Search

Background: Systemic thrombolysis with tissue plasminogen activator (t-PA) for treatment of acute ischemic stroke was approved in Germany in 2000. Up to now, only data from single centers have been available for the study of the use of thrombolysis in a hospital-based approach outside controlled trials. We therefore sought to determine the frequency of application and complications as well as the patient outcome after t-PA treatment in clinical routine of specialized stroke centers in Germany., Methods: Within the German Stroke Data Bank Collaboration, 6234 consecutive patients with ischemic stroke were prospectively documented in 20 stroke centers between 1998 and 1999. The patients were centrally followed via telephone interview after 3 months and 1 year to assess global functional outcome using the Modified Rankin Scale., Results: 250 patients (4 %) received systemic t-PA treatment during the study period. The baseline characteristics of these patients were comparable to large clinical trials and phase IV studies. Symptomatic and asymptomatic parenchymal hemorrhage occurred in 22 patients (8.8 %) and was fatal in 3 patients. Follow-up data after 3 months were obtained in 82.4 % of all patients, of which 35 % had a favorable functional outcome (mRS /= 4) and 17 % had died., Conclusion: The results of our study agree with the assumption that thrombolytic therapy can be performed safely and effectively in daily clinical practice. Nevertheless, the small proportion of patients receiving thrombolysis even in specialized stroke centers calls for further improvement of acute stroke management in Germany.

Poly(ADP-ribosyl)ation plays important roles in cellular DNA repair mechanisms as well as in cellular proliferation and genomic stability. Four carcinoma cell lines, LNCaP, PC-3, C4-2 and MatLu, and one prostate epithelial cell line, PNT1A, were tested using the H10 antibody to poly(ADP-ribose) by Western blotting and FACS analysis for basal and activated (10 mM H2O2) PARP activity. In both analyses, higher levels of basal polymer were present in the LNCaP cell line than in the prostate epithelial cell line or the MatLu cell an line. LNCaP cells demonstrated greater than 90% positive analyzed cells in FACS analysis both before and after treatment with H2O2. PNT1A epithelial cells demonstrated evidence of polymer presence only after treatment with H2O2. Microsatellite instability due to increased oxidative damage in tumor cells has been proposed as a means for accumulation of genetic changes. As oxidative stress can stimulate poly(ADP-ribose) reactions, an increased presence of the polymer may indicate a high level of oxidative damage occurring in the tumor cells, contributing to higher levels of genetic instability towards progression.

Cystinuria, an autosomal-recessive disorder, is the cause of 1 - 2 % of all kidney stones observed in adults and about 10 % of those observed in infants. Despite increasing understanding of underlying pathomechanisms, patients still form recurrent stones and have to undergo repeated interventions with increasing risk of renal insufficiency. Dietary and medical metaphylaxis may lower the frequency of recurrent stones but are often not practiced. Regular follow-up examinations and optimal therapy significantly enlarge stone-free intervals. This review offers an overview of the underlying pathogenetic mechanisms as well as guidance for diagnosis, monitoring, metaphylaxis and therapy of cystinuria following the recommendations of the Deutsche Gesellschaft für Urologie (DGU) and the European Association of Urology (EAU).

With a prevalence of around 5% in western countries, urolithiasis is a frequently occurring disease but with a poorly understood pathogenesis. Effective prevention is not possible for most stone types, in particular for calcium-containing stones, which occur most frequently. Additionally, after occurrence, patient compliance is often inadequate. Interventional therapy becomes necessary after stone manifestation within the urinary tract. Not all stone compositions respond to a drug treatment. Whereas in the seventies, stone treatment meant open surgery newly developed minimally-invasive procedures have displaced this treatment. The clinical introduction of extracorporal shock wave lithotripsy (ESWL) has played a crucial role in this process. Today, more than 80% of all urinary stones can be treated by modern lithotripters. Combination with other minimally-invasive procedures further improve stone free rate. This article provides an overview of technique, application and results of ESWL treatment.

While calcium oxalate and calcium phosphate make up at least 80% of all kidney stones, infection-induced and uric acid stones occur in 10% and 8%, respectively. Although any type of stone may become infected, the term "infection stones" means that stone formation exclusively depends on urease-producing bacteria. The splitting of urea leads to a rise in urinary pH which may induce crystallization of struvite (magnesium-ammonium-phosphate), the major constituent of infection stones, or carbonate apatite. Struvite stones account for the majority of staghorn calculi. They can grow quite large and may fill the entire collecting system. Patients with struvite stones may present with acute flank pain or remain completely asymptomatic. The cure of infection stones requires complete removal of the stone material. For uric acid crystallization and stone formation, low urine pH (below 5.5) is a more important risk factor than increased urinary uric acid excretion. Main causes of low urine pH are tubular disorders (including gout), chronic diarrheal states or severe dehydration. Accordingly, the treatment of uric acid stones consists not only of hydration (urine volume above 2000 ml per day), but mainly of urine alkalinization to pH values between 6.2 and 6.8. Urinary uric acid excretion can be reduced by a low-purine diet as well as--in case of recurrent uric acid stones and/or gout--by allopurinol. Cystinuria is a rare hereditary gene disorders with impaired tubular reabsorption of cystine. Stone formation occurs as a consequence of cystine's relatively low solubility at urine pH levels below 8. Only symptomatic diet and drug treatments are currently available, with urine dilution and urine alkalinization being the most efficient ones. Cystine stones respond poorly to shockwave lithotripsy, so that invasive procedures may regularly be necessary. 2,8-dihydroxy-adenine stones occur as a consequence of an enzyme deficiency that involves purine metabolism. These resulting stones are not visible by fluoroscopy and are therefore often misinterpreted as uric acid stones. Low-purine diet and allopurinol reduce the frequency of stone formation.

Although ESWL allows for the treatment of most urinary stones, there are remaining situations, in which satisfying results cannot be achieved, e.g. large kidney stones or specific anatomy. In such cases endoscopic procedure like ureterorenoscopy (URS) or percutaneous nephrolithotomy (PCNL), alone or in combination with ESWL, allow minimally-invasive removal of these stones. Primarily, the development of modern intracorporeal lithotripter probes and extraction instruments along with a reduction of instruments' diameter could improve efficacy and reduce mortality. This article will provide an overview of techniques, application and results of endoscopic urinary stone treatment.

New approaches to treat prostate cancer (PCA) are utilizing gene therapy and aim to correct the disease at the genetic level. Getting a gene efficiently into the target cell is the subject of much interest. We used a holmium laser for transfecting rat PCA cells with the reporter gene pEGFP. By FACS analysis and fluorescence microscopy, we could demonstrate that cellular delivery of plasmid DNA was possible with high efficiencies up to 41.3%. Therefore, transfection of PCA cells by holmium laser might offer a promising new gene transfer strategy to PCA with minimal invasiveness.

Introduction: Besides standard open or transurethreal adenoma resection, less morbid interstitial laser coagulation (ILC) is an alternative therapeutical option that could reduce lower urinary tract symptoms, especially in high-risk patients. Although short-term results indicate effectiveness, reliable long-term statistics are still lacking. Therefore, to assess long-term satisfaction and overall success rate, we re-evaluated patients with a mean follow-up of 7 years after laser treatment., Methods: A total of 72 patients had been included in our ILC programme between 1993 and 1995. Mean age was 74 years. About 45 % of the patients had since died of other causes. In all, 23 patients were evaluated by telephone questionnaire, International Prostate Symptom Score (IPSS), Quality of Life (QoL), second surgical interventions or medical therapy. Our patient group was treated with interstitial Nd:YAG laser coagulation (mediLas fibertom). A perineal (34 %), transurethral (23 %) or combined (43 %) approach was chosen, depending on the preoperative volume of the prostate (range 40 - 100 ml; mean 59.3 ml)., Results: 68.4 % of the patients were satisfied with their current urological situation. Mean IPSS was 8.8 vs. 18.8 preoperatively mean QoL 1.5 vs. 3.3. 15.8 % had undergone conventional transurethral prostatic resection in the interim; one patient uses a urine catheter. 15.8 % receive medical treatment for lower urinary tract symptoms., Conclusions: Although the results of standard TUR or open surgery imply higher success, the long-term results of ILC demonstrate effectiveness. Further follow-up studies on a larger number of patients are advisable. The low morbidity of ILC makes this procedure an interesting alternative option in the treatment of high risk patients.

Purpose: The range of maximum bladder smooth muscle tension in the published literature varies between 1.3 and 59 N/cm (2) depending on the experimental setup. Based on own animal trials, we attempted to determine bladder wall tension during detrusor contraction in physiological and obstructed voiding and during detrusor instabilities in our patient collective., Materials and Methods: In 24 patients (mean age 56 +/- 8.4 years), bladder wall tension as detrusor force per cross sectional area of bladder tissue [in N/cm (2)] was calculated following urodynamic evaluation and ultrasound determination of bladder wall thickness. The patients were divided into 3 groups with 8 patients per group as follows: group I: patients with bladder outlet obstruction in accordance with the Abrams-Griffiths nomogramme; group II: patients with detrusor instabilities; group III: patients with normal bladder emptying., Results: Maximum bladder wall tension in group I was 9.8 +/- 3.9 N/cm (2). During bladder instabilities (group II), maximum bladder wall tension was 11.7 +/- 2.6 N/cm (2). Maximum bladder wall tension was 2.8 +/- 0.5 N/cm (2) in group III, which was significantly lower (p < 0.05, Mann-Whitney U-Test) than that of groups I and II., Conclusions: We conclude that bladder wall tension is distinctly lower in patients with normal voiding than in those with obstructed micturition or detrusor instabilities. Furthermore, our results suggest that the detrusor is not fully activated during normal voiding and is thus capable of compensating for to a greater stress situation with more effective contractions.

Elevated body temperature increases mortality and worsens outcome in acute stroke patients. In animal models of stroke, even slight hypothermia was shown to be neuroprotective. Pharmacological treatment alone (paracetamol, metamizol) usually fails to lower core body temperature below 37 degrees C. The purpose of this study was to establish the feasibility and safety of continuous body surface cooling towards low normothermic temperatures in noncomatose, nonventilated stroke unit patients. Eighteen acute stroke patients (15 ischemic infarcts, 3 hemorrhages) with baseline body core temperatures >37.0 degrees C (taken in the urinary bladder) were laid on a water-perfused cooling mattress and received pethidine and dihydroergotoxine in order to avoid shivering and peripheral vasoconstriction. The target range for core body temperature was between 36 and 37 degrees C for 24 hours. None of the patients was treated with antipyretic drugs during the cooling period. Median baseline National Institutes of Health Stroke Scale score (NIHSSS) was 15.5 (8-24). Three patients had core temperatures >38 degrees C. A temperature in the target range could be reached within 3.3 hours (median) and maintained in all but two patients. Major procedure-related adverse events were vomiting (n = 2), drop in mean arterial blood pressure >20% (n = 2), pneumonia (n = 2), and a rise in central venous pressure >20 cm H2O (n = 3) totaling 9 events in 8 of 18 patients (44%). No patient died within the first week; mortality after three months was 12%. Continuous body core temperature reduction of 1-2 degrees C may safely be attained by a cooling mattress in nonventilated stroke unit patients. Critically high temperature values can be avoided. The neuroprotective potential of this method has to be assessed in a controlled trial.

Background and Purpose: Endoscopic examinations of stone-forming kidneys show a coincidence of plaques and microliths on the surface of and within papillary epithelial tissue. These calcifications are thought to be precursors of calcium oxalate urolithiasis. We hypothesized that minimally invasive endoscopic laser ablation of microliths and necrotic cell layers enables epithelial regeneration and prevents recurrent urolithiasis. The aim of this study was to determine the most suitable laser type and dose intensity for selective superficial cell ablation., Materials and Methods: Conventional Nd:YAG (1-40 W) or Ho:YAG (0.5-3 J/single impulse) lasers were used endoscopically on an ex vivo blood-perfused porcine kidney model. Defined doses were applied to the papillary surface in the contact and noncontact modes for 10 to 30 seconds. Papillae were excised after treatment and histopathologically analyzed in continuous sections. Lesions were microscopically assessed with the aid of a Leica Quantimed computer program., Results: Depending on the time and dose, vaporization by the Nd:YAG laser caused large tissue defects and coagulation necrosis at energy levels over 5 W (contact and noncontact mode). Lower energy levels with tissue contact produced only superficial cell defects (<20 cell layers) but more extensive coagulation necrosis, whereas no histologic effects were observed at the same energy level without contact. In contrast, independent of delivered energy but dependent on time, Ho:YAG laser application caused pure tissue loss without relevant coagulation necrosis. The generation of small lesions (6-10 cell layers) without tissue contact was possible at energy levels under 2 J., Conclusions: Selective superficial papillary cell ablation is possible. Low-energy Nd:YAG treatment in the contact mode and Ho:YAG treatment in the noncontact mode led to superficial vaporization with no (Ho:YAG) or minimum (Nd:YAG) coagulation defects.

The 7.5 and 9.0 F flexible ureterorenoscopes are used widely in endourology. These scopes, along with new available tools and probes, enable intrarenal ureteroscopic access to renal stones in the lower pole. Following individual clinical experiences the infundibulopelvic angle has to be respected for the selection of different scopes, tools and probes. The aim of this study was to determine the influence of different scopes, tools and probes on the angle of the active and passive flexion of the flexible ureterorenoscope. The angles of the active and passive flexion and maximum irrigation flow of different flexible ureterorenoscope (9.0 F Wolf, 7.5 F Olympus, 7.5 F Storz) were measured repeatedly in vitro using nine different inserted tools and/or probes. In addition, the maximum allowing for easy passage of the nine different tools/probes through the channel of the scope were measured. The Olympus scope without working instrument present, allows for the greatest deflection. The flexible Lithoclast, the non-nitinol baskets, and the 365 microns laser probes significantly inhibit the deflection of all scopes. The greatest deflection with inserted working tool was possible using the Wolf and Storz scopes. Both nitinol tools as well as the 200 microns laser probe had only minimal influence on the deflection. The 200 microns laser probe reduces the irrigation flow from 50 to 28 ml/min. In contrast, the baskets reduce the irrigation flow from 50 to 2 ml/min. There are significant differences of the active and passive flexion depending on the ureterorenoscopes itself and the different tools. In order to perform a successful flexible ureterorenoscopic stone treatment in the lower pole, the inhibition of the flexion of the different scopes together with the individual infundibulopelvic angle must be respected when selecting different tools and probes.

Objective: To overcome the current disadvantages of traditional training methods for ureterorenoscopy and percutaneous nephrolitholapaxy, using the URO Mentor (Simbionix, Tel Aviv, Israel) computer-assisted simulator., Methods: The URO Mentor device for training and quality control in ureterorenoscopy was developed using virtual reality, multimedia technology and intelligent tutoring systems. The central software system features a proprietary visualization engine (the SVE) which allows real-time simulation by offering a high-level object-orientated application program interface (written in C++) available for use with either Microsoft, DirectX 7 or OpenGL as platforms. The SVE includes general procedures to allow two- (2D) and three-dimensional (3D) rendering, collision detection, collision correction, 3D morphing, 2D image manipulation, texture mapping, 'bump' mapping, video texture, X-ray rendering, special effects (blood, smoke, stone fragments and more) and reflections., Results: The system allows a complete training session on a wide range of procedures by offering different types of cases and virtual patients, and features a full representation of the endourological procedures under direct vision and by using interactive fluoroscopy with a contrast agent. The supported tools include: baskets, graspers, intracorporal lithotripters, guidewires, catheters, stents, biopsy and dilatation devices. The endourological procedures that can be performed are lithotripsy, tumour resection, treatment of strictures and obstructions, stent placement and biopsies., Conclusion: The URO Mentor introduces a new generation of mannequin equipped with a special haptic device, providing trainees with an unparalleled life-like sensation while training for diagnostic and therapeutic endourological procedures. By bringing key advances into urological simulation (e.g. with the real-time X-ray renderer) and by integrating in a single system both high-quality simulation and learning tools, the URO Mentor provides new perspectives for computer-based urological training systems and methods.

Americans with disabilities are rarely considered a distinct group of health care users in the same way as are older Americans, children, racial and ethnic minorities, and others who are perceived to have different needs and access issues. Indeed, to some extent individuals with disabilities overlap with all these groups. But they also have distinct needs with material implications for the organization, delivery, and financing of health care services. Despite the disproportionate health care needs and expenditures of many--though not all--individuals with disabilities, the mainstream health services research community has largely neglected them. This article outlines the most pressing health service research issues in addressing the health care needs of individuals with disabilities.

Endothelin (ET) is known to reduce glomerular filtration rate and renal blood flow and is a possible mediator of acute renal failure (ARF). We recently demonstrated that the administration of a very high dose of the ET(A)-receptor antagonist LU 135252 (LU) accelerates recovery from postischemic acute renal failure by an improvement of renal perfusion in a rat model. The aim of this study was to investigate whether this effect of LU is dose dependent. ARF was induced in rats by clamping both renal arteries. Serum creatinine was measured and endogenous creatinine clearance and fractional sodium excretion were calculated up to 4 days after acute ischemia. Rats were treated either with the selective ET(A)-receptor antagonist LU or with vehicle only after reperfusion. LU in doses of 0.5, 1, or 5 mg/kg per day was infused via a femoral vein using an osmotic minipump. Serum creatinine was increased approximately eightfold after induction of ARF. Creatinine clearance decreased from 4.35 +/- 0.26 ml/min before acute renal failure to 0.15 +/- 0.02, 0.54 +/- 0.1, and 1.49 +/- 0.19 ml/min on days 1, 2, and 4 after ischemia (p < 0.05). Fractional sodium excretion increased from baseline 0.77 +/- 0.05% to 7.5 +/- 1.21 % on day 1 and 8.53 +/- 1.34% on day 2 (p < 0.05). Treatment with LU improved kidney function dose relatedly. There was no significant change in creatinine clearance, but compared with controls, with doses of 0.5 mg/kg per day and 1 mg/kg per day (0.28 +/- 0.1, 0.88 +/- 0.22, and 1.93 +/- 0.24 ml/min on days 1, 2, and 4), we noted a significant increase under 5 mg/kg per day (day 1: 0.62 +/- 0.17 ml/min; day 2: 1.38 +/- 0.26 ml/min; and day 4: 2.45 +/- 0.21 ml/min; p < 0.05). Fractional sodium excretion decreased dose-relatedly to a maximally 2.48 +/- 0.58% on day 1 and 2.25 +/- 0.71 % on day 2 after treatment with the highest dose when compared with untreated control rats (p < 0.05). Our data support the hypothesis that ET plays a major role in ARF. It can be concluded from these results that recovery from ischemic ARF is significantly and dose-dependently enhanced by treatment with a selective ET(A)-receptor antagonist.

The endothelin system has been identified as having a substantial role in renal failure, both acute and chronic. Beside its well characterised haemodynamic effects, its mitogenic and pro-fibrotic properties have gained increased interest in the pathophysiology of chronic renal failure. This review outlines the role of endothelin in the pathogenesis of various renal diseases with a special focus on the potential of blocking this system with endothelin receptor antagonists. So far, most data were derived from animal models, but they provide strong evidence that endothelin receptor antagonists may represent a powerful therapeutic strategy in ameliorating the course of acute and chronic renal failure.

The Stroke Unit concept of the German Neurological Society differs from its precedents in Scandinavia or the United Kingdom. Hallmarks of the German concept are very early onset of diagnosis and treatment, continuous surveillance of vital functions by bedside monitors and specialized care by a multiprofessional team. This comparison of two Stroke Units in Minden and Munich-Harlaching, working according to the new German concept, shows broad similarities in admission intervals, diagnostic procedures, treatment modalities and short term prognosis, with an exceedingly low in-hospital mortality of 3.4-5.6% and a high proportion of patients (64-69%) leaving the hospital with Barthel scores above 70. Ongoing studies will show how this kind of Stroke Unit treatment compares to general wards.

The value of a sustained lowering of elevated blood pressure below 140/80 mmHg for primary and secondary prevention of stroke has been demonstrated in controlled studies. In contrast, active lowering of blood pressure in the acute phase of a cerebral infarction is associated with the risk of causing further damage to the brain by reducing perfusion in the region of disordered vascular autoregulation surrounding the ischemic area ("penumbra"). The recommendations of a European Consensus Conference therefore apply, that in the first three days following an acute stroke the blood pressure should be cautiously lowered only when a systolic pressure of 220 mmHg or a diastolic pressure of 120 mmHg is exceeded.

Sudden focal neurological symptoms are caused by stroke in 95%, either ischemic or hemorrhagic. Diagnosis and onset of treatment has to be rapid because the tolerance of the brain tissue to ischemia is lower than in any other tissue. First priority has stabilization of vital parameters such as maintenance of high blood pressure, rehydration, oxygen supply and correction of hyper-/hypoglycemia. Of equal importance is the prompt imaging of the brain to differentiate bleeding, complete brain infarction and early ischemic signs--only the latter permitting recanalization procedures by thrombolysis in a narrow time window of three hours. Distinct etiological diagnosis by Duplex scanning and echocardiography usually follows. This information determines the stroke subtype and the choice of secondary prevention measures.

The endothelin (ET) system may play an important role in the pathogenesis of acute renal failure (ARF). We hypothesize that the course of ARF in an ischemia-reperfusion model will be markedly attenuated by the orally active ET(A)-receptor antagonist LU 135252 (LU) because of an improvement of renal perfusion. ARF was induced in rats by clamping both renal arteries for 60 min. The study was divided into two parts. In part 1, Rats received LU orally (100 mg/kg/day) starting 1 h after induction of ARF for 14 days. Cr(s), Cl(cr) and FE(na) were measured on days 1, 6, 9, and 14 after ARF. Cr(s) was lower in the treatment group on days 1 [1.3 +/- 0.31 mg/dl (n = 9) vs. 2.7 +/- 0.46 mg/dl (n = 10); p < 0.05] and 6 [0.5 +/- 0.1 mg/dl (n = 9) vs. 1.0 +/- 0.2 mg/dl (n = 9); p < 0.05], and Cl(cr) was higher on day 1 [0.9 +/- 0.17 ml/min (n = 9) vs. 0.2 +/- 0.1 ml/min (n = 8); p < 0.05] and 6 [1.8 +/- 0.29 ml/min (n = 9) vs. 1.0 +/- 0.21 ml/min (n = 9); p < 0.05] compared with vehicle. Additionally, FE(na) was lower in treated rats on day 1 [1 +/- 0.4% (n = 9) vs. 8 +/- 3% (n = 8); p < 0.051 compared with vehicle. In part 2, ARF was induced as described. Treated animals received 10 mg/kg LU on days 0, 1, 3, 6, 9, and 14 after ARF as an i.v. bolus injection. RBF, cortex blood flow (CBF), and medulla blood flow (MBF) were measured after application of LU on the same days: LU induced an increase in RBF (day 1: 14 +/- 5.3%, n = 6, p = 0.04; day 3: 15 +/- 2.8%, n = 8; p = 0.0008; day 6: 21 +/- 5.8%, n = 6, p = 0.02; day 9: 13 +/- 4%, n = 6; p = 0.03) and CBF (day 1: 8 +/- 2.2%, n = 7, p = 0.03; day 3: 7 +/- 2.5%, n = 7; p = 0.05; day 6: 18 +/- 4.8%, n = 6, p = 0.04; day 9: 10 +/- 2.5%, n = 6; p = 0.008) up to the first 9 days. MBF did increase on days 1 (9 +/- 3.1%, n = 6; p = 0.04) and 6 (13 +/- 3.6%, n = 6; p = 0.03). Our data confirm the hypothesis that ET plays a major role in the genesis of ARF associated with ischemia-reperfusion.