Combined use of phenoxybenzamine and dopamine for low cardiac output syndrome in children at withdrawal from cardiopulmonary bypass.

The combined use of phenoxybenzamine and dopamine was applied in infants and children when it was difficult to come off cardiopulmonary bypass for low cardiac output. The rationale of this method is to prevent the alpha-adrenergic action of dopamine by phenoxybenzamine and to encourage the beta-adrenergic and direct specific action of dopamine. Dopamine was used in dosage of 10 to 30 micrograms/kg per min after the additional administration of a half of the initial dosage of phenoxybenzamine; this was infused by drip always in a dosage of 0.5 to 1.0 mg/kg during the first half of cardiopulmonary bypass. It was possible to come off cardiopulmonary bypass with a stable haemodynamic state (mean arterial pressure more than 60 mmHg and total peripheral vascular resistance less than 2000 bynes s cm-5) and a good urinary output.     

Current evidence of irinotecan combination chemotherapy with TS-1 in patients with advanced colorectal cancer

A combination of irinotecan (CPT-11) with continuous intravenous infusions of (infusional) 5-fluorouracil (5-FU) and Leucovorin (LV) is one of the standard treatments for advanced colorectal cancer patients. However, recent concerns about safety and convenience have prompted the development of new oral fluoropyrimidine derivatives and improved regimens. TS-1, the oral fluoropyrimidine widely used in the treatment for gastric cancer, was approved for advanced colorectal cancer. Recently, several phase I/II studies assessed the efficacy and safety of combined treatment with TS-1 plus CPT-11 in patients with advanced colorectal cancer. These results showed that TS-1 plus CPT-11 was very effective. Toxicity was generally mild and manageable on an outpatient basis. Current evidence showed that a combination of CPT-11 plus TS-1 was more convenient and easier to administer than a combination of CPT-11 plus infusional 5-FU and LV. It is essential to prove that the combination of TS-1 plus CPT-11 can replace the combination of infusional 5-FU and LV plus CPT-11 without negatively affecting efficacy and toxicity.     

The current evidence of S-1 and irinotecan hydrochloride combination chemotherapy with tri-weekly schedule

A combination therapy of irinotecan hydrochloride (CPT-11) with continuous intravenous infusions of (infusional) 5-fluorouracil (5-FU) and Leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns on safety and convenience have prompted the development of new oral fluoropyrimidine derivatives which improved regimens. Yamada et al conducted a phase I study to assess the maximum tolerated dose and recommended dose of S-1 combined with CPT-11. The study recommended that 150 mg/m2 of CPT-11 be given on day 1 and 80 mg/m2 of S-1 daily on days 1 to 14 every 3 weeks. Recently, several phase I/II studies assessed the efficacy and safety of the combined therapy with S-1 and CPT-11 in patients with advanced colorectal cancer. Some of the studies which were ongoing assessed a tri-weekly schedule regimen. Our results showed that S-1 plus CPT-11 was very effective, with a response rate of 63% and PFS of 8 months. Toxicity was generally mild and manageable on an outpatient basis. The current evidence showed that a combination of S-1 and CPT-11 was more convenient and easier to administer than a combination of CPT-11 plus infusional 5-FU and LV. It will be essential to prove that the combination of S-1 plus CPT-11 can replace the combination of infusional 5-FU and LV plus CPT-11 without negatively affecting efficacy and toxicity.     

Performance of polysulfone membrane dialyzers and dialysate flow pattern

Background It is important to observe the flow pattern of dialysate when evaluating dialyzer function and developing the most appropriate design. We investigated dialysate flow through two polysulfone membrane dialyzers (TS-UL [Toray Medical] and APS-S [Asahi Medical]) by computed tomography (CT), with barium sulfate as the contrast medium. We also performed a clinical comparison of these two dialyzers. Methods For the in vitro experiment, after confirming the steady-state flow of mock blood (xanthan gum solution; 200 ml/min) and dialysate (500 ml/min), fresh dialysate, containing 5% (w/v) barium sulfate was perfused, and longitudinal CT scans of the dialyzer were obtained. Then the concentration of barium sulfate was measured (in Hounsfield units) in three fixed regions of interest. For the in vivo experiment, 12 patients on stable hemodialysis who had been using the APS-S for more than 1 month were switched to the TS-UL for 1 month and changes in various parameters were assessed. Results The distribution of dialysate was homogeneous on CT scans of the TS-UL, but not on scans of the APS-S. The dialysate concentration curves for the three regions of interest were similar with the TS-UL, but not with the APS-S. Clearance of urea nitrogen and albumin loss were both significantly higher with the TS-UL than with the APS-S. The decrease in alpha 1-microglobulin was larger with the TS-UL than with the APS-S, but not significantly. Conclusions Clearance of substances over a wide range of molecular weights was higher with the TS-UL than with the APS-S, and differences in the design of the dialysate compartment may have been involved in this feature.     

Dependence of reaction times on movement patterns in patients with cerebral hemiparesis

Premotor times (PMTs) of both biceps muscles in flexion and supination of the forearms were examined in 10 left- and 16 right-hemiparetic patients, and 11 control subjects. Compared with the control group, the difference of PMTs between flexion and supination was small both in the affected and the non-affected sides of the left hemiparetic group, and only in the affected side of the right hemiparetic group. These findings suggest that the right hemisphere has a dominant role for the programming of the movement patterns in the initiation of rapid movements such as simple reaction time tasks.     

Pharmacological studies on the clathrate compound of mobenzoxamine with beta-cyclodextrin. (I). Effects on the digestive system

Effects of the clathrate compound of mobenzoxamine (MBX) with beta-cyclodextrin (MBX-CD), a new gastro-intestinal function modulator, on the digestive system were studied in comparison with those of metoclopramide, domperidone and trimebutine. MBX-CD showed inhibitory effects that were approximately 1/4 times as potent as metoclopramide on both apomorphine- and copper sulfate-induced emesis and about 1/40 times as potent as domperidone on apomorphine-induced emesis in dogs. In rats, MBX-CD enhanced gastric emptying as potently as metoclopramide, and only MBX-CD showed a clear amelioration of the delayed gastric emptying induced by BaCl2. Similarly, only MBX-CD showed an ameliorative effect on small intestinal transport accelerated by BaCl2 in mice. Though both MBX and trimebutine inhibited spontaneous contractions of the isolated guinea pig stomach and rabbit intestine, it seemed that the properties of these effects were different from those of papaverine. On isolated guinea pig ileum, MBX inhibited contractions induced by various agonists equally to or more potently than trimebutine or papaverine. The results suggest that MBX-CD or MBX acts extensively on the gastro-intestinal system for the reason that it has not only the respective properties of the gastro-intestinal function modulators used as the standards, but also its own characteristic effects.     

Diagnostic Approach to Autoimmune Blistering Diseases Using Immunoblotting with Chemiluminescence

Autoantibodies in sera from patients with autoimmune blistering diseases were detected by immunoblotting with chemiluminescence. This method provided the high sensitivity in the detection of autoantibodies against human epidermal extract. It was useful for detecting low titers of autoantibodies, and identifying small amounts of autoantigens in antigen extracts.     

In vivo effects of bacterial lipopolysaccharide on proliferation of macrophage colony-forming cells in bone marrow and peripheral lymphoid tissues

Changes in the number of macrophage colony-forming cells in various tissues of mice injected with lipopolysaccharide (LPS) from Klebsiella pneumoniae, Escherichia coli, or Salmonella enteritidis were studied. The injection of LPS increased macrophage colony-forming cells in peripheral lymphoid tissues such as the spleen, mesenteric lymph nodes, and regional lymph node, although the same treatment caused the decrease of such cells in the bone marrow. This phenomenon was consistently observed when tested by various LPSs. The injection of LPS into mice which had been exposed to X-ray irradiation and reconstituted with syngeneic normal bone marrow cells decreased colony-forming cells in the spleen. The increase of macrophage colony-forming cells in the spleen seemed, therefore, not to be due to migration from the bone marrow. The injection of LPS appeared to shorten the lag time before the initiation of mitosis of colony-forming cells in the spleen but not in the bone marrow. No participation of serum factors in this phenomenon could be detected. It was suggested that there might be an essential difference between the responsiveness to LPS of macrophage colony-forming cells in the spleen and those of the bone marrow.     

Prolonged nitric oxide inhalation fails to regress hypoxic vascular remodeling in rat lung

STUDY OBJECTIVE: The purpose of present study was to investigate whether long-term nitric oxide (NO) inhalation during the recovery in air might improve the regression of chronic hypoxic pulmonary hypertension (PH) and vascular changes. MATERIALS AND METHODS: The rats were exposed to 10 ppm of NO in air for 10 days (n = 12) and 30 days (n = 4), or 40 ppm of NO in air for 10 days (n = 6) and 30 days (n = 12) following 10 days of hypobaric hypoxia (380 mm Hg, 10% oxygen). For each NO group, air control rats following hypoxic exposure were studied at the same time (n = 13, 11, 9, and 11, respectively). Normal air rats (n = 6) without hypoxic exposure and rats (n = 7) following 10 days of hypoxic exposure were used as normal and chronic hypoxic control groups, respectively. Muscularization of normally nonmuscular peripheral arteries and medial hypertrophy of normally muscular arteries were assessed by light microscopy. An additional 16 rats were used to investigate the recovery of pulmonary artery pressure with (n = 8) and without NO inhalation (n = 8) after 10 days of hypobaric hypoxia. RESULTS: Long-term hypoxia-induced PH, right ventricular hypertrophy (RVH), and hypertensive pulmonary vascular changes, each of which regressed partly after recovery in room air. There were no differences among rats with and without NO during each recovery period in RVH, medial wall thickness of muscular artery, and the percentages of muscularized arteries at the alveolar wall and duct levels. Continuous inhaled 40 ppm NO decreased pulmonary artery pressure from 40.1 +/- 1.1 to 29.9 +/- 3.8 mm Hg (mean +/- SE) [n = 8], which was not different in the rats without NO inhalation (n = 8). Urine nitrate level was higher in rats that had inhaled NO. CONCLUSION: Continuous NO inhalation showed no effect on regression of pulmonary vascular remodeling in chronic hypoxic PH after returning to room air.