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Biomedical subjects

R G Uzzo

Publications and source records attributed to R G Uzzo.

34 records · Page 2Linked to original sources

Mechanisms of apoptosis in T cells from patients with renal cell carcinoma.

Tumors may escape immune recognition and destruction through the induction of apoptosis in activated T lymphocytes. Results from several laboratories suggest that FasL (L/CD95L) expression in tumors may be responsible for this process. In this study of patients with renal cell carcinoma (RCC), we provide evidence for two mechanisms of T-cell apoptosis. One mechanism involves the induction of apoptosis via FasL expression in tumor cells. This is supported by several observations, including the fact that tumor cells in situ as well as cultured cell lines expressed FasL mRNA and protein by a variety of techniques. The FasL in RCC is functional because in coculture experiments, FasL+ tumors induced apoptosis in Fas-sensitive Jurkat T cells and in activated peripheral blood T cells but not in resting peripheral blood T cells. Most importantly, antibody to FasL partially blocked apoptosis of the activated T cells. Moreover, Fas was expressed by T cells derived from the peripheral blood (53% median) and tumor (44.3% median) of RCC patients. Finally, in situ staining for DNA breaks demonstrated apoptosis in a subset of T cells infiltrating renal tumors. These studies also identified a second mechanism of apoptosis in RCC patient peripheral T cells. Whereas these cells did not display DNA breaks when freshly isolated or after culture for 24 h in medium, peripheral blood T cells from RCC patients underwent activation-induced cell death after stimulation with either phorbol 12-myristate 13-acetate/ionomycin or anti-CD3/CD28 antibodies. Apoptosis mediated by exposure to FasL in tumor cells or through T-cell activation may contribute to the failure of RCC patients to develop an effective T-cell-mediated antitumor response.

Apoptosis↗

Use of a free bladder mucosal graft for simple repair of vesicovaginal fistulae.

The aim of this paper is to describe a simple, fast, and effective method for repair of difficult vesicovaginal fistulae by means of a free bladder mucosal graft. Six patients with high, large, multiple, or recurrent vesicovaginal fistulae were treated using a free bladder mucosal graft. Three patients underwent "early" repair (less than 3 months from time of injury) and 3 "late" repair (more than 6 months from time of injury). Via a suprapubic cystotomy, the mucosa of the fistulous tract was debrided without any attempt to excise the tract or close the bladder or vaginal defects. A free bladder mucosal graft was harvested from an unaffected portion of the bladder and placed over the fistulous tract, and mucosal approximation was made using interrupted 5-0 chromic stay sutures. The donor urothelial defect was allowed to re-epithelialize. A Foley catheter, suprapubic tube, and vaginal packing were left in place. Five patients noted an immediate result, with no evidence of leakage, and the suprapubic tube was removed by week 3. One patient required prolonged catheter drainage, and the tube was successfully removed by week 6. This patient had undergone irradiation. All patients remain dry at follow-up, which ranges from 2 to 6 years. We describe a simple and effective method for transabdominal vesicovaginal fistula repair, involving minimal mobilization, decreased dissection, and no need for rotational or interposition flaps, obviating the need to open the peritoneum. A free bladder mucosal graft can be used regardless of the individual anatomy or proximity to the ureteral orifices, because it can easily be tailored. This technique represents an important repair of difficult, recurrent, or multiple vesicovaginal fistulae.

Female↗

Microsurgical repair of the adolescent varicocele.

PURPOSE: Since clinically apparent varicoceles may affect testicular volume and sperm production, early repair has been advocated. However, repair of the pediatric varicocele with conventional nonmagnified techniques may result in persistence of the varicocele after up to 16% of these procedures. Also testicular artery injury and postoperative hydrocele formation can occur after nonmagnified repair. The microsurgical technique has been successfully completed in a large series of adults with a dramatic reduction in complication and recurrence rates. We report our experience with the microsurgical technique in boys. MATERIALS AND METHODS: A total of 30 boys (average age 15.9 years) underwent 42 microsurgical varicocelectomies (12 bilateral). All patients had a large left varicocele. Indications for repair included testicular atrophy (size difference between testicles of greater than 2 ml.) in 20 boys, pain in 5 and a large varicocele without pain or testicular atrophy in 5. Six boys were referred following failure of conventional nonmicrosurgical techniques. All boys were examined no sooner than 1 month postoperatively (mean followup 12). RESULTS: Preoperative volume of the affected testis averaged 13.0 ml., and an average size discrepancy between testicles of 2.8 ml. was noted before unilateral varicocelectomy. No cases of persistent or recurrent varicoceles were detected, and 1 postoperative hydrocele resolved spontaneously. After unilateral varicocelectomy the treated testes grew an average of 50.1%, while the contralateral testes grew only 23%. Overall, 89% of patients with testicular atrophy demonstrated reversal of testicular growth retardation after unilateral varicocelectomy. In contrast, both testes showed similar growth rates after bilateral varicocelectomy (45% left testis, 39% right testis). CONCLUSIONS: The meticulous dissection necessary to preserve arterial and lymphatic supply, and to ligate all spermatic veins in the pediatric patient is readily accomplished using a microsurgical approach, and results in low recurrence and complication rates. Rapid catch-up growth of the affected testis after microsurgical varicocelectomy suggests that intervention during adolescence is effective and warranted.

Adolescent↗

Laparoscopic surgery in children with ventriculoperitoneal shunts: effect of pneumoperitoneum on intracranial pressure--preliminary experience.

OBJECTIVES: We monitored changes in intracranial pressure (ICP) in 2 children with myelodysplasia undergoing laparoscopic bladder autoaugmentation. Both children had ventriculoperitoneal shunts (VPS) secondary to Arnold-Chiari malformations (type II). METHODS: ICP was monitored through a 23-gauge needle placed into the shunt reservoir and connected to a pressure transducer and drainage system. Intraoperative mean arterial pressure, end-tidal CO2 (ETCO2), ICP, abdominal pressure, and cerebral perfusion pressures were all monitored. RESULTS: Both children demonstrated rapid onset and sustained increases in ICP of greater than 12 mm Hg above baseline to a maximum pressure of 25 mm Hg. The average cerebrospinal fluid removed from each patient was 30 cc, thereby lowering ICP with no adverse neurologic sequela. The pCO2 remained constant throughout the procedures, as measured by ETCO2. CONCLUSIONS: We believe that intracranial hypertension (IH) results from a "Valsalva-like" phenomenon, which causes cerebral vascular engorgement. In addition, the pneumoperitoneum may increase the resistance to outflow through the distal peritoneal catheter, causing a partial or complete shunt obstruction. Untreated IH may result in adverse neurologic sequelae from brain herniation in these children with hindbrain anomalies and potentially altered brain compliance. We believe it is prudent to perform intraoperative ICP monitoring in this subgroup of patients undergoing laparoscopic surgery and that IH should be treated by ventricular drainage.

Child↗

Laparoscopic laser assisted auto-augmentation of the pediatric neurogenic bladder: early experience with urodynamic followup.

PURPOSE: We report our initial experience with laparoscopic laser assisted bladder auto-augmentation for treatment of the symptomatic pediatric neurogenic bladder. MATERIALS AND METHODS: Laparoscopic auto-augmentation of the bladder was performed in 2 children with myelodysplasia and high pressure neurogenic bladders unresponsive to medical management. Detrusorotomy was done using the KTP-532 laser. Laser energy was directed to the tissue to evaluate long-term effects of the procedure. RESULTS: Laparoscopic bladder auto-augmentation can be performed easily and with less morbidity compared to open auto-augmentation. Although results at 6 weeks showed improvement, enterocystoplasty was ultimately performed in both cases due to symptomatic recurrence of incontinence associated with increasing peak detrusor pressure and decreasing compliance. CONCLUSIONS: While this technique has the potential to offer minimally invasive correction in patients with low capacity, high pressure bladders, further modifications will be required to achieve long-term success.

Child↗

Laser tissue welding in genitourinary reconstructive surgery: assessment of optimal suture materials.

OBJECTIVES: Laser tissue welding in genitourinary reconstructive surgery has been shown in animal models to decrease operative time, improve healing, and decrease postoperative fistula formation when compared with conventional suture controls. Although the absence of suture material is the ultimate goal, this has not been shown to be practical with current technology for larger repairs. Therefore, suture-assisted laser tissue welding will likely be performed. This study sought to determine the optimal suture to be used during laser welding. METHODS: The integrity of various organic and synthetic sutures exposed to laser irradiation were analyzed. Sutures studied included gut, clear Vicryl, clear polydioxanone suture (PDS), and violet PDS. Sutures were irradiated with a potassium titanyl phosphate (KTP)-532 laser or an 808-nm diode laser with and without the addition of a light-absorbing chromophore (fluorescein or indocyanine green, respectively). A remote temperature-sensing device obtained real-time surface temperatures during lasing. The average temperature, time, and total energy at break point were recorded. RESULTS: Overall, gut suture achieved significantly higher temperatures and withstood higher average energy delivery at break point with both the KTP-532 and the 808-nm diode lasers compared with all other groups (P < 0.05). Both chromophore-treated groups had higher average temperatures at break point combined with lower average energy. The break-point temperature for all groups other than gut occurred at 91 degrees C or less. The optimal temperature range for tissue welding appears to be between 60 degrees and 80 degrees C. CONCLUSIONS: Gut suture offers the greatest margin of error for KTP and 808-nm diode laser welding with or without the use of a chromophore.

Evaluation Studies as Topic↗

Use of a catheter limiter during intermittent catheterization.

We report on the use of a new device, the catheter limiter, to facilitate clean intermittent catheterization. The device limits the length of catheter entering the urethra. This provides a means to reduce the risk of mechanical injury and perforation, minimizes incomplete emptying, and improves safety and patient acceptance of intermittent catheterization.

Equipment Design↗

The influence of prostate size on cancer detection.

OBJECTIVES: To determine if cancer detection rates vary with prostate size using a sextant core biopsy pattern. METHODS: We reviewed 1021 transrectal ultrasound (TRUS)-guided sextant pattern prostate biopsies to determine if cancer detection varied based on prostate size. Prostate size was determined using a computer generated elliptical estimation method. Sextant core biopsies were taken, and the patients divided into groups based on estimated size of the prostate and biopsy outcome. Large prostates were those that were estimated by TRUS as 50 cc or more. Prostates were considered small if they were less than 50 cc. Groups were compared based on size and biopsy outcome. RESULTS: Adenocarcinoma was detected in 33% (334 of 1021) of the patients. Large prostates were noted in 34% (346 of 1021), of which 23% (80 of 346) had cancer detected by sextant biopsy. Small prostates were noted in 66% (675 of 1021), of which 38% (254 of 675) had cancer detected. The difference in cancer detection in large and small glands using a sextant pattern was statistically significant (P < 0.01). Patients with positive biopsies had significantly smaller prostate sizes (40 cc +/- 26) when compared with those with negative biopsies (51 cc +/- 33) (P < 0.01). Only 14% (8 of 58) of patients with gland sizes 100 cc or greater had positive sextant biopsies while 49% (118 of 239) with prostates 25 cc or less had cancer detected. Multivariate statistical analysis was used to control for differences in age, prostate-specific antigen (PSA), PSA density, TRUS findings, and digital rectal examination between the large and small prostate groups. The difference in cancer detection persisted (P < 0.05) CONCLUSIONS: Currently no evidence exists to support differing cancer rates based on gland size alone. Our cancer detection rate using a sextant pattern was higher in men with prostates less than 50 cc, and patients diagnosed with cancer had significantly smaller prostates than those with a negative sextant biopsy. Our data suggest that significant sampling error may occur in men with large glands, and more biopsies may be needed under these circumstances. The effects of tumor volume, focality, and specimen size in relation to overall gland size may contribute to these findings.

Adenocarcinoma↗

Biopsy of lesions of the male genitourinary tract.

Biopsy of benign and malignant lesions of the male genitourinary tract using a variety of open and endourologic techniques is possible. A multidisciplinary approach involving close communication between clinicians, radiologists, and pathologists is imperative to a favorable outcome. Urologic practice has pioneered many of these techniques, which continue to evolve as new technologies become available.

Adrenal Gland Neoplasms↗

Genitourinary reconstructive surgery utilizing laser tissue welding.

Laser tissue welding contributes several distinct advantages over current tissue approximation methods in the genitourinary tract. Low level laser energy combined with a protein solder can provide an immediate watertight seal that is supraphysiologic, nonlithogenic, rapid, and reliable. This review highlights the history of laser tissue welding, its applications to urologic surgery, recent developments to improve the technique, and future directions.

Animals↗

An unusual cause of duodenal obstruction: ureteropelvic junction obstruction and the renoalimentary relationship.

Ureteropelvic junction obstruction may present with a variety of urologic and gastrointestinal complaints. The constellation of symptoms is most often attributed to shared visceral pathways. In cases of giant hydronephrosis, mechanical obstruction of the gastric outlet or duodenal sweep may play an additional role in presentation. We present an unusual case of duodenal obstruction caused by ureteropelvic junction stenosis. The anatomic and autonomic renoalimentary relationships are reviewed.

Adult↗

Captopril renography in the diagnosis of renal artery stenosis: accuracy and limitations.

PURPOSE: The purpose of this study was to determine the sensitivity, specificity, and clinical usefulness of renography performed in combination with captopril administration ("captopril renography") in diagnosing renal artery stenosis. PATIENTS AND METHODS: Fifty-five patients with suspected renal artery stenosis underwent renography prior to performance of renal angiography. Renography was performed on two consecutive days using technetium-99m-diethylenetiamine pentaacetic acid (DTPA) as an index of glomerular filtration rate and iodine-131-orthoiodohippurate (OIH) as an index of renal blood flow. Captopril (25 mg orally, crushed) was administered 1 hour before the second study. Renal artery stenosis was defined as a stenosis exceeding 70%. Renographic criteria were then established, retrospectively, to differentiate renal artery stenosis from essential hypertension based on (1) asymmetry of function and (2) the presence of captopril-induced changes. RESULTS: Renal artery stenosis was detected in 35 of 55 patients (21 with unilateral and 14 with bilateral stenosis). Three criteria were established for diagnosing renal artery stenosis: (1) a percent uptake of DTPA by the affected kidney of less than 40% of the combined bilateral uptake, (2) a delayed time to peak uptake of DTPA, which was more than 5 minutes longer in the affected kidney than in the contralateral kidney, (3) a delayed excretion of DTPA, with retention at 15 minutes, as a fraction of peak activity, more than 20% greater than in the contralateral kidney. The presence of one or more of these criteria was diagnostic of renal artery stenosis, with a sensitivity and specificity of 71% and 75%, respectively before captopril administration, and 94% and 95% after captopril administration. Lesser degrees of asymmetry (i.e., uptake of 40% to 50%) had very poor diagnostic specificity. Among patients with bilateral stenoses, asymmetry identified the more severely affected kidney, but the presence or absence of stenosis in the contralateral kidney could not be reliably determined. When pre- and post-captopril studies were compared, the presence of captopril-induced scintigraphic changes was a highly specific finding for renal artery stenosis, but occurred in only 51% of the cases. OIH scintigraphy provided similar results, with slightly lower sensitivity and specificity. CONCLUSION: Asymmetry of DTPA uptake, time to peak uptake, or retention seen on a single post-captopril renogram is a highly sensitive and specific finding in detecting renal artery stenosis but does not distinguish unilateral from bilateral disease. If renograms are obtained both before and after captopril administration, the presence of captopril-induced change is a highly specific finding for the detection of renal artery stenosis, but the sensitivity of this finding is low.

Antihypertensive Agents↗

Food preferences in families.

Preferences for a wide variety of foods were examined in families: 77 students, plus their siblings, mothers and fathers, for a total of 241 subjects. The food preferences of family members were more similar than would be expected by chance. However, this occurred entirely in the comparisons between spouses and between female family members. The results also indicated sex and age differences in family members' food preferences. For example, females tended to prefer low-calorie foods more when they were older, while males tended to prefer alcoholic beverages more when they were older. Both males and females showed a greater preference for coffee when they were older. Some of the variance in food preferences can be explained by an individual's family members' food preferences, as well as by the individual's sex and age.

Adolescent↗

Preoperative use of 3D volume rendering to demonstrate renal tumors and renal anatomy.

With increased use of computed tomography (CT) and abdominal ultrasonography, the indications for nephron-sparing surgery are also increasing. Triphasic helical CT and three-dimensional (3D) volume rendering can be combined into a single noninvasive test to delineate renal tumors and normal and complex renal anatomy prior to nephron-sparing surgery. This combination technique has proved accurate and very useful for both preoperative and intraoperative planning by demonstrating renal position, tumor location and depth of tumor extension into the kidney, relationship of the tumor to the collecting system, and renal vascular anatomy. Knowledge of the position of the kidney relative to the lower rib cage, iliac crest, and spine helps in planning the initial surgical incision. By depicting tumor location and depth of extension, helical CT with 3D volume rendering helps ensure complete tumor excision and conservation of adjacent normal renal parenchyma. Depiction of the relationship of the tumor to the collecting system helps anticipate further tumor extension and minimize postoperative complications. Identification of normal renal vasculature and anatomic variants can help minimize ischemic injury and intraoperative bleeding. Radiologists should be familiar with current indications for nephron-sparing surgery and understand what information is required prior to surgery.

Blood Loss, Surgical↗