Prognostic factors in patients with active non-variceal upper gastrointestinal bleeding

Background and study aims

Acute upper gastrointestinal bleeding is one of the main causes of hospitalisation. The purpose of this study was to determine the prognostic factors in non-variceal upper gastrointestinal bleeding.

Peak bone mass of Iranian population: the Iranian Multicenter Osteoporosis Study.

Osteoporosis is a major public health problem in the Western countries and is projected to have a similar impact in the Middle East. It has been suggested that peak bone mineral density (BMD), a major determinant of osteoporotic fractures later in life, may be lower in this part of the world compared with the Western world. The purpose of the Iranian Multicenter Osteoporosis Study was to determine peak bone mass in a randomly chosen sample of healthy Iranian subjects. A total of 5201 participants (2340 males, mean age 42.7+/-13.8) were recruited based on randomized clustered sampling from all regions of five major cities across the country. In women, peak lumbar BMD (1.182+/-0.127 g/cm2) occurred in the 29- to 33-yr age group, whereas peak total femur BMD (1.006+/-0.126 g/cm2) occurred in the 32- to 36-yr age group. In men, peak lumbar BMD (1.181+/-0.153 g/cm2) and femoral BMD (1.096+/-0.159 g/cm2) both occurred in the 20- to 24-yr age group. When standardized to mg/cm2 units using established formulas, Iranian peak bone mass values are comparable with that of Western countries and are generally higher than that of Eastern Asian and Middle Eastern countries.     

Primary carcinoma of gallbladder in Yazd, Iran: A 14-year study (1992–2006)

Aim: To investigate the clinico‐pathological profile and stage of disease at presentation of patients with carcinoma of the gallbladder diagnosed during 1992–2006 in Iran. Methods: During this study period 34 consecutive patients with gallbladder carcinoma were identified using a pathology‐based tumor database. The data extracted for each study patient included their gender, age at diagnosis, signs and symptoms, presence of gallstones and histopathological pattern of the gallbladder carcinoma and the UICC/AJCC TNM staging system was used for labeling the stages of the disease. Results: The median age of the 34 patients studied was 69.50 with most between 61 and 70 years of age. The age range of the men was between 53 and 80 years with a median age of 71.50 years and that of the women was between 33 and 79 years with a median age of 68.50 years. The most common symptom was pain in the right hypochondrium. More women had gallstones (15/34) than men (3/10). Adenocarcinoma was the most common histopathological type (91.18%) with the commonest subtype being papillary (47.06%). Eighteen patients had stage IB and stage IIA (52.94%) carcinomas whereas stages IIB and III were observed in six (17.6%) and seven cases (20.6%), respectively. Only three cases (8.82%) were seen in stage IV. The follow up of gall bladder carcinoma (GBC) patients in this study ranged from 6 to 60 months. However, there was a progressive reduction of patients attending follow‐up oncology clinic, particularly by those who had stages III and IV of the disease. Conclusion: Most patients (52.94%) presented with early disease (stage IB and IIA) which carries a good prognosis. Early detection of GBC and a national consensus for the evidence‐based management of GBC in Iran should be the major components of a strategy aimed at improving therapeutic outcome.     

Human cytomegalovirus infection up-regulates interleukin-8 gene expression and stimulates neutrophil transendothelial migration.

Virus-induced alterations in the cellular expression of chemokines may be important in directing the migration of specific leucocyte subsets to sites of infection, thereby playing a pivotal role in viral pathogenesis. We show here that cytomegalovirus (CMV) infection of human fibroblasts resulted in significantly increased expression of the C-X-C or alpha-chemokine interleukin-8 (IL-8), at both the mRNA and protein levels. Increased IL-8 production was seen following infection with the high passage laboratory CMV strains AD169, Towne, or Davis, as well as the low passage clinical CMV isolates Toledo or C1F. The increase in IL-8 production had functional consequences, as demonstrated by the ability of supernatants from CMV-infected fibroblasts to significantly enhance neutrophil transendothelial migration. The latter was independent of alterations in adhesion molecule expression on the endothelial cells, and was abrogated by neutralizing antibodies specific for IL-8. Direct infection of endothelium with the endothelial cell-tropic CMV strain C1FE, also resulted in enhanced neutrophil transendothelial migration. Neutrophils play an important role in the dissemination of CMV throughout the body, and thus CMV-induced neutrophil recruitment would be expected to enhance CMV dissemination. Increased production of chemokines in response to CMV infection could also disrupt the fine balance between a beneficial and a destructive immune response, thereby potentially contributing to pathology.     

Effects of racist provocation and social support on cardiovascular reactivity in african american women

It has been speculated that exposure to the chronic stress of racism contributes to the high rates of hypertension among African Americans. Social support may buffer the effects of stress on cardiovascular (CV) health by attenuating stress-induced CV responses that have been linked to hypertension. In this study we investigated the effects of racism and social support on CV reactivity in African American women. Participants showed greater increases in CV and emotional responses while responding and listening to racist provocation. Augmented blood pressure (BP) persisted through recovery following racial stress. Participants receiving no support showed the greatest increases in anger during racist provocation. No significant effects were seen for support on CV reactivity. These results provide some of the first evidence that interactive confrontation with racism elicits significant increases in CV reactivity and emotional distress. Furthermore, individuals receiving less support may be at greater risk for the potentially health-damaging effects of racial stress. These findings may have significant implications for the health of African Americans.     

Haplotypic association of DDAH1 with susceptibility to pre-eclampsia

Association between pre-eclampsia (PEE1) and the dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 genes, which play a role in the regulation of nitric oxide synthesis and release, was studied. In a case-control study design single nucleotide polymorphisms (SNPs) were determined at eight sites in the DDAH1 gene and at one site (Pro231Pro) in the DDAH2 gene from 132 women with pre-eclampsia and 112 healthy controls. Three SNPs in the DDAH1 gene were associated with pre-eclampsia, showing complete linkage disequilibrium with each other, but none of the associations in the allele or genotype data reached statistical significance in either of the genes after the correction for multiple testing. Haplotype frequencies were estimated using a population based on a maximum likelihood method (EM algorithm). Four common DDAH1 haplotypes were present and a significant association of haplotypes H2 and H3 with pre-eclampsia (P=0.03) was found. The risk of pre-eclampsia was greatest in individuals (odds ratio: 3.93; 95% confidence interval: 1.54-9.99) who had two copies of the high-risk haplotypes (H2 or H3). The observed haplotypic association provides the first evidence of the importance of DDAH1 polymorphisms in pre-eclampsia susceptibility.     

Controlled study of Escherichia coli diarrheal infections in Bangladeshi children.

Diarrheal diseases are highly prevalent in Bangladesh. However, the relative contribution of diarrheagenic Escherichia coli organisms--those that are enterotoxigenic (ETEC), enteropathogenic (EPEC), enteroinvasive, enterohemorrhagic, enteroaggregative, and diffuse adherent--to diarrhea in Bangladeshi populations is not known. With DNA probes specific for these diarrheagenic E. coli strains, we analyzed fecal E. coli from 451 children up to 5 years of age with acute diarrhea seeking treatment at a Dhaka hospital and from 602 matched control children without diarrhea from July 1991 to May 1992. Enteroinvasive E. coli was not isolated from any children; enterohemorrhagic E. coli was not isolated from any diarrheal children but was isolated from five control children; enteroaggregative and diffuse adherent E. coli strains were isolated with similar frequencies from children with and without diarrhea, thereby showing no association with diarrhea; ETEC was significantly associated with diarrhea in the diarrheal children as a whole and especially in the age groups of 0 to 24 months and 37 to 48 months (further analysis suggests an association with diarrhea for the heat-stable toxin only and for both heat-labile- and heat-stable-toxin-producing ETEC only); and EPEC was significantly associated with diarrhea in the diarrhea group as a whole and particularly in infants up to 1 year of age. Further analysis suggested that EPEC strains of only the traditional serogroups were significantly associated with diarrhea. ETEC and EPEC infections peaked during warm months. Our data thus suggest that EPEC and ETEC are important causes of acute diarrhea in children in this setting.     

Antigen-specific T cell suppression by human CD4+CD25+ regulatory T cells

Anergic/suppressive CD4+CD25+ T cells have been proposed to play an important role in the maintenance of peripheral tolerance. Here we demonstrate that in humans these cells suppress proliferation to self antigens, but also to dietary and foreign antigens. The suppressive CD4+CD25+ T cells display a broad usage of the T cell receptor Vbeta repertoire,suggesting that they recognize a wide variety of antigens. They reside in the primed/memory CD4+CD45RO+CD45RB(low) subset and have short telomeres, indicating that these cells have the phenotype of highly differentiated CD4+ T cells that have experienced repeated episodes of antigen-specific stimulation in vivo. This suggests that anergic/suppressive CD4+CD25+ T cells may be generated in the periphery as a consequence of repeated antigenic encounter. This is supported by the observation that highly differentiated CD4+T cells can be induced to become anergic/suppressive when stimulated by antigen presented by non-professional antigen-presenting cells. We suggest that besides being generated in the thymus, CD4+CD25+ regulatory T cells may also be generated in the periphery. This would provide a mechanism for the generation of regulatory cells that induce tolerance to a wide array of antigens that may not be encountered in the thymus.     

Carbonic anhydrase gene expression in CA II-deficient (Car2−/−) and CA IX-deficient (Car9−/−) mice

Using real-time PCR and immunohistochemistry, we have examined the expression of carbonic anhydrase isozymes (CA) I, II, III, IV, IX, XII, XIII and XIV in the brain, kidney, stomach and colon of the wild-type, CA II-deficient ( Car2^−/− ), and CA IX deficient ( Car9^−/− ) mice. The expression of Car4, Car12, Car13 and Car14 mRNAs did not show any significant deviations between the three groups of mice, whereas both groups of CA deficient mice showed decreased expression levels of Car1 in the colon and Car3 in the kidney. The Car2 mRNA level was greatly reduced but not completely abolished in all four tissues from the Car2^−/− mice in which no CA II protein was expressed. Sequencing the Car2 cDNA isolated from C57BL6 Car2^−/− mice revealed two nucleotide differences from the wild-type C57BL6 mice. One is a silent polymorphism found in Car2 mRNA from wild-type DBA mice, which is the strain that provided the original mutagenized chromosome. The second change is a mutation that causes prematurely terminated translation at codon 155 (Gln155X). Car9 mRNA and CA IX protein expression levels were up-regulated about 2.5- and 3.6-fold, respectively, in the stomach of the Car2^−/− mice. These results suggest that the loss of function of cytosolic CA II in the stomach of Car2^−/− mice leads to up-regulation of an extracellular CA, namely CA IX, which is expressed on the cell surface of the gastric epithelium.     

Bone mineral density is related to blood pressure in men

The aim of this study was to determine the relationships between bone mineral density (BMD) and blood pressure in 214 men, age 20–76. BMD measurements were done by dual X‐ray absorptiometry using a Lunar DPXMD densitometer at the lumbar spine (L2–L4) and different femoral regions. Systolic (SBP) and diastolic (DBP) blood pressure were measured using an MPC‐350 sphygmomanometer. Physicians gathered demographic data and participants' dietary intake of calcium were determined by using food frequency questionnaires. After adjusting for age, body mass index, dietary calcium, and exercise history, multiple linear regression models showed that DBP was negatively related to femoral neck BMD (β = ?0.145, P = 0.032) and just shy of significant association with femoral neck BMC (β = ?0.114, P = 0.079). SBP was correlated with femoral neck (r = ?0.171, P = 0.012) and Ward's (r = ?0.186, P = 0.006) BMD but not after adjusting for possible confounders. Further studies are needed to determine whether elevated blood pressure is causally related to the development of low bone mass. Am. J. Hum. Biol. 16:168–171, 2004. © 2004 Wiley‐Liss, Inc.