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Biomedical subjects

C E Johnson

Publications and source records attributed to C E Johnson.

At least 127 records · Page 7Linked to original sources

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging.

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.

Brain↗

Aerosol corticosteroids for the treatment of asthma.

In an effort to maximize the efficacy of corticosteroid treatment in asthma and minimize the adverse reactions, steroid therapy has evolved to the inhalation route of administration with aerosol compounds having potent topical antiinflammatory activity and minimal systemic effects. Corticosteroids exhibiting these properties that are available in the U.S. include beclomethasone dipropionate, triamcinolone acetonide, and flunisolide. The success or failure of patient response to orally inhaled corticosteroids is often a function of adequate drug delivery rather than the efficacy of the drug itself. Patients who cannot use the inhaler accurately may benefit from the use of a spacer or reservoir device. The three aerosolized corticosteroids have specific pharmacologic differences; however, none of these differences has translated into a clinically significant advantage or disadvantage of one product over the others. These agents should be considered for adjunctive therapy in patients whose asthma is not adequately controlled by beta-agonist bronchodilators, theophylline, or cromolyn sodium.

Adrenal Cortex Hormones↗

Compatibility of premixed theophylline and methylprednisolone sodium succinate intravenous admixtures.

The stability of theophylline supplied as a premixed injection and of methylprednisolone sodium succinate in admixtures containing both drugs was studied. Solutions containing theophylline in concentrations of 4.0 mg/mL and 0.4 mg/mL were used. Methylprednisolone sodium succinate was added to each solution to produce a final concentration of 0.5 mg/mL and 2.0 mg/mL of methylprednisolone alcohol, a pharmacologically active form of methylprednisolone sodium succinate. Each admixture was prepared in triplicate, and samples were kept at room temperature in glass containers. Immediately after admixture and at 3, 6, 12, and 24 hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol content. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The addition of theophylline in 5% dextrose injection to the methylprednisolone sodium succinate solutions resulted in decreased pH values for all solutions, which did not vary significantly throughout the study period. Theophylline concentrations did not change significantly compared with baseline. In solutions containing theophylline 0.4 mg/mL with either 2.0 or 0.5 mg/mL of methylprednisolone sodium succinate, less than 90% of the initial methylprednisolone sodium succinate concentrations remained at 24 hours. However, within three hours after admixture preparation, methylprednisolone alcohol was detected in those solutions in increasing concentrations. A commercial preparation of premixed theophylline in 5% dextrose injection in a concentration of 4 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2 mg/mL or less and administered intravenously within 24 hours after mixing.

Chromatography, High Pressure Liquid↗

Objective diagnosis of otitis media in early infancy by tympanometry and ipsilateral acoustic reflex thresholds.

Otitis media in early infancy carries a high risk of recurrent otitis media and prolonged middle ear effusion. To fulfill the need for objective diagnostic methods in this age group, we investigated susceptance tympanograms and ipsilateral acoustic reflex thresholds in infants younger than 5 months of age. Tympanometry and acoustic reflex thresholds were performed with an otoadmittance meter using a 660 Hz probe tone. Tympanograms were interpreted using quantitative measures. These findings were compared with independent otoscopic diagnoses in 67 ears with middle ear effusion and 69 ears that were effusion free. Diagnoses were confirmed by tympanocentesis when clinically indicated. There was excellent agreement among otoscopy, peak tympanogram susceptance, and ipsilateral acoustic reflex thresholds (kappa 0.82 to 0.86, agreement 91% to 93%). We conclude that susceptance tympanograms and ipsilateral acoustic reflex thresholds are accurate diagnostic tests for otitis media in infants younger than 5 months of age.

Acoustic Impedance Tests↗

A randomized controlled trial of amoxicillin plus clavulanate compared with cefaclor for treatment of acute otitis media.

We performed a randomized controlled trial of amoxicillin plus clavulanate versus cefaclor for treatment of acute otitis media. Total daily doses given in three divided doses were 40 mg/kg amoxicillin plus 10 mg/kg clavulanate, and 40 mg/kg cefaclor. Pathogens were eradicated from the middle ear exudate after 3 to 6 days of therapy in 35 (97%) of 36 patients given amoxicillin-clavulanate compared with 24 (75%) of 32 given cefaclor (P = 0.028). When analysis was restricted to patients with positive urine or serum drug assays during therapy, pathogens were eliminated in 33 (97%) of 34 patients given amoxicillin-clavulanate compared with 21 (75%) of 28 given cefaclor (P = 0.026). Bacterial isolates associated with bacteriologic failure of cefaclor therapy were Streptococcus pneumoniae (two patients), beta-lactamase-negative Haemophilus influenzae (four), and beta-lactamase-positive Branhamella catarrhalis (two). The single failure with amoxicillin-clavulanate therapy was associated with non-beta-lactamase-producing H. influenzae isolated from the middle ear exudate. We conclude that cefaclor is less efficacious than amoxicillin-clavulanate for the treatment of acute otitis media.

Acute Disease↗

Immunohistologic detection of estrogen receptors in paraffin-embedded breast cancers: correlation with cytosol measurements.

Paraffin-embedded sections of 76 human breast tissue specimens were analyzed for estrogen receptors (ER) and endogenous bound estrogen (ER-E). Preincubation of sections with polyestradiol phosphate was followed by stabilization of the complex with glutaraldehyde. The bound hormone was then visualized by the peroxidase-antiperoxidase (PAP) technique with antiestradiol as the primary antiserum. Normal breast tissue and benign proliferations were consistently positive for ER and ER-E. All specimens were examined for free and bound receptors in cytoplasm and nuclei. Among the carcinomas examined, a high correlation was found between the presence of ER by the PAP method and by the biochemical analysis of cytosol preparations. The PAP method, requiring no special preparation of surgical specimens, overcomes many of the disadvantages of the cytosol method and adds the advantage of independent evaluation of nuclear and cytoplasmic estrogen binding sites.

Breast Neoplasms↗

Platelet activation during exercise induced asthma: effect of prophylaxis with cromoglycate and salbutamol.

Peak expiratory flow (PEF) and plasma concentrations of platelet factor 4 and beta thromboglobulin were measured before and after exercise in nine asthmatic patients and 12 non-asthmatic volunteers. Exercise was preceded by administration in random order of either placebo, salbutamol 200 micrograms, or sodium cromoglycate 2 mg from a pressurised inhaler. In control subjects there were minimal changes in PEF and plasma concentrations of platelet factor 4 and beta thromboglobulin. In the asthmatic patients the typical changes in PEF were seen on exercise; plasma concentrations of platelet factor 4 and beta thromboglobulin rose significantly in parallel, the rise preceding the fall in PEF. The changes in peak flow and platelet activation induced by exercise were attenuated by prior administration of salbutamol or cromoglycate. These results indicate that exercise induced asthma is associated with a rise in platelet release products similar to that observed in antigen induced asthma.

Adult↗

Compatibility of aminophylline and methylprednisolone sodium succinate intravenous admixtures.

The stability of aminophylline and methylprednisolone sodium succinate in admixtures containing both drugs was studied. Admixtures containing aminophylline 1.0 mg/mL and methylprednisolone sodium succinate 2.0 and 0.5 mg/mL were prepared in both 5% dextrose injection and 0.9% sodium chloride injection. Each admixture was prepared in triplicate and samples were kept at room temperature in glass. Immediately after admixture and at one, two, and three hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline concentration and for both methylprednisolone sodium succinate and methylprednisolone alcohol. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The admixtures had higher pH values after aminophylline was added, but pH of the samples did not change significantly. Aminophylline concentrations did not change significantly throughout the study period. In 0.9% sodium chloride admixtures with methylprednisolone sodium succinate 0.5 mg/mL, less than 90% of the initial methylprednisolone concentration remained at two hours at the 2.0 mg/mL initial concentration, less than 90% remained at three hours. However, methylprednisolone alcohol (a pharmacologically active form of methylprednisolone sodium succinate) was detected in increasing concentrations after the first hour. Aminophylline in a final concentration of 1.0 mg/mL or less can be mixed with methylprednisolone sodium succinate in a final concentration of 2.0 mg/mL or less in 5% dextrose injection or 0.9% sodium chloride injection and administered intravenously within three hours after mixing.

Aminophylline↗

Renal ultrasound evaluation of urinary tract infections in children.

Ultrasonography of the kidney may replace the intravenous pyelogram as the study of choice in identifying treatable abnormalities in children with urinary tract infection. In a series of 64 consecutive children with urinary tract infection in whom an intravenous pyelogram, renal ultrasound, and voiding cystogram were performed, only one treatable abnormality (calyceal dilation) was identified by intravenous pyelogram, and it was not detected by ultrasound. Eleven children showed vesicoureteral reflux on the cystogram. In an additional 43 children in whom intravenous pyelogram was done only if the ultrasound or cystogram were abnormal, there were five abnormal cystograms. Four treatable abnormalities were identified by ultrasound, and there were confirmed by the intravenous pyelogram. Ultrasound should replace the intravenous pyelogram in children with a normal cystogram because of its accuracy, safety, and high patient acceptance. We have also documented a significant volume increase with acute infection in one or both kidney(s) of those children having upper urinary tract infection. Fifteen of 18 children with upper urinary tract infection had volume increases of 30% or more in at least one kidney; whereas only four of 21 children with lower urinary tract infection had increases of greater than 30% (P less than .005). Ultrasound volume measurements provide a new, noninvasive method for identifying the probable site of urinary tract infection.

Body Weight↗

Administrating incompatible drugs by a retrograde intravenous infusion system.

Use of a retrograde infusion system for concurrent intravenous administration of two incompatible drugs separated by a barrier fluid was studied. Four different barrier fluids (5% dextrose injection, 10% dextrose injection, 0.9% sodium chloride injection, and sterile water for injection) were used to separate sodium bicarbonate and calcium chloride. The primary infusion was 5% dextrose injection. The delivery system was visually inspected for formation of precipitate (calcium carbonate) upon addition of the two drug solutions and 2 ml of the barrier fluid. If precipitation occurred, the procedure was repeated, increasing the volume of barrier fluid incrementally until no precipitate could be seen. If no precipitate was seen with the initial 2 ml of barrier fluid, the volume of barrier fluid was decreased until precipitation occurred. These procedures were repeated for each barrier fluid at flow rates of 5-20 ml/hr for 90 minutes. The minimum volume of barrier fluid needed to prevent precipitate formation was determined in triplicate at each flow rate. The minimum volume of barrier fluid that prevented precipitate formation was approximately 2.0 ml. This volume did not differ significantly by barrier solution type or by flow rate. Sodium bicarbonate and calcium chloride can be administered concurrently by the retrograde intravenous method without visual incompatibility when separated by greater than or equal to 2 ml of barrier fluid, and this method can probably be used for administration of other potentially incompatible drugs.

Bicarbonates↗

Cimetidine-theophylline interaction: effects of age and cimetidine dose.

Influences of cimetidine dose and age on the cimetidine-theophylline interaction were evaluated. Group Y consisted of nine young adults, aged 22-35 years, and Group O of nine elderly adults, aged 60-74 years. Each subject completed three study phases in this randomized crossover study. During Phase A, oral dosing of 5 mg/kg theophylline was followed by 14 serial blood samples drawn over 36 h. Phases B and C involved the same procedures, but with oral cimetidine treatment of either 200 or 300 mg every 6 h, respectively. Theophylline pharmacokinetic parameters for Group Y, Group O, and Groups Y + O were calculated. Analyses of variance (ANOVA) for crossover design were performed for each variable. Intragroup interphase ANOVA results were interpreted using multiple range tests (Tukey's Q). Comparisons between groups were performed using two-sided Student's t tests (alpha = 0.05). Within each phase, the area under the concentration-time curve (AUC), elimination half-life (t1/2 el), clearance (Clp), and volume of distribution (Vd) of theophylline for the elderly subjects were not significantly different from those of the younger adults. Mean changes in AUC, t1/2 el, and Clp between Phases A and B for both Groups Y and O were highly significant (29.2 vs. 40.4, 36.7 vs. 44.8, and 25.9 vs. 29.8%, respectively). Further significant changes in those parameters were associated with 1.2 g/day of cimetidine (Phase C). Alterations of theophylline pharmacokinetics by cimetidine appear to be dose-related and are of similar magnitude in elderly and young healthy adults.

Administration, Oral↗

A randomized controlled trial of cefaclor compared with trimethoprim-sulfamethoxazole for treatment of acute otitis media.

We performed a randomized controlled trial of cefaclor administered twice daily compared with trimethoprim-sulfamethoxazole (TMP-SMZ) administered twice daily for the treatment of acute otitis media. Pathogens were eradicated from the middle ear exudate after 3 to 6 days of therapy in 35 of 37 (95%) patients given TMP-SMZ compared with 28 of 40 (70%) given cefaclor (P = 0.017). Haemophilus influenzae was eliminated in 13 of 14 (93%) patients given TMP-SMZ compared with 10 of 18 (56%) given cefaclor (P = 0.047). Clinical outcomes failed to distinguish between patients given TMP-SMZ or cefaclor. Symptoms improved despite persistent infection in 11 of 13 (85%) patients; middle-ear effusion persisted after therapy in 38 of 61 (62%) patients despite eradication of pathogens. We conclude that twice daily TMP-SMZ is more efficacious than twice daily cefaclor for the treatment of acute otitis media and that clinical outcomes may fail to detect differences between antibacterial agents in comparative drug trials in acute otitis media.

Acute Disease↗

Bacterial contamination of pressurized inhalers.

The objective of this project was to determine the incidence, location, and potential transmission of bacteria from pressurized inhalers contaminated during normal use by pediatric patients. Patients' inhaler usage and cleaning patterns also were evaluated. Fifteen inhalers from 12 children were cultured at three separate sites: the mouthpiece, spray portal, and the spray itself. The patient and/or parent were interviewed to determine usage and cleaning patterns. No bacterial growth was found from any of the cultured sites or aerosol of the control inhalers. All of the mouthpieces and portals of the patient-used inhalers were positive for growth, which is significant (p less than 0.01). One patient-used inhaler was positive for bacterial growth from the aerosol, which is not significant (p greater than 0.05). These results demonstrate that despite inhaler contamination, bacteria are not significantly transmitted by the aerosol. Routine cleaning of inhalers to remove accumulated debris is recommended to prevent disruption of drug delivery.

Aerosols↗

Antagonism of Ca2+-induced constriction of isolated rabbit ear artery by nitrendipine in high K+- and/or norepinephrine-containing medium.

Nitrendipine is a Ca2+ channel antagonist with vasodilator and antihypertensive properties. In the present experiments, the isolated rabbit ear artery was perfused with Ca2+-free Krebs-bicarbonate solution. Constriction of the artery was induced by addition of Ca2+ to perfusion fluid in the presence of KCl (75 mM, high K+), norepinephrine (NE) at various concentrations, or high K+ and NE. Nitrendipine produced concentration-dependent inhibition of the constrictor response to Ca2+ in high K+ medium. NE, added to high K+ medium, reversed the inhibitory effect of nitrendipine. In NE-containing medium, nitrendipine also inhibited the constrictor effect of Ca2+. Nitrendipine-induced inhibition was inversely proportional to the concentration of NE in the medium. The inhibitory effect of nitrendipine in the medium containing high K+ and NE was significantly less pronounced than in normal K+- and NE-containing medium. The experiments demonstrate relative resistance of "receptor-operated" channels to nitrendipine and suggest that under depolarizing conditions these channels may operate more effectively.

Animals↗

Stability of theophylline in human serum and whole blood.

The effect of various storage conditions on serum theophylline results using a fluorescence polarization immunoassay (FPI) method was studied. Two human subjects received sufficient oral theophylline to produce low and high therapeutic serum theophylline concentrations. Aliquots of venous whole blood (without anti-coagulant) and serum from each subject were sealed in polypropylene plastic and glass containers and stored at 4 degrees C and 25 degrees C. Additional aliquots of serum from each subject were stored in glass and polypropylene containers at -20 degrees C. FPI assays were performed on days 0 and 3 for room temperature serum samples, days 3 and 7 for refrigerated serum samples, and days 3, 7, 14, 28, 56, 168, and 336 for frozen serum samples. All whole blood samples were assayed on day 3 after removal of the clot. Some samples were tested using FPI for 1,3-dimethyluric acid, a metabolite of theophylline, and results from spiked samples and samples tested with high-pressure liquid chromatography were compared with FPI results to determine cross-reactivity of the metabolite. No appreciable change in the assayed theophylline values occurred under any storage temperature, nor was there any difference in results from samples stored in glass versus polypropylene containers. At a concentration of 20 micrograms/ml, 1,3-dimethyluric acid produced a cross-reactivity of 3.5% with the FPI system. The FPI method is not affected by storage of samples under the specified conditions over the time period studied.

Adult↗

Compatibility of paraldehyde with plastic syringes and needle hubs.

The compatibility of paraldehyde with plastic syringes and needle hubs was evaluated. Paraldehyde, USP, was stored in three types of 5-ml syringes: Plastipak, Glaspak, and all glass; the latter type served as the control. At specified times up to 24 hours, the contents of the syringes was evaporated to constant weight, and the residue was weighed. To evaluate the effect of paraldehyde on plastic needle hubs, needles with plastic and metal hubs were immersed in paraldehyde for 24 hours, and the paraldehyde was evaporated. No measurable change in residue weight was noted in any syringes for up to three hours. Compared with the control, there was a significant increase in the average weight of residue in the Glaspak and in the Plastipak syringes at 6, 12, and 24 hours. There was no significant difference in the weight of residue between the Glaspak and Plastipak syringes at those times, however. The amount of residue for the plastic and metal needle hubs was not significantly different. The source of the extractive residue appeared to be the rubber plunger tip. Since the nature of the extractive material in the residue is not known, paraldehyde should be administered in all-glass syringes if possible; other syringe types can be used only if the drug is administered immediately. The use of needles with plastic hubs is acceptable.

Acetaldehyde↗