Attainment of glycaemic goals by step-up therapy with biphasic insulin aspart-70/30 in Japanese type 2 diabetic patients

We have made step-up titration protocol with biphasic insulin aspart-70/30 (BIAsp 30), and tried to achieve glycemic goals in poorly controlled Japanese type 2 diabetic patients. We summarized all results obtained to analyze the effectiveness of our protocol. The target of glycaemic control was defined as HbA1c over 7.0 %. In our insulin initiation protocol, all patients started a once-daily injection of BIAsp 30 before the breakfast in addition to their oral hypoglycaemic agents. The patients who could not achieve the target from 12 to 16 weeks after the start of insulin treatment proceeded to twice daily insulin injection before breakfast and dinner. Next, the patients who could not achieve the target from 12 to 16 weeks after the addition of another BIAsp injection proceeded to thrice daily insulin injection before each meal a day. The results of 39 patients were analyzed, and 10.3 % of all patients achieved the target after the start of once daily injection of BIAsp 30, 41.7 % achieved in twice daily injection of BIAsp, and 51.4 % achieved in thrice daily injection of BIAsp. Daily insulin dose at the end of each treatment was 9.3±4.1 U in once daily, 17.4±6.3 U in twice daily, and 28.4±10.4 U in thrice daily. Total body weight increase by 2.0±2.6 kg. The initiation and titration protocol with BIAsp 30 improved glycaemic control, and increased the number of patients with the achievement of glycaemic goals.     

Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic antibody-associated vasculitis: report of five cases.

To minimize the adverse effects of high-dose administration of steroids and cyclophosphamide in patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA), granulocytapheresis (GCAP) or leukocytapheresis (LCAP) was performed to reduce inflammation. Four patients with rapidly progressive glomerulonephritis (RPGN) and one patient with pulmonary hemorrhage due to MPO-ANCA-associated vasculitis were treated by cytapheresis. The prednisolone (PSL) dose was 0.28 +/- 0.15 mg/kg/day (mean +/- SD) (range 0.18-0.50 g/kg/day). In the 4 RPGN patients, the peak serum creatinine level was 3.7 +/- 1.9 mg/dl (range 1.7 to 5.6 mg/dl). GCAP was performed in 3 RPGN patients and in 1 pulmonary hemorrhage patient. LCAP was performed in 1 RPGN patient. In the 4 RPGN patients, renal function improved after combined therapy with cytapheresis and corticosteroids. In the pulmonary hemorrhage patient, evidence of pulmonary hemorrhage on chest computed tomography scanning diminished after combined therapy with cytapheresis and corticosteroids. Cytapheresis, when combined with a low-dose or intermediate-dose PSL regimen, is effective in the treatment of ANCA-associated vasculitis.     

SCE-963, a New Potent Cephalosporin with High Affinity for Penicillin-Binding Proteins 1 and 3 of Escherichia coli

A few biochemical activities of SCE-963, a new cephalosporin with potent antibacterial activities against gram-negative bacteria, were compared with those of several currently available cephalosporins against strains of Escherichia coli K-12. The minimum inhibitory concentrations of SCE-963, cefazolin, cephaloridine, cephalothin, and cephalexin were 0.2, 1.56, 3.13, 12.5, and 25 mug/ml, respectively. Affinities of these cephalosporins for the penicillin-binding protein (PBP) 1B of E. coli correlated well with their antibacterial activities; among tested cephalosporins, SCE-963 showed the highest affinity for PBP 1B. SCE-963 inhibited cross-linking of peptidoglycan in a cell-free system the most strongly suggesting that this inhibition results from its high affinity for PBP 1B. SCE-963 also showed the highest affinity for PBP 3; it caused filamentation of cells over a wide range of relatively lower concentrations. Thus its superior antibacterial activity is believed to be manifested through its high affinity for the PBPs.     

Mutation analysis of the Mycobacterium leprae folP1 gene and dapsone resistance

Diaminodiphenylsulfone (dapsone) has long been used as a first-line drug worldwide for the treatment of leprosy. Diagnosis for dapsone resistance of Mycobacterium leprae by DNA tests would be of great clinical value, but the relationship between the nucleotide substitutions and susceptibility to dapsone must be clarified before use. In this study, we constructed recombinant strains of cultivable Mycobacterium smegmatis carrying the M. leprae folP1 gene with or without a point mutation, disrupting their own folP gene on the chromosome. Dapsone susceptibilities of the recombinant bacteria were measured to examine influence of the mutations. Dapsone MICs for most of the strains with mutations at codon 53 or 55 of M. leprae folP1 were 2 to 16 times as high as the MIC for the strain with the wild-type folP1 sequence, but mutations that changed Thr to Ser at codon 53 showed somewhat lower MIC values than the wild-type sequence. Strains with mutations at codon 48 or 54 showed levels of susceptibility to dapsone comparable to the susceptibility of the strain with the wild-type sequence. This study confirmed that point mutations at codon 53 or 55 of the M. leprae folP1 gene result in dapsone resistance.     

Antithrombin III loss in patients with nephrotic syndrome or receiving continuous ambulatory peritoneal dialysis. Evidence of inactive antithrombin III in urine of patients with nephrotic syndrome

Antithrombin III (AT III) was measured as antigen (Ag) and as heparin cofactor (HC) in plasma and urine or dialysate from nine patients with nephrotic syndrome and nine patients receiving continuous ambulatory peritoneal dialysis (CAPD), respectively. Crossed immunoelectrophoresis on heparin-agarose (H-CIE) and crossed immunoelectrofocusing (CIEF) runs were carried out on plasma and urine or dialysate samples. AT III plasma levels of the patients receiving CAPD were in the normal range, whereas levels in the patients with nephrotic syndrome showed a significant reduction. Nevertheless the AT III Ag daily loss was the same in both patient groups, so that an additional AT III loss caused by renal metabolism was suggested in patients with nephrotic syndrome. No alteration in the isoantithrombin plasma distribution was found in any patient. The AT III recovered in urine was almost all inactive, as demonstrated by the quantitative assays and by the H-CIE runs; on the contrary, the findings obtained by functional assays, H-CIE, and CIEF runs on dialysate samples failed to demonstrate any major alteration in the AT III molecule. In urine the AT III CIEF pattern displayed a more acid distribution (pH 4.9 to 4.5) in respect to the plasma AT III (pH 5.2 to 4.6); this pattern was suggested to be related to the renal AT III functional inactivation, whose exact mechanism remains to be clarified.     

CT-based automated planning of acetabular cup for total hip arthroplasty (THA) based on hybrid use of two statistical atlases

Purpose

This study describes the use of CT images in atlas-based automated planning methods for acetabular cup implants in total hip arthroplasty (THA). The objective of this study is to develop an automated cup planning method considering the statistical distribution of the residual thickness.

Methods

From a number of past THA planning datasets, we construct two statistical atlases that represent the surgeon’s expertise. The first atlas is a pelvis-cup merged statistical shape model (PC-SSM), which encodes global spatial relationships between the patient anatomy and implant. The other is a statistical residual thickness map (SRTM) of the implant surface, which encodes local spatial constraints of the anatomy and implant. In addition to PC-SSM and SRTM, we utilized the minimum thickness as a threshold constraint to prevent penetration.

Results

The proposed method was applied to the pelvis shapes segmented from CT images of 37 datasets of osteoarthritis patients. Automated planning results with manual segmentation were compared to the plans prepared by an experienced surgeon. There was no significant difference in the average cup size error between the two methods (1.1 and 1.2 mm, respectively). The average positional error obtained by the proposed method, which integrates the two atlases, was significantly smaller (3.2 mm) than the previous method, which uses single atlas (3.9 mm). In the proposed method with automated segmentation, the size error of the proposed method for automated segmentation was comparable (1.1 mm) to that for manual segmentation (1.1 mm). The average positional error was significantly worse (4.2 mm) than that using manual segmentation (3.2 mm). If we only consider mildly diseased cases, however, there was no significance between them (3.2 mm in automated and 2.6 mm in manual segmentation).

Conclusion

We infer that integrating PC-SSM and SRTM is a useful approach for modeling experienced surgeon’s preference during cup planning.

     

TNF-alpha induces thromboxane receptor signaling-dependent microcirculatory dysfunction in mouse liver

TNF-alpha is a critical mediator of hepatic microcirculatory dysfunction during endotoxemia. The present study was to investigate the role of thromboxane A2 (TXA2) and the biological significance of thromboxane prostanoid (TP) receptor signaling in TNF-alpha-mediated hepatic microcirculatory dysfunction in male C57Bl/6 mice. The number of leukocytes adhering to the endothelial cells of the hepatic microvessels (the portal venules, sinusoids, and central venules) and the percentage of nonperfused sinusoids were determined using in vivo fluorescence microscopy. FR167653, an inhibitor of TNF-alpha, was administered 0 and 2 h after LPS injection. A TXA2 synthase inhibitor, OKY-046, was administered 30 min before TNF-alpha injection. Thromboxane prostanoid receptor knockout mice were used to investigate whether TNF-alpha-induced hepatic microcirculatory dysfunction is mediated by endogenously produced TXA2. FR167653 reduced LPS-induced leukocyte adhesion (50%-80%) and the percentage of nonperfused sinusoids (55%). The leukocyte adhesion was increased in the portal venules (8-fold), sinusoids (51-fold), and central venules (73-fold) in TNF-alpha-treated mice, accompanied with an increase in sinusoidal perfusion deficits (8-fold). Alanine aminotransferase levels rose as the adhesion of leukocytes increased. OKY-046 administration before TNF-alpha administration reduced leukocyte adhesion (41%-49% decrease) and sinusoid perfusion deficits (34% decrease). In TP receptor knockout mice, the number of adhering leukocytes, the percentage of nonperfused sinusoids, and alanine aminotransferase levels were lower (by 43%-56%, 41%, and 29%, respectively) than in wild-type counterparts. The results suggest that TP receptor signaling may promote hepatic microcirculatory dysfunction elicited by TNF-alpha. Blockade of TNF-alpha generation and TP receptor signaling may be a good strategy for managing endotoxin-induced hepatic injury.     

Immune response to alien histocompatibility antigens on Epstein-Barr virus transformed cells

Expression of alien histocompatibility antigens on Epstein-Barr virus transformed, cultured lymphoblastoid cell lines (LCL), which were established from normal peripheral blood lymphocytes (PBL), was studied by means of mixed lymphocyte reaction (MLR), cell mediated lysis (CML) and primed lymphocyte typing (PLT). Stimulation of PBL by autologous LCL resulted in some MLR responses and generation of cytotoxic effector cells against autologous LCL. Restimulation of PBL by 16 individual allogeneic PBL failed to prime an individual lymphocytes against autologous LCL in PLT tests. However, stimulation of PBL by a pooled normal PBL resulted in generation of cytotoxic cells against autologous LCL. Culturing of stimulated PBL in the presence of T cell growth factor (TCGF) for 30 days was shown to maintain cytotoxic effector cells in the cell population.