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Objective and Methods An SGLT2 inhibitor (ipragliflozin, dapagliflozin, luseogliflozin, tofogliflozin, or canagliflozin) was administered to 132 outpatients with type 2 diabetes mellitus with or without other antidiabetic drugs for 6 months to evaluate its efficacy, the incidence of adverse events, and its influence on the renal function. Results The patient's mean glycated hemoglobin level significantly improved from 7.52±1.16% to 6.95±0.98% (p

To investigate whether steroid replacement therapy improved hemodynamics in infants after surgery for congenital heart disease only when they develop adrenal insufficiency. The authors retrospectively investigated adrenal function and evaluated hemodynamic responses to steroid replacement therapy in infants after surgery for congenital heart disease.Retrospective, cohort study.Intensive care unit in the National Cerebral and Cardiovascular Center Hospital in Japan.Thirty-two neonates and infants3 months old who underwent cardiovascular surgery.The patients were divided into 2 groups based on corticotropin stimulation test results: group AI with adrenal insufficiency (baseline cortisol15 µg/dL or incremental increase after testing of9 µg/dL, with baseline cortisol of 15-34 µg/dL); and group N with normal adrenal function. The corticotropin stimulation test was performed by injecting 3.5 µg/kg of tetracosactide acetate. Hydrocortisone (1 mg/kg) was administered every 6 hours, and hemodynamics were compared before and after steroid administration between the groups.Seven patients were classified into group AI, and demonstrated a mean blood pressure increase from 53±8 mmHg before treatment to 68±9 mmHg 18 hours after steroid administration (p0.01). Urine output also increased, from 2.7±1.0 mL/kg/h to 4.8±1.9 mL/kg/h (p0.05). In group N, neither mean blood pressure nor urine output increased after steroid administration.After surgery for congenital heart disease, one-fifth of infants developed adrenal insufficiency. Steroid replacement therapy improved hemodynamics only in the subgroup with adrenal insufficiency.

To determine the specific effect of peak volume history pressure on the inflation limb of the pressure-volume curve and peak pressure-volume curve pressure on the deflation limb of the pressure-volume curve.Prospective assessment of pressure-volume curves in saline, lung lavage injured sheep.Large animal laboratory of a university-affiliated hospital.Eight female Dorset sheep.: The effect of two volume history pressures (40 and 60 cm H2O) and three pressure-volume curve peak pressures (40, 50, and 60 cm H2O) were randomly compared.Peak volume history pressure affected the inflation curve beyond the lower inflection point but did not affect the inflection point (Pflex). Peak pressure-volume curve pressure affected the deflation curve. Increased peak volume history pressure increased inflation compliance (p.05). Increased peak pressure-volume curve pressure increased the point of maximum compliance change on the deflation limb and deflation compliance and decreased compliance between peak pressure and the point of maximum curvature on the deflation limb (p.05).Peak volume history pressure must be considered when interpreting the inflation limb of the pressure-volume curve of the respiratory system beyond the inflection point. The peak pressure achieved during the pressure-volume curve is important during interpretation of deflation compliance and the point of maximum compliance change on the deflation limb.

Objective: To ascertain whether the locations of ventilator-induced lung injury (VILI) are influenced by body position. Design: Randomized prospective short-term study. Setting: Animal laboratory at a university school of medicine. Interventions: Twelve white rabbits were mechanically ventilated in IMV mode with an infant ventilator (V.I.P. Bird, Bird Products, Palm Springs, Calif., USA). Based on the results of a preliminary study to determine the ventilator settings at which the lungs of rabbits were injured within 5 h in the supine position, the ventilator was set at FIO2 0.21, at a rate of 30/min, TI 0.6 s, peak inspiratory pressure 30 cm H2O, inspiratory flow 10 l/min with no applied positive end-expiratory pressure (PEEP). Six of the animals were tested in the supine position and the other six in the prone position. Respiratory gases were measured and CT scanning was performed every 30 min. The animals were ventilated for 5 h or until pulmonary parenchymal opacification was detected. The lungs were divided into three areas from apex to base and three levels from ventral to dorsal, and the location of opacification was ascribed according to this scheme. After the experiment, the lungs were excised and examined histologically. Measurements and results: Parenchymal opacification occurred mainly in the dorsal lung areas. The time from the beginning of ventilation to the appearance of lung damage was 60–120 min in the supine (S) group, and 60–270 min in the prone (P) group, and it was significantly longer in the prone group (P

RATIONALE AND OBJECTIVES To investigate whether expiratory high-resolution computed tomography (HRCT) is more useful than inspiratory HRCT for the detection of early-phase diffuse alveolar damage. METHODS Eleven anesthetized rabbits were scanned with both inspiratory and expiratory HRCT every 30 minutes during mechanical ventilation. Ten rabbits were killed after the detection of pulmonary abnormalities on both inspiratory and expiratory HRCT. The remaining rabbit was killed when the pulmonary abnormalities appeared only on expiratory HRCT. RESULTS In four cases (36%), the abnormal findings were detected earlier on expiratory HRCT than on inspiratory HRCT. In seven cases (64%), the abnormalities appeared simultaneously on inspiratory and expiratory HRCT. In all 11 cases, the histopathological changes of areas with abnormal CT findings corresponded to the exudative or proliferative phase of diffuse alveolar damage. CONCLUSIONS Expiratory HRCT has the potential to detect the abnormalities of diffuse alveolar damage earlier than inspiratory HRCT.

3.5～5.0mmの気管内チューブを使用した2ヵ月～14歳の小児1,113例を対象とし,実際に使用した気管内チューブのサイズを,年齢によるチューブサイズの予測式:チューブ内径(mm)=年齢×1/4+4.0,および身長によるチューブサイズの予測式:チューブ内径=身長×1/30+1.0(1歳未満),チューブ内径=身長×1/20(1歳以上)と比較した.さらに予測したサイズより1mm以上逸脱した症例についてその原因を検討した.今回使用した予測式では,身長からの計算では適正(実際に使用されたサイズ)よりもやや細めのチューブが,年齢からの計算ではやや太めのチューブが選択される傾向にあった.適正サイズが身長からの予測より1mm以上細かったものは2例で,小顎症,口蓋裂の既往がみられた.年齢からの予測式より1mm以上細かったものは6例で,低身長,低体重などが多かった.両予測式よりの1mm以上の逸脱症例は,食道閉鎖術後で低身長,低体重の1例であった.適正サイズが予測値より1.0mm以上太かった症例が2例あったが.その原因となるべき背景因子は認められなかった.

The distribution of liposomes with different membrane fluidity and vesicle size in tumors after intravenous injection was investigated in Yoshida sarcoma-bearing rats. Liposomes composed of egg phosphatidylcholine (EPC) or hydrogenated egg phosphatidylcholine (HEPC), dicetyl phosphate and cholesterol in a molar ratio of 5:1:4 were prepared. Their size was adjusted so that they had various mean diameters, ranging from 40 to 400 nm. In EPC liposomes, whose membranes were more fluid than those of HEPC liposomes, tumor accumulation increased with increasing area under the blood concentration-time curve (AUC). The size of liposomes which showed the greatest tumor accumulation and AUC was around 100 nm in diameter. In HEPC liposomes, the less fluid type, the size dependence of tumor accumulation and AUC differed. The greatest tumor accumulation or AUC were found in liposomes with a diameter of about 100 or 40 nm, respectively. This discrepancy indicates that the tumor accumulation of liposomes is not always correlated with their circulation time in the blood. To clarify the process by which these liposomes accumulate from the vascular space into the tumor, we calculated tumor uptake clearance (CL tu ), which can separate the contribution of the blood concentration from the accumulation in tumor. The CL tu values for EPC and HEPC liposomes agreed at all sizes, liposomes with a diameter of 100 nm showing the highest values. These findings indicate that the accumulation of liposomes from the vascular space into the tumor is primarily governed by their size and not by their membrane fluidity or blood circulation time. When tumor blood flow was selectively enhanced by the infusion of angiotensin II, the CL tu of 100-nm liposomes decreased to the level of that in 40-nm liposomes, suggesting that some histological factor(s) in the tumor may be responsible for the localization of 100-nm liposomes in tumor. In an in vitro experiment using cultured Yoshida sarcoma cells, 59-nm HEPC liposomes were directly taken up by the tumor cells to an extent at least 2.5-times greater than larger liposomes (> 100 nm). We conclude that 100-nm liposomes may predominantly localize in the interstitial space, whereas some liposomes of smaller size may be taken up by tumor cells.

Delivering warm, humidified gas to patients is important during mechanical ventilation. Heated humidifiers are effective and popular. The humidifying efficiency is influenced not only by performance and settings of the devices but the settings of ventilator. We compared the efficiency of humidifying devices with a heated wire and servo-controlled function under a variety of ventilator settings. A bench study was done with a TTL model lung. The study took place in the laboratory of the University Hospital, Osaka, Japan. Four devices (MR290 with MR730, MR310 with MR730; both FisherPaykel, ConchaTherm IV; Hudson RCI, and HummaxII; METRAN) were tested. Hummax II has been developed recently, and it consists of a heated wire and polyethylene microporous hollow fiber. Both wire and fiber were put inside of an inspiratory circuit, and water vapor is delivered throughout the circuit. The Servo 300 was connected to the TTL with a standard ventilator circuit. The ventilator settings were as follows; minute ventilation (V(E)) 5, 10, and 15 L/min, a respiratory rate of 10 breaths/min, I:E ratio 1:1, 1:2, and 1:4, and no applied PEEP. Humidifying devices were set to maintain the temperature of airway opening at 32 degrees C and 37 degrees C. The greater V(E) the lower the humidity with all devices except Hummax II. Hummax II delivered 100% relative humidity at all ventilator and humidifier settings. When airway temperature control of the devices was set at 32 degrees C, the ConchaTherm IV did not deliver 30 mg/L of vapor, which is the value recommended by American National Standards at all V(E) settings. At 10 and 15 L/min of V(E) settings MR310 with MR730 did not deliver recommended vapor, either. In conclusion, airway temperature setting of the humidifying devices influenced the humidity of inspiratory gas greatly. Ventilatory settings also influenced the humidity of inspiratory gas. The Hummax II delivered sufficient water vapor under a variety of minute ventilation.

Dexmedetomidine is a highly selective alpha(2)-adrenergic agonist that can reduce anesthetic requirements. This study, to assess its effect on respiration, examined the effects of various doses of dexmedetomidine (1, 10, 30 and 50 microg/kg) on the respiratory response to carbon dioxide (CO(2)) breathing in rabbits.Randomized prospective study.Animal laboratory at a university school of medicine.From 28 animals, four groups of seven were randomly assigned to receive different doses of dexmedetomidine (groups D1, D10, D30 and D50). Under inhalation of sevoflurane, each animal was tracheostomized and intubated with a 4 mm internal diameter (i.d.) endotracheal tube.After end-tidal sevoflurane concentration had decreased below 0.03% and during quiet breathing (QB); respiratory rate (RR), tidal volume (V(T)) and inspiratory time (T(I)) were measured, from which minute ventilation (MV) and mean inspiratory flow (V(T)/T(I)) were calculated. After these measurements had been completed, each animal breathed the balloon gas (5% CO(2) and 95% O(2)) until the end-tidal CO(2) (ETCO(2)) reached 10%. The respiratory measurements were repeated during the latter period. After the collection of these data, dexmedetomidine was infused intravenously and the same measurements were repeated 15 and 45 min after dexmedetomidine infusion. The slope of the ventilatory response to hypercapnia in D50 was significantly higher compared with D30 animals. In the range 1-30 microg/kg, during both QB and at 10% ETCO(2), MV was decreased in a dose-dependent manner. Dexmedetomidine depressed both V(T) and RR during QB and at 10% ETCO(2).Dexmedetomidine depressed resting ventilation and the respiratory response to CO(2), but it did not induce profound hypoxemia or hypercapnia in rabbits.

The objective of this study is to clarify to what extent the accumulation of liposomes from the blood into the tumor and bone marrow can be controlled by liposome size and membrane fluidity. Liposomes with different diameters (50–400 nm) and different membrane fluidity were prepared from hydrogenated egg phosphatidylcholine (HEPC) or egg phosphatidylcholine (EPC), cholesterol (Ch) and dicetylphosphate in various molar ratios. These liposomes were injected intravenously into rats bearing Yoshida sarcoma, and the ratios of the accumulation of liposomes in the tumor to those in the bone marrow, liver and spleen were compared. The tumor-to-bone marrow accumulation ratio increased with the decrease in liposome size from 400 to 50 nm. This ratio was greater than those for the liver and spleen at all sizes. Although tumor-to-liver accumulation ratios of 50- and 100-nm HEPC-containing liposomes were higher than those of EPC-containing liposomes, no obvious difference in tumor-to-bone marrow or tumor-to-spleen accumulation ratios was found between these liposomes. Tumor-to-bone marrow accumulation ratio of HEPC-containing liposomes increased remarkably with the decrease in Ch content from 40 to 30 or 20 mol% compared with ratios for the liver and spleen. Interestingly, the tumor uptake clearance of liposomes of the same size was constant regardless of their membrane fluidity. These findings show that the increases in these accumulation ratios are due to their decreased uptake clearance by the bone marrow. Furthermore, the uptake of 50-nm HEPC-containing liposomes by the bone marrow was specifically inhibited by preinjection of other liposomes, but not when they were exposed in advance to in vivo components. These observations suggest the involvement of in vivo component(s) in the uptake of these liposomes by the bone marrow. We conclude that small HEPC-liposomes with low Ch content show their significantly decreased uptake by the bone marrow due to their decreased recognition by this tissue.

In this study, we compared three gas compositions to determine if the duration of apnoea for SpO2 to decrease is proportionate to the oxygen fraction of the gas prior to apnoea. Twenty-five patients ASA physical status 1-2 aged two months to 12 years were included in the study. Anaesthesia was induced via a mask with 5% sevoflurane and 66% N2O in oxygen. After paralysis with vecuronium (0.12 mg.kg-1, i.v.) the trachea was intubated and anaesthesia was maintained with sevoflurane and N2O in oxygen. When cardiovascular stability was obtained, the patient was randomly set to breathe one of three gas compositions: 1. oxygen (FiO2 1.0), 2. N2O/O2 (FiO2 0.4), and 3. air/O2 (FiO2 0.4). All three gas compositions included 2-4% of sevoflurane to maintain anaesthesia. After more than eight min of each gas breathing, apnoea was begun by disconnecting the breathing circuit from the tracheal tube. The time from the start of apnoea (SpO2 100%) to SpO2 of 95% (T95) was measured. T95 measured after breathing N2O/O2 and air/O2 were 34.6 +/- 5.7 and 28.8 +/- 4.7% of that measured after oxygen breathing (P < 0.001 vs oxygen breathing, P < 0.001 vs oxygen and N2O/O2 breathing), respectively. Preoxygenation before intubation was validated to delay the haemoglobin desaturation brought about by apnoea. An induction technique using a low FiO2 will allow rapid haemoglobin desaturation.

Introduction New technology using partial carbon dioxide rebreathing has been developed to measure cardiac output. Because rebreathing increases respiratory effort, we investigated whether a newly developed system with 35 s rebreathing causes a lesser increase in respiratory effort under partial ventilatory support than does the conventional system with 50 s rebreathing. We also investigated whether the shorter rebreathing period affects the accuracy of cardiac output measurement. Method Once a total of 13 consecutive post-cardiac-surgery patients had recovered spontaneous breathing under pressure support ventilation, we applied a partial carbon dioxide rebreathing technique with rebreathing of 35 s and 50 s in a random order. We measured minute ventilation, and arterial and mixed venous carbon dioxide tension at the end of the normal breathing period and at the end of the rebreathing periods. We then measured cardiac output using the partial carbon dioxide rebreathing technique with the two rebreathing periods and using thermodilution.