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Purpose: The impact of onabotulinum toxin type A (BoNT-A) on bladder afferent nerve pathways and chemosensory functions is an active area of investigation. There may be a role for BoNT-A in disorders of the ureter; however, no histologic studies have assessed the effects of BoNT-A on ureteral tissue. Our objective was to develop an animal model of ureteral inflammation and determine the impact of ureteral BoNT-A instillation on known mechanisms of inflammation., Methods: The safety and feasibility of a novel animal model of ureteral inflammation was assessed. Through open cystotomy, the effect of ureteral BoNT-A instillation on inflammation was determined through H&E, masson's trichrome, Ki-67 stain, and prostaglandin E (PGE) synthase expression, a known marker of pain and inflammation in ureteral tissue. Urothelial microstructure was assessed using electron microscopy and standard histologic techniques., Results: All experiments were carried to completion, and no systemic signs of botulinum toxicity were seen. BoNT-A exposure was associated with a decrease in PGE synthase expression in a dose-dependent fashion. BoNT-A exposure was not found to impact collagen deposition or cell proliferation. Disruption of tight junctions between urothelial cells was observed under conditions of inflammation., Conclusion: We describe the feasibility of a novel in vivo model of ureteral inflammation and report the first histologic study of the effects of BoNT-A on the ureter. Preliminary findings show that BoNT-A attenuates ureteral PGE synthase expression under conditions of inflammation. The application of BoNT-A may provide anti-inflammatory and analgesic effects in the context of ureteral disorders.

Ketamine-associated cystitis is a well-recognised syndrome; yet upper urinary tract involvement remains poorly understood. We present the case of a 33-year-old man who developed ketamine-associated cystitis and ureteritis. The patient's severe bladder symptoms required subtotal cystectomy and orthotopic reconstruction. However, the associated ureteritis led to bilateral ureteric obstruction and renal failure. Bilateral autotransplantation with pyelovesicostomy was performed. This first case of autotransplantation for ketamine uropathy helps to demonstrate the potentially devastating effects of ketamine on the urinary tract., (2015 BMJ Publishing Group Ltd.)

Very rarely, dissemination of intravesical bacille Calmette-Guérin for superficial bladder cancer treatment can lead to a complication in the upper urinary tract. Two mechanisms for dissemination have been proposed: vesicoureteral reflux and hematogenous spread. We report a case of "BCGosis" with the clinical appearance of multifocal renal masses in a patient without ipsilateral reflux. This case highlights the importance of obtaining a renal biopsy in all patients previously treated with bacille Calmette-Guérin presenting with a renal mass. Furthermore, the findings from the present case suggest that vesicoureteral reflux might not be the only mechanism responsible for dissemination of bacille Calmette-Guérin to the upper urinary tract.

Bleeding of the ureteral wall during an anticoagulant treatment is a rare complication. We report the case of a 57-year-old white woman presented with macroscopic haematuria and lumbar pain with an overdose of anticoagulant treatment. Computed tomographic scan revealed the bleeding of the ureteral wall. Clinical improvement was excellent after correction of the haemostasis disorder.

The effects of alpha-naphthoflavone, an aryl hydrocarbon receptor (AhR) antagonist, on the reproductive toxicity and teratogenicity induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were investigated. Pregnant C57BL/6J mice were orally administered alpha-naphthoflavone either once on gestational day 12 (GD12; 50 microg/kg) or for 6 days (GD8-GD13; 5 mg/kg/day) followed by an oral challenge with TCDD (14 microg/kg) on GD12. Cesarean section was performed on GD18 for the evaluation of maternal and fetal toxicities. TCDD caused severe fetal malformations including cleft palate (43.7%) and renal pelvic and ureteric dilatations (100%). The administration of alpha-naphthoflavone either in a single treatment or 6-days remarkably reduced the incidence of cleft palate to 27.6% and 26.5%, respectively. In addition, the degree of renal pelvic and ureteric dilatations caused by TCDD were significantly attenuated by repeated treatment of alpha-naphthoflavone. These results suggest that AhR antagonists such as alpha-naphthoflavone could be promising candidates for reducing the incidence and severity of fetal malformations caused by TCDD exposure in utero.

Bovine glutaraldehyde cross-linked collagen is an injectable bulking agent used to treat urinary incontinence and vesicoureteral reflux. A 16-year-old girl had previously undergone left subureteral injection of collagen at the age of 6 years. She presented to our clinic after passing a 7-mm calcification with a history of hematuria and intermittent back pain. Computed tomography showed two hyperdense foci measuring 2 mm each in the region of the left ureterovesical junction that did not change on follow-up imaging. On cystoscopy, two submucosal calcifications were located medially and inferiorly to the left ureteral orifice and were removed endoscopically.

Intraluminal ureteral hematoma is a rare disease and only a few cases have been previously described. We report a case of intraluminal ureteral hematoma induced by anticoagulant therapy. A 65-year old man having the oral anticoagulant therapy for prevention of secondary thrombolism following atrial fibrillation was referred to us for gross hematuria. Ultrasound sonography (US) revealed right renal mild wide pelvis. Computed tomography (CT) showed the right ureteral submucosal hematoma. This ureteral hematoma penetrated the ureteral mucosa and caused macrohematuria. The patient had been anticoagulated on Warfarin with Bucolome for 18 days, so the prothrombin times (PT) was found to be excessively prolonged beyond the normal therapeutic range. The oral anticoagulation was stopped and intravenous Vitamin K2 was given, so PT was normalized. Though estimate hemorrhage quantity reached 1,200 ml, we had no blood transfusion. The hematoma was completely diminished 4 months later, no reccurence has been occurred. Bucolome has especially pharmacokinetic positive interaction to Warfarin, so we must check PT-INR frequently.

Congenital obstructive uropathy is associated with significant morbidity and mortality in the human neonate. The pathophysiology of congenital obstructive uropathy is poorly understood. There are very few experimental models of prenatal obstruction of the urinary tract, except in the fetal lamb or inbred rats. Prenatal exposure to Adriamycin in a rat model leads to a spectrum of malformations including urinary tract anomalies. We hypothesized that Adriamycin administration during a particular time frame could yield a high incidence of urinary tract anomalies and therefore designed this study to investigate the rates of urinary tract anomalies at different windows of Adriamycin injection in rat embryos. Adriamycin (1.75 mg/kg) was administered intraperitoneally to pregnant rats at different times from days 6 to 10 of gestation. Control animals were given saline. Embryos recovered on gestational day 21 by cesarean section were examined for urinary tract anomalies, and malformations were noted. Sections were then processed for paraffin embedding, sectioned at 5 mum, and stained with hematoxylin and eosin for histological examination. Anomalies of the urinary tract occurred maximally following Adriamycin administration on days 7, 8, and 9 of gestation (91.6%) compared with 16% of controls. The most common urinary tract anomaly in the Adriamycin group was bilateral megaureters with a hypoplastic bladder (81%). Other anomalies included unilateral or bilateral ureterohydronephrosis with a normal-sized bladder, duplex kidney, and unilateral or bilateral renal agenesis. In conclusion, the critical embryologic window for the development of bilateral megaureters with a small bladder in the Adriamycin rat model occurs following Adriamycin administration on gestational days 7-9. This simple experimental model of bilateral megaureter may allow further research into the pathophysiology of this condition.

Objective: Hemorrhagic cystitis is a well-known complication of cyclophosphamide therapy but extensive involvement of the entire urinary tract is far less common. We report here a patient who developed severe hemorrhagic pyelitis, ureteritis, and cystitis after one cycle of cyclophosphamide-containing combination chemotherapy., Method: A patient with synchronous carcinoma of the ovary and the uterus developed severe hemorrhagic pyelitis, ureteritis, and cystitis leading to bilateral hydronephroses and acute renal failure after one cycle of combination chemotherapy containing cyclophosphamide. The blood clots in the upper urinary tract were aspirated endoscopically and bilateral internal ureteric stents were inserted., Result: She underwent a prolonged diuretic phase with several episodes of hypokalemia, hypomagnesemia, and hypocalcemia and required intensive fluid and electrolytes replacement. Subsequently, she recovered fully with the ureteric stents removed 26 days later., Conclusion: In contrast to previous reports, where 2.8 g of cyclophosphamide was estimated to be the minimum cumulative dose required to cause hemorrhagic cystitis, this case illustrates that severe hemorrhagic complication can occur even after a low dose of cyclophosphamide (600 mg/m(2), total dose of 846 mg). Prompt diagnosis and intervention may be life-saving., (Copyright 2000 Academic Press.)

Two HIV seropositive patients receiving sulfadiazine for presumed cerebral toxoplasmosis who developed an obstructive nephropathy are described. Ultrasound examination showed respectively a bilateral hydro-ureteronephrosis in one patient and unilateral hydro-ureteronephrosis in the other. The obstructive nephropathy resolved in both patients with alkalic hydration and discontinuation of the sulfadiazine.

Objective: Evaluation of the treatment of complicated ureteric stones in patients treated with indinavir., Patients and Methods: From March 1997 to May 1998, 10 patients (7 males, 3 females, aged 30 to 56 years), treated by triple combination therapy for HIV infection, were drained for stones attributed to indinavir (CRIXIVAN), which had become obstructive and complicated. The duration of treatment with indinavir ranged from 14 days to 2 years. No patient had a history of urological disease. One patient presented with bilateral stones. All patients presented complicated clinical features: fever in 3 cases; severe pain in 8 cases, with delayed excretion more than 4 hours on IVU in 6 cases. All stones were radiolucent except for one slightly radioopaque stone. The stone was situated in the lumbar ureter in 3 cases, iliac ureter in 1 case and pelvic ureter in 8 cases., Results: In 10 out of 11 cases, a double J stent was inserted, preceded by drainage by simple ureteric catheter (infected urine) in 1 case and by percutaneous nephrostomy (PCN) with antegrade insertion of the stent (failure of the retrograde route) in 1 case. No complementary stone fragmentation or extraction treatment was necessary after this procedure. Stents were left in place for 3 to 7 weeks. In one case, a stone of the lumbar ureter required PCN followed by extracorporeal lithotripsy., Conclusion: In the case of complications requiring a urological procedure, insertion of a double J stent allows curative treatment of very friable indinavir stones, which are fragmented by passage of the stent.

Submucosal hemorrhage of the ureters, are a very uncommon quoted cause of hematuria when overdosing anticoagulants. We report two cases, CT shows some very typical aspects but can also highlight, as reported formerly, another associated complication: parietal hematoma of the small bowel.

This study tests the hypothesis that prenatal exposure to 2,4-dichlorophenyl-p-nitrophenyl ether (nitrofen), an herbicide known to induce pulmonary hypoplasia and other malformations in fetal rats, also may induce ureterohydronephrosis (UHN) and oligohydramnios. Time-dated pregnant Wistar rats were given 100 mg of the chemical on day 9 or 11 of gestation, and the findings in their fetuses were compared with those of suitable controls. Marked bilateral UHN was found in the majority of exposed fetuses, but without evidence of either mechanical obstruction or dysplastic parenchymal lesions. These animals had various degrees of lung hypoplasia. The amount of fluid in their amniotic sacs was increased rather than decreased and it was independent of lung weight but correlated to some extent with UHN grade. Urinary tract dilatation and polyhydramnios in this model most likely are attributable to polyuria caused by nitrofen-induced impairment of renal concentrating capacity. This relatively simple animal model might facilitate research into some aspects of the physiology of nonobstructive, prenatally dilated urinary tracts.

Based on two cases of correction of vesicoureteric reflux by endoscopic Teflon injection associated with a marked foreign body reaction, the authors analyse the tolerance of this substance for this type of treatment. On reviewing 29 cases of reflux, they found 3 failures (10%) of the method with 2 foreign body granulomas (7%). These complications, related to the use of Teflon, have been rarely reported in the literature, which essentially refers to the risks of migration of Teflon.

A 29-year-old woman suffered fatal hemorrhagic pyelitis, ureteritis and cystitis after receiving 4,800 mg./m.2 cyclophosphamide in preparation for marrow transplantation despite intravenous hydration and a Foley catheter. Cyclophosphamide-induced urothelial damage is not limited to the bladder and upper tract monitoring also is necessary.

Morphology, frequency and significance of capillary sclerosis (CS) in the ureter and electron microscopic findings in early papillary necrosis are described. CS of the urinary tract is characterized by a thickening of the basement membrane of capillaries lying just underneath the urothelium. The basement membrane changes can be demonstrated by PAS, Sudan stain and autofluorescence with equal reliability. By electron microscopy the thickened basement membranes exhibit a tree ring like pattern permeated by lipid vacuoles. CS is most often present in the renal pelvis and the ureter and only in particularly severe cases also in the urinary bladder. The most severe CS is found in the proximal and middle third of the ureter. In a prospective autopsy study CS was found in 3.5% of autopsies of adults and in 83% of clinically recognized phenacetin abusers. Since there is no association with other renal or metabolic diseases, CS can be considered as specific for phenacetin abuse. This finding is further substantiated by a significant correlation between the degree of severity of capillary sclerosis and the daily dose of phenacetin in grams. In about half of the patients with known analgesic abuse but without CS, possible causes for the lack of CS can be identified, of which the most important is regression of CS after stopping the abuse. Electron microscopic studies of early papillary necrosis show the same BM changes as in the ureter in peritubular capillaries, loops of Henle and similar BM alterations in the collecting ducts. The morphologic findings in the ureter and in the renal papilla suggest that CS in papillary necrosis are the consequence of a toxic damage of endothelial and in the kidney of endothelial and epithelial cells.

Intravesical formalin instillation has been performed in a patient with massive bladder hemorrhage secondary to radiation cystitis. Stricture formation at the level of the calyceal infundibula occurred, as well as retroperitoneal and ureteric fibrosis. The literature concerning formalin therapy is reviewed.

A patient was referred for evaluation of obstructive uropathy after treatment with 10% formalin to control recurrent hemorrhagic radiation cystitis. Progressive bilateral ureteral, pelvic, and renal parenchymal destruction occurred despite ileal ureteral replacement. This complication of therapy reinforces the concept that vesical instillation of formalin should be done only in extreme cases and then only in low concentrations.

A review of medical literature concerning case history reports of adverse clinical manifestations of hormonal contraceptives is presented. While extremely rare, these side-effects often present with obscure etiology, and the physician is cautioned to be aware of their occurrence.

Since previous literature suggested that estrogen-treated male mice are models for human benign prostatic hypertrophy, a series of studies was designed to examine urine retention and urogenital tract changes in rodents given chronic estradiol-17 beta (E) and dihydrotestosterone (DHT) treatments. In Study 1, intact and castrate male mice received E, DHT or E plus DHT for four weeks via subcutaneous Silastic capsules. Bladder urine volume increased in the groups given E and this effect was not altered by castration, DHT or removal of E capsules two weeks before necropsy. Estrogen treatment also increased mortality. In Study 2, intact male, intact female, adrenalectomized (Adx) male and sham Adx male mice received 16 weeks of steroid treatments. Bladder urine volume increased in all E treated groups regardless of sex or Adx. Hydronephrosis, hydroureter and increased mortality were found in the E treated mice of both sexes. Estrogen induced epithelial changes and edema of the prostate, vas deferens and the utriculus prostaticus. In further studies male rats, hamsters and guinea pigs were given several different dosages of E but no evidence of urine retention or increased mortality was found. Taken together these studies suggest that E-induced urine retention is unique to mice. Although urine retention and hydronephrosis found in the mice were similar to those in humans with BPH, the lesion that results in the urine obstruction is not similar.

Two patients were treated with Partusisten and Isoptin to inhibit uterine contractions. One patient was in the 36th and the other in the 32th week of pregnancy. Both developed colic like complaints related to the urogenital system, which disappeared after disruption of treatment and reoccured after restarting. The case description seemed to indicate an as yet not described side reaction of Partusisten.

A case of ureteral fibrosis complicating Clorpactin WCS90 treatment for interstitial cystitis in a patient with vesicoureteral reflux is presented. The results of a laboratory experiment designed to study the effects of Clorpactin WCS90 on refluxing ureters are discussed.

Results of formalin therapy for hemorrhage owing to post-radiation cystitis have been studied with special reference to the frequency and severity of ureteral complications. Gross bleeding stopped in 25 of 27 patients within 48 hours. However, 5 patients became anuric immediately after the instillation and in another 7 patients a transient increase in the serum creatinine level was observed. Urinary diversion was necessary in 11 of the 27 patients. The complication rate in the present study is considerably higher than reported previously. Complications may be explained by vesicoureteral reflux of a too strong formalin-alcohol solution. To avoid future complications we suggest that 1) a high diuresis should be induced peroperatively, 2) a 1 to 2 per cent formalin solution without alcohol should be used and 3) the instillation pressure should not exceed 15 cm. water.

The etiology of pyeloureteritis cystica has long been attributed to chronic infection and inflammation. A case is presented that is unique in that the acute onset and the rapid resolution of pyeloureteral filling defects in this patient were documented by radiography. There is no evidence of antecedent or concurrent infection in this patient. The disease occurred subsequent to the initiation of heparin therapy for suspected pelvic thrombophlebitis and cleared rapidly subsequent to its discontinuation. The rate of resolution of the radiographic findings may be helpful in distinguishing between true pyeloureteritis cystica and submucosal hemorrhage.

Hemorrhagic cystitis and ureteritis, and interstitial nephritis developed in a patient receiving penicillin G and streptomycin as therapy for bacterial endocarditis. After therapy was changed to vancomycin there was prompt resolution of these abnormalities.

The possible connection between long continued oestrogen intake and dilatation of the upper urinary tract was examined urographically in nine female rabbits. The degree of dilatation was judged on eleven parameters. The results of the study indicate that oestrogens without simultaneous mechanical influence on the urinary tract does not lead to dilatation of the pelvis or ureter. The results are illustrated graphically and are compared with the findings in the literature.

A case is presented in which ureteritis cystica developed following formalin instillation for treatment of cyclophosphamide-induced hemorrhagic cystitis. It is not known whether this complication, not previously reported, is a result of the cyclophosphamide, the formalin, or a combination of both. Patients being considered for formalin instillation should be studied by cystography for evaluation of vesicoureteral reflux. Alternative methods to formalin instillation should be considered in patients with reflux.

In an attempt to objectively evaluate the biocompatibility of materials commonly used for ureteral stenting, stent-catheters made of four different materials were placed randomly in 31 ureters of 19 mongrel dogs. Animals underwent urography at four weeks and were sacrificed at six weeks. Mild hydronephrosis was noted in eight instances, essentially unrelated to specific material. Silicone, C-flex and polyurethane stents caused a similar, mild degree of ureteral edema, but ureters stented with Silitek demonstrated fairly marked edema. Epithelial ulceration and erosion, often severe, occurred with all polyurethane stents, and rarely with the three other materials. All materials differed statistically from controls, and C-flex caused less reaction overall than polyurethane, indicating differences in biocompatibility of the various materials which may be relevant to their use in patients undergoing long-term ureteral stenting. In practical terms, these suggest that certain materials, notably silicone and C-flex, are more suitable for ureteral stenting than others.

The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.

Six nulliparous patients were found to have overdistensiblity of the upper urinary tract on excretion urography. Of these five had had persistent or recurrent urinary infections. All had been or were receiving oral contraceptives. Though overdistensibility associated with contraceptive therapy is unlikely to be life-threatening, it may be associated with increased patient morbidity.