Cardiac specific ATP-sensitive K(+) channel (K(ATP)) overexpression results in embryonic lethality

Transgenic mice overexpressing SUR1 and gain of function Kir6.2[?N30, K185Q] K_ATP channel subunits, under cardiac α-myosin heavy chain (αMHC) promoter control, demonstrate arrhythmia susceptibility and premature death. Pregnant mice, crossed to carry double transgenic progeny, which harbor high levels of both overexpressed subunits, exhibit the most extreme phenotype and do not deliver any double transgenic pups. To explore the fetal lethality and embryonic phenotype that result from K_ATP overexpression, wild type (WT) and K_ATP overexpressing embryonic cardiomyocytes were isolated, cultured and voltage-clamped using whole cell and excised patch clamp techniques. Whole mount embryonic imaging, Hematoxylin and Eosin (H&;E) and α smooth muscle actin (αSMA) immunostaining were used to assess anatomy, histology and cardiac development in K_ATP overexpressing and WT embryos. Double transgenic embryos developed in utero heart failure and 100% embryonic lethality by 11.5 days post conception (dpc). K_ATP currents were detectable in both WT and K_ATP-overexpressing embryonic cardiomyocytes, starting at early stages of cardiac development (9.5 dpc). In contrast to adult cardiomyocytes, WT and K_ATP-overexpressing embryonic cardiomyocytes exhibit basal and spontaneous K_ATP current, implying that these channels may be open and active under physiological conditions. At 9.5 dpc, live double transgenic embryos demonstrated normal looping pattern, although all cardiac structures were collapsed, probably representing failed, non-contractile chambers. In conclusion, K_ATP channels are present and active in embryonic myocytes, and overexpression causes in utero heart failure and results in embryonic lethality. These results suggest that the K_ATP channel may have an important physiological role during early cardiac development.     

ST segment elevation typical for Brugada syndrome after intracoronary acetylocholine injection with retrosternal pain in history

Chest pain is mainly linked with acute coronary syndrome, but sometimes it can be the only manifestation of ventricular tachycardia. We present a case of a young man who was diagnosed with Brugada syndrome after intracoronary acetylocholine injection, with negative test with flecanaide. First manifestation of a disease was a chest pain.     

Supplementation with hydrocortisone on the 3rd-5th day following dexamethasone premedicated chemotherapy eliminated severe dizziness and postural hypotension

We present the case of a 60 year-old woman with a stage III fallopian tube cancer submitted to hysterectomy and bilateral salpingo-oophorectomy with partial omenectomy, followed by six courses of chemotherapy and revision surgery. After each course of chemotherapy (paclitaxel + carboplatin) preceded by premedication with dexamethasone, she suffered from side- -effects, of which the most unpleasant was severe dizziness appearing on the third, fourth and fifth day following the listed combination of drugs. It was revealed that dizziness with concomitant sweating and rapid pulse, noted in the standing position, was combined with marked postural hypotension. Considering the possibility of a temporary pituitary-adrenal axis suppression caused by premedication with a very large dose of dexamethasone, during those three days she was supplemented with small doses of hydrocortisone, which caused almost complete disappearance of the mentioned symptoms. Our conclusion is that postural hypotension causing severe dizziness initially linked with chemotherapeutic drugs can be eliminated or markedly reduced by three days supplementation with hydrocortisone applied after the expected wash out of the dexamethasone.     

Right ventricular dysfunction and exercise capacity after inferior (posterior) wall acute myocardial infarction

Tissue Doppler echocardiography is a novel technique that can be used to diagnose right ventricular (RV) systolic dysfunction. Until recently, there have been no data on the influence of tissue Doppler-derived RV systolic dysfunction on exercise capacity after inferior (posterior) myocardial infarction (MI). We studied 90 consecutive patients (76% men, mean age 61 ± 10 years) with first inferior ST-segment elevation MI and left ventricular ejection fraction ≥45%. RV systolic dysfunction was defined as RV systolic myocardial velocity <11.5 cm/s at the basal segment of the RV free wall assessed by pulse tissue Doppler. Patients were categorized as with or without RV systolic dysfunction (RV systolic myocardial velocity 9.34 ± 1.36 and 13.74 ± 1.58 cm/s, respectively). A cardiopulmonary exercise test was performed before or soon after discharge (day 14 ± 10). Patients with RV systolic dysfunction had lower oxygen consumption assessed as percent predicted oxygen uptake in liters per minute and milliliters per kilogram per minute at their anaerobic threshold (61 ± 11% vs 69 ± 17%, p = 0.007; 53 ± 12% vs 61 ± 19%, p = 0.012, respectively) and at peak exercise (71 ± 12% vs 83 ± 16%, p = 0.0001; 62 ± 14% vs 74 ± 21%, p = 0.002, respectively). Multivariate regression analysis revealed that the following independent factors negatively influenced exercise capacity: RV systolic dysfunction, female gender, age, lower body mass index, current smoking, and maximal troponin I concentration. In conclusion, we found decreased exercise capacity in patients with systolic RV dysfunction assessed by pulse tissue Doppler in patients with inferior (posterior) wall acute MI despite preserved left ventricular function.     

Comprehensive investigation of genetic variation in the 8q24 region and multiple myeloma risk in the IMMEnSE consortium

Genome-wide association studies (GWAS) have shown that the 8q24 region harbours multiple independent cancer susceptibility loci, even though it is devoid of genes. Given that no GWAS data are currently available for multiple myeloma (MM), we tested the hypothesis that genetic variants in this region could play a role in MM risk. We genotyped 20 single nucleotide polymorphisms of 8q24 in 1188 MM cases and 2465 controls and found a statistically significant (P = 0·0022) association between rs2456449 and MM risk. These data provide further evidence that the genetic variability in the 8q24 region is associated with cancer risk, particularly haematological malignancies.