Transfer of Cholesterol and Other Lipids From a Lipid Nanoemulsion to High-density Lipoprotein in Heart Transplant Patients

Background: Beyond the first year after a heart transplant (HT) procedure, patients often develop dyslipidemias, which may be implicated in the genesis of transplant coronary heart disease. High-density lipoprotein (HDL) has a several anti-atherogenic properties, but the status of HDL in HT patients is still controversial. Nonetheless, determination of HDL cholesterol concentration is not sufficient for evaluation of the overall HDL protective role. In this study, a fundamental functional property of HDL, the ability to simultaneously receive the major lipid classes, was tested in HT patients. Methods: Twenty HT patients and 20 healthy normolipidemic subjects paired for gender, age and body mass index were studied. Blood samples were collected after 12-hour fasting for determination of plasma lipids, glucose, paraxonase I (PON 1) activity, HDL diameter and transfer of labeled lipids from an artificial nanoemulsion to HDL. Results: Plasma triglycerides (159 +/- 63 vs 94 +/- 35 mg/dl) and glucose (104 +/- 20 vs 86 +/- 10 mg/dl) were greater in HT patients than in control subjects. HDL cholesterol was lower and HDL diameter was smaller in the HT group (HDL cholesterol: 44 +/- 11 vs 55 +/- 15 mg/dl; HDL diameter: 8.8 +/- 0.6 vs 9.0 +/- 1.2 nm). PON 1 activity did not differ (87 +/- 47 vs 75 +/- 37 nmol/min/ml). The transfer rates of free cholesterol and cholesteryl esters were diminished in HT patients (HT: 8.4 +/- 1.2% and 3.8 +/- 0.6%; controls: 9.7 +/- 1.9% and 4.7 +/- 1.2%, respectively). Conclusions: The transfer of free cholesterol and cholesteryl esters to HDL is diminished in HT patients; disturbance in the ability of HDL to receive lipids may affect the anti-atherogenic properties of the lipoprotein. J Heart Lung Transplant 2009;28:1075-80. Copyright (C) 2009 by the International Society for Heart and Lung Transplantation.

Employee group memberships and organisational communication during organisational change

The preset study adopted an intergroup approach to information sharing and communication in three organisational samples during change. In Study 1, employees from a public hospital (N = 142) completed a survey measuring perceptions of organisational communication and strength of identification with the work unit and the organisation as a whole. Consistent with predictions, team members rated communication from double ingroup members (same work unit/same occupational group) more favourably than communication from partial group members (same work unit/different occupational group). Also as predicted, work unit identification was related to favourable ratings of work unit communication across occupational groups, whereas occupational identification was related to favourable ratings of work unit communication within occupational groups. In Study 2, strength of identification with three organisational groups was associated with positive ratings of communication among employees from the same public hospital (N = 189) and a military organisation (N = 2119). Based on these results, intergroup strategies for the management of information sharing and organisational communication during change are discussed.

A randomized double-blind placebo-controlled study of the long-term efficacy and safety of diethylpropion in the treatment of obese subjects

Objective: To evaluate the efficacy of diethylpropion on a long-term basis, with emphasis in cardiovascular and psychiatric safety aspects. Design: Randomized, double-blind, placebo-controlled trial Measurements: Following a 2-week screening period, 69 obese healthy adults received a hypocaloric diet and were randomized to diethylpropion 50 mg BID (n = 37) or placebo (n = 32) for 6 months. After this period, all participants received diethylpropion in an open-label extension for an additional 6 months. The primary outcome was percentage change in body weight. Electrocardiogram (ECG), echocardiography and clinical chemistry were performed at baseline and every 6 months. Psychiatric evaluation and application of Hamilton rating scales for depression and anxiety were also performed by experienced psychiatrists at baseline and every 3 months. Results: After 6 months, the diethylpropion group lost an average of 9.8% (s.d. 6.9%) of initial body weight vs 3.2% (3.7%) in the placebo group (P < 0.0001). From baseline to month 12, the mean weight loss produced by diethylpropion was 10.6% (8.3%). Participants in the placebo group who were switched to diethylpropion after 6 months lost an average of 7.0% (7.7%) of initial body weight. The difference between groups at month 12 was not significant (P = 0.07). No differences in blood pressure, pulse rate, ECG and psychiatric evaluation were observed. Dry mouth and insomnia were the most frequent adverse events. Conclusion: Diethylpropion plus diet produced sustained and clinically significant weight loss over 1 year. It seems to be safe in relation to cardiovascular and psychiatric aspects in a well-selected population. International Journal of Obesity (2009) 33, 857-865; doi: 10.1038/ijo.2009.124; published online 30 June 2009

Massage for Low Back Pain An Updated Systematic Review Within the Framework of the Cochrane Back Review Group

Study Design. Systematic Review. Objectives. To assess the effects of massage therapy for nonspecific low back pain. Summary of Background Data. Low back pain is one of the most common and costly musculoskeletal problems in modern society. Proponents of massage therapy claim it can minimize pain and disability, and speed return to normal function. Methods. We searched MEDLINE, EMBASE, CINAHL from their beginning to May 2008. We also searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, issue 3), HealthSTAR and Dissertation abstracts up to 2006. There were no language restrictions. References in the included studies and in reviews of the literature were screened. The studies had to be randomized or quasi-randomized trials investigating the use of any type of massage (using the hands or a mechanical device) as a treatment for nonspecific low back pain. Two review authors selected the studies, assessed the risk of bias using the criteria recommended by the Cochrane Back Review Group, and extracted the data using standardized forms. Both qualitative and meta-analyses were performed. Results. Thirteen randomized trials were included. Eight had a high risk and 5 had a low risk of bias. One study was published in German and the rest in English. Massage was compared to an inert therapy (sham treatment) in 2 studies that showed that massage was superior for pain and function on both short- and long-term follow-ups. In 8 studies, massage was compared to other active treatments. They showed that massage was similar to exercises, and massage was superior to joint mobilization, relaxation therapy, physical therapy, acupuncture, and self-care education. One study showed that reflexology on the feet had no effect on pain and functioning. The beneficial effects of massage in patients with chronic low back pain lasted at least 1 year after the end of the treatment. Two studies compared 2 different techniques of massage. One concluded that acupuncture massage produces better results than classic (Swedish) massage and another concluded that Thai massage produces similar results to classic (Swedish) massage. Conclusion. Massage might be beneficial for patients with subacute and chronic nonspecific low back pain, especially when combined with exercises and education. The evidence suggests that acupuncture massage is more effective than classic massage, but this need confirmation. More studies are needed to confirm these conclusions, to assess the impact of massage on return-to-work, and to determine cost-effectiveness of massage as an intervention for low back pain.

Immune response to vaccination with DNA-hsp65 in a phase I clinical trial with head and neck cancer patients

DNA-hsp65, a DNA vaccine encoding the 65-kDa heat-shock protein of Mycobacterium leprae (Hsp65) is capable of inducing the reduction of established tumors in mouse models. We conducted a phase I clinical trial of DNA-hsp65 in patients with advanced head and neck carcinoma. In this article, we report on the vaccine`s potential to induce immune responses to Hsp65 and to its human homologue, Hsp60, in these patients. Twenty-one patients with unresectable squamous cell carcinoma of the head and neck received three doses of 150, 400 or 600 mu g naked DNA-hsp65 plasmid by ultrasound-guided intratumoral injection. Vaccination did not increase levels of circulating anti-hsp65 IgG or IgM antibody, or lead to detectable Hsp65-specific cell proliferation or interferon-gamma (IFN-gamma) production by blood mononuclear cells. Frequency of antigen-induced IL-10-producing cells increased after vaccination in 4 of 13 patients analyzed. Five patients showed disease stability or regression following immunization; however, we were unable to detect significant differences between these patients and those with disease progression using these parameters. There was also no increase in antibody or IFN-gamma responses to human Hsp60 in these patients. Our results suggest that although DNA-hsp65 was able to induce some degree of immunostimulation with no evidence of pathological autoimmunity, we were unable to differentiate between patients with different clinical outcomes based on the parameters measured. Future studies should focus on characterizing more reliable correlations between immune response parameters and clinical outcome that may be used as predictors of vaccine success in immunosuppressed individuals. Cancer Gene Therapy (2009) 16, 598-608; doi:10.1038/cgt.2009.9; published online 6 February 2009

Cardiac resynchronization therapy evaluated by myocardial scintigraphy with (99m)Tc-MIBI: changes in left ventricular uptake, dyssynchrony, and function

(99m)Tc-MIBI gated myocardial scintigraphy (GMS) evaluates myocyte integrity and perfusion, left ventricular (LV) dyssynchrony and function. Cardiac resynchronization therapy (CRT) may improve the clinical symptoms of heart failure (HF), but its benefits for LV function are less pronounced. We assessed whether changes in myocardial (99m)Tc-MIBI uptake after CRT are related to improvement in clinical symptoms, LV synchrony and performance, and whether GMS adds information for patient selection for CRT. A group of 30 patients with severe HF were prospectively studied before and 3 months after CRT. Variables analysed were HF functional class, QRS duration, LV ejection fraction (LVEF) by echocardiography, myocardial (99m)Tc-MIBI uptake, LV end-diastolic volume (EDV) and end-systolic volume (ESV), phase analysis LV dyssynchrony indices, and regional motion by GMS. After CRT, patients were divided into two groups according to improvement in LVEF: group 1 (12 patients) with increase in LVEF of 5 or more points, and group 2 (18 patients) without a significant increase. After CRT, both groups showed a significant improvement in HF functional class, reduced QRS width and increased septal wall (99m)Tc-MIBI uptake. Only group 1 showed favourable changes in EDV, ESV, LV dyssynchrony indices, and regional motion. Before CRT, EDV, and ESV were lower in group 1 than in group 2. Anterior and inferior wall (99m)Tc-MIBI uptakes were higher in group 1 than in group 2 (p < 0.05). EDV was the only independent predictor of an increase in LVEF (p=0.01). The optimal EDV cut-off point was 315 ml (sensitivity 89%, specificity 94%). The evaluation of EDV by GMS added information on patient selection for CRT. After CRT, LVEF increase occurred in hearts less dilated and with more normal (99m)Tc-MIBI uptake.

Physiologic parameters that affect pulse transit time difference between the upper and lower limbs in children

Pulse wave velocity (PWV) is a known parameter that is related to arterial distensibility. However, its potential is hampered by the absence of appropriate techniques to estimate it noninvasively. PWV can be used as an assessment of increased arterial stiffness that is linked to systolic hypertension, excess cardiovascular morbidity and mortality.(1,2)

Anemia screening in potential female blood donors: comparison of two different quantitative methods

Anemia screening before blood donation requires an accurate, quick, practical, and easy method with minimal discomfort for the donors. The aim of this study was to compare the accuracy of two quantitative methods of anemia screening: the HemoCue 201(+) (Aktiebolaget Leo Diagnostics) hemoglobin (Hb) and microhematocrit (micro-Hct) tests. Two blood samples of a single fingerstick were obtained from 969 unselected potential female donors to determine the Hb by HemoCue 201(+) and micro-Hct using HemataSTAT II (Separation Technology, Inc.), in alternating order. From each participant, a venous blood sample was drawn and run in an automatic hematology analyzer (ABX Pentra 60, ABX Diagnostics). Considering results of ABX Pentra 60 as true values, the sensitivity and specificity of HemoCue 201(+) and micro-Hct as screening methods were compared, using a venous Hb level of 12.0 g per dL as cutoff for anemia. The sensitivities of the HemoCue 201(+) and HemataSTAT II in detecting anemia were 56 percent (95% confidence interval [CI], 46.1%-65.5%) and 39.5 percent (95% CI, 30.2%-49.3%), respectively (p < 0.001). Analyzing only candidates with a venous Hb level lower than 11.0 g per dL, the deferral rate was 100 percent by HemoCue 201(+) and 77 percent by HemataSTAT II. The specificities of the methods were 93.5 and 93.2 percent, respectively. The HemoCue 201(+) showed greater discriminating power for detecting anemia in prospective blood donors than the micro-Hct method. Both presented equivalent deferral error rates of nonanemic potential donors. Compared to the micro-Hct, HemoCue 201(+) reduces the risk of anemic female donors giving blood, specially for those with lower Hb levels, without increasing the deferral of nonanemic potential donors.

A long-term study in Angora goats experimentally infected with Mycobacterium avium subsp paratuberculosis: Clinical disease, faecal culture and immunological studies

Two longitudinal experiments involving Angora goats challenged with either bovine or ovine strains of Mycobacterium avium subspecies paratuberculosis (Map) have been conducted over a period of 54 and 35 months, respectively. Blood samples for the interferon-gamma (IFN-gamma) test and the absorbed ELISA and faecal samples for bacteriological culture were taken pre-challenge and monthly post-challenge. Persistent shedding, IFN-gamma production, seroconversion and clinical disease occurred earlier with the bovine Map gut mucosal tissue challenge inoculum than with cultured bacteria. The IFN-gamma responses of the gut mucosal tissue and bacterial challenge groups were substantially and consistently higher than those of the control group. The in vivo and cultured cattle strains were much more pathogenic for goats than the sheep strains with persistent faecal shedding, seroconversion and clinical disease occurring in the majority of bovine Map challenged goats. With the ovine Map, 3 goats developed persistent antibody responses but only one of these goats developed persistent faecal shedding and clinical disease. However, there was no significant difference between the IFN-gamma responses of the tissue challenged, bacterial challenged and control groups. Compared with sheep, the ELISA appeared to have higher sensitivity and the IFN-gamma test lower specificity. (C) 2005 Elsevier B.V. All rights reserved.

Quality of diabetes care and coronary heart disease absolute risk in patients with type 2 diabetes mellitus in Australian general practice

Objective: To examine the quality of diabetes care and prevention of cardiovascular disease (CVD) in Australian general practice patients with type 2 diabetes and to investigate its relationship with coronary heart disease absolute risk (CHDAR). Methods: A total of 3286 patient records were extracted from registers of patients with type 2 diabetes held by 16 divisions of general practice (250 practices) across Australia for the year 2002. CHDAR was estimated using the United Kingdom Prospective Diabetes Study algorithm with higher CHDAR set at a 10 year risk of >15%. Multivariate multilevel logistic regression investigated the association between CHDAR and diabetes care. Results: 47.9% of diabetic patient records had glycosylated haemoglobin (HbA1c) >7%, 87.6% had total cholesterol >= 4.0 mmol/l, and 73.8% had blood pressure (BP) >= 130/85 mm Hg. 57.6% of patients were at a higher CHDAR, 76.8% of whom were not on lipid modifying medication and 66.2% were not on antihypertensive medication. After adjusting for clustering at the general practice level and age, lipid modifying medication was negatively related to CHDAR (odds ratio (OR) 0.84) and total cholesterol. Antihypertensive medication was positively related to systolic BP but negatively related to CHDAR (OR 0.88). Referral to ophthalmologists/optometrists and attendance at other health professionals were not related to CHDAR. Conclusions: At the time of the study the diabetes and CVD preventive care in Australian general practice was suboptimal, even after a number of national initiatives. The Australian Pharmaceutical Benefits Scheme (PBS) guidelines need to be modified to improve CVD preventive care in patients with type 2 diabetes.

Age and Method-dependent Variability of Predicted Oxygen Consumption in Congenital Heart Disease

Background and Purpose. There has been a lot of debate about the use of predicted oxygen consumption to calculate pulmonary vascular resistance using the Fick principle. We therefore comparatively analyzed predicted oxygen consumption in infants and children in specific age groups, using different methods (formulas), as an attempt to better understand the usefulness and limitations of predictions. Methods and Results. Four models (LaFarge & Miettinen, Bergstra et al., Lindahl, and Lundell et al.) were used to predict oxygen consumption in 200 acyanotic patients with congenital cardiac defects aged 0-2.0, > 2.0-4.0, > 4.0-6.0, and > 6.0-8.75 years (median 2.04 years). Significant differences were observed between the age groups (P < .001) and between the methods (P < .001), not related to diagnoses. Differences between methods were more impressive in the first age group (P < .01). In patients aged 0-2.0 years, the lowest values of oxygen consumption (corresponding to the highest estimates of pulmonary vascular resistance) were obtained with the method of Lindahl; above this age, any method except that of Lundell et al. Conclusions. Although measuring oxygen consumption is always preferable, a rational use of predictions, using different methods, may be of help in situations where measurements are definitely not possible.

Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

We evaluated the associations between glycemic therapies and prevalence of diabetic peripheral neuropathy (DPN) at baseline among participants in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial on medical and revascularization therapies for coronary artery disease (CAD) and on insulin-sensitizing vs. insulin-providing treatments for diabetes. A total of 2,368 patients with type 2 diabetes and CAD was evaluated. DPN was defined as clinical examination score > 2 using the Michigan Neuropathy Screening Instrument (MNSI). DPN odds ratios across different groups of glycemic therapy were evaluated by multiple logistic regression adjusted for multiple covariates including age, sex, hemoglobin A1c (HbA1c), and diabetes duration. Fifty-one percent of BARI 2D subjects with valid baseline characteristics and MNSI scores had DPN. After adjusting for all variables, use of insulin was significantly associated with DPN (OR = 1.57, 95% CI: 1.15-2.13). Patients on sulfonylurea (SU) or combination of SU/metformin (Met)/thiazolidinediones (TZD) had marginally higher rates of DPN than the Met/TZD group. This cross-sectional study in a cohort of patients with type 2 diabetes and CAD showed association of insulin use with higher DPN prevalence, independent of disease duration, glycemic control, and other characteristics. The causality between a glycemic control strategy and DPN cannot be evaluated in this cross-sectional study, but continued assessment of DPN and randomized therapies in BARI 2D trial may provide further explanations on the development of DPN.

Phase I trial of DNA-hsp65 immunotherapy for advanced squamous cell carcinoma of the head and neck

Considering that mycobacterial heat-shock protein 65 (hsp65) gene transfer can elicit a profound antitumoral effect, this study aimed to establish the safety, maximum-tolerated dose (MTD) and preliminary efficacy of DNA-hsp65 immunotherapy in patients with advanced head and neck squamous cell carcinoma (HNSCC). For this purpose, 21 patients with unresectable and recurrent HNSCC were studied. Each patient received three ultrasound-guided injections at 21-day intervals of: 150, 600 or 400 mu g of DNA-hsp65. Toxicity was graded according to CTCAE directions. Tumor volume was measured before and after treatment using computed tomography scan. The evaluation included tumor mass variation, delayed-type hypersensitivity response and spontaneous peripheral blood mononuclear cell proliferation before and after treatment. The MTD was 400 mg per dose. DNA-hsp65 immunotherapy was well tolerated with moderate pain, edema and infections as the most frequent adverse effects. None of the patients showed clinical or laboratory alterations compatible with autoimmune reactions. Partial response was observed in 4 out of 14 patients who completed treatment, 2 of which are still alive more than 3 years after the completion of the trial. Therefore, DNA-hsp65 immunotherapy is a feasible and safe approach at the dose of 400 mg per injection in patients with HNSCC refractory to standard treatment. Further studies in a larger number of patients are needed to confirm the efficacy of this novel strategy.

An 18-Week, Prospective, Randomized, Double-Blind, Multicenter Study of Amlodipine/Ramipril Combination Versus Amlodipine Monotherapy in the Treatment of Hypertension: The Assessment of Combination Therapy of Amlodipine/Ramipril (ATAR) Study

Background: A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). Objective: The aim of this study was to compare the efficacy and tolerability of an amlodipine/ramipril FDC with those of amlodipine monotherapy. Methods: This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated, based on BP, to 515 then 10/10 mg (amlodipme/ramipril) and 5 then 10 mg (amiodipine). The primary end point was BP measured in the intent-to-treat (ITT) population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema. Results: A total of 222 patients completed the study (age range, 40-79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). The mean (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physician`s office, were significantly greater with combination therapy than monotherapy, with the exception of office DBP (ABPM, -20.76 [1.25] vs -15.80 [1.18] mm Hg and -11.71 [0.78] vs -8.61 [0.74] mm Hg, respectively [both, P = 0.004]; office, -27.51 [1.40] vs -22.84 [1.33] min Hg [P = 0.012] and -16.41 [0.79] vs -14.64 [0.75] mm Hg [P = NS], respectively). In the ITT analysis, the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, -20.21 [1.14] vs -15.31 [1.12] mm Hg and DBP, -11.61 [0.72] vs -8.42 [0.70] mm Hg, respectively [both, P = 0.002]; office: SBP, -26.60 [1.34] vs -22.97 [1.30] mm Hg and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced >= 1 adverse event considered possibly related to study drug. The combmation-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group. Conclusions: In this population of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated. (Clin Ther. 2008;30: 1618-1628) (C) 2008 Excerpta Medica Inc.