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Biomedical subjects

A M Owen

Publications and source records attributed to A M Owen.

13 recordsLinked to original sources
PubMed1992

L-dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction.

A group of ten patients with idiopathic Parkinson's disease (PD) was tested on a series of automated tests of learning, memory, planning and attention whilst either on or off L-dopa medication. Controlled withdrawal of L-dopa interfered with aspects of performance on three of the tests that had previously been shown to be sensitive to frontal lobe dysfunction; a spatial working memory task, the Tower of London planning test, and a visual discrimination paradigm that also included intra- and extra-dimensional shift tests of selective attention. More specifically, errors were increased in the spatial working memory test, and both the accuracy and latency of thinking were impaired. Thinking time was significantly slowed following L-dopa withdrawal, even though the possible contaminating effects on motor slowing were fully controlled by a yoked control procedure. Nine out of ten patients reached a further stage of the visual discrimination, set-shifting paradigm when on, rather than off, L-dopa medication. Spatial span was also impaired off medication, but there were no effects of L-dopa withdrawal on tests of pattern and spatial recognition memory, simultaneous and delayed matching to sample or visuospatial conditional associative learning. Comparisons with a large control group confirmed previous findings that PD is associated with deficits on the majority of these tests. The results are discussed in terms of the fronto-striatal, dopamine dependent nature of some of the cognitive deficits found in PD, but the apparent dopamine-independent nature of deficits in other aspects of cognitive functioning, notably in tests of visual recognition memory and associative learning.

Brain Diseases↗
PubMed1992

Cognitive performance in multiple system atrophy.

The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered.

Adult↗
PubMed1992

Fronto-striatal cognitive deficits at different stages of Parkinson's disease.

Groups of patients with idiopathic Parkinson's disease, either medicated or unmedicated, were compared with matched groups of normal controls on a computerized battery previously shown to be sensitive to frontal lobe dysfunction, including tests of planning, spatial working memory and attentional set-shifting. In a series of problems based on the 'Tower of London' test, medicated patients with Parkinson's disease were shown to be impaired in the amount of time spent thinking about (planning) the solution to each problem. Additionally, an impairment in terms of the accuracy of the solution produced on this test was only evident in those patients with more severe clinical symptoms and was accompanied by deficits in an associated test of spatial short-term memory. Medicated patients with both mild and severe clinical symptoms were also impaired on a related test of spatial working memory. In contrast, a group of patients who were unmedicated and 'early in the course' of the disease were unimpaired in all three of these tests. However, all three Parkinson's disease groups were impaired in the test of attentional set-shifting ability, although unimpaired in a test of pattern recognition which is insensitive to frontal lobe damage. These data are compared with those previously published from a group of young neurosurgical patients with localized excisions of the frontal lobes and are discussed in terms of the specific nature of the cognitive deficit at different stages of Parkinson's disease.

Aged↗
PubMed1991

Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man.

Attentional "set" shifting was assessed in a group of 20 neurosurgical patients with localized excisions of the frontal lobes, a group of 20 patients with unilateral temporal lobe lesions and a group of 11 patients who had undergone amygdalo-hippocampus removal. These three patient groups were compared with groups of both young (age-matched) and elderly normal control volunteers on a computerized test of visual discrimination learning involving both an intra- and an extra-dimensional shift. The frontal lobe group were selectively impaired in their ability to shift response set to a previously irrelevant dimension but not to shift attention to new exemplars of a previously relevant dimension. A similar pattern was observed in the elderly group of normal control volunteers. By comparison, both the temporal lobe patients and the amygdalo-hippocampectomy patients were unimpaired in their ability to perform either shift, although both groups had significantly prolonged selection latencies at the extra-dimensional shift stage of the task. These data are compared to previous findings from patients with idiopathic Parkinson's disease and are discussed in terms of a specific attentional set shifting deficit following frontal lobe damage.

Adult↗
PubMed1991

Psychiatric, neurological and medical aspects of misidentification syndromes: a review of 260 cases.

Two hundred and sixty case reports of misidentification syndromes were evaluated. One hundred and seventy-four patients had a Capgras syndrome misidentifying other persons, 18 a Fregoli syndrome, 11 intermetamorphosis, 17 reduplicative paramnesia and the rest had other forms or combinations of mistaken identification. Schizophrenia (127 cases), mostly of paranoid type, affective disorder (29), and organic mental syndromes including dementia (46) were the most common diagnoses in patients who misidentified others or themselves. The patients with reduplicative paramnesia more frequently suffered from head trauma or cerebral infarction and showed more features of right hemisphere lesions on neuropsychological testing or CT scan than the patients with other misidentification syndromes. Forty-one case-reports implicated underlying medical conditions. Forty-six of the patients were reported to show violent behaviour. The misidentification of persons can be a manifestation of any organic or functional psychosis, but the misidentification of place is frequently associated with neurological diseases, predominantly of the right hemisphere. Misidentification syndromes show a great degree of overlap and do not represent distinctive syndromes nor can they be regarded as an expression of a particular disorder. These patients deserve special diagnostic and therapeutic attention because of the possible underlying disorders and their potentially dangerous behaviour.

Adult↗
PubMed1991

Mailed dietary surveys: response rates, error rates, and the effect of omitted food items on nutrient values.

Mailed surveys may be a cost-effective way to collect dietary information in large populations. We sent a brief quantified food frequency survey to a random sample of 2,000 prepaid health plan members between the ages of 20 and 65 years for two consecutive years. Logistic regression was used to predict the probability of: (1) responding to the questionnaire, (2) completing all 60 items in the questionnaire correctly so that all information could be used (responding entirely correctly), and (3) completing all 60 items in the questionnaire incorrectly so that no information was usable (responding entirely incorrectly). In a follow-up survey of a subsample of respondents, Spearman correlation coefficients were used to compare nutrient intakes calculated from questionnaires that had omitted data with those from the same questionnaires after the missing information was completed by telephone interview. About 50% of all persons surveyed returned the questionnaire. Response rates were highest among persons who had taken a voluntary multiphasic health examination, among women, and among older persons. Only 22.9% of the respondents in year 1 and 27.7% of the respondents in year 2 responded entirely correctly; a small percentage of respondents (12.1%) omitted more than 10 food items. Responding entirely correctly was inversely related to age and related to race. Most correlations between nutrient intakes calculated from questionnaires with omitted data and those from the same questionnaire subsequently completed by telephone interview were greater than 0.90 and increased as the number of omitted items decreased. If a relatively low overall response rate is acceptable, food frequencies collected through the mail can be an effective way to gather dietary information.

Adult↗
PubMed1990

Effect of treatment with 4-hydroxyandrostenedione on the peripheral conversion of androstenedione to estrone and in vitro tumor aromatase activity in postmenopausal women with breast cancer.

The effect of treatment with the aromatase inhibitor, 4-hydroxyandrostenedione (4-OHA) on the peripheral conversion of androstenedione to estrone has been examined in eight postmenopausal women with advanced breast cancer. Before treatment conversion of androstenedione to estrone ([p]AEIBB) ranged from 0.81 to 3.7% and was almost completely inhibited after treatment with 4-OHA (two doses of 500 mg i.m. with an interval of 12 days between doses). Transfer constants were also measured by the urinary method ([p]AEIBU) for some subjects and decreased from 2.3 +/- 0.52% to 0.24 +/- 0.11% after treatment, a mean reduction of 90%. Mean plasma concentration of estradiol (37.4 +/- 16.6 pmol/liter) and estrone (99.0 +/- 32.2 pmol/liter) decreased significantly (P less than 0.01) to 15.7 +/- 4.6 pmol/liter and 52.4 +/- 8.9 pmol/liter, respectively, after treatment. Aromatase and DNA polymerase alpha (a marker of cell proliferation) activities were measured in seven samples of breast tumor tissue obtained before and after treatment. For three samples there was a marked (67 +/- 17%) decrease in tumor aromatase activity after treatment, for two, little change occurred, while tumor aromatase activity in the other two samples appeared to be resistant to the effect of 4-OHA. The correlation between tumor aromatase and DNA polymerase alpha activities (r = 0.45) failed to reach a significant level.

Aged↗
PubMed1990

Microdochectomy for discharge from a single lactiferous duct.

Microdochectomy for persistent discharge from a single lactiferous duct was performed in 162 women. Invasive or in situ ductal carcinoma was diagnosed in 16 patients (10 per cent), none of whom had a palpable lump. The discharge was blood-stained in 14 of these women and in two it was clear. Mammography was performed in 15 of these 16 patients and was abnormal in only five. Three patients had atypical ductal hyperplasia, one of whom subsequently developed an invasive ductal carcinoma. Microdochectomy for persistent discharge from a single lactiferous duct is curative and gives a diagnosis of the cause. It remains the treatment of choice whether the discharge is blood-stained or clear.

Adolescent↗
PubMed1990

Planning and spatial working memory following frontal lobe lesions in man.

Twenty-six patients with unilateral or bilateral frontal lobe excisions were compared with age and IQ matched controls on a computerized battery of tests of spatial working memory and planning. A computerized test of spatial short term memory capacity revealed no significant impairment in the patients' ability to execute a given sequence of visuo-spatial moves. In contrast, a paradigm designed to assess spatial working memory capacity, revealed significant impairments in the patient group in both possible types of search errors. Furthermore, additional analysis showed that the frontal lobe patients were less efficient than controls in their usage of a strategy for improving performance on this test. Higher level planning was also investigated using a test based on the "Tower of London" problem [SHALLICE, T. Phil. Trans. R. Soc. Lond. B. 298, 199-209, 1982]. Patients with frontal lobe damage required more moves to complete the problems and a yoked motor control condition revealed that movement times were significantly increased in this group. Taking both of these factors into consideration, initial thinking (planning) time was unimpaired in the patient group although the thinking time subsequent to the first move was significantly prolonged. These data are compared to previous findings from patients with idiopathic Parkinson's disease and are discussed in terms of an impairment of higher cognitive functioning following frontal lobe damage.

Attention↗
PubMed1989

In situ oestrone synthesis in normal breast and breast tumour tissues: effect of treatment with 4-hydroxyandrostenedione.

An isotopic infusion technique has been used in an attempt to determine the contribution that local, in situ, oestrone synthesis makes to the oestrogen content of breast tumours. 3H-Androstenedione and 14C-oestrone were infused into women with advanced breast cancer for 12 hr before operation. At surgery, normal breast and breast tumour biopsy samples were obtained and 3H-androstenedione, 3H-oestrone derived from 3H-androstenedione and 14C-oestrone were isolated and measured. DNA polymerase alpha activity, a marker of cellular proliferation, was also measured to examine whether local synthesis of oestrone exerted a biological effect. The study was repeated after patients had been treated with the aromatase inhibitor, 4-hydroxyandrostenedione, before undergoing further surgery for removal of their tumours. In 4/6 tumours examined, in situ synthesis of 3H-oestrone from 3H-androstenedione accounted for the major part (84.3 +/- 9.0%) of the 3H-oestrone detected, while no significant in situ synthesis occurred in 2 other tumours. Although treatment with 4-hydroxyandrostenedione did not significantly alter the uptake of 3H-androstenedione or 14C-oestrone into breast tissues, in situ formation of 3H-oestrone was only detected in one tumour sample after treatment. DNA polymerase alpha activity decreased in 4/6 tumours after treatment with 4-hydroxyandrostenedione. Overall, however, there was no significant correlation between the level of 3H-oestrone formed in situ and DNA polymerase alpha activity (r = 0.38, NS). It is concluded that in some, but not all, breast tumours in situ formation of oestrone can make an important contribution to the oestrogen content of breast tumours.

Aged↗
PubMed1989

Adriamycin action on human breast cancer cells: enhancement by medroxyprogesterone acetate.

Exposure of cultured human breast cancer cells (MCF-7) to medroxyprogesterone acetate (MPA) prior to treatment with adriamycin (ADR) enhanced the effect of the cytotoxic drug on cell yield after further growth of viable cells. Pretreatment with oestradiol (E2) produced similar synergism, but no such effect was observed using dexamethasone. Exposure to ADR before MPA led to an additive effect, but not to synergism. When cells resistant to the growth-inhibitory action of MPA were examined, progestogen/drug synergism could still be demonstrated. We conclude that the effects of ADR, like those of methotrexate and vincristine, can be enhanced by pre-treatment with MPA and that further clinical trials of such a regimen are needed.

Antineoplastic Agents↗
PubMed1989

Actions of medroxyprogesterone acetate on the efficacy of cytotoxic drugs: studies with human breast cancer cells in culture.

Human breast cancer cells (MCF-7) showed increased responses to methotrexate and vincristine after a 48-hr pre-treatment with medroxyprogesterone acetate. The effect of the hormone, which was detectable at concentrations of between 10 and 100 nM, was independent of its growth-inhibitory action. These findings confirm a previous clinical study and have important implications with regard to the management of advanced breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗