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1.
Pituitary ; 27(3): 294-302, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521837

RESUMO

PURPOSE: Acromegaly is a rare disease associated with chronic multisystem complications. New therapeutic strategies have emerged in the last decades, combining pituitary transsphenoidal surgery (TSS), radiotherapy or radiosurgery (RXT) and medical treatments. METHODS: This retrospective monocentric study focused on presentation, management and outcome of acromegaly patients diagnosed between 2000 and 2020, still followed up in 2020, with a minimum follow-up of 1 year, and comparison of the first vs. second decade of the study. RESULTS: 275 patients were included, 50 diagnosed before 2010 and 225 after 2010. 95% of them had normal IGF-1 levels (with or without treatment) at the last follow-up. Transsphenoidal surgery was more successful after 2010 (75% vs. 54%; p < 0.01), while tumor characteristics remained the same over time. The time from first treatment to biochemical control was shorter after 2010 than before (8 vs. 16 months; p = 0.03). Since 2010, RT was used less frequently (10% vs. 32%; p < 0.01) but more rapidly after surgery (26 vs. 53 months; p = 0.03). In patients requiring anti-secretory drugs after TSS, the time from first therapy to biochemical control was shorter after 2010 (16 vs. 29 months; p < 0.01). Tumor size, tumor invasiveness, baseline IGF-1 levels and Trouillas classification were identified as predictors of remission. CONCLUSION: The vast majority of patients with acromegaly now have successful disease control with a multimodal approach. They reached biochemical control sooner in the most recent half of the study period. Future work should focus on those patients who are still uncontrolled and on the sequelae of the disease.


Assuntos
Acromegalia , Humanos , Acromegalia/terapia , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Fator de Crescimento Insulin-Like I/metabolismo , Radiocirurgia , Idoso , Terapia Combinada , Centros de Atenção Terciária , Resultado do Tratamento
3.
Indoor Air ; 19(1): 58-67, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19076249

RESUMO

UNLABELLED: We used data from 4345 adult US residents who were part of a 2004 national random mail survey to investigate associations between dampness and air-conditioning (AC) in homes and offices, and health outcomes, sick leave due to respiratory symptoms and medical visits during the past 12 months. We identified from this group 1396 office workers employed in professional, executive, administrative, managerial or administrative support occupations. Office workers reporting home dampness had an elevated prevalence of nasal symptoms [prevalence ratio (PR) = 1.4, P = 0.01] and constitutional symptoms (PR = 1.3, P = 0.01) in the previous year. Office workers reporting workplace dampness had an elevated prevalence of sick leave attributed to respiratory symptoms (PR = 1.3, P = 0.04) in the previous year. Office workers with home AC were more likely to have visited a medical specialist in the previous year (PR = 1.3, P = 0.02). We did not find any statistically significant associations between workplace AC and any of the health outcomes. We estimated an annual cost of US$1.4 billion for excess respiratory-related sick leave among office workers with workplace dampness. Our study strengthens the evidence of a relationship between dampness and health effects, and highlights the resulting economic impact. PRACTICAL IMPLICATIONS: This study adds to the literature on respiratory morbidity associated with home and office exposures to mold and dampness. Public health response to lessen these exposures will improve the health and well-being of residents and workers as well as diminish the economic burden of lost work time and medical costs.


Assuntos
Ar Condicionado/efeitos adversos , Poluição do Ar em Ambientes Fechados/efeitos adversos , Umidade/efeitos adversos , Visita a Consultório Médico/estatística & dados numéricos , Doenças Respiratórias/etiologia , Adolescente , Adulto , Idoso , Poluição do Ar em Ambientes Fechados/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Doenças Respiratórias/economia , Doenças Respiratórias/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
4.
Immunol Allergy Clin North Am ; 28(3): 485-505, vii, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18572103

RESUMO

This article presents epidemiologic findings pertinent to asthma and asthma-like symptoms in relation to exposure to dampness/mold in homes, schools, and workplaces. With regard to specific agents found in damp indoor environments that may play a role in asthma, it concentrates on mold (used synonymously with fungi) and includes some findings on bacteria. The literature on asthma in relation to dust mite or cockroach allergens is not addressed.


Assuntos
Poluição do Ar em Ambientes Fechados/efeitos adversos , Asma/etiologia , Exposição Ambiental/efeitos adversos , Fungos , Umidade/efeitos adversos , Habitação , Humanos , Instituições Acadêmicas , Local de Trabalho
5.
J Am Vet Med Assoc ; 209(10): 1730-2, 1996 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-8921030

RESUMO

OBJECTIVE: To validate a new immunoradiometric assay for canine thyroid-stimulating hormone (cTSH) and to document changes in serum cTSH concentration during induction of hypothyroidism in dogs. ANIMALS: Six healthy adult male Beagles. PROCEDURE: Sensitivity, specificity, precision, and accuracy of the cTSH assay were evaluated in vitro. Hypothyroidism was induced in dogs by i.v. administration of sodium iodide I 131 solution. Subsequently, L-thyroxine was administered orally to normalize serum thyroxine concentrations. RESULTS: The cTSH assay appeared to be specific and was sufficiently sensitive to detect cTSH in the serum of these dogs prior to induction of hypothyroidism. There was a 35-fold increase in mean serum cTSH concentration following induction of hypothyroidism, and 35 days after initiation of thyroid replacement therapy, mean serum cTSH concentration was not significantly greater than mean baseline value. CLINICAL IMPLICATIONS: Assay of serum cTSH is likely to prove helpful in the differential diagnosis of primary, secondary, and tertiary hypothyroidism in dogs, and in monitoring response to thyroid hormone replacement treatment.


Assuntos
Doenças do Cão/sangue , Cães/sangue , Hipotireoidismo/veterinária , Tireotropina/sangue , Animais , Diagnóstico Diferencial , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Masculino , Radioimunoensaio/veterinária , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Tiroxina/sangue , Tiroxina/uso terapêutico
6.
Arthritis Rheum ; 33(7): 978-84, 1990 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2114876

RESUMO

Serum levels of IdGN2 (an idiotype enriched in nephritogenic antibodies), IdX (an idiotype not enriched in nephritogenic antibodies), IgG, and anti-DNA were measured in 23 Caucasian patients with lupus nephritis, in age- and sex-matched lupus patients without nephritis, and in similarly matched healthy individuals. Serum levels of IdGN2 were significantly higher in the patients with lupus nephritis than in those without, and they were higher in all lupus patients compared with the healthy control subjects. However, the same observations were true for serum levels of IdX. There were significant positive correlations between the serum levels of IgG, IdGN2, IdX, and anti-DNA. HLA typing at the DR and DQ loci was performed in 105 lupus patients of different races (Caucasian, black, and Asian/Polynesian/Filipino). Serum levels of IdGN2 in 83 of these individuals did not correlate with any of the HLA class II haplotypes currently known to predispose to lupus nephritis. We conclude that the high serum levels of IdGN2, which are characteristic of some patients with lupus nephritis, may often result from polyclonal B cell activation rather than from idiotype-specific upregulation associated with one or more of the class II genes that predispose to nephritis in this disease.


Assuntos
Idiótipos de Imunoglobulinas/análise , Lúpus Eritematoso Sistêmico/imunologia , Genes MHC da Classe II , Antígenos HLA/genética , Humanos , Nefrite Lúpica/genética
7.
J Clin Invest ; 85(2): 530-40, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2129537

RESUMO

We have studied several monoclonal anti-double-stranded (ds) DNA antibodies for their ability to accelerate lupus nephritis in young NZB X NZW F1 female mice and to induce it in BALB/c mice. Two identified as pathogens in both strains have characteristics previously associated with nephritogenicity: expression of IgG2a isotype and IdGN2 idiotype. Both pathogenic antibodies used the combination of genes from the VHJ558 and VK9 subfamilies. Two weak pathogens failed to accelerate nephritis in young BW mice, but induced lupus nephritis in BALB/c mice. They both express IdGN2; one is cationic and an IgG3, the other is an IgG2a. Additional MAbs (some IgG2a, one IdGN2-positive) did not accelerate or induce nephritis. We have cloned and sequenced the variable regions of the immunoglobulin genes of one pathogenic autoantibody. No unique V, D, or J gene segments and no evidence of unusual mechanisms in generating diversity were used to construct this antibody. These data argue against use of unique abnormal Ig genes by systemic lupus erythematosus individuals to construct pathogenic autoantibody subsets. Instead, the major abnormality may be immunoregulatory.


Assuntos
Anticorpos Antinucleares/genética , Genes de Imunoglobulinas , Região Variável de Imunoglobulina/genética , Nefrite Lúpica/imunologia , Animais , Anticorpos/genética , Anticorpos/imunologia , Anticorpos Anti-Idiotípicos/análise , Sequência de Bases , Clonagem Molecular , Feminino , Imunoglobulina G/análise , Glomérulos Renais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular
8.
J Immunol ; 142(12): 4500-6, 1989 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-2786035

RESUMO

We have studied 18 anti-DNA secreting hybridomas derived from a single, nephritic NZB/NZW mouse. The antibodies were analyzed for the expression of idiotypic families that are enriched in the antibodies to DNA from diseased animals (IdGN2 and IdX), and for the expression of VH and V kappa gene segment subfamilies. Most of the mAb have characteristics similar to those that may be pathogenic because they 1) bound to native DNA, 2) were of the IgG2a or IgG2b isotype, and 3) expressed idiotopes associated with glomerulonephritis in NZB/NZW mice and human lupus. Among the 18 mAb, at least six VH subfamilies and six V kappa subfamilies were expressed. A majority of the antibodies utilized a VH gene segment from the large J558 subfamily. Slot blot analyses of total spleen cell RNA revealed that as NZB/NZW mice aged and developed nephritis, they expressed progressively higher quantities of Ig transcripts. The proportion of these transcripts derived from the VH J558 subfamily also increased. Our results indicate that a diversity of B cell clones participate in the anti-DNA response of a single NZB/NZW mouse. There was no preferential utilization of 3' Ig V gene segment subfamilies. Furthermore, there was no marked difference in the pattern of VH and V kappa gene segment expression in antibodies defined by their isotypes or idiotopes.


Assuntos
Anticorpos Antinucleares/genética , Diversidade de Anticorpos , DNA/imunologia , Genes de Imunoglobulinas , Região Variável de Imunoglobulina/genética , Animais , Anticorpos Antinucleares/análise , Feminino , Hibridomas/análise , Idiótipos de Imunoglobulinas/análise , Idiótipos de Imunoglobulinas/genética , Isotipos de Imunoglobulinas/análise , Isotipos de Imunoglobulinas/genética , Região Variável de Imunoglobulina/análise , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NZB , Baço
9.
Arthritis Rheum ; 32(5): 513-22, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2655604

RESUMO

Indirect immunofluorescence with monoclonal antibodies to 6 different idiotypes was used to characterize immunoglobulins deposited in the glomeruli of renal biopsy samples from 32 patients with systemic lupus erythematosus (SLE) and 19 patients with nonlupus immune glomerulonephritis. IdGN2 was present in 75% of the biopsy specimens from SLE patients and in 6% of those from patients with non-lupus nephritis; IdGN1 occurred in 38% and 6%, respectively. The other idiotypes were not increased in biopsy samples from patients with SLE. Deposition of IdGN2 was associated with a subendothelial location of Ig and proliferative changes in the glomeruli. In studies of glomerular eluates from 4 immunosuppressed SLE patients, an average of 26% of total Ig and 37% of anti-DNA was composed of IdGN2. Compared with IdGN2- immunoglobulin, IdGN2+ immunoglobulin was enriched in IgG1 in all 4 eluates, and was enriched in high-avidity anti-DNA in 2 eluates. IdGN2 is a marker of antibody subsets that are characteristic of SLE and are associated with severe lupus nephritis.


Assuntos
Idiótipos de Imunoglobulinas/análise , Glomérulos Renais/imunologia , Nefrite Lúpica/imunologia , Adulto , Anticorpos Monoclonais/imunologia , Afinidade de Anticorpos , Feminino , Imunofluorescência , Glomerulonefrite/imunologia , Humanos , Idiótipos de Imunoglobulinas/imunologia , Masculino
10.
Am J Med ; 85(6A): 32-4, 1988 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-3264458

RESUMO

A mechanism for sustained production of pathogenic autoantibody subsets in patients and mice with systemic lupus erythematosus may be centered on selective up-regulation of B cells bearing certain idiotypes. Public idiotypes are characteristic of some autoantibodies, including anti-DNA. Evidence is reviewed that suggests that immunoglobulins bearing certain public idiotypes, such as IdGN2, contain autoantibody subsets that are nephritogenic in human systemic lupus erythematosus and in New Zealand black/New Zealand white F1 mice. Up-regulation of such cells could promote development of nephritis. Work from several laboratories has shown that production of immunoglobulin G antibodies to DNA depends upon T cell help. In New Zealand black/New Zealand white F1 mice, cloned T cells are dominated by autoreactive cells that produce B cell growth factors. We suggest that this sustained release of B cell growth factors combined with selection by T helper cells for B cells bearing IdGN2 are a major mechanism for sustained up-regulation of nephritogenic subsets of autoantibodies.


Assuntos
Linfócitos B/imunologia , Idiótipos de Imunoglobulinas/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T/fisiologia , Animais , Autoanticorpos/imunologia , DNA/imunologia , Humanos , Camundongos , Linfócitos T/metabolismo
11.
J Autoimmun ; 1(1): 47-61, 1988 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3267108

RESUMO

We propose that a major immunoregulatory abnormality in murine and human autoantibody-mediated disease is idiotypic spreading. By this mechanism, B cells with the genetic information to produce immunoglobulin (Ig) bearing certain public idiotypes (Ids) are selectively upregulated, probably by Id-recognizing helper T cells. The model in which we are testing the hypothesis is systemic lupus erythematosus (SLE) in humans and NZB/NZW F1 (BW) female mice. Recent experiments have shown that the number of public Ids expressed on the Ig of nephritic BW mice is quite restricted. IdX is the dominant Id on serum Ig; IdGN1 and IdGN2 are also common. All three Ids were initially derived from spontaneous antibodies to DNA. Together the three are present on 85% of the total Ig repertoire. Such restriction suggests idiotypic spreading. In glomerular Ig deposits from nephritic BW mice, IdGN1 and IdGN2 are found on 45% of the total Ig: IdX is present in minute amounts. Furthermore, suppression of IdGNs by administration of anti-IdGN1 to BW mice resulted in significant delay in the onset of nephritis, but the IdGNs escaped from control and eventually caused a fatal nephritis. Finally, studies of glomerular Ig deposits in renal biopsies of patients with SLE have shown that IdGN2 dominates such Ig, being present in 76% of renal biopsies from SLE patients and in 6% from patients with non-lupus immune nephritis. Therefore, we have concluded that IdGN1 and IdGN2 are markers of nephritogenic subsets of autoantibodies and are probably the products of idiotypic spreading most likely to cause disease. Finally, after a review of recent experiments suggesting the dominance of autoreactive, Mossman Type 2 T helper cells in nephritic BW mice, it is hypothesized that autoreactive, IdGN-recognizing helper T cells may be central to the sustained upregulation of pathogenic autoantibodies in murine and human SLE.


Assuntos
Autoanticorpos/biossíntese , Idiótipos de Imunoglobulinas/imunologia , Animais , Doenças Autoimunes/imunologia , Reações Cruzadas , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Linfócitos T/imunologia
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