RESUMO
Often transfusions red blood cells in patients with hereditary anemias lead to iron overload, that can cause endocrine complications, such as growth retardation, hypothyroidism, hypogonadism, and disorders of carbohydrate metabolism.Clinical case 1. A boy with transfusion-dependent (TD) Diamond-Blackfan anemia at 16.3 years presented with impaired fasting glucose, growth hormone (GH) deficiency, hypogonadotropic hypogonadism; GH therapy was initiated. At the age of 16.8 years old secondary hypothyroidism, secondary hypocorticism and diabetes mellitus were diagnosed. At 17.2 years continuous glucose monitoring (CGM) detected glucose elevations up to 11.7 mmol/l. Therapy with GH and testosterone ethers was continued; levothyroxine and cortef were stopped by patient. At 17.9 years height was 163 cm; no data supporting hypothyroidism nor hypocorticism; glycaemia within goal range.Clinical case 2. A girl with TD beta-thalassemia major at the age of 11.5 years presented with GH deficiency; GH therapy has been conducted from 12.8 to 15.3 years of age. At 13.8 years retardation of pubertal development was diagnosed. At 15.0 hyperglycemia 7.2 mmol/l was detected; normal results of oral glucose tolerance test (OGTT) were observed; glycemia elevations were up to 9.5 mmol/l according to CGM data. At 16.0 height was 152 cm; because of pubertal development arrest hormone replacement therapy was prescribed.CONCLUSION. Growth, pubertal and carbohydrate metabolism disorders were diagnosed in patients with TD hereditary anemias, that confirms the necessity of regularly endocrine investigation. To detect impairment of carbohydrate metabolism investigation of fasting blood glucose, OGTT, and CGM is recommended; glycated hemoglobin measurement is not considered reasonable.
Assuntos
Anemia , Diabetes Mellitus , Nanismo Hipofisário , Hipogonadismo , Hipopituitarismo , Hipotireoidismo , Adolescente , Criança , Feminino , Humanos , Masculino , Anemia/complicações , Glicemia/metabolismo , Automonitorização da Glicemia , Nanismo Hipofisário/complicações , Hipotireoidismo/etiologiaRESUMO
BACKGROUND: Diagnostics of growth hormone deficiency (GHD) and secondary adrenal insufficiency (SAI) is based on estimation of peak GH and cortisol concentrations in provocation tests. Russian consensus on diagnostics and treatment of hypopituitarism in children and adolescences recommends to measure GH and cortisol concentrations in every time-point of insulin test (IT). Glucagon test (GT) is discussed in literature as alternative to IT. AIMS: To estimate the possibility to use provocation GT for diagnostics of SAI and GHD in children and adolescents. MATERIALS AND METHODS: We investigated blood and urine cortisol levels, IT, and GT in 20 patients 6.5-17.8 years (Me 13.0 (10.4; 15.3)) after surgery and/or radiology and/or chemical therapy of head and neck tumors; remission for 0.4-7.5 years (Ðе 2.1 (1.5; 5.2)). RESULTS: With cut-off point 550 nmol/L sensitivity and specifity of IT was 100% and 60%, GT - 100% and 53% respectively. Minimal cortisol cut-off level for GT with sensitivity 100% was 500 nmol/L, maximal with specifity 100% - 400 nmol/L.Early morning cortisol levels did not exceed 250 nmol/l in 2 patients with SAI; and were above 500 nmol/l in 8 patients without SAI while primary or repeated examination.GHD was reviled by IT in all patients. Maximal GH concentrations in GT and IT did not differ significantly (p>0.05) but GT results of 4 patients exceeded or met cut-off for this test (7 ng/ml).GT was characterized by less severity compared with IT. CONCLUSIONS: For diagnostics of SAI by GT we can advise cut-off points of cortisol level 500 (sensitivity 100%, specifty 53%) and 400 nmol/L (sensitivity 80%, specifity 100%). Measuring of cortisol levels in 2-3 early morning blood samples allows to exclude or to suspect SAI in half of patients before tests. GH peaks in GT can exceed similarly data in IT that needs future investigation.
Assuntos
Insuficiência Adrenal , Hipopituitarismo , Adolescente , Insuficiência Adrenal/diagnóstico , Criança , Glucagon , Hormônio do Crescimento , Humanos , Hipopituitarismo/diagnóstico , InsulinaRESUMO
Circulating cell-free DNA (cfDNA) is one of the fastest growing and most exciting areas in oncology in recent years. Its potential clinical uses cover now each phase of cancer patient management care (predictive information, detection of the minimal residual disease, early detection of resistance, treatment monitoring, recurrence surveillance, and cancer early detection/screening). This review relates the recent advances in the application of circulating DNA or RNA in oncology building on unpublished or initial findings/work presented at the 10th international symposium on circulating nucleic acids in plasma and serum held in Montpellier from the 20th to the 22nd of September 2017. This year, presenters revealed their latest data and crucial observations notably in relation to (i) the circulating cell-free (cfDNA) structure and implications regarding their optimal detection; (ii) their role in the metastatic or immunological processes; (iii) evaluation of miRNA panels for cancer patient follow up; (iv) the detection of the minimal residual disease; (v) the evaluation of a screening tests for cancer using cfDNA analysis; and (vi) elements of preanalytical guidelines. This work reviews the recent progresses in the field brought to light in the meeting, as well as in the most important reports from the literature, past and present. It proposes a broader picture of the basic research and its potential, and of the implementation and current challenges in the use of circulating nucleic acids in oncology.
Assuntos
Biomarcadores Tumorais/sangue , Ácidos Nucleicos Livres/sangue , DNA de Neoplasias/sangue , Neoplasias/sangue , Detecção Precoce de Câncer , Humanos , Biópsia Líquida , MicroRNAs/sangue , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/sangue , Neoplasia Residual/patologia , Neoplasias/genética , Neoplasias/patologiaRESUMO
In an attempt to better understand potential biomarkers for, and the role of macrophages in, the development of atherosclerosis, the toxicologic, and any therapeutic pharmacologic effects of carboxymethylated ß-glucan, gadolinium chloride, and poloxamer 407 were studied in mice for their capacity to perturb serum lipids, cystatin C, and chitotriosidase-1. Gadolinium and carboxymethylated ß-glucan dosed separately to control mice had no effect on serum lipids, whereas carboxymethylated ß-glucan, but not gadolinium, exerted a significant (p<0.01) and unexpected hypolipidemic effect in poloxamer 407-induced hyperlipidemic mice. An acute hyperlipidemic state (â¼4 days), induced with poloxamer 407 administration alone, resulted in a significant (p<0.01) time-dependent decrease and increase in serum cystatin C and chitotriosidase, respectively. Carboxymethylated ß-glucan administration to hyperlipidemic mice significantly (p<0.05) increased the serum concentration of cystatin C, but significantly (p<0.01) decreased chitotriosidase activity, when each was compared to mice treated with poloxamer 407 only. Gadolinium administration caused a significant decrease in serum chitotriosidase activity in both controls (p<0.01) and poloxamer 407-induced hyperlipidemic (p<0.001) mice, but had no effect on the concentration of cystatin C in either controls or poloxamer 407-induced hyperlipidemic mice. Gadolinium administration resulted in both morphological and functional changes to liver macrophages, which included incorporation of excess lipids, especially when simultaneously administered with poloxamer 407. It is suggested that serum cystatin C and chitotriosidase may represent potential early biomarkers for eventual atherosclerosis in the poloxamer 407-induced mouse model of atherogenesis, and that two compounds known to either increase (carboxymethylated ß-glucan) or decrease (gadolinium chloride) the number of macrophages in vivo were able to modulate serum chitotriosidase activity, This, in turn, would appear to support the premise that serum chitotriosidase activity may be a more sensitive indicator of macrophage involvement than cystatin C in the context of future atherosclerosis.
Assuntos
Aterosclerose/diagnóstico , Cistatina C/sangue , Dislipidemias/induzido quimicamente , Hexosaminidases/sangue , Poloxâmero/toxicidade , Animais , Aterosclerose/sangue , Aterosclerose/enzimologia , Biomarcadores/sangue , Modelos Animais de Doenças , Dislipidemias/sangue , Dislipidemias/enzimologia , Diagnóstico Precoce , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos CBARESUMO
Enhanced expression and activity of chitotriosidase in humans is regarded as a marker of atherosclerosis. However, it remains unclear, whether this increase is related to lipemia or enhanced secretion of the enzyme by activated macrophages in the atherosclerotic plaques. It was shown that acute lipemia in mice caused by single administration of poloxamer 407 (P-407) in a dose of 300 mg/kg is accompanied by an increase in serum chitotriosidase activity (24 h) that correlated with elevated content of total cholesterol and triglycerides. Preliminary administration of (1-3)-ß-D-glycan prevented the P-407-induced increase in chitotriosidase activity, probably due to the hypolipidemic action of (1-3)-ß-D-glycan. The relationship between changes in chitotriosidase activity with atherogenic fractions and subfractions of serum lipoproteins during lipemia is discussed.
Assuntos
Hexosaminidases/sangue , Hiperlipidemias/enzimologia , Hipolipemiantes/uso terapêutico , Polissacarídeos/uso terapêutico , Animais , Masculino , Camundongos , Camundongos Endogâmicos CBARESUMO
The biochemical data on the influence of perturbed geomagnetic field on the hormonal-mediator regulation systems are presented. The possibility of biological effects modification under combined action of perturbed geomagnetic field and high temperature of environment is discussed.
Assuntos
Campos Eletromagnéticos , Febre/metabolismo , 11-Hidroxicorticosteroides/metabolismo , Animais , Epinefrina/metabolismo , Feminino , Norepinefrina/metabolismo , Especificidade de Órgãos , RatosRESUMO
The authors observed 53 patients with odontogenous inflammatory processes of the maxillary sinus. In 27 patients there was a neurocirculatory dystonia. The surgical treatment gave an improvement in the course of neurocirculatory dystonias and in a number of cases a complete recovery of the patients was achieved.