Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m²), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m²), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m²), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m²). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe.     

Effect of a Device-Free Compressed Shell Fixation Method on Hepatic Respiratory Movement: Analysis for Respiratory Amplitude of the Liver and Internal Motions of a Fiducial Marker

Purpose

Suppression of respiratory movement of the liver would be desirable for high-precision radiation therapy for liver tumors. We aimed to investigate the effect of our original device-free compressed shell fixation method and breathing instruction on suppression of respiratory movement. The characteristics of liver motion based on the movement of a fiducial marker were also analyzed.

Case of autoimmune neutropenia with severe marginal periodontitis

Early onset periodontitis is rarely seen in infants, though often leads to an acute and serious clinical course when encountered in such patients. Autoimmune neutropenia presents systemic and dental symptoms, as depressed resistance to bacterial infection is caused by a disorder that reduces the number of neutrophils. This disease can result in not only gingival inflammation but also destruction of periodontal tissues, such as attachment loss, alveolar bone absorption, and early tooth loss in primary as well as mixed dentition. Here, we report treatment of a child with marginal periodontitis from the age of 3 years–7 years 9 months. No systemic manifestations were noted until 3 years of age, thus the patient had never received a detailed examination or medication related to the disease. Following examinations at our department, we referred the patient to a pediatrician at our university hospital for possible systemic disease, who made a diagnosis of autoimmune neutropenia. Although administration of antibiotics and professional dental care were continued, neutrophil count was not increased and progressive periodontal destruction was observed. Extraction of teeth with poor prognosis was performed and a prosthetic strategy for the missing teeth developed. It is important to recognize that periodontitis along with autoimmune neutropenia can appear in infants, even though the incidence is quite low. Early detection and early treatment of this disease is necessary for delaying progression of periodontitis and optimal occlusal induction of permanent teeth.     

A case of transient bioprosthetic valve regurgitation and hemolysis devoloping early after surgery using Carpentier-Edwards valve.

The Carpentier-Edwards pericardial bioprosthesis has been markedly improved in the long-term results and valve-related complications including valve dysfunction, compared to the previous generation bioprosthesis. We report a patient in whom transient prosthetic valve regurgitation and hemolysis occurred early after mitral valve replacement using a Carpentier-Edwards pericardial bioprosthesis and were resolved by preservative therapy. The patient was a 77-year-old female diagnosed with severe mitral valve stenosis and insufficiency. She underwent mitral valve replacement with a Carpentier-Edwards pericardial bioprosthesis. Opening and closing of the three leaflets looked good on intraoperative transesophageal echocardiography (TEE). The only prosthetic valve regurgitation was evident at the central region where the leaflets form coaptation, and no abnormal findings were seen. Serum lactate dehydrogenase (LDH) was decreased to 405 U/l after surgery. However, LDH again began to increase on the 3rd day after surgery and it increased to 1,830 U/l on the 14th day after surgery. Hemolytic urine was detected on 10th day after surgery. PVL was not detected, but moderate abnormal regurgitation from the outside of the stent pocket was detected on TEE. Revision of valve replacement was considered, but LDH thereafter to 393 U/l on 41st day after surgery. The TEE was repeated, and only a trace of central jet was detected without abnormal regurgitation, unlike the previous examination. The patient did not develop any complications thereafter and was discharged on 47th day after surgery. LDH was nearly normal at the time of discharge.     

The evaluation of cystoscopy in the screening of asymptomatic microhematuria

As a prospective study on asymptomatic microhematuria, complete urological examinations including cystoscopy, IVP, ultrasound and urinary cytology were performed on 422 patients over 40 years old between January 1987 and December 1988 (group A). The results of group A was compared with that of retrospective study on 266 patients, who had incomplete urological examination between January 1984 and December 1985 (group B). Cystoscopy was performed on 321 patients (87.2%) in group A and on 108 patients (40.6%) in group B. Bladder tumor was found in 10 cases (2.4%) in group A, including 7 cases of male patients (5.7%), but in only 1 case (0.4%) in group B. Since the negative rate of abnormal urinary cytology was 50% and that of abnormal IVP was 90% in 10 cases of bladder tumor in group A, cystoscopy was considered to be an essential examination for the screening of patients with asymptomatic microhematuria over 40 years old patients.     

Quantitative and qualitative changes of apolipoprotein AI-containing lipoproteins in patients on continuous ambulatory peritoneal dialysis

Using immunoaffinity chromatography, two species of apo-AI containing lipoproteins (AILp); lipoprotein containing apo-AI and apo-AII (Lp-AI/AII), and lipoprotein containing apo-AI, but no apo-AII (Lp-AI) were isolated from 13 female patients on continuous ambulatory peritoneal dialysis (CAPD), then characterized. The results were compared with findings obtained in agematched normolipidemic (control I) and mild hypertriglyceridemic (control II) female subjects. In comparison with control I: In AILp, the levels of total cholesterol (TC), cholesteryl ester (CE) and phospholipid (PL), and the levels of apoE were significantly lower in the CAPD patients while the levels of triglyceride (TG) and apo-CIII were significantly higher in these patients. The levels of apo-AI and apo-AII did not differ between the CAPD and control subjects. In Lp-AI/AII, changes of TC, CE, PL, TG, and apolipoproteins were similar to those of AILp, except for the ratio of apo-AI/apo-AII and the level of apo-CII, which was higher in the CAPD patients. In Lp-AI, changes of TC, CE, PL, and TG were also similar to those of AILp and Lp-AI/AII, but the apo-AI level was significantly lower in the CAPD patients. In comparison with control II: In AILp, the levels of PL, apo-AI, apo-AII, and apo-E were significantly lower in CAPD patients, but the apo-CIII levels were significantly higher. In Lp-AI/AII, the levels of PL and apo-E were significantly lower in CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)