Nursing education: the diploma programs.
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Education, Nursing, Diploma Programs↗
Biomedical subjects
M Courtney
Publications and source records attributed to M Courtney.
Use of synthetic oligonucleotides in gene isolation and manipulation.
Great progress has occurred in the techniques of synthesis of DNA molecules of defined sequences in terms of speed, length of the obtained oligonucleotides, and automation of the processes. Corresponding progress also occurred in the ways of using synthetic DNA in molecular biology and recombinant DNA research. Screening of cloned DNA sequence banks with long, unique oligonucleotides, provided a new approach to isolate the genes for proteins which are present in very small quantity. This technique can present considerable advantages over the more classical use of mixtures of oligonucleotides, in reducing the number of potentially positive clones on a primary screen, and enabling cloning with a minimum of amino acid sequence data. Synthetic oligonucleotides also provide the basis of a set of techniques for site-directed mutagenesis of DNA sequences. This allows the possibility of engineering the structure of particular proteins, and the properties of new variants can be tested by expressing the protein in a heterologous host. An example of this approach is the production of variants of human alpha 1-antitrypsin. A variant where valine replaces the methionine at the active site is equally active as an antielastase, but no longer susceptible to oxidative inactivation. A second variant, where arginine replaces the methionine, now functions as an antithrombin, but no longer inhibits elastase. Total gene synthesis is now feasible for larger and larger genes, and some of the recent strategies of whole gene synthesis are presented.
Amino Acid Sequence↗
Synthesis in E. coli of alpha 1-antitrypsin variants of therapeutic potential for emphysema and thrombosis.
The primary function of alpha 1-antitrypsin (alpha 1-AT), an antiprotease produced by the liver, is the inhibition of neutrophil elastase, a protease capable of hydrolysing most connective tissue components. The importance of alpha 1-AT is demonstrated by the high incidence of early-onset emphysema in individuals with hereditary alpha 1-AT deficiency (Type PiZZ), in whom serum levels of alpha 1-AT are 10-20% of normal. Oxidants in tobacco smoke can inactivate alpha 1-AT in vitro, and studies have shown that alpha 1-AT from the lungs of individuals who smoke cigarettes may also be partially inactivated, perhaps explaining the high incidence of emphysema associated with cigarette smoking. Oxidative inactivation is probably due to modification of the Met residue (Met358) at the P1 subsite position of the elastase binding site of the protein. To study the possibility of modulating the biological properties of alpha 1-AT, we have introduced selected sequence modifications at the reactive site by in vitro mutation of a cloned alpha 1-AT complementary DNA. We describe here the characterization of two alpha 1-AT analogues produced in Escherichia coli. The first, alpha 1-AT(Met385----Val), is not only fully active as an elastase inhibitor but is also resistant to oxidative inactivation. The other, alpha 1-AT(Met358----Arg), no longer inhibits elastase but is an efficient thrombin inhibitor. The active site of the latter is identical to that of the alpha 1-AT (Pittsburgh) variant, which was associated with a fatal bleeding disorder.
Amino Acid Sequence↗
Gene therapy study of cytokine-transfected xenogeneic cells (Vero-interleukin-2) in patients with metastatic solid tumors.
On the basis of compelling preclinical data in cats and dogs, we initiated a clinical gene therapy study in nine patients with advanced solid tumors using xenogeneic fibroblasts secreting human interleukin (IL)-2 (Vero-IL-2 cells). Cohorts of three successive patients with tumors accessible to computed tomography- or ultrasound-guided injection were treated repeatedly with 5 x 10(5), 5 x 10(6), or 5 x 10(7) Vero-IL-2 cells. The endpoints of the study were feasibility, toxicity, and the clinical and biological effects of this novel approach to immunotherapy of cancer. Histopathological, immunological, and molecular analyses were performed on biopsy specimens of tumors and blood samples before, during, and after treatment. Treatment was well tolerated, and toxicity consisted of transient fever in one patient and short-lived, mild itching and erythema in two others. One patient with soft-tissue sarcoma showed a reduction of >90% and >50% of the volume of two distant, noninjected metastases, lasting for 29+ and 26 months, respectively. Four other patients showed stabilization of their disease for 3-9 months; of these patients, one with melanoma developed marked vitiligo. We conclude that repeated injections of < or =5 x 10(7) Vero-IL-2 cells are feasible and safe in heavily pretreated patients with advanced solid tumors. An additional evaluation of an intratumoral application of Vero-IL-2 seems warranted.
Adult↗
Altered specificities of genetically engineered alpha 1 antitrypsin variants.
Seven active site variants of human alpha 1-antitrypsin (alpha 1AT) were produced in Escherichia coli following site-specific mutagenesis of the alpha 1AT complementary DNA. alpha 1AT (Ala358), alpha 1AT (Ile358) and alpha 1AT (Val358) were efficient inhibitors of both neutrophil and pancreatic elastases, but not of cathepsin G. alpha 1AT (Ala356, Val358) and alpha 1AT (Phe358) specifically inhibited pancreatic elastase and cathepsin G respectively. The most potent inhibitor of neutrophil elastase was alpha 1AT (Leu358), which also proved to be effective against cathepsin G. The alpha 1AT (Arg358) variant inactivated thrombin with kinetics similar to antithrombin III in the presence of heparin. Electrophoretic analysis showed that SDS-stable high mol. wt complexes were formed between the mutant inhibitors and the cognate proteases in each case. These data indicate that effective inhibition occurs when the alpha 1AT P1 residue (position 358) corresponds to the primary specificity of the target protease. Moreover, alteration of the P3 residue (position 356) can further modify the reactivity of the inhibitor. Two of the variants have therapeutic potential: alpha 1AT (Leu358) may be more useful than plasma alpha 1AT in the treatment of destructive lung disorders and alpha 1AT (Arg358) could be effective in the control of thrombosis.
Amino Acid Sequence↗
Models of nursing care: a comparative study of patient satisfaction on two orthopaedic wards in Brisbane.
Patient satisfaction measures assist nurses in the evaluation of effectiveness of nursing practice and assist the process of improvement regarding established practice. A comparative study was carried out on 36 patients from a ward using team nursing (Model 1) and 38 patients from a ward using patient allocation (Model 2) in two orthopaedic wards of a 900 bed teaching hospital in Brisbane, Australia. The purpose of the research was to measure if differences in the levels of patient satisfaction were evident. The Patient Satisfaction Survey (Greenhill and Henderson 1997) used in this study encompassed aspects such as patients' feelings and perceptions; nurses' skills, behaviour and attitudes; nurses' communication and education skills; and continuity of care experienced. The results indicated that there were no differences between models of nursing care and levels of patient satisfaction. However, there were significant relationships between patient satisfaction and patients' characteristics such as age, education and health status.
Female↗
Heart transplantation for end-stage cardiomyopathy caused by an occult pheochromocytoma.
Dilated cardiomyopathy has been found in patients with pheochromocytoma. The cardiomyopathy and resultant congestive heart failure can be progressive and fatal, or reversible, if the source of the excess catecholamines is removed. Histologic and autopsy studies revealed a characteristic focal myocarditis and contraction band necrosis, indicating that the circulating catecholamine excess secreted by the pheochromocytoma is the cause of the cardiomyopathy.
Adrenal Gland Neoplasms↗
Safety and efficacy of beta blockade in patients with chronic congestive heart failure awaiting transplantation.
BACKGROUND: Donor availability remains a limiting factor for heart transplantation while transplant waiting time entails significant morbidity and mortality. This study was designed to assess the efficacy and safety of long-term beta blockade as optimization of therapy in patients with severe congestive heart failure already receiving digoxin, diuretics, and converting enzyme inhibitors awaiting transplantation. METHODS: The beta-1 antagonist metoprolol was given to 19 patients with moderate to severe congestive heart failure. Hemodynamic, clinical, and neurohormonal measurements were obtained before drug therapy and after 3 months of treatment. Patients initially received 6.25 mg of metoprolol orally twice daily which was increased to a target dose of 50 mg twice daily over several weeks. RESULTS: Metoprolol produced significant clinical, exercise, and hemodynamic benefits. Long-term therapy was associated with improvements in New York Heart Association class, ejection fraction, 6-minute walk, and peak maximal oxygen consumption. There were significant decreases in heart rate, pulmonary arterial systolic pressure, and left ventricular filling pressure with significant increases in stroke volume index and stroke work index. Four patients were removed from the transplant list after improving to New York Heart Association I. Only one patient required hospitalization during the first 6 months of therapy. There were no deaths caused by progressive heart failure; however, one patient died suddenly. CONCLUSIONS: Beta blockade with metoprolol can be safely administered to patients awaiting heart transplantation producing clinical, exercise, and hemodynamic improvements. Thus, beta blockade may prove to be a safe and cost-effective bridge to transplantation.
Adrenergic beta-Antagonists↗