Normal and stenotic renal arteries: experimental balloon-expandable intraluminal stenting

Elastic recoil of the vessel wall is a common cause of failure of percutaneous transluminal angioplasty in renal arteries. To oppose such recoil, balloon-expandable metal stents were implanted in artificially stenotic renal arteries in pigs and normal renal arteries in dogs and pigs. The stents were then examined angiographically and histologically at regular intervals. All stents were completely covered with endothelialized neointima in 3 weeks. There was no difference in intimal thickness between the stenotic and nonstenotic renal arteries. A large stent diameter and a large open or nonmetal surface may cause less intimal hyperplasia, but nonturbulent, fast arterial flow is probably the most important factor in ensuring long-term patency of the vessel.     

Calcium antagonists are associated with reduced mortality after cardiac surgery: a propensity analysis

OBJECTIVES: Observational studies have questioned the effectiveness of perioperative calcium channel blockers but failed to correct for selection biases. We therefore performed a prospective observational cohort study of the effects of calcium channel blockers on cardiac surgical mortality. A propensity score technique was used for risk adjustment. METHODS: We identified 6619 patients who underwent nontransplant cardiac surgery at the Toronto General Hospital (Toronto, Ontario, Canada) between May 1999 and December 2001. Propensity scores for calcium channel blocker use were constructed for the entire sample and for the subgroup (n = 5222) that underwent coronary artery bypass grafting. The calcium channel blocker adjusted odds ratio for in-hospital mortality after cardiac surgery was determined by using multiple logistic regression and propensity matched-pairs analyses. A subgroup analysis was performed for patients who underwent coronary artery bypass grafting: the calcium channel blocker adjusted odds ratio for mortality was determined by using propensity score matched-pairs analyses. RESULTS: Calcium channel blockers were associated with significantly reduced cardiac surgical mortality after adjustment with both multiple logistic regression (odds ratio, 0.56; 95% confidence interval, 0.33-0.94; P =.028) and propensity score matched-pairs analyses (odds ratio, 0.56; 95% confidence interval, 0.32-0.98; P =.042). Calcium channel blockers were also associated with reduced mortality (odds ratio, 0.48; 95% confidence interval, 0.23-0.98; P =.044) among patients who underwent coronary artery bypass grafting. CONCLUSIONS: After adjustment for baseline differences, calcium channel blockers were associated with significantly reduced mortality after cardiac surgery. This benefit also extends to the subgroup that underwent coronary artery bypass grafting. A large randomized controlled trial of perioperative calcium channel blockers is therefore warranted.     

Evaluation of validity of the STOP-BANG questionnaire in major elective noncardiac surgery

Background

The STOP-BANG questionnaire screens for obstructive sleep apnoea (OSA) in surgical patients. In prior research, the association of STOP-BANG scores with comorbidities and outcomes was inconsistent. The objective of this study was to evaluate the validity of the STOP-BANG score.

Behavioural and neurochemical responses evoked by repeated exposure to an elevated open platform

Increased psychophysiological resistance to chronic stress has been related to increased 5-HT release in the dorsal hippocampus. This study investigated the changes in 5-HT release and turnover in the hippocampus evoked by acute and repeated exposure to an inescapable stressor, an elevated open platform, and compared them to the changes evoked in the frontal cortex. Repeated exposure to this stressor results in habituation of the plasma corticosterone response to the test, with full habituation being observed after 20 trials. Repeated exposure to the stressor for 5 or 10 occasions increased 5-HT turnover in the hippocampus. By contrast, 5-HT turnover in frontal cortex was increased by acute exposure to the stressor. Microdialysis studies showed that acute stress increased 5-HT overflow in prefrontal cortex but not dorsal hippocampus whereas repeated daily (10 days) exposure to the stressor increased basal extracellular 5-HT in the dorsal hippocampus, but not the prefrontal cortex. Prior exposure to the stressor on up to 10 occasions enhanced the plasma corticosterone response to a challenge in an elevated plus-maze performed 24h later whereas repeated, but not acute, exposure to the stressor, elicited anxiolytic-like behavioural responses in this test. It is concluded that acute exposure to this form of inescapable stress selectively stimulates the 5-HT projections to the frontal cortex; repeated stress elicits a sustained increase in 5-HT release and turnover in the hippocampus. The data are consistent with the hypothesis that increased 5-HT release in the hippocampus may be implicated in the mechanisms underlying habituation to inescapable stress.     

Cognitive functioning,cognitive reserve,and residential care placement in patients with Alzheimer's and related dementias

Objective: To test the hypothesis that patients with mild to moderate dementia with higher initial cognitive reserve (higher education levels exhibit faster cognitive decline at later stages of disease progression as they approach residential care (RC) placement.

Method: Two provincial administrative databases were used. One contained individuals' scores of cognitive functioning (assessed at 6- to 12-month intervals using the Standardized Mini-Mental State Examination, SMMSE, 2007–2014) and education level; the second (BC Ministry of Health Home and Community Care database, 2001–2014) contained individuals' RC placement; N = 10531.

Results: During 2.5–0.5 years prior to placement, SMMSE scores of patients with 0–8 years of education dropped slightly (M D 20.6 to 20.0), while patients with 9–12 years and 13+ years of education started higher (M D 21.8 and 21.4), but decreased faster and ended up lower (M D 19.5 and 18.8). Six-months prior to placement, SMMSE scores of all groups dropped almost 2 points.

Conclusions: Once cognitive reserve of more highly educated dementia patients is depleted and they approach RC placement, their cognitive functioning deteriorates faster. Finding effective interventions that maintain or enhance cognitive reserve may increase the time in the community for dementia patients.     

Acute transplantation of glial-restricted precursor cells into spinal cord contusion injuries: survival, differentiation, and effects on lesion environment and axonal regeneration

Transplantation of stem cells and immature cells has been reported to ameliorate tissue damage, induce axonal regeneration, and improve locomotion following spinal cord injury. However, unless these cells are pushed down a neuronal lineage, the majority of cells become glia, suggesting that the alterations observed may be potentially glially mediated. Transplantation of glial-restricted precursor (GRP) cells--a precursor cell population restricted to oligodendrocyte and astrocyte lineages--offers a novel way to examine the effects of glial cells on injury processes and repair. This study examines the survival and differentiation of GRP cells, and their ability to modulate the development of the lesion when transplanted immediately after a moderate contusion injury of the rat spinal cord. GRP cells isolated from a transgenic rat that ubiquitously expresses heat-stable human placental alkaline phosphatase (PLAP) were used to unambiguously detect transplanted GRP cells. Following transplantation, some GRP cells differentiated into oligodendrocytes and astrocytes, retaining their differentiation potential after injury. Transplanted GRP cells altered the lesion environment, reducing astrocytic scarring and the expression of inhibitory proteoglycans. Transplanted GRP cells did not induce long-distance regeneration from corticospinal tract (CST) and raphe-spinal axons when compared to control animals. However, GRP cell transplants did alter the morphology of CST axons toward that of growth cones, and CST fibers were found within GRP cell transplants, suggesting that GRP cells may be able to support axonal growth in vivo after injury.     

Enhancement of erythrocyte superoxide dismutase activity: effects on cellular oxidant defense

To delineate further the role of superoxide dismutase (SOD) in red blood cell (RBC) oxidant defense, normal human erythrocytes were osmotically lysed and resealed in the presence of varying concentrations of exogenous SOD. This resulted in a dose-dependent increase in SOD activity in the resealed erythrocytes while maintaining nearly normal RBC hemoglobin concentration (less than 10% decrease from the control value), cell volume, and cellular deformability. Surprisingly, a five- or ninefold increase in SOD activity yielded no additional protection against superoxide-generating drugs (phenazine methosulfate or menadione sodium bisulfite). No significant differences were observed between the control and SOD-loaded RBCs in O2-driven methemoglobin formation or generation of thiobarbituric acid-reactive substances. In contrast, RBCs with elevated SOD activity pretreated with sodium azide (to block catalase activity) or 1-chloro-2,4- dinitrobenzene (to deplete reduced glutathione, GSH) showed significantly enhanced methemoglobin generation in response to superoxide generating drugs. No differential response was noted between the control, control-resealed, and SOD-loaded RBCs to oxidants other than superoxide. Based on our results and other data, we conclude that elevated SOD activity may imbalance cellular oxidant defense, resulting in enhanced oxidation due to the accelerated generation of H2O2, the product of O2- dismutation. This effect is significantly exacerbated under conditions in which H2O2 catabolism is altered.     

Upregulation of the HLH Id gene family in neural progenitors and glial cells of the rat spinal cord following contusion injury.

Spinal cord injury (SCI) leads to a complex sequence of cellular responses, including astrocyte activation, oligodendrocyte death, and ependymal cell proliferation. Inhibitors of DNA binding (Id1, Id2, Id3) belong to a helix-loop-helix (HLH) gene family. Id genes have been implicated in playing a vital role in the proliferation of many cell types, including astrocytes and myoblasts. In the present study, the expression of Id family members in spinal cord after contusion injury was investigated by in situ hybridization. Id1, Id2, and Id3 mRNA expression was upregulated 5 mm rostral and caudal to the lesion center, and reached maximal levels 3 days after SCI. In addition, cell populations expressing Id1, Id2, and Id3 mRNA were maximally increased 3 days after SCI. The increase in Id2 and Id3 mRNA expression and Id2 and Id3 mRNA+ cells was still observed at 8 days. The Id mRNA expressing cells were phenotyped by combining immunostaining of cell-specific markers with in situ hybridization. Glial fibrillary acidic protein (GFAP)+ astrocytes were found to express all three Id mRNA, whereas S-100alpha+ astrocytes only expressed high levels of Id2 and Id3 mRNA. Cells having a neural progenitor morphology and the marker nestin appeared after SCI and they expressed Id1, Id2, and Id3 mRNA. Interestingly, some Rip+ oligodendrocytes located in the areas close to the central canal expressed Id3 mRNA after injury. In conclusion, Id genes are upregulated in a time-dependent manner in astrocytes, oligodendrocytes, and neural progenitor subpopulations after SCI, suggesting that they play major roles in cellular responses following SCI.