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Y Tsubakihara

Publications and source records attributed to Y Tsubakihara.

34 records · Page 2Linked to original sources

[Pharmacokinetic study of ofloxacin using saliva concentration in chronic renal failure].

We evaluated saliva concentration as a parameter of therapeutic drug monitoring (TDM) of Ofloxacin (OFLX) in patients with severe renal failure (CRF). Saliva OFLX concentration correlated closely with serum OFLX concentration as shown in healthy subjects, although it was significantly lower (about three-quarters), indicating that OFLX had less penetration into saliva in patients with renal failure. Saliva concentration was almost equal to serum concentration during hemodialysis, which might have been due to the constant dialysis of OFLX. In conclusion, saliva concentration was useful for TDM of OFLX in patients with CRF, as it is in healthy subjects.

Adolescent↗

[Circadian blood pressure pattern in the patients with chronic glomerulonephritis].

Circadian blood pressure pattern in the patients with chronic glomerulonephritis was studied by ambulatory 24-hour blood pressure monitoring (ABPM). Subjects were 32 patients and were divided into three groups with various renal function; Ccr of 10 patients were normal (Ccr > or = 70 ml/min), 10 patients 30 < or = Ccr < 70 ml/min and the Ccr were below 30 ml/min in the other 12 patients. Blood pressure levels were significantly higher in reduced Ccr groups as compared with normal Ccr cases. The blood pressure gradient between day-time (7:00-19:00) and sleeping time (1:00-5:00) significantly decreased in the patients with renal impairment as compared with normal Ccr cases. And it positively correlated with Ccr (r = 0.51, p < 0.01). These results indicate that the patients with reduced renal function in chronic glomerulonephritis show abnormal circadian blood pressure pattern and nocturnal hypertension, which may require novel modification of antihypertensive treatment.

Blood Pressure↗

[Predictability of creatinine clearance from serum creatinine in chronic glomerulonephritis].

We evaluated the formulas of urine-free prediction of creatinine clearance (CCr) for clinical use in the patients with chronic glomerulonephritis (CGN). Subjects were 246 patients with CGN diagnosed by renal biopsy with range from normal renal function to end stage renal failure. CCr were measured exactly with urine collections more than 2 times and compared with the values calculated using four urine-free mathematical formulas of Cockcroft et al, Mawer et al, Konishi et al, and Tozune et al. Strong, statistically significant correlations were observed between CCr estimated with each prediction method and measured CCr (r > or = 0.946). However, the latter two formulas tended to overestimate the values. Predicted errors more than 20% of the formula of Cockcroft et al, were the least. And their formula was the easiest for clinical use because of the simplicity for learning by heart. We conclude that these four formulas can be used with reasonable accuracy in the patients with CGN from normal renal function to end stage renal failure, and the formula of Cockcroft et al, is the most recommendable for clinical use.

Adolescent↗

[Effect of recombinant human erythropoietin on renal function in predialysis patients].

To assess the effect of recombinant human erythropoietin (EPO) on renal function, the slopes of the regression lines of the reciprocal of serum Cr versus month (l/Cr) were studied in 8 pre-dialysis outpatients (2.9 ml/min. less than Ccr less than 17.0, 21.4% less than Ht less than 27.9) who had been followed for a period of 19 to 94 months. EPO was initially given 3000-6000 U (133 +/- 31 U/Kg/week) once weekly by the intravenous route and was later switched to the dose to achieve a Ht level of 30-35%. Mean Ht increased from 23.6 +/- 0.9 to 33.2 +/- 1.1%, and quality of life and exercise capacity were significantly improved in all patients. The mean slopes of l/Cr after EPO (-0.0050 +/- 0.0020) were not significantly different from the values before EPO (-0.0064 +/- 0.0010). The slopes of l/Cr were significantly decreased by EPO therapy in three patients observed for more than 17 months, however in one patient, it increased significantly during EPO treatment. There were no significant differences in the other 4 patients. The renal function at the initiation of EPO in a patient with increase slope of l/Cr had been the worst, and Ht was mildly increased from 21.4% to 24.1% and the blood pressure did not change significantly. The good effect on renal function observed in 3 patients may, in part, be due to better control of blood pressure and physical condition (including cardiac and immunological function) by the more close follow-up of the patients and the improvement of anemia during the period of EPO therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Affinity purification of kallikrein and elastase from hog pancrease powder.

The present report describes a method that is efficient for simultaneous isolation of kallikrein and elastase from hog pancrease powder. Both enzymes were separated by successive column chromatography on CM-cellulofine and p-aminobenzamidine-Sepharose 4B. Kallikrein was further purified by column chromatography on DEAE-Sephadex and elastase was purified by repeated gel chromatography on Sephadex G-75. The kallikrein obtained was composed of two components, which were separable by sodium dodecyl sulphate polyacrylamide gel electrophoresis, and the elastase had one component. The activity yields of kallikrein and elastase were 49 and 38%, respectively.

Amino Acids↗

Tissue and blood cell concentration of methylguanidine in rats and patients with chronic renal failure.

Methylguanidine concentration in blood cell of nondialysed patients with chronic renal failure was quantitatively determined by the method of the present authors. We also determined tissue methylguanidine concentrations in the liver, blood cell, kidney, colon, muscle and brain of uremic rat experimentally produced by Platt's method. Methylguanidine concentrations in blood cell and tissues except the brain of the uremic rats and in blood cell of the uremic patients were 5--7 times higher than those in their serums. An increased methylguanidine concentration in the liver of the uremic rat receiving 40% protein diet was observed. These results imply that methylguanidine acts as one of the important uremic toxins in the intracellular space except for the brain, and suggest that the liver specifically affects the formation of methylguanidine.

Animals↗

Effect of low protein diet and surplus of essential amino acids on the serum concentration and the urinary excretion of methylguanidine and guanidinosuccinic acid in chronic renal failure.

20 patients with moderate renal failure (serum creatinine 4.5--12.0 mg/dl) and some uremic symptoms on a diet ad libitum were treated with a high caloric diet containing 0.5--0.7 g/kg/day protein, supplemented with eight essential amino acids and histidine in the form of solution and/or granules. During the treatment uremic symptoms subsided or diminished without the signs of malnutrition, SUN and the ratio SUN/S-creatinine fell and the nitrogen balance and the ratio N-balance/intake N improved. The serum concentration and the urinary excretion of MG and GSA of the 12 patients were determined by Stein's method using the modified Sakaguchi reaction. In all patients, the serum concentration and the urinary excretion of MG and GSA diminished remarkably during the treatment with a low protein diet alone and furthermore with a low protein diet and essential amino acid supply. We concluded that conservative treatment -- low nitrogen diet supplemented with sufficient calories and essential amino acids -- improved the nutritional state of uremic subjects, and decreased the metabolic production of MG and GSA. The results show that the supplementation of essential amino acids to uremic patients may be a useful treatment.

Adult↗

Effect of arginine or creatinine administration on the urinary excretion of methylguanidine.

The metabolic pathway of methylguanidine (MG) is mainly speculated from the change in urinary excretion of MG in the arginine (Arg)-injected normal rat, the creatinine (Cr)-injected normal rat, and the Arg-injected uremic rat. 15N-Arg was ingested to 2 uremic patients. Arg administration resulted in marked increase in urinary MG excretion both in the uremic rat and patient, but not in the normal rat. In the first phase of the 15N-Arg ingestion experiment, a rapid rise of 15N atom percent excess of urinary MG was observed in the uremic patient. In the second phase of this study, after 24 h of 15N-Arg ingestion, the 15N atom percent excess of urinary Cr and that of MG closely paralleled. These findings imply that there might be two metabolic origins of MG: one is a formation of MG from Arg itself or an Arg metabolite other than Cr, the other a pathway producing MG via Cr. The former is compatible with the hypothesis by Cohen.

Animals↗

Effects of low-dose simvastatin therapy on serum lipid levels in patients with moderate hypercholesterolemia: a 12-month study. The Simvastatin Study Group.

The aim of this study was to investigate the safety and long-term effects on serum lipid levels of low-dose simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, in Japanese patients with moderate primary hypercholesterolemia. We assigned 201 patients (68 men and 133 women; mean +/- SD age, 61.3 +/- 10.2 years) with serum total cholesterol levels > or = 220 mg/dL to receive simvastatin 5 mg each evening; the treatment period was 1 year. Serum total cholesterol, triglycerides, and low-density lipoprotein (LDL) cholesterol levels decreased significantly in response to simvastatin therapy, and the changes were maintained throughout the treatment period. Mean total cholesterol decreased from 269.9 +/- 35.4 mg/dL to 215.2 +/- 34.5 mg/dL (20.3%), triglycerides decreased from 183.0 +/- 110.2 mg/dL to 155.5 +/- 88.5 mg/dL (15.0%), and LDL cholesterol decreased from 180.0 +/- 33.1 mg/dL to 130.1 +/- 35.1 mg/dL (27.7%). Total cholesterol, triglycerides, and LDL cholesterol tended to decline when the pretreatment values were higher; the critical values and the bidirectional changes of the serum lipid levels were 188.1, 109.5, and 91.6 mg/dL, respectively. Although the serum level of high-density lipoprotein cholesterol did not change significantly, it tended to increase more when the pretreatment values were lower; the "critical value" was 70 mg/dL. Nine patients experienced mild adverse events, but none discontinued simvastatin during the 12-month treatment period. We found that low-dose simvastatin therapy is effective in achieving long-term decreases in serum lipid levels and is well tolerated by patients with moderate hypercholesterolemia. Simvastatin therapy may result in normalization of serum lipid levels.

Adult↗

Pharmacokinetics of ofloxacin in severe chronic renal failure.

The pharmacokinetics of ofloxacin were studied in patients with severe renal impairment. In five healthy subjects and nine patients with chronic renal failure (CRF) (creatinine clearance [CCR] less than 20 ml/min) receiving 100 mg of ofloxacin orally in the fasted state, the serum concentration was measured over the subsequent 48 hours. Intracorporeal dynamics were examined, employing a one-compartment open model. Ofloxacin levels were measured using the paper disk method. The half-life of ofloxacin was markedly prolonged, to 23.1 +/- 7.0 hr in the CRF group versus 2.9 +/- 0.5 hr for healthy subjects. In the CRF group, the maximum concentration and area under the curve were greater than in healthy subjects. There were no significant differences in volume of distribution between the two groups. The renal clearance of ofloxacin decreased from 261.0 +/- 46.6 ml/min in healthy subjects to 8.0 +/- 4.7 ml/min in the CRF group and correlated significantly with CCR in the CRF group (r = .88, P less than 0.01). There were no significant differences in nonrenal clearance between the two groups. The 24-hour renal excretion of ofloxacin averaged 91.9 +/- 5.4% and 14.1 +/- 5.5% of the dose in the healthy and CRF groups, respectively. In three hemodialysis patients on the regular hollow-fiber dialyser, the dialysance of ofloxacin was about 50% that of creatinine. Based on these findings, a reduction in the dose of ofloxacin is necessary in patients with CRF. In the hemodialyzed patients, its high dialyzability should be considered when deciding dose regimens.

Creatinine↗