Effects of transient myocardial ischemia on the ventricular defibrillation threshold

BACKGROUND: Acute myocardial ischemia and the mode of ventricular fibrillation (VF) induction influence the ventricular defibrillation threshold (DFT). OBJECTIVES: The purpose of this study was to determine the effects of transient regional left ventricular (LV) ischemia on the DFT. METHODS: Ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT), and DFT were measured under nonischemic conditions (control) in 26 pigs weighing 25-35 kg. Myocardial ischemia was then induced by occlusion of the mid left anterior descending coronary artery, and measurements of ERP and VFT were repeated after 2 minutes of occlusion. The coronary artery ligation was released immediately after the onset of VF and DFT was measured. RESULTS: LV ERP was unchanged by ischemia (199 +/- 19 ms at control vs. 200 +/- 22 ms under ischemic conditions, P = 0.799), whereas VFT was significantly lower during coronary occlusion (10.7 +/- 5.4 mA vs. 37.7 +/- 13 mA, P = 0.000). Brief myocardial ischemia caused a significant increase in DFT (13.5 +/- 12.6 J after coronary occlusion vs. 6.8 +/- 6.8 J at control, P = 0.023). The duration of coronary occlusion was not correlated with the amounts of energy required to defibrillate (P = 0.526). CONCLUSIONS: This experimental study shows that transient myocardial ischemia markedly increases the DFT, suggesting that specific defibrillation algorithms should be designed for recipients of implantable defibrillators at risk of myocardial ischemia.     

Metabolic syndrome risk factors and estimated glomerular filtration rate among children and adolescents

The aim of this study was to seek the possible relationship between estimated glomerular filtration rate (e-GFR) and anthropometric indexes, lipids, insulin sensitivity, and metabolic syndrome risk factors among healthy children and adolescents. Sufficient evidence suggest that obesity is related with a novel form of glomerulopathy named obesity-related glomerulopathy (ORG) among adults, children, and adolescents. Glomerular filtration rate was estimated from serum creatinine in 166 healthy children and adolescents [79 males, 87 females; age 10.6 ± 3.3 (3–18) years]. Anthropometric indexes and systolic and diastolic blood pressure were measured. Fasting insulin, glucose, creatinine, uric acid, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglycerides were estimated. Insulin sensitivity was estimated from known formulas. The presence of certain metabolic syndrome risk factors was checked among the studied population. Boys showed higher e-GFR rates than girls (f = 8.49, p = 0.004). We found a strong positive correlation between e-GFR and body weight (r = 0.415), body mass index (BMI) (r = 0.28), waist circumference (r = 0.419), hip circumference (r = 0.364), birth weight (r = 0.164), systolic blood pressure (SBP) (r = 0.305), and mean arterial pressure (MAP) (r = 0.207). A negative correlation was found between e-GFR and fasting glucose (r = -0.19), total cholesterol (r = -0.27) and LDL-cholesterol (r = -0.26). Clustering of metabolic syndrome risk factors among certain individuals was correlated with higher e-GFR rates (f = 3.606, p = 0.007). The results of this study suggest that gender, anthropometric indexes, and SBP are strong positive determinants of e-GFR among children and adolescents. Waist circumference is the most powerful determinant of e-GFR. Fasting glucose and lipid abnormalities are negative determinants of e-GFR among the studied population. Clustering of metabolic syndrome risk factors is coupled with higher e-GFR rates.     

HLA-B*5701 frequency n Chilean HIV-infected patients and in general population

It has been demonstrated that HLA-B*5701 screening reduces the risk for hypersensitivity reaction to abacavir in HIV-infected patients. Since B*5701 prevalence varies among different populations, it is important to determine the carrier frequency prior to its use for the screening of HIV-infected patients. The aim of this study was to determine HLA-B*5701 carrier frequency in Chilean general population and HIV-infected patients referred for B*5701 typing. For that purpose 300 blood bank donors and 492 abacavir-naïve HIV-infected patients from Chile were screened for B*5701 by a sequence specific primer PCR. We detected 14/300 (4.7%) B*57-positive individuals in the Chilean general population, 11 (3.7%) were B*5701 positive, and 3 (1%) had another subtype. All were heterozygous, thus a B*5701 allele frequency of 2% was determined. Eleven of 492 (2.2%) HIV-patients carried a B*5701 allele. The difference between these frequencies is probably due to slow progression of HIV infection in HLA-B*5701 carriers, thus less patients would require antiretroviral therapy and B*5701 typing. Considering the usefulness of B*5701 screening, its prevalence in the Chilean general population, and the availability of a validated method, we conclude that HLA-B*5701 typing in Chilean HIV-infected patients about to initiate abacavir treatment is strongly recommended.     

Agenesis of the corpus callosum associated with narcolepsy-cataplexy

We describe a 24-year-old man with episodes of intense desire to sleep for periods ranging from 2min to 3h, episodes of generalized weakness and inability to speak without alteration of consciousness, frequent hypnagogic hallucinations during sleep and occasionally transient paralysis of limbs upon awakening. Brain MRI demonstrated elevation of the third ventricle, a characteristic lack of depiction of the corpus callosum and extension of the bihemispheric fissure to the third ventricle. We assume that structural changes of the base of frontal lobes, diencephalon and brainstem, can be accountable for symptomatic narcolepsy and cataplexy.     

Kaposi's sarcoma-associated herpesvirus-encoded interleukin-6 and G-protein-coupled receptor regulate angiopoietin-2 expression in lymphatic endothelial cells

Kaposi's sarcoma (KS) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and consists of proliferating spindle cells, which are related to lymphatic endothelial cells (LEC). Angiopoietin-2 (Ang2) is a secreted proangiogenic and lymphangiogenic molecule. Here, we show the expression of Ang2 protein in KS and confirm that KSHV infection up-regulates Ang2 in LEC. We show that a paracrine mechanism contributes to this up-regulation. A lentiviral library of individual KSHV-encoding genes, comprising the majority of known latent genes and a selection of lytic viral genes, was constructed to investigate the underlying mechanism of this up-regulation. Two lytic genes, viral interleukin-6 (vIL6) and viral G-protein-coupled receptor (vGPCR), up-regulated Ang2 expression in LEC. Both vIL6 and vGPCR are expressed in KSHV-infected LEC and caused up-regulation of Ang2 in a paracrine manner. KSHV, vIL6, and vGPCR up-regulated Ang2 through the mitogen-activated protein kinase (MAPK) pathway. Gene expression microarray analysis identified several other angiogenic molecules affected by KSHV, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis, which is also affected by vIL6 and vGPCR in LEC, and matrix metalloproteinases, which could act in concert with Ang2 to contribute to KS development. These findings support the paracrine and autocrine roles of the lytic KSHV-encoded proteins, vIL6 and vGPCR, in KS pathogenesis and identify Ang2 as a potential therapeutic target for this neoplasm.     

Endocrinology: Follicle cyst formation after administration of different gonadotrophin-releasing hormone analogues for assisted reproduction

The aim of this study was to examine the occurence of ovariancysts during the administration of three different gonadotrophin-releasinghormone analogues (GnRHa) in the long protocol as well as theircharacteristics, management and outcome compared with patientswith no cyst formation. A total of 172 in-vitro fertilization(IVF) cycles in which GnRHa was administered at menstruationwere analysed. Group B consisted of 72 cycles in which buserelinwas used. Of these, 10 (13.9%) were with cysts (group B1) and62 (86.1%) without cysts (group B2). Group T included 49 cyclesin which triptorelin was injected. Of these, seven (14.2%) werewith cysts (group T1) and 42 (85.7%) without cysts (group T2).Group L comprised 51 cycles in which leuprolide was administered.Of these, eight (15.7%) were with cysts (group L1) and 43 (84.3%)without cysts (group L2). All women with ovarian cysts had higherserum oestradiol concentrations and all except five underwentcyst aspiration with no complication. No differences were observedin the number of follicles and oocytes between groups B, T andL or between the groups with cysts and those without cysts.The pregnancy rate was similar in all groups. In conclusion,follicle cyst formation does not seem to be related to the useof a specific GnRHa, its short- or long-acting form or to themode of administration. In addition, follicle cyst aspirationis a safe and successful solution to the problem of functionallyactive ovarian cysts.     

Tumor cell proliferation in early gastric cancer: biological and clinical behavior

BACKGROUND/AIMS: Recently, early gastric cancers without lymph node metastasis have successfully been removed through a simple endoscopic resection. Tumor cell proliferation may be related to the malignant potential of early gastric cancer. The purpose of this study is to prospectively investigate the relationship between the incorporation rate of bromodeoxyuridine (BrdU) into the DNA of dividing cells, and the main biological and clinical early gastric cancer characteristics. METHODOLOGY: Multiple tumor specimens were taken from 27 early gastric cancers and analyzed through anti-BrdU monoclonal antibody. Tumor BrdU labeling index (LI=% positive cells over 2,000 tumor cells) was determined. Early gastric cancers were evaluated in tumor size, mucosal and submucosal involvement, histologic type and grading, lymphatic and venous invasion, and nodal metastasis. RESULTS: BrdU LI was significantly higher in patients with submucosal neoplastic invasion, Pen A Kodama type, tumor vessel invasion and lymph node involvement. Early gastric cancer patients with over 22% BrdU LI showed a significantly higher incidence of submucosal invasion, lymphatic-venous involvement and a reduced survival when compared to patients with medium (12-22%) or low BrdU LI (<12%). CONCLUSIONS: Our results suggest that BrdU LI may be considered a useful indicator of early gastric cancer aggressiveness.