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Biomedical subjects

Raimund Stein

Publications and source records attributed to Raimund Stein.

At least 19 recordsLinked to original sources
PubMed2026

Genital surgery in children with differences of sex development (DSD): Strengths and concerns across diverging regulations in four European countries.

Differences of Sex Development (DSD) is a collective term for a heterogeneous group of rare congenital conditions characterized by atypical genetic, gonadal, or genital sexual development. The treatment of children with DSD, particularly the indications for and timing of surgical interventions, has been the subject of debate for decades. In recent years, social developments emphasizing children's rights to self-determination and bodily integrity, along with increasing societal acceptance of atypical sex characteristics, have encouraged a more cautious approach toward early genital surgery in children with DSD. In 2019, the European Parliament adopted a resolution urging Member States to enact legislation prohibiting elective genital surgical interventions on intersex infants and children. Since then, several countries have indeed implemented restrictive measures, including legal bans on early surgical procedures. In this paper, we share the experiences and insights gained in recent years as pediatric urologists working in four neighboring countries in multidisciplinary university centers specializing in DSD care and research. We focus on current approaches to the care of children with DSD, the evolution of relevant national policies over time, and the nature and impact of recently introduced restrictive regulations on early surgical interventions. By presenting perspectives from pediatric urologists across these four countries, we aim to contribute to ongoing discussions on the alignment and refinement of surgical treatment practices for children with DSD.

Humans↗
PubMed2007

Expression of somatic DNA repair genes in human testes.

Meiosis is the key process for recombination and reduction of the diploid chromosome set to a haploid one. Many genes that have been found in yeast or mouse models to play a role in meiosis are also important for the repair of DNA damage in somatic cells. To study the DNA repair gene transcriptome during male germ cell development, we have developed a specialized cDNA microarray with 181 human genes which are involved in different somatic DNA repair pathways and/or cell cycle control and 45 control house-keeping genes. This DNA repair gene chip was used to quantify the mRNA expression levels in three human testes samples versus a fibroblast RNA pool. Two hundred twenty genes on the chip (including house-keeping genes) showed detectable expression levels in adult testes. Sixty-four DNA repair- and cell cycle-associated genes showed higher expression levels in testicular cells than in mitotically dividing fibroblasts and, therefore, are likely to be implicated in meiosis. The microarray results of 17 genes with increased expression levels were validated with reverse Northern blots or real-time quantitative RT PCR. Systematic analyses of the meiotic DNA repair gene transcriptome may provide new insights into the genetics of male (in)fertility.

Biomarkers↗
PubMed2006

Expression of DNMT3A transcripts and nucleolar localization of DNMT3A protein in human testicular and fibroblast cells suggest a role for de novo DNA methylation in nucleolar inactivation.

Transcriptional silencing during differentiation of human male germ cells and serum starvation of human fibroblasts is controlled by epigenetic mechanisms that involve de novo DNA methylation. It is associated with high expression of different transcripts of the DNA methyltransferase 3A (DNMT3A) gene that encode two isoforms with de novo methyltransferase activity and one without catalytic activity. Western blots revealed that DNMT3A protein (with catalytic domain) is present at low levels in several tissues and at increased levels in testicular cells and growth-arrested fibroblasts. Immunofluorescence experiments localized DNMT3A to discrete nucleolar foci in B spermatogonia and resting fibroblasts. The data here suggest a role for de novo DNA methylation in nucleolar inactivation.

Active Transport, Cell Nucleus↗
PubMed2006

Continent cutaneous urinary diversion: long-term follow-up of more than 800 patients with ileocecal reservoirs.

We report the clinical outcome of more than 800 patients, who underwent continent cutaneous urinary diversion with an ileocecal reservoir (Mainz-pouch I) in two urological tertiary referral centers at a mean follow-up of 7.6 years. Complications related to the continence mechanism (intussuscepted ileal nipple vs. submucosally embedded in situ appendix) and the antirefluxive uretero-intestinal anastomosis (submucosal tunnel vs. serosa-lined extramural tunnel) were recorded retrospectively. Stomal stenosis was observed in 23.5% of the patients with appendix stoma and in 15.3% of the patients with intussuscepted ileal nipple. The incidence of calculi was 10.8% in reservoirs with intussuscepted ileal nipple and 5.6% in reservoirs with appendix stoma. Eleven patients (eight with appendix, three with ileal nipple) required reoperation because of ischemic degeneration of the continence mechanism. The overall continence rate (day and night) was 92.8%. Anastomotic strictures of the afferent limb occurred in 6.5% of renal units (RUs) with a submucosal tunnel and in 5.0% of RUs with a serosa-lined extramural tunnel. Continent cutaneous urinary diversion with an ileocecal pouch is a highly satisfactory and safe option for patients, in whom orthotopic urinary diversion is impossible or contraindicated.

Adolescent↗
PubMed2006

Rectosigmoid pouch (Mainz Pouch II) in children.

PURPOSE: Continent anal urinary diversion is a therapeutic option in bladder exstrophy. We report our long-term results with the rectosigmoid pouch (Mainz pouch II), a modification of the classic ureterosigmoidostomy. MATERIALS AND METHODS: A total of 38 children with a mean age of 5 years (range 0.5 to 17) underwent a Mainz pouch II procedure between 1991 and 2004. Most patients (33) had bladder exstrophy or incontinent epispadias. In 14 children (37%) urinary diversion was performed after failed primary reconstruction. In 6 children conversion was performed from an incontinent type of urinary diversion. Renal function, continence and metabolic changes were analyzed. A total of 35 children were followed for a mean of 112 months (range 5 to 147). RESULTS: All children were continent during the daytime but 3 (8.6%) suffered from nighttime incontinence requiring pads. With respect to the upper urinary tract, 6 children (15.8%) had development of pyelonephritis, mostly with stenosis of the ureterointestinal anastomosis. Reimplantation of the ureter was required in 10 of 69 RU (14.5%), of which 7 (10.1%) were due to ureterointestinal stenosis and 3 (4.3%) were due to reflux. Serum creatinine was within normal limits in all children. During followup acid-base balance was monitored, and early alkali supplementation was initiated in 24 of 35 children (69%) when the base excess was less than -2.5 mmol/l. One child had development of clinical acidosis requiring hospitalization. After followup of more than 10 years annual rectosigmoidoscopy was performed in 16 children/young adults without pathological findings. CONCLUSIONS: The Mainz pouch II procedure for children with genitourinary anomalies promises excellent continence rates. However, periodic followup studies are important to check the upper urinary tract and prevent metabolic acidosis. Due to the risk of malignancy at the ureterointestinal anastomosis, endoscopy should be performed annually beginning at postoperative year 10. The Mainz pouch II procedure is safe in the long term. Without stoma, appliance or catheterization this type of continent urinary diversion is specifically suitable for children.

Adolescent↗
PubMed2006

Long-term followup of the intussuscepted ileal nipple and the in situ, submucosally embedded appendix as continence mechanisms of continent urinary diversion with the cutaneous ileocecal pouch (Mainz pouch I).

PURPOSE: We analyzed stoma related complications and continence rates in patients who underwent continent urinary diversion with the cutaneous ileocecal pouch (Mainz pouch I). We compared the intussuscepted ileal nipple and in situ, submucosally embedded appendix as continence mechanisms. MATERIALS AND METHODS: A total of 401 patients were included in a retrospective followup study. Continence mechanisms were the intussuscepted ileal nipple in 205 patients and the in situ, submucosally embedded appendix in 196. RESULTS: A total of 144 patients (36%) required intervention for a stomal complication. Of patients who received an intussuscepted ileal nipple 34 (17%) had stomal stenosis at a mean time to first stenosis of 43.8 months, 41 (20%) had stones at a mean interval to the first stone of 62.8 months, 12 underwent reoperation for stomal incontinence, including 1 because of nipple necrosis, and 82% were completely continent. Of patients who received an in situ, submucosally embedded appendix 63 (32%) had stomal stenosis at a mean time to first stenosis of 31.4 months, 20 (10%) had stones at a mean interval to the first stone of 47.5 months, 3 underwent reoperation for stomal incontinence, 4 had appendiceal necrosis and 92% were completely continent. CONCLUSIONS: Of stomal complications 63% were treated endoscopically. The higher rate of stomal stenosis with the appendiceal stoma is most likely due to the smaller diameter of the appendix. The higher rate of stone formation in patients with the intussuscepted ileal nipple is related to metal staples. Continence rates of the 2 outlets are good with somewhat larger amounts of mucous secretion from the larger stoma of the intussuscepted ileal nipple.

Adolescent↗
PubMed2006

Conversion from colonic conduit into recto-sigmoid pouch (Mainz pouch II).

OBJECTIVE: To report our long-term results of conversion from conduit conversion into a continent anal urinary diversion, as after conduit urinary diversion in childhood, some patients wish to have a later conversion to a continent diversion to avoid external appliances and to improve their quality of life. PATIENTS AND METHODS: Between 1992 and 2003, 139 patients had a urinary diversion with a recto-sigmoid pouch (Mainz pouch II), of whom four had a conversion from a colonic conduit diversion to a recto-sigmoid pouch. The mean (range) age at conduit diversion was 5.5 (3-14) years and the mean interval between conduit diversion and conversion to a continent anal diversion was 8 (4-18) years. The mean age at conversion into a Mainz pouch II was 13 (8-32) years and the follow-up afterward was 11.5 (1-13) years. The conversion was done by incorporating the pre-existing colonic conduit into the recto-sigmoid pouch with no ureteric reimplantation. RESULTS: There were no early complications; one nephrectomy was required 5 years after conversion because of uretero-intestinal obstruction and pyelonephritis. All other reno-ureteric units remained stable and renal function was maintained. All patients are continent day and night; three require substitution with alkali at a base excess of < -2.5 mmol/L to prevent hyperchloraemia and acidosis. CONCLUSION: The recto-sigmoid pouch is a therapeutic option when patients desire conversion from an incontinent type of urinary diversion to a continent type.

Adolescent↗
PubMed2005

Urinary diversion in children and adolescents with neurogenic bladder: the Mainz experience. Part II: Continent cutaneous diversion using the Mainz pouch I.

After failure of conservative treatment of neurogenic bladders (deterioration of the upper urinary tract/incontinence) continent cutaneous diversion has to be considered in those patients with irreparable urethral sphincter defects or those who are unable to perform trans-urethral self-catheterization. In this second part of the study we investigated the long-term safety of using the Mainz pouch I with regard to protecting the upper urinary tracts and to provide urine continence. Between 1985 and 2002, operations to form an ileocaecal pouch with umbilical stoma (Mainz pouch I) were performed on 70 children and adolescents of median age 15.3 years (range 5.7-20 years). During the follow-up period five patients died 2.4-14 years postoperatively of causes not related to urinary diversion. A follow-up period of 8.7 years (0.9-18) was achieved in 65 patients with 118 renal units (RUs). As compared to preoperatively, the upper urinary tracts had remained stable or improved in 113/118 RUs (95.8%) at the latest follow-up. Complete continence was achieved in 97% of patients with a continent cutaneous diversion. Surgical revisions were required for: incontinence of the outlet mechanism in 9%, stoma prolapse in 2%, stoma stenosis in 23%, pouch calculi in 15%, symptomatic reflux in 1%, ureter stenosis in 16% of the RUs with submucosal tunnel and in 3% of the RUs with an extramural tunnel. We conclude that, in patients with irreparable sphincter defect and those who are unable to perform urethral self-catheterization, continent cutaneous urinary diversion with the Mainz pouch I provides a high continence rate with preservation of the upper urinary tracts in the long run. In patients with dilated ureters, the extramural tunnel technique results in a lower complication rate.

Acid-Base Equilibrium↗
PubMed2005

Urinary diversion in children and adolescents with neurogenic bladder: the Mainz experience. Part III: Colonic conduit.

After the failure of conservative treatment of neurogenic bladders, urinary diversion has to be considered. For patients with chronic renal failure, severe dilated upper urinary tracts with deterioration of the renal function and those who are not able to perform a self-catheterization, the colonic conduit diversion is our therapy of choice. In this part of the study, we investigate the long-term safety of our concept for these patients in regard to protecting the upper urinary tracts. Between 1968 and 2002, colonic conduit urinary diversion was performed in 88 patients, in most of them in the era before continent diversion. Overall, 11 patients with a colonic conduit were converted to bladder substitution or continent cutaneous diversion during the follow-up period. These patients are no longer included in the long-term follow-up of colonic conduit patients. Of the 77 patients with colonic conduit diversion, 21 patients were not available for follow-up: 11 were deceased and 10 were lost to follow-up. Three of the deaths were related to nephrological complications in patients who already had impaired renal function before conduit diversion. An average follow-up of 21.8 years (2-32.7; median 23.8 years.) is available in 56 patients with 99 RUs (6 solitary kidneys, 7 nephrectomies). Five non-functioning kidneys were removed after recurrent pyelonephritis and two kidneys with pyonephrosis. Ureter stenoses were corrected in 6% of the RUs. As compared to preoperatively, the upper urinary tracts remained stable or improved in 97/99 RUs at the latest follow-up. A revision of the stoma was necessary in 16% (conduit elongation n =2, stenosis n =7) and calculi formations were treated in 8% of the RUs. For patients with chronic renal failure or who are unable to perform a catheterization of a continent stoma, the colonic conduit is a safe alternative in the long run.

Acid-Base Equilibrium↗
PubMed2005

Urinary diversion in children and adolescents with neurogenic bladder: the Mainz experience. Part I: Bladder augmentation and bladder substitution--therapeutic algorisms.

After the failure of conservative treatment of neurogenic bladders (deterioration of the upper urinary tract/incontinence), bladder augmentation/bladder substitution and supravesical urinary diversion have to be considered. In our concept, bladder augmentation is indicated for hyperreflexive and small low compliance bladders with normal upper urinary tracts. In cases with combined sphincteric incompetence, a fascial sling (FS) can be required to achieve continence. In patients with small and hyperreflexive bladders, high-grade reflux and/or dilatation of the upper tracts, bladder substitution and ureteral reimplantation are appropriate. For patients with irreparable sphincter defects and those who are unable to perform transurethral self-catheterization, continent cutaneous diversion is offered. For patients with chronic renal failure, deterioration of the upper urinary tract and those who are not able to perform a self-catheterization of a continent stoma, colonic conduit diversion is our therapy of choice. The current study aims to investigate the long-term safety of our concept for these patients in regard to protecting the upper tracts and providing continence. Between 1968 and 2002, 170 children and adolescents underwent surgery. Of these, 24 received an orthotopic reservoir (bladder augmentation, n =10; combined with FS, n =1; orthotopic bladder substitution with ureteral reimplantation, n =14). The material, methods and results of the remaining 146 patients are reported in parts II and III. One of the 24 patients with an orthotopic reservoir was lost to follow-up. An average follow-up of 9 years (1.3-18 years; median 8.7 years) was available in 23 patients with 42 RUs. As compared to preoperatively, the upper urinary tracts remained stable or improved in all ten patients with bladder augmentation and in 20/23 renal units (RUs) with bladder substitution at the latest follow-up. Eight of ten patients with bladder augmentation are continent. All 13 patients with bladder substitution are continent during the day; one requires a safety pad at night. Bladder augmentation has been effective in patients with hyperreflexive and small low compliance bladders and normal upper urinary tracts. In those with high-grade reflux and/or dilatation of the upper tracts, bladder substitution and ureteral reimplantation are recommended. In very selected patients a fascial sling (FS) can be required to achieve continence.

Acid-Base Equilibrium↗
PubMed2004

Murine in vitro whole bladder model: a method for assessing phenotypic responses to pharmacologic stimuli and hypoxia.

AIMS: Recent advances in genetic manipulation have allowed for over expression or deletion of selective genes in mice. This offers urologic investigators new means of understanding bladder function in the context of normal development or the response to outlet obstruction. It is important to correlate any genetic manipulations in mice with specific phenotypic properties such as voiding patterns, or muscle strip physiology. We describe a simple in vivo whole bladder preparation that may be used to study the phenotypic changes in bladder function. METHODS: Murine bladders were mounted on a 30 gauge needle and mounted in an organ chamber containing a physiologic buffer solution. Passive bladder properties were assessed with cystometry, and active contractile responses were measured in response to electrical field stimulation and agonists. The effects of hypoxia were also studied. RESULTS: Compliance in the murine bladder is dependent upon actin myosin interactions, and increased in the presence of calcium free buffer and EGTA. The sarcoplasmic reticulum plays a smaller role in the contraction of murine bladder than in other species. Murine bladder smooth muscle demonstrated a remarkable ability to withstand hypoxia. CONCLUSIONS: This simple model can be adapted to help study the murine bladder smooth muscle phenotype under highly controlled circumstances.

Adenosine Triphosphate↗
PubMed2004

Smooth muscle hypertrophy following partial bladder outlet obstruction is associated with overexpression of non-muscle caldesmon.

Partial bladder outlet obstruction (PBOO) induces remodeling of urinary bladder smooth muscle (detrusor). We demonstrate an increase in bladder wall mass, muscle bundle size, and a threefold increase in the cross-sectional area of detrusor myocytes following PBOO in male New Zealand White rabbits compared to that of controls. Some bladders with detrusor hypertrophy function close to normal (compensated), whereas others were dysfunctional (decompensated), showing high intravesical pressure, large residual urine volume, and voiding difficulty. We analyzed the expression of smooth muscle-specific caldesmon (h-CaD) and non-muscle (l-CaD) by Western blotting, RT-PCR, and real-time PCR. The expression of l-CaD is increased significantly at the mRNA and protein levels in the decompensated bladders compared to that of normal and compensated bladders. The CaD was also co-localized with myosin containing cytoplasmic fibrils in cells dissociated from obstructed bladders and cultured overnight. Our data show that the inability of decompensated bladders to empty, despite detrusor hypertrophy, is associated with an overexpression of l-CaD. The level of l-CaD overexpression might be a useful marker to estimate the degree of detrusor remodeling and contractile dysfunction in PBOO.

Animals↗
PubMed2004

Conversion from colonic or ileal conduit to continent cutaneous urinary diversion.

PURPOSE: After ileal or colonic conduit diversion some patients, particularly adolescents, desire conversion to a continent diversion to improve quality of life. We report our long-term results on conversion from conduit diversion to continent cutaneous diversion. MATERIALS AND METHODS: Between 1986 and 2001, 39 patients (mean age 24 years, range 6 to 49) underwent conversion from a colonic (21) or ileal conduit (18) to an ileocecal pouch (Mainz pouch I) with a mean followup of 102 months (range 18 to 192). Conversion was performed after a mean of 11 years (range 1 to 36) of conduit urinary diversion by incorporating the preexisting colonic/ ileal conduit and the ileocecal pouch. RESULTS: A total of 21 patients (54%) experienced complications requiring surgical intervention including stoma stenosis (13%), pouch calculi (31%) and ureteral stenosis (6 of 75 renoureteral units, 8%). Continence was achieved in 95% of patients. Defecation was unchanged in 72% of patients without treatment. In 21% fecal frequency was medically controlled (cholestyramine, loperamide) and 8% of patients had fecal frequency. During followup early substitution of alkali was performed and in 19 patients (49%) the venous base excess was less than -2.5 mmol/l to prevent hyperchloremia and acidosis. CONCLUSIONS: The inclusion of a preexisting colonic or ileal conduit decreases resection length of bowel for continent cutaneous diversion. Acceptable complication rates, stable renal function and satisfaction of patient expectations support conversion from a conduit into a Mainz pouch I as a safe and viable option in the long run.

Adolescent↗
PubMed2004

Correction of vesicoureteral reflux: where do we stand?

PURPOSE OF REVIEW: Newer techniques of molecular biology allow us to gain a better understanding of the molecular mechanism of primary urinary reflux. In recent years, diagnostic tools and treatment options for vesicoureteric reflux have dramatically changed. In this review, we want to focus on genetics, molecular biology, histology, clinical findings, diagnostic tools and newer surgical techniques for the treatment of vesicoureteric reflux published between 2003 and March 2004. RECENT FINDINGS: Recent findings have demonstrated that the renin-angiotensin-aldosterone system does not seem to be responsible for the development of primary vesicoureteric reflux. Echo-enhanced ultrasound with contrast medium in the bladder, performed by an experienced investigator, could replace the voiding cystourethrogram in follow-up studies of patients treated conservatively for vesicoureteric reflux. The sensitivity and specificity of ultrasound is in the range of 70-100% in some studies compared with the standard voiding cystourethrogram. Endoscopic treatment of vesicoureteric reflux using Defux or Macroplastique has gained more and more popularity, with success rates ranging between 60 and 86%. The surgery is performed on an outpatient basis with minimal morbidity. Long-term results after open operative techniques have demonstrated cure of reflux in over 95% of cases. SUMMARY: In the coming years, echo-enhanced ultrasound may replace the standard voiding cystourethrogram during follow-up and it may be used as an initial test in females with normal voiding patterns. Endoscopic reflux correction must be judged on the re-treatment rates and long-term success.

Animals↗
PubMed2003

Acute perirenal extravasation of urine in an infant with non-refluxing megaureter.

Perirenal extravasation of urine is a rare event in congenital uropathies, mostly observed perinatally in the case of infravesical obstruction. We describe a male infant with a primary non-refluxing obstructive left megaureter who developed an acute perirenal extravasation and ascites at the age of 4 weeks. After temporary upper urinary diversion, ureterocystoneostomy was successfully performed. Intraoperatively, the distal ureter showed an extremely narrow lumen over a distance of 3 cm. In the current literature, postnatal management of primary megaureters is preferably conservative. Our patient demonstrates an extremely rare complication demanding early surgical intervention.

Acute Disease↗
PubMed2003

Alteration in expression of myosin isoforms in detrusor smooth muscle following bladder outlet obstruction.

Partial urinary bladder outlet obstruction (PBOO) in men, secondary to benign prostatic hyperplasia, induces detrusor smooth muscle (DSM) hypertrophy. However, despite DSM hypertrophy, some bladders become severely dysfunctional (decompensated). Using a rabbit model of PBOO, we found that although DSM from sham-operated bladders expressed nearly 100% of both the smooth muscle myosin heavy chain isoform SM-B and essential light chain isoform LC17a, DSM from severely dysfunctional bladders expressed as much as 75% SM-A and 40% LC17b (both associated with decreased maximum velocity of shortening). DSM from dysfunctional bladder also exhibited tonic-type contractions, characterized by slow force generation and high force maintenance. Immunofluorescence microscopy showed that decreased SM-B expression in dysfunctional bladders was not due to generation of a new cell population lacking SM-B. Metabolic cage monitoring revealed decreased void volume and increased voiding frequency correlated with overexpression of SM-A and LC17b. Myosin isoform expression and bladder function returned toward normal upon removal of the obstruction, indicating that the levels of expression of these isoforms are markers of the PBOO-induced dysfunctional bladders.

Animals↗