Background: Atherosclerosis begins in childhood and is influenced by risk factors for coronary heart disease (CHD), of which hypercholesterolemia is crucial. The rationale for treating hypercholesterolemia in childhood is to limit atherosclerosis development, for which adherence to a cholesterol-lowering diet is the first-choice therapy. Nevertheless, pharmacological intervention with bile acid-binding resins may be prescribed for patients older than 10 years, mainly those with family history of CHD, multiple risk factors, and/or severe hypercholesterolemia. Resins are effective and tolerable in this population, but their clinical use has been limited because of poor compliance due to unpalatability; other effective cholesterol-lowering drugs have not been recommended in this population because of the potential impact of drug-related adverse effects such as increases in transaminases, myopathies, and gastrointestinal disturbances. Thus, the need for safer, easy-to-take, and effective cholesterol-lowering agents for this population continues. Policosanol is a mixture of higher primary aliphatic alcohols purified from sugar cane wax with cholesterol-lowering effects proven in patients with type II hypercholesterolemia and dyslipidemia due to type 2 diabetes mellitus. Policosanol shows good safety and tolerability profiles, with no evidence of drug-related adverse events (AEs) to date. This background supports the idea that policosanol could be a good candidate for treating hypercholesterolemia in children and adolescents, but it requires clinical demonstration.Objective: This 12-week study was undertaken to investigate the cholesterol-lowering effects and tolerability of policosanol in hypercholesterolemic patients aged 11 to 19 years.Methods: In this randomized, double-blind, placebo-controlled study, after 4 weeks of dietary stabilization, adolescents with type II hypercholesterolemia were randomly assigned (1:1 ratio) to receive placebo or policosanol 5-mg tablets once daily for 12 weeks. Physical examinations were performed, and lipid profiles and blood samples were obtained at baseline and after 6 and 12 weeks of therapy. The treatment was considered effective if mean reductions of low-density lipoprotein cholesterol (LDL-C) were >15%. In addition, the percentages of patients reaching final values of LDL-C <3.4 mmol/L and optimal values of <2.8 mmol/L were also evaluated. The doses were doubled if LDL-C values were ≥3.4 mmol/L after 6 weeks of therapy. The incidence of AEs and compliance with study medications were also evaluated after 6 and 12 weeks of treatment.Results: Fifty-five patients were enrolled in the study (28 policosanol, 27 placebo). Twenty-three patients (17 placebo, 6 policosanol) required dose titration at 6 weeks. After 12 weeks of therapy, policosanol significantly decreased LDL-C with respect to baseline and placebo (both P < 0.001), showing a mean reduction of 32.6%. Total cholesterol (TC) and TC/high-density lipoprotein cholesterol (HDL-C) and LDL-C/HDL-C ratios were reduced by 21.9%, 27.8%, and 37.2%, respectively, in the policosanol group (P < 0.001, compared with baseline and placebo). HDL-C rose 10.1% (P < 0.001), compared with baseline and placebo. Triglycerides were unaffected by policosanol. LDL-C, TC, and both atherogenic ratios were reduced significantly in the policosanol group (P < 0.001), and significant increases in HDL-C values were observed at the 6-week interim checkup (P < 0.001 vs baseline, P < 0.01 vs placebo). Twenty-five (89.3%) of 28 patients in the policosanol group showed LDL-C reductions >15% compared with 2 (7.4%) of 27 patients in the placebo group (P < 0.001). In addition, 26 (92.8%) of 28 policosanol patients reached LDL-C values < 3.4 mmol/L compared with 4 (14.8%) of 27 patients in the placebo group (P < 0.001). Likewise, the response rate for achievement of optimal values (LDL-C < 2.8 mmol/L) was also larger in the policosanol group (20/28; 71.4%) than in the placebo group (0/27; 0.0%) (P < 0.001). Policosanol was well tolerated, with no drug-related effects found on physical examination. Blood biochemistry determinations revealed significantly lower alanine aminotransferase levels in the policosanol group after 6 weeks of therapy compared with placebo (P < 0.05), as well as significant reductions in aspartate aminotransferase levels at 6 weeks (P < 0.01) and 12 weeks (P < 0.05) compared with baseline. No patients withdrew from the study, and only 3 patients (2 placebo, 1 policosanol) experienced mild AEs during the study; the placebo patients reported abdominal pain and constipation (1 each), and the policosanol patient reported polyphagia.Conclusions: Policosanol 5 mg/d appears to be well tolerated and effective as short-term treatment of hypercholesterolemia in adolescents. 相似文献
Pain is the predominant symptom that prompts patients to seek medical advice and treatment from physiotherapists. Various treatment modalities such as heat and cold, electrical stimulation (Cheing and Hui-Chan, 1999), ultrasound, manipulative techniques, massage and laser treatment have been demonstrated in varying degrees to be clinically effective for managing pain of different pathologies. However, all these treatments could be assumed to have some placebo elements (French, 1994).
From a research design perspective, the presence of placebo response is undesirable and must be controlled as it complicates the demonstration of ‘real' treatment effect. From a clinical perspective, it is intriguing to note that the condition of patients in the placebo control groups did improve considerably in many of these validation studies, although in the majority the improvement was not so marked as in the treatment groups. Conspicuously, some neuro-physiological and psychological aspects of the placebo effects may have clinical use in enhancing the effect of pain treatments and their outcomes.
Unfortunately, although placebo response has been a subject of continuing interest among some physiotherapy researchers and clinicians, information about placebo analgesia and its clinical utility is seldom discussed. The purpose of this paper is to provide clinicians with an overview of the construct and research related to placebo analgesia as well as a discussion of the potential clinical use of certain components of placebo analgesia to enhance pain rehabilitation outcomes in physiotherapy practice. 相似文献
Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis. 相似文献
Examining the quality and quantity of food intake by appropriate methods is critical in the management of patients with chronic kidney disease (CKD). The four commonly used dietary assessment methods in CKD patients include short‐term dietary recalls, several days of food records with or without dietary interviews, urea kinetic based estimates such as protein nitrogen appearance calculation, and food histories including food screeners and food frequency questionnaires (FFQ). There are a number of strengths and limitations of these dietary assessment methods. Accordingly, none of the four methods is suitable in and of itself to give sufficiently accurate dietary information for all purposes. Food frequency questionnaires, which is the preferred method for epidemiological studies, should be used for dietary comparisons of patients within a given population rather than individual assessment. Food histories including FFQ and dietary recalls may underestimate important nutrients, especially in CKD patients. Given the large and increasing number of dialysis patients and work responsibilities of renal dietitians, routine analysis of dietary records and recalls is becoming less feasible. Ongoing and future studies will ascertain additional strengths and limitations of dietary assessment methods in CKD populations including the assessment of food intake during an actual hemodialysis treatment. 相似文献
This study assessed factors associated with participation in HIV counseling and testing and reported reasons for not taking
part in Voluntary HIV Counseling and Testing among 930 pregnant women attending clinics for antenatal care in South Africa.
Results indicate that from 930 clients interviewed 87% had agreed to participate in individual pre-test HIV counseling and
81.2% had received their test results in post-test counseling. Fear for taking the test, lack of confidentiality and knowing
one’s HIV status were the main reasons why women refused to test. In multivariable analysis trust of HCT provider was associated
with participation in HIV pre-test counseling and no risky drinking was associated with participation in HIV post-test counseling.
These findings suggest mistrust towards HCT providers should be reduced and screening and brief intervention for alcohol problems
provided. 相似文献
The industrial uses of indium, a rare metal with no known physiological role in humans, have increased dramatically over the past 15 years.The results of animal toxicity studies showing pulmonary and systemic effects as well as some reports in workers have created a growing concern about the possible occurrence of toxic effects in exposed workers. Validated biomarkers to assess exposure to indium are not available.
Objectives
This work aimed at investigating the kinetics of indium in urine (In-U) and plasma (In-Pl) in workers manufacturing In ingots and mainly exposed to hardly water-soluble In compounds. All nine workers from the In department of a large metallurgical concern participated in the study as well as 5 retired workers and 20 controls.
Methods
Personal breathing zone air was collected throughout the work shift on Monday and Friday. Blood and urine samples were collected, before and after the shift, on the same day as the air sampling and on preshift the next Monday after a non-working week-end. Moreover, rats were given either InCl3 by intraperitoneal injection or In2O3 by pharyngeal aspiration, In was followed in plasma during 120 days and measured in tissues 120 days after exposure.
Results
Higher In-Pl and In-U concentrations were found in both current (range 0.32–12.61 μg/L plasma; 0.22–3.50 μg/g creat) and former (0.03–4.38 μg/L plasma; 0.02–0.69 μg/g creat) workers compared with controls (<0.03 μg/L plasma; <0.02 μg/g creat). Both biological parameters were highly correlated but no correlation was found between In-air (10–1030 μg/m3) and In-Pl or In-U. Normalizing In-U by the urinary creatinine concentration reduced the inter- (from 90% to 70%) and intra-individual variability (from 54% to 35%). In-Pl remained remarkably stable along the working week (inter- and intra-individual variability: 89% and 10%, respectively). Neither In-U nor In-Pl significantly increased during the day or the week. A week-end without occupational exposure was not sufficient to reach the background In-Pl and In-U levels measured in controls. The results of the experimental investigations confirmed the hypothesis that inhalation of hardly soluble In compounds may cause accumulation of In in the body leading to a prolonged “endogenous exposure” from both a lung depot of “insoluble” particles that are progressively absorbed and from a retention depot in other internal organs.
Conclusion
This study shows that in workers exposed to hardly soluble In compounds, In-U and In-Pl are very sensitive to detect exposure and mainly reflect long-term exposure. In-Pl levels are particularly stable for a given individual. In-U might be more influenced than In-Pl by recent exposure. Both parameters remained high years after withdrawal from exposure, indicating a possible endogenous exposure and a prolonged risk of pulmonary and systemic diseases even after work exposure has ceased. 相似文献
A field test of integrated vector control was conducted in a tropical urban setting with a combination of a floating, slow-release, granular formulation of Bacillus sphaericus and environmental engineering measures (renovation of roads, collective water pumps, and cesspool lids). The targets were Culex quinquefasciatus and Anopheles gambiae in the two biggest towns of Burkina Faso (West Africa). Within the intervention zone, water pumping stations were improved and the surroundings drained to prevent the accumulation of stagnant water. Roads were leveled and given either simple gutters on each side or a concrete channel on one side to drain runoff water. Garbage containers were installed to provide an alternative to the drainage channels for waste disposal. Septic tanks were modified so that they could be emptied without destroying their lid. This study showed that it is possible to implement mosquito control in a tropical urban environment with teams of young people rapidly trained to apply a biological larvicide without any tools other than an iron bar to lift cesspool lids. Environmental improvements were initially costly, but demanded little subsequent expenditure. Local inhabitants' committees were mobilized to provide people with information and monitor the efficacy of the measures. Compared with what people spent individually on mosquito prevention and malaria medicine, these measures were not expensive, but many expected the community to pay for them from existing taxes, e.g., for water treatment and disposal. The necessary funding and logistics require a municipal organization with neighborhood support, if the measures are to be effective. 相似文献
Acute phosphodiesterase 5A inhibition by sildenafil or EMD360527/5 promoted profound inhibition of the cardiac Na(+)/H(+) exchanger (NHE-1), detected by the almost null intracellular pH recovery from an acute acid load (ammonium prepulse) in isolated papillary muscles from Wistar rats. Inhibition of phosphoglycerate kinase-1 (KT5823) restored normal NHE-1 activity, suggesting a causal link between phosphoglycerate kinase-1 increase and NHE-1 inhibition. We then tested whether the beneficial effects of NHE-1 inhibitors against the deleterious postmyocardial infarction (MI) remodeling can be detected after sildenafil-mediated NHE-1 inhibition. MI was induced by left anterior descending coronary artery ligation in Wistar rats, which were randomized to placebo or sildenafil (100 mg kg(-1) day(-1)) for 6 weeks. Sildenafil significantly increased left ventricular phosphoglycerate kinase-1 activity in the post-MI group without affecting its expression. MI increased heart weight/body weight ratio, left ventricular myocyte cross-sectional area, interstitial fibrosis, and brain natriuretic peptide and NHE-1 expression. Sildenafil blunted these effects. Neither a significant change in infarct size nor a change in arterial or left ventricular systolic pressure was detected after sildenafil. MI decreased fractional shortening and the ratio of the maximum rate of rise of LVP divided by the pressure at the moment such maximum occurs, effects that were prevented by sildenafil. Intracellular pH recovery after an acid load was faster in papillary muscles from post-MI hearts (versus sham), whereas sildenafil significantly inhibited NHE-1 activity in both post-MI and sildenafil-treated sham groups. We conclude that increased phosphoglycerate kinase-1 activity after acute phosphodiesterase 5A inhibition blunts NHE-1 activity and protects the heart against post-MI remodeling and dysfunction. 相似文献