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Biomedical subjects

D Montgomery

Publications and source records attributed to D Montgomery.

At least 73 records · Page 4Linked to original sources
PubMed1990

Plasma-level response relationships with fluoxetine and zimelidine.

The results of pharmacokinetic studies of two recent 5-HT uptake inhibitors, zimelidine and fluoxetine, have pointed to the inadequacy of open-dose rising studies for establishing the most appropriate dose of new antidepressants. High plasma concentrations of the active metabolites, norzimelidine and norfluoxetine, were associated with a poorer therapeutic response in patients suffering from major depression. High drug plasma concentrations are also associated with increased side effects. Large fixed-dose placebo controlled studies with fluoxetine have confirmed the findings of the small pharmacokinetic study that lower doses are more effective. Fixed-dose pharmacokinetic studies are recommended as part of the program to establish the best dose of new antidepressants.

Depressive Disorder↗
PubMed1989

Energetics of diphtheria toxin membrane insertion and translocation: calorimetric characterization of the acid pH induced transition.

The pH and temperature stabilities of diphtheria toxin and its fragments have been studied by high-sensitivity differential scanning calorimetry. These studies demonstrate that the pH-induced conformational transition associated with the mechanism of membrane insertion and translocation of the toxin involves a massive unfolding of the toxin molecule. At physiological temperatures (37 degrees C), this process is centered at pH 4.7 at low ionic strength and at pH 5.4 in the presence of 0.2 M NaCl. At pH 8, the thermal unfolding of the nucleotide-bound toxin is centered at 58.2 degrees C whereas that of the nucleotide-free toxin is centered at 51.8 degrees C, indicating that nucleotide binding (ApUp) stabilizes the native conformation of the toxin. The unfolding profile of the toxin is consistent with two transitions most likely corresponding to the A fragment (Tm = 54.5 degrees C) and the B fragment (Tm = 58.4 degrees C), as inferred from experiments using the isolated A fragment. These two transitions are not independent, judging from the fact that the isolated A fragment unfolds at much lower temperatures (Tm = 44.2 degrees C) and that the B fragment is insoluble in aqueous solutions when separated from the A fragment. Interfragment association contributes an extra -2.6 kcal/mol to the free energy of stabilization of the A fragment. Whereas the unfolding of the entire toxin is irreversible, the unfolding of the A fragment is a reversible process. These findings provide a thermodynamic basis for the refolding of the A fragment after reexposure to neutral pH immediately following translocation across the lysosomal membrane.

Calorimetry, Differential Scanning↗
PubMed1989

Effects of anxiolytic and anxiogenic drugs on exploratory activity in a simple model of anxiety in mice.

Chlordizaepoxide, pentylenetrazole, phenobarbital, N-methyl-beta-carboline-3-carboxamide (FG-7142), buspirone and the novel serotonin3 receptor (5-HT3) antagonist, 3-tropanyl-indole-3-carboxylate (ICS 205-930), were examined in the two-compartment exploratory model (Crawley and Goodwin, 1980). The results indicated that, utilizing the time mice spend in the dark side of the apparatus as an index of anxiety, increased the sensitivity of the model and enabled both anxiolytic and anxiogenic agents to be detected.

Animals↗
PubMed1989

Stair stepping efficiency of mentally handicapped and nonhandicapped adult females.

Net efficiency for stair stepping was compared between 15 mentally handicapped (MH) and 15 nonhandicapped (NH) women of comparable chronological age. Efficiency was computed as the percentage of the energy output divided by the energy expenditure. Energy expenditure was assessed by the performance of subjects on a double stair stepping apparatus, stepping at three work rates (14, 17, and 19 asc/min), repeated on four test days. Open-circuit spirometric techniques were used to measure oxygen uptake. The three-way (Group x Stepping Rates x Days) repeated measures ANOVA indicated that: (1) NH women stepped more efficiently than MH women (p less than 0.01). Mean stepping efficiency was 17.1% for the NH group, and 15.6% for the MH group; (2) MH women did not show improvement in stepping efficiency over the four days, although there was a 20% increase in the number of MH subjects capable of completing the fastest stepping rate over the four days; and (3) MH subjects were more efficient at 17 and 19 asc/min than at 14 asc/min.

Adult↗
PubMed1989

Intermittent 3-day depressions and suicidal behaviour.

Intermittent short-lived episodes of depression were examined in a group of 20 recurrent suicidal attempters without major depression, classified misleadingly as borderline personality disorders on DSM-IIIR, during careful prospective follow-up for between 4 and 6 months. The duration of depressions clustered tightly around a median of 3 days with two thirds lasting between 2 and 4 days. They occurred erratically and unpredictably with a median interval of 18 days and were seen to be moderate to severe measured on the MADRS in 70% of episodes.

Crisis Intervention↗
PubMed1989

Prophylactic treatment of depression: a public health issue.

The majority of depressive illness is a chronic and relapsing, frequently occurring illness, which carries significant social and economic consequences for the sufferer. Depression is also associated with increased morbidity and mortality from physical illness and suicide. Long-term antidepressant treatment is needed for at least 6 months after the resolution of the symptoms of an acute episode to consolidate recovery. In recurrent depression, treatment over a much longer period is required to reduce the risk of a new episode occurring. It is clear from the prophylactic studies, which require careful and appropriate methods, that some half of the recurrent episodes of depression are preventable by adequate prophylactic treatment with antidepressants. This effect has been clearly demonstrated with some of the newly introduced 5-HT uptake inhibitors. The disadvantages of long-term treatment have to be weighed against the risks and costs, personal, social and economic, of the illness.

Antidepressive Agents↗
PubMed1986

Antiarrhythmic vs. antifibrillatory activity of the basic diphenylhydantoin derivative 3-[3-(4-phenyl-1-piperidyl)propyl]-5-(4-methoxyphenyl)-5-phenylhydantoin hydrochloride.

The effects of 3-[3-(4-phenyl-1-piperidyl)propyl]-5-(4-methoxyphenyl)-5-phenylhydantoin hydrochloride (TR 2985), a basic diphenylhydantoin derivative, were studied in four canine models of experimental cardiac dysrhythmias. In conscious dogs, 48 h after myocardial infarction, TR 2985 significantly reduced the frequency of spontaneous ventricular arrhythmias. However, in anesthetized dogs, TR 2985 produced only a slight and insignificant increase in the ventricular fibrillation threshold. In conscious dogs, 4 to 7 days after myocardial infarction, TR 2985 failed to prevent the electrical induction of reentrant ventricular tachycardia, and failed to protect against the development of ventricular fibrillation in response to ischemia at a site distant from the previous infarction. These results indicate that TR 2985 may be effective in preventing arrhythmias of a non-reentrant nature, but may be relatively ineffective in preventing reentrant ventricular tachycardia or ventricular fibrillation.

Anesthesia, General↗
PubMed1985

Postinfarction sudden death: significance of inducible ventricular tachycardia and infarct size in a conscious canine model.

The relationship between inducible ventricular tachycardia in the convalescent phase of myocardial infarction and subsequent spontaneous ventricular fibrillation is uncertain. Thirty conscious instrumented dogs underwent programmed ventricular stimulation 5 days after anterior infarction; 15 had inducible ventricular tachycardia and 15 were noninducible. Following programmed ventricular stimulation, the application of a 150 uA current to the intima of the proximal circumflex artery initiated intimal damage, thrombosis, and acute ischemia of the posterolateral wall. After 20 minutes of ischemia, 73% inducible and 15% noninducible animals developed ventricular fibrillation (p less than 0.005) without previous hypotension. At 24 hours, 7% inducible and 85% noninducible animals survived (p less than 0.001). Anterior infarct size (percentage of left ventricular mass) was much larger in inducible (24.7 +/- 1.7%) than in noninducible (5.3 +/- 1.1%) (p less than 0.001) animals. Inducible ventricular tachycardia following infarction was highly predictive of spontaneous ventricular fibrillation during a later ischemic episode in this model. The mass of previously injured myocardium was a critical determinant of both.

Animals↗
PubMed1983

Viscous, resistive magnetohydrodynamic stability computed by spectral techniques.

Expansions in Chebyshev polynomials are used to study the linear stability of one-dimensional magnetohydrodynamic quasiequilibria, in the presence of finite resistivity and viscosity. The method is modeled on the one used by Orszag in accurate computation of solutions of the Orr-Sommerfeld equation. Two Reynolds-like numbers involving Alfvén speeds, length scales, kinematic viscosity, and magnetic diffusivity govern the stability boundaries, which are determined by the geometric mean of the two Reynolds-like numbers. Marginal stability curves, growth rates versus Reynolds-like numbers, and growth rates versus parallel wave numbers are exhibited. A numerical result that appears general is that instability has been found to be associated with inflection points in the current profile, though no general analytical proof has emerged. It is possible that nonlinear subcritical three-dimensional instabilities may exist, similar to those in Poiseuille and Couette flow.

Journal Article↗
PubMed1983

Malignant melanoma of the iris after 30 years.

We report a case of a spindle cell malignant melanoma of the iris that was excised locally in 1952, only to become clinically evident again 25 years later. The tumor exhibited unusually slow, compact growth, with local infiltration into the ciliary body and dispersion of tumor cells into the angle structures and onto the posterior cornea. No extraocular dissemination was evident. Histologically, the cells in the specimens taken in 1952, 1978, and 1981 had remarkably similar morphological findings. The patient has had no recurrences 12 months after enucleation.

Aged↗