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1.
Eur J Gastroenterol Hepatol ; 36(7): 890-896, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829943

RESUMO

OBJECTIVE: Short-chain fatty acids (SCFAs) are produced when the microbiota in the large intestine cause fermentation of dietary carbohydrates and fibers. These fatty acids constitute the primary energy source of colon mucosa cells and have a protective effect in patients suffering from inflammatory bowel disease (IBD). This study aimed to compare the SCFA levels in the stools of patients with IBD and healthy controls. METHOD: Healthy controls and patients with IBD aged 18 and over were included in the study. Stool samples from all patients and healthy controls were collected, and stool acetic acid, propionic acid, and butyric acid levels were measured using a gas chromatography-mass spectrometry measurement method. RESULTS: In this study, 64 participants were divided into two groups: 34 were in IBD (Crohn disease and ulcerative colitis) and 30 were in healthy control group. When fecal SCFA concentrations of IBD and healthy control groups were compared, a statistically significant difference was observed between them. When the fecal SCFA concentrations of Crohn's disease and ulcerative colitis patients in the IBD group were compared, however, no statistically significant difference was observed between them. Furthermore, when the participants' diet type (carbohydrate-based, vegetable-protein-based and mixed diet) and the number of meals were compared with fecal SCFA concentrations, no statistically significant difference was observed between them. CONCLUSION: In general, fecal SCFA levels in patients with IBD were lower than those in healthy controls. Moreover, diet type and the number of meals had no effect on stool SCFA levels in patients with IBD and healthy individuals.


Assuntos
Colite Ulcerativa , Doença de Crohn , Ácidos Graxos Voláteis , Fezes , Humanos , Fezes/química , Fezes/microbiologia , Masculino , Feminino , Adulto , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/metabolismo , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Doença de Crohn/metabolismo , Adulto Jovem , Cromatografia Gasosa-Espectrometria de Massas , Dieta , Propionatos/metabolismo , Propionatos/análise , Ácido Acético/análise , Ácido Acético/metabolismo , Microbioma Gastrointestinal , Ácido Butírico/análise , Ácido Butírico/metabolismo
2.
Cancer Cell ; 42(4): 568-582.e11, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38490213

RESUMO

Major histocompatibility complex (MHC) class I antigen presentation deficiency is a common cancer immune escape mechanism, but the mechanistic implications and potential strategies to address this challenge remain poorly understood. Studying ß2-microglobulin (B2M) deficient mouse tumor models, we find that MHC class I loss leads to a substantial immune desertification of the tumor microenvironment (TME) and broad resistance to immune-, chemo-, and radiotherapy. We show that treatment with long-lasting mRNA-encoded interleukin-2 (IL-2) restores an immune cell infiltrated, IFNγ-promoted, highly proinflammatory TME signature, and when combined with a tumor-targeting monoclonal antibody (mAB), can overcome therapeutic resistance. Unexpectedly, the effectiveness of this treatment is driven by IFNγ-releasing CD8+ T cells that recognize neoantigens cross-presented by TME-resident activated macrophages. These macrophages acquire augmented antigen presentation proficiency and other M1-phenotype-associated features under IL-2 treatment. Our findings highlight the importance of restoring neoantigen-specific immune responses in the treatment of cancers with MHC class I deficiencies.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Animais , Camundongos , Antígenos de Histocompatibilidade Classe I/genética , Interleucina-2/genética , Interleucina-2/imunologia , Neoplasias/genética , RNA Mensageiro , Microambiente Tumoral
3.
J Cardiothorac Vasc Anesth ; 37(1): 65-72, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36307353

RESUMO

OBJECTIVE: The authors aimed to compare the anti-inflammatory and antioxidant effects of propofol and sevoflurane in children with cyanotic congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blind study. SETTING: Single center, university hospital. PARTICIPANTS: Children ages 1-10 years with CCHD undergoing elective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Children were randomized to receive general anesthesia with either sevoflurane (group S) or propofol (group P). Systemic inflammatory response syndrome (SIRS) occurrence was assessed at the end of the surgery and at the sixth, 12th, and 24th postoperative hours. Blood samples were obtained at 4 times: after anesthesia induction (T0), after release of the aortic cross-clamp (T1), at the end of the surgery (T2), and at the postoperative 24th hour (T3). The serum levels of interleukin 6 and tumor necrosis factor alpha, and the total antioxidant status (TAS) and total oxidant status, were analyzed. RESULTS: SIRS was more common in group S than in group P at all times (p = 0.020, p = 0.036, p = 0.004, p = 0.008). There were no significant differences between the groups in the mean tumor necrosis factor alpha and interleukin 6 levels at any time. The TAS level at T2 was higher in group P than group S (p = 0.036). The serum TAS level increased at T2 compared with T0 in group P, but it decreased in group S (p = 0.041). CONCLUSION: The results showed that propofol provided a greater antioxidant effect and reduced SIRS postoperatively more than sevoflurane in children with CCHD undergoing cardiac surgery.


Assuntos
Anti-Inflamatórios , Antioxidantes , Cardiopatias Congênitas , Propofol , Sevoflurano , Criança , Pré-Escolar , Humanos , Lactente , Anestésicos Inalatórios/uso terapêutico , Anestésicos Intravenosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cianose , Cardiopatias Congênitas/cirurgia , Interleucina-6 , Propofol/uso terapêutico , Estudos Prospectivos , Sevoflurano/uso terapêutico , Síndrome de Resposta Inflamatória Sistêmica , Fator de Necrose Tumoral alfa
4.
Indian J Psychiatry ; 64(3): 257-263, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35859547

RESUMO

Background: Vitamin D has been found to be associated with the pathogenesis of attention deficit hyperactivity disorder (ADHD). However, the potential role of parathyroid hormone (PTH) is still unclear. Aim: We aimed to investigate the association between calcium metabolism and ADHD symptomatology. Methods: We included 106 participants aged between 7 and 13 years old (51 ADHD patients, mean age: 9.54 ± 1.77, 55 healthy controls mean age: 9.97 ± 0.94) to this study. K-SADS-PL and Conners' Parent/Teacher Rating Scales, Stroop Test were performed. Blood samples to measure serum levels of Vitamin D, PTH, calcium (Ca), magnesium (Mg), phosphorus (P), and alkaline phosphatase (ALP) were collected in the spring (March-April-May) to prevent seasonal variability. Results: PTH, P, and ALP values were significantly lower and Vitamin D, Ca, and Mg values were significantly higher in the ADHD group (P < 0.05, for all). Both groups had Vitamin D deficiency. Control group has lower Vitamin D levels than the ADHD group (respectively; 17.66 ± 9.07, 21.99 ± 10.99, P < 0.05). There was a negative correlation between PTH and CTRS hyperactivity, CGI-RI and CGI-EL sub-scores, CGI-Total, DSM-IV-Inattention, DSM-IV Hyperactivity/Impulsivity, DSM-IV-Total scores (P < 0.05, for all). Conclusions: We found lower PTH levels in ADHD patients and a strong and negative correlation between PTH and symptom severity. Future studies are needed to clarify if these findings are due to the key role of PTH in ADHD pathology or PTH's function in activating vitamin D.

5.
Med Princ Pract ; 31(6): 532-539, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35537400

RESUMO

OBJECTIVE: Neuroblastoma is a common fatal tumor of childhood. Natural killer (NK) cells can exert direct cytotoxicity on tumor cells. The killer immunoglobulin-like receptor (KIR) family of NK cell receptors is involved in activation/inhibition of NK cells. In the KIR gene cluster, six of them (3DS1, 2DS1-5) encode receptors triggering activation, while seven of them (3DL1-3, 2DL1-3, 2DL5) encode receptors triggering inhibition. We aimed to assess the distribution of genetic polymorphisms of KIRs on the clinical course of neuroblastoma and provide guidance on potential therapeutic options. METHODS: Our study group included 50 neuroblastoma patients and 100 healthy children as controls. Twenty-eight patients were boys, and twenty-two were girls; median age was 36 months. Fourteen patients had stage 1, 2, 3, or 4S disease, and 36 patients had stage 4 disease. Isolated DNA from the peripheral blood was amplified for sequence-specific oligonucleotide probe analysis of 16 KIR genes. The Fisher's exact test was used to evaluate the variation of KIR gene distribution. RESULTS: All patients had a lower frequency of KIR2DS3 compared to the control group (p = 0.005). Evaluation of individual KIR genes/genotypes in patients with early stages (stage 1, 2, 3, and 4S) versus stage 4 disease revealed that the frequency of KIR2DS3 was increased in early stages (p = 0.023). Inhibitory KIR2DL3 was increased in the patient group compared to controls (p = 0.038). Furthermore, the frequency of KIR2DL3 was higher in stage 4 neuroblastoma patients compared to the patients with early stages (p = 0.023). CONCLUSION: Our data suggest a role for KIR2DS3 and KIR2DL3 in development of neuroblastoma. Thus, modulation of KIR2SD3 and/or KIR2DL3 expression or function might present a novel therapeutic strategy for neuroblastoma.


Assuntos
Neuroblastoma , Receptores KIR , Masculino , Feminino , Criança , Humanos , Pré-Escolar , Receptores KIR/genética , Receptores KIR/metabolismo , Genótipo , Polimorfismo Genético/genética , Células Matadoras Naturais/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Frequência do Gene , Receptores KIR2DL3/genética , Receptores KIR2DL3/metabolismo
8.
J Gynecol Obstet Hum Reprod ; 50(10): 102223, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34509694

RESUMO

PURPOSE: There is evidence that follicular phase progesterone rise [FPPR] adversely affects fresh in vitro fertilization [IVF] cycles. A single daily dose of cetrorelix has been used to prevent early luteinizing Hormone (LH) surge. We speculated that doubling the daily dose might have a positive effect in patients who have early LH surges despite receiving the single daily dose treatment. However, a double daily dose of cetrorelix seems to cause FPPR in poor ovarian response (POR) patients. MATERIALS AND METHODS: On human chorionic gonadotropin [hCG] injection days, the progesterone levels of POR patients who received a single daily dose of cetrorelix (group 1, n = 59) were compared with progesterone levels of the patients who received a double daily dose of cetrorelix (group 2, n = 75). The two groups had statistically similar demographic data. The patients who had FPPR were detected, and a comparison of progesterone levels, using 0.8, 1.0, and 1.2 [ng/mL] of progesterone as cut-off levels, was made between patients of both groups. RESULTS: FPPR patients in group 2 had significantly higher progesterone levels during hCG day, contrary to expectations. When progesterone cut-off levels of 0.8, 1.0, and 1.2 [ng/mL] were used for group 1 patients, 15.3%, 13.6%, and 6.8% of the patients developed FPPR, respectively When the progesterone cut-off levels of 0.8, 1.0, and 1.2 [ng/mL] were used for group 2, the results detected were 45.3%, 30.7%, and 21.3%, respectively. A significant statistical difference in progesterone levels was observed between the groups. CONCLUSION: While the double daily dose of cetrorelix was initially thought to more effectively suppress early LH rise by some authors, we have seen that it increases the FPPR more when compared to a single daily dose regime. We suggest using frozen cycles instead of fresh cycles in order to have better endometrial receptivity in patients who seem to benefit from higher daily doses of cetrorelix.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Indução da Ovulação/normas , Progesterona/análise , Fase Folicular/efeitos dos fármacos , Fase Folicular/metabolismo , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Indução da Ovulação/métodos , Indução da Ovulação/estatística & dados numéricos , Progesterona/sangue , Estatísticas não Paramétricas
9.
Int J Mol Sci ; 22(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299215

RESUMO

Synchronous primary malignancies occur in a small proportion of head and neck squamous cell carcinoma (HNSCC) patients. Here, we analysed three synchronous primaries and a recurrence from one patient by comparing the genomic and transcriptomic profiles among the tumour samples and determining the recurrence origin. We found remarkable levels of heterogeneity among the primary tumours, and through the patterns of shared mutations, we traced the origin of the recurrence. Interestingly, the patient carried germline variants that might have predisposed him to carcinogenesis, together with a history of alcohol and tobacco consumption. The mutational signature analysis confirmed the impact of alcohol exposure, with Signature 16 present in all tumour samples. Characterisation of immune cell infiltration highlighted an immunosuppressive environment in all samples, which exceeded the potential activity of T cells. Studies such as the one described here have important clinical value and contribute to personalised treatment decisions for patients with synchronous primaries and matched recurrences.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Mutação , Recidiva Local de Neoplasia/genética , Neoplasias Primárias Múltiplas/genética , Idoso , Consumo de Bebidas Alcoólicas/genética , Evolução Fatal , Perfilação da Expressão Gênica , Genômica , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Fumantes/estatística & dados numéricos
10.
Science ; 371(6525): 145-153, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33414215

RESUMO

The ability to control autoreactive T cells without inducing systemic immune suppression is the major goal for treatment of autoimmune diseases. The key challenge is the safe and efficient delivery of pharmaceutically well-defined antigens in a noninflammatory context. Here, we show that systemic delivery of nanoparticle-formulated 1 methylpseudouridine-modified messenger RNA (m1Ψ mRNA) coding for disease-related autoantigens results in antigen presentation on splenic CD11c+ antigen-presenting cells in the absence of costimulatory signals. In several mouse models of multiple sclerosis, the disease is suppressed by treatment with such m1Ψ mRNA. The treatment effect is associated with a reduction of effector T cells and the development of regulatory T cell (Treg cell) populations. Notably, these Treg cells execute strong bystander immunosuppression and thus improve disease induced by cognate and noncognate autoantigens.


Assuntos
Efeito Espectador/imunologia , Encefalomielite Autoimune Experimental/terapia , Terapia de Imunossupressão/métodos , Esclerose Múltipla/terapia , Vacinas Sintéticas/uso terapêutico , Animais , Células Apresentadoras de Antígenos , Autoantígenos/genética , Inflamação/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Pseudouridina/análogos & derivados , Pseudouridina/química , RNA Mensageiro/efeitos adversos , RNA Mensageiro/química , RNA Mensageiro/genética , Linfócitos T Reguladores/imunologia , Vacinas Sintéticas/efeitos adversos , Vacinas de mRNA
11.
Biochem Med (Zagreb) ; 31(1): 010705, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33380892

RESUMO

INTRODUCTION: To interpret test results correctly, understanding of the variations that affect test results is essential. The aim of this study is: 1) to evaluate the clinicians' knowledge and opinion concerning biological variation (BV), and 2) to investigate if clinicians use BV in the interpretation of test results. MATERIALS AND METHODS: This study uses a questionnaire comprising open-ended and close-ended questions. Questions were selected from the real-life numerical examples of interpretation of test results, the knowledge about main sources of variations in laboratories and the opinion of clinicians on BV. A total of 399 clinicians were interviewed, and the answers were evaluated using a scoring system ranked from A (clinician has the highest level of knowledge and the ability of using BV data) to D (clinician has no knowledge about variations in laboratory). The results were presented as number (N) and percentage (%). RESULTS: Altogether, 60.4% of clinicians have knowledge of pre-analytical and analytical variations; but only 3.5% of them have knowledge related to BV. The number of clinicians using BV data or reference change value (RCV) to interpret measurements results was zero, while 79.4% of clinicians accepted that the difference between two measurements results located within the reference interval may be significant. CONCLUSIONS: Clinicians do not use BV data or tools derived from BV such as RCV to interpret test results. It is recommended that BV should be included in the medical school curriculum, and clinicians should be encouraged to use BV data for safe and valid interpretation of test results.


Assuntos
Técnicas de Laboratório Clínico , Ciência de Laboratório Médico , Humanos , Valores de Referência , Reprodutibilidade dos Testes
12.
Turk Neurosurg ; 29(4): 570-575, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30984996

RESUMO

AIM: To assess the distribution of genetic polymorphisms of killer cell immunoglobulin-like receptors (KIRs) to predict the clinical course of glioblastoma, report on the genetic mechanisms, and provide guidance on potential therapeutic methods. MATERIAL AND METHODS: Our study included 31 adult patients who were admitted to the Department of Neurosurgery at our institution and diagnosed with glioblastoma between October 2013 and January 2014 together with 50 control subjects. RESULTS: The mean age of the patients was 53.5 vs. 53.9 years, respectively, and the gender distribution (male/female: 64.5/35.5% vs. 64/36%, respectively) was comparable among patients and controls (p > 0.05). Sixteen different KIR genes including inhibitory, activating, and pseudogenes were investigated for each sample, and the framework genes including KIR2DL4, 3DL2, 3DL3, and 3DP1 were present in all patients and controls. In addition, the inhibitory KIR genes and the 2DL3 gene were significantly more common in patients compared to controls (p < 0.05). CONCLUSION: This study demonstrated that the inhibitory KIR gene 2DL3 has a predisposition for glioblastoma. Identifying the potential link between glioblastoma cells and immune system genetics is critical in predicting familial predisposition and early diagnosis. In addition, this clue may be a key factor in developing post-surgery individual immunotherapy models in the future.


Assuntos
Neoplasias Encefálicas/genética , Glioblastoma/genética , Polimorfismo Genético/genética , Receptores KIR/genética , Adulto , Neoplasias Encefálicas/diagnóstico , Feminino , Frequência do Gene/genética , Genótipo , Glioblastoma/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
13.
Ther Adv Musculoskelet Dis ; 11: 1759720X19832321, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854031

RESUMO

BACKGROUND: The aim of this study was to assess the serum chitotriosidase (ChT) and neopterin levels in patients with ankylosing spondylitis (AS) and to evaluate whether serum ChT and neopterin levels are related to disease activity. METHODS: A total of 86 patients with AS were included in the study. Patients were divided into two groups based on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores: The active AS patients group included 40 patients who had a BASDAI score ⩾4. The inactive AS patients group included 46 patients who had a BASDAI score <4. We compared the serum level of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), ChT and neopterin between the two groups. RESULTS: Active AS patients had significantly higher ESR, CRP, serum ChT and neopterin levels compared with the inactive AS patients group (p < 0.05). Positive correlations were found between serum ChT levels and ESR (r = 0.87, p = 0.005), and CRP levels (r = 0.86, p = 0.006). Also, there was a positive significant correlation between serum ChT levels and BASDAI scores (r = 0.67, p = 0.03). No correlation was found between serum neopterin levels and the BASDAI scores, ESR, and CRP levels (p > 0.05). Higher disease activity (BASDAI score ⩾4) was found to be associated with ChT (p = 0.012) in the multiple logistic regression analysis. CONCLUSION: The present study emphasized that serum ChT levels can be useful in the determination of the disease activity of AS patients.

14.
J Cell Biochem ; 120(8): 12091-12100, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30912190

RESUMO

Entry of ß-elemene into various phases of clinical trials advocates its significance as a premium candidate likely to gain access to mainstream medicine. Based on the insights gleaned from decades of research, it seems increasingly transparent that ß-elemene has shown significant ability to modulate multiple cell signaling pathways in different cancers. We partition this multicomponent review into how ß-elemene strategically modulates various signal transduction cascades. We have individually summarized regulation of tumor necrosis factor related apoptosis-inducing ligand, signal transducers and activators of transcription, transforming growth factor/SMAD, NOTCH, and mammalian target of rapamycin pathways by ß-elemene. Last, we will discuss the results of clinical trials of ß-elemene and how effectively we can use these findings to stratify patients who can benefit most from ß-elemene.


Assuntos
Progressão da Doença , Neoplasias/metabolismo , Neoplasias/patologia , Sesquiterpenos/farmacologia , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Ensaios Clínicos como Assunto , Humanos , Metástase Neoplásica , Neoplasias/genética , Transdução de Sinais/efeitos dos fármacos
15.
Adv Clin Exp Med ; 28(3): 291-297, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29969202

RESUMO

BACKGROUND: Recent reports have indicated an improved prognosis in sepsis with ß-blocker agents; however, the underlying action mechanism is still under debate. OBJECTIVES: The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats. MATERIAL AND METHODS: The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation. RESULTS: Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells. CONCLUSIONS: These results suggest that the improved outcome with ß-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of ß-blockers on the endothelium may lead to a better understanding of sepsis.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Propranolol/uso terapêutico , Sepse/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Lesão Pulmonar Aguda/patologia , Animais , Modelos Animais de Doenças , Ligadura , Pulmão/patologia , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos
16.
Sarcoidosis Vasc Diffuse Lung Dis ; 36(4): 285-293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32476964

RESUMO

BACKGROUND: Impaired systolic function is common in sarcoidosis however the frequency of diastolic dysfunction (DD) and it's possible genetic basis has not been fully elucidated yet. The aim of this study is to evaluate the frequency of left ventricular DD(LVDD) and right ventricular DD(RVDD) and it's possible relationship between Human Leukocyte Antigen(HLA)-DRB1* alleles in patients with sarcoidosis. METHODS: Seventy seven patients (51 females, mean age 41.1±8.2yrs) without known sarcoid related or any other structured heart disease and 77 healthy controls with a similar age and gender (38.7±7.8yrs,51 females) were included in the case control study. DD was diagnosed with echocardiography. RVDD was defined as early(E)/late(A) ratio<1 or >2 on tricuspit valve. LVDD was defined as E/A ratio<1 or >2 on mitral valve, with isovolumetric relaxation time(IVRT)>90 miliseconds(msn) or deceleration rate of early diastolic flow(Edec)>220msn respectively. All patients were HLAtyped with the Sequence Specific Oligonucleotide Probe(SSOP) method. RESULTS: The frequencies of LVDDs and RVDDs were significantly higher in sarcoidosis patients than the controls (26.0% vs. 2.6% for LVDD; and 42.9% vs. 18.2% for RVDD)(p<0.05). No significant difference was found in patients according to the presence of RVDD and LVDD in terms of age, gender or respiratory function test parameters. Although the frequency of HLA DRB1* alleles were comparable among patients with RVDD, HLA DRB1*14 alleles were more frequent in patients with LVDD. CONCLUSIONS: Biventricular DD is common in patients with sarcoidosis without manifest cardiac involvement. HLA DRB1*14 allele seems to be related with LVDD in this study population.


Assuntos
Cadeias HLA-DRB1/genética , Sarcoidose Pulmonar/complicações , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Direita/etiologia , Função Ventricular Esquerda/genética , Função Ventricular Direita/genética , Adulto , Estudos de Casos e Controles , Diástole , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/genética , Sarcoidose Pulmonar/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/genética , Disfunção Ventricular Direita/fisiopatologia
17.
J Clin Lab Anal ; 32(1)2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28205271

RESUMO

BACKGROUND: Organizing work flow is a major task of laboratory management. Recently, clinical laboratories have started to adopt methodologies such as Lean Six Sigma and some successful implementations have been reported. This study used Lean Six Sigma to simplify the laboratory work process and decrease the turnaround time by eliminating non-value-adding steps. METHODS: The five-stage Six Sigma system known as define, measure, analyze, improve, and control (DMAIC) is used to identify and solve problems. The laboratory turnaround time for individual tests, total delay time in the sample reception area, and percentage of steps involving risks of medical errors and biological hazards in the overall process are measured. RESULTS: The pre-analytical process in the reception area was improved by eliminating 3 h and 22.5 min of non-value-adding work. Turnaround time also improved for stat samples from 68 to 59 min after applying Lean. Steps prone to medical errors and posing potential biological hazards to receptionists were reduced from 30% to 3%. CONCLUSION: Successful implementation of Lean Six Sigma significantly improved all of the selected performance metrics. This quality-improvement methodology has the potential to significantly improve clinical laboratories.


Assuntos
Serviços de Laboratório Clínico , Melhoria de Qualidade , Gestão da Qualidade Total , Serviços de Laboratório Clínico/organização & administração , Serviços de Laboratório Clínico/normas , Serviços de Laboratório Clínico/estatística & dados numéricos , Erros de Diagnóstico/prevenção & controle , Humanos , Fatores de Tempo , Fluxo de Trabalho
18.
Sarcoidosis Vasc Diffuse Lung Dis ; 35(3): 184-191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-32476901

RESUMO

Background: A wide range of HLA-DR alleles have been associated with sarcoidosis either in terms of disease phenotype or extra pulmonary involvement, however the effect on non-resolution in different ethnic groups is not fully understood. The aim of this study was to investigate whether disease characterics and HLA-DRB1 alleles may early reflect non resolution in sarcoidosis. Methods: 91 patients who were diagnosed in Cukurova University Faculty of Medicine Department of Chest Diseases between 1993-2012 and were followed up until June 2017 were included in the study. All patients underwent HLA analysis by the Sequence Specific Oligonucleotide Prob (SSOP) method. Fifteen of them were excluded from the study group due to lost of follow-up (n=6) and not yet passed 5 years since diagnosis (n=9). Complete resolution at 5th year was defined according to the predefined standard criteria (ACCESS). Results: The resolution rate was 51.3%. The HLA-DRB1*14 allele was significantly higher in patients without resolution (11.8 vs 1.3%)(p=0.006). According to multivariate logistic regression analysis the independent risk factors of non resolution were female gender (OR: 12.6; 95%CI: 2.1-74.9, p=0.005), HLA DRB1*14 allele (OR:51.9; 95%CI: 3.6-735.8, p=0.000), baseline TLCO<75%(predicted) (OR:3.8; 95%CI: 1.1-13.7, p=0.028), extra-pulmonary involvement (OR:3.7; 95%CI: 1.0-13.1, p=0.038) and advanced stage at baseline (OR: 8.3; 95%CI: 1.9-35.4, p=0.001). Conclusions: HLA-DRB1*14 alleles, lower baseline TLCO, advanced stage, female gender or the presence of extra-pulmonary involvement could predict long term non-resolution in sarcoidosis. Early prediction of long term prognosis may affect treatment decisions and avoid further deterioration in these patient groups. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 184-191).

19.
Turk Kardiyol Dern Ars ; 45(8): 731-738, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29226894

RESUMO

OBJECTIVE: Familial hypercholesterolemia (FH) is a life-threatening genetic disease associated with elevated low-density lipoprotein cholesterol (LDL-C) and premature coronary heart disease that is undiagnosed and undertreated around the world. This study aimed to examine the demographic characteristics, awareness, and treatment adherence of undiagnosed or undertreated FH patients based on laboratory records. METHODS: In a 16-month retrospective survey using laboratory records, patients with elevated LDL-C (>250 mg/dL) were identified (n=395). Patients younger than 18 years of age or with secondary causes of dyslipidemia were excluded (n=98). In all, 297 patients were called and asked to participate in a phone interview regarding their demographic characteristics, awareness of dyslipidemia, and treatment adherence. RESULTS: A total of 147 patients (mean age: 51.7±16.6 years; 59.2% female) completed the interview. The mean LDL-C level of the patients was 292.8±49.9 mg/dL. According to the Dutch Lipid Clinic Network criteria, 18.4% of the patients had definite FH, 66.0% had probable FH, and 15.6% had possible FH. Although the majority of the patients (93.9%) were aware of their high LDL-C level, only about half of them (n=75; 51.0%) were in treatment. Of all the patients who were interviewed, 21% (n=31) had never taken medication to lower their LDL-C, and 28% (n=41) had stopped taking a lipid-lowering drug. CONCLUSION: This pilot study revealed that a significant number of FH patients were not taking statins despite having a very high LDL-C level. Nationwide detection of likely FH patients using hospital records and interviewing them via a phone survey may help to better understand and manage these high-risk patients.


Assuntos
Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/epidemiologia , Adulto , Idoso , LDL-Colesterol/sangue , Diagnóstico Tardio , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Inquéritos e Questionários , Centros de Atenção Terciária
20.
Turk J Obstet Gynecol ; 14(3): 176-180, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29085708

RESUMO

OBJECTIVE: Anemia in the first trimester of pregnancy is the situation as described by the World Health Organization when the level of hemoglobin (Hb) is less than 11 g in 100 cc of blood. The prevalence of this problem is 18% in developed countries, whereas it is between 35-75% in developing countries. In this study, we aimed to determine the prevalence of anemia at the time of pregnancy detection. MATERIALS AND METHODS: A retrospective cross-sectional study was designed to determine the prevalence of anemia. A total of 5228 first trimester pregnant women were admitted to the study between 2012 and 2014. Hb levels of 11 to 9.5 g/dL, 9.5 to 8 g/dL, and less than 8 g/dL were considered as mild, moderate, and severe anemia, respectively. RESULTS: We detected mild, modarate, and severe anemia at rates of 16.64%, 3.07%, and 0.28%, respectively, in our population. The overall prevalence of anemia at the time of detection of pregnancy was 20.0%. CONCLUSION: Anemia is a significant risk factor for maternal mortality in developing countries. The prevalence of anemia at the time of pregnancy detection was 20% and this rate is close to those indicated in developed countries.

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