Resting Energy Expenditure and Cold-induced Thermogenesis in Patients With Overt Hyperthyroidism.

CONTEXT: Thyroid hormone (TH) is crucial for the adaptation to cold. OBJECTIVE: To evaluate the effect of hyperthyroidism on resting energy expenditure (REE), cold-induced thermogenesis (CIT) and changes in body composition and weight. METHODS: This was a prospective cohort study at the endocrine outpatient clinic of a tertiary referral center. Eighteen patients with overt hyperthyroidism were included. We measured REE during hyperthyroidism, after restoring euthyroid TH levels and after 3 months of normal thyroid function. In 14 of the 18 patients, energy expenditure (EE) was measured before and after a mild cold exposure of 2 hours and CIT was the difference between EEcold and EEwarm. Skin temperatures at 8 positions were recorded during the study visits. Body composition was assessed by dual X-ray absorption. RESULTS: Free thyroxine (fT4) and free triiodothyronine (fT3) decreased significantly over time (fT4, P = .0003; fT3, P = .0001). REE corrected for lean body mass (LBM) decreased from 42 ±â€…6.7 kcal/24 hour/kg LBM in the hyperthyroid to 33 ±â€…4.4 kcal/24 hour/kg LBM (-21%, P < .0001 vs hyperthyroid) in the euthyroid state and 3 months later to 33 ±â€…5.2 kcal/24 hour/kg LBM (-21%, P = .0022 vs hyperthyroid, overall P < .0001). fT4 (P = .0001) and fT3 (P < 0.0001) were predictors of REE. CIT did not change from the hyperthyroid to the euthyroid state (P = .96). Hyperthyroidism led to increased skin temperature at warm ambient conditions but did not alter core body temperature, nor skin temperature after cold exposure. Weight regain and body composition were not influenced by REE and CIT during the hyperthyroid state. CONCLUSION: CIT is not increased in patients with overt hyperthyroidism.

Assessment of therapeutic biomarkers in the treatment of children with postural tachycardia syndrome and vasovagal syncope.

BACKGROUND: Postural tachycardia syndrome and vasovagal syncope are common causes of orthostatic intolerance in children. The supplementation with water, or salt, or midodrine, or ß-blocker was applied to children with postural tachycardia syndrome or vasovagal syncope. However, the efficacy of such medication varied and was not satisfied. This review aimed to summarise the current biomarkers in the treatment of the diseases. DATA SOURCES: Studies were collected from online electronic databases, including OVID Medline, PubMed, ISI Web of Science, and associated references. The main areas assessed in the included studies were clinical improvement, the cure rate, and the individualised treatment for postural tachycardia syndrome and vasovagal syncope in children. RESULTS: Haemodynamic change during head-up tilt test, and detection of 24-hour urinary sodium excretion, flow-mediated vasodilation, erythrocytic H2S, and plasma pro-adrenomedullin as biological markers were the new ways that were inexpensive, non-invasive, and easy to test for finding those who would be suitable for a specific drug and treatment. CONCLUSION: With the help of biomarkers, the therapeutic efficacy was greatly increased for children with postural tachycardia syndrome and vasovagal syncope.

Management of acute coronary syndromes in developing countries: acute coronary events-a multinational survey of current management strategies.

BACKGROUND: The burden of cardiovascular diseases is predicted to escalate in developing countries. We investigated the descriptive epidemiology, practice patterns, and outcomes of patients hospitalized with acute coronary syndromes (ACS) in African, Latin American, and Middle Eastern countries. METHODS: In this prospective observational registry, 12,068 adults hospitalized with a diagnosis of ACS were enrolled between January 2007 and January 2008 at 134 sites in 19 countries in Africa, Latin America, and the Middle East. Data on patient characteristics, treatment, and outcomes were collected. RESULTS: A total of 11,731 patients with confirmed ACS were enrolled (46% with ST-elevation myocardial infarction [STEMI], 54% with non-ST elevation-ACS). During hospitalization, most patients received aspirin (93%) and a lipid-lowering medication (94%), 78% received a ß-blocker, and 68% received an angiotensin-converting enzyme inhibitor. Among patients with STEMI, 39% did not receive fibrinolysis or undergo percutaneous coronary intervention. All-cause death at 12 months was 7.3% and was higher in patients with STEMI versus non-ST elevation-ACS (8.4% vs 6.3%, P < .0001). Clinical factors associated with higher risk of death at 12 months included cardiac arrest, antithrombin treatment, cardiogenic shock, and age >70 years. CONCLUSIONS: In this observational study of patients with ACS, the use of evidence-based pharmacologic therapies for ACS was quite high, yet 39% of eligible patients with STEMI received no reperfusion therapy. These findings suggest opportunities to further reduce the risk of long-term ischemic events in patients with ACS in developing countries.

Avaliação dos efeitos do betabloqueador nebivolol sobre o peritônio em modelo experimental murino de diálise peritoneal / Assessment of the effects of beta-blocker nebivolol on the peritoneum in an experimental murine model of peritoneal dialysis

A falência de ultrafiltração (UFF) é uma causa importante de interrupção da diálise peritoneal (DP) enquanto terapia renal substitutiva. Além da inflamação crônica e aguda causadas à membrana peritoneal (MP) pelos produtos de degradação da glicose, produtos avançados da glicosilação, pH ácido das soluções e infecções, -bloqueadores (BB) também foram implicados na gênese da UFF. A vasoconstrição arteriolar esplâncnica é considerada a causa provável da UFF por BB. O nebivolol (NV), um bloqueador 1-adrenérgico altamente seletivo que, diferente de outros BB, possui efeito vasodilatador por aumento de óxido nítrico (NO) por ativar a via L-arginina-NO, foi testado em pacientes idosos com ICC e levou à redução na mortalidade. O objetivo desse estudo é analisar os efeitos do NV sobre a ultrafiltração (UF), MP e características do efluente em um modelo animal de DP, através do estudo de fenômenos envolvidos na degeneração da MP e UFF, como transição epitélio mesenquimal (EMT) e fibrose, além de parâmetros humorais e celulares de inflamação. 21 camundongos C57BL/6 fêmeas, não urêmicos, com 12 a 14 semanas, foram submetidos à colocação de cateter peritoneal. Após uma semana, foram divididos em 3 grupos de 7 animais: grupo controle (observação 30 dias), grupo SDP (2 mL/ dia de solução glicosada de diálise peritoneal a 4,25% através do cateter, por 30 dias) e grupo NV (além da infusão, receberam 8 mg/kg/dia de NV por gavagem, por 30 dias). Após 30 dias, comparou-se espessura submesotelial, volume de UF, velocidades de transporte de pequenos solutos, marcação submesotelial de pan-citoqueratina, para quantificar EMT, contagem de vasos, linfangiogênese diafragmática e concentração de IL-6 e IL-10 no efluente...

Ultrafiltration failure (UFF) is a major cause of peritoneal dialysis (PD) discontinuation. Besides peritoneal membrane (PM) acute and chronic inflammation caused by glucose degradation products, advanced glycation end-products, acidic pH of the solutions and peritoneal infections, also -blockers (BBs) have been implicated in UFF genesis. Splanchnic arteriolar vasoconstriction has been considered the probable cause of UFF induced by BBs. Nebivolol (NV), a highly selective 1-adrenergic blocker, unlike other BBs, has a vasodilatory effect caused by its ability to increase nitric oxide (NO) through L-arginine-NO pathway activation. NV has been tested in elderly patients with congestive heart failure and led to mortality reduction. The aim of this work is to analyze the effects of NV over ultrafiltration (UF), PM and effluent characteristics in an animal model of PD. For that end, phenomena known to be involved in PM degeneration and UFF, such as epithelial-to-mesenchymal transition (EMT), fibrosis, as well as cellular and humoral parameters of inflammation have been studied. 21 C57BL/ 6 female non uremic mice, ageing 12 to 14 weeks, underwent peritoneal catheter placement. One week later, they were divided into 3 groups of 7 animals: control group (observation for 30 day), PDF group (2 mL/ day of 4.25% dextrose peritoneal dialysis fluid injected through the catheter for 30 days) and NV group (besides the PDF infusion, this group received 8 mg/ kg/ day of NV by gavage, for 30 days). After 30 days, submesotelial thickness, UF volume, small solute transport speed, submesotelial pan-cytokeratin staining (EMT quantification), vessel count, diaphragmatic lymphangiogenesis and IL-6 and IL-10 concentrations in the effluent were compared. PM thickness was 23.14 m in the control group, 102.4 m in the PDF group and 29.04 m in the NV group, p <0.05...

Scalable synthesis of a prostaglandin EP4 receptor antagonist.

The evolution of scalable, economically viable synthetic approaches to the potent and selective prostaglandin EP4 antagonist 1 is presented. The chromatography-free synthesis of multikilogram quantities of 1 using a seven-step sequence (six in the longest linear sequence) is described. This approach has been further modified in an effort to identify a long-term manufacturing route. Our final synthesis involves no step requiring cryogenic (< -25 degrees C) conditions; comprises a total of four steps, only three of which are in the longest linear synthesis; and features the use of two consecutive iron-catalyzed Friedel-Crafts substitutions.

Additional small amounts of diuretics improve blood pressure control at low cost without disadvantages in blood sugar metabolism.

We evaluated our present treatment of hypertension and sought a way to improve it. We studied 164 of outpatients we treated in 2002. Mean systolic blood pressure (SBP)+/-SD was 142.0+/-11.3, and 56% of patients had SBP over 140 mmHg. We used more diuretics in patients with good control of SBP (19% vs. 7% of patients; p=0.012). After observing our hypertensive patients, we changed our treatment in a goal-oriented manner. Our goal was blood pressure below 140/90 mmHg. We used, in principle, additional small amounts of diuretics for inadequately treated patients. We followed 147 of the 164 patients from 2002 to 2006. During this period, mean SBP decreased to 134.7+/-9.1 mmHg (p<0.001), and the frequency of patients with SBP>140 mmHg decreased to 14% (p<0.001). We used more diuretics in 2006 than in 2002 (12% to 46% p<0.001). To estimate the risks and benefits of diuretics, in 2006 we analyzed 510 patients who had been followed for at least 2 years. Potassium supplementation was needed in 28% of diuretic-treated patients and 7% of patients without diuretics. We found a correlation between the use of diuretics and good SBP control in the entire patient group as well as in patients with diabetes. In the control of diabetes mellitus, we found no statistical difference between patients treated with diuretics and those not. We found diuretics had no adverse effects with respect to new-onset diabetes mellitus.

[Assessment by logistic model of hemodynamic changes during general anesthesia].

The anesthesia induction with strong anesthetic agents generally reduces blood pressure. Cardiovascular agents used during anesthesia induce hemodynamic changes. The time courses of systolic (sBP) and diastolic blood pressure (dBP) and heart rate (HR) are expressed as sigmoidal curve. We have found that the hemodynamic changes can be precisely curve-fitted with a logistic function giving non-linear curve. The four parameters of the logistic function present the first asymptote, the last asymptote, the slope at the inflection point, and the time to the inflection point. Moreover, each logistic parameter is used for the effects of drug dose, age and sex differences of subjects on the hemodynamic change. In this review, we introduce the analyses with the logistic function for the changes in sBP, and dBP during preintubation period and HR, sBP, and dBP during infusion of landiolol hydrochloride, an ultra-short-acting beta1-adrenergic receptor blocking agent, which is used for subjects with tachycardia during general anesthesia. The logistic parameters are useful for assessing the hemodynamic response during general anesthesia. The assessment method of the hemodynamic change using the logistic model contributes much to the management of anesthesia.

Hypertension treatment in a medicare population: adherence and systolic blood pressure control.

BACKGROUND: Despite substantial trial evidence that demonstrates the effectiveness of pharmacologic treatment for reducing blood pressure (BP) and cardiovascular events, many patients are nonadherent to their hypertension treatment. OBJECTIVES: The purpose of this study was to examine patient adherence to hypertension medications using pharmacy data (ie, outpatient, inpatient, and mail-order prescriptions) and the association between adherence measures and systolic BP (SBP) control. METHODS: The study included Medicare + Choice beneficiaries (aged > or = 65 years) who were continuously enrolled in an integrated delivery system in 2003, and who had documented hypertension and received > or = 1 hypertension drug in 2002. This analysis used automated clinical data and the 2000 US Census. We estimated 2 measures of hypertension treatment adherence in 2003 using the supply of dispensed drugs in days (proportion of days covered > or = 80%): (1) adherence to > or = 1 hypertension drug; and (2) adherence to the full hypertension treatment regimen. We defined the regimen by the number of hypertension drugs used concurrently in 2002. We assessed adherence annually and during the 30, 60, and 90 days before an SBP measurement. Logistic regression was used to examine the association between adherence and the number of drugs in the hypertension regimen, as well as the association between adherence and elevated SBP ( > or = 140 mm Hg). We adjusted for patient sociodemographic and clinical characteristics. RESULTS: The majority (52.8%) of patients had multidrug hypertension regimens. In 2003, 87.3% of subjects were adherent to > or = 1 hypertension drug; 72.1% were adherent to their full regimen. After adjustment, we found that subjects with multidrug regimens were significantly more likely to be adherent to > or = 1 drug and significantly less likely to be adherent to their full regimen, compared with patients on a 1-drug regimen. Over one-third of subjects had elevated SBP in 2003. Both adherence measures were associated with lower odds of having elevated SBP (eg, odds ratio = 0.87 [95% CI, 0.84-0.89] for adherence to the full regimen). For subjects with multidrug regimens, partial adherence and nonadherence to the regimen were associated with higher odds of having elevated SBP. CONCLUSIONS: Adherence measures using automated pharmacy data can identify patients who are nonadherent to their drug treatment regimen and who are more likely to have inadequately controlled BP. Adherence measures that account for the number of drugs in a patients' drug regimen might help identify additional patients at risk for poor BP outcomes due to partial treatment adherence.

Assessing military veterans for posttraumatic stress disorder: a guide for primary care clinicians.

PURPOSE: To educate primary care providers on the physical effects of posttraumatic stress disorder (PTSD), explain why military veterans are at great risk, and describe how to identify PTSD in primary care clients. DATA SOURCES: Current scientific and psychiatric literature on PTSD. CONCLUSIONS: PTSD is prevalent in the military community because of the frequency and type of trauma seen in the combat zone. With the ongoing military deployments, assessment for the presence of PTSD is increasingly important for comprehensive and high-quality primary care. Clients with trauma histories, such as veterans, are at increased risk for physical disorders such as heart disease and psychological disorders such as anxiety, depression, and PTSD. IMPLICATIONS FOR PRACTICE: Primary care clinicians, including those outside the military health system, are essential in identifying trauma histories and directing clients to appropriate care.

Comparison of the cost-effectiveness of milnacipran (a SNRI) with TCAs and SSRIs: a modeling approach.

A simulation model based on the theory of clinical decision analysis was used to compare outcomes and costs when treating patients with major depressive episodes using either a selective serotonin re-uptake inhibitor (SSRI) or a tricyclic antidepressant (TCA), in comparison with milnacipran (a serotonin), and a norepinephrine re-uptake inhibitor (SNRI). The clinical data used were taken from published meta-analyses. This analysis supports: (1) a comparable efficacy of milnacipran and TCA with a better tolerance; and, (2) an advantage of milnacipran over SSRI for efficacy with a comparable tolerance. Based on these findings, a decision tree was constructed with the assistance of a panel of psychiatrists in order to provide a model of usual clinical practice. Estimates not available from clinical studies were obtained either from literature analysis or from the panel. Economic appraisal was performed according to the viewpoint of the French national sickness fund (sécurité sociale), and expenditure assessment was limited to direct costs (hospitalizations, antidepressant medications, visits, and laboratory tests). The results suggest that milnacipran is a cost-effective alternative: the expected cost of treatment per depressive episode is lower than either a French representative panel of TCAs (a saving of 288 FF), or SSRIs (a savings of 961 FF). The expected length of clinical remission is slightly higher than comparators. The robustness of these findings was supported by sensitivity analyses.

[Use of antihypertensive drugs in Spain, 1985-1995]. / Uso de antihipertensivos en España, 1985-1995.

BACKGROUND: This study has analysed the trend of antihypertensive drugs consumption in Spain from 1985 to 1995, its economical impact and the correlation with the available scientific evidence. The utilization of calcium channel blockers in the context of the recent controversial about their safety profile was also evaluated. METHODS: Drugs from the ATC groups C02, C03 (excluding C03C), C07, C08 (excluding nimodipine and nicardipine) and C09 were included (ATC classification, 1996 version). Drug utilization data and cost figures were obtained from the databases ECOM and FAR-90 of the Ministry of Health. These databases contain the number of packages sold in community pharmacies that are charged to the National Health System. Data are expressed in defined daily doses per 1,000 inhabitants per day (DHD). The cost is expressed in current and constant pesetas. RESULTS: The use of antihypertensives increased from 34.78 DHD in 1985 to 103.55 DHD in 1995. Angiotensin-converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) are responsible for 89% of the total increase. Thiazides and beta-blockers showed a mild increase, although its relative contribution to the total figures declined from 72 to 32% at the end of the period. Rauwolfia alcaloids and antiadrenergic drugs sales were negligible (0.4% of total sales in 1995). Within the thiazides, consumption was concentrated in products containing > or = 50 mg hydrochlorothiazide or equivalent. Enalapril, captopril, nifedipine and the fixed-dose association of hydrochlorothiazide with amiloride were the most widely used drugs. The cost of antihypertensive drugs in current pesetas raised eight times through the study period reaching 105,501 millions pesetas in 1995; 89% of the cost corresponded to ACEI and CCB. Expressed in constant pesetas the cost increase was four fold. The recent controversia about CCB did not have influence on its consumption. CONCLUSIONS: The pattern of use of antihypertensive drugs in Spain does not follow the available scientific evidence. Drugs with less documented effectiveness are the most prescribed; even considering the same effectiveness, efficiency is lower for drugs with higher utilization rates. The available presentations for thiazides makes their utilization in the optimal dosification difficult.