Long-Term Drug Treatment of Obesity in a Private Practice Setting

ATKINSON, RICHARD L, ROY C BLANK, DONALD SCHUMACHER, NIKHIL V DHURANDHAR, DOUGLAS L RITCH. Long-term drug treatment of obesity in a private practice setting. This study evaluated the long-term efficacy and safety of the combination of phentermine and fenfluramine for the treatment of obesity in a private practice setting. A total of 1388 consecutive, qualified patients presenting to a private general internal medicine practice in Charlotte, NC, were enrolled with eligibility criteria including: age 18 years to 60 years, 20% over “desirable” bodyweight or body mass index <27, no serious medical or psychiatric disease, and no contraindications to drug therapy. Patients were instructed in diet, exercise, and behavior modification techniques and received phentermine (15 mg/day to 30 mg/day) and fenfluramine (20 mg/day to 60 mg/day) continuously for over 3 years. Average duration of treatment was 15. 9 months, and average weight loss at the last visit was 11. 6 kg, or 11. 7% of initial bodyweight. For patients completing 1 year of drug treatment, mean weight loss was 16. 5 kg, or 16% of initial weight. Weight loss persisted for 2 years, but partial regain was seen at 3 years. The dropout rates were 18% at 6 months, 39% at 1 year, 68% at 2 years, and 78% at 3 years. At 1 year, blood pressure of hypertensive patients fell from 151/95 mm Hg to 127/78 mm Hg, and serum cholesterol and triglycerides of hyperlipidemic patients fell by 0. 750 mmol/L (29 mg/dL) and 0. 937 mmol/L (83 mg/dL), respectively. Adverse events were modest. We conclude that, in a private practice setting, long-term treatment of obesity with the combination of phentermine, fenfluramine, and a weight maintenance program is generally safe and effective. More research is needed to determine efficacy and safety for longer than 3 years.     

Physiologic regulation of mixtalol in rape senescence and its yield effects

Physiologic and yield effects of mixtalol at various concentrations sprayed on rape at the anthesis stage were examined. Foliar sprays of 4 and 2 ppm mixtalol significantly increased the chlorophyll content of rape leaves and pods, reduced the accumulation of malondialdehyde and ethylene production, and delayed the degradation of superoxide dismutase and catalase activities of the rape plant. Mixtalol also increased root oxidizability. Meanwhile, the number of branches and pods per plant was increased, and a 10.7% and 8.2% increase of seed yield over the controls was observed with treatments of 4 and 2 ppm mixtalol, respectively. No significant effects from mixtalol were observed on the maturation of plants or on the seed oil content or the erucic acid and glucosinolate content. Total rape oil production increased with 4 and 2 ppm mixtalol significantly by 12.4% and 10.5%, respectively, over the controls.Abbreviations MTL mixtalol - MDA malondialdehyde - TBA thiobarbituric acid - SOD Superoxide dismutase - CAT catalase - TTC tetrazolium     

Interactions in cytochrome oxidase: Functions and structure

Mitochondrial cytochromec oxidase is an exceedingly complex multistructural and multifunctional membranous enzyme. In this review, we will provide an overview of the many interactions of cytochrome oxidase, stressing developments not covered by the excellent monograph of Wikström, Krab, and Saraste (1981), and continuing into early 1983. First we describe its functions (both in the nominal sense, as a transporter of electrons between cytochromec and oxygen, and in its role in energy transduction). Then we describe its structure, emphasizing the protein (its structure as a whole, the number and stoichiometry of its subunits, their biosynthetic origin, and their interactions with each other, with other components of the enzyme complex, and with the membrane as a whole). Finally, we present a model in which the protein conformation serves as the focus for the dynamic interaction of its two major functions.Abbreviations DCCD N,N-dicyclohexylcarbodiimide - E _m midpoint potential - EPR electron paramagnetic resonance - F₁ soluble portion of the ATP synthetase complex - NMR nuclear magnetic resonance - PAGE polyacrylamide gel electrophoresis - SDS sodium dodecyl sulfate - SUPAGE SDS-urea-PAGE     

Effects of prostaglandin E2, 16,16-dimethyl prostaglandin E2 and a prostaglandin endoperoxide analogue (U-46619) on gastric secretory volume, [H] and mucus synthesis and secretion in the rat

The effects of orally administered prostaglandin E₂, 16,16-dimethyl prostaglandin E₂ and U-46619, an analogue of the prostaglandin endoperoxide PGH₂, on gastric secretory volume, acid and mucus were studied in the rat. All of the compounds significantly increased the volume of gastric secretion, mucus secretion, measured as N-acetylneuraminic acid and mucus synthesis measured as the incorporation of [³H]-glucosamine into mucosal glycoprotein; however, only PGE₂ and 16,16-dimethyl PGE₂ inhibited acid secretion. U-46619, 1.5 mg/kg provided significant protection against ethanol-induced gastric ulcers, an effect that has been previously shown for the other two compounds. These studies provide additional evidence that prostaglandin induced mucosal protection may by related to an effect on mucus and on stimulation of nonparietal cell gastric secretion. Further study of these parameters may be important in the development of antiulcer drugs for long term clinical use.     

The role of arachidonic acid in vasogenic brain edema

Arachidonic acid is released rapidly from cellular membrane phospholipids after pathological insults associated with the delayed development of brain edema. Intracerebral injection of arachidonic acid caused significant increases in brain water and sodium content with decreases in potassium content and Na+,K+-ATPase activity. The 125I-labeled bovine serum albumin spaces in brain (a measure of blood-brain barrier permeability) rose threefold 24 h after arachidonic acid injection. There was gross and microscopic evidence of edema. Saturated fatty acids and monounsaturated fatty acids were not effective. These data indicate that the endothelial cells of the blood-brain barrier are target sites for the action of arachidonic acid. It is hypothesized that the increased permeability of endothelial cells to macromolecules and water results from alterations of membrane phospholipids and increased vesicular transport, changes that are responsible for the delayed development of vasogenic edema.     

Expression and function of I region determinants on immunocompetent cells. I. Selective expression of I-C region determinants on immune cells.

We have examined the cytotoxic activity of anti-Iak serum and complement on various immune functions of BALB/c (H-2d) cells. Since the cytotoxic action of this antiserum on H-2d cells defines specificity Ia.7, an I-C region product, we have looked at the selective expression of this antigen. We have mainly used the in vitro anti-Lac2 response to study the cells involved in the induction and regulation of antibody. The data presented here show that Ia.7 is present on both IgM and IgG precursor B cells and in lesser amounts on plaque-forming cells. The antiserum also recognizes with less efficiency a product on specific T suppressor cells, which is possibly coded for by the adjacent I-J subregion. Both fluorescence and functional tests indicate the absence of Ia.7 on macrophages. It is also lacking on T helper cells. When we tested the antiserum on the in vitro cytotoxic responses to alloantigens, we found that neither T effector cells nor their precursors were affected.     

Inhibition of nucleotidyl transferase enzymes by metal ions in combination with 5-amino-1-formylisoquinoline thiosemicarbazone.

Inhibition of urchin polymerases by the metal ions Fe⁺² and Cu⁺² is modulated by exogenous ligands and the resultant inhibition is further a function of the polymerase class. The DNA polymerase β is singularly resistant to Fe⁺² and Cu⁺² metal ions alone and in combination with the title ligand. DNA polymerase α and the RNA polymerases II and III show varying degrees of sensitivity to the title inhibitor.