Acute palliative care unit-initiated interventions for advanced cancer patients at the end of life: prediction of impending death based on Glasgow Prognostic Score.

PURPOSE: Unexpected death occurred in an unexpectedly high proportion of advanced cancer patients in the acute palliative care unit (APCU) setting and associated with fewer signs of impending death. Recognition of patients at high risk of approaching death, especially immediately after admitting APCU among clinicians, can improve the end-of-life trajectory. Our objective was accurate prognostication within a few days of admission. METHODS: Patients admitted to an APCU of the NTT Medical Center Tokyo, Tokyo, Japan, between April 2009 and December 2016 were retrospectively examined. The Glasgow Prognostic Score (GPS) was optimized with concomitant neutrophilia, lymphocytopenia, thrombocytopenia, anemia, and monocytosis. Kaplan-Meier survival curves were estimated, and independent predictors for 3-day mortality were identified using univariate and multivariate analyses. The sensitivity, specificity, and likelihood ratios (LRs) associated with imminent death were also assessed. RESULTS: Nine hundred ninety-one patients were included; 52.9% was male. The median age was 72 years. The median survival was 13 days (IQ range 6 to 26), and 11.7% died within 3 days of admission. Significant difference in survival with a GPS of 2 was observed in GPS optimized with concomitant thrombocytopenia, and it was the only significant predictor associated with 3-day mortality (p = 0.004), which had high specificity (> 95%) and high positive LR (> 5). CONCLUSION: The prognostic value of the GPS was enhanced by adding thrombocytopenia. The concurrent use of the GPS and platelet count improved the prognostication of limited time of survival and could assist in the personal and clinical decisions for advanced cancer patients.

Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol.

OBJECTIVE: The onset and progression of non-alcoholic fatty liver disease (NAFLD) seem to be affected by nutritive intake; however, detailed examinations have not been performed in non-obese NAFLD patients. The purpose of this study was to identify potential nutritive factors that affect NAFLD and its related nutritional problems. MATERIAL AND METHODS: We investigated the distribution of abdominal fat, dietary intake, and biochemical data in patients with NAFLD and compared non-obese with obese patients. RESULTS: There was no significant difference in the percentage of patients with diabetes or dyslipidemia between the obese and non-obese groups. Waist circumference, total abdominal fat levels, and subcutaneous fat levels were significantly higher in the obese group, while visceral fat levels were not significantly different between the two groups. Immunoreactive insulin (IRI) and homeostasis model assessment-insulin resistance (HOMA-IR) were significantly lower in the non-obese group, suggesting that the non-obese patients were not overtly insulin resistant. Although serum adiponectin and TNF-alpha levels were similar in both groups, leptin levels were significantly higher in the obese group. Total energy and carbohydrate intake tended to be higher in the obese group. A characteristic feature was that dietary cholesterol intake was significantly higher, while the intake of polyunsaturated fatty acids (PUFAs) was significantly lower in the non-obese group. CONCLUSIONS: In non-obese NAFLD patients: 1) although visceral fat was increased, insulin resistance and/or dysregulated secretion of adipocytokines was not necessarily shown; 2) intakes of total energy and carbohydrates were not excessive, although dietary cholesterol was superabundant and dietary PUFAs were significantly lower compared with those in obese patients; and 3) characteristic fat intake may be associated with the formation of NAFLD.

Structural change of water with solutes and temperature up to 100 degrees C in aqueous solutions as revealed by attenuated total reflectance infrared spectroscopy.

The attenuated total reflectance infrared (ATR-IR) spectra of several aqueous solutions have been measured by using a newly developed heatable rod-type ATR cell. The OH stretching bands showed systematic change with increasing solute concentrations and these changes can be explained by four different OH components based on curve-fitting results. NaCl solutions show longer H-bond distance character, while carbonate solutions present shorter ones. The Na2CO3 1 M solution conserves this shorter H-bond nature up to 100 degrees C. On the other hand, the loose nature of NaCl solutions becomes less pronounced at higher temperatures because of the dissociation of pure water clusters. These in situ observations of water structures are generally in agreement with the expected nature of fluids within the earth.

Accelerated clearance of a second injection of PEGylated liposomes in mice.

We recently reported that the firstly injected PEGylated liposomes dramatically affected the rate of blood clearance of secondly injected PEGylated liposomes in rats in a time interval of injection dependent manner [J. Control. Release (2003)]. Mice are frequently used in evaluations of the therapeutic efficacy of PEGylated liposomal formulations, but the pharmacokinetics of repeatedly injected PEGylated liposomes in mice is not fully understood. In this study, therefore, we examined in mice the effect of the repeated injection of PEGylated liposomes on their pharmacokinetics. An intravenous pretreatment with PEGylated liposomes produced a striking change in the biodistribution of the second dose which was given several days after the first injection. The first dose resulted in a reduction in the circulation half-life of the second dose. The degree of alteration was dependent on the time interval between the injections. The rapid clearance of the second dose was strongly related to hepatic clearance (CLh). This finding suggests that a considerable increase in hepatic accumulation accounts for this phenomenon. But, no liver injury or an increase in the number of Kupffer cells were detected in histopathological evaluations. Collectively, although the multiple injections of the PEGylated liposomes had no obvious physical effects, such as inflammation, their pharmacokinetic behavior was clearly altered in mice. The results obtained here have important implications not only with respect to the design and engineering of liposomes for human use, but for evaluating the therapeutic efficacy of liposomal formulations in experimental animal models as well.

Oral antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates from Japanese children.

The minimum inhibitory concentrations (MICs) of 11 oral antibiotics were measured for 140 Streptococcus pneumoniae, 115 Haemophilus influenzae, and 46 Moraxella catarrhalis strains isolated from Japanese children. The antibiotics selected included a range of commonly prescribed agents together with a selection of new cefems and a penem. Cefditoren was most active against the highly penicillin resistant S. pneumoniae, beta-lactamase-producing H. influenzae and beta-lactamase-negative ampicillin-resistant H. influenzae. However, amoxycillin retained good activity against the penicillin-susceptible or -intermediately resistant S. pneumoniae (88.6%) and most of ampicillin-susceptible or -intermediately resistant H. influenzae (87.9%). We thus consider that amoxycillin remains a useful initial choice for the treatment of paediatric respiratory infections in Japan.

Incidences of nasopharyngeal colonization of respiratory bacterial pathogens in Japanese children attending day-care centers.

BACKGROUND: In Japan, many younger children attending day-care centers tend to frequently experience acute respiratory infections and prolonged otitis media. OBJECTIVES: To evaluate the carriage rate of respiratory bacterial pathogens in children attending day-care centers in our district. METHODS: Nasopharyngeal cultures of 156 healthy children between the ages of 1 month and 5 years were conducted at two day-care centers in Japan, in April 1999. The carriage rates of four major pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus) and the antibiotic susceptibilities of the isolates were examined. RESULTS: Streptococcus pneumoniae, H. influenzae, M. catarrhalis and S. aureus were detected in 94 (60.3%), 83 (53.2%), 54 (34.6%) and 28 (17.9%) children, respectively. A total of 141 (90.4%) children carried at least one pathogen among these four pathogens and 87 (55.8%) children carried more than one pathogen. Fifty-seven of the 94 (60.6%) S. pneumoniae isolates were penicillin-intermediately or highly resistant strains of S. pneumoniae (PISP/PRSP). Beta-lactamase producing H. influenzae was not detected. Twelve of the 28 (42.9%) S. aureus isolates were methicillin-resistant. The incidence of colonization by PISP/PRSP in children younger than 3 years (43/69, 62.3%) was significantly higher than that in children aged 3-5 years (14/87, 16.1%) (P < 0.0001). CONCLUSIONS: We conclude that the rates of colonization by respiratory bacterial pathogens, especially by antibiotic-resistant strains, were high in children attending day-care centers in our district, suggesting their horizontal spread among children in day-care centers. Considering that the majority of children attending day- care centers carried one or more of the bacterial pathogens, the judicious use of antimicrobials will be required to prevent the increase of antibiotic-resistant rates among the colonizing pathogens.

Some Properties of the Hardening Process in Chorions Isolated from Unfertilized Eggs of Medaka, Oryzias latipes: (Fish Egg Envelope/Chorion/Chorion Proteins/Chorion Hardening/In Vitro Ca2+ -Hardening).

Chorions isolated from unfertilized eggs of medaka, Oryzias latipes, harden during incubation with Ca2+ ions (Masuda et al., 1991). In this process, i.e. in vitro Ca2+ -hardening, the amounts of the major proteins of unfertilized egg chorions (83 K, 78 K and 51 K, corresponding to ZI-1, 2 and 3 of oocyte chorions reported by Hamazaki et al, 1987) decreased and new proteins having molecular weights of 148 K or more appeared. Immunoblotting analysis using anti-ZI-1, 2 antisera and anti-ZI-3 antisera showed that the 148 K protein was an intermediate formed during polymerization of the original proteins. The mechanism of in vitro Ca2+ -hardening was studied by examining the decrease in ZI-1, 2, and 3, the formation of 148 K protein, and the change in solubility of chorions in 6% sodium dodecylsulfate-1% 2-mercaptoethanol-15% glycerol-0.2 M Tris-HCl (pH 6.8). In vitro Ca2+ -hardening was inhibited at temperatures higher than 70°C and its optimum pH was about 5.5. It was inhibited by neither aminotriazole nor cadaverine. The results suggested that in vitro Ca2+ -hardening was generated by some factor(s) other than ovoperoxidase and transglutaminase.

Analysis of Hardening of the Egg Envelope (Chorion) of the Fish, Oryzias latipes: (Egg envelope (chorion)/Egg activation/Chorion hardening/Fish egg/Chorion proteins).

Hardening of the chorion of medaka eggs was quantitated in terms of the solubility of its constituent proteins. After activation of unfertilized eggs with the Ca2+ -ionophore A23187, hardening of chorion (named ionophore-activation hardening) proceeded and 60 min after activation the solubility of the proteins in 1 N NaOH had decreased to 20% of that of proteins of unhardened chorions. On SDS-PAGE, the chorions of unfertilized eggs gave four major protein bands (150, 83, 78 and 51 K). After Ca2+ -ionophore activation, new two protein bands (135 and 61 K) appeared, with concurrent disappearance of all the original bands except the 51 K band. Isolated chorions of unfertilized eggs were also hardened by Ca2+ and 60 min after addition of Ca2+ the solubility of their proteins in 1 N NaOH had decreased to about 45% of that originally. During this type of hardening (named 'Ca2+ -hardening), however, the SDS-PAGE pattern of the proteins remained unchanged. Therefore, there are two mechanisms of hardening. The 'ionophore-activation hardening was inhibited by cadaverine. When chorions were isolated 20 min after Ca2+ -ionophore activation and kept in Ca2+ -free conditions, the 'ionophore-activation hardening process was arrested: further hardening was resumed on addition of Ca2+ to the medium. These results suggest the presence of some hardening machinery in isolated chorions.

Change in Component Proteins of the Egg Envelope (Chorion) of Rainbow Trout during Hardening: (Fish Egg Envelope/Chorion/Chorion Proteins/Chorion Hardening/Egg Activation).

Egg envelope (chorion) of unfertilized eggs of rainbow trout, Oncorhynchus mykiss, consists of 4 major protein components whose molecular weights are approximately 110 K, 64 K, 56 K and 50 K. On hardening of the chorion after activation, 64 K, 56 K and 50 K components disappeared, some components higher than 160 K were newly formed and the solubility of the chorion in 1 N NaOH or 12 M urea-2% SDS-1% 2-mercaptoethanol (Sample Buffer) decreased. This implies that probable formation of covalent crosslinks between the constituents occurs during the hardening. Hardening occurred also in the chorion isolated from the unfertilized eggs. The conversion of the 64 K, 56 K and 50 K components into the higher molecular weight intermediates was Ca2+ -dependent, accelerated by 2-mercaptoethanol and inhibited by a high temperature (60°C). Optimum pH of this hardening system was acidic, i.e., 5.0 to 6.0. Cadaverine inhibited the change in solubility of chorion in NaOH or Sample Buffer, while it could not inhibit the disappearance of the 64 K, 56 K and 50 K components and the new formation of the higher molecular weight intermediates. This observation indicates existence of two processes in chorion hardening, which are tentatively named cadaverine-insensitive and cadaverine-sensitive processes.