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Clinical management of deliberate self-harm in young people: the need for evidence-based approaches to reduce repetition.

OBJECTIVE: To examine the evidence for the effectiveness of clinical interventions designed to reduce the repetition of deliberate self-harm (DSH) in adolescents and young adults. METHODS: Electronic databases were searched for papers describing randomised and clinical control trials (RCTs) and quasi-experimental studies of interventions targeting adolescents and young adults presenting to clinical services following DSH or suicidal ideation. RESULTS: Three RCTs, four clinical control trials and three quasi-experimental studies were identified. Group therapy, trialled in a RCT, was the only specific programme which led to a significant reduction in rates of repetition of self-harm. Attendance at follow-up did not improve significantly regardless of the intervention, while one clinically controlled trial of intensive intervention resulted in poorer attendance at follow-up. One quasi-experimental study of family therapy resulted in a significant reduction in suicidal ideation. CONCLUSIONS: The evidence base for treatments designed to reduce the repetition of self-harm in adolescents and young adults is very limited. Expensive interventions such as intensive aftercare offer no clear benefit over routine aftercare. Given that deliberate self-harm among young people is a common clinical problem further good quality treatment studies are warranted. Careful consideration should be given to process evaluation to determine which individual components of any given intervention are effective.

Adolescent↗

Using benefit harm tradeoffs to estimate sufficiently important difference: the case of the common cold.

CONTEXT: The term "sufficiently important difference" (SID) refers to the overall amount of benefit that people consider sufficient to justify the costs and risks of treatment. Little is known about patient preferences regarding benefits and harms of common cold treatments. OBJECTIVES: To develop methods to assess SID and to estimate SID for common cold. DESIGN: The authors conducted in-person and telephone interviews with people with colds, using benefit harm tradeoff methods. The hypothetical benefit of reduction in length of illness was traded off against best estimates of costs and risks. First, the authors briefly described costs, risks, and possible symptomatic benefits of 4 treatment scenarios, based on evidence regarding vitamin C, echinacea, zinc, and pleconaril, an antiviral. Hypothetical benefit (reduction of illness duration) was then varied until the cold sufferer indicated that the treatment was minimally desirable. PARTICIPANTS: Interviews were conducted in person with 149 community-recruited adult participants, once at the beginning of their colds, and then again within a few days after symptoms had resolved. Additionally, 162 adult callers with self-identified colds completed interviews via telephone. RESULTS: A total of 460 benefit harm tradeoff interviews (1840 treatment scenarios) estimated overall mean SID as 52.6 h (95% CI, 50.6 to 54.6). For the scenario based on vitamin C, mean SID was estimated as 26.1 h (95% CI, 23.2 to 29.3), with 142 of 460 (31%) saying they would take it regardless of duration benefit, and 22 of 460 (5%) saying they would not take it, regardless of duration benefit. For the echinacea-based scenario, mean SID was estimated at 36.8 h (33.4 to 40.2), with 105 (23%) favoring and 41 (9%) rejecting treatment, regardless of duration benefit. For the zinc lozenge-based scenario, mean SID was estimated as 64.8 h (61.0 to 67.9), with 42 (9%) favoring and 109 (24%) rejecting treatment. For the prescription antiviral-based scenario, mean SID was estimated as 82.6 h (78.7 to 86.7), with 29 (6%) favoring and 223 (48%) rejecting. Severity of illness at the time of interview did not appear to significantly influence responses. Possible side effects, treatment type (tablet v. lozenge v. liquid), monetary costs, and opportunity costs (e.g., getting to the doctor or pharmacy, dosing frequency) did appear to be important in influencing these preference patterns. CONCLUSIONS: Our study suggests that, on average, people want the duration of their colds to be reduced by between 26 and 65 h to justify potential harms of popular cold treatments. A prescription antiviral would require a greater benefit (83 h) to justify larger perceived risks.

Adult↗

Yolk and serum cholesterol and production traits, as affected by incorporating a supraoptimal amount of copper in the diet of the leghorn hen.

1. An experiment was conducted to investigate the possibility of lowering the yolk cholesterol of the egg by supplementing the diet with supraoptimal amounts of copper (50, 150 or 250 mg/kg) as sulphate or acetate. 2. A significant reduction in egg production and a negative effect on food conversion was found when 250 mg/kg of copper was added compared to the control (no added copper). Acetate seemed significantly less harmful in both cases. 3. A significant linear reduction was found in plasma and yolk cholesterol (20% and 14%) and in plasma and yolk triglycerides (24% and 30%) as the dietary copper content was increased from 0 to 250 mg/kg. 4. Regardless of type or quantity of copper, cholesterol and lipids were decreased linearly as birds remained longer on the treatments. A significant interaction between quantity and period showed a greater reduction at a later time. 5. If slightly lower egg production can be accepted, the addition of 250 mg/kg copper might be beneficial in reducing the cholesterol content of the yolk.

Animal Feed↗

Periodic health examination, 1999 update: 1. Detection, prevention and treatment of obesity. Canadian Task Force on Preventive Health Care.

OBJECTIVES: (1) To evaluate the evidence relating to the effectiveness of methods to prevent and treat obesity, and (2) to provide recommendations for the prevention and treatment of obesity in adults aged 18 to 65 years and for the measurement of the body mass index (BMI) as part of a periodic health examination. OPTIONS: In adults with obesity (BMI greater than 27) management options include weight reduction, prevention of further weight gain or no intervention. OUTCOMES: The long-term (more than 2 years) effectiveness of (a) methods to prevent obesity and (b) methods to treat obesity. EVIDENCE: MEDLINE was searched for articles published from 1966 to April 1998 that related to the prevention and treatment of obesity; additional articles were identified from the bibliographies of review articles and the listings of Current Contents. Selection criteria were used to limit the analysis to prospective studies with at least 2 years' follow-up. BENEFITS, HARM AND COSTS: Health benefits of weight reduction were evaluated in terms of alleviation of symptoms, improved management of obesity-related diseases and a reduction in major clinical outcomes. The health risk of weight-reduction methods were briefly evaluated in terms of increased mortality and morbidity. VALUES: The recommendations of this report reflect the commitment of the Canadian Task Force on Preventive Health Care to provide a structured, evidence-based appraisal of whether a manoeuvre should be part of a periodic health examination. RECOMMENDATIONS: (1) PREVENTION: There is insufficient evidence to recommend in favour of or against community-based obesity prevention programs; however, because of considerable health risks associated with obesity and the limited long-term effectiveness of weight-reduction methods, the prevention of obesity should be a high priority for health care providers (grade C recommendation). (2) TREATMENT: (a) For obese adults without obesity-related diseases, there is insufficient evidence to recommend in favour of or against weight-reduction therapy because of a lack of evidence supporting the long-term effectiveness of weight-reduction methods (grade C recommendation); (b) for obese adults with obesity-related diseases (e.g., diabetes mellitus, hypertension), weight reduction is recommended because it can alleviate symptoms and reduce drug therapy requirements, at least in the short term (grade B recommendation). (3) Detection: (a) for people without obesity-related diseases, there is insufficient evidence to recommend the inclusion or exclusion of BMI measurement as part of a periodic health examination, and therefore BMI measurement is left to the discretion of individual health care providers (grade C recommendation); (b) for people with obesity-related diseases, BMI measurement is recommended because weight reduction should be considered with a BMI of more than 27 (grade B recommendation). VALIDATION: The findings of this analysis were reviewed through an iterative process by the members of the Canadian Task Force on Preventive Health Care. SPONSORS: The Canadian Task Force on Preventive Health Care is funded through a partnership between the Provincial and Territorial Ministries of Health and Health Canada.

Adolescent↗

Standards for polysomnography in Canada. The Standards Committees of the Canadian Sleep Society and the Canadian Thoracic Society.

OBJECTIVE: To develop standards for polysomnography in Canada in order to assist in the uniform provision of diagnostic and therapeutic services related to sleep disorders. OPTIONS: Uniform testing versus no current Canadian standards. OUTCOMES: Uniform delivery of health care; reduction in number of repeat studies and their attendant costs. EVIDENCE: Availability of diagnostic laboratories and services, and survey responses (written and oral) from directors of sleep laboratories; the American Thoracic Society statement on indications and standards for cardiopulmonary sleep studies was used as a template. VALUES: Acceptable standards of practice were based on consensus opinion of the standards committees of the Canadian Sleep Society and the Canadian Thoracic Society. The committees comprised specialists in neurology, psychiatry, psychology, respirology and polysomnographic technology; family practitioners and otolaryngologists were also consulted. BENEFITS, HARMS, COSTS: Improved level of care and reduction in duplicate or unnecessary testing; establishment, with available resources, of diagnostic sleep laboratories by appropriately qualified physicians in areas where polysomnography is unavailable. RECOMMENDATIONS: Health care practitioners involved in the diagnosis and treatment of sleep disorders should possess a minimum amount of training (both clinical and research) in sleep disorders medicine. The variables recorded and findings entered in a patient's report must be relevant to the sleep disorder under investigation. The recording equipment must provide reliable, accurate and reproducible data and lend itself to appropriate calibration and quality-control procedures. Facilities for sleep studies must meet patient care safety standards, with provisions for emergency or resuscitative measures when necessary; all personnel must be trained in basic cardiopulmonary resuscitation. VALIDATION: No previous standards concerning polysomnography in Canada exist. The recommended standards were reviewed by all members of the Canadian Sleep Society and a revised document was approved by the Standards Committee of the Canadian Sleep Society and by the Standards and Executive committees of the Canadian Thoracic Society. SPONSORS: These standards are endorsed by the Canadian Sleep Society and the Canadian Thoracic Society. The cost of preparing this statement was borne by the individual members of the standards committees; no external funding was provided.

Calibration↗

Predictors of the excessive mortality rates of dialysis patients in the United States.

It is now well recognized that the United States has the highest mortality rate for end-stage renal disease patients receiving dialysis among the industrialized nations. The possible causes of this almost 25% gross mortality rate (23.6% in 1992) are becoming clearer. After numerous investigations of the various possibilities, it is now evident that the causes are multifactorial. Basically, the US reimbursement for dialysis payment rate has been kept low (essentially no increase since 1973) by allowing inflation to advance and maintaining the actual costs. The industry has responded in a number of ways, some of which have proven harmful. For example, the reuse of dialyzers was probably reasonable and has not proven to be a problem: reductions in staff for older and sicker populations has probably been harmful to the patient's well being; and the shortening of dialysis treatments may have produced more problems than any other change. Essentially, as patients receive less dialysis they feel worse and lose their appetite, thus resulting in weight loss. Frequently dialysis is reduced further because of reduction in certain chemical markers, eg, blood urea nitrogen, that nephrologists use as clinical measurements. This results in a malnourished patient with a low serum albumin level. It is believed but not yet proven that an increase in the dialysis prescription, ie, more dialysis, can reverse this decline. Currently the United States faces the challenges of reducing its mortality rate for end-stage renal disease patients to compare with that of other industrial countries while remaining at the current reimbursement rate, which is less than half that of Germany and one quarter that of Japan.

Humans↗

Lifestyle modifications to prevent and control hypertension. 7. Recommendations on stress management. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada.

OBJECTIVE: To provide updated evidence-based recommendations for health care professionals concerning the effects of stress management on the prevention and control of hypertension in otherwise healthy adults (except pregnant women). OPTIONS: Alternatives to stress management include other nonpharmacologic interventions and medical therapy; these options are not mutually exclusive. OUTCOMES: The health outcome considered was reduction of blood pressure. There is little evidence to date that stress management prevents death or vascular events. Because of insufficient evidence, no economic outcomes were considered. EVIDENCE: A systematic search of the literature (which yielded, among other sources, 3 meta-analyses) was conducted for the period 1966-1997 with the terms essential hypertension, treatment, psychological, behavioural, cognitive, relaxation, mediation, biofeedback and stress management. Other relevant evidence was obtained from the reference lists of the articles identified, from the personal files of the authors and through contacts with experts. The articles were reviewed, classified according to study design and graded according to level of evidence. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and premature death caused by uncontrolled hypertension. BENEFITS, HARMS AND COSTS: The magnitude of the reduction in blood pressure obtained with multicomponent, individualized cognitive behavioural intervention for stress management was comparable in some studies to that obtained with weight loss or drugs; single-component interventions such as biofeedback or relaxation were less effective. The adverse effects of stress-management techniques are minimal, but the cost for effective interventions is substantial, similar initially to drug costs; continuing costs are probably minimal. RECOMMENDATIONS: (1) In patients with hypertension, the contribution of stress should be considered. (2) For hypertensive patients in whom stress appears to be an important issue, stress management should be considered as an intervention. Individualized cognitive behavioural interventions are more likely to be effective than single-component interventions. VALIDATION: These recommendations were reviewed by all of the sponsoring organizations and by participants in a satellite symposium of the fourth International Conference on Preventive Cardiology. They have not been clinically tested. SPONSORS: The Canadian Hypertension Society, the Canadian Coalition for High Blood Pressure Prevention and Control, the Laboratory Centre for Disease Control at Health Canada, and the Heart and Stroke Foundation of Canada.

Adult↗

Number needed to treat (or harm).

The effect of a treatment versus controls may be expressed in relative or absolute terms. For rational decision-making, absolute measures are more meaningful. The number needed to treat, the reciprocal of the absolute risk reduction, is a powerful estimate of the effect of a treatment. It is particularly useful because it takes into account the underlying risk (what would happen without the intervention?). The number needed to treat tells us not only whether a treatment works but how well it works. Thus, it informs health care professionals about the effort needed to achieve a particular outcome. A number needed to treat should be accompanied by information about the experimental intervention, the control intervention against which the experimental intervention has been tested, the length of the observation period, the underlying risk of the study population, and an exact definition of the endpoint. A 95% confidence interval around the point estimate should be calculated. An isolated number needed to treat is rarely appropriate to summarize the usefulness of an intervention; multiple numbers needed to treat for benefit and harm are more helpful. Absolute risk reduction and number needed to treat should become standard summary estimates in randomized controlled trials.

Confidence Intervals↗

Clinical strategies for breast cancer screening: weighing and using the evidence.

When balancing the benefits of screening women for breast cancer against the harms and costs of such screening, one needs to consider the risk for dying of breast cancer, the relative reduction in that risk that will result from screening women in different age groups, and the harms and costs associated with screening. Seven randomized controlled trials provide evidence of the relative risk reduction that results from screening women in different age groups; other studies estimate the harms and costs of screening. These studies indicate that the benefit of screening, expressed as the absolute number of lives extended per 1000 women screened, increases with age and that the harm of screening, expressed as the number of follow-up procedures per cancer detected, decreases with age. Thus, the tradeoff between the benefits and the harms and costs of screening is better for older than for younger women. Because there is no clear cut-point for determining when benefits outweigh harms and costs, it is important to involve women in discussions of breast cancer screening. The women who most need to be involved are those for whom the benefits of screening clearly outweigh the harms and costs and those for whom the benefits and the harms and costs constitute a "close call." For women in both groups, the physician should routinely raise the issue of screening, first eliciting the patient's perceptions and then providing information and discussion about the risk for breast cancer and about the benefits and the harms and costs of screening. Furthermore, the physician should encourage the patient to use her own values to weigh the benefits against the harms and costs, pointing out biases in reasoning and minimizing socioeconomic barriers. Finally, when the benefits obviously outweigh the harms and costs, the physician should make a clear recommendation for screening.

Age Factors↗

Prevention of deaths from harmful drinking in the United States: the potential effects of tax increases and advertising bans on young drinkers.

OBJECTIVE: Harmful alcohol consumption is a leading cause of death in the United States. The majority of people who die from alcohol use begin drinking in their youth. In this study, we estimate the impact of interventions to reduce the prevalence of drinking among youth on subsequent drinking patterns and alcohol-attributable mortality. METHOD: We first estimated the effect of public health interventions to decrease harmful drinking among youth from literature reviews and used life table methods to estimate alcohol-attributable years of life lost by age 80 years among the cohort of approximately 4 million U.S. residents aged 20 in the year 2000. Then, from national survey data on transitions in drinking habits by age, we modeled the impact of interventions on alcohol-attributable mortality. RESULTS: A tax increase and an advertising ban were the most effective interventions identified. In the absence of intervention, there would be 55,259 alcohol-attributable deaths over the lifetime of the cohort. A tax-based 17% increase in the price of alcohol of dollar 1 per six pack of beer could reduce deaths from harmful drinking by 1,490, equivalent to 31,130 discounted years of potential life saved or 3.3% of current alcohol-attributable mortality. A complete ban on alcohol advertising would reduce deaths from harmful drinking by 7,609 and result in a 16.4% decrease in alcohol-related life-years lost. A partial advertising ban would result in a 4% reduction in alcohol-related life-years lost. CONCLUSIONS: Interventions to prevent harmful drinking by youth can result in reductions in adult mortality. Among interventions shown to be successful in reducing youthful drinking prevalence, advertising bans appear to have the greatest potential for premature mortality reduction.

Adult↗

Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts.

BACKGROUND: Ranolazine is a novel antianginal agent that may reduce symptoms without affecting hemodynamics and has shown cardiac antiischemic effects in in vivo and in vitro models. In one study it increased active pyruvate dehydrogenase (PDHa). Other agents that increase PDHa and so increase glucose and decrease fatty acid (FA) oxidation are beneficial in ischemic-reperfused hearts. Effects of ranolazine on glucose and palmitate oxidation and glycolysis were assessed in isolated rat hearts. METHODS AND RESULTS: Working hearts were perfused with Krebs-Henseleit buffer plus 3% albumin under normoxic conditions and on reperfusion after 30-minute no-flow ischemia and under conditions designed to give either low [low (Ca) (1.25 mmol/L), high [FA] (1.2 mmol/L palmitate; with/without insulin] or high (2.5 mmol/L Ca, 0.4 mmol/L palmitate; with/without pacing) glucose oxidation rates; Langendorff-perfused hearts (high Ca, low FA) were subjected to varying degrees of low-flow ischemia. Glycolysis and glucose oxidation were measured with the use of [5-3H/U-14C]-glucose and FA oxidation with the use of [1-14C]- or [9,10-3H]-palmitate. In working hearts, 10 micromol/L ranolazine significantly increased glucose oxidation 1.5-fold to 3-fold under conditions in which the contribution of glucose to overall ATP production was low (low Ca, high FA, with insulin), high (high Ca, low Fa, with pacing), or intermediate. In some cases, reductions in FA oxidation were seen. No substantial changes in glycolysis were noted with/without ranolazine; rates were approximately 10-fold glucose oxidation rates, suggesting that pyruvate supply was not limiting. Insulin increased basal glucose oxidation and glycolysis but did not alter ranolazine responses. In normoxic Langendorff hearts (high Ca, low FA; 15 mL/min), all basal rates were lower compared with working hearts, but 10 micromol/L ranolazine similarly increased glucose oxidation; ranolazine also significantly increased it during flow reduction to 7, 3, and 0.5 mL/min. Ranolazine did not affect baseline contractile or hemodynamic parameters or O2 use. In reperfused ischemic working hearts, ranolazine significantly improved functional outcome, which was associated with significant increases in glucose oxidation, a reversal of the increased FA oxidation seen in control reperfusions (versus preischemic), and a smaller but significant increase in glycolysis. CONCLUSIONS: Beneficial effects of ranolazine in cardiac ischemia/reperfusion may be due, at least in part, to a stimulation of glucose oxidation and a reduction in FA oxidation, allowing improved ATP/O2 and reduction in the buildup of H+, lactate, and harmful fatty acyl intermediates.

Acetanilides↗

Crown contours and gingival response.

The following periodontal/restorative interrelations should be observed: 1. Deflective contours and/or overcontouring should be avoided in the cervical third and the interproximal surfaces of tooth restorations. 2. Overcontouring of the interproximal region is common and harmful to periodontal health. 3. Adequate tooth reduction at the gingival margin and interproximally provides for restorative materials and lessens the potential for overcontouring in these critical regions. 4. Fluting or barreling of exposed furcations eliminates plaque shelves and promotes accessibility for hygiene. 5. Minimal disruption within the intracrevicular space during tooth preparation allows a more predictable, favorable periodontal response to satisfactorily contoured restorations.

Crowns↗

Risk factors for encephalopathy and mortality during melarsoprol treatment of Trypanosoma brucei gambiense sleeping sickness.

This paper reviews the incidence of, and risk factors for, drug-induced encephalopathy and mortality (from all causes) during treatment with melarsoprol of 1083 patients with Trypanosoma brucei gambiense sleeping sickness in Nioki hospital (Zaire) between 1983 and 1990. Sixty-four patients (5.9%) developed encephalopathy and 62 (5.7%) died: 43 from reactive encephalopathy and 19 from other causes. Univariate and multivariate analyses showed that the administration of prednisolone reduced significantly the incidence of encephalopathy and mortality during treatment, especially in patients with trypanosomes observed in the cerebrospinal fluid (CSF) and/or with a CSF white blood cell (WBC) count of 100 or more per mm3. The risk of encephalopathy was associated more strongly with the CSF WBC count than with the presence of CSF trypanosomes. In the subgroup of patients with a CSF WBC count of 100 or more mm3, changing the melarsoprol regimen to 3 series of 3 injections instead of 3 series of 4 injections halved the mortality rate during treatment. Treatment of patients who do develop reactive encephalopathy with the heavy metal chelator dimercaprol, in addition to intravenous steroids and anticonvulsants, may be harmful. The data suggest that a further reduction of the total dose of melarsoprol may decrease toxicity without jeopardizing efficacy.

Adolescent↗

An improved method for Southern DNA and Northern RNA blotting using a Mupid-2 Mini-Gel electrophoresis unit.

An improved method for Southern DNA and Northern RNA blotting using the Mupid-2 Mini-Gel System is described. We get sharp and clear bands in Southern and Northern blotting after only 30 min short gel electrophoresis instead of the several hours large gel electrophoresis of conventional methods. The high electrical voltage with a pulse-like current of the Mupid-2 Mini-Gel System also allows reduction of the amount of formaldehyde, a harmful reagent, from the gel running buffer in RNA blotting. This minor modification of DNA and RNA blotting technique enables us to perform the complete experimental procedure more quickly economically in less space, than conventional Southern and Northern blotting, as well as using an extremely small amount of formaldehyde in RNA blotting.

Blotting, Northern↗

Regulation of alternative oxidase activity during phosphate deficiency in bean roots (Phaseolus vulgaris).

Cyanide-resistant respiration was studied in mitochondria isolated from the roots of bean plants (Phaseolus vulgaris L. cv. Złota Saxa) grown hydroponically up to 16 days on a phosphate-sufficient (+P, control) or phosphate-deficient (-P) medium. Western blotting indicated that the alternative oxidase (AOX) was present only in its reduced (active) form, both in phosphate-sufficient and phosphate-deficient roots, but in the latter, the amount of AOX protein was greater. Addition of pyruvate to the isolation, washing and reaction media made mitochondria from +P roots cyanide-insensitive, similar to mitochondria from -P roots. The doubled activity of NAD-malic enzyme (NAD-ME) in -P compared with +P root mitochondria may suggest increased pyruvate production in -P mitochondria. Lower cytochrome c oxidase (COX) activity and no uncoupler effect on respiration indicated limited cytochrome chain activity in -P mitochondria. In -P mitochondria, the oxygen uptake decreased and the level of Q reduction increased from 60 to 80%. With no pyruvate present (AOX not fully activated), inhibition of the cytochrome pathway resulted in an increased level of the ratio of reduced ubiquinone (Qr) to total ubiquinone (Qt) (Qr/Qt) in +P mitochondria, but did not change Qr/Qt in -P mitochondria. When pyruvate was present, the kinetics for AOX were similar in mitochondria from -P and +P roots. It is suggested that AOX participation in -P respiration may provide an acclimation to phosphate deficiency. Stabilization of the ubiquinone reduction level by AOX might prevent the harmful effect of an increased formation of reactive oxygen species.

Journal Article↗

Influence of leptin and insulin on lipid transfer proteins in human hepatoma cell line, HepG2.

AIM: Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism facilitating the transfer and exchange of cholesteryl esters, triglycerides and phospholipids between lipoproteins. In the study presented here, we investigated the influence of two hormones-the adipocyte-derived hormone leptin as well as insulin on the hepatic secretion of both, PLTP and CETP. METHODS: PLTP activity and CETP concentration-measured by exogenous substrate assay and enzyme-linked immunosorbent assay-were determined in supernatant of human hepatoma cell line HepG2 after single or combined exposure to leptin and insulin at physiological and supraphysiological concentrations, respectively. Messenger-RNA of PLTP and CETP was quantified by Northern blot analysis. RESULTS: Leptin suppressed PLTP activity and CETP-concentration by up to 33% and 23%, respectively. Insulin also suppressed PLTP activity by up to 11% and CETP-concentration by up to 16%. In combination, the two hormones had additive suppressive effects for both, PLTP activity and CETP-concentration. Northern blot analysis showed no difference in m-RNA levels after exposure to leptin or insulin. CONCLUSIONS: Leptin and insulin, both known to increase with body fat mass, suppress production of PLTP and CETP in HepG2 cells. When extrapolated to the in vivo situation, this suppressive effect may constitute a mechanism counteracting the potentially harmful action of lipid transfer proteins, particularly reduction of HDL-cholesterol, in conditions frequently associated with increased plasma triglyceride levels such as obesity and insulin resistance.

Blotting, Northern↗

Where are we with recruitment maneuvers in patients with acute lung injury and acute respiratory distress syndrome?

Reduction of tidal volume to limit plateau pressure currently is recommended for the ventilatory management of acute respiratory distress syndrome. However, sufficient evidence now exists to support the fact that excessive reduction in tidal volume may result in harmful alveolar derecruitment depending on the level at which positive end-expiratory pressure is set. The use of recruitment maneuvers has been proposed as an adjunctive lung-protective strategy to reverse low tidal volume-related derecruitment. Many questions remain regarding the basic physiologic principles of recruitment, and, therefore, the optimal way to perform recruitment maneuvers remains unknown. Moreover, apart from physiologic studies suggesting a potential benefit of recruitment maneuver in terms of recruitment and gas exchange, no data are yet available that demonstrate the ability of such a maneuver to improve outcome. In this article, we discuss the physiologic rules governing recruitment and derecruitment and review articles that provide new insights in the field of recruitment maneuver.

Humans↗

Blood selenium concentrations and glutathione peroxidase activity.

Selenium concentrations in children and teenagers without a metabolic disorder eating normal diets (group 1), and young patients with classical phenylketonuria and milder forms of hyperphenylalaninaemia being treated with a diet low in natural protein (group 2) were investigated. There was a strong correlation between blood selenium concentration and age in children in group 1 up to 10 years of age. Blood selenium concentrations and glutathione peroxidase activities were significantly lower in the patients who were receiving diets containing reduced amounts of natural protein, and the differences were more than would be expected for age. When the concentrations of selenium in blood from groups 1 and 2 were compared with glutathione peroxidase activity, a strong association was found when blood selenium concentrations were below 1.26 mumol/l. Reduction in glutathione peroxidase activity may be harmful in the long term, and the addition of selenium to therapeutic diets is recommended.

Adolescent↗