HLA-DRB1,3,4,5 and -DQB1 allele frequencies and HLA-DR/DQ linkage disequilibrium of 231 German caucasoid patients and their corresponding 821 potential unrelated stem cell transplants.

Allelic matching within the HLA-DRB1 and -DQB1 loci significantly improves the clinical outcome of hematopoietic stem cell transplantation. Consequently, allelic typing of these loci is strongly recommended for the unrelated stem cell donor selection. In this study, the HLA-DRB1,3,4,5 and -DQB1 alleles of 231 patients and their corresponding 821 nonrandom potential stem cell donors were determined to define compatible donor/recipient pairs. Highly accurate HLA typing data were achieved by PCR-SSOP and a combination of group specific PCR-SSP and subsequent sequencing-based typing of nearly the whole second exon of each locus. The alleles DRB1*07, *09, and *10 were analyzed by PCR-reverse dot blot hybridization instead of sequencing. Additionally, DRB1 homozygosity was verified by temperature gradient gel electrophoresis. The identified 2104 HLA-DRB1 and HLA-DQB1 alleles as well as data on HLA-DRB3, -DRB4, and -DRB5 alleles were applied to a statistical program and absolute and relative delta values of DR/DQ linkages were calculated. The achieved data on the HLA-DRB1 allele distribution and on DR/DQ associations in terms of subtypes significantly ensure the typing reliability, since rare allele combinations will result in further investigations. Furthermore, detailed data on the DR/DQ allele associations allow estimations of the number of HLA-A, -B, and -DR matched unrelated stem cell donors necessary for the identification of DRB and DQB subtype identical donors.

Fundamental Studies of Fiber-Guided Soft Tissue Cutting by Means of Pulsed Midinfrared Lasers and their Application in Ureterotomy.

Fiber-guided ablation of soft tissue with pulsed holmium and thulium lasers was investigated for intraluminal incisions. A bare fiber/tissue-contact application system with a nearly tangential irradiation geometry was first used in vitro on porcine ureter tissue. The efficiency and precision of the method was analyzed for different laser and application parameters. The ablation dynamics in water and tissue was investigated by fast flash photography. Uniform cuts could be achieved with 200- and 318-µm fibers using a free-running holmium laser with a pulse repetition rate of 10 Hz and an average power of up to 4 W. The depth of the cuts could be increased by using a thulium laser with the same laser parameters. By reducing the pulse duration by one order of magnitude, the quality of the incisions was made more irregular, the zone of thermomechanical damage increased, and the cuts became deeper owing to the growing influence of cavitation on shorter laser pulse durations. In a first clinical trial, 20 patients underwent holmium laser therapy to reopen ureteral strictures. Neither bleeding nor other adverse effects due to the laser treatment occurred, showing IR laser ureterotomy to be a suitable and promising minimally invasive technique. © 1998 Society of Photo-Optical Instrumentation Engineers.

Follow-up measurements of Nevirapine plasma levels over a prolonged period.

Over a period of more than four years of treatment, 177 Nevirapine plasma levels were taken from 27 patients. The values showed a high inter-patient variability and a lower intra-patient variability. Differences in body weight turned out to be the main reason for inter-patient variability. Treatment over a prolonged period did not result in any change in plasma concentrations. Adjusting dosage by means of therapeutic drug monitoring would appear to be a reasonable way of maximising patient benefit from treatment.

[BCG in reflux]. / BCG bei Reflux.

Nine patients with radiologically proven vesicorenal reflux (3 bilateral, 4 unilateral, 2 with unilateral double-J stents) received intravesical bacillus Calmette-Guérin (BCG) as prophylactic treatment for recurrent superficial bladder carcinoma. One patient with a double-J stent suffered an attack of high fever, probably following obstruction of the stent. All other patients tolerated one cycle or two cycles (5 of 9 patients) of 6 weekly instillations without significant complications. There was no increased toxicity compared with a control group of 39 patients without reflux who were receiving BCG. Topical intravesical immunotherapy with BCG in patients with vesicorenal reflux can be given without a rise in the complication rate; indeed, in view of the multifocal appearance of urothelial carcinoma in this subgroup, this type of therapy even appears to be desirable.

[Testicular metastasis of prostatic carcinoma 3 years after subcapsular orchiectomy. A case report]. / Hodenmetastase eines Prostatakarzinoms drei Jahre nach subkapsulärer Orchiektomie. Ein Fallbericht.

Metastatic cancer to the testis is a rare phenomenon of prostate carcinoma with only 80 cases reported in the literature. Most of these secondary testicular tumors were diagnosed on routine pathohistological examination of testicular tissue after plastic orchiectomy. In none of these cases metachronous development of these metastases has been described. For the first time we report on a 75-year old patient who developed a prostate carcinoma metastatis to the right testicle three years after undergoing subcapsular orchiectomy. This case shows that the urologist has to think about a metastatic cancer when he sees a testicular tumor also after plastic orchiectomy.

[Ureterorenoscopy in children]. / Ureterorenoskopie bei Kindern.

Ureterolithiasis is rare in children. Although ureterorenoscopy is needed only in few cases, because of the small number of children who suffer from ureteral stones, the development of small-calibre semi-flexible instruments for the treatment of any ureteral stones can be seen as a useful extension of the range of therapeutic options. The established technique used in adults can also be applied in children. It is recommended that endoscopic stone treatment should be carried out in children only by operators who can draw on a wide experience of such procedures in adults. The small-calibre instruments must be used and extreme caution is still required. We report on our experience with ureterorenoscopy in 12 children.

[Diverticular calculi of the kidney calices--extracorporeal shockwave lithotripsy, percutaneous extraction or open surgery]. / Kelchdivertikelsteine--ESWL, perkutane Litholapaxie oder offene Operation.

The incidence of caliceal diverticula, mostly found on routine excretory urography, is very low. The indications for treatment include chronic or recurrent pyelonephritis, pain, gross hematuria and renal damage. There is controversy as to which treatment is best: extracorporeal shock-wave lithotripsy (ESWL), percutaneous techniques, or traditional open surgery. Since 1984, 27 patients with 28 caliceal diverticula calculi have been treated. Ten patients underwent ESWL, 13 patients percutaneous treatment, and 4 patients open surgery. The success rates as far as a stone-free status is concerned were: 1 patient (ESWL), 10 (percutaneous), and 4 (open surgery). There were no complications due to ESWL or open surgical treatment. Direct traumata such as severe bleeding in two and hydrothorax in one patient occurred during the training phase of the percutaneous techniques. Due to the low complication rate, non-invasive ESWL treatment should be tried first. The indications for percutaneous removal of calculi in caliceal diverticula depend on two aspects: it should be possible to puncture the caliceal diverticula via by a short parenchymal route coaxial to the axis of the calix and, if the intercostal approach is used, a pleural lesion must be excluded. If these requirements cannot be fulfilled, open surgical treatment should be performed, especially if the diverticula are located in the upper and anterior part of the kidney.

[Laser lithotripsy with automatic shut-off on tissue contact]. / Laserlithotripsie mit automatischer Abschaltung bei Gewebekontakt.

A group of 88 patients with 89 ureteral calculi were treated with the pulsed dye-laser. Visual control was carried out through 8.5-F or 9.5-F ureteroscopes. The laser has automatic shut-off via spectrum analysis of back-scatter laser light. Effective laser pulses can therefore only be induced in the case of contact with the stone. Of the 89 stones 58 (65.2%) were completely fragmented by laser lithotripsy, 15 (16.8%) by laser lithotripsy in combination with ESWL and 9 (10.1%) by other ureteroscopic techniques. Ureterolithotomy was necessary only in 1 case (1%). There were 5 calculi (5.6%) that were too hard for fragmentation. The pulsed dye-laser is a safe and effective treatment modality for ureteral calculi that are not accessible for ESWL or in which ESWL has been unsuccessful. Further experimental and clinical trials will have to show whether miniature probes for electrohydraulic lithotripsy, dye-laser with automatic shut-off, or alexandrite laser will be the method of choice for lithotripsy of ureteral calculi.

[Suture-free amniotic membrane transplantation]. / Nahtlose Amnionmembrantransplantation.

Amniotic membrane transplantation has been used very successfully in ophthalmology since the 1940s for treatment of surface disorders. Over the course of the years the indications for use have been continuously extended. In contrast the operative technique is predominantly invasive, i.e. the amniotic membrane is surgically sutured onto the surface of the eye. In order to avoid surgical trauma the authors have developed a device which allows the amniotic membrane to be stretched in a ring and the amniotic ring can then be placed suture-free on the eye surface. The authors are hopeful that the biological principle of the amniotic membrane can be better utilized by uncomplicated repetitive application.

[Secondary malignancies in urinary diversions]. / Sekundärmalignome in Harnableitungen.

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.

Applicability of cord blood-derived unrestricted somatic stem cells in tissue engineering concepts.

OBJECTIVES: Cell-based tissue engineering concepts are becoming an important therapeutic alternative in the treatment of traumatic or chronic skeletal diseases. Here, we have evaluated cord blood-derived unrestricted somatic stem cells (USSCs) for use in bone and cartilage repair strategies. METHODS AND RESULTS: This type of somatic stem cell can be generated from cord blood with a current rate of 29% and we have documented excellent proliferation potential to high passage numbers. The cells have an initial population doubling time of 39 h, which slightly decreased with increasing passage number, but cells maintained their proliferation abilities up to passage 23. Cells clearly differentiated towards chondrogenic, adipogenic and osteogenic lineage as shown by reverse transcription-polymerase chain reaction as well as by histological, biochemical and immunohistochemical stains. Differentiation potential of USSCs was observed at passage 6, passage 15 and passage 21. In addition, USSCs showed increased secretion of vascular endothelial growth factor (VEGF) during osteogenic differentiation, as well as expression of key markers of angiogenesis such as vascular endothelial growth factor receptor-2 and platelet/endothelial cell adhesion molecule. CONCLUSIONS: USSCs when transplanted into a bone defect might support the repair process not only by pure remineralization but also by installation of angiogenic environment.

Extracorporeal shock wave lithotripsy in paediatric patients.

24 children with urolithiasis of the upper urinary tract were treated by extracorporeal shock wave lithotripsy (ESWL). In all patients sufficient stone disintegration could be achieved by an average of 950 shock waves. Percutaneous nephrostomy was required for "Steinstrasse" ureteral obstruction in 2 cases. At discharge from hospital 16 children were considered stone-free. Follow-up showed 90% of the children to be stone-free without recurrence (mean 20 months). The necessary precautions considered, ESWL is the method of choice for treatment of urolithiasis of the upper urinary tract in children. The long term effects of ESWL on the juvenile kidney have yet to be observed.

[Malignant degeneration of experimental ulcerative colitis of the rat following s.c. injection of 1,2-dimethylhydrazine (author's transl)]. / Maligne Entartung der Colitis ulcerosa im Experiment

Animal experiments were performed to answer the question whether ulcerative colitis is predisposed to malignant degeneration. Male Wistar rats were given aqueous solutions of degraded Carrageenan (4%; w/v). After induction of ulcerative colitis, 1,2-Dimethylhydrazine (DMH; 132 mg/kg body weight) was applicated during a period of 7 weeks. 17 of 18 rats developed multiple adenocarcinomas in the distal colon 15 weeks after the last injection of DMH. The Carrageenan induced colitis was localized predominantly in the distal part of the large bowel. Only 3 rats of a control group of 18 animals exposed to DMH only showed carcinomas of the colon. The difference is proven significant (P less than 0.01). Carrageenan for itself caused no malignancy. The results of the experiments demonstrate that, during ulcerative colitis, the colon of the rat is more susceptible to induction of cancer than the intact one.

Surgical emergency cases--endoscopic treatment.

For gastrointestinal surgery endoscopy gains more and more importance. Besides the desired improvement of pre-, intra- and postoperative diagnosis multiple therapeutic procedures proved to be practicable. Of special interest are those methods, which can be used successfully in emergency cases. Here the foreign body dislodgement, the stopping of hemorrhage and the introduction of tubes in cases of ileus or dehiscence of the suture have to be mentioned. The endoscopic treatment is very often a complementary or palliative one and not so much an alternative. These methods are applied to patients at high risk.

[Duodenogastric reflux and anastomosis abscess. Experimental study]. / Duodenogastrischer Reflux und Anastomosengeschwür. Eine experimentelle Studie

Different types of duodenal by-pass operations with and without duodenogastric reflux were performed on 54 male Wistar rats. The results of our investigation show that following duodenal by-pass with reflux peptic anastomotic ulcer regularly occurs. The constant reflux of bile and pancreas juice is the most important aetiologic factor in the development of ulcer in the vicinity of the anastomosis between the stomach and small intestine. Stasis in the by-passed duodenum (afferent loop syndrome) promotes ulcerogenic action of reflux. In the absence of the pylorus the effects of reflux and stasis potentiate, resulting in a high frequency of ulcer (greater than 90%). With intact pylorus the incidence is low. Duodenogastric reflux prevents hydrochloric acid secretion significantly (p less than o,o1); hydrochloric acid thus plays a minor role in the development of experimental anastomotic ulcer of the rat. -- In considering the prophylaxis against anastomotic ulcer, these findings support the claim of avoiding surgical techniques involving duodenal by-pass and reflux (Billroth II with short loop GE). Gastric resection should, therefore, aim at the reconstruction of the orthograde peristalsis.

[Medium-term results in cement-free endoprosthetics: the Lord prosthesis]. / Mittelfristige Ergebnisse zementfreier Endoprothetik: Lord-Prothese.

In a clinical and radiological follow up 64 Lord-endoprostheses could be controlled after a meantime of 8.5 years. The positive judgement of the patients, which is caused by the reduction of pain, is in contrast to the poor improvement of gait and mobility. Radiological findings are suspicious for a higher rate of loosening of the cup and fractures of the shaft.

Bacillus Calmette-Guérin treatment and vesicorenal reflux.

14 patients with radiologically documented vesicorenal reflux (5 bilateral, 7 unilateral, 2 unilateral double-J stents) received intravesical immunotherapy with bacillus Calmette-Guérin (BCG) after treatment of their superficial urothelial tumors. 1 patient with a double-J stent suffered a highly febrile attack following obstruction of the indwelling ureteral catheter. The other patients tolerated 1 or 2 (6 of 14 patients) courses of BCG without an increase in side effects. Topical intravesical therapy with BCG in patients with vesicorenal reflux seems to be indicated in view of the multicentricity of urothelial carcinoma and can be performed without an increased risk of complications.

[Ureterorenoscopy as a diagnostic procedure in the upper urinary tract]. / Die Ureterorenoskopie als diagnostisches Verfahren im oberen Harntrakt.

Ureteropyeloscopy has become a valuable asset in the diagnosis and treatment in the upper urinary tract. From 1984 to 1991 we performed 1635 ureteropyeloscopies, 180 procedures in a diagnostic intention. Rigid ureteropyeloscopes permit endoscopic access into the ureter and the upper calix, actively deflectable instruments are necessary to visualize the middle and lower calix.