General pharmacological profile of the novel cholecystokinin-A antagonist loxiglumide

The general pharmacological properties of a novel cholecystokinin-A antagonist, loxiglumide ((+/-)-4-(3,4-dichlorobenzamido)-N-(3-methoxypropyl)-N-pentylgl utaramic acid, CR 1505, CAS 107097-80-3) on central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems were investigated in experimental animals. 1. Central nervous system: At a dose of 30 mg/kg, i.v. loxiglumide showed ptosis in one of 6 mice, but at doses of 3 and 10 mg/kg, i.v. no change on gross behavior in mice. Loxiglumide had no effect on locomotor activity and thiopental-induced hypnosis, anti-convulsive activity, analgesic activity in mice and rectal temperature changes in rats. 2. Autonomic nervous system: In vitro, loxiglumide at concentrations of 10(-4) and 3 x 10(-4) mol/l slightly inhibited agonist-induced contractions in the isolated guinea pig ileum and spontaneous rhythmic contractions in the isolated non-pregnant rat uterus. But loxiglumide had no effect on oxytocin-induced contraction in isolated non-pregnant rat uterus. 3. Cardio-respiratory system: Loxiglumide had no effect on heart rate and electrocardiogram in anesthetized dogs. But it slightly increased blood pressure and decreased the frequency of respirations at a dose of 30 mg/kg, i.v. Furthermore, loxiglumide slightly decreased femoral arterial blood flow at doses of more than 3 mg/kg, i.v. On the other hand, it had no effect on contractile force or contraction rate in the isolated guinea pig atrium and resting tension in the isolated rabbit aorta. 4. Gastrointestinal system: Loxiglumide increased bile secretion at doses of 10 and 30 mg/kg, i.v. in anesthetized rats and at doses of 3, 10 and 30 mg/kg, i.v. in anesthetized dogs. However, total bile acid output was not affected by loxiglumide. On the other hand, loxiglumide had no effect on pancreatic secretion, gastric secretion and gastric emptying in rats and intestinal transport activity in mice. 5. Hematology: In vitro, in the case of samples without bovine serum albumin, at concentrations of more than 1.9 x 10(-3) mol/l loxiglumide showed hemolysis, while in the case of samples with bovine serum albumin, at concentrations of more than 6.9 x 10(-3) mol/l loxiglumide showed hemolysis, and its maximal potency was weak compared to albumin-free conditions. On the other hand, in vivo, loxiglumide had no effect on hemolysis. In addition, it had no effect on platelet aggregation, prothrombin time and activated partial thromboplastin time. 6. Miscellaneous pharmacological actions: Loxiglumide had no effect on local anesthetic activity in guinea pigs and renal function in mice. These results suggest that loxiglumide seems to produce no serious side effects on the central nervous system, autonomic nervous system, cardio-respiratory system, gastrointestinal system, hematological and miscellaneous systems at pharmacologically effective doses.     

Antiemetic efficacy of granisetron in pediatric cancer treatment--(2). Comparison of granisetron and granisetron plus methylprednisolone as antiemetic prophylaxis

A crossover clinical trial was carried out to compare the effectiveness and safety of granisetron alone (40 micrograms/kg) with that from a combination of granisetron plus methylprednisolone (MPL, 10 mg/kg) for control of emesis and vomiting induced by anticancer drugs in children with cancer. Complete control of emesis and vomiting were achieved in 95% (19/20 cases) of patients receiving the combination compared to 85% (17/20 cases) of patients receiving granisetron alone. There were no clinical toxicities or side effects in either treatment group. These data indicated that the combination of granisetron plus MPL was superior for control of emesis and vomiting in children receiving cytostatic anticancer drugs.     

Yield enhancement effects of boosted dual word-line (BDWL) schemefor high density DRAMs

This paper describes the yield enhancement effects of a boosted dual word-line (BDWL) scheme for the first Al wiring in high density DRAMs, with a defect density model and a yield model used for comparison with that of the commonly used word-shunt (WS) scheme. Additionally, the yield of first Al wiring with a step height between memory cell array and peripheral circuit regions is also estimated. The yield estimation demonstrated that the yield enhancement effect of the wide first Al wiring for the BDWL scheme was comparable with or surpassed that of the redundancy for the WS scheme yield, when the first Al wiring pitch over the memory cell array or a BDWL scheme was over 4 times wider than that of the WS scheme. The yield estimation with step height indicated that the first Al wiring yield of the BDWL scheme with the step height exceeded that of the WS scheme with the step height of zero, even if using some global planarization technology     

Loop recovery via ℋ︁∞-modified complementary sensitivity recovery for non-minimum phase plants

In order to recovery robust stability of a desirable state feedback system by output feedback, the desirable complementary function is approximated by a modified complementary function of the output feedback system by solving an ??^∞ norm-minimization problem. The modified complementary function is obtained by getting rid of non-minimum phase factors from the complementary function. Numerical examples show the superiority of this method to LQG/LTR method and other methods.     

Long-term results of preoperative hyperthermo-chemo-radiotherapy (HCR) for patients with esophageal carcinoma invading neighboring structures (T4)

PATIENTS: A total of 180 patients with esophageal carcinoma invading the neighboring structures (T4) were surgically treated by esophagectomy and reconstruction in the Department of Surgery II, Kyushu University from January 1965 to April 1997. Any of these cases with distant node metastasis and demonstrating organ metastasis or a combined resection of adjacent structures were excluded from this study. As a result, twenty-six patients treated with preoperative hyperthermo-chemo-radiotherapy (HCR Group), 39 treated either with preoperative radiotherapy or preoperative chemo-radiotherapy (R or CR Group) and 23 non-treated patients (Non-tx Group) were thus entered in this study. RESULTS: The 3-year survival rates after esophagectomy in HCR Group, R or CR Group and Non-tx Group were 26.5%, 0% and 9%, respectively, while the 5-year survival rate of the HCR group was 15.9%. The group with preoperative HCR thus showed a significantly more favorable outcome than R or CR Group and Non-tx Group. (p < 0.05). DISCUSSION: The significant difference observed in the prognosis was thought to be due to the reinforced effect of local regulation due to hyperthermia. Our data thus suggest that preoperative HCR contributes to the prolonged post-operative survival for carcinoma of the esophagus invading the neighboring structures.     

Syntheses and properties of surfactants containing organometals: IV. Organo silicone

The authors synthesized nonionic surfactants containing dimethylpolysilane, dimethylpolysilmethylene and dimethylopolysiloxane as the hydrophobic groups, and investigated their surface activities. In their ability to lower the aqueous surface tension, the polysiloxane surfactants were the most active, and there is little reason to choose between the other two kinds of surfactants. With regard to the ability of lowering the interfacial tension between water and silicone oil, the polysilmethylene surfactants were most effective when the concentration of aqueous solution was below 0.5 wt %. Above this concentration, however, the polysiloxane surfactants were superior. Also investigated was the lowering of surface tension of nonaqueous polyols and their ability to wet low energy hydrophobic surfaces such as polyethylene.     

ℓ2 Gain Estimation and Visualization of A Control Parameter Set in 3D Space Using Plant Response Data

In this paper, a novel parameter space approach that uses volume rendering is proposed to visualize controller parameter sets that consist of three controller parameters. An off‐line design method for robust control using plant response data is also studied. A solution set with equal ?₂ gain can be visualized as isosurfaces in three‐dimensional space, and the designer can visually select an appropriate parameter. This numerical method is applicable to many practical specifications, in contrast to analytical methods based on solving equations. An estimation method based on the extension theorem and a method using bandpass filters are both considered as possible methods for estimating the ?₂ gain of the sensitivity functions when using grid points on the order of tens of thousands to create the volume data.The former method is superior to the latter with respect to accuracy but impractical with respect to computational load. The latter method is hence practical, because the computing time is reduced to less than 0.05 s for about 300,000 grid points by parallel computation with a graphical processing unit.     

L1 synthesis of a static output controller for positive systems by LMI iteration

An approach to find a static output feedback gain that makes the feedback system positive and minimizes the L₁ gain is proposed. The problem of finding a static output feedback gain has 3 aspects: stabilizing the system, making the system positive, and then minimizing the L₁ gain. Each subproblem is described by bilinear matrix inequality with respect to the feedback gain and the Lyapunov matrix or vector. Linear matrix inequality (LMI) that is sufficient to satisfy bilinear matrix inequality is derived using a convex‐concave decomposition, and the feedback gain sequence is calculated by an iterative solution of LMI. The sequence of the upper bounds on the design parameter is guaranteed to be monotonically nonincreasing for each algorithm. Similarly, 2 other LMIs are derived for each subproblem using another convex‐concave decomposition and PK iteration. The effectiveness of these algorithms is illustrated via several numerical examples.     

Pressure dependence of upper critical solution temperatures in the polystyrene - cyclohexane system

The pressure dependence of the upper critical solution temperature $\text{(}\text{d}\text{T}\text{d}\text{p}\text{)}{}_{\mathrm{c}}$ in the polystyrene-cyclohexane system has been measured over the pressure range of 1 to 50 atm. The value of $\text{(}\text{d}\text{T}\text{d}\text{p}\text{)}{}_{\mathrm{c}}$ determined over the molecular weight (M_w) range of 3.7 × 10⁴ to ～145 × 10⁴ greatly depends on the molecular weight of polystyrene. The value of $\text{(}\text{d}\text{T}\text{d}\text{p}\text{)}{}_{\mathrm{c}}$ for a polystyrene solution of low molecular weight (M_w = 3.7 × 10⁴) is positive (3.14 × 10^?3 degree atm^?1), while the values are negative (?0.52 × 10^?3～?5.64 × 10^?3 degree atm^?) for solutions of polystyrene over the high molecular weight range of 11 × 10⁴ to ～145 × 10⁴. The Patterson-Delmas theory of the corresponding state and the newer Flory theory have been used to explain this behaviour.