Hydrogen sulfide reduces inflammation following abdominal aortic occlusion in rats.

BACKGROUND: Remote renal ischemia-reperfusion injury (IRI) following infra-renal aortic occlusion leads to acute kidney injury and systemic inflammation. Hydrogen sulfide is a mediator of IRI and can ameliorate tissue injury in many organ systems. Its role in vascular surgery has yet to be established. We assessed the role of hydrogen sulfide in a rodent model of aortic occlusion. METHODS: Wistar rats were divided into sham, control, and treatment groups (n = 6). Inflammation was assessed using a nonrecovery protocol. The infra-renal aorta was cross-clamped for 60 min and animals were reperfused for 120 min. Ten minutes before clamp release, treatment animals received hydrogen sulfide (10, 30, or 50 µg/kg) and control animals received 0.9% saline injected into the retroperitoneum. Renal injury and histology were assessed by a recovery protocol. The procedure was identical to the nonrecovery arm but with a single dose of hydrogen sulfide (30 µg/kg) and animals were recovered for 7 days. RESULTS: There was no difference in animal weight between the groups (P = 0.337). In the nonrecovery arm, there was a reduction in serum levels of tumor necrosis factor alpha in sulfide-treated animals compared with controls (909 ± 98 vs. 607 ± 159 pg/mL; P = 0.0038). There was also a reduction in myeloperoxidase-positive cells in renal tissue in the sulfide-treated animals compared with controls (8 ± 4 vs. 17 ± 9; P = 0.03). There was no difference in histological injury score or endothelin-1 levels. In the recovery arm, there was no difference in renal function, Kidney Injury Molecule-1 levels, or histological injury scores. CONCLUSION: Hydrogen sulfide has systemic and renal anti-inflammatory effects in remote IRI following aortic occlusion in rats.

Coroners and medical examiners: mutualism, commensalism or parasitism?

The Coroners and Justice Act 2009 includes provisions for reform of the certification of death and the introduction of "Medical Examiners", who will scrutinise the certification of every death that is not referred to the Coroner for investigation. When these changes are implemented, Coroners and Medical Examiners will have to work closely together. But the boundaries between the two roles are not perfectly defined. Will they work together in synergy, or will they interact unwillingly and abrasively? It is clear which approach will be best for the bereaved and for society, but it is less clear what will actually happen. Medical Examiners will be led by a new Chief Medical Examiner, and Coroners will have a Chief Coroner. But these individuals will have limited powers to oblige Coroners and Medical Examiners to collaborate. It seems inevitable that there will be large variations in practice, at least initially.

Current and future delivery of diagnostic electron microscopy in the UK: results of a national survey.

AIMS: Electron microscopy (EM) remains essential to delivering several specialist areas of diagnosis, especially the interpretation of native renal biopsies. However, there is anecdotal evidence of EM units struggling to survive, for a variety of reasons. The authors sought to obtain objective evidence of the extent and the causes of this problem. METHODS: An online survey was undertaken of Fellows of the Royal College of Pathologists who use EM in diagnosis. RESULTS: A significant number of EM units anticipate having to close and hence outsource their EM work in the coming years. Yet most existing units are working to full capacity and would be unable to take on the substantial amounts of extra work implied by other units outsourcing their needs. Equipment and staffing are identified by most EM units as the major barriers to growth and are also the main reasons cited for units facing potential closure. CONCLUSIONS: In the current financial climate it seems unlikely that units will be willing to make the large investment in equipment and staff needed to take on extra work, unless they can be reasonably confident of an acceptable financial return as a result of increased external referral rates. The case is thus made for a degree of national coordination of the future provision of this specialist service, possibly through the National Commissioning Group or the new National Commissioning Board. Without this, the future of diagnostic EM services in the UK is uncertain. Its failure would pose a threat to good patient care.

Biomarkers assessing warm ischemic injury using an isolated porcine kidney hemoreperfusion model.

Prolonged warm ischemia (WI) occurring in marginal kidney donors together with reperfusion injury determines allograft survival, in which apoptosis and inflammation play crucial roles. There is no single valid biomarker, so far, to assess the degree of kidney donor injury. To define new biomarkers for detecting initial donor ischemic injury, caspase-3, caspase-7, apoptosis, inflammation, HSP70 and renal histological changes were examined in porcine kidneys subjected to 7- 15- 25- or 40-min WI, two-hour cold storage and six-hour hemoreperfusion. Caspase-3 activity was gradually increased by prolonged reperfusion, with a decrease trend against WI time. This result was verified by raised 17 kDa active caspase-3 in postreperfusion kidneys, with elevated 12 kDa active caspase-3 and lowered precursor at seven-minute WI. Active caspase-7 was also doubled by reperfusion with decreased precursor at seven-minute WI, but declined against prolonged WI. Apoptotic cells in tubular and interstitial areas were greatly increased by reperfusion at seven-minute WI, but decreased against prolonged WI. In addition, myeloperoxidase (MPO)+ cells were dramatically increased by reperfusion and presented as a bell-shape against WI time, while HSP70 was significantly increased at 7-min WI, but decreased at 40-min WI after reperfusion. In postreperfusion kidneys, tubular dilation and cell shedding were observed at 7- and 15-min WI, while tubular vacuolation and cell debris were found in tubular lumens at longer WI times. At 40-min WI, early nuclear pyknosis, tubular epithelia detachment and peri-tubular capillary dilation were detected. Furthermore, caspase-3, caspase-7, apoptosis, but not MPO+ cells or HSP70, were correlated with renal function. In conclusion, caspase-3, caspase-7 and apoptosis appear to be better biomarkers than MPO+ cells or HSP70 for assessing warm ischemic injury in donor kidneys. Hemoreperfusion activates caspase-3 and caspase-7, promotes apoptosis of damaged cells in kidneys only with limited WI, which might be beneficial to renal structural re-modeling and functional recovery.

Identification of lesions indicating rejection in kidney transplant biopsies: tubulitis is severely under-detected by conventional microscopy.

BACKGROUND: In the current international Banff classification of kidney transplant rejection, tubulitis and intimal arteritis are regarded as the key histological features of acute rejection. Grade 1 tubulitis can sometimes be seen in biopsies that do not represent acute rejection; but in the case of intimal arteritis, just one lymphocyte can justify anti-rejection treatment. Our aim was to audit reliability and accuracy of recognizing tubulitis and intimal arteritis using the approach recommended by the Banff classification and correlate any discrepancies with subsequent graft function. METHODS: This is a retrospective review of all kidney transplant biopsies reported as negative for rejection from 1 January 2009 to 31 December 2009 to assess the presence or absence of occult tubulitis and arteritis. Lymphocytes were immunostained with CD3, using Periodic Acid Schiff as a counterstain. Sections were reviewed to detect missed intimal arteritis and tubulitis. Discrepancies between the report and the immunostain results were analysed by biopsy type and broken down by the reporting pathologist. The graft function of any patient with missed lesions was checked to test for adverse impact on the patient. RESULTS: 'Missed' tubulitis was found in 68% of biopsies, but only two such cases subsequently developed biopsy-proven acute rejection. Only one case of missed intimal arteritis was found (1%) and the subsequent clinical course suggested that this was probably early rejection. There was no significant difference between the reporting pathologists. CONCLUSIONS: We conclude that tubulitis is missed very frequently, but the Banff classification seems to be 'calibrated' to allow for this and it does not seriously affect the identification of clinically significant acute rejection. Immunostaining is therefore not indicated in routine practice because (by Banff criteria) it would result in over-diagnosis of rejection. Intimal arteritis can indicate acute rejection even if extremely mild.

Ipsilateral ureteroureterostomy in the surgical management of the severely dilated ureter in ureteral duplication.

PURPOSE: Ipsilateral ureteroureterostomy for the surgical management of severely dilated ureter in ureteral duplication is well supported in the surgical literature but often not done. We evaluated our institutional experience with ureteroureterostomy in duplication anomalies to assess the feasibility and success of this procedure. MATERIALS AND METHODS: An 8-year retrospective review of the records of all patients with complete renal duplex anomalies was evaluated. Anatomical presentations, and operative and nonoperative treatment of these patients were evaluated. RESULTS: A total of 193 patients were identified with complete renal duplication. Associated anomalies included ureterocele in 24 patients, ectopic ureter in 38 and vesicoureteral reflux in 57. Of 193 patients 160 (83%) with duplex anomalies underwent surgical intervention with a total of 41 ureteroureterostomies performed in 39 patients with dilated donor ureters. A total of 11 ureteroureterostomies were performed primarily and 30 were performed in conjunction with ipsilateral ureteral reimplantation of the distal common segment below the ureteroureterostomy. Ten of the 39 patients had the contralateral side reimplanted for vesicoureteral reflux. In all children with ureteroureterostomy the anastomosis between the 2 ureters remained patent. Two of the 11 children who underwent ureteroureterostomy alone had de novo ipsilateral vesicoureteral reflux (1), which was treated with ureteral reimplantation, and subureteral injection (1). Two children who underwent concomitant ureteroureterostomy and reimplantation without indwelling stents had transient postoperative urinomas that required subsequent drainage. Additionally, 3 patients had persistent ipsilateral vesicoureteral reflux, which was treated with subureteral injection in 1 and observation in 2. One patient presented with transient ipsilateral urinary obstruction, which required percutaneous drainage and resolved spontaneously. CONCLUSIONS: In cases of ureteral duplication with a severely dilated ureter requiring surgical intervention ipsilateral ureteroureterostomy is a viable option for reflux and/or obstruction. The procedure is rapid and technically feasible, and it offers excellent cosmesis. In addition, ureteroureterostomy has minimal morbidity and it facilitates early hospital discharge.

Minimally invasive open renal surgery.

PURPOSE: Improved pediatric laparoscopic techniques and instruments have led to the increased popularity of laparoscopic pyeloplasty and nephrectomy at some centers. The recent trend has compared laparoscopic to open techniques to draw parallel conclusions from the adult literature that laparoscopic surgery in children offers the same advantages. Historically open renal surgery in the pediatric population has been done successfully but usually through more traumatic incisions. We present our experience with minimally invasive open renal surgery. MATERIALS AND METHODS: A retrospective review of the last 6 years was performed of consecutive open pyeloplasties for ureteropelvic junction obstruction and open nephrectomy for multicystic dysplastic kidneys and renal duplication anomalies at a tertiary hospital for children. Parameters evaluated were patient age at surgery, surgical incision size, operative time, hospital stay and the need for postoperative narcotics. RESULTS: A total of 135 patients underwent open renal surgery using an open retroperitoneal flank incision, including 66 younger than 1, 32 who were 1 to 5, 11 who were 5 to 10 and 26 who were older than 10 years. Mean +/- SD operative time was 101.4 +/- 44.7 minutes in patients younger than 1 year, 87.7 +/- 39.3 minutes in those 1 to 5 years old, 127.1 +/- 62.7 minutes in those 5 to 10 years old and 127.8 +/- 38.4 minutes in those older than 10 years. Incision size for the groups was 1.9 +/- 0.61, 1.9 +/- 0.72, 3.0 +/- 1.3 and 3.8 +/- 1.6 cm, respectively. The last 20 patients younger than 1 year who underwent open pyeloplasty had an incision of between 1 and 1.5 cm. Most incisions were performed through a posterior, subcostal muscle splitting approach. All patients received postoperative ketorolac. Supplemental narcotics were not required in any patients younger than 10 years. Of the patients 90% were discharged home in less than 23 hours. CONCLUSIONS: The minimally invasive approach to open renal surgery is a safe and effective treatment choice in pediatric urology. The procedure can be easily performed through a small incision with minimal morbidity, comparable operative time and excellent cosmesis without excessive postoperative pain issues, allowing early discharge home. Perhaps this refined open surgery technique should be the benchmark for comparing new techniques.

Teratoid Wilms' tumor, an important variant of nephroblastoma.

PURPOSE: The teratoid histologic variant of Wilms' tumor is rare, with only 15 prior reported cases. We review these and report an additional case in which a cytogenetic abnormality was identified that has not previously been reported in a teratoid Wilms' tumor. MATERIALS AND METHODS: A medline search revealed 15 previously reported cases of the teratoid variant of Wilms' tumor. We summarized the characteristics of these cases with attention to radiologic appearance, stage, laterality, histology, response to chemotherapy and outcomes. RESULTS: Characteristic radiologic features suggesting teratoid Wilms' tumor were calcific densities and stippling, or areas of attenuation indicating adipose tissue. The majority of teratoid Wilms' tumor patients had a high tumor stage at presentation (50% stage III or greater). The incidence of bilateral tumors was 38%. Chemotherapy was administered in nine cases and in only one (11%) was there a cytoreductive response. Four deaths (25%) occurred amongst these patients. CONCLUSIONS: Teratoid Wilms' tumors appear to present with a high stage, increased incidence of bilaterality and have a high mortality rate. Treatment strategies should focus on total surgical extirpation, including metastatic sites when feasible, due to this entity's limited response to chemotherapy.

Betamethasone cream for the treatment of pre-pubertal labial adhesions.

PURPOSE: We evaluated the efficacy of 0.05% betamethasone cream for the treatment of pre-pubertal labial adhesions. METHODS: We retrospectively reviewed the records of 19 children with labial adhesions who were treated with betamethasone cream from 6/2001 to 3/2003. Children were treated with 1 to 3 courses of twice-daily 0.05% betamethasone cream for 4 to 6 weeks. Successful lysis of adhesions was assessed by clinical exam or parental phone contact and outcomes were defined as: (1) success--complete separation of labia, (2) partial success--greater than 75% separation, (3) progression to surgical lysis, and (4) lost to follow-up. RESULTS: Nineteen patients with an average age of 58 months (range 12 to 132 months) were treated. Four of the 19 patients had never been treated previously and 1 had been treated previously with surgical lysis of adhesions only. Fourteen of the 19 patients had been previously treated with conjugated estrogen (Premarin) cream. Two of these fourteen patients had also undergone surgical lysis of adhesions. Severity of adhesions ranged from 33% to 99% labial closure. Betamethasone cream was successful in treating 13/19 (68%) pre-pubertal labial adhesions. Eleven (85%) of these 13 patients had complete resolution of labial adhesions with 1 course of treatment, 1 (7.5%) had resolution with 2 courses of treatment and 1 (7.5%) had resolution with 3 courses of treatment. One patient had a partial success with 3 courses of betamethasone cream. Two (11%) patients underwent surgical lysis of adhesion after 1 and 2 courses of betamethasone cream respectively. Three (16%) patients were lost to follow-up. Average follow-up was 7 months (range 1-24 months). No adverse outcomes or untoward effects were noted in any of the patients treated. CONCLUSIONS: Betamethasone 0.05% cream appears to be a safe and effective treatment of pre-pubertal labial adhesions as primary therapy or in patients that have failed previous therapies and it may avoid the undesirable side effects of breast budding and hyperpigmentation that can be associated with Estrogen creams.