Assessment of human islet viability using various mouse models.

To date no in vitro viability test is known to accurately predict in vivo human islet function, making transplantation into various nonimmune animal models mandatory. The diabetic mouse model has been proposed as a standard method for human islet viability assessment. However, the use of streptozotocin for diabetes induction is associated with inconsistency with respect to induction protocols and the significant mortality rate. The purpose of this study was to compare a nondiabetic NOD-scid mouse model to its diabetic counterpart in terms of predicting islet viability. Diabetes was induced in NOD-scid mice using intraperitoneal injection of streptozotocin at concentrations ranging from 100 to 200 mg/kg. Blood glucose levels were monitored for 7 to 10 days, and mice that had levels of >300 mg/dL were used in the experiment. For nondiabetic mice, blood glucose and baseline human C-peptide levels were checked after an overnight fast. Transplantation of 2000 human islet equivalent was done in both models using the same technique. Islet function was determined in the diabetic mice by return to normoglycemia for 2 consecutive days and measurement of fasting human C-peptide on days 7 and 14 posttransplant. Viability was tested in nondiabetic mice after intraperitoneal injection of glucose (2 g/kg) and the measurement of human C-peptide levels using radioimmunoassay. Titration of the streptozotocin dose from 200 to 100 mg/kg showed a significant reduction in mice mortality (40% to 10%) and an increase of diabetes induction (55% to 81%). The 23 human islet isolations tested in both models showed complete consistency of the viability results.

Discharge planning from hospital to home.

BACKGROUND: Discharge planning is a routine feature of health systems in many countries. The aim is to reduce hospital length of stay and unplanned readmission to hospital, and improve the co ordination of services following discharge from hospital thereby bridging the gap between hospital and place of discharge. Sometimes discharge planning is offered as part of an integrated package of care, which may cover both the hospital and community. The focus of this review is discharge planning that occurs while a patient is in hospital; we exclude studies that evaluate discharge planning with follow up care. OBJECTIVES: To determine the effectiveness of planning the discharge of patients moving from hospital. SEARCH STRATEGY: Relevant studies were identified using Medline, Embase, SIGLE database for grey literature, Bioethics database, Health Plan, Psych. Lit, Sociofile, CINAHL, Cochrane Library, Econ Lit, Social Science Citation Index, EPOC register. The review was updated using the EPOC trials register in August 2002. STUDY DESIGN: randomised controlled trials (RCTs) that compare discharge planning (the development of an individualised discharge plan) with routine discharge care. PARTICIPANTS: all patients in hospital. INTERVENTION: the development of an individualised discharge plan. DATA COLLECTION AND ANALYSIS: Data analysis and quality assessment was undertaken independently by two reviewers using a data checklist. Studies are grouped according to patient group (elderly medical patients, surgical patients, and those with a mix of conditions), and by outcome. MAIN RESULTS: Three new studies were included in this update. In total we included eleven RCTS: 6 trials recruited patients with a medical condition (2,368 patients), and four recruited patients with a mix of medical and surgical conditions (2,983 patients), one of these four recruited medical and surgical patients as separate groups, and the final trial recruited 97 patients in a psychiatric hospital and from a general hospital. We failed to detect a difference between groups in mortality for elderly patients with a medical condition (OR 1.44 95% CI 0.82 to 2.51), hospital length of stay (weighted mean difference -0.86, 95% CI -1.9 to 0.18), readmission rates (OR 0.91 95% CI 0.67 to 1.23) and being discharged from hospital to home (OR 1.15 95% CI 0.72 to 1.82). This was also the case for trials recruiting patients recovering from surgery and those recruiting patients with a mix of medical and surgical conditions. One trial comparing a structured care pathway for patients recovering from a stroke with multidisciplinary care reported a significant rate of improvement in functional ability and quality of life for the control group (median change in Barthel score between 4 to 12 weeks of 2 points for the treatment group, versus 6 for the control group, p<0.01); (Euroqol scores at 6 months 63 for the treatment group, vs. 72 for the control group, p<0.005). Two trials reported that patients with medical conditions allocated to discharge planning reported increased satisfaction compared with those who received routine discharge. No statistically significant differences were reported for overall health care costs. REVIEWER'S CONCLUSIONS: The impact of discharge planning on readmission rates, hospital length of stay, health outcomes and cost is uncertain. This reflects a lack of power as the degree to which we could pool data was restricted by the different reported measures of outcome. It is possible that even a small reduction in length of stay, or readmission rate, could have an impact on the timeliness of subsequent admissions in a system where there is an shortage of acute hospital beds.

Dual blockade of P-selectin and beta2-integrin in the liver inflammatory response after uncontrolled hemorrhagic shock.

BACKGROUND: Neutrophil infiltration is a characteristic feature of the hepatic injury associated with prolonged hypotension. Previous work has already stressed the important contribution of neutrophil-endothelial cell interactions in the organ injury seen after hemorrhagic shock. Single-blockade strategies using monoclonal antibodies (MAbs) against either selectin or integrin receptors have been demonstrated to be effective in limiting the tissue inflammatory response observed in this clinical disorder. One unexplored topic is the additive effect(s) and the potential antiinflammatory properties of the combined blocking of P-selectin plus beta2-integrin in the liver inflammatory response after uncontrolled hemorrhagic shock in rats. STUDY DESIGN: Sprague-Dawley rats (n = 64) weighing 250-300 g were included in a three-phase model of uncontrolled hemorrhagic shock. A prehospital phase consisted of 90 minutes of fluid resuscitation with lactated Ringer's solution to reach a mean arterial pressure (MAP) of 40 mmHg; a hospital phase consisted of 60 minutes of hemostasis and fluid resuscitation with lactated Ringer's solution to reach a MAP of 80 mmHg; and the third phase was 3 days of observation. All rats had 3 mL/100 g of blood volume shed during the initial 15 minutes. At 30 minutes, 75% tail amputation produced uncontrolled hemorrhagic shock. Four groups were randomized (n = 16 per group), and treatment at the beginning of resuscitation included normal saline (group 1); anti-P-selectin MAb, RMP-1 (group 2); anti-beta2-integrin MAb, WT.3 (group 3); or anti-P-selectin plus anti-beta2-integrin MAbs (group 4). The following indices were evaluated: fluid requirements for resuscitation, liver injury tests, liver tissue myeloperoxidase, and liver histology. RESULTS: Dual blockade of P-selectin and beta2-integrin significantly reduced fluid requirements for resuscitation (p < 0.05). We also observed a statistically significant improvement (p < 0.05) in tests demonstrating hepatic injury, myeloperoxidase in hepatic tissue, and histology studies. Survival was increased from 40% in controls to 60% with the dual-blockade treatment. CONCLUSIONS: These results indicate that dual-blockade strategies aimed at P-selectin and beta-integrin provided a protective effect in the liver inflammatory response after uncontrolled hemorrhagic shock in rats. Although dual blockade was more effective than either individual blockade alone, questions remain about the possible redundancy in the inflammatory adhesion pathways after this clinical condition.