C-reactive protein, interleukin-6, secretory phospholipase A2 group IIA and intercellular adhesion molecule-1 in the prediction of late outcome events after acute coronary syndromes

OBJECTIVE: We investigated whether levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A(2) group IIA (sPLA(2)-IIA) and intercellular adhesion molecule-1 (ICAM-I) predict late outcomes in patients with acute coronary syndromes (ACS). DESIGN: Prospective longitudinal study. CRP (mg L(-1)), IL-6 (pg mL(-1)), sPLA(2)-IIA (ng mL(-1)) and ICAM-1 (ng mL(-1)) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS. Their relations to mortality and rehospitalization for myocardial infarction (MI) and congestive heart failure (CHF) were determined. SETTING: Coronary Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Patients with ACS alive at day 30; median follow-up 75 months. RESULTS: Survival was related to day 1 levels of all markers. After adjustment for confounders, CRP, IL-6 and ICAM-1, but not sPLA(2)-IIA, independently predicted mortality and rehospitalization for CHF. For CRP, the hazard ratio (HR) was 1.3 for mortality (95% confidence interval (CI): 1.1-1.5, P = 0.003) and 1.4 for CHF (95% CI: 1.1-1.9, P = 0.006). For IL-6, HR was 1.3 for mortality (95% CI: 1.1-1.6, P < 0.001) and 1.4 for CHF (95% CI: 1.1-1.8, P = 0.02). For ICAM-1, HR was 1.2 for mortality (95% CI: 1.0-1.4, P = 0.04) and 1.3 for CHF (95% CI: 1.0-1.7, P = 0.03). No marker predicted MI. Marker levels on day 4 provided no additional predictive value. CONCLUSIONS: In patients with ACS, CRP, IL-6, sPLA(2)-IIA and ICAM-1 are associated with long-term mortality and CHF, but not reinfarction. CRP, IL-6 and ICAM-1 provide prognostic information beyond that obtained by clinical variables.     

Prevalence of the inactivating 609C-->T polymorphism in the NAD(P)H:quinone oxidoreductase (NQO1) gene in patients with primary and therapy-related myeloid leukemia.

NAD(P)H:quinone oxidoreductase (NQO1) converts benzene-derived quinones to less toxic hydroquinones and has been implicated in benzene-associated hematotoxicity. A point mutation in codon 187 (Pro to Ser) results in complete loss of enzyme activity in homozygous subjects, whereas those with 2 wild-type alleles have normal activity. The frequency of homozygosity for the mutant allele among Caucasians and African Americans is 4% to 5% but is higher in Hispanics and Asians. Using an unambiguous polymerase chain reaction (PCR) method, we assayed nonmalignant lymphoblastoid cell lines derived from 104 patients with myeloid leukemias; 56 had therapy-related acute myeloid leukemia (t-AML), 30 had a primary myelodysplastic syndrome (MDS), 9 had AML de novo, and 9 had chronic myelogenous leukemia (CML). All patients had their leukemia cells karyotyped. Eleven percent of the t-AML patients were homozygous and 41% were heterozygous for the NQO1 polymorphism; these proportions were significantly higher than those expected in a population of the same ethnic mix (P =.036). Of the 45 leukemia patients who had clonal abnormalities of chromosomes 5 and/or 7, 7 (16%) were homozygous for the inactivating polymorphism, 17 (38%) were heterozygous, and 21 (47%) had 2 wild-type alleles for NQO1. Thus, NQO1 mutations were significantly increased compared with the expected proportions: 5%, 34%, and 61%, respectively (P =.002). An abnormal chromosome no. 5 or 7 was observed in 7 of 8 (88%) homozygotes, 17 of 45 (38%) heterozygotes, and 21 of 51 (41%) patients with 2 wild-type alleles. Among 33 patients with balanced translocations [14 involving bands 11q23 or 21q22, 10 with inv(16) or t(15;17), and 9 with t(9;22)], there were no homozygotes, 15 (45%) heterozygotes, and 18 (55%) with 2 wild-type alleles. Whereas fewer than 3 homozygotes were expected among the 56 t-AML patients, 6 were observed; 19 heterozygotes were expected, but 23 were observed. The gene frequency for the inactivating polymorphism (0. 31) was increased approximately 1.4-fold among the 56 t-AML patients. This increase was observed within each of the following overlapping cohorts of t-AML patients: the 43 who had received an alkylating agent, the 27 who had received a topoisomerase II inhibitor, and the 37 who had received any radiotherapy. Thus, the frequency of an inactivating polymorphism in NQO1 appears to be increased in this cohort of myeloid leukemias, especially among those with t-AML or an abnormality of chromosomes 5 and/or 7. Homozygotes and heterozygotes (who are at risk for treatment-induced mutation or loss of the remaining wild-type allele in their hematopoietic stem cells) may be particularly vulnerable to leukemogenic changes induced by carcinogens.     

Effects of inhaled corticosteroid on bone turnover in children with bronchial asthma

Long-term usage of systemic steroids is associated with multiple side effects. One of the major morbidities is due to its effect on bone metabolism leading to bone loss and resulting in skeletal fractures. This study was conducted to determine the effects of inhaled steroids on bone mineral density (BMD) and biochemical bone markers. Twenty-four children with frequent episodic or mild persistent asthma who satisfied the clinical criteria for starting on inhaled corticosteroids (ICS) were enrolled into the study. The BMD scan was done using dual energy X-ray absorptiometry, prior to starting ICS therapy and 6 months later. Biochemical markers of bone metabolism, (i) serum osteocalcin as a bone formation marker, and (ii) urinary deoxypyridinoline (Upd) as a bone resorption marker, were taken prior to ICS treatment and at 2 monthly intervals. The biochemical markers were all taken in the morning. Twenty-four, age- and sex-matched children with mild episodic asthma, not requiring ICS, were used as controls for the BMD measurements. The BMD scan was done upon enrollment into the study and 6 months later. Twenty-four children on ICS and 24 controls completed the study. The subjects were on a mean dose of beclomethasone dipropionate (BDP) 0.4 mg/day. One subject needed a short course of Prednisolone in the early treatment period. None of the controls needed oral steroid therapy. One child in the control group sustained a greenstick fracture after an accidental fall. The mean rate of change of BMD was 1.8% +/- 12.3 in the subjects on BDP. This was lower than the 6.1% +/- 10.6 among the control subjects. However, this difference did not reach statistical significance (P = 0.16). There was a significant increase in serum osteocalcin level after 6 months of BDP treatment from 66.83 +/- 22.71 ng/mL to 81.61 +/- 24.66 ng/mL (P < 0.005). There was a decline in Upd from 36.2 +/- 47.1 nmol/mmol creatinine to 21.4 +/- 6.92 nmol/mmol creatinine. However, this did not reach statistical significance. There was no difference in the statural gain between the subjects on ICS and their controls. This study showed that 6 months of ICS therapy (mean dose 0.4 mg/day) had no significant adverse effect on bone metabolism in asthmatic children.     

Randomized controlled trial of a telephone intervention by nurses to provide information and support to patients and their partners after elective coronary artery bypass graft surgery: effects of anxiety

OBJECTIVE: The purpose of this study was to determine the effectiveness of an information and support telephone intervention for reducing anxiety in patients who have undergone coronary artery bypass graft surgery and their partners. DESIGN: The study is a randomized controlled trial. Intervention began at discharge; 6 telephone calls were made to patients and partners over 7 weeks. Primary outcome was Beck Anxiety Inventory measured at baseline in hospital, at home on day 3, week 4, and week 8. SAMPLE: The subjects were 131 patients who have undergone elective coronary artery bypass graft surgery and their partners. RESULTS: Patients' anxiety was moderate to severe the day before discharge. It was significantly lower in the treatment group than in the control group at day 2 at home. Partners always had lower anxiety than patients. A more sustained decrease in anxiety in the partner treatment group was found at both day 2 and week 4. CONCLUSION: Intervention effect is in the early period after discharge-- the time most affected by reduced lengths of stay.     

Estimating the population at risk for Ontario Workplace Safety and Insurance Board-covered injuries or diseases

Difficulty in quantifying the population at risk for a work-related injury or disease limits the usefulness of workers' compensation data for surveillance. This article presents a method of obtaining estimates of the Ontario Workplace Safety and Insurance Board (OWSIB)- covered workforce using the Canadian Labour Force Survey (LFS). The method involves extracting that class of worker most likely to be insured by the OWSIB and using actual hours worked to estimate full-time equivalents at risk. Compared to population at risk estimates readily available from published tables, the refined crude estimate was 26% lower and ranged from 15 to 79% lower depending on the age group. The percentage decrease from published estimates was generally greater for women compared to men, particularly in the 25 to 39 year age categories. Consequently, the method of deriving population at risk estimates should be considered when comparing rates across sexes, ages, industries or occupations.     

Work-related cumulative trauma disorders of the upper extremity: navigating the epidemiologic literature

BACKGROUND: Cumulative trauma disorder of the upper extremity (CTDUE) is an umbrella term used to describe disorders resulting from repeated use of the upper extremity over time rather than a specific incident. The primary purpose of this article is to summarize the literature regarding the rate of work-related CTDUE, while drawing attention to the various factors contributing to the wide range of reported findings. METHODS: The Cumulative Index to Nursing and Allied Health and Medline databases were searched for articles focusing on etiology or rates of occurrence of work-related CTDUE and their findings were summarized. RESULTS: Potential reasons for rising rates, a gender differential, and the substantial range in rates and rate ratios are delineated and important factors to consider when interpreting rates derived from workers' compensation data are detailed. CONCLUSIONS: Future research should attempt to correctly identify more specific categories of CTDUE in well-defined and accurately-quantified "at risk" populations to provide more meaningful information regarding the epidemiology of CTDUE and the effectiveness of control activities.     

Zyxin and vinculin distribution at the Cell‐extracellular Matrix Attachment Complex (CMAX) in corneal epithelial tissue are actin dependent

Avian embryonic corneal epithelia are two cell layers thick. If isolated without (−) basal lamina, the basal cells have unorganized actin and project cytoplasmic protrusions termed blebs. The actin‐based cytoskeleton at the cell‐extracellular matrix junction (termed the actin cortical mat) is disrupted. These epithelia respond to soluble extracellular matrix molecules by reorganizing the actin cortical mat. Sheets of epithelia were isolated + or ‐basal lamina. Epithelia isolated ‐basal lamina were cultured ± laminin‐1 and/or ± cytochalasin D (CD). The intracellular localization of zyxin, vinculin, paxillin, focal adhesion kinase, and tensin was determined using indirect immunohistochemistry. Protein levels were determined by Western blot analysis. Zyxin and vinculin were concentrated in two areas of the tissue. The interface between the upper cell layer (periderm) and the basal cells. The second area of concentration was at the inferior 1–4 microns of the basal cells in an area with multiple actin bundles termed the actin cortical mat. The actin bundles align toward zyxin and vinculin that were located near basal lateral membranes. Zyxin was displaced from the basal compartment of blebbing basal cells. In contrast tensin, vinculin and focal adhesion kinase were found diffusely throughout the blebs. Zyxin and vinculin redistributed to the basal‐lateral membranes as actin bundles reorganized in laminin‐stimulated epithelia. In contrast to the altered protein distribution, extractable protein levels were similar in blebbing and laminin‐stimulated epithelia. Zyxin, vinculin, and other associated proteins were disrupted in the CD‐treated tissues and do not colocalize with each other or CD‐induced actin aggregates. The intracellular localization of zyxin and vinculin were concentrated in distinct areas along the inferior basolateral membranes of basal cells termed the cell‐extracellular matrix attachment complex (CMAX). The distribution of CMAX proteins was dependent upon actin bundle organization. Anat Rec 254:336–347, 1999. © 1999 Wiley‐Liss, Inc.     

Is there a gender difference in aetiology of chest pain and symptoms associated with acute myocardial infarction?

Many previous studies have shown that there is a gender difference in terms of the use of diagnostic procedures and the treatment of patients with chest pain. The mechanisms behind these observations are less well described. This survey describes gender differences in the aetiology of chest pain and symptoms associated with acute myocardial infarction (AMI). Among the patients with symptoms of acute chest pain, in the emergency medical department women less frequently develop an AMI and are less frequently given a diagnosis of ischaemic heart disease. Among patients developing an AMI, women differ from men by less frequently reporting chest pain, more frequently reporting nausea, vomiting, abdominal complaints, fatigue and dyspnoea and less frequently reporting sweating. With regard to the localization of pain in AMI, women differ from men by more frequently reporting pain in the back, neck and jaw. In terms of electrocardiographic changes, women seem to have less marked ST deviations than men. However, we do not believe that these differences between women and men are substantial enough and, as a result, we do not recommend that the initial medical care of patients seeking medical attention with chest pain or other symptoms raising a suspicion of AMI should be differentiated with regard to gender. The differences described here might partly explain the prolonged delay until hospital admission in women suffering from AMI.