[Adolescents with cancer: a specific population].
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Adolescent↗
Biomedical subjects
B Lacour
Publications and source records attributed to B Lacour.
Quality, comparability and methods of analysis of data on childhood cancer in Europe (1978-1997): report from the Automated Childhood Cancer Information System project.
In collaboration with 62 population-based cancer registries contributing to the Automated Childhood Cancer Information System (ACCIS), we built a database to study incidence and survival of children and adolescents with cancer in Europe. We describe the methods and evaluate the quality and internal comparability of the database, by geographical region, period of registration, type of registry and other characteristics. Data on 88,465 childhood and 15,369 adolescent tumours registered during 1978-1997 were available. Geographical differences in incidence are caused partly by differences in definition of eligible cases. The observed increase in incidence rates cannot be explained by biases due to the selection of datasets for analyses, and only partially by the registration of non-malignant or multiple primary tumours. Part of the observed differences in survival between the regions may be due to variable completeness of follow-up, but most is probably explained by resource availability and organisation of care. Further standardisation of data and collection of additional variables are required so that this study may continue to yield valuable results with reliable interpretation.
Adolescent↗
Thyroid cancer incidence and survival among European children and adolescents (1978-1997): report from the Automated Childhood Cancer Information System project.
Data on 1690 childhood and adolescent cases of thyroid cancer registered in 61 European cancer registries were extracted from the database of the Automated Childhood Cancer Information System (ACCIS) and included in analyses of incidence and survival. In 1988-1997, the age-standardised incidence rates (ASR) for children aged 0-14 years varied in European regions from 0.5 to 1.2 per million and the age-specific incidence in adolescents aged 15-19 years ranged from 4.4 to 11.0 per million. Over the age-span 0-19 years, the female to male ratio increased from 1 to around 3. Papillary thyroid cancer accounted for almost 65% of cases in children and 77% in adolescents. In the childhood population of Belarus, the ASR for 1989-1997 was 23.6 per million and the proportion of papillary tumours was 87%. No association was found between thyroid cancer risk and national dietary iodine status across 16 countries. Incidence of thyroid carcinoma among children and adolescents in Europe (excluding Belarus) increased during 1978-1997 by 3% per year, largely due to papillary carcinoma. Survival of children and adolescents was high over the entire study period and in all regions of Europe. Children with medullary carcinoma had slightly lower 5-year survival (95%, 95% CI 81-99), than those with papillary carcinoma (99%, 95% CI 95-100). More than 90% of patients survived 20 years after diagnosis. Further standardisation of diagnostic, classification and registration criteria will be fundamental for future studies of thyroid carcinomas in young people.
Adolescent↗
Pleiotropic effects of the non-calcium phosphate binder sevelamer.
The number of chronic kidney disease (CKD) patients and related adverse outcomes has dramatically increased worldwide in the past decade. Therefore, numerous experimental and clinical studies have recently addressed the underlying mechanisms, in particular the marked increase in cardiovascular mortality. Hyperphosphatemia is a major problem in these patients with advanced stage of CKD. Its control by calcium-containing phosphate binders is effective, but at the price of potentially noxious calcium overload. Sevelamer hydrochloride is a phosphate binder that offers an effective control of hyperphosphatemia as calcium-rich binders but without increase of calcium load. Beyond the control of phosphate, sevelamer seems to exert pleiotropic effects which include the correction of lipid abnormalities and the clearance of some uremic toxins.
Chelating Agents↗
[Lorraine childhood cancer registry: incidence, survival 1983-1999].
BACKGROUND: Cancer in childhood account for less than 1% of all cancers and for the second most important cause of death for children aged less than 15 years in France, injuries being the leading cause. Compared to adult cancers, childhood cancers' particularities justify to create pediatric registries. The first French population-based registry was created in Lorraine in 1983. The incidence and survival results from a 17 year-period are presented. METHODS: In Lorraine region, all children (0-14 years) with cancer diagnosed between 1983 and 1999 were included. Crude, age-standardized (world population) and cumulative incidence rates were calculated just as overall, specific-disease and event-free survival rates, using Kaplan-Meier methods. RESULTS: With 1086 registered cases, the crude incidence rate per million children is 132.4, the age-standardized incidence rate per million is 137.5; 1 out of every 500 children will develop cancer before the age of 15 years. The incidence of all cancers combined is slightly higher in males than in females with a M/F ratio of 1.13. For this 17 years-period, no trend in childhood cancer incidence is observed. The main cancer groups are leukemia (30.7%), brain and spinal tumors (23.2%) and lymphomas (12.9%), sympathetic nervous system tumors (7.4%), soft-tissue sarcomas (6.1%), renal tumors (5.2%), and bone tumors (5.0%). Five-year specific survival rates for all cancers combined is 71.4% [95% CI: 68.5-74.3]. The prognosis is significatively worse for the<1 year age group (55%) and for some histologic types: brain stem gliomas (27%), hepatic tumors (43%), osteosarcomas (57%), neuroblastomas (65%), rhabdomyosarcomas (55%). DISCUSSION: Relative distribution of histologic groups, incidence and survival rates observed in Lorraine registry are compatible with the general pattern in the European Union cancer registries. The lack of significative trend in incidence unlike others country may be explained by too small numbers. CONCLUSION: The acquired experience in developping this regional registry allowed us to create a national registry of childhood solid tumors and contribute to valid national data.
Adolescent↗
Dysregulation of superoxide dismutase in chronic kidney disease.
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Chronic Disease↗
[Contribution of national paediatric cancer registries to survey and research].
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Biomedical Research↗
Prenatal diagnosis of spinal muscular atrophy by genetic analysis of circulating fetal cells.
Spinal muscular atrophy (SMA) has a prevalence of one in 6000 births and a one in 40 heterozygote frequency. We aimed to develop a routine test for non-invasive prenatal diagnosis. We tested blood with ISET (isolation by size of epithelial tumour or trophoblastic cells) in 12 pregnant women whose babies were at risk of SMA. Using genetic analysis of fetal cells, we identified SMA in all nine isolated from the three mothers carrying an affected child. There was no mutation in any of the 26 fetal cells isolated from the nine women with an unaffected child. Our results show that non-invasive detection of genetic diseases by the analysis of maternal blood is feasible.
Female↗
Absorption and efficiency of insulin after oral administration of insulin-loaded nanocapsules in diabetic rats.
Poly(isobutylcyanoacrylate) nanocapsules have been shown to decrease the blood glucose level after oral administration to streptozotocin-induced diabetic fasted rats after 2 days [Diabetes 37 (1988) 246]. Yet, the absorption of insulin in the blood of rats has not been characterised. The aim of this work was to evaluate the biological activity of insulin given orally as nanocapsules. Humalog-loaded nanocapsules (50 IU/kg) were administered by gavage to streptozotocin-induced diabetic rats. Thirty minutes to 1 h after oral administration, significant levels of human insulin were detected in rat plasma. However, the concentrations were very heterogenous from one rat to another and no decrease of glycemia could be observed. In addition, parenteral injection of insulin in solution showed that high levels of the protein are necessary to decrease blood glucose concentration in diabetic rats. These concentrations were not reached after oral administration. The same dose of insulin decreased glycemia by 50% in normal rats and by only 25% in diabetics. This suggested that an insulino-resistance was developed by streptozotocin-induced diabetic rats.
Animals↗
Intestinal absorption and metabolism of chlorpheniramine enantiomers in rat.
Chlorpheniramine (CPAM) is a chiral antihistaminic drug commercialized as a racemic mixture. The intestinal absorption and metabolism of CPAM have been investigated in rat using in vivo (oral and IV administration), in situ (intestinal loop model), and in vitro (everted sac model) experiments. Oral and IV administrations of 20 mg/kg of the racemic mixture show that the pharmacokinetics of CPAM are stereoselective, with higher AUCs for the (+)-S-enantiomer compared to its antipode. The monodesmethyl metabolite (DCPM) was quantifiable in blood and its pharmacokinetics are stereoselective after oral but not after IV administration. Experiments using intestinal loops and everted sacs showed that the absorption is not stereoselective and that in vivo stereoselective formation of DCPM is presumably due to stereoselective hepatic metabolism. Moreover, the in vitro and in situ absorption of CPAM are not modified by modulators of P-glycoprotein and cytochromes P450 (cyclosporin A, ketoconazole).
Animals↗
Effect of ethanol and ether in the prevention of calcification of bioprostheses.
BACKGROUND: Lipids play a significant role in the process of calcification of bioprostheses. We assessed whether lipid extraction by ethanol, ether, or a surfactant could mitigate calcification of glutaraldehyde-treated bioprostheses. METHODS: On 200 bovine pericardium samples pretreated with 0.6% glutaraldehyde, lipid extraction was carried out by ethanol, ether, or the tween 80 surfactant, and combinations thereof. The treated tissues were implanted subcutaneously in 50 juvenile rats for 4 and 6 months. Lipids were analyzed by Fourier transform infrared spectrophotometer and chromatography before implantation. Calcium content of implanted tissues was assessed by atomic absorption spectrometer. RESULTS: Ethanol, ether, or surfactant did mitigate calcification. The most efficient pretreatments were the combination of ethanol and surfactant (calcium content: 15.5+/-6.8 microg/mg dry tissue after 6 months implantation) or the combination of ethanol, ether, and surfactant (13.1+/-6.2 microg/mg dry tissue) when compared with surfactant alone (42.9+/-12.7 microg/mg dry tissue). CONCLUSIONS: Ethanol or the combination of ethanol and ether added to the currently used glutaraldehyde-surfactant treatment further mitigates calcification.
Animals↗
Role of oxidized low-density lipoprotein in the atherosclerosis of uremia.
Lipoprotein oxidation is involved in the genesis of atherosclerosis. In chronic renal failure (CRF), oxidative stress is enhanced because of an imbalance between pro-oxidant and antioxidant systems. Oxidative modifications of low-density lipoproteins (LDLs) occur not only at the level of lipid moiety, but also of protein moiety. We have shown that oxidation of LDL by hypochlorous acid (HOCl) in vitro, reflecting increased myeloperoxidase activity in vivo, leads to modifications of apoliproteins such that the latter in turn are capable of triggering macrophage nicotinamide adenine dinucleotide phosphate-oxidase activation. These oxidative changes of LDL protein moiety, if shown to occur to a significant extent in uremic patients in vivo, may represent an important alternative pathway in the pathogenesis of atheromatous lesions.
Arteriosclerosis↗
Oxidative stress and haemodialysis: role of inflammation and duration of dialysis treatment.
BACKGROUND: Oxidative stress has long been demonstrated in haemodialysis patients. However, the factors influencing their oxidative status have not been characterized extensively in these patients. Therefore, the present study was designed to investigate the influence of a large number of factors known to be associated with oxidative stress. METHODS: In the present cross-sectional study, we determined the plasma levels of lipid and protein oxidation markers in 31 non-smoking haemodialysis patients and 18 non-smoking healthy subjects, together with various components of the antioxidant system at the plasma and erythrocyte level. RESULTS: No influence of age, diabetes or iron overload on oxidative markers and plasma and erythrocyte antioxidant systems was detected in these haemodialysis patients. The lack of an association between iron overload and oxidative status may be related to the lower level of plasma ascorbate in haemodialysis patients, since ascorbate favours the generation of free iron from ferritin-bound iron. Interestingly, plasma C reactive protein (CRP) levels measured by highly sensitive CRP assay were correlated positively with plasma levels of thiobarbituric acid reactive substances (r=0.38, P<0.04) and negatively with plasma alpha-tocopherol levels (r=-0.46, P<0.01). Moreover, significant inverse correlations were observed between duration of dialysis treatment and plasma levels of alpha-tocopherol (r=-0.49, P<0.02) and ubiquinol (r=-0.40, P<0.05). CONCLUSIONS: Our results suggest that inflammatory status and duration of dialysis treatment are the most important factors relating to oxidative stress in haemodialysis patients.
Adult↗
Effect of chronic renal failure on the expression and function of rat intestinal P-glycoprotein in drug excretion.
BACKGROUND: In chronic renal failure, the renal excretion of certain drugs is dramatically reduced. To determine whether other routes of drug elimination, such as secretion through the intestinal barrier by intestinal P-glycoprotein can be altered, we compared P-glycoprotein activity, P-glycoprotein protein content, and P-glycoprotein mRNA levels in intestine of control and chronic renal failure rats. METHODS: Chronic renal failure was surgically induced in rats by partial (7/8) nephrectomy. After 5 weeks, intestinal transport of rhodamine 123, a P-glycoprotein substrate, was carried out using an in vitro model of everted gut sacs. P-glycoprotein protein content was quantified by enzyme-linked immunosorbent assay and P-glycoprotein mRNA expression was evaluated by semi-quantitative reverse transcriptase polymerase chain reaction. RESULTS: A decrease of intestinal rhodamine 123 transport was observed in chronic renal failure rats, pointing to an inhibition of P-glycoprotein activity. Transport was inhibited in both sham-operated rats and rats with chronic renal failure by verapamil and cyclosporin A, but relative inhibition vs baseline was less marked in chronic renal failure than in sham-operated rats. In contrast, no significant differences in levels of P-glycoprotein protein or mRNA were observed between the two groups. CONCLUSIONS: Intestinal secretion of rhodamine 123 is mainly mediated by P-glycoprotein. It was reduced in rats with chronic renal failure, reflecting reduced intestinal drug elimination via a decrease in P-glycoprotein transport activity rather than via protein underexpression.
ATP Binding Cassette Transporter, Subfamily B↗
[Clinical coding in oncology].
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Hospitalization↗
High serum apolipoprotein AIV levels in renal transplant recipients.
BACKGROUND: Human apolipoprotein (apo) AIV might play a role in post-transplant reverse cholesterol transport, which appears to be comparable to that seen in healthy subjects. However, there may be subtle differences between healthy individuals and renal transplant recipients, given the other abnormalities of lipoprotein metabolism in the latter. Therefore, the aim of the present study was to investigate possible changes of serum apo AIV levels in renal transplant recipients, and to evaluate potential factors influencing these levels. PATIENTS AND METHODS: Total and free serum apo AIV was determined in 36 clinically stable renal transplant recipients and in 20 sex- and age-matched healthy control subjects. RESULTS: Mean total serum apo IV concentrations (+/- SD) were significantly higher in renal transplant recipients than in control subjects (202 +/- 102 vs 79 +/- 45 mg/l, p < 0.01). The percentage of lipoprotein-free fractions of apo AIV was comparable in both groups. The elevated total serum concentrations of apo AIV were mainly related to creatinine clearance and partially to serum triglyceride levels in renal transplant recipients. CONCLUSION: Our data suggest that the observed elevation of serum apo AIV concentrations in renal transplant recipients is essentially related to the presence of impaired renal function.
Adult↗
[Effects of diuretic therapy on spontaneous expulsion of urinary calculi, urinary pH, and crystalluria in lithiasic patients].
OBJECTIVE: High urine volume is known to be an effective measure for preventing stone recurrence. However, only few studies have investigated its effects on crystalluria and spontaneous passage of calculi. The aim of the study was to assess the effects of high diuresis on stone expulsion and recurrence. PATIENTS AND METHODS: 219 patients were consulting for a first stone episode in Urology units in the Mostaganem area between September 1996 and December 1999. All stones were under 6 mm in size. The patients were divided in two groups: group I included 129 patients (68 males, 61 females) who agreed to be on a high water intake, at least 3 liters per day, over a two months period and to be followed periodically by crystalluria examination in the first morning urine; group II included 90 patients (63 males, 27 females) who declined diuresis advice and urine collection for crystalluria examination. First morning urine collected in patients of group I were examined before (2.95 voidings per subject) and while on diuresis course (2.84 voidings per subject). For each sample, the urine pH was measured and crystals were looked for by polarizing microscopy. Stones spontaneously passed were collected and analyzed by infrared spectroscopy. Group II represented the control group for stone passing and recurrence. RESULTS: Crystalluria was present in 52.4% of urine samples before starting diuresis and decreased at 22.9% of urine samples on high diuresis. Mean pH value increased from 5.73 +/- 0.46 before to 6.09 +/- 0.47 (p < 10-6) while on diuresis course in males and from 5.8 +/- 0.68 to 6.24 +/- 0.66 in females (p < 10-6). The most frequent crystalline species was weddellite. Over the study period, 98 patients (76%) in group I and only 13 patients (14.4%) in group II passed stones spontaneously (p < 10-6 contre group I). No stone recurrence was observed in group I while 37.8% of patients in group II presented at least one stone recurrence (p < 10-7). CONCLUSION: A high diuresis is an effective measure (1) to make easier the passing of stone under 6 mm in size; (2) to reduce the occurrence of crystalluria; (3) to reduce significantly, because of its favourable effect on urine pH, the formation of pH-dependent crystalline phases, thus decreasing heterogeneous nucleation process of calcium oxalate and stone recurrence.
Adolescent↗
Caspase-dependent apoptosis in THP-1 cells exposed to oxidized low-density lipoproteins.
Oxidized low-density lipoproteins (oxLDL) play a critical role in atherogenesis. We investigated the apoptotic process in human monocytic THP-1 cell line, exposed to oxLDL generated by treatment of native LDL either with hypochlorous acid (HOCl), mainly affecting the protein moiety, or with copper sulfate (CuSO(4)), mainly affecting the lipid moiety. After incubation with both types of oxLDL, we observed: (i) microscopy signs of apoptosis in THP-1 cells, (ii) a significant increase of apoptotic cells proportional to LDL protein concentration, either by annexin V or by cell cycle phase analysis with propodium iodide flow cytometry, (iii) a reduction of THP-1 cell apoptosis in presence of the caspase inhibitor Z-VAD.fmk, (iv) the resistance of THP-1 cells apoptosis after PMA-elicited differentiation. In conclusion, HOCl-oxLDL are as potent as Cu-oxLDL to induce high rates of apoptosis in monocytes through a caspase-dependent pathway. Moreover, the resistance of differentiated THP-1 cells to oxLDL-induced apoptosis is compatible with the hypothesis that mature macrophages have prolonged survival and thereby enhance the atherogenic process.
Amino Acid Chloromethyl Ketones↗