Prophylactic effect of rikkunshito, an herbal medicine, for chemotherapy-induced nausea in thoracic cancer patients receiving carboplatin-based chemotherapy.

Rikkunshito has been shown to improve upper gastrointestinal symptoms and anorexia. The aim of this study was to evaluate whether rikkunshito improves chemotherapy-induced nausea in thoracic cancer patients receiving carboplatin (CBDCA)-based chemotherapy. A retrospective before-and-after comparison study was conducted in patients with thoracic cancer receiving the first cycle of CBDCA-based chemotherapy. Among 61 eligible patients, 34 received standard antiemetic therapy with a combination of 5-hydroxytryptamine-3 receptor antagonist and dexamethasone from September 2012 and June 2013 (standard group), while the other 27 received the standard antiemetic therapy plus oral rikkunshito from July 2013 and December 2014 (rikkunshito group). The rates of no nausea showed no significant difference between the standard and rikkunshito group (Overall phase: 64.7 % for standard group vs 74.1 % for rikkunshito group, p = 0.579). Subgroup analysis indicated that, in female patients, the rates of no nausea in rikkunshito groups was significantly higher than in standard group (overall phase: 44.4 % vs 100 %, p = 0.034). Rikkunshito did not demonstrate an additional prophylactic effect on standard antiemetic therapy for nausea in patients with thoracic cancer receiving CBDCA-based chemotherapy, but showed a prophylactic effect of nausea in female patients.

The recognition and incidence of peroneal tendon dislocation associated with a fracture of the talus.

AIMS: The purposes of this study were to clarify first, the incidence of peroneal tendon dislocation in patients with a fracture of the talus and second the factors associated with peroneal tendon dislocation. PATIENTS AND METHODS: We retrospectively examined 30 patients (30 ankles) with a mean age of 37.5 years, who had undergone internal fixation for a fracture of the talus. Independent examiners assessed for peroneal tendon dislocation using the pre-operative CT images. The medical records were also reviewed for the presence of peroneal tendon dislocation. The associations between the presence of dislocation with the patient characteristics or radiological findings, including age, mechanism of injury, severity of fracture, and fleck sign, were assessed using Fisher's exact tests. RESULTS: The pre-operative CT images showed peroneal tendon dislocation in eight out of 30 patients. Dislocation was found later in one patient whose pre-operative CT image had not shown dislocation. The overall incidence of peroneal tendon dislocation was 30% (9/30). The presence of dislocation was associated with the presence of a fleck sign (p = 0.03). CONCLUSIONS: Surprisingly, approximately one-third of the patients who underwent internal fixation for a fracture of the talus had peroneal tendon dislocation. This was associated with a fleck sign. Cite this article: Bone Joint J 2017;99-B:489-93.

Dielectric properties of fluorine substituted hydroxyapatite: the effect of the substitution on configuration of hydroxide ion chains.

Hydroxyapatite (HAp) [Ca5(PO4)3OH] is an extremely popular biomaterial. Moreover, HAp durability is well-known to be enhanced by fluoridation. We prepared fluoridated HAp (F-HAp; Ca5(PO4)3(OH)1-xFx) ceramics by substituting F- ions for OH- ions of HAp. F-substitution dependence of dielectric properties in F-HAp was measured to detect the configuration change of OH- ion chains. Dielectric relaxation of two kinds was observed. Each kind had a different relaxation time. Faster relaxation, which is associated with the reorientation motion of OH- ions, was only observed at the low F-substitution range (0 ≤x < 0.35). The relaxation strength decreased as the F-substitution increased. It became zero at x = 0.35, suggesting that F-substitution induces hydrogen bonds. One F- ion substituted for an OH- ion forms two hydrogen bonds with the two neighboring OH- ions and inhibits the motion of OH- ions, which results in some kind of ordered configuration in F-HAp. The configuration might be an origin that enhances the durability of the F-HAp.

Hidden osteophyte formation on plain X-ray is the predictive factor for development of knee osteoarthritis after 48 months--data from the Osteoarthritis Initiative.

OBJECTIVE: To examine whether the detection of osteophytes anywhere in the knee could serve as a pre-radiographic biomarker for osteoarthritis (OA) development. METHODS: Baseline magnetic resonance imaging (MRIs) of 132 participants in the Osteoarthritis Initiative (OAI) were studied. Based on radiographs, 66 knees were assessed as osteoarthritis-free (no-osteoarthritis [NOA], or Kellgren/Lawrence [K/L] severity grade 0/1 both at baseline and 48 months), and another 66 knees were assessed as having radiographic OA changes (pre-radiographic osteoarthritis [PROA], or with K/L grade 0/1 at baseline and grade ≥ 2 at 48 months). Using baseline MRI data, we examined eight sites of osteophyte formation: the medial and lateral femoral condyle (MFC and LFC, respectively); medial and lateral tibial plateau (MTP and LTP, respectively); medial and lateral facets of the patellofemoral joint (PM and PL, respectively); tibial spine (TS); and femoral intercondylar notch (IC). Knee joint osteophyte size was assessed via the 8-point marginal osteophytes item of the whole-organ magnetic resonance imaging score (WORMS). The frequencies and distributions of osteophytes were compared between groups. RESULTS: Mild-size osteophytes (defined as score ≥ 2) were observed more frequently at the MFC (P = 0.00278), MTP (P = 0.0046), TS (P = 0.0146), PM (P < 0.0001), PL (P = 0.0012), and IC (P < 0.0001) in PROA knees than in NOA knees. Moderate-size osteophytes (defined as score ≥ 4) were more frequently observed in PROA knees than in NOA knees only at the IC (P < 0.0001). CONCLUSION: Knees with osteophyte formation at the IC, even those of K/L severity grade 0/1, are at risk for the development of radiographic OA by 48 months.

Utility of T2 mapping and dGEMRIC for evaluation of cartilage repair after allograft chondrocyte implantation in a rabbit model.

OBJECTIVE: To investigate the effectiveness of quantitative Magnetic resonance imaging (MRI) for evaluating the quality of cartilage repair over time following allograft chondrocyte implantation using a three-dimensional scaffold for osteochondral lesions. DESIGN: Thirty knees from 15 rabbits were analyzed. An osteochondral defect (diameter, 4 mm; depth, 1 mm) was created on the patellar groove of the femur in both legs. The defects were filled with a chondrocyte-seeded scaffold in the right knee and an empty scaffold in the left knee. Five rabbits each were euthanized at 4, 8, and 12 weeks and their knees were examined via macroscopic inspection, histological and biochemical analysis, and quantitative MRI (T2 mapping and dGEMRIC) to assess the state of tissue repair following allograft chondrocyte implantation with a three-dimensional scaffold for osteochondral lesions. RESULTS: Comparatively good regenerative cartilage was observed both macroscopically and histologically. In both chondrocyte-seeded and control knees, the T2 values of repair tissues were highest at 4 weeks and showed a tendency to decrease with time. ΔR1 values of dGEMRIC also tended to decrease with time in both groups, and the mean ΔR1 was significantly lower in the CS-scaffold group than in the control group at all time points. ΔR1 = 1/r (R1post - R1pre), where r is the relaxivity of Gd-DTPA(2-), R1 = 1/T1 (longitudinal relaxation time). CONCLUSION: T2 mapping and dGEMRIC were both effective for evaluating tissue repair after allograft chondrocyte implantation. ΔR1 values of dGEMRIC represented good correlation with histologically and biochemically even at early stages after the implantation.

Preventive effects of hyaluronan from deterioration of gait parameters in surgically induced mice osteoarthritic knee model.

OBJECTIVE: Osteoarthritis (OA) leads to pain and loss of function in affected joints. Gait disturbance results from these symptoms of OA, and gait analysis can be important to evaluate the progression of OA. The purpose of this study was to analyze gait pattern in a rodent model of OA and to assess the effects of intra-articular injection of hyaluronan (IAI-HA) by gait analysis, along with histological evaluation. DESIGN: OA was induced by destabilization of the medial meniscus (DMM) of C57BL/6 mice. IAI-HA started 3 weeks after DMM surgery. Mice were allocated to three groups and were given either 800-kDa HA (800-HA), 6000-kDa HA (6000-HA) or saline. We compared these three groups with a sham group by gait analysis using CatWalk. Histological evaluation was performed to assess articular cartilage changes in the knee joints. RESULTS: Mice injected with 800-HA or 6000-HA showed gait patterns similar to that of the sham mice, while the saline-injected group showed gait disturbances 12 and 16 weeks after DMM surgery. Histological changes in articular cartilage were similar among the 800-HA, 6000-HA and saline-treated groups, demonstrating OA progression throughout the experimental time points. Positive gait-related effects of IAI-HA might occur by its pain relieving effect and/or by preventing contracture. CONCLUSION: IAI-HA prevented gait disturbances in the DMM model, but did not prevent histological changes associated with OA progression.

Antigen retrieval using sodium hydroxide for prion immunohistochemistry in bovine spongiform encephalopathy and scrapie.

Formalin-fixed and paraffin wax-embedded (FFPE) tissue sections are usually used for histopathological and immunohistochemical analyses in prion diseases in animals and man. However, formalin fixation cross-links proteins, reducing disease-associated prion protein (PrP(Sc)) immunolabelling. To detect PrP(Sc) in animals naturally affected with bovine spongiform encephalopathy (BSE) and scrapie, we applied minimal pretreatment with sodium hydroxide (NaOH). This simple pretreatment, combined with enzymatic digestion using proteinase K (PK), was equally effective in the detection of PrP(Sc) in FFPE tissue, and superior in terms of speed, compared with the usual autoclaving method. The most effective results, without any section loss, were obtained with 10 µg/ml PK in phosphate buffered saline containing 0.1% Triton-X at room temperature for 10 min and 150 mM NaOH at 60 °C for 10 min. By this simple procedure, PrP(Sc) was visualized in the brain of animals with BSE and scrapie using a range of anti-PrP primary antibodies.

Changes in hemodynamics and autonomic nervous activity in patients undergoing laparoscopic cholecystectomy: differences between the pneumoperitoneum and abdominal wall-lifting method.

BACKGROUND AND STUDY AIMS: Intraoperative changes in circulatory hemodynamics and autonomic nervous activity were evaluated in 33 patients with cholelithiasis who underwent laparoscopic cholecystectomy. PATIENTS AND METHODS: Of these patients, 18 were treated using a pneumoperitoneum (group G) and 15 using the abdominal wall-lifting method (group WL). Their ECG, blood pressure, arterial oxygen saturation, and expiratory carbon dioxide partial pressure were monitored. Autonomic nervous function was evaluated by spectral analysis of the heart rate. RESULTS: Mean blood pressure increased significantly in group G during surgery, but did not vary in group WL during any stage of surgery. The high-frequency (HF) power, an index of parasympathetic activity, decreased significantly in group G after pneumoperitoneum. However, the HF power did not decrease significantly in group WL. The LF/HF ratio, an index of sympathetic activity, increased significantly in group G after pneumoperitoneum, but did not vary in group WL. In addition, the incidence of ventricular or supraventricular arrhythmias and the severity of the arrhythmias as determined by Lown's classification were higher in group G than in group WL. These findings suggest that intraoperative changes in autonomic nervous activity, due to increased intra-abdominal pressure, were smaller in patients undergoing laparoscopic cholecystectomy using the abdominal wall-lifting method than in those undergoing laparoscopic cholecystectomy using pneumoperitoneum. The results also demonstrated that hemodynamic changes were smaller in patients undergoing the abdominal wall-lifting method than in those undergoing pneumoperitoneum. CONCLUSIONS: It was concluded that hemodynamics should be carefully monitored during pneumoperitoneum, and that the abdominal wall-lifting approach in laparoscopic cholecystectomy is a method worthy of consideration for elderly patients or those with cardiopulmonary complications.

[Theories of medicine in the newly discovered medical book "Hon'po Kagen Hishu" by San'ki Tashiro: basic prescriptions and modified prescriptions].

While investigating the formation of the Gosei-ha school in Japan by Tashiro San'ki and Manase Dosan, we discovered "Hon'po Kagen Hishu", a heretofore unknown medical book by San'ki Tashiro. A comparison of this work with Sanki's "Wakyokushu" revealed the following points. (1) "Hon'po Kagen Hishu" is a medical book compiled by San'ki Tashiro, and is believed to have been put together after the newly-compiled "Wakyokushu" (1525). (2) The book is roughly divided into two parts: basic prescriptions and modified prescriptions. "Hon'po Kagen Hishu" reveals clearly that San'ki's medical theories form the key theories of these two parts. (3) Many of the basic prescriptions contained in "Hon'po Kagen Hishu" were existing prescriptions used by the Kyokuho-ha School which was popular in Japan at the time. The modified prescriptions conform to the bian zheng pei ji (selection of drug based on the differential diagnosis) theories of the Li-Zhu medical school. (4) Among the 15 prescriptions described in the 'Shobyou Tsuyo no Yakuho' chapter of "Hon'po Kagen Hisku" secret prescriptions from schools of thought including the Nakarai school were discovered, pointing to a connection between San'ki and the Nakarai school.

Comparison of exogenous surfactant and positive end-expiratory pressure therapies in a model of human breast milk-induced acute lung injury in rabbits.

To evaluate surfactant and positive end-expiratory pressure (PEEP) as potential therapies for the acute lung injury after tracheal instillation of 0.8 ml kg-1 human breast milk (HBM) acidified to pH 1.8, adult white rabbits were anaesthetized, tracheostomized, ventilated and randomized to (six rabbits per treatment): (i) no treatment after HBM (control); (ii) exogenous Bovine surfactant (100 mg kg-1) 1 h after HBM; (iii) PEEP-pre (0.5 kPa PEEP) before and after HBM; or (iv) PEEP-post (0.5 kPa PEEP) after HBM. A fifth group of six rabbits received no tracheal instillate (no aspirate). The alveolar to arterial oxygen tension gradient (A-aDO2) and dynamic compliance were measured pre-injury and hourly for 4 h. At post-mortem, the lungs were examined histologically. A-aDO2 in all four HBM-injured groups increased to a maximum at 1 h post-injury; A-aDO2 then returned towards the baseline in the surfactant and PEEP-post groups, but remained increased in the PEEP-pre and control groups. Dynamic compliance decreased in all four HBM-injured groups. A-aDO2 and compliance were unchanged in the no aspirate group. Bronchoalveolar architecture after surfactant therapy was normal. We conclude that surfactant is a more effective therapy for HBM-induced lung injury than either 0.5 kPa PEEP-post or PEEP-pre injury.

Deficiency of a STE20/PAK family kinase LOK leads to the acceleration of LFA-1 clustering and cell adhesion of activated lymphocytes.

Lymphocyte-oriented kinase (LOK) is a member of the STE20/p21-activated kinase (PAK) family and expressed predominantly in lymphoid organs. Generation of LOK-deficient mice revealed that the leukocyte-function-associated antigen (LFA-1)/intercellular adhesion molecules (ICAM)-mediated aggregation of mitogen-stimulated T cells was greatly enhanced in the absence of LOK. Though levels of total LFA-1 and ICAMs as well as the active form of LFA-1 on T cell blasts were comparable in the presence and absence of LOK, clustering of active LFA-1 detected by binding of soluble ICAM-1 was accelerated in the absence of LOK. These results suggest that LOK is potentially involved in the regulation of LFA-1-mediated lymphocyte adhesion.

Acute lung injury after instillation of human breast milk into rabbits' lungs: effects of pH and gastric juice.

BACKGROUND: The authors compared the lung injury in rabbits that occurred after tracheal instillation of human breast milk (HBM) acidified to pH 1.8 with hydrochloric acid (HCl), HBM at its native pH (7.0), and HBM acidified with gastric juice to pH 1.8 and 3.0. METHODS: The alveolar-to-arterial oxygen tension gradient and dynamic compliance were recorded before and hourly for 4 h after intratracheal instillation of 0.8 ml/kg HBM acidified with HCI (pH 1.8), HBM at its native pH (7.0), HBM acidified with gastric juice (pH 1.8 or 3.0), or 5% dextrose solution acidified with gastric juice (pH 1.8) as a control in 30 adult rabbits. The circulating neutrophil count and phagocyte oxidant activity were determined before and 1 and 4 h after instillation. RESULTS: The alveolar-to-arterial oxygen tension gradient increased and dynamic compliance decreased significantly in all groups after instillation of HBM compared with baseline values and those in the control group. The severity of the lung injury after instillation of HBM at all pH values (1.8, 3.0, and 7.0) and after acidification with gastric juice or HCl was similar. The circulating neutrophil count increased steadily for 4 h after instillation (P < 0.013), whereas spontaneous phagocyte oxidant burst activity peaked at 1 h (P < 0.007) and returned to baseline by 4 h after instillation. CONCLUSIONS: The severity of the lung injury after tracheal instillation of 0.8 ml/kg HBM in rabbits is similar at pH values between 1.8 and 7.0 after acidification with HCl or gastric juice. Tracheal instillation of HBM increases the circulating neutrophil count and phagocyte oxidant burst activity.

Acute lung injury after tracheal instillation of acidified soya-based or Enfalac formula or human breast milk in rabbits.

PURPOSE: The aim of this study was to compare the severity of the acute lung injury after tracheal instillation of acidified soya-based or Enfalac infant formula, or human breast milk (HBM) in anesthetized rabbits. METHODS: Alveolar-arterial oxygen tension gradient (A-aDO2) and dynamic compliance were measured before (baseline) and hourly for four hours after tracheal instillation of 0.8 ml x kg(-1) soya-based or Enfalac infant formula or HBM (all acidified to pH 1.8 with hydrochloric acid) or no fluid (control) in 24 anesthetized and tracheotomized adult rabbits. The A-aDO2, the difference between alveolar and arterial oxygen tensions, was corrected for barometric pressure and carbon dioxide tension. Dynamic compliance was the ratio of the expired tidal volume to the peak inspiratory airway pressure, normalized to body weight. RESULTS: Baseline A-aDO2 and dynamic compliance were similar among the four groups. In the control rabbits, A-aDO2 remained unchanged throughout the four hours, whereas mean A-aDO2 increased 180 mm Hg in the soya-based group (P < 0.0025) and 350 and 275 mm Hg in the Enfalac and HBM groups respectively (P < 0.0002). The order of the A-aDO2 post-instillation was Enfalac approximately/= HBM > soya > control (P < 0.0002). Dynamic compliance decreased 10-12% in the control rabbits during the four post-instillation measurements compared with baseline (P < 0.033), decreased 20% in the soya-based group (P < 0.0002) and 40-50% in the Enfalac and HBM groups (P < 0.0002). CONCLUSION: The severity of the acute lung injury after intratracheal instillation of infant feeds in a volume of 0.8 ml x kg(-1) and at pH 1.8 in rabbits depends in part, on the type of feed: Enfalac approximately/= HBM > soya > control.

Medical thought of Dosan Manase's early years. (1) The meaning of the work "Toryu".

Dosan Manase was a famous Japanese doctor in the Muromachi era and was in the vanguard of the Goseiha school of Sino-Japanese traditional medicine. In his "Shinmyakukudenshu" we found an interesting account to explain the meaning of the word "Toryu", which was often found in the medical books written in Dosan's early years. This word signifies "our school" in a general sense, but in this book Dosan used it with the additional meaning of his medical thought originating in Zhu dan xi who was a famous Chinese doctor in the Yuan age. In addition, he mentioned in the same book that Toryu was introduced from China into Japan by Dodo, succeeded by Sanki and propagated by himself. Moreover our extensive investigation of other medical literature showed that Dosan, in his early years, tried to develop a system of medical thought on the basis of that of Zhu dan xi. This is worthy of note because it differs considerably from the stance adopted in Dosan's later years : while he valued Zhu dan xi, he referred to many medical books by various authors, and tried not to favour any particular school.

Brugada syndrome associated with an autonomic disorder.

A 44 year old man with Brugada syndrome and ventricular fibrillation had an autonomic disorder, shown by spectral analysis of heart rate variability and 123I-MIBG myocardial scintigraphy. Periodic variation of the ST segments was detected by Holter ECG. Increased high frequency power (0.15-0.40 Hz), an index of parasympathetic nerve activity, was observed just before ST segment elevation. In addition, local dysfunction of sympathetic nerves in the left ventricle was detected by 123I-MIBG myocardial scintigraphy. Unbalanced autonomic nerve function plays an important role in inducing Brugada-type ECG signs.

Effects of intravenous administration of L-arginine on autonomic nervous activities. Analysis of heart rate variability.

We studied the differences between isosorbide dinitrate (ISDN) and L-arginine (L-Arg), the precursor of nitric oxide, regarding autonomic nervous function by assessing changes in heart rate variability and blood levels of various vasoactive substances. Healthy volunteers received infused L-arginine (L-Arg group) or isosorbide dinitrate (ISDN group). ECGs were monitored and analyzed. Blood levels of catecholamines, endothelin, renin activity, angiotensin, human atrial natriuretic peptide, aldosterone, arginine, and citrulline were examined. Time-domain analyses of heart rate variability showed no significant changes in occurrence of R-R variability or coefficient of R-R variability, indicators of parasympathetic activity, after administration of ISDN. By contrast, both measures showed significantly more variation following administration of L-Arg. Frequency-domain analyses showed that high frequency power, an indicator of parasympathetic activity, was significantly elevated in the L-Arg group, whereas there was no significant change in the ISDN group. The blood levels of the measured vasoactive substances in L-Arg and ISDN groups were significantly different. The differences in autonomic nervous function and various kinds of vasoactive substances between the L-Arg and ISDN groups suggest that L-Arg had other actions on humoral factors in addition to vasodilation. Thus, arginine/nitric oxide may act as a neurotransmitter, altering parasympathetic nervous tension.

Coronary-pulmonary artery fistulae depicted by multiplanar reconstruction using magnetic resonance imaging.

We compared the imaging capability of magnetic resonance angiography (MRA) with that of conventional coronary angiography in a patient with coronary-pulmonary fistulae. Using the latter procedure, it is difficult to measure abnormal tortuous blood vessels in one section. However, the course of blood vessels could be evaluated quite well by rearranging serial cross-sectional MRA images using multiplanar reconstruction (MPR). This procedure allowed us to determine the anatomic positional relationship of these vessels to the peripheral cardiac great vascular system. MPR may detect sites of influx and outflow of abnormal blood vessels.