The role of free radicals and nitric oxide in the ischemia–reperfusion injury mediated by acute bladder outlet obstruction

Free-radical generation and nitric oxide (NO) generation were detected in the rat bladder following acute bladder outlet obstruction (BOO), and the results were compared with those for vascular ischemia and reperfusion (I-R). Forty male Sprague Dawley rats were used. In the acute BOO plus I-R group (group 1), rats were catheterized with a 3-Fr catheter and an inflated balloon was positioned at the bladder neck. The bladder was overdistended after administration of Ringer solution and furosemide (12 mg/kg, each) for 60 min, and was then drained to allow reperfusion for 30 min. In the acute BOO plus nerve stimulation group (group 2), the pelvic nerve was stimulated in the distended bladder for 60 min (5 s every 5 min, 10 V/0.1 ms, 20 Hz). Pelvic nerve stimulation was performed in nonobstructed animals in group 3. In the I-R group (group 4), the distal aorta was occluded for 60 min followed by reperfusion for 30 min. Sham-operated animals served as the control group (group 5). At the end of the protocols, the levels of hydroxyl and superoxide radicals and NO levels were measured in the bladder tissues with luminol- and lucigenin-enhanced chemiluminescence methods. The results were compared by a one-way analysis of variance test. The levels of hydroxyl radicals were not significantly different between the study groups. In contrast, superoxide radicals and NO levels were significantly increased in both group 1 and group 4 compared with those in control animals (P < 0.05 for all comparisons). Superoxide radical generation in group 2 was comparable to the levels in group 1 (P > 0.05), whereas NO levels were substantially lower than in group 1 (P = 0.06). In summary, vascular I-R causes significant oxidative damage to the bladder. Acute BOO with overdistension of the bladder mimics the effects of true vascular I-R injury. The NO pathway has possibly a major role in I-R-induced bladder damage. Prolonged BOO may therefore significantly enhance the oxidative damage to the bladder and further accentuate the effects of generalized atherosclerotic processes in the elderly adult.     

Short Bowel Syndrome After Continence-Preserving Procedures

The short bowel syndrome (SBS) can result from a variety of conditions, including postoperative complications and malignancy. Continence-preserving operations are generally performed for either ulcerative colitis (UC) or familial polyposis (FAP). These procedures can be associated with high morbidity and the potential for future malignancy. Our aim was to determine the causes and consequences of SBS in patients undergoing these procedures. Twenty-four patients (12 men and 12 women) 18 to 64 years of age were identified with SBS after continence-preserving procedures. Eighteen had pelvic procedures, and six had continent ileostomies. All SBS patients had a proximal ostomy. Remnant length measured <60 cm in five patients, 60–120 cm in ten patients, and >120 cm in nine patients. Overall 13 patients required long-term PN. Four FAP patients with desmoid tumors died. One patient with UC underwent intestinal transplant and expired. Follow-up ranges from 6 to 192 months. Overall 14 patients had UC, nine had FAP, and one had functional disease. Eight patients with an initial diagnosis of UC had subsequent Crohn’s disease necessitating further resection and pouch excision. Eight patients (five with UC, two FAP, and one with functional disease) had postoperative complications, including obstruction or mesenteric ischemia requiring resections. One UC patient developed adenocarcinoma in a continent ileostomy. Seven of the nine FAP patients required resection for desmoid tumors. Six of these underwent resection alone. Three died at 10, 11, and 13 months after SBS from liver failure and sepsis while awaiting transplant. One patient has recurrent desmoid at 30 months, another is alive and well at 48 months, and the other patient, who was not a transplant candidate, died from an unrelated cardiac operation at 23 months. A single patient underwent resection with simultaneous multivisceral transplantation. SBS can develop after continence-preserving procedures. This occurs with inflammatory bowel disease when unsuspected Crohn’s disease is present or complications occur. SBS related to desmoid tumors has a poor prognosis in patients undergoing resection alone. A more aggressive approach to intestinal transplantation in these patients may be warranted.     

Safety and Efficacy of Hyperthermic Intraperitoneal Chemoperfusion with High-Dose Oxaliplatin in Patients with Peritoneal Carcinomatosis

Background Cytoreduction with hyperthermic intraperitoneal chemoperfusion (HIPEC) has an established role in selected patients with peritoneal carcinomatosis (PC). We analyzed the safety and efficacy of HIPEC using high-dose oxaliplatin, a cytotoxic agent commonly used in metastatic colorectal cancer and showing promising activity in ovarian cancer and mesothelioma. Methods Following complete cytoreduction, HIPEC was performed using 460 mg/m² oxaliplatin in 5% dextrose for 30 min at a temperature of 41–42°C. Open perfusion (coliseum technique) was performed in all patients. Metabolic, electrolyte, and hemodynamic changes were recorded during chemoperfusion as well as postoperative morbidity, mortality, late toxicity, and survival. Results From July 2005 to January 2007, 52 patients were treated. Chemoperfusion with 5% dextrose resulted in temporary significant hyperglycemia, hyponatremia, and metabolic acidosis. Major morbidity developed in 24% of patients, while 30-day mortality did not occur. One patient developed unexplained repeated episodes of hemoperitoneum. Chemoperfusion with oxaliplatin resulted in mild hepatic toxicity evidenced by persistent elevation of glutamyl transferase and alkaline phosphatase 1 month after surgery. After a mean follow-up time of 14.5 months, nine patients died from disease progression. In colorectal cancer patients, actuarial overall survival was 80% at 1 year. Conclusion Cytoreduction with HIPEC using high-dose oxaliplatin leads to manageable metabolic and electrolyte disturbances and frequent mild hepatic toxicity without discernible impact on postoperative morbidity. Longer follow-up in a larger patient cohort will be required to assess the real risk of unexplained hemoperitoneum observed in one patient, and to establish the long-term effect on local relapse and survival.     

Masked severe stenosing ureteritis: a rare complication of Henoch-Schönlein purpura

Henoch-Schönlein purpura (HSP)-associated stenosing ureteritis represents a rare complication of the disease, typically presenting with severe manifestations. This article reports on a 3.5-year-old boy with HSP and severe nephritis who developed a unilateral stenosing ureteritis with atypical manifestations, resulting in a nonfunctional kidney and consequent nephrectomy. The urinary tract ultrasound was normal in the first week of illness, and the diagnosis was made during follow-up 8 months after onset. The predominance of nephritic manifestations may have masked any signs of ureteritis, leading to the delay in diagnosis. To clarify the clinical spectrum of this complication, an extensive review of the literature was performed. We emphasize the necessity of repeated urinary tract ultrasound both early and later in the course of HSP, especially in cases with renal involvement, so that an early diagnosis of this complication can prevent a potentially serious renal outcome.     

Which cystography in the diagnosis and grading of vesicoureteral reflux?

The gold standard procedure for the evaluation of vesicoureteral reflux (VUR) is the radiographic voiding cystourethrography (VCUG); direct radionuclide voiding cystography (DRVC) is an alternative method for detecting VUR. A new imaging procedure, voiding urosonography (VUS) with contrast medium, has recently been introduced. We have carried out a comparative study of these three techniques in 157 patients (aged 6 weeks–4.7 years). VUS showed the presence of VUR in 91 of 311 renal units; VCUG detected reflux in 64 of 233 renal units, and the DRVC in 23 of 78 renal units. VCUG and VUS were compared in 118 patients, and both procedures showed the same grade of reflux in 56 refluxing units (kappa value 0.92); in six cases the reflux grade was greater at VUS than at VCUG. Seven cases of reflux detected by VUS were not identified on VCUG. VCUG did not show a grade of VUR that was higher than in VUS in any patient. In the identification of 4°–5° grade reflux, the sensitivity of VUS reached 100%. VUS and DRVC were found to be equally effective in the detection of VUR (kappa value 0.85). In conclusion, we found that VUS is a useful method for the diagnosis and grading of patients with VUR.     

The Impact of Roux Limb Length on Weight Loss After Gastric Bypass

Background Extending the length of the Roux limb (RL) in gastric bypass (GBP) may improve weight loss in super obese patients (body mass index [BMI] > 50 kg/m²), but no consensus exists about the optimal length of the RL. We sought to determine the impact of RL length on weight loss in super obese patients 1 year after GBP. Materials and Methods One-year weight loss outcomes were analyzed in all super obese patients who underwent consecutive and primary laparoscopic or open GBP between January 2003 and June 2006. Patients were divided into two groups according to RL length (100 vs. 150 cm). The RL length was at the discretion of the attending surgeon. Baseline and follow-up data were collected prospectively. Multiple linear regression was used to adjust for potential confounders in the weight loss outcomes. Results Twelve-month follow-up data were available in 137 (85%) of 161 patients with a BMI ≥ 50 who underwent GBP during the study period. An RL of 100 or 150 cm was used in 102 (74.5%) and 35 patients (25.5%), respectively. In multivariate analysis, patients with the 150-cm RL lost more weight (68.5 vs. 55.3 kg, p < 0.01), had a greater change in BMI (25 vs. 21 kg/m², p = 0.01), and had greater excess weight loss (64 vs. 53%, p < 0.01). Conclusion A 150-cm RL provides better weight loss outcomes in super obese patients at 1-year follow-up.     

Prognosis of subacute low back pain patients according to pain response

Centralization of referred pain or failure to centralize has in earlier studies been shown to be a predictor of low back pain prognosis. Research suggests that there are differences in how males and females experience pain. The aim of this study was to evaluate the outcome after 1 year, and to evaluate the prognostic value of the pain response in a mechanical test at the first consultation at a spine clinic, and the influence of gender, in order to identify patients with especially high risk of chronicity. The patients in this study were low back pain patients, included consecutively from a spine clinic in Northern Denmark. The criteria for entering this spine clinic were neck or low back pain with radiating symptoms and a duration of 4–26 weeks, without satisfactory improvement after treatment in the primary care system. The 793 patients were categorised into four subgroups according to their pain response in a mechanical test performed at the initial examination: centralization, non-lasting centralization, peripheralization and no effect. The patients were instructed in doing specific exercises according to the test results. The four subgroups were compared after 1 year with regard to changes in back and leg pain, disability and return-to-work status. The statistical evaluation was undertaken for the study group as a whole and stratified according to gender. A significant improvement in all outcome measures was found in all the subgroups, among both men and women. There were no systematic or statistically significant differences in the prognosis between the four subgroups of patients. The proportion of Centralizers in this study was 18%. The mechanical test at baseline is important for deciding the subject-specific exercises, but when treated according to test results, the prognostic value of the test seems limited. The project is approved by the Regional Scientific Ethical Committee.     

Evaluation of cystine transport in cultured human kidney cells and establishment of cystinuria type I phenotype by antisense technology

Cystinuria is a rare hereditary disease resulting in recurrent stone formation and the need for repeated invasive interventions. So far, two responsible genes have been identified which encode the two transporters, rBAT and b^0,+AT forming a heterodimer to transport cystine in proximal tubular cells (PTC) and whose defect results in increased excretion of cystine. A human cell line mimicing the phenotype of cystinuria in vitro is yet to be developed. Human kidney (HK)-2 is a PTC line derived from normal HK. After determining the presence of rBAT gene by RT-PCR and Western blot analysis, radioactively labeled cystine (S³⁵) was used to evaluate the functional presence of the amino acid transport in HK-2 cells when cultured in vitro. To achieve a cystinuria type I phenotype in HK-2 cells, the rBAT gene was silenced using antisense oligonucleotides complimentary to human rBAT mRNA. The reduced transport activity of cystine was then determined by radiolabeled cystine uptake measurements. RT-PCR and Western blot confirmed the expression of the rBAT gene in HK-2 cells. Considerable transport of the radio labeled cystine was observed in HK-2 cells and was linearly dependent on the incubation time with the amino acid. The cystine transport in rBAT knockdown cells after incubation with antisense oligonucleotides was significantly lower compared to control (0.76 vs. 0.98%; P = 0.0008), proving a transient knock-down of the rBAT gene. This study demonstrates the presence of the b^0,+ amino acid transport system in human proximal tubular HK-2 cells when cultured in vitro. Inhibition of this transport system is possible by using antisense technology. A permanent inhibition of the cystine transport, based on our model, would be useful for the development and evaluation gene therapeutic approaches. Gunnar Wendt-Nordahl, Sreedhar Sagi contributed equally to this work.