RESUMO
BACKGROUND: Thyroid nodules are common in clinical practice, and it is important to distinguish benign nodules, the vast majority, from malignant ones. Non-diagnostic (ND) samples have the potential to delay or mis-diagnose or lead to unnecessary surgeries, and it is important to examine what factors influence the ND rate. Prior literature has suggested that the impact of bedside cytology on ND rate is dependent on the initial adequacy rate, whereby higher ND rates benefit most from bedside cytology. We aim to compare the impact of bedside adequacy review between specialist groups who perform high volume thyroid biopsies with low initial ND rates. METHODS: We reviewed the cytopathology results of 1975 thyroid nodule FNAs performed between January 1, 2017 to December 31, 2017 in a multi-centre Canadian city, and the corresponding histopathology reports of 340 resected nodules. Descriptive variables were used to describe the data along with chi-squared testing and univariate logistic regression. RESULTS: The FNA biopsies were performed by three different speciality groups, which differed by procedural volume: radiology performed the most at 1171, pathology performed 655 and surgery performed 103. We could not define the operator for 45 of the nodules. The ND rate was lowest in the speciality groups with highest procedural volume, 3.4 % in pathology and 8.3 % in radiology, compared to 37.9 % in surgery (p < 0.001). Completion of bedside cytology rapid onsite evaluation (ROSE) significantly reduced the ND rate from 16.7 to 4.2 % for all samples (p < 0.001). When ROSE was compared with non-ROSE within a high procedural group (radiology), it further reduced the ND rate from 12.5 to 5.1 % (p < 0.001). Of the 340 resected nodules, 10.7 % (18) were in the ND category, of which 28 % (5/18) of these were found to be malignant (4 papillary carcinoma and 1 lymphoma). CONCLUSIONS: The results from this study demonstrate that thyroid FNAs performed with bedside ROSE can significantly reduce the ND rate compared with non-ROSE, even in experienced groups with low initial ND rates. It is therefore imperative that care providers managing patients with thyroid nodules ensure that thyroid FNAs are referred to specialized individuals/groups who do high volume, and ideally with the use of bedside ROSE, whether provided by a cytotechnologist or a pathologist.
RESUMO
Thyroid cancer is the most common type of endocrine malignancy. Cornerstones of thyroid cancer treatment include surgery, radioactive iodine ablation, and thyroid stimulating hormone suppression. The National Comprehensive Cancer Network guidelines recommend two tyrosine kinase inhibitors for thyroid cancer patients who are non-responsive to iodine: sorafenib and lenvatinib. Another oral kinase inhibitor, regorafenib, is not considered standard of care treatment for differentiated thyroid cancer. The chemical structures of regorafenib and sorafenib differ by a single fluorine atom. Given the significant improvement in progression-free survival (PFS) of sorafenib compared to placebo demonstrated in the phase 3 DECISION trial, we report on a patient with iodine-refractory follicular thyroid cancer treated with regorafenib as part of a phase 1 clinical trial. A 75 year old woman was diagnosed with follicular thyroid carcinoma in 2006 and initiated on treatment with regorafenib in 2011. She has completed 76 cycles with stable disease and pulmonary metastases 34% smaller than baseline.
RESUMO
Many neuromuscular diseases (NMD) result in muscle weakness, immobility and greater fracture risk. The objective of this study is to determine the fracture risk of adult patients at a multidisciplinary NMD clinic. Fracture risk was calculated using the Fracture Risk Assessment Tool, the presence of osteoporosis was quantified using bone densitometry and contributing co-morbidities were screened through serum markers. Of the 36 patients studied, 47% were found to be of moderate and high fracture risk. Two thirds of these patients had not been previously screened or treated for osteoporosis. These findings suggest that NMD patients warrant routine screening for osteoporosis and early treatment to reduce fragility fracture.
Assuntos
Fraturas Ósseas/epidemiologia , Doenças Neuromusculares/epidemiologia , Osteoporose/epidemiologia , Adulto , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , RiscoRESUMO
PURPOSE OF THE STUDY: To compare efficacy of thyroid remnant ablation using 30 mCi or 50 mCi 131-I in papillary thyroid cancer patients. MATERIALS AND METHODS: Five hundred and fifteen consecutive patients with Tumor-Node-Metastasis (TNM) stages T1-T3 N1/N0/NX receiving either 30 mCi or 50 mCi I-131 were analyzed for the effectiveness of remnant ablation using rhTSH-stimulated serum thyroglobulin. One hundred and five consecutive patients receiving 100 mCi I-131 were analyzed for the incidence of radiation thyroiditis and sialadenitis. RESULTS AND CONCLUSIONS: Doses of 30 mCi and 50 mCi were equally effective for low- and moderate-risk disease but 30 mCi was less effective for T1T2NX disease, and 50 mCi was less effective for T3 compared to T1T2 disease. Low dose radiation hypersensitivity or unknown more extensive disease may have accounted for observed differences. Radiation thyroiditis and sialadenitis were more common in a comparison series of 100 mCi dose compared to 30 mCi, but not more common than in 50 mCi doses.
Assuntos
Técnicas de Ablação/efeitos adversos , Técnicas de Ablação/métodos , Carcinoma Papilar/radioterapia , Radioisótopos do Iodo/farmacologia , Avaliação de Resultados em Cuidados de Saúde , Sialadenite/etiologia , Neoplasias da Glândula Tireoide/radioterapia , Tireoidite/etiologia , Adulto , Humanos , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/efeitos adversos , Estadiamento de Neoplasias , Estudos Retrospectivos , Câncer Papilífero da TireoideRESUMO
PURPOSE: Steroids, inhaled and systemic, are used to treat airway inflammation in patients with asthma; however, steroids are recognized to cause a number of side effects, including osteoporosis. We evaluated the prevalence of osteopenia/osteoporosis in patients with moderate-severe asthma managed through the Edmonton Regional Severe Asthma Centre. METHODS: We performed a retrospective chart review and analyzed 57 charts on patients with moderate-severe asthma followed through the specialty clinic, and recorded their bone mineral density (BMD). Steroid use was reviewed and the frequency of osteopenia/osteoporosis was compared in patients requiring continuous systemic steroids (Group 1, n=15), intermittent systemic steroids (Group 2, n=15) or inhaled steroids only (Group 3, n=27). RESULTS: The mean age (mean±SD) was 50±14.8 years. Cumulative systemic steroid dose of prednisone equivalent was higher in Group 1 (12.5 mg/day) than Group 2 (3.2 mg/day) (p=0.002). The frequency of osteopenia / osteoporosis was not significantly different between patients in Group 1(67%) and Group 2 (53%, p=0.46) but was significantly greater in patients from Group 1 in comparison with Group 3 (33%, p=0.038). CONCLUSION: Patients with moderate-severe asthma have a high prevalence of reduced bone density. Many patients treated with intermittent systemic steroids for exacerbations, or who were stable on inhaled steroids, had either osteopenia or osteoporosis before the age of 50. National and international osteoporosis guidelines should emphasize earlier screening for asthma patients; and increase awareness of the detrimental effects of short-term systemic steroids and inhaled steroids on BMD, especially when started at an early age and in northern climates.
Assuntos
Asma/complicações , Doenças Ósseas Metabólicas/etiologia , Osteoporose/etiologia , Alberta/epidemiologia , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Densidade Óssea , Doenças Ósseas Metabólicas/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: In addition to increasing the risk of adverse birth outcomes, diabetes in pregnancy is thought to be an important driver of the epidemic of type 2 diabetes affecting Canada's First Nations population. The relative contributions of gestational diabetes mellitus (GDM) and pre-existing diabetes are not well understood. We generated a comprehensive epidemiological profile of diabetes in pregnancy over a 10-year period among the First Nations population of Alberta, Canada. METHODS: De-identified administrative data for 427,058 delivery records were obtained for the years 2000-2009. Pregnancy risk factors and delivery outcomes were described and compared by ethnicity (First Nations vs. non-First Nations) and diabetes status. Age-adjusted prevalence values for GDM and pre-existing diabetes were calculated and were compared by ethnicity. Longitudinal changes over time were also examined. Predictors were explored using logistic regression analysis. RESULTS: First Nations women had more antenatal risk factors and adverse infant outcomes that were compounded by diabetes. First Nations descent was an independent predictor of diabetes in pregnancy (p < 0.001). GDM prevalence was significantly higher among First Nations (6.1%) compared to non-First Nations women (3.8%; p < 0.001), but prevalence values increased significantly over time only in non-First Nations women (4.5 average annual percent change; p < 0.05). The prevalence of pre-existing diabetes was stable over time in both groups, but First Nations women experienced a 2.5-fold higher overall prevalence compared with non-First Nations women (1.5% vs. 0.6%, respectively; p < 0.001). CONCLUSIONS: Although First Nations women experience a higher overall prevalence of diabetes in pregnancy, the lack of increase in the prevalence over time is encouraging. However, because high-risk pregnancies and poor outcomes are more common among First Nations women, particularly those with diabetes, strategies to improve perinatal care must be implemented.
Assuntos
Diabetes Gestacional/etnologia , Gravidez de Alto Risco , Grupos Raciais , Medição de Risco/métodos , Adulto , Alberta/epidemiologia , Glicemia/metabolismo , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Feminino , Humanos , Incidência , Recém-Nascido , Gravidez , Resultado da Gravidez , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
INTRODUCTION: The study was aimed to determine the response and predictive risk factors of differentiated thyroid cancer (DTC) with measurable (0.4-2.0 µg/L) stimulated serum thyroglobulin (sTg) during the 10-24 months after radioiodine remnant ablation (RRA) and their long-term outcomes. METHODS: Out of 839 retrospectively reviewed patients, 95 eligible DTC patients were included. Patients were classified as having incomplete response or no evidence of disease (NED). The sTg cut-off values with highest predicted accuracy for incomplete response at 10-24 months were calculated with receiver operator characteristics curve analysis. RESULTS AND CONCLUSION: At 10-24 months after RRA, incomplete response was identified in 54 patients (57%) and 38/54 (70.4%) patients were found with structural evidence of disease. The remaining 16 patients (29.6%) had biochemical evidence of disease without structural evidence of disease. Forty-one patients (43%) were classified as having NED at 10-24 months after RRA and 27 patients (66%) did not receive further radioactive iodine (RAI) therapy and remained disease free at median follow-up of 6.5 years. Fourteen patients received second RAI treatment after 6 months and before the 10-24 months assessment time point. Of these, 2 had persistent tumor 6 years later. The sTg >0.6 µg/L at 6-10 months after RRA had optimal sensitivity (83.3%), specificity (56%) and negative predictive value (72%) of detecting incomplete response at 10-24 months after RRA. A total of 23/43 patients in the American Thyroid Association low-risk category had incomplete response after first RRA and 5/23 (21.7%) had recurrent/persistent disease at long-term follow-up.
Assuntos
Recidiva Local de Neoplasia/diagnóstico , Tolerância a Radiação , Compostos Radiofarmacêuticos/uso terapêutico , Tireoglobulina/sangue , Glândula Tireoide/efeitos da radiação , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Terapia Combinada , Feminino , Seguimentos , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Neoplasia Residual , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tireoglobulina/metabolismo , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Carga Tumoral/efeitos da radiação , Adulto JovemRESUMO
BACKGROUND: Opioid analgesia impairs gonadal function in men and women, but the correlation with symptoms and hormonal measurements of hypogonadism is not well established. OBJECTIVE: To determine the frequency of impaired gonadal function in men and women using opioids for chronic pain, and to determine the correlation of symptoms with hormonal measurements of gonadal function. METHODS: A prospective study of patients attending a multidisciplinary pain clinic was conducted. A total of 65 women (47 opioid users and 18 nonopioid analgesic controls) and 32 men (26 opioid users and six controls) were enrolled. Histories of sexual dysfunction and hormonal testing (men: total testosterone [TT], free testosterone [FT], prolactin and luteinizing hormone; women: FT, TT, prolactin, dehydroepiandrosterone sulphate, sex hormone- binding globulin, progesterone, luteinizing hormone and follicle- stimulating hormone, and estradiol) were obtained. RESULTS: In men, a low FT level was more common in opioid users (20/26; P=0.04). In men with abnormal hormone levels, there was no difference in the frequency of sexual dysfunction compared with men with normal hormone levels, and no difference in the frequency of opioid versus nonopioid use. In women, opioid users had lower FT levels (P=0.02). Low dehydroepiandrosterone sulphate was more frequent in women on opioids (P=0.03) in the menopausal group only (P=0.046). Premenopausal women taking opioids more frequently had a low TT level (P=0.03). The frequency of female sexual dysfunction was the same in opioid users (32/47) and controls (13/18; P=0.75), and also did not relate to any hormone abnormality. DISCUSSION: Men taking opioids had lower FT and higher prolactin levels, and women taking opioids had lower FT levels. Frequency of sexual dysfunction did not correlate with hormone levels in either men or women taking opioids. CONCLUSION: Opioids frequently cause low FT levels in men, but there is no relationship between abnormal hormone levels and symptoms of sexual dysfunction. Therefore, all men should be screened for low FT levels. Women on opioids had lower FT levels, but this did not correlate with sexual dysfunction symptoms. Therefore, measurements of FT or other hormones were not considered to be useful in women.
Assuntos
Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , Hormônios Gonadais/metabolismo , Disfunções Sexuais Psicogênicas/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Hormônios Hipofisários/metabolismo , Prolactina , Estudos Prospectivos , Fatores Sexuais , Estatística como AssuntoRESUMO
OBJECTIVE: To estimate prevalence of rectovaginal colonization by Staphylococcus aureus among pregnant women with group B streptococcus (GBS) screening results and its association with maternal and infant outcomes. STUDY DESIGN: Cultures that detected both group B streptococcus (GBS) and S. aureus were obtained at > or = 35 weeks of gestation. Computerized database search and chart review determined invasive neonatal infection and maternal outcomes at the time of delivery through 6 months postpartum. RESULTS: A total of 6,626 GBS screening cultures met study criteria, and 769 (11.6%) GBS isolates and 67 (1.0%) S. aureus were identified. No maternal S. aureus-related outcomes were found. The rate of maternal methicillin-resistant S. aureus colonization was 0.1% (7 in 6,626). GBS-positive patients were twice as likely to be colonized with methicillin-susceptible S. aureus than GBS-negative patients. GBS-positive culture rates differed significantly by primary language: Spanish 10.0%, English 13.7%, Russian 26.9%, Cantonese 13.2%, Mandarin 11.5%, Arabic 15.9%, and other 17.8%. CONCLUSION: In our population, S. aureus colonization percentage (1.0%) was lower than the 7.5-8.2% reported by other medical centers, as was overall GBS carriage rate. S. aureus did not predispose to maternal or infant morbidity or mortality up to 6 months postpartum.
Assuntos
Complicações Infecciosas na Gravidez/epidemiologia , Reto , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus , Vagina , Adulto , Portador Sadio/diagnóstico , Portador Sadio/epidemiologia , Portador Sadio/terapia , Feminino , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/terapia , Diagnóstico Pré-Natal , Prevalência , Estudos Retrospectivos , Infecções Estafilocócicas/terapia , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/terapia , Streptococcus agalactiae , Adulto JovemRESUMO
Proteomics were performed using highly (99.99%) purified cytotrophoblasts from six normal and six pre-eclamptic placentas. Eleven proteins were found which decreased in pre-eclampsia (actin, glutathione S-transferase, peroxiredoxin 6, aldose reductase, heat shock protein 60 (Hsp60), two molecular forms of heat shock protein 70 (Hsp70) ß-tubulin, subunit proteasome, ezrin, protein disulfide isomerase, and phosphoglycerate mutase 1). Only one protein, α-2-HS-glycoprotein (fetuin), was found to increase its expression. Western blots of actin, Hsp70, ezrin, and glutatione S-transferase confirmed decrease in protein expression. Many of the proteins that decreased are consistent with a state of oxidative stress in the pre-eclamptic placenta and a decreased cytotrophoblast defense against and response to oxidative stress.
Assuntos
Estresse Oxidativo , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Proteômica , Trofoblastos/metabolismo , Western Blotting , Eletroforese em Gel Bidimensional , Feminino , Fetuínas/química , Fetuínas/metabolismo , Humanos , Gravidez , Trofoblastos/química , Regulação para CimaRESUMO
The tachykinin neurokinin B which is encoded on the tachykinin 3 precursor, has prominent roles in both neuronal and endocrine systems, yet little is known about its evolution, potential splice variants and the manner in which it is processed. Here, we deduce the diversity within the vertebrate tachykinin 3 precursors, and identify novel tachykinin 3 splice variants and precursors. A total of 35 different tachykinin 3 precursors were identified in mammals, birds and reptiles. Nine additional alternatively spliced tachykinin 3 mRNA transcripts were also discovered in humans leading to the formation of three tachykinin 3 precursors (named alpha, beta and gamma tachykinin 3), but no novel tachykinin. gamma tachykinin 3, albeit rarer, was not found to encode neurokinin B. Differential processing of the tachykinin 3 precursor in the human placenta leads to the formation of potential NH2-terminally extended forms of neurokinin B. Moreover, we found increased proteolytic cleavage of the tachykinin 3 precursor during the pregnancy syndrome of pre-eclampsia. We have established neurokinin B to be an evolutionarily conserved peptide, nonetheless the significance of the three different tachykinin 3 precursors is not clear, but could represent an evolutionarily redundant splicing mechanism once employed by an ancestral gene that encoded two tachykinins. Our results indicate that differential mRNA splicing and precursor processing is likely to play an important role in differentiating the actions of the tachykinin 3 gene products in both neuronal and endocrine tissues.
Assuntos
Neurocinina B/genética , Sistemas Neurossecretores/metabolismo , Splicing de RNA/genética , RNA Mensageiro/genética , Sequência de Aminoácidos , Animais , Cromatografia em Gel , Biologia Computacional , Feminino , Humanos , Imunoensaio , Dados de Sequência Molecular , Neurocinina B/classificação , Filogenia , Reação em Cadeia da Polimerase , Pré-Eclâmpsia/genética , Gravidez , Ratos , Homologia de Sequência de Aminoácidos , Taquicininas/genéticaRESUMO
BACKGROUND: In a randomized trial of patients with hip fractures, we previously demonstrated that a hospital-based case manager could increase rates of appropriate osteoporosis treatment to 51% compared with 22% for usual care (P < .001). Alongside that trial, we conducted an economic analysis. METHODS: Patients with hip fractures were randomized to usual care (n = 110) or a case manager (n = 110) and followed up for 1 year. Time-motion studies were used to determine intervention costs. From a third-party health care payer perspective and over the patient's remaining lifetime, a Markov decision-analytic model was constructed to determine cost-effectiveness of the intervention compared with usual care. Costs and benefits were discounted at 3% and expressed in 2006 Canadian dollars. RESULTS: The intervention cost CaD $56 per patient. Compared with usual care, the intervention strategy was dominant: for every 100 patients case managed, 6 fractures (4 hip fractures) were prevented, 4 quality-adjusted life-years were gained, and CaD $260 000 was saved by the health care system. Irrespective of the number of patients case managed, the intervention reached a break-even threshold within 2 years. The intervention dominated usual care over the entire spectrum of 1-way sensitivity analyses and was cost-saving in 82% of probabilistic model simulations. CONCLUSIONS: Compared with usual care, we found that using a case manager for patients with hip fractures increased rates of appropriate osteoporosis treatment. The intervention dominated usual care, and the analysis suggests that systems implementing an intervention similar to ours should expect to see a reduction in fractures, gains in life expectancy, and substantial cost savings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00175175.
Assuntos
Administração de Caso/economia , Redução de Custos , Custos de Cuidados de Saúde , Fraturas do Quadril/cirurgia , Osteoporose/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/fisiologia , Análise Custo-Benefício , Difosfonatos/uso terapêutico , Feminino , Seguimentos , Fixação Intramedular de Fraturas/economia , Fixação Intramedular de Fraturas/métodos , Fraturas do Quadril/diagnóstico por imagem , Fraturas do Quadril/economia , Fraturas do Quadril/mortalidade , Humanos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico , Probabilidade , Qualidade de Vida , Radiografia , Valores de Referência , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: We previously demonstrated that a case manager intervention improved osteoporosis (OP) treatment within 6 months of hip fracture compared with usual care. The second phase of the randomized trial compared a less intensive intervention, facilitated bone mineral density (BMD) testing, with usual care and the case manager intervention. METHODS: We initially randomized 220 hip fracture patients to either an OP case manager intervention or usual care. After completing the original trial at 6 months postfracture, usual care patients were reallocated to facilitated BMD testing; BMD tests were arranged and results sent to primary care physicians. Main outcomes (bisphosphonate treatment, BMD tests, receipt of appropriate care) were reascertained 1 year following hip fracture and compared with outcomes achieved by the OP case manager intervention and usual care. RESULTS: Compared with usual care, facilitated BMD testing increased testing from 29% to 68% (P < 0.001), bisphosphonate use from 22% to 38% (P < 0.001), and receipt of appropriate care from 26% to 45% (P < 0.001). The more intensive (70 versus 30 minutes) and expensive ($56 versus $24 Canadian per patient) OP case manager intervention led to significantly higher bisphosphonate use (54% versus 38%; P = 0.03), receipt of appropriate care (71% versus 45%; P < 0.001), and more BMD testing (80% versus 68%; P = 0.06) than usual care followed by facilitated BMD testing. CONCLUSION: Compared with usual care, 2 different inexpensive interventions resulted in significant increases in appropriate management of OP after hip fracture. The magnitude of improvements achieved was directly related to the intensity of the interventions.
Assuntos
Densidade Óssea , Administração de Caso , Fraturas do Quadril/reabilitação , Osteoporose/tratamento farmacológico , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/uso terapêutico , Procedimentos Clínicos , Difosfonatos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de SaúdeRESUMO
Adrenomedullin is synthesized and secreted by fetoplacental tissues. Given that the placenta lacks autonomic innervation, we proposed that adrenomedullin acts locally to control blood flow in the placental vasculature through a balance of dilatory and constrictive pathways. Placental stem villous arteries (200 microm) from normotensive human pregnancies were dissected and mounted on a wire myograph. The vessels were preconstricted with the thromboxane A(2) mimetic U46619 (EC(80) concentration), and exposed to cumulative concentrations of adrenomedullin (1 x 10(-9) to 3 x 10(-7) mol/L). Adrenomedullin caused concentration-dependent vasorelaxation which, in endothelium-intact vessels, was attenuated in the presence of the nitric oxide synthase inhibitor L-NMMA. This suggested that the vasodilation was mediated, at least in part, through nitric oxide. However, removal of the endothelium did not similarly alter the response. Nor did L-NMMA have any effect in endothelium-denuded vessels. We hypothesized that adrenomedullin must induce release of both endothelium-derived relaxing (nitric oxide) and constricting factors. When we blocked the two major pathways through which adrenomedullin is known to induce vasodilation, by incubating the vessels with L-NMMA (nitric oxide synthase inhibitor) and Rp-cAMPS (cAMP-dependent protein kinase inhibitor), adrenomedullin induced concentration-dependent vasoconstriction. This was not mediated through endothelin, since addition of the non-specific endothelin receptor antagonist PD142893 failed to alter the response to adrenomedullin. We conclude that, in addition to increasing endothelial nitric oxide biosynthesis in placental stem villous arteries, adrenomedullin induces release of an endothelium-derived constricting factor.
Assuntos
Adrenomedulina/farmacologia , Artérias/efeitos dos fármacos , Endotelinas/fisiologia , Endotélio Vascular/fisiologia , Placenta/irrigação sanguínea , Vasodilatação/efeitos dos fármacos , Artérias/fisiologia , Endotelinas/metabolismo , Endotélio Vascular/metabolismo , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Placenta/efeitos dos fármacos , Vasodilatação/fisiologiaRESUMO
BACKGROUND: Patients who survive hip fracture are at high risk of recurrent fractures, but rates of osteoporosis treatment 1 year after sustaining a fracture are less than 10% to 20%. We have developed an osteoporosis case manager intervention. The case manager educated patients, arranged bone mineral density tests, provided prescriptions, and communicated with primary care physicians. The intervention was compared with usual care in a randomized controlled trial. METHODS: We recruited from all hospitals that participate in the Capital Health system (Alberta, Canada), including patients 50 years or older who had sustained a hip fracture and excluding those who were receiving osteoporosis treatment or who lived in a long-term care facility. Primary outcome was bisphosphonate therapy 6 months after fracture; secondary outcomes included bone mineral density testing, appropriate care (bone mineral density testing and treatment if bone mass was low), and intervention costs. RESULTS: We screened 2219 patients and allocated 220, as follows: 110 to the intervention group and 110 to the control group. Median age was 74 years, 60% were women, and 37% reported having had previous fractures. Six months after hip fracture, 56 patients in the intervention group (51%) were receiving bisphosphonate therapy compared with 24 patients in the control group (22%) (adjusted odds ratio, 4.7; 95% confidence interval, 2.4-8.9; P < .001). Bone mineral density tests were performed in 88 patients in the intervention group (80%) vs 32 patients in the control group (29%) (P < .001). Of the 120 patients who underwent bone mineral density testing, 25 (21%) had normal bone mass. Patients in the intervention group were more likely to receive appropriate care than were patients in the control group (67% vs 26%; P < .001). The average intervention cost was $50.00 per patient. CONCLUSION: For a modest cost, a case manager was able to substantially increase rates of osteoporosis treatment in a vulnerable elderly population at high risk of future fractures.
Assuntos
Administração de Caso , Fraturas do Quadril , Osteoporose/prevenção & controle , Idoso , Alberta , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Qualidade da Assistência à Saúde , Resultado do TratamentoRESUMO
The in vivo cardiovascular effects of acutely administered neurokinin B (NKB) have been attributed both to direct effects on vascular tone and to indirect effects on central neuroendocrine control of the circulation. We proposed: 1) that a modest long-term increase in plasma NKB levels would decrease mean arterial pressure (MAP) due to attenuated peripheral vascular tone, and 2) that chronic high-dose NKB would increase MAP, due to increased sympathetic outflow which would override the peripheral vasodilation. We examined the in vivo and in vitro cardiovascular effects of chronic peripheral NKB. Low- (1.8 nmol/h) or high- (20 nmol/h) dose NKB was infused into conscious female rats bearing telemetric pressure transducers. MAP, heart rate (HR) and the pressor responses to I.V. phenylephrine (PE, 8 microg) and angiotensin II (Ang II, 150 ng) were measured. Concentration-response curves of small mesenteric arteries were constructed to PE using wire myography. Low-dose NKB reduced basal MAP (88+/-2 mm Hg to 83+/-2 mm Hg), did not affect resting HR, reduced the pressor responses to PE, and attenuated the maximal constriction of mesenteric arteries to PE and KCl. By contrast, high-dose NKB increased basal MAP (86+/-1 mm Hg to 89+/-1 mm Hg), increased HR (350+/-3 beats/min to 371+/-3 beats/min), increased the pressor responses to Ang II and, contrary to our hypothesis, increased the maximum contractile responses of mesenteric arteries to PE and KCl. The cardiovascular effects of NKB are thus dose-dependent: whereas chronic low-dose NKB directly modulates vascular tone to reduce blood pressure, chronic high-dose NKB induces an increase in blood pressure through both central (indirect) and peripheral (direct) pathways.
Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Neurocinina B/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Técnicas In Vitro , Artérias Mesentéricas/fisiologia , Neurocinina B/administração & dosagem , Ratos , Ratos Long-Evans , Vasoconstrição/efeitos dos fármacosRESUMO
OBJECTIVES: Falls and fear of falling are a major health problem. We sought to determine the effectiveness of an educational intervention in reducing fear of falling and preventing recurrent falls in community-dwelling patients after a fragility fracture. METHODS: One hundred two community-dwelling patients aged 50 years or older who fell and sustained a wrist fracture and were treated at Emergency Departments in Edmonton, Alberta, Canada (2001-2002) were allocated to either standardized educational leaflets and post-discharge telephone counseling regarding fall prevention strategies ("intervention") or attention-controls ("controls"). Main outcomes were fear of falling and recurrent falls 3 months after fracture. RESULTS: Mean age was 67 years and most patients were female (80%). The majority of falls (76%) leading to fracture occurred outdoors. Three months post-fracture, almost half of patients (48%) reported increased fear of falling and 11 of 102 (11%) reported falling again. The intervention did not reduce the fear of falling (43% had increased fear vs. 53% of controls, adjusted P value=0.55) or decrease recurrent falls (17% fell vs. 5% of controls, adjusted P value=0.059) within 3 months of fracture. CONCLUSIONS: An educational intervention undertaken in the Emergency Department was no more effective than usual care in reducing fear of falling or recurrent falls in community-dwelling patients. Future strategies must address a number of dimensions beyond simple education.
Assuntos
Acidentes por Quedas/prevenção & controle , Medo/psicologia , Fraturas Ósseas/etiologia , Idoso Fragilizado/psicologia , Educação em Saúde , Traumatismos do Punho/etiologia , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Alberta/epidemiologia , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/prevenção & controle , Fraturas Ósseas/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Desenvolvimento de Programas , Recidiva , Traumatismos do Punho/epidemiologia , Traumatismos do Punho/prevenção & controle , Traumatismos do Punho/psicologiaRESUMO
PL74, a novel member of the TGFbeta superfamily that has highest expression in placenta, is a multifunctional peptide that can induce differentiation, inhibit inflammatory stimulation of TNFalpha, and execute apoptosis after p53 overexpression and cytotoxic injury. To study its expression and function in placenta and preeclampsia, we first determined mRNA expression in nine normal and 10 preeclamptic placentas. PL74 mRNA was overexpressed by 57.3% in preeclampsia. Transfection of PL74 into term cytotrophoblasts resulted in increased apoptosis by terminal uridine deoxynucleotidyl nick end labeling labeling (control, 2.8 +/- 0.5%; PL74, 19.1 +/- 0.2%; P < 0.005). Addition of PL74 protein to HTR8/SVneo extravillous cytotrophoblast cells showed a dose-response (0-100 ng/ml) inhibition of [3H]thymidine uptake and increase in apoptosis shown by terminal uridine deoxynucleotidyl nick end labeling and histone-associated DNA fragment ELISA (control, 0.11 +/- 0.01 absorbance units; PL74, 0.21 +/- 0.01; P < 0.01). PL74 did not alter cytotrophoblast invasion using a Matrigel in vitro invasion assay. Cytokine regulation of PL74 mRNA expression in term cytotrophoblasts showed that epidermal growth factor and IFNgamma increased PL74 expression, but TGFbeta and TNFalpha had no effect. Transfection of antisense PL74 into term cytotrophoblast cells resulted in an inhibition of spontaneous differentiation at 2 and 24 h of culture (control vector, 30.8 +/- 3.1% and 26.4 +/- 1.2%; antisense PL74, 17.6 +/- 1.8%and 12.6 +/- 1.4% syncytial units, at 2 and 24 h respectively; P < 0.01). We conclude that PL74 is overexpressed in preeclampsia and may thus promote apoptosis of cytotrophoblasts at the expense of differentiation. PL74 secretion is induced by IFNgamma and may play a role in abnormal placental responses in preeclampsia.
Assuntos
Apoptose , Pré-Eclâmpsia/metabolismo , Fator de Crescimento Transformador beta/genética , Trofoblastos/patologia , Biópsia , Diferenciação Celular , Células Cultivadas , Feminino , Humanos , Interferon gama/farmacologia , Placenta/metabolismo , Placenta/patologia , Gravidez , RNA Mensageiro/análise , Fator de Crescimento Transformador beta/fisiologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND: Despite the high risk for future fractures and the availability of effective treatments, fewer than 10% to 20% of patients who sustain a fragility fracture are tested or treated for osteoporosis. OBJECTIVES: To improve rates of testing and treatment for osteoporosis in patients with wrist fractures who are seen in the emergency department. DESIGN: Nonrandomized, controlled trial with blinded ascertainment of outcomes. SETTING: Emergency departments in Edmonton, Alberta, Canada. PATIENTS: Persons 50 years of age or older who were treated for a wrist fracture and their physicians. Patients admitted to the hospital or treated for osteoporosis were excluded. Overall, 572 consecutive patients with fractures were screened, and 102 patients (55 intervention, 47 control) and 101 physicians were studied. MEASUREMENTS: The primary end point was the prescription of osteoporosis treatment 6 months after fracture. Secondary end points included rates of testing for bone mineral density and patients' knowledge, satisfaction, and quality of life. INTERVENTION: Faxed physician reminders that contained osteoporosis treatment guidelines endorsed by local opinion leaders and patient education. Control patients received usual care and information about falls and home safety. RESULTS: The median patient age was 66 years. Most patients were female (78%) and white (79%); 70% of patients reported a previous fracture, and 22% had a fall with injury in the previous year. The intervention increased the rates of testing for bone mineral density to 62% (vs. 17% for controls; adjusted relative increase, 3.6 [P < 0.001]) and the rates of osteoporosis treatment to 40% (vs. 10% for controls; adjusted relative increase, 3.8 [P = 0.002]) within 6 months of fracture. Intervention patients were more likely to report a diagnosis of osteoporosis, but other patient-reported outcomes did not differ significantly between groups. LIMITATIONS: This was a small, nonrandomized, controlled study with process-based outcomes. CONCLUSIONS: In a multifaceted intervention directed at patients and their physicians, the rates of testing and treatment for osteoporosis after emergency department care for a fragility fracture were more than 3 times those of controls.
Assuntos
Fraturas Ósseas/etiologia , Osteoporose/diagnóstico , Traumatismos do Punho/etiologia , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Densidade Óssea , Canadá , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto , Satisfação do Paciente , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Qualidade de Vida , Sistemas de AlertaRESUMO
Placental neurokinin B (NKB) was recently identified as the causative agent in preeclampsia, a condition characterized by increased maternal and feto-placental vascular resistance. We hypothesized that NKB should constrict placental resistance vessels. Placentas were obtained from normotensive pregnancies. Immediately after delivery, stem villous arteries (300 microm diameter, 1.2 mm long) were dissected from macroscopically normal tissue in cold HEPES-physiological salt solution (PSS), mounted on a wire myograph system, and bathed in HEPES-PSS at 37 degrees C. After determination of the passive-tension internal circumference characteristics, the arteries were set to 90% of the internal circumference they would have under a normal physiological transmural pressure. Cumulative concentration-response curves were constructed for NKB (1 x 10(-12) to 1 x 10(-5) mol/l). Since there was no constrictive response to NKB, cumulative constrictive concentration-response curves were constructed to the thromboxane A(2) mimetic U46619 (1 x 10(-9) to 1 x 10(-5) mol/l). The vessels were then pre-constricted to 80% of maximal response and exposed to cumulative concentrations of NKB (1 x 10(-12) to 1 x 10(-6) mol/l). NKB caused a concentration-dependent relaxation (Maximal response NKB, 51+/-5%, n=5; time control, 12+/-6%, n=4; P<0.05). Removal of the endothelium did not alter the vasodilatory response to NKB. We conclude that, contrary to our hypothesis, NKB causes an endothelium-independent relaxation of the placental resistance vessels. We propose that NKB plays a role in the maintenance of high placental blood flow in normal pregnancy.