Are Canadian guidelines for cholesterol lowering in high-risk patients optimal?

Recent Canadian lipid guidelines recommend that all high-risk patients receive medication to reduce low density lipoprotein cholesterol (LDL-C) below 2.5 mmol/L. The recently published Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) studies compared strategies of cholesterol lowering with atorvastatin 80 mg versus pravastatin 40 mg. Atorvastatin halted the progression of atherosclerosis (whereas atherosclerosis progressed in the patients receiving pravastatin), and resulted in a 16% reduction in the primary composite end point (all-cause death, myocardial infarction, unstable angina, revascularization and stroke) compared with the pravastatin-treated group. In the PROVE IT trial, LDL-C was reduced by atorvastatin to 1.6 mmol/L and by pravastatin to 2.46 mmol/L. Although lower LDL-C levels are one explanation for the improved outcomes with atorvastatin, pleiotropic differences of the two statins, such as their effects on inflammation and coagulation, cannot be excluded. Until trials are completed that compare outcomes from LDL-C lowering to different targets with the same statin, it is premature to recommend changes to the current Canadian guidelines. However, future recommendations may suggest much lower LDL-C targets than those currently recommended.     

Interval training in elderly men increases both heart rate variability and baroreflex activity

Abstract Aims Autonomic nervous system activity decreases continuously with age and appears to be a powerful predictor of disease and death. Attempts are thus made to reactivate autonomic drive with the intent of improving health. Methods We assessed maximal oxygen consumption (VO_2max), auto- nomic nervous system activity by heart rate variability (HRV) analysis and spontaneous cardiac baroreflex activity (SBR) in eleven elderly men (73.5±4.2 years) before and after a 14-week program of intensive cycloergometer interval training. The standard HRV indices were calculated using time domain (mean RR, PNN50, RMSSD, SDNN, SDANN and SDNNIDX), and Fourier transform (total power, ULF,VLF, LF, LFnu, HF, HFnu and LF/HF) analyses of 24-hour, daytime and nighttime Holter recordings. The SBR was calculated from 15-minute recordings of spontaneous blood pressure and RR interval variations using the sequence (slope, slSBR) and cross-spectral (SBR_HF and SBR_LF) methods. Results After the training period,VO_2max increased by 18.6 % (26.8±4.4 to 31.8±5.2 ml · kg^–1 · min^–1, p<0.01). The nocturnal parasympathetic indices of HRV increased (PNN50: 3.05±2.21 to 5.00±2.87%, RMSSD: 29.1±7.6 to 38.8±10.9 ms, HF: 117±54 to 194±116 ms²/Hz, all p<0.05) as did the SBR indices (slSBR: 7.0±1.8 to 9.8±2.1 ms·mmHg^–1, p<0.01; SBR_HF: 6.9±2.2 to 10.5±3.7 ms ·mmHg^–1, p<0.05; SBR_LF: 5.3±2.3 to 6.9±3.1 ms ·mmHg^–1, p=0.22). Conclusion Intensive endurance training in elderly men enhanced parasympathetic parameters of HRV and, interestingly, of SBR. Physiological mechanisms and long-term clinical effects on health status should be further investigated.     

FDG-PET measurement is more accurate than neuropsychological assessments to predict global cognitive deterioration in patients with mild cognitive impairment

The accurate prediction, at a pre-dementia stage of Alzheimer's disease (AD), of the subsequent clinical evolution of patients would be a major breakthrough from both therapeutic and research standpoints. Amnestic mild cognitive impairment (MCI) is presently the most common reference to address the pre-dementia stage of AD. However, previous longitudinal studies on patients with MCI assessing neuropsychological and PET markers of future conversion to AD are sparse and yield discrepant findings, while a comprehensive comparison of the relative accuracy of these two categories of measure is still lacking. In the present study, we assessed the global cognitive decline as measured by the Mattis scale in 18 patients with amnestic MCI over an 18-month follow-up period, studying which subtest of this scale showed significant deterioration over time. Using baseline measurements from neuropsychological evaluation of memory and PET, we then assessed significant markers of global cognitive change, that is, percent annual change in the Mattis scale total score, and searched for the best predictor of this global cognitive decline. Altogether, our results revealed significant decline over the 18-month follow-up period in the total score and the verbal initiation and memory-recall subscores of the Mattis scale. The percent annual change in the total Mattis score significantly correlated with age and baseline performances in delayed episodic memory recall as well as semantic autobiographical and category word fluencies. Regarding functional imaging, significant correlations were also found with baseline PET values in the right temporo-parietal and medial frontal areas. Age and right temporo-parietal PET values were the most significant predictors of subsequent global cognitive decline, and the only ones to survive stepwise regression analyses. Our findings are consistent with previous works showing predominant delayed recall and semantic memory impairment at a pre-dementia stage of AD, as well as early metabolic defects in the temporo-parietal associative cortex. However, they suggest that only the latter predictor is specifically and accurately associated with subsequent cognitive decline in patients with MCI within 18 months of first assessment.     

Religious practice and psychological distress: the importance of gender, ethnicity and immigrant status

The present study examined the relationship between religious practice and psychological distress in a culturally diverse urban population to explore how religious affiliation, gender, ethnicity, and immigrant status affect this relationship. Data were drawn from a study of health care utilization in Montreal. A stratified community sample of 1485 yielded four religious groups: Protestant (n = 205), Catholic (813), Jewish (201), and Buddhist (150), and a group with no declared religion (116). The sample was composed of five ethnocultural groups: Anglophone Canadian-born, Francophone Canadian-born, Afro-Caribbean, Vietnamese, and Filipino immigrants. Psychological distress was assessed with the 12-item version of the General Health Questionnaire (GHQ). Religious involvement was measured with three items: 1) declared religion; 2) frequency of attendance at religious meetings; and 3) frequency of religious rituals performed at home. Multiple regression models examined the relationship of religious practice to distress, controlling for sociodemographic variables including ethnicity. Overall, attendance at religious services was associated with a lower GHQ score. Attendance at religious services also was inversely related to psychological distress for females, Protestants, Catholics, Filipinos, and Afro-Caribbeans; but not for males, Buddhists or Jews. Religious practice at home was not associated with level of distress for any group. The 'no declared religion' group had the highest mean GHQ score of all the groups. Results confirm the association between attendance at religious services and lower levels of distress, but reveal ethnospecific and gender effects indicating the need to understand the impact of religious practice on mental health in social and cultural context.     

Histopathological effects of delayed reperfusion after middle cerebral artery occlusion in the anesthetized baboon

In patients with middle cerebral artery (MCA) territory stroke, attempts to recanalize the brain are currently being extended beyond the classic 3-h time window. Mechanical thrombectomy is particularly attractive as it may carry lesser risks of severe hemorrhagic transformation than thrombolysis. However, whether late reperfusion per se promotes hemorrhagic transformation and increases infarct volume as compared to permanent occlusion is unclear. There is no study of the histopathologic sequelae of late reperfusion following MCA occlusion (MCAo) in the non-human primate. Five young adult baboons completed a specially designed protocol of 20-h MCAo (under etomidate anaesthesia), followed by 4-week survival and finally perfusion-fixation. Infarct volume was measured histologically using validated stereological methods. The results were compared to our previously published series of 6 h and permanent MCAo performed with identical experimental and post mortem procedures. An infarct was present in each baboon, consistently involving the caudate head, internal capsule and putamen; the adjacent inferior frontal cortex was involved in one subject. Infarct volume was significantly larger than with 6 h MCAo, as expected, but did not differ from permanent MCAo. There was no evidence of hemorrhage around the infarcted area in any animal. We found that following a 20 h ischemic episode, the infarct volume was similar to that found with permanent occlusion, with no evidence of hemorrhagic transformation. Cautiously extrapolating to the human situation, our findings suggest that even late mechanical recanalization may not promote brain damage and could be considered in selected cases.     

Effect of intrastriatal 6-OHDA lesion on dopaminergic innervation of the rat cortex and globus pallidus

The present study examined in the rat the effect of a partial lesion of the nigrostriatal dopaminergic pathway induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA), on the dopaminergic innervation of the cortex and the globus pallidus as revealed using tyrosine hydroxylase (TH) immunoreactivity. Twenty-eight days after unilateral injection of 6-OHDA into the dorsal part of the striatum, TH-positive fiber density was reduced by 41% in the dorsal and central part of the structure, and was accompanied by a retrograde loss of 33% of TH-positive neurons in the substantia nigra (SN), while the ventral tegmental area was completely spared. In the SN, TH-positive cell loss was most severe in the ventral part of the structure (-55%). In the same animals, a substantial loss of TH-positive fibers was evident in the dorsal part of the globus pallidus, and involved both thick fibers of passage and thin varicose terminal axonal branches. In the cortex, a loss of TH-positive fibers was prominent in the cingulate area, moderate in the motor area and less affected in the insular area, while the noradrenergic innervation revealed using dopamine-beta-hydroxylase immunoreactivity was preserved in all of these cortical subregions. These results demonstrate that the intrastriatal 6-OHDA lesion model in rats produces a significant loss of dopaminergic axons in extrastriatal structures including the pallidum and cortex, which may contribute to functional sequelae in this animal model of Parkinson's disease.     

Phenomenology: a scientific approach to lived experiences

Phenomenology is a philosophical current which intends to observe and describe the meaning attributed to an experience from the consciousness of the person who is living it. While it can be applied to different domains, especially to human care it describes subjective phenomenon such as suffering or quality of life. It constitutes as a real discipline, with its epistemology, its specific data (the individual's narration), its method of analysis to find the speech units of significance, and collaboration between researcher and participant (who becomes a co-researcher). Validity of the method is defined by the fact that the phenomenon becomes intelligible. In the representation of the disease and of the patient, the method is close to ethical principles like respect of autonomy and optimization of quality of life.     

The potential for utilizing the "mirror neurone system" to enhance recovery of the severely affected upper limb early after stroke: a review and hypothesis

Recovery of upper limb movement control after stroke might be enhanced by repetitive goal-directed functional activities. Providing such activity is challenging in the presence of severe paresis. A possible new approach is based on the discovery of mirror neurons in the monkey cortical area F5, which are active both in observing and executing a movement. Indirect evidence for a comparable human "mirror neurone system" is provided by functional imaging. The primary motor cortex, the premotor cortex, other brain areas, and muscles appropriate for the action being observed are probably activated in healthy volunteers observing another's movement. These findings raise the hypothesis that observation of another's movement might train the movement execution system of stroke patients who have severe paresis to bring them to the point at which they could actively participate in rehabilitation consisting of goal-directed activities. The point of providing an observation therapy would be to facilitate the voluntary production of movement; therefore, the condition of interest would be observation with intent to imitate. However, there is as yet insufficient evidence to enable the testing of this hypothesis in stroke patients. Studies in normal subjects are needed to determine which brain sites are activated in response to observation with intent to imitate. Studies in stroke subjects are needed to determine how activation is affected after damage to different brain areas. The information from such studies should aid identification of those stroke patients who might be most likely to benefit from observation to imitate and therefore guide phase I clinical studies.