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R D Smith

Publications and source records attributed to R D Smith.

At least 235 records · Page 13Linked to original sources
PubMed1993

Decision analysis in the evaluation of diagnostic tests.

Decision analysis was used to evaluate the clinical usefulness of 2 diagnostic tests: one for canine heartworm disease and the other for bovine traumatic reticulo-peritonitis. Several clinically relevant measures of test performance are introduced, including expected utility, risk profile, testing band, threshold analysis, and the relative cost of misdiagnosis. One of the principal benefits of decision analysis of diagnostic tests is that the technique can be used to determine how changes in underlying assumptions will affect clinical decisions. If clinicians can identify and assign values to relevant variables, then decision analysis can provide clinically meaningful guidelines for interpreting the results of diagnostic tests. To take advantage of these techniques, clinicians must become comfortable with quantitative expressions for test performance, risk, and prognosis.

Animals↗
PubMed1993

A cost-utility approach to the use of 5-fluorouracil and levamisole as adjuvant chemotherapy for Dukes' C colonic carcinoma.

OBJECTIVE: To perform an economic evaluation of the joint use of 5-fluorouracil and levamisole as adjuvant chemotherapy in patients with fully resected Dukes' Stage C carcinoma of the colon, compared with resection and no chemotherapy. The evaluation was prompted by a study (N Engl J Med 1990; 322: 352-358) which recommended a new treatment standard for colon cancer: a 52-week course of fluorouracil, with levamisole every second week, as adjuvant chemotherapy. This recommendation raised several concerns, particularly about the quality of life of patients undergoing such a long course of chemotherapy and the costs to the health care system. METHODS: The cost of the surgery plus chemotherapy was estimated and compared with the cost of surgery alone. Descriptions of quality of life were developed from interviews with patients and health professionals, and the time trade off technique was then used to derive utility weights from a small sample (16) which were used to adjust length of life to reflect quality, in terms of a "quality adjusted life year" (QALY). RESULTS: Chemotherapy increases the total cost of treating a patient with colon cancer by $7000, from $6000 to $13,000. Incorporating quality of life reduced the extra benefit gained from the chemotherapy from 2.4 life years to 0.4 QALYs. Thus the result is a cost of $17,500 to achieve an extra QALY from this particular treatment. CONCLUSIONS: The results of this analysis are only tentative, as the quality of life descriptions were not measured over time but from a cross-sectional survey of patients, and the valuations of health states were derived from a small sample. However, we believe them to be indicative, and conclude that it is perhaps more appropriate for the use of chemotherapy to be an option rather than standard treatment until further research on these aspects is complete.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Tandem mass spectrometry of very large molecules. 2. Dissociation of multiply charged proline-containing proteins from electrospray ionization.

Collisional dissociation tandem mass spectra have been obtained for multiply charged molecules produced by electrospray ionization for a variety of proline-containing proteins extending up to 22,000 molecular weight. Interpretation of limited m/z range, low-resolution tandem mass spectra from multiply charged precursors can present difficulties due to the possibility of multiply charged product ions and the lack of unambiguous charge-state information. Methods used to guide the spectral interpretation process under these circumstances are discussed. Proline is a unique amino acid constituent because its side chain is bonded to the tertiary nitrogen in a cyclic pyrrolidine ring. For large polypeptides containing proline residues, we have observed that fragmentation due to cleavage of the amide bond to proline is often dominant. Such proline-directed processes are often the only dissociation pathways observed for large proteins. This is attributed to the quasithermal nature of large molecule collisional activation/dissociation processes and the lower dissociation energies for peptide bonds near proline residues. The present results also suggest possible effects on the dissociation processes for large molecules due to charge location and perhaps protein conformation.

Amino Acid Sequence↗
PubMed1993

Collisionally activated dissociation and tandem mass spectrometry of intact hemoglobin beta-chain variant proteins with electrospray ionization.

Electrospray ionization collisionally activated dissociation (CAD) mass spectra of multiply charged human hemoglobin beta-chain variant proteins (146 amino acid residues, 15.9 kDa), generated in the atmospheric pressure/vacuum interface and in the collision quadrupole of a triple-quadrupole mass spectrometer, are shown and compared. Several series of structurally informative singly and multiply charged b- and y-mode product ions are observed, with cleavage of the Thr 50-Pro 51 CO-NH bond to produce the complementary y96 and b50 sequence ions as the most favored fragmentation pathway. The eight different beta-globin variants studied differ by a single amino acid substitution and can be differentiated from the observed m/z shifts of the assigned product ions. The overall fragmentation patterns for the variant polypeptides are very similar, with the exception of the Willamette form, in which Arg is substituted for Pro- 51, and multiply charged y96 product ions are not observed. Circular dichroism spectra of normal beta A and beta Willamette show very little difference under a variety of solvent conditions, indicating that fragmentation differences in their respective CAD mass spectra are substantially governed by primary rather than secondary structure.

Adult↗
PubMed1993

Direct observation of a DNA quadruplex by electrospray ionization mass spectrometry.

In 10 mM sodium phosphate, pH 7.6, containing 0.1 mM ethylenediaminetetraacetic acid, ions correspondings to the non-calent, four-stranded oligonucleotide, d(CGCG4GCG)4, were detected by negative ion electrospray ionization (ESI) mass spectrometry at a low nozzle-skimmer (delta NS) bias (-150 V), but not at a higher delta NS bias (> -250 V). In contrast, when the sample was desalted and analyzed by ESI mass spectrometry at a low delta NS bias only ions for the single-stranded d(CGCG4GCG) species were observed. These data agree with spectroscopic evidence which showed that oligonucleotides with the sequence motif 5'd(CGCGnGCG)3', where n = 2-5, formed stable four-stranded complexes in the presence of monatomic cations, like K+, Ca2+, Na+ and Li+, but not in their absence.

Base Sequence↗
PubMed1993

Expression of multiple type 1 phosphoprotein phosphatases in Arabidopsis thaliana.

Type 1 phosphoprotein Ser/Thr phosphatases (PP1) are highly conserved enzymes found in all eukaryotes. These enzymes have multiple functions in fungal and animal cells but little is known of their function and regulation in plants. Previous studies in our laboratory indicated that maize and Arabidopsis contain a family of PP1 genes and/or pseudogenes. In this study, we report the isolation of five distinct Arabidopsis cDNA clones (TOPP1, TOPP2, TOPP3, TOPP4 and TOPP5) which encode the catalytic subunit (PP1c) of type 1 protein phosphatases. Genomic Southern blot analyses indicate that these clones are the products of five distinct genes and that an additional 2-3 PP1c genes and/or pseudogenes may be present in the Arabidopsis genome. The derived amino acid sequences of the TOPP clones are very similar to published sequences of PP1c from animals, fungi and plants. Four of the TOPP amino acid sequences show unique structural features not observed in other PP1c sequences from fungi or animals. All of the TOPP genes are expressed in Arabidopsis roots, rosettes and flowers, although TOPP1, TOPP2 and TOPP3 appear to be expressed at higher levels in these tissues than TOPP4 and TOPP5.

Amino Acid Sequence↗
PubMed1993

Developing a stable bilateral model of parkinsonism in rhesus monkeys.

The non-human primate models of Parkinson's disease which have been developed using the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine) have proven to be either unstable or variable, or to display only a limited subset of parkinsonian features. The present study examined a new two-stage lesion approach in which MPTP was administered via the carotid arteries. The first infusion through one artery produced a hemiparkinsonian state and was followed several months later by a second MPTP infusion into the contralateral carotid artery to induce bilateral parkinsonism. Animals receiving lesions were evaluated using a battery of tests which included a monkey parkinsonism rating scale, a movement time-task and continuous monitoring of home cage activity. All animals monitored showed significant decreases in activity levels of up to 95% following the second lesion. These decreased activity levels remained stable throughout the observation period of up to 12 months postlesion. In addition to the decreased home cage activity, bilaterally lesioned animals displayed bilateral parkinsonian features including akinesia, bradykinesia, rigidity, tremor and balance and gait disturbances which were stable, following an acute period of up to 45 days, for the remainder of the study. Administration of levodopa increased activity levels and reduced motor dysfunctions. Thus, a two-stage bilateral lesion approach, utilizing the neurotoxin MPTP, appears to provide a less variable and relatively stable model of bilateral Parkinson's disease in nonhuman primates. Treated animals display the cardinal features of parkinsonism and respond appropriately to the standard antiparkinsonian drug, levodopa.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

A tentative cost-utility analysis of road safety education.

This paper sets road safety education in a health promotion context and describes the application of cost-utility analysis to the economic evaluation of road safety education in New South Wales. The application is tentative and designed to illustrate the advantages of the approach rather than to demonstrate the cost-effectiveness of road safety education.

Accidents, Traffic↗
PubMed1993

Predicting response to amitriptyline in posttraumatic stress disorder.

OBJECTIVE: This study evaluated the relation between baseline clinical phenomena and response to amitriptyline in patients with posttraumatic stress disorder (PTSD). METHOD: Data were obtained from an 8-week placebo-controlled, double-blind study of combat veterans. Bivariate and multivariate statistics were used to evaluate the relations between the following variables and outcome: age, depression, anxiety, severity of PTSD symptoms, personality, psychiatric comorbidity, level of exposure to trauma, and individual symptoms of depression, anxiety, and traumatic stress. Outcome measures were scores on the Clinical Global Impression scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Impact of Event Scale. RESULTS: Drug response was related to lower baseline levels of depression, neuroticism, combat intensity, anxious mood, impaired concentration, somatic symptoms, feelings of guilt, and one intrusion and four avoidance symptoms of PTSD. CONCLUSIONS: The results demonstrate that response to amitriptyline is related to measures of depression, anxiety, PTSD, personality, and intensity of combat trauma. Similar relationships were not observed in the placebo group, suggesting a specific relationship to the drug.

Amitriptyline↗
PubMed1993

Survey report on forensic nursing.

1. There are at least 1,200 registered nurses working in psychiatric forensic facilities, 5% of whom are master's prepared. In 1991, approximately 1,900 student nurses were affiliated with an institution providing evaluation and treatment for mentally ill offenders. 2. Based on the response to this survey, there is an eagerness to develop a professional network of forensic psychiatric nurses. The nature of this practice tends to be isolating, with heretofore infrequent opportunities to share common concerns and challenges. 3. Forensic psychiatric nurses represent a stable work force of substantial tenure. The most rewarding aspects of forensic nursing identified by the survey were the potential for autonomous professional practice and the unique challenges of providing care in a security environment.

Curriculum↗
PubMed1993

Pharmacology of 2-amino-1,4-dihydro-4-(2-[4-[4-(2-methoxyphenyl)-1- piperazinyl]butylsulfinyl]phenyl)-6-methyl-5-nitro-3-pyridine carboxylic acid methyl ester (XB513), a novel calcium agonist with alpha-1 adrenergic receptor antagonistic.

2-Amino-1,4-dihydro-4-(2-[-4[4-(2-methoxyphenyl)-1-piperazinyl]- butylsulfinyl]phenyl)-6-methyl-5-nitro-3-pyridine carboxylic acid methyl ester (XB513) was designed to combine the calcium agonistic and alpha-1 adrenergic receptor antagonistic properties in the same molecule. It inhibited the specific binding of [3H] nitrendipine in rat cardiac ventricular membranes with an IC50 of 1.2 microM, which is 20-fold greater than the standard calcium agonist Bay K 8644. It displaced [3H]prazosin in rat brain membranes with an IC50 of 29 nM. XB513 caused concentration-dependent positive inotropic responses in isolated electrically paced guinea pig left atria with an EC50 of 1.2 microM and was 10 times less potent than Bay K 8644. In rabbit aorta, XB513 inhibited the contractile effect of 16 nM norepinephrine with an IC50 of 89 nM. In an acute heart failure dog model produced by an overdose of propranolol, XB513 at 0.3 to 3 mg/kg i.v. dose-dependently reversed the decreased mean arterial pressure, cardiac output and dP/dt as well as the increased left ventricular end diastolic pressure induced by propranolol. In conscious instrumented dogs, XB513 at 0.1 and 0.3 mg/kg i.v. increased dP/dt and heart rate significantly, with a minor effect on mean arterial pressure. In summary, this study demonstrates that XB513 is a novel chemical entity possessing both calcium agonistic and alpha-1 adrenergic receptor blocking properties and thus may represent a new class of agents for the treatment of congestive heart failure.

Adrenergic alpha-Antagonists↗
PubMed1993

Identification of AT2 angiotensin receptors on Swiss 3T3 cells.

Swiss 3T3 cells express high-affinity receptors for angiotensin II (KD = 0.8 nM, 110,000 receptors/cell). Binding of the peptide to these receptors did not activate phosphatidylinositol 4,5 bisphosphate hydrolysis, and did not increase intracellular [Ca2+] or activate protein kinase C. The relative binding affinities of highly-selective antagonists characterised these receptors as the AT2 subtype. However, in contrast to the signalling events reported in some other cells that express AT2 receptors, AII had no apparent effect on either cyclic GMP levels or phosphotyrosine phosphatase activity in Swiss 3T3 cells. Furthermore, angiotensin II (either alone or in combination with growth factors) was not mitogenic to Swiss 3T3 cells.

3T3 Cells↗
PubMed1993

New perspectives in angiotensin system control.

The 'angiotensin system' is expressed at the whole body, organ/tissue and cellular levels through the action of angiotensin II at specific receptors. An appreciation of the full scope of the actions of angiotensin II (endocrine, paracrine and autocrine) has been made possible by the discovery of the non-peptide angiotensin II receptor antagonists, losartan (DuP 753/MK954)(AT1-selective) and PD123177 (AT2-selective). Virtually all of the known effects of angiotensin II are blocked by losartan and designated AT1. Selective AT1 receptor blockade with losartan lowers BP in angiotensin II-dependent models of hypertension, reduces cardiac hypertrophy, improves haemodynamics in models of cardiac failure and reduces the intimal response to vascular injury. AT2 sites have been localised in distinct parts of the brain and in foetal tissue. The functional role of the AT2 sites remains controversial, but possible roles in neuronal ion channel function and collagen metabolism in fibroblasts have been reported. AT1 (losartan-sensitive) receptor subtypes have now been cloned from several rat tissues, suggesting that selective agents of the future may be even more specifically targeted. New perspectives in the control of the angiotensin system continue to evolve rapidly as the new receptor antagonists and molecular biology techniques expand our understanding of angiotensin II.

Amino Acid Sequence↗
PubMed1993

National pathology manpower survey of 1991. Projected needs in community hospitals and private laboratory practice.

The third survey of a representative group of pathologists in community practice confirms the prediction based on the 1987 and 1988 surveys that there would be a growing deficit in the number of pathologists in this practice setting. There is an increasing number of reported vacancies in pathology groups and a significant increment in the percentage of older pathologists, with 32% being older than 54 years of age in 1991, compared with 25% in 1987. Projections based on the plan of individual respondents to retire and the anticipated changes in practice groups suggest that there will continue to be more pathologists leaving practice than new pathologists entering the specialty.

Adult↗