Effects of homoharringtonine on protein glycosylation in human bladder carcinoma cell T-24.

Rates of [3H]glucosamine and mannose incorporation into glycoproteins and dolichol-linked oligosaccharides in exponentially growing T-24 bladder cancer cells were examined after exposure to homoharringtonine (HHT). Two-h treatment of HHT (10 ng/ml) reduced [3H]glucosamine and mannose incorporation into the glycoproteins to 61% and 32% of controls. Concomitantly, respective sugar incorporation into dolichol-linked oligosaccharides was elevated 29% and 30% above control. The maximal inhibition of glycoprotein biosynthesis and stimulation of the lipid-linked oligosaccharides occurred within 2 to 4 h after exposure to 50 ng/ml of the drug. Prolonged drug exposure (greater than 8 h) resulted in generalized suppression of glycoprotein biosynthesis and lipid-linked oligosaccharide formation. The kinetic study indicated that the time course on reduction of glycoprotein biosynthesis and accumulation of dolichol-linked oligosaccharides paralleled the decline in protein synthesis. Further, the inhibition of glycoprotein synthesis and stimulation of dolichol-linked oligosaccharides were reversible 4 h after drug withdrawal. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of the [3H]mannose-labeled glycoprotein revealed no pronounced difference between HHT-treated and control cells. These data suggest that the inhibition of glycosylation results from combined decrease of acceptors for glycoprotein biosynthesis with a simultaneous accumulation of the dolichol-linked oligosaccharides. Collectively these data may account for many of the HHT-induced bioresponses.

The effects of oral pentoxifylline on interleukin-2 toxicity in patients with metastatic renal cell carcinoma.

Interleukin-2 (IL-2) mediates the regression of metastatic renal cell carcinoma, but clinical application has been limited by associated toxicities. Preclinical studies show that pentoxifylline (PTXF), a methylxanthine derivative, inhibits IL-2 toxicity while preserving anti-tumour efficacy. This study was designed to determine whether oral PTXF would alter IL-2-induced toxicities. Patients with disseminated renal cell carcinoma were treated with continuous infusion of 18 x 10(6) IU/m2/24 h for 4 days followed by 3 days without treatment, for 4 consecutive weeks. After a 2-week interval, the 4-week treatment cycle was repeated. All patients concomitantly received oral PTXF (2000 mg/24 h) in five divided doses. Despite the co-administration of PTXF, all patients demonstrated a spectrum and severity of toxicities consistent with previous reports of continuous infusion of IL-2 alone. There was considerably more nausea and vomiting associated with the administration of PTXF which improved on withdrawal of PTXF. Oral PTXF in IL-2 therapy did not show any substantiated benefit. Indeed, patients suffered more severe nausea and vomiting than if they had received IL-2 alone, resulting in the early termination of the trial.

Bilateral or unilateral ureteroneocystostomy for unilateral reflux.

Thirty-five cases of unilateral reflux treated by ipsilateral ureteroneocystostomy have been reviewed to determine the incidence of subsequent contralateral reflux. The low incidence (11 per cent) suggests that bilateral reimplant should not be performed routinely in patients undergoing surgery for unilateral reflux. Analysis of this group of patients failed to show any preoperative findings which would help to predict those in whom contralateral reflux is most likely to develop. Our study and the review of the literature suggest that those who demonstrate reflux in the contralateral ureter at any time prior to surgery are more likely to reflux subsequently; therefore, in this group of patients bilateral reimplantation is indicated.

Patient compliance in treatment of prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonist.

Luteinizing hormone-releasing hormone (LHRH) agonist therapy is commonly used as a form of hormonal ablative therapy in patients with advanced prostate cancer. It is important to administer LHRH agonist every four weeks. Any delay of more than two weeks is associated with the risk of disease flare. A retrospective review of two groups of patients were compared. Twenty-five patients treated at the Veterans Administration Medical Center, Louisville, Kentucky, showed that 44 percent missed one or more injections and 24 percent had a delay of more than two weeks after the scheduled time for another injection. Twenty-three patients were treated by a private practice group in Louisville, Kentucky. There were no problems with compliance. An office nurse kept a separate register for patients receiving LHRH agonist therapy and their appointments. For LHRH therapy to be effective, we believe that the level of compliance one could expect from an individual should be determined before instituting LHRH agonist therapy. If good compliance is not assured, alternative forms of hormone ablative therapy may be preferable for patients with advanced prostate cancer.

Diethylstilbestrol in treatment of postorchiectomy vasomotor symptoms and its relationship with serum follicle-stimulating hormone, luteinizing hormone, and testosterone.

Vasomotor symptoms such as hot flushes and profuse sweating have been described after bilateral orchiectomy. We evaluated 26 patients who had undergone bilateral orchiectomy for prostatic carcinoma to determine the incidence of vasomotor symptoms and the efficacy of low-dose diethylstilbestrol (DES) in the treatment of those symptoms. Measurements of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were performed to look for endocrine patterns which may be related to the presence of vasomotor symptoms. Fourteen patients (54%) reported the presence of vasomotor symptoms beginning one to four weeks after surgery. These patients were treated with DES or placebo in a double-blind crossover trial. The frequency and severity of hot flushes were significantly reduced during the time DES was given. This was accomplished with a low dose of 1 mg daily of DES which avoids the cardiovascular complications of higher doses. We found no correlation between the presence, severity, or frequency of hot flushes and serum gonadotropin or testosterone concentrations.

Infundibulopelvic dysgenesis: a spectrum of obstructive renal disease.

Infundibulopelvic dysgenesis is an obstructive process of the pyelocalyceal system that is responsible for a spectrum of congenital renal disorders. The site and degree of narrowing in the infundibulopelvic system produce the various congenital anomalies like hydrocalycosis, calyceal diverticula, ureteropelvic junction stenosis, and multicystic kidney. A classification with illustrative cases is presented showing a common pathogenesis of these congenital obstructive anomalies.

Extracorporeal shock-wave lithotripsy in transplanted kidney.

Urolithiasis is the least described urologic sequela of renal transplantation. We describe a renal transplant patient who presented with painless gross hematuria. An intravenous pyelogram demonstrated a 4 x 7-mm calculi in the region of the ureteropelvic junction, causing moderate hydronephrosis. The patient was treated successfully with extracorporeal shock-wave lithotripsy (ESWL). Serum creatinine and twenty-four-hour creatinine clearance were unchanged from levels prior to ESWL.

Priapism associated with asplenic state.

Priapism may be primary (idiopathic) or secondary to sickle cell anemia, trauma, leukemia, drugs, venous thromboembolic diseases, and other less common disorders. This study concerns 21 patients with priapism treated during a period of ten years. Nine patients (43%) had sickle cell anemia. Of the 12 individuals (57%) classified as idiopathic, 3 (25%) had previously undergone surgical splenectomy for benign conditions. Considering the propensity for this unusual condition to develop in patients with hemoglobinopathy-induced hyposplenism, the possibility of a relationship between the asplenic state and priapism is considered.

The influence of photodynamic therapy on the ultrastructure of the normal rat bladder.

Reduced bladder capacity is a major side effect for patients receiving photodynamic therapy (PDT) for bladder cancer. A rat bladder model has been developed to address both the vascular and tissue effects of the photodynamic treatment of the urinary bladder. Bladders were exteriorized and positioned in a plexiglass tissue bath. Effects on microvasculature were assessed during PDT of the bladder by recording luminal diameter changes in arterioles and venules. Animals receiving Photofrin II (10 mg kg-1) 30 min prior to PDT scored a statistically significant reduction in the diameter of the red blood cell column in the vessels, whereas administration of Photofrin II 48 h prior to PDT was ineffective. Morphological changes included significant endothelial and vascular myocyte damage in the 30 min PDT group alone. Among the other tissue components, the mucosal lining was minimally affected and the response of the muscularis was highly variable. Smooth muscle cell changes ranged from mild contraction to frank necrosis with many of the affected cells located near the altered vascular beds. These data suggest that the clinical symptoms of reduced bladder capacity can be accounted for by vascular damage and myocyte sensitivity. Further refinements in the Photofrin II and light doses used in therapy may reduce bladder complications and allow for better management of bladder cancer.

Cytohistologic correlation of urothelial lesions secondary to photodynamic therapy.

Qualitative cytologic evaluations of urinary bladder washings were performed on a selected population following photodynamic therapy for recurrent transitional cell carcinoma of the bladder. The seven patients were monitored trimonthly by cystoscopy, multiple biopsies and cytopreparations. Cancers reappeared in two of the five patients who initially responded to therapy. In the remaining two patients, the recurrent neoplasms were therapeutically refractory. Cytology detected recurrent cancer prior to biopsy confirmation and/or cytoscopic identification. Exfoliative cytology was correlated with the histopathology of the concurrent biopsies; a possible source for a false-positive cytodiagnosis was the cellular atypia of reepithelialized bladder mucosa. Dysplasia was not identified cytologically or histologically.

Transitional cell carcinoma of the anterior urethra.

We report a case of transitional cell carcinoma of the anterior male urethra. Unlike squamous cell carcinoma of the anterior urethra, which usually requires partial penectomy, transitional cell carcinoma of this location can be managed with conservative local resection and preservation of the penis. Possible explanations for the origin of this lesion are discussed.

Urethral strictures secondary to pelvic injury in children.

Surgical repair of a membranous urethral stricture is difficult because of the location and potential risks of incontinence, impotence and infertility. The treatment of 2 such strictures by the Badenoch pull-through urethroplasty is presented. The technique is described and its apparent advantages over other methods of repair are discussed.

Systemic influence of intravesical chemotherapy with verapamil.

The influence of the calcium blocker verapamil (VR) on systemic toxicity resulting from the intravesical instillation of Adriamycin (ADM) and thiotepa (THT) was assessed in mice. Eighty per cent of the animals receiving THT + VR developed a generalized alopecia. Data gathered at necroscopy failed to reveal any trauma to the major organs or the presence of a drug-induced myelosuppression. Combination of ADM and VR did not produce an enhancement of systemic toxicity, manifest as myelosuppression. The drug combination did not produce a cardiomyopathy as assessed by histologic examination. The use of VR in combination with antineoplastic agents posed no more of a threat to the animals than did the use of cytotoxin alone.