Comparison of pharmacokinetics of intragastrically and intrarectally administered levetiracetam tablets in healthy non-epileptic dogs.

Canine status epilepticus (CSE) is characterized by epileptic seizures that are longer than 5 min or more than one seizure with incomplete recovery. Currently, diazepam suppositories are generally prescribed for CSE. Levetiracetam (LEV) is one of the newest antiepileptic drugs currently available. This study compared the pharmacokinetics of intragastric and intrarectal administration in oral formula of LEV in four healthy beagles as a reference data when the owner administers levetiracetam to dogs by himself at home. Blood for measuring plasma LEV concen- trations was collected 0, 30, 60, 90, 120, 240, 360, and 540 min after LEV administration. The time to reach the maximum plasma concentration (Tmax) was markedly shorter with intra- rectal administration (45±26 min) than with intragastric administration (270±99 min). Intrarectal administration of LEV tablets could be an effective option for treating canine seizures although it might be a limit for treating CSE because the absorption rate is not fast enough.

Von Willebrand Factor Deposition and ADAMTS-13 Consumption in Allograft Tissue of Thrombotic Microangiopathy-like Disorder After Living Donor Liver Transplantation: A Case Report.

BACKGROUND: Thrombotic microangiopathy (TMA) pathogenesis after living donor liver transplantation (LDLT) is thought to be caused by release of unusually large von Willebrand factor multimers (UL-vWFMs) resulting from sinusoidal endothelial cell damage and induction of platelet adhesion and aggregation. A decrease in a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs-13 (ADAMTS-13) that cleave UL-vWFMs might cause excessive UL-vWFMs activity and result in platelet thrombus formation. However, this phenomenon has not undergone a full pathologic assessment. PROCEDURES: A 60-year-old man was diagnosed with hepatitis C-related end-stage cirrhosis. His son was the donor, and he underwent LDLT. On postoperative day 44, his laboratory findings met most TMA diagnostic criteria, and he was diagnosed with TMA-like disorder (TMALD). Localization of CD42b as a platelet marker, vWF, and ADAMTS-13 in allograft tissue of this patient were evaluated using immunohistochemistry. RESULTS: CD42b expression was observed as platelet aggregates attached to hepatocytes or within the hepatocyte cytoplasm, a morphology called extravasated platelet aggregation (EPA). vWF expression was observed mainly as deposited compact clusters, and ADAMTS-13 expression resembled distinct dots throughout the liver tissue. CONCLUSION: These findings suggest that EPA indicated sinusoidal endothelial cell damage followed by detachment, and vWF deposition resulted from UL-vWFM oversynthesis. ADAMTS-13 might be consumed in the allograft tissue to cleave UL-vWFMs, but ADAMTS-13 levels might be insufficient to cleave all the deposited UL-vWFMs. We present the case of an LDLT recipient diagnosed with TMALD using blood tests, which showed the presence of TMA pathogenesis in the allograft.

Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation.

BACKGROUND: The exact sequence of events leading to ultimate hepatocellular damage following ischemia/reperfusion (I/R) is incompletely understood. In this article, we review a mechanism of organ dysfunction after hepatic I/R or immunosuppressive treatment, in addition to the potential of liver sinusoidal endothelial cell (LSEC) protection and antiplatelet treatment for the suppression of hepatocellular damage. METHODS: A review of the literature, utilizing PubMed-NCBI, was used to provide information on the components necessary for the development of hepatocellular damage following I/R. RESULTS: It is well-established that LSECs damage following hepatic I/R or immunosuppressive treatment followed by extravasated platelet aggregation (EPA) is the root cause of organ dysfunction in liver transplantation. We have classified three phases, from LSECs damage to organ dysfunction, utilizing the predicted pathogenic mechanism of sinusoidal obstruction syndrome. The first phase is detachment of LSECs and sinusoidal wall destruction after LSECs injury by hepatic I/R or immunosuppressive treatment. The second phase is EPA, accomplished by sinusoidal wall destruction. The various growth factors, including thromboxane A2, serotonin, transforming growth factor-beta and plasminogen activator inhibitor-1, released by EPA in the Disse's space of zone three, induce portal hypertension and the progression of hepatic fibrosis. The third phase is organ dysfunction following portal hypertension, hepatic fibrosis, and suppressed liver regeneration through various growth factors secreted by EPA. CONCLUSION: We suggest that EPA in the space of Disse, initiated by LSECs damage due to hepatic I/R or immunosuppressive treatment, and activated platelets may primarily contribute to liver damage in liver transplantation. Endothelial protective therapy or antiplatelet treatment may be useful in the treatment of hepatic I/R following EPA.

Efficacy of conversion gastrectomy following docetaxel, cisplatin, and S-1 therapy in potentially resectable stage IV gastric cancer.

BACKGROUND: Recent advances in gastric cancer chemotherapy have made macroscopic complete resection possible in some patients with stage IV disease. METHODS: We retrospectively investigated the efficacy of multimodal therapy with combined docetaxel, cisplatin, and S-1 (DCS) and conversion gastrectomy in 57 patients with stage IV gastric cancer. RESULTS: Of the 57 patients, 15 patients were categorized into potentially resectable case, which is defined as patients with single incurable factor including the upper abdominal para-aortic lymph node metastasis (16a2b1 PAN metastasis) or fewer than three peripheral liver metastases. The other 42 were categorized as initially unresectable. All of patients underwent DCS therapy, and then 34 patients underwent conversion gastrectomy. The 3-year overall survival (OS) rate among the patients who underwent conversion gastrectomy was 50.1% with MST of 29.9 months. They had significantly longer OS than patients who underwent DCS therapy alone (p < 0.01). Univariate analysis among the patents with conversion gastrectomy identified 16a2b1PAN metastasis, peritoneal metastasis, potential resectable case, R0 resection as significant prognostic factors. A 3-year OS in potential resectable cases was 92.9%. Multivariate analysis identified potential resectability as the only independent prognostic factor contributing to OS (HR 0.133, 95%CI 0.024-0. 744, p = 0.021). In contrast, clinical response was selected as the only independent prognostic factor in the subgroup of initially unresectable cases (HR 0.354, 95%CI 0.151-0.783, p = 0.021). CONCLUSION: Patients with potentially resectable disease had a remarkably good prognosis among stage IV gastric cancer patients, and might be ideal candidates for conversion gastrectomy following DCS therapy.

The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells.

Several common biological properties between cancer cells and embryonic stem (ES) cells suggest the possibility that some genes expressed in ES cells might have important roles in cancer cell growth. The transcription factor ZFP57 is expressed in self-renewing ES cells and its expression level decreases during ES cell differentiation. This study showed that ZFP57 is involved in the anchorage-independent growth of human fibrosarcoma HT1080 cells in soft agar. ZFP57 overexpression enhanced, whereas knockdown suppressed, HT1080 tumor formation in nude mice. Furthermore, ZFP57 regulates the expression of insulin-like growth factor 2 (IGF2), which has a critical role in ZFP57-induced anchorage-independent growth. ZFP57 also promotes anchorage-independent growth in ES cells and immortal fibroblasts. Finally, immunohistochemical analysis revealed that ZFP57 is overexpressed in human cancer clinical specimens. Taken together, these results suggest that the ES-specific transcription factor ZFP57 is a novel oncogene.

Severe veno-occlusive disease/sinusoidal obstruction syndrome after deceased-donor and living-donor liver transplantation.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) occurring after liver transplantation is a relatively rare complication but it often takes a life-threatening course. However, the detailed etiology and mechanism of VOD/SOS after liver transplantation (LT) remains unclear. We report two cases with rapidly progressive VOD/SOS after ABO-identical LT resistant to various therapies. In case 1, in which the patient underwent deceased-donor LT, the first episode of acute allograft rejection was triggered VOD/SOS, and the presence of donor non-specific anti-HLA antibodies was confirmed. The recipient died with graft failure on day 46 after transplantation. Case 2, in which the patient underwent living-donor LT from the mother, had neither rejection nor mechanical venous obstruction, but condition of the patient rapidly worsened and he died on day 13 after transplantation. This recipient's direct cross-match test for the donor's B lymphocyte was strongly positive, but that for T lymphocyte was negative. In both cases, neither stenosis of hepatic vein outflow tract nor C4d deposition in post-transplantation liver biopsy specimens and autopsy specimen was found. On the other hand, in both cases, the patient was transfusion unresponsive thrombocytopenia and hyperbilirubinemia persisted postoperatively, and glycoprotein Ⅰ bα was strongly stained in the neighboring centrilobular area (zone 3), especially in the space of Disse, and platelet phagocytosis was observed in Kupffer cells and hepatocytes around zone 3 such as clinical xenotransplantation of the liver in post-transplantation liver biopsy specimens. From the viewpoint of graft injury, VOD/SOS was considered that sustained sinusoidal endothelial cells injury resulted in bleeding in the space of Disse and led to around centrilobular hemorrhagic necrosis, and the fundamental cause was damage around centrilobular area including sinusoid by acute cellular rejection, antibody-mediated rejection or ischemic reperfusion injury. The extrasinusoidal platelet activation, aggregation, and phagocytosis of platelets were some of the main reasons for VOD/SOS and transfusion-resistant thrombocytopenia.

Relationship between midgut malrotation and anatomy of the hepatoduodenal ligament: a rare anatomical variation in a deceased donor.

INTRODUCTION: Anatomical variations around the hepatoduodenal ligament greatly influence surgical procedures and the difficulty of operations. Here, we report the case of a deceased donor with midgut malrotation (MgM) and anatomical variation. We also present an anatomical comparison between MgM and normal cases. CASE REPORT: The donor, a male in his 60s, was diagnosed with MgM based on preoperative computed tomography. Intraoperatively, the liver graft was harvested from the proper hepatic artery (PHA), but its length was too short for reconstruction. Therefore, the hepatic artery was reconstructed at both the left and right hepatic arteries. METHODS: The length of the proper hepatic artery (l-PHA) and main trunk of the portal vein (l-PV) was compared between MgM and control groups (n = 9) using computed tomography. The ratio of PHA (r-PHA) and PV (r-PV), which was calculated as the l-PHA or l-PV divided by the patient's height, was also compared. RESULTS: The r-PV was 1.3% in the MgM group and 1.6% in the control group (P = .09). The r-PHA was 0.23% in the MgM group and 0.92% in the control group (P < .01). Thus, the PHA was significantly shorter in the MgM group. Additionally, anatomical variations of the hepatic artery were confirmed in four cases. CONCLUSION: Preoperative radiological evaluation is not always adequate for identifying anatomical abnormalities in deceased donors. MgM is a rare but important anomaly because of the possibility of associated anatomical variations of the hepatic artery.

Thoracoscopic esophagectomy with extended lymph node dissection in the left lateral position: technical feasibility and oncologic outcomes.

The aim of this study was to estimate the technical and oncologic feasibility of video-assisted thoracoscopic radical esophagectomy (VATS) in the left lateral position. From January 2003 to December 2011, 132 patients with esophageal cancer underwent VATS. The mean duration of the thoracic procedure and the entire procedure was 294 ± 88 and 623 ± 123 minutes, respectively. Mean blood loss during the thoracic procedure and the entire procedure was 313 ± 577 and 657 ± 719 g, respectively. The mean number of dissected thoracic lymph nodes was 32.6 ± 12.9. There were four in-hospital deaths (3.0%); two patients (1.5%) died of acute respiratory distress syndrome and two patients (1.5%) died of tumor progression. Postoperative unilateral or bilateral recurrent laryngeal nerve (RLN) palsy, or pneumonia was found in 33 (25.0%), 21 (15.9%), and 27(20.5%) patients, respectively. The patients were divided into the first 66 patients who underwent VATS (Group 1) and the subsequent 66 patients (Group 2). The numbers of cases who underwent neoadjuvant or induction chemotherapy for T4 tumor and intrathoracic anastomosis were higher in Group 2 than in Group 1. The duration of the procedure, amount of blood loss, and the number of dissected thoracic lymph nodes were not different between the two groups. The total number of dissected lymph nodes was higher in Group 2 than in Group 1 (72.6 ± 27.8 vs. 62.6 ± 21.6, P = 0.023). The rate of bilateral RLN palsy was less in Group 2 than in Group 1 (7.6% vs. 24.2%, P = 0.042). The mean follow-up period was 38.7 months. Primary recurrence consisted of hematogenous, lymphatic, peritoneal dissemination, pleural dissemination, and locoregional in 15 (11.3%), 20 (15.1%), 3 (2.3%), 4 (3.0%), and 5 patients (3.8%), respectively. The rate of regional lymph node recurrence within the dissection field was only 4.5%. The prognosis of patients with lymph node metastasis was significantly poorer than that of patients without lymph node metastasis. However, the prognosis of the 11 cases that had metastasis only around RLNs was similar to that of node-negative cases. Thirteen patients with pathological remnant tumor (R1 or R2) did not survive longer than 5 years at present. The overall 5-year survival rate of stage I, II, and III disease after curative VATS was 82.2%, 77.0%, and 52.3%, respectively. Expansion of VATS criteria for patients after induction chemotherapy for T4 tumor or thoracoscopic anastomosis did not adversely affect the surgical results by experience. Although the VATS procedure is accompanied by a certain degree of morbidity including RLN palsy and pulmonary complications, VATS has an excellent locoregional control effect. In addition, the favorable survival after VATS shows that the procedure is oncologically feasible.

Development of a nuclear magnetic resonance system for in situ analysis of hydrogen storage materials under high pressures and temperatures.

A NMR system for in situ analysis of hydrogen storage materials under high pressure and temperature conditions was developed. The system consists of a gas pressure and flow rate controlling unit, a temperature controller, a high temperature NMR probe tunable for both (1)H and other nuclei, and a sample tube holder. Sample temperature can be controlled up to 623 K by heated N(2) gas flow. Sample tube atmosphere can be substituted by either H(2) or Ar and can be pressurized up to 1 MPa under constant flow rate up to 100 ml/min. During the NMR measurement, the pressure can be adjusted easily by just handle a back pressure valve. On the blank NMR measurement, (1)H background noise was confirmed to be very low. (1)H and (11)B NMR spectrum of LiBH(4) were successfully observed at high temperature for the demonstration of the system. The intensity of the (1)H NMR spectra of H(2) gas was also confirmed to be proportional to the applied pressure.

Role of transcription factors in small intestinal ischemia-reperfusion injury and tolerance induced by ischemic preconditioning.

BACKGROUND: Small intestinal ischemia-reperfusion (I/R) injury, a clinically important condition, induces severe organ damage. Ischemic preconditioning (IPC) produces tolerance to long-term I/R by inducing a short-term I/R. Herein, we have examined the reduction in the extent of injury by IPC. METHODS: Small intestinal I/R injury was induced in rats by clamping the superior mesenteric artery (SMA) for 30 minutes followed by reperfusion for various 30 minutes. The IPC + I/R group underwent a short-term I/R (IPC) prior to long-term I/R. Nuclear factor-κB (NF-κB) activity was analyzed by an electrophoretic mobility shift assay and cytokine mRNA levels, by reverse transcription-polymerase chain reaction. Apoptosis-related genes were analyzed by Western blotting and immunohistochemistry, and apoptotic cells, by TUNEL staining. RESULTS: The animals were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion. NF-κB activity increased in the I/R group and decreased in the IPC + I/R group. The IPC + I/R group showed decreased cytokine in mRNA levels. Expression of the proapoptotic gene caspase-3 was increased in the I/R and decreased in the IPC + I/R group. Expression of the antiapoptotic gene Bcl-xL was increased in the IPC + I/R group. The number of apoptotic cells was increased in the I/R and decreased in the IPC + I/R group. CONCLUSION: Small intestinal I/R injury was reduced by IPC produced by clamping the SMA; thus, IPC may have potential clinical applications in the future.

An increased dose of insulin detemir improves glycaemic control and reduces body weight of Japanese patients with diabetes.

AIMS: The aim of study was to evaluate the safety and efficacy of insulin detemir as a basal insulin switching from neutral protamine Hagedorn insulin (NPH) and insulin glargine in patients with diabetes on an intensive insulin therapy regimen. METHODS: This 6-month multicentre, prospective, treat-to-target [glycosylated haemoglobin (HbA(1c) ) less than 6.5%] trial included 92 people with diabetes (61 type 1, 29 type 2 and two unknown diabetes types). Detemir was administered first with fixed dose and injection times and then adapted to optimal dose after 3 months. RESULTS: Mean HbA(1c) (%) of all the subjects at months 4 to 6 of the study was improved compared with month 0 (7.34 ± 0.87, 7.28 ± 0.88, 7.25 ± 0.93 vs. 7.55 ± 1.18; p < 0.05 paired t-test). However, significant improvement was seen only among the patients who had previously used NPH as a basal insulin. Twice-daily injection of basal insulin increased among people in the type 1 previously injected insulin glargine. Total insulin dose increased in the type 1 glargine group. The mean body weight change in the highest quartile body mass index (BMI) group was from 70.7 to 69.3 kg over the 6 months. Quality of life (QoL) relating to the patients' glycaemic control tended to improve without a change in frequency of hypoglycaemia. CONCLUSIONS: The results suggest that insulin detemir has a greater effect on glycaemic control in subjects with poor glycaemic control using NPH; can reduce or maintain body weight in obese patients; and obtains perceptive stability for patients with unstable glycaemic control.

Learning of thoracoscopic radical esophagectomy: how can the learning curve be made short and flat?

Attainment of proficiency in video-assisted thoracoscopic radical esophagectomy (VATS) for thoracic esophageal cancer requires much experience. We have mastered this procedure safely under the direction of an experienced surgeon. After adoption of the procedure, the educated surgeon directed induction of this surgical procedure at another institution. We evaluated the efficacy of instruction during the induction period by comparing the results at the two institutions in which VATS had been newly induced. We defined the induction period as the time from the beginning of VATS to the time when the last instruction was carried out. From January 2003 to December 2007, 53 patients were candidates for VATS at Kanazawa University (institution 1). Of these, 46 patients underwent curative VATS by a single operator. We divided this period into three parts: the induction period of VATS, post-induction period, and proficient period when the educated surgeon of institution 1 directed the procedure at Maebashi Red Cross Hospital (institution 2). At institution 1, 12 VATS were scheduled, and nine procedures (75%) (group A) including eight instructions were completed during the induction period (from January 2003 to August 2004). Thereafter, VATS was performed without instruction. In the post-induction period, nine VATS were scheduled, and eight procedures (88.8%) (group B) were completed from September 2004 to August 2005. Subsequently, 32 VATS were scheduled, and 29 procedures (90.6%) (group C) were completed during the proficient period (from September 2005 to December 2007). The surgeon at Maebashi Red Cross Hospital (institution 2) started to perform VATS under the direction of the surgeon who had been educated at institution 1 from September 2005. VATS was completed in 13 (76.4%) (group D) of 17 cases by a single surgeon including seven instructions during the induction period at institution 2 from September 2005 to December 2007. No lethal complication occurred during the induction period at both institutions. We compared the results of VATS among four groups from the two institutions. There were no differences in the background and clinicopathological features among the four groups. The number of dissected lymph nodes and amount of thoracic blood loss were similar in the four groups (35 [22-52] vs 41 [26-53] vs 32 [17-69] vs 29 [17-42] nodes, P = 0.139, and 170 [90-380] vs 275 [130-550] vs 220 [10-660] vs 210 [75-543] g, P = 0.373, respectively). There was no difference in the duration of the thoracic procedure during the induction period at the two institutions. However, the duration of the procedure was significantly shorter in the proficient period of institution 1 (group C: 266 [195-555] minutes) than in the induction period of both institutions (group A: 350 [280-448] minutes [P = 0.005] and group D: 345 [270-420] mL [P = 0.002]). There were no surgery-related deaths in any of the groups. The incidence of postoperative complications did not differ among the four groups. Thoracoscopic radical esophagectomy can be mastered quickly and safely with a flat learning curve under the direction of an experienced surgeon. The educated surgeon can instruct surgeons at another institution on how to perform thoracoscopic esophagectomy. The operation time of thoracoscopic surgery is shortened by experience.

Prospective randomized controlled study on the effects of perioperative administration of a neutrophil elastase inhibitor to patients undergoing video-assisted thoracoscopic surgery for thoracic esophageal cancer.

Sivelestat sodium hydrate (Ono Pharmaceutical Co., Osaka, Japan) is a selective inhibitor of neutrophil elastase (NE) and is effective in reducing acute lung injury associated with systemic inflammatory response syndrome (SIRS). We conducted a prospective randomized controlled study to investigate the efficacy of perioperative administration of sivelestat sodium hydrate to prevent postoperative acute lung injury in patients undergoing thoracoscopic esophagectomy and radical lymphadenectomy. Twenty-two patients with thoracic esophageal cancer underwent video-assisted thoracoscopic esophagectomy with extended lymph node dissection in our institution between April 2007 and November 2008. Using a double-blinded method, these patients were randomly assigned to one of two groups preoperatively. The active treatment group received sivelestat sodium hydrate intravenously for 72 hours starting at the beginning of surgery (sivelestat-treated group; n= 11), while the other group received saline (control group; n= 11). All patients were given methylprednisolone immediately before surgery. Postoperative clinical course was compared between the two groups. Two patients (one in each group) were discontinued from the study during the postoperative period because of surgery-related complications. Of the remaining 20 patients, 2 patients who developed pneumonia within a week after surgery were excluded from some laboratory analyses, so data from 18 patients (9 patients in each group) were analyzed based on the arterial oxygen pressure/fraction of inspired oxygen ratio, white blood cell count, serum C-reactive protein level, plasma cytokine levels, plasma NE level, and markers of alveolar type II epithelial cells. In the current study, the incidence of postoperative morbidity did not differ between the two groups. The median duration of SIRS in the sivelestat-treated group was significantly shorter than that in the control group: 17 (range 9-36) hours versus 49 (15-60) hours, respectively (P= 0.009). Concerning the parameters used for the diagnosis of SIRS, the median heart rates on postoperative day (POD) 2 were significantly lower in the sivelestat-treated group than in the control group (P= 0.007). The median arterial oxygen pressure/fraction of inspired oxygen ratio of the sivelestat-treated group were significantly higher than those of the control group on POD 1 and POD 7 (POD 1: 372.0 [range 284.0-475.0] vs 322.5 [243.5-380.0], respectively, P= 0.040; POD 7: 377.2 [339.5-430.0] vs 357.6 [240.0-392.8], P= 0.031). Postoperative white blood cell counts, serum C-reactive protein levels, plasma interleukin-1beta, tumor necrosis factor-alpha levels, and plasma NE levels did not differ significantly between the two groups at any point during the postoperative course, nor did serum Krebs von den Lungen 6, surfactant protein-A, or surfactant protein-D levels, which were used as markers of alveolar type II epithelial cells to evaluate the severity of lung injury. Plasma interleukin-8 levels were significantly lower in the sivelestat-treated group than in the control group on POD 3 (P= 0.040). In conclusion, perioperative administration of sivelestat sodium hydrate (starting at the beginning of surgery) mitigated postoperative hypoxia, partially suppressed postoperative hypercytokinemia, shortened the duration of SIRS, and stabilized postoperative circulatory status after thoracoscopic esophagectomy.

Changes in the radical-scavenging activity of bitter gourd (Momordica charantia L.) during freezing and frozen storage with or without blanching.

The effects of blanching, freezing, and frozen storage on the retention of radical-scavenging activity (RSA), total phenolics, and ascorbic acid in bitter gourd were investigated. Blanching of sliced bitter gourd resulted in considerable losses of RSA and total phenolics, and most extensively, of ascorbic acid. In the subsequent frozen storage at -18 degrees C, RSA and total phenolic content of unblanched and blanched bitter gourd underwent little change for 90 d then gradually declined, but at -40 degrees C, they practically remained unchanged throughout the entire storage period. On the contrary, ascorbic acid content of both unblanched and blanched bitter gourd decreased abruptly at the early stage in frozen storage. The results show that blanching of bitter gourd improves the retention of RSA and total phenolics during subsequent frozen storage but markedly aggravated loss of ascorbic acid. Finally, it is to be noted that RSA, total phenolics, and ascorbic acid originally contained in the raw bitter gourd were overall best retained by quick freezing followed by frozen storage at -40 degrees C without preceding blanching.

Analysis of volatile flavor compounds of sardine (Sardinops melanostica) by solid phase microextraction.

Generally the main component of fishy flavor is considered to be trimethylamine. On the other hand, carbonyl compounds, produced from oxidation of polyunsaturated fatty acid by lipoxygenase or by autoxidation, might have some contribution to the fishy flavor. Since sardine skin contains high levels of polyunsaturated fatty acids and lipoxygenase, carbonyl compounds may be generated more easily than trimethylamine. In this study, volatile flavor compounds of sardine were analyzed by gas chromatograph-mass spectrometry and gas chromatograph-olfactometry combined with solid phase microextraction. Then, the flavor components that contribute to fishy flavor were identified. At normal pH (6.2), trimethylamine was not detected or sensed from the fresh sardines. When the pH was raised, the amount of trimethylamine became higher. Trimethylamine flavor was weak at pH 9 and strongly sensed at pH 11 or higher. On the other hand, 33 other compounds were positively or tentatively identified, including 8 hydrocarbons, 5 ketones, 1 furan, 1 sulfur compound, 12 aldehydes, and 6 alcohols in fresh sardines. Among them, 2,3-pentanedione, hexanal, and 1-penten-3-ol were the main components. Forty-seven flavors were detected by gas chromatograph-olfactometry. Among them, paint-like (1-penten-3-one), caramel-like (2,3-pentanedione), green-like (hexanal), shore-like ((Z)-4-heptenal), citrus note (octanal), mushroom-like (1-octen-3-one), potato-like (methional), insect-like ((E,Z)-2,6-nonadienal), and bloody note (not identified) were strongly sensed. From the aforementioned results, it can be concluded that these compounds rather than trimethylamine contributed to fresh sardine flavor.

Time and cost involved in the care of newly registered patients with diabetes mellitus and other lifestyle diseases at diabetes clinics in Japan (JDDM 4).

AIMS: To study the time and cost involved in the care of newly registered outpatients with Type 2 diabetes mellitus (DM), compared with patients with hypertension and/or hyperlipidaemia (HTL). METHODS: A total of 313 patients with DM and 58 patients with HTL without diabetes were registered on their first visits to 11 diabetes clinics across Japan. The time and cost involved in their care was recorded over the following 5 months. RESULTS: In the first 3 months, there was an extensive time commitment to both groups. The time spent by physicians was 1.5 times longer for DM than for HTL. The total care time spent by all the care providers for DM was twice that for HTL. The cost of DM care was twice that for HTL, with the cost of medicines excluded. However, half of the cost for DM was for laboratory tests. When these were excluded, and the remaining cost divided by the time spent, the amount for DM was half of that for HTL. Over the 5 months, mean glycated haemoglobin (HbA(1c)) in DM patients improved from 8.0% to 6.5%, and 72% of DM patients achieved the glycaemic target of HbA(1c) < or = 6.5%. CONCLUSIONS: DM care in a diabetes clinic requires a great deal more time and resources than HTL to achieve the best outcome. An educational system for self care, presently lacking in the primary care setting in Japan, would improve glycaemic control for DM patients in the community.

Sclerosing therapy of internal hemorrhoids with a novel sclerosing agent. Comparison with ligation and excision.

BACKGROUND AND AIMS: Patients with prolapsing internal hemorrhoids were treated with a novel sclerosing agent (OC-108), and the results were compared with surgery of ligation and excision. PATIENTS AND METHODS: This study included 20 years or older patients with prolapsing internal hemorrhoids who visited ten medical institutions in Japan from October 2000 to October 2002. Investigation on surgery was also performed. RESULTS: Comparing OC-108 and surgery in patients with third- and fourth-degree internal hemorrhoids according to the Goligher's classification, for which surgery has been generally indicated, at 28 days after treatment, the disappearance rate of prolapse was similar between OC-108 and surgery, 94% (75/80 patients) and 99% (84/85 patients), respectively. The 1-year recurrence rate was 16% (12/73 patients) in the OC-108 group, and this value was satisfactory because of its less invasive nature while it was more or less higher compared with 2% (2/81 patients) in the surgery group. The incidences of pain and bleeding were lower in the OC-108 group. CONCLUSIONS: OC-108 is a useful alternative treatment for hemorrhoids.

Multiple organ failure caused by end-stage liver disease successfully treated with living donor liver transplantation using perioperative percutaneous cardiopulmonary support: a case report.

A 54-year-old female diagnosed with primary biliary cirrhosis (PBC) 10 years earlier was referred for a living donor liver transplant (LDLT). During her workup, she developed pulmonary edema and respiratory failure due to aspiration pneumonia, which required artificial ventilation. The PaO2/FiO2 (P/F) ratio at that time was 60. Although continuous hemodiafiltration (CHDF) and plasma exchange (PE) were initiated, improvement in the P/F ratio was limited to 133. As transplantation was the only approach to save this patient, we performed LDLT using a right lobe graft aided by percutaneous cardiopulmonary support (PCPS). The graft weight was 650 g and the graft weight/recipient weight ratio was 1.6%. During LDLT, the patient's cardiopulmonary function was stable with PCPS, and the surgical procedure was completed without complications. Following the surgery, she continued to have high-end inspiratory pressure and progressed to the chronic phase of adult respiratory distress syndrome (ARDS). We treated her with low-dose steroid therapy and she improved gradually. The patient was weaned off mechanical ventilation and was discharged approximately 25 weeks after LDLT. In the condition of cardiac or respiratory failure, cadaveric liver transplantation using plasmapheresis is contraindicated because of the associated high mortality rate. Our case suggests that if infections are controlled, a patient with multiple organ failure (MOF) due to end-stage liver disease might be successfully treated with LDLT aided by plasmapheresis and PCPS.

A case of orbital solitary fibrous tumor.

BACKGROUND: Solitary fibrous tumor is a spindle cell neoplasm that most commonly arises in the pleura and very rarely involves the orbit. CASE: A 38-year-old woman presented with slowly progressive proptosis of 3 months duration and optic nerve head edema in her right eye. Magnetic resonance imaging revealed a well-circumscribed, round mass lesion, which showed isointensity to the gray matter in a T1-weighted image, and variegated intensity in a T2-weighted image and contact with the optic nerve in her right orbit. The tumor was successfully removed by anterior orbitotomy. OBSERVATIONS: The tumor showed a "patternless pattern" of tumor cell arrangement, alternating hypercellular and hypocellular areas, a hemangiopericytoma-like pattern, and thickened strands of collagen. Immunohistochemically, the tumor cells were positive for CD34 and vimentin, and all were negative for other markers of epithelial, neural, muscular, histiocytic, and vascular endothelial cell elements. The tumor was diagnosed as a solitary fibrous tumor, and the patient was doing well with no evidence of recurrence 15 months after surgery. CONCLUSIONS: This case was the 19th reported case of solitary fibrous tumor in the orbital region. CD34 is a highly sensitive marker for solitary fibrous tumor.