Randomized controlled trial for assessment of Internet of Things system to guide intensive glucose control in diabetes outpatients: Nagoya Health Navigator Study protocol.

The Internet of Things (IoT) allows collecting vast amounts of health-relevant data such as daily activity, body weight (BW), and blood pressure (BP) automatically. The use of IoT devices to monitor diabetic patients has been studied, but could not evaluate IoT-dependent effects because health data were not measured in control groups. This multicenter, open-label, randomized, parallel group study will compare the impact of intensive health guidance using IoT and conventional medical guidance on glucose control. It will be conducted in outpatients with type 2 diabetes for a period of 6 months. IoT devices to measure amount of daily activity, BW, and BP will be provided to IoT group patients. Healthcare professionals (HCPs) will provide appropriate feedback according to the data. Non-IoT control, patients will be given measurement devices that do not have a feedback function. The primary outcome is glycated hemoglobin at 6 months. The study has already enrolled 101 patients, 50 in the IoT group and 51 in the non-IoT group, at the two participating outpatient clinics. The baseline characteristics of two groups did not differ, except for triglycerides. This will be the first randomized, controlled study to evaluate IoT-dependent effects of intensive feedback from HCPs. The results will validate a new method of health-data collection and provision of feedback suitable for diabetes support with increased effectiveness and low cost.

GATA3 abnormalities in six patients with HDR syndrome.

GATA3 mutations cause HDR (hypoparathyroidism, sensorineural deafness, and renal dysplasia) syndrome and, consistent with the presence of the second DiGeorge syndrome locus (DGS2) proximal to GATA3, distal 10p deletions often leads to HDR and DiGeorge syndromes. Here, we report on six Japanese patients with GATA3 abnormalities. Cases 1-5 had a normal karyotype, and case 6 had a 46,XX,del(10)(p15) karyotype. Cases 1-6 had two or three of the HDR triad features. Case 6 had no DiGeorge syndrome phenotype except for hypoparathyroidism common to HDR and DiGeorge syndromes. Mutation analysis showed heterozygous GATA3 mutations in cases 1-5, i.e., c.404-405insC (p.P135fsX303) in case 1, c.700T>C & c.708-709insC (p.F234L & p.S237fsX303) on the same allele in case 2, c.737-738insG (p.G246fsX303) in case 3, c.824G>T (p.W275L) in case 4, and IVS5+1G>C (splice error) in case 5. Deletion analysis of chromosome 10p revealed loss of GATA3 and preservation of D10S547 in case 6. The results are consistent with the previous finding that GATA3 mutations are usually identified in patients with two or three of the HDR triad features, and provide supportive data for the mapping of DGS2 in the region proximal to D10S547.

[A Phase II study of docetaxel and cisplatin in patients with recurrent or unresectable squamous cell carcinoma of the head and neck].

A Phase I / II study of docetaxel (DOC) and cisplatin (CDDP) combination therapy was conducted. The respective recommended dose (RD) in a phase I study was DOC 60 mg/m(2) and CDDP 80 mg/m(2). We performed a multicenter phase II study to assess the antitumor activity and toxicity of this RD. Patients with recurrent or unresectable squamous cell carcinoma of the head and neck were eligible. For inclusion in this study, patients were required to be >or=20<70 years of age with a Performance Status of 0 to 2. Adequate bone marrow as well as adequate renal and liver function were required. We assessed 22 patients, 13 of whom were enrolled in the phase II study, and 9 patients in phase I were given the RD. Grade 3 or higher neutropenia occurred in 12 patients (55%). There was no episode of febrile neutropenia of more than 3 days or grade 4 neutropenia of more than 3 days receiving G-CSF. Nausea was the most frequent toxicity, but only one patient experienced vomiting of more than grade 3. Pneumonia (grade 3), thrombocytopenia (grade 4) and emphysema (grade 2) were observed. No one achieved a complete response (CR) and 5 achieved a partial response (PR), for an overall response rate of 22.7% (5/22). Stable disease (SD) was seen in 11 and progressive disease (PD) in 6. In 21 of 22 patients, a relapse occurred despite previous treatment. For this population, the response rate was 19.0% (4/21).

Role of ghrelin in the regulation of vasopressin release in conscious rats.

GH secretagogue (GHS) is a small, synthetic compound that has the potential to stimulate GH release via its specific receptors (GHS-R). Ghrelin is a novel 28-amino acid peptide recently isolated from human and rat stomach, and it is thought to be the endogenous ligand for GHS-R. Ghrelin has a variety of physiological functions such as the stimulation of GH release or the increase of food intake by activating NPY neurons. In the present study, we investigated the effects of ghrelin on AVP release in conscious rats. Intracerebroventricular (icv) administration of ghrelin increased the plasma AVP concentration in a dose-dependent manner (1-1000 pmol/rat), and its effect was observed as late as 60 min after the administration. Icv injection of ghrelin caused no significant change in plasma osmolality, plasma volume, or arterial blood pressure. Iv administration of ghrelin (10 nmol/rat) also increased the plasma AVP concentration, which was accompanied by a significant decrease in arterial blood pressure. Pretreatment with antiserum against NPY significantly reduced the plasma AVP increase induced by icv administration of ghrelin. These results suggest that ghrelin plays a stimulatory role in AVP release, which is possibly mediated by NPY neurons.

Transgenic rat models of vasopressin overexpression.

Vasopressin has an important role in water metabolism and its impairment induces some clinical disorders such as diabetes insipidus or syndrome of inappropriate antidiuresis (SIAD). SIAD is caused by the overproduction of vasopressin which induces diluting hyponatremia. The accurate diagnosis and appropriate therapy have not settled up to date because its pathophysiology is very complicated. It is meaningful to develop a rat model of SIAD in which human vasopressin gene is overexpressed in order to analyze pathophysiological changes. Several models transgenic for vasopressin including us had been generated. The transgenic rats provide a useful model to investigate various pathophysiological changes resulting from the oversecretion of vasopressin. Some interesting results based on these animal models are reviewed.

Stereotactic radiosurgery as a salvage treatment for recurrent epipharyngeal carcinoma.

Fourteen patients with recurrent epipharyngeal carcinoma (EPC) were treated by gamma knife stereotactic radiosurgery. The tumor volume ranged from 0.3 to 80 ml (median 18.9 ml). Treatment was done with a tumor margin dose of 10-27 Gy (median 15 Gy). The median follow-up period was 15 months (range 2-47 months). Ten patients were alive and 4 were dead at the end of the follow-up period. In 6 patients (43%), the tumor disappeared or decreased in size until the end of the follow-up period. In 2 (14%), the tumor remained unchanged in size. In 6 (43%), the tumor showed regression initially but was enlarged later. A second radiosurgery was performed in 4 of those 6 cases and the tumor decreased in size again in 3 of them. Thus, the overall control rate of local tumor was 79% (11/14). In selected patients with recurrent EPC, stereotactic radiosurgery can be considered as a salvage treatment producing local control.

Altered cardiovascular regulation in arginine vasopressin-overexpressing transgenic rat.

Although arginine vasopressin (AVP), an antidiuretic hormone, has been widely acknowledged to play an important role in cardiovascular regulation via V1a receptors (V1aR), its precise significance remains unclear. In this study, we investigated the effects of long-standing high plasma AVP status on cardiovascular regulation in the AVP-overexpressing transgenic (Tg) rat. Adult male homozygous Tg rats were compared with age-matched normal Sprague-Dawley rats as controls. There were no significant differences in mean arterial blood pressure (BP; MABP) or heart rate between Tg and control rats in the basal state. Subcutaneous injection of AVP significantly increased MABP in controls but did not cause any apparent increase in MABP in Tg rats. BP recovery from hemorrhage-induced hypotension was significantly delayed in Tg compared with control rats. Pretreatment with a selective V1aR antagonist, OPC-21268, which is thought to restore the downregulation of V1aR, markedly improved both of these impaired responses. Northern blot analysis confirmed that decreased expression of V1aR mRNA and pretreatment with V1aR antagonist significantly restored the downregulation of V1aR mRNA. These results suggest that the Tg rat has decreased sensitivity to the hypertensive effect of AVP due to downregulation of V1aR, which may function as an adaptive mechanism to maintain normal BP against chronic hypervasopressinemia. In addition, impaired restoration of BP after hemorrhage-induced hypotension in Tg rats supports a physiological role of AVP in cardiovascular regulation.