Biomedical subjects
Publications and source records attributed to Mark L Gonzalgo.
We have experienced the inability to remove silicone Foley catheters even after complete deflation of the balloon. This potential complication can result from cuffing of the catheter balloon. We present a description of this phenomenon and approaches for successful management of a Foley catheter that has become entrapped due to balloon cuffing.
The presence of a foreign body in the genitourinary tract represents a urologic challenge that often requires prompt intervention. We describe an endoscopic approach that was used for removal of a foreign body located in the prostatic urethra of a schizophrenic man. A nitinol stone basket was used as an effective means for extraction of a large metal screw from the urethra of this patient.
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PURPOSE: We assessed the long-term clinical efficacy of sildenafil citrate (SC) and predictors of satisfactory outcome. MATERIALS AND METHODS: All patients were evaluated with a self-administered questionnaire or by telephone interview before, and 3 months and 2.5 years following the initiation of SC therapy. Current SC use, other therapies and overall level of sexual satisfaction were assessed. Sexual function was measured using an abbreviated version of the International Index of Erectile Function questionnaire. RESULTS: Of the 197 men 97 (49%) were using SC at 2.5 years. Patients with a history of diabetes mellitus or prostate surgery were least likely to be satisfied with SC therapy. Men with vasculogenic etiologies for erectile dysfunction were more likely to be on SC and had better sexual function scores at 2.5 years than men with a history of prostate surgery. The 3-month International Index of Erectile Function questionnaire score was an excellent predictor of sexual satisfaction in men who continued to use SC at 2.5 years. Of the 100 men who discontinued treatment with SC 56% chose not to pursue any other treatment. CONCLUSIONS: SC remains a highly effective and durable oral agent for erectile dysfunction. Improved sexual function and sexual satisfaction were well maintained 2.5 years following the initiation of SC therapy, especially in patients with vasculogenic or psychogenic etiologies of erectile dysfunction. Patients who discontinued SC reported significantly decreased sexual function than their counterparts but under used alternative therapies to improve erectile dysfunction.
PURPOSE: We assess the feasibility of a urinary test for prostate cancer detection in a high-risk patient cohort based on methylation-specific PCR analysis of the pi class glutathione S-transferase (GSTP1) gene promoter. EXPERIMENTAL DESIGN: A total of 45 men underwent transrectal ultrasound-guided biopsy of the prostate for suspected malignancy. Clean-catch voided urine specimens were prospectively collected from each patient immediately after biopsy. Genomic DNA was isolated from urine specimens and subjected to sodium bisulfite modification. Methylation of the GSTP1 promoter was examined in a blinded manner by methylation-specific PCR analysis and correlated with pathology results, and clinical information was obtained from the patient record. RESULTS: Methylation of GSTP1 in the urine was detected in a total of 18 of 36 (50%) informative cases. A total of 7 of 18 (39%) patients with prostate adenocarcinoma identified on their initial biopsy had detectable urinary GSTP1 methylation (58% sensitivity among informative cases). Abnormal urinary GSTP1 methylation was also detected in 7 of 21 (33%) patients without evidence of cancer on biopsy and in 4 of 6 (67%) patients diagnosed with atypia or high-grade prostatic intraepithelial neoplasia. CONCLUSIONS: We have demonstrated the feasibility of a novel, noninvasive molecular approach for the detection of epigenetic changes associated with prostate cancer. A screening test based on GSTP1 methylation in the urine specimens of patients with suspected prostate malignancy may be a useful adjunct to serum screening tests and digital rectal examination findings for identification of men at increased risk of harboring cancer despite a negative biopsy. This molecular assay has potential application for stratification of patients into low- and high-risk groups for surveillance versus repeat biopsy.
Methylation-sensitive single-nucleotide primer extension (Ms-SNuPE) is a technique that allows for rapid and simultaneous quantitation of the degree of methylation at several CpG sites. Treatment of genomic DNA with sodium bisulfite is used to convert unmethylated cytosine to uracil while leaving 5-methylcytosine unchanged. A strand-specific polymerase chain reaction product is then generated to provide a suitable DNA template for quantitative methylation analysis using Ms-SNuPE. Single-nucleotide primer extension is performed with oligonucleotide(s) designed to hybridize immediately upstream of the CpG site(s) being analyzed. The Ms-SNuPE technique can be adapted for high-throughput methylation analysis and therefore represents a novel approach for rapid quantitation of cytosine methylation suitable for a wide range of biological investigations.
The ability to detect methylation changes associated with oncogenic transformation is of critical importance in understanding how DNA methylation may contribute to tumorigenesis. We have developed a simple and reproducible fingerprinting method called methylation-sensitive arbitrarily primed polymerase chain reaction (AP-PCR) to screen for DNA methylation changes. This technique relies on digesting genomic DNA with methylation-sensitive and -insensitive restriction enzymes (e.g., HpaII and MspI) prior to AP-PCR amplification. Matched normal and tumor DNAs were compared to identify differential methylation. After the PCR products were resolved on high-resolution polyacrylamide gels, regions of genomic DNA that showed hypo- and hypermethylation associated with tumors were detected. These fragments were then isolated, cloned, and sequenced. Novel CpG islands were found to be frequently hypermethylated in bladder and colon tumors. We have demonstrated that this technique is a rapid and efficient method that can be used to screen for altered methylation patterns in genomic DNA and to isolate specific sequences associated with these changes.
PURPOSE: We evaluated the postoperative clinical course of patients with renal cancer identified preoperatively by microsatellite analysis to examine the correlation between microsatellite alterations and risk of disease recurrence and patient mortality 2 years after nephrectomy. EXPERIMENTAL DESIGN: A panel of 28 microsatellite markers was used previously to assess loss of heterozygosity and microsatellite instability in urine, serum, and tumor DNA of 30 patients with clinically organ-confined renal masses who underwent partial or radical nephrectomy. The clinical reports and imaging data in the medical records of patients with a minimum follow-up of 2 years were retrospectively reviewed to determine their postoperative course. RESULTS: Two-year follow-up was available for the 30 patients (100%) who entered the study. Mean age was 61.6 +/- 12.9 years (range, 21-77 years). Tumor stage was associated with patient mortality (P = 0.03). Tumor grade was associated with mortality (P = 0.03) and disease recurrence (P < 0.01). The frequency of microsatellite alterations (loss of heterozygosity) found in the preoperative serum of patients with renal masses served as a prognostic indicator for disease recurrence (P < 0.01). CONCLUSIONS: Analysis of microsatellite alterations found in preoperative blood samples is a promising method for the detection of renal cancer. The presence of frequent molecular changes in preoperative serum was associated with disease recurrence. These findings suggest a role for microsatellite analysis in future studies attempting to stratify patients with clinically organ-confined renal cancer into low- and high-risk prognostic groups. Larger prospective randomized trials are needed to validate the clinical utility of this observation.