no cytokine mRNA or protein detectable prior to the induction of pancreatitis. Tumor necrosis factor- (TNF-) and interleukin-1- (IL-1) mRNA and protein were detected within the pancreas early in the course of pancreatitis in both models,coinciding with the development of hyperamylasemia (both P < 0.001). Interleukin-6 was produced in the pancreas after pancreatitis was more fully developed (P< 0.001). IL-1 and TNF- were subsequently produced in large amounts in lung, liver, and spleen but never within kidney, cardiac muscle, or skeletal muscle.A significant delay between pancreatic and distant organ cytokine production was always observed.It is concluded that proinflammatory cytokines are produced within the pancreas and within organs known to develop dysfunction during severe pancreatitis. Cytokine production is tissue specific,correlates with disease severity, and occurs within the pancreas first and subsequently within distant organs.