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Background and Objectives: This study was performed for the purpose of assessing whether antiepileptic levetiracetam treatment produces a change in brain volumes in children with epilepsy. To that end, we compared the volumes of the basal ganglia (caudate nucleus, putamen, globus, hip-pocampus, and thalamus) at magnetic resonance imaging (MRI) before and after treatment (months 18-24) in pediatric epilepsy patients using levetiracetam. Materials and Methods: This retrospective study involved a volumetric comparison of patients presenting to the Balikesir University Medical Faculty pediatric neurology clinic between 01.08.2019 and 01.11.2023 and diagnosed with epilepsy, and who underwent cranial MRI before and 18-24 months after treatment at the radiology department. The demographic and clinical characteristics (age, sex, family history of epilepsy, type of epilepsy, and EEG features (normal, abnormal, epileptiform)) of the patients included in the study were recorded. Results: The comparison of basal ganglia volumes at cranial MRI before and at months 18-24 of treatment revealed significant differences in the left caudate nucleus, right putamen, left putamen, left globus pallidus, right thalamus, left thalamus, and right hippocampal regions. Conclusions: In conclusion, differing findings are encountered at cranial imaging in patients with epilepsy, depending on the seizure frequency, activity, and the type of antiepileptic drugs used. This study compared basal ganglia volumes on cranial MRIs taken before and 18-24 months after treatment in pediatric epilepsy patients using levetiracetam. A significant increase was observed in the volumes of basal ganglia (caudate nucleus, putamen, globus pallidus, hippocampus, and thalamus) on the MRIs of pediatric epilepsy patients using levetiracetam.
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Anticonvulsivantes , Epilepsia , Levetiracetam , Imagen por Resonancia Magnética , Humanos , Levetiracetam/uso terapéutico , Femenino , Masculino , Niño , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Anticonvulsivantes/uso terapéutico , Adolescente , Epilepsia/tratamiento farmacológico , Preescolar , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/efectos de los fármacos , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacosRESUMEN
BACKGROUND: Very few studies have examined the relationship between calcitonin gene-related peptide (CGRP) and amylin levels and the disease in patients with migraine. The purpose of this study was to compare blood CGRP and amylin levels between pediatric migraine patients and healthy controls and the relationship between CGRP and amylin levels and migraine attack frequency and duration. METHODS: The study involved two separate groups-control and migraine. Thirty-two patients aged 6 to 18 years presenting to the Balikesir University Medical Faculty pediatric neurology clinic and diagnosed with migraine were included. The control group consisted of 32 patients without migraine presenting to the clinic during the same time frame. The patients' demographic data, personal and family histories, migraine type and frequency, headache severity, basic anthropometric measurements (height, weight, and body mass index), and physical and neurological examination findings were recorded. Migraine patients were classified as ictal if the collection of blood specimens coincided with the attack period and as interictal if this was performed between attacks. RESULTS: No statistically significant differences in mean CGRP or amylin levels were determined between the groups (migraine ictal/interictal) or between the migraine patients (in terms of gender or attack frequency and duration). CONCLUSION: Elucidating the complex processes involved in the pathogenesis of migraine is important in terms of our ability to develop new treatments and therapeutic strategies. This study aimed to evaluate CGRP and amylin levels in patients with pediatric migraine (in the ictal and interictal periods) compared with those in healthy controls.
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We analyzed surface sediments from 12 stations located in Izmir Bay to determine the impact of anthropogenic pollution on dinoflagellate cysts. Forty-three dinoflagellate cyst taxa and two cyst assemblage zones were identified. Zone 1 is characterized by the dominance of cysts of Gymnodinium nolleri, Selenopemphix nephroides, and Operculodinium centrocarpum from the oligotrophic part of Izmir Bay. Zone 2 is in the highly productive inner part of the bay and is characterized by the high abundances of Lingulodinium machaerophorum, Spiniferites ramosus, cysts of Scrippsiella spp., cysts of Polykrikos spp. and Quinquecuspis concreta. We used multivariate statistical analysis (DCA and CCA) on dinoflagellate cysts and environmental variables to support the identification of Zones 1 and 2. Our analyses also revealed that summer and winter chlorophyll-a as well as elevated nitrate and nitrite concentrations are significant parameters in controlling dinoflagellate cyst distribution in Izmir Bay.
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Bahías , Dinoflagelados , Monitoreo del Ambiente , Clorofila A/análisis , Estaciones del Año , Sedimentos Geológicos/químicaRESUMEN
Background and Objectives: The purpose of this study was to apply histopathological and immunohistochemical methods to compare the protective efficacy of melatonin and N-acetylcysteine (NAC) application in rats with experimental brain ischemia/reperfusion (I/R) injury induced through occlusion of the middle cerebral artery (MCA), and to evaluate the protective effect of their combined use. Materials and Methods: Forty-one young adult male Wistar albino rats were divided into five groups-control (n = 8), I/R group (n = 8), melatonin (n = 8), NAC (n = 8), and melatonin + NAC (n = 9). Results: All scores differed between the groups, apart from vascular congestion (p < 0.05). At two-way comparisons, all histological scores were significantly higher in the I/R group than in the control group (p < 0.05). No change occurred in the vascular congestion scores with the administration of melatonin, although decreases were determined in all other scores. These decreases were statistically significant for cellular eosinophilic pyknotic degeneration, vacuolization, and edema (p < 0.05). All histopathological scores in the group administered NAC together with melatonin were significantly lower than in the I/R group (p < 0.05). Conclusions: The combined use of NAC and melatonin, the neuroprotective efficacy of which on histopathological parameters is shown in this study, now needs to be supported by further research.
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Melatonina , Daño por Reperfusión , Ratas , Masculino , Animales , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Melatonina/farmacología , Melatonina/uso terapéutico , Ratas Wistar , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
AIM: This research was intended to evaluate the clinical and laboratory findings of children presenting to our pediatric neurology clinic with symptoms potentially linked to vitamin D deficiency and with low vitamin D levels and the distribution of those findings by sex, age groups, and vitamin D levels. METHODS: This retrospective study involved patients presenting to our clinic with symptoms potentially associated with vitamin D deficiency and low serum concentrations of 25 OH vitamin D (25 OH D) (<75 nmol/L, 30 µg/mL). Patients' movement disorders and central nervous system-related symptoms at the time of presentation and serum 25 OH D, calcium (Ca), phosphorus (P), and magnesium (Mg) levels were recorded and evaluated in terms of age, sex, and vitamin D levels. RESULTS: Eight hundred twenty-two cases of vitamin D deficiency were included in the study, 50.2% (n = 413) boys and 49.8% (n = 409) girls. Although cases of vitamin D deficiency were present across all the age groups between 1 and 18, they were most common in the 5-14 age range (n = 372, 45.3%). Movement disorders were observed in 14.6% (n = 120) of our cases, and neurological findings associated with the central nervous system were observed in 52.6% (n = 432). The most common accompanying movement in our cases was difficulty remaining in balance (n = 42, 35%), while the most frequent accompanying central nervous system finding was vertigo (n = 99, 22.92%). Other movement disorders encountered included limb shaking (n = 32, 26.7%), abnormal posture (n = 20, 16.67%), easy falling (n = 16, 13.33%), body rigidity (n = 15, 12.5%), and hand clenching (n = 5, 4.17%). Other frequently encountered neurological findings were headache (n = 88, 20.37%), epileptic seizures (n = 83, 19.21%), fainting (n = 58, 13.43%), developmental delay (n = 41, 9.49%), febrile seizures (n = 33, 7.64%), and numbness in the fingers (n = 20, 4.63%). Other neurological findings were sleep disorders (n = 10, 2.31%), nightmares (n = 8, 1.85%), pain in the extremities (n = 7, 1.62%), and sweating and frailty (n = 4, 0.93% for both). Ca, P, and Mg levels were lower in cases with vitamin D levels < 12 µg/mL. The prevalences of both movement disorders and central nervous system findings varied according to age groups, sex, and vitamin D levels. CONCLUSIONS: Our study results show that vitamin D deficiency can present with different neurological findings and that these may vary according to age group, sex, and vitamin D levels. Clinicians must take particular care in pediatric cases with neurological findings in terms of the early diagnosis and treatment of vitamin D deficiency.
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Introduction: Global developmental delay (DD), intellectual disability (ID), and autism spectrum disorder (ASD) are mainly evaluated under the neurodevelopmental disorder framework. In this study, we aimed to determine the genetic diagnosis yield using step-by-step genetic analysis in 38 patients with unexplained ID/DD and/or ASD. Methods: In 38 cases (27 male, 11 female) with unexplained ID/DD and/or ASD, chromosomal microarray (CMA) analysis, clinical exome sequencing (CES), and whole-exome sequencing (WES) analysis were applied, respectively. Results: We found a diagnostic rate of only CMA analysis as 21% (8/38) presenting 8 pathogenic and likely pathogenic CNVs. The rate of patients diagnosed with CES/WES methods was 32.2% (10/31). When all pathogenic and likely pathogenic variants were evaluated, the diagnosis rate was 44.7% (17/38). A dual diagnosis was obtained in a case with 16p11.2 microduplication and de novo SNV. We identified eight novel variants: TUBA1A (c.787C>G), TMEM63A (c.334-2A>G), YY1AP1 (c.2051_2052del), ABCA13 (c.12064C>T), ABCA13 (c.13187G>A), USP9X (c.1189T>C), ANKRD17 (c.328_330dup), and GRIA4 (c.17G>A). Conclusion: We present diagnostic rates of a complementary approach to genetic analysis (CMA, CES, and WES). The combined use of genetic analysis methods in unexplained ID/DD and/or ASD cases has contributed significantly to diagnosis rates. Also, we present detailed clinical characteristics to improve genotype-phenotype correlation in the literature for rare and novel variants.
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Lumbar puncture (LP) is widely employed to evaluate infectious, neurological and metabolic diseases in the newborn. Neonatal LP is a difficult procedure with 45-54% success rates. Although there are studies examining traumatic LP failure, studies on the effects of needle sizes are limited. This study was intended to investigate the effect of needle sizes on LP traumatization. Term and premature babies who underwent LP in the neonatal intensive care unit between 30 November 2017 and 30 July 2019 were included in the study by retrospective file scanning. LP was performed by a pediatric or neonatal specialist using a 22 Gauge pen (G) or 25 G pen spinal needle in all cases, with all patients being placed in the lateral decubitus position. The primary outcome was to evaluate the effect of needle sizes used in LP on traumatization. The secondary outcome was to evaluate traumatization rates and complications. A statistically significant difference was determined in the rate of traumatized LP and desaturation development between needle sizes and CSF microscopic findings (p = 0.031, p = 0.005, and p = 0.006, respectively). The study data show that 25 G pen-tip spinal needles cause less traumatic LP in neonates than 22 G pen-tip spinal needles.
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AIM: The purpose of this study was to compare the electrocardiographic parameters before and at the sixth month of treatment of patients diagnosed with epilepsy and who were started on levetiracetam therapy. METHODS: The files of 30 patients diagnosed with epilepsy and on levetiracetam therapy were examined in this study. Clinical findings, electroencephalography (EEG), cranial magnetic resonance imaging (MRI) and electrocardiography (ECG) data before and at the sixth month of treatment were recorded. RESULTS: The patients' mean age was 10.93 ± 3.74 (4-17) years; 16 (53.33%) patients were boys. In total, 13 (43.3%) were found to experience focal seizures, and 17 (56.7%) generalized epilepsy-type seizures. Comparison of the ECG parameters (PR interval, QTc, QT interval, and QRS duration) revealed a shortening in the PR interval and QTc values at the sixth month of treatment, although the changes were not statistically significant. No significant differences in terms of gender and epilepsy types were observed between the ECG parameters before treatment and at the sixth month (p > 0.05). CONCLUSION: In this study, levetiracetam was found to have no effect on ECG parameters.
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Electrocardiografía , Epilepsia , Masculino , Humanos , Niño , Adolescente , Femenino , Levetiracetam/uso terapéutico , Electrocardiografía/métodos , Epilepsia/tratamiento farmacológico , Epilepsia/diagnóstico , ConvulsionesRESUMEN
AIM: The purpose of this study was to evaluate the relationship between the lunar cycle and attacks observed in patients diagnosed with migraine and under follow-up in our pediatric neurology clinic. METHODS: Cases diagnosed with migraine and under follow-up at the Balikesir University Medical Faculty Pediatric Neurology Clinic, Turkey, undergoing attacks between 01.09.2019 and 01.09.2021, and whose attacks were recorded were included in the study. Patients' migraine attacks were investigated retrospectively, and the stage of the lunar cycle at which they occurred, based on the lunar calendar, was determined. RESULTS: The mean age of the patients in the study was 13.39 ± 2.64 (8-17) years. Female gender was observed in the majority of attacks in all lunar cycles, and was most common in the first quarter. Headache was most common in the frontal region during the first quarter and full moon, and auras were also most frequent in the first quarter. Stress and exercise were the most frequent migraine-triggering factors in the first and third quarters, and in the full moon. Migraine attacks were shortest in duration in the full moon, and longest in the first quarter. The frequency of attacks (per week) was highest in the new moon and third quarter, and lowest in the full moon. CONCLUSIONS: This study investigated the relationship between migraine attack characteristics in children and the lunar cycle. It represents the first such investigation of the association between the lunar cycle and pediatric migraine attacks.
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Trastornos Migrañosos , Luna , Humanos , Femenino , Niño , Adolescente , Estudios Retrospectivos , Trastornos Migrañosos/epidemiología , Turquía/epidemiologíaRESUMEN
Kleefstra syndrome (KS), previously referred to as 9q subtelomeric deletion syndrome (9qSTDS), is characterised by moderate to severe developmental delay/mental retardation, childhood hypotonia, and brachy-microcephaly (main clinical phenotype), midface hypoplasia, prognathism, lip and eyebrow shape anomalies. The true prevalence of KS is unknown, but it is estimated that it occurs with a frequency of 1/200.000 in cases with mental retardation. On literature search, approximately 110 patients have been reported so far. Genetic analysis should be planned and interdisciplinary monitoring should be provided in cases suspected to have KS. Key Words: Child, Genetic disorder, Kleefstra Syndrome, Dysmorphism.
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Anomalías Craneofaciales , Discapacidad Intelectual , Niño , Deleción Cromosómica , Cromosomas Humanos Par 9 , Anomalías Craneofaciales/diagnóstico , Anomalías Craneofaciales/epidemiología , Anomalías Craneofaciales/genética , Cardiopatías Congénitas , Humanos , Discapacidad Intelectual/epidemiología , Discapacidad Intelectual/genética , SíndromeRESUMEN
BACKGROUND: Side effects of antiepileptic drugs vary depending on the drug itself, drug dose and duration of use. One of these side effects is related to vision. METHODS: Patients who had been ordered visual evoked potential (VEP) measurements for various reasons between the dates of 01.10.2017 and 01.10.2019 at a pediatric neurology outpatient clinic and who were on levetiracetam monotherapy for at least six months for the treatment of focal/generalized epilepsy were included in the study and their files were scanned retrospectively (Study Group: SG). Patient files were evaluated for age, gender, dose and duration of levetiracetam use, presence of a family history of epilepsy, EEG result, cranial magnetic resonance imaging and VEP test results and the parameters were recorded. Twenty-four patients of similar age range without epilepsy were included in the study as the control group (CG). RESULTS: Eighteen patients 8 boys (44.4%), 10 girls (54.6%) and 24 healthy controls 9 boys (37.5%), 15 girls (62.5%) were included in the study and control groups, respectively. No statistically significant difference was found when the mean VEP latencies were compared between the patient and control groups for the right (p: 0.451) and left (p: 0.323) eyes. There was a statistically significant difference between the groups, respectively, when VEP amplitudes of the right and left eyes of the SG and CG were compared (p: 0.001; p: 0.001). There is no correlation between levetiracetam dose and duration of treatment and VEP parameters. CONCLUSIONS: The data obtained in this study showed that levetiracetam use affected VEP amplitude outcome but did not affect VEP latency outcome in pediatric patients.
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The aim of this study was to evaluate vitamin B12 levels in the patients diagnosed with neurofibromatosis type 1 (NF1) and to compare them with a healthy group. In this study, the files of the patients, who were admitted to the pediatric neurology outpatient clinic of a tertiary university hospital and were followed up after being diagnosed with neurofibromatosis type 1 during the 15-month period, were evaluated retrospectively (Study group). Demographic data, and laboratory test results (complete blood count, iron, iron-binding capacity, ferritin, vitamin B12 and folate) were recorded from the patient files. The cases admitted to the hospital for routine child health examination in the same period were taken as the control group. Vitamin B12 levels were statistically significantly lower in the study group compared to the control group (p=0.012). This study is the first study evaluating vitamin B12 levels in NF1 patients. Key Words: Neurofibromatosis type 1, Neurofibromin, Nutrition, Vitamin B12.
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Neurofibromatosis 1 , Deficiencia de Vitamina B 12 , Niño , Ácido Fólico , Humanos , Estudios Retrospectivos , Vitamina B 12 , Deficiencia de Vitamina B 12/diagnósticoRESUMEN
Migraine is a recurrent, primary cause of headache. Although prophylactic vitamin B12 therapy is used on migraine patients, there is a limited number of studies examining the levels of B12 vitamin and folic acid in pediatric patients diagnosed with migraine. The study group (Group 1) included 65 pediatric patients diagnosed with migraine in the Pediatric neurology outpatient clinic, and 87 healthy cases admitted to the general pediatric clinic were included in the control group (Group 2). Complete blood count parameters, vitamin B12, folic acid, ferritin, and 25 OH D vitamin levels of the study and control groups were compared. The mean vitamin B12 level was 196.42 ± 95.54 pg/mL (59-499) in Group 1 and 240 ± 105.24 pg/mL (74-619) in Group 2. The mean folic acid level was 8.85 ± 3.49 pg/mL (3.68-23.70) in Group 1 and 7.24 ± 7.17 pg/mL (1.11-35.50) in Group 2. There was a statistically significant difference between Group 1 and 2 in terms of vitamin B12 and folic acid levels (p = 0.008, p = 0.00). The results of this study indicate the requirement for routine evaluation of vitamin B12 and folic acid levels in pediatric patients diagnosed with migraine.
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Ácido Fólico/sangre , Trastornos Migrañosos/sangre , Trastornos Migrañosos/diagnóstico , Vitamina B 12/sangre , Adolescente , Biomarcadores/sangre , Niño , Femenino , Humanos , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: The color of all-ceramic restorations is one of the main criteria to achieve esthetical success. Many factors such as ceramic thickness, condensation techniques, firing temperature, and numbers can affect the final color of restoration. The purpose of this study was to investigate the color changes in alumina-based ceramic system according to ceramic shade and thickness during the multiple firings. MATERIALS AND METHODS: Sixty disc-shaped specimens with two different veneering porcelain shades (A1 or A3), and with three different ceramic thicknesses (0.5, 1, or 1.5 mm), were fabricated from an alumina-based ceramic system. Multiple firings (3, 5, 7, or 9 firings) were performed, and color changes (ΔE00 ) were determined using a spectrophotometer. Repeated-measures ANOVA were used to analyze the data. The Duncan test was used for multiple comparisons (α = .05). RESULTS: The L*a*b* values of the specimens were affected by the number of firings (3, 5, 7, or 9), veneering ceramic shades (A1 or A3) and veneering ceramic thicknesses (0.5, 1, or 1.5 mm). Significant interactions were present between the number of firings, veneering ceramic shade, and veneering ceramic thickness for L* (p < .001), a* (p < .001), and b* (p < .001) values. CONCLUSIONS: No statistically significant color change was observed between 3rd and 9th firings. CLINICAL SIGNIFICANCE: Veneering ceramic shade, veneering ceramic thickness, and number of firings should be carefully considered to obtain an acceptable color match of the definitive restorations.
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Óxido de Aluminio , Coloración de Prótesis , Cerámica , Color , Porcelana Dental , Coronas con Frente Estético , Ensayo de Materiales , Propiedades de SuperficieRESUMEN
We report a patient with anal atresia, anophthalmia and intestinal neuronal dysplasia type A.
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The spatial distribution of dinoflagellate cysts was studied to understand the impact of industrial pollution on the surface sediment of Izmir Bay, Turkey. Forty two dinoflagellate cyst morphotypes belonging to 12 genera were identified and qualified at 12 sampling points. The cyst of Gymnodinium nolleri dominated the bay and had the highest abundance in most of the stations, following Spiniferites bulloideus and Lingulodinium machaerophorum. The highest cyst concentration was recorded in the inner part of the bay. Cyst concentration ranged between 384 and 9944 cyst g(-1) dry weight of sediment in the sampling area. Sediment metal concentrations were determined. Heavy metal levels in Izmir Inner Bay were higher than the Middle and Outer Bay. L. machaerophorum, Dubridinium caperatum and Polykrikos kofoidii showed significant positive correlation with some metals (Cd, Pb, Cu, Zn) and organic carbon content. However, there was no significant correlation between dinoflagellate cyst abundance and sediment type.
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Bahías/química , Dinoflagelados/crecimiento & desarrollo , Monitoreo del Ambiente , Sedimentos Geológicos , Industrias , Metales Pesados/análisis , Turquía , Contaminantes Químicos del Agua/análisisRESUMEN
BACKGROUND: A fine needle aspiration biopsy (FNAB) of thyroid nodules - the least invasive and most accurate method used to investigate malignant lesions - may yield non-diagnostic specimens even under ultrasonographic guidance. PURPOSE: To evaluate the effects of thyroid nodule volume and extent of cystic degeneration on both the non-diagnostic specimen ratio as well as cytopathologist's definitive cytological diagnosis time. MATERIAL AND METHODS: In this single center study, FNAB was performed on 505 patients with single thyroid nodules greater than 10 mm. Nodule volume was calculated prior to FNAB and cystic degeneration ratio was recorded. All biopsies were performed by a single radiologist who also prepared specimen slides. Specimen adequacy and final diagnosis were made in the pathology laboratory by a single-blinded cytopathologist based on the Bethesda system. Definitive cytological diagnosis time was recorded upon reaching a definitive diagnosis. RESULTS: The specimen adequacy ratio was 85.3%. The mean nodule volume of adequate specimens was larger than those of non-diagnostic samples (6.00 mL vs. 3.05 mL; P = 0.001). There was no correlation between nodule volume and cytopathologist's definitive cytological diagnosis time (r = 0.042). Biopsy of predominantly solid nodules yielded better specimen adequacy ratios compared to predominantly cystic nodules (87.8% vs. 75.3%; P = 0.028). Definitive cytological diagnosis times were longer in predominantly cystic nodules compared to predominantly solid nodules (376 s vs. 294 s; P = 0.019). CONCLUSION: Predominantly cystic nodules are likely to benefit from repeated nodular sampling until the specimen is declared adequate by an on-site cytopathologist. If a cytopathologist is not available, obtaining more specimens per nodule may achieve desired adequacy ratios.
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Biopsia con Aguja Fina , Neoplasias de la Tiroides/patología , Nódulo Tiroideo/patología , Ultrasonografía Intervencional , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Dietary intervention studies have shown that flavanols and inorganic nitrate can improve vascular function, suggesting that these two bioactives may be responsible for beneficial health effects of diets rich in fruits and vegetables. We aimed to study interactions between cocoa flavanols (CF) and nitrate, focusing on absorption, bioavailability, excretion, and efficacy to increase endothelial function. In a double-blind randomized, dose-response crossover study, flow-mediated dilation (FMD) was measured in 15 healthy subjects before and at 1, 2, 3, and 4 h after consumption of CF (1.4-10.9 mg/kg bw) or nitrate (0.1-10 mg/kg bw). To study flavanol-nitrate interactions, an additional intervention trial was performed with nitrate and CF taken in sequence at low and high amounts. FMD was measured before (0 h) and at 1h after ingestion of nitrate (3 or 8.5 mg/kg bw) or water. Then subjects received a CF drink (2.7 or 10.9 mg/kg bw) or a micro- and macronutrient-matched CF-free drink. FMD was measured at 1, 2, and 4 h thereafter. Blood and urine samples were collected and assessed for CF and nitric oxide (NO) metabolites with HPLC and gas-phase reductive chemiluminescence. Finally, intragastric formation of NO after CF and nitrate consumption was investigated. Both CF and nitrate induced similar intake-dependent increases in FMD. Maximal values were achieved at 1 h postingestion and gradually decreased to reach baseline values at 4 h. These effects were additive at low intake levels, whereas CF did not further increase FMD after high nitrate intake. Nitrate did not affect flavanol absorption, bioavailability, or excretion, but CF enhanced nitrate-related gastric NO formation and attenuated the increase in plasma nitrite after nitrate intake. Both flavanols and inorganic nitrate can improve endothelial function in healthy subjects at intake amounts that are achievable with a normal diet. Even low dietary intake of these bioactives may exert relevant effects on endothelial function when ingested together.