Monocyte deactivation in severe human sepsis or following cardiopulmonary bypass

We investigated the specificity for gram-negative stimuli as well as the contribution of signal transduction pathways for leukocyte hyporesponsiveness in sepsis or following cardiopulmonary bypass (CPB). Whole blood of nine patients undergoing CPB and 25 patients with severe sepsis was stimulated ex vivo with LPS (E. coli O111:B4) or with Staphylococcus aureus Cowan strain I (SAC-I) lysate in the absence or presence of inhibitors of protein kinase C (PKC), protein-tyrosine kinase (PTK), or protein-tyrosine phosphatase (PTP). Both toxins stimulated a TNF-alpha response through PTK signaling. Although suppression of the cytokine response was similar for LPS and SAC-I after CPB, it was significantly more pronounced for SAC-I in sepsis. Inhibition of PTP failed to increase TNF-alpha upon LPS, whereas a moderate increase was observed with SAC-I. Impaired TNF-alpha responses occur in sepsis and after CPB. Although this has primarily been reported for gram-negative stimuli, our data suggest that this is even more pronounced for gram-positive stimuli in severe sepsis. Although PTK was the predominant signaling pathway, inhibition of PTP only partially restored the TNF-alpha response to SAC-I. Our results suggest that cellular mechanisms underlying monocyte deactivation are different in sepsis or following CPB and are discriminate for gram-positive and gram-negative toxins.     

Serum leptin concentration, adiposity, and body fat distribution in Mexican-Americans

BACKGROUND: Leptin is strongly associated with adiposity and few studies have investigated its role in Mexican-Americans. The aims of this study were to examine the association of serum leptin concentration with adiposity and body fat distribution in Mexican-Americans and to develop a predictive model of serum leptin concentration for this ethnic group. METHODS: Three hundred fifty-two college students (242 women, 110 men; age 18-30 years) were evaluated in this cross-sectional study. Body fat content was assessed using bioelectrical impedance analysis. Correlation between serum leptin levels and several markers of adiposity and body fat distribution were examined in both men and women. Multiple regression analysis was performed to create the predictive model. RESULTS: Women had higher serum leptin concentrations than men for the same levels of adiposity. After controlling for gender and body fat, only fat mass (FM) expressed in kg, was significantly correlated with serum leptin concentration in men (partial rho = 0.811, p <0.001), whereas body mass index (BMI), hip circumference (HC), and FM expressed in kg, were significantly correlated with serum leptin concentration in women (partial rho = 0.214, p <0.001; partial rho = 0.201, p <0.01; and partial rho = 0.818, p <0.001, respectively). Percent body fat (PBF) was the only significant predictor of serum leptin concentration among men, explaining 42% of the variance in serum leptin concentration. In addition to PBF, waist circumference (WC) and HC were significant predictors of serum leptin concentration among women explaining 65% of the variance in serum leptin concentration. CONCLUSIONS: Serum leptin concentration is a function of adiposity as determined by PBF in both Mexican-American men and women. HC and WC are associated with serum leptin concentration in Mexican-American women but not in men. BMI alone should not be used in evaluating the association of serum leptin concentration with body fatness in Mexican-Americans.     

Children in out‐of‐home care: Does routine health screening improve outcomes?

Aim:   Children in out-of-home care have high and frequently unidentified health needs. The Child Protection Unit at Sydney Children's Hospital offers comprehensive health screening to children in care. Recommendations for remediation are made, but follow-up in the clinic is not offered. Current research has failed to establish whether health screening results in health benefits for the children screened. The aim of this study was to assess the impact of the health screening clinic on children's health outcomes by tracking the first 100 children screened, determining how many of the health recommendations made for each child had been implemented and, if possible, what the health outcome had been.
Methods:   Research questionnaires were sent to the Department of Social Services caseworkers of the first 100 children screened.
Results:   Adherence to health recommendations was high; however, it was not possible to quantify the degree of health benefit to the children screened. A number of systemic problems were identified, which are likely to hinder the accessibility of health care for children in care.
Conclusions:   Comprehensive health screening of children in care is likely to benefit a child's health, although this could not be determined. Agencies responsible for placing children in care need systems in place to ensure better inter-agency collaboration between the health system and community services. This should help improve health outcomes.     

Indices of fetal development derived from heart rate patterns

Background

The fetal precursors of mental and cardiovascular disease caused by adverse prenatal environmental influences and manifesting in later age are an important issue of developmental medicine. However the number of measurable functional parameters of a fetus is limited. Evaluation of key parameters involving fetal autonomic control could permit an earlier detection of developmental problems and improved therapeutic strategies. Thus far, however, even the maturation of normal autonomic control has not been sufficiently assessed.

Aim

The objective of the present work is to describe normal fetal maturation based on indices of autonomic heart rate modulation.

Study design

Heart beat interval series were magnetocardiographically recorded with 1 kHz sampling rate over 30 min in 78 normal fetuses, gestational age (GA) 23-40 weeks. Indices considered were: number of accelerations (AC) and decelerations (DC), RMSSD, SDNN, and short-term/long-term autonomic information flows (AIF_NN, AIF_fVLF). These were measured from the entire 30 min data sets and from activity-specific subsets (10 min).

Results

In the 30 min recordings: the number of AC increased, number of DC decreased, rMSSD and SDNN increased and AIF_fVLF increased with GA, but AIF_NN remained constant. In the 10 min subsets: SDNN increased in the active state but remained constant in the quiet state and AIF_NN decreased with GA in the quiet state.

Conclusion

Heart rate patterns from 30 min biomagnetic recordings may provide new indices with which to assess the normal and abnormal maturation of fetal autonomic control and to identify risk of possible disorders in later life.     

Proton pump inhibitors: Risks of long‐term use

Proton pump inhibitors are among the most commonly prescribed classes of drugs, and their use is increasing, in particular for long‐term treatment, often being over‐prescribed and used for inappropriate conditions. In recent years, considerable attention has been directed towards a wide range of adverse effects, and even when a potential underlying biological mechanism is plausible, the clinical evidence of the adverse effect is often weak. Several long‐term side effects have been investigated ranging from interaction with other drugs, increased risk of infection, reduced intestinal absorption of vitamins and minerals, and more recently kidney damage and dementia. The most recent literature regarding these adverse effects and their association with long‐term proton pump inhibitor treatment is reviewed, and the mechanisms through which these possible complications might develop are discussed.     

Bone healing in the rat and dog with nonglycosylated BMP-2 demonstrating low solubility in fibrin matrices.

A novel form of recombinant human bone morphogenetic protein-2 (BMP-2) was explored for effective incorporation and long-term retention into fibrin ingrowth matrices. The solubility of native BMP-2 is greatly dependent on its glycosylation. To enhance retention of BMP-2 in fibrin matrices, a nonglycosylated form (nglBMP-2), which is less soluble than the native glycosylated protein, was produced recombinantly and evaluated in critical-size defects in the rat calvarium (group n=6). When 1 or 20 microg nglBMP-2 was incorporated by precipitation within the matrix, 74 +/- 4% and 98 +/- 2% healing was observed in the rat calvarium, respectively, as judged radiographically by closure of the defect at 3 weeks. More soluble forms of BMP-2, used as controls, induced less healing, demonstrating a positive correlation between low solubility, retention in vitro, and healing in vivo. Subsequently, the utility of nglBMP-2 was explored in a prospective veterinary clinical trial for inter-carpal fusion in dogs, replacing the standard-of-care, namely autologous cancellous autograft, with nglBMP-2 in fibrin. In a study of 10 sequential canine patients, fibrin with 600 microg/ml nglBMP-2 performed better than autograft in the first weeks of bone healing and comparably thereafter. Furthermore, a greater fraction of animals treated with nglBMP-2 in fibrin demonstrated bone bridging across each of the treated joints at both 12 and 17 weeks than in animals treated with autograft. These results suggest that evaluation in a human clinical setting of nonglycosylated BMP-2 in fibrin matrices might be fruitful.     

Clinicopathological Characteristics and Long-term Outcome in Patients with Distant Metastases from Differentiated Thyroid Cancer

Background Distant metastases are seen in a minority of patients with differentiated thyroid carcinoma (DTC) but account for most of its disease-specific mortality. Studies on the long-term outcome of patients with distant metastases are controversial. Materials and Methods We retrospectively reviewed the medical records of 660 patients with differentiated thyroid carcinoma followed at our institution from 1994 to 2004. Forty-four patients (6.7%) had distant metastases, with a prevalence of 4.8% for papillary thyroid cancer, 21% for follicular thyroid cancer, and 10% for Hurthle cell cancer. Primary near-total thyroidectomy followed by I¹³¹ radiation was performed in 97% of patients with metastases (86% operated on in 1980–2003). Mean age at thyroidectomy was 49 ± 19 years, and the female-to-male ratio was 1.9:1. Results The distant metastasis occurred synchronously with the primary tumor in 45.5% and after a median follow-up of 9 years in the others. Affected sites were lungs (n = 24), bones (n = 11), lungs and bones (n = 9), brain (n = 3), and uterus (n = 1). Median duration of follow-up was 12 years (range: 1–42 years) from thyroidectomy and 5.5 years (range: 1–24 years) from diagnosis of distant metastases. The 5- and 10-year survival rates (all causes) after diagnosis of distant metastases were 88% and 77%, respectively. No significant differences in survival curves were found by age, sex, metastasis site, histopathology, or interval to distant metastasis. Conclusions We conclude that complete resection of the thyroid gland at diagnosis and high-dose adjuvant radioactive iodine are associated with improved survival in patients with metastatic DTC.