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Strongyloidiasis, an intestinal parasitic infection caused by Strongyloides stercoralis, rarely occurs in Japan. When treated with immunosuppressive drugs, two potentially lethal conditions, hyperinfection and dissemination, may develop in asymptomatic carriers of this parasite. We report the development of strongyloidiasis during treatment of polymyositis with glucocorticoids plus rituximab (RTX). A 44-year-old woman had been diagnosed with anti-signal recognition particle antibody–positive polymyositis with interstitial pneumonia 6 years previously, for which she had recently been receiving prednisolone at 5 mg/day and RTX at 375 mg/m2 twice every 3 months. Her condition appeared to be well controlled. She was admitted to our hospital with a 1-month history of chronic diarrhoea and epigastric pain. Standard microscopic examination of a sample of faeces revealed the presence of S. stercoralis; however, serologic testing for parasites was negative. Treatment with ivermectin alleviated her inflammatory diarrhoea and eradicated the faecal parasites. We believe that our patient had an exacerbation of S. stercoralis infection (hyperinfection syndrome) that was exacerbated by low-dose glucocorticoids plus RTX. Strongyloidiasis should be considered in immunocompromised individuals with unexplained diarrhoea, even in non-endemic areas.

Patient: Male, 84 Final Diagnosis: Intramural hematoma of esophagus Symptoms: Chest pain • hematemesis Medication: — Clinical Procedure: Esophagogastroduodenoscopy Specialty: Gastroenterology and Hepatology Objective: Diagnostic/therapeutic accidents Background: Intramural hematoma of the esophagus (IHE), a rare manifestation of acute mucosal injuries of the esophagus, can be caused by trauma such as endoscopic surgeries. Coagulation disorders increase the risk of IHE. The most common location of IHE is in the distal esophagus. The characteristic clinical triad of manifestations comprises acute retrosternal pain, odynophagia or dysphagia, and hematemesis. It is important to distinguish IHE from other acute conditions such as acute coronary syndrome, aortic dissection, and pulmonary embolism. Case Report: An 84-year-old male was scheduled for coil embolization for an endoleak after endovascular aneurysm repair. For this reason, he was taking aspirin and warfarin. A nasogastric tube had been inserted during surgery and subsequently removed without any problems reported. Postoperatively, he experienced chest pain and hematemesis of sudden onset. Urgent esophagogastroduodenoscopy demonstrated a large, dark red, non-pulsatile, submucosal, esophageal mass in the area of the mid-esophagus with a little oozing. He was diagnosed as having an IHE; other possible diagnoses were excluded by contrast-enhanced computed tomography and aortography. He was treated with fasting, a proton pump inhibitor, and cessation of anti-thrombotic drugs; he recovered completely. The bleeding spot in the esophagus was in the area of the mid-esophagus, which was around the second natural constriction site. It was possible that the nasogastric tube had contact with the esophageal wall at this second natural constriction, and caused intramural esophageal bleeding. Conclusions: Nasogastric tubes are not generally recognized as a cause of IHE. However, they can cause them, especially when a patient is taking anti-thrombotic drugs.

Introduction This study evaluated the impact of a telephone support programme with telemonitoring on changes in healthy eating and active exercise in adults with prediabetes using the stage of change framework. Methods We performed a post hoc analysis using data from the Japan Diabetes Outcome Trial-1. A total of 2607 participants aged 20–65 years with impaired fasting glucose were recruited from the workplace/community in Japan and randomized to a one year telephone support programme intervention arm ( n = 1240) or self-directed control arm ( n = 1367). Participants in both arms received monthly data feedback from a weight scale and pedometer. The main outcome measure was the stages of change toward healthy eating and active exercise. The secondary outcome was fasting plasma glucose (FPG). Results After the one year intervention, the adjusted odds ratio of progressing to the action/maintenance stage in the intervention vs. control arm for healthy eating was 1.31 (95% confidence interval (CI) 1.21–1.43; p Discussion These findings suggest that the telephone support programme by healthcare providers advanced the stage of changes toward healthy eating in people with prediabetes. In particular, it decreased FPG levels in the contemplation stage.

Background There is limited quantitative research on the effect of physician attire on patient–physician relationships. This study aimed to measure the influence of Japanese family physicians’ attire on the “human” aspects of medical care in terms of patient-perceived relational empathy. Methods This was a multicenter, prospective, controlled trial conducted in primary clinics in Japan. We explored the effects of family physician attire (white coat vs. casual attire) on patient-perceived empathy. Family physicians were allocated to alternate weeks of wearing a white coat or casual attire during consultations. Patients’ perceptions of physician empathy were evaluated using the self-rated Japanese Consultation and Relational Empathy (CARE) Measure. We used a linear mixed model to analyze the CARE Measure scores, adjusting for cluster effects of patients nested within doctor, age, and sex of patients, and doctors’ sex and years of clinical experience. We used the same method with Bonferroni adjustment to analyze patient sex differences in perceived empathy. Results A total of 632 patients of seven family physicians were allocated to white coat-wearing consultations (n = 328), and casual attire-wearing consultations (n = 304). There was no difference in CARE Measure scores between white coat and casual primary care consultations overall (p = 0.162). Subgroup analysis of patient sex showed that CARE Measure scores of male patients were significantly higher in the Casual group than in the White coat group (adjusted p-value = 0.044). There was no difference in female patient scores between White coat and Casual groups (adjusted p-value = 1.000). Conclusions This study demonstrated that physician attire (white coat or casual attire) in a primary care setting did not affect patient-perceived relational empathy overall. However, male patients of physicians wearing casual attire reported higher physician empathy. Although empathy cannot be reduced to simple variables such as attire, white coats may have a negative effect on patients, depending on the context. Family physicians should choose their attire carefully. Trial registration Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000037687 (Registered August 14, 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042749). The study was prospectively registered.

Many studies have examined the impression made on patients by physicians’ attire. Regardless of practice location, many patients express most confidence in physicians who wear white coats. The number of physicians in Japan who choose not to wear white coats in practice has been increasing, particularly in primary care settings. However, very few studies have examined physician preference for attire. To clarify Japanese general practitioners’ preference for attire by practice setting, we conducted a survey of physician preferences and reasons for attire selection. Subjects were 794 general practitioners certified by the Japan Primary Care Association and recruited from a mailing list. We conducted a web-based questionnaire survey. Physicians were asked to choose one of four different dress styles (semi-formal, white coat, scrubs, and casual) for different practice settings and state the reasons for selection. The response rate was 19.3% (n = 153; men 112). Most subjects chose white coats as usual attire for hospital practice (52%), mainly because of custom and professionalism. In contrast, most subjects chose non-white coats for clinics (59%) and home care (hospital-provided, 58%; clinic-provided, 71%). More subjects chose casual dress for clinic and home care practice, mainly to appear empathic. Most subjects chose white coats as the most appropriate hospital attire (54%), mainly because of patient perceptions of this attire being professional. Most subjects considered non-white coat attire more appropriate for clinic and home care practice. The findings indicate that general practitioners choose their clothes depending on practice location.

Objectives Frequent self-weighing is associated with weight loss and maintenance, but the relationship between frequent self-weighing and the incidence of type 2 diabetes (T2D) remains unclear. The study aim was to examine the association between self-weighing frequency and the incidence of T2D in people with impaired fasting glucose (IFG). Results We tested the hypothesis that self-weighing frequency and the incidence of T2D are associated in 2607 people with IFG (1240 in the intervention arm; 1367 in the self-directed control arm). Both arms received a weighing scale with storage function. Healthcare providers offered a one-year goal-focused lifestyle intervention via phone. Participants were divided into 4 categories based on self-weighing frequency (No data sent [reference group], low: Trial registration This trial has been registered with the University Hospital Medical Information Network (UMIN000000662).

Objectives Using annual health check‐up data, the aim of this study was to identify target populations for lifestyle interventions to effectively prevent diabetes in a real‐world setting. Methods The Japan Diabetes Outcome Intervention Trial‐1, a prospective, cluster‐randomized controlled trial, was launched to test if year‐long telephone‐delivered lifestyle support by health professionals can prevent the development of type 2 diabetes (T2D) in people with impaired fasting glucose (IFG) identified at health check‐ups. A total of 2607 participants aged 20‐65 years with IFG were randomized to an intervention arm (n = 1240) or a control arm (n = 1367). We performed subgroup analysis to examine the effects of the intervention on the incidence of T2D in participants with body mass index (BMI) ≥25, metabolic syndrome (MetS), and non‐alcoholic or alcoholic elevated liver enzymes at the baseline. Cox regression analysis adjusted for sex was used to calculate the hazard ratios (HRs). Results In addition to IFG, the presence of BMI ≥25, MetS, and elevated liver enzymes increased the incidence of diabetes by two‐ or three‐fold. During a median follow‐up period of 4.9 years, only the non‐alcoholic elevated liver enzyme group showed a low incidence rate owing to lifestyle interventions (adjusted HR: 0.42, 95% confidence interval: 0.18‐0.98). Conclusion The results suggest that people who have IFG and non‐alcoholic elevated liver enzymes are a good target population for lifestyle interventions to effectively reduce the incidence of diabetes in a real‐world setting.

Background: Evidence of the long-term benefits of telephone-delivered lifestyle interventions is limited. This study investigated the ability of telephone-delivered lifestyle intervention ...

Background Few studies have compared the effectiveness of brief training courses on point-of-care ultrasound (POCUS) skill acquisition of novice attending physicians vs. trainees. The purpose of this study was to evaluate the change in POCUS image interpretation skills and confidence of novice attending physicians vs. trainees after a 1-day POCUS training course. Methods A 1-day POCUS training course was held in March 2017 in Japan. A standardized training curriculum was developed that included online education, live lectures, and hands-on training. The pre-course assessment tools included a written examination to evaluate baseline knowledge and image interpretation skills, and a physician survey to assess confidence in performing specific ultrasound applications. The same assessment tools were administered post-course, along with a course evaluation. All learners were novices and were categorized as trainees or attending physicians. Data were analyzed using two-way analysis of variance. Results In total, 60 learners attended the course, and 51 learners (85%) completed all tests and surveys. The 51 novice learners included 29 trainees (4 medical students, 9 PGY 1–2 residents, 16 PGY 3–5 residents) and 22 attending physicians (6 PGY 6–10 physicians, and 16 physicians PGY 11 and higher). The mean pre- and post-course test scores of novice trainees improved from 65.5 to 83.9% while novice attending physicians improved from 66.7 to 81.5% (p

Background. Empathy is an important attribute in medicine, influencing both the process and outcome of consultations. However, there are no validated tools available in Japan to gather patient feedback on physicians’ empathy. The Consultation and Relational Empathy (CARE) Measure developed in the UK is widely used internationally. Objectives. To investigate the psychometric properties of a Japanese version of the CARE Measure. Method. Following two cycles of translation and back translation, the Japanese CARE Measure was completed by 317 patients in a primary medical care clinic in Japan. Tests of internal reliability and validity included Cronbach’s alpha, item-total correlations and factor analysis. Predicted associations between CARE Measure score and other variables were assessed by Spearman’s rho. Results. Low numbers of missing values (8.2–9.8%) and ‘not applicable’ responses (0–1.3%) suggested high acceptability and face validity of the Japanese CARE Measure. Internal reliability was high (Cronbach’s alpha 0.984) and was reduced by the removal of any of 10 items. High corrected item-total correlations (0.897–0.946) suggested homogeneity. Factor analysis showed a single solution with high item loadings (0.917–0.957). Construct validity was supported by a significant relationship (Spearman’s rho 0.74, P

Background The multiple mini-interview (MMI) is increasingly used for postgraduate medical admissions and in undergraduate settings. MMIs use mostly Situational Questions (SQs) rather than Past-Behavioural Questions (PBQs). A previous study of MMIs in this setting, where PBQs and SQs were asked in the same order, reported that the reliability of PBQs was non-inferior to SQs and that SQs were more acceptable to candidates. The order in which the questions are asked may affect reliability and acceptability of an MMI. This study investigated the reliability of an MMI using both PBQs and SQs, minimising question order bias. Acceptability of PBQs and SQs was also assessed. Methods Forty candidates applying for a postgraduate medical admission for 2016–2017 were included; 24 examiners were used. The MMI consisted of six stations with one examiner per station; a PBQ and a SQ were asked at every station, and the order of questions was alternated between stations. Reliability was analysed for scores obtained for PBQs or SQs separately, and for both questions. A post-MMI survey was used to assess the acceptability of PBQs and SQs. Results The generalisability (G) coefficients for PBQs only, SQs only, and both questions were 0.87, 0.96, and 0.80, respectively. Decision studies suggested that a four-station MMI would also be sufficiently reliable (G-coefficients 0.82 and 0.94 for PBQs and SQs, respectively). In total, 83% of participants were satisfied with the MMI. In terms of face validity, PBQs were more acceptable than SQs for candidates (p = 0.01), but equally acceptable for examiners (88% vs. 83% positive responses for PBQs vs. SQs; p = 0.377). Candidates preferred PBQs to SQs when asked to choose one, though this difference was not significant (p = 0.081); examiners showed a clear preference for PBQs (p = 0.007). Conclusions Reliability and acceptability of six-station MMI were good among 40 postgraduate candidates; modelling suggested that four stations would also be reliable. SQs were more reliable than PBQs. Candidates found PBQs more acceptable than SQs and examiners preferred PBQs when they had to choose between the two. Our findings suggest that it is better to ask both PBQs and SQs during an MMI to maximise acceptability. Electronic supplementary material The online version of this article (doi:10.1186/s12909-017-0898-z) contains supplementary material, which is available to authorized users.

Aim of the study Acanthopanax senticosus Harms extract (ASE) is used as an ingredient of over-the-counter drugs and functional foods, such as health supplements, in Japan. ASE exhibits a hypoglycemic effect; however, the mechanism of the hypoglycemic effect is not clear. In the present study, we investigated whether ASE has a glucose absorption inhibitory action. Materials and methods We examined the effects of ASE on α-amylase and α-glucosidase activities, and on glucose uptake in Caco-2 cells. We also examined the effects of ASE oral administration on glucose tolerance in type 2 diabetes mellitus model db/db mice. Results The addition of ASE inhibited α-glucosidase activity but not α-amylase activity. The α-glucosidase inhibitory activity of ASE was approximately 1/13 of that of acarbose. The addition of ASE inhibited 2′-deoxy- d -glucose (DG) uptake in human intestinal Caco-2 cells, and the inhibitory activity of ASE was approximately 1/40 of that of phloretin. Kinetic analysis of glucose uptake indicated that ASE has no effects on DG uptake through passive diffusion, but that ASE inhibits intracellular DG uptake chiefly by inhibiting transport via a glucose transporter. In the glucose tolerance study, db/db mice orally administered ASE for 3 days showed significantly lower plasma glucose level than the control group 30 min after sucrose loading, without affecting plasma insulin levels. In addition, ASE oral administration significantly inhibited α-glucosidase activity in the small intestine mucosa extirpated from the mice. Conclusion These findings indicate that ASE may be useful as an ingredient of functional foods to improve postprandial hyperglycemia and prevent type II diabetes mellitus.

Acanthopanax senticosus HARMS (AS) is used as a Chinese herbal medicine and as a health supplement in Japan. However, little is known about the interaction between AS and other drugs. In this study, we investigated the effect of AS extract on intestinal drug transporter (P-glycoprotein, or P-gp) and peptide transporter activities in Caco-2 cells. Caco-2 cells were cultured on a culture dish and a permeable membrane for 1-3 weeks. The apical-to-basolateral (A-to-B) transport of digoxin, a P-gp substrate, was significantly increased by the addition of AS extract in a concentration-dependent manner. In contrast, the A-to-B transport of cephalexin, a peptide transporter substrate, was significantly decreased by the addition of AS extract in the same manner. The effects of AS extract addition on the kinetics of the uptake of rhodamine 123, a P-gp substrate, and Gly-Sar, a peptide transporter substrate, were investigated. V (max) for rhodamine 123 uptake was significantly increased by AS extract addition compared with the control, whereas that for Gly-Sar uptake was significantly decreased. On the other hand, K (m) and K (d) for rhodamine 123 and Gly-Sar uptake were not affected. We conducted further investigations to clarify the effect of AS extract addition on P-gp activity. When AS extract was added to the apical side, B-to-A transport of rhodamine 123 was significantly decreased compared with the control. Furthermore, the amount of intracellular rhodamine 123 was increased by AS extract addition compared with the control. These results suggest that P-gp and peptide transporter activities are suppressed by AS extract addition in a non-competitive manner.

Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, the enzyme catalyst for the second step of the BCAA catabolic pathway, plays a central role in the regulation of BCAA catabolism. The activity of the complex is regulated by a covalent modification cycle in which phosphorylation by BCKDH kinase inactivates and dephosphorylation by BCKDH phosphatase activates the complex. Many studies suggest that control of the activity of the kinase is a primary determinant of the activity of the complex. The kinase exists at all times in the mitochondrial matrix space in two forms, with a large amount being free and a smaller amount bound rather tightly to the BCKDH complex. Only the bound form of the kinase appears to be catalytically active and, therefore, responsible for phosphorylation and inactivation of the complex. alpha-Ketoisocaproate, the transamination product of leucine and the most important known physiological inhibitor of BCKDH kinase, promotes release of the kinase from the complex. alpha-Chloroisocaproate, the analogue of leucine and the most potent known inhibitor of the kinase, is more effective than alpha-ketoisocaproate in promoting release of BCKDH kinase from the complex. Exercise and chronic liver disease (liver cirrhosis) likewise decrease the amount of the kinase bound to the complex in rat liver. The resulting activation of the BCKDH complex appears responsible for the increase in BCAA catabolism caused by exercise and liver cirrhosis. Our findings support the use of BCAA supplements for patients with liver cirrhosis.

To compare the sensitivity, specificity, and total accuracy of an HbA1c ofor =6.5% in the detection of hyperglycemia (PPHG) relative to those of a fasting blood glucose (FBG) ofor =7.0 mmol/L.A total of 6,010 subjects (2,987 men and 3,023 women) living or working in Kasugai, Japan, underwent a medical checkup at Kasugai City Medical Care Center between April 2001 and March 2002. For the 91 subjects who had either a FBG ofor =7.0 mmol/L or an HbA1c ofor =6.5%, a 75-g oral glucose tolerance test was performed to confirm or exclude PPHG. We calculated the true- and false-positive odds ratios to evaluate the sensitivity and specificity of HbA1c relative to FBG, and compared the overall accuracy by calculating the conditional relative odds ratio (CROR).Among the 91 subjects, the true- and false-positive odds ratios were 0.43 (95% CI 0.26-0.69) and 0.40 (0.13-1.27) (Fisher's exact test, P.090), respectively; the CROR was 1.07 (95% CI 0.30-3.75).Although the HbA1c test was marginally more specific but less sensitive than the FBG test, at the given cutoff points the accuracies of two tests were equivalent.

The discriminating abilities of fasting plasma glucose (FPG) and HbA1c were compared on screening tests for impaired glucose tolerance (IGT) and IGT plus diabetes mellitus by the receiver operating characteristic (ROC) curve analysis. Furthermore, effects of sex, age and BMI were examined on sensitivity and specificity of the optimal cutoff points. This study included 997 subjects who were recruited for 75 g OGTT after the first screening of the Japan Diabetes Prevention Program. According to the 1997 criteria of the American Diabetes Association (ADA), 140 subjects were classified as diabetic and 256 as IGT. The areas under the ROC curves of FPG were significantly larger than those of HbA1c. The optimal cutoff points of FPG were 102 mg/dl for IGT and 105 mg/dl for IGT plus diabetes mellitus. Those of HbA1c were both 5.3%. In screening with FPG, females had significantly lower sensitivity and higher specificity than males, and the specificity for IGT plus diabetes mellitus was the lowest in the obese group. In screening with HbA1c, the specificity was low in the older and the obese groups. We concluded that FPG was superior to HbA1c for screening of IGT and IGT plus diabetes mellitus and the optimal cutoff point of FPG would be 102 mg/dl or greater.

Little is known about the regulatory effects of steroid hormones on the intestinal H(+)/oligopeptide transporter PEPT1. In the present study, we investigated the effects of progesterone and its related compounds on the uptake of cephalexin, a typical PEPT1 substrate, using the human intestinal cell line Caco-2. Caco-2 cell monolayers were cultured on plastic cell culture plates coated with rat tail collagen type I. The determination of cephalexin uptake was performed with HPLC. To investigate the effect of progesterone treatment on cephalexin uptake, the monolayers were incubated with cephalexin after progesterone treatment. Progesterone decreased cephalexin uptake in a concentration-dependent manner, and the IC(50) value was calculated to be 2.3 microM. A significant decrease in cephalexin uptake was observed after progesterone treatment for 12 h, and the decrease was maximal when the monolayers were treated for 24-72 h. Cephalexin uptake was significantly inhibited by treatments with 17alpha-hydroxyprogesterone, norethisterone, and chlormadinone. By contrast, treatment with dehydroepiandrosterone, pregnenolone, estradiol, testosterone, hydrocortisone, and dexamethasone did not affect cephalexin uptake. The effects of progesterone and norethisterone treatment on the kinetic parameters of cephalexin uptake were investigated. The saturable component of cephalexin uptake was markedly inhibited by progesterone and norethisterone treatments. The J(max) of cephalexin uptake with progesterone and norethisterone treatments was significantly decreased compared with the control, whereas K(m) and K(d) values were not affected. Therefore the quantitative decrease in PEPT1 density is considered to be one cause of the decrease in cephalexin uptake with progesterone and norethisterone treatments.

We investigated whether cephalexin transport in Caco-2 cells is regulated by insulin. After the insulin pretreatment, cephalexin uptake, and transport as well as PEPT1 mRNA and protein expression in the cells were measured. Cephalexin uptake was significantly increased by the insulin pretreatment. Insulin significantly increased cephalexin saturable uptake, but had no significant effect on the non-saturable one. PEPT1 protein expression on the apical membrane, but not PEPT1 mRNA expression, was increased by the insulin pretreatment. The enhancement of cephalexin uptake by the insulin pretreatment was inhibited by genistein, a tyrosine kinase inhibitor, and colchicine, an agent that disrupts protein translocation. Apical-to-basolateral transport of cephalexin has increased by the insulin pretreatment at the apical side and long-term insulin pretreatment at the basolateral side. It is considered that insulin mainly binds to its receptor on the apical and basolateral membranes, thereby promoting PEPT1 translocation from the intracellular pool to the apical membrane surface; consequently, PEPT1 protein expression on the apical membrane is increased.

Objective: To clarify the influences of age on dietary intakes and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. Subjects and methods: In autumn 1996, we estimated dietary FA intakes based on 7 day weighed diet records and analyzed plasma FA concentrations in 79 healthy Japanese female dietitians, and investigated their relationships with age, dividing into three age groups (young (32–42 y), middle-aged (43–50 y) and elderly (51–66 y)). Results: Dietary intakes of total FA, saturated FAs, monounsaturated FAs, n-3 polyunsaturated FAs (PUFAs) and α-linolenic acid (18:3n-3) were significantly highest in the middle-aged group, and lowest in the elderly. Similar trends were observed for dietary intakes of n-6 PUFAs and linoleic acid (18:2n-6), but there were no differences with regard to eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3) and n-3 highly unsaturated FAs (HUFAs=EPA+22:5n-3+DHA). On the other hand, plasma concentrations of all FAs except for arachidonic acid (20:4n-6) demonstrated positive correlations with age. Moreover, plasma concentrations of EPA in all age groups, DHA in the elderly and n-3 HUFAs in the middle-aged and the elderly were all positively correlated with dietary intakes. Conclusions: We should take into account the influence of age on dietary habit and lipid metabolism when interpreting associations between dietary FA intakes and plasma FA concentrations. Sponsorship: This study was supported in part by a grant-in-aid from the Ministry of Education, Science, Sports, Culture and Technology, Japan (06454242).

We investigated whether the uptake of a specific antipsychotic agent, sulpiride, in Caco-2 cells is mediated by a carrier-mediated system. Caco-2 cell monolayers were cultured in plastic culture dishes and uptake and efflux studies were conducted. The determination of sulpiride was performed by HPLC. At 37 degrees C, sulpiride uptake in pH 6.0 was twice as much as in pH 7.4. At 4 degrees C, however, no significant difference was observed between pH 6.0 and 7.4. The uptake at 4 degrees C was markedly lower than that obtained at 37 degrees C. The subtraction of the uptake at 4 degrees C from the uptake at 37 degrees C indicated a saturable process, and the result of the Eadie-Hofstee plot analysis indicated that the uptake consists of two or more saturable components. The uptake was significantly inhibited by uncoupler, protonophore, amino acid modifying agent and proteinase. Sulpiride efflux was temperature-dependent and was significantly inhibited by uncoupler and amino acid modifying agent. These findings indicate that sulpiride uptake and efflux in Caco-2 cells are carrier-mediated. Furthermore, the uptake was significantly decreased by some substrates and inhibitors of peptide transporter, PEPT1, and organic cation transporters, OCTN1 and OCTN2, and was significantly increased by preloading with them. The uptake was also significantly increased by a typical substrate of P-glycoprotein. From these findings, we presumed that peptide transporter PEPT1 and organic cation transporters OCTN1 and OCTN2 are involved with this uptake. P-glycoprotein may also contribute to the efflux of sulpiride.

Objective: To assess the relative validity of a semi-quantitative food frequency questionnaire (SQFFQ) against 28 day weighed diet records (WDRs). Subjects and methods: The SQFFQ was administered to 106 (21 male and 85 female) Japanese dietitians in Aichi Prefecture in autumn, 1996 and four-season consecutive 7 day WDRs were carried out during 1996–1997. We evaluated validity of intakes of 15 foods and 31 macro- and micro-nutrients based on the SQFFQ against those according to 28 day WDRs among 79 Japanese female dietitians. Results: Mean daily intakes of selected foods and nutrients determined by the SQFFQ were generally equivalent to those measured by 28 day WDRs. Pearson's de-attenuated correlation coefficients (CCs) with log-transformation and energy-adjustment between intakes of selected foods and nutrients quantified by the SQFFQ and 28 day WDRs (minimum–median–maximum) ranged from 0.17 (beverages)–0.52 to 0.74 (rice), and Spearman's rank CCs with energy-adjustment ranged from 0.28 (confectionery)–0.42 to 0.68 (rice). Respective Pearson's CCs for intakes of nutrients were 0.28 (PUFAs)–0.51 to 0.73 (magnesium), and Spearman's rank CCs ranged from 0.23 (n-3 PUFAs)–0.45 to 0.71 (magnesium). Favorably higher agreement for intakes of foods/nutrients was achieved along with lower disagreement. Conclusions: Satisfactorily higher relative validity was attained in Japanese female dietitians with the SQFFQ. This calibrated questionnaire seems therefore appropriate for administration to Japanese dietitians to clarify associations between diet and health/disease. Sponsorship: A grant-in-aid from the Ministry of Education, Science, Sports and Culture (06454242). European Journal of Clinical Nutrition (2001) 55, 735–742

Background Lifestyle modifications are considered the most effective means of delaying or preventing the development of type 2 diabetes (T2DM). To contain the growing population of T2DM, it is critical to clarify effective and efficient settings for intervention and modalities for intervention delivery with a wide population reach. The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) is a cluster randomized controlled trial to test whether goal-focused lifestyle coaching delivered by telephone can prevent the development of T2DM in high-risk individuals in a real-world setting. This paper describes the study design and recruitment of the study subjects. Methods For the recruitment of study subjects and their follow-up annually over 3 years, we employed health checkups conducted annually at communities and worksites. Health care divisions recruited from communities and companies across Japan formed groups as a cluster randomization unit. Candidates for the study, aged 20-65 years with fasting plasma glucose (FPG) of 5.6-6.9 mmol/l, were recruited from each group using health checkups results in 2006. Goal-focused lifestyle support is delivered by healthcare providers via telephone over a one-year period. Study subjects will be followed-up for three years by annual health checkups. Primary outcome is the development of diabetes defined as FPG≥7.0 mmol/l on annual health checkup or based on self-report, which is confirmed by referring to medical cards. Results Forty-three groups (clusters), formed from 17 health care divisions, were randomly assigned to an intervention arm (22 groups) or control arm (21 clusters) between March 2007 and February 2008. A total of 2840 participants, 1336 from the intervention and 1504 from the control arm, were recruited. Consent rate was about 20%, with no difference between the intervention and control arms. There were no differences in cluster size and characteristics of cluster between the groups. There were no differences in individual characteristics between the study arms. Conclusion We have launched J-DOIT1, a nation-wide trial to prevent the development of T2DM in high-risk individuals using telephone-delivered intervention. This trial is expected to contribute to evidence-based real-world preventive practices. Trial registration UMIN000000662.

The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen.

Background A randomized control trial was performed to test whether a lifestyle intervention program, carried out in a primary healthcare setting using existing resources, can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance (IGT). The results of 3 years' intervention are summarized. Methods Through health checkups in communities and workplaces, 304 middle-aged IGT subjects with a mean body mass index (BMI) of 24.5 kg/m2 were recruited and randomized to the intervention group or control group. The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational materials provided by the study group. Results After 1 year, the intervention had significantly improved body weight (-1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control; p = 0.023) and daily non-exercise leisure time energy expenditure (25 ± 113 vs. -3 ± 98 kcal; p = 0.045). Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years. The 3-year cumulative incidence tended to be lower in the intervention group (14.8% vs.8.2%, log-rank test: p = 0.097). In a sub-analysis for the subjects with a BMI > 22.5 kg/m2, a significant reduction in the cumulative incidence was found (p = 0.027). Conclusions The present lifestyle intervention program using existing healthcare resources is beneficial in preventing diabetes in Japanese with IGT. This has important implications for primary healthcare-based diabetes prevention. Trial registration number UMIN000003136

The authors examined the effect of branched-chain amino acid (BCAA) supplementation on squat-exercise-induced delayed-onset muscle soreness (DOMS) using 12 young, healthy, untrained female participants. The experiment was conducted with a crossover double-blind design. In the morning on the exercise-session day, the participants ingested either BCAA (isoleucine:leucine:valine = 1:2.3:1.2) or dextrin at 100 mg/kg body weight before the squat exercise, which consisted of 7 sets of 20 squats/set with 3-min intervals between sets. DOMS showed a peak on Days 2 and 3 in both trials, but the level of soreness was significantly lower in the BCAA trial than in the placebo. Leg-muscle force during maximal voluntary isometric contractions was measured 2 d after exercise (Day 3), and the BCAA supplementation suppressed the muscle-force decrease (to ~80% of the value recorded under the control conditions) observed in the placebo trial. Plasma BCAA concentrations, which decreased after exercise in the placebo trial, were markedly elevated during the 2 hr postexercise in the BCAA trial. Serum myoglobin concentration was increased by exercise in the placebo but not in the BCAA trial. The concentration of plasma elastase as an index of neutrophil activation appeared to increase after the squat exercise in both trials, but the change in the elastase level was significant only in the placebo trial. These results suggest that muscle damage may be suppressed by BCAA supplementation.

The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.

To clarify sex and seasonal variations of plasma antioxidant concentrations among middle-aged Japanese.We investigated sex and seasonal variations of plasma antioxidant concentrations, including retinol, alpha-tocopherol, and carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and lycopene), in 55 middle-aged dietitians (46 women and 9 men) in Aichi Prefecture, Central Japan, who took no supplements from autumn 1996 to summer 1997. Reversed-phase high performance liquid chromatography was used to measure plasma antioxidant concentrations in overnight-fasting blood samples.Plasma levels of alpha-tocopherol, alpha-/beta-carotene, b-cryptoxanthin and lutein were significantly influenced by sex, being significantly higher for women than men in each corresponding season; retinol and lycopene, however, showed no such difference. For women, winter values of alpha-tocopherol, alpha-/beta-carotene, lutein and lycopene were significantly lower than corresponding summer values, and had reached their annual lowest. Retinol failed to show any significant seasonal variation, whereas the winter value of beta-cryptoxanthin had reached its annual highest. For men, beta-cryptoxanthin exhibited significant seasonal changes and was also highest in winter. Winter values of alpha-tocopherol, alpha-/beta-carotene and lycopene were lower compared with other seasons, but not statistically significant, probably due to the small sample size.The findings indicate that sex and seasonal variations of plasma antioxidant concentrations should be taken into account in nutritional epidemiologic studies.

Despite the lack of evidence for efficacy, an annual health examination has been advocated for the general population by the Japanese government. We conducted a cross-sectional survey to understand the attitudes of Japanese physicians toward the annual examinations.In October 2003, a questionnaire was mailed to 1971 physicians registered with Aichi Prefecture Medical Association as internists. The survey was designed to determine their opinions about the effectiveness of the periodic health examination and each of its components.The response rate was 37%. Eighty-five percent believed that a periodic health examination was effective. Nearly 80% believed that height and weight should be measured, and more than 90% supported blood pressure measurements. Nearly 70% supported a physical examination of chest and abdomen. About half believed that vision and hearing tests should be performed for all ages. More than 90% considered performing a variety of laboratory tests valuable. Three-quarters supported hepatitis B surface antigen and hepatitis C antibody determinations. Seventy to eighty percent valued the screening tests for lung, stomach, colon, breast and cervical cancer.Most Japanese primary care physicians believe that a comprehensive annual health examination as currently endorsed by public health authorities is effective.

Objectives To examine the effects of telephone-delivered lifestyle coaching on preventing the development of type 2 diabetes mellitus (T2DM) in participants with impaired fasting glucose (IFG). Design Cluster randomised trial. Setting 40 groups from 17 healthcare divisions in Japan: companies (31), communities (6) and mixed settings (3). Participants Participants aged 20–65 years with fasting plasma glucose (FPG) of 5.6–6.9 mmol/L were invited from the 17 healthcare divisions. Randomisation The groups were then randomly assigned to an intervention or a control arm by independent statisticians according to a computer-generated list. Intervention The intervention arm received a 1-year telephone-delivered intervention provided by three private lifestyle support centres (at different frequencies: low-frequency (3 times), middle-frequency (6 times) and high-frequency (10 times) support calls). The intervention and control arms both received self-help devices such as a weight scale and pedometer. Outcomes Participants were followed up using data from annual health check-ups and a questionnaire regarding lifestyle. The primary outcome was the development of T2DM defined as FPG ≥7.0 mmol/L, the diagnosis of diabetes, or use of an antidiabetic drug, confirmed by referring to medical cards. Results Of 14 473 screened individuals, participants were enrolled in either the intervention (n=1240) arm or control (n=1367) arm. Overall, the HR for the development of T2DM in the intervention arm during 5.5 years was 1.00 (95% CI 0.74 to 1.34). In the subanalysis, the HR was 0.59 (95% CI 0.42 to 0.83) in the subgroup that received phone calls the most frequently, compared with the control arm. A limitation of the study includes a lack of blinding. Conclusions High-frequency telephone-delivered lifestyle support could effectively prevent T2DM in participants with IFG in a primary healthcare setting, although low-frequency and middle-frequency phone calls did not. Trial registration number This trial has been registered with the University Hospital Medical Information Network (UMIN000000662).

BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal muscle under normal and resting conditions is in an inactive/phosphorylated state, which may contribute to muscle protein synthesis and muscle growth. Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA catabolism. Therefore, exercise may increase the BCAA requirement. It has been reported that BCAA supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. We have examined the effects of BCAA supplementation on delayed-onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in humans. The results obtained showed that BCAA supplementation prior to squat exercise decreased DOMS and muscle fatigue occurring for a few days after exercise. These findings suggest that BCAAs may be useful for muscle recovery following exercise.

We investigated the effects of progesterone and norethisterone on the apical-to-basolateral and basolateral-to-apical transports of cephalexin, a typical peptide transporter PEPT1 substrate, and the PEPT1 mRNA and protein expression levels, using the human intestinal cell line, Caco-2. Caco-2 cell monolayers (passages 50 to 60) were cultured on permeable membrane, plastic culture dish and culture tube. The Caco-2 cell monolayers were pretreated with progesterone and norethisterone (3, 10, 30 microM) for 24 h. After the pretreatment, the apical-to-basolateral and basolateral-to-apical transports of cephalexin were measured, and the densities of PEPT1 mRNA and protein expression levels were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The apical-to-basolateral transport of cephalexin was significantly decreased by the progesterone and norethisterone (30 microM each) pretreatments. By contrast, the basolateral-to-apical transport of cephalexin was not altered by the same pretreatments. The densities of PEPT1 mRNA and protein expressions were significantly decreased by progesterone and norethisterone (each at 3 and 10 microM) pretreatments compared with those of the non-treated Caco-2 cells. The results suggest that the transcription of the PEPT1 gene is downregulated by the progesterone and norethisterone pretreatments. Further studies are needed to clarify whether the inhibition of the PEPT1 gene transcription by progesterone pretreatment proceeds via sigma1-receptor or progesterone receptor.

We examined the effects of ingesting a non-sugar chocolate containing polydextrose and lactitol in place of sucrose and lactose on the concentrations of plasma glucose and serum insulin and triglyceride in humans. A regular chocolate was used as the control. A crossover study was employed, and the subjects each ingested 46 g of the control or non-sugar chocolate in the experiments. Alterations in the blood components were monitored for a period of 150 min after ingestion. The control chocolate elevated the concentrations of plasma glucose and serum insulin, with the peak occurring 30 min after ingestion, but the non-sugar chocolate had a very minor effect. The serum triglyceride concentration gradually increased after ingesting the control chocolate, but was only slightly elevated 150 min after ingesting the non-sugar chocolate. An animal study also showed an attenuated response of serum triglyceride to the administration of a fat emulsion containing polydextrose and lactitol, suggesting that the triglyceride transit through the gut was promoted by these compounds. These results suggest that, compared to regular chocolate, fat absorption in the gut was less after ingesting the non-sugar chocolate, presumably resulting in less effect on body fat deposition.

A cross-sectional study was conducted to clarify the associations of lifestyle factors (habitual exercise, alcohol intake and smoking habit) and plasma fatty acid (FA) concentrations as biomarkers of dietary FA intakes. We collected 7-d weighed diet records, lifestyle information and blood samples from 15 male and 79 female Japanese dietitians, and estimated dietary FA intakes and analyzed plasma FA concentrations. Plasma concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and (n-3) highly unsaturated FA (HUFA) derived from marine foods, but not linoleic and alpha-linolenic acid from plant origins, demonstrated positive correlations with dietary intakes (r = 0.303-0.602, P < 0.05) in both genders. Multiple linear regression analyses adjusted for age, BMI, total energy intake, fat (or respective FA) consumption and lifestyle factors showed that dietary intakes of EPA, DHA and (n-3) HUFA were positively associated with age in men (P < 0.05) and negatively associated with BMI in women [P < 0.01 for DHA and (n-3) HUFA]. The plasma concentrations of EPA, DHA and (n-3) HUFA in women were found to be positively associated with age and marine oil (or respective FA) intake (P < 0.01), and negatively associated with total energy intake [P < 0.05 for EPA and (n-3) HUFA]. Lifestyle factors were not associated with dietary FA intakes and plasma FA concentrations. These findings suggest that the plasma concentrations of EPA, DHA and (n-3) HUFA might be useful biomarkers for the assessment of relative FA intakes without considering associations with habitual exercise, alcohol intake and smoking habit.

Objective: To study seasonal variation in intake and plasma concentrations of fatty acids (FAs) in Japanese female dietitians. Subjects and methods: We assessed consumption of FAs based on four season 7 consecutive day weighed diet records from 71 Japanese female dietitians in 1996–1997. Using overnight fasting venous blood, plasma concentrations of FAs were analyzed by gas chromatography. Seasonal variation in consumption and plasma concentrations was examined by ANOVA for repeated values, followed by Tukey's multiple t-test. We calculated Spearman's partial rank correlation coefficients (CCs) between intake and plasma concentrations of FAs. Furthermore, we computed inter-seasonal Spearman's partial rank CCs for consumption and plasma concentrations of FAs. Results: Statistically significant seasonal differences were observed in consumption for most FAs, except for myristic acid, monounsaturated FAs, oleic acid, n-6 polyunsaturated FAs (PUFAs), linoleic acid, γ-linolenic acid, α-linolenic acid, PUFAs/saturated FAs, and n-6 PUFAs/n-3 PUFAs, and for most plasma concentrations, except for stearic acid, γ-linolenic acid, n-3 PUFAs, α-linolenic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and n-3 highly unsaturated FAs (HUFAs). However, statistically significant Spearman's partial rank CCs between intake and plasma concentrations were observed for EPA, DHA, n-3 HUFAs, n-6 PUFAs/n-3 PUFAs and n-6 PUFAs/n-3 HUFAs for almost all seasons. Conclusions: Seasonal variation exists in consumption and plasma concentrations of FAs, so that this should be taken into account in epidemiological analyses, including case–control and cohort studies.

To identify the serious emotional impacts as socio-psychological problems encountered by patients with late adolescent onset type 1 diabetes since their disease onset.Thirteen patients (aged 21-35 years) with type 1 diabetes, onset age from 17 to 28, were interviewed. To extract their disturbing experiences from the content of the interviews, a qualitative analysis was carried out. We categorized their experiences as socio-psychological problems.Twenty-two items of socio-psychological problems which posed obstacles to the control of diabetes were found. Problems with particularly strong impacts included a fulminant crisis prior to hospitalization; surprise and shock of patients themselves and family members upon diagnosis; unacceptable feelings against insulin injections and diabetes; difficulty and anxiety over frequent and unexpected occurrences of hypoglycemia; noncompliance with diet therapy; stress of disclosing the disease to fiancés and their parents; no understanding of or knowledge about diabetes on the part of people around them; restricted range in occupation selection, travel and daily life; existence of stigma; no place for performing insulin injections; resistant or negative feelings against disclosing to others that they had diabetes; acceptance of the disease using various emotional coping behaviors.These results suggest that for patients with such problems we should seek a more effective sort of intervention to improve their quality of life (QOL).

Objective:To study daily, weekly, seasonal, within and between-individual variance in intake of selected nutrients and minimal days necessary for assessing true intake with a specified degree of error based on four season consecutive 7 day weighed diet records (WDRs).Subjects and Methods:We evaluated consumption of energy and 30 nutrients based on four season consecutive 7 day WDRs from 80 Japanese female dietitians in 1996-1997.We examined daily, weekly, seasonal, within- and between-individual variation in nutrient intake, relative contributions of their variances to total variance, and minimal days required to estimate a person's nutrient intake within 10% and 20% of their true mean with 95% confidence intervals.Results:The relative contributions of variation for all nutrients by person were larger than those by day, week and season.Within-individual variances were greater than the between-individual variances.The ratios of within- vs.between-individual variances thus ranged from 1.3 - 26.9.Minimal days necessary for estimating nutrient consumption per person within 10% (20%) of the true mean with 95% confidence intervals ranged from 10-35 (3-9) days for energy and major nutrients and 15-640 (4-160) days for micro-nutrients.Conclusions:The relative contributions of variability by person were largest for all nutrients, followed by those due to sequence of days, season and day of week.Within-individual variation was greater than between-individual variation.Minimal days necessary for ascertaining major nutrients were in general fewer than micro-nutrients. J Epidemiol, 2002;12:85-92

Objective: To examine reproducibility of assessed intake of foods and nutrients according to a semi-quantitative food frequency questionnaire (SQFFQ) in Japanese female dietitians. Subjects and Methods: An SQFFQ was self-administered to 106 (21 male and 85 female) Japanese dietitians in Aichi prefecture in autumn 1996 and the same questionnaire was repeated in autumn 1997. Reproducibility was evaluated in terms of consumption of 15 foods and energy and 30 macro- and micro-nutrients based on the SQFFQ from 84 Japanese female dietitians. Results: For intake of foods, Pearson's correlation coefficients (CCs) with log-transformation and energy adjustment (minimum - median - maximum) ranged from 0.35 (beverages) - 0.61 - 0.71 (dairy products). ANOVA intraclass correlation coefficients (ICCs) with log-transformation and energy adjustment ranged from 0.49 (beverages) - 0.74 - 0.82 (dairy products). Spearman's rank CCs with energy adjustment ranged from 0.43 (confectionery) - 0.57 - 0.76 (dairy products). Weighted kappa statistics with energy adjustment ranged from 0.34 (confectionery) - 0.49 - 0.71 (dairy products). For consumption of nutrients, Pearson's CCs with log-transformation and energy adjustment ranged from 0.23 (zinc) - 0.55 - 0.74 (insoluble dietary fiber). ANOVA ICCs with log-transformation and energy adjustment ranged from 0.37 (zinc) - 0.70 - 0.84 (insoluble dietary fiber). Spearman's rank CCs with energy adjustment ranged from 0.25 (zinc) - 0.56 - 0.74 (magnesium). Weighted kappa statistics with energy adjustment ranged from 0.25 (zinc) - 0.50 -0.68 (insoluble dietary fiber). Conclusions: Substantially high reproducibility of consumption of foods and nutrients was attained from an SQFFQ self-administered to Japanese female dietitians.

We used low density lipoprotein (LDL) as a carrier of site-specific delivery of drugs to atherosclerotic lesions, prepared a dexamethasone palmitate (DP)-LDL complex, and examined the effect of the DP-LDL complex on foam cell formation of macrophages in vitro. LDL was isolated from human plasma and the DP-LDL complex was prepared by incubation in the presence of Celite 545. The complex contained about 50 mol of DP in 1 mol of LDL. When macrophages were incubated with LDL for 48 h, cholesterol ester was accumulated in the macrophages, indicating foam cell formation. This accumulation of cholesterol ester was significantly inhibited by incubation with the DP-LDL complex. The potency of the DP-LDL complex was similar to that of dexamethasone alone. The DP-LDL complex also significantly attenuated the accumulation of cholesterol ester induced by incubation with LDL prior to the incubation with the DP-LDL complex. These findings indicated that the DP-LDL complex showed similar characteristics to LDL, and the DP-LDL complex inhibited the foam cell formation of macrophages in in vitro experiments. This DP-LDL complex has a possibility as a drug-carrier complex for use in atherosclerosis.

Object: The association of obesity and hypertension is well recognized. However, the nature of the relationship between increased body weight and blood pressure (BP) elevation has remained obscure. Patients and Methods: We evaluated BP, insulin sensitivity, insulin clearance and fasting plasma insulin concentration in 19 younger (over 40 years) and in 15 older (more than 40 years) obese subjects to determine the relationships between BP and other factors. Insulin sensitivity and clearance were determined with the euglycemic clamp technique. Results: BP was not associated with insulin sensitivity although most of the subjects showed insulin resistance. In the younger obese group, a positive correlation between diastolic BP and body mass index (kg/m2) was found (r=0.740; p=0.043). In the older obese group, systolic and diastolic BP were correlated with fasting plasma insulin levels (r=0.705; p=0.003; r=0.574; p=0.025, respectively), and systolic BP was inversely correlated with insulin clearance (r=-0.715, p=0.003). Conclusion: These results suggest that insulin is an important factor in BP elevation in older obese subjects, but not in younger obese subjects.(Internal Medicine 38: 467-471, 1999)

A micro method for determination of indomethacin in plasma was developed. Following deproteinization of plasma with acetonitrile containing internal standard (mefenamic acid), the separation of indomethacin and internal standard was achieved by high-performance liquid chromatography using a 7 microm LiChrosorb-RP18 column (250x4 mm I.D.) at 50 degrees C. The mobile phase was 6 mM phosphoric acid-acetonitrile (50:50). The flow-rate was kept at 2.0 ml/min and the column effluent was monitored at 205 nm. The coefficients of variation of the method estimated at 0.2 and 1.0 microg/ml were 4.2 and 2.3%, and the detection limit of the drug was about 0.05 microg/ml (S/N=5). The method requires minimum pretreatment of the plasma with a small sample volume (25 microl), and is very suitable for therapeutic drug monitoring of indomethacin in premature infants with symptomatic patent ductus arteriosus.

Microallelotyping of many regions from individual colorectal tumours was used to determine the sequence and tempo of allelic loss on 5q, 17p and 18q during neoplastic progression. No allelic losses were found in normal tissues surrounding colorectal neoplasms, but losses occurred abruptly on 5q at the transition from normal colonic epithelium to the benign adenoma, and on 17p at the transition from adenoma to carcinoma, indicating an essential role for these losses in tumour progression. Allelic losses were uniform throughout extensively microdissected benign adenomas and carcinomas. However, substantial allelic heterogeneity was found in high-grade dysplasia, the transition lesion between adenoma and carcinoma. Thus, allelic losses on 5q and 17p are associated with abrupt waves of clonal neoplastic expansion, and high-grade dysplasia is characterized by a high degree of allelic heterogeneity.

The pharmacokinetics of mefenamic acid (MA), 2 mg/kg, were studied in 17 preterm infants with symptomatic patent ductus arteriosus. They were given this dosage orally at 24 h intervals. There were marked inter-individual differences in some of the pharmacokinetic parameters after the first dose; peak plasma concentration (Cmax) varied from 1.2 to 6.1 micrograms/mL with a mean of 3.8 micrograms/mL, time to reach Cmax (tmax) varied from 2 to 18 h with a mean of 7.7 h and plasma half-life (t1/2) varied from 3.8 to 43.6 h with a mean of 18.7 h. The group of infants (10/17) who had ductus closure after the first dose had significantly lower clearance (P < 0.01), longer t1/2 (P < 0.01) and higher 24 h plasma concentration (P < 0.001) compared to the group of infants (7/17) who had no ductus closure after the first dose. It appeared that the plasma concentration of MA had to be above 2.0 micrograms/mL and maintained at this concentration for at least 12 h for MA associated with ductus closure in preterm infants to take effect. In view of the inter-individual variation of plasma MA concentration and the effective plasma concentration, we suggest that measurement of the plasma concentration should be done 24 h after the first dose. This might be useful for safe and effective therapy for infants with ductus closure failure after the first dose.

Three major metabolites of mefenamic acid were isolated from the urine of a normal adult man receiving mefenamic acid orally. The structures of those metabolites were determined as glucuronides of mefenamic acid, its hydroxymethyl derivative, and its carboxylic acid derivative on the basis of spectral data.

Effect of repetitive administration of phenytoin (PHT) on the single-dose pharmacokinetics of primidone (PRM) was investigated in 3 healthy male subjects. The peak concentration of unchanged PRM was achieved at 12 and 8 h after the administration of PRM in the absence and the presence of PHT, respectively. The elimination half-life of PRM was decreased from 19.4 +/- 2.2 (mean +/- S.E.) to 10.2 +/- 5.1 h (p0.05) and the total body clearance was increased from 24.6 +/- 3.1 to 45.1 +/- 5.1 ml/h/kg (p0.01) in the presence of PHT. No significant change was observed for the apparent volume of distribution between the two treatments. In the absence of PHT, the measurable amount (or = 0.1 mumol/l) of phenobarbital (PB) and phenylethylmalonamide (PEMA) did not appear in the serum until 5.3 and 1.3 h after the PRM administration, and the peak concentrations of PB and PEMA were achieved at 52 and 36 h, but the concentrations of both metabolites were very low (PB 1.3 mumol/l; PEMA 1.7 mumol/l). In the presence of PHT, within 0.8 and 0.5 h after the administration of PRM, the derived PB and PEMA appeared in the serum. About a 6-fold increase in the peak concentrations of both the metabolites were observed (PB 8.2 mumol/l; PEMA 11.0 mumol/l). No significant changes were observed for the elimination half-lives of both PB and PEMA in the absence and presence of PHT.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Little data exist for the effectiveness of communication skills teaching for medical students in non-English speaking countries. We conducted a non-randomized controlled study to examine if a short intensive seminar for Japanese medical students had any impact on communication skills with patients. Methods Throughout the academic year 2001–2002, a total of 105 fifth-year students (18 groups of 5 to 7 students) participated, one group at a time, in a two-day, small group seminar on medical interviewing. Half way through the year, a five-station objective structured clinical examination (OSCE) was conducted for all fifth-year students. We videotaped all the students' interaction with a standardized patient in one OSCE station that was focused on communication skills. Two independent observers rated the videotapes of 50 students who had attended the seminar and 47 who had not. Sixteen core communication skills were measured. Disagreements between raters were resolved by a third observer's rating. Results There was a statistically significant difference in proportions of students who were judged as 'acceptable' in one particular skill related to understanding patient's perspectives: asking how the illness or problems affected the patient's life, (53% in the experimental group and 30% in the control group, p = .02). No differences were observed in the other 15 core communication skills, although there was a trend for improvement in the skill for asking the patient's ideas about the illness or problems (60% vs. 40%, p = .054) and one of the relationship building skills; being attentive and empathic nonverbally (87% vs. 72%, p = .064). Conclusion The results of this study suggest that a short, intensive small group seminar for Japanese medical students may have had a short-term impact on specific communication skills, pertaining to understanding patient's perspectives.

Measurement of plasma levels mefenamic acid MA by a high-performance liquid chromatographic method adapted for monitoring plasma MA in infants between sub-therapeutic and overdose levels using a small amount of plasma