Discrepancies between Reasons of Palliative Care Team Consultation and Palliative Care Team Activities.

BACKGROUND: Palliative care team (PCT) is a common type of palliative care services. However, distress in cancer patients may be underestimated by hospital staff. Reasons for PCT consultation may be inconsistent with patients' actual needs. OBJECTIVE: We aimed to examine the proportions of discrepancy between the reasons for PCT consultation and actual PCT activities. DESIGN AND METHODS: We performed an observational study based on datasets of PCT activities at Kindai University Hospital. Differences in the proportion between reasons for PCT consultation and actual PCT activities were calculated. RESULTS: Datasets of 368 hospitalized cancer patients for whom the PCT performed interventions were analyzed. The average patient age was 61 years. Hepatobiliary and pancreatic cancer were the most common primary sites (20%) followed by blood (12%) and lung (11%). Pain management was the most frequent reason for PCT consultation (67%) and PCT activities (65%). Delirium was more likely to be treated by the PCT, but less likely to be listed as a reason for consultation. The need for support for family and for decision making was less often recognized by hospital staff. Cancer-related fatigue (CRF) and depression were more likely listed as reasons for consultation, but less likely to receive PCT intervention. CONCLUSIONS: Delirium and the need for family and decision-making support were underrecognized by hospital staff. PCT intervention for CRF and depression was often withheld because of very late referral. Appropriate timing of PCT consultations is important. Providing educational opportunities for hospital staff to comprehensively assess patient's multidimensional distress is needed.

[A search for the risk factors for hiccups and evaluation of antiemetic therapy in CDDP-based chemotherapy, using cluster analysis].

Hiccups are often observed in patients treated with cisplatin(CDDP)-based chemotherapy. It has been reported that gender and specific dosages of CDDP and antiemetic drugs(e.g., dexamethasone and 5-HT3 receptor antagonist)using standard therapy are major risk factors in the onset of hiccups. Recently, aprepitant has been added to the antiemetic therapy in CDDP-based chemotherapy. However, it is not known how the onset of hiccups takes place in antiemetic therapy including aprepitant according to the guideline. In this study, we used cluster analysis to classify 229 patients treated with CDDP-based chemotherapy, to investigate the effect of antiemetic therapy on the onset of hiccups and chemotherapy-induced nausea and vomiting(CINV). Our analysis indicated that aprepitant was not a major risk factor for the onset of hiccups in the high CDDP dose group(≥70 mg/m(2)). However, an effect of antiemesis was confirmed in the standard therapy with aprepitant. In conclusion, we suggest that aprepitant is effective for CINV, without causing the onset of hiccups in patients treated with high-dose CDDP-based chemotherapy.

[A survey of the dosage of zoledronic acid and investigation of the relationship between renal function and adverse events].

Zoledronic acid(ZA)dosage should be adjusted according to the risk it poses for renal impairment. The recommended dosage for patients with creatinine clearance(Ccr)of less than 60mL/min was established on the basis of an area under the curve analysis, but is doubted because it was calculated without performing a clinical trial. Creatinine secretion from the renal tubule affects Ccr; therefore, using Ccr as the basis for dosage adjustment may be inappropriate since this can cause an overestimation of the glomerular filtration rate(GFR). The Japanese Society of Nephrology recommends using the estimated GFR(eGFR)for evaluating renal function. Therefore, this study investigated the relationship between renal function before and adverse events(AEs)after ZA administration. The dosage of only 3 of the 47 patients with Ccr less than 60mL/min could be adjusted on the basis of Ccr. During ZA therapy(3 courses), the blood urea nitrogen level and occurrence of hypokalemia were higher in the non-adjusted group than in the adjusted group, but the total number of AEs was equivalent for both groups. For all the patients, Ccr and eGFR were used as parameters for investigating AEs; the total number of AEs was equivalent for patients with differing levels of renal function. Therefore, we suggest that AEs observed during ZA therapy did not depend on the renal function level before ZA administration.

Characteristics for enhanced response of serotonin-evoked ion dynamics in differentiated NG108-15 cells.

Characteristics for the up-regulated response in the concentration of intracellular calcium ion ([Ca(2+)]( i )) and in the sodium ion (Na(+)) current by serotonin (5-HT) were investigated in differentiated neuroblastoma x glioma hybrid NG108-15 (NG) cells. The results for the changes in [Ca(2+)]( i ) by 5-HT were as follows, (1) The 5-HT-induced Ca(2+) response was inhibited by 3 x 10(-9) M tropisetron (a 5-HT(3) receptor blocker), but not by other types of 5-HT receptor blockers; (2) The 5-HT-induced Ca(2+) response was mainly inhibited by calciseptine (a L-type Ca(2+) blocker), but not by other types of Ca(2+) channel blockers or 10(-7) M TTX (a voltage-sensitive Na(+) channel blocker); (3) When the extracellular Na(+) was removed by exchange with choline chloride or N-methyl-D-glucamine, the 5-HT-induced Ca(2+) response was extremely inhibited. The results for the 5-HT-induced Na(+) current by the whole cell patch-clamp technique were as follows, (1) The 5-HT-induced Na(+) current in differentiated cells was significantly larger than that in undifferentiated cells; (2) The ED(50) value for 5-HT-induced Na(+) current in undifferentiated and differentiated cells was almost the same, about 4 x 10(-6) M each other; (3) The 5-HT-induced Na(+) current was completely blocked by 3 x 10(-9) M tropisetron, but not by other 5-HT receptor antagonists and 10(-7) M TTX. These results suggested that 5-HT-induced Ca(2+) response in differentiated NG cells was mainly due to L-type voltage-gated Ca(2+) channels allowing extracellular Na(+) to enter via 5-HT(3) receptors, but not through voltage-gated Na(+) channels.

Enhancement of sodium current in NG108-15 cells during neural differentiation is mainly due to an increase in NaV1.7 expression.

It is well known that morphological and functional changes during neural differentiation sometimes accompany the expression of various voltage-gated ion channels. In this work, we investigated whether the enhancement of sodium current in differentiated neuroblastoma x glioma NG108-15 cells treated with dibutyryl cAMP is related to the expression of voltage-gated sodium channels. The results were as follows. (1) Sodium current density on peak voltage in differentiated cells was significantly enhanced compared with that in undifferentiated cells, as detected by the whole-cell patch clamp method. The steady-state inactivation curve in differentiated cells was similar to that for undifferentiated cells, but a hyperpolarized shift in the activation curve for differentiated cells was observed. The sodium currents of differentiated and undifferentiated cells were completely inhibited by 10(-7) M tetrodotoxin (TTX). (2) The only Na(V) mRNA with an increased expression level during neuronal differentiation was that for NaV1.7, as observed by real-time PCR analysis. (3) The increase in the level of NaV1.7 alpha subunit expression during neuronal differentiation was also observed by immunocytochemistry; in particular, the localization of NaV1.7 alpha subunits on the soma, varicosities and growth cone was significant. These results suggest that the enhancement of TTX-sensitive sodium current density in differentiated NG108-15 cells is mainly due to the increase in the expression of the TTX-sensitive voltage-gated Na+ channel, NaV1.7.

Enhancement of serotonin- and bradykinin-evoked calcium ion dynamics in differentiated NG108-15 cells.

Dynamic changes in the concentration of intracellular free-calcium ion ([Ca(2+)](i)) by carbachol (CCh) and neurotransmitter candidates was investigated in undifferentiated and differentiated neuroblastomaxglioma hybrid NG108-15 (NG) cells. [Ca(2+)](i) was increased in a dose-dependent manner by bradykinin (BK) and serotonin (5-HT) in differentiated NG cells, and the response to BK and 5-HT was significantly greater than that in undifferentiated NG cells. The EC(50) value of BK was approximately 1.5 x 10(-8)M in both undifferentiated and differentiated NG cells. The EC(50) value of 5-HT in differentiated NG cells was about 5 x 10(-6)M. The response to BK and 5-HT was almost completely inhibited by 10 nM Hoe140 (a BK B2 receptor antagonist) and 3 nM tropisetron (a 5-HT(3) receptor antagonist), respectively. These results suggest that there are some mechanisms by which the response evoked by BK and 5-HT is up-regulated in differentiated NG cells.

Enhancement of veratridine-induced sodium dynamics in NG108-15 cells during differentiation.

Developmental changes in dynamics of Na+ were studied in neuroblastomaxglioma hybrid NG108-15 cells during differentiation which was induced by dibutyryl cAMP (Bt2cAMP). Ratiometric Na+ imaging with a Na+-sensitive fluorescent dye SBFI (sodium-binding benzofuran isophthalate) revealed that the intracellular Na+ concentration ([Na+]i) was not affected by the application of high K+ (60 mM) solution to either control or differentiated cells. When cells were exposed to 50 microM veratridine (Vtd), an agonist of voltage-sensitive sodium channels (VSSCs), a significant increase in [Na+]i was observed in differentiated but not in undifferentiated cells. Calculated mean [Na+]i value increased from the basal 10.4 to 44.1 mM in response to 50 microM Vtd. This Vtd response was reversibly inhibited by tetrodotoxin (TTX), a specific blocker for VSSCs, in a dose-dependent manner (IC50 = 1 nM). It is suggested that VSSCs in NG108-15 cells are sensitive to TTX and Vtd and that the number of VSSCs increases during differentiation.

Increased response to high KCl-induced elevation in the intracellular-Ca(2+) concentration in differentiated NG108-15 cell and the inhibitory effect of the L-type Ca(2+) channel blocker, calciseptine.

Characteristics of the increasing effect for the concentration of intracellular calcium ions ([Ca(2+)](i)) by high-KCl application were investigated in the neuroblastomaxglioma hybrid NG108-15 cell line (NG108-15 cells). The present study confirmed that the increasing effect of [Ca(2+)](i) by high-KCl application in single NG108-15 cells, differentiated with dibutyryl cAMP (Bt(2)cAMP), was significantly enhanced, compared to undifferentiated cells. The following observations were made at first: (1) The response to high-KCl application, in both undifferentiated and differentiated cells, was significantly inhibited by calciseptine (CaS), an L-type Ca(2+) channel blocker, but not by N-, P- and R-type Ca(2+) channel blockers. The IC(50) values for CaS in both undifferentiated and differentiated cell was almost identical. (2) The inhibitory effect of CaS was irreversible. (3) The increasing effect for [Ca(2+)](i) by high-KCl application was completely dependent on the presence of extracellular calcium ions. (4) The increased [Ca(2+)](i) by high-KCl application under a plateau concentration was quickly decreased to basal levels when the high-KCl solution was exchanged for a high-KCl solution containing EGTA (without CaCl(2)). Together, these results suggest that the enhancement of the response effect of [Ca(2+)](i) by high-KCl application in differentiated single NG108-15 cells was mainly due to the quantitative increase of L-type voltage-sensitive calcium channels (VSCCs), which were irreversibly inhibited by CaS.

Effects of calmodulin and Ca2+ channel blockers on omega-conotoxin GVIA binding to crude membranes from alpha1B subunit (Cav2.2) expressed BHK cells and mice brain lacking the alpha1B subunits.

Characteristics for the specific binding of 125I-omega-CTX GVIA and 125I-omega-CTX MVIIC to crude membranes from BHKN101 cells expressing the alpha1B subunits of Cav2.2 channels and from mice brain lacking the alpha1B subunits of Cav2.2 channels, particularly, the effects of CaM and various Ca2+ channel blockers on these specific bindings were investigated. Specific binding of 125I-omega-CTX GVIA to the crude membranes from BHKN101 cells was observed, but not from control BHK6 cells. omega-CTX GVIA, omega-CTX MVIIC and omega-CTX SVIB inhibited the specific binding of 125I-omega-CTX GVIA to crude membranes from BHKN101 cells, and the IC50 values for omega-CTXGVIA, omega-CTX MVIIC and omega-CTX SVIB were 0.07, 8.5 and 1.7 nM, respectively. However, omega-agatoxin IVA and calciseptine at concentrations of 10(-9)-10(-6) M did not inhibit specific binding. Specific binding was also about 80% inhibited by 20 microg protein/ml CaM. The amount of 125I-omega-CTX GVIA (30 pM) specifically bound to membranes from brain of knockout mice lacking alpha1B subunits of Cav2.2 channels was about 30% of that to the crude membranes from brain of wild-type. On the other hand, specific binding of 125I-omega-CTX MVIIC (200 pM) was observed on the crude membranes of both BHKN101 and control BHK6 cells. The specific binding of 125I-omega-CTX MVIIC (200 pM) was not inhibited by omega-CTX GVIA and omega-CTX SVIB, and also omega-Aga IVA and calciseptine at concentrations of 10(-9)-10(-7) M, although specific binding was almost completely dose dependently inhibited by non-radiolabeled omega-CTX MVIIC (IC50 value was about 0.1 nM). 20 microg protein/ml CaM did not inhibit specific binding. Therefore, these results suggest that BHKN101 cells have a typical Cav2.2 channels which are also inhibited by CaM and have not specific binding sites for omega-CTX MVIIC, although omega-CTX MVIIC is a blocker for both Cav2.1 (alpha1A; P/Q-type) and Cav2.2 channels.