The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction

P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable angina. We investigated the P-selectin gene as a possible candidate for myocardial infarction (MI). The P-selectin gene is situated on chromosome 1q21-q24, spans >50 kb and contains 17 exons. The sequences of the 5'-flanking region and exons of 40 alleles from patients with MI were screened for polymorphisms using polymerase chain reaction/single-strand conformation polymorphism (PCR-SSCP) and sequencing. Thirteen polymorphisms were identified: five in the 5'-flanking and eight in the exonic sequences. Four polymorphisms (Ser290Asn, Asn562Asp, Leu599Val and Thr715Pro) predicted a change in the amino acid sequence of the P- selectin protein. All P-selectin polymorphisms as well as a common E- selectin polymorphism, Ser128Arg which has been reported as being associated with an increased risk of premature coronary heart disease (CHD), and is in tight linkage disequilibrium with several P-selectin polymorphisms, were investigated in 647 patients with MI and 758 control subjects from four regions of France and Northern Ireland (the ECTIM study). The entire set of P-selectin polymorphisms provided a heterozygosity of 91%. The polymorphisms were tightly associated with one another and displayed patterns of linkage disequilibrium suggesting the existence of highly conserved ancestral haplotypes. The five polymorphisms in the 5'-flanking region of the gene were unrelated to MI or any relevant phenotype measured in the ECTIM study. We inferred that the four missense variants identified in the coding region predicted eight common forms of the P-selectin protein. The Pro715 allele which characterizes one of these forms was less frequent in France than in Northern Ireland ( P < 0.002) and in cases than in controls ( P < 0.002; P < 0.02 after correction for the number of tests). We conclude that the P-selectin gene is highly polymorphic and hypothesize that the Pro715 variant may be protective for MI. Whether this variant affects the properties of the P-selectin protein in a way which is compatible with this hypothesis needs to be checked experimentally.      

Sperm quality in Hodgkin's disease versus non-Hodgkin's lymphoma

The study was conducted to determine the deleterious effect of lymphoma disease on spermatogenesis and to evaluate the possibility that the disease is mediated primarily by inherent mechanisms in Hodgkin's disease and non-Hodgkin's lymphoma patients. A total of 89 patients with lymphoma disease (Hodgkin's and non-Hodgkin's) were referred for sperm preservation prior to adjuvant treatments. A comparison was made of pre- and post-thaw sperm quality between lymphoma patients and healthy volunteers who applied for sperm donation. This was followed by further assessment of the differences between patients with Hodgkin's disease and non-Hodgkin's lymphoma in terms of sperm variables, clinical parameters and blood hormone concentrations. It was found that patients with lymphoma disease had significantly impaired pre-freeze and post-thaw sperm quality compared with that of healthy volunteers. Patients with non-Hodgkin's lymphoma had spermatozoa of higher quality than patients with Hodgkin's disease. No differences were found in the clinical or hormonal parameters between these two groups. As expected, reduced testicular size and abnormal testicular consistency were correlated with decreased sperm quality. The mere presence of cancer disease has a direct negative effect on spermatogenesis, which is probably not related to incidental side-effects. A variable degree of impairment should be expected with different categories of cancer.      

The effect of bacillus Calmette-Guérin immunization depends on the genetic predisposition to Th2-type responsiveness

The aim of this study was to investigate whether the effect of bacillus Calmette-Guérin (BCG) immunization on ovalbumin-induced allergic inflammation in a rat model depends on the genetic predisposition to react with a T helper cell (Th) 2-type cytokine response. This study was performed in an inbred Th2-predisposed "asthma prone" rat strain (brown Norway [BN]) and in an outbred nonpredisposed strain (Sprague Dawley [SD]), to differentiate between genetic and environmental factors. BCG decreased numbers of lung eosinophils and macrophages in the SD rat. This effect was not seen in the BN rat. In the BN rat, but not in the SD rat, BCG downregulated levels of total serum IgE. No significant differences were found with respect to frequencies of IFNgamma- or interleukin-4-producing cells in the lung in both rat strains. These results indicate that the degree and pathway of immunomodulatory effect of BCG in two genetically different rat strains is dependent on the genetic predisposition to develop a Th2-type response. Therefore, differences in genotype in relation to environment may result in difference in involvement of contributing pathogenic factors and thus different responsiveness to therapeutic strategies.     

Estimate of Burden and Direct Healthcare Cost of Infectious Waterborne Disease in the United States

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million–12.0 million), results in 601,000 ED visits (95% CrI 364,000–866,000), 118,000 hospitalizations (95% CrI 86,800–150,000), and 6,630 deaths (95% CrI 4,520–8,870) and incurring US $3.33 billion (95% CrI 1.37 billion–8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.     

Recency-Weighted Statistical Modeling Approach to Attribute Illnesses Caused by 4 Pathogens to Food Sources Using Outbreak Data,United States

Foodborne illness source attribution is foundational to a risk-based food safety system. We describe a method for attributing US foodborne illnesses caused by nontyphoidal Salmonella enterica, Escherichia coli O157, Listeria monocytogenes, and Campylobacter to 17 food categories using statistical modeling of outbreak data. This method adjusts for epidemiologic factors associated with outbreak size, down-weights older outbreaks, and estimates credibility intervals. On the basis of 952 reported outbreaks and 32,802 illnesses during 1998–2012, we attribute 77% of foodborne Salmonella illnesses to 7 food categories (seeded vegetables, eggs, chicken, other produce, pork, beef, and fruits), 82% of E. coli O157 illnesses to beef and vegetable row crops, 81% of L. monocytogenes illnesses to fruits and dairy, and 74% of Campylobacter illnesses to dairy and chicken. However, because Campylobacter outbreaks probably overrepresent dairy as a source of nonoutbreak campylobacteriosis, we caution against using these Campylobacter attribution estimates without further adjustment.     

Inability to Work Fulltime,Prevalence and Associated Factors Among Applicants for Work Disability Benefit

Journal of Occupational Rehabilitation - Purpose Inability to work fulltime is an important outcome in the assessment of workers applying for a disability benefit. However, limited knowledge is...     

Clinical thinking and decision-making in practice. A child with dyspnea and excess pleural fluid

Pleural fluid was diagnosed on an X-ray in a 9-month-old boy with acute dyspnoea without fever. Thoracentesis showed exudate and the patient was diagnosed as having empyema and was treated with continuous chest tube drainage and antibiotics. The culture of the pleural fluid was negative. A month after discharge the boy developed recurrent pleural effusion with dyspnoea. A mass in the right hemithorax was found upon additional diagnostic evaluation. Microscopic evaluation of tumour biopsy specimen showed a malignancy. Infantile fibromatosis was diagnosed in a surgical specimen. The patient died after having developed a recurrent tumour. Infectious causes are not likely in a child with pleural fluid without fever. Pleural fluid has to be analysed in transudate or exudate. Exudate requires a complete diagnostic evaluation.     

Recurrent, multiple, calcified soft tissue metastases from osteogenic sarcoma without pulmonary involvement

Osteosarcoma (osteogenic sarcoma) metastasizes primarily to the lung. With the introduction of neoadjuvant chemotherapy as part of the treatment, the overall and disease-free survival rates have dramatically improved. In this case report, a young man with multiple soft tissue and bone metastases, including a rare large bone-forming retroperitoneal metastasis, is described. Despite the extensive extrapulmonary metastases, the patient did not develop pulmonary metastases in the 4 years following initial presentation of the primary tumour. Received: 16 December 1998 Revision requested: 14 January 1999 Revision received: 30 July 1999 Accepted: 1 August 1999     

Migration of dendritic cells to the draining lymph node after allogeneic or congeneic rat skin transplantation

BACKGROUND: After transplantation, donor dendritic cells (DC) migrating to the draining lymph node of the recipient are thought to play an important role in the initiation of graft rejection. In this study, we compared the in vivo migration of DC after allogeneic skin transplantation with that after congeneic skin transplantation. METHODS: A rat model was used with the PVG-RT7b rats as donor animals. These rats have leukocytes bearing an epitope of the leukocyte common antigen that can be recognized by the monoclonal antibody His 41. The cells of the allogeneic (ACI) and congeneic (PVG) recipient animals do not express this marker. RESULTS: In both recipient rat strains, graft-derived His 41+ DC could be detected in the T cell areas of the draining lymph nodes after skin transplantation. However, the number of migrated His 41+ cells present was lower in the allogeneic recipients. Similar results were obtained when skin DC isolated from the PVG-RT7b rats were injected subcutaneously into the hind footpads of allogeneic and congeneic recipients. Although the numbers of migrated His 41+ DC present were lower, the lymph nodes of the allogeneic recipients were much more enlarged and the grafts were rejected which did not occur in the congeneic recipients. CONCLUSIONS: The presence of donor-derived DC in the graft draining lymph nodes underlines the importance of the direct route of allo-activation. The lower numbers of migrated His 41+ DC in lymph nodes of allogeneic recipients may be the result of killing of the cells after presentation of the allo-antigens to the recipient T cells.