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Biomedical subjects

A R Wright

Publications and source records attributed to A R Wright.

35 records · Page 2Linked to original sources

Cell swelling has differential effects on the rapid and slow components of delayed rectifier potassium current in guinea pig cardiac myocytes.

Cell swelling has been shown to cause activation of a variety of cardiac sarcolemmal ionic conductances including potassium channels. The aim of this study was to investigate the effect of swelling on the two subtypes of delayed rectifier potassium current (IKr and IKs) in single guinea pig myocytes using the whole-cell configuration of the patch clamp technique. When the holding potential was set at -40 mV and stepped to +40 mV for 1 s under isoosmotic conditions (300 mOsm) a delayed rectifier current (IK) was activated (0.86 +/- 0.05 nA; n = 43). Switching to a hypoosmotic solution (200 mOsm) caused a rapid increase in IK to a mean value of 1.43 +/- 0.10 nA (p < 0.05; n = 43). The effect of swelling on the two subtypes of IK was studied by analysis of deactivating tail currents using an envelope of tails protocol (stepping from -40 to +40 mV for 18 different pulse durations between 50 ms and 2.9 s; n = 16). Swelling caused a decrease in current amplitude measured at the end of the pulse (and IKtail) at short durations (< or = 150 ms) however, when the pulse duration was > 1 s swelling caused a significant increase in current. Using a pulse protocol to measure IKr with minimal contamination by IKs (voltage step from -40 to -10 mV for 250 ms) a 50-100 pA current was elicited which could be completely blocked by dofetilide (0.2 microM; n = 3). Introduction of hypoosmotic solution caused a significant decrease in IKr and when dofetilide (0.2 or 1.0 microM) was introduced the current remaining was decreased further (p < 0.05; n = 5), but was not completely blocked, thus suggesting that swelling had decreased the ability of dofetilide to block IKr. Similar results were obtained over a range of dofetilide concentrations and with a second IKr blocker, La3+. In Ca(2+)-free external solutions, pulsing to -10 mV for 500 ms to measure IKr in the absence of IKs, and to +60 mV for 5 s (with 0.2 microM dofetilide) to evoke only IKs, it was clear that swelling significantly increased IKs (pulse and tail currents) and decreased IKr. In addition, when measured using the perforated patch method, swelling modulated IKt and IKs in a similar fashion. We conclude that swelling has differential effects on the subtypes of the classical cardiac IK, which may have important implications in our understanding of the mechanisms underlying ischaemia- and reperfusion-induced arrhythmogenesis.

Animals↗

Hailey-Hailey disease maps to a 5 cM interval on chromosome 3q21-q24.

Hailey-Hailey disease (HHD) is a rare autosomal dominant genodermatosis characterized by disturbed keratinocyte adhesion. The disease has recently been mapped to a 14 cM region on chromosome 3q. We have further refined the location of the HHD gene by linkage analysis in six HHD families from Germany and Italy using 11 polymorphic microsatellite markers and found no evidence for genetic heterogeneity. We observed complete cosegregation between HHD and marker D3S1587, with a maximal lod score of 4.54. Detailed haplotype analyses allowed us to narrow the interval containing the HHD locus to 5 cM, flanked by D3S1589 and D3S1290.

Chromosome Mapping↗

Frank.

In medical school we are taught that the 'proper' relationship between doctor and patient is one where the doctor remains aloof and objective. Because of the nature of general practice we often form friendships with our patients. These friendships enrich our professional lives without detracting from the doctor-patient relationship.

Family Practice↗

20 hot job tracks.

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Data Collection↗

High resolution computed tomography of the lungs in patients with rheumatoid arthritis and interstitial lung disease.

We performed high resolution computed tomography (HRCT) on the lungs of 20 patients with RA and clinical and radiological evidence of interstitial lung disease (ILD). A case control group of patients with RA but without evidence of ILD were similarly studied and all patients underwent detailed pulmonary function testing. Clinical findings, drug therapy, smoking status, the presence/absence of SS and disease activity were also assessed. HRCT showed a range of abnormalities among patients thought to have ILD. Interstitial fibrosis was confirmed in 16 but was frequently associated with emphysema. Ground glass opacification was present in seven, while basal honey-combing was also evident in seven patients. Both these features were present in two patients with ILD. Bronchiectasis was identified in six patients and was the predominant finding in two patients previously thought to have ILD. Among the control patients, HRCT was normal in only five. Clinically unsuspected ILD was present in four patients, while a further four had bronchiectasis. Pleural disease was identified in seven controls. Pulmonary function tests were generally poor predictors of HRCT findings, although a reduced residual volume (RV) [> 1 S.D.] was 83% specific for the presence of ILD and a raised RV [> 1 S.D.] was 64% specific for emphysema. Smoking did not correlate with the presence of either ILD or emphysema and there were no correlations between disease activity and HRCT findings. RA patients with evidence of ILD have abnormalities on HRCT which cannot be confidently predicted on any other non-invasive test.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fine mapping of the Darier's disease locus on chromosome 12q.

Darier's disease (DD) is an autosomal dominant genodermatosis characterized by epidermal acantholysis and dyskeratosis. We have performed genetic linkage studies in 10 families with DD (34 affected) by analyzing 14 polymorphic microsatellite markers. Our results confirm recent reports mapping the DD gene to chromosome 12q23-q24.1. Haplotype analysis of recombinant chromosomes in our families, along with previously reported data, narrow the location of the DD gene to a 5 cM interval flanked by the loci D12S354 and D12S84/D12S105. This localization allowed exclusion of two known genes, PLA2A and PAH, as candidate loci for DD. Three other gene loci (PPP1C, PMCH, PMCA1), mapping in 12q21-q24, remain potential candidates.

Adolescent↗

Comparison of spiral-acquisition computed tomography and conventional computed tomography in the assessment of pulmonary metastatic disease.

In a prospective study, spiral-acquisition computed tomography (SACT) of the thorax was evaluated in 104 patients with extrathoracic malignancy and suspected pulmonary metastases, and was directly compared with conventional computed tomography (CCT) in 23 patients. The following parameters were assessed: lesion detectability; the effect on lesion detectability of reconstruction of scans at 5 mm and 10 mm slice increments; breathing artefact and slice misregistration. The radiation dose of the two techniques was measured using thermoluminescent dosimeters placed within an anthropomorphic chest phantom, and the visibility of simulated metastases inserted into the phantom was also compared using CCT, standard SACT and SACT with pitch greater than 1.0. Where metastases were present, SACT scans showed significantly better lesion detectability than CCT scans (p < 0.001). Image reconstruction of SACT data at 5 mm increments conferred no significant advantage in lesion detectability over 10 mm increment reconstructions. Compared with CCT, SACT scans showed reduced breathing artefact, and a complete absence of slice misregistration (p < 0.01). Phantom measurements of radiation dose and resolution were similar for both techniques. Increasing the pitch of the spiral in SACT caused only a small decrease in phantom resolution, but with the advantage of a reduction in the radiation dose. Spiral-acquisition CT is superior to conventional CT for the assessment of pulmonary metastatic disease.

Adolescent↗

Evaluation of "Gastromiro" for bowel opacification during computed tomography: comparison with diatrizoate and barium sulphate.

A new oral formulation of iopamidol, "Gastromiro", was evaluated as a bowel contrast agent during abdominal computed tomography (CT). Comparison was made with the well established agents sodium/meglumine diatrizoate ("Urografin 370") and dilute barium sulphate ("E-Z CAT") in a randomized, blind study of 150 consecutive patients undergoing abdominal and/or pelvic CT. Parameters assessed included quality of bowel opacification, artefact generation, contrast-medium palatibility, side effects and cost. No significant difference was found between the three contrast media in stomach- or small-bowel opacification. E-Z CAT was superior at opacifying the caecum/ascending colon. No compelling reason to choose a particular agent was found in the other assessed parameters, but cost is a significant factor.

Administration, Oral↗

Fat-suppression magnetic resonance imaging in the preoperative localization of parathyroid adenomas.

Prospective localization of parathyroid adenomas was attempted in 16 patients with hyperparathyroidism prior to surgery. All patients had magnetic resonance imaging (MRI) using T1-weighted spin-echo (SE) sequences and a fat-suppression sequence, the short-tau inversion recovery (STIR) sequence. Correlation with the results of surgery yielded an overall sensitivity of 71% and a specificity of 94%. Performance was good in patients with previous surgery and with ectopic tumours. We believe that fat-suppression MRI is a valuable technique in the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism.

Adenoma↗

MR pelvimetry--a practical alternative.

Pelvimetry remains a useful technique as part of the assessment of the term breech pregnancy where vaginal delivery is planned. MR pelvimetry is accurate, well tolerated and shows soft-tissue structures as well as bone. It avoids the potentially carcinogenic effects of ionising radiation and is thought to be completely safe for mother and fetus. A technique of MR pelvimetry is described which uses gradient-echo sequences. This quick, practical method makes minimal inroads into valuable scanning time, and may therefore be considered a potentially cost-effective alternative to conventional pelvimetry.

Adolescent↗

Effects of exercise on left ventricular diastolic performance in trained athletes.

Dynamically trained athletes develop increased left ventricular (LV) wall mass. To determine whether this increased wall mass impaired characteristics of LV diastolic filling, serial Doppler echocardiograms were obtained from 10 trained athletes (mean age 21 years) at rest, during supine graded bicycle exercise and during recovery at heart rates of 80, 120 and 140 beats/min, respectively. Similar studies were obtained in 10 age-matched control subjects. Studies at rest showed significant increases in athletes in LV end-diastolic dimension and indexed LV wall mass. Differences in peak filling rates and in normalized peak lengthening rates between athletes and control subjects were seen at heart rates of 140 beats/min during exercise and recovery. Differences in Doppler-derived variables between athletes and control subjects were seen in total time-velocity integral, early peak filling velocity and E/A ratio. In athletes, time-velocity integral was increased during recovery at heart rates of 120 beats/min and 80 beats/min, early peak filling velocity was increased during exercise at 120 beats/min and during recovery at 120 beats/min and 80 beats/min, and E/A ratio was higher at all heart rates during both exercise and recovery. Although no significant differences were found in LV diastolic filling indexes at rest, a significant enhancement was found in these parameters in dynamically trained athletes during exercise, particularly at higher levels of dynamic exercise.

Adult↗

A comparative study of left ventricular structure and function in elite athletes.

Adaptations to left ventricular (LV) structure and function appear to be dependent on the type, intensity and duration of exercise training. We therefore studied two clearly defined groups of elite athletes, by M-mode and Doppler echocardiography, with a group of inactive individuals as controls. All groups were age matched. Group 1 comprised ten elite endurance athletes with maximal oxygen consumption (VO2 max) of 74.7 +/- 1.43 (mean +/- SEM). Group 2 consisted of ten elite weightlifters with VO2 max 45.3 +/- 2.00. Group 3 comprised of ten inactive individuals with VO2 max 44.5 +/- 2.13. Left ventricular end diastolic dimension was significantly higher in group 1 (5.72 +/- 0.07) than in groups 2 or 3 (5.29 +/- 0.09 and 5.19 +/- 0.09 respectively, p less than 0.001). Left ventricular mass index was significantly higher in groups 1 and 2 (156.4 +/- 5.97 and 138.6 +/- 7.27 respectively) than in group 3 (104.1 +/- 3.16 p less than 0.001). Percentage fractional shortening was used as an index of systolic function and no significant difference was found between groups. Doppler E:A ratio was taken as an index of diastolic function and was found to be significantly elevated in group 1 at rest (3.37 +/- 0.24) compared with 2.38 +/- 0.16 and 1.99 +/- 0.10 in groups 2 and 3 respectively (p less than 0.003). On exercise, the E:A ratio in group 1 was significantly higher than in group 3 (1.95 +/- 0.14 and 1.23 +/- 0.05 respectively p less than 0.001), and tended to be higher than group 2 (1.68 +/- 0.15 p = ns). These data show that both modes of intense training produce left ventricular hypertrophy. Diastolic function is not impaired in the athletes and may be augmented in the endurance athletes.

Adolescent↗

Computed tomography in the preoperative assessment of Poland's syndrome.

Four cases of Poland's syndrome were investigated with thoracic computed tomography (CT) to determine the precise extent of the upper limb girdle abnormalities. CT confirmed in all cases the absence of the sternocostal head of pectoralis major and clearly showed associated abnormalities of pectoralis minor, serratus anterior and latissimus dorsi as well as bony structures. In view of the importance of latissimus dorsi in reconstructive surgery, we believe that a limited thoracic CT scan provides useful information in patients with Poland's syndrome requesting anterior axillary reconstruction and breast mound formation.

Adolescent↗

MR and CT in the assessment of Poland syndrome.

Seven cases of Poland syndrome were investigated with CT and/or MR to assess the extent of the muscle abnormalities of the shoulder girdle. In all cases the absence of the sternocostal head of the pectoralis major was clearly shown, as were any associated abnormalities of the pectoralis minor, serratus anterior, and latissimus dorsi. The latissimus dorsi muscle has an important role in reconstructive surgery and can be difficult to assess clinically. Cross-sectional imaging with CT or MR will give useful information in patients with Poland syndrome requesting anterior axillary reconstruction and breast mound formation.

Adolescent↗