Misoprostol Partially Inhibits the Renal Scarring of Chronic Cyclosporine Nephrotoxicity

Chronic cyclosporine (CY) nephrotoxicity is a well-known complication of this immunosuppressive agent, which may, in part, be attributed to abnormalities in renal prostaglandin content. We utilized misoprostol (M), a prostaglandin E(1) analog, in a rat model of chronic CY toxicity at 7 and 28 days to determine effectiveness in prevention of the renal damage. After 7 days, there were no differences in weight change, creatinine clearance, or renal scarring in rats treated with vehicle (V), CY, or CY + M; however, renal procollagen alpha 1(I) mRNA levels were increased in CY versus V rats (p < 0.05). In contrast, after 28 days CY rats had significant reductions in weight gain, glomerular filtration rate, and renal blood flow with increases in renal scarring and procollagen alpha 1 (IV) mRNA levels (all p < 0.05 versus V). Addition of M resulted in partial but significant improvement in GFR, RBF, and procollagen alpha 1(IV) mRNA levels, with lessening of the renal scarring. Skin fibroblasts also were incubated with CY and M to assess impact on procollagen MRNA levels. CY augmented fibroblast procollagen mRNA levels which enhanced by a large dose of M, but inhibited with a moderate dose. These data suggest that M improves renal scarring induced by CY by hemodynamic and/or direct effects.     

Lessons learned from four advanced abdominal pregnancies at an East African Health Center

AIMS: To analyze diagnosis and treatment of four advanced abdominal pregnancies in a low-resource setting of a developing country. METHODS: Extrauterine pregnancies occurring between 1997 and 2003 were identified from hospital records of the Mikumi Health Center in Tanzania/East Africa. RESULTS: A total of 45 extrauterine pregnancies were diagnosed four of which were advanced and located in the abdominal cavity. At the time of diagnosis, pregnancies were at 33, 34, 36 and 39 weeks of gestation, respectively. All four mothers survived but three of four fetuses died. One child is alive and well three years after delivery. CONCLUSION: Abdominal pregnancy is rather difficult to detect in a low-resource setting of a developing country. Persistent abdominal pain and tenderness, as well as fetal movements in the upper abdomen associated with abnormal fetal lie, may lead to its diagnosis. Localizing the fetal heart sounds in the maternal epigastrium especially in patients with abdominal pain may also be helpful in diagnosing an abdominal pregnancy. In addition, the lack of cervical changes or a displaced cervix should lead to the suspicion of an abdominal pregnancy.     

Elective percutaneous dilatational tracheostomy. A new simple bedside procedure; preliminary report

The development by the senior author (P.C.) of percutaneous tracheostomy from cricothyroidostomy and subcricoid fingertip tracheostomy is traced, and the technique and patient material of percutaneous subcricoid tracheostomy is presented. This new technique consists of inserting a tracheostomy tube by the use of a J guide wire inserted through a cannula into the tracheal lumen. Tapered dilators follow the guide wire and dilate the opening in the tracheal walls. A tracheostomy tube snugly fitted over a dilator is then passed into the trachea between the cricoid cartilage and the first tracheal ring. This procedure avoids the immediate and postoperative complications of "standard" tracheostomy. An experience of 134 tracheostomies of various types culminated in the development of the percutaneous technique. To date 26 such operations on 24 patients have been done with no significant complications due to the operation. The percutaneous technique should reduce the severity and incidence of intraoperative complications. Late complications, which have been no problem to date, are being evaluated with longer follow-up and with a greater patient population.     

EAU Guidelines on vesicoureteral reflux in children

Context

Primary vesicoureteral reflux (VUR) is a common congenital urinary tract abnormality in children. There is considerable controversy regarding its management. Preservation of kidney function is the main goal of treatment, which necessitates identification of patients requiring early intervention.

Objective

To present a management approach for VUR based on early risk assessment.

Evidence acquisition

A literature search was performed and the data reviewed. From selected papers, data were extracted and analyzed with a focus on risk stratification. The authors recognize that there are limited high-level data on which to base unequivocal recommendations, necessitating a revisiting of this topic in the years to come.

Evidence synthesis

There is no consensus on the optimal management of VUR or on its diagnostic procedures, treatment options, or most effective timing of treatment. By defining risk factors (family history, gender, laterality, age at presentation, presenting symptoms, VUR grade, duplication, and other voiding dysfunctions), early stratification should allow identification of patients at high potential risk of renal scarring and urinary tract infections (UTIs). Imaging is the basis for diagnosis and further management. Standard imaging tests comprise renal and bladder ultrasonography, voiding cystourethrography, and nuclear renal scanning. There is a well-documented link with lower urinary tract dysfunction (LUTD); patients with LUTD and febrile UTI are likely to present with VUR. Diagnosis can be confirmed through a video urodynamic study combined with a urodynamic investigation. Early screening of the siblings and offspring of reflux patients seems indicated.Conservative therapy includes watchful waiting, intermittent or continuous antibiotic prophylaxis, and bladder rehabilitation in patients with LUTD. The goal of the conservative approach is prevention of febrile UTI, since VUR will not damage the kidney when it is free of infection. Interventional therapies include injection of bulking agents and ureteral reimplantation. Reimplantation can be performed using a number of different surgical approaches, with a recent focus on minimally invasive techniques.

Conclusions

While it is important to avoid overtreatment, finding a balance between cases with clinically insignificant VUR and cases that require immediate intervention should be the guiding principle in the management of children presenting with VUR.     

A novel bioartificial liver with culture of porcine hepatocyte aggregates under simulated microgravity

An extracorporeal bioartificial liver device could provide vital support to patients suffering from acute liver failure. We designed a novel, customized bioreactor for use as a bioartificial liver (patent pending). The Innsbruck Bioartificial Liver (IBAL) contains aggregates of porcine hepatocytes grown under simulated microgravity. The culture vessel rotates around its longitudinal axis and is perfused by two independent circuits. The circuit responsible for exchange of plasma components with the patient consists of a dialysis tube winding spirally around the internal wall of the culture vessel. IBAL was evaluated in vitro. Viability tests showed sufficient viability of hepatocytes for up to 10 days. Cytologic examination of samples from the bioreactor showed liver cell aggregates. These were also examined by electron microscopy. A number of biochemical parameters were analyzed. In conclusion, cell culture is possible for at least 10 days in the IBAL system, organoid hepatocyte aggregates are formed and synthetic activity of the hepatocytes was demonstrated.     

Changes of cerebral blood flow during the secondary expansion of a cortical contusion assessed by 14C-iodoantipyrine autoradiography in mice using a non-invasive protocol

Although changes of cerebral blood flow (CBF) in and around traumatic contusions are well documented, the role of CBF for the delayed death of neuronal cells in the traumatic penumbra ultimately resulting in secondary contusion expansion remains unclear. The aim of the current study was therefore to investigate the relationship between changes of CBF and progressive peri-contusional cell death following traumatic brain injury (TBI). CBF and contusion size were measured in C57Bl6 mice under continuous on-line monitoring of (ETp)CO2 before, and at 15 min and 24 h following controlled cortical impact by 14C-iodoantipyrine autoradiography (IAP-AR; n = 5-6 per group) and by Nissl staining, respectively. Contused and ischemic (CBF < 10%) tissue volumes were calculated and compared over time. Cortical CBF in not injured mice varied between 69 and 93 mL/100mg/min depending on the anatomical location. Fifteen minutes after trauma, CBF decreased in the whole brain by approximately 50% (39 +/- 18 mL/100mg/min; p < 0.05), except in contused tissue where it fell by more than 90% (3 +/- 2 mL/100mg/min; p < 0.001). Within 24 h after TBI, CBF recovered to normal values in all brain areas except the contusion where it remained reduced by more than 90% (p < 0.001). Contusion volume expanded from 24.9 to 35.5 mm3 (p < 0.01) from 15 min to 24 h after trauma (+43%), whereas the area of severe ischemia (CBF < 10%) showed only a minimal (+13%) and not significant increase (22.3 to 25.1 mm3). The current data therefore suggest that the delayed secondary expansion of a cortical contusion following traumatic brain injury may not be caused by a reduction of CBF alone.     

Endoluminal stent graft repair for acute and chronic type B aortic dissection and atherosclerotic aneurysm of the thoracic aorta: an interdisciplinary task

Objective: Endoluminal thoracic aortic stenting is a new therapeutic tool in reducing the operative trauma of the patient. However, the inherent risks of aortic stent grafting are perivascular leakage, stent dislocation, blunt rupture of the aorta, side branch occlusion and neurological sequelae. To reduce these risks, in our institution all stent implantations were performed in close collaboration with our fellow cardiologists under biplane X-ray control supported by simultaneous intravascular and transoesophageal ultrasound imaging. Methods: Between August 1999 and August 2001, endovascular stent graft repair was performed in 34 patients (27 male, seven female) with a mean age of 68.6±7 years (range 58–84). Indication for treatment was an acute Type B aortic dissection in six patients (18%), a symptomatic chronic Type B dissection in 12 patients (35%), a true aneurysm of the descending aorta in seven patients (21%) and an atherosclerotic contained rupture of the descending aorta in nine (26%) patients. Out of six acute type B dissections three patients (8.8%) and one patient (2.9%) out of the chronic dissection group were in severe haemorrhagic shock, ventilated and required high-dose adrenergic support. The others (30 patients, 88.3%) remained symptomatic despite maximum medical treatment. In a special case a combined surgical and endoluminal stent graft repair was performed. Individually manufactured Talent, Medtronic AVE (33), and Gore (1) stents were used. Follow-up examination was performed 1 week after implantation and repeated every 3 months (mean follow-up 8 months, range 1–24). Results: In all patients the aneurysm or the entry of the dissection could be excluded. The observed hospital mortality was 2.9% (one patient). No perivascular leakage, no stent dislocation, no neurological deficit or perfusion impairment was observed. All patients except four were extubated immediately after the procedure and discharged from hospital on postoperative day 2–3. The late procedure-related mortality was 5.8% (two patients) resulting in an overall mortality of 8.8% (three patients). Conclusion: Stent graft repair is a safe and feasible treatment option for selected patients, especially in emergency situations, if the aortic lesions can be clearly identified and localized. The use of biplane X-ray control combined with simultaneous intravascular and transoesophageal ultrasound imaging in an interdisciplinary approach enables a more precise targeting of the stent landing zone, resulting in low morbidity and mortality rates.     

Second report (1998-2006) of the International Registry of Hand and Composite Tissue Transplantation

Since May 2002 all groups performing hand transplantations have supplied detailed information to the International Registry on Hand and Composite Tissue Transplantation. This report provides a review of all hand transplants performed to date. From September 1998 to February 2006 eighteen male patients underwent 24 hand/forearm/digit transplantations (eleven unilateral and four bilateral hand transplantations, two bilateral forearm transplantations, one thumb transplantation). The level of amputation was mostly at the distal forearm or wrist. Patient average age was 32. Time since hand loss ranged from 2 months to 22 years. Immunosuppressive therapy included tacrolimus, mycophenolate mofetil, rapamycin and steroids; polyclonal or monoclonal antibodies were used for induction. Topical immunosuppression was administered in some patients. Follow-up period ranged from 34 to 85 months. Patient survival was 100%. Graft survival was 100% at 1 and 2 years. Two cases of graft failure at a later date occurred and were caused by severe inflammation and progressive rejection in a non-compliant patient. In addition, 6 hands were lost due to a rejection process as the Chinese recipients did not take their immunosuppressive treatment. These failures were communicated in January 2006. Acute rejection episodes occurred in 12 patients within the first year. Rejection was completely reversible in all compliant patients. Side-effects included opportunistic infections and metabolic complications. No life-threatening complications or malignancies were reported. As it would have been very difficult to analyse transplantation functional results in a standardized way, the Registry has performed a functional score system. All patients had achieved protective sensation and in 17 of them also discriminative sensation. Extrinsic and intrinsic muscle recovery enabled patients to perform most daily activities and 90% of the recipients returned to work, and improved manual skills allowed them not only to resume their previous jobs but also, in some cases, to find more suitable employment. Fifteen recipients reported an improvement of their quality of life and we evaluated as a very important point as patient satisfaction and well-being are mandatory goals of hand transplantation.