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Biomedical subjects

M Conway

Publications and source records attributed to M Conway.

At least 19 recordsLinked to original sources

Electrical impedance tomography spectroscopy (EITS) for human head imaging.

Electrical impedance tomography (EIT) is a recently developed medical imaging method which has practical advantages for imaging brain function as it is inexpensive, rapid and portable. Its principal use in validated human studies to date has been to image changes in impedance at a single excitation frequency over time, but there are potential applications where it is desirable to obtain images from a single point in time, which could be achieved by imaging over multiple frequencies. We describe a novel multifrequency EIT design which provides up to 64 electrodes for imaging in the head. This was achieved by adding a multiplexer to a single channel of an existing system, the Sheffield Mark 3.5. This provides a flexible protocol for addressing up to 64 electrodes but CMRR decreases from 90 dB to 80 dB and analogue amplifier bandwidth from > 1.6 MHz to 0.8 MHz. This did not significantly affect performance, as cylinders of banana, 10% of the diameter of a saline filled spherical tank, could be visualized with frequency referenced imaging. The design appears to have been an acceptable compromise between practicality and performance and will now be employed in clinical trials of multifrequency EIT in stroke, epilepsy and neonatal brain injury.

Electric Impedance↗

Field-specific visual-evoked potentials: identifying field defects in vigabatrin-treated children.

OBJECTIVE: To derive a visual-evoked potential (VEP) technique for identifying visual field defects in children with epilepsy treated with vigabatrin and unable to perform perimetry. BACKGROUND: Studies have linked vigabatrin to a specific pattern of visual field loss. Few studies have included the pediatric population because of difficulties in assessing the visual field by perimetry below a developmental age of 9 years. METHODS: A field-specific VEP was developed with a central (0 degrees to 5 degrees radius) and peripheral stimulus (30 degrees to 60 degrees radius). Stimuli consisted of black and white checks that increased in size with eccentricity. Checks reversed at different rates, allowing separate central and peripheral responses to be recorded. Five vigabatrin-treated young adults with field defects were identified using this stimulus. Electroretinograms (ERG) were recorded to examine the effects of vigabatrin on retinal function. Thirty-nine children aged 3 to 15 years were included in the study. Twelve patients were examined by both the field-specific stimulus test and perimetry. The diagnostic performance of the field-specific stimulus test was compared with that of perimetry. RESULTS: Thirty-five of 39 children complied with the field-specific stimulus, 26 of 39 complied with the ERG, and 12 of 39 complied with perimetry. Using the summed amplitude of the peripheral response from O(2) and O(1), responses below 10 microV were deemed abnormal. The field-specific stimulus identified 3 of 4 abnormal perimetry results and 7 of 8 normal perimetry results, giving a sensitivity of 75% and a specificity of 87.5%. When comparing perimetry results with the ERG parameters, only the 30-Hz flicker amplitude, with a cutoff below 70 microV, gave a useful indication of visual field loss. CONCLUSION: Field-specific VEP are well tolerated by children older than 2 years of age and are sensitive and specific in identifying vigabatrin-associated peripheral field defects.

Anticonvulsants↗

Design and performance of the UCLH mark 1b 64 channel electrical impedance tomography (EIT) system, optimized for imaging brain function.

The UCLH Mark 1b is a portable EIT system that can address up to 64 electrodes, which has been designed for imaging brain function with scalp electrodes. It employs a single impedance-measuring circuit and multiplexer so that electrode combinations may be addressed flexibly using software. It operates in the relatively low frequency band between 225 Hz and 77 kHz, as lower frequencies produce larger changes during brain activity, and has a videocassette-sized headbox on a lead 10 m long, connected to a base box the size of a video recorder, and notebook PC, so that recordings may be made in ambulant subjects. Its performance was assessed using a resistor-capacitor network, and two saline-filled tanks-a cylindrical Perspex one and a latex one which contained a human skull. System signal-to-noise ratio was better than 50 dB and the maximum reciprocity error less than 10% for most frequencies. The CMMR was better than 80 dB at 38 kHz and a sponge, 20 mm across, which caused a local 12% impedance increase, was correctly localized in images. This suggests that the system has adequate performance to image impedance changes of 5-50% known to occur in the brain during normal activity, epilepsy or stroke; clinical trials to image these conditions are in progress.

Brain↗

Role of specific aminotransferases in de novo glutamate synthesis and redox shuttling in the retina.

In this study aminotransferase inhibitors were used to determine the relative importance of different aminotransferases in providing nitrogen for de novo glutamate synthesis in the retina. Aminooxyacetate, which inhibits all aminotransferases, blocked de novo glutamate synthesis from H(14)CO(3)(-) by more than 60%. Inhibition of neuronal cytosolic branched chain amino acid transamination by gabapentin or branched chain amino acid transport by the L-system substrate analog, 2-amino-bicyclo-(2,2,1)-heptane-2-carboxylic acid, lowered total de novo synthesis of glutamate by 30%, suggesting that branched chain amino acids may account for half of the glutamate nitrogen contributed by transamination reactions. L-cycloserine, an inhibitor of alanine aminotransferase, inhibited glutamate synthesis less than 15% when added in the presence of 5 mM pyruvate but 47% in the presence of 0.2 mM pyruvate. Although high levels of pyruvate blunted the inhibitory effectiveness of L-cycloserine, the results indicate that, under physiological conditions, alanine as well as branched chain amino acids are probably the predominant sources of glutamate nitrogen in ex vivo retinas. The L-cycloserine results were also used to evaluate activity of the malate/aspartate shuttle. In this shuttle, cytosolic aspartate (synthesized in mitochondria) generates cytosolic oxaloacetate that oxidizes cytosolic NADH via malate dehydrogenase. Because L-cycloserine inhibits cytosolic but not mitochondrial aspartate aminotransferase, L-cycloserine should prevent the utilization of aspartate but not its generation, thereby increasing levels of (14)C-aspartate. Instead, L-cycloserine caused a significant decline in (14)C-aspartate. The results suggest the possibility that shuttle activity is low in retinal Müller cells. Low malate/aspartate shuttle activity may be the molecular basis for the high rate of aerobic glycolysis in retinal Müller cells.

Acetates↗

Anger, negative emotions, and cardiovascular reactivity during interpersonal conflict in women.

OBJECTIVE: In order to evaluate the relationship between women's subjective emotional discomfort with anger and cardiovascular responses to stress, cardiovascular and affective responses were examined during two anger-provoking conditions: one in which anger would be in self-defense, and one in which anger would be in defense of a significant other. METHODS: A total of 42 healthy, normotensive women aged 18-35 years recruited a close female friend to participate in the study with them, and were randomly assigned to one of two harassment conditions: (i) Self-Harass, where women were harassed while performing a math task; (ii) Friend-Harass, where women witnessed a close female friend being harassed while their friend performed a math task. RESULTS: Self-Harass and Friend-Harass women reported feeling equally angry, annoyed, and irritated (all P's<.01) during their respective anger-provocation conditions. However, Self-Harass women reported experiencing significantly greater increases in feelings of depression and guilt during anger provocation (P's<.05) relative to Friend-Harass women. Interestingly, it was also the Self-Harass women who exhibited significantly greater elevations in heart rate (HR), cardiac output (CO), systolic blood pressure (SBP), forearm blood flow (FBF), and significant reductions in forearm vascular resistance (FVR; P's<.001) relative to Friend-Harass women during anger provocation. CONCLUSIONS: Results suggest that women may experience other negative emotions (e.g., guilt, depression) when anger is in self-defense relative to when it is in defense of others, and that these emotions may play a more important role than anger in moderating cardiovascular reactivity (CVR) during interpersonal conflict.

Adult↗

The structure of human mitochondrial branched-chain aminotransferase.

X-ray crystal structures of three forms of human mitochondrial branched-chain aminotransferase (BCAT) were solved by molecular-replacement methods, using Escherichia coli BCAT as the search model. The enzyme is a homodimer and the polypeptide chain of each monomer has two domains. The small domain is composed of residues 1--175 and the large domain is composed of residues 176--365. The active site is close to the dimer interface. The 4'-aldehyde of the PLP cofactor is covalently linked to the epsilon-amino group of the active-site lysine, Lys202, via a Schiff-base linkage in two of the structures. In the third structure, the enzyme is irreversibly inactivated by Tris. The overall fold of the dimer in human mitochondrial BCAT is similar to the structure of two bacterial enzymes, E. coli BCAT and D-amino acid aminotransferase (D-AAT). The residues lining the putative substrate-binding pocket of human BCAT and D-AAT are completely rearranged to allow catalysis with substrates of opposite stereochemistry. In the case of human mitochondrial branched-chain aminotransferase, a hydrogen-bond interaction between the guanidinium group of Arg143 in the first monomer with the side-chain hydroxyl of Tyr70 in the second monomer is important in the formation of the substrate-binding pocket.

Alanine Transaminase↗

What happens if you retest autobiographical memory 10 years on?

Burt (1992a, 1992b) reported data on the autobiographical memory of diarists for events that had occurred on average 3.3 years earlier. This paper reports data on 11 of the diarists, who were recontacted after a further 10 years and who agreed to a retest of their memory. Estimates of event date and event duration from the two recall attempts were compared. As predicted, duration estimation was extremely stable and showed no detrimental effects of the additional 10 years of retention interval. Estimation of event date was predicted to show an increase in forward telescoping due to the increased remoteness of the event sample, but, contrary to this prediction, backward telescoping dominated dating errors. A combination of the establishment of a recent boundary and Kemp's (1999) associative model of dating is proposed as an explanation for these results. It is argued that the nature of dating errors may depend on the time of the event's occurrence in the life span and the age of the individual dating the events.

Adult↗

Ordering autobiographical experiences.

This study examined individuals' memory for the temporal order of autobiographical events and for the components that constitute autobiographical events. Study 1 measured performance on an across-event ordering task that involved the chronological arrangement of cards that displayed event labels. Results indicated poor ordering ability across events, but a reasonable ability to order clusters of events. Study 2 compared within-event and across-event ordering using computer-presented digital photographs. Participants were better at ordering the photographs in their own across-event trials than in their within-event trials. The results are discussed in terms of the retrieval of temporal information under within- and across-event conditions.

Adolescent↗

On assessing individual differences in rumination on sadness.

The Rumination on Sadness Scale (RSS), an individual-difference measure of rumination on sadness, was developed as an alternative to the Ruminative Responses scale of the Response Styles Questionnaire (RRRSQ; Nolen-Hoeksema & Morrow, 1991). Research has shown the RRRSQ to consist of multiple, not highly intercorrelated factors; only I factor explicitly addresses rumination. In Study 1, a 1-factor solution to a principal components analysis was shown to hold for responses to the RSS. The RSS was also shown to be reliable. In Study 2, convergent and discriminant validity of the RSS were assessed. In Study 3, individuals with high RSS scores exhibited more distress regarding current concerns with the introduction of a delay period (to allow them to ruminate) after a sad mood induction.

Adolescent↗

Increased L-arginine transport in human erythrocytes in chronic heart failure.

1. Transport of L-arginine was investigated under zero-trans conditions in human erythrocytes from healthy donors and patients with heart failure. 2. Saturable influx of L-arginine was mediated by the classical cationic amino acid transport systems y+ and y+L. 3. The Vmax for L-arginine transport via system y+ increased from 292 to 490 mumol h-1 l-1 of cells in heart failure. 4. With system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), the Vmax for the transport of L-arginine via system y+L was unaffected in erythrocytes from patients with heart failure. 5. The inhibition of L-arginine and L-leucine influx by NG-monomethyl-L-arginine was similar in erythrocytes from control and heart failure patients. 6. Plasma L-arginine levels were reduced in patients with heart failure (59 mumol/l) compared with controls (125 mumol/l). Plasma from patients with heart failure also contained the endogenous L-arginine analogue NG-monomethyl-L-arginine, which was undetectable in plasma from controls. 7. Intracellular concentrations of L-arginine and NG-monomethyl-L-arginine were significantly elevated in erythrocytes from patients with heart failure compared with controls, consistent with an increased transport capacity for L-arginine and NG-monomethyl-L-arginine. 8. The present study provides the first evidence that system y+ mediates the increased transport of L-arginine in human erythrocytes from patients with chronic heart failure. These findings are similar to our previous results obtained in patients with chronic renal failure. Since both pathologies seem to present with an increased synthesis of nitric oxide, studies of L-arginine transport in erythrocytes may provide a valuable paradigm to study abnormalities of the L-arginine-nitric oxide signalling pathway.

Amino Acids↗

Corneal scarring and irregular astigmatism following refractive surgery in a corneal transplant.

BACKGROUND: Scarring may follow refractive surgery, causing irregular astigmatism and loss of visual acuity. METHODS: A case report of scarring and irregular astigmatism occurring in a corneal transplant following photorefractive keratectomy and arcuate incisions is presented. RESULTS: Following surgical excision of the scar, unaided visual acuity improved from 1/60 to 6/12. Histopathology of the excised scar was obtained. CONCLUSIONS: Refractive surgery following corneal transplantation may produce scarring. The origin of the scar in the present case has not been established.

Adult↗

Submacular surgery for subfoveal choroidal neovascular membranes in patients with presumed ocular histoplasmosis.

OBJECTIVE: To determine the visual results, recurrence rates, and postoperative complications of surgical removal of subfoveal choroidal neovascularization (CNV) in patients with the presumed ocular histoplasmosis syndrome. DESIGN: A consecutive surgical series of 63 eyes of 62 patients with subfoveal CNV and the presumed ocular histoplasmosis syndrome with longer than 6 months of follow-up. SETTING: Tertiary care university medical center. METHODS: Patients underwent surgical removal of subfoveal CNV using vitreoretinal surgical techniques. The anatomical and functional results of surgery were analyzed. RESULTS: The median age of the patients was 42 years (range, 16-68 years), and the median follow-up time was 24 months (range, 6-48 months). Visual acuity improved by 2 or more Snellen lines in 22 (35%) of the 63 eyes, was unchanged in 28 (44%) of the eyes, and worsened in 13 (21%) of the eyes. Eleven (17%) of the 63 eyes improved to a visual acuity of 20/50 or better. Eyes with an initial visual acuity of 20/200 or worse had a better prognosis for improved vision (ie, 26 [41%] of the eyes) than those with an initial visual acuity of 20/100 or better (ie, 5 [8%] of the eyes). Recurrence of the subfoveal CNV occurred in 24 (38%) of the 63 eyes and was more common in those eyes that received preoperative laser photocoagulation (ie, 15 [47%] of the eyes). The median time to recurrence was 5 months after surgery. Post-operative complications included macular striae in 4 (6%) of the 63 eyes, rhegmatogenous retinal detachment in 2 (3%) of the eyes, retinal tear in 1 (1.6%) of the eyes, and progression of cataract in 19 (30%) of the eyes. CONCLUSIONS: Surgical excision of subfoveal CNV may be an effective therapeutic modality in patients with the presumed ocular histoplasmosis syndrome that offers the possibility of improving central vision in many patients. Factors possibly associated with a favorable visual prognosis include younger patient age and the absence of previous laser photocoagulation.

Adolescent↗

Everyday activity parameters and competence in older adults.

Parameters of everyday activities in relation to cognitive, social, and emotional competence were examined in 2 studies. The parameters included frequency, difficulty, importance, intentions for future activities, changes in past activities, and ability of performance. The challenge hypothesis, in which performance of optional activities experienced as moderately difficult is associated with greatest well-being, was also tested. Two samples of older adults completed a life history interview and measures of psychological functioning. Parameters of activities necessary for maintaining an independent engaged lifestyle were measured by the Everyday Activities Questionnaire. In both studies, competence variables helped explain activity parameters independently of age and demographic variables. There was no support for the challenge hypothesis in either study.

Activities of Daily Living↗

Abnormal skeletal muscle bioenergetics in familial hypertrophic cardiomyopathy.

OBJECTIVE: To determine the skeletal muscle metabolic manifestations of familial hypertrophic cardiomyopathy. DESIGN: A case-control study. SETTING: 31P magnetic resonance spectroscopy of the calf muscle was performed on volunteers from a centre specialising in familial hypertrophic cardiomyopathy. PATIENTS: Five patients with abnormal beta myosin heavy chain protein in cardiac and skeletal muscle and five patients with a troponin T abnormality in cardiac muscle were compared with healthy controls. RESULTS: High energy phosphate metabolism in vivo was examined in a non-invasive manner. In resting muscle, the beta myosin heavy chain group had a higher ratio of phosphocreatine to ATP concentration (4.51 (SD 0.17)) than either the troponin T group (3.88 (0.42)) or controls (n = 16; 4.04 (0.40)). Exercise duration was reduced compared to controls, and during the fourth minute of exercise phosphocreatine depletion and muscle acidification were greater in both patient groups. After exercise, the recovery of phosphocreatine-an index of oxidative metabolic capacity of the muscle-was slower in the beta myosin heavy chain group (mean half time 0.65 (0.08) minutes) than in the troponin T group (0.60 (0.17) minutes) or controls (0.48 (0.14) minutes). CONCLUSIONS: Exercise metabolism was abnormal in both groups of subjects, and the affected contractile protein determined the metabolic changes in muscle at rest and during recovery. In patients with abnormal beta myosin heavy chain protein, there was a decrease in oxidative capacity consistent with the reduction in mitochondria reported in muscle biopsy studies of similar patients.

Adenosine Triphosphate↗

The impact of mood on information use in judgments of relationship satisfaction.

The hypothesis in Study 1 was that positive mood leads people to rely on both central and peripheral features of relationship quality when making global satisfaction judgments concerning their relationship with a spouse or partner, whereas sadness leads people to focus more exclusively on central features. For German university students, correlational analyses, within mood condition, of feature ratings with satisfaction judgments, both obtained following mood induction, revealed results consistent with the hypothesis. Study 2 again addressed the differential breadth of feature processing, by having a different group of German students categorize features of relationship quality after mood induction. As expected, participants in the positive mood condition used the fewest categories, whereas those in the neutral and sad mood conditions used the most categories.

Adult↗

Status, communality, and agency: implications for stereotypes of gender and other groups.

Four studies addressed the hypothesis, based on correspondence bias, that low- relative to high-status individuals are perceived as more communal and less agentic. Study 1 instantiated status in terms of occupations, and findings were as expected. The findings of Study 2 reconciled those of Study 1 and of A.H. Eagly and V.J. Steffen (1984) in that they demonstrated that high-status occupations are differentially construed in terms of their interpersonal communal demands. The hypothesis received clear support in Studies 3 and 4, in which a general instantiation of status independent of occupations, social roles, and gender was adopted. The findings are discussed in terms of gender stereotypes and social role theory of gender (A.H. Eagly, 1987) as well as in terms of other stereotypes.

Adolescent↗