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1.
BMC Med Educ ; 21(1): 322, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090441

RESUMO

BACKGROUND: The traditional curriculum for medical students in Japan does not include sufficient opportunities for students to develop their skills for musculoskeletal (MSK) examination and clinical reasoning and diagnosis. Therefore, an effective programme is required to help medical students and residents improve their clinical skills in MSK. This paper aims to assess the clinical skills of medical students who have participated in a peer role-playing simulation programme using a mini clinical evaluation exercise (mini-CEX). METHODS: Participants were 90 female medical students who were completing their first orthopaedic clinical clerkship. They were divided into two groups. The simulation group participated in a role-play focussed on MSK cases as low-fidelity simulation, a structured debriefing with the course supervisor, and a self-reflection on Day 1 (n = 64). The control group did not participate in the role-play due to randomised clerkship schedules (n = 26). On Day 2 of the intervention, we observed and assessed all participants' performances during MSK outpatient encounters using the mini-CEX. We compared the mini-CEX score between the simulation group and the control group; the Wilcoxon rank-sum test was used for statistical analysis. RESULTS: The mini-CEX scores for physical examination, clinical reasoning and diagnosis, and overall clinical competency were significantly higher in the simulation group than in the control group (p < .05, physical examination: p = .014, clinical reasoning: p = .042, overall: p = .016). These findings suggest that medical students who partake in a peer role-playing simulation programme could experience improved clinical skills for physical examination, clinical reasoning and diagnosis, and overall clinical competency in real-life MSK outpatient encounters. CONCLUSIONS: Through a mini-CEX assessment, our findings indicate that medical students who participated in our peer role-playing simulation programme have improved clinical skills. Peer role-playing as a low-fidelity simulation and practical educational opportunity will enable educators to polish the competency of medical students in musculoskeletal physical examinations and clinical reasoning and diagnosis in a clinical setting.


Assuntos
Estágio Clínico , Competência Clínica , Feminino , Humanos , Japão , Exame Físico , Desempenho de Papéis
2.
Pediatr Int ; 59(2): 154-158, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27706892

RESUMO

BACKGROUND: Guidelines recommend avoiding excessive oxygen during neonatal resuscitation. Recent studies have suggested that oxygen titration can be achieved using a self-inflating bag, but data on the effectiveness of resuscitators used in neonatal ventilation are scarce, The aim of this study was therefore to determine the amount of oxygen delivered using several brands of neonatal self-inflating resuscitation bags without reservoirs under different conditions with regard to oxygen flow rate, ventilation rate (VR), peak inspiratory pressure (PIP) range, and test lung compliance. METHODS: Oxygen concentration was measured under a variety of conditions. Combinations of oxygen flow rate (10, 5.0, 3.0 and 1.0 L/min), VR (40, 60 inflations/min), PIP range (20-25 cmH2 O, 35-40 cmH2 O), and test lung compliance (0.6, 1.0, 3.0, and 5.0 mL/cmH2 O) were examined using six kinds of self-inflating bag. RESULTS: Delivered oxygen concentration varied widely (30.1-96.7%) and had a significant positive correlation with gas flow rate in all of the bags. Delivered oxygen concentration was also negatively correlated with PIP in all of the bags and with VR in some of them. Test lung compliance did not affect delivered oxygen concentration. CONCLUSION: The use of neonatal resuscitation self-inflating bags without reservoirs resulted in different delivered oxygen concentrations depending on gas flow rate, VR, PIP, and manufacturer, but not on lung compliance. This suggests that targeted oxygen concentrations could be delivered, even in lungs with decreased compliance, during resuscitation.


Assuntos
Oxigenoterapia/instrumentação , Oxigênio/administração & dosagem , Respiração com Pressão Positiva/instrumentação , Humanos , Técnicas In Vitro , Recém-Nascido , Complacência Pulmonar , Oxigenoterapia/métodos , Respiração com Pressão Positiva/métodos
5.
Tohoku J Exp Med ; 238(1): 65-74, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-26725844

RESUMO

Problem-based learning (PBL) is popular in medical education in Japan. We wished to understand the influence of PBL on the clinical competence of medical residents, using self-assessment and observer assessment. Tokyo Women's Medical University (TWMU) implemented PBL longitudinally (long-time) for four years, and on this basis we analyzed whether long-time PBL education is useful for clinical work. A self-assessment questionnaire was sent to junior and senior residents who were alumni of several schools, and an observation-based assessment questionnaire to senior doctors instructing them. Respondents were asked if they had used the PBL process in daily clinical tasks, and if so in what processes. Senior doctors were asked whether TWMU graduates perform differently from graduates of other schools. TWMU graduates answered "used a lot" and "used a little" with regard to PBL at significantly higher rates than other graduates. As useful points of PBL, they mentioned extracting clinical problems, solving clinical problems, self-directed leaning, positive attitude, collaboration with others, presentation, doctor-patient relations, self-assessment, and share the knowledge with doctors at lower levels and students. Observer assessments of TWMU graduates by senior doctors represented them as adaptive, good at presenting, good at listening to others' opinions, practical, selfish, and eager in their instructional practice. Longitudinal PBL can be a good educational method to develop lifelong-learning habits and clinical competencies especially in terms of the social aspect.


Assuntos
Competência Clínica , Educação de Graduação em Medicina , Hábitos , Aprendizagem Baseada em Problemas , Comportamento Social , Feminino , Humanos , Internato e Residência , Estudos Longitudinais , Masculino , Inquéritos e Questionários
6.
Clin Teach ; 11(5): 355-60, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25041668

RESUMO

BACKGROUND: It has been argued that the best method of acquiring clinical reasoning is through seeing new out-patients. The purpose of this interventional study was to establish a clinical clerkship course for Japanese medical students in an out-patient care setting, with multiple opportunities for reflective practice and improving the clinical reasoning abilities of the students. The effectiveness of the course was also examined. METHODS: Students performed examinations of new patients and made diagnostic decisions in 20 minutes. They presented their case using the SNAPPS (Summarize the case, Narrow the differential, Analyze the differential, Probe the preceptor, Plan management, and Select an issue for self directed learning) method, and this was followed by feedback from faculty members using the 1-minute preceptor method and a mini clinical evaluation exercise (mini-CEX). Students' clinical reasoning abilities were assessed by the objective structured clinical examination (OSCE) and the script concordance test (SCT). Students' written comments and responses to an interview about the course were also analysed. Cross-sectional data were examined by comparing individual OSCE and SCT scores, and the multiple-choice question examination (MCQ) completed by students who did and did not participate in this project. RESULTS: Students in the programme had higher scores on the mini-CEX in all areas. The SCT and OSCE scores were also significantly higher than the scores for the control group. Students' comments about the course, which provided an opportunity for daily reflection, were positive. DISCUSSION: Students rapidly acquired clinical reasoning skills through reflective practice. Students also demonstrated motivation to learn through the examination of new patients. The clinical clerkship programme with multiple opportunities for reflective practice in an out-patient care setting substantially improved the clinical reasoning abilities of medical students.


Assuntos
Assistência Ambulatorial , Estágio Clínico/métodos , Estágio Clínico/organização & administração , Competência Clínica , Avaliação Educacional , Retroalimentação , Humanos , Japão
7.
Tohoku J Exp Med ; 227(1): 23-9, 2012 05.
Artigo em Inglês | MEDLINE | ID: mdl-22516766

RESUMO

Acquiring clinical reasoning skills in lectures may be difficult, but it can be learnt through problem-solving in the context of clinical practice. Problem finding and solving are skills required for clinical reasoning; however, students who underwent problem-based learning (PBL) still have difficulty in acquiring clinical reasoning skills. We hypothesized that team-based learning (TBL), a learning strategy that provides the opportunity to solve problems by repeatedly taking tests, can enhance the clinical reasoning ability in medical students with PBL experiences during the pre-clinical years. TBL courses were designed for 4(th) year students in a 6-year program in 2008, 2009, and 2010. TBL individual scores, consisting of a combination of individual and group tests, were compared with scores of several examinations including computer-based testing (CBT), an original examination assessing clinical reasoning ability (problem-solving ability test; P-SAT), term examinations, and Objective Structured Clinical Examination (OSCE). CBT, OSCE and P-SAT scores were compared with those of students who learned clinical reasoning only through PBL tutorials in 2005, 2006, and 2007 (non-TBL students). Individual TBL scores of students did not correlate with scores of any other examination. Assessments on clinical reasoning ability, such as CBT, OSCE, and P-SAT scores, were significantly higher in TBL students compared with non-TBL students. Students found TBL to be effective, particularly in areas of problem solving by both individuals and teams, and feedback from specialists. In conclusion, TBL for clinical reasoning is useful in improving clinical reasoning ability in students with PBL experiences with limited clinical exposure.


Assuntos
Comportamento Cooperativo , Educação de Graduação em Medicina/métodos , Aprendizagem Baseada em Problemas/métodos , Avaliação de Programas e Projetos de Saúde , Ensino/métodos , Avaliação Educacional , Feminino , Humanos , Motivação , Aprendizagem Baseada em Problemas/estatística & dados numéricos , Faculdades de Medicina
8.
Endocr J ; 56(3): 391-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19225214

RESUMO

Painless thyroiditis is characterized by transient thyrotoxicosis with complete recovery. Some patients, however, have repeated episodes of thyrotoxicosis, for which the mechanism of recurrence is not clear. We therefore studied the clinical characteristics in 8 patients with 4 or more episodes of thyrotoxicosis and 40 control patients. The age at onset was significantly earlier and the male-to-female ratio was significantly higher in the case group than the control group. The highest FT4 and FT3 levels were higher in the recurrent type. Multiple regression analysis showed contributions of higher peak FT4 level, male gender, presence of thyroid autoantibody, earlier onset, and smaller size of thyroid to repeated recurrence. Since the peak FT4 value, gender, autoantibody, age of onset and size of thyroid contribute to only 27.5% of the repeated recurrence cases, other factors such as genetic susceptibility or inflammatory tissue changes in thyroid may also be contributory. Further studies are needed to elucidate the mechanism underlying repeated recurrence.


Assuntos
Tireoidite/diagnóstico , Adolescente , Adulto , Idade de Início , Autoanticorpos/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Regressão , Estudos Retrospectivos , Fatores Sexuais , Glândula Tireoide/imunologia , Glândula Tireoide/patologia , Tireoidite/sangue , Tireoidite/patologia , Tireotoxicose/diagnóstico , Tiroxina/sangue , Tri-Iodotironina/sangue
9.
Endocr J ; 56(2): 269-74, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19139594

RESUMO

The prevalence and titer of glutamic acid decarboxylase antibody (GADAb) in type 1 diabetes mellitus (T1DM) has been reported to be higher in patients with autoimmune thyroid diseases (AITD) than those without them. However, we have no data about the influence of GADAb on AITD. We therefore studied the clinical characteristics of Graves' disease (GD) with GADAb in order to clarify the influence of GADAb on GD. Twelve GD patients with GADAb were enrolled and were compared to 40 GD patients without DM. The male to female ratio and age of onset of GD showed no statistical difference. The titer of TSH receptor antibody (TRAb) at the onset of GD was similar in both groups. Initial treatment with methimazole (MMI) was started in all patients with GADAb but radioactive iodine (RI) therapy was carried out in five patients because of adverse effects of MMI or poor control of hyperthyroidism. The initial titer of TRAb was significantly lower in patients treated with MMI alone compared to that in RI treated patients but none of the patients treated with MMI alone went into remission after more than 3-years of follow up. We also compared these GADAb-positive patients with 14 patients with diabetes mellitus who had matched clinical features. The number of diabetic patients who remained in possible remission was significantly higher than that of GADAb-positive patients (5 in 14 vs 0 in 12). Moreover, the rate of remission in the diabetic patients was no different from that of 21 control patients without diabetes followed for more than 7 years (5 in 14 vs 7 in 21). These data suggested that GADAb-positive patients are unlikely to go into remission with antithyroid agents. Therefore, definitive therapies might be preferable for the initial treatment of GADAb-positive patients.


Assuntos
Antitireóideos/uso terapêutico , Glutamato Descarboxilase/imunologia , Doença de Graves/imunologia , Adulto , Idoso , Antitireóideos/imunologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/imunologia , Feminino , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Doença de Graves/radioterapia , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide/imunologia , Radioisótopos do Iodo/uso terapêutico , Masculino , Metimazol/uso terapêutico , Pessoa de Meia-Idade
11.
Intern Med ; 47(6): 515-20, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18344638

RESUMO

A 30-year-old normocalcemic man with hypopituitarism, hypogonadism, diabetes mellitus, and secondary hemochromatosis due to multiple blood transfusions was admitted because of adrenal crisis. After intravenous administration of saline and cortisol, the corrected serum level of calcium decreased to 7.3 mg/dl. This osteoporotic patient had been prescribed alendronate for radial bone fracture. Since the increase in intact PTH (68 pg/ml) was impaired compared to that seen in hypocalcemic patients with secondary hyperparathyroidism, we presume that the patient has had latent hypoparathyroidism, which was unmasked by the administration of glucocorticoid and bisphosphonate. With a supplemented dose of 1alpha-OHD3, the patient has been eucalcemic.


Assuntos
Alendronato/uso terapêutico , Doenças do Sistema Endócrino/metabolismo , Glucocorticoides/uso terapêutico , Hemocromatose/diagnóstico , Hipoparatireoidismo/diagnóstico , Osteoporose/tratamento farmacológico , Reação Transfusional , Glândulas Suprarrenais/metabolismo , Adulto , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/tratamento farmacológico , Cálcio/sangue , Diabetes Mellitus/metabolismo , Hemocromatose/etiologia , Humanos , Hipogonadismo/metabolismo , Hipoparatireoidismo/metabolismo , Hipopituitarismo/metabolismo , Masculino , Osteoporose/metabolismo , Hormônio Paratireóideo/sangue
12.
Biochem Genet ; 45(9-10): 713-24, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17876700

RESUMO

The single-strand conformation polymorphism (SSCP) procedure has been applied in routine testing for hereditary diseases. Temperature, running buffer, gel composition, and fragment length can influence its sensitivity. Mutation detection in the clinical setting depends on the development of automated technology, especially for large genes, such as the dihydropyrimidine dehydrogenase (DPYD) gene, which codes the initial, rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU). The authors have optimized the condition of SSCP with an automated system (GenePhor system, GE Healthcare UK Ltd.) to screen genetic polymorphisms in the DPYD gene. The efficiency of the method was evaluated using 21 positive controls (DNA samples with polymorphisms in the DPYD gene, previously characterized) and DNA samples from 35 Japanese. Results showed that the use of three different running buffers (pH 7.4, 8.3, and 9.0) in combination with other optimized conditions (10% polyacrylamide gel, 60-90 min at constant 900 V at 5 degrees C) resulted in a high polymorphism detection rate (95.3%), which was considered appropriate for routine screening. Therefore, this strategy could be useful for pharmacogenetic studies on 5FU.


Assuntos
Di-Hidrouracila Desidrogenase (NADP)/genética , Eletroforese em Gel de Poliacrilamida/métodos , Polimorfismo Conformacional de Fita Simples , Sequência de Bases , Primers do DNA/genética , Deficiência da Di-Hidropirimidina Desidrogenase/enzimologia , Deficiência da Di-Hidropirimidina Desidrogenase/genética , Eletroforese em Gel de Poliacrilamida/estatística & dados numéricos , Técnicas Genéticas/estatística & dados numéricos , Genética Populacional , Humanos , Japão , Mutagênese Sítio-Dirigida , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/estatística & dados numéricos , Sensibilidade e Especificidade
13.
Intern Med ; 46(9): 583-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17473494

RESUMO

A 19-year-old woman who had decreased eight centimeters in stature was diagnosed as Cushing's disease with multiple spine compression fractures. At the age of 18, the patient had a complex fracture and gradually presented the features of Cushing's syndrome. Her plasma ACTH and cortisol levels were extremely high. Radiological findings and chemical markers for bone metabolism showed severe osteoporosis. Magnetic resonance imaging showed the presence of a pituitary microadenoma. After transsphenoidal surgery was performed, subsequently all endocrine data improved. This case indicates that Cushing's syndrome should be considered for severe osteoporotic juvenile patients.


Assuntos
Achados Incidentais , Vértebras Lombares/lesões , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/diagnóstico , Fraturas da Coluna Vertebral/etiologia , Vértebras Torácicas/lesões , Absorciometria de Fóton , Adenoma/diagnóstico , Adenoma/cirurgia , Hormônio Adrenocorticotrópico/sangue , Adulto , Síndrome de Cushing/complicações , Síndrome de Cushing/diagnóstico , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/etiologia , Humanos , Hidrocortisona/sangue , Vértebras Lombares/diagnóstico por imagem , Imageamento por Ressonância Magnética , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Hipersecreção Hipofisária de ACTH/sangue , Neoplasias Hipofisárias/diagnóstico , Neoplasias Hipofisárias/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem
14.
Growth Horm IGF Res ; 16(4): 211-6, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16860583

RESUMO

In some patients with non-islet-cell tumor hypoglycemia (NICTH), a high molecular weight form of IGF-II (big IGF-II) derived from tumors is present in the circulation and might be associated with recurrent hypoglycemia. In this study, in order to survey the clinical characteristics of patients with IGF-II producing NICTH, we analyzed the medical records of 78 patients with NICTH (M/F 44/34, age 62+/-1.8, range; 9-86 years.) whose serum contained a large amount of big IGF-II. Hepatocellular carcinoma and gastric carcinoma were the most common causes of NICTH. The diameters of the tumors were more than 10 cm in 70% of the patients. Basal immunoreactive insulin (IRI) levels were less than 3 microU/dl in 79% of the patients. Hypoglycemic attack was the onset of disease in 31 of 65 cases (48%), but the tumor was revealed prior to the occurrence of hypoglycemia in 34 cases (52%). Twenty-five of 47 (53%) patients had decreased serum potassium levels. These data suggested that hypoinsulinemic hypoglycemia associated with the presence of a large tumor supports the diagnosis of IGF-II producing NICTH. Hypokalemia was associated with hypoglycemia in some patients. The BMI (21.4+/-0.6 kg/m2) and serum total protein levels (6.6+/-0.1g/dl) were preserved at the occurrence of first hypoglycemic attack suggesting that malnutrition might not be the main cause of hypoglycemia in most patients.


Assuntos
Hipoglicemia/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas/metabolismo , Adolescente , Neoplasias das Glândulas Suprarrenais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Neoplasias da Mama/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma de Células Renais/metabolismo , Criança , Feminino , Fibrossarcoma/metabolismo , Tumores do Estroma Gastrointestinal/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II , Leiomiossarcoma/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Feocromocitoma/metabolismo , Neoplasias da Próstata/metabolismo , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo
17.
Growth Horm IGF Res ; 14(6): 449-54, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15519253

RESUMO

Atherosclerosis and insulin resistance are common complications of adult growth hormone deficiency (GHD) and acromegaly. Circulating adiponectin, an adipocyte-derived protein, has both anti-atherogenic and insulin-sensitising effects. In this study, we measured serum adiponectin levels in patients with either adult GHD or acromegaly to clarify the impact of GH secretory states on the regulation of serum adiponectin levels. Serum adiponectin level was measured by radioimmunoassay in 32 patients with adult GHD, 49 patients with acromegaly and 25 normal subjects. The relationships between adiponectin and insulin sensitivity index assessed as quantitative insulin sensitivity check index (QUICKI), BMI, and serum GH and IGF-I levels were then investigated. The values of QUICKI were significantly lower in patients with acromegaly or adult GHD compared to normal subjects (0.33 +/- 0.03, P < 0.01, 0.35 +/- 0.04, P < 0.05 and 0.36 +/- 0.01, respectively). While patients with adult GHD had significantly lower serum adiponectin levels than patients with acromegaly (6.5 +/- 3.9, 9.2 +/- 5.0, P < 0.01) these levels were not significantly different from those found in normal subjects (7.8 +/- 4.3 mug/ml). There was an inverse correlation between serum adiponectin levels and BMI in both patient groups (GHD r = -0.39, P < 0.05; Acromegaly r = -0.35, P < 0.05). However, serum adiponectin levels correlated positively with QUICKI (R(s) = 0.37, P < 0.05) only in patients with adult GHD. In patients with acromegaly, the levels of circulating adiponectin showed an inverse correlation with serum IGF-I levels (R(s) = -0.34, P < 0.05), but not with basal GH levels. These results demonstrate that adiponectin levels are significantly lower in patients with adult GHD than in patients with acromegaly. Adiponectin levels are similar in patients with GHD and healthy controls, whereas in patients with acromegaly, insulin resistance appears to be not closely related to adiponectin levels compared with BMI. The different relationship between adiponectin and QUICKI observed in the adult GHD and acromegaly groups presumably reflects differences in the mechanisms of insulin resistance under states of GH deficiency or excess.


Assuntos
Acromegalia/sangue , Hormônio do Crescimento Humano/deficiência , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Adiponectina , Adulto , Idoso , Índice de Massa Corporal , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Resistência à Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade , Valores de Referência
18.
Biol Neonate ; 86(3): 176-82, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15237241

RESUMO

The purpose of this study was to test the effectiveness of a new Doppler index combining systolic and diastolic time intervals (the Tei index) in the prospective assessment of ventricular function and pulmonary circulation in a newborn piglet model with hypoxic pulmonary hypertension during inhaled nitric oxide (NO). Piglets were prepared for the experiments under normal air, hypoxia, and hypoxia-with-inhaled-NO conditions. Complete two-dimensional Doppler echocardiographic examinations were performed in each condition. The right-ventricle (RV) Tei index increased with hypoxia and decreased following the inhalation of NO. Furthermore, there was a direct correlation between the individual changes in the RV Tei index and individual changes in mean pulmonary arterial pressure in each condition. We conclude that the Tei index is useful for assessing cardiac function and pulmonary circulation in hypoxic pulmonary hypertension during inhaled NO. These results suggest that the Tei index provides an objective assessment of persistent pulmonary hypertension of the newborn.


Assuntos
Animais Recém-Nascidos , Coração/fisiologia , Hipóxia/tratamento farmacológico , Pulmão/fisiologia , Óxido Nítrico/administração & dosagem , Ultrassonografia Doppler em Cores , Animais , Dióxido de Carbono/sangue , Diástole , Concentração de Íons de Hidrogênio , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Pulmão/irrigação sanguínea , Oxigênio/sangue , Reprodutibilidade dos Testes , Suínos , Sístole , Fatores de Tempo , Função Ventricular Esquerda , Função Ventricular Direita
19.
J Clin Endocrinol Metab ; 88(12): 5981-8, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14671200

RESUMO

The type 1 IGF receptor (IGF1R) is required for normal embryonic and postnatal growth. The aim of this study was to determine whether we could detect abnormal IGF1R function in skin fibroblasts from children with an abnormal copy number of the IGF1R gene. We report two children with altered copy number of the IGF1R gene who presented with abnormal growth. Case 1 is a girl with intrauterine growth retardation, postnatal growth failure, and recurrent hypoglycemia. Pituitary function tests were normal. Routine karyotype analysis identified a deletion on 15q26.2, and a fluorescence in situ hybridization study using IGF1R probes showed only a single IGF1R gene. Case 2 was large for gestational age, with birth weight and length at or above 97th percentile, and showed rapid early postnatal growth. He was found to have a recombinant chromosome 15 containing a partial duplication at 15q (q25-qter). A fluorescence in situ hybridization study using the same probes showed three copies of the IGF1R gene. In a mitochondrial activity assay, skin fibroblasts from the subject with only one copy of IGF1R showed slower growth, whereas cells from the subject with three copies of IGF1R showed accelerated growth compared with controls. IGF1R phosphorylation, as assessed by Western blot, and IGF1R binding studies were decreased compared with controls in the child with one copy of the IGF1R and increased in the child with three copies of the gene. Our data are consistent with the concept that IGF1R gene copy number is of functional and clinical importance in humans.


Assuntos
Fibroblastos/patologia , Dosagem de Genes , Transtornos do Crescimento/genética , Transtornos do Crescimento/patologia , Receptor IGF Tipo 1/genética , Pele/patologia , Estatura , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Criança , Pré-Escolar , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Cinética , Masculino , Fosforilação , Receptor IGF Tipo 1/metabolismo , Proteínas Recombinantes/farmacologia , Tirosina/metabolismo
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