Biomedical subjects

R G Brown

Publications and source records attributed to R G Brown.

At least 55 records · Page 3Linked to original sources

PubMed1996

Cognitive-motor dysfunction in Parkinson's disease.

Patients with Parkinson's disease (PD) present with a wide range of cognitive and motor dysfunctions. Attempts to fit these deficits into a neuroanatomical framework have tended to emphasise their separateness. This paper, however, takes a broader perspective based on the concept of action-purposeful goal-directed behaviour-which serves to integrate the various deficits into a common framework. Of the motor symptoms of PD, akinesia is chosen as representing a breakdown in a distributed system of action control. Three aspects of akinesia are considered-slowness to initiate movement, slowness to execute movement and poverty of spontaneous movement. All are seen as being surface manifestation of the system's attempts to cope with or adapt to the limitations imposed by the disease process, at a cognitive, motor and integrative level.

Adaptation, Physiological↗

PubMed1995

Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson's disease subjects.

We investigated the functional anatomy of self-initiated and externally triggered movements. Six patients with Parkinson's disease off medication and six age-matched normals were assessed. All subjects had regional cerebral blood flow (rCBF) measurement with PET and recording of movement-related cortical potentials (MRPs) from frontal (F), fronto-central (FC), central (C) and parietal (P) sites to obtain measures of the Bereitschaftspotential (BP). The tasks were (i) self-initiated extension of the right index finger on average once every 3 s, (ii) externally triggered finger extension with the rate yoked to the self-initiated task, and (iii) rest condition with tones presented at a rate yoked with the self-initiated task. For the self-initiated movements, the amplitude of the early and peak BP were lower in Parkinson's disease relative to normals. For the externally triggered movements, the patients and the normals did not differ on any of the measures of cortical negativity prior to movement. For both groups, the late and peak BP components, but not the early component, had a lower amplitude in the externally triggered than the self-initiated movements. In normals, the left primary sensorimotor cortex, the supplementary motor area bilaterally, anterior cingulate, the lateral premotor cortex bilaterally, the insular cortex bilaterally, the left thalamus and the left putamen, parietal area 40 bilaterally and the right dorsolateral prefrontal cortex (DLPFC) were significantly activated during the self-initiated movements relative to rest. For the normals, greater activation of the right DLPFC during the self-initiated movements was the only area that significantly differentiated them from the externally triggered movements. When Parkinson's disease patients and normals were compared for the self-initiated movements relative to rest, normals showed greater activation of the supplementary motor area and anterior cingulate, left putamen, left insular cortex, right DLPFC and right parietal area 40. When the groups were compared for the externally triggered movements relative to rest, the global pattern of blood flow and rCBF change in the two groups did not differ, confirming the absence of group differences in BPs for the externally triggered movements. During the self-initiated movements, the lower amplitude of the early BP in patients with Parkinson's disease as well as the underactivation of the supplementary motor area relative to normals support the premises that (i) the supplementary motor area contributes to the early BP, and (ii) the deficit is self-initiated movements in Parkinson's disease is due to supplementary motor area underactivation. The DLPFC is activated in situations requiring non-routine decision making as in the self-initiated movements.

Aged↗

PubMed1995

Moclobemide twice daily in the treatment of major depressive episode: a double-blind, multicenter comparison with different three times daily dosage schedules.

The data on a twice-daily dosage schedule with moclobemide in the treatment of a major depressive episode (MDE) is limited. In this randomized, double-blind, multicenter study, moclobemide, 150 mg twice daily, was compared with two different three times daily regimens with total daily dosages of 300 and 450 mg, respectively, over a 6-week period. Two hundred seventy patients were included, of whom 237 completed the study. The treatment groups were comparable with respect to demographic parameters and severity of depression at baseline. No clear differences between the treatment groups could be shown with respect to response on the Hamilton Rating Scale for Depression (HAM-D), the Zung Self Rating Scale, or the Clinical Global Impression of efficacy and severity. There was, however, a slightly higher response rate with respect to the anxiety/agitation subscale of the HAM-D in the 150-mg twice-daily group. In all groups, there was a marked and comparable response with respect to suicide ideation. There were no marked differences between the groups with respect to the type and frequency of adverse events. Tolerability was rated "good" or "excellent" in 93% of patients, and there was no appreciable change in blood pressure, pulse rate, or body weight in any of the treatment groups over the study period. The three dosage schedules of moclobemide studied are effective and well tolerated in the treatment of patients with MDE. Moclobemide, 150 mg twice daily, is the optimal initial daily dosage schedule.

Adult↗

PubMed1994

Hyperzincuria in individuals with insulin-dependent diabetes mellitus: concurrent zinc status and the effect of high-dose zinc supplementation.

The urinary excretion of zinc in individuals with insulin-dependent diabetes mellitus (IDDM) is approximately doubled. In the absence of a compensatory mechanism, this hyperzincuria should induce a deficient or marginal Zn status. We examined parameters of Zn status in plasma and in blood cells with respect to urinary Zn losses and Zn supplementation. We measured Zn levels in the urine, plasma, and erythrocytes of 14 IDDM subjects and 15 nondiabetics who kept dietary records for 3 consecutive days. Subsequently, six IDDM subjects and seven nondiabetics were supplemented with 50 mg Zn daily for 28 days. We measured the above parameters, as well as mononuclear leukocyte Zn (MNL-Zn) and the plasma subfraction of albumin-bound Zn (alb-Zn). The total plasma Zn-binding capacity was also assessed. Plasma copper and erythrocyte Cu were monitored as indicators of potential Zn toxicity. Individuals with IDDM displayed the expected hyperzincuria, but had normal blood Zn parameters. Zincuria increased by a similar amount in both groups during supplementation, as did the MNL-Zn content. However, erythrocyte Zn (e-Zn) was refractory, so a trend toward lower e-Zn among IDDM subjects persisted during Zn supplementation. Hemoglobin A1c (HbA1c) increased markedly in the Zn-supplemented IDDM group. Despite their chronic hyperzincuria, individuals with IDDM appear not to be Zn-deficient. Large-dose Zn supplementation increases MNL-Zn and induces an undesirable elevation of HbA1c in all individuals. This is especially disconcerting for those with IDDM, and may reflect an exacerbation of a chronic "Zn diabetes." These data suggest a potential for toxicity from large-dose Zn supplementation.

Adult↗

PubMed1994

Cognitive function in depression: its relationship to the presence and severity of intellectual decline.

Cognitive dysfunction is an integral feature of depression, in some cases of sufficient severity to warrant a diagnosis of dementia. There has been little systematic investigation of whether cognitive dysfunction is an inevitable consequence of depression, or is specific to a subgroup of depressed patients. Related to this is the distribution of cognitive dysfunction, whether there is a continuum of impairment or a distinct demented subgroup. Finally, there is the question of which aspects of cognitive function are most sensitive to the intellectual decline seen in depression. A study is described which addresses these issues. The distribution of global cognition was found to be normally distributed in the sample of 29 patients assessed. Based on this distribution and the scores of a control sample, the patients were classified as unimpaired, borderline or impaired. Two sets of independent comparisons were carried out. First, the unimpaired depressed patients were compared to matched non-depressed controls. Significant deficits were found on a range of neuropsychological measures covering aspects of language function, memory, both recall and recognition, attention and behavioural regulation. These same patients were also compared with two groups of matched depressed patients, with varying degrees of global cognitive impairment. In general, the cognitive measures showed a gradient of dysfunction across the three patients groups. Significant differences between the depressed groups were shown on measures of immediate recall, attention and behavioural regulation. The possible significance of attentional factors for the observed memory dysfunction is discussed.

Adult↗

PubMed1994

Neuropsychological dysfunction in depression: the relationship to regional cerebral blood flow.

The relationship between neuropsychological test performance and regional cerebral blood flow (rCBF) was examined in 29 patients meeting Research Diagnostic Criteria (RDC) for major depression. Following a comprehensive neuropsychological assessment two subsets of tests, comprising tests that discriminated between patients and controls or between patients with varying degrees of global cognitive impairment, were selected. These subtests were entered into a principal components analysis (PCA) which generated a two-factor solution, accounting for 50% of the overall variance in test scores. Individual patient loadings on each of these factors were subsequently correlated with regional cerebral blood flow (rCBF), as measured by positron emission tomography (PET). Both factors demonstrated significant correlations with rCBF in the medial prefrontal cortex and frontal polar cortex while for each factor there were also unique patterns of correlations with posterior brain regions. The findings provide additional evidence that neuropsychological deficits in depression are associated with abnormalities in regional brain function and in particular with the function of the medial prefrontal cortex.

Adult↗

PubMed1994

Vitamin C: an aldose reductase inhibitor that normalizes erythrocyte sorbitol in insulin-dependent diabetes mellitus.

OBJECTIVE: Diabetic hyperglycemia promotes sorbitol production from glucose via aldose reductase. Since the intracellular accumulation of sorbitol, or its sequelae, are postulated to contribute to the progression of chronic diabetic complications, aldose reductase inhibitors (ARI) offer therapeutic promise. Others have shown that vitamin C at pharmacologic doses decreases erythrocyte (RBC) sorbitol. We examined whether smaller, physiologic doses of vitamin C were also effective in individuals with insulin-dependent diabetes mellitus (IDDM) and whether vitamin C was an ARI in vitro. METHODS: Vitamin C supplements (100 or 600 mg) were taken daily for 58 days by young adults with IDDM and nondiabetic adults in an otherwise free-living design. Diabetic control was monitored by fasting plasma glucose, glycosylated hemoglobin, and glycosuria and was moderate to poor throughout the study. RBC sorbitol was measured at baseline and again at 30 and 58 days. Three-day dietary records and 24-hour urine collections were performed for each sampling day. RESULTS: RBC sorbitol levels were significantly elevated in IDDMs, on average doubled, despite their more than adequate dietary intakes of vitamin C and normal plasma concentrations. Vitamin C supplementation at either dose normalized the RBC sorbitol in IDDMs within 30 days. This correction of sorbitol accumulation was independent of changes in diabetic control. Furthermore, our in vitro studies show that ascorbic acid inhibited aldose reductase activity. CONCLUSIONS: Vitamin C supplementation is effective in reducing sorbitol accumulation in the erythrocytes of diabetics. Given its tissue distribution and low toxicity, we suggest a superiority for vitamin C over pharmaceutic ARIs.

Adult↗

PubMed1994

Ouabain enhances the mitogenic effect of serum in vascular smooth muscle cells.

Recently ouabain has been shown to induce transcription of proto-oncogenes in different cell types. In the present study, we examined the effect of ouabain on the proliferation of cultured vascular smooth muscle cells (VSMCs). Primary aortic VSMCs of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, and the rat VSMC cell line A10, were used. Different concentrations of ouabain (10(-9) to 10(-5) mol/L) were added to either quiescent or proliferating cells, and the cell number, the rate of thymidine incorporation into DNA, and the transcription of c-fos and c-myc were examined. The addition of ouabain to proliferating VSMC increased the rate of thymidine incorporation into DNA in a dose-dependent manner, and induced the transcription of the proto-oncogenes within 1 h. This latter response disappeared after 24 h. The number of cells significantly increased in response to low concentrations of ouabain (10(-8) to 10(-7) mol/L), but gradually decreased in response to higher concentrations of the agent, probably due to a toxic effect. Addition of ouabain to quiescent cells, in medium without serum, did not promote cell growth by any of the parameters examined. According to a current theory, endogenous digitalis-like substances possess natriuretic and hypertensive properties, and provide the link between an excessive intake of salt and high blood pressure. The mitogenic effect of ouabain on VSMCs may be a component of this hypertensive action.

Animals↗

PubMed1994

Understanding advertising in pet nutrition.

Advertising is part of the effort to attract attention of consumers to products, in this case, pet foods. It is generally benign in its effect, but it can be misleading, although rarely deliberately so. It uses a specialized vocabulary, which must be mastered if one is to understand what is intended. For all of the expense and effort, advertising figures directly in relatively few decisions to purchase. Its main intention is to call our attention to a particular pet food and to give that product an image. If the pet food does not perform in the consumer's hands, then all of the advertising on earth will not be persuasive. On the other hand, if a product performs well, the word-of-mouth will be positive and that mode of advertising is one of the most effective.

Advertising↗

PubMed1993

Regional cerebral blood flow in depression measured by positron emission tomography: the relationship with clinical dimensions.

We have previously reported focal abnormalities of regional cerebral blood flow (rCBF) in a group of 33 patients with major depression. This report, on an extended sample of 40 patients who demonstrated identical regional deficits to those previously described, examines the relationships between depressive symptoms and patterns of rCBF. Patients' symptom ratings were subjected to factor analysis, producing a three-factor solution. The scores for these three factors, which corresponded to recognizable dimensions of depressive illness, were then correlated with rCBF. The first factor had high loadings for anxiety and correlated positively with rCBF in the posterior cingulate cortex and inferior parietal lobule bilaterally. The second factor had high loadings for psychomotor retardation and depressed mood and correlated negatively with rCBF in the left dorsolateral prefrontal cortex and left angular gyrus. The third factor had a high loading for cognitive performance and correlated positively with rCBF in the left medial prefrontal cortex. These data indicate that symptomatic specificity may be ascribed to regional functional deficits in major depressive illness.

Adult↗

PubMed1993

Disorders of water and sodium balance.

The serum sodium concentration reflects a patient's relative water balance and thus determines if the patient needs more or less water than normal maintenance needs would dictate. The serum sodium concentration has no bearing on whether a patient requires sodium restriction or saline administration. Rather, the sodium/saline balance is determined by clinical assessment of the patient's extracellular fluid volume. Physicians must clearly understand the principles involved when assessing a patient's water and sodium needs. After maintenance water needs and any foreseeable ongoing losses have been factored in, an intelligent plan of fluid management can be initiated. Frequent reassessments, with serial weight measurements, clinical evaluations of extracellular fluid volume status, and determinations of serum sodium concentration, are essential to determine if the desired therapeutic goals are being reached.

Body Fluids↗

PubMed1993

Response choice in Parkinson's disease. The effects of uncertainty and stimulus-response compatibility.

Reaction time paradigms provide a set of methods for assessing aspects of the planning and execution of voluntary movements in Parkinson's disease. Attention has focused mainly on the issue of programming of responses, employing a combination of simple reaction time (SRT) and choice reaction time (CRT) paradigms. The first part of the present study replicated an earlier finding in which patients showed a disproportionate slowing in CRT compared with SRT. The main aim of the study was to investigate the possible role of response choice, a key stage prior to motor programming in this CRT deficit. Two factors were manipulated: (i) response uncertainty and (ii) stimulus-response compatibility. The patients showed a normal increase in reaction time with increasing uncertainty in the compatible conditions, and a normal response to stimulus-response compatibility in the two-choice task. However, the two groups showed qualitatively different patterns of interaction between the two experimental factors, with only the patients showing a disproportionate slowing with incompatible stimulus-response relationships in the four-choice task. The data were interpreted in terms of Hasbroucq et al.'s (1990) list-rule model of stimulus-response compatibility effects, which suggested that the patients and controls were using different strategies for dealing with incompatible stimulus-response relationships. The use of different strategies makes it impossible to determine whether or not the processing of the patients is impaired in Parkinson's disease, although further research is suggested to clarify the question. However, the present data suggest that any impairment in response choice is unlikely to contribute to the slowing in CRT in Parkinson's disease under conditions of high stimulus-response compatibility.

Aged↗

PubMed1993

A comparative study of simple and choice reaction time in Parkinson's, Huntington's and cerebellar disease.

The aim of the study was to compare the quantitative and qualitative similarities and differences in the performance of patients with Parkinson's disease, Huntington's disease and cerebellar disease on a number of reaction time tasks. Simple reaction time (SRT), uncued and fully cued four choice (CRT) tasks were performed by eight patients with Parkinson's disease after withdrawal of dopaminergic medication for an average of 14.4 hours; by seven non-demented patients with Huntington's disease and by eight patients with cerebellar disease. An S1 (warning signal/precue)-S2 (imperative stimulus) paradigm was used in all tasks, with the S1-S2 interval randomly varying between 0, 200, 800, 1600 and 3200 ms across trials. The patients with Huntington's disease had a significantly longer SRT than those with Parkinson's disease. None of the other group differences in uncued and unwarned SRT and CRT was significant. For the patients with Parkinson's disease and those with cerebellar disease, unwarned SRT was faster than uncued and unwarned CRT. For the patients with Huntington's disease, this CRT/SRT difference was not significant. A warning signal before the imperative stimulus resulted in a reduction of reaction time in all three groups. Advance information provided by S1 about the response that would be required by S2 was used by patients in all three groups, evident from reaction times in the fully cued CRT task being faster than those in the uncued CRT condition. Patients with cerebellar disease had slower movement times in the SRT and CRT conditions compared with the patients with Parkinson's disease and Huntington's disease, whose times did not differ. In one SRT condition, when the absence of a warning signal was predictable, patients with cerebellar disease, and to a lesser extent those with Huntington's disease, were able to maintain a general motor readiness before the imperative stimulus. This was not the case for the patients with Parkinson's disease who seemed more dependent on the presence of a warning signal to reduce their reaction time. With a few exceptions, the pattern of results of the three groups were qualitatively similar. It may be concluded that similar reaction time deficits are found in Parkinson's disease, in patients with other disorders of the basal ganglia (Huntington's disease), as well as those with a disease sparing the basal ganglia (cerebellar disease). The non-specific slowness observed at the behavioural level may, however, have diverse central mechanisms.

Adult↗

PubMed1993

The execution of bimanual movements in patients with Parkinson's, Huntington's and cerebellar disease.

Patients with Parkinson's disease have difficulty in performing two different tasks simultaneously. The present study tested whether this deficit was specific to the disease or was found in other patient groups. An identical pattern of performance was shown by a group of patients with cerebellar disease and, to a lesser extent, by a group of patients with Huntington's disease. Further research should focus on clarifying the nature of the deficits and the reasons for the similar performances in the various patient groups.

Female↗

PubMed1993

Cognitive function in hypertension: a community based study.

Cognitive function was investigated in a random sample of subjects on the general practitioners' registry of hypertensive patients in an inner city area and matched with normotensive controls. The response rate was 66% giving 90 matched pairs, average age 63 yrs, with 47% men. There was no difference in educational background or measures of reading ability between the two groups. Cognitive function tests showed a consistent trend of poorer performance in hypertensives, with significant differences in Verbal Learning (immediate recall and retention). Age was inversely related to cognitive function, but no additional deterioration with increasing age was shown in hypertensives.

Adult↗

PubMed1992

The anatomy of melancholia--focal abnormalities of cerebral blood flow in major depression.

Using positron emission tomography (PET) and 15Oxygen, regional cerebral blood flow (rCBF) was measured in 33 patients with primary depression, 10 of whom had an associated severe cognitive impairment, and 23 age-matched controls. PET scans from these groups were analysed on a pixel-by-pixel basis and significant differences between the groups were identified on Statistical Parametric Maps (SPMs). In the depressed group as a whole rCBF was decreased in the left anterior cingulate and the left dorsolateral prefrontal cortex (P less than 0.05 Bonferroni-corrected for multiple comparisons). Comparing patients with and without depression-related cognitive impairment, in the impaired group there were significant decreases in rCBF in the left medial frontal gyrus and increased rCBF in the cerebellar vermis (P less than 0.05 Bonferroni-corrected). Therefore an anatomical dissociation has been described between the rCBF profiles associated with depressed mood and depression-related cognitive impairment. The pre-frontal and limbic areas identified in this study constitute a distributed anatomical network that may be functionally abnormal in major depressive disorder.

Adult↗

PubMed1992

Simple and choice reaction time and the use of advance information for motor preparation in Parkinson's disease.

The effects of different types of advance information (warning signal, temporal cue, movement parameter cue), presented at different intervals before an imperative stimulus on reaction time (RT) were examined. Sixteen patients with Parkinson's disease and 16 age-matched normal controls performed a simple reaction time (SRT) task, an uncued, two partially cued (cueing of direction of movement or hand) and a fully cued visual four choice reaction time (CRT) tasks. An S1-S2 paradigm was used, where a warning signal/precue (S1) preceded the imperative signal (S2) by 0 (uncued and unwarned conditions), 200 ms, 800 ms, 1600 ms or 3200 ms. When the unwarned SRT and uncued CRT conditions were compared, the patients were slower than the controls in both conditions, with the group differences being larger for the CRT than the SRT task. Both patients and controls benefited from a warning signal presented before the imperative stimulus (S2), especially when it occurred 200 ms prior to S2. Advance information about the parameters of the required response was used by both patients and controls to preprogramme responses before the onset of S2. In both groups, RTs were generally faster for longer S1-S2 intervals. With an S1-S2 interval of 3200 ms, advance information about two movement parameters was 'fully' used by the patients to preprogramme responses such that their fully cued CRT was reduced to the level of SRT. In the controls, this process was complete by 800 ms. The most parsimonious explanation of the pattern of results across the SRT, fully cued CRT and uncued CRT conditions would be in terms of a slowness in response initiation in Parkinson's disease, which is a stage of processing common to all RT conditions. Deficits at one or more of the stages of processing unique to CRT are, however, necessary to explain the differentially greater slowness of uncued CRT in Parkinson's disease.

Aged↗

PubMed1992

The effect of withdrawal of dopaminergic medication on simple and choice reaction time and the use of advance information in Parkinson's disease.

Eight patients with Parkinson's disease performed simple reaction time (SRT), uncued, partially and fully cued four choice (CRT) tasks. They were tested on two occasions; on their normal dose of dopaminergic medication and following withdrawal of such medication for an average of 14.4 hours. Disability as rated on the Webster scale was greater in the drug reduced state. Although RTs were generally slower when tested in the drug reduced state than when on medication, few differences emerged. Withdrawal of dopaminergic medication had no effect on unwarned SRT and unwarned and uncued CRT performance. Both on and off medication, the patients benefited from a warning signal presented before the imperative stimulus. In both medication states, the speeding up of RT was greatest with a warning signal presented 200 ms before S2. When the imperative stimulus was unwarned, the temporal predictability of its occurrence speeded RT more when on medication than when off. Advance movement parameter information was used by patients to pre-programme responses both on and off medication. In both medication states, the fully cued CRT was the same as SRT only with the 3200 ms S1-S2 interval. Medication state had no effect on movement time or the number of errors. It is suggested that slowness in motor readiness and motor programming may not be specific to striatal dopamine deficiency but rather a nonspecific concomitant of brain damage.

Adult↗