Self-assessment sheet submission rate predicts technique survival in patients initiating peritoneal dialysis.

AIM: Patients play a crucial role in preventing peritoneal dialysis (PD)-related events, including peritonitis and fluid overload, as PD procedures are mainly carried out at home. We asked patients to submit a PD self-assessment sheet at each outpatient visit in our daily clinical practice and evaluated its usefulness for outcomes in patients initiating PD. METHODS: This retrospective cohort study included patients who underwent PD catheter insertion between January 2008 and October 2018. The submission rate of a PD self-assessment sheet was calculated from medical records until PD cessation or study completion (October 2020). The association between the submission rate and technique survival was analysed. RESULTS: Among the 105 recruited patients (78 men, 60.4 ± 12.2 years), 44 discontinued PD and transferred to haemodialysis during the study period. The follow-up was 52.3 (28.7-79.3) months, and the median submission rate was 78%. The log-rank test showed that technique survival was significantly better in patients with a submission rate ≥ 78% than those with a submission rate <78% (p = .006). The submission rate remained significantly associated with less technique failure (hazard ratio 0.88 per 10%, p = .002) by the Cox regression analysis adjusted for age, sex, Charlson comorbidity index, estimated glomerular filtration rate and geriatric nutritional risk index. CONCLUSION: The submission rate of a PD self-assessment sheet is useful as a predictor of technique survival in patients initiating PD. Instruction that increases submission may improve technique survival in PD patients.

Adverse drug events affecting medication persistence with rivastigmine patch application.

PURPOSE: The rivastigmine transdermal patch, the only existing cholinesterase inhibitor available as a transdermal delivery system for treating Alzheimer's disease, has been reported to inhibit progression of cognitive impairment and impairment in activities of daily living, in addition to reducing care burden and improving adherence. However, application of the rivastigmine patch also frequently results in erythema, pruritus, contact dermatitis, and other cutaneous adverse events at the application site, making it difficult to increase the effective dose and continue treatment. Therefore, we conducted a survey to examine the manifestation of adverse events and medication persistence in patients who were prescribed the rivastigmine patch. PARTICIPANTS AND METHODS: Three hundred and twelve patients diagnosed with Alzheimer's disease between July 1, 2011 and March 31, 2015 at the Toki Medical Clinic and who were prescribed a rivastigmine patch at the Sasayuri Community Pharmacy were involved in the study. Outcomes such as manifestation of adverse events, dose at manifestation, and dose reduction as well as discontinuation were retrospectively examined through medication counseling records. RESULTS: Adverse drug events developed in 209 of the 312 patients (67.0%). Approximately 70% of patients who developed adverse events did so before reaching the maintenance dose of 18 mg. The main adverse drug events were cutaneous reactions at the application site such as rash and erythema in 186 patients (59.6%) and gastrointestinal disorders such as nausea, vomiting, and diarrhea in 29 patients (9.3%). Also, of the 312 patients, 118 patients (37.8%) discontinued the rivastigmine patch; reasons for discontinuation included cutaneous application site reactions in 74 patients (62.7%), gastrointestinal disorders in 5 patients (4.2%), and psychiatric disorders in 6 patients (5.1%). Among the 74 patients who discontinued the rivastigmine patch due to application site disorders, the dose at the time of discontinuation was 4.5 mg in 22 patients (29.7%), 9 mg in 37 patients (50.0%), 13.5 mg in 10 patients (13.5%), and 18 mg in 5 patients (6.8%). CONCLUSION: Approximately 60% of patients who used the rivastigmine patch developed application site reactions, suggesting difficulty in increasing the dose to the effective dose and in continuing application. Also, ~80% of the patients who discontinued the rivastigmine patch due to application site reactions developed these reactions when the dose was increased to 9 mg.

Effect of continuous intravenous oxycodone infusion in opioid-naïve cancer patients with dyspnea.

AIM: Dyspnea is among symptoms that decrease quality of life for terminal cancer patients. There are few reports of the positive effects of oxycodone for the treatment of dyspnea, and no studies have focused on opioid-naïve patients. This study aimed to determine the efficacy and safety of continuous intravenous oxycodone infusion for opioid-naïve cancer patients with dyspnea. METHODS: Eligible patients were opioid-naïve cancer inpatients who received continuous oxycodone infusion as a treatment for dyspnea under the care of the palliative care team at Komaki City Hospital between November 2013 and December 2016. We retrospectively investigated the improvement of dyspnea following continuous oxycodone infusion from the medical records. RESULTS: This study included 19 patients, and the response rate to oxycodone infusion for dyspnea was 68.4%. Most participants were terminal cancer patients with performance status 3 or 4. Median survival of participants following continuous oxycodone infusion was 6 (range 1-377) days. No serious adverse events such as respiratory depression or somnolence were noted. CONCLUSION: Continuous oxycodone infusion could be a reasonable treatment option in the management of dyspnea in opioid-naïve cancer patients.

A case of successful concomitant administration of warfarin and uracil-tegafur/leucovorin achieved by self-measurement of INR.

A woman in her seventies who was started on warfarin after heart valve replacement began outpatient adjuvant chemotherapy with tegafur-uracil/leucovorin for rectal cancer. The patient performed weekly INR self-measurements at a health insurance pharmacy between outpatient visits. Results recorded in her personal medicine notebook were shared between her physician, a hospital pharmacist, and a pharmacy pharmacist. When INR values were outside the therapeutic target range, doses were altered according to the physician's instruction. Our approach enables the fine adjustment of warfarin doses according to changes in INR and contributes to the maintenance of the therapeutic target range and safe and appropriate outpatient chemotherapy.

"High-precision, reconstructed 3D model" of skull scanned by conebeam CT: Reproducibility verified using CAD/CAM data.

Computed tomography (CT) scanning has recently been introduced into forensic medicine and dentistry. However, the presence of metal restorations in the dentition can adversely affect the quality of three-dimensional reconstruction from CT scans. In this study, we aimed to evaluate the reproducibility of a "high-precision, reconstructed 3D model" obtained from a conebeam CT scan of dentition, a method that might be particularly helpful in forensic medicine. We took conebeam CT and helical CT images of three dry skulls marked with 47 measuring points; reconstructed three-dimensional images; and measured the distances between the points in the 3D images with a computer-aided design/computer-aided manufacturing (CAD/CAM) marker. We found that in comparison with the helical CT, conebeam CT is capable of reproducing measurements closer to those obtained from the actual samples. In conclusion, our study indicated that the image-reproduction from a conebeam CT scan was more accurate than that from a helical CT scan. Furthermore, the "high-precision reconstructed 3D model" facilitates reliable visualization of full-sized oral and maxillofacial regions in both helical and conebeam CT scans.

A Successful Case of a Patient Undergoing Warfarin and S-1 Therapy Using Internet-based Control of Home-measured PT-INR.

  To avoid major bleeding events in warfarin and S-1 combination therapy, PT-INR levels should be monitored frequently to allow for precise adjustments of the warfarin dose and to verify any side effects reported by the patient. We therefore developed a support system where outpatients obtain a home-measured PT-INR value using the CoaguChek(®) system and submit it along with details of any side effects to us via the Internet using their mobile phone. A 59-year-old man was started on warfarin (1.5 mg/d) and S-1 (100 mg/d), a combination preparation of tegafur, gimeracil, and oteracil potassium, to treat cholangiocarcinoma. The patient sent his data to the hospital pharmacist every two days after starting S-1 therapy. When the PT-INR was outside the target range of 1.5-2.7, the pharmacist, after consulting the physician, instructed the patient to change his warfarin dose by 0.5 mg. On day 24 after starting S-1, PT-INR had increased from 1.6 to 2.8, so the dose was decreased by 0.5 mg. Thereafter, the dose was adjusted by 0.5-1.0 mg during the observation period so that the patient was able to maintain the therapeutic range approximately 90% of the time. We anticipate this system can be applied to S-1 which interact with warfarin, thereby enabling safer anticoagulation therapy.

Acquisition of doxorubicin resistance facilitates migrating and invasive potentials of gastric cancer MKN45 cells through up-regulating aldo-keto reductase 1B10.

Continuous exposure to doxorubicin (DOX) accelerates hyposensitivity to the drug-elicited lethality of gastric cells, with increased risks of the recurrence and serious cardiovascular side effects. However, the detailed mechanisms underlying the reduction of DOX sensitivity remain unclear. In this study, we generated a DOX-resistant variant upon continuously treating human gastric cancer MKN45 cells with incremental concentrations of the drug, and investigated whether the gain of DOX resistance influences gene expression of four aldo-keto reductases (AKRs: 1B10, 1C1, 1C2 and 1C3). RT-PCR analysis revealed that among the enzymes AKR1B10 is most highly up-regulated during the chemoresistance induction. The up-regulation of AKR1B10 was confirmed by analyses of Western blotting and enzyme activity. The DOX sensitivity of MKN45 cells was reduced and elevated by overexpression and inhibition of AKR1B10, respectively. Compared to the parental MKN45 cells, the DOX-resistant cells had higher migrating and invasive abilities, which were significantly suppressed by addition of AKR1B10 inhibitors. Zymographic and real-time PCR analyses also revealed significant increases in secretion and expression of matrix metalloproteinase (MMP) 2 associated with DOX resistance. Moreover, the overexpression of AKR1B10 in the parental cells remarkably facilitated malignant progression (elevation of migrating and invasive potentials) and MMP2 secretion, which were lowered by the AKR1B10 inhibitors. These results suggest that AKR1B10 is a DOX-resistance gene in the gastric cancer cells, and is responsible for elevating the migrating and invasive potentials of the cells through induction of MMP2.

Effects on caregiver burden of a donepezil hydrochloride dosage increase to 10 mg/day in patients with Alzheimer's disease.

BACKGROUND: In this study, we evaluated changes in functioning and caregiver burden in Alzheimer's disease (AD) patients after a dosage increase that was made based on pharmacists' evaluation of AD patients' behavior in daily life. METHODS: Pharmacists used a checklist, a questionnaire, and the Repetitive Saliva Swallowing Test (RSST) to gather data on the daily life of AD patients taking donepezil 5 mg/day and their caregivers. In 27 cases, pharmacists suggested a dosage change to 10 mg/day to AD patients' physicians. Pharmacists then evaluated these patients for 16 weeks after the increase to determine changes in functional assessment staging, caregiver burden, and swallowing function. RESULTS: During the 16-week study, 20 of the 27 patients showed at least one-stage improvement in relation to the five assessed aspects of daily life (time/place, speech, bathing, dressing, and toileting). The mean score for caregiver burden due to personal strain was significantly lower after the dosage increase than before (5.15±3.76 at baseline; from 3.89±3.42 at week 4 to 3.59±3.90 at week 16; P<0.05), as was the mean score due to role strain (2.19±2.80 at baseline; 1.56±2.64 at week 8; P<0.05). After the dosage increase, the impaired swallowing function that accompanies AD was improved in the patients with swallowing problems, as indicated by a higher mean RSST score (1.22±0.67 at baseline; from 2.78±1.72 at week 4 to 2.78±1.79 at week 16; P<0.05). CONCLUSION: The dosage increase not only decreased caregiver burden, but also appeared to improve impaired swallowing function. Medication therapy management by pharmacists of AD patients, including the use of a checklist, contributed to the correct use of donepezil and improved quality of life for caregivers.

Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10.

Inhalation of 9,10-phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust, exerts fatal damage against a variety of cells involved in respiratory function. Here, we show that treatment with high concentrations of 9,10-PQ evokes apoptosis of lung cancer A549 cells through production of reactive oxygen species (ROS). In contrast, 9,10-PQ at its concentrations of 2 and 5 µM elevated the potentials for proliferation, invasion, metastasis and tumorigenesis, all of which were almost completely inhibited by addition of an antioxidant N-acetyl-l-cysteine, inferring a crucial role of ROS in the overgrowth and malignant progression of lung cancer cells. Comparison of mRNA expression levels of six aldo-keto reductases (AKRs) in the 9,10-PQ-treated cells advocated up-regulation of AKR1B10 as a major cause contributing to the lung cancer malignancy. In support of this, the elevation of invasive, metastatic and tumorigenic activities in the 9,10-PQ-treated cells was significantly abolished by the addition of a selective AKR1B10 inhibitor oleanolic acid. Intriguingly, zymographic and real-time PCR analyses revealed remarkable increases in secretion and expression, respectively, of matrix metalloproteinase 2 during the 9,10-PQ treatment, and suggested that the AKR1B10 up-regulation and resultant activation of mitogen-activated protein kinase cascade are predominant mechanisms underlying the metalloproteinase induction. In addition, HPLC analysis and cytochrome c reduction assay in in vitro 9,10-PQ reduction by AKR1B10 demonstrated that the enzyme catalyzes redox-cycling of this quinone, by which ROS are produced. Collectively, these results suggest that AKR1B10 is a key regulator involved in overgrowth and malignant progression of the lung cancer cells through ROS production due to 9,10-PQ redox-cycling.

[The investigation of understanding and comfort of patients taking Divigel(®) 1 mg].

Hormone replacement therapy (HRT) given by injection or administered orally or topically can improve the QOL of patients with menopausal symptoms. Because patient comfort is influenced largely by the dosage form, pharmacists should understand the properties of each dosage form and provide appropriate information to individual patients. In this study, we investigated the understanding of medicines and diseases of patients receiving HRT and discuss the approaches pharmacists can take to improve patients' adherence. Thirty-seven patients (mean age 51.7±3.6 years) taking estradiol gel (Divigel(®) 1 mg) completed a questionnaire asked by their pharmacist. Responses indicated 70% of patients failed to use the gel as prescribed, and they had poor knowledge of both the sites where the gel shouldn't be applied and appropriate measures to take if having forgotten to apply the gel (43% and 11% correct understanding, respectively). Since the duration of HRT treatment for menopausal symptom is 2-5 years, patients should be administered the minimum effective dose in the shortest amount of time. Hence it is important to maintain patients' adherence particularly in this limited administration period. HRT guidelines define HRT outcome as not only improvement of menopausal symptoms but also suppression of bone resorption, improvement of glucose and lipid metabolism, and reduced prevalence of Alzheimer's disease. Accordingly, pharmacists should facilitate proper adherence to HRT to improve and maintain women's QOL in the perimenopausal period, necessitating they actively provide pharmaceutical care such as preparing useful instructions patients can repeatedly use and periodically checking patients' understanding of their HRT medications.

[Evaluation of cognitive-behavioral therapy for drinking. Outcome of Japanese alcoholic patients].

This study examined the efficacy of a group-based cognitive-behavioral treatment (CBT) for Japanese alcoholic outpatients. Participants (N = 169) were assigned either to a CBT-based relapse prevention group or a TAU (treatment as usual) group. The CBT group received 12-session CBT treatment with a structured treatment workbook once a week. The TAU group received usual daycare treatment including 12-step meeting, vocational training and leisure activities. Participants in the CBT group demonstrated a significantly low relapse rate at the end of treatment. Moreover, coping skills of the CBT group participants were significantly improved than those of the TAU group at the 6-month follow-up period. However, at the 6-month follow-up, the difference in relapse rates diminished. The effectiveness of CBT for alcoholics was well documented in Western countries but few studies were conducted outside of the West. The results provide support for the use of CBT for Japanese alcoholics.

Inhibition of human aldose reductase-like protein (AKR1B10) by α- and γ-mangostins, major components of pericarps of mangosteen.

A human member of the aldo-keto reductase (AKR) superfamily, AKR1B10, was recently identified as both diagnostic marker and therapeutic target in the treatment of several types of cancer. In this study, we have examined AKR1B10 inhibition by five xanthone derivatives, components of pericarps of mangosteen, of which α- and γ-mangostins show potential anti-cancer properties. Among the five xanthones, γ-mangostin was found to be the most potent competitive inhibitor (inhibition constant, 5.6 nM), but its 7-methoxy derivative, α-mangostin, was the second potent inhibitor (inhibition constant, 80 nM). Molecular docking of the two mangostins in AKR1B10 and site-directed mutagenesis of the putative binding residues revealed that Phe123, Trp220, Val301 and Gln303 are important for the tight binding of γ-mangostin, and suggested that the 7-methoxy group of α-mangostin impairs the inhibitory potency by altering the orientation of the inhibitor molecule in the substrate-binding site of the enzyme.

Pharmacist-based Donepezil Outpatient Consultation Service to improve medication persistence.

AIM: Donepezil is widely used to delay the progression of cognitive dysfunction in patients with Alzheimer's disease (AD), but the efficacy of pharmacotherapy is often reduced by poor adherence to medication. In order to improve adherence by providing information about AD and the significance of pharmacotherapy, the Donepezil Outpatient Consultation Service (DOCS) was set up. The influence of this service on medication persistence was assessed in the present study. METHODS: Among outpatients starting donepezil therapy, we enrolled 59 patients between April 2008 and September 2010 before establishment of the DOCS (non-DOCS group) and 52 patients between October 2010 and March 2012 who attended the DOCS (DOCS group). Each patient's and their caregiver's understanding about the clinical features of AD and pharmacotherapy with donepezil were also assessed. Their understanding was compared before and after the DOCS, and the 1-year medication persistence rate and the reasons for discontinuation were also investigated. RESULTS: The 1-year medication persistence rate was significantly higher in the DOCS group than in the non-DOCS group (73.1% vs 49.2%, P = 0.008). We examined the association of medication persistence with age, sex, clinical dementia rating, living alone, and attending the DOCS. As a result, medication persistence was significantly higher in patients attending the DOCS. The main reasons for discontinuation of donepezil were transfer elsewhere (11) and gastrointestinal side effects (5) in the non-DOCS group, and transfer (9) and gastrointestinal side effects (3) in the DOCS group. The overall score for understanding was 2.5 ± 1.7 before attending the DOCS and it increased significantly to 5.7 ± 0.7 afterward (P < 0.001). CONCLUSION: The DOCS consultation provided by hospital pharmacists for AD patients and their caregivers improved understanding about the clinical features of dementia and provided pharmacological knowledge about antidementia drugs, leading to better adherence to pharmacotherapy that could maximize its effect.

Reduction of cytotoxic p-quinone metabolites of tert-butylhydroquinone by human aldo-keto reductase (AKR) 1B10.

2-tert-Butylhydroquinone (BHQ), an antioxidant used as a food additive, exhibits an anticancer effect, whereas it is carcinogenic in rodents at high doses. BHQ is metabolized into cytotoxic tert-butylquinone (BQ), which is further converted to 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one (TBEH) through 6-tert-butyl-2,3-epoxy-4-benzoquinone (TBE), which induces chromosomal aberration. The reductases for BQ and TBE may be protective against the toxicity of the two p-quinones, but the responsible human enzymes remain unidentified. In this study, we compared the ability of 12 human recombinant enzymes in the aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase superfamilies to reduce BQ and TBE. Among them, AKR1B10 was the most efficient catalyst of the stoichiometric two-electron reduction of BQ and TBE into BHQ and TBEH, respectively. BQ and TBE are more cytotoxic towards endothelial cells than BHQ and TBEH, and their cytotoxicity was decreased by the overexpression of AKR1B10 in the cells. Additionally, AKR1B10 gene expression in human HCT116 cells was up-regulated by treatments with BHQ, BQ and TBE. These results suggest a role for the enzyme in protection at least against the toxicity of the two p-quinone metabolites of BHQ.

Design, synthesis and evaluation of caffeic acid phenethyl ester-based inhibitors targeting a selectivity pocket in the active site of human aldo-keto reductase 1B10.

Inhibitors of a human aldo-keto reductase, AKR1B10, are regarded as promising therapeutics for the treatment of cancer, but those with both high potency and selectivity compared to the structurally similar aldose reductase (AKR1B1) have not been reported. In this study, we have found that, among honeybee propolis products, caffeic acid phenethyl ester (CAPE) inhibited AKR1B10 (IC(50) = 80 nM) with 7-fold selectivity over AKR1B1. Based on a model of docked CAPE in AKR1B10, its derivatives were designed, synthesized and evaluated for inhibitory potency. Among them, 3-(4-hydroxy-2-methoxyphenyl)acrylic acid 3-(3-hydroxyphenyl)propyl ester (10c) was the most potent competitive inhibitor (K(i) = 2.6 nM) with 790-fold selectivity for AKR1B10 over AKR1B1. Molecular docking of 10c and site-directed mutagenesis of AKR1B10 residues suggested that the interactions between the 2-methoxy and 3-hydroxy groups of 10c and the enzyme's Val301 and Gln114, respectively, are important for the inhibitor's selectivity. Additionally, the sub-µM concentration of 10c significantly suppressed the farnesal metabolism and cellular proliferation in AKR1B10-overexpressing cells.

Effects of open-air temperature on air temperature inside biological safety cabinet.

OBJECTIVE: In Japan, biological safety cabinets (BSCs) are normally used by medical staff while handling antineoplastic agents. We have also set up a class II B2 BSC at the Division of Chemotherapy for Outpatients. The air temperature inside this BSC, however, decreases in winter. We assumed that this decrease is caused by the intake of open-air. Therefore, we investigated the effects of low open-air temperature on the BSC temperature and the time of admixtures of antineoplastic agents. METHODS: The studies were conducted from January 1 to March 31, 2008. The outdoor air temperature was measured in the shade near the intake nozzle of the BSC and was compared with the BSC temperature. The correlation between the outdoor air temperature and the BSC temperature, the dissolution time of cyclophosphamide (CPA) and gemcitabine (GEM), and accurate weight measurement of epirubicin (EPI) solution were investigated for low and normal BSC temperatures. RESULT: The BSC temperature was correlated with the open-air temperature for open-air temperatures of 5-20°C (p < 0.0001). The dissolution of CPA and GEM at these temperatures was significantly delayed as compared to that at 25°C (p < 0.01 and p < 0.0001, respectively). The weight measurement of EPI solution using a syringe method lacks accuracy because of its high coefficient of viscosity at low temperatures (p < 0.01). CONCLUSION: These results suggest that the BSC temperature decreases below room temperature in winter when air is drawn from outdoors. We showed that the BSC temperature affects the dissolution rate of antineoplastic agents. Further, we suggested that the BSC temperature drop might delay the affair of the admixtures of antineoplastic agents and increase the waiting time of outpatients for chemotherapy.

[Incidence of taste disorder associated with cancer patients undergoing chemotherapy on an ambulatory basis].

Taste disorders are a common complaint among cancer patients undergoing chemotherapy on an ambulatory basis. We conducted a survey on the incidence of such disorders among 74 patients, and 45.95% (34 of 74 patients) developed taste disorders. When stratified by medication into a regimen including 5-FU and one including taxanes, taste disorders were found in 59.0% (23 of 39 patients) of the former and 60.0% (9 of 15) of the latter. The survey also included the effects of taste disorders on patients appetites. Both regimens led to reduced appetite in a number of these patients (39.1% and 44.4%, respectively). Among patients on the 5-FU-containing regimen, the FOLFOX/FOLFIRI therapy was found to be responsible for loss of appetite. Regarding change in tastes, many patients stated that the medication dulled their taste sensation except for bitterness; their capacity to sense intensity of taste remained unchanged. It was found that acute taste disorders develop frequently among patients on a high dosage of 5-FU or a taxane-containing regimen.

[An appropriate opioid rotation method for treatment of cancer pain--nationwide usage survey of opioid analgesics].

The use of opioid for treatment of cancer pain has become common with the spread of the WHO method for relief of cancer pain. However, it cannot yet be said whether such usage is appropriate. To understand how opioid analgesics are actually used, we conducted a nationwide mail-based questionnaire survey of doctors dealing with cancer pain treatment. Results indicate that at opioid rotation to fentanyl patch due to insufficient effect, the second opioid is used in a potency equianalgesic or less of the first, so the efficacy of the second is often insufficient. In cases where previous medication had an insufficient effect, taking rescue doses into account, we believe it is important to rotate opioid at 30- 50% above the equianalgesic dose.

[Development of taste disorders following FOLFOX-FOLFIRI therapy and its effects on the QOL of patients with colorectal cancer].

Taste disorders are frequent occurrences among those patients under the FOLFOX-FOLFIRI regimen for colorectal cancer. We conducted a study on the development of taste disorders among colorectal cancer patients under this regimen and the effect of such disorders on their QOL. Taste disorders occurred in 58.1%(18/31 cases)of these patients and the disorders affected appetites in 50%(9 cases). The changes in taste sensations were subtle in most but some described certain tastes as exaggerated. Others reported changes in all taste sensations, including sweet, salty, bitter and sour, as well as deliciousness. When tested via the QOL Survey Sheet(Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs: QOL-ACD), the QOL was found to have deteriorated significantly in those who stated that taste disorders affected their appetite, in comparison with those who were unaffected. In patients with colorectal cancers and treated with the FOLFOX-FOLFIRI regimen, taste disorders are frequent occurrences. The poor nutritional state due to a loss of appetite may constitute a factor responsible for a lowering QOL.

[Prevention of oxaliplatin-related neurotoxicity by glutathione infusions].

We have used glutathione for prevention of oxaliplatin-related neurotoxicity with reference to the article of Cascinu et al. We investigated oxaliplatin-related neurotoxicity in Kariya Toyota General Hospital(KTGH)and compared with the data described in the article of Gamelin about the severity of its neurotoxicity. Grade 3 neurotoxicity was observed in only 5 of 44 patients(11.4%). The median number of cycles and cumulative dose of oxaliplatin were 12 cycles(5-27 / cycles)and 802.2(273.2-1,952.4)mg/m(2), respectively, at Grade 3 neuropathy. We evaluated retrospectively neuro-toxicity grade at cumulative oxaliplatin doses of approximately 500-520 mg/m(2). The severity of neurotoxicity observed in KTGH was significantly lower than in the group without Ca/Mg. We found no difference between the group with glutathione and / with Ca/Mg. Glutathione infusions seemed to prevent oxaliplatin-related neurotoxicity.