Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders.

Biomarkers are needed to assist in the diagnosis and medical management of various neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy body (DLB). We have employed a multiplex quantitative proteomics method, iTRAQ (isobaric Tagging for Relative and Absolute protein Quantification), in conjunction with multidimensional chromatography, followed by tandem mass spectrometry (MS/MS), to simultaneously measure relative changes in the proteome of cerebrospinal fluid (CSF) obtained from patients with AD, PD, and DLB compared to healthy controls. The diagnosis of AD and DLB was confirmed by autopsy, whereas the diagnosis of PD was based on clinical criteria. The proteomic findings showed quantitative changes in AD, PD, and DLB as compared to controls; among more than 1,500 identified CSF proteins, 136, 72, and 101 of the proteins displayed quantitative changes unique to AD, PD, and DLB, respectively. Eight unique proteins were confirmed by Western blot analysis, and the sensitivity at 95% specificity was calculated for each marker alone and in combination. Several panels of unique makers were capable of distinguishing AD, PD and DLB patients from each other as well as from controls with high sensitivity at 95% specificity. Although these preliminary findings must be validated in a larger and different population of patients, they suggest that a roster of proteins may be generated and developed into specific biomarkers that could eventually assist in clinical diagnosis and monitoring disease progression of AD, PD and DLB.

Efficacy of shunt surgery for refractory low flow priapism: a report on the incidence of failed detumescence and erectile dysfunction.

PURPOSE: The reported success rate for surgical cavernosa-to-spongiosum shunts in patients with refractory low flow priapism is variable and yet it is reported to be as high as 100% in terms of achieving detumescence. The long-term potency rate after the introduction of the shunt procedure is also as high as 50%. We reviewed the efficacy of various shunts in terms of achieving detumescence and we clarified the rate of erectile dysfunction at long-term followup. MATERIALS AND METHODS: Patients were included in the analysis if they had painful low flow priapism more than 4 hours in duration that was refractory to conservative management, ultimately requiring a surgical shunt. Data, including etiology, duration and initial treatment measures, were retrospectively compiled in the last 12 years and the type of surgical shunts performed were recorded. Followup erectile function was assessed by clinical notes and a telephone survey using the International Index of Erectile Function. RESULTS: Of the 28 consecutive patients included in the study 13 (46.4%) required more than 1 operation for failed detumesence, of whom 12 (92.3%) initially underwent a Winter shunt. Only 2 of the 20 men (10%) with available followup reported preservation of pre-morbid erectile function. Three men (15%) achieved partial erection without the assistance of oral or injectable agents. CONCLUSIONS: In contrast to previously reported success rates, approximately 50% of our patients required reoperation for failed detumescence following a cavernosa-to-spongiosum shunt. In our experience the Winter shunt was the least successful operation, whereas reoperation was uncommonly required following an Al-Ghorab or Quackels shunt. As many as 90% of our patients had erectile dysfunction at followup.

Laparoscopic variability of the internal inguinal ring: review of anatomical variation in children with and without a patent processus vaginalis.

PURPOSE: Diagnostic laparoscopy is routinely performed at our institution in children with a unilateral inguinal hernia to determine whether the contralateral processus vaginalis is patent. We reviewed the anatomical variability of the inguinal ring at laparoscopy in children with and without a hernia in various age groups. MATERIALS AND METHODS: Since 1992, we have performed diagnostic laparoscopy in more than 1,500 children with a known inguinal hernia. Intraoperative imaging was correlated with clinical and operative findings to characterize the anatomical variability of the internal ring. RESULTS: The internal ring had many variations. The photographs presented show evidence of the progression from the flat closed ring to the widely open sac. Clefts and veils of peritoneum sometimes made determining the exact anatomy difficult. Experience shows that the various anatomical variations are associated with different pathological conditions. CONCLUSIONS: Characterization of the anatomical variability of the internal ring is essential for determining the patency of the processus vaginalis at diagnostic laparoscopy in children with a known inguinal hernia. We classified these variations in accordance with clinical and surgical findings.

Carcinoma in situ and tumor multifocality predict the risk of prostatic urethral involvement at radical cystectomy in men with transitional cell carcinoma of the bladder.

PURPOSE: Determining which patients are at risk for prostatic urethral involvement of urothelial carcinoma may alter assessment of the prostatic urethra before radical cystectomy and ultimately influence the choice of urinary diversion. We determined risk factors predictive of prostatic urethral involvement using preoperative bladder tumor characteristics in male patients who underwent radical cystoprostatectomy due to urothelial carcinoma of the bladder. MATERIALS AND METHODS: We reviewed 192 consecutive radical cystectomy specimens from men with transitional cell carcinoma from June 1995 to June 2000. The prostatic urethra in each specimen was analyzed and urethral involvement was characterized as carcinoma in situ, intraductal invasion or prostatic stromal invasion. We then examined which clinical bladder tumor characteristics correlated with the incidence and extent of prostatic urethral involvement by performing multiple variable analysis. RESULTS: Prostatic urethral involvement was evident in 30 of the 192 patients (15.6%). Of the 80 patients with carcinoma in situ in the bladder 25 (31.3%) had concomitant prostatic urethral involvement with carcinoma, whereas only 5 (4.5%) of the 112 with no evidence of carcinoma in situ had prostatic urethral involvement. Likewise 25 of the 72 patients (34.7%) with multifocal tumors had concomitant prostatic urethral involvement with carcinoma, whereas only 5 (4.2%) of the 120 with no evidence of multifocality had prostatic urethral involvement. In the multiple variable logistic regression model the odds of prostatic urethral involvement were 12 and 15-fold greater when carcinoma in situ and tumor multifocality were present, respectively. CONCLUSIONS: Carcinoma in situ and/or tumor multifocality are valuable prognostic indicators of prostatic urethral involvement. However, in their absence prostatic urethral involvement was rare. Ultimately the extent of prostatic urethral involvement may influence decisions, such as the choice of urinary diversion and need for urethrectomy, in men undergoing radical cystectomy.