Cultural adaptation and validation of the Spanish version of the Cow's Milk-related Symptom Score (CoMiSS) for cow's milk protein allergy.

INTRODUCTION AND AIMS: The prevalence of cow's milk protein allergy in the first year of life varies from 1.8 to 7.5%. The Cow's Milk-related Symptom Score (CoMiSS) was published in 2014 and facilitates the diagnosis of cow's milk protein allergy. It is not meant to replace the clinical diagnosis, but rather to guide the treating team in the diagnostic process and reduce unnecessary diets. The aim was to translate the CoMiSS from English to Spanish and culturally adapt and validate the resulting Spanish version. MATERIALS AND METHODS: An adaptation and validation study on the CoMiSS questionnaire was carried out in two phases: First, the CoMiSS was translated from English to Spanish, after which interrater reliability of the translated score was assessed. Second, interrater reliability tests were carried out on 32 pediatric patients under 7 years of age that were treated for the first time at the Food Allergy Clinic of the Hospital Italiano de Buenos Aires, were suspected of having cow's milk protein allergy, and had not received any treatment, within the time frame of May 2018 and May 2019. RESULTS: Thirty-two patients were evaluated, 14 of whom were females (45%), and the median patient age was 3 months (IQR 2-4). The median result of the first measurement of the scale was 7.0 (IQR 4.5-9.0) and the median of the second measurement was 5.0 (IQR 4.0-8.0). The final intraclass correlation coefficient was 0.80 (95% CI 0.63-0.9). CONCLUSION: The Spanish translation of the CoMiSS was comparable to the original English version, with excellent interrater reliability. This simple and little-known tool has the benefit of being a noninvasive, rapid, reliable, and easy-to-use strategy.

Sleep problems in a sample of children with developmental disorders, before and during the COVID-19 pandemic. / Problemas del sueño en una muestra de niñas y niños con trastornos del desarrollo, antes y durante la pandemia por COVID-19.

INTRODUCTION: Sleep problems (SPs) are common, especially among children with developmental disorders (DDs), and affect their functioning and quality of family life. Pediatricians play a major role in their management. OBJECTIVE: To define the frequency and types of SPs in a sample of children with DDs, determine the proportion of pediatricians who addressed such difficulties, assess the effects of sleep hygiene (SH), and describe the impact of the COVID-19 pandemic on sleep. POPULATION AND METHODS: This was a quasiexperiment. SPs were diagnosed based on parents' concerns and/or clinical criteria. SH strategies were provided and their effect was assessed as per parents' reports and the Children's Sleep Habits Questionnaire in Spanish (CSHQ-S) before and after the strategies. During the COVID-19 pandemic, the SP outcome measure and SH-related outcome measures were measured again. RESULTS: A total of 161 children were included. The frequency of SPs was 55 %; 80 % improved with SH. Eighty-three percent of children had a primary pediatrician; of these, 45 % had consulted about sleep. During the COVID-19 pandemic, SPs increased and SH outcome measures changed. CONCLUSION: Approximately half of children with DDs have SPs; and the problem was only addressed by 45 % of pediatricians. SH was beneficial for most children, so pediatricians' role seems critical. During the COVID-19 pandemic, SPs increased, probably as a result of its environmental impact on children with DDs.

Los problemas del sueño (PS) son frecuentes, principalmente en niñas y niños con trastornos del desarrollo (TD), y causan un impacto en su funcionamiento y calidad de vida familiar. El pediatra tiene un rol importante en su abordaje. Objetivo. Definir la frecuencia y los tipos de PS en una muestra de niñas y niños con TD, determinar la proporción de pediatras que abordaron estas dificultades, evaluar los efectos de la higiene del sueño (HS) y describir el impacto de la pandemia por COVID-19 en el sueño. Población y métodos. Estudio cuasiexperimental. El diagnóstico de PS se realizó con la preocupación de los padres y/o criterios clínicos. Se brindaron estrategias de HS, luego se evaluó su efecto según referencia de los padres y uso del cuestionario CSHQ-S (Children´s Sleep Habits Questionnaire en español) pre- y posestrategias. Durante la pandemia por COVID-19, se midió nuevamente la variable PS y las relacionadas a HS. Resultados. Se incluyeron 161 niñas y niños. La frecuencia de PS fue del 55 %. El 80 % mejoró con HS. El 83 % tenía pediatra de cabecera, y de ellos, el 45 % había preguntado acerca del sueño. Durante la pandemia por COVID-19 hubo aumento de PS y cambios en las variables de HS. Conclusión. Aproximadamente la mitad de los niñas y niños con TD presentan PS; esto solo fue abordado por el 45 % de los pediatras. La HS resultó beneficiosa para la mayoría, por lo que la intervención del pediatra parece fundamental. Durante la pandemia por COVID-19 aumentaron los PS, como posible reflejo del impacto ambiental en los niñas y niños con TD.

Problemas del sueño en una muestra de niñas y niños con trastornos del desarrollo, antes y durante la pandemia por COVID-19 / Sleep problems in a sample of children with developmental disorders, before and during the COVID-19 pandemic

Los problemas del sueño (PS) son frecuentes, principalmente en niñas y niños con trastornos del desarrollo (TD), y causan un impacto en su funcionamiento y calidad de vida familiar. El pediatra tiene un rol importante en su abordaje. Objetivo. Definir la frecuencia y los tipos de PS en una muestra de niñas y niños con TD, determinar la proporción de pediatras que abordaron estas dificultades, evaluar los efectos de la higiene del sueño (HS) y describir el impacto de la pandemia por COVID-19 en el sueño. Población y métodos. Estudio cuasiexperimental. El diagnóstico de PS se realizó con la preocupación de los padres y/o criterios clínicos. Se brindaron estrategias de HS, luego se evaluó su efecto según referencia de los padres y uso del cuestionario CSHQ-S (Children ́s Sleep Habits Questionnaire en español) pre- y posestrategias. Durante la pandemia por COVID-19, se midió nuevamente la variable PS y las relacionadas a HS. Resultados. Se incluyeron 161 niñas y niños. La frecuencia de PS fue del 55 %. El 80 % mejoró con HS. El 83 % tenía pediatra de cabecera, y de ellos, el 45 % había preguntado acerca del sueño. Durante la pandemia por COVID-19 hubo aumento de PS y cambios en las variables de HS. Conclusión. Aproximadamente la mitad de los niñas y niños con TD presentan PS; esto solo fue abordado por el 45 % de los pediatras. La HS resultó beneficiosa para la mayoría, por lo que la intervención del pediatra parece fundamental. Durante la pandemia por COVID-19 aumentaron los PS, como posible reflejo del impacto ambiental en los niñas y niños con TD.

Sleep problems (SPs) are common, especially among children with developmental disorders (DDs), and affect their functioning and quality of family life. Pediatricians play a major role in their management. Objective. To define the frequency and types of SPs in a sample of children with DDs, determine the proportion of pediatricians who addressed such difficulties, assess the effects of sleep hygiene (SH), and describe the impact of the COVID-19 pandemic on sleep. Population and methods. This was a quasi-experiment. SPs were diagnosed based on parents' concerns and/or clinical criteria. SH strategies were provided and their effect was assessed as per parents' reports and the Children's Sleep Habits Questionnaire in Spanish (CSHQ-S) before and after the strategies. During the COVID-19 pandemic, the SP outcome measure and SH-related outcome measures were measured again. Results. A total of 161 children were included. The frequency of SPs was 55 %; 80 % improved with SH. Eighty-three percent of children had a primary pediatrician; of these, 45 % had consulted about sleep. During the COVID-19 pandemic, SPs increased and SH outcome measures changed. Conclusion. Approximately half of children with DDs have SPs; and the problem was only addressed by 45 % of pediatricians. SH was beneficial for most children, so pediatricians' role seems critical. During the COVID-19 pandemic, SPs increased, probably as a result of its environmental impact on children with DD

Secondary hypogammaglobulinemia in Waldmann's disease treated with subcutaneous immunoglobulins.

Primary intestinal lymphangiectasia (PIL) is rare disorder characterized by congenital malformation or obstruction of intestinal lymphatic drainage; it is responsible for protein losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL management. The administration of intravenous immunoglobulins does not always lead to satisfactory plasma levels and therefore the replacement therapy with immunoglobulins is controversial. We describe here the case of a patient with PIL and severe hypogammaglobulinemia treated with immunoglobulins. The striking aspect of this case is the clinical and serological benefit obtained with the subcutaneous compared to the intravenous immunoglobulins administration.

On the fluid dynamics of a laboratory scale single-use stirred bioreactor.

The commercial success of mammalian cell-derived recombinant proteins has fostered an increase in demand for novel single-use bioreactor (SUB) systems that facilitate greater productivity, increased flexibility and reduced costs (Zhang et al., 2010). These systems exhibit fluid flow regimes unlike those encountered in traditional glass/stainless steel bioreactors because of the way in which they are designed. With such disparate hydrodynamic environments between SUBs currently on the market, traditional scale-up approaches applied to stirred tanks should be revised. One such SUB is the Mobius® 3 L CellReady, which consists of an upward-pumping marine scoping impeller. This work represents the first experimental study of the flow within the CellReady using a Particle Image Velocimetry (PIV) approach, combined with a biological study into the impact of these fluid dynamic characteristics on cell culture performance. The PIV study was conducted within the actual vessel, rather than using a purpose-built mimic. PIV measurements conveyed a degree of fluid compartmentalisation resulting from the up-pumping impeller. Both impeller tip speed and fluid working volume had an impact upon the fluid velocities and spatial distribution of turbulence within the vessel. Cell cultures were conducted using the GS-CHO cell-line (Lonza) producing an IgG4 antibody. Disparity in cellular growth and viability throughout the range of operating conditions used (80-350 rpm and 1-2.4 L working volume) was not substantial, although a significant reduction in recombinant protein productivity was found at 350 rpm and 1 L working volume (corresponding to the highest Reynolds number tested in this work). The study shows promise in the use of PIV to improve understanding of the hydrodynamic environment within individual SUBs and allows identification of the critical hydrodynamic parameters under the different flow regimes for compatibility and scalability across the range of bioreactor platforms.

Hemolytic uremic syndrome and rhabdomyolysis in a patient with succinate coenzyme Q reductase (complex II) deficiency.

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Besides diarrhea-associated HUS, due to verotoxin-producing Escherichia coli, in children HUS without prodromal diarrhea may be associated with other infectious and autoimmune diseases, genetic defects of the complement-regulator alternative-pathway, and inborn errors of vitamin B12 metabolism. Rhabdomyolysis is the dissolution of skeletal muscle due to various causes, including inborn errors of metabolism. Recurrent rhabdomyolysis and HUS have been previously described in one patient with a genetic defect of oxidative phosphorylation. We report the case of a 2-year-old boy with recurrent HUS and rhabdomyolysis in whom a succinate coenzyme Q reductase (complex II) deficiency was diagnosed. We hypothesize that defects of oxidative phosphorylation could be another etiological factor in atypical HUS.

Recent changes in bacterial epidemiology and the emergence of fluoroquinolone-resistant Escherichia coli among patients with haematological malignancies: results of a prospective study on 823 patients at a single institution.

BACKGROUND: Regular monitoring of bacterial epidemiology allows evaluation of antibacterial strategies adopted. The aim of this study was to disclose evolving trends in the epidemiology of infections and emerging antibiotic resistance in unselected inpatients with haematological cancers. METHODS: Febrile/infectious episodes occurring in 823 patients consecutively admitted to a single institution during a 16 month period were analysed. Levofloxacin prophylaxis was used in patients with >7 days expected neutropenia. RESULTS: Fever developed in 364 patients (44.2%) and an infection was documented in 187 (22.7%), either clinically (6.1%) or microbiologically (16.6%). Levofloxacin prophylaxis, used in 39.4% of cases, caused a reduction in febrile episodes only among neutropenic patients and no difference in the frequency of documented infections. Among 164 pathogens isolated, gram-negative (49.4%) outweighed gram-positive bacteria (40.9%), Escherichia coli being most frequent (23.2%). Fluoroquinolone resistance and methicillin resistance were the most frequent types of antibiotic resistance, occurring in 56.1% of bacterial isolates and in 66.7% of staphylococci, respectively. Fluoroquinolone-resistant E. coli accounted for 20.1% of all isolates and for 86.8% of E. coli. Multivariate analysis of risk factors for fluoroquinolone resistance identified prophylaxis (P < 0.001) and neutropenia >7 days (P = 0.02) as independent. Methicillin resistance was independently associated with prophylaxis (P = 0.041) and central venous catheters (P = 0.036). Infections by fluoroquinolone-resistant strains did not show a worse outcome. CONCLUSIONS: A shift towards gram-negative bacteria has been occurring in recent years in the bacterial epidemiology of haematological patients. Fluoroquinolone resistance is emerging as a major type of antibacterial resistance, particularly among E. coli strains. Further investigation is needed to explore the consequences of such epidemiological changes.

Quantification of kinetics for enzyme-catalysed reactions: implications for diffusional limitations at the 10 ml scale.

The effects of different reaction scales [100 microl reactions in 96-standard round well (SRW) plates and 10 ml reactions in 24-square well (SW) plates] have been investigated using, as a model, transketolase (TK)-catalysed reaction producing L-erythrulose. Reactions were carried out under non-shaking, shaking and at 10 ml scale stirring conditions to assess the effect of diffusional limitations. Statistical analysis confirmed the significance of the observed difference in reaction rates under given conditions. Only when the laboratory scale system (10 ml) was well mixed did the reaction rate become comparable to that in the microwells, where there is negligible diffusional limitation. These findings have important implications for the scale-up (or scale-down) of enzyme-catalysed reactions.

[How WHI study influences women doctors' behaviour towards menopause]. / Impact de l'étude WHI sur le comportement des femmes médecins vis-à-vis de la ménopause.

OBJECTIVE: A survey entitled FEMME was conducted during 2002 in order to evaluate among French women doctors their own actual or future menopause perception and this before the WHI publication. The results of this American trial possibly modified the perception of these French women doctors. Therefore the same experts group conducted a new survey, from May to September 2003. The main aim of this survey was to evaluate the possible changes in the medical management of the actual or future menopause of these women, and secondarily to evaluate the changes in their patients' behaviour towards hormone replacement therapy (HRT). POPULATION AND METHODS: Postal auto administered questionnaires were sent to the same 10 000 French women doctors (GP or gynaecologist) whatever their menopausal status or their age. 1365 women doctors (respectively 18,5 or 11% of the gynaecologists or GPs contacted) were volunteers to participate in this survey. Among them, 1120 (84,9%) had already participated in the first part of this survey which took place before the WHI publication. RESULTS: 80% of these women doctors have been informed on WHI results principally by professional press or conferences. 70,9% changed their own actual or future menopause perception as follows. No additional selection of non hormonal treatment have been mentioned in comparison with the first part of the survey. On the other hand for HRT, selections of free estrogen plus progestin associations increased whereas those of fixed combinations decreased: this might be linked to the greater variety of estrogen doses, types of progestin and schedules of treatment (mostly with bleeding) offered by this kind of associations. Finally, duration of HRT is included between three and ten years in most cases. DISCUSSION AND CONCLUSION: Thus, unlike most of their patients, these women's physicians always preferred hormonal treatment for their own actual or future menopause. Only the conditions of these treatments have changed.

[Methodology of the inquiry MISSION (menopause, breast cancer risk, morbidity and prevalence)]. / Méthodologie de l'enquête MISSION (Ménopause, rISque de cancer du SeIn, mOrbidité et prévaleNce).

OBJECTIVE: The ambition of this article is to detail and to explain the methodology of the study named MISSION (Menopause: breast cancer risk, morbidity and prevalence). The aims of MISSION are to determine the prevalence of breast cancer and global morbidity in France among menopausal women treated or not with hormone replacement therapy (HRT) and followed by a gynecologist. MATERIAL AND METHOD: 6600 menopausal women [3300 with HRT -- ie for estrogen: only estradiol via oral or transdermal administration; for progestogen: natural progesterone or assimiled or one pregnane derived (excluding medroxyprogesterone acetate) or non-pregnane derived -- and 3300 without HRT] will be enrolled in France between January 5 2004 and February 28 2005 by 825 gynecologists, members or not of the National Federation of Medical Gynecologists (FNCGM). This study design is a historico-prospective with case randomization. MISSION is conducted by a Theramex-Merck Laboratories initiative in collaboration with a WHO (World Health Organization) Collaborating Center for Public Health Aspects of Rheumatic Diseases and a multidisciplinary expert group. CONCLUSION: First results of this study will contribute to better knowledge of women health.

Microscale process evaluation of recombinant biocatalyst libraries: application to Baeyer-Villiger monooxygenase catalysed lactone synthesis.

Microscale processing techniques are rapidly emerging as a cost- effective means for parallel experimentation and hence the evaluation of large libraries of recombinant biocatalysts. In this work, the potential of an automated microscale process is demonstrated in a linked sequence of operations comprising fermentation, enzyme induction and bioconversion using three whole-cell biocatalysts each expressing cyclohexanone monoxygenase (CHMO). The biocatalysts, Escherichia coli TOP 10 [pQR239], E. coli JM107 and Acinetobacter calcoaceticus NCIMB 9871, were first produced in 96-deep square well fermentations at various carbon source concentrations (10 and 20 g L(-1) glycerol). Following induction of CHMO activity biomass concentrations of up to 6 gDCW L(-1) were obtained. Cells from each fermentation were subsequently used for the Baeyer-Villiger oxidation of bicyclo[3.2.0]hept-2-en-6-one, cyclohexanone and cyclopentanone. Each bioconversion was performed at two initial substrate concentrations (0.5 and 1.0 g L(-1)) in order to simultaneously explore both substrate specificity and inhibition. The microscale process sequences yielded quantitative and reproducible data for each biocatalyst on maximum growth rate, biomass yield, initial rate of lactone formation, specific biocatalyst activity and bioconversion yield. E. coli TOP 10 [pQR239] was demonstrated to be an efficient biocatalyst showing substrate specificities and substrate inhibition effects in line with previous studies. Finally, in order to show that the data obtained with E. coli TOP 10 [pQR239] at microwell scale (1,000 microL) could be related to larger scales of operation, the process was performed in a 2-L stirred-tank bioreactor. Using conditions designed to enable microwell kinetic measurements under none oxygen-limited conditions, the fermentation and bioconversion data obtained at the two scales showed good quantitative agreement. This study therefore confirms the potential of automated microscale experimentation for the whole-process evaluation of recombinant biocatalyst libraries and the specification of pilot and process scale operating conditions.

A novel pattern of fast calcium oscillations points to calcium and electrical activity cross-talk in rat chromaffin cells.

Slow oscillations of cytosolic calcium ion concentration - [Ca(2+)](c) - typically originate from release by intracellular stores, but in some cell types can be triggered and sustained by Ca(2+) influx as well. In this study we simultaneously monitored changes in [Ca(2+)](c) and in the electrical activity of the cell membrane by combining indo-1 and patch-clamp measurements in single rat chromaffin cells. By this approach we observed a novel type of spontaneous [Ca(2+)](c) oscillations, much faster than those previously described in these cells. These oscillations are triggered and sustained by complex electrical activity (slow action potentials and spike bursts), require Ca(2+) influx and do not involve release from intracellular stores. The possible physiological implications of this new pathway of intracellular signalling are discussed.

Validation of OSIRIS, a prescreening tool for the identification of women with an increased risk of osteoporosis.

According to the recent recommendations of the European Community and the World Health Organization, identification of risk factors for fracture or low bone mineral density (BMD) should help health professionals to make a better use of bone densitometry. This includes helping patients to modify their behaviour and act on modifiable risk factors (correction of low calcium intake and vitamin D deficiencies, etc.) and also to provide evidence-based guidance for starting a treatment when necessary. In this context, we previously developed a clinical scoring index, OSIRIS (OSteoporosis Index of RISk), for classifying women into three categories of risk of osteoporosis. In order to evaluate the discriminatory performance of OSIRIS, we performed the present prospective study in a sample of 889 postmenopausal women from France. The osteoporosis risk depends on the OSIRIS category. Thus, 62% of women in the 'high-risk' category (OSIRIS < or = -3) were osteoporotic, compared to 34% of women in the 'intermediate-risk' category (OSIRIS ranged between -3 and +1) and only 16.8% of women in the 'low-risk' category (score OSIRIS > 1). These results might contribute to the development of more efficient screening strategies for osteoporosis. The patients in the low-risk category do not require immediate BMD testing; women with 'intermediate risk' have to be carefully followed by their doctor with BMD testing decided on a case-by-case basis; for those within the high-risk category, treatment may be initiated immediately and BMD testing performed either to assess the efficacy of the treatment or to increase the long-term compliance of the patient. In conclusion, for clinical practice, a user-friendly tool has been developed. This tool, called OSIRIS, as far as a simple rule allows, identifies the level of osteoporosis risk in women.

[Comparison of changes in biochemical markers of bone turnover after 6 months of hormone replacement therapy with either transdermal 17 beta-estradiol or equine conjugated estrogen plus nomegestrol acetate]. / Comparaison de l'évolution des marqueurs biologiques du remodelage osseux après six mois de traitement hormonal substitutif par 17 beta-estradiol cutané ou estrogènes sulfoconjugués équins et acétate de nomégestrol.

OBJECTIVE: To compare changes in biochemical markers of bone turnover in postmenopausal women who received sequential discontinuous hormone replacement therapy (HRT) with either transdermal 17 beta-estradiol gel (group 1) or oral equine sulfoconjugated estrogen (group 2), plus nomegestrol acetate. PATIENTS AND METHOD: Prospective, open, randomized, controlled trial, conducted on 3 parallel groups of 106 postmenopausal women. All treated groups received estrogen therapy for 25 consecutive days every month. The estrogen used was either 1.5 mg/day of transdermal 17 beta-estradiol gel (group 1) [N = 42, average age (AA) = 51.6 years, average duration of menopause (ADM = 21.5 months)], or 0.625 mg/day of oral equine sulfoconjugated estrogen (group 2) [N = 39, AA = 51.3 years, ADM = 16.8 months]. In all cases nomegestrol acetate 5 mg/day was added for 12 consecutive days every month. The control group comprised 25 patients, [AA = 53.4 years, ADM = 33.7 months]. Two bone resorption markers: urinary cross-linked N-telopeptide and C-telopeptide of type I collagen (U-NTX/Cr, U-CTX/Cr), and a bone formation marker: serum bone specific alkaline phosphatase activity were measured before and 6 months after treatment start. RESULTS: Significant decreases from baseline values were observed for the 3 biochemical markers in both treated groups compared with control (P < 0.001). There were no significant differences in changes between the 2 treated groups for the 3 biochemical markers. The mean percentage change in the 3 biochemical markers was: from -9.3 to -45.5% in group 1, from -20.5 to -39% in group 2, and from -3.3 to 2% in control group. In group 1, the mean percentage decreases in U-CTX reached optimal threshold of bone turnover change (-45%) which is considered by the International Osteoporosis Foundation as clinically relevant because it predicts an increase in BMD greater than 3% when treatment is maintained over a long term. DISCUSSION AND CONCLUSION: Both treated groups induced a significant comparable decrease of bone turnover markers after 6 months of intervention, compared with control. The group treated with cyclic administration of transdermal 17 beta-estradiol (1.5 mg/day) and nomegestrol acetate (5 mg/day) showed a bone resorption markers decrease corresponding to the threshold of clinical relevance described in the international literature and predictive of positive BMD response in long term.

Prolonged treatment with imatinib mesylate in patients with advanced chronic myeloid leukemia causes a reduction of bcr/abl mRNA levels independent of cytogenetic response.

Bcr/abl mRNA levels were monitored in 13 patients with chronic myeloid leukemia receiving imatinib mesylate over a period of 78 weeks. During treatment median bcr/abl mRNA levels progressively declined from 77.2 normalized dose (nD) at baseline to 11.28 nD after 13 weeks ( P<0.05) and to 1.28 nD after 78 weeks ( P<0.05). After 13 weeks, bcr/abl mRNA levels were significantly lower in cytogenetic responders compared to nonresponders ( P<0.05), but subsequent decrease in the transcript levels caused the loss of any correlation to the cytogenetic status. These results suggest that bcr/abl mRNA levels may reflect cytogenetic response only during the early phases of imatinib therapy.

Development and assessment of the Osteoporosis Index of Risk (OSIRIS) to facilitate selection of women for bone densitometry.

A simple questionnaire would be useful to identify individuals most in need of bone mineral density (BMD) testing. We designed a new predictive model and risk assessment instrument based on an extensive review of the literature evaluating risk factors for osteoporosis, and tested its performance in a large cohort of postmenopausal women in whom BMD was measured by dual x-ray absorptiometry. In total, 1303 postmenopausal women from an outpatient osteoporosis clinic participated in this study. The Osteoporosis Index of Risk (OSIRIS) is based on four variables: age, body weight, current hormone replacement therapy use and history of previous low impact fracture. The sensitivity and specificity for an OSIRIS value of +1 were respectively 78.5% and 51.4%. The AUC under the ROC curve of OSIRIS was 0.71. Three categories were arbitrarily created using OSIRIS, with cutoff of +1 and -3. The low risk category (OSIRIS > +1) represented 41% of all women; only 7% of the women in this category had osteoporosis. The prevalence of osteoporosis was very high (66%) among the group at high risk (OSIRIS < -3 representing 15% of all women). The prevalence of osteoporosis was 39% in the intermediate risk group (-3 < OSIRIS < +1, 44% of all women). In conclusion, OSIRIS is a simple index based on four easy-to-collect variables from postmenopausal women, it shows a high degree of accuracy, and performed well for classifying the degree of risk of osteoporosis in western European women of Caucasian lineage. Based on this instrument it is possible to propose a strategy that would initiate treatment in women with very high risk, postpone BMD measurement in women with low risk and limit BMD measurement to women with intermediate risk of osteoporosis, this would spare more than 55% of the densitometry bill compared with a mass screening scenario.

Influence of daily regimen calcium and vitamin D supplementation on parathyroid hormone secretion.

Calcium and vitamin D supplementation has been shown to reduce secondary hyperparathyroidism and play a role in the management of senile osteoporosis. In order to define the optimal regimen of calcium and vitamin D supplementation to produce the maximal inhibition of parathyroid hormone secretion, we have compared the administration of a similar amount of Ca and vitamin D, either as a single morning dose or split in two doses, taken 6 hours apart. Twelve healthy volunteers were assigned to three investigational procedures, at weekly intervals. After a blank control procedure, when they were not exposed to any drug intake, they received two calcium-vitamin D supplement regimens including either two doses of Orocal D3 (500 mg Ca and 400 IU vitamin D) 6 hours apart or one water-soluble effervescent powder pack of Cacit D3 in a single morning dose (1000 mg Ca and 880 IU vitamin D). During the three procedures (control and the two calcium-vitamin D supplementations), venous blood was drawn every 60 minutes for up to 9 hours, for serum Ca and serum PTH measurements. The order of administration of the two Ca and vitamin D supplementation sequences was allocated by randomization. No significant changes in serum Ca were observed during the study. During the 6 hours following Ca and vitamin D supplementation, a statistically significant decrease in serum PTH was observed with both regimens, compared with baseline and with the control procedure. Over this period of time, no differences were observed between the two treatment regimens. However, between the sixth and the ninth hour, serum PTH levels were still significantly decreased compared with baseline with split dose Orocal D3 administration, while they returned to baseline value with the Cacit D3 preparation. During this period, the percentage decrease in serum PTH compared with baseline was significantly more pronounced with Orocal D3 than with Cacit D3 (P = 0.0021). We therefore conclude that the administration of two doses of 500 mg of calcium and 400 IU of vitamin D3 6 hours apart provides a more prolonged decrease in serum PTH levels than the administration of the same total amount of Ca and vitamin D as a single morning dose in young healthy volunteers. This might have implications in terms of protection of the skeleton against secondary hyperparathyroidism and increased bone resorption and turnover in elderly subjects.

Calcium protects differentiating neuroblastoma cells during 50 Hz electromagnetic radiation.

Despite growing concern about electromagnetic radiation, the interaction between 50- to 60-Hz fields and biological structures remains obscure. Epidemiological studies have failed to prove a significantly correlation between exposure to radiation fields and particular pathologies. We demonstrate that a 50- to 60-Hz magnetic field interacts with cell differentiation through two opposing mechanisms: it antagonizes the shift in cell membrane surface charges that occur during the early phases of differentiation and it modulates hyperpolarizing K channels by increasing intracellular Ca. The simultaneous onset of both mechanisms prevents alterations in cell differentiation. We propose that cells are normally protected against electromagnetic insult. Pathologies may arise, however, if intracellular Ca regulation or K channel activation malfunctions.

Influence of daily calcium and vitamin D supplementation on parathyroid hormone secretion.

Calcium and vitamin D supplementation have been shown to reduce secondary hyperparathyroidism and play a role in age-related osteoporosis. In order to define the optimal regimen of calcium and vitamin D supplementation to produce the maximal inhibition of parathyroid hormone secretion, we compared the administration of a calcium-vitamin D supplement as a single morning dose with the administration of two divided doses at 6-hour intervals. Twelve healthy male volunteers were assigned to three investigational procedures, which were alternated at weekly intervals. After a 'blank' control procedure, when they were not exposed to any supplements, they received one of two calcium-vitamin D supplement regimens: either two doses of Orocal D3 (500 mg calcium and 400 IU vitamin D3) with a 6-hour interval between doses, or one water-soluble effervescent powder pack of Cacit vitamin D3, taken in the morning (1000 mg calcium and 880 IU vitamin D3). During the three procedures (control and the two calcium-vitamin D supplementation protocols), veinous blood was drawn every 60 minutes for up to 9 hours, for serum calcium and parathyroid hormone measurements. The order of administration of the two calcium and vitamin D supplementation regimens was allocated by randomization. No significant changes in serum calcium were observed during the study. During the first 6 hours following calcium-vitamin D supplementation, a statistically significant decrease in serum parathyroid hormone was observed with both regimens, compared with baseline and the control procedure. During this first period, no differences were observed between the two treatment regimens. However, between the 6th and the 9th hour, serum parathyroid hormone levels remained significantly decreased compared to baseline with the twice-daily Orocal D3 administration, while they returned to baseline values with the once-daily Cacit D3 preparation. During this period, the percentage decrease in serum parathyroid hormone relative to baseline was significantly greater with Orocal D3 than Cacit D3 (p = 0.0021). We therefore conclude that the twice-daily administration of 500 mg calcium and 400 IU vitamin D3 at 6-hour intervals provides a more prolonged decrease in serum parathyroid hormone levels than the administration of the same total amount of calcium and vitamin D, as a single morning dose in young healthy.

[Determination of acceptability of 2 cutaneous estradiol gels, in a dose of 1.5 mg daily]. / Appréciation de l'acceptabilité de deux gels d'estradiol cutané, à la dose d'1,5 mg par jour.

OBJECTIVE: The aim was to compare acceptability of a percutaneous 0. 1% estradiol gel (Gel A, Estreva(R) Gel, Laboratoire Théramex, Monaco) to that of an 0.06% estradiol gel (Gel B, Oestrodose(R), Laboratoires Besins-Iscovesco) in its new formulation and packaging. MATERIAL AND METHODS: This randomized, crossed, simple-blind study was carried out in 48 volunteer healthy postmenopausal women. The volunteers applied on one forearm 1.5 mg/day of cutaneous estradiol in the form of either gel, according to randomized allocation, for four days without free period between the two therapeutic periods. The application and drying times of the two gels were measured during the first application; gel subjective women assessment was collected at the beginning and at the end of the study. RESULTS: Mean application and drying times with Gel A are significantly reduced, compared to Gel B (p=0.0259 and p=0.0001, respectively) with drying time 61% shorter; these data are confirmed by subjective women evaluation. The two gels are not significantly different regarding several criteria as consistency, ease of application and sensation of lasting stickiness. However, a significant difference is found in favour of Gel A on the following items: practicality of application (p=0.007), ease of penetration (p<0.001), quantity of gel to apply (p<0.001) after the first application. After four days of administration, a same significant difference is observed concerning practicality of the gel (p=0.0078), duration of use (p<0. 001), packaging, women opinion on the gel (p=0.022) and the product, gel and packaging (p<0.001). At the end of the study, gel A utilization is considered by women more practical (p=0.001) with an easier application (p<0.001) and less restricting while applying (p=0.001), compared to Gel B; 72.9% of women prefer the Gel A and 12. 5% of women prefer the Gel B. CONCLUSION: A better acceptability of the 0.1% estradiol gel and of its packaging compared to that of the 0.06% estradiol gel in this new formulation and packaging is observed in this study.