Nasal chemosensory tests: biomarker between dementia with Lewy bodies and Parkinson disease dementia.

BACKGROUND: Dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) are progressive and disabling neurodegenerative disorders, which are often misdiagnosed due to theirs overlapping clinical and paraclinical features. Nevertheless, their adequate management requires an accurate differential diagnosis. The main aim of this study was to investigate the usefulness of olfactory and trigeminal nasal testing for the differential diagnosis between DLB and PDD. METHODS: Odor thresholds to three odorants differentially activating the olfactory and trigeminal systems were assessed in patients with DLB, PDD and healthy controls (n = 20 per group). RESULTS: Odor thresholds were significantly different between the three groups of subjects. More precisely, we found that DLB patients had significantly lower detection threshold performances compared to PDD patients. Moreover, using a standard canonical discriminant analysis, we confirmed a plain differentiation between the three groups. CONCLUSIONS: The current study highlights that DLB patients have very poor olfactory and trigeminal detection threshold performances, which are significantly lower, compared to PDD patients. These results suggest that olfactory testing, using odorants that stimulate both the olfactory and trigeminal systems, could constitute an interesting biomarker and contribute to the differential diagnosis of PDD and DLB patients. Further researches, notably on olfacto-trigeminal interactions, are warranted in these populations to support our findings.

Parkinson disease in eldery patients: lessons from odour detection thresholds on olfacto-trigeminal interaction.

BACKGROUND: Human nasal chemosensation is mediated by two separate, though interacting sensory pathways: the trigeminal and olfactory systems. Trigeminal sensitivity and olfacto-trigeminal interactions have not yet been well studied in idiopathic Parkinsons disease (IPD). OBJECTIVES: The aim of this study was to assess odour detection thresholds in elderly IPD patients, and compare them to the odour detection thresholds of healthy controls. Finally, we investigated potential interactions between trigeminal and olfactory sensitivity. METHODS: 89 IPD patients aged over 65 and 89 matched healthy participants were enrolled in the study. Odour detection thresholds to 3 stimuli differentially activating olfactory and trigeminal afferents (Phenyl-ethyl alcohol, n-Butanol and Pyridine) were assessed, using an ascending staircase, binary forced-choice procedure. RESULTS AND CONCLUSION: Detection threshold scores were able to discriminate between elderly IPD and controls. Pyridine was less effective than the two other odorants, suggesting that trigeminal pathway is less impaired than the olfactory system. We found that the detection thresholds were significantly different between IPD patients with good autonomy, and patients with impaired autonomy.

Body mass index and childhood obesity classification systems: A comparison of the French, International Obesity Task Force (IOTF) and World Health Organization (WHO) references.

AIM: This study aims to compare three body mass index (BMI)-based classification systems of childhood obesity: the French, the International Obesity Task Force (IOTF) and the World Health Organization (WHO) references. METHODS: The study involved 1382 schoolchildren, recruited from the Lille Academic District in France in May 2009 aged 8.4±1.7 years (4.0-12.0 years). Their mean height and body mass were 131.5±10.9cm and 30.7±9.2kg, respectively, resulting in a BMI of 17.4±3.2kg/m(2). The weight status was defined according to the three systems considered in this study. The agreement between these references was tested using the Cohen's kappa coefficient. RESULTS: The prevalence of overweight was higher with the WHO references (20.0%) in comparison with the French references (13.8%; P<0.0001) and the IOTF (16.2%; P≤0.01). A similar result was found with obesity (WHO: 11.6% vs. IOTF: 6.7%; or French references: 6.7%; P<0.0001). Agreement between the three references ranged from "moderate" to "perfect" (0.43≤κ≤1.00; P<0.0001). Kappa coefficients were higher when the three references were used to classify children as obese (0.63≤κ≤1.00; P<0.0001) as compared to classification in the overweight (obesity excluded) category (0.43≤κ≤0.94; P<0.0001). When sex and age categories (4-6 years vs. 7-12 years) were considered to define the overweight status, the lowest kappa coefficient was found between the French and WHO references in boys aged 7-12 years (κ=0.28; P<0.0001), and the highest one in girls aged 7-12 years between the French references and IOTF (κ=0.97; P<0.0001). As for obesity, agreement between the three references ranged from 0.60 to 1.00 (P<0.0001), with the lowest values obtained in the comparison of the WHO references against French references or IOTF among boys aged 7-12 years (κ=0.60; P<0.0001). CONCLUSION: Overall, the WHO references yield an overestimation in overweight and/or obesity within this sample of schoolchildren as compared to the French references and the IOTF. The magnitude of agreement coefficients between the three references depends on of both sex and age categories. The French references seem to be in rather close agreement with the IOTF in defining overweight, especially in 7-12-year-old children.

Does the body adiposity index (BAI) apply to paediatric populations?

OBJECTIVE: Validation of body adiposity index (BAI) in a paediatrics sample; and to develop, if necessary, a valid BAI for paediatrics (i.e. BAIp). METHODS: A total of 1615 children (52% boys) aged 5-12 years underwent anthropometry. Their body composition was assessed using a foot-to-foot bioimpedance. The validity of BAI = (Hip circumference/Height(1.5)) - 18 was tested by combining correlation and agreement statistics. Then, the sample was split into two sub-samples for the construction of BAIp. A regression was used to compute the prediction equation for BAIp-based percentage of body fat (%BF). RESULTS: The initial BAI over-estimated the %BF of children by 49% (29.6 ± 4.2% versus 19.8 ± 6.8%; p < 0.0001). The original methodology led to a BAIp = (Hip circumference/Height(0.8)) - 38 in children. When compared to BAI, BAIp showed both better correlation (r = 0.57; p < 0.01 versus r = 0.74; p < 0.0001) and agreement (ICC = 0.34; [95% CI = -0.19-0.65] versus ICC = 0.83; [95% CI = 0.81-0.84]). However, there were some systematic biases between the two values of %BF as exemplified by the large 95% limit of agreement [-9.1%; 8.8%] obtained. CONCLUSION: BAI over-estimates the %BF in children. In contrast, BAIp appears as a new index for children's body fatness, with acceptable accuracy. In its current form, this index is valid only for large-scale studies.

Does biological maturity actually confound gender-related differences in physical activity in preadolescence?

AIM: To examine: (i) if maturity-related gender differences in moderate-to-vigorous physical activity (MVPA) depend on how maturity status is defined and measured; and (ii) the influence of maturity level on compliance with PA recommendations. METHODS: The study involved 253 children (139 boys) aged 9.9 ± 0.9 years, with mean stature and weight of 1.39 ± 0.08 m and 35.8 ± 8.8 kg respectively. Their PA was evaluated using an Actigraph accelerometer (Model 7164). Maturity was assessed using the estimated age at peak height velocity (APHV) and a standardized APHV by gender (i.e. centred APHV). RESULTS: Boys engaged in significantly more MVPA than girls (P < 0.0001). There was a significant correlation between the centred APHV and MVPA in boys (r = 0.20; P = 0.016), but not in girls (r = 0.13; P = 0.155). An ancova controlling for the estimated APHV showed no significant interactions between gender and APHV, and the main effect of gender on MVPA was negated. Conversely, there was a significant main effect of APHV on MVPA (F 1,249 = 6.12; P = 0.014; η p (2) = 0.024). Only 9.1% of children met the PA recommendations, including 14.4% of boys and 2.6% of girls (P < 0.01). This observation also applies in both pre-APHV (12.7% of boys vs. 2.4% of girls, P < 0.001) and post-APHV children (23.8% of boys vs. 3.4% of girls, P < 0.0001). No differences in PA guidelines were observed between pre-APHV and post-APHV children. CONCLUSIONS: Among prepubescent children, the influence of biological maturity on gender differences in PA may be a function of how maturity status is determined. The most physically active prepubescent children were those who were on time according to APHV.

Mathematical and physical model of gravity-fed infusion outflow: application to soft-bag-packed solutions.

Gravity-fed infusion (GFI) systems are acknowledged as being unable to keep their flow-rate constant. This may affect drug plasma levels such as aminoglycosides. Numerous factors have previously been cited, but their relative importance has never been quantified so far. The objective of this work is to identify the main factors that influence GFI in vitro outflow and to propose a mathematical model of flow-rate evolution as a function of time. In this model, pressure loss and infusion device creep have been considered as the main variation factors. Concomitantly, two experiments were undertaken. Firstly, the flow-rate evolution of an in vitro infusion of 250 mL of dextrose 5% was assessed. Secondly, the creep occurring on an infusion device was measured through a stress relaxation experiment. The experimental infusion flow-rate decreased by as much as 28.5% over 1 h. Simulated and experimental data are well correlated (r = 0.987; P < 0.0001). The maximum creep effect happens during the first 15 min of infusion. In this work, height of the liquid in the bag and tube creep were found to be the main variation factors in GFI flow-rate. This new mathematical model should help to explain the differences observed in drug plasma levels with gravity-fed devices.

Irisin levels in LMNA-associated partial lipodystrophies.

AIM: The adipo-myokine irisin regulates energy expenditure and fat metabolism. LMNA-associated familial partial lipodystrophy (FPLD2) comprises insulin resistance, muscle hypertrophy and lipoatrophy. The aim of this study was to investigate whether irisin could be a biomarker of FPLD2. PATIENTS AND METHODS: This case control study included 19 FPLD2 subjects, 13 obese non-diabetic (OND) patients and 19 healthy controls (HC) of normal weight (median BMI: 26, 39 and 22 kg/m2, respectively). Serum irisin and leptin levels, body composition (DXA/MRI) and metabolic/inflammatory parameters were compared in these three groups. RESULTS: BMI and MRI intra-abdominal fat significantly differed among these three groups, whereas DXA total fat mass and leptin levels were higher in the OND group, but did not differ between HC and FPLD2. Lipodystrophy patients had higher intra-abdominal/total abdominal fat ratios than the other two groups. Irisin levels were higher in FPLD2 and OND patients than in HC (medians: 944, 934 and 804 ng/mL, respectively). However, irisin/leptin ratios and lean body mass percentages were strikingly higher, and lean mass indices lower, in FPLD2 and HC than in the OND (median irisin/leptin ratios: 137, 166 and 21, respectively). In the entire study group, irisin levels positively correlated with BMI, lean body mass and index, intra-abdominal/total abdominal fat ratio, triglyceride, cholesterol, insulin, glucose and HbA1c levels. Also, intra-abdominal/total abdominal fat ratio and lean body mass better differentiated the three groups only in female patients. CONCLUSION: Circulating irisin is similarly increased in FPLD2 and OND patients, who are characterized by higher lean body mass regardless of their clearly different fat mass. However, irisin/leptin ratios, strikingly higher in FPLD2 than in OND patients, could help to make the diagnosis and prompt genetic testing in clinically atypical cases.

[Nephelometry or turbidimetry for the determination of albumin, ApoA, CRP, haptoglobin, IgM and transthyretin: which choice?]. / Turbidimétrie ou néphélémétrie: quel choix pour les dosages de l'albumine, l'ApoA, la CRP, l'haptoglobine, l'IgM et la transthyrétine?

Nephelometry, which is considered as the reference method for serum proteins determination requires a specific equipment. The majority of protein determinations are therefore carried out on biochemistry automats using turbidimetry. The objective of a CNBH group (Collège national de biochimie des hôpitaux) was to compare nephelometry and turbidimetry for 7 automats: 2 nephelometers, the BN Prospec (Dade-Behring) and Immage (Beckman-Coulter) and 5 biochemistry systems using turbidimetry, the Integra and Modular (Roche Diagnostics), the LX20 (Beckman-Coulter), RXL (Dade-Behring) and AU (Olympus). The study was based on the determination of sera collections (albumin, ApoA, CRP, haptoglobin, IgM, transthyretin) of 140 samples each: 110 limpid samples and 30 samples called HLI (hemolytic, lipemic or icteric). Fifteen hospitals took part to this work. An ANOVA analysis on limpid samples and quality control sera concluded to an "automat" effect for the 6 tested proteins but did not show a "method" effect, (i.e. nephelometry versus turbidimetry). On the other hand, the transferability of the results was expected to be better and an effort on the choice of the antibodies and the standardization procedures should be made.

An architecture for online comparison and validation of processing methods and computerized guidelines in intensive care units.

Clinical decision support systems are a combination of software techniques to help the clinicians in their medical decision making process via functionalities ranging from basic signal analysis to therapeutic planning and computerized guidelines. The algorithms providing all these functionalities must be very carefully validated on real patient data and must be confronted to everyday clinical practice. One of the main problems when developing these techniques is the difficulty to obtain high-quality complete patient records, comprising data coming both from the biomedical equipment (high-frequency signals), and from numerous other sources (therapeutics, imagery, clinical actions, etc.). In this paper, we present an infrastructure for developing and testing such software algorithms. It is based on a bedside workstation where testing different algorithms simultaneously on real-time data is possible in the ward. It is completed by a collaborative portal enabling different teams to test their software algorithms on the same patient records, making comparisons and cross-validations more easily.

Tests for genetic linkage and homogeneity.

This report concerns likelihood ratio tests in a heterogeneous model for linkage, where the recombination fraction has a binomial mixture distribution with an unknown proportion of unlinked families. We consider families of unequal sizes with known or unknown phase data. In both cases, the limit distributions of the linkage test statistics are a mixture of a mass at ) and of a X2/1 distribution in equal proportions and homogeneity test statistics tend to the supremum of Gaussian processes. The critical values of the homogeneity tests are simulated, and the power functions of the linkage and homogeneity tests are compared in a simulation study.

An extension of the admixture test for the study of genetic heterogeneity in hereditary multiple exostoses.

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the presence of multiple cartilage-capped exostoses in the juxta-epiphyseal regions of the long bones. EXT is heterogeneous with at least three different locations currently having been identified on chromosomes 8, 11 and 19. We have tested a series of 29 EXT families for possible linkage to the three disease loci and estimated the probability of linkage of the disease to each locus in our series, by using an extension of the admixture test, which makes modelling of heterogeneous monogenic disease feasible. The maximum likelihood was obtained for proportions of 44%, 28% and 28% of families being linked to chromosome 8, 11 and 19, respectively. The a posteriori probability of linkage of the disease to EXT1, EXT2 and EXT3 was greater than 80% for 8/29, 5/29 and 3/29 families, respectively, and did not give evidence of a fourth locus for the disease. The present approach can be generalized to the investigation of genetic heterogeneity in other monogenic diseases, as it simultaneously estimates the location of each disease gene and the proportion of families linked to each locus.