Medium-Term Effects of Insulin Degludec on Patients with Type?1 Diabetes Mellitus

Objective

The aim of this study was to analyze the changes in daily blood glucose fluctuation and insulin dose in patients with type 1 diabetes mellitus (T1DM) undergoing basal-bolus therapy following a switching of basal insulin used from insulin glargine or detemir to insulin degludec.

Methods

Seven patients with T1DM were enrolled. All patients treated with insulin glargine or detemir twice daily were switched to insulin degludec with 80–90 % of the prior insulin dose. During the study period, the basal insulin doses were adjusted by the attending physician. The patients underwent continuous glucose monitoring before, 3 days after, and 24 weeks after switching to insulin degludec. The daily insulin dose was analyzed before, 3 days after, and 24 weeks after switching. Glycated hemoglobin levels were measured before and 24 weeks after switching.

Results

The blood glucose profile did not change significantly before and after switching. On the other hand, the total daily insulin dose and total daily basal insulin dose decreased significantly 24 weeks after switching.

Discussion

In patients with T1DM undergoing insulin glargine or detemir treatment, it is possible to achieve similar glycemic control in the medium term with a once daily, lower dose of insulin degludec.     

Acute enhancement of non‐rapid eye movement sleep in rats after drinking water contaminated with cadmium chloride

Cadmium (Cd) is a heavy metal widely used or effused by industries. Serious environmental Cd pollution has been reported over the past two centuries, whereas the mechanisms underlying Cd‐mediated diseases are not fully understood. Interestingly, an increase in reactive oxygen species (ROS) after Cd exposure has been shown. Our group has demonstrated that sleep is triggered via accumulation of ROS during neuronal activities, and we thus hypothesize the involvement of Cd poisoning in sleep–wake irregularities. In the present study, we analyzed the effects of Cd intake (1–100 ppm CdCl₂ in drinking water) on rats by monitoring sleep encephalograms and locomotor activities. The results demonstrated that 100 ppm CdCl₂ administration for 28 h was sufficient to increase non‐rapid‐eye‐movement (non‐REM) sleep and reduce locomotor activities during the night (the rat active phase). In contrast, free‐running locomotor rhythms under constant dim red light and their re‐entrainment to 12:12‐h light/dark cycles were intact under chronic (1 month) 100 ppm CdCl₂ administrations, suggesting a limited influence on circadian clock movements at this dosage. The relative amount of oxidized glutathione increased in the brain after the 28‐h 100 ppm CdCl₂ administrations similar to the levels in cultured astrocytes receiving H₂O₂ or CdCl₂ in culture medium. Therefore, we propose Cd‐induced sleep as a consequence of oxidative stress. As oxidized glutathione is an endogenous sleep substance, we suggest that Cd rapidly induces sleepiness and influences activity performance by occupying intrinsic sleep‐inducing mechanisms. In conclusion, we propose increased non‐REM sleep during the active phase as an index of acute Cd exposure. Copyright © 2013 John Wiley & Sons, Ltd.     

Longitudinal clinical course of three Japanese patients with Leber congenital amaurosis/early-onset retinal dystrophy with RDH12 mutation

Purpose

To report the longitudinal clinical course of three Japanese patients from two families with Leber congenital amaurosis/early-onset retinal dystrophy (LCA/EORD), and the results of next-generation DNA sequences on them.

Patients and methods

The patients were three Japanese children: a 4-year-old girl, a 6-year-old boy, and a 3-year-old girl. Patients 1 and 2 were siblings, and patient 3 was from an unrelated family. Standard ophthalmic examinations including perimetry, electroretinography, optical coherence tomography, and ultrasonography were performed on each patient. The patients were observed for 28, 16, and 10 years. Whole exomes of the patients and their non-symptomatic parents were analyzed using a next-generation sequence technique.

Results

The decimal visual acuity varied between 0.07 and 0.6 at the initial visit and decreased to counting finger to hand motion in their teens. Funduscopy showed diffuse retinal and macular degeneration. During the follow-up period, a posterior staphyloma developed and the macular area became atrophic. Patient 1 developed cataracts in her early twenties. Genetic analysis revealed a homozygous A126V substitution in the RDH12 gene in all patients.

Conclusions

The three patients with LCA/EORD had a progressive decrease of their vision with the formation of a posterior staphyloma. This is the first report of Japanese patients with LCA/EORD with a RDH12 mutation.     

Exploring the perceived changes and the reasons why expected outcomes were not obtained in individual levels in a successful regional palliative care intervention trial: an analysis for interpretations

Context

The Japan Outreach Palliative Care Trial of Integrated Model (OPTIM) study, a mixed-methods study to evaluate the effects of a comprehensive regional palliative care program, revealed that the program provided broad positive outcomes at the regional level: increased home death, palliative care use, patient- and family-reported qualities of care, and health care professionals’ difficulties. Not all participants however obtained positive outcomes and thus exploring the reasons why expected outcomes were observed in individual levels could be of value.

Aims

The primary aims were to explore why expected outcomes were not obtained in individual participants, and the perceived changes in daily practices of physicians and nurses were explored.

Subjects and methods

Postintervention questionnaire survey on 857 patients, 1,137 bereaved family members, 706 physicians, and 2,236 nurses were analyzed.

Results

The reasons for not achieving home deaths included unexpected rapid deterioration, caregivers unavailable, concerns about adequate responses to sudden changes, and physical symptoms uncontrolled, while lack of physician availability at home and lack of information from physicians were less frequently reported. The reasons for not receiving specialized palliative care services were the lack of recommendations from physicians and no information about palliative care services. The reason for evaluating the quality of palliative care as not high was that clinicians tried to relieve symptoms, but there were limited effects and insufficient time. Many physicians and nurses reported that they became more aware of palliative care, that the availability of palliative care specialists and knowledge about palliative care improved, and that they cooperated with other regional health care providers more easily.

Conclusion

The OPTIM study seemed to succeed in optimizing physician availability at home, improves physician information about home care, achieved maximum efforts to relieve patient distress by clinicians, and increased communication among regional health care professionals. To achieve further better outcomes, multiple interventions to the health care system to be performed on the basis of a comprehensive regional palliative care program are proposed.     

Effect of orally administered Hochu-ekki-to,a Japanese herbal medicine,on contact hypersensitivity caused by repeated application of antigen

The effects of oral administration of Hochu-ekki-to (HET; bu-zhong-yi-qi-tang in Chinese), a traditional Japanese and Chinese herbal medicine, on chronic contact hypersensitivity were investigated. HET suppressed ear swelling due to chronic contact hypersensitivity caused by repeated application of 2,4,6-trinitro-1-chlorobenzene (TNCB). HET significantly suppressed not only increases in hapten-specific immunoglobulin E (IgE) and IgG1 titer due to repeated application of TNCB, but also total IgE and IgG1 concentration in the serum. Interleukin 4 (IL-4) level in inflamed ear tissue was significantly increased by repeated application of TNCB, and this increase in IL-4 level in the ear was significantly suppressed by oral administration of HET. Interferon gamma (IFN-gamma), IL-2, IL-5, IL-10 and IL-12 levels are not changed as much as IL4 by TNCB and HET did not alter these cytokines as much as IL-4. These results suggest that oral administration of HET suppresses chronic contact hypersensitivity, and it can be assumed that the suppression of serum Ig E and Ig G1 and IL-4 in inflamed ear.     

A case of pseudoaneurysm of the deep femoral artery successfully treated by NBCA embolization under occlusion

Transcatheter embolization of bleeding from distal branches of small arteries can be difficult. N-butyl cyanoacrylate (NBCA) was originally used as a tissue adhesive material, and recent evidence suggests that it can also be used as an embolic material. This report describes a case in which a pseudoaneurysm arising from the distal portion of a small branch of the deep femoral artery was successfully embolized with NBCA using a new technique with a microballoon catheter. Advantages of this technique include its safely, short treatment time, good control of the embolization range, absence of fragmentation, favorable polymerization dynamics, and absence of glue reflux or excessive distal spread of the glue.     

Letrozole ameliorates liver fibrosis through the inhibition of the CTGF pathway and 17β-hydroxysteroid dehydrogenase 13 expression

Journal of Gastroenterology - To establish a treatment option for liver fibrosis, the possibility of the drug repurposing theory was investigated, with a focus on the off-target effects of active...