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S J Wright

Publications and source records attributed to S J Wright.

At least 37 records · Page 2Linked to original sources
PubMed1998

Thoracic electrical bioimpedance: a non-invasive measure of cardiac output for porcine research.

A comparison of two techniques for measuring cardiac output, thermodilution (TD) and thoracic electrical bioimpedance (TEB), was undertaken in a porcine model. Eight anaesthetized large white pigs were studied. A total of 436 paired measurements were performed over a range of cardiac outputs from 1.7 to 15.1 l/min as measured by thermodilution. The Pearson product moment correlation coefficient was r = 0.963 with P < 0.001. Analysis by Bland and Altman statistics revealed a mean difference (bias) of -0.02 l/min and the limits of agreement were +/- 1.6 l/min, similar to figures found in human comparative studies. These results confirm that thoracic electrical bioimpedance is a valid method of measuring cardiac output in pigs. It has significant advantages compared to thermodilution, in particular it is cheap, simple to use, non-invasive and provides continuous data.

Animals↗
PubMed1997

Validation of thoracic electrical bioimpedance as a porcine research tool.

We have compared the accuracy of two methods of measuring cardiac output, thoracic electrical bioimpedance (TEB) and thermodilution (TD), in pigs. We studied four anaesthetized pigs, producing 145 paired cardiac output values over a range of TD cardiac outputs of 2.6-12.6 litre min-1. TEB cardiac output was less than that measured by TD, by a constant factor throughout the observed range of values, because of differences in porcine thoracic shape. The Pearson product moment correlation coefficient suggested a good correlation (r = 0.984, P < 0.001). More importantly, analysis by the Bland and Altman statistical method suggested a high level of agreement, with 95% confidence intervals of +/- 1.0 litre min-1. These results suggest that TEB can be used as a satisfactory method to measure cardiac output in porcine models.

Animals↗
PubMed1996

Central venous pressure in space.

Gravity affects cardiac filling pressure and intravascular fluid distribution significantly. A major central fluid shift occurs when all hydrostatic gradients are abolished on entry into microgravity (microG). Understanding the dynamics of this shift requires continuous monitoring of cardiac filling pressure; central venous pressure (CVP) measurement is the only feasible means of accomplishing this. We directly measured CVP in three subjects: one aboard the Spacelab Life Sciences-1 space shuttle flight and two aboard the Spacelab Life Sciences-2 space shuttle flight. Continuous CVP measurements, with a 4-Fr catheter, began 4 h before launch and continued into microG. Mean CVP was 8.4 cmH2O seated before flight, 15.0 cmH2O in the supine legs-elevated posture in the shuttle, and 2.5 cmH2O after 10 min in microG. Although CVP decreased, the left ventricular end-diastolic dimension measured by echocardiography increased from a mean of 4.60 cm supine preflight to 4.97 cm within 48 h in microG. These data are consistent with increased cardiac filling early in microG despite a fall in CVP, suggesting that the relationship between CVP and actual transmural left ventricular filling pressure is altered in microG.

Adult↗
PubMed1996

Orthostatic intolerance after spaceflight.

Orthostatic intolerance occurs commonly after spaceflight, and important aspects of the underlying mechanisms remain unclear. We studied 14 individuals supine and standing before and after three space shuttle missions of 9-14 days. After spaceflight, 9 of the 14 (64%) crew members could not complete a 10-min stand test that all completed preflight. Pre- and postflight supine hemodynamics were similar in both groups except for slightly higher systolic and mean arterial pressures preflight in the finishers [15 +/- 3.7 and 8 +/- 1.2 (SE) mmHg, respectively; P < 0.05]. Postflight, finishers and nonfinishers had equally large postural reductions in stroke volume (-47 +/- 3.7 and -48 +/- 3.3 ml, respectively) and increases in heart rate (35 +/- 6.6 and 51 +/- 5.2 beats/min, respectively). Cardiac output during standing was also similar (3.6 +/- 0.4 and 4.1 +/- 0.3 l/min, respectively). However, the finishers had a greater postflight vasoconstrictor response with higher total peripheral resistance during standing (22.3 +/- 1.2 units preflight and 29.4 +/- 2.3 units postflight) than did the nonfinishers (20.1 +/- 1.1 units preflight and 19.9 +/- 1.4 units postflight). We conclude that 1) the primary systemic hemodynamic event, i.e., the postural decrease in stroke volume, was similar in finishers and nonfinishers and 2) the heart rate response and cardiac output during standing were not significantly different, but 3) the postural vasoconstrictor response was significantly greater among the finishers (P < 0.01).

Adult↗
PubMed1995

Protein tyrosine phosphorylation during sea urchin fertilization: microtubule dynamics require tyrosine kinase activity.

Protein tyrosine phosphorylation plays an important role in cell growth, mitosis, and tumorigenesis. It has also been implicated in meiotic maturation and fertilization. We have used anti-phosphotyrosine immunofluorescence and immunoblotting to identify sperm and egg proteins which are phosphorylated on tyrosine residues prior to and during sea urchin fertilization. On immunoblots of sperm proteins, the monoclonal anti-phosphotyrosine antibody detected three major proteins with molecular weights of 44, 82, and 100 kD, and six minor bands at 46, 48, 70, 76, 95, and 150 kD. These phosphotyrosyl proteins were localized to the sperm acrosomal and centriolar fossae. In contrast, staining was found globally in unfertilized eggs, and the antibody recognized two major egg phosphotyrosyl proteins of molecular weights 42 and 50 kD, and five minor bands at 40, 90, 116, 130, and 150 kD. While immunofluorescent staining remained throughout the fertilized egg cytoplasm, there were dynamic changes in the staining intensity of single bands. The 90 kD immunoreactive band increased in intensity, and the 40 and 42 kD bands disappeared by 15 min after fertilization. Loss of the 40 and 42 kD bands was due to dephosphorylation by okadaic acid-sensitive phosphatase(s). The 50 kD immunoreactive protein was unchanged up to the 8-cell stage and was still present in blastulae, indicating its importance throughout fertilization and early development. Alterations in the pattern of phosphotyrosine-containing proteins during fertilization did not depend on nascent proteins and could not be completely mimicked by increasing intracellular calcium, pH, and protein kinase C activity alone. Since changes in the fertilization pattern of phosphotyrosyl proteins occurred during formation of the sperm aster and mitotic spindle, we analyzed the role of protein tyrosine kinase activity in these processes using the tyrosine kinase specific inhibitor, erbstatin. Both the sperm aster and mitotic spindle were disrupted, indicating an involvement of tyrosine phosphorylation in these processes during interphase and mitosis. We conclude that the changes in phosphotyrosyl proteins play an important role in fertilization and early development of sea urchin eggs. Control of microtubule assembly into the sperm aster and mitotic spindle of the first cell cycle are examples of such roles.

Animals↗
PubMed1995

Direct analysis of polycyclic aromatic hydrocarbons in cloud-water aerosol filtrates using laser desorption mass spectrometry.

A novel technique for the rapid screening of polyaromatic hydrocarbons (PAHs) in atmospheric particulates is presented. Two-step laser desorption laser photoionisation time-of-flight mass spectrometry was used to assay for PAHs in cloud-water particulates collected near Peebles in southern Scotland. The particulates were examined in situ on their host filters removing the requirement for time-consuming sample extraction and separation. The mass spectra obtained from a single filter are shown. The principal components of these are assigned to PAH contaminants and phthalate contaminants. A distribution of PAHs was observed using 193 nm laser photoionisation. The mass spectrum obtained on using 248 nm laser photoionisation exhibits a different intensity distribution demonstrating an ionisation wavelength dependence. The utility of the technique for rapid screening of PAHs and other polyaromatic species is discussed.

Journal Article↗
PubMed1995

Antibacterial activity of the anti-inflammatory compound ibuprofen.

The effect of ibuprofen on growth in vitro of six bacterial species was tested. Ibuprofen inhibited growth of the Gram-positive species, but the two Gram-negative species were unaffected. Growth of Staphylococcus aureus was suppressed by ibuprofen concentrations greater than 150 micrograms ml-1 at initial pH 7. At pH 6, such concentrations prevented growth. The antibacterial activity of ibuprofen was affected by pH, being more effective at values below pH 7. Ibuprofen may have an ancillary benefit in topical application, in controlling bacteria.

Dose-Response Relationship, Drug↗
PubMed1995

The cerebral function monitor (CFM) is a useful addition to a bilateral carotid artery, vein graft model.

Following human coronary artery bypass surgery, vein graft occlusion is a major cause of morbidity and mortality. An agent is required which will reduce the incidence of early graft thrombosis without causing systemic bleeding. To assess the efficacy of such agents a suitable experimental vein-graft model is required. A porcine, unilateral saphenous vein-carotid artery bypass graft model has been described previously, although to assess the effect of locally applied anticoagulant drugs, insertion of grafts bilaterally would be advantageous, allowing treated and control grafts to be implanted in the same animal which would then act as its own control. Pigs are reported as having an excellent collateral cerebral circulation and hence in theory, would be suitable animals to use as a bilateral carotid vein-graft model. This paper describes the occurrence of serious neurological complications during the development of such a model and suggests that by using a cerebral function monitor, detection of critical reductions in cerebral perfusion can be made early and remedial action take.

Animals↗
PubMed1995

Cyclosporine A in chronic lymphocytic leukemia: dual anti-leukemic and immunosuppressive role?

The association of hemolytic anemia and other autoimmune cytopenias with chronic lymphocytic leukemia (CLL) is well known. The etiology of these immune syndromes is still uncertain, despite evidence that the putative cell of origin of the B-CLL cell produces naturally occurring autoantibodies. Cyclosporine A is effective in treating the immune manifestations associated with CLL and, occasionally, has shown anti-leukemic activity. We report two cases in which cyclosporine A treatment of autoimmune hemolytic anemia resulted in reduction of CLL cell burden. We then discuss the possible mechanism of action of cyclosporine A and the nature of the autoimmune processes involved.

Adult↗
PubMed1995

Cytogenetic response to alpha-interferon is predicted in early chronic phase chronic myeloid leukemia by M-bcr breakpoint location.

Alpha-interferon (alpha-IFN) therapy is an effective agent in early chronic phase (ECP) chronic myeloid leukemia (CML), achieving hematologic control in the majority and major cytogenetic response (MCR) (reduction in Ph' +ve metaphases to < 35%) in a substantial minority. Currently no pretreatment markers exist to ascertain likelihood of meaningful response. The site of breakpoint in M-bcr and relationship to prognosis is controversial. Studies have been hampered by variation in definition of breakpoint and difference in treatment protocols. In this study of ECP CML patients, Southern analysis and reverse transcription polymerase chain reaction (RT-PCR) were used to determine breakpoint location. Patients received alpha-IFN (9 x 10(6) units/day) and dose-adjusted hydroxyurea (HU) to maintain granulocyte count between 1.0-2.0 x 10(9)/l for 6 months or more. Twelve of 31 patients entered on the study achieved a MCR. The Sokal index did not predict for cytogenetic response to alpha-IFN. Eight of 11 patients with 5' breakpoint achieved MCR compared to only four of 20 patients with 3' breakpoint (P = 0.007). These results suggest site of M-bcr rearrangement may be predictive of response to alpha-IFN therapy. If verified by further study, this may allow more appropriate use of alpha-IFN with respect to other modalities such as allogeneic transplant.

Base Sequence↗
PubMed1994

The role of fludarabine in hematological malignancies.

Fludarabine monophosphate, a synthetic nucleoside analog, has been shown to have considerable activity in a number of lymphoid malignancies. In chronic lymphocytic leukemia the response rates can exceed 70% with a considerable proportion of complete remissions being attained. These rates are markedly superior to earlier therapies with which complete remission was uncommon. It also has significant activity in previously treated patients for whom effective salvage regimens were unsatisfactory. In addition, fludarabine shows substantial activity in low grade non-Hodgkin's lymphoma, both as initial treatment and as salvage therapy. Fludarabine is effective in Waldenstrom's macroglobulinemia and is active in other low grade lymphoid malignancies. Major toxicities are reversible myelosuppression and depletion of T lymphocytes. The use of fludarabine in hematological malignancies will be reviewed, with reference to its mode of action and future use in combination therapies.

Adult↗
PubMed1993

Calculating the protamine-heparin reversal ratio: a pilot study investigating a new method.

There is no consensus as to the dosage of protamine required to reverse a given dose of heparin. The amounts advised vary widely. The hypothesis was investigated that doses of protamine smaller than those usually recommended could be used following cardiac surgery to successfully reverse heparin activity as measured by the activated coagulation time (ACT). A group of 18 patients scheduled for cardiopulmonary bypass (CPB) were investigated with their informed consent. A baseline ACT was measured before anticoagulation with heparin. At the end of CPB, an initial neutralizing dose (IND) of protamine (2 mg/kg) was administered. The ACT was measured after 5 minutes and a further dose of protamine (2 mg/kg) was then administered to make up the full dose. The heparin activity (HA) before and after the IND of protamine reversal was calculated according to the method described by Bull. The IND of protamine (2 mg/kg) was expressed as a ratio of the change in HA (the latter also expressed as mg/kg). The average +/- standard deviation (SD) preoperative ACT was 155 +/- 21 seconds with a range of 130 to 199 seconds. Following heparin administration the ACT increased to 701 +/- 152 seconds. After the IND of protamine, the average ACT of 160 +/- 31 (range, 121 to 250) was not statistically (NS) significantly different from the starting value. A further dose of 2 mg/kg of protamine ("full-dose") decreased (NS) the ACT only minimally to an average of 151 +/- 18 (range, 128 to 206) seconds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Discordant neutrophil alkaline phosphatase activity and cytogenetic response in chronic myeloid leukemia treated with alpha-interferon.

Decreased neutrophil alkaline phosphatase (NAP) synthesis is a classical feature of Philadelphia (Ph) positive chronic phase chronic myeloid leukemia (CML). Whether this aberration is an integral leukemic property of the cell or results from mediation by other factors is unclear. During alpha-interferon (alpha-IFN) based therapy the relationship between Ph chromosome suppression and NAP synthesis was examined. Four categories of response were observed in 19 patients studied sequentially. Significantly, persistent low NAP activity was observed in one patient in complete cytogenetic remission, while a second group of 7 patients demonstrated normal NAP activity in spite of persistence of the Ph chromosome in 100% of metaphases. In the absence of various clinical influences that can modulate NAP activity in chronic phase CML, the results reinforce the observation that the BCR/ABL fusion gene product is not a key factor influencing NAP activity in CML.

Adult↗
PubMed1992

Contrasting leaf phenotypes control seasonal variation in water loss in a tropical forest shrub.

Psychotria marginata, a shrub common to humid tropical forests in Central America, produces leaves in two seasonal flushes with contrasting morphology and physiology. Leaf production is bimodal with a major peak at the beginning of the annual wet season and a secondary peak at the end of the wet season. Together these peaks account for 75-87% of annual leaf production. Leaves produced just prior to the dry season have higher specific mass and, during drought, have lower stomatal conductances and higher water-use efficiencies. Plants irrigated during two consecutive dry seasons continued to produce leaves with these morphological and physiological differences, indicating that this feature has been strongly canalized by some factor other than water availability in this highly predictable yet seasonal habitat. The bimodal leaf production results in acclimation to changing conditions through co-occurring leaves that lack the physiological plasticity usually associated with acclimation. Heterophylly of this form suggests that the moderate drought of the dry season has been a significant selective factor for understory plants.

Journal Article↗
PubMed1992

Granulocyte colony stimulating factor in the management of chronic neutropenia.

OBJECTIVE: To report two cases of chronic neutropenic states successfully treated with granulocyte colony stimulating factor (G-CSF). CLINICAL FEATURES: A 23-year-old man with severe congenital cyclic neutropenia causing lifelong recurrent infections and consequent debilitation presented with intractable infected leg ulcers. A 56-year-old man with acquired idiopathic neutropenia presented with severe perianal infection and sepsis. INTERVENTION AND OUTCOME: Both patients were successfully treated with recombinant G-CSF. CONCLUSION: G-CSF is an agent with major clinical potential for the therapy of primary neutropenic states.

Adult↗