Independent risk factor for moderate to severe internal carotid artery stenosis: T786C mutation of the endothelial nitric oxide synthase gene

BACKGROUND: NO synthesized from L-arginine by the constitutive endothelial NO synthase (eNOS) plays a key role in the atherosclerotic process. We investigated whether common variants in the NOS3 gene (a T786C mutation in the 5' flanking region and the polymorphism on exon 7 that produced the Glu298Arg polymorphism in the protein) are associated with an increased risk of moderate to severe internal carotid artery (ICA) stenosis. METHODS: We studied 88 patients consecutively operated for ICA stenosis and 133 healthy controls. A T786C mutation in the 5' flanking region and the polymorphism in exon 7 that produces the Glu298Asp polymorphism in the protein were explored by PCR and fluorescent probe analysis. RESULTS: Genotype distribution was significantly different between patients and controls only for T786C, the CC genotype frequency being 26% and 13%, respectively [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.14-4.46; P = 0.018]. Moreover, the CC genotype was significantly more frequent in a subgroup of patients with ulcerative plaques compared with patients with nonulcerative lesions (44% vs 17%; OR, 3.82; 95% CI, 1.79-8.14; P = 0.003). Multiple logistic regression analysis using the most frequent risk factors and the eNOS gene variant showed that the CC genotype is an independent risk factor for ICA stenosis (P = 0.023). CONCLUSION: C allele homozygosity in position 786 of the eNOS promoter seems to be an independent risk factor for the development of moderate to severe ICA stenosis, especially ulcerative lesions.     

Modifications in SENV DNA detection and/or SENV subtype determination over a prospective follow-up in a cohort of HIV-positive patients: is this a moving target?

SEN virus (SENV) is a new family of single-stranded DNA viruses with eight different strains, A-H. The modifications in SENV DNA detection and subtype distribution were studied over a long-term follow-up (48 +/- 32.5 months) in 52 HIV-infected patients. 46% of the patients in the first sample and 34.6% in the second sample were found to have detectable SENV viremia. While the most prevalent variant in the first sample was found to be genotype A (83.3%), the second sample revealed a broader subtype diversification. Several epidemiological and clinical variables were tested in univariate model for clearance of detectable SENV viremia, but none of them reached statistical significance. In conclusion, a high degree of instability of both SENV DNA detection and subtype distribution in a cohort of HIV-infected patients was suggested, which may have important implications for further studies on both SENV epidemiology and its clinical impact.     

Reduced expression of macrophage-associated antigens on alveolar mononuclear phagocytes from acquired immunodeficiency syndrome

Summary In this study we evaluated the phenotype of alveolar mononuclear phagocytes recovered from the bronchoalveolar lavage fluid of 24 patients with human immunodeficiency virus infection (AIDS-related complex 8 patients, AIDS 16 patients) and 8 healthy individuals by using a panel of monoclonal antibodies known to react with tissue macrophages, in combination with a flow cytometer. The results showed that 90% of patients with AIDS present a marked reduction in the expression of several antigenic determinants (in descreasing order: CD68, CD36, CR1, CD11c, HLA-DR). The levels of antigen expression by flow cytometry seem to decline with disease progression, showing the most dramatic perturbations in patients with full-blown AIDS associated with pulmonary infections (especiallyPneumocystis carinii pneumonia) and lower peripheral CD4 lymphocyte counts. In contrast, patients with AIDS-related complex or AIDS without histological or cultural evidence of pulmonary involvement showed, respectively, only minimal or medium antigenic decreases. However, only a minor proportion (16%, 20%, 20%, 25%, and 25% respectively) of human immunodeficiency virus infected patients (mostly with AIDS) had a significant reduction of the levels of CD4, CD14, CD45R, CD11b, and CD16 antigens in the alveolar macrophages. Since macrophages play a central role in the pathogenesis of AIDS, it may be postulated that the loss of various phenotypic markers on alveolar mononuclear phagocytes (some of them known for their important immunoregulatory actions) could have an important part in the pathogenesis of human immunodeficiency virus induced immunosuppression, and thereby condition the abnormal susceptibility to pulmonary diseases typical of human immunodeficiency virus-infected patients.     

Middle cerebral artery peak systolic and ductus venosus velocity waveforms in the hydropic fetus.

OBJECTIVE: The purpose of this study was to assess whether Doppler assessment of the middle cerebral artery (MCA) peak systolic velocity (PSV) and ductus venosus (DV) velocity waveforms during sonography of hydropic fetuses may specify the cause of fetal hydrops. METHODS: A level II sonographic examination was performed in 16 hydropic fetuses, and the MCA PSV and DV velocity waveforms were assessed. The MCA PSV values divided hydropic fetuses into anemic (group 1) and nonanemic (group 2) fetuses. In group 2 fetuses, the DV was defined as normal or abnormal. Sonographic examination and Doppler assessment of these vessels specified the cause of hydrops and indicated the use of specific investigations for diagnosing the etiology of fetal hydrops. RESULTS: Seven of 16 fetuses had MCA PSV values greater than 1.50 multiples of the median (group 1). Nine of 16 fetuses had normal MCA PSV values (group 2); among them, 7 of 9 had either absent or reversed flow in the DV, and 2 had a normal DV. In group 1, the cause of fetal anemia was investigated by maternal serum tests, and 5 cordocentesis procedures were performed. In group 2, 7 of 9 fetuses had reversed flow in the DV, which suggested a cardiac abnormality confirmed by echocardiography. Five cordocentesis procedures were performed for fetal karyotype, and in 2 fetuses, the cause of hydrops was idiopathic. CONCLUSIONS: Our data suggest that assessment of the MCA PSV and DV velocity waveforms in the hydropic fetus may further our knowledge of the etiology of hydrops and may indicate which investigations among the many available should be used for diagnosing the cause of fetal hydrops.     

Ausência de associação entre os polimorfismos do gene interleucina-18 e artrite reumatoide

ObjectiveTo assess the association of the polymorphisms of the interleukin-18 (IL-18) gene with rheumatoid arthritis (RA) and with risk factors for cardiovascular diseases (CVD).MethodsThis sample comprised 97 patients with RA and 151 healthy controls. In the patients, risk factors for CVD were analyzed, such as cholesterol levels, arterial hypertension, smoking habit, C-reactive protein (CRP) level, and rheumatoid factor. DNA was extracted and the single nucleotide polymorphisms (SNP) at the ?607C/A and ?137G/C positions of the IL-18 gene were assessed in both groups. The Hardy-Weinberg equilibrium (HWE) was calculated and the odds ratio (OR) test performed, considering a 95% CI and P < 0.05.ResultsThe frequencies of the ?607A allele in patients with RA and in controls were 0,443 and 0.424, respectively, and of the ?137C allele, 0.304 and 0.291, respectively. The genotype frequencies were in HWE, except for controls in the ?137 locus (P = 0.006). Association of the polymorphisms of the IL-18 gene was found with neither RA nor risk factors for CVD, including cholesterol level and CRP (P > 0.05). In addition, more smokers were found among patients with RA as compared with controls (OR = 1.691; P = 0.088), and the CRP levels were slightly higher in patients who smoked than in patients who did not (OR = 2.673; P = 0.061).ConclusionsIn this sample of patients with RA in the South of Brazil, association of the polymorphisms of the IL-18 gene was observed with neither RA nor risk factors for CVD.     

Laparoscopic approach in perforated appendicitis: increased incidence of surgical site infection?

Background

The role of laparoscopy in the setting of perforated appendicitis remains controversial. A retrospective study was conducted to evaluate the early postoperative outcomes of laparoscopic appendectomy (LA) compared to open appendectomy (OA) in patients with perforated appendicitis.

Methods

A total of 1,032 patients required an appendectomy between January 2005 and December 2009. Among these patients, 169 presented with perforated appendicitis. Operation times, length of hospital stay, overall complication rates within 30 days, and surgical site infection (SSI) rates were analyzed.

Results

Out of the 169 evaluated patients, 106 required LA and 63 OA. Although operation times were similar in both groups (92 ± 31 min for LA vs. 98 ± 45 for OA, p = 0.338), length of hospital stay was shorter in the LA group (6.9 ± 3.8 days vs. 11.5 ± 9.2, p < 0.001). Overall complication rates were significantly lower in the LA group (32.1 vs. 52.4 %, p < 0.001), as were incisional SSI (1.9 vs. 22.2 %, p < 0.001). Organ/space SSI rates were similar in both groups (23.6 % after LA vs. 20.6 % after OA, p = 0.657).

Conclusions

For perforated appendicitis, LA results in a significantly shorter hospital stay, fewer overall postoperative complications, and fewer wound infections compared to OA. Organ/space SSI rates were similar for both procedures. LA provides a safe option for treating patients with perforated appendicitis.     

"Without hope it doesn't work". An empirical investigation about the importance of hope for caregivers in South Tyrol (italy)

Recent studies on the relevance of hope in nursing have clearly shown that we are dealing with an emotional need as well as a basic coping strategy for both patients and their families. In German speaking countries we are still lacking studies analysing how family caregivers live hope. It is the aim of this study to find out more about the importance of hope for caregivers in South Tvrol (Italy). The research is based on twelve narrative interviews with family caregivers who have been looking after their needy relatives in their own homes for years. Data analysis occurred via qualitative content analysis. The results show the vital role hope plays in coping with caring situations over years. The way caregivers define hope, their objects, and sources of hope as well as their experiences of hope determines how they organise and manage daily and future situations. Hope is defined as love, trust, or blessing. The various objects of hope revolve around doing the very best for the patients and the respective families. Family, faith, and life experience are the main sources of hope and strength. Caregivers' experience of hope is characterised by ups and downs, in other words by periods determined by confidence and periods determined by worries. Hope is both a prerequisite for and a result of successful coping.     

Prognostic Value of Disseminated Tumor Cells in the Bone Marrow of Patients with Operable Primary Breast Cancer: A Long-term Follow-up Study

Background

Detection of disseminated tumor cells (DTC) in primary breast cancer (BC) patients’ bone marrow (BM) seems to be a surrogate marker of tumor spread and an independent prognostic factor for disease-free and overall survival.

Methods

Here we present the largest single-center cohort of patients (n = 1378) with the longest observation time (median 82.0 months). Immunocytochemical staining was performed using murine monoclonal antibody 2E11 with the avidin–biotin complex technique.

Results

At primary surgery, 49 % of patients showed MUC-1 positive cells inside their BM. Patients without BM DTC had significantly more often T1-tumors (P = 0.007) with less often affected axillary lymph nodes (P < 0.001). We observed a significantly higher incidence of distant metastases in DTC positive patients (P < 0.001). This leads to a reduced disease-free survival (P < 0.0001). Furthermore, in DTC positive patients there was a higher mortality rate and, accordingly, a reduced overall survival (P < 0.0001).

Conclusions

Due to the presence of BM DTC, patients with a clinically poorer outcome can be identified at primary surgery. We therefore suggest that DTC analysis can be used as a prognostic factor and monitoring tool in clinical trials. Future study concepts relating to DTC should aim at identification of BC patients who may profit from adjuvant systemic therapy.     

Characterization of Responder Profiles for Cardiac Resynchronization Therapy through Unsupervised Clustering of Clinical and Strain Data

1. Download : Download high-res image (249KB)
2. Download : Download full-size image