Relationship between progression of diabetic retinopathy and blood glucose control

The relationship between the progression of diabetic retinopathy and consecutive blood sugar control measured by HbA1 levels was statistically analyzed based on 422 eyes of 211 diabetic patients who were followed up 2 years or more. Cox regression (proportional hazard model) with HbA1 as a time-dependent covariate was applied and the relative risk of HbA1 vis-à-vis the progression of retinopathy was evaluated. For a given value of HbA1 at each time point during progression, the average for x preceding months was calculated and the value of x was changed from 1 to 30 to assess the cumulative effect of HbA1. The cumulative effect of HbA1 was statistically significant and the absolute value of the coefficient changed little if the periods for calculating the average are equal to or more than 6 months. Relative risks corresponding to the increase of HbA1 (averaged at 6 months) by 1, 2 and 3% were 1.18, 1.39 and 1.63, respectively. When the HbA1 level was adjusted to its average value (9.56%), estimated cumulative progression rates for 6, 12, 18 and 24 follow-up months were 3.6, 14.5, 22.5 and 30.5%, respectively. Difference of cumulative progression rate between a well-controlled group with a low (3% less than the average) HbA1 value and a poorly-controlled group with a high (3% higher than the average) HbA1 value was estimated as 3% (6 follow-up months) and 23% (24 months).     

Flow cytometric analysis of cellular DNA content of lung cancer with reference to survival

The cellular DNA content of lung cancer were measured by flow cytometry on 223 paraffin-embedded specimens prepared from resected lung carcinomas. According to the histological type of lung cancer, the mean values for the DNA Index were 1.41 in adenocarcinoma, 1.39 in squamous cell carcinoma, 1.33 in large cell carcinoma and 1.84 in small cell carcinoma. The DNA Index of small cell carcinoma was thus slightly higher than that of the other histological types, without statistically significant difference. Of 223 lung carcinoma cases, 131 (59.1%) were DNA aneuploidy and 92 (40.9%) were DNA diploidy. DNA aneuploidy was found in 56.1% of adenocarcinomas, 59.5% of squamous cell carcinomas, 53.3% of large cell carcinomas and 100% of small cell carcinomas. According to the staging of the lung cancer, the mean values of the DNA Index were 1.40 in stage I, 1.46 in stage II, 1.36 in stage IIIA, 1.48 in stage IIIB and 1.48 in stage IV. No statistically significant differences were found among these stages. DNA aneuploidy was found in 57.1% of stage I, 57.9% of stage II, 54.7% of stage IIIA, 60.0% of stage IIIB and 75.0% of stage IV. The correlation of DNA content with survival were investigated in 94 cases with stage I non-small cell carcinoma which underwent absolute curative resection. Of 94 cases, the 5-year survival rate of 40 cases with DNA diploidy was 81.1% and a mean survival time 111 months, while this one of the remaining 54 with DNA aneuploidy was 58.4% and a mean survival time 80 months.(ABSTRACT TRUNCATED AT 250 WORDS)     

Patient radiation dose reduction using an X-ray imaging noise reduction technology for cardiac angiography and intervention

Coronary angiography and intervention can expose patients to high radiation dose. This retrospective study quantifies the patient dose reduction due to the introduction of a novel X-ray imaging noise reduction technology using advanced real-time image noise reduction algorithms and optimized acquisition chain for fluoroscopy and exposure in interventional cardiology. Patient, procedure and radiation dose data were retrospectively collected in the period August 2012–August 2013 for 883 patients treated with the image noise reduction technology (referred as “new system”). The same data were collected for 1083 patients in the period April 2011–July 2012 with a system using state-of-the-art image processing and reference acquisition chain (referred as “reference system”). Procedures were divided into diagnostic (CAG) and intervention (PCI). Acquisition parameters such as fluoroscopy time, volume of contrast medium, number of exposure images and number of stored fluoroscopy images were collected to classify procedure complexity. The procedural dose reduction was investigated separately for three main cardiologists. The new system provides significant dose reduction compared to the reference system. Median DAP values decreased for all procedures (p < 0.0001) from 172.7 to 59.4 Gy cm², for CAG from 155.1 to 52.0 Gy cm² and for PCI from 229.0 to 85.8 Gy cm² with reduction quantified at 66, 66 and 63 %, respectively. Based on median values, the dose reduction for all procedures was 68, 60 and 67 % for cardiologists 1, 2 and 3, respectively. The X-ray imaging technology combining advanced real-time image noise reduction algorithms and anatomy-specific optimized fluoroscopy and cine acquisition chain provides 66 % patient dose reduction in interventional cardiology.     

Large-scale production and properties of human plasma-derived activated Factor VII concentrate

BACKGROUND AND OBJECTIVES: An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. MATERIALS AND METHODS: FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. RESULTS: Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. CONCLUSIONS: We established a large-scale manufacturing process of human plasma-derived FVIIa concentrate with a high yield, making it possible to provide sufficient FVIIa concentrate for use in haemophiliacs with inhibitory antibodies.     

Characteristic gene expression induced by polyurethane foam/spheroid culture of hepatoma cell line, Hep G2 as a promising cell source for bioartificial liver

BACKGROUND/AIMS: Polyurethane foam (PUF)/ spheroid-culture can improve liver-specific functions of hepatoma cell line, Hep G2. Therefore, gene expression profile in the PUF/spheroid culture is hypothesized to be different from that in the monolayer culture. The aim of this study is to clarify the characteristic gene expression in PUF/spheroid-cultured Hep G2 cells, as a cell source for bioartificial liver (BAL), using microarray analysis. METHODOLOGY: Morphological change and liver specific functions of ammonia removal rate and albumin synthesis rate of Hep G2 were compared between in a monolayer or PUF/spheroid culture. Microarray analysis was performed using cDNA microarrays made in Hitachi Software Engineering Co., Ltd., (Yokohama, Japan), which contains a total of 1,281 cDNA clones. RESULTS: The ammonia removal rate of Hep G2 spheroids increased to 369%, and the albumin synthesis rate of Hep G2 spheroids also increased 311% when compared with monolayer culture. In addition, the ammonia removal capacity of primary human hepatocytes in the PUF/spheroid culture was superior to that in the monolayer culture. The microarray analysis demonstrated that the PUF/spheroid-cultured Hep G2 cells expressed 39 up-regulated (more than 3.0-fold) and 31 down-regulated (less than 0.333-fold) genes. Among the 70 genes differentially expressed in PUF/spheroid cultured Hep G2 cells, subsets of glutathione S-transferase- and angio-tensin-related genes were drastically up-regulated, on the other hand, subsets of assigned for growth factor, glucocorticoid, and stress response, were down-regulated. CONCLUSIONS: Hepatoma cell line, Hep G2 cells in the PUF/spheroid culture is a promising hepatocyte source for BAL. Microarray analysis revealed a number of characteristic genes altered by the PUF/spheroid.     

Catheter ablation of fatal ventricular tachyarrhythmias storm in acute coronary syndrome—role of Purkinje fiber network

Ventricular fibrillation (VF) or ventricular tachycardia (VT) storm is a life-threatening arrhythmia. Antiarrhythmic drugs (AADs) are not necessarily effective to rescue life from such conditions. Catheter ablation (CA) targeting triggering premature ventricular contractions (PVCs) of VF or VT that originates from Purkinje fiber network (PFN) is reported to be effective, especially in idiopathic patients. However, in condition of acute coronary syndrome (ACS), the efficacy of CA is not well understood. To clarify the usefulness of CA as an alternative way to AADs, we performed CA in four patients with VF or VT storm. The Purkinje potential was seen just before the myocardial ventricular wave during sinus rhythm that became more prominent and double components during the initiating PVC at the targeted area. Following CA, spontaneous episodes of VF or VT were no longer observed. CA is an efficacious way to bail out PFN-related VF or VT storm even in ACS.     

Macular microcirculation before and after vitrectomy for macular edema with branch retinal vein occlusion

Background  

The changes of perifoveal capillary blood flow velocity (BFV), visual acuity, and retinal thickness after pars plana vitrectomy (PPV) have been unclear in patients with branch retinal vein occlusion (BRVO) and macular edema.