Usefulness of magnetic resonance imaging of the wrist for the early diagnosis of dialysis-related amyloidosis

Dialysis-related amyloidosis (DRA) is a major complication of long-term hemodialysis patients. The onset of arthropathy is frequently preceded by carpal tunnel syndrome, but the early non-invasive diagnosis of DRA remains unclear. beta 2-microglobulin amyloid deposits in joint synovia and soft tissue precede radiological abnormalities. Magnetic resonance imaging (MRI) may play a more important role in the early diagnosis of DRA, because it allows direct visualization of synovitis and deposition of abnormal soft tissue. The purpose of this study was to evaluate the usefulness of MRI of the wrist for the early diagnosis of DRA. The study included 72 patients (male 37, female 35) undergoing hemodialysis from initiation to 20 years. The patients were examined by MR images of synovitis, deposition of abnormal soft tissue and cystic bone lesions at the wrists. Normal MR images of synovia and soft tissue were defined in 6 control subjects (2 normal 4 non-dialysis patients). Synovitis of the carpal bones was found in 23% of the patients at the start of hemodialysis. Deposition of abnormal soft tissue in the carpal canal and cystic bone lesions were detected after 1 and 2 years of hemodialysis, respectively. All findings were increased significantly with an increasing duration of dialysis. Synovitis was present in 90% of the patients with deposition of abnormal soft tissue, and in 80% of the patients with cystic bone lesions. beta 2-microglobulin value was significantly higher in patients with synovitis, deposition of abnormal soft tissue and cystic bone lesions than in patients without these findings. Our experience suggest that synovitis examined by MRI of the wrists is useful for the early diagnosis of DRA. Thereby, intensive follow-up and management of DRA are required in patients with synovitis at the start of hemodialysis.     

Morphology and barrier function of the corneal epithelium after penetrating keratoplasty: association with original diseases, tear function, and suture removal.

PURPOSE: To study changes in structure and barrier function of the corneal epithelium after penetrating keratoplasty. METHODS: Sixty-nine eyes of 56 patients undergoing penetrating keratoplasty were studied. Fifty-six age-matched normal eyes served as controls. Corneal epithelial structure was studied by using specular microscopy. Barrier function of the corneal epithelium was examined by slit-lamp fluorophotometry. Vital staining, tear function, and corneal sensitivity also were examined. RESULTS: Fluorescein and rose bengal staining scores, incidence of elongated cells, the mean epithelial area, and mean fluorescein uptake were significantly increased in postkeratoplasty eyes compared with controls. Original disease influenced the results of barrier function, where keratoconus revealed better function than bullous keratopathy or corneal scar. However, no such differences were noted in epithelial structure. Six eyes with absence of palisades of Vogt had revealed significantly increased epithelial area and fluorescein uptake. Removal of the running suture caused a decrease in elongated cells and epithelial cell area without significant changes in barrier function. CONCLUSION: Corneal epithelial structure was significantly impaired in postkeratoplasty eyes. Epithelial barrier function of postkeratoplasty eyes was influenced by original diseases. Removal of sutures improves epithelial structure but not barrier function.     

In vivo release of neuronal histamine in the hypothalamus of rats measured by microdialysis

Summary Using an in vivo intracerebral microdialysis method coupled with an HPLC-fluorometric method, we investigated the extracellular level of endogenous histamine in the anterior hypothalamic area of urethaneanaesthetized rats. The basal rate of release of endogenous histamine in the anterior hypothalamic area measured by this method was 0.09 + 0.01 pmol/20 min. When the anterior hypothalamic area was depolarized by infusion of 100 mM K⁺ through the dialysis membrane or electrical stimulation at 200 A was applied through an electrode implanted into the ipsilateral tuberomammillary nucleus, histamine release increased to 175% and 188%, respectively, of the basal level. These increases were completely suppressed by removal of extracellular Ca²⁺. The basal release of histamine was also suppressed after infusion of 10^–6 M tetrodotoxin or i.p. administration of 100 mg/kg of -fluoromethylhistidine. On the other hand, 3-fold increase in the basal release was observed after i. p. administration of 5 mg/kg thioperamide. These results clearly indicate that both the basal and evoked release of histamine measured by our method are of neuronal origin. Send offprint requests to T. Mochizuki at the above address     

Cytokine production in surgical stress

Surgical injury influences the function of mononuclear cells, leading to various systemic responses. Proinflammatory cytokines such as tumor necrosis factor alpha (TNF alpha), interleukin (IL)-1, -6, -8, and the antiinflammatory cytokine IL-10, which are mainly produced by mononuclear cells, are known to play an important role in the response to and pathogenesis of surgical stress. TNF alpha production by monocytes is extremely upregulated, but monocyte HLA-DR antigen expression is suppressed in patients with surgical stress. While production of Th1 cytokines such as IL-12 and interferon-gamma by mononuclear cells is suppressed, production of Th2 cytokines and IL-10 is upregulated during surgical stress. Immune suppression following surgical stress has been clarified recently in terms of Th1 and Th2 cytokine production balance mainly caused by mononuclear cells. It is thought to be very important to maintain immunological function after surgical stress by controlling cytokine production and balance.     

Development of a miniature undulation pump for the distributed artificial heart

Research of the distributed artificial heart is important not only to acquire the means of individual organ perfusion but also to clarify the characteristics of the organ and the mechanism of blood distribution. To investigate the distributed artificial heart, the miniature undulation pump was developed. The outer diameter and the thickness of the developed pump were 38 mm and 11 mm, respectively. The priming volume of the pump was 3.2 ml. The total size including the motor unit was 38 mm in diameter and 32 mm in length. The total weight was 67.5 g. The total volume was 27.5 ml. The pump was driven with pulse width modulation by using a 1 chip motor controller. More than 5 L/min of continuous output could be obtained. The results showed that the developed miniature undulation pump system had enough performance for individual organ perfusion.     

Radioresponse of Thymomas Verified with Histologic Response

Patterns of radiologic response of 10 thymomas treated by preoperative radiotherapy (RT) (18-20 Gy/2 weeks) were determined in conjunction with histologic response. Changes in tumor volume were evaluated with CT scans obtained 5 to 36 days before and 14 to 24 days after the initiation of RT and before surgery. The extent of tumor volume reduction (TR) varied widely (40-78%), while the mean daily volume decrement expressed as a percentage of the pre-RT tumor volume correlated significantly with the pre-RT tumor volume. Histologically, the tumors, all of which were resected 17 to 33 days after RT initiation, generally consisted of predominant fibrous tissues, rare necrotic foci, and few epithelial cells. The TR did not correlate with pre-RT tumor volume, observation period, histologic subtype, or quantity of remaining epithelial cells. The TR of thymomas does not predict RT impact on tumor cells but does reflect the quantity of inherent tumor stroma.     

Selection of Human Ovarian Carcinoma Cells with High Dissemination Potential by Repeated Passage of the Cells in vivo into Nude Mice, and Involvement of Lex-determinant in the Dissemination Potential

Cells of the human tumor cell line RMG-1, derived from a clear-cell adenocarcinoma of the ovary, were injected intraperitoneally into nude mice, and the cells obtained from the tumor nodules in the mesenterium were found to form a larger number of, and larger-sized, tumor nodules than the original RMG-1 cells. The RMG-1-h cells, transferred into culture from the tumor nodules after a 4th in vivo passage, showed a dissemination potential as high as that of cells disseminating directly from the tissues, and exceedingly higher than that of RMG-1 cells. To assess the molecular bases of the different biological properties of RMG-1 and RMG-1-h cells, we compared the content and expression of various carbohydrate antigens in both cells. The chromosomal profile of RMG-1-h cells revealed their human origin and was identical to that of the original RMG-1 cells. In contrast to the broad histogram for the Le^x-bearing cells among RMG-1 cells in flow cytometry, the weakly and moderately positive cells toward anti-Le^x antibody were found to be eliminated from the histogram for the RMG-1-h cells, resulting in the enrichment of cells strongly expressing Le^x, which may account for the high dissemination potential. In addition, the adhesion of RMG-1 cells to mesothelial cells was found to be significantly inhibited by pretreatment of the cells with anti-Le^x antibody, indicating Le^x-mediated cell-to-cell interaction between ovarian cancer cells and mesothelial cells. By TLC-immunostaining, two Le^x-glycolipids, III³Fucα-nLc₄Cer and V³Fucα-nLc₆Cer were detected in both RMG-1 and RMG-1-h cells, and their total concentrations were not significantly different from each other. However, the hydrophobic moieties of Le^x-glycolipids in RMG-1-h cells were different from those in RMG-1 cells, suggesting that a difference in the structure of the hydrophobic moieties of Le^x is partly involved in the enhanced reactivity of RMG-1-h cells toward anti-Le^x antibody. Thus, the high dissemination potential of ovarian cancer cells was shown to be mediated by the Le^x-determinant and the Le^x-bearing cells are enriched by repeated in vivo passage of the cells into nude mice.