Search PubMed⌕ Search

Biomedical subjects

D Robertson

Publications and source records attributed to D Robertson.

At least 379 records · Page 21Linked to original sources
PubMed1985

Bretylium: relations between plasma concentrations and pharmacologic actions in high-frequency ventricular arrhythmias.

Although it is widely assumed that the early arrhythmogenic and pressor responses to bretylium are caused by catecholamine release from the adrenergic neuron, this assumption has not been systematically studied in humans. Pharmacologic responses to a placebo infusion and 3 separate bretylium infusions (2.5, 5.0, 10 mg/kg over 60 minutes) were assessed in 6 patients with recurrent, nonsustained ventricular tachycardia. Plasma bretylium concentration, blood pressure (BP), plasma norepinephrine (NE) concentration, arrhythmia frequency and adrenergic neuronal blockade (assessed by the presence or absence of reflex venoconstriction) were measured. Adrenergic blockade was seen with every bretylium infusion and at a time when relatively small amounts of bretylium had been administered (range 160 to 750 mg, median 252). Temporal relations (p less than 0.03) were noted among the time of onset of adrenergic neuronal blockade, onset of the pressor response, increase in NE plasma concentration and increase in ventricular arrhythmia frequency. BP responses during the infusions were linearly related to change in plasma NE at the time of development of adrenergic neuronal blockade. Bretylium plasma concentrations higher than 3 micrograms/ml were frequently associated with a short-lived pressor response. There was a significant relation (p less than 0.06) between the increase in plasma NE during the infusion and an increase in ventricular arrhythmia frequency. Reduction in arrhythmia frequency was seen in only 1 patient, beginning 6 hours after the development of adrenergic neuronal blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

A cytohistological analysis of roots whose growth is affected by a 60-Hz electric field.

Roots of Pisum sativum were exposed for 48 h to 60-Hz electric fields of 430 V/m in an aqueous inorganic growth medium. The growth in length of the exposed roots was 44% of that for control roots. Root tips were analyzed for mitotic index and cell cycle duration. Mature, differentiated root sections from tissue produced after electrode energization were analyzed for cell lengths and number of files. The major reason for the observation that exposed roots are shorter than control roots is that cell elongation in the former is greatly diminished relative to controls.

Cell Cycle↗
PubMed1985

Determination of hydrazine in pharmaceuticals IV: Hydrazine and benzylhydrazine in isocarboxazid.

A GC procedure for the simultaneous determination of hydrazine and benzylhydrazine in isocarboxazid raw material and tablet formulations has been developed. The method is based on the reaction of benzoyltrifluoroacetone with hydrazine and benzylhydrazine to form the corresponding pyrazole derivatives. The minimum detectable amounts of hydrazine and benzylhydrazine in isocarboxazid are 0.002 and 0.02%, respectively.

Chromatography, Gas↗
PubMed1985

Effects of indomethacin on systemic and coronary hemodynamics in patients with coronary artery disease.

The effects and possible mechanisms of actions of indomethacin on systemic and coronary hemodynamics were studied in 17 patients with coronary artery disease. Group I patients (12) were given either indomethacin or placebo in the absence of prior cyclooxygenase inhibition and group II (five) were given indomethacin after prior treatment with 2600 mg of aspirin. In group I, systolic blood pressure rose from a baseline of 136 +/- 5 mm Hg to a peak level of 158 +/- 8 mm Hg 5 minutes after drug (p less than 0.01). This was associated with a fall in coronary blood flow and a rise in coronary vascular resistance from a baseline of 1.36 +/- 0.4 mm Hg/ml/min to 1.99 +/- 0.7 mm Hg/ml/min 5 minutes after indomethacin (p less than 0.01). Immunoreactive thromboxane B2 levels fell from 191 to 1.4 ng/ml. No changes were noted in plasma renin activity, angiotensin II, or catecholamine levels. Immunoreactive thromboxane B2 levels were undetectable throughout the study period in group II patients and the blood pressure response to indomethacin was attenuated. Baseline coronary blood flow was significantly higher (p less than 0.01) and baseline coronary vascular resistance significantly lower (p less than 0.01) than in group I. At all time points after indomethacin, the fall in coronary blood flow was greater and the increase in coronary vascular resistance less in group II versus group I (p less than 0.001). These findings suggest a dissociation between the effect of indomethacin on systemic and coronary hemodynamics, the former apparently being more prostaglandin-dependent than the latter.

Adult↗
PubMed1985

Prevention of metabolic alkalosis induced by gastric fluid loss using H2 receptor antagonist.

Gastric fluid loss is a common cause of metabolic alkalosis. We studied various acid-base parameters in 20 patients undergoing continuous nasogastric (NG) suctioning for periods ranging from 3 to 17 days. Ten patients received cimetidine 300 mg intravenously every 6 hr (cimetidine-treated group). The remaining 10 patients received an antacid compound through the NG tube (control group). The rise in plasma bicarbonate concentration was significantly greater in the control group as compared to the cimetidine-treated group. As expected, gastric acid output was considerably lower in the cimetidine-treated group than in the control group. We conclude that cimetidine administration may be used in preventing metabolic alkalosis associated with gastric fluid loss by inhibiting gastric secretion of HCl.

Adolescent↗
PubMed1985

Kainic acid selectively alters auditory dendrites connected with cochlear inner hair cells.

Cochleas of adult guinea pigs and rats, and 6-day-old rat pups, were injected, through the round window, with 2 microliters of artificial classical Konishi perilymph containing 1 nmol kainic acid (KA). 5 min later, they were fixed, removed, and processed for electron microscopy. In all KA-treated cochleas, the injection resulted in a severe swelling of auditory dendrites below the inner hair cells (IHCs). Below the outer hair cells (OHCs), the swelling appeared only in the 6-day-old rats, not in adult animals. These results are significant in three different ways: (1) They confirm the strong difference between afferents innervating the IHCs and the OHCs in adult cochleas. (2) They shed some light on the synaptic plasticity found at the OHC level during synaptogenesis. (3) They support the hypothesis that glutamate, or a related substance, is the IHC neurotransmitter.

Age Factors↗
PubMed1985

Physiological and morphological characterization of efferent neurones in the guinea pig cochlea.

Efferent neurones within the intraganglionic spiral bundle of the guinea pig cochlea were characterized in terms of their response properties, and their pattern of termination within the receptor organ revealed by intracellular labelling with horseradish peroxidase. All neurones subsequently identified as efferent neurones had clear features of their response properties which distinguished them from primary auditory afferents. They had long latency, low maximum discharge rate and low levels of spontaneous activity under Nembutal/Innovar anaesthesia. The pattern of discharge was extremely regular, revealed by symmetrical interspike interval histograms. 49.4% responded best to ipsilateral, 43.3% to contralateral sound and a third group of 7.3% responded equally well to either ipsilateral or contralateral sound. In cochleae in good physiological condition, these efferents were as sensitive and as sharply tuned as primary afferents with the same characteristic frequencies (CFs). All efferents fully traced in histological processing terminated on the outer hair cells. Several efferents showed extensive branching beneath the inner hair cells which might represent en passant synapses with other neuronal elements. There was clear evidence of tonotopic organization of the efferent projection. The site of termination on the outer hair cells in most instances was very close to the region of the cochlea predicted from the fibres' CF and the known place-frequency map for primary afferent neurones in the guinea pig.

Anesthesia, General↗
PubMed1985

Brainstem location of efferent neurones projecting to the guinea pig cochlea.

Retrograde transport of horseradish peroxidase using tetramethylbenzidine as a chromagen was used to map the cell bodies of origin of the efferent projection to the cochlea in the guinea pig. Large numbers of small labelled neurones were found within the body of the lateral superior olivary nucleus (LSO) ipsi-lateral to the injected cochlea. Labelled cells within the contra-lateral LSO were extremely rare (1% or less). Large labelled neurones were found both ipsi-laterally and contra-laterally in the dorsomedial periolivary region, including the medial nucleus of trapezoid body and in the ventral and lateral nuclei of the trapezoid body and the ventral nucleus of lateral lemniscus. It was concluded that some aspects of the distribution of these efferent neurones in the guinea pig are similar to the situation in the rat, whilst others resemble more closely the arrangement found in cat.

Animals↗
PubMed1985

Very rapid adaptation in the guinea pig auditory nerve.

Guinea pig auditory ganglion cell responses to 100-ms duration tone bursts were recorded over a range of stimulus intensities. The responses, recorded in the form of peristimulus/poststimulus time histograms, were analysed by reduction into two phases. The first phase was a rapid exponential adaptation from an initial onset response; the second was a more gradual reduction in the firing rate which, over the 100 ms duration of the stimulus, appeared to be a linear function of time. The first, rapid, phase was nonlinear in its response to changes in stimulus intensity, exhibiting a change in amplitude and having a time constant which decreased with increasing intensity. Individual units were consistent in the magnitude and time course of this phase. The second phase was also nonlinear with intensity, and was far more variable from unit to unit. With the recording parameters employed it was not possible to determine whether the effect of intensity on the second phase was an effect on the magnitude or time course, or both. Stimulus termination responses were also analysed, and typically were of one of two forms. If, at any particular stimulus intensity, the unit under study showed little sign of the slower adaptation then the termination response was a simple depression of activity (perhaps to zero) which recovered with an exponential time constant of about 25 ms, independent of intensity. If, however, the peristimulus responses showed a significant amount of the slow adaptation then the termination responses also exhibited a second, slower, phase of recovery. This was modelled over the recording epoch as a linear function of time. The magnitude of the slow offset response also increased with intensity faster than did the average firing rate.

Acoustic Stimulation↗
PubMed1985

Reflexes unique to myocardial ischemia and infarction.

Although arrhythmias caused by myocardial ischemia are a well recognized cause of sudden death, the potential influence of cardiogenic reflexes originating in areas of ischemia has received less attention. In this study, 12 patients with well documented single vessel coronary artery spasm, with a total of 2,240 episodes of transient transmural ischemia, are described. Continuous electrocardiographic and hemodynamic recordings were analyzed to determine possible relations between the anatomic area of ischemia and patterns of change in blood pressure and heart rate. Of seven patients with ischemia of the posterior or inferior left ventricular wall, six had associated bradycardia and hypotension, an apparent Bezold-Jarisch response. Only one of five patients with anterior ischemia had a similar response. A hypertensive, tachycardiac response resembling the James reflex was seen in two of the patients with anterior ischemia, with an increase in blood pressure of 36/22 +/- 12/6 mm Hg and an increase in heart rate of 8 +/- 3 beats/min. This increase began before the onset of chest pain and was seen even in asymptomatic episodes. These reflexly mediated hemodynamic responses may modulate the direct effects of myocardial ischemia and could play a role in sudden cardiac death.

Angina Pectoris↗
PubMed1985

The QRS complex during transient myocardial ischemia: studies in patients with variant angina pectoris and in a canine preparation.

We made continuous electrocardiographic recordings on magnetic tape during 15 episodes of ischemia in five patients with variant angina to determine the characteristics of the QRS changes. Orthogonal leads were used and the electrocardiograms were analyzed visually and by digital computer. Changes were quantified by subtracting baseline electrocardiograms from those obtained during ischemia. Large changes in the QRS occurred during ischemia but the waveform quickly returned to baseline when the episode subsided. In all patients there was prolongation of the QRS duration and an increase in QRS voltage during the terminal 40 msec of the waveform in the lead(s) showing the most marked ST displacement. The increase in the terminal QRS could be represented by a vector directed toward the ischemic zone. In a given patient the amplitude of ST displacement varied between episodes, presumably because of variation in the intensity of ischemia, but the QRS changes were directionally similar in each episode. In two patients there was also a smaller change involving the initial 40 msec of the QRS that could be represented by a vector directed away from the ischemic zone. To determine the possible mechanism for the electrocardiographic changes, ischemic episodes of 120 to 150 sec were produced in seven dogs and electrocardiographic recording and analysis techniques similar to those used in patients were employed. Myocardial conduction velocity was measured in three directions in the ischemic zone and was correlated with simultaneous electrocardiographic recordings from the body surface. The electrocardiographic changes in the dog preparation were virtually identical to those in the patients and strongly correlated with a fall in myocardial conduction velocity. We conclude that the QRS changes during variant angina result from the altered excitation pattern produced by conduction delay in the ischemic zone. The probable cause for the increase in terminal QRS voltage is delayed (and uncancelled) activation of the ischemic zone.

Angina Pectoris, Variant↗
PubMed1985

Prostacyclin biosynthesis and platelet function in autonomic dysfunction.

We measured urinary excretion of the principal metabolite of prostacyclin, PGI-M (2,3-dinor-6-keto-PGF1 alpha) in two patients with Shy-Drager syndrome and three with idiopathic orthostatic hypotension. All patients had a rise in blood pressure (30 +/- 6 mm Hg) after ingestion of 50 mg indomethacin. Urinary excretion of PGI-M was normal and fell 57 +/- 11% after administration of indomethacin. In two subjects, there was no evidence of any circulating inhibitor of platelet aggregation when hypotension was induced by upright posture or ingestion of a meal. Despite the efficacy of indomethacin, these patients with autonomic dysfunction did not show increased production of the vasodilator prostanoid prostacyclin.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Induced type-B reticulum cell neoplasia of CBA mice. I. Phenotypic similarities between tumorigenic reticulum cells and normal accessory cells.

The phenotype and tumorigenicity of various cell types which occur in induced, transplantable type-B reticulum cell neoplasms of CBA strain mice have been examined. Evidence is presented that the neoplasms contain tumorigenic cells, morphologically defined as reticulum cells, having several phenotypic characteristics of the lymphoid dendritic and veiled accessory cells of normality, and macrophages and small lymphoid cells which are probably reactive cells of host origin.

Animals↗
PubMed1985

Zinc levels of hospitalized elderly.

Zinc status was evaluated in 99 consecutive elderly patients admitted to a geriatric assessment unit. The assessment of zinc status was based on measurement of plasma, erythrocyte, and urinary zinc levels by atomic absorption spectrophotometry; serum lactic dehydrogenase and alkaline phosphatase by standard laboratory methods; and dietary intake by the food frequency questionnaire method. Mean (+/- standard deviation) plasma zinc concentration was 72 +/- 16 micrograms/100 ml (N = 91). Although 67% of the group had plasma zinc levels in the deficient range, only three patients had values below the normal range for erythrocyte zinc and none fell below the reference range for urinary zinc per 24 hours (N = 15) or the urinary zinc:creatinine ratio. Mean values for the other parameters of zinc status were 1.27 +/- 0.26 micrograms/10(9) RBC for erythrocyte zinc, 285 +/- 217 micrograms/24 hours for urinary zinc, and 588 +/- 309 micrograms/gm for the urinary zinc:creatinine ratio. Serum alkaline phosphatase and lactic dehydrogenase were not specific indicators of zinc status. Forty-six percent had adequate and 54% inadequate dietary intakes (N = 46). Twenty percent were receiving an inadequate intake of meat products, suggesting that the majority (80%) were ingesting an adequate supply of zinc-rich foods. Zinc status appeared to be adequate in this population.

Aged↗
PubMed1984

Alterations in leukocyte beta-receptor affinity with aging. A potential explanation for altered beta-adrenergic sensitivity in the elderly.

The elderly have reduced beta-adrenergic sensitivity to agonists, but no change in receptor density. We investigated the relation between beta-receptor affinity for agonists and age in beta-receptors on lymphocytes from 20 healthy men 21 to 74 years old. As an index of beta-receptor affinity for agonists, we determined the IC50 of isoproterenol--the concentration of isoproterenol required to inhibit 50 per cent of iodohydroxybenzylpindolol binding in vitro. We found that receptor affinity for agonists was correlated with age and plasma norepinephrine concentration. Twelve subjects (six 21 to 29 years old and six 55 to 74 years old) were also studied in both the supine and upright positions. In samples obtained in the supine position, the proportion of receptors binding agonist with a high affinity was decreased in the older subjects as compared with the young subjects (22 +/- 1 per cent vs. 38 +/- 3 per cent; P less than 0.05). With upright posture and the associated acute elevation of endogenous plasma catecholamines, the proportion of receptors binding agonist with a high affinity was reduced in the young; no such changes were seen in the older subjects. The data suggest that reduced beta-receptor affinity for agonists may be an explanation for altered beta-adrenergic sensitivity in the elderly.

Adrenergic beta-Agonists↗
PubMed1984

Murine B cell lymphopoiesis in long term culture.

A method is described for establishing continuous cultures of early B lymphocytes from mouse bone marrow. Total bone marrow elements are cultured at 37 degrees C in medium containing 5% fetal calf serum and 10(-5) M 2-mercaptoethanol. Under these conditions, adherent bone marrow cells grow to confluency by 2-3 weeks and provide a feeder layer on which the growth of the B lymphocytes depends. Lymphoid cell growth becomes apparent by 3-5 weeks. Such cultures are a rich source of pre-B cells, B cells and potentially stem cell-like elements capable of immunoglobulin gene rearrangement. The procedures for initiating and maintaining the bone marrow cultures are described in detail as are the phases of growth through which the cultures should progress. Also included are methods for preparing and manipulating low cell-density feeder layers, on which B cell populations can be expanded, and a method for obtaining pre-B and B cell clonal lines. The lymphoid cells which are obtained from these cultures early after establishment (3-8 weeks) are predominantly pre-B cells which can serve as targets for transformation by Abelson murine leukemia virus. Cells obtained from older cultures (3-6 months) frequently are B cells that express both membrane IgM and IgD. The numbers of cells which can be obtained from these mass cultures and clonal lines are sufficient to analyze the molecular processes involved in B cell maturation, virus transformation and antigen activation.

Animals↗