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Benefits of breastfeeding for both the mother and the child are well established, but a comprehensive and robust study to investigate the protective effect of breastfeeding and attenuated time effect stratified by cause of morbidity are lacking. This study is based on the nationwide birth cohort in Korea that includes data on all infants born from 2009 to 2015. Of 1,608,540 children, the median follow-up period was 8.41 years (interquartile range, 6.76-10.06). When compared to children with fully formula feeding, the hospital admission rate was 12% lower in those with partially breastfeeding and 15% lower in those with exclusive breastfeeding. The apparent protective effect of breastfeeding was reduced with increasing age. Our study provides potential evidence of the beneficial association of breastfeeding on subsequent hospital admissions. The protective effect declined over time as the children grew older. Encouraging any breastfeeding for at least the first 6 months among infants is an important public health strategy to improve overall child health.
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Coorte de Nascimento , Aleitamento Materno , Criança , Lactente , Feminino , Humanos , República da Coreia/epidemiologia , Saúde da Criança , HospitaisRESUMO
BACKGROUND: There is limited comprehensive evidence on the potential association between early menarche and subsequent health outcomes. AIM: To evaluate the existing evidence for the association of early menarche with later health outcomes and assesse the strength and validity of the evidence for these associations. DESIGN: Umbrella review. METHODS: We searched PubMed, Web of Science, Embase, CINAHL, Cochrane Database of Systematic Reviews and Google Scholar, and manually screened retrieved references to find systematic reviews and meta-analyses from inception to July 2021. Early menarche was defined by taking into account ethnicity and birth year, and the outcomes were long-term consequences in adulthood. RESULTS: Thirteen reviews encompassing 283 original articles and over 6.8 million participants from 39 countries across 5 continents were included. In categorical outcomes, early menarche was associated with metabolic syndrome (n = 37 543 pooled adjusted relative risk [aRR] 1.56, 95% confidence interval (CI) 1.33, 1.83; high certainty [Hi]), endometrial cancer (n = 874 188, aRR 1.40, 95% CI 1.17, 1.68; Hi), type 2 diabetes mellitus/impaired glucose tolerance (n = 1 185 444, aRR 1.30, 95% CI 1.19, 1.42; Hi), breast cancer (n = 103 574, aRR 1.19, 95% CI 1.06, 1.33; Hi), death from all causes (n = 152 747, aRR 1.11, 95% CI 1.03, 1.19; Hi), obesity (n = 54 006, aRR 1.68, 95% CI 1.53, 1.84; moderate certainty [Mod]), gestational diabetes mellitus (n = 48 535, aRR 1.32, 95% CI 1.09, 1.58; Mod), hypertension (n = 1 682 689, aRR 1.24, 95% CI 1.20, 1.29; Mod), endometriosis (n = 885 390, aRR 1.22, 95% CI 1.09, 1.37; Mod), ovarian cancer (n = 1 022 451, aRR 1.17, 95% CI 1.04, 1.31; Mod) and asthma (n = 22 859, aRR 1.31, 95% CI 1.09, 1.57; low certainty [Lo]). For continuous outcomes, early menarche was associated with increased body mass index (BMI) in adults ≥40 years of age (n = 121 943, adjusted pooled standardized mean difference [aSMD] 0.30, 95% CI 0.28, 0.32; Mod), BMI in adults <40 years of age (n = 124 728, aSMD 0.39, 95% CI 0.36, 0.43; Mod), serum fasting insulin level (n = 17 020, aSMD 0.52, 95% CI 0.48, 0.57; Mod) and homeostatic model assessment of insulin resistance (n = 7925, aSMD 0.27, 95% CI 0.19, 0.35; Mod). CONCLUSION: We found varied levels of evidence for the association between early menarche and the development of subsequent health problems. Our results recommend that physicians should pay attention to these associations, as early menarche can be a potential indicator of metabolic disorders and female-specific cancer and cause death in women.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Hipertensão , Gravidez , Adulto , Feminino , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Revisões Sistemáticas como Assunto , Avaliação de Resultados em Cuidados de SaúdeRESUMO
PURPOSE: The effects of circadian blood pressure (BP) alterations on the development and progression of microvascular complications in type 1 diabetes mellitus (T1DM) patients are unknown. We evaluated the effects of circadian BP alterations with development of microvascular complications during follow-up with patients with childhood-onset T1DM. METHODS: We investigated the medical records of 81 pediatric patients with T1DM who underwent 24-hour ambulatory BP monitoring (ABPM) between January 2009 and February 2010. RESULTS: Mean age at diagnosis and ABPM evaluation was 8.0±3.9 and 15.6±2.4 years, respectively. Hypertension (daytime, nighttime, and 24-hour mean hypertension) data were available in 42 patients. During the 8 years of follow-up after ABPM, microvascular complications occurred in 8 patients (diabetic retinopathy [DR] alone in 5, microalbuminuria alone in 2, and both in 1), of whom 7 had nondipper BP. Nighttime diastolic BP, nighttime mean arterial pressure, and glycated hemoglobin A (HbA1c) level were higher in patients with DR than in those without DR (P<0.05 for all). Daytime or nighttime BP and presence of dipper BP were not related to microvascular complications, but diabetic microvascular complications were more likely to occur in patients with an older age at diagnosis and higher HbA1c level. The proportion of patients with DR was higher in those with nondipper hypertension (83.3%) compared with dipper and nondipper normotension (0% and 16.7%, respectively; P=0.021). CONCLUSION: As a predictor of microvascular complications, nondipper hypertension was not significant. Glycemic control rather than nondipper hypertension is the predominant factor determining DR in T1DM patients.
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Childhood-onset polyarteritis nodosa (PAN) is a rare and systemic necrotising vasculitis in children affecting small- to medium-sized arteries. To date, there have been only a few reports because of its rarity. Thus, we aimed to investigate the clinical manifestations, laboratory findings, treatment, and long-term outcomes in patients with childhood-onset PAN and to evaluate the usefulness of the paediatric vasculitis activity score (PVAS). We retrospectively analysed the data of nine patients with childhood-onset PAN from March 2003 to February 2020. The median ages at symptom onset, diagnosis, and follow-up duration were 7.6 (3-17.5), 7.7 (3.5-17.6), and 7.0 (1.6-16.3) years, respectively. All patients had constitutional symptoms and skin manifestations, while five exhibited Raynaud's phenomenon. Organ involvement was observed in one patient. The median PVAS at diagnosis was 7 (range: 2-32). Prednisolone was initially used for induction in all patients, and other drugs were added in cases refractory to prednisolone. All patients survived, but three patients with high PVAS at diagnosis experienced irreversible sequelae, including intracranial haemorrhage and digital amputation. In conclusion, early diagnosis and treatment may minimise sequelae in patients with childhood-onset PAN. This study suggests that high PVAS score at diagnosis may be associated with poor prognosis.
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Poliarterite Nodosa/patologia , Vasculite/patologia , Adolescente , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Masculino , Poliarterite Nodosa/epidemiologia , Poliarterite Nodosa/cirurgia , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Vasculite/epidemiologia , Vasculite/cirurgiaRESUMO
Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver cancer affecting adolescents and young adults without any pre existing liver disease. Hyperammonemic encephalopathy (HAE) is a serious paraneoplastic syndrome, and several cases of HAE have been reported in patients with FLHCC. This condition is rare; hence, there are currently no management guidelines for cancer-related HAE. Herein, we report a case of an 18-year-old man with advanced FLHCC who developed HAE during the first course of chemotherapy consisting of cisplatin, doxorubicin, 5-fluorouracil, and interferon-α. He was successfully treated with continuous venovenous hemofiltration, sodium benzoate, sodium phenylbutyrate, and amino acid supplementation for HAE. After the second course of chemotherapy, he underwent surgery, and thereafter, his ammonia levels were normal without any ammonia scavenger therapy. Treatments for HAE described here will be helpful for this rare, but serious metabolic complication of FLHCC and could partially applied to HAE related to any malignancies.
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Amônia/uso terapêutico , Encefalopatias/etiologia , Carcinoma Hepatocelular/complicações , Neoplasias Hepáticas/complicações , Doença da Deficiência de Ornitina Carbomoiltransferase/complicações , Adolescente , Encefalopatias/fisiopatologia , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , MasculinoRESUMO
BACKGROUND: The short-stature homeobox-containing gene (SHOX) is one of the major growth genes in humans. The clinical spectrum of SHOX haploinsufficiency ranges from Léri-Weill dyschondrosteosis to idiopathic short stature. Herein, we describe the clinical and genetic characteristics of 23 Korean patients with SHOX deficiency disorders. METHODS: Medical records of 23 patients (19 females and 4 males) from 15 unrelated families who were genetically confirmed to have SHOX deficiency were retrospectively reviewed. SHOX gene deletions or mutations were determined by sequence analyses using multiplex ligation-dependent probe amplification, chromosomal microarray, and/or Sanger sequencing methods. RESULTS: In the 15 families, 9 probands were de novo cases. All 23 patients showed mesomelia. Madelung deformity and tibia vara were observed in 13 (56.5%) and 3 (13.1%) patients, respectively. Genetically, 11 (73.3%) of the 15 families showed SHOX deletions of various sizes, and the other 4 families harboured SHOX sequence variants. Four patients had undergone orthopaedic surgeries (3 for tibia vara and 1 for Madelung deformity). Among 7 patients who had received growth hormone treatment for ≥1 year, 5 showed good responses, with a median first-year change-in-height standard deviation score of +0.6. There were no significant differences in the clinical characteristics of the deletion and point mutation groups. CONCLUSIONS: A high index of suspicion and the genetic confirmation of SHOX deficiency are helpful for the timely management of the condition and are needed to provide genetic counselling to the family members of the patients.
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Nanismo/genética , Transtornos do Crescimento/genética , Haploinsuficiência/genética , Deformidades Congênitas dos Membros/genética , Osteocondrodisplasias/genética , Proteína de Homoeobox de Baixa Estatura/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , República da Coreia , Estudos RetrospectivosRESUMO
PURPOSE: Adverse drug events (ADEs) are associated with high health and financial costs and have increased as more elderly patients treated with multiple medications emerge in an aging society. It has thus become challenging for physicians to identify drugs causing adverse events. This study proposes a novel approach that can improve clinical decision making with recommendations on ADE causative drugs based on patient information, drug information, and previous ADE cases. MATERIALS AND METHODS: We introduce a personalized and learning approach for detecting drugs with a specific adverse event, where recommendations tailored to each patient are generated using data mining techniques. Recommendations could be improved by learning the associations of patients and ADEs as more ADE cases are accumulated through iterations. After consulting the system-generated recommendations, a physician can alter prescriptions accordingly and report feedback, enabling the system to evolve with actual causal relationships. RESULTS: A prototype system is developed using ADE cases reported over 1.5 years and recommendations obtained from decision tree analysis are validated by physicians. Two representative cases demonstrate that the personalized recommendations could contribute to more prompt and accurate responses to ADEs. CONCLUSION: The current system where the information of individual drugs exists but is not organized in such a way that facilitates the extraction of relevant information together can be complemented with the proposed approach to enhance the treatment of patients with ADEs. Our illustrative results show the promise of the proposed system and further studies are expected to validate its performance with quantitative measures.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Mineração de Dados , Técnicas de Apoio para a Decisão , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , MédicosRESUMO
The CAG repeat length of the androgen receptor (AR) gene, which exhibits an inverse relationship to AR sensitivity, might influence the development of the pubarche along with hyperandrogenemia. There are ethnic differences in the AR CAG repeat length, however, no Asian studies on premature pubarche (PP) have been reported, including Korea. Our objectives were to examine the hormone levels and AR CAG repeat length, and to assess their contributions to PP in Korean girls. Subjects with PP (n=16) and normal pubarche (NP, n=16), and normal controls (NC, n=16) were enrolled. The levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and free testosterone (FT) were checked. The methylation-weighted (MW) average CAG repeat lengths were analyzed. The median ages at pubarche were 7.4 and 8.9 years in the PP and NP groups, respectively, and the levels of 17-OHP, DHEAS, and FT were similar in both groups. The PP group exhibited a higher DHEAS:DHEA ratio than the NP group (P=0.014). The medians of the MW average CAG repeat length of the AR gene were 22.4 for all subjects and did not differ among the PP (22.3), NP (22.4), and NC (22.2) groups. The AR CAG repeat lengths in the PP and NP groups did not correlate with DHEAS or FT levels. These results suggest that the AR CAG repeat length was not involved in the development of PP in Korean girls. However, excessive adrenal androgen levels, particularly those caused by increased sulfotransferase activity, might be important in the pathogenesis of PP.
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Androgênios/sangue , Puberdade Precoce/sangue , Puberdade Precoce/genética , Receptores Androgênicos/genética , Repetições de Trinucleotídeos/genética , Estudos de Casos e Controles , Criança , Feminino , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/genética , Resistência à Insulina , Polimorfismo Genético , República da CoreiaRESUMO
BACKGROUND: This study investigated the clinical manifestations of lower extremity edema (LEE) in locally advanced cervical cancer patients treated with two different strategies. METHODS: In total, 79 cervical cancer survivors with International Federation of Gynecology and Obstetrics stage IB2-IIB were included. Six survivors with stage IB1 and who had been suspicious for lymph node metastasis on pretreatment image also were included. Forty-two patients received radiotherapy after pretreatment laparoscopic surgical staging (Group 1), and 43 patients received primary radiotherapy (Group 2). The patients' medical records and survey results of the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) were analyzed. RESULTS: The incidence of LEE was higher in Group 1 than in Group 2 (69.0 vs. 11.6 %; P < 0.001). The duration of LEE was longer in Group 1 (mean 77.3 vs. 9.4 months). At the time of survey, 47.6 % of the patients in Group 1 were clinically diagnosed with lymphedema compared with no patients in Group 2. In GCLQ-K, the mean symptom cluster scores for general swelling (0.74 vs. 0.09; P < 0.001), limb swelling (0.22 vs. 0.00; P = 0.006), and heaviness (0.45 vs. 0.23; P = 0.033) were significantly higher in Group 1. One patient in Group 1 developed lymphedema-related angiosarcoma that was diagnosed at 7.8 years after surgery. CONCLUSIONS: Patients with cervical cancer who underwent radiotherapy after laparoscopic surgical staging more commonly experienced LEE and related symptoms than patients who underwent primary radiotherapy. As LEE decreases patients' quality of life, it should be considered during patient consultation and surveillance.
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Laparoscopia , Extremidade Inferior/patologia , Linfedema/epidemiologia , Radioterapia/efeitos adversos , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adulto , Idoso , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/radioterapia , Carcinoma Adenoescamoso/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Incidência , Linfedema/diagnóstico , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgia , Adulto JovemRESUMO
PURPOSE: The goal of this study was to investigate clinical manifestations of lower extremity edema (LEE) after lymph node dissection in patients with primary endometrial cancer. METHODS: Women with primary endometrial cancer who underwent staging surgery between November 2001 and March 2011 were included in the study. Medical records and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were used for LEE evaluation. RESULTS: All 154 patients underwent pelvic lymph node dissection, and 126 patients (81.8 %) underwent paraaortic LN dissection. The median age of the patients was 52 years, the majority had stage I cancer (78.6 %), and most had endometrioid histology (90.9 %). The most frequent GCLQ responses were "experienced swelling" (35.7 %), "experienced numbness" (30.5 %), "experienced heaviness" (29.9 %), and "experienced aching" (29.9 %). Sixty-four patients (41.6 %) had previous (9/64, 14.1 %) and/or current (55/64, 85.9 %) patient-reported LEE. Most patients developed LEE within 12 months after surgery (39/56, 69.6 %), and LEE lasted for more than 12 months in most patients (45/56, 80.4 %). Three patients reported recurrent LEE after recovery. Multivariate logistic regression identified the number of dissected pelvic lymph node (≥21) as a risk factor for LEE [odds ratio (OR) 3.28; 95 % confidence interval (CI) 1.058-10.136] and postoperative radiotherapy (OR 3.81, 95 % CI 1.67-8.69). CONCLUSIONS: LEE developed in more than one-third of patients with endometrial cancer after surgery, and LEE lasted for more than 12 months in most patients. A high number of dissected pelvic lymph nodes and postoperative radiotherapy is associated with LEE.
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Adenocarcinoma de Células Claras/cirurgia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias do Endométrio/cirurgia , Extremidade Inferior/patologia , Excisão de Linfonodo/efeitos adversos , Linfedema/epidemiologia , Complicações Pós-Operatórias , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Incidência , Linfedema/diagnóstico , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , República da Coreia/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVE: We investigated whether the frequency, phenotype, and suppressive function of CD4+ FOXP3+ regulatory T cells (Tregs) are altered in young TS patients with the 45,X karyotype compared to age-matched controls. DESIGN AND METHODS: Peripheral blood mononuclear cells from young TS patients (n = 24, 17.4-35.9 years) and healthy controls (n = 16) were stained with various Treg markers to characterize their phenotypes. Based on the presence of thyroid autoimmunity, patients were categorized into TS (-) (n = 7) and TS (+) (n = 17). Tregs sorted for CD4+ CD25bright were co-cultured with autologous CD4+ CD25- target cells in the presence of anti-CD3 and -CD28 antibodies to assess their suppressive function. RESULTS: Despite a lower frequency of CD4+ T cells in the TS (-) and TS (+) patients (mean 30.8% and 31.7%, vs. 41.2%; P = 0.003 and P < 0.001, respectively), both groups exhibited a higher frequency of FOXP3+ Tregs among CD4+ T cells compared with controls (means 1.99% and 2.05%, vs. 1.33%; P = 0.029 and P = 0.004, respectively). There were no differences in the expression of CTLA-4 and the frequency of Tregs expressing CXCR3+, and CCR4+ CCR6+ among the three groups. However, the ability of Tregs to suppress the in vitro proliferation of autologous CD4+ CD25- T cells was significantly impaired in the TS (-) and TS (+) patients compared to controls (P = 0.003 and P = 0.041). Meanwhile, both the TS (-) and TS (+) groups had lower frequencies of naïve cells (P = 0.001 for both) but higher frequencies of effector memory cells (P = 0.004 and P = 0.002) than did the healthy control group. CONCLUSIONS: The Tregs of the TS patients could not efficiently suppress the proliferation of autologous effector T cells, despite their increased frequency in peripheral CD4+ T cells.
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Proliferação de Células/fisiologia , Ativação Linfocitária/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Síndrome de Turner/imunologia , Adulto , Antígenos CD4/metabolismo , Antígeno CTLA-4/metabolismo , Células Cultivadas , Técnicas de Cocultura , Citometria de Fluxo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunofenotipagem , Adulto JovemRESUMO
OBJECTIVE: To evaluate the impact of lower limb lymphedema (LLL) on quality of life (QOL) in cervical, ovarian, and endometrial cancer survivors after pelvic lymph node dissection. STUDY DESIGN: A cross-sectional case-control study was performed using the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). In total, 25 women with LLL and 28 women without LLL completed both questionnaires. RESULTS: The GCLQ-K total symptom score and scores for swelling-general, swelling-limb, and heaviness were significantly higher in the LLL group than in the control group. In the EORTC QLQ-C30, the LLL group reported more financial difficulties compared to the control group (mean score, 16.0 vs. 6.0; P=0.035). Global health status was poorer in the LLL group with borderline statistical significance (mean score, 62.7 vs. 71.4; P=0.069). Spearman's correlations suggested that global health status in the EORTC QLQ-C30 correlated with the GCLQ-K total symptom score (in the LLL group, R=-0.64, P=0.001; in the control group, R=-0.42, P=0.027). CONCLUSIONS: QOL decreases due to LLL-related symptoms and financial difficulty in women with LLL. Well-designed prospective studies are required to confirm these findings.
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Neoplasias dos Genitais Femininos/cirurgia , Excisão de Linfonodo/efeitos adversos , Linfedema/psicologia , Qualidade de Vida , Sobreviventes/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Extremidade Inferior , Linfedema/economia , Linfedema/etiologia , Pessoa de Meia-Idade , Pelve , Projetos Piloto , República da Coreia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The objective of this study was to investigate clinical manifestations of lower extremity edema (LEE) in early ovarian cancer. METHODS: Patients with early ovarian cancer who underwent staging surgery between January 2001 and December 2010. Medical records for LEE and/or responses to the Gynecologic Cancer Lymphedema Questionnaire (GCLQ) were evaluated. RESULTS: Patients had a median age of 46 years. Twenty-nine patients (40.8%) had past (13 patients, 44.8%) and/or current patient-reported LEE (16 patients, 55.2%). Symptoms reported on the GCLQ in over 20% of respondents were numbness, firmness/tightness, swelling, heaviness, limited movement of knee, and aching. GCLQ total symptoms score was significantly higher in patients with current LEE. Most of the LEE (25/29, 86.2%) developed within 12 months after surgery and LEE lasted more than 6 months in approximately two-thirds of the patients (18/29, 62.1%). Only half of the patients (52.1%) indicated knowledge of lymphedema: 86.2% of LEE patients and 28.6% of patients with no LEE. CONCLUSIONS: Although a significant proportion of patients with ovarian cancer have LEE after surgery, most are not aware of lymphedema until they develop. Education and analyses for LEE and lymphedema are needed in patients with ovarian cancer.
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Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Extremidade Inferior/patologia , Linfedema/epidemiologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Carcinoma Epitelial do Ovário , Estudos Transversais , Feminino , Humanos , Incidência , Linfedema/diagnóstico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Prevalência , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: The purpose of this study was two-fold: first, to develop a Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) and evaluate its reliability and reproducibility and second, to examine the diagnostic efficacy of GCLQ-K in predicting lymphedema in gynecologic cancer survivors. METHODS: We designed a case-control study, and the GCLQ-K was completed by 33 gynecologic cancer survivors with lymphedema and 34 gynecologic cancer survivors without lymphedema. A follow-up GCLQ-K was completed 3weeks after the baseline questionnaire. RESULTS: The GCLQ-K showed high reliability with a Cronbach's α of 0.83 and high reproducibility with an intraclass correlation of 0.96. Of the 7 symptom clusters, 6 identified patients with lymphedema with statistical significance; identification of lymphedema using the physical functioning and infection-related symptom clusters did not reach significance. The area under the receiver operating characteristic curve (AUC) to distinguish patients with and without lymphedema was 0.868 (95% confidence interval [CI], 0.779-0.956). Following the exclusion of the physical functioning and infection-related symptom clusters, which showed poor prediction value for lymphedema, the AUC of the GCLQ-K total score further improved to 0.922 (95% CI, 0.864-0.981). CONCLUSION: The GCLQ-K was successfully developed with minimal modifications to adapt the original GCLQ to the Korean culture and showed high internal consistency and reproducibility. Moreover, gynecologic cancer survivors with and without lymphedema could be satisfactorily distinguished using the GCLQ-K. Thus, GCLQ-K was proven to be a reliable tool, capable of identifying lymphedema in Korean gynecological cancer survivors.
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Neoplasias do Endométrio/cirurgia , Linfedema/diagnóstico , Neoplasias Ovarianas/cirurgia , Inquéritos e Questionários , Neoplasias do Colo do Útero/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Características Culturais , Feminino , Humanos , Idioma , Excisão de Linfonodo/efeitos adversos , Linfedema/etiologia , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Aggregation of misfolded protein and resultant intracellular inclusion body formation are common hallmarks of mutant superoxide dismutase (mSOD1)-linked familial amyotrophic lateral sclerosis (FALS) and have been associated with the selective neuronal death. Protein disulfide isomerase (PDI) represents a family of enzymatic chaperones that can fold nascent and aberrant proteins in the endoplasmic reticulum (ER) lumen. Recently, our group found that S-nitrosylated PDI could contribute to protein misfolding and subsequent neuronal cell death. However, the exact role of PDI in the pathogenesis of ALS remains unclear. In this study, we propose that PDI attenuates aggregation of mutant/misfolded SOD1 and resultant neurotoxicity associated with ER stress. ER stress resulting in PDI dysfunction therefore provides a mechanistic link between deficits in molecular chaperones, accumulation of misfolded proteins, and neuronal death in neurodegenerative diseases. In contrast, S-nitrosylation of PDI inhibits its activity, increases mSOD1 aggregation, and increases neuronal cell death. Specifically, our data show that S-nitrosylation abrogates PDI-mediated attenuation of neuronal cell death triggered by thapsigargin. Biotin switch assays demonstrate S-nitrosylated PDI both in the spinal cords of SOD1 (G93A) mice and human patients with sporadic ALS. Therefore, denitrosylation of PDI may have therapeutic implications. Taken together, our results suggest a novel strategy involving PDI as a therapy to prevent mSOD1 aggregation and neuronal degeneration. Moreover, the data demonstrate that inactivation of PDI by S-nitrosylation occurs in both mSOD1-linked and sporadic forms of ALS in humans as well as mice.
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Esclerose Lateral Amiotrófica/enzimologia , Mutação/fisiologia , Neurônios/enzimologia , Isomerases de Dissulfetos de Proteínas/biossíntese , Superóxido Dismutase/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Animais , Morte Celular/fisiologia , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Transgênicos , Neurônios/patologia , Superóxido Dismutase/genética , Superóxido Dismutase-1RESUMO
BACKGROUND: Patients with ALS may be exposed to variable degrees of chronic intermittent hypoxia. However, all previous experimental studies on the effects of hypoxia in ALS have only used a sustained hypoxia model and it is possible that chronic intermittent hypoxia exerts effects via a different molecular mechanism from that of sustained hypoxia. No study has yet shown that hypoxia (either chronic intermittent or sustained) can affect the loss of motor neurons or cognitive function in an in vivo model of ALS. OBJECTIVE: To evaluate the effects of chronic intermittent hypoxia on motor and cognitive function in ALS mice. METHODS: Sixteen ALS mice and 16 wild-type mice were divided into 2 groups and subjected to either chronic intermittent hypoxia or normoxia for 2 weeks. The effects of chronic intermittent hypoxia on ALS mice were evaluated using the rotarod, Y-maze, and wire-hanging tests. In addition, numbers of motor neurons in the ventral horn of the spinal cord were counted and western blot analyses were performed for markers of oxidative stress and inflammatory pathway activation. RESULTS: Compared to ALS mice kept in normoxic conditions, ALS mice that experienced chronic intermittent hypoxia had poorer motor learning on the rotarod test, poorer spatial memory on the Y-maze test, shorter wire hanging time, and fewer motor neurons in the ventral spinal cord. Compared to ALS-normoxic and wild-type mice, ALS mice that experienced chronic intermittent hypoxia had higher levels of oxidative stress and inflammation. CONCLUSIONS: Chronic intermittent hypoxia can aggravate motor neuronal death, neuromuscular weakness, and probably cognitive dysfunction in ALS mice. The generation of oxidative stress with activation of inflammatory pathways may be associated with this mechanism. Our study will provide insight into the association of hypoxia with disease progression, and in turn, the rationale for an early non-invasive ventilation treatment in patients with ALS.
Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Hipóxia/metabolismo , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Esclerose Lateral Amiotrófica/fisiopatologia , Animais , Modelos Animais de Doenças , Feminino , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Força Muscular , Estresse Oxidativo , Desempenho Psicomotor , Teste de Desempenho do Rota-Rod , Transdução de SinaisRESUMO
Cu/Zn-superoxide dismutase (SOD1) is present in the cytosol, nucleus, peroxisomes and mitochondrial intermembrane space of human cells. More than 114 variants of human SOD1 have been linked to familial amyotrophic lateral sclerosis (ALS), which is also known as Lou Gehrig's disease. Although the ultimate mechanisms underlying SOD1-mediated cytotoxicity are largely unknown, SOD1 aggregates have been strongly implicated as a common feature in ALS. This study examined the mechanism for the formation of SOD1 aggregates in vitro as well as the nature of its cytotoxicity. The aggregation propensity of SOD1 species was investigated using techniques ranging from circular dichroism spectroscopy to fluorescence dye binding methods, as well as electron microscopic imaging. The aggregation of SOD1 appears to be related to its structural instability. The demetallated (apo)-SOD1 and aggregated SOD1 species, with structurally disordered regions, readily undergo aggregation in the presence of lipid molecules, whereas metallated (holo)-SOD1 does not. The majority of aggregated SOD1s that are induced by lipid molecules have an amorphous morphology and exhibit significant cytotoxicity. The lipid binding propensity of SOD1 was found to be closely related to the changes in surface hydrophobicity of the proteins, even at very low levels, which induced further binding and assembly with lipid molecules. These findings suggest that lipid molecules induce SOD1 aggregation under physiological conditions and exert cytotoxicity, and might provide a possible mechanism for the pathogenesis of ALS.
Assuntos
Lipídeos/química , Conformação Proteica , Superóxido Dismutase/química , Esclerose Lateral Amiotrófica/enzimologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Lipídeos/farmacologia , Microscopia Eletrônica de Transmissão , Células PC12 , Ratos , Espectrometria de Fluorescência , Superóxido Dismutase/farmacologia , Superóxido Dismutase/ultraestruturaRESUMO
BACKGROUND: 'Retinoid dermatitis' is a retinoid-induced irritant contact dermatitis (ICD). The mechanism of retinoid dermatitis may be different from that of other ICDs. However, it remains uncertain how topical retinoid induce ICD. OBJECTIVE: We compared several aspects of contact dermatitis induced by topical retinol and benzalkonium chloride (BKC) on hairless mice skin. METHODS: 2% retinol or 2.5% BKC was applied to hairless mice and transepidermal water loss (TEWL), ear thickness, histologic and immunohistochemical findings were compared. We also compared mRNA expression of inflammatory cytokines, epidermal differential markers, cyclooxygenases (COXs) and heparin binding epidermal growth factor like growth factor (HB-EGF). RESULTS: Topical application of 2% retinol and 2.5% BKC increased TEWL and ear thickness in similar intensity. Epidermal hyperplasia was more prominent in retinol treated skin. Proliferating cell nuclear antigen, involucrin and loricrin expression were higher in retinol-treated skin than in BKC-treated skin. Filaggrin, however, was more expressed in BKC-treated skin. The mRNA expression of IL-8, TNF-alpha, COX-2, involucrin, loricrin and filaggrin were increased in both retinol- and BKC-treated skin in similar intensity. HB-EGF was more significantly increased in retinol-treated skin. CONCLUSION: Elevated HB-EGF and epidermal hyperplasia are more prominent features of retinoid dermatitis than in BKC-induced ICD.
RESUMO
BACKGROUNDS: Epidermolysis bullosa simplex (EBS) is a group of hereditary bullous disorders caused by mutations in the keratin genes KRT5 and KRT14. A significant genotype-phenotype correlation has been noted in previous studies of EBS. OBJECTIVE: In order to identify additional EBS mutations and elucidate the genotype-phenotype correlations in Korean EBS patients, we performed the first large scale mutational analysis of EBS patients of Korean origin. METHODS: We investigated fifteen Korean EBS patients by performing a sequence analysis of the entire coding sequences of KRT5 and KRT14. RESULTS: We identified six novel mutations, four within KRT5 (p.V143F, p.R265P, p.C479X and p.Asn177del), and two within KRT14 (p.R125L and p.L401P). In all, 13 missense, 1 nonsense, and 1 small deletion mutation were found. Five mutations in Dowling-Meara type (K14-p.R125H, K14-p.R125L, K5-E477K, K5-p.C479X and K5-p.Asn177del) were located in the highly conserved ends of the alpha-helical rod domain, the helix initiation (HIP), or helix termination (HTP) peptides of KRT5 and KRT14. Further, seven and three mutations were identified in EBS-generalized type and EBS-localized type, respectively. The positions of the mutations in both subtypes were more widely distributed within the rod domains and in the L12 linker domains of both keratin genes. CONCLUSIONS: This study should provide useful data and enhance our understanding of the EBS genotype-phenotype relationship. The genotype-phenotype correlation in Korean EBS patients was similar to previous studies performed in other ethnic groups. Lastly, our results confirmed that the mutational location in KRT5 or KRT14 is the most important factor in determining the phenotype severity.