Current status of integrating oncology and palliative care in Japan: a nationwide survey.

BACKGROUND: Palliative care (PC) is increasingly recognized as essential for oncology care, and several academic societies strongly recommend integrating oncology and palliative care (IOP) in daily practice. Similarly, the Japanese government encouraged the implementation of IOP through the Cancer Control Act of 2007; however, its detailed progress remains unclear. Therefore, this cross-sectional nationwide survey was conducted to investigate the current status and hospital executive physicians' perception of IOP. METHODS: The questionnaire was developed based on IOP indicators with international consensus. It was distributed to executive physicians at all government-designated cancer hospitals (DCHs, n = 399) and matched non-DCHs (n = 478) in November 2017 and the results were compared. RESULTS: In total, 269 (67.4%) DCHs and 259 (54.2%) non-DCHs responded. The number of PC resources in DCHs was significantly higher than those in non-DCHs (e.g., full-time PC physicians and nurses, 52.8% vs. 14.0%, p < 0.001; availability of outpatient PC service ≥3 days per week, 47.6% vs. 20.7%, p < 0.001). Routine symptom screening was more frequently performed in DCHs than in non-DCHs (65.1% vs. 34.7%, p < 0.001). Automatic trigger for PC referral availability was limited (e.g., referral using time trigger, 14.9% vs. 15.3%, p = 0.700). Education and research opportunities were seriously limited in both types of hospitals. Most executive physicians regarded IOP as beneficial for their patients (95.9% vs. 94.7%, p = 0.163) and were willing to facilitate an early referral to PC services (54.7% vs. 60.0%, p < 0.569); however, the majority faced challenges to increase the number of full-time PC staff, and < 30% were planning to increase the staff members. CONCLUSIONS: This survey highlighted a considerable number of IOP indicators met, particularly in DCHs probably due to the government policy. Further efforts are needed to address the serious research/educational gaps.

Changes in nitric oxide production and cerebral blood flow before development of hyperbaric oxygen-induced seizures in rats.

The predictive value of increase in cerebral blood flow (CBF) was examined to detect hyperbaric oxygen (HBO(2))-induced electrical discharge in artificially ventilated rats at three PaCO(2) levels under 5 atmospheric pressures. The possible involvement of NO production in the mechanism of the increase in CBF was also assessed by measurement of major NO metabolites (NO(2)(-) plus NO(3)(-)) using a microdialysis technique at the left parietal cortex during HBO(2) exposure. The onset times of electrical discharge, measured in the right frontal region, were significantly prolonged and shortened in the low PaCO(2) group (79+/-21 min) and high PaCO(2) group (27+/-7 min), respectively, compared to that in the normal PaCO(2) group (37+/-5 min). Increase in CBF (200% of the pre-exposure level) was observed in every animal and was sustained until the appearance of electrical discharge. The onset time of increase in CBF was closely related to that of electrical discharge (R(2)=0.987), and the durations of increase in CBF were almost identical (11-14 min in mean) regardless of the PaCO(2) level. The level of NO(2)(-) plus NO(3)(-) was unaffected by the initiation of HBO(2) exposure and simultaneously increased up to 246+/-59% of control level with the onset of increase in CBF. There was a close relationship between changes in CBF and levels of NO(2)(-) plus NO(3)(-) (R(2)=0.544). These results indicate that monitoring of CBF is useful for the prediction of electrical discharge in artificially ventilated rats regardless of their PaCO(2) levels and that the increase in NO production is related to the mechanism of increase in CBF.

[A case of central retinal artery occlusion after anterior posterior fusion of the lumbar spine].

We report a case of central retinal artery occlusion after anterior-posterior fusion of the lumbar spine. The patient suddenly lost his vision of the right eye in the ICU just after the end of long procedure for anterior-posterior fusion of the lumbar spine. The patient was diagnosed as having central retinal artery occlusion, and treated successfully with treatments including immediate administration of urokinase and PGE1, stellate ganglion block, and hyperbaric oxygen therapy. The patient was discharged from the hospital on the 54th postoperative day with adequate vision to drive a car. Central retinal artery occlusion is a rare but very serious complication during and after supine surgery with prone position. It is very important for us to be aware of its possible occurrence. We have to diagnose and treat, as soon as possible, the vision loss after the spine surgery.

Hyperbaric oxygen reduces infarct volume in rats by increasing oxygen supply to the ischemic periphery.

OBJECTIVE: Hyperbaric oxygen (HBO) increases oxygen supply to anoxic areas. To examine the therapeutic effect of HBO on ischemic stroke, we measured infarct volume as well as cerebral blood flow (CBF), oxygen supply, and lipid peroxidation in the ischemic periphery. DESIGN: Prospective experimental study in rats. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Thirty-eight adult rats. INTERVENTION: The rats were anesthetized (1% halothane) and intubated. Focal ischemia was induced by ligating the right middle cerebral and right common carotid arteries. Nineteen animals were exposed to 2 hrs of HBO (100% oxygen, 3 atmospheres absolute), initiated 10 mins after the onset of ischemia. The remaining animals were kept at ambient pressure and used as controls. MEASUREMENTS AND MAIN RESULTS: At the initiation of ischemia, CBF measured by a laser-Doppler flow probe placed in the ischemic periphery was reduced to 47%+/-11% and 51%+/-15% of normal levels in animals exposed or not to HBO, respectively. These altered values were not affected further by administration of HBO and remained stable throughout a 2-hr observation period. Arterial oxygen pressure and content were significantly increased to 1571+/-130 torr (209.41+/-17.32 kPa; p < .0001) and 1.03+/-0.04 mmol/dL (p < 0.0001), respectively, in HBO-treated animals compared with nontreated animals (139+/-14 torr [18.53+/-1.87 kPa] and 0.86+/-0.04 mmol/dL, respectively). The calculated increase in the oxygen supply to the ischemic periphery was 20%. The infarct volume of HBO-treated animals measured 24 hrs after the onset of focal cerebral ischemia was significantly reduced by 18% (HBO-treated, 132+/-13 mm3 vs. nontreated, 161+/-29 mm3; p = .02). Lipid peroxidation was unchanged after 120 mins of HBO administration in the cerebral cortex where the laser-Doppler flow probe was placed. CONCLUSIONS: HBO at 3 atmospheres absolute reduced infarct volume by increasing oxygen supply to the ischemic periphery without aggravating lipid peroxidation, suggesting that HBO can be useful in treating stroke victims.

Contrast medium-induced pulmonary edema is aggravated by silicone contamination in rats.

PURPOSE: To examine the effect of silicone contamination, which occurs in clinical settings during vial preparation with disposable syringes, on contrast medium-induced pulmonary edema in rats. MATERIALS AND METHODS: Ioxaglate, ioversol, and iohexol, silicone-containing physiologic saline solutions, and three silicone-containing contrast media were separately, intravenously injected at 1.5 mL/min in rats. Pulmonary edema was evaluated as changes in the relative lung weight and in the water, sodium, and potassium contents of the lung. RESULTS: Intravenous injection of ioxaglate induced marked pulmonary edema, even with a dose of only 4 g of iodine per kilogram of body weight. In contrast, ioversol and iohexol induced significant pulmonary edema only after the injection of large doses (6 g of iodine per kilogram; P < .05). The injection of 4 microL/mL silicone-containing physiologic saline at a dose of 18.75 mL/kg also produced marked pulmonary edema, whereas doses of 6.25 and 12.5 mL/kg showed no significant influence. The addition of an ineffective dose (12.5 mL of physiologic saline per kilogram of body weight) of silicone in contrast medium substantially aggravated the pulmonary edema induced by the contrast medium alone; this phenomenon was also confirmed with morphologic observation. CONCLUSION: Ionic contrast media are more toxic to the endothelial cells than are nonionic contrast media. Silicone contamination might be one of the causes of pulmonary edema after intravenous injection. However, caution must be exercised in extrapolating these results to humans.

Effect of hyperbaric oxygenation on the Na+, K(+)-ATPase and membrane fluidity of cerebrocortical membranes after experimental subarachnoid hemorrhage.

It is reported that CNS hemorrhage causes membrane dysfunction and may exacerbate this damage as a result of secondary ischemia or hypoxia. Since hyperbaric oxygenation improves oxygen metabolism, it may reduce this membrane damage. The present study was conducted to reveal whether hyperbaric oxygenation influences membrane alteration after hemorrhage. Thirty minutes after subarachnoid hemorrhage induction, rats were treated with hyperbaric oxygenation 2 ATA for 1 hour. Rats were decapitated 2 hours after subarachnoid hemorrhage induction. Na+, K(+)-ATPase activity measurement and spin-label studies were performed on crude synaptosomal membranes. Subarachnoid hemorrhage decreased Na+, K(+)-ATPase activity. Spin label studies showed that hydrophobic portions of near the membrane surface became more rigid and the mobility of the membrane protein labeled sulfhydryl groups decreased after subarachnoid hemorrhage. Hyperbaric oxygenation significantly ameliorated most of the subarachnoid hemorrhage induced alterations. We conclude that hyperbaric oxygenation may be a beneficial treatment for acute subarachnoid hemorrhage.

Microinjection of alpha-calcitonin gene-related peptide into the hypothalamus activates sympathetic outflow in rats.

Effect of rat alpha-calcitonin gene-related peptide (alpha-CGRP) microinjected into various hypothalamic nuclei on plasma levels of catecholamines and arterial blood pressure were investigated in urethane-anesthetized rats. alpha-CGRP (0.05 and 0.25 nmol) microinjected into the hypothalamic paraventricular nucleus (PVN) increased the plasma level of noradrenaline (NA), but not that of adrenaline (AD), in a dose-dependent manner. A similar increase in plasma level of NA was also observed by alpha-CGRP (0.05 nmol) microinjected into the preoptic area (POA), anterior hypothalamus (AH), dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). A significant increase in arterial blood pressure was observed by microinjection of alpha-CGRP (0.05 nmol) into the PVN, POA, AH and DMH, and the most prominent increase was caused by its microinjection into the PVN. Microinjection of the same dose of this peptide into the VMH, lateral hypothalamic area and posterior hypothalamus was without effect. The increase in plasma level of NA induced by alpha-CGRP (0.05 nmol) into the PVN was not affected by bilateral adrenalectomy. Electrical stimulation of the PVN elicited increases in plasma levels of both NA and AD. This increase in NA was abolished by chemical sympathectomy with 6-hydroxydopamine (50 mg/kg, i.v., 3 days before experiments). These results suggest that activation of the PVN by electrical stimulation elicits both sympathetic and adrenomedullary outflow. alpha-CGRP microinjected into the PVN selectively activates the sympathetic outflow.

Adrenaline absorption: effect of pH in mepivacaine and bupivacaine solutions. A clinical study during halothane anesthesia.

The effect of the pH of the solution on the rate of absorption into the blood stream of locally-injected adrenaline using an adrenaline solution mixed with either mepivacaine or bupivacaine was investigated. Forty patients undergoing elective craniotomy received one of the following five solutions for subcutaneous and subgaleaic injection in the dose 0.5 ml/kg: 1) mepivacaine-adrenaline (pH = 6.1), 2) mepivacaine-adrenaline (pH = 7.5), 3) bupivacaine-adrenaline (pH = 6.1), 4) bupivacaine-adrenaline (pH = 7.4), or 5) adrenaline (pH = 6.1). Both mepivacaine and bupivacaine added to the adrenaline solution increased the plasma concentration of adrenaline. Alkalinization attenuated the peak concentration of adrenaline in the case of a mepivacaine-adrenaline solution, but not in the case of a bupivacaine-adrenaline solution.

Halothane impairs the bioenergetic functions of isolated rat liver mitochondria.

The effect of halothane, a potent and popular volatile anesthetic, on isolated rat liver mitochondria was examined. Halothane inhibited state 3 and dinitrophenol-induced uncoupled respiration with NAD(+)-linked substrates, but not with FAD-linked substrates, and did not affect the oxidation-reduction state of mitochondrial cytochromes. Moreover, halothane increased state 4 respiration and ATPase activity and decreased the extra-mitochrondrial pH change coupled to ATP synthesis. These results indicate that halothane impairs mitochondrial ATP production by interfering with both the electron transport from NAD+ to FAD and the coupling of oxidative phosphorylation. Halothane only slightly affected the membrane potential, which is commonly dissipated by typical classical uncouplers. Moreover, halothane inhibited both ATP-driven and respiration-driven Ca2+ accumulation in mitochondria and stimulated Ca2+ release from mitochondrial stores at concentrations higher than those at which it inhibited ATP production. These findings indicate that the uncoupling action of halothane is not classical. During halothane anesthesia, these mitochondrial abnormalities may contribute to hepatocyte dysfunctions.