Laparoscopic-assisted peritoneal dialysis catheter placement: a microinvasive technique

Background Peritoneal dialysis is an alternate form of dialysis for patients with end-stage renal disease (ESRD). Although not as widely used as hemodialysis, peritoneal dialysis (PD) has clear advantages, especially those related to patient satisfaction and simplicity. The purpose of our study was to describe and look at the results of a microinvasive technique for placement of peritoneal dialysis catheters under laparoscopy. Methods From August 2003 to January 2006, 12 patients with ESRD underwent laparoscopic-assisted peritoneal dialysis (LAPD) catheter placement with the microinvasive technique at our institution. Data collected included age, gender, underlying renal disease, and length of operation. Followup was completed for all patients (at least 6 months) and catheter-related morbidity and mortality were also analyzed. Results There were 13 procedures performed (one patient had LAPD catheter placement twice). The average age was 45 years and the most common cause of ESRD was uncontrolled arterial hypertension. Procedural time averaged 33.6 min (range = 24–50 min). Peritoneal dialysis was introduced two weeks after the procedure and no dialysate leaks were observed. There were two catheter-related morbidities; both were catheter exit-site abscesses, one managed surgically with removal of the PD catheter and the other managed conservately with culture-sensitive antimicrobials. Patient satisfaction was beyond acceptable in 92% of the patients (12 of 13). Average longevity of the catheter was 61 weeks (427 days). There were no mortalities. Conclusion LAPD catheter placement is an easy technique with acceptable catheter longevity and minimal morbidity. The microinvasive technique leads to better patient satisfaction and cosmetic outcome without affecting its function. Therefore, we believe that by promoting microinvasive LAPD catheter placement, PD will gain more acceptance among doctors and patients.     

Cryptorchidism and hypospadias

PURPOSE: We quantified the burden of cryptorchidism and hypospadias in the United States by identifying trends in the use of health care resources and estimating the economic impact of the disease. MATERIALS AND METHODS: The analytical methods used to generate these results were described previously. RESULTS: Cryptorchidism is managed almost exclusively in the outpatient setting and insufficient data were available on inpatient health care use. Annual inpatient hospitalizations for hypospadias decreased by 75% between 1994 and 2000 from 2,669 (2.2/100,000 children) to 849 (0.6/100,000). Between 1992 and 2000 there were 611,647 physician office visits (96/100,000 per year) with undescended testis listed as the primary diagnosis. The rate of physician office visits for hypospadias by commercially insured boys younger than 3 years increased significantly from 429/100,000 in 1994 to 655/100,000 in 2002. The annualized rate of 18/100,000 in 1994 to 1996 remained relatively constant during these 3 years. Orchiopexy rates were highest in 0 to 2-year-old children, as generally recommended, but a substantial minority of these procedures was done in 3 to 10-year-old children. Geographic variation was noted with higher ambulatory surgery rates in the Northeast and Midwest than in the South and West. Data on commercially insured boys younger than 3 years revealed a 1.5-fold overall increase in the rate of hypospadias surgery from 321/100,000 in 1994 to 468/100,000 in 2002, reflecting the known increase in hypospadias incidence in the United States during the late 1990 s. CONCLUSIONS: Average cost per hospitalization for hypospadias exceeded $5,389 with costs per case higher in children 3 years or older, although there were more cases in children younger than 3 years. The cost per case of hypospadias was higher in the Northeast and South than in the other regions. Data on cryptorchidism are too sparse to provide insights into its downstream economic costs.     

Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee

BACKGROUND: TORCH (Towards a Revolution in COPD Health) is an international multicentre, randomised, placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease (COPD). The primary outcome is all-cause mortality. Cause-specific mortality and deaths related to COPD are additional outcome measures, but systematic methods for ascertainment of these outcomes have not previously been described. METHODS: A Clinical Endpoint Committee (CEC) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic, unbiased and independent manner. The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD-relatedness; the independent review of cases by all members with development of a consensus opinion; and a substantial infrastructure to collect medical information. RESULTS: 911 deaths were reviewed and consensus was reached in all. Cause-specific mortality was: cardiovascular 27%, respiratory 35%, cancer 21%, other 10% and unknown 8%. 40% of deaths were definitely or probably related to COPD. Adjudications were identical in 83% of blindly re-adjudicated cases (kappa = 0.80). COPD-relatedness was reproduced 84% of the time (kappa = 0.73). The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52% of cases. CONCLUSION: A CEC can provide standardised, reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators.     

The effect of systemic anticoagulation in patients undergoing angioaccess surgery

The benefit of intravenous heparin as an anticoagulant to avoid thrombotic complications during angioaccess surgery for hemodialysis is unknown. We prospectively randomized 115 consecutive patients referred to our institution for permanent hemodialysis access to receive systemic anticoagulation or no anticoagulation during angioaccess surgery. Patient demographics, comorbid conditions, procedure time, complications, and patency were recorded in accordance with standards recommended by the Society for Vascular Surgery. Of the 115 patients randomized, 58 received no anticoagulation and 57 received systemic anticoagulation with intravenous heparin. Arteriovenous fistulas were created in 84 patients and 31 arteriovenous grafts were inserted. Operative times were longer for grafts compared to fistulas, but there were no significant differences in operative times between patients receiving anticoagulation and those not (p = 0.31). Perioperative bleeding complications were more common in patients receiving heparin (p = 0.008). The primary 30-day patency was 84% for patients receiving heparin and 86% for those not (p = 0.79). The 3-month functional patency was 68% for both groups (p = 0.99). Age, gender, operative time, and incidence of bleeding complications had no impact on patency. In our experience, systemic anticoagulation for angioaccess surgery is associated with an increased incidence of bleeding complications and offers no advantage in terms of early patency.     

Assessment of anandamide's pharmacological effects in mice deficient of both fatty acid amide hydrolase and cannabinoid CB1 receptors

In the present study, we investigated whether anandamide produces its behavioral effects through a cannabinoid CB(1) receptor mechanism of action. The behavioral effects of anandamide were evaluated in mice that lacked both fatty acid amide hydrolase (FAAH) and cannabinoid CB(1) receptors (DKO) as compared to FAAH (-/-), cannabinoid CB(1) (-/-), and wild type mice. Anandamide produced analgesia, catalepsy, and hypothermia in FAAH (-/-) mice, but failed to elicit any of these effects in the other three genotypes. In contrast, anandamide decreased locomotor behavior regardless of genotype, suggesting the involvement of multiple mechanisms of action, including its products of degradation. These findings indicate that the cannabinoid CB(1) receptor is the predominant target mediating anandamide's behavioral effects.     

Protean agonism at the dopamine D2 receptor: (S)-3-(3-hydroxyphenyl)-N-propylpiperidine is an agonist for activation of Go1 but an antagonist/inverse agonist for Gi1,Gi2, and Gi3

A range of ligands displayed agonism at the long isoform of the human dopamine D(2) receptor, whether using receptor-G protein fusions or membranes of cells in which pertussis toxin-resistant mutants of individual Galpha(i)-family G proteins could be expressed in an inducible fashion. Varying degrees of efficacy were observed for individual ligands as monitored by their capacity to load [(35)S]GTPgammaS onto each of Galpha(i1),Galpha(i2),Galpha(i3), and Galpha(o1). By contrast, (S)-(-)-3-(3-hydroxyphenyl)-N-propylpiperidine was a partial agonist when Galpha(o1) was the target G protein but an antagonist/inverse agonist at Galpha(i1),Galpha(i2), and Galpha(i3). In ligand binding assays, dopamine identified both high- and low-affinity states at each of the dopamine D(2) receptor-G protein fusion proteins, and the high-affinity state was eliminated by guanine nucleotide. (S)-(-)-3-(3-hydroxyphenyl)-N-propylpiperidine bound to an apparent single state of the constructs in which the D(2) receptor was fused to Galpha(i1),Galpha(i2), or Galpha(i3). However, it bound to distinct high- and low-affinity states of the D(2) receptor-Galpha(o1) fusion, with the high-affinity state being eliminated by guanine nucleotide. Likewise, although dopamine identified guanine nucleotide-sensitive high-affinity states of the D(2) receptor when expression of pertussis toxin-resistant forms of each of Galpha(i1), Galpha(i2), Galpha(i3), and Galpha(o1) was induced, (S)-(-)-3-(3-hydroxyphenyl)-N-propylpiperidine identified a high-affinity site only in the presence of Galpha(o1). p-Tyramine displayed a protean ligand profile similar to that of (S)-(-)-3-(3-hydroxyphenyl)-N-propylpiperidine but with lower potency. These results demonstrate (S)-(-)-3-(3-hydroxyphenyl)-N-propylpiperidine to be a protean agonist at the D(2) receptor and may explain in vivo actions of this ligand.     

Cystine-glutamate transporter SLC7A11 mediates resistance to geldanamycin but not to 17-(allylamino)-17-demethoxygeldanamycin

The cystine-glutamate transporter SLC7A11 has been implicated in chemoresistance, by supplying cystine to the cell for glutathione maintenance. In the NCI-60 cell panel, SLC7A11 expression shows negative correlation with growth inhibitory potency of geldanamycin but not with its analog 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), which differs in the C-17 substituent in that the the methoxy moiety of geldanamycin is replaced by an amino group. Structure and potency analysis classified 18 geldanamycin analogs into two subgroups, "17-O/H" (C-17 methoxy or unsubstituted) and "17-N" (C-17 amino), showing distinct SLC7A11 correlation. We used three 17-O/H analogs and four 17-N analogs to test the role of the 17-substituents in susceptibility to SLC7A11-mediated resistance. In A549 cells, which are resistant to geldanamycin and strongly express SLC7A11, inhibition of SLC7A11 by (S)-4-carboxyphenylglycine or small interfering RNA increased sensitivity to 17-O/H, but had no effect on 17-N analogs. Ectopic expression of SLC7A11 in HepG2 cells, which are sensitive to geldanamycin and express low SLC7A11, confers resistance to geldanamycin, but not to 17-AAG. Antioxidant N-acetylcysteine, a precursor for glutathione synthesis, completely suppressed cytotoxic effects of 17-O/H but had no effect on 17-N analogs, whereas the prooxidant ascorbic acid had the opposite effect. Compared with 17-AAG, geldanamycin led to significantly more intracellular reactive oxygen species (ROS) production, which was quenched by addition of N-acetylcysteine. We conclude that SLC7A11 confers resistance selectively to 17-O/H (e.g., geldanamycin) but not to 17-N (e.g., 17-AAG) analogs partly as a result of differential dependence on ROS for cytotoxicity. Distinct mechanisms could significantly affect antitumor response and organ toxicity of these compounds in vivo.     

The Effect of Medicaid Managed Care on Prenatal Care: The Case of Puerto Rico

Objectives From 1994 to the year 2000 the government of Puerto Rico implemented a health care reform which included the mandatory enrollment of the entire Medicaid eligible population under Medicaid managed care (MMC) plans. This study assessed the effect of MMC on the use, initiation, utilization, and adequacy of prenatal care services over the reform period. Methods Using the vital records of all infants born alive in Puerto Rico from the year 1995–2000, a series of bivariate and multivariate analyses were conducted to assess the effect of insurance status (traditional Medicaid, MMC, private insurance and uninsured) on prenatal care utilization patterns. In order to assess the potential influence of selection bias in generating the health insurance assignments, propensity scores (PS) were estimated and entered into the multivariate regressions. Results MMC had a generally positive effect on the frequency and adequacy of prenatal care when compared with the experience of women covered by traditional Medicaid. However, the PS analyses suggested that self-selection may have generated part of the observed beneficial effects. Also, MMC reduced but did not eliminate the gap in the amount and adequacy of prenatal care received by pregnant women covered by Medicaid when compared to their counterparts covered by private insurance. Conclusions The Puerto Rico Health Reform to implement MMC for pregnant women was associated with a general improvement in prenatal care utilization. However, continued progress will be necessary for women covered by Medicaid to reach prenatal care utilization levels experienced by privately insured women.     

Polypyrrole-coated electrodes for the delivery of charge and neurotrophins to cochlear neurons

Sensorineural hearing loss is associated with gradual degeneration of spiral ganglion neurons (SGNs), compromising hearing outcomes with cochlear implant use. Combination of neurotrophin delivery to the cochlea and electrical stimulation from a cochlear implant protects SGNs, prompting research into neurotrophin-eluting polymer electrode coatings. The electrically conducting polypyrrole/para-toluene sulfonate containing neurotrophin-3 (Ppy/pTS/NT3) was applied to 1.7 mm² cochlear implant electrodes. Ppy/pTS/NT3-coated electrode arrays stored 2 ng NT3 and released 0.1 ng/day with electrical stimulation. Guinea pigs were implanted with Ppy/pTS or Ppy/pTS/NT3 electrode arrays two weeks after deafening via aminoglycosides. The electrodes of a subgroup of these guinea pigs were electrically stimulated for 8 h/day for 2 weeks. There was a loss of SGNs in the implanted cochleae of guinea pigs with Ppy/pTS-coated electrodes indicative of electrode insertion damage. However, guinea pigs implanted with electrically stimulated Ppy/pTS/NT3-coated electrodes had lower electrically-evoked auditory brainstem response thresholds and greater SGN densities in implanted cochleae compared to non-implanted cochleae and compared to animals implanted with Ppy/pTS-coated electrodes (p < 0.05). Ppy/pTS/NT3 did not exacerbate fibrous tissue formation and did not affect electrode impedance. Drug-eluting conducting polymer coatings on cochlear implant electrodes present a clinically viable method to promote preservation of SGNs without adversely affecting the function of the cochlear implant.