The in vivo kinetics of tissue factor messenger RNA expression during human endotoxemia: relationship with activation of coagulation

Triggering of the tissue factor (TF)-dependent coagulation pathway is considered to underlie the generation of a procoagulant state during endotoxemia. To determine the in vivo pattern of monocytic TF messenger RNA (mRNA) expression during endotoxemia, 10 healthy volunteers were injected with lipopolysaccharide (LPS, 4 ng/kg) and blood was collected before and 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after LPS administration. Total blood RNA was isolated and amplified by NASBA (nucleic acid sequence-based amplification), followed by quantitation of TF mRNA by an electrochemiluminescence (ECL) assay. To compare the pattern of coagulation activation with the kinetics of monocytic TF mRNA expression, we measured plasma levels of markers of thrombin generation, thrombin-antithrombin (TAT) complexes, and prothrombin fragment 1 + 2 (F1 + 2). Baseline value (mean +/- SEM) of the number of TF mRNA molecules per monocytic cell was 0.08 +/- 0.02. A progressive and significant (P <.0001) increase in TF expression was observed after LPS injection (+0.5 hour: 0.3 +/- 0.1, +1 hour: 1.3 +/- 0.9, +2 hours: 4.1 +/- 0.9), peaking at +3 hours (10 +/- 1.9 TF mRNA molecules per monocyte). As TF mRNA levels increased, thrombin generation was augmented. Peak levels of TAT and F1 + 2 were reached later (at t +4 hours) than those of TF mRNA. TF mRNA, TAT, and F1 + 2 levels returned to baseline after 24 hours. In conclusion, we used a NASBA/ECL-based technique to quantify TF mRNA in whole blood during human endotoxemia and observed a 125-fold increase in TF mRNA levels. Our data demonstrate a pivotal role for enhanced TF gene activity in the activation of coagulation after LPS challenge. (Blood. 2000;96:554-559)     

Elevated sympathetic nervous system activity in patients with recently diagnosed rheumatoid arthritis with active disease

OBJECTIVE: To investigate sympathetic (SNS) and parasympathetic (PNS) nervous system activity in patients with recently diagnosed rheumatoid arthritis (RA), and to analyze the association between activity of these systems and disease activity, and complaints that frequently occur in RA, viz., pain, fatigue, negative mood, and stiffness. METHODS: To assess sympathetic and parasympathetic nervous activity, the Pre-Ejection-Period (PEP) and Respiratory Sinus arrhythmia (RSA) were measured on two consecutive nights in a real-life environment in 25 patients with RA [19 female (f), 6 male (m), mean age 55.2 years) and 28 healthy controls (20f, 8m, mean age 55.8 years]. RESULTS: Patients showed a significantly shorter PEP (reflecting elevated SNS activity) compared to healthy controls, an effect that was most pronounced in those with active disease. RSA and the heart period did not differ between patients and healthy controls. The heart period was significantly associated with stiffness, but neither PEP nor RSA were associated with pain, fatigue, mood, or stiffness. CONCLUSION: Our study showed that cardiac sympathetic nervous system activity is elevated in RA, whereas cardiac parasympathetic activity remains at a normal level. Our results suggest that inflammatory stress rather than the common symptoms of RA challenge the SNS.     

the potential of AGE MODE, an age-dependent model, to estimate usual intakes and prevalences of inadequate intakes in a population

Dietary intake data often stem from short-term measurements. However, for dietary assessment, generally the habitual intake distribution is of interest. Currently, habitual intake distributions are often estimated separately for subgroups of gender and age and do not take into account the variation in intake caused by age within age groups. Therefore, we developed an age-dependent dietary assessment model, which was demonstrated and tested using folate intakes from the third Dutch National Food Consumption Survey, conducted in 1997/98. The proposed model produced estimates of the mean habitual intake and intake percentiles as a function of age. The methodology has clear advantages in estimating habitual intakes in children. Also, given the large variation in intakes of several dietary components, estimated habitual intakes produced by other methods may have low precision and be less reliable if numbers are small. In our age-dependent model, all available data can be used to estimate the parameters of the habitual intake distribution, improving the precision of the estimates, and providing consistent estimates for a larger population sample as no subgroups need to be created. Although the model may still be further developed, the feature of age dependency shows clear advantages above methods currently used to estimate habitual intakes.     

Biopsychosocial mediators and moderators of stress-health relationships in patients with recently diagnosed rheumatoid arthritis

OBJECTIVE: To investigate the mediating and moderating roles of social support, coping, and physiological variables in the relationship between life events and health status. METHODS: Psychological and biological measurements were taken in 54 patients (38 women, 16 men, mean age +/- SD 56 +/-14.4 years) with recently diagnosed rheumatoid arthritis (RA). RESULTS: Life events were correlated with psychological distress, but not with disease activity. No mediators for the relationship of life events with psychological well-being and disease activity were observed. In 40 tests, 4 moderators were found: Problem-focused coping, perceived support, diastolic blood pressure, and total number of lymphocytes were moderators of the relationship between daily hassles and health status (P < or = 0.05). CONCLUSION: Our study provides limited support for the notion that the interactions of life stress with biopsychosocial variables have an impact on health. None of these variables were found to be crucial mediators of stress-health associations in recently diagnosed patients with RA, but some provocative evidence was given that biopsychosocial variables may have a minor impact on stress-health relationships.     

Endoscopic vs. microscopic transsphenoidal surgery for Cushing’s disease: a systematic review and meta-analysis

Purpose

Systematic review and meta-analysis comparing endoscopic and microscopic transsphenoidal surgery for Cushing’s disease regarding surgical outcomes (remission, recurrence, and mortality) and complication rates. To stratify the results by tumor size.

Methods

Nine electronic databases were searched in February 2017 to identify potentially relevant articles. Cohort studies assessing surgical outcomes or complication rates after endoscopic or microscopic transsphenoidal surgery for Cushing’s disease were eligible. Pooled proportions were reported including 95% confidence intervals.

Results

We included 97 articles with 6695 patients in total (5711 microscopically and 984 endoscopically operated). Overall, remission was achieved in 5177 patients (80%), with no clear difference between both techniques. Recurrence was around 10% and short term mortality <?0.5% for both techniques. Cerebrospinal fluid leak occurred more often in endoscopic surgery (12.9 vs. 4.0%), whereas transient diabetes insipidus occurred less often (11.3 vs. 21.7%). For microadenomas, results were comparable between both techniques. For macroadenomas, the percentage of patients in remission was higher after endoscopic surgery (76.3 vs. 59.9%), and the percentage recurrence lower after endoscopic surgery (1.5 vs. 17.0%).

Conclusions

Endoscopic surgery for patients with Cushing’s disease reaches comparable results for microadenomas, and probably better results for macroadenomas than microscopic surgery. This is present despite the presumed learning curve of the newer endoscopic technique, although confounding cannot be excluded. Based on this study, endoscopic surgery may thus be considered the current standard of care. Microscopic surgery can be used based on neurosurgeon’s preference. Endocrinologists and neurosurgeons in pituitary centers performing the microscopic technique should at least consider referring Cushing’s disease patients with a macroadenoma.