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Biomedical subjects

E W Larson

Publications and source records attributed to E W Larson.

At least 19 recordsLinked to original sources

Disulfiram treatment of patients with both alcohol dependence and other psychiatric disorders: a review.

In treatment of alcohol dependence, disulfiram is most useful in conjunction with a structured, supervised, aftercare program. However, it has been reported to cause psychiatric side effects and to interact with various psychiatric medications. Many patients with alcohol dependence suffer from other psychiatric disorders and are treated with such psychiatric medications. This paper reviews the pertinent clinical pharmacology of disulfiram and the literature on potential psychiatric complications and drug interactions of disulfiram. At the usual dosage, about 250 mg/day, disulfiram does not appear to increase significantly the risk of psychiatric complications or of psychiatric drug interactions. Therefore, it can be considered a treatment option for patients with alcohol dependence and other psychiatric disorders.

Alcoholism

Structure-antinociceptive activity of neurotensin and some novel analogues in the periaqueductal gray region of the brainstem.

Neurotensin, an endogenous tridecapeptide, produces a potent, naloxone-insensitive antinociceptive response when it is microinjected into the periaqueductal gray region of the rat brainstem. In the present study, the ED50 for neurotensin in inducing antinociception was 1.5 nmol, two times more potent than morphine. We sought to find whether neurotensin's antinociceptive effects were mediated by the same receptor that mediates its other functions. We found that the structure-activity relationship of neurotensin-induced antinociception was different from that required for the stimulation of intracellular cyclic GMP production in neuroblastoma clone N1E-115 and the binding to N1E-115 cells, human brain tissue, or rat periaqueductal gray. These data suggest there exists a subtype of neurotensin receptors in neural tissue that mediates its antinociceptive actions.

Analgesics

Selectivity of antimuscarinic compounds for muscarinic receptors of human brain and heart.

Seven antimuscarinic compounds, used mostly for the treatment of extrapyramidal problems, were tested in vitro in radioligand binding assays for evidence of selectivity for two different pharmacological subtypes of the human muscarinic receptor, M1, a predominant form in brain, and M2, a predominant form in heart. Although biperiden, scopolamine, procyclidine, and benztropine showed significant selectivity in the in vitro assays, it is likely that in clinical practice biperiden would be the drug of choice to avoid any antimuscarinic effects on the heart.

Brain

Development of type II pneumocytes in rat lung.

At a late stage of fetal development, the mammalian alveolar epithelium undergoes an abrupt differentiation as a part of the preparation of the lung for the postnatal demands of gas exchange. Some of the most striking changes occur in the type II pneumocytes as they lose their glycogen and start to produce the lamellated inclusion granules that contain pulmonary surfactant. Premature birth before adequate type II cell maturation results in the neonatal respiratory distress syndrome, which is frequently fatal. We have used serial ultrathin sectioning, electron microscopy, and three-dimensional reconstructions to study the ultrastructural features of maturation of rat type II cells from a single rat each at age gestational day 20 through adult stages. We found evidence over this time span for compartmentation of several secretory granule precursors within type II cells. Changes in the polarization of lamellar bodies were observed over the time period studied. We also found marked gestational changes in the number and morphology of type II cell cytoplasmic processes that perforate the basement membrane. Type II cell mitochondria changed in shape during postnatal development from single, spherical to complex, branched structures. Volume composition obtained from serial sections of a small number of type II cells agreed closely with published morphometric data, indicating that throughout the animal's lifespan, type II cells are a homogenous population.

Aging

Electrooculogram in central retinal vein obstruction.

The electrooculograms (EOGs) of 24 patients with central retinal vein obstruction (CRVO) were correlated with fundus appearance and with the electroretinogram (ERG) b/a wave ratio. Of the 24, 17 (70.8%) showed abnormal EOGs [light peak versus dark trough ratio (Lp/Dt) of less than 1.85]. The EOG Lp/Dt ratio was abnormal in 64.7%, although the ERG b/a ratio was within normal limits. Though the exact mechanism is still not entirely clear, the EOG became abnormal in most patients with CRVO and correlated well with the severity of the disease.

Adult

Cynomolgus monkey model for experimental Q fever infection.

A subhuman primate model was developed for study of the pathogenesis of infection with Coxiella burnetii. Cynomolgus monkeys (Macaca fascicularis) that were exposed to 10(5) mouse median infectious intraperitoneal doses of C. burnetii in a small-particle aerosol developed clinical signs of illness and pathologic changes characteristic of Q fever infection in humans. All monkeys had radiologic evidence of pneumonia by day 9. Antibodies to C. burnetii were detectable by the indirect fluorescent antibody test by day 7. These data indicate that the cynomolgus monkey is a suitable model for study of the pathogenesis of Q fever infection and may prove valuable in the evaluation of C. burnetii vaccines.

Aerosols

Cell-mediated immune responses of guinea pigs to an inactivated phase I Coxiella burnetii vaccine.

The ability of a killed phase I Coxiella burnetii vaccine to induce cell-mediated immune responses in guinea pigs was studied. Cell-mediated immune responses were assessed by the inhibition of macrophage migration and lymphocyte transformation assays. The macrophage migration response occurred rapidly and was detected at high levels, but was relatively short-lived. In contrast, the lymphocyte transformation response developed more slowly, and persisted for a longer period. The vaccine, given in a single dose or in two doses 1 week apart, protected guinea pigs from a subsequent virulent challenge.

Animals

Experimental Q fever infection in congenitally athymic nude mice.

Congenitally athymic nude (nu/nu) mice and their phenotypically normal (nu/+) euthymic littermates were exposed to Coxiella burnetii administered as small-particle aerosols. After challenge, both strains of mice became infected, as characterized by rickettsemia, viable rickettsiae in the spleen, and serological conversion. The major difference noted was that euthymic animals had cleared rickettsiae from peripheral circulation and the spleen within 14 days. In contrast, rickettsiae were detected and isolated from spleen and blood of athymic mice through 60 days.

Animals

Continuous aerosol therapy system using a modified Collison nebulizer.

A Collison nebulizer was incorporated into an exposure system for administering antiviral compounds as continuous aerosols to mice infected with influenza virus. The nebulizer was modified to control aerosol output by varying the liquid feed rate. A multiple regression equation was developed from data obtained with uranine dye to define the aerosol concentration of the dye in the system as a function of the concentration of the dye in the spray fluid and the rate at which it was aerosolized. The rate of change of the concentration of the test solution due to evaporative losses was also ascertained for a 1-ml/min feed rate over a 23.5-h period of operation. Procedures are outlined for using these relationships to determine the concentration of a given drug that will result in a given dose. Performance data for the drug ribavirin are presented.

Aerosols

Influenza virus population dynamics in the respiratory tract of experimentally infected mice.

Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar challenge. In all of the infections, the highest virus concentrations were observed in the lungs. Peak concentrations in the trachea were lower than in the lungs but higher than in the nasopharynx. Decreasing virus levels were observed by 120 h after challenge and were generally below detectable levels by the end of 10 days. A compartmental model of a single mathematical form was developed which provided close fits of the virus concentration measurements regardless of the challenge dose, site of initial deposition, or respiratory tissue considered. The model includes seven compartments with five associated rate parameters. The application of compartmental modeling techniques and expression of the virus population dynamics in mathematical terms is regarded as a new approach to the study of the pathogenesis of infections.

Administration, Intranasal