Platelet decline is a feature of many acute viral infections, including cytomegalovirus (CMV) infection in humans and mice. Platelet sequestration in association with other cells, including ...endothelium and circulating leukocytes, can contribute to this decline and influence the immune response to and pathogenesis of viral infection. We sought to determine if platelet-endothelial associations (PEAs) contribute to platelet decline during acute murine CMV (mCMV) infection, and if these associations affect viral load and production. Male BALB/c mice were infected with mCMV (Smith strain), euthanized at timepoints throughout acute infection and compared to uninfected controls. An increase in PEA formation was confirmed in the salivary gland at all post-inoculation timepoints using immunohistochemistry for CD41+ platelets co-localizing with CD34+ vessels. Platelet depletion did not change amount of viral DNA or timecourse of infection, as measured by qPCR. However, platelet depletion reduced viral titer of mCMV in the salivary glands while undepleted controls demonstrated robust replication in the tissue by plaque assay. Thus, platelet associations with endothelium may enhance the ability of mCMV to replicate within the salivary gland. Further work is needed to determine the mechanisms behind this effect and if pharmacologic inhibition of PEAs may reduce CMV production in acutely infected patients.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The American College of Surgeons (ACS) recommends trauma overtriage rate (OT) below 50 per cent to maximize efficiency while ensuring optimal care. This retrospective study was undertaken to evaluate ...OT rates in our Level I trauma center using the most recent criteria and guidelines. OT rates during a 12-month period were measured using six definitions based on combinations of Injury Severity Score (ISS), length of hospital stay (LOS, in days), procedures, and disposition after the emergency department. Reason for trauma activation was 55 per cent criteria, 16 per cent guidelines, 11 per cent paramedic judgment, five per cent no reason, and 13 per cent no documentation. OT rates ranged from 22.6 per cent (ISS less than 9, LOS 1 day or less, no consults) to 48.2 per cent (ISS less than 9, LOS 3 days or less, with procedures/consults) and were in compliance with ACS recommendations. Physiologic assessment criteria and anatomic injury had the lowest OT rates and contained all mortalities. Passenger space intrusion (PSI), pedestrian versus automobile (criterion and guideline), and extrication (guideline) all had consistently high rates of OT. We conclude that PSI should be reduced to a guideline, the pedestrian versus automobile criterion and guideline should be combined, and extrication could be removed from the triage scheme.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
BACKGROUND:Fasting hyperglycemia has been associated with HIV protease inhibitor (PI) therapy.
OBJECTIVE:To determine whether absolute insulin deficiency or insulin resistance with relative insulin ...deficiency and an elevated body mass index (BMI) contribute to HIV PI-associated diabetes.
DESIGN:Cross-sectional evaluation.
PATIENTS:8 healthy seronegative men, 10 nondiabetic HIV-positive patients naive to PI, 15 nondiabetic HIV-positive patients receiving PI (BMI = 26 kg/m), 6 nondiabetic HIV-positive patients receiving PI (BMI = 31 kg/m), and 8 HIV-positive patients with diabetes receiving PI (BMI = 34 kg/m). All patients on PI received indinavir.
MEASUREMENTS:Fasting concentrations of glucoregulatory hormones. Direct effects of indinavir (20 μM) on rat pancreatic β-cell function in vitro.
RESULTS:In hyperglycemic HIV-positive subjects, circulating concentrations of insulin, C-peptide, proinsulin, glucagon, and the proinsulin/insulin ratio were increased when compared with those of the other 4 groups (p < .05). Morning fasting serum Cortisol concentrations were not different among the 5 groups. Glutamic acid decarboxylase (GAD) antibody titers were uncommon in all groups. High BMI was not always associated with diabetes. In vitro, indinavir did not inhibit proinsulin to insulin conversion or impair glucose-induced secretion of insulin and C-peptide from rat β-cells.
CONCLUSIONS:The pathogenesis of HIV PI-associated diabetes involves peripheral insulin resistance with insulin deficiency relative to hyperglucagonemia and a high BMI. Pancreatic β-cell function was not impaired by indinavir. HIV PI-associated diabetes mirrors that of non-insulin-dependent diabetes mellitus and impaired insulin action in the periphery.
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