Middle Stages Of Disease Research Articles

Falls, fractures and bone density in Parkinson's disease – a cross-sectional study

Aim: Evidence suggests that falls and associated bone fractures are more frequent in patients suffering from Parkinson's disease (PD) than in the general population. In this cross-sectional study we evaluated the clinical and biochemical characteristics that are associated to falls, fractures and bone health in a population of PD subjects. Materials and methods: Forty-two consecutive subjects suffering from idiopathic PD (mild-to-moderate severity) with/without falls in the previous year were included. They were characterized as regards functional independence, balance, fear of falling, bone density (ultrasound densitometry) and plasma levels of vitamin D. Twenty-one age- and sex-matched healthy subjects were evaluated as controls. Results: We detected a greater degree of osteoporosis in PD subjects as compared to controls, more pronounced in males than in females (Z-score: M −3.8 ± 1.6, F −2.28 ± 0.92, p = 0.0006). A positive correlation was found between independence levels and bone density or vitamin D levels. Twenty seven patients (64%) reported falls in the previous year. These were associated to post-traumatic fractures in 16 subjects (59% of fallers). Women fell more than men (fallers: 20 F/7 M; non fallers: 4 F/11 M, χ² test p = 0.02), although the occurrence of post-traumatic fractures among fallers did not differ between sexes (F 11/9, M 5/2, χ² test p > 0.05). Fallers with post-traumatic fractures showed higher degrees of motor impairment. Conclusions: These findings confirm that falls and osteoporosis represent major health issues in PD, already in the middle stages of disease.

Comparative morphometric analysis of microglia in the spinal cord of SOD1(G93A) transgenic mouse model of amyotrophic lateral sclerosis.

It has long been recognized that reactive microglia undergo a series of phenotypic changes accompanying morphological transformation. However, the morphological classification of microglia has not yet been achieved. To address this issue, here we morphometrically analysed three-dimensionally reconstructed ionized calcium binding adaptor molecule 1-immunoreactive (Iba1(+) ) microglia in the ventral horn of the lumbar spinal cord of SOD1(G93A) transgenic mice, a model of amyotrophic lateral sclerosis. The hierarchical cluster analysis revealed that microglia were objectively divided into four groups: type S (named after surveillant microglia) and types R1, R2 and R3 (named after reactive microglia). For the purpose of comparative morphometry, we also analysed two pharmacological disease models using wild-type mice: 3,3'-iminodipropionitrile (IDPN)-induced axonopathy and lipopolysaccharide (LPS)-induced neuroinflammation. Type S microglia showed a typical ramified morphology of surveillant microglia, and were mostly observed in wild-type controls. Type R1 microglia were seen at the early stage of disease in SOD1(G93A) mice, and also frequently occurred in IDPN-treated mice. They exhibited small cell bodies with shorter and simple processes. Type R2 microglia were morphologically similar to type R1 microglia, but only transiently occurred in the middle stage of disease in SOD1(G93A) mice and in IDPN-treated mice. Type R3 microglia exhibited a bushy shape, and were observed in the end stage of disease in SOD1(G93A) mice and in LPS-treated mice. These findings indicate that microglia of SOD1(G93A) mice can be classified into four types, and also suggest that the phenotypic changes may be induced by the events related to axonopathy and neuroinflammation.

I03 Swallowing Function In The Early, Middle And Late Stages Of Huntington's Disease

<h3>Background</h3> Swallowing problems are common among people with Huntington’s disease (HD). Evidence suggests that death usually results from respiratory complications often caused by dysphagia. However, there are no studies which examine systematically the swallowing function through the successive stages of HD. <h3>Aims</h3> The purpose of this study is therefore to investigate the swallowing function and provide appropriate management of oral feeding difficulties in relation to disease progression. <h3>Methods</h3> Thirty-eight patients (mean age= 50.62, SD ± 12.7) with genetically confirmed HD underwent swallowing evaluation. Each subject was clinically assessed with the Unified Huntington’s Disease Rating Scale (UHDRS) and was classified in one of the three stages of the disease (early, middle and late) according to the guidelines recommendations. <h3>Results</h3> In the early stage of HD, swallowing alterations were observed in 11% of the patients and required the application of diet restrictions, compensatory strategies and postures. The prevalence of swallowing impairments at the middle stage of the disease had the same trend as the first stage. Severe dysphagia was mainly represented in the late stage (26%); in fact, the two subjects receiving nutrition through non-oral feeding were in this stage of HD. <h3>Conclusions</h3> Although, dysphagia is challenging in the last stage of the neurodegenerative disease, swallowing difficulties occur since the disease onset. The results confirm the importance of ongoing assessment and management of dysphagia in the early stage, as recommended by the EHDN Standards of Care Speech and Language Therapy Working Group, and provide directions to further improve the quality of care delivered to HD patients.

Effective analysis on the treatment of osteonecrosis of femoral head （ONFH） by stages with self designed Chinese medicine formula

Objective To explore the clinical effects of treating osteonecrosis of femoral head（ONFH） by stages with self designed Chinese medicine formula. Methods 106 ONFH patients in Shantou municipal TCM hospital from July 2010 to July 2013 were recruited and divided randomly into a control group and a treatment group, 53 patients in each. The treatment group was treated with self-designed Chinese medicine formula with the functions of strengthening spleen and promoting blood circulation in the early stage, and self-designed Chinese medicine formula with the functions of supplementing kidney and promoting blood circulation in the middle stage of disease, one dosage daily. The control group was treated with Xianliang Gubao capsule （3 granules per time, twice daily） and lovastatin capsule （10-20 mg per time）. Both groups were treated for two therapeutic courses of 8-12 weeks. X-ray and hemorheology indexes were observed after the treatment. Results The total effects was 90.6%（48/53） and 73.6%（39/53） in the treatment group and the control group respectively, with significant difference（χ^2=6.731,P<0.05）;Whole blood viscosity, PV, HCT, Arbe, ESR, FIB were obviously improved in the treatment group after the treatment, [after the treatment： whole blood viscosity high cut（3.42±0.72）mPa·S, middle cut（4.21±0.30）mPa·S, low cut（8.36±0.12）mPa·S, PV（1.39±0.16）mPa·S, HCT（38.34±2.37）%, Arbe（5.47±0.33）, ESR（27.35±2.16）mm/h, FIB（3.83±0.47）g/L], [before the treatment：whole blood viscosity high cut（3.97±0.21）mPa·S, middle cut （4.71±0.24）mPa·S, low cut （9.58±0.31）mPa·S, PV（2.01±0.13）mPa·S, HCT（41.29±1.01）%, Arbe（6.51±0.21）,ESR（14.62±0.92）mm/h, FIB（4.94±0.26）g/L, P<0.05]. After the treatment, the treatment group was obviously improved in such indexes as whole blood viscosity high cut（3.76±0.08）mPa·S, middle cut（4.47±0.16）mPa·S, low cut （8.99±0.07）mPa·S, PV（1.72±0.14）mPa·S, HCT（40.46±1.06）%, Arbe（6.11±0.38）, ESR（24.98±1.42）mm/h and FIB（4.33±0.57）g/L than the control group（P〈0.01 or 0.05）. Conclusion Self-designed Chinese medicine formula stage-therapy had better results in treating ONFH than Xianling Gubao capsule and lovastatin. Key words: Osteonecrosis of femoral head; Treatment by stage; Therapeutic evaluation

Atherosclerosis in LDLR-Knockout Mice Is Inhibited, but Not Reversed, by the PPARγ Ligand Pioglitazone

Thiazolidinediones, a class of drugs for the treatment of type-2 diabetes, are synthetic ligands for peroxisome proliferator-activated receptor-gamma. They have been demonstrated to possess cardioprotective effects in humans and anti-atherogenic properties in animal models. However, the question remains whether a peroxisome proliferator-activated receptor-gamma ligand can reverse the development of atherosclerosis. In this study, we tested the effects of pioglitazone on the development of established atherosclerosis in low-density lipoprotein receptor-null mice. We observed that atherosclerosis in low-density lipoprotein receptor-null mice progressed when mice were fed a high-fat diet. Pioglitazone treatment of atherogenic mice prevented this progression of atherosclerosis from its middle stages of disease, but was not able to reverse it. Withdrawal of the high-fat diet from mice with advanced atherosclerosis did not result in a reduction in lesion sizes. Pioglitazone treatment also had no effect on advanced atherosclerosis. Levels of high density lipoprotein cholesterol correlated inversely with lesion development when pioglitazone was given during lesion progression. However, pioglitazone had no effect on circulating high density lipoprotein levels in mice in which treatment was initiated following 14 weeks on the high-fat diet. These findings have implications for the analysis of therapeutic agents in murine models of atherosclerosis and the use of pioglitazone in patients with established atherosclerosis.

Multidimensional exercise for people with Parkinson's disease: A case report

The primary impairments associated with Parkinson's disease occur in combination with the secondary, preventable effects of immobility. A community-based fitness program may help increase activity and maintain function in people in the early or middle stages of the disease. This article describes a unique program designed to reduce fall risk and promote independent exercise for people with Parkinson's disease. Two 66-year-old males, both community ambulators and in early or middle stages of Parkinson's disease, participated in 3 months of various physical activities. Group balance classes were held twice weekly during the first month, participants joined a fitness center and self-directed their exercise program during the second month, and group Tai Chi classes were held twice weekly during the third month. At conclusion of the program, participants were given suggestions for continued physical fitness activities. After the 3-month program, improvements were noted for both individuals in functional reach, Timed Up and Go, and Berg Balance scores. Both participants continued to exercise regularly for at least 8 months following the program. Two individuals with Parkinson's disease demonstrated improvement in their balance test performance over a 3-month period. Perhaps most importantly, these participants independently continued exercising after completing this program.

Severe hepatitis treated with an artificial liver support system

We designed an artificial liver support system (ALSS) including plasma exchange, charcoal hemoperfusion, plasma bilirubin absorption, charcoal plasma perfusion, hemofiltration and hemodialysis. We chose different methods or their combinations according to the patient's conditions. We investigated the effect of ALSS in 154 patients with severe hepatitis, 72 of whom survived. All data were analyzed by SPSS. The effectiveness of ALSS treatment was compared at different stages (i.e. early, middle and end stages). After each ALSS treatment, the liver function of these patients greatly improved, serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while BCAA/AAA ratio increased. Patients treated with ALSS in the early or middle stages of disease had much higher survival rates than patients in the end stage of disease. Thus, we concluded that ALSS is a reliable therapy for advanced liver diseases and treatment in early or middle stages is appropriate.

Acetylcholinesterase inhibitors in Alzheimer's disease.

Alzheimer’s Disease (AD) is the most common single cause of dementia in our ageing society. Traditionally thought of as an untreatable degenerative condition, recent advances in drug therapy have challenged this view. The disease is characterised by an insidious decline in cognitive and non-cognitive function. Classically, short and long-term memory is impaired while language skills, concentration and attention are often affected. This results in impaired ability to learn and retain new skills as well as the loss of existing ones. Non-cognitive function is the global term used to describe problems such as depression, agitation, personality changes, delusions and hallucinations. These factors have a significant impact on patient behaviour and a very real impact on the quality of life for both patients and caregivers. Diagnosis of AD is clinically based, and using the NINCDS-ADRDA criteria (Table 1) [1], a diagnosis of probable or possible AD can be made. Definitive diagnosis relies on pathological confirmation, which in the majority of cases is rarely completed. With the development of AD specific treatments, definition of AD from other types of dementia is very important. Table 1 NINCDS-ADRDA Criteria for clinical diagnosis of Alzheimer’s disease. Pathogenesis The pathogenesis of AD has not yet been elucidated. It is widely accepted that a combination of genetic susceptibility factors and environmental triggers are responsible for late onset sporadic AD, the most common form of the disease. An understanding of the disease mechanism remains elusive, and is the key to developing a disease modifying agent. Currently, it is proposed that beta amyloid protein, abnormal tau protein or possibly both play key factors in the development of disease. It has been widely postulated that oxidative damage and a slow inflammatory process are two possible mechanisms involved. As yet, no product with proven disease modifying properties is available, and current treatments offer symptomatic benefit only. The development of acetylcholinesterase (AChe) inhibitor drugs has followed the finding that cholinergic pathways in the cerebral cortex and basal forebrain are compromised in AD [2] and the resultant cholinergic deficit contributes to the cognitive impairment of these patients [3]. Although many believe this ‘cholinergic hypothesis’ to be important, others feel it represents a less significant component of the disease process [4]. Many other neurotransmitters are affected in AD, and the relative importance of each in relation to clinical findings has not been fully elucidated. Initial work focused on the use of acetylcholine precursors, using a similar rationale to dopamine therapy in Parkinson’s disease. A series of small trials using precursors such as choline and phosphatidylcholine showed no reliable improvement in cognitive function, with only 10 out of 43 trials reporting any positive effect [5]. There has been renewed interest in muscarinic agonists drugs, which when first introduced, had major problems with adverse cholinergic effects. Better understanding of the molecular pathology of muscarinic receptors and their subtypes has led to the development of more specific agonists. Drugs such as xanomeline, milameline, and civimeline have reached clinical trials, and the improvements seen in cognitive function are reviewed by Avery et al. [6]. There are also claims that these drugs have disease modifying properties, with effects on APP processing and tau phosphorylation. Muscarinic agonists remain in trial, but have yet to fulfil their potential in AD treatment. The only group of drugs currently licensed for AD treatment is the AChe inhibitors, which act through inhibition of the enzyme acetylcholinesterase (AChe), responsible for the breakdown of ACh in the neural synapse. A meta-analysis of the early AChe inhibitor treatments was encouraging [7] and these proceeded to larger placebo controlled double-blind trials.