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Biomedical subjects

S J Wright

Publications and source records attributed to S J Wright.

At least 19 recordsLinked to original sources

Is transcutaneous electrical nerve stimulation an effective analgesia during colonoscopy?

OBJECTIVES: To evaluate the efficacy of transcutaneous electrical nerve stimulation (TENS) as analgesia during colonoscopy. DESIGN: In a randomised controlled trial, patients undergoing diagnostic colonoscopy were assigned to one of three groups: standard medication only (midazolam); active TENS plus standard medication; or non-functioning TENS and standard medication. Efficacy of TENS was determined using numerical rating scores for pain and the post-procedural evaluation questionnaire. SETTING: Patients undergoing diagnostic colonoscopy in a teaching hospital. MAIN OUTCOME: There was no statistically significant differences between the three groups. However in the active TENS group there was a greater variation in "physical discomfort" and "psychological distress", suggesting TENS may be effective in subgroup of patients.

Adult↗

Effects of spaceflight on human calf hemodynamics.

Chronic microgravity may modify adaptations of the leg circulation to gravitational pressures. We measured resting calf compliance and blood flow with venous occlusion plethysmography, and arterial blood pressure with sphygmomanometry, in seven subjects before, during, and after spaceflight. Calf vascular resistance equaled mean arterial pressure divided by calf flow. Compliance equaled the slope of the calf volume change and venous occlusion pressure relationship for thigh cuff pressures of 20, 40, 60, and 80 mmHg held for 1, 2, 3, and 4 min, respectively, with 1-min breaks between occlusions. Calf blood flow decreased 41% in microgravity (to 1.15 +/- 0.16 ml x 100 ml(-1) x min(-1)) relative to 1-G supine conditions (1.94 +/- 0.19 ml x 100 ml(-1) x min(-1), P = 0.01), and arterial pressure tended to increase (P = 0.05), such that calf vascular resistance doubled in microgravity (preflight: 43 +/- 4 units; in-flight: 83 +/- 13 units; P < 0.001) yet returned to preflight levels after flight. Calf compliance remained unchanged in microgravity but tended to increase during the first week postflight (P > 0.2). Calf vasoconstriction in microgravity qualitatively agrees with the "upright set-point" hypothesis: the circulation seeks conditions approximating upright posture on Earth. No calf hemodynamic result exhibited obvious mechanistic implications for postflight orthostatic intolerance.

Adult↗

Pervasive density-dependent recruitment enhances seedling diversity in a tropical forest.

Negative density-dependent recruitment of seedlings, that is, seeds of a given species are less likely to become established seedlings if the density of that species is high, has been proposed to be an important mechanism contributing to the extraordinary diversity of tropical tree communities because it can potentially prevent any particular species from usurping all available space, either in close proximity to seed sources or at relatively larger spatial scales. However, density-dependent recruitment does not necessarily enhance community diversity. Furthermore, although density-dependent effects have been found at some life stages in some species, no study has shown that density-dependent recruitment affects community diversity. Here we report the results of observations in a lowland, moist forest in the Republic of Panamá in which the species identities of 386,027 seeds that arrived at 200 seed traps were compared with the species identities of 13,068 seedlings that recruited into adjacent plots over a 4-year period. Across the 200 sites, recruit seedling diversity was significantly higher than seed diversity. Part of this difference was explained by interspecies differences in average recruitment success. Even after accounting for these differences, however, negative density-dependent recruitment contributes significantly to the increase in diversity from seeds to seedling recruits.

Genetic Variation↗

Essential thrombocythaemia.

Essential thrombocythaemia (ET) is a clonal stem cell disorder that frequently presents as an incidental finding of elevated platelet counts. Diagnosis depends on exclusion of other myeloproliferative disorders and reactive thrombocytosis. Patients with platelet counts above 1000 x 10(9)/L should receive platelet-lowering therapy, even if asymptomatic. Definitive recommendations cannot yet be made for asymptomatic patients with lower platelet counts. ET can be treated with alkylating agents, radioactive phosphorus or hydroxyurea, but there is evidence that these agents increase transformation to acute leukaemia. Interferon alfa-2a and anagrelide are useful treatment agents, particularly in younger patients.

Diagnosis, Differential↗

Sperm nuclear activation during fertilization.

The delivery of the paternal genome to the egg is a primary goal of fertilization. In preparation for this step, the nucleus of the developing spermatozoon undergoes extensive morphological and biochemical transformations during spermatogenesis to yield a tightly compacted sperm nucleus. These modifications are essentially reversed during fertilization. As a result, the incorporated sperm nucleus undergoes many steps in the egg cytoplasm as it develops into a male pronucleus. The sperm nucleus (1) loses its nuclear envelope, (2) undergoes nucleoprotein remodeling, (3) decondenses and increases in size, (4) becomes more spherical, (5) acquires a new nuclear envelope, and (6) becomes functionally competent to synthesize DNA and RNA. These changes are coordinate with meiotic processing of the maternal chromatin, and often result in behaviors asynchronous with the maternal chromatin. For example, in eggs fertilized during meiosis, the sperm nucleus decondenses while the maternal chromatin remains condensed. A model is presented that suggests some reasons why this puzzling behavior exists. Defects in any of the processes attending male pronuclear development often result in infertility. New assisted reproductive technologies have been developed that ensure delivery of the sperm nucleus to the egg cytoplasm so that a healthy embryo is produced. An emerging challenge is to further characterize the molecular mechanisms that control sperm nuclear transformations and link these to causes of human infertility. Further understanding of this basic process promises to revolutionize our understanding of the mystery of the beginning of new life.

Animals↗

Efficacy, safety and tolerability of anagrelide in the treatment of essential thrombocythaemia.

BACKGROUND: Essential thrombocythaemia (ET) has an associated risk of thrombotic and haemorrhagic complications, which can be minimised by control of the platelet count. Anagrelide selectively lowers the platelet count, however, there is little Australasian experience with its use and scant data on symptom control. AIMS: To evaluate the efficacy of anagrelide for platelet reduction and symptom control in a broad cohort of patients with well-defined ET, and to determine the safety and tolerability in such a population. METHODS: Seventeen patients with ET and a platelet count > 600 x 10(9)/L were prospectively enrolled. The evaluable four males and 12 females with a median age of 58 years (range 14-79) included ten patients (63%) previously treated with two or more agents and 12 patients (75%) who had failed other therapies. The median follow-up was seven months (range 15 days to 36 months). RESULTS: Anagrelide, in an average dose of 1.9 mg/day, reduced the platelet count from a mean of 728 x 10(9)/L (95% CI 611-845 x 10(9)/L) to 412 x 10(9)/L (95% CI 319-504 x 10(9)/L) (p < 0.001) and maintained it at this level. Fourteen patients (88%) had a platelet reduction to < 600 x 10(9)/L. All symptomatic patients had improvement in symptoms attributable to thrombocythaemia. There were three haemorrhagic and three thrombotic episodes in a total of three patients (19%), including one death from an intracerebral haemorrhage. Six patients (37%) were removed from therapy due to toxicity after a median of 151 days. Side effects included palpitations, abdominal pain and cough. CONCLUSIONS: Anagrelide is efficacious and safe in ET, both for platelet and symptom control. Minor side effects are common, however, tend to occur early and resolve spontaneously in most cases.

Adolescent↗

An NMR investigation of the conformational effect of nitroxide spin labels on Ala-rich helical peptides.

Nitroxide spin labels, in conjunction with electron spin resonance (ESR) experiments, are extensively employed to probe the structure and dynamics of biomolecules. One of the most ubiquitous spin labeling reagents is the methanethiosulfonate spin label which attaches a spin label selectively to Cys residues via a disulfide bond (Cys-SL). However, the actual effect of the nitroxide spin label upon the conformation of the peptide or protein cannot be unambiguously determined by ESR. In this study, a series of 16-residue Ala-rich helical peptides was characterized by nuclear magnetic resonance techniques. The C alpha H chemical shift analysis, NOEs, and 3JNH alpha coupling constants for peptides with no Cys, free Cys, and Cys-SL (with the N-O group reduced) were compared. These results indicate that while replacement of an Ala with a Cys residue causes a loss of overall helical structure, the Cys-SL residue is helix supporting, as would be expected for a non-beta-branched aliphatic amino acid. Thus, the Cys-SL residue does not perturb helical structure and, instead, exhibits helix-stabilizing characteristics similar to that found for Ala, Met, and Leu.

Alanine↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗