Posttraumatic renovascular hypertension after occult renal injury.

OBJECTIVE: Hypertension secondary to renal injury is an unusual problem, but one that occurs with some frequency in an active trauma unit. The incidence and management of posttraumatic renovascular hypertension at our Level I trauma center was reviewed. METHODS: A retrospective review of a trauma database was performed on patients treated by our trauma service between 1977 and 1996. Seven patients were identified who developed arterial hypertension as a direct result of a renal injury. RESULTS: All of the patients sustained multiple injuries, with five requiring celiotomy to control bleeding. Renal injuries were occult, and there was no compelling reason to suspect injury to the kidney. No patient had a history of hypertension or elevated arterial pressure on admission; however, sustained arterial hypertension was noted within 2 weeks to 8 months of injury. Arteriography was positive in all seven patients, with findings that included lacerations of the main renal artery, its major branches, or intrarenal constriction of the renal artery (presumably from scarring). Renal-vein renin assays localized to the injured kidney in six patients. Treatment included nephrectomy in four cases, revascularization in one case, and medical management in two cases. All of the patients treated operatively had prompt relief of their hypertension. The two patients treated soley by medical therapy had prompt, durable control of their arterial pressure with a single medication. However, medical treatment had failed before operation in several of the patients. CONCLUSIONS: Because of the serious complications associated with undiagnosed hypertension, new-onset or sustained hypertension after major trauma should be evaluated with attention to a possible renal cause.

Are learning objectives useful in evaluating medical school course and instructor performance?

We tested the hypothesis that learning objectives could be used to evaluate course and instructor effectiveness. Ninety-seven third-year medical students who had their surgical clerkship or their medical clerkship as their first clinical rotation were compared. The surgery clerks received 171 urologic learning objectives. Students taking the surgical clerkship had significantly higher postclerkship recognition of the learning objectives than did medical clerkship students. One year later, these students were again surveyed to determine whether they still knew the correct response to the learning objective. The follow-up survey showed that 50% of the students recognized objectives covered in five of the eight urology lectures, while the other lectures were not effective. Students who recognized the objective on the postclerkship evaluation were more likely to think the objective had been taught on this follow-up survey. These data suggest that learning objectives are useful for evaluating course and instructor effectiveness.

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.

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.

Retroperitoneal tumors with vena caval extension: a multidisciplinary approach.

In cases of retroperitoneal tumor with extension to the inferior vena cava (IVC), complete resection improves survival, but may require cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA). Since 1985, eight patients at our institution have had complete resection of retroperitoneal tumors with IVC or right atrial involvement. Preoperative evaluation included intravenous pyelography, computed tomography of the chest and abdomen, renal arteriography, and venography or magnetic resonance imaging of the IVC. Operative technique was determined primarily by the extent of IVC or RA involvement and included combined median sternotomy and laparotomy, control of the intrapericardial IVC, and radical tumor resection. IVC tumor thrombectomy was done using either temporary vascular occlusion, CPB, or CPB with HCA. Complete resection for improved survival of retroperitoneal tumors with IVC extension is technically feasible with acceptable morbidity and mortality rates. A multidisciplinary approach allows optimal management of these extensive tumors.

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.

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.

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.

Treatment of radiation or cyclophosphamide induced hemorrhagic cystitis using conjugated estrogen.

Five patients with severe hemorrhagic cystitis induced by radiation and/or cyclophosphamide were systematically treated with conjugated estrogen. Two patients received conjugated estrogen twice each day (1 mg. per kg.) intravenously, followed on day 3 and thereafter by 5 mg. per day orally. Hematuria decreased markedly 6 to 8 hours after the initial dose and urine color became light yellow within 1 to 3 days. The other 3 patients received 5 mg. conjugated estrogen per day orally and urine color became clear within 4 to 7 days. Hematuria did not recur during 12 to 22 months in 4 patients who received daily conjugated estrogen (1.25 mg.). However, transient episodes of mild hematuria persisted in 1 patient during the 3-month followup despite a higher dose of conjugated estrogen (10 mg. per day). Complications, including thromboembolism and other side effects associated with conjugated estrogen, were not observed in these patients. We postulate that conjugated estrogen controls hematuria in hemorrhagic cystitis by decreasing the fragility of the mucosal microvasculature of the bladder.

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.

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.

The response of the rat urinary bladder microcirculation to photodynamic therapy.

Light activation of dihematoporphyrin ether (photofrin II) has been used in the treatment of bladder tumors, yet the effects of this treatment on the normal urinary bladder microcirculation have not been determined. This study involved the use of in vivo television microscopy to observe the effects of light activation (530 to 560 nm., 175 mW/cm.) on the urinary bladder microcirculation of female Sprague-Dawley rats. Animals pretreated with dihematoporphyrin ether 30 minutes prior to light activation had high serum and low tissue concentrations of the photosensitizer and activation resulted in a statistically significant reduction of red blood cell column diameter in both arterioles and venules. The reduction was primarily due to mural thrombus formation with the occlusion remaining 60 minutes after activation. Animals pretreated 48 hours before activation had low serum and high tissue concentrations of dihematoporphyrin ether and activation had no microcirculatory effects apart from occasional platelet aggregation. These results suggest that the photodynamic effect on normal (non-neoplastic) tissue treated more than 48 hours after administration of dihematoporphyrin ether is probably due to a direct effect of light and the sensitizer on the smooth muscle of the bladder rather than an effect on the microcirculation.

Complications of whole bladder dihematoporphyrin ether photodynamic therapy.

Photodynamic therapy with dihematoporphyrin ether was used to treat superficial bladder tumors in 7 patients with a followup of at least 1 year. Each patient received treatment to the whole bladder and those with papillary lesions received additional focal treatment. At 3 months 4 of the 5 patients with papillary tumors (stages Ta and T1) and 1 of the 2 with diffuse carcinoma in situ (Tis) were free of disease. However, at 1 year only 3 patients remained free of disease. Of 5 patients with an increase in irritative bladder symptoms 4 had a contracted bladder, hydroureteronephrosis and vesicoureteral reflux. Deep bladder biopsies showed replacement of smooth muscle by fibrous tissue. Six patients had mild to moderate skin phototoxicity. We conclude that although photodynamic therapy is an attractive and exciting method to treat cancer, its use with dihematoporphyrin ether in cases of bladder carcinoma can be associated with significant complications. The correct treatment parameters for safe, effective therapy are not known to date.

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.