Marc Stefan Dawid-Milner

Acetylcholinesterase inhibitors and the risk of hip fracture in Alzheimer's disease patients: A case-control study

Recent studies have reported the presence of acetylcholine (ACh) receptor subtypes in bone tissue, and have demonstrated that inhibition of the ACh receptors has negative effects on bone mass and fracture healing capacity. However, little is known about the potential clinical effects that increased ACh signaling might have on bone. Accordingly, this study was designed to determine whether the use of acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate ACh receptors and are used to treat Alzheimers disease (AD), is associated with a decreased risk of hip fracture in AD patients. To accomplish this objective, a case‐control analysis was performed using the AD population, aged above 75 years, based in the local health area of the Carlos Haya Hospital, in Malaga, Spain. The cases were 80 AD patients that suffered a hip fracture between January 2004 and December 2008. The controls were 2178 AD patients without hip fracture followed at our health care area during the same period of time. Compared with patients who did not use AChEIs, the hip fracture adjusted odds ratio (OR) for users of AChEIs was 0.42 (95% confidence interval [CI], 0.24–0.72), for users of rivastigmine was 0.22 (95% CI, 0.10–0.45), and for users of donepezil was 0.39 (95% CI, 0.19–0.76). Data were adjusted for the following parameters: body mass index, fall risk, smoking habits, cognition, dependence, degree of AD, comorbidity score, treatment with selective serotonin reuptake inhibitors, age, and gender. Our data suggests that use of AChEIs donepezil and rivastigmine is associated with a reduced risk of fractures in AD patients. Many elderly patients with AD disease who are at risk of developing osteoporosis may potentially benefit from therapy with the AChEIs donepezil and rivastigmine.

Laryngeal effects of stimulation of rostral and ventral pons in the anaesthetized rat

In order to study the importance of two pontine regions modulating laryngeal resistance, electrical current or microinjections of glutamate (10-30 nl, 1-3 nmol) were made into the pontine parabrachial complex and the A5 region in spontaneously breathing anaesthetized rats. Two distinct patterns of laryngeal and respiratory responses were elicited. An increase of subglottal pressure was accompanied with an expiratory facilitatory response consisted of a decrease in both respiratory rate and phrenic nerve activity. A decrease of subglottal pressure was accompanied with an inspiratory facilitatory response consisted of an increase in both respiratory rate and phrenic nerve activity. The modification of laryngeal calibre occurred during both respiratory phases in most cases. The concomitant cardiovascular changes of these responses were also analyzed. Controls using guanethidine to block autonomic responses which might interact with respiratory control were also made. Histological analysis of stimulation sites showed a topographical organization of these responses: laryngeal constriction was evoked from Kölliker-Fuse, medial parabrachial nuclei and A5 region, whilst the laryngeal dilation was evoked from the lateral parabrachial nucleus.

Bilateral brain reorganization with memantine and constraint-induced aphasia therapy in chronic post-stroke aphasia: An ERP study.

Changes in ERP (P100 and N400) and root mean square (RMS) were obtained during a silent reading task in 28 patients with chronic post-stroke aphasia in a randomized, double-blind, placebo-controlled trial of both memantine and constraint-induced aphasia therapy (CIAT). Participants received memantine/placebo alone (weeks 0-16), followed by drug treatment combined with CIAT (weeks 16-18), and then memantine/placebo alone (weeks 18-20). ERP/RMS values (week 16) decreased more in the memantine group than in the placebo group. During CIAT application (weeks 16-18), improvements in aphasia severity and ERP/RMS values were amplified by memantine and changes remained stable thereafter (weeks 18-20). Changes in ERP/RMS occurred in left and right hemispheres and correlated with gains in language performance. No changes in ERP/RMS were found in a healthy group in two separated evaluations. Our results show that aphasia recovery induced by both memantine alone and in combination with CIAT is indexed by bilateral cortical potentials.

Parabrachial complex glutamate receptors modulate the cardiorespiratory response evoked from hypothalamic defense area

To characterize the possible role of glutamate in the interaction between Hypothalamic Defense Area (HDA) and Parabrachial complex (PBc) nuclei, cardiorespiratory changes were analyzed in response to electrical stimulation of the HDA (1 ms pulses, 30-50 μA given at 100 Hz for 5s) before and after the microinjection of the nonspecific glutamate receptor antagonist kynurenic acid (50 nl, 5 nmol), NMDA receptor antagonist MK-801 (50 nl, 50 nmol), non-NMDA receptor antagonist CNQX (50 nl, 50 nmol) or metabotropic glutamate receptor antagonist MCPG (50 nl, 5 nmol) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (p<0.001) due to a decrease in expiratory time (p<0.01). The respiratory response was accompanied by a pressor (p<0.001) and a tachycardic response (p<0.001). Kynurenic acid within the lateral parabrachial region (lPB) abolished the tachycardia (p<0.001) and decreased the magnitude of blood pressure response (p<0.001) to HDA stimulation. Similarly, the magnitude of the tachycardia and the pressor response was decreased after the microinjection of MK-801 (p<0.01 and p<0.001, respectively) and CNQX (p<0.05 in both cases) into the lPB. Kynurenic acid microinjection in this region produced an inhibition of the tachypnea (p<0.001) to HDA stimulation but the respiratory response persisted unchanged after MK-801 or CNQX microinjection into the lPB. Kynurenic acid within the medial parabrachial region (mPB) abolished the tachycardia (p<0.01) and decreased the magnitude of the pressor response (p<0.001) to HDA stimulation. MK-801 and CNQX microinjection in this region decreased the magnitude of the tachycardia (p<0.05, in both cases) and pressor response (p<0.05, in both cases). The respiratory response evoked by HDA stimulation was not changed after the microinjection of kynurenic acid, MK-801 or CNQX within the mPB. No changes were observed in the cardiorespiratory response evoked to HDA stimulation after MCPG microinjection within lPB and mPB. These results indicate that glutamate PBc receptors are involved in the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

Role of the parabrachial complex in the cardiorespiratory response evoked from hypothalamic defense area stimulation in the anesthetized rat.

To analyze the role of parabrachial complex (PBc) in the modulation of cardiorespiratory response evoked from the hypothalamic defense area (HDA), cardiorespiratory changes were analyzed in spontaneously breathing anesthetised rats in response to electrical stimulation of the HDA (1 ms pulses, 30-50 microA, 100 Hz for 5 s) before and after the microinjection of muscimol (50 nl, 0.25 nmol, 5 s) within the PBc. HDA stimulation evoked an inspiratory facilitatory response, consisting of an increase in respiratory rate (p<0.001) due to a decrease in expiratory time (p<0.01). The respiratory response was accompanied by a pressor (p<0.001) and a tachycardic (p<0.001) response. Muscimol microinjection within the lateral parabrachial region (lPB) abolished the respiratory response to HDA stimulation (p<0.01) and decreased the pressor response (p<0.05). Muscimol within the medial parabrachial region and Kölliker-Fuse (mPB-KF) decreased the magnitude of the pressor (p<0.01) and tachycardic (p<0.05) responses to HDA stimulation. The respiratory response persisted unchanged. Finally, extracellular recording of putative neurons from these regions were obtained during HDA stimulation to confirm functional interaction between HDA and parabrachial regions. 105 pontine cells were recorded during HDA stimulation, 57 from the lPB and 48 from the mPB-KF. In mPB-KF 34/48 (71%) and in lPB 38/57 (67%) cells were influenced from HDA. The results indicate that neurons from different regions of the PBc have an important function in mediating the cardiorespiratory response evoked from the HDA. The possible mechanisms involved in these interactions are discussed.

Neurons of the A5 region are required for the tachycardia evoked by electrical stimulation of the hypothalamic defence area in anaesthetized rats.

•  What is the central question of this study? As the parabrachial complex plays a role in the cardiorespiratory response evoked from the hypothalamic defence area (pressor response and tachycardia) and the A5 region is involved in the responses evoked from the parabrachial complex, a possible interaction between the hypothalamic defence area and A5 is suggested. Accordingly, the present study was carried out to assess this hypothesis in rats. •  What is the main finding and its importance? The neuromorphological, neuropharmacological and electrophysiological results of our study demonstrate, for the first time, that the A5 region is an important component of those brainstem pathways known to be involved in mediating the autonomic changes associated with the electrically evoked defence response.

Autonomic dysfunction elicited by a medulla oblongata injury after fourth ventricle tumor surgery in a pediatric patient

We report the case of a 9-year-old male patient with a recurrent fourth ventricle anaplastic ependymoma who developed severe arterial hypertension and blood pressure lability during and after surgery. A punctual bilateral lesion located within mid dorsal medulla oblongata caused by both infiltration and surgical resection was observed in postoperative MRI. Three years later, the patient remained neurologically stable but the family referred the presence of a chronic tachycardia as well as palpitations and sweating with flushing episodes related to environmental stress. On autonomic evaluation, an increase in sympathetic outflow with tachycardia together with orthostatic hypotension caused by baroreceptor reflex dysfunction was observed. We postulate that a bilateral injury to both nuclei of the solitary tract may have caused central dysautonomia.

Colour Video Segmentation for the Quantification of Sweat Dynamic Function

Our main objective is design and develop a system that assesses sudomotor function with spatial and temporal resolution through digital image processing techniques. Its evaluation has become significant in the diagnosis of several nerve diseases. The current methods to evaluate post-ganglionic sudomotor function are not very successful because they are too expensive or they do not give enough information. It will be desirable to achieve useful results with a low cost approach. In order to this, it can be used a pH indicator on the skin of patient that changes colour when it comes in contact with sweat and a digital image processing algorithm to quantify it. The sudomotor function of more than 20 patients, with a wide range of profiles, has been tested. There is a high correlation between our results and those of others kinds of sweat tests. From all of this it can conclude that it is possible to implement an evaluation system for sudomotor function using digital image processing with a low cost solution.