Urodynamic evaluation of hypospadias repair

Purpose: We performed a cross-sectional evaluation of voiding in a population undergoing hypospadias repair to determine whether patients had urinary obstruction at various intervals of followup after the last operation. Materials and Methods: Of approximately 600 patients undergoing hypospadias repair at our department during a 30-year interval 175, 40 months to 66 years old were evaluated. Therefore, we created a cross-sectional study group for evaluation of voiding function. All patients had undergone the final operation for hypospadias at least 1 year previously and were toilet trained. Severity of the initial hypospadias was scored together with the operative technique. Parameters evaluated were medical history, physical examination and uroflowmetry using a rotating disk. Uroflowmetry data (maximum flow rate and voided volume) were plotted in age-related nomograms in 4 different age groups: less than 8 (28 patients), 9 to 14 (18), 15 to 21 (39) and more than 21 (91) years old. All flow charts were evaluated by 2 of us (J. F. A. v. d. W. and E. B.). Results: The severity of initial disease was grade 1 in 30% of the patients, grade 2 in 57%, grade 3 in 10%, grade 4 in 2% and unknown in 2%. The operative technique performed was a van der Meulen repair in 113 patients (65%), a combined Byars-Denis Browne repair in 56 (32%) and miscellaneous in 6 (3%). According to the uroflowmetry nomograms there was a tendency for an increased number of patients to have a normal maximum flow rate with increasing age. A total of 14 patients had a flow curve that suggested distal urethra obstruction and none was symptomatic. There was no difference in uroflowmetry characteristics regarding the operative technique. Conclusions: No difference in uroflowmetry could be established among the operations. There seemed to be a tendency towards improvement in uroflowmetry with increasing followup. There was no direct relationship between low maximum flow rates and clinical apparent obstruction

Glycosaminoglycans and other sulphated polysaccharides in calculogenesis of urinary stones

Naturally occurring glycosaminoglycans (GAGs) and other, semisynthetic, sulphated polysaccharides are thought to play an important role in urolithiasis. Processes involved in urinary stone formation are crystallization and crystal retention. Oxalate transport and renal tubular cell injury are determining factors in these processes. In this article experimental results concerning the possible mechanisms of action of GAGs and other sulphated polysaccharides are reviewed. GAGs are inhibitors of crystal growth and agglomeration and possibly also of nucleation. They can prevent crystal adherence, correct an abnormal oxalate flux and prevent renal tubular cell damage

FGFR3 and P53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma

Fibroblast growth factor receptor 3 (FGFR3) and P53 mutations are frequently observed in bladder cancer. We here describe the distribution of FGFR3 mutations and P53 overexpression in 260 primary urothelial cell carcinomas. FGFR3 mutations were observed in 59% and P53 overexpression in 25%. Interestingly, FGFR3 and P53 alterations were mutually exclusive, because they coincided in only 5.7% of tumors. Consequently, we propose that they characterize two alternative genetic pathways in urothelial cell carcinoma pathogenesis. The genetic alterations were reflected in the pathology and the clinical outcome, i.e., FGFR3 mutations were found in low-stage/-grade tumors and were associated with a favorable disease course, whereas P53 alterations were tied to adverse disease parameters

Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans

TRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2. TRH was undetectable in serum (< 25 pg/mL), but TRH-LI was detected with antiserum 4319 in serum of 27 normal subjects, 21 control patients, and 12 patients with carcinoid tumors (range 17-45, 5-79, and 18-16,600 pg/mL, respectively). Because serum was kept for at least 2 h at room temperature, which causes degradation of TRH, pGlu-Phe-ProNH2, and pGlu-Tyr-ProNH2, serum TRH-LI is not caused by these peptides. On high-performance liquid chromatography, serum TRH-LI coeluted with pGlu-Glu-ProNH2 (< EEP-NH2), a peptide produced in, among others, the prostate. Urine of normals and control patients also contained TRH-LI (range 1.14-4.97 and 0.24-5.51 ng/mL, respectively), with similar levels in males and females. TRH represented only 2% of urinary TRH-LI, and anion-exchange chromatography and high-performance liquid chromatography revealed that most TRH-LI in urine was < EEP-NH2. In patients with carcinoid tumors, increased urinary TRH-LI levels were noted (range 1.35-962.4 ng/mL). Urinary TRH-LI correlated positively with urinary creatinine, and the urinary clearance rate of TRH-LI was similar to the glomerular filtration rate. In addition, serum TRH-LI was increased in 17 hemodialysis patients (43-373 pg/mL). This suggests that serum < EEP-NH2 is cleared by glomerular filtration wit

Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans

TRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds most peptides with the structure pGlu-X-ProNH2. TRH was undetectable in serum (< 25 pg/mL), but TRH-LI was detected with antiserum 4319 in serum of 27 normal subjects, 21 control patients, and 12 patients with carcinoid tumors (range 17-45, 5-79, and 18-16,600 pg/mL, respectively). Because serum was kept for at least 2 h at room temperature, which causes degradation of TRH, pGlu-Phe-ProNH2, and pGlu-Tyr-ProNH2, serum TRH-LI is not caused by these peptides. On high-performance liquid chromatography, serum TRH-LI coeluted with pGlu-Glu-ProNH2 (< EEP-NH2), a peptide produced in, among others, the prostate. Urine of normals and control patients also contained TRH-LI (range 1.14-4.97 and 0.24-5.51 ng/mL, respectively), with similar levels in males and females. TRH represented only 2% of urinary TRH-LI, and anion-exchange chromatography and high-performance liquid chromatography revealed that most TRH-LI in urine was < EEP-NH2. In patients with carcinoid tumors, increased urinary TRH-LI levels were noted (range 1.35-962.4 ng/mL). Urinary TRH-LI correlated positively with urinary creatinine, and the urinary clearance rate of TRH-LI was similar to the glomerular filtration rate. In addition, serum TRH-LI was increased in 17 hemodialysis patients (43-373 pg/mL). This suggests that serum < EEP-NH2 is cleared by glomerular filtration with little tubular resorption. The possible role of the prostate as a source of urinary TRH-LI was evaluated in 11 men with prostate cancer, showing a 25% decrease in urinary TRH-LI excretion after prostatectomy (0.19 +/- 0.02 vs. 0.15 +/- 0.01 ng/mumol creatinine, mean +/- SEM). However, TRH-LI was similar in spontaneously voided urine and in urine obtained through a nephrostomy cannula from 16 patients with unilateral urinary tract obstruction (0.15 +/- 0.01 vs. 0.14 +/- 0.01 ng/mumol creatinine). These data indicate that: 1) TRH-LI in human serum represents largely < EEP-NH2, which is cleared by renal excretion; 2) part of urinary < EEP-NH2 is derived from prostatic secretion into the blood and not directly into urine; and 3) urinary < EEP-NH2 can be used as marker for carcinoid tumors

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Noninvasive Diagnosis of Bladder Outlet Obstruction in Patients with Lower Urinary Tract Symptoms Using Ultrasound Decorrelation Analysis

Item does not contain fulltextPURPOSE: We developed a noninvasive method to diagnose bladder outlet obstruction. An ultrasound based decorrelation method was applied in male patients with lower urinary tract symptoms. MATERIALS AND METHODS: In 60 patients ultrasound data were acquired transperineally while they were voiding while sitting. Each patient also underwent a standard invasive pressure flow study. RESULTS: High frequent sequential ultrasound images were successfully recorded during voiding in 45 patients. The decorrelation (decrease in correlation) between subsequent ultrasound images was higher in patients with bladder outlet obstruction than in unobstructed patients and healthy volunteers. ROC analysis resulted in an AUC of 0.96, 95% specificity and 88% sensitivity. A linear relationship was fitted to the decorrelation values as a function of the degree of obstruction represented by the bladder outlet obstruction index, measured in the separate pressure flow studies. CONCLUSIONS: It is possible to noninvasively diagnose bladder outlet obstruction using the ultrasound decorrelation technique