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Biomedical subjects

C E Johnson

Publications and source records attributed to C E Johnson.

At least 19 recordsLinked to original sources
PubMed1995

Pathophysiology and treatment of alpha 1-antitrypsin deficiency.

The pathophysiology of alpha 1-antitrypsin (AAT) deficiency and the use of alpha 1-proteinase inhibitor therapy in the management of emphysema caused by AAT deficiency are described. AAT deficiency is the most common genetic cause of liver disease in children and emphysema in adults. However, not all patients with AAT deficiency develop hepatic or pulmonary involvement. Changes in the composition of the AAT molecule have been associated with AAT dysfunction in liver disease, whereas lung disease occurs when AAT concentrations are reduced. A definitive diagnosis can be made through serum AAT phenotype determination. Therapy for liver disease induced by AAT deficiency consists of supportive measures. Therapy for pulmonary disease due to AAT deficiency includes AAT augmentation therapy along with supportive measures. The available product, alpha 1-proteinase inhibitor, is derived from fractionated plasma and has similar biological activity to native serum AAT. Clinical trials have demonstrated a positive effect on serum and lung concentrations of AAT with few adverse events. Two recombinant forms of AAT have also been developed; however, few trials have been published evaluating their safety and efficacy in AAT-deficient patients. Many questions remain unanswered concerning AAT deficiency and replacement therapy. AAT augmentation therapy appears to reduce the progression of emphysema in some AAT-deficient patients.

Clinical Trials as Topic↗
PubMed1995

Resolution of middle ear effusion in newborns.

OBJECTIVES: To determine the natural history of middle ear effusion (MEE) in newborns and compare the results of pneumatic otoscopy with tympanometry and acoustic reflex measurements in the evaluation of the middle ear of neonates. DESIGN: A descriptive natural history study with comparison of three evaluation methods for MEE. SETTING: County hospital nursery and pediatric clinic. PARTICIPANTS: Sixty-eight full-term, healthy neonates were studied on day 1 of life; 65 on day 2; and 24 on day 3. Thirty-eight infants returned at 2 weeks of age, and from this group, 23 returned at 2 months of age. INTERVENTIONS: Two independent observers performed otoscopy. An audiologist performed tympanometry and ipsilateral acoustic reflex measurements. Infants were evaluated daily from birth by all three methods for up to 3 days. MAIN OUTCOME MEASURE: The time to resolution of MEE as determined by three methods. RESULTS: In the first 3 hours of life, all babies examined had MEE diagnosed in both ears. By the third day, MEE apparently had resolved in 73% of ears by otoscopy, 88% by acoustic reflex measurements, and 92% by tympanometry. At 2 weeks, MEE was present by otoscopy in 13% (10/75 of ears). These were primarily newly acquired MEEs. Interobserver agreement by otoscopy as determined by kappa scores was moderate on days 1 and 3, poor on day 2, and excellent at 2 weeks and 2 months. CONCLUSIONS: Middle ear effusion diagnosed by otoscopy apparently resolves in 72 hours in most neonates. Interobserver agreement of otoscopists was excellent after babies were discharged from the nursery, suggesting that pneumatic otoscopy can be used to diagnose MEE in neonates this age. Most MEEs that are diagnosed 2 weeks and 2 months after birth are new and asymptomatic.

Acoustic Impedance Tests↗
PubMed1995

Continuous versus intermittent nebulized terbutaline: plasma levels and effects.

The purpose of this investigation was to compare continuous versus intermittent nebulization of a beta 2-agonist, terbutaline, to determine whether differences exist in plasma concentrations or adverse cardiovascular effects of the drug with these two techniques for its administration. Sixteen children 6 to 16 yr of age, admitted for acute asthma, were enrolled in this randomized double-blind clinical trial. Nebulization of 16 mg of terbutaline over an 8-h period was performed either continuously or intermittently, with a dose of 4 mg given over 20 min every 2 h. The peak plasma terbutaline concentration for the intermittent nebulization treatment (INT) group (5.1 +/- 2.1 ng/ml) occurred 1 h after the fourth inhalation treatment and was similar to the peak concentration for the continuous nebulization treatment (CNT) group, which was reached at the end of the 8 h period (4.7 +/- 2.3 ng/ml). The maximum heart rate increase for the INT group (19.6 +/- 18.3 bpm) occurred 1 h after the fourth dose and was similar to the peak observed in the CNT group (19.6 +/- 19.2 bpm), which occurred after 3 h. Similar increases in systolic and decreases in diastolic pressures were observed for the INT and CNT groups. No evidence of serious adverse myocardial complications was seen in either group, as evidenced by measurements of the MB fraction of creatine phosphokinase (CPK-MB) and Holter-monitor recordings. Continuous nebulization of the terbutaline produces similar plasma concentrations and cardiovascular physiologic responses as intermittent nebulization.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

Stability of isradipine in an extemporaneously compounded oral liquid.

The stability of isradipine in an extemporaneously compounded oral liquid was studied. A suspension was prepared from the powder of commercially available 5-mg isradipine capsules and sufficient Simple Syrup, NF, to make a final volume of 50 mL. A control suspension was prepared from analytical-grade isradipine powder and Simple Syrup, NF. The final concentration of isradipine in both suspensions was 1 mg/mL. Three identical volumes of each suspension were stored in 2-oz amber glass prescription bottles, which were stored at 4 degrees C. Immediately after preparation and at 7, 16, 22, 28, and 35 days, samples were visually inspected and assayed in duplicate by high-performance liquid chromatography; the pH of the samples was also determined. At least 95% of the initial isradipine concentration remained throughout the study period in all samples of both suspensions. Color, odor, and pH did not change appreciably. Isradipine 1 mg/mL in an oral liquid compounded from Simple Syrup, NF, and powder from capsules was stable for at least 35 days in amber glass bottles at 4 degrees C.

Administration, Oral↗
PubMed1994

Stability of ganciclovir sodium and amino acids in parenteral nutrient solutions.

The stability of ganciclovir sodium and amino acids in parenteral nutrient solutions was studied. Three admixtures of ganciclovir sodium plus parenteral nutrient solution were prepared, one containing ganciclovir sodium 0.83 mg/mL, 1% amino acids, and 10% dextrose injection; one containing ganciclovir sodium 1.4 mg/mL, 2.5% amino acids, and 10% dextrose injection; and one containing ganciclovir sodium 1.4 mg/mL, 5% amino acids, and 25% dextrose injection. The solutions were visually inspected for precipitates, color change, and gas formation and were tested for pH. High-performance liquid chromatography was used to measure the concentration of ganciclovir and 16 amino acids in each admixture immediately and one, two, and three hours after preparation. There was no evidence of visual incompatibility in any of the admixtures, and pH did not vary appreciably during the study. The mean ganciclovir sodium concentration remaining was greater than 100% of the initial concentration for all the admixtures at one, two, and three hours. The mean amino acid concentration remaining in the admixtures with 2.5% or 5.0% amino acids was greater than 90% of the initial concentration for each amino acid at one, two, and three hours. The mean amino acid concentration remaining in the admixture with 1% amino acids was greater than 90% of the initial level at one and two hours. Ganciclovir sodium 0.83 mg/mL was stable for at least three hours in parenteral nutrient solution with 1% amino acids, and ganciclovir sodium 1.4 mg/mL was stable for at least three hours in admixtures with 2.5% or 5% amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1994

Measles vaccine immunogenicity in 6- versus 15-month-old infants born to mothers in the measles vaccine era.

HYPOTHESIS: The low titer of measles antibody in infants of mothers with vaccine-induced immunity may allow immunization against measles before 15 months of age. METHODS: Six- and 15-month-old infants born to mothers < or = 30 years of age with no history of measles were recruited. Infants enrolled at 6 months of age were immunized with monovalent measles vaccine (Attenuvax), and maternal serum and infant pre- and postvaccination sera were obtained. Those enrolled for primary vaccination at 15 months of age received either Attenuvax (N = 12) or M-M-RII (N = 3). Six-month-old infants were revaccinated with M-M-RII at 15 months of age; pre- and postrevaccination sera were again obtained. Three antibody assays were used: a measles neutralizing assay (NT) and two enzyme immunoassays (EIA) for measles IgG and measles IgM. RESULTS: Among primary vaccinees, 14 of 19 infants aged 6 months (74%) developed NT antibody, as did 15 of 15 infants aged 15 months (100%). The reciprocal geometric mean titer of 6-month-old seroresponders was 23.3, significantly lower than that of the 15-month-old primary vaccinees (87.7, P < .001). Primary seroconversion rates by EIA were 53% for 6-month-old infants and 100% for those aged 15 months. Revaccination of infants who had received Attenuvax at 6 months of age resulted in 100% NT positivity; the geometric mean titer rose to equal that of the group given primary immunization at 15 months of age. Measles IgM antibody was detected in 10 of 14 infants tested 1 month after primary vaccination at 15 months, but was not detected in any of the revaccinated infants after the second dose at 15 months of age (P < .001). CONCLUSIONS: 1) Immunization with measles vaccine in infants born to vaccine-immune mothers at 6 months of age induced NT antibody in 74% of infants. 2) Revaccination of prior 6-month-old vaccinees at 15 months resulted in antibody titers equivalent to 15-month-old vaccinees. 3) Lack of an IgM response following revaccination suggests that even seronegative infants may be primed to respond on re-exposure to measles.

Adult↗
PubMed1993

The role of bacterial adhesins in the outcome of childhood urinary tract infections.

OBJECTIVES: To compare the efficacy of 3-day vs 10-day treatment with a combination of amoxicillin and clavulanate potassium for children with uncomplicated urinary tract infections and to determine the role of host factors, including vesicoureteral reflux, and of bacterial virulence factors, including adhesins, in treatment outcome. DESIGN: Randomized, double-blind, controlled trial. SETTING: A pediatric infectious diseases clinic at an urban medical center. PATIENTS: Thirty-seven children with uncomplicated urinary tract infections. INTERVENTIONS: Treatment with 3 days or 10 days of antibiotics at a dosage of 20 mg/kg per day of amoxicillin and 5 mg/kg per day of clavulanate potassium in three divided doses. MEASUREMENTS AND MAIN RESULTS: The success rate for 10-day treatment was 82% (14/17) compared with 55% (11/20) for 3-day treatment (P = .09). Among the 35 patients infected with Escherichia coli, all 10 patients infected with adhesin-negative isolates were treated successfully regardless of the duration of treatment, whereas only 14 (56%) of the 25 infections involving adhesin-positive isolates were clinically cured (P = .015). Two of the three failures in the 10-day treatment group were in patients with reflux. CONCLUSIONS: We conclude that 3-day treatment with amoxicillin and clavulanate is insufficient for afebrile childhood urinary tract infections and that both bacterial and host factors affect treatment outcome.

Adhesins, Escherichia coli↗
PubMed1993

A convincing case for primary repair of penetrating colon injuries.

Over the past 14 years, 146 patients with penetrating colon trauma were managed by primary repair with/without resection (PR, n = 55), and by diverting colostomy (DC, n = 91). These groups did not differ in terms of age, ISS (Injury Severity Scale), PATI (Penetrating Abdominal Trauma Index), a-AIS (abdominal Abbreviated Injury Scale), or preoperative hypotension. No intergroup differences were manifested in intra-abdominal complications (fistula/leak, abscess, pancreatitis, intestinal obstruction, wound dehiscence). The percentage of patients who experienced at least one major intra-abdominal complication did not differ statistically when the two groups were compared--12.7% in PR versus 11% in DC--although risk in both groups increased with the additional number of organs injured. Wound infection was significantly higher (p < 0.05) in the PR group (19.6%) compared with the DC group (9.4%). Mortality in the PR and DC groups was 0% and 3.6%, respectively. One hundred and ten patients who underwent elective colostomy closure following trauma had a 9.1% intra-abdominal complication rate and a 3.6% wound infection rate. These risks should be considered when colostomy is selected to manage patients with penetrating colon injury. These data support primary repair of all colon injuries, reserving skin closure for patients with limited collateral damage.

Adult↗
PubMed1993

Bacterial polysaccharide immune globulin for prophylaxis of acute otitis media in high-risk children.

We evaluated the prevention of recurrences of acute otitis media (AOM) by bacterial polysaccharide immune globulin (BPIG), a hyperimmune human immune globulin prepared by immunizing donors with bacterial polysaccharide vaccines. We used a randomized, stratified, double-blind, placebo-controlled design. Children < or = 24 months of age with 1 to 3 prior episodes of AOM received BPIG, 0.5 ml/kg, or saline placebo intramuscularly at entry and 30 days later. During the 120-day follow-up period, AOM was diagnosed by using clinical criteria and was confirmed with tympanocentesis and culture of the middle ear exudates. Eighty-eight episodes of AOM were observed in 76 patients who completed the study. The incidence of AOM during the entire 120-day study period was similar in BPIG and placebo recipients. Pneumococcal AOM was significantly less frequent in BPIG recipients (0.21 episode per patient) than in placebo recipients (0.45 episode per patient; p = 0.05). Time spent free of AOM was significantly prolonged in recipients of BPIG, in comparison with placebo recipients (51 vs 35 days; p = 0.034). This study demonstrated that circulating antibody, even without stimulation of specific local immunity, may prevent infection of the middle ear. The use of immune globulin preparations for longer periods or at a higher dosage might decrease the incidence of recurrent AOM in otitis-prone children, and deserves further evaluation.

Acute Disease↗
PubMed1993

Stability of an extemporaneously compounded baclofen oral liquid.

The stability of baclofen in an extemporaneously compounded oral liquid formulation for 35 days was studied. A suspension was prepared by grinding commercially available 20-mg baclofen tablets and adding Glycerin, USP, to form a paste. Simple Syrup, NF, was added as necessary to make a final volume of 60 mL. A control solution was prepared from analytical-grade baclofen powder in Simple Syrup, NF. The final concentration of baclofen in both formulations was 5 mg/mL. Three samples of each preparation were stored in 2-oz, amber glass prescription bottles in the dark under refrigeration at 4 degrees C. Immediately after preparation and at 7, 14, 21, 28, and 35 days, samples were visually inspected, tested for pH, and assayed in duplicate by high-performance liquid chromatography. On day 35, the mean percentages of the initial baclofen concentrations remaining were 95.9% in the suspension and 95.6% in the solution. The color, odor, and pH of the samples did not change appreciably over the study period. In an extemporaneously compounded oral liquid preparation in Simple Syrup, NF, stored in the dark under refrigeration, baclofen was stable for at least 35 days.

Administration, Oral↗
PubMed1992

Altered steady-state levels of the messenger RNAs for c-myc and p53 in L1210 cell lines resistant to deoxyadenosine.

L1210 cell lines, selected for resistance to deoxyadenosine due to the loss of allosteric inhibition of ribonucleotide reductase by dATP, had altered steady-state levels of the mRNAs for c-myc, fos, and p53. Wild-type L1210 cells had constitutive steady-state levels of c-myc and p53 with little or no fos mRNA. Two different deoxyadenosine-resistant cell lines (Y8 and ED2) had elevated steady-state levels of c-myc and fos but essentially no p53 mRNA. Hydroxyurea-resistant L1210 cells had the same levels of c-myc, fos, and p53 as the wild-type cells. There was no amplification of the gene for c-myc in the Y8 or ED2 cell lines. The half-life for c-myc mRNA was essentially the same in the wild-type and the Y8 and ED2 cells. Nuclear runoff experiments showed that the rates of transcription for c-myc in the Y8 and ED2 cells were elevated and could account for the increased steady-state levels of c-myc in these two cell lines. The transcription rate for p53 mRNA was not decreased in the Y8 and ED2 cells and therefore did not account for the loss of the steady-state levels of p53 in the cells. Cycloheximide treatment of the Y8 and ED2 cells resulted in a marked increase in the steady-state p53 mRNA level, indicating that a protein which was rapidly turned over was responsible for the extremely short half-life of p53 mRNA in these two cell lines.

Animals↗
PubMed1992

The accuracy of antenatal ultrasonography in identifying renal abnormalities.

OBJECTIVE: To determine the accuracy of measuring antenatal renal pelvic diameter for prediction of renal abnormalities. RESEARCH DESIGN: Prospective evaluation of all pregnant women undergoing ultrasonography. SETTING: A teaching hospital providing primary and referral maternity care. PARTICIPANTS: Fifty-six pregnant women with suspected fetal hydronephrosis or cystic lesions identified from 7500 ultrasonograms over 3 years. METHODS: Antenatal renal pelvic diameter was measured in the anteroposterior dimension. Neonates underwent postnatal ultrasonography after day 3 of life; if the results were abnormal, a cystogram and renal diuretic scan were obtained. RESULTS: None of 50 kidneys 15 mm or smaller in anteroposterior pelvic diameter had obstruction; 11 (79%) of 14 kidneys larger than 15 mm were obstructed or demonstrated vesicoureteral reflux. Of 12 kidneys believed to be multicystic before birth, five (42%) proved to have hydronephrosis. CONCLUSIONS: Since the majority of fetuses with suspected hydronephrosis proved to be normal, parents should not be unduly alarmed by the physician. Renal pelvic diameter of more than 15 mm is strongly predictive of hydronephrosis. Since severe hydronephrosis is treatable and can be mistaken for a multicystic kidney antenatally, full radiologic evaluation is needed soon after birth.

Congenital Abnormalities↗
PubMed1992

Measuring the comparative efficacy of antibacterial agents for acute otitis media: the "Pollyanna phenomenon".

In randomized, double-blind trials of antibiotic therapy for acute otitis media that determined both clinical and bacteriologic outcomes, clinical success rates were (93%) 236 of 253 for patients with bacteriologic success, (62%) 25 of 40 for those with bacteriologic failure, and (80%) 124 of 155 for those with nonbacterial acute otitis media. These rates were used to calculate the effectiveness of three strategies for assessing drug efficacy: (1) tympanocentesis and culture before and during therapy (bacteriologic efficacy), (2) tympanocentesis before therapy and assessment of clinical efficacy in bacterial acute otitis media, and (3) no tympanocentesis and assessment of clinical efficacy in clinical (total) acute otitis media. For a drug with a bacteriologic efficacy of 100%, calculated clinical efficacy was 93% for bacterial acute otitis media and 89% for clinical acute otitis media. For a drug with bacteriologic efficacy of 27%, a rate consistent with no antibacterial therapy, efficacy was 71% for bacterial acute otitis media and 74% for clinical acute otitis media. We conclude that if efficacy is measured by symptomatic response, drugs with excellent antibacterial activity will appear less efficacious than they really are and drugs with poor antibacterial activity will appear more efficacious than they really are. The predominant phenomenon is that drugs with poor antibacterial activity will appear to be clinically effective in the treatment of acute otitis media.

Acute Disease↗
PubMed1992

Abnormal cardiovascular responses induced by localized high power microwave exposure.

A hypothesis of microwave-induced circulatory under perfusion was tested in ketamine anesthetized rats whose heart rate, mean arterial pressure, pulse pressure, respiration rate, and body temperatures were monitored continuously. Fifty-eight ventral head and neck exposures in a waveguide consisted of sham-exposure and exposure to continuous wave (CW) and pulsed 1.25 GHz microwaves for 5 min. The 0.5 Hz (10 microseconds, 2 W average) and 16 Hz (1 microsecond, 6.4 W average) pulse-modulated microwaves were delivered at 400 kW peak power. The CW microwaves were 2 and 6.4 W. The average specific absorption rate was 4.75 W/kg per watt transmitted in the brain and 17.15 W/kg per watt transmitted in the neck. Respiration rate and mean arterial pressure were not altered. Changes in heart rate and pulse pressure were observed in rats exposed to higher power (16 Hz pulses and 6.4 W CW) but not to the lower average power microwaves (0.5 Hz pulses and 2 W CW). Depression of pulse pressure, an indication of a decrease in stroke volume, and increased (tachycardia) or decreased (bradycardia) heart rate were noted in presence of whole-body hyperthermia. The cardiac output of those animals exposed to higher average power microwaves was considered to be below normal as hypothesized. Decreased cardiac output and normal mean arterial pressure resulted in an increase in the total peripheral resistance which was contrary to the anticipated thermal response of animals.

Animals↗