A step towards cinacalcet testing for the diagnosis of primary hyperparathyroidism: comparison with the standardized intravenous calcium loading. A pilot study.

OBJECTIVE: A calcium load to suppress parathyroid hormone (PTH) secretion can help to perform the diagnosis in some case of primary hyperparathyroidism (PHPT) with atypical presentation. A similar test with calcimimetic, which avoids hypercalcaemia, would be of interest. Our proof of concept study was conducted to compare firstly the results of a single-dose cinacalcet testing with those of the standardized short-time calcium load in healthy control (HC) and secondly the results of the single-dose cinacalcet testing in HC and in PHPT. METHODS: Twelve HCs received in a random order, at a 2-week interval, either 0·33 mmol/kg calcium gluconate intravenously for 3 h, or a single oral dose of 30 mg or 60 mg cinacalcet. Twelve PHPTs received 30 mg cinacalcet and twelve other PHPTs 60 mg cinacalcet orally. Calcaemia and serum PTH levels were measured basally and then hourly for 6 h. RESULTS: In HC, plasma calcium did not significantly change after cinacalcet intake, whereas calcaemia rose up to 3·47 ± 0·05 mmol/l (mean ± SEM) at the end of the calcium load. PTH dropped from basal level to a similar extend (≥80%) with 60 mg cinacalcet and calcium load, whereas the decrease was significantly lesser (P < 0·01) with 30 mg cinacalcet. In PHPT, serum PTH levels dropped by 44·8 ± 6·9% and 58·2 ± 5·3% 1 h after the respective intake of 30 and 60 mg cinacalcet. One hour after the oral intake of 60 mg cinacalcet, serum PTH levels were <8 ng/l in HC and ≥8 ng/l in PHPT. CONCLUSION: Sixty milligrams of cinacalcet provides similar results as the standardized calcium load test; PHPT patients have a lower response to 60 mg cinacalcet than HC.

[Vitamin D status in 6- to 10-year-old children: a French multicenter study in 326 children]. / Statut en vitamine D des enfants de 6 à 10ans : étude nationale multicentrique chez 326 enfants.

OBJECTIVE: To assess the vitamin D status of children aged 6-10years in the French general population for whom no guidelines have yet been defined due to insufficient data. METHOD: The study was conducted during two winters with very different sunshine levels: 5 March to 17 April 2012 and 8 January to 16 April 2013 in 20 then 22 centers. Three hundred children (60 children for each year of age) attending an ambulatory care unit or outpatient department for a reason unrelated to vitamin D status were included at the end of winter in 20 hospital centers (ten centers in the northern half of France above latitude 46-47°N/Lille: 50°N and ten centers in the southern half of France below latitude 46-47°N/Marseille: 43°N). Centralized 25 hydroxyvitamin D (25(OH)D), alkaline phosphatase (ALP), and parathormone (PTH) assays were performed on leftover blood samples. The currently accepted normal range for 25(OH)D was used to define the following categories: ≤25nmol/L: severe vitamin D deficiency, 25nmol/L100nmol/L: high vitamin D status. A standardized questionnaire was used to collect the child's characteristics, use of a vitamin D supplement, and milk and dairy product intake. The cumulative number of hours of sunshine over the 90days prior to inclusion in each center was obtained from the Météo-France weather bureau. RESULTS: 25(OH)D assays were performed in 326 children; more than 95% of children received milk and dairy products and 38% had received a vitamin D supplement since starting the school year: 3.1% of children in the overall population presented severe vitamin D deficiency, 34.4% presented vitamin D deficiency, 53.1% had a sufficient vitamin D status, and 9.5% had a 25(OH)D concentration >100nmol/L with no impact on serum calcium and urinary calcium. Children living in the north of France generally had lower 25(OH)D levels than children living in the south of France. In the non-supplemented population (n=188), 5.3% of children presented severe vitamin D deficiency, 45.2% presented vitamin D deficiency and 48.4% had sufficient 25(OH)D levels. The percentage of children with severe vitamin D deficiency or vitamin D deficiency was twofold higher during the winter with poor sunshine compared to the sunnier winter with a less marked north/south difference. No case of severe vitamin D deficiency was observed in the supplemented population (n=119); 10-15% of children presented vitamin D deficiency and 22.7% had a 25(OH)D concentration >100nmol/L, while remaining within the acceptable range. Two cases of hypervitaminosis without hypercalcemia were identified: one after an unknown loading dose with a calcium/creatinine ratio in the normal range (0.8); for the second one, no additional information could be obtained. Vitamin D supplementation considerably reduced the north/south difference and the Winter1/Winter2 difference. A child not receiving a vitamin D supplement had a ninefold higher risk of vitamin D deficiency at the end of winter than a child receiving a vitamin D supplement (OR=8.8; 95%CI, 4.6-16.8). CONCLUSION: At least one-third of children aged 6-10years presented deficient 25(OH)D levels. None of the children receiving a vitamin D supplement presented severe vitamin D deficiency, only a small number of children presented vitamin D deficiency (n=16 (13.4%)), and no signs of overload were observed, while one half of non-supplemented children (n=95 (50.5%)) presented at least vitamin D deficiency at the end of winter. These results support the need for vitamin D supplementation during winter in children aged 6-10years.

Glucose-induced incretin hormone release and insulin sensitivity are impaired in patients with idiopathic gastroparesis: results from a pilot descriptive study.

BACKGROUND: Incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)] released by the gut modulate gastrointestinal motility and influence gastric emptying (GE). Abnormal secretion or sensitivity to these hormones could contribute to the pathogenesis of gastroparesis. The aim of this study was to investigate incretin hormone secretion during a prolonged oral glucose load in non-diabetic patients with documented idiopathic gastroparesis. METHODS: Fifteen patients referred for digestive postprandial discomfort with delayed GE demonstrated by a (13) C-labeled octanoate breath test were included and compared with 10 healthy controls. A 75 g oral glucose load was performed, with blood samplings every 30 min for 5 h, to determine glucose, insulin, GIP, and GLP-1 blood levels. KEY RESULTS: Fasting GIP concentration was significantly higher in the patient group (56.1 ± 5.8 pg mL(-1) vs 29.9 ± 7.7 pg mL(-1), P =0.012). Postglucose load GIP concentrations were also significantly elevated in patients with gastroparesis, whereas GLP-1 concentrations during fasting and postglucose load conditions were not different to those of healthy controls. Moreover, glucose tolerance during glucose load was abnormal in patients, combining hyperglycemic insulin resistance and hyperinsulinism patterns, while fasting values for glycemia, insulin sensitivity, and insulin concentrations were normal. CONCLUSIONS & INFERENCES: Patients with idiopathic gastroparesis exhibit abnormal GIP levels associated with impaired insulin sensitivity during oral glucose load. Further studies are needed to establish the involvement of these defects in the pathophysiology of gastroparesis.

[Prophylactic prescription of vitamin D in France: national multicenter epidemiological study of 3240 children under 6 years of age]. / Prescription prophylactique de la vitamine D en France : enquête épidémiologique multicentrique nationale chez 3240 enfants de moins de 6 ans.

AIMS: The aim of the study was to assess compliance with the current recommendations of prophylactic prescription of vitamin D via a multicentric cross-sectional epidemiological survey of 3240 children under 6 years of age. METHOD: Parent questionnaires and data from the health records of children presenting to the emergency departments of 25 teaching hospitals and hospital centers provided information on the children's characteristics, their prescriptions, and other vitamin D intake. Based on the currently applicable recommendations, intakes of 600-1,200 IU/day - 900-1500 IU/day for children with pigmented skin and/or premature and/or hypotrophic children - are considered adequate. RESULTS: In 1606 infants, 9.8% of the prescriptions were below and 23.7% were above the recommendations; in 1256 children between 18 months and 5 years of age, 53.4% of the prescriptions were below and 5.1% were above the recommendations. Children at risk, those from the southern half of France, and those between 18 months and 5 years of age were more likely to receive a prescription below the recommendations; their risk of receiving a prescription above the recommended guidelines was smaller. Of the children aged between 61 and 71 months, 85% had not received any prescription at all during the previous 12 months. These results were compared with the laboratory data collected from a subsample of children. There was a significant correlation between the adequacy of the prescription and the biological vitamin D status both for 25-hydroxyvitamin D (25-OH-D) serological concentrations and for calciuria. CONCLUSIONS: Only 66.6% of the prescriptions in children between 0 and 18 months of age and 41.5% in children between 19 months and 5 years of age comply with the recommendations; 53.4% of the prescriptions in the latter age group are below the current recommendations.

The new haematology analyzer DxH 800: an evaluation of the analytical performances and leucocyte flags, comparison with the LH 755.

INTRODUCTION: The analytical performance and the abnormality messages on differential (flags) of the new analyzer Beckman Coulter DxH 800 were compared with those of the LH 755. METHODS: First, we evaluated the accuracy of the results of the DxH 800, in comparison with the LH 755, in 125 samples without alarm using unflagged sample results on both analyzers. Second, flagged samples on the LH 755 but not flagged by the DxH 800 were evaluated by flow cytometry for accuracy of the DxH 800 results. Finally, we evaluated the sensitivity and specificity of abnormality messages on differential given by the analyzers, in comparison with manual blood smears. RESULTS: The correlation coefficients (R) for complete blood count parameters and differential demonstrated that the DxH 800 results were similar to that of LH 755. Excellent correlation coefficients between DxH 800 and flow cytometry results were found for white blood cell count (R = 0.985, n = 31), platelet count (R = 0.976, n = 51) and nucleated red blood cells (R = 0.966, n = 37). The overall performance showed an increased sensitivity (0.892) and specificity (0.864) of the flags on DxH 800 when compared to the LH 755 (0.846 and 0.733, respectively). CONCLUSION: The DxH 800 provides reliable results and increases laboratory efficiency by reducing working time and costs associated with the optical validation of the results.

[Administration of a single Winter oral dose of 200,000 IU of vitamin D3 in adolescents in Normandy: evaluation of the safety and vitamin D status obtained]. / Administration orale hivernale d'une dose unique de 200 000 UI de vitamine D3 chez l'adolescent en région normande: évaluation de sa tolérance et du statut vitaminique D obtenu.

Adolescence, a period of growth and acquisition of bone mass, requires adequate calcium and vitamin D intake. This study was designed to assess the impact of a single loading dose of 200,000 IU of vitamin D(3) on the winter vitamin D status of healthy adolescents. Vitamin D status was assessed by 25-OH-D levels before, 3 weeks, and 3 months after this single dose, and safety was assessed by serum calcium and PTH and urinary calcium excretion in random samples from 27, 23, and 17 healthy adolescents derived from the same institution. The 25-OH-D peak value 2 weeks after the vitamin D supplement of 71-129 nmol/l (mean, 96 nmol/l), and a residual level at 3 months of 29-83 nmol/l (mean, 57 nmol/l) serum calcium and urinary calcium excretion expressed by the calcium/creatinine ratio were normal and stable at 2 weeks and 3 months, remaining less than 0.5 for the calcium/creatinine ratio. This simple measure, ensuring good compliance during adolescence, ensures optimal winter vitamin D status with no signs of overload.

Prognostic value of serum CA 125 bi-exponential decrease during first line paclitaxel/platinum chemotherapy: a French multicentric study.

BACKGROUND: CA 125 assays enable treatment-response monitoring in ovarian cancer. METHODS: A multicentric study of CA 125 kinetics under paclitaxel/platinum-based chemotherapy was performed in 130 stage IIc-IV patients. CA 125 half-life and nadir concentration were compared to patient outcome. Some patients (n=38, 29.2%) presented a CA 125 bi-exponential decrease and its clinical implication was studied. Survival analyses for disease-free survival (DFS) and overall survival (OS) used univariate (Kaplan-Meier) and multivariate (Cox model). RESULTS: During a median follow-up time of 29 months (range 5-106 months), 111 patients (85%) relapsed and 94 (72%) died from ovarian cancer. Patients were split into 4 groups according to their pattern of CA 125 decrease: non-assessable half-life because of a low pre-chemotherapy CA 125 level (n=38), half-life < or = 14 days and mono-exponential CA 125 decay (n=18), half-life < or = 14 days and bi-exponential CA 125 decay (n=21), and half-life > 14 days (n=53). In Cox models, nadir concentration, residual tumour volume and number of chemotherapy courses were found to be independent prognostic factors for DFS and OS. The group classification was found to be an independent prognostic factor only for DFS. However, when nadir was not introduced in the models, the CA 125 kinetics groups were the most important prognostic factor for OS. CONCLUSION: Characteristics of CA 125 kinetics during first line paclitaxel/platinum chemotherapy have a strong and independent prognostic value. A CA 125 bi-exponential decrease is an indicator of bad prognosis.

Change in CA 125 levels after the first cycle of induction chemotherapy is an independent predictor of epithelial ovarian tumour outcome.

BACKGROUND: CA 125 assays enable treatment response monitoring in ovarian cancer. PATIENTS AND METHODS: This multicentric study was carried out to assess the prognostic value of the CA 125 change after the first and the second courses of induction chemotherapy (CT). Of the 494 stage IIc-IV patients, 194 had a surgical second look, 397 (80.4%) relapsed and 382 (77.3%) died from cancer. Median (range) follow-up time was 34 months (3-215 months). RESULTS: In Cox models, CA 125 change after the first course (P < 0.0001), residual tumour (P = 0.003), CA 125 before the second course (P = 0.025) and patients' age (P = 0.048) were independent prognostic factors for overall survival (OS). A normal CA 125 before each of the two first CT courses or a CA 125 decrease >50% after the first course with a normal CA 125 before the second course identify patients with good prognosis. Both criteria retained a significant value in predicting second-look findings by univariate and multivariate analysis (P < 0.0001). CONCLUSION: Among well-established prognostic factors in ovarian cancers, the CA 125 change after first course of CT was independent prognostic factors for both achievement of pathological complete response and OS.

CA 125 half-life and CA 125 nadir during induction chemotherapy are independent predictors of epithelial ovarian cancer outcome: results of a French multicentric study.

BACKGROUND: CA 125 assays enable treatment-response monitoring in ovarian cancer. PATIENTS AND METHODS: A multicentric study of CA 125 kinetics under induction chemotherapy was performed in 631 patients. CA 125 half-life was calculated by mono-compartmental logarithmic regression. Nadir CA 125 concentration and time to nadir were also studied. Survival analyses for disease-free survival (DFS) and overall survival (OS) used univariate (Kaplan-Meier) and multivariate (Cox) models. RESULTS: For 553 stage IIC-IV patients, 459 (83.0%) relapsed and 444 (80.3%) died from cancer. Median (range) follow up time was 32 months (2-214 months). Median (range) for CA 125 kinetics were: 263 kU/l (5-52000 kU/l) before 1st course, 15.8 days (4.5-417.9 days) for CA 125 half-life, 16 kU/l (3-2610 kU/l) for nadir and 85 days (0-361 days) for time to nadir. Pre-chemotherapy CA 125, its half-life, nadir concentration and time to nadir all had a univariate prognostic value for DFS and OS (P<0.0001). In Cox models, CA 125 half-life, residual tumour (P<0.0001 for both), nadir concentration (P=0.0002) and stage (P=0.0118) were the most powerful prognostic factors for DFS. For OS, the significant variables were similar, with age ranking last (P=0.0319). CONCLUSION: Among well-established prognostic factors in ovarian cancers, CA 125 half-life and nadir concentration bear a strong and independent prognostic value.

Lymphocyte volume and conductivity indices of the haematology analyser Coulter GEN.S in lymphoproliferative disorders and viral diseases.

The haematology analyser Coulter GEN.S gives a set of data -'positional parameters'- defining white blood cell (WBC) populations by mean of index values (mean and standard deviation of volume, conductivity and scatter, used to identify the WBC populations). The volume and conductivity parameters related to the lymphocytes were analysed at diagnosis in patients suffering from chronic B-lymphocytic leukaemia (B-CLL), other non-CLL lymphoproliferative disorders (OLPD) and viral diseases. The standard deviation of volume index (SDVI) is significantly higher in the three groups, whereas the mean volume index (MVI) is significantly lower in B-CLL, and increased in OLPD and viral diseases. These two groups could be distinguished by their mean conductivity index (MCI), which is significantly lower in viral disease group. Cut-offs were calculated for each parameter by the mean of Receiver Operating Characteristic (ROC) analysis. The study of the detection performances showed that the combination of lymphocyte count with SDVI, MVI and MCI could be used with a good sensitivity and specificity to discriminate between the most frequent lymphocyte pathologies, even in patients with normal lymphocyte count.

[Calcium and D vitamin status in toddlers: original study performed in the area of Rouen]. / Statut calcique et vitaminique D des enfants d'âge préscolaire. A propos d'une enquête pratiquée en région rouennaise.

Few data are available regarding calcium and vitamin D intake in toddlers, despite a remaining high growth velocity. Therefore, a study was carried out in the Rouen geographical area where the sunshine is limited. It appears that a great majority of the children studied (9/10) received plain milk, and subsequently only small quantities of vitamin D or calcium enriched milk. Nevertheless, 12% of primarily 4 to 6 year-old children do not received daily minimum requirements, and 6% of them had vitamin D insufficiency, which was demonstrated by 25OHD plasma concentrations. These concentrations declined from 18 months to 6 years old were related to discontinuation in vitamin D supplements. A great variability was observed in vitamin D supplementation as no official recommendations were followed. Modalities of this supplementation should be reconsidered.

[Interpretation of the CA125 kinetics during first line chemotherapy of the ovarian cancer: methodological aspects and characteristic profiles]. / Interprétation des cinétiques du CA125 sous chimiothérapie de première ligne des cancers de l'ovaire: aspects méthodologiques et profils caractéristiques.

Mathematical analysis of CA125 kinetics during first line chemotherapy allows calculation of various biologic parameters which are powerful indicators of the therapeutic efficiency. The purpose of this study is to present an original method of interpretation of CA125 kinetics based on both CA125 profile and its half-life value. The first part of this study reviews the practical modalities of CA125 kinetics analysis, the methods of calculation of the biologic parameters as well as the guidelines of interpretation. The second part of this work is dedicated to the presentation of CA125 profile characteristics in responders to chemotherapy, partially or totally nonresponders to chemotherapy, tumoral growth under treatment and tumor lysis syndrome.

[Standards, options and recommendations for blood tumor markers in thyroid cancers]. / Standards, Options et Recommandations: marqueurs tumoraux seriques des cancers de la thyroide.

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centers (FNCLCC), the 20 French Cancer Centers and specialists from French Public Universities, General Hospitals and Private Clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To define, according to the definitions of the Standards, Options and Recommendations project, the characteristics of the main tumor markers in thyroid cancer and the potential role of these markers in the management of patients with this malignancy. METHODS: Data were identified by searching Medline and the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 55 independent reviewers, and to the medical committees of the 20 French Cancer Centers. RESULTS: The main recommendations are: 1) Thyroglobulin is a serum tumor marker for the monitoring of operated thyroid differentiated neoplasms (standard). 2) It is essential to know if the patient is under TSH stimulation or under thyroid suppression therapy to interpret thyroglobulin results (standard). 3) Thyroglobulin assay must be performed regularly during the monitoring of differentiated thyroid neoplasms (standard, level of evidence B2), should be coupled with the measurement of anti-thyroglobulin antibodies concentration using a sensitive method (standard, level of evidence B2). 4) Thyroglobulin assay should not be performed to detect or diagnose differentiated thyroid neoplasms (standard, level of evidence B2). 5) The methods used to assay thyroglobulin must have a limit of detection lower than 3 mug.l- 1 (standard, expert agreement). 6) Calcitonin is a marker for medullary thyroid cancer (standard). 7) Its assay, associated with RET gene study if indicated, enables medullary thyroid cancer to be diagnosed. 8) The pentagastrin test is essential to diagnose familial forms of medullary thyroid cancer. 9) All analyses for each patient must be performed in the same laboratory, using the same technique (standard, expert agreement). 10) Calcitonin and carcinoembryonic-antigen are serum markers for the monitoring of medullary thyroid cancer and allow the detection of recurrent disease (standard).