Xanthine crystals induced by topiroxostat, a xanthine oxidoreductase inhibitor, in rats, cause transitional cell tumors.

The present study was performed to elucidate the underlying mechanism of transitional cell tumors found in the carcinogenicity testing of topiroxostat, a xanthine oxidoreductase inhibitor, in which topiroxostat was orally given to F344 rats at 0.3, 1, and 3 mg/kg for 2 years. In the urinary bladder, transitional cell papillomas and/or carcinomas were seen in males receiving 0.3, 1, and 3 mg/kg (1/49, 3/49, and 10/50, respectively). In the kidney, transitional cell papillomas and/or carcinomas in the pelvis were seen in 2/50 males and 1/50 females receiving 3 mg/kg. In the mechanistic study by 52-week oral treatment with topiroxostat at 3 mg/kg to F344 male rats, with and without citrate, simple and papillary transitional cell hyperplasias of the urinary bladder epithelium were observed in 5/17 in the topiroxostat-alone treatment group, along with xanthine-induced nephropathy, in contrast to neither xanthine crystals nor lesions in urinary organs by co-treatment group with citrate. As for sex differences of urinary bladder tumors, the BrdU labeling index for epithelial cells of the urinary bladder by 5-week oral treatment with topiroxostat at 10 mg/kg to F344 rats was increased in males only, showing consistency with histopathological findings. Therefore, the present study indicates that transitional cell tumors induced by topiroxostat in rats were due to physical stimulation to transitional cells of xanthine crystals/calculi and provides that other factors were not implicated in this tumorigenesis. Furthermore, the present study suggests that such tumors do not predict for humans since topiroxostat-induced xanthine deposition is a rodent-specific event.

Mechanical lithotripsy of pancreatic and biliary stones: complications and available treatment options collected from expert centers.

INTRODUCTION: PD and common bile duct (CBD) stones often require mechanical lithotripsy (ML) at ERCP for successful extraction. The frequency and spectrum of complications is not well described in the literature. AIM: To describe the frequency and spectrum of complications of ML. METHODS: A comprehensive retrospective review of cases requiring ML of large or resistant PC and/or CBD stones using a 46-point data questionnaire on type(s) of complication, treatment attempted, and success of treatment. The study involved 7 tertiary referral centers with 712 ML cases (643 biliary and 69 pancreatic). RESULTS: Overall incidence of complications were: 4-4% (31/712); 23/643 biliary, 8/69 pancreatic; 21 single, 10 multiple. Biliary complications: trapped (TR)/broken (BR) basket (N = 11), wire fracture (FX) (N = 8), broken (BR) handle (N = 7), perforation/duct injury (N = 3). Pancreatic complications: TR/BR basket (N = 7), wire FX (N = 4), BR handle (N = 5), pancreatic duct leak (N = 1). Endoscopic intervention successfully treated complications in 29/31 cases (93.5%). Biliary group treatments: sphincterotomy (ES) extension (N = 7), electrohydraulic lithotripsy (EHL) (N = 11), stent (N = 3), per-oral Soehendra lithotripsy (N = 8), surgery (N = 1), extracorporeal lithotripsy (N = 5), and dislodge stones/change basket (N = 4). Pancreatic group treatments: ES extension (N = 3), EHL (N = 2), stent (N = 5), Soehendra lithotriptor (N = 4), dislodge stones/change basket (N = 2), extracorporeal lithotripsy (ECL) (N = 1), surgery (N = 1). Perforated viscus patient died at 30 days. CONCLUSION: The majority of ML in expert centers involved the bile duct. The complication rate of pancreatic ML is threefold greater than biliary lithotripsy. The most frequent complication of biliary and pancreatic ML is trapped/broken baskets. Extension of ES and EHL are the most frequently utilized treatment options.

Gallbladder and urinary tract precipitations associated with ceftriaxone therapy in children: a prospective study.

The incidence and outcome of gallbladder and urinary tract complications in children receiving ceftriaxone therapy were evaluated prospectively. The subjects were given intravenous ceftriaxone, 100 mg/kg/day, in two divided doses infused over 20-30-minute periods, for 5-14 days. Serial abdominal ultrasonography revealed gallbladder and urinary tract precipitations in five of 35 children, three of whom had gallbladder pseudolithiasis, one gallbladder sludge and one gallbladder pseudolithiasis and urinary bladder sludge. The children who had gallbladder sludge and gallbladder pseudolithiasis with urinary bladder sludge had abdominal pain, nausea and vomiting. Three children remained symptom-free. The gallbladder precipitations were found after 4-9 days of ceftriaxone therapy, and resolved completely 7-19 days after the end of treatment. The urinary tract precipitation was found on the 5th day after cessation of ceftriaxone therapy and resolved 7 days later. Ceftriaxone-associated gallbladder pseudolithiasis, gallbladder sludge and urinary bladder sludge usually resolve spontaneously and physicians should be aware of these complications so as to avoid unnecessary therapeutic procedures.

Electron microscopic detection of tin accumulation in biliopancreatic concrements after induction of chronic pancreatitis in rats by di-n-butyltin dichloride.

The organotin compound di-n-butyltin dichloride (DBTC) is able to induce an acute and later a chronic pancreatitis in rats. In previous papers the authors demonstrated this DBTC pancreatitis as a rat model for an interstitial pancreatitis with tendency to transduction to the chronic form. DBTC is excreted according to its lipophilic nature by liver and bile. Therefore, the bilio-pancreatic main duct is necrotized by the tin-loaded bile. The duct system is blocked by cell debris and later by epithelial proliferations. In the chronic phase, numerous rats develop concrements in the main duct. In the present paper, the authors report about bacterial growth in some bilio-pancreatic concrements. Whereas the electron microscopic detection of tin by energy-dispersive X-ray analysis (EDX) in SEM or electron energy loss spectroscopy (EELS) in TEM was negative in the parenchyma of pancreas and liver, some concrements with bacterial cells were positive for this element. Tin mapping with energy spectroscopic imaging (ESI) in TEM demonstrated the congruency of tin signals and electron-dense particles inside these bacteria and of electron-dense accumulations in the matrix of these concrements. The low content of tin in pancreatic and liver tissue and the higher quantity of tin inside the bacterial contaminated concrements were supported by atomic absorption spectrophotometry (AAS). The paper discusses the long time preservation of tin in the concrements as an action of heavy-metal- accumulating bacteria, which should be classified in the future by bacteriological methods.

Clinical pharmacology of furosemide in children: a supplement.

Furosemide is one of the most effective and least toxic diuretics used in pediatric practice. Experimental and clinical data suggest that adrenocorticosteroids and/or endogenous ouabain-like substances may play an important role in its diuretic effect. Also, the drug appears to have anti-inflammatory properties. In children with different diseases who received orally or intravenously 1 to 2 mg/kg doses of furosemide, a statistically significant positive linear relationship was found between the drug urinary excretion rate and the urine flow rate, but log dose-response curves to the drug were found to vary depending on the disease and the route of the drug administration. No sigmoid-shaped log dose-response curve (ie, one approaching a zero response at very low furosemide urinary excretion rates and a maximum response at very high excretion rates) was attained, which may suggest that the capacity of the kidney tubules to respond diuretically to the aforementioned doses of furosemide was not exceeded in these patients. However, in infants with different diseases and reasonably normal renal function who required administration of this diuretic, a very steep log dose-response curve to a 1 mg/kg intravenous dose of furosemide was found, which may suggest that higher doses may not result in a significant increase in diuretic response. The lowest mean furosemide urinary excretion rate and its concentration in urine associated with a significant diuresis were found to be 0.58 +/- 0.33 microg/kg/min and 24.2 +/- 10.5 microg/ml, respectively. Also, a significant correlation was found between the amount (in milligrams) of furosemide excreted in the urine during the first 6 hours after administration and the urine volume collected during that time. Patients with cystic fibrosis appeared to have a markedly more pronounced diuretic response to the average oral dose of 0.835 +/- 0.18 mg/kg than that reported in control children given 2 mg/kg. In children with acute renal failure caused by acute gastroenterocolitis or glomerulonephritis, a broad relationship was observed between a single intravenous dose and diuretic response after administration of furosemide (1.2 to 30.8 mg/kg). It was suggested that the total daily dose of the drug should not exceed 100 mg in these patients. Furosemide was found to be effective in management of bronchoconstriction accompanying chronic lung disease and narrowing of the upper respiratory airways; in hydrocephalus in infancy to avoid cerebrospinal fluid shunts; in some diagnostic procedures, such as an assessment of fetal and neonatal hydronephrosis; and in evaluation of different types of renal tubular acidosis. Among side effects accompanying clinical use of this drug were cholelithiasis in premature infants receiving total parenteral nutrition concomitantly with the diuretic; secondary hyperparathyroidism and bone disease in infants obtaining long-term furosemide treatment; and drug-induced fever.

Colon ischaemia secondary to barolith obstruction.

A case is described of an elderly woman who developed an obstructing barolith in the sigmoid colon following a barium enema. Colonic ischaemia developed in the proximal colon. Predispositions and prevention of baroliths are discussed.

Pigment cholelithiasis induced by vitamin A and its prevencion by butylated hydroxytoluene

We previously reported on the induction by vitamin A of gallstones, rich in calcium and phosphate, in hamsters. On the other hand, it has been reported that the phenolic antioxidant butylate hydroxytoluene (BHT) potentiates the hepatotoxicity of vitamin A. In the present work we have tested the effect of BHT on the lithogenicity of vitamin A and on bile composition. The urinary excretion of calcium and phosphate was determined to assess a possible asymptomatic bone resorptin due to vitamin A toxicity, and/or an effect of BHT on the homeostasis of calcium and phosphate. Theree groups of 18 male hamsters were fed with the following diets for 70 days: Group 1, Purina Nutricubes (DB); Group 2, DB + 25,000 IU percent retinol acetate (DL); group 3, DL + 500 mg percent BHT. Vitamin A (group 2) induced gallstones in 78 percent of the animals, increased bile flow and biliary phosphate and calcium concentrations, and reduced those of bili salt, cholesterol and phospholipid. BHT (Group 3) reduced gallstone frequency to 5.5 percent, and decreased biliary phosphate, calcium and lipids toward more normal concentrations. Vitamin A alone or with BHT did not significantly affect food intake or urinary excretion of calcium and phosphate

Massive ingestion of sustained-release verapamil with a concretion and bowel infarction.

Gastric concretions secondary to a drug overdose are uncommon but potentially fatal if not recognized and treated. They may continue to release drug into the stomach for hours or days after the ingestion, complicating diagnosis and treatment. We describe the case of a man with the previously unreported association of bowel infarction with a verapamil ingestion and concretion. This case illustrates the need for a heightened awareness of this potential complication.

Incarcerated bariolith of the cecum eight months after a barium meal.

Barioliths consist of inspissated barium mixed with feces. They are a rare complication after barium contrast roentgenography and occur almost exclusively in the large bowel. Mostly asymptomatic or causing only slight symptoms and signs, they may persist for months or years. We report a severe case of cecal bariolith. Clinical symptoms and signs, radiological findings, intraoperative findings, and histology are presented and discussed with reference to the literature.

[Inhibitory action of diphosphonate on the development of pancreatic concrements (experiment with EHDP (author's transl)]. / Diphosphonat als Inhibitor einer Konkrementbildung im Pankreas (Tierversuche mit AHDP).

The application of the diphosphonate EHDP (ethane-I-hydroxy-I,I-diphosphonate) prior to the commencement of a calciphylactic experiment (SELYE) inhibits the interstitial calcification and fixation of apatite in the pancreas of female rats (dosage: 20 mgEHDP i. p. per 150 g body mass). Thus the inhibitory potency of EHDP on soft tissue calcification is confirmed. Previously, on the basis of experimental results, a therapeutic administration of this substance in the field of clinical pancreatology could not be derived because the most of human intraductal calculi is composed of calcium carbonate.

A comparative evaluation of Avitene and gelfoam for hemostasis in experimental canine prostatic wounds.

Microcrystalline collagen has been reported to be an effective hemostatic agent in brain, liver, kidney, etc. This experimental study in dogs and rats shows that microcrystalline collagen is a more effective hemostat in prostatic hemorrhage than is purified gelatin solution. No gross or histologic evidence of tissue damage or calcification was induced by microcrystalline collagen or purified gelatin solution. Wafers of microcrystalline collagen that are placed in rat bladders dissolve and do not induce calculogenesis.