Donor islet endothelial cells in pancreatic islet revascularization

OBJECTIVE

Freshly isolated pancreatic islets contain, in contrast to cultured islets, intraislet endothelial cells (ECs), which can contribute to the formation of functional blood vessels after transplantation. We have characterized how donor islet endothelial cells (DIECs) may contribute to the revascularization rate, vascular density, and endocrine graft function after transplantation of freshly isolated and cultured islets.

RESEARCH DESIGN AND METHODS

Freshly isolated and cultured islets were transplanted under the kidney capsule and into the anterior chamber of the eye. Intravital laser scanning microscopy was used to monitor the revascularization process and DIECs in intact grafts. The grafts’ metabolic function was examined by reversal of diabetes, and the ultrastructural morphology by transmission electron microscopy.

RESULTS

DIECs significantly contributed to the vasculature of fresh islet grafts, assessed up to 5 months after transplantation, but were hardly detected in cultured islet grafts. Early participation of DIECs in the revascularization process correlated with a higher revascularization rate of freshly isolated islets compared with cultured islets. However, after complete revascularization, the vascular density was similar in the two groups, and host ECs gained morphological features resembling the endogenous islet vasculature. Surprisingly, grafts originating from cultured islets reversed diabetes more rapidly than those originating from fresh islets.

CONCLUSIONS

In summary, DIECs contributed to the revascularization of fresh, but not cultured, islets by participating in early processes of vessel formation and persisting in the vasculature over long periods of time. However, the DIECs did not increase the vascular density or improve the endocrine function of the grafts.Clinical islet transplantation can restore endogenous insulin production and glycemic control in patients with type 1 diabetes, yet increased knowledge, and hence refinement, would allow for a wider application of this therapy (1). Pancreatic islets are interspersed by a dense and tortuous capillary network that facilitates an efficient exchange of oxygen, nutrients, and hormones between the endocrine cells and the bloodstream. Transplanted islets are revascularized by blood vessels that grow into the islets from the host organ via angiogenesis (2), although the acquired vasculature has a significantly lower vessel density compared with the endogenous islets (3). Furthermore, during the initial avascular engraftment period, a dramatic reduction in insulin content and high rate of cell death occur within the islets (4). Therapies that enhance the angiogenic capacity of islets by overexpression of vascular endothelial growth factor-A (VEGF-A) can increase the vascular density of islet grafts and improve metabolic function (5,6).Recently, we and others showed that donor islet endothelial cells (DIECs) can form functional vessels within transplanted islets (7,8). Immediately after isolation (i.e., in freshly isolated islets), a large number of intraislet endothelial cells (ECs) are present (7–9). However, if the islets are cultured, the intraislet ECs rapidly disappear, and by 4 days, only ∼5% of the initial content is detected (7). Therefore, freshly isolated islets, in contrast to cultured islets, contain an extra pool of ECs that potentially could promote islet revascularization and function after transplantation. Here, we have performed a detailed characterization of the role of DIECs in the revascularization of transplanted islets.     

Peri-operative electrically evoked auditory brainstem response assessment of facial nerve/cochlea interaction at cochlear implantation

Objectives: Dehiscence between the cochlear otic capsule and the facial nerve canal is a rare and relatively newly described pathology. In cochlear implantation (CI), this dehiscence may lead to adverse electric facial nerve stimulation (FNS) already at low levels, rendering its use impossible. Here, we describe an assessment technique to foresee this complication.

Methods: Pre- and postoperative computed tomography (CT) scans and intraoperative electrically evoked auditory brainstem response (e-ABR) measurements were analyzed in two patients with cochlear-facial dehiscence (CFD).

Results: Because of the relatively low resolution, the confirmation of CFD with a clinical CT was difficult. The e-ABR displayed a large potential with 6 and 7.5?ms latency, respectively, which did not occur otherwise.

Discussion: Potential strategies to resolve and manage FNS are described.

Conclusion: Prediction of FNS by assessing the distance between the labyrinthine portion of the facial nerve and the cochlea is difficult using conventional CT scans. A large evoked late myogenic potential at low stimulation levels during intraoperative e-ABR measurement may foresee FNS at CI activation.     

Cholangiography during laparoscopic cholecystectomy—Cumulative sum analysis of an institutional learning curve

The ability to perform intraoperative cholangiography during laparoscopic cholecystectomy is an essential skill for the laparoscopic biliary surgeon. The volume of experience required to be able to consistently obtain a cholangiogram during laparoscopic cholecystectomy has not been determined. Cumulative sum analysis is a statistical technique which generates a graphical display that identifies periods of performance that fell below a predetermined standard for a given task. The cumulative sum (S_n) for a series of observations is defined as: ie185-001 where X₁ = 0 for a success, X₁ = 1 for a failure, and X₀ is the acceptable failure rate for the process under study. This function is plotted against the number of observations to create a curve. When the curve has a positive slope, the acceptable failure rate is being exceeded. When it reaches a plateau, the observed failure rate is equal to the acceptable failure rate. When the curve has a negative slope, the observed failure rate is lower than the acceptable failure rate. We performed a cumulative sum analysis of the first 97 intraoperative cholangiograms attempted during laparoscopic cholecystectomy at our institution. The results demonstrated that 46 cases were required to reach a level of proficiency where a cholangiogram could be obtained in 95% of attempts. Success rates of 85% and 90% were achieved at 16 and 25 cases, respectively. This form of analysis is a useful tool for estimating the number of attempts required to achieve a desired success rate when learning new procedures. Presented at the Thirty-Ninth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, La., May 17–20, 1998 (poster presentation).     

Biomechenical influence of the different attachments on implant-retained overdentures

目的：评价使用杆式、球形和磁性附着体对种植体支持式下颌覆盖义齿及其种植体的生物力学影响。方法：将两颗种植体代用品植入丙烯酸酯无牙颌模型的双侧尖牙区,在覆盖义齿的基托上粘附４ 块微型应变片,测量分析无附着体,杆式附着体和球形附着体覆盖义齿在４种力加载,５ 种力加载方向条件下的综合应变。结果：覆盖义齿变形在中线处最明显,球形附着体覆盖义齿与无附着体覆盖义齿的应变型相似,综合分析受力发生的应变与分别分析的结果基本一致。结论：杆式附着体覆盖义齿对种植体施加较大的水平力;球形附着体的覆盖义齿更符合粘膜和种植体共同支持牙合力的观点;磁性附着体覆盖义齿能吸收较多的水平分力。     

Mucosal production of complement C3 and serum amyloid A is differentially regulated in different parts of the gastrointestinal tract during endotoxemia in mice

The effect of endotoxemia and sepsis on mucosal production of the acute-phase proteins complement component C3 and serum amyloid A (SAA) was studied in mice. In addition, the role of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin (EL)-Iβ, and IL-6 on mucosal C3 and SAA production was examined. Endotoxemia was induced by the subcutaneous injection of 250 μg/mouse of lipopolysaccharide. Control mice were injected with corresponding volumes of sterile saline solution. Sepsis was induced by cecal ligation and puncture, and sham-operated mice served as controls. Endotoxemia resulted in increased mucosal C3 levels in all parts of the gastrointestinal tract examined, from the stomach to the colon, with the most pronounced effects noticed in the proximal gastrointestinal tract. The influence of endotoxemia on mucosal SAA production was more differentiated with increased levels noted in the jejunum and ileum, and no changes seen in gastric and colonic mucosa. Sepsis resulted in similar changes in mucosal C3 and SAA levels as seen in endotoxemic mice, except that SAA levels were increased in colonic mucosa of septic mice. Among the cytokines, IL-lβ resulted in the most pronounced changes in mucosal acute-phase proteins. The increase in C3 and SAA levels in the mucosa of the small intestine during endotoxemia was partially blocked by IL-1 receptor antagonist. The results suggest that endotoxemia is associated with increased mucosal C3 production in different parts of the gastrointestinal tract and increased SAA production in the mucosa of the small intestine. Mucosal acute-phase protein synthesis may, at least in part, be regulated by IL-1 β. Supported by a grant from the Shriners of North America. Some of the results reported herein were presented at the Thirty-Eighth Annual Meeting of The Society for Surgery of the Alimentary Tract, Washington, D.C., May 11–14, 1997.     

A fifteen-year follow-up of neurological conditions in VLBW children without overt disability: relation to gender, neonatal risk factors, and end stage MRI findings

BACKGROUND: Very low birthweight (VLBW; birthweight 相似文献   

Academic achievement, behavioural outcomes and MRI findings at 15 years of age in very low birthweight children

Abstract Aim: To assess cognitive, academic and behavioural functions in 15-year-old very low birthweight (VLBW) children and relate results to gender, neonatal risk factors, growth and magnetic resonance imaging (MRI) findings. Methods: Sixty-one out of 86 VLBW children and 57/86 term controls born in the south-east region of Sweden were assessed regarding cognition (WISC III), school outcome, behaviour and growth. VLBW children were examined using cerebral MRI. Results: VLBW children performed significantly lower than their term controls on WISC III and 49% had IQ lower than 85. Ten VLBW children with IQ < 70 had not been clinically identified earlier and a majority of these children attended mainstream school. VLBW girls had significantly lower total problems scores. Using MRI, white matter damage (WMD) was detected in 16 (27%) children. VLBW boys with WMD had significantly lower IQ than those without. Small occipito-frontal circumference (OFC) correlated with low IQ. Mechanical ventilation and intraventricular haemorrhage (IVH) showed significant correlations with lower IQ and reading skills. Conclusion: VLBW children achieved poorer results compared with their controls in cognitive tests. Mechanical ventilation and IVH were related to poorer academic outcome. Many of the children with low IQ had not been identified earlier. Therefore, we recommend that VLBW children undergo an IQ test before beginning school in order to receive adequate support.