Accuracy of Equations to Predict Basal Metabolic Rate in Older Women

Objective To assess the accuracy of several published equations for predicting basal metabolic rate (BMR) in older women.

Design BMR was assessed in 116 healthy, older white women, aged 60 to 82 years, on three successive mornings by indirect calorimetry. Body composition was determined by dual energy X-ray absorptiometry or hydrostatic weighing. The measured BMRs were compared with values obtained from eight published prediction equations that used solely, or in various combinations, measures of height, weight, fat-free mass, age, and menopausal status.

Statistical analyses performed The root mean squared prediction error (RMSPE) was used to determine how accurately predicted BMR matched actual BMR for each subject. In addition, regression analysis was used to evaluate accuracy of predicted BMR vs directly measured BMR.

Results Predicted mean BMR determined using all eight equations was significantly correlated to measured BMR (P=.0001), accounting for 30% to 52% of the variance of measured BMR. When analyzed by RMSPE, however, the equations of Owen et al (1986), Fredrix et al (1990), and Harris-Benedict (1919) predicted actual BMR for each subject within an average of 116 kcal/day, and the equation of Cunningham (1980) resulted in the largest prediction error at 208 kcal/day.

Applications/conclusions The regression equations of Owen et al (1986), which used body weight, Fredrix et al (1990), which used body weight and age, and Harris-Benedict (1919), which used age, weight, and height as variables, were most accurate in predicting BMR in our sample of healthy older women. J Am Diet Assoc. 1995; 95:1387-1392.     

Stabilization of thymopentin and preservation of its pharmacological properties by 2-hydroxypropyl-β-cyclodextrin

Abstract— Thymopentin prepared in 5, 15, and 20% 2-hydroxypropyl-β-cyclodextrin (HPCD) was able to inhibit guinea-pig ileum contraction stimulated by anatoxin-a (3 × 10^?6 m ) after fourteen months of storage at room temperature. Thus, in contrast to the instability of thymopentin prepared without HPCD, the pharmacological activity was retained and could be stored in a ready-to-use solution for extended periods without refrigeration.     

Suppression of Humoral Immune Responses by Dialkylnitrosamines: Structure-Activity Relationships

Suppression of Humoral Immune Responses by Dialkylnitrosamines:Structure-Activity Relationships. KAMINSKI, N. E., JORDAN, S.D., PAGE, D., KIM, B. S., AND HOLSAPPLE, M. P. (1989). Fundam.Appl Toxicol 12,321-332. Comparisons between chemical structureof N, N-dialkylnitrosamine congeners and their ability to alterthe Day 4 IgM antibody response to sRBC, body weights. and organweights of female B6C3F1 mice were investigated. Short-chainnitrosamine congeners were selected for these studies on thebasis of two criteria: (1) congeners wth symmetrical aliphaticchain length [N-nitrosodimethylamine (DMN), N-nitrosodiethylamine(DEN), N-nitrdipropylamine (DPN), N-nitrosodibutylamine (DBN)]and (2) congeners possessing an N-methyl group [N-nitrosomethylethylamine(MEN), N-nitrosomethylpropylamine (MPN), and N-nitrosomethylbutylamine(MBN)]. The immunotoxicity of each congener was evaluated basedon the compound's ability to suppress the in vivo sRBC antibodyresponse following 7 consecutive days of treatment. An ED50dose was calculated, using a linear regression analysis, foreach congener and represents the millimoles of congener perkilogram body weight required to cause a 50% suppression ofthe sRBC response. These studies demonstrated two general trends:(1) those dialkylnitrosamine congeners that possessed an N-methylgroup were most immunotoxic and exhibited comparable ED50 concentrations(42-183 µmol/kg); and (2) dialkylnitrosamine congenerspossessing symmetrical aliphatic chains demonstrated an inverserelationship between aliphatic chain length and immunotoxicpotency—DMN (62 µmol/kg) > DEN (276 µmol/kg)> DPN (467 µmol/kg) > DMN (1557 µmol/kg).Comparisons were also made between the immunotoxic potency ofvarious nitrosamine congeners in the whole animal and theirpotency in an in vitro hepatocyte-spleen cell coculture system.     

Acute Inhalation Toxicity of Aliphatic (C1-C5) Nitrites in Rats

Acute Inhalation Toxicity of Aliphatic (C₁–C₅) Nitritesin Rats. KLONNE, D. R., ULRICH, C. E., WEISSMANN, J., and MORGAN,A. K. (1987). Fundam. Appl. Toxicol. 8, 101–106. The 4-hrinhalation LC50 was determined for methyl-, ethyl-, n-propyl-,n-butyl-, isobutyl-, and isopentyl nitrite in Sprague-Dawleyrats. LC50 values were 176, 160, 300, 420, 777, and 716 ppm,respectively. The dose-mortality curves were characterized byextremely steep slopes. Toxic signs observed during exposureincluded cyanosis, prostration, and rarely, convulsions. Therewere no effects of exposure on body weight gain during a 14-daypostexposure observation period. Signs of pulmonary hemorrhagewere apparent in rats which died during exposure but were muchless prominent in rats sacrificed at study termination. No animalsdied after cessation of exposure, and rapid recovery was apparentafter exposure. Concentration x Time (CT) relationships suggestedthat the actual concentration was more important than the "dose"in determining the lethal effects of inhalation exposure tonitrites. Because of the extremely steep dose-mortality curves,the aliphatic nitrites are more hazardous than the LC50 valueswould indicate.     

Immunotoxicological Profile of Morphine Sulfate in B6C3F1 Female Mice

This study was undertaken to investigate a number of immuneparameters which may be compromised with exposure to morphinesulfate. Mice were implanted subcutaneously with 8-, 25-, or75-mg morphine sulfate pellets. Placebo pellets of identicalmakeup to the 75-mg morphine pellet (without morphine of course)were used as a control. Twenty-four hours after implantationof a 75-mg morphine pellet, blood levels reached a peak of 1610ng/ml. Corticosterone increased in parallel with morphine andreached a peak level of 966 ng/ml 24 hr after implantation.The dose response of morphine to increase corticosterone, however,was fiat. The weight of the lymphoid organs, spleen and thymus,and the liver were significantly reduced in the morphine-treatedgroups. Morphine treatment was associated with an increase inserum albumin, SGPT, BUN, and alkaline phosphatase indicativeof hepatic damage. In contrast to increased serum proteins,the C3 component of complement was reduced in a dose-dependentmanner. Leukocyte number in the peripheral blood was significantlyreduced, while erythro-cyte number and hematocrit were bothincreased. The number of B cells and T cells was decreased inmorphine-treated animals. However, the percentage of T cellsrelative to B cells was increased. The primary IgM antibodyresponse to the T-depen-dent antigen, sheep red blood cells,was decreased. Natural killer cell activity was reduced in responseto morphine, as was the phagocytic capacity of Kupffer cells.Host-resistance models of Listeria monocytogenes or Streptococcuspneumoniae showed an increased resistance following administrationof morphine. This increased host resistance, however, was notdue to an increase in antimicrobial action of sera obtainedfrom mice treated with morphine. The majority of morphine'seffects on the immune system exhibited a flat dose response,suggesting that these effects may be mediated secondarily throughcorticosterone.     

Dose-Dependent Carcinogenicity and Frequent Ki-ras Proto-oncogene Activation by Dietary N-Nitrosodiethylamine in Rainbow Trout

While the experimental data upon which current concepts in mechanisticallybased risk assessment and molecular epidemiology are groundedderive almost entirely from rodent models, fish models haveseveral attributes (e.g., low background incidence, extremelylow cost tumor studies, nonmammalian comparative status forextrapolation of mechanisms to humans) that make them valuableadjuncts for addressing these concepts. This report providesan initial characterization of the dose dependency of dietaryN-nitrosodiethylamine (DEN) hepatocarcinogenicity in Shastastrain rainbow trout (Oncorhynchus mykiss) and the potentialof DEN to elicit ras proto-oncogene activation in this species.Carcinogen was administered in the diet at five concentrationsfor 12 months. Necropsies were per formed at 9, 12, and 18 months,the latter on fish maintained on control diet for 6 months aftercessation of DEN exposure. The incidence of hepatic neoplasmsat the lower dietary concentrations (70 ppm) did not consistentlyexceed that for control groups, which were higher in this particularstudy (2%) than expected (historically 0.1%). For the higherDEN concentrations, a linear relationship between the hepatictumor incidence (expressed as log odds, log [p/(1-p)1, wherep = proportion of fish bearing tumors), and the logarithm oftotal cumulative dose was observed, with response being independentof the length of time (9 or 12 months) during which the dosewas accumulated. The dose-response curve for fish maintainedan additional 6 months postexposure was shifted toward higherincidence but was parallel to the curve for fish killed at cessationof exposure. The model predicts that doubling the dose willproduce some what more than a doubling of the odds (pl(100 -p) for tumor incidence and that the odds for lesions 6 monthspostexposure will be approximately double those at cessationof exposure. Comparison of these results with previous studiesusing rats suggests an overall similarity in dose-response curves,with trout being somewhat less sensitive than rats to DEN hepatocarcinogenesis. To examine the molecular basis for DEN carcinogenesis in this species, seven liver tumors induced separatelyby short-term DEN treatment were probed by 3'-mismatch primerpolymerase chain reaction analysis for evidence of Ki-ras proto-oncogeneactivating point mutations. A very high proportion (6/7) oftumors was found to carry codon 12 GGA - AGA mutations, whereasno codon 61 mutants were detected in this sample. These initialresults differ from those reported using hepatic tumors fromDEN-treated mice, which exhibit frequent Ha-ras codon 61 mutations[Richardson et al., Carcinogenesis 13, 1277–1279 (1992)]and rats, which appear not to carry DEN-activated ras alleles[Bauer-Hoffman et al., Carcinogenesis 11, 1875–1877 (1990)].Thus the available oncogene data for the common carcinogen DENdo not suggest a simple, consistent oncogenic pathway or mutationalspectrum useful in the molecular epidemiology of human cancers.     

Comparison of Complete and Incomplete Revascularization by Coronary Angioplasty for Unstable Angina

When a "culprit lesion" can be identified in a patient with unstable angina, it may be possible to achieve clinical improvement with incomplete revascularization. We analyzed actuarial survival free of an event (severe angina, myocardial infarction, coronary artery bypass graft, or death) at 6, 12, 18, and 24 months in 83 patients with multi-vessel disease and unstable angina who had undergone successful percutaneous transluminal coronary angioplasty (PTCA); revascularization was complete in 31 patients and incomplete in 52. Event-free survival in 85 patients with single-vessel disease and unstable angina who had undergone successful PTCA also was analyzed. Event-free survival at 24 months was worse in the multivessel disease patients than in the single-vessel disease patients (62% vs 85%; P = 0.001). Multivessel disease patients with complete revascularization had the same event-free survival as those with incomplete revascularization (63% vs 61%; P NS). Diagnostic angiograms revealed thrombus or an irregular ulcerated lesion in 42 of the multivessel disease patients. The event-free survival of these 42 patients was not different from that of the multivessel disease patients as a whole (64% vs 60%; P NS). We conclude that in patients with multivessel disease and unstable angina the event-free survival after PTCA is poorer than in patients with single-vessel disease and unstable angina. In the former patients, event-free survival does not necessarily depend on the completeness of revascularization. The outcome of patients who have intra-coronary thrombus or an irregular ulcerated lesion resembles the outcome of patients who lack these findings. (J Interven Cardiol: 1988:1:1)