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Biomedical subjects

N Roberts

Publications and source records attributed to N Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2002

Psychological well-being in patients on 'adequate' doses of l-thyroxine: results of a large, controlled community-based questionnaire study.

OBJECTIVE: Over 1% of the UK population is receiving thyroid hormone replacement with l-thyroxine (T4). However, many patients complain of persistent lethargy and related symptoms on T4 even with normal TSH levels. To date there has been no large study to determine whether this is related to thyroxine replacement or coincidental psychological morbidity. We have therefore attempted to address this issue using a large, community-based study. DESIGN AND PATIENTS: Computerized prescribing records of five general practices were used to identify 961 patients who had been on thyroxine for a minimum of 4 months from a population of 63 000 (1.5%), along with age- and sex-matched controls. All 1922 individuals were sent a two-page questionnaire, made up of the short form of the General Health Questionnaire (GHQ-12), designed to detect minor psychiatric disorders in the community, and a 12-question 'thyroid symptom questionnaire' (TSQ) in the same format. A covering letter explained that we were interested in 'how patients felt on medication' and made no direct reference to thyroxine. MEASUREMENTS: Scores from the GHQ and TSQ were marked for each individual using the GHQ and Likert scoring methods. Patients' latest TSH measurements were obtained from laboratory records. Comparisons were then made on scores for the total GHQ-12, TSQ and individual questions between patients (P) and control (C) groups. Separate analyses were made comparing the patients with a normal TSH (nP) and the control group. RESULTS: Five hundred and ninety-seven (62%) of the patients (P) and 551 (57%) of the controls (C) responded and fully completed at least one of the two questionnaire. Three hundred and ninety-seven responding patients (nP) had a TSH estimation performed in the previous 12 months with the last result being in the local laboratory normal range for TSH (0.1-5.5 or 0.2-6.0 mU/l, according to the assay method used). The responding P, nP and C populations were well matched for age (59.96, 59.73, 59.35 years) and sex (85%, 83%, 87% female). The number of individuals scoring 3 or more on the GHQ-12 (indicating 'caseness') was 21% higher in P than C [185/572 (32.3%) vs. 137/535 (25.6%), P = 0.014] and 26% higher in nP than C [131/381 (34.4%) vs. 137/535 (25.6%), P < 0.005]. Stronger differences were seen with the TSQ scores [C = 187/535 (35.0%), P = 273/583 (46.8%), P < 0.001, P vs. C; and nP = 189/381 (48.6%), P < 0.001, nP vs. C]. Differences existed in chronic drug use and chronic disease prevalence between the control and patient groups, but the differences in GHQ and TSQ scores between the groups remained significant even after correction for these factors as well as age and sex in multiple regression analysis. CONCLUSIONS: This community-based study is the first evidence to indicate that patients on thyroxine replacement even with a normal TSH display significant impairment in psychological well-being compared to controls of similar age and sex. In view of the large numbers of people on thyroxine replacement, we believe that these differences, although not large, could contribute to significant psychological morbidity in a substantial number of individuals.

Adolescent↗
PubMed2002

Candida davenportii sp. nov., a potential soft-drinks spoilage yeast isolated from a wasp.

During a survey of yeast ecology in a soft-drinks production facility, a dead wasp was removed from the sampling tap of an external sugar-syrup storage tank. A yeast isolated from the dead wasp was found to be similar, although not identical, in its physiological characteristics to Candida lactis-condensi and Candida stellata. Sequence analysis of the 26S rDNA D1/D2 variable domain revealed that this isolate was most closely related to C stellata, but differed sufficiently in its D1/D2 sequence to indicate that it belonged to a separate species. The yeast species has been named Candida davenportii sp. nov.; the type strain is NCYC 3013T (= CBS 9069T). C davenportii sp. nov. was osmotolerant, moderately preservative-resistant and able to grow in very acidic conditions, i.e. pH 14. This yeast grew well in fruit-containing soft drinks, cola-type beverages and a synthetic soft drink and is therefore a potential cause of spoilage of soft drinks and other sugary food products. Other related yeast species in the same taxonomic clade as C davenportii sp. nov. are also osmotolerant, growing in < 50% (w/v) sugar. Many of these species are associated with insects, specifically bees, bumblebees and leafcutter bees, and many have been reported as the causative agent of spoilage of sugary foods, such as condensed milk, fruit juices and concentrates. It is proposed that C davenportii sp. nov. and other closely related yeasts are primarily associated with Aculeates (bees and wasps). In turn, bees and wasps are attracted by sugary residues in foods such as fruit juices and concentrates, forming the source of infection of these yeasts and thus instigating spoilage.

Animals↗
PubMed2002

Voxel based morphometry of grey matter abnormalities in patients with medically intractable temporal lobe epilepsy: effects of side of seizure onset and epilepsy duration.

OBJECTIVES: To investigate the use of whole brain voxel based morphometry (VBM) and stereological analysis to study brain morphology in patients with medically intractable temporal lobe epilepsy; and to determine the relation between side, duration, and age of onset of temporal lobe epilepsy, history of childhood febrile convulsions, and grey matter structure. METHODS: Three dimensional magnetic resonance images were obtained from 58 patients with left sided seizure onset (LSSO) and 58 patients with right sided seizure onset (RSSO), defined using EEG and foramen ovale recordings in the course of presurgical evaluation for temporal lobectomy. Fifty eight normal controls formed a comparison group. VBM was used to characterise whole brain grey matter concentration, while the Cavalieri method of modern design stereology in conjunction with point counting was used to estimate hippocampal and amygdala volume. Age and sex were used as confounding covariates in analyses. RESULTS: LSSO and RSSO patients showed significant reductions in volume (using stereology) and grey matter concentration (using VBM) of the hippocampus, but not of the amygdala, in the presumed epileptogenic zone when compared with controls, but hippocampal (and amygdala) volume and grey matter concentration were not related to duration or age of onset of epilepsy. LSSO and RSSO patients with a history of childhood febrile convulsions had reduced hippocampal volumes in the presumed epileptogenic zone compared with patients without such a history. Left amygdala volume was also reduced in LSSO patients with a history of childhood convulsions. VBM results indicated bilateral thalamic, prefrontal, and cerebellar GMC reduction in patients, which correlated with duration and age of onset of epilepsy. CONCLUSIONS: Hippocampal sclerosis is not necessarily the consequence of recurrent temporal lobe seizures. A major cause of hippocampal sclerosis appears to be an early aberrant neurological insult, such as childhood febrile seizures. Secondary brain abnormalities exist in regions outside the presumed epileptogenic zone and may result from recurrent seizures.

Adolescent↗
PubMed2001

Theories of episodic memory.

Theories of episodic memory need to specify the encoding (representing), storage, and retrieval processes that underlie this form of memory and indicate the brain regions that mediate these processes and how they do so. Representation and re-representation (retrieval) of the spatiotemporally linked series of scenes, which constitute an episode, are probably mediated primarily by those parts of the posterior neocortex that process perceptual and semantic information. However, some role of the frontal neocortex and medial temporal lobes in representing aspects of context and high-level visual object information at encoding and retrieval cannot currently be excluded. Nevertheless, it is widely believed that the frontal neocortex is mainly involved in coordinating episodic encoding and retrieval and that the medial temporal lobes store aspects of episodic information. Establishing where storage is located is very difficult and disagreement remains about the role of the posterior neocortex in episodic memory storage. One view is that this region stores all aspects of episodic memory ab initio for as long as memory lasts. This is compatible with evidence that the amygdala, basal forebrain, and midbrain modulate neocortical storage. Another view is that the posterior neocortex only gradually develops the ability to store some aspects of episodic information as a function of rehearsal over time and that this information is initially stored by the medial temporal lobes. A third view is that the posterior neocortex never stores these aspects of episodic information because the medial temporal lobes store them for as long as memory lasts in an increasingly redundant fashion. The last two views both postulate that the medial temporal lobes initially store contextual markers that serve to cohere featural information stored in the neocortex. Lesion and functional neuroimaging evidence still does not clearly distinguish between these views. Whether the feeling that an episodic memory is familiar depends on retrieving an association between a retrieved episode and this feeling, or by an attribution triggered by a priming process, is unclear. Evidence about whether the hippocampus and medial temporal lobe cortices play different roles in episodic memory is conflicting. Identifying similarities and differences between episodic memory and both semantic memory and priming will require careful componential analysis of episodic memory.

Brain↗
PubMed2001

An fMRI study of stimulus equivalence.

In order to study brain activation during the formation of equivalence relations, 12 subjects underwent fMRI during matching-to-sample (MTS) tests of (1) previously trained arbitrary relationships between iconic stimuli and the untrained, emergent relations of (2) symmetry, (3) transitivity, and (4) symmetry with transitivity, plus a test of verbal fluency (VF). Brain activation was similar in all MTS tasks and in the VF task. In particular, both types of task activated dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex bilaterally. However VF, but not the MTS tasks, activated Broca's area. In three of the four MTS tasks, behavioural accuracy was significantly correlated with left lateralisation of DLPFC activity. Brain activation patterns during equivalence thus resembled those involved in semantic processing underlying language, without involving regions concerned with the simple sub-vocal articulation of stimulus names.

Adult↗
PubMed2001

Effect of preslaughter feed withdrawal period on longissimus tenderness and the expression of calpains in the ovine.

The objective was to study the role of calpains in meat tenderness. Lambs were fasted for various periods of time to generate differences in meat tenderness and to determine in tandem the expression of calpain 1, calpain 2, calpain 3, and calpastatin. The assumption has been that increased calpain expression associated with an increase in tenderness indicates a role for calpain in the tenderization process and vice versa. Fasting lambs for 1 day caused a significant improvement in longissimus (LD) tenderness compared to the control. Correlations between the tenderness of the LD and the expression of the calpains and calpastatin were significant for calpains 1 and 3 but not for calpain 2 or calpastatin. Consequently, this study supports a role for calpains 1 and 3, but not for calpain 2, in the tenderization of the LD from fasted lambs during post-mortem aging.

Animals↗
PubMed2001

Melatonin in plant organs.

The indoleamine melatonin, a well-known animal chemical, has been identified in extracts from several plant species. The function of melatonin in plants is unknown. Two major functions of melatonin in animals are dark signaling and antioxidant protection. Fruit ripening was used as a model physiological process that involves changes in the oxidative status of an organ. Tomato fruits at various stages of ripeness were sampled. Morning glory (Pharbitis nil Choisy, cv. Violet) and tomato (Lycopersicon esculentum Mill., cv. T5 and Castlemart) organs were collected throughout a light/dark cycle to determine whether melatonin levels increased during the night. No consistent evidence was found that melatonin increased significantly in organs of these plants during the night, as it does in many animals. The melatonin content of the fruits generally increased during ripening up to the mature ripe stage and thereafter as the fruit became over ripe.

Animals↗
PubMed2001

Mitochondrial function and oxygen supply in normal and in chronically ischemic muscle: a combined 31P magnetic resonance spectroscopy and near infrared spectroscopy study in vivo.

PURPOSE: We used (31)P magnetic resonance spectroscopy (MRS) and near-infrared spectroscopy (NIRS) as a means of quantifying abnormalities in calf muscle oxygenation and adenosine triphosphate (ATP) turnover in peripheral vascular disease (PVD). METHODS: Eleven male patients with PVD (mean age, 65 years; range, 55-76 years) and nine male control subjects of similar age were observed in a case-control study in vascular outpatients. Inclusion criteria were more than 6 months' calf claudication (median, 1.5 years; range, 0.6-18 years); proven femoropopliteal or iliofemoral occlusive or stenotic disease; maximum treadmill walking distance (2 km/h, 10 degrees gradient) of 50 to 230 m (mean, 112 m); ankle-brachial pressure index of 0.8 or less during exercise (mean, 0.47; range, 0.29-0.60). Exclusion criteria included diabetes mellitus, anemia, and magnet contraindications. Simultaneous (31)P MRS and NIRS of lateral gastrocnemius was conducted during 2 to 4 minutes of voluntary 0.5 Hz isometric plantarflexion at 50% and 75% maximum voluntary contraction force (MVC), followed by 5 minutes recovery. Each subject was studied three times, and the results were combined. RESULTS: Compared with control subjects, patients with PVD showed (1) normal muscle cross-sectional area, MVC, ATP turnover, and contractile efficiency (ATP turnover per force/area); (2) larger phosphocreatine (PCr) changes during exercise (ie, increased shortfall of oxidative ATP synthesis) and slower PCr recovery (47% +/- 7% [mean +/- SEM] decrease in functional capacity for oxidative ATP synthesis, P = .001); (3) faster deoxygenation during exercise and slower postexercise reoxygenation (59% +/- 7% decrease in rate constant, P = .0009), despite reduced oxidative ATP synthesis; (4) correlation between PCr and NIRS recovery rate constants (P < .02); and (5) correlations between smaller walking distance, slower PCr recovery, and reduced MVC (P < .001). The precision of the key measurements (rate constants and contractile efficiency) was 12% to 18% interstudy and 30% to 40% intersubject. CONCLUSION: The primary lesion in oxygen supply dominates muscle metabolism. Reduced force-generation in patients who are affected more may protect muscle from metabolic stress.

Adenosine Triphosphate↗
PubMed2001

A proton magnetic resonance spectroscopy study of age-related changes in frontal lobe metabolite concentrations.

Ageing is associated with reduction of grey matter volume and it is reported that the frontal lobes are preferentially affected. We have applied quantitative magnetic resonance spectroscopy (MRS), incorporating measurement of brain tissue water content and metabolite T(2) relaxation times, to determine absolute concentrations of the putative neuronal marker N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) compounds in the frontal lobe of 50 male subjects aged between 20 and 70 years (10 per decade). The fractional brain water content (beta(MR)) did not change significantly as a function of age (r = 0.07, P = 0.65) and had a mean value of 81% (CV = 2%). The concentration (in millimoles per litre brain tissue) of NAA decreased significantly with age (r = -0.42, P = 0.003), with an overall decrease of 12% between the third and seventh decades. The concentrations of Cr and Cho did not change significantly with age. The interpretation of the age-dependent decrease in NAA concentration as reflecting either a reduction in neuronal volume, number or function is discussed.

Adult↗
PubMed2000

Failure of cidofovir therapy in progressive multifocal leukoencephalopathy unrelated to human immunodeficiency virus.

We describe the first reported human immunodeficiency virus (HIV)-seronegative patient treated with cidofovir for progressive multifocal leukoencephalopathy (PML). Marked clinical and radiological progression of PML occurred during cidofovir therapy. The improvement observed during cidofovir therapy of HIV-infected patients may be due to the effect of concomitant antiretroviral therapy rather than cidofovir.

Anti-HIV Agents↗
PubMed2000

Convergent neuroanatomical and behavioural evidence of an amygdala hypothesis of autism.

In this study we report a convergence of behavioural and neuroanatomical evidence in support of an amygdala hypothesis of autism. We find that people with high-functioning autism (HFA) show neuropsychological profiles characteristic of the effects of amygdala damage, in particular selective impairment in the recognition of facial expressions of fear, perception of eye-gaze direction, and recognition memory for faces. Using quantitative magnetic resonance (MR) image analysis techniques, we find that the same individuals also show abnormalities of medial temporal lobe (MTL) brain structure, notably bilaterally enlarged amygdala volumes. These results combine to suggest that developmental malformation of the amygdala may underlie the social-cognitive impairments characteristic of HFA. This malformation may reflect incomplete neuronal pruning in early development.

Adolescent↗
PubMed2000

Quantitative analysis of gene amplification in insecticide-resistant Culex mosquitoes.

The amplification of carboxylesterase structural genes followed by their overexpression is the most common mechanism of resistance to organophosphorus insecticides in Culex mosquitoes. Most resistant Culex quinquefasciatus mosquitoes have co-amplified estalpha2(1) and estbeta2(1) genes. Recently, Southern, DNA dot-blot analysis and phosphorimaging technology were used to quantify the est gene copy number in aphids and mosquitoes. Although more accurate than autoradiography, this method relies on probe hybridization, which can be variable. We have directly measured gene and mRNA copy number by using real-time quantitative PCRs in mosquitoes. The acquisition of fluorescence from incorporation of the double-strand-specific dye SYBR GreenI into a PCR product once per cycle is used to provide an absolute quantification of the initial template copy number. Thus it has been possible to show that estalpha2(1) and estbeta2(1) are co-amplified approx. 80-fold in the genome of the resistant PelRR strain of C. quinquefasciatus. The two genes, although co-amplified in a 1:1 ratio, are differentially transcribed: the estbeta2(1) gene from this amplicon has greater transcription than estalpha2(1) in all individual mosquito larvae tested, with an average ratio of 10:1. Purified esterases from mosquito homogenates were found in a ratio of 3:1, which, combined with the quantitative mRNA data, suggests the operation of both transcriptional and translational control mechanisms to regulate the expression of the amplified genes in C. quinquefasciatus insecticide-resistant mosquitoes.

Animals↗
PubMed2000

Postprandial decrease in splenic volume demonstrated by magnetic resonance imaging and stereology.

The aim of this study was to determine if the volume of the spleen changes after food intake. We applied an unbiased and efficient method for splenic volume estimation using magnetic resonance imaging (MRI) in combination with modern design stereology. MR images of the spleen were obtained for 10 healthy volunteers (five men and five women; mean age 28.9 years [range 23-35 years]) without a history of splenomegaly. The initial scans were performed in the morning after overnight fasting. Each volunteer then consumed a standard balanced meal weighing 500 g [2,460 kJ (627 kcal) energy] with 500 ml of still mineral water. Second identical MR scans were performed approximately 1 hr later. Postprandially, splenic volume decreased by an average of 6.6% (P = 0.005), probably due to increased splanchnic blood flow after food intake.

Adult↗
PubMed2000

Estimation of body composition in muscular dystrophy by MRI and stereology.

We have applied the Cavalieri method of modern design stereology with magnetic resonance imaging for estimating the volume of whole-body muscle and fat compartments in four patients with muscular dystrophy, a patient with myopathy, five controls, an anorexic subject, and a body builder. Detailed systematic series (ie, 50) of axial MR images (T1-weighted, TR/TE 400/10 msec) were obtained throughout the whole body of each subject. The results showed that 15, 20, and 35 axial sections through the body are sufficient to secure coefficients of error (CEs) on the estimates of total muscle and fat volume of around 10%, 5%, and 3% respectively in muscular dystrophy patients and controls. The mean normalized volumes of muscle in four muscular dystrophy patients were decreased by 27% (t-test: P < 0.05), and those of total fat were increased by 12% (t-test: P > 0.05) relative to controls. The Cavalieri method provides a direct, efficient, and mathematically unbiased approach for studying human body compartments and may have application in assessing treatment efficacy in patients with muscular dystrophy. J. Magn. Reson. Imaging 2000;12:467-475.

Adipose Tissue↗
PubMed2000

A comparison of egocentric and allocentric spatial memory in a patient with selective hippocampal damage.

The spatial memory of a single patient (YR) was investigated. This patient, who had relatively selective bilateral hippocampal damage, showed the pattern of impaired recall but preserved item recognition on standardised memory tests that has been suggested by Aggleton and Shaw [Aggleton JP, Shaw C. Amnesia and recognition memory: a reanalysis of psychometric data. Neuropsychologia 1996;34:51-62] to be a consequence of Papez circuit lesions. YR was tested on three recall tests and one recognition test for visuospatial information. The initial recall test assessed visuospatial memory over very short unfilled delays and YR was not significantly impaired. This test was then modified to test recall of allocentric and egocentric spatial information separately after filled delays of between 5 and 60 s. YR was found to be more impaired at recalling allocentric than egocentric information after a 60 s interval with a tendency for the impairment to increase up to this delay. Recognition of allocentric spatial information was also assessed after delays of 5 and 60 s. YR was impaired after the 60 s delay. The results suggest that the human hippocampus has a greater involvement in allocentric than egocentric spatial memory, and that this most likely concerns the consolidation of allocentric information into long-term memory rather than the initial encoding of allocentric spatial information. The findings also suggest that YR's item recognition/free recall deficit pattern reflects a problem retrieving or storing certain kinds of associative information.

Brain Mapping↗
PubMed2000

The neuraminidase inhibitor GS4104 (oseltamivir phosphate) is efficacious against A/Hong Kong/156/97 (H5N1) and A/Hong Kong/1074/99 (H9N2) influenza viruses.

In 1997, an H5N1 avian influenza A/Hong Kong/156/97 virus transmitted directly to humans and killed six of the 18 people infected. In 1999, another avian A/Hong/1074/99 (H9N2) virus caused influenza in two children. In such cases in which vaccines are unavailable, antiviral drugs are crucial for prophylaxis and therapy. Here we demonstrate the efficacy of the neuraminidase inhibitor GS4104 (oseltamivir phosphate) against these H5N1 and H9N2 viruses. GS4071 (the active metabolite of oseltamivir) inhibited viral replication in MDCK cells (EC(50) values, 7.5-12 microM) and neuraminidase activity (IC(50) values, 7.0-15 nM). When orally administered at doses of 1 and 10 mg/kg per day, GS4104 prevented death of mice infected with A/Hong Kong/156/97 (H5N1), mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2), or human A/Hong Kong/1074/99 (H9N2) viruses and reduced virus titers in the lungs and prevented the spread of virus to the brain of mice infected with A/Hong Kong/156/97 (H5N1) and mouse-adapted A/Quail/Hong Kong/G1/97 (H9N2) viruses. When therapy was delayed until 36 h after exposure to the H5N1 virus, GS4104 was still effective and significantly increased the number of survivors as compared with control. Oral administration of GS4104 (0.1 mg/kg per day) in combination with rimantadine (1 mg/kg per day) reduced the number of deaths of mice infected with 100 MLD(50) of H9N2 virus and prevented the deaths of mice infected with 5 MLD(50) of virus. Thus, GS4104 is efficacious in treating infections caused by H5N1 and H9N2 influenza viruses in mice.

Acetamides↗
PubMed2000

Quantitative magnetic resonance imaging in consecutive patients evaluated for surgical treatment of temporal lobe epilepsy.

We present the results of quantitative Magnetic Resonance Imaging (MRI) in 55 consecutively referred patients with clinical evidence of temporal lobe epilepsy (TLE). The Cavalieri method was used in combination with point counting to provide unbiased estimates of the volume of the left and right hippocampus, amygdala, temporal lobe, lateral ventricles and cerebral hemisphere, and pixel by pixel maps of the T2 relaxation time were computed for both central and anterior sections of the hippocampus. The 99th centiles of hippocampal volume, hippocampal volume asymmetry and T2 relaxation times in 20 control subjects provided limits which identified the presence of MTS. The results of the quantitative MRI were compared with the results of conventional diagnostic MRI, foramen ovale (FO) recording and the WADA test. Thirty-one patients were found to have unilateral MTS (17 left and 14 right) and 7 bilateral MTS. No evidence of MTS was detected in 16 patients. Of the 31 patients diagnosed with unilateral MTS on the basis of hippocampal volume and T2 measurement, 74% and 77% would respectively have received the same diagnosis on the basis of hippocampal volume and T2 measurements alone. In comparison to FO recording, quantitative MRI has a sensitivity of 55% and a specificity of 86%, while conventional diagnostic MRI has a sensitivity of 42% and a specificity of 80% for detection of MTS. Unilateral abnormalities were detected by FO recording in 30% cent of patients who appeared normal on quantitative MRI. WADA test results were available for 40 patients. The findings were consistent with quantitative MRI showing reduced memory function ipsilateral to unilateral MTS in 18 patients, but reduced memory function contralateral to unilateral MTS in two patients, and reduced memory function without MR abnormality in seven patients. WADA testing revealed unilateral memory impairments where MRI found bilateral pathology in 4 patients and in 4 patients in whom quantitative MRI detected unilateral MTS there was no evidence of reduced memory during WADA testing of the corresponding cerebral hemisphere. In the patients with unilateral right MTS a highly significant negative correlation (p = 0.0003) was observed between age of onset and the volume of the contralateral temporal lobe. Quantitative MR imaging of the hippocampus (i.e. volume and T2 measurement) is preferable to conventional radiological reporting for providing objective evidence of the presence of MTS on which to base the referral of patients for surgery, and since it has associated morbidity FO recording is now only being used in selected patients. Furthermore, stereology provides a convenient method for estimating the volume of other brain structures, which is relevant to obtaining a better understanding of the effects of laterality and age of onset of TLE.

Adolescent↗