Organ failure and tight glycemic control in the SPRINT study

Introduction  

Intensive care unit mortality is strongly associated with organ failure rate and severity. The sequential organ failure assessment (SOFA) score is used to evaluate the impact of a successful tight glycemic control (TGC) intervention (SPRINT) on organ failure, morbidity, and thus mortality.     

Low subcutaneous degradation and slow absorption of insulin in insulin-dependent diabetic patients during continuous subcutaneous insulin infusion at basal rate

Summary As information on the absorption kinetics and local degradation of infused insulin is relevant to programming strategies for continuous subcutaneous insulin infusion, we examined the time relationship of systemic insulin appearance and quantitated subcutaneous degradation during a near-basal rate of continuous subcutaneous insulin infusion in five insulin-dependent diabetic patients. Plasma free insulin was monitored for 8 h during and 3 h after a subcutaneous (abdominal wall) infusion of neutral insulin at 2.4 U/h. An identical intravenous infusion (2–4 h) was given on a separate occasion. Plateau levels of free insulin were not significantly different during the subcutaneous (37±8 mU/l) and intravenous (40±7 mU/l) infusions. Fitting of the free insulin data to our two-pool model of the subcutaneous space gave a mean estimate of 9.2 units insulin (= 3.8 h infusion) for the subcutaneous depot after 8 h. Model estimates of systemic insulin appearance, as a percentage of subcutaneous infusion rate, were 59% and 93% after 4 and 8 h respectively, and 76% 2 h after cessation of infusion. In insulin-dependent diabetic patients subcutaneous degradation of infused insulin is negligible but local accumulation in the subcutaneous space is considerable. The delay in absorption has important clinical implications for interruption and resumption of continuous subcutaneous insulin infusion and also for programming of variable basal rates.     

Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

Effect of Port Composition on Tumor Cell Adherence

INTRODUCTION: We have reported previously on an in vitro model to examine tumor cell adherence to metal and plastic laparoscopic ports and to port sites through which they had been passed. This demonstrated that increased numbers of tumor cells were found both on metal ports compared with plastic ports and on the port sites through which metal ports had passed. In this study, the in vivo adherence of such cells to ports and port sites was investigated. METHODS: LIM 1215 tumor cells were injected under direct vision into the pelvises of 16 30-kg female pigs (range, 15–70 × 106 cells). A total of 12 ports were inserted through each anterior abdominal wall (6 metal and 6 plastic), and these were either left in situ for 30 minutes (nondisplaced) or were removed twice and replaced through the original wound (displaced). RESULTS: Increasing the tumor cell inoculum resulted in increased deposition of tumor cells on both ports (P = 0.002) and on the port sites (P = 0.017). Significantly more tumor cells adhered to metal ports than to plastic ports (P = 0.04), although this failed to reach significance for the sites through which metal ports had been passed (P = 0.066). Although displacement of ports did not increase the number of tumor cells that adhered to ports (P = 0.45), this did result in more tumor cells being deposited on the port sites (P = 0.01). CONCLUSIONS: These data suggest that minimizing the number of tumor cells within the abdominal cavity, using plastic ports, and securing ports to prevent inadvertent displacement would be expected to reduce the number of tumor cells deposited in port sites during operative laparoscopy. This may be beneficial in reducing the incidence of port-site metastases after laparoscopic surgery for gastrointestinal malignancies.     

Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4

Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors.     

Pain in rheumatoid arthritis: relationship to demographic, medical, and psychological factors

Our purpose was to investigate the relationship among demographic, medical, and psychological factors and self-reported pain in 135 patients with classic or definite rheumatoid arthritis (RA). Patients were examined using the systemic index, articular index, McGill Pain Questionnaire, Symptom Checklist-90-R, and a pain visual analogue scale. Multiple regression analyses found no significant relationships between pain and the medical variables. However, age, income, and selected psychological variables were significantly correlated with pain reports. The greatest pain management challenge occurred in patients who were middle-aged, living on limited incomes, and experiencing major stresses in everyday life. These high risk pain patients were also worry-prone and felt isolated and lacking in social support. Attention to these related psychosocial problems is recommended as an important pain management strategy in RA.