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1.
Artigo em Inglês | MEDLINE | ID: mdl-28271574

RESUMO

Monitoring screening mammography effects in small areas is often limited by small numbers of deaths and delayed effects. We developed a risk score for breast cancer death to circumvent these limitations. Screening, if effective, would increase post-diagnostic survivals through lead-time and related effects, as well as mortality reductions. Linked cancer and BreastScreen data at four hospitals (n = 2,039) were used to investigate whether screened cases had higher recorded survivals in 13 small areas, using breast cancer deaths as the outcome (M1), and a risk of death score derived from TNM stage, grade, histology type, hormone receptor status, and related variables (M2). M1 indicated lower risk of death in screened cases in 12 of the 13 areas, achieving statistical significance (p < .05) in 5. M2 indicated lower risk scores in screened cases in all 13 areas, achieving statistical significance in 12. For cases recently screened at diagnosis (<6 months), statistically significant reductions applied in 8 areas (M1) and all 13 areas (M2). Screening effects are more detectable in small areas using these risk scores than death itself as the outcome variable. An added advantage is the application of risk scores for providing a marker of screening effect soon after diagnosis.


Assuntos
Neoplasias da Mama/prevenção & controle , Detecção Precoce de Câncer/estatística & dados numéricos , Distribuição por Idade , Idoso , Neoplasias da Mama/mortalidade , Feminino , Humanos , Mamografia/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Análise de Pequenas Áreas , Fatores Socioeconômicos , Austrália do Sul/epidemiologia
2.
Phys Chem Chem Phys ; 18(34): 23462-8, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27507226

RESUMO

The development of technology to harvest the uranium dissolved in seawater would enable access to vast quantities of this critical metal for nuclear power generation. Amidoxime polymers are the most promising platforms for achieving this separation, yet the design of advanced adsorbents is hindered by uncertainty regarding the uranium binding mode. In this work we use XAFS to investigate the uranium coordination environment in an amidoxime-phosphonic acid copolymer adsorbent. In contrast to the binding mode predicted computationally and from small molecule studies, a cooperative chelating model is favoured, attributable to emergent behavior resulting from inclusion of amidoxime in the polymer. Samples exposed to seawater also display a feature consistent with a µ(2)-oxo-bridged transition metal, suggesting the formation of an in situ specific binding site. These findings challenge long held assumptions and provide new opportunities for the design of advanced adsorbent materials.

3.
Curr Sports Med Rep ; 14(1): 34-40, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25574880

RESUMO

Although sports-related injuries to the thoracic spine are relatively uncommon, they are among the most feared due to the potential for catastrophic neurologic injury. The increased biomechanical support of the thoracic spine makes injuries in this region particularly rare compared with the cervical and lumbar spine. As a result, thoracic spine injuries can be missed easily, difficult to diagnose, and problematic to treat. Recognition of mechanism and awareness of injury patterns help physicians determine a diagnosis and create an index of suspicion for unstable thoracic spine injuries. Aggressive full-contact sports receive the most attention for spinal injury; however several sports with repetitive loading of the spine can cause severe injuries, including rowing, gymnastics, and golf. The goal of this article was to provide an overview of the unique anatomic and biomechanical features of the thoracic spine and to discuss some of the more common thoracic injuries that can affect athletes.


Assuntos
Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/terapia , Traumatismos da Medula Espinal/epidemiologia , Traumatismos da Medula Espinal/terapia , Vértebras Torácicas/lesões , Traumatismos em Atletas/diagnóstico , Ginástica/lesões , Humanos , Traumatismos da Medula Espinal/diagnóstico
4.
Indian Heart J ; 75(1): 25-30, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36567065

RESUMO

AIM: The aim of this study was to assess the safety and efficacy profile of a newer generation biodegradable DES, the Yukon Choice PC Elite with a temperature controlling mechanism, in patients with acute coronary syndrome (ACS). METHODS: This prospective multi-center study (PIONEER Registry) was conducted in an Indian ACS population, therefore providing data in real world clinical practice. Patients with ACS underwent DES implantation in de novo native-vessel coronary lesions with the Yukon Choice PC Elite biodegradable polymer DES and were followed up for a year. RESULTS: A total 999 patients were evaluated. The majority of patients were male (79.2%). A total of 6.7% of the patients had a history of prior myocardial infarction (MI) and 2.7% of patients had a history of previous coronary artery bypass graft. The clinical presentations of the patients included: unstable angina pectoris (UA) (46.4%), ST-segment elevation MI (STEMI) (38.1%), and Non-ST-segment elevation MI (NSTEMI) (15.4%). Implantation of the device was successful in 99.9% of cases. The median stent length and stent size were 21.0 mm (Range: 8.0-40.0 mm) and 2.8 mm (Range 2.0-4.0 mm), respectively. Through to one-year clinical follow-up after percutaneous coronary intervention, all-cause death occurred in 4 of 999 patients (Crude Percentage: 0.4%). Cardiac death, MI, TLR, and stent thrombosis were occurred in 1 (0.1%), 8 (0.8%), 12 (1.2%) and 1 (0.1%) patients, respectively. CONCLUSION: The results of this post marketing surveillance registry suggest favorable safety and efficacy outcomes associated with the Yukon Choice PC Elite biodegradable DES in a real world Indian ACS population.


Assuntos
Síndrome Coronariana Aguda , Stents Farmacológicos , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Masculino , Feminino , Síndrome Coronariana Aguda/cirurgia , Estudos Prospectivos , Yukon , Resultado do Tratamento , Stents , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea/métodos , Sistema de Registros
5.
Br J Cancer ; 106(6): 1045-52, 2012 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-22415293

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SLNB) is less invasive than axillary lymph node dissection (ALND) for staging early breast cancer, and has a lower risk of arm lymphoedema and similar rates of locoregional recurrence up to 8 years. This study estimates the longer-term effectiveness and cost-effectiveness of SLNB. METHODS: A Markov decision model was developed to estimate the incremental quality-adjusted life years (QALYs) and costs of an SLNB-based staging and management strategy compared with ALND over 20 years' follow-up. The probability and quality-of-life weighting (utility) of outcomes were estimated from published data and population statistics. Costs were estimated from the perspective of the Australian health care system. The model was used to identify key factors affecting treatment decisions. RESULTS: The SLNB was more effective and less costly than the ALND over 20 years, with 8 QALYs gained and $883,000 saved per 1000 patients. The SLNB was less effective when: SLNB false negative (FN) rate >13%; 5-year incidence of axillary recurrence after an SLNB FN>19%; risk of an SLNB-positive result >48%; lymphoedema prevalence after ALND <14%; or lymphoedema utility decrement <0.012. CONCLUSION: The long-term advantage of SLNB over ALND was modest and sensitive to variations in key assumptions, indicating a need for reliable information on lymphoedema incidence and disutility following SLNB. In addition to awaiting longer-term trial data, risk models to better identify patients at high risk of axillary metastasis will be valuable to inform decision-making.


Assuntos
Neoplasias da Mama/patologia , Técnicas de Apoio para a Decisão , Excisão de Linfonodo/economia , Estadiamento de Neoplasias/métodos , Biópsia de Linfonodo Sentinela/economia , Axila , Neoplasias da Mama/diagnóstico , Análise Custo-Benefício , Feminino , Humanos , Metástase Linfática , Cadeias de Markov , Ensaios Clínicos Controlados Aleatórios como Assunto , Sensibilidade e Especificidade
6.
Eur J Pediatr ; 171(3): 601-2, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22159956

RESUMO

On routine neonatal examination, a newborn term male was noted to have unilateral enlargement of the right lower limb, loose thickened red skin over the palm and widening of all the fingers on the right hand. His body was pinker and warmer on the right side compared with the left and he had a right undescended testicle and hypoplastic scrotum. Radiological examination of the lower limbs demonstrated the enlargement of the soft tissue of the right lower limb compared to the left (Fig. 1). Therefore, the diagnosis was unclear from this constellation of findings and an ophthalmic assessment was requested.


Assuntos
Gigantismo/etiologia , Doenças Retinianas/etiologia , Esclerose Tuberosa/diagnóstico , Gigantismo/diagnóstico , Humanos , Recém-Nascido , Masculino , Doenças Retinianas/diagnóstico , Esclerose Tuberosa/complicações
7.
J Laryngol Otol ; 136(11): 1087-1095, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35300741

RESUMO

OBJECTIVE: Surgery is the recommended treatment for resectable T4a laryngeal and hypopharyngeal carcinoma. Non-surgical treatment is an option in a select few patients. METHOD: This retrospective study was undertaken to assess the treatment outcomes in patients with resectable T4a carcinoma of the larynx and hypopharynx who received either surgical or non-surgical treatment at our institute and to assess factors influencing these outcomes. RESULTS: A total of 120 patients were included in the study. They were divided into groups A, B and C based on the presence of extralaryngeal spread through laryngeal membrane, cartilage or both. The overall survival was better among patients who received surgery than those who received non-surgical treatment in the three groups. The factor influencing overall survival was the treatment given in the form of surgical versus non-surgical treatment. CONCLUSION: Surgery is the preferred treatment for T4a laryngeal and hypopharyngeal carcinoma, even in patients with extralaryngeal spread without cartilage erosion.


Assuntos
Carcinoma , Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Humanos , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Hipofaríngeas/terapia , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/terapia , Estudos Retrospectivos , Resultado do Tratamento , Carcinoma/cirurgia , Carcinoma/terapia
8.
Diabetologia ; 54(1): 19-24, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20835860

RESUMO

The International Insulin Foundation (IIF) has developed and validated a needs-assessment instrument called the Rapid Assessment Protocol for Insulin Access (RAPIA) which has been used in seven countries in four continents to analyse the constraints to delivering effective continuing care for people with diabetes. One major contributor to the difficulties in availability of insulin is a failure to use the least costly sources and types of insulin and other effective drugs for diabetes. The purchase of insulins can consume as much as 10% of government expenditure on drugs, this being highly sensitive to the selection of newer analogue insulins as first-choice options, which cost between three and 13 times more than biosynthetic human insulin. Insulin cartridges for use with injection pens further add to costs. Similar considerations apply to most of the newer treatments for people with type 2 diabetes, which may cost up to 40 times more than metformin and sulfonylureas, still considered first-line drugs by European and US guidelines. Both biosynthetic human insulin and the first-line oral hypoglycaemic drugs are available from generic manufacturers. With the present price differentials, there is thus a growing need for countries involved in tendering for sourcing insulin to be provided with the guarantees of Good Manufacturing Practice, quality and bioequivalence, which would come from a WHO Pre-Qualification Scheme as currently exists for a variety of drugs for chronic diseases, both communicable and non-communicable. The IIF has developed a position statement on the provision and choice of diabetes treatments in resource-limited settings which should be applicable wherever consideration of resources is a component of therapeutic decision making.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/economia , Insulina/economia , Animais , Análise Custo-Benefício , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico
9.
Diabetologia ; 54(1): 51-7, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20890591

RESUMO

AIMS/HYPOTHESIS: Surveys in northern Ethiopia have demonstrated that apparent type 1 diabetes occurs more frequently than elsewhere in Africa and, indeed, in other parts of the world. We therefore investigated in detail a cohort of diabetic patients from this region to clarify the nature of this type of diabetes. METHODS: All patients attending the diabetic clinic at Mekelle Hospital in the Tigray region of northern Ethiopia were investigated over a 6 week period. Clinical, demographic and anthropometric data were collected, as well as measurements of HbA(1c), fasting lipid profile, fasting serum C-peptide and serum markers of beta cell autoimmunity, i.e. islet antigen-2 and GAD antibodies (GADA). RESULTS: Of 105 patients seen, 69 (66%) were on insulin treatment and had been from or close to diagnosis. Their median age and diabetes duration were 30 and 5 years, respectively, with a male excess of 2:1. Median BMI was 20.6 kg/m². Despite these clinical characteristics suggestive of type 1 diabetes, only 42 of 69 (61%) patients were C-peptide-negative and 35% GADA-positive. Overall, 38 (36%) of the total group (n = 105) had immunological or C-peptide characteristics inconsistent with typical type 1 or type 2 diabetes. The clinical characteristics, local prevalence of undernutrition, and GADA and C-peptide heterogeneity suggest a malnutrition-related form of diabetes. CONCLUSIONS/INTERPRETATION: Not all patients in northern Ethiopia with apparent type 1 diabetes appear to have the form of disease seen in Europids; their disease may, in fact, be related to malnutrition.


Assuntos
Peptídeo C/sangue , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 2/imunologia , Desnutrição/sangue , Desnutrição/imunologia , Adulto , Autoanticorpos/sangue , Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Etiópia , Feminino , Glutamato Descarboxilase/imunologia , Humanos , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade
10.
Diabetologia ; 54(12): 3062-70, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21909837

RESUMO

AIMS/HYPOTHESIS: Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptor (KIR) genes and their HLA class I ligands. Alterations in NK cell activity have been associated with type 1 diabetes. The aim of this study was to determine whether KIR-HLA class I gene frequency: (1) is altered in a current population with type 1 diabetes compared with healthy controls; and (2) has changed over the half century in which the incidence of type 1 diabetes has increased rapidly. METHODS: KIR-HLA class I gene frequencies were compared in 551 individuals diagnosed with type 1 diabetes ≤ 15 years of age (394 in a current cohort and 157 from the historical 'Golden Years' cohort) and 168 healthy controls. The overall balance of activation and inhibition was analysed using KIR-HLA genotype models. RESULTS: Children with type 1 diabetes who were positive for KIR2DS2/KIR2DL2 and KIR2DL3 were more often homozygous for HLA-C group 1 and this effect was strongest in children diagnosed with diabetes before the age of 5 years (p = 0.003, corrected p [p (corr)] = 0.012) and (p = 0.001, p (corr) = 0.004), respectively. Children with type 1 diabetes have fewer inhibitory KIRs with their corresponding ligands compared with healthy controls (p = 1.9 × 10(-4)). This pattern of NK activation has not changed significantly in individuals with type 1 diabetes over the last half century. CONCLUSIONS/INTERPRETATION: Activating combinations of KIR-HLA genes are more frequent in young children with type 1 diabetes diagnosed in the first 5 years of life, suggesting that NK cell responses may be altered in this group.


Assuntos
Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Antígenos HLA-C/genética , Antígenos HLA-C/imunologia , Receptores de Células Matadoras Naturais/genética , Receptores de Células Matadoras Naturais/imunologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Frequência do Gene/genética , Frequência do Gene/imunologia , Homozigoto , Humanos , Lactente , Células Matadoras Naturais/imunologia , Masculino
11.
Curr Opin Cell Biol ; 11(4): 483-8, 1999 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10449328

RESUMO

Is there mitogenic signaling during endocytosis or is receptor internalization mainly an attenuator of signals? Recent data indicate that the answer appears to be yes to both questions. Signal transduction occurs physiologically from the cell surface and endocytosis downregulates signaling by removing receptors from the plasma membrane. In cancer, the involvement of endocytic/sorting proteins points to dysregulation of apparently unrelated pathways, which might account for an important causative role in neoplasia.


Assuntos
Endocitose/fisiologia , Mitógenos/metabolismo , Transdução de Sinais , Animais , Transporte Biológico , Membrana Celular , Clatrina/metabolismo , Invaginações Revestidas da Membrana Celular/metabolismo , Humanos , Leucemia Mieloide Aguda/metabolismo
12.
Nat Cell Biol ; 1(5): 253-9, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10559936

RESUMO

Extracellular signals regulate actin dynamics through small GTPases of the Rho/Rac/Cdc42 (p21) family. Here we show that p21-activated kinase (Pak1) phosphorylates LIM-kinase at threonine residue 508 within LIM-kinase's activation loop, and increases LIM-kinase-mediated phosphorylation of the actin-regulatory protein cofilin tenfold in vitro. In vivo, activated Rac or Cdc42 increases association of Pak1 with LIM-kinase; this association requires structural determinants in both the amino-terminal regulatory and the carboxy-terminal catalytic domains of Pak1. A catalytically inactive LIM-kinase interferes with Rac-, Cdc42- and Pak1-dependent cytoskeletal changes. A Pak1-specific inhibitor, corresponding to the Pak1 autoinhibitory domain, blocks LIM-kinase-induced cytoskeletal changes. Activated GTPases can thus regulate actin depolymerization through Pak1 and LIM-kinase.


Assuntos
Actinas/fisiologia , Citoesqueleto/fisiologia , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteína cdc42 de Ligação ao GTP/metabolismo , Proteínas rac de Ligação ao GTP/metabolismo , Animais , Células COS , Linhagem Celular , Membrana Celular/fisiologia , Membrana Celular/ultraestrutura , Ativação Enzimática , Humanos , Cinética , Quinases Lim , Mutagênese Sítio-Dirigida , Fosforilação , Fosfotreonina/metabolismo , Proteínas Recombinantes/metabolismo , Deleção de Sequência , Transdução de Sinais , Transfecção , Dedos de Zinco , Quinases Ativadas por p21
13.
Diabet Med ; 28(3): 373-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21204963

RESUMO

AIM: To compare the effects of a dedicated cardiovascular risk factor clinic run by a nurse consultant with routine diabetes clinic attendance in achieving glycaemic and cardiovascular risk targets in patients with Type 1 diabetes. METHODS: Eighty-one patients (45 male, mean age 34.6 years, mean duration of diabetes 15 years) with an HbA(1c) ≥ 8% (64 mmol/mol) and at least one other risk factor for the development of cardiovascular disease were randomized to receive either routine care or intensive nurse-led cardiovascular risk factor intervention. HbA(1c) , non-fasting lipid profile, blood pressure, weight, BMI and insulin dose were recorded at baseline, 6, 12 and 24 months. RESULTS: At baseline there were no differences between the groups. At 12 months, there were significant improvements in the nurse-led cardiovascular risk factor group: HbA(1c) [10.1% (87 mmol/mol) vs. 9.3% (78 mmol/mol), P < 0.001], total cholesterol (5.8 vs. 4.3 mmol/l, P < 0.001), systolic blood pressure (127 vs. 115 mmHg, P < 0.001) and diastolic blood pressure (71 vs. 65 mmHg, P < 0.05). Improvements were maintained in all variables at 24 months except diastolic blood pressure. In the routine group, only total cholesterol improved significantly (5.8 vs. 5.2 mmol/l, P < 0.01) after 12 months and this was maintained at 24 months. CONCLUSION: A nurse consultant cardiovascular risk factor clinic has a beneficial effect on cardiovascular risk targets in Type 1 diabetes, probably attributable to the increased use of lipid-lowering and anti-hypertensive agents and this was maintained at 24 months. Glycaemic control also improved.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 1/complicações , Angiopatias Diabéticas/prevenção & controle , Hipoglicemiantes/administração & dosagem , Adulto , Assistência Ambulatorial , Glicemia/análise , Doenças Cardiovasculares/enfermagem , Diabetes Mellitus Tipo 1/enfermagem , Angiopatias Diabéticas/enfermagem , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Comportamento de Redução do Risco
14.
Extremophiles ; 15(1): 59-65, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21125411

RESUMO

Cyclization in glycerol dibiphytanyl glycerol tetraethers (GDGTs) results in internal cyclopentane moieties which are believed to confer thermal stability to crenarchaeal membranes. While the average number of rings per GDGT lipid (ring index) is positively correlated with temperature in many temperate environments, poor correlations are often observed in geothermal environments, suggesting that additional parameters may influence GDGT core lipid composition in these systems. However, the physical and chemical parameters likely to influence GDGT cyclization which are often difficult to decouple in geothermal systems, making it challenging to assess their influence on lipid composition. In the present study, the influence of temperature (range 65-81°C), pH (range 3.0-5.0), and ionic strength (range 10.1-55.7 mM) on GDGT core lipid composition was examined in the hyperthermoacidophile Acidilobus sulfurireducens, a crenarchaeon originally isolated from a geothermal spring in Yellowstone National Park, Wyoming. When cultivated under defined laboratory conditions, the composition of individual and total GDGTs varied significantly with temperature and to a lesser extent with the pH of the growth medium. Ionic strength over the range of values tested did not influence GDGT composition. The GDGT core lipid ring index was positively correlated with temperature and negatively correlated with pH, suggesting that A. sulfurireducens responds to increasing temperature and acidity by increasing the number of cyclopentyl rings in GDGT core membrane lipids.


Assuntos
Crenarchaeota/metabolismo , Éteres de Glicerila/metabolismo , Lipídeos de Membrana/metabolismo , Crenarchaeota/crescimento & desenvolvimento , Temperatura Alta , Concentração de Íons de Hidrogênio
15.
Diabet Med ; 27(8): 933-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20653752

RESUMO

AIMS: The primary aim was to assess long-term blood pressure in 110 patients with Type 2 diabetes who had achieved optimal blood pressure control during attendance at a protocol-based nurse-led hypertension intensive intervention clinic 7 years previously. The secondary aim was to assess modifiable cardiovascular risk factor status. METHODS: One hundred and ten patients who attended the clinic during 2000-2002 were selected to reattend to have their blood pressure measured to the same standard as it was during the intensive intervention clinic, by the same specialist nurse. Treatment details were recorded. RESULTS: Of the 110 patients, 36 (33%) had died; 69 (63%) of the remaining 74 patients were eligible to be contacted by letter; and 35 (51%) agreed to reattend. Age was 70 +/- 9 years; 21 (60%) were male; and the duration of diabetes was 17 +/- 7 years. Compared with 7 years previously, there was no difference in blood pressure control (systolic 130 +/- 17 vs. 131 +/- 16 mmHg, P = 0.62; diastolic 68 +/- 9 vs. 65 +/- 9 mmHg, P = 0.11). The number of patients with blood pressure <130/80 mmHg remained the same: 17 (49%) vs. 17 (49%; P > 0.99). During the 7 year period, 14 (40%) vs. 20 (57%) had macrovascular disease (P = 0.23), and 14 (40%) vs. 19 (54%) microvascular disease (P = 0.33). Thirteen (37%) vs. 18 (51%) were taking three or more antihypertensive drugs (P = 0.33), and 26 (74%) vs. 28 (80%) angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (P = 0.77). CONCLUSIONS: Optimal blood pressure control was sustained with no significant changes to antihypertensive medication, demonstrating the effectiveness of a protocol-based nurse-led clinic in achieving strict BP control.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Angiopatias Diabéticas/fisiopatologia , Hipertensão/fisiopatologia , Idoso , Instituições de Assistência Ambulatorial/normas , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/enfermagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/enfermagem , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/enfermagem , Feminino , Seguimentos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/enfermagem , Masculino
16.
Curr Oncol ; 27(6): e552-e559, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33380870

RESUMO

Background: Tyrosine kinase inhibitors (tkis) have dramatically improved the survival of patients with ALK-rearranged (ALK+) non-small-cell lung cancer (nsclc). Clinical trial data can generally compare drugs in a pair-wise fashion. Real-world collection of health utility data, symptoms, and toxicities allows for the direct comparison between multiple tki therapies in the population with ALK+ nsclc. Methods: In a prospective cohort study, outpatients with ALK+ recruited between 2014 and 2018, treated with a variety of tkis, were assessed every 3 months for clinico-demographic, patient-reported symptom and toxicity data and EQ-5D-derived health utility scores (hus). Results: In 499 longitudinal encounters of 76 patients with ALK+ nsclc, each tki had stable longitudinal hus when disease was controlled, even after months to years: the mean overall hus for each tki ranged from 0.805 to 0.858, and longitudinally from 0.774 to 0.912, with higher values associated with second- or third-generation tkis of alectinib, brigatinib, and lorlatinib. Disease progression was associated with a mean hus decrease of 0.065 (95% confidence interval: 0.02 to 0.11). Health utility scores were inversely correlated to multiple symptoms or toxicities: rho values ranged from -0.094 to -0.557. Fewer symptoms and toxicities were associated with the second- and third-generation tkis compared with crizotinib. In multivariable analysis, only stable disease state and baseline Eastern Cooperative Oncology Group performance status were associated with improved hus. Conclusions: There was no significant decrease in hus when patients with ALK+ disease were treated longitudinally with each tki, as long as patients were clinically stable. Alectinib, brigatinib, and lorlatinib had the best toxicity profiles and exhibited high mean hus longitudinally in the real-world setting.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Quinase do Linfoma Anaplásico/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos
17.
Diabetologia ; 52(1): 42-5, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18972096

RESUMO

AIMS/HYPOTHESIS: Sudden nocturnal death in type 1 diabetes ('dead in bed' syndrome) is thought to be due to ECG QT prolongation with subsequent ventricular tachyarrhythmia in response to nocturnal hypoglycaemia. We investigated this theoretical mechanism using continuous ECG and continuous glucose monitoring in a group of patients with type 1 diabetes. METHODS: Twenty-five patients with type 1 diabetes (age 20-50 years) underwent two separate 24 h ECG and continuous glucose monitoring periods. Patients were fully ambulant and carried out normal daily activities. RESULTS: There were 13 episodes (26% of recordings) of nocturnal hypoglycaemia, eight of <2.2 mmol/l and five of 2.2-3.4 mmol/l. Corrected QT interval (QTc) was longer during nocturnal hypoglycaemia compared with normoglycaemic control periods (445 +/- 40 vs 415 +/- 23 ms; p = 0.037). Cardiac rate and rhythm disturbances (excluding sinus tachycardia) were seen in eight of the 13 nocturnal hypoglycaemia episodes (62%). These were sinus bradycardia (<40 beats/min; three episodes), ventricular ectopics (three episodes), atrial ectopics (one) and P wave abnormalities (one). CONCLUSIONS/INTERPRETATION: This study demonstrates QTc prolongation and cardiac rate/rhythm disturbances in response to episodes of nocturnal hypoglycaemia in ambulant patients with type 1 diabetes. This may support an arrhythmic basis for the 'dead in bed' syndrome.


Assuntos
Arritmias Cardíacas/fisiopatologia , Glicemia/análise , Ritmo Circadiano/fisiologia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Hipoglicemia/fisiopatologia , Sono/fisiologia , Adulto , Arritmias Cardíacas/epidemiologia , Bradicardia/epidemiologia , Eletrocardiografia , Frequência Cardíaca , Humanos , Síndrome do QT Longo/epidemiologia , Pessoa de Meia-Idade , Monitorização Ambulatorial , Monitorização Fisiológica/métodos , Taquicardia Atrial Ectópica/epidemiologia , Adulto Jovem
18.
Diabetologia ; 52(1): 8-16, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18846363

RESUMO

Diabetes mellitus is an important and increasing cause of morbidity and mortality in sub-Saharan Africa. Accurate epidemiological studies are often logistically and financially difficult, but processes of rural-urban migration and epidemiological transition are certainly increasing the prevalence of type 2 diabetes. Type 1 disease is relatively rare, although this may be related to high mortality. This diabetic subgroup appears to present at a later age (by about a decade) than in Western countries. Variant forms of diabetes are also described in the continent; notably 'atypical, ketosis-prone' diabetes, and malnutrition-related diabetes mellitus. These types sometimes make the distinction between type 1 and type 2 diabetes difficult. Interestingly, this is also a current experience in the developed world. As more detailed and reliable complication studies emerge, it is increasingly apparent that African diabetes is associated with a high complication burden, which is both difficult to treat and prevent. More optimistically, a number of intervention studies and twinning projects are showing real benefits in varying locations. Future improvements depend on practical and sustainable support, coupled with local acceptance of diabetes as a major threat to the future health and quality of life of sub-Saharan Africans.


Assuntos
Diabetes Mellitus/epidemiologia , Adulto , África Subsaariana/epidemiologia , Diabetes Mellitus/classificação , Diabetes Mellitus/etiologia , Diabetes Mellitus/mortalidade , Humanos , Incidência , Desnutrição/complicações , Prevalência , População Urbana/estatística & dados numéricos
19.
Environ Microbiol ; 11(4): 950-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19170726

RESUMO

Microbial mats are a visible and abundant life form inhabiting the extreme environments in Yellowstone National Park (YNP), WY, USA. Little is known of their role in food webs that exist in the Park's geothermal habitats. Eukaryotic green algae associated with a phototrophic green/purple Zygogonium microbial mat community that inhabits low-temperature regions of acidic (pH approximately 3.0) thermal springs were found to serve as a food source for stratiomyid (Diptera: Stratiomyidae) larvae. Mercury in spring source water was taken up and concentrated by the mat biomass. Monomethylmercury compounds (MeHg(+)), while undetectable or near the detection limit (0.025 ng l(-1)) in the source water of the springs, was present at concentrations of 4-7 ng g(-1) dry weight of mat biomass. Detection of MeHg(+) in tracheal tissue of larvae grazing the mat suggests that MeHg(+) enters this geothermal food web through the phototrophic microbial mat community. The concentration of MeHg(+) was two to five times higher in larval tissue than mat biomass indicating MeHg(+) biomagnification occurred between primary producer and primary consumer trophic levels. The Zygogonium mat community and stratiomyid larvae may also play a role in the transfer of MeHg(+) to species in the food web whose range extends beyond a particular geothermal feature of YNP.


Assuntos
Clorófitas/metabolismo , Cadeia Alimentar , Sedimentos Geológicos/microbiologia , Compostos de Metilmercúrio/metabolismo , Animais , Dípteros/fisiologia , Comportamento Alimentar , Traqueia/química , Água/análise , Wyoming
20.
Appl Environ Microbiol ; 75(13): 4289-96, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19429558

RESUMO

Carbon fixation at temperatures above 73 degrees C, the upper limit for photosynthesis, is carried out by chemosynthetic thermophiles. Yellowstone National Park (YNP), Wyoming possesses many thermal features that, while too hot for photosynthesis, presumably support chemosynthetic-based carbon fixation. To our knowledge, in situ rates of chemosynthetic reactions at these high temperatures in YNP or other high-temperature terrestrial geothermal springs have not yet been reported. A microbial community attached to precipitated elemental sulfur (S(o) floc) at the source of Dragon Spring (73 degrees C, pH 3.1) in Norris Geyser Basin, YNP, exhibited a maximum rate of CO(2) uptake of 21.3 +/- 11.9 microg of C 10(7) cells(-1) h(-1). When extrapolated over the estimated total quantity of S(o) floc at the spring's source, the S(o) floc-associated microbial community accounted for the uptake of 121 mg of C h(-1) at this site. On a per-cell basis, the rate was higher than that calculated for a photosynthetic mat microbial community dominated by Synechococcus spp. in alkaline springs at comparable temperatures. A portion of the carbon taken up as CO(2) by the S(o) floc-associated biomass was recovered in the cellular nucleic acid pool, demonstrating that uptake was coupled to fixation. The most abundant sequences in a 16S rRNA clone library of the S(o) floc-associated community were related to chemolithoautotrophic Hydrogenobaculum strains previously isolated from springs in the Norris Geyser Basin. These microorganisms likely contributed to the uptake and fixation of CO(2) in this geothermal habitat.


Assuntos
Bactérias/classificação , Bactérias/metabolismo , Dióxido de Carbono/metabolismo , Fontes Termais/microbiologia , Bactérias/genética , Bactérias/isolamento & purificação , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Dados de Sequência Molecular , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Wyoming
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