RESUMO
AIMS: To assess the effects of 'clinical' and 'intensification inertia' by evaluating the impact of different intensification interventions on the probability of HbA1c goal attainment using real-world data. METHODS: Electronic health records (Cleveland Clinic, 2005-2016) were used to identify 7389 people with Type 2 diabetes mellitus and HbA1c ≥53 mmol/mol (≥7.0%), despite a stable regimen of two oral antihyperglycaemic drugs for ≥6 months. The participants were stratified by index HbA1c and analysed over a 6-month period for pharmacological intensification, and then for 12 additional months for HbA1c goal attainment (<53 mmol/mol). RESULTS: The probability of HbA1c goal attainment (Kaplan-Meier analysis) in the group with index HbA1c 53-63 mmol/mol (7.0-7.9%) was highest with the addition of oral antidiabetic drugs [57.3% (95% CI 52.1, 62.0)] or glucagon-like peptide-1 receptor agonists [56.7% (95% CI 40.4, 68.6)], in the 64-74 mmol/mol (8.0-8.9%) group with the addition of oral antidiabetic drugs [31.9% (95% CI 25.1, 38.1)] or insulin [30.6% (95% CI 18.3, 41.0)], and in the ≥75 mmol/mol (≥9.0%) group with the addition of glucagon-like peptide-1 receptor agonists [53.0% (95% CI 31.8, 67.6)] or insulin [43.5% (95% CI 36.4, 49.8)]. CONCLUSIONS: Numerical, but not statistically significant, differences in HbA1c goal attainment probability by type of intensification were most marked in people with the highest index HbA1c [≥75 mmol/mol (≥9.0%)]; in this group, injectable therapy showed trends toward greater glycaemic control benefits. Additional research into the phenomenon of intensification inertia is warranted.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico/métodos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Planejamento de Assistência ao Paciente , Resultado do TratamentoRESUMO
STUDY QUESTION: Can a novel targeted next generation sequencing (tNGS) platform accurately detect whole chromosome aneuploidy in a trophectoderm biopsy and provide additional information to improve testing? SUMMARY ANSWER: Karyotypes obtained by tNGS were concordant with other validated platforms and single nucleotide polymorphism genotyping information obtained can be used for improved detection and quality control. WHAT IS KNOWN ALREADY: qPCR-based whole chromosome aneuploidy screening is highly accurate in comparison to other common methods and has been shown to improve IVF success in two randomized clinical trials. With aneuploidy screening becoming standard of care in many IVF centres, there is a need to develop platforms with high throughput, low cost capabilities. STUDY DESIGN SIZE, DURATION: Twelve well-characterized cell lines were obtained from a commercial cell line repository and 31 discarded human blastocysts were obtained from 17 IVF patients who underwent comprehensive chromosome screening (CCS). PARTICIPANTS/MATERIAL, SETTING, METHODS: All samples were processed using a unique amplification strategy which directly incorporated sequencing library adapters and barcodes. Sequencing was performed on an Ion Torrent Proton. A custom bioinformatics pipeline was used to determine the karyotype for each sample. The consistency of tNGS diagnoses with either conventional karyotyping of cell lines or quantitative real-time PCR based CCS of blastocyst biopsies was evaluated. MAIN RESULTS AND THE ROLE OF CHANCE: Overall consistency per sample of tNGS based CCS in 5-cell samples from a variety of cell lines was 99.2%. In the blinded analysis of rebiopsies of aneuploid blastocysts, an overall targeted tNGS CCS consistency of 98.7% was observed per sample. These data demonstrate the ability of tNGS based CCS to provide an accurate and high throughput evaluation of aneuploidy in the human blastocyst. LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: This study is limited to whole chromosome aneuploidy, as mosaicism and segmental aneuploidy have not been investigated. WIDER IMPLICATIONS OF THE FINDINGS: These data show an accurate, high throughput method, and with the greater depth of each amplicon sequenced in comparison to commercial kits, there is greater application available for single nucleotide polymorphism based analysis for quality control. STUDY FUNDING/COMPETING INTERESTS: This study was funded through intramural research funds provided by the Foundation for Embryonic Competence. There are no competing interests.
Assuntos
Blastocisto/citologia , Blastocisto/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Aneuploidia , Linhagem Celular , Biologia Computacional , Feminino , Humanos , GravidezRESUMO
AIMS: Sulfonylureas have been shown to increase mortality when used in combination with metformin. This may not be a class effect of sulfonylureas, but rather secondary to differences in properties inherent to the individual sulfonylureas (hypoglycaemic risk, sulfonylurea receptor selectivity and effects on myocardial ischemic preconditioning). The purpose of this study was to assess the risk of overall mortality in patients with Type 2 diabetes treated with different combinations of sulfonylureas and metformin. METHODS: A retrospective cohort study was conducted using an academic health center enterprise-wide electronic health record system to identify 7320 patients with Type 2 diabetes (3768 initiators of glyburide (glibenclamide) and metformin, 2277 initiators of glipizide and metformin and 1275 initiators of glimepiride and metformin), ≥ 18 years of age and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the electronic health record and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. RESULTS: No statistically significant difference in overall mortality risk was observed among the different combinations of sulfonylureas and metformin: glimepiride and metformin vs. glipizide and metformin (HR 1.03; 95% CI 0.89-1.20), glimepiride and metformin vs. glyburide (glibenclamide) and metformin (HR 1.08; 95% CI 0.90-1.30), or with glipizide and metformin vs. glyburide (glibenclamide) and metformin (HR 1.05; 95% CI 0.95-1.15). CONCLUSIONS: Our results did not identify an increased mortality risk among the different combinations of sulfonylureas and metformin, suggesting that overall mortality is not substantially influenced by the choice of sulfonylurea.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/mortalidade , Quimioterapia Combinada/métodos , Feminino , Glipizida/uso terapêutico , Glibureto/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
AIMS: It remains uncertain if differences in mortality risk exist among the sulfonylureas, especially in patients with documented coronary artery disease (CAD). The purpose of this study was to assess the overall mortality risk of the individual sulfonylureas versus metformin in a large cohort of patients with type 2 diabetes. METHODS: A retrospective cohort study was conducted using an academic health centre enterprise-wide electronic health record (EHR) system to identify 23 915 patients with type 2 diabetes who initiated monotherapy with metformin (N = 12774), glipizide (N = 4325), glyburide (N = 4279) or glimepiride (N = 2537), ≥ 18 years of age, with and without a history of CAD, and not on insulin or a non-insulin injectable at baseline. The patients were followed for mortality by documentation in the EHR and Social Security Death Index. Multivariable Cox models with propensity analysis were used to compare cohorts. RESULTS: An increase in overall mortality risk was observed in the entire cohort with glipizide (HR 1.64; 95% CI 1.39-1.94), glyburide (HR 1.59; 95% CI 1.35-1.88), and glimepiride (HR 1.68; 95% CI 1.37-2.06) versus metformin; however, in those patients with documented CAD, a statistically significant increase in overall mortality risk was only found with glipizide (HR 1.41; 95% CI 1.07-1.87) and glyburide (HR 1.38; 95% CI 1.04-1.83) versus metformin. CONCLUSIONS: Glipizide, glyburide and glimepiride are associated with an increased risk of overall mortality versus metformin. Our results suggest that if a sulfonylurea is required to obtain glycaemic control, glimepiride may be the preferred sulfonylurea in those with underlying CAD.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Adulto , Idoso , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Glipizida/uso terapêutico , Glibureto/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Compostos de Sulfonilureia/uso terapêutico , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Perfusion MR imaging measures of relative CBV can distinguish recurrent tumor from posttreatment radiation effects in high-grade gliomas. Currently, relative CBV measurement requires normalization based on user-defined reference tissues. A recently proposed method of relative CBV standardization eliminates the need for user input. This study compares the predictive performance of relative CBV standardization against relative CBV normalization for quantifying recurrent tumor burden in high-grade gliomas relative to posttreatment radiation effects. MATERIALS AND METHODS: We recruited 38 previously treated patients with high-grade gliomas (World Health Organization grades III or IV) undergoing surgical re-resection for new contrast-enhancing lesions concerning for recurrent tumor versus posttreatment radiation effects. We recovered 112 image-localized biopsies and quantified the percentage of histologic tumor content versus posttreatment radiation effects for each sample. We measured spatially matched normalized and standardized relative CBV metrics (mean, median) and fractional tumor burden for each biopsy. We compared relative CBV performance to predict tumor content, including the Pearson correlation (r), against histologic tumor content (0%-100%) and the receiver operating characteristic area under the curve for predicting high-versus-low tumor content using binary histologic cutoffs (≥50%; ≥80% tumor). RESULTS: Across relative CBV metrics, fractional tumor burden showed the highest correlations with tumor content (0%-100%) for normalized (r = 0.63, P < .001) and standardized (r = 0.66, P < .001) values. With binary cutoffs (ie, ≥50%; ≥80% tumor), predictive accuracies were similar for both standardized and normalized metrics and across relative CBV metrics. Median relative CBV achieved the highest area under the curve (normalized = 0.87, standardized = 0.86) for predicting ≥50% tumor, while fractional tumor burden achieved the highest area under the curve (normalized = 0.77, standardized = 0.80) for predicting ≥80% tumor. CONCLUSIONS: Standardization of relative CBV achieves similar performance compared with normalized relative CBV and offers an important step toward workflow optimization and consensus methodology.
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Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/normas , Imageamento por Ressonância Magnética/normas , Neuroimagem/métodos , Adulto , Idoso , Neoplasias Encefálicas/patologia , Feminino , Glioma/patologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/patologia , Carga TumoralRESUMO
BACKGROUND AND PURPOSE: MR imaging-based modeling of tumor cell density can substantially improve targeted treatment of glioblastoma. Unfortunately, interpatient variability limits the predictive ability of many modeling approaches. We present a transfer learning method that generates individualized patient models, grounded in the wealth of population data, while also detecting and adjusting for interpatient variabilities based on each patient's own histologic data. MATERIALS AND METHODS: We recruited patients with primary glioblastoma undergoing image-guided biopsies and preoperative imaging, including contrast-enhanced MR imaging, dynamic susceptibility contrast MR imaging, and diffusion tensor imaging. We calculated relative cerebral blood volume from DSC-MR imaging and mean diffusivity and fractional anisotropy from DTI. Following image coregistration, we assessed tumor cell density for each biopsy and identified corresponding localized MR imaging measurements. We then explored a range of univariate and multivariate predictive models of tumor cell density based on MR imaging measurements in a generalized one-model-fits-all approach. We then implemented both univariate and multivariate individualized transfer learning predictive models, which harness the available population-level data but allow individual variability in their predictions. Finally, we compared Pearson correlation coefficients and mean absolute error between the individualized transfer learning and generalized one-model-fits-all models. RESULTS: Tumor cell density significantly correlated with relative CBV (r = 0.33, P < .001), and T1-weighted postcontrast (r = 0.36, P < .001) on univariate analysis after correcting for multiple comparisons. With single-variable modeling (using relative CBV), transfer learning increased predictive performance (r = 0.53, mean absolute error = 15.19%) compared with one-model-fits-all (r = 0.27, mean absolute error = 17.79%). With multivariate modeling, transfer learning further improved performance (r = 0.88, mean absolute error = 5.66%) compared with one-model-fits-all (r = 0.39, mean absolute error = 16.55%). CONCLUSIONS: Transfer learning significantly improves predictive modeling performance for quantifying tumor cell density in glioblastoma.
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Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia , Aprendizado de Máquina , Neuroimagem/métodos , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
To determine whether endothelin (ET) has a role in maintaining circulatory support during hypotensive hemorrhage, we (1) examined cardiac and systemic hemodynamics after a 6-mL hemorrhage in the presence and absence of the ETA receptor blocker BQ-123, (2) examined cardiac and systemic hemodynamics during BQ-123 infusion in nonhemorrhaged rats, (3) measured changes in circulating immunoreactive endothelin (IR-ET) after a 6-mL hemorrhage, and (4) infused pathophysiological doses of ET-1 into rats anesthetized with thiobutabarbital. Twenty minutes after hemorrhage, cardiac output and mean arterial pressure had stabilized in part because of an increase in systemic vascular resistance from 0.86 +/- 0.04 (baseline) to 1.04 +/- 0.05 (20 minutes) mm Hg/mL per minute. The rise in systemic vascular resistance was temporally associated with a significant (24%) increase in circulating IR-ET from 29 +/- 2 to 36 +/- 3 pg/mL 20 minutes after hemorrhage. During BQ-123 infusion mean arterial pressure at 5, 10, and 20 minutes after hemorrhage was 9 +/- 2, 23 +/- 4, and 23 +/- 3 mm Hg lower than values obtained after hemorrhage alone (P < .05). Mean arterial pressure was unaffected by BQ-123 infusion at baseline and 30 minutes after hemorrhage. Systemic vascular resistance was not affected at baseline by BQ-123 infusion. However, systemic vascular resistance was significantly lower 5, 10, 20, and 30 minutes after hemorrhage during BQ-123 infusion compared with hemorrhage alone at each time point. Infusion of BQ-123 into nonhemorrhaged rats had no effect on mean arterial pressure, systemic vascular resistance, or cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Endotelinas/fisiologia , Choque Hemorrágico/fisiopatologia , Resistência Vascular , Animais , Pressão Sanguínea , Masculino , Peptídeos Cíclicos/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Reflex activation of the sympathetic nervous system may conceal direct vasodilatory actions of atrial natriuretic factor and mediate atrial natriuretic factor-induced increases in total peripheral resistance. We determined whether peripheral sympathectomy would enhance the hypotensive actions of atrial natriuretic factor and convert the increase in total peripheral resistance to peripheral vasodilation. Sympathectomized rats studied included 1) conscious rats treated with 6-hydroxydopamine alone (partially sympathectomized) and 2) conscious anephric rats sympathectomized with adrenal demedullation and 6-hydroxydopamine (totally sympathectomized), with vascular tone returned to levels of sham-operated (control) rats with norepinephrine infusion. Sympathectomized rats and appropriate control rats received rat atrial natriuretic factor infusion (0.5 microgram/kg/min) or vehicle for 1 hour. Atrial natriuretic factor infusion lowered mean arterial pressure and increased hematocrit in control rats but not in partially sympathectomized rats. Changes in cardiac output and total peripheral resistance were not significantly different between control and partially sympathectomized rats. In totally sympathectomized rats, atrial natriuretic factor lowered mean arterial pressure more than in control rats; changes in cardiac output were nearly identical in both groups, but there were no changes in total peripheral resistance from control levels in the totally sympathectomized group. Changes in plasma volume and central venous pressure were similar in totally sympathectomized rats and control rats. These findings suggest that reflex sympathetic activity largely mediated atrial natriuretic factor-induced increases in total peripheral resistance but failed to reveal an atrial natriuretic factor-mediated sustained vasodilation in the absence of sympathetic reflexes. Furthermore, atrial natriuretic factor decreased cardiac output, central venous pressure, and plasma volume independent of the sympathetic nervous system.
Assuntos
Fator Natriurético Atrial/farmacologia , Simpatectomia Química , Vasodilatação/efeitos dos fármacos , Medula Suprarrenal/fisiologia , Animais , Frequência Cardíaca/efeitos dos fármacos , Hematócrito , Hidroxidopaminas/farmacologia , Masculino , Oxidopamina , Ratos , Ratos Endogâmicos , Resistência Vascular/efeitos dos fármacosRESUMO
The effect of hypothyroidism on circulating levels of atrial natriuretic peptide (ANP) was studied in 11 hypothyroid patients (aged 11-65 yr; mean, 31 yr) and 13 normal subjects (aged 28-39 yr; mean, 32 yr). Plasma ANP was 32 +/- 9 (+/- SD) pg/ml in normal subjects and 20 +/- 5 pg/ml in the hypothyroid patients (P less than 0.005). In 7 hypothyroid patients, plasma ANP levels were measured after 10-14 weeks of L-T4 therapy. ANP increased from 22 +/- 5 to 46 +/- 18 pg/ml (P less than 0.02), along with an increase in mean serum T4 from 0.6 +/- 0.5 to 8.1 +/- 2.5 micrograms/dl (P less than 0.001). Thus, hypothyroidism is characterized by decreased circulating levels of ANP which are reversed by L-T4 therapy.
Assuntos
Fator Natriurético Atrial/sangue , Hipotireoidismo/sangue , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Hipotireoidismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Tireotropina/sangue , Tiroxina/uso terapêuticoRESUMO
The relationship between plasma atrial natriuretic peptide (ANP) and mineralocorticoid escape was examined in six normal men (age, 20-32 yr) treated with 0.4 mg/day fludrocortisone acetate for 9-14 days. Urinary sodium excretion decreased from 162 +/- 15 (SEM) meq/24 h before to 97 +/- 10 meq/24 h during fludrocortisone acetate administration (P less than 0.05). Despite continued fludrocortisone acetate administration, sodium excretion subsequently returned to baseline (escape). Plasma ANP increased from 33 +/- 6 pg/ml (control) to 55 +/- 14 pg/ml on the first day of escape (P less than 0.05). Escape was associated with a decrease in PRA from 0.90 +/- 0.22 (control) to 0.26 +/- 0.08 ng/ml X h (escape, P less than 0.05). The escape phenomenon was not associated with a significant change in mean arterial pressure or glomerular filtration rate. This study demonstrates that mineralocorticoid escape is temporally related to a significant increase in circulating ANP.
Assuntos
Fator Natriurético Atrial/sangue , Fludrocortisona/farmacologia , Natriurese/efeitos dos fármacos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Tolerância a Medicamentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Masculino , Renina/sangueRESUMO
Hallucinations are defined as sensory phenomena in the absence of external sensory stimuli. Auditory hallucinations have been shown to arise from many different intracranial lesions, but seizures manifesting as musical hallucinations triggered by unruptured intracranial aneurysms are rare. We present a case of persistent, episodic musical hallucinations associated with seizures that led to the discovery of 2 small intracranial aneurysms. Typical electroencephalographic findings for seizure activity were observed but resolved after surgical clipping of the aneurysms. Concomitantly, the patient's hallucinations resolved. The literature on musical hallucinations is reviewed.
Assuntos
Alucinações/etiologia , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico , Convulsões/etiologia , Angiografia Cerebral , Diagnóstico Diferencial , Eletroencefalografia , Feminino , Seguimentos , Alucinações/diagnóstico , Humanos , Aneurisma Intracraniano/cirurgia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Música , Convulsões/diagnóstico , Resultado do TratamentoRESUMO
OBJECTIVE: To determine why some patients have no improvement after surgical treatment of lumbar spinal stenosis. DESIGN: We conducted a retrospective study of patients who were referred to our institution between 1990 and 1993 because their symptoms were unchanged or worsened after lumbar decompressive laminectomy. MATERIAL AND METHODS: For the 45 study patients (25 women and 20 men; mean age, 70.8 years), preoperative and postoperative clinical status, preoperative and postoperative imaging studies, and operative reports were analyzed. RESULTS: Preoperatively, only 23 patients (51%) had the clinical syndrome of neurogenic claudication, and 15 (33%) had midline low-back pain without a radicular component. Three other patients had peripheral neuropathy, and three had atypical leg pain. Only 10 patients had radiographic evidence of severe lumbar canal stenosis; the others had moderate, mild, or no stenosis. In 10 patients, surgical decompression was inadequate. Only three patients had the triad of neurogenic claudication, radiographically confirmed severe lumbar stenosis, and adequate decompression of the lumbar canal and lateral recesses. CONCLUSION: The most common pattern in patients with early failure after lumbar laminectomy was the absence of actual neurogenic claudication coupled with the absence of severe stenosis on preoperative imaging studies. The most common technical error was inadequate neural decompression. These data suggest that the outcome may be improved by more careful selection of patients and by performance of an adequate surgical decompression.
Assuntos
Laminectomia , Estenose Espinal/cirurgia , Idoso , Feminino , Humanos , Laminectomia/métodos , Masculino , Seleção de Pacientes , Complicações Pós-Operatórias , Estudos Retrospectivos , Falha de TratamentoRESUMO
OBJECTIVE: To provide further validation of the treadmill test by assessing its "test-retest" reproducibility. PATIENTS AND METHODS: In this prospective study, 28 patients with severe lumbar spinal stenosis underwent exercise treadmill testing, first at a walking speed of 1.2 mph and then at the patient's preferred walking speed. All patients had a second treadmill examination or "retest." No treatment intervention was performed between the initial test and the retest. Time to first symptoms (TFS) and total ambulation time (TAT) were measured. Differences between the baseline examination and the retest examination were assessed by using the concordance correlation coefficient (CCC) as well as graphically. RESULTS: There was good reproducibility between baseline test and retest results for all 4 end points: 1.2 mph, TFS (CCC = 0.90); 1.2 mph, TAT (CCC = 0.89); preferred walking speed, TFS (CCC = 0.98); and preferred walking speed, TAT (CCC = 0.96). The median difference between trials was not significantly different from zero for any of the 4 outcomes. CONCLUSIONS: Exercise treadmill testing has good test-retest reproducibility. There was no learning phenomenon associated with the test procedure. The study further validates the clinical utility of exercise treadmill testing in patients with lumbar spinal stenosis and neurogenic claudication.
Assuntos
Teste de Esforço , Vértebras Lombares/fisiopatologia , Estenose Espinal/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço/estatística & dados numéricos , Feminino , Humanos , Laminectomia , Aprendizagem , Perna (Membro)/inervação , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Parestesia/etiologia , Doenças do Sistema Nervoso Periférico/complicações , Estudos Prospectivos , Estenose Espinal/cirurgia , Estatísticas não Paramétricas , Fatores de Tempo , Caminhada/fisiologiaRESUMO
The effects of endothelin-1 (ET-1) infusion at 0, 25, 50, and 75 ng/kg/min on blood glucose, insulin, and ET-1 levels were determined in anesthetized rats. In a separate group of rats, ET-1 was infused at 75 ng/kg/min and glucagon and glucose levels were determined. In another group of rats, the effect on blood glucose of glucagon infusion at 0.2 ng/kg/min with ET-1 infusion at 75 ng/kg/min for 30 minutes was determined. Glucose decreased 10 minutes after initiation of ET-1 infusion at 75 ng/kg/min and at 15 minutes during ET-1 infusion at 25 and 50 ng/kg/min. After 45 minutes, glucose decreased by 1.05 +/- 0.1, 1.44 +/- 0.11, and 1.39 +/- 0.22 mmol/L and ET-1 increased by 4.4 +/- 0.8, 5.2 +/- 1.2, and 11.2 +/- 0.8 pmol/L during ET-1 infusion at 25, 50, and 75 ng/kg/min, respectively. Insulin levels increased during ET-1 infusion of 50 ng/kg/min at 30 and 45 minutes by 300 +/- 75 and 405 +/- 120 pmol/L, respectively. During ET-1 infusion of 75 ng/kg/min, insulin increased at 45 minutes by 570 +/- 180 pmol/L. Glucagon decreased during ET-1 infusion at 15 minutes associated with a decrease in glucose. Glucagon levels subsequently returned to baseline values despite a continued decline in glucose levels. Glucagon infusion at 0.2 microgram/kg/min prevented the early ET-1-induced hypoglycemia. These findings demonstrate that ET-1 decreased blood glucose initially associated with a decrease in glucagon and subsequently associated with enhanced insulin release.
Assuntos
Glicemia/análise , Endotelinas/farmacologia , Glucagon/sangue , Glucose/metabolismo , Insulina/sangue , Animais , Masculino , Radioimunoensaio , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
We have previously demonstrated that endothelin-1 (ET-1) increases plasma insulin and decreases blood glucose. The present study was designed to determine if ET-1-induced hypoglycemia occurs in the presence of the insulin secretion inhibitor, somatostatin, and whether ET-1-induced insulin secretion is affected by the nitric oxide synthase I inhibitor, NG-methyl-L-arginine (NMLA), in the anesthetized rat. ET-1 increased plasma insulin and decreased blood glucose in all protocols. Somatostatin alone decreased blood glucose and plasma insulin. Somatostatin blocked ET-1-induced plasma insulin release but did not completely block ET-1-induced hypoglycemia. NMLA alone decreased blood glucose and plasma insulin. NMLA also blocked ET-1-induced insulin release but not ET-1-induced hypoglycemia. The present study confirms our previous finding that ET-1 decreases blood glucose and increases plasma insulin. Because hypoglycemia occurs during insulin inhibition with somatostatin, the present study suggests that ET-1-induced hypoglycemia is partially caused by non-insulin-mediated mechanisms. Because insulin secretion is blocked by nitric oxide synthase I inhibitor, NMLA, the present study suggests that ET-1-induced insulin release may be mediated by production of nitric oxide.
Assuntos
Arginina/análogos & derivados , Glicemia/metabolismo , Endotelinas/farmacologia , Hipoglicemia/induzido quimicamente , Insulina/sangue , Somatostatina/farmacologia , Animais , Arginina/farmacologia , Hipoglicemia/prevenção & controle , Antagonistas da Insulina/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , ômega-N-MetilargininaRESUMO
Inguinal lymphadenitis is associated with a well-defined group of etiologic agents including many sexually transmitted diseases and nonvenereal agents including Yersinia pestis (bubonic plague). We report herein the first case of a second Yersinia species--Yersinia enterocolitica--presenting like bubonic plague with bilateral inguinal lymphadenitis.
Assuntos
Linfadenite/microbiologia , Yersiniose/microbiologia , Idoso , Diabetes Mellitus Tipo 1/complicações , Virilha , Humanos , Masculino , Yersinia enterocoliticaRESUMO
Three studies are reported that show that health-relevant information (e.g., blood pressure [BP] or symptoms) initiates an active cognitive search process that results in the construction of an illness representation. Study 1 showed that informing subjects that their BP was elevated affected two attributes of illness representation: identity (label and symptoms), and time line or expected chronology of the health threat. Subjects given a high-BP reading reported symptoms commonly associated with high BP, especially if they attributed the high-BP reading to stress. Study 2 showed that the active search process uses causal information (a third attribute of representations) to give meaning to symptoms. Specifically, subjects used environmental cues to interpret whether familiar, unfamiliar, and ambiguous symptoms were due to illness or to stress. In Study 3 we showed that the constructive process, initiated by a high-BP reading, is directed by prior beliefs about the time line for developing high BP and by the presence of external cues about the stressfulness of the subject's daily life. Subjects who believed BP was labile and that they were under high daily stress or who believed BP was stable and that they were under low daily stress reported more symptoms. The significance of these findings for understanding how people process diagnostic labels and symptom information involved in the construction of illness representations is discussed.
Assuntos
Nível de Alerta , Papel do Doente , Adulto , Pressão Sanguínea , Diabetes Mellitus/psicologia , Humanos , Hipertensão/psicologia , Mononucleose Infecciosa/psicologia , Controle Interno-Externo , Cooperação do Paciente , Transtornos Somatoformes/psicologia , Estresse Psicológico/complicaçõesRESUMO
How adolescents' personal sense of directedness (i.e., peer, parent, or self-directed orientation) affects the decision-making processes of adolescent students regarding AIDS-related knowledge, attitudes, beliefs, behaviors, and skills (KABBS) is examined. The sample consisted of 10th-grade students in 8 public high schools (N = 2,515) in Dade County (greater Miami), Florida. The findings showed that decision-making orientation and directedness was a significant predictor of AIDS-related KABBS of adolescents. Overall, the level of AIDS-related KABBS that were associated with low risk was found significantly more often among self-directed students and least often among peer-directed students. The findings of this study suggest that future preadult health-risk research should incorporate the concept of differences of information processing across adolescents.
Assuntos
Síndrome da Imunodeficiência Adquirida/prevenção & controle , Negro ou Afro-Americano/psicologia , Tomada de Decisões , Conhecimentos, Atitudes e Prática em Saúde , Hispânico ou Latino/psicologia , Psicologia do Adolescente , População Branca/psicologia , Adolescente , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Grupo Associado , Fatores de Risco , Comportamento SexualRESUMO
This article has discussed the classic hormonal causes of hypertension. Pheochromocytoma and hyperaldosteronism have been discussed, and a clinical approach to evaluation of patients for these problems has been presented. Other humeral factors that influence volume pressure homeostasis have been discussed. It is likely that pharmacologic agents affecting these other factors will become available to patients with hypertension in the future.
Assuntos
Hiperaldosteronismo , Hipertensão/etiologia , Feocromocitoma , Animais , Homeostase/fisiologia , Humanos , Hiperaldosteronismo/classificação , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Resistência à Insulina , Feocromocitoma/complicações , Feocromocitoma/metabolismo , Feocromocitoma/fisiopatologia , Renina/fisiologiaRESUMO
Endogenous opioids have been implicated as a cause of secondary damage after neural injury. The basis for this statement is primarily indirect evidence from studies that demonstrate neurological or physiological improvement when opiate antagonists are given. This study directly evaluates the level of the endogenous opioid beta-endorphin in 15 patients with severe head injury. Levels of immunoreactive beta-endorphin (ir-beta E) from ventricular cerebrospinal fluid (vCSF) and serum were determined less than 24 hours after trauma. No significant correlation was found with the degree of initial injury, age, sex, or either 6- or 12-month outcome. Levels of ir-beta E from vCSF were significantly lower in patients who had received intravenous administration of morphine sulfate (48.4 +/- 5.8 versus 85.9 +/- 10.1 pg/ml, P = 0.008). No correlation was found between vCSF levels of ir-beta E and elapsed time after injury. Although vCSF and serum ir-beta E were correlated (r = 0.532, P = 0.050), the latter exhibited a different profile; the mean level of serum ir-beta E was not significantly different in those patients who received morphine, and serum ir-beta E had a significant negative correlation with time after injury (r = -0.587, P = 0.03). These results do not support a relationship between acute levels of vCSF or serum ir-beta E and the degree of neurological injury or outcome after severe head trauma. This article, therefore, is a contribution to the body of literature in which the purported detrimental effect of beta-endorphin was not demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)