HELLP syndrome associated with factor V R506Q mutation

The pathogenesis of HELLP (haemolysis, elevated liver enzyme and low platelet count) syndrome, a severe presentation of pre-eclampsia, is still an enigma. Activated protein C resistance resulting from a mutation in coagulation factor V has recently emerged as the leading cause of thrombosis in pregnancy. We report on two patients with HELLP syndrome who were found to be heterozygous for factor V R506Q mutation, leading to activated protein C resistance. These findings suggest that the pathogenesis of HELLP syndrome is associated with a thrombotic process, and point to the potential benefit of anti-thrombotic therapy in this condition.     

Use of current situational information and causal inference: Do dysphoric individuals make “unwarranted” causal inferences?

According to Beck's original theory, depressives make unwarranted negatively biased personal inferences. Specifically, Beck suggested that depressives ignore current positive situational information and are unduly influenced by current negative situational information in making inferences. To test Beck's theory, we used Kelley's normative model of causal inference to examine the utilization of causally relevant situational information by dysphoric, nondepressed, and very nondepressed subjects in making causal attributions for personal success and failure. We used Stevens and Jones' classic method from social psychology and embedded the relevant causal information in the natural flow of events. Results showed that dysphoric, nondepressed, and very nondepressed subjects did, to an equal degree, use such information to make causal attributions. Although dysphoric and both groups of nondepressed subjects used current situational information consistently with Kelley's model, clear-cut baseline differences in the content of their causal attributions existed. Thus, the results supported the reformulations of Beck's theory that emphasize content, rather than process, differences between depressive and nondepressive cognition for dysphoria.Preparation of this article was supported by a Vilas Award, a University of Wisconsin Graduate School Grant, a Romnes Fellowship, a Biomedical Grant, and NIMH Grant R01MH43866 to Lyn Y. Abramson.     

The effect of endothelium-derived nitric oxide on ex vivo whole blood platelet aggregation in man

Summary The effects of changes in endogenous endothelium-derived nitric oxide (NO) on forearm blood flow and ex vivo platelet aggregation have been studied in 7 healthy volunteers.Measurements were made of forearm blood flow and ex vivo collagen-stimulated platelet aggregation during unilateral brachial artery infusions of saline, acetylcholine (ACh), N^G monomethyl-L-arginine (L-NMMA), and prostacyclin (PGI₂). The uninfused arm acted as a control.Forearm blood flow was increased by ACh, an agent which stimulates NO release, and decreased by L-NMMA, an agent which stereospecifically inhibits NO synthesis.Collagen-stimulated platelet aggregation measured ex vivo in whole blood draining the infused arm was unaltered by either ACh or L-NMMA. Conversely, PGI₂, an agent which acts independently of NO, caused an increase in forearm blood flow which was accompanied by significant inhibition of platelet aggregation.The results suggest that release of endothelium-derived NO in quantities sufficient to cause substantial changes in blood vessel tone does not lead to changes in platelet aggregation in the blood flowing through the vessels. It is, however, still possible that endothelium-derived NO modulates platelet activity at the level of the endothelium. Present address: Department of Medicine and Therapeutics, University of Aberdeen Polwarth Building, Forrester Hill, Aberdeen, UK     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

A method for partitioning cancer mortality trends by factors associated with diagnosis: An application to female breat cancer

U.S. cancer mortality data derived from information recorded on death certificates are frequently relied upon as an indicator of progress against cancer. A limitation of this measure is the lack of information pertaining to the onset of disease, such as year-of-diagnosis, age-at-diagnosis, stage of disease at diagnosis and histology of lesions. However, population-based cancer registries collect these types of data and allow the calculation of an incidence-file based mortality rate. This incidence-based mortality rate allows a partitioning of mortality by variables associated with the cancer onset. Breast cancer incidence-based mortality measures are created and compared to mortality rates based on death certificates over a comparable time period. Novel mortality measures, such as mortality rates by stage-at-diagnosis, age-at-diagnosis and year-of-diagnosis, are used to illustrate the value of this approach.     

Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4

Interleukin (IL)-2 and IL-4 are considered as important regulators of growth and differentiation of lymphocytes. We report that in mice made deficient for both IL-2 and IL-4 by gene targeting all major T cell subsets and B cells were normal, indicating that IL-2 and IL-4 are not essential for development of the immune system. Paradoxically, proliferation of T cells was increased in both IL-2- and IL-4-deficient homozygous mice.     

A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin.

OBJECTIVES: Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG. METHODS: A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20 ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000 mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion. RESULTS: Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642 mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates < or =1000 g and slightly higher in neonates 1001 to 1500 g. Trough levels before second infusion were 188 mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5 mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm. CONCLUSIONS: Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.