Pharmacist Interventions for Adverse Drug Reactions in Palliative Care: A Multicentre Pilot Study.

This study aimed to investigate adverse reactions to medications administered during palliative care and compare the responses of Board-Certified Pharmacists in Palliative Pharmacy (BCPPP) and non-BCPPP professionals. Methods: This multicentre prospective survey included hospital and community pharmacists who are members of the Japanese Society for Pharmaceutical Palliative Care and Sciences. Study participants included patients who experienced new drug reactions during the study period and responded to the requested survey items. The follow-up period for each eligible patient began on the day the pharmacists initiated the intervention and ended at discharge, death, or after one month of intervention. The primary endpoint was the impact of pharmacist intervention on adverse drug reactions. The pharmacists included in the study evaluated the severity of adverse drug reactions to assess the effect of their intervention using an integrated palliative care outcome scale before and after the intervention. Key findings: During the survey period, 79 adverse drug reaction intervention reports from 69 patients were obtained from 54 pharmacists (28 certified and 26 non-certified). The response rate was 1.62% (54/3,343). The management of palliative pharmacotherapy side effects by BCPPP and non-BCPPP significantly improved the patients' activities of daily living (P < 0.001). The BCPPP group intervened for significantly more patients with adverse drug reactions and overall adverse drug reactions than the non-BCPPP group (P < 0.023 and P < 0.013, respectively). Conclusion: BCPPP interventions can improve symptom management.

Analysis of Urinary Retention Caused by Selective ß 3-adrenoceptor Agonists Using the Japanese Adverse Drug Event Report Database (JADER).

Overactive bladder (OAB) is a frequent chronic disorder which impairs quality of life by frequent, uncontrollable urination. Newly developed selectiveß 3-adrenoceptor agonists (sß 3-agonists) have the same efficacy in treating OAB but significantly fewer side effects than the traditionally used anti-muscarinics. However, safety data on these compounds are scarce. In this study, we analysed the occurrence of adverse effects in patients taking sß 3-agonists and their characteristics using the JADER database. The most frequently reported adverse effect associated with the use of sß 3-agonists was urinary retention [mirabegron; crude reporting odds ratios (ROR): 62.1, 95% confidence interval (CI): 52.0-73.6, P<0.001, vibegron; crude ROR: 250, 95% CI : 134-483, P<0.001]. Data from patients with urinary retention were stratified by sex. In both men and women, the rate of urinary retention was higher when using the mirabegron/anti-muscarinic drug when compared to mirabegron monotherapy; its occurrence was higher in men with a history of benign prostatic hypertrophy than in those without. Weibull analysis showed that approximately 50% of sß 3 agonist-induced urinary retention occurred within 15 days after initiation of treatment, and then gradually decreased. Although sß 3-agonists are useful against OAB, they may induce several side effects, especially urinary retention, which can further evolve into more severe conditions. Urinary retention occurs more frequently in patients concomitantly taking medication that either increases urethral resistance or has organic factors that block the urethra. When using sß 3-agonists, the concomitantly used medications and underlying diseases should be thoroughly reviewed, and safety monitoring should be instituted early during the treatment.

Early detection of Niemann-pick disease type C with cataplexy and orexin levels: continuous observation with and without Miglustat.

STUDY OBJECTIVES: Niemann-Pick type C (NPC) is an autosomal recessive and congenital neurological disorder characterized by the accumulation of cholesterol and glycosphingolipids. Symptoms include hepatosplenomegaly, vertical supranuclear saccadic palsy, ataxia, dystonia, and dementia. Some cases frequently display narcolepsy-like symptoms, including cataplexy which was reported in 26% of all NPC patients and was more often recorded among late-infantile onset (50%) and juvenile onset (38%) patients. In this current study, we examined CSF orexin levels in the 10 patients of NPC with and without cataplexy, which supports previous findings. METHODS: Ten patients with NPC were included in the study (5 males and 5 females). NPC diagnosis was biochemically confirmed in all 10 patients, from which 8 patients with NPC1 gene were identified. We compared CSF orexin levels among NPC, narcoleptic and idiopathic hypersomnia patients. RESULTS: Six NPC patients with cataplexy had low or intermediate orexin levels. In 4 cases without cataplexy, their orexin levels were normal. In 5 cases with Miglustat treatment, their symptoms stabilized or improved. For cases without Miglustat treatment, their conditions worsened generally. The CSF orexin levels of NPC patients were significantly higher than those of patients with narcolepsy-cataplexy and lower than those of patients with idiopathic hypersomnia, which was considered as the control group with normal CSF orexin levels. DISCUSSION: Our study indicates that orexin level measurements can be an early alert of potential NPC. Low or intermediate orexin levels could further decrease due to reduction in the neuronal function in the orexin system, accelerating the patients' NPC pathophysiology. However with Miglustat treatment, the orexin levels stabilized or improved, along with other general symptoms. Although the circuitry is unclear, this supports that orexin system is indeed involved in narcolepsy-cataplexy in NPC patients. CONCLUSION: The NPC patients with cataplexy had low or intermediate orexin levels. In the cases without cataplexy, their orexin levels were normal. Our study suggests that orexin measurements can serve as an early alert for potential NPC; furthermore, they could be a marker of therapy monitoring during a treatment.

Generation of pressures over 40 GPa using Kawai-type multi-anvil press with tungsten carbide anvils.

We have generated over 40 GPa pressures, namely, 43 and 44 GPa, at ambient temperature and 2000 K, respectively, using Kawai-type multi-anvil presses (KMAP) with tungsten carbide anvils for the first time. These high-pressure generations were achieved by combining the following pressure-generation techniques: (1) precisely aligned guide block systems, (2) high hardness of tungsten carbide, (3) tapering of second-stage anvil faces, (4) materials with high bulk modulus in a high-pressure cell, and (5) high heating efficiency.

Size control of sol-gel-synthesized ZnO quantum dots using photo-induced desorption.

We developed a sol-gel method using photo-induced desorption for size-controlled ZnO quantum dots (QDs). This method successfully controlled the size and size variance of ZnO QDs, and size fluctuations decreased from 23% to 18% depending on the illuminated light intensity. The sol-gel synthesis effectively reduced the number of defect levels that originated from oxygen defects.

In situ real-time monitoring of changes in the surface roughness during nonadiabatic optical near-field etching.

We performed in situ real-time monitoring of the change in surface roughness during self-organized optical near-field etching. During near-field etching of a silica substrate, we detected the scattered light intensity from a continuum wave (CW) laser (lambda = 633 nm) in addition to the etching CW laser (lambda = 532 nm) light source. We discovered that near-field etching not only decreases surface roughness, but also increases the number of scatterers, as was confirmed by analyzing the AFM image. These approaches provide optimization criteria for the etching parameter and hence for further decreases in surface roughness.

The effect of risperidone on D-amino acid oxidase activity as a hypothesis for a novel mechanism of action in the treatment of schizophrenia.

D-Amino acid oxidase (DAO) has been established to be involved in the oxidation of D-serine, an allosteric activator of the N-methyl-D-aspartate-type glutamate receptor in the brain, and to be associated with the onset of schizophrenia. The effect of risperidone, a benzisoxazole derivative, atypical antischizophrenic drug, on the activity of human DAO was tested using an in-vitro oxygraph system and rat C6, stable C6 transformant cells overexpressing mouse DAO (designated as C6/DAO) and pig kidney epithelial cells (LLC-PK(1)). Risperidone has a hyperbolic mixed-type inhibition, designated as 'partial uncompetitive inhibition effect', with K(i) value of 41 microM on human DAO. Risperidone exhibited a protective effect from D-amino acid induced cell death in both C6/DAO and LLC-PK(1) cells with 10% increase in viability. These data indicate the involvement of DAO activity in D-serine metabolism and also suggest a new mechanism of action to risperidone as antischizophrenic drug.

Exciton localization in vertically and laterally coupled GaN/AlN quantum dots.

Near-field and time-resolved photoluminescence measurements show evidence of exciton localization in vertically and laterally coupled GaN quantum dots (QDs). The binding energies in multiple period QDs (MQDs) are observed to be stronger by more than six times compared to single period QDs (SQDs). Excitons in MQDs have a short (450 ps) lifetime and persist at room temperature, while SQDs exhibit extraordinarily long (>5 ns) lifetime at 10 K due to reduced spatial overlap of electron and hole wave functions in strained QDs.

Excitation dynamics in a three-quantum dot system driven by optical near-field interaction: towards a nanometric photonic device.

Using density operator formalism, we discuss interdot excitation energy transfer dynamics driven by the optical near-field and phonon bath reservoir, as well as coherent excitation dynamics of a quantum dot system. As an effective interaction between quantum dots induced by the optical near-field, the projection operator method gives a renormalized dipole interaction, which is expressed as a sum of the Yukawa functions and is used as the optical near-field coupling of quantum dots. We examine one- and two-exciton dynamics of a three-quantum dot system suggesting a nanometric photonic switch, and numerically obtain a transfer time comparable with the recent experimental results for CuCl quantum dots.

Demonstrating nanophotonic switching using near-field pump-probe photoluminescence spectroscopy of CuCl quantum cubes.

We demonstrated a novel optical switching operation using three CuCl quantum cubes with a size ratio of. Their quantized excitonic energy levels resonate with one another, and the switching mechanism was based on the resonant near-field energy transfer between the quantum cubes. Using near-field pump-probe photoluminescence spectroscopy, we succeeded in controlling the near-field energy transfer and obtained a controlled (i.e. switched) signal in a differential photoluminescence spectrum with and without a pump beam. The internal quantum efficiency of the switching operation was close to 1. These results suggest the possibility of making a nanophotonic switching device smaller than 30 nm.

[Severe pulmonary edema in a preeclamptic patient with peripartum cardiomyopathy].

We report a preeclamptic patient who revealed severe pulmonary edema. A 37-year-old woman, at 32-week gestation, underwent emergency cesarean section under general anesthesia. She had no particular past medical history. SpO2 was 84% (room air) on the arrival at the operating room, and a chest X-ray showed pulmonary edema. She was managed in the intensive care unit postoperatively, she received an intensive treatment (positive pressure ventilation, furosemide, and inotropic support), and was extubated successfully on the third postoperative day. From clinical course and echocardiographic findings, we consider that this pulmonary edema was caused by peripartum cardiomyopathy.

[Endotoxin adsorption and continuous hemodiafiltration in three septic patients].

We report 3 patients in septic shock with panperitonitis. Endotoxin adsorption by polymixin B affinity column (PMX) and continuous hemodiafiltration (CHDF) were performed immediately after the surgery. Septic shock was not improved in patient 1 and 2 despite intensive care. Multimodal approach, including complete surgical repair, cardiovascular support and blood purification methods, is essential in treating septic patients.

Eyelid reconstruction using a hard palate mucoperiosteal graft combined with a V-Y subcutaneously pedicled flap.

Full-thickness eyelid defects after tumour ablation require the reconstruction of two layers, the anterior and posterior lamellae. Eyelids were successfully reconstructed after removal of malignant tumours in four patients using a hard palate mucoperiosteal graft combined with a curved V-Y subcutaneously pedicled flap. Although there have been some reports of hard palate mucosal grafts for reconstruction of the posterior lamella, the graft is not sufficiently rigid to support the reconstructed eyelid without the aid of supporting materials such as cartilage grafts. The hard palate mucoperiosteal graft seems to be rigid enough to support the reconstructed eyelid without the use of cartilage or other supporting materials. The subcutaneously pedicled V-Y advancement flap is useful for reconstruction of the anterior lamella in partial eyelid defects. We used it with a modified curved design to allow easy advancement and to make postoperative scars inconspicuous.

Second-harmonic generation in a near-field optical-fiber probe.

Second-harmonic generation (SHG) in a near-field optical-fiber probe was observed. The tip of the probe consists of a triple-tapered fiber with an aluminum coating. For a fiber probe with an aperture size of 100 nm, the SHG conversion factor was 2.0 x 10(-11)cm(2)/W , which is as large as that of a 5-mm KDP crystal. In a probe-to-probe experiment, we demonstrated that SHG took place at the aluminum coating on the fiber probe.

[Anesthesia for emergency surgery in 2 extremely low birth weight infants with ileus].

Two extremely-low-birth-weight infants, weighing each 684 and 975 g at birth, underwent emergency surgery because of ileus. Our previous experience with an extremely low birth weight infant, whose hemodynamic control during the surgery had been difficult without administering extra preoperative fluid and transfusion, made us administer enough fluid and transfusion during operation although their urine output was more than 2 ml.kg-1.hr-1. We gave intravenous volume to the present 2 cases before the operations despite the level of preoperative urine output and made their hemodynamic situation more stable during surgeries. We conclude it is very important to administer some amounts of intravenous volume (approximately 8-12 ml.kg-1.hr-1) in extremely low birth weight infants for emergency surgery with ileus regardless of their preoperative urine output.

[A review of correlation between transfusion rate of irradiated blood and potassium load].

Transfusion of the irradiated blood has become popular in Japan to prevent the graft-versus-host disease. Case reports, however, of hyperkalemic death or lethal ECG change have been increasing since the irradiated blood was introduced nation-wide. The potassium concentration of the supernatant of irradiated blood becomes about 60 mEq.l-1 by the end of storage period. If the potassium concentration is 60 mEq.l-1, the estimated safe transfusion rate would be 6 ml.min-1 and this can not be agreed with by clinicians who transfuse daily in cases of massive bleeding. The calculated safe transfusion rate (10 mEq.hr-1 of potassium load) ranges from 6 to 72 ml.min-1 considering the storage period from the day of gathering and irradiation. This difference could affect the survival rate. On the other hand, only the difference of the potassium concentration in the supernatant between the irradiated blood and the non-irradiated blood could not explain the increasing number of hyperkalemic case report. The mechanical factors may be related to hemolysis that causes extreme hyperkalemia. Control studies of proper transfusion rate of irradiated blood should be performed to establish a safety guideline for rapid transfusion of irradiated blood.

[Depressive effects of propofol on apoptotic injury and delayed neuronal death after forebrain ischemia in the rat--comparison with nitrous oxide-oxygen-isoflurane].

We investigated the brain protection effects of propofol anesthesia and nitrous oxide-oxygen-isoflurane anesthesia (GOI) using forebrain ischemic model of male Sprague-Dawley rats. Propofol group (P, n = 15) was anesthetized with propofol, oxygen and nitrogen (FIO2 = 0.33), and isoflurane group (GOI, n = 15) with 66% nitrous oxide, 33% oxygen and 1.2% isoflurane under mechanical ventilation. The anesthesia was deepened until electroencephalographic burst suppression appeared in each group. The bilateral common carotid arteries were, then, occluded for 10 minutes while the blood pressure was maintained at about 40 mmHg by venesection. The venesected blood was returned at the end of ischemic period. The animals were kept and fed in cage after emergence. On the day 2, 4, and 7, five animals of each group were sacrificed and the microscopic samples were obtained. The CA-1 cells of hippocampus were then stained with hematoxylin and eosin for the delayed neuronal death (DND) and with TUNEL method for the apoptosis. Propofol reduced the apoptosis, i.e., reduced the TUNEL positive cell count (GOI = 121.2 +/- 25.2.mm-1; P = 53.8 +/- 11.4.mm-1; P < 0.01; mean +/- SD) on the day 2 after ischemia, and also reduced the delayed neuronal death (alive CA-1 cell count; GOI = 18.1 +/- 8.9.mm-1; P = 33.1 +/- 12.8.mm-1; P < 0.01) on the day 7 after ischemia. It is important to determine the recovery interval after brain ischemia in detection of DND and apoptosis. We conclude that propofol inhibits neuronal apoptosis after brain ischemia and consequently reduces the delayed neuronal death in the CA-1 pyramidal cell layer of the hippocampus.

Acute production of vascular superoxide by angiotensin II but not by catecholamines.

OBJECTIVE: To determine whether vascular superoxide is rapidly released by angiotensin II and is involved in vascular contraction. DESIGN: The effect of superoxide dismutase (SOD) on angiotensin II induced elevation of mean arterial blood pressure was measured. Subsequently, acute production of vascular superoxide by angiotensin II and its effect on isometric tension were measured in rat aortic rings. The effects of catecholamines were concomitantly measured. METHODS AND RESULTS: The acute pressor effects of angiotensin II were significantly reduced when rats were pretreated intravenously with SOD. When angiotensin II was added on aortic segments in the presence of Cypridina luciferin analog, immediate elevations of chemiluminescence were observed which were inhibited by SOD. Furthermore, angiotensin II-induced elevations of isometric tension in aortic rings were significantly reduced by SOD. The effects of epinephrine and norepinephrine were concomitantly measured and were not significant CONCLUSIONS: The acute superoxide producing effect is likely to be specific to angiotensin II, because such a significant modification of the effects was not observed for catecholamines. Our results suggest that angiotensin II causes acute vascular superoxide production, which may be involved in the acute pressor effects.

Involvement of superoxide in acute reaction of angiotensin II in mesenteric microcirculation.

Superfusion of angiotensin II (Ang II) ceased blood flow in rat mesenteric microcirculation, however, successive reflow occurred. When nitric oxide synthase inhibitor was present, the stoppage of flow occurred by the lower concentration of Ang II. Superoxide dismutase (SOD) significantly delayed the stoppage by Ang II and restored the successive reflow earlier. The acute reaction between Ang II and mesenteric artery induced immediate superoxide (O(2)(-)) production when observed by a chemiluminescence method using the Cypridina luciferin analog. The acute vascular O(2)(-) production on the addition of Ang II contributed to in vitro vascular contraction as it was significantly attenuated by SOD. The acute superoxide-producing effect is likely to be specific to Ang II because such significant modification by SOD was not observed for norepinephrine.

Reaction of neuronal nitric oxide synthase with the nitric oxide spin-trapping agent, iron complexed with N-dithiocarboxysarcosine.

A water-soluble iron complex with N-dithiocarboxysarcosine (Fe-DTCS) has been developed as an ESR spin-trapping agent for NO and successfully applied to ESR imaging of endogenous NO production in mice. We attempted to measure NO produced by purified neuronal NO synthase (nNOS) by this method, but could not detect NO. We speculated that Fe-DTCS inhibits NOS activity. In fact, it markedly inhibited NOS activity with an IC50 value of 9.7 +/- 0.7 microM in the citrulline-formation assay. DTCS alone did not inhibit the activity. An iron complex with N-methyl-D-glucamine dithiocarbamate, a similar spin-trapping agent for NO, also inhibited the activity, with an IC50 value of 25.1 +/- 2.9 microM. Fe-DTCS suppressed cytochrome c and ferricyanide reductase activities of nNOS, and markedly increased nNOS-mediated NADPH oxidation. Concomitantly, it accelerated oxygen consumption caused by activated nNOS. These results suggest that the ESR spin-trapping agent Fe-DTCS inhibits NO synthesis by interfering with the physiological electron flow from NADPH to nNOS heme iron.