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Characterization of cutaneous primary afferent fibers excited by acetic acid in a model of nociception in frogs.

Acetic acid applied to the hind limb of a frog evokes nocifensive behaviors, including a vigorous wiping of the exposed skin, referred to as the wiping response. The aim of this study was to examine the responses of cutaneous primary afferent fibers in frogs to acetic acid (pH 2.84-1.42) applied topically to the skin. Conventional electrophysiological methods were used to record neuronal activity from single identified primary afferent fibers with cutaneous receptive fields on the hind limb. Fibers were classified according to their conduction velocities and responses evoked by mechanical and thermal (heat and cold) stimuli. One hundred and twenty-two mechanosensitive afferent fibers were studied (44 Abeta, 60 Adelta, and 18 C fibers). Thirty-nine percent of all fibers were excited by acetic acid, but a greater percentage of Adelta (52%) and C fibers (44%) were excited than Abeta fibers (20%). Evoked responses of fibers increased with increasingly more acidic pH until the greatest responses were evoked by acetic acid at pH 2.59-2.41. Application of acetic acid at pHs <2.41 evoked less excitation, suggesting that fibers became desensitized. Similar percentages of nociceptors and low-threshold mechanoreceptors were excited by acetic acid. Thus primary afferent fibers were excited by acetic acid at pHs that have been shown to evoke the wiping response in our previous study. The results of the present study suggest that the model of acetic acid-induced nociception in frogs may be useful for studying the mechanisms by which tissue acidosis produces pain.

Acetic Acid↗

Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study.

PURPOSE: To determine whether dronabinol administered alone or with megestrol acetate was more, less, or equal in efficacy to single-agent megestrol acetate for palliating cancer-associated anorexia. PATIENTS AND METHODS: Four hundred sixty-nine assessable advanced cancer patients were randomized to (1) oral megestrol acetate 800 mg/d liquid suspension plus placebo, (2) oral dronabinol 2.5 mg twice a day plus placebo, or (3) both agents. Eligible patients acknowledged that loss of appetite or weight was a problem and reported the loss of 5 pounds or more during 2 months and/or a daily intake of less than 20 calories/kg of body weight. RESULTS: Groups were comparable at baseline in age, sex, tumor type, weight loss, and performance status. A greater percentage of megestrol acetate-treated patients reported appetite improvement and weight gain compared with dronabinol-treated patients: 75% versus 49% (P =.0001) for appetite and 11% versus 3% (P =.02) for > or = 10% baseline weight gain. Combination treatment resulted in no significant differences in appetite or weight compared with megestrol acetate alone. The Functional Assessment of Anorexia/Cachexia Therapy questionnaire, which emphasizes anorexia-related questions, demonstrated an improvement in quality of life (QOL) among megestrol acetate-treated and combination-treated patients. The single-item Uniscale, a global QOL instrument, found comparable scores. Toxicity was also comparable, with the exception of an increased incidence of impotence among men who received megestrol acetate. CONCLUSION: In the doses and schedules we studied, megestrol acetate provided superior anorexia palliation among advanced cancer patients compared with dronabinol alone. Combination therapy did not appear to confer additional benefit.

Administration, Oral↗

An overview of acetic acid ulcer models--the history and state of the art of peptic ulcer research.

Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers >100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.

Acetic Acid↗

[An overview of acetic acid ulcer models and their utility for drug screening].

Since Takagi et al. reported an experimental chronic gastric ulcer model [acetic acid ulcers induced by submucosal injection of acetic acid (Type 1)], we further modified the methodology and subsequently devised three more models. The second model involves inducing ulcers by serosal application of an acetic acid solution (Type 2) and the third model achieves ulcer induction by intragastric application of an acetic acid solution (Type 3). The forth model was modification of the third model by giving the acetic acid solution and the same volume of air to make one ulcer in the stomach (Type 4). In general, animals accepted the procedures without problems and no undesirable effects were noticed. More importantly, this experimental animal model allows production of ulcers that highly resemble human ulcers in terms of both pathology and healing. Indeed, relapse is even endoscopically observed for 360 days after ulceration. The ulcers produced not only respond well to various anti-ulcer medications, such as antisecretory and mucosal protective drugs and growth factors, but also demonstrate appropriate responses to ulcerogenic agents such as NSAIDs. In addition, we have recently demonstrated that H. pylori infection resulted in delayed ulcer healing and recurrence of healed acetic acid ulcers induced in Mongolian gerbils. The present article gives a brief summary of the ulcer history before establishment of acetic acid ulcers and characteristic features of acetic acid ulcer, including both their merits and shortcomings.

Acetates↗

Effects of short- or long-term infusions of acetate or propionate on luteinizing hormone, insulin, and metabolite concentrations in beef heifers.

Two trials were conducted to evaluate the effects of short- (Trial 1) or long-term (Trial 2) intraruminal isocaloric infusions of acetate or propionate on secretion of LH, insulin, and selected metabolites in short- or long-term energy-restricted beef heifers. In Trial 1, 16 Angus heifers were assigned on d 6 to 12 of a synchronized estrous cycle (estrus = d 0) to a body weight-maintenance (BWM; n = 4) or an energy-restricted, body weight-loss (BWL; n = 12) treatment. On d 12 of a synchronized estrous cycle, heifers received PGF2alpha to synchronize estrus, and 12 h later BWL heifers received intraruminal, isocaloric infusions of acetate, propionate, or vehicle for 6 h and BWM heifers received vehicle concurrently. Mean plasma LH and LH pulse frequencies and amplitudes were not affected by treatment (P > .05). In contrast, infusion of propionate increased plasma insulin (P < .05) and reduced plasma concentration of NEFA (P < .05). In Trial 2, six ovariectomized Angus heifers were energy-restricted for 30 d. On d 14 and 26 of restriction, heifers began receiving intraruminal isocaloric infusions of acetate or propionate for 96 h in a switchback approach. Intraruminal infusions of vehicle for 6 h preceded infusions of acetate or propionate. Jugular blood was collected at 12-min intervals during infusions of vehicle and during the last 6 h of infusion of acetate or propionate. Mean concentration of LH and amplitude of pulses of LH were lower during acetate vs propionate or vehicle infusion (P < .05). Infusion of propionate increased insulin relative to acetate or vehicle infusion (P < .05). Plasma NEFA were reduced by infusion of propionate (P < .05) and increased by infusion of acetate (P < .05).

3-Hydroxybutyric Acid↗

Kinetics of infused acetate and effect on plasma pyruvate and lipid concentrations in uremic and non-uremic dogs.

During acetate infusion at a rate of 10 millimoles/kg/hr arterial blood acetate levels rose progressively to maximums of 7.9 +/- 1.7 mM in uremic dogs and 10.8 +/- 1.4 mM in non-uremic dogs. Following cessation of infusion, removal of acetate followed first order kinetics. Acute uremia had no significant effect on mean clearance rates of acetate (1.28 +/- 0.28 L/kg/hr uremics vs 0.92 +/- 0.22 in non-uremics) or upon blood half-life of acetate following infusion (9.7 min. vs 10.9 min.). Plasma pyruvate levels rose during infusion from 1.5 to 4.4 mg/dl in the uremic dogs and following infusion rose further to 6.5 mg/dl. In the non-uremic dogs pyruvate was not significantly elevated until 30 min. post-infusion. Plasma free fatty acids increased from 79 to 131 mumoles/dl during acetate infusion in the uremic dogs, but did not change significantly in the non-uremic group. Plasma cholesterol and triglycerides increased after induction of uremia, but showed no significant changes as a result of acetate infusion in either group. These results suggest that the electrolyte and lipid abnormalities that occur in hemodialyzed uremic patients may be related to the acetate load these patients receive during dialysis.

Acetates↗

Labeled acetate incorporation into lipids and lipid elimination after oral administration in rat liver and adipose tissue.

To investigate the incorporation of acetate into fatty acids and their turnover, the time courses for the incorporation of labeled acetate into lipids in the liver and epididymal adipose tissue (adipose tissue) after the oral administration to rats were examined for 10 d. The labeled acetate was abundantly incorporated into lipids, mainly into triacylglycerols (TAG) in the liver, reached a maximum at 2 h after the administration and then quickly decreased. In the adipose tissue, the incorporation of the acetate reached a maximum after 8 h and began to decrease slowly after 2 d. The acetate incorporation into the lipids was markedly lower in the liver, plasma and adipose tissue of rats fed the corn oil diet than in those fed the fat-free diet. However, the half-lives of esterified fatty acids were similar in both dietary groups. The half-lives of esterified C16:0 and C18:1 in the decreasing phase were 5.4 and 8.9 h, respectively, in the liver, and 4.3 and 5.6 d, in the adipose tissue. The time courses for incorporation into plasma lipids were parallel to those in the liver. Thus the fatty acids synthesized in the liver appeared to be transported to adipose tissues and to stay there longer. Moreover, it is remarkable that 30% of the acetate radioactivities administered were found after 2 h in the whole liver: 75% of the products from the acetate at the maximum were lipids and 61%, of the lipids, TAG. The major products from acetate in the liver were lipids.

Acetates↗

Combination spray washes of saponin with water or acetic acid to reduce aerobic and pathogenic bacteria on lean beef surfaces.

Saponins are naturally occurring compounds known as triterpenoid glycosides found in a variety of plant species. Saponins are approved for use in the food industry as foaming agents. When combined with water or organic acid in spray treatments, saponins' foaming property may improve carcass decontamination. In the first experiment of this study, lean beef carcass surfaces were experimentally inoculated with a fecal slurry containing antibiotic-resistant Escherichia coli O157:H7 and Salmonella Typhimurium. Spray-washing treatments with 1% saponin followed by a water wash, or 1% saponin followed by 2% acetic acid, were more effective for reducing aerobic bacteria than saponin, water, or 2% acetic acid washes alone. However, 1% saponin followed by a either a water or 2% acetic acid wash was no more effective than a 2% acetic acid wash for reducing populations of E. coli O157:H7 or Salmonella Typhimurium. In the second experiment, experimentally inoculated beef surfaces were subjected to spray treatments with water followed by another water wash, water followed by a 2% acetic acid wash, 1% saponin followed by a water wash, or 1% saponin followed by a 2% acetic acid wash. When examined for effectiveness against all bacterial populations, 1% saponin followed by a water wash and 1% saponin followed by a 2% acetic acid wash were as effective as two water washes or a water wash followed by 2% acetic acid for reducing aerobic bacteria, E. coli O157:H7, and Salmonella Typhimurium from beef surfaces. Under the conditions described, reductions associated with combination spray washes may be attributed to the physical removal of bacteria during the spraying process, not to any specific action of saponin.

Acetates↗

Megestrol acetate in patients with AIDS and cachexia.

OBJECTIVE: To study the effects of a megestrol acetate liquid formulation (800 mg/d) on body weight, body composition, caloric intake, and mental outlook in patients with the acquired immunodeficiency syndrome (AIDS) who had cachexia. DESIGN: Twelve-week, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Multiple clinical centers. PATIENTS: 100 patients with AIDS who had weight loss of 10% or more of ideal body weight were randomly assigned to placebo (n = 48) or megestrol acetate (n = 52). MEASUREMENTS: Caloric intake, body weight, body composition, and sense of well-being. RESULTS: Most patients receiving megestrol acetate had increased caloric intake resulting in body weight gain (mainly fat mass). From baseline to week 8, the megestrol acetate group increased their daily caloric intake by 608 calories, whereas the placebo group increased intake by 134 calories (difference, 474 calories; 95% CI, -68 to 880 calories). Body weight in the megestrol acetate group increased by 3.86 kg from baseline to week 8, although it decreased by 0.46 kg in the placebo group (difference, 4.32 kg; CI, 2.42 to 6.22 kg). At week 8 in the megestrol acetate group, patients gained 3.68 kg in fat mass and those in the placebo group lost 0.28 kg (difference, 3.96 kg; CI, 2.49 to 5.43 kg). Body water, lean mass, and patient survival were not statistically different between treatment groups. Patients treated with megestrol acetate had an increased sense of well-being when compared with patients who received placebo. CONCLUSIONS: This megestrol acetate liquid formulation is well tolerated, increases food intake, results in body weight gain, and improves the sense of well-being in cachectic patients with AIDS.

Acquired Immunodeficiency Syndrome↗

Physical properties of acetic acid vital in evaluating the cervix for neoplastic changes.

INTRODUCTION: In a "developing country" the need exists for an inexpensive, simplistic yet sensitive screening procedure which furthermore, allows for the immediate referral of patients. Research has indicated that the acetic acid test is a most viable option. Screening, however, often occurs in less than ideal conditions thus implying the exposure of the acetic acid to various fluctuating elements. OBJECTIVE: Determining the influence of temperature, time and humidity on the pH of a 5% acetic acid solution. METHOD: The effect of temperature, time and humidity on the pH of a 5% acetic acid solution was determined under controlled laboratory conditions utilizing the calculated molar conductance and dissociation constant. RESULTS: The pH of the 5% acetic acid solution remained a constant throughout exposure to the various elements. DISCUSSION: The results imply that the quality of acetic acid, on which many alternative screening methods and colposcopy are based, remains stable under varying conditions. This is important when screening is implemented in less than ideal conditions utilizing cervicography or the acetic acid test which are primarily dependent on acetic acid.

Acetic Acid↗

[1-(11)C]Acetate as a quantitative perfusion tracer in myocardial PET.

UNLABELLED: Our objective was to investigate the properties of [1-(11)C]acetate as a quantitative perfusion tracer for myocardial PET studies. METHODS: We determined the flow dependence of the effective acetate extraction by a comparison with [(13)N]ammonia in 24 patients at rest (n = 8) and under pharmacologic vasodilation (n = 16). Furthermore, we compared the statistical quality of the perfusion values derived with both tracers. Quantification was based on an irreversible 2-compartment model for [(13)N]ammonia and a reversible 1-compartment model for [1-(11)C]acetate. Area-conserving polar maps were used to determine the correlation between the unidirectional uptake parameters of both tracers on a pixel-by-pixel basis for the whole left ventricular myocardium. RESULTS: A fit of a generalized Renkin-Crone formula to the data yielded the unidirectional acetate extraction fraction E(f) = 1 - 0.64e(-1.20/f). An extraction correction based on this formula led to good quantitative agreement of perfusion values derived with [(13)N]ammonia and [1-(11)C]acetate over the whole observed flow range (average difference of flow values, 3%; correlation coefficient, 0.96). This agreement proved the applicability of acetate as a quantitative perfusion tracer even under stress conditions. An analysis of the statistical properties of the parameter estimates showed, moreover, that statistical errors were reduced by a factor of nearly 2 in comparison with ammonia. CONCLUSION: [1-(11)C]acetate allows accurate quantification of myocardial perfusion with PET at rest as well as under stress conditions. The use of acetate leads to distinctly improved statistical accuracy for the perfusion estimates in comparison with ammonia. This accuracy facilitates the generation of reliable parametric polar maps, which are especially useful for clinical application of myocardial perfusion quantification.

Acetic Acid↗

Biphasic urethral sphincter responses to acetic acid infusion into the lower urinary tract in anesthetized cats.

PURPOSE: Varying the concentration of infused acetic acid produced bladder irritation and dose dependent increases in external urethral sphincter electromyography activity in cats. We further characterized acetic acid induced external urethral sphincter electromyography activity in intact and acute spinal cord injured animals. MATERIALS AND METHODS: Bladder cystometrography and external urethral sphincter electromyography were continuously recorded in chloralose anesthetized cats. Dilute 0.05% to 0.8% acetic acid was infused into the lower urinary tract through the bladder dome. Intravesical or intraurethral infusion was performed separately in bladder neck ligated preparations. In some animals the spinal cord was transected at L1 to L2 2 to 8 hours before the study. RESULTS: Acetic acid infusion into the lower urinary tract elicited dose dependent increases in tonic external urethral sphincter activity. However, a prolonged infusion of 0.7% to 0.8% acetic acid usually inhibited external urethral sphincter activity. The excitatory external urethral sphincter response was elicited by intraurethral but not by intravesical infusion. This response remained in acute spinal cord injured animals. The inhibition of tonic external urethral sphincter activity during 0.7% to 0.8% acetic acid infusion was observed when there was extreme bladder irritation characterized by continual contractions. Induced tonic external urethral sphincter activity was attenuated by intrathecal administration of prazosin or scopolamine and abolished by hexamethonium. CONCLUSIONS: Acetic acid infusion into the lower urinary tract elicits biphasic external urethral sphincter responses. The early excitatory response is a spinal urethrourethral reflex and the late inhibitory phase results from negative vesicourethral feedback control. Spinal muscarinic cholinergic and alpha-adrenergic receptors are involved in acetic acid induced excitatory external urethral sphincter responses.

Acetic Acid↗

Conversion of fatty aldehyde dimethyl acetals to the corresponding alk-1-enyl methyl ethers (substituted vinyl ethers) during gas-liquid chromatography.

The behavior of palmitaldehyde and linolealdehyde and of their dimethyl acetals during gas-liquid chromatography on beta-cyclodextrin acetate (beta-CDX acetate) and ethylene glycol succinate polyester-phosphoric acid (EGSP) columns was studied. The aldehydes were well separated from their dimethyl acetals on the beta-CDX acetate column. However, on the EGSP column the retention times of palmitaldehyde and its dimethyl acetal were identical; a mixture of linolealdehyde and its dimethyl acetal gave a split peak. The aldehydes were recovered unchanged in 80-85% yield by preparative GLC from both columns, but the dimethyl acetals were quantitatively converted to the corresponding alk-1-enyl methyl ethers. The structure of these compounds was elucidated by infrared spectroscopy, mass spectrometry, and chemical means. Upon hydrolysis at low temperatures with 100% H(2)SO(4) they yielded the corresponding aldehydes, which were identified as 2,4-dinitrophenylhydrazones.

Acetals↗

[Formation of an acetic-acid type microbial metabolism pathway and its stability during the course of sulfate-reduction].

Continuous-flow experiment was conducted in an acidogenic sulfate-reducing reactor supplied with molasses as sole carbon resource and sulfate sodium as electron acceptor. The composition of Volatile fat acid(VFA) in terminal liquid products, the distribution of acetic acid, the existence of microbial populations and the interspecific relationship between sulfate-reducing bacteria (SRB) and acidogenic bacteria (AB) were investigated in different experimental stages when sulfate removal rate and gas production maintained at a relatively stable status. The experimental results showed that an acetic-acid type microbial metabolism pathway was formed based on the fact that the proportion of acetic acid in terminal liquid products was as high as 50% to 82%. It was also explained the formation of acetic-acid type microbial metabolism pathway was resulted from acetic acid accumulation in the terminal liquid products, which was subjected to the bio-chain cooperation relationship between populations of SRB and AB, and the incomplete-oxidation of organic substance in acidogenic-phase reactor of two-phase anaerobic treatment process. It was also presented that the formation of acetic-acid type microbial metabolism pathway depended on the capability of acetic-acid utilized-SRB (ASRB) population competing against other populations and its ability of acetic acid consumption. Furthermore, this kind of metabolism pathway could offer suitable carbon resource for methane producing reactor in the two-phase anaerobic treatment process, and has significant effect on the sulfate removal rate of the whole treatment system and its running stability.

Acetic Acid↗

[Selection of acetate-tolerant mutants from Escherichia coli DH5alpha and the metabolic properties of mutant DA19].

Esherichia coli DH5alpha is one of the widely used host strains in genetic engineering. However, foreign gene expression level in this strain is seriously inhibited due to its great sensitivity to the accumulated metabolite, acetate. This study aimed at improving the tolerance of this strain against acetate. Cells of E. coli DH5alpha were irradiated with 60Co, and subsequently continuous culture of the irradiated cells was conducted with gradual increase in the dilution rate and the selective pressure, acetate concentration in the medium. The mutants were picked up on MA plates which contained 5g/L sodium acetate. 5 strains with great improvement in acetate tolerance were obtained, among which DA19 was the best. In cultivation of DA19 in complex media YPS and YPS2G, the cell density, maximum specific growth rate and acetate produced were respectively 1.17 and 1.05, 1.08 and 1.27, and 0.06 and 0.59 times of those of DH5alpha. In a chemically defined medium, the cell density of DA19 was 3.4-fold of that of DH5alpha. The cell density of DA19 in a medium containing 10g/L sodium acetate was comparable to that of DH5alpha in the same medium without the addition of acetate.

Acetates↗

Escherichia coli acetate kinase mechanism studied by net initial rate, equilibrium, and independent isotopic exchange kinetics.

The equilibrium constant of the reaction catalyzed by acetate kinase (E.C. 2.7.2.1.) was determined: K = (MgADP) (acetylphosphate)/(MgATP)(acetate) = 6.7 +/- 1.3 X 10 (-4) (pH 7.4, 25 degrees). The respective free nucleotides uncomplexed to magnesium inhibit the net reaction in both directions: competitively with the respective magnesium nucleotide (MgATP or MgADP) and noncompetitively with the co-substrate (acetate or acetylphosphate). Excess free magnesium also inhibits the net reaction in both directions. The inhibition is not competitive with the phosphoryl donor (MgATP or acetylphosphate) but is competitive with respect to the phosphoryl acceptor (acetate or MgADP). A 50-fold increase in concentration of reactants at equilibrium in 0.1 M Tris/HCl, pH 7.4, at 25 degrees resulted in a rise to plateau levels of the acetate equilibrium acetylphosphate exchange rate (measured with [U-14C]acetate) and of the ATP equilibrium ADP exchange rate (measured with [U-14C]ADP and 10-fold higher than acetate equilibrium acetylphosphate), suggesting that there is no compulsory order of binding of magnesium nucleotide and co-substrate and that all chemical transformation steps cannot be much slower than the dissociation steps. The ATP equilibrium ADP exchange rate was independent of the presence or concentration of co-substrate, whereas the acetate equilibrium acetylphosphate exchange reaction occurred only in the presence of magnesium nucleotide, and the rate was directly related to the degree of saturation of enzyme with magnesium nucleotide. The independent ATP equilibrium ADP exchange, which presumably involves a phosphoenzyme intermediate, was progressively inhibited by increasingly elevated MgADP concentrations (when MgADP/MgATP greater than or equal 5), but increasing MgATP/MgADP was not inhibitory, suggesting that MgADP may bind to nonphosphorylated as well as phosphorylated enzyme, but that MgATP cannot bind to phosphorylated enzyme. While direct transfer of the phosphoryl group between nucleotide and co-substrate in a concerted mechanism has not been ruled out, an "activated ping pong" mechanism can also be proposed which is compatible with the isotopic exchange and initial net rate kinetic results. This mechanism includes a phosphoenzyme intermediate and requires enzyme-bount MgADP for phosphorylation of the enzyme by acetylphosphate.

Acetates↗

[The effect of acetate and bicarbonate on the tolerance for hemodialysis therapy in chronic kidney failure].

Effects of acetate and bicarbonate dialysates on tolerance to dialysis have been examined in 30 patients with chronic renal failure (CRF). Symptomatic homeostatic impairment (nausea, vomiting, headache) and cardiovascular instability (tachycardia, arrhythmia, dyspnea) were less common (p less than 0.05) in bicarbonate dialysis. The cardiovascular symptoms correlated with antihypertensive effects of acetate (p = +0.48). Tolerance to ultrafiltration was better with bicarbonate dialysis. Gas chromatographic measurement of blood acetate concentrations in 7 patients on bicarbonate dialysis showed them to be 1.4 +/- 0.31 mmol/l at the beginning of dialysis treatment and 1.7 +/- 0.24 mmol/l at its end (normal, 1.7 +/- 0.14 mmol/l). Of 26 patients on acetate dialysis, 9 patients showed initial and late acetate concentrations of 1.7 +/- 0.26 and 2.5 +/- 0.23 mmol/l, respectively, while in 17 patients an initial concentration of 4.8 +/- 0.32 mmol/l rose to 9.0 +/- 1.1 mmol/l at the end of the treatment (p less than less than 0.01). Dialysis-induced complications had a higher incidence in the latter group (p less than 0.02). Acetate dialysis was poorly tolerated by 65% of the patients. The intolerance was aggravated by myocardial lesions and slow acetate turnover indicated by blood acetate concentrations above 7-8 mmol/l.

Acetates↗

Megestrol acetate for treatment of anorexia and cachexia associated with human immunodeficiency virus infection.

Cachexia is a common problem in persons infected with the human immunodeficiency virus (HIV). Megestrol acetate, an agent used for the treatment of metastatic breast cancer, is associated with appetite stimulation and weight gain. To determine whether this drug might benefit HIV-positive patients, 22 such subjects (14 previously reported) were treated with oral megestrol acetate, beginning at a dose of 80 mg four times daily. All patients had lost at least 10% of their preillness weight prior to treatment; the median loss was 11.4 kg (range, 5.5 to 26.8). Preliminary data from patients observed during therapy from 2 to 72 weeks showed that 21 of the 22 patients gained weight; the average weight gain was 7.3 kg (range, -4.1 to 17.3). Three patients failed to gain weight on 320 mg per day of megestrol acetate; both appetite stimulation and weight gain were achieved with 460 mg per day in one and 640 mg per day in another. One patient continued to lose weight despite 480 mg per day megestrol acetate. The median time to peak weight during megestrol acetate treatment was 14 weeks. Seven patients returned to within 1 kg of their normal body weight. In three of the 22 patients treated, megestrol acetate and zidovudine were started simultaneously. For these three patients, weight gain was potentially due to the recognized weight gain associated with the initiation of zidovudine. For the remaining 18 patients, however, appetite stimulation and weight gain were a result of megestrol acetate. All patients tolerated the drug well. One patient developed a deep vein thrombosis. No patient developed peripheral edema or drug-related impotence. The appetite improvement and weight gain seen in this initial series are encouraging. The true effectiveness of megestrol acetate for HIV-related cachexia and the effects of treatment on quality of life are currently being assessed in a national prospective, randomized, double-blind, placebo-controlled trial.

Acquired Immunodeficiency Syndrome↗