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Biomedical subjects

T Dunn

Publications and source records attributed to T Dunn.

At least 55 records · Page 3Linked to original sources

The anti-tumour activity of ifosfamide on heterotransplanted testicular cancer cell lines remains unaltered by the uroprotector mesna.

Ifosfamide is clinically used in combination chemotherapy regimens for the treatment of patients with high-grade lymphomas, sarcomas and metastatic germ cell tumours. In order to reduce the oxazophosphorine-related urothelial toxicity, sodium mercaptoethane sulphonate (mesna) is used in different schedules following the administration of ifosfamide. The proposed mechanism of mesna activity is the binding of toxic oxazaphosphorine metabolites such as acrolein in the urine of the patients. Since an influence of mesna on ifosfamide anti-tumour activity is controversial, the current study has used xenografts from two human testicular cancer cell lines heterotransplanted into nude mice to study the anti-tumour activity of ifosfamide in combination with different dosages and schedules of mesna. In both human testicular cancer cell lines, H 12.1 and 2102 EP, ifosfamide demonstrated anti-tumour activity as a single agent. No reduction in ifosfamide activity was observed with the application of mesna at a dose range from 50% to 200% of the ifosfamide dose. Furthermore, the application of mesna before and 3 h after ifosfamide, a schedule used in many clinical protocols because of the short half life of mesna, not only maintained high ifosfamide anti-tumour activity but also seemed to be associated with the lower systemic and urothelial toxicity of ifosfamide therapy compared with ifosfamide given alone. In conclusion, the experimental in vivo system using human heterotransplanted testicular cancer cell lines confirms the significant anti-tumour activity of ifosfamide in malignant germ cell tumours and demonstrates that mesna does not impair ifosfamide anti-tumour activity in this model. These results are most likely transferable to the use of mesna in patients with metastatic testicular cancer.

Animals↗

Evaluation of topical ibuprofen cream in the treatment of acute ankle sprains.

One hundred patients who presented to the accident and emergency (A&E) department with an acute ankle sprain were entered into a study to determine the efficacy of topical ibuprofen cream by using a double-blind placebo controlled design in a single type of soft-tissue injury. The subjects were given either topical ibuprofen cream or a placebo cream in addition to the standard management of the department. Patients kept diaries recording walking ability and pain visual analogue scales for resting, standing and walking. A total of 51 patients returned diaries that were suitable for analysis. Patients using the topical ibuprofen cream had significant reduction in pain scores over the first 48 h of treatment.

Administration, Topical↗

Managing asthma in accident and emergency departments: an assessment in non teaching hospitals.

BACKGROUND: The management and follow-up of asthma patients presenting at Accident and Emergency (A&E) departments have mostly been studied in children's hospitals or specialised teaching hospitals. AIMS: To study the adequacy of assessment, treatment and follow-up of patients presenting at A&E departments in non-teaching hospitals. To compare the assessment and management of asthma in A&E departments among hospitals in a health region. METHODS: A twenty-five per cent sample of presentations to A&E departments in all public hospitals in the Illawarra for one year was selected for a case note audit. Information on demographics, assessment, management and referral was extracted from the A&E case notes and medical records of cases with documentation of a final diagnosis of asthma. Chi square and Fischer's Exact tests were used for comparisons among hospitals. RESULTS: Of 359 presentations with a final diagnosis of asthma, 88% were self referred and only 5% were first presentations. Objective measures of airways obstruction was not documented in 34% of admissions and 48% of nonadmissions. There was no documented follow-up in 28% of cases. The assessment and management of asthma in A&E was significantly poorer in smaller hospitals. CONCLUSION: Evidence of high use of A&E as a primary care facility by asthma patients was found in the study. There is a need to implement protocols to optimise assessment and treatment of asthma in smaller hospitals.

Adolescent↗

Community-based cholesterol screening and education to prevent heart disease: five-year results of the North Coast Cholesterol Check Campaign.

A cardiovascular disease screening and education campaign was conducted throughout the North Coast Region of New South Wales from 1987 to 1991. Objectives were: to screen 20 per cent of the adult population for blood cholesterol and other heart disease risk factors; to raise awareness of the risks associated with a high-fat diet; to provide nutrition counselling and referral advice for those with elevated cholesterol; and to monitor these participants' cholesterol levels with a follow-up test at three months. During the five years, 42,869 individuals or 18 per cent of North Coast adults participated, with some overrepresentation of women aged 40 to 60 years. Initially, 65 per cent of participants had elevated cholesterol levels (> or = 5.5 mmol/L) and 46 per cent were overweight (body mass index over 25). A three-month retest was offered to all participants with elevated cholesterol, of whom 53 per cent attended. Participants who received nutrition counselling generally reported dietary changes which were reflected in significant cholesterol and weight reductions. Of participants who attended retest, 63 to 87 per cent had reduced cholesterol levels and 57 to 71 per cent reduced weight. A stratified random sample of participants was retested at one and three years. Reductions in cholesterol were well maintained for one year but showed signs of relapse after three years. There was a tendency for initially lower cholesterol levels to increase over a three-year period. Contributing factors included aging, regression to the mean and complacency. Maintenance may be enhanced by regular reinforcement of nutrition changes and development of more supportive environments.

Adult↗

In vivo evidence of complete circumvention of vincristine resistance by a new triazinoaminopiperidine derivative S 9788 in P388/VCR leukemia model.

S 9788, a new triazinoaminopiperidine derivative, was found to be a potent reversant of vincristine resistance in the in vivo murine leukemic P388/VCR model. In two treatment regimens (Q4D days 1, 5 and 9 and QD days 1-9), S 9788 enhanced the antitumor activity of vincristine in a dose-dependent manner, resulting in a complete circumvention of drug resistance for well-tolerated doses of S 9788. S 9788 was also effective in enhancing therapeutic effects of vincristine in the treatment of sensitive P388-bearing mice. These results strongly suggest that S 9788 may be a potential candidate for circumvention of multidrug resistance (MDR) in clinical practice.

Animals↗

Regulation of the expression of some genes for enzymes of glutathione metabolism in hepatotoxicity and hepatocarcinogenesis.

The reversible stage of tumor promotion, which follows the stage of initiation and precedes that of progression in multistage carcinogenesis, is a unique example of reversible toxicity in biological systems. In order to study the molecular mechanisms involved in the action of promoting agents during this stage, the regulation of the expression of genes for two enzymes of glutathione metabolism, gamma-glutamyl transpeptidase (GGT) and the placental isozyme of glutathione S-transferase (GST-P), was studied under several different conditions of promotion during multistage hepatocarcinogenesis in the rat. Promotion by phenobarbital caused an increased expression of both of these genes in altered hepatic focal lesions, although this was somewhat more variable in the case of the GGT gene. C.I. Solvent Yellow 14, an industrial dye, served as an effective promoting agent. Feeding this dye resulted in a dramatic increase in the expression of GST-P, but not that of GGT in altered hepatic foci. Factors in crude, cereal-based diets inhibited the stage of promotion by diethylnitrosamine, but enhanced promotion by phenobarbital in a synergistic manner. In contrast, at least one purified diet had the converse effect during this stage. The mRNA levels of GST-P were uniformly elevated dramatically in reversible nodules and neoplasms of rat liver that had been induced by diethylnitrosamine and phenobarbital promotion. In contrast, the level of GGT mRNA was somewhat variable, with an occasional neoplasm exhibiting almost a background level of expression of this gene. Therefore, the altered regulation of multiple genes in hepatocytes during the stage of promotion can vary with the promoting agent itself; this process may be related to the heterogeneous gene expression seen in hepatic neoplasms. A possible role for specific DNA sequences in the 5' flanking regions of such genes is considered. In addition, a cDNA clone to the mRNA of human liver GGT was isolated and sequenced. The homology of the coding sequence of the human liver GGT mRNA to that of rat kidney GGT mRNA was striking.

Animals↗

A disinfectant delivery system for control of micro-organisms in urine collection bags.

We developed a formaldehyde delivery system for urine collection bags and evaluated its effectiveness in suppressing the growth of bacteria in simulated human urine. The system was composed of paraformaldehyde in a polymeric carrier. We determined that inoculation of small numbers of Escherichia coli and Pseudomonas aeruginosa in urinary bags with a continuous flow of synthetic urine (40-80 ml h-1) quickly gives rise to high levels of contamination. This single tablet delivery system, however, proved bacteriostatic or bactericidal for both organisms over the 10-day lifespan. The formaldehyde concentration in the synthetic urine was c. 90 micrograms ml-1 or more during tests.

Disinfection↗

Isolation and nucleotide sequence of the cDNA for rat liver serine dehydratase mRNA and structures of the 5' and 3' flanking regions of the serine dehydratase gene.

Rat serine dehydratase cDNA clones were isolated from a lambda gt11 cDNA library on the basis of their reactivity with monospecific immunoglobulin to the purified enzyme. Using the cDNA insert from a clone that encoded the serine dehydratase subunit as a probe, additional clones were isolated from the same library by plaque hybridization. Nucleotide sequence analysis of the largest clone obtained showed that it has 1444 base pairs with an open reading frame consisting of 1089 base pairs. The deduced amino acid sequence contained sequences of several portions of the serine dehydratase protein, as determined by Edman degradation. Rat liver serine dehydratase mRNA virtually disappeared from livers of rats fed a protein-free diet for 5 days. Several genomic clones were isolated from two libraries. Determinations of the transcription start site and the structure of the 3' flanking region of the gene indicated that the coded mRNA is 1504 nucleotides long. The 5' promoter region contained a variety of sequences similar to several consensus sequences believed to be important for the regulation of specific gene expression.

Amino Acid Sequence↗

Group benefit financing and managed care: linking the rewards of risk taking to funding methods.

The marriage of the delivery and insurance mechanisms is key to the managed care, preferred provider concept, for it holds potential for cost-effective optimization of delivery and marketing efforts. It is, however, necessary to understand each component of the marriage, if the benefits are to be enjoyed. This article explores the five major benefit plan financing arrangements in use today and examines their implications for risk-reward sharing arrangements in a managed care environment.

Financial Management↗

LH response to GnRH infusion in postpartum, fall-lambing ewes subjected to prepartum energy restrictions.

Fall-lambing western range ewes were fed either a high-or low-energy ration the last two months of gestation and were fed protein and energy in excess postpartum. GnRH was infused for 10 hours on day 5 or 26 postpartum. Blood samples were collected at 20-minute intervals during infusion and radioimmunoassayed for LH. Net weight change from day 60 prepartum to day 1 postpartum was 0.67 +/- 1 kg vs. -6.9 +/- 1.5 kg (mean +/- SE) for the high-and low-energy groups, respectively (P < 0.05). Nutritional treatment had no effect on LH response at either day 5 or day 26 postpartum, althoughthe day 26 LH response to GnRH was greater (P < 0.05) than the day 5 LH response. LH response was greater (P < 0.05) in ewes that gained weight prepartum vs. ewes that lost weight prepartum, but only in ewes infused on day 5 postpartum.

Journal Article↗

Determining actual costs in central processing: a case study.

Access to accurate cost information is integral to product line development and management. It is also necessary under the PPS system which reimburses hospitals at a fixed rate for the provision of health care and puts hospitals at risk for their costs. The following case study presents a methodology for identifying and analyzing the costs of providing central processing services.

Accounting↗

Upstream repression and CRP stimulation of the Escherichia coli L-arabinose operon.

Repression of the Escherichia coli araBAD promoter, PBAD, was studied using a mutant PBAD promoter (cip-5) that is expressed in the absence of the two proteins required for PBAD induction, AraC protein and the cyclic AMP receptor protein (CRP-cAMP). Like the wild type promoter, cip-5 was repressed by AraC protein, and this repression required a site well upstream of the transcriptional start site. cip-5 was used to determine whether repression results from interference with the functioning of either AraC protein at araI and/or CRP-cAMP. Repression of cip-5 was eliminated by a point mutation within the AraC protein binding site araI but was not affected in the absence of CRP-cAMP. These results suggest that repression involves an interaction between two AraC protein binding sites located over 200 nucleotides apart. Our results also suggest that the majority of the CRP requirement for PBAD is a result of PBAD repression. When repression was abolished by deletion of the araO2 site, the requirement for CRP-cAMP in PBAD induction was greatly reduced.

AraC Transcription Factor↗