Predictors of improvement in diastolic function after transcatheter aortic valve implantation

Background

Aortic stenosis is associated with concentric left ventricle (LV) hypertrophy or remodeling resulting in impaired diastolic function and elevated left-sided filling pressure. We investigated the changes in LV geometry and LV filling hemodynamics, giving emphasis to parameters associated with changes in diastolic function after transcatheter aortic valve implantation (TAVI).

Methods

Comprehensive diastolic assessment was performed before and six months after TAVI in 70 patients with severe aortic stenosis. Patients with any degree of mitral stenosis or >mild left-sided valvular regurgitation were excluded.

Results

In the entire cohort six months after TAVI, LV end-diastolic diameter increased (44.1 ± 6 versus 45 ± 6 mm, P = 0.02), whereas LV mass and relative wall thickness (RWT) decreased (270.1 ± 76 versus 245.1 ± 75 g and 0.53 ± 0.15 versus 0.46 ± 0.1, respectively; P < 0.0001 for both). Lateral e′ increased (5.8 ± 2 versus 6.6 ± 3 cm/s, P = 0.03) and left atrium (LA) volume, E/e′ ratio, and systolic pulmonary pressure decreased (88.1 ± 30 versus 80 ± 28 cc, 18 ± 7.8 versus 16.3 ± 5.5, and 42.7 ± 14.9 versus 38.7 ± 12 mmHg, respectively; P < 0.05 for all), suggesting reduction in LA pressure. The improvement in LA volume and E/e′ was almost exclusively seen in patients with LV hypertrophy before TAVI (P < 0.05 both), as opposed to patients with concentric remodeling.

Conclusions

In our preliminary study, TAVI resulted in LV and LA reverse remodeling, and improved LV relaxation and LA filling pressure in patients with severe aortic stenosis and concentric hypertrophy. Patients with concentric remodeling at baseline seem to have limited improvement in LV diastolic function and filling pressure following TAVI, but larger clinical trials would be required to conclude if they have no improvement at all.     

Expression of the insulin-like growth factors and their receptors in adenocarcinoma of the colon

AIMS: To study changes in the expression of insulin-like growth factors (IGFs) and their receptors, as well as production of the IGF-I and IGF-II polypeptides, in adenocarcinoma of the colon. METHODS: Malignant tissue obtained at operation was used. Total RNA was extracted and specific IGF-I and IGF-II and their receptor mRNAs were measured by a solution hybridisation RNase protection assay. IGF-I and IGF-II polypeptides were measured by specific immunoassays. RESULTS: All normal tissues expressed IGF-II, IGF-I receptor, and IGF-II/mannose-6-phosphate (Man-6-P) receptor. IGF-I mRNA could not be detected but the polypeptide was present in small but equal amounts in normal and malignant tissue. IGF-II was expressed 40 times more abundantly in colonic tumours than in adjacent normal tissue and the concentration of the corresponding polypeptide was twice as high in the malignant tissue. IGF-I receptor expression was increased by a factor of 2.5 and IGF-II/Man-6-P receptor by a factor of 4. CONCLUSIONS: This study confirms that in adenocarcinoma of the human colon there is increased expression of IGF-I receptor and IGF-II. Furthermore, IGF-II/Man-6-P receptor message is increased and the increase in IGF-II message is accompanied by a doubling of the IGF-II protein in the tumour tissue compared with the adjacent normal tissue. These findings suggest that the IGF-II/Man-6-P receptor may also be involved in development of adenocarcinoma of the colon. There is rapidly accumulating evidence implicating the IGF system in the development of malignancy of the large bowel.     

A motor learning-based intervention to ameliorate freezing of gait in subjects with Parkinson’s disease

Freezing of gait (FOG) is an episodic gait disturbance that is commonly seen in Parkinson’s disease (PD). To date, treatment efficacy is limited. We tested the hypothesis that an intervention that utilizes motor learning provided through intensive cueing can alleviate this symptom. Fifteen subjects with PD suffering from FOG participated in a 6 week progressive motor learning program (three training sessions per week—open trial). A training session included FOG-provoking situations (e.g., turns). Prior to each presumed FOG provocation (e.g., just before a turn), rhythmic auditory stimulation (RAS) was elicited and the subject was trained to walk rhythmically, coordinate left–right stepping and to increase step size, utilizing the RAS cueing. Net training duration increased from week to week and secondary cognitive tasks while walking were added to increase FOG propensity. FOG symptom burden was assessed before, immediately, and 4 weeks after the training period. The mean number of FOG episodes (±SEM) per 10 m of walking in a standardized gait assessment decreased from 0.52 ± 0.29 in the pre-testing to 0.15 ± 0.04 in the post-testing (p < 0.05). The duration of FOG episodes decreased from 4.3 ± 2.1 to 2.6 ± 0.6 s (p < 0.05). Additional measures (e.g., FOG questionnaire, gait speed) varied in their responsiveness to the treatment. These effects were retained 4 weeks after the training. The results of this open label study support the possibility that a motor learning-based intervention is apparently effective in reducing FOG burden, suggesting that RAS can deliver ‘anti-FOG’ training.     

Oral N-acetylcysteine has a deleterious effect in acute iron intoxication in rats

Acute iron intoxication is associated with depletion of reduced glutathione in hepatocytes and changes in the glutathione system enzymes. We hypothesized that treatment with N-acetylcysteine (NAC), a glutathione reducing agent and an antioxidant, would reduce mortality in acute iron intoxication. We used a rat model to test this hypothesis. Male rats were assigned to 4 groups. Group 1 received 400 mg/kg elemental iron by oral gavage, group 2 received the same dose of iron followed by NAC, group 3 received NAC only, whereas group 4 received distilled water. Iron and liver transaminases in the blood, and glutathione system enzymes in the liver and erythrocytes were measured. Mortality in group 2 was significantly higher after 2, 6, and 24 hours compared with group 1 (P < .001). No deaths were observed in groups 3 and 4. Serum iron levels were significantly higher in group 2 rats compared to group 1 rats (P < .001). Hepatic and erythrocyte glutathione system enzymes were significantly lower among rats in group 2 compared to rats in group 1. The administration of NAC probably increased the absorption of iron through the gastrointestinal tract, causing higher serum iron levels with significant hepatic damage. These results indicate that in a rat model of acute iron intoxication, orally administered NAC may increase mortality.     

Is There a Need for Clinical Neuroskepticism?

Clinical neuroethics and neuroskepticism are recent entrants to the vocabulary of neuroethics. Clinical neuroethics has been used to distinguish problems of clinical relevance arising from developments in brain science from problems arising in neuroscience research proper. Neuroskepticism has been proposed as a counterweight to claims about the value and likely implications of developments in neuroscience. These two emergent streams of thought intersect within the practice of neurology. Neurologists face many traditional problems in bioethics, like end of life care in the persistent vegetative state, determination of capacity in progressive dementia, and requests for assisted suicide in cognition-preserving neurodegenerative disease (like amyotrophic lateral sclerosis). Neurologists also look to be at the forefront of downstream clinical applications of neuroscience, like pharmacological enhancement of mental life. At the same time, the practice of neurology, concerned primarily with the structure, function, and treatment of the nervous system, has historically fostered a kind of skeptical attitude toward its own subject matter. Not all problems that appear primarily neurological are primarily neurological. This disciplinary skepticism is generally clinical in orientation and limited in scope. The rise of interest in clinical neuroethics and in neuroskepticsim generally suggests a possible broader application. The clinical skepticism of neurology provides impetus for thinking about the appropriate role for skepticism in clinical areas of neuroethics. After a brief review of neuroskepticism and clinical neuroethics, a taxonomy of clinical neuroskepticism is offered and reasons why a stronger rather than weaker form of clinical neuroskepticism is currently warranted.