The pathophysiology of chronic subdural hematoma revisited: emphasis on aging processes as key factor

GeroScience - Chronic subdural hematoma (CSH) affects mostly elderly subjects. Previously, pathophysiological concepts suggested that CSH is secondary to degradation of subdural collections of...     

Too little aspirin for secondary prevention after acute myocardial infarction in patients at high risk for cardiovascular events: Results from the MITRA study

Background

A meta-analysis of randomized trials has shown a significant reduction of mortality rate in patients receiving aspirin for secondary prevention after acute myocardial infarction (AMI). However, a significant number of patients do not receive aspirin after AMI. Little is known about why aspirin is withheld or the long-term outcome of these patients today.

Methods

The Maximal Individual Therapy in Acute Myocardial Infarction (MITRA) registry is a multicenter registry of patients with AMI in Germany.

Results

Of 4902 patients, 509 (10%) did not receive aspirin at the time of discharge from the hospital. The mean follow-up period for these patients was 17 months. Relative contraindications to aspirin were significantly associated with the withholding of aspirin (in-hospital bleeding: odds ratio [OR], 3.56; 95% CI, 1.86-6.80; history of peptic ulcer: OR, 2.49; 95% CI, 1.62-3.83). Absolute contraindications to aspirin were rare (2.2%). Other medications of proven benefit were also given less often in these patients (β-blockers: 49.0% vs 61.9%, P <.001; angiotensin-converting enzyme inhibitors: 65.6% vs 70.2%, P = .06; statins: 12.2% vs 15.1%, P = .10). Patients who were not given aspirin were at high risk for vascular events. They were more likely to have a history of prior AMI (OR, 1.34; 95% CI, 1.02-1.79), were in critical clinical condition at admission more often (cardiogenic shock: OR, 1.98; 95% CI, 1.09-3.56; overt heart failure: OR, 1.6; 95% CI, 1.05-2.3), and received acute revascularization less often (OR, 1.32; 95% CI, 1.05-1.67). The 1-year mortality was 2-times higher in patients who did not receive aspirin than in patients who did receive aspirin (16.5% vs 8.3%, P <.001). A significant association of withheld aspirin at discharge with a higher long-term mortality rate was confirmed with multivariate analysis (OR, 1.62; 95% CI, 1.15-2.29).

Conclusions

Ten percent of patients who sustained an AMI did not receive aspirin at the time of hospital discharge. Most of these patients were at high risk for cardiovascular events. Withheld aspirin was significantly associated with higher mortality rate during follow up.     

The mouse Pax21Neu mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney

We describe a new mouse frameshift mutation (Pax2^1Neu) with a 1-bp insertion in the Pax2 gene. This mutation is identical to a previously described mutation in a human family with renal-coloboma syndrome [Sanyanusin, P., McNoe, L. A., Sullivan, M. J., Weaver, R. G. & Eccles, M. R. (1995) Hum. Mol. Genet. 4, 2183–2184]. Heterozygous mutant mice exhibit defects in the kidney, the optic nerve, and retinal layer of the eye, and in homozygous mutant embryos, development of the optic nerve, metanephric kidney, and ventral regions of the inner ear is severely affected. In addition, we observe a deletion of the cerebellum and the posterior mesencephalon in homozygous mutant embryos demonstrating that, in contrast to mutations in Pax5, which is also expressed early in the mid-hindbrain region, loss of Pax2 gene function alone results in the early loss of the mid-hindbrain region. The mid-hindbrain phenotype is similar to Wnt1 and En1 mutant phenotypes, suggesting the conservation of gene regulatory networks between vertebrates and Drosophila.     

A‐Fibers Mediate Cold Hyperalgesia in Patients with Oxaliplatin‐Induced Neuropathy

Cold hyperalgesia is a common side effect of oxaliplatin treatment; still, the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin‐induced acute neuropathy with (n = 6) and without (n = 7) cold hyperalgesia were tested by applying a preferential blockade of peripheral myelinated A‐fiber afferents in combination with quantitative sensory testing. Additionally, an interview‐based questionnaire assessed the severity of symptoms and the impact on daily activities. Results indicate a deficit of cold perception in patients without cold hyperalgesia compared to patients with cold hyperalgesia prior to A‐fiber blockade. In patients with cold hyperalgesia, a preferential blockade of A‐fibers abolished cold hyperalgesia. This suggests that oxaliplatin‐induced cold hyperalgesia is mediated by A‐fibers and that a deficit in A‐fiber function might prevent the development of cold hyperalgesia. The work supports findings in rodents and in human sural nerve biopsies indicating that oxaliplatin interferes with axonal ion conductance in intact A‐fibers by sensitizing potassium and/or sodium channels. Drugs that act on these molecular targets might be of potential value to treat oxaliplatin‐induced cold hyperalgesia.     

High-Dose Menaquinone-7 Supplementation Reduces Cardiovascular Calcification in a Murine Model of Extraosseous Calcification

Cardiovascular calcification is prevalent in the aging population and in patients with chronic kidney disease (CKD) and diabetes mellitus, giving rise to substantial morbidity and mortality. Vitamin K-dependent matrix Gla-protein (MGP) is an important inhibitor of calcification. The aim of this study was to evaluate the impact of high-dose menaquinone-7 (MK-7) supplementation (100 µg/g diet) on the development of extraosseous calcification in a murine model. Calcification was induced by 5/6 nephrectomy combined with high phosphate diet in rats. Sham operated animals served as controls. Animals received high or low MK-7 diets for 12 weeks. We assessed vital parameters, serum chemistry, creatinine clearance, and cardiac function. CKD provoked increased aortic (1.3 fold; p < 0.05) and myocardial (2.4 fold; p < 0.05) calcification in line with increased alkaline phosphatase levels (2.2 fold; p < 0.01). MK-7 supplementation inhibited cardiovascular calcification and decreased aortic alkaline phosphatase tissue concentrations. Furthermore, MK-7 supplementation increased aortic MGP messenger ribonucleic acid (mRNA) expression (10-fold; p < 0.05). CKD-induced arterial hypertension with secondary myocardial hypertrophy and increased elastic fiber breaking points in the arterial tunica media did not change with MK-7 supplementation. Our results show that high-dose MK-7 supplementation inhibits the development of cardiovascular calcification. The protective effect of MK-7 may be related to the inhibition of secondary mineralization of damaged vascular structures.     

Role of prothrombin 19911 A>G polymorphism,blood group and male gender in patients with venous thromboembolism: Results of a German cohort study

Journal of Thrombosis and Thrombolysis - The role of the A&gt;G polymorphism at position 19911 in the prothrombin gene (factor [F] 2 at rs3136516) as a risk factor for venous thromboembolism...     

Occult celiac disease prevents penetrance of hemochromatosis

AIM:To report a patient with C282Y homozygocity,depleted body iron and intestinal atrophy caused by celiac disease (CD) who experienced resolution of the enteropathy with subsequent normalization of iron metabolism upon gluten free diet. METHODS:To obtain information on the tissue distribution and quantitative expression of proteins involved in duodenal iron trafficking,we determined the expression of divalent-metal transporter 1 (DMT1),ferroportin 1 (FP1) and transferrin receptor (TfR1) by means of immunohist-ochemistry and real-time PCR in duodenal biopsies of this patient. RESULTS:Whereas in hereditary hemochromatosis patients without CD, DMT1 expression was up-regulated leading to excessive uptake of iron, we identified a significant reduction in protein ana mRNA expression of DMT1 as a compensatory mechanism in this patient with HH and CD. CONCLUSION:Occult CD may compensate for increased DMT1 expression in a specific subset of individuals with homozygous C282Y mutations in the hemochromatosis (HFE) gene,thus contributing to the low penetrance of HH.     

Embolic protection devices for carotid artery stenting: better results than stenting without protection?

AIMS: Carotid artery stenting (CAS) for carotid artery stenoses has become an alternative to carotid endarterectomy. However, CAS itself can cause cerebral ischaemic events. Embolic protection devices (PD) promise to reduce the incidence of these events. METHODS AND RESULTS: From July 1996 to March 2003, 1483 patients from 26 hospitals were included in the prospective CAS Registry of the ALKK study group. A PD was used in 668 of 1483 patients (45%). The use of a PD has grown rapidly over the years and reached 100% in 2003. Patients treated with a PD had prior carotid artery dilatation more often (3.5% versus 1%, p < 0.001), a prior myocardial infarction (34% versus 27.4%, p = 0.007) and a history of arterial hypertension (89.9% versus 78.6%, p = 0.007) compared to patients treated without a PD. A thrombus was more often visible in patients treated under distal protection (16.5% versus 8%, p < 0.001). The use of a PD led to a 10-min longer intervention (45 min versus 35 min median, p < 0.001). Patients treated with a PD had a lower rate of ipsilateral stroke (1.7% versus 4.1%, p = 0.007) and a lower rate of all non-fatal strokes and all deaths (2.1% versus 4.9%, p = 0.004) during the hospital stay. This was confirmed by multiple logistic regression analysis (adjusted OR = 0.45, 95% CI: 0.23-0.91, p = 0.026). A similar reduction could be found for symptomatic as well as asymptomatic carotid artery stenoses. CONCLUSION: Since 1996 there has been a steady increase in the use of PDs for CAS, with a 100% use in 2003. The use of a PD may lower the rate of ipsilateral strokes during CAS.