Change in Nutrient Intakes, Number of Servings, and Contributions of Total Fat from Food Groups in 4- to 10-Year-Old Children Enrolled in a Nutrition Education Study

Objective To determine change in nutrient intakes, number of servings, and contributions of total fat from food groups in children who lowered their dietary fat intake.Design A research and demonstration study designed to lower plasma low-density lipoprotein cholesterol level. There were four study groups: two intervention and two control groups. All children had hypercholesterolemia except for those in one control group. Three 24-hour dietary recalls were collected on randomly assigned days over a 2-week period at baseline and 3 months after the intervention.Subjects Three hundred three 4- to 10-year old children from suburbs north of Philadelphia, Pa.Interventions One intervention involved a home-based, parent-child autotutorial program (PCAT group) with audiotaped stories and print materials for the children and their families; the other intervention involved one face-to-face counseling session with a registered dietitian (counseling group).Outcome measures Change in mean nutrient intakes compared with the Recommended Dietary Allowance (RDA); change in number of servings and mean grams of total fat contributed from 10 different food groups.Statistical analyses performed Analyses of variance and χ² analyses.Results Children in every study group had mean intakes of all nutrients (except vitamin D) greater than 67% of the RDA 3 months after the baseline measurement. Several food groups (ie, meats, dairy products, fats/oils, and desserts) provided less total fat to the diets of children who reduced their dietary lipid intake after 3 months (ie, PCAT and counseling groups). These children also reduced the mean number of servings selected from these food groups. Within these same food groups, some children consumed fewer servings of higher fat foods and more servings of lower fat foods.Applications/conclusions Children who lowered their dietary fat intake after intervention reported both quantitative and qualitative changes in food choices from several food groups. These choices did not significantly reduce their nutrient intakes. J Am Diet Assoc. 1996; 96:865-873.     

Affinity Maturation and Isotype Switch in Clonally Related Anti-Erythrocyte Autoantibodies

The NZB mouse is genetically predisposed to develop, at approximately 6 months of age, a spontaneous and severe autoimmune anaemia caused by production of pathogenic anti-mouse erythrocyte auto-antibodies. Molecular analysis of a panel of five anti-erythrocyte monoclonal antibodies (MoAb) derived from splenocytes of unimmunized NZB mice revealed that these autoantibodies all had functionally rearranged genes from the V_H J558 family of immunoglobulin genes with closest homology to germline genes H10 and H30. Owing to clustering of nucleotide differences within the CDRs, compared with the germline, it was concluded that these antibodies were most likely generated by an antigen-driven mechanism.
We report here further molecular analysis of two (4.16.1 and B4.13.2) of the panel of five anti-mouse erythrocyte producing hybridomas which are apparently clonally related. Nucleotide analysis of the light chain cDNA indicated that both antibodies had closest homology to germline gene V_k24 and use J_k2 gene. Determination of the functional affinities of the MoAb reveal that B4.13.2 (IgG2a) has a > 10-fold higher affinity for mouse erythrocytes when compared to 4.16.1 (IgGl). This finding supports the view that these two autoantibodies are generated by an antigen-driven mechanism. The proposed mechanism would involve the selection and expansion of a small population of B-lymphocytes by antigen leading to isotype switch, somatic mutation and increased affinity. Our data also point to the possibility that some framework residues may be involved in the binding to antigen.     

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.     

Retinoid-Induced Hypertriglyceridemia in Rats Is Mediated by Retinoic Acid Receptors

Retinoids in clinical use today are known to induce hypertriglyceridemiaas one of their major side effects. The purpose of the presentstudy was to determine, in an appropriate animal model, if retinoid-inducedhypertriglyceridemia is mediated by retinoic acid receptors(RARs) and/or by retinoid X receptors (RXRs). Oral gavage ofmale Fischer rats with 13-cis-retinoic acid for 6 days causeda rapid and sustained increase in serum triglycerides that wasreversible within 4 days posttreatment In subsequent experiments,rats were treated by gavage once daily for 3 days with variousretinoids, and serum triglyceride levels were determined 24hr after the last treatment without fasting. All-trans-and 13-cis-retinoicacid, which can be converted to both RAR and RXR agonists, and9-cis-retinoic acid, an RAR/RXR pan-agonist, caused dose-dependentincreases in serum triglycerides at doses that did not causeweight loss or mucocutaneous toxicity. Ro 13–6298 andAGN 190121, two RAR-specific agonists, caused dose-dependentincreases in serum triglycerides, although Ro 13–6298only induced hypertriglyceridemia at weight-suppressive doses.Two RXR-selective agonists, LG100268 and AGN 191701, failedto induce hypertriglyceridemia or weight loss up to the highestdoses tested. A structural isomer of AGN 190121 that does notactivate RARs or RXRs, AGN 190727, did not induce hypertriglyceridemia.Hypertriglyceridemia induced by AGN 190121 was significantlyinhibited by co-treatment with an RAR-selective antagonist,AGN 193109. Taken together, these data provide strong evidencethat retinoid-induced hypertriglyceridemia is mediated, at leastin part, by RARs. These data also suggest that RXR-specificagonists may have reduced potential to induce hypertriglyceridemiarelative to RAR-active retinoids.     

Developmental Toxicity of L-Selenomethionine in Macaca fascicularis

Forty pregnant long-tailed macaques were dosed via nasogastricintubation with 0, 25, 150, or 300 µg/kg of L-selenomethionine(Se) daily during organogenesis [Gestational Day (GD) 20–50].Clinical examination of the dams, maternal body weights, sonographicevaluations, clinical chemistry screens, and measures of serumprogesterone and urinary estrone conjugates were used as indicatorsof maternal and fetal status in all animals. The pregnanciesof two to three dams from each dose group were followed untilterm ({small tilde}GD 165); the remainder (N = 7/dose group)were scheduled for hysterotomy on GD 100 ± 2. A standardteratologic evaluation was performed including visceral andskeletal examinations. Fetal liver, kidney, skin, and smooth,cardiac, and skeletal muscles were examined by light microscopy;heart muscle was also evaluated by transmission electron microscopy.Neonates delivered at term remained with the dams and were removedperiodically for morphometric, neurologic, behavorial, and ophthalmologicassessments on Days 1, 8, 15, 22, and 30 of age. Dose-dependentmaternal toxicity as evidenced by anorexia, vomiting, and asignificant reduction in body weight increased with increasingduration of Se exposure. One growth-retarded fetus was recoveredon GD 131 from a compromised dam exposed to 25 /ig/kg-day; oneearly embryonic death (GD 35) and two fetal deaths [GD 68 (followedby maternal death) and GD 123] occurred among animals dosedwith 300 µg/kg-day. Pregnancy loss among treated animalswas not significantly different from concurrent or historicalcontrols. No statistically significant treatment-related effectswere observed at necropsy on GD 100 ± 2. One infant exposedto 150 Mg/kg-day prenatally exhibited a unilateral corticalcataract, which may have been a spontaneous occurrence. Thelimited developmental effects observed and reported teratogenesisin nonmammalian species suggest that comparative pharmacokineticstudies are required before the full public health significanceof elevated Se is understood.     

Chronic Marijuana Smoke Exposure in the Rhesus Monkey I. Plasma Cannabinoid and Blood Carboxyhemoglobin Concentrations and Clinical Chemistry Parameters

Chronic Marijuana Smoke Exposure in the Rhesus Monkey I. PlasmaCannabinoid and Blood Carbxyhemoglobin Concentrations and ClinicalChemistry Parameters SLIKKER, W., JR., PAULE, M. G., ALI, S.F., SCALLET, A. C., AND BAILEY, J. R (1991). Fundam. Appl Toxicol17, 321–334. This report is the first in a series abouta large multidisciplinary study designed to determine whetherchronic marijuana (MJ) smoke exposure results in residual behavioraland/or neuropathological alterations in the rhesus monkey. Priorto the initiation of a year of chronic MJ smoke exposure, 64periadolescent male rhesus monkeys were trained for 1 year toperform five operant behavioral tasks and then divided, accordingto their performance in these tasks, into four exposure groups(n=15–16/group): (1) a high dose (HI) group, exposed 7days/week to the smoke of one standard MJ cigarette; (2) a lowd m (LO) group, exposed on weekend days only to the smoke ofa standard MJ cigarate; (3) an extracted MJ cigarette (EX) group,exposed 7 days/week to the smoke of one ethanol-extracted MJcigarette; and (4) a sham group (SH), exposed 7 days/week tosham exposure conditions. Daily exposures for 1 year were accomplishedusing a mask that covered the subjects' nose and mouth. Averagebody weights (initially 3.7?0.5 kg, mean?SD) and rates of weightgain (approximately 0.1 kg/month) were the same for all groupsthroughout the entire experiment. During the first week of expsure,plasma concentrations of -9-tetrahydrocannabinol and 11-nor-9-carboxy-THCin the HI group were 59?7 (mean?SE) and 5.5?1.5 ng/ml, respectively,45 min after MJ smoke administration and did not change significantlyat similar times after exposure throughout the remainder ofthe year. Whole blood carboxyhemoglobin levels increased toapproximately 13% 1 min after expsure to smoke in either theMJ or the EX groups. Comparison of blood chemistry and hematologyvalues before, during, and after exposure indicated no differencesfor most parameters. During exposure, lymphocytes, alkalinephosphatase and -glutamyl transferase were depressed in theHI group compared to in the SH group. During exposure, aspartateaminotransferase was elevatd for both the HI and EX groups,suggesting a general effect of smoke exposure. Because theseeffects were transient and remained within the range of reportednormal values, these data indicate that long-term, experimentalexperimental exposure to MJ smoke is feasible and does not compromisethe general health of the rhesus monkey.     

Triiodothyronine (T3) and Cardiovascular Therapeutics: A Review

Hypothyroidism is associated with an abnormal hemodynamic state characterized by decreased heart rate, stroke volume, output, and contractility, and increased systemic vascular resistance. Since cardiopulmonary bypass (CPB) and surgical stress can induce profound decreases in triiodothyronine (T3) levels, the hemodynamic consequences of "stress-induced" hypothyroidism and T3 repletion are of increasing clinical interest. Available data generally support the likelihood of a beneficial effect associated with T3 replacement in brain-dead organ donors and in cases of low cardiac output following CPB. Although hypotheses have been advanced to account for these salutary effects, the mechanism by which T3 may augment hemodynamic performance has not been precisely defined, particularly in the acute setting. Although additional research is needed to clarify these and other issues, preliminary findings with T3 replacement indicate that such investigation is warranted.     

Acute tubulointerstitial nephritis,treatment with steroid and impact on renal outcomes

Background: The use and timing of steroids in the management of acute tubulointerstitial nephritis (ATIN) remains debatable. Aims: To determine the incidence and aetiology of ATIN in our unit, and to examine trends in the use of steroids and their impact on renal outcomes. Methods: Patients with a histological diagnosis of ATIN over a 9‐year period were identified and divided into steroid‐treated (StG) and steroid‐naïve groups (SnG). Mean change in estimated glomerular filtration rate (eGFR) was determined. Results: Forty‐nine patients had ATIN as their main diagnosis, 67% of cases were drug‐induced, and proton pump inhibitors (PPI) were the second commonest implicated drug category. Majority (75%) of patients received steroids, and eGFR improved to a significantly greater degree in these steroid‐treated patients (3.4‐fold improvement vs 2.0‐fold in SnG; P < 0.05, unpaired t‐test). Despite comparable eGFR at presentation (StG: 11.7; SnG: 15.4), steroid‐treated patients were less likely to receive dialysis, although not significantly so (OR 0.27; 95% CI 0.06–1.15, P = 0.066, chi‐squared test). However, there was no significant relation between the degree of eGFR improvement and delay in starting steroids (Pearson r = ?0.25, P > 0.45), and no difference in eGFR at the time of last follow‐up (StG: 33 ± 3; SnG: 32 ± 7; P > 0.9, unpaired t‐test). Conclusion: StG patients had a greater degree of improvement in renal function, but with no correlation between degree of improvement in eGFR and delay in starting steroids, and similar eGFR values at final follow‐up. PPI were the second commonest drug category among drug‐induced cases.     

Use of the Implantable Loop Recorder in Evaluation of Patients with Unexplained Syncope

Syncope is a complex symptom with multiple potential etiologies that can be difficult to establish. The major obstacles to diagnosis are the periodic and unpredictable nature of events and the high spontaneous remission rate. Short-term ECG monitoring often is unproductive when initial noninvasive testing is negative due to the low probability of recurrence during the brief monitoring period. Implantable loop recorders extend the ability to monitor cardiac patients, enhancing the diagnostic yield to as high as 85% in difficult to diagnose syncope. Several recent studies suggest that prolonged monitoring with an implantable loop recorder has a role in patients with syncope and conduction disturbances, negative tilt testing, and unexplained seizures, and may be superior to conventional testing with tilt and electrophysiologic studies. (J Cardiovasc Electrophysiol, Vol. 14, pp. S70-S73, September 2003, Suppl.)