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Biomedical subjects

M Duffy

Publications and source records attributed to M Duffy.

At least 37 records · Page 2Linked to original sources

The effect of the overall treatment time of fractionated irradiation on the tumor control probability of a human soft tissue sarcoma xenograft in nude mice.

PURPOSE: To study the impact of the overall treatment time of fractionated irradiation on the tumor control probability (TCP) of a human soft tissue sarcoma xenograft growing in nude mice, as well as to compare the pretreatment potential doubling time (Tpot) of this tumor to the effective doubling time (Teff) derived from three different schedules of irradiation using the same total number of fractions with different overall treatment times. METHODS AND MATERIALS: The TCP was assessed using the TCD50 value (the 50% tumor control dose) as an end point. A total of 240 male nude mice, 7-8 weeks old were used in three experimental groups that received the same total number of fractions (30 fractions) with different overall treatment times. In group 1, the animals received three equal fractions/day for 10 consecutive days, in group 2 they received two equal fractions/day for 15 consecutive days, and in group 3 one fraction/day for 30 consecutive days. All irradiations were given under normal blood flow conditions to air breathing animals. The mean tumor diameter at the start of irradiation was 7-8 mm. The mean interfraction intervals were from 8-24 h. The Tpot was measured using Iododeoxyuridine (IudR) labeling and flow cytometry and was compared to Teff. RESULTS: The TCD50 values of the three different treatment schedules were 58.8 Gy, 63.2 Gy, and 75.6 Gy for groups 1, 2, and 3, respectively. This difference in TCD50 values was significant (p < 0.05) between groups 1 and 2 (30 fractions/10 days and 30 fractions/15 days) vs. group 3 (30 fractions/30 days). The loss in TCP due to the prolongation of the overall treatment time from 10 days to 30 days was found to be 1.35-1.4 Gy/day. The pretreatment Tpot (2.4 days) was longer than the calculated Teff in groups 2 and 3 (1.35 days). CONCLUSION: Our data show a significant loss in TCP with prolongation of the overall treatment time. This is most probably due to an accelerated repopulation of tumor clonogens. The pretreatment Tpot of this tumor model does not reflect the actual doubling of the clonogens in a protracted regimen.

Animals↗

Quantitative comparison of xenotransplantation of a human soft tissue sarcoma into the subcutaneous tissue of normal, postincision, and postincision plus indomethacin-treated nude mice.

The purpose of this study was to test the hypotheses that (1) surgical wounding can enhance the xenotransplantability of a human soft tissue sarcoma (HSTS26T) into subcutaneous (s.c.) tissue of nude mice, and (2) Indomethacin may reduce the xenotransplantability of this human tumor in the surgical wounding animal model by suppressing angiogenesis. The experimental method was to employ the quantitative transplantation assays (TD50, the number of tumor cells that, on average, would be expected to induce a tumor in 50% of the recipients). After an incisional wound (1.0-1.2 cm long) was made on the right leg of each experimental mouse, tumor cells were inoculated into the surgical wound, or into the contralateral leg at 24 and 72 hr postincision, and in another group tumor cells were inoculated into the wound at 72 hr postincision, plus daily s.c. injection of indomethacin, 2 mg/kg body weight for 8 consecutive days in a separate experiment. Nonincisional mice received the same inoculation as the control groups. The TD50s of surgically wounded groups were 3.5-10.7 times lower than that of the control groups. Significantly lower TD50 values were found in groups of cells inoculated into the surgical wound at 72 hr postincision (P < 0.05 or P < 0.01) and into the contralateral leg at 24 hr postincision (P = 0.05). No significant difference was found between the TD50 values in mice that received cells inoculated at 72 hr postincision plus indomethacin treatment, and those with no wound controls. Our conclusion is that the surgical wound can enhance the xenotransplantability of HSTS26T in nude mice. Indomethacin can decrease this enhancing effect level similar to that in no-wound controls and may prevent tumor recurrence in a surgical wound.

Animals↗

Comparison of 10% povidone-iodine and 0.5% chlorhexidine gluconate for the prevention of peripheral intravenous catheter colonization in neonates: a prospective trial.

The purpose of the study was to compare the efficacy of 10% povidone-iodine with that of 0.5% chlorhexidine gluconate in 70% isopropyl alcohol for the prevention of peripheral intravenous catheter colonization in neonates. This was a multicenter, nonrandomized prospective study in a tertiary neonatal intensive care setting in which povidone-iodine and chlorhexidine gluconate were each used as antiseptic skin preparations over sequential 6-month periods. During the first 6 months of the study when povidone-iodine was in use 9.3% (38 of 408) of catheters were colonized. During the second 6 months of the study when chlorhexidine gluconate was in use, catheter colonization occurred in 4.7% (20 of 418, P = 0.01). Catheter-related bacteremia occurred during only 0.2% (2 of 826) of all catheterizations. Heavy skin colonization before catheter insertion (relative risk, 3.6; 95% confidence interval, 1.9, 7.0), catheterization > or = 72 hours (relative risk. 2.0; 95% confidence interval, 1.01, 3.8) and gestational age < or = 32 weeks (relative risk, 1.8; 95% confidence interval, 1.02, 3.3) increased colonization risk. Ampicillin infusion (relative risk, 0.4; 95% confidence interval, 0.2, 0.7) and 0.5% chlorhexidine gluconate cutaneous antisepsis (relative risk, 0.4; 95% confidence interval, 0.2, 0.8) were factors associated with decreased colonization risk. We conclude that 0.5% chlorhexidine gluconate in 70% isopropyl alcohol appears to be more efficacious than 10% povidone-iodine for the prevention of peripheral intravenous catheter colonization in neonates.

Analysis of Variance↗

The eye of the beholder: housing preferences of inpatients and their treatment teams.

The authors surveyed 80 hospitalized patients with serious mental illness and the patients' treatment teams to compare their perspectives about appropriate housing and support services following hospital discharge. The results showed that the opinions of patients and treatment teams differed markedly on housing preferences but converged on many basic service needs. Patients preferred more independent living arrangements, while treatment teams favored more structured environments. The authors believe that these conflicting views must be reconciled if patient preferences are to be reflected in discharge planning.

Adult↗

Growth and metastatic behavior of five human glioblastomas compared with nine other histological types of human tumor xenografts in SCID mice.

The growth and metastatic behavior of five human glioblastoma multiforme xenografts and nine human xenografts of various histological types were compared in severe combined immunodeficient (SCID) mice. The results demonstrate that the metastatic behavior of the human glioblastoma multiforme xenografts did not differ significantly from a variety of other histological xenografts when evaluated at the same transplantation site in the SCID model. These results are consistent with the hypothesis that the site of glioblastoma multiforme growth influences the extraneural metastatic spread of this disease and lead the authors to suggest that the clinical rarity of distant metastasis is not a fundamental property of these cells. A total of 340 male 7- to 8-week-old SCID mice received subcutaneous transplantation of tumor fragments (21-25 mice per tumor type). The tumor-bearing leg was amputated when the tumor reached a volume of 500 mm3; mice were observed for up to 5 months. There was a trend for a lower take rate, longer latent period, longer volume doubling time (VDT) and growth time (GT) in glioblastoma multiforme as opposed to carcinoma and soft tissue sarcoma xenografts. The highest local recurrence rates (78% and 68%) were observed in two glioblastomas multiforme. Both the glioblastoma multiforme and the other histological xenografts exhibited a widely varying metastatic rate: no correlation was demonstrated between VDT, GT, local control/recurrence, and distant metastasis. These findings show SCID mice to be an attractive model for further biological and preclinical studies of human glioblastoma multiforme.

Adenocarcinoma↗

Bending a promise.

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Health Care Reform↗

Picture of health.

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Data Collection↗

Intratumoral heterogeneity of malignant gliomas measured in vitro.

PURPOSE: To evaluate the extent of intratumoral heterogeneity of radiation sensitivity in malignant gliomas, by comparing the intrinsic radiation sensitivity of different glioma sublines derived from the same tumor. METHODS AND MATERIALS: The study was performed on five early established malignant gliomas (passage 3-10). Each specimen was quickly cut into three equal pieces (except for one specimen, where only two pieces were obtained). Each piece was processed independently, disintegrated into single cell suspension using a cocktail of enzymes. Survival curve assays, using colony formation as an end-point, were performed for each subline. Comparison between the intrinsic radiation sensitivity of sublines was calculated using the surviving fraction at 2 Gy and the mean inactivation dose as the measured parameters. The DNA content of the cell lines as well as their cell cycle analysis was determined using flow cytometry. RESULTS: The mean calculated surviving fraction at 2 Gy of all the sublines was 0.37 +/- 0.14, the mean mean inactivation dose was 1.98 +/- 0.63. The intertumoral coefficient of variation for the calculated surviving fraction at 2 Gy of all cell lines was 38%, while that for intratumoral heterogeneity was 25%. Three of the 5 tumors showed a statistically significant difference in the surviving fraction at 2 Gy and mean inactivation dose values of their sublines (p < 0.05). This difference in radiation sensitivity between sublines of the same tumor was not attributed to a difference either in the ploidy status or in the distribution of cells in the cell cycle. CONCLUSION: There is a significant intratumoral heterogeneity of radiation sensitivity in some malignant gliomas. This heterogeneity may limit the predictive power of surviving fraction at 2 Gy or mean inactivation dose, especially when their values are based upon a single measurement/single biopsy. In the meantime, this heterogeneity may be a factor in the discrepancy between unexpectedly sensitive tumor cell lines in vitro and their high clinical radiation resistance.

Brain Neoplasms↗

Behind closed doors.

The inside story of how Bill and Hillary Clinton fashioned the health-care plan. Their own aides often battled over the Clintons' approach.

Focus Groups↗

Operation Hillary.

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Focus Groups↗

Interphotoreceptor retinoid binding protein (IRBP) enhances rhodopsin regeneration in the experimentally detached retina.

Results obtained in a previous study showed that, compared with a normal eyecup preparation, the amount of rhodopsin regenerated and the rate at which it was resynthesized after bleaching were reduced by about 50% when the skate retina was detached from its pigment epithelium (RPE) and replaced immediately on the apical surface of the RPE (Sun and Ripps, 1992). In the present study, these observations have been extended to preparations in which the detachment procedure was performed under fluid in order to dilute the IRBP content of the interphotoreceptor matrix. The goal initially was to determine whether lowering the IRBP concentration of the subretinal space affected the regenerative process. Using fundus reflectometry, it was found that allowing fluid to enter the subretinal space exposed by the detachment procedure caused profound deficits in both the rate and amount of rhodopsin that regenerated after bleaching. Results obtained with SDS-PAGE and immunohistochemistry showed that the molecular weight of the IRBP extracted from the skate retina is similar to that of many other vertebrate species, and that antibodies prepared against mammalian IRBP react with epitopes on skate IRBP within the interphotoreceptor matrix. Accordingly, it was investigated whether it is possible to reverse the detachment-induced anomalies in rhodopsin kinetics by introducing ligand-free IRBP purified from bovine retina to the subretinal space. Again using fundus reflectometry, it was found that instilling 5 microM of a 130 microM IRBP solution between the neural retina and the RPE increased significantly the rate of regeneration, and more than doubled the amount of rhodopsin reformed in darkness.

Adaptation, Ocular↗

Implementing the Manual Handling Regulations.

When last year's consultative document for the Manual Handling Regulations arrived on her desk Maureen Duffy, like many other OHNs, realised that she had her work cut out. She describes how her company set about achieving compliance with the new legislation.

Accidents, Occupational↗

Canadian physiotherapists' professional identity: an exploratory survey.

This survey was funded and conducted by the Ontario and Canadian Physiotherapy Association Task Force on Professional Identity. Professional identity influences the image an occupation projects to its clients, the public, other occupations and governments. As an aid to planning strategy for advancing the professional image of physiotherapy, an open-ended questionnaire explored Canadian physiotherapists' professional identity. Professional identity is promoted by Canadian Physiotherapy Association (CPA) branches and districts. Most therapists identified their skills and potential benefit for patients, but only 15% identified themselves as a member of a health profession involved in a rewarding career. Physiotherapists have achieved many characteristics of an independent profession, but expressed frustration reveals that some members lack power on a personal and professional level.

Attitude of Health Personnel↗