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1.
Int J Comput Assist Radiol Surg ; 16(4): 579-588, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33770362

RESUMO

PURPOSE: The main purpose of this work was to develop an efficient approach for segmentation of structures that are relevant for diagnosis and treatment of obstructive sleep apnea syndrome (OSAS), namely pharynx, tongue, and soft palate, from mid-sagittal magnetic resonance imaging (MR) data. This framework will be applied to big data acquired within an on-going epidemiological study from a general population. METHODS: A deep cascaded framework for subsequent segmentation of pharynx, tongue, and soft palate is presented. The pharyngeal structure was segmented first, since the airway was clearly visible in the T1-weighted sequence. Thereafter, it was used as an anatomical landmark for tongue location. Finally, the soft palate region was extracted using segmented tongue and pharynx structures and used as input for a deep network. In each segmentation step, a UNet-like architecture was applied. RESULTS: The result assessment was performed qualitatively by comparing the region boundaries obtained from the expert to the framework results and quantitatively using the standard Dice coefficient metric. Additionally, cross-validation was applied to ensure that the framework performance did not depend on the specific selection of the validation set. The average Dice coefficients on the test set were [Formula: see text], [Formula: see text], and [Formula: see text] for tongue, pharynx, and soft palate tissues, respectively. The results were similar to other approaches and consistent with expert readings. CONCLUSION: Due to high speed and efficiency, the framework will be applied for big epidemiological data with thousands of participants acquired within the Study of Health in Pomerania as well as other epidemiological studies to provide information on the anatomical structures and aspects that constitute important risk factors to the OSAS development.

2.
Sleep ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33017007

RESUMO

Advanced brain ageing is commonly regarded as a risk factor for neurodegenerative diseases, e.g. Alzheimer's dementia, and it was suggested that sleep disorders such as obstructive sleep apnoea (OSA) are significantly contributing factors to these neurodegenerative processes. To determine the association between OSA and advanced brain ageing, we investigated the specific effect of two indices quantifying OSA, namely the apnoea-hypopnea index (AHI) and the oxygen desaturation index (ODI), on brain age, a score quantifying age-related brain patterns in 169 brain regions, using magnetic resonance imaging and overnight polysomnography data from 690 participants (48.8% women, mean age 52.5±13.4 years) of the Study of Health in Pomerania. We additionally investigated the mediating effect of subclinical inflammation parameters on these associations via a causal mediation analysis. AHI and ODI were both positively associated with brain age (AHI std. effect [95% CI]: 0.07 [0.03; 0.12], p-value: 0.002; ODI std. effect [95% CI]: 0.09 [0.04; 0.13], p-value: <0.0003). The effects remained stable in the presence of various confounders such as diabetes and were partially mediated by the white blood cell count, indicating a subclinical inflammation process. Our results reveal an association between OSA and brain age, indicating subtle but widespread age-related changes in regional brain structures, in one of the largest general population studies to date, warranting further examination of OSA in the prevention of neurodegenerative diseases.

3.
J Control Release ; 327: 1-7, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-32781172

RESUMO

For the therapy of esophageal diseases such as eosinophilic esophagitis, there are no possibilities of local targeted therapy. This publication describes a novel, innovative drug delivery concept, that enables a targeted, long-lasting administration of drug substances to the esophageal mucosa. In addition to a comprehensive in-vitro characterization of the dosage form, this work includes a proof-of-concept study with healthy volunteers, which shows the functionality and acceptance of this novel drug delivery concept. This novel drug delivery technology enables for the first time a targeted, local and long-lasting therapy of the esophagus.

4.
Mol Psychiatry ; 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32424236

RESUMO

Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted "brain age" and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen's d = 0.14, 95% CI: 0.08-0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates.

5.
Neuropsychobiology ; 79(3): 233-244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32146473

RESUMO

BACKGROUND: Alexithymia is a personality trait characterized by difficulties in identifying and describing emotions and associated with various psychiatric disorders. Neuroimaging studies found evidence for morphological and functional brain alterations in alexithymic subjects. However, the neurobiological mechanisms underlying alexithymia remain incompletely understood. METHODS: We study the association of alexithymia with cortical correlation networks in a large community-dwelling sample of the Study of Health in Pomerania. Our analysis includes data of n = 2,199 individuals (49.4% females, age = 52.1 ± 13.6 years) which were divided into a low and high alexithymic group by a median split of the Toronto Alexithymia Scale. Cortical correlation networks were constructed based on the mean thicknesses of 68 regions, and differences in centralities were investigated. RESULTS: We found a significantly increased centrality of the right paracentral lobule in the high alexithymia network after correction for multiple testing. Several other regions with motoric and sensory functions showed altered centrality on a nominally significant level. CONCLUSIONS: Finding increased centrality of the paracentral lobule, a brain area with sensory as well as motoric features and involvement in bowel and bladder voiding, may contribute to explain the association of alexithymia with functional somatic disorders and chronic pain syndromes.

6.
Transl Psychiatry ; 10(1): 100, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198361

RESUMO

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

7.
Hum Brain Mapp ; 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32198905

RESUMO

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = -0.164 to -0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = -0.173 to -0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.

8.
Cereb Cortex ; 30(2): 575-586, 2020 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-31240317

RESUMO

Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4-97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.

9.
PLoS One ; 14(9): e0222682, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31560692

RESUMO

PURPOSE: To provide population-based reference values for cervical spinal canal parameters and vertebral body (VB) width and to study their associations with sex, age, body height, body weight and body mass index (BMI) using MRI. METHODS: Cross-sectional analyses included data from 2,453 participants, aged 21-89 years, of the population-based Study of Health in Pomerania (SHIP) who underwent whole-body MRI at 1.5 Tesla between July 2008 and March 2011. A standardised reading was performed for the C2-C7 cervical spine levels at sagittal T2 TSE weighted sequences. RESULTS: Reference intervals for spinal canal parameters were similar in males and females, while VB width was on average 2.1-2.2 mm larger in males. Age effects were only substantial regarding VB width with a 0.5 mm per ten-year age increase. Body height effects were only substantial regarding the osseous spinal canal and VB width. Body weight and BMI effects are mostly not substantial. CONCLUSIONS: Our study provides MRI-based reference values for the cervical spinal canal parameters in an adult Caucasian population. Except for VB width, associations with sex, age and somatometric measures are mostly small and thus have only limited clinical implications. Some available cut-off values may need a revision because they likely overestimate risks.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Imagem por Ressonância Magnética/normas , Canal Vertebral/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estatura , Índice de Massa Corporal , Peso Corporal , Vértebras Cervicais/anatomia & histologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Canal Vertebral/anatomia & histologia , Adulto Jovem
10.
Insights Imaging ; 10(1): 99, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31549246

RESUMO

BACKGROUND: This study aimed to prospectively investigate patients' satisfaction with briefings before computed tomography (CT) examinations, determine feasibility, and identify factors influencing patient satisfaction independent of patient and physician characteristics. METHODS: One hundred sixty patients received information by a radiologist prior to contrast-enhanced CT examinations in an open, prospective, two-center, cross-sectional study (including the introduction of the radiologist, procedure, radiation exposure, possible side effects, and alternatives). Afterwards, patients and radiologists evaluated the briefing using a standardized questionnaire. Additionally, factors such as age, socioeconomic status, inpatient/outpatient status, length of the radiologist's professional experience, duration of the briefing, clarity of the radiologist's explanations as perceived by patients, and the duration of communication were obtained in this questionnaire. Subsequently, three classes of influencing factors were defined and entered stepwise into a hierarchical regression. RESULTS: Patient satisfaction ratings differed significantly by type of hospitalization, perceived type of communication, and patient gender. Hierarchical regression analysis revealed that perceived clarity was the strongest predictor of patients' satisfaction when controlling for the patient and physician characteristics. CONCLUSIONS: Patients appeared to be satisfied with the briefing prior to CT examination. The mean briefing time (2 min 35 s) seemed feasible. Patients' demographics influenced satisfaction. To improve patients' satisfaction with briefings before contrast-enhanced CT, radiologists should aim to clarify their communication.

11.
Neuroradiology ; 61(10): 1165-1172, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31372674

RESUMO

PURPOSE: To examine the prevalence of the so-called bovine aortic arch variation (common origin of the brachiocephalic trunk and the left common carotid artery) in embolic stroke patients, compared with a control group. METHODS: Aortic arch branching patterns were retrospectively evaluated in 474 individuals with (n = 152) and without (n = 322) acute embolic stroke of the anterior circulation. Contrast-enhanced CT scans of the chest and neck (arterial contrast phase, 1-2-mm slice thickness) were used to evaluate aortic arch anatomy. The stroke cohort included 152 patients who were treated for embolic strokes of the anterior circulation between 2008 and 2018. A total of 322 randomly selected patients who had received thoracic CT angiographies within the same time frame were included as a control group. RESULTS: With a prevalence of 25.7%, the bovine aortic arch variant was significantly more common among patients suffering from embolic strokes, compared with 17.1% of control patients (p = 0.039, OR = 1.67, 95%CI = 1.05-1.97). Stroke patients were more likely to show the bovine arch subtype B (left common carotid artery originating from the brachiocephalic trunk instead of the aortic arch) (10.5% vs. 5.0%, p = 0.039, OR = 2.25, 95%CI = 1.09-4.63), while subtype A (V-shaped common aortic origin of the brachiocephalic trunk and the left carotid) was similarly common in both groups. There was no significant difference regarding the frequency of other commonly observed variant branching patterns of the aortic arch. CONCLUSION: The bovine aortic arch, particularly the bovine arch subtype B, was significantly more common among embolic stroke patients. This might be due to altered hemodynamic properties within the bovine arch.


Assuntos
Aorta Torácica/anormalidades , Biomarcadores , Tronco Braquiocefálico/anormalidades , Artéria Carótida Primitiva/anormalidades , Embolia Intracraniana/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Tronco Braquiocefálico/diagnóstico por imagem , Artéria Carótida Primitiva/diagnóstico por imagem , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Estudos Transversais , Feminino , Humanos , Aumento da Imagem , Embolia Intracraniana/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
13.
Curr Biol ; 29(1): 120-127.e5, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30554901

RESUMO

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1-4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape.


Assuntos
Evolução Biológica , Hibridização Genética , Homem de Neandertal/anatomia & histologia , Crânio/anatomia & histologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Fósseis , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Fenótipo , Adulto Jovem
14.
Thyroid ; 28(11): 1434-1442, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30259797

RESUMO

BACKGROUND: Previous patient studies suggest that thyroid dysfunction affects volumes of particular regions of the brain. So far, population-based data related to this topic are lacking. The aim of this study was to investigate associations of serum levels of thyrotropin (TSH), free triiodothyronine, and free thyroxine (fT4) with total brain volume, gray matter volume, white matter volume (WMV), and hippocampal volume (HV) in a population-based study. METHODS: Data on 2557 individuals were pooled from two independent population-based surveys of the Study of Health in Pomerania conducted in Northeast Germany. Brain volumes were determined from images derived from 1.5 T magnetic resonance imaging. Low and high TSH were defined using the cutoffs 0.40 and 3.29 mIU/L, respectively. Associations between thyroid hormone levels and segmented brain volumes were analyzed by linear regression models. Further, voxel-based morphometry was conducted to search for associations with thyroid hormone levels in a hypothesis-free way throughout the whole brain. All models were adjusted for confounders. RESULTS: Only 9/70 individuals with high TSH had low free triiodothyronine or fT4 levels. Individuals with high TSH had significantly lower total brain volume (ß = -26.9 [confidence interval (CI) -49.0 to -4.8]; p = 0.017), WMV (ß = -16.1 [CI -29.4 to -2.7]; p = 0.018), and HV (ß = -223 [CI -395 to -50]; p = 0.011) than individuals with TSH within the reference range, while low TSH was not significantly associated with any of the brain volumes. Voxel-based morphometry analyses revealed a significant positive association with serum fT4 levels in the left middle frontal gyrus. CONCLUSIONS: In conclusion, the results of this study indicate that the subclinical hypothyroid state may lead to a reduced brain volume affecting particularly HV in younger subjects and WMV, which might correspond to subtle microstructural changes in white matter fiber tracts or myelination of the axones. Gray matter seems not to be affected by subclinical hypothyroid states.


Assuntos
Hipocampo/diagnóstico por imagem , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/diagnóstico por imagem , Tireotropina/sangue , Adulto , Idoso , Feminino , Alemanha , Substância Cinzenta/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/fisiologia , Testes de Função Tireóidea , Tiroxina/sangue , Tri-Iodotironina/sangue
15.
Neurology ; 91(9): e832-e842, 2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-30068634

RESUMO

OBJECTIVE: To investigate the association of enlarged perivascular spaces (ePVS) with cognition in elderly without dementia. METHODS: We included 5 studies from the Uniform Neuro-Imaging of Virchow-Robin Space Enlargement (UNIVRSE) consortium, namely the Austrian Stroke Prevention Family Study, Study of Health in Pomerania, Rotterdam Study, Epidemiology of Dementia in Singapore study, and Risk Index for Subclinical Brain Lesions in Hong Kong study. ePVS were counted in 4 regions (mesencephalon, hippocampus, basal ganglia, and centrum semiovale) with harmonized rating across studies. Mini-Mental State Examination (MMSE) and general fluid cognitive ability factor (G-factor) were used to assess cognitive function. For each study, a linear regression model was performed to estimate the effect of ePVS on MMSE and G-factor. Estimates were pooled across studies with the use of inverse variance meta-analysis with fixed- or random-effect models when appropriate. RESULTS: The final sample size consisted of 3,575 persons (age range 63.4-73.2 years, 50.6% women). Total ePVS counts were not significantly associated with MMSE score (mean difference per ePVS score increase 0.001, 95% confidence interval [CI] -0.007 to 0.008, p = 0.885) or G-factor (mean difference per ePVS score increase 0.002, 95% CI -0.001 to 0.006, p = 0.148) in age-, sex-, and education-adjusted models. Adjustments for cardiovascular risk factors and MRI markers did not change the results. Repeating the analyses with region-specific ePVS rendered similar results. CONCLUSIONS: In this study, we found that ePVS counts were not associated with cognitive dysfunction in the general population. Future studies with longitudinal designs are warranted to examine whether ePVS contribute to cognitive decline.


Assuntos
Edema Encefálico/complicações , Artérias Cerebrais/patologia , Transtornos Cognitivos/etiologia , Idoso , Edema Encefálico/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico por imagem , Planejamento em Saúde Comunitária , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
17.
Eur Radiol ; 28(9): 3996-4005, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29541910

RESUMO

OBJECTIVES: Reference ranges of left ventricular (LV) parameters from cardiac magnetic resonance (CMR) were established to investigate the impact of ageing and hypertension as important determinants of cardiac structure and function. METHODS: One thousand five hundred twenty-five contrast-enhanced CMRs were conducted in the Study of Health in Pomerania. LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume (LVSV), ejection fraction (LVEF), and myocardial mass (LVMM) were determined using long- and short-axis steady-state free-precession sequences. The reference population was defined as participants without late enhancement, hypertension, and prior cardiovascular diseases. Reference ranges were established by quantile regression (5th and 95th percentile) and compared with an additional sample of treated and untreated hypertensives. RESULTS: LV volumes in the reference population (n = 634, 300 males, 334 females, 52.1 ± 13.3 years) aged between 20-69 years were lower with higher age (p = 0.001), whereas LVEFs were higher (p ≤ 0.020). LVMM was lower only in males (p = 0.002). Compared with the reference population, hypertension was associated with lower LVEDV in males (n = 258, p ≤ 0.032). Antihypertensive therapy was associated with higher LVEF in males (n = 258, +2.5%, p = 0.002) and females (n = 180, +2.1%, p = 0.001). CONCLUSIONS: Population-based LV reference ranges were derived from contrast-enhanced CMR. Hypertension-related changes were identified by comparing these values with those of hypertensives, and they might be used to monitor cardiac function in these patients. KEY POINTS: • Left ventricular function changed slightly but significantly between 20-69 years. • Reference values of BSA-indexed myocardial mass decreased with age in males. • Hypertension was associated with lower LV end-diastolic volume only in males. • CMR may allow assessing remodelling related to hypertension or antihypertensive treatment.


Assuntos
Envelhecimento/fisiologia , Técnicas de Imagem Cardíaca , Ventrículos do Coração/anatomia & histologia , Hipertensão/fisiopatologia , Imagem por Ressonância Magnética , Disfunção Ventricular Esquerda , Função Ventricular Esquerda , Adulto , Idoso , Superfície Corporal , Meios de Contraste , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Volume Sistólico , Adulto Jovem
18.
MAbs ; 10(1): 55-61, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29120699

RESUMO

Immunotherapy with short term infusion (STI) of monoclonal anti-GD2 antibody (mAb) ch14.18 (4 × 25 mg/m2/d; 8-20 h) in combination with cytokines and 13-cis retinoic acid (RA) prolonged survival in high-risk neuroblastoma (NB) patients. Here, we investigated long-term infusion (LTI) of ch14.18 produced in Chinese hamster ovary cells (ch14.18/CHO; 10 × 10 mg/m2; 24 h) in combination with subcutaneous (s.c.) interleukin-2 (IL-2) in a single center program and report clinical response, toxicity and survival. Fifty-three high-risk NB patients received up to 6 cycles of 100 mg/m2 ch14.18/CHO (d8-17) as LTI combined with 6 × 106 IU/m2 s.c. IL-2 (d1-5; 8-12) and 160 mg/m2 oral RA (d19-32). Pain toxicity was documented with validated pain scores and intravenous (i.v.) morphine usage. Response was assessed in 37/53 evaluable patients following International Neuroblastoma Risk Group criteria. Progression-free (PFS) and overall survival (OS) was analyzed by the Kaplan-Meier method and compared to a matched historical control group from the database of AIEOP, the "Italian Pediatric Ematology and Oncology Association". LTI of ch14.18/CHO showed acceptable toxicity profile indicated by low pain scores, reduced i.v. morphine usage and low frequency of Grade ≥3 adverse events that allowed outpatient treatment. We observed a best response rate of 40.5% (15/37; 5 CR, 10 PR), 4-year (4 y) PFS of 33.1% (observation 0.1- 4.9 y, mean: 2.2 y) and a 4 y OS of 47.7% (observation 0.27 - 5.20 y, mean: 3.6 y). Survival of the entire cohort (53/53) and the relapsed patients (29/53) was significantly improved compared to historical controls. LTI of ch14.18/CHO thus shows an acceptable toxicity profile, objective clinical responses and a strong signal of clinical efficacy in NB patients.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gangliosídeos/imunologia , Imunoterapia/métodos , Neuroblastoma/terapia , Adolescente , Adulto , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Imunoterapia/efeitos adversos , Lactente , Infusões Intravenosas , Interleucina-2/administração & dosagem , Isotretinoína/administração & dosagem , Masculino , Neuroblastoma/imunologia , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Intervalo Livre de Progressão , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Drug Saf Case Rep ; 4(1): 7, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28343290

RESUMO

Intramuscular injection of diclofenac is still frequently practiced, although there is ample evidence that the risk of local tissue intolerability is highly underestimated. The aim of this study was to evaluate local toxicity in a patient using magnetic resonance imaging. A patient who gave written informed consent received a medically indicated intramuscular administration of diclofenac 75 mg/2 mL. Simultaneously with magnetic resonance imaging of the depot, a clinical-chemical evaluation and quantification of diclofenac in plasma was performed. A manifold enhancement of the T2-weighted magnetic resonance signal was observed in a muscle area of approximately 60 mL volume, with maximum signal intensity 30 min after injection, the time of maximum diclofenac plasma exposure. Plasma creatine kinase activity was elevated approximately sixfold within 8 h and normalized within 1 week, whereas the magnetic resonance enhancement disappeared within 5 weeks. Interestingly, the patient did not complain about any clinical symptoms at the injection site. Asymptomatic tissue injury after intramuscular injection of diclofenac, caused by intramuscular dosing, can be reliably evaluated by magnetic resonance imaging and should be applied early during the development of parenteral dosage forms. Clinical Trials Registration Number: BB130/16 (Ethics Committee of the University Medicine Greifswald).

20.
Am J Med Genet B Neuropsychiatr Genet ; 174(3): 324-332, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28304149

RESUMO

Schizophrenia is associated with brain structural abnormalities including gray and white matter volume reductions. Whether these alterations are caused by genetic risk variants for schizophrenia is unclear. Previous attempts to detect associations between polygenic factors for schizophrenia and structural brain phenotypes in healthy subjects have been negative or remain non-replicated. In this study, we used genetic risk scores that were based on the accumulated effect of selected risk variants for schizophrenia belonging to specific biological systems like synaptic function, neurodevelopment, calcium signaling, and glutamatergic neurotransmission. We hypothesized that this "biologically informed" approach would provide the missing link between genetic risk for schizophrenia and brain structural phenotypes. We applied whole-brain voxel-based morphometry (VBM) analyses in two population-based target samples and subsequent regions of interest (ROIs) analyses in an independent replication sample (total N = 2725). No consistent association between the genetic scores and brain volumes were observed in the investigated samples. These results suggest that in healthy subjects with a higher genetic risk for schizophrenia additional factors apart from common genetic variants (e.g., infection, trauma, rare genetic variants, or gene-gene interactions) are required to induce structural abnormalities of the brain. Further studies are recommended to test for possible gene-gene or gene-environment effects. © 2017 Wiley Periodicals, Inc.


Assuntos
Encéfalo/fisiopatologia , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Adulto , Encéfalo/anatomia & histologia , Mapeamento Encefálico/métodos , Feminino , Previsões , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão/genética , Fatores de Risco
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