Objective: Since the conventional drip-infusion method for measuring inulin clearance (Cin) has problems related to its accuracy and performance, we explored a more accurate and concise method by rapid intravenous injection of a newly developed inulin fraction (Inulead^®), in which spot urine sampling was omitted and the administration period of inulin was shortened from 120 to 5 minutes. Patients and Methods: Twenty seven patients (M/F: 15/12, 67.8 ± 12.9 years old) admitted to the Nephrology ward were enrolled in this study. Inulead^®, 1500 mg dissolved in 150 mL of saline, was intravenously administered in 5 minutes. Then, sequential blood samplings and urine collection were performed for 24 hours. Cins were calculated by the following three formulae: (1) a pharmacokinetic analysis using a two compartments model based on the plasma inulin concentration to determine Cin, which was the administered dose divided by the area under the curve (AUC) from 0 to ∞, (2) urinary inulin excretion divided by the AUC for 24 hours and (3) the Bayesian method using a three-point set of plasma inulin concentrations to predict the change of inulin concentration to determine Cin as in 1. These Cins were compared with levels of estimated GFR (eGFR), creatinine clearance (Ccr), serum β2 microglobulin (β2MG) and serum cystatin C (Cys C). Results: Cins obtained by the above three methods were well correlated with each other (r. = 0.9088 – 0.9998) and with eGFR (r. = 0.8286 – 0.8650), Ccr (r. = 0.821 – 0.864), 1/β2MG (r. = 0.631 –0.752) and 1/CysC (r. = 0.830 – 0.857). The averaged differences of each Cin from eGFR were distributed between –4.4 and –4.5 mL/min. Conclusion: Since the Cins by rapid inulin injection showed satisfactory correlation and differences with other GFR parameters, this method will be a good alternative to the drip infusion method, and may reduce the burden of patients and medical staff.

The initial case was a man in his 50s. He received 2 cans a day of ProSure^®, while undergoing radiation and chemotherapy with carboplatin and docetaxel for adenocarcinoma in the lung. His body weight rose from 62.4 kg on admission to 63.7 kg before discharge, CRP decreased from 3.08 mg/dl to 0.48 mg/dl, and albumin fell from 3.6 g/dl to 3.5 g/dl. The second case was a man in his 60s. He was diagnosed as having squamous cell carcinoma in the lung and administered with 2 cans a day of ProSure^® and antibiotics. One-and-a-half months later, he underwent chemotherapy with carboplatin and S-1 and radiation. His body weight stood at 47.0 kg on admission and 47.2 kg before discharge, CRP dropped from 15.45 mg/dl to 3.26 mg/dl, and albumin was retained at 2.6 g/dl to 2.7g/dl. The administration of ProSure^® brought about improvements in the nutritional status and anti-inflammatory effects in the patients with chemotherapy.

The utilization of generic drugs in medical practice has been promoted in Japan for the purpose of minimizing drug costs. In order to determine the clinical efficacy of the original preparation of glycyrrhizin, in comparison to its generic drug, a controlled longitudinal study was done of 82 consecutive patients with chronic hepatitis C receiving the original preparation of glycyrrhizin for 6 months. Patients treated with the original preparation of glycyrrhizin for 6 months at two hospitals were separated into two groups for study: Patients who changed from the original preparation of glycyrrhizin to a generic drug and then changed back from the generic drug to the original preparation of glycyrrhizin (Group A, n=46) ; and, patients who were continuously treated with the original preparation of glycyrrhizin (Group B, n=36) . HCV RNA levels were serially determined by Cobas Amplicor HCV Monitor assay. In Group A, the ALT level significantly elevated 3 months after switching treatment from the original preparation of glycyrrhizin to the generic drug (from 65.1 ±22.7 IU/L to 1 12.4±39.9 IU/L) (P<0.05), then significantly decreased 3 months after the change back to the original preparation of glycyrrhizin (from 112.4±39.9 IU/L to 62.1±23.0 IU/L) (P<0.05) . In Group B, however, the ALT level did not significantly change during the same observation period. The serum HCV RNA level did not significantly change in either group, even in Group A patients whose ALT levels significantly changed. The efficacy on ALT of the original preparation of glycyrrhizin and the generic drugs differed in patients with chronic hepatitis C.

Objective. We investigated whether the aging-related decrease in gap junction expression affects myocardial response against ischemia-reperfusion injury of the rabbit myocardium. Methods. Isolated aged (≥135 weeks) or mature (15-20 weeks) rabbit hearts were perfused with Krebs-Henseleit solution via a Langendorff apparatus, and were divided into five groups as follows: 7 mature hearts served as mature controls (Group A), 7 mature hearts underwent ischemic preconditioning (IPC) consisting of two cycles of global ischemia for 5min followed by reperfusion for 5min (Group B), 7 aged hearts served as aged control (Group C), 7 aged hearts underwent IPC (Group D) and 7 mature hearts received 1mM of gap junction uncoupler heptanol for 5min (Group E). Then, all hearts were subjected to 1h of left anterior descending coronary artery occlusion followed by 1h of reperfusion. Left ventricular pressure, ischemic zone monophasic action potential and coronary flow were measured throughout the experiment and the infarct size (IS) was determined at the end of the experiment. Gap junction expression was investigated by the electron microscopy. Results. The IS of Group A was 39.1±3.8 (%) and that of Group B was 26.9±3.8 (%)^* (^*p<0.05 vs. Group A). The IS of Group C was 19.3± 1.6(%)^*. That of Group D was 43.6±5.8 (%)^# (^#p<0.05 vs. Group C). IS of Group E was 24.3±1.6 (%)^*. Electron microscopic findings demonstrated that gap junction expression in aged hearts was less prominent than in mature ones. Conclusion. These data suggested that aged myocardium might be more tolerant of ischemic insult than that of mature heart, and that the mechanism might be related to the aging-related change of gap junction expression.

Objective: Treatment of tinea unguium with topical drugs alone is difficult, and medication with oral terbinafine hydrochloride is necessary in many cases.  Since Trychophyton infects the nails in not only men but also women at a reproductive age, the influence on a fetus of the drug ingested during early pregnancy is a matter of concern of many women.  The objective of this study was to investigate the influence of oral terbinafine hydrochloride on fetuses.
Methods: The outcomes were investigated in pregnant women who ingested terbinafine hydrochloride and visited the ‘Outpatient Services for Consultation on Pregnancy and Drugs (Teratology Information Services)’ of Toranomon Hospital, and cases were collected.
Results: Fifteen pregnant women ingested the drug during the organogenic period, in which the teratogenic risk is the highest.  All 15 pregnant women gave birth to healthy babies.
Conclusion: This is the first survey concerning newborns delivered by women who ingested terbinafine hydrochloride during pregnancy in Japan.  All investigated women gave birth to healthy babies, and the incidence of congenital abnormalities did not markedly exceed that in the general population.  Since the number of cases was small, it is necessary to perform a cohort study to investigate details of the safety for fetuses.

Objective: Novel antipsychotic agents less frequently cause extrapyramidal side effects compared to conventional antipsychotic agents, contributing to improvement in the QOL.  Recently, these agents have also been increasingly prescribed to females who may become pregnant.  In Japan, no epidemiological survey regarding the application of novel antipsychotic agents in pregnant women has been published.  In this study, we investigated the influence on fetuses in pregnant women receiving novel antipsychotic agents.
Methods: In pregnant women on novel antipsychotic agents who consulted the Pregnancy and Drug Consultation Outpatient Clinic of Toranomon Hospital, the outcome of pregnancy was confirmed.
Results: Twenty-nine pregnant women took novel antipsychotic agents in the organogenesis phase, in which the risk of teratogenicity is the highest.  The agents consisted of olanzapine in 8 patients, risperidone in 11, quetiapine fumarate in 7, and perospirone hydrochloride hydrate in 4.  The outcomes of pregnancy were full-term delivery in 24 patients, premature delivery in 1, spontaneous abortion in 2, and artificial abortion in 2.  Of the 29 patients, 15 (60%) had continuously taken these agents until delivery.  All 25 neonates were healthy without malformation.
Conclusion: This report describes the first prospective survey in Japan regarding infants delivered by pregnant women receiving novel antipsychotic agents.  All patients delivered healthy neonates; the incidence of congenital anomalies did not exceed that in the general population.  This survey included a small number of patients; cohort studies should be conducted to evaluate the safety in fetuses.

From January 1979 through May 1982, 36 premature infants less than 2.5kg and less than 35 weeks of gestation, including 24 patients with respiratory distress syndrome, underwent ligation of patent ductus arteriosus (PDA) due to being unresponsive to medical treatment. Ten patients died postoperatively mainly from intracranial hemorrhage and necrotizing enterocolitis. Surviving 26 patients were examined for developmental sequelae based on questionnaire survey. One infant died of respiratory failure secondary to severe bronchopulmonary dysplasia 28th month after operation. We found no evidence of recurrent ductal patency following ligation during the follow-up period. Twenty four patients exhibited normal motor and mental development to attend the ordinary elementary school everyday, but one patient shows mental retardation. Most of patients suffered from the frequent upper respiratory infection in childhood to require rehospitalization. There are no patients with hoarseness, but 2 patients developed funnel chest and one required the operation. One third of the patients had ophthalmological handicap (myopia or strabismus). Surgical ligation of PDA in premature infants seems to reduce the duration of postoperative mechanical ventilation and the incidence of bronchopulmonary dysplasia. Analyzing long-term follow-up indicates that infants who undergo PDA ligation grow almost normally and do not appear to be at increased risk for sensorineural handicaps. Therefore we emphasize that surgical ligation of PDA is an effective and appropriate treatment of choice for significant PDA in premature infants.

BACKGROUND/AIMS: Helicobacter pylori infection causes gastritis, peptic ulcers and gastric malignancies, and its eradication has been advocated by many groups. We determined the H. pylori carrier status and eradication rates of patients with chronic hepatitis C virus (HCV) infection. METHODS: In total, 76 chronically HCV-infected patients were enrolled for comparison with 228 HCV-noninfected, age- and sex-matched controls. H. pylori infection was confirmed by H. pylori antibody and urea breath testing. RESULTS: The H. pylori infection rate was significantly higher for HCV-infected patients (67 of 76, 88.2%) than for HCV-noninfected controls (158 of 228, 69.3%). Endoscopic findings showed that the rates of gastric ulcers and gastritis were significantly higher for the 67 HCV-infected patients with H. pylori infection (34.3% and 77.6%) than for the 158 HCV-noninfected controls with H. pylori infection (15.2% and 57.6%). Treatment to eradicate H. pylori had a significantly higher success rate for HCV-infected patients (61 of 67, 91.0%) than for HCV-noninfected controls (115 of 158, 72.8%). CONCLUSIONS: The markedly high H. pylori eradication rate observed in this study shows that eradication of H. pylori holds promise for the improvement of the long-term health condition of patients with chronic HCV infection.
Gastritis ; Helicobacter ; Helicobacter pylori ; Hepatitis C, Chronic ; Hepatitis, Chronic ; Humans ; Peptic Ulcer ; Stomach Ulcer ; Urea ; Viruses

This review is partly composed of the presentation "Cytokine alteration and speculated immunological pathophysiology in silicosis and asbestos-related diseases" delivered during the symposium "Biological effects of fibrous and particulate substances and related areas" organized by the Study Group of Fibrous and Particulate Studies of the Japanese Society of Hygiene and held at the 78th Annual Meeting in Kumamoto, Japan. In this review, we briefly introduce the results of recent immunological analysis using the plasma of silica and asbestos-exposed patients diagnosed with silicosis, pleural plaque, or malignant mesothelioma. Thereafter, experimental background and speculation concerning the immunological pathophysiology of silica and asbestos-exposed patients are discussed.

Clinical course and outcome of 34 patients with peripheral and visceral artery aneuryms, operated during 1975-1990, were analysed. There were 24 males and 10 females. Ages ranged from 14 to 87, with an average of 55 years. Peripheral aneurysms located most frequently in the lower extremity, and the incidence of various origin of the aneurysms were as follows: 14 in femoral, 5 in popliteal, 4 in internal iliac, 3 in subclavian, 2 in common iliac arteries, and 1 in each of vertebral, radial, splenic, renal and anterior tibial artery. Most common cause of aneurysm was arteriosclerosis. Multiple aneurysms were found in 59% of sclerotic type and in most of these with bilateral aneurysms in the iliac, femoral and popliteal. Ruptured aneurysms were seen in 26% of this series. Most of the aneurysms in the extremities were totally excised without difficulty, while the aneurysms in common iliac and internal iliac were opened with partial excision or obliterated with endoaneurysmorrhaphy. Arterial reconstruction was performed using saphenous vein graft or synthetic vascular graft, excepting that the internal iliac artery itself was not reconstructed. The early operative results were satisfactory, but late results showed two death and three complications of cardiovascular system. Therefore, careful follow up of the postoperative patients was recommended.