Randomized trial to compare the dosage of darbepoetin alfa by administration route in haemodialysis patients

Aim:   The doses of darbepoetin alfa required to maintain target haemoglobin levels after s.c. or i.v. administration when recombinant human erythropoietin (rHuEpo) treatment was replaced by darbepoetin alfa treatment in haemodialysis (HD) patients were compared.
Methods:   In this prospective, randomized, open-label study, 65 HD patients who were receiving stable SC doses of rHuEpo were switched to an equivalent dose of darbepoetin alfa at a reduced frequency by s.c. or i.v. administration. Patients were randomly assigned to the s.c. group ( n  = 32) or the i.v. group ( n  = 33). Darbepoetin alfa doses were titrated to maintain target haemoglobin levels of 8.0–11.0 g/dL for up to 24 weeks. A period of 20 weeks was used for dose titration and haemoglobin stabilization. This was followed by a 4 week evaluation period.
Results:   The mean haemoglobin concentration during the evaluation period was similar in the s.c. and i.v. groups. The mean dose and mean weight-standardized dose of darbepoetin alfa during the evaluation period tended to be lower in the s.c. group than the i.v. group, although these differences were not statistically significant. The mean weekly darbepoetin alfa dose requirements during the evaluation period significantly decreased in both groups compared to the dose requirements at randomization.
Conclusion:   There is a possibility that s.c. administration of darbepoetin alfa is more efficacious than i.v. administration, but a definite benefit cannot be demonstrated with the current sample size. A bigger sample size is needed to confirm the result.     

Initial Experience with Transvenous Implantable Cardioverter Defibrillator Lead Systems: Operative Morbidity and Mortality

Introduction of non-thoracotomy lead systems™ (Medtronic, Inc.) for the implantable cardioverter defibrillator (ICD) has expanded the indications for use of this mode of therapy. Patients previously considered "too ill" to undergo a thoracotomy as well as patients who are at a high risk for developing sudden death but without previous cardiac arrest, are now considered candidates. The initial experience with the non-thoracotomy lead system at our institution was analyzed for morbidity and mortality. Thirty-four patients underwent attempted intravascular lead implantation, with 30 having initial successful implantation (88.2%). There were 23 males; average ejection fraction (EF) was 38.6%. Three patients developed pulmonary edema and low output immediately after the procedure. Three patients developed electromechanical dissociation during defibrillation threshold testing. A prolonged testing time for the non-thoracotomy lead system was noted when compared to the thoracotomy system (57.39 vs 32.30 min; P < 0.0000). There were more intraoperative morbidities with the non-thoracotomy leads than with the thoracotomy system. There were no perioperative deaths. The potential consequences of prolonged anesthesia time and extensive defibrillation threshold testing should be considered when choosing the route of ICD implant, the type of anesthesia, and the intraoperative testing protocol for each patient.     

Outcome of mid-urethral sling procedures in Korean women with stress urinary incontinence according to body mass index

BACKGROUND: The objective of this study was to determine whether the outcome of mid-urethral sling procedures is influenced by the body mass index of Korean women suffering from stress urinary incontinence (SUI). METHODS: A total of 285 women, ranging in age from 28 to 80 years (mean 55.4), all of whom were followed up for at least 6 months, were ultimately included in this study. The patients were classified as follows: normal weight, 18.5-23 kg/m2; overweight, 23-27.5 kg/m2; obesity, 27.5 kg/m2 or higher. RESULTS: We noted bladder perforations in 11 cases (4.9%, 3.8% and 2.2% in the normal weight, overweight, and obesity groups, respectively; P = 0.449). We determined there to be no significant differences among the three groups with regard to cure rate (P = 0.173). The rates of postoperative urinary retention were 9.9% in the normal weight group, 10.1% in the overweight group, and 15.6% in the obesity group (P = 0.396). We determined there to be no significant differences among the three groups with regard to the persistence of urgency (P = 0.312). Seventy-nine patients (27.7%) exhibited symptoms indicative of voiding disorder (hesitancy, poor flow, or sensations of incomplete emptying). The postoperative development of these voiding symptoms was not significantly different among the three groups (P = 0.106). CONCLUSION: Our results demonstrate both the feasibility and the safety of mid-urethral sling procedures for obese Korean women who suffer from SUI. Additional studies, including prospective randomized trials with longer follow-up periods, will be required in order to confirm these findings.     

Laparoscopic radical cystectomy with extracorporeal urinary diversion: Preliminary experience

AIM: We present our experience with the fi rst eight patients who underwent laparoscopic radical cystectomy with bilateral pelvic lymphadenectomy and extracorporeal urinary diversion. Patients, operative data and the surgical techniques are presented. METHODS: Between June 2003 and April 2004, seven men and one woman with organ-con fi ned muscle-invasive transitional cell carcinoma of the bladder underwent laparoscopic radical cystectomy with urinary diversion. The age range was 41-73 years. Laparoscopic radical cystectomy and bilateral pelvic lymphadenectomy were performed using fi ve ports by a transperitoneal approach. An ileal conduit diversion or ileal W-neobladder was constructed through the site of specimen retrieval. RESULTS: We performed eight radical cystectomies with ileal conduits (six cases) or orthotopic ileal W-neobladders (two cases). Conversion to open surgery was necessary in one due to technical dif fi culty in urethroneobladder anastomosis. Mean operating time was 560 min (range 455-680). Mean estimated blood loss was 675 mL (range 400-1050). Two of the eight patients needed blood transfusion (800 mL each). Mean days to oral intake and ambulation was 4.4 (range 2-6) and 4.1 (range 3-5), respectively. Mean hospital stay was 12.8 days (range 7-28). Mean follow up was 6.1 months (range 4-14). Histopathological examination of the specimens revealed stage T2N0M0 in fi ve cases, T3aN0M0 in one, T3aN1M0 in one and T3bN1M0 in one. No metastases have been detected and all are alive and free of disease. CONCLUSION: Laparoscopic radical cystectomy is feasible, although dif fi cult and technically demanding, and our results are promising. With more experience and improvement of the surgical technique, laparoscopic radical cystectomy with urinary diversion may become an alternative surgical method for treating the selected patients with localized muscle invasive bladder cancer.     

Palmitate and stearate binding to human serum albumin

Multiple binding equilibria of two apparently insoluble ligands, palmitate and stearate, to defatted human serum albumin were studied in a 66 mM sodium phosphate buffer (pH 7.4) at 37 °C, by determination of dialytic exchange rates of ligands among identical equilibrium solutions. The experimental data were analysed by a computerised curve fitting procedure using equilibrium equations for multiple binding of ligands, containing relative binding constants, valid whether the ligands are truly insoluble or are slightly soluble and irrespective of aggregation in aqueous solution. A best-fit set of relative binding constants was found, and subsequently 30 sets of acceptable constants for each set of data in order to evaluate the variation. The data were first fitted by the relative Scatchard's equation, then by the relative, stoichiometric equation. Scatchard's equation is deduced on the presumption that cooperativity is absent while the stoichiometric equation is valid even when cooperativity is present. It was found with palmitate as well as with stearate that the two equations fitted the data equally well, and it was concluded that the observations were compatible with absence of cooperativity. The relative Scatchard binding constants were converted to relative, stoichiometric constants and it was found that the variations of the latter were slight. © Munksgaard 1997.     

Stabilin-2 is involved in lymphocyte adhesion to the hepatic sinusoidal endothelium via the interaction with alphaMbeta2 integrin

Although lymphocyte recirculation to the endothelium plays a critical role in the movement of immune cells from the blood into tissues and sites of inflammation, the mechanisms involved in lymphocyte trafficking via the hepatic circulation have yet to be elucidated fully. In this study, we investigated the role of stabilin-2, which is expressed specifically in the sinusoidal endothelium, in the adhesion of lymphocytes to the hepatic endothelium. Stabilin-2-expressing cells mediate the adhesion of PBLs. This interaction was attributed specifically to the interaction of stabilin-2 with alphaMbeta2 integrin. Using mutant stabilin-2 molecules with deletions in the extracellular domain, we mapped the binding site for alphaMbeta2 integrin to the fasciclin 1 (FAS1) domains of stabilin-2. The specificity of the interaction between alphaMbeta2 integrin and the FAS1 domain was confirmed further by binding assays using neutralizing antibodies. More physiologically, we showed that the down-regulation of stabilin-2 results in the defective binding of lymphocytes to hepatic sinusoidal endothelial cells under conditions of static and physiological flow. Together, these data show that stabilin-2 can reconstitute the lymphocyte-endothelial adhesion cascade under physiological shear stress. We propose a critical role for stabilin-2 in lymphocyte adhesion to specialized endothelia, such as that of the hepatic sinusoid.