Clinical and radiological findings in patients with gas forming renal abscess treated conservatively.

PURPOSE: Emphysematous pyelonephritis in diabetics is considered a potentially lethal infection. Mortality rates of patients treated conservatively approaches 80% in some series. These patients often present with signs of sepsis or septic shock. In contrast, gas forming renal abscess is rare, with patients presenting entirely differently from those with emphysematous pyelonephritis. To our knowledge this process has been previously described only in isolated case reports. We describe a series of 5 patients with this distinct process. MATERIALS AND METHODS: We reviewed the clinical and radiological features of 5 patients with gas forming renal abscesses. RESULTS: Each patient presented with diabetes mellitus with initial blood glucose ranging from 313 to 552 mg./dl., fever (average 101F), flank or abdominal pain and pyuria. No patient had evidence of septic shock at hospitalization. Escherichia coli was the documented organism in each case. Mild renal insufficiency was noted in most patients based on serum creatinine. Radiological evaluation revealed gas filled pockets within the renal parenchyma, which were most effectively shown by computerized tomography (CT) of the abdomen. There was no radiological evidence of pus. Percutaneous drainage of an abscess in 1 case did not produce any purulent material or alter the clinical course. Each patient responded to correction of the underlying metabolic abnormalities with intravenous antibiotics (average 23 days) followed by prolonged oral antibiotic therapy (average 9 weeks). In contrast to the management of emphysematous pyelonephritis, surgical or percutaneous drainage was not necessary. Serial CT revealed complete resolution of gas in the parenchyma within 6 months in patients with long-term followup. Of note, gas was persistent on CT months after infection had clinically resolved. CONCLUSIONS: We describe a unique entity within the spectrum of pyelonephritis. The clinical appearance of gas forming abscesses within the renal parenchyma without liquefaction in diabetic patients was remarkably benign compared to the radiographic appearance of the disease process. Conservative management with intravenous and oral antibiotics was successful in each patient, avoiding the need for invasive intervention.

Effect of montelukast on single-dose theophylline pharmacokinetics.

The effect of montelukast (MK-0476), a cysteinyl leukotriene receptor antagonist in development for treatment of asthma, on single-dose theophylline plasma concentrations was studied in three separate clinical trials. Montelukast was evaluated at 10 mg once daily (the clinical dosage), 200 mg once daily, and 600 mg (200 mg three times daily). At the clinical dosage, montelukast did not change single-dose theophylline plasma concentration in a clinically important manner. The geometric mean ratios for theophylline area under the plasma concentration versus time curve (AUC0-->infinity ) (0.92) and maximal plasma concentration (Cmax ) (1.04) were well within the predefined and generally accepted bioequivalence range of 0.80 and 1.25. Montelukast decreased theophylline Cmax by 12% and 10%, AUC0-->infinity by 43% and 44%, and elimination half-time by 44% and 39% at 200 mg/d (oral and intravenous, respectively), and at 600 mg/d, montelukast decreased theophylline Cmax by 25%, AUC0-->infinity by 66%, and elimination half-time by 63%. These results show that montelukast at the clinical dosage did not change theophylline pharmacokinetics in a clinically important manner, but at 20- to 60-fold higher dosages, montelukast significantly reduced the theophylline pharmacokinetics parameters; an apparent dosage dependence is suggested.

A study of the interaction between dirithromycin and astemizole in healthy adults.

The effect of a standard regimen of dirithromycin, a macrolide antibiotic, on the single-dose pharmacokinetics of the H (1) receptor blocker astemizole was evaluated in a sample of 18 healthy young adults (nine males and nine females). The study was conducted in a two-way cross-over fashion after the subjects had been randomly given either dirithromycin (two 250 mg tablets) or placebo (two tablets) every morning for 10 days. On the morning of the fourth dose of either dirithromycin or placebo each subject ingested a single 30-mg oral dose (three 10-mg tablets) of astemizole. The disposition kinetics of both astemizole and its major metabolite, N-desmethylastemizole, were characterized after measuring the concentrations of both analytes in the serum fraction of serial blood samples collected for 14 days after the astemizole dose. In addition, corrected QT (QT(c) ) intervals were estimated from electrocardiogram rhythm strips that were run 24 hours prior to the astemizole dose, 12 hours after the astemizole dose, and after the last treatment (dirithromycin or placebo) dose in both study periods. Pharmacokinetic parameters that were measured for both astemizole and N-desmethylastemizole during each treatment were: C(max), t(max), AUC (0-infinity), CL(oral), half-life, and volume of distribution (V). None of the parameters for N-desmethylastemizole was different when comparing data by ANOVA from the dirithromycin treatment period with that of the placebo treatment period. On the other hand, during dirithromycin treatment astemizole CL(oral) was 34% slower, volume of distribution was 24% larger, and half-life was 84% longer. Generally, all QT ( c ) intervals did not appear to be affected by dirithromycin treatment. The changes in astemizole kinetics could not be attributed to its N-demethylation since the dispositional kinetics of N-desmethylastemizole were unaffected by dirithromycin. Therefore, it is difficult to ascertain the clinical significance of the changes in astemizole kinetics. Since there were no significant differences for mean QT(c) intervals and no effect of dirithromycin treatment on N-desmethylastemizole kinetics, it is unlikely that a standard regimen of dirithromycin would place a patient taking astemizole at an increased risk of torsade de pointes or related ventricular arrhythmias.

Endoscopic management of upper tract urothelial tumors.

We evaluated renal-preserving endourology in the diagnosis and management of upper tract urothelial tumors. Referral patients were identified for the endourologic management of upper urinary tract tumors between January 1990 and May 1996 at two tertiary care referral centers. Chart reviews, indications for intervention, and treatment outcomes were assessed. Twenty patients (mean age 66 years; range 32-89; males 14; females 6) underwent endourologic diagnosis and/or management of upper tract urothelial neoplasms. Mean follow-up was 25 months. The diagnosis of transitional cell carcinoma (TCC) was endoscopically confirmed in all cases. Twenty-one biopsies were performed for pathological diagnoses; one identified pathological muscle that assisted in clinical staging. Percutaneous approaches were required in four patients (six kidneys) as a result of inadequate retrograde access or excessive tumor burden. Four (44%) renal pelvic tumors recurred after long-term follow-up; ureteral recurrences occurred in 4 (80%) of 5 patients. Open surgery was required in six patients for excessive tumor burden/concurrent muscle invasive bladder tumors. No endoscopically managed patient developed metastatic disease. No patient died as a result of TCC. Endourologic biopsies are small, yet sufficient for pathological diagnoses of upper tract tumors; most biopsies lack muscle to evaluate staging. Recurrent upper tract tumors are common and may require multiple staged endoscopic interventions. Successful endoscopic management of upper urinary tract neoplasms is primarily related to tumor burden and pathological grade. Minimally invasive endourologic management of upper tract tumors should be considered in select patients. Open surgical management does not equate with failure.

Controlled study of the putative interaction between famotidine and theophylline in patients with chronic obstructive pulmonary disease.

The effects of famotidine (80 mg per day), cimetidine (1600 mg per day), and placebo on theophylline pharmacokinetic parameters in chronic obstructive pulmonary disease (COPD) patients were compared. This was an open-label, randomized, three-period cross-over study, in which each subject first underwent a seven-day theophylline washout period, and thereafter received three single intravenous doses of theophylline (5 mg/kg infused over 30 minutes) during the study. Each of the experimental treatments was administered orally every 12 hours for a total of 9.5 days (19 doses). Theophylline was infused after the 17th dose of each treatment. Fourteen serial blood samples were collected before the start of each infusion, and for 30 hours after the end of each infusion. Plasma samples were assayed for theophylline, pharmacokinetic parameters were estimated, and treatment effects on each parameter were compared. Fourteen COPD patients completed all three periods of the investigation. Famotidine treatment had virtually no effect on any of theophylline's pharmacokinetic parameters. In contrast, cimetidine treatment significantly altered every pharmacokinetic parameter of theophylline as follows: Cimetidine decreased theophylline geometric mean CL from 2.74 L/h to 2.07 L/h (P < .001), and prolonged theophylline harmonic mean half-life from 6.6 to 9.6 hours (P < .001) and mean residence time from 10.8 to 15.0 hours (P < .001). Cimetidine treatment slightly increased theophylline volume of distribution by approximately 10%, and that change also was statistically significant (P = .032). The authors conclude that the treatment effects of cimetidine on theophylline pharmacokinetic parameters were in accord with those reported by others, and that famotidine treatment had no effect on any of theophylline's pharmacokinetic parameters in COPD patients.

Transrectal ultrasound in the evaluation of rhabdomyosarcoma involving the prostate.

OBJECTIVE: To evaluate transrectal ultrasound as a means of diagnosis and of monitoring patients with rhabdomyosarcoma involving the prostate. PATIENTS AND METHODS: Serial transrectal ultrasonography was utilized to evaluate prostatic rhabdomyosarcoma in three patients. RESULTS: Unlike prostatic adenocarcinoma and transitional cell carcinoma involving the prostate, which are predominantly hypoechoic, the echogenicity of rhabdomyosarcoma is similar to that of the normal prostate. Transrectal ultrasound provided a simple means of monitoring prostate size and sampling tissue in these patients. CONCLUSION: Transrectal ultrasound imaging can be useful in both diagnosis and evaluation of treatment response as well as provide easy access for biopsies in patients with rhabdomyosarcoma involving the prostate.

Short report: a comparative study of the interaction between antacid and H2-receptor antagonists.

The influence of concomitant antacid administration on the relative bioavailability of the H2-receptor antagonists cimetidine, famotidine, nizatidine and ranitidine, was investigated in a panel of 21 healthy, adult male volunteers in an eight-way crossover trial. Administration with antacid reduced the bioavailability of all agents tested. The reduction in area under the serum concentration-time curve (AUC) was greatest for cimetidine (23%) and ranitidine (26%) and least for nizatidine (12%) and famotidine (19%). Reductions in peak serum concentration (Cmax) followed a similar pattern. The times of peak serum concentrations were not affected by antacid. Comparison of the relative bioavailability among all drugs tested showed no statistically significant differences in the effect of antacid administration on these agents. However, a high degree of intersubject variability was observed.

Medical therapy alone for the treatment of gas forming intrarenal abscess.

Gas forming renal infections are severe, potentially lethal conditions. Gas formation in an intrarenal abscess is extremely rare. Formerly, these patients were uniformly treated by a combined medical and surgical approach. We describe 2 patients with intrarenal gas abscess who were successfully treated with antibiotics alone. We review the literature concerning intrarenal gas abscess and propose a pathophysiological mechanism for its formation as well as a treatment schema.

Transurethral ultrasound-guided laser-induced prostatectomy: National Human Cooperative Study results.

Between November 1990 and March 1992, 150 patients at 10 United States institutions were treated with transurethral ultrasound-guided laser-induced prostatectomy (TULIP) for the relief of bladder outlet obstruction secondary to benign prostatic hypertrophy. The TULIP system incorporates ultrasound visualization with a 90-degree angle, side-firing laser to effect coagulation necrosis of prostate tissue. The overall preoperative prostate volume in this TULIP study was 40 cc and all types of prostatic enlargement, including median lobe obstruction, were treated. There were no intraoperative complications, with no hemorrhage or post-transurethral resection syndrome, and no blood transfusions were required. Hospital stay averaged 1.7 days and 83% of the patients went home after a 1-night stay. We evaluated 63 patients at 6 months after the TULIP procedure. Mean symptom scores decreased from 18.8 to 6.1, for a 68% improvement. The mean peak flow increased from 6.7 ml. per second preoperatively to 11.9 ml. per second, for a 78% improvement. Overall, 87% of the patients exhibited at least 50% improvement in either the symptom score or peak flow parameter, while 49% of the patients demonstrated at least a 50% improvement in both parameters.

Absence of an inhibitory effect of omeprazole and nizatidine on phenytoin disposition, a marker of CYP2C activity.

The effects of omeprazole (40 mg orally per day) and nizatidine (300 mg orally per day) on the disposition of phenytoin (4.5 mg kg(-1) p.o. single dose) were studied in 18 healthy, young adult males. Total and unbound plasma concentrations of phenytoin were measured for 48 h after each dose of phenytoin. Neither treatment altered the disposition kinetics of phenytoin, the hydroxylation of which is mediated specifically by cytochromes P450 of the 2C subfamily.

Cisplatin, methotrexate and vinblastine plus surgical restaging for patients with advanced transitional cell carcinoma of the urothelium.

Chemotherapy with cisplatin, methotrexate and vinblastine (CMV) is active in advanced transitional cell carcinoma of the urothelium. Aggressive surgical resection of residual disease following responses produced by CMV was incorporated into a combined modality approach. Between 1982 and 1990, 64 patients were entered into the study. Of 55 patients evaluable for response 11 (20%) had a pathological complete response, 14 (25%) achieved a complete response following resection of residual disease and 5 (9%) whose disease was not surgically restaged had a clinical complete response. The overall complete response rate was 55%. Patients with liver, lung or bone involvement had significantly decreased survival compared to patients without visceral disease (p = 0.002). With a median followup exceeding 50 months, 14 patients (22% of all patients entered into the study) were free of disease at 23 to 98+ months. There were no deaths related to treatment. CMV produced high rates of response in patients with advanced disease, including those with distant metastases. Surgical resection of residual disease following responses produced by chemotherapy proved to be feasible, without treatment related mortality, and may have prolonged survival in selected cases.

Renal cell carcinoma.

The behavior of renal cell carcinoma remains one of the most unpredictable of the genitourinary neoplasms. Once this disease has spread beyond the confines of the kidney, it is extremely difficult to control. This year, emphasis has focused on the characteristic cytogenetic and chromosomal changes that are seen in this tumor that help to explain partially its enigmatic behavior. Immunotherapy remains the mainstay of nonsurgical therapy. Recent studies have examined the efficacy of using combinations of interferons, interleukin-2, or specific subpopulations of lymphoid cells to control metastatic renal cell carcinoma. The role of surgery in metastatic disease, tumor extending into the vena cava, and parenchyma-sparing operations continues to be examined. This review examines the most recent literature on each of these aspects in the treatment of this difficult and challenging tumor.

Distribution of lactoferrin in the normal and inflamed human prostate: an immunohistochemical study.

A polyclonal rabbit antibody to lactoferrin was used to localize the distribution of lactoferrin within the different zones of the normal human prostate as well as within the inflamed human prostate. Cases of normal central zone, peripheral zone, periurethral glandular tissue, as well as cases in which foci of moderate to severe inflammation, along with varying degrees of inflammation-related atrophy, were studied. In cases with inflammation, the staining pattern of lactoferrin was compared to the staining pattern of prostate-specific antigen. Within the central zone, lactoferrin staining occurred in numerous individual cells peppered throughout the epithelium as well as within multiple intraepithelial lumens (lacunae). These lacunae were often numerous enough to give the central zone epithelium a fenestrated appearance; they were not seen in any of the other regions of the prostate. With the exception of an occasional individual cell or isolated positive gland, normal peripheral zone exhibited very little lactoferrin activity. Staining within the transition zone was similar to that seen in the peripheral zone. Staining within the urethral lining of the epithelium in the periurethral glands showed a distinct pattern of frequent intense staining involving the entire gland; frequent individual positive cells were also often seen. Three patterns of staining were identified in prostatic inflammation. Mild periglandular chronic inflammation produced foci of epithelial lactoferrin positivity that coincided precisely with the areas of inflammation. Severe acute inflammation produced strong staining within luminal secretions while cytoplasmic staining was limited to the luminal surface of the epithelium. Post-inflammatory atrophy showed intense diffuse lactoferrin staining in the scant cytoplasm of the atrophic epithelium. In 12 of the 17 cases of inflammation that were studied, areas of post-inflammatory atrophy or severe inflammation commonly showed absence of prostate specific antigen staining and epithelium that was strongly lactoferrin-positive. Within the normal human prostate, lactoferrin appears to be produced primarily within the epithelium of the central zone, periurethral glands, and lining epithelium of the prostatic urethra. Lactoferrin-filled central zone lacunae appear to be structures unique to the central zone. The distribution of lactoferrin in the periurethral glands and urethral lining epithelium, along with the intense production of lactoferrin in the presence of inflammation, and the preservation of lactoferrin production in severe inflammation or atrophy suggest that lactoferrin may be a key component of the inflammatory response within the human prostate.

Transitional cell carcinoma of the prostate in patients undergoing radical cystoprostatectomy.

To assess the impact of prostatic involvement with transitional cell carcinoma we reviewed the clinical outcome of 49 patients with transitional cell carcinoma of the prostate. In addition, 115 step-sectioned cystoprostatectomy specimens removed for bladder transitional cell carcinoma were studied to determine the true incidence of secondary prostatic involvement by transitional cell carcinoma. Specimens from 300 prostates removed for prostatic adenocarcinoma also were reviewed to investigate the presence of incidental transitional cell carcinoma arising within the prostate. Transitional cell carcinoma was found in 29% of the step-sectioned specimens and in none of the radical prostatectomy specimens. The presence of prostatic invasion either into the stroma or involving prostatic ducts and acini only had no adverse effect on outcome. Lymph node status and bladder stage, and not prostatic invasion were the determining factors of survival. The presence of seminal vesicle involvement or prostatic stromal invasion appeared to predict for lymph node involvement. With a mean followup of more than 3 years 75% of our patients who had negative lymph nodes and low stage bladder lesions are alive without evidence of disease. In our series prostatic involvement by transitional cell carcinoma did not impact on survival when patients were treated aggressively with radical cystoprostatectomy.

Renal cell carcinoma.

Renal cell carcinoma represents a significant challenge to surgeons and oncologists treating urologic malignancies. Diagnostically, it is critically important to identify the precise extent of the tumor prior to therapeutic intervention. Therapeutically, a number of controversies continue to be debated, including the role of renal-conserving surgery and the role of surgery in patients with metastatic disease. New research is beginning to identify factors involved in the multidrug-resistant properties of these tumors that may allow us, in the future, to treat these tumors more effectively with systemic chemotherapy. Utilizing immunotherapy in the form of autolymphocytes, interferon, interleukin-2, or combinations of these regimens, a number of exciting advances have been made in the treatment of metastatic renal cell carcinoma. This review examines the most recent literature on each of the above-mentioned aspects in the treatment of this difficult and challenging tumor.

Post-translational modification of proteins by 15-carbon and 20-carbon isoprenoids in three mammalian cell lines.

A number of cellular proteins, including p21ras, lamin B, and the G-protein gamma subunits, undergo post-translational modification by 15-carbon farnesyl or 20-carbon geranylgeranyl isoprenoid moieties derived from pyrophosphate intermediates of the cholesterol biosynthetic pathway. In this study, isoprenylated proteins in three mammalian cell lines (Hela cells, Rat-6 fibroblasts and COS cells) were radiolabeled with an isoprenoid precursor, [3H]mevalonate, and resolved by SDS gel electrophoresis. Groups of proteins with different molecular masses were eluted from the gels and the chain-lengths of the radiolabeled isoprenyl groups, released from the proteins by Raney-nickel-catalyzed desulfurization, were established by gel permeation chromatography. 15-Carbon and 20-carbon isoprenyl groups were found in separate classes of proteins within each cell line. With the exception of p21ras, which incorporated a 15-carbon group when expressed in COS cells, the proteins in the region of the 21-28 kDa ras-related GTP binding proteins contained mostly 20-carbon isoprenyl chains. In contrast, proteins belonging to the 66-72 kDa nuclear lamin family, as well as unidentified proteins with molecular masses of 41-46 kDa and 53-55 kDa, contained predominantly 15-carbon isoprenyl chains. The chain-lengths of the isoprenoids associated with particular classes of proteins did not vary from one cell line to another, suggesting that the nature of the isoprenoid modification (farnesyl versus geranylgeranyl) is determined by intrinsic structural features of the proteins, rather than the cell type in which the proteins are expressed.

The effects of Rumalon, a glycosaminoglycan peptide complex, in a partial meniscectomy model of osteoarthritis in rabbits.

The effects of Rumalon, a glycosaminoglycan peptide complex (GP-C), were evaluated in a partial meniscectomy model of osteoarthritis (OA). When rabbits were treated with Rumalon, 0.25 ml/kg 3 times/week for 12 weeks after partial meniscectomy, the proportion of animals that developed cartilage ulceration was lower than that in untreated meniscectomized rabbits (p less than 0.05). At 6 weeks sacrifice, the same dose of Rumalon was associated with a trend toward reduction in the number of animals with ulcerations. Rumalon administered at a dose of 0.5 ml/kg for 12 weeks reduced the number of animals with ulcers, although not at the p less than 0.05 level of significance. Semiquantitative histologic evaluations revealed no differences between control and treatment groups either in the thickness of articular cartilage, density of cells present, safranin-O stain or ratio of DNA/protein. Increased proteoglycan synthesis characteristic of OA was modulated toward normal in association with Rumalon therapy. Diminished OA changes in response to Rumalon are consistent with an ameliorative response to this agent in the partial meniscectomy model in the rabbit.

Splenic abscess arising by direct extension from a perinephric abscess.

A case of a perinephric abscess invading the spleen in a 25-year-old woman with bladder exstrophy is reported. Treatment utilized both percutaneous drainage and open surgery. Perinephric abscesses have not been previously reported to extend into the spleen.