Biological characteristics of lactosaminated N-succinyl-chitosan as a liver-specific drug carrier in mice

Lactosaminated N-succinyl-chitosan (Lac-Suc) was prepared by reductive amination of N-succinyl-chitosan (Suc) and lactose using sodium cyanoborohydride. Six-day reaction using lactose (12.8-fold (w/w)) yielded Lac-Suc with lactosamination degree of 30% (mol/sugar unit). Fluorescein thiocarbamyl-Lac-Suc (Lac-Suc-FTC) was prepared by labeling Lac-Suc with fluorescein isothiocyanate. Lac-Suc-FTC was injected intravenously at a dose of either 1 (high dose) or 0.2 (low dose) mg/mouse. At both doses, Lac-Suc-FTC initially underwent fast hepatic clearance, showed maximum liver localization at 8 h, and the amounts localized there were maintained even at 48 h post-injection. Very slow excretion into feces and urine was observed. The ratio of liver AUC_{0–48 h} to plasma AUC_{0–48 h} at low dose was three times higher than that at high dose. On the other hand, the Suc derivative, Gal-Suc, obtained by reductive amination of Suc/galactose showed very little distribution to the liver similarly to Suc itself. Further, since the liver uptake of Lac-Suc-FTC was inhibited by asialofetuin, it was suggested that the liver distribution of Lac-Suc should be concerned with asialoglycoprotein receptor. Thus, Lac-Suc was found available as a carrier exhibiting a high affinity to and long retention in the liver.     

Importance of dissolution process on systemic availability of drugs delivered by colon delivery system

The relationship between in vitro drug release characteristics from colon delivery systems and in vivo drug absorption was investigated using three kinds of delayed-release systems. 5-aminosalicylic acid (5-ASA), tegafur (FT) and carbamazepine (CBZ) were selected as model drugs. Pressure-controlled colon delivery capsules (PCC) for liquid preparations, time-controlled colon delivery capsules (TCC) for liquid and solid preparations and Eudragit S coated tablets for solid preparations were used in this study. At first, in vitro dissolution tests for all preparations were performed. Drug release from solid preparations was delayed compared to that from liquid preparations with all three drugs. Next, these preparations were administered to fasted beagle dogs. For 5-ASA, the mean C_maxs (peak level) of Eudragit S coated tablets and PCC were 5.52 and 16.89 μg ml⁻¹, respectively. The mean T_maxs (time when drug reached peak level) were 3.0 and 5.3 h. AUCs were 22.57 and 48.09 μg·h ml⁻¹, respectively. For FT, C_maxs of Eudragit S coated tablet and PCC were 0.87 and 1.46 μg ml⁻¹, and T_maxs were 7.0 and 6.7 h, respectively. AUCs were 9.73 and 15.55 μg·h ml⁻¹ and bioavailabilities were 43.79 and 70.84%. For CBZ, the mean C_maxs of liquid preparations and solid preparations were 0.37 and 0.22 μg ml⁻¹, respectively. The mean T_maxs were 4.7 and 4.3 h. AUCs were 0.673 and 0.392 μg·h ml⁻¹. With liquid preparations, drug was thought to contact to the colonic membrane easily because of lack of interference by stools, and to be absorbed well as compared with solid preparations. From these findings, drug release from colon delivery systems and drug dissolution in the colonic lumen are very important factors for the systemic availability of drugs from the colon delivery systems.     

Effects of N-acetylcysteine in endotoxic shock

: The release of oxygen-free radicals has been implicated in both peripheral vascular and myocardial alterations of septic shock. N-Acetylcysteine (N-AC), a substrate for the production of glutathione, has potent antioxidant effects. As a nitrosothiol, it may also improve capillary blood flow. We studied the effects of N-AC in a dog model of endotoxic shock.

: Ten pentobarbital-anesthetized, mechanically ventilated dogs were randomly assigned to receive either N-AC (150 mg/ kg loading dose in 1 hour, followed by 20 mg/kg · h maintenance dose) or D5W. After the loading dose, each dog received 3 mg/kg Escherichia coli endotoxin intravenously. After 30 minutes, saline infusion was started to restore and maintain baseline filling pressures.

: The loading dose of N-AC increased Do₂ significantly (from 661 ± 54 to 914 ± 190 mL/min, P < .05), but Vo₂ remained stable. After the administration of endotoxin, fluid challenge restored cardiac output to baseline, in both groups. Hemoglobin and, thus, Do₂ were slightly lower in the N-AC-treated dogs, but Vo₂ was similar in both groups. At the end of the study, O₂ER was significantly higher in the N-AC-treated dogs than in the control dogs. Blood lactate levels fell more rapidly in the N-AC dogs than in the control dogs. Blood lactate levels returned to normal in the N-AC dogs but not in the control dogs. Tumor necrosis factor (TNF) also decreased significantly in the N-AC dogs but remained elevated in the control dogs.

: These data indicate that N-AC administration in endotoxic shock is well tolerated, may increase oxygen availability to the tissues, and is associated with an attenuation of TNF release.     

Dendrimer-mediated transdermal delivery: enhanced bioavailability of indomethacin

The transdermal delivery of aqueous formulations of indomethacin, a model drug, with different concentrations of three types of dendrimer showed a linear increase in flux with increasing concentration of each of the dendrimers. This result was in contrast to phase solubility studies, where Higuchi’s A_N profile was observed. The steady-state flux of the drug increased significantly and was highest with the G4-NH₂ dendrimer at 0.2% w/v concentration, which showed an enhancement factor of 4.5 compared to the pure drug suspension. In vivo, a steady-state flux was achieved in 5 h, and the C_max values were significantly higher with G4-NH₂ and G4-OH dendrimer formulations. The [AUC]_0–24h of G4-NH₂ (2.27 times) and G4-OH (1.95 times) formulations were significantly higher than that of the pure drug, but was only marginally higher in the case of G-4.5 dendrimer formulation. The % inhibition of paw volume showed a trend comparable to the pharmacokinetic data and a maximum of 1.6- and 1.5-fold increase was found with G4-NH₂ and G4-OH formulations, respectively, compared to the pure drug suspension.     

Dose-response study of metoclopramide in gastroesophageal reflux in infancy

Summary— Twenty-four infants, 1 to 18 months-old, who were referred to four centers for suspected gastroesophageal reflux and whose esophageal pH after a standard formula meal given at 9 to 10 am (Ho-day 1) fulfilled the criterion of being < 4 for more than 5% of the time between H₁ and H₆, entered a double-blind placebo-controlled dose-response trial of metoclopramide (M). Twenty-four hours later (day 2), patients were randomly assigned to receive either placebo or a single 0.1, 0.2, or 0.4 mg/kg dose of metoclopramide, 30 min before the formula meal ( n = 6/group) and the procedure was repeated. Metoclopramide plasma concentration was measured 1 h after dosing (C_1h). On day 1, the time during which the esophageal pH was < 4 (time pH < 4), and five other parameters, were not significantly different in the treatment groups. On day 2, time pH < 4 (m(SD)) decreased from 33(13) to 30(33), 39(27), to 36(47), 42(15) to 18(13) and 48(25) to 31(46) min in the placebo, 0.1, 0.2, and 0.4 mg/kg metoclopramide groups, respectively. Possibly due to the large interindividual variability, no significant differences in parameters were observed between the different groups. None of the parameters correlated with the metoclopramide dose. Time pH < 4 expressed as the difference between day 1 and day 2, relative to day 1, decreased significantly as a function of C_1h. No side effects were observed. A similar study should be performed after repeated dosing regimen.     

Conjugation of an antibody to cross-linked fibrin for targeted delivery of anti-restenotic drugs

There is an urgent need to treat restenosis, a major complication of the treatment of arteries blocked by atherosclerotic plaque, using local delivery techniques. We observed that cross-linked fibrin (XLF) is deposited at the site of surgical injury of arteries. An antibody to XLF, conjugated to anti-restenotic agents, should deliver the drugs directly and only to the site of injury. An anti-XLF antibody (H93.7C.1D2/48; 1D2) was conjugated to heparin (using N-succinimidyl 3-(2-pyridyldithio)propionate), low molecular weight heparin (LMWH) (adipic acid dihydrazide) and rapamycin (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide), and the conjugates purified and tested for activity before use in vivo. Rabbits had their right carotid arteries de-endothelialised and then given a bolus of 1D2–heparin, 1D2–LMWH or 1D2–rapamycin conjugate or controls of saline, heparin, LMWH, rapamycin or 1D2 (±heparin bolus) and sacrificed after 2 or 4 weeks (12 groups, n=6/group). Rabbits given any of the conjugates had minimal neointimal development in injured arteries, with up to 59% fewer neointimal cells than those given control drugs. Rabbits given 1D2–heparin or 1D2–LMWH had an increased or insignificant reduction in luminal area, with positive remodelling, while the medial and total arterial areas of rabbits given 1D2–rapamycin were not affected by injury. Arteries exposed to 1D2–heparin or 1D2–rapamycin had more endothelial cells than rabbits given control drugs. Thus, XLF-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall, where the conjugates can influence remodelling, re-endothelialisation and neointimal cell density, with reduced neointimal formation.     

Measurement of corticoids in the patients with clinical features indicative of mineralocorticoid excess

Background: A method for the measurement of five important serum and urinary corticoids on the syndrome of mineralcorticoid excess is reported. The methodology was combined gas chromatography-mass spectrometry (GC-MS) with selected ion-monitoring mode. Methods: After extraction with a solid-phase cartridge using an Oasis HLB copolymer, the residues were derivatized with a mixture of N-methyl-N-trimethylsilyltrifluoroacetamide/ammonium iodide/dithioerythritol (1000:4:5, v/w/w), and analyzed. Results: The linearity as the regression coefficients were >0.979 over a range of 1–500 ng/ml, and limit of detection ranged from 1 to 3 ng/ml while their analytical recoveries varied in the range of 75.7–94.9%. The overall precision (% CV) of the method were 3.2–7.2% and 3.6–6.3% for serum and urine, respectively. The accuracy expresses as % bias ranged from −4.1 to 6.4%. This assay was used on two patients with hypokalemic hypertension, and may be useful in ruling out mineralcorticoid excess (AME) type 1 or 2. Conclusions: The present GC-MS technique may be useful to differentiate between the syndrome of AME and other hypertensive diseases with clinical features suggestive of mineralcorticoid excess because of the assay's reliablity and precision.     

pH-Induced solubility transition of sulfonamide-based polymers

As an approach to designing new pH-sensitive polymers for bio-related application, we have modified selected sulfonamides, with various pK_a, to polymerizable monomers. The pK_a of the monomers, homopolymers, and copolymers with N,N-dimethylacrylamide were examined, and pH-induced phase transition behavior, particularly in solubility, was investigated. The pK_a of sulfonamide monomers and polymers at 25 °C was slightly higher than those of corresponding sulfonamides but the enthalpy of the ionization was influenced due to interfering resonance structures that are present in the mother compounds. The solubility transition of each homopolymer in aqueous solutions occurred at a degree of ionization of 85–90%. For the copolymers, the solubility transition observed by light transmittance completed in a narrow pH range (0.2–0.3 pH units) and this transition pH shifted to a higher pH region with the increasing sulfonamide unit in the copolymer, though the pK_a was not considerably changed. This polymer precipitation occurs because of the relative balance of overall hydrophilicity/hydrophobicity along the polymer chain. Because the unionized form of sulfonamide units is considered to be hydrophobic, the copolymer with higher content of sulfonamide unit requires a higher degree of ionization for solubilization and thus solubility transition occurred at higher pH.     

Addition of ketamine to propofol–fentanyl anaesthesia can reduce post-operative pain and epidural analgesic consumption in upper abdominal surgery

The aim of this study was to confirm whether intravenous anaesthesia supplemented with the N-methyl- -aspartate (NMDA) antagonist ketamine could reduce post-operative pain after elective open cholecystectomy. Fifty patients were randomised double-blind to one of the following two groups: PF Group received propofol and fentanyl supplemented with saline infusion; PFK Group received propofol and fentanyl supplemented with ketamine (total dose 2 mg/kg). During the first 48 post-operative hours, epidural analgesia was provided for all patients with patient-controlled epidural analgesia (PCEA) using 0.125% bupivacaine and morphine (0.05 mg/ml). Pain assessments at rest and movement, and cumulative PCEA volume consumed, were recorded at 5, 24 and 48 h post-operatively. The visual analogue scale (VAS) scores at rest were significantly less in the PFK Group than in the PF Group at 5, 24 and 48 h (P<0.001, P<0.001 and P=0.02, respectively). The VAS score at movement were also significantly (P<0.001) less throughout this study than in the PF Group. The difference in PCEA analgesic consumption at 0–5 and 5–24 h reached statistical significance (P<0.001 and P=0.008, respectively). Our results show that an intra-operative ketamine dose provides advantages for post-operative analgesia beyond its duration of action after an open cholecystectomy.     

Quantitative measurements of second harmonic Doppler using ultrasound contrast agents

Quantitative measurements of second harmonic and first harmonic Doppler were carried out using two ultrasound contrast agents, Albunex^® and FS069. The RMS amplitudes of the Doppler shift spectra were measured as a function of the concentration of the agents, frequency and transmitted acoustic pressure. The results showed that, for a given lot of contrast agent investigated, FS069 was able to produce higher levels of first and, especially, second harmonic signals compared to Albunex. Under the same experimental conditions, the RMS Doppler amplitude (RDA) of FS069 was 3.8 ± 0.8 dB higher than Albunex at first harmonic and 12.6 ± 0.8 dB higher at second harmonic. The ratio of the second harmonic to first harmonic RDA, which we called R₂/R₁, decreases at a rate of 7 dB/MHz for both agents with increasing frequency. The difference in the value of R₂/R₁ between FS069 and Albunex at any frequency was approximately 4.5 dB. R₂/R₁ was found to increase linearly as a function of the transmitted acoustic pressure for both agents. Simulations using the Rayleigh-Plesset equation show a decrease of R₂/R₁ at a rate of 5 dB/MHz. Comparison of experimental results with theory indicates that the shell elasticity parameter may be an increasing function of the mean diameter of the bubbles.     

Immunochemiluminometric assays (ICMA) specific for growth hormone releasing hormone 1-44 NH2 and 1-40 OH.

We describe specific two-site immunochemiluminometric assays able to directly measure human growth hormone-releasing hormone 1–44 NH₂ and 1–40 OH concentrations in unextracted plasma. A common N-terminal antibody was purified from polyclonal rabbit antisera to growth hormone-releasing hormone 1–44 NH₂ on a growth hormone-releasing hormone 1–29 NH₂ linked affinity column and labelled with chemiluminescent acridinium ester. C-terminal specific monoclonal antibodies to growth hormone-releasing hormone 1–44 NH₂ and 1–40 OH were raised in Balb/C mice and used as solid phase antibodies. Assay of fasting specimens from normal individuals gave medians (and ranges) of 23 pg/ml (2–200) and 30 pg/ml (3–134) for growth hormone-releasing hormone 1–44 NH₂ and 1–40 OH, respectively. Samples from a series of acromegalics showed that most have values in the normal range though median values were higher, 56 pg/ml for growth hormonereleasing hormone 1–44 NH₂ (P < 0.001) and 52 pg/ml for 1–40 OH (P < 0.001). Using these assays it will be possible for the first time to directly study the physiology and pathophysiology of these two peptides.     

Diagnosis of Tay-Sachs disease using [3H]N-acetylneuraminic acid labelled GM2 ganglioside as substrate

G_M2 ganglioside labelled with tritium in the N-acetylneuraminic acid moiety was prepared and used to measure β-hexosaminidase A activity in cultured human skin fibroblast extracts. The latter convert this substrate to the correspondingly labelled G_M3 ganglioside which can easily be separated from the substrate by thin-layer chromatography. No cleavage of the N-acetylneuraminic acid group was observed under our conditions.

Two methods are described for the determination of G_M2-β-hexosaminidase A activity in fibroblasts. The application of these methods to the diagnosis of Tay-Sachs disease is discussed.     

Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs

Gemcitabine is a known anticancer agent rapidly deaminated to the inactive metabolite 2′,2′-difluorodeoxyuridine; it must therefore be administered at very high dose. Many different approaches have been tried to improve the metabolic stability; we synthesized a series of increasingly lipophilic prodrugs of gemcitabine by linking the 4-amino group with valeroyl, heptanoyl, lauroyl and stearoyl linear acyl derivatives. We studied their stability at storage, in plasma and with the lysosomal intracellular enzyme cathepsins. We studied incorporation of these lipophilic prodrugs in liposomes, where their encapsulation efficiency (EE) closely depends on the length of the saturated 4-(N)-acyl chain, the phospholipids chosen and the presence of cholesterol. A maximum EE of 98% was determined for 4-(N)-stearoyl-gemcitabine incorporated in DSPC/DSPG 9:1. This formulation was correlated with the highest stability in vitro and in vivo. Cytotoxicity of gemcitabine prodrugs, free or encapsulated in liposomes, was between two- and sevenfold that of free gemcitabine. Encapsulation of long-chain lipophilic prodrugs of gemcitabine in liposomes protected the drug from degradation in plasma, assuring a long plasma half-time and intracellular release of the free drug.     

In vitro studies upon the release of γ-glutamyltransferase from human liver

Samples of human liver have been incubated in different fluids for up to 48 h and the released γ-glutamyltransferase studied by gel chromatography on Sephacryl S-300 and polyacrylamide gradient gel electrophoresis. When human liver is incubated in serum, most of the released enzyme is of high M_r (greater than 1 000 000). Incubation in hepatic bile, or in a solution of glycochenodeoxycholate, results in the release of enzyme that is hydrophobic in nature and which reaggregates to a varying extent after the removal of bile salts. In contrast, incubation in saline, or in a solution of human albumin results in the release of a hydrophilic low M_r (about 120 000) form of the enzyme. These observations are discussed in relation to possible mechanisms for the release of these multiple forms.     

A sensitive colorimetric assay for polyamines in erythrocytes using oat seedling polyamine oxidase

Background: Most of the polyamines circulating in blood are spermidine (Spd) and spermine (Spm) with only trace amounts of putrescine (Put), and they are mainly localized in erythrocytes. We developed a simple and sensitive colorimetric assay for polyamines in erythrocytes using oat seedling polyamine oxidase (OSPO). The method is based on the unique substrate specificity of OSPO, which is active toward Spd and Spm, but not toward diamines such as Put and cadaverine and monoamines such as histamine. Methods: The polyamines, which were purified from packed erythrocytes by weak cation-exchange chromatography, were incubated with OSPO at 37 °C for 15 min. In the presence of the H₂O₂ produced by this polyamine oxidase reaction and a new chromogen, N-(carboxymethylaminocarbonyl)-4,4′-bis(dimethylamino)-diphenylamine sodium salt (DA-64), peroxidase (POD) catalyzes the formation of N-[4-[[4-(dimethylamino)phenyl]imino]-2,5-cyclohexadien-1-ylidene]-N-methylmethanaminium chloride (Bindschedler's Green) having an absorption maximum at 727 nm. Results: The detection limit was 0.2 μmol/l for packed erythrocytes. The within-run and between-run precisions (coefficient of variation, CVs) were 5.6–15.2% and 6.5–16.4%, respectively. Analytical recoveries were 93.3–97.4%. Polyamine values obtained by this assay correlated well with those obtained by an HPLC (y=0.948x+1.912; r=0.944; n=46). Conclusions: This colorimetric assay is simple and highly sensitive and practical for clinical use.     

Treatment with N-acetylcysteine during acute respiratory distress syndrome: A randomized, double-blind, placebo-controlled clinical study

Intravenous N-acetylcysteine (NAC) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury. In the more serious form, namely established adult respiratory distress syndrome (ARDS) (Pao₂/Fio₂ ≤ 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial.

Respiratory dysfunction was graded daily according to the need for mechanical ventilation and Fio₂ and to the evolution of the lung injury score (LIS) and the Pao₂/Fi0₂ ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course.

NAC and placebo groups (22 and 20 patients, respectively) were comparable for demographic characteristics, ARDS categories, severity of illness (simplified acute physiology score [SAPS II]) LIS and Pao₂/Fio₂ ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (difference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at days 2, 3, 5, and 7 after admission, the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1. Moreover, there were no differences between the two groups at the same observation days. In both groups, the Fio₂ was significantly lower and the Pao₂/Fio₂ ratio was significantly higher than the initial values during the evolution (Fio₂ at day 3, P < .01 for NAC and P < .05 for placebo; Pao₂/Fio₂ at day 3: P < .01 for NAC and P < .02 for placebo), but this improvement was similar for both groups and, moreover, the between-group comparison was never significantly different at the various collection days. The LIS decreased significantly in NAC group between days 1 and 3 (2.23 ± 0.62 v 1.76 ± 0.17; P < .05), whereas no changes were observed in the placebo group; at day 5, there was a significant difference between the two groups (1.53 ± 0.21 for the NAC v 2.15 ± 0.19 for the placebo group; P < .05). In the prevalent sepsis category (10 patients in the NAC and 9 in the placebo group), the mortality rate, the need of ventilatory support, the intensive care unit stay, and the Pao₂/Fio₂ evolution did not differ significantly in both subgroups.

In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support oxygenation nor reduced the need for ventilatory support.     

临床化学实验室质量控制计算实际西格玛值的新方法

目的 计算实际西格玛(sigma,σ)值,正确评估实验室检测项目分析性能。方法 方法①结合室内质量控制(internal quality control,IQC),与室间质量评价(external quality assessment,EQA),计算westgard两种σ计算公式σ₁=(TEa-bias)/(s)和σ₂=(TEa%-bias%)/(CV%)下的σ₁与σ₂值。以IQC累积均值χ₁与EQA靶值μ₂的比值(χ₁/μ₂)为横轴,σ₁,σ₂为纵轴绘制散点图,比较σ₁,σ₂的关系; 方法②以伯乐公司全球质控材料,批号为45751和45753,仪器为罗氏Cobas 8000全自动生化分析仪,累积到2018年1月份的均值作为靶值μ₁,结合IQC数据计算Westgard两种公式下检测项目的σ₁,σ₂值。结果 方法①计算的σ₁与σ₂值并不相同,甚至相差很大,而且对钠(Na)、氯(Cl)、钙(Ca)三个TEa要求高的检测项目,σ值计算结果为负值。比较σ₁,σ₂的关系,当χ₁/μ₂<1时,σ₁>σ₂; 当χ₁/μ₂>1时,σ₁<σ₂。方法②中χ₁ /μ₁值接近于1,σ₁,σ₂大小非常接近。结论 结合IQC与EQA计算σ时,应选取与质控材料同一浓度水平的测定值,这才能真实反映实验室检测项目分析性能。     

High-flow nasal cannula oxygen therapy and noninvasive ventilation for preventing extubation failure during weaning from mechanical ventilation assessed by lung ultrasound score: A single-center randomized study

BACKGROUND: We sought to demonstrate the superiority of a targeted therapy strategy involving high-flow nasal cannula oxygen (HFNCO₂) therapy and noninvasive ventilation (NIV) using lung ultrasound score (LUS) in comparison with standard care among patients in the intensive care unit (ICU) who undergo successful weaning to decrease the incidence of extubation failure at both 48 hours and seven days. METHODS: During the study period, 98 patients were enrolled in the study, including 49 in the control group and 49 in the treatment group. Patients in the control group and patients with an LUS score <14 points (at low risk of extubation failure) in the treatment group were extubated and received standard preventive care without NIV or HFNCO₂. Patients with an LUS score ≥14 points (at high risk of extubation failure) in the treatment group were extubated with a second review of the therapeutic optimization to identify and address any persisting risk factors for postextubation respiratory distress; patients received HFNCO₂ therapy combined with sessions of preventive NIV (4-8 hours per day for 4-8 sessions total) for the first 48 hours after extubation. RESULTS: In the control group, 13 patients had the LUS scores ≥14 points, while 36 patients had scores <14 points. In the treatment group, 16 patients had the LUS scores ≥14 points, while 33 patients had scores <14 points. Among patients with the LUS score ≥14 points, the extubation failure rate within 48 hours was 30.8% in the control group and 12.5% in the treatment group, constituting a statistically significant difference (P<0.05). Conversely, among patients with an LUS score <14 points, 13.9% in the control group and 9.1% in the treatment group experienced extubation failure (P=0.61). The length of ICU stay (9.4±3.1 days vs. 7.2±2.4 days) was significantly different and the re-intubation rate (at 48 hours: 18.4% vs. 10.2%; seven days: 22.4% vs. 12.2%) significantly varied between the two groups (P<0.05). There was no significant difference in the 28-day mortality rate (6.1% vs. 8.2%) between the control and treatment groups. CONCLUSIONS: Among high-risk adults being weaned from mechanical ventilation and assessed by LUS, the NIV+HFNCO₂ protocol does not lessen the mortality rate but reduce the length of ICU stay, the rate of extubation failure at both 48 hours and seven days.     

Comparison of membrane filtration and nephelometry with analytical ultracentrifugation, for the quantitative analysis of low density lipoprotein fractions

The validity of membrane filtration and nephelometry for the separation and quantification of liquid-borne particle concentrations has been tested using polystyrene latex particles suspended in deionised water and using serial dilutions of serum in saline. The results demonstrate that this technique provides an accurate and reproducible means of analysis.

The results of analytical ultracentrifugal analysis have been compared with those of membrane filtration and nephelometry in 81 serum samples. A high correlation (r = 0.96) was demonstrated between S_f 20–400 lipoprotein concentrations and nephelometric measurements. The concentration of S_f 0–20 lipoproteins cannot be estimated by membrane filtration and nephelometry but could be predicted from nephelometric measurements and the estimation of serum total cholesterol (r = 0.83). Equations are given from which the concentrations of S_f 0–20 and S_f 20–400 lipoproteins can be calculated.