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.     

Cross Validation of the b Test in a Large Known Groups Sample

The b Test (Boone, Lu, & Herzberg, 2002a) is a measure of cognitive performance validity originally validated on 91 non-credible participants and 7 credible clinical comparison groups (total n?=?161). The purpose of the current study was to provide cross-validation data for the b Test on a known groups sample of non-credible participants (n?=?212) and credible heterogeneous neuropsychological clinic patients (n?=?103). The new data showed that while the original E-score cut-off of ≥155 achieved excellent specificity (99%), it was associated with relatively poor sensitivity (41%). However, the cut-off could be substantially lowered to ≥82, while still maintaining adequate specificity (≥90%) and raising sensitivity to 68%. Examination of non-credible subgroups revealed that b Test sensitivity in feigned mild traumatic brain injury (mTBI) was 58%, whereas in non-credible patients claiming depression and psychosis, cut-off sensitivity was 76% and 67%, respectively. These data suggest that the b Test may have a particular role in detection of non-credible cognitive symptoms associated with feigned psychiatric symptoms, and that fabricated deficits in processing speed and vigilance/visual scanning, detected by the b Test, are more prominent in feigned psychiatric presentations than in feigned mTBI. Further, b Test failures in patients with somatoform disorders were common, indicating that the b Test may have a specific use in detection of non-consciously created cognitive dysfunction associated with somatoform conditions.     

Re-Examination of the Rey Word Recognition Test

The Rey Word Recognition Test, a brief and simple to administer free-standing neurocognitive performance validity test, was examined in a large known-groups sample (122 credible patients and 134 non-credible patients). Total correctly recognized was the most sensitive score, identifying 54% of non-credible participants using a cut-off of ≤6, while maintaining specificity of approximately 90%. However, specifically rates were somewhat lower in credible individuals with <12 years of education or borderline intelligence, or who were bilingual (spoke English as a second language, or learned English concurrently with another language), indicating that cut-offs may require minor adjustment in these groups. Sensitivity rates were much higher in non-credible female versus male mild traumatic brain injury patients (mTBI; 68% versus 48% for total correct), suggesting that the Rey Word Recognition Test is particularly effective in identifying performance invalidity in female mTBI compensation seekers.     

Reduction in length of stay for patients undergoing oesophageal and gastric resections with implementation of enhanced recovery packages

Introduction

The high mortality and morbidity associated with resection for oesophagogastric malignancy has resulted in a conservative approach to the postoperative management of this patient group. In August 2009 we introduced an enhanced recovery after surgery (ERAS) pathway tailored to patients undergoing resection for oesophagogastric malignancy. We aimed to assess the impact of this change in practice on standard clinical outcomes.

Methods

Two cohorts were studied of patients undergoing resection for oesophagogastric malignancy before (August 2008 – July 2009) and after (August 2009 – July 2010) the implementation of the ERAS pathway. Data were collected on demographics, interventions, length of stay, morbidity and in-hospital mortality.

Results

There were 53 and 55 oesophagogastric resections undertaken respectively for malignant disease in each of the study periods. The median length of stay for both gastric and oesophageal resection decreased from 15 to 11 days (Mann– Whitney U, p<0.001) following implementation of the ERAS pathway. There was no significant increase in morbidity (gastric resection 23.1% vs 5.3% and oesophageal resection 25.9% vs 16.7%) or mortality (gastric resection no deaths and oesophageal resection 1.8% vs 3.6%) associated with the changes. There was a significant decrease in the number of oral contrast studies used following oesophageal resection, with a reduction from 21 (77.8%) in 2008–2009 to 6 (16.7%) in 2009–2010 (chi-squared test, p<0.0001).

Conclusions

The introduction of an enhanced recovery programme following oesophagogastric surgery resulted in a significant decrease in length of median patient stay in hospital without a significant increase in associated morbidity and mortality.     

Stroke management: updated recommendations for treatment along the care continuum

The Australian Clinical Guidelines for Stroke Management 2010 represents an update of the Clinical Guidelines for Stroke Rehabilitation and Recovery (2005) and the Clinical Guidelines for Acute Stroke Management (2007). For the first time, they cover the whole spectrum of stroke, from public awareness and prehospital response to stroke unit and stroke management strategies, acute treatment, secondary prevention, rehabilitation and community care. The guidelines also include recommendations on transient ischaemic attack. The most significant changes to previous guideline recommendations include the extension of the stroke thrombolysis window from 3 to 4.5 h and the change from positive to negative recommendations for the use of thigh-length antithrombotic stockings for deep venous thrombosis prevention and the routine use of prolonged positioning for contracture management.