Initial presentation in psychiatry emergency room led to diagnosis of many urinary bladder stones in a male patient.

The first case of man who presented to psychiatry emergency room for evaluation of abnormal behavior because of urinary stones was reported. Careful evaluation of patient led to a diagnosis of 37 urinary bladder stones in an Egyptian man with obstructive uropathy and metabolic defects in the form of hyperoxaluria and hypocitraturia. Knowledge of the differential diagnosis of metabolic defects can lead to successful outcome in preventing reformation of urinary tract stones after surgery. A 61-year-old Egyptian man presented to psychiatry emergency room because he was found lying on floor in bathroom to urinate by his wife who thought her husband needed psychiatric evaluation. Patient gave history of frequent urination and dysuria on and off for 3 years. In the last 3 months before his presentation to emergency room, he got into a habit of lying down on his left side when he went to bathroom to urinate because it was easier for him to pass urine. Renal consultation requested because of presence of red blood cells in urinalysis. Computed tomography of the abdomen and pelvis showed bilateral hydronephrosis and multiple bladder stones. Twenty-four-hour urine collection showed low urinary citrate and high oxalate. Patient underwent open vesicolithotomy and removal of 36 stones. Stone analysis showed 75% uric acid and 25% calcium oxalate. Patient did very well after surgery, and 1 month later, he underwent transuretheral resection of prostate without any complications. Now patient has no difficulty passing urine and he has no recent attack of urinary tract infection. Knowledge of the differential diagnosis of metabolic defects in men with urinary bladder stones would hopefully provide clinicians with the proper diagnostic tools to more specifically treat such patients with improved success in preventing reformation of urinary tract stones after surgery.

Single-cell RNAseq and longitudinal proteomic analysis of a novel semi-spontaneous urothelial cancer model reveals tumor cell heterogeneity and pretumoral urine protein alterations.

Bladder cancer, one of the most prevalent malignancies worldwide, remains hard to classify due to a staggering molecular complexity. Despite a plethora of diagnostic tools and therapies, it is hard to outline the key steps leading up to the transition from high-risk non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC). Carcinogen-induced murine models can recapitulate urothelial carcinogenesis and natural anti-tumor immunity. Herein, we have developed and profiled a novel model of progressive NMIBC based on 10 weeks of OH-BBN exposure in hepatocyte growth factor/cyclin dependent kinase 4 (R24C) (Hgf-Cdk4R24C) mice. The profiling of the model was performed by histology grading, single cell transcriptomic and proteomic analysis, while the derivation of a tumorigenic cell line was validated and used to assess in vivo anti-tumor effects in response to immunotherapy. Established NMIBC was present in females at 10 weeks post OH-BBN exposure while neoplasia was not as advanced in male mice, however all mice progressed to MIBC. Single cell RNA sequencing analysis revealed an intratumoral heterogeneity also described in the human disease trajectory. Moreover, although immune activation biomarkers were elevated in urine during carcinogen exposure, anti-programmed cell death protein 1 (anti-PD1) monotherapy did not prevent tumor progression. Furthermore, anti-PD1 immunotherapy did not control the growth of subcutaneous tumors formed by the newly derived urothelial cancer cell line. However, treatment with CpG-oligodeoxynucleotides (ODN) significantly decreased tumor volume, but only in females. In conclusion, the molecular map of this novel preclinical model of bladder cancer provides an opportunity to further investigate pharmacological therapies ahead with regards to both targeted drugs and immunotherapies to improve the strategies of how we should tackle the heterogeneous tumor microenvironment in urothelial bladder cancer to improve responses rates in the clinic.

The effect of pumpkin seeds on oxalcrystalluria and urinary compositions of children in hyperendemic area.

We investigated the effect of pumpkin-seed supplementation on oxalcrystalluria and urinary composition in 20 boys age 2-7 yr from a hyperendemic area of Ubol province in Thailand. The experiment had four periods: control (before treatment), oxalate supplementation 5mg X kg-1 body wt X day-1, pumpkin-seed or orthophosphate supplementation 60 mg X kg body wt-1 X day-1, and posttreatment. Causal morning and 24-h urines were collected analyzed for crystalluria, pH, calcium, phosphorous, oxalate, creatinine, sodium, potassium, citrate glycosaminoglycans, and pyrophosphate. The results demonstrated that the longer the supplementation period of pumpkin seeds, the better were the results. Pumpkin seeds lowered calcium-oxalate crystal occurrence and calcium level but increased phosphorus, pyrophosphate, glycosaminoglycans, and potassium values in urine as compared with orthophosphate supplementation. Pumpkin seeds provide high phosphorus levels and can be used as a potential agent in lowering the risk of bladder-stone disease.

Rodent bladder tumors do not always predict for humans.

Dr. David Clayson, 20 years ago, suggested that chemicals which lead to the formation of calculi in rodents might pose an artifact with respect to extrapolation to potential carcinogenic risk to humans. We reviewed what has been learned about the role of calculi in urinary bladder carcinogenesis in the ensuing 20 years, along with several examples. Formation of microcrystalluria and amorphous precipitate also poses problems in interpretation and examples are described. The chemicals producing these solid urinary materials are non-genotoxic, with marked increase in cell proliferation being the mode of action by which they are able to produce cancer in long-term rodent bioassays.

Possible role for chondroitin sulfate in urolithiasis: in vivo studies in an experimental model.

The effect of chondroitin sulfate upon the growth of calcium oxalate crystals was measured in vivo by using an experimental model in rats. Adult male Wistar rats were treated by chronic i.p. injections of chondroitin sulfate solutions (1, 5 or 10 mg in 0.3 ml of saline, every 2 days). This treatment led to a dose-dependent increase in the urinary chondroitin sulfate concentration. Urolithiasis was induced by the introduction of a calcium oxalate seed into the bladder of the animals. Urine samples were collected and the calculi formed were removed after 42 days. The chondroitin sulfate concentration have decreased in the lithiasic urines, as compared to controls and higher chondroitin sulfate doses correlated with larger calculi. The presence of chondroitin sulfate in the matrices of stones obtained from chondroitin sulfate-treated animals suggested that there was some adsorption of chondroitin sulfate on to the growth sites of the calcium oxalate crystals. In contrast to the chondroitin sulfate effect observed in vitro, which inhibits the growth of calcium oxalate crystals, our results suggest that in vivo chondroitin sulfate promotes the growth of stones in the urinary tract.

Relationships between some lithogenetic factors and vitamin B6-status in idiopathic calcium lithiasis.

Several researchers have shown that a reduced intake of vitamin B6 can induce increased oxalate urinary excretion leading to a higher incidence of calcium oxalate stones. Furthermore, the treatment with pyridoxine in patients with urinary stones and high oxalate excretion has led to contradictory results as the excretion of oxalate was either decreased, unchanged or increased. To verify if these divergent results were linked to a different B6 status of the patients undergoing the treatment, we studied the vitamin B6 and the main lithogenetic factor levels in patients with idiopathic calcium lithiasis as compared to normal subjects. The results showed that a high oxalate excretion is not necessarily coupled with a low vitamin B6 status and viceversa. However, some stone formers present a non homogeneous vitamin pattern that could be the consequence of an abnormal vitamin B6 metabolism.

Urinary constituents in an endemic area of stones and renal tubular acidosis in northeastern Thailand.

Nephrolithiasis and endemic renal distal tubular acidosis are common in northeastern Thailand. The etiology is still unknown. It is generally accepted that urine electrolytes influence the capacity of urine to inhibit or promote renal and also bladder stones. The purpose of this study was to analyse the composition of the urine in the indigenous population in the northeast area and compare their values with data obtained from a group of age matched adults, living in Bangkok. Twenty-four hour urine samples from 23 normal adult villagers from six villages within the province of Khon Kaen and 34 normal adults living in Bangkok were collected, and the daily excretion of creatinine, uric acid, calcium and inorganic phosphate, sodium, potassium, chloride, magnesium and oxalate were assayed. Daily urinary sodium, potassium, chloride and phosphate of the villagers were significantly lower than those of Bangkokians. No difference in the urinary excretion of calcium, magnesium, uric acid, oxalate and creatinine was found. The Na/Ca, and Ca/PO4 ratios of villagers were significantly lower than those of the Bangkok subjects. The villagers excreted significantly lower amounts of Na in the face of relatively higher urinary Ca. The above data, combined with our previous study showing the low values of urinary citrate in the villagers in the same areas, strongly indicate that the indigeneous population is at high risk in developing urolithiasis. The causes for these electrolyte abnormalities are still unknown. Low contents of the major electrolytes in their diets might play an important role. Low phosphate output indicates low protein diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Xanthine urolithiasis: ultrastructure analysis of renal and bladder calculi.

The surface structure of a xanthine stone from a patient with hereditary xanthinuria was examined using scanning electron microscopy. This revealed that the xanthine stone was composed of at least two very different structures. One was a spherical protrusion with craters and a fine granular surface and the other consisted of a granular growth of plate-like crystals.

Interdependence of urinary factors in calcareous bladder stone patients.

Twenty-four-hour urinary excretion of calcium, oxalic acid, inorganic phosphorus, magnesium and citric acid was examined in fifty-nine stone formers with bladder stones. Hypercalciuria and hyperoxaluria were present in 18.6% and 44.1%, respectively, while 11.9% of patients had both abnormalities. Hypomagnesuria and hypocitraturia were present in 67.8% and 69.5%, respectively, while 45.7% had both of these abnormalities. Normal urine chemistry in respect of parameters studied was observed only in 1.7% of cases. In 15.2% one risk factor was present, while 83.1% had two or more risk factors. "Path" analysis of the urinary parameters directly related to calcium lithiasis showed that magnesium and oxalic acid have substantial influence on calcium excretion, whereas citric acid had none. The influence of phosphorus did not provide any consistent trend.

Evaluation of Ammannia baccifera Linn. for antiurolithic activity in albino rats.

Ethanolic extract of A. baccifera was tested for its antiurolithic activity in male albino rats. Urinary stones were induced by implantation of zinc discs in the urinary bladder. The stones formed were mainly of magnesium ammonium phosphate with traces of calcium oxalate. Ethanolic extract of A. baccifera (2g/kg/day, po) was found to be effective in reducing the formation of stones as also in dissolving the pre-formed ones. There was a significant increase in the urinary excretion of calcium, magnesium and oxalate, four weeks after implantation of zinc discs. Treatment with A. baccifera has significantly reduced calcium and magnesium levels in the prophylactic group while it has reversed the levels of these ions to normal values in the curative group.

[Misdiagnosis of urinalysis due to in vivo formation of urinary stones]. / Fehlinterpretation von Urinanalysen durch in vivo wachsende Harnsteine.

The occurrence of biochemically unaltered urinalyses in patients with severe recurrent stone formation is not a rare observation in practice. The possible reasons for that phenomenon are manifold. We show that stone growth-related urinary depletion of lithogenic constituents caused by acute growth of urinary calculi in vivo can be an important reason for the observed phenomenon. The described process which can strongly influence the urinary composition occurs in any stone-bearing patient. Thus, it is strongly recommended that stone-related alterations be taken into account when interpreting the urinalyses of these patients. Based on simplified model assumptions, the extent of the expected chemical depletion effect can be calculated for any stone patient's urine sample. In two easy-to-use nomograms, we have combined the key parameters which govern the process, allowing the user a fast and easy estimation.

[An aged case of hereditary xanthinuria with xanthine urinary calculi].

A 74-year-old female with hereditary xanthinuria and xanthine stones is reported. She has a family history of consanguineous parents and a past history of right side nephrectomy due to a xanthine renal stone and vesicolithotomy of 3 bladder stones approximately 5 X 4 X 4 cm in size at the age of 58 and 71, respectively. Her young brother exhibited a slightly elevated urinary excretion of oxypurines. Laboratory examination showed a low serum level (0.3 mg/dl) and urinary excretion (1.56 mg/day) of uric acid, and high plasma and urine levels of oxypurines. No xanthine oxidase activity was detectably in duodenal mucosa by biopsy specimen obtained by duodenofiberscopy. Now she has another stone approximately 5 X 4 X 4 cm in her bladder. There have been are few elderly cases of hereditary xanthinuria with recurrent giant urolithiasis.

[Urinary trace elements excretion in patients with cystine calculosis]. / Wydalanie pierwiastków sladowych z moczem u chorych z kamica cystynowa.

UNLABELLED: Not all cystinuric patients develop urinary calculi. There is the need to identify modulating factors. In recent years the role of trace elements in the mechanism of stone formation has received a steadily increasing attention. The aim of our study was to determine urinary excretion of trace elements in patients with recurrent cystine calculosis. MATERIAL AND METHODS: 11 patients with recurrent cystine calculosis and 15 healthy volunteers participated in the study. Urinary zinc, copper, chromium, boron and arsenic concentrations were determined by use of inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: There was a statistically significant difference between the patients with cystinuria and controls in mean arsenic urinary excretion (0.625+/-0.6 microg/kg body weight/24 h vs. 1.264+/-0.635 microg/kg b.w./24 h, p=0.02). There was also a noticeable difference in urinary chromium, the mean concentration of which was higher in case of the patients with cystinuria (3.32+/-3.59 microg/kg/24 h) than in the controls (1.38+/-0.69 microg/kg/24 h). The mean urinary excretion of zinc, copper, and boron (in microg/kg b.w./24 h) were respectively 7.40+/-7.98; 1.33+/-0.48; 26.55+/-15.81 in the patients with cystinuria and 9.84+/-5.33; 1.16+/-0.84; 35.87+/-13.76 in the controls. CONCLUSION: It seems that a decreased excretion of arsenic may contribute to the development of cystine calculosis.

Preventive and therapeutic effects of sodium bicarbonate on melamine-induced bladder stones in mice.

The actual preventive and therapeutic effects of alkalinizing urine on melamine-induced bladder stones (cystolith) are not completely known. Using an ideal model, two experiments were conducted in Balb/c mice. The mice were fed a normal diet in controls and a melamine diet in the other groups. The first day was set as experiment-day 1. In "Experiment 1", either low-/mid-/high-dose sodium bicarbonate (SB) or sterile water was administered by intragastric perfusion (once daily) to the mice for 14 days. Relative to the model group, the mean pH of the urine in the SB groups was significantly elevated at 3 h after SB administration, with a significant decrease in cystolith incidence on experiment-day 14. In "Experiment 2", on experiment-day 12, the melamine diet was replaced by a normal diet in 4 groups with melamine withdrawal (MW). Meanwhile, either mid-/high-dose SB or sterile water was administered by intragastric perfusion (once) to the mice in the corresponding groups. On experiment-day 12, after an additional 8 h, the cystolith incidence was significantly reduced in the high-SB, MW + mid-SB and MW + high-SB groups than in the model group. In conclusion, low urinary pH is one of the main determinants of the formation of melamine-associated stones, urinary alkalinization can be achieved by a proper dose of oral SB, and SB acts to prevent and treat melamine-induced cystoliths in mice.