The T-786C endothelial nitric oxide synthase genotype is a novel risk factor for coronary artery disease in Caucasian patients of the GENICA study

OBJECTIVES: We investigated the association of polymorphisms in the promoter region and exon 7 endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD). BACKGROUND: Endothelial dysfunction foretells cardiovascular events and can be genetically determined. METHODS: We genotyped for the promoter (T(-786)C) and exon 7 (Glu298Asp, G(894)T) polymorphisms in 1,225 subjects; 1,106 were consecutive patients undergoing coronary angiography and 119 control subjects without any cardiovascular risk factors. Genotyping was performed with melting curve analysis of polymerase chain reaction products from allele-specific acceptor and donor probes that were 5'- and 3'-end labeled with LCRed640 and fluorescein, respectively; CAD was assessed by quantitative coronary angiography. We performed multiple logistic regression analysis for the effect of the T(-786)C, the missense Glu298Asp variant, and other coronary risk factors on two- and three-vessel CAD. RESULTS: The overall genotype distribution of T(-786)C (CC = 17.7%, CT = 40.4%, and TT = 41.9%) and Glu298Asp (GG = 43.3%, GT = 37.0%, and TT = 19.7%) was consistent with the Hardy-Weinberg equilibrium. The regression analysis showed that the T(-786)C, but not the missense Glu298Asp variant, significantly predicted CAD, independent of other risk factors. Compared with TT homozygous, subjects carrying the C allele had a significant (p = 0.002) increase in the odds ratio of harboring two- or three-vessel CAD of 1.672 (95% confidence interval, 1.062 to 2.527). A subgroup analysis confirmed this effect of the T(-786)C polymorphism in men (p = 0.007), cigarette smokers (p = 0.001), subjects older than 60 years of age (p = 0.007), with hypercholesterolemia (p = 0.011), low high-density lipoprotein cholesterol (p = 0.006), and overweight or with obesity (p = 0.041). CONCLUSIONS: The C allele at the T(-786)C endothelial nitric oxide synthase polymorphism is associated with a higher risk of multivessel CAD in Caucasians.     

Quantitative ultrasound for the assessment of osteopenia in preterm infants

OBJECTIVE: To evaluate the potential role of quantitative ultrasound (QUS) investigation in assessing the osteopenia of prematurity. DESIGN: QUS parameters measured at the time of discharge were related to the anthropometric characteristics and age (postnatal and gestational) of 51 (34 female and 17 male) preterm infants fed fortified human milk. METHODS: QUS evaluation was performed at the humerus (h) by measuring two parameters: ultrasound velocity (hSOS, in m/s) and bone transmission time (hBTT, in micros). A group of 43 term infants (29 female and 14 male) was also evaluated. RESULTS: In preterm infants, significant correlations were found for hSOS and hBTT vs gestational age (r=0.504, 0.477, P<0.0001), length (r=0.641, 0.594, P<0.0001) and weight (r=0.580, 0.562, P<0.0001) at birth, and length (r=0.341, 0.332, P<0.05) and weight (r=0.331, r=0.362, P<0.05) at QUS measurement. In preterm infants, both QUS parameters were negatively correlated with age (r=-0.536, P<0.0001, r=-0.443, P<0.001) and were significantly lower than in the term infants (hSOS: 1664+/-42 m/s vs 1734+/-28 m/s, P<0.0001; hBTT: 0.58+/-0.24 micros vs 1.06+/-0.15 micros, P<0.0001) even when adjusted for body length (P<0.05). In preterm infants, hSOS was also negatively correlated with postconceptional age (r=-0.322, P<0.05). CONCLUSIONS: This study suggests that bone mineral accrual is mainly determined by the development in utero, and that prematurity induces a halt in the bone development process in the early postnatal period. QUS parameters are correlated with the severity of prematurity and might therefore have clinical applications when bone maturation in early life needs to be determined.     

Systematic coronary stenting after failed thrombolysis in high-risk patients with acute myocardial infarction: procedural results and long-term follow-up

BACKGROUND: Stenting in acute myocardial infarction (AMI) represents a feasible and effective revascularization strategy. However, very little information is available for patients who receive a stent after failed thrombolysis (so-called 'rescue' stenting). METHODS: We analysed the procedural results and the 2-year follow-up of all consecutive patients with moderate-to-large AMI treated with rescue stenting in the period 1996-2001. RESULTS: The study cohort includes 123 patients (mean age 60+/-12 years, 78% men). Coronary angiography showed multivessel disease in 47% of patients; the infarct-related vessel was the left anterior descending coronary artery in 47%, the right coronary artery in 41%, the left circumflex coronary artery in 9.5% and a saphenous vein graft in 2.5%. Baseline Thrombolysis in Myocardial Infarction (TIMI) flow was grade 0-1 in 65% and grade 2 in 25%. Coronary stenting was attempted in all 123 patients and was successful in 119 out of 123 (96.7%); abciximab was used in 57 out of 123 (46%) and intra-aortic balloon pumping in 35 out of 123 (28%). At the end of the procedure, TIMI 3 flow was obtained in 104 out of 123 (85%) and TIMI 2 flow in 14 out of 123 (11%). There were 10 in-hospital deaths and four late deaths, with a long-term survival of 88.6%. This figure increases to 95.2% if patients presenting with cardiogenic shock are excluded. A new revascularization procedure was performed in 21% of discharged patients (in the target vessel for 12% and in non-target vessels for 9%). Overall, event-free survival at 2 years was 69%. At multivariate analysis, independent predictors of survival were age (P=0.014) and ejection fraction (P=0.006). CONCLUSIONS: This report represents one of the first series concerning long-term follow-up after rescue stenting. The main results include a high procedural feasibility, a low late mortality and a target vessel revascularization rate in the range expected with stenting. These data must be viewed as part of the constant effort to optimize revascularization strategies in AMI.     

Significant factors associated with fatal outcome in emergency open surgery for perforated peptic ulcer

AIM: To evaluate the main factors associated with mortality in patients undergoing surgery for perforated peptic ulcer referred to an academic department of general surgery in a large southern Italian city. METHODS: One hundred and forty-nine consecutive patients (M:F ratio=110:39, mean age 52 yrs, range 16-95) with peptic ulcer disease were investigated for clinical history (including age, sex, previous history of peptic ulcer, associated diseases, delayed abdominal surgery, ulcer site, operation type, shock on admission, postoperative general complications, and intra-abdominal and/or wound infections), serum analyses and radiological findings. RESULTS: The overall mortality rate was 4.0%. Among all factors, an age above 65 years, one or more associated diseases, delayed abdominal surgery, shock on admission, postoperative abdominal complications and/or wound infections, were significantly associated (chi2) with increased mortality in patients undergoing surgery (0.0001相似文献   

Mutations of the X-linked lymphoproliferative disease gene SH2D1A mimicking common variable immunodeficiency

Common variable immunodeficiency (CVID) and X-linked lymphoproliferative (XLP) disease are two immunodeficiencies that may share a similar immunological phenotype making differential diagnosis difficult. We report two patients initially diagnosed as affected with CVID who, using molecular analysis, have been subsequently found to be affected with XLP disease. Distinguishing between these two diseases is essential since they have different prognosis, treatment and genetic counselling. CONCLUSION: current techniques, such as genetic analysis of the SH2D1A gene and expression of signalling lymphocyte activation molecule-associated protein, allow a definite diagnosis of X-linked lymphoproliferative disease.     

Genetic polymorphism of the major regulatory element HS-40 upstream of the human alpha-globin gene cluster

The highly conserved 350-bp major regulatory element HS-40 (or alphaMRE) upstream of the human alpha-globin gene cluster is involved in the regulation of alpha-globin gene expression. The study of alphaMRE differences between human populations and the evolution of alphaMRE sequences in mammals may lead to a better understanding of the function and importance of this element in the regulation of expression of the downstream alpha-cluster. Denaturing gradient gel electrophoresis was used to determine the sequence heterogeneity of the alphaMRE region in 276 unrelated individuals, representing seven different populations. Furthermore, we analysed the alpha major regulatory elements of chimpanzee, orang-utan and rhesus monkeys and compared them with the equivalent human and murine sequences. Six different alphaMRE haplotypes (labelled A to F) were found in humans. Haplotype frequencies between the seven populations showed a gradual shift to a higher haplotype A distribution from west to east, being the highest in Indonesians. The African sample shows the largest divergence in haplotypes. Five out of six different haplotypes were present, three of which were exclusively found in Africans. The high prevalence of the haplotype A in humans, together with the conservation of this haplotype in apes, suggests that it is the ancestral one. The alphaMRE fragment appears to be a highly polymorphic marker, which could be used in combination with the regular markers in the alpha-cluster to extend the haplotype and to follow segregation of alpha-thalassaemia genes in population studies more accurately.     

Passive avoidance response in mice infected with Schistosoma mansoni

Schistosomiasis is a parasitic disease of humans and rodents affecting more than 200 million people worldwide. Following the onset of infection, the worms induce granulomas around schistosome eggs in the liver, intestine and central nervous system (both brain and spinal cord), which are likely to cause changes in cognitive functions. In the present study, CD-1 female mice were percutaneously infected with 60 cercariae of Schistosoma mansoni and the effect on the mice's cognitive abilities were assessed by using the passive avoidance learning paradigm both in an early and a late phase of infection (independent groups). The results of the study show that infected animals without brain granulomas (early phase) had impairments in their passive avoidance response, whereas mice with brain granulomas (late phase) behaved as uninfected ones. Moreover, a decreased propensity to start exploration was observed in mice with granulomas in the brain. The results suggest that the murine model of infection may be a useful tool for studying human neuroschistosomiasis.