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1.
Tech Coloproctol ; 22(3): 209-214, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29546469

RESUMO

BACKGROUND: The aim of the present study was to evaluate the subjective outcome of primary repair of obstetric anal sphincter injury (OASIS) at 6 months, the factors associated with the symptoms of anal incontinence (AI), and the role of a simple survey consisting in one question with three answer choices, combined with the Wexner incontinence score for the assessment of this patient population. METHODS: A retrospective cohort study was conducted on patients with third- or fourth-degree OASIS operated on between January 2007 and December 2013 inclusive at Tampere University Hospital, Finland. At 6 months, the patients were asked to report their Wexner's score as well as the three-choice assessment regarding AI symptoms. Based on this assessment, the patients were divided into three groups: those, asymptomatic, those with mild symptoms who did not want further treatment and those with severe symptoms who were willing to undergo further evaluation and treatment. RESULTS: There were 325 patients (median age 30 years). A total of 310 patients answered the questionnaire. Of which, one hundred and ninety-eight (63.9%) patients were asymptomatic, 85 (27.4%) had mild AI, and 27 (8.7%) experienced severe symptoms. There was no statistical difference in the results between the two techniques used (overlapping vs. end-to-end), or the stage of specialization of the operating physician. Persistent symptoms were associated with instrumental vaginal delivery (OR 2.12, 95% CI 1.32-3.41), severity of the injury (OR 1.64, 95% CI 1.20-2.25), and increased maternal age (OR 1.07, 95% CI 1.02-1.13). The correlation between the three-choice symptom evaluation and the Wexner score was good (Spearman's rho 0.82). CONCLUSIONS: After 6 months, severe symptoms after OASIS repair were present in 9% of women and were more frequent in older women, women with high-degree tears and after instrumental vaginal delivery. A three-choice assessment of AI symptoms correlated well with the Wexner score and might be useful to triage patients who need further evaluation.


Assuntos
Canal Anal/lesões , Canal Anal/cirurgia , Parto Obstétrico/efeitos adversos , Incontinência Fecal/etiologia , Índice de Gravidade de Doença , Inquéritos e Questionários , Adulto , Parto Obstétrico/métodos , Extração Obstétrica/efeitos adversos , Feminino , Humanos , Manometria , Idade Materna , Gravidez , Estudos Retrospectivos , Avaliação de Sintomas , Índices de Gravidade do Trauma
2.
Pharmacogenomics J ; 18(3): 436-443, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29205207

RESUMO

Translation of drug candidates into clinical settings requires demonstration of preclinical efficacy and formal toxicology analysis for filling an Investigational New Drug (IND) application with the US Food and Drug Administration (FDA). Here, we investigate the membrane-associated glucose response protein 78 (GRP78) as a therapeutic target in leukemia and lymphoma. We evaluated the efficacy of the GRP78-targeted proapoptotic drug bone metastasis targeting peptidomimetic 78 (BMTP-78), a member of the D(KLAKLAK)2-containing class of agents. BMTP-78 was validated in cells from patients with acute myeloid leukemia and in a panel of human leukemia and lymphoma cell lines, where it induced dose-dependent cytotoxicity in all samples tested. Based on the in vitro efficacy of BMTP-78, we performed formal good laboratory practice toxicology studies in both rodents (mice and rats) and nonhuman primates (cynomolgus and rhesus monkeys). These analyses represent required steps towards an IND application of BMTP-78 for theranostic first-in-human clinical trials.


Assuntos
Avaliação Pré-Clínica de Medicamentos , Proteínas de Choque Térmico/genética , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Peptidomiméticos/administração & dosagem , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/antagonistas & inibidores , Humanos , Leucemia/patologia , Linfoma/patologia , Macaca fascicularis , Macaca mulatta , Camundongos , Terapia de Alvo Molecular , Peptidomiméticos/efeitos adversos , Primatas , Ratos , Estados Unidos , United States Food and Drug Administration
3.
Mucosal Immunol ; 9(2): 336-51, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26174764

RESUMO

A crosstalk between commensals, gut immune cells, and colonic epithelia is required for a proper function of intestinal mucosal barrier. Here we investigated the importance of two distinct intestinal dendritic cell (DC) subsets in controlling intestinal inflammation. We show that Clec9A-diphtheria toxin receptor (DTR) mice after depletion of CD103(+)CD11b(-) DCs developed severe, low-dose dextran sodium sulfate (DSS)-induced colitis, whereas the lack of CD103(+)CD11b(+) DCs in Clec4a4-DTR mice did not exacerbate intestinal inflammation. The CD103(+)CD11b(-) DC subset has gained a functional specialization that able them to repress inflammation via several epithelial interferon-γ (IFN-γ)-induced proteins. Among others, we identified that epithelial IDO1 and interleukin-18-binding protein (IL-18bp) were strongly modulated by CD103(+)CD11b(-) DCs. Through its preferential property to express IL-12 and IL-15, this particular DC subset can induce lymphocytes in colonic lamina propria and in epithelia to secrete IFN-γ that then can trigger a reversible early anti-inflammatory response in intestinal epithelial cells.


Assuntos
Antígenos CD/imunologia , Antígeno CD11b/imunologia , Colite/imunologia , Células Dendríticas/imunologia , Resistência à Doença/imunologia , Cadeias alfa de Integrinas/imunologia , Interferon gama/imunologia , Animais , Antígenos CD/genética , Antígeno CD11b/genética , Colite/induzido quimicamente , Colite/genética , Colite/patologia , Colo/imunologia , Colo/patologia , Células Dendríticas/patologia , Sulfato de Dextrana , Células Epiteliais/imunologia , Células Epiteliais/patologia , Feminino , Regulação da Expressão Gênica , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/imunologia , Cadeias alfa de Integrinas/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interferon gama/genética , Interleucina-12/genética , Interleucina-12/imunologia , Interleucina-15/genética , Interleucina-15/imunologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/patologia , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Transdução de Sinais
4.
Scand J Surg ; 99(3): 132-6, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21044929

RESUMO

BACKGROUND AND AIMS: minilaparotomy (MC) and laparoscopic cholecystectomy (LC) are commonly applied surgical techniques in the management of symptomatic gallstone disease. Both techniques are used in day surgery patients, but to our knowledge MC and LC have not been compared in randomised trials as day surgery procedures. MATERIAL AND METHODS: in this randomised parallel group clinical trial we compared the suc-cess rate of day surgery of MC with that of LC in 60 consecutive patients with non-complicated symptomatic gallstones presented for elective surgery at the Kuusankoski District Hospital (n = 38) and the Kuopio University Hospital (n = 22). Twenty nine patients underwent MC and 31 LC. The patients' outcome was recorded up to four weeks after the operation. RESULTS: the success rate as a day surgery for MC was 66% (19/29) and that for LC 55% (17/31) with no difference between the two groups. Chronic cholecystitis, postoperative nausea and vomiting were significant variables associated with failure in day surgery. There was no difference between the two groups in operation time, perioperative bleeding, conversion to conventional open cholecystectomy (one with MC and three with LC), length of hospital stay or sick leave. Three patients developed superficial infection (two with MC and one with LC). One patient with conversion in the LC-group developed a common bile duct stricture and was readmitted at the 10th postoperative day. DISCUSSION: both MC and LC are feasible surgical techniques for day surgery. However, appropriate prevention and prompt management of established postoperative nausea and vomit-ing and careful patient selection are important aspects for success of short-stay approach. If there is a sign of chronic cholecystitis preoperatively, it might be considered as a contraindication for day surgery.


Assuntos
Colecistectomia Laparoscópica , Colecistectomia/métodos , Colelitíase/cirurgia , Procedimentos Cirúrgicos Ambulatórios/métodos , Colecistite/etiologia , Colecistite/cirurgia , Colelitíase/complicações , Contraindicações , Humanos , Laparotomia/métodos , Tempo de Internação , Estudos Prospectivos
5.
Cochrane Database Syst Rev ; (2): CD000963, 2007 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-17636646

RESUMO

BACKGROUND: Chronic low back pain is, in many countries, the main cause of long term disability in middle age. Patients with chronic low back pain are often referred for multidisciplinary treatment. Previous published systematic reviews on this topic included no randomised controlled trials and pooled together controlled and non-controlled studies. OBJECTIVES: To assess the effect of multidisciplinary bio-psycho-social rehabilitation on pain, function, employment, quality of life and global assessment outcomes in subjects with chronic disabling low back pain. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsychLIT, CINAHL, Health STAR, and The Cochrane Library from the beginning of the database to June 1998 using the comprehensive search strategy recommended by the Back Review Group of the Cochrane Collaboration. INTERVENTION specific key words for this review were: patient care team, patient care management, multidisciplinary, interdisciplinary, multiprofessional, multimodal, pain clinic and functional restoration. We also reviewed reference lists and consulted the editors of the Back Review Group of the Cochrane Collaboration. DESIGN: randomised controlled trials comparing multidisciplinary bio-psycho-social rehabilitation with a non-multidisciplinary control intervention. POPULATION: Adults with disabling low back pain of more than three months in duration. INTERVENTION: Patients had to be assessed and treated by qualified professionals according to a plan that addresses physical and at least one of psychological, or social/occupational dimensions. OUTCOMES: Only trials which reported treatment effect in at least one of pain, function, employment status, quality of life or global improvement.Exclusion: Pure educational interventions (back schools) and pure physical interventions were excluded. DATA COLLECTION AND ANALYSIS: Selection, data extraction and quality grading of studies was done by two independent authors using pre-tested data forms. Study quality was assessed according to the scheme recommended by the Back Review Group of the Cochrane Collaboration. Trials with internal validity scores of five or more in a ten point scale were considered high quality. Discrepancies between authors were resolved by consensus or by a third author. Given the marked heterogeneity in study settings, interventions and control groups we decided not to pool trial results in a meta-analysis. Instead, we summarized findings by strength of evidence and nature of intervention and control treatments. The evidence was judged to be strong when multiple high quality trials produced generally consistent findings. It was judged to be moderate when multiple low quality or one high quality and one or more low quality trials produced generally consistent findings. Evidence was considered to be limited when only one randomised trial existed or if findings of existing trials were inconsistent. MAIN RESULTS: Ten trials (12 randomised comparisons) were included. They randomised a total of 1964 patients with chronic low back pain. There was strong evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved function when compared with inpatient or outpatient non-multidisciplinary treatments. There was moderate evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved pain when compared with outpatient non-multidisciplinary rehabilitation or usual care. There was contradictory evidence regarding vocational outcomes of intensive multidisciplinary bio-psycho-social intervention. Some trials reported improvements in work readiness, but others showed no significant reduction in sickness leaves. Less intensive outpatient psycho-physical treatments did not improve pain, function or vocational outcomes when compared with non-multidisciplinary outpatient therapy or usual care. Few trials reported effects on quality of life or global assessments. AUTHORS' CONCLUSIONS: The reviewed trials provide evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improves pain and function. Less intensive interventions did not show improvements in clinically relevant outcomes.


Assuntos
Dor nas Costas/reabilitação , Dor nas Costas/psicologia , Doença Crônica , Humanos , Terapia Ocupacional/métodos , Psicoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Apoio Social
6.
Cochrane Database Syst Rev ; (2): CD002193, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12804427

RESUMO

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs are widely applied for chronic low back pain patients. The biopsychosocial approach can also prevent chronicity, by providing rehabilitation for patients who still have pain past the initial acute phase. Nevertheless, multidisciplinary treatment programmes are often laborious and long processes and require good collaboration between the patient, the rehabilitation team and the work place. By using workplace visits and developing close relationships with occupational health care providers, one might expect patients' working ability to improve. OBJECTIVES: The objective of this systematic review was to determine the effectiveness of multidisciplinary rehabilitation for subacute low back pain among working age adults. SEARCH STRATEGY: The reviewed studies for this review were electronically identified from MEDLINE, EMBASE, PsycLIT, CENTRAL, Medic, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for the broader area of musculoskeletal disorders. Trials on subacute low back pain were separated afterwards. The literature search was last updated in November 2002 in EMBASE and MEDLINE. SELECTION CRITERIA: From all references identified in our original search, we selected randomised controlled trials (RCTs) and non-randomised controlled clinical trials (CCTs). Trials had to assess the effectiveness of multidisciplinary rehabilitation for working age patients suffering from subacute low back pain (more than four weeks but less than three months). The rehabilitation program was required to be multidisciplinary, i.e., it had to consist of a physician's consultation plus either a psychological, social or vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS: Four reviewers blinded to journal and author selected trials that met the specified inclusion criteria. Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies for actual clinical use. Two other reviewers blinded to journal and author extracted the data and assessed the main results and the methodological quality of the studies, using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of multidisciplinary rehabilitation. MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we found only two relevant studies that satisfied our criteria on subacute low back pain. No more studies were found during the updates. Both studies were considered to be methodologically low quality RCTs. The clinical relevance of included studies was sufficient. There was moderate scientific evidence showing that multidisciplinary rehabilitation, which includes a workplace visit or more comprehensive occupational health care intervention, helps patients to return to work faster, results in fewer sick leaves and alleviates subjective disability. REVIEWER'S CONCLUSIONS: We conclude that there is moderate evidence of positive effectiveness of multidisciplinary rehabilitation for subacute low back pain and that a workplace visit increases the effectiveness. But because this evidence is based on trials that had some methodological shortcomings, and several expensive multidisciplinary rehabilitation programmes are commonly used for uncomplicated/non-specific subacute low back problems, there is an obvious need for high quality trials in this field.


Assuntos
Dor Lombar/reabilitação , Doença Aguda , Adulto , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Dor Lombar/psicologia , Clínicas de Dor , Recuperação de Função Fisiológica , Local de Trabalho
7.
Cochrane Database Syst Rev ; (2): CD002194, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12804428

RESUMO

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs for neck and shoulder pain require substantial staff and financial resources. Despite questionable scientific evidence of their effectiveness, they are widely used. Neck and shoulder complaints are common among working age adults and they are often associated with physical work load and stress. Pain in the neck and shoulder area cause biopsychosocial difficulties for the patient, especially if disability due to pain is prolonged. To help patients with biopsychosocial problems, or to prevent their development, multidisciplinary biopsychosocial programs are used for rehabilitation for patients with neck and shoulder pain. Nevertheless, multidisciplinary treatment programmes are often laborious and rather long processes and require good collaboration between the patient, the rehabilitation team and the work place. OBJECTIVES: The objective of this systematic review was to determine the effectiveness of multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among working age adults. SEARCH STRATEGY: The reviewed studies for this review were electronically identified from MEDLINE, EMBASE, PsycLIT, CENTRAL, Medic, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for more broad area of musculoskeletal disorders. Trials on neck and shoulder pain were separated afterwards. The literature search was updated in November 2002 by electronically searching MEDLINE and EMBASE. SELECTION CRITERIA: From all references identified in our original search, we selected randomized controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs). Trials had to assess the effectiveness of biopsychosocial rehabilitation for working age adults suffering from neck and shoulder pain. The rehabilitation program was required to be multidisciplinary, i.e., it had to consist of a physician's consultation plus either a psychological, social or vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS: Four reviewers blinded to journal and author selected the trials that met the specified inclusion criteria. Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies for actual clinical use. Two other reviewers blinded to journal and author extracted the data and assessed the main results and the methodological quality of the studies, using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation. MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we found only two relevant studies that satisfied our criteria. No more studies were found for this update. One of the studies was considered to be a methodologically low quality RCT and the other one was a methodologically low quality CCT. The clinical relevance of included studies was satisfactory. There was limited scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain. REVIEWER'S CONCLUSIONS: We conclude that there appears to be little scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation compared with other rehabilitation facilities for neck and shoulder pain. Multidisciplinary rehabilitation is a commonly used intervention for chronic neck and shoulder complaints, therefore we see an urgent need for high quality trials in this field.


Assuntos
Cervicalgia/reabilitação , Dor de Ombro/reabilitação , Adulto , Terapia Combinada , Humanos , Pessoa de Meia-Idade , Cervicalgia/psicologia , Clínicas de Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor de Ombro/psicologia
8.
Cochrane Database Syst Rev ; (1): CD000963, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-11869581

RESUMO

BACKGROUND: Chronic low back pain is, in many countries, the main cause of long term disability in middle age. Patients with chronic low back pain are often referred for multidisciplinary treatment. Previous published systematic reviews on this topic included no randomised controlled trials and pooled together controlled and non-controlled studies. OBJECTIVES: To assess the effect of multidisciplinary bio-psycho-social rehabilitation on pain, function, employment, quality of life and global assessment outcomes in subjects with chronic disabling low back pain. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsychLIT, CINAHL, Health STAR, and The Cochrane Library from the beginning of the database to June 1998 using the comprehensive search strategy recommended by the Back Review Group of the Cochrane Collaboration. INTERVENTION specific key words for this review were: patient care team, patient care management, multidisciplinary, interdisciplinary, multiprofessional, multimodal, pain clinic and functional restoration. We also reviewed reference lists and consulted the editors of the Back Review Group of the Cochrane Collaboration. DESIGN: randomised controlled trials comparing multidisciplinary bio-psycho-social rehabilitation with a non-multidisciplinary control intervention. POPULATION: Adults with disabling low back pain of more than three months in duration. INTERVENTION: Patients had to be assessed and treated by qualified professionals according to a plan that addresses physical and at least one of psychological, or social/occupational dimensions. OUTCOMES: Only trials which reported treatment effect in at least one of pain, function, employment status, quality of life or global improvement. Exclusion: Pure educational interventions (back schools) and pure physical interventions were excluded. DATA COLLECTION AND ANALYSIS: Selection, data extraction and quality grading of studies was done by two independent reviewers using pre-tested data forms. Study quality was assessed according to the scheme recommended by the Back Review Group of the Cochrane Collaboration. Trials with internal validity scores of five or more in a ten point scale were considered high quality. Discrepancies between reviewers were resolved by consensus or by a third reviewer. Given the marked heterogeneity in study settings, interventions and control groups we decided not to pool trial results in a meta-analysis. Instead, we summarized findings by strength of evidence and nature of intervention and control treatments. The evidence was judged to be strong when multiple high quality trials produced generally consistent findings. It was judged to be moderate when multiple low quality or one high quality and one or more low quality trials produced generally consistent findings. Evidence was considered to be limited when only one randomised trial existed or if findings of existing trials were inconsistent. MAIN RESULTS: Ten trials (12 randomised comparisons) were included. They randomised a total of 1964 patients with chronic low back pain. There was strong evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved function when compared with inpatient or outpatient non-multidisciplinary treatments. There was moderate evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improved pain when compared with outpatient non-multidisciplinary rehabilitation or usual care. There was contradictory evidence regarding vocational outcomes of intensive multidisciplinary bio-psycho-social intervention. Some trials reported improvements in work readiness, but others showed no significant reduction in sickness leaves. Less intensive outpatient psycho-physical treatments did not improve pain, function or vocational outcomes when compared with non-multidisciplinary outpatient therapy or usual care. Few trials reported effects on quality of life or global assessments. REVIEWER'S CONCLUSIONS: The reviewed trials provide evidence that intensive multidisciplinary bio-psycho-social rehabilitation with a functional restoration approach improves pain and function. Less intensive interventions did not show improvements in clinically relevant outcomes.


Assuntos
Dor nas Costas/reabilitação , Dor nas Costas/psicologia , Doença Crônica , Humanos , Terapia Ocupacional/métodos , Psicoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Apoio Social
9.
J Biol Chem ; 276(52): 49125-32, 2001 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-11592972

RESUMO

To address the molecular mechanism of T cell receptor (TCR) signaling, we have formulated a model for T cell activation, termed the 2D-affinity model, in which the density of TCR on the T cell surface, the density of ligand on the presenting surface, and their corresponding two-dimensional affinity determine the level of T cell activation. When fitted to T cell responses against purified ligands immobilized on plastic surfaces, the 2D-affinity model adequately simulated changes in cellular activation as a result of varying ligand affinity and ligand density. These observations further demonstrated the importance of receptor cross-linking density in determining TCR signaling. Moreover, it was found that the functional two-dimensional affinity of TCR ligands was affected by the chemical composition of the ligand-presenting surface. This makes it possible that cell-bound TCR ligands, despite their low affinity in solution, are of optimal two-dimensional affinity thereby allowing effective TCR binding under physiological conditions, i.e. at low ligand densities in cellular interfaces.


Assuntos
Ativação Linfocitária , Modelos Imunológicos , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais/fisiologia , Linfócitos T/imunologia , Anticorpos/imunologia , Anticorpos/metabolismo , Genes Reporter , Ligantes , Matemática , Ligação Proteica , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/metabolismo , Superantígenos/imunologia , Superantígenos/metabolismo
10.
BMJ ; 322(7301): 1511-6, 2001 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-11420271

RESUMO

OBJECTIVE: To assess the effect of multidisciplinary biopsychosocial rehabilitation on clinically relevant outcomes in patients with chronic low back pain. DESIGN: Systematic literature review of randomised controlled trials. PARTICIPANTS: A total of 1964 patients with disabling low back pain for more than three months. MAIN OUTCOME MEASURES: Pain, function, employment, quality of life, and global assessments. RESULTS: Ten trials reported on a total of 12 randomised comparisons of multidisciplinary treatment and a control condition. There was strong evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration improves function when compared with inpatient or outpatient non-multidisciplinary treatments. There was moderate evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration reduces pain when compared with outpatient non-multidisciplinary rehabilitation or usual care. There was contradictory evidence regarding vocational outcomes of intensive multidisciplinary biopsychosocial intervention. Some trials reported improvements in work readiness, but others showed no significant reduction in sickness leaves. Less intensive outpatient psychophysical treatments did not improve pain, function, or vocational outcomes when compared with non-multidisciplinary outpatient therapy or usual care. Few trials reported effects on quality of life or global assessments. CONCLUSIONS: The reviewed trials provide evidence that intensive multidisciplinary biopsychosocial rehabilitation with functional restoration reduces pain and improves function in patients with chronic low back pain. Less intensive interventions did not show improvements in clinically relevant outcomes.


Assuntos
Dor Lombar/reabilitação , Resultado do Tratamento , Doença Crônica , Terapia Combinada , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
J Biol Chem ; 276(36): 33452-7, 2001 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-11397806

RESUMO

Similar to native peptide/MHC ligands, bacterial superantigens have been found to bind with low affinity to the T cell receptor (TCR). It has been hypothesized that low ligand affinity is required to allow optimal TCR signaling. To test this, we generated variants of Staphylococcus enterotoxin C3 (SEC3) with up to a 150-fold increase in TCR affinity. By stimulating T cells with SEC3 molecules immobilized onto plastic surfaces, we demonstrate that increasing the affinity of the SEC3/TCR interaction caused a proportional increase in the ability of SEC3 to activate T cells. Thus, the potency of the SEC3 variants correlated with enhanced binding without any optimum in the binding range covered by native TCR ligands. Comparable studies using anti-TCR antibodies of known affinity confirmed these observations. By comparing the biological potency of the two sets of ligands, we found a significant correlation between ligand affinity and ligand potency indicating that it is the density of receptor-ligand complexes in the T cell contact area that determines TCR signaling strength.


Assuntos
Antígenos de Bactérias/metabolismo , Enterotoxinas/metabolismo , Ligantes , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/fisiologia , Animais , Linhagem Celular , Relação Dose-Resposta a Droga , Drosophila , Ensaio de Imunoadsorção Enzimática , Humanos , Hibridomas/metabolismo , Cinética , Camundongos , Camundongos Transgênicos , Modelos Moleculares , Ligação Proteica , Estrutura Terciária de Proteína , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Fatores de Tempo
12.
J Immunol ; 166(12): 7178-82, 2001 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-11390465

RESUMO

We have been able to identify the cell subset derived from Langerhans cells in the total dendritic cell population of the peripheral lymph node and hence to follow their trafficking under normal physiological conditions as well as upon skin irritation. As expected, the rapid mobilization of Langerhans cells triggered by inflammatory signals into the draining lymph node correlated with an up-regulation of costimulatory molecules and with an enhanced immunostimulatory capacity. Surprisingly, however, these cells, instead of shutting down, maintain the capacity to capture and process protein Ags during the couple of days they stay alive in stark contrast to in vitro-matured dendritic cells.


Assuntos
Apresentação de Antígeno , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Lectinas Tipo C , Lectinas de Ligação a Manose , Animais , Carbocianinas/metabolismo , Diferenciação Celular/imunologia , Movimento Celular/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Endocitose/imunologia , Epitopos de Linfócito T/metabolismo , Corantes Fluorescentes/metabolismo , Irritantes/farmacologia , Células de Langerhans/citologia , Linfonodos/citologia , Linfonodos/imunologia , Receptor de Manose , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Ovalbumina/imunologia , Ovalbumina/metabolismo , Receptores de Superfície Celular/fisiologia , Pele/citologia , Pele/efeitos dos fármacos , Pele/imunologia , Solubilidade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
13.
Eur J Immunol ; 31(4): 1141-9, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11298339

RESUMO

Studies on thymic T cell development have usually concentrated on cell surface molecules. However, intracellular proteins expressed only in thymocytes have never been described. Here we report the discovery of a novel thymocyte-specific protein, named TARPP, which represents a high molecular mass ( approximately 100 kDa) variant of the previously identified protein ARPP-21 ( approximately 21 kDa). TARPP is a cytosolic protein that is expressed at high levels in immature thymocytes. It appears concomitant with the commitment to T cell lineage, and its expression is switched off as a consequence of TCR engagement during positive selection. Such an expression pattern, correlating with the rearrangement of the TCR genes and thymocyte education, suggests a role for TARPP during this important phase of thymocyte development.


Assuntos
Diferenciação Celular , Rearranjo Gênico do Linfócito T/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Timo/citologia , Timo/metabolismo , Envelhecimento/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos , Sequência de Bases , Complexo CD3/metabolismo , Linhagem da Célula , Células Cultivadas , Clonagem Molecular , Regulação para Baixo , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Peso Molecular , Fosfoproteínas/química , Proteína Fosfatase 1 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Timo/embriologia , Timo/imunologia
14.
Spine (Phila Pa 1976) ; 26(3): 262-9, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11224862

RESUMO

STUDY DESIGN: A systematic review of randomized controlled trials was performed. OBJECTIVE: To evaluate the effectiveness of multidisciplinary biopsychosocial rehabilitation for subacute low back pain among working-age adults. SUMMARY OF BACKGROUND DATA: Multidisciplinary biopsychosocial rehabilitation programs are widely applied for patients with chronic low back pain. The multidisciplinary biopsychosocial approach for prolonged low back pain could be considered to prevent chronicity. Work site visits and a close relationship with occupational health care might produce results in terms of patients working ability. METHODS: Reviewed randomized controlled trials as well as controlled trials were identified from electronic bibliographic databases, reference checking, and consultation with experts in the rehabilitation field. Four blinded reviewers selected the trials. Two rehabilitation specialists evaluated the clinical relevance. Two other blinded reviewers extracted the data and assessed the main results along with the methodologic quality of the studies. A qualitative analysis was performed to evaluate the level evidence. RESULTS: Of 1808 references, only 2 relevant studies were included. Both were considered to be methodologically low-quality randomized controlled trials. The clinical relevance of the studies was sufficient. The level of scientific evidence was moderate, showing that multidisciplinary rehabilitation involving work site visit or more comprehensive occupational health care intervention helps patients return to work faster, makes sick leaves less, and alleviates subjective disability. CONCLUSIONS: There is moderate evidence showing that multidisciplinary rehabilitation for subacute low back pain is effective, and that work site visit increases the effectiveness, but because the analyzed studies had some methodologic shortcomings, an obvious need still exists for high-quality trials in this field.


Assuntos
Dor Lombar/psicologia , Dor Lombar/reabilitação , Clínicas de Dor , Apoio Social , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
15.
Spine (Phila Pa 1976) ; 26(2): 174-81, 2001 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-11154538

RESUMO

STUDY DESIGN: A systematic review of randomized controlled trials. OBJECTIVES: To evaluate the effectiveness of multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain among working age adults. SUMMARY OF BACKGROUND DATA: Multidisciplinary biopsychosocial rehabilitation programs for neck and shoulder pain require substantial staff and financial resources. They are widely used, despite questionable evidence of their effectiveness. METHODS: The reviewed randomized controlled and controlled trials appraising the effectiveness of biopsychosocial rehabilitation for working age patients with neck and shoulder pain were identified by searching electronic bibliographic databases, checking references, and consulting experts in the rehabilitation field. Four blinded reviewers selected the trials. Two specialists on rehabilitation evaluated the clinical relevance. Two other blinded reviewers extracted the data and assessed the main results and the methodologic quality of the studies. A qualitative analysis was performed to evaluate the level of scientific evidence. RESULTS: After 1808 abstracts and the references of 65 reviews were screened, only two relevant studies were found that satisfied the criteria. One of these was considered a methodologically low-quality randomized controlled trial, and the other was a methodologically low-quality controlled clinical trial. The clinical relevance of included studies was satisfactory. The level of scientific evidence for the effectiveness of multidisciplinary biopsychosocial rehabilitation for neck and shoulder pain was limited. CONCLUSIONS: There appears to be little scientific evidence for the effectiveness on neck and shoulder pain of multidisciplinary biopsychosocial rehabilitation compared with other rehabilitation methods. There is an urgent need for high-quality trials in this field.


Assuntos
Doenças Musculoesqueléticas/reabilitação , Cervicalgia/reabilitação , Dor de Ombro/reabilitação , Adulto , Fatores Etários , Ensaios Clínicos como Assunto , Humanos , Doenças Musculoesqueléticas/psicologia , Cervicalgia/psicologia , Clínicas de Dor , Psicologia , Reprodutibilidade dos Testes , Dor de Ombro/psicologia , Resultado do Tratamento
16.
Scand J Work Environ Health ; 26(5): 373-81, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11103835

RESUMO

The objective of this study was to determine the effectiveness of biopsychosocial rehabilitation for upper-limb repetitive-strain injuries among working-age adults. Studies were identified from electronic bibliographic databases, reference checks, and consultations with experts in rehabilitation. Four blinded reviewers selected randomized controlled and controlled trials. Two experts evaluated the clinical relevance of the findings. Two other reviewers extracted the data and assessed the main results and the methodological quality of the studies. Finally, a qualitative analysis was performed. Only 2 studies satisfied the criteria. They were both considered to be low-quality trials. The clinical relevance of the included studies was also unsatisfactory. The level of scientific evidence was limited, showing that hypnosis as a supplement to comprehensive treatment can decrease the pain intensity of acute repetitive-strain injury in short follow-ups. There appears to be little scientific evidence for the effectiveness of biopsychosocial rehabilitation with respect to repetitive-strain injuries.


Assuntos
Transtornos Traumáticos Cumulativos/reabilitação , Doenças Profissionais/reabilitação , Adolescente , Adulto , Idoso , Braço , Síndrome do Túnel Carpal/psicologia , Síndrome do Túnel Carpal/reabilitação , Ensaios Clínicos como Assunto , Transtornos Traumáticos Cumulativos/psicologia , Feminino , Seguimentos , Humanos , Hipnose , MEDLINE , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/psicologia , Equipe de Assistência ao Paciente , Pacientes Desistentes do Tratamento , Modalidades de Fisioterapia , Qualidade da Assistência à Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Ajustamento Social , Fatores de Tempo , Resultado do Tratamento
17.
J Immunol ; 165(9): 4910-6, 2000 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-11046016

RESUMO

Dendritic cells (DCs) exhibit considerable heterogeneity in their anatomical location, surface phenotype, and functional properties. In this study, we demonstrate that peripheral lymph nodes contain at least four major, functionally separable, and independently derived, DC subsets, which can be clearly demarcated by their CD11c, CD40, and CD8 expression pattern. Surprisingly, all DCs derived directly from the bone marrow, the myeloid- and the lymphoid-related subsets, turned over fast with t(1/2) of a couple of days. In contrast, DCs exported from the skin, both dermal and epidermal, accumulated 3- to 4-fold slower, turnover that is dramatically increased by cutaneous inflammation.


Assuntos
Movimento Celular/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Linfonodos/citologia , Linfonodos/imunologia , Administração Cutânea , Animais , Linhagem da Célula/imunologia , Separação Celular , Sobrevivência Celular/imunologia , Células Dendríticas/classificação , Imunofenotipagem , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Especificidade de Órgãos/imunologia , Peptídeos/administração & dosagem , Peptídeos/imunologia , Pele/efeitos dos fármacos , Pele/imunologia , Testes Cutâneos , Linfócitos T/imunologia
18.
Life Sci ; 67(3): 283-90, 2000 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-10983872

RESUMO

The effects of three-month dietary xylitol supplementation on the amounts and hexose contents of acid-soluble collagen as well as on the amounts and fluorescence of collagenase-soluble collagen were studied in healthy and streptozotocin-diabetic male rats. Collagen was extracted from skin samples. In the healthy rats, supplementation with xylitol (10%) increased the hydroxyproline content of the acid-soluble fraction and skin thickness. In diabetic rats receiving and not receiving xylitol, the acid-soluble collagen fraction was markedly lower than in healthy rats. However, its amount was significantly elevated when xylitol had been added to the diet. Supplementation with xylitol caused no changes in the amounts of collagenase-soluble fraction in either healthy or diabetic rats. Supplementation with xylitol (10%) significantly decreased the hexose content of acid-soluble collagen and the fluorescence of the collagenase-soluble fraction in both healthy and diabetic rats. The results indicate that dietary xylitol affects collagen synthesis and collagen glycosylation.


Assuntos
Colágeno/metabolismo , Diabetes Mellitus Experimental/metabolismo , Xilitol/farmacologia , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Suplementos Nutricionais , Glicosilação/efeitos dos fármacos , Hidroxiprolina/metabolismo , Insulina/sangue , Masculino , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/metabolismo , Xilitol/administração & dosagem
19.
J Clin Periodontol ; 27(8): 567-71, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10959782

RESUMO

UNLABELLED: AIM, BACKGROUND: The aim of this study was to assess the degree of marginal alveolar bone loss in a group of young subjects with type 1 diabetes mellitus (DM) (n=35, age range 24-36 years) and age-matched non-diabetic control subjects (n=10). METHOD: The diabetic group was divided into 3 subgroups (D1, D2, D3) according to the severity of the diabetic state. The level of alveolar bone was measured on panoramic radiographs of maxillary and mandibular molars as the % of the distance between the cemento-enamel junction (CEJ) and the bone crest along the total length of the root. All mesial and distal sites with a distance of > 15% (BL>15%) were picked, and calculations were performed using the individual %s of sites with BL> 15%. RESULTS: Based on the present findings, we conclude that type 1 DM has a modifying effect on marginal loss of alveolar bone. A clear trend towards increased marginal bone loss was seen in the subjects with complicated DM (D3). The subjects with good metabolic control and no complications of DM (D1) are no more susceptible to marginal bone loss than non-diabetic controls of the same age. CONCLUSIONS: The present findings confirm our previous results on increased loss of periodontal support in subjects with complicated DM already at an early age.


Assuntos
Perda do Osso Alveolar/etiologia , Diabetes Mellitus Tipo 1/complicações , Adulto , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/metabolismo , Análise de Variância , Estudos de Casos e Controles , Hemoglobinas Glicadas/análise , Humanos , Radiografia , Estatísticas não Paramétricas
20.
Cochrane Database Syst Rev ; (3): CD002193, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10908528

RESUMO

BACKGROUND: Multidisciplinary biopsychosocial rehabilitation programs are widely applied for chronic low back pain patients. The biopsychosocial approach for low back pain could also be considered to prevent chronicity by carrying out the rehabilitation if the acute pain is prolonged. Nevertheless multidisciplinary treatment programmes are often laborious and long processes and require good collaboration between the patient, the rehabilitation team and the work place. By workplace visits and close relationship with occupational health care one might expect results in terms of patients working ability. OBJECTIVES: The objective of this systematic review was to determine the effectiveness of multidisciplinary rehabilitation for subacute low back pain among working age adults. SEARCH STRATEGY: The reviewed studies for this structured Cochrane review were identified from electronic bibliographic databases, the Science Citation Index, reference checking and consulting experts in the rehabilitation field. The original search was planned and performed for more broad area of musculoskeletal disorders. Trials on subacute low back pain were separated afterwards. SELECTION CRITERIA: From all references found in our original search we selected randomized controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs). Trials had to assess the effectiveness of multidisciplinary rehabilitation for working age patients suffering from subacute low back pain (more than 4 weeks but less than 3 months). The rehabilitation program was required to be multidisciplinary, i.e.; it had to consist of a physician's consultation plus either a psychological, social or vocational intervention, or a combination of these. DATA COLLECTION AND ANALYSIS: Four blinded reviewers selected the randomized controlled trials and controlled trials that met the specified inclusion criteria. Two experts in the field of rehabilitation evaluated the clinical relevance and applicability of the findings of the selected studies to actual clinical use. Two other blinded reviewers extracted the data and assessed the main results and the methodological quality of the studies using standardized forms. Finally, a qualitative analysis was performed to evaluate the level of scientific evidence for the effectiveness of multidisciplinary rehabilitation. MAIN RESULTS: After screening 1808 abstracts, and the references of 65 reviews, we found only 2 relevant studies that satisfied our criteria on subacute low back pain. They were both considered to be methodologically low quality randomized controlled trials. The clinical relevance of included studies was sufficient. The level of scientific evidence for the effectiveness of multidisciplinary rehabilitation was moderate on subacute low back pain showing that multidisciplinary rehabilitation which includes workplace visit or more comprehensive occupational health care intervention helps patients to return to work faster, makes sick leaves less and alleviates subjective disability. REVIEWER'S CONCLUSIONS: We conclude that there is moderate evidence of positive effectiveness of multidisciplinary rehabilitation for subacute low back pain and workplace visit increases the effectiveness. But because this evidence is based on the trials that had some methodological shortcomings and several expensive multidisciplinary rehabilitation programmes are commonly used for common subacute low back problems, there is an obvious need for high quality trials in this field.


Assuntos
Dor Lombar/reabilitação , Doença Aguda , Adulto , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Clínicas de Dor , Recuperação de Função Fisiológica
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