Asthma deaths during sports: report of a 7-year experience

BACKGROUND: Asthma mortality and the mortality of athletes during sports have been described separately in detail in the medical literature. However, asthma has not been reported as a cause of death in competitive athletes. OBJECTIVE: The object of this study was to raise the awareness of physicians, coaches, trainers, and parents that children and adults can have fatal asthma exacerbations during and immediately after participating in sports. METHODS: The Temple Sports Asthma Research Center identified athletes from 1993 until 2000 who died during or after sporting activity by using the nationwide Burrell's Information Service. Once a possible asthma-related sports death was identified, the autopsy report was requested from the coroner or medical examiner, and an attempt was made to contact the family. Contact with the family was limited to information about the death, medical history, sports involvement, and any medication usage by the person who had died. Secondary sources, including news reports, were used to confirm whether the subject died of asthma during or immediately after a sporting activity. RESULTS: Two hundred sixty-three possible cases were identified. Sixty-one deaths met the criteria for study inclusion. White deaths outnumbered black deaths by 2 to 1. Deaths among male subjects predominated. Most subjects were younger than the age of 20 years, with the most prevalent age group being between 10 to 14 years old. Fifty-one percent (18 of 35) of the competitive athletes had their fatal event while participating in organized sport, 14 in a practice situation and 4 deaths during a game or meet setting. Basketball and track were the 2 most frequent activities performed at the time of the fatal event. CONCLUSION: The subjects who had fatal asthma exacerbations were usually white male subjects between the ages of 10 and 20 years. Mild intermittent or persistent asthma by history was commonly identified. Sudden fatal asthma exacerbations occur in both competitive and recreational athletes and can be precipitated by sporting activity.     

Effects of estrogen replacement on the progression of coronary-artery atherosclerosis

BACKGROUND: Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. METHODS: We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography. RESULTS: Estrogen and estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however, neither treatment altered the progression of coronary atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02 mm, and 1.87+/-0.02 mm in women assigned to estrogen, estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences between the values for the two active-treatment groups and the value for the placebo group were not significant. Analyses of several secondary angiographic outcomes and subgroups of women produced similar results. The rates of clinical cardiovascular events were also similar among the treatment groups. CONCLUSIONS: Neither estrogen alone nor estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease. These results suggest that such women should not use estrogen replacement with an expectation of cardiovascular benefit.     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Differential regulation of transendothelial migration of THP-1 cells by ICAM-1/LFA-1 and VCAM-1/VLA-4

The adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressed in atherogenic lesions are thought to regulate monocyte diapedesis. To better understand their specific roles we used function-blocking antibodies and examined in a culture model the morphology, motility, and diapedesis of THP-1 cells interacting with human coronary artery endothelial cells. The number of motile THP-1 cells was reduced only when VCAM-1 or both ICAM-1 and VCAM-1 were blocked. Blockade of ICAM-1 and VCAM-1, either separately or together, reduced to the same degree the distance that THP-1 cells traveled. Diapedesis was reduced only during the simultaneous blockade of both adhesion molecules. Blockade of either ICAM-1 or VCAM-1 inhibited pseudopodia formation, but ICAM-1 blockade induced the formation of filopodia. We suggest that the interactions of endothelial ICAM-1 and VCAM-1 with their ligands differentially regulate distinct steps of diapedesis by modulating the ratio of active and inactive forms of small GTPases such as Rho, Rac, and Cdc42.     

Inhibition of chemotaxis of neutrophil leukocytes to interleukin-8 by endotoxins of various bacteria.

The effects of endotoxins from various bacteria (Escherichia coli, Klebsiella pneumoniae, Vibrio cholerae, Shigella flexneri, Salmonella typhosa, and Pseudomonas aeruginosa) on chemotaxis of neutrophil leukocytes to formyl peptide and interleukin-8 were tested in an improved chemotaxis assay involving a "sparse-pore" polycarbonate (Nuclepore) membrane in a Boyden-type chamber. The possible chemotactic activity of the endotoxins themselves were tested by the same technique. In addition, the effects of these substances on random motility of neutrophils were tested with a corresponding assay involving similar chambers fitted with membranes of standard pore density. Possible activation of the complement system of serum by each endotoxin was tested with sheep erythrocyte assays and the maximum endotoxin concentration (100 micrograms/ml) used in the chemotaxis and motility assays. All endotoxins inhibited chemotaxis of neutrophils to interleukin-8. No endotoxin affected chemotaxis to formyl peptide or was itself chemotactic for neutrophils. Endotoxin of S. flexneri inhibited random motility of neutrophils, while the others had no such effect. Endotoxins of K. pneumoniae and of P. aeruginosa produced moderate and marked inhibition, respectively, of total complement, as measured by hemolysis of sheep erythrocytes, without affecting the levels of C3c and C4 in these assays. Endotoxins of the other bacteria had no demonstrable effect in any of these assays of complement activation. These results suggest that chemotaxis to interleukin-8 may be mediated by cellular mechanisms different from those involved in chemotaxis to formyl peptide. Furthermore, the presence of these endotoxins could be significant for the suppression of neutrophil accumulation in inflammatory lesions mediated by interleukin-8.     

Strain variation among Bordetella pertussis isolates from Québec and Alberta provinces of Canada from 1985 to 1994

Pulsed-field gel electrophoresis and gene typing were able to differentiate among 3,597 Bordetella pertussis isolates circulating in Alberta and Québec Provinces, Canada, from 1985 to 1994 and distinguish them from the strains used in vaccine production. This study provides a baseline for continued surveillance of prevalent and emerging strains of B. pertussis in Canada.     

Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality

BACKGROUND: The follicular microenvironment is an important determinant of oocyte development. The aim of this study was to examine whether the myo-inositol (MI) content in human follicular fluid (FF) was associated with better oocyte quality. METHODS: A total of 53 patients treated with IVF was recruited to a prospective observational study. FF and serum samples collected were divided into two groups: group A consisted of FF associated with matured and fertilized oocytes, whilst group B was from follicles with immature and unfertilized oocytes. RESULTS: Patient's age, total ampoules of HMG used, days of stimulation, basal levels of FSH, estradiol (E(2)) levels on the day of HCG, and serum MI content were not significantly different between the two groups. FF volume and its MI content were significantly higher in group A compared with group B (P < 0.05). The levels of MI in FF were positively correlated with the amount of E(2) in their corresponding FF samples and also correlated with embryo quality. CONCLUSIONS: We propose that higher concentrations of MI and E(2) in human FF appear to play a role in follicular maturity and provide a marker of good quality oocytes.     

The clinical features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by arginine in the pro alpha 1(I) chain of type I procollagen.

The features of three babies with lethal perinatal osteogenesis imperfecta resulting from the substitution of glycine by arginine in the pro alpha 1(I) chain of type I procollagen were studied. The babies were heterozygous for this substitution at residue 391 in case 1 (0I24), 667 in case 2 (0I51), and 976 in case 3 (0I30). They were all small, term babies who died soon after birth. The ribs were broad and continuously beaded in 0I24, discontinuously beaded in 0I51, and slender with few fractures in 0I30. The overall radiographical classifications were type IIA in 0I24, IIA/IIB in 0I51, and IIB in 0I30. Histological examination confirmed that the long bones were misshapen and porotic. The calcified cartilage trabeculae were covered with an abnormally thin layer of osteoid and the bone trabeculae were thin and basophilic. There was no evidence of lamellar bone or Haversian systems. The osteoblasts remained relatively large and closely spaced. These babies shared many phenotypic features, but differences in the radiographical appearance of the ribs and long bones suggested that there was a gradient of bone modelling capacity from the slender and overmodelled bones in 0I30 to the absence of modelling in 0I24.     

Housing satisfaction for persons with psychiatric disabilities

Provision of residential services to people with mental illness has assumed increasing importance since deinstitutionalization and as community‐ based services have increased. This large‐scale multisite study of housing programs specifically for persons with mental illness examines one of the factors that lead to successful residential tenure for persons with serious mental illness. To date, the Lehman Quality of Life Scale has been used primarily to assess satisfaction with housing in studies of residential services. This article reports on a new measure of housing satisfaction. This new 25‐item instrument was developed, field tested in a variety of housing settings across the country, and analyzed for reliability and validity by a group of housing researchers and clinicians. The implications of using this instrument for future evaluation and research on housing for persons with mental illness are examined. © 2003 Wiley Periodicals, Inc. J Comm Psychol 31: 581–590, 2003.     

Plasmodium falciparum sexual stage antigens: immunogenicity and cell-mediated responses.

Antibody and cell-mediated immune responses to the transmission-blocking target antigens of Plasmodium falciparum, Pfs 48/45, were determined in infected non-immune patients and in immune individuals from an endemic area. Characterization of the B cell epitopes with monoclonal antibodies showed that there were five regions identifiable but there could be interactions between them causing either competitive or enhancing effects. Sera from infected non-immune patients contained antibodies that would compete with one or more of the mAbs to the different epitopes. Immune responsiveness to purified Pfs 48/45 in P. falciparum-immune adults measured as lymphoproliferation, production of interferon-gamma, or as Pfs 48/45-specific antibody was very limited. This did not appear to be due to MHC class II restriction, to diversity in structure of the parasite antigens or to a failure of immunological memory. The antibody-response data were more consistent with down-regulation of immunity as a result of prolonged exposure to infection.