CORRELATIONS BETWEEN VIDEO CAPSULE ENDOSCOPIC FINDINGS AND CLINICAL ACTIVITY IN CROHN’S DISEASE

Background and Aims: Video capsule endoscopy (VCE) has become increasingly important as a simple method for observing the entire small intestine. The indications for VCE are obscure gastrointestinal bleeding and investigation of Crohn’s disease (CD). However, the correlation between endoscopic findings obtained by VCE and clinical findings in known cases of CD is not clear, and we therefore investigated this in the present study. Patients and methods: In 30 patients with known CD (Crohn’s disease activity index [CDAI] 0–420; median = 158.3), double contrast enteroclysis (ENT) was performed 1–3 weeks prior to VCE. The relationship between the VCE findings and hematological analysis/CDAI was examined. Results: In 17 of 30 patients, the entire small intestine could be investigated by VCE, whereas in the remaining 13 patients the terminal ileum could not be investigated. The following exhibited positive correlations: total lesions and CDAI (correlation coefficient values: r_s = 0.661, adjusted P < 0.0061), ulcers and C‐reactive protein (CRP) (r_s = 0.607, adjusted P < 0.0061), total lesions and CRP (r_s = 0.604, adjusted P < 0.0061). Conclusions: Analysis with VCE suggests that CDAI and CRP indicate the activity of intestinal lesions in patients with known CD, and that CRP, in particular, is associated with the activity of ulcerative lesions of the intestine. This may contribute to revised guidelines for VCE in the future.     

Preparation of two-drug composite microparticles to improve the dissolution of insoluble drug in water for use with a 4-fluid nozzle spray drier.

In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water.     

Coronary artery bypass grafting with combined arterial grafts

Coronary artery bypass grafting with combined arterial graft using the left internal mammary artery (IMA), right IMA, and the right gastroepiploic artery (GEA) was performed in 45 patients with saphenous vein graft (SVG) (29 patients) or without SVG (16 patients) from February 1989 to October 1989. The left IMA was used in all patients, the right IMA was used in 9 patients, and the GEA was used in 43 patients. Perioperative myocardial infarction was noted in two patients who had hospital deaths. Reopening the chest for postoperative bleeding was performed in two patients, and the cerebral accident was noted in one patient. Fourteen patients were operated on without the requirement for blood transfusion. Studied within 3 postoperative months, all arterial grafts were patent though the patency was 97.7% (43/44) in SVG. It is concluded that the combined arterial graft utilizing the IMAs and GEA can be used safely and effectively.     

N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve.

Axonal pathology is a major cause of neurological disability in multiple sclerosis. Axonal transection begins at disease onset but remains clinically silent because of compensatory brain mechanisms. Noninvasive surrogate markers for axonal injury are therefore essential to monitor cumulative disease burden in vivo. The neuronal compound N-acetylaspartate, as measured by magnetic resonance spectroscopy, is currently the best and most specific noninvasive marker of axonal pathology in multiple sclerosis. The possibility has been raised, however, that N-acetylaspartate is expressed also by oligodendroglial lineage cells. In order to investigate N-acetylaspartate specificity for white matter axons, transected rat optic nerves were analyzed by high-performance liquid chromatography and immunohistochemistry. In transected adult nerves, N-acetylaspartate and N-acetyl aspartylglutamate decreased in concordance with axonal degeneration and were undetectable 24 days posttransection. Nonproliferating oligodendrocyte progenitor cells, oligodendrocytes, and myelin were abundant in these axon-free nerves. At 24 days posttransection, N-acetylaspartate was increased (42%; p = 0.02) in nontransected contralateral nerves. After transection at postnatal day 4, total N-acetylaspartate decreased by 80% (P14; p = 0.002) and 94% (P20; p = 0.003). In these developing axon-free nerves, 25 to 33% of oligodendrocyte progenitor cells were proliferating. These data validate magnetic resonance spectroscopy measurements of N-acetylaspartate as an axon-specific monitor of central nervous system white matter in vivo. In addition, the results indicate that neuronal adaptation can increase N-acetylaspartate levels, and that 5 to 20% of the N-acetylaspartate in developing white matter is synthesized by proliferating oligodendrocyte progenitor cells.     

Development of a simple analytical method to determine the serum concentration of denopamine by high performance liquid chromatography with electrochemical detection and its clinical application

Denopamine (DP) is a new, orally active, selectively positive inotropic agent and used for the treatment of chronic cardiac insufficiency. The therapeutic effects of DP is highly related to its serum concentrations. A simple analytical method has been developed to determine the serum concentration of DP by use of high performance liquid chromatography (HPLC) with electrochemical detection (ECD). In order to extract the DP from the serum, a disposable solid extraction column (Sep-Pak cartridge, C-18) was used. The average recovery was 84.6 +/- 2.7%. The working electrode potential was fixed at 400 mV with a T1 cell, 600 mV with a T2 cell and 650 mV with a Guard cell in ECD. The analysis was performed on a Nova-Pak cartridge C-18 reverse-phase column (100 mm X 8 mm i.d., 4 microns). The mobile phase consisted of 0.1 M potassium phosphate buffer (pH 6.0) and acetonitrile (83: 17, v/v), and the flow rate was 1.0 ml/min. DP and internal standard phenolphthalein (PP) were eluted at 16.5 and 36.0 min, respectively. The peak-height ratio of DP to PP was linearly correlated (r = 0.9998) over a concentrations range between 1.25 and 15.0 ng/ml in the serum. The lowest detectable concentration was 1.0 ng/ml in the serum. The coefficient of variation of reproducibility in the assay was 6.0% By using the present method, serum concentration of DP was measured for four healthy volunteers after a single oral administration of 10 mg DP tablet after a overnight fast. From these DP concentration profiles, pharmacokinetic parameters were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)