Step-down therapy for hypertension. Results in a community-based program

The study reported here involved a systematic attempt to withdraw medication from participants in a community-based hypertension treatment program. Sixty-six of 88 patients with well-controlled mild or moderate disease had medication withdrawn after at least six months of treatment; nonpharmacologic intervention was not employed. After one year, 44 (66.6%) remained normotensive and drug free; after two years, 33 (50.0%). Of the 29 patients still available for three-year follow-up, 15 (51.7%) were still normotensive and drug free. Withdrawal of medication was associated with correction of hypokalemia and reversal of impaired glucose tolerance. Thus, nearly one fourth of these patients, who were believed to be reasonably representative of those with mild or moderate hypertension, could discontinue drug therapy and remain normotensive for at least one year. Substantial medical and economic benefits are to be realized from wide replication of this experience.     

Hydrogen peroxide-mediated corneal endothelial damage. Induction by oxygen free radical

Polymorphonuclear leukocytes and other inflammatory cells release superoxide anion and additional oxidant species following stimulation. Corneal endothelial cells were exposed to a flux of chemically generated superoxide anion (oxygen-free radical) produced by the combination of 1 mM hypoxanthine and 0.06 U/ml xanthine oxidase. Exposure of endothelial cells to the combination of hypoxanthine and xanthine oxidase resulted in anatomic disruption of the cells with interference in the function of endothelial water movement and resultant swelling of the corneal stroma. Catalase reduced the corneal swelling caused by exposure of endothelium to the oxygen-free radical generating system, whereas superoxide dismutase, ascorbic acid, D-mannitol, and ethanol did not prevent damage. The data suggest that hydrogen peroxide produced during the dismutation reaction of the superoxide anion is one of the toxic species, whereas the superoxide anion itself and the hydroxyl-free radical probably do not participate. The data suggest that corneal endothelial cells are susceptible to physiologic and anatomic damage induced by the products of reactive oxygen species, which, from previous studies, are known to be generated by inflammatory cells. The development of therapeutic modalities directed at the prevention of damage produced by hydrogen peroxide and other oxidant species may be of benefit in reducing corneal endothelial cell damage secondary to ocular inflammatory disease processes.     

Asynergy of right ventricular wall motion in man

Canine studies have shown a correlation between instantaneous segmental lengths in the right ventricular free wall and chamber volume, pressure, and stroke work. To determine whether such correlations exist in intact man, we studied the temporal relationships between chord dynamics in various regions of the right ventricle in 21 heart transplant recipients with apparently normal right ventricular function. Patients were examined by biplane radiography while performing various maneuvers (e.g., Valsalva maneuver). Computer-aided analysis of biplane radiograms of five surgically inserted radiopaque tantalum right ventricular myocardial markers was used to calculate interpoint chord lengths at 33 msec sampling intervals. Two patterns of right ventricular chord asynergy were defined: (1) An akinetic chord had an amplitude of less than 2.0 mm during the course of at least one beat; (2) an out-of-phase chord was more than a quarter period out of phase from the average curve (derived from all concurrently measured marker pairs during each maneuver) for at least one beat. Considering all chords (n = 978), 60 chords (6.1%) were akinetic and nine chords (0.9%) were out of phase. Excluding the outflow tract markers (n = 581), 33 chords (5.7%) were akinetic and five chords (0.9%) showed out-of-phase movement. During some maneuver, at least one akinetic chord occurred in 57% of patients and out-of-phase chords in 33% of patients. Most right ventricular regions were implicated in asynergic motion, including the right ventricular free wall, acute margin, and outflow tract. The frequency and distribution of asynergy in right ventricular chord dynamics observed in this study suggests that changes in a single right ventricular dimension may not accurately reflect global right ventricular events.     

Mechanism of platelet interference with measurement of lactate dehydrogenase activity in plasma

Platelets reportedly inhibit lactate dehydrogenase activity in plasma under reaction conditions of low osmolality. We describe observations inconsistent with these reports, and we attribute this "inhibition" to optical interference by platelets during the course of a reaction. We conclude that when platelet lysis is prevented and the optical interference of platelets corrected, platelet-rich plasma, platelet-poor plasma, and serum show essentially the same lactate dehydrogenase activity. Furthermore, platelet contamination can cause unexpected problems when lactate dehydrogenase is assayed with centrifugal analyzers. Results can be high or low, depending on the volume of diluent pipetted with the sample, and extreme within-run variations in activity are possible. When plasma is used instead of serum for routine analyses, regular checks for platelet contamination should be performed as a quality-control procedure, especially by laboratories separating plasma with bench-top centrifuges. Platelets can also interfere optically with assay of other enzymes and metabolites.     

Evaluation of lidocaine resistance in man using intermittent large-dose infusion techniques

Twelve patients with stable ventricular ectopic beats, nine with apparent resistance to lidocaine, were each studied with multiple intermittent large-dose lidocaine infusions that were started when ectopic beats were at peak frequencies and discontinued when either suppression or toxicity appeared. Of the nine patients with apparently resistant arrhythmias, three had arrhythmias, that were responsive at blood levels within the usual therapeutic range, four had arrhythmias refractory to lidocaine at usual blood levels but responsive at high blood levels, and two patients manifested toxicity without suppression of arrhythmia. Persisting ventricular arrhythmia during lidocaine therapy most often results from mechanical interference with the intravenous infusion route or from errors in drug administration. When these factors are excluded, there is a spectrum of patients who manifest various degrees of refractoriness to lidocaine.     

Influence of pH on in vitro disintegration of phosphate binders

Hyperphosphatemia, a common complication in patients with end-stage renal disease, is treated with oral phosphate-binding medications that restrict phosphorus absorption from the gastrointestinal (GI) tract. Impaired product performance, such as failure to disintegrate and/or dissolve in the GI tract, could limit the efficacy of the phosphate binder. Disintegration may be as important as dissolution for predicting in vitro product performance for medications that act locally on the GI tract, such as phosphate binders. Furthermore, patients with end-stage renal disease have a wide range in GI pH, and pH can influence a product's performance. The purpose of this study was to determine the effect of pH on in vitro disintegration of phosphate binders. Fifteen different commercially available phosphate binders (seven calcium carbonate tablet formulations, two calcium acetate tablet formulations, three aluminum hydroxide capsule formulations, and three aluminum hydroxide tablet formulations) were studied using the United States Pharmacopeia (USP) standard disintegration apparatus. Phosphate binders were tested in simulated gastric fluid (pH 1.5), distilled water (pH 5.1), and simulated intestinal fluid (pH 7.5). Product failure was defined as two or more individual tablets or capsules failing to disintegrate completely within 30 minutes. Results indicate that 9 of the 15 phosphate binders tested showed statistically significant differences in disintegration time (DT) based on pH. The percentage of binders that passed the disintegration study test in distilled water, gastric fluid, and intestinal fluid were 80%, 80%, and 73%, respectively. The findings of this study show that the disintegration of commercially available phosphate binders is highly variable. The pH significantly affected in vitro disintegration in the majority of phosphate binders tested; how significantly this affects in vivo performance has yet to be studied.