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Biomedical subjects

P Forget

Publications and source records attributed to P Forget.

At least 19 recordsLinked to original sources

[Secondary cancers in childhood].

Improved survival of pediatric cancer patients will lead to an increase of late sequellae such as secondary malignant neoplasms (SMN). Specific pediatric factors predisposing to these SMN are as follows: long expecting duration of life, high cellular proliferative potential, toxicity of often combined cancer therapies (radio- and chemotherapies) and more frequent genetic predisposition to cancer. Better understanding of these factors could improve patients management and could lead to the development of less toxic future therapies with the hope to decrease the risk of SMN.

Chemotherapy, Adjuvant↗

[Acute lymphoblastic leukemia in children].

We report our experience over the last seventeen years (1985-2002) of the treatment of acute lymphoblastic leukemia (ALL) in children at the University of Liege Pediatric Department of Hematogy-Oncology (CHU-Sart Tilman and CHR-Citadelle). Seventy seven children are enrolled in our study; the mean follow-up is 6.7 years. The 5 years over all survival and the disease free survival for the entire group are respectively 83% and 79%. Prognostic factors shown in our study are sex, high white blood cells counts at diagnosis and immunophenotypes.

Adolescent↗

[Clinical evaluation of 23 children with neuroblastoma. The experience of a single institution].

In this retrospective study, we analyse epidemiology, clinical symptoms and therapeutic results in a group of 23 children with neuroblastoma. Half of them were less than 2 years of age; in 19 of 23, the primitive tumour was abdominal; 35% of them were initially metastatic. The overall survival was 83% at 5 years and the event free survival, 75% at 5 years. Pronostic factors are age, extension of the disease at diagnosis, biologic parameters and genetic study of the neuroblast cells (amplification of N-myc oncogen). Our study shows the deleterious effect of bone lesions.

Abdominal Neoplasms↗

[Retrospective study of childhood lymphomas. Report of 27 children treated at a single institution].

Childhood lymphomas represent a heterogeneous group of disorders that are quite different from adult lymphomas. Over the past three decades, empirical chemotherapeutic management has transformed survival figures, and more recently greater understanding of the biology is offering hope for improved management of resistant disease. We present here the experience of a single institution in the management of 27 childhood lymphomas; epidemiological and clinical characteristics are described as well as survival rates. The median follow up of the patients is 4 years 7 months. The five-year overall survival for the entire group is more than 95 %; the 5-year disease free survival is 91,6 % for Hodgkin's lymphomas, 92,8% for non Hodgkin's lymphomas and 100% for Burkitt diseases. Two relapses have occurred and all of them appeared within the 18 months of the diagnosis. No toxic death has been reported.

Adolescent↗

[Infections and antibiotic prophylaxis in sickle cell disease].

Bacterial infections remain a major cause of morbidity and mortality among young children with sickle cell disease. Susceptibility to infections is mainly observed in homozygous sickle cell disease. The incidence of bacteremias in children under 3 years of age is approximately 8 events/100 patient-years among homozygous subjects and approximately S events/100 patient-years among those with SC hemoglobinopathy. Pneumococci and Salmonellae are the most frequently isolated bacteria. Severe clinical manifestations include septicemia, meningitis, osteomyelitis and pneumonia. M. Pneumoniae and C. Pneumoniae infections may be severe and may induce acute chest syndrome. The high incidence and severity of bacterial infections in these children justify prevention efforts by antibiotic prophylaxis and vaccination. The efficacy of oral penicillin prophylaxis against pneumococcal infections has been well demonstrated and is now recommended from 3 months of age. The antipneumococcal conjugate vaccine has been shown to be safe and immunogenic in young infants.

Anemia, Sickle Cell↗

Femtosecond Structural Dynamics in VO2 during an Ultrafast Solid-Solid Phase Transition.

Femtosecond x-ray and visible pulses were used to probe structural and electronic dynamics during an optically driven, solid-solid phase transition in VO(2). For high interband electronic excitation (approximately 5 x 10(21) cm(-3)), a subpicosecond transformation into the high-T, rutile phase of the material is observed, simultaneous with an insulator-to-metal transition. The fast time scale observed suggests that, in this regime, the structural transition may not be thermally initiated.

Journal Article↗

Effect of spermine administration on pancreatic maturation in unweaned rats.

The effect of oral administration of spermine on pancreatic maturation was investigated in the suckling rat. The treatment consisted of 0.3-0.4 mmol spermine kg-1 body weight given orally once a day for 3 days starting at day 11 after birth. Spermine administration does not adversely affect the growth of the pancreas (wet weight, protein and DNA contents remain unchanged). The proliferating cell nuclear antigen (PCNA) index decreases significantly in spermine-treated rats, indicating that spermine slows down the proliferation rate of the organ. The enzymatic activities of trypsin, chymotrypsin and alpha-amylase are increased significantly in the pancreas of spermine-treated rats. The morphology of the organ seems affected as shown by hematoxylin-eosin staining: a cytoplasm indicative of higher synthetic activity is visible after spermine treatment. We conclude that spermine treatment of unweaned rats can induce precocious biochemical and morphological maturation of the exocrine pancreas, pushing the organ forward in the process of differentiation (closer to the adult stage).

Animals↗

Effects of a proton-pump inhibitor in cystic fibrosis.

Most children with cystic fibrosis (CF) show persisting steatorrhoea even when treated with pancreatic enzyme. As a low duodenal pH could be responsible for this persisting fat loss, we evaluated the effects of a proton-pump inhibitor (lansoprazole) on both steatorrhoea and growth parameters in 15 CF patients, aged 3.1-22.6 y. Acid steatocrit, anthropometry and dual-energy X-ray absorptiometry were used to evaluate steatorrhoea and the nutritional status before, during and 3 months after stopping lansoprazole treatment (15 mg/d for 3 months). Mean +/- SD acid steatocrit values decreased from 37.1 +/- 8.8% to 28.5 +/- 10.6% (p = 0.02). Significant mean Z-score improvements were found for weight (+0.14; p = 0.02), height (+0.15; p = 0.03), subscapular (+0.61; p = 0.003), supra-iliac (+0.8; p = 0.002) and the sum of the four measured skinfolds (+0.61; p = 0.002). Z-scores deteriorated again after stopping lansoprazole. Fat mass and bone mineral content increased significantly on lansoprazole (p = 0.008 and p = 0.005, respectively). We conclude that lansoprazole as adjuvant therapy significantly improves both steatorrhoea and the nutritional status in CF children who maintain steatorrhoea while on pancreatic enzymes.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Long term follow-up of patients with acute myelogenous leukemia who received the daunorubicin, vincristine, and cytosine arabinoside regimen.

BACKGROUND: In 1985, the authors published a study of acute myelogenous leukemia (AML) patients treated with a chemotherapeutic regimen that was then considered intensive. Ten years later, the authors reanalyzed the same cohort to determine whether the very promising actuarial results observed at 5 years held after longer follow-up. METHODS: Between 1977 and 1982, 61 patients with AML were treated with a protocol consisting of daunorubicin, vincristine, and cytosine arabinoside induction followed by consolidation and maintenance for a total of 2 years. The complete remission (CR) rate was 66%, 84% in males versus 47% in females (P < 0.005). At the time of the first analysis in 1984, the overall survival (OS) was 17%, the projected 5-year continuous CR rate (CCR) 32%, and the disease free survival (DFS) rate 29%, with the best results observed for males and for patients ages 40-60 years (P < 0.05). RESULTS: When the data were reanalyzed 11 years later in 1995, the results were 14% OS, 23% CCR, and 16% DFS at 5 years. However, these figures dropped to 8%, 18%, and 11% at 10 years and to 8%, 12%, and 7% at 15 years, respectively. Among the 40 CR patients, 31 relapsed (up to 13 years after CR), and all died within 1.6 years after relapse. Nine patients were in CCR: 4 died of unrelated causes (suicide, alcoholic cirrhosis, acute peritonitis, or bladder carcinoma), 1 was lost to follow-up after 11 years, 2 were alive and well at 17 years at last follow-up, and 2 were transplanted in first CR and were doing well at 13 and 14 years at last follow-up. The survival advantage for males over females persisted (P = 0.0197), but the advantage for patients age 40-60 years did not hold. CONCLUSIONS: These long term data indicate that actuarial analysis at 5 years may overestimate the cure rate of AML patients because a number of late relapses do occur. However, the picture is blurred by the incidence of death not related to leukemia or its treatment; and when these patients were censored at the time of death, 17% of CR patients were still projected to be alive and free of leukemia after 17 years.

Adolescent↗

Fecal polyamine concentration in children with and without nutrient malabsorption.

BACKGROUND: Fermentation products of malabsorbed nutrients are thought to be responsible for intestinal adaptation following small bowel resection in rats. It has been suggested that either short-chain fatty acids or polyamines (mainly putrescine and cadaverine) could be the fermentation products involved. There are no data available on fecal polyamine content in humans. The present study compared the fecal polyamine concentrations in children with and without malabsorption. METHODS: Sixteen (8 girls, 8 boys) malabsorption patients (cystic fibrosis: 13, short bowel syndrome: 2, biliary atresia: 1) with a mean age of 8 years were compared to 17 (9 girls, 8 boys) sick children without malabsorption (mean age 5.7 years). Three-day fecal collections were performed and analyzed for fat and polyamine concentrations. High-performance liquid chromatography (HPLC) was used for the measurement of polyamine concentrations. RESULTS: Mean and SEM for fecal fat excretion was 13.4 +/- 2.5 g/day and 1.5 +/- 0.3 g/day in the malabsorption and control group respectively. Median fecal cadaverine and putrescine concentrations were 3723 mumol.kg-1 feces and 4737 mumol.kg-1 feces for the malabsorption group and 114 mumol.kg-1 feces and 306 mumol.kg-1 feces for the control group (p < 0.007 and < 0.00001 respectively). No significant differences were found for fecal spermine and spermidine concentrations between the two groups. CONCLUSIONS: Children with malabsorption show very high fecal putrescine and cadaverine concentrations. Our results support the hypothesis that fecal polyamines could be important.

Adolescent↗

Presence of inducible nitric oxide synthase, nitrotyrosine, CD68, and CD14 in the small intestine in celiac disease.

Celiac disease is characterized by severe inflammation of the small intestine, and inflammation is known to often be associated with enhanced nitric oxide (NO) production. The aim of the present study was to determine whether children with active celiac disease show increased duodenal inducible nitric oxide synthase (iNOS) expression by immunohistochemistry. For this purpose, NO activity was assessed by detection of nitrotyrosine, which is an indicative marker for the formation of the NO- and superoxide-derived oxidant peroxynitrite. Serial staining with the macrophage markers CD68 and CD14 was performed to assess whether intestinal macrophages are involved in intestinal NO production. Duodenal biopsies from seven children with normal biopsy findings were used for comparison. Intense iNOS staining of enterocytes was observed in 10 of 11 celiac disease biopsies but in only 1 of 7 controls (p < 0.002). In addition, nitrotyrosine staining was detected in the enterocytes of celiac disease patients and was associated with iNOS staining. Moreover, the number of iNOS-positive cells in the lamina propria was significantly (p < 0.002) enhanced in patients with celiac disease. Serial staining for iNOS, CD68, and CD14 revealed an increase in CD68/CD14 double-positive monocytes and colocalization of iNOS and CD14 expression associated with this disease. Collectively, these data suggest that in patients with active celiac disease, synthesis of iNOS is induced in the intestine in association with the formation of peroxynitrite and nitration of cellular proteins. Furthermore, the increase in intestinal CD14-positive macrophages suggests a role for these cells in the pathophysiology of the disease.

Antigens, CD↗

Improved steatocrit results obtained by acidification of fecal homogenates are due to improved fat extraction.

Conflicting results have been reported on the value of the steatocrit as a screening test for steatorrhea. We recently modified the test procedure by fecal acidification with the hope of improving fat extraction and consequently the sensitivity of the test. The aim of the present study was to ascertain whether or not fecal acidification led to improved fat extraction by comparing the fat content of both fatty and solid layers obtained by centrifugation of 12 acidified (acid steatocrit) and unacidified (classical steatocrit) steatorrheal stool samples. The fat content of fatty and solid layers was evaluated using the semiquantitative (+ = 1, +2 = 2, +3 = 3) scoring system described by Drummey for the interpretation of the Sudan microscopic method for fecal fat. The fatty layers sum of scores for the 12 samples examined was 31 and 16 for the acid and classical steatocrit, respectively. The solid layers sum of scores for the 12 samples was 13 and 24 for the acid and classical steatocrit, respectively. Fat extraction from stool samples was significantly improved after fecal sample acidification (p < 0.005). Acid steatocrit results agreed better with chemically measured fecal fat than classical steatocrit results. We conclude that fecal acidification, by improving fat extraction, increases the reliability of the steatocrit method for the detection of steatorrhea.

Celiac Disease↗

Acid steatocrit during infancy.

The faecal acid steatocrit is an improved steatocrit method for the evaluation of faecal fat. The present study was set up in order to establish reference values during the first year of life. Faecal acid steatocrit values were determined in 58 healthy full term and in 16 healthy prematurely born infants. Very high acid steatocrit results (above 60%) were found in all premature and many formula-fed term infants during the first 6 months of age, thereafter with values below 10%. In 40- to 120-day-old infants acid steatocrit results of human milk-fed infants were significantly lower than those of formula-fed infants (p < 0.01). We conclude that high acid steatocrit results after the age of 6 months are indicative of fat malabsorption, while before this age high values can be due to "physiological steatorrhoea". The acid steatocrit should be useful for the evaluation of milk fat absorption in infants.

Chemistry, Clinical↗

The acid steatocrit: a much improved method.

The steatocrit method has recently been introduced as a simple screening test for steatorrhea. As it seemed likely that separation of fecal homogenate by centrifugation into a lipid phase, a watery phase, and a solid phase would be pH-dependent, we evaluated the effect of fecal acidification on steatocrit results. We also compared classical and acid steatocrit results in healthy children and in patients with cystic fibrosis and studied the relationship between two steatocrit methods and fecal fat content as measured by a reference chemical method. Steatocrit results increased with the degree of fecal acidification, and maximal results were obtained at the lowest fecal pH values. Means and SEM for classical and acid steatocrit values were 1.1 +/- 0.4% (classical) versus 3.8 +/- 1% (acid) in controls (n = 6) and 5.4 +/- 1.9% (classical) versus 26.9 +/- 4.3% (acid) in cystic fibrosis patients (n = 9). The correlations between fecal fat content measured chemically and steatocrit results were 0.18 (p = 0.35) and 0.81 (p < 0.0001) for classical and acid steatocrit, respectively. We conclude that acidification of fecal homogenates leads to a marked improvement in the steatocrit method.

Celiac Disease↗

Inhibition of vasoactive intestinal peptide (VIP) binding on human melanoma cells IGR39 by nitric oxide: cGMP is not involved.

Nitric oxide (NO) and the NO generating agent nitroprusside (SNP), inhibit the binding of [125I] vasoactive intestinal peptide (VIP) to its receptor at the surface of IGR39 human melanoma cells. Cysteine (10 mM) increases the sensitivity of the system to SNP while N-acetylcysteine (10 mM) decreases it. The NO gas as well as SNP inhibits the [125I]VIP binding capacity. These observations sustain an effect of SNP-generated NO rather than an effect of the SNP molecule per se or the cyanoferrate portion of the molecule. The inhibitory effect of NO is time and concentration dependent and is fully reversible. Affinity constants of high and low affinity VIP receptors of SNP-treated IGR39 cells are not modified while maximal binding capacity (Bmax) of both receptor types are decreased to the same extent. Production of cGMP by SNP-treated cells is time and concentration dependent and the maximum amount of cGMP obtained reaches 13 times the basal level. The cAMP production is not affected by SNP. However, the SNP effects on the [125I]VIP binding are not mimicked by the membrane permeant cGMP analogs dibutyryl cGMP and 8-bromo cGMP even at concentrations as high as 0.5 mM. Taken altogether, these data demonstrate a regulatory action of NO on VIP binding capacity of IGR39 melanoma cells which is not cGMP mediated. They also evidence a new step which could be involved in the NO-VIP interaction.

Cyclic AMP↗