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Biomedical subjects

D G Johnson

Publications and source records attributed to D G Johnson.

At least 145 records · Page 8Linked to original sources

Bronchodilator activity of a nonxanthine phosphodiesterase inhibitor; 2,4-diamino-5-cyano-6-bromopyridine (compound I).

The ability of 2,4-diamino-5-cyano-6-bromopyridine (compound 1) to inhibit bronchiolar smooth muscle constriction was examined in isolated rings of rabbit primary bronchi and intrapulmonary bronchioles. After carbachol-induced constriction these tissue were significantly relaxed by either compound I or 1-methyl-3-isobutylxanthine (MIX) in a similar dose-dependent manner with 50 to 80% relaxation occurring at 100 microM of either compound. Compound I also attenuated the constrictor response of bronchial rings to histamine and significantly reduced the tension generated by horseradish peroxidase in sensitized tissues responding to this antigen. In addition, both compound I and MIX were found to inhibit the soluble cyclic AMP phosphodiesterase activity of rabbit bronchioles. Finally, both compound I and MIX caused a nearly 2-fold, time-dependent increase in cyclic AMP levels in isolated rabbit intrapulmonary bronchioles. The similarities of both the in vitro tissue responses to these compounds and the phosphodiesterase inhibitory properties suggest that the ability of compound I to reduce constrictor-induced tension generation in bronchial smooth muscle is related to the inhibition of cyclic nucleotide phosphodiesterases and the consequent elevation of cyclic AMP.

1-Methyl-3-isobutylxanthine↗

Integrated imaging of neonatal renal masses.

Thirty-three neonatal renal masses were evaluated during a 2-year interval. The final diagnoses in these 33 patients were hydronephrosis [14], multicystic dysplastic kidney [10], renal vein thrombosis [3], obstructed upper pole duplication [2], polycystic kidney disease [2], nephroblastomatosis [1], and mesoblastic nephroma [1]. We recommend an integrated imaging approach that utilizes sonography to clarify anatomy and renal scintigraphy or excretory urography to determine renal function.

Female↗

Intraoperative measurement of maxillary repositioning: an ancillary technique.

A technique for measuring maxillary movement with the LeFort I osteotomy is described. Three-dimensional measurement of upper jaw position can be gauged to within 1 mm by means of a simple two-point measurement system. When used in combination with direct bone measurements and appropriate surgical sequencing, assessment of maxillary repositioning is possible at virtually any time during the surgical procedure.

Cephalometry↗

Value of tests for evaluation of gastroesophageal reflux in children.

The accuracy of five tests for the diagnosis of gastroesophageal reflux in children was performed in 93 symptomatic children with gastroesophageal reflux and 16 nonreflux patients. These tests include the barium esophagram, the Tuttle test, extended esophageal pH monitoring, esophagoscopy, and esophageal biopsy. Esophagoscopy was less sensitive in detecting reflux in patients than any other test (P = less than 0.001), and biopsy was more likely to identify reflux patients than the barium swallow (P = less than 0.02), but there was no test superior to others. The severity of esophagitis noted at endoscopy or the presence of eosinophils or neutrophils in the mucosa was not associated with a decreased possibility that one other test would be normal or that surgical repair of the reflux would be performed. Patients with extended esophageal pH test scores markedly elevated were less likely to have another negative test (P = less than 0.01) and more likely to have surgical repair of gastroesophageal reflux (P = less than 0.001). Obtaining two tests of esophageal function that agree increases the certainty of diagnosis, and use of several tests are indicated if the results of a single test do not support the clinical impression.

Adolescent↗

Current thinking on the role of surgery in gastroesophageal reflux.

Gastroesophageal reflux is common in infants and children. In most cases it causes little more than inconvenience and remits spontaneously with time and maturation. A small and select group of refluxing children, however, will develop complications of reflux severe enough to justify operative control when medical treatment fails. Recurrent pulmonary infections, obstructive apnea, nutritional wasting, and progressive inflammatory injury to the esophagus all qualify as surgical indications, provided a reasonable cause-effect relationship with reflux can be established. The procedure of choice depends very much upon the skill and experience of the surgeon. The complete fundoplication seems to offer more complete control of reflux, but it has the potential for more frequent and more complicated side-effects.

Barium Sulfate↗

2,4-Diamino-5-cyano-6-halopyridines: a new class of cyclic AMP phosphodiesterase inhibitors with therapeutic potential.

2,4-Diamino-5-cyano-6-halopyridines have been described previously as oral insulinotropic agents and have been found recently to have bronchodilatory properties. In the present report the synthesis of the iodo compound is newly described, and it is established that HI- or HBr-mediated condensation and cyclization of malononitrile in 1,2-dichloroethane yield selectively the 5-cyanopyridine derivatives. The pyridine derivatives were found to constitute a new class of potent cyclic AMP phosphodiesterase inhibitors. Inhibition of purified dog kidney cyclic AMP phosphodiesterase was of the mixed type. Since cyclic AMP phosphodiesterase inhibitors are known to enhance glucose-induced insulin secretion and to activate glucose production by the liver, the finding that the pyridine derivatives described here inhibited cyclic AMP phosphodiesterase opens new avenues of interpretation for their insulinotropic action as well as for the paradoxical lack of improvement of glucose disposal by elevation of insulin after oral drug administration. Cyclic AMP phosphodiesterase inhibition also has the potential of explaining the bronchodilatory effects of these drugs.

3',5'-Cyclic-AMP Phosphodiesterases↗

Bronchoscopic removal of aspirated foreign bodies in children.

Foreign body aspiration is the cause of death in over 500 children per year in the United States. Tracheobronchial inhalation of foreign bodies may result in acute respiratory distress, chronic pulmonary infections, atelectasis, or death. A review of 262 children ranging from 4 months to 13 years of age was undertaken to identify factors important in diagnosis to illustrate the effectiveness of newer endoscopic techniques and equipment, and to evaluate results and complications. Coughing, choking, and wheezing were the presenting symptoms seen in 91 percent of the patients. Inspiratory and expiratory chest radiographs were positive in 81 percent of the 224 children with foreign bodies removed. Fluoroscopy was positive in 41 patients, 88 percent of whom had foreign bodies removed. Bronchoscopy is required for treatment, and with experience, this procedure can be simple and safe. Ninety-nine percent of foreign bodies identified at bronchoscopy were removed successfully. Minor complications occurred in 8 percent of the patients, and there were no deaths.

Adolescent↗

Gastro-oesophageal reflux and respiratory disease: the place of the surgeon.

The association between gastro-oesophageal reflux (GER) and respiratory disease is well studied and established. A causal relationship, except in the case of clear cut aspiration, continues to elude proof but is supported by an increasing body of clinical experience. Barium oesophagram is the logical first test to demonstrate reflux, to rule out distal obstruction, and to provide good imaging of the oesophagus. Extended (24 h) oesophageal pH monitoring has proven to be the most reliable test in our hands for the identification of abnormal reflux. The false negative rate with this test was 12%, and false positives were seen only 6% of the time. Radionuclide scintigraphy offers the theoretical possibility for absolute correlation between reflux and aspiration, but in practice the results have been disappointing. Where other treatment measures have failed and where objective tests and clinical evidence point to the probability that respiratory disease is reflux-induced, anti reflux surgery is justified and most often strikingly successful. A Nissen fundoplication with a loose wrap and a short cuff is still the standard treatment for antireflux surgery. Long term follow-up suggests the benefits of antireflux surgery outweigh the occasional complications and side effects where operation is performed to control otherwise intractable reflux-associated symptoms.

Child, Preschool↗

Ga-67 uptake in the lung in sarcoidosis.

Images were obtained with Ga-67 and bronchopulmonary lavage performed in 21 patients with sarcoidosis (31 studies). The Ga-67 index, a semiquantitative criterion, was compared to a quantitative computer index based on lung:liver activity ratios; accuracy in predicting active alveolitis (defined by lavage lymphocyte counts) was assessed and differences between 24- and 48-hour studies examined. Computer activity ratios correlated well with the Ga-67 index, which had a sensitivity of 64%, specificity of 71%, and accuracy of 68% compared to 71%, 82%, and 77%, respectively, for the computer scores. Scores at 24 and 48 hours were similar. These results suggest that (a) Ga-67 scanning is useful in staging activity in pulmonary sarcoidosis, (b) quantitative computer scores are accurate in predicting disease activity, and (c) scanning can be performed 24 or 48 hours after injection.

Adult↗

Effect of exposure to low temperature on normal and iron-deficient subjects.

Twenty-one Venezuelan peasants were segregated into three groups on the basis of measurements of iron status: seven normal subjects, six iron-deficient subjects with normal hemoglobin and eight iron-deficient subjects with a hemoglobin concentration of less than 9 g/dl. All subjects were placed in a water bath at an initial temperature of 36 degrees C. The water temperature was then rapidly lowered to 28 degrees C, and observations were made over the period of 1 h. Mean oral temperature of the first group fell 0.2, the second group 0.5, and the third group 0.9 degrees C. Mean plasma norepinephrine levels in both groups of iron-deficient subjects were significantly higher at 36 degrees C and during cold exposure compared with control subjects. Oxygen consumption was also significantly increased in both groups of iron-deficient subjects after cold exposure.

Adult↗

Hypoxemia increases plasma catecholamine concentrations in exercising humans.

To determine whether plasma catecholamine concentrations (a measure of sympathetic nervous activity [SNA]) rise above normoxic levels during exercise with hypoxemia, we exercised seven men for 15 min at three loads that required from 40 to 88% of maximal O2 uptake (VO2max). Subjects breathed room air on one day and 11-12% O2 on another with relative work loads corrected for the 24% fall in VO2max during hypoxemia. Hypoxemia caused large increments in norepinephrine (NE) concentration (radioenzyme technique) to 1.21 +/- 0.20 ng/ml (mean +/- SE), 2.79 +/- 0.38, and up to 5.90 +/- 0.75 (hypoxemia) compared with 0.89 +/- 0.06, 1.66 +/- 0.16, and 3.95 +/- 0.39 in normoxia at the three loads, respectively (P less than 0.001). Epinephrine (E) concentration approximately doubled (P less than 0.001) in hypoxemia at each load when compared with normoxic levels (i.e., 0.10 +/- 0.01 ng/ml, 0.23 +/- 0.03, and 0.46 +/- 0.06 in normoxia). However, hypoxemia did not significantly alter linear relationships between log plasma NE concentration and either heart rate (HR) or percent VO2max utilized, or between HR and percent VO2max. Thus NE concentration, like HR, appeared to reflect relative severity of exercise and overall SNA in both hypoxemia and normoxia. Above 40% VO2max during hypoxemia, circulating NE and E far exceeded levels known to have direct vasoconstrictor and metabolic effects in normoxic humans, but hypoxemia may blunt vasoconstriction in some regions.

Adult↗

Bone and liver images in medullary carcinoma of the thyroid gland: concise communication.

Thirty-four patients with surgically documented medullary carcinoma of the thyroid (MCT) and elevated serum calcitonin levels had Tc-99m phosphate bone and/or Tc-99m sulfur colloid liver images for suspected metastases. Liver images demonstrated metastatic lesions in nine of 32 patients (28%). Bone images were positive for metastases in eight of 30 patients (27%). Four of these eight abnormal bone studies detected only skeletal lesions, two demonstrated only extraosseous metastases, and two showed both kinds. Of 18 patients with both radionuclide bone studies and skeletal radiographs, four demonstrated skeletal metastases, and lesions were recognized on both examinations. This study demonstrates that radionuclide bone and liver images frequently detect metastatic lesions in patients with MCT and elevated serum calcitonin levels, and that some nonskeletal metastases in patients with this tumor display an unusual affinity for bone-seeking radiotracers.

Adolescent↗

Long-term follow-up of surgery for gastroesophageal reflux in infants and children.

Surgery for gastroesophageal reflux in infants and children has been shown to be safe and effective, but long-term results of the surgery have not been investigated. Because studies in adults show objective evidence of recurrent reflux five years postoperatively, we recalled 25 children for long-term follow-up of surgery. The preoperative symptoms of vomiting, apnea, pneumonia, and hematemesis were permanently controlled in all patients. Failure to thrive was reversed in all patients except those with multiple malformations. Extended esophageal pH monitoring revealed only one patient with symptomatic recurrent reflux. As a group, the children had significantly less reflux as measured by extended pH monitoring than did controls. Thirty-six percent of patients had mild to moderate symptoms of gas bloat. Thirty-two percent were described as very slow to finish most meals. Twenty-eight percent were unable to burp or vomit. Twenty-five percent choked on some solids. These symptoms did not correlate with the type of operation performed. Long term outcome of antireflux surgery in children is better than in adults.

Airway Obstruction↗

Ketoconazole inhibition of testicular secretion of testosterone and displacement of steroid hormones from serum transport proteins.

In vivo perfusion of canine testes with ketoconazole inhibited the stimulation of testosterone production by human chorionic gonadotropin in a dose-dependent manner. Ketoconazole also selectively displaced steroids from serum-binding globulins. Dihydrotestosterone and estradiol binding to sex hormone-binding globulin were inhibited by ketoconazole. Cortisol binding to corticosteroid-binding globulin was unaffected. The concentrations of ketoconazole that inhibited human chorionic gonadotropin stimulation of testicular androgen production and displaced sex steroids from sex hormone-binding globulin were in the range of blood levels found in patients on higher therapeutic dosage regimens. Suppression of testicular testosterone synthesis and displacement of estrogens from sex hormone-binding globulin may decrease the androgen/estrogen ratio of the blood and contribute to the development of gynecomastia that has been reported in some ketoconazole-treated patients.

Animals↗