Natural frequency/damping coefficient relationship of the catheter-manometer system required for high-fidelity measurement of the pulmonary arterial pressure

Using a digital simulation method, we analyzed the relationship between natural frequency (f _n ) and damping coefficient () of the catheter-manometer system required for high-fidelity measurement of the pulmonary arterial pressure. The pulmonary artery pressure waveform was obtained with a catheter-tip transducer and it was fed into a dynamic simulator programmed on a computer. The original waveform and the output of the simulator were compared and judged visually for the fidelity. From this analysis, the combination of f _n and was obtained and was plotted on a f _n – diagram. It showed as an area, which was convex on the left side and open on the right side. The left-convex endpoint was located at a damping coefficient of about 0.7. At a lower heart rate, this area was extended to the lower frequency side, while, at a higher heart rate, this area was limited to the higher frequency side. The f _n – diagram was also constructed theoretically by calculating the relations between natural frequencies and damping coefficients of a second order system with the amplitude and phase error tolerance set at +/–5% respectively.(Kinefuchi Y, Suzuki T, Takiguchi M, et al.: Natural frequency/Damping coefficient relationship of the catheter-manometer system required for high-fidelity measurement of the pulmonary arterial pressure. J Anesth 7: 419--426, 1993)     

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Dependence of the Molecular Mobility and Protein Stability of Freeze-Dried γ-Globulin Formulations on the Molecular Weight of Dextran

Purpose. The effect of the molecular weight of dextran on the molecular mobility and protein stability of freeze-dried serum -globulin (BGG) formulations was studied. The stabilizing effect of higher molecular weight dextran is discussed in relation to the molecular mobility of the formulations. Methods. The molecular mobility of freeze-dried BGG formulations containing dextrans of various molecular weights was determined based on the free induction decay of dextran and water protons measured by proton NMR. The protein stability of the formulations was determined at temperatures ranging from 20 to 70°C by size exclusion chromatography. Results. Changes in the molecular mobility of freeze-dried formulations that occurred at temperatures below the glass transition temperature could be detected as the molecular mobility-changing temperature (T_mc), at which dextran protons started to exhibit a Lorentzian relaxation decay due to higher mobility in addition to a Gaussian relaxation decay. T_mc increased as the molecular weight of dextran increased. The proportion of dextran protons which exhibited the higher mobility relaxation process (P_hm) at temperatures above T_mc decreased as the molecular weight of dextran increased. Protein stability was closely related to molecular mobility. The temperature dependence of the denaturation rate changed at around T_mc, and denaturation in the microscopically liquidized state decreased as P_hm decreased with increasing molecular weight of dextran. Conclusions. The effect of the molecular weight of dextran on the protein stability of freeze-dried BGG formulations could be explained in terms of the parameters obtained by ¹H-NMR such as T_mc and P_hm. These parameters appear to be useful in preformulation and stability prediction of freeze-dried formulations.     

Direct tumor growth suppressive effect of melanoidin extracted from immunomodulator-PSK

Melanoidin, which belongs to the melanin group of molecules, was extracted from the polysaccharide biological response modifier PSK. Melanoidin was cultured together with HCT-15 cells derived from human colon cancer and with AGS cells derived from human gastric carcinoma. After four days of culture, cell count was compared with that of the control cells. Significant suppression was observed, that is, 50% suppression was shown at concentrations of melanoidin between 200 and 100 micrograms/ml. A histogram generated by flow cytometry showed elevation of the tetraploid peak and of that between diploid and tetraploid peaks, suggesting blockage of S phase and G2 to M phase of the cell cycle. Thus, melanoidins contained in the immunomodulator PSK revealed to have a direct tumor cell growth inhibitory effect.     

A rapid method for detecting barbiturates in serum using EI-SIM

A simple and rapid method for analysis of barbiturates in serum has been developed. In order to extract and clean barbiturates in serum, a separation column packed with Extrelut and Florisil was used, and the eluate was directly analyzed by means of electron impact selected ion monitoring (EI-SIM). Selected ions used were base peak ions of 10 barbituartes, and the internal standard used was allobarbital or secobarbital. The calibration curves were linear over the range 0.5–5 ng. Extraction of replicate serum samples containing 20 g/1.5 ml and 5 g/1.5 ml resulted in a recovery of 87.2–105.2% and 81.6–104.6%, respectively, with the exception of phenobarbital, which was 151.9% and 172.1%, respectively. Secobarbital was also analyzed in the serum of 13 patients who had been given secobarbital intravenously. In 3 out of 10 cases, Secobarbital levels greater than 1 g/ml were detected more than 72 h after administration. This method seems to have possibilities for clinical use.Paper presented at the 2nd International Symposium ADVANCES IN LEGAL MEDICINE, Berlin, Germany, August 30–September 1, 1993     

Protective effects of an aged garlic extract on doxorubicin-induced cardiotoxicity in the mouse

Protective effects of an aged garlic extract on the cardiotoxicity of doxorubicin (DOX) was evaluated using the mouse. DOX (1.5 mg/kg body wt i.p.) was administered three times per week for 40 days. An aged garlic extract, WG-1 (a preserved stock solution; Wakunaga Pharmaceutical) was administered intraperitoneally six times weekly. DOX caused changes in the electrocardiogram. In the control mice, the width of the QRS complex was 20 +/- 2.8 milliseconds, the R-R interval was 130 +/- 2.8 milliseconds, and the P-Q interval was 30 +/- 1.4 milliseconds. In mice treated with DOX for 40 days, the width of the QRS complex was 50 +/- 10 milliseconds (p < 0.05), the R-R interval was 240 +/- 30 milliseconds (p < 0.05), and the P-Q interval was 45 +/- 1.0 milliseconds (p < 0.01). These values were significantly smaller in mice treated with WG-1 + DOX than in mice treated with DOX. The width of the QRS complex was 29.3 +/- 5.8 milliseconds (p < 0.05), the R-R interval was 145.8 +/- 17.9 milliseconds (p < 0.01), and the P-Q interval was 37.8 +/- 3.5 milliseconds (p < 0.05). The lipid peroxidation in the heart homogenates prepared from DOX-treated mice, as measured by thiobarbituric acid-reactive substance (TBARS, nmol malondialdehyde/100 mg protein) was 332.5 +/- 67.0, which was significantly larger than that in the control mice (186.6 +/- 42.2) (p < 0.05). WG-1 decreased the level of TBARS in DOX-treated mice significantly. In the mice treated with WG-1 + DOX, TBARS was 221.3 +/- 31.6, which was significantly smaller than that of DOX-treated mice (p < 0.05). Histological study demonstrated that the heart treated with DOX had vacuolization in muscle cells, disrupted myofibrils, and swollen mitochondria. Mice that received WG-1 + DOX had no significant pathological lesions in the heart.     

Physical Stability and Protein Stability of Freeze-Dried Cakes During Storage at Elevated Temperatures

The relationship between physical stability of freeze-dried cakes and protein stability during storage was studied using -galactosidase as a model protein and inositol as an excipient. Amorphous samples freeze-dried from solutions containing the enzyme and various concentrations of inositol in sodium phosphate buffer (50 mM, pH 7.4) were stored for 7 days over P₂O₅ at 40 to 70°C. Structural collapse and inositol crystallization were observed in some of the samples, depending on the formulation and storage temperature. The physical stability of freeze-dried samples was also studied by differential scanning calorimeter (DSC). Inositol showed a protein-stabilizing effect when its amorphous form was retained during storage, regardless of structural collapse. However, crystallization of inositol during storage removed its stabilizing effect. Addition of water-soluble polymers such as dextran, Ficoll and carboxymethyl cellulose sodium salt (CMC-Na) preserved activity of the enzyme by preventing inositol crystallization.     

The effects of oligomers content and surface morphology on foreign-body tumorigenesis with polyetherurethanes: two years subcutaneous implantation study in rats

Three polyurethane materials were prepared by removing and adding the leachable oligomers from and to the same polyetherurethane (PEU). The three PEU materials were dissolved in tetrahydrofuran (THF) and dimethyformamide (DMF) and the solutions were cast on a glass plate to make films of smooth and foamed surfaces, respectively. These six materials and polydimethylsioxane (silicone) were implanted into subcutaneous pocket of rats for 2 years to evaluate the long-term effects around the implant. Among the smooth surface implants, PEU materials induced a higher incidence of tissue responses, including tumor formation than silicone. However, no relationship between the oligomer content and the tissue responses was found. Changing surface morphology from a smooth to a foamed one prolonged the latent period of tumor development and decreased the total tumor incidence.     

Estimation of physiologic ability and surgical stress (E-PASS) as a new prediction scoring system for postoperative morbidity and mortality following elective gastrointestinal surgery

(Received for publication on Oct. 25, 1997; accepted on July 7, 1998)