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Biomedical subjects

A Watson

Publications and source records attributed to A Watson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Automated sample introduction for an imaged capillary isoelectric focusing instrument via high-performance liquid chromatography sampling devices.

Sample introduction of an imaged capillary isoelectric focusing (cIEF) instrument is fully automated by using commercially available high-performance liquid chromatography (HPLC) injection valves and autosamplers. Sample carryover can be controlled to under 1% when the valve and separation column are washed for 1 min between sample runs. The standard deviation of peak areas for 20 injections is 3.5%, which includes deviations created by the absorption imaging detector and the isoelectric focusing process inside the 75 microm I.D. column. Sample throughput is up to 10 samples per hour. The instrument has been applied to fast analysis of many proteins including monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1998

Optimizing separation conditions for proteins and peptides using imaged capillary isoelectric focusing.

Separation conditions for antibodies, glycoproteins and peptides were optimized to fully realize the potential of automated imaged capillary isoelectric focusing (imaged cIEF) for protein analysis. Two commercially available capillary coatings, polyacrylamide and fluorocarbon, were found to provide reproducible results for cIEF separations. Both coatings could last more than 100 runs under normal cIEF conditions. Up to 30 mM salts (Na+) could be added to samples to prevent protein precipitation before and during isoelectric focusing performed under imaged cIEF. Short analysis time of the imaged cIEF also aided in the prevention of protein precipitation. High current at the beginning of the focusing for samples in salt could be avoided by applying a voltage gradient. Additions of up to 6 M urea and 20% glycerol could enhance solubility of proteins and peptide. Imaged cIEF was applied to the quantitation of monoclonal antibodies.

Automation↗
PubMed1998

Phosphorylation of c-Jun is necessary for apoptosis induced by survival signal withdrawal in cerebellar granule neurons.

Cerebellar granule neurons die by apoptosis when deprived of survival signals. This death can be blocked by inhibitors of transcription or protein synthesis, suggesting that new gene expression is required. Here we show that c-jun mRNA and protein levels increase rapidly after survival signal withdrawal and that transfection of the neurons with an expression vector for a c-Jun dominant negative mutant protects them against apoptosis. Phosphorylation of serines 63 and 73 in the c-Jun transactivation domain is known to increase c-Jun activity. By using an antibody specific for c-Jun phosphorylated on serine 63, we show that this site is phosphorylated soon after survival signal withdrawal. To determine whether c-Jun phosphorylation is necessary for apoptosis, we have expressed c-Jun phosphorylation site mutants in granule neurons. c-Junasp, a constitutively active c-Jun mutant in which the known and potential serine and threonine phosphoacceptor sites in the transactivation domain have been mutated to aspartic acid, induces apoptosis under all conditions tested. In contrast, c-Junala, which cannot be phosphorylated because the same sites have been mutated to alanine, blocks apoptosis caused by survival signal withdrawal. Finally, we show that cerebellar granule neurons contain high levels of Jun kinase activity and low levels of p38 kinase activity, neither of which increases after survival signal withdrawal. Mitogen-activated protein kinase activity decreases under the same conditions. These results suggest that c-Jun levels and c-Jun phosphorylation may be regulated by novel mechanisms in cerebellar granule neurons.

Animals↗
PubMed1998

Technology for microarray analysis of gene expression.

The past year has demonstrated the versatility of microarrays for the analysis of whole model-organism genomes and has seen the development of chips to measure the expression of 40,000 human genes. Microarray technology has also become considerably more robust and sensitive. Technology enhancements include the use of noncontact printing methods, improved 2-color sample preparation, and statistically based software for data analysis.

Biotechnology↗
PubMed1998

Measurement of axial length in the calculation of intraocular lens power.

PURPOSE: Accurate measurement of ocular axial length is essential for accurate intraocular lens (IOL) power calculation. Although it is common practice to average several axial length measurements to improve accuracy, it has been suggested that a single high-quality A-scan ultrasonographic measurement is adequately accurate owing to the high test-retest reliability of A-scan biometry. The aim of this study was to compare the accuracy of a single high-quality A-scan measurement with that of the average of three acceptable measurements in the calculation of IOL power. METHOD: We studied 103 eyes of 103 patients who underwent cataract-IOL surgery. All these patients underwent pre-operative ocular biometry, a standardised extracapsular cataract extraction with posterior chamber IOL implantation, and clinical refraction between 10 and 14 weeks post-operatively. RESULTS: There was no statistically significant difference between the two study groups in measured axial length (p > 0.01), calculated emmetropic IOL power (p > 0.05) or the prediction of post-operative refraction (p > 0.99). CONCLUSION: The use of a single high-quality axial length measurement was as accurate as the mean of three acceptable axial length measurements in the calculation of IOL power.

Cataract Extraction↗
PubMed1998

Prostate cancer and sexual function.

Erectile dysfunction is a condition affecting 1 in every 10 men. Although its occurrence is related to ageing, illness and its necessary therapy can play a major role. Prostate cancer can lead to erectile dysfunction both psychologically through depression and emotional distress, and physically through therapy for the disease. An international quality of life survey involving 401 patients with prostate cancer was conducted. The objectives of the study were to investigate the patients' understanding of the treatment options they received, to explore the importance of the patient-doctor communication in the treatment of prostate cancer and to see what effect treatment had on patient's sexual function. One of the main findings of the survey was that too little counselling or information on treatment options and their effects on sexual function was provided to patients. Patients themselves felt that psychosexual counselling, in particular, would be helpful. In addition, therapy for prostate cancer appears to have a significant impact on patients' lifestyle and also on their libido, sexual function and activity.

Journal Article↗
PubMed1998

The systemic stress response to thermal injury in children.

OBJECTIVE: Thermal injury is extremely stressful, but data characterizing the endocrine stress response to this injury in children are sparse. The objective of this study was to measure the effects of thermal injury on the levels of stress hormones in children and to assess the temporal changes associated with them. PATIENTS: Twenty-three children, 13 girls and 10 boys aged between 5 months and 12 years 3 months (mean, 2 years 11 months), with burns covering 10-61% of their body surface (mean, 20.5%) were studied during the first 5 days following injury. MEASUREMENTS: The levels of arginine vasopressin, angiotensin II, cortisol, adrenaline, noradrenaline and dopamine were measured in sequential blood samples obtained from thermally injured children on admission and at specified time intervals during the 5 days of the investigation. RESULTS: At admission the concentrations of all the hormones were high, and varied widely between individual patients. The geometric mean and 95% confidence intervals of admission hormone levels were as follows: arginine vasopressin 18.3 (8.3-40.7) pmol/l; angiotensin II 122.0 (56.0-266.2) pmol/l; cortisol 650.6 (473.0-895.0) nmol/l; dopamine 1.0 (0.1-8.0) nmol/l; adrenaline 6.4 (3.2-12.5) nmol/l and noradrenaline 2.3 (1.3-4.3) nmol/l. Although the concentrations of arginine vasopressin and cortisol returned to normal 24 to 36 h after admission, the levels of angiotensin II, adrenaline and dopamine fluctuated and remained higher than normal throughout the study (108 h). CONCLUSIONS: Thermal injury results in the release of abnormally high levels of stress hormones in children. Although there are similarities between some of the data reported here and those reported in adults, higher levels of adrenaline and lower levels of noradrenaline than reported in adults suggest important differences too. These differences may need to be taken into account in the management of burn-injured children.

Angiotensin II↗
PubMed1998

A field study of age and gender differences in habitual adult sleep.

The sleep of 52 healthy paid subjects (23 male) divided into three age-bands (20-34, 35-49 and 50-70 y) were recorded at night in their homes for a total of 190 subject-nights while following their normal daily activities and habitual sleep-wake schedule. There was a shortening in both nocturnal total sleep period and total sleep time (TST) with age, the oldest group sleeping 46 min less than the youngest. Also, the mid-point of sleep occurred 32 min earlier in the oldest group compared with the youngest group. The reduction in TST with age was due, in part, to increased wake periods within sleep. The youngest subjects showed more Movement Time which progressively decreased with age while the amount of stage 1 increased with age. The amount of slow-wave sleep (SWS, stages 3+4) was reduced, stage 4 was more than halved, while REM was slightly reduced with age. There were far fewer significant gender differences in the sleep variables: males, particularly in the middle and oldest age bands, had more stage 1 than females, while females had more SWS, particularly stage 3, than males. In general, despite relatively limited subject selection criteria, there was good agreement with previous laboratory-based normative sleep values for the effect of age and gender.

Adult↗
PubMed1998

Self-expanding metal oesophageal endoprostheses: which is best?

Palliation is necessary in over 50% of patients with oesophageal cancer, and the most effective means of achieving this is still debated. Plastic or stainless steel reinforced endoprostheses have been available for some 20 years, but have the disadvantages of bulky introducing systems, a significant incidence of perforation and, frequently, sub-optimal palliation. The introduction of self-expanding metallic stents (SEMS) in 1990 was received enthusiastically on account of their relative ease of insertion, with low perforation risk and greater internal diameter of 20-25 cm, resulting in better relief of dysphagia. However, disadvantages of SEMS include the high cost of the stents and disposable delivery systems, the difficulty in removing or repositioning these stents, and the high rate of re-intervention because of tumour ingrowth with uncovered stents, stent displacement with their covered counterparts, and obstruction owing to stent compression or tumour overgrowth at either end of the stent. Published studies include a randomized study between conventional plastic prostheses and uncovered Wallstents, a non-randomized study comparing uncovered Wallstents and Ultraflex stents, and the study published in this issue comparing uncovered Ultraflex stents with covered Wallstents. Somewhat surprisingly, 30 day mortality and relief of dysphagia were similar between conventional prostheses and uncovered Wallstents, and despite a 10-fold increase in cost of the SEMS over plastic prostheses, the overall cost of palliation was less because of a mean hospital stay of 5.4 days compared with 12.5 days for plastic prostheses, which is higher than many reported series and may relate to their insertion under general anaesthesia in this study. From the comparative studies of different SEMS, uncovered stents are associated with a higher incidence of tumour ingrowth and covered stents with a higher incidence of stent migration, particularly when they traverse the cardia. Thirty day mortality is relatively high (16-27%), although one study found no procedure-related mortality using the uncovered Ultraflex stent, but the reintervention rate was uniformly higher with those stents as compared with covered or uncovered Wallstents. Improvements in SEMS design are likely to overcome many of the technical problems, at which point it would be necessary to conduct prospective randomized studies against conventional prostheses inserted under sedation, with quality of life and economic assessment and sufficient numbers to enable sub-group analysis for variables such as tumour site and morphology. In the meantime, specialized centres should have facilities for each of the current palliative modalities so as to be able to deploy those most suited to individual circumstances.

Deglutition Disorders↗
PubMed1998

General practitioner screening for melanoma: sensitivity, specificity, and effect of training.

OBJECTIVE: To measure the performance of trained and untrained general practitioners (GPs) in screening men and women aged 50 or more for melanomas. METHODS: GPs trained in melanoma diagnosis, untrained GPs, and skin cancer specialists examined groups of volunteers, each of which included a small number of subjects with prediagnosed suspicious pigmented lesions (SPLs) that were subsequently excised for histopathological examination. RESULTS: Trained and untrained GPs achieved mean sensitivities of 0.73 and 0.71, and mean predictive values of 0.40 and 0.37, respectively, for the detection of prediagnosed SPLs. When the SPLs had been excised and examined histopathologically, reanalysis showed mean sensitivities of 0.98 and 0.95, mean specificities of 0.52 and 0.49, and mean positive predictive values of 0.24 and 0.22 for the detection of subjects with melanomas by trained and untrained GPs respectively. Trained GPs were significantly better than untrained GPs at diagnosing as melanomas SPLs that subsequently proved to be melanomas (p = 0.04). CONCLUSIONS: GPs in this study achieved high sensitivities in screening older Australian men and women for melanomas, but at the cost of low specificities and positive predictive values. Training in melanoma diagnosis had no significant effect on sensitivity, specificity, and positive predictive value for screening. Data from the study were tested in a model of population screening for melanomas, and costs per life year saved for men aged 50-70 ranged from $A11,852 to $A40,259 depending upon the screening interval and whether the GPs excised the SPLs diagnosed, or referred all patients to skin cancer specialists; this would be as cost effective as cervical cancer screening.

Female↗
PubMed1998

Update: total versus partial laparoscopic fundoplication.

Since the introduction of Nissen fundoplicaton in 1956, there has been concern about the incidence of troublesome mechanical complications, which has necessitated several modifications reducing the overall incidence to around 15%. Increasing knowledge of the pathophysiology of Nissen fundoplication has revealed that these complications are associated with a supracompetent high pressure zone (HPZ) which relaxes incompletely on swallowing and is associated with abolition of gas reflux and physiological acid reflux. Partial fundoplication procedures, which augment various constituents of the valvuloplasty component of competence and utilise a lesser degree of fundoplication, are associated with a very low incidence of mechanical complications, but debate has ensued that reflux control may be suboptimal and less durable than after Nissen fundoplication. However, several good, objective comparative studies and three prospective randomised trials have confirmed that a well conducted partial fundoplication procedure is at least as effective and durable in reflux control as Nissen fundoplication, whilst being associated with a lower incidence of mechanical complications. The debate has intensified since the advent of laparoscopic fundoplication, as several reports have highlighted the increased incidence of mechanical complications following Nissen fundoplication when performed laparoscopically compared with the open approach, with a higher incidence of impaired HPZ relaxation, believed to be associated with altered geometry and other factors inherent in laparoscopic fundoplication. This has resulted in re-operation rates for complications of laparoscopic Nissen fundoplication of 1-7%, and in the laparoscopic era, mechanical complications have overtaken recurrent reflux as the principal reason for revisional fundoplication. Several non-randomised series have shown that laparoscopic partial fundoplication procedures are associated with a similarly low incidence of mechanical complications and a negligible re-operation rate as at open operation, with retention of physiologial HPZ relaxation. These factors have resulted in increasing deployment of partial fundoplication procedures, and increasing support for the 'tailored' approach to anti-reflux surgery. Several prospective randomised studies between laparoscopic partial and total fundoplication procedures are currently in progress, and early results favour partial fundoplication because of the considerably lower incidence of mechanical complications. The continuance of these studies, as well as those underway which compare different partial fundoplication procedures and include economic and quality-of-life assessment, should enable the rational choice of the most appropriate laparoscopic anti-reflux procedure to be placed on a firm scientific footing.

Fundoplication↗