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BMI from 3-6 y of age is predicted by TV viewing and physical activity, not diet.

OBJECTIVE: To investigate whether, diet, physical activity, sedentary behavior or television (TV) viewing predicted body mass index (BMI) among 3-7-y-old children. DESIGN: A triethnic cohort of 3-4-y-old children was followed for 3 y from 1986 to 1989. MEASUREMENTS: BMI was assessed at the beginning and end of each measurement year. Heart rate monitoring and observation were used to assess physical activity. Diet (calories, % calories from fat and carbohydrate), sedentary behavior and TV viewing were assessed by direct observation in each year. A repeated measures regression analysis with year as a factor and BMI at the end of each year as dependent variables was run. Nonsignificant variables were removed in a stepwise backward deletion process and significant interactions graphed. RESULTS: The interactions between minutes of TV viewing per hour and study year and minutes of physical activity per hour and study year were significant (P<0.05). There were also significant main effects for TV viewing, physical activity and BMI from the beginning of the study. The model accounted for 65% of the variance in BMI across the three study years. Plotting the significant interactions demonstrated that physical activity was positively associated with BMI in year 1, and negatively associated in years 2 and 3 with a stronger negative relationship in year 3 than 2. TV viewing became positively associated with BMI during the third study year. CONCLUSION: Physical activity and TV viewing were the only significant predictors (other than baseline BMI) of BMI among a triethnic cohort of 3-4-y-old children followed for 3 y with both physical activity (negatively associated) and TV viewing (positively associated) becoming stronger predictors as the children aged. It appears that 6 or 7 y is a critical age when TV viewing and physical activity may affect BMI. Therefore, focusing on reducing time spent watching television and increasing time spent in physical activity may be successful means of preventing obesity among this age group.

Activities of Daily Living↗

Is the current BMI obesity classification appropriate for black and white postmenopausal women?

OBJECTIVE: To evaluate the relation between body fatness (%Fat) and body mass index (BMI) and to evaluate the validity of the BMI standards for obesity established by the NIH in older black and white postmenopausal women. RESEARCH METHODS: Height, weight, BMI, and %Fat, assessed by DXA, were determined for 296 healthy, independently living women ranging in age from 50 to 80 years (M+/-s.d.; 64.4+/-7.8 years). RESULTS: Per NIH guidelines, 32% were classified as obese (> or = 30 kg/m2, mean BMI = 28.1+/-5.5 kg/m2). In contrast, using the %Fat criterion of 38% advocated by Lohman to define obesity, 47% of our sample was obese (mean %Fat=37.3+/-6.2%). A moderately high curvilinear relation existed between BMI and %Fat (R = 0.82, SEE = 3.57 %Fat, P<0.05). Race added meaningfully to the prediction of %Fat (P<0.05) such that for the same BMI, black women will have 1% lower body fatness than white women. Based on a %Fat > or = 38 as the criterion for obesity, receiver operating characteristic (ROC) analysis, performed separately by race, indicated that the currently accepted BMI cutpoint for obesity produced low sensitivity (69% and 61% for black and white women, respectively). Alternatively, BMI values > or = 28.4 kg/m2 for black women and > or = 26.9 kg/m2 for white women to define obesity maximized classification accuracy. CONCLUSION: We conclude that current BMI categories may not be appropriate for identifying obesity among postmenopausal women. Furthermore, the relation between BMI and %Fat is different in black compared to white women but remains constant from the sixth through the eighth decade of life.

Absorptiometry, Photon↗

Differences in the relationship between BMI and percentage body fat between Japanese and Australian-Caucasian young men.

This cross-sectional study aimed to determine ethnic and environmental influences on the relationship between BMI and percentage body fat, using a sample of 144 Japanese and 140 Australian-Caucasian men living in Australia, and eighty-eight Japanese men living in Japan. Body composition was assessed by anthropometry using standard international methods (International Society for the Advancement of Kinanthropometry protocol). Body density was predicted using Durnin and Womersley's (1974) equation, and percentage body fat was calculated from Siri's (1961) equation. Significant (P<0.05) ethnic differences in stature, body mass and BMI were observed between Japanese and Australian men, but no ethnic differences were observed in their percentage body fat and height-corrected sum of skinfold thicknesses. No differences were found in the BMI-percentage body fat relationship between the Japanese subjects living in Australia and in Japan. Significant (P<0.05) ethnic differences in the BMI-percentage body fat relationship observed from a comparison between pooled Japanese men (aged 18-40 years, BMI range 16.6-32.8 kg/m2) and Australians (aged 18-39 years, BMI range 16.1-31.4 kg/m2) suggest that Japanese men are likely to have a greater percentage body fat than Australian men at any given BMI value. From the analyses, the Japanese men were estimated to have an equivalent amount of body fat to the Australian men at BMI values that were about 1.5 units lower than those of the Australians (23.5 kg/m2 and 28.2 kg/m2, respectively). It was concluded that Japanese men have greater body fat deposition than Australian-Caucasians at the same BMI value. Japanese men may therefore require lower BMI cut-off points to identify obese individuals compared with Australian-Caucasian men.

Adipose Tissue↗

Changes in shape and location of BMI distributions of Swedish children.

AIMS: One aim was to disentangle how the shape and location of the BMI distribution changed among Swedish children over a 12 y period. Another aim was to identify the age during childhood when changes occurred or became manifest. METHODS: Two population-based cohorts-2,591 children from Stockholm born 1985-1987 and 3,650 from Gothenburg born 1973-1975-were compared with respect to BMI distributions from 2 to 15 y of age. RESULTS: Differences between the BMI distributions of the two cohorts were present from 5-6 y of age. From age 7, the children born in 1985-1987 and belonging to the upper parts of the BMI distribution, e.g. those above the 90th or 95th BMI percentiles, had much higher BMI mean values compared to their counterparts born 12 y earlier. Comparisons with respect to the 5th, 10th, 25th, 50th, 75th, 90th and 95th BMI percentiles showed that changes appeared above the 25th percentile and became increasingly pronounced in the upper parts of the BMI distributions. CONCLUSION: School-aged children in the rightmost parts of the BMI distributions may be more susceptible to "obesogenic" environmental exposures than those in the middle or leftmost parts. The results support the suggestion that the period of BMI rebound is critical for the development of obesity.

Adolescent↗

The activity of BMY 28142 a new broad spectrum beta-lactamase stable cephalosporin.

The in-vitro activity of BMY 28142, an iminomethoxy, aminothiazolyl cephalosporin containing a methyl pyrrolidinio C-3 was compared with that of cefotaxime, ceftazidime, aztreonam, imipenem and tobramycin against various bacteria. BMY 28142 was the most active agent tested against the Enterobacteriaceae inhibiting 90% at less than or equal to 1 mg/l. The in-vitro activity of BMY 28142 was equal to or superior to cefotaxime against the highly susceptible members of the Enterobacteriaceae and several-fold superior to ceftazidime and aztreonam. BMY 28142 inhibited many Enterobacter cloacae, Citrobacter freundii and Serratia marcescens resistant to cefotaxime, ceftazidime and aztreonam. BMY 28142 was more active than imipenem against Proteus, Providencia and Morganella species. Ceftazidime and imipenem were more active than BMY 28142 against Pseudomonas aeruginosa, but it inhibited piperacillin and tobramycin-resistant isolates. BMY 28142 inhibited beta-lactamase producing Haemophilus influenzae and Neisseria gonorrhoeae. BMY 28142 was more active than ceftazidime against streptococcal and staphylococcal species, but it did not inhibit or kill most methicillin-resistant Staphylococcus aureus. BMY 28142 did not inhibit most Bacteroides species. BMY 28142 was not hydrolyzed by common plasmid and chromosomal beta-lactamases, but it bound poorly to Enterobacter beta-lactamase, was a poor inhibitor of the TEM plasmid beta-lactamase and was a poor inducer of beta-lactamases.

Anti-Bacterial Agents↗

Bmi-1 is a novel molecular marker of nasopharyngeal carcinoma progression and immortalizes primary human nasopharyngeal epithelial cells.

The Bmi-1 oncoprotein regulates proliferation and oncogenesis in human cells. Its overexpression leads to senescence bypass in human fibroblasts and immortalization of human mammary epithelial cells. In this study, we report that compared with normal nasopharyngeal epithelial cells (NPEC), Bmi-1 is overexpressed in nasopharyngeal carcinoma cell lines. Importantly, Bmi-1 was also found to be overexpressed in 29 of 75 nasopharyngeal carcinoma tumors (38.7%) by immunohistochemical analysis. In contrast to nasopharyngeal carcinoma, there was no detectable expression of Bmi-1 in noncancerous nasopharyngeal epithelium. Moreover, high Bmi-1 expression positively correlated with poor prognosis of nasopharyngeal carcinoma patients. We also report that the overexpression of Bmi-1 leads to bypass of senescence and immortalization of NPECs, which normally express p16(INK4a) and exhibit finite replicative life span. Overexpression of Bmi-1 in NPECs led to the induction of human telomerase reverse transcriptase activity and reduction of p16(INK4a) expression. Mutational analysis of Bmi-1 showed that both RING finger and helix-turn-helix domains of it are required for immortalization of NPECs. Our findings suggest that Bmi-1 plays an important role in the development and progression of nasopharyngeal carcinoma, and that Bmi-1 is a valuable marker for assessing the prognosis of nasopharyngeal carcinoma patients. Furthermore, this study provides the first cellular proto-oncogene immortalized nasopharyngeal epithelial cell line, which may serve as a cell model system for studying the mechanisms involved in the tumorigenesis of nasopharyngeal carcinoma.

Biomarkers, Tumor↗

Efficacy and safety of BMY 21,502 in Alzheimer disease.

OBJECTIVE: To assess the efficacy and safety of BMY 21,502, a nootropic agent, in patients with mild-to-moderate Alzheimer disease. DESIGN AND PARTICIPANTS: Sixty-nine patients with Alzheimer disease (28 men, 41 women, mean age 72 y, range 54-92, mean Mini-Mental State Examination (MMSE) score 23.5) were randomized to receive either BMY 21,502 (n = 34) or placebo (n = 35) for 12 weeks of double-blind treatment followed by a 4-week placebo washout period. SETTING: Outpatient research facility. MEASUREMENTS: Primary efficacy assessments were the Alzheimer's Disease Assessment Scale (ADAS) and the Clinical Global Impressions Scale. The Computerized Neurological Test Battery and MMSE were performed as secondary efficacy measurements. RESULTS: Although overall effects were not statistically significant (p > 0.05), patients taking BMY 21,502 showed a mean change in the ADAS cognitive score of -1.5 points at week 12, compared with -0.5 in patients who received placebo. Patients with moderate dementia (MMSE < or = 20) showed a greater change at week 12 with BMY 21,502 (-2.7 points) compared with placebo (+0.3 points), but the difference was not statistically significant. Although BMY 21,502 was well tolerated in general, patients treated with BMY 21,502 experienced higher rates of abnormal liver enzyme concentrations and nausea than did those in the placebo group. There was also a higher rate of discontinuations in the BMY 21,502 group, with 12 of 34 (35%) patients in the BMY 21,502 group discontinuing, compared with 3 of 35 (9%) in the placebo group (p < 0.05). CONCLUSIONS: In this pilot study, BMY 21,502 was not found to be significantly superior to placebo during the treatment period. The compound was generally well tolerated, although 8 of 34 (24%) patients discontinued active drug treatment. Further evaluation of BMY 21,502 in a larger study population may be warranted.

Aged↗

BMI and oral glucocorticoids as predictors of prognosis in COPD patients on long-term oxygen therapy.

AIMS: The objectives of the study were to determine whether body mass index (BMI), and oral corticosteroid use predict survival and hospitalization in hypoxaemic chronic obstructive pulmonary disease (COPD) patients. METHODS: The study was a prospective cohort study with analysis of a nationwide database (Danish Oxygen Register). We studied survival and hospitalization in 221 hypoxaemic COPD patients who were on long-term oxygen therapy (LTOT). RESULTS: Low BMI was strongly associated with high mortality (P < 0.001). Maintenance treatment with steroids was only associated with higher mortality in overweight patients (BMI > or = 25 kg/m2), RR = 3.8 (1.4-10.5), P = 0.011. Whereas BMI had no influence on risk of any hospitalization in patients using oral steroids, high BMI was independently associated with reduced risk of any hospitalization in patients without oral steroids [the RR of any hospitalization for each 1 kg/m2 increase in BMI was 0.94 (CI: 0.90-0.99), P = 0.009]. Overall, the use of oral steroids was associated with increased risk of any hospitalization, RR = 1.7 (1.2-2.4), P = 0.002. This increase was especially pronounced in the group with BMI above 25 kg/m2, where steroid treatment increased the risk of any hospitalization with RR = 3.6 (1.5-8.7), P = 0.005. CONCLUSIONS: In hypoxaemic patients on LTOT, low BMI is an independent risk factor of death and any hospitalization. Maintenance treatment with oral corticosteroids is associated with increased mortality and hospitalization in COPD patients with high BMI. Our findings suggest that loss of body weight should be avoided, and that oral corticosteroids should be used cautiously in patients on LTOT--especially those with high BMI. Further research on the role of changes in body composition as a prognostic factor is needed.

Administration, Oral↗

Short-term results of laparoscopic gastric bypass in patients with BMI > or = 60.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) has been shown to be safe and effective. Little information is available about the subgroup of patients with BMI > or = 60. The goal of this study was to evaluate the feasibility and safety of LRYGBP for patients with BMI > or = 60. METHODS: The study consisted of the first 300 attempted LRYGBPs performed by one surgeon (HJS). This population was analyzed as 2 groups of patients: those with BMI < 60 and those with BMI > or = 60. Outcome variables included mortality, complications, conversion, and operative time. RESULTS: Of the first 300 LRYGBP patients, 261 had BMI < 60 and 39 had BMI > or = 60. Age, comorbidity rate, and gender distribution were similar in both BMI groups. Conversion rates were < 3% in both groups. Mean operative time for the BMI > or = 60 group was 156 minutes vs 139 minutes in the lighter group (P = 0.04). Major complications occurred more commonly in the BMI > or = 60 group (10% vs 6%) but this difference was not significant. The types of complications differed between the 2 groups, with infectious complications and gastrointestinal leak occurring more frequently in the heavier group. The mortality rate was higher in the heavier group (5% vs 0.4%, P = 0.055). CONCLUSION: LRYGBP is feasible for patients with BMI > or = 60. Our data suggest that these patients are at a higher risk for GI leak, postoperative infection, and death.

Adult↗

Parental obesity and higher pre-intervention BMI reduce the likelihood of a multidisciplinary childhood obesity program to succeed--a clinical observation.

OBJECTIVE: To assess the effects and identify factors associated with success of a combined, structured multidisciplinary weight management program in obese children and adolescents. METHODS: Seventy-seven obese children (age 6-16 years) participated in a 12-month combined dietary-behavioral-exercise intervention. Thirty-seven (age and maturity comparable) obese children who did not participate in the structured program served as controls. Body weight, BMI, and BMI percentiles were measured at baseline, after 6 months, and at the end of the intervention. RESULTS: The combined intervention was associated with a significant decrease in BMI (from 25.9+/-0.4 to 24.5+/-0.4 kg/m2, p <0.0005) and BMI percentile (from 97.3+/-0.2% to 92.6+/-0.9%, p <0.0005). In contrast, obese children who did not participate in the structured program gained weight (from 51.4+/-3.6 to 57.7+/-3.7 kg, p <0.0005), increased their BMI (from 25.2+/-1.0 to 26.6+/-0.9 kg/m2, p <0.0005), and had a non-significant increase in BMI percentiles (from 94.9+/-0.8% to 95.4+/-0.9%, NS). Children with higher BMI percentiles and parental overweight tended to respond less favorably to the combined multidisciplinary program (p <0.01). CONCLUSIONS: A prolonged (12 mo), combined, structured multidisciplinary intervention for childhood obesity resulted in a significant decrease in BMI and BMI percentiles. Higher pre-intervention BMI percentiles and parental obesity were associated with less favorable responses to the combined intervention.

Adolescent↗

Report on childhood obesity in China (2). Verification of BMI classification reference for overweight and obesity in Chinese children and adolescents.

OBJECTIVE: To verify Working Group for Obesity in China (WGOC) recommended body mass index (BMI) classification reference for overweight and obesity in Chinese children and adolescents using the data of 2002 China Nationwide Nutrition and Health Survey. METHODS: Pediatric metabolic syndrome (MetS) and abnormality of each risk factor for MetS were defined using the criteria for US adolescents. Definition of hyper-TC, LDL, and dyslipidemia in adults was applied as well. The average level and abnormality rate of the metabolic indicators were described by BMI percentiles and compared with general linear model analysis. Receiver operating characteristic analysis was used to summarize the potential of BMI to discriminate between the presence and absence of the abnormality of these indicators. RESULTS: There was neither significantly increasing nor significantly decreasing trend of biochemical parameter levels in low BMI percentile range (<65th). Slight increasing trend from the 75th and a significant increase were found when BMI > or =85th percentile. In general, the prevalence of the examined risk factors varied slightly when BMI percentile<75th, and substantial increases were consistently seen when BMI percentile > or =75th. As an indicator of hyper-TG, hypertension and MetS, the sensitivity and specificity were equal at the point of BMI<75th percentile, and the Youden's index of risk factors also reached peak point before 75th percentile except for MetS. When the BMI percentile was used as the screening indicator of MetS, Youden's index reached peak point at 85th percentile, just the point in the ROC graph that was nearest to the upper left corner. CONCLUSION: The BMI classification reference for overweight and obesity recommended by WGOC is rational to predict and prevent health risks in Chinese children and adolescents. Lower screening cut-off points, such as 83th percentile or 80th percentile, should not be excluded when they are considered as overweight criteria in future intervention or prevention studies.

Adolescent↗

BMY-14802, a sigma ligand and potential antipsychotic drug, reverses amphetamine-induced changes in neostriatal single-unit activity in freely moving rats.

The effects of BMY-14802 (5, 10, or 20 mg/kg), a sigma-receptor ligand showing preclinical evidence of antipsychotic efficacy, were tested on single-unit activity in the neostriatum of freely moving rats with or without pretreatment with 1.0 mg/kg D-amphetamine. Relative to resting baseline, amphetamine activated the large majority of neurons that changed firing rate in close temporal association with movement. All doses of BMY-14802 reversed this neuronal response, but the effect was most pronounced at 20 mg/kg. This dose, however, was equally likely to reverse or to induce a haloperidol-like potentiation of those neurons inhibited by amphetamine. In contrast, 10 mg/kg BMY-14802 consistently reversed amphetamine-induced neuronal inhibitions. All doses of BMY-14802 attenuated the locomotor effects of amphetamine, but only the higher doses also blocked other aspects of the amphetamine behavioral response. By itself, BMY-14802 dose dependently inhibited motor-related neurons, but elicited less behavioral activation than amphetamine. BMY-14802 (20 mg/kg) also induced hindlimb ataxia and occasional backwards locomotion. Haloperidol (1.0 mg/kg) reliably suppressed both behavior and neuronal activity when injected 30 min after BMY-14802, whether or not amphetamine pretreatment was given. Thus, BMY-14802 shares with other neuroleptics the capacity to reverse amphetamine-induced excitations of neostriatal motor-related neurons, whereas other effects of BMY-14802 reveal some haloperidol-like actions at 20 mg/kg that do not occur at lower doses.

Amphetamine↗

Antitumor activity and toxicity in animals of N-7[2-(4-nitrophenyldithio) ethyl] mitomycin C (BMY-25067).

BMY-25067, N-7[2-(4-nitrophenyldithio)-ethyl] mitomycin C was selected from a number of disulfide derivatives of the highly active compound RR150, N-7(thioethyl) mitomycin C for further study. BMY-25067 had tumor inhibitory effects equivalent to mitomycin C (MMC) against ascitic P388 and L1210 leukemias and M109 lung carcinoma in mice with i.p. treatment. However, it demonstrated superior activity against B16 melanoma with a high percentage of cures when both tumors and drug were given i.p. Additionally, in separate tests against B16 melanoma implanted s.c. with treatment i.v., BMY-25067 was also consistently superior to MMC. This activity was observed when therapy was initiated either one day post-tumor implant or delayed until the ninth day post-tumor implant. Slight activity was seen against a line of L1210 partially resistant to MMC and none against a line of P388 completely resistant to MMC. Against s.c. M109, BMY-25067 inhibited tumor growth but did not prolong survival with the treatment schedule used. At their respective maximum non-lethal doses in mice, BMY-25067 was less neutropenic than MMC. This was confirmed in ferrets which were also examined for the compound's effects on platelets. BMY-25067 appeared to have much less effect on platelets than MMC; the nadir for BMY-25067 was 3.8 x 10(5) platelets/cmm compared to 7 x 10(4) platelets/cmm for MMC when the drugs were compared at a dose ratio of 2:1, BMY-25067:MMC (determined to represent their relative potencies). This initial evidence of superior antitumor effectiveness particularly to a solid tumor separated from site of treatment and reduced hematologic toxicity suggest that BMY-25067 may be a worthwhile candidate for clinical trial.

Animals↗

Experimental antitumor activity of BMY-28175 a new fermentation derived antitumor agent.

BMY-28175 is a novel antitumor antibiotic produced in fermentation by Actinomadura verrucosospora. The cytotoxic effects of BMY-28175 were determined using murine and human tumor cell lines in vitro. Following 72 hour exposure, the drug had IC50 values 1.5 to 13.5 ng/ml in a microtiter assay. BMY-28175 was evaluated for antitumor activity against several experimental murine and human tumor models. The drug administered ip was active against ip implanted P388 leukemia, L1210 leukemia, B16 melanoma, M109 lung carcinoma, C26 colon carcinoma, M5076 sarcoma and Lewis lung carcinoma. In addition, BMY-28175 administered iv was active against iv implanted P388 and L1210 leukemias. BMY-28175 was active against sc implanted B16 melanoma (increased lifespan and/or inhibition of primary tumor growth) in about 60% of the tests. The growth of sc implanted M109 was inhibited by BMY-28175 in a single experiment. BMY-28175 was also active against the MX-1 human mammary xenograft implanted in the subrenal capsule of nude mice. The optimal dose for BMY-28175 in these various studies ranged from 0.16 micrograms/kg per injection with consecutive daily (qd1-9) administration, to 51.2 micrograms/kg with single dose administration. The results of these studies indicate that BMY-28175 is one of the most potent antitumor agents yet observed, with a broad spectrum of activity against tumors of murine and human origin and activity against tumors located distal to the site of drug administration.

Aminoglycosides↗

Aspirin may be more effective in preventing colorectal adenomas in patients with higher BMI (United States).

Obesity is a risk factor for colon cancer, possibly due to elevated levels of circulating cytokines derived from adipose tissue. Aspirin, which may affect the levels of these cytokines, has been shown in randomized controlled trials to decrease the risk of colorectal adenomas. We hypothesized that the chemopreventive effect of aspirin might be greater in individuals with higher body mass index (BMI). Data were available from the Aspirin/Folate Polyp Prevention Study, a randomized controlled trial of aspirin and folic acid to prevent recurrent colorectal adenomas. Obesity was defined as BMI > or = 30 (kg/m2), overweight as BMI of 25-29 (kg/m2) and normal weight as BMI <25 (kg/m2). For the analysis of the effect of aspirin on the recurrence of colorectal adenoma by BMI, we computed risk ratios for aspirin versus placebo within the three BMI strata using a modified Poisson model. Overall the risk reduction of adenomas with a daily dose of 325 mg aspirin was greater among subjects with higher BMI. Among obese subjects the risk ratio (RR) for advanced adenomas compared with placebo was 0.44 (95% CI 0.17-1.10), versus RR = 1.23 (95% CI 0.55-2.77) among those with normal weight. However, 81 mg aspirin daily did not interact with BMI to modify the risk of adenomas in such a fashion. The more pronounced effect of 325 mg aspirin in individuals with higher BMI suggests a possible protective role of anti-inflammatory aspirin against increased adipose-driven cytokines among obese subjects.

Adenomatous Polyps↗

Characterization of a human bladder cancer cell line selected for resistance to BMY 25067, a novel analogue of mitomycin C.

This study describes characteristics of a human bladder cancer cell line, SCaBER/R, selected for resistance to a mitomycin C (MMC) analogue BMY 25067. The SCaBER/R cell line was isolated by repeated 24 h exposures of the parental cells to 0.09 microM BMY 25067 (IC90, 24 h drug exposure) over a period of about 180 days. Approximately 2.2-fold higher concentration of BMY 25067 was required to kill 50% of the SCaBER/R cell line compared with parental cells (p < 0.001). The IC20 and IC90 values for BMY 25067 were also significantly higher in the SCaBER/R cell line than in SCaBER. Unlike most MMC resistant cell lines, the SCaBER/R cell line displayed a marked cross-resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and lacked cross-resistance to cisplatin, doxorubicin or VP-16. The SCaBER/R cell line also displayed a marked cross-resistance to the parent drug (MMC) and BMY 25282, another analogue of MMC. NADPH cytochrome P450 reductase activity, an enzyme implicated in bio-reductive activation of MMC, did not differ significantly in these cells. DT-diaphorase activity, another MMC activation enzyme, was significantly lower in the SCaBER/R cell line when compared to the SCaBER cells. These results suggest that relatively lower sensitivity of SCaBER/R cell line to MMC and BMY 25067 may result from impaired drug activation. Cellular levels of glutathione (GSH) and GSH-transferase (GST), which have been suggested to affect the cytotoxicity of MMC, were comparable in SCaBER and SCaBER/R cell lines. BMY 25067 induced DNA interstrand cross-links (DNA-ISC) could not be detected in either of the cell lines even at drug concentrations which produced a significant cell kill. These findings suggest that (a) cellular resistance to BMY 25067 in the SCaBER/R cell line may be due to impaired drug activation, and (b) the nature of the cytotoxic produced by BMY 25067 may be different from that of MMC.

Antineoplastic Agents↗

Obstetric outcomes associated with increase in BMI category during pregnancy.

OBJECTIVE: The purpose of this study was to investigate effect of increase in body mass index (BMI) category on obstetric outcomes. STUDY DESIGN: A cohort study was conducted from 1999 to 2002. Women with singleton pregnancies were placed in standard BMI categories. Increase in BMI was calculated as difference between initial BMI and delivery BMI. ANOVA was used to compare continuous variables, and chi-square test for categorical variables. RESULTS: This study included 5131 women: 49.8% had no change in BMI category, 43.9% increased by 1 BMI category, and 6.3% by >1 category. Increase in BMI category was associated with higher rates of gestational diabetes (P = .005), failed induction (P < .001), lacerations (P < .001), cesarean deliveries (P < .001), and postpartum infection (P = .007) in normal weight women. Overweight women also had increased rates of preeclampsia (P = .002) and operative vaginal deliveries (P < .001). Obese women had higher rates of chorioamnionitis (P = .003), failed induction (P < .001), and cesarean deliveries (P = .016). CONCLUSION: Increase in BMI category is associated with increased risk of complications.

Adult↗

Expression of the p16(INK4a) gene product, methylation of the p16(INK4a) promoter region and expression of the polycomb-group gene BMI-1 in squamous cell lung carcinoma and premalignant endobronchial lesions.

It is generally assumed that squamous cell carcinoma develops in a stepwise manner from normal bronchial epithelium towards cancer by the accumulation of (epi)genetic alterations. Several mechanisms including mutations and homozygous deletions or hypermethylation of the p16(INK4a) promoter region can cause loss of p16 expression. Recent studies suggest overexpression of the polycomb-group gene BMI-1 might also down-regulate p16 expression. In this study, we analyzed the p16 expression in relation to the methylation status of the p16 promoter region of the p16(INK4a) gene and the expression of BMI-1 in bronchial squamous cell carcinomas (SCC) and its premalignant lesions. Nine (69%) SCC showed loss of p16 expression and 10 (77%) showed expression of BMI-1. Of four p16 positive samples two (50%) were BMI-1 positive, whereas among nine p16 negative samples, eight (89%) revealed BMI-1 staining. Four (44%) p16 negative samples were hypermethylated at the p16(INK4a) promoter region; the other p16 negative tumors that showed no hypermethylation revealed BMI-1 staining. Only two premalignant lesions showed absence of p16 expression, of which one (carcinoma in situ) was hypermethylated at the p16(INK4a) promoter region and the other (severe dysplasia) showed BMI-1 expression. In total, 11 precursor lesions (48%) revealed BMI-1 expression. In conclusion, the results of this study suggest that loss of p16 expression by promoter hypermethylation is inconsistently and occurs late in the carcinogenic process at the level of severe dysplasia. To what extent overexpression of the polycomb-group protein BMI-1 attributes to down regulating of p16 expression remains unclear.

Aged↗