Expression and function of the leucine zipper protein Par-4 in apoptosis.

The prostate apoptosis response-4 (par-4) gene was identified by differential screening for genes that are upregulated when prostate cancer cells are induced to undergo apoptosis. The par-4 gene is induced by apoptotic signals but not by growth-arresting, necrotic, or growth-stimulatory signals. The deduced amino acid sequence of par-4 predicts a protein with a leucine zipper domain at its carboxy terminus. We have recently shown that the Par-4 protein binds, via its leucine zipper domain, to the zinc finger domain of Wilms' tumor protein WT1 (R. W. Johnstone et al., Mol. Cell. Biol. 16:6945-6956, 1996). In experiments aimed at determining the functional role of par-4 in apoptosis, an antisense par-4 oligomer abrogated par-4 expression and activator-driven apoptosis in rat prostate cancer cell line AT-3, suggesting that par-4 is required for apoptosis in these cells. Consistent with a functional role for par-4 in apoptosis, ectopic overexpression of par-4 in prostate cancer cell line PC-3 and melanoma cell line A375-C6 conferred supersensitivity to apoptotic stimuli. Transfection studies with deletion mutants of Par-4 revealed that full-length Par-4, but not mutants that lacked the leucine zipper domain of Par-4, conferred enhanced sensitivity to apoptotic stimuli. Most importantly, ectopic coexpression of the leucine zipper domain of Par-4 inhibited the ability of Par-4 to enhance apoptosis. Finally, ectopic expression of WT1 attenuated apoptosis, and coexpression of Par-4 but not a leucine zipperless mutant of Par-4 rescued the cells from the antiapoptotic effect of WT1. These findings suggest that the leucine zipper domain is required for the Par-4 protein to function in apoptosis.

Prospective DR matching for first cadaver donor renal allografts and retransplantation.

From January 1981 through 1983 80 cadaver donor renal allografts were transplanted at a single center utilizing prospective HLA-DR matching. All patients received at least two blood transfusions prior to transplantation. One year actual allograft survival of 77% for initial grafts and 57% for retransplantation was observed. When there was no DR mismatch the results were 84% and 80% respectively. Only 6% of no-DR-mismatch initial grafts were lost to rejection or patient death. These significantly better results were associated with decreased incidence of acute rejection episodes with transplants well matched for DR. Matching for A and B locus antigens conveyed no benefits in this series. Use of prospective DR matching for donor/recipient selection also resulted in efficient transplantation. Patients receiving initial grafts waited an average of 3.9 months while retransplanted patients waited an average of 13.5 months after being entered on the waiting list. The data suggest that if all transplant centers would preferentially share kidneys regionally on the basis of DR matching, nearly all patients could receive timely allografts with no DR mismatch and good results at one year with conventional immunosuppressive therapy.

Cushing's syndrome associated with a pheochromocytoma.

A norepinephrine producing right adrenal pheochromocytoma was associated with bilateral adrenal hyperplasia and clinically and biochemically evident Cushing's syndrome. Ectopic adrenocorticotropin production was suspected, but the six criteria for proof of ectopic adrenocorticotropin production could not be demonstrated. The diagnosis of Cushing's syndrome from ectopic hormone production by a pheochromocytoma requires a high index of suspicion and extensive biochemical and radiographic testing to confirm Cushing's syndrome, identify the cause of Cushing's syndrome, and localize the pheochromocytoma.

Cecoappendicovesicostomy: conduit-lengthening technique for use in continent urinary reconstruction.

OBJECTIVES: To describe a conduit-lengthening technique for use in continent cutaneous appendicovesicostomy (Mitrofanoff procedure). METHODS: Fifteen consecutive patients (4 male, 11 female) with a mean age of 14.2 years underwent tubularized cecal augmentation as a means to lengthen the catheterizable conduit while performing continent cutaneous appendicovesicostomy. RESULTS: All patients successfully underwent appendiceal lengthening by tubularizing the cecum, thus creating a continent cutaneous cecoappendicovesicostomy. With a mean follow-up of 18.7 months, all patients have a working catheterizable conduit. One case of stomal stenosis occurred, producing a 6.7% conduit-related complication rate. CONCLUSIONS: Cecoappendicovesicostomy is a safe and useful means of conduit lengthening for patients undergoing continent cutaneous appendicovesicostomy (Mitrofanoff procedure).

Comparison of serum and prostatic levels of tobramycin.

Tobramycin sulfate, an aminoglycoside antibiotic, has been shown to be effective in the treatment of complicated urinary tract infections. Because of this, a study was undertaken to determine the penetrance of tobramycin into the prostate gland. It was found that the drug is concentrated at inhibitory levels in the prostate gland after the routinely recommended administration and should be useful in the treatment of bacterial prostatic infection.

The utility of video-assisted thoracic surgery in the diagnosis of pulmonary metastases from renal cell carcinoma.

The definitive diagnosis of pulmonary metastases requires histologic confirmation. Traditional methods of obtaining tissue for histologic review include transbronchial approaches, percutaneous transthoracic needle biopsy, and open lung biopsy. The purpose of this study is to identify the most effective methods of obtaining histologic confirmation of pulmonary metastases. The utility of video-assisted thoracic surgery in diagnosing pulmonary metastases is demonstrated in 2 patients with metastatic renal cell carcinoma. The diagnostic yields and complication rates of transbronchial approaches, percutaneous needle biopsy, open lung biopsy, and video-assisted thoracic surgery are compared. Finally, an algorithm for the evaluation of pulmonary lesions is presented.

Evaluation of closed suprapubic cystostomy.

Closed suprapubic cystostomy is an expeditious procedure for a variety of clinical conditions requiring urinary drainage. Its benignity is reflected by a low complication rate of 1.6 per cent and no deaths in this series of 244 consecutive patients. Nevertheless, major complications can occur if proper technique is not adhered to or contraindications are not observed.

Leiomyosarcoma of renal vein.

Primary leiomyosarcoma of the renal vein has not been previously reported in the urologic literature. A case report with long-term survival is described and the literature reviewed.

Cloacal exstrophy.

Although each patient with cloacal exstrophy must be considered as a unique individual and much controversy still remains about the treatment of this complex syndrome, our review of the literature suggests that the previously detailed series of stages in the approach to this patient represents a conservative, individualized, yet successful approach.

"Stand-up" urologic endoscopy.

OBJECTIVES: To report the advantages of performing diagnostic and therapeutic urologic endoscopic procedures with the urologic surgeon in the standing-up position. METHODS: Our 25-year institutional experience with more than 10,000 cases of transurethral ablation of the prostate and other urologic endoscopic procedures, performed by the urologist in the standing-up position, was examined. A questionnaire of all 55 of our former urology residents was carried out to determine current practice trends. RESULTS: We have noted no drawbacks from performing transurethral surgery in the standing-up position. Ninety-two percent of the respondents believe that the standing-up position was more comfortable for endoscopic surgery than the sitting-down position. CONCLUSIONS: the standing-up technique of transurethral surgery minimizes positional stresses on the urologist's cervical and thoracic spine while optimizing endoscopic visualization and maneuverability. We recommend it in preference to the conventional sitting-down technique.

Cefazolin and cephalexin levels in prostatic tissue and sera.

A study was carried out on 18 patients given cefazolin intramuscularly and 17 patients given cephalexin by mouth preoperatively prior to transurethral resection of the prostate. Prostatic tissue and serum levels of the two drugs were determined and contrasted with previously reported mean inhibitory concentrations. It was found that cefazolin was present in the sera and prostatic tissues in levels greater than was cephalexin and that cefazolin frequently exceeded the minimum inhibitory concentrations necessary for sensitive organisms to be affected, whereas cephalexin did not. Therefore, it would appear that cefazolin would be preferable to cephalexin in treatment of acute bacterial prostatitis.

Renal vein thrombosis presenting as renal mass.

The excretory urogram of patients with acute renal vein thrombosis typically demonstrates symmetric enlargement of the involved kidney. We report a case of renal vein thrombosis that presented as a discrete renal mass on excretory urography and abdominal computerized tomography. The entity of renal vein thrombosis is briefly reviewed along with the computerized tomography findings seen in this setting.

Familial paraganglioma.

Extra-adrenal pheochromocytomas and paragangliomas are rare tumors of neural crest origin, most commonly found in the retroperitoneum. Because these tumors are so uncommon, relatively little is known about their natural history. Comparisons between adrenal pheochromocytomas and extra-adrenal pheochromocytomas have appeared in the medical literature. Like pheochromocytomas, paragangliomas may occur as functional or nonfunctional tumors. Furthermore, although the hereditary occurrence of pheochromocytomas is well documented, the familial nature of paragangliomas is unclear. We present the first report of a mother and son with nonfunctional paragangliomas occurring in the same anatomic location and describe their care and treatment.

Comparison of epsilon aminocaproic acid and normal saline for postoperative bladder irrigation following transurethral resection of prostate.

A prospective, randomized, double-blind trial of bladder irrigation with a 0.5% solution of epsilon aminocaproic acid (EACA) versus normal saline plus placebo was undertaken in 75 patients undergoing transurethral resection of the prostate for benign or malignant disease. Systemic absorption after irrigation with EACA was not detectable. No significant advantage, however, was demonstrated for the EACA solution over normal saline irrigation in measured postoperative blood loss, irrigant volume, hours of catheterization, or length of hospital stay.

Complications associated with preoperative radiation therapy and Iodine-125 brachytherapy for localized prostatic carcinoma.

Twenty-five consecutive patients with localized adenocarcinoma of the prostate treated with 1,050 rad preoperative radiation therapy and Iodine-125 seed brachytherapy arreviewed. Significant long-term postoperative complications included radiation cystitis (12%), radiation proctitis (4%), genital and leg edema (12%), stress incontinence (8%), total incontinence (4%), and impotence (26%). Complications occurred in 75 per cent of patients who received additional postoperative radiation. Improved staging with CT scan, lymphangiography, and Chiba needle biopsy of any possibly abnormal lymph nodes provided excellent preoperative staging with only 1 patient (6%) upstaged at surgery to Stage D1.

Nutritional assessment and therapy in advanced urothelial cancer.

Patients with advanced urothelial cancers often have cachexia and anorexia resulting in severe malnutrition and depressed immunologic function. Careful nutritional assessment early in their evaluation and early use of parenteral and enteral nutritional supplements play an important role in allowing these patients to withstand their therapies safely as well as in improving their prognosis.

'Hyperacute rejection' due to perfusion injury.

Two kidneys were harvested from a cadaver donor and subjected to pulsatile perfusion in an identical fashion with a perfusate which was free of cytotoxic antibody. Classical 'hyperacute rejection' occurred in the right kidney when transplanted into a male patient with no previous blood transfusion or transplants, and repeatedly negative tests for cytotoxic antibody. The left kidney was not transplanted and was examined by light, electron, and immunofluorescence microscopy as was the immediately removed, transplanted kidney. Despite the absence of any immunological pathogenetic mechanism in the non-transplanted kidney, virtually identical changes of 'hyperacute rejection' were seen in both kidneys. Thus,even technically satisfactory perfusion may cause a syndrome of 'hyperacute graft failure' secondary to non-immunologically mediated perfusion injury.

Does vesicoureteric reflux result in renal allograft failure?

Vesicoureteric reflux (VUR) into transplanted kidneys has been cited as an often disregarded but frequent complication of transplantation which is associated with a glomerular lesion that resembles membranoproliferative glomerulonephritis, marked proteinuria, and graft failure. To determine the prevalence of this complication in our transplant population, all of our 23 patients with marked proteinuria and 27 controls without proteinuria had voiding cystourethrograms performed approximately two years after transplantation. In our population, VUR was infrequent (8%). Moreover, in the three of the four cases detected renal function has not deteriorated and three of the four do not have marked proteinuria. We cannot confirm the suggestion that VUR is a frequent cause of late renal allograft failure.

Prevalence of hypertension in a renal transplant population on alternate-day steroid therapy.

A study of the prevalence of hypertension in a group of renal transplant patients on alternate-day maintenance steroid therapy was conducted. Twenty-four percent of the transplant clinic population was hypertensive. The factors that were associated with a lower prevalence of hypertension were good graft function, bilateral nephrectomy of the patients' own diseased kidneys (although the majority of our patients without bilateral nephrectomy are normotensive), and use of a living related donor. We conclude that the prevalance of hypertension in transplant patients on alternate-day steroid therapy is low. In the presence of all these favorable factors, only 6% of allograft recipients were hypertensive.

Laparoscopic live-donor nephrectomy.

Laparoscopic nephrectomy with ablative intent has been performed clinically. The current study aimed to determine whether a physiologically and anatomically intact kidney suitable for transplantation could be harvested laparoscopically. Three weeks after an ablative laparoscopic right nephrectomy, 15 pigs were divided into two groups: the study group (n = 10) underwent a laparoscopic live-donor left nephrectomy of the solitary kidney and conventional autotransplantation; the control group (n = 5) underwent an open live-donor left nephrectomy of the solitary kidney and conventional autotransplantation. All study kidneys underwent laparoscopic in situ hypothermic perfusion. The mean length of the left renal artery and vein were similar in the study and control groups: 3.1 cm and 3.4 cm, respectively, in the study group compared with 2.5 cm and 3.8 cm, respectively, in the control group (P = 0.5). No intraoperative renal vascular injuries or postoperative ureteral complications were noted in either group. Renal histopathologic examination immediately after live-donor nephrectomy and at 1 month post-transplant showed similar findings in the two groups. The mean serum creatinine at 7 and 30 days postoperatively was not significantly different: 2.1 mg/dL and 1.6 mg/dL, respectively, in the study group and 1.7 mg/dL, and 1.4 mg/dL, respectively, in the control group (P = 0.4). We conclude that laparoscopic live-donor nephrectomy can be performed safely and reproducibly in the porcine model.