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R C Cohn

Publications and source records attributed to R C Cohn.

10 recordsLinked to original sources
PubMed1992

In vitro antimicrobial activity of amiloride analogs against Pseudomonas.

The effects of specific amiloride analogs on Na+ channel and Na+/H+ antiport function in eukaryotic cells have been well studied, but the effect of these agents on Pseudomonas is unknown. The antimicrobial activity of benzamil HCl, 5-(N-N-dimethyl)amiloride HCl (DMA), 5-(N,N-hexamethylene)amiloride HCl (HMA), and 5-(N-methyl-N-isobutyl)amiloride HCl (MIA) on 30 Pseudomonas strains (20 P. aeruginosa and 10 P. cepacia) were compared to amiloride HCl after a 24-hour incubation in Mueller-Hinton broth at 35 degrees C. At pH 7.3 the MIC range and MIC50 (in mg/l; MIC50 in parentheses) for amiloride HCl, benzamil HCl, DMA, HMA and MIA were 400 to > 800 (> 800), 200 to 800 (400), 200 to > 800 (400), 100 to 400 (200), and 100 to 400 (200), respectively, for P. aeruginosa and > 800 (> 800), 400 to > 800 (800), 400 to > 800 (800), 200 to 800 (200), and 200 to 800 (200), respectively, for P. cepacia. Alteration of pH from 5.5 to 8.5 had a slight effect on potency. We conclude that all the analogs studied were more potent antipseudomonal agents in vitro than amiloride, with the more lipophilic compounds HMA and MIA, having the most profound activity.

Amiloride↗
PubMed1990

Sinusitis.

Explore the source record for details and available documents.

Bronchopulmonary Dysplasia↗
PubMed1989

Tracheal compression and the innominate artery: MR evaluation in infants.

Magnetic resonance (MR) imaging offers a noninvasive method of evaluating the mediastinum in infants with suspected compression of the trachea by the innominate artery. MR imaging was performed in 17 infants and children, aged 3-29 months, who had obstructive airway symptoms and who had undergone flexible fiberoptic tracheobronchoscopy. MR and endoscopic findings correlated in all cases but one. Of the remaining 16 patients, eight had endoscopic and MR evidence of tracheal compression at the level of the innominate artery, and eight had a normal upper thoracic trachea. In both groups, the innominate artery was situated anterior and to the left of the trachea with no difference in anatomic relationships. Measurements of the anteroposterior and transverse dimensions of the upper part of the mediastinum and the thymus failed to disclose significant differences between the two groups. Follow-up examinations of three patients showed decreasing tracheal compression without changes in tracheal-arterial relationships. This investigation disclosed no evidence of excessive mediastinal crowding. The findings support previous angiographic observations indicating that anterior tracheal compression is not due to an anomalous position of the innominate artery. Symptoms of tracheal compression may result from an intrinsic deficiency of the tracheal cartilage rather than an anatomic abnormality of the mediastinum or its vasculature.

Airway Obstruction↗
PubMed1989

The effect of sodium on amiloride-tobramycin synergy in Pseudomonas cepacia.

Amiloride combined with subinhibitory concentrations of tobramycin is synergistic against Pseudomonas cepacia in vitro. It is known that amiloride blocks transmembrane sodium (Na+) flux in eukaryotic cells, but the mechanism of action in bacteria is unknown. Amiloride-mediated Na+ gradient changes might affect transcellular tobramycin transport, resulting in synergy between these two drugs. To examine this hypothesis, we studied the effect of extracellular [Na+] on amiloride-tobramycin synergy with a reference strain of P. cepacia. Control growth in Mueller-Hinton broth (MHB) alone, MHB supplemented with 200 mmol/L NaCl, and MHB dialyzed against a Na+-free solution was determined by absorbance at 650 nm over 3 hours. Inhibition in the presence of amiloride, tobramycin, or a combination was expressed as percentage of control growth. Growth in the presence of tobramycin alone was significantly higher in MHB + NaCl than in MHB or dialyzed MHB (81% +/- 5%; vs 57% +/- 5%; 35% +/- 4%; mean +/- SEM, respectively, p = 0.003). Growth in the presence of amiloride alone was not significantly different in the three media (84% +/- 4%; 80% +/- 3%; 80% +/- 1%; respectively, p = 0.746). Percent control growth was significantly lower when the two drugs were combined, but results were not statistically different among the three media (3.5% +/- 3%; 0.2% +/- 0.8%; 4% +/- 1%; respectively, p = 0.604). We conclude that growth inhibition of P. cepacia in the presence of tobramycin is antagonized by increasing extracellular [Na+]. This antagonistic effect of [Na+] is reversed by amiloride. Changes in [Na+] do not appear to directly affect amiloride-tobramycin synergy in P. cepacia.

Amiloride↗
PubMed1988

Safety and efficacy of flexible endoscopy in children with bronchopulmonary dysplasia.

Because concern has been raised about the efficacy and safety of flexible fiberoptic bronchoscopy (FFB) in pediatric patients with chronic cardiopulmonary disorders, we reviewed the results of 129 flexible endoscopies performed on 47 children with a history of bronchopulmonary dysplasia (BPD) at our institution over a 44-month period. Indications for FFB; weight and age of the patient; and procedure format, including medication usage, findings, specimen results, and complications, were analyzed. Evaluation of previously diagnosed subglottic stenosis and airway abnormalities were the two most common indications (33% and 32%, respectively). Persistent or recurrent infiltrates or atelectasis, need for cultures, stridor, failure to extubate, hoarseness, and persistent wheeze were also cited. Endoscopic diagnoses included adenoidal hypertrophy, laryngomalacia, vocal cord abnormalities, interarytenoid membrane, subglottic stenosis, granulomas, tracheobronchomalacia, stenosis, obstruction, generalized inflammation/edema, polyps, tracheal bronchi, and anomalous bronchial anatomy. Cytomegalovirus, pneumococcus, nontypeable Haemophilus influenzae, Pseudomonas, or mixed gram-negative flora were isolated from some patients without tracheostomy. Minor complications (transient bradycardia, mild nasopharyngeal bleeding, and mild worsening of upper airway obstruction) occurred in 3.1% of procedures, but no severe complications occurred. Management was directly affected by procedure results in 41% of procedures. We concluded that the FFB can be a safe, useful procedure in the management of children with BPD.

Bronchial Diseases↗
PubMed1988

In vitro activity of amiloride combined with tobramycin against Pseudomonas isolates from patients with cystic fibrosis.

The diuretic amiloride has been under recent investigation as adjunctive therapy for pulmonary disease in children with cystic fibrosis (CF). In preliminary studies, the antimicrobial activity of this agent alone or combined with beta-lactam agents against reference strains of Pseudomonas aeruginosa and P. cepacia was poor; however, amiloride was markedly synergistic with tobramycin against P. cepacia. The purpose of this study was to determine the extent of amiloride-tobramycin synergy against CF respiratory isolates of P. aeruginosa, P. cepacia, and P. maltophilia. The MICs of tobramycin and amiloride alone against the Pseudomonas test strains were determined by agar dilution. Synergy was determined by combining each of four subinhibitory concentrations of amiloride (at least fourfold below the MIC) with doubling dilutions of tobramycin and comparing the MIC of tobramycin alone and in combination for each strain. At the highest concentration tested, the drug combination synergistically inhibited 50% of the P. cepacia strains tested; the combination was synergistic against fewer isolates of P. aeruginosa and P. maltophilia. Only P. cepacia was inhibited by tobramycin combined with amiloride at achievable airway concentrations. We conclude that the combination of tobramycin and amiloride may be potentially useful in the treatment of P. cepacia infections in children with CF.

Amiloride↗
PubMed1988

Phosphoinositide content of erythrocyte membranes in cystic fibrosis.

Phosphoinositide content was measured in erythrocyte membranes from 11 patients with cystic fibrosis (CF) and from 12 control subjects to determine whether altered levels of phosphatidylinositol-4-phosphate (Ptdlns4P) or phosphatidylinositol-4,5-bisphosphate (Ptdlns(4,5)P2) are responsible for the decrease in Ca2+-adenosine triphosphatase (Ca2+-ATPase) activity in this disorder. Isolated membranes were extracted with an acidified chloroform-methanol solvent system. The recovered lipids were separated by one-dimensional thin-layer chromatography and quantified with a colorimetric assay for phosphorus. The results are expressed in molar percent, moles of phosphoinositide times 100 divided by the total number of moles of phospholipid per membrane. The means +/- SEM of Ptdlns(4,5)P2, Ptdlns4P, and phosphatidylinositol (Ptdlns) in CF membranes (1.07 +/- 0.18, 1.02 +/- 0.22, and 2.32 +/- 0.36 molar percent, respectively) were indistinguishable from controls (0.91 +/- 0.14, 0.85 +/- 0.12, and 2.21 +/- 0.32 molar percent, respectively) (P greater than 0.20 for all three pairs). The accuracy of quantitative recovery throughout the procedure was determined by adding a radioactive internal standard, L-3-phosphatidyl[2-3H]inositol to 10 membrane preparations. Although quantitative recoveries, as determined by percent radioactivity recovered, varied from 54% to 92%, mean Ptdlns(4,5)P2, Ptdlns4P, and Ptdlns levels appropriately corrected from tracer loss were still indistinguishable between the two groups. We conclude that absolute phosphoinositide levels are not altered in cystic fibrosis erythrocyte membranes and that the differences in Ca2+-ATPase activity cannot be explained on this basis.

Cystic Fibrosis↗
PubMed1978

Purification of human renal renin.

1. Human renal renin has been purified 200 000-fold from cadaver kidney cortex by a method which employs affinity chromatography on aminohexyl peptstatin. 2. The product of this purification has a specific activity of 400 Goldblatt units/mg when compared with Haas human renin standard. 3. This product appears as a single band on sodium dodecyl sulphate gel and polyacrylamide-disc gel electrophoresis. Renin enzymatic activity was recovered after elution from a polyacrylamide-disc gel run at pH 7.8. 4. Yield with this method was 1%.

Chromatography, Affinity↗