[Processing of medical products in the urological practice]. / Aufbereitung von Medizinprodukten in der urologischen Praxis.

The reprocessing of medical products is an important topic both in urological practices and in hospitals. The complexity is caused by the increasing variety of medical instruments and also by the increasing demands on the legally required quality of the reprocessing. The Robert Koch Institute (RKI) and the Federal Institute for Drugs and Medical Devices (BfArM) have published recommendations for the processing of MD and last updated them in 2012. This article summarizes the legal framework for the reprocessing of medical devices, how medical devices are categorized before the appropriate procedure for reprocessing can be selected and the various steps in the reprocessing. A special focus is placed on medical products that are typically found in urological practices or outpatient departments and are processed there. Furthermore, the necessity of validating the processing method and the required training (expertise) of the personnel are discussed.

[Safety and efficacy of en bloc vs. conventional transurethral resection of bladder tumors: a meta-analysis and systematic review]. / Sicherheit und Effizienz der en bloc vs. konventionellen transurethralen Resektion von Blasentumoren: eine Metaanalyse und systematic Review.

BACKGROUND: En bloc tumor resection of bladder tumors (ERBT) is a novel alternative procedure to conventional resection of bladder tumor (cTURBT), which might help to address common problems of the standard method, such as inadequate detrusor muscle in specimens, high re-resection rates and high recurrence rates. OBJECTIVE: To analyze current data on ERBT in efficacy and safety compared to cTURBT. DATA SOURCES: PubMed. STUDY SELECTION: Two independent authors identified trials based on keywords and inclusion criteria. A third author was consulted in case of discrepancies. Screening keywords: ERBT, en bloc transurethral resection of bladder tumor, TURBT en bloc. A meta-analysis of 13 studies was performed. The effect size was estimated based on odds ratios and mean differences including their corresponding two-sided 95% confidence intervals. DATA SYNTHESIS: The analyzed studies comprised a homogenous collective in terms of tumor size, tumor multiplicity and tumor stage. Operation time did not significantly differ between the methods. Differences were observed in hospitalization and catheterization time in favor of ERBT. Reported complications did not show clear differences. There was significantly more detrusor muscle in the specimens in the ERBT group. No significant differences were found in recurrence up to 2 years of follow-up. CONCLUSION: ERBT is a safe alternative to conventional TURBT with promising features regarding effective resection of detrusor muscle. More standardized data on recurrence rates, different resection modalities and resection margin results are needed.

[Navigation systems for the percutaneous access to the kidney]. / Navigierter perkutaner Zugang zur Niere.

BACKGROUND: Percutaneous access to the renal pelvis still remains the most difficult step before nephrolitholapaxy (PCNL). New imaging techniques, such as 3D imaging and various navigation instruments such as electromagnetic, sonographic, CT-controlled and marker-based/iPAD try to simplify this step and reduce complications. OBJECTIVES: In this review, various new techniques for puncturing the renal collecting system are presented and their advantages and disadvantages are evaluated. MATERIALS AND METHODS: A systematic literature search was carried out in MEDLINE, whereby only puncture techniques that have already been evaluated in clinical studies were included. RESULTS: Five different navigation methods for puncturing the renal pelvis before PCNL were found. CONCLUSION: Intraoperative navigation can be useful when puncturing the collecting system. The combination of ultrasound and fluoroscopy currently remains the gold standard. However, there is still a need for further, primarily clinical, prospective studies to determine which new imaging technology and navigation systems will prevail and thus facilitate the access route to the kidney, especially in the case of special anatomical conditions.

Testicular torsion in geriatric 82-year old man.

The leading cause of scrotal pain in the geriatric population is epididymitis. Testicular torsion is rare in adult men. This case report of an 82-year old man with acute scrotum represents the second oldest patient reported in published studies. Due to the long delay between the onset of clinical symptoms and surgical exploration, the testicular infarction with necrosis and orchiectomy ultimately occurred. The diagnosis of testicular torsion in the geriatric population is often delayed and lacks awareness for the diagnosis.

iPad-assisted percutaneous nephrolithotomy (PCNL): a matched pair analysis compared to standard PCNL.

PURPOSE: To compare iPad-assisted (Apple Inc., Cupertino, USA) percutaneous access to the kidney to the standard puncturing technique for percutaneous nephrolithotomy (PCNL). METHODS: For the iPad-assisted PCNL, a computed tomography is performed prior to surgery, using fiducial radiopaque markers. The important anatomical structures (i.e. kidney, stones) are segmented using specific software enabling the superimposition of images semi-transparently on the iPad by marker-based navigation. Twenty-two patients underwent an iPad-assisted percutaneous puncture of the kidney for PCNL. Twenty-two patients of the clinical database from the Urological Department SLK Hospital Heilbronn, who underwent the standard puncturing technique, were matched to these patients. Matching criteria were age, gender, stone volume, body mass index, stone site and the absence of anatomical variation. Puncture time, radiation exposure and number of attempts for a successful puncture were evaluated. All procedures were performed by two experienced urologists. The standard puncturing method consisted of a combination of ultrasound and fluoroscopy guidance. Chi-square and t test were used to ensure that there was no difference in the matching criteria between the groups. To compare the two methods, U test, Kruskal-Wallis and Chi-square test were used. RESULTS: Examination of radiation exposure showed a significant difference between the two groups in favour of the standard puncturing method (p < 0.01) and puncture time (p = 0.01). However, there was no significant difference in puncturing attempts (p = 0.45). CONCLUSION: The iPad-assisted navigation, with the objective being to puncture the renal collecting system, represents a new technique (IDEAL criteria 2b), which proved to be applicable in clinical practice, but still has potential for technical improvement.

[Endoscopic enucleation of the prostate]. / Endoskopische Enukleation der Prostata.

The spectrum of surgical procedures for the minimally invasive treatment of benign prostatic hyperplasia (BPH) has significantly increased over the last two decades. The simple suprapubic prostatectomy (subtotal prostatectomy, SP) has largely lost relevance in current practice. On the other hand, transurethral resection of the prostate (TURP) has been further standardized and potentially made safer by the introduction of the bipolar technique and low-pressure systems.Transurethral (endoscopic) enucleation techniques (endoscopic enucleation of the prostate, EEP) are increasingly competing with the current gold standard TURP and are replacing SP for treatment of larger adenomas. This approach is especially related to the rapid development of laser technology, which has sustainably changed the face of modern BPH treatment in a similar way to stone therapy. This has been incorporated in the clinical patient management, clinical studies and standardization of numerous surgical techniques that are systematically described in this article. Additionally, efforts have also been made to use other energy sources, such as bipolar current in EEP. With respect to scientific objectivity, high-quality clinical trials are regularly published which further strengthen the position of EEP.

[Biopsy techniques in the upper urinary tract for the diagnosis of urothelial carcinoma: systematic review]. / Biopsietechniken im oberen Harntrakt zur Diagnostik des Urothelkarzinoms: systematische Übersicht.

BACKGROUND: The diagnostic accuracy of ureteroscopic biopsies in the upper urinary tract is limited by technical difficulties during extraction and small sample size. OBJECTIVES: To evaluate the impact of different techniques and instruments on the histopathologic quality and diagnostic yield of extracted samples as well as the predictive value of clinical grading and staging on final pathologic stage at radical nephroureterectomy. MATERIALS AND METHODS: For this systematic review, we searched PubMed and Embase databases for original publications and meeting abstracts according to the PRISMA guidelines. RESULTS: Overall, we included 23 studies which comprised a total of 1547 biopsies for the investigation of diagnostic yield and 778 patients for the assessment of grade and stage concordance. We found that the median diagnostic yields of big retrograde 2F [french] forceps, antegrade 3F forceps and baskets in combination with forceps were 92% (range 83-100), 72% (50-90) and 91% (78-94), respectively. Median rates of grade concordance and upgrading across all techniques ranged between 78-89% and 5-16%, respectively, without relevant differences. CONCLUSIONS: The choice of biopsy technique affects the ability to diagnose upper tract urothelial carcinoma. The correct determination of pathologic grading is comparable between different techniques. The combination of biopsy forceps and baskets during ureterorenoscopy seems to achieve optimal diagnostic accuracy.

[Surgical positioning techniques in urology : Tips and tricks]. / Lagerungstechniken in der Urologie : Tipps und Tricks.

Correct positioning of patients during preoperative preparations is essential for success of the intervention to avoid any positioning trauma and to provide the best access to the targeted structures. The appropriate positioning (and optimal performance) means that complications are avoided and also makes an essential contribution to the smooth course of the surgical intervention. A correct position is essential particularly in urology because the organs assigned to the discipline of urology are anatomically mostly difficult to reach. A further important function of the correct positioning technique is the avoidance of injuries to the patient. This article summarizes the most common positioning techniques in urological interventions with special emphasis on the explanation of practical advice, helpful tips and possible complications that can enable even junior surgeons to correctly perform the appropriate positioning technique.

Andropogon bicornis (Poales, Poaceae): a hibernation site for Pentatomoidea (Hemiptera: Heteroptera) in a rice-growing region of Southern Brazil.

Tussocks of Andropogon bicornis (Poaceae) make up a significant part of the landscape of the rice-growing region of south Brazil. However, little is known about their role in maintaining insect diversity in anthropized regions. We tested the hypothesis that A. bicornis is a hibernation site for Pentatomoidea (Hemiptera: Heteroptera) by analyzing the composition, structure, and diversity of pentatomoid assemblages over the course of a year. A total of 208 tussocks were removed at fortnightly intervals from April 2010 to March 2011. We collected 3,423 pentatomoid specimens belonging to 22 species distributed in 13 genera of three families, Pentatomidae, Scutelleridae, and Thyreocoridae. The most common species was Tibraca limbativentris Stål, the main rice pest in southern Brazil, followed by Oebalus ypsilongriseus (De Geer) and Edessa meditabunda (Fabricius). Abundance and species richness were the lowest in January, February, and March and the highest in July, August, and September. A combination of high species diversity observed during the colder months, including several unrelated to rice, and the absence of immature specimens in the tussocks strengthens the hypothesis that A. bicornis is a hibernation site for pentatomoids in the region.

Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone.

Iloperidone, [1-[4-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]eth anone, 1, is currently undergoing clinical trials as a potential antipsychotic agent. The metabolism of iloperidone was studied in human liver microsomes to define the metabolic pathways and to identify the cytochrome P450 (CYP) isoforms responsible for the formation of major iloperidone metabolites. Iloperidone was extensively metabolized in vitro via hydroxylation, reduction and O-demethylation to produce 1-[4-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]-2- hydrox yethanone, 4; 4-[3-[4-(6-fluoro-1, 2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-alpha-met hylben zene methanol, 3, and 1-[4-[3-[4-(6-fluoro-1, 2-benzisoxazol3-yl)-1-piperidinyl]propoxy]-3-hydroxyphenyl]etha none, 2, respectively, in decreasing order of abundance. The major in vitro metabolite, 4, present in trace quantities in urine, was postulated to be either eliminated in bile as a conjugate or further metabolized to a phenol, 4-[3-[4-(6-fluoro-1, 2-benzoisoxazol-3-yl)-piperidin1-yl]propoxy]-3-methoxyphenol , 5. The formation of the three major in vitro metabolites 2, 3 and 4 was NADPH dependent. The major circulating and urinary metabolite in humans dosed with 1 was metabolite 3. The mean apparent Km and Vmax for formation of 2 by human liver microsomes was 7.4 +/- 3.0 microM and 0.0343 +/- 0.0134 nmol min-1 mg-1, respectively. The mean apparent Km and Vmax for 3 was 101.2 +/- 34.7 microM and 0.1414 +/- 0.0346 nmol min-1 mg-1, respectively. The mean apparent Km and Vmax for 4 was 39.7 +/- 10.8 microM and 0.1372 +/- 0.056 nmol min-1 mg-1, respectively. The CYP isoenzymes responsible for the formation of metabolites 2, 3 and 4 were determined by using selective chemical inhibitors and by correlation studies. Metabolites 2 and 4 were formed by CYP3A4 and by the polymorphic CYP2D6 respectively. Metabolite 3 is postulated to be produced mainly by a cytosolic enzyme(s), although CYP3A, CYP1A2 and CYP2E1 isozymes were shown to be involved in its formation as well. The power of liquid chromatography/mass spectrometry in greatly accelerating the process of identifying the human liver CYP isoforms involved in the metabolism of iloperidone was demonstrated in this study. Liquid chromatography/mass spectrometry was used in the initial studies to confirm the identities of the metabolites. This was followed by accurate and reliable quantitation of individual metabolites present in biological extracts by operating the mass spectrometer in the selected ion monitoring mode.

Synthesis and structure-activity relationships of N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine) and related analogs as potential therapeutic agents for Alzheimer's disease.

A series of novel N-(4-pyridinyl)-1H-indol-1-amines and other heteroaryl analogs was synthesized and evaluated in tests to determine potential utility for the treatment of Alzheimer's disease. From these compounds, N-propyl-N-(4-pyridinyl)-1H-indol-1-amine (besipirdine, 4c) was selected for clinical development based on in-depth biological evaluation. In addition to cholinomimetic properties based initially on in vitro inhibition of [3H]quinuclidinyl benzilate binding, in vivo reversal of scopolamine-induced behavioral deficits, and subsequently on other results, 4c also displayed enhancement of adrenergic mechanisms as evidenced in vitro by inhibition of [3H] clonidine binding and synaptosomal biogenic amine uptake, and in vivo by reversal of tetrabenazine-induced ptosis. The synthesis, structure-activity relationships for this series, and the biological profile of 4c are reported.

Substituted (pyrroloamino)pyridines: potential agents for the treatment of Alzheimer's disease.

A novel series of substituted (pyrroloamino)pyridines was synthesized, and the compounds were evaluated for cholinomimetic-like properties in vitro (inhibition of [3H]quinuclidinyl benzilate binding) and in vivo (reversal of scopolamine-induced dementia) as potential agents for the treatment of Alzheimer's disease. Compounds displaying significant activity were more broadly evaluated, which revealed the presence of a desirable adrenergic component of activity. The synthesis and structure-activity relationships for this series is presented, along with the biological profiles of selected compounds.

Besipirdine (HP 749) reduces schedule-induced polydipsia in rats.

The aim of the present paper is to report on the adrenergic and serotonergic effects of besipirdine (HP 749) in vivo and to discuss its potential use in the treatment of obsessive compulsive disorder. Besipirdine inhibited biogenic amine uptake in vitro. It prevented tetrabenazine-induced ptosis in mice and potentiated the 5-hydroxytryptophan-induced serotonin syndrome in rats. Furthermore, it decreased schedule-induced polydipsic behavior in rats. Schedule-induced polydipsia may be a model for obsessive compulsive disorder. Previous results from our group have shown that certain selective serotonin reuptake inhibitors decrease schedule-induced polydipsia after 14-21 days of treatment. Besipirdine reduced schedule-induced polydipsic behavior immediately and this reduction lasted throughout the duration of the experiment (29 days).

Selection of oligoclonal V beta-specific T cells in the intradermal response to Kveim-Siltzbach reagent in individuals with sarcoidosis.

Sarcoidosis is a multiorgan granulomatous disorder of unknown etiology characterized by noncaseating granulomas in involved tissues. A positive Kveim-Siltzbach reaction is a granulomatous response to an intradermal injection of a suspension of sarcoid tissue extract in individuals with sarcoidosis. The protracted time course and granulomatous features of this reaction have a striking resemblance to the Mitsuda reaction in tuberculous leprosy, which suggests that the Kveim-Siltzbach reaction is a response to an unknown Ag(s). To evaluate whether this reaction is Ag-driven, an analysis of the TCR V beta repertoire in 15 Kveim-Siltzbach reaction sites was performed using a PCR technique and primers specific for 20 V beta gene families. Results of this analysis demonstrated a pattern of V beta expression dominated by expression of V beta 2, V beta 3, V beta 6, or V beta 8 to levels > 20% of total V beta gene expression in nine of 15 individuals. Analysis of paired biopsy and blood specimens revealed a preferential expression of specific V beta genes, such as V beta 3, V beta 5, and V beta 8, at sites of Kveim-Siltzbach reactions to levels four to seven times that of the corresponding peripheral blood. Sequence analysis demonstrated that preferential expression of specific V beta genes at Kveim-Siltzbach reaction sites is oligoclonal. Furthermore, the dominant V beta 8 sequence present at one of the reaction sites contained a sequence motif in the variable-diversity-joining junctional region previously identified in sarcoid lung and blood T cell populations. These results suggest that the Kveim-Siltzbach reaction is characterized by a limited TCR beta-chain repertoire consistent with an Ag-driven T cell immune response.

Selective activation and accumulation of oligoclonal V beta-specific T cells in active pulmonary sarcoidosis.

Sarcoidosis is a granulomatous disease in which activated T cells, responding to an unidentified stimulus, accumulate at sites of disease such as the lung. To evaluate the hypothesis that active sarcoidosis is characterized by a selective activation and expansion of a limited repertoire of T cell receptor (TCR) specific T cells, we analyzed TCR V beta gene expression in lung and blood T cells of patients with active sarcoidosis and, for comparison, normal individuals using polymerase chain reaction amplification of 20 V beta gene families. Analysis of normal bronchoalveolar lavage T cells revealed TCR V beta distributions similar to that of normal blood, providing evidence for a lack of generalized skewing of the T cell repertoire in the normal, noninfected lung. Compared to normal lung and blood, subgroups of individuals with sarcoidosis demonstrated biased expression of one or more V beta genes in either the lung or blood. Five V beta gene families (V beta 5, V beta 8, V beta 15, V beta 16, and V beta 18) were most frequently utilized in a biased fashion by sarcoid lung or blood T cells. Furthermore, dramatic skewing of the T cell repertoire was apparent when sarcoid lung and blood T cells were expanded by short-term culture with IL-2. Sequence analysis demonstrated a bias in V beta gene expression was usually due to expansion of select V beta-specific clones, some of which contained a similar V(D)J junctional region motif. These observations provide evidence for a selective activation and accumulation of antigen-specific V beta-expressing T cells in sarcoidosis.

3-substituted-1,2-benzisoxazoles: novel antipsychotic agents.

A series of 3-substituted-6-fluoro-1,2-benzisoxazoles (II) was synthesized and evaluated for potential antipsychotic activity. Many of the compounds displayed potent antipsychotic-like activity in the apomorphine induced climbing in mice (CMA) or spiroperidol binding assays, and compound 42 (HRP 392, 1-[3-(6-fluoro-1,2-benzisoxazol-3-yl)propyl]-4-(2-methoxyphenyl) piperazine) was selected for more detailed antipsychotic evaluation in a battery of preclinical assays. The results of these studies suggests that 42 is a potential antipsychotic drug with less propensity for EPS than some standard neuroleptics in monkeys. The compound was advanced for toxicological evaluation.

Determination of HP 749, a potential therapeutic agent for Alzheimer's disease, in plasma by high-performance liquid chromatography.

N-(n-Propyl)-N-(4-pyridinyl)-1H-indol-1-amine hydrochloride (HP 749, I), a non-receptor-dependent cholinomimetic agent with noradrenergic activity, is a potential agent for the treatment of Alzheimer's disease. Pharmacokinetic studies in animals and humans showed that I was well absorbed and metabolized primarily to the N-despropyl metabolite (P7480, II) after oral administration. To facilitate the kinetic studies, a sensitive and selective high-performance chromatographic assay was developed. I and II are extracted from plasma by a mixture of cyclohexane-ethyl acetate and chromatographed on an isocratic reversed-phase high-performance liquid chromatographic system employing an analytical phenyl column with acetonitrile-ammonium formate as mobile phase. The concentrations of these two compounds, quantitated by internal standardization, are monitored by ultraviolet detection. The method is linear in the plasma assay over a concentration range of 0.5-500 ng/ml for both compounds with a quantitation limit of 0.5 ng/ml. The precision and accuracy of the calibration curves and/or method are less than 10%. The recovery of I and II from plasma is 63-74 and 63-68%, respectively, over a concentration range of 0.5-500 ng/ml.