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1.
Andrologia ; 40(2): 81-3, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18336455

RESUMO

The worldwide prevalence of tuberculosis (TB) is still high, remaining almost unchanged over the past century. The genitourinary tract belongs to one of the most common sites of extrapulmonary TB. Although rare, epididymal TB may be the only clinically evident location of infection. We present an unusual case of tuberculous epididymitis and prostatitis, demonstrating the need for insistent diagnostic procedures to confirm diagnosis. The treatment of choice is primarily medical, consisting of a combination of three or four anti-TB drugs, sometimes combined with surgery.


Assuntos
Mycobacterium tuberculosis/patogenicidade , Orquite/diagnóstico , Prostatite/diagnóstico , Tuberculose dos Genitais Masculinos/diagnóstico , Adulto , Antituberculosos/uso terapêutico , Humanos , Masculino , Orquite/tratamento farmacológico , Orquite/microbiologia , Próstata/microbiologia , Prostatite/tratamento farmacológico , Prostatite/microbiologia , Testículo/microbiologia , Tuberculose dos Genitais Masculinos/tratamento farmacológico , Tuberculose dos Genitais Masculinos/microbiologia
3.
Diabetes Care ; 5 Suppl 2: 126-8, 1982.
Artigo em Inglês | MEDLINE | ID: mdl-6765522

RESUMO

Bovine and porcine insulins elicit specific antibody response in diabetic subjects after a few months of treatment. In seven type I diabetic individuals who were exclusively treated with human insulin (recombinant DNA) each month, sera were examined for the development of insulin-specific IgG and IgE antibodies. In all patients (except one), IgG antibodies occurred after 2 mo and tended to further increase in concentration after 5-6 mo. IgE antibodies could be detected after 1 mo with a further increase after 2-3 mo and a marked decline thereafter. No patient exhibited allergic symptoms. The results indicate that physicochemical properties of insulin preparations used for treatment and the route of administration are of more importance for immunogenicity than species differences of insulin.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Anticorpos Anti-Insulina , Insulina/uso terapêutico , Adolescente , Adulto , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Proteínas Recombinantes/uso terapêutico
4.
Diabetes Care ; 4(2): 170-4, 1981.
Artigo em Inglês | MEDLINE | ID: mdl-7011720

RESUMO

A preliminary study was performed to estimate the effect of biosynthetic human insulin (BHI) produced by the Eli Lilly Company in comparison with purified pork insulin (PPI) from the same manufacturer. Immunologic studies were done using an intradermal skin test with both insulins and in vitro studies binding with sera containing preformed antibodies against bovine and pork insulin. The studies were undertaken in eight healthy volunteers aged 24-31 yr. Insulin was given subcutaneously in an amount of 0.1 U/kg and 3 days later intravenously in an amount of 0.03 U/kg injected slowly over 1 min. Blood glucose, insulin, C-peptide, and growth hormone were measured at different times between 0 and 360 min. It was shown that BHI and PPI behaved similarly in lowering blood glucose, suppressing C-peptide, and increasing growth hormone via hypoglycemic action. After s.c. injection, BHI was found to reach higher serum concentrations after 60 min than PPI. Correspondingly, the blood glucose curve was significantly lower after BHI than after PPI. This difference was not observed after the i.v. application of both forms of insulin.


Assuntos
Insulina/farmacologia , Adulto , Animais , Glicemia/metabolismo , Peptídeo C/sangue , Diabetes Mellitus/sangue , Hormônio do Crescimento/sangue , Humanos , Hidrocortisona/sangue , Insulina/sangue , Anticorpos Anti-Insulina/análise , Masculino , Ovinos , Testes Cutâneos , Especificidade da Espécie , Suínos
5.
Thromb Haemost ; 83(6): 853-60, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10896238

RESUMO

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of


Assuntos
Líquido da Lavagem Broncoalveolar/química , Fibrina/metabolismo , Doenças Pulmonares Intersticiais/metabolismo , Tromboplastina/metabolismo , Adolescente , Adulto , Idoso , Alveolite Alérgica Extrínseca/metabolismo , Antifibrinolíticos/metabolismo , Fatores de Coagulação Sanguínea/metabolismo , Relação CD4-CD8 , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Hemostáticos/metabolismo , Humanos , Complacência Pulmonar , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neutrófilos , Fibrose Pulmonar/metabolismo , Sarcoidose/metabolismo
6.
Anticancer Res ; 20(6D): 5053-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11326667

RESUMO

The study presents data comparing the new tumor marker Tumor M2-PK with CEA, CYFRA 21-1, NSE and SCC in the diagnosis of lung cancer. Tumor M2-PK is quantitatively detectable in EDTA-plasma with a sensitive ELISA. The results of the tumor marker test were compared with respect to the different histological tumor types and with the tumor staging. So far 144 newly diagnosed lung cancer patients were included. Significantly elevated tumor marker concentrations were found with progressive tumor stages. The best correlation with the tumor stage was observed for Tumor M2-PK and CYFRA 21-1. Comparison of the sensitivities in the detection of lung cancer indicated that the Tumor M2-PK-test (sensitivity: 58%) is more efficient than the CEA-Test (sensitivity: 39%) or CYFRA 21-1 (sensitivity: 48%). Generally higher sensitivity for non-small cell lung cancer only was shown for Tumor M2-PK (sensitivity: 65%), CEA (sensitivity: 42%) and CYFRA 21-1 (sensitivity: 58%). For small-cell lung cancer the marker NSE was more sensitive than all other markers. Initial follow-up studies indicate that Tumor M2-PK and CYFRA 21-1 can be used to monitor disease with tumor progression or regression during chemotherapy. The present data indicated that Tumor M2-PK could be a valuable tumor marker for the detection of lung cancer.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Pulmonares/diagnóstico , Serpinas , Antígenos de Neoplasias/sangue , Antígeno Carcinoembrionário/sangue , Humanos , Queratina-19 , Queratinas , Neoplasias Pulmonares/sangue , Estadiamento de Neoplasias , Prognóstico , Piruvato Quinase/sangue
7.
Clin Exp Med ; 2(4): 185-91, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12624710

RESUMO

Tumor markers were used for disease monitoring in small-cell lung cancer patients. The aim of this study was to improve diagnostic efficiency in the detection of tumor progression in small-cell lung cancer patients by using fuzzy logic modeling in combination with a tumor marker panel (NSE, ProGRP, Tumor M2-PK, CYFRA 21-1, and CEA). Thirty-three consecutive small-cell lung cancer patients were included in a prospective study. The changes in blood levels of tumor markers and their analysis by fuzzy logic modeling were compared with the clinical evaluation of response versus non-response to therapy. Clinical monitoring was performed according to the standard criteria of the WHO. Tumor M2-PK was measured in plasma with an ELISA, all other markers were measured in sera. At 90% specificity, clinically detected tumor progression was found by the best single marker, NSE, in 32% of all cases. A fuzzy logic rule-based system employing a tumor marker panel increased the sensitivity significantly (P>0.0001) in small-cell carcinomas to 67% with the threemarker combination NSE/ProGRP/Tumor M2-PK and to 56% with the best two-marker combination ProGRP/Tumor M2-PK, respectively. An improvement of sensitivity was also observed using the two-marker combination of ProGRP/NSE (sensitivity 49%) or NSE/Tumor M2-PK (sensitivity 52%). The fuzzy classifier was able to detect a higher rate of progression in small-cell lung cancer patients compared with the multiple logistic regression analysis using the marker combination NSE/ProGRP/Tumor M2-PK (sensitivity 44%; AUC=0.76). With the fuzzy logic method and different tumor marker panels (NSE, ProGRP and Tumor M2-PK), a new diagnostic tool for the detection of progression in patients with small-cell lung cancer is available.


Assuntos
Carcinoma de Células Pequenas/diagnóstico , Lógica Fuzzy , Neoplasias Pulmonares/diagnóstico , Idoso , Biomarcadores Tumorais , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Análise de Regressão , Sensibilidade e Especificidade
9.
Immun Infekt ; 13(4): 135-8, 1985 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-4030009

RESUMO

Two years ago, the foundation "Deutscher Polleninformationsdienst" was established in Cologne/West Germany. Measurements from pollen collectors, together with the weather forecast were combined to a prognosis of pollen flight for the following 2 days. In spring and summer, these informations were given to the public services twice a week. Now, in nearly all regions of West Germany, pollen measurement points are established. The aim of a pollen information service is to give further information to pollinosis patients and physicians on their medicaments, i.e. how to use them effectively and prophylactically.


Assuntos
Serviços de Informação , Pólen , Rinite Alérgica Sazonal/prevenção & controle , Alemanha Ocidental , Humanos , Serviços Preventivos de Saúde
10.
Dtsch Med Wochenschr ; 106(4): 115-20, 1981 Jan 23.
Artigo em Alemão | MEDLINE | ID: mdl-7472183

RESUMO

Acute exogenous allergic alveolitis with the typical symptoms of unproductive cough, dyspnoea on exertion, fever, loss of weight, headache and limb pains was observed in a 24-year-old bank employee. Leucocytosis was accompanied by raised ESR; pronounced hypoxaemia and marked restrictive ventilatory defects were found. X-ray changes consisted of severely increased fine reticular interstitial shadowing. The differential diagnosis of allergic alveolitis was confirmed by the demonstration of precipitating antibodies in serum against Pullularia pullulans, Trichoderma viride, Cephalosporium acremonium and Aspergillus fumigatus, moulds with an ubiquitous occurrence. Typical changes of alveolitis were found histopathologically and immunohistologically in the lung tissue after a mini-thoracotomy. The source of exposition leading to the disease were pot plant earth and containers in the patient's flat. Moulds could be isolated from these substrates.


Assuntos
Alveolite Alérgica Extrínseca/etiologia , Pneumopatias Fúngicas/etiologia , Fungos Mitospóricos , Adulto , Alveolite Alérgica Extrínseca/microbiologia , Alveolite Alérgica Extrínseca/patologia , Biópsia , Humanos , Pulmão/microbiologia , Pulmão/patologia , Pneumopatias Fúngicas/microbiologia , Masculino , Microbiologia do Solo , Esporos Fúngicos
11.
Pneumologie ; 44 Suppl 1: 569-71, 1990 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-2367472

RESUMO

Bronchial hyperreactivity is the central symptom of bronchial asthma which, however, can also be observed in various other diseases affecting the lungs and bronchi, such as, for example, sarcoidosis. In response to unspecific inhalative provocation, obstruction of the bronchi occurs; a genetic predisposition is thought to be involved. During this reaction, histamine is released by various cells, predominantly mast cells. In comparison with normal subjects, patients with bronchial asthma, sarcoidosis or a hyperreactive bronchial system are found to have significantly higher basal plasma levels if histamine. In response to unspecific provocation with acetylcholine and Carbachol, significantly higher histamine levels are observed in bronchial asthma and sarcoidosis. Although an increase is also observed in normal subjects and hyperreactives, it is appreciably lower than in the other two groups of patients. In contrast to asthmatics and patients with sarcoidosis, in particular in patients with hyperreactivity, a significant increase in plasma histamine is found following ergometer exercise. These results show that endogenous histamine is liberated by provocation challenges in various diseases, and may have a possible influence on bronchial obstruction.


Assuntos
Asma/diagnóstico , Testes de Provocação Brônquica/métodos , Histamina/sangue , Pneumopatias/diagnóstico , Hipersensibilidade Respiratória/diagnóstico , Sarcoidose/diagnóstico , Acetilcolina , Asma/sangue , Carbacol , Humanos , Pneumopatias/sangue , Hipersensibilidade Respiratória/sangue , Sarcoidose/sangue
12.
Immun Infekt ; 5(5): 179-83, 1977 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-410729

RESUMO

Disodium cromoglycate (Intal) has been found several years ago to act as an reliable drug in the treatment of allergic states of the respiratory system. The effective mechanism seems to be its stabilizing function for circulating and sessile mast cells, thus avoiding the release of histamine and other vasoactive amines after an immunological or non-immunological stimulus. Although DSCG does not inhibit the binding of antigen to its antibody it must be given prophylactically before the antigen has access to the mast cells. Most efficiently DSCG is used in the treatment of the exogenous allergic asthma, and secondly in allergic rhinitis (70-90% success). Own observations confirm the effectiveness of the drug especially in patients with pollinosis. In addition it was found that DSCG can be used during hyposensitization procedures and that the drug does not influence the results of skin testing. At present there have been detected neither side-effects nor interactions with other drugs.


Assuntos
Asma/tratamento farmacológico , Cromolina Sódica/uso terapêutico , Rinite Alérgica Sazonal/tratamento farmacológico , Adulto , Bronquite/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Dessensibilização Imunológica , Feminino , Humanos , Mastócitos/efeitos dos fármacos
13.
Monatsschr Kinderheilkd ; 137(3): 158-61, 1989 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-2541330

RESUMO

We studied the concentration of angiotensin-converting enzyme (ACE) in 80 respiratory and hepatologic healthy patients aged 4 months to 35 years. The normal values ranged from 9.4-38.8 U/ml with a tendency of lower ACE-concentrations in the older patients. In the follow up of 16 patients with hypersensitivity pneumonitis a decrease of initially elevated values of ACE was observed in 12 cases. In two patients with a recurrent course of hypersensitivity pneumonitis ACE rose to levels above 30 U/ml. These findings suggest that ACE-concentration in serum is an additional parameter to evaluate the acute stage of disease in patients with hypersensitivity pneumonitis.


Assuntos
Alveolite Alérgica Extrínseca/enzimologia , Peptidil Dipeptidase A/sangue , Adolescente , Adulto , Alveolite Alérgica Extrínseca/diagnóstico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino
14.
Immun Infekt ; 13(1): 21-3, 1985 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-2579893

RESUMO

An increased alpha-2-macroglobulin level and a decreased functional capacity of the mononuclear phagocytic system in diabetics appears to be another important factor in the pathogenic cause of micro- and macro-angiopathy. Additionally, the disturbed immunobalance, especially in the micro-environment as well as the type and intensity of infections and inflammatory reactions are involved.


Assuntos
Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/imunologia , Falência Renal Crônica/imunologia , alfa-Macroglobulinas/metabolismo , Angiopatias Diabéticas/imunologia , Humanos , Técnicas Imunológicas , Fagocitose
15.
Immun Infekt ; 6(4): 146-52, 1978 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-150399

RESUMO

Allergic reactions of the immediate type to insulin are known since its introduction of the treatment of diabetes mellitus. After the development of the chromatographically purified insulins they are to be found significantly reduced, though still particular cases are observed. The simultaneous occurrence of insulin allergy and insulin resistance seems to be not too rare. The immediate type allergy to insulin is mostly released by the presence of IgE-antibodies. Another but not at all rare allergic reaction is the Arthus phenomenon, released by IgG-antibodies. For diagnosis of these allergic states intradermal skin tests with various insulins are used. Also specific IgE-antibodies are to be measured radioimmunologically lately. There is a strong correlation between the outcome of the allergic reactions and the definite degree of the specific IgE-antibodies. Low levels of specific IgE are found in insulin treated diabetics without any visible allergic reactions to insulin. This fact proves that the hormone, though being a clean insulin of a very high degree, is the antigen itself. Not only immunologic mechanism, but also other exogenic influences cause allergic reactions of the immediate type to insulin.


Assuntos
Hipersensibilidade Imediata/imunologia , Adulto , Reação de Arthus/imunologia , Diabetes Mellitus/tratamento farmacológico , Hipersensibilidade a Drogas/imunologia , Humanos , Imunoglobulina E/análise , Imunoglobulina G/análise , Insulina/imunologia , Insulina/uso terapêutico , Anticorpos Anti-Insulina , Resistência à Insulina , Masculino , Pessoa de Meia-Idade
16.
Pneumologie ; 44 Suppl 1: 538-9, 1990 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-2367459

RESUMO

Employing routine clinical methods, the pulmonary function of 21 type 1 diabetics prior to and after exercise, was examined. In type 1 diabetics, at the time of the manifestation of the disorder, a reversible, seemingly metabolism-related emphysematous expansion was to be seen. In comparison with a control group and diabetics with no late complications, type 1 diabetics with secondary complications proved to have a significantly reduced vital and total capacity with relative hyperexpansion; an obstructive ventilation disorder was not demonstrable. These results are confirmed by those reported in the literature, and suggest the existence of a diabetic pneumopathy.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Teste de Esforço , Medidas de Volume Pulmonar , Adulto , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Pulmão/fisiopatologia , Masculino , Oxigênio/sangue
17.
Dtsch Med Wochenschr ; 100(43): 2198-203, 1975 Oct 24.
Artigo em Alemão | MEDLINE | ID: mdl-1080704

RESUMO

Antinuclear factors were demonstrated during D-penicillamine treatment in patients with rheumatiod arthritis (72) and scleroderma (7). While in 13 antinuclear factors were demonstrable already before treatment was started, they occurred in the course of treatment in another 34. D-penicillamine administration had to be discontinued in 18 because of severe side effects, with a marked correlation between their severity and the presence of antinuclear factors. Side effects requiring stoppage of the drug were especially common in patients who had antinuclear factors even before onset of treatment. The severest complication of D-penincillamine treatment, renal damage, was found only in patients with antinuclear factors, in this instance antibodies against denatured DNA. The following therapeutic consequences should be drawn from these findings: (1) D-penicillamine should, if possible, not be given to any patient with antinuclear factors; (2) in patients in whom antinuclear factors occur in the course of D-penicillamine treatment but its administration is to be continued, blood picture, renal functions and urine must be regularly tested.


Assuntos
Anticorpos Antinucleares/análise , Penicilamina/uso terapêutico , Adulto , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Humanos , Nefropatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Penicilamina/efeitos adversos , Prognóstico , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/tratamento farmacológico
18.
Dtsch Med Wochenschr ; 113(28-29): 1142-5, 1988 Jul 15.
Artigo em Alemão | MEDLINE | ID: mdl-3292191

RESUMO

A 48-year-old woman with diabetes mellitus (type IIb) had to be treated with insulin because of poor blood-sugar control. Infiltrates at the sight of injection occurred with two different porcine insulin preparations, necessitating a switch to human insulin. After the third injection of the latter an anaphylactic reaction developed within minutes. During a pregnancy in 1968 the patient had briefly received bovine insulin. Tests now revealed an immediate-type allergy against all three available species insulins, which was successfully treated by hyposensitisation.


Assuntos
Anafilaxia/induzido quimicamente , Dessensibilização Imunológica , Insulina/efeitos adversos , Anafilaxia/prevenção & controle , Animais , Bovinos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Insulina/imunologia , Anticorpos Anti-Insulina/análise , Pessoa de Meia-Idade , Gravidez , Gravidez em Diabéticas/tratamento farmacológico , Especificidade da Espécie , Suínos , Fatores de Tempo
19.
Dtsch Med Wochenschr ; 115(51-52): 1950-5, 1990 Dec 21.
Artigo em Alemão | MEDLINE | ID: mdl-2261860

RESUMO

A 72-year-old man with recurrent hypoglycaemia was suspected of having an insulinoma. But several diagnostic methods (computed tomography; mesenteric and coeliac angiography; sella imaging) did not reveal any tumour. 72-hour hunger test did not precipitate any spontaneous hypoglycaemia. A falling insulin-glucose ratio spoke against an insulin-producing tumour. Reactive symptomatic hypoglycaemia occurred 4.5 hours after an oral glucose test. Measurement of insulin concentration demonstrated a slow but pronounced increase (3500 microU) over an already raised initial value (816 microU/ml), typical of prediabetic metabolic regulation. Demonstration of insulin autoantibodies confirmed the diagnosis of an insulin autoimmune syndrome, which has a good prognosis. The patient became free of symptoms on a regimen of frequent small, carbohydrate-poor but fat and bulk-rich meals. Hypoglycaemia recurred when the diet was not observed.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/complicações , Hipoglicemia/etiologia , Anticorpos Anti-Insulina/sangue , Idoso , Doenças Autoimunes/dietoterapia , Glicemia/análise , Artéria Celíaca/diagnóstico por imagem , Diagnóstico Diferencial , Teste de Tolerância a Glucose , Humanos , Hipoglicemia/dietoterapia , Insulina/sangue , Insulinoma/diagnóstico , Masculino , Artérias Mesentéricas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico , Prognóstico , Recidiva , Síndrome , Tomografia Computadorizada por Raios X
20.
Immun Infekt ; 18(3): 89-90, 1990 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-2379932

RESUMO

A 54-year-old female presenting with arthralgias, weight loss, and anemia developed Raynaud's phenomenon and subcutaneous nodules at her hands. Granulomatous inflammation was observed in biopsies taken from her hands and sinuses, and later on the patient suffered from glomerulonephritis. The diagnosis Wegener's granulomatosis was further supported by detection of anticytoplasmic antibodies.


Assuntos
Granulomatose com Poliangiite/diagnóstico , Feminino , Glomerulonefrite/etiologia , Mãos , Humanos , Artropatias/etiologia , Pessoa de Meia-Idade , Doença de Raynaud/etiologia , Pele/patologia , Dermatopatias/etiologia
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