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.     

Idiopathic myointimal hyperplasia of mesenteric veins: Rare case of ischemic colitis mimicking inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76‐year‐old Japanese man presented to our hospital with a 1‐year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C‐reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.     

Regional fractional ventilation mapping in spontaneously breathing mice using hyperpolarized 129Xe MRI

The feasibility of ventilation imaging with hyperpolarized (HP) ¹²⁹Xe MRI has been investigated for quantitative and regional assessment of ventilation in spontaneously breathing mice. The multiple breath ventilation imaging technique was modified to the protocol of spontaneous inhalation of HP ¹²⁹Xe delivered continuously from a ¹²⁹Xe polarizer. A series of ¹²⁹Xe ventilation images was obtained by varying the number of breaths before the ¹²⁹Xe lung imaging. The fractional ventilation, r, was successfully evaluated for spontaneously breathing mice. An attempt was made to detect ventilation dysfunction in the emphysematous mouse lung induced by intratracheal administration of porcine pancreatic elastase (PPE). As a result, the distribution of fractional ventilation could be visualized by the r map. Significant dysfunction of ventilation was quantitatively identified in the PPE‐treated group. The whole‐lung r value of 0.34 ± 0.01 for control mice (N = 4) was significantly reduced, to 0.25 ± 0.07, in PPE‐treated mice (N = 4) (p = 0.038). This study is the first application of multiple breath ventilation imaging to spontaneously breathing mice, and shows that this methodology is sensitive to differences in the pulmonary ventilation. This methodology is expected to improve simplicity as well as noninvasiveness when assessing regional ventilation in small rodents. Copyright © 2014 John Wiley & Sons, Ltd.     

Agminated fibroblastic connective tissue nevus in a 1‐year‐old boy

Fibroblastic connective tissue nevus (FCTN) is a benign cutaneous mesenchymal lesion characterized by proliferation of CD34‐positive fibroblastic/myofibroblastic spindle‐shaped cells. We report a case of agminated FCTN on the right lower abdomen of a 1‐year‐old boy.     

Multi-center analysis of calcinosis in children with juvenile dermatomyositis]

OBJECTIVES: To reveal the frequency and the clinical characteristics of dystrophic calcification that occurs in children with juvenile dermatomyositis, multi-center analysis was constructed. METHOD: Fifty children with JDM were enrolled, and 14 of them (28.0%) were complicated with calcinosis. Clinical symptoms and laboratory tests at onset, initial therapy and disease course were compared in children with and without calcinosis. RESULTS: The mean age of the onset of calcinosis was 4.78 +/- 3.33 years, and it was younger than those of children without calcinosis (8.66 +/- 3.85 years) (P = 0.0017). No differences of clinical manifestation except Gower's sign were observed. The frequency of positive anti-nuclear antibody was 7.1% in children with calcinosis and 52.9% without calcinosis (P = 0.0112). The initial therapy of methylprednisolon pulses gave no effects on prognosis of calcium deposition. The calcinosis appeared in 1.56 +/- 1.91 year after the onset of the disease. The various types of calcium deposition including large tumorous clumps, subcutaneous plaques or nodules, sheet-type calcification were deserved. They appeared over knee joints (64.3%), elbow joint (64.3%), and hip processes (50.0%). Calcinosis affecting the subcutaneous tissues frequently resulted in painful superficial ulceration of the overlying skin (42.9%), local infection (50.0%), and limitation of joint movement (14.3%). Although aluminum phosphate was effective in 2 children among 7, no other effective treatment was recommended. In 5 cases, surgical removal of tumorous clumps was operated. Thus, juvenile dermatomyositis is frequently complicated with calcinosis. This type of calcinosis was found to be unlikely to resolve completely, and resulted in severe disability in children.     

Effects of gallamine on the contractile response of the stomach in cats

Stimulation of the vagal trunk in cats anesthetized with pentobarbital sodium produced a contractile response of the stomach during stimulation (initial contraction). Pretreatment with either hexamethonium (0.3 to 30 mg/kg, i.v.) or gallamine (1 to 100 mg/kg, i.v.) dose-dependently produced a delayed contraction, following the initial contraction after stimulation. After the administration of either hexamethonium or gallamine produced a maximum delayed contraction, then an additional dose of gallamine or hexamethonium was administered. The subsequent treatment further augmented the delayed contraction. The results indicate that gallamine induced the delayed contraction by a mechanism different from hexamethonium.