Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

Monitoring of direct alcohol markers in alcohol use disorder patients during withdrawal treatment and successive rehabilitation

Direct and indirect biomarkers are widely applied for the determination of alcohol consumption. They help to assess past or present alcohol consumption. Depending on the window of detection and sensitivity of the investigated marker, punctual alcohol consumption may remain undetected. In this study, different sampling strategies for the intermediary long‐term marker phosphatidylethanol (PEth) are evaluated and compared to the determination of the short‐term markers ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine. Samples from 19 patients undergoing alcohol use disorder treatment were collected during the withdrawal treatment and successive rehabilitation (33 ± 26 days (range: 3–74 days)). With liquid chromatography–tandem mass spectrometry (LC–MS/MS) EtG and EtS in urine, PEth in blood, PEth in dried blood spot (DBS) from venous blood, and PEth in DBS from capillary blood were quantified and compared. The use of volumetric capillary DBS, prepared from 20 μL of blood, provided the same results as the use of venous DBS (95% ± 10%, R² 0.9899 for PEth 16:0/18:1). Capillary DBS sampling has the advantage that it can be performed without venipuncture. The use of PEth in DBS proved to prevent post‐sampling degradation, providing a longer detection in comparison to PEth in liquid blood, which only showed 67% ± 24% of the PEth DBS 16:0/18:1 concentration. When compared with EtG and EtS in urine, PEth monitoring proved to be advantageous for the detection of relapse situations, as the accumulation of PEth in blood prolongs the detectability. In conclusion, volumetric capillary DBS sampling for PEth is a simple and useful tool for compliance monitoring, and avoids hematocrit issues.     

Versagen der Atempumpe

The total anatomical and functional apparatus which allows normal ventilation of the lungs is known as the respiratory pump. An insufficiency of this system, which can be caused by a multitude of reasons, primarily affects the inspiratory musculature and especially the diaphragm. One of the essential clinical characteristics is rapid shallow breathing. Exhaustion of the repiratory musculature due to acute respiratory insufficiency is normally clinically registered but can also be functionally determined in particular by the maximum static inspiratory closed mouth pressure. A further option is invasive measurement of the transdiaphragmal pressure, which however is not suitable as a routine procedure. Mechanical ventilation is used as treatment of respiratory pump insufficiency independent of the cause. This is initially a non-invasive procedure but if unsuccessful intubation and invasive ventilation are indicated. The technical developments in the field of extracorporeal gas exchange systems are very promising. However, in view of the insufficient data, ventilation procedures using masks and tubes still remain the first choice methods.     

The phenotype of human STK4 deficiency

We describe a novel clinical phenotype associating T- and B-cell lymphopenia, intermittent neutropenia, and atrial septal defects in 3 members of a consanguineous kindred. Their clinical histories included recurrent bacterial infections, viral infections, mucocutaneous candidiasis, cutaneous warts, and skin abscesses. Homozygosity mapping and candidate gene sequencing revealed a homozygous premature termination mutation in the gene STK4 (serine threonine kinase 4, formerly having the symbol MST1). STK4 is the human ortholog of Drosophila Hippo, the central constituent of a highly conserved pathway controlling cell growth and apoptosis. STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome.     

The management of trauma victims with head injury: a study by the national confidential enquiry into patient outcome and death

Introduction

In 2006 the National Confidential Enquiry into Patient Outcome and Death undertook a large prospective study of trauma care, which revealed several findings pertaining to the management of head injuries in a sample of 493 patients.

Methods

Case note data were collected for all trauma patients admitted to all hospitals accepting emergencies in England, Wales, Northern Ireland and the Channel Islands over a three-month period. Severely injured patients with an injury severity score (ISS) of ≥16 were included in the study. The case notes for these patients were peer reviewed by a multidisciplinary group of clinicians, who rated the overall level of care the patient received.

Results

Of the 795 patients who met the inclusion criteria for the study, 493 were admitted with a head injury. Room for improvement in the level of care was found in a substantial number of patients (265/493). Good practice was found to be highest in high volume centres. The overall head injury management was found to be satisfactory in 84% of cases (319/381).

Conclusions

This study has shown that care for trauma patients with head injury is frequently rated as less than good and suggests potential long-term remedies for the problem, including a reconfiguration of trauma services and better provision of neurocritical care facilities.     

Risk stratification by injury distribution in polytrauma patients – does the clavicular fracture play a role?

Background

Thoracic and extremity injuries are common in polytraumatized patients. The clavicle limits the upper thoracic cage and connects the body and upper extremities. It is easy to examine and is visible on standard emergency room radiographs. We hypothesize that clavicular fracture in polytrauma patients indicates the presence of further injuries of the upper extremities, head, neck and thorax.

Material and methods

Retrospective study including patients admitted between 2008 and 2012 to a level-I trauma center. Inclusion criteria: ISS?>?16, two or more injured body regions, clavicular fracture. Control group: patients admitted in 2011, ISS?>?16, two or more injured body regions, no clavicular fracture. Patient information was obtained from the patients’ charts; evaluation of radiographic findings was performed; scoring was based on the Abbreviated Injury Scale (AIS) and Injury Severity Score (ISS) AIS/ISS; data were analyzed using Pearson’s correlation and the Mann–Whitney U-test in SPSS (version 11.5.1); graphs were drawn using EXCEL®.

Results

Thirty-four patients with clavicular fracture (C+) and 40 without (C-) were included; the mean ISS was 25 (range 16–57), m?=?70%, f?=?30%; age 43.3 years (range 9–88); clavicular fractures were positively correlated with severe thoracic (p?=?0.011, OR 4.5: KI 1.3–15.3), external (p?<?0.001, OR 9.2: KI 2.7–30.9) and upper extremity injuries (p?<?0.001, OR 33.2: KI 6.9–16.04 resp. p?=?0.004, OR 12.5: KI 1.5–102.9). C?+?showed a lower head/neck AIS (p?=?0.033), higher thorax AIS (p?=?0.04), arm/shoulder AIS (p?=?0.001) and external AIS (0.003) than C-. Mean hospital stay and ICU treatment time were longer in the C?+?group (p?=?0.001 and p?=?0.025 respectively).

Conclusion

A clavicular fracture can be diagnosed easily and may be used as a pointer for further thoracic and upper extremity injuries in polytrauma patients that might have been otherwise missed. Special attention should be paid on second and tertiary survey.

     

Improved dental adhesive formulations based on reactive nanogel additives

Current challenges in adhesive dentistry include over-hydrophilic bonding formulations, which facilitate water percolation through the hybrid layer and result in unreliable bonded interfaces. This study introduces nanogel-modified adhesives as a way to control the material's hydrophobic character without changing the basic monomer formulation (keeping water-chasing capacity and operatory techniques unaltered). Nanogel additives of varied hydrophobicity were synthesized in solution, rendering 10- to 100-nm-sized particles. A model BisGMA/HEMA solvated adhesive was prepared (control), to which reactive nanogels were added. The increase in adhesive viscosity did not impair solvent removal by air-thinning. The degree of conversion in the adhesive was similar between control and nanogel-modified materials, while the bulk dry and, particularly, the wet mechanical properties were significantly improved through nanogel-based network reinforcement and reduced water solubility. As preliminary validation of this approach, short-term micro-tensile bond strengths to acid-etched and primed dentin were significantly enhanced by nanogel inclusion in the adhesive resins.