Lipoatrophic diabetes. Report of a case

The female patient initially showed the acquired type of total lipoatrophy at about 8 years of age. At 12 years of age, the onset of diabetes mellitus was speculated from advanced pyodermia and dedentition. At 29 years of age, glucosuria was found, and she developed proteinuria, ascites, and pretibial edema. The physical examination revealed: hepatosplenomegaly, complete absence of subcutanous fat, cutaneous xanthomas, and emaciated facies with pronounced zygomatic arches. Diabetic retinopathy was revealed in the ophthalmological examination, and nephropathy was evident in renal biopsy specimens. She also had peripheral diabetic neuropathy. No adipose tissue was found in the mesenterium under peritoneoscopy. The hepatic biopsy specimen revealed advanced portal liver cirrhosis. Laboratory findings included: hyperlipidemia, elevation of BMR without evidence of hyperthyroidism, impaired renal function, and undetected anti-insulin antibodies and anti-insulin antibodies. Endocrinological examinations revealed normal value, except for an impaired hGH response in the arginine test. C-peptide immunoreactivity was high. Her condition was fairly well controlled by 140 units of insulin injection daily.</p

Potential endocrine effects of hypothalamic peptide "neurotensin" on pancreas in dogs

Effects of synthetic neurotensin on the endocrine pancreas were studied in nine normal and six hypophysectomized (10th to 14th day post-hypophysectomy) dogs. Synthetic neurotensin was administered into the superior pancreaticoduodenal artery, and plasma insulin and glucagon concentrations were measured radioimmunologically. In normal dogs, ten microgram/kg neurotensin administration brought about a mild hyperglycemic response and sharp and rapid increase of plasma insulin and glucagon concentrations in the superior pancreaticoduodenal vein. A biphasic insulin response was noted in the pancreatic vein. The results suggest that a large dose of neurotensin acts directly on the endocrine pancreas causing secretion of these hormones. In hypophysectomized dogs, basal levels of plasma insulin and glucagon were decreased and neurotensin had little effect on the endocrine pancreas even with the administration of a large dose.</p

A novel atrial volume reduction technique to enhance the Cox maze procedure: Initial results

ObjectiveLarge left atrial diameter is reported to be a predictor for recurrent atrial fibrillation after the Cox maze procedure, and left atrial diameter by itself influences the chance of sinus rhythm recovery, as well as maintenance of sinus rhythm. However, additional cut-and-sew procedures to decrease left atrial diameter extend operative time and can cause bleeding. Thus we developed a no-bleeding, faster, and therefore less invasive left atrial volume reduction technique to enhance the Cox maze procedure.MethodsThe modified Cox maze III procedure with cryoablation or the left atrial maze procedure in association with mitral valve surgery was performed in 80 patients with atrial fibrillation and enlarged left atria (≥60 mm). Among them, 44 patients had the concomitant volume reduction technique (VR group); continuous horizontal mattress sutures for left atrial plication were placed on the left atrial wall along the pulmonary vein isolation line. Cryoablation was applied to the suture line so that the plicated left atrium is anatomically and electrically isolated. Another 36 patients did not have the volume reduction technique (control group).ResultsThe VR group had preoperative left atrial diameters similar to those of the control group (67.1 ± 7.8 vs 64.5 ± 6.7 mm) and a longer preoperative duration of atrial fibrillation (14.1 ± 5.4 vs 9.5 ± 5.1 years, P < .05) but had smaller postoperative left atrial diameters (47.6 ± 6.3 vs 62.1 ± 7.9 mm, P < .01). There were no differences in mean crossclamp/bypass time and chest tube drainage for 12 hours between the groups. Twelve months after surgical intervention, the sinus rhythm recovery rate of the VR group was better than that of the control group (90% vs 69%, P < .05).ConclusionsEven in patients with long-standing atrial fibrillation and an enlarged left atrium, maze procedures concomitant with the novel left atrial volume reduction technique improved the sinus rhythm recovery rate without increasing complications. Although further study with a larger number of patients and a longer follow-up period is needed, this safe and thus far potent technique that catheter-based ablation cannot copy might extend indication of the Cox maze procedure for patients with tough atrial fibrillation

Estrogen Prevents Bone Loss via Estrogen Receptor α and Induction of Fas Ligand in Osteoclasts

SummaryEstrogen prevents osteoporotic bone loss by attenuating bone resorption; however, the molecular basis for this is unknown. Here, we report a critical role for the osteoclastic estrogen receptor α (ERα) in mediating estrogen-dependent bone maintenance in female mice. We selectively ablated ERα in differentiated osteoclasts (ERαΔOc/ΔOc) and found that ERαΔOc/ΔOc females, but not males, exhibited trabecular bone loss, similar to the osteoporotic bone phenotype in postmenopausal women. Further, we show that estrogen induced apoptosis and upregulation of Fas ligand (FasL) expression in osteoclasts of the trabecular bones of WT but not ERαΔOc/ΔOc mice. The expression of ERα was also required for the induction of apoptosis by tamoxifen and estrogen in cultured osteoclasts. Our results support a model in which estrogen regulates the life span of mature osteoclasts via the induction of the Fas/FasL system, thereby providing an explanation for the osteoprotective function of estrogen as well as SERMs

Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER)

BackgroundAlternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer.Patients and methodsEligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival.ResultsOf 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75–88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7–9.5 months). The median overall survival was 23.1 months (95% CI 17.4–28.8 months). The response rate was 44% (95% CI 30.2–57.8%), and the disease control rate was 88% (95% CI 79.0–97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events.ConclusionS-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies

Algorithmic Versus Expert Human Interpretation of Instantaneous Wave-Free Ratio Coronary Pressure-Wire Pull Back Data

Objectives The aim of this study was to investigate whether algorithmic interpretation (AI) of instantaneous wave-free ratio (iFR) pressure-wire pull back data would be noninferior to expert human interpretation. Background Interpretation of iFR pressure-wire pull back data can be complex and is subjective. Methods Fifteen human experts interpreted 1,008 iFR pull back traces (691 unique, 317 duplicate). For each trace, experts determined the hemodynamic appropriateness for percutaneous coronary intervention (PCI) and, in such cases, the optimal physiological strategy for PCI. The heart team (HT) interpretation was determined by consensus of the individual expert opinions. The same 1,008 pull back traces were also interpreted algorithmically. The coprimary hypotheses of this study were that AI would be noninferior to the interpretation of the median expert human in determining: 1) the hemodynamic appropriateness for PCI; and 2) the physiological strategy for PCI. Results Regarding the hemodynamic appropriateness for PCI, the median expert human demonstrated 89.3% agreement with the HT in comparison with 89.4% for AI (p < 0.01 for noninferiority). Across the 372 cases judged as hemodynamically appropriate for PCI according to the HT, the median expert human demonstrated 88.8% agreement with the HT in comparison with 89.7% for AI (p < 0.0001 for noninferiority). On reproducibility testing, the HT opinion itself changed 1 in 10 times for both the appropriateness for PCI and the physiological PCI strategy. In contrast, AI showed no change. Conclusions AI of iFR pressure-wire pull back data was noninferior to expert human interpretation in determining both the hemodynamic appropriateness for PCI and the optimal physiological strategy for PCI

Immunoreactive dog C-peptide levels in pancreatic vein Part Ⅲ: Study of the feedback regulation of pancreatic B cell secretion by exogenous insulin

Feedback regulation of insulin secretion from dog pancreatic B cells by exogenous insulin was demonstrated. Dog C-peptide immunoreactivity (CPR) concentration in the superior pancreaticoduodenal (pancreatic) vein was measured as an index of endogenous insulin secretion from B cells. Exogenous monocomponent (MC) insulin was administered into superior pancreaticoduodenal (pancreatic) artery of normal dogs which had various concentrations of blood glucose. When the blood glucose level was maintained at about 400 mg/dl, bolus injection of MC insulin (0.1 u/kg) into the pancreatic artery caused about 8.3% suppression of CPR level in the pancreatic vein. However, when the blood glucose concentration was approximately 180 mg/dl, suppression of the CPR level in the pancreatic vein was about 41%. With a fasting blood glucose concentration, exogenous MC insulin caused about 35% suppression of CPR level, but exogenous dog C-peptide (0.2 pM/kg/min) infusion did not affect the IRI concentration in the pancreatic vein

Immunoreactive dog C-peptide levels in pancreatic vein Part Ⅱ: Effects of CNS active agents on pancreatic B cells; neurotensin, xenopsin, gammer hydroxibutyric acid (GHB) 2-Br-a-ergocryptin (CB154), pimozide, substance-P

Immunoreactive dog C-peptide [CPR] and insulin [IRI] concentration in the superior pancreaticoduodenal (pancreatic) vein of normal dogs were measured after administration of neurotensin, xenopsin, γ-hydroxybutyric acid [GHB], 2-Br-α-ergocryptine [CB154], pimozide, and substance-P into the superior pancreaticoduodenal (pancreatic) artery. The effect of neurotensin on B cell secretion was studied in hypophysectomized (10th to 14th day post-hypophysectomy) dogs. In normal dogs, the administration of synthetic neurotensin (10 μg/kg) induced a mild hyperglycemic response with parallel and biphasic increases in both CPR and IRI levels. In hypophysectomized dogs, basal levels of pancreatic CPR and IRI were reduced to about 14% and 55% of the control, respectively. Neurotensin had little effect on pancreatic B cell secretion. Administration of synthetic xenopsin (10 μg/kg) caused mild hyperglycemia and rapid equimolar increases of CPR and IRI in the pancreatic vein. GHB had suppressive effects on both CPR and IRI secretion. Administration of a high dose (500 mg/kg) of GHB showed a more marked decrease in CPR and IRI than that of the low dose (100 mg/kg). The degree of suppression in CPR and IRI secretion was nearly equimolar. A bolus injection of CB154 (200 mg/kg) had caused mild hyperglycemia and biphasic CPR and IRI increases, but after premedication with pimozide (1 mg/kg, i.m.) the same dose of CB154 administration resulted in decrease of CPR and IRI concentrations in the pancreatic vein. With infusion of synthetic substance-P (50 ng/kg/min) for 30 min, CPR and IRI concentrations in the pancreatic vein were reduced parallel and were nearly equimolar. The above findings indicated that C-peptide and insulin were released from the B cell in equimolar concentrations after stimulation by various CNS affecting agents

Immunoreactive dog C-peptide levels in pancreatic vein Part I: Dog C-peptide radioimmunoassay and C-peptide immunoreactivity in pancreatic vein after loading of glucose and arginine

A specific dog C-peptide radioimmunoassay system was established with a single antibody method using synthetic dog C-peptide as standard. The measurable range was between 0.4 pM/ml and 25.6 pM/ml. The coefficients of variation of Within and Between-assay were 6.0 and 10.8%, respectively. Dog C-peptide immunoreactivity (CPR) and immunoreactive insulin (IRI) level in the superior pancreaticoduodenal (pancreatic) vein were measured in fasting and after loading of glucose or arginine into the superior pancreaticoduodenal (pancreatic) artery. Fasting dog CPR level was 2.73 ± 0.46 pM/ml in the pancreatic vein and was 0.67 ± 0.03 pM/ml in peripheral vein. The molar ratio of CPR/IRI was 1.42 in the pancreatic vein and 6.09 in peripheral vein. Glucose (10 mg/kg/min) infusion into the pancreatic artery evoked a prompt and parallel maximal increase in CPR and IRI within 3 min. The CPR concentration increased from 3.1 pM/ml to 6.5 pM/ml and the IRI concentration increased from 1.7 pM/ml to 4.6 pM/ml at the peak. Arginine (250 mg/kg/min) infusion resulted in a prompt, parallel increase in CPR and IRI. The CPR concentration increased from 3.2 pM/ml to 5.8 pM/ml, and the IRI concentration from 1.7 pM/ml to 4.4 pM/ml at 40 sec, respectively. The insulin - to - C-peptide ratio showed approximately equimolarity

Development of evaluation for sinter ore mixing using discrete element method

Recent increase of low-grade, finer iron ore leads to development of powder handling methodology applicable for fine powders. In order to reduce developing time of mechanical facilities, development of optimization methodology of mechanical property in powder mixer was conducted. This methodology was combination of mixing experiment and novel discrete element method (DEM). Conventional DEM tracks particle movements to evaluate mixing of particles; in this model in addition enabled to evaluate moisture content as it tracked exchange of moisture content between particles upon contact. This DEM model was validated in comparison with experimental PIV surface flow and DEM surface flow, in lab-scale (diameter of 390 mm) of high speed shear mixer. Using this method enabled to estimate mixing time of high speed shear mixer with accuracy of t &lt; 10 s where estimation time varied from around 20 to 100 s