Adult respiratory distress syndrome. Prognosis after onset

In 88 patients with the adult respiratory distress syndrome, clinical, laboratory, cardiopulmonary, and demographic data collected on the day of onset of the syndrome were used to identify predictors of survivorship and mortality. Variables that individually were associated with mortality were then analyzed simultaneously by the Cox proportional hazards function and by multiple discriminant function using a step-up procedure. Four variables taken singly were significantly associated with mortality. These were the presence of less than 10% band forms on the initial peripheral blood smear, persistent acidemia with arterial pH less than 7.40, calculated HCO-3 less than 20 mg/dl, and blood urea nitrogen greater than 65 mg/dl. After eliminating those variables that did not contribute significantly to mortality in the presence of the others, only low band forms, low pH, and low HCO-3 were significantly associated with increased mortality. These findings illustrate the continued high mortality rate in the syndrome and indicate possible systemic aberrations that contribute to its severity.     

Inhibition of the intrinsic factor X activating complex by protein S: evidence for a specific binding of protein S to factor VIII

Protein S is a vitamin K-dependent nonenzymatic anticoagulant protein that acts as a cofactor to activated protein C. Recently it was shown that protein S inhibits the prothrombinase reaction independent of activated protein C. In this study, we show that protein S can also inhibit the intrinsic factor X activation via a specific interaction with factor VIII. In the presence of endothelial cells, the intrinsic activation of factor X was inhibited by protein S with an IC50 value of 0.28 +/- 0.04 mumol/L corresponding to the plasma concentration of protein S. This inhibitory effect was even more pronounced when the intrinsic factor X activation was studied in the presence of activated platelets (IC50 = 0.15 +/- 0.02 mumol/L). When a nonlimiting concentration of phospholipid vesicles was used, the plasma concentration of protein S (300 nmol/L) inhibited the intrinsic factor X activation by 40%. Thrombin-cleaved protein S inhibited the endothelial cell-mediated factor X activation with an IC50 similar to that of native protein S (0.26 +/- 0.02 mumol/L). Protein S in complex with C4b-binding protein inhibited the endothelial cell-mediated factor X activation more potently than protein S alone (IC50 = 0.19 +/- 0.03 mumol/L). Using thrombin activated factor VIII, IC50 values of 0.53 +/- 0.09 mumol/L and 0.46 +/- 0.10 mumol/L were found for native protein S and thrombin-cleaved protein S, respectively. The possible interactions of protein S with factor IXa, phospholipids, and factor VIII were investigated. The enzymatic activity of factor IXa was not affected by protein S, and interaction of protein S with the phospholipid surface could not fully explain the inhibitory effect of protein S on the factor X activation. Using a solid-phase binding assay, we showed a specific, saturable, and reversible binding of protein S to factor VIII with a high affinity. The concentration of protein S where half-maximal binding was reached (B1/2max) was 0.41 +/- 0.06 mumol/L. A similar affinity was found for the interaction of thrombin-cleaved protein S with factor VIII (B1/2max = 0.40 +/- 0.04 mumol/L). The affinity of the complex protein S with C4B-binding protein appeared to be five times higher (B1/2max = 0.07 +/- 0.03 mumol/L). Because the affinities of the interaction of the different forms of protein S with factor VIII correspond to the IC50 values observed for the intrinsic factor X activating complex, the interaction of protein S with factor VIII may explain the inhibitory effect of protein S on the intrinsic factor X activating complex.(ABSTRACT TRUNCATED AT 400 WORDS)     

Heparin therapy. Regimens and treatment considerations.

Heparin is a parenteral antithrombotic agent with efficacy in the treatment and prevention of venous thromboembolic disease and in preinfarctional angina. Accumulating evidence also suggests that heparin is useful in the prevention of coronary artery reocclusion after thrombolytic therapy for acute myocardial infarction, and in the prevention of left ventricular mural thrombosis after anterior wall myocardial infarction. Heparin appears to offer only marginal benefit in reducing mortality when given in combination with thrombolytic therapy and aspirin for acute myocardial infarction. When used for prevention of venous thromboembolism in moderate risk patients, heparin should be given subcutaneously in a dose of 5000 U every 12 hours for 5 to 7 days or until the patient is ambulatory. In higher risk patients, such as those undergoing total hip replacement, heparin should be given subcutaneously every 12 hours in a dose to prolong the activated partial thromboplastin time (aPTT) by 4 to 5 seconds into the upper normal range. When used to treat active venous thromboembolism or the peri-infarctional state, heparin should be given by intravenous infusion with loading and maintenance doses to consistently prolong the aPTT to between 1.5- and 2.5-fold the control value (mean of laboratory's normal range). If constant intravenous infusion is not possible, the drug should be given subcutaneously every 12 hours to consistently prolong the aPTT between 1.5 and 2.5 times control. This regimen is also recommended in pregnant women with venous thromboembolic disease or mechanical heart valves.     

Multi-quadrant biopsy technique improves diagnostic ability in large heterogeneous renal masses. Abel EJ,Heckman JE,Hinshaw L,Best S,Lubner M,Jarrard DF,Downs TM,Nakada SY,Lee FT Jr,Huang W,Ziemlewicz T.J Urol. 2015 Oct;194(4):886-91. [Epub 2015 Mar 30]. doi: 10.1016/j.juro.2015.03.106.

Purpose

Percutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to nondiagnostic results or failure to detect poor prognostic features. We evaluated the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique vs. a standard biopsy technique.

Actinic keratosis: an occupational and environmental disorder

Solar ultraviolet light electromagnetic waves are a known environmental carcinogenic agent closely associated with the development of skin cancer in light‐complexioned individuals. Outdoor workers have higher annual exposure to ultraviolet light. We will review the topic of actinic keratoses among these individuals as this common rudimentary form of superficial cutaneous squamous cell carcinoma is explored in greater detail.