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Biomedical subjects

M Denison

Publications and source records attributed to M Denison.

15 recordsLinked to original sources

Australian experience with the Freehand System for restoring grasp in quadriplegia.

BACKGROUND: The purpose of the present study was to document the value of an implanted multichannel neuroprosthesis (Freehand System) for restoring hand grasp in the first Australians to receive this device. METHODS: Hand function in C5 quadriplegic patients was assessed via measurement of pinch forces, a grasp release test and tests of activities of daily living (ADL). Comparisons were made between presurgery scores and scores recorded after rehabilitation when the neuroprosthesis was and was not in use. RESULTS: A significant difference for both lateral pinch (P = 0.003) and palmar grasp (P = 0.003) was found between forces recorded with and without the use of the neuroprosthesis after rehabilitation, but not between forces recorded presurgery and during rehabilitation without the neuroprosthesis. All subjects were able to grasp, move and release more objects within the 30-s test period with the neuroprosthesis than without it. Collective results for the eight ADL tests for all six subjects show that, in 35 of the 48 (73%) occasions, less physical assistance and/or adaptive equipment was required when the Freehand system was employed compared to when it was not used. In 41 of the 48 (85%) occasions, the six subjects expressed a preference for using the neuroprosthesis to perform these activities of daily living. Twelve months after rehabilitation, five of the six subjects still used the neuroprosthesis daily or every second day. CONCLUSION: The Freehand neuroprosthesis has provided useful hand function with few surgical and technical difficulties in these patients. Regular ongoing use of the device indicates user satisfaction.

Activities of Daily Living↗

Regulation of CYP1A1 by indolo[3,2-b]carbazole in murine hepatoma cells.

To determine the basis for unexpected differences in CYP1A1 inducing potencies and efficacies for the diet-derived indole derivative, indolo[3,2-b]carbazole (ICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we conducted a systematic analysis of events involved in the induced expression of CYP1A1 in murine hepatoma-derived cell lines (Hepa-1). In contrast to the effects of TCDD, induction kinetics and CYP1A1 mRNA half-life were dependent on ICZ concentration, and the response from low doses of inducer was transient due to rapid clearance of ICZ. TCDD and ICZ produced the same maximum response (i.e. equal efficacies) from a TCDD-responsive CAT reporter construct in Hepa-1 cells. When measured by the immediate responses associated with CYP1A1 expression, including cellular uptake of inducer, receptor transformation and binding to DRE (gel mobility shift assay), initiation of transcription (nuclear run-on assay), and short-term accumulation of mRNA (Northern blot assay), ICZ also exhibited an efficacy equal to that of TCDD and a potency that corresponds to its receptor affinity. ICZ is a potent and selective noncompetitive inhibitor of ethoxyresorufin O-deethylase activity (Ki = 1.5 nM). Taken together these results indicate that ICZ is a bifunctional modulator of CYP1A1 expression with intrinsic efficacy equal to that of TCDD.

Animals↗

Survival experience of 789 children with the acquired immunodeficiency syndrome.

To define predictors of survival we studied longitudinal histories of 789 New York State Medicaid-enrolled children diagnosed with acquired immunodeficiency syndrome (AIDS) from 1983 to 1989 and followed through 1990. Median survival times for 3 severity groups of AIDS-defining conditions were 66, 48 and 9 months. In a proportional hazards model, the relative risk of death for the most vs. least severe group was 3.33 (95% confidence interval, 2.53, 4.37) and the relative risk for children < 6 months old at diagnosis vs. older children was 1.81 (95% confidence interval, 1.41, 2.34). We increased our ability to predict death by using a 4-category severity index that assesses both the AIDS-defining diagnosis and clinical complications within 3 months of diagnosis (relative risk, 5.27; 95% confidence interval, 3.16, 8.78 for most vs. least severe). These analyses offer new clinical severity measures and reveal that, regardless of the AIDS-defining diagnosis, children with AIDS who are < 6 months old have a poor prognosis.

Acquired Immunodeficiency Syndrome↗

Neutrophil function after exposure to polychlorinated biphenyls in vitro.

Polychlorinated biphenyls (PCBs) are known to be immunotoxic, yet the effects on neutrophil (PMN) function are not well characterized. We incubated PMNs isolated from rat peritoneum with a mixture of PCB congeners, Aroclor 1242, in the absence or presence of either phorbol myristate acetate (PMA) to stimulate generation of superoxide anion (O2-) or N-formyl-methionyl-leucyl-phenylalanine (fMLP) to induce degranulation (measured as release of beta-glucuronidase). Aroclor 1242 alone stimulated O2- production at a concentration of 10 micrograms/ml. Significant cytotoxicity was not observed under these conditions. This concentration of Aroclor 1242 also increased O2- generation in PMNs activated with 20 ng PMA/ml. In the presence of a concentration of PMA (2 ng/ml) that by itself did not stimulate production of O2-, 1 microgram Aroclor 1242/ml caused significant generation of O2-, indicating synergy between Aroclor 1242 and PMA. Aroclor 1242 caused release of beta-glucuronidase from quiescent PMNs; however, in PMNs stimulated with fMLP to undergo degranulation, Aroclor 1242 inhibited release of beta-glucuronidase. The effects of two PCB congeners, one that binds to the Ah receptor (3,3', 4,4'-tetrachlorobiphenyl) and one that has little affinity for this receptor (2,2', 4,4'-tetrachlorobiphenyl) were examined. 3,3', 4,4'-Tetrachlorobiphenyl had no effect on PMN function in vitro, whereas 2,2', 4,4'-tetrachlorobiphenyl had effects similar to those observed with Aroclor 1242. These results indicate that PCBs affect PMN function in vitro in a complex manner, stimulating or inhibiting function under different conditions. These effects are apparently not mediated through the Ah receptor.

Animals↗

Ventilators: in-service performance with Biotek ventilator testers.

The assessment of mechanical ventilator performance is a complex task requiring measurement of a number of different transducers under a variety of conditions. The use of dedicated testing equipment can alleviate the complexity of the experimental apparatus. This paper assesses the accuracy and versatility of the Biotek VT-1 and VT-2 dedicated ventilator testers. Results show that the testers perform within the manufacturer's specifications and have the required flexibility to be used in investigating faults reported with ventilators.

Equipment Failure↗

Effect of different pump mechanisms on transfusion of blood.

Sometimes infusion pumps are used to deliver whole blood to patients. However, in doing so there is a potential for damage to red cells from mechanical stresses in the pump, resulting in haemolysis. In order to investigate the degree of haemolysis caused by different pumps and therefore their suitability for whole blood infusion, we compared the performances of commonly used volumetric pumps (AVI 400; IVAC 560; IVAC 631 and IMED 927) with different pumping mechanisms. Our results show that the maximum haemolysis (3.9 mg/100g) was caused by the IVAC 560 and the least (1.08 mg/100g) by the AVI 400.

Blood Transfusion↗

Identification of putative polymerase gene product in cells infected with murine coronavirus A59.

The virion RNA of mouse hepatitis virus, strain A59 (MHV-A59) is believed to be the mRNA for the viral RNA-dependent RNA polymerase. The cell-free translation of virion RNA results in the synthesis of two predominant products p220 and p28 (M. R. Denison and S. Perlman, 1986, J. Virol. 60, 12-18). p28 is a basic protein and is readily detected by two-dimensional gel electrophoresis. When infected cells and isolated virions were assayed for this protein by two-dimensional gel electrophoresis, p28 could be detected in infected cells labeled at late times after infection, but not at early times or in purified virions. p28 represents the first protein product of the putative coronavirus polymerase gene to be identified in infected cells.

Animals↗

Anaphylactoid reactions to Escherichia coli and Erwinia asparaginase in children with leukemia and lymphoma.

The incidence and clinical characteristics of anaphylactoid reactions to intravenous asparaginase were assessed in 196 patients given E. coli asparaginase and 49 patients given Erwinia asparaginase. All patients were given a 50 IU intravenous test dose followed in 30 min by the full dosage (10,000 IU/m2), if no reaction occurred to the test dose. Twenty-nine of 196 patients (14.8%) given E. coli asparaginase had an anaphylactoid reaction, occurring after their first through 12th doses. The probability of an anaphylactoid reaction was significantly greater in those patients not receiving concomitant prednisone-vincristine and patients with a hiatus between courses of asparaginase therapy. By logistic regression analysis, other variables such as age, sex, race, diagnosis, total number of doses and concurrent methotrexate or arabinosylcytosine did not contribute significantly to the probability of a reaction. Twenty-three of the patients who had reacted to E. coli asparaginase and 26 patients who had not reacted to E. coli asparaginase were subsequently given Erwinia asparaginase. Seven of these 49 patients (14%) had an anaphylactoid reaction. The probability of a reaction to Erwinia asparaginase was significantly related to a prior reaction to E. coli asparaginase, concomitant prednisone-vincristine therapy, total number of asparaginase doses, number of prior E. coli asparaginase doses, and diagnosis, when assessed by a logistic regression model. However, after adjusting for prior reaction to E. coli asparaginase and the total number of asparaginase doses given, the other variables did not contribute significantly to the probability of a reaction. Only 5/29 patients reacting to E. coli asparaginase and 1/7 reacting to Erwinia asparaginase had a reaction to the test dose. None of the reactions were fatal.

Adolescent↗

Cisplatin disposition in children and adolescents with cancer.

The disposition of cisplatin was evaluated in 28 children and adolescents with cancer, as part of a phase II clinical trial. Patients received either 30 mg/m2 (11) or 90 mg/m2 (17) of cisplatin as a 6-h IV infusion. Serum samples and divided urine collections were obtained over 48 h following completion of the cisplatin infusion, and were assayed in duplicate for total platinum by atomic absorption spectrophotometry. Serum samples obtained up to 4 h after three cisplatin infusions were assayed for parent (free) cisplatin following ultrafiltration. The mean (+/- SE) elimination half-life of free cisplatin in serum was 1.3 (+/- 0.4) h. Serial serum concentrations of total platinum following 90 mg/m2 dosages were adequately described by a biexponential equation. The mean (+/- SE) serum T 1/2 alpha of total platinum was 0.42 (+/- 0.10) h and the mean (+/- SE) T 1/2 beta was 44.43 (+/- 8.24) h. The intercompartment distribution rate constants of a two-compartment kinetic model indicate extensive tissue accumulation of total platinum, with a rate of transport into tissue compartments (K12) that is about six times the rate of transport out of tissues (K21). The mean (+/- SE) renal clearance of total platinum from 0-3 h was 37.36 (+/- 11.96) ml/min/m2 and 35.8 (+/- 13.6) ml/min/m2 for the 30 mg/m2 and 90 mg/m2 groups, respectively. This value decreased to 3.25 (+/- 0.94) and 2.16 (+/- 0.4) ml/min/m2 for the two groups by the 6-12 h interval, and remained between 1 and 3 ml/min/m2 for the duration of the observation period. The ratio of total platinum clearance to creatinine clearance decreased significantly (P less than 0.05) beginning 3 h post-infusion. The change in renal clearance of total platinum is apparently a function of two independent first-order processes for renal clearance of parent drug and cisplatin metabolites.

Adolescent↗