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Biomedical subjects

Rolf Beetz

Publications and source records attributed to Rolf Beetz.

9 recordsLinked to original sources
PubMed2006

Characteristics of hearing loss in HDR (hypoparathyroidism, sensorineural deafness, renal dysplasia) syndrome.

Haploinsufficiency of the zinc finger transcription factor GATA3 causes the triad of hypoparathyroidism, deafness and renal dysplasia, known by its acronym HDR syndrome. The purpose of the current study was to describe in detail the auditory phenotype in human HDR patients and compare these to audiometrical and histological data previously described in a mouse model of this disease. Pure tone audiometry, speech audiometry, speech in noise, auditory brainstem responses and transiently evoked otoacoustic emissions were measured in 2 patients affected by HDR syndrome. Both patients were affected by a moderate-to-severe sensorineural hearing loss. Speech reception thresholds were shifted and speech recognition in noise was disturbed. No otoacoustic emissions could be generated in either patient. Auditory brainstem response interpeak intervals were normal. The human and murine audiological phenotypes seem to correspond well. Hearing loss in HDR syndrome is moderate to severe, seems to be slightly worse at the higher end of the frequency spectrum and may be progressive with age. The absence of otoacoustic emissions and the loss of frequency selectivity suggest an important role for outer hair cells in causing the hearing loss.

Adult↗
PubMed2006

Late-onset manifestation of antenatal Bartter syndrome as a result of residual function of the mutated renal Na+-K+-2Cl- co-transporter.

Genetic defects of the Na+-K+-2Cl- (NKCC2) sodium potassium chloride co-transporter result in severe, prenatal-onset renal salt wasting accompanied by polyhydramnios, prematurity, and life-threatening hypovolemia of the neonate (antenatal Bartter syndrome or hyperprostaglandin E syndrome). Herein are described two brothers who presented with hyperuricemia, mild metabolic alkalosis, low serum potassium levels, and bilateral medullary nephrocalcinosis at the ages of 13 and 15 yr. Impaired function of sodium chloride reabsorption along the thick ascending limb of Henle's loop was deduced from a reduced increase in diuresis and urinary chloride excretion upon application of furosemide. Molecular genetic analysis revealed that the brothers were compound heterozygotes for mutations in the SLC12A1 gene coding for the NKCC2 co-transporter. Functional analysis of the mutated rat NKCC2 protein by tracer-flux assays after heterologous expression in Xenopus oocytes revealed significant residual transport activity of the NKCC2 p.F177Y mutant construct in contrast to no activity of the NKCC2-D918fs frameshift mutant construct. However, coexpression of the two mutants was not significantly different from that of NKCC2-F177Y alone or wild type. Membrane expression of NKCC2-F177Y as determined by luminometric surface quantification was not significantly different from wild-type protein, pointing to an intrinsic partial transport defect caused by the p.F177Y mutation. The partial function of NKCC2-F177Y, which is not negatively affected by NKCC2-D918fs, therefore explains a mild and late-onset phenotype and for the first time establishes a mild phenotype-associated SLC12A1 gene mutation.

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↗
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

GATA-3 in human T cell helper type 2 development.

The delineation of the in vivo role of GATA-3 in human T cell differentiation is a critical step in the understanding of molecular mechanisms directing human immune responses. We examined T cell differentiation and T cell-mediated effector functions in individuals lacking one functional GATA-3 allele. CD4 T cells from GATA-3+/- individuals expressed significantly reduced levels of GATA-3, associated with markedly decreased T helper cell (Th)2 frequencies in vivo and in vitro. Moreover, Th2 cell-mediated effector functions, as assessed by serum levels of Th2-dependent immunoglobulins (Igs; IgG4, IgE), were dramatically decreased, whereas the Th1-dependent IgG1 was elevated compared with GATA-3+/+ controls. Concordant with these data, silencing of GATA-3 in GATA-3+/+ CD4 T cells with small interfering RNA significantly reduced Th2 cell differentiation. Moreover, GATA-3 mRNA levels increased under Th2-inducing conditions and decreased under Th1-inducing conditions. Taken together, the data strongly suggest that GATA-3 is an important transcription factor in regulating human Th2 cell differentiation in vivo.

Adolescent↗
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↗