A 48% incidence of muscle cramps was found in 150 patients with liver cirrhosis. A 76.7% incidence of muscle cramps was found in patients with decompensated liver cirrhosis, which was statistically higher than a 36.4% incidence in patients with compensated liver cirrhosis.
In order to evaluate the effect of Hachimi-jio-gan on the treatment of muscle cramps in cirrhotic patients, 5g or 7.5g of Hachimi-jio-gan was administered orally to 31 cirrhotic patients (15 patients in the compensated stage and 16 patients in the decompensated stage), who had suffered from muscle cramps at a frequency of more than once a week. The frequency of muscle cramps was found to have decreased in all patients and to have completely disappeared in 19 patients (61.3% of 31 patients) following administration of Hachimi-jio-gan orally for 4 weeks.
The vibration perception threshold (VPT) was examined in 5 cirrhotic patients. The VPT improved in all patients in proportion to the decrease in the frequency of muscle cramps following administration of Hachimi-jio-gan orally.
The effect of Hachimi-jio-gan was compared to the effect of Gorei-san ane Shakuyaku-Kanzo-to on muscle cramps in 11 cirrhotic patients. The effective rates were 100%, 36.4% and 54.5% respectively. Judging from these results, Hachimi-jio-gan can be considered more effective in giving relief from muscle cramps. Hachimi-jio-gan was also effective in giving relief from muscle cramps in 6 cirrhotic patients in which Mecobalamin had no effect.
These results suggest that Hachimi-jio-gan is a useful drug for the treatment of muscle cramps in patients with liver cirrhosis.

The effect of changes in vascular transmural pressure upon differential digital plethysmogram (delta DPG) was studied in seven normal subjects. Changes in vascular transmural pressure were produced by the gravitational potential energy change (GPEC method) of an extremity from the heart level. Delta DPG which was characteristic of stability, discrimination and low speed record by modified devices was applied for the experiments including postural, static and dynamic exercises. Room temperature during experiments was kept constant. The Delta DPG-P wave amplitude in maximal elevation of upper and lower extremities (mean±S. D., n) increased to 162.3±33.5% (38) and 176.7±33.4% (12), respectively, and that in maximal lowering of upper and lower extremities decreased to 36.9±10.5% (35) and 37.5±12.6% (15), respectively. These data reveal that the GPEC method may be useful for the determination of arteriolar sensitivity in humans.

Objective: Celecoxib has been reported to enhance the action of warfarin by inhibiting CYP2C9, its major hepatic drug-metabolizing enzyme, but sufficient information about the mechanism has not been obtained, especially in Japan.
Methods: A study was conducted to investigate the prothrombin time international normalized ratio (PT-INR) and the warfarin sensitivity index (WSI) before and after concurrent administration of celecoxib, as well as the Drug Interaction Probability Scale (DIPS) scores to determine causality with drug interactions, in patients commencing concurrent therapy with celecoxib and warfarin at Kanagawa Prefectural Keiyukai Keiyu Hospital during the 4-year period from October 2011 to September 2015.
Results: Analysis of 18 patients showed that the PT-INR increased significantly from 1.53±0.43 before concurrent therapy to 2.18±1.01 after concurrent therapy (p=0.0101).  The WSI also increased significantly from 0.76±0.50 before concurrent therapy to 1.01±0.65 after concurrent therapy (p=0.0044).  According to the DIPS scores, the causal relation was not rated as “Highly Probable” in any of the patients, while it was considered to be “Probable” in 3 patients, “Possible” in 10 patients, and “Doubtful” in 5 patients.
Conclusion: The findings of this study suggested that when celecoxib treatment is initiated in patients who are already taking warfarin, attention must be paid to changes of coagulation profile, especially in elderly patients.

Edaravone is an agent developed as a free radical scavenger, and is useful in functional recovery of the brain after cerebral infarction. However, to the best of our knowledge no experimental studies have been made regarding the effect of edaravone on cerebral protection during aortic arch surgery. We investigated the pharmacological effect of edaravone experimentally, through selective cerebral perfusion under deep hypothermia. Twelve adult dogs (body weight 14.8±2.0 kg) were used, and selective cerebral perfusion was performed under hypothermic circulatory arrest of 20°C for 120 min at 5 mg/kg/min, which was half the usual flow volume of cerebral perfusion. Group E (n=6) received 3 mg/kg edaravone for 30 min at the start of both selective cerebral perfusion and rewarming of the body, while Group C (n=6) received no drugs. Somatosensory evoked potential (SEP) was measured, and so were blood pressure, body temperature, pH level, oxygen partial pressure, and blood flow in the cerebral tissue. Histopathological investigations were also performed. In Group E, complete SEP recovery was observed in all dogs, while in Group C, complete SEP recovery was observed in only 2 dogs (33%) (p=0.014). A statistically significant difference was also observed in cerebral tissue pressure (p=0.014), but not in pH level, oxygen partial pressure, or cerebral tissue blood flow. On histopathological investigation, Group C demonstrated reduced staining of Nissl granules in neurons of the cerebral cortex, and many of them presented the appearance of acute circulatory impairment while Group E demonstrated no reduction in staining of Nissl granules. In the present experimental study of selective cerebral perfusion under deep hypothermia below the safety threshold flow, edaravone was effective in cerebral protection.

Purpose: Evaluation of the efficacy and safety of sublingual drug administration in palliative care patients lacking the ability to swallow as well as other drug administration routes. Methods: Buprenorphine, 0.1∼0.2mg/dose (n=15) and fentanyl, 0.05∼0.2mg/dose (n=26) were administered sublingually for cancer pain, and midazolam, 0.1mg/kg (n=16) for insomnia respectively. Results: The three drugs were all rapidly absorbed by the oral cavity and showed efficacy in about 90% of patients. No adverse events were observed other than drowsiness, nausea and over production of sputum in patients suffering from dysphagia. Conclusion: Sublingual administration is a viable alternative for maintaining the quality of life of patients not accessible through conventional administration routes in the palliative setting. Palliat Care Res 2010; 5(1): 201-205

Coronary artery obstruction, pulmonary stenosis, aortic valve regurgitation, and enlargement of the neo-aortic root are major complications of arterial switch operation (ASO) for transposition of the great arteries (TGA). Supravalvular aortic stenosis following ASO is rarely reported, and technical factors should be considered as causes in such cases. We report a case of supravalvular aortic stenosis following ASO, in which we speculated that the cause of the stenosis was tissue overgrowth caused by the surgical suture. The patient was a 4-month-old girl with TGA (II) who had undergone ASO on the 12th day after birth. Neo-aortic anastomosis was performed with 7-0 polydioxanone absorbable suture (PDS^®, Ethicon, Somerville, NJ, USA). Transthoracic echocardiography performed 1 month after the surgery showed severe stenosis at the aortic anastomosis which worsened progressively. Therefore, the patient was reoperated 4 months after the previous surgery. The concentrically stenosed aortic wall at the anastomotic site was resected and aortic reanastomosis was performed using an interrupted suture pattern with 7-0 polypropylene (Prolene^®, Ethicon). The histological findings showed proliferation of collagenous fibers around the PDS^® suture. Because of the worsening stenosis over time and the histological findings, we speculated that the tissue overgrowth in reaction to the PDS^® suture was the main cause of the stenosis. Absorbable sutures are useful because they do not leave a foreign substance in the body ; however, the possibility of tissue overgrowth leading to anastomotic stenosis cannot be denied. When using absorbable suture, careful observation is mandatory until the material is completely absorbed.

A regular check-up in a 69-year-old man showed normal blood chemistry values, except for elevated value of liver enzymes and inflammatory reactions. A computed tomography scan (CT) of the abdomen revealed a normal appearance of the liver, pancreas and spleen, but incidentally showed a tumor in the right atrium. The tumor (a blood cyst which contained white thrombus) was successfully excised. Blood cysts of the heart are extremely rare in adults. These tumors are incidently found at autopsy on cardiac valves in approximately 50% of infants under 2 months of age. The blood cyst in this case arose from the right atrial wall, which is also quite rare.

A 48-year-old man complained of hemoptysis. Chest CT scan showed a large cardiac tumor invading the atrial septum and both atria, as well as multiple small nodules in bilateral lung fields. They were diagnosed as a malignant cardiac tumor and its lung metastases. As the tumor in the left atrium was extremely massive, operation was performed to prevent sudden death due to occlusion and to make a pathological diagnosis. The cardiac tumor invaded the atrial septum from the right atrium and occupied the left atrium. After the cardiac tumor was completely removed, the bilateral atria, the atrial septum, SVC, IVC and the right lower pulmonary vein were reconstructed with prosthetic pericardial patches. The tumor was angiosarcoma. During the postoperative period, Interleukin-2 was used as the treatment for angiosarcoma. Unfortunately the patient died of lung failure on the 107th postoperative day. Though IL-2 could not stop the development of lung metastasis in this case, the effectiveness of radiotherapy or IL-2 for angiosarcoma has recently been reported. In such cases where complete resection of the primary cardiac lesion is possible, postoperative radiotherapy or IL-2 administration seems to be effective for cardiac sarcoma.

Detection of the coronary artery is usually an easy procedure in the coronary artery surgery. However in cases with an intra-muscular and/or intra-fat coronary artery, it requires special skill and experience. Dissection of epicardial adipose tissue and/or muscle along the epicardial groove is a common procedure to reach such coronary artery in conventional CABG (C-CABG). Recently, off-pump CABG (OPCAB) has become a standard operation, and detection of such a coronary artery is difficult under the beating heart. Then conversion to the C-CABG becomes necessary to avoid ventricular rupture. We report a new procedure to easily detect such a coronary artery in OPCAB, using an ultrasonic Fowmeter used in neurosurgery. Because the tip of the probe is small (2mm in diameter) and flexible, its handling is quite similar to that of the micro-blade knife. Furthermore, audiable Doppler flow sound allows detection and dissection of the coronary artery without looking away from the operative field to check the coronary flow. In our case, use of the instrument enabled us to detect the anterior descending branch of the left coronary artery which was very deep in adipose tissue. Therefore, application of this ultrasound instrument is beneficial in OPCAB with an intra-muscular and/or intra-fat coronary artery.

Background: We evaluated the effectiveness of gemcitabine and paclitaxel therapy in patients with metastatic urothelial carcinoma for whom two lines of sequential chemotherapy had been unsuccessful.

Methods: A total number of 105 patients who had previously received first-line chemotherapy consisting of gemcitabine and cisplatin or carboplatin, were treated with second-line gemcitabine and docetaxel therapy between June 2006 and May 2015. Of these patients, 15 with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 were administered gemcitabine and paclitaxel as third-line treatment from 2013 after failure of the second-line therapy. For each 21-day cycle, gemcitabine (1000 mg/m²) was administered on days 1, 8, and 15, and paclitaxel (200 mg/m²) on day 1. Patients were assessed for each cycle and any adverse events were noted. Furthermore, a Short Form Health Survey questionnaire was used to assess each patient’s quality of life.

Results: Third-line gemcitabine and paclitaxel treatment cycles were undertaken for a median of four times (range 2–9). The disease control rate was 80.0%. After second-line gemcitabine and docetaxel therapy was completed, median progression-free survival and median overall survival were determined as 9.8 and 13.0 months, respectively. The only prognostic factor for overall survival, as determined by univariate and multivariate analyses, was third-line gemcitabine and paclitaxel therapy. Neutropenia (66.7%) and thrombocytopenia (53.3%) were noted as the grade 3 treatment-related toxicities. After two cycles of third-line gemcitabine and paclitaxel therapy, the pre- and post-treatment quality of life scores did not differ significantly.

Conclusions: Results demonstrate that third-line combination therapy using gemcitabine and paclitaxel is a feasible option for metastatic urothelial carcinoma patients.