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Biomedical subjects

J M Harrison

Publications and source records attributed to J M Harrison.

At least 73 records · Page 4Linked to original sources

Drug resistance in Mycobacterium tuberculosis: a survey over 25 years in Blackburn.

Over the past 25 years the incidence of tuberculosis in Blackburn has changed from one that was below the national average to one which is consistently in the 10 highest local authority areas in England and Wales. A survey of primary and acquired drug resistance over the same period included 974 ethnic white patients and 538 of Indian subcontinent ethnic origin. Primary drug resistance in the white population has fallen consistently from 1965 onwards and is now zero. Only one case of acquired resistance has occurred in the last five years. Primary resistance in the immigrant community has been 11-15% from 1965 onwards, and five cases of acquired resistance have occurred since 1970. The pattern of drug resistance over this period supports the view that there is no evidence of cross infection between the native white and immigrant ethnic groups.

Antitubercular Agents↗

Rod-cone interactions in the ERG of a patient with Bardet-Biedl syndrome.

During routine ERG testing of a patient with Bardet-Biedl syndrome, we encountered an ERG anomaly not previously reported. A white flash which produced a response during light adaptation would produce no ERG when the retina was dark-adapted. Possible explanations for this phenomenon are discussed.

Adult↗

Voluntary alteration of pattern visual evoked responses.

Pattern and flash visual evoked responses (VERs) were recorded from a large group of ophthalmologically normal subjects during two conditions: in one they were instructed to attend to the stimulus and in the other they were instructed to ignore the stimulus but maintain their gaze on the stimulus. Pattern VERs were recorded from 42 subjects. Fixation was constantly monitored during both attend and ignore conditions and no changes of fixation were noted at any time. The amplitude of the major positive wave of the pattern VERs produced by both 50- and 25-min checks was reduced significantly during the ignore condition. The implicit time of this positive wave did not differ significantly during the two conditions. The pattern VERs of eight subjects were extinguished and the VERs of another three subjects were unrecognizable during the ignore condition. Flash VERs produced by 10 flashes per second were recorded from 38 of the 42 subjects. There were no significant differences between the amplitudes recorded during the attend and ignore conditions.

Adult↗

Control of responding by the location of sound: role of binaural cues.

In auditory localization experiments, where the subject observes from a fixed position, both relative sound intensity and arrival time at the two ears determine the extent of localization performance. The present experiment investigated the role of binaural cues in a different context, the sound-position discrimination task, where the subject is free to move and interact with the sound source. The role of binaural cues was investigated in rats by producing an interaural imbalance through unilateral removal of the middle auditory ossicle (incus) prior to discrimination training. Discrete trial go-right/go-left sound-position discrimination of unilaterally incudectomised rats was then compared with that of normal rats and of rats with the incus of both sides removed. While bilateral incus removal affected binaural intensity and arrival times, the symmetry of sound input between the two ears was preserved. Percentage of correct responses and videotaped observations of sound approach and exploration showed that the unilateral rats failed to localize the sounding speaker. Rats with symmetrical binaural input (normal and bilaterally incudectomised rats) accurately discriminated sound position for the duration of the experiment. Previously reported monaural localization based upon following the intensity gradient to the sound source was not observed in the unilaterally incudectomised rats of the present experiment. It is concluded that sound-position discrimination depends upon the use of binaural cues.

Animals↗

Reduction of blood loss in knee arthroplasty.

The purpose of this study was to investigate ways of reducing and controlling blood loss and postoperative anaemia in total condylar knee arthroplasty performed under tourniquet. The study covers a two year period to December 1982. Reduction of blood loss was successfully achieved by being aware of the very rich blood supply to the knee and utilizing diathermy for potential bleeders before and after the release of the tourniquet and employing various haemostatic measures. All these patients need blood transfusion, as well as the measures to reduce blood loss, so that they do not become anaemic postoperatively.

Aged↗

The functional analysis of auditory discrimination.

Mammals have evolved the ability to acquire auditory discriminations. The characteristics of this discriminative ability presumably fit the natural conditions under which discriminations are normally acquired. The purpose of this paper is to review experiments which were directed at showing that auditory discriminations are most rapidly acquired when natural features are incorporated into the experiments. The experiments were also directed at discovering the underlying characteristics of the discriminative ability. When animals were trained to discriminate the position of a sound source in which natural features were incorporated into the experiment, the discrimination was acquired in one trial. Manipulation of the natural features suggested that one trial acquisition depends upon the following. (1) Stimulus novelty; the effect of reinforcement is stronger in the presence of novel than familiar stimuli. (2) Specific behavioral effect of reinforcement; the effect of reinforcing a response in the presence of a novel auditory stimulus is to increase the strength of approaching and manipulating the sound source.

Animals↗

Effects of age on some behavioral characteristics of novel auditory stimuli in the rat.

Low intensity novel auditory stimuli have two behavioral characteristics. First, such stimuli elicit exploratory behavior directed at the sound source. Second, novel stimuli gain control of responding in a discriminative task more rapidly than familiar stimuli. Experiments were carried out to investigate these two characteristics of novel stimuli. In the first experiment 3, 12 and 30 month old rats were given three sessions, 24 hours apart, of exposure to an initially novel low intensity series of noise pulses; the number of exploratory responses of the sounding speaker per session was counted. In the second experiment, 12 and 30 month old rats were trained in a sound location discrimination in which the stimuli were made familiar prior to discrimination training. Age had no effect on the amount, habituation and retention of habituation of exploration of the sounding speaker. In the second experiment, the 12 month and 30 month old animals acquired the discrimination at the same rate; again no age effect was found.

Aging↗

The fate of dibenz[b,f]-1,4-oxazepine (CR) in the rat, rhesus monkey and guinea-pig. Part I. Metabolism in vivo.

The fate of dibenz[b,f]-1,4-[11(14)-C]oxazepine (CR) in rats, rhesus monkey and guinea-pig and in isolated perfused rat livers has been examined. 14C-CR was administered to rats at doses from 1.56 to 3470 mumol/kg and irrespective of dose or route of administration most (59-93%) was eliminated in the urine as primarily the sulphates of the 7-, 4- and 9-hydroxylated 10,11-dihydrodibenz[b,f]-1,4-oxazepine-11(10H)-one. In blood, both in vivo and in liver perfusates, CR concentrations decreased biphasically to be replaced initially with CR-lactam (dihydrodibenz[b,f]-1,4-oxazepine-11(10H)-one), followed by the sulphates of the 7-, 4- and 9-hydroxylactams. The rate of disappearance of CR in liver perfusates was slower than in vivo. Bile contained only small amounts of sulphate conjugates and significant amounts of conjugated 2-amino-2'-hydroxymethyldiphenyl ether (amino alcohol). This was not identified in the urine or blood of rats. Preliminary studies in rhesus monkey and the guinea-pig show similar excretory patterns and metabolites. However, only free hydroxylactams were isolated from monkey urine and traces of the amino alcohol were detected in guinea-pig urine. Whole-body autoradiography of mice confirm the rapid disappearance of CR from blood into heart, liver, kidneys and small intestine with evidence of biliary excretion. It is consistent with the rat studies showing the rapid absorption of a highly lipophilic compound undergoing hepatic metabolism, biliary secretion, enterohepatic recirculation and renal excretion.

Animals↗

The fate of dibenz[b,f]-1,4-oxazepine (CR) in the rat. Part II. Metabolism in vitro.

CR (dibenz[b,f]-1,4-oxazepine) is metabolized by rat liver 105 000 g supernatant fractions by (a) ring opening and reduction to 2-amino-2'-hydroxymethyldiphenyl ether and (b) oxidation at C11 to give a cyclic lactam. Reaction (a) is NADPH-dependent, decreased by dialysis and methylene blue, whereas reaction (b) is heat-resistant, inactivated by dialysis, inhibited by CN-, p-chloromercuribenzoate, amytal and menadione, and stimulated by methylene blue, phenazine methosulphate and 2,6-dichlorophenol indophenol. Reaction (a) is similar to that of aldehyde reductases (E.C.1.1.1.2) and reaction (b) to that of molybdenum hydroxylases (E.C.1.2.3.1). Reaction (a) is also catalysed by an NADH-dependent enzyme in liver microsomes and subsequent hydroxylation of the lactam also occurs in this cell fraction. Some extrahepatic metabolism of CR occurs via the same routes in kidney, small intestine and lung, though the yield is limited. Digestive gland extract of Helix pomatia converts CR to its lactam in significant amounts. The metabolism of CR in vitro is similar to that predicted from observations in vivo.

Animals↗

The fate of dibenz[b,f]-1,4-oxazepine (CR) in the rat. Part III. The intermediary metabolites.

The fates of several intermediates of dibenz[b,f]-1,4-oxazepine (CR) metabolism in vivo and in vitro in rats have been examined to establish the metabolism and excretory sequence of CR. The ring-opened 2-amino 2'-hydroxymethyldiphenyl ether (amino alcohol) added to isolated perfused rat liver was rapidly cleared in bile as a mixture of highly polar conjugates, whereas the major route of excretion in vivo was as the 4-, 7- and 9-hydroxylactam sulphates in urine. The lactam of CR was eliminated exclusively in urine giving the same products as obtained for CR, but the distribution of metabolites of the C10-C11 dihydro derivative of CR was unlike that of the parent compound indicating that it occupies only a peripheral role in the fate of CR in vivo. A mixture of 7-, 4- and 9-hydroxylactams derived from the enzymic hydrolysis of urinary sulphates was rapidly removed from blood, sulphated and secreted as sulphates into blood both in vivo and in isolated perfused liver. Little biliary excretion occurred. When the urinary sulphates of the hydroxy lactams were administered i.v. to rats, 70% was eliminated in urine within 1 h; however, if the kidneys were ligated biliary excretion of sulphate was higher (58% in 5 h). After intraduodenal administration of the biliary conjugates of CR metabolism, all of the dose was resorbed to be re-secreted in bile or excreted as sulphates in urine. These studies confirm that the major metabolic fate of CR in the rat is oxidation to lactam, followed by ring hydroxylation, sulphation and urinary excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Differences among humans in steady-state evoked potentials: evaluation of alpha activity, attentiveness and cognitive awareness of perceptual effectiveness.

We examined some of the variables that were possible sources of the wide variability among and within human subjects in their steady-state visual evoked potentials (VEP) in response to continuously counter-phased visual stimuli (vertical bars). We found that within a given subject the magnitude of VEP was reasonably consistent during replicate trials under comparable conditions. However, across subjects there were enormous differences (as much as 17-fold) in the VEP magnitude (i.e. in the spectral power developed at the stimulus reversal frequency). These differences could not be explained by differences among subjects in arousal (alpha activity before or during stimulation), attentiveness (as indicated by reaction times to random cueing), or by a person's subjective impression of his responsiveness to stimulation.

Adult↗

Perceptual distortions in visual-evoked potentials.

We tested ten healthy men, ranging in age from 24 to 55 years, to determine whether "drifting" of a fixation target during pattern-stimulus testing was the result of stimulus-induced ocular movements or a purely perceptual response with no oculomotor basis. We also wanted to learn whether this drifting interfered with the development of the visual-evoked potential. We observed large intersubject differences in visual-evoked potential magnitude that could not be explained by either actual or perceived drifting. Perceived drifting did not correlate with actual or perceived drifting. Perceived drifting did not correlate with actual ocular movements. Moreover, when sporadic ocular movements occurred, they did not interfere with the visual-evoked potential; there were no correlations between magnitude of visual-evoked potential and the percentage of time that drifting was perceived.

Adult↗

Effects of age on acquisition and maintenance of a location discrimination in rats.

Twelve-and thirty-month old Sprague Dawley rats were trained in an auditory discrimination using a discrete trial procedure with food as the reinforcer. Two thirty-month an two twelve-month animals acquired the discrimination in one trail. The asymptotic level of correct responding was lower for the old animals and this was attributed to changes in auditory threshold with age. The thirty-month animals gave more intertrial interval responses than the twelve-month animals. There was no difference in the average response latency for the two age groups.

Aging↗