Arrhythmias in transposition of the great arteries after the Mustard operation

Disorders of rhythm or conduction in patients with transposition of the great arteries (TGA) after the Mustard operation have been widely reported. This study provides a systematic evaluation of the electrophysiologic function of 87 survivors of the Mustard operation at a single institution. Surface electrocardiograms were reviewed in all 87 patients, Holter monitoring data in 26 patients, exercise electrocardiograms in 21 patients, and invasive electrophysiologic data in 61 patients. Surface electrocardiograms showed normal sinus rhythm in 52%, sinus node dysfunction in 27%, and atrioventricular block in 16%. Holter monitoring was obtained in an unselected subgroup of 26 patients who had a mean age of 12 years and a mean interval from operation of 9 years. Sinus node dysfunction was found in 58%, atrioventricular block in 27% ventricular ectopy in 50%, supraventricular ectopy in 27%, and no abnormalities in only 8%. Intracardiac electrophysiologic evaluation showed a high frequency of abnormal sinus node recovery times and suboptimal response of the atrioventricular-conduction system to rapid atrial pacing. When all modalities used in this study were considered, sinus node dysfunction occurred in 47%, ectopy in 34% and atrioventricular block in 23%. Although only 30% of patients had no evidence of arrhythmia, symptoms of rhythm or conduction disturbances were rare.     

CO uptake kinetics of red cells and CO diffusing capacity.

The rate at which CO displaces oxygen from combination with hemoglobin in intact red cells was measured spectrophotometrically in whole blood thin films that minimize unstirred layer extra-cellular diffusion barriers. A step-change was made in CO tension from zero to one of four values (2, 7, 21 and 70 Torr) during a constant background of one of eight O2 tensions (0, 40, 70, 100, 153, 214, 285 and 428 Torr). For PO2 greater than 100 Torr measured red cell initial CO uptake rates were compared with calculated rates at the same PCO-PO2 based on the Gibson-Roughton rate equation (Gibson and Roughton, Proc. R. Soc. B 143: 310-334, 1955) for a well mixed Hb solution. Measured CO uptake rates expressed as initial rate of saturation change (delta S/delta t) quantitatively followed the theoretical rate equation (time in seconds) [sequence: see text] These measurements provide new values for theta CO, the specific conductance of whole blood (ml.min-1.Torr-1; PCO, PO2 in Torr): [sequence: see text] These results signify that in vivo, in normoxia and hyperoxia, red cell CO uptake rate is wholly reaction rate limited and that pulmonary capillary red cell CO diffusion equilibrium is rapidly achieved. The Bohr-Krogh assumption that red cell PCO = 0 during CO uptake is untrue.     

Effects of the calcineurin dependent signaling pathway inhibition by cyclosporin A on early and late cardiac remodeling following myocardial infarction

BACKGROUND: The calcineurin-mediated signaling pathway has been implicated as one of the crucial pathways in cardiac hypertrophy. However, the role of calcineurin pathway on cardiac remodeling after myocardial infarction (MI) has not been well defined. METHODS: Infarcted rats (n = 45) were randomized into calcineurin inhibitor, cyclosporin A (CsA) or vehicle groups, 3 days after MI and treated for 2 weeks (early post-MI cardiac remodeling stage), or randomized 17 days after MI and treated for 2 weeks (late remodeling stage). RESULTS: Calcineurin pathway inhibition during the early cardiac remodeling stage attenuated the myocardial hypertrophy after MI (P < 0.05). However, left ventricular dimensions were further increased and fractional shortening deteriorated with calcineurin inhibition during this stage (P < 0.05, each). During late remodeling stage, CsA treatment did not affect myocardial hypertrophy and cardiac dilation following MI. CONCLUSION: Our results strongly support the hypothesis that calcineurin pathway mediates compensatory myocardial hypertrophy during the early remodeling stage after MI. However, the calcineurin pathway does not seem to affect the late remodeling after MI.     

Patterns of anismus and the relation to biofeedback therapy

PURPOSE: A study was undertaken to assess physiologic characteristics and clinical significance of anismus. Specifically, we sought to assess patterns of anismus and the relation of these findings to the success of therapy. METHODS: Sixty-eight patients were found to have anismus based on history and diagnostic criteria including anismus by defecography and at least one of three additional tests: anorectal manometry, electromyography, or colonic transit time study. Interpretation of defecography was based on the consensus of at least three of four observers. Anal canal hypertonia (n=32) was defined when mean and maximum resting pressures were at least 1 standard deviation higher than those in 63 controls. There were two distinct defecographic patterns of anismus: Type A (n=26), a flattened anorectal angle without definitive puborectalis indentation but a closed anal canal; Type B (n=42), a clear puborectalis indentation, narrow anorectal angle, and closed anal canal. Outcomes of 57 patients who had electromyographybased biofeedback therapy were reported as either improved or unimproved at a mean follow-up of 23.7 (range, 6–62) months. These two types of anismus were compared with biofeedback outcome to assess clinical relevance. RESULTS: Patients with Type A anismus showed greater perineal descent at rest (mean, 5.1 vs. 3.5 cm;P < 0.01), greater dynamic descent between rest and evacuation (mean, 2.7 vs. 1.4 cm;P <0.01), greater difference of anorectal angle between rest and evacuation (mean, 14.6 vs. ?3.1°;P <0.001), higher mean resting pressure (mean, 77.1 vs. 62.8 mmHg;P <0.05), lower mean squeeze pressure (58.8 vs. 80.7 mmHg;P <0.05), and a higher incidence of anal canal hypertonia (69.2 vs. 33.3 percent;P <0.01) than did patients with Type B anismus. Only 25 percent of patients who had Type A anismus with anal canal hypertonia were improved by biofeedback therapy. Conversely, 86 percent of patients with Type B anismus without anal canal hypertonia were successfully treated with biofeedback (P <0.001; Fisher's exact test). CONCLUSIONS: These two distinct physiologic patterns of anismus correlate with the success of biofeedback treatment. Therefore, knowledge of these patterns may help direct therapy.     

Prevalence of the Brugada-type ECG recorded from higher intercostal spaces in healthy Korean males.

BACKGROUND: Electrocardiograms (ECGs) recorded from the higher intercostal spaces (ICSs) are reported to be helpful for the diagnosis of Brugada syndrome (BS). However, the prevalence of Brugada-type ECG changes recorded from the higher ICSs is unknown in the healthy Korean population. METHODS AND RESULTS: A total of 225 healthy Korean male subjects with a mean age of 44+/-13 (20-69) years with no syncope or family history of sudden death were enrolled in the present study. ECGs were taken from 4th, 3rd, and 2nd ICSs and examined for Brugada-type ECG changes. There were none on the routine 12-lead ECGs, but 3 (1.3%) of the 225 subjects had a Brugada-type ECG recorded from the higher ICSs and 1 of them had a Brugada-type ECG recorded at both the 2nd and 3rd ICSs. The prevalence of the Brugada-type ECG was 1.3% at the 3rd ICS, 0.4% at the 2nd ICS. All were type 2. CONCLUSION: Some healthy Korean males with normal routine ECGs show Brugada-type 2 changes on ECGs recorded from higher ICSs.     

Identification and characterization of a reptilian GnRH receptor from the leopard gecko

Gonadotropin-releasing hormone (GnRH) plays a pivotal role in the regulation of reproductive functions through interactions with its specific receptor. We describe the first molecular cloning and characterization of a full-length GnRH receptor (GnRHR) from the leopard gecko Eublepharis macularius. It has a distinct genomic structure consisting of five exons and four introns, compared with all the other reported GnRHR genes. A native GnRH form, cGnRH-II, stimulated inositol phosphate (IP) production in COS-7 cells transiently transfected with the GnRHR, in a dose dependent manner. The mRNA was expressed in all the tissues and organs examined. Molecular phylogenetic analysis revealed that the cloned GnRHR belongs to the type 2/nonmammalian I GnRHR. Low-expression levels were observed from the pituitary glands of reproductively active leopard geckos, indicating the possibility that there is at least one more type of GnRHR highly expressed in the pituitary gland for the gonadotropin secretion in this reptile.     

The activation of aging stereotypes in younger and older adults

The activation of ageism and aging stereotypes in younger and older adults was investigated by manipulating both the valence and the stereotypicality of trait stimuli. Participants completed a lexical decision task in which the stimulus onset asynchronies (SOAs) between the prime and target stimuli were varied to examine the effects of automatic and controlled processing (300 and 2,000 ms, respectively). Both younger and older adults demonstrated strong stereotype activation for elderly stereotypes but relatively weak activation for young stereotypes. Both younger and older adults also demonstrated a positive bias toward older people, which was not moderated by SOA. These findings suggest that younger and older adults do not differ in their accessibility to aging stereotypes or to their age-based biases, which appear to be positive toward elderly people.     

Efficacy and safety of combination therapy with SGLT2 and DPP4 inhibitors in the treatment of type 2 diabetes: A systematic review and meta-analysis

Background

This review evaluated the efficacy and safety of a combination therapy comprising a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) in type 2 diabetes.