Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure

Endothelial dysfunction and arterial stiffness are major determinants of cardiovascular risk in patients with end-stage renal failure (ESRF). Microparticles are membrane fragments shed from damaged or activated cells. Because microparticles can affect endothelial cells, this study investigated the relationship between circulating microparticles and arterial dysfunction in patients with ESRF and identified the cellular origin of microparticles associated with these alterations. Flow cytometry analysis of platelet-free plasma from 44 patients with ESRF indicated that circulating levels of Annexin V+ microparticles were increased compared with 32 healthy subjects, as were levels of microparticles derived from endothelial cells (three-fold), platelets (16.5-fold), and erythrocytes (1.6-fold). However, when arterial function was evaluated noninvasively in patients with ESRF, only endothelial microparticle levels correlated highly with loss of flow-mediated dilation (r = -0.543; P = 0.004), increased aortic pulse wave velocity (r = 0.642, P < 0.0001), and increased common carotid artery augmentation index (r = 0.463, P = 0.0017), whereas platelet-derived, erythrocyte-derived, and Annexin V+ microparticle levels did not. In vitro, microparticles from patients with ESRF impaired endothelium-dependent relaxations and cyclic guanosine monophosphate generation, whereas microparticles from healthy subjects did not. Moreover, in vitro endothelial dysfunction correlated with endothelial-derived (r = 0.891; P = 0.003) but not platelet-derived microparticle concentrations. In fact, endothelial microparticles alone decreased endothelial nitric oxide release by 59 +/- 7% (P = 0.025). This study suggests that circulating microparticles of endothelial origin are tightly associated with endothelial dysfunction and arterial dysfunction in ESRF.     

Thoracic complications during urological laparoscopy

PURPOSE: We documented thoracic related complications during urological laparoscopic surgery. MATERIALS AND METHODS: A total of 1129 patients underwent major urological laparoscopic procedures in a 5-year period. Operative reports and postoperative radiographic reports were retrospectively reviewed to identify patients with thoracic related medical and surgical sequelae. Of the patients 619 (55%) underwent at least 1 chest x-ray in the immediate or early postoperative period. In the remaining 510 patients (45%) there was no clinical indication to perform chest x-ray. RESULTS: Of 619 patients undergoing chest x-ray 438 (71%) were completely normal. Medical pulmonary complications, surgical thoracic complications and subclinical, incidentally detected gas collections in the chest were identified in 12.6%, 0.5% and 5.5% of patients, respectively. Medical complications in 12.6% of cases included pulmonary infiltrate/atelectasis in 9.7%, pleural effusion in 4.8% and pulmonary embolus in 0.3%. Surgical complications included symptomatic pneumothorax in 4 patients (0.35%), hemothorax in 1 (0.08%) and chylothorax in 1 (0.08%). Subclinical abnormal thoracic gas collections were radiographically noted in 34 of the 619 patients (5.5%) on chest x-ray, including pneumomediastinum in 19 (3.1%), pneumothorax in 10 (1.6%) and pneumopericardium in 5 (0.8%). Overall 36 of 40 (90%) thoracic surgical complications (3) and subclinical, incidentally detected gas collections (33) occurred during retroperitoneal laparoscopy. Re-intervention was necessary in 6 patients (0.5%), namely pulmonary embolus requiring vena caval filter placement in 3 (0.3%), pneumothorax requiring a chest tube in 2 (0.17%) and hemothorax requiring emergency open thoracotomy in 1 (0.08%). No patient underwent open conversion to complete the initial proposed operation. CONCLUSIONS: Due to its high solubility the expectant management of incidental CO2 pneumothorax, pneumopericardium and pneumomediastinum is recommended initially in the clinically stable patient. Inadvertent diaphragmatic entry can be satisfactorily repaired laparoscopically without open conversion. Although it is rare, surgical thoracic complications are potentially life threatening, requiring prompt identification and management.     

Prenatal Androgenization Affects Gender-Related Behavior But Not Gender Identity in 5–12-Year-Old Girls with Congenital Adrenal Hyperplasia

Gender assignment of children with intersexuality and related conditions has recently become highly controversial. On the basis of extensive animal research and a few human case reports, some authors have proposed the putative masculinization of the brain by prenatal hormones-indicated by the degree of genital masculinization-as the decisive criterion of gender assignment and have derived the recommendation that 46,XX newborns with congenital adrenal hyperplasia (CAH) and full genital masculinization should be assigned to the male gender. The purpose of this study was to test in CAH girls of middle childhood the assumption that prenatal androgens determine the development of gender identity. Fifteen girls with CAH (range of genital Prader stage, 2-4/5), 30 control girls, and 16 control boys (age range, 5-12 years) underwent 2 gender-play observation sessions, and a gender identity interview yielding scales of gender confusion/dysphoria. About half a year earlier, mothers had completed 2 questionnaires concerning their children's gender-related behavior. The results showed that, as expected, CAH girls scored more masculine than control girls on all scales measuring gender-related behavior, with robust effect sizes. By contrast, neither conventionally significant differences nor trends were found on the 3 scales of the gender identity interview. We conclude that prenatal androgenization of 46,XX fetuses leads to marked masculinization of later gender-related behavior, but the absence of any increased gender-identity confusion/dysphoria does not indicate a direct determination of gender identity by prenatal androgens and does not, therefore, support a male gender assignment at birth of the most markedly masculinized girls.     

Ureteral tissue balloon expansion for laparoscopic bladder augmentation: survival study

BACKGROUND AND PURPOSE: The search for the perfect urinary bladder substitute continues. Despite their inherent limitations, intestinal segments remain the commonest material for bladder reconstruction. The ureter, with its transitional epithelium, may be the ideal tissue to augment the bladder. Ikeguchi et al reported the feasibility of chronic ureteral balloon expansion by open surgery (J Urol 1998;159:1665). Herein, we propose a completely minimally invasive approach to balloon overdilate a segment of juxtavesical ureter incrementally and to use this in-line tissue-expanded ureteral patch to augment the bladder laparoscopically. MATERIALS AND METHODS: In five female pigs, a novel ureteral expansion balloon device (Microvasive, MA) was inserted percutaneously and advanced antegrade into the juxtavesical ureter. The device has two channels: one for balloon inflation and the other for draining the kidney. After progressive ureteral expansion over a 3- to 4-week period, laparoscopic augmentation ureterocystoplasty was performed. Animals were euthanized at 15 days (N = 1), 1 month (N = 1), 2 months (N = 1), and 3 months (N = 2). RESULTS: Percutaneous balloon device placement was technically successful in all five cases (mean operating room time 52 minutes). The mean volume of the tissue-expanded ureter at 1, 2, and 3 weeks was 12.9 cc, 60.3 cc, and 171.8 cc, respectively. Laparoscopic augmentation ureterocystoplasty with (N = 3) or without (N = 2) concomitant subtotal cystectomy was technically successful in all five cases without any open conversion. The mean operative time was 126.5 minutes, and the mean blood loss was 29 mL. Postoperative complications consisted of one case each of pyelonephritis and ureteral stricture. At autopsy, the mean capacity of the bladder was 574 mL, and the P(ves) at maximum capacity was 14 cm H(2)O. Histologic examination of the tissue-expanded ureter revealed regenerated transitional epithelium and muscle hypertrophy. CONCLUSIONS: Chronic ureteral tissue expansion can be carried out safely and efficaciously. The expanded tissue is thick, healthy, and vascular, with histologic features of normal transitional epithelium and muscle hypertrophy and hyperplasia. This expanded ureteral tissue can be used to augment the bladder with laparoscopic techniques. Such augmented bladders do not show significant shrinkage and possess urodynamic characteristic of normal capacity and normal compliance over a follow-up of 3 months.     

Laparoscopic radical nephrectomy for cancer with level I renal vein involvement

PURPOSE: Venous involvement develops in 5% to 10% of patients with renal cell carcinoma and is generally considered a relative contraindication to laparoscopic radical nephrectomy. To our knowledge we report the initial clinical series of laparoscopic radical nephrectomy for renal cell carcinoma associated with level I renal vein thrombus. MATERIALS AND METHODS: At our 2 institutions 8 patients each underwent laparoscopic radical nephrectomy for level I microscopic renal vein thrombus (group 1) and level I gross thrombus (group 2). In all 8 group 2 patients the level I thrombus was preoperatively diagnosed by computerized tomography. Mean renal tumor size in groups 1 and 2 was 7.8 and 12.4 cm., respectively. After controlling the renal artery the renal vein was secured by firing an endoscopic gastrointestinal anastomosis stapler on its collapsed, uninvolved proximal part adjacent to the vena cava. Intraoperative, postoperative and pathological parameters were assessed in the 2 groups. RESULTS: In group 1 laparoscopic radical nephrectomy was technically successful in all 8 patients. Mean operative time was 3.1 hours, mean estimated blood loss was 382 cc and mean hospital stay was 1.9 days. In 1 patient each a soft tissue and a vascular margin was positive for cancer. At a mean follow up of 19.5 months (range 2 to 36) metastatic disease occurred in 3 cases (38%). In group 2 laparoscopic radical nephrectomy was technically successful in 7 cases with open conversion in 1. Mean operative time was 3.3 hours, mean estimated blood loss was 354 cc and mean hospital stay was 2.3 days. Surgical soft tissue and the renal vein vascular margin of the transected vein were negative for cancer in all 8 cases. At a mean followup of 9.4 months (range 5 to 16) pulmonary metastasis developed in 1 patient (13%). CONCLUSIONS: Although it is an advanced procedure, laparoscopic radical nephrectomy in patients with level I renal vein thrombus is feasible, safe and follows established oncological principles.