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1.
Clin Exp Rheumatol ; 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37976113

RESUMO

OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) commonly presents with diffuse alveolar haemorrhage (DAH) and/or glomerulonephritis. Patients who present with DAH but without kidney involvement have been understudied. METHODS: Patients with DAH diagnosed by bronchoscopy and attributed to AAV over 8.5 years were retrospectively identified through electronic medical records and bronchoscopy reporting software. Patients with end-stage kidney disease (ESKD) or prior kidney transplant were excluded. Characteristics, treatments, and outcomes were abstracted. RESULTS: 30 patients were identified with DAH secondary to AAV. Five with ESKD or prior kidney transplant, and one with concomitant anti-glomerular basement membrane disease, were excluded, leaving 24 patients for analysis. At the time of qualifying bronchoscopy, six patients had no apparent kidney involvement by AAV, while eight of 18 with kidney involvement required dialysis. Of the eight patients dialysed during the initial hospitalisation, four were declared to have ESKD and three died in the subsequent year (one of whom did both). None of the 16 patients without initial dialysis requirement developed kidney involvement requiring dialysis in the subsequent year, though three of the six without initial evidence of kidney involvement by AAV ultimately developed it. No patient without initial kidney involvement died during follow-up. CONCLUSIONS: In our cohort, patients with DAH due to AAV without initial kidney involvement did not develop kidney involvement requiring dialysis or die during the follow-up period, though half of patients without initial evidence of kidney involvement subsequently developed it. Larger studies are warranted to better characterise this population and guide medical management.

2.
J Thromb Thrombolysis ; 49(3): 501-503, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31820264

RESUMO

Nitrous oxide is a commonly abused inhalant by adolescents and young adults. There is limited data describing the adverse effects of nitrous oxide abuse, known colloquially as "whippets". We present a 21-year-old female with no medical history who presented to the emergency department for confusion, hallucinations, weakness, and falls. She was accompanied by her roommates, who endorsed significant nitrous oxide abuse. Imaging revealed a large cerebral sinus venous thrombus with extension into the transverse sinus, sigmoid sinus and internal jugular vein. She had no prior history of venous or arterial thrombosis. Hypercoagulability workup demonstrated an elevated homocysteine level, elevated methylmalonic acid level, and normal cobalamin and folate levels. Additionally, she was found to be 11 weeks pregnant, with no prior spontaneous abortions. Genetic testing was significant for methylenetetrahydrofolate reductase polymorphisms. She was managed with enoxaparin, cobalamin and folate supplementation. Homocysteine and methylmalonic acid levels normalized after cessation of nitrous oxide use, with no recurrence of venous thrombosis. This case represents the first reported patient with a venous thrombus associated with nitrous oxide abuse.


Assuntos
Enoxaparina/administração & dosagem , Ácido Fólico/administração & dosagem , Óxido Nitroso/efeitos adversos , Trombose dos Seios Intracranianos , Trombose Venosa , Vitamina B 12/administração & dosagem , Adulto , Feminino , Humanos , Óxido Nitroso/administração & dosagem , Trombose dos Seios Intracranianos/induzido quimicamente , Trombose dos Seios Intracranianos/diagnóstico por imagem , Trombose dos Seios Intracranianos/tratamento farmacológico , Trombose Venosa/induzido quimicamente , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico
3.
Nanomedicine ; 11(1): 137-45, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25200612

RESUMO

We present the nanosurgery on the cytoskeleton of live cells using AFM based nanorobotics to achieve adhesiolysis and mimic the effect of pathophysiological modulation of intercellular adhesion. Nanosurgery successfully severs the intermediate filament bundles and disrupts cell-cell adhesion similar to the desmosomal protein disassembly in autoimmune disease, or the cationic modulation of desmosome formation. Our nanomechanical analysis revealed that adhesion loss results in a decrease in cellular stiffness in both cases of biochemical modulation of the desmosome junctions and mechanical disruption of intercellular adhesion, supporting the notion that intercellular adhesion through intermediate filaments anchors the cell structure as focal adhesion does and that intermediate filaments are integral components in cell mechanical integrity. The surgical process could potentially help reveal the mechanism of autoimmune pathology-induced cell-cell adhesion loss as well as its related pathways that lead to cell apoptosis.


Assuntos
Filamentos Intermediários/química , Queratinócitos/citologia , Nanomedicina/métodos , Robótica , Cirurgia Assistida por Computador/métodos , Apoptose , Doenças Autoimunes/metabolismo , Cátions , Adesão Celular , Linhagem Celular , Citoesqueleto/metabolismo , Desmossomos/metabolismo , Humanos , Microscopia de Força Atômica , Nanoestruturas , Estresse Mecânico
4.
Artigo em Inglês | MEDLINE | ID: mdl-38961273

RESUMO

BACKGROUND: American Indian (AI) communities are affected by uranium exposure from abandoned mines and naturally contaminated drinking water. Few studies have evaluated geographical differences across AI communities and the role of dietary exposures. OBJECTIVE: We evaluated differences in urinary uranium levels by diet and geographical area among AI participants from the Northern Plains, the Southern Plains, and the Southwest enrolled in the Strong Heart Family Study (SHFS). METHODS: We used food frequency questionnaires to determine dietary sources related to urinary uranium levels for 1,682 SHFS participants in 2001-2003. We calculated adjusted geometric mean ratios (GMRs) of urinary uranium for an interquartile range (IQR) increase in self-reported food group consumption accounting for family clustering and adjusting for sociodemographic variables and other food groups. We determined the percentage of variability in urinary uranium explained by diet. RESULTS: Median (IQR) urinary uranium levels were 0.027 (0.012, 0.057) µg/g creatinine. Urinary uranium levels were higher in Arizona (median 0.039 µg/g) and North Dakota and South Dakota (median 0.038 µg/g) and lower in Oklahoma (median 0.019 µg/g). The adjusted percent increase (95% confidence interval) of urinary uranium levels per IQR increase in reported food intake was 20% (5%, 36%) for organ meat, 11% (1%, 23%) for cereals, and 14% (1%, 29%) for alcoholic drinks. In analyses stratified by study center, the association with organ meat was specific to North Dakota and South Dakota participants. An IQR increase in consumption of fries and chips was inversely associated with urinary uranium levels -11% (-19%, -3%). Overall, we estimated that self-reported dietary exposures explained 1.71% of variability in urine uranium levels. IMPACT: Our paper provides a novel assessment of self-reported food intake and urinary uranium levels in a cohort of American Indian participants. We identify foods (organ meat, cereals, and alcohol) positively associated with urinary uranium levels, find that organ meat consumption is only associated with urine uranium in North Dakota and South Dakota, and estimate that diet explains relatively little variation in total urinary uranium concentrations. Our findings contribute meaningful data toward a more comprehensive estimation of uranium exposure among Native American communities and support the need for high-quality assessments of water and dust uranium exposures in SHFS communities.

5.
J Expo Sci Environ Epidemiol ; 34(1): 77-89, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37558699

RESUMO

BACKGROUND: Chronic exposure to inorganic arsenic (As) and uranium (U) in the United States (US) occurs from unregulated private wells and federally regulated community water systems (CWSs). The contribution of water to total exposure is assumed to be low when water As and U concentrations are low. OBJECTIVE: We examined the contribution of water As and U to urinary biomarkers in the Strong Heart Family Study (SHFS), a prospective study of American Indian communities, and the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective study of racially/ethnically diverse urban U.S. communities. METHODS: We assigned residential zip code-level estimates in CWSs (µg/L) and private wells (90th percentile probability of As >10 µg/L) to up to 1485 and 6722 participants with dietary information and urinary biomarkers in the SHFS (2001-2003) and MESA (2000-2002; 2010-2011), respectively. Urine As was estimated as the sum of inorganic and methylated species, and urine U was total uranium. We used linear mixed-effects models to account for participant clustering and removed the effect of dietary sources via regression adjustment. RESULTS: The median (interquartile range) urine As was 5.32 (3.29, 8.53) and 6.32 (3.34, 12.48) µg/L for SHFS and MESA, respectively, and urine U was 0.037 (0.014, 0.071) and 0.007 (0.003, 0.018) µg/L. In a meta-analysis across both studies, urine As was 11% (95% CI: 3, 20%) higher and urine U was 35% (5, 73%) higher per twofold higher CWS As and U, respectively. In the SHFS, zip-code level factors such as private well and CWS As contributed 46% of variation in urine As, while in MESA, zip-code level factors, e.g., CWS As and U, contribute 30 and 49% of variation in urine As and U, respectively. IMPACT STATEMENT: We found that water from unregulated private wells and regulated CWSs is a major contributor to urinary As and U (an estimated measure of internal dose) in both rural, American Indian populations and urban, racially/ethnically diverse populations nationwide, even at levels below the current regulatory standard. Our findings indicate that additional drinking water interventions, regulations, and policies can have a major impact on reducing total exposures to As and U, which are linked to adverse health effects even at low levels.


Assuntos
Arsênio , Aterosclerose , Urânio , Adulto , Humanos , Água , Estudos Prospectivos , Biomarcadores
6.
Biophys J ; 105(1): 40-7, 2013 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-23823222

RESUMO

Integrins are dynamic transmembrane cation-dependent heterodimers that both anchor cells in position and transduce signals into and out of cells. We used an atomic force microscope (AFM)-based nanorobotic system to measure integrin-binding forces in intact human intestinal epithelial Caco-2 cells. The AFM-based nanorobot enables human-directed, high-accuracy probe positioning and site-specific investigations. Functionalizing the AFM probe with an arginine-glycine-aspartate (RGD)-containing sequence (consensus binding sequence for integrins) allowed us to detect a series of peptide-cell membrane interactions with a median binding force of 115.1 ± 4.9 pN that were not detected in control interactions. Chelating divalent cations from the culture medium abolished these interactions, as did inhibiting intracellular focal adhesion kinase (FAK) using Y15. Adding 1 mM Mg(2+) to the medium caused a rightward shift in the force-binding curve. Adding 1 mM Ca(2+) virtually abolished the RGD-membrane specific interactions and blocked the Mg(2+) effects. Cell adhesion assays demonstrated parallel effects of divalent cations and the FAK inhibitor on cell adhesion. These results demonstrate direct modulation of integrin-binding affinity by both divalent cations and intracellular signal inhibition. Additionally, three binding states (nonspecific, specific inactivated, and specific activated) were delineated from affinity measurements. Although other research has assumed that this process of integrin conformational change causes altered ligand binding, in this work we directly measured these three states in individual integrins in a physiologically based study.


Assuntos
Integrinas/metabolismo , Espaço Intracelular/metabolismo , Microscopia de Força Atômica/métodos , Nanotecnologia/métodos , Robótica , Células CACO-2 , Humanos , Espaço Intracelular/enzimologia , Oligopeptídeos/metabolismo , Ligação Proteica
7.
Nanomedicine ; 9(5): 636-45, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23178285

RESUMO

Distinct biochemical, electrochemical and electromechanical coupling processes of pancreatic ß-cells may well underlie different response patterns of insulin release from glucose and capsaicin stimulation. Intracellular Ca(2+) levels increased rapidly and dose-dependently upon glucose stimulation, accompanied with about threefold rapid increases in cellular stiffness. Subsequently, cellular stiffness diminished rapidly and settled at a value about twofold of the baseline. Capsaicin caused a similar transient increase in intracellular Ca(2+) changes. However, cellular stiffness increased gradually to about twofold until leveling off. The current study characterizes for the first time the biophysical properties underlying glucose-induced biphasic responses of insulin secretion, distinctive from the slow and single-phased stiffness response to capsaicin despite similar changes in intracellular Ca(2+) levels. The integrated AFM nanorobotics and optical investigation enables the fine dissection of mechano-property from ion channel activities in response to specific and non-specific agonist stimulation, providing novel biomechanical markers for the insulin secretion process. FROM THE CLINICAL EDITOR: This study characterizes the biophysical properties underlying glucose-induced biphasic responses of insulin secretion. Integrated AFM nanorobotics and optical investigations provided novel biomechanical markers for the insulin secretion process.


Assuntos
Fenômenos Biofísicos , Insulina/metabolismo , Insulinoma/metabolismo , Nanotecnologia/instrumentação , Robótica/instrumentação , Cálcio/metabolismo , Capsaicina/farmacologia , Linhagem Celular Tumoral , AMP Cíclico/metabolismo , Glucose/farmacologia , Humanos , Secreção de Insulina , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Insulinoma/patologia , Canais Iônicos/efeitos dos fármacos , Canais Iônicos/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Microscopia de Força Atômica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia
8.
JMIR Rehabil Assist Technol ; 10: e43250, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37224276

RESUMO

BACKGROUND: Patients who were incarcerated were disproportionately affected by COVID-19 compared with the general public. Furthermore, the impact of multidisciplinary rehabilitation assessments and interventions on the outcomes of patients admitted to the hospital with COVID-19 is limited. OBJECTIVE: We aimed to compare the functional outcomes of oral intake, mobility, and activity between inmates and noninmates diagnosed with COVID-19 and examine the relationships among these functional measures and discharge destination. METHODS: A retrospective analysis was performed on patients admitted to the hospital for COVID-19 at a large academic medical center. Scores on functional measures including the Functional Oral Intake Scale and Activity Measure for Postacute Care (AM-PAC) were collected and compared between inmates and noninmates. Binary logistic regression models were used to evaluate the odds of whether patients were discharged to the same place they were admitted from and whether patients were being discharged with a total oral diet with no restrictions. Independent variables were considered significant if the 95% CIs of the odds ratios (ORs) did not include 1.0. RESULTS: A total of 83 patients (inmates: n=38; noninmates: n=45) were included in the final analysis. There were no differences between inmates and noninmates in the initial (P=.39) and final Functional Oral Intake Scale scores (P=.35) or in the initial (P=.06 and P=.46), final (P=.43 and P=.79), or change scores (P=.97 and P=.45) on the AM-PAC mobility and activity subscales, respectively. When examining separate regression models using AM-PAC mobility or AM-PAC activity scores as independent variables, greater age upon admission decreased the odds (OR 0.922, 95% CI 0.875-0.972 and OR 0.918, 95% CI 0.871-0.968) of patients being discharged with a total oral diet with no restrictions. The following factors increased the odds of patients being discharged to the same place they were admitted from: being an inmate (OR 5.285, 95% CI 1.334-20.931 and OR 6.083, 95% CI 1.548-23.912), "Other" race (OR 7.596, 95% CI 1.203-47.968 and OR 8.515, 95% CI 1.311-55.291), and female sex (OR 4.671, 95% CI 1.086-20.092 and OR 4.977, 95% CI 1.146-21.615). CONCLUSIONS: The results of this study provide an opportunity to learn how functional measures may be used to better understand discharge outcomes in both inmate and noninmate patients admitted to the hospital with COVID-19 during the initial period of the pandemic.

9.
Planta ; 236(4): 1327-37, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22729822

RESUMO

In vivo measurements of (14)C tracer distribution have usually involved monitoring the ß(-) particles produced as (14)C decays. These particles are only detectable over short distances, limiting the use of this technique to thin plant material. In the present experiments, X-ray detectors were used to monitor the Bremsstrahlung radiation emitted since ß(-) particles were absorbed in plant tissues. Bremsstrahlung radiation is detectable through larger tissue depths. The aim of these experiments was to demonstrate the Bremsstrahlung method by monitoring in vivo tracer-labelled photosynthate partitioning in small kiwifruit (Actinidia arguta (Siebold & Zucc.) Planch. ex Miq.) plants in response to root pruning. A source shoot, consisting of four leaves, was pulse labelled with (14)CO(2). Detectors monitored import into a fruit and the root system, and export from a source leaf. Repeat pulse labelling enabled the comparison of pre- and post-treatment observations within an individual plant. Diurnal trends were observed in the distribution of tracer, with leaf export reduced at night. Tracer accumulated in the roots declined after approximately 48 h, which may have resulted from export of (14)C from the roots in carbon skeletons. Cutting off half the roots did not affect tracer distribution to the remaining half. Tracer distribution to the fruit was increased after root pruning, demonstrating the higher competitive strength of the fruit than the roots for carbohydrate supply. Increased partitioning to the fruit following root pruning has also been demonstrated in kiwifruit field trials.


Assuntos
Actinidia/metabolismo , Metabolismo dos Carboidratos , Raízes de Plantas/metabolismo , Monitoramento de Radiação/métodos , Partículas beta , Transporte Biológico , Dióxido de Carbono/metabolismo , Radioisótopos de Carbono/análise , Ritmo Circadiano , Frutas/metabolismo , Folhas de Planta/metabolismo , Brotos de Planta/metabolismo , Traçadores Radioativos , Raios X
10.
Nat Commun ; 13(1): 7461, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36460659

RESUMO

There is no safe level of exposure to inorganic arsenic or uranium, yet recent studies identified sociodemographic and regional inequalities in concentrations of these frequently detected contaminants in public water systems across the US. We analyze the county-level association between racial/ethnic composition and public water arsenic and uranium concentrations from 2000-2011 using geospatial models. We find that higher proportions of Hispanic/Latino and American Indian/Alaskan Native residents are associated with significantly higher arsenic and uranium concentrations. These associations differ in magnitude and direction across regions; higher proportions of non-Hispanic Black residents are associated with higher arsenic and uranium in regions where concentrations of these contaminants are high. The findings from this nationwide geospatial analysis identifying racial/ethnic inequalities in arsenic and uranium concentrations in public drinking water across the US can advance environmental justice initiatives by informing regulatory action and financial and technical support to protect communities of color.


Assuntos
Arsênio , Água Potável , Urânio , Humanos , Arsênio/toxicidade , Grupos Raciais , Etnicidade
11.
Exp Dermatol ; 20(6): 514-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21585555

RESUMO

Alterations in the protein tyrosine phosphatase N22 (PTPN22) gene affect the threshold for lymphocyte activation. The PTPN22 1858T polymorphism leads to uninhibited T-cell receptor cascade propagation. An elevated PTPN22 1858C/T genotype frequency has been correlated with several autoimmune disorders which have T-cell and humoral components. However, a recent Tunisian report demonstrated no association between PTPN22 1858T and patients with Pemphigus vulgaris (PV), an autoantibody-associated blistering disorder. Because PTPN22 1858T allele frequency is known to vary across ethnic populations, we conducted a case-control study investigating the relationship between PTPN22 1858T and PV in North American patients of either Ashkenazi Jewish or Caucasian (non-Ashkenazi) decent. Participant genotype was determined in 102 PV patients and 102 healthy controls by restriction fragment length polymorphism-polymerase chain reaction genotyping. Relationships were calculated using Fisher's exact tests and chi-squared tests. We report that the PTPN22 1858C/T genotype is not significantly associated with PV in either Caucasians (P = 0.83) or Ashkenazi Jews (P = 0.60). Further stratification of the patient population by gender, age of disease onset, HLA-type, family history of autoimmune disease, history of anti-desmoglein (anti-Dsg) 3 or anti-Dsg1 antibody response, history of lesion morphology, and disease duration did not uncover significant associations between the PTPN22 1858T allele and PV subgroups. Our data indicate that the PTPN22 1858T mutation is not associated with PV in the North American population. We do observe an elevation of PTPN22 1858C/T genotype frequency in male PV patients. Further investigation will be required to determine if this trend reaches significance in larger studies.


Assuntos
Pênfigo/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Alelos , Autoanticorpos/sangue , Doenças Autoimunes/genética , Sequência de Bases , Estudos de Casos e Controles , Primers do DNA/genética , Desmogleína 1/imunologia , Desmogleína 3/imunologia , Feminino , Frequência do Gene , Genes MHC da Classe II , Predisposição Genética para Doença , Humanos , Judeus/genética , Masculino , Pessoa de Meia-Idade , América do Norte , Pênfigo/enzimologia , Pênfigo/imunologia , Fatores de Risco , População Branca/genética
12.
Crit Care Explor ; 3(7): e0499, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34345825

RESUMO

OBJECTIVES: Overutilization of laboratory services is now recognized as harmful to patients and wasteful. In fact, the American Board of Internal Medicine's Choosing Wisely campaign recommends against ordering routine testing that does not answer a clinical question. Per peer benchmarking, our institution as a whole occupied an extreme outlier position at the 100th percentile for laboratory utilization. We sought to address this problem starting in our medical ICUs with a quality improvement project. DESIGN: Quality improvement project using the design, measure, analyze, improve, and control process. The primary endpoint was a sustained reduction in laboratory utilization. Counterbalance metrics were also followed, and these included mortality, renal replacement therapy initiation rates, stat laboratory orders, and central catheter-associated blood stream infections. SETTING: The medical ICU at the Ohio State University Medical Center. PATIENTS: All patients admitted to the medical ICU from March 2019 to March 2020. INTERVENTIONS: Root causes were identified and addressed with the implementation of a wide range of interventions involving a multidisciplinary team led by trainee physicians. MEASUREMENTS AND MAIN RESULTS: There was a sustained 20% reduction in the number of tests performed per patient day, with no change in the counterbalance metrics. CONCLUSIONS: Trainees can affect positive change in the culture and processes at their institutions to safely reduce laboratory utilization.

13.
J Biol Chem ; 284(31): 20540-7, 2009 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-19487701

RESUMO

Little has been known about Tlr13 (Toll-like receptor 13), a novel member of the Toll-like receptor family. To elucidate the molecular basis of murine Tlr13 gene expression, the activity of the Tlr13 gene promoter was characterized. Reporter gene analysis and electrophoretic mobility shift assays demonstrated that Tlr13 gene transcription was regulated through three cis-acting elements that interacted with the Ets2, Sp1, and PU.1 transcription factors. Furthermore, our work suggests that these transcription factors may cooperate, culminating in maximal transcription of the Tlr13 gene. In contrast, NF-kappaB appeared to act as an inhibitor of Tlr13 transcription. Overexpression of Ets2 caused a strong increase in the transcriptional activity of the Tlr13 promoter; however, overexpression of NF-kappaB p65 dramatically inhibited it. Additionally, interferon-beta is capable of acting Tlr13 transcription, but the activated signaling of lipopolysaccharide/TLR4 and peptidoglycan/TLR2 strongly inhibited the Tlr13 gene promoter. Thus, these findings reveal the mechanism of Tlr13 gene regulation, thereby providing insight into the function of Tlr13 in the immune response to pathogen.


Assuntos
Regulação da Expressão Gênica , Receptores Toll-Like/genética , Transcrição Gênica , Região 5'-Flanqueadora/genética , Animais , Sequência de Bases , Linhagem Celular , Clonagem Molecular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Modelos Genéticos , Dados de Sequência Molecular , Peptidoglicano/farmacologia , Poli I-C/farmacologia , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Proteína Proto-Oncogênica c-ets-2/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sequência de DNA , Receptores Toll-Like/metabolismo , Transativadores/metabolismo , Sítio de Iniciação de Transcrição , Transcrição Gênica/efeitos dos fármacos
14.
J Clin Gastroenterol ; 44(3): 195-9, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19609217

RESUMO

BACKGROUND: Metastatic carcinoid tumors (MCTs), an important subgroup of neuroendocrine tumors, occur infrequently and often have an indolent course, limiting data on long-term treatment outcomes. We aimed to assess treatment trends at a single center over time and the impact on the outcome. STUDY: Patients diagnosed with carcinoid tumors in the North West Adelaide Health Service between January 1, 1985 and March 1, 2007 were identified from the South Australian Cancer Registry. RESULTS: We identified 92 patients with carcinoid tumors; 49 had MCT. Although treatment options increased over time, the most significant change was to access octreotide therapy, with 24 receiving long-acting somatostatin analogs. Survival improved over time and the median overall survival for patients receiving long-acting somatostatin analogs was 112 months compared with 53 months for those who did not (P=0.021, hazard ratio: 2.46). Ten year survival was 40% and 22%, respectively. About 75% of evaluable patients had a biochemical response to initial therapy and a measurable response occurred in 3 of 24 (13%) patients. CONCLUSIONS: This single center experience has provided insight into current treatment options for MCT, and suggests the use of long-acting somatostatin analogs may impact on disease control and survival. However, the uptake of other treatment options seems limited and there is a need for agents that target tumor progression.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Tumor Carcinoide/terapia , Octreotida/uso terapêutico , Idoso , Tumor Carcinoide/mortalidade , Tumor Carcinoide/patologia , Bases de Dados Factuais , Progressão da Doença , Feminino , Humanos , Masculino , Metástase Neoplásica , Sistema de Registros , Estudos Retrospectivos , Somatostatina/análogos & derivados , Somatostatina/uso terapêutico , Austrália do Sul , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
16.
BMJ Case Rep ; 13(12)2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33334744

RESUMO

Myxopapillary ependymoma (MPE) is a rare glial tumour mainly located in the areas of the conus medullaris, cauda equina and filum terminale of the spinal cord. Ectopic MPE tends to behave more aggressively and distant metastases are often seen. Unfortunately, no standard treatment options are established as only small series of treated patients and a few reported cases are available in the literature. We report the case of a 25-year-old woman who was initially diagnosed with a metastatic MPE, with multiple bilateral lung metastases. She was treated with an investigational monoclonal antibody antiprogrammed cell death protein 1, called tislelizumab (BGB-A317), following surgical resection of the perisacral primary mass. The response was long-lasting and side effects nil. Immunotherapy is a treatment modality to be considered in patients with rare tumours.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Drogas em Investigação/uso terapêutico , Ependimoma/terapia , Neoplasias Pulmonares/terapia , Neoplasias da Medula Espinal/terapia , Biópsia com Agulha de Grande Calibre , Quimioterapia Adjuvante/métodos , Ependimoma/complicações , Ependimoma/diagnóstico , Ependimoma/secundário , Feminino , Humanos , Dor Lombar/etiologia , Dor Lombar/terapia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Imageamento por Ressonância Magnética , Invasividade Neoplásica , Sacro/diagnóstico por imagem , Sacro/patologia , Sacro/cirurgia , Medula Espinal/patologia , Medula Espinal/cirurgia , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
17.
Public Health Rep ; 123 Suppl 3: 115-25, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19166095

RESUMO

OBJECTIVES: From 2001 through 2005, African Americans accounted for the largest percentage of new cases of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome (AIDS) in all age categories, especially among people aged 13 to 24 years. Although students attending historically black colleges and universities (HBCUs) report many of the behaviors that promote HIV transmission, their risk behaviors and HIV testing practices have not been well-characterized. We compared the demographic and behavioral characteristics of people who have been previously tested for HIV with those of people tested for the first time in this demonstration project to increase HIV testing at HBCUs. METHODS: The Centers for Disease Control and Prevention and collaborating partners conducted rapid HIV testing and behavioral surveys at HBCUs in Arkansas, Georgia, Mississippi, and Washington, D.C., from January 2005 to April 2007. We recruited a convenience sample of students and community members at different campus venues including student health centers, dormitories, and student activity centers. RESULTS: Our analysis included 5,291 people, 42% of whom reported they had never been tested for HIV. People who had been tested in the past were more likely to be older, believe they were at high risk for infection, have visited a health-care facility, and report behaviors that increased their risk of HIV infection. CONCLUSION: Respondents who believed they were at increased risk for HIV infection or reported behaviors that increased their risk for infection were more likely to have been tested for HIV. Future research should compare actual vs. perceived risk for HIV infection and contrast how each impacts HIV testing.


Assuntos
Sorodiagnóstico da AIDS/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Infecções por HIV/epidemiologia , Comportamentos Relacionados com a Saúde , Assunção de Riscos , Comportamento Sexual/estatística & dados numéricos , Estudantes/estatística & dados numéricos , Universidades/estatística & dados numéricos , Adolescente , Adulto , Centers for Disease Control and Prevention, U.S. , Aconselhamento Diretivo , Feminino , Infecções por HIV/transmissão , Humanos , Masculino , Fatores de Risco , Estados Unidos/epidemiologia , Adulto Jovem
18.
Int J Behav Med ; 15(4): 319-27, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19005932

RESUMO

BACKGROUND: Relatively few studies have examined positive character traits that are associated with lower HIV/STD risks. PURPOSE: In the present study, the relationships of character strengths with sexual behaviors and attitudes were assessed among 383 African-American adolescents. METHOD: Character strengths were measured using the Values in Action Inventory of Strengths. Because the strengths were highly inter-correlated, stepwise discriminant function analyses were utilized to assess their independent associations with sexual behaviors and attitudes. RESULTS: Greater Love of Learning was related to self-reported abstinence from sexual intercourse for boys and self-reported abstinence from drug use for boys and girls. Greater Love of Learning and Curiosity were related to the belief in no premarital sex for boys, whereas only Curiosity was significant for girls. Prudence was related to reported abstinence from sexual intimacy (e.g., touching or kissing). Judgment was related to sexual initiation efficacy for girls and boys, whereas Leadership was only significant for girls. CONCLUSIONS: The findings suggest that character strengths may be associated with lower levels of sexual behaviors and sex-related beliefs among a sample of African-American adolescents.


Assuntos
Negro ou Afro-Americano/psicologia , Caráter , Conhecimentos, Atitudes e Prática em Saúde , Psicologia do Adolescente , Comportamento Sexual , Adolescente , Criança , Cultura , Feminino , Identidade de Gênero , Inquéritos Epidemiológicos , Humanos , Individualidade , Controle Interno-Externo , Julgamento , Liderança , Aprendizagem , Masculino , Inventário de Personalidade/estatística & dados numéricos , Psicometria , Abstinência Sexual/etnologia , Abstinência Sexual/psicologia , Espiritualidade , Transtornos Relacionados ao Uso de Substâncias/etnologia , Transtornos Relacionados ao Uso de Substâncias/psicologia
19.
Leuk Lymphoma ; 48(9): 1702-11, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17786705

RESUMO

Idiopathic hyperammonemic encephalopathy is an uncommon but frequently fatal complication of chemotherapy. It is characterised by abrupt alteration in mental status with markedly elevated plasma ammonia levels in the absence of obvious liver disease or any other identifiable cause, and frequently results in intractable coma and death. It usually occurs in patients with haematologic malignancies during the period of neutropenia following cytoreductive therapy or bone marrow transplantation, and in solid organ malignancies treated with 5-fluorouracil. Although the aetiology of this syndrome is yet to be determined, it appears to be multi-factorial in nature. Optimal management remains to be formally established, and the critical step is increased awareness of the syndrome by measurement of plasma ammonium levels in patients with neurological symptoms, leading to early diagnosis and the prompt implementation of therapy.


Assuntos
Antineoplásicos/efeitos adversos , Encefalopatias/induzido quimicamente , Hiperamonemia/induzido quimicamente , Transplante de Medula Óssea/efeitos adversos , Encefalopatias/diagnóstico , Encefalopatias/terapia , Diagnóstico Diferencial , Humanos , Hiperamonemia/diagnóstico , Hiperamonemia/terapia , Diálise Renal
20.
J Pain Symptom Manage ; 47(6): 1019-27, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24095286

RESUMO

CONTEXT: Palliative care consult services have emerged as an excellent resource for physicians seeking help with patients' symptoms. Symptoms include those of a psychiatric nature (e.g., depression, anxiety, delirium); however, little information is known about whether palliative care services include psychiatric input as part of multidisciplinary teams. OBJECTIVES: To explore 1) the current level of collaboration between psychiatrists and palliative care consult services across the U.S. and 2) the factors that support or restrict such involvement. METHODS: A national survey was developed and distributed electronically to program directors identified in the National Palliative Care Registry maintained by the Center to Advance Palliative Care. Analyses examined trends in psychiatry involvement with hospital-based palliative care teams. RESULTS: The survey had a 59% response rate, with final analyses including surveys completed by 260 palliative care program directors (67% inclusion rate from total respondents). Seventy-two percent of respondents reported some form of involvement with a psychiatrist on their palliative care service, with only 10% of those identifying a psychiatrist as a full- or part-time member of the team. Most respondents reported that they would like psychiatrists to be more involved with the palliative care services (71%). Secondary analyses of qualitative responses identified common impediments to increased psychiatry involvement, which included financial constraints, provider interest, and perceived disciplinary disconnect. CONCLUSION: There are shared objectives between psychiatry and palliative care; however, currently, co-involvement on treatment teams is quite limited. Future research is needed to identify ways to facilitate the interface of palliative care and psychiatry.


Assuntos
Cuidados Paliativos , Psiquiatria , Encaminhamento e Consulta , Adulto , Idoso , Feminino , Humanos , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Equipe de Assistência ao Paciente , Sistema de Registros , Estados Unidos
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