Relationships of urinary adrenal steroids at age 8 years with birth weight, postnatal growth, blood pressure, and glucose metabolism

INTRODUCTION: Overactivity of the hypothalamic-pituitary-adrenal axis through a program set by early growth patterns is hypothesized to lead to central obesity, insulin resistance, and hypertension. We therefore examined links between adrenal steroid production and birth weight, rapid early growth, and body mass index (BMI), blood pressure, waist circumference, and resistance to insulin in early childhood through the action of adrenal steroids. METHODS: Timed overnight urine samples were collected in 461 children from a large representative birth cohort. In total 244 boys and 188 girls aged 8.2-8.4 yr completed the protocol. The excretion rates of individual steroids were measured to determine total androgen and cortisol metabolites. Indices of activity of 5alpha-androgen reduction of androgens and cortisol metabolites and 11beta-hydroxy steroid dehydrogenase activity were calculated. RESULTS: In both boys and girls, total urinary androgen and cortisol metabolites were positively related to current height, weight, BMI, and waist circumference. Girls had higher urine androgen metabolite levels and 5alpha-androgen indexes than boys, and in girls higher androgen metabolite excretion was associated with lower birth weight and faster postnatal weight gain. After adjustment for current BMI, total cortisol metabolites and 11beta-hydroxy steroid dehydrogenase index were not related to birth weight or postnatal weight gain in either sex. CONCLUSIONS: These data confirm early growth associations in this cohort seen with plasma levels of adrenal androgens at age 8 yr, at least in girls. Larger studies and follow-up during puberty are needed to exclude the possibility of programming of cortisol metabolism by early growth.     

Cardiovascular magnetic resonance characterization of peri-infarct zone remodeling following myocardial infarction

Background

Clinical studies implementing late gadolinium-enhanced (LGE) cardiovascular magnetic resonance (CMR) studies suggest that the peri-infarct zone (PIZ) contains a mixture of viable and non-viable myocytes, and is associated with greater susceptibility to ventricular tachycardia induction and adverse cardiac outcomes. However, CMR data assessing the temporal formation and functional remodeling characteristics of this complex region are limited. We intended to characterize early temporal changes in scar morphology and regional function in the PIZ.

Methods and results

CMR studies were performed at six time points up to 90 days after induction of myocardial infarction (MI) in eight minipigs with reperfused, anterior-septal infarcts. Custom signal density threshold algorithms, based on the remote myocardium, were applied to define the infarct core and PIZ region for each time point. After the initial post-MI edema subsided, the PIZ decreased by 54% from day 10 to day 90 (p = 0.04). The size of infarct scar expanded by 14% and thinned by 56% from day 3 to 12 weeks (p = 0.004 and p < 0.001, respectively). LVEDV increased from 34.7. ± 2.2 ml to 47.8 ± 3.0 ml (day3 and week12, respectively; p < 0.001). At 30 days post-MI, regional circumferential strain was increased between the infarct scar and the PIZ (-2.1 ± 0.6 and -6.8 ± 0.9, respectively;* p < 0.05).

Conclusions

The PIZ is dynamic and decreases in mass following reperfused MI. Tensile forces in the PIZ undergo changes following MI. Remodeling characteristics of the PIZ may provide mechanistic insights into the development of life-threatening arrhythmias and sudden cardiac death post-MI.     

Vertically Oriented Intramural Right Coronary Artery in Complete Transposition of the Great Arteries: Prospective Recognition and Surgical Implications

This report describes a rare case of complete transposition of the great arteries (TGA) with an intramural right coronary artery arising well above the sinotubular junction. Additionally in this case, the left circumflex artery arose anomalously as a branch from the right coronary. Identification of this anatomic anomaly was made by transthoracic echocardiography before surgery. The patient underwent a successful arterial switch operation on day 6 of life. Due to the preoperative diagnosis of the unusual right intramural coronary artery, the coronary transfer technique during the arterial switch was altered, allowing preservation of the right coronary artery.     

Self-esteem, confidence, and relationships in men treated with sildenafil citrate for erectile dysfunction

BACKGROUND: Men with erectile dysfunction (ED) often have low self-esteem, confidence, and sexual relationship satisfaction. OBJECTIVE: We evaluated the impact of sildenafil citrate and its generalizability across cultures on self-esteem, confidence, and sexual relationship satisfaction in men with ED using the Self-Esteem And Relationship (SEAR) questionnaire. DESIGN: Pooled analysis of 2 double-blind, placebo-controlled, flexible-dose trials of sildenafil with identical protocols: 1 was conducted in the United States and the other in Mexico, Brazil, Australia, and Japan. PATIENTS: Men > or = 18 years old with ED. MEASUREMENTS: The impact of treatment on psychosocial factors associated with ED was determined by patient responses to the SEAR questionnaire. Erectile function was determined using the International Index of Erectile Function (IIEF) and a global efficacy question. Successful sexual intercourse attempts were derived from event logs of sexual activity. Treatment effect sizes were calculated for all study outcomes. RESULTS: Compared with patients who received placebo (n = 274), patients who received sildenafil (n = 279) reported significantly greater improvements (P < .0001) in self-esteem, confidence, sexual relationship satisfaction, and in all sexual function domains of the IIEF. Treatment effect sizes were large (range, 0.7 to 1.2) for all SEAR components, and improvement in psychosocial measures showed moderate to high correlations (range, 0.50 to 0.83, P < .0001) with improvement in erectile function, percentage of successful intercourse attempts, and global efficacy. CONCLUSIONS: In men with ED from 5 different nations, sildenafil produced substantial improvements in self-esteem, confidence, and sexual relationship satisfaction. Improvements in these psychosocial factors were observed crossculturally and correlated significantly and tangibly with improvements in erectile function.     

Brain-Derived Neurotrophic Factor Modulates Auditory Function in the Hearing Cochlea

Neurotrophins prevent spiral ganglion neuron (SGN) degeneration in animal models of ototoxin-induced deafness and may be used in the future to improve the hearing of cochlear implant patients. It is increasingly common for patients with residual hearing to undergo cochlear implantation. However, the effect of neurotrophin treatment on acoustic hearing is not known. In this study, brain-derived neurotrophic factor (BDNF) was applied to the round window membrane of adult guinea pigs for 4 weeks using a cannula attached to a mini-osmotic pump. SGN survival was first assessed in ototoxically deafened guinea pigs to establish that the delivery method was effective. Increased survival of SGNs was observed in the basal and middle cochlear turns of deafened guinea pigs treated with BDNF, confirming that delivery to the cochlea was successful. The effects of BDNF treatment in animals with normal hearing were then assessed using distortion product otoacoustic emissions (DPOAEs), pure tone, and click-evoked auditory brainstem responses (ABRs). DPOAE assessment indicated a mild deficit of 5 dB SPL in treated and control groups at 1 and 4 weeks after cannula placement. In contrast, ABR evaluation showed that BDNF lowered thresholds at specific frequencies (8 and 16 kHz) after 1 and 4 weeks posttreatment when compared to the control cohort receiving Ringer’s solution. Longer treatment for 4 weeks not only widened the range of frequencies ameliorated from 2 to 32 kHz but also lowered the threshold by at least 28 dB SPL at frequencies ≥16 kHz. BDNF treatment for 4 weeks also increased the amplitude of the ABR response when compared to either the control cohort or prior to treatment. We show that BDNF applied to the round window reduces auditory thresholds and could potentially be used clinically to protect residual hearing following cochlear implantation.     

Reactivity of ambulatory blood pressure to physical activity varies with time of day

Blood pressure (BP) fluctuates over a 24-hour period, but it is unclear to what extent this variation is governed completely by changes in physical activity. Our aim was to use a BP "reactivity index" to investigate whether the BP response to a given level of physical activity changes during a normal sleep-wake cycle. Hypertensive patients (n=440) underwent simultaneous 24-hour ambulatory BP, heart rate (HR), and activity monitoring. BP and HR were measured every 20 minutes. Actigraphy data were averaged over the 15 minutes that preceded a BP measurement. Individual BP and HR reactivity indices were calculated using least-squares regression for twelve 2-hour periods. These indices were then analyzed for time-of-day differences using a general linear model. Systolic BP and HR were generally more reactive to physical activity than diastolic BP. The highest reactivity of systolic BP (mean+/-SE=4+/-1 mm Hg per logged unit change in activity) was observed between 8:00 AM and 10:00 AM (P=0.014). Between 10:00 AM and 12:00 PM, BP reactivity then decreased (P=0.048) and showed a secondary rise in the early afternoon. These 24-hour changes in BP reactivity did not differ significantly between groups formed on the basis of early and late wake times (P=0.485), medication use, age, and sex (P>0.350). In conclusion, under conditions of normal living, the reactivity of BP and HR to a given unit change in activity is highest in the morning and shows a secondary rise in the afternoon.     

Analysis of the clonal architecture of the human small intestinal epithelium establishes a common stem cell for all lineages and reveals a mechanism for the fixation and spread of mutations

Little is known about the clonal structure or stem cell architecture of the human small intestinal crypt/villus unit, or how mutations spread and become fixed. Using mitochondrial DNA (mtDNA) mutations as a marker of clonal expansion of stem cell progeny, we aimed to provide answers to these questions. Enzyme histochemistry (for cytochrome c oxidase and succinate dehydrogenase) was performed on frozen sections of normal human duodenum. Laser‐capture microdissected cells were taken from crypts/villi. The entire mitochondrial genome was amplified using a nested PCR protocol; sequencing identified mutations and immunohistochemistry demonstrated specific cell lineages. Cytochrome c oxidase‐deficient small bowel crypts were observed within all sections: negative crypts contained the same clonal mutation and all differentiated epithelial lineages were present, indicating a common stem cell origin. Mixed crypts were also detected, confirming the existence of multiple stem cells. We observed crypts where Paneth cells were positive but the rest of the crypt was deficient. We have demonstrated patches of deficient crypts that shared a common mutation, suggesting that they have divided by fission. We have shown that all cells within a small intestinal crypt are derived from one common stem cell. Partially‐mutated crypts revealed some novel features of Paneth cell biology, suggesting that either they are long‐lived or a committed Paneth cell‐specific long‐lived progenitor was present. We have demonstrated that mutations are fixed in the small bowel by fission and this has important implications for adenoma development. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Epidural morphine vs hydromorphone in post-Caesarean section patients

Purpose

The purpose of this randomized controlled double blind study was to compare the efficacy of pain relief and the side effects of epidural hydromorphone and morphine in postCaesarean patients.

Methods

In all patients, epidural anaesthesia was induced using carbonated lidocaine 2% with 1:200,000 epinephrine and 50μg fentanyl, given in incremental doses. Patients in Group 1 (n = 24) received 0.6 mg hydromorphone and patients in Group 2 (n = 22) received 3 mg morphine after delivery of the infant. Pain, pruritus and nausea were measured using a visual analog scale (at times: baseline, on admission to the recovery room, 3, 6, 12, 18 and 24 hr postoperatively), by the number of requests for additional medications and by an overall satisfaction score.

Results

There was no difference between the groups in pain relief or in the incidence and severity of side effects. Pruritus was more pronounced within the first six hours in Group 1 and at 18 hr in Group 2.

Conclusion

Hydromorphone provides no clinical benefit over epidural morphine for post operative analgesia following Caesarean section.