Studies on the contact system of coagulation during therapy with high doses of recombinant IL-2: implications for septic shock

Patients treated with high doses of interleukin-2 (IL-2) because of cancer, develop hemodynamic and vasopermeability changes, that resemble those observed in sepsis. These patients thus provide a unique opportunity to study the early events in the development of septic shock. We analysed the changes that occurred in the contact system of coagulation in plasma from 4 patients, who together received seven 12-day cycles of high doses of IL-2. Levels of factor XII and prekallikrein during the cycles progressively fell to 50 and 30% of their initial levels, respectively, whereas significant increases in plasma factor XIIa- and kallikrein-C1-inhibitor complexes were not observed (in 3 out of 211 samples slightly increased levels of both complexes were found). The reductions in factor XII and prekallikrein were only in part due to protein leakage, since levels were still significantly lower, i.e., 80 and 50%, respectively, when corrected for albumin decreases. Levels of high molecular weight kininogen (HMWK) also decreased during IL-2 therapy, however, this decrease paralleled that of albumin. SDS-PAGE analysis of plasma HMWK did not reveal increased cleavage of this protein. The reduction of factor XII and prekallikrein, corrected for protein leakage, significantly correlated with albumin levels and inversely with daily cumulative weight gain in the patients. Thus, we demonstrate that factor XII and prekallikrein decrease during IL-2 therapy. As these decreases, already observed after 1 day treatment, were disproportional to that of albumin, a negative acute phase reactant, and correlated with signs of the vascular leak syndrome, we favor the explanation that they reflected activation rather than a decreased synthesis of the contact system proteins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Legume intake and gallstone risk: results from a case-control study

As legume intake was recently shown to increase biliary cholesterol saturation, it may be a risk factor for gallstone disease. Data from a case-control study in The Netherlands were analysed to confirm this hypothesis. A negative association was found between legume intake (including green beans) and gallstone risk. This appeared not to be explained by diminished legume intake in gallstone cases under the influence of gastrointestinal symptoms. We hypothesize that components from legume pulses (seeds) and pods may have opposite effects on the risk of gallstone development.     

An enzyme-linked immunosorbent assay (ELISA) for the measurement of antibodies to different parts of the gram-negative lipopolysaccharide core region

Bovine serum albumin was complexed with the core antigens of either Escherichia coli J5 LPS, Salmonella minnesota R595 LPS or E. coli lipid A. These core-BSA complexes were used for solid-phase coating in ELISAs for anti-core antibodies. Antibodies, binding to various parts of the core region were easily quantified in a single experimental set-up, which was hitherto not possible. The ELISA has only 3 incubation steps and is not costly as only moderate amounts of the core antigens (i.e., 1 microgram per test) were needed for coating. The sensitivity proved to be excellent and the complexes were biologically fully active (compared to native, smooth LPS), which make them suitable for the screening (after fusion) of monoclonal anti-core antibodies. Another possible application is the large-scale screening of blood-bank sera in order to find samples with a high anti-core antibody content.     

The Impact of Pre-exposure Prophylaxis on Sexual Well-Being Among Men Who Have Sex with Men

Archives of Sexual Behavior - Pre-exposure prophylaxis (PrEP) is a promising strategy to reduce HIV incidence among men who have sex with men (MSM). How and when PrEP is used could in part be...     

Diffusion-weighted MR imaging in acute ischemia: value of apparent diffusion coefficient and signal intensity thresholds in predicting tissue at risk and final infarct size

BACKGROUND AND PURPOSE: Identifying tissue at risk for infarction is an important goal of stroke imaging. This study was performed to determine whether pixel-based apparent diffusion coefficient (ADC) and signal intensity ratio are helpful diffusion-weighted (DW) imaging metrics to predict tissue at risk for infarction. METHODS: Twelve patients presenting with acute hemispheric strokes underwent DW imaging within 7 hours of symptom onset. Region of interest (ROI), pixel-based ADC, and signal intensity analyses were performed at initial DW imaging to assess area of infarct growth, final infarct area, and normal tissue. RESULTS: Pixel-based analysis was less accurate than ROI-based analysis for evaluating infarct growth or final infarct with ADC, ADC ratio, and signal intensity ratios. In pixel-based analysis, signal intensity ratios were better than ADCs or ADC ratios for identifying tissue at risk (accuracy, 67.4%) and for predicting final infarct (accuracy, 79.9%). Linear regression analysis demonstrated a strong correlation between lesion volume on quantitative DW images or ADC maps and final infarct volume (P < .001). When receiver operating characteristic (ROC) curves were used to determine optimal cutoffs for ADC and DW image values, the region of infarct growth was significantly correlated with only the mismatch between initial qualitative DW image and quantitative DW image signal intensity ratio (cutoff value, 1.19; R = 0.652; P = .022). CONCLUSION: Pixel-based thresholds applied to ADC or DW image signal intensity maps were not accurate prognostic measures of tissue at risk. Quantitative DW images or ADC maps may provide added information not obtained by visual inspection of the qualitative DW image map.     

Anemia and blood transfusion in critically ill patients

Context  Anemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the critically ill is poorly defined. Objectives  To prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU. Design  Prospective observational study conducted November 1999, with 2 components: a blood sampling study and an anemia and blood transfusion study. Setting and Patients  The blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death. Main Outcome Measures  Frequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period. Results  The mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r = 0.34; P<.001) and total volume drawn (r = 0.28; P<.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; ² = 50.1; P<.001; overall rates: 29.0% vs 14.9%, respectively; ² = 88.1; P<.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P = .02); the Kaplan-Meier log-rank test confirmed this difference. Conclusions  This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.      

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.