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Phosphate binders are used for the treatment of hyperphosphatemia in hemodialysis patients with chronic kidney disease. Sevelamer, a phosphate-binding polymer, has been reported to bind bile acids or fatty acids and thereby decrease its phosphate-binding capacity. The novel phosphate binder TRK-390 is a poly (allylamine) polymer that has been shown to have enhanced phosphate selectivity, with low bile-acid-binding. In this study we evaluated the effect of fatty acids on the phosphate-binding capacity of TRK-390. In the absence of fatty acids and bile acids, the phosphate-binding capacity of TRK-390 was similar to that of sevelamer. In the presence of fatty acids and bile acids, the phosphate-binding capacity of TRK-390 was reduced to 83%; in contrast, that of sevelamer was reduced to 35%. TRK-390 and sevelamer showed a similar effect in lowering urinary phosphate excretion in normal rats fed a normal diet. However, urinary phosphate excretion of rats treated with TRK-390 was reduced by about one half of that obtained with sevelamer, when given with a high-fat diet that had a fat content similar to the diet of hemodialysis patients. TRK-390 was superior in terms of phosphate selectivity in the presence of fatty acids and bile acids in vitro, and the phosphate-binding capacity of TRK-390 in vivo was shown to be less affected by fat in comparison with that of sevelamer. Thus, TRK-390 is expected to be useful as a novel highly selective phosphate binder.

BACKGROUND: There is considerable interest in the pleiotropic pharmacological action of sarpogrelate hydrochloride, a novel selective serotonin 2A receptor antagonist. In the present study the persistent insulin-sensitizing effects of sarpogrelate were investigated in non-diabetic and non-medicated diabetic patients with peripheral artery disease (PAD). METHODS AND RESULTS: Indices of insulin resistance (IR) (fasting immunoreactive insulin (IRI) and calculated homeostasis model assessment (HOMA-R)) and adiponectin were measured before and after 2 weeks of sarpogrelate administration (300 mg/day) in 24 patients (19 men, 76+/-9 years) with PAD. Sixteen of the 24 patients were examined after 3 months of treatment for assessment of the chronic effect of sarpogrelate on IR. After 2 weeks of treatment, significant decreases in fasting IRI (p=0.03) and HOMA-R (p=0.024), but not in adiponectin, were observed. After 3 months of treatment, significant decreases in fasting IRI (16.0+/-10.3 vs 9.2+/-2.0 microU/ml, p=0.03) and HOMA-R (4.30+/-2.83 vs 2.40+/-0.74, p=0.025) were maintained. Furthermore, adiponectin was significantly increased (8.11+/-4.13 vs 9.64+/-4.37 microg/ml, p=0.027). All of the examined HOMA-R had a significant correlation with all of the examined adiponectin (p

Background: We evaluated the efficacy and safety of transurethral needle ablation (TUNATM) of the prostate for treatment of symptomatic benign prostatic hyperplasia (BPH) as one institute participating in a Japanese clinical trial. Methods: Thirty-three patients with symptomatic BPH were treated with the TUNATM procedure in our institute. The international prostate symptom score (IPSS), quality of life (QOL) score, residual urine volume (RV), prostate volume (PV) and peak urinary flow rates (Qmax) were measured and complications were assessed. Results: We followed and evaluated 30 of the 33 cases. At 12 months there were significant improvements in the IPSS (20.7 to 11.2, P < 0.0001), QOL score (4.9 to 2.1, P < 0.0001), RV (46.6 to 22.6 mL, P < 0.01), PV (37.8 to 30.0 mL3, P < 0.002) and Qmax (8.00 to 11.0 mL/s, P < 0.002). There were no serious complications. Conclusion: This trial shows that the TUNATM procedure is a safe and efficacious treatment for symptomatic BPH.

OBJECTIVES Combined androgen blockade (CAB) uning LH-RH agonist and flutamide has been performed as neoadjuvant therapy for T 2, 3 prostate cancers (CaP). The histological effects of neoadjuvant CAB therapy and influential factors were investigated. METHODS Materials were 20 CaP cases which were underwent radical prostatectomy (RP) after neoadjuvant CAB therapy. All cases were diagnosed by echo-guided sextant needle biopsies. RP was performed after serum PSA was decreased to undetectable level. Histological effect was evaluated by general rule for clinical and pathological studies on prostate cancer (Japanese Urological Association). All cases were divided 2 groups by histological effects as follows: Group A (poor effect group): G 0 and G 1, Group B (good effect group): G 2 and G 3. Immunostaining of p 53 (mutant type), bcl-2 and Chromogranin A (ChA) were performed for both pretreatment needle biopsy and RP specimen. In addition, pretreatment serum PSA and Gleason grade were also investigated. RESULTS Down grading were found in 30%. Down staging were found in 35% (7 cases). All 7 cases were negative surgical margins and 5 of 7 were clinical T 3. Negative bcl-2 of biopsy specimen was correlation with down grading (p = 0.008). In the histopathological evaluation, G 0 was 1, G 1 were 10, G 2 were 6 and G 3 were 3 cases. Gleason 4 or 5 elements of biopsy were found in 9/11 cases in Group A but only 3/9 cases in Group B (p = 0.027). The bcl-2 positive cells of biopsy were found in 8/11 cases in Group A but only 1/9 cases in Group B (p = 0.006). The p 53 and/or bcl-2 positive cells of biopsy were found in 10/11 cases in Group A but only 3/9 cases in Group B (p = 0.007). Serum PSA and ChA were not correlation with histological effect of neoadjuvant CAB therapy. But, in 3 cases, ChA positive cell appeared after neoadjuvant therapy. CONCLUSIONS We could not expect more than 50% cases to show the down grading and down staging. But, in T 3 case, surgical failure could be decrease. We could expect prostate cancer cases without positive bcl-2 cells, p 53 over expression and Gleason 4 x 5 to reveal the good histological effects of neoadjuvant CAB therapy.

A 47-year-old woman was admitted when a mass in the urinary bladder was pointed out on ultrasound follow-up after hysterectomy for uterine myoma. Cystoscopy, ultrasonography, CT scan and MRI suggested a tumor in the muscle layers of the urinary bladder. Since the possibility of malignancy could not be ruled out, partial cystectomy was performed. The tumor was diagnosed as endosalpingiosis, a subclassification of mullerianosis histologically. The concept of endosalpingiosis has appeared recently and only 3 cases have been reported none of who had severe symptoms. Our case is the forth in the world. One of these cases had been treated with hormonal therapy as endometriosis, with no effect. Therefore, surgery is recommended as the first treatment of choice.

In this study, we present the vibration analysis procedure of a hydrostatic gas bearing spindle considering the stiffness and damping of a gas film and the effect of elastic deformation of the components of a rotor. An equation of motion for the elastic vibration of the rotor is formulated using the finite element method and then combined with the rigid-body equation of motion of the housing and the gas film stiffness and damping calculated from the frequency domain analysis of the perturbed Reynolds equation. Since the gas film stiffness and damping are functions of frequency and mode shape, the natural frequency and the damping ratio of each vibration mode are calculated iteratively until both the eigenvalue analysis and gas film analysis are satisfied. The calculated natural frequencies of the gas bearing spindle are found to be in good agreement with the experimental ones. The calculated damping ratios qualitatively agree with the experimental ones with quantitative discrepancy of 30% for the same mode.

We evaluated 59 patients with voiding dysfunction after abdominal radical hysterectomy for uterine cancer. Of 59 patients, 45 underwent the surgery alone, and the other 14 underwent surgery and postoperative radiotherapy. Irradiation (mean dose, 60 Gy) was performed in bilateral commoni iliac regions excluding the bladder. In principle, the indwelling urethral catheter was removed 4 days after operation. All patients were followed up at the gynecological department until the onset of the voiding dysfunction. The mean interval between operation and the onset of voiding dysfunction was significantly longer (P < 0.01) in the group treated by surgery alone (7.9 years) than in the group treated by surgery in combination with radiotherapy (3.8 years). Voiding dysfunction developed earlier as the age at the time of operation was higher. No differences were observed in the volume of residual urine, the detrusor function, or the incidence of urinary tract infection between the two groups. These results suggest that aged patients develop voiding dysfunction earlier after radical hysterectomy than young patients, and postoperative radiotherapy shortens the interval between operation and the onset of postoperative voiding dysfunction.

A case of primary malignant lymphoma of the bladder is reported. A 70-year-old woman was admitted to our clinic with the chief complaint of intermittent gross hematuria on March 31, 1992. Examination of cystoscopy, IVP, ultrasonography and CT scan suggested a non-papillary invasive bladder tumor. Pathological examination of transurethral biopsy revealed malignant lymphoma, B cell type. After 5 courses of intraarterial COMPA (CDDP, VCR, MTX, PEP, ADR) chemotherapy, she have been in complete remission. Intraarterial COMPA chemotherapy might be effective and useful for primary malignant lymphoma of the urinary bladder.

Background: Impaired left ventricular (LV) function is shown by strain rate (SR) imaging in patients with diabetes mellitus (DM). Left atrium (LA) function in patients with DM, however, has not been assessed by this method and the effect of hypertension (HT) on LV and LA functions in diabetic patients has not been fully studied. The aim of this study was to quantitatively assess LA function in diabetic patients with and without HT in combination with LV function. Methods: Conventional echocardiographic and SR imaging studies were performed in 55 subjects with normal systolic LV function (LV ejection fraction of 55% or more) and no evidence of coronary artery disease: 17 with DM (DM group), 22 who have both DM and HT (DM+HT group), and 16 age-matched controls. SR imaging was performed from three apical views, and peak SR was measured at 12 LV segments and 5 LA segments. Mean peak systolic SR (LVs and LAs, respectively), early diastolic SR (LVe and LAe, respectively) and late diastolic SR (LVa and LAa, respectively) were calculated by averaging data in each LV and LA segment. Results: Despite no significant differences in age, LV ejection fraction and E/A ratio among the three groups, systolic blood pressure, LA dimension and LV mass index in the DM+HT group were significantly larger than those in the controls. The DM group had reduced systolic and diastolic LV functions and impaired LA reservoir and conduit functions compared with those in the controls, as shown by lower LVs (P < 0.05), LVe (P < 0.01), LAs (P < 0.01), and LAe (P < 0.05). The DM+HT group had reduced LVs (P < 0.01), LVe (P < 0.01), LAs (P < 0.01) and LAe (P < 0.01) compared with those in the controls. The DM+HT group had significantly lower LVe (P < 0.05) and LAe (P < 0.05) than did the DM group. Conclusions: SR imaging can detect impairment of LA reservoir and conduit functions as well as LV systolic and diastolic dysfunctions in patients with DM, even in the absence of LV hypertrophy and LA dilatation. Coexisting HT augments the impairment of LV diastolic and LA conduit functions in diabetic patients.

The relative risk for a second primary cancer after the diagnosis of prostate cancer and the prognostic impact of the association of multiple primary malignant neoplasms (MPMNs) in patients with prostate cancer were analyzed in a retrospective study. The development of MPMNs was examined in 312 consecutive patients who had been diagnosed with prostate cancer between 1966 and 1992. The population-based cancer incidence rates in Japan were utilized to calculate the expected number of MPMNs. Of the 312 patients, 60 fulfilled the diagnosis of MPMNs. In 13 men, prostate cancer and other malignancies were diagnosed simultaneously. In 35 of the 312 patients, prostate cancer was the second or third cancer diagnosis. In the remaining 287 patients, prostate cancer developed initially. Of the 287 patients, 12 developed a second primary malignancy compared with 17 expected (relative risk 0.71, 95% confidence interval 0.45-1.4). No single anatomic site showed a significantly increased risk above that expected either. The overall survival of patients with prostate cancer was not reduced by the association with MPMNs. This may be explained by the fact that the stage of the prostate cancer was lower in patients with MPMNs than in patients without MPMNs.

Of 130 cases with renal cell carcinoma treated at Cancer Institute Hospital from January, 1981 to December, 1992, 14 (10.6%) developed brain metastasis, 12 of whom had had preceding pulmonary metastasis. Interval between the initial treatment of the primary lesion (nephrectomy in 13, embolization in 1) and the diagnosis of brain metastasis ranged 0 to 57 months with a median of 11 months. Twelve patients had clinical symptoms such as headache, vomiting, paralysis or disturbance of consciousness. Eleven patients were treated with external beam irradiation (30-60 Gy linear accelerator). Only 3 (30%) of 10 patients with measurable lesion on CT scan achieved PR but 6 (66.7%) of 9 had symptomatic improvement. Especially, chronic intracranial hypertension such as headache and vomiting disappeared in 5 (83.3%) of 6. Average survival period and one year survival after the diagnosis of brain metastasis were 5 months and 14.3%. Although most of the patients with brain metastasis died of the progression of other organ metastasis, radiation therapy for brain metastasis was useful to palliate the agonizing symptoms.

We have developed a new combination intravenous chemotherapy regimen called COMPA (IV-COMPA). The clinical value of IV-COMPA chemotherapy was evaluated based on the results of 24 patients with urothelial cancers. From October 1989 through October 1993, a total of 24 patients (20 males and 4 females) received IV-COMPA chemotherapy at Tokyo Medical College Hospital and Tokyo Medical College Hachioji Medical Center. All patients had advanced transitional cell carcinoma or adenocarcinoma of the urothelial tract (renal pelvis, ureter or bladder). One course of IV-COMPA was delivered at 2-week intervals and consisted of 30 mg/m2 CDDP on day 4 and 5, 0.6 mg/m2 VCR (Oncovin) on day 1 and 2, 5 mg/m2 MTX on day 2 and 3, 5 mg/m2 PEP on day 1, 2 and 3, 20 mg/m2 ADM on day 4. A few patients received the same regimen without peplomycin called IV-COMA to avoid pulmonary fibrosis. Fifteen patients with surgically confirmed invasive carcinoma were defined by at least 1 of the following criteria: multiple tumors or size greater than 5 cm, grade 3, stage P3 or P4, pN+, pR1, pL1, pV1, or secondary carcinoma in situ. These patients were treated with 2 or 3 corpses of postoperative IV-COMPA chemotherapy to improve prognosis. In this group, 14 of 15 (93%) are alive at a median follow-up of 22 months (range, 8-57 months) and actuarial survival rates of 1 and 3 years were 100%, 90.9%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

In a 26-year-old male with 17 alpha-hydroxylase deficiency, endocrinological examinations were performed not only after, but also before the onset of clinical signs and symptoms. In addition, the pathophysiological role of the renal kallikrein-kinin system was investigated in this patient. In spite of the fact that this disease is congenital, in the mechanism of its onset, this patient had a period of endocrinological normality before onset; that is, 9 months before onset, both ACTH and cortisol were within the normal range, although the former would be significantly higher and the latter significantly lower than normal values after the onset. In this case, both urinary kallikrein and kininase excretions abnormally increased and then returned to normal after dexamethasone treatment.

In order to clarify the role of dopamine on the pathophysiology of essential hypertension, mean arterial pressure (MAP), heart rate (HR), urine volume (UV), urinary sodium excretion (UNaV), endogenous creatinine clearance (Ccr), fractional excretions of sodium (FENa), inorganic phosphorus (FEP) and potassium (FEK), plasma renin activity (PRA), plasma aldosterone concentration (PAC) and plasma noradrenaline concentration (PNA) were measured before and after intravenous infusion of dopamine (3 micrograms/kg/min, 60 min) in normotensive (NT) and essential hypertensive subjects (EHT). Following dopamine infusion, a significant decrease of MAP and an increase of HR were observed in EHT but not in NT. UV, UNaV, Ccr, FENa, FEP and FEK increased significantly in both NT and EHT, and changes in these except for Ccr were significantly greater in EHT than in NT. In EHT, following dopamine infusion, PNA was clearly elevated, but no remarkable change was found in PRA and PAC. A significantly positive correlation was found between delta UNaV and delta FENa or delta FEP, and between delta FENa and delta FEP, while no significant relation was observed between delta UNaV and delta Ccr, delta MAP or MAP before dopamine infusion. A significant inverse correlation between supine PRA before dopamine infusion and delta FENa or delta FEP and a positive correlation between age and delta FENa or delta FEP were also observed in these patients. The changes in UNaV positively correlated with delta FENa and delta FEP in both low renin (group L) and normal renin EHT (group N) and with delta Ccr i group N but not in group L. The mean values of delta FENa, delta FEP and delta FEK were significantly higher in group L as compared with those in age-matched group N. These results suggest that, since the enhanced response to infused dopamine may reflect reduced dopaminergic activity, attenuation of renal dopaminergic activity might exist and be involved through a distribution of water-sodium metabolism, at least in part, in the pathophysiological mechanism in EHT, particularly in group L.