Low revascularization of experimentally transplanted human pancreatic islets

Pancreatic islets are avascular immediately after transplantation. Although the islets are rapidly revascularized, it is uncertain whether the revascularization produces an adequate oxygenation of the transplanted islet tissue. We measured pO(2), blood flow and vascular density in mouse or human islets 1 month after transplantation to nude mice. Tissue pO(2) was measured with Clark microelectrodes. Blood perfusion was measured with laser-Doppler flow cytometry, whereas vascular density was determined in histological specimens stained for the lectin Bandeiraea simplicifolia (BS-1). Both the transplanted mouse and human islets had a pO(2) 15-20% of that in endogenous mouse islets. Moreover, the vascular density of the transplanted islets was decreased compared with that of endogenous mouse and human islets. Graft blood perfusion was approximately 50% of renal cortex blood flow. A negative correlation was found between donor age and blood perfusion of the human islet grafts. A similar correlation was seen between donor age and the total vascular density of these grafts. In conclusion, transplanted human islets had a markedly decreased vascular density and pO(2) compared with endogenous islets. This has potential implications for clinical islet transplantations, because poor vascular engraftment may significantly increase the number of islets needed to obtain insulin independence.     

Distribution of intraportally implanted microspheres and fluorescent islets in mice

The aim of the study was to evaluate the distribution of intraportally transplanted islets in mice. We initially administered 2000 polystyrene microspheres with a diameter of 50 microm intraportally into normoglycemic C57BL/6 mice. In separate experiments other mice were injected similarly with 300 microspheres each with a diameter of 100 or 200 microm. One week later the animals were killed, and the lungs and livers were removed and divided into lobes. The number of microspheres in each individual liver lobe and in the lungs was counted using a stereomicroscope. In other experiments, athymic C57BL/6 mice were similarly implanted with 250 islets isolated from transgenic mice expressing the enhanced yellow fluorescent protein in the islet cells. The distribution of microspheres and islets was independent of size, and fairly homogenous within the liver, with the exception of the caudate lobe, which contained fewer microspheres and islets, respectively. Approximately one third of all microspheres and islets were present as aggregates. Eighty-five to 90% of the implanted microspheres were identified in the liver sections, whereas 60-65% of the implanted islets were recovered. Aggregates or single fluorescent cells were observed in the liver of islet-implanted mice. We conclude that islets and microspheres implanted into the liver distribute fairly homogenously and quite a few of them exist as aggregates or, with respect to islets, as fragments.     

Influence of optimised treatment of people with hip fracture on time to operation, length of hospital stay, reoperations and mortality within 1 year

Hip fractures are a major cause of hospital stay among the elderly, and result in increased disability and mortality. In this study from 1 April 2003 to 31 March 2004, the influence of optimised treatment of hip fracture on time to operation, length of hospital stay, reoperations and mortality within 1 year were investigated. Comparisons were made between the first 210 patients in the period and the last 210 patients, who followed the new clinical pathway introduced at the University Hospital in Lund, Sweden. Early surgery, within 24 h, was not associated with reduced mortality, but was significantly associated with reduced length of stay (p < 0.001). Significantly more cases of osteosynthesis for femoral neck fracture were reoperated compared with all other types of surgery (p < 0.001) when reoperations with extraction of the hook pins in healed fractures were excluded. Mortality was significantly higher among men than women at 4 (p = 0.025) and 12 (p = 0.001) months after fracture and among medically fit patients with administrative delay to surgery compared with patients with no delay (p < 0.001).     

Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma

The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.     

Evaluation of clinical staging in chronic lymphocytic leukemia- population-based study

The Rai and Binet staging systems are currently being challenged by the development of new biological methods to characterize the prognosis and management of chronic lymphocytic leukemia (CLL). To evaluate these two systems in recently diagnosed CLL patients, we performed a retrospective population-based study including 344 patients in western Sweden diagnosed between 1995 and 2000. Binet stage A patients had longer median overall survival (OS) (100 months) than stage B (55 months; P < 0.001) and C patients (45 months; P < 0.0005). Median OS for stage B and C could not be separated (P = 0.94). When transferring Rai stages into three groups, a similar pattern was found. Overall response differed only between Binet A and C patients and there was no difference regarding time to next treatment between any of the Binet stages. Finally, in both systems, low stage patients had inferior survival compared to age- and sex-matched controls. Our data emphasize the need for a new risk stratification system for CLL patients.     

Adenosine A1 receptors in contrast media-induced renal dysfunction in the normal rat

Renal vasoconstriction with resultant tissue hypoxia, especially in the renal medulla, has been suggested to play a role in contrast media (CM)-induced nephropathy. In this study we investigated the effects of injection of the non-ionic low-osmolar CM iopromide with and without pretreatment with the selective adenosine A₁-receptor antagonist DPCPX. The effects were evaluated on regional renal blood flow, outer medullary oxygen tension (PO₂) and urine output in normal anaesthetised rats. A laser-Doppler technique was used for recording haemodynamic changes while oxygen microelectrodes were used for oxygen measurements. The A₁-receptor antagonist per se elevated glomerular filtration rate (+44%), cortical blood flow (+15%) and urine output (threefold) while reducing outer medullary PO₂ (–24%). Administration of CM reduced outer medullary blood flow (OMBF; –26%) and PO₂ (–80%) but did not affect cortical blood flow. Urine output increased 28-fold by CM while arterial blood pressure was reduced. The CM-mediated effect on haemodynamics, PO₂, urine output and blood pressure was unaffected by the A₁-receptor antagonist. Adenosine A₁-receptors are not important mediators of the depression of outer medullary blood flow and PO₂ caused by the CM iopromide in the normal rat; however, A₁-receptors are tonically active to regulate renal haemodynamics, PO₂ and urine production during normal physiological conditions.     

A through-the-scope device for suturing and tissue approximation under EUS control

BACKGROUND: The ability to place sutures under EUS control might allow development of a new type of transluminal endosurgery. The aim of this study was to develop endoscopic methods for suturing to variable predetermined depths in the wall of the GI tract and to allow fixation of adjacent hollow organs under EUS control. METHODS: A suturing device was constructed for suturing under EUS control to any desired depth. Sutures can also be placed into hollow or solid organs within 5 cm of the endoscope tip. The device allows multiple sutures to be placed without withdrawing the endoscope. Stitching, knot-tying, and thread-cutting are achieved through a 2.8-mm accessory channel. RESULTS: Multiple (>100) sutures were placed in predetermined gut wall layers in pigs. Sutures were placed in the gallbladder (n = 7) and small intestine (n = 8) to fix the gallbladder/small intestine to the stomach and allow traction for the insertion of stents and other devices through the 2 lumens. CONCLUSION: A new method for stitching under flexible EUS control is described. This technology was used to place sutures at precise depths in the GI tract. It allowed fixation of other organs to the accessible GI tract for various purposes including delivery of stents and devices for creating anastomoses.     

Prevention of clot formation during haemodialysis using the direct thrombin inhibitor melagatran in patients with chronic uraemia

Sir, We have read the editorial comment by MJ Flanigan [1] on ourrecent study ‘Prevention of clot formation during haemodialysis