We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.

OBJECTIVE -To characterize potential differences in glycemic control, plasma lipid level, and weight in a cohort of patients previously treated with troglitazone (TROG) who were switched to either pioglitazone or rosiglitazone. RESEARCH DESIGN AND METHODS-After a 2-week washout from TROG, 186 patients were randomly assigned to receive either pioglitazone (PIO) or rosiglitazone (ROSI). Weight, HbA 1c , and fasting lipid profile were documented before discontinuing TROG and at 4 months after starting either pioglitazone or rosiglitazone. Secondarily, the effect of concurrent medications on study outcomes was assessed.RESULTS -A total of 127 patients completed follow-up: 67 individuals in the PIO group (32 women, 35 men) and 60 individuals in the ROSI group (33 women, 27 men). There were no significant differences in gender mix, age, weight, fasting lipid profile, or HbA 1c between the ROSI and PIO groups. After 4 months of randomized treatment, no change in HbA 1c from baseline between or within groups was noted. Both groups experienced an equal and significant increase in weight from baseline of ϳ2.0 kg. Thiazolidinedione and HMG-CoA reductase inhibitor therapy had significant and independent effects on lipid profile (P Ͻ 0.005). Significant improvements in lipid profile were noted in the PIO group (P Ͻ 0.01), whereas none were detected with conversion to ROSI. Specifically, the PIO group experienced an average decrease in total cholesterol of ϳ20 mg/dl. CONCLUSIONS -Differing effects on lipid profile were apparent after random conversion from TROG to either PIO or ROSI, despite similar weight increase and glycemic control. The clinical significance of these differences remains to be determined, and further comparative research is warranted. Diabetes Care 25:708 -711, 2002R osiglitazone (ROSI), pioglitazone (PIO), and troglitazone (TROG) are all thiazolidinediones used in the management of diabetes. TROG has been withdrawn from the market because of concerns over hepatotoxicity, which is presumed to be idiosyncratic. These drugs all have effects on glucose and lipid metabolism as well as body weight (1-4). There are demonstrated differences in pharmacological effects of these drugs in vitro (5-7). However, there is little comparative data available on their relative clinical effects (8 -11). The removal of troglitazone from the market provided a unique opportunity to assess possible differences in clinical response with conversion to either PIO or ROSI. Therefore, we designed and implemented a protocol to assess several routine clinical end points in our TROG-treated patients after random assignment to PIO or ROSI. RESEARCH DESIGN AND METHODS Study designThis was an open-label, randomized comparison of PIO and ROSI in patients prev i o u s l y s t a b i l i z e d o n T R O G i n combination with various other glucoselowering medications. All patients were derived from a single diabetes center associated with a major teaching hospital serving a large metropolitan, Midwestern city. As outlined by the Declaration of...

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ABSTRACT:Vaccination against nicotine is being studied as a potential treatment for nicotine dependence. Some of the limitations of vaccination, such as variability in antibody titer and affinity, might be overcome by instead using passive immunization with nicotinespecific monoclonal antibodies. The effects of antibodies on nicotine distribution to brain were studied using nicotine-specific monoclonal antibodies (NICmAbs) with K d values ranging from 60 to 250 nM and a high-affinity polyclonal rabbit antiserum (K d ‫؍‬ 1.6 nM). Pretreatment with NICmAbs substantially increased the binding of nicotine in serum after a single nicotine dose, reduced the unbound nicotine concentration in serum, and reduced the distribution of nicotine to brain. Efficacy was directly related to antibody affinity for nicotine. Efficacy of the highest affinity NICmAb, NICmAb311, was dose-related, with the highest dose reducing nicotine distribution to brain by 78%. NICmAb311 decreased nicotine clearance by 90% and prolonged the terminal half-life of nicotine by 120%. At equivalent doses, NICmAb311 was less effective than the higher affinity rabbit antiserum but comparable efficacy could be achieved by increasing the NICmAb311 dose. These data suggest that passive immunization with nicotinespecific monoclonal antibodies substantially alters nicotine pharmacokinetics in a manner similar to that previously reported for vaccination against nicotine. Antibody efficacy is a function of both dose and affinity for nicotine.

The concentrations in cord blood of total immunoglobulin G (IgG) and the four subclasses of IgG were measured in 34 fetuses at a mean gestational age of 25 weeks (range, 18 to 35 weeks). The blood samples were obtained by percutaneous umbilical blood sampling, and results were compared with the respective IgG subclass concentrations of the mothers. The efficiency of transplacental transfer of the different IgG subclasses was determined. Transfer of IgG1 and IgG4 was found to be significantly more efficient than that of IgG3 and IgG2. IgG2 was the subclass least efficiently transferred from mother to fetus. These differences may partly explain the susceptibility of newborns to various pathogens, such as streptococcus group B.

Obese patients who took fenfluramine and phentermine, dexfenfluramine alone, or dexfenfluramine and phentermine had a significantly higher prevalence of cardiac valvular insufficiency than a matched group of control subjects.

Anticoagulation was more predictable with argatroban than with heparin as measured by ACT and aPTT, with comparable safety profiles.

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