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Biomedical subjects

A D Shaw

Publications and source records attributed to A D Shaw.

At least 19 recordsLinked to original sources
PubMed2006

Effects of isoflurane, pentobarbital, and urethane on apoptosis and apoptotic signal transduction in rat kidney.

BACKGROUND: Renal cell apoptosis contributes significantly to the pathogenesis of acute renal failure. Anesthetic agents have been shown to modulate apoptotic signal transduction in various tissues. We examined the effects of 6 h of different general anesthetic techniques on renal cell apoptosis in rat kidneys. METHODS: Twenty-one male Sprague-Dawley rats were randomly allocated into four groups: (i) control, non-anesthetized rats (n= 3) and rats anesthetized with (ii) inhaled isoflurane (n= 6), (iii) intraperitoneal pentobarbital (n= 6), and (iv) intraperitoneal urethane (n= 6). Animals were sacrificed 6 h after the induction of anesthesia. RESULTS: Apoptosis was assessed by terminal deoxynucleotidyl transferase-fluorescein end-labeling analysis. RNA was extracted from the left kidney to probe cDNA microarrays. Gene expression was measured as a percentage of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and subsequently confirmed using reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the control (no anesthesia), urethane significantly (P < 0.001) induced apoptosis in both the renal cortex and medulla. Isoflurane significantly (P < 0.001) inhibited apoptosis in the medulla. Microarray analysis revealed that urethane up-regulated more (74) genes than pentobarbital (16) and isoflurane (10). Isoflurane down-regulated more genes (85) than pentobarbital (74) and urethane (12). These anesthetic-induced modulations were significant (P < 0.05) for 60 isoflurane-, 30 pentobarbital- and 4 urethane-modulated genes. CONCLUSION: Our results suggest that general anesthetic drugs have an effect on renal cell apoptosis and apoptotic signal transduction, and thus may potentially affect the risk of subsequent acute renal failure.

Animals↗
PubMed2005

Transcriptional responses of rat skeletal muscle following hypoxia-reoxygenation and near ischaemia-reperfusion.

AIM: The effect of ischaemia/reperfusion or hypoxia/reoxygenation on gene expression has not been extensively studied. We hypothesized that in skeletal muscle, tissue hypoxia of similar magnitude but induced by different mechanisms would lead to different transcriptional responses. METHODS: Muscle gene transcription was assessed using microarray analysis and reverse transcriptase polymerase chain reaction in 18 rats exposed to regional hind limb near ischaemia/reperfusion (n = 6), hypoxia/reoxygenation (n = 6) or sham operation (n = 6). Hypoxic burden was measured by the area under the PtO(2)-time curve. RESULTS: PtO(2) was reduced in both the near ischaemia/reperfusion and hypoxia/reoxygenation groups. Although the hypoxic burden was similar, the genomic response was different for each condition. Near ischaemia/reperfusion had a greater effect on gene expression than hypoxia/reoxygenation. Using stringent criteria for changes in gene expression (i.e. more than or equal to twofold change vs. control) unique patterns of gene expression could be identified suggesting individualized transcriptional responses to each of these injuries. Several genes, including insulin-like growth factor 1 (IGF-1) and cyclin-dependent kinase inhibitor (p27(Kip1)) were induced by both injury types and these may have potential clinical application as markers of tissue damage. In contrast, no single gene was downregulated by both injury conditions. CONCLUSIONS: The mechanism of skeletal muscle hypoxia has a profound effect on its subsequent transcriptional response. We identified several potential candidates as markers of skeletal muscle ischaemic damage.

Animals↗
PubMed2004

Daystay hamstring ACL reconstruction performed under regional anaesthesia.

Daycase ACL reconstruction is commonly performed under general anaesthesia with a patella tendon graft. We report our experience with hamstring reconstruction under regional anaesthesia. Over a 14-month period, 104 daycase arthroscopic ACL reconstructions were performed by one surgeon and one anaesthetist. All operations were performed under spinal anaesthesia with a femoral nerve block. Patients were discharged with oral analgesia, brace and a cryocuff. One hundred and two patients were prospectively evaluated with a visual analogue pain score (0-10) and a patient satisfaction questionnaire. Of these 102 patients, 101 (99%) were happy to be discharged on the same day. One patient was admitted from the daycase unit, and one patient was re-admitted. Patients were very satisfied with the pain relief provided. The mean visual analogue pain score was 1.0 at discharge, 1.8 in the middle of the first night, and 2.1 on the first post-op day. Patients experienced significantly more pain the day after surgery than the evening of surgery (p=0.04). We conclude that hamstring ACL reconstruction under regional anaesthesia is well tolerated by patients as a daycase procedure.

Ambulatory Care↗
PubMed2002

Primary and secondary metabolism, and post-translational protein modifications, as portrayed by proteomic analysis of Streptomyces coelicolor.

The newly sequenced genome of Streptomyces coelicolor is estimated to encode 7825 theoretical proteins. We have mapped approximately 10% of the theoretical proteome experimentally using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Products from 770 different genes were identified, and the types of proteins represented are discussed in terms of their annotated functional classes. An average of 1.2 proteins per gene was observed, indicating extensive post-translational regulation. Examples of modification by N-acetylation, adenylylation and proteolytic processing were characterized using mass spectrometry. Proteins from both primary and certain secondary metabolic pathways are strongly represented on the map, and a number of these enzymes were identified at more than one two-dimensional gel location. Post-translational modification mechanisms may therefore play a significant role in the regulation of these pathways. Unexpectedly, one of the enzymes for synthesis of the actinorhodin polyketide antibiotic appears to be located outside the cytoplasmic compartment, within the cell wall matrix. Of 20 gene clusters encoding enzymes characteristic of secondary metabolism, eight are represented on the proteome map, including three that specify the production of novel metabolites. This information will be valuable in the characterization of the new metabolites.

Acetylation↗
PubMed2001

Influence of an advance directive on the initiation of life support technology in critically ill cancer patients.

OBJECTIVE: To determine whether the presence of an advance directive at admission to an intensive care unit (ICU) influenced the decision to initiate life support therapy in critically ill cancer patients. DESIGN: Matched-pairs case-control design. SETTING: The University of Texas M. D. Anderson Cancer Center ICU. PATIENTS: Of 872 patients treated in the ICU from 1994 to 1996, 236 (27%) were identified as having advance directives. One hundred thirty five patients who had advance directives were successfully matched to 135 patients who did not on the basis of type of malignancy, reason for admission to ICU, severity of illness, and age. These pairs comprised the study group. INTERVENTIONS: Life-supporting interventions were compared between the matched groups using the McNemar and Wilcoxon matched-pairs signed ranks tests. MEASUREMENTS AND MAIN RESULTS: No significant difference was found in the frequency with which the following interventions were applied in patients with and without advance directives (respectively): mechanical ventilation, 44% vs. 42%; inotropic support, 31% vs. 31%; pulmonary artery catheterization, 11% vs. 12%; cardiopulmonary resuscitation, 7% vs. 12%; and renal dialysis, 3% vs. 7%. There were also no differences in ICU (75% vs. 73%, respectively) or hospital (56% vs. 59%, respectively) survival. More patients with advance directives than those without had do-not-resuscitate orders within the first 72 hrs (19% vs. 11%, p =.046) and patients with advance directives had shorter ICU durations and lower ICU charges than patients without advance directives. CONCLUSIONS: After controlling for type of malignancy, reason for admission to the ICU, severity of illness, and age, the decision to initiate life-supporting interventions did not differ significantly among patients with and without advance directives. The presence of an advance directive, however, may have helped guide decisions earlier regarding duration of therapy and resuscitation status.

Adult↗
PubMed2000

Rapid analysis of high-dimensional bioprocesses using multivariate spectroscopies and advanced chemometrics.

There are an increasing number of instrumental methods for obtaining data from biochemical processes, many of which now provide information on many (indeed many hundreds) of variables simultaneously. The wealth of data that these methods provide, however, is useless without the means to extract the required information. As instruments advance, and the quantity of data produced increases, the fields of bioinformatics and chemometrics have consequently grown greatly in importance. The chemometric methods nowadays available are both powerful and dangerous, and there are many issues to be considered when using statistical analyses on data for which there are numerous measurements (which often exceed the number of samples). It is not difficult to carry out statistical analysis on multivariate data in such a way that the results appear much more impressive than they really are. The authors present some of the methods that we have developed and exploited in Aberystwyth for gathering highly multivariate data from bioprocesses, and some techniques of sound multivariate statistical analyses (and of related methods based on neural and evolutionary computing) which can ensure that the results will stand up to the most rigorous scrutiny.

Algorithms↗
PubMed2000

Effect of ispaghula husk on the faecal output of bile acids in healthy volunteers.

Faecal bile acids are associated with both colorectal cancer and serum cholesterol levels. We investigate whether dosing with ispaghula husk affects the faecal bile acid weights and concentrations in healthy adults. Sixteen healthy volunteers consumed 7.0 g/day ispaghula husk, containing 5.88 g/day Englyst-determinable dietary fibre, for the middle 8 weeks of a 12-week period. Stool samples were collected, analysed for faecal bile acids and their form and dry weight determined. Correlations between the faecal bile acids, the stool parameters and the dietary intake were tested. Ispaghula husk treatment significantly lowers faecal lithocholic and isolithocholic acids and the weighted ratio of lithocholic acids to deoxycholic acid. These effects revert towards their initial states at the end of the treatment period. These changes in the faecal bile acid profiles indicate a reduction in the hydrophobicity of the bile acids in the enterohepatic circulation.

Adult↗
PubMed2000

Monitoring ventilator weaning--predictors of success.

Improving the prediction of successful ventilator weaning and extubation is a goal that all Intensivists and perioperative physicians strive for. The successful wean and extubation of ventilated patients decreases hospital length of stay and associated costs, but more importantly it also reduces patient morbidity and mortality. This review evaluates traditional and novel indices used in the assessment for ventilatory wean readiness. Novel equipment such as the Bicore pulmonary monitor and the CO2 SMO Plus are now available on the market to assess and monitor ventilator weaning and may offer some value in this process. We also review the non-respiratory factors affecting weaning and the role of the bedside nurse and respiratory therapist. Resolution of the pulmonary compromise and an understanding of respiratory physiology, used in conjunction with monitored indices of weaning parameters in a consistent fashion will continue to improve our success rates of ventilator weaning and extubation.

Humans↗
PubMed1999

Variable selection and multivariate methods for the identification of microorganisms by flow cytometry.

BACKGROUND: When exploited fully, flow cytometry can be used to provide multiparametric data for each cell in the sample of interest. While this makes flow cytometry a powerful technique for discriminating between different cell types, the data can be difficult to interpret. Traditionally, dual-parameter plots are used to visualize flow cytometric data, and for a data set consisting of seven parameters, one should examine 21 of these plots. A more efficient method is to reduce the dimensionality of the data (e.g., using unsupervised methods such as principal components analysis) so that fewer graphs need to be examined, or to use supervised multivariate data analysis methods to give a prediction of the identity of the analyzed particles. MATERIALS AND METHODS: We collected multiparametric data sets for microbiological samples stained with six cocktails of fluorescent stains. Multivariate data analysis methods were explored as a means of microbial detection and identification. RESULTS: We show that while all cocktails and all methods gave good accuracy of predictions (>94%), careful selection of both the stains and the analysis method could improve this figure (to > 99% accuracy), even in a data set that was not used in the formation of the supervised multivariate calibration model. CONCLUSIONS: Flow cytometry provides a rapid method of obtaining multiparametric data for distinguishing between microorganisms. Multivariate data analysis methods have an important role to play in extracting the information from the data obtained. Artificial neural networks proved to be the most suitable method of data analysis.

Bacillus subtilis↗
PubMed1999

Lactose intolerance: problems in diagnosis and treatment.

Lactose malabsorption and lactase deficiency are chronic organic pathologic conditions characterized by abdominal pain and distention, flatulence, and the passage of loose, watery stools. Though malabsorption of the sugar lactose is determinable by breath hydrogen test or jejunal biopsy, intolerance can only be confirmed by challenge with lactose-containing food, the response to which may not be immediate. The difficulty of making a positive diagnosis of these conditions has led to a proportion of lactose-intolerant patients being misdiagnosed with irritable bowel syndrome (IBS), which has a remarkably similar symptom complex and for which there is no current pathophysiologic marker. The incidence of the two disorders is approximately equal, but the actual proportion of patients with IBS incorrectly diagnosed in this way varies as a function of the methodology used. Once correct diagnosis is established, introduction of a lactose-free dietary regime relieves symptoms in most patients. Symptom similarity and the resultant incorrect diagnosis of IBS may explain the refractory nature of some patients labeled as IBS who remain largely unaware of the relationship between food intake and symptoms.

Breath Tests↗
PubMed1998

Anaesthesia for video-assisted thoracoscopic patent ductus arteriosus ligation.

The case notes of children undergoing video-assisted thoracoscopic ligation of a patent ductus arteriosus were reviewed with particular emphasis on the anaesthetic management. All children were managed using one-lung ventilation with no serious adverse sequelae. The lungs could be isolated easily in all cases and no special equipment was required. We describe our initial series of 13 cases and discuss the anaesthetic implications arising from this surgical technique. We also discuss the different ways of monitoring duct closure.

Anesthesia, Inhalation↗
PubMed1998

Nitrous oxide and carbon dioxide have no effect on the blood-gas solubilities of sevoflurane and isoflurane.

UNLABELLED: Nitrous oxide (N2O) has been shown to decrease the solubility (lambdaB:G) of volatile anesthetics in human blood and, consequently, affect their rate of uptake. If this is true, then carbon dioxide (CO2) may also have an effect, which is important because methods that measure the tension of volatile anesthetics in blood washout CO2 in the process. Blood samples were obtained from fasted, healthy volunteers and patients undergoing major surgery. Each sample was divided into two aliquots: one was equilibrated at 37 degrees C in a closed glass tonometer with a mixture of isoflurane 1% and sevoflurane 2% in a test gas mixture of either 50:50 N2O/O2 or 5:95 CO2/O2; the other aliquot was equilibrated with isoflurane and sevoflurane in O2 alone as a control. Using a two-stage headspace technique using gas chromatography, we measured the lambdaB:G of isoflurane and sevoflurane in the presence and absence of the test gas in each subject. There was no significant difference between the lambdaB:G of sevoflurane and isoflurane obtained from the N2O group and their controls or between the CO2 group and their controls. We conclude that neither N2O nor CO2 has an effect on the lambdaB:G of sevoflurane or isoflurane in the concentrations tested. IMPLICATIONS: The blood solubilities of sevoflurane and isoflurane were measured with and without nitrous oxide and carbon dioxide. No differences were found. Nitrous oxide does not affect the kinetics of other anesthetics by altering their solubility. Carbon dioxide tensions need not be controlled when measuring anesthetic tensions in blood.

Anesthetics, Inhalation↗
PubMed1998

The island posterior calf fasciocutaneous flap: an alternative to the gastrocnemius muscle for cover of knee and tibial defects.

The gastrocnemius muscle remains the workhorse for providing soft tissue over the knee and upper tibia. Nevertheless, we have found the island posterior calf fasciocutaneous flap to be a valuable alternative. We describe 10 cases in which an island posterior calf fasciocutaneous flap was used to cover defects over the knee and tibia. Three cases were after knee arthroplasty wound dehiscence, three cases were of traumatic soft-tissue loss, three cases involved replacement of unstable skin, and one case required closing a synovial fistula. This series is compared with 10 contemporaneous consecutive cases of soft-tissue loss around the knee that were reconstructed with a gastrocnemius muscle flap. Nine posterior calf fasciocutaneous flaps survived completely, and one flap had to be replaced because of poor flow. Although this flap is technically more demanding, we have found that it offers some advantages over the gastrocnemius. These include a greater flexibility of size and shape, a longer arc of rotation to reach suprapatellar defects, the provision of sensate skin with protective though crude sensation, less bulk, and the avoidance of a twitch. The flap is also easy to re-elevate from the recipient site for subsequent orthopedic work.

Adolescent↗