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The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy.

By geometric analysis of real-time 3-dimensional echocardiography performed in 39 patients with hypertrophic obstructive cardiomyopathy and definite systolic anterior motion of the mitral valve, we found that the angle between the mitral annular plane and basal portion of the anterior mitral valve leaflet, and the angle between the basal portion of the anterior leaflet and its tip portion measured in the medial and central anteroposterior planes, were significantly smaller than those in the lateral plane. The distance between the interventricular septum and the anterior mitral valve tip in the medial and central plane was also significantly smaller than that in the lateral plane. The lateral distance between the interventricular septum and the anterior mitral valve tip was the only independent determinant of left ventricular outflow tract pressure gradient by multiple stepwise regression analysis. In conclusion, systolic anterior motion of the mitral valve develops predominantly in the medial side, resulting in laterally located narrow left ventricular outflow tract opening in patients with hypertrophic obstructive cardiomyopathy.

We evaluated the significance of the diastolic-to-systolic blood flow velocity ratio (DSVR) determined by transthoracic Doppler echocardiography, for a physiologic assessment of the severity of coronary stenosis without stress tests, as compared with thallium 201 single photon emission computed tomography. In 95 patients undergoing thallium 201 single photon emission computed tomography for coronary artery disease, the flow velocity in the distal left anterior descending coronary artery was obtained with transthoracic Doppler echocardiography. The mean and peak DSVR values were calculated using mean and peak coronary flow velocity. DSVR was successfully measured for 82 patients (86.3%), including 33 patients with reversible perfusion defects in the left anterior descending coronary artery territories. For predicting reversible perfusion defects in thallium 201 single photon emission computed tomography, the best cut-off points were 1.5 for mean DSVR (sensitivity 81.8%, specificity 85.7%) and 1.6 for peak DSVR (sensitivity 75.7%, specificity 83.6%). Noninvasive measurement of DSVR with transthoracic Doppler echocardiography provides physiologic estimation of the left anterior descending coronary artery stenosis severity at high success rate, without stress tests.

Abstract: Acute intermittent porphyria (AIP) is an autosomal-dominant disease caused by a deficiency of porphobilinogen (PBG) deaminase. Patients with AIP present with neurological syndromes such as autonomic neuropathy, peripheral axonal neuropathy or central nervous system dysfunction. We report serial MRI of a patient with AIP who had cortical and subcortical cerebral changes. A 29-year-old woman with a 6-month history of AIP had an attack with severe hyponatraemia and generalised convulsions, treated with haem arginate and supportive therapy. MRI showed central pontine and extrapontine myelinolysis and cortical laminar necrosis. These are not common in AIP, but are likely to have been caused by rapid correction of hyponatraemia and by vasospasm, which could be induced by AIP.

Gastric inhibitory polypeptide (GIP) and truncated glucagon like peptide-1 (tGLP-1) are potent gastrointestinal insulinotropic factors (incretin), mostly released after a meal or ingestion of glucose in man and animals. To investigate whether sulfonylurea (SU) affects the secretion of incretin, the modulation of plasma GIP and tGLP-1 levels following glucose ingestion in non-insulin-dependent diabetic type 2 patients with or without SU therapy was studied. A 75-g oral glucose tolerance test (OGTT) was carried out on 9 healthy subjects (controls) and 18 patients with non-obese type 2, 9 of whom were treated by diet alone (NIDDM-diet) and the other 9 with SU (glibenclamide 2.5 mg or gliclazide 40 mg) once a day (NIDDM-SU). Plasma GIP was measured by radioimmunoassay (RIA) with R65 antibody, and GLP-1 was measured by RIA with N-terminal-directed antiserum R1043 (GLP-1NT) and C-terminal-directed antiserum R2337 (GLP-1CT). Following OGTT, plasma glucose, GIP, GLP-1NT, and GLP-1CT in type 2 patients increased more markedly than in controls, despite the lower response of insulin. However, there were no significant differences in plasma levels of these peptides between the NIDDM-diet and NIDDM-SU groups. Therefore, it is unlikely that SU is involved in the high response of GIP and GLP-1s to OGTT in type 2 patients.

The fluidity of mortar containing a polycarboxylate-based high-range water-reducing AE agent was studied with respect to the change in fluidity with time after the mixing, and the influence of the kind and amount of calcium sulfate in the belite-rich cement with a low interstitial phases was discussed. The flow of belite-rich cement mortar immediately after the mixing initially increased and then decreased with the increase in the saturation ratio of the liquid phase with respect to CaSO4·2H2O. On the other hand, the flow loss continuously decreased with the increase in the saturation ratio. The saturation ratio of the liquid phase strongly depended on the amount of CaSO4·0.5H2O, and was hardly affected by the other kinds of calcium sulfate. The adsorption of the agent inversely corresponded to the mortar flow immediately after the mixing. However, the flow loss did not coincide with the adsorption tendency. It is suggested that the steric hindrance remains to some degree after the hydrate partially covers the agent adsorbed on the cement particles.

OBJECTIVE: To examine if there is a correlation between high blood glucose and serum ceruloplasmin (Cp) levels. RESEARCH DESIGN AND METHODS: Serum Cp levels were measured in 637 patients with type 2 diabetes (all type 2 diabetes group). For the follow-up type 2 diabetes group, 161 patients who had not had any changes in their situation during the last year that are known to influence serum Cp levels were reexamined 1 year later. The control group was composed of 158 healthy individuals. Serum Cp and blood HbA1c levels were measured by radial immunodiffusion and high-performance liquid chromatography assays, respectively. RESULTS: Serum Cp levels in the all type 2 diabetes group were significantly higher than those in the control group (P < 0.0001), although the serum Cp levels did not correlate with the blood HbA1c levels in the all type 2 diabetes group (r = 0.055, P = 0.351). Then we evaluated those factors (delta-log Cp and delta-HbA1c) in the follow-up type 2 diabetes group to minimize changes from the genetic differences and to exclude any known factors influencing serum Cp levels. This indicated that the delta-HbA1c had a positive correlation to the delta-log Cp (r = 0.304, P < 0.0001). CONCLUSIONS: A persistent high blood glucose (namely HbA1c) is associated with an increase in serum Cp levels over 1 year.

The nucleotide sequence of messenger RNA encoding rat liver aldolase B has been determined by sequence analysis using recombinant cDNAs cloned in bacterial plasmids. The sequence contains part of the 5‘-untranslatable region (68 nucleotides), the entire coding region (1092 nucleotides), and the complete 3‘-untranslatable region (387 nucleotides), excluding the poly(A) tail. A potential ribosomal-binding site is located about 30 nucleotides upstream from the initiation codon. The amino acid sequence of rat liver aldolase B is composed of 364 amino acids and has 70% homology with rabbit muscle aldolase A.

Human insulin-like growth factor II (IGF-II) cDNA from a placental library was isolated and sequenced. The 5' untranslated region (5'-UTR) sequence of this cDNA differs completely from that of adult human liver and has considerable base sequence identity to the same region of an IGF-II cDNA of a rat liver cell line, BRL-3A. Human placental poly(A)+ RNA was probed with either the 5'-UTR of the isolated human placental IGF-II cDNA or the 5'-UTR of the IGF-II cDNA obtained from adult human liver. No transcripts were detected by using the 5'-UTR of the adult liver IGF-II as the probe. In contrast, three transcripts of 6.0, 3.2, and 2.2 kilobases were detected by using the 5'-UTR of the placental IGF-II cDNA as the probe or the probe from the coding sequence. A fourth IGF-II transcript of 4.9 kilobases presumably containing a 5'-UTR consisting of a base sequence dissimilar to that of either IGF-II 5'-UTR was apparent. Therefore, IGF-II transcripts detected may be products of alternative splicing as their 5'-UTR sequence is contained within the human IGF-II gene or they may be a consequence of alternative promoter utilization in placenta.

Spot size and peak intensity of a light spot focused by a GRIN rod lens using a collimated laser-diode beam were measured as a function of the amount of defocus and of lens tilt. Assuming only primary spherical aberration, the wave aberration of the GRIN lens was estimated by diffraction theory taking the presence of aberrations into account. In a point-to-point imaging system, the spot size was measured as a function of the distance between lens and light source.

A novel mutation of the ceruloplasmin (Cp) gene was found in a patient with hereditary ceruloplasmin deficiency (HCD) with diabetes mellitus (DM). The patient had been treated for DM for about 13 years, and then his illness was diagnosed as HCD. One year later, he was found dead in his home. A decrease in insulin-immunostained cells was observed in the islets of the patient′s pancreas tissue, which accounted for his DM. The polymerase chain reaction (PCR)-direct sequencing analysis of the Cp gene of his daughter revealed a novel point mutation, G to A, at nucleotide 2630 in exon 15. This mutation changes the Trp858codon (TGG) to a stop codon (TAG) (nonsense mutation). PCR-restriction analysis for the mutation revealed that the patient as well as his daughter was a heterozygote for the mutation, indicating that the patient was a compound heterozygote.

We characterized the genomic region corresponding to the human ceruloplasmin cDNA previously reported. Using PCR-direct sequencing methods, we determined precise intron/exon boundaries and intron-exon composition of the gene in the region. The gene region spanned about 50 kb and was composed of 19 exons and 18 introns. The lengths of exons and introns range from 107 to over 267 bp and from 0.44 to 10.0 kb, respectively. The translation initiation codon and the termination codon were located in exons 1 and 19, respectively. The nucleotide sequences of the introns were also determined in the region around the intron/exon boundaries for 24 - 220 bp. All the sequences around the intron/exon boundaries were consistent with the 5′ and 3′ consensus sequences for splice junctions of transcribed genes. Putative lariat sequences were identified between −17 and −42 nucleotides from the 3′ splice junction for all 18 introns.

Heterogeneity of zonal hepatocytes is important to elicit specific liver function. We investigated the distribution of glucose transporter 2 (GLUT-2) in normal rat liver by immunostaining and Northern blot analysis. GLUT-2 stained by immunohistochemistry was distributed predominantly in the periportal hepatocytes and gradually thinned towards the perivenous zone. Ultrastructural immunostaining of GLUT-2 showed that it was localized on microvilli of the sinusoidal plasma membrane of hepatocytes but not on the basolateral plasma membrane. Consistent with the distribution of GLUT-2 protein, the level of GLUT-2 mRNA in periportal hepatocytes was 1.9-fold higher than in perivenous hepatocytes selectively isolated by the differential isolation technique. In addition, the mRNA level of phosphoenolpyruvate carboxykinase, one of the key enzymes of gluconeogenesis, was also twofold higher in the periportal hepatocytes. These results suggest that GLUT-2 contributes to the functional difference between periportal and perivenous hepatocytes in glucose metabolism of the liver.

Abstract: We present two patients with hypocaeruloplasminaemia and a heteroallelic caeruloplasmin gene mutation (HypoCPGM). These patients had diabetes mellitus and tremor of the hands, respectively. T2-weighted fast spin-echo MRI showed mildly reduced intensity of the putamen, much more marked on echo-planar imaging.

Abstract: Hereditary coproporphyria (HCP) is an autosomal dominant disease characterized by a deficiency of coproporphyrinogen oxidase. To date, four mutations of the gene have been reported. We report here another mutation in two Japanese families with HCP, which was revealed by analysis of polymerase chain reaction (PCR)-amplified DNA fragments of the gene by a direct-sequencing method. A point mutation, G to A, was found in exon 4 of the gene at position 538 of the cDNA from the reported putative translation initiation codon ATG. This mutation results in a glycine to arginine substitution at amino acid 180. Two carriers in the family were successfully diagnosed by detecting the mutation using restriction analysis of the PCR products.

Purpose. We previously re-validated noninvasive estimation of pulmonary wedge pressure (PWP) measuring the CW pulmonary valve regurgitation end-diastolic pressure gradient (PWPecho). Using the latter as surrogate of PWP, we sought to test accuracy of left ventricular (LV) filling pressures estimation by the EAE guidelines algorithm (EAEalg) in a large non-selected population. Methods. We studied 1019 patients in sinus rhythm with GE Vivid7/9 systems (age: 10-93 y.; EF%: 13-83%, normal, n= 827 and reduced <50%, n= 192), in whom PWPecho could be measured (feasibility 75%), with normal pulmonary vascular resistances (WU< 2). The EAEalg combined E/e' (average), left atrial volume (LAV), E/A, Edec, pulmonary venous systolic fraction (SF), and echo-derived pulmonary systolic pressure (PSPe) to obtain 3 groups: normal, high PWP and not classifiable. These were compared to the PWPecho estimate. Results: Feasibility was high for all variables (E/E' 90%, LAV 93%, E/A 95%, Edec 90%, SF 91%, PSPe 92%), and for the EAEAlg (94%). Using the EAEAlg, 17% (n=137) of patients with normal in contrast to 10% (n=19) of patients with EF<50% were not classifiable, in the former secondary to the combination of a E/E'= 9-13 range, and LAV≥ 34ml/m2. In the remaining (classified, 84%) patients, utility of EAEalg even when limited to patients with EF<50% was still hampered by a low positive predictive value (PPV) (Table). Further, when only E/e' was tested in the same patients at ROC analysis (cutoff= 15; AUC=0.72, CI:0.6-0.8), accuracy was still impaired by a low PPV (53%), albeit a fair negative predictive value (NPV) (79%). Correlation between PWPecho and E/e' was modest even in patients with EF<50% (r=0.4, p<0.001), and at multiple regression analysis, E/e' was independently determined by age and mitral regurgitation in all patients, and by LV end-diastolic volume in EF<50% (r= 0.7, p<0.001) and by LV mass index in EF>50% (r= 0.64, p<.001). Conclusions. Noninvasive estimation of PWP by EAE guidelines is limited by a low PPV in both patients with and without reduced LV EF. In this setting, utility of the E/e' is limited, it being influenced by patient age, preload and LV mass. 1 SensitivitySpecificityPPVNPVEF≥50%72%78%18%98%EF<50%71%80%65%84%

Aim To develop age-, sex-, and ethnic-appropriate normative reference ranges for standard echocardiographic measurements of the left heart by combining echocardiographic measurements obtained from adult volunteers without clinical cardiovascular disease or significant cardiovascular risk factors, from multiple studies around the world. Methods and results The Echocardiographic Normal Ranges Meta-Analysis of the Left heart (EchoNoRMAL) collaboration was established and population-based data sets of echocardiographic measurements combined to perform an individual person data meta-analysis. Data from 43 studies were received, representing 51 222 subjects, of which 22 404 adults aged 18–80 years were without clinical cardiovascular or renal disease, hypertension or diabetes. Quantile regression or an appropriate parametric regression method will be used to derive reference values at the 5th and 95th centile of each measurement against age. Conclusion This unique data set represents a large, multi-ethnic cohort of subjects resident in a wide range of countries. The resultant reference ranges will have wide applicability for normative data based on age, sex, and ethnicity.

Purpose: Cardiac deconditioning due to immobilization is a risk factor for cardiovascular disease. The physiology of cardiac adaptation to deconditioning has not been fully elucidated. The purpose of the present study was to assess the effects of 21-days of strict head-down (-6 degrees) bed-rest (BR) deconditioning on left ventricular (LV) dimensions and mass measured by MRI. Methods: Ten healthy men (mean age 32±6) were enrolled; the experiment was conducted at DLR (Koln, Germany) as part of the European Space Agency BR studies. Steady-state free precession MRI images (7mm thickness, no gap, no overlap) were obtained (Symphony 1.5T, Siemens) in a stack of short-axis views from LV base to LV apex, before (PRE), at the end of BR (HDT20), and four days after the BR conclusion (POST). Endocardial and epicardial semi-automated contouring was performed using freely available software (Segment). Results: At HDT20, significant reductions in LV mass (16%), end-diastolic (26%) and end-systolic (27%) volumes and stroke volume (27%) were observed, while ejection fraction did not change. These changes were accompanied by a measured decrease (14%) in plasma and blood volume (by gas-rebreathing technique), as well as by a significant reduction (14%) in VO2max aerobic power, measured using a graded cycle ergometer test protocol to volitional fatigue, at one day after the BR conclusion, while expiratory exchange ratio did not change. At POST, LV volumes were restored, while LV mass was still trending towards control values. Conclusions: Cardiac adaptation to deconditioning affected LV mass and dimensions, as a combined result of LV remodeling and fluids loss, accompanied by worsening in aerobic power. This should be taken into account in patients with cardiovascular diseases, when immobilized in bed, to proper adjust the therapy, or to define appropriate physical exercises when possible, in order to avoid further complications.   Cardiac MRI parameters PREHDT20POSTLV mass (g)121±6102±11*114±16End-diastolic volume (ml)119±2590±14*118±25End-systolic volume (ml)42±831±8*45±14Stroke volume (ml)76±2259±11*73±15Ejection fraction (%)64±665±762±7 *: p<.01 vs PRE (one-way Anova for paired data and Tukey test)

BaFI:Eu phosphors are fabricated using a new method of synthesis: liquid phase synthesis, in which the phosphor particles are formed through the association of Ba2+ ions, F- ions and Eu2+ ions in solution. An intense optically stimulated luminescence (OSL) peak at about 410 nm is observed by stimulating X ray irradiated BaFI:Eu phosphor with about 550-750 nm light. It is found that the peak wavelength of the optically stimulation spectrum is about 690 nm. This result suggests that the semiconductor laser can be used as the stimulating light source. It is also found that the OSL intensity is increased with increasing the X ray dose. The BaFI:Eu phosphor as a photostimulable material for the imaging place of a computed radiography system provides the following advantages: (1) high X ray absorption coefficient, (2) high monodispersion in size which would contribute to sharp images, (3) high OSL and thus low luminescence mottle and (4) high DQE (detective quantum efficiency).