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1.
J Gambl Stud ; 36(2): 477-498, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31620927

RESUMO

Compared to the general population, military personnel are particularly vulnerable to developing gambling problems. The present study examined the presentation of gambling-including gambling frequency, personal thoughts on reducing gambling and recommendations from others to reduce gambling-across these populations. Additionally, the study measured the association between gambling and various psychosocial risk and protective factors-including psychological distress, suicidal ideation, external encouragement to reduce substance use, days out of role, personal wellbeing, resilience, social support and intimate bonds. Data was extracted from the Global Health & Wellbeing Survey, an online self-report survey conducted in Australia, Canada, New Zealand, the United Kingdom and the United States. Of the 10,765 eligible respondents, 394 were military veterans and 337 were active military personnel. Consistent with previous research, a higher proportion of gambling behaviours were observed in both current and ex-serving military samples, compared to the general population. To varying degrees, significant associations were found between the different gambling items and all psychosocial risk and protective factors in the general population sample. However, the military sample yielded only one significant association between gambling frequency and the protective factor 'resilience'. A post hoc stepwise linear regression analysis demonstrated the possible mediating role resilience plays between gambling frequency and other psychosocial risk (psychological distress, and suicidal thoughts and behaviour) and protective factors (personal wellbeing) for the military sample. Given the findings, it is recommended that routine screening tools identifying problem gambling are used within the military, and subsequent resilience focused interventions are offered to at risk personnel.


Assuntos
Jogo de Azar/psicologia , Militares/psicologia , Resiliência Psicológica , Apoio Social , Veteranos/psicologia , Adulto , Austrália , Canadá , Feminino , Jogo de Azar/epidemiologia , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Militares/estatística & dados numéricos , Nova Zelândia , Fatores de Proteção , Autorrelato , Transtornos Relacionados ao Uso de Substâncias/psicologia , Ideação Suicida , Inquéritos e Questionários , Reino Unido , Estados Unidos , Veteranos/estatística & dados numéricos
2.
Brain Imaging Behav ; 10(3): 660-8, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26239997

RESUMO

The objective of this study was to investigate the relationship between cardiorespiratory (CR) fitness and the brain's white matter tract integrity using diffusion tensor imaging (DTI) in the Alzheimer's disease (AD) population. We recruited older adults in the early stages of AD (n = 37; CDR = 0.5 and 1) and collected cross-sectional fitness and diffusion imaging data. We examined the association between CR fitness (peak oxygen consumption [VO2peak]) and fractional anisotropy (FA) in AD-related white matter tracts using two processing methodologies: a tract-of-interest approach and tract-based spatial statistic (TBSS). Subsequent diffusivity metrics (radial diffusivity [RD], mean diffusivity [MD], and axial diffusivity [A × D]) were also correlated with VO2peak. The tract-of-interest approach showed that higher VO2peak was associated with preserved white matter integrity as measured by increased FA in the right inferior fronto-occipital fasciculus (p = 0.035, r = 0.36). We did not find a significant correlation using TBSS, though there was a trend for a positive association between white matter integrity and higher VO2peak measures (p < 0.01 uncorrected). Our findings indicate that higher CR fitness levels in early AD participants may be related to preserved white matter integrity. However to draw stronger conclusions, further study on the relationship between fitness and white matter deterioration in AD is necessary.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/fisiopatologia , Aptidão Cardiorrespiratória , Substância Branca/diagnóstico por imagem , Idoso , Estudos Transversais , Imagem de Tensor de Difusão , Teste de Esforço , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Comportamento Sedentário
3.
Am J Transplant ; 15(10): 2704-11, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25968609

RESUMO

Hepatocellular carcinoma (HCC) recurrence in patients undergoing liver transplantation (LT) with donation after brain death (DBD) and donation after cardiac death (DCD) allografts has not previously been investigated. Rates and patterns of HCC recurrences were investigated in patients undergoing DBD (N = 1633) and DCD (N = 243) LT between 2003 and 2012. LT for HCC was identified in 397 patients (340 DBD and 57 DCD). No difference in tumor number (p = 0.26), tumor volume (p = 0.34) and serum alphafetoprotein (AFP) (p = 0.47) was seen between the groups. HCC recurrence was identified in 41 (12.1%) patients in the DBD group and 7 (12.3%) patients in the DCD group. There was no difference in recurrence-free survival (p = 0.29) or cumulative incidence of HCC recurrence (p = 0.91) between the groups. Liver allograft was the first site of recurrence in 22 (65%) patients in the DBD group and two (37%) patients in the DCD group (p = 0.39). LT for HCC with DBD and DCD allografts demonstrate no difference in the rate of HCC recurrence. Previously published differences in survival demonstrated between recipients with HCC receiving DBD and DCD allografts despite statistical adjustment can likely be explained by practice patterns not captured by variables contained in the SRTR database.


Assuntos
Carcinoma Hepatocelular/cirurgia , Morte , Seleção do Doador , Neoplasias Hepáticas/cirurgia , Transplante de Fígado/métodos , Recidiva Local de Neoplasia/etiologia , Doadores de Tecidos , Adulto , Idoso , Aloenxertos/transplante , Morte Encefálica , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Homólogo/métodos , Resultado do Tratamento
4.
Physiol Biochem Zool ; 88(2): 167-82, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25730272

RESUMO

In adult marine mammals, muscles can sustain aerobic metabolism during dives in part because they contain large oxygen (O2) stores and metabolic rates are low. However, young pups have significantly lower tissue O2 stores and much higher mass-specific metabolic rates. To investigate how these differences may influence muscle function during dives, we measured the activities of enzymes involved in aerobic and anaerobic metabolic pathways (citrate synthase [CS], ß-hydroxyacyl-coenzyme A dehydrogenase [HOAD], lactate dehydrogenase [LDH]) and the LDH isoform profile in six muscles from 41 harp (Pagophilus groenlandicus) and 30 hooded (Cystophora cristata) seals ranging in age from fetal to adult. All neonatal muscles had significantly higher absolute but lower metabolically scaled CS and HOAD activities than adults (∼ 70% and ∼ 85% lower, respectively). Developmental increases in LDH activity lagged that of aerobic enzymes and were not accompanied by changes in isozyme profile, suggesting that changes in enzyme concentration rather than structure determine activity levels. Biochemical maturation proceeded faster in the major locomotory muscles. In combination, findings suggest that pup muscles are unable to support strenuous aerobic exercise or rely heavily on anaerobic metabolism during early diving activities and that pups' high mass-specific metabolic rates may play a key role in limiting the ability of their muscles to support underwater foraging.


Assuntos
Mergulho/fisiologia , Músculo Esquelético/metabolismo , Oxigênio/metabolismo , Focas Verdadeiras/metabolismo , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Envelhecimento/fisiologia , Animais , Animais Recém-Nascidos , Citrato (si)-Sintase/metabolismo , Feminino , Feto/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Desenvolvimento Muscular , Músculo Esquelético/enzimologia , Músculo Esquelético/crescimento & desenvolvimento , Focas Verdadeiras/crescimento & desenvolvimento
5.
Neuroscience ; 270: 139-47, 2014 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-24735819

RESUMO

The goal of this study was to compare insulin resistance in aging and aging-related neurodegenerative diseases, and to determine the relationship between insulin resistance and gray matter volume (GMV) in each cohort using an unbiased, voxel-based approach. Insulin resistance was estimated in apparently healthy elderly control (HC, n=21) and neurodegenerative disease (Alzheimer's disease (AD), n=20; Parkinson's disease (PD), n=22) groups using Homeostasis Model Assessment of Insulin Resistance 2 (HOMA2) and intravenous glucose tolerance test (IVGTT). HOMA2 and GMV were assessed within groups through General Linear Model multiple regression. We found that HOMA2 was increased in both AD and PD compared to the HC group (HC vs. AD, p=0.002, HC vs. PD, p=0.003), although only AD subjects exhibited increased fasting glucose (p=0.005). Furthermore, our voxel-based morphometry analysis revealed that HOMA2 was related to GMV in all cohorts in a region-specific manner (p<0.001, uncorrected). Significant relationships were observed in the medial prefrontal cortex (HC), medial temporal regions (AD), and parietal regions (PD). Finally, the directionality of the relationship between HOMA2 and GMV was disease-specific. Both HC and AD subjects exhibited negative relationships between HOMA2 and brain volume (increased HOMA2 associated with decreased brain volume), while a positive relationship was observed in PD. This cross-sectional study suggests that insulin resistance is increased in neurodegenerative disease, and that individuals with AD appear to have more severe metabolic dysfunction than individuals with PD or PD dementia.


Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Substância Cinzenta/patologia , Resistência à Insulina/fisiologia , Doença de Parkinson/patologia , Doença de Parkinson/fisiopatologia , Idoso , Doença de Alzheimer/tratamento farmacológico , Encéfalo/patologia , Estudos Transversais , Jejum/fisiologia , Feminino , Teste de Tolerância a Glucose , Humanos , Modelos Lineares , Imageamento por Ressonância Magnética , Masculino , Atividade Motora/fisiologia , Testes Neuropsicológicos , Tamanho do Órgão , Doença de Parkinson/tratamento farmacológico
6.
Neurology ; 77(21): 1913-20, 2011 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-22105948

RESUMO

OBJECTIVE: Both low and high body mass index (BMI) has been associated with cognitive impairment and dementia risk, including Alzheimer disease (AD). We examined the relationship of BMI with potential underlying biological substrates for cognitive impairment. METHODS: We analyzed cross-sectional data from participants enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with PET imaging using Pittsburgh Compound B (PiB, n = 101) or CSF analyses (n = 405) for ß-amyloid peptide (Aß) and total tau. We assessed the relationship of CSF biomarkers and global PiB uptake with BMI using linear regression controlling for age and sex. We also assessed BMI differences between those who were and were not considered biomarker positive. Finally, we assessed BMI change over 2 years in relationship to AD biomarkers. RESULTS: No dementia, mild cognitive impairment (MCI), and AD groups were not different in age, education, or BMI. In the overall sample, CSF Aß (ß = 0.181, p < 0.001), tau (ß = -0.179, p < 0.001), tau/Aß ratio (ß = -0.180, p < 0.001), and global PiB uptake (ß = -0.272, p = 0.005) were associated with BMI, with markers of increased AD burden associated with lower BMI. Fewer overweight individuals had biomarker levels indicative of pathophysiology (p < 0.01). These relationships were strongest in the MCI and no dementia groups. CONCLUSIONS: The presence and burden of in vivo biomarkers of cerebral amyloid and tau are associated with lower BMI in cognitively normal and MCI individuals. This supports previous findings of systemic change in the earliest phases of the disease. Further, MCI in those who are overweight may be more likely to result from heterogeneous pathophysiology.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Índice de Massa Corporal , Proteínas tau/líquido cefalorraquidiano , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Compostos de Anilina , Disfunção Cognitiva/líquido cefalorraquidiano , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Sobrepeso/complicações , Tomografia por Emissão de Pósitrons , Tiazóis
7.
Parasite Immunol ; 33(9): 512-6, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21585397

RESUMO

A genetic dissection approach was employed to determine whether the IL-2 receptor complex (IL-2R) comprised of α, ß and γ chains is required for the suppression of Plasmodium chabaudi adami parasitemia. Blood-stage infections in IL-2Rγ(c)(-/y) mice failed to cure with parasitemia remaining elevated for > 50 days indicating the IL-2Rγ(c) through which all members of the γ(c) family of cytokines signal has an essential role in protective immunity against blood-stage malarial parasites. In contrast, the curing of parasitemia in IL-2/15Rß⁻/⁻ mice, deficient in both IL-2 and IL-15 signalling was significantly delayed but did occur, indicating that neither cytokine plays an essential role in parasite clearance. Moreover, the observation that the time course of parasitemia in IL-15⁻/⁻ mice was nearly identical to that seen in controls suggests that the parasitemia-suppressing role of stimulating through the IL-2/15Rß chain is owing to IL-2 signalling and not a redundant function of IL-15.


Assuntos
Imunidade Celular , Malária/parasitologia , Plasmodium chabaudi/imunologia , Receptores de Interleucina-2/imunologia , Transdução de Sinais , Animais , Anticorpos Antiprotozoários/sangue , Eritrócitos/parasitologia , Feminino , Genótipo , Endogamia , Subunidade gama Comum de Receptores de Interleucina/genética , Subunidade gama Comum de Receptores de Interleucina/imunologia , Interleucinas/imunologia , Malária/sangue , Malária/genética , Malária/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Parasitemia/imunologia , Parasitemia/parasitologia , Receptores de Interleucina-2/genética
8.
J Comp Physiol B ; 180(5): 757-66, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20140678

RESUMO

Adult marine mammal muscles rely upon a suite of adaptations for sustained aerobic metabolism in the absence of freely available oxygen (O(2)). Although the importance of these adaptations for supporting aerobic diving patterns of adults is well understood, little is known about postnatal muscle development in young marine mammals. However, the typical pattern of vertebrate muscle development, and reduced tissue O(2) stores and diving ability of young marine mammals suggest that the physiological properties of harbor seal (Phoca vitulina) pup muscle will differ from those of adults. We examined myoglobin (Mb) concentration, and the activities of citrate synthase (CS), beta-hydroxyacyl coA dehydrogenase (HOAD), and lactate dehydrogenase (LDH) in muscle biopsies from harbor seal pups throughout the nursing period, and compared these biochemical parameters to those of adults. Pups had reduced O(2) carrying capacity ([Mb] 28-41% lower than adults) and reduced metabolically scaled catabolic enzyme activities (LDH/RMR 20-58% and CS/RMR 29-89% lower than adults), indicating that harbor seal pup muscles are biochemically immature at birth and weaning. This suggests that pup muscles do not have the ability to support either the aerobic or anaerobic performance of adult seals. This immaturity may contribute to the lower diving capacity and behavior in younger pups. In addition, the trends in myoglobin concentration and enzyme activity seen in this study appear to be developmental and/or exercise-driven responses that together work to produce the hypoxic endurance phenotype seen in adults, rather than allometric effects due to body size.


Assuntos
Mergulho/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/fisiologia , Phoca/fisiologia , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Envelhecimento/fisiologia , Animais , Animais Lactentes/crescimento & desenvolvimento , Animais Lactentes/metabolismo , Citrato (si)-Sintase/metabolismo , Feminino , L-Lactato Desidrogenase/metabolismo , Mioglobina/metabolismo , Phoca/crescimento & desenvolvimento , Desmame
9.
J Exp Biol ; 213(5): 740-8, 2010 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-20154189

RESUMO

In diving animals, skeletal muscle adaptations to extend underwater time despite selective vasoconstriction include elevated myoglobin (Mb) concentrations, high acid buffering ability (beta) and high aerobic and anaerobic enzyme activities. However, because cardiac muscle is perfused during dives, it may rely less heavily on Mb, beta and anaerobic pathways to support contractile activity. In addition, because cardiac tissue must sustain contractile activity even before birth, it may be more physiologically mature at birth and/or develop faster than skeletal muscles. To test these hypotheses, we measured Mb levels, beta and the activities of citrate synthase (CS), beta-hydroxyacyl-CoA dehydrogenase (HOAD) and lactate dehydrogenase (LDH) in cardiac and skeletal muscle samples from 72 harp and hooded seals, ranging in age from fetuses to adults. Results indicate that in adults cardiac muscle had lower Mb levels (14.7%), beta (55.5%) and LDH activity (36.2%) but higher CS (459.6%) and HOAD (371.3%) activities (all P<0.05) than skeletal muscle. In addition, while the cardiac muscle of young seals had significantly lower [Mb] (44.7%) beta (80.7%) and LDH activity (89.5%) than adults (all P<0.05), it was relatively more mature at birth and weaning than skeletal muscle. These patterns are similar to those in terrestrial species, suggesting that seal hearts do not exhibit unique adaptations to the challenges of an aquatic existence.


Assuntos
Caniformia/crescimento & desenvolvimento , Caniformia/metabolismo , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Focas Verdadeiras/crescimento & desenvolvimento , Focas Verdadeiras/metabolismo , 3-Hidroxiacil-CoA Desidrogenases/metabolismo , Aerobiose , Envelhecimento/metabolismo , Anaerobiose , Animais , Peso Corporal/fisiologia , Canadá , Locomoção , Músculo Esquelético/enzimologia , Músculo Esquelético/crescimento & desenvolvimento , Miocárdio/enzimologia , Mioglobina/metabolismo , Especificidade de Órgãos
10.
Neurology ; 74(2): 113-20, 2010 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-20065246

RESUMO

OBJECTIVE: A consistently identified risk factor for Alzheimer disease (AD) is family history of dementia, with maternal transmission significantly more frequent than paternal transmission. A history of maternal AD may be related to AD-like glucose consumption in cognitively healthy subjects. In this cross-sectional study, we tested whether cognitively healthy people with a family history of AD have less gray matter volume (GMV), an endophenotype for late-onset AD, than individuals with no family history, and whether decreases in GMV are different in subjects with a maternal family history. METHODS: As part of the Kansas University Brain Aging Project, 67 cognitively intact individuals with a maternal history of late-onset AD (FHm, n = 16), a paternal history of AD (FHp, n = 8), or no parental history of AD (FH-, n = 43), similar in age, gender, education, and Mini-Mental State Examination score, were scanned at 3 T. We used voxel-based morphometry to examine GMV differences between groups, controlling for age, gender, and apoE4. RESULTS: Cognitively healthy individuals with a family history of late-onset AD had significantly decreased GMV in the precuneus, middle frontal, inferior frontal, and superior frontal gyri compared with FH- individuals. FHm subjects had significantly smaller inferior frontal, middle frontal, precuneus, and lingual gyri compared with FH- and FHp subjects. CONCLUSIONS: Overall, maternal family history of Alzheimer disease (AD) in cognitively normal individuals is associated with lower gray matter volume in AD-vulnerable brain regions. These data complement and extend reports of cerebral metabolic differences in subjects with a maternal family history.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Atrofia/genética , Atrofia/patologia , Encéfalo/patologia , Padrões de Herança/genética , Idoso , Doença de Alzheimer/fisiopatologia , Apolipoproteína E4/genética , Atrofia/fisiopatologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Mapeamento Encefálico , Estudos de Coortes , Estudos Transversais , Diagnóstico Precoce , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mães , Testes Neuropsicológicos , Fatores de Risco
11.
J Comp Physiol B ; 179(8): 985-96, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19565249

RESUMO

Pinnipeds rely on muscle oxygen stores to help support aerobic diving, therefore muscle maturation may influence the behavioral ecology of young pinnipeds. To investigate the pattern of muscle development, myoglobin concentration ([Mb]) and acid buffering ability (beta) was measured in ten muscles from 23 harp and 40 hooded seals of various ages. Adult [Mb] ranged from 28-97 to 35-104 mg g tissue(-1) in harp and hooded seals, respectively, with values increasing from the cervical, non-swimming muscles to the main swimming muscles of the lumbar region. Neonatal and weaned pup muscles exhibited lower (approximately 30% adult values) and less variable [Mb] across the body than adults. In contrast, adult beta showed little regional variation (60-90 slykes), while high pup values (approximately 75% adult values) indicate significant in utero development. These findings suggest that intra-uterine conditions are sufficiently hypoxic to stimulate prenatal beta development, but that [Mb] development requires additional postnatal signal such as exercise, and/or growth factors. However, because of limited development in both beta and [Mb] during the nursing period, pups are weaned with muscles with lower aerobic and anaerobic capacities than those of adults.


Assuntos
Equilíbrio Ácido-Base , Envelhecimento/fisiologia , Músculo Esquelético/crescimento & desenvolvimento , Mioglobina/metabolismo , Focas Verdadeiras/metabolismo , Animais , Animais Recém-Nascidos , Oceano Atlântico , Composição Corporal , Peso Corporal , Canadá , Mergulho/fisiologia , Feminino , Groenlândia , Masculino , Desenvolvimento Muscular , Músculo Esquelético/metabolismo , Especificidade de Órgãos , Focas Verdadeiras/crescimento & desenvolvimento , Especificidade da Espécie , Fatores de Tempo , Titulometria
12.
Am J Transplant ; 9(1): 201-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18976291

RESUMO

Antibody production by normal plasma cells (PCs) against human leukocyte antigens (HLA) can be a major barrier to successful transplantation. We tested four reagents with possible activity against PCs (rituximab, polyclonal rabbit antithymocyte globulin (rATG), intravenous immunoglobulin (IVIG) and the proteasome inhibitor, bortezomib) to determine their ability to cause apoptosis of human bone marrow-derived PCs and subsequently block IgG secretion in vitro. IVIG, rituximab and rATG all failed to cause apoptosis of PCs and neither rituximab nor rATG blocked antibody production. In contrast, bortezomib treatment led to PC apoptosis and thereby blocked anti-HLA and antitetanus IgG secretion in vitro. Two patients treated with bortezomib for humoral rejection after allogeneic kidney transplantation demonstrated a transient decrease in bone marrow PCs in vivo and persistent alterations in alloantibody specificities. Total IgG levels were unchanged. We conclude that proteasome activity is important for PC longevity and its inhibition may lead to new techniques of controlling antibody production in vivo.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Borônicos/farmacologia , Inibidores de Cisteína Proteinase/farmacologia , Isoanticorpos/biossíntese , Plasmócitos/citologia , Inibidores de Proteassoma , Pirazinas/farmacologia , Especificidade de Anticorpos , Ácidos Borônicos/uso terapêutico , Bortezomib , Inibidores de Cisteína Proteinase/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Humanos , Isoanticorpos/imunologia , Transplante de Rim , Plasmócitos/imunologia , Pirazinas/uso terapêutico
13.
Am J Transplant ; 8(12): 2684-94, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18976305

RESUMO

We examined the course of donor-specific alloantibody (DSA) levels early after transplant and their relationship with acute humoral rejection (AHR) in two groups of positive crossmatch (+XM) kidney transplant recipients: High DSA group-41 recipients with a baseline T- or B-cell flow crossmatch (TFXM, BFXM) channel shift >or=300 (molecules of equivalent soluble fluorochrome units (MESF) of approximately 19 300) who underwent pretransplant plasmapheresis (PP), and Low DSA group-29 recipients with a baseline channel shift <300 who did not undergo PP. The incidence of AHR was 39% (16/41) in the High DSA group and 31% (9/29) in the Low DSA group. Overall, mean DSA levels decreased by day 4 posttransplant and remained low in patients who did not develop AHR. By day 10, DSA levels increased in patients developing AHR with 92% (23/25) of patients with a BFXM >359 (MESF of approximately 34 000) developing AHR. The BFXM and the total DSA measured by single antigen beads correlated well across a wide spectrum suggesting that either could be used for monitoring. We conclude that AHR is associated with the development of High DSA levels posttransplant and protocols aimed at maintaining DSA at lower levels may decrease the incidence of AHR.


Assuntos
Formação de Anticorpos/imunologia , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Teste de Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim/imunologia , Adolescente , Adulto , Idoso , Linfócitos B/imunologia , Linfócitos B/patologia , Creatinina/sangue , Feminino , Humanos , Transplante de Rim/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Linfócitos T/imunologia , Linfócitos T/patologia , Fatores de Tempo , Doadores de Tecidos , Adulto Jovem
14.
Neurology ; 71(3): 210-6, 2008 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-18625967

RESUMO

OBJECTIVE: To examine the correlation of cardiorespiratory fitness with brain atrophy and cognition in early-stage Alzheimer disease (AD). BACKGROUND: In normal aging physical fitness appears to mitigate functional and structural age-related brain changes. Whether this is observed in AD is not known. METHODS: Subjects without dementia (n = 64) and subjects with early-stage AD (n = 57) had MRI and standard clinical and psychometric evaluations. Peak oxygen consumption (VO(2)(peak)), the standard measure of cardiorespiratory fitness, was assessed during a graded treadmill test. Normalized whole brain volume, a brain atrophy estimate, was determined by MRI. Pearson correlation and linear regression were used to assess fitness in relation to brain volume and cognitive performance. RESULTS: Cardiorespiratory fitness (VO(2)(peak)) was modestly reduced in subjects with AD (34.7 [5.0] mL/kg/min) vs subjects without dementia (38.1 [6.3] mL/kg/min, p = 0.002). In early AD, VO(2)(peak) was associated with whole brain volume (beta = 0.35, p = 0.02) and white matter volume (beta = 0.35, p = 0.04) after controlling for age. Controlling for additional covariates of sex, dementia severity, physical activity, and physical frailty did not attenuate the relationships. VO(2)(peak) was associated with performance on delayed memory and digit symbol in early AD but not after controlling for age. In participants with no dementia, there was no relationship between fitness and brain atrophy. Fitness in participants with no dementia was associated with better global cognitive performance (r = 0.30, p = 0.02) and performance on Trailmaking A and B, Stroop, and delayed logical memory but not after controlling for age. CONCLUSIONS: Increased cardiorespiratory fitness is associated with reduced brain atrophy in Alzheimer disease (AD). Cardiorespiratory fitness may moderate AD-related brain atrophy or a common underlying AD-related process may impact both brain atrophy and cardiorespiratory fitness.


Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Teste de Esforço , Aptidão Física/fisiologia , Mecânica Respiratória/fisiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Envelhecimento/fisiologia , Doença de Alzheimer/psicologia , Atrofia , Cognição/fisiologia , Estudos Transversais , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Fatores de Tempo
15.
Am J Transplant ; 8(1): 133-43, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18184311

RESUMO

Donor-specific alloantibody presents a major barrier to the successful transplantation of kidneys and hearts. However, the study of alloantibody production has been hampered by both an inadequate source of antibody-secreting cells (ASCs) and a paucity of assays to determine their function. We describe two new assays that allow for the determination of the frequency and specificities of allo-ASCs in humans using purified HLA as targets. These assays demonstrated allo-ASCs in the CD138(+) fraction of the bone marrow, but not in peripheral blood. Alloantibody specificities in these assays correlated well with those detected in the serum suggesting that bone marrow-derived ASCs are indeed a major source of alloantibody in vivo. However, ASCs for a specific HLA antigen were rare with an estimated frequency of only 1/2 x 10(6) marrow cells. Pretransplant treatment in vivo with multiple plasmaphereses and low-dose IVIG alone or in combination with rATG had no effect on ASC number or alloantibody production. These techniques allow for the study of allospecific ASCs and provide a method to test the potential efficacy of agents on alloantibody production in vivo.


Assuntos
Células Produtoras de Anticorpos/imunologia , Soro Antilinfocitário/imunologia , Dessensibilização Imunológica , Imunoglobulinas Intravenosas , Isoanticorpos/biossíntese , Adulto , Idoso , Células Produtoras de Anticorpos/metabolismo , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Neurology ; 69(11): 1094-104, 2007 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-17846409

RESUMO

OBJECTIVE: Accumulating evidence suggests insulin and insulin signaling may be involved in the pathophysiology of Alzheimer disease (AD). The relationship between insulin-mediated glucoregulation and brain structure has not been assessed in individuals with AD. METHODS: Nondemented (Clinical Dementia Rating [CDR] 0, n = 31) and early stage AD (CDR 0.5 and 1, n = 31) participants aged 65 years and older had brain MRI to determine whole brain and hippocampal volume and 3-hour IV glucose tolerance tests to determine glucose and insulin area under the curve (AUC). Linear regression models were used to assess the relationship of insulin and glucose with brain volume, cognition, and dementia severity. RESULTS: In early AD, insulin and glucose AUCs were related to whole brain (insulin beta = 0.66, p < 0.001; glucose beta = 0.45, p < 0.01) and hippocampal volume (insulin beta = 0.42, p < 0.05; glucose beta = 0.46, p < 0.05). These relationships were independent of age, sex, body mass index, body fat, cardiorespiratory fitness, physical activity, cholesterol, and triglycerides. Insulin AUC, but not glucose, was associated with cognitive performance in early AD (beta = 0.40, p = 0.04). Insulin AUC was associated with dementia severity (Pearson r = -0.40, p = 0.03). Glucose and insulin were not related to brain volume or cognitive performance in nondemented individuals. CONCLUSIONS: Increased peripheral insulin is associated with reduced Alzheimer disease (AD)-related brain atrophy, cognitive dysfunction, and dementia severity, suggesting that insulin signaling may play a role in the pathophysiology of AD.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Complicações do Diabetes/metabolismo , Insulina/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Área Sob a Curva , Atrofia/etiologia , Atrofia/patologia , Atrofia/fisiopatologia , Glicemia/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Estudos de Coortes , Estudos Transversais , Complicações do Diabetes/patologia , Complicações do Diabetes/fisiopatologia , Progressão da Doença , Feminino , Teste de Tolerância a Glucose , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Transdução de Sinais/fisiologia , Regulação para Cima
17.
J Comp Physiol B ; 177(6): 687-700, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17576570

RESUMO

Pinnipeds rely primarily on oxygen stores in blood and muscles to support aerobic diving; therefore rapid development of body oxygen stores (TBO(2)) is crucial for pups to transition from nursing to independent foraging. Here, we investigate TBO(2) development in 45 harp (Pagophilus groenlandicus) and 46 hooded (Cystophora cristata) seals ranging in age from neonates to adult females. We found that hooded seal adults have the largest TBO(2) stores yet reported (89.5 ml kg(-1)), while harp seal adults have values more similar to other phocids (71.6 ml kg(-1)). In adults, large TBO(2) stores resulted from large blood volume (harp169, hood 194 ml kg(-1)) and high muscle Mb content (harp 86.0, hood 94.8 mg g(-1)). In contrast, pups of both species had significantly lower mass-specific TBO(2 )stores than adults, and stores declined rather than increased during the nursing period. This decline was due to a reduction in mass-specific blood volume and the absence of an increase in the low Mb levels (harp 21.0, hood 31.5 mg g(-1)). Comparisons with other phocid species suggests that the pattern of blood and muscle development in the pre- and post-natal periods varies with terrestrial period, and that muscle maturation rates may influence the length of the postweaning fast. However, final maturation of TBO(2) stores does not take place until after foraging begins.


Assuntos
Mergulho/fisiologia , Oxigênio/sangue , Oxigênio/metabolismo , Focas Verdadeiras/sangue , Focas Verdadeiras/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos/sangue , Animais Lactentes/sangue , Análise Química do Sangue/veterinária , Composição Corporal , Tamanho Corporal , Estudos Transversais , Índices de Eritrócitos/veterinária , Feminino , Testes Hematológicos/métodos , Testes Hematológicos/veterinária , Hemoglobinas/metabolismo , Músculo Esquelético/metabolismo , Mioglobina/metabolismo , Focas Verdadeiras/crescimento & desenvolvimento , Especificidade da Espécie
18.
Hernia ; 10(3): 236-42, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16453072

RESUMO

A retrospective chart review at the Carolinas Medical Center was performed on all patients who underwent laparoscopic ventral hernia repair (LVHR) from July 1998 through December 2003. LVHR was successfully completed in 270 of the 277 patients, or 98%, in whom it was attempted. Half of the patients (138/277) had at least one previous failed repair. The average defect measured 143.3 cm(2), and mesh was used in all repairs. The mean operating time was 168.3 min, mean blood loss was 50 cc, and average length of hospitalization was 3.0 days. Thirty-four complications occurred in 31 patients (11%). Only two mesh infections occurred (0.7%). At a mean follow-up period of 21 months, the rate of hernia recurrence was 4.7%. As experience grows and length of follow-up expands, LVHR may become the preferred approach for ventral hernia in difficult patients, especially obese patients and patients who have failed prior open repairs.


Assuntos
Hérnia Ventral/cirurgia , Laparoscopia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Politetrafluoretileno , Complicações Pós-Operatórias , Recidiva , Reoperação , Estudos Retrospectivos , Telas Cirúrgicas , Resultado do Tratamento
19.
Hernia ; 10(2): 120-4, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16453077

RESUMO

Although mesh use is important for effective herniorrhaphy in adults, prosthetic infections can cause serious morbidity. Bacterial adherence to the mesh is a known precursor to prosthetic infection. We compared the ability of common mesh prosthetics to resist bacterial adherence. The meshes studied included polypropylene (Marlex, expanded polytetrafluoroethylene (PTFE) with and without silver chlorhexidine coating (DualMesh Plus and Dualmesh) composite meshes (Composix E/X, Proceed, and Parietex Composite) and lightweight polypropylene meshes (TiMesh, Ultrapro, and Vypro). Fifteen samples of each mesh type were individually inoculated with a suspension of 10(8 )methicillin-resistant Staphylococcus aureus (MRSA) in tryptic soy broth. After incubation at 37 degrees C for 1 h, the mesh pieces were then removed and serially washed. The colony-forming units (CFU) of MRSA present in the initial inoculum, at the end of the 1-h warm-water bath (broth count), and the pooled washes (wash count), were determined using serial dilutions and spot plating. The bacteria not accounted for in the broth or wash counts were considered adhered to the mesh. Samples of each mesh type were also analyzed using scanning electron microscopy (SEM). Data are presented as the mean percentage adherence with ANOVA and Tukey's test used to determine significance (P<0.05). The DualMesh Plus mesh had no detectable MRSA in the broth or the pooled wash samples. Dualmesh had less adherence compared with Marlex, Proceed, and Vypro (P<0.05). Conversely, Vypro had a statistically higher adherence (96%, P<0.05) as compared to TiMesh, Ultrapro, Composix E/X, and Parietex Composite. SEM confirmed bacterial adherence to all the mesh types except DualMesh Plus. The ability of a biomaterial to resist infection has an important clinical significance. DualMesh Plus, due to its antimicrobial coating, is the only mesh type of the nine tested that demonstrated a bactericidal property. Standard PTFE (Dualmesh) also had less bacterial adherence. Vypro demonstrated an increase in bacterial adherence; this was possibly due to the multifilament polyglactin 910 weaved within the prolene component of the mesh.


Assuntos
Resistência a Meticilina , Staphylococcus aureus/crescimento & desenvolvimento , Telas Cirúrgicas/microbiologia , Aderência Bacteriana , Clorexidina , Polipropilenos , Politetrafluoretileno , Staphylococcus aureus/efeitos dos fármacos
20.
Physiol Biochem Zool ; 78(6): 1057-68, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16228944

RESUMO

Harbor seal pups are highly precocial and can swim and dive at birth. Such behavioral maturity suggests that they may be born with mature body oxygen stores or that stores develop quickly during the nursing period. To test this hypothesis, we compared the blood and muscle oxygen stores of harbor seal pups, yearlings, and adults. We found that pups had smaller oxygen stores than adults (neonates 57%, weaned pups 75%, and yearlings 90% those of adults), largely because neonatal myoglobin concentrations were low (1.6+/-0.2 g% vs. 3.8+/-0.3 g% for adults) and changed little during the nursing period. In contrast, blood oxygen stores were relatively mature, with nursing pups having hematocrit (55%+/-0.2%), hemoglobin (21.7+/-0.4 g%), and blood volume (12.3+/-0.5 mL/kg) only slightly lower than the corresponding values for adults (57%+/-0.2%, 23.8+/-0.3 g %, and 15.0+/-0.5 mL/kg). Because neonatal pups had relatively high metabolic rates (11.0 mL O2/kg min), their calculated aerobic dive limit was less than 50% that of adults. These results suggest that harbor seals' early aquatic activity is primarily supported by rapid development of blood, with immature muscle oxygen stores and elevated use rates limiting aerobic diving ability.


Assuntos
Metabolismo Energético/fisiologia , Oxigênio/sangue , Oxigênio/metabolismo , Phoca/metabolismo , Fatores Etários , Animais , Composição Corporal , Tamanho Corporal , Hematócrito , Hemoglobinas , Modelos Lineares , Músculo Esquelético/metabolismo , Phoca/fisiologia
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