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.     

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.     

Ultraflex expandable stents for the management of air leaks.

Postoperative empyema and aspergillosis were diagnosed in a 66-year-old man. Since non-operative therapy was not effective, we performed surgery. On the 8th postoperative day, a covered Ultraflex expandable stent (Boston Scientific, Galway, Ireland) was implanted to make a one-way airway for blocking a major air leak from a bronchopleural fistula causing respiratory distress. His general condition improved gradually, and he was discharged 30 days after stenting. In conclusion, we used a covered Ultraflex expandable stent to make an airway to block an air leak. This may be a new application for this stent.     

Clinical efficacy of clarithromycin in the field of pediatrics

A new macrolide antibiotic, clarithromycin (TE-031, A-56268), was studied for its clinical efficacy in the field of pediatrics. Patients treated were infants and children ranging from 2 months to 11 years old suffering from acute bronchitis in 5 cases, acute tonsillitis in 2 cases, Mycoplasma pneumonia in 2 cases, pertussis in 6 cases, scarlatina in 1 case and acute enteritis in 2 cases, a total of 18 cases. TE-031 was administered 19.7-43.5 mg/kg in daily doses and lengths of treatment ranged from 4 to 19 days. As regards to its clinical efficacy, good or excellent results were obtained in all cases: excellent in 11 cases and good in 7 cases. No clinical side effects nor abnormal laboratory test values obviously attributable to TE-031 were observed.     

Clinical background of cases showing a positive culture of pleural effusion at Shin-Kokura Hospital over a period of 5 years

We investigated the clinical background of patients at Shin-Kokura Hospital who showed a positive culture of pleural effusion during the period from January 1998 through December 2002. Microorganism cultures of the pleural effusions of 127 patients were performed in this 5-year period. Seventeen patients showed a positive microorganism culture from a pleural effusion, and 12 of these patients (70.6%) were 60 years old or more. Ten patients were diagnosed with thoracic empyema. Thirteen patients had an underlying disease such as malignancy (5 cases), diabetes mellitus (4 cases), etc. A purulent effusion and a high concentration of lactic dehydrogenase (LDH) in the pleural fluid were more frequently recognized in the positive-culture group. A total of 21 strains of microorganism were isolated from the 17 patients, including 10 strains of Gram-positive cocci, 6 strains of Gram-negative bacilli, 3 strains of anaerobes, 1 strain of mycobacterium (Mycobacterium tuberculosis), and 1 strain of fungus. Susceptibility to antimicrobial agents was generally good for most of the microorganisms isolated. Of the 17 patients, chest-tube drainage was performed in 13, and 6 needed a surgical operation. Twelve patients improved, but 5 died. In this study, thoracic empyema accounted for 58.8% of the 17 cases with a positive culture of pleural effusion. Of the 10 thoracic empyema patients, 5 patients needed surgical treatment in spite of adequate antimicrobial treatment and chest-tube drainage. Our data indicate that thoracic empyema is still difficult to treat, and thus adequate and rapid treatment is needed for any pleural infection.