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Biomedical subjects

J Frazer

Publications and source records attributed to J Frazer.

At least 19 recordsLinked to original sources

A controlled, prospective, 1-year trial of citalopram in the treatment of panic disorder.

BACKGROUND: The objective of this study was to evaluate the efficacy and tolerability of citalopram in the long-term treatment of adult outpatients with panic disorder with or without agoraphobia. METHOD: Patients in this double-blind, parallel-group trial were assigned to 1 of 3 fixed dosage ranges of citalopram (10 or 15 mg/day, 20 or 30 mg/day, or 40 or 60 mg/day), 1 dosage range of clomipramine (60 or 90 mg/day), or placebo. After the completed 8-week acute treatment period, the eligible patients could continue the treatment for up to 1 year. Of the 475 patients who were randomly assigned for the short-term trial, 279 agreed to continue double-blind treatment at their assigned doses. The primary efficacy measure used was the Clinical Anxiety Scale panic attack item, and the response was defined as no panic attacks (score of 0 or 1). The other key measures used were the Physician's Global Improvement Scale, the Patient's Global Improvement Scale, and the Hamilton Rating Scale for Anxiety (HAM-A). RESULTS: In all drug-treated groups, except the group receiving the lowest citalopram dose, the treatment outcome was generally better than with placebo. As determined by a life table analysis of response, the probability of response during the 12 months was significantly greater with all treatment regimens than with placebo (p < .05), with citalopram 20 or 30 mg/day demonstrating the best response. Panic attacks tended to disappear in all patients remaining in the study until the end of follow-up. Analysis of the difference in the number of patients in different treatment groups remaining in the study (perhaps the best measure of long-term efficacy) also demonstrated that the patients treated with citalopram in dosage ranges of 20 or 30 mg/day and 40 or 60 mg/day had better response than placebo-treated patients (p < .0002 and p < .004, respectively). HAM-A and Global Improvement Scale scores also showed that patients treated with active drug showed greater improvement than placebo-treated patients. All treatment groups showed no new or exceptional adverse event clusters. CONCLUSION: Citalopram in the dosage range of 20 to 60 mg/day is effective, well tolerated, and safe in the long-term treatment of patients who have panic disorder.

Adolescent↗

Acetylcholine: oscillation of levels in mouse brain following electroshock.

The acetylcholine contents of mouse brain regions were measured in order to investigate the response of cholinergic neurons to electroshock. In this study, mice were subjected to electroshock and then sacrificed by microwave irradiation at time intervals of from 0.4 to 6.9 a after electroshock. In all of the brain regions studied, the acetylcholine concentration appeared to oscillate with a mean period of approximately 2.5 a following electroshock. The rate of recovery of acetylcholine after electroshock was calculated for each brain region from the oscillatory equation obtained by nonlinear regression analysis of the experimental data. The rates of synthesis of acetylcholine derived from these in vivo measurements were substantially higher than have been indicated by other methods.

Acetylcholine↗

Whitefly transmission and efficient ssDNA accumulation of bean golden mosaic geminivirus require functional coat protein.

Bean golden mosaic geminivirus (BGMV) has a bipartite genome composed of two circular ssDNA components (DNA-A and DNA-B) and is transmitted by the whitefly, Bemisia tabaci. DNA-A encodes the viral replication proteins and the coat protein. To determine the role of BGMV coat protein systemic infection and whitefly transmission, two deletions and a restriction fragment inversion were introduced into the BGMV coat protein gene. All three coat protein mutants produced systemic infections when coinoculated with DNA-B onto Phaseolus vulgaris using electric discharge particle acceleration "particle gun." However, they were not sap transmissible and coat protein was not detected in mutant-infected plants. In addition, none of the mutants were transmitted by whiteflies. With all three mutants, ssDNA accumulation of DNA-A and DNA-B was reduced 25- to 50-fold and 3- to 10-fold, respectively, as compared to that of wild-type DNA. No effect on dsDNA-A accumulation was detected and there was 2- to 5-fold increase in dsDNA-B accumulation. Recombinants between the mutated DNA-A and DNA-B forms were identified when the inoculated coat protein mutant was linearized in the common region.

Animals↗

Eosinophil hematopoietins antagonize the programmed cell death of eosinophils. Cytokine and glucocorticoid effects on eosinophils maintained by endothelial cell-conditioned medium.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was established as the constitutive and elicited human umbilical vein endothelial cell-derived eosinophil viability-sustaining factor. Stimulation of endothelium cell monolayers with IL-1 alpha (5 U/ml) increased the 48-h elaboration of GM-CSF from a mean of 3.2 to a mean of 8.2 pM (P less than 0.05). Dexamethasone (100 nM) decreased the constitutive GM-CSF elaboration by 49% (P less than 0.001) but did not diminish production by IL-1 alpha-stimulated endothelium. However, eosinophil viability decreased by 21% in dexamethasone-pretreated IL-1 alpha-stimulated endothelial cell-conditioned medium (P less than 0.05), which suggested viability antagonism by glucocorticoids. After 24 h of culture, eosinophil viability for replicate cells in enriched medium alone or with 1 pM GM-CSF decreased from means of 43 and 75% to means of 21 and 54%, respectively, when dexamethasone was included (P less than 0.05). However, 10 pM GM-CSF, IL-3, or IL-5 protected the cells against dexamethasone and against endonuclease-specific DNA fragmentation. In this model system of eosinophil-tissue interactions, dexamethasone prevents the endothelial cells from inducing a pathobiologic phenotypic change in the eosinophil by suppression of GM-CSF elaboration to concentrations that are not cytoprotective. Cytokine priming by GM-CSF, IL-3, or IL-5 may account for the differential responsiveness of select eosinophilic disorders to glucocorticoids.

Cell Survival↗

Liposomes of enviroxime and phosphatidylcholine: definition of the drug-phospholipid interactions.

Interaction of the antiviral compound, enviroxime (E), with natural and synthetic phosphatidylcholines in organic and aqueous media was studied. Although insoluble in chloroform, E dissolved in chloroform solutions containing phosphatidylcholines. Solvation was directly related to the length of the fatty acid chains of the phospholipid. Proton spin resonance studies suggested an interaction of the fatty acid chains with the aromatic rings of E. Suspension of E-phosphatidylcholine mixtures of molar ratios up to 0.7:1.0 in aqueous media resulted in the formation of multilamellar liposomes. Liposomes containing E were more stable permeability barriers than those prepared with phospholipid alone, a property previously observed with cholesterol. Competition experiments suggested that E bound to the same sites in lipid bilayers as does cholesterol. These data indicate that E is incorporated into lipid bilayers of liposomes and that it alters the physical properties of the liposomes in a manner similar to that of cholesterol.

Benzimidazoles↗

Left ventricular aneurysm formation: an iatrogenic cause for the third mogul.

Two cases of left ventricular pseudoaneurysm formation developing post-operatively after mitral valve replacement are reported. The chest radiographs showed an abnormal protuberance on the left heart border at the site of the "third mogul". The definitive diagnosis of this protuberance, resulting from the development of a left ventricular aneurysm, was made on angiography in each case. This site is unusual for left ventricular aneurysm formation, with the exception of the annular subvalvular aneurysm described in the negro population. Relevant aetiological factors in the development of these post-operative left ventricular pseudoaneurysms are considered. Since pseudoaneurysms are more prone to rupture than true aneurysms, it is concluded that early diagnosis of development of these left ventricular pseudoaneurysms should be made.

Female↗

Proton NMR of human breast tumors: correlation with clinical prognostic parameters.

Proton NMR spectroscopy and imaging of human breast tissue have provided new methods in studying breast carcinomas. Continuous wave proton NMR spectroscopy in this study is able to discriminate breast carcinomas from normal breast tissue on the basis of the integrated area under the water and lipid peaks, width at half height of the water peak, and chemical shift of the lipid peak. In addition, the NMR parameters were correlated with the following clinical and pathologic prognostic indices: TNM tumor stage, nuclear grade, and estrogen receptor status (ER). Width at half height of the lipid peak (1/2 delta lipid) correlated with tumor content and ER. Studies using higher resolution proton or phosphorus NMR spectra may separate signals that can correlate with biological information on breast neoplasms useful to the clinician. Chemical shift of the lipid peak may be used to sharpen contrast on MRI of breast tumors.

Adenofibroma↗

Nuclear magnetic resonance assessment of adenosine triphosphate (ATP) dynamics in ischemic mouse livers perfused with adenine and ribose.

Hepatic energy stores are essential to liver viability. We used a mouse liver perfusion model and MR spectroscopy to study the effect of adding two precursors of ATP (adenine and ribose) on ATP dynamics during ischemia and reperfusion. Using Krebs-Henseleit buffer with or without added adenine and ribose made little difference in the ATP decay rate during ischemia, but the recovery of ATP during reperfusion was more complete when adenine and ribose were added to the buffer. These findings suggest that the addition of the precursors of ATP, adenine and ribose, to perfusate after ischemia can accelerate and enhance ATP recovery.

Adenine↗

Responses of Adaxial and Abaxial Stomata of Normally Oriented and Inverted Leaves of Vicia faba L. to Light.

Stomatal conductances of normally oriented and inverted leaves were measured as light levels (photosynthetic photon flux densities) were increased to determine whether abaxial stomata of Vicia faba leaves were more sensitive to light than adaxial stomata. Light levels were increased over uniform populations of leaves of plants grown in an environmental chamber. Adaxial stomata of inverted leaves reached maximum water vapor conductances at a light level of 60 micromoles per square meter per second, the same light level at which abaxial stomata of normally oriented leaves reached maximum conductances. Abaxial stomata of inverted leaves reached maximum conductances at a light level of 500 micromoles per square meter per second, the same light level at which adaxial stomata of normally oriented leaves reached maximum conductances. Maximum conductances in both normally oriented and inverted leaves were about 200 millimoles per square meter per second for adaxial stomata and 330 millimoles per square meter per second for abaxial stomata. Regardless of whether leaves were normally oriented or inverted, when light levels were increased to values high enough that upper leaf surfaces reached maximum conductances (about 500 micromoles per square meter per second), light levels incident on lower, shaded leaf surfaces were just sufficient (about 60 micromoles per square meter per second) for stomata of those surfaces to reach maximum conductances. This ;coordinated' stomatal opening on the separate epidermes resulted in total leaf conductances for normally oriented and inverted leaves that were the same at any given light level. We conclude that stomata in abaxial epidermes of intact Vicia leaves are not more sensitive to light than those in adaxial epidermes, and that stomata in leaves of this plant do not respond to light alone. Additional factors in bulk leaf tissue probably produce coordinated stomatal opening on upper and lower leaf epidermes to optimally meet photosynthetic requirements of the whole leaf for CO(2).

Journal Article↗

Effect of erythrocyte storage and oxyhemoglobin affinity changes on cardiac function.

Storage of blood can depress erythrocyte 2,3-diphosphoglycerate (DPG) levels and thereby increase oxyhemoglobin affinity and potentially decrease capillary-to-tissue oxygen transport. We measured myocardial function and metabolism in isolated rabbit hearts with fixed coronary flow under basal conditions and during isoproterenol stress at 37 and 30 degrees C, comparing high and low oxyhemoglobin affinity (OHA) erythrocytes. The high OHA state resulted from standard storage conditions, which caused depressed values of DPG and P50 (the oxygen tension at which hemoglobin is 50% saturated). The low OHA erythrocytes were initially stored and then underwent biochemical treatment to restore the DPG and P50 values to normal. The low OHA cells released more oxygen, and myocardial oxygen consumption and contractile function were increased relative to the high OHA cells during both the basal and stress states at both 37 and 30 degrees C. These observations may be relevant for patients with limited coronary flow when such patients receive large transfusions of stored blood.

Animals↗

The agglutination reactions of Haemophilus paraphrophilus and H. paraphrohaemolyticus, and some observations on the agglutination of H. Aphrophilus and H. haemoglobinophilus (H. canis).

Agglutination tests were used to study the surface antigens of two recently described species of the genus Haemophilus, H. paraphrophilus and H. paraphrohaemolyticus, and their antigenic relationship to other members of the genus. The results obtained with a few strains of H. haemoglobinophilus and H. aphrophilus are also reported. The species H. paraphrophilus appears to be homogeneous; no major cross-reactions were observed. The species H. paraphrohaemolyticus contains at least three serotypes, of which two have been defined in terms of agglutination reactions. Cross-agglutinations occurred between one strain of H. paraphrohaemolyticus and strains of the other V-dependent species, H. parainfluenzae and H. parahaemolyticus. Of the X-dependent species, H. haemoglobinophilus seems to be homogeneous, and the species H. aphrophilus is not. A non-specific antibody against horse blood in the medium occurred erratically and was present in only two antisera, those raised to H. aphrophilus strain Khairat and H. haemoglobinophilus strain no. NCTC8540.

Agglutination↗

The isolation of an X-dependent strain of haemophilus from otitis media identified as H. haemoglobinophilus (canis).

The growth factor requirements, together with the serological results, would seem to justify the view that strain M.G., isolated from a child, M.G., with otitis media, in pure culture has to be regarded as H. haemoglobinophilus (canis). It is interesting to note that two out of the three strains of H. haemoglobinophilus (canis) available in this laboratory agglutinate to a titre of 1:80 with the serum produced against H. aphrophilus, the only other X-dependent haemophilus we had used for the preparation of antiserum.

Agglutination↗