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1.
AJNR Am J Neuroradiol ; 44(6): 700-706, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37142433

RESUMO

BACKGROUND AND PURPOSE: Children with spastic cerebral palsy have motor deficits associated with periventricular leukomalacia indicating WM damage to the corticospinal tracts. We investigated whether practice of skilled lower extremity selective motor control movements would elicit neuroplasticity. MATERIALS AND METHODS: Twelve children with spastic bilateral cerebral palsy and periventricular leukomalacia born preterm (mean age, 11.5 years; age range, 7.3-16.6 years) participated in a lower extremity selective motor control intervention, Camp Leg Power. Activities promoted isolated joint movement including isokinetic knee exercises, ankle-controlled gaming, gait training, and sensorimotor activities (3 hours/day, 15 sessions, 1 month). DWI scans were collected pre- and postintervention. Tract-Based Spatial Statistics was used to analyze changes in fractional anisotropy, radial diffusivity, axial diffusivity, and mean diffusivity. RESULTS: Significantly reduced radial diffusivity (P < . 05) was found within corticospinal tract ROIs, including 28.4% of the left and 3.6% of the right posterior limb of the internal capsule and 14.1% of the left superior corona radiata. Reduced mean diffusivity was found within the same ROIs (13.3%, 11.6%, and 6.6%, respectively). Additionally, decreased radial diffusivity was observed in the left primary motor cortex. Additional WM tracts had decreased radial diffusivity and mean diffusivity, including the anterior limb of the internal capsule, external capsule, anterior corona radiata, and corpus callosum body and genu. CONCLUSIONS: Myelination of the corticospinal tracts improved following Camp Leg Power. Neighboring WM changes suggest recruitment of additional tracts involved in regulating neuroplasticity of the motor regions. Intensive practice of skilled lower extremity selective motor control movements promotes neuroplasticity in children with spastic bilateral cerebral palsy.


Assuntos
Paralisia Cerebral , Leucomalácia Periventricular , Substância Branca , Recém-Nascido , Humanos , Criança , Adolescente , Paralisia Cerebral/complicações , Paralisia Cerebral/diagnóstico por imagem , Imagem de Tensor de Difusão , Perna (Membro) , Espasticidade Muscular , Extremidade Inferior , Anisotropia
2.
BMC Biol ; 20(1): 244, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36310170

RESUMO

BACKGROUND: Animals can exhibit remarkable reproductive plasticity in response to their social surroundings, with profound fitness consequences. The presence of same-sex conspecifics can signal current or future expected competition for resources or mates. Plastic responses to elevated sexual competition caused by exposure to same-sex individuals have been well-studied in males. However, much less is known about such plastic responses in females, whether this represents sexual or resource competition, or if it leads to changes in investment in mating behaviour and/or reproduction. Here, we used Drosophila melanogaster to measure the impact of experimentally varying female exposure to other females prior to mating on fecundity before and after mating. We then deployed physical and genetic methods to manipulate the perception of different social cues and sensory pathways and reveal the potential mechanisms involved. RESULTS: The results showed that females maintained in social isolation prior to mating were significantly more likely to retain unfertilised eggs before mating, but to show the opposite and lay significantly more fertilised eggs in the 24h after mating. More than 48h of exposure to other females was necessary for this social memory response to be expressed. Neither olfactory nor visual cues were involved in mediating fecundity plasticity-instead, the relevant cues were perceived through direct contact with the non-egg deposits left behind by other females. CONCLUSIONS: The results demonstrate that females show reproductive plasticity in response to their social surroundings and can carry this memory of their social experience forward through mating. Comparisons of our results with previous work show that the nature of female plastic reproductive responses and the cues they use differ markedly from those of males. The results emphasise the deep divergence in how each sex realises its reproductive success.


Assuntos
Drosophila melanogaster , Comportamento Sexual Animal , Animais , Masculino , Feminino , Comportamento Sexual Animal/fisiologia , Drosophila melanogaster/fisiologia , Reprodução/fisiologia , Fertilidade , Percepção
3.
AJNR Am J Neuroradiol ; 42(11): 2054-2061, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34593378

RESUMO

BACKGROUND AND PURPOSE: Selective voluntary motor control is an important factor influencing gross motor function, interjoint coordination, and the outcome of hamstring-lengthening surgery in spastic cerebral palsy. Using DTI, we investigated whether selective voluntary motor control would show strong correlations with WM motor tract microstructure and whether selective voluntary motor control is more sensitive to global WM impairment than gross motor function. MATERIALS AND METHODS: Children with spastic bilateral cerebral palsy born preterm and typically developing children were recruited. The Selective Control Assessment of the Lower Extremity (SCALE) and Gross Motor Function Measure (GMFM) were assessed in participants with cerebral palsy. Participants underwent brain MR imaging to collect DWI data. Tract-Based Spatial Statistics was used to analyze the WM for between-group differences and correlations with SCALE and GMFM. ROI analyses compared motor regions. RESULTS: Twelve children with cerebral palsy (mean age, 11.5 years) and 12 typically developing children (mean age, 10.3 years) participated. Altered DTI outcomes were found throughout the whole brain for the cerebral palsy group. SCALE, developed to evaluate selective voluntary motor control in cerebral palsy, showed significant positive correlations with fractional anisotropy in more WM voxels throughout the whole brain and for motor regions, including the corticospinal tract and corpus callosum, compared with GMFM. A significant negative correlation between radial diffusivity and SCALE, but not GMFM, was found within the corpus callosum. CONCLUSIONS: SCALE was a more sensitive clinical correlate of motor and whole-brain WM tract impairment in children with spastic bilateral cerebral palsy, suggesting greater anisotropy and myelination in these regions for those with higher selective voluntary motor control.


Assuntos
Paralisia Cerebral , Substância Branca , Encéfalo/diagnóstico por imagem , Paralisia Cerebral/diagnóstico por imagem , Criança , Imagem de Tensor de Difusão , Humanos , Recém-Nascido , Espasticidade Muscular
5.
J Eur Acad Dermatol Venereol ; 34(7): 1449-1456, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32012384

RESUMO

Immunosuppressive therapies, effective in treating inflammatory disorders such as psoriasis, increase the risk of serious infections, such as tuberculosis (TB). For example, tumour necrosis factor (TNF)-alpha inhibitors significantly increase the risk of TB reactivation in patients with latent TB infection (LTBI), which has led clinicians to routinely test for TB prior to initiation of these medications. This protocol has since extended to other, newer immunomodulatory therapies for psoriasis, such as interleukin (IL)-17 inhibitors, including secukinumab, ixekizumab and brodalumab. We conducted a systematic review to examine whether there is any evidence that IL-17 inhibitor therapy for psoriasis increases the risk of TB reactivation. Using PubMed and EMBASE, our literature search resulted in 139 total articles. After manually reviewing each article for the discussion of IL-17 inhibitors for psoriasis, with data originating from clinical trials, and assessment for incidence of TB reactivation, 23 articles met the full inclusion criteria for our review. Overall, we found no cases of TB reactivation in patients treated with IL-17 inhibitors for psoriasis. This suggests that IL-17 inhibitors may be safely used in psoriasis patients with LTBI who receive appropriate LTBI treatment. However, long-term real-world studies are warranted to further evaluate this risk.


Assuntos
Tuberculose Latente , Psoríase , Tuberculose , Humanos , Fatores Imunológicos , Imunossupressores , Interleucina-17 , Tuberculose Latente/induzido quimicamente , Tuberculose Latente/epidemiologia , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Tuberculose/induzido quimicamente , Tuberculose/epidemiologia
6.
Prev Vet Med ; 126: 159-69, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26907209

RESUMO

Viruses play a key role in the complex aetiology of bovine respiratory disease (BRD). Bovine viral diarrhoea virus 1 (BVDV-1) is widespread in Australia and has been shown to contribute to BRD occurrence. As part of a prospective longitudinal study on BRD, effects of exposure to BVDV-1 on risk of BRD in Australian feedlot cattle were investigated. A total of 35,160 animals were enrolled at induction (when animals were identified and characteristics recorded), held in feedlot pens with other cattle (cohorts) and monitored for occurrence of BRD over the first 50days following induction. Biological samples collected from all animals were tested to determine which animals were persistently infected (PI) with BVDV-1. Data obtained from the Australian National Livestock Identification System database were used to determine which groups of animals that were together at the farm of origin and at 28days prior to induction (and were enrolled in the study) contained a PI animal and hence to identify animals that had probably been exposed to a PI animal prior to induction. Multi-level Bayesian logistic regression models were fitted to estimate the effects of exposure to BVDV-1 on the risk of occurrence of BRD. Although only a total of 85 study animals (0.24%) were identified as being PI with BVDV-1, BVDV-1 was detected on quantitative polymerase chain reaction in 59% of cohorts. The PI animals were at moderately increased risk of BRD (OR 1.9; 95% credible interval 1.0-3.2). Exposure to BVDV-1 in the cohort was also associated with a moderately increased risk of BRD (OR 1.7; 95% credible interval 1.1-2.5) regardless of whether or not a PI animal was identified within the cohort. Additional analyses indicated that a single quantitative real-time PCR test is useful for distinguishing PI animals from transiently infected animals. The results of the study suggest that removal of PI animals and/or vaccination, both before feedlot entry, would reduce the impact of BVDV-1 on BRD risk in cattle in Australian feedlots. Economic assessment of these strategies under Australian conditions is required.


Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina/epidemiologia , Vírus da Diarreia Viral Bovina Tipo 1 , Ração Animal/virologia , Criação de Animais Domésticos , Animais , Anticorpos Antivirais/sangue , Doença das Mucosas por Vírus da Diarreia Viral Bovina/diagnóstico , Doença das Mucosas por Vírus da Diarreia Viral Bovina/prevenção & controle , Doença das Mucosas por Vírus da Diarreia Viral Bovina/transmissão , Bovinos , Estudos de Coortes , Vírus da Diarreia Viral Bovina Tipo 1/genética , Vírus da Diarreia Viral Bovina Tipo 1/isolamento & purificação , Prevalência , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Fatores de Risco , Vacinas Virais/administração & dosagem
7.
Med Phys ; 42(2): 623-36, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25652480

RESUMO

PURPOSE: The authors are developing a system for calibrated breast density measurements using full field digital mammography (FFDM). Breast tissue equivalent (BTE) phantom images are used to establish baseline (BL) calibration curves at time zero. For a given FFDM unit, the full BL dataset is comprised of approximately 160 phantom images, acquired prior to calibrating prospective patient mammograms. BL curves are monitored serially to ensure they produce accurate calibration and require updating when calibration accuracy degrades beyond an acceptable tolerance, rather than acquiring full BL datasets repeatedly. BL updating is a special case of generalizing calibration datasets across FFDM units, referred to as cross-calibration. Serial monitoring, BL updating, and cross-calibration techniques were developed and evaluated. METHODS: BL curves were established for three Hologic Selenia FFDM units at time zero. In addition, one set of serial phantom images, comprised of equal proportions of adipose and fibroglandular BTE materials (50/50 compositions) of a fixed height, was acquired biweekly and monitored with the cumulative sum (Cusum) technique. These 50/50 composition images were used to update the BL curves when the calibration accuracy degraded beyond a preset tolerance of ±4 standardized units. A second set of serial images, comprised of a wide-range of BTE compositions, was acquired biweekly to evaluate serial monitoring, BL updating, and cross-calibration techniques. RESULTS: Calibration accuracy can degrade serially and is a function of acquisition technique and phantom height. The authors demonstrated that all heights could be monitored simultaneously while acquiring images of a 50/50 phantom with a fixed height for each acquisition technique biweekly, translating into approximately 16 image acquisitions biweekly per FFDM unit. The same serial images are sufficient for serial monitoring, BL updating, and cross-calibration. Serial calibration accuracy was maintained within ±4 standardized unit variation from the ideal when applying BL updating. BL updating is a special case of cross-calibration; the BL dataset of unit 1 can be converted to the BL dataset for another similar unit (i.e., unit 2) at any given time point using the 16 serial monitoring 50/50 phantom images of unit 2 (or vice versa) acquired near this time point while maintaining the ±4 standardized unit tolerance. CONCLUSIONS: A methodology for monitoring and maintaining serial calibration accuracy for breast density measurements was evaluated. Calibration datasets for a given unit can be translated forward in time with minimal phantom imaging effort. Similarly, cross-calibration is a method for generalizing calibration datasets across similar units without additional phantom imaging. This methodology will require further evaluation with mammograms for complete validation.


Assuntos
Mama/citologia , Mamografia/métodos , Intensificação de Imagem Radiográfica/métodos , Calibragem , Humanos , Imagens de Fantasmas , Controle de Qualidade
8.
Aust Vet J ; 92(6): 185-91, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24862996

RESUMO

BACKGROUND: Bovine respiratory disease complex (BRDC) is a multi-factorial disease in which numerous factors, such as animal management, pathogen exposure and environmental conditions, contribute to the development of acute respiratory illness in feedlot cattle. The role of specific pathogens in the development of BRDC has been difficult to define because of the complex nature of the disease and the presence of implicated bacterial pathogens in the upper respiratory tract of healthy animals. Mycoplasma bovis is an important pathogen of cattle and recognised as a major contributor to cases of mastitis, caseonecrotic bronchopneumonia, arthritis and otitis media. To date, the role of M. bovis in the development of BRDC of Australian feeder cattle has not been investigated. METHODS: In this review, the current literature pertaining to the role of M. bovis in BRDC is evaluated. In addition, preliminary data are presented that identify M. bovis as a potential contributor to BRDC in Australian feedlots, which has not been considered previously. RESULTS AND CONCLUSION: The preliminary results demonstrate detection of M. bovis in samples from all feedlots studied. When considered in the context of the reviewed literature, they support the inclusion of M. bovis on the list of pathogens to be considered during investigations into BRDC in Australia.


Assuntos
Complexo Respiratório Bovino , Mycoplasma bovis , Animais , Austrália , Complexo Respiratório Bovino/diagnóstico , Complexo Respiratório Bovino/microbiologia , Complexo Respiratório Bovino/prevenção & controle , Bovinos , Europa (Continente) , Infecções por Mycoplasma/veterinária , Mycoplasma bovis/isolamento & purificação , América do Norte , Fatores de Risco
9.
Med Phys ; 40(11): 113502, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24320473

RESUMO

PURPOSE: The Breast Imaging Reporting and Data System (BI-RADS) breast composition descriptors are used for standardized mammographic reporting and are assessed visually. This reporting is clinically relevant because breast composition can impact mammographic sensitivity and is a breast cancer risk factor. New techniques are presented and evaluated for generating automated BI-RADS breast composition descriptors using both raw and calibrated full field digital mammography (FFDM) image data. METHODS: A matched case-control dataset with FFDM images was used to develop three automated measures for the BI-RADS breast composition descriptors. Histograms of each calibrated mammogram in the percent glandular (pg) representation were processed to create the new BR(pg) measure. Two previously validated measures of breast density derived from calibrated and raw mammograms were converted to the new BR(vc) and BR(vr) measures, respectively. These three measures were compared with the radiologist-reported BI-RADS compositions assessments from the patient records. The authors used two optimization strategies with differential evolution to create these measures: method-1 used breast cancer status; and method-2 matched the reported BI-RADS descriptors. Weighted kappa (κ) analysis was used to assess the agreement between the new measures and the reported measures. Each measure's association with breast cancer was evaluated with odds ratios (ORs) adjusted for body mass index, breast area, and menopausal status. ORs were estimated as per unit increase with 95% confidence intervals. RESULTS: The three BI-RADS measures generated by method-1 had κ between 0.25-0.34. These measures were significantly associated with breast cancer status in the adjusted models: (a) OR = 1.87 (1.34, 2.59) for BR(pg); (b) OR = 1.93 (1.36, 2.74) for BR(vc); and (c) OR = 1.37 (1.05, 1.80) for BR(vr). The measures generated by method-2 had κ between 0.42-0.45. Two of these measures were significantly associated with breast cancer status in the adjusted models: (a) OR = 1.95 (1.24, 3.09) for BR(pg); (b) OR = 1.42 (0.87, 2.32) for BR(vc); and (c) OR = 2.13 (1.22, 3.72) for BR(vr). The radiologist-reported measures from the patient records showed a similar association, OR = 1.49 (0.99, 2.24), although only borderline statistically significant. CONCLUSIONS: A general framework was developed and validated for converting calibrated mammograms and continuous measures of breast density to fully automated approximations for the BI-RADS breast composition descriptors. The techniques are general and suitable for a broad range of clinical and research applications.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Mama/patologia , Mamografia/métodos , Algoritmos , Automação , Calibragem , Estudos de Casos e Controles , Feminino , Humanos , Mamografia/normas , Razão de Chances , Probabilidade , Interpretação de Imagem Radiográfica Assistida por Computador , Análise de Regressão , Reprodutibilidade dos Testes , Fatores de Risco
10.
Gut ; 57(7): 903-10, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18305068

RESUMO

BACKGROUND AND AIMS: Reduced ileal Paneth cell alpha-defensin expression has been reported to be associated with Crohn's disease, especially in patients carrying NOD2 mutations. The aim of this study was to independently assess whether NOD2, alpha-defensins and Crohn's disease are linked. METHODS: Using quantitative real-time polymerase chain reaction (RT-PCR), we measured the mRNA expression levels of key Paneth cell antimicrobial peptides (DEFA5, DEFA6, LYZ, PLA2G2A), inflammatory cytokines [interkelukin 6 (IL6) and IL8], and a marker of epithelial cell content, villin (VIL1) in 106 samples from both affected ileum (inflamed Crohn's disease cases, n = 44) and unaffected ileum (non-inflamed; Crohn's disease cases, n = 51 and controls, n = 11). Anti-human defensin 5 (HD-5) and haematoxylin/eosin immunohistochemical staining was performed on parallel sections from NOD2 wild-type and NOD2 mutant ileal Crohn's disease tissue. RESULTS: In Crohn's disease patients, DEFA5 and DEFA6 mRNA expression levels were 1.9- and 2.2-fold lower, respectively, in histologically confirmed inflamed ileal mucosa after adjustment for confounders (DEFA5, p<0.001; DEFA6, p = 0.001). In contrast to previous studies, we found no significant association between alpha-defensin expression and NOD2 genotype. HD-5 protein data supports these RNA findings. The reduction in HD-5 protein expression appears due to surface epithelial cell loss and reduced Paneth cell numbers as a consequence of tissue damage. CONCLUSIONS: Reduction in alpha-defensin expression is independent of NOD2 status and is due to loss of surface epithelium as a consequence of inflammatory changes rather than being the inciting event prior to inflammation in ileal Crohn's disease.


Assuntos
Doença de Crohn/metabolismo , Íleo/metabolismo , Proteína Adaptadora de Sinalização NOD2/genética , alfa-Defensinas/metabolismo , Adulto , Idoso , Doença de Crohn/genética , Doença de Crohn/imunologia , Feminino , Expressão Gênica , Genótipo , Fosfolipases A2 do Grupo II/genética , Fosfolipases A2 do Grupo II/metabolismo , Humanos , Técnicas Imunoenzimáticas , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Muramidase/genética , Muramidase/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Celulas de Paneth/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , alfa-Defensinas/genética
11.
Neurology ; 70(2): 137-43, 2008 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-17942817

RESUMO

BACKGROUND: Albuterol is a beta-2 agonist that has been demonstrated to increase muscle strength in studies in animals and humans. Based on a pilot study of extended-release albuterol Repetabs in children with dystrophinopathies, the authors conducted a randomized, double-blind, placebo-controlled study with a crossover design. METHODS: Fourteen boys with Duchenne or Becker muscular dystrophy, 6 to 11 years old, completed two treatment periods (albuterol and placebo), 12 weeks each, separated by a 12-week washout period. As the albuterol Repetab formulation was no longer available, an alternate extended release albuterol was used (Volmax, 12 mg per day). Outcome measurements included 1) lean body mass, 2) fat mass, 3) isometric knee extensor and flexor moments, 4) manual muscle testing, and 5) timed functional tests. RESULTS: Lean body mass was significantly higher for subjects following albuterol treatment compared to placebo treatment, while fat mass was significantly lower. No differences were found in isometric knee moments or manual muscle tests. Time to run/walk 30 feet was improved following albuterol. CONCLUSIONS: Short-term treatment with extended release albuterol may increase lean body mass, decrease fat mass, and improve functional measures in patients with dystrophinopathies. However, the significant change in strength of specific muscle groups found in the pilot study was not observed in the present study. These findings may be attributed to differences in the drug release and kinetics between Repetab and Volmax formulations as they affect the concentration of available beta-2 receptors on the muscle cell surface differently.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Índice de Massa Corporal , Criança , Método Duplo-Cego , Humanos , Masculino
12.
J Med Genet ; 43(10): e51, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17047091

RESUMO

BACKGROUND: Angiotensin peptides may act locally as cytokines in several organ systems with elevated mucosal levels present in Crohn's disease. A variant in the angiotensinogen gene promoter results in increased peptide production, while transforming growth factor beta1 (TGFbeta1) codon 25 variants demonstrate variable peptide production, predisposing to fibrosis in several organs. AIMS: Conduct an Australian-based analysis of the angiotensinogen-6 variant in two independent inflammatory bowel disease (IBD) cohorts, and examine the role of angiotensinogen-6 and TGFbeta1 codon 25 variants in shaping Crohn's disease phenotype. METHODS: IBD Patients (Crohn's disease = 347, ulcerative colitis = 147) and CD families (n = 148) from two cohorts, together with 185 healthy controls were genotyped for angiotensinogen-6. Genotype-phenotype analyses were performed for both angiotensinogen-6 and TGFbeta1 codon 25. RESULTS: Angiotensinogen-6 AA genotype was significantly associated with Crohn's disease (p = 0.007, OR = 2.38, CI = 1.32-4.32) in cohort 1, but not in the smaller cohort 2 (p = 0.19). The association remained significant when the two cohorts were combined (p = 0.008), and in a TDT family analysis (p = 0.03). TGF 1 codon 25 was associated with stricturing Crohn's disease (p = 0.01, OR = 2.63, CI = 1.16-5.88) and a shorter time to intestinal resection (p = 0.06). CONCLUSIONS: The association of the angiotensinogen-6 variant with Crohn's disease supports a potential role for angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists in disease treatment.


Assuntos
Angiotensinogênio/genética , Doença de Crohn/epidemiologia , Doença de Crohn/genética , Fator de Crescimento Transformador beta1/genética , Adolescente , Adulto , Angiotensinogênio/fisiologia , Austrália/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Colite Ulcerativa/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Desequilíbrio de Ligação , Masculino , Fenótipo , Polimorfismo Genético , Regiões Promotoras Genéticas , Fator de Crescimento Transformador beta1/fisiologia
13.
J Med Genet ; 42(6): 523-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15937090

RESUMO

BACKGROUND: The cytokines tumour necrosis factor (TNF)alpha and interleukin (IL)10 have been implicated in the pathogenesis of Crohn's disease (CD), with increased concentrations reported in patients with active disease. However, limited data exist on their effects on disease phenotype in the same population. Certain single nucleotide polymorphisms (SNPs) within the promoter region of the IL10 (-1082G/A, -592C/A) and TNFalpha (-308G/A, -857C/T) genes have been associated with altered levels of circulating IL10 and TNFalpha. METHODS: We conducted an Australian based case-control study (304 CD patients; 231 healthy controls) of these four SNPs. Further investigation of two SNPs was conducted using a logistic regression analysis. RESULTS: We identified a possible association of both IL10 SNPs and TNFalpha-857 with CD. Further investigation of a relationship with disease severity showed a significant association of higher producing IL10-1082G and TNFalpha-857C alleles with stricturing behaviour, which was strongest when these alleles were combined and persisted after multivariate analysis (p = 0.007; odds ratio (OR) 2.37, 95% CI 1.26 to 4.43). In addition, the TNFalpha-857CC genotype was independently associated with familial CD (p = 0.03; OR 3.12; 95% CI 1.15 to 8.46). CONCLUSION: These two SNPs may help to predict disease behaviour in CD patients, which may be clinically useful in shaping treatment of the disease at an earlier stage.


Assuntos
Doença de Crohn/diagnóstico , Doença de Crohn/genética , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Fator de Necrose Tumoral alfa/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , Fenótipo
14.
Neurology ; 62(6): 1006-8, 2004 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-15037714

RESUMO

The authors conducted a randomized, crossover, double-blind, placebo-controlled pilot study of albuterol in nine boys with dystrophinopathies. Primary outcomes were 1) isometric knee extensor and flexor strength; and 2) manual muscle testing (MMT). Isometric knee extensor strength and MMT scores were significantly higher in patients taking albuterol vs placebo. Therefore, 12-week treatment with extended-release albuterol may increase strength in patients with dystrophinopathies. A larger, double-blind, randomized study is necessary to confirm these results.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Albuterol/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Criança , Estudos Cross-Over , Método Duplo-Cego , Distrofina/genética , Seguimentos , Humanos , Contração Isométrica/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Distrofia Muscular de Duchenne/genética , Mutação , Projetos Piloto , Resultado do Tratamento
15.
Acta Neurochir (Wien) ; 143(9): 865-72, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11685618

RESUMO

OBJECTIVE: Selective Posterior Rhizotomy (SPR) is effective for reducing spasticity in children with cerebral palsy (CP). Nonetheless, extensive sensory deafferentation associated with this procedure can lead to prolonged postoperative hypotonia that delays the functional recovery of the patient. As lumbar rhizotomy provokes suprasegmental hypotonia, we hypothesized that reducing the extent of the deafferentation to the roots of L4-S1 levels would reduce the risk of postoperative hypotonia. METHODS AND RESULTS: Five patients with spastic cerebral palsy (4 males and 1 females, age range: 4-12 years) underwent limited selective dorsal rhizotomy (LSDR) of three (L4-S1) dorsal roots. All patients were able to walk independently prior to surgery. Functional assessments of these patients were performed pre and post operatively. Assessments included spasticity evaluation, passive range of motion, and sagittal plane kinematics of the hip, knee, and ankle during walking. Following surgery, reduced spasticity, increased passive range of motion and improved joint motion during walking was observed. Specifically, peak hip and knee extension and peak ankle dorsiflexion increased while peak plantarflexion decreased. CONCLUSIONS: Strength and motor control were not adversely affected by this procedure in any of the subjects and all patients actually demonstrated improvements. Previous studies have demonstrated that LSDR is highly effective in reducing spasticity and achieving functional outcome in spastic children. The results of this study demonstrated improved function during walking as assessed using gait analysis techniques.


Assuntos
Paralisia Cerebral/cirurgia , Hipotonia Muscular/etiologia , Recuperação de Função Fisiológica/fisiologia , Rizotomia/efeitos adversos , Assistência Ambulatorial , Articulação do Tornozelo/fisiopatologia , Fenômenos Biomecânicos , Paralisia Cerebral/fisiopatologia , Criança , Pré-Escolar , Feminino , Marcha/fisiologia , Articulação do Quadril/fisiopatologia , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Atividade Motora/fisiologia , Hipotonia Muscular/fisiopatologia , Espasticidade Muscular/fisiopatologia , Espasticidade Muscular/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Estudos Prospectivos , Amplitude de Movimento Articular/fisiologia
16.
Infect Immun ; 69(10): 6503-10, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11553595

RESUMO

We have identified novel adjuvant activity in specific cytosol fractions from trophozoites of Giardia isolate BRIS/95/HEPU/2041 (J. A. Upcroft, P. A. McDonnell, and P. Upcroft, Parasitol. Today, 14:281-284, 1998). Adjuvant activity was demonstrated in the systemic and mucosal compartments when Giardia extract was coadministered orally with antigen to mice. Enhanced antigen-specific serum antibody responses were demonstrated by enzyme-linked immunosorbent assay to be comparable to those generated by the "gold standard," mucosal adjuvant cholera toxin. A source of adjuvant activity was localized to the cytosolic component of the parasite. Fractionation of the cytosol produced fraction pools, some of which, when coadministered with antigen, stimulated an enhanced antigen-specific serum response. The toxic component of conventional mucosal adjuvants is associated with adjuvant activity; therefore, in a similar way, the toxin-like attributes of BRIS/95/HEPU/2041 may be responsible for its adjuvanticity. Complete characterization of the adjuvant is under way.


Assuntos
Adjuvantes Imunológicos , Antígenos/imunologia , Giardia/imunologia , Haptenos/imunologia , Hemocianinas/imunologia , Orthomyxoviridae/imunologia , Administração Oral , Animais , Anticorpos/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Formação de Anticorpos , Fracionamento Celular , Citosol/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA
18.
J Periodontol ; 72(8): 1084-91, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11525442

RESUMO

BACKGROUND: Severe periodontal furcation invasion has long been a treatment dilemma for the clinician. Many techniques have been advocated in the treatment of multi-rooted posterior teeth ranging from conventional scaling and root planing (SRP), apically positioned flaps, root amputations, root resections, tunnel procedures, guided tissue regeneration, and restorations. The keys to success depend on the clinician's ability to access the furcation to remove local factors and create an environment that enhances the patient's own hygiene efforts. Long-term success in treating teeth with furcation invasion depends upon tooth retention and arresting the destructive processes within the furcation area. METHODS: A Class III furcation invasion in a mandibular molar was treated by surgical access for SRP along with obliterating the furcation utilizing a resin ionomer restoration. RESULTS: Initially, the patient was asymptomatic. Within 3 months of treatment, the patient presented with suppuration that was refractory to local efforts. Radiographs taken only 5 months postsurgery demonstrated advanced bone loss apical to the restoration. The tooth ultimately was extracted because mobility increased and the tooth became symptomatic. CONCLUSIONS: The clinician must consider the multi-factorial etiology of periodontal breakdown within a furcation. For this patient, the technique of sealing off the exposed furcation with restorative material appeared to have resulted in progressive bone loss and accelerate tooth loss. This single case report is presented as a rebuttal to recently published articles, which have demonstrated excellent results when treating furcations with ionomer restorations.


Assuntos
Perda do Osso Alveolar/etiologia , Falha de Restauração Dentária , Restauração Dentária Permanente/efeitos adversos , Defeitos da Furca/complicações , Defeitos da Furca/terapia , Cimentos de Ionômeros de Vidro , Resinas Sintéticas , Adulto , Restauração Dentária Permanente/métodos , Humanos , Masculino , Mandíbula , Dente Molar , Perda de Dente/etiologia
19.
Phys Ther ; 81(6): 1215-23, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11380277

RESUMO

BACKGROUND AND PURPOSE: The Bobath neurodevelopmental treatment approach advised against the use of resistive exercise, as proponents felt that increased effort would increase spasticity. The purpose of this study was to test the premise that the performance of exercises with maximum efforts will increase spasticity in people with cerebral palsy (CP). Spasticity, in the present study, was defined as a velocity-dependent hyperexcitability of the muscle stretch reflex. SUBJECTS: Twenty-four subjects with the spastic diplegic form of CP (mean age=11.4 years, SD=3.0, range=7-17) and 12 subjects without known neurological impairments (mean age=11.6 years, SD=3.5, range=7-17) were assessed. METHODS: Knee muscle spasticity was assessed bilaterally using the pendulum test to elicit a stretch reflex immediately before and after 3 different forms of right quadriceps femoris muscle exercise (isometric, isotonic, and isokinetic) during a single bout of exercise training. Pendulum test outcome measures were: (1) first swing excursion, (2) number of lower leg oscillations, and (3) duration of the oscillations. RESULTS: There were no changes in spasticity following exercise between the 2 groups of subjects. DISCUSSION AND CONCLUSION: These results do not support the premise that exercises with maximum efforts increase spasticity in people with CP.


Assuntos
Paralisia Cerebral/reabilitação , Terapia por Exercício/métodos , Contração Muscular , Modalidades de Fisioterapia/métodos , Adolescente , Paralisia Cerebral/diagnóstico , Criança , Intervalos de Confiança , Eletromiografia , Feminino , Humanos , Masculino , Espasticidade Muscular/diagnóstico , Espasticidade Muscular/reabilitação , Músculo Esquelético , Probabilidade , Valores de Referência , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do Tratamento
20.
Mil Med ; 166(1): 85-9, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11197106

RESUMO

Periodontal diseases are oral disorders characterized by inflammation of the supporting tissues of the teeth. Usually, periodontitis is a progressively destructive loss of bone and periodontal ligament (loss of the attachment apparatus of the teeth). Periodontitis has documented risk factors, including but not limited to specific plaque bacteria, smoking, and diabetes mellitus. Initially, the link between systemic disease and periodontal diseases was thought to be unidirectional. Currently, there is increasing evidence that the relationship between these entities may be bidirectional. Recent case-control and cross-sectional studies indicate that periodontitis may confer a 7-fold increase in risk for preterm low birth weight infants and a 2-fold increase in risk for cardiovascular disease. These early reports indicate the potential association between systemic and oral health. Additionally, these studies support the central hypothesis that periodontal disease involves both a local and a systemic host inflammatory response. This knowledge of disease interrelationships may prove vital in intervention strategies to reduce patient risks and prevent systemic disease outcomes. Based on the current evidence of the periodontal-systemic disease connection, the purpose of this report is to help establish the groundwork for closer communication between physicians and periodontists in the military health care setting.


Assuntos
Doenças Periodontais/etiologia , Doenças Cardiovasculares/complicações , Estudos de Casos e Controles , Estudos Transversais , Placa Dentária/complicações , Complicações do Diabetes , Progressão da Doença , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Inflamação , Odontologia Militar , Doenças Periodontais/epidemiologia , Doenças Periodontais/prevenção & controle , Prevalência , Fatores de Risco , Fumar/efeitos adversos
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