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Biomedical subjects

P Marshall

Publications and source records attributed to P Marshall.

At least 19 recordsLinked to original sources
PubMed2006

The relaxation of OH (v=1) and OD (v=1) by H2O and D2O at temperatures from 251 to 390 K.

We report rate coefficients for the relaxation of OH(v=1) and OD(v=1) by H2O and D2O as a function of temperature between 251 and 390 K. All four rate coefficients exhibit a negative dependence on temperature. In Arrhenius form, the rate coefficients for relaxation (in units of 10(-12) cm3 molecule-1 s-1) can be expressed as: for OH(v=1)+H2O between 263 and 390 K: k=(2.4+/-0.9) exp((460+/-115)/T); for OH(v=1)+D2O between 256 and 371 K: k=(0.49+/-0.16) exp((610+/-90)/T); for OD(v=1)+H2O between 251 and 371 K: k=(0.92+/-0.16) exp((485+/-48)/T); for OD(v=1)+D2O between 253 and 366 K: k=(2.57+/-0.09) exp((342+/-10)/T). Rate coefficients at (297+/-1 K) are also reported for the relaxation of OH(v=2) by D2O and the relaxation of OD(v=2) by H2O and D2O. The results are discussed in terms of a mechanism involving the formation of hydrogen-bonded complexes in which intramolecular vibrational energy redistribution can occur at rates competitive with re-dissociation to the initial collision partners in their original vibrational states. New ab initio calculations on the H2O-HO system have been performed which, inter alia, yield vibrational frequencies for all four complexes: H2O-HO, D2O-HO, H2O-DO and D2O-DO. These data are then employed, adapting a formalism due to Troe (J. Troe, J. Chem. Phys., 1977, 66, 4758), in order to estimate the rates of intramolecular energy transfer from the OH (OD) vibration to other modes in the complexes in order to explain the measured relaxation rates-assuming that relaxation proceeds via the hydrogen-bonded complexes.

Journal Article↗
PubMed2005

Casting versus surgical fixation for grade IIIA open tibial diaphysial fractures in children: effect on the rate of infection and the need for secondary surgical procedures to promote bone union.

We evaluated 39 grade IIIA open tibial fractures presenting in children younger than 13 years of age, to determine if the mode of fracture stabilization (casting vs. surgical fixation) was related to the rate of infection or the need for secondary surgical procedures to promote bone union. All fractures had wound debridement in the operating room. Thirty patients had manipulation and casting, and nine surgical internal or external fixation. There were two cases of infection in the cast-treated group and two in the surgical fixation group (P=0.17). None of the fractures required a secondary surgical procedure to promote bone union. Three of the fractures treated by manipulation and casting displaced; two required re-manipulation and casting and one was converted to external fixation. In two cases the applied external fixator had to be re-aligned. Our results suggest that manipulation and casting is a reliable treatment for open tibial fractures in children.

Adolescent↗
PubMed2005

Caesarean section in a patient with cystic fibrosis.

Severely impaired pulmonary function due to cystic fibrosis is associated with a poor pregnancy outcome. A 19-year-old primigravida with cystic fibrosis had a forced expiratory volume in one second 34% of predicted and a low body mass index of 17.1 kg/m(2) before pregnancy. During pregnancy she required several admissions to hospital for deteriorating pulmonary function due to infection. She also developed gestational diabetes and required overnight feeding via a gastrostomy tube throughout pregnancy to improve her nutritional status. With close medical attention, pulmonary function tests remained stable. A joint decision was made to deliver the baby by caesarean section at 33 weeks' gestation as this was considered optimal time for mother and baby and to avoid potential catastrophic pulmonary deterioration later in pregnancy. A combined spinal-epidural technique provided adequate anaesthesia. Pulmonary function tests were performed in theatre before and after the spinal injection, as well as two and five hours postoperatively. Despite a spinal anaesthetic block to T5 bilaterally, lung function tests remained stable. An epidural infusion provided good postoperative analgesia. The outcome was successful for mother and fetus.

Adult↗
PubMed2003

Climate change, human impacts, and the resilience of coral reefs.

The diversity, frequency, and scale of human impacts on coral reefs are increasing to the extent that reefs are threatened globally. Projected increases in carbon dioxide and temperature over the next 50 years exceed the conditions under which coral reefs have flourished over the past half-million years. However, reefs will change rather than disappear entirely, with some species already showing far greater tolerance to climate change and coral bleaching than others. International integration of management strategies that support reef resilience need to be vigorously implemented, and complemented by strong policy decisions to reduce the rate of global warming.

Adaptation, Biological↗
PubMed2003

Does balloon mitral valvuloplasty improve cardiac function? A mechanistic investigation into impact on exercise capacity.

Procedural technical success of balloon mitral valvuloplasty (BMV) is indicated by an increase in valve area and a reduction in transvalvar gradient, but there are conflicting results regarding whether these indicators correlate with subsequent improvements in exercise capacity. We conducted a study to explore the effects of valvuloplasty on cardiac function to gain insight into the mechanisms responsible for the impact on exercise ability. Sixteen patients with mitral stenosis participated in the study and the five who did not proceed to valvuloplasty served as the control group. All patients performed maximal cardiopulmonary exercise tests before and 6 weeks after valvuloplasty (without valvuloplasty in controls). Central haemodynamics including cardiac output were measured non-invasively at rest and peak exercise. At baseline, the cardiopulmonary exercise test results were similar in the two groups. Following valvuloplasty, cardiac output did not alter at rest, but increased significantly at peak exercise (8.7+/-1.7 to 10.5+/-2.1 l min(-1), P<0.01), as did peak cardiac power output (1.88+/-0.55 to 2.28+/-0.74, P<0.05) and cardiac reserve (1.07+/-0.33 to 1.45+/-0.55 watts, P<0.05). Aerobic exercise capacity improved (13.9+/-4.2 to 16.4+/-4.3 ml kg(-1) min(-1), P<0.01) as did exercise duration (354+/-270 to 500+/-266 s, P<0.01). There were no significant changes in the controls. There was a significant correlation between the changes in peak VO(2) and changes in cardiac reserve (r=0.62, P<0.01) but not with changes in resting haemodynamics. These changes did not correlate with changes in peri-procedural mitral valve haemodynamics, despite increases in mitral valve area from 1.05+/-0.16 to 1.74+/-0.4 cm(2) (P<0.0001), accompanied by falls in the transvalvar gradient and pulmonary artery pressure (12.4+/-4.7 to 4.5+/-3 mmHg, and 26.8+/-8.4 to 17.4+/-5.2 mmHg, respectively, all P<0.0001). In conclusion, we found that successful mitral valvuloplasty in our patient cohort led to improved cardiac and physical functional capacity but not resting haemodynamics. Neither indicators of technical success nor resting haemodynamics were very reliable in predicting functional improvement.

Adult↗
PubMed2003

The validity and reliability of surface EMG to assess the neuromuscular response of the abdominal muscles to rapid limb movement.

The transversus abdominus muscle (TrA) has been demonstrated to be active prior to rapid movements of the upper and lower limbs. This activity is termed feed forward motivation. The lack of feed-forward activation for TrA has been demonstrated in subjects with low back pain. The measures used for investigation of TrA function have been fine-wire needle EMG. This limits the practical application of TrA study due to the cost and level of specialisation required for this technique. The objective of the current study was to investigate the validity and reliability of using a surface EMG site to replicate the findings for the feed-forward activation of TrA prior to rapid limb movement. A population of healthy, young males (n = 20) were studied and it was found that four of the subjects did not meet feed-forward criteria. These results were shown to be highly reliable after a 2-week period for the TrA/IO site only. The validity of the signal was further investigated using several functional tasks to specifically target muscles of the abdominal region. Using a cross-correlation analysis to evaluate crosstalk from adjacent muscles, it was concluded that the signal representing TrA/IO accurately demonstrates the functional activity of the muscle. This study has demonstrated a viable surface EMG method to evaluate the feed-forward activation of TrA/IO prior to rapid limb movement. This may lead to opportunities for the clinical application of this method. It was also a finding of this study that four asymptomatic subjects did not pre-activate, therefore providing a rationale for future prospective investigations on whether the lack of TrA/IO feed-forward activation is a cause or an effect of low back pain.

Abdominal Muscles↗
PubMed2003

Ultrasound grading of cerebral ventricular dilatation in preterm neonates.

OBJECTIVE: To compare three grading systems previously described for the measurement of cerebral ventricular dilatation in preterm neonates using ultrasound scans and then to compare these with expert clinical judgement. METHODS: Eighty-one preterm neonates <1500 g birthweight or < 32 weeks' gestation, with normal, mild, moderate or severely dilated ventricles recorded predominantly during the first 2 weeks of life were selected to ensure a broad representation of ventricular size. Their cranial ultrasound scans obtained nearest to 6 weeks of age were studied. The ventricular index, the diagonal width in the coronal plane and the ventricular height in the parasagittal plane were measured adjacent to the foramen of Monro and were used to grade the degree of dilatation. In 20 of these neonates, this grading was compared with grading based on expert clinical judgement. RESULTS: Grading according to the ventricular index defined 79% of the scans as normal. However, only 44% and 39% were considered to be normal according to vertical height and diagonal width, respectively. There was a high level of correlation between expert clinical judgement and grading based on ventricular height measurement (r = 0.812; area under receiver operating characteristic (ROC) curve = 0.922) and the diagonal width (r = 0.806; area under ROC curve = 0.935). Ventricular index correlated poorly with clinical judgement (r = 0.298; area under ROC curve = 0.604). CONCLUSIONS: The measurement of ventricular height and the measurement of diagonal width correlated well with expert clinical judgement. The ventricular index correlated poorly and was less sensitive to mild dilatation. There was no correlation between the ventricular index and the other two measures. The ventricular height and the diagonal width are more appropriate for assessing ventricular dilatation in preterm neonates.

Australia↗
PubMed2002

A mechanistic investigation of ACE inhibitor dose effects on aerobic exercise capacity in heart failure patients.

BACKGROUND: Angiotensin converting enzyme inhibitors at high doses have been shown to improve prognosis of heart failure patients. Their beneficial effects on exercise capacity have been less convincing in large parallel group studies. The objective of this investigation was to explore the mechanisms involved in dose-related functional effects and to test the hypothesis that a trial recommended high dose of lisinopril would improve aerobic exercise capacity and cardiovascular function more than with a low dose. METHODS: Twelve patients with symptomatic heart failure completed a randomized double-blind crossover trial of lisinopril 5 mg o.d. and 20 mg o.d. for 24 weeks, crossing over the doses at 12 weeks. The primary end-point was aerobic exercise capacity, and the secondary end-points were cardiac performance at peak exercise and dobutamine stimulation. RESULTS: The aerobic exercise capacity (primary end-point) was significantly higher during the 5mg per day dosage compared to the 20 mg (1696 vs 1578 ml.min(-1), P=0.016), equivalent to a rise of 1.53 ml.kg(-1)min(-1) from the 19.6 ml.kg(-1)min(-1) with 20mg when normalized by body weight. Seventy-three percent of patients showed greater peak oxygen consumption and peak cardiac power output with the 5mg per day dose than the 20 mg, and none showed the opposite. In terms of cardiac performance, although the results were not statistically significant, there was a consistent pattern showing the same directional changes in favour of the lower dose in peak exercise cardiac power output and cardiac power output at maximal dobutamine. There were no significant differences in the resting values. A total of 24 adverse reactions were reported during the 5 mg phase compared to 38 during the 20 mg phase. CONCLUSIONS: Contrary to expectation, the aerobic exercise capacity of patients was found to be greater with the lower dose of lisinopril, suggesting that therapy with ACE inhibitors for heart failure may require tailoring the doses to the individual to optimize functional benefits in relation to the assumed prognostic benefits.

Aged↗
PubMed2001

Newspaper reporting of screening mammography.

BACKGROUND: Continuing controversy surrounds screening mammography, particularly for women 40 to 49 years of age. Newspapers are potentially important sources of information on this topic, but it is not known whether they provide well-founded and objective information and recommendations. OBJECTIVE: To examine how screening mammography is reported in newspapers. DESIGN: Cross-sectional descriptive study. SETTING: 6 top-circulation U.S. newspapers, 1990 to 1997. MEASUREMENTS: Number of articles about screening mammography, issues covered by the articles, information sources, content and sources of quotes, recommendations cited in articles, and presentation of risks and benefits. RESULTS: The most common theme of newspaper articles about mammography was screening for women 40 to 49 years of age. Thirty-one percent of the articles presented information without citing a source or justification. Quotes and recommendations in the articles were approximately twice as likely to support as to express reservations about mammography for women aged 40 to 49 years. Recommendations changed little over time and rarely reflected changes in recommendations of national organizations. Of the 102 articles describing the benefits of mammography, 95% expressed them in relative terms and 11% expressed them in absolute terms. CONCLUSIONS: Newspapers tended to overrepresent support for screening mammography for women aged 40 to 49 years. Reports would have been improved by identification of all sources for information cited, less reliance on relatively few sources, and discussion of benefits in absolute as well as relative terms. Medical journalism may benefit from identification of standards similar to those used for reporting medical research.

Adult↗
PubMed2001

The mouse dystrophin enhancer is regulated by MyoD, E-box-binding factors, and by the serum response factor.

In vivo studies in the mouse have revealed that the muscle promoter of the mouse dystrophin gene can target the right ventricle of the heart only, suggesting the need for other regulatory elements to target the skeletal muscle as well as other compartments of the heart. In this study we report the identification of the mouse dystrophin gene enhancer that is located approximately 8.5 kilobases downstream from the mouse dystrophin gene muscle promoter. The enhancer was tested in myogenic G8, H9-C2, and nonmyogenic 3T3 cell lines and is mostly active in G8 myotubes. Sequence analysis of the mouse dystrophin gene enhancer revealed the presence of four E-boxes numbered E1-E4, a putative mef-2 binding site, and a serum response element. Site-directed mutagenesis studies have shown that E-boxes 1, 2, and 3 as well as the serum response element are required for enhancer activity. Gel shift analysis revealed two binding activities at binding sites E1 and E3 which were specific to myotubes, and supershift assays confirmed that myoD binds at both these sites. Our study also shows that werum response factor binds the serum response element but in myoblasts and fibroblasts only, suggesting that serum response factor may repress enhancer function.

Animals↗
PubMed2001

Single bead characterization using analytical constructs: application to quality control of libraries.

Analytical construct technology has been successfully applied to the single-bead analysis of a split-mix combinatorial library. Substrates can be released from the resin by conventional cleavage for biological screening. Alternatively, for the purpose of analysis and quality control, cleavage at an orthogonal construct linker produces an analytical fragment incorporating the substrate. This analytical fragmnent is highly sensitized to electrospray mass spectrometry (ESI-MS) and is easily identified by isotope labeling. The construct cleavage rendered readily visible even those compounds that clearly could not be seen by conventional cleavage and mass spectrometry analysis. A 1H NMR control experiment proved that the compounds cleaved conventionally were, however, present in the sample in good yield and purity. In view of the data obtained, we think that this is a significant and important step toward solving our current quality control problems.

Amino Acids↗
PubMed2001

Reporter resins for solid-phase chemistry.

[reaction: see text] An analytical construct resin, designed to aid the analysis of solid-phase chemistry, has been mixed in a small proportion with a conventional resin. The analytical construct ("reporter resin") contains two orthogonal linkers that allow cleavage of either the synthetic intermediates (at linker 2) or their analytically enhanced derivatives (at linker 1). The convenient and rapid monitoring of each step in the syntheses of representative library compounds was possible using small resin aliquots.

Chemistry, Pharmaceutical↗
PubMed2001

The ubiquitin-proteasome pathway plays an essential role in proteolysis during Trypanosoma cruzi remodeling.

Here, we document for the first time the presence of the 26S proteasome and the ubiquitin pathway in a protozoan parasite that is in an early branch in the eukaryotic lineage. The 26S proteasome of Trypanosoma cruzi epimastigotes was identified as a high molecular weight complex (1400 kDa) with an ATP-dependent chymotrypsin-like activity against the substrate Suc-LLVY-Amc. This activity was inhibited by proteasome inhibitors and showed same electrophorectic migration pattern as yeast 26S proteasome in nondenaturating gels. About 30 proteins in a range of 25-110 kDa were detected in the purified T. cruzi 26S proteasome. Antibodies raised against the AAA family of ATPases from eukaryotic 26S proteasome and the T. cruzi 20S core specifically recognized components of T. cruzi 26S. To confirm the biological role of 26S in this primitive eukaryotic parasite, we analyzed the participation of the ubiquitin (Ub)-proteasome system in protein degradation during the time of parasite remodeling. Protein turnover in trypomastigotes was proteasome and ATP-dependent and was enhanced during the transformation of the parasites into amastigotes. If 20S proteasome activity is inhibited, ubiquitinated proteins accumulate in the parasites. As expected from the profound morphological changes that occur during transformation, cytoskeletal proteins associated with the flagellum are targets of the ubiquitin-proteasome pathway.

Acetylcysteine↗
PubMed2001

Identification of protein carbonyls after two-dimensional electrophoresis.

The oxidative modification of proteins plays a major role in a number of human diseases, but identity of the specific proteins that are most susceptible to oxidation has posed a difficult problem. Protein carbonyls are increased after oxidative stress, and after derivatization with 2,4-dinitrophenyl hydrazine (DNP) they can be detected by various analytical and immunological methods. Although high resolution two-dimensional electrophoresis (2-DE) can resolve virtually all proteins present in a cell or tissue it has been difficult to determine the oxidized proteins because the DNP-derivatization process alters the isoelectric points of proteins, and additional procedures must be utilized to remove reaction byproducts. These additional procedures can lead to loss of sample, and poor isoelectric resolution on immobilized pH gradient (IPG) strips. We have developed a method that allows the IPG strips to be derivatized with DNP directly following isoelectric focusing of the proteins. This method allows the visualization of oxidized proteins by 2-DE with high reproducibility.

Blood Proteins↗
PubMed2001

Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.

BACKGROUND: Cardiac surgery patients' hematocrits frequently fall to low levels during cardiopulmonary bypass. METHODS: We investigated the association between nadir hematocrit and in-hospital mortality and other adverse outcomes in a consecutive series of 6,980 patients undergoing isolated coronary artery bypass graft surgery. The lowest hematocrit during cardiopulmonary bypass was recorded for each patient. Patients were divided into categories based on their lowest hematocrit. Women had a lower hematocrit during bypass than men but both sexes are represented in each category. RESULTS: After adjustment for preoperative differences in patient and disease characteristics, the lowest hematocrit during cardiopulmonary bypass was significantly associated with increased risk of in-hospital mortality, intra- or postoperative placement of an intraaortic balloon pump and return to cardiopulmonary bypass after attempted separation. Smaller patients and those with a lower preoperative hematocrit are at higher risk of having a low hematocrit during cardiopulmonary bypass. CONCLUSIONS: Female patients and patients with smaller body surface area may be more hemodiluted than larger patients. Minimizing intraoperative anemia may result in improved outcomes for this subgroup of patients.

Aged↗
PubMed2001

Peak exercise cardiac power output; a direct indicator of cardiac function strongly predictive of prognosis in chronic heart failure.

OBJECTIVES: This study assessed the prognostic value of peak cardiac power output, measured non-invasively during maximal cardiopulmonary exercise testing, against other exercise-derived haemodynamic variables in patients with chronic congestive heart failure. METHOD AND RESULTS: Two hundred and nineteen unselected, consecutive patients with congestive heart failure (166 men, mean (+/-SD) age of 56+/-13 years) who underwent maximal symptom limited cardiopulmonary treadmill exercise testing with non-invasive estimation of cardiac output using carbon dioxide re-breathing techniques, were followed-up for a mean period of 4.64 (4.47--4.82, 95% CI) years. Cardiac power output was calculated from the product of cardiac output and mean arterial blood pressure. All cause mortality was 12.3% (27 deaths). Peak and resting cardiac power output, peak mean arterial blood pressure, peak and resting cardiac output and peak VO(2)were all predictive of outcome on univariate analyses. Peak cardiac power output, either entered continuously or categorically with a cut-off value of 1.96 watts, was the only independent predictor of mortality (P=0.0004 for values < or >1.96 watts and P=0.001 for continuous values) using multivariate analysis. A relative risk ratio of 5.08 (1.94-13.3, 95% CI) was obtained for a cardiac power output <1.96 watts. CONCLUSION: Peak cardiac power output is an independent predictor of mortality that can be measured non-invasively using cardiopulmonary exercise testing. It can give further prognostic power to a peak VO(2)in the assessment of patients with congestive heart failure.

Adult↗