Comparison of ulinastatin, gabexate mesilate, and nafamostat mesilate in preservation solution for islet isolation

For islet transplantation, maintaining organ viability after pancreas procurement is critically important for optimal graft function and survival. We recently reported that islet yield was significantly higher in the modified ET-Kyoto (MK) solution, which includes a trypsin inhibitor (ulinastatin), compared with the UW solution, and that the advantages of MK solution are trypsin inhibition and less collagenase inhibition. In this study, we compared ulinastatin with other trypsin inhibitors, gabexate mesilate, and nafamostat mesilate, in preservation solution for islet isolation. Ulinastatin was easily dissolved in ET-Kyoto solution, while ET-Kyoto with gabexate mesilate and nafamostat mesilate became cloudy immediately after addition. Although there were no significant differences in islet yield among the three groups, viability was significantly higher for the MK group than for the GK group or the NK group. The stimulation index was significantly higher for the MK group than for the GK group. In summary, there are no other trypsin inhibitors that are more effective than ulinastatin. Based on these data, we now use ET-Kyoto solution with ulinastatin for clinical islet transplantation.     

Anesthetic management for a patient with multiple sclerosis at exacerbation stage under general anesthesia

A 39-year-old woman with multiple sclerosis (MS) at exacerbation stage underwent dilatation and curettage. MS is characterized by chronic inflammation, demyelination, and gliosis in the central nervous system. Surgical stress often induces exacerbation of MS symptoms. Therefore, deep anesthesia is required for anesthetic management in cases of MS. We monitored electroencephalograph (EEG), spectral edge frequency 90 (SEF 90), spectral median frequency (SMF) and delta-amplitude for depth of anesthesia using pEEG (Dr?ger, Germany). In this case, anesthesia was induced with sevoflurane and gradually increased to 5% in oxygen 4 l.min-1 and maintained with sevoflurane 2-3% in 2 nitrous oxide l.min-1 and 2 l.min-1 oxygen. Surgery was completed and no spike wave was observed by pEEG monitoring during surgery. In conclusion, sevoflurane anesthesia was useful for a patient with MS during exacerbation stage.     

Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes

Diabetic nephropathy is a leading cause of end-stage renal failure. Several mechanisms, including activation of protein kinase C, advanced glycation end products, and overexpression of transforming growth factor (TGF)-beta, are believed to be involved in the pathogenesis of diabetic nephropathy. However, the significance of inflammatory processes in the pathogenesis of diabetic microvascular complications is poorly understood. Accumulation of macrophages and overexpression of leukocyte adhesion molecules and chemokines are prominent in diabetic human kidney tissues. We previously demonstrated that intercellular adhesion molecule (ICAM)-1 mediates macrophage infiltration into the diabetic kidney. In the present study, to investigate the role of ICAM-1 in diabetic nephropathy, we induced diabetes in ICAM-1-deficient (ICAM-1(-/-)) mice and ICAM-1(+/+) mice with streptozotocin and examined the renal pathology over a period of 6 months. The infiltration of macrophages was markedly suppressed in diabetic ICAM-1(-/-) mice compared with that of ICAM-1(+/+) mice. Urinary albumin excretion, glomerular hypertrophy, and mesangial matrix expansion were significantly lower in diabetic ICAM-1(-/-) mice than in diabetic ICAM-1(+/+) mice. Moreover, expressions of TGF-beta and type IV collagen in glomeruli were also suppressed in diabetic ICAM-1(-/-) mice. These results suggest that ICAM-1 is critically involved in the pathogenesis of diabetic nephropathy.     

Relative contribution of lean and fat mass component to bone mineral density in males

 We investigated the relative contribution of lean body mass (LBM) and body fat mass to bone mineral density (BMD) in 93 healthy Japanese male volunteers (mean age, 33.1 ± 6.9 years; range, 18–54 years). Age, height (Ht), weight (Wt), and body mass index (BMI, Wt/Ht²) were recorded. Body fat mass, percentage of body fat, body fat mass/Ht², LBM, LBM/Wt, LBM/Ht², and lumbar spine (L2–L4) and total body BMD (TBBMD) were measured by dual-energy X-ray absorptiometry. On the Pearson correlation test, LBM was positively correlated with L2–L4 BMD. LBM, LBM/Wt, and LBM/Ht² were positively correlated with TBBMD. However, body fat mass and body fat mass/Ht² were not correlated with lumbar spine and total body BMD. On the partial correlation test, LBM was still correlated with lumbar spine (r = 0.307, P < 0.05) and total body BMD (r = 0.545, P < 0.0001), irrespective of age and height, whereas body fat mass was not correlated with BMD of these sites (r = −0.069 and −0.169, respectively). We concluded that, in males, LBM is one of the significant determinants of BMD whereas body fat mass is a negligible BMD determinant. Received: February 15, 2002 / Accepted: July 5, 2002 Offprint requests to: T. Douchi     

Comparison of plasma levels of mature adrenomedullin and natriuretic peptide as markers of cardiac function in hemodialysis patients with coronary artery disease

BACKGROUND: It has been suggested that, like ANP and BNP, high plasma levels of mature adrenomedullin (mAM) indirectly reflect the severity of heart failure or renal failure. However, the relationship between mAM levels and hemodynamics and cardiac function has not been examined in hemodialysis (HD) patients with coronary artery disease (CAD). The best marker, among mAM, ANP and BNP, for left-ventricular function in those patients is also unclear. PATIENTS AND METHODS: Plasma levels of mAM, total AM (tAM), ANP and BNP were determined before HD in chronic HD patients with CAD (group 1; n = 17) and were compared with those of HD patients without cardiac disease (group 2; n = 22). We examined their relationship to hemodynamics and cardiac function in group 1 using data obtained by cardiac catheterization. RESULTS: Plasma levels of ANP and BNP were significantly higher in group 1 than in group 2, but there was no significant difference in plasma levels of mAM and tAM between the two patient groups. Plasma levels of both mAM and tAM significantly correlated with right atrial pressure (RAP), and only plasma tAM levels correlated with pulmonary artery pressure (PAP) and pulmonary artery wedge pressure (PAWP). However, no correlations were found between levels of the two forms of AM and ejection fraction (EF). In contrast, plasma ANP and BNP levels significantly correlated with both PAP and PAWP, and also with EF, although they did not correlate with RAP. The correlation of PAP and PAWP with ANP and BNP levels was closer than that with tAM levels. The most significant correlation was between BNP levels and EF (r = -0.756, p < 0.0001). CONCLUSIONS: Our results suggest that the mAM level may be less useful than natriuretic peptide levels as a marker of cardiac function in HD patients with CAD, and that the BNP level might be the best indicator of left-ventricular function. In addition, cardiac disease such as CAD may have a minor impact on mAM levels compared to renal failure.     

Possible role of soluble erythropoietin receptors in renal anemia

Recombinant human erythropoietin(rHuEpo) is effective for the treatment of renal anemia associated with chronic renal failure(CRF). However, we have encountered some patients with CRF who have sometimes developed a resistance to rHuEpo. This resistance can be due to iron or folate deficiency, aluminum toxicity, hyperparathyroidism, or auto-antibodies for rHuEpo. In this study, we focused on the soluble erythropoietin receptor(sEpoR), which can bind to rHuEpo. To demonstrate the possibility that the sweeping of rHuEpo by sEpoR results in resistance to rHuEpo, we performed a bioassay using the rHuEpo-dependent cell line, UT7/EPO. The results showed that recombinant mouse sEpoR(rmsEpoR) can reduce the proliferation of UT7/EPO induced by rHuEpo in a dose-dependent manner. We consider that this cell line could be a useful tool in a bioassay to detect the inhibitory factor(s) against Epo. We selected sera from three groups of patients with renal anemia associated with CRF who were receiving hemodialysis three times a week: the first was a patient group that needed a high dose of rHuEpo(7,500-9,000 unit/dialysis), the second was a patient group that needed an intermediate dose of rHuEpo (4,500 unit/dialysis), the third was a patient group that needed a low dose of rHuEpo(below 1,500 unit/dialysis). Interestingly, the proliferation of UT7/EPO determined with [3H]-thymidine incorporation was reduced by the addition of sera from the first group, but not by the addition of sera from the third group. These results suggested that serum sEpoR may play an important role in signal transduction via EpoR on erythroid progenitor in CRF patients.     

Comparison of methods of steroid administration combined with tonsillectomy for IgA nephropathy patients

Background

IgA nephropathy (IgAN) is a chronic glomerular disease that causes end-stage renal disease in 20–40 % of patients within 20 years. The efficacy of tonsillectomy combined with steroid pulse (SP) administration (TSP) for clinical remission of IgAN has been reported. Particularly in Japan, TSP has been performed widely. However, the optimum method for steroid administration in TSP has not been established.

Methods

We retrospectively compared clinical remission in IgAN patients treated with tonsillectomy combined with two different steroid administration methods: (1) three courses of SP therapy and oral prednisolone administered on alternate days (group 3A; n = 25); and (2) one course of SP therapy and oral prednisolone administered on consecutive days (group 1C; n = 22).

Results

There was no significant difference in the clinical remission rates between the two groups at 12 (48.0 vs. 40.9 %, P = 0.77) and 24 months after starting treatment (68.0 vs. 72.7 %, P = 0.76) and at the final observation (76.0 vs. 81.8 %, P = 0.73). The mean period from starting treatment to remission of hematuria in group 3A was significantly shorter than that in group 1C (5.7 ± 4.4 vs. 9.9 ± 5.9 months, P = 0.03). Dyslipidemic patients treated for the first time with statin after the SP therapy were more present in group 3A at 24 months (P = 0.02).

Conclusions

In IgAN patients, treatment of group 3A may be effective for inducing rapid remission of hematuria. Further studies are needed to establish an appropriate protocol for TSP.

     

Case of tuberculous epididymitis caused by intravesical BCG therapy

Intravesical Bacillus Calmette-Guerin (BCG) therapy is commonly used against superficial urothelial carcinoma, especially carcinoma in situ (CIS). We report a case of tuberculous epididymitis that occurred during a course of intravesical BCG therapy. A 76-year-old man had received intravesical BCG therapy for multiple superficial bladder cancer and CIS in prostatic urethra after transurethral resection of bladder tumor (TUR-Bt). He recognized hard nodules in the left scrotum after 4 times intravesical BCG therapy. Skin fistula in scrotum occurred 5 months later. We performed left orchiectomy with scrotum skin resection. Histological diagnosis was tuberculous epididymitis. Postoperatively, he was administered chemotherapy consisting of isoniazid, refampin and ethambutol.     

Long-term outcome of hand-assisted laparoscopic radical nephrectomy for localized stage T1/T2 renal-cell carcinoma

PURPOSE: To evaluate the efficacy of hand-assisted laparoscopic radical nephrectomy (HALRN) in patients with localized stage T(1)/T(2) renal-cell carcinoma, we analyzed the clinical results of our patients treated in this way. PATIENTS AND METHODS: From March 1999 to March 2003, a total of 96 patients aged 28 to 86 years (mean 61 years) with clinical stage T(1)/T(2)N(0)M(0), pathologically confirmed renal-cell carcinoma underwent HALRN. The outcomes were compared with those of open radical nephrectomy, which was performed in 86 patients from November 1991 to February 1999 in our institution. Kaplan-Meier analysis was used to analyze survival. RESULTS: Ten patients (10.4%) had perioperative complications. During a mean follow-up of 25 months (range 6-54 months), no patients died of the cancer, although three patients had metastatic disease. The 4-year disease- free and overall survival rates were 88% and 100%, respectively. Seventy-eight patients who underwent open radical nephrectomy were followed for 38 to 156 months (median 86 months). Seventy-three survived without any recurrent disease, five survived with metastasis, and no patient died of metastatic disease. The 4-year disease-free and overall survival rates were 93% and 100%, respectively. CONCLUSIONS: Hand-assisted laparoscopic surgical management of T(1)/T(2) renal-cell carcinoma is feasible and safe. At our institution, HALRN confers long-term oncologic effectiveness equivalent to that of open radical nephrectomy.