Evaluation of the Influence of a History of Childhood Nocturnal Enuresis on Nighttime Urinary Frequency and the Causes of Nocturia in Adults.

OBJECTIVE: To examine whether a history of nocturnal enuresis affects nighttime urinary frequency and to evaluate nocturia etiologies in adults. MATERIALS AND METHODS: A total of 143 participants with at least one episode of nocturia per night were included in this study. The self-reported questionnaire collected data on demographic characteristics, medical history, history of nocturnal enuresis in elementary school, lower urinary tract symptoms, and frequency-volume charts. RESULTS: A history of nocturnal enuresis was observed in 52.4% of participants. However, night-time urinary frequency was significantly lower in participants with a history of nocturnal enuresis in elementary school than in those without such history. On multivariate analysis, a history of nocturnal enuresis was also negatively associated with nighttime urinary frequency (P <.01). There was a collinearity effect between age and nighttime urinary frequency. A history of nocturnal enuresis did not affect the presence of nocturnal polyuria or overactive bladder in participants. However, sleep disturbances were fewer in participants with a history of nocturnal enuresis (odds ratio 0.404). CONCLUSION: A history of nocturnal enuresis might be negatively associated with nighttime urinary frequency due to fewer sleep disturbances. Further, progression of nocturia may depend on conditions, such as age and acquired diseases.

[A case of renal salt wasting syndrome progressing to severe hyponatremia after gemcitabine-cisplatin chemotherapy].

Renal impairment with a decreased glomerular filtration rate is a classical nephrotoxicity associated with cisplatin (CDDP). Renal salt wasting syndrome (RSWS), which is characterized by water and salt wasting, is a rare nephrotoxicity associated with CDDP. This syndrome shares many similarities with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Thus, it is important to differentiate between RSWS and SIADH because the treatment of one affects the pathogenesis of the other. Here, we report a case of RSWS after chemotherapy with CDDP. A 72-year-old man with bladder urothelial carcinoma (cT2N0M0) was admitted to our hospital for the first cycle of neoadjuvant chemotherapy with CDDP and gemcitabine. He was administered intravenous fluids on day 2 before chemotherapy. Five days later, he developed nausea, dysorexia, delirium, hyponatremia (serum sodium level 115 mEq/l), and renal dysfunction. Thus, we administered a normal saline infusion. Over the next 6 days, his serum sodium level increased to 137 mEq/l, and we stopped normal saline infusion. Three days after discontinuation of saline infusion, his serum sodium level again decreased to 128 mEq/l, and the next day, his systolic blood pressure dropped gradually between 70 and 80 mmHg. Therefore, we resumed the normal saline infusion, and after 3 days, his serum sodium level increased to 135 mEq/l and systolic blood pressure ranged between 110 and 130 mmHg. On the basis of dehydration and high urinary sodium excretion at the onset of chemotherapy, we diagnosed this clinical condition as RSWS. We abandoned neo-adjuvant chemotherapy, and performed total cystectomy and ileal conduit. Since 4 months after surgery, he has been free from recurrence and metastasis.

[A case of micropapillary bladder carcinoma].

A case of urothelial carcinoma containing micropapillary variant in the urinary bladder is reported. The micropapillary bladder carcinoma isa rare variant of urothelial carcinoma and has an aggressive clinical course. A 45-year-old man complained of hematuria in October, 2009. He visited a hospital and was diagnosed with a bladder tumor. Transurethral resection of the bladder tumor was performed at the hospital. The transurethral resection demonstrated poorly differentiated adenocarcinoma invading the bladder muscle layer. Then he consulted our hospital. Our pathologist diagnosed the case as micropapillary variant of urothelial carcinoma in the urinary bladder. Accordingly, radical cystectomy and pelvic lymph nodes dissection were performed. After the operation, he received three courses of gemcitabine and cisplatin as adjuvant chemotherapy. The patient remains free of tumor recurrence and metastasis for 28 months after the cystectomy.

[A case of interstitial pneumonia during gemcitabine and cisplatin chemotherapy for locally advanced bladder cancer].

A 76-year-old woman received chemotherapy with gemcitabine and cisplatin (GC therapy) for local advanced bladder cancer. She suffered from dyspnea on day 19 during the first course of GC therapy. Both chest X-ray and computed tomography (CT) images revealed diffuse bilateral interstitial infiltrates. She was diagnosed as having drug-induced interstitial pneumonia. We identified gemcitabine as the causative agent based on the results of examinations (CT, X-ray, KL-6 level, drug lymphocyte stimulation test (DLST)). After three months of steroid therapy, her interstitial pneumonia was completely resolved on CT scans. Although gemcitabine-induced interstitial pneumonia is a rare adverse event, it should be considered a severe complication because delayed diagnosis and treatment can lead to a fatal outcome. Thus, early detection of drug-induced interstitial pneumonia is extremely important during GC therapy.

[A case report of transurethral resection of eroding urethral mesh after a tension-free vaginal tape procedure].

A 72-year-old woman presented with lower urinary tract symptoms (incomplete voiding, voiding pain, and gross hematuria) 2 years after a tension-free vaginal tape (TVT) procedure for stress urinary incontinence. Cystoscopy revealed erosion of the urethra associated with a urethral stone attached to a polypropylene mesh. We performed transurethral resection of the polypropylene mesh and transurethral lithotripsy. After removal of the mesh, she had stress urinary incontinence but her symptoms resolved. Urethral erosion is a rare complication of TVT, and the method of handling the intrusive mesh has not been standardized. Transurethral endoscopic resection of the eroding mesh is a minimally invasive and successful procedure that should be considered for the treatment of this complication resulting from TVT.

[A case of complicated perioperative management of radical nephrectomy in a patient with a drug-eluting stent].

Drug-eluting stents (DES) are commonly used for coronary artery disease and patients with DES require antiplatelet therapy because of the risk of late stent thrombosis. Accordingly problems can occur in the perioperative period due to late thrombosis of a stent after discontinuation of antiplatelet therapy before surgery. A 64-year-old man was diagnosed as having a right renal tumor (T1aN0M0) and his performance status was 4. Three years earlier, a DES had been placed in a coronary artery and he was taking aspirin plus ticlopidine. These drugs were stopped at 7 days before surgery and we started heparin (15,000 U/day). Heparin was continued during and after radical nephrectomy. Although operative blood loss was only 178 ml, the amount of bleeding within 5 hours after surgery was 1,620 ml. The wound was re-opened, but there was no obvious bleeding source, so oozing from the muscle was controlled. His blood pressure dropped and cardiac arrest occurred at 22 hours after re-operation, but he was resuscitated with blood transfusion and the bleeding stopped after the dose of heparin was reduced. Three days after the operation, antiplatelet therapy was re-started and heparin was ceased at 10 days after surgery. The blood clot in the right retroperitoneal space formed an abscess at 28 days after radical nephrectomy. After drainage, the retroperitoneal space was washed twice a day for about 40 days. The wound healed, and he currently has no evidence of recurrence or metastasis and has no cardiac sequelae.

Skeletal-related events in urological cancer patients with bone metastasis: a multicenter study in Japan.

OBJECTIVE: To investigate the incidence of skeletal-related events (SRE) in urological cancer patients with bone metastases in Japan. METHODS: Five hundred eleven patients with urological cancer and documented bone metastases treated from January 2003 to April 2008 in ten Japanese institutions were included in a retrospective analysis. Type and incidence of SRE (fracture, radiotherapy, spinal cord compression, surgery, hypercalcemia, and bone pain) were determined from patient medical records. RESULTS: The overall incidence of SRE, including 'pain', was 61%. The most common event was radiotherapy for bone metastases, with an incidence of 31%. The overall incidence of events seemed to be similar among Japanese and Western patients with prostate cancer and renal cell carcinoma when comparing data with previously published reports. Nevertheless, a much lower incidence of fracture (19.1%) was observed in Japanese renal cell carcinoma patients. CONCLUSIONS: The overall incidence of SRE in Japanese urological cancer patients with bone metastasis was similar to that in Western patients, but the incidence of fracture was lower in Japanese renal cancer patients.

Changes of bladder activity and connexin 43-derived gap junctions after partial bladder-outlet obstruction in rats.

INTRODUCTION: We investigated changes of vesical gap junctions in relation to changes of the micturition reflex in rats with partial bladder-outlet obstruction (BOO). MATERIALS AND METHODS: A total of 66 female Sprague-Dawley rats were divided into six groups: sham operation (control); 3, 14, and 28 days after BOO; and 3 and 28 days after relief of BOO lasting for a three-day period. Under urethane anesthesia, isovolumetric cystometry was performed on each group. Expression of mRNA for the gap-junction protein connexin 43 (Cx43) in the bladder was measured in each group. Immunohistochemistry using Cx43 antibody was also performed on the bladder after BOO. RESULTS: The interval between bladder contractions was shorter in all of the other groups than in the control group. Expression of Cx43 mRNA was increased 3, 14, and 28 days after BOO (the peak increase was twofold), and three days after the relief of BOO, but it returned to the control level by 28 days after relief of BOO. Histologically, smooth muscle hypertrophy was detected in the bladder after BOO and punctate staining of the smooth muscle by Cx43 antibody increased after BOO. CONCLUSION: These results suggest that partial BOO produces detrusor overactivity that may depend on increased intercellular communication via gap junctions in the bladder. Relief of BOO led to a decrease of Cx43 mRNA, but detrusor overactivity persisted in the chronic phase, suggesting a reversible change of vesical gap junctions and an irreversible change of bladder activity after BOO.

Endogenous oxalogenesis after acute intravenous loading with ethylene glycol or glycine in rats receiving standard and vitamin B6-deficient diets.

OBJECTIVES: The effect on endogenous oxalate synthesis of acute intravenous loading with ethylene glycol or glycine was investigated in rats on a standard or a vitamin B6-deficient diet. METHODS: Twenty-four male Wistar rats weighing approximately 180 g were randomly divided into ethylene glycol and glycine groups of 12 animals each. These groups were further divided into two subgroups of six animals each that were fed either a standard or a vitamin B6-deficient diet for 3 weeks. Animals of these two subgroups received an intravenous infusion of 20 mg (322.22 micromol) of ethylene glycol or 100 mg (1332.09 micromol) of glycine, respectively. Urine samples were collected just before intravenous infusion of each substance and at hourly intervals until 5 h after receiving the infusion. Urinary oxalate, glycolate, and citrate levels were measured by capillary electrophoresis. RESULTS: Urinary oxalate and glycolate excretion was significantly increased after ethylene glycol administration. Significant differences between the control and vitamin B6-deficient groups were found. In contrast, there were only small changes of oxalate and glycolate excretion after glycine administration. Recovery of the given dose of ethylene glycol as oxalate in 5-h urine was 0.31% and 7.15% in the control and vitamin B6-deficient groups, respectively, whereas recovery of glycolate was 0.68% and 7.22%, respectively. CONCLUSIONS: Ethylene glycol loading has a significant effect on urinary oxalate excretion in both normal and vitamin B6-deficient rats, whereas glycine loading only has a small effect. Oxalate and glycolate excretion after ethylene glycol loading were respectively 23-fold and 11-fold higher in vitamin B6-deficient rats than in controls.

Calcium oxalate saturation in dialysis patients with and without primary hyperoxaluria.

Calcium oxalate supersaturation of the blood is associated with deposition of crystals in various tissues. We measured the serum levels of oxalate, citrate, calcium, and magnesium to estimate their saturation in 112 hemodialysis patients without primary hyperoxaluria and two boys with primary hyperoxaluria. Serum levels of oxalate and citrate were determined by high-performance capillary electrophoresis, while calcium and magnesium were measured by ICP spectroscopy. The serum levels of oxalate, citrate, calcium, and magnesium were 44.9+/-16.5, 138.1+/-54.9 micromol/l, 2.30+/-0.28, and 1.07+/-0.18 mmol/l, respectively, while the levels in patients with primary hyperoxaluria were 83.9+/-34.3, 197.9+/-63.5 micromol/l, 2.53+/-0.15, and 1.14+/-0.34 mmol/l, respectively. Serum calcium oxalate saturation (SS), as calculated by the Equil program, was significantly correlated with the serum oxalate level. Most patients showed metastable supersaturation (1

The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton.

Rap2 belongs to the Ras family of small GTP-binding proteins, but its specific roles in cell signaling remain unknown. In the present study, we have affinity-purified from rat brain a Rap2-interacting protein of approximately 155 kDa, p155. By liquid chromatography tandem mass spectrometry, we have identified p155 as Traf2- and Nck-interacting kinase (TNIK). TNIK possesses an N-terminal kinase domain homologous to STE20, the Saccharomyces cerevisiae mitogen-activated protein kinase kinase kinase kinase, and a C-terminal regulatory domain termed the citron homology (CNH) domain. TNIK induces disruption of F-actin structure, thereby inhibiting cell spreading. In addition, TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway. Among our observations, TNIK interacted with Rap2 through its CNH domain but did not interact with Rap1 or Ras. TNIK interaction with Rap2 was dependent on the intact effector region and GTP-bound configuration of Rap2. When co-expressed in cultured cells, TNIK colocalized with Rap2, while a mutant TNIK lacking the CNH domain did not. Rap2 potently enhanced the inhibitory function of TNIK against cell spreading, but this was not observed for the mutant TNIK lacking the CNH domain. Rap2 did not significantly enhance TNIK-induced JNK activation, but promoted autophosphorylation and translocation of TNIK to the detergent-insoluble cytoskeletal fraction. These results suggest that TNIK is a specific effector of Rap2 to regulate actin cytoskeleton.

Major factors modulating the serum oxalic acid level in hemodialysis patients.

Ascorbic acid overload and vitamin B6 deficiency have been implicated in the development of hyperoxalemia in dialysis patients, but there is still disagreement about this. Hemodialysis patients who are exposed long-term hyperoxalemia may develop secondary oxalosis with an increased risk of cardiac, vascular, and bone disease, and thus may benefit from maintaining a low serum oxalic acid level. In 452 hemodialysis patients, the serum level of oxalic acid was 47.2 +/- 22.9 micromol /l before and 16.9 +/- 10.5 micromol/l after a 4-hour dialysis session, while the ascorbic acid levels were 39.0 +/- 92.7 micromol/l and 6.5 +/- 18.6 micromol/l, the glycolic acid levels were 7.3 +/- 10.1 micromol/l and 0.6 +/- 2.3 micromol/l, and the citric acid levels were 141.3 +/- 54.7 micromol/l and 117.6 +/- 37.2 micromol/l, respectively. Most patients (65.3 percent) had low serum ascorbic acid levels (less than 10 micromol/l) before hemodialysis. The serum level of oxalic acid [Ox] showed a significant positive correlation with the levels of ascorbic acid [AA], glycolic acid [Gly], and creatinine [Cre]: [Ox] = 21.711 + 0.181 x [AA] + 0.174 x [Gly] + 0.171 x [Cre], (all micromol/l, p less than 0.05). In 124 dialysis patients, the 4-pyridoxic acid level was 8.9 +/- 19.6 micromol /l before and 3.9 +/- 8.8 micromol/l after dialysis, and it was not correlated with oxalic acid or glycolic acid. Most dialysis patients (65.3 percent) had low serum levels of ascorbic acid, but a subgroup of patients (12 percent) had high serum ascorbic acid levels (more than 100 micromol/l) associated with hyperoxalemia (88.2 +/- 24.5 micromol/l). High-dose vitamin C supplementation may aggravate hyperoxalemia in hemodialysis patients, so attention should be paid to avoiding this risk.

Mitogen-activated protein kinase kinase kinase kinase 4 as a putative effector of Rap2 to activate the c-Jun N-terminal kinase.

Little is known about the specific signaling roles of Rap2, a Ras family small GTP-binding protein. In a search for novel Rap2-interacting proteins by the yeast two-hybrid system, we isolated isoform 3 of the human mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), a previously described but uncharacterized isoform. Other isoforms of MAP4K4 in humans and mice are known as hematopoietic progenitor kinase (HPK)/germinal center kinase (GCK)-like kinase and Nck-interacting kinase, respectively. MAP4K4 belongs to the STE20 group of protein kinases and regulates c-Jun N-terminal kinase (JNK). MAP4K4 interacted with Rap2 through its C-terminal citron homology domain but did not interact with Rap1 or Ras. Interaction with Rap2 required the intact effector region of Rap2. MAP4K4 interacted preferentially with GTP-bound Rap2 over GDP-bound Rap2 in vitro. In cultured cells, MAP4K4 colocalized with Rap2, while a mutant MAP4K4 lacking the citron homology domain failed to do so. Furthermore, Rap2 enhanced MAP4K4-induced activation of JNK. These results suggest that MAP4K4 is a putative effector of Rap2 mediating the activation of JNK by Rap2.