Optimum dosage of pergolide in patients with Parkinson's disease]

For the purpose of determining the optimal dose, pergolide was administered to patients with Parkinson's disease using a dose-escalation protocol up to the maximum dosage permissible in Japan. The study was completed in 16 subjects with Parkinson's disease. Prior to the start of the dose-escalation study, the daily dose of pergolide was 500 microg in 6 patients and 750 microg in 10 patients. The daily dose was raised by 250 microg at 4-week intervals up to the approved maximum dose of 1,250 microg/day, which was used as the final level. Just before the start of study and after administration for 4 weeks at each dose level, UPDRS-III and PDQ-39 assessments were performed. The mean UPDRS-III score was 28.6 +/- 7.9 before the start of the study and 17.3 +/- 8.3 after the end, indicating an improvement (improvement rate, 39.3%; p < 0.01). The mean PDQ-39 score was 45.2 +/- 21.8 before the start and 37.3 +/- 17.8 after the end, indicating an improvement (improvement rate, 17.5%; p < 0.05). Clinical conditions including their QOL improved significantly after dose-escalation up to the 1,250 microg.     

Surgical treatment for carcinoma of the papilla of vater

Eighty of 89 patients who underwent radical resection (resectability 89.9%) for carcinoma of the papilla of Vater between 1976 and 1992 were retrospectively reviewed. Seventy-three patients underwent pancreaticoduodenectomy (PD) and 7 underwent pylorus-preserving pancreaticoduodenectomy (PPPD). The postoperative mortality rate was only 3.8% (3 patients). The 3- and 5-year survival rates were 63.6% and 57.4%, respectively. Important factors influencing long-term survival were Stage (clinical stage = Stage), microscopic lymph node metastasis (n), duodenal wall invasion (d), vascular invasion (v), and the epithelium of origin. Early carcinoma of the papilla of Vater is defined as tumor in which invasion is limited within the papilla of Vater; in particular, carcinomatous invasion is within the muscle of Oddi (d₀) with n₀. PD and/or PPPD with radical lymph node dissection should be performed for carcinoma of the papilla of Vater, as these procedures can be performed with low morbidity and mortality.     

Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

Primary Adenocarcinoma in the Urethrorectal Fistula

A 60-year-old Japanese man was hospitalized because of urinary leakage from the anus on October 3, 1994. Retrograde urethrography detected a fistula between the bulbous urethra and the rectum. Urethrocystoscopy revealed a tumor on the urethrorectal fistula. Tumor biopsy showed a well differentiated adenocarcinoma. Cystourethrectomy with fistulectomy, and ileal conduit urinary diversion were performed. Pathological examination revealed primary adenocarcinoma in the fistula with invasion to the prostatic urethra and bladder wall. The patient showed no evidence of a recurrence as of August, 1996.     

Leukocytosis and low serum IgA in workers exposed to the epoxy compound,t-methyl-3-phenylglycidate

Summary Forty-nine out of 54 male workers engaged in the production of an epoxy compound, t-methyl-3-phenylglycidate, showed skin symptoms in varing degrees that may be due to the skin-irritative effect of the compound. The exposed workers were also shown to have subjective symptoms which may be related to the irritative property of the compound on surface tissue. Laboratory examinations on the blood obtained from the exposed workers showed significantly higher values of leukocyte concentration as compared with the non-exposed controls. This was chiefly caused by the increase of neutrophilic granulocytes and T-cell lymphocytes. Serum IgA levels of the exposed workers were shown to be significantly lower than those of the control group. Hemoglobin concentration, hematocrit value and red cell count of the exposed workers remained at the same level as those of the control subjects. Liver or kidney damage was not found in biochemical analyses on the sera of exposed workers.     

Effects of dilevalol,an R,R-isomer of labetalol,on blood pressure and renal function in patients with mild-to-moderate essential hypertension

Summary The effects of oral dilevalol (an R, R-isomer of labetalol), a new -adrenoceptor blocker with ₂-receptor stimulating and -recepter blocking properties on blood pressure, renal function, plasma renin activity (PRA) and plasma aldosterone have been studied in 15 patients with mild-to-moderate essential hypertension treated with it for 6 weeks.Two patients with apparent treatment failure and one patient who developed muscle pain and cramps, and had an elevated creatine phosphokinase level, were excluded from the study.Dilevalol monotherapy 100 mg once daily for 6 weeks significantly lowered both the systolic and diastolic blood pressure compared to placebo. Total renal vascular resistance was significantly reduced, and RBF and GFR remained unchanged. Dilevalol significantly decreased PRA.The results suggest that prolonged daily treatment with dilevalol preserves renal function and produces a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. The ancillary pharmacological properties of dilevalol rather than PRA suppression may be relevant to its renal effects.     

Genetically determined N-acetylation and oxidation capacities in Japanese patients with non-occupational urinary bladder cancer

Summary Genetically determined polymorphisms of N-acetylation and oxidative capacity have been studied using dapsone and metoprolol in 51 Japanese patients with spontaneous bladder cancer and 203 healthy control subjects.The results for N-acetylation pharmacogenetics were against the initial expectation that there would be a preponderance of slow acetylators in the cancer group, as 3 such patients (5.9%) were found as compared to 13 (6.4%) in the healthy group. There was no poor metabolizer (PM) of metoprolol in the cancer group, whereas in the healthy group one (0.5%) was a PM. There were no significant differences between the groups in the frequency of slow acetylator and poor oxidiser phenotypes, or in the frequency distribution profiles of acetylation (monoacetyldapsone/dapsone) and oxidative metabolic ratio (log metoprolol/-hydroxymetoprolol).The results indicate that neither N-acetylation nor the debrisoquine/sparteine-type oxidative phenotype and/or capacity represent a genetic predisposition to spontaneous bladder carcinogenesis in Japanese patients. In the normal Japanese population there is a great predominance of rapid acetylators and extensive oxidisers.