Дисертації з теми "Age factors in disease"
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1
Swann, Peter G. "The visual field in age related maculopathy." Thesis, Queensland University of Technology, 1988. https://eprints.qut.edu.au/36726/1/36726_Swann_1988.pdf.
Анотація:
Age-related maculopathy (ARM) is a leading cause of permanent vision
loss in elderly people. ARM therefore constitutes an important public
health problem which will increase in magnitude as the number of aged
people in the general population becomes greater. The consequences of
this condition are exacerbated by the fact that treatment, especially
of the geographic or dry form of the disease, is ineffective. While
laser photocoagulation may be helpful in the exudative, disciform or
wet form of ARM, there is often an inexorable progression towards
severe vision loss in these patients. Therefore considerable
attention needs to be paid to the aetiology of ARM with the potential
for its prevention or delayed onset, and its recognition th rough
functional disturbances.
This study addressed the character of visual field 1 oss in ARM and
compared the efficacy of the Friedmann Visual Field Analyser, Mark II
(FVFA), the Autoplot Tangent Screen and Amsler charts in the detection
of this loss. Data for a group of subjects with ARM were compared
with those for a group of subjects with pre-age related macul opathy
(PARM), (that is, ophthalmoscopically visible changes at the macula in
the presence of normal vision (6/6)), and also with groups of elderly
and young normal subjects.
The study has shown that the visual field defects in ARM are
predominantly paracentral with a relative sparing of foveal
sensitivity. PARM subjects did not show a significant visual field
disturbance with the FVFA or Auto plot, however, three PARM subjects
did have slight distortions with the standard Amsler chart test. Of
the methods used in this study, the Amsler charts may be the preferred
method of examination of PARM subjects. Alternatively, an examination
with a static, computerised perimeter using coloured stimuli may be
used.
In the presence of visual field loss in ARM subjects, the FVFA
compared well with the Autoplot tangent screen, and highly significant
carrel ati ons were found between FVFA neutral density filter settings and equivalent Auto plot target sizes. Similarly, the Amsler charts
are a very useful method of investigation of the central visual field
and a threshold method of presentation of the test may prove helpful.
In the future, most attention should be directed towards detecting
early functional disturbances in PARM subjects. Previous research and
this study have shown that an investigation of these subjects with
high and low contrast visual acuity charts, Amsler charts, the
Desaturated D-15 test, and glare recovery tests prove more effective
than examination with the FVFA or Auto plot tangent screen. The
usefulness of examining these subjects with a computerised perimeter
using appropriate stimuli and testing strategies should be thoroughly
investigated.
2
MacIntosh, Caroline Gabrielle. "Investigation of the 'anorexia of ageing'." Title page, contents and summary only, 2000. http://web4.library.adelaide.edu.au/theses/09PH/09phm15187.pdf.
Анотація:
Includes bibliographical references (leaves 349-421) Addresses some of the mechanisms which may potentially contribute to the physiological anorexia of ageing, as suggested by previous animal and human studies.
3
STEBBINS, GLENN THURSTON III. "MEMORY FUNCTIONING IN PARKINSON'S DISEASE: THE EFFECT OF AGE OF ONSET ON HIGH SPEED MEMORY SCANNING." Diss., The University of Arizona, 1987. http://hdl.handle.net/10150/184223.
Анотація:
A sample of 25 idiopathic Parkinson's disease subjects and 25 age and education matched elderly healthy control subjects were assessed for their speed of primary memory scanning speed using the Sternberg memory scanning paradigm. In addition, all patients were assessed for cognitive functioning as measured by the Mattis Dementia Rating Scale and the Wechsler Memory Scale. Significant differences were found between Parkinson's disease subjects and control subjects on speed of primary memory scanning, with the parkinsonian subjects performing significantly slower than the control subjects. Increased variability in the measure of memory scanning speed was noted for the parkinsonian subjects as compared to control subjects and different variables associated with increased cognitive disturbances in parkinsonian subjects were investigated as possible sources of this variability. It was found that the majority of variance could be accounted for by the parkinsonian subjects' age of symptom onset. Parkinsonian subjects who developed the disease later in life were significantly slower at primary memory scanning speed than were either parkinsonian subjects who developed the disease earlier in life, or than healthy control subjects. Cognitive variables measuring initiation and perseveration, construction and attention were found to be highly associated with increased primary memory scanning time. The relationship between these cognitive abilities and frontal lobe dysfunction is discussed. Also, the possible relationship between slowing of memory scanning and dopamine depletion is presented.
4
Allen, Annette Marie. "AIDS and Aging: Are the Eldery Becoming the New At-Risk Population?" Thesis, University of North Texas, 1994. https://digital.library.unt.edu/ark:/67531/metadc278037/.
Анотація:
This dissertation breaks new ground. It examines the perceptions of older adults towards AIDS prevention. Using the National Health Interview Survey, 1988: AIDS Knowledge and Attitudes Supplement, a modified Health Belief Model is developed. Despite the low number of older adults 55+ with AIDS, some extenuating circumstances increase their risk of AIDS contraction. Older adults have lower levels of knowledge about AIDS, weaker immune systems and receive more blood transfusions. Societal influences include educational neglect at the hands of physicians, healthcare workers and social service personnel. The first stage of the dissertation involved establishing older adults as an at-risk population through an extensive literature review. Next, the data was described utilizing frequencies, correlations and factor analysis. Frequencies clearly indicated that older adults in the data set had low levels of AIDS knowledge and did not view themselves at risk for AIDS contraction. Correlations between the variables were minimal. A modified Health Belief Model was developed and tested. Multiple regression determined that minimal variation in the two dependent variables, "Perceived Effectiveness of Effective Methods to Prevent AIDS Contraction" and "Perceived Effectiveness of Ineffective Methods to Prevent AIDS Contraction" was accounted for by the independent variables. Although F ratios allowed rejection of the two null hypotheses, beta weights were low. Adjusted R^2's accounted for only 21% and 16% respectively of the variation in the dependent variables. Finally, discrepancies in the model were determined and recommendations made for further research. Most health belief models concentrate on individual social-psychological variables. Due to AIDS' societal consequences, it is proposed that societal providers of education: physicians, social service workers and healthcare personnel need to be included in the model. Recommendations were made for additional research into sexual behavior of older adults and exploration of available training of physicians, healthcare and social service professionals. Finally, recommendations were made to provide training and education for both professionals as well as the elderly to prevent their growth into an at-risk population.
5
SWANDA, REX MICHAEL. "FREE RECALL AS A FUNCTION OF AGE OF ONSET, MEDICATIONS, AND DEPRESSION IN PARKINSON'S DISEASE." Diss., The University of Arizona, 1985. http://hdl.handle.net/10150/188054.
Анотація:
Thirty-two parkinsonians were compared to 32 age-, sex-, and education-matched healthy controls on measures of depression (Beck Inventory), dementia (Mattis Dementia Rating Scale), and primary and secondary memory components of Free Verbal Recall. Parkinsonians were found to be more depressed, with greater impairment of secondary memory. There were no significant group differences in primary memory or general cognitive functioning. Sub-groups of 41 parkinsonians (including the 32 patients described above) were used to compare the relative contributions of depression, age of onset, and general cognitive decline to the observed secondary memory deficit. Depressed parkinsonians demonstrated more impaired primary memory than did nondepressed parkinsonians, but did not account for the difference in secondary memory. Parkinsonians with later ages of onset demonstrated greater depression and cognitive decline over a shorter length of illness, and parkinsonians with greater cognitive decline performed more poorly on the measure of secondary memory. Comparisons of parkinsonians with predominant unilateral motor symptoms (either right or left) to those with equal bilateral symptoms revealed the bilateral group to be significantly older, with later ages of onset but no difference in length of illness. It is concluded that later age of onset is a critical factor that is more likely to be associated with depression and declines in cognitive functioning than is seen with earlier age of onset. The relationship between age of onset and cognitive decline is not accounted for by age alone, length of illness, nor by the interaction of age with parkinsonian symptoms. Furthermore, the presence of bilateral symptoms may serve as a marker for the cluster of symptoms associated with later ages of symptoms onset.
6
Seth, Aruna. "Age-associated alterations in the immune system of normal and autoimmune-susceptible mice." Diss., This resource online, 1990. http://scholar.lib.vt.edu/theses/available/etd-07282008-135119/.
7
Cole, Leonie J. "Pain perception and processing in ageing and Alzheimer's disease /." Connect to thesis, 2009. http://repository.unimelb.edu.au/10187/4543.
8
Mui, Tammy. "Exploring biological risk factors of chronic obstructive pulmonary disease : old age and female sex." Thesis, University of British Columbia, 2009. http://hdl.handle.net/2429/24015.
Анотація:
Chronic obstructive pulmonary disease (COPD) has various risk factors including old age and female sex; however, the biological reasoning behind these is not fully understood. COPD prevalence and mortality increase with age. COPD patients also seem to demonstrate pulmonary and systemic accelerated aging. When people age, repetitive
sequences at their chromosomes ends, called telomeres, shorten. In COPD this may occur at an increased rate due to increased cell turnover or DNA damage, caused by inflammation and oxidative stress, and could contribute to lung function decline. Therefore, we measured telomere length in peripheral blood cells of COPD patients using
qPCR and examined the relationship with lung function (FEV₁ % predicted, FVC % predicted and FEV₁/FVC) as well as inflammatory marker levels. We found that telomere length was positively related to FEV₁/FVC and negatively related to serum SP-D level, a lung specific marker of inflammation. This supports that COPD is a disease of accelerated aging and suggests that lung inflammation may be involved in the process.
Females seem to be more susceptible to developing COPD than males. A major distinction between males and females is their sex hormone levels. The lung has sex hormone receptors and there are reports of experimental animal studies and observational
human studies suggesting that sex hormones have an effect on the lung. Hence, in COPD patients we measured levels of the hormones estradiol, progesterone, testosterone, luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin in their serum using ELISAs. The hormone levels of COPD patients fell within normal
ranges and had expected relationships with age and BMI. We found a significant negative association between estradiol and FVC % predicted in males; an inverse relationship between progesterone and FVC % predicted in both sexes; and a positive
relationship between LH concentration and FEV₁ % predicted in females. These data support that sex hormones affect lung function, though the mechanism by which they do so is unclear due to the scarcity of knowledge in the field. Telomeres and sex hormones seem to play a role in the risk factors of aging and female sex, respectively, and offer insight into COPD pathogenesis, though more
research is needed.
9
Jump, Seth. "Fgf2-stimulated proliferation is lower in muscle precursor cells from old rats." Diss., Columbia, Mo. : University of Missouri-Columbia, 2009. http://hdl.handle.net/10355/6775.
Анотація:
Thesis (Ph. D.)--University of Missouri-Columbia, 2009.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2009" Includes bibliographical references.
10
Vishnivetskaya, Anastasia. "Age is a risk factor for Aβ₄₂ proteotoxicity in Drosophila melanogaster". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610287.
11
Tlou, Boikhutso. "Statistical methods to model the influence of age and gender on the behavioral risk factors of HIV/AIDS." Thesis, University of Fort Hare, 2010. http://hdl.handle.net/10353/400.
Анотація:
The effects of gender and age on the behavioral risk of HIV/AIDS are not clearly understood as previous distinct studies which have been carried out, have given disputable and contradictory outcomes. This study therefore, discusses the statistical methods which can be used to model the influence of age and gender on the behavioral risk factors of HIV/AIDS. In general, generalized linear models are the main methods which can be applied to depict the impact of age and gender on the behavioral risk of becoming infected with HIV/AIDS virus. In this study, the main methods used were logistic regression, log-linear regression and multiple regressions. Behavioral risk was taken as the dependent variable while age, gender, number of sexual partners, religious beliefs and alcohol and drug abuse were fitted as predictor variables. The three statistical methods gave significant results for gender and insignificant results for age. Furthermore, comparisons were made on the three regression methods and the logistic regression gave the best results. It was therefore concluded that gender plays a significant role on the behavioral risk of HIV/AIDS. The results of the study showed that gender of the student and number of sexual partners had a significant effect on the risk behavior of the university students. In future, it may be very important to find out why age is not a significant factor on risk behavior of HIV/AIDS among university students.
12
Hoh, Kam M. J. "Age-related changes in the retina and the risk factors leading to the onset of disease." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1333225/.
Анотація:
Age-related macular degeneration (AMD) is the most prevalent form of irreversible blindness in those over 50 years old in Western countries. It is a late-onset, neurodegenerative retinal disease, which is characterised by extracellular deposits containing amyloid beta peptides (Aβ) on the Bruch’s membrane. In half of AMD cases, polymorphisms in the gene encoding complement factor H (CFH) are associated with susceptibility to the disease. The aims of this thesis were; (1) to identify sites of Aβ accumulation in mouse ageing eye and macrophage up-regulation, (2) to investigate the effects of immunotherapy targeting Aβ as a potential treatment for AMD, (3) to examine how pathogens trigger retinal disease in CFH mice, (4) to determine whether the strategy of inhibiting complement component C3 (C3) and complement activation is beneficial or detrimental in CFH mice. I show that Aβ deposition increases with age and is accumulated on photoreceptor outer segment and on Bruch’s membrane. Systemic administration of an antibody targeting Aβ improved retinal pathology, by decreasing deposits and reducing the activation of C3. I also show that genetic mutation or polymorphism is not the only factor triggering the onset of AMD but also environmental factors such as pathogen load are also critical. C3 deficiency resulted in Aβ deposition and photoreceptor cell loss along with failure to activate macrophages, supporting a beneficial, neuroprotective role of C3 in the retina. Collectively these data show that inflammation is one factor that forms an umbrella for the onset and progression of AMD. However, inflammation is not always a negative phenomenon. Aβ deposition and pathogen load are factors that will trigger an inflammatory response in tissue and therefore ways to regulate inflammatory responses to physiological levels and subsequently removing the factor causing the inflammation without affecting the homeostasis of the tissue will be a step forward in treating AMD.
13
Gibbs, John P. "Age-dependent busulfan disposition and its relation to GSTA1-1 expression /." Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/7931.
14
Lindoff, Claes. "Haemostasis during pregnancy and perimenopausal age studies of fibrinolytic components and coagulation factors involved in vascular disease /." Lund : Dept. of Obstetrics and Gynaecology, Lund University, 1994. http://catalog.hathitrust.org/api/volumes/oclc/39750405.html.
15
Profant, Judith. "Fatigue and sleep complaints in women treated for breast cancer /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2004. http://wwwlib.umi.com/cr/ucsd/fullcit?p3129934.
16
Cornett, Patricia F. Hall James. "Factors of the geriatric depression scale that may distinguish between four cognitive diagnostic groups normal, mild cognitive impairment, dementia of the Alzheimer's type, and vascular dementia /." [Denton, Tex.] : University of North Texas, 2009. http://digital.library.unt.edu/ark:/67531/metadc12105.
17
Wong, Jencia. "Age of diagnosis as a factor in the heterogeneity of type 2 diabetes: a clinical and molecular study." Thesis, The University of Sydney, 2009. https://hdl.handle.net/2123/28210.
Анотація:
The age range at which type 2 diabetes develops has recently
expanded. Thus chronological age and age of onset are now important
variables in this already heterogeneous disease. The increasing
prevalence of early-onset diabetes in particular raises clinical and
societal concerns. Such individuals have a longer life-time disease
duration and potentially can develop more diabetes related
complications, at a relatively young age, perhaps during the most
productive periods of their lives. The determinants of, and impact on
outcome of age of onset as a clinical variable are unclear. Therefore
studies using both clinical data and molecular techniques are employed
to answer questions in this area.
Whether the factors that impact on the development of type 2 diabetes
are specifically different for those with younger onset as compared to
older onset disease is not clear. By way of three studies, the first part of
this thesis explores the general question of ‘what determines the age
of type 2 diabetes onset?’
The specific impact of the metabolic syndrome, insulin resistance and
body weight on the age of type 2 diabetes onset is examined in two
different ethnic groups. This is in recognition of the paucity of specific
data in this area and the differing prevalence of the metabolic syndrome
in different ethnicities. This is examined in Chapter 2. The ‘accelerators’
of disease onset were quite different, dependent on ethnicity. Weight,
insulin resistance and a high prevalence of the metabolic syndrome are
associated with early-onset disease in Anglo-Celtics, but not so in
Chinese. The mechanistic and public health implications of these
observations are discussed.
18
Hartman, Mikael. "Risk and prognosis of breast cancer among women at high risk of the disease /." Stockholm : Karolinska institutet, 2007. http://diss.kib.ki.se/2007/978-91-7357-303-0/.
19
Bloomstrand, Mollie Anne. "An analysis of learning and memory in two aged chimpanzees." Thesis, Georgia Institute of Technology, 1985. http://hdl.handle.net/1853/28573.
20
Cayo, Quiñe Alexandra, Valeria Martínez-Vargas, and Rossi Bustamante-Voysest. "Uso incorrecto de inhaladores de dosis medida en pacientes adultos de un hospital de Callao, Perú, 2014: estudio transversal." Medwave Estudios Limitada, 2015. http://hdl.handle.net/10757/579698.
Анотація:
BACKGROUND
Inhalation therapy has proven to be the best way to control the asthma and chronic obstructive
pulmonary disease symptoms. The most commonly used delivery system to control these symptoms is
the metered-dose inhaler. The primary goal of this study is to demonstrate an association between
incorrect inhaler use and patient age.
METHODS
This is a cross-sectional study, performed at Centro Médico Naval “Cirujano Mayor Santiago Távara”, in
Callao, Peru, in 2014. Patients older than 18 years that used metered-dose inhalers were included. We
used film recordings of patients using a metered-dose inhaler and compared their technique with the
recommendations on the guidelines on the correct use of inhalers of the Spanish Society of Pneumology
and Thoracic Surgery (SEPAR). The main variables measured were age and incorrect inhaler use. The
results were analyzed with the Chi squared test for bivariate analysis, and for multivariate analysis we
used the Poisson regression model with robust variance.
RESULTS
We included 378 patients in the analysis; 167 were older than 60 years. An association was found
between incorrect inhalator technique and age (p=0.014) (PR 1.19 95% CI 1.03 to 1.37). The highest
prevalence of incorrect technique was found in the young adult population (88%). There was no
association between the incorrect technique and the person who taught it (p=0.114). Finally, this study
showed that 81.2% of the study population presented an incorrect inhalation technique.
CONCLUSIONS
The percentage of incorrect inhaler use, in the general population is high. Even if we found no association
between an incorrect technique and the person who taught it; still, there is a high percentage of errors
and it was even demonstrated that being instructed by a pulmonologist does not guarantee a correct
performance of metered-dose inhaler inhalations.INTRODUCCIÓN La terapia inhalatoria ha demostrado ser la más rápida y eficaz para el control del asma y la enfermedad pulmonar obstructiva crónica. El inhalador de dosis medida es el más usado por la población. El objetivo de este estudio es evidenciar la asociación entre la técnica inhalatoria incorrecta y la edad. MÉTODOS Estudio observacional, analítico, de corte transversal realizado en Perú durante 2014. Se incluyeron pacientes desde los 18 años que utilizaran inhalador de dosis medida. Se utilizó una lista de verificación de pasos establecidos por la Sociedad Española de Neumología y Cirugía Torácica y filmaciones para evaluar la técnica inhalatoria de los pacientes. Las variables principales fueron la edad y la mala técnica inhalatoria práctica. Para el análisis bivariado se utilizó la prueba Chi cuadrado y para el análisis multivariado regresión de Poisson con varianza robusta. RESULTADOS Se incluyeron 378 pacientes; 167 fueron mayores de 60 años. El estudio reveló que el 81,2% de la población presentó una incorrecta técnica inhalatoria. Se encontró asociación entre la edad y la técnica inhalatoria incorrecta (p=0,014) (PR 1,19 con IC 95% 1,03-1,37). El grupo etario con mayor frecuencia de técnica incorrecta fue el de adultos jóvenes (88%). CONCLUSIONES La frecuencia de uso incorrecto del inhalador en la población es alta y esta característica predomina en el grupo de adultos jóvenes. A pesar de no haber asociación entre la persona que enseña la técnica inhalatoria y el desempeño de la misma, se demostró que existe alta frecuencia de errores, incluso en aquellos pacientes instruidos por un médico especialista.
21
Schölvinck, Elisabeth Henriëtte. "The influence of age on the cellular immune response in patients with tuberculosis and healthy controls." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/53126.
Анотація:
Thesis (PhD) -- Stellenbosch University, 2002.ENGLISH ABSTRACT: Children and adults may differ in their immune function. An adequate function of the individual's immune system is crucial to the risk for development of tuberculosis (TB) after infection with Mycobacterium tuberculosis (Mtb). Epidemiological evidence suggests an age-related incidence of TB. Furthermore, the prevailing clinical expression t ' of TB varies between age groups. -The aims of this study were to characterise the cellular immune response at different ages in TB patients and healthy individuals living in a region highly endemic for TB and to relate the findings to the clinical expression of TB in different age groups. A total of 150 persons of different ages were included in this study: 50 TB patients, (identified on the basis of clinical, radiological and microbiological characteristics), 49 healthy Mantoux positive (~15mm) and 51 healthy Mantoux negative (<15mm) subjects. All patients <12yrs were identified as having primary TB and postprimary TB was only diagnosed in patients ~12yrs. Haematologic indices were obtained from all the included subjects and found to be agerelated. With the exception of the absolute lymphocyte counts, all indices were significantly different in TB patients when compared to healthy controls. Whole blood was cultured and stimulated with PHA, PPD and ESAT -6 to measure lymphocyte proliferation and IFN-y, TNF-a, IL-2 and IL-10 production in the supernatants of the cultures. After stimulation with PHA, the production of IFN-y, TNF-a and IL-10 as well as lymphocyte proliferation were all age-related. After stimulation with PPD, age correlated positively with IFN-y production in healthy Mantoux positive subjects< 12yrs. In the age groups <20 yrs, patients produced similar amounts of IFN-y when compared to healthy age-related Mantoux positive controls. TNF-a and IL-2 production were not different between patients and controls. In this whole blood system, measuring any of these cytokines on their own did not differentiate patients from controls at all ages. The ratio of PPD stimulated IFN-y to TNF-a production was significantly less in patients with primary TB and postprimary TB when compared to Mantoux positive controls, irrespective of age. These findings indicate that calculated ratios between several cytokines may be useful markers of disease at all ages. ESA T -6 stimulated IFN -y production did not result in any significant correlation with age, but was significantly less in healthy Mantoux positive subjects ~12 yrs when compared to healthy Mantoux positive subjects <12 yrs and TB patients of all ages. This finding suggests that a positive immune response to ESAT -6 is indicative of recent immunological contact with Mtb. Total IgE was measured in serum. In children <12 yrs these values correlated with age and were highest in healthy Mantoux positive controls, thereby not confirming any inverse correlation between IgE and TB. Age should be recognised as a significant variable in quantitative measurements of cellular immune responses.
AFRIKAANSE OPSOMMING: Die immuunsisteem van kinders en volwassenes kan verskillend wees. Die mate van immuniteit van 'n individu is deurslaggewend vir die risiko om tuberkulose (TB) na infeksie met die Mycobacterium tuberculosis (M tb) te ontwikkel. Epidemiologiese bevindings suggereer dat die insidensie van TB ouderdomgebonde mag wees. V erder verskil die voorkomende kliniese beeld van TB ook tussen ouderdomsgroepe. Die doelstellings van hierdie studie was om die sellulere immuunrespons op verskillende ouderdomme by TB-pasiente en gesonde individue wat in 'n streek met hoogs endemiese TB-insidensie woon te vergelyk. Die doel was ook om vas te stel hoe hierdie bevindings by die kliniese beeld van TB by verskillende ouderdomsgroepe inpas. Daar is l50 persone van verskillende ouderdomme in hierdie studie ingesluit: 50 TBpasiente (geidentifiseer op grond van kliniese, radiologiese en mikrobiologiese karakteristieke), 49 gesonde Mantoux -positiewe (:2':l5mm) en 5l gesonde Mantouxnegatiewe (
22
Eriksson-Berg, Margita. "Hemostasis in middle-aged women with coronary heart disease /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-978-1/.
23
Bradley, Declan Terrance. "Genome-wide and complement system risk factors for abdominal aortic aneurysm, age-related macular degeneration and invasive meningococcal disease." Thesis, Queen's University Belfast, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.600124.
Анотація:
Abdominal aortic aneurysm (AAA), age-related macular degeneration (AMO) and invasive meningococcal disease (IMO) are multifactorial diseases which have genetic and environmental risk factors. The complement system is an ancient part of the innate immune system that is activated in all three of these diseases. AAA is a pathological dilatation of the abdominal aorta that can rupture, often causing death. AMD is a common sight-impairing inflammatory retinal disease. IMD is due to infection with Neisseria meningilidis, which can cause potentially fatal illness in some people. The aim of this work is to better understand the effect of human genetic polymorph isms on susceptibility to these diseases. Genome-wide association study data from collaborators (for AAA) and a public data repository (for AM D) were reanalysed to find novel genetic risk factors. Replication studies were conducted for both of these investigations. Complement system candidate gene studies were conducted for AAA, AMD and IMD using primer extension and sequencing methods. Genetic risk factors for AAA were identified in the genome-wide study, one of which, rs6511720 T in low density lipoprotein receptor (LDLR) , was associated at genome-wide significance (odds ratio 0.78; 95% confidence interval 0.69-0.86; P= 1.03x10-s). Complement gene polymorphisms were not found to be important for AAA risk. A coding polymorphism in CFB, rs12614, was identified as a novel independent risk factor for AMD. The AMD genome-wide study reanalysis identified several bio logically plausible loci that did not reach significance in a small follow-up study. Investigation of complement genes in IMO revealed that MBL2 structural polymorphisms, previously reported to be of major importance, were not associated. The AMO- and IMO-associated CFH locus was characterised in detail. The results of these investigations improve understanding of the pathogenesis of all three diseases. This knowledge may play a part in facilitating the development of new preventative and therapeutic strategies.
24
Murugasen, Serini. "Age at menarche and menopause : their correlates and association with selected cardiovascular disease risk factors among 300,000 Chinese women in the China Kadoorie Biobank." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:3e5b66b9-0782-47c3-89a2-d95400e11689.
Анотація:
Background: Age-standardised mortality rates for cardiovascular disease (CVD) are generally higher among men than women, prompting suggestions that reproductive factors may be partly responsible. Moreover, there have been major changes in women’s reproductive patterns and CVD rates in China over the last few decades, but the association between them is still poorly understood. Objectives: To start addressing these issues, this thesis examines the secular trends and correlates of age at menarche and menopause (the major physiological events defining a woman’s reproductive window), as well as their association with blood pressure and anthropometry in 302,180 women born in 1930-74 from 10 areas across China using cross-sectional demographic, behavioural, physical and reproductive data from the China Kadoorie Biobank. Results: Mean age at menarche decreased by 2 years over a 44-year period (1930-1974), with the exception of an increase of about 1 year for women exposed to the Great Chinese Famine in early adolescence. No other factor showed as large an effect on age at menarche. Among women aged >57 years at the baseline, mean age at menopause increased by 1.4 years over a 21-year period (1930-1951) and was significantly associated with several reproductive and behavioural factors, notably gravidity (2 years later menopause) and smoking (6 months earlier menopause). Blood pressure and anthropometry were weakly inversely associated with age at menarche (0.2mmHg and 0.2kg/m² lower per year later menarche) and even more weakly positively associated with age at menopause (0.06mmHg and 0.04kg/m² higher per year later menopause). These trends and associations all varied to some extent by area and socioeconomic status. (All p-values <0.0001) Conclusion: This study adds new information on the secular trends and correlates of age at menarche and menopause in a large Chinese population born around the mid-20th century and provides a basis for further prospective work on the association of reproductive history with the incidence of CVD in China.
25
Anderson, Ericka Lisle Barakat Lamia. "A prospective examination of neuropsychological functioning in preschool-age children with sickle cell disease and its association with psychosocial factors /." Philadelphia, Pa. : Drexel University, 2005. http://dspace.library.drexel.edu/handle/1860/610.
26
Wong, Chun-yam Fanny, and 黃峻崟. "Is secondhand smoking related to stroke in old age in Hong Kong?" Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39724633.
27
Thomas, Aleysha. "Ensemble statistical modelling of risk factors in health." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/120675/1/Aleysha_Thomas_Thesis.pdf.
Анотація:
This thesis aims to identify and characterise the combined effects of non-genetic risk factors, particularly quantitative measurements of organochlorine pesticide (OCP) exposure, on the age at Parkinson's Disease onset using an ensemble modelling approach with linear models, decision trees, hierarchical models, meta-analyses and Bayesian networks when only disparate data sources are available, and it is expensive and time-consuming to coordinate large-scale studies. Although the results of the analysis are not conclusive due to the nature of the data sources, our results justify further study on the combined effects of quantitative non-genetic risk factors, particularly OCP exposure, in a population study.
28
So, Hon-fai, and 蘇漢暉. "Age-dependent effects of mitochondrial function in skin fibroblasts and skeletal muscle derived from a Parkinsonian LRRK2 R1441G knockinmouse model." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50162846.
Анотація:
Parkinson's disease (PD) is an age-related neurodegenerative disease characterized by the selective loss of dopaminergic neurons in the substantia nigra of the brain. The pathogenesis and etiology of PD are unclear. Mitochondrial dysfunction occurs in PD, causing a decrease in complex I activity in postmortem brain, and exacerbating reactive oxygen species production and ATP deficiency contributing to neuronal cell death. Mutation of leucine-rich-repeat kinase 2 (LRRK2) gene is the most common genetic factor identified in both familial and sporadic PD cases. Several mutations in LRRK2 have been linked to PD, in which R1441G is the second commonest mutation after G2019S. LRRK2 protein is ubiquitously expressed in human body, in which a portion is localized to the mitochondria. Mutations of LRRK2 directly or indirectly cause mitochondria dysfunction. Dysfunction of mitochondrial respiratory complexes has been described in skin fibroblasts and skeletal muscle of PD patients. Therefore, these clinically accessible tissues are good for monitoring disease progression. The objectives of this study were to investigate how LRRK2 R1441G mutation affects normal mitochondrial function, and whether this specific LRRK2 mutation potentiates age-dependent deterioration of mitochondrial function.
To achieve these aims, colonies of skin fibroblast carrying LRRK2 R1441G mutation or wild-type LRRK2 were derived from a novel LRRK2 R1441G knock-in (KI) mouse model and its wild-type (WT) littermates. Skeletal muscles were dissected from the hind legs of WT and KI mice. The effects of aging and LRRK2 R1441G mutation on mitochondrial function were investigated in vitro using these derived skin fibroblast cultures, and ex vivo using skeletal muscle obtained from young (3-month-old) and aged (18-month-old) WT and KI mice. Reduction-oxidation activities of mitochondrial complex I and complex II in skin fibroblasts and skeletal muscle were measured spectrophotometrically. Intracellular ATP levels in skin fibroblasts were determined by bioluminescent assay.
Phase-contrast microscopy showed that aging and LRRK2 R1441G mutation did not affect cell morphology of the derived skin fibroblast cultures. Complex I activity determined in skin fibroblasts and skeletal muscle derived from KI and their WT littermates revealed that, aging caused a significant increase in complex I activity in WT but not KI skin fibroblasts. Conversely, a significant decrease in complex I activity was observed in both WT and KI skeletal muscle, demonstrating an aging effect ex vivo. LRRK2 R1441G mutation did not affect complex I activity in WT and KI skin fibroblasts and skeletal muscle. Moreover, complex II activity in these two tissues was neither affected by aging nor R1441G LRRK2 mutation. Intracellular ATP levels in the skin fibroblast cultures were also unaltered by aging and LRRK2 R1441G mutation.
In conclusion, my current findings indicated a significant aging effect on mitochondrial complex I activity ex vivo, supporting the role of age-dependent deterioration of complex I activity in mitochondrial dysfunction of PD. LRRK2 R1441G mutation did not affect complex I and II activities in both skin fibroblasts and skeletal muscle. Also, this mutation did not potentiate the age-dependent deterioration of complex I activities as observed in skin fibroblasts and skeletal muscle of the LRRK2 R1441G knock-in mice.published_or_final_version
Medicine
Master
Master of Philosophy
29
Williams, M. A. "Alzheimer's disease and age-related macular-degeneration : is complement factor H a common denominator?" Thesis, Queen's University Belfast, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.546431.
30
Sofat, R. "Is complement factor H a shared risk factor for age-related macular degeneration and cardiovascular disease?" Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1331906/.
Анотація:
Background and Aims: Inflammation is implicated in common disorders of ageing including atherosclerosis and age-related macular degeneration (AMD), although the link between inflammation and cardiovascular disease (CVD) is the more studied. The recent finding that susceptibility to AMD is increased substantially by common single nucleotide polymorphisms (SNPs) in the gene that encodes complement factor H (CFH; a circulating inhibitor of complement activation) provides evidence that inflammation in general, and complement in particular, maybe causally involved in AMD. Since AMD and atherosclerosis share similar pathological features and risk factors, including a link with inflammation, an important question arises: is complement factor H (fH) a shared risk factor for both AMD and CHD? One SNP in particular, which has the most replicated association in AMD, rs1061170, which encodes a putative functional tyrosine to histidine change (Y402H), and has been studied in both AMD and coronary heart disease (CHD). I hypothesised that genetic variants in CFH, in particular rs1061170 is associated with risk of both AMD and CHD and that this association may be mediated through changes in circulating fH concentration. I addressed this hypothesis by: (i) precisely defining the effect of the association of the rs1061170 SNP encoding Y402H in CFH on AMD risk; (ii) precisely defining the association of rs1061170 on risk of CHD events; and (iii) developing and validating a high throughput assay of circulating fH, to enable further evaluation of the nature of the association between CFH genotype and fH concentration, and fH concentration and disease; (iv) measuring fH in a population based sample to determine its non-genetic correlates and genetic determinants (v) measuring fH in case control studies of AMD and genotyping of SNPs in the CFH and related genes to determine the concordance of the genetic associations of fH and AMD. Methods: To address aims (i) and (ii), I conducted a systematic review of published studies investigating the effect of variants in CFH on AMD and CHD risk respectively, supplementing data with results from newly genotyped studies in both AMD and CHD. To address aim (iii) I developed and validated a high-throughput assay measuring circulating fH, which I used to undertake studies in aim (iv) in which I measured fH in a population based sample with an existing range of blood and lifestyle measures as well as anthropometric, cardiovascular, glycaemic, lipid, liver, renal, and inflammation markers. In addition to this genome wide information was also available on ~500,000 SNPs across the genome with additional imputation of un-typed SNPs, giving coverage of ~ 2 million markers across the genome. In order to achieve aim (v) I measured fH in case control studies of AMD, with additional genotyping of SNPs in the CFH and CFH related gene in order to attain a more high resolution signal of association in this genomic region for both fH concentration and AMD risk. Results: Data synthesis from published literature and newly genotyped studies, confirmed the strong association of the rs1061170 SNP with risk of AMD (per-allele odds ratio (OR) of 2.30, 99% CI 1.93, 2.73; p<0.001), in individuals of European descent, although the association was less clear in individuals of Chinese or Japanese descent. However, there was no association of rs1061170 with CHD (per-allele OR 1.01 95% CI 0.98, 1.04), or established risk factors for CHD. Adaptation of an existing commercial, low through-put assay allowed the development and validation of a high throughput assay to measure circulating fH concentrations. With an operating range of 7-1000 mg/L, this assay was reliable, repeatable and robust, enabling assay of fH in stored samples. In a large population study, novel associations of fH with lipids, apo-lipoproteins and indices of adiposity were identified and genetic determinants localised to the CFH/CFHR gene cluster on Chromosome 1. In case-control analysis, there was no association of fH concentration with AMD risk. Conclusions: Genetic variation in CFH, and in particular the effect of the most replicated rs1061170 SNP is robustly associated with AMD with little attenuation in the effect size as data has accrued. However the effect of the same SNP is not associated with CHD. Circulating fH is associated with a range of cardio-metabolic biomarkers and regulated by common genetic variants in the vicinity of the encoding gene on chromosome 1. However fH itself is not associated with risk of AMD, suggesting the genetic association of CFH with AMD is mediated through altered fH function or perhaps through an fH-related protein encoded by an adjacent gene.
31
Alexander, Claire M. "Risk Factors for Alzheimer's Disease: Examination of the Effects of Traumatic Brain Injury and Apolipoprotein E." Ohio University / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1610371643413149.
32
Sporik, Richard Bernard. "The natural history of allergic diseases in children : a prospective clinical, immunological and environmental study." Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295805.
33
Pringle, Nadine Alex. "Characterization of a glycated gelatin model to explore the therapeutic properties of macrofungi in diabetic wound healing: an in vitro study." Thesis, Nelson Mandela Metropolitan University, 2017. http://hdl.handle.net/10948/11992.
Анотація:
Diabetic wounds frequently undergo impaired and prolonged wound healing due to a multitude of factors including hypoxia, impaired angiogenesis, hyperglycaemia, formation of ROS and AGEs, and infection - all of which may lead to cellular dysfunction. To date, however, treatment options for individuals suffering from impaired diabetic wound healing are limited, non-specific, and generally unsuccessful. The search for new and effective treatment strategies is severely hampered by the availability of adequately characterized screening models which comprehensively mimic the complexity of the diabetic wound healing process. In order to explore natural products as potential therapeutics to treat diabetic wounds and to encourage more research on this topic, this study sought out to develop and characterize a more convenient and cost effective in vitro screening assay which mimics the effects of protein glycation on the healing process of diabetic wounds. As proof of principal, this model was subsequently used to screen the potential of five wild mushroom species (P. tinctorius, R. capensis, B. badius, P. ostreatus and G. lucidum) as suitable diabetic wound healing therapies. The glycated gelatin model developed during this study was found to suitably mimic the diabetic state as it successfully simulated the major cellular dysfunctions in macrophages (NO production, phagocytosis, macrophage polarization, NF-ĸB translocation and COX-2 expression) and fibroblasts (proliferation and migration) documented during diabetic wound healing. Together these findings provide confidence that the model may serve as a valuable tool to study the poorly understood mechanisms which characterize cellular dysfunction in response to AGE accumulation and also to aid the identification of novel therapeutic agents to treat this pathology. Screening a number of mushroom extracts revealed that the ethanol extracts of R. capensis and P. ostreatus had the greatest potential for attenuating chronic inflammation due to their ability to promote macrophage phagocytosis, increased M2 activation (R. capensis) and decreased M1 activation (P. ostreatus) as well as reduced COX-2 expression while the water extract of G. lucidum proved to be the most promising candidate for stimulating fibroplasia as it was the most successful at promoting both fibroblast proliferation and migration. Different mushroom species were thus shown to promote different stages of the wound healing process providing sufficient evidence to support further studies related to the use of macrofungi as therapeutic agents in the search for more cost-effective and efficient treatment strategies for impaired diabetic wound healing.
34
Young, Seth Allen. "Selected risk factors associated with failure to receive immunizations in an age-appropriate manner /." The Ohio State University, 1985. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487262825075109.
35
Cornett, Patricia F. "Factors of the Geriatric Depression Scale that may Distinguish between Four Cognitive Diagnostic Groups: Normal, Mild Cognitive Impairment, Dementia of the Alzheimer's Type, and Vascular Dementia." Thesis, University of North Texas, 2009. https://digital.library.unt.edu/ark:/67531/metadc12105/.
Анотація:
The purpose of the current study was to explore the relationship between cognitive status and depression in a sample of geriatric patients. Participants included 282 geriatric patients ranging in age from 65 to 96 years who were classified according to diagnosis as: DAT, VaD, MCI, and Norm. All were referred for neurocognitive testing from the Geriatric Assessment Program (GAP) at the University of North Texas Health Science Center (UNTHSC) in Fort Worth, Texas. This study sought to identify factor structures for two versions of the GDS using a geriatric sample of cognitively impaired and intact patients. It then compared these factors to each other to determine whether the GDS-15 is truly a shorter version of the GDS-30. These were then compared to a previously determined factor structure. This study explored whether the four-factors of the GDS-30 are able to differentiate cognitive diagnostic groups. Further, this study sought to identify whether the severity of cognitive decline impacted GDS factor score for each of the cognitively impaired groups. Results revealed a two-factor model of the GDS - 15 and a four-factor model with the GDS - 30. The GDS-15 factors did not differ from the first two factors of the GDS-30. Comparison between the GDS-30 factor structure and that reported by Hall and Davis (in press) revealed no significant differences despite the inclusion of a normal, non-demented group in the current study. Comparisons of subscale scores revealed that DAT patients tended to score lower than the other groups on all but the cognitive impairment subscale. Severity level analyses indicated that as severity of deficits increases, awareness of deficits decreases. This study found that although the GDS-30 is a good screening tool for depression in geriatric patients, it is not particularly useful in differentiating cognitive status group. Also, the GDS-15 was not found to be a good substitute for the GDS-30.
36
Carlson, Linda E. "Steroid hormones and memory in healthy elderly men, in women estrogen-users and non-users and in patients with Alzheimer's disease." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0021/NQ44379.pdf.
37
Navér, Lars. "Perinatal HIV-1 infection : aspects on clinical presentation, viral dynamics and epidemiology /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-983-8/.
38
Kampen, Diane L. "The relationship between estrogen and memory in healthy postmenopausal women and women in the early stages of Alzheimer's disease." Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41108.
Анотація:
The effects of exogenous estrogen administration on aspects of memory and cognition in women were examined in two studies. In Study 1, women receiving estrogen replacement therapy were compared to untreated women on four measures of verbal memory. Those receiving estrogen had significantly better scores on a measure of delayed memory for propositional material. In Study 2, women in the early stages of Alzheimer's Disease (AD) were administered either estrogen or placebo on a double-blind basis for six months. Women given estrogen showed improvement on a measure of verbal memory and spatial attention compared to the placebo controls. The combined results of these studies provide evidence that estrogen enhances aspects of verbal memory in both healthy postmenopausal women and in postmenopausal women in the early stages of AD as measured by neuropsychological tests. These effects might be mediated by actions of estrogen on neuronal morphology and physiology in brain areas important for memory and cognition.
39
Clausson, Britt. "Risk factors and adverse pregnancy outcomes in small-for-gestational-age births." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2000. http://publications.uu.se/theses/91-554-4858-5/.
40
Ongore, Dismas. "Risk factors for infection and disease with the malaria parasite in children less than five years of age in Kisumu District Nyanza Province Kenya." Thesis, University of Liverpool, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385095.
41
Eriksson, Margaretha. "The Impact of Birth Weight on Cardiovascular Risk Factors, Coronary Heart Disease and Prostate Cancer : Population-based Studies of Men Born in 1913 and Followed up Until Old Age." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6005.
42
GUTHERY, STEPHEN L. "PRIMARY IMMUNOSUPPRESSION WITH TACROLIMUS AND AGE AT TRANSPLANTATION AS INDEPENDENT RISK FACTORS FOR THE DEVELOPMENT OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE IN CHILDREN UNDERGOING LIVER TRANSPLANTATION." University of Cincinnati / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1016565901.
43
Somana, Svay Sirikul Isaranurug. "Factors associated with the occurrence of acute respiratory infections in children from six months to five years of age in Tapraya hospital, Tapraya district (Sakeo province) /." Abstract, 2004. http://mulinet3.li.mahidol.ac.th/thesis/2547/cd363/4637941.pdf.
44
Chigogora, Sungano. "Behavioural and biological predictors of depression in older age : the role of Internet use, insulin-like growth factor 1, and cardiovascular disease risk factors in the English Longitudinal Study of Ageing." Thesis, University College London (University of London), 2018. http://discovery.ucl.ac.uk/10046397/.
Анотація:
BACKGROUND: Depression is a leading cause of disability and morbidity. Its determinants are not fully understood. In the present thesis I investigated the potential role of selected behavioural and biological characteristics in predicting depression in older people: Insulin-like Growth Factor 1 (IGF-1), Internet use and cardiovascular disease (CVD) risk factors. METHODS: Participants were recruited from the English Longitudinal Study of Ageing, an ongoing prospective cohort study of adults aged 50 years and over which was established in 2002. With six waves of biennial data collection up to 2012, serum IGF-1 levels were measured from 2008 at each nurse visit. Internet use was ascertained from 2002, and characterised again with greater detail in 2012. Risk factors for CVD were measured from 2004 and investigated according to the QRISK2, Framingham and SCORE algorithms. Depression symptoms were captured using the 8-item Centre for Epidemiologic Studies Depression Scale. Prospective analyses were carried out in individuals free from depressive symptoms at baseline (range dependent on analyses: 3,435 to 7,524 participants). RESULTS: A ‘U’-shaped association between IGF-1 and depression was observed, where both lower and higher levels were associated with elevated risk. For instance, relative to men in the lowest quintile of IGF-1, the age-adjusted odds ratio [OR] (95 confidence interval [CI]) for depression symptoms after 4 years of follow-up for increasing quintiles of IGF-1 were: 0.51 (0.28, 0.91), 0.50 (0.27, 0.92), 0.63 (0.35, 1.15) and 0.63 (0.35, 1.13) (P-value for quadratic association 0.002). In multivariable logistic regression analyses, compared with Internet users, non-users were 1.73 times (CI; 1.56, 1.95) more likely to develop depression after 10 years of follow-up. In particular, using the Internet for email communication was associated with a lower risk of depression. Increased risk of depression was observed in women only for all CVD risk algorithms per standard deviation change in score as follows; QRISK2 (OR 1.60: CI; 1.30, 2.00), Framingham model (OR 1.34: CI; 1.13, 1.58), SCORE chart (OR 1.40; CI; 1.11, 1.77). CONCLUSION: The present study adds to the understanding of the aetiology of depressive symptoms by suggesting a potential role for IGF-1, Internet use, and elevated CVD risk.
45
Compte, Nathalie. "Impact of clinical factors on inflammaging and Toll-like receptors responses in old age." Doctoral thesis, Universite Libre de Bruxelles, 2014. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209155.
Анотація:
Le vieillissement s’accompagne d’une altération globale des fonctions physiologiques notamment celles de l’immunité :on parle « d’immunosénescence ». Ce processus se traduit entre autre par l’installation d’un état inflammatoire chronique caractérisé par une augmentation des taux sériques de cytokines telles que l’interleukine(IL)-6 et des protéines de la phase aigüe. Cet état proinflammatoire serait incriminé dans le déclin des fonctions physiologiques, la fragilité et les syndromes gériatriques. Par ailleurs, les maladies cardiovasculaires, la dépression et l’infection chronique par le Cytomégalovirus (CMV) sont également associés à un état inflammatoire chronique. La prévalence de ces comorbidités étant importante chez les patients gériatriques, ces maladies pourraient donc contribuer à l’association observée entre marqueurs de l’inflammation et les syndromes gériatriques.Les infections représentent un problème majeur en gériatrie. Les cellules du système immunitaire inné jouent un rôle important dans les défenses contre les agents pathogènes. La reconnaissance de ceux-ci par les cellules dendritiques, les macrophages ou les monocytes fait intervenir une série de molécules telles que les récepteurs de la famille Toll (TLR). Certains travaux suggèrent que la fonction des cellules de l’immunité innée pourrait être perturbée chez les individus âgés mais ces données restent controversées.
Dans ce travail, nous souhaitons aborder les hypothèses suivantes :
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Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished
46
Barker, Glenn A. "Carbohydrate metabolism in peripheral arterial disease." Thesis, Queensland University of Technology, 2003. https://eprints.qut.edu.au/36790/1/36790_Digitised%20Thesis.pdf.
Анотація:
Peripheral arterial disease results in varying degrees of functional disability. Although principally a disease of the vascular tree, evidence demonstrates a significant contribution from metabolic alterations within ischaemically affected skeletal muscle. This thesis was concerned with better characterising the nature of these metabolic alterations, and their contribution to the functional disability in PAD patients. It also examined the efficacy of dietary carbohydrate supplementation as a therapeutic intervention in PAD.
The activity of the pyruvate dehydrogenase complex (PDH) is an important determinant of carbohydrate metabolism, experiment I examined the possibility that the active fraction of PDH (PDHa) is lower than normal in skeletal muscle of patients with intermittent claudication (IC) or patients with chronic limb ischaemia and rest pain (RP). A resting muscle biopsy was taken from the medial gastrocnemius of 11 patients with IC, seven patients with RP and eight healthy control subjects (CON). Biopsies were analysed for PDHa, acetylcarnitine, glycogen and phosphocreatine. In the RP group resting PDHa was 60 percent lower than CON (0.19 ± 0.21 versus 0.53 ± 0.27 mmol.min·1.kg·1 wet wt), but not significantly different (p = 0.09) from IC (0.42 ± 0. i 7 mmol.min·1.kg·1 wet wt); PDHa was not different between IC and CON (p = 0.54). There was no difference in muscle acetylcarnitine and glycogen between the groups, nor were there any associations between PDHa and resting acetylcamitine. Further work is warranted in determining the significance of the reduction in PDHa in the RP group, its relationship to symptoms and amenability to treatment.
Study two examined the extent to which resting metabolic changes within ischaemic muscle account for the exercise intolerance in PAD patients with intermittent claudication. Specifically, study two tested the hypothesis that walking intolerance in intermittent claudication (IC) is related to both slowed whole body V02 kinetics and depressed activity of the active fraction of pyruvate dehydrogenase (PDHa) in skeletal muscle. Ten patients displaying IC and eight healthy controls performed two familiarisation and then three maximal incremental walking tests. From these tests averaged estimates of walking time, peak V02 and the time constant of V02 ('t) during submaximal walking were obtained. A muscle sample was taken from the medial gastrocnemius muscle at rest and analysed for PDHa and several other biochemical variables. Walking time and peak V02 were -50 percent lower in IC than controls, and 't was 2-fold higher (p < 0.05). 't was significantly correlated with walking time (r = - 0.72) and peak V02 (r = -0.66) in IC; but not in controls. Resting muscle PDHa tended to be correlated with 't (r = -0.56; p = 0.09) in IC; but not in controls (r = -0.14). A similar correlation was observed between resting ABI and 't (r = -0.63, p = 0.05) in IC. This data demonstrates that impaired V02 kinetics contribute to the reduced walking capacity in IC, and that slowed V02 kinetics may result from both haemodynamic and metabolic factors in claudicants.
The final experiment examined the effects of a three-day dietary carbohydrate supplementation regime on walking capacity in claudications and in healthy control subjects. Previous work has demonstrated an ergogenic effect of CHO loading in claudicants, but failed to accurately quantify the magnitude of the improvement in walking capacity, or potential mechanisms involved in the effect. Continuing from study II, eleven PAD patients with intermittent claudication and eight control subjects performed a further two maximal treadmill tests, each preceded by a three day supplemental period. In a randomised blinded fashion, all subjects consumed a total of 700g of glucose polymer dissolved into 6 L of water (CHO), or an equal volume of artificially sweetened water (PLAC) (2Uday with meals). From baseline, walking time was significantly improved in the IC group (660 ± 331 s to 697 ± 313 s) and significantly reduced in the CON group (1335 ± 264 s to 1290 ± 250 s) following CHO. In the IC group the improvement in walking capacity was inversely associated with the initial walking capacity of the patient (r = -0.73, p < 0.05) such that for patients with an initial walking capacity of less than 400 s (n=4) there was a 23% improvement following CHO. Resting, steady state, peak V02 and the kinetics of the transitional response ('t) were unaffected by CHO, however there was an association between the change in walking time and change in 't in the IC group only (r = -0.70, p < 0.05). Resting, steady-state and maximal RER was significantly elevated following CHO in both groups. In the CON group the reduction in walking time was strongly associated with increases in body weight (r = 0.87, p < 0.05). There was no association between the change in walking performance and any muscle measure in the CON group, but in IC the improvement in walking time was inversely associated with resting PDHa (r = -0.65, p < 0.05). This data demonstrates the benefits of CHO supplementation are mainly confined to those patients with greater functional impairments and may be mediated via improvements in V02 uptake kinetics resulting from metabolic alterations within the exercising musculature.
47
Yu, Elizabeth A. "Investigating Age-Dependent Arthropathy in a Circadian Mutant Mouse Model: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/544.
Анотація:
Ectopic calcification can cause pain and limit mobility. Studies suggest that circadian genes may play a role in the calcification process. Core circadian genes Clock, Npas2, and Bmal1 are transcription factors that form CLOCK:BMAL1 or NPAS2:BMAL1 transactivator complexes that drive the rhythmic expression of circadian oscillator genes and output genes. Circadian oscillator genes Period1-3 and Cryptochrome1-2 encode proteins that form transcription repressor complexes that feedback to inhibit CLOCK/NPAS2:BMAL1 activity, thus completing the feedback loop that is the basis of the molecular circadian clockwork. Arrhythmic Bmal1-/- mice exhibit site-specific, age-dependent arthropathy. While studying the circadian phenotype of Clock-/-;Npas2m/m double mutant mice, we discovered that these double mutant mice develop site-specific arthropathy similar to the arthropathy described in Bmal1-/- mice. Based on the circadian clockwork mechanism, we hypothesized that CLOCK/NPAS2:BMAL1 transactivator complexes drive the expression of a gene (or genes) that prevents age-dependent arthropathy. To investigate Clock-/-;Npas2m/m double mutant mouse arthropathy, we evaluated mutant mice using X-ray, micro-computed tomography, and histology, and found that Clock-/-;Npas2m/m double mutant mice exhibit age-dependent, site-specific arthropathy that phenocopies that of Bmal1-/- mice. The costosternal junction and calcaneal tendon are most prominently affected, in that calcification of those tissues is detectable as early as 4-5 weeks and 11-12 weeks, respectively. The arthropathic lesions in these tissues consist of calcium phosphate vii deposits, and in Bmal1-/- costosternal junction calcifications, the deposits contain calcium pyrophosphate dihydrate crystals. Mechanical stress, disregulation of centrally-regulated circadian rhythms, and systemic serum mineral imbalances likely do not contribute to this pathology. In vitro micromass cultures generated from Clock-/-;Npas2m/m double mutant mouse embryonic fibroblasts do not exhibit irregular chondrocyte differentiation compared to wild-type cultures, suggesting that chondrocyte cell-autonomous mechanisms are insufficient to induce this arthropathy. Analysis of Clock-/-;Npas2m/m double mutant intersternebral tissue RNA did not reveal significant changes in chondrocyte or calcification-related gene expression. Histological stains showed an absence of osteoblasts and osteoclasts around costosternal junction calcifications, suggesting that these cell types are not contributing to this pathology. Instead, chondrocytes are localized to the costosternal junction but there were no significant changes in the distribution of chondrocyte markers in this tissue, as evaluated by immunohistochemistry. These findings suggest that Clock or Npas2, and Bmal1, regulate ectopic calcification through a combination of systemic and local factors, and that the cells affected by Clock and Npas2, or Bmal1, disruption are a subset of the cells distributed in specific tissues that develop age-dependent arthropathy. The significance of these findings is that “circadian genes” play a role in the regulation of ectopic calcification in a non-oscillator capacity. Understanding this new mechanism by which ectopic calcification is controlled could lead to novel approaches for the treatment of some human calcification diseases.
48
O'Donovan, James Gary. "Exercise, cardiorespiratory fitness and coronary heart disease risk factors in men aged 30-45 years." Thesis, University of Kent, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413274.
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Ross, Amy Psychiatry Faculty of Medicine UNSW. "Longitudinal study of cognitive and functional brain changes in ageing and cerebrovascular disease, using proton magnetic resonance spectroscopy." Awarded by:University of New South Wales. School of Psychiatry, 2005. http://handle.unsw.edu.au/1959.4/27329.
Анотація:
The neurophysiological basis of cognition changes with age is relatively unexplained, with most studies reporting weak relationships between cognition and measures of brain function, such as event related potentials, brain size and cerebral blood flow. Proton magnetic resonance spectroscopy (1H-MRS) is an in vivo method used to detect metabolites within the brain that are relevant to certain brain processes. Recent studies have shown that these metabolites, in particular N-acetyl aspartate (NAA), which is associated with neuronal viability, correlate with performance on neuropsychological tests or other measures of cognitive function in patients with a variety of cognitive disorders associated with ageing and in normal ageing subjects. We have studied the relationship between metabolites and cognitive function in elderly patients 3 months and 3 years after a stroke or transient ischemic attack (TIA) and in an ageing comparison group. Metabolites were no different between stroke/TIA patients and elderly controls, however, there were significant metabolite differences between stroke/TIA patients with cognitive impairment (Vascular Cognitive Impairment and Vascular Dementia) and those without. Frontal measures of NAA and NAA/Cr predicted cognitive decline over 12 months and 3 years in stroke/TIA patients and elderly controls, and these measures were superior predictors than structural MRI measures. Longitudinal stability of metabolites in ageing over 3 years was associated with stability of cognitive function. The results indicate that 1H-MRS is a useful tool in differentiating stroke/TIA patients with and without cognitive impairment, with possibly superior predictive ability than structural MRI for assessing future cognitive decline. The changes in 1H-MRS that occur with ageing and cognitive decline have implications for the neurophysiological mechanisms and processes that are occurring in the brain, as well as application to clinical diagnosis, the early detection of pathology and the examination of longitudinal change.
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Mabasa, Matimba Allan. "The study of socio-cultural values and practices that influence the escalation of HIV and AIDS amongst the youth: a social work perspective." Thesis, University of Limpopo (Turfloop Campus), 2012. http://hdl.handle.net/10386/833.