Copper deficiency anemia due to zinc supplementation in a chronic hemodialysis patient.

Zinc deficiency causes dysgeusia and dermatitis as well as anemia. As approximately half of dialysis patients have zinc deficiency, zinc supplementation should be considered in case of erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia. We report a case of a chronic dialysis patient with copper deficiency anemia caused by standard-dose zinc supplementation. The patient was a 70-year-old woman who had received maintenance hemodialysis for 8 years due to diabetic nephropathy. She had been treated with weekly administration of darbepoetin 30 µg for renal anemia, which resulted in Hb 12 to 14 g/dL. She had no dysgeusia. When zinc deficiency (44 µg/dL) had been identified 4 months earlier, 50 mg daily zinc acetate hydrate (Nobelzin®), which is the standard dose, was started. Unexpectedly, her anemia progressed slowly with macrocytosis together with granulocytopenia. Her platelet count did not decrease at that time. Laboratory tests revealed a marked decrease of serum copper (< 4 µg/dL) and ceruloplasmin (< 2 mg/dL), although serum zinc was within the normal limit (125 µg/dL). We discontinued zinc acetate and started copper supplementation including cocoa for 1 month. Her anemia and granulocytopenia were dramatically restored coincident with the increase in both serum copper and ceruloplasmin. Copper supplementation also improved her iron status as assessed by transferrin saturation and ferritin. Clinicians should monitor both zinc and copper status in anemic dialysis patients during zinc supplementation, as both are important to drive normal hematopoiesis.

Machine learning-based computer-aided simple triage (CAST) for COVID-19 pneumonia as compared with triage by board-certified chest radiologists.

PURPOSE: Several reporting systems have been proposed for providing standardized language and diagnostic categories aiming for expressing the likelihood that lung abnormalities on CT images represent COVID-19. We developed a machine learning (ML)-based CT texture analysis software for simple triage based on the RSNA Expert Consensus Statement system. The purpose of this study was to conduct a multi-center and multi-reader study to determine the capability of ML-based computer-aided simple triage (CAST) software based on RSNA expert consensus statements for diagnosis of COVID-19 pneumonia. METHODS: For this multi-center study, 174 cases who had undergone CT and polymerase chain reaction (PCR) tests for COVID-19 were retrospectively included. Their CT data were then assessed by CAST and consensus from three board-certified chest radiologists, after which all cases were classified as either positive or negative. Diagnostic performance was then compared by McNemar's test. To determine radiological finding evaluation capability of CAST, three other board-certified chest radiologists assessed CAST results for radiological findings into five criteria. Finally, accuracies of all radiological evaluations were compared by McNemar's test. RESULTS: A comparison of diagnosis for COVID-19 pneumonia based on RT-PCR results for cases with COVID-19 pneumonia findings on CT showed no significant difference of diagnostic performance between ML-based CAST software and consensus evaluation (p > 0.05). Comparison of agreement on accuracy for all radiological finding evaluations showed that emphysema evaluation accuracy for investigator A (AC = 91.7%) was significantly lower than that for investigators B (100%, p = 0.0009) and C (100%, p = 0.0009). CONCLUSION: This multi-center study shows COVID-19 pneumonia triage by CAST can be considered at least as valid as that by chest expert radiologists and may be capable for playing as useful a complementary role for management of suspected COVID-19 pneumonia patients as well as the RT-PCR test in routine clinical practice.

Improving compliance with guidelines may lead to favorable clinical outcomes for patients with non-muscle-invasive bladder cancer: A retrospective multicenter study.

OBJECTIVES: Clinical guidelines recommend that patients with non-muscle-invasive bladder cancer (NMIBC) should be treated with appropriate adjuvant therapy. However, compliance with guideline recommendations is insufficient, and this may lead to unfavorable outcomes. We aimed to investigate the level of adherence to guideline recommendations in patients with NMIBC and evaluate the outcomes of those who did and did not receive guideline-recommended therapies. METHODS: We performed a retrospective analysis of patients with histologically diagnosed NMIBC. The percentage of patients with intermediate- and high-risk tumors who received adjuvant intravesical therapy or second transurethral resection (TUR) was calculated. Recurrence-free survival was assessed in patients who did and did not receive the therapies. We conducted a propensity score-matched analysis to compare outcomes between patients with intermediate-risk and T1 NMIBC who did and did not undergo guideline-recommended therapies. RESULTS: Overall, 1204 patients from the Tohoku Urological Evidence-Based Medicine Study Group and Kyoto University Hospital were included. Of patients with intermediate- and high-risk tumors, 91.0% and 74.0% did not receive maintenance bacillus Calmette-Guérin (BCG), respectively. In both groups, significantly better recurrence-free survival was found for patients treated with maintenance BCG. Among patients with T1 NMIBC, only 16.7% underwent guideline-recommended therapies, that is, a second TUR and maintenance BCG. Significantly greater recurrence-free survival was observed in patients who received guideline-recommended therapies compared with propensity-matched patients who did not. CONCLUSIONS: Guideline-recommended therapies may contribute to improvements in outcomes for patients with NMIBC, suggesting that improvements in adherence to clinical guidelines may lead to favorable outcomes.

A Bayesian estimation method for cerebral blood flow measurement by area-detector CT perfusion imaging.

PURPOSE: Bayesian estimation with advanced noise reduction (BEANR) in CT perfusion (CTP) could deliver more reliable cerebral blood flow (CBF) measurements than the commonly used reformulated singular value decomposition (rSVD). We compared the efficacy of CBF measurement by CTP using BEANR and rSVD, evaluating both relative to N-isopropyl-p-[(123) I]- iodoamphetamine (123I-IMP) single-photon emission computed tomography (SPECT) as a reference standard, in patients with cerebrovascular disease. METHODS: Thirty-one patients with suspected cerebrovascular disease underwent both CTP on a 320 detector-row CT system and SPECT. We applied rSVD and BEANR in the ischemic and contralateral regions to create CBF maps and calculate CBF ratios from the ischemic side to the healthy contralateral side (CBF index). The analysis involved comparing the CBF index between CTP methods and SPECT using Pearson's correlation and limits of agreement determined with Bland-Altman analyses, before comparing the mean difference in the CBF index between each CTP method and SPECT using the Wilcoxon matched pairs signed-rank test. RESULTS: The CBF indices of BEANR and 123I-IMP SPECT were significantly and positively correlated (r = 0.55, p < 0.0001), but there was no significant correlation between the rSVD method and SPECT (r = 0.15, p > 0.05). BEANR produced smaller limits of agreement for CBF than rSVD. The mean difference in the CBF index between BEANR and SPECT differed significantly from that between rSVD and SPECT (p < 0.001). CONCLUSIONS: BEANR has a better potential utility for CBF measurement in CTP than rSVD compared to SPECT in patients with cerebrovascular disease.

Single-incision laparoscopic totally extraperitoneal inguinal hernia repair with tumescent local anesthesia: report of more than 2000 procedures at a day-surgery clinic.

PURPOSE: The purpose of this study was to evaluate the feasibility and safety of single-incision laparoscopic surgery for totally extraperitoneal inguinal hernia repair (SILS-TEP) with tumescent local anesthesia (TLA) at a day-surgery clinic. METHODS: We analyzed, retrospectively, 2148 patients who underwent SILS-TEP under general anesthesia with TLA between April, 2015 and March, 2020 at Gi surgical clinic, to evaluate their operative outcomes. The TLA agent, consisting of normal saline and lidocaine with epinephrine and ropivacaine, was injected during surgery. RESULTS: The median operative times for unilateral and bilateral hernia were 50 min and 75 min, respectively. Blood loss was minimal in all patients. Conversion to the Lichtenstein method was required in 4% (91/2148) of patients. The median recovery room stay was 125 min and no analgesics were required in the recovery room by 75% (1613/2148) of the patients. All the patients left the clinic on the day of surgery. Complications developed in 6.5% (139/2148) of the patients, as seromas in 6% (125/2148), wound infections in 0.4% (8/2148), and hematomas in 0.2% (4/2148), respectively. Bowel injury and obstruction each occurred in 0.05% (1/2148) of the patients. There were no hernia recurrences. CONCLUSION: SILS-TEP with TLA can be performed safely at a day-surgery clinic.

Efficacy of early ureteral ligation on prevention of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: a prospective single-arm multicenter clinical trial.

OBJECTIVE: The rate of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma is high. Seeding upper urinary tract urothelial carcinoma cells onto the damaged bladder wall is considered to be one of the causes of intravesical recurrence after radical nephroureterectomy. We evaluated the utility of early ureteral ligation in preventing the intravesical recurrence. METHODS: This prospective single-arm clinical trial included patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma in the Tohoku Urological Evidence-Based Medicine Study Group between 2012 and 2013. Early ureteral ligation was defined as ligation of the ureter as quickly as possible after expanding the retroperitoneal space. A historical control was extracted from 454 patients who underwent radical nephroureterectomy in the same group, using propensity score-matched analysis. Intravesical recurrence-free survival rates were analyzed using Kaplan-Meier curves. Factors predicting intravesical recurrence were assessed using multivariate analyses. RESULTS: Seventy-four patients underwent early ureteral ligation. Seventeen (23%) patients had intravesical recurrence with a median follow-up period of 24 months. The 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 81% and 76%, and in the control group 75% and 63%, respectively (P = 0.160). In patients with renal pelvic cancer, the 1- and 2-year intravesical recurrence-free survival rates in the early ureteral ligation group were 89% and 86%, but in the control group 74% and 64%, respectively (P = 0.025). However, intravesical recurrence-free survival rates were similar in patients with ureteral cancer. Multivariate analyses of a subset of patients with renal pelvic cancer identified early ureteral ligation as an independent predictor of intravesical recurrence. CONCLUSIONS: Early ureteral ligation decreases the rate of intravesical recurrence after radical nephroureterectomy in patients with renal pelvic cancer. Thus, early ureteral ligation might help in prevention of intravesical recurrence for renal pelvic cancer.

Renal epithelioid angiomyolipoma with malignant features: Histological evaluation and novel immunohistochemical findings.

Renal epithelioid angiomyolipoma (EAML) is a potentially malignant tumor type whose characteristics and biomarkers predictive of malignant behavior have not been elucidated. Here, we report three cases of renal EAML with malignant features but without histories of tuberous sclerosis complex. Case 1 involved a 29-year-old man with a 12-cm solid mass in the right kidney who underwent radical right nephrectomy. Case 2 involved a 22-year-old woman with a retroperitoneal mass who underwent radical right nephrectomy and retroperitoneal tumorectomy. Local recurrence was detected 7 years post-surgery. Case 3 involved a 23-year-old man with a 14-cm solid mass in the left kidney who underwent radical left nephrectomy. Microscopically, the tumors in all cases demonstrated proliferation of epithelioid cells with atypia, mitotic activity, necrosis, hemorrhage, and vascular invasion. Epithelioid cells in all cases were immunohistochemically positive for melanocytic and myoid markers and weakly positive for E-cadherin and ß-catenin. Immunohistochemistry revealed activation of the mammalian target of rapamycin pathway. Here, we report the morphological and immunohistochemical features of clinically or histologically malignant renal EAML.

The effects of super-flux (high performance) dialyzer on plasma glycosylated pro-B-type natriuretic peptide (proBNP) and glycosylated N-Terminal proBNP in end-stage renal disease patients on dialysis.

BACKGROUND: Plasma BNP levels are predictive of prognosis in hemodialysis patients. However, recent studies showed that the current BNP immunoassay cross-reacts with glycosylated proBNP, and the NT-proBNP assay underestimates glycosylated NT-proBNP. In addition, the recently developed high performance dialyzer removes medium-sized molecular solutes such as ß2-microgloburin. We therefore investigated the effects of high performance dialysis on measured levels of glycosylated proBNP, glycosylated NT-proBNP and other BNP-related peptides in end-stage renal disease (ESRD) patients on hemodialysis. METHOD: The relationships between clinical parameters and BNP-related molecule were also investigated. We used our newly developed immunoassay to measure plasma total BNP and proBNP in 105 normal subjects and 36 ESRD patients before and after hemodialysis. Plasma NT-proBNP was measured using Elecsys II after treatment with or without deglycosylating enzymes. We also measured plasma ANP and cGMP using radioimmunoassays. RESULTS: All the measured BNP-related peptides were significantly higher in ESRD patients than healthy subjects. Total BNP (-38.9%), proBNP (-29.7%), glycoNT-proBNP (-45.5%), nonglycoNT-proBNP (-53.4%), ANP (-50.4%) and cGMP (-72.1%) were all significantly reduced after hemodialysis, and the magnitude of the reduction appeared molecular weight- dependent. Both the proBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios were increased after hemodialysis. The former correlated positively with hemodialysis vintage and negatively with systolic blood pressure, while the latter correlated positively with parathyroid hormone levels. CONCLUSION: These results suggest that hemodialysis using super-flux dialyzer removes BNP-related peptides in a nearly molecular weight-dependent manner. The ProBNP/total BNP and glycoNT-proBNP/nonglycoNT-proBNP ratios appear to be influenced by hemodialysis-related parameters in ESRD patients on hemodialysis.

Prospective randomized phase II trial of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma: the THP Monotherapy Study Group Trial.

PURPOSE: We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS: From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence. RESULTS: Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence. CONCLUSION: In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

Objective evaluation of the correction by non-rigid registration of abdominal organ motion in low-dose 4D dynamic contrast-enhanced CT.

We objectively evaluate a straightforward registration method for correcting respiration-induced movement of abdominal organs in CT perfusion studies by measuring the distributions of alignment errors between corresponding landmark pairs. We introduce the concept and describe the advantages of using the surface-normal component of distance between pairs of corresponding landmarks selected so that their surface normal is in one of the three coordinate axis directions, and show that such landmarks can be precisely placed with respect to the surface normal. Using a large population of landmark pairs on a substantial quantity of 4D dynamic contrast-enhanced CT volume data, we quantify the average alignment errors of abdominal organs that remain uncorrected by registration.

Risk factors for overactive bladder in the elderly population: a community-based study with face-to-face interview.

OBJECTIVES: The aim of this study was to measure the prevalence of and risk factors for overactive bladder (OAB) in the elderly. METHODS: A cross-sectional study of elderly subjects was conducted by analyzing data from a community-based Comprehensive Geriatric Assessment on people aged 70 years or older. Trained interviewers performed face-to-face interviews for the assessment of urological symptoms. OAB definition was based on urgency and eight or more episodes of urination per day. The subjects completed a self-administered questionnaire including lifestyle evaluation, Geriatric Depression Scale, Mini-Mental Status Examination and medical history. Brachial-ankle pulse wave velocity was recorded to assess atherosclerotic disease. The analysis included 833 subjects, after the exclusion of 115 subjects who provided insufficient information. RESULTS: Based on the definition of OAB, 153 subjects (18.4%) were identified as having OAB. Univariate analysis showed a significant association between OAB and depressive symptoms. Multivariate analysis showed that the risk of having OAB was significantly higher in subjects with depressive symptoms, current drinkers, and overweight subjects with odds ratios of 2.37 (1.60-3.52, 95% confidence interval), 1.65 (1.04-2.62), and 1.51 (1.02-2.24), respectively. CONCLUSIONS: This is the first report to show an association between OAB and depressive symptoms and alcohol intake in an epidemiological study of elderly people. The reasons for these correlations remain unclear, but should be the foci of future OAB studies.

Impact of nocturia on bone fracture and mortality in older individuals: a Japanese longitudinal cohort study.

PURPOSE: We evaluated the association of nocturia with fracture and death in a large, community based sample of Japanese individuals 70 years old or older. MATERIALS AND METHODS: The baseline in this population based study was determined in 2003 by an extensive health interview with each participant. In this study we followed 784 individuals with a mean ± SD age of 76.0 ± 4.6 years (range 70 to 97). Information on mortality and fracture during the study period was provided by the National Health Insurance system and details on fractures were collected from medical records. We compared the risk of bone fracture and death with or without nocturia in a multivariate Cox proportional hazard model. RESULTS: Nocturia (2 or greater voids per night) was present in 359 of the 784 participants (45.7%). Fracture was observed in 41 cases, including 32 fall related cases. For all fractures and fall related fractures with nocturia the HR was 2.01 (95% CI 1.04-3.87) and 2.20 (95% CI 1.04-4.68, each p = 0.04). Death occurred in 53 cases. The mortality rate in individuals with nocturia was significantly higher than in those without nocturia. For mortality in patients with nocturia the age-gender adjusted HR was 1.91 (95% CI 1.07-3.43, p = 0.03). Even when further adjusted for diabetes, smoking status, history of coronary disease, renal disease and stroke, tranquilizers, hypnotics and diuretics, the positive relationship was unchanged (HR 1.98, 95% CI 1.09-3.59, p = 0.03). CONCLUSIONS: During a 5-year observation period elderly individuals with nocturia were at greater risk for fracture and death than those without nocturia.

Structural basis for regulation of poly-SUMO chain by a SUMO-like domain of Nip45.

Post-translational modification by small ubiquitin-like modifier (SUMO) provides an important regulatory mechanism in diverse cellular processes. Modification of SUMO has been shown to target proteins involved in systems ranging from DNA repair pathways to the ubiquitin-proteasome degradation system by the action of SUMO-targeted ubiquitin ligases (STUbLs). STUbLs recognize target proteins modified with a poly-SUMO chain through their SUMO-interacting motifs (SIMs). STUbLs are also associated with RENi family proteins, which commonly have two SUMO-like domains (SLD1 and SLD2) at their C terminus. We have determined the crystal structures of SLD2 of mouse RENi protein, Nip45, in a free form and in complex with a mouse E2 sumoylation enzyme, Ubc9. While Nip45 SLD2 shares a beta-grasp fold with SUMO, the SIM interaction surface conserved in SUMO paralogues does not exist in SLD2. Biochemical data indicates that neither tandem SLDs or SLD2 of Nip45 bind to either tandem SIMs from either mouse STUbL, RNF4 or to those from SUMO-binding proteins, whose interactions with SUMO have been well characterized. On the other hand, Nip45 SLD2 binds to Ubc9 in an almost identical manner to that of SUMO and thereby inhibits elongation of poly-SUMO chains. This finding highlights a possible role of the RENi proteins in the modulation of Ubc9-mediated poly-SUMO formation.

[Effects of urinary function and erectile function on the use of mecobalamin after nerve sparing radical prostatectomy].

PURPOSE: Mecobalamin has been reported to be useful for peripheral nerve disorder. There have been no previous reports of the effects of mecobalamin on urinary and sexual function after nerve sparing radical prostatectomy. We examined the effects of the use of mecobalamin on urinary and erectile functions after nerve sparing radical prostatectomy. MATERIALS AND METHODS: A total of 54 patients with localized prostatic cancer were prospectively randomized into 2 groups. The 27 patients in group A were treated with nerve sparing prostatectomy and mecobalamin 1,500 microg/day for 6 months. The 27 patients in group B were treated with nerve sparing prostatectomy alone. Urinary function (URF), urinary bother (URB), sexual function (SXF) and sexual bother (SXB) were evaluated using the University of California at Los Angeles Prostate Cancer Index (UCLA-PCI) before surgery, and 3, 6 and 12 months after surgery. RESULTS: There were no significant differences in URF, URB, SXF or SXB between the two groups at any postoperative period. At 3 months after surgery, however, group A tended to have a better URF than group B (85.7 +/- 4.7 (mean +/- standard error) vs. 66.9 +/- 10.2) and URB (85.7 +/- 7.4 vs. 63.9 +/- 11.8) (p = 0.121, p = 0.168). At 12 months after surgery, both groups showed similar URF (86.4 +/- 7.4 vs. 81.8 +/- 4.2) and URB (86.5 +/- 8.3 vs. 84.5 +/- 4.7). Although the two groups had similar recovery phase of SXF, group A tended to report better SXB throughout the postoperative period. CONCLUSION: This study did not demonstrate any significant effect of the use of mecobalamin on the recovery of urinary or sexual function after nerve sparing prostatectomy, although an early recovery effect on urinary function was suggested. A randomized controlled study with a larger population is warranted to fully elucidate the role of mecobalamin in the improvement of functional outcome after radical prostatectomy.

A novel antiangiogenic effect for telomerase-specific virotherapy through host immune system.

Soluble factors in the tumor microenvironment may influence the process of angiogenesis; a process essential for the growth and progression of malignant tumors. In this study, we describe a novel antiangiogenic effect of conditional replication-selective adenovirus through the stimulation of host immune reaction. An attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of E1 genes, could replicate in and cause selective lysis of cancer cells. Mixed lymphocyte-tumor cell culture demonstrated that OBP-301-infected cancer cells stimulated PBMC to produce IFN-gamma into the supernatants. When the supernatants were subjected to the assay of in vitro angiogenesis, the tube formation of HUVECs was inhibited more efficiently than recombinant IFN-gamma. Moreover, in vivo angiogenic assay using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice showed that tumor cell-induced neovascularization was markedly reduced when the chambers contained the mixed lymphocyte-tumor cell culture supernatants. The growth of s.c. murine colon tumors in syngenic mice was significantly inhibited due to the reduced vascularity by intratumoral injection of OBP-301. The antitumor as well as antiangiogenic effects, however, were less apparent in SCID mice due to the lack of host immune responses. Our data suggest that OBP-301 seems to have antiangiogenic properties through the stimulation of host immune cells to produce endogenous antiangiogenic factors such as IFN-gamma.

Spontaneous regression of pulmonary metastases from testicular embryonal carcinoma.

A 22-year-old man was referred to our hospital for a lung tumor on a chest X-ray examination. Computed tomography of the chest revealed multiple coin lesions. Magnetic resonance imaging of the left testis showed an 8-mm tumor that was hard and palpable. Testicular tumor with lung metastasis was diagnosed and orchiectomy was performed. The histopathological diagnosis was embryonal carcinoma with infiltration of histiocytes. Four days after the operation, a chest X-ray showed a remarkable regression of the lung tumors. Chemotherapy was not performed because the metastatic lesions continued to regress spontaneously. Six months later, no tumor was observed on computed tomography images of the lungs.

Potentiation of potassium currents by beta-adrenoceptor agonists in human urinary bladder smooth muscle cells: a possible electrical mechanism of relaxation.

We examined the effects of beta-adrenoceptor agonists on the membrane currents of smooth muscle cells from the human urinary bladder using a whole-cell patch clamp to investigate the involvement of Ca(2+)-activated K(+) (K(Ca)) channels in relaxation by beta-adrenergic agonists. With 0.05 mmol/l EGTA in the patch pipette, depolarizing pulses evoked outward rectifying currents. Isoproterenol (1 micromol/l) significantly increased the membrane currents by 75% at +80 mV with 0.05 mmol/l EGTA pipette solution. BRL 37344 (1 micromol/l) significantly increased the membrane currents by 44% at +80 mV. Iberiotoxin (100 nmol/l) significantly decreased the membrane currents by 60% at +80 mV. In the presence of iberiotoxin, the potentiation of the outward currents by isoproterenol was greatly suppressed and, in the presence of iberiotoxin and apamin (1 micromol/l), the potentiation by isoproterenol was totally abolished. On the other hand, with 5 mmol/l EGTA pipette solution, depolarizing pulses evoked smaller outward currents. Isoproterenol (1 micromol/l) did not change the membrane currents with 5 mmol/l EGTA pipette solution. The real-time PCR analysis revealed the expression of beta(2)-adrenoceptors in the cells. These results suggest that Ca(2+)-activated and iberiotoxin- and apamin-sensitive currents via both large-conductance and small-conductance K(Ca) channels could be increased by stimulation of beta(2)-adrenoceptors.

[Pulmonary and lymph node metastases of renal cell carcinoma which completely responded to oral administration of UFT--a case report].

In April 2003, a 59-year-old woman suffering from renal cell carcinoma (RCC) underwent radical nephrectomy (Stage I). In October 2004, bilateral lower lobe lung tumors were resected with thoracoscopic assistance. Histologically, resected specimens were diagnosed as metastases from RCC. However, 2 months later,lung and abdominal lymph node metastases were detected by CT. Chemotherapy with interferon-alpha (IFN-alpha) 6,000,000 units every day was performed, but was discontinued after 3 months due to fatigue and depression. Because the tumor marker (IAP) level and the size of the metastatic tumors increased, second-line chemotherapy with oral administration of tegafur/uracil (UFT-E 600 mg/day) was started. Six months after UFT administration, there was a significant decrease of tumor markers and the metastatic tumors were disappeared, therefore we were judged as complete response (CR). No grade 3 or more severs adverse reactions have been observed. Some cases may be effectively treated by UFT after treatment failure of IFN-alpha therapy. This UFT therapy is simple and possible to continue safely on an outpatient chemotherapy while maintaining quality of life.