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Biomedical subjects

M Johnston

Publications and source records attributed to M Johnston.

At least 271 records · Page 15Linked to original sources
PubMed1984

Cumulative scales for the measurement of agoraphobia.

The questionnaire responses of 559 agoraphobic subjects were analysed to see whether there was a shared hierarchical pattern of fear and avoidance. The items were divided on the basis of a principal component analysis into 13 loading on an Agoraphobia factor and eight on a Claustrophobia factor. When analysed with Guttman Scaling Analysis valid cumulative scales were found for each factor. These scales were replicated in three independent cohorts of subjects and met the most stringent scaling requirements. The scales produced three valid scores of severity for each individual, the first describing exactly which Agoraphobic items the subject avoids, the second describing Agoraphobic items feared and the third Claustrophobic items avoided. Since it is possible to deduce the current pattern of fear and avoidance from the scores, they can be used to summarize the clinical state of an individual client or for making precise descriptive comparisons between agoraphobics . The scales also indicate that agoraphobics do not develop their own unique set of difficulties from the possible pool of problems, but acquire an ordered set of difficulties, the order being shared by other agoraphobics .

Adult↗
PubMed1984

Sequences that regulate the divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae.

The GAL1 and GAL10 genes of Saccharomyces cerevisiae are divergently transcribed, with 606 base pairs of DNA separating their transcription initiation sites. These two genes are stringently coregulated: their expression is induced ca. 1,000-fold in cells growing on galactose and is repressed by growth on glucose. The nucleotide sequence of the region of DNA between these genes and the precise sites of transcription initiation are presented here. The most notable feature of the nucleotide sequence of this region is a 108-base-pair guanine-plus-cytosine-rich stretch of DNA located approximately in the middle of the region between GAL1 and GAL10. Analysis of the effects of mutations that alter the region between these two genes, constructed in vitro or selected in vivo, suggest that these guanine-plus-cytosine-rich sequences are required for the expression of both genes. The region of DNA between GAL1 and GAL10 is sufficient for regulation of expression of these genes: fusion of the region to the yeast HIS3 gene places HIS3 under GAL control.

Base Sequence↗
PubMed1984

Clinical experience with intravenous misonidazole for carcinoma of the esophagus: results in attempting radiosensitization of each fraction of exposure.

By using intravenous misonidazole, a hypoxic cell radiosensitizer, we attempted to test the hypothesis of hypoxia as the basis of the relatively poor results seen with radiation therapy in the treatment of carcinoma of the thoracic esophagus. As the peripheral neuropathy of misonidazole was well recognized, we felt that an adequate dose of misonidazole could be given approximately ten times before peripheral neuropathy would necessitate its discontinuation. Because of a desire to maximize any possible effects of radiosensitization, it was decided to administer misonidazole with each fraction of radiation, attempting to deliver curative radiation therapy with only ten fractions of radiation. We thus devised a scheme of radiation consisting of 400 rad twice a week for 5 weeks, a total of 4000 rad. Originally the attempt was made to utilize preoperative radiation therapy and assess the histologic specimens for efficacy. However, major pulmonary toxicity caused revision of that plan. Twenty six patients were treated with radiotherapy alone without surgery, 12 of the patients being randomized to receive intravenous misonidazole with 10 fractions of 400 rad each. In terms of partial response, complete response, local control, and long-term survival, there was no suggestion of any benefit of intravenous misonidazole in these patients. As a consequence, although the number of study patients was small, the investigation was discontinued. Possible explanations for the failure to demonstrate any benefit of misonidazole are discussed.

Combined Modality Therapy↗
PubMed1983

Chloralanyl and propargylglycyl dipeptides. Suicide substrate containing antibacterials.

A set of dipeptides containing the amino acid residues beta-chloroalanine and propargylglycine, which are mechanism-based inactivators of purified microbial enzymes (alanine racemase and cystathionine gamma-synthase, respectively), have been synthesized, and their antibacterial properties in vitro have been evaluated. Dipeptides containing a single beta-chloro-L-alanyl residue (e.g., 3, 5, 9, and 10) or a single L-propargylglycyl residue (e.g., 12 and 15) are potent antibacterials. The in vitro antibiotic activity of beta-chloro-L-alanine and of L-propargylglycine is increased as much as 4000-fold by incorporation of these residues into a dipeptide. Compounds that contain only a single enzyme-inactivating amino acid together with a second L-alanyl residue (3, 5, 12, and 15) have a restricted range of activity: of the species tested, only Streptococcus agalactiae, Staphylococcus aureus, and Staphylococcus epidermidis are sensitive. However, peptides that contain two suicide-substrate residues [e.g., beta-Cl-LAla-beta-Cl-LAla (8) or LppGly-LppGly (18)] are broad-spectrum antibacterials; as many as 12 different species of the 16 surveyed are sensitive. Dipeptides that contain an amino-terminal L-methionyl (9) or an L-norvalyl (10) residue and a carboxy-terminal beta-chloro-L-alanyl unit are also effective against a large number of organisms; the spectra of activity are like those seen for 8 and 18. A "mixed" dipeptide [beta-Cl-LAla-LppGly, (21)] gives apparent synergism of antibiotic action of beta-chloro-L-alanine and of L-propargylglycine when these two residues are incorporated into a single structure. Peptides of the D,D configuration (4, 6, 13, 16, and 20) and ones of L,D stereochemistry (e.g., 7) are not antibacterials. Peptides containing one (11 and 14) and two (17) D,L-propargylglycyl residues are unresolved sets of diastereomers; the mixtures of compounds are between two- and fourfold less active than the correspondingly resolved L,L dipeptides (12, 15, and 18). These findings are consistent with a mechanism of action for these antibiotics involving stereoselective processing of the peptidyl unit in vivo.

Alanine↗
PubMed1983

Is there a trade-off between income and health? The case of hypertensive steelworkers in Canada.

It is often assumed that medical treatment creates a trade-off between good health and income; that is, an individual "pays" for good health by an income loss (at least at the early stages of treatment) compared, for example, with the no-treatment choice. We examined empirical data on hypertensive steelworkers in Canada to evaluate whether such a trade-off exists. We found none. Indeed, those who participated in a treatment program to reduce their blood pressure not only gained improved health but also made small income "gains." Our findings thus challenge the validity of the trade-off assumption and call for further studies of its generalizability.

Adult↗
PubMed1982

A new "cool" lens capsulotomy laser.

A new infrared "cool" laser has been developed to facilitate extracapsular cataract extraction. It has been used to produce clinically and histologically safe, effective anterior and posterior capsulotomies in animal studies. This newly developed ophthalmic laser system operates at a wavelength of 1220 nm, and has a maximal retinal absorption of only 0.1%. This is 100 times less than the retinal absorption at the wavelength of the neodymium-YAG laser. Retinal safety is not dependent on the creation of a plasma shield or on mechanical safety devices, as it is for the neodymium-YAG laser. The 1220 nm wavelength also enhances the "cool laser" effect, so that only 1/100 of the power intensity of the modelocked neodymium-YAG laser is required. In addition to lowering the required ocular exposure this may reduce the likelihood of intraocular damage. To our knowledge this represents the first intraocular use of a laser at this wavelength region (1200 to 1290 nm). A second generation laser, using erbium yttrium lithium fluoride (YLF) as its lasing medium, is currently being developed.

Animals↗
PubMed1982

A placebo-controlled study to determine the efficacy of oral disopyramide phosphate for the prophylaxis of ventricular dysrhythmias after acute myocardial infarction.

1 To evaluate oral disopyramide phosphate in the prophylaxis of dysrhythmias occurring in acute myocardial infarction (MI) patients (presenting within 12 h of symptoms, age 21-70 years), a placebo-controlled, randomized double-blind, in hospital trial was conducted. After prognostic stratification (anterior and non-anterior MI at each of 4 regional hospitals) patients were randomly assigned to receive oral disopyramide phosphate (loading dose 150, 200, or 300 mg followed 6 h later by 100, 150, or 200 mg every 6 h for patients assessed to weigh less than 55, 55-85, or greater than 85 kg, respectively or matching placebo. The primary exclusion criteria were overt heart failure, systolic BP less than 100 mmHg, significant heart block or history of urinary retention. Active drug or placebo was continued for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 for 7 days or until (a) detection of "warning arrhythmias' requiring i.v. lignocaine intervention (greater than 5 premature ventricular contractions (PVCs)/min, R on T PVCs, multifocal PVCs, bigeminal PVCs, ventricular tachycardia or ventricular fibrillation) or (b) onset of exclusion criteria. In addition, plasma drug concentrations were determined and 24 h electrocardiographic tapes were obtained on day 1, and on one of days 4-7 but these results are not presented here. 2 Out of 121 patients entering the trial, 101 had confirmatory ECG and enzyme changes. Of these, 9 of 47 patients receiving disopyramide phosphate required lignocaine compared to 20 of 54 receiving placebo (19% v 37%; P = 0.047). Corresponding numbers for patients discontinuing trial medication for other non-fatal complications of MI were 5 and 3, and for those dying, were 3 (2 infarct extensions and 1 massive infarction), and 0, respectively. Respective numbers discontinuing trial medication for possible drug side effects (viz. urinary retention requiring catheterization) were 6 and 1 (P = 0.031). 3 In circumstances where i.v. therapy is deemed impractical, use of oral disopyramide phosphate given prophylactically in patients with acute MI may reduce the incidence of "warning arrhythmias' by a clinically significant extent.

Adult↗
PubMed1982

Recognition of patients' worries by nurses and by other patients.

Previous studies indicate that patients' worries may not be communicated very effectively to hospital staff. The current study examines whether other patients know more about surgical patients' worries than the nursing staff on the ward. For each patient, the patient, a nurse and a colleague-patient completed a checklist to describe the patients' worries. The results showed that the other patients were more accurate than the nurses both in terms of overall accuracy and, more tentatively, using signal detection theory estimates of sensitivity. As in a previous study, the nurses overestimated the number of worries; the overestimation did not appear to be related to the content of the items nor was it due to patients' underreporting of problems. Relationships between patients, both on the surgical ward and in self-help groups, are discussed.

Adaptation, Psychological↗
PubMed1982

Steps toward resolving cultural conflict in a pediatric hospital.

A serious and potentially life-threatening disease in a young child was identified and resolved through medical intervention. However, in the course of hospitalization, a conflict arose between the mother and the health care providers that required legal constraints on the mother. A retrospective account of this conflict between Western health care providers and a family from a Caribbean culture lends itself to an examination of the role of cultural considerations in pediatric hospital care. Suggestions for resolving cultural conflict in clinical practice are discussed.

Belize↗
PubMed1981

Mechanistic studies on the pyridoxal phosphate enzyme 1-aminocyclopropane-1-carboxylate deaminase from Pseudomonas sp.

The enzyme 1-aminocyclopropane-1-carboxylate deaminase (ACPC deaminase) from a pseudomonad is a pyridoxal phosphate (PLP) linked catalyst which fragments the cyclopropane substrate to alpha-ketobutyrate and ammonia [Honma, M., & Shimomura, T. (1978) Agric. Biol. Chem. 42, 1825]. Enzymatic incubations in D2O yield alpha-ketobutyrate with one deuterium at the C-4 methyl group and one deuterium at one of the C-3 prochiral methylene hydrogens. Stereochemical analysis of the location of the C-3 deuteron was accomplished by in situ enzymatic reduction to (2S)-2-hydroxybutyrate with L-lactate dehydrogenase and conversion to the phenacyl ester. The C-3 hydrogens of the (2S)-2-hydroxybutyryl moiety are fully resolved in a 250-MHz NMR spectrum. Absolute assignment of 3S and 3R loci was obtained with phenacyl (2S,3S)-2-hydroxy[3-2H]butyrate generated enzymatically by D-serine dehydratase action on D-threonine. ACPC deaminase shows a stereoselective outcome with a 3R:3S deuterated product ratio of 72:28. 2-Vinyl-ACPC is also a fragmentation substrate with exclusive regiospecific cleavage to yield the straight-chain keto acid product 2-keto-5-hexenoate. The D isomer of vinylglycine is processed to alpha-ketobutyrate and ammonia at 8% the Vmax of ACPC, while L-vinylglycine is not a substrate. It is likely that ACPC and D-vinylglycine yield a common intermediate--the vinylglycine-PLP-p-quinoid adduct--which is then protonated sequentially at C-4 and then C-3 to account for the observed deuterium incorporation. The D isomers of beta-substituted alanines (fluoroalanine, chloroalanine, and O-acetyl-D-serine) partition between catalytic elimination and enzyme inactivation. Each shows a different partition ratio, arguing against the common aminoacrylyl-PLP as the inactivating species.

Butyrates↗
PubMed1981

Mechanistic studies on reactions of bacterial methionine gamma-lyase with olefinic amino acids.

Methionine gamma-lyase (EC 4.4.1.11), which catalyzes the formation of methanethiol, alpha-ketobutyrate, and ammonia from L-methionine (eq 1), promotes the oxidative deamination of several four- and five-carbon olefinic amino acids (1-5). With the exception of vinylglycine (1), the Vmax rates of keto acid formation from the unsaturated substrate analogues are substantially lower than that for processing of methionine to alpha-ketobutyrate; vinylglycine is deaminated to ketobutyrate and ammonia with a Vmax twice that for L-methionine turnover. L-Allylglycine, L-2-amino-3-trans-pentenoate, and L-2-amino-3-cis-pentenoate (2, 4, 5) are all converted to 2-keto-pentanoic acid (alpha-ketovalerate). L-2-Amino-3-cis-pentenoate (5) is also a time-dependent, irreversible inactivator of the enzyme. None of the other substrate analogues tested appears to inactivate the enzyme. Spectral analysis of the enzymatic reaction with cis isomer 5 reveals the formation of a high-wavelength chromophore (lambda max = 550 nm ) which implies that a beta, gamma-unsaturated pyridoxal p-quinoid (VI) accumulates. No such absorbing species appears to form during the reaction of trans isomer 4 with methionine gamma-lyase. But a 550-nm chromophore develops when both 4 and 5 are reacted with Al(NO3)3 and pyridoxal methochloride in methanolic KOH. It would appear that the geometry of the protein and the olefinic amino acid as an intermediate enzyme-substrate adduct controls the kinetics of reaction, such that azaallylic isomerization becomes selectively rate determining for reaction with 5. When this isomerization is slow, an accumulating Michael-type acceptor (VI) could lead to the observed irreversible inactivation of the enzyme.

Alkenes↗
PubMed1981

Effect of maternal cigarette smoking on Apgar scores.

As shown in a total of 43,492 live-born singleton infants, the proportion of low and depressed Apgar scores is related to the extent of maternal cigarette usage during pregnancy. In particular, the three-pack level of smoking (41 to 60 cigarettes per day) is reflected in a near-quadrupling of low and depressed one-minute and five-minute Apgar scores in both blacks and whites and also after exclusion of prematurely born infants.

Apgar Score↗
PubMed1981

The pharmacodynamics of bucainide (RHC G233): pharmacokinetic parameters and relationship between plasma levels and the effect on the electrocardiogram in the dog.

The pharmacodynamic profile of bucainide dimaleate (RHC G-233) in dogs has been studied. The first observed pharmacologic effect was a change in the ECG pattern (T-wave duration and amplitude) that occurred after an average intravenous dose of 2.7 mg/kg. The average plasma concentration of bucainide was approximately 350 ng/ml. Analysis of data from dogs that received a dual infusion of bucainide indicated that bucainide has an extensive volume of distribution, with an average value of approximately 26 l/kg. An average terminal half-life of 89 minutes was observed. Studies with the radiolabeled drug in rats and dogs also demonstrated the drug's large volume of distribution, and its initial rapid disappearance from the blood. Tissue distribution studies in the rat after administration of the radiolabeled drug showed that bucainide is rapidly taken up by the tissues.

Animals↗
PubMed1980

Anxiety in surgical patients.

The natural course of anxiety before and after surgery was examined using the State-Trait Anxiety Inventory in 4 studies involving 136 surgical patients. The results suggested that high levels of anxiety were experienced before admission to hospital, between admission and surgery and following surgery, and were not restricted to the immediate pre-operative period. Only a small percentage of patients reached their maximum level of anxiety on the morning of surgery. These results have implications for those planning interventions to alleviate anxiety associated with surgery and for those studying surgical stress as a model for other naturally occurring stresses.

Adolescent↗