A Consideration on the new classification of latest lung ventilators

Concerning the classification of ventilators, Elam (1958), Faireley (1959), and Hunter (1961) reported some simple ones such as pressure limited, volume limited, pressure preset, or volume preset models. Mapleson (1969) also classified them by the generating force or cycling together with the above-mentioned types.The latest ventilators applicable to patients with respiratory failure usually have some cut-off function at high airway pressures as a safety measure. Therefore, all of them belong to the pressure limited type. Some ventilators are of two types such as the time cycled and pressure cycled type.Therefore, we attempted to classify ventilators into four groups, i.e. the time cycled, volume cycled, pressure cycled and selective time-pressure cycled types according to the fundamental mode of ventilator function, the so-called change of cycling from inspiration to expiration. Each group was further divided into subgroups according to preset dials such as respiratory rate, I/E ratio, inspiration time, expiration time, tidal volume, flow rate and airway pressure.By this method, fifty one ventilators on the market in Japan can be classified without overlapping. Although this classification seems complex, it will be of use in selecting ventilators by emphasizing preset dials according to the users needs, ability or both.(Goto Y, Takahashi K, Harada J et al.: A consideration on the new classification of latest lung ventilators. J Anesth 1: 178–182, 1987)     

Association between Vitamin D and Heart Failure Mortality in 10,974 Hospitalized Individuals

A broad range of chronic conditions, including heart failure (HF), have been associated with vitamin D deficiency. Existing clinical trials involving vitamin D supplementation in chronic HF patients have been inconclusive. We sought to evaluate the outcomes of patients with vitamin D supplementation, compared with a matched cohort using real-world big data of HF hospitalization. This study was based on the Diagnosis Procedure Combination database in the Japanese Registry of All Cardiac and Vascular Datasets (JROAD-DPC). After exclusion criteria, we identified 93,692 patients who were first hospitalized with HF between April 2012 and March 2017 (mean age was 79 ± 12 years, and 52.2% were male). Propensity score (PS) was estimated with logistic regression model, with vitamin D supplementation as the dependent variable and clinically relevant covariates. On PS-matched analysis with 10,974 patients, patients with vitamin D supplementation had lower total in-hospital mortality (6.5 vs. 9.4%, odds ratio: 0.67, p < 0.001) and in-hospital mortality within 7 days and 30 days (0.9 vs. 2.5%, OR, 0.34, and 3.8 vs. 6.5%, OR: 0.56, both p < 0.001). In the sub-group analysis, mortalities in patients with age < 75, diabetes, dyslipidemia, atrial arrhythmia, cancer, renin-angiotensin system blocker, and β-blocker were not affected by vitamin D supplementation. Patients with vitamin D supplementation had a lower in-hospital mortality for HF than patients without vitamin D supplementation in the propensity matched cohort. The identification of specific clinical characteristics in patients benefitting from vitamin D may be useful for determining targets of future randomized control trials.     

Effects of MEK on kinetics ofn-hexane metabolites in serum

The neurotoxicity ofn-hexane is thought to be caused ultimately by 2,5-hexanedione (2,5-HD), one of then-hexane metabolites. The potentiation ofn-hexane neurotoxicity by co-exposure with MEK, therefore, is suspected to be related to kinetics of 2,5-HD in blood. To clarify the kinetics ofn-hexane metabolites in the mixed exposure ofn-hexane and MEK, rats were exposed to 2000 ppmn-hexane or a mixture of 2000 ppmn-hexane and 2000 ppm MEK, and the time courses of serumn-hexane metabolites were determined. 2,5-HD in serum increased until 2 h after the end of exposure, when serum 2,5-HD concentration reached a peak of 16.35 g/ml in then-hexane-alone group. In contrast, 2,5-HD in the mixed exposure group increased much more slowly during and after exposure than in then-hexane-alone group. It reached a peak of 2.12 g/ml at 8 h after the end of exposure. Serum MBK, a precursor of 2,5-HD in the co-exposure group, was about half in then-hexane-alone group during exposure. However, MBK decreased more slowly in the co-exposure group than in then-hexane-alone group after the end of the exposure. The results suggest that co-exposed MEK might inhibit oxidation ofn-hexane and decrease clearance ofn-hexane metabolites. Co-exposed MEK did not increase serum 2,5-HD, which was considered a main neurotoxic metabolite. Therefore the enhancement of neurotoxicity could not be attributed to increased serum 2,5-HD in the co-exposed group. The mechanism of enhancement of neurotoxicity ofn-hexane by MEK should be studied further.     

A randomized trial of 72- versus 24-hour intravenous tubing set changes in newborns receiving lipid therapy.

OBJECTIVE: To compare the microbial contamination rate of infusate in the intravenous tubing of newborns receiving lipid therapy, replacing the intravenous delivery system at 72-hour versus 24-hour intervals. DESIGN: Infants requiring intravenous lipid therapy were randomly assigned to have intravenous sets changed on a 72- or a 24-hour schedule, in a 3:1 ratio, in order to compare the infusate contamination rates in an equivalent number of tubing sets. SETTING: A 35-bed, teaching, referral, neonatal intensive-care unit (NICU). PARTICIPANTS: All neonates admitted to the NICU for whom intravenous lipid was ordered. METHODS: Patients were randomized in pharmacy, on receipt of the order for intravenous lipid therapy, to either 72- or 24-hour administration set changes, and followed until 1 week after discontinuation of lipids or discharge from the NICU. Microbial contamination of the infusate was assessed in both groups at the time of administration set changes. Contamination rates were analyzed separately for the lipid and amino acid-glucose tubing sets. Patient charts were reviewed for clinical and epidemiological data, including birth weight, gestational age, gender, age at start of lipid therapy, duration of parenteral nutrition, and type of intravenous access. RESULTS: During the study period, 1,101 and 1,112 sets were sampled in the 72- and 24-hour groups, respectively. Microbial contamination rates were higher in the 72-hour group than the 24-hour group for lipid infusions (39/1,101 [3.54%] vs 15/1,112 [1.35%]; P=.001) and for amino acid infusions (12/1,093 [1.10%] vs 4/1,103 [0.36%]; P=.076). Logistic regression analysis controlling for birth weight, gestational age, and type of venous access showed that only the tubing change interval was significantly associated with lipid set contaminations (odds ratio, 2.69; P=.0013). The rate of blood cultures ordered was higher in the 72- versus the 24-hour group (6.11 vs 4.99 per 100 patient days of total parenteral nutrition; P=.017), and a higher proportion of infants randomized to the 72-hour group died (8% vs 4%; P=.05), although the excess deaths could not clearly be attributed to bacteremia. CONCLUSION: Microbial contamination of infusion sets is significantly more frequent with 72- than with 24-hour set changes in neonates receiving lipid solutions. This may be associated with an increased mortality rate.     

Pharmacokinetics and Biodistribution of Oligonucleotide Adsorbed onto Poly(isobutylcyanoacrylate) Nanoparticles After Intravenous Administration in Mice

Purpose. The goal of this study was to evaluate the ability of nanoparticles to be used as a targeted delivery system for oligonucleotides. Methods. Pharmacokinetic and tissue distribution were carried out in mice by measuring the radioactivity associated to the model oligothymidylate ³³P-pdT₁₆ loaded to poly(isobutylcyanoacryrate) (PIBCA) nanoparticles. In addition, we have used a TLC linear analyzer to measure quantitatively on a polyacrylamide gel electrophoresis, the amount of non degraded pdT₁₆ Results. Organ distribution study has shown that nanoparticles deliver ³³P-pdT₁₆ specifically to the liver reducing its distribution in the kidney and in the bone marrow. Nanoparticles could partially protect pdT₁₆ against degradation in the plasma and in the liver 5 min after administration, whereas free oligonucleotide was totally degraded at the same time. Conclusions. Nanoparticles protect oligonucleotides in vivo against degradation and deliver them to the liver.     

Reduced MLH1 expression after chemotherapy is an indicator for poor prognosis in esophageal cancers.

PURPOSE: Loss of function or expression of the mismatch repair gene MLH1 has been implicated in experimentally acquired resistance to cisplatin (CDDP) and other anticancer agents. The clinical significance of MLH1 expression was evaluated in advanced thoracic squamous cell carcinoma of the esophagus (ESCC) treated by neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: We investigated MLH1 and P53 expression by immunohistochemistry in the surgical specimens of 107 patients who had undergone preoperative chemotherapy using CDDP along with 5-FU and ADM. These findings were correlated with the clinical outcome for this treatment. Biopsy samples before chemotherapy in 20 of these patients, and another 43 surgical specimens without chemotherapy, were also examined as control samples. RESULTS: In surgical specimens of ESCC, low MLH1 expression was not frequent without chemotherapy, whereas it was commonly observed after chemotherapy (14 versus 37%, P = 0.0057). Comparison between samples before and after chemotherapy revealed that MLH1 expression was unchanged during chemotherapy in 12 of 20 patients (60%) but was from high to low in 8 of 20 patients (40%). In the surgical specimen after neoadjuvant chemotherapy, MLH1 expression was not correlated with any clinicopathological factors, including the response to chemotherapy. However, low MLH1 showed poorer prognosis than high MLH1 (5-year survival 40.6 versus 19.3%, P = 0.0393), and in multivariate analysis, MLH1 was an independent prognostic factor for this multimodal treatment, following lymph node metastasis and clinical response to chemotherapy. Positive p53 expression, which was not affected by chemotherapy, was weakly associated with a poor response and clinical outcome, although this trend was not significant. CONCLUSIONS: In advanced ESCC, expression of MLH1 is reduced during CDDP-based chemotherapy, and this may partly account for poor postoperative survival.     

Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma

PURPOSE: To investigate whether nitric oxide excreted from cells irradiated with accelerated carbon-ion beams modulates cellular radiosensitivity against irradiation in human glioblastoma A-172 and T98G cells. MATERIALS AND METHODS: Western-blot analysis of inducible nitric oxide synthase, hsp72 and p53, the concentration assay of nitrite in medium and cell survival assay after irradiation with accelerated carbon-ion beams were performed. RESULTS: The accumulation of inducible nitric oxide synthase was caused by accelerated carbon-ion beam irradiation of T98G cells but not of A-172 cells. The accumulation of hsp72 and p53 was observed in A-172 cells after exposure to the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams, and the accumulation was abolished by the addition of an inhibitor for inducible nitric oxide synthase to the medium. The radiosensitivity of A-172 cells was reduced in the conditioned medium of the T98G cells irradiated with accelerated carbon-ion beams compared with conventional fresh growth medium, and the reduction of radiosensitivity was abolished by the addition of an inducible nitric oxide synthase inhibitor to the conditioned medium. CONCLUSIONS: Nitric oxide excreted from the irradiated donor cells with accelerated carbon-ion beams could modulate the radiosensitivity of recipient cells. These findings indicate the importance of an intercellular signal transduction pathway initiated by nitric oxide in the cellular response to accelerated heavy ions.     

A Comparison of Visual Field and Optic Disc Appearance Depending on the Peak Intraocular Pressure in Patients with Normal-tension Glaucoma

Purpose To review the outcome of surgery for strabismus due to ethmoid sinus surgery.Cases and Methods The series comprised 13 cases, 1 of inferior rectus paresis, 1 of superior oblique paresis, 6 of medial rectus paresis, and 5 of medial rectus muscle palsy due to third nerve palsy. In the cases of paresis of the rectus muscle, resection of the rectus muscles was mainly performed. In the cases of palsy of the rectus muscle, transposition of the extraocular muscle with simultaneous recession of the lateral rectus muscle was performed. The major aim of surgery was to bring both eyes into alignment and to eliminate diplopia in the primary position.Results The mean preoperative horizontal deviation of 18.1 degrees of exotropia in the paresis cases was reduced to 1.4 degrees of exotropia after surgery. The mean preoperative vertical deviation of 3.8 degrees of hypertropia was reduced to 1.4 degrees of hypertropia postoperatively. The mean preoperative horizontal deviation of 35.6 degrees of exotropia in the palsy cases was reduced to 9.4 degrees of exotropia after surgery. The mean preoperative vertical deviation of 2.0 degrees of hypertropia was increased to 2.6 degrees of hypertropia postoperatively. Postoperatively, diplopia was absent in 11 cases with a slightly compensatory head posture.Conclusions Surgery for strabismus due to sinus surgery induces improvements in eye position and diplopia. Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc 107:425–432, 2003)     

Histological findings after angioplasty using conventional balloon, radiofrequency thermal balloon, and stent for experimental aortic coarctation

Abstract Background : Use of balloon angioplasty or stent implantation has been reported to be effective in relieving coarctation of the aorta. However, restenosis frequently occurs after balloon angioplasty for native aortic coarctation in small infants, and sometimes develops after stent implantation because of vessel growth. The causes of restenosis remain uncertain. The purpose of this study was to assess the histologic differences in vascular responses to angioplasty using conventional balloon, radiofrequency thermal balloon (RFTB), or stent for experimental aortic coarctation. Methods : The authors surgically created an aortic coarctation model using 14 puppies. Angioplasty using conventional balloon, RFTB, or stent was performed 1 month after the initial operation. At the acute or chronic phase after angioplasty, the animals were killed and histologic studies were performed. Results : More vascular injuries were noted in the specimens from animals undergoing conventional angioplasty than in those with RFTB or stent. However, neointimal hyperplasia was seen more often after RFTB or stent because of the proliferation of smooth muscle cells from the tunica media, caused by secretion of growth factors. Apoptosis reached a peak 1?2 weeks after angioplasty, regardless of the type of intervention. Conclusions : The authors conclude that angioplasty with RFTB or stent can provide relatively small injuries in the vessel wall for aortic coarctation, but care must be taken to prevent restenosis caused by intimal hyperplasia, because neointima hyperplasia is more frequent after RFTB or stent.