The effect of an elemental diet on oral mucositis of esophageal cancer patients treated with DCF chemotherapy: a multi-center prospective feasibility study (EPOC study)

Purpose

Oral mucositis (OM) is one of the most uncomfortable adverse events experienced by cancer patients undergoing chemotherapy. Previous reports have revealed that the oral administration of an elemental diet (ED) may prevent OM. However, the incidence of OM has not been accurately determined by specialized diagnostic methods and the effects of an ED on OM remain unclear. We investigated the dose that could feasibly be administered and its effects with regard to the suppression of OM in esophageal cancer patients undergoing chemotherapy.

Methods

We performed a prospective multi-center feasibility study of the administration of an ED (160 g/day) with 2 cycles of docetaxel/cisplatin/5-FU (DCF) chemotherapy. We assessed compliance to the ED for 49 days and the incidence of OM according to the amount of the ED that was orally administered. The incidence of OM was graded by a dental specialist who was experienced in dental oncology using a central OM review system.

Results

Fourteen of 20 patients (70%) were able to complete the orally administered ED (160 g/day) during the course of chemotherapy. Three patients (15%) could not take the ED orally for 9, 14, and 21 days, respectively, while 1 patient (5%) took the ED orally at an average dose of 80 g/day for 35 days. The remaining 2 patients (10%) could not take the 80 g/day dose for 11 and 12 days, respectively. The incidence of grade?≥?2 OM in the ED completion group (15.4%, 2 of 13 patients) was significantly lower than that in the non-completion group (66.7%, 4 of 6 patients) (p?=?0.046).

Conclusions

An ED might be a one of the test treatment to reduce the incidence of OM in esophageal cancer patients treated with DCF and should be evaluated in further randomized study.

Clinical trial

The date of submission: Dec 08th, 2017.

     

Trends in Asthma Mortality in Japan

Asthma mortality has been increasing in many developed countries in recent years, so we have described the epidemiological features of asthma in Japan. Data on all certified asthma deaths from 1950 to 1997 were obtained from The National Vital Statistics, published annually by the Ministry of Health and Welfare. Trends in crude and age-adjusted asthma mortality rates, as well as age-specific mortality rates, were analyzed. Age and birth cohort effects on mortality rates were also examined using multiplicative models. Between 1950 and 1980, crude asthma mortality rates steadily decreased in both sexes and began to level off thereafter. Age-adjusted mortality rates have also decreased since 1950, and showed a persistent downward trend in both sexes even in recent years. Asthma mortality rates were higher in males than in females during the entire study period. When analysis was restricted to those aged 5 to 34 years, an upward trend since 1980 was observed. The multiplicative model showed a rapidly decreasing cohort effect on mortality among those born after 1860. However, the slope increased in the cohorts born after 1950 in both sexes. The age effect increased linearly with advancing age after 50 years in both sexes. Overall asthma mortality rates have been decreasing during the past five decades in Japan, but the mortality rate has increased among the 5-34-year-old age group since 1980. The high fatality rate stemming from the overuse of beta 2-agonists may account for the mortality increase.     

Accumulation of cholera toxin and GM1 ganglioside in the early endosome of Niemann–Pick C1-deficient cells

We investigated intracellular trafficking of GM1 ganglioside in Niemann-Pick C1 (NPC1)-deficient Chinese hamster ovary cells [NPC1(-) cells] by using cholera toxin (CT) as a probe. Both the holotoxin and the B subunit (CTB) accumulated in GM1-enriched intracellular vesicles of NPC1(-) cells. CTB-labeled vesicles contained the early endosome marker Rab5 but not lysosome-associated membrane protein 2 and were not labeled with either Texas red-transferrin or Lysotracker, indicating that they represent early endosomes. Similarly, CT accumulated in intracellular vesicles of human NPC fibroblasts that contained both Rab5 and early endosomal antigen 1. CTB accumulation in NPC1(-) cells was abolished by expression of wild-type NPC1 but not by mutant proteins with a mutation either in the NPC domain or the sterol-sensing domain. A part of these mutant NPC1 proteins expressed in NPC1(-) cells was localized on CTB-labeled vesicles. U18666A treatment of "knock in" cells [NPC1(-) cells that stably expressed wild-type NPC1] caused CTB accumulation similar to that in NPC1(-) cells, and a part of wild-type NPC1was localized on CTB-labeled vesicles in drug-treated cells. Finally, CT tracer experiments in NPC1(-) cells revealed retarded excretion of internalized toxin into the culture medium and an increase in the intracellular release of A subunits. In accordance with the latter result, CT was more effective in stimulating cAMP formation in NPC1(-) than in wild-type cells. These results suggest that transport of CT/GM1 complexes from the early endosome to the plasma membrane depends on the function of NPC1, whereas transport to the Golgi apparatus/endoplasmic reticulum does not.     

Unusual left ventricular dilatation without functional or biochemical impairment in normotensive extremely overweight Japanese professional sumo wrestlers

To explore the physiologic limit of left ventricular (LV) enlargement, we performed echocardiography and air displacement plethysmography to respectively assess LV dimension and function and the body composition of Japanese professional sumo wrestlers. After excluding subjects with cardiovascular disease, hypertension, plasma brain natriuretic peptide (BNP) > or =17.9 pg/ml, diabetes mellitus, or asthma, 331 subjects (mean +/- SD age, 21.6 +/- 3.7 years; height 179.2 +/- 5.3 cm; weight 1,17.9 +/- 21.5 kg; percent fat, 29.6 +/- 6.6%) were analyzed. LV end-diastolic dimension averaged 58.4 +/- 3.7 mm and was within the generally regarded normal limit (< or =54 mm) in 14.5% of subjects, but was > or =60 mm in 41.1% of subjects. LV septal and posterior wall thicknesses were 10.3 +/- 0.9 and 10.2 +/- 0.9 mm, respectively. Peak E- and A-wave velocities, E/A ratio, LV fractional shortening, and BNP were 96 +/- 16 and 51 +/- 13 cm/s, 2.0 +/- 0.7, 33.5 +/- 4.5%, and 3.1 +/- 3.7 pg/ml, respectively. LV end-diastolic dimension was not correlated with these indexes of LV function or with plasma BNP levels, but was significantly correlated with height, weight, body surface area, fat-free mass, and fat mass. These results show that among very large, highly trained, professional athletes, LV end-diastolic dimension frequently exceeds the traditionally accepted upper limit of normal for the general population. This increase in LV end-diastolic dimension may thus represent an extreme example of the physiologic adaptation of the athlete's heart.     

Diagnostic value of 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) in patients with chest pain. Comparison with rest-stress 99mTc-tetrofosmin SPECT and coronary angiography.

BACKGROUND: Basic and clinical studies have indicated that 15-(p-[(123)I] iodophenyl)-3-(R, S) methylpentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) can identify ischemic myocardium without evidence of myocardial infarction by the regional decline of tracer uptake. The present study compared BMIPP SPECT with rest-stress myocardial perfusion imaging (MPI) findings and coronary angiography (CAG) in 150 patients with acute chest pain. METHODS AND RESULTS: Patients with acute chest pain who underwent all of the following tests were selected: MPI at rest-stress, BMIPP SPECT at rest and CAG. Organic coronary artery stenosis (>or=75%) was observed in 46 patients, 27 patients had total or subtotal coronary occlusion by spasm in the spasm provocation test on CAG and the remaining 77 patients had no significant coronary artery stenosis or spasm. The sensitivity of BMIPP at rest to detect organic stenosis was significantly higher (54%) than that of rest-MPI (33%, p<0.005), but lower than that of stress-MPI (76%, p=0.05). The sensitivity of BMIPP at rest to detect spasm was significantly higher (63%) than that of both rest-MPI (15%; p<0.001) and stress-MPI (19%; p<0.001). Overall, the sensitivity of BMIPP at rest to detect both organic stenosis and spasm was significantly higher (58%) than that of rest-MPI (26%; p<0.001), despite having no significance with that of stress-MPI (55%). The specificity was not significantly different among the three imaging techniques. CONCLUSION: Resting BMIPP SPECT is an alternative method to stress MPI for identifying patients with not only organic stenosis but also spasm without the need for a stress examination.     

Neuronal cell death by Alzheimer's disease-relevant insults and its rescue

Neuronal cell death accounts for the clinical manifestations in Alzheimer's disease (AD). To establish the curative therapy of AD, neuroprotection is one of the primary therapeutic targets, and the elucidation of the mechanism of neuronal cell death is mandatory. Detailed characterization of neuronal cell death caused by familial AD (FAD)-linked mutant genes revealed that different cell death pathways are evoked by different types of mutants. Humanin (HN), a newly identified neuroprotective peptide, suppresses neuronal cell death caused by all known FAD mutants and A beta, while it has no effect on neuronal cell death caused by AD-irrelevant insults. The functional target of HN is the antagonism to neuronal death, not the modulation of A beta production, suggesting that HN-based medication can be combined with other remedies targeting A beta. HN is a promising seed for a novel therapy aiming at complete cure of AD through the suppression of neuronal loss.     

Tranilast inhibits the proliferation of uterine leiomyoma cells in vitro through G1 arrest associated with the induction of p21(waf1) and p53

Uterine leiomyoma is a mesenchymal tumor composed of smooth muscle cells with fibrous tissues and many mast cells. Tranilast is known to suppress fibrosis or to work as a mast cell stabilizer and is reported to inhibit proliferation of vascular smooth muscle cells. In this study, we examined the effects of tranilast on cultured human leiomyoma cells in vitro to evaluate whether this agent has the potential to inhibit the growth of uterine leiomyomas. Tranilast inhibited the proliferation of cultured leiomyoma cells in a dose-dependent manner without any cytotoxic effect or induction of apoptosis. In association with the inhibitory effect, tranilast induced the cyclin-dependent kinase (CDK) inhibitor p21(waf1) and tumor suppressor gene p53 and decreased CDK2 activity. These results suggest that tranilast arrests the proliferation of uterine leiomyoma cells at the G0/G1 phase, through the suppression of CDK2 activity via an induction of p21(waf1) and p53. Tranilast was concluded to be a potent agent to inhibit proliferative activity of uterine leiomyoma cells.     

Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis

Context: Allergy to hydrolyzed wheat protein in facial soap has become a major social issue in Japan. It has been reported that the most frequent early symptoms of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by long-term use.

Objective: We evaluated the relation between tear fluid levels of specific IgE for wheat and the features of allergic conjunctivitis.

Methods: A prospective, non-randomized, cross-sectional study was conducted in 103 patients with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and sex-matched healthy control subjects (control group). Specific IgE for wheat was measured in tear fluid with an immunochromatography assay, and a skin prick test (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and the total ocular symptom score for allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions associated with allergic conjunctivitis.

Results: The IgE positive rate and specific IgE score were both higher in the allergic group than in the control group (71.8% versus 40.0% and 1.9?±?0.7 versus 1.4?±?0.5). A positive SPT for wheat was also more frequent in the allergic group than in the control group (6.8% versus 0.0%). Within the allergic group, patients with a positive SPT had higher specific IgE scores than patients with a negative SPT (3.3?±?0.5 versus 1.8?±?0.6, p?r?=?0.665), tearing (r?=?0.672), and the total ocular symptom score (r?=?0.204). Wheat IgE in tear fluid was also correlated with the severity of rhinitis symptoms, including sneezing (r?=?0.610), nose blowing (r?=?0.640), and nasal obstruction (r?=?0.677). Furthermore, the tear fluid wheat IgE score was correlated with five objective features of allergic conjunctivitis (p?Conclusions: These results suggest that wheat allergy may be involved in the development of allergic conjunctivitis.