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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The frequency and pattern of obesity in survivors of acute lymphoblastic leukaemia (ALL) was examined in a retrospective analysis of height and weight at zero, two, and four years from diagnosis in 40 children (19 boys and 21 girls). The children had been treated according to the Medical Research Council protocols UKALL VIII and X, both of which included cranial radiotherapy at a dose of 1800 cGy. Body mass index (BMI), determined as weight/height, was used as a measure of fatness. The BMI Z scores were calculated for each patient from standard tables. The ALL group was compared with a control group of 18 age matched children who had received chemotherapy but no radiotherapy. Changes in BMI between diagnosis and two and four years later were analysed by paired t tests. Mean BMI Z scores at diagnosis were similar between ALL boys, ALL girls, and the control group. Two years after diagnosis the ALL group, particularly the girls, showed a significant increase in BMI. By four years BMI had decreased slightly in the ALL boys, but had increased still further in the ALL girls with 57% having BMI Z scores greater than 2. In the control group BMI increased, but not significantly, at two and four years. It is concluded that the obesity seen in patients treated for ALL is more pronounced in girls than boys, and that cranial irradiation is an important factor.
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PMID:Patterns of obesity in boys and girls after treatment for acute lymphoblastic leukaemia. 771 53

Acute lymphoblastic leukaemia (ALL) is one of the readily treatable neoplastic diseases of childhood. One of the late sequelae of treatment can be impaired growth. The authors followed up therefore a group of 63 patients where during childhood a diagnosis of ALL was made. The investigated group was treated according to two fundamental protocols--according to Pinkel's protocol and according to BMF protocols. All patients treated according to Pinkel's protocol had, as part of prevention of leukaemia of the CNS, radiotherapy of the skull, patients treated according to the BMF protocol only when the risk factor was higher than 0.8. The authors investigated in their patients the height and proportionality after termination of all antileukaemic therapy. They found that the height of children, adolescents and adults who suffered from ALL during childhood is average or less. A tendency towards obesity is typical. The authors did not observe a correlation with the total cumulative doses of cytostatics nor a marked correlation with radiotherapy. Impaired growth was more frequent when ALL was diagnosed before the age of 3 years and where the interval after completed therapy was shorter.
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PMID:[Physical development in patients with acute lymphoblastic leukemia in childhood]. 834 57

Late events and side effects are reported in 392 children cured of leukemia. They originated from 1193 consecutively newly diagnosed children between 1972 and 1982, in first continuous complete remission for at least 6 y after diagnosis, and were treated according to Dutch Childhood Leukemia Study Group protocols (70%) or institutional protocols (30%), all including cranial irradiation for CNS prophylaxis. Data on late events (relapses, death in complete remission, and second malignancies) were collected prospectively after treatment; late side effects were retrospectively collected by a questionnaire, completed by the responsible pediatrician. The event-free survival of the 6-y survivors at 15 y after diagnosis was 92% (+/- 2%). Eight late relapses and nine second malignancies were diagnosed, two children died in first complete remission of late toxicity of treatment, and one child died in a car accident. The most important long-term side effects reported were learning disabilities (50%), short stature, obesity, and delayed pubertal development. No increase in the incidence of cardiovascular, pulmonary, urogenital, or gastrointestinal tract diseases or an increased vulnerability of the musculoskeletal system was found. However, prolonged follow-up is necessary to study the full-scale late effects of cytostatic treatment and radiotherapy administered during childhood.
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PMID:Late effects among long-term survivors of childhood acute leukemia in The Netherlands: a Dutch Childhood Leukemia Study Group Report. 855 52

Serum leptin levels are elevated in subjects with exogenous obesity, indicating that obesity is associated with leptin resistance. Since in man no abnormalities have yet been found in either the genes for leptin or its receptor, the mechanism of leptin resistance in obesity remains unknown. To determine if resistance might be related to leptin binding by a serum component, we assessed the carrier status of leptin in serum. The presence of a specific leptin binding factor in human serum has been established by (1) demonstrating [125I]-leptin binding to a serum component that is saturable and specifically displaceable only by unlabeled leptin and not by human growth hormone, pork insulin, insulin-like growth factors I and II, luteinizing or follicle stimulating hormones, transforming growth factor-beta 1, interleukin-6, or leukemia inhibiting factor; (2) fractionating the leptin bound serum complex and the serum leptin binding component on a molecular sieving column revealing a mass of approximately 450 kDa; and (3) identifying an inverse correlation between the concentration of serum leptin and the quantity of the leptin binding component. It is suggested that binding of leptin by this serum component may influence the physiologic response to leptin.
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PMID:Demonstration of a leptin binding factor in human serum. 916 40

We had observed that several patients with acute promyelocytic leukemia (APL) were markedly obese. Therefore we determined the relationship between obesity and a diagnosis of APL among patients with acute myelocytic leukemia (AML). Between 1980 and 1995 we saw 1245 patients with newly-diagnosed AML of whom 120 had APL. Increasing body mass index (BMI) was strongly associated with a diagnosis of APL (P=0.0003). Like Douer et al (Blood 1996; 8: 303-313) we found APL to be more frequent in Latinos and younger patients (P < 10[-4] for both). Logistic regression indicated that increasing BMI, decreasing age, and Latino origin were each independently associated with a diagnosis of APL (multivariate P values <10[-4], <10[-4], 0.0035, respectively). Since the mean BMI in the non-APL patients (25.1) resembled that of the general US population, it appears that APL patients are 'heavy' and not that non-APL patients are 'thin'. Five of the APL patients (4.2%) had a BMI >50 (vs none of the other 1125 AML patients). Given the distribution of BMI in the general US population ages 17-74, the probability that five of 120 normal adults would have a BMI >50 is virtually nil. Excluding the five very heavy APL patients does not alter the conclusion that increasing BMI predicted for APL in patients with AML. Although the mechanism is unclear there appears to be an association between increasing BMI and a diagnosis of APL among patients with AML. There may also be an association between APL and obesity.
Leukemia 1997 Oct
PMID:Association between increased body mass index and a diagnosis of acute promyelocytic leukemia in patients with acute myeloid leukemia. 973 8

The aim of this study was to investigate growth and final height in young adults after therapy for malignant diseases. Final height and weight was studied in 50 long-term survivors (LTS) of childhood cancer (aged 17-31 years; 30 men, 20 women) 3-18 years after treatment for malignant diseases (7 acute lymphoblastic leukemia, 20 lymphoma, 8 sarcoma, 15 malignant central nervous system [CNS] tumours). None of the LTS had been treated with growth hormone (GH). A decrease in final height SDS (Standard deviation score) occurred in both LTS of malignant CNS tumours (median height SDS at diagnosis, 0.3; range, -0.9 to 2.2; median final height SDS, -1.3; range, -3.9 to 1.9; p < 0.01) and LTS of lymphoma (p < 0.05) or leukemia (p < 0.05). However, only LTS who received cranial (p < 0.05) or craniospinal (p < 0.001) irradiation (XRT) exhibited reduced final heights. LTS who had received XRT not involving the CNS or had received no XRT at all presented no reduction in final height. LTS of CNS tumours treated with high craniospinal XRT doses (24 to 56 Gy) reached lower (p < 0.01) final heights when compared with LTS of leukemia who received lower cranial XRT doses (18 to 24 Gy). Final height SDS correlated with chronological age at initiation of therapy (p < 0.05). No correlation was found between the cumulative doses of applied chemotherapeutic agents and the final height of LTS. During follow-up LTS developed an increase in weight for height index (WFH) which occurred independent of XRT. In conclusion, cranial and craniospinal XRT especially in young children with malignancies resulted in a decrease in final height SDS. As 6 of 15 LTS of malignant CNS tumours exhibited a final height SDS below -2 SD, analysis of pituitary function and substitution of GH after diagnosis of GH deficiency should be considered for these patients at a young age. Others factors not directly related to XRT are responsible for the increased risk for obesity in LTS of childhood cancer.
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PMID:Final height and weight of long-term survivors of childhood malignancies. 962 45

Children with acute lymphoblastic leukaemia (ALL) typically gain weight at excessive rates during and after therapy, and a high proportion of young adult survivors are obese. Previous studies have failed to identify the abnormalities in energy balance that predispose these children to obesity. The aim of this study was to determine the cause of excess weight gain in children treated for ALL by testing the hypothesis that energy expenditure is reduced in these patients. Twenty children [9 boys, 11 girls; mean age 10.9 (3.2) y] treated for ALL who had shown excess weight gain, but were not obese [mean body mass index SD score 0.70 (1.04)], were closely and individually matched with 20 healthy control children [9 boys, 11 girls; mean age 10.7 (3.0) y; mean body mass index SD score 0.27 (0.91)]. In each child we measured total energy expenditure by doubly-labeled water method, resting energy expenditure, energy expended on habitual physical activity, and energy intake. Total energy expenditure was significantly higher in control subjects than in patients: mean paired difference 1185 kJ/d (282 kcal/d), 95% confidence interval (CI) 218-2152. This difference was largely due to reduced energy expended on habitual physical activity in the patients. Resting energy expenditure was lower in the patients: mean paired difference 321 kJ/d (76 kcal/d), 95% CI 100-541. Energy intake was also lower in the patients: mean paired difference 1001 kJ/d (238 kcal/d), 95% CI 93-1909. Children treated for ALL are predisposed to excess weight gain, and subsequently obesity, by reduced total energy expenditure secondary to reduced habitual physical activity. Prevention of obesity in ALL should focus on modest increases in habitual physical activity, modest restriction of dietary intake, and monitoring of excess weight gain.
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PMID:Reduced energy expenditure in preobese children treated for acute lymphoblastic leukemia. 977 46

The receptor for the gene product of the obesity gene, leptin, was recently reported to be expressed on murine and human hematopoietic progenitor cells. Therefore, we studied the expression of the leptin receptor, OB-R, in normal myeloid precursors, human leukemia cell lines, and primary leukemic cells using reverse-transcriptase polymerase chain reaction. In normal hematopoiesis, OB-R was expressed in CD34(+) cells. Normal promyelocytes (CD34(-)33(+) and CD34(-)13(+)) expressed only very low levels of the short, presumably nonsignaling isoform. Both the long and short isoforms of OB-R were expressed in 10 of 22 samples from patients with newly diagnosed primary or secondary acute myeloid leukemia (AML), with a higher incidence of the long isoform in primary AML (87.6% v 28.6%; P =.01). The incidence of OB-R expression was higher in recurrent than in newly diagnosed AML (P <.001), and samples from four patients with refractory AML showed strong expression of both isoforms. Both OB-R isoforms were also expressed in newly diagnosed and recurrent acute promyelocytic leukemia cells but were essentially absent in samples of chronic or acute lymphocytic leukemia. In vitro growth of myeloid leukemic cell lines and of blasts from 14 primary AMLs demonstrated that recombinant human leptin alone induced low level proliferation, significantly (P <.05) increased proliferation induced by recombinant human granulocyte colony-stimulating factor, interleukin 3, and stem cell factor in a subset of AML and increased colony formation (P <.005). Also, leptin reduced apoptosis induced by cytokine withdrawal in MO7E and TF-1 cells. Serum leptin levels correlated only with body mass index (P <. 001) and gender (P =.03). Results confirm the reported expression of leptin receptor in normal CD34(+) cells and demonstrate the frequent expression of leptin receptors in AML blasts. While normal promyelocytes lack receptor expression, leukemic promyelocytes express both isoforms. We also demonstrate proliferative effects of leptin alone and in combination with other physiologic cytokines, and anti-apoptotic properties of leptin. These findings could have implications for the pathophysiology of AML.
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PMID:Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities. 1002 96

The prevalence of obesity in children, as in adults, is increasing dramatically. The extent to which this is due to reduced energy expenditure, increased energy intake, or both, is unclear at present. This in part reflects the limitations of existing models of the pre-obese state. In childhood acute lymphoblastic leukaemia (ALL), patients typically gain weight excessively during and after 2 years of therapy, and are at high risk of becoming obese. Previous studies have failed to identify the cause of obesity in these patients. We have tested the hypothesis that excess weight gain in ALL is due to reduced total energy expenditure (TEE), measured using the doubly-labelled water method, and have identified risk factors for excess weight gain in ALL. Pre-obese children with ALL in the dynamic phase of weight gain are less physically active than their peers, with a reduced TEE of approximately 1.2 (95% CI 0.2, 2.2) MJ/d. While other factors might contribute to excess weight gain, lifestyle (i.e. reduced habitual physical activity) plays a central role in ALL. Several considerations suggest that ALL might be a useful model of the pre-obese state: lifestyle is critical to development of obesity in ALL; ALL is relatively common; approximately 70% of patients survive; patients are readily accessible during the 2 years of therapy and beyond.
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PMID:Childhood leukaemia: a model of pre-obesity. 1046 67

The axl tyrosine kinase receptor is aberrantly expressed on myeloid cells of many individuals afflicted with chronic myelogenous leukemia (CML) and other myeloid leukemias. Although previous studies demonstrated this kinase to have oncogenic potential, it is not known whether axl actively participates in the onset and/or progression of CML. We addressed this question by generating transgenic mice possessing constitutive ectopic expression of human axl throughout cells of the myeloid hematopoietic lineage through the use of the granulocyte colony-stimulating factor (GCSF) receptor promoter. The transgenics did not exhibit hematopoietic malignancies, but did exhibit phenotypic characteristics associated with noninsulin-dependent diabetes mellitus (NIDDM) including hyperglycemia and hyperinsulinemia, severe insulin resistance, progressive obesity, hepatic lipidosis, and pancreatic islet dysplasia. The obese-diabetes phenotype was similar to that observed in the agouti and melanocortin-4(-/-) mutants, however the axl transgenics were not hyperphagic. Axl transgenic animals expressed elevated serum tumor necrosis factor (TNF)-alpha levels that were further enhanced upon in vitro lipopolysaccharide (LPS) stimulation of peripheral blood. Administration of the axl ligand, gas6, to peripheral transgenic blood samples eliminated excessive TNF-alpha production in response to LPS stimulation. As a means to better understand axl-gas6 biology, transgenic animals were produced which systemically expressed the gas6-binding axl proteolytic cleavage product. A more severe NIDDM phenotype occurred in these mice. The observed phenotypes may be related to the axl receptor or proteolytic cleavage product competing with related axl family receptors for binding of the gas6 ligand. We conclude that axl expression in myeloid cells in itself does not lead to the onset or progression of leukemia and suggest that ectopic axl expression affects endogenous modulation of TNF-alpha production indirectly resulting in the NIDDM phenotype.
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PMID:Noninsulin-dependent diabetes mellitus occurs in mice ectopically expressing the human Axl tyrosine kinase receptor. 1052 29


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