Using ankle-brachial index to detect peripheral arterial disease: prevalence and associated risk factors in a random population sample

Background and aimThe ankle-brachial index (ABI) is being used increasingly to diagnose peripheral arterial disease (PAD) that predicts cardiovascular morbidity and mortality. The aim of this study is to determine the prevalence of PAD and associated risk factors in a Spanish random population sample of age ≥40.Methods and resultsPAD is defined as an ABI < 0.9 in either leg. 784 participants of age ≥40 were randomly selected in a Spanish province. 55.4% of them were female. The prevalence of PAD in this sample was 10.5% (95% confidence interval (CI) 8.4–12.8); 9.7% in females and 11.4% in males. In logistic regression analyses, adjusted for age and gender, smoking per 10 pack-years (odds ratio (OR) 1.40, 95% CI 1.23–1.58), hypertension (OR 1.85, 95% CI 1.05–3.28), hypercholesterolemia (OR 1.76, 95% CI 1.04–2.98), and diabetes (OR 1.80, 95% CI 1.04–3.11) were positively associated with prevalent PAD. More than 91% of persons with PAD had one or more cardiovascular disease risk factors.ConclusionsWe conclude that in our study hypertension, hypercholesterolemia, diabetes mellitus and smoking are associated with PAD. The majority of individuals with PAD had at least one important cardiovascular risk factor advanced enough to be considered eligible for an aggressive treatment.     

The dual dopamine‐glutamate phenotype of growing mesencephalic neurons regresses in mature rat brain

Coexpression of tyrosine hydroxylase (TH) and vesicular glutamate transporter 2 (VGLUT2) mRNAs in the ventral tegmental area (VTA) and colocalization of these proteins in axon terminals of the nucleus accumbens (nAcb) have recently been demonstrated in immature (15‐day‐old) rat. After neonatal 6‐hydroxydopamine (6‐OHDA) lesion, the proportion of VTA neurons expressing both mRNAs and of nAcb terminals displaying the two proteins was enhanced. To determine the fate of this dual phenotype in adults, double in situ hybridization and dual immunolabeling for TH and VGLUT2 were performed in 90‐day‐old rats subjected or not to the neonatal 6‐OHDA lesion. Very few neurons expressed both mRNAs in the VTA and substantia nigra (SN) of P90 rats, even after neonatal 6‐OHDA. Dually immunolabeled terminals were no longer found in the nAcb of normal P90 rats and were exceedingly rare in the nAcb of 6‐OHDA‐lesioned rats, although they had represented 28% and 37% of all TH terminals at P15. Similarly, 17% of all TH terminals in normal neostriatum and 46% in the dopamine neoinnervation of SN in 6‐OHDA‐lesioned rats were also immunoreactive for VGLUT2 at P15, but none at P90. In these three regions, all dually labeled terminals made synapse, in contradistinction to those immunolabeled for only TH or VGLUT2 at P15. These results suggest a regression of the VGLUT2 phenotype of dopamine neurons with age, following normal development, lesion, or sprouting after injury, and a role for glutamate in the establishment of synapses by these neurons. J. Comp. Neurol. 517:873–891, 2009. © 2009 Wiley‐Liss, Inc.     

Assessment of myocardial viability in postinfarction and indications of revascularization

Following myocardial infarction, it is indispensable to investigate the viability of the myocardium when signs of left ventricular dysfunction are predominant, so as to distinguish between permanent ventricular dysfunction and dysfunction that can be improved with treatment. Several imaging techniques are capable of detecting viable hibernating myocardium; each addresses a specific aspect of the problem. Stress echocardiography and nuclear imaging techniques remain the most widely used even though new techniques like MRI may be better for detecting myocardial viability. Remote myocardial revascularization can lead to regression of the remodeling of the left ventricle, which occurs after infarction causing latent or patent cardiac failure, and thus to recovery of left ventricular function. It is therefore indicated, in association with optimal medical treatment, in patients selected by viability explorations. The best revascularization method (angioplasty or surgery) should be proposed according to scientific knowledge, the comorbidities, and the patient’s choice.     

Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic renal cell carcinoma

OBJECTIVES

To analyse the implications of DNA mismatch repair genes hMLH1 and hMSH2 in sporadic renal cell carcinoma (RCC).

MATERIALS AND METHODS

Specimens of tumour and healthy renal tissue were collected from 89 patients treated for sporadic RCC. Another 95 blood samples taken from individuals with no history of cancer were also analysed. After DNA extraction and PCR amplification, microsatellite instability (MSI) was determined using the Bethesda microsatellite panel, two exonic microsatellites of the TGFbRII and BAX genes, and the microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis of complete coding region of hMLH1 and hMSH2 genes was performed.

RESULTS

MSI and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of heterozygosity (LOH) was common among patients with RCC, particularly in microsatellite D3S1611 (34.9%). Mutations were identified in eight patients: K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in gene hMSH2. The mutations also appeared in healthy renal tissue and therefore, were considered as germline DNA sequence variations. There were G322D and K618A changes in >1% of the healthy control subjects, suggesting that they are DNA polymorphisms.

CONCLUSIONS

Our data show that loss of function of both hMLH1 and hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation in their exons. However, LOH indicated that chromosomal instability affecting large fragments of DNA was the main genetic alteration we detected associated with RCC.     

Patterns of Surgical Treatment for Women Diagnosed with Early Breast Cancer in Queensland

BACKGROUND: Australian women with early breast cancer should be given the choice between breast-conserving surgery (BCS) or mastectomy. This is the first Australian study to report on patterns of surgical care specifically for early breast cancer at a population level. METHODS: Two population-based routine data collections were linked to obtain surgical treatment information for breast cancer cases diagnosed in 2004 in Queensland, from which we identified 1274 cases of early female breast cancer. Logistic regression was used to assess the likelihood of female breast cancer patients having mastectomy, BCS, and axillary node dissection, after adjusting for patient and hospital demographics, tumor size, and comorbidities. RESULTS: Three-quarters (77%) of women had BCS, 29% had a mastectomy, and 86% had dissection of the axillary lymph nodes. The likelihood of women having mastectomy was higher among women living in rural areas, those treated in public hospitals, and women who had comorbidities of anemia or heart failure. In contrast, BCS was more likely for women treated in private hospitals or hospitals with high surgical caseload. Heart failure decreased the likelihood of BCS. Having an axillary node dissection was more likely among younger women and those treated in high caseload hospitals. CONCLUSION: The observed differentials in surgical treatment for early breast cancer patients suggest that access issues may have contributed to the decision-making process. Understanding the reasons why women with early breast cancer choose a certain treatment strategy should be a focus of future research.