Homozygosity for the C-->T polymorphism at nucleotide 46 in the 5' untranslated region of the factor XII gene protects from development of acute coronary syndrome

Recently, a C-->T polymorphism at nucleotide 46 in the 5'-untranslated region of the factor XII (FXII) gene was shown to be associated with lower levels of FXII. To study the impact of this polymorphism on the development of an acute coronary syndrome (ACS), we compared 303 patients with ACS and 227 patients with stable coronary artery disease (CAD). In the latter group, 54.2% of individuals carried wild-type FXII:46C, 37.9% were heterozygous FXII:C46T and 7.9% were homozygous for FXII:46T. In contrast, in the ACS group (n = 303), 54.1% were wild-type FXII:46C, 42.6% were heterozygous FXII:C46T and only 3.3% carried the homozygous FXII:46T genotype. The 2.5-fold lower prevalence of the FXII:46T genotype in patients with ACS could indicate a protective effect on the development of ACS (odds ratio = 0.4, 95% CI 0.1-0.9) in patients with pre-existing CAD.     

The expanding clinical spectrum of Anderson-Fabry disease: a challenge to diagnosis in the novel era of enzyme replacement therapy

Anderson-Fabry disease is an X-linked recessive lysosomal storage disease resulting from deficient alpha-galactosidase A activity. The conception of the disease has changed within the last decade. Studies of the last years have shown that the disease is not limited to the classical full-blown manifestation in affected males, which is well known since more than a century, but may also occur in carrier females. The phenomenology may differ in severity and kind of organ manifestation. Cardiac and renal variants with solely disease manifestation of these organs have also been described in an increasing number. It is likely that a spectrum exists regarding alpha-galactosidase A activity in both genders on the one hand, and an additional one regarding the severity and the number of organs affected on the other. The purpose of this review is to sharpen physicians' perception of this disease. Early and accurate diagnosis is mandatory considering that this disorder is now, after introduction of the novel enzyme replacement therapy, a treatable disease.     

Fast Track in der Thoraxchirurgie

Patients undergoing thoracic surgery are threatened by pulmonary complications such as pneumonia and atelectasis. Age, preoperative FEV₁, operative time and extent of resection are predictors for adverse outcome. Reported morbidity after lung resection is as high as 42% and mortality up to 7%. Fast track in thoracic surgery aims at reducing morbidity and mortality rates after lung resection by introducing specific measures into the pre-, intra- and postoperative periods. Basic fast track elements in thoracic surgery are smoking cessation, preoperative physiotherapy, micronutrient supplementation, high thoracic epidural anesthesia, fluid restriction, early mobilization and enteral feeding. The effectiveness of these individual measures has been proven of value in perioperative care, however, evidence on multimodal therapy regimens in thoracic surgery is limited. In particular it remains to be elucidated which patients should be fast tracked in order to improve outcomes.     

Quantification of α-galactosidase activity in intact leukocytes

BackgroundMutations of the α-galactosidase (α-Gal) A gene in Fabry disease lead to a severe disturbance in glycosphingolipid catabolism. The atypical clinical picture of Fabry disease hampers diagnosis, resulting in a delayed start of therapy. Current tests utilize leukocyte lysates to evaluate the activity of α-Gal A. It has never been investigated whether cell homogenisation is necessary.MethodsIsolated leukocyte subsets were incubated with the α-Gal substrate methylumbelliferyl-α-d galactopyranosid (MU-Gal) and substrate conversion was measured by fluorimetry. Specificity of the reaction was evaluated using the α-Gal inhibitor deoxygalactonojirimycin (DGJ). The novel procedure was compared to the standard method. A reference population and Fabry patients were tested.ResultsSubstrate conversion in intact leukocytes was a function of substrate concentration, cell number and time and could be inhibited by DGJ. Monocytes showed the highest enzyme activity among leukocyte populations. The novel procedure highly correlated with the standard method. Both Fabry hemizygotes and heterozygotes showed reduced substrate conversion.ConclusionWe here present a novel sensitive, fast and simple procedure for the evaluation of α-Gal activity suitable to identify enzyme deficiencies in Fabry patients. Furthermore, we show for the first time that leukocyte subtypes have different α-Gal activities.     

Die Auswirkung einer Arteria-carotis-Thrombendarteriektomie auf den pulsatilen okul?ren Blutfluss

Erfolgreiche Thrombendarteriektomien (TEA) der A. carotis interna führen zu einer verbesserten Perfusion im Stromgebiet dieser Arterie. Es ist jedoch schwierig, w?hrend der Operation Aussagen über die zerebrale und okul?re Durchblutung zu treffen.     

The effect of mild therapeutic hypothermia on renal function after cardiopulmonary resuscitation in men

Background: Mild therapeutic hypothermia (MTH) improves neurological outcome in patients after cardiac arrest. From animal and human studies it appears that hypothermia impairs renal function. The aim of this study was to examine the effects of MTH on renal function in humans. Methods: Patients were participants recruited in one of the centres of the hypothermia after cardiac arrest-multicenter trial. We measured serum creatinine and creatinine clearance (C_Cr) within 24 h of MTH, at 4 hourly intervals. Patients were followed for acute renal failure and need for renal supportive therapy for 28 days. Results: We included 60 patients (32 hypothermic, 28 normothermic). Median serum creatinine on admission was [{119 μmol/l (IQR 108–133)} {1.35 mg/dl (IQR 1.22–1.50)}] in hypothermic and [{114 μmol/l (IQR 99–131)} {1.29 mg/dl (IQR 1.12–1.48)}] in normothermic patients, and decreased to [{69 μmol/l (IQR 62–84)} {0.78 mg/dl (IQR 0.70–0.95)}] in the hypothermic group and to [{88 μmol/l (IQR 71–123)} {1.00 mg/dl (IQR 0.80–1.39)}] in the normothermic group within 24 h. C_Cr was decreased on admission. Within 24 h C_Cr improved to normal values in normothermic patients [1.53 ml/s (IQR 1.15–2.35) {92 ml/min (IQR 69–141)}] and remained low in hypothermic patients [0.88 ml/s (IQR 0.63–1.38) {53 ml/min (IQR 38–83)}] (P=0.0006). No difference was found between the groups in the development of acute renal failure or the need for renal supportive therapy. Conclusion: Twenty four hours of MTH was associated with a delayed improvement in renal function. This was not reflected in the serum creatinine values, which were low in the hypothermic group. This transient impaired renal function appeared to be completely reversible within 4 weeks.     

Simultaneous analysis of MDR1 C3435T, G2677T/A, and C1236T genotypes by multiplexed mutagenically separated PCR.

P-glycoprotein (PGP) encoded by the multi-drug-resistance 1 (MDR1) gene is a member of the ATP-binding cassette (ABC) transporter family, drug-transporting proteins involved in the bioavailability and pharmacokinetics of various drugs. Several single nucleotide polymorphisms (SNPs) in the MDR1 gene have been identified so far that may influence PGP expression levels and function. Thus, genotyping for MDR1 polymorphisms and determining specific haplotypes may become an important tool in predicting individual susceptibility to developing drug resistance. We developed a new multiplexed allele-specific PCR method based on the principle of mutagenically separated PCR (MS-PCR) for rapid and reliable simultaneous genotyping of the C3435T polymorphism in exon 26 of the MDR1 gene and two additional SNPs (G2677T/A in exon 21 and C1236T in exon 12), which are in linkage disequilibrium with MDR1 C3435T. The accuracy and reliability of this method was confirmed by sequencing the respective regions in the MDR1 gene. This newly developed MDR1 MS-PCR will facilitate fast, accurate and economic analysis of MDR1 genotypes and will provide important information in optimizing individual therapeutic approaches.