Methods to Maximize Retention in Weight Loss Studies

GREENWAY, FRANK L., GEORGE A. BRAY, AND ROBERT L. MARLIN. Methods to maximize retention in weight loss studies. Obes Res. Objective: Dropouts from clinical trials decrease quality and increase costs. Free participation, paid participation, and contingency contracting are three study retention methods. Contingency contracting, or depositing a fee to be refunded contingent upon attendance in a clinical trial, has been reported to decrease dropouts without affecting weight loss. These three methods of retention were compared with a commercial weight loss clinic's practice of charging non-refundable fees. Methods and Procedures: Dropouts were compared in two studies testing mazindol, with one study using free care and the other using contingency contracting; two studies testing phenylpropanolamine, one using free care and the other using contingency contracting; and in studies with phenylpropanolamine on file with Thompson Medical Company using free care, paid participation, and contingency contracting. Results: The dropout rate was 50% at 8 weeks in a trial of mazindol with free care vs. 7% for contingency contracting (p <0. 001). The two phenylpropanolamine studies gave the same weight losses, but the dropouts were 37% at 8 weeks for free care vs. 11 % for contingency contracting (p<0. 001). The studies of phenylpropanolamine on file at the Thompson Medical Company had 28% dropouts at 8 weeks using free care vs. 19% for paid participation (p<0. 001), and 11% for contingency contracting (p<0.005). Dropouts with contingency contracting (11%) were not different from the commercial weight loss program (13%). Discussion: Contingency contracting can decrease dropouts, improve quality, and decrease costs without affecting weight loss in clinical trials for obesity.     

The metabolism of cinnamic acid by healthy and phenylketonuric adults: a kinetic study

The enzyme phenylalanine ammonia lyase taken orally has been found to reduce the rise in blood phenylalanine that normally occurs following a protein meal. Therefore the enzyme has a potential use in the management of the genetic disease phenylketonuria. The enzyme mediates the conversion of phenylalanine to cinnamic acid and its possible clinical future has necessitated a more detailed study of the product of its reaction. Cinnamic acid is a compound of low toxicity which is converted in the mammalian body primarily to hippuric acid. We have examined the kinetics of this process in a healthy male and in two patients with untreated phenylketonuria. In addition we have attempted to clarify the inconsistencies in earlier published work about the status of other, minor metabolites. Following an oral load of sodium (2H6) cinnamate there is an increase in urinary hippuric acid largely due to the excretion of (2H5) hippuric acid. In the subjects studied there was no major difference in the rate of elimination although the amount of cinnamic acid converted was less in those with phenylketonuria. This may reflect reduced first-pass absorption by the liver in untreated phenylketonuria enabling increased uptake to occur in other parts of the body.     

Rapid measurement of blood ethanol concentrations using the alcohol oxidase membrane technique

The alcohol oxidase membrane technique is available for measurement of ethanol in commercial fluids. In this paper we examined its usefulness for cat and human blood in comparison with gas-liquid chromatography (GLC). The membrane method proved to be simple, reproducible, accurate, and inexpensive. Analysis took 1-2 min per sample and required only 25 microL of whole blood for measurement of concentrations between 0.05 and 1.0 mM (0.25-5 mg/dL) and 10 microL of whole blood for measurement of concentrations between 1.0 and 40 mM (5-190 mg/dL). Background concentrations were undetectable in cats after extraneous sources of alcohols were removed. The alcohol oxidase membrane technique is less specific than GLC, but it may be useful when ethanol is administered after background samples have shown an absence of other nonspecific reactants. Its high sensitivity is useful for kinetic studies where blood ethanol concentrations are below or close to those required for maximal hepatic ethanol metabolism.     

Chemistry of the secretion from the cornicles of various species of aphids

The cornicle secretions from 28 species of aphids were examined directly by mass spectrometry and, in selected cases, by chemical and chromatographic methods. The major components of the secretions are triglycerides, the acid moieties of which are hexanoic, hexadienoic (sorbic), tetradecanoic (myristic), and hexadecanoic (palmitic) acids, with smaller amounts of C₁₂ and C_18:1 acids. The mixtures from the different species fall into six groups which are readily distinguished by mass spectrometry. The composition was independent of the host plant or of the stage of development where these have been investigated. Biochemical classification is not consistent with morphological classification in the species examined.     

Serum levels of the low-affinity interleukin-2 receptor molecule (TAC) during IL-2 therapy reflect systemic lymphoid mass activation

Summary Expression of the low-affinity interleukin-2 (IL-2) receptor molecule (TAC) has been associated with lymphocyte activation, in vitro and in vivo [Greene WC (1987) Clin Res 35:439]. We have used an enzyme-linked immunosorbent assay (ELISA) to quantify the role of released and cell-bound IL-2 receptor following in vitro or in vivo activation of human lymphocytes with IL-2. In vitro experiments, culturing fresh peripheral blood lymphocytes in 30 U/ml IL-2 (corresponding to the steady-state IL-2 concentration achieved in patients receiving IL-2 in our clinical trials), showed that the levels of IL-2 receptor released into the culture media exceeded the levels of cell-associated receptor, with both rising in parallel to the cytotoxic activity of the peripheral blood lymphocytes (PBL) against cultured tumor cells. In 12 patients receiving high-dose IL-2 for the treatment of various malignant neoplasms, the levels of IL-2 receptor released into the serum rose dramatically during the IL-2 infusion, and then fell following cessation of the IL-2 infusion. This heightened release of IL-2 receptor into the serum occurred during the episodes of profound lymphopenia that developed within hours after patients began an IL-2 infusion. Following each 4-day infusion of IL-2, a rebound lymphocytosis was observed, as has been previously reported. Serum IL-2 receptor levels do not rebound in parallel; rather, they reach a plateau near the end of the 4-day infusion and then decrease upon cessation of IL-2. These changes in serum IL-2 receptor levels accompany changes in lytic activity of circulating PBL on Daudi target cells. These results suggest that lymphocyte populations exposed to IL-2 in vivo are activated to become cytotoxic, release TAC, and relocate in non-peripheral blood compartments. Following cessation of the IL-2 infusion these activated lymphocytes return to the peripheral circulation and do not secrete TAC as vigorously as while influenced directly by the IL-2 infusion.This research was supported by NIH contract CM-47669, NIH grants CA-32685, and RR-03186, American Cancer Society CH-237B, and a research fellowship of the Leukemia Society of America (P. Fisch), a Ewing Foundation Fellowship (S. Voss) and Lutheran Brotherhood/Life and Health Insurance Medical Research Fund M. D./Ph. D. Training Fellowship (S. Voss)     

Effects of water stress on phosphorus transport to the xylem

Summary Tomato plants were treated for one hour in nutrient solutions at-10.4 atm. Roots were excised, transferred to solutions at-0.4 atm and put into a pressure chamber to induce rates of water flow similar to those in transpiring plants.For roots continuously at-0.4 atm, the xylem sap had much higher phosphorus concentrations than the external solution, which contained 6 p.p.m. phosphorus.Roots previously treated at-10.4 atm had much lower concentrations in the sylem sap than in the external solution and the amount of phosphorus transported and the water flow were linearly related. This phosphorus transport was due to passive movement as shown by measuring transport of both ³²P and ¹⁴C mannitol. Thus transport to the xylem mediated by active processes was abolished even though uptake by the roots remained substantial. These results obtained after plasmolysis support the view that radial transport to the xylem includes uptake into and movement through the symplast.