Differences in the activation patterns between sustained and self-terminating episodes of human ventricular fibrillation

BACKGROUND. Experimental studies have suggested that R-R interval dynamics during ventricular fibrillation (VF) have organized features, but whether dynamic behavior of non-sustained VF differs from sustained VF is unknown. AIM. The purpose of this study was to investigate whether the dynamics of R-R intervals during non-sustained VF differs from the dynamics during sustained VF. METHODS. A group of 67 patients undergoing routine implantable cardioverter defibrillator (ICD) testing was studied. Forty-three VF events containing mean of 38 local cardiac activation intervals before the termination by ICD shock were analyzed. From intracardiac electrogram recordings, the ratio between the short and long term variability (SD1/SD2) and fractal scaling exponent ( &#102 ) were analyzed. After the initial analyses, data sets were randomized and reanalyzed. Local activation dynamics were then also compared in seven patients with both sustained and spontaneously terminating VF episodes. RESULTS. Randomization caused a change in the VF dynamics from organized toward less organized dynamics ( &#102 ) from 1.08 &#45 0.57 to 0.81 &#45 0.45, P < 0.05 and SD1/SD2 from 0.80 &#45 0.23 to 1.04 &#45 0.20, P < 0.01). Spontaneously terminating VF showed more organized dynamics than sustained VF terminated by shock (P < 0.05). CONCLUSIONS. Local cardiac activation dynamics during initial phase of human VF shows organized dynamics. Spontaneously terminating VF episodes have more structured dynamics than sustained VF. Thus, the dynamic behavior of local cardiac activation intervals may be related to the maintenance of ventricular tachyarrhythmias.     

A realist account of the ontology of impairment

This paper provides a philosophical analysis of the ontology of impairment, in part social and in part not. The analysis is based on the division between two categories of facts concerning the world we live in: "brute" and institutional facts. Brute facts are those that require no human institution for their existence. To state a brute fact requires naturally the institution of language, but the fact stated is not the same as the statement of it. For example, regardless of any human institution or opinion, the presence of an extra chromosome 21 is a brute fact, and despite of people's constructions or deconstructions, this fact remains. As for the lives of people with extra chromosome 21, the social reality and human institutions enter the picture. The social and moral status of these people is never a matter of brute fact.     

A mouse model for Stickler's syndrome: ocular phenotype of mice carrying a targeted heterozygous inactivation of type II (pro)collagen gene (Col2a1)

The influences of targeted heterozygous inactivation of type II (pro)collagen gene (Col2a1) on eye structures in the 15-month-old C57BL/6JOlaHsd mouse was studied. The eyes were collected from C57BL mice heterozygous for a targeted inactivation of one allele of the Col2a1 gene (Col2a1(+/-) mice). The eyes of C57BL mice with normal gene alleles were used as controls (Col2a1(+/+) mice). Ocular histology was analyzed from tissue sections, stained with hematoxylin and eosin, toluidine blue and alcian blue. Type II collagen was localized by immunohistochemistry. Hyaluronan (HA) was stained utilizing the biotinylated complex of the hyaluronan-binding region of aggrecan and link protein (bHABC). The anterior segment of the eye was well-formed in both genotypes, but typical folding of ciliary processes was decreased, while increased stromal extracellular matrix vacuolization was seen in the Col2a1(+/-) mice. In the lens of these mice, subcapsular extracellular matrix changes were observed. Differences in retinal structures or the number of the eyes with retinal detachment were not detected between the genotypes. In Col2a1(+/-) mice, staining for type II collagen was weaker in cornea, ciliary body, iris, lens, vitreous, retina, choroid and sclera than in the control mice. HA staining was detected in the extraocular tissues, ciliary body, iris and the choroid of both genotypes. HA staining was observed only in the vitreous body of the control animals. Heterozygous inactivation of Col2a1 gene causes structural defects in the murine eye. The observed structural changes in the ciliary body, lens and vitreous of the Col2a1(+/-) mice may represent ocular features found in the human Stickler syndrome, where the abnormalities result from COL2A1 gene mutations which lead to functional haploinsufficiency.     

Oral contraceptive use before first birth and risk of breast cancer: a case control study

Background  

Our investigation sought to compare changes in sexual function following supracervical hysterectomy (SCH) and total abdominal hysterectomy (TAH).     

Effects of carriers and storage of formulation on the lung deposition of a hydrophobic and hydrophilic drug from a DPI

The effects of carriers, the drug:carrier ratio and a 1 month storage period of a formulation in permeable polystyrene tube at 40 degrees C/75% RH on the in vitro pulmonary deposition of model drugs from dry powder inhaler (DPI) were evaluated. Budesonide (hydrophobic) and salbutamol sulphate (hydrophilic) were used as model drugs. Mannitol and glucose were used as the carriers. In addition, lactose 110M was used as the carrier for budesonide. The novel multiple dose Taifun was used as a DPI; Taifun is a breath-actuated inhaler that contains the powder formulation in a reservoir chamber. The respirable fractions (RF%) values of the drugs were determined by the "Andersen" sampler. The RF% values of salbutamol sulphate increased with an increase in the drug:carrier ratio before storage, whereas the drug:carrier ratio did not affect the RF% values after storage. In the case of budesonide, the drug:carrier ratio did not affect the RF% values before storage, instead the RF% values of budesonide increased with an increase in the drug:carrier ratio after storage. The RF% values of salbutamol sulphate decreased after storage of the formulation, this was not dependent on the carrier and the drug:carrier ratio. However, with budesonide the effect of the storage on its RF% values was dependent on which carrier was used and also the drug:carrier ratio. Overall, storage had less effect on the RF% values of budesonide than those of salbutamol sulphate. The highest RF% values of budesonide were obtained when mannitol was used as the carrier. Furthermore, the RF% values of salbutamol sulphate tended to be higher when mannitol was used as the carrier instead of glucose.     

Human pHyde is not a classical tumor suppressor gene in prostate cancer

A novel putative tumor suppressor gene, pHyde, was recently cloned from rat prostate. The rat gene has been shown to inhibit prostate cancer cell proliferation both in vitro and in vivo. However, the role of human pHyde in prostate cancer has not been studied before. Here, we analyzed human prostate cancer cell lines (LNCaP, DU145, PC-3, 22Rv1), xenografts (LuCaP 23.1, 35, 41, 49, 58, 69, 70 and 73) and clinical prostate carcinomas for genetic alterations and expression of pHyde. The expression of pHyde in normal human tissues as well as in prostate cancer was studied by Northern analysis and real-time quantitative RT-PCR. It was ubiquitously expressed in all normal tissues analyzed. Although, the expression was significantly (p=0.007) lower in poorly differentiated than in well and moderately differentiated carcinomas, there were no differences in the expression levels between benign prostate hyperplasia, untreated primary and recurrent hormone-refractory prostate carcinomas (p=0.607). Altogether, missense mutations were detected in 2 out of 68 samples studied ( approximately 3%) by denaturing high-performance liquid chromatography (DHPLC) and sequencing. One of the samples with the mutation also exhibited a loss of a gene copy by fluorescence in situ hybridization (FISH). This was the only sample that exhibited a genetic alteration in both alleles, suggesting that the human pHyde is not a classical prostate tumor suppressor gene. The reduced expression of the gene found in some tumors warrant further studies.     

Myocardial perfusion,oxidative metabolism,and free fatty acid uptake in patients with hypertrophic cardiomyopathy attributable to the Asp 175Asn mutation in the α-tropomyosin gene: A positron emission tomography study

Background  The relationship between myocardial metabolic changes and the severity of left ventricular (LV) hypertrophy in patients with hypertrophic cardiomyopathy (HCM) is largely unknown. We characterized metabolic abnormalities in patients with a genetically identical cause for HCM but with variable LV hypertrophy. Methods and Results  Eight patients with HCM attributable to the Asp175Asn mutation in the α-tropomyosin gene underwent myocardial perfusion, oxidative, and free fatty acid (FFA) metabolism measurements via positron emission tomography and oxygen 15-labeled water, carbon 11 acetate, and fluorine 14(R,S)-[18F] Fluoro-6-thia-heptadecanoic acid (18 FTHA). LV mass, work, and efficiency were assessed by echocardiography. Thirty-six healthy volunteers served as control subjects. Compared with control subjects, HCM patients had increased myocardial oxidative metabolism and FFA uptake (P<.05). However, in patients, LV mass was inversely related to global myocardial perfusion, oxidative metabolism, and FFA uptake (all P<.03), and regional wall thickness was inversely related to regional perfusion (P<.01), oxidative metabolism (P<.001), and FFA uptake (P<.01). Therefore patients with mild (LV mass less than median of 177 g) but not advanced LV hypertrophy were characterized by increased perfusion, oxidative metablism, and LV efficiency as compared with control subjects (P<.05). Conclusions  In HCM attributable to the Asp 175Asn mutation in the α-tropomyosin gene, myocardial oxidative metabolism and FFA metabolism are increased and inversely related to LV hypertrophy at both the whole heart and regional level. Increased metabolism and efficiency characterize patients with mild myocardial hypertrophy. These hypermetabolic alterations regress with advanced hypertrophy. Dis Tuunanen and Kuusisto contributed equally to this work This study was financially supported by an EVO grant (Kuopio University Hospital), as well as the Turunen Foundation, Instrumentarium Foundation, and Finish Cultural Foundation.     

18F-FDG assessment of glucose disposal and production rates during fasting and insulin stimulation: a validation study.

The glucose analog (18)F-FDG is commonly used to quantify regional glucose uptake in vivo. The aim of this study was to test whether the analysis of plasma (18)F-FDG kinetics could be used to estimate endogenous glucose production (EGP) and the total rate of appearance (Ra), total rate of disappearance (Rd), and the metabolic clearance rate (MCR) of glucose. METHODS: Fourteen pigs were coinjected with (18)F-FDG and 6,6-(2)H-glucose ((2)H-G) during fasting (n = 6) and during physiologic (1.0 mU.kg(-1).min(-1), n = 4) and supraphysiologic (5.0 mU.kg(-1).min(-1), n = 4) euglycemic hyperinsulinemia. Arterial plasma was sampled for 180 min to quantify the parameters for the 2 tracers. RESULTS: Fasting Rd((2))(H-G) and Rd(FDG) were 12.3 +/- 2.1 and 13.3 +/- 1.3 micromol.kg(-1).min(-1) (difference not statistically significant [NS]). M values were more than doubled between the 2 clamp studies (P < 0.0001). Rd((2))(H-G) and Rd(FDG) were dose-dependently higher during the hyperinsulinemic state (19.8 +/- 3.7 vs. 18.9 +/- 1.1 and 31.4 +/- 4.1 vs. 31.9 +/- 2.3 in 1.0 and 5.0 mU.kg(-1).min(-1) studies, respectively; difference between tracers NS) than during the fasting state, with a parallel suppression of EGP((2))(H-G) and EGP(FDG). Parameters estimated by (18)F-FDG and (2)H-G were equivalent in all groups; their agreement was confirmed by Bland-Altman examination. Total Rd(FDG) correlated with Rd((2))(H-G) (r = 0.74; P = 0.003), M (r = 0.92; P = 0.001), MCR((2))(H-G) (r = 0.52; P = 0.037), and EGP((2))(H-G) (r = -0.71; P = 0.004). EGP(FDG) correlated with EGP((2))(H-G) (r = 0.62; P = 0.018), Rd((2))(H-G) (r = -0.78; P = 0.001), and MCR((2))(H-G) (r = -0.67; P = 0.008). The (18)F-FDG mean transit time correlated inversely with the M and Rd values and positively with EGP. CONCLUSION: The glucose analog (18)F-FDG can be used in the simultaneous estimation of whole-body glucose turnover and production and regional (18)F-FDG PET measurements under both fasting and insulin-stimulated conditions.