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Biomedical subjects

R Butcher

Publications and source records attributed to R Butcher.

At least 19 recordsLinked to original sources
PubMed1999

Synthesis, characterization and anticonvulsant activity of enaminones. Part 6: Synthesis of substituted vinylic benzamides as potential anticonvulsants.

A comparison of enaminones from various unsubstituted and p-substituted benzamides to the analogous benzylamines has been undertaken with the aim of elucidating the essential structural parameters necessary for anticonvulsant activity. Initial studies on methyl 4-N-(benzylamino)-6-methyl-2-oxocyclohex-3-en-1-oate, 3a, 3-N-(benzylamino)cyclohex-2-en-1-one, 3p, and 5,5-dimethyl-3-N-(benzylamino)-cyclohex-2-en-1-one, 3r indicated that benzylamines possessed significant anti-maximal electroshock seizure (MES) activity. Evaluation of the analogous benzamides revealed significant differences in anticonvulsant activity, these differences were most probably related to the differences in their three-dimensional structures.

Animals↗
PubMed1999

Novel super-high affinity sheep monoclonal antibodies against CEA bind colon and lung adenocarcinoma.

We have developed technology to create monoclonal antibodies (MAbs) using lymphocytes from immunized sheep. The affinities of these sheep monoclonal antibodies (SMA) can be several orders of magnitude higher than mouse MAbs. This paper reports the development and validation of a modified enzyme-linked immunoadsorbent assay (ELISA) method to select high-affinity antibodies of the desired specificity at the first screen. Using this method, we have isolated high affinity SMA to carcinoembryonic antigen (CEA), a marker of colon cancer. Comparisons of our novel SMA with mouse MAbs using the new ELISA and BIAcore technology (BIAcore AB, Stevenage, Herts, UK) have confirmed that we have made super-high affinity antibodies to CEA. One of these has a t(1/2) for dissociation of 8 days, which could provide a longer therapeutic window than is available with murine monoclonals currently being used in the clinic. This antibody has a specific tissue staining profile; it thus appears to be an excellent candidate for use in the clinic.

Adenocarcinoma↗
PubMed1998

Cytokine-induced transcription of protein-tyrosine-phosphatases in human astrocytoma cells.

Interleukin-1 (IL-1) and Tumor Necrosis Factor-a (TNFalpha) are potent mediators of inflammatory reactions in the brain. Although much is known about the effects of IL-1 on expression of secretory proteins, few studies have addressed the question of a selective, IL-1-dependent expression of genes involved in neuromodulatory effects of inflammation. Protein-tyrosine-phosphatases (PTP's) have been shown to regulate signal transduction and adhesion processes in the developing nervous system. They are candidates for inflammation-induced neuromodulation. Therefore, we investigated if IL-1 regulates expression of PTP's. We applied a DNA-fingerprinting method based on the PCR-amplification of conserved domains of gene families and observed IL-1-dependent induction of two PTP's, cytoplasmic PTPvarepsilon and receptor-PTPgamma, RPTPgamma, in human U373-MG astrocytoma cells. Using Northern blot analysis, we confirmed this result and also show that in addition to IL-1, TNFalpha but not IL-6 induces the transcription of cytoplasmic PTPvarepsilon and RPTPgamma in human astrocytoma cells. Given the important role for PTP's in neuromodulatory aspects such as axonal guidance and neurite outgrowth, cytokine-induced induction of PTP's may play an important pathenogenic role in the development of chronic inflammatory diseases in the brain.

Astrocytoma↗
PubMed1998

Synthesis, characterization, and anticonvulsant activity of enaminones. Part 5: investigations on 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothizin-4[10H]-one derivatives.

A new series of anticonvulsant 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-on es is herein reported. 2-Aminothiophenols underwent cyclocondensation with 4-carboalkoxy-5-methylcyclohexane-1,3-diones in refluxing dimethylsulfoxide (DMSO) to yield 3-carboalkoxy-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-on es, 4ak. In the case of the carbo-tert-butoxy derivatives (4c and 4k) prolonged reaction times led to the isolation of the respective 3-unsubstituted-2-methyl-2,3-dihydro-1H-phenothiazin-4[10H]-ones (41 and 4m) instead. Significant anticonvulsant activity was displayed by these analogues, most particularly 4k, which was active at 30 mg/kg intraperitoneally (ip) in mice in the maximal electroshock seizure (MES) evaluation, with no toxicity noted at dosages up to 300 mg/kg. Oral (p.o.) rat evaluation of 4k in the MES evaluation provided an ED50 of 17.60 mg/kg, with no toxicity noted at dosages up to 500 mg/kg, providing a protective index (PI = TD50/ED50) > 28.40. These compounds represent the first reported series of phenothiazines which possess anticonvulsant activity.

Animals↗
PubMed1998

Study to validate the outcome goal, competencies and educational objectives for use in intensive care orientation programs.

Intensive care orientation programs have become an accepted component of intensive care education. To date, however, there have been no Australian-based standards defining the appropriate level of competence to be attained upon completion of orientation. The aim of this study was to validate a set of aims, competencies and educational objectives that could form the basis of intensive care orientation and which would ensure an outcome standard of safe and effective practice. An initial document containing a statement of the desired outcome goal, six competency statements and 182 educational objectives was developed through a review of the orientation programs developed by the investigators. The Delphi technique was used to gain consensus among 13 nurses recognised for their expertise in intensive care education. The expert group rated the acceptability of each of the study items and provided suggestions for objectives to be included. An approval rating of 80 per cent was required to retain each of the study items, with the document refined through three Delphi rounds. The final document contains a validated statement of outcome goal, competencies and educational objectives for intensive care orientation programs.

Australia↗
PubMed1996

A protective anti-peptide antibody against the immunodominant site of the A24 Cruzeiro strain of foot-and-mouth disease virus and its reactivity with other subtype viruses containing the same minimum binding sequence.

A synthetic peptide vaccine of the general sequence Cys-Cys-(200-213)-Pro-Pro-Ser-(l41-158)-Pro-Cys-Gly(peptide A40), where the numbered residues refer to the VP1 sequence of foot-and-mouth disease virus (FMDV) strain A24 Cruzeiro, has previously been shown to elicit neutralizing and protective antibodies in guinea-pigs and cattle. To examine this immunogenic tract in more detail monoclonal antibodies (MAbs) were raised to this peptide. One such MAb C1.1, which recognized the homologous peptide, bound to native virus, neutralized infectivity in vitro and passively protected mice from challenge. Using overlapping dodecameric peptides the minimum binding 'footprint' of this MAb incorporated residues 149-154 which were respectively Gly-Ser-Leu-Ala-Ala-Arg. Since this 'footprint' occurs in several other A subtype strains of FMDV, the extent to which MAb C1.1 could cross-react was also examined. Using a liquid-phase competition ELISA, only viruses with a sequence that encompassed the same minimum binding 'footprint', namely A27 Cundinamarca Colombia/76, A Argentina/79, and A Venceslau Brazil/76 reacted with similar affinity against MAb C1.1. However, further serological examination of C1.1 with these viruses by indirect ELISA, in vitro neutralization and passive protection showed clear functional disparity. In contrast to the liquid-phase ELISA, the ability of C1.1 to react with electrostatically bound virus varied significantly depending on the subtype examined. Moreover, the capacity of this MAb to neutralize these subtypes showed wide divergence which was mirrored by the protection data.

Amino Acid Sequence↗
PubMed1996

Definition and management of anxiety, agitation, and confusion in ICUs.

Critically ill patients require continuous assessment of their need for sedation and pain management. The purpose of this study was to develop a consistent categorization of patient's symptoms and to identify actions that yield effective patient outcomes. Nurses in this study described patients with sedation problems as those who were disoriented or aggressively acting out, fearful and restless, or manifesting changes in orientation, memory loss, or mental status. Twenty-seven medical intensive care unit (MICU) nurses volunteered to complete a questionnaire about their assessment process in determining patient's sedation needs, interventions, and evaluation criteria for patient outcomes. Fifty-five patient questionnaires were completed by the nurses. Nurses identified separate subjective and objective cues for patients' anxiety, agitation, and confusion. The most frequently identified nursing actions were assessment to differentiate between pain, anxiety, agitation, and confusion; personal reassurances, relaxation and other physical comfort techniques; administer prescribed medication; collaborate with a physician to identify cause; and give additional prescribed medication. Effective outcome measures included stable vital signs, normal oxygen saturation, progression with ventilator weaning if appropriate, return to normal level of orientation, and a quiet yet arousable state.

Adult↗
PubMed1995

The development of the Australian Basic Intensive Care Knowledge Test.

The Basic knowledge Assessment Tool (BKAT), a test developed in the United States, has been presented as a valid and reliable test of basic knowledge for critical care nursing. However, it was necessary to determine the BKAT's validity and reliability in the Australian intensive care (IC) context. The Delphi technique, utilising a panel of eleven experts, was used to determine the content validity of the BKAT. The Delphi process resulted in the development of a test with 105 questions. These questions consist of 49 original BKAT questions, 25 original BKAT questions slightly modified, 3 original BKAT questions with major modifications and 28 new questions. A criterion group design was used to establish the modified test's reliability and decision validity. Item analysis was undertaken using item difficulty and item discrimination indexes. The modified test was completed by 14 registered nurses with no IC experience, 18 registered nurses with intermediate IC experience and 25 registered nurses qualified as intensive care specialists. The mean score (and standard deviation) for the test for each of the respective groups was 41(9), 69(9) and 86(7). These results were significantly different (p < 0001). The reliability was established with a Cronbach Alpha coefficient of .96. The modified test is a reliable and valid measure of IC basic knowledge and can be used as a valuable adjunct in the assessment of IC orientation programs.

Australia↗
PubMed1994

African-American physicians' views on health reform: results of a survey.

Little is known about African-American physicians' health system experience or their opinions on health reform. In an attempt to obtain socioculturally relevant data quantifying these experiences and opinions, the National Medical Association administered a 38-question, 80-item survey instrument in August 1993. The questionnaire was completed by 236 physicians. The results indicate that African-American physicians feel health care is a right and that the health system needs fundamental change. Although there was no consensus on the type of health reform needed, approximately 35% cited availability and access to care to be the greatest problem facing the system with high costs of care (18.2%) ranking second. Unique findings in the survey indicated respondents felt that the needs and concerns of most African Americans will not be fairly addressed in the reform of the health-care system, that African-African physicians are not included in the formation of health-care policies, and that African-American physicians are facing high levels of professional and healthcare system racial discrimination. More than 99% of African-American physicians reported some degree of racial discrimination in the practice of medicine including peer review, obtaining practice privileges at hospitals, hospital staff promotions, Medicaid and Medicare reimbursements, malpractice suits, private insurance oversight and reimbursements, and referral practices of white colleagues. These findings have profound health policy, health financing, and health service delivery implications and should be included in debates and deliberations on health reform.

Adult↗
PubMed1993

Characterization of monoclonal antibodies against a type SAT 2 foot-and-mouth disease virus.

This paper is the first to describe characterization of monoclonal antibodies (MAbs) against a South African Territories 2 (SAT 2) foot-and-mouth disease virus (isolate Rho 1/48). Twelve MAbs which neutralized homologous virus were characterized in indirect and sandwich ELISA using purified Rho 1/48 virus particles, subunits, trypsin-treated, and chemically denatured virus. All the MAbs inhibited haemagglutination by parental virus. Binding of the MAbs to 73 SAT 2 field isolates was measured in a sandwich ELISA and defined four distinct antigenic regions. Preliminary characterization of escape mutants selected with some of the MAbs using virus neutralization tests, ELISA, and amino acid sequencing is included. MAbs 2, 25, 40, 48 and 64, reacted with a linear epitope on the VP1 loop region. An amino acid change at position 149 (valine to glutamic acid) was detected in mutants selected by MAb 2 and 40 and this eliminated binding and neutralization by all the other MAb. This epitope was conformation-dependent and was conserved in all 73 isolates of SAT 2 examined. Escape mutants isolated with MAb 41 and 44, had changes at positions 156 (glycine to aspartic acid), or 158 (serine to leucine) respectively. These MAbs bound with Rho 1/48 only out of 73 field strain viruses studies and the reactions of MAbs from the other groups was unaltered. MAb 27, 28 and 37 reacted with a conformation-dependent epitope on VP1 which was not conserved in field isolates. All mutants selected by these MAbs had a single amino acid substitution at position 149 (valine to alanine). The same change was always found in field isolates which did not bind MAbs from this group. MAb 11 reacted with a linear epitope associated with amino acids 147 or 148 on VP1 and showed similar binding characteristics to a conformation dependent MAb 7, no amino acid residue changes were found within VP1 for monoclonal antibody 7 mutants.

Amino Acid Sequence↗
PubMed1986

Optimisation of indices of external pneumatic compression for prophylaxis against deep vein thrombosis: radionuclide gated imaging studies.

The amount and rate of blood expelled with different modes of intermittent external pneumatic compression applied to the lower leg were studied on a regional basis in a series of experiments on healthy human volunteers. Radionuclide imaging of the labelled blood pool, with acquisition of counts synchronised to the pressurisation cycle, provided data on regional blood volumes in the leg in relation to time. To determine the changes in blood volume of the lower leg resulting from external pneumatic compression labelled red blood cell counts were determined during 10 different types of compression cycle. Since venous stasis is considered to be a major cause of venous thrombosis the red blood cell counts were used to calculate regional values of the fraction of blood ejected as well as comparative indices proportional to regional flow rate, regional velocity, and regional wall shear stress. All these indices should be maximised for optimal prophylaxis against deep vein thrombosis. The four compartment cuff in each compression mode applied a mean pressure of 45 mm Hg, but different combinations of values were used for intercompartmental pressure gradation (delta p) and for intercompartmental time sequencing to the onset of compression (delta t). Uniform compression (delta p = 0; delta t = 0) was substantially inferior to cycles with gradation and sequencing. The optimal values of delta p were in the range 5-10 mm Hg and of delta t in the range 0-0.5 seconds.

Adolescent↗
PubMed1982

Monoclonal antibodies against foot-and-mouth disease virus 146S and 12S particles.

This paper is the first description of monoclonal antibodies specific for foot-and-mouth disease virus (FMDV). Using these antibodies, it was possible to distinguish similar and unique antigenic sites on complete (146S) or subunit (12S) virus particles. Some of these monoclonal antibodies could also distinguish between 12S subunits made by acid degradation of 146S virus (12SA) and those viral components found in infected cell lysates which sediment in sucrose density gradients as "12S subunits" (12SN).

Animals↗