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Biomedical subjects

K Johnson

Publications and source records attributed to K Johnson.

At least 253 records · Page 14Linked to original sources

The effect of antihistamines on the laryngeal chemoreflex.

The laryngeal chemoreflex (LCR) consists of apnea, laryngospasm, and cardiovascular changes in neonates after laryngeal irritation and has been implicated in sudden infant death syndrome and apnea of infancy. Antihistamines attenuate a similar vagally mediated pulmonary chemoreflex. The intravenous antihistamine effect on the LCR was studied in neonatal piglets. Laryngeal muscle activity, respiration, blood pressure, and pulse were measured during water stimulation of the LCR. After baseline LCR recordings, intravenous diphenhydramine (2.5 mg/kg) or cimetidine (20 mg/kg) was bolused (control group received saline). LCR measurements were repeated over 7 hours. Diphenhydramine significantly shorted apneas (P < .05) 3 to 7 hours after drug bolus, which is believed to be secondary to central atropinic effects. Cimetidine demonstrated no attenuation of the LCR.

Administration, Intranasal↗

Improvement of gas exchange, pulmonary function, and lung injury with partial liquid ventilation. A study model in a setting of severe respiratory failure.

STUDY OBJECTIVE: To evaluate gas exchange, pulmonary function, and lung histology during gas ventilation of the perfluorocarbon-filled lung compared with gas ventilation of the gas-filled lung in severe respiratory failure. STUDY DESIGN: Application of gas (GV) or partial liquid (PLV) ventilation in lung-injured sheep. SETTING: A research laboratory at a university medical center. SUBJECTS: Eleven sheep 17.1 +/- 1.8 kg in weight. INTERVENTIONS: Lung injury was induced by intravenous administration of 0.07 mL/kg oleic acid followed by saline pulmonary lavage. When alveolar-arterial oxygen pressure difference (P[A-a]O2) was 600 mm Hg or more and PaO2 was 50 mm Hg or less with fraction of inspired oxygen of 1.0, bijugular venovenous extracorporeal life support (ECLS) was instituted. For the first 30 min on ECLS, all animals were ventilated with gas. Over the ensuing 2.5 h, ventilation with 15 mL/kg gas was continued without intervention in the control group (GV, n = 6) or with the addition of 35 mL/kg of perflubron (PLV, n = 5). MEASUREMENTS AND RESULTS: At 3 h after initiation of ECLS, Qps/Qt was significantly reduced in the PLV animals when compared with the GV animals (PLV = 41 +/- 13%; GV = 93 +/- 4%; p < 0.005). At the same time point, pulmonary compliance was increased in the PLV when compared with the GV group (PLV = 0.61 +/- 0.14 mL/cm H2O/kg; GV = 0.41 +/- 0.02 mL/cm H2O/kg; p < 0.005). The ECLS flow rate required to maintain the PaO2 in the 50 to 80 mm Hg range was substantially and significantly lower in the PLV group when compared with that of the GV group (PLV = 25 +/- 20 mL/kg/min; GV = 87 +/- 15 mL/kg/min; p < 0.001). Light microscopy performed on lung biopsy specimens demonstrated a marked reduction in lung injury in the liquid ventilated (LV) when compared with the GV animals. CONCLUSION: In a model of severe respiratory failure, PLV improves pulmonary gas exchange and pulmonary function and is associated with a reduction in pulmonary pathology.

Acute Disease↗

Triplet repeats in neuromuscular disorders.

SBMA, SCA1 and DM are all neuromuscular disorders which have very different presentation with varying degrees of severity but with a common feature of muscular weakness. In addition they all show anticipation correlating with the length of an unstable trinucleotide repeat. It is possible that trinucleotide repeat expansions will underlie other hereditary neuromuscular disorders, for example spinocerebellar ataxia type 2 (mapped to 12q and with similar symptoms to SCA1 including anticipation) is a prime candidate (30). The biochemical effects of these expansions have not yet been elucidated and therefore effective therapeutic interventions cannot currently be designed for affected individuals. However, the relative ease of diagnosis and the availability of accurate prenatal testing have already had a significant impact on the patient groups.

Female↗

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Delivery of Health Care↗

Fat embolism syndrome associated with asthma and sickle cell-beta(+)-thalassemia.

A 25-year-old African-American man with sickle cell-beta(+)-thalassemia presented with acute asthma of 2 days' duration. The asthma was well controlled by 48 hr, and parenteral medications were changed to oral bronchodilators and steroids. Sixty hours after presentation, he developed pain similar to that of sickle cell vaso-occlusion, for which he received small amounts of analgesics. He died approximately 84 hours after presentation. Autopsy showed extensive marrow necrosis and massive fat embolism. This is the first reported case of fat embolism syndrome associated with this genotype, the mildest of the clinically significant sickle cell hemoglobinopathies. The relationship between these etiologic factors and indications for transfusions are discussed.

Adult↗

Myotonic dystrophy patients have larger CTG expansions in skeletal muscle than in leukocytes.

The genetic basis of myotonic dystrophy is an unstable expansion of CTG repeats located in a gene on chromosome 19 that encodes a putative serine/threonine protein kinase. We studied the somatic mosaicism of the (CTG)n expansion in myotonic dystrophy patients. (CTG)n expansions were 2- to 13-fold greater in DNA isolated from skeletal muscle than in DNA from leukocytes in 10 of 11 patients with myotonic dystrophy. Different muscles of the same individual showed similar (CTG)n expansions. In postmortem tissues from an adult patient, (CTG)n expansions in brain, skeletal muscle, cardiac muscle, testes, and liver were all greater than in leukocytes. Normal myotonic dystrophy gene alleles from 7 healthy subjects had the same number of CTG repeats in leukocytes and muscle. The myotonic dystrophy mutation displays pronounced heterogeneity in somatic cells. The (CTG)n expansion observed in peripheral blood leukocytes is not necessarily representative of the repeat expansion in affected tissues, such as skeletal muscle and myocardium. In some patients with myotonic dystrophy, the predictive value of genetic analysis based on leukocyte DNA may be limited.

Adult↗

Spin trapping of azidyl and hydroxyl radicals in azide-inhibited rat brain submitochondrial particles.

Succinate-driven respiration in azide-inhibited rat brain submitochondrial particles (smps) produces azidyl and hydroxyl radicals that were detected by spin trapping with 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO). Production of radicals required succinate and oxygen and was eliminated by heat denaturation, which indicates that radical production is a result of respiration. The concentrations of both DMPO/.OH and DMPO/.N3 were decreased by addition of catalase to the smps, which indicates that H2O2 is involved in radical production. In the absence of azide anion, DMPO/.OH was not detected in the same system, even after five additions of succinate over a period of 24 h. It is proposed that azide inhibition of cytochrome c oxidase results in increased production of superoxide, which is efficiently converted to hydrogen peroxide by membrane-bound superoxide dismutase. Hydrogen peroxide activates endogenous peroxidase to react with azide anion forming azidyl radical, which damages the peroxidase, resulting in decreased production of azidyl radical with successive additions of succinate. Hydroxyl radical is produced from the hydrogen peroxide that is not removed by peroxidase. The increased production of superoxide in the azide-inhibited system suggests that loss of cytochrome c oxidase activity can lead to increased radical production if other proteins in the respiratory chain remain active. In the azide-inhibited system, reaction of azide anion with H2O2-activated endogenous peroxidase and spin-trapping of the resulting azidyl radical is a convenient monitor of H2O2 production.

Animals↗

Effects of marijuana on performance of a computerized cognitive-neuromotor test battery.

To evaluate the sensitivity of a computerized cognitive-neuromotor test battery in assessing the effects of marijuana (delta-9-tetrahydrocannabinol [THC]), we conducted a study of 10 healthy male volunteers who were experienced marijuana smokers. After extensive training on the performance tasks, each subject was tested on three separate days after smoking a cigarette containing either 1.75% THC, 3.55% THC, or placebo according to a randomized double-blind repeated measures design. Testing was carried out before smoking and 30, 90, and 150 minutes after smoking the cigarette. Of the five tasks employed, the digit-symbol substitution test with memory and the reaction time task were the measures most sensitive to effects of marijuana. We examined the usefulness of the coefficient of variation and effect size as indices of sensitivity to be used across different types of tasks.

Adult↗