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Biomedical subjects

M W Brown

Publications and source records attributed to M W Brown.

At least 55 records · Page 3Linked to original sources

Parental perceptions of barriers to childhood immunization: results of focus groups conducted in an urban population.

The current US immunization rates for 2 year olds are approximately half of the goal set for the year 2000. Research studies have focused primarily on the perception of health care providers in the identification of barriers and benefits to childhood immunization. While health care providers are an important part of the immunization delivery process, the perceptions of parents are also important. In this study, qualitative methods were used to explore perceived parental barriers to childhood immunization delivery. Twelve focus groups comprising White, African-American, Hispanic, urban and non-urban people were conducted at a variety of sites, including clinics, churches, schools and work sites. The results indicated that time off from work, access to well-child care and difficulty understanding the complexity of the immunization schedule were seen as barriers to adhering to an immunization schedule. Participants emphasized problems in taking time off from work to get immunizations, sometimes without pay, and expressed fears that doing so would jeopardize promotions and raises. While some of the parental perceptions were similar to those identified in studies of health care providers in the literature, many were not. This study emphasizes the importance of gathering information from parents as well as from health care providers.

Attitude to Health↗

Differential effects of beta-blockers in patients after recovery from myocardial infarction and after recovery from unstable angina. Multicenter Myocardial Ischemia Research Group.

We examined the effect of beta-blockers on outcome in patients enrolled in the Multicenter Study of Myocardial Ischemia. We started prospective enrollment of patients after an acute coronary event (acute myocardial infarction [MI] or unstable angina) in North America, Israel, and Japan from mid-1988, and followed-up the 1042 patients for 6-43 months (average, 26 months); 47.2% of the patients were receiving beta-blockers at baseline. Overall, beta-blockers were associated with neutral effects on the chronic outcome: the cardiac event (cardiac death or recurrent nonfatal MI) rate was 6.8% for patients on beta-blockers and 7.5% for those who were not on beta-blockers (P = 0.72). However, a significant interaction (P = 0.018) was found between event type and the use of beta-blockers in regard to the cardiac event rate. That is, beta-blockers were associated with a lower risk of the cardiac event for patients whose index event type was MI (risk ratio, 0.59) in contrast to those whose index event was unstable angina (risk ratio, 1.92). The chronic use of beta-blockers in patients recovered from unstable angina may be associated with an increase in risk.

Adrenergic beta-Antagonists↗

Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators.

BACKGROUND: Unsustained ventricular tachycardia in patients with previous myocardial infarction and left ventricular dysfunction is associated with a two-year mortality rate of about 30 percent. We studied whether prophylactic therapy with an implanted cardioverter-defibrillator, as compared with conventional medical therapy, would improve survival in this high-risk group of patients. METHODS: Over the course of five years, 196 patients in New York Heart Association functional class I, II, or III with prior myocardial infarction; a left ventricular ejection fraction < or = 0.35; a documented episode of asymptomatic unsustained ventricular tachycardia; and inducible, nonsuppressible ventricular tachyarrhythmia on electrophysiologic study were randomly assigned to receive an implanted defibrillator (n = 95) or conventional medical therapy (n=101). We used a two-sided sequential design with death from any cause as the end point. RESULTS: The base-line characteristics of the two treatment groups were similar. During an average follow-up of 27 months, there were 15 deaths in the defibrillator group (11 from cardiac causes) and 39 deaths in the conventional-therapy group (27 from cardiac causes) (hazard ratio for overall mortality, 0.46; 95 percent confidence interval, 0.26 to 0.82; P=0.009). There was no evidence that amiodarone, beta-blockers, or any other antiarrhythmic therapy had a significant influence on the observed hazard ratio. CONCLUSIONS: In patients with a prior myocardial infarction who are at high risk for ventricular tachyarrhythmia, prophylactic therapy with an implanted defibrillator leads to improved survival as compared with conventional medical therapy.

Adult↗

Mapping visual recognition memory through expression of the immediate early gene c-fos.

To study brain regions involved in familiarity discrimination, rats were shown sets of novel and familiar objects. On each trial two objects were shown simultaneously to a rat so that one eye saw a novel object while the other saw a familiar object. Thus novel and familiar objects were seen with the same conditions of alertness and eye movements. Activated neurones were revealed by staining for products of the immediate early gene c-fos. Familiar stimuli activated significantly fewer neurones than novel stimuli in perirhinal cortex and area TE of temporal cortex, and the ventral lateral geniculate nucleus of the thalamus, but not in the hippocampus or other areas sampled. These findings are discussed in relation to recognition memory.

Animals↗

Detection and significance of myocardial ischemia in women versus men within six months of acute myocardial infarction or unstable angina. The Multicenter Myocardial Ischemia Research Group.

Ischemia detection after an acute coronary event predicts subsequent cardiac events. However, gender-related aspects in the prevalence and prognostic significance of ischemia detection after an acute coronary event have not been reported. Noninvasive tests, which included resting 12-lead electrocardiogram (ECG), 24-hour ambulatory ECG, exercise ECG, and thallium-201 stress scintigraphy were performed in 936 stable patients (224 women and 712 men) 1 to 6 months (average 2.7) after an acute coronary event (i.e., myocardial infarction or unstable angina). Primary end points during an average follow-up of 23 months included cardiac death, nonfatal myocardial infarction, and unstable angina, while restricted end points included the first 2. Ischemia detection was significantly less frequent among women than among men on 24-hour ambulatory ECG, exercise ECG, and thallium-201 stress scintigraphy. Primary end points occurred in 19.2% of women and in 19% of men, and restricted end points occurred in 5.8% of women versus 8%. of men (p = NS). Cox analyses revealed that gender and its interaction with each of the ischemia tests did not contribute to the prediction of the primary or restricted end points. We conclude that in stable patients 1 to 6 months after an acute coronary event, ischemia detection by noninvasive tests was significantly less prevalent in women than in men. However, subsequent cardiac event rates in women were similar to those observed in men, and there was no gender-ischemic detection interaction regarding subsequent events.

Angina, Unstable↗

Comparison between Japan and North America in the post-hospital course after recovery from an acute coronary event.

We compared the post-hospital prognosis after an acute coronary event (acute myocardial infarction and unstable angina) in 106 patients in Japan vs. 789 patients in North America who were prospectively enrolled in the Multicenter Study of Myocardial Ischemia and were followed-up for an average of 26 months per patients. Risk factors more frequent in Japan were older age, males and smoking at enrollment, but the rest of many risk factors were similar. After adjusting for differences in clinical and medication variables, Cox analyses indicated patients in North America had a significantly greater risk of experiencing a primary end-point (cardiac death, non-fatal myocardial infarction or unstable angina) than patients in Japan (hazard ratio [North America:Japan] = 3.1, P = 0.003). There was a non-significant trend in the restricted end-points (cardiac death or non-fatal myocardial infarction) with North America having more frequent events than Japan (hazard ratio = 2.2, P = 0.12). The long-term outcome after recovery from an acute coronary event is more favorable in Japan than in North America, mostly due to a reduction in subsequent hospitalization for unstable angina. The reason for these findings cannot be explained by differences in the measured risk factors or medications.

Adult↗

Changes in neuronal activity related to the repetition and relative familiarity of visual stimuli in rhinal and adjacent cortex of the anaesthetised rat.

Employing the same techniques as have been used with conscious rats, this study describes neuronal responses signalling information concerning the prior occurrence of visual stimuli in unconscious rats. Recordings of the activity of 387 neurons were made while anaesthetised rats were shown objects. Changes in neuronal responses related to stimulus repetition and the relative familiarity of visual stimuli were sought. The areas sampled were lateral occipital cortex, area TE of temporal cortex, perirhinal cortex and the hippocampal formation. The response to the first presentations of unfamiliar objects was significantly different from that to their second presentations for 30 (35%) of 86 visually responsive neurones; for 23 of the neurones the response was smaller when the stimulus was repeated, whereas for 7 it was larger. For all of these neurones the response change was maintained across intervening trials on which other stimuli were shown. For 4 (25%) of 16 neurones so tested, the response decrement persisted across at least 10 intervening trials. The activity of 63 neurones was recorded while rats were shown highly familiar as well as unfamiliar objects. The response to unfamiliar objects was significantly different from that to highly familiar objects for 3 (23%) of 13 visually responsive neurones. The types of neuronal response and their incidence expressed as a proportion of the number of visually responsive neurones were similar to those found in unanaesthetised rats (though the proportion of visually responsive neurones encountered in the anaesthetised rat was lower). The results indicate that information concerning the prior occurrence of stimuli is processed even under anaesthesia.

Analysis of Variance↗

Neuronal signalling of information important to visual recognition memory in rat rhinal and neighbouring cortices.

This study was conducted to discover whether the rat cortex contains neurons that signal information concerning the previous occurrence of stimuli, as has been found in the primate. Recordings of the activity of 396 single neurons were made while unanaesthetized rats were shown objects. The effects on neuronal responsiveness of stimulus repetition and of the relative familiarity of the stimuli were sought. The areas sampled were the rhinal (entorhinal and perirhinal) cortex, area TE of the temporal cortex, the lateral occipital cortex and the hippocampal formation. The response to the first presentations of objects was significantly different from that to their second presentations for 63 (34%) of the 185 responsive neurons; for 39 of the neurons the response was smaller when the stimulus was repeated, whereas for 24 it was larger. The incidence of decremental responses was higher in the non-hippocampal cortex than in the hippocampal formation, while the incidence of incremental responses was higher in the hippocampal formation than other cortical areas. The response to unfamiliar objects was significantly different from that to highly familiar objects for 15 (22%) of 67 responsive neurons so tested; for 12 of the neurons the response was smaller when the stimulus was repeated, and for three it was larger; most of these neurons were found in area TE. The responses of ten familiarity neurons varied significantly with the relative familiarity of the stimuli but not with stimulus repetition; the responses of seven recency neurons varied significantly upon stimulus repetition but not with the relative familiarity of the stimuli. Thus information concerning stimulus repetition and familiarity is separably encoded at the single neuron level in the rat cortex. The results demonstrate that in the rat cortex as in the monkey cortex there are neurons that signal information concerning the prior occurrence of stimuli; such information is of importance to recognition memory, working memory and priming memory.

Animals↗

Neurophysiological investigations of a recognition memory system for imprinting in the domestic chick.

The responsiveness of neurons in a region of the chick brain involved in the learning process of imprinting, the right intermediate and medial hyperstriatum ventrale (right IMHV), has been investigated in unanaesthetized, trained and untrained chicks. The results demonstrate that neuronal responsiveness in this region reflects a variety of behavioural consequences of imprinting and is markedly altered as a result of the learning process. Groups of chicks (nine in each group) were either dark-reared or trained (imprinted) by exposure to a rotating red box or a rotating blue cylinder. Recordings of single or small groups of neurons were subsequently made from 156 sites in the right IMHV while the 2-day-old chicks were free to move in a running wheel. There was a highly significant increase in the proportion of sites responsive to the stimulus used to train the birds compared to the proportion responsive to that stimulus in dark-reared birds (30 and 9% respectively). These changes were found when either the red box or the blue cylinder was used to train the bird, the changes being similar for both stimuli. There was also a significant increase in the mean magnitude of the change in neuronal activity on stimulus presentation for the training stimulus compared to the same stimulus when not used in the bird's training. No significant effects of the training experience of the chicks were found upon either the magnitude of evoked activity or the proportion of sites responsive to a rotating stuffed jungle fowl or the sound of the maternal call. The presence of the training stimulus was selectively signalled by the response at certain sites. At other sites there was response generalization across stimulus shape or colour. A comparison with results for the left IMHV demonstrates both similarities and differences in neuronal responsiveness between the two regions. In both regions imprinting selectively enhances neuronal responsiveness to the training stimulus. However, for trained birds the mean proportion of sites responding to whichever of the red box or the blue cylinder was not used in the bird's training was significantly lower in the right than the left IMHV. These results are discussed in relationship to previously reported asymmetries in the response of the right and left IMHV regions to imprinting. A model is introduced to explain the physiological findings. The effects of training on right IMHV neuronal function are consistent with a long-term role for this region in the recognition memory of imprinting.

Acoustic Stimulation↗

Effects of the novelty or familiarity of visual stimuli on the expression of the immediate early gene c-fos in rat brain.

To investigate substrates of recognition memory, the cellular expression of Fos protein in rat brain has been studied after groups of rats were either shown sets of novel or highly familiar objects, or were exposed to the same pattern of illumination without objects being shown. Counts of stained nuclei were made in eight brain regions, where information about novel or familiar visual stimuli is likely to be processed or stored. The counts were relatively high in occipital visual association cortex and area TE of temporal cortex, intermediate in perirhinal cortex, entorhinal cortex, anterior cingulate cortex and the diagonal band of Broca, and low in the hippocampal formation and mediodorsal nucleus of the thalamus. The number of Fos-stained cells was significantly higher for the rats shown novel objects than for those shown familiar objects in perirhinal cortex, area TE, occipital cortex and anterior cingulate cortex. Arguments are advanced that these differences in counts indicate areas involved in the processing and/or storage of information about the novelty or familiarity of visual stimuli, information important to recognition memory.

Animals↗

The effect of cryptolepine on the morphology and survival of Escherichia coli, Candida albicans and Saccharomyces cerevisiae.

The antimicrobial activity of the indoloquinoline alkaloid, cryptolepine, isolated from Cryptolepis sanguinolenta (Fam. Periplocaceae) was determined against selected micro-organisms. The minimum inhibitory concentration (MIC) ranges obtained, expressed as microgram ml-1, were: 5-10 for Saccharomyces cerevisiae NCPF 3139; 10-20 for S. cerevisiae NCPF 3178; 20-40 for Escherichia coli NCTC 10418; 40-80 for E. coli NCTC 11560, Candida albicans ATCC 10231 and C. tropicalis NCPF; and 80-160 for C. albicans NCPF 3242 and NCPF 3262. Biocidal effects were noted at concentrations 2-4 times those of the MIC of the alkaloid following challenge with 10(6) cfu ml-1 of micro-organisms. Time-kill studies showed a reduction in viable count from 10(6) to < 10 cfu ml-1 in 4 h in C. albicans ATCC 10231 exposed to 320 micrograms ml-1 of the agent; 3 log cycle reductions were recorded for the 6 h counts of E. coli NCTC 10418 and S. cerevisiae NCPF 3139 exposed to 40 micrograms ml-1 and 160 micrograms ml-1 of the alkaloid respectively. These results were consistent with findings using scanning electron microscopy. Exposure of cells to biocidal concentrations of cryptolepine produced filamentation prior to lysis in E. coli NCTC 10418 and extreme disturbance of surface structure, including partial and total collapse, followed by lysis in C. albicans ATCC 10231 and S. cerevisiae NCPF 3139.

Alkaloids↗

Learning-related alterations in the visual responsiveness of neurons in a memory system of the chick brain.

The intermediate and medial hyperstriatum ventrale (IMHV) of the chick brain is known to be essential for the learning process of imprinting. The activity of neurons was recorded from the left IMHV of 2-day-old unanaesthetized chicks while the chicks were free to move in a running wheel. The chicks were either raised in complete darkness or visually trained (imprinted) with a set duration of exposure to a visual image. The first group of these birds was trained by exposure for 100 min to a rotating red box and the second was trained by similar exposure to a rotating blue cylinder. A third group was left untrained. Training more than doubled the proportion of sites that responded to the stimulus used to train the bird, relative to the proportion of sites responsive to the other stimulus and to the proportion of sites responsive in the untrained birds; the learning-related increase was selective and highly significant. Behavioural monitoring indicated that the enhanced responsiveness could not be explained by overt differences in the alertness, attentiveness or movements of the birds. No significant effect of training was found on the proportion of sites responsive to a rotating stuffed jungle fowl or to the sound of a maternal call. The response at certain sites selectively signalled the presence of the training stimulus, while at others the response showed generalization across stimulus shape or colour. There was a non-specific effect of training upon the pattern of spontaneous discharges of the neurons: the numbers of spikes occurring in clusters (bursts) was significantly reduced in trained birds compared with the dark reared controls.

Acoustic Stimulation↗

Relation between myocardial infarct location and stroke.

OBJECTIVES: We sought to compare the likelihood of stroke in patients with anterior versus nonanterior myocardial infarction. BACKGROUND: The association between anterior infarction and left ventricular thrombus has led to the assumption that embolization from thrombi is an important cause of stroke in patients with anterior infarction. We hypothesized that if anterior infarction is a cause of left ventricular thrombi, the number of strokes should be disproportionately higher in patients with anterior than nonanterior infarction. METHODS: We performed a retrospective analysis of 2,466 patients randomized from day 3 to day 15 after infarction as part of a multicenter placebo-controlled study of diltiazem to prevent cardiac death or myocardial infarction. Any acute focal cerebral disorder resulting in localizing findings characterized as a stroke or transient ischemic attack was considered an event. RESULTS: Of 91 events during a follow-up period of 12 to 52 months, 23 (3.2%) occurred in 724 patients with an anterior and 68 (3.9%) in 1,742 patients with a nonanterior myocardial infarction (relative risk 0.81; 95% confidence interval 0.51 to 1.30). Power analysis revealed that the negativity of the study was not the result of inadequate sample size. Life table analysis showed no difference in cumulative event rate (p = 0.42) according to site of infarction. Cox regression analysis showed that of 10 clinical covariates, only systolic blood pressure was predictive of stroke (p < 0.001). The use of warfarin did not contribute to the model. Finally, the addition of site of infarction (anterior vs. nonanterior) did not contribute significantly to the Cox model. CONCLUSIONS: Although there is a significant incidence of stroke after acute myocardial infarction, there is no relation between the occurrence of stroke and site of infarction. These data do not support the presumed causal relation between anterior myocardial infarction, thrombus and stroke.

Adult↗

Neuronal activity related to visual recognition memory: long-term memory and the encoding of recency and familiarity information in the primate anterior and medial inferior temporal and rhinal cortex.

Recordings of the activity of 2705 single neurones were made in entorhinal and perirhinal cortex, area TG of the temporal lobe, and the inferior temporal cortex both during monkeys' performance of a serial recognition memory task using complex pictures and when monkeys were shown objects. Responses of 120 (9.7%) of the visually responsive neurons recorded were significantly smaller to the second than to the first presentations of unfamiliar stimuli. The incidence of such responses was highest in perirhinal cortex plus areas TE1 and TE2 of the temporal lobe, intermediate in lateral entorhinal cortex and areas TE3 and TG, and lowest in other parts of entorhinal and inferior temporal cortex. Response decrements were maintained across 20 or more intervening presentations of other stimuli for the majority of the neurones tested. Responses of 43 (14.4%) of the visually responsive neurones tested were significantly greater to unfamiliar than to highly familiar stimuli. Such differential responses were found only in lateral entorhinal and perirhinal cortex plus areas TG, TE1, TE2 and TE3. For 6 neurones the response difference was significant even when the familiar stimuli had not been seen for more than 24 h: such neurones demonstrate access to information stored in long-term memory for more than 24 h. Seven familiarity neurones signalled information concerning the relative familiarity of stimuli but not information concerning how recently they were last seen; 58 recency neurones signalled information concerning the recency of presentation of stimuli, but not their relative familiarity. Thus certain neurones demonstrate the separable encoding of recency and familiarity information. Neurones signalling information of use for recognition memory are found in cortex close to the rhinal sulcus where lesions result in major deficits in the performance of recognition memory tasks. The conjunction of these findings provides strong evidence for the importance of these neurones and this cortex for processes (recency and familiarity discrimination) necessary for recognition and working memory. The possible relation of the neuronal responses to priming memory is also discussed.

Animals↗

Memory loss during pregnancy.

OBJECTIVE: To investigate possible impairment of memory during pregnancy. DESIGN: The performance of pregnant women in a variety of tests of memory was compared to that of controls. SETTING: The Bristol Maternity Hospital. SUBJECTS: Forty-eight volunteer pregnant women attending for routine antenatal checks were compared to 19 nonpregnant controls. MAIN OUTCOME MEASURES: Subjectively perceived rating of memory impairment, objective measures of recall, recognition and priming memory. RESULTS: Pregnant and control groups were given a series of tests of memory at the end of which they were asked to rate their own memory at present compared to some weeks ago (when they were not pregnant). Of the pregnant women 39 out of 48 (81%) rated their current memory as being impaired; only three out of 19 (16%) of the control subjects did so. Objective tests revealed that the pregnant group was significantly impaired in the recall of lists of words, particularly when learning was incidental rather than explicit. The pregnant group was also significantly impaired in two measures of priming memory. No significant deficit was found in recognition. The deficits were found for both primigravid and multigravid women, and were present in all trimesters of pregnancy. CONCLUSIONS: The majority of women believe their memory to be impaired during pregnancy. Objectively, during pregnancy there is significant impairment of memory as tested by recall or by priming, but not by recognition. The pattern of memory loss differs from that of other amnesic conditions. Information imparted to pregnant patients may not be retained as well as might be expected.

Adult↗