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Biomedical subjects

A Evans

Publications and source records attributed to A Evans.

At least 307 records · Page 17Linked to original sources
PubMed1993

Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.

L-Dopa is metabolized to 3-O-methyldopa (3OMD) by catechol-O-methyltransferase (COMT). This reduces the amount of L-dopa available for entry into brain. We studied the effect of OR-611, a new COMT inhibitor, on plasma and brain 6-[18F]-fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methylfluorodopa (3OMFD). PET measurements of striatal 6FD concentrations showed an average 2.3-fold increase following OR-611 pretreatment, compared to the same animals in the control state. OR-611 inhibits plasma metabolism of 6FD and increases brain uptake of this L-dopa analog. OR-611 appears to be a promising agent as an adjunct to L-dopa for the treatment of patients with Parkinson's disease.

Animals↗
PubMed1993

Overnight urine growth hormone, cortisol and adenosine 3' 5' cyclic monophosphate excretion in children with chronic asthma treated with inhaled beclomethasone dipropionate.

Overnight urine samples were obtained from 34 asthmatic children, 24 of whom were receiving inhaled beclomethasone dipropionate (BDP), and 30 controls. The urine volume of the children receiving inhaled steroids was significantly greater than that of the other asthmatic children and of the controls (P < 0.05). Urine growth hormone was within the normal range for all of the subjects and there was no demonstrable relationship between urine growth hormone and height or height standard deviation score. Urine steroid output was significantly reduced in the BDP receiving group when the results were expressed in U l-1 but there was no difference between the groups when the results were expressed per specimen. Urine adenosine 3' 5' cyclic monophosphate (cAMP) results were similar for all groups. We conclude that use of BDP increases overnight urine volume but, in our study, does not appear to influence the output of urine cortisol. Urine free cortisol measurements may not be a very sensitive tool for the detection of small changes in endogenous steroid production. The use of BDP does not adversely affect the output of urine growth hormone.

Administration, Inhalation↗
PubMed1993

Efficient bacterial export of a eukaryotic cytoplasmic cytochrome.

The soluble core domain of cytochrome b5 of liver endoplasmic reticulum was appended at its amino terminus to full-length alkaline phosphatase secretory signal sequence including the ribosomal binding site. The chimeric precursor gene was placed under the transcriptional control of the native pho promoter in a prokaryotic expression vector. Induction of Escherichia coli by growth in a phosphate-limited medium resulted in abundant synthesis of cytochrome b5 as detected spectrophotometrically and by visual transformation of the bacteria to a pink color. The signal-appended cytochrome b5, but not the corresponding signal-deficient derivative, was translocated across the bacterial inner membrane and processed to yield authentic, haem-assembled cytochrome b5 within the periplasm. The eventual processing of the chimeric cytochrome b5 precursor was unusual regarding the known reaction specificity of signal peptidase. The exported, mature haemoprotein was biochemically indistinguishable from its native mammalian counterpart. At peak induction, approximately 6 mg of correctly matured cytochrome b5 per liter of culture was exported. This amount of cytochrome b5 constituted 6% (w/w) of the periplasmic protein. The appearance of the exported apo-cytochrome b5 preceded the formation of holo-protein. Thus the eukaryotic cytoplasmic protein was efficiently exported from E. coli and post-translocationally modified to generate a functional haemoprotein in the periplasm.

Amino Acid Sequence↗
PubMed1993

A study of the referral decision in general practice.

The applicability of published models of the referral decision in general practice was investigated by asking general practitioners (GPs) to record data on consultations during which referral to a consultant's outpatient clinic was considered, whether this resulted in referral or not. The GPs were then interviewed about their decisions with particular reference to patient factors, clinical factors, their perception of the risk involved, consultant factors and time factors. The doctors varied in the weight that they gave to the patient's wishes, and also in their selection and interpretation of diagnostic data. Risk to the patient was rarely a major consideration; neither was risk to the doctor's self-esteem. There was virtually no evidence of conflict arising during the decision-making process, and doctors on the whole, did not feel pressed for time. This was, however, a self-selected sample of highly motivated general practitioners. It is suggested that the assumptions on which the conflict model of decision-making is based do not apply to the majority of referral decisions in general practice.

Adolescent↗
PubMed1993

Sleep related hypoxaemia in hypertensive and normotensive men.

BACKGROUND: An association between hypertension and obstructive sleep apnoea (OSA) has been found by some researchers but remains controversial. Since such an association would have important implications for the investigation and management of hypertension, the rate of nocturnal hypoxaemic episodes has been compared in hypertensive and normotensive men. METHODS: The study was carried out in the community in Belfast and its environs. Thirty four men with mild to moderate hypertension aged 40-64 years were identified from general practice and a hypertension clinic. Normotensive men, matched for age and body mass index, were selected from a community survey. Subjects answered a sleep questionnaire and underwent overnight pulse oximetry at home. Computer analysis of the results gave the number and magnitude of dips in oxygen saturation (SaO2 dips, 4% or greater). RESULTS: The median number of SaO2 dips/hour for hypertensives was 2.0, and for normotensives was 0.8. Lowest SaO2 and mean SaO2 levels were significantly lower in the hypertensive group. Only one subject had a rate of SaO2 dips/hour greater than five and symptoms suggestive of OSA. CONCLUSIONS: Both hypertensive and normotensive men had relatively few episodes of nocturnal hypoxaemia. The small increase in the rate of SaO2 dips in hypertensive subjects has not yet been fully explained. These results imply that OSA is not common in hypertensive subjects and is unlikely to be an important cause of hypertension.

Humans↗
PubMed1993

MRI volumetric measurement of amygdala and hippocampus in temporal lobe epilepsy.

We performed MRI volumetric measurements of the amygdala (AM), the hippocampal formation (HF), and the anterior temporal lobe in a group of 30 patients with intractable temporal lobe epilepsy (TLE) and in seven patients with extratemporal lobe foci. Measurements were analyzed with a semiautomated software program and the results compared with those of normal controls and correlated with the findings of all other investigations. In particular, we compared the results with the lateralization of epileptic abnormalities in the EEG. Volumetric studies of AM and HF showed lateralization of measurable atrophy consistent with that derived from extracranial and intracranial EEG examinations. The HF volumes were more sensitive and provided a lateralization in 87%. Combined measurements of AM and HF showed lateralization in 93%, always congruent with the results of EEG lateralization. This slight but important additional improvement in discrimination justifies using AM measurements in MRI volumetric studies of mesial temporal structures. Volumetric studies combined with other currently employed noninvasive techniques may diminish the need for invasive methods of investigation in patients with TLE.

Adult↗
PubMed1993

Early childhood prolonged febrile convulsions, atrophy and sclerosis of mesial structures, and temporal lobe epilepsy: an MRI volumetric study.

We performed MRI volumetric measurements of the amygdala (AM) and hippocampal formation (HF) in a group of 43 patients with temporal lobe epilepsy not controlled by optimal drug treatment. Fifteen patients (35%) had a history of prolonged febrile convulsions (PFC) in early childhood; 30 patients underwent surgery, and histopathology was available in twenty-four. The mean values of AM and HF volumes ipsilateral to the EEG focus were significantly smaller than those of normal controls. The volumetric measurements showed a more pronounced atrophy of the AM in patients with a history of PFC, although the HF volumes were also smaller in this group. Patients with a history of PFC had a higher proportion of more severe mesial temporal sclerosis (MTS) compared with those with no PFC. These findings confirm a correlation between early childhood PFC, the severity of atrophy of mesial structures, and MTS.

Adolescent↗
PubMed1993

Simultaneous measurement of heart rate and body motion to quantitate physical activity.

None of the various methods used to measure habitual physical activity over days, weeks, or years in the general population have yet proven entirely satisfactory. A major problem is that no "gold standard" exists for the validation of various questionnaires, logs, or diaries that can be used in large sample population studies. Attempts have been made to accurately measure the activity profile by using heart rate or various motion sensors or accelerometers, but each approach has had significant limitations. The availability of new solid state recording techniques and computer-based analytic and display procedures now makes it possible to simultaneously record heart rate and body movement continuously for days and to combine the analysis of these data using customized software. Preliminary evaluation of this concept of simultaneous recording and analysis of heart rate and body motion via movement sensors on an arm and leg were conducted in 19 men. Subjects performed a variety of exercises in the laboratory during which heart rate, leg motion, arm motion, and oxygen uptake were recorded. Various issues regarding the prediction of energy expenditure from heart rate and body movement independently and in combination were evaluated. The results demonstrate that the accuracy of estimating oxygen uptake during a wide range of activities is improved when individualized heart rate--oxygen uptake regressions are used and heart rate and body movement are analyzed simultaneously rather that separately.

Adult↗
PubMed1993

Rejoinder.

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Catchment Area, Health↗
PubMed1992

Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction.

Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction contribute to the development of coronary heart disease. In a study comparing patients after myocardial infarction with controls, we have explored a possible association between coronary heart disease and a variation found in the gene encoding angiotensin-converting enzyme (ACE). The polymorphism ACE/ID is strongly associated with the level of circulating enzyme. This enzyme plays a key role in the production of angiotensin II and in the catabolism of bradykinin, two peptides involved in the modulation of vascular tone and in the proliferation of smooth muscle cells. Here we report that the DD genotype, which is associated with higher levels of circulating ACE than the ID and II genotypes, is significantly more frequent in patients with myocardial infarction (n = 610) than in controls (n = 733) (P = 0.007), especially among subjects with low body-mass index and low plasma levels of ApoB (P < 0.0001). The ACE/ID polymorphism seems to be a potent risk factor of coronary heart disease in subjects formerly considered to be at low risk according to common criteria.

Adult↗
PubMed1992

Viruses other than HIV and non-Hodgkin's lymphoma.

There are several viral infections which are known to cause lymphoma among animals; all establish latency in lymphoid cells. The human T-lymphotropic virus type I is a human virus which causes lymphomas among a subset of carriers. However, this virus is very restricted in its distribution and as such, is unlikely to play a role in the increase of non-Hodgkin's lymphoma (NHL). A highly prevalent infection, the Epstein-Barr virus (EBV) is known to play a role in the etiology of NHL among persons with acquired or inherited immune suppression. However, whether it is involved with "spontaneous" NHL is unknown. We have found evidence that among a group of 104 NHL patients with blood samples taken several years before diagnosis, there was an alteration in the antibody profile against the EBV which is quite similar to that seen for immune-suppressed patients prior to their diagnosis. This pattern is most evident in the oldest patients. This suggests that there may be an age-related subclinical immune suppression leading to chronic activation of EBV. If a viral infection is a major factor in the recent increase in NHL in the world, then we should consider the role of immune-suppressive exposures which have become widespread in recent decades.

Adult↗
PubMed1992

3-O-methyldopa administration does not alter fluorodopa transport into the brain.

To determine if 3-O-methyldopa (3OMD) significantly inhibits the transport of 6-[18F]fluorodopa (6-FD) into the brain at the concentration normally encountered during L-dopa administration, we performed 6-FD studies with positron emission tomography in cynomolgus monkeys in the presence and absence of 3OMD. Infusion of 3OMD was designed to produce plasma concentrations equivalent to those seen in patients on chronic L-dopa therapy. Plasma 3OMD levels of 39 +/- 4 microM did not alter the blood-brain transfer rate of 6-FD. 6-FD positron emission tomographic studies in parkinsonian patients will therefore not be altered by 3OMD present in the blood in those patients taking L-dopa preparations. These results do not support the hypothesis that transport of L-dopa into the brain is inhibited by 3OMD to cause the declining response seen in patients with advanced Parkinson's disease.

Amino Acid Transport Systems↗
PubMed1992

Steady-state visual evoked cortical potentials from stimulation of visual field quadrants. Optimizing pattern variables for the size of the field to be investigated.

The effects of check size and stimulus size were investigated to optimize the steady-state visual evoked cortical potentials from pattern-reversal stimulation of the visual field quadrants. Check sizes of 15', 30', 60', 90', 120' and 180' were investigated at a pattern reversal rate of 11.6 per second for field sizes varying from 2 degrees x 2 degrees to 24 degrees x 24 degrees. The visual evoked cortical potentials were recorded from mid occipital, right occipital and left occipital positions. In the inferonasal quadrant, the largest amplitudes were obtained with 30' and 60' check sizes; however, for these check sizes, the visual evoked cortical potential yielded limited additional information for field sizes greater than 4 degrees x 4 degrees and 6 degrees x 6 degrees, respectively. When a field size of 12 degrees x 12 degrees was investigated, a 90' check size was optimal. The results indicated that, with the above recording positions and check sizes of 15' to 120', there is an optimal number of pattern elements, 40 to 100, for stimulation of the inferonasal quadrant. This should be taken into account when a check size is selected to investigate a field quadrant of a particular size. Digital signal processing techniques were applied to analyze the visual evoked cortical potential, and the system shows promise for objective examination of the visual field.

Adult↗
PubMed1992

Comparison of dietary intakes in four selected European populations.

The composition of diet and food intakes in four selected European populations were compared. Dietary data (from the World Health Organization Project on Monitoring Trends and Determinants in Cardiovascular Disease) were measured by record methods and were available for middle-aged men in Finland (n = 653), France (n = 1128), Northern Ireland (n = 356), and southern Germany (Augsburg region; n = 899). Nutritional variables--which are independent of the absolute energy intake, such as the percentage supply of energy from macronutrients and the ratio of polyunsaturated to saturated fatty acids--were on the whole similar. However, striking differences were found in food intake and in the percentage supply of fat from different foods. The results indicate that detailed knowledge of consumption figures is necessary to develop prudent and acceptable nutrition intervention programs.

Adult↗
PubMed1992

The fascicular organisation of the cat optic nerve.

Mammalian optic nerve axons are organised within a fascicular framework. This pattern changes between the eye and the chiasm. For most of the length of the nerve fascicular patterns are apparent, but close to the chiasm, in a region of major fibre rearrangement, the fascicular configuration is lost. It is not known how this change occurs, or whether there are less obvious systematic changes in the number of fascicles or their geometry along the length of the nerve. In this study these questions have been addressed at successive locations along the length of the cat optic nerve. The number of fascicles varied depending upon the location examined. A relatively high number were found behind the eye. The number declined in the mid-orbital portion before increasing again in the region of the optic canal. Further caudally there was a progressive change in the pattern of fasciculation, with a loss of fascicular structure medially. The remaining fascicles became concentrated around the inferotemporal periphery of the nerve. There was no fascicular organisation at the point at which the two nerves fused at the chiasm. Although the number of fascicles varied along the length of the nerve their geometric pattern did not change.

Animals↗