Urological complications in 1,223 kidney transplantations.

INTRODUCTION: Urological complications after kidney transplantation may lead to graft loss. In this study, we retrospectively reviewed urological complications in 1,223 kidney transplantations that were performed at our institution. MATERIALS AND METHODS: The occurrence of urological complications such as urine leakage, ureteral obstruction and vesicoureteral reflux (VUR) according to the different way of urinary tract reconstruction, ureteroneocystostomy (U-C) and ureteroureterostomy (U-U), was studied. RESULTS: Urological complications were encountered in 92 (7.5%) cases, including urine leakage (n = 43, 3.5%), ureteral obstruction (n = 35, 2.9%) and VUR (n = 14, 1.1%). 75 cases (7.9%) were in the U-C group and 17 cases (6.2%) in the U-U group. 91 recipients were successfully treated, and 1 patient lost the graft due to kidney pelvis and ureteral necrosis. There was no recipient loss due to these complications. For recipients with urological complications, the 1- and 3-year survival rates were 90 and 88% for recipients and 87 and 82% for grafts, respectively. CONCLUSIONS: After U-U, the same number of overall incidences of urological complications is observed as after U-C; however, a decrease in the number of incidences of urine leakage is apparent. Therefore, U-U is a good first option with a greater success rate of resolving ureteral stenosis with endourology and no risk of VUR.

Immunoelectron microscopic localization of mannose-terminal glucocerebrosidase in lysosomes of rat liver Kupffer cells.

Knowledge of the cellular distribution and subcellular localization of mannose-terminal glucocerebrosidase after intravenous infusion is necessary for understanding the efficacy of targeted enzyme replacement therapy for Gaucher's disease. Selective uptake of mannose-terminal glucocerebrosidase by Kupffer cells in rat liver has been previously demonstrated biochemically. In this study we used immunohistochemical and immunogold labeling techniques to provide direct visual proof for the localization of the delivered enzyme. Light microscopy confirmed biochemical data identifying non-parenchymal cells as the primary target of the modified glucocerebrosidase. Using a primary antibody specific for glucocerebrosidase and a secondary gold-conjugated antibody, we used immunoelectron microscopy to quantify the extent and distribution of exogenous enzyme in various cell types in rat liver and its localization within their respective subcellular organelles. Thirty minutes after intravenous administration of mannose-terminal glucocerebrosidase, enzyme was localized primarily in lysosomes of Kupffer cells. Of eight intact Kupffer cells counted, 16 of 21 lysosomes (78%) contained immunogold conjugates (average concentration 293 gold particles/micron 2). Of 589 particles counted in these lysosomes, 485 (82%) were localized within the lumen of the lysosome; only 104 (18%) were membrane-associated. Five of the 21 lysosomes counted were negative for gold. No gold particles were found in the mitochondria of Kupffer cells and very few particles (8.2/microns 2) were found over the nucleus. The density of gold particles was also low over the nucleus (7.2/microns 2), mitochondria (8.8/microns 2), and lysosomes (7.9/microns 2) of hepatocytes. No specific labeling was observed in erythrocytes, platelets, lymphocytes, pit cells, fat-storing cells, or bile duct. Background labeling of control liver sections from rats receiving saline injection was 8.2 +/- 1.4 gold particles/microns 2. We conclude that mannose-terminal glucocerebrosidase is delivered to the lysosomes of Kupffer cells in liver and that it is distributed both within the lumen (82%) and over the membrane (18%) of the lysosome, with a slight preferential association with the membrane. These findings may provide insights into the design of more effective therapeutic enzyme preparations for the treatment of Gaucher's disease.

Analysis of 541 cases of occupational acute chemical injuries in a large petrochemical company in China.

The authors carried out a descriptive analysis of acute chemical intoxication in a large petrochemical corporation with 38,000 employees, located in a suburban district of Shanghai, China, to determine the chemicals involved and the primary causes of the incidents. Between 1977 and 1997, 350 cases of acute chemical-intoxication were recorded, resulting in a total of 541 workers with symptoms. Of these, 483 were male and 58, female, with over half the victims under 30 years old. Two hundred and seventy-five cases were serious enough to necessitate hospital admission. There were 266 cases of chemical irritation or inhalation responses (49.2%), 215 cases of mild chemical poisoning (39.7%), 31 cases of moderate poisoning (5.7%), and 29 cases resulting in critical injury (5.4%), including eight deaths (1.5%). The main causes of injury reported by patients were lack of training about safety (63%) and equipment failure (23%). The chemicals involved were asphyxiating gases (302 cases; 55.8%), irritating gases (111 cases; 20.5%), and other toxins. Intervention strategies for the prevention of acute chemical exposures were suggested to the corporation.

Clinical analysis of the characterization of magnetic resonance imaging in 102 cases of refractory haematospermia.

To analyze the pathogenesis of persistent and refractory haematospermia and to evaluate the aetiological diagnostic value of magnetic resonance imaging (MRI) for this type of haematospermia. Clinical data from 102 patients with persistent and refractory haematospermia was retrospectively analysed. Data collected included history, symptoms, as well as ultrasound and MRI of the morphological features of the bilateral seminal vesicles (SV) and ejaculatory duct (ED) areas. Criteria for inclusion were haematospermia symptoms that occurred more than six times, that lasted more than 6 months, and that did not improve after >1 month of conservative treatment. Patients underwent seminal vesiculoscopy with a post-surgery follow-up of 3-48 months [average (18.1 ± 10.3) months]. Of the 102 patients that underwent MRI examination, data from 88 patients (86.3%) showed typical and characteristic changes in the ED area, including the signal intensity changes in 60 (58.8%), SV volume changes in 32(31.4%), the formation of cysts such as prostatic utricular cysts in 27 (26.5%), Müllerian cysts in 4 (3.9%), ED cysts in 5 (4.9%) and a SV cyst in 1(1.0%). The MRI findings were confirmed by seminal vesiculoscopy and all patients received appropriate treatment. In 14 patients (13.7%), no obvious abnormal changes were observed with MRIs, however, these patients were diagnosed and successfully managed using seminal vesiculoscopy. Some degrees of ED obstruction was usually found during surgery. The symptoms of haematospermia disappeared 1-2 months after surgery in all patients. Two patients had a recurrence of haematospermia, underwent the same treatment, and recovered during the follow-up period. The aetiology of the most cases of the refractory haematospermia can be distinguished using the three-dimensional MRI. Typical abnormalities observed on MR images are signal intensity, SV volume changes and cyst formation. MRI has significant etiological diagnostic value and provides reliable information for the subsequent treatment of patients with persistent and refractory haematospermia.

Heme oxygenase-1 expression and its significance for acute rejection following kidney transplantation in rats.

OBJECTIVE: To analyze rejection and antiapoptotic effects of heme oxygenase-1 (HO-1) in kidney transplantations, to investigate the protective effects of endogenous HO-1 induced by hemin on acute rat kidney allograft rejection. METHODS: We selected 27 Brown-Norway rats and 27 male Lewis rats as donors and recipients, respectively, randomly dividing them into three groups: kidney transplantation alone, hemin treatment group, and cyclosporine (CsA) group (n = 18). Six recipient rats were harvested on the first, fifth, or seventh days after operation among each group to examine histopathologic changes in renal tissue, HO-1 protein expression, and acute rejection as well as to measure serum creatinine values. RESULTS: HO-1 expression in both the kidney transplantation model group and the hemin-induced groups were higher compared with the CsA group (P < .05-.01). The expression increased with the aggravation of rejection; the expression in the CsA group also increased after transplantation but was obviously lower than that of the hemin-induced group (P < .01). The rejection process was relatively mild as indenset by histopathologic examination. The serum creatinine levels among the hemin-induced group were lower compared to the kidney transplantation control group (P < .05), but higher compared to the CsA group (P < .05). CONCLUSION: HO-1 provided protection of allografts against rejection in rats, but such effects were poorer than those achieved using potent immunosuppressive agents like CsA.

Acute femoral neuropathy following renal transplantation: a retrospective, multicenter study in China.

BACKGROUND: We investigated the relationship between the mode and duration of iliac artery anastomosis and acute femoral neuropathy (AFN). METHODS: A retrospective analysis was performed for 83 AFN cases from 6 transplantation centers in China. The incidence and nature of dysfunction of AFN were classified based upon the duration of iliac arterial anastomosis. No prisoners were used, and no organs from prisoners were used to obtain the data. RESULTS: The incidence of AFN was 3.6% (53/1,449) in internal iliac anastomosis (group 1), 3.1% (11/346) in external iliac anastomosis (group 2) (P > .05 vs. group 1), and was 54.2% (19/35) in internal iliac ligation with external iliac anastomosis (group 3 P < .01 vs. groups 1 and 2). In group 1, the duration of the arterial anastomosis was 20 minutes in 52 cases (98.1%). In group 2, the duration of arterial anastomosis was 20 minutes in 10 cases (91%). In group 3, the duration of the arterial anastomosis was >20 minutes in all cases; 20 cases showed injury to the iliolumbar or deep iliac circumflex artery. CONCLUSION: The incidence of AFN was associated with the selection of iliac arteries, the duration of the arterial anastomosis, and an injury to the iliolumbar or deep iliac circumflex artery.

Treatment of urinary fistula after kidney transplantation.

Urinary fistula is a common complication after kidney transplantation and may lead to graft loss and patient death. Its current incidence ranges from 1.2% to 8.9%. From December 1993 to April 2007, 1223 kidney transplant procedures were performed by our kidney transplantation team. In 948 recipients (group 1), we performed an extravesical ureteroneocystostomy, and in 275 recipients (group 2), a terminoterminal ureteroureterostomy (UU). We observed urinary fistulas in 43 patients (3.5%), with mean onset at 6 days (range, 3-20 days) posttransplantation. Urinary fistula was significantly more common in group 1 compared with group 2 (4.1% and 1.5%, respectively; P < .05). The distal ureteral necrosis was the major frequent cause of urinary fistula (n = 34; 76.7%), which required either a second ureteroneocystostomy or UU using the native ureter. Of these 21 fistulas, including 10 recurrent fistulaes, were successfully treated with pedicled omentum covering the anastomotic stoma. Conservative treatment with a stent and Foley catheter drainage for 1 to 2 weeks was successful in 8 patients. All patients with a urinary fistula regained normal graft function except 1 in whom transplant nephrectomy was necessary because of pelvic and ureteral necrosis. There was no recipient loss secondary to urinary fistula. In conclusion, UU can decrease the incidence of urinary fistula after kidney transplantation. Most urinary fistulas require surgical management; and pedicled omentum is useful to repair the fistula.

Studies on the turnover of exogenous mannose-terminal glucocerebrosidase in rat liver lysosomes.

Mannose-terminal glucocerebrosidase prepared by exoglycosidase digestion of human placental glucocerebrosidase is reported effective in the treatment of patients with type 1 Gaucher's disease [Barton et al. (1991); N Engl J Med 324:1464-1470]. However, the amount of enzyme that is necessary for therapeutic effect is much higher than would be predicted from in vitro activity measurements. We have investigated the fate of infused enzyme following intravenous administration in Sprague-Dawley rats. In this model system, the enzyme is rapidly cleared from the plasma compartment by receptor-mediated endocytosis via the mannose-specific receptor present on reticuloendothelial cells. Enzyme activity measured in rat liver biopsy specimens at various times post-infusion revealed a rapid initial loss of approximately one-half of the maximum delivered enzyme in the first hour followed by a slower decay with a half-life of approximately 6-8 h. The loss in enzyme activity is paralleled by a loss in enzyme protein when analyzed by Western blots. There is no evidence for return of enzyme activity or inactive enzyme protein to the plasma. Incomplete integration into the lysosomal membrane was demonstrated by the use of differential extraction of purified rat liver lysosomes to distinguish between lumenal and membrane bound enzyme. Immunoelectron microscopy of rat liver following infusion of mannose-terminal glucocerebrosidase confirmed localization of the delivered enzyme primarily within the lumen of the lysosomes of Kupffer cells and to a lesser extent associated with the lysosomal membrane. Enzyme activity was stable in isolated rat liver lysosomes preloaded with mannose-terminal glucocerebrosidase and incubated in the absence or presence of ATP. Acidification of the lysosomes to pH 3 results in a rapid loss of enzyme activity and protein; however, the relationship between the in vitro loss and the loss in enzyme activity in intact liver is not clear. We conclude from these studies that rapid intracellular degradation of administered glucocerebrosidase is the prime factor responsible for the high dose required for effective treatment of Gaucher's disease.

Suppression of the immune response to immunotoxins with anti-CD4 monoclonal antibodies.

Treatment of normal mice with a mAb to CD4 (GK1.5) was explored as a means of inhibiting the antibody response to an immunotoxin. Three days of pretreatment with 200 micrograms of GK1.5 completely abrogated the primary antibody response to a 3-micrograms dose of a mutant diphtheria toxin conjugated to an anti-transferrin receptor antibody. The same dose and schedule of anti-CD4 antibody significantly reduced and delayed, but did not prevent, the anamnestic antitoxin response in animals that had been previously primed to the immunotoxin. Three daily injections of anti-CD4 antibodies followed by weekly doses of immunotoxin resulted in a 3-wk delay in the development of antitoxin antibodies, and the kinetics of the antitoxin response correlated with the kinetics of recovery of CD4+ T cells in the spleen and lymph nodes. The antitoxin response to repeated doses of immunotoxin was completely abrogated when anti-CD4 antibodies were given every 2 wk throughout the course of immunotoxin treatment. Thus, transient depletion of Th cells during treatment can block the immune response to an immunotoxin. There was no evidence of tolerance induction with this regimen.