Attenuation of diabetic hyperphagia in neuropeptide Y--deficient mice

The combined effects of increased hypothalamic signaling by neuropeptide Y (NPY) and decreased signaling by melanocortins are hypothesized to stimulate food intake when body fat stores are depleted. To investigate NPY's role in the hyperphagic response to uncontrolled diabetes, streptozotocin (STZ) (200 mg/kg intraperitoneally) or saline vehicle was given to NPY-deficient (Npy(--/--)) and wild-type (Npy(+/+)) mice. In Npy(+/+) mice, STZ-induced diabetes increased mean daily food intake to plateau values 50% above baseline intake (+2.0 +/- 0.6 g/day; P < or = 0.05), an effect that was not seen in STZ-treated Npy(--/--) mice (+0.8 +/- 0.1 g/day; NS), despite comparably elevated levels of plasma glucose and comparably decreased levels of body weight, fat content, and plasma leptin. Unlike the impaired feeding response to uncontrolled diabetes, Npy(--/--) mice exhibit intact hyperphagic responses to fasting (Erickson et al. [1], Nature 381:415-418, 1996). To investigate whether differences in hypothalamic melanocortin signaling can explain this discrepancy, we used in situ hybridization to compare the effects of STZ-diabetes and fasting on pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) mRNA levels in the hypothalamic arcuate nucleus (ARC) of Npy(--/--) and Npy(+/+) mice. AgRP mRNA levels were increased by both fasting and STZ-diabetes, but the increase in STZ-diabetes was small (50-80%) compared with the effect of fasting (approximately 20-fold increase of AgRP mRNA). STZ-diabetes also lowered POMC mRNA levels by 65% in the ARC of Npy(+/+) mice (P less-than-or-equal 0.05) but by only 11% in Npy(--/--) mice (NS); fasting significantly lowered POMC mRNA levels in both genotypes. We conclude that NPY is required for both the increase of food intake and the decrease of hypothalamic POMC gene expression induced by uncontrolled diabetes. In contrast, NPY is not required for either of these responses when the stimulus is food deprivation. Moreover, fasting is a more potent stimulus to hypothalamic AgRP gene expression than is STZ-diabetes. Therefore, central nervous system melanocortin signaling appears to be suppressed more effectively by fasting than by uncontrolled diabetes, which provides a plausible explanation for differences in the feeding response to these two stimuli in mice lacking NPY.     

Ideal culture time for improvement in sperm motility from testicular sperm aspirates of men with azoospermia

PURPOSE: The motility of testicular derived spermatozoa reflects viability and predicts success during intracytoplasmic sperm injection. Although improvements in sperm motility are seen after incubation for extended periods, no guidelines suggest duration or media use for optimal improvement in motility. MATERIALS AND METHODS: Between July 1999 and February 2005 testicular aspirations were performed on 95 men with azoospermia, including 51 with obstructive azoospermia and 44 with nonobstructive azoospermia. Sperm motility was determined at initial collection and following incubation for 24 or 48 hours in processing media or Ham's F10 + protein. A mixed regression model controlling for testis side, media and baseline motility was created to analyze the change in motility between 24 and 48 hours. RESULTS: Mean motility improved from 3% to 20% at 24 hours and 25% at 48 hours for OA cases and from 0% to 5% at 24 hours and 11% at 48 hours for nonobstructive azoospermia cases. The improvement in motility from 24 to 48 hours was significant for obstructive azoospermia cases (p = 0.001). While media was a nonsignificant factor in regression models, when patients were grouped into categories of motility change there was a significantly better response to F10 compared to processing media (p = 0.03). CONCLUSIONS: Incubation in processing media or Ham's F10 + albumin media improves sperm motility with significant improvement noted between 24 and 48 hours for obstructive azoospermia cases. Ham's F10 + albumin media may provide extra benefit for cases of nonobstructive azoospermia or nerve injury. These results suggest the ideal timing of oocyte retrieval for intracytoplasmic sperm injection correlates with 48-hour sperm incubation for obstructive azoospermia cases, and 24 hours for nonobstructive azoospermia and nerve injury cases.     

Arteriovenous access outcomes in haemodialysis patients with HIV infection.

BACKGROUND: Arteriovenous (AV) grafts in haemodialysis patients usually fail due to thrombosis or infection. There is limited information on whether graft outcomes in HIV-positive haemodialysis patients differ from those in HIV-negative controls. METHODS: Using a prospective, computerized vascular access database, we identified retrospectively 15 HIV-positive dialysis patients having a graft placed during a 6.5-year period (January 1999 to June 2005), and compared their graft outcomes to those observed in 30 age-, sex- and access date-matched HIV-negative control patients. In addition, the outcomes of AV fistulas in 23 HIV-positive patients were compared with those observed in 32 matched HIV-negative controls. RESULTS: Thrombosis-free graft survival was substantially worse among the HIV-positive patients than in the HIV-negative controls (1-year survival, 17% vs 62%). The hazard ratio for graft thrombosis in the HIV-positive patients was 3.22 (95% CI, 1.66-10.32, P = 0.002). Infection-free graft survival was also lower in HIV-positive patients (hazard ratio 3.51; 95% CI, 1.21-18.85, P = 0.025). Finally, cumulative graft survival (from creation until permanent failure) tended to be lower in HIV-positive patients (1 year survival, 41% vs 65%, P = 0.07). The primary failure rate of fistulas (those never usable for dialysis) was similar in HIV-positive patients and in their controls (44% vs 41%, P = 0.83). Cumulative fistula survival was similar for HIV-positive and negative patients (hazard ratio 1.32; 95% CI, 0.65-3.58, P = 0.33). CONCLUSION: AV grafts have inferior outcomes in HIV-positive patients as compared with HIV-negative patients, whereas fistulas have a similar survival in both groups.     

Penile vibratory stimulation and electroejaculation in the treatment of ejaculatory dysfunction

The purpose of this review is to present the current understanding of penile vibratory stimulation (PVS) and electroejaculation (EEJ) procedures and its clinical use in men with ejaculatory dysfunction. Unfortunately, the record of treating such individuals has been quite poor, but within recent years development and refinement of PVS and EEJ in men with spinal cord injury (SCI) has significantly enhanced the prospects for treatment of ejaculatory dysfunction. The majority of spinal cord injured men are not able to produce antegrade ejaculation by masturbation or sexual stimulation. However, approximately 80% of all spinal cord injured men with an intact ejaculatory reflex arc (above T10) can obtain antegrade ejaculation with PVS. Electroejaculation may be successful in obtaining ejaculate from men with all types of SCI, including men who do not have major components of the ejaculatory reflex arc. Because vibratory stimulation is very simple in use, non-invasive, it does not require anaesthesia and is preferred by the patients when compared with EEJ, PVS is recommended to be the first choice of treatment in spinal cord injured men. Furthermore, EEJ has been successfully used to induce ejaculation in men with multiple sclerosis and diabetic neuropathy. Any other conditions which affect the ejaculatory mechanism of the central and/or peripheral nervous system including surgical nerve injury may be treated successfully with EEJ. Finally, for sperm retrieval and sperm cryopreservation before intensive anticancer therapy in pubertal boys, PVS and EEJ have been successfully performed in patients who failed to obtain ejaculation by masturbation. Nearly all data concerning semen characteristics in men with ejaculatory dysfuntion originate from spinal cord injured men. Semen analyses demonstrate low sperm motility rates in the majority of spinal cord injured men. The data give evidence of a decline in spermatogenesis and motility of ejaculated spermatozoa shortly after (few weeks) an acute SCI. Furthermore, it is suggested that some factors in the seminal plasma and/or disordered storage of spermatozoa in the seminal vesicles are mainly responsible for the impaired semen profiles in men with chronic SCI. Home insemination with semen obtained by penile vibratory and introduced intravaginally in order to achieve successful pregnancies may be an option for some spinal cord injured men and their partners. The majority of men will further enhance their fertility potential when using either penile vibratory or EEJ combined with assisted reproduction techniques such as intrauterine insemination or in-vitro fertilization with or without intracytoplasmic sperm injection.     

Fertility of Spinal Cord Injured Males: Effect of Genitourinary Infection and Bladder Management on Results of Electroejaculation

ABSTRACT

Thirty-eight men undergoing electroejaculation (EEJ) procedures for anejaculatory infertility were examined for the presence or absence of infection in urine and semen. In 29 spinal cord injury patients, a high incidence of infected urine and infected semen (41% and 56%, respectively) was seen, in contrast to patients with normal bladder function (0% and 11 %).

Urinary infection was associated with slightly lower sperm quality and lower pregnancy rates (10% vs 30% in the presence of sterile urine). Semen infection had no effect on sperm counts or pregnancy rates. If intermittent self-catheterization (ISC) was used to empty the neurogenic bladder, slightly better sperm quality was seen, the total failure rate was less, and much better pregnancy rates (44%) resulted than for patients using an alternative bladder management (7%).

Antibiotics did not reduce the incidence of urine or semen infection, but did improve sperm counts slightly. Continuous prophylaxis was associated with bacterial resistance to many oral antibiotics and had no advantage over a short course of antibiotics prior to the procedure.

Despite the above associations, the sperm quality in our patient population was never normal compared with that of men who ejaculate normally. We conclude that the low sperm quality seen in electroejaculation specimens from spinal cord injured males is not due entirely to infection or to the type of bladder management. Short courses of antibiotics, instead of continuous antibiotic prophylaxis, may be beneficial. Intermittent catheterization is superior to other methods of neurogenic bladder management in maintaining the fertility of spinal cord injured men.     

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.     

APOE genotype affects black-white responses of high-density lipoprotein cholesterol subspecies to aerobic exercise training

The objective of the study was to determine whether ethnicity interacts with the APOE genotype to influence conventionally measured high-density lipoprotein cholesterol (HDL-C) subfraction levels and nuclear magnetic resonance-measured (HDL_NMR-C) particle size at baseline and after training, and the changes with training. After a 6-week dietary stabilization period, men and postmenopausal women 50 to 75 years old underwent baseline testing (NMR lipid, maximum oxygen consumption, body composition, and genotyping assessments). Tests were repeated after completing 24 weeks of endurance exercise training. At baseline, APOE2/3 blacks had significantly larger particle size (P < .001) and higher total HDL_NMR-C particle concentration (P = .006) than whites. After 6 months of endurance exercise training, APOE2/3 blacks maintained a significantly larger HDL_NMR-C particle size (P < .001) and particle concentration of the large HDL_NMR-C than APOE2/3 whites (P < .001). In multivariate analyses of variance adjusted for demographic and environmental confounding factors and for training-induced changes in lean body mass and intraabdominal fat, the model explained approximately 33% of the observed variability in training-induced improvements in HDL_NMR-C particle size (P = .002), with APOE2/3 blacks having a greater increase in training-induced changes in HDL_NMR-C particle size. In a separate but similarly adjusted model for conventionally measured HDL₂-C, the model explained approximately 49% of the observed variability in training-induced changes in HDL₂-C. Ethnicity interacted with the E2/3 genotype at the APOE gene locus to influence higher baseline and after-training levels, and greater exercise training-induced improvements in the advantageous HDL-C subfractions in blacks than in whites. APOE2/3 blacks may benefit more from aerobic fitness to reduce cardiovascular risk.     

Delayed hemorrhage following endoscopic retrograde sphincterotomy for choledocholithiasis

To define the clinical significance of delayed postsphincterotomy hemorrhage, we reviewed 476 consecutive ERCP procedures performed over a three-year period. Of 250 patients who underwent endoscopic sphincterotomy (ES), five (2%) developed postprocedure hemorrhage, two of whom had immediate, self-limited bleeding that resolved after endoscopic injection of epinephrine and did not require transfusion. The other three had delayed hemorrhage characterized by: onset 20–48 hr after the procedure, melena without hematemesis as the index clinical manifestation of bleeding, and atraumatic balloon extraction of common duct stones. Transfusion of 2–6 units of packed erythrocytes was necessary in each and one patient required surgical hemostasis. Delayed hemorrhage following ERS is an important, frequently severe complication to remember when contemplating performing ERS as an outpatient procedure.