Highly conserved extracellular residues mediate interactions between pore-forming and regulatory subunits of the yeast Ca2+ channel related to the animal VGCC/NALCN family.

Yeasts and fungi generate Ca2+ signals in response to environmental stresses through Ca2+ channels essentially composed of Cch1 and Mid1. Cch1 is homologous to the pore-forming α1 subunit of animal voltage-gated Ca2+ channels (VGCCs) and sodium leak channels nonselective (NALCNs), whereas Mid1 is a membrane-associated protein similar to the regulatory α2/δ subunit of VGCCs and the regulatory subunit of NALCNs. Although the physiological roles of Cch1/Mid1 channels are known, their molecular regulation remains elusive, including subunit interactions regulating channel functionality. Herein, we identify amino acid residues involved in interactions between the pore-forming Cch1 subunit and the essential regulatory Mid1 subunit of Saccharomyces cerevisiaeIn vitro mutagenesis followed by functional assays and co-immunoprecipitation experiments reveal that three residues present in a specific extracellular loop in the repeat III region of Cch1 are required for interaction with Mid1, and that one essential Mid1 residue is required for interaction with Cch1. Importantly, these residues are necessary for Ca2+ channel activity and are highly conserved in fungal and animal counterparts. We discuss that this unique subunit interaction-based regulatory mechanism for Cch1 differs from that of VGCCs/NALCNs.

Validation of a Nomogram for Achieving Target Trough Concentration of Vancomycin: Accuracy in Patients With Augmented Renal Function.

BACKGROUND: Adjustment of initial vancomycin (VCM) dosage has been recommended on the basis of the renal function nomogram in therapeutic drug monitoring guidelines in Japan. However, this nomogram has not been clinically validated, and few studies have focused on its usefulness in patients with risk of augmented renal function. Therefore, this study aimed to evaluate the validity of the VCM nomogram and the association between patient conditions related to augmented renal function and its accuracy. METHODS: In this retrospective study, we screened data of 398 patients who received VCM and had estimated glomerular filtration rates ≥30 mL·min·1.73 m. Patients who met nomogram dosing criteria were categorized into a nomogram group, and the associations of age, renal function, and individual conditions such as febrile neutropenia, solid tumor, blood cancer, and brain injury with subtherapeutic concentrations (<10.0 mcg/mL) of VCM were evaluated. RESULTS: In total, 177 patients were categorized into the nomogram group, and 83 (47%), 81 (46%), and 13 patients (7%) had VCM trough concentrations of 10-20, <10, and >20 mcg/mL, respectively. Age <50 years was only significantly associated with subtherapeutic trough concentrations. Specific conditions of patients such as febrile neutropenia, solid tumor, and blood cancer were associated with elevated VCM clearance; however, there was no decline in trough VCM concentrations regardless of the presence of the specific conditions. CONCLUSIONS: The Japanese VCM dosing nomogram was effective in minimizing the number of instances of supratherapeutic VCM serum concentrations; however, it lacked accuracy in achieving target trough concentrations. The accuracy of the nomogram could be enhanced by categorizing patients according to age. Nevertheless, this study provides novel evidence of the usefulness of this nomogram in avoiding subtherapeutic concentrations of VCM in patients with risk factors for augmented renal clearance.

[Positive Effect of an Anesthesia Preoperative Evaluation Clinic in a Small Hospital].

BACKGROUND: We investigated the effect of an anesthetic clinic in a small hospital, with only two anesthesiologists, on operation unit activities and labor burden of the anesthesiologists. METHODS: The number of outpatients visiting the anesthetic clinic during the six month after opening of the clinic was evaluated. The doctor's fee and the number of operations under our anesthetic management were also analyzed. The total time of anesthesiologist's overtime work was compared with that of the corresponding period of the past year. RESULTS: 241 cases (48%) among 502 elective anesthesia cases were examined at the clinic, and 65% of them visited before admission for the surgery and paid for doctor's examination. Although the number of anesthesiologists working at operating rooms decreased 8% after opening of the clinic, the number of operations under the anesthetic management increased 6% compared to the corresponding period of the past year. The overtime work of anesthesiologists decreased drastically probably due to increased efficiency of the operative anesthetic labor resulting from the reduction of anesthesiologist's preoperative duties at bedside. CONCLUSIONS: Establishment of an anesthetic clinic had a positive effect on both hospital-management and anesthesiologist-labor even in a small hospital with a few anesthesiologists.

Copper- and Silver-Catalyzed Diastereo- and Enantioselective Conjugate Addition Reaction of 1-Pyrroline Esters to Nitroalkenes: Diastereoselectivity Switch by Chiral Metal Complexes.

syn-Diastereoselective conjugate addition of 1-pyrroline esters to nitroalkenes in good yields with an excellent enantioselectivity by using CuOAc/Me-FcPHOX catalyst in the presence of pyridine. In contrast, AgOAc/tBu-ThioClickFerrophos catalyzed the anti diastereoselective conjugate addition with a high enantioselectivity without additional base. Thus, the preparation of chiral 1-pyrroline derivatives bearing diverse stereochemistry could be achieved. The diastereoselective reduction of the imine group in the conjugate adduct could afford the 2,5-cis-proline ester derivative.

Changes in compliance with Japanese antiemetic guideline for chemotherapy-induced nausea and vomiting: a nationwide survey using a distributed research network.

OBJECTIVE: Prophylaxis of chemotherapy (CT)-induced nausea and vomiting (CINV) is important for patient's quality of life and adherence to CT. Neurokinin receptor antagonist (NK1 antagonist) was marketed in Japan in December 2009 and the first guideline for antiemetics for CINV was released in May 2010 from Japan Society of Clinical Oncology (JSCO). We assessed changes in compliance with the JSCO guideline during the first 18 months from the launch of NK1 antagonist in Japan. METHODS: Patient-level data was extracted locally using a nationwide distributed research network consisting of 39 hospitals. Monthly compliance rates for acute (day of CT) and delayed (days 2-5) phases were summarized according to the emetic risks. RESULTS: In total, 81,739 CTs for 9,978 patients were analyzed. Prescription of oral NK1 antagonist was started in 31/39 hospitals during the study period. The compliance in acute phase for high emetic risk (HER) CTs gradually improved up to 39.3% whereas it reached only to 10-15% in delayed phase. The extra use of antiemetics decreased inversely to the increased compliance. Better compliance for HER CTs was associated with opioid use, younger age, second or later cycles, and CT regimens. Compliance in acute phase was better in inpatient whereas that in delayed phase was better in outpatients. CONCLUSIONS: A multi-hospital survey revealed that more than half of the HER CTs remained without accompanying the standard antiemetic therapies. Association with the compliance and CINV outcomes would be also interesting to explore.

Subcutaneous administration of sodium alginate oligosaccharides prevents salt-induced hypertension in Dahl salt-sensitive rats.

OBJECTIVE: We investigated the mechanism of antihypertensive effects of sodium alginate oligosaccharides, which are enzymatic products of high-molecular-weight natural alginate from seaweeds, in Dahl salt-sensitive (Dahl S) rats. MATERIALS AND METHODS: Dahl S rats fed a high-salt (4% NaCl) diet were subcutaneously administered sodium alginate oligosaccharides (60 mg/day using a continuous osmotic mini-pump) for 14 days. Systolic blood pressure (SBP) was measured using the tail-cuff method, and we determined the influence of the alginate treatment on the metabolism of sodium by measuring sodium excretions in the feces and urine. RESULTS: SBP increased in an age-dependent manner in the untreated Dahl S rats. Sodium alginate oligosaccharide treatment via the subcutaneous route almost completely abolished salt-induced hypertension in Dahl S rats fed a high-salt diet. The level of fecal or urinary sodium excretion did not significantly change during the treatment period with the alginate oligosaccharides. The reduction in SBP rapidly recovered after cessation of the treatment. Moreover, the level of urinary protein excretion was lower in the treated Dahl S rats than in the untreated rats during the experimental period. CONCLUSIONS: Our results suggest that sodium alginate oligosaccharides attenuate salt-induced hypertension in Dahl S rats not through reducing salt absorption, but probably through a direct action on vascular vessels.

Polymorphisms of the UDP-glucuronosyl transferase 1A genes are associated with adverse events in cancer patients receiving irinotecan-based chemotherapy.

A prodrug, irinotecan (CPT-11), is a semisynthetic derivative of camptothecin. It inhibits topoisomerase I and is used for treatment of lung, stomach, and colon cancers in Japan. The active form of CPT-11, SN-38, causes the adverse events such as neutropenia and diarrhea. Since SN-38 is metabolized to non-toxic SN-38-glucuronide by hepatic uridine diphosphate glucuronosyl transferase (UGT) 1A enzymes, UGT1A enzyme activities may influence adverse events of CPT-11. UGT1A enzymes consist of three isozymes (1A1, 1A7, 1A9), and their genes are characterized by polymorphisms. Here, to identify the genetic factors that affect the adverse events of CPT-11, we determined the polymorphism in three UGT 1A isozyme genes in 45 inpatients with lung, colon, or stomach cancer. The univariate and multivariate analysis of patients' physiological and genetic factors revealed that one or more genotypes of UGT1A1*6/*28, UGT1A7*3/*3, and UGT1A9*1/*1 may enhance the adverse events. Each of the first two genotypes is expected to generate the enzyme with low catalytic activity. The UGT1A9*1 represents the wild-type allele, which however provides the lower catalytic activity, compared to the UGT1A9*22 variant that is common in this study population. Indeed, four (67%) out of six patients who carry one or more of the above-mentioned genotypes suffered from adverse events, leading to the discontinuation of chemotherapy or the decreased dose of CPT-11. By contrast, only six (15%) out of 39 patients with other genotypes suffered from adverse events. In conclusion, UGT1A1*6/*28, UGT1A7*3/*3, and UGT1A9*1/*1 should be taken into consideration as markers for preventing severe adverse events of CPT-11 administration.

Individual experiences and issues in predictive genetic testing for untreatable hereditary neuromuscular diseases in Japan.

Predictive genetic testing (PT) for hereditary diseases that do not have effective treatment or prevention strategies places a psychological burden on parties and their families. There has been little research on the psychosocial aspects of PT in Japan, nor are there any guidelines. To address this gap, we conducted a questionnaire survey of parties at genetic risk for untreatable hereditary neuromuscular diseases, and the National Liaison Conference of Genetic Medicine Departments (GMDs). Of the 63 parties who responded to the survey, 10 (15.9%) had undergone PT. Of the 67 GMDs, only 18 facilities (26.9%) were conducting PT with written procedures. At least two of the six parties with such results felt that some follow-up would be helpful. One party had taken PT for preimplantation genetic testing for monogenic (PGT-M); four, who had no experience, provided free text responses indicating that PGT-M or prenatal genetic testing was chosen as a motivation. Eight were unaware of PT, and six were unaware of their blood relatives' diseases being "hereditary." The results highlighted the need to: 1) develop guidelines for PT in untreatable hereditary diseases; 2) provide access to PT information; and 3) share the "heritability" of diseases with family and relatives.

[Feasibility study of locomotion training in a home-visit preventive care program].

AIM: To evaluate the feasibility of locomotion training (single-leg standing and squats) in a home-visit preventive care program for the elderly. METHODS: We invited 246 people who were not attending any preventive care programs within the long-term care insurance system. Among these, 60 participated in the current program. We administered a hearing survey, measured the single-leg stance time with eyes open, and subjects underwent locomotion training. Each participant was asked to repeat 1 set of training exercises 3 times per day at home. One set consists of standing on each leg for 1 minute and squatting 5 to 6 times. We telephoned the participants regularly during the 3 month program (locomo call). At the end of the program, we visited the participants and measured the single-leg stance time with eyes open. RESULTS: A total of 60 elderly adults participated in the program (15 men, 45 women). Among subjects secondary prevention of musculoskeletal (n=313), 67 were participating in site-visit preventive care programs conducted by the local authorities (21.4%). Among these 313, 127 were participating in site-visit preventive care programs or locomotion training (40.6%). It shows the increasing of the participation rate 21.4% to 40.6%. The continuance rate was 91.7%. The single-leg stance time improved for both men (16.2±17.7 sec, p<0.05) and women (57.2±79.7 sec, p<0.01) compared to the baseline. Similarly, improvement was observed in the single-leg stance time for both the young-old (62.2±67.9 sec, p<0.01) and the old-old (39.2±73.8 sec, p<0.01). CONCLUSIONS: We consider that the locomotion training program which we introduced in the current home-visit preventive care program was effective and highly feasible for the elderly who have not previously responded conventional site-visit preventive care programs.

Molecular, functional, and histopathological classification of the pituitary neuroendocrine neoplasms.

In 2017, WHO published an updated classification of the pituitary adenomas according to the lineages defined by the transcription factors, PIT1, SF1 and TPIT. Nomenclature of the pituitary tumors follows the mature cell types such as somatotroph (GH), lactotroph (LH), thyrotroph, corticotroph, and gonadotroph (FSH, LH). Null cell adenomas are defined by the absence of expression of any hormones and transcription factors. Not infrequently, the pituitary adenomas are invasive to the adjacent structures and are designated as aggressive adenomas. Knosp grading is often used to define the aggressiveness of the tumor. Sparsely granulated somatotroph adenomas and Crooke cell corticotroph adenomas are representative aggressive adenomas. Recently, genomics regarding various adenomas have been clarified, such as GNAS for somatotrophs and USP8 for corticotrophs. Familial pituitary adenomas are another aspect which has been clarified such as MEN1, Carney's complex, familial isolated pituitary adenoma and McCune-Albright syndrome. The pituitary adenomas often produce GH or PRL, hormones of PIT1 transcription factor. It has been agreed that the pituitary adenomas share the characteristics of neuroendocrine neoplasms. The terminology of pituitary neuroendocrine tumor has been discussed. This review article covers various aspects of pituitary adenomas.

A retrospective study comparing interventions by oncology and non-oncology pharmacists in outpatient chemotherapy.

BACKGROUND: The differences in the clinical pharmacy services (CPS) provided by oncology and non-oncology pharmacists have not been sufficiently explained. AIM: This study aimed to demonstrate the differences in direct CPS provided by oncology and non-oncology pharmacists for patients and physicians, and to assess the potential impact of these services on medical costs. METHODS: We retrospectively examined CPS provided by oncology and non-oncology pharmacists for outpatients who underwent chemotherapy between January and December 2016. RESULTS: In total, 1177 and 1050 CPS provided by oncology and non-oncology pharmacists, respectively, were investigated. The rates of interventions performed by oncology and non-oncology pharmacists for physicians-determined treatment were 18.5% and 11.3%, respectively (p < .001). The rates of oncology and non-oncology pharmacist interventions accepted by physicians were 84.6 and 78.8%, respectively (p = .12). Level 4 and Level 5 interventions accounted for 64.6% of all oncology pharmacist interventions and 53.0% of all non-oncology pharmacist interventions (p = .03). The rates of improvement in symptoms from adverse drug reactions among patients resulting from interventions by oncology and non-oncology pharmacists were 89.4 and 72.1%, respectively (p = .02). Conservative assessments of medical cost impact showed that a single intervention by an oncology and by a non-oncology pharmacist saved ¥6355 and ¥3604, respectively. CONCLUSION: The results of the present study suggested that CPS by oncology pharmacists enable safer and more effective therapy for patients with cancer and indirectly contribute to reducing health care fees.

Association of dry skin with intercellular lipid composition of stratum corneum after erlotinib administration.

PURPOSE: Erlotinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, causes skin disorders such as dry skin, which impairs the skin barrier function. Stratum corneum (SC) lipids play an important role in skin barrier function; therefore, this study aimed to investigate the relationship between erlotinib-related dry skin and changes in the intercellular lipid composition and structure of the SC. METHODS: Overall, 21 patients with non-small lung cancer were enrolled in this study. All patients received 150 mg/day erlotinib orally. A SC sample of each patient was collected from the inner forearm using the tape stripping method on days 0, 7, 14, 28, and 56 after erlotinib administration. The intercellular lipid components of ceramide (CER), free fatty acid (FFA), and cholesterol sulfate (CS) in samples extracted from the tape were analyzed using liquid chromatography/time-of-flight/mass spectrometry. SC samples from six healthy subjects were collected as controls on days 0, 28 and 56 and analyzed similarly. RESULTS: Although total CER and FFA levels were not changed after erlotinib administration, the levels of CER subclasses [AP] and [AH] and hydroxy FFA, which are structural components of CER subclass [A], decreased. In contrast, the CS levels increased after erlotinib administration. Moreover, higher CS levels in the SC correlated with the clinical condition of dry skin. No changes were observed in the SC lipid composition in healthy subjects. CONCLUSION: Erlotinib-related dry skin was associated with a higher CS level in the SC.

Effects of repeated morphine treatment on the antinociceptive effects, intestinal absorption, and efflux from intestinal epithelial cells of morphine.

The present study was conducted to investigate the effects of repeated treatment with morphine on the drug's antinociceptive effects, intestinal absorption, and transepithelial transport. The antinociceptive effects of morphine in rats were markedly decreased after repeated oral administration of the drug for 5 d, indicating the development of tolerance. In the morphine-tolerant rats, intestinal absorption of morphine was determined using the in situ loop method. Absorption of morphine from the jejunum was significantly decreased after repeated administration. The permeability of human intestinal epithelial Caco-2 cells was increased in the efflux direction after repeated treatment. The repeated administration of morphine also reduced the cellular accumulation and efflux of P-glycoprotein substrates ([(3)H]vincristine and rhodamine123) from Caco-2 cells, suggesting that it enhances P-glycoprotein-mediated efflux in Caco-2 cells. These results suggest that repeated use enhances the efflux of morphine in the epithelial cells of the small intestine, subsequently decreasing its intestinal absorption.

Serum cystatin C as a better marker of vancomycin clearance than serum creatinine in elderly patients.

OBJECTIVES: The purpose of this study is to assess the usefulness of the concentration of cystatin C (Cys-C) in serum for predicting the clearance of vancomycin (CLvcm) compared with the serum concentration of creatinine (SCr) in the elderly. METHODS: Thirty-nine serum samples were obtained from 24 elderly patients (65 years and older). Creatinine clearance (CLcr) and the glomerular filtration rate calculated from the concentration of Cys-C (GFRcys-c) were estimated using Cockcroft & Gault's formula and Larsson's formula, respectively. RESULTS: The correlation constant for CLvcm and the reciprocal of Cys-C (p=0.883) was significantly higher than that for CLvcm and the reciprocal of SCr (p=0.575, p<0.005). GFRcys-c was strongly correlated with CLvcm (p=0.883) and the constant was significantly higher than that for the correlation between CLvcm and CLcr (p=0.684, p<0.05). These results suggest that the serum concentration of Cys-C is a more reliable marker for predicting CLvcm than is SCr in elderly patients.

Different effects of morphine and morphine-6beta-glucuronide on formalin-evoked spinal glutamate release in conscious and freely moving rats.

The aim of this study was to investigate comparatively the role of spinal glutamate in the antinociceptive effect of morphine and morphine-6beta-glucuronide (M6G). The glutamate concentration in the spinal microdialysates and flinching behavior were simultaneously measured in conscious and freely moving rats after the intraplanter injection of formalin. The subcutaneous administration of morphine (0.3-3mg/kg) in these rats suppressed dose dependently both flinching behavior and spinal glutamate release induced by formalin. Similarly, the subcutaneous administration of M6G at doses of 0.1-3mg/kg suppressed the formalin-induced flinching behavior in the dose-dependent manner, but it did not cause a dose-related inhibition of spinal glutamate release. The inhibitory effects of morphine on the formalin-induced flinching behavior and spinal glutamate release were markedly attenuated by repeated treatment with this drug for 5 days in rats. Thus, there was a significant (P<0.05) correlation between antinociception and inhibitory effect on glutamate release of morphine in rats. These results suggest a significant difference between morphine and M6G in the participation of spinal glutamate for the antinociceptive effect.

Comparative measurement of spinal CSF microdialysate concentrations and concomitant antinociception of morphine and morphine-6beta-glucuronide in rats.

Morphine-6beta-glucuronide (M6G) is well known as a potent active metabolite in humans. To clarify concentration-antinociceptive effect relationships for morphine and M6G, we evaluated comparatively the pharmacokinetics and antinociceptive effects of morphine and M6G. The spinal CSF concentration and antinociception were simultaneously measured by using the combination of a microdialysis method and the formalin test in conscious rats after the s.c. administration of morphine (0.3-3 mg/kg) and M6G (0.1-3 mg/kg). The plasma concentration of M6G after s.c. administration was higher than that of morphine, as shown by the 2.1 times greater value of area under the concentration-time curve (AUC(plasma)). The spinal CSF concentrations of morphine and M6G increased dose-dependently. The AUC(CSF) of M6G was 1.6-1.8 times higher than that of morphine at each dose. Administration of morphine and M6G dose-dependently suppressed the flinching behavior induced by formalin injection. The ED(50) values for M6G were 3 times lower than those of morphine, although the spinal CSF concentration versus antinociceptive effect curves of morphine and M6G were very similar, with similar EC(50) values. These results suggest that the antinociceptive potencies of morphine and M6G, evaluated by simultaneous measurements of spinal CSF drug concentration and antinociception, are equivalent. Simultaneous measurement of spinal CSF concentration and antinociception by using microdialysis should be useful for elucidating the relationship between pharmacokinetics and pharmacodynamics of various opioids.

[A study to establish screening standards for determining cases for follow-up on health check-ups at 4 months, 18 months and 3 years of age from the viewpoint of child-rearing support].

OBJECTIVE: For maternal and child health, in addition to assistance to children, support to guardians is needed with the change in the social environment due to child-rearing. In Kobe city, from 2002/ 04/01, interview sheets for health check-ups at 4 months, 18 months and 3 years of age were revised and questions about child-rearing were added. The purpose of the present study was to clarify revisions to interview sheets regarding childcare support. METHODS: A total of 3,308 cases of mothers and children who underwent their health check-ups between 2002/04/01 and 2002/12/31 were surveyed, and the replies in the interview sheets were analyzed using the chi-square test for independence and the Pearson's correlation coefficient. RESULTS: In addition to children's development, factors for child-rearing in the home, including cooperation from the father, are of great importance. Moreover, subjectivity about mother's child-rearing is influenced by the support of child-rearing friends. CONCLUSIONS: Public health nurses should use not only the replies in interview sheets but also the appearance of guardians at health check-ups as important factors for screening. Further consideration of the influence of each question for evaluation is necessary to establish screening standards.

Dietary Intake in Body Mass Index Differences in Community-Based Japanese Patients with Schizophrenia.

BACKGROUND: Patients with schizophrenia reportedly have a high prevalence of obesity. One of the reasons is a poor choice of diet. The goal of this study was to clarify characteristics of the dietary intake across the strata of the body mass index (BMI) and to compare the general population and patients with schizophrenia in Japan. METHODS: This is a cross-sectional study of 51 patients with schizophrenia residing in rural areas in 2011. Anthropometric indices (of height, weight, body mass index) were measured at the commencement of the survey. Intakes of energy, protein, fat, carbohydrate, calcium, phosphorus, vitamins, total fiber, and salt were noted through a 3-day dietary recording. The nutrient intake was estimated using Excel add-in software (Excel Eiyou-kun Ver. 6.0, Kenpakusha Co., Ltd.). Patients were divided into two groups: those with a BMI ≥25 kg/m(2) and with a BMI <25 kg/m(2), and the differences in their nutrition intake were analyzed. To compare these patients with the general population, the results of the National Health and Nutrition Survey, 2010 (NHNS) were used (the NHNS group). For statistical analysis, an unpaired t-test was performed with P < 0.05. RESULTS: Patients with a BMI ≥25 kg/m(2) had the higher intakes than those with a BMI <25 kg/m(2) of energy, fat and phosphorus and salt. Patients with schizophrenia showed higher intakes of energy, carbohydrate, fat, calcium, phosphorus and salt than the NHNS group. CONCLUSION: The characteristics of the dietary intake in patients with schizophrenia were suggested the food constitution that is likely to increase the body weight.

Community-based exercise program reduces chronic knee pain in elderly Japanese women at high risk of requiring long-term care: a non-randomized controlled trial.

AIM: To estimate the prevalence of low back pain and/or knee pain among the elderly at high risk of requiring long-term care, and to determine the effectiveness of a community-based exercise program provided in accordance with the Motor Function Improvement Program for improving low back and/or knee pain. METHODS: The target population of this study was 320 residents aged ≥65 years who were eligible for the exercise program. For the intervention group, weekly exercise classes of 120 min duration were held 12 times over 3 months. The main outcome measures were changes between the baseline and 3-month follow up in visual analog scale (VAS) scores for pain and in the Western Ontario McMaster Osteoarthritis Index (WOMAC) pain for severity of knee pain. RESULTS: The number of participants reporting chronic low back and/or knee pain was 252 with a prevalence of 78.8%. Among them, 68 who were allocated to the intervention group and 125 to the control group completed the study, and were stratified by sex. In women, change in the VAS scores of low back pain was -17.5±23.2 for the intervention group and -7.2±23.4 for the control group (between-group differences P=0.03). For knee pain, significant changes in the VAS scores (between-group differences P=0.04) and WOMAC pain (P<0.001) were observed; -14.9±24.9 and -0.6±3.1 for the intervention group, and -0.2±28.5 and 2.2±3.2 for the control group, respectively. No significant difference was observed in men. CONCLUSION: Community-based exercise programs might reduce prevalent knee pain in elderly women at high risk of requiring long-term care.

Influence of the slow infusion of a soybean oil emulsion on plasma cytokines and ex vivo T cell proliferation after an esophagectomy.

BACKGROUND: Lipid emulsions have been suggested to reduce immune responses, particularly in severely stressed patients. The authors investigated the influence of the slow intravenous infusion of a soybean oil-based lipid emulsion on some immune parameters in patients who had undergone an esophagectomy for esophageal cancer. METHODS: Thirty-two patients who had undergone an esophagectomy were randomly divided into a lipid emulsion (LPD)-treated group and a control group. All patients received parenteral feeding with a glucose-based solution. Patients in the LPD group received 100 mL of a 20% soybean oil emulsion for 7 days after the esophagectomy in addition to the glucose-based feeding. A slow infusion rate (0.09-0.12 g/kg/h) was adopted to take account of the intrinsic degradation of infused lipids. Immune responses were measured based on lymphocyte proliferation and serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The authors also measured levels of rapid turnover proteins (ie, transferrin, prealbumin, and retinol-binding protein). RESULTS: Phytohemagglutinin- and concanavalin A-stimulated lymphocyte proliferation significantly decreased after the esophagectomy, but no significant difference was seen between the LPD and control groups. No significant difference in changes in plasma concentrations of MCP-1, IL-6 and TNF-α occurred between the 2 groups either. Plasma concentrations of rapid turnover proteins did not differ between the groups. CONCLUSIONS: These results indicate that the lipid emulsion did not affect the immune parameters measured in patients who had undergone an esophagectomy when administered at a slow rate.