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Biomedical subjects

G Stevens

Publications and source records attributed to G Stevens.

At least 55 records · Page 3Linked to original sources

Thyroid dose in children undergoing prophylactic cranial irradiation.

PURPOSE: To determine the radiation dose received by the thyroid gland as a result of prophylactic cranial irradiation (PCI) in childhood leukemia and the factors influencing that dose. METHODS AND MATERIALS: The dose to the thyroid resulting from simulated cranial irradiation with parallel opposed lateral fields of an adult anthropomorphic (ART) phantom with both 6 MV X-rays and Cobalt-60 gamma-rays was measured using thermoluminescent dosimeters (TLDs). The dependence of thyroid dose on the distance of the field from the thyroid and the proportions of thyroid dose from stray radiation (leakage, scatter from jaws, etc.) and tissue scattered radiation were measured. The effects of a shadow tray and shielding blocks were also determined. Calculation of thyroid dose using the Clarkson scatter integration method was performed for 6 MV X-rays to compare with the measured doses. In vivo thyroid dose estimates were made using TLD measurements for three children receiving PCI with 6 MV X-rays. RESULTS: Using open, unshielded fields, the thyroid region of the phantom received 1.2-1.4% of the prescribed cranial dose for 6 MV X-rays and 1.5-1.7% for Cobalt-60. For both treatment units, stray radiation accounted for approximately two thirds of the thyroid dose and tissue scatter accounted for the remaining one third. The thyroid dose increased as the field moved closer to the thyroid, with an increasing proportion of the dose due to tissue scatter. Placement of a thyroid shielding block on a shadow tray reduced the thyroid dose by only 20% compared with the open, unshielded setup. Thyroid dose from 6 MV using open fields was affected by the orientation of the collimator. When the inferior field edge was defined by the lower jaw, the dose was reduced by 27% compared with the upper jaw. Good correlation of dose to the thyroid region was obtained between phantom measured doses, in vivo measured doses and calculation of dose using the Clarkson method. CONCLUSION: For PCI doses of 1800 or 2400 cGy in the adult phantom, the dose to the thyroid was 20-40 cGy (1-2%). For small children this could rise to approximately 5% of the prescribed dose, of which half was due to stray radiation. As the thyroid in children is very sensitive to radiation and the dose-response curve for thyroid tumor induction is linear, attempts to shield the thyroid during cranial irradiation are mandatory. Cobalt-60 units should not be used, as the thyroid dose was higher than using 6 MV X-rays. Collimator orientation and the use of shadow trays and shielding were important factors in determining thyroid dose.

Adult↗

Effect of radiation and tirapazamine (SR-4233) on three melanoma cell lines.

In this study the response of three melanoma cell lines to single doses of radiation, to the bioreductive drug tirapazamine (SR-4233) and to the combination of radiation and tirapazamine was determined. Tirapazamine is a bioreductive drug with specific cytotoxicity in hypoxic conditions. Three melanoma cell lines (MM576, MM96L and murine B16-F10) were exposed to increasing concentrations of tirapazamine to assess cytotoxicity under aerobic and hypoxic conditions. Also, clonogenic survival after single doses of 4 MV X-rays was determined under aerobic and hypoxic conditions, with and without 20 microM tirapazamine. Tirapazamine was an effective hypoxic cytotoxin in the three cell lines. The concentrations of tirapazamine causing equal cell kill were 1000 mM for aerobic cells and 50 mM for hypoxic cells. The oxygen enhancement ratios for single X-ray doses were between 2 and 3 for all the cell lines. Addition of 20 microM tirapazamine to hypoxic cells 1 h before irradiation produced the same radiosensitivity as aerobic cells. Tirapazamine had a minimal effect on the radiosensitivity of aerobic cells. Since melanomas are known to contain hypoxic cells which may reduce their radiosensitivity, these in vitro results have demonstrated the potential of tirapazamine to overcome the radioresistance of hypoxia and give encouragement for further studies.

Animals↗

Research attitudes of otorhinolaryngology clinicians: results of the 1996/1997 SOHN Delphi Survey. Society of Otorhinolaryngology and Head-Neck Nurses.

This paper reports the research experience and attitudes of respondents in the Society of Otorhinolaryngology and Head-Neck Nurses (SOHN) Delphi Survey of Otorhinolaryngology (ORL) Nursing Research Priorities. Questions on past experience with research and highest academic level achieved were included in the demographic section of the survey. A Research Attitudes Scale (RAS) was developed, validated, and administered. Results indicate that survey respondents were relative novices to the research arena but had positive attitudes about nursing research (group X = 6.2). Research attitudes scores decreased as scale items became more personal. A discussion of the SOHN Research Committee's structure and activities, as well as suggestions for additional study of SOHN members' research attitudes are offered based on the literature review and study findings.

Attitude of Health Personnel↗

Erbium:YAG laser-assisted cataract surgery.

BACKGROUND AND OBJECTIVE: To assess the safety and efficacy of erbium:YAG laser-assisted cataract removal. PATIENTS AND METHODS: A total of 15 patients underwent cataractous lens removal. All the patients had a visual acuity of 20/50 or worse secondary to senile cataract. The endothelial cell count was calculated preoperatively and at 6 weeks postoperatively. A 2.94-micron-wavelength erbium: YAG laser with a zirconium-fluoride fiber optic and silica tip was used to fracture and emulsify the nucleus. The erbium:YAG laser was chosen due to its high absorption in water, a primary component of a cataractous lens. RESULTS: The postoperative visual acuity was 20/30 or better in all the eyes that were treated with surgery. The endothelial cell loss at 3 months was 0% to 10%. No laser-related complications were noted. A conversion to an ultrasound surgical technique was utilized in six cases. Vitreous loss occurred in one case due to the posterior extension of an anterior capsulotomy tear. CONCLUSION: This study demonstrated the ability of an erbium:YAG laser system to safely and effectively emulsify the lens nucleus. Laser-assisted cataract surgery is a promising new clinical procedure.

Aged↗

Otorhinolaryngology nursing research priorities: results of the 1996/1997 SOHN Delphi survey.

This study was initiated by the Society of Otorhinolaryngology and Head-Neck Nurses, Inc. (SOHN) to establish research priorities for the specialty. Otorhinolaryngology (ORL) Nurses were asked to identify, rate, and rank priorities for ORL nursing research. The survey sample was gleaned from attendees at the 20th Annual SOHN Congress and Nursing Symposium plus a follow-up mailing to active SOHN members who did not attend. A decision-making method, the reactive delphi technique, was employed. Four rounds of soliciting opinions by questionnaires were completed. Data from each round were reviewed and analyzed by three ORL nurse investigators. The respondents were largely actively employed, female SOHN members who were seasoned nurses, experienced in ORL nursing. The majority were Registered Nurses (RN) or held Bachelor of Science (BSN) degrees. They were primarily employed as staff nurses in outpatient settings and working with a general otorhinolaryngology patient population of all ages. The fourteen priorities identified fall in the areas of patient outcomes (three), patient education (three), symptom management (two), patient self-care (two), psychosocial issues (two), and nursing care delivery (two), spanning the practice spectra of all ORL nurse generalists and subspecialists. The top five research priorities identified are; care of neck stomas and related equipment, quality of life in head and neck cancer patients, impact of managed care on ORL nursing care delivery, value of ORL specialty nurses/nursing units, and effective techniques to promote cessation of substance abuse in adolescents. This priority identification provides a baseline for the newly forming SOHN Foundation.

Delphi Technique↗

Oculocutaneous albinism (OCA2) in sub-Saharan Africa: distribution of the common 2.7-kb P gene deletion mutation.

Oculocutaneous albinism (OCA2) is the most common autosomal recessive disorder in the South African Negroid population, occurring with a prevalence of 1/3900 individuals. The OCA2 locus, P, has been mapped to chromosome 15q11-q13 and a 2.7-kb interstitial deletion has been found to be the common mutation in Africa. This study reports the detection of the deletion allele in OCA2-affected individuals from the southern African, Zambian and Central African Republic (CAR) Negroid populations (0.77, 131/170 OCA2 chromosomes; 0.79, 11/14; 0.33, 4/12, respectively). Normally pigmented individuals from different African countries were also tested. The deletion mutation was found at a frequency of 0.013 (10/780) in the normally pigmented southern African Negroid population and at a lower frequency in individuals from central Africa (0.002; 2/834), including individuals from Zambia, Cameroon, Zaire and the CAR. The study confirms the African origin of this deletion allele. Haplotype analysis suggests that the deletion mutation probably occurred only once and that it arose before the divergence of these African populations, which is estimated to be about 2000-3000 years ago. The unusually high frequency of OCA2 mutations, in particular the 2.7-kb deletion, suggests some selective agent or genetic drift.

Africa South of the Sahara↗

Audit in radiation therapy: long-term survival and cost of treatment.

In order to determine the cost of radiation treatment and the survival rate of a cohort of patients treated in a 6-month period in 1988, estimates of the capital and recurrent costs of this service were made for the calendar year 1988, expressed as $A(1988). Data collected prospectively included workload statistics, including number of attendances, field treated and complexity of treatment. Patient and tumour-related data included tumour site, intent of treatment and survival. The survival rate of patients during this period was determined in June 1995. The cost per field in 1988 was estimated at $A44.32. The 1988 costs of courses of definitive, adjuvant and palliative radiation therapy were estimated at $A2545, $A2482 and $A929, respectively. The major contributor to the cost was salaries and consumables within the Radiation Oncology Department (81.6%), with capital costs accounting for 13.5%, overheads accounting for 4.5% of the costs and planned admissions accounting for 0.2%. The median survival time of 580 patients with malignant disease treated during this period in 1988 was 12.4 months. The overall 5-year survival rate was 27%. For 105 patients treated definitively with radiation therapy, the median and 5-year survival rate figures were 26.0 months and 40%. For 149 patients treated with adjuvant radiation therapy, the 5-year survival rate was 62% (median survival rate not reached). For 279 patients treated palliatively, median and 5-year survival rate figures were 5.2 months and 3%. The cost per month of survival for all patients with malignancy was $A67, the figures for definitive, adjuvant and palliative treatments being $A74, $A48 and $A105, respectively. A sensitivity analysis indicated that these figures were robust. The cost of radiation treatment per field was comparable to reports for other centres and emphasizes the utility of radiation therapy as a cost-effective cancer treatment modality. With increasing pressure on treatment facilities in the public sector, further cost/benefit analysis is required to optimize the use of restricted resources.

Cohort Studies↗

Clinical audit in radiation oncology: results from one centre.

This study aims to determine workload statistics and to document patterns of fractionation in a single centre in two time periods separated by 4 years. Patient, tumour and treatment-related data were collected for courses of radiation treatment that were commenced within two 6-month periods in both 1988 and 1993. In both time periods, 45-49% of patients were treated with curative intent. Of these, one-third were irradiated definitively and two-thirds in an adjuvant setting. Most of the remainder were treated with palliative intent. A few were treated for non-neoplastic conditions. The re-treatment rate in 1993 was 13%. In both time periods, breast and lung tumours represented approximately 20% each of the total treatment courses. Skin, head and neck, gynaecological, urological and haematological primary tumours accounted for 5-10% each. Treatment intents differed markedly for different primary sites. For example, in 1993 65% of patients with breast primaries were treated curatively compared with 6% of patients with lung primaries. Treatment schedules for curative intent were similar in both time periods and for the majority of treatment sites. Median fraction numbers were 25 (excluding skin primaries), reflecting conventional daily fractionation. Treatment schedules for palliation showed greater variation and there was a trend towards shorter treatment courses in 1993. For palliative treatment of bone, brain and lung, from either primary or metastatic disease, treatment schedules with 10-15 fractions were used most frequently in 1988. In 1993, however, the majority of patients received 1-5 fractions. In 1993, the breakdown of techniques according to treatment intent showed that for treatment with curative intent, single, parallel opposed and more complex field arrangements were used in 27% (includes skin primaries), 12% and 61% of treatment courses, respectively, compared with 29%, 59% and 12%, respectively, for palliative treatment courses. In 1993, one-third of patients receiving radiation treatment lived in the local health area. Patients living in areas with rural postcodes were more likely to receive palliative irradiation and had a higher incidence of melanoma than patients living in areas with Sydney metropolitan postcodes. As approximately 50% of patients were treated with palliative intent, changes in the fractionation patterns used can alter significantly the utilization and availability of megavoltage equipment. However, any reduction in attendances caused by hypofractionation for palliation may be offset by the trend to use hyperfractionation for curative treatments. The data support the hypothesis of reduced availability and use of radiation therapy in patients with cancer from rural areas.

Adolescent↗

Radiosensitization of mouse skin by oxygen and depletion of glutathione.

PURPOSE: To determine the oxygen enhancement ratio (OER) and shape of the oxygen sensitization curve of mouse foot skin, the extent to which glutathione (GSH) depletion radiosensitized skin, and the dependence of such sensitization on the ambient oxygen tension. METHODS AND MATERIALS: The feet of WHT mice were irradiated with single doses of 240 kVp x-rays while mice were exposed to carbogen or gases with oxygen/nitrogen mixtures containing 8-100% O2. The anoxic response was obtained by occluding the blood supply to the leg of anesthetized mice with a tourniquet, surrounding the foot with nitrogen, and allowing the mice to breathe 10% O2. Further experiments were performed to assess the efficacy of this method to obtain an anoxic response. Radiosensitivity of skin was assessed using the acute skin-reaction assay. Glutathione levels were modified using two schedules of DL-buthionine sulphoximine (BSO) and diethylmaleate (DEM), which were considered to produce extensive and intermediate levels of GSH depletion in the skin of the foot during irradiation. RESULTS: Carbogen caused the greatest radiosensitization of skin, with a reproducible enhancement of 2.2 relative to the anoxic response. The OER of 2.2 is lower than other reports for mouse skin. This may indicate that the extremes of oxygenation were not produced, although there was no direct evidence for this. When skin radiosensitivity was plotted against the logarithm of the oxygen tension in the ambient gas, a sigmoid curve with a K value of 17-21% O2 in the ambient gas was obtained. Depletion of GSH caused minimal radiosensitization when skin was irradiated under anoxic or well-oxygenated conditions. Radiosensitization by GSH depletion was maximal at intermediate oxygen tensions of 10-21% O2 in the ambient gas. Increasing the extent of GSH depletion led to increasing radiosensitization, with sensitization enhancement ratios of 1.2 and 1.1, respectively, for extensive and intermediate levels of GSH depletion. In mice exposed to 100% O2, a significant component of skin radiosensitivity was due to diffusion of oxygen directly through the skin. Pentobarbitone anesthesia radiosensitized skin in mice exposed to 100% O2 by a factor of 1.2, but did not further sensitize skin in mice exposed to carbogen. CONCLUSIONS: Glutathione levels and the local oxygen tension at the time of irradiation were important determinants of mouse foot skin radiosensitivity. The extent to which GSH levels altered the radiosensitivity of skin was critically dependent on the local oxygen tension. These results have significant implications for potential clinical application of GSH depletion.

Animals↗

Patterns of fractionation for palliation of bone metastases.

The patterns of fractionation used to treat bone metastases in a single centre in two time periods were determined. Clinical audit was carried out, for two periods of 6 months each, in 1988 and 1993. Data recorded included patient, tumour and treatment variables. Palliation of bone metastases represented 40% and 44% of palliative treatment courses, and 20% and 21% of total treatment courses, respectively, in both time periods. Shorter treatment schedules were used in 1993 compared to 1988, with mean fraction numbers of 6.4 versus 8.5, respectively (P < 0.001). This reduction in fraction numbers occurred for the common primary tumour sites. In 1993, the mean numbers of fractions used were related to the primary tumour site (7.8 fractions for breast, 5.0 for lung, 6.7 for melanoma, 6.4 for other primary sites, P = 0.05), the treatment site (7.3 fractions for weight-bearing bones, 4.0 for non-weight-bearing bones, P < 0.001) and patient address (6.0 fractions for city postcode vs 7.8 for country postcode, P = 0.02). Treating radiation oncologist (5.7-7.8 mean fractions, P = 0.06) and patient age (P = 0.56) were not significant factors for the number of fractions used. It is likely that there were multiple causes for a reduction in the number of fractions used to treat bone metastases, including the results of clinical trials and increasing pressure to optimize the use of scarce resources. However, patients who may have a better prognosis (breast primary) and those with metastases in weight-bearing bones continued to receive longer treatment schedules.

Analysis of Variance↗

The evolving role of radiation therapy in paediatric oncology, Philadelphia, USA, 19-21 January 1995.

A summary of a conference reviewing recent developments and changes in the use of radiation therapy in paediatric oncology is reported. Although the use of radiation therapy has resulted in improved cure rates, the long-term complications of radiation in a paediatric population are recognised. More intensive systemic therapy and the increasing availability of prognostic data, including biological markers to tailor therapy to the individual patient, has resulted in a more selective use of radiation therapy. Changes in the management of specific tumour types are discussed.

Child↗

An intragenic deletion of the P gene is the common mutation causing tyrosinase-positive oculocutaneous albinism in southern African Negroids.

Tyrosinase-positive oculocutaneous albinism (OCA2), an autosomal recessive disorder of the melanin biosynthetic pathway, is the most common recessive disorder occurring in southern African Bantu-speaking Negroids, with an overall prevalence of 1/3,900. The OCA2 gene, P, has been mapped to chromosome 15q11-q13, and recently alterations in the P gene have been identified in OCA2 individuals. An intragenic deletion has been described and proposed to be of African origin because of its occurrence in four unrelated African American OCA2 individuals and in two individuals, one from Zaire and the other from Cameroon. This study shows that the intragenic deletion is a common cause of OCA2 in southern African Negroids (114/146 [.78]; OCA2 chromosomes) and is associated with one common haplotype (43/55 [.78]; OCA2 chromosomes), confirming the African origin of this allele. On the basis of haplotype data, it would appear that at least seven additional, less frequent OCA2 mutations occur in this population.

Albinism, Oculocutaneous↗

Beta/A4-evoked degeneration of differentiated SH-SY5Y human neuroblastoma cells.

beta/A4 peptides are known to induce neurodegeneration in cultures of rat brain cells and rat neural cell lines (Yankner et al: Science 250:279-282, 1990; Behl et al: Biochem Biophys Res Commun 186:944-950, 1992). The current data show that these peptides induce similar neurodegeneration in SH-SY5Y neuroblastoma cells, extending characterization of beta/A4 toxicity to a human nerve cell line. Human SH-SY5Y cells respond to aggregated beta/A4 with changes in cell shape, membrane blebbing, antigenic modification, loss of attachment to the substrate, and cell death. beta/A4 peptides require aggregation for maximum toxic effects, as cellular degeneration is evoked by aggregated beta/A4 1-42 and 4-41 cysteine but not by monomeric beta/A4 1-40. Aged (pre-aggregated) beta/A4 1-40 also evoked neurodegeneration. Antigenic changes comprise upregulation of Alzheimer's-type tau epitopes, recognized by the PHF-1 and Alz-50 monoclonals. These particular changes in tau support the connectivity between this in vitro model and mechanisms leading to neurodegeneration in Alzheimer's disease. A significant feature of the SH-SY5Y response is that cells must be differentiated before they become sensitive to the degeneration evoked by beta/A4. Signaling pathways leading to beta/A4-evoked neurodegeneration thus are under experimental control, becoming complete only when proliferating cells withdraw from the cell cycle and develop a postmitotic phenotype.

Alzheimer Disease↗

Treatment of early carcinoma of the vocal cords by radiotherapy.

A total of 145 patients with early carcinoma of the vocal cords (T1,2N0) were treated by radiotherapy from 1979 to 1989. Survival and local control data were available for 135 and 127 patients, respectively. The respective 5 and 10 year results for overall survival were 75 and 68%. The 5 and 10 year probabilities of local control by radiotherapy were 89 and 86%, respectively, for T1 tumours and 70% at both time intervals for T2 tumours. Tumour recurrence following radiotherapy was documented in 18 of 127 patients. Tumour stage predicted significantly for local control, with recurrence rates for T1 and T2 tumours of 11 and 27%, respectively (P = 0.02). There was a higher proportion of recurrences for total radiation doses < or = 6200 cGy (17%) compared with > 6200 cGy (8%), but the difference was not statistically significant. Increasing duration of treatment was related significantly to increased recurrence for T2 (P = 0.01), but not T1, tumours. Most recurrences (60%) were salvaged successfully by laryngectomy. Three patients required laryngectomy for laryngeal oedema without recurrent tumour; all had been treated using a large field size (7 x 6 cm). There were 20 metachronous tumours, including five lung and two head and neck tumours. These results are similar to previous reports and confirm that radiotherapy is very effective for early glottic cancer, with high local control rates and effective salvage if local recurrences are recognized early.

Adult↗

The effect of BW12C on the radiosensitivity and necrosis of murine tissues and tumours.

BW12C is a drug that has the potential to induce normal tissue and tumour hypoxia by binding to haemoglobin, increasing its affinity for oxygen and thereby reducing oxygen availability to tissues. Initial results suggested that BW12C administration caused significant radioprotection of normal tissues and induced tumour necrosis, but variable results have been reported subsequently. This work was carried to extend the range of observations concerning the ability of BW12C to radioprotect normal tissues and tumours and to induce necrosis of tumours of the mouse. BW12C was administered as 70 mg/kg i.v. 15 min before irradiation of jejunum in CBA mice and of foot skin in WHT mice with single doses of 240 kVp X-rays while mice breathed gases of varying oxygen tensions. The radiosensitivities of these tissues were assessed by the crypt survival assay and the acute skin reaction, respectively. The radiosensitivity of CaNT tumours to single fraction irradiation was assessed by the regrowth delay assay following administration of single or multiple doses of BW12C at varying times to air-breathing CBA mice. The radiation response was compared to the radiosensitivity of clamped tumours. The effect of BW12C alone on tumours was assessed by regrowth delay and histological examination for necrosis. BW12C did not change the radiosensitivity of jejunal crypts irradiated while mice breathed air or 10% O2, or of foot skin when mice breathed 12% O2. BW12C protected foot skin by a factory of 1.1 when mice breathed air. Single or multiple doses of BW12C did not influence the radiosensitivity of CaNT tumours, although marked radioprotection could be induced by clamping the tumours during irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗