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R R Rackley

Publications and source records attributed to R R Rackley.

32 records · Page 2Linked to original sources

In situ anterior vaginal wall sling formation with preservation of the endopelvic fascia for treatment of stress urinary incontinence.

The indications for sling procedures have evolved and encompass patients with either intrinsic sphincteric deficiency (ISD), anatomic incontinence or both. We have refined a technique that can be performed in a minimally invasive fashion with low attendant morbidity to provide a reproducible method of sling formation. Twenty patients with stress urinary incontinence underwent the in situ sling (ISS) with bone fixation. Subsequent evaluation at 24-29 months (mean = 26.2 months) revealed that 95% of patients were cured. No recurrent cystoceles, paravaginal defects or significant detrusor instability have been noted. Urinary retention appeared transiently in only 3 patients and resolved in under 3 weeks. We feel the in situ sling with bone fixation provides a safe and effective means of management for stress urinary incontinence. Furthermore, the reduced surgical dissection may minimize the incidence of postoperative ISD and recurrent paravaginal defects that may accompany more traditional needle suspension procedures.

Female↗

Collagen injection therapy for post-prostatectomy incontinence.

PURPOSE: Post-prostatectomy incontinence has an incidence of 5 to 12% and greatly affects quality of life. Since the approval of glutaraldehyde cross-linked collagen there is a renewed interest in injectable urethral bulking agents. We investigated the long-term efficacy and prognostic criteria for transurethral collagen injection therapy for men with post-prostatectomy incontinence. MATERIALS AND METHODS: From November 1993 to May 1995, 62 men with post-prostatectomy incontinence (54 after radical prostatectomy and 8 after transurethral resection of the prostate) were treated with collagen via a transurethral approach. Median followup was 29.0 months from the date of the last injection procedure. RESULTS: Social continence was defined as dry or minimal leakage requiring at most 1 pad daily with activity. Of 62 patients 38.7% achieved social continence and 8.1% became totally dry. The success rate was 35.2 for radical prostatectomy versus 62.5% for transurethral prostatic resection patients. Of the patients who achieved social continence with at least 1-year followup 23 (60.9%) remained so with no further treatment. At 2-year followup 21 patients (42.8%) maintained social continence. The success rate was 27.3% for those who wore a penile clamp or condom catheter before treatment (3 of 11 patients), and only 21.4% for those who underwent transurethral incision of a bladder neck contracture (3 of 14). A median of 4 injection procedures and 20.0 ml. collagen were required to achieve social continence. CONCLUSIONS: Transurethral collagen injection therapy is a reasonable treatment option for post-prostatectomy incontinence in select patients in whom more conservative therapy has failed. However, patients who have required a penile clamp, experienced continuous leakage or undergone transurethral incision of a bladder neck contracture are unlikely to respond well to this treatment.

Activities of Daily Living↗

Evaluation and medical management of female urinary incontinence.

Urinary incontinence should not be accepted as inevitable, and is not solely the province of urologic specialists. A through history and physical examination, performed by the primary care physician, is the cornerstone of evaluation Most cases respond to behavioral and medical therapy.

Female↗

Collagen injection therapy for female intrinsic sphincteric deficiency.

PURPOSE: Since glutaraldehyde cross-linked collagen was approved for use, studies have reported success or improved rates of 63 to 86%. Long-term efficacy with strictly defined outcome criteria has not been reported. We report our experience with collagen injection therapy for female patients with intrinsic sphincteric deficiency to establish efficacy, duration of response and clinical predictors of success. MATERIALS AND METHODS: A total of 96 women underwent collagen injection via a periurethral approach with local anesthesia. In all patients history, physical examination and video urodynamics documented intrinsic sphincteric deficiency without urethral hypermobility. Continence success was defined as dry or socially continent (minimal leakage requiring 1 or no pad daily even with strenuous activity). Median followup was 14.0 months. RESULTS: Of 94 patients 67.0% achieved continence, 38.3% became dry and 28.7% became socially continent. Of 35 patients who achieved continence with at least 1 year of followup 6 had regression. Therefore, 82.9% of those successfully treated remained so at 1 year and none had de novo detrusor instability. An average of 2.1 procedures and 11.9 ml. collagen were required to achieve continence. The 31 patients not achieving success underwent an average of 3.2 procedures with 16.1 ml. collagen. No major complications have occurred to date. CONCLUSIONS: Collagen injection achieves a reasonable rate of continence and good durability at 1 year of followup in female patients with intrinsic sphincteric deficiency and no urethral hypermobility.

Aged↗

Percutaneous antegrade collagen injection therapy for urinary incontinence following radical prostatectomy.

OBJECTIVES: To determine the potential utility of glutaraldehyde cross-linked collagen (GAX-collagen) administered in an antegrade fashion into the submucosa of the bladder neck in patients who present with postprostatectomy urinary incontinence. METHODS: Twenty-four men aged 59 to 76 years (mean 69.0) with stress type urinary incontinence after radical prostatectomy were evaluated in this study. All patients had previously received retrograde collagen (mean number of treatments 4.33; amount of collagen was 25.72 mL) and had failed to develop further improvement by this approach alone. These patients subsequently received antegrade collagen via a suprapubic approach. An average of 7.1 mL of GAX-collagen was used for the procedure. RESULTS: Minimal follow-up was 12 months (range 12 to 15). Patients were considered cured if they were dry and wore no pads or were socially continent with less than one pad per day. Eighteen of 24 patients (75%) were dry at the 6-month follow-up. With longer follow-up at 12 months, however, only 9 of 24 patients (37.5%) were totally dry. All patients experienced symptomatic improvement as manifested by lower pad usage. CONCLUSIONS: With proper patient selection, antegrade administration of GAX-collagen in patients who have failed standard retrograde collagen injection may salvage many patients from eventual failure of the conservative treatment approach. As newer injectables become available, the overall results may improve.

Aged↗

Testicular cancer in association with developmental renal anomalies and hypospadias.

OBJECTIVES: To characterize the clinical, pathologic, and genetic aspects of patients with a previously undescribed phenotype of testicular germ cell tumors associated with renal hypoplasia or agenesis and urethral hypospadias. METHODS: Review of clinical and pathologic findings and genetic analysis of constitutional and tumor DNA for mutations of the Wilms' tumor suppressor gene (WT1). RESULTS: Clinical findings suggest that this phenotype is distinct from other syndromes associated with renal anomalies and that the associated testicular tumors are histologically and clinically similar to those that occur sporadically. No karyotypic abnormalities, loss of heterozygosity, or mutations in the zinc finger domains (exons 7-10) of WT1 were observed in 5 patients with this phenotype. CONCLUSIONS: The phenotype of testicular germ cell tumor, developmental renal anomalies, and urethral hypospadias constitutes a discrete syndrome caused by a gene distinct from WT1.

Adult↗

Vesica percutaneous bladder neck stabilization.

The Vesica percutaneous bladder neck stabilization (PBNS) represents a minimally invasive surgical procedure for the treatment of stress incontinence caused by hypermobility of the proximal urethra and bladder neck. Since the initial description of the procedure, technique and instrumentation modifications have added to the reproducibility of this operation. Three specific modifications have been incorporated: strong attachment of the stabilization suture to the pubic bone utilizing a bone anchor; incorporation of a full-thickness broad segment of tissue including the endopelvic, pubocervical, and subvaginal fascia as well as vaginal wall in a Z suture; and loose resuspension of the proximal urethra to stabilize the continence mechanism. Cystoscopic verification of suture location precludes bladder entry or distal suture placement. This procedure has been utilized in 71 women with an overall cure rate (no stress incontinence) of 94% at follow-up of 12 months. One retropubic abscess required drainage, and a second patient required excision of a skin sinus tract caused by an infected bone anchor. Urinary retention longer than 3 weeks has not been encountered. Overall morbidity has been minimal. Long-term follow-up of continence status and other procedure-related complications is ongoing. The PBNS provides continence results and complication rates equivalent to those of other retropubic and transvaginal procedures using a minimally invasive outpatient technique.

Endoscopy↗

In situ expression of the early growth response gene-1 during murine nephrogenesis.

WT1 maps to chromosome 11p13 and encodes a deoxyribonucleic acid (DNA) binding protein whose expression is necessary for normal urogenital development. The WT1 protein binds to some of the same DNA sequences as the early growth response gene-1 (EGR-1) protein, the latter being an immediate-early gene product that activates or represses transcription in a promoter and cell-specific manner. Transient transfection experiments have shown that WT1 can repress EGR-1 activated transcription from the EGR-1 promoter. To determine if WT1 is likely to be a physiologically important repressor of EGR-1 we performed ribonucleic acid (RNA) in situ hybridization of EGR-1 on sequential sagittal sections of murine embryos before and throughout nephrogenesis, and compared the results to our previous study of WT1 expression during murine embryogenesis. Prior to embryological day 9.5 WT1 messenger RNA expression is absent in the embryo proper but is expressed in the maternal uterus. With the initiation of organogenesis on embryological day 10.5 WT1 messenger RNA localizes within the pronephric and mesonephric tissues. By embryological day 11.5 the nephrogenic cord, urogenital ridge and metanephric tissue have WT1 hybridization signals and increasingly centripetal expression of WT1 in the kidney correlates with differentiation from embryological days 11.5 to 16.5. In contrast to previous reports of the tissue restricted expression of WT1, EGR-1 expression by in situ hybridization was apparent in all 3 germ layers and their derivatives throughout embryogenesis. Down-regulation of EGR-1 expression occurred in the maternal uterus as well as the metanephric blastema and its derivatives during renal development. This observation defines a spatial and temporal window during which WT1 competition for EGR-1 DNA binding sites may be involved in regulating EGR-1 expression.

Animals↗

Expression of the Von Hippel-Lindau tumor suppressor gene, VHL, in human fetal kidney and during mouse embryogenesis.

BACKGROUND: Von Hippel-Lindau (VHL) disease is a familial cancer syndrome that has a dominant inherited pattern which predisposes affected individuals to a variety of tumours. The most frequent tumors are hemangioblastomas of the central nervous system and retina, renal cell carcinoma (RCC), and pheochromocytoma. The recent identification and characterization of the VHL gene on human chromosome 3p and mutational analyses confirms the VHL gene functions as a classical tumor suppressor. Not only are mutations in this gene responsible for the VHL syndrome, but mutations are also very frequent in sporadic RCC. MATERIALS AND METHODS: VHL expression in human kidney and during embryogenesis, was analyzed by in situ mRNA hybridization with 35S-labeled antisense VHL probes, derived from human and mouse cDNAs, on cryosections of human fetal kidney and paraffin sections of murine embryos. RESULTS: In human fetal kidney, there was enhanced expression of VHL within the epithelial lining of the proximal tubules. During embryogenesis, VHL expression was ubiquitous in all three germ cell layers and their derivatives. Expression occurred in the cerebral cortex, midbrain, cerebellum, retina, spinal cord, and postganglionic cell bodies. All organs of the thoracic and abdominal cavities expressed VHL, but enhanced expression was most apparent in the epithelial components of the lung, kidney, and eye. CONCLUSIONS: In human fetal kidney, the enhanced epithelial expression of the VHL gene is consistent with the role of this gene in RCC. There is widespread expression of the VHL gene during embryogenesis, but this is pronounced in areas associated with VHL phenotypes. These findings provide a histological framework for investigating the physiological role of the VHL gene and as basis for further mutational analysis.

Animals↗

Renal cell carcinoma arising in a regressed multicystic dysplastic kidney.

Controversy surrounds the management of multicystic dysplastic kidney. Recent advances in radiological imaging have resulted in a higher incidence of its detection, and they provide an accurate noninvasive means of diagnosis and followup. Consequently, the need for surgical removal of these lesions is being reevaluated. We report a case of renal cell carcinoma arising from solid renal dysplasia associated with a regressed multicystic dysplastic kidney. We emphasize the potential risk of nonoperative management of these lesions and further define the spectrum of malignant degeneration associated with renal dysplasia.

Adolescent↗

Expression of the Wilms' tumor suppressor gene WT1 during mouse embryogenesis.

WT1 is a Wilms' tumor suppressor gene that maps to human chromosome 11p13 and encodes a putative transcription factor implicated in controlling normal urogenital development. Sporadic homozygous mutations in WT1 result in the development of Wilms' tumor (nephroblastoma), and heterozygous germline mutations can give rise to a phenotype which includes nephropathy and urogenital abnormalities (the Denys-Drash syndrome). Thus, inappropriate expression of WT1 results in developmental abnormalities affecting the urogenital system. To better define the temporal and spatial distribution of WT1 expression during embryogenesis, we have used in situ mRNA hybridization and immunohistochemistry to examine WT1 expression in murine embryos during the period prior to and throughout active organogenesis. Prior to embryological day 9.5 (E9.5), WT1 mRNA expression is absent in the embryo proper but is strongly expressed in the maternal uterus. During the initiation of organogenesis on E10.5, WT1 mRNA is localized within the pronephric and mesonephric tissues. By E11.5, the nephrogenic cord, urogenital ridge, and condensing metanephric tissue show intense WT1 hybridization signals, and increasingly centripetal expression of WT1 in the kidney correlates with renal differentiation from days E11.5 through E16.5. The stromal cell components in the developing gonad show expression of WT1 by E10.5, whereas in the remaining organs examined, WT1 expression is restricted to the uterus, spleen, abdominal wall musculature, and mesothelial lining of organs within the thoracic and abdominal cavities. Interestingly, there is also WT1 expression in the central nervous system which localizes to the ependymal layer of the ventral aspect of the spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differences in the leucine aminopeptidase activity in extracts from human prostatic carcinoma and benign prostatic hyperplasia.

Extracts of tissue showed that prostatic carcinomas contain less leucine aminopeptidase activity than benign prostatic hyperplasia. This is true when activity is expressed as specific activity (P = 0.0033), specific activity/% epithelium (P = 0.0007), activity/wet weight of tissue (P = 0.0028), or activity/wet weight of tissue/% epithelium (P = 0.0005). Almost all histochemically demonstrable activity is located in the epithelium. Enzymatic activities in extracts and in histochemical preparations showed similar differences between carcinoma and benign prostatic hyperplasia and were related (R = -0.38, P = 0.0400) to Gleason's grades. The transurethrally resected prostate cancers studied contained no well-differentiated tumors and a high proportion of poorly differentiated tumors. Histochemical activity is absent in most prostatic carcinomas and decreased in others. This observation is particularly interesting in view of the growing knowledge of tumor suppressor genes.

Aged↗

Enzymatic activities in extracts of small (20 +/- 5 mg) samples of prostatic carcinoma.

Previously, we reported that the activities of several enzymes extracted from prostatic cancers were closely related to the histologic grades (Gleason's grades) of the cancers. The survival of patients was more closely correlated with certain enzymatic activities than with Gleason's grades. Unfortunately, because our assays required relatively large amounts of tissue, the increasing proportion of patients who have needle biopsies as their only surgical procedure had to be excluded from our previous study. We now report a method that permits multiple enzyme assays to be carried out with much smaller amounts of tissue. This method will enable us to avoid the selection inherent in the exclusion of patients who have only needle biopsies and should permit the prospective study of most patients with prostatic carcinoma.

Arginase↗

5'-nucleotidase activity in prostatic carcinoma and benign prostatic hyperplasia.

In light of previous reports of alterations in 5'-nucleotidase activity in neoplastic conditions, 5'-nucleotidase activity was examined histochemically in tissue sections and quantified biochemically in extracts of human hyperplastic prostates and prostatic carcinomas obtained surgically. The 5'-nucleotidase activities per mg protein in extracts of 29 prostatic carcinomas were lower (P less than 0.0005) than in extracts from 10 samples of benign prostatic hyperplasia. The 5'-nucleotidase activity per mg protein in extracts of prostatic carcinoma from the 29 patients correlated (R = -0.369, P = 0.049) with the degree of histological differentiation; the extracts of poorly differentiated carcinomas contained low levels of 5'-nucleotidase. When age and histological differentiation (Gleason's grade) were adjusted, the enzyme activity per mg protein correlated (R = 0.242, P = 0.004) with patient survival. When all three parameters were considered together, i.e., histological grade of the tumor, 5'-nucleotidase extracted from the tumor, and age of the patient, they were found to be mutually complementary for the prediction of patient survival (R = 0.388, P = 0.0001). To our knowledge, this is the first report that prostatic epithelium expresses 5'-nucleotidase; further work will be required to define the reasons for the high levels of activity observed in prostates without cancer and for the decrease in the activity in prostatic carcinoma.

5'-Nucleotidase↗