Protection with Antibody to Tumor Necrosis Factor Differs with Similarly Lethal Escherichia coli versus Staphylococcus aureus Pneumonia in Rats

Background: Differing factors may alter the effects of antibody to tumor necrosis factor (TNF) in infection and sepsis. The authors tested whether bacteria type or treatment route alters antibody to TNF in a rat model of bacterial pneumonia.

Methods: Rats (n = 231) received similarly lethal doses of either intratracheal Escherichia coli or Staphylococcus aureus followed by treatment with either intratracheal or intraperitoneal antibody to TNF or control serum. Animals received antibiotics (cefotiam daily dose, 100 mg/kg) starting 4 h after inoculation and were studied for up to 96 h.

Results: Compared with S. aureus, E. coli increased serum TNF and interleukin-6 concentrations, lung lavage TNF concentrations, neutrophil counts, and alveolar-to-arterial oxygen gradients and decreased circulating neutrophils and lymphocytes (P >= 0.05 for all). Compared with controls, with both bacteria, except for lung lavage TNF concentrations (which decreased with intratracheal but not with intraperitoneal antibody to TNF), treatment route did not alter the effects of antibody to TNF on any parameter (P = not significant for all). Antibody to TNF reduced mortality rates (relative risk of death +/- SEM) with both E. coli (-1.6 +/- 0.6;P = 0.006) and S. aureus (-0.5 +/- 0.04;P = 0.185), but these reductions were greater with E. coli than with S. aureus in a trend approaching statistical significance (P = 0.09). Compared with controls, similarly (P = not significant) with both bacteria, antibody to TNF decreased lung lavage and tissue bacteria concentrations (both P < 0.05) and serum TNF concentration (P < 0.09) and increased circulating neutrophils and lymphocytes (both P <= 0.01). Compared with S. aureus, with E. coli antibody to TNF decreased alveolar-to-arterial oxygen gradients (P = 0.04) and increased serum interleukin-6 concentrations (P = 0.003).     

Tissue engineered venous matrices for potential applications in the urogenital tract

Tissue engineering is lacking inexpensive, easily applicable techniques for tissue replacement. We investigated the potential use of native veins for tissue-engineering applications in the urological field. Forty-eight porcine veins, half seeded with urothelial cells and half unseeded, were kept in vitro for 7 days. Four seeded and four unseeded scaffolds were analyzed after 3 and 7 days. The remaining 32 veins were implanted subcutaneously into 16 athymic mice. Four athymic mice were sacrificed after 2, 4, 8, and 12 weeks. Histochemistry, immunohistochemistry (anti-pancytokeratin AE1/AE3, anti-desmin), western blot analyses (CD31), and scanning electron microscopy were performed in the retrieved specimens. The histochemistry of the seeded matrices showed the presence of urothelial cells in vitro and in vivo. After 12 weeks, a multilayer of urothelial cells was present in the hemotoxylin and eosin staining, positive for anti-pancytokeratin AE1/AE3. The western blot analyses showed vascularization of the veins in vivo. The results of scanning electron microscopy revealed a cellular layer on the veins. Native venous matrices may be used as tissue-engineered constructs for reconstructing the urinary tract. The clinical relevance of this approach must be proven in a large-animal model.     

N-terminal pro brain natriuretic peptide in arterial hypertension--a marker for left ventricular dimensions and prognosis

In arterial hypertension risk factor evaluation, including LV mass measurements, and risk stratification using risk charts or programs, is generally recommended. In heart failure NT-proBNP has been shown to be a marker of LV dimensions and of prognosis. If the same diagnostic and prognostic value is present in arterial hypertension, risk factor evaluation would be easier. In 36 patients with arterial hypertension, electrocardiographic LV hypertrophy and preserved left ventricular function, NT-proBNP was eight-fold higher than in healthy subjects. The log NT-proBNP correlated with LV mass index (R=0.47, P=0.0002) measured by magnetic resonance imaging. In other subjects with arterial hypertension a significant but weak correlation to diastolic properties has been demonstrated. As for prognosis, a recent study in patients with hypertension, electrocardiographic left ventricular hypertrophy and preserved LV function demonstrated that NT-proBNP was a very strong prognostic marker, especially combined with a history of cardiovascular disease. Patients with high NT-proBNP and known cardiovascular disease had a seven-fold increase in CV events compared to patients with low NT-proBNP and no CV disease, while patients with either high NT-proBNP or CV disease had a three-four-fold increased risk. In conclusion NT-proBNP predicts LV mass in hypertensive patients and is a very strong prognostic marker in these patients. This could indicate a use of NT-proBNP in the future for risk stratification and perhaps monitoring of treatment in patients with arterial hypertension.     

Experimental validation of the RATE tool for inferring HLA restrictions of T cell epitopes

Background

The RATE tool was recently developed to computationally infer the HLA restriction of given epitopes from immune response data of HLA typed subjects without additional cumbersome experimentation.

Results

Here, RATE was validated using experimentally defined restriction data from a set of 191 tuberculosis-derived epitopes and 63 healthy individuals with MTB infection from the Western Cape Region of South Africa. Using this experimental dataset, the parameters utilized by the RATE tool to infer restriction were optimized, which included relative frequency (RF) of the subjects responding to a given epitope and expressing a given allele as compared to the general test population and the associated p-value in a Fisher’s exact test. We also examined the potential for further optimization based on the predicted binding affinity of epitopes to potential restricting HLA alleles, and the absolute number of individuals expressing a given allele and responding to the specific epitope. Different statistical measures, including Matthew’s correlation coefficient, accuracy, sensitivity and specificity were used to evaluate performance of RATE as a function of these criteria. Based on our results we recommend selection of HLA restrictions with cutoffs of p-value?<?0.01 and RF?≥?1.3. The usefulness of the tool was demonstrated by inferring new HLA restrictions for epitope sets where restrictions could not be experimentally determined due to lack of necessary cell lines and for an additional data set related to recognition of pollen derived epitopes from allergic patients.

Conclusions

Experimental data sets were used to validate RATE tool and the parameters used by the RATE tool to infer restriction were optimized. New HLA restrictions were identified using the optimized RATE tool.

     

Cervical range of motion and strength in 4,293 young male adults with chronic neck pain

Purpose

The correlation of cervical biomechanics and neck pain in young patients has, to date, only been described in terms of small cohorts. This study focuses on the correlation of chronic neck pain and cervical biomechanics.

Methods

Neck pain, cervical range of motion (CROM) and maximal cervical torque were recorded in 746 patients with conservatively treated chronic neck pain and 3,547 participants of physiotherapy training without chronic neck pain aged 16–32 years.

Results

The “neck pain” group had a highly significant (s < 0.001) higher neck disability index (44.7 vs. 10.4 %), longer history of neck pain (3.47 vs. 0.59 years), higher pain intensity (VAS 5.93 vs. 0.93), higher pain frequency (VAS 6.98 vs. 1.09). No differences of CROM and maximal torque in the sagittal, frontal and transverse plane were found.

Conclusion

This study describes the largest cohort of biomechanical data of the cervical spine in young adult recorded to date. The findings demonstrate that no correlation was found between neck pain, CROM and maximal torque in the study cohort. On this basis, we conclude that the CROM and maximal cervical torque should not be used as indicators to measure the progress of chronic neck pain in physiotherapy training and sports medicine for the young adult.