The effect HBOC-201 and sodium nitrite resuscitation after uncontrolled haemorrhagic shock in swine

BackgroundDevelopment of Haemoglobin-based oxygen carriers (HBOCs) as blood substitutes has reached an impasse due to clinically adverse outcomes attributed to vasoconstriction secondary to nitric oxide (NO) scavenging. Studies suggest haemoglobin exhibits nitrite reductase activity that generates NO and N₂O₃; harnessing this property may offset NO scavenging. Therefore, the effects of concomitantly infusing sodium nitrite (NaNO₂) with HBOC-201 were investigated.MethodsSwine underwent uncontrolled liver haemorrhage before receiving up to three 10 min 10 ml/kg infusions of HBOC-201 (HBOC) with or without concurrent NaNO₂ (5.4 μmol/kg [LD NaNO₂] or 10.8 μmol/kg [HD NaNO₂]) or 6% Hetastarch (HEX) with or without HD NaNO₂ during “prehospital” resuscitation (15, 30 and 45 min after injury). Definitive surgical care occurred at 75 min; anaesthetic recovery at 120 min. Animals were euthanised at 72 h.ResultsNaNO₂ temporarily reduced systemic and pulmonary blood pressure increases from HBOC in a dose-dependent fashion. There was no significant effect between groups in indices of tissue oxygenation or survival. Adverse clinical signs requiring humane euthanasia occurred with highest frequency after HBOC + HD NaNO₂ (3 of 4 pigs) and HBOC + LD NaNO₂ (2 of 4 pigs). Gross evidence of pulmonary congestion was observed in 5 of 8 swine receiving a HBOC and NaNO₂ combination compared to 1 of 16 swine receiving HBOC alone, HEX alone, or HEX + NaNO₂. Gross lesions correlated with histological evidence of pulmonary oedema and congestion, and in 2 of 4 HBOC + HD NaNO₂ pigs, pulmonary fibrin thrombi also were found. No other pig had similar evidence of thrombi. Asymmetric pre-resuscitation cardiac index was a potential confounder.ConclusionsA significant interaction between NaNO₂ and HBOC-201 ameliorated HBOC-201 vasoconstrictive effects, consistent with HBOC possessing a nitrite reductase activity that generates vasodilator NO equivalents. Results were relatively equivalent in survival and markers of tissue oxygenation. The highest dose of NaNO₂ was the most effective in reducing HBOC-associated pulmonary and systemic vasoactivity but also with the highest incidence of adverse events. In this model, the transient nature of NaNO₂ in off-setting HBOC-201 vasoconstriction makes it less clinically promising than anticipated and the combination of NaNO₂ and HBOC appear to increase the risk of pulmonary complications in a dose-dependent fashion independently of haemodilutional effects on haemostatic components.     

Biological fixation of hydroxyapatite-coated versus grit-blasted titanium hip stems: a canine study

BACKGROUND: The purpose of the study was to evaluate the influence of a proximal hydroxyapatite (HA) coating in comparison with a grit-blasted titanium surface of an anatomic hip stem in an animal model over a maximum duration of 2 years. METHODS: Thirty adult dogs underwent implantation of either a proximally HA-coated or a grit-blasted anatomic titanium stem. The animals were clinically evaluated for their walking ability, and serial radiographs were taken. The femora were assessed histomorphologically at set time points from 6 weeks to 2 years postoperatively. Undecalcified thin section specimens through the proximal and distal portion of the coating or grit blasting were prepared. The percentage of implant surface with direct bone contact without connective tissue involvement was determined. RESULTS: Radiographically, animals with uncoated prostheses showed characteristic signs of loosening more frequently. Histomorphometrically, an average of 65% of the surface of HA-coated implants had bone contact, but only 14.7% of the surface of grit-blasted prostheses ( p=0.0001). There was no relationship between bone contact and the duration of implantation of the prosthesis, either for the coated or for the uncoated prostheses. HA coating enhances osseointegration of an anatomic hip stem. CONCLUSION: Anatomic stems with rounded design require a surface coating or surface structure, since the mere grit-blasting of the titanium surface does not ensure osseointegration in this animal model.     

Comparative Anatomy of the Subsynovial Connective Tissue in the Carpal Tunnel of the Rat, Rabbit, Dog, Baboon, and Human

The tenosynovium in the human carpal tunnel is connected to the flexor tendons and the median nerve by the subsynovial connective tissue (SSCT). The most common histological finding in carpal tunnel syndrome (CTS), a compression neuropathy of the median nerve, is noninflammatory fibrosis of the SSCT. The relationship, if any, between the fibrosis and nerve pathology is unknown, although some have speculated that a change in the SSCT volume or stiffness might be the source of the compression. Yet, while animal models have been used to study the physiology of nerve compression, so far none have been used to study the relationship of the SSCT pathology to the neurophysiological abnormalities. The purpose of this study was to identify animal models that might be appropriate to study the interaction of SSCT and nerve function in the development of CTS. The front paws of a rat, rabbit, dog, and baboon were dissected. The carpal tunnel anatomy and SSCT of these animals were also examined by light and scanning microscopy and compared to the relevant human anatomy and ultrastructure. The carpal tunnel anatomy and contents of the baboon and rabbit are similar to humans. The canine carpal tunnel lacks the superficial flexor tendons and the rat carpal tunnel is very small. The human, baboon, and rabbit specimens had very similar organization of the SSCT, and content of the carpal canal. We conclude that, while both the baboon and rabbit would be good animal models to study the relationship of the SSCT to CTS, the rabbit is likely to be more practical, in terms of cost and animal care concerns.     

Evidence for a curvilinear relationship between posttraumatic growth and posttrauma depression and PTSD in assault survivors

Two studies of assault survivors (Ns = 180, 70) examined associations between posttraumatic growth (PTG) and posttrauma psychopathology. Both studies found significant curvilinear associations between PTG and posttraumatic stress disorder, whereas only Study 1 found a curvilinear association between PTG and depression symptom severity. Survivors with no or high growth levels reported fewer symptoms than those who reported moderate growth. Study 1 also investigated potential PTG predictors. Non‐Caucasian ethnicity, religiousness, peritraumatic fear, shame, and ruminative thinking style, assessed at 2 weeks, predicted growth at 6 months. Posttraumatic growth may thus be most relevant in trauma survivors who attach enduring significance to the trauma for their lives and show initial distress. Moderate levels of PTG do not seem to ameliorate posttrauma psychopathology.     

Wavelet analysis of cutaneous blood flow in melanocytic skin lesions

Laser Doppler flowmetry (LDF) is frequently used to study the microcirculation. Usually LDF time series are analyzed by conventional linear methods, mainly Fourier analysis. The aim of this study was to observe dynamic blood perfusion of the skin in malignant and benign melanocytic skin lesions. Wavelet transformation was performed on each LDF time series in order to calculate a vasomotion field. First, the differences in vasomotion between healthy and pigmented skin were evaluated visually on six different time scales of the vasomotion field. In order to quantify the findings, vasomotion scale variance (VSV) was calculated for each scale plane of the vasomotion field. These VSV were compared using contrast DeltaVSV to determine the difference between healthy skin and a pigmented skin lesion in the same patient. After the measurements, the skin lesions were excised and examined histologically. We found that wavelet analysis of LDF time series is a specific, sensitive method for the in vivo identification of malignant melanoma. It is a non-invasive procedure and takes minimal time to be carried out.     

Dendritic cells process synthetic long peptides better than whole protein,improving antigen presentation and T‐cell activation

The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte‐derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4⁺ and CD8⁺ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome‐ and transporter associated with Ag processing‐dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD8⁺ T‐cell activation.     

Evozierte Potenziale bei visuellen Auren – auch heute noch der Schlüssel zur Diagnose

Clinical Epileptology - Wir berichten über einen jungen Patienten mit einer seltenen Form einer progressiven Myoklonusepilepsie. Der langwierige Weg zur richtigen Diagnose, der unterem anderem...