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Biomedical subjects

R Walsh

Publications and source records attributed to R Walsh.

At least 19 recordsLinked to original sources
PubMed2000

Gas-phase kinetic and mechanistic studies of some interconverting alkylcyclopropene pairs: involvement of dialkylvinylidene intermediates and their quantitative behaviour

The pyrolyses of two isomeric pairs of alkylcyclopropenes, namely 1,3-dimethyl-(15) and 1-ethyl-cyclopropene (16), and 1,3,3-trimethyl-(5) and 1-isopropyl-cyclopropene (17), have been studied in the gas phase. Complete product analyses at various conversions up to 95% were obtained for the decomposition of each compound at five temperatures over a 40 degrees C range. The time-evolution data showed that the isomerisation reactions 15<==>16 and 5<==>17 were occurring. Kinetic modelling of each system allowed the determination of rate constants for these and all other decomposition processes. Tests confirmed that all reactions were unimolecular and homogeneous. Arrhenius parameters are reported for overall reactions and individual product pathways. Further kinetic analysis allowed us to extract the propensities (at 500 K) for 1,3-C-H insertion of the dialkylvinylidene intermediates involved in the rearrangements as follows: k(prim):k(sec): k(tert)= 1:16.5:46.4. Additional experiments with 13C-labelled cyclopropenes yielded alkyl group migration aptitudes for the dialkylvinylidenes (from the pattern of 13C in the alkyne products) as follows: Me:Et:iPr=1:3.1:1.5. Explanations for these trends are given. Another important finding is that of the dramatic rate enhancements for 1,3-diene product formation from the 1-alkylcyclopropenes; this can be explained by either hyperconjugative stabilisation of the vinylcarbene intermediates involved in this pathway, or their differing propensities to 1,2 H-shift. The observed large variations in product distribution amongst these four cyclopropenes is interpreted in terms of these specific effects on individual pathways.

Journal Article↗
PubMed2000

Use of a dual monoclonal solid phase and a polyclonal detector to create an immunoassay for the detection of human cardiac troponin I.

OBJECTIVES: We report the development of a fully automated, random access, chemiluminescent immunoassay, for the detection of human cardiac Troponin I (cTnI) in serum and plasma for use on the ACS:180(R) System. DESIGN AND METHODS: This assay format uses a combination of two monoclonal antibodies covalently coupled to paramagnetic (PMP) particles as a solid phase and an affinity purified polyclonal antibody, specific to the N-terminal domain of cTnI (peptide-3 region) labeled with a chemiluminescent compound as the detector antibody. The assay offers excellent low-end sensitivity and precision. RESULTS: No interferences are observed from by blood components such as HAMA and drugs used in cardiac therapy. Patient samples tested on the ACS:180 cTnI assay showed good correlation with the Stratus cTnI assay (ACS: cTnI = 1. 02*Stratus + 0.05 g/L, r = 0.96, n = 1170). CONCLUSION: Paired with the other ACS:180 cardiac assays, myoglobin and CKMBII, the ACS:180 system now offers an excellent panel of cardiac assay for use in rapid and accurate diagnosis of a myocardial event.

Antibodies, Monoclonal↗
PubMed2000

The search for an integral theory of consciousness.

In summary, Miller has identified one of the key concerns of consciousness research. However, significant contributions to an integral theory of consciousness will need to be more clear and precise and to incorporate the relevant literature on current integral theories. If Miller's future writings do this, they may make the contributions we so desperately need.

Consciousness↗
PubMed1999

Quality of care for patients hospitalized with heart failure at academic medical centers.

BACKGROUND: The purpose of this study was to determine the standard of care provided by academic medical centers for the management of congestive heart failure (CHF). METHODS AND RESULTS: The standard of care was estimated by assessing adherence to the treatment guidelines published by the US Agency for Health Care Policy and Research among 522 patients hospitalized at 7 university hospitals with a diagnosis of CHF. Data were abstracted by retrospective chart review. Of the 522 patients analyzed, 435 (83%) had a left ventricular ejection fraction (LVEF) measured or documented. Among these patients, 192 were considered "ideal" candidates for angiotensin-converting enzyme (ACE) inhibitor therapy (ie, with systolic dysfunction [LVEF <40%] and no contraindications to ACE inhibitors). In this cohort of "ideal" candidates, 138 (72%) were receiving ACE inhibitors at hospital discharge, including 60 (44%) who were prescribed doses recommended in large clinical trials. Compliance with patient education guidelines was assessed in all 487 patients who were alive at the time of discharge. Of these patients, 365 (75%) received dietary counseling, 404 (83%) were educated about exercise, 54 (11%) were instructed to follow daily weights, and 468 (96%) were counseled regarding medication compliance. Among the 87 smokers who were alive at time of discharge, 8 (9%) had documented advice to quit smoking. CONCLUSIONS: This study indicates that academic medical centers performed fairly well on the assessment of LVEF, the prescription of ACE inhibitors at discharge, and on education regarding diet, exercise, and compliance with medications. However, the results suggest opportunities for improvement in ACE inhibitor dosing and patient education regarding the importance of monitoring daily weights and smoking cessation.

Academic Medical Centers↗
PubMed1999

The sleep of older people in hospital and nursing homes.

Disturbed sleep can affect personal wellbeing and impede the rehabilitation and recovery of older people from illness. This paper reports the findings of a pilot study which included examination of sleep quality and sleep patterns of older people in community hospital and nursing home settings. A marked proportion of older people reported sleeping well in nursing care settings, and those in nursing homes slept better than those in the community hospital. The main causes of sleep disturbance in both settings were: needing to go to the toilet, noise, pain, and discomfort; a similar pattern was seen across the different settings. No discernible difference was found in quality of sleep and whether patients felt rested or not between those patients on hypnotic medication and those who were not. The implications of the findings for practice and future research are discussed.

Aged↗
PubMed1999

Sonography of solid breast lesions: observer variability of lesion description and assessment.

OBJECTIVE: The purpose of this study was to measure the level of inter- and intraobserver agreement and to evaluate the causes of variability in radiologists' descriptions and assessments of sonograms of solid breast masses. MATERIALS AND METHODS: Sixty sonograms of solid masses were evaluated independently by five radiologists. Observers used the lexicon of a recently published benchmark report on sonographic appearances of breast masses to determine mass shape, margin, echogenicity, echo texture, presence of echogenic pseudocapsule, and acoustic transmission. Final diagnostic assessments were determined by applying the rule-based model of the same benchmark report to the radiologists' descriptions. In addition, one observer interpreted each case twice to evaluate intraobserver variability. Inter- and intraobserver variability were measured using Cohen's kappa statistic. We also investigated causes of variability in radiologists' descriptions. RESULTS: Interobserver agreement ranged from lowest for determining the presence of an echogenic pseudocapsule (kappa = .09) to highest for determining mass shape (kappa = .8). Intraobserver agreement was lowest for mass echo texture (kappa = .24) and greatest for mass shape (kappa = .79). Variability in descriptions of lesions contributed to interobserver (kappa = .51) and some intraobserver (kappa = .66) inconsistency in assessing the likelihood of malignancy. CONCLUSION: Lack of uniformity among observers' use of descriptive terms for solid breast masses resulted in inconsistent diagnoses. The need for improved definitions and additional illustrative examples could be addressed by developing a standardized lexicon similar to that of the Breast Imaging Reporting and Data System.

Adolescent↗
PubMed1999

Scrotal (Bianchi) approach to patent processus vaginalis in children.

Ligation of an indirect inguinal hernia or communicating hydrocele is the most frequent operation performed on children by pediatric surgeons and urologists. We describe our experience with the scrotal (Bianchi) approach to these problems rather than the traditional inguinal approach.

Adolescent↗
PubMed1998

Selective endothelin A receptor antagonists. 4. Discovery and structure-activity relationships of stilbene acid and alcohol derivatives.

This publication describes the synthesis and optimization of a novel series of stilbene endothelin antagonists. Analysis of the SAR established for previous papers in this series prompted the design and synthesis of (Z)-4-phenyl-5-(3-benzyloxyphenyl)pent-4-enoic acid 3 which was found to be a moderately active inhibitor of the binding of [125I]ET-1 to ETA receptors with an IC50 of 6 microM. More interestingly, the intermediate compound (E)-2-phenyl-3-(3-benzyloxyphenyl)propenoic acid 5 was equiactive with 3. Optimization of 5 resulted in the preparation of (E)-2-phenyl-3-(2-cyano-5-(thien-3-ylmethoxy))phenylprope noic acid 18 (RPR111723) which had an IC50 in the binding assay of 80 nM on the ETA receptor and a pKB of 6.5 in the functional assay, measured on rat aortic strips. Reduction of the acid group of 5 gave the first nonacidic ETA antagonist in our series, (E)-2-phenyl-3-(3-benzyloxyphenoxy)prop2-enol 6 with an IC50 of 20 microM. Optimization of 6 resulted in the preparation of 2-(2-methylphenyl)-3-(2-cyano-5-(thien-3-ylmethyl)phenyl)pro p-2-enol 33 with an IC50 of 300 nM on the ETA receptor.

Animals↗
PubMed1998

Characterisation of the effects of robustoxin, the lethal neurotoxin from the Sydney funnel-web spider Atrax robustus, on sodium channel activation and inactivation.

The present study investigates the actions of robustoxin (atracotoxin-Ar1) purified from the venom of the male Sydney funnel-web spider Atrax robustus on sodium channel gating. Using whole-cell patch-clamp techniques the study assessed the actions of robustoxin on tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) sodium currents in rat dorsal root ganglion cells. Similar to the closely related funnel-web spider toxin versutoxin (delta-atracotoxin-Hv1) from Hadronyche versuta, robustoxin had no effect on TTX-R sodium currents but exerted potent effects on TTX-S sodium currents. The main action of robustoxin was a concentration-dependent slowing or removal of TTX-S sodium current inactivation. This steady-state current was maintained during long-lasting depolarisations at all test potentials. Robustoxin (30 nM) also caused a 13-mV hyperpolarising shift in the voltage midpoint of steady-state sodium channel inactivation (h infinity) leading to a reduced peak current at a holding potential of -80 mV. Moreover there was a steady-state or non-inactivating component present (18% of maximal sodium current) at prepulse potentials that normally inactivate all TTX-S sodium channels (more depolarised than -40 mV). In addition robustoxin produced a significant increase in the repriming kinetics of the sodium channel when channels returned to the resting state following activation. This increase in the rate of recovery of sodium current appears to explain the use-dependent effects on peak sodium current amplitude at high stimulation frequencies. Finally 30 nM robustoxin caused an 11-mV hyperpolarising shift in the voltage dependence of the channel but did not markedly modify tail current kinetics. These actions suggest that robustoxin inhibits conversion of the open state to the inactivated state of TTX-S sodium channels, thus allowing a fraction of the sodium current to remain at membrane potentials at which inactivation is normally complete. Given the recent reclassification of funnel-web spider toxins as atracotoxins, robustoxin should henceforth be known as delta-atracotoxin-Ar1 to reflect this main action on sodium channel inactivation. These present results further support the hypothesis that funnel-web spider toxins interact with neurotoxin receptor site 3 to slow channel inactivation in a manner similar to that of alpha-scorpion and sea anemone toxins.

Amino Acid Sequence↗
PubMed1998

The manufacturing process for recombinant factor IX.

Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance the capacity of cells to remove the amino-terminal propeptide from rFIX) into Chinese hamster ovary cells; (2) selection of a cell line that was capable of expressing high amounts of active rFIX while growing in bioreactors containing a completely defined culture medium that does not contain blood or plasma products; and (3) inclusion of four independent chromatography steps, none of which require monoclonal antibodies. Furthermore, rFIX has been extensively tested to demonstrate similarity to plasma-derived factor IX and has been shown to be a consistent, high-purity product. For example, a high-specific-activity product (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and high-purity source of factor IX treatment for patients with hemophilia B.

Animals↗
PubMed1997

Feasibility study of magnetic resonance imaging-guided intranasal flexible microendoscopy.

Interventional magnetic resonance imaging (MRI) offers potential advantages over conventional interventional modalities such as X-ray fluoroscopy, ultrasonography, and computed tomography (CT). In particular, it does not use ionizing radiation, can provide high-quality images, and allows acquisition of oblique sections. We have carried out a feasibility study on the use of interventional MRI to track a flexible microendoscope in the paranasal sinuses. In this cadaver study, high-speed MRI was used to track a passive marker attached to the end of the endoscope. Automatic image registration algorithms were used to transfer the coordinates of the endoscope tip into the preoperative MRI and CT images, enabling us to display the position of the endoscope in reformatted orthogonal views or in a rendered view of the preoperative images. The endoscope video images were digitized and could be displayed alongside an approximately aligned, rendered preoperative image. Intraoperative display was provided in the scanner room by means of an liquid crystal display (LCD) projector. We estimate the accuracy of the endoscope tracking to be approximately 2 mm.

Algorithms↗
PubMed1997

Axillary lymph nodes: mammographic, pathologic, and clinical correlation.

OBJECTIVE: The purpose of this study was to determine the cause and frequency of axillary abnormalities seen mammographically and to evaluate the imaging characteristics of lymphadenopathy that are associated with malignancy. MATERIALS AND METHODS: Ninety-six axillary abnormalities seen mammographically in 94 patients were retrospectively reviewed and correlated with the clinical diagnoses and pathologic results found in the medical records. For each abnormality, the length, margins, and presence of microcalcifications were noted. Logistic regression was used to determine an association between these findings and status (benign or malignant). RESULTS: Seventy-six of 94 patients had lymphadenopathy. Eighteen of 94 patients had an abnormality other than lymphadenopathy. Because two of these 94 patients had more than one abnormality, a total of 96 abnormalities occurred, 20 of which were due to an abnormality other than lymphadenopathy. Regarding the 76 cases of lymphadenopathy, the most frequent diagnosis was nonspecific benign lymphadenopathy in 29% (n = 22) of cases, followed by metastatic breast cancer in 26% (n = 20) and chronic lymphocytic leukemia or well-differentiated lymphocytic lymphoma in 17% (n = 13). Other causes (n = 21) included collagen vascular disease, lymphomas other than well-differentiated lymphocytic lymphoma, metastatic disease from nonbreast primary site, metastatic disease from unknown primary site, sarcoidosis. HIV-related lymphadenopathy, and reactive lymphadenopathy associated with a breast abscess. An association between length of nonfatty lymph nodes and malignant status was statistically significant at the .001 level. When a length greater than 33 mm was used as a predictor of malignancy, the specificity and sensitivity were 97% and 31%, respectively. We found an association between malignancy and nonfatty lymph nodes with ill-defined or spiculated margins (p = .053). Regarding the 20 abnormalities other than lymphadenopathy, epidermal cysts (n = 7) were most prevalent. CONCLUSION: The most common axillary abnormality revealed on mammography was abnormal lymph nodes. Homogeneously dense (nonfatty) axillary lymph nodes were strongly associated with malignancy when the lymph nodes were longer than 33 mm, had ill-defined or spiculated margins, or contained intranodal microcalcifications. However, our study confirmed that in most cases benign and malignant lymph nodes cannot be distinguished from each other mammographically.

Aged↗
PubMed1996

Palatal trauma: an unusual cause of a parotid sinus.

A case is described of a 3-year-old boy who presented with a seemingly trivial injury to his soft palate, who went on to develop a parotid sinus as a result of a retained foreign body. This is a rare clinical problem and it highlights the difficulty in the clinical assessment of a palatal injury--especially in children. The child had the foreign body removed successfully 5 months after the initial injury and made an uneventful recovery.

Child, Preschool↗
PubMed1996

Training medical students in HIV/AIDS test counselling: results of a randomized trial.

The study assessed the effectiveness of a programme aimed at increasing medical students' skills in counselling patients presenting for HIV testing/AIDS information. Senior medical students were randomly assigned to receive a short course in pre- and post-test counselling, or to a control group which received the usual curriculum. The students' performance in counselling simulated patients was videotaped at baseline and after 3 months. A subsample was also assessed at 12 months. Students receiving the programme showed significantly greater improvement in pre- and post-test counselling skills over 3 months than did the controls. For the sub-sample continuing to 12 months, a significant effect over time was found; however, there was no significant difference between the groups. This may have been influenced by the small sample sizes used for the 12-month assessment. General interactional skills improved for the over-all sample over 3 and 12 months, but again there were no significant differences between groups. Those exposed to the programme did not show significantly greater changes in either knowledge or attitude scores over either time frame, compared with controls. When taught in addition to the usual undergraduate curriculum at Newcastle University, this short interactional skills course significantly enhanced students' ability to provide pre- or post-test counselling for HIV/AIDS.

AIDS Serodiagnosis↗