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Opioid analgesics play a central role in cancer pain treatment; however, it has been reported that opioid-induced constipation (OIC) develops in 80% of patients using opioid analgesics and leads to a decrease in quality of life. Naldemedine improves constipation without affecting the analgesic action of opioid analgesics via peripheral μ-opioid receptors.
We report a terminally ill cancer patient who was diagnosed with opioid withdrawal syndrome (OWS) based on symptoms centered around restlessness and sweating that developed 43 days after administration of naldemedine for OIC.
The patient was a 78-year-old woman who was diagnosed with stage IVB uterine sarcoma in October, 1 year prior to her visit to our clinic, and underwent chemotherapy after surgery, but the disease became progressive. Thereafter, metastasis to the fourth thoracic vertebrae (Th4) was identified, and loxoprofen and acetaminophen were started for pain at the metastatic site. Oxycodone hydrochloride hydrate 10 mg/day was additionally administered on postoperative day 11, followed by naldemedine 0.2 mg/day for OIC. On the 43rd day after administration, the patient began to wander the hospital ward in a wheelchair and became noticeably restless. OWS due to naldemedine administration was suspected, and naldemedine was discontinued. The symptoms improved 7 days later, and no similar symptoms were observed thereafter.
Significance of results
Patients receiving palliative care often exhibit psychiatric symptoms such as anxiety and depression, but OWS due to naldemedine should also be considered as a potential cause.
One of the side effects of opioid administration is opioid-induced constipation (OIC). To address this side effect, the oral peripheral μ opioid receptor antagonist naldemedine was developed. As this drug does not cross the blood–brain barrier, it is thought that it does not lead to opioid withdrawal syndrome (OWS) with central nervous system symptoms.
Here, we report a cancer patient who presented with symptoms centered round anxiety and irritation 4 months after administration of naldemedine for OIC and who was diagnosed with OWS after close investigation.
The patient was a 65-year-old female who had surgery for stage IB endometrial cancer 4 years previously, but experienced recurrence involving the pelvis 2 years later. Medical narcotics were used to control pain, but naldemedine was started to control subsequent constipation. When naldemedine-related OWS was suspected and the administration of naldemedine discontinued, the above symptoms disappeared within two days, and no recurrence was observed thereafter.
Significance of the results
For patients receiving naldemedine, it is necessary to consider the possibility of OWS regardless of the period of administration in order to maintain patient quality of life.
Thiamine deficiency (TD) is recognized in various kinds of disease with associated loss of appetite including cancer. However, it has not been recognized to date in bereaved partners after spousal loss from cancer.
From a series of bereaved partners who lost a spouse to cancer, we report on those who developed TD after bereavement.
Case 1 was a 57-year-old woman who sought consultation at our “bereavement clinic.” Her husband had been diagnosed with pancreatic cancer one year earlier and had died one month previously. At the first visit, she was observed to suffer depression, anxiety, and decreased appetite. Neurological, blood, and biochemical examinations did not reveal any noteworthy findings. She was diagnosed with uncomplicated bereavement. Detailed examination revealed that her appetite had been markedly decreased for approximately five weeks. The diagnosis of TD was supported by her abnormally low serum thiamine level. Case 2 was a bereaved 73-year-old male who had lost his wife to hypopharyngeal cancer one month previously after a five-year illness. He had shown a lack of energy for the month preceding his wife's death, but because there was no improvement after her death, his family recommended he seek consultation at our “bereavement clinic.” He was suffering from major depressive disorder. Detailed examination revealed that his appetite had been decreased for more than two weeks. Again, the diagnosis of TD was supported by his abnormally low serum thiamine level.
Significance of results
These reports demonstrate that there is a possibility that bereaved could develop TD after the loss of a loved one. TD should be considered whenever there is a loss of appetite lasting for more than 2 weeks, and medical staff should pay careful attention to the physical condition of the bereaved to prevent complications because of TD.
Thiamine deficiency (TD) is recognized in various kinds of disease with associated loss of appetite including cancer; however, TD has not been recognized in the family caregivers of cancer patients to date.
From a series of cancer patient caregivers, we reported an aged family caregiver who developed TD while caring for the cancer patient.
The caregiver was a 90-year-old male. He had been accompanying his wife, who was diagnosed with colon cancer 4 years previously, on hospital visits as the primary caregiver, but because of psychological issues, he was recommended to visit the psycho-oncology department's “caregiver's clinic” for a consultation. Detailed examination revealed that his appetite had been only about 50% of usual from about one year before, and he had lost 12 kg in weight in one year. The diagnosis of TD was supported by his abnormally low serum thiamine level.
Significance of the results
This report demonstrates that there is a possibility that care providers could develop TD from the burdens associated with caregiving. TD should be considered whenever there is a loss of appetite lasting for more than 2 weeks, and medical staff should pay careful attention to the physical condition of care providers to prevent complications resulting from TD.
Wernicke encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine deficiency, and is sometimes overlooked because of the diversity of clinical symptoms.
From a series of WE patients with cancer, we report a lung cancer patient who developed WE, the main symptom of which was agitation.
A 50-year-old woman with lung cancer was referred to our psycho-oncology clinic because of agitation lasting for three days. No laboratory findings or drugs explaining her agitation were identified. Although the patient did not develop delirium, ophthalmoplegia, or ataxia, WE was suspected because she experienced a loss of appetite loss lasting 5 weeks. This diagnosis was supported by abnormal serum thiamine and disappearance of agitation one hour after intravenous thiamine administration.
Significance of results
This report emphasizes the clinical diversity of WE and indicates the limits of the ability to diagnose WE from typical clinical symptoms. The presence of a loss of appetite for more than two weeks may be the key to the accurate diagnosis of WE.
Wernicke's encephalopathy (WE) is a neuropsychiatric disorder caused by a thiamine deficiency. Although WE has been recognized in cancer patients, it can be overlooked because many patients do not exhibit symptoms that are typical of WE, such as delirium, ataxia, or ocular palsy. Furthermore, outpatients with WE who intermittently present at psycho-oncology clinics have not been described as far as we can ascertain.
This report describes two patients who did not exhibit the complete classic triad of symptoms among a series with cancer and WE, and who attended a psycho-oncology outpatient clinic.
Case 1, a 76-year-old woman with pancreatic cancer and liver metastasis, periodically attended a psycho-oncology outpatient clinic. She presented with delirium and ataxia as well as appetite loss that had persisted for 8 weeks. We suspected WE, which was confirmed by low serum thiamine levels and the disappearance of delirium after thiamine administration. Case 2, a 79-year-old man with advanced stomach cancer, was referred to a psycho-oncology outpatient clinic with depression that had persisted for about 1 month. He also had appetite loss that had persisted for several weeks. He became delirious during the first visit to the outpatient clinic. Our initial suspicion of WE was confirmed by low serum thiamine levels and the disappearance of delirium after thiamine administration. The key indicator of a diagnosis of WE in both patients was appetite loss.
Significance of results
This report emphasizes awareness of WE in the outpatient setting, even when patients do not exhibit the classical triad of WE. Appetite loss might be the key to a diagnosis of WE in the absence of other causes of delirium.
Thiamine is an essential coenzyme for oxidative metabolisms; however, it is not synthesized in the human body, and the average thiamine storage capacity is approximately 18 days. Therefore, thiamine deficiency (TD) can occur in any condition of unbalanced nutrition. If TD is left untreated, it causes the neuropsychiatric disorder Wernicke encephalopathy (WE). Although WE is a medical emergency, it is sometimes overlooked because most patients with WE do not exhibit all of the typical symptoms, including delirium, ataxia, and ophthalmoplegia. If all of the typical clinical symptoms of WE are absent, diagnosis of TD or WE becomes more difficult.
From a series of cancer patients, we reported three patients who developed TD without the typical clinical symptoms of WE.
A 69-year-old woman with pancreatic body cancer receiving chemotherapy with paclitaxel and gemcitabine for six months. Her performance status (PS) was 1. A detailed interview revealed that she had appetite loss for six months. Another 69-year-old woman with ovarian cancer received nedaplatin; her PS was 0. A detailed interview revealed that she had appetite loss for three months. A 67-year-old woman with colon cancer receiving ramucirumab in combination with second-line fluorouracil with folinic acid and irinotecan. Her PS was 1. A detailed interview revealed that she had appetite loss for three weeks. None exhibited typical clinical signs of WE, but they developed appetite loss for six months, three months, and three weeks, respectively. The diagnosis of TD was supported by abnormally low serum thiamine levels.
Significance of the results
This report emphasizes the possibility of TD in cancer patients even when patients do not develop typical clinical signs of WE. The presence of appetite loss for more than two weeks may aid in diagnosing TD. Patients receiving chemotherapy may be at greater risk for developing TD.
Wernicke encephalopathy (WE) is a neuropsychiatric disorder caused by thiamine deficiency. Several reports of WE in cancer patients are known. WE is sometimes overlooked because most patients do not exhibit its typical symptoms (e.g., delirium, ataxia, ocular palsy). If delirium is not present, a diagnosis of WE is difficult because delirium is the hallmark symptom of WE.
Taken from a series on WE in cancer, we report two patients who developed WE without delirium during periodic psycho-oncology outpatient visits.
Case 1. A 61-year-old woman with non-Hodgkin lymphoma who was periodically attending a psycho-oncology outpatient clinic developed an unsteady gait. WE was suspected because she also developed appetite loss for two weeks, and we could find no other laboratory findings to explain her unsteady gait. Our diagnosis was supported by abnormal serum thiamine and disappearance of the gait disturbance after intravenous thiamine administration. Case 2. A 50-year-old woman with breast carcinoma with bone metastasis developed an unsteady gait. WE was suspected because she also developed loss of appetite for two weeks, and no other laboratory findings could explain her unsteady gait. The diagnosis was supported by abnormal serum thiamine and disappearance of the gait disturbance after administration of intravenous thiamine.
Significance of Results:
Our report emphasizes the importance of being aware of WE, even when patients do not present with delirium. The presence of loss of appetite for more than two weeks may be the key to a diagnosis of WE.
The death of a loved one is one of the most stressful events of life, and such stress affects the physical and psychological well-being of the bereaved. Dissociative amnesia is characterized by an inability to recall important autobiographical information. Dissociative amnesia in the bereaved who have lost a loved one to cancer has not been previously reported. We discuss herein the case of a patient who developed dissociative amnesia the day after the death of here beloved husband.
A 38-year-old woman was referred for psychiatric consultation because of restlessness and abnormal behavior. Her 44-year-old husband had died of pancreatic cancer the day before the consultation. On the day of the death, she looked upset and began to hyperventilate. The next day, she behaved as if the deceased were still alive, which embarrassed her family. At her initial psychiatric consultation, she talked and behaved as if her husband was still alive and in the hospital.
Her psychiatric features fulfilled the DSM–V criteria for dissociative amnesia. The death of her husband had been very traumatic for her and was considered to have been one of the causes of this dissociation.
Significance of Results:
This report adds to the list of psychiatric symptoms in the bereaved who have lost a loved one to cancer. In an oncology setting, we should consider the impact of death, the concomitant defense mechanisms, and the background of the families.
Many curious white spots of 1–10 cm diameter were found on wet snow (~10 mm thick) on the morning of 1 November 2009 in Kitami and Oketo in Hokkaido, Japan. At first glance, the white spots appeared to be made of spherically gathered snow; however, they had actually been formed by the scattering of sunlight over wet snow. Thin air bubbles enclosed in the wet snow caused a diffuse reflection of sunlight and formed the white spots. We refer to this phenomenon as white spotted wet snow. Although this type of snow has been briefly described previously, the formation process, meteorological conditions that lead to its formation, its vertical structure and the horizontal distribution of the white spots are unknown. Our study addresses these issues. In addition, three independent methods (a nearest-neighbour method, Voronoi diagram and two-dimensional correlation function) demonstrate that the white spots are not randomly distributed but tend to be surrounded by six other spots.
Following an International Geophysical Year project, we conducted meteorological observations during 2004–07 around the Suntar–Khayata range in eastern Siberia, where a strong temperature inversion exists throughout the winter. The temperature on the flat plain around Oymyakon (~700ma.s.l.) was ~20°C lower than that in a glaciated area located at ~2000ma.s.l. The inversion remained stable from October to April due to the Siberian high. Snowfall was limited to the beginning and end of winter. The stable conditions prevented atmospheric disturbances and inhibited snowfall during midwinter. From 1945 to 2003, glaciers in the Suntar–Khayata range retreated, with an area reduction of 19.3%. To assess this retreat, we estimated the response of the glaciers to climate change. According to US National Centers for Environmental Prediction (NCEP) data, the temperature in this region increased by ~1.9°C over 60 years. By calculating snow accumulation and ablation, the sensitivity of the equilibrium-line altitude (ELA) to the temperature shift was evaluated. We estimated snow precipitation based on precipitation at <0°C and ablation using the degree-day method. By these estimates, the ELA of Glacier No. 31, assumed 2350 m at present, could rise ~150m if temperature rises an average of 1°C. Furthermore, a 1.8°C temperature rise could cause the ELA to rise to 2600ma.s.l., removing the accumulation zone. With no accumulation zone, the glacier body would decrease, roughly halving in volume after ~400 years.
We developed allometric relationships between tree size parameters (stem diameter at breast height (dbh), at ground surface (D0) and tree height) and leaf, stem, small-root (diameter <5 mm) and total root biomass in various tropical secondary-forest trees in Sarawak, Malaysia. In total, 136 individuals from 23 species were harvested to measure above-ground parts. Root systems of 77 individuals of 16 species were also excavated. The coefficients of correlation for the obtained allometric relationships between tree diameter and plant-part biomass showed high values, ranging from 0.83 to 0.99. In addition, there were few interspecific differences in relationships for all biomass parts, except for leaves. We also found relatively high coefficients of allometric relationships between tree height and plant-part biomass ranging from 0.83 to 0.94. Comparison of above- and below-ground biomass equations for various tropical rainforests implies that our allometric equations differ largely from the equations for tropical primary forests. Thus, choosing both above- and below-ground allometric equations for biomass estimation in tropical secondary forests of South-East Asia requires careful consideration of their suitability.
The surface mass balance (SMB) at Dome Fuji, East Antarctica, was estimated using 36 bamboo stakes (grid of 6 × 6, placed at 20 m intervals) from 1995 to 2006. The heights of the stake tops from the snow surface were measured at 0.5 cm resolution twice monthly in 1995, 1996, 1997 and 2003, and once a year for the rest of the study period. To account for snow settling, the average snow density at the stake base during the measurements was used for converting the stake-height data to SMB. The annual SMB from 1995 to 2006 at Dome Fuji was 27.3 ± 1.5 kg m−2 a−1. This result agrees well with the annual SMB from AD 1260 to 1993 (26.4 kg m−2 a−1) estimated from volcanic signals in the Dome Fuji ice core. Over the period 1995–2006, there were 37 (8.6% of the measurements) negative or zero annual SMB results. Variation in the multi-year averages of annual SMB decreased with the square root of the number of observation years, and 10 years of observations of a single stake allowed the estimation of annual SMB at ±10% accuracy. The frequency distributions of annual and monthly SMB were examined. The findings clarify the complex behavior of the annual and monthly SMB at Dome Fuji, which will be common phenomena in areas of low snow accumulation of the interior of the Antarctic ice sheet.
To examine the validity and reproducibility of a self-administered food-frequency questionnaire (FFQ) used for two cohort studies in Japan.
Two rural towns in the Miyagi Prefecture, in north-eastern Japan.
Fifty-five men and 58 women.
A 40-item FFQ was administered twice, 1 year apart. In the mean time, four 3-day diet records (DRs) were collected in four seasons within the year. We calculated daily consumption of total energy and 15 nutrients, 40 food items and nine food groups from the FFQs and the DRs. We computed Spearman correlation coefficients between the FFQs and the DRs. With adjustment for age, total energy and deattenuation for measurement error with the DRs, the correlation coefficients for nutrient intakes ranged from 0.25 to 0.58 in men and from 0.30 to 0.69 in women, with median of 0.43 and 0.43, respectively. Median (range) of the correlation coefficients was 0.35 (−0.30 to 0.72) in men and 0.34 (−0.06 to 0.75) in women for food items and 0.60 (−0.10 to 0.76) and 0.51 (0.28–0.70) for food groups, respectively. Median (range) of the correlation coefficients for the two FFQs administered 1 year apart was 0.49 (0.31–0.71) in men and 0.50 (0.40–0.64) in women for nutrients, 0.43 (0.14–0.76) and 0.45 (0.06–0.74) respectively for food items, and 0.50 (0.30–0.70) and 0.57 (0.39–0.66) respectively for food groups. Relatively higher agreement percentages for intakes of nutrients and food groups with high validity were obtained together with lower complete disagreement percentages.
The FFQ has a high reproducibility and a reasonably good validity, and is useful in assessing the usual intakes of nutrients, foods and food groups among a rural Japanese population.
A measure of snow density is required to estimate water equivalent ice-sheet surface mass balance (SMB) from stake measurements. Previous studies have utilized the snow density at different depths within the snow. By considering the snow densification process in the time interval between stake height measurements, we find that use of the snow density at the base of the stake is more appropriate. We assume the stakes are firmly anchored at the bottom and that Sorge’s law holds, i.e. the density–depth profile does not change with time. Applying this method to the data for 36 snow stakes on Dome Fuji, the SMB in 2003 was 36.5 kg m-2 a−1, 27% larger than the previous estimate, which used surface snow density. Correct selection of the snow density for SMB estimations is important, especially for Antarctic inland areas where accumulation is low (e.g. Dome Fuji, Vostok, Dome C and South Pole) and where the snow density near the surface varies markedly.
SPICA is a cooled, single large-mirror space-telescope, which is under discussion as an succsesor of the ASTRO-F mission. One of the most ambitious challenges of the SPICA mission is the direct observations of exoplanets with a coronagraph instrument. We report cryogenic infrared optics to realize high quality wavefronts for the SPICA coronagraph.
The SPICA satellite will be launched by an H-IIA rocket to Sun-Earth L2 Halo orbit early in the 2010s. The SPICA telescope is a Ritchey-Chretien optics with 3.5m diameter primary mirror, and cooled down to 4.5 K in orbit by radiation cooling and mechanical cryo-coolers. Main working wavelengths are 5–200 micron. Advantages of the SPICA coronagraph are the infrared wavelenths where the contrast between planets and central stars are smaller than the optical wavelengths, and that the cooled space telescope consists of monolithic mirrors.
Development of light-weight cooled telescope is one of the most important tasks to realize SPICA. At the present, sintered SiC and carbon fiber reinforced SiC (C/SiC) composite are candidate materials for the mirrors, truss, and optical bench. For these materials, estimations and improvements of basic property and surface roughness in cryogenic temperatures have been carried out. Deformation of trial product mirrors by cooling is also examined.
We are developing cryogenic deformable mirrors (DMs) because wave front accuracy of the SPICA telescope is 0.35 micron RMS, which is not enough for our coronagraphic instrument. For MEMS (Micro Electro Mechanical System) DM and some others, measurements of thermal deformation by cooling, electrical response, and heat generation are undergoing. Developments of a tip-tilt system for cryogenic usage started to cancel vibration caused by the cryo-coolers and other components and to realize a diffraction limit resolution. The first result of our binary mask coronagraph experiment is also shown.
The world's first microstereolithography named “IH process” was developed by Ikuta et al. in 1992. Several types of micro stereo lithography including Hybrid-IH process, Super-IH process and Two-photon IH process, have been also developed. Three-dimensional (3D) resolution has reached to 140 nm in the two-photon IH process. The super-IH process and the two-photon process enable direct writing of movable micromechanisms without assembling process or sacrificial layer technique. The hybrid-IH process provides various types of composite devices with other functional elements such as actuators and sensors. These IH processes can be widely used for making polymeric microdevices. We have applied these techniques to create new micro chemical device named “Biochemical IC Chip” proposed by Ikuta et al. in 1994. IH process enables to make the biochemical IC chip including real 3D micro fluidic channels. Various kinds of Biochemical IC chip such as micro pumps, switching valves, reactors, concentrators, have already been fabricated. In chip cell-free protein synthesis has been demonstrated by using biochemical IC chips. The biochemical IC chips will open new bioscience and medicine based on innovative technology. In this paper, we introduce several types of IH process and its application to biochemical IC chips.
A glacier at the summit of Ushkovsky volcano, Kamchatka peninsula, Russia, was studied in order to obtain information about the physical characteristics of a glacier that fills a volcanic crater. The glacier has a gentle surface and a concave basal profile with a maximum measured depth of 240 m at site K2. The annual accumulation rate was 0.54 m a−1 w.e., and the 10 m depth temperature was −15.8°C. A 211.70 m long ice core drilled at K2 indicates that (1) the site is categorized as a percolation zone, (2) the stress field in the glacier changes at 180 m depth from vertical and longitudinal compression with transversal extension, which is divergent flow, to a shear-dominated stress field, and (3) the frequent occurrence of ash layers can be a good tool for dating the ice core. The borehole temperature profiles were considered to be non-stationary, but the linear profile made it possible to estimate the basal temperature and the geothermal heat flux at K2. Assuming constant surface and the basal boundary conditions, we constructed two depth–age relationships at K2. These predicted that the bottom ages of the ice core were about 511 or 603 years.
A 2.2 m deep pit and the top 42.5 m of an ice core recovered at Snøfjellafonna, northwestern Spitsbergen, were continuously analyzed for Na+, Cl−, NO3−, SO42− and pH. Seasonal variations in ionic concentrations seem to have remained in the pit and the core, in spite of the relatively severe summer melting. We dated the core by counting annual peaks of Na+ and made an adjustment with the use of a tritium peak in 1963 as a reference horizon. It turned out that the depth of 42.5 m went back to the early 1930s or late 1920s. The 60–70 year record of snow chemistry showed that the concentrations of both NO3− and SO42− had increased in the 1950s and had decreased in the late 1970s and the 1980s. The increase would be explained in terms of anthropogenic inputs from the industrial areas. The later decrease of the same ions may have been caused by a combination of the reduction of the atmospheric precursors due to pollution controls and the meltwater-associated processes.
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