Inhibition of CD203c membrane up-regulation in human basophils by high dilutions of histamine: a controlled replication study

none5noPrevious research suggests that human basophil activation may be inhibited by histamine even at extremely low doses (high dilutions). In our experiment, membrane up-regulation of CD203c, which proved to be a more consistent activation marker than CD63, was significantly inhibited in samples treated with histamine at the dilutions of 2C, 12C, 14C, 15C and 16C. Control water dilutions/succussions did not show any significant effect. Therefore, using a strictly standardized flow cytometry protocol and a new dilution/succussion procedure, we have shown that low and high dilution of histamine do inhibit CD203c up-regulation in anti-IgE stimulated basophils.mixedS. Chirumbolo; M. Brizzi; R. Ortolani; A. Vella; P. BellaviteS. Chirumbolo; M. Brizzi; R. Ortolani; A. Vella; P. Bellavit

The basophil activation test confirms cow's milk allergy in non-sensitised children with allergy symptoms

International audienceBackground: The need for an oral food challenge (OFC) surrogate is growing in line with the continuous increase in the prevalence and severity of pediatric food allergy. The basophil activation test (BAT) is currently used for the diagnosis of venom and drug allergies. We made the hypothesis that BAT might improve the sensitivity of cow's milk (CM) allergy diagnosis in pediatric patients with negative skin prick tests (NSPT) and undetectable specific serum immunoglobulin E (USSIgE). Methods: BAT with CM extract (BAG-F2, Flow and Flow2CAST, Buhlmann Labs, Switzerland, final concentrations 25, 12.5, 5 and 1 ng/mL) was performed on freshly drawn blood from 50 consecutive CM allergic patients (0.5-14 years) with NSPT, USSIgE and positive CM oral challenge. For each donor, 3 controls were assessed: negative control (reaction buffer), positive controls (anti-IgE receptor and fMLP). BAT specificity was assessed with clinically irrelevant allergens in the study group and with CM extract BAG-F2 in non-allergic donors. BAT was monitored through flow cytometric membrane variations of CD63 expression and CCR3 downregulation. The percentage of CD63+ basophils and the mean fluorescence intensity of CD63 and CCR3 were used to define the basophil stimulation index. BAT was considered positive if at least 2 consecutive concentrations of CM extract induced a stimulation index of 2 or more compared with the negative control. Results: Cow's milk BAT was positive in 33 children and negative in 15. Two patients' results were not included in the final statistical analysis (one IgE-receptor non-responder and one rejection for technical reasons). BAT to irrelevant allergens in patients, as well as BAT to CM extract in nonallergic controls, were negative in 27 cases but positive for 3 BAT to CM in CM-tolerant children. BAT was subsequently used for the follow-up of 5 positive children, two of them over a period of 4 years, with results closely matching those of the oral food challenge. Conclusion: BAT brought the biological proof of food allergy in 33 out of 50 CM allergic children with NSPT and USSIgE. The sensitivity of the test was 69%, with 90% specificity, 90% positive predictive value and 64% negative predictive value. Clinical relevance: Cow's milk BAT proved to be a useful tool for the diagnosis and follow-up of CM allergy in children with NSPT and USSIgE. A positive CM BAT in such patients might therefore avoid OFC, but a negative test still needs OFC confirmation

Rehabilitation of 190 non-ambulatory children with cerebral palsy in structures of care or in liberal sector

AbstractAimsTo describe the rehabilitation of non-ambulatory children with cerebral palsy and to explore adjustability on their individual needs.Material and methodData described are extracted from an on-going national cohort study, following during 10years 385 children with cerebral palsy, aged from 4 to 10, Gross Motor Function Classification System IV and V. We analysed data from the first 190 patients (mean age 6years 10months (SD 2.0), 111 boys), focusing on physiotherapy, ergotherapy, psychomotility and speech therapy in medico-social and liberal sectors.ResultsIn medico-social sector, duration of paramedical care is significantly more important than in liberal sector (structure of care: median=4.25h/week, liberal sector: median=2.00h/week) (P<0.0001). More than 4 different types of care per week are given in medico-social sector, while in liberal sector children benefit from only 2 different types of care a week. In investigators opinion, rehabilitation in structures of care is 71.65% adapted as opposed to 18.75% in the liberal sector (P<0.001). Children level V have less time of rehabilitation than the others (P=0.0424).InterpretationRehabilitation of children with cerebral palsy who are not able to walk, with an objective to improve quality of life, is truly multidisciplinary and suitable in medico-social sector

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Fluconazole in hypercalciuric patients with increased 1,25(OH)(2)D levels: the prospective, randomized, placebo-controlled, double-blind FLUCOLITH trial

International audienceBACKGROUND: Hypercalciuria is one of the most frequent metabolic disorders associated with nephrolithiasis and/or nephrocalcinosis possibly leading to chronic kidney disease (CKD) and bone complications in adults. Orphan diseases with different underlying primary pathophysiology share inappropriately increased 1,25(OH)(2)D levels and hypercalciuria, e.g., hypersensitivity to vitamin D and renal phosphate wasting. Their management is challenging, typically based on hyperhydration and dietary advice. The antifungal azoles are known to inhibit the 1α-hydroxylase and therefore decrease 1,25(OH)(2)D levels; they are commonly used, with well described pharmacokinetic and tolerability data. Fluconazole has been successfully reported to reduce calciuria in patients with CYP24A1 or SLC34A3 mutations, with no safety warnings. Thus, based on these case reports, we hypothesize that fluconazole is effective to decrease and normalize calciuria in patients with hypercalciuria and increased 1,25(OH)(2)D levels. METHODS: The FLUCOLITH trial is a prospective, interventional, randomized in parallel groups (1:1), placebo-controlled, double-blind trial. A total of 60 patients (10-60 years) with nephrolithiasis and/or nephrocalcinosis history, hypercalciuria (\textgreater 0.1 mmol/kg/day), increased 1,25(OH)(2)D levels (\textgreater 150 pmol/L), and 25-OH-D levels \textgreater20 nmol/L will be included. Inclusions will be performed only from mid-September to the beginning of February to avoid bias due to sunlight-induced vitamin D synthesis. The primary endpoint will be the proportion of patients with normalization of 24-h calciuria between baseline and 16 weeks, or with a relative decrease of at least 30% of 24-h calciuria in patients who still display at W16 a 24-h hypercalciuria. DISCUSSION: The current challenge is to propose an efficient treatment to patients with hypercalciuria and increased 1,25(OH)(2)D levels in order to prevent later complications and notably CKD that can ultimately lead to end-stage renal disease. Based on improvement of knowledge in phosphate/calcium metabolism, pathophysiology and genetics, the "off-label" use of fluconazole was recently reported to be useful in hypercalciuric patients with increased 1,25(OH)(2)D levels. Thus, the FLUCOLITH study is a unique opportunity to develop a new indication of a well-known and not expensive drug in orphan renal diseases, the ultimate objective being the secondary prevention of CKD worsening in these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04495608 . Registered on July 23, 2020

Management of adolescents with very poorly controlled type 1 diabetes by nurses: a parallel group randomized controlled trial

International audienceBACKGROUNDS: Fluctuation in glycemia due to hormonal changes, growth periods, physical activity, and emotions make diabetes management difficult during adolescence. Our objective was to show that a close control of patients' self-management of diabetes by nurse-counseling could probably improve metabolic control in adolescents with type 1 diabetes. METHODS: We designed a multicenter, randomized controlled, parallel group, clinical trial. Seventy seven adolescents aged 12-17 years with A1C \textgreater8% were assigned to either an intervention group (pediatrician visit every 3 months + nurse visit and phone calls) or to the control group (pediatrician visit every 3 months). The primary outcome was the evolution of the rate of A1C during the 12 months of follow-up. Secondary outcomes include patient's acceptance of the disease (evaluated by visual analog scale), the number of hypoglycemic or ketoacidosis episodes requiring hospitalization, and evaluation of A1C rate over time in each group. RESULTS: Seventy-seven patients were enrolled by 10 clinical centers. Seventy (89.6%) completed the study, the evolution of A1C and participants satisfaction over the follow-up period was not significantly influenced by the nurse intervention. CONCLUSION: Nurse-led intervention to improve A1C did not show a significant benefit in adolescents with type 1 diabetes because of lack of power. Only psychological management and continuous glucose monitoring have shown, so far, a slight but significant benefit on A1C. We did not show improvements in A1C control in teenagers by nurse-led intervention. TRIAL REGISTRATION: Clinical Trials.gov registration number: NCT00308256, 28 March 2006

Adherence to cysteamine in nephropathic cystinosis: A unique electronic monitoring experience for a better understanding. A prospective cohort study: CrYSTobs

International audienceINTRODUCTION: In nephropathic cystinosis (NC), adherence to cysteamine remains challenging; poor adherence is worsening the disease progression with a decline of kidney function and increase of extrarenal morbidities. Our objective was to describe adherence to cysteamine in NC patients, using electronic monitoring systems. METHODS: Patients with confirmed NC, aged \textgreater 4 years and receiving oral cysteamine (short acting or delayed release formulation as standard of care) from 3 French reference centers, were included. Adherence to treatment was primarily assessed as the percentage of days with a good adherence score, adherence score rating from 0 (poor) to 2 (good). A descriptive analysis was performed after 1-year follow-up. RESULTS: Seventeen patients (10 girls, median age: 13.9 (5.4-33.0) years) were included. Median age at diagnosis was 17.0 (3.0-76.9) months and age at start of cysteamine was 21.0 (15.5-116.3) months. Median daily dose of cysteamine was 1.05 (0.55-1.63) g/m(2)/day. Over the year, the median percentage of days with a good adherence score was 80 (1-99)% decreasing to 68 (1-99)% in patients \textgreater 11 years old. The median of average number of hours covered by treatment in a day was 22.5 (6.1-23.9) versus 14.9 (9.2-20.5) hours for delayed release versus short acting cysteamine. CONCLUSION: Our data are the first describing a rather good adherence to cysteamine, decreasing in adolescents and adults. We described a potential interest of the delayed release formulation. Our data highlight the need for a multidisciplinary approach including therapeutic education and individualized approaches in NC patients transitioning to adulthood. Graphical abstract