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PubMed2005

What is the best measure of adiposity change in growing children: BMI, BMI %, BMI z-score or BMI centile?

BACKGROUND: Weight control programs for obese children monitor change in body mass index (BMI) adjusted for age. However, change can be measured in several ways: raw (kg/m2) units, percentage, z-scores or centiles. The suitability of the different measures is not known. AIM: To identify the optimal BMI measure for change, whose short-term variability is most consistent for children across the spectrum of adiposity. SETTING: An Italian kindergarten. SUBJECTS: A total of 135 (66 female) children aged 29-68 months at baseline, with BMI measured three times over a 9-month period. METHODS: Each child's short-term variability in adiposity was summarized by the standard deviation (s.d.) of BMI and BMI % adjusted for age, and BMI z-score and BMI centile. The s.d.'s were then compared in obese and nonobese children, and also correlated with each child's baseline BMI z-score. RESULTS: The within-child s.d.s of BMI z-score and BMI centile were significantly smaller in obese than nonobese children, while the s.d.s of BMI and BMI % were similar in the two groups. Also, the within-child s.d.s of z-score and centile, and to a lesser extent BMI %, were significantly inversely correlated with baseline z-score, whereas the s.d. of BMI was not. The changes in adiposity over time, as assessed by the four measures, were very highly correlated with each other, particularly for BMI with BMI %. DISCUSSION: Even though BMI z-score is optimal for assessing adiposity on a single occasion, it is not necessarily the best scale for measuring change in adiposity, as the within-child variability over time depends on the child's level of adiposity. Better alternatives are BMI itself or BMI %. Our results underscore the importance of using a relatively stable method to assess adiposity change when following children at risk of obesity.

Adipose Tissue↗

PubMed1992

Effect of buthionine sulfoximine and ethacrynic acid on cytotoxic activity of mitomycin C analogues BMY 25282 and BMY 25067.

BMY 25282 and BMY 25067, analogues of mitomycin C (MMC), were synthesized in an attempt to increase the therapeutic potential of the parent drug. The present studies were undertaken to determine if the cytotoxicity of MMC or its analogues is affected by cellular glutathione (GSH) and/or GSH transferase (GST) levels by using sensitive (P388/S) and multidrug resistant (P388/R-84) mouse leukemia cells as a model. P388/R-84 cells were cross-resistant to all three drugs. BMY 25067 was > 100 times more cytotoxic than MMC in both the cells. MMC and BMY 25282 produced significantly lower DNA interstrand cross-links (ISC) in P388/R-84 cells, whereas BMY 25067 induced ISC formation was comparable in these cells. GSH depletion with D,L-buthionine-S,R-sulfoximine (BSO) increased sensitivity to MMC, BMY 25282, and BMY 25067 by 3.4-, 4.1-, and 1.8-fold, respectively, in the resistant cells. Pretreatment of P388/R-84 cells with a nontoxic concentration of ethacrynic acid (EA) (10 micrograms/ml for 1 h), an inhibitor of GST activity, also resulted in a significant increase in the cytotoxic activities of MMC and BMY 25282 (3.8- and 3.1-fold, respectively), but not of BMY 25067. Combined pretreatment of P388/R-84 cells with BSO and EA caused further increase in the cytotoxic activities of both MMC and BMY 25282. Potentiation of BMY 25067 cytotoxicity by combined BSO and EA pretreatments was similar to that observed by BSO pretreatment alone. The ISC formation by MMC and BMY 25282 were also increased significantly by BSO or EA pretreatment in these cells. Whereas BSO treatment increased BMY 25067 induced ISC formation, it was not affected by EA pretreatment. These results suggest that (a) a potentiation of the cytotoxic activity of MMC or BMY 25282 can be achieved by GSH depletion and/or GST inhibition, (b) the enhanced cytotoxicity may be caused at least in part by the increased formation of drug-DNA cross-links, and (c) the mechanism of BMY 25067 cytotoxicity may be different from the other two drugs. The results of the present study also suggest that BMY 25067 may be seriously considered for further clinical development because it is much more active than MMC, and unlike the parent drug cytotoxicity of BMY 25067 does not seem to be affected by GST levels, which have been suggested to play an important role in cellular resistance to several cancer chemotherapy drugs.

Animals↗

PubMed1993

Contrasting molecular cytotoxic mechanisms of mitomycin C and its two analogs, BMY 25282 and BMY 25067, in isolated rat hepatocytes.

The molecular cytotoxic mechanisms of mitomycin C (MMC) and its analogs, BMY 25282 and BMY 25067, have been investigated using isolated hepatocytes as a model system for studying toxicity to nondividing tissues. These drugs have quinone and aziridine moieties, and tumor cell cytotoxicity has been attributed to DNA alkylation and cross-linking. By contrast, the following results suggest that these drugs cause oxidative stress in nondividing cells by different mechanisms. Both hepatocytes or hepatic microsomes and NADPH were able to catalyse oxygen activation by all three drugs, suggesting that enzymatic reduction results in the formation of auto-oxidizable species. Their relative effectiveness at activating oxygen was BMY 25282 >> BMY 25067 > MMC. However, their relative cytotoxic effectiveness was BMY 25067 >> BMY 25282 > MMC, and it was increased markedly if hepatocyte glutathione-reductase or catalase was inactivated. Furthermore, ascorbate increased the toxic potencies of both BMY 25282 and MMC in catalase-inactivated hepatocytes by as much as 60- and 40-fold, respectively. Hepatocyte glutathione (GSH) oxidation was also increased. The relative resistance of normal hepatocytes to MMC and BMY 25282 can be attributed therefore, to the high levels of enzymes in hepatocytes involved in hydrogen peroxide detoxification. BMY 25067 cytotoxicity unlike that of BMY 25282 or MMC was prevented by the addition of the thiol reductant dithiothreitol. BMY 25067 also differed in being much more toxic towards GSH-depleted hepatocytes. Furthermore, BMY 25067, unlike MMC and BMY 25282, caused a rapid decrease in hepatocyte ATP levels and inhibited mitochondrial respiration. This could be prevented by the addition of the thiol reductant dithiothreitol, which restored intracellular GSH levels. Its toxic potency to catalase- or glutathione reductase-inactivated hepatocytes also was not increased by ascorbate. Therefore, the cytotoxicity of BMY 25067 can probably be attributed to oxidative stress by the aminodisulfide moiety which causes GSH and mixed disulfide formation, resulting in mitochondrial toxicity.

Adenosine Triphosphate↗

PubMed1986

Effects of tiaspirone (BMY-13859) and a chemical congener (BMY-13980) on A9 and A10 dopamine neurons in the rat.

Two new potential antipsychotic drugs, BMY-13980 and BMY-13859 were compared for the ability to influence the electrophysiological activity of dopaminergic neurons in the substantia nigra zona compacta (A9 DA cells) and ventral tegmental area (A10 DA cells) in the brain of the rat. Both drugs reversed the rate-suppressant effects of the DA agonist apomorphine on DA cells in A10 to a greater extent than DA cells in A9; BMY-13980 was particularly selective in this regard. These results indicate that both drugs may exert DA antagonist effects which are suggestive of antipsychotic potential. In other experiments, the effects of chronic (28 days) treatment with BMY-13980 and BMY-13859 on the neuronal activity of DA were evaluated. Both compounds caused a significant decrease in the number of spontaneously active DA neurons in A10 recorded per electrode track, an effect previously demonstrated to be associated with antipsychotic efficacy. The drug BMY-13859, but not BMY-13980, also significantly decreased the number of spontaneously active DA cells/track in A9, an effect which may predict the liability of potential antipsychotic drugs for causing extrapyramidal motor dysfunction, including tardive dyskinesia. Thus, these experiments indicate that both BMY-13980 and BMY-13859 exert effects which may predict potential antipsychotic efficacy in clinical trials and that BMY-13980 may be less likely to cause extrapyramidal side effects.

Animals↗

PubMedDate not supplied

Body Mass Index (BMI), BMI change and mortality in community-dwelling seniors without dementia.

UNLABELLED: Recently Canada adopted the World Health Organization's (WHO)Weight Classification system for Body Mass Index (BMI). To date, there has been minimal investigation on the predictive ability of BMI on mortality in seniors. This study investigates the predictive ability of the BMI categories identified in this Weight Classification System and change in BMI on mortality in Canadian seniors. METHODS: Canadian Study of Health and Aging (CSHA) participants who completed clinical examination (including body weight measurements) in 1991 (CSHA1) and 1996 (CSHA2) were included (n = 539). BMI change (CSHA1 to CSHA2) was categorized as no change/mild increase (0 to < 2.0 units), mild decrease (-0.1 to < -2.0 units), or significant increase/decrease (> or = +/-2.0 units). The outcome was subsequent 5-year-mortality, i.e. death between CSHA2 and CSHA3 (2001). Logistic regression controlled for age, gender, education level, marital status, smoking and cognitive status. RESULTS: BMI at CSHA1 was not a significant predictor of all-cause mortality between CSHA2 and CSHA3. A significant decrease in BMI regardless of BMI category predicted death (OR 2.10 95% CI 1.17, 3.80). Other factors predictive of death were age and cognitive impairment without dementia. CONCLUSION: A static measure of BMI is a less useful measure of mortality risk than weight change in older adults. Weight change, especially weight loss resulting in a BMI change of at least 2.0 units, is predictive of mortality and should be considered a warning sign.

Aged↗

PubMed2001

[Body mass index (BMI) and percent fat mass. A BMI > 27.5 kg/m2 could be indicative of obesity in the Spanish population].

BACKGROUND: The World Health Organization (WHO) defines obesity as a condition of excessive fat accumulation to the extent that health and well-being are affected. For population studies, the measurement of weight, corrected for height, is still the method of choice (BMI). In Caucasian populations, the BMI cut-off point for obesity (30 kg/m2) corresponds with a percent body fat (PFM) of over 25% in young adult males and 35% in young adult females. However, the relation between BMI and PFM is not uniform among populations. It is important to define in each population the threshold of BMI which corresponds to the definition of obesity. PATIENTS AND METHOD: BMI was calculated in 282 subjects. PFM was analyzed using Bio-electrical impedance. Blood pressure, serum glucose and insulin, and the fasting insulin resistance index were also determined in all subjects to analyze the metabolic impact. RESULTS: The PFM of 25% in males and 35% in females corresponded to a BMI of 27.5 and 27.4 kg/m2, respectively. The slope of the relationship between the degree of obesity and comorbilities (insulinemia, fasting insulin resistance index and blood pressure) was strengthened above 26 kg/m2 in men and 24 kg/m2 in women. CONCLUSIONS: BMI that corresponds to a PFM previously defined as obesity is lower in our population in comparison with other Caucasian populations. Our results confirm that is impossible to compare the prevalence of obesity among populations using exclusively the BMI. It will be important to define, using reference methods, whether these findings have physiological impact or not, and if this cut-off of BMI determines an increment in cardiovascular and overall mortality using epidemiological approaches.

Adipose Tissue↗

PubMed2006

Adiposity in adolescents: change in actual BMI works better than change in BMI z score for longitudinal studies.

PURPOSE: Longitudinal epidemiologic studies often relate adiposity changes to suspected causal factors. In growing adolescents, this becomes complicated. Many investigators use within-child change in body mass index (BMI) z scores (Delta z) from sex- and age-specific BMI charts developed by the Centers for Disease Control and Prevention (CDC). These charts, derived from cross-sectional data, may not represent BMI growth patterns of real children. Furthermore, because cross-sectional BMIs are not Gaussian, these z scores are from month-specific transformed distributions, with possible unintended consequences when used longitudinally. Alternatively, we can directly analyze BMI change (Delta BMI). We compare these two widely used measures of change in adiposity. METHODS AND RESULTS: With real adolescent data, we show that annual Delta BMIs have nonlinear peaks that are inconsistent with the CDC curves. We also show that a specified Delta z represents a broad range of adiposity changes for children measured at the same two ages. To see how this affects power, we performed simulation studies confirming that analyzing Delta BMIs in models with hypothesized factors is more powerful than analyzing Delta zs. CONCLUSIONS: In longitudinal studies of adolescent adiposity, investigators should be encouraged to analyze Delta BMI rather than Delta z because analyses using BMI are more powerful and findings presented in BMI units are more interpretable.

Adipose Tissue↗

PubMed2003

Identifying adolescents with high percentage body fat: a comparison of BMI cutoffs using age and stage of pubertal development compared with BMI cutoffs using age alone.

OBJECTIVE: To ascertain whether body mass index (BMI) cutoffs calculated according to age and pubertal stage are superior to BMI cutoffs calculated on the basis of age alone at correctly identifying children and adolescents with high levels of adiposity. DESIGN: Cross-sectional study. SETTING: Dunedin, a university city in New Zealand. SUBJECTS AND MEASUREMENTS: In total, 368 healthy Caucasian children and adolescents (179 males, 189 females) aged 8.5-15.5 y had their percentage body fat measured by dual-energy X-ray absorptiometry (DXA). High adiposity was defined as > or =25% body fat in males and > or =35% body fat in females. The sensitivity, specificity and areas under the receiver operating characteristic curves of two Z-score distributions of BMI were calculated for each gender. RESULTS: Forty-nine males (27.3%) and 43 females (22.8%) had high DXA-measured percentage body fat. In all, 86% of males and females with high adiposity were correctly identified by BMI cutoffs calculated according to age alone, with 89% of males and 97% of females with low adiposity being correctly classified. Similar results were observed when BMI cutoffs utilising both age and stage of pubertal development were used; 90% of males and 88% of females with high adiposity and 92% of both males and females with low adiposity were correctly classified according to BMI. CONCLUSIONS: Categorisation of BMI according to both age and pubertal stage of development does not produce cutoffs that are superior to BMI cutoffs calculated on the basis of age alone at identifying children with high DXA-measured adiposity. SPONSORSHIP: University of Otago and the Health Research Council, New Zealand.

Absorptiometry, Photon↗

PubMed1995

Relationship of serum alanine aminotransferase (ALT) to body mass index (BMI) in blood donors: the need to correct ALT for BMI in blood donor screening.

A study was carried out on 1,028 voluntary blood donors to see how body mass index (BMI) correlated with the serum alanine amino transferase (ALT) activity. The mean ALT (U/l) values were 19.35, 27.63, 40.79 and 54.41 in the four BMI categories of < or = 20, 20.1-25, 25.1-30 and > 30, respectively. This study showed that the mean serum ALT level of obese subjects (BMI > 30 kg/m2), compared with the two categories of normal subjects (i.e. BMI < or = 20 and BMI = 20.1-25 kg/m2), was increased by 2.8 and 1.96 times, respectively. Compared with the BMI group < or = 20, there was a gradual per cent increase in the mean serum ALT in the three different BMI groups: 20.1-25 (+133%), 25.1-30 (+196%) and > 30 kg/m2 (+280%). This indicates the need to correct ALT values for BMI for blood donor screening, instead of using actual ALT values.

Adult↗

PubMed2004

Correlation between fasting plasma ghrelin levels and age, body mass index (BMI), BMI percentiles, and 24-hour plasma ghrelin profiles in Prader-Willi syndrome.

Ghrelin is a GH-releasing acylated peptide found in the stomach and a centrally acting food intake stimulator. Prader-Willi syndrome (PWS) is a genetic disorder characterized by a voracious appetite and increased fasting ghrelin levels. In this report we describe 24-h ghrelin profiles in PWS children (n = 5) and compare these with age, sex, and body mass index (BMI)-matched controls (n = 5). A 3- to 4-fold increase in ghrelin levels was found in PWS over a 24-h period, compared with controls (P < 0.001). Interestingly, there was a greater tendency for the up-regulation of ghrelin level in lean PWS than in obese PWS. To confirm this finding, we measured fasting ghrelin levels in 39 patients with PWS. Inverse correlations were found between plasma ghrelin levels and the following: age (r = -0.408, P = 0.005), BMI (r = -0.341, P = 0.017), percentage of the ideal weight for age (r = -0.382, P = 0.008), and BMI percentile (r = -0.311, P = 0.027). Our data show that there may be a suppressive (or up-regulating) controlling mechanism of ghrelin secretion in obese (or lean) PWS children. We hope that our data may further explain the mechanisms underlying the insatiable appetite and obesity characteristic of PWS.

Adolescent↗

PubMedDate not supplied

In vitro activity of cefprozil (BMY 28100) and cefepime (BMY 28142) against Streptococcus pneumoniae, Branhamella catarrhalis, and Haemophilus influenzae, and provisional interpretive criteria for disk diffusion and dilution susceptibility tests with Haemophilus influenzae.

The in vitro activities of two new cephalosporins, an oral agent, cefprozil and a parenteral compound, cefepime, were assessed against recent clinical isolates of Streptococcus pneumoniae, Moraxella (Branhamella) catarrhalis, and Haemophilus influenzae. In general, both cefprozil and cefepime MICs were higher for beta-lactamase-producing strains of M. catarrhalis in comparison to strains that lacked beta-lactamase. By contrast, beta-lactamase-positive and -negative strains of H. influenzae had similar cefprozil and cefepime minimum inhibitory concentrations (MICs). The MIC90 values for cefprozil were 0.12, 32, 4.0, and 0.5 micrograms/ml versus S. pneumoniae, H. influenzae, and beta-lactamase-positive and negative strains of M. catarrhalis, respectively. In comparison to three other oral cephalosporins included in this study, cefaclor, cefuroxime axetil, and cefixime, cefprozil was the most active agent against S. pneumoniae, the least active against B. catarrhalis, and equivalent in activity to cefaclor against H. influenzae. The cefepime MIC values against S. pneumoniae, H. influenzae, and beta-lactamase-positive and negative strains of M. catarrhalis were 0.03, 0.25, 2.0, and 0.5 micrograms/ml, respectively. Cefepime was less active than ceftriaxone for all three organism groups, however, was in all cases more active than cefixime, cefuroxime, cefaclor, and cefprozil.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefepime↗

PubMed2002