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Supplementation of vitamin E may attenuate skeletal muscle immobilization atrophy.

The aim of this study was to investigate whether oxidative stress contributes to the development of atrophy in immobilized muscles, and, under this assumption, whether the administration of an antioxidant has beneficial effects to attenuate immobilization atrophy. One hindlimb of rats was immobilized for eight days, the contralateral leg served as control. One experimental group was supplemented with vitamin E. In the soleus muscle, the glutathione content as an indicator for oxidative stress was measured, and muscle fiber diameters were evaluated to estimate muscle atrophy. The biochemical results indicate no pronounced oxidative stress in the immobilized muscles and even less oxidative stress in the vitamin E supplemented muscles (with and without immobilization). Eight days of immobilization lead to a 35% atrophy, while with vitamin E the muscles atrophied only by 12%. This difference can be attributed to the action of vitamin E as a scavenger for free radicals and, on the other hand, to an atrophy promoting effect of oxidative stress. Oxidative stress is hypothesized to exist during the initial phase, but to disappear after some days of immobilization. It is suggested that oxidative stress plays a role in initiating muscle atrophy, and supplementation of vitamin E prior to and during the early phase of immobilization is recommended. Moreover, such may also be useful during remobilization to avoid additional oxidative stress with rehabilitative exercise.

Animals↗

Action of topical thyroid hormone analogues on glucocorticoid-induced skin atrophy in mice.

Previously we demonstrated the stimulation of collagen synthesis in triiodothyroacetic acid (TRIAC)-topically treated human and mice. In the present study, we have evaluated the dose response effect of thyroid hormone (TH) analogues and tretinoin on glucocorticoid-induced skin atrophy in a haired mouse model. For this investigation, we treated haired mice twice daily for 7 days with various topically administered doses of TRIAC, triiodothyronine-sodium salt (T(3)-Na), diiodothyroacetic acid (DIAC), 3,5-diiodothyropropionic acid (DITPA), and tretinoin with 0.2 mM betamethasone17-valerate (BM), or with the vehicle as a control group. We also investigated a combination of commercial betamethasone dipropionate (BD) 0.05% cream and various doses of TRIAC on mouse skin. TRIAC was able to reverse the skin atrophy by 25% in a daily dose of 1 nmol/cm(2) in the presence of 0.2 mM BM (p < 0.05). Neither other TH analogues nor TRIAC in lower and higher concentrations had a significant inhibitory effect on dermal atrophy (p > 0.05). A combination of 0.2 mM BM and 10 nmol/cm(2) TRIAC was able to prevent dermal atrophy by 18%. The addition of TRIAC to 0.05% BD cream in a final concentration of 0.1% was able partially to reverse the dermal atrophy by 15% (p < 0.05). TRIAC alone in a concentration of 1,000 nmol/cm(2) stimulated dermal proliferation by 34% (p < 0.05). Other TH analogues alone had no stimulatory effect on dermal proliferation. Tretinoin 0.8 mM was able to inhibit dermal atrophy by 20% (p < 0.05) and had an effect on dermal thickness of 85% (p < 0.05). However, severe side effects with edema, erythema, and scaling were commonly observed in all tretinoin-treated mouse skin, which could partly explain the increase in dermal thickness. In contrast, no skin side effects were observed after treatment with TRIAC. This study indicates that TRIAC may have a therapeutic effect on BM-induced dermal atrophy in mouse skin and a direct stimulatory effect on dermal proliferation when given alone.

Acetates↗

Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study.

BACKGROUND: Previous studies suggested that low concentrations of folate in the blood are related to poor cognitive function, dementia, and Alzheimer disease-related neurodegeneration of the brain. OBJECTIVE: Our aim was to determine whether serum folate is inversely associated with the severity of atrophy of the neocortex. DESIGN: Nutrients, lipoproteins, and nutritional markers were measured in the blood of 30 participants in the Nun Study from one convent who later died when they were 78-101 y old (mean: 91 y). At autopsy, several neuropathologic indicators of Alzheimer disease were determined, including the degree of atrophy of 3 lobes of the neocortex (frontal, temporal, and parietal) and the number of neocortical Alzheimer disease lesions (ie, senile plaques and neurofibrillary tangles) as assessed by a neuropathologist. RESULTS: The correlation between serum folate and the severity of atrophy of the neocortex was -0.40 (P = 0.03). Among a subset of 15 participants with significant numbers of Alzheimer disease lesions in the neocortex, the correlation between folate and atrophy was -0.80 (P = 0.0006). Atrophy may be specific to low folate because none of the 18 other nutrients, lipoproteins, or nutritional markers measured in the blood had significant negative correlations with atrophy. CONCLUSIONS: Among elderly Catholic sisters who lived in one convent, ate from the same kitchen, and were highly comparable for a wide range of environmental and lifestyle factors, low serum folate was strongly associated with atrophy of the cerebral cortex. Definitive evidence for this relation and its temporal sequence awaits the findings of other studies.

Aged↗

Pathological study of spinal cord atrophy in multiple sclerosis suggests limited role of local lesions.

Imaging studies in multiple sclerosis have shown that spinal cord atrophy correlates with clinical disability. The pathological substrate of atrophy has not as yet been investigated adequately. In order to determine the cause of spinal cord atrophy in multiple sclerosis, five different sections of the spinal cord were examined histopathologically in 33 controls and 55 multiple sclerosis cases. In the multiple sclerosis cases in each section the total lesion load and the cross-sectional area of the cord were measured. Multiple regression models were estimated, controlling for sex, age, duration of the disease and location of the cord sections. The multiple sclerosis cords were found to be significantly smaller than the controls. The duration of the disease played the most important role in determining cord atrophy. The degree of atrophy varied in different parts of the cord. Individual lesions played a minor role in local atrophy. Our findings suggest that axonal degeneration, possibly caused by the cumulative number of lesions in the brain and cord, or an alternative atrophic process, is responsible for spinal cord atrophy in multiple sclerosis, rather than tissue loss within individual lesions.

Adult↗

Clinical deficits correlate with regional cerebral atrophy in progressive supranuclear palsy.

Most cerebral imaging studies of patients with progressive supranuclear palsy (PSP) have noted subtle atrophy, although the full extent of atrophy and any correlates to clinical features have not been determined. We used voxel-based morphometry analysis of grey matter, white matter and CSF on MRI brain scans to map the statistical probability of regional tissue atrophy in 21 patients with PSP, 17 patients with Parkinson's disease and 23 controls. PSP and Parkinson's disease cohorts were selected to approximate the mid-stages of their respective disease courses. Where regions of significant tissue atrophy were identified in a disease group relative to controls, the probability of tissue loss within those regions was correlated with global indices of motor disability, and behavioural and cognitive disturbance for that disease group. Minimal regional atrophy was observed in Parkinson's disease. PSP could be distinguished from both controls and Parkinson's disease by symmetrical tissue loss in the frontal cortex (maximal in the orbitofrontal and medial frontal cortices), subcortical nuclei (midbrain, caudate and thalamic) as well as periventricular white matter. For PSP, motor deficits correlated with atrophy of the caudate and motor cingulate, while behavioural changes related to atrophy in the orbitofrontal cortex and midbrain. These data suggest that intrinsic neurodegeneration of specific subcortical nuclei and frontal cortical subregions together contribute to motor and behavioural disturbances in PSP and differentiate this disorder from Parkinson's disease within 2-4 years of symptom onset.

Aged↗

Helicobacter pylori infection and gastric atrophy: risk of adenocarcinoma and squamous-cell carcinoma of the esophagus and adenocarcinoma of the gastric cardia.

BACKGROUND: An inverse association between Helicobacter pylori infection and esophageal adenocarcinoma has been reported that may be attributed to reduced acidity from inducing atrophic gastritis and from producing ammonia. We examined associations between H. pylori infection, gastric atrophy, and the risk of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and gastric cardia adenocarcinoma in a large population-based case-control study in Sweden. METHODS: Self-reported data were obtained during interviews, and serum was collected from 97 patients with incident esophageal adenocarcinoma, 85 patients with incident esophageal squamous-cell carcinoma, 133 patients with incident gastric cardia adenocarcinoma, and 499 randomly selected control subjects. Serum antibodies against whole H. pylori cell-surface antigens (HP-CSAs) and cytotoxin-associated gene A (CagA) antigens were assessed by an IgG enzyme-linked immunosorbent assay and immunoblotting, respectively. Gastric atrophy was assessed by serum levels of pepsinogen I. Multivariable logistic regression with adjustment for potential confounding factors was used to evaluate associations. RESULTS: H. pylori infection, assayed by HP-CSA or CagA antibodies, was statistically significantly associated with a reduced risk for esophageal adenocarcinoma (for HP-CSA antibodies, odds ratio [OR] = 0.3, 95% confidence interval [CI] = 0.2 to 0.6; for CagA antibodies, OR = 0.5, 95% CI = 0.3 to 0.8; for both, OR = 0.2, 95% CI = 0.1 to 0.5). Gastric atrophy was not associated with the risk for esophageal adenocarcinoma (OR = 1.1, 95% CI = 0.5 to 2.5). Serum CagA antibodies and gastric atrophy were associated with an increased risk for esophageal squamous-cell carcinoma (OR = 2.1, 95% CI = 1.1 to 4.0, and OR = 4.3, 95% CI = 1.9 to 9.6, respectively). The risk of gastric cardia adenocarcinoma was not associated with H. pylori infection. However, gastric atrophy was associated with an increased risk for gastric cardia adenocarcinoma (OR = 4.5, 95% CI = 2.5 to 7.8). CONCLUSIONS: Infection with H. pylori may reduce the risk of esophageal adenocarcinoma, but it is unlikely to do so by atrophy-reduced acidity. Gastric atrophy and infection with CagA-positive strains of H. pylori may increase the risk for esophageal squamous-cell carcinoma.

Adenocarcinoma↗

Polymorphism of tumor necrosis factor-beta and alcohol dehydrogenase genes and alcoholic brain atrophy in Japanese patients.

BACKGROUND: Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. Many inflammatory cytokines such as tumor necrosis factor (TNF) are produced rapidly in the brain by experimental or clinical injury. METHOD: To investigate whether genetic polymorphism of TNF was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the TNF-beta genes in 72 male alcoholics. Computed tomography was used to determine the severity of brain atrophy. RESULTS: Digestion with NcoI and MspI after polymerase chain reaction amplification showed that the TNFB1 allele frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (chi2 = 10.20, p = 0.0034). A multivariate analysis that included age, total alcohol intake, ADH2 genotype, and TNF-beta genotype showed that the ADH21/21 genotype and TNFB1/B1 genotype are independently associated with alcoholic brain atrophy. These findings suggest that the TNFB1 allele may be associated with alcoholic brain atrophy.

Adult↗

Correlation between a disc hemorrhage and peripapillary atrophy in glaucoma patients with a unilateral disc hemorrhage.

PURPOSE: To investigate the correlation between a disc hemorrhage and peripapillary atrophy in glaucoma patients with a unilateral disc hemorrhage. METHODS: The 44 glaucoma patients (7 with primary open-angle glaucoma and 37 with normal-tension glaucoma) with a unilateral disc hemorrhage from June 1997 to November 2002 were selected randomly and included sequentially. The topographic measurements were performed using Heidelberg Retina Tomograph (HRT) within 3 months of detecting the disc hemorrhage. The zone beta parameters of the peripapillary atrophy were analyzed by the Atrophy Zone Analysis software. The intraocular pressure, refractive error, visual field parameters, and optic disc parameters were compared between both eyes. Univariate and multivariate regression analysis were performed. RESULTS: The area, angular and radial extent of the zone beta, and the ratio of the zone beta area to the disc area were significantly greater in the hemorrhagic eyes than in the contralateral eyes (P < 0.001). The prevalence of peripapillary atrophy was significantly higher in the hemorrhagic eyes (84%) than in the contralateral eyes (66%) (P = 0.034, chi2 test). The rim area and the rim volume of the hemorrhagic eyes were significantly smaller than those of the contralateral eyes (P = 0.02, < 0.001, respectively). In multivariate regression analysis, the peripapillary atrophy area was the independent significant factor associated with disc hemorrhage (P = 0.03, Odds Ratio = 1.51). The refractive error, intraocular pressure, Mean Deviation (MD), and Corrected Pattern Standard Deviation (CPSD) of the visual fields in both eyes were similar. CONCLUSION: The area and extent of the peripapillary atrophy was significantly greater and more prevalent in the eyes with a disc hemorrhage than in the contralateral control eyes. Peripapillary atrophy is closely associated with a disc hemorrhage in glaucoma patients irrespective of small neuroretinal rim area and volume.

Aged↗

Progressive hippocampal and extrahippocampal atrophy in drug resistant epilepsy.

PURPOSE OF REVIEW: This article reviews recent experimental and clinical evidence for seizure-related progressive brain damage and discusses possible mechanisms of ongoing brain atrophy in epilepsy. RECENT FINDINGS: Experimental data indicate that seizures induce brain plasticity that may result in either damage or protection. Brief seizures or status epilepticus may promote resistance to additional damage but also induce cumulative neuronal loss and increase susceptibility to network synchronization. Some experimental studies indicated that, following the initial damage caused by status epilepticus, further brief seizures may not produce significant continuing neuronal loss and hippocampal atrophy, whereas other studies showed the contrary. There is recent evidence that progressive damage and atrophy may occur after an acute insult but are not directly associated with recurrent seizures. Clinical research data continue to show discrepancies regarding whether ongoing seizures cause progressive atrophy. Some cross-sectional and longitudinal magnetic resonance imaging studies in patients with partial epilepsies have shown progressive hippocampal and extrahippocampal atrophy, the severity of which correlated with the duration of epilepsy, seizure frequency, or lifetime seizure number, whereas others have failed to show a clear association. SUMMARY: Experimental data indicate that epileptogenesis in developing brain may not require significant neuronal loss, which is in keeping with clinical observations that progressive cognitive and behavioural impairment may occur in patients with no detectable brain atrophy. A better understanding of why, when and how progressive brain atrophy occurs will lead to better clinical management, earlier surgical intervention when necessary and, ultimately, prevention of epileptogenesis.

Anticonvulsants↗

Cerebral atrophy as predictor of cognitive function in old, community-dwelling individuals.

OBJECTIVES: The impact of cortical and subcortical atrophy on cognitive function was examined in a sample of older community-dwelling men and women. MATERIAL AND METHODS: Magnetic resonance imaging was performed on a sample of 129 individuals [age: 68.4 +/- 3.6 years (mean +/- SD), range 64-74 years, 64 women and 65 men, Mini-Mental State Examination scores above 23] to assess cortical and subcortical atrophy. Participants also performed a number of cognitive tasks, and the measures of atrophy were used to predict performance in these tasks. RESULTS: In men, frontal cortical atrophy predicted worse performance in word fluency and the Stroop test, and occipital cortical atrophy was associated with poor performance in motor speed. In women, poor performance in motor speed was associated with subcortical atrophy at the level of the caudate nucleus. CONCLUSION: Atrophy in certain areas was associated with poor performance in specific cognitive tasks, although the amount of explained variance was rather limited in this quite homogeneous sample.

Aged↗

Mapping the onset and progression of atrophy in familial frontotemporal lobar degeneration.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) may be inherited as an autosomal dominant disease. Studying patients "at risk" for developing FTLD can provide insights into the earliest onset and evolution of the disease. METHOD: We carried out approximately annual clinical, MRI, and neuropsychological assessments on an asymptomatic 51 year old "at risk" family member from a family with FTLD associated with ubiquitin-positive and tau-negative inclusion bodies. We used non-linear (fluid) registration of serial MRI to determine areas undergoing significant regional atrophy at different stages of the disease. RESULTS: Over the first 26 months of the study, the patient remained asymptomatic, but subsequently developed progressive speech production difficulties, and latterly severe orofacial dyspraxia, dyscalculia, frontal executive impairment, and limb dyspraxia. Regional atrophy was present prior to the onset of symptoms, and was initially centred on the left dorsolateral prefrontal cortex and the left middle frontal gyrus. Latterly, there was increasing asymmetric left frontal and parietal atrophy. Imaging revealed excess and increasing global atrophy throughout the study. Neuropsychological evaluation revealed mild intellectual impairment prior to the onset of these clinical symptoms; frontal executive and left parietal impairment subsequently emerged, culminating in widespread cognitive impairment. Fluid registered MRI allowed the emerging atrophy patterns to be delineated. CONCLUSION: We have demonstrated the onset and progressive pattern of in vivo atrophy in familial FTLD using fluid registered MRI and correlated this with the clinical features. Fluid registered MRI may be a useful technique in assessing patterns of focal atrophy in vivo and demonstrating the progression of degenerative diseases.

Atrophy↗

Corpus callosum atrophy is associated with mental slowing and executive deficits in subjects with age-related white matter hyperintensities: the LADIS Study.

BACKGROUND: Previous research has indicated that corpus callosum atrophy is associated with global cognitive decline in neurodegenerative diseases, but few studies have investigated specific cognitive functions. OBJECTIVE: To investigate the role of regional corpus callosum atrophy in mental speed, attention and executive functions in subjects with age-related white matter hyperintensities (WMH). METHODS: In the Leukoaraiosis and Disability Study, 567 subjects with age-related WMH were examined with a detailed neuropsychological assessment and quantitative magnetic resonance imaging. The relationships of the total corpus callosum area and its subregions with cognitive performance were analysed using multiple linear regression, controlling for volume of WMH and other confounding factors. RESULTS: Atrophy of the total corpus callosum area was associated with poor performance in tests assessing speed of mental processing--namely, trail making A and Stroop test parts I and II. Anterior, but not posterior, corpus callosum atrophy was associated with deficits of attention and executive functions as reflected by the symbol digit modalities and digit cancellation tests, as well as by the subtraction scores in the trail making and Stroop tests. Furthermore, semantic verbal fluency was related to the total corpus callosum area and the isthmus subregion. CONCLUSIONS: Corpus callosum atrophy seems to contribute to cognitive decline independently of age, education, coexisting WMH and stroke. Anterior corpus callosum atrophy is related to the frontal-lobe-mediated executive functions and attention, whereas overall corpus callosum atrophy is associated with the slowing of processing speed.

Aged↗

Brain atrophy in frontotemporal dementia.

OBJECTIVES: To evaluate the pattern of regional brain atrophy in patients with frontotemporal dementia by comparing it with that in patients with Alzheimer's disease and normal controls. METHODS: Fourteen patients with frontotemporal dementia, 13 with moderate, and 33 with mild Alzheimer's disease, and 31 controls were studied. Atrophy was evaluated with linear measures in the anterior brain, medial temporal lobe, and hippocampal formation regions using MRI. RESULTS: Patients with frontotemporal dementia had greater atrophy in the anterior brain regions than patients with Alzheimer's disease or controls. Atrophy of the hippocampal formation, which best discriminates Alzheimer's disease from controls, was present also in patients with frontotemporal dementia. By contrast, atrophy of the medial temporal lobe, which is also present in Alzheimer's disease, was absent in frontotemporal dementia. CONCLUSION: A pattern of atrophy in the frontal lobes and hippocampal formation with sparing of the medial temporal lobe might be distinctive of frontotemporal dementia. Hippocampal involvement might not be specific for Alzheimer's disease and specific patterns of atrophy might be distinctive of some forms of degenerative dementia.

Aged↗

Urodynamic and neurophysiological evaluation in Parkinson's disease and multiple system atrophy.

AIMS: To determine whether Parkinson's disease and multiple system atrophy each has a distinct pattern of micturition abnormalities and whether a urodynamic evaluation could be useful in the differential diagnosis between the two diseases. METHODS: Sixty two patients (30 with Parkinson's disease and 32 with multiple system atrophy) underwent a complete urodynamic evaluation and neurophysiological testing. RESULTS: Of the parkinsonian patients 36.6% had normal micturition findings with normal bladder sensitivity; 26.7% had delayed or incomplete pelvic floor relaxation; 26.7% had hyperreflexia with vesicosphincteric synergy; and 10% had hyperreflexia with vesicosphincteric synergy associated with incomplete pelvic floor relaxation. Parkinsonian patients with a normal urodynamic pattern had significantly less severe disease and a shorter duration of disease in years than those who had abnormal patterns. Patients with hyperreflexia had significantly higher severity of disease. All the patients with multiple system atrophy had hyperreflexia with synergy. Two urodynamic patterns were identified: hyperreflexia with vesicosphincteric synergy (90.6% of patients), and hyperreflexia with vesicosphincteric synergy and incomplete pelvic floor relaxation (in 9.4%). Hyperreflexia with synergy correlated neither with the severity nor with the duration of disease. Sphincter EMG analysis showed that all the parkinsonian patients had normal sphincter EMG whereas 24 of the 32 patients with multiple system atrophy had neurogenic signs. CONCLUSIONS: Urodynamic evaluation and sphincter EMG are both useful tests in the differential diagnosis between Parkinson's disease and multiple system atrophy. Urodynamic findings may be abnormal before patients with multiple system atrophy reach an advanced stage of the disease. Recordings of EMGs from perineal muscles become abnormal as the disease progresses in multiple system atrophy but not in Parkinson's disease.

Aged↗

Comparison of the pattern of atrophy of the corpus callosum in frontotemporal dementia, progressive supranuclear palsy, and Alzheimer's disease.

OBJECTIVES: The loss of the neurons in layer 3, one of the groups of cortical neurons most vulnerable in various degenerative brain diseases, results in axonal degeneration leading to atrophy of the corpus callosum. Previous studies showed callosal atrophy in three degenerative dementias: frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer's disease (AD). However, it is unclear whether a characteristic pattern of atrophy is present in each. The objective of this study was to investigate whether the pattern of the callosal atrophy was different among patients with FTD, PSP, or early onset AD. METHODS: Eleven patients with FTD, nine patients with PSP, 16 patients with early onset AD, and 23 normal controls, all age and sex matched, were studied using MRI. The ratios of midsagittal corpus callosum areas to the midline internal skull surface area on T1 weighted images were analyzed. The corpus callosum was divided into quarters: the anterior, middle-anterior, middle-posterior, and posterior portions. RESULTS: Compared with controls, all three patient groups had significantly decreased total callosal/skull area ratio. An analysis of covariance adjusted for the total callosal area/skull area ratio showed that the anterior quarter callosal/skull area ratio in FTD, the middle-anterior quarter area ratio in PSP, and the posterior quarter area ratio in AD were significantly smaller than those in the other three groups. CONCLUSION: Although atrophy of the corpus callosum is not specific to any degenerative dementia, the patterns of the atrophy are different among patients with FTD, PSP, or early onset AD. Differential patterns of callosal atrophy might reflect characteristic patterns of neocortical involvement in each degenerative dementia.

Aged↗

Treatment of erectile dysfunction with sildenafil citrate (Viagra) in parkinsonism due to Parkinson's disease or multiple system atrophy with observations on orthostatic hypotension.

OBJECTIVES: To assess the efficacy and safety of sildenafil citrate (Viagra) in men with erectile dysfunction and parkinsonism due either to Parkinson's disease or multiple system atrophy. METHODS: Twenty four patients with erectile disease were recruited, 12 with Parkinson's disease and 12 with multiple system atrophy, into a randomised, double blind, placebo controlled, crossover study of sildenafil citrate. The starting dose was 50 mg active or placebo medication with the opportunity for dose adjustment depending on efficacy and tolerability. The international index of erectile function questionnaire (IIEF) was used to assess treatment efficacy and a quality of life questionnaire to assess the effect of treatment on sex life and whole life. Criteria for entry included a definite neurological diagnosis and a standing systolic blood pressure of 90-180 mm Hg and diastolic blood pressure of 50-110 mm Hg, on treatment if necessary. Blood pressure was taken at randomisation (visit 2) and crossover (visit 5) lying, sitting, and standing, before and 1 hour after taking the study medication in hospital. RESULTS: Sidenafil citrate was efficacious in men with parkinsonism with a significant improvement, as demonstrated in questionnaire responses, in ability to achieve and maintain an erection and improvement in quality of sex life. In Parkinson's disease there was minimal change in blood pressure between active and placebo medication. In multiple system atrophy, six patients were studied before recruitment was stopped because three men showed a severe drop in blood pressure 1 hour after taking the active medication. Two were already known to have orthostatic hypotension and were receiving treatment with ephedrine and midodrine but the third had asymptomatic hypotension. However, the blood pressures in all three had been within the inclusion criterion for the study protocol. Despite a significant postural fall in blood pressure after sildenafil, all patients with multiple system atrophy reported a good erectile response and were reluctant to discontinue the medication. CONCLUSIONS: Sidenafil citrate (50 mg) is efficacious in the treatment of erectile dysfunction in parkinsonism due to Parkinson's disease or multiple system atrophy; however, it may unmask or exacerbate hypotension in multiple system atrophy. As Parkinson's disease may be diagnostically difficult to distinguish from multiple system atrophy, especially in the early stages, we recommend measurement of lying and standing blood pressure before prescribing sildenafil to men with parkinsonism. Furthermore, such patients should be made aware of seeking medical advice if they develop symptoms on treatment suggestive of orthostatic hypotension.

Aged↗

Transcriptional profile of a myotube starvation model of atrophy.

Skeletal muscle wasting is a pervasive phenomenon that can result from a wide range of pathological conditions as well as from habitual muscular inactivity. The present work describes a cell-culture condition that induces significant atrophy in skeletal muscle C2C12 myotubes. The failure to replenish differentiation media in mature myotubes leads to rapid atrophy (53% in diameter), which is referred to here as starvation. Affymetrix microarrays were used to develop a transcriptional profile of control (fed) vs. atrophied (nonfed) myotubes. Myotube starvation was characterized by an upregulation of genes involved in translational inhibition, amino acid biosynthesis and transport, and cell cycle arrest/apoptosis, among others. Downregulated genes included several structural and regulatory elements of the extracellular matrix as well as several elements of Wnt/frizzled and TGF-beta signaling pathways. Interestingly, the characteristic transcriptional upregulation of the ubiquitin-proteasome system, calpains, and cathepsins known to occur in multiple in vivo models of atrophy were not seen during myotube starvation. With the exception of the downregulation of extracellular matrix genes, serine protease inhibitor genes, and the upregulation of the translation initiation factor PHAS-I, this model of atrophy in cell culture has a transcriptional profile quite distinct from any study published to date with atrophy in whole muscle. These data show that, although the gross morphology of atrophied muscle fibers may be similar in whole muscle vs. myotube culture, the processes by which this phenotype is achieved differ markedly.

Animals↗

Explicit memory in frontotemporal dementia: the role of medial temporal atrophy.

In our memory clinic experience, memory impairment differs widely in patients with frontotemporal dementia (FTD). We searched for a correlation between explicit memory disturbance assessed with the Grober and Buschke test and medial temporal atrophy on CT scan in 22 consecutive patients with FTD. Five of the 22 patients had a medial temporal lobe (MTL) atrophy. There was no significant difference between the two groups for the demographic characteristics. Free recall, cued recall and the learning curve were significantly better in patients without MTL atrophy. The patients with MTL atrophy made more intrusions. We found a positive correlation between total recall and cued recall and the mean of medial temporal lobe measurement. These results are in agreement with the role of the hippocampal formation in the memory process. In our group, the ratio of patients with MTL atrophy is similar to the ratio of Pick's disease in frontotemporal dementia. In histological series more severe hippocampal atrophy are reported in Pick's disease. Therefore MTL atrophy on CT scan could be a marker of Pick's disease in FTD.

Aged↗