Subjective work noise: A major risk factor in myocardial infarction

Summary The relationship between subjective work noise exposure and the risk of myocardial infarction (MI) was assessed in a population based casecontrol study. 395 MI patients (31–65 years) were compared to 2148 controls from a random population sample with the same age/sex distribution. The relative risk (RR) for MI—adjusted for control variables (smoking, age, social status, etc.)—was found to increase significantly and steadily with noise category. Subjective work noise exposure was the second greatest risk factor for MI after smoking. Possible bias due to overreporting of subjective noise exposure is discussed. Interdisciplinary studies on the relationship between cardiovascular diseases and workrelated stressors including subjective and objective noise assessment are needed to quantify the risk of MI due to work noise.

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Zusammenfassung In einer bevölkerungsbezogenen Fall-Kontroll-Studie wurde der Zusammenhang zwischen der subjektiven Arbeitslärmbelastung und dem Herzinfarktrisiko untersucht. 395 Herzinfarktpatienten im Alter von 31 bis 65 Jahren wurden mit 2148 Kontrollpersonen aus einer Zufallsstichprobe mit gleicher Alters- und Geschlechtsverteilung verglichen. Das relative Risiko für Herzinfarkt—adjustiert bezüglich mehrerer Einflussvariablen wie Rauchen, Alter, Sozialstatus usw.—stieg signifikant und monoton mit der Arbeitslärmbelastung an. Die subjektive Arbeitslärmbelastung erwies sich als der zweitwichtigste Risikofaktor für Herzinfarkt nach dem Rauchen. Mögliche Fehler wie z.B. Überbewertung der subjektiven Lärmbelastung werden diskutiert. Interdisziplinäre Studien zum Zusammenhang zwischen kardiovaskulären Erkrankungen und arbeitsplatzbezogenen Stressoren mit Erfassung der subjektiven und der objektiven Lärmbelastung sind notwendig, um das Herzinfarktrisiko durch Arbeitslärm zu quantifizieren.

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Résumé Le rapport entre la perception subjective de bruit gênant et le risque d'infarctus du myocarde (IM) fait l'objet d'une étude comparative portant sur 395 malades (IM) âgés de 31 à 65 ans et 2148 cas témoins sortis d'un sondage aléatoire parmi la population générale tout en assurant la même distribution d'âge et de sexe. II s'avère que—après la rectification exigée par les variables telles que consommation de tabac, âge, couche sociale, etc.—le risque relatif (RR) de IM augmente de manière significative et constante avec le gêne causé par le bruit au lieu de travail. Pour le IM, la perception subjective du bruit vécu au lieu de travail est le deuxième facteur de risque, son importance n'étant dépassée que par le tabagisme. Les auteurs discutent l'incidence possible d'une notification exagérée de bruit gênant. Afin de calculer le risque d' IM attributable au bruit perçu au lieu de travail, des études interdisciplinaires devraient être réalisées pour examiner les liens entre les maladies cardiovasculaires et les stresseurs liés au travail, y compris l'évaluation subjective et objective du bruit.

     

Intraluminal Radiation for Esophageal Cancer: A Howard University Technique

The objective of radiotherapeutic management in esophageal cancer is to accomplish maximum tumor sterilization with minimal normal tissue damage. This sincere effort is most often countered by the differential in tumor dose response vs normal tissue tolerance. Intraluminal isotope radiation, with its inherent advantage of rapid dose falloff, spares the lungs, the spinal cord, and other vital structures, yet yields adequately high doses to esophageal tumor. Though in existence since the turn of the century, the method of intracavitary radium bougie application dropped out of favor due to technical difficulties imposed by the size of the radium source and radiation exposure to the personnel involved. The authors describe a simple “iridium 192 afterloading intraluminal technique” that eliminates technical problems and reduces radiation exposure considerably.     

Leukocyte apoptosis and its significance in sepsis and shock

Sepsis and multiple organ failure continue to be significant problems among trauma, burn, and the critically ill patient population. Thus, a number of laboratories have focused on understanding the role of altered apoptotic cell death in contributing to immune and organ dysfunction seen in sepsis and shock. Immune cells that undergo altered apoptotic changes include neutrophils, macrophages, dendritic cells, as well as various lymphocyte populations. Evidence of epithelial as well as endothelial cell apoptotic changes has also been reported. Although mediators such as steroids, tumor necrosis factor, nitric oxide, C5a, and Fas ligand (FasL) appear to contribute to the apoptotic changes, their effects are tissue- and cell population-selective. As inhibiting Fas-FasL signaling (e.g., gene deficiency, Fas fusion protein, or Fas short interfering RNA administration), caspase inhibition (caspase mimetic peptides), and/or the overexpression of downstream antiapoptotic molecules (e.g., Bcl-2, Akt) improve survival of septic mice, it not only demonstrates the pathological significance of this process but points to novel targets for the treatment of sepsis.     

Values and ethics: a collection of curricular reforms for a new generation of physicians.

In recent years, medical educators have expressed concern that the reductionist-positivist mode of medical education fails to equip physicians with the skills and attitudes to meet the full range of patients' physical and emotional needs. Indeed, the authors suggest that neither patients nor physicians are satisfied. Among the factors responsible are a pervasive industrialization of clinical practice, a progressive segmentation of patient care, and a deepening shortage of both primary care and specialty physicians. But underlying these system issues is a lack of adequate schooling in the values, ethics, and culture of caring. Today's physicians must simultaneously be analytical, perceptive, and self-reflective. They must have the capacity to see their patients as individuals with differing psychological, social, and historical natures. And they must have insight into their own values and behaviors. All of this contributes to making a competent and humane physician. To aid medical students in achieving these characteristics, the authors contend that medical education must be radically restructured so that knowledge and skills are taught within the context of values and ethics. This commentary explores such reform through the lens of three articles published in the current issue of Academic Medicine, by Litzelman and Cottingham, Kanter and colleagues, and Dobie. These articles are the product of a national call that resulted in more than thirty abstracts, testimony to the fertile thinking already being applied to this problem. It is the authors' hope that this series of papers will stimulate still more thinking and lead to the curricular reform that future generations of physicians deserve.     

Proximal tubular epithelial cell integrins respond to high glucose by altered cell-matrix interactions and differentially regulate matrixin expression

Thickening of the tubular basement membrane (TBM) occurs in diabetic nephropathy, but the effects of high glucose on the functional aspects of proximal tubular epithelial cells are not clearly understood. In the present study, we examined the effects of elevated glucose concentrations on (a) integrin expression by human proximal tubular epithelial cells (HK-2) and integrin-mediated interactions with type IV collagen (colIV) and laminin, major components of TBM; (b) the expression of matrixins/matrix metalloproteinases (MMPs), which is regulated by integrins; and (c) the expression of tissue inhibitors of metalloproteinases (TIMPs). HK-2 cells cultured in 25 mM glucose underwent a reduction of the expression of alpha3, beta1, alpha(v)beta3, and alpha5 integrin subunits, with a concomitant increase of the alpha2 subunit, compared with cells grown in 5 mM glucose. Adhesion experiments demonstrated that high glucose led to increased cell adhesion on either colIV or laminin. Experiments of competition of adhesion using anti-integrin antibodies indicated that HK-2 cells in 5 mM glucose used mainly alpha(v)beta3 and alpha5beta1 integrins to adhere to colIV, whereas in 25 mM glucose they additionally used alpha2beta1. In the case of laminin, a beta1-mediated adhesion was observed when HK-2 cells were in 5 mM glucose, whereas in 25 mM glucose, alpha2beta1 and alpha(v)beta3 were also involved. Elevated glucose concentrations resulted in decreased expression of MMP-9 and MMP-2, whereas an increase in TIMP-1 and a decrease in TIMP-2 expression were observed. We also examined which integrins mediated the expression and secretion of matrixins MMP-2 and MMP-9. Ligation of alpha3beta1 with mAbs resulted in induction of MMP-2 expression and secretion, whereas antibody ligation of alpha(v)beta3 led to down-regulation of MMP-9. The above data implicate integrins of proximal tubular epithelial cells in the regulation of MMPs and in the development of TBM thickening in diabetic nephropathy.     

Immediate breast reconstruction-impact on radiation management

Breast reconstruction is an option for women undergoing modified radical mastectomy due to a diagnosis of breast cancer. In certain patients, breast reconstruction is performed by insertion of a temporary tissue expander prior to the placement of permanent breast implants. Some of these patients, following mastectomy, may require chest wall irradiation to prevent loco regional relapse. The compatibility of radiation and tissue expanders placed in the chest wall is of major concern to the radiation oncologist. Clinically undetectable changes can occur in the tissue expander during the course of radiation therapy. This can lead to radiation treatment set-up changes, variation in tissue expansion resulting in unwanted cosmesis, and deviation from the prescribed radiation dose leading to over and/or under dosing of tumor burden. At Howard University hospital, a CT scan was utilized to evaluate the status of the temporary tissue expander during radiation treatment to enable us to prevent radiation treatment related complications resulting from dosimetric discrepancies. CT images of the tissue expander were obtained through the course of treatment. To avoid a 'geographic miss' the amount of fluid injected into the tissue expander was kept constant following patient's satisfaction with the size of the breast mound. The CT scans allowed better visualization of the prosthesis and its relation to the surrounding tumor bed. This technique ensured that anatomical changes occurring during radiation treatment, if any, were minimized. Repeated dosimetry evaluations showed no changes to the prescribed dose distribution. A CT of the reconstructed breast provides an important quality control. Further studies with greater number of patients are required for confirming this impact on radiation treatment.     

Procedure for Fluorescent-Antibody Staining of Virus-Infected Cell Cultures in Plastic Plates

Acetone fixation and fluorescent-antibody staining of virus-infected cell cultures were performed in plastic plates. Proper addition of acetone as a fixative did not alter the plastic.     

Intraventricular insulin and leptin reverse place preference conditioned with high-fat diet in rats

The authors hypothesized that insulin and leptin, hormones that convey metabolic and energy balance status to the central nervous system (CNS), decrease the reward value of food, as assessed by conditioned place preference (CPP). CPP to high-fat diet was blocked in ad-lib fed rats given intraventricular insulin or leptin throughout training and test or acutely before the test. Insulin or leptin given only during the training period did not block CPP. Thus, elevated insulin and leptin do not prevent learning a food's reward value, but instead block its retrieval. Food-restricted rats receiving cerebrospinal fluid, insulin, or leptin had comparable CPPs. Results indicate that the CNS roles of insulin and leptin may include processes involving memory and reward.     

Functional expression and properties of the human skeletal muscle sodium channel

Full-length deoxyribonucleic acid, complementary (cDNA) constructs encoding the-subunit of the adult human skeletal muscle Na⁺ channel, hSkM1, were prepared. Functional expression was studied by electrophysiological recordings from cRNA-injectedXenopus oocytes and from transiently transfected tsA201 cells. The Na⁺ currents of hSkM1 had abnormally slow inactivation kinetics in oocytes, but relatively normal kinetics when expressed in the mammalian cell line. The inactivation kinetics of Na⁺ currents in oocytes, during a depolarization, were fitted by a weighted sum of two decaying exponentials. The time constant of the fast component was comparable to that of the single component observed in mammalian cells. The block of hSkM1 Na⁺ currents by the extracellular toxins tetrodotoxin (TTX) and -conotoxin (CTX) was measured. The IC₅₀ values were 25 nM (TTX) and 1.2 M (CTX) in oocytes. The potency of TTX is similar to that observed for the rat homolog rSkM1, but the potency of CTX is 22-fold lower in hSkM1, primarily due to a higher rate of toxin dissociation in hSkM1. Single-channel recordings were obtained from outside-out patches of oocytes expressing hSkM1. The single-channel conductance, 24.9 pS, is similar to that observed for rSkM1 expressed in oocytes.