Biomedical subjects
Mehmet Baykara
Publications and source records attributed to Mehmet Baykara.
Differential expression of TRAIL and its receptors in benign and malignant prostate tissues.
PURPOSE: Because TRAIL (tumor necrosis factor related apoptosis inducing ligand) selectively kills cancer cells without damaging normal cells, a gene therapy approach using TRAIL is feasible for treating patients with cancer. However, recent publications suggest that significant portions of human tumors appear to be TRAIL resistant. Furthermore, there is some controversy about whether TRAIL receptor composition influences TRAIL sensitivity in cancer cells. Our recent studies suggest that TRAIL receptor composition is the major modulator of TRAIL sensitivity, as demonstrated using prostate, breast and lung cancer cells. We investigated TRAIL and TRAIL receptor expression profiles during prostate carcinogenesis to evaluate their potential as biomarkers and predict the feasibility of a related gene therapy approach. MATERIALS AND METHODS: Paraffin embedded prostate tissues of 44 patients with benign prostatic hyperplasia, 28 with organ confined prostate carcinoma and 26 with advanced prostate carcinoma were analyzed using immunohistochemical staining procedures. RESULTS: Significant levels of TRAIL-R4 decoy receptor expression were detected in patients with benign prostatic hyperplasia, and organ confined and advanced prostate carcinoma. All TRAIL markers tested appear to be valuable markers for separating patients with benign prostatic hyperplasia from patients with organ confined prostate carcinoma or advanced prostate carcinoma. CONCLUSIONS: Due to high TRAIL-R4 expression in all patient groups complementary gene therapy modalities might be needed to bypass potential TRAIL-R4 induced resistance.
The Fas system may have a role in male reproduction.
OBJECTIVE: To assess what the distributions of Fas system proteins are in normal rat testicular tissue; to assess whether there is a change in these distributions and in expression levels with experimentally-induced varicocele of 9, 11, and 13 weeks; and to assess whether there is a relationship between apoptosis and the Fas system in varicocele-induced rat testis. DESIGN: Comparative and controlled study. SETTING: University animal care and operation unit. ANIMAL(S): Wistar male rats for experimental and control groups. INTERVENTION(S): The control group underwent sham operation (n = 6). Rats in experimental groups underwent partial ligation of the renal vein to induce an experimental varicocele and then were killed at 9 (n = 6), 11 (n = 6), and 13 (n = 6) weeks after induction of varicocele. MAIN OUTCOME MEASURE(S): Tissues were fixed and processed for paraffin and Araldite embedding, and subsequently immunohistochemistry, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling, and transmission electron microscopy were performed. In addition, Western blotting was applied. RESULT(S): In control testis, we detected the expression of FasL in spermatids, interestingly at the progressing stages of acrosome formation and in the heads of the spermatozoa being released to lumen. Varicocele induction revealed a significant down-regulation of this protein, especially 11 weeks after the operation, without altering its distribution. Fas protein was present in cytoplasmic extrusions of the elongated spermatids and evidently in Leydig cells of the interstitial tissue. The expression of Fas protein was diminished after 11 weeks of varicocele induction, both in Leydig cells and in cytoplasmic extrusions. The decrease of Fas was significant in the 13-week-old varicocele group, whereas that of FasL was significant in the 11-week-old varicocele group. Compared with sham-operated animals, a minor increase in the number of apoptotic germ cells in varicocele groups was detected. CONCLUSION(S): Our results exposed other possible important roles of the Fas system in addition to than apoptosis in male reproduction. We suggest that the role of the Fas system needs further investigation both in animal models and in human male infertility.
Localization of NGF and nNOS in varicocele-induced rat testis.
Nerve growth factor (NGF) is synthesized in male germ cells. The presence of neuronal nitric oxide synthase (nNOS) in Leydig cells is related to its role in the regulation of testosterone release. Varicocele is often characterized by abnormal sperm quality and influences the fertilizing capacity of the haploid gamete. We investigated the localization of NGF and nNOS in testes of adult Wistar rats with experimentally induced varicocele after 9, 11, and 13 weeks, as well as in sham-operated controls by immunohistochemistry and Western blot. In control testis, we detected NGF in nuclei of Sertoli cells and also as small vesicular-like structures in the cytoplasm of primary spermatocytes, and in round and elongating spermatids. Varicocele-induction revealed a slight decrease of NGF at 13 weeks, especially in Sertoli cells. In control tissue, nNOS protein was present mainly in Leydig cells and in Sertoli cell cytoplasm. Additionally, nNOS immunoreactivity was present in the heads of elongated spermatids. Western blot results revealed that the decrease of NGF was not significant in the 13-week varicocele group, moreover, the amount of nNOS was not altered in any of the varicocele groups. In conclusion, NGF and nNOS have important roles for normal gametogenesis and our data for the first time indicates that varicocele induction does not necessarily affect the expression of NGF and nNOS. Thus, these two molecules do not appear to be related to varicocele induction.
Ultrastructural and immunohistochemical analysis of rat uroepithelial cell junctions after partial bladder outlet obstruction and selective COX-2 inhibitor treatment.
The present study was undertaken to evaluate alterations in uroepithelial cell junctional complexes in partial bladder outlet obstruction (PBOO) of rat bladders using ultrastructural morphometry and immunohistochemistry, and to determine whether selective COX-2 inhibitors have any effects on these structures. A total of 18 male rats were separated into three groups of six rats each: (1) sham-operated animals served as controls; (2) a PBOO group, without further treatment (3) and a group that immediately after PBOO, received treatment for 4 weeks with oral Celecoxib, a selective COX-2 inhibitor. Uroepithelial cell junctions were evaluated using transmission electron microscopy combined with morphometry. Results were also assessed by E-cadherin and alpha-catenin immunohistochemistry. Morphometrical analysis of ultrastructural evaluations revealed that 4 weeks of PBOO caused a significant reduction in the electron density of zonula adherens and zonula occludens junctional complexes. Moreover, some desmosomes located between the deeper cells of the uroepithelium showed signs of disintegration. Selective COX-2 inhibitor treatment during 4 weeks of PBOO showed protective effects on adherens and occludens junctions, as well as on desmosomes. Immunohistochemical analysis of E-cadherin confirmed that the decreased E-cadherin immunolabelling in 4 weeks of PBOO was prevented by selective COX-2 inhibitor treatment. Based on ultrastructural morphometrical analysis, we conclude that PBOO alone and in combination with selective COX-2 inhibitors can have considerable effects on uroepithelial cellular junctions. Our findings provide a novel area of investigation regarding the selective use of COX-2 inhibitors following PBOO.
How accurate is measuring postvoid residual volume by portable abdominal ultrasound equipment in peritoneal dialysis patient?
INTRODUCTION: Despite the wide spread use of modern portable ultrasound equipment to measure the postvoid residual urine, its accuracy and reliability has been questioned. We investigated the accuracy of postvoid residual urine measurement by portable abdominal ultrasound equipment in end-stage renal disease patients who are under either hemodialysis or peritoneal dialysis. MATERIALS AND METHODS: A total of 21 male (range: 25-44 years, mean age: 32 years) end-stage renal disease patients were studied. Ten were under peritoneal dialysis and 11 under hemodialysis. After uroflowmetric study, all patients were evaluated with portable abdominal ultrasound equipment (BladderScan BVI 3000, Diagnostic Ultrasound Corporation, WA) by both a technician and a physician and they were subsequently catheterized with a 10F catheter to measure the residual urine volume in the urinary bladder. Postvoid residual urine volume results by portable abdominal ultrasound equipment and urethral catheterization were analyzed. RESULTS: We found portable abdominal ultrasound to be very accurate to measure the volume of postvoid residual urine in hemodialysis patients(r=0.921, P<0.05 by physician and r=0.904, P<0.05 by technician). However, accuracy was the worst in peritoneal dialysis patients (r=0.055, P=0.88 by physician and r=0.336, P=0.343 by technician). The technician or physician use of the equipment did not change the accuracy profile of the equipment in both hemodialysis and peritoneal dialysis patients. CONCLUSIONS: Portable abdominal ultrasound equipment may be an unreliable method to measure postvoid residual urine volume in peritoneal dialysis patients.
Idiopathic prostatic giant calculi in a young male patient.
We report a case of 41-year-old man with idiopathic prostatic giant calculi presenting with voiding difficulty. To our knowledge this is the youngest case with idiopathic prostatic giant calculi reported in the literature. The etiopathogenesis of prostatic calculi are also discussed.
Effect of experimental varicocele on the expressions of Notch 1, 2, and 3 in rat testes: an immunohistochemical study.
OBJECTIVE: To study expressions of Notch receptor isoforms (Notch 1, 2, and 3) in normal and varicocele-induced rat testes to examine their possible functions in cell fate. DESIGN: Comparative and controlled study. SETTING: Animal Care and Operation Unit, Akdeniz University. ANIMAL(S): Wistar male rats for experimental and control groups. INTERVENTION(S): The control group underwent a sham operation (n = 6). The experimental groups underwent partial ligation of the renal vein to induce an experimental varicocele and then were killed 9 (n = 6), 11 (n = 6), and 13 (n = 6) weeks after the induction of varicocele. MAIN OUTCOME MEASURE(S): All tissues were fixed and routinely processed for paraffin embedding. Subsequent immunohistochemical studies were performed. RESULT(S): In the sham-operation rat testes, Leydig cells and elongated spermatids were immunopositive for Notch 1. Notch-2 expression was present in Leydig cells, spermatogonia, and primary spermatocytes. Notch-3 expression was limited to Leydig cells. Varicocele formation diminished the expression of both Notch-1 and Notch-2 receptors as the varicocele formation progressed over time. CONCLUSION(S): The present study suggests that Notch 1 is related to the maturation of spermatids. Notch 2 is related to both proliferation and maturation of spermatogenic cells, whereas Notch 3 seems to be related to Leydig cell functions. The decrease of both Notch-1 and Notch-2 expression depended on the degree of varicocele development over time, indicating a potential role in varicocele-associated testicular dysfunction.
Dynamics of indocyanine green dye in the anterior chamber.
Explore the source record for details and available documents.
Scleral and conjunctival melt caused by a sponge used for topical anesthesia.
Explore the source record for details and available documents.
Should we switch over to tolterodine in every child with non-neurogenic daytime urinary incontinence in whom oxybutynin failed?
OBJECTIVES: To assess the clinical efficacy of tolterodine prescribed to children with non-neurogenic daytime urinary incontinence secondary to overactive bladder who had previously failed to improve with oral oxybutynin treatment and its relation to the side-effect profile and compliance status. METHODS: We evaluated 92 children presenting with daytime wetting, with or without nocturnal enuresis, who were receiving oral oxybutynin treatment. Children with chronic urinary tract infections, a neurologic lesion, an anatomic abnormality of lower urinary tract, voiding abnormality, and less than 1 year of oxybutynin treatment were excluded. Of the remaining 41 children (mean age 7.2 years, range 5 to 14 years), 30 agreed to switch to tolterodine and 11 continued receiving oxybutynin. Anticholinergic side effects, compliance, and clinical efficacy were assessed in the follow-up. RESULTS: Of the 30 patients who switched to tolterodine, a complete response was in 18 patients (60%), partial improvement in 11 (37%), and no improvement in 1 (3%) after a mean of 14.4 months (range 12 to 16 months) of oxybutynin treatment. The anticholinergic side-effect score was 7.2, 9.3, and 11, respectively, for those with a complete response, partial improvement, and no improvement in the compliant group. The noncompliant group had the greatest side-effect score (16.9). The fairly compliant group had a side-effect score of 12.3. After a mean of 7.1 months (range 6 to 9 months) of tolterodine use, a complete response was reported in 24 patients and partial improvement in 5 (17%). In 1 patient, treatment failed completely. However, his side-effect score decreased from 11 to 2. All tolterodine users were compliant with treatment. CONCLUSIONS: The results of this study in children with non-neurogenic daytime urinary incontinence have shown that tolterodine may increase the efficacy of pharmacotherapy, particularly in patients noncompliant to oxybutynin. Additional investigation of the anticholinergic side-effect scores and compliance tables is required to improve the clinical results of pharmacotherapy in incontinence due to overactive bladder in children.
Can alpha-blocker therapy be an alternative to biofeedback for dysfunctional voiding and urinary retention? A prospective study.
PURPOSE: Traditional treatment of dysfunctional voiding in children with urinary retention involves retraining the pelvic floor muscles using biofeedback. Alpha-blockers are reported to also be effective in children with urinary retention and dysfunctional voiding. We compared the efficacy of biofeedback and alpha-blockers for dysfunctional voiding and urinary retention in terms of residual urine volume and urge incontinence episodes, mean flow rates and urinary tract infections. MATERIALS AND METHODS: A total of 28 patients with a mean age of 6.25 years (range 4 to 10) presented with symptoms of urinary incontinence, urgency and urinary tract infections without anatomic and neurogenic causes of urinary retention. All patients had increased post-void residual (PVR) urine volume (mean 59 ml, 32% of age expected capacity [AEC]). The biofeedback group consisted of 16 children (mean age 6.5 years) and the alpha-blocker group consisted of 12 children (mean age 5.9 years). Both groups were also on continued timed voiding, constipation treatment and anticholinergics, which had been used for at least the last 6 months. Biofeedback (median 10, range 6 to 16 sessions) and doxazosin (0.5 to 2 mg) were administered. At 3 and 6 months incontinence episodes, urinary tract infections, mean urinary flow rates, PVR and parental satisfaction grades (1 to 10) were reevaluated. Six refractory cases were started on alpha-blockers and biofeedback, and reevaluated after 1 month and 3 months. RESULTS: Pretreatment mean PVR was 54 ml (30% of AEC), and mean posttreatment PVR was 21 ml (12% of AEC) and 9 ml (5% of AEC) at 3 and 6 months in the biofeedback group (p <0.05). Pretreatment mean PVR was 64 ml (38% of AEC), and posttreatment mean PVR was 17 ml (12% of AEC) and 13 ml (8% of AEC) at 3 and 6 months in the alpha-blocker group (p <0.05). There was no statistical difference in posttreatment PVR between the 2 groups (p >0.05). High PVR persisted in 4 (25%) biofeedback cases and in 2 (16%) alpha-blocker cases. Complete improvement in urge incontinence episodes occurred in 10 (62.5%) and 7 (70%) children in the biofeedback and alpha-blocker groups, respectively. In therapy responsive children parental satisfaction was higher with alpha-blocker than with biofeedback (9.2 vs 7.9, p <0.05). Refractory high PVR decreased significantly after combination treatment with biofeedback and alpha-blocker in 5 of 6 children (mean 80 ml, 35% of AEC vs mean 15 ml, 7% of AEC). No drug related side effect was reported in the alpha-blocker group. CONCLUSIONS: Alpha-blocker therapy seems to be a viable alternative to biofeedback in dysfunctional voiding in children with urinary retention to improve bladder emptying. Combination treatment (biofeedback and alpha-blockers) can be used as additional therapy in refractory cases.
Management of de novo nonneurogenic detrusor-sphincter dyscoordination in a bladder-drained pancreas and kidney transplantation case.
Pancreas transplantation is associated with significant urological complications. Urological complications can jeopardize the graft survival. We present a de novo nonneurogenic detrusor-sphincter dyscoordination in a pancreas and kidney transplanted case. We also report follow-up under conservative treatment.
The restorative effect of a selective cyclooxygenase-2 inhibitor on urothelial cell-cell interactions after partial bladder outlet obstruction in rats.
OBJECTIVE: To determine the changes in cyclooxygenase-2 (COX-2), E-cadherin and alpha-catenin expression after partial bladder outlet obstruction (PBOO), and whether a selective COX-2 inhibitor (celecoxib) might inhibit COX-2 expression and have beneficial effects on urothelial cell-to-cell interactions in rats subjected to PBOO. MATERIALS AND METHODS: Thirty-six male rats were divided into six equal groups; celecoxib was administered after creating PBOO for 1 and 4 weeks in groups 1 and 2, respectively. Two further obstructed groups (3 and 4, PBOO for 1 and 4 weeks, respectively) received no treatment. Sham-operated animals served as controls (group 5 and 6, assessed at 1 and 4 weeks, respectively). After 1 and 4 weeks of PBOO or a sham procedure the bladder weight was recorded before sampling the bladder for Western blotting and immunohistological analysis, to assess the expressions of COX-2 and adherens proteins, E-cadherin and alpha-catenin. Urothelial cell-to-cell interactions were evaluated using electron microscopy. RESULTS: The bladder mass increased rapidly during the first 7 days after PBOO in groups 1-4 compared with 5 and 6 (P < 0.05). While the bladder mass then continued to increase for the next 21 days in group 4, it was constant in group 2 (P < 0.001). Immunohistochemical staining and Western blotting analyses showed that E-cadherin and alpha-catenin expression were reversibly decreased in rats with PBOO, while COX-2 protein expression was up-regulated. After giving celecoxib there was a significant decrease in COX-2 expression and a restoration of intercellular adherens junctions and desmosomes, as assessed on electron microscopy and expression of adherens proteins combined. CONCLUSION: The increase in COX-2 expression attributable to hypoxia and the tensile strength of bladder wall was attenuated by celecoxib. Selective COX-2 inhibitors have important restorative effects on intercellular adherens junctions and desmosomes in PBOO.
The effect of location of the ureteric orifice on the efficacy of endoscopic injection to correct vesico-ureteric reflux.
OBJECTIVE: To review our 11-year experience and identify the mechanisms responsible for the failure of endoscopic injection for vesico-ureteric reflux (VUR) with three different injectable agents, based on the location of the ureteric orifice on endoscopy. PATIENTS AND METHODS: We retrospectively reviewed the charts and endoscopic video-photographs of 46 patients (26 girls, 20 boys, median age 6 years, range 2-16) with VUR treated once or twice by subureteric injection with PTFE, or polydimethylsiloxane or dextranomer/hyaluronic acid copolymer, from 1992 to 2003. Five patients were lost to follow-up and six ectopic and/or duplicated ureters were excluded from the analysis; in all, 52 ureters were analysed. According to the international classification, the VUR was grades I to V in four (8%), 12 (23%), 16 (31%), 13 (25%) and seven (13%) ureters, respectively. RESULTS: After 3 months, voiding cysto-urethrography showed that VUR continued in six of 19, seven of 12 and eight of 21 ureters (38%), respectively, after subureteric PTFE, polydimethylsiloxane and dextranomer/hyaluronic acid copolymer injection; after the second injection, reflux continued in two of six, four of seven and three of eight ureters, respectively. Mound displacement and/or volume loss was the most common failure with all three bulking agents after both the first (62%) and second injections (44%) (P < 0.05). The first injection failed in 32% (11 of 35) normally located ureters and 10 of 17 lateral ureters (P < 0.05). The second injection failed in 11% (four of 35) normal and five of 17 lateral ureters (P < 0.05). CONCLUSIONS: A lateral ureteric orifice may decrease the efficacy of endoscopic injection, as the likelihood of a faulty injection is greater. However, a more careful second injection decreases the failure rate, particularly in those with low- to medium-grade refluxing ureters.
Recent neuroanatomical studies on the neurovascular bundle of the prostate and cavernosal nerves: clinical reflections on radical prostatectomy.
The neurovascular bundle of the prostate and cavernosal nerves have been used to describe the same structure ever since the publication of the first studies on the neuroanatomy of the lower urogenital tract of men, studies that were prompted by postoperative complications arising from radical prostatectomy. In urological surgery every effort is made to preserve or restore the neurovascular bundle of the prostate to avoid erectile dysfunction (ED). However, the postoperative potency rates are yet to be satisfactory despite all advancements in radical prostatectomy technique. As the technology associated with urological surgery develops and topographical studies on neuroanatomy are cultivated, new observations seriously challenge the classical teachings on the topography of the neurovascular bundle of the prostate and the cavernosal nerves. The present review revisits the classical and most recent data on the topographical anatomy of the neurovascular bundle of the prostate and cavernosal nerves and their implications on radical prostatectomy techniques.
Endoscopic treatment of ureteric strictures: acucise, cold-knife endoureterotomy and wall stents as a salvage approach.
OBJECTIVE: To evaluate the factors influencing the results of endoureterotomy using cold-knife and cutting balloon dilatation, and permanent ureteral wall stents in patients with benign ureteral strictures after different operations affecting the ureter. MATERIALS AND METHODS: Over a 4-year period, in 18 patients, endoscopic cold-knife and Acucise endoureterotomies were performed in 13 and 7 renal units, respectively. Eight Memoterm permanent ureteral wall stents were inserted into 7 patients when endoureterotomy failed. Successful outcome was defined by the absence of re-stricture assessed both clinically and radiologically. RESULTS: The strictures were secondary to ureterolithotomy in 6, ureteroscopy in 3, gynecological procedures in 4, abdominal surgeries in 2, transplantation in 2 and continent urinary diversion in 1. The right and left ureters were unilaterally affected in 5 and 11 patients, respectively (5 of them had a solitary kidney), while the remaining 2 patients had bilateral ureteral strictures. We achieved total ureteral patency of 3 (43%) and 7 (54%) renal units with Acucise and cold-knife incision, respectively. Obstructive uropathy was resolved in 6 renal units (75%) of 8 using ureteral wall stents. CONCLUSION: Endoureterotomy with cold-knife or Acucise cutting balloon dilatation is effective in the treatment of iatrogenic ureteral strictures, but only in a selected group. Based on our results, the favorable prognostic criteria for endoureterotomy are the length (< or =1.5 cm), the nonischemic nature of the stricture and adequate renal function. As a salvage approach, permanent self-expanding ureteral wall stents with a 75% success rate may provide a satisfactory outcome for decompression of an obstructed system.
Differential PTEN protein expression profiles in superficial versus invasive bladder cancers.
INTRODUCTION: The prognostic significance of PTEN protein loss in bladder cancer is not well established. The objective of this study was to investigate the PTEN expression profile in superficial noninvasive papillary transitional cell carcinoma (TCC) versus invasive TCC and compared the results with pathological and clinical parameters. MATERIALS AND METHODS: Bladder tumor samples were obtained from 29 patients who underwent surgery for superficial (n=11) and invasive (n=18) bladder cancers at the Akdeniz University Hospital. The patient profile including sex, age, histological grade and the stage, presence of carcinoma in situ, cystoscopy findings (tumor size, location, multiplicity) were obtained by examining the patients' medical records. No patient received anticancer agents prior to the operation. Western blotting was performed using bladder carcinoma samples in order to determine the level of PTEN protein expression for each patient. RESULTS: Only 4 (13.7%) patients with bladder carcinoma manifested a decrease in the level of PTEN expression. Regarding the correlation between tumor stage and the PTEN expression, with the exception of patient 23 all patients who displayed a reduction in PTEN expression had muscle-invasive TCC. CONCLUSION: Future studies with a clinical follow-up will be needed to determine if those superficial tumors with decreased PTEN expression are going to progress to a later stage. Based on our results PTEN by itself does not seem to be a good candidate as an independent marker to predict the behavior of bladder cancers.