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Background:Since the advent of Tyrosine Kinase Inhibitor (TKI), well controlled studies in developed world have shown that the life expectancy of patients with CML is comparable to normal people without the disease. But long-term follow up studies are lacking in resource poor setting. Methods:This is a retrospective follow up study looking at the molecular response and resistance to Tyrosine Kinase Inhibitors (TKI) in patients enrolled in the Max Access Program since February 2003 till March 2017. Patients with twoor more BCR-ABL1 levels by Karyotyping/ fluorescent in situ hybridization (FISH) / reverse transcriptase polymerase chain reaction (RT-PCR) were included. At baseline, complete blood count (CBC), renal function test (RFT), and liver function test (LFT) were evaluated. Bone marrow aspiration and biopsy for morphology, cytogenetic analysis by Karyotyping/FISH and/or molecular analysis by RT-PCR were also done if these tests were not performed earlier. FISH or RT-PCR was done on peripheral blood every 3–12 months as necessary if the patient could afford. Patients with warning response/failure underwent BCR-ABL1 Resistance Mutation Analysis (IRMA).Results:Three hundred and forty six (346) patients had two or more BCR-ABL1 monitoring tests done. Optimal response was seen in 49.42%. Similarly, suboptimal response and failure were seen in 16.5% and 34% respectively. Overall Survival is 89.6% (at 1.8 -165 months, mean 62 months) . If only CML related events is considered survival is 95.9%. Seventy seven (77) patients with a total of 80 BCR-ABL1 domain Imatinib Resistance Mutation Analyses (IRMA) showed 19 different types of mutations with the most common being T315I mutation (8 and 19.5%). About 22.25% of the total patients showed resistance to Glivec out of which 10.98% showed mutations. Nine patients underwent trial for treatment free response (TFR) and 5 of them relapsed between 2-8 months.Conclusions:Despite all the odds of having financial problem, accessibility problem due to distances, transportation, etc. and difficulty monitoring with routine BCR-ABL1 and IRMA, our findings show that the outcome of TKI therapy in our CML patients is comparable to well controlled studies done elsewhere. Overall survival, molecular and cytogenetic responses and mutations in our patients who developed resistance as well as TFR are also similar to other studies. The resistance rate of 22.25% is slightly higher compared to other studies in developed world. This is mainly because of poor monitoring due to unavailability of the test including IRMA in our country and affordability until 2012. It proves that TKI is very effective in CML even in a resource-poor, developing country
ABSTRACT
Rhodococcus equi é um micro-organismo intracelular facultativo, agente etiológico da rodococose, uma importante enfermidade que acomete principalmente potros com menos de seis meses de idade, causando a morte geralmente em decorrência de lesões pulmonares. Este agente também tem potencial zoonótico e emergiu como um patógeno oportunista no mundo, acometendo humanos imunocomprometidos, especialmente os transplantados e infectados pelo vírus da imunodeficiência humana (HIV). Entretanto, infecções por R. equi em hospedeiros hígidos tem sido relatadas, principalmente em crianças e idosos. Estudos tem mostrado um nível crescente na resistência de isolados de R. equi em relação aos antimicrobianos comumente utilizados no tratamento de animais e seres humanos infectados por este agente. A virulência deste pode estar associada a fatores como a cápsula de polissacarídeo, fosfolipase C e à enzima colesterol oxidase (fator equi). No entanto, uma proteína localizada em um plasmídeo, designada vapA, é essencial para a sobrevivência e replicação do agente em macrófagos. Com isso, os objetivos deste estudo foram avaliar o perfil de suscetibilidade de isolados de R. equi de diferentes fontes em relação aos antimicrobianos mais comumente utilizados na terapêutica animal e humana, bem como verificar a associação entre a presença do gene vapA e o índice de resistência múltipla aos antimicrobianos (IRMA). Neste estudo, 67 isolados brasileiros de R. qui de diferentes fontes foram analisados: 30 provenientes de amostras clínicas de equinos, sete de humanos e 30 ambientais (seis do solo e 24 de fezes de equinos). Para avaliar o perfil de suscetibilidade dos isolados utilizou-se o método de disco difusão, sendo testadas 16 drogas de diferentes classes de antimicrobianos. As amostras clínicas de equinos apresentaram as maiores taxas de resistência à penicilina (86,7%) e lincomicina (30%). Além disso, foram também resistentes a macrolídeos (azitromicina a 6,7%, eritromicina a 6% e ...
Rhodococcus equi is a facultative intracellular bacterium and etiological agent of rodococosis, an important disease that affects specially foals under six months old and leading the death generally due to pulmonary lesions. R. equi also has zoonotic potential, and it has emerged as an opportunistic pathogen in the world, specially infecting solid organ transplant recipients and immunocompromised human patients, mainly those infected by human immunodeficiency virus (HIV). Additionally, R. equi infections by healthy hosts have been reported principally in children and elderly individuals. Studies have shown an increasing level of resistance of isolates of R. equi against antibiotics commonly used to treat affected animals and humans. The virulence of this agent is associated with a protein located on a plasmid, designated vapA, it is essential for survival and replication of R. equi within macrophages. The present study evaluated the susceptibility profile of R.equi isolates from different sources against the antimicrobials most commonly used to treat animals and humans, as well as the occurrence and association of vapA gene and the antimicrobial multiple resistance index (AMRI). Sixty-seven Brazilian isolates of R. equi from different sources were analyzed: 30 clinical samples of horses, seven of human and 30 of environmental (six from soil and 24 from horse feces). To evaluate the susceptibility profile of R. equi isolates, the Kirby Bauer method was performed by using 16 drugs of 11 distinct antimicrobials classes. Additionally, those samples were also resistant to macrolides (azithromycin 6.7%, erythromycin 6% and clarithromycin 3.3%) as well as rifamycin (13%). All human and environmental samples were sensitive to macrolides and rifamycin. However, environmental isolates demonstrated high levels of resistance to penicillin and chloramphenicol. Similarly, human isolates had high level of resistance to ceftiofur, lincomycin and sulfazotrim. AMRI...
Subject(s)
Animals , Disease Susceptibility/microbiology , Disease Susceptibility/veterinary , Drug Resistance, Bacterial , Erythromycin , Rhodococcus equiABSTRACT
Background & objectives: Estimation of parathyroid hormone (PTH) levels is important in the management of metabolic bone disorders. Here we describe a simple, sensitive and specific second generation immunoradiometric assay (IRMA) to detect intact PTH levels using different solid phase matrices. Different methods for immobilization of antibodies have also been evaluated. Methods: Experiments were carried out with physical adsorption of antibodies, covalent coupling using 2 per cent glutaraldehyde and N,N`carbonyldiimidazole. In all cases, antibodies raised against C-terminal were used as solid phase agent. Detector antibodies were N terminal antibodies that were radio-iodinated with 125I followed by gel purification. Several of the antibodies coupled to various solid phase matrices were incubated with PTH standards and the detector antibody as well as the commercially available tracer from DiaSorin kit to identify a suitable match pair. Results: The best pair was polyclonal C-terminal PTH antibody along with the kit tracer from DiaSorin with regards to antibody coated to magnetic cellulose particles. Among the various antibodies and the solid phases evaluated, the best assay was obtained with the matched pair of antibodies (70×G67 and 70×G68) from Fitzgerald immobilized on polystyrene tubes. The polyclonal antibody against C-terminal PTH was chosen as the capture antibody and 125I labelled polyclonal antibody against N-terminal PTH as the tracer. The sample values obtained in the antibody coated tubes were comparable to those obtained using a commercial kit. Interpretation & conclusions: The results indicated the feasibility of adopting this system for further development into a PTH IRMA for regular production as there is no indigenous kit available for intact PTH.
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Apresenta diferentes concepções em torno dos êxtases de uma beata (Irmã Germana) que viveu em Minas Gerais no século XIX, o parecer do médico Antônio Gonçalves Gomide, seguido do exame de dois cirurgiões e da narrativa do naturalista Auguste de Saint-Hilaire. O objetivo é situar historicamente os textos, investigando as orientações teóricas dos autores e o modo como analisaram os êxtases da beata. A publicação dos documentos pode contribuir para o estudo dos saberes médico-mentais em inícios do século XIX no Brasil.
The article presents two different views of the ecstasies of a nun (Sister Germana) who lived in Minas Gerais, Brazil, in the nineteenth century. The first perspective was the opinion of Dr. Antônio Gonçalves Gomide, together with an examination by two surgeons; the second was a narrative by the naturalist Auguste de Saint-Hilaire. The goal is to historically situate the texts, investigate the theoretical orientations of the authors and note how they analyzed the woman's moments of ecstasy. The publication of these texts contributed to the study of medical and mental knowledge in the early 19th century in Brazil.
Cet article présente les différents aspects de l'extase d'une religieuse (la Sur Germana) qui a vécu dans l'État de Minas Gerais au XIXe siècle, l'avis de son médecin Antonio Gonçalves Gomide, suivi de l'examen de deux chirurgiens et le récit du naturaliste Auguste de Saint-Hilaire. Notre travail est de situer historiquement les textes, d'enquêter sur les orientations théoriques des auteurs et sur la façon dont ils ont analysé l'extase de la sainte. Cet article a comme but de contribuer à l'étude des connaissances médicales et mentales au Brésil au début du XIXe siècle.
Se presentan diferentes concepciones acerca de los éxtasis de una beata (Sor Germana) que vivió en Minas Gerais en el siglo XIX, la opinión del médico Antônio Gonçalves Gomide, seguido por el examen de dos cirujanos y la narrativa del naturalista Auguste de Saint-Hilaire. El objetivo es situar históricamente los textos, investigando las orientaciones teóricas de los autores y el modo como analizaron los éxtasis de la beata. La publicación de los documentos puede contribuir para el estudio de los saberes médico-mentales en los inicios del siglo XIX en Brasil.
Subject(s)
Humans , Female , History, 19th Century , Nervous System Diseases , Psychiatry/history , CatalepsyABSTRACT
O autor se propõe a demonstrar, na transição do sonho da injeção de Irma ao caso Emma, do Entwurf..., o reposicionamento subjetivo de Freud, coextensivo a seu afastamento de Fliess, que lhe permitiu abordar a questão do sexual fora do discurso provedor de sentido.
The author intends to demonstrate, in the transition from the dream of Irma's injections to the Emmas case of the Entwurf , the subjective repositioning of Freud, linked to his separation of Fliess, which allowed him to treat the question of the sexual condition outside of a sense providing speech .
Subject(s)
Sexuality , Psychoanalytic Theory , Neurotic DisordersABSTRACT
Thyroid-stimulating hormone (TSH) is the most sensitive marker reflecting thyroid function. TraditionaUy, TSH concentration was measured by the method of RadioImmunoAssay (RIA) with the detection limits around 1 to 2 mIU/L, which was unable to differentiate hyperthyroid status. Since 1980s, owing to the sensitive assay for TSH, immunoradiometric assay (IRMA), it has been possible to detect low concentration of TSH by 0.001 mlU/L. TSH is composed of two glycopeptide subunits, a-subunit and B-subunit. Monoclonal antibodies, directed against two different sites of the TSH peptides, are used in IRMA. One antibody is directed toward the specific B-subunit of TSH molecule and is used to extract it from serum, a second antibody labelled with a radioactive material is then attached to the separated TSH to form "sandwhich" molecule that can be measured. Generally, mouse monoclonal antibodies are used as capture and detection antibodies. Infrequently, when there is heterophilic antibody, i.e. human anti-mouse antibody (HAMA), TSH can be measured as spuriously elevated, since HAMA may form a link between the signal and capture molecules. We report a case of inappropriately elevated TSH concentration due to heterophilic antibody, later diagnosed as Graves disease. A 41-year-old woman visited our clinic with the chief complaints of hand tremor, hyperphagia, weight loss for 3 months. Two years earlier, she underwent total colectomy due to colon cancer and had treat on multiple chemotherapies. The results of thyroid function test shows that TSH was 0.77 mIU/L, free T was 7.1 ng/dL (0.8~1.9), free T was 11.3 pg/mL (0.2~5.5). Thyroid specific auto- antibody results were anti-Tg-Ab 21.3 m/mL(0 100), anti-TPO-Ab 87.9m/mL(0100), TBIAb 7.8% (-15/15). Thyroid scan showed that radioactiveiodine uptake was increased and thyroid gland wasenlarged diffusely. Because TSH level was elevated, further evaluations were performed to differentiate with TSH producing pituitary tumor and pituitary resistance to thyroid hormone. Sellar MRI was normal, TRH stimulation test showed flat response. Since spurious elevation of TSH is possible at the presence of hetrophilic antibody, we rechecked TSH concentration after adding mouse monoclonal antibody to the patients serum with result of TSH less than 0.05 mIU/L. She was able to be diagnosed as Graves disease, and started with methimazole. Three months later, thyroid function test showed that TSH was 10.5 mIU/L, free T4 was 1.0 ng/dL, free T3 was 4.0 pg/mL. TSH level after removal the effect of heterophilic antibody with mouse monoclonal antibody was 0.71 mIU/L. Neutropenia was developed 5 months after methimazole therapy, to stop antithyroid medication. With the plan of radioactive iodine therapy if she relapses, she is being followed with periodic thyroid function test. We report a case of Graves disease with spuriously elevated TSH due to the effect of heterophilic antibodies.
Subject(s)
Adult , Animals , Female , Humans , Mice , Antibodies , Antibodies, Monoclonal , Colectomy , Colonic Neoplasms , Drug Therapy , Graves Disease , Hand , Hyperphagia , Immunoradiometric Assay , Iodine , Limit of Detection , Magnetic Resonance Imaging , Methimazole , Neutropenia , Peptides , Pituitary Neoplasms , Radioimmunoassay , Recurrence , Thyroid Function Tests , Thyroid Gland , Thyrotropin , Tremor , Weight LossABSTRACT
Os auto-anticorpos anti tireoglobulina (AAT) e antimicrossomal/peroxidase (AAM) estão altamente associados às doenças auto-imunes da tireóide e tem sido investigados por métodos diversos. O presente estudo foi realizado em um grupo de 108 pacientes oom doença da tireóide (Tireoidite de Hashimoto, n = 43; Doença de Graves - n = 13 e Bócio colóide - n = 52) e em 25 doadores sadios de banco de sangue do Hospital de Clínicas - UFPR. Os anticorpos AAM e AAT foram analisados simultaneamente pelo métodos de Aglutinação Passiva (AP), IRMA e Imunofluorescência Indireta (IFI) com o objetivo de padronizar este último em nosso serviço e compará-lo com os demais. A positividade para os AAM na Tireoidite de Hashimoto, na Doença de Graves e no Bócio colóide variou de 62,8% a 81,4%, 76,8% a 92,3% e 5,76% 19,2%, respectivamente. O coeficiente de relação dos níveis de anticorpos detectados pelos três métodos ressaltou alta significância(AAT,r=0,60 a 0,74 e AAM r=0,84 a 0,91; p< 0,01). A análise dos resultados evidenciou que embora para os AAM a IFI tenha apresentado sensibilidade ligeiramente inferior aos outros métodos, seu uso traria resultados mais confiáveis no laboratório clínico,com grande redução no custo da análise.
Subject(s)
Humans , Male , Female , Autoimmune Diseases , Clinical Laboratory Techniques , Crowding , Fluorescent Antibody Technique , Thyroid GlandABSTRACT
Objective:To explore the clinical value of gastric cancer by combined testing of the gastric juice and serum levels of CA72 - 4,CA19 - 9 and CEA. Methods :The gastric juice and serum levels of CA72 - 4,CA19 - 9 and CEA in 32 cases of all stages of gastric cancer and 20 cases of benign gastric disorders were determined preoperatively using IRMA method. Results: The results showed that the gastric juice, serum levels and the sensitivity rates of CA72 - 4, CA19 ~ 9 and CEA were significantly higher ( P
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Using a highly sensitive IRM A which can detect the hGH in urine directly, we measured the nocturnal urinary GH values in 13 normal men, 12 normal women, and 17 patients with acromegaly. The values were 0.58?0.56 ng, 0.52?0.37 ng, and 167.21 278.2 ng respectively. The nocturnal urinary GH secretion was significantly higher in the acromegalic patients than in the normal adulls (P