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An ethoxycarbonyl 1-ethyl hemiacetal ester of levofloxacin (LVFX-EHE) avoids insoluble chelate formation with metal-containing drugs in the intestinal tract and is rapidly hydrolyzed to the parent drug. Furthermore, the minimum inhibitory concentration confirms that LVFX-EHE is less likely to cause pseudomembranous colitis because of less susceptibility to normal intestinal bacteria flora. Pemetrexed dimedoxomil, the prodrug of pemetrexed, was synthesized via reaction with medoxomil bromide after modification of L-glutamate with the tert-butyloxycarbonyl protecting group (BOC), followed by hydrolysis of the BOC moiety with trifluoroacetic acid (TFA) in CH 2 Cl 2 at a temperature of 0°C for 2 h. A serum pemetrexed concentration of >2 μg/mL was observed after oral administration of pemetrexed dimedoxomil at a dose of 60 mg/kg to rats.

A 17-year-old boy developed prominent mediastinal and subcutaneous emphysema while receiving treatment with 5-aminosalicylic acid (5-ASA) and oral corticosteroids for severe ulcerative colitis. We ruled out infection and initiated oral administration of tacrolimus, after which both the underlying disease and mediastinal and subcutaneous emphysema improved. However, he continued to experience repeated bouts of ulcerative colitis, so we ultimately opted for surgical intervention. Although mediastinal and subcutaneous emphysema is rare, it is one of the known extra-intestinal complications and can be particularly concerning. In this patient, mediastinal and subcutaneous emphysema might have been caused by the vulnerability of pulmonary alveolar walls to steroid medication and the increase of pulmonary alveolar pressure with abdominal pain and breath holding. Here, we report a case of inflammatory bowel disease with mediastinal and subcutaneous emphysema, along with a review of the literature.

Background: Aeroperitoneum increases intra-occular pressure (IOP). We measured IOP during robotic-assisted laparoscopic radical prostectomy (RALP) that requires steeper Trenderenburg position., Methods: Fourteen patients with no ocular diseases were candidates. We measured their IOP during robotic operation from beginning to end., Results: Our date shows that IOP continues to increase over the time of steep Trenderenburg position., Conclusions: Long time RALP might be risky for IOP.

Pain and stress alleviation after acupuncture treatment was assessed in this study. Patients responded to a questionnaire designed to determine the amount of stress they were experiencing, and data were obtained for patient salivary amylase, cortisol, secretary IgA (s-IgA), and leptin receptor (OBRb). As a part of this study on acute pain, 6 factors were extracted from the questionnaire. The second factor (pain removal) was well correlated with salivary amylase activity in patients with cervico-omo-brachial syndrome. An evaluation of cumulative acupuncture treatments showed that salivary cortisol increased and s-IgA decreased. In addition, a decreased s-IgA level significantly correlated with chronic pain removal. The questionnaire correlated well with measurements of salivary markers suggesting that they can be taken as indices of therapeutic efficacy in acupuncture treatment.

Since 2005, the Japanese pharmacy education program has changed to a six year-system from a four year-system with the aim to help students obtain a higher level of clinical knowledge and skill regarding humanity and morality. Under the new pharmacy education system, the correct assessment of vital signs is observed in pharmacy practice so that pharmacists can sell "over the counter drugs (OTC)" safely. From this point of view, we started a pharmacy practice that recognizes a series of vital signs, i.e., blood pulse, blood pressure, respiratory sound, and electrocardiogram, using a physical figure subjecting to 4th-year students (n=142) . After the practice, a questionnaire was conducted in order to assess the satisfaction of the practice. The results suggested that students could successfully learn physical assessment by using physical figures (ratios more than grade 4: 60%). Students could also evaluate the necessity of physical assessment (ratios more than grade 4: 70%), suggesting the practice of using physical figures was accepted by most students.

Background: Although Airtraq (ATQ) is well accepted as a useful device for tracheal intubation especially in cases of difficult airway management, we sometimes encounter difficulty in insertion of a tracheal tube along the blade of ATQ across the vocal cord in spite of ATQ assistance. Gum Elastic Bougie (GEB) is well known as a practical device for intubation assistance with Macintosh laryngoscope. We studied the efficacy of GEB for intubation with ATQ., Methods: One-hundred-forty one patients scheduled for general anesthesia, ASA physical status 1 or 2, were allocated into two groups randomly; patients intubated with ATQ without GEB (n = 70), and those with ATQ with GEB (n = 71). Twenty anesthegiologists were assinged to them evenly according to their experience. We measured the time they needed for intubation., Results: The combinational advantage of ATQ and GEB was not significantly proved among board certified anesthesiologist. However, among non-board-certified anesthesiologist group, the time needed for successful intubation was significantly shorter with combined use of ATQ and GEB., Conclusions: For the people with less experience of intubation, GEB is useful assistance for intubation with ATQ. It was concluded that the combined use of ATQ and GEB is a simple and effective process for ordinary doctors or paramedics.

Acute massive pulmonary thromboembolism (APE) is still associated with a high mortality rate. Furthermore, significantly higher mortality rates are observed in patients who underwent cardiopulmonary resuscitation (CPR) because of severe brain damage or multiple organ failure. We present successfully treated 4 patients who were transferred from outside hospitals under continuous CPR. Three of 4 patients required percutaneous cardiopulmonary support (PCPS). Preoperatively, all 4 patients had no brain damage despite of CPR for a maximum of 40 minutes. Open pulmonary thrombectomy was successfully performed under on pump beating cardiopulmonary support. All patients dramatically improved and were discharged without any complication. When hemodynamic instability or cardiac arrest occurs in patients with APE, rapid CPR, rapid diagnosis with echocardiography, and quick PCPS establishment are keys in our management strategy.

In Japan, XELOX (capecitabine plus oxaliplatin) was approved for the treatment of advanced/recurrent colorectal cancer in September 2009. However, patients treated with XELOX sometimes experience intense, sporadic venous pain during administration of oxaliplatin through peripheral vein. To investigate the etiology and management of this event, we measured the titratable acidity, osmotic pressure, and pH of 5% dextrose in water (D5W) containing oxaliplatin with or without dexamethasone. The dexamethasone-containing solution was then tested for its efficacy in venous pain relief. D5W containing oxaliplatin had a pH of approximately 4. 8, whereas the titratable acidity and osmotic pressure were 0. 1 mEq/L and 300-320 mOsm/L, respectively, suggesting that the venous pain was partly attributable to the pH.When 1. 65-6. 6 mg of dexamethasone was added to this solution, the pH of the resulting solution was increased to 6. 5-7. 6. Moreover, pain was relieved in patients administered oxaliplatin with dexamethasone in D5W. When adjusted for pH by the addition of 1. 65-3. 3 mg of dexamethasone, oxaliplatin in D5W is associated with less venous pain without decreasing oxaliplatin content although it is not generally recommended to dissolve oxaliplatin in a basic solution since it is unstable under alkaline conditions.

The six-year pharmacist education course has begun, and now first-year students receive clinical training. Interdisciplinary problem-solving capabilities covering chemistry, biology, molecular biology, pharmacology, pathology, and pharmacokinetics are necessary for new pharmacists. However, the conventional pharmaceutical science education was so separate from other fields that education for interdisciplinary cooperative capability was insufficient. This was especially true of elemental science courses, because they are not directly connected with clinical knowledge, and there is a problem of low student interest in those courses. As a result, students acquired only recall-level knowledge in clinical courses and their problem-solving capabilities in clinical treatment and drug development deteriorated. Therefore we offered a trial lecture aimed to help students recognize the important relationship between elemental science courses and clinical courses and increase their motivation to enroll in these courses. Specifically, the trial lecture covered cancer therapy, in reference to mechanisms of carcinogenesis, epidemiology, physiology of cancer, anticancer drugs with explanations of the mechanism of action of carcinogens, anticancer drugs, and molecular-targeted drugs from the viewpoints of organic chemistry and biochemistry by a specialized teacher. This paper reports on this experimental lecture with evaluations from students.

One of the fundamental characteristics of animal is locomotion. Although not visually apparent, goal-directed locomotor movements are always accompanied by automatic adjustment of muscle tone and postural reactions. Because the basic and essential mechanisms that control postural muscle tone and locomotion are located in the brainstem and spinal cord, a variety of locomotor behaviors are achieved by the projections from the forebrain structures (cerebral cortex, basal ganglia, and limbic-hypothalamic systems) and cerebellum to the brainstem-spinal cord. In this short review, we particularly focus on the role of the brainstem and spinal cord in the control of postural muscle tone and generation of locomotor rhythm. Abnormalities in the convergence inputs from the forebrain structures to the brainstem-spinal cord are further discussed in relation to the pathogenesis of disturbances in locomotor control.

Cancer pain often makes patient's performance status worsen and is one of the difficulties in anti-cancer therapy. We report a case of unresectable advanced pancreatic cancer with cancer pain, which was treated by matrix-type transdermal fentanyl following slow-releasing oxycodone, which caused severe constipation. Rotation to matrix-type transdermal fentanyl (Durotep MT 2.1 mg) releaved severe constipation as well as cancer pain. The patient could take gemcitabine-based chemotherapy. Low-dose matrix-type transdermal fentanyl (Durotep MT 2.1 mg) is useful for opioid rotation from low-dose morphine or oxycodone with uncontrolled side effects, and it contributes to continuation of anti-cancer therapy.

We present a 68 years old woman who was referred to our department due to impaired liver function. Hepatitis A IgM antibody and anti-nuclear antibody were positive, IgG, and gamma-globulin were elevated. Percutaneous liver biopsy was performed and autoimmune hepatitis was suspected pathologically. Oral administration of ursodeoxycholic acid was started and liver function was normalized three months later. The improvement of a hepatitis image was examined by percutaneous liver biopsy one year later. Although hepatitis A IgM antibody was positive throughout the course, hepatitis A virusemia was not considered the cause of persistent positive hepatitis A. IgM antibody could not be clarified. There was a possibility of a non-specific reaction and abnormalities in antibody production control were considered possible. We present this case and discuss the previous literature.

A 45-year-old woman with a local recurrence on her left chest wall discharged massive exudates. At every gauze exchange, blood was still oozing out. After using Mohs paste twice, the surface had been fixed chemically and dried up, so she did not have to exchange gauze, and there was no more bleeding. A 55-year-old woman was suffering massive exudates and offensive smell from her right primary breast cancer that formed a massive bulge with a deep ulcer in the center. Because her serum hemoglobin declined to 4.4 g/mL due to continuous bleeding, she needed to undergo blood transfusion. After using Mohs paste twice, the bleeding stopped almost completely. Now she uses Mohs paste by herself at home at her convenience. A 69 year-old woman suffered from an offensive odor and continuous bleeding from a local recurrence in the skin of her abdomen. A single use of Mohs paste relieved her from bleeding and the smell. Three patients had experienced no adverse events except mild pain and their QOL improved considerably. Mohs paste is in the hope of improving the QOL for the breast cancer patients with local advanced, unresectable skin lesions.

At Osaka National Hospital, we opened a palliative care team (PCT) since July 2004. The PCT advises the symptom management of cancer patients and supports patients' decision making. By March 2006, 355 consecutive cancer patients referred to the PCT, including 221 patients with psychiatric symptoms. The duration of the treatments for psychiatric symptoms were extended longer than for physical symptoms (physical symptoms: 47.7 days, depression: 60.4, delirium: 56.0, adjustment disorders: 57.4; p < 0.05). The reasons for this prolongation are that psychiatric symptoms (especially delirium) are often overlooked, and that home doctors and visiting nurses often hesitate to take on the home medical care because of unfamiliarity with them. The management of psychiatric symptoms at home is important for appropriate end-of-life care. The PCT and regional doctors have to work closely in cooperating with the successive palliation when the patient is transformed to home medical care.

Case 1: An 82 year-old female had a drop-foot, livedo reticularis and paresthesia. MPO-ANCA was positive. Because of developing renal dysfunction, she underwent steroid pulse therapy and dialysis, but died from the complication of congestive heart failure. Autopsy revealed necrotizing arteritis in the interlobular arteries and the arcuate arteries of the kidneys. Crescent formation was not found in the glomeruli. Case 2: A 49-year-old male had a drop foot and numbness. MPO-ANCA was positive. Because of developing renal failure, he underwent dialysis and steroid pulse therapy. MPO-ANCA became negative. Nevertheless, he developed perforation of multiple ulcers in the small intestine and died. Pathohistology revealed arteritis in medium-size arteries at the branch level of the mesenteric arteries. Since the presented two cases showed rapidly and irreversibly aggravated renal function with positive MPO-ANCA, MPA was suspected. However, pathological findings from the autopsy and operation and not the kidney biopsy supported the diagnosis of polyarteritis nodosa (PN). Vasculitis in the arterioles was absent. MPO-ANCA is not specific, and it can be detected in not only MPA, but also PN. The clinical course and pathological findings must be considered to differentiate PN from MPA.

A total of 42 patients with combined valvular and coronary artery surgery were examined to analyze risk factors for cardiac related events and late deaths. There were aortic valve disease in 26 patients and mitral valve disease in 16. Preoperatively, 14 patients (33%) had cardiac dysfunction (ejection fraction < or = 40%) and 10 patients (24%) were in New York Heart Association (NYHA) functional class IV. There was no operative death with 96% of early graft patency. There was 8 late deaths during 5.6 years of mean follow up. Actuarial survival rate was 86% and 64% after 5 and 10 years, respectively. Cardiac dysfunction was a significant independent predictor for late death. Cardiac related events occurred in 9 patients. Freedom from cardiac related events was 78% and 59% after 5 and 10 years, respectively. Cardiac dysfunction and mitral valve surgery were significant independent predictors for cardiac related events. Late result of combined mitral and coronary artery surgery was unfavorable in patients with cardiac dysfunction.

From March 1998 to May 2002, we experienced 46 patients with type A acute dissection (AAD). Fifteen patients managed initially with conservative treatment because of intramular hematoma (IH, n = 10), broad cerebral infarction (n = 3), others (n = 2). One who diagnosed IH at admission progressed to AAD and underwent surgery. However his diagnosis of IH at admission was proved to be misdiagnosis retrospectively. In 8 of the remaining 9 patients, hematoma disappeared during the follow-up of 6 months to 1 year. In patients with broad cerebral infarction, 2 died early after admission and 1 discharged with hemiplegia. Thirty-two patients underwent surgery and 1 with preoperative broad cerebral infarction died 36 days after surgery. In the remaining 31 patients, 30 patients discharged ambulatory.

[Case 1]: An 81-year old man was referred to our hospital with dyspnea and bloody sputum. Computed tomography with contrast medium for the evaluation of metastasis of urinary bladder carcinoma had been performed 4 months previously. On admission, his serum creatinine and potassium were 15.3 mg/dl and 6.9 mEq/l, respectively. His chest X ray revealed cardiomegaly, butterfly shadow and interstitial change, indicating congestive heart failure and interstitial pneumonia. His electrocardiogram showed that he was on the brink of cardiac arrest due to hyperkalemia. Mechanical ventilation and hemodialysis were initiated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) was highly positive(321 EU), leading to the diagnosis of MPO-ANCA-associated rapidly progressive glomerulonephritis (RPGN) with interstitial pneumonia. Treatment with pulse methylprednisolone was not effective and he died. Autopsy findings showed crescentic glomerulonephritis, alveolar hemorrhage and interstitial pneumonia with honeycomb formation. [Case 2]: A 73-year old man was referred to our hospital with rapid deterioration of his renal function. He had received a cardiac catheter examination 3 weeks previously. On admission, his serum creatinine was 4.5 mg/dl. His chest X ray showed cardiomegaly and interstitial change. Renal biopsy findings showed crescentic formation in the glomeruli. Moreover, MPO-ANCA was 494 EU, leading to the diagnosis of MPO-ANCA-associated RPGN with interstitial pneumonia. Treatment with pulse methylprednisolone and cyclophosphamide was not effective and he died. Autopsy findings revealed crescentic glomerulonephritis and interstitial pneumonia with honeycomb formation. Here we described two cases of ANCA-associated RPGN complicated by microscopic polyantitis and interstitial pneumonia after the use of contrast medium. The relation between ANCA-associated RPGN and the contrast medium was unclear. However, in the case of rapid deterioration of renal function, MPO-ANCA should be measured even after the use of contrast medium. The complication of lung diseases, especially interstitial pneumonia, should be investigated simultaneously.

Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.

An 86-year-old man with severe chest pain and shock was transferred to our hospital. Computed tomography revealed type A aortic dissection with cardiac tamponade. He needed intubation and closed chest massage preoperatively. At operation, intrapericardial space was filled with clotted blood and rupture of the ascending aorta was confirmed. He underwent a successful emergency graft replacement of the ascending aorta. Postoperative course was uneventful except for mild hemianopsia due to cerebral infarction. He had recovered to be able to walk and is doing well.

A 56-year-old male patient underwent a right upper lobectomy and lymph node dissection for non-small cell lung cancer in March 1994. Multiple lung metastases in the right lung were found 45 months after the operation, and chemotherapy with docetaxel was administered. A liver metastasis was detected 11 months later, and it was refractory to docetaxel. Therefore, the patient was treated with cisplatin, mitomycin C and vinorelbine, which resulted in no change to the liver metastasis. He was next treated with gemcitabine, which resulted in a partial response of the liver metastasis. The adverse effects of gemcitabine were Grade 3 thrombocytopenia and Grade 2 neutropenia. The response duration for gemcitabine therapy was three months.

A 73-year-old woman underwent docetaxel therapy for lung metastasis from breast cancer after having received CAF therapy. Because of the progressive disease due to secondary resistance to docetaxel, the patient was given three courses of paclitaxel therapy (60 mg/m2, day 1, 8, 15 and 22, repeated every 6 weeks). The paclitaxel therapy brought about no adverse effects and a 51%-reduction in the size of the metastatic lung tumor (PR). Although the duration of the response to the paclitaxel therapy was limited to about one month due to progression of a brain metastasis, paclitaxel therapy may be effective against docetaxel-resistant breast cancer.

Surgical outcome for thoracic aortic aneurysms involving the distal arch via a left thoracotomy using retrograde cerebral perfusion combined with profound hypothermic circulatory arrest was reviewed. Twelve patients with a atherosclerotic aortic aneurysm between 1994 and 1997 were involved. A proximal aortic anastomosis was made by means of an open aortic technique. For the first four patients, oxygenated arterial blood from cardiopulmonary bypass was perfused retrogradely through a venous cannula positioned into the right atrium. In the last eight cases, venous blood provided by a low-flow perfusion of the lower half body via the femoral artery, which was still oxygen-saturated, was circulated passively in the brain in a retrograde fashion with the descending aorta clamped. Prosthetic replacement was done between the distal arch and the proximal descending aorta in 6 patients and from the distal arch to the entire descending thoracic aorta in 6 patients. The median duration of hypothermic circulatory arrest and continuous retrograde cerebral perfusion was 36 minutes and 33 minutes respectively. The overall outcome was satisfactory without early mortality--all patients survived, although an octogenarian died of respiratory failure 1 year postoperatively. Another octogenarian with a ruptured aneurysm developed delay of meaningful consciousness, and other two patients with a severely atherosclerotic aneurysm suffered permanent neurological dysfunction (stroke) presumably due to an embolic episode. The safe and simple combination of profound hypothermic circulatory arrest, retrograde cerebral perfusion, and open aortic anastomosis protects the brain adequately and produces satisfactory results in surgery for aortic aneurysms involving the distal arch through a left thoracotomy.

Twenty-nine patients who underwent right ventricular outflow tract reconstruction using a valved conduit 37 times and survived surgery, were reviewed in this study. Hancock, Ionescu-Shiley, Carpentier-Edwards and Polystan was used for RVOTR. Freedom from reoperation rates of Hancock, Ionescu-Shiley and Carpentier-Edwardsat at five and ten years after surgery were 100%, 85.7%, 89.2% and 75%, 28.6%, 89.2%, respectively. The freedom from reoperation rates of Hancock and Carpentier-Edwards were significantly higher than that of Ionescu-Shiley. In conclusion, the freedom from reoperation rate at ten years was high for both Hancock and Carpentier-Edwards.

Forty-eight patients who underwent right ventricular outflow tract reconstruction with Monocusp Ventricular Outflow Patch (MVOP) fifty-five times and survived surgery, were reviewed in this study. Mean age at surgery was 6.4 years-old and mean follow-up interval was 75.2 months. There was no late death, however reoperation was performed 7 times. Freedom from reoperation rate was 97.2% and 80.7% after 5 and 10 years after surgery, respectively. The main cause for reoperation were right ventricular outflow obstruction RVOTO (5 cases). All of the RVOTO occurred at the distal end of the anastomosis. However, there was no RVOTO in patients who underwent RVOTR with MVOP during the past ten years. So, we considered the cause of RVOTO a technical problem. Pulmonary regurgitation was one to two degree early after surgery, and had worsened by almost two or three degrees more than 5 years after surgery. Moreover, five of six patients who underwent cardiac catheterization more than 10 years after surgery had three degrees of pulmonary regurgitation as well as a large CTR. In conclusion, according to long-term results, especially more than 10 years post operatively, pulmonary regurgitation was the most important problem.

From March 1980 to August 1997, 42 patients with complete transposition of the great arteries (TGA) type I and II underwent arterial switch procedure (n = 20) or Senning (n = 22) procedure in our institution. In arterial switch procedure group, there were two operative death. No late death occurred, and one patient underwent reoperation and one underwent balloon pulmonary angioplasty for right sided obstruction. The freedom from the intervention rate for right sided obstruction was 83.0% at 5 years, subsequently. In Senning procedure group, operative death occurred in two patients with TGA type II, and one patient with TGA type II and two patients with type I died because of cardiac events in the late stage. In this group, two patients died from accident. The survival rate excluding accidental deaths was 77.7% and 77.7% at 5 and 10 years, respectively. However, those patients who died in the late stage had severe pre-operative and post-operative complication. In conclusion, mid-term results of arterial switch procedure is satisfactory, however, reintervention rate was not so low. Long term results of Senning procedure without preoperative or postoperative complication was satisfactory.

We examined the chemosensitivity of non-small cell lung cancer (NSCLC) tissues to CDDP, 5-FU, ADM, MMC, ETP and SN38 using histoculture drug response assay (HDRA). One-hundred and thirty surgical specimens from NSCLC patients who were not given preoperative chemotherapy were used. The inhibition indexes of CDDP, 5-FU, MMC, ADM, ETP and SN38 were 39.1 +/- 18.2%, 48.0 +/- 19.7%, 63.3 +/- 17.7%, 47.6 +/- 22.0%, 36.9 +/- 21.1%, and 37.9 +/- 25.2%, respectively. Inhibition indexes were above the cutoff level, i.e., 'judged sensitive,' in 40 cases (31.3%) for CDDP, 34 cases (27.4%) for 5-FU, 54 cases (44.3%) for MMC, 36 cases (33.0%) for ADM, 29 cases (29.8%) for ETP, and 34 cases (37.4%) for SN38, respectively. In almost one-third of patients, the inhibition indexes of all drugs were under cutoff levels. Correlations between in vitro chemosensitivity data and patient responses to chemotherapy were obtained from 16 evaluable patients, and a 44.4% true positive rate and a 100% true negative rate were observed. Our results with HDRA for NSCLC showed a high incidence of intrinsic multidrug resistance. HDRA may help doctors to avoid non-effective chemotherapy for NSCLC patients.

Beta-adrenoceptor blocking agents (beta-blockers) have been widely used for the treatment of angina pectoris. The average/standard therapeutic doses vary widely among beta-blockers with the maximum of about a 120-fold difference. In order to clarify the mechanism of this difference, we analyzed retrospectively the pharmacological effects of beta-blockers in consideration of the beta 1-receptor binding affinity and the vasodilative activity on the basis of pharmacokinetics and the receptor occupancy theory. The analysis was performed on eight beta-blockers without a vasodilative effect and on four beta-blockers with a vasodilative effect. The beta 1-receptor occupancies at the steady-state condition after oral administration of standard doses were calculated by the use of the data on the concentration of unbound agents in plasma and on the dissociation constant of receptors. The estimated receptor occupancies were 87 +/- 6% or 88 +/- 10% for the beta-blockers with or without a vasodilative effect, respectively, and a significant difference was not observed between these groups. These results suggest that the beta 1-receptor occupancies may be a principal indicator for the therapeutic effects for angina pectoris regardless of their vasodilative effects.

Between May 1979 and September 1998, 202 children underwent surgical treatment for valvular heart disease. Of these 23, who ranged in age from 25 days to 15 years, underwent valve replacement, including 1 reoperation. The valve replacement consisted of the aortic valve in 5 patients, the mitral valve in 3, the tricuspid valves in 9, including 5 systemic atrioventricular valves for atrioventricular discordance, the pulmonary valve in 6, 5 bioprostheses and 18 mechanical prostheses. There were 4 operative deaths, 1 hospital death and 3 late deaths. At the 10-years follow-up, the actual survival rate was 67.8%, the event free rate was 76.1% and the freedom from reoperation rate was 86.2%. Valve re-replacement was performed in only 1 patient due to a thrombosed tricuspid valve. These results suggest that there is a small risk of major complications and reoperation in children who undergo valve replacement, whether a bioprosthetic valve or a mechanical valve. The long-term results of younger patients should be followed more closely according to their growth.

From January 1986 to May 1998, 45 lung cancer patients with chest wall invasion (P3) underwent resection (40 male, 5 female), (median age 63.2 yrs (30-79)). Histological types were squamous cell carcinoma in 20, adenocarcinoma in 14, large cell carcinoma in 7, adenosquamous cell carcinoma in 2, and unknown in 2. Operative methods of lung resection were total pneumonectomy in 2, bilobectomy in 3, lobectomy in 38, and partial lung resection in 2. Resection was regarded as complete in 35 and incomplete in 10 patients. Thirty one patients had negative lymph nodes (N0), 9 had peribronchial or hilar lymph node metastases (N1), and 5 had mediastinal lymph node metastases (N2). The extent of tumor invasion to chest wall was P3a (invasion within parietal pleura) in 11, P3b-c (invasion to intercostal muscle) in 16, P3d (invasion to rib) in 18, patients. 5-year survival rate was totally 19.7%. Cisplatin based chemotherapy and concurrent thoracic radiation following surgery (CCRT) was performed in latest nine P3d cases. Partial response was observed in 5 of 9 cases (response rate 56%) and viable tumor cell in the primary site was not seen histologically in 5 of 9 cases. Three year survival rate was 46.9% for CCRT(+) 11.1% for CCRT(-). Acturial 5-year survival rate in P3a-d was 19.76%. P3d cases had poor survival, but CCRT improved prognosis of P3d cases.

We treated a 1-year 9-month-old boy with severe hemophilia A who developed high level of F VIII inhibitor. A placement of an implantable intravenous access device was scheduled under general anesthesia. After a slow induction using oxygen, nitrous oxide and sevoflurane, a peripheral venous line was placed and plasma-derived F VII a was infused. A catheter was inserted via the jugular vein to the SVC and it was connected to the device placed subcutaneously in his right chest wall. The peroperative blood loss was slight, and anesthesia and surgery went uneventfully.

An 11-year-old boy with tetralogy of Fallot had undergone palliative right ventricular outflow tract reconstruction twice previously. After the second palliative surgery recurrent mediastinitis persisted. At the age of 5 years and 11 months, he underwent closure of VSD and reconstruction of the right ventricular outflow tract with an equine pericardial patch after removal of the infected prosthetic material. The postoperative course was uneventful, however, severe pulmonary stenosis developed 6 years later. The stenosis was caused by the severely deformed and calcified equine pericardial patch used for intracardiac repair. The reason for severe calcification seemed to be the accentuated calcium metabolism in children, hemodynamic stress and persistent infection.

We treated 10 cases of thoracic malignancy accompanied with cardiovascular disease. Among thoracic malignancy, 7 cases were lung cancer and 3 were esophageal cancer. Accompanied cardiovascular diseases were ischemic heart disease (2 cases), valvular disease (3 cases), WPW syndrome (1 case), aortic aneurysm (4 cases). The mean age was 66, ranged from 51 to 79. The simultaneous occurrence of the two lesions were observed in 6 cases and thoracic malignancy was diagnosed after a varying interval of time following surgery of cardiovascular disease in 4 cases. In cases of thoracic malignancy accompanied with heart disease, the treatment of heart disease should precede the operation of malignant disease to reduce the risk of surgery. For the patient with esophageal cancer, posterior mediastinal esophagostomy should be applied who may have heart surgery in future. In cases of coexisting malignancy and aortic aneurysm, the priority of treatment should be determined considering the size of aneurysm. If the transverse diameter of aneurysm is larger than 7 cm, there is a high risk of rupture, so surgery for the aneurysm precedes operation of malignant diseases. It is desirable to avoid concomitant operation of malignancy and cardiovascular disease.

Deep hypothermic circulatory arrest (DHCA) was introduced as an adjunct for operations involving aortic arch lesions in 1970's and has since been widely used. Profound hypothermia protects the brain and other vital organs by reducing metabolic rate. We initiated the use of continuous retrograde cerebral perfusion (CRCP) via the superior vena cava during DHCA in 1987. We studied 15 patients who required DHCA and CRCP during repair or replacement of the aortic arch. CRCP times ranged from 11 to 78 (mean +/- S.D.; 37.3 +/- 21) minutes, and minimal nasopharyngeal temperatures ranged from 13.7 to 25 (17.7 +/- 2.6) degrees C. Two patients died one month postoperatively due to preoperative disease. Three patients, who were in shock preoperatively due to cardiac tamponade, developed acute renal failure postoperatively. The remaining patients were weaned from the respirator by the 2nd postoperative day. No patient had CRCP-related complications. During CRCP, the partial pressure of oxygen (PO2), saturation of oxygen (SO2), and oxygen content significantly decreased (p < 0.001), and the partial pressure of carbon dioxide (PCO2) and CO2 content significantly increased (p < 0.001) between retrogradely perfused blood and blood draining from the arch vessels. These results most probably reflected that the aerobic metabolism of the brain was maintained by CRCP while the central nervous system was maintained in a hypothermic state, with oxygen and substrate availability, wash-out of metabolites, and buffering capacity and oncotic pressure of the blood maintained. This technique offers the potentials of sufficient metabolic support to the brain during DHCA and prolonged safe time limits of DHCA.

Nosocomial infection due to MRSA at the Kagoshima University Hospital and their coagulase typing were examined using S. aureus (349 strains) clinically isolated in 1989. The results were as follows: 1) S. aureus consisted of 43.6% of MRSA and 56.7% of Methicillin-sensitive S. aureus (MSSA). 2) MRSAs were recovered most frequently from the specimens from the respiratory tract (47.8%). 3) The isolation of MRSA gradually increased in frequency from January to August; however, that of MSSA did not show a similar tendency. 4) The isolation of MRSA was higher in frequency in the surgical wards, the ICU and the pediatric ward. 5) When classified into 8 coagulase types, MRSAs (133 strains) consisted of only 3 types (54.1% of type II, 32.3% of type VII, and 12.0% of type IV), whereas MSSAs contained all coagulase types. As compared with the results of coagulase typing at other institutions, the incidence of type VII was much more frequent at our hospital. 6) A few coagulase types of MRSA appeared in each ward. Also, type II MRSA strains increased in June and July, and type VII MRSA increased in August. However, MSSA strains did not show any similar tendency.

Susceptibility to antibiotics of 123 MRSA strains isolated at the Kagoshima University Hospital in 1989 was examined. The results were as follows: 1) Susceptibility of MRSA strains was excellent to VCM, MINO, and RFP, followed by IMP, CLDM, and CPFX. However, most strains were resistant to PCG, MPIPC, ABPC, CET, CMZ, CZON, GM, and AMK. 2) Five strains highly resistant to RFP were isolated. Three of these strains were isolated on the ward for tuberculosis. This suggests easy development of resistance to RFP by MRSA. 3) Differences in susceptibility to antibiotics between coagulase type II and type VII strains were examined. The cumulative percentage of type II strains susceptible to CLDM (MICs less than 0.5 microgram/ml) was 15.3%, and that of type VII was 45.2%. Strains resistant to CLDM were more frequently isolated among type II than among type VII strains (p less than 0.001). A similar relationship between strains and antibiotics was also found with EM and CPEX. On the other hand, the cumulative percentage of type II strains susceptible to AMK (MICs less than 25 micrograms/ml) was 89.7%, and that of type VII was 9.7%. Strains resistant to AMK were more frequently isolated among type VII than among type II strains (p less than 0.001).

Of 91 patients with prostatic cancer treated at our Department of Urology, from January 1976 through December 1987, 42 cases of stage D2 cancer treated with endocrine therapy were evaluated retrospectively with regard to clinical parameters and prognoses. The patients with marked increase in the level of the prostatic acid phosphatase (PACP), and the lactate dehydrogenase (LDH) in serum, and marked decrease in volume of hemoglobin (Hb) had a poor prognosis. The patients who took a long time to obtain a favorable response to the therapy had a poor prognosis. The response grade in NPCP criteria at 3 months after the initiation of therapy reflected the prognosis, and showed good correlation to the grade of favorable response.

The clinical efficacies of 10% lidocaine aqueous gel with and without 3% glycyrrhetinic acid 3-0 hemiphthalate disodium (GAHPh) applied as a skin patch for reduction of pain from venous cannulation were evaluated in a double blind study. Twenty-four adult patients, who were scheduled for surgery under general anesthesia, gave informed consent to participate in this study. The patients were allocated randomly into two groups: one for a dermal patch GAHPh (GAHPh group) and the other for a dermal patch without GAHPh (plain group). Approximately 0.3g of either gel with or without GAHPh, soaked in a round sponge (25mm in diameter, 1mm in thickness), was applied over the selected vein on the arm and was covered with an adhesive plastic film (Tegaderm). Pain score was graded by the number of painful spots out of the 5 tests in the treated skin area. In patients with a pain score under 1, venous cannulation was carried out without an intradermal injection of a local anesthetic and pain associated with the cannulation procedure was graded by patients on a scale of 5, where 0 = no pain, 1 = little pain, 2 = moderate pain, 3 = painful, 4 = very painful. The mean application time periods were 59.3 min for the GAHPh group and 60.3 min for the plain group. Transient local redness was observed in 8 patients after removal of the gels; 3 in the GAHPh group and 5 in the plain group. The mean pain score (1.3 +/- 1.5) in the GAHPh group, was significantly lower than that (2.5 +/- 1.7) in the plain group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)