Islet cell transplantation for the treatment of type 1 diabetes in the USA

Islet cell transplantation (ICTx) is one of the most effective treatments for type 1 diabetes and is less invasive compared to whole organ transplantation. The US has been the leader in the research and clinical applications of ICTx for the last 40 years. ICTx requires complex procedures, including pancreas procurement and preservation; pancreas digestion; islet purification; and transplantation. Even with the dramatic progresses in each of the procedures listed above, there are still challenges to make ICTx the standard therapy. These challenges are: (1) obtaining enough islets from a single donor and (2) preventing graft loss due to allogenic rejection and recurrence of autoimmune islet destruction. A new preservation strategy for pancreata and pancreatic ducts using ET-Kyoto solution as well as a new islet purification method using iodixanol has substantially improved islet yields. Continuous research to improve the efficacy of islet isolation will solve the issue of obtaining enough islets from a single donor. Immunological tolerance is an ideal solution for the issue of rejection and autoimmune recurrence and a regulatory T cell strategy seems promising. Moreover, the SUITO index is a simple and powerful tool to assess engrafted islet mass and is, therefore, useful for evaluating the efficacy of new immunosuppressant strategies. Once ICTx becomes a standard treatment, the donor shortage will become the next challenge. Marginal or living donor islet transplantations could help alleviate this issue; however, bio-artificial islet transplantation with animal islets could be the ultimate solution.     

Postoperative hip motion and functional recovery after simultaneous bilateral total hip arthroplasty for bilateral osteoarthritis

Background  Simultaneous bilateral total hip arthroplasty (THA) can offer a potential benefit of greater postoperative hip motion without the negative influence of contralateral hip disabilities, compared to two-stage THA. However, postoperative changes in hip motion after simultaneous bilateral THA have rarely been reported. The purpose of this study was to clarify the efficacy of simultaneous procedures on postoperative hip motion and functional recovery. Methods  We retrospectively compared hip motion in 27 patients treated with simultaneous bilateral THA to those in 11 patients with two-stage bilateral THA, 35 patients with unilateral THA for unilateral disease, and 15 patients with unilateral THA for bilateral disease. We also evaluated the clinical manifestations according to the Japanese Orthopaedic Association (JOA) hip scores and compared the outcomes among the groups. All of the THA surgeries were primarily performed through a posterolateral approach using cement-less prostheses. The diagnosis at surgery was dysplastic osteoarthritis in all patients, and the patients were followed up for at least 4 years. Results  The postoperative improvement of motion in hip flexion was significantly greater in patients treated with simultaneous procedures compared to patients with two-stage THA and unilateral THA for bilateral disease. The differences in improvement of motion in hip abduction were less marked than the improvement in hip flexion among the groups. Although there were no significant differences in pain scores among the groups, the values for activity of daily living were significantly greater in patients treated with simultaneous bilateral THA and patients with unilateral THA for unilateral disease than in patients with unilateral and two-stage bilateral THA for bilateral disease. Conclusions  The simultaneous procedure was considered to be more effective in patients with bilateral hip osteoarthritis and demonstrated a substantial improvement in hip motion and functional recovery after THA.     

Relation of stiffness parameter β to carotid arteriosclerosis and silent cerebral infarction in patients on chronic hemodialysis

Objective   Aortic stiffness measured by pulse wave velocity (PWV) predicts all-cause and cardiovascular mortality in hemodialysis (HD) patients. However, there is a lack of information on stiffness parameter β, another index of arterial stiffness, in HD patients. The aim of the present study was to investigate the clinical usefulness of stiffness parameter β in HD patients. Materials and methods   We compared the relation of stiffness parameter β to carotid intima-media thickness (IMT) and plaque score estimated by carotid ultrasound and investigated the relationship between stiffness parameter β and silent cerebral infarction (SCI) in 64 HD patients. Results   Stiffness parameter β was positively correlated with mean IMT (r = 0.318, P = 0.0113) and plaque score (r = 0.672, P < 0.0001). Stepwise regression analysis revealed that pulse pressure and age were found to be independent determinants of stiffness parameter β (partial correlation coefficients: β = 0.501 and P < 0.0001 for pulse pressure, β = 0.488 and P < 0.0001 for age). In addition, stiffness parameter β in patients with SCI (12.2 ± 3.9) was significantly higher than those (8.0 ± 2.4) in patients without SCI. However, there was no significant difference in mean IMT and plaque score in both groups. Conclusion   These results suggest that arteriosclerosis assessed by stiffness parameter β is associated with atherosclerotic changes of carotid arteries and with the presence of SCI in HD patients.     

High postnatal oxidative stress in neonatal cystic periventricular leukomalacia

Oxidative stress plays an important role in cystic periventricular leukomalacia (PVL). We performed a case-control study of preterm infants delivered at <35 weeks of gestation between January 2003 and December 2006. Patients were stratified into three groups, according to age at which cysts were initially identified: ?10 days old (early cystic PVL; n = 10), >10 days old (late cystic PVL; n = 12); and no cystic PVL (controls; n = 22). Serum total hydroperoxide, biological antioxidant potential and oxidative stress index (calculated as total hydroperoxide/biological antioxidant potential) were measured within 3 h after birth. Frequencies of preterm rupture of membrane and chorioamnionitis were significant higher in early cystic PVL than in late cystic PVL or controls. Duration of oxygen treatment and mechanical ventilation and frequency of apnea were significantly higher in late cystic PVL than in controls or early cystic PVL. Serum total hydroperoxide levels and oxidative stress index were significantly higher in early cystic PVL than in late cystic PVL or controls (p < 0.05, respectively). Postnatal duration until cyst identification displayed a significant negative correlation with oxidative stress index and total hydroperoxide level (r = −0.497, p < 0.05; r = −0.50, p < 0.05, respectively). These findings suggest that early onset of cystic PVL might be due to either antenatal or intrapartum factors, but late onset might be due to postnatal factors. In the pathophysiology and therapy of cystic PVL, oxidative stress and onset timing appear crucial. This is the first study to reveal that neonates experiencing much more oxidative stress at birth show earlier onset of cystic PVL.     

Retinal astrocyte differentiation mediated by leukemia inhibitory factor in cooperation with bone morphogenetic protein 2

Retinal astrocytes and their precursor cells migrate from the optic nerve. Interleukin 6 family cytokines, whose signal transduction requires gp130, promote astrocyte differentiation in the optic nerve, though the mechanism of astrocyte differentiation in the retina has not been clarified. We found that GFAP-positive astrocytes were significantly decreased in number but that a considerable number of astrocytes were still present in gp130-deficient mouse retina. These findings suggest that gp130-dependent signaling pathways play essential roles in retinal astrocyte differentiation and that retinal astrocyte differentiation can also be promoted by other signaling pathways. We found that leukemia inhibitory factor, bone morphogenetic proteins, and their receptors are expressed in P0 retina. In addition, leukemia inhibitory factor and bone morphogenetic protein 2 synergistically promote astrocyte differentiation of retinal precursor cells isolated from P0 mouse retina. These observations demonstrated that not only gp130-dependent signaling but also bone morphogenetic proteins play essential roles in retinal astrocyte differentiation.     

Risk factors for open heart surgery in hemodialysis patients

Purpose  There have been many reports on open heart surgery in hemodialysis patients; however, the mortality rates in these patients are higher than those in nonhemodialysis patients. The purpose of this study was to identify the risk factors for mortality following open heart surgery in hemodialysis patients. Methods  We evaluated 76 consecutive patients (76/2030 total open heart surgeries, 3.7%) who required hemodialysis before open heart surgery between January 1990 and January 2008. There were 46 men and 30 women (mean age 63 ± 11 years). The mean duration of hemodialysis was 9 years 5 months (8 months to 30 years). Chronic glomerulonephritis (25 cases, 33%) and diabetic nephropathy (17 cases, 22%) were the most common diseases leading to a requirement for hemodialysis. Operations included 36 coronary artery bypass grafting (CABG) cases (48%; emergency/elective 22: 14), 24 aortic valve replacements (AVR) (34%), and 9 cases of concomitant AVR plus CABG (12%). Multivariate logistic analyses were performed to identify the risk factors. No patient was lost during follow-up. Results  The overall in-hospital mortality rate was 17.1% (13/76). The 5-year survival rate was 39% ± 8%. Univariate logistic analysis showed that age (>70 years), low-output syndrome (ejection fraction <40% and/or intraaortic balloon pump support), and concomitant surgery were significant risk factors for mortality. Multivariate logistic analysis suggested that only concomitant surgery was the significant risk factor (odds ratio 4.37, P = 0.007). Conclusion  Concomitant surgery is a significant risk factor for mortality following open heart surgery in hemodialysis patients. This study was partially presented at the 58th annual meeting of the Japanese Association for Thoracic Surgery, Okayama, October 2005.     

Serum carcinoembryonic antigen level in non-small-cell lung cancer patients with preoperative normal serum level

Objective  The prognostic significance of serum carcinoembryonic antigen (CEA) levels in non-small-cell lung cancer (NSCLC) patients with a normal serum CEA level (<5.0 ng/ml) was examined. Methods  A total of 220 consecutive NSCLC patients with preoperative normal serum CEA levels were included. Patients were subdivided into two groups: preoperative serum CEA level ≥2.5 and <2.5 ng/ml. Results  The 5-year survival of patients with preoperative serum CEA level less and more than 2.5 ng/ml were 79.62% and 62.0%, respectively (P = 0.0036). Multivariate analysis indicated that a preoperative serum CEA level of ≥2.5 ng/ml was an independent prognostic factor. Similar results were found in patients with adenocarcinoma but not found in others. Conclusion  NSCLC patients with a high serum CEA level, especially adenocarcinoma patients, had poorer prognosis even if their serum CEA levels were within the normal upper limit.