Acceptability of 12 fortified balanced energy protein supplements ‐ Insights from Burkina Faso

Poor maternal nutrition contributes to poor birth outcomes, including low birth weight and small for gestational age births. Fortified balanced energy protein (BEP) supplements may be beneficial, although evidence is limited. This mixed method study, conducted among pregnant women in Burkina Faso, is part of a larger clinical trial that seeks to understand the impact of fortified BEP supplements on pregnancy outcomes and child growth. The formative research reported here, a single‐meal rapid assessment of 12 product formulations, sought to understand product preferences for provision of BEP supplements and contextual factors that might affect product acceptability and use. Results indicate a preference for products perceived as sweet rather than salty/savoury and for products perceived as familiar, as well as a sensitivity to product odours. Women expressed a willingness and intention to use the products even if they did not like them, because of the health benefits for their babies. Data also indicate that household food sharing practices may impact supplement use, although most women denied any intention to share the products. Sharing behaviour should therefore be monitored, and strategies to avoid sharing should be developed during the succeeding parts of the research.     

Stentless and stented aortic valve replacement in elderly patients: Factors affecting midterm clinical and hemodynamical outcome.

OBJECTIVE: To report on the midterm results of aortic valve replacement (AVR) with stented and stentless bioprosthesis in an elderly population by analyzing the factors affecting survival and hemodynamical performance. METHODS: In a retrospective study, 145 patients with a Toronto stentless prosthesis are compared with 110 patients with a stented Carpentier-Edwards valve. The 5- to 10-year clinical outcome, transprosthetic gradients, and early and late left ventricular mass (LVM) regression are analyzed in view of specific prosthesis- and patient-related factors. RESULTS: Actuarial survival at 5 years is 82% after stentless AVR versus 68% after stented AVR (p < 0.001) in elderly patients. However, there was no difference in survival at 8 years, being 55.9% and 59.5%, respectively. Univariate analysis revealed that advanced age at the time of operation, NYHA class IV, use of a stented xenograft, presence of patient-prosthesis mismatch (PPM) (IEOA < or = 0.85 cm2/m2), and severe preoperative left ventricular (LV) hypertrophy (LVMI > 180 g/m2) affected survival adversely. But multivariate analysis determined only age, NYHA class IV and excessive LV hypertrophy as independent predictors of late mortality. Stented and stentless xenografts were equally effective in terms of transprosthetic gradients and LVMI regression. The use of a stentless valve significantly reduced the occurrence of PPM (18% vs 41%, p < 0.01). Early LVMI regression at 1 year was optimized by the avoidance of PPM, indicated by a higher absolute (43.7+/-28.3 g/m2 vs 58.6+/-33.8 g/m2, p = 0.003) and relative (25.0+/-12.7% vs 31.4+/-14.9%, p=0.004) mass regression. However, late LV remodeling was predominantly affected by systemic hypertension and severe preoperative LV hypertrophy, resulting in the incomplete LVMI resolution in 61.3% and 66.7% of these patients, respectively. Conclusion: In elderly patients, aortic valve replacement appears to be equally effective with a stentless or stented bioprosthesis. Midterm clinical outcome is mainly determined by patient-related factors such as age, advanced NYHA class, and severity of preoperative LV hypertrophy. Regarding post-AVR left ventricular remodeling, patient-prosthesis mismatch influences the early phase, whereas arterial hypertension affects the late regression more. However, the left ventricular remodeling is continuously compromised by the preoperative presence of excessive hypertrophy, despite the efficacy of the aortic valve replacement.     

Characterization of the extracellular serotonin release in the substantia nigra of the freely moving rat using microdialysis

The characteristics of the serotonin release were investigated in the substantia nigra (SN) of the freely moving rat using microdialysis. We also examined whether the delay between surgery and microdialysis experiments might influence these characteristics by implanting rats with a guide cannula 1 or 2 days prior to microdialysis experiments. In the first group, the tissue was not punctured until the microdialysis probe was inserted the evening before the experiment. In the second group, the nigral tissue was punctured with an extended obturator which was then replaced by a microdialysis probe the evening before the experiment. After administration of 60 mM K⁺ a more pronounced increase in serotonin was observed in the first group (260%) compared to the second group (159%). Calcium-free and tetrodotoxin (TTX, a sodium channel blocker) (1 μM) perfusion reduced extracellular serotonin to respectively 77% and 80% in the first group and 70% and 64% in the second group. These results suggest that vesicular release of nigral serotonin only occurs partially in this region and that minimizing the damage caused by implantation of the probe results only in 10% more vesicular release of serotonin. However, blockade of the serotonin reuptake carrier caused more TTX sensitivity of the serotonin release. Also, stimulation of the dorsal raphe by locally perfusing 60 mM K⁺ decreased serotonin in the SN, confirming the anatomical and functional link between both areas.     

Evaluation of new commercial enzyme-linked immunosorbent assay kits in the laboratory diagnosis of antiphospholipid syndrome in view of the revised classification criteria of the antiphospholipid syndrome.

Amendments to the Sapporo criteria for the diagnosis of the antiphospholipid syndrome (APS) have recently be published and include testing for the presence of IgG and IgM beta2-glycoprotein I (beta(2)GPI) antibodies. The Asserachrom Antiphospholipid antibodies line (Diagnostica Stago) with a monoclonal based standardisation, was evaluated in a Lupus anticoagulant (LAC) positive (n = 138) and a LAC negative (n = 134) populations. The ELISA line consists of the Asserachrom APA Screen, the Asserachrom APA IgG,M and the Asserachrom anti-beta(2)GPI IgG and IgM. Anti-prothrombin antibodies (APT), not being included in the updated laboratory criteria, have been tested by the Asserachrom anti-prothrombin IgG,M. Imprecision characteristics showed coefficients of variation (CV) ranging from 4.9% to 13.9%. Cut-off values were calculated with the 99 percentile. The Asserachrom APA Screen showed 1,5% false positive and 0,7% false negative results in correlation with the Asserachrom APA IgG,M. 14.7% of the patients were positive for beta2GPI antibodies, 30,0% of them showed a negative Asserachrom APA Screen. beta(2)GPI antibodies may be the only test positive in a minority of patients, so the Asserachrom APA Screen and the Asserachrom anti-beta(2)GPI IgG and IgM should be performed in parallel when APS is suspected. LAC and APA assays, however, remain essential in the laboratory diagnosis of APS.     

Differential effects of restraint stress on hippocampal 5-HT metabolism and extracellular levels of 5-HT in streptozotocin-diabetic rats

Streptozotocin (STZ)-elicited diabetes reduces central serotonin (5-hydroxytryptamine, 5-HT) synthesis/metabolism, but whether this reduction leads to decreased release of 5-HT has only scarcely been investigated. We have thus analysed the impact of STZ diabetes on hippocampal extracellular 5-HT levels both under basal conditions and during restraint stress, a procedure known to stimulate hippocampal 5-HT synthesis/metabolism and release. The pretreatment with STZ (3 weeks beforehand) and the 1 h restraint session respectively decreased and increased hippocampal 5-HT metabolism, as assessed by tissue analysis of 5-HT and 5-hydroxyindoleacetic acid. On the other hand, hippocampal microdialysis revealed no difference in basal levels of extracellular 5-HT levels in (conscious) vehicle- and STZ-pretreated rats, but a differential effect of restraint. Thus, extracellular 5-HT levels increased throughout restraint (maximal increase: 194%) in vehicle-, but not in STZ-pretreated rats. In the latter rat group, plasma corticosterone levels were, however, increased, thus indicating a significant aversiveness to stress. Lastly, because anxiety-related behaviours may be affected by hippocampal serotonergic systems, resting and restrained vehicle- and STZ-pretreated rats were compared (immediately after stress) in an elevated plus-maze of anxiety. Pretreatment with STZ reduced the percent number of open arm entries and the number of closed arm entries, indicating increased anxiety and reduced locomotor activity, respectively. Restraint tended to increase anxiety-related behaviours in all rats, but this trend never reached significance. Our results confirm that gross analyses of 5-HT metabolism do not yield information on 5-HT release, and suggest that the prevalence of diabetes among patients suffering affective disorders could be related to the lack of hippocampal serotonergic response to aversive stimuli.     

Final results of a Phase I/II dose escalation trial in non-small-cell lung cancer using three-dimensional conformal radiotherapy

PURPOSE: The aim of this study was to determine the maximum tolerated dose (MTD) delivered within 6 weeks in patients with non-small-cell lung cancer (NSCLC). The impact of tumor volume and delivered dose on failure-free interval (FFI) and overall survival (OS) were also studied. METHODS AND MATERIALS: A Phase I/II trial was performed including inoperable NSCLC patients. According to the relative mean lung dose (rMLD), five risk groups with different starting doses were defined: Group 1, rMLD 0.0 to 0.12; Group 2, rMLD 0.12 to 0.18; Group 3, rMLD 0.18 to 0.24; Group 4, rMLD 0.24 to 0.31; and Group 5, rMLD 0.31 to 0.40. Patients underwent irradiation with 2.25 Gy per fraction and a fixed overall treatment time of 6 weeks. The dose was escalated with 6.75 Gy after 6 months follow-up without dose-limiting toxicity. If more than 30 fractions were prescribed, twice-daily irradiation was performed with at least a 6-h interval. RESULTS: A total of 88 patients were included. Tumor Stage I or II was found in 53%, IIIA in 31%, and IIIB in 17%. The MTD was not achieved in risk Group 1 (reached dose, 94.5 Gy). For risk Groups 2 and 3 the MTD was 81 Gy. The 74.3-Gy dose was determined to be safe for Group 4 and the 60.8-Gy dose for Group 5. In 2 patients (5%) an isolated nodal relapse occurred. Based on multivariable analysis, higher doses significantly increased the FFI (p = 0.02) for the total group. The OS was increased in the lower risk groups (p = 0.05) but not in the higher risk groups (p = 0.4). CONCLUSION: Dose escalation is safe up to 94.5 Gy in 42 fractions in 6 weeks in patients with an MLD 13.6 Gy or less. Higher doses are associated with a better FFI and OS for smaller tumor volumes. Involved-field irradiation results in a low percentage of isolated nodal relapses.     

Prospective clinical evaluation of lower cut-offs for galactomannan detection in adult neutropenic cancer patients and haematological stem cell transplant recipients

The recent advent of an improved commercial serum enzyme-linked immunosorbent assay (ELISA) for the detection of circulating galactomannan (GM), a major constituent of Aspergillus cell walls, has contributed to the diagnosis of invasive aspergillosis (IA) in many haematology and transplant centres. However, the optimal threshold for positivity remains a matter of debate. We prospectively evaluated the impact of lowering the cut-off in 124 neutropenic episodes with a high pretest probability for IA. Two new cut-off points, lower than previously accepted, are proposed: (a) a 'static' cut-off at 0.8 and (b) a 'dynamic' cut-off at 0.5. A single assay with an optical density (OD) index > or = 0.8 warrants the initiation of anti-Aspergillus therapy. A further lowering of the 'static' threshold seems not clinically feasible given the drop in positive predictive value (PPV). However, the demonstration of at least two sequential sera with an OD > or = 0.5 ('dynamic' threshold) increased the specificity and the PPV to 98.6% and the efficiency to 98%. Applying both cut-offs to a subgroup of 21 'possible' fungal infections further identified and upgraded six cases of IA. However, the clinical benefit of lower cut-offs (particularly for earlier diagnosis) depends upon the kinetics of antigenaemia and the intensity of serum sampling.