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Biomedical subjects

B Curran

Publications and source records attributed to B Curran.

At least 19 recordsLinked to original sources
PubMed1999

Dosimetric verification of a commercial inverse treatment planning system.

A commercial three-dimensional (3D) inverse treatment planning system, Corvus (Nomos Corporation, Sewickley, PA), was recently made available. This paper reports our preliminary results and experience with commissioning this system for clinical implementation. This system uses a simulated annealing inverse planning algorithm to calculate intensity-modulated fields. The intensity-modulated fields are divided into beam profiles that can be delivered by means of a sequence of leaf settings by a multileaf collimator (MLC). The treatments are delivered using a computer-controlled MLC. To test the dose calculation algorithm used by the Corvus software, the dose distributions for single rectangularly shaped fields were compared with water phantom scan data. The dose distributions predicted to be delivered by multiple fields were measured using an ion chamber that could be positioned in a rotatable cylindrical water phantom. Integrated charge collected by the ion chamber was used to check the absolute dose of single- and multifield intensity modulated treatments at various spatial points. The measured and predicted doses were found to agree to within 4% at all measurement points. Another set of measurements used a cubic polystyrene phantom with radiographic film to record the radiation dose distribution. The films were calibrated and scanned to yield two-dimensional isodose distributions. Finally, a beam imaging system (BIS) was used to measure the intensity-modulated x-ray beam patterns in the beam's-eye view. The BIS-measured images were then compared with a theoretical calculation based on the MLC leaf sequence files to verify that the treatment would be executed accurately and without machine faults. Excellent correlation (correlation coefficients > or = 0.96) was found for all cases. Treatment plans generated using intensity-modulated beams appear to be suitable for treatment of irregularly shaped tumours adjacent to critical structures. The results indicated that the system has potential for clinical radiation treatment planning and delivery and may in the future reduce treatment complexity.

Algorithms↗
PubMed1999

Theoretical considerations of monitor unit calculations for intensity modulated beam treatment planning.

A treatment planning system to compute intensity modulated radiotherapy (IMRT) treatments using inverse planning was investigated. The system was designed to optimize the intensity patterns required to treat a specified target volume with specified normal structure constraints. A beam model that uses the convolution of pencil beams was used to compute the dose distributions. A multileaf collimator leaf-setting sequence intended to produce the intensity pattern was computed along with the monitor units required to deliver each of a number of fixed-gantry modulated fields. Computer calculations are commonly verified using an independent manual procedure. It is difficult to calculate treatment delivery monitor units for this variant of IMRT using manual methods. Since manual calculations are not feasible, it is important both to understand and to verify the calculation of treatment monitor units by the planning system algorithm. A formal analysis was made of the dose calculation model and the monitor unit calculation embedded in the algorithm. Experimental verification of the dose delivered by plans computed with the methodology demonstrated an agreement of better than 4% between the dose model and measurements.

Algorithms↗
PubMed1999

Combination of pressure and velocity parameters in the non-invasive diagnosis of aorto-iliac disease.

Three different femoral artery flow velocity parameters in combination with segmental pressure measurements were evaluated for their respective diagnostic value in identifying the presence or absence of hemodynamically significant aorto-iliac disease. A total of 60 patients (119 legs) were examined both non-invasively and with arteriography. Doppler flow velocities were recorded using a 5-MHz CW Doppler velocity metering system. Of the three parameters used (peak velocity, decay time and deceleration), a decay time of 220 ms yielded the most practical discriminant value. The accuracy increases when in addition the upper thigh/arm pressure ratio values are considered. The results indicate that the combination of femoral artery decay time with the upper thigh/arm pressure index provides a simple and accurate non-invasive screening method to confirm or rule out aorto-iliac disease. This helps to determine whether the patient is a candidate for arteriography and for potential surgical intervention.

Aorta↗
PubMed1997

Determination of testicular function after torsion by DNA flow cytometry of serial fine-needle aspirates.

OBJECTIVE: To determine the efficacy of DNA flow cytometric analysis of testicular percutaneous fine-needle aspirates in the assessment and follow-up of testicular function after torsion, and to determine the relationship between the duration of torsion and testicular injury. MATERIALS AND METHODS: Three groups of 15 adult rats underwent a 720 degrees torsion, with fixation of the mesorchial ligament, for 1, 3 or 5 h. Bilateral aspirations, performed 7, 21 and 35 days after torsion were examined by flow cytometry. Testes were harvested and evaluated histologically using Johnsen's scoring. RESULTS: Irreversible testicular injury occurred in all three groups of rats, with loss of function after 1 h and loss of viability after 3 and 5 h. The results from flow cytometry suggested significant contralateral testicular injury (P < 0.025) but this was not supported by the histological evaluation. There was a strong correlation between the testicular function assessed by flow cytometry and by Johnsen's scoring of histological specimens (r2 = 0.95). CONCLUSION: The assessment of testicular aspirates by flow cytometry allows testicular function to be followed after torsion in rats, and potentially in humans. Using DNA flow cytometry, the temporal course of the twisted testis in the adult rat was determined; contralateral testicular injury following the reversal of torsion could not be excluded.

Animals↗
PubMed1997

Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia.

We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (n = 16) and also from normal cervix (n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.

Epithelium↗
PubMed1997

Identification of Euro-Americans, Afro-Americans, and Amerindians from palatal dimensions.

Seven measurements were taken on 414 Euro-American, Afro-American, and Amerindian palates in an attempt to evaluate differences in dental arcade shape among these three groups. Width measurements across the palate at the first incisor, canine, second premolar, and second molar were taken directly on the dental arcade. The distances along the sagittal plane from the front of the palate to the level of these teeth were calculated from measurements taken between the right central incisor and the canine, second premolar and second molar. Discriminant functions computed from the measurements properly classified palates by group 66.0% of the time if sex is unknown. If sex is known to be male, other functions properly classified 65.7% of the sample; for sex known to be female 72.0% correct classification was achieved. Because these percentage are more than twice that expected from probability theory alone, it is concluded that the seven measurements are useful in determining ethnic group.

Black or African American↗
PubMed1996

An image analysis study of DNA content in early colorectal cancer.

The DNA content of 168 consecutive T3,N0,M0 (Dukes' B, Astler-Coller B2) colorectal cancers was studied using image analysis on formalin-fixed paraffin-embedded tissues. 72 cases (43%) were classified as diploid and the remaining 96 (57%) as non-diploid. After a median follow-up period of 6.7 years, a significant survival advantage was found for diploid compared with non-diploid cases (logrank test; P = 0.008). The long-term (8 year) survival rate was 70% for diploid and 46% for non-diploid tumours. Subgroup analysis showed that the survival advantage conferred by tumour diploidy was greatest in large (> or = 5 cm) cancers and was found both in colonic and rectal cancer cases. These data indicate that tumour ploidy status measured by image analysis might be useful in determining risk of colorectal cancer recurrence and death in patients following resection of early colorectal cancer.

Adult↗
PubMed1996

Proliferation indexes--a comparison between cutaneous basal and squamous cell carcinomas.

AIMS: To compare differences in cell proliferation indexes and apoptotic indexes between cutaneous basal and squamous cell carcinomas, in an attempt to suggest an explanation for the differences in their biological behaviour. METHODS: Forty cases of cutaneous basal cell carcinoma (BCC) and 40 cases of moderately and well differentiated squamous cell carcinoma (SCC) were retrieved from the archives. Sections, 4 microns thick, were cut from formalin fixed, paraffin wax embedded tissue in each case and stained with haematoxylin and eosin. These were then examined for mitotic and apoptotic figures per 1000 cells. Sections from the same cases were also immunostained with the mouse monoclonal antibody Ki67 (MIB1); positive nuclear staining was counted per 1000 cells. RESULTS: No significant differences were found between the mitotic indexes and apoptotic indexes in these tumours. There was, however, a significant difference in Ki67 (MIB1) staining, with greater staining in the squamous cell carcinomas. CONCLUSION: Estimation of the mitotic and apoptotic indexes did not reveal any differences between these two tumour types. The proliferation indexes, assessed by Ki67 immunostaining, did differ. This may be one of the factors underlying the more aggressive behaviour of SCC.

Apoptosis↗
PubMed1996

DNA ploidy, expression of p53 protein and metastatic behaviour of gastric carcinoma.

DNA ploidy of 57 gastric carcinomas with metastases (12 liver, 1 adrenal, 4 ovary and 48 lymph node) were measured by flow cytometry. DNA anueploidy was significantly related to liver metastases: 9 out of 12 gastric carcinomas with liver metastases were anueploid (75%) as compared to 13 out of 45 (28.8%) of cases without liver metastases (P < 0.01); the one gastric carcinoma with adrenal metastasis was also anueploid. DNA ploidy was not related to ovarian or lymph node metastases. Another interesting finding was that all of 3 gastric carcinomas with liver metastases which showed a diploid DNA pattern, expressed p53 protein, while all of 3 carcinomas with liver metastases but no p53 protein expression were anueploid. The expression of p53 protein was not related to ovarian metastases. The results suggested that an anueploid DNA pattern and the expression of p53 protein are both objective markers valuable in predicting high risk potential of metastases to the liver, and that the combined detection of these markers can be a most useful method in the follow-up of patients with gastric carcinoma in detecting those at high risk of developing metastases following surgical resection. Also the poorer prognosis of patients with gastric carcinoma showing an anueploid DNA pattern may be related to the development of distant organ metastases through the blood vascular system. Furthermore, the clone of gastric carcinoma cells which accumulate p53 protein or show an anueploid DNA pattern may have a causative role in the development of liver (& adrenal) metastases.

Adenocarcinoma↗
PubMed1995

DNA ploidy status in 84 ocular melanomas: a study of DNA quantitation in ocular melanomas by flow cytometry and automatic and interactive static image analysis.

Deoxyribonucleic acid (DNA) ploidy was quantified in 84 ocular melanomas (median follow-up, 11-years) by flow cytometry, CAS 200 interactive image analysis, and Pathology Image Processing Environment (PIPE; Department of Quantitative Pathology, Free University, Amsterdam, The Netherlands) automatic image analysis (75). Overall, 32.1% of the melanomas were aneuploid, 2.3% were tetraploid, and 66.6% were diploid. Pathology Image Processing Environment analysis estimated DNA ploidy in 12 tumors that were unprocessable by flow cytometry. Of 10 tumors that were diploid by flow cytometry, PIPE detected stemline aneuploidy in five and some aneuploid cells in five more. Seven tumors were aneuploid by PIPE but diploid by CAS 200, five of which contained occasional DNA aneuploid cells on the CAS 200 histograms. Pathology Image Processing Environment analysis quantified tumor samples with an average of 500 (250 to 1,050) cells in less than 10 minutes. All cells classified as spindle A according to the Callender system (more than 10,000) were diploid. Spindle B and epithelioid cells occupied both diploid and aneuploid peaks on the DNA histograms. Dioxyribonucleic acid variables did not correlate with established prognosticators, such as Callender cell type, largest tumor dimension, or glaucoma, nor did they reach significance by univariate and multivariate analyses. The value of these findings as a diagnostic support in uveal melanoma, particularly in combination with fine needle aspiration biopsy, is discussed.

DNA, Neoplasm↗
PubMed1994

Toe pressure determination by audiophotoplethysmography.

PURPOSE: The purpose of this study was to evaluate the performance of audiophotoplethysmography as a modality to measure toe pressure without the requirement of a recorder. METHOD: A portable photoplethysmograph with an audio output was used to determine toe pressures, and the results were compared with those obtained by a commercial photoplethysmograph with a recorder. RESULTS: Thirty-one measurements in control subjects and 62 measurements in patients with arterial occlusive disease were performed. The average toe pressure recorded with oscillography with standard photoplethysmography was 103.5 mm Hg +/- 14.7 SD and 95.9 mm Hg +/- 13.4 SD with audio-photoplethysmography. In the patient group the pressure recorded with a commercial photoplethysmograph was 65.3 mm Hg +/- 34.9 SD compared with 61.6 mm Hg +/- 34.8 SD obtained with audio-photoplethysmography. The difference in both groups was insignificant, and the correlation between both methods was very good. CONCLUSION: A portable hand-held photoplethysmograph equipped with an audio output was used to measure toe pressure in control subjects and in patients with arterial occlusive disease. The results have been compared with the oscillometric method by a standard commercial photoplethysmograph connected to a recorder. The correlation was very good in the control and patient groups, and the difference between both methods was below the level of statistical significance. The fact that no recorder is needed may help in introducing toe pressure measurement into everyday office diagnostic practice.

Arterial Occlusive Diseases↗
PubMed1994

C-erbB-2 immunostaining: problems with interpretation.

AIMS: To assess the consistency and reproducibility of assessment of c-erbB-2 immunostaining, and to examine some of the problems relating to inter- and intraobserver variability in the documentation of positive staining; to profile the spectrum of cytoplasmic and membranous staining in a wide range of tumour types. METHODS: A total of 283 neoplasms were examined for immunohistochemical expression of the c-erbB-2 oncoprotein. Three independent observers were required to assess intensity both of membrane and cytoplasmic staining on a three point and then a four point scale. Extent of positive staining was also assessed on a two point scale. A minimum of two weeks elapsed between assessments using the differing scales. RESULTS: Positive membrane staining was documented by one or more observers in 16.6% of tumours examined. This positivity was largely restricted to bladder, renal, and breast tumours. The overall level of disagreement as to the presence or absence of membranous staining was 11.3%. Cytoplasmic staining was identified in 55.5% of tumours studied. The level of disagreement as to the presence or absence of cytoplasmic staining was 26.5%. CONCLUSIONS: Intraobserver variability was minimal, indicating that each pathologist was adhering to internal reproducible standards. Interobserver variability was greater, indicating that the interpretation of c-erbB-2 immunostaining may require set guidelines. It is suggested that assessment should be referenced to a standard positive control, that a three tier system for grading of intensity and a two tier system for grading of extent should be adopted, and that the evaluation should be agreed by at least two pathologists. The presence of cytoplasmic staining should continue to be routinely recorded until its biological role and clinical implications are fully understood.

Biomarkers, Tumor↗
PubMed1993

Deoxyribonucleic acid ploidy studies in choroidal melanomas.

In several tumors of different organ sites, the amount of DNA in a cell (ploidy) is associated with malignancy. We performed DNA quantitation in 21 choroidal melanomas and compared flow cytometry with image analysis in 11 of these melanomas. We modified our preparation technique to overcome problems with pigment and control cell populations in the image analysis group. Fifteen tumors were diploid and two tumors were tetraploid. Four tumors were unprocessable by flow cytometry, but two of these tumors were diploid by image analysis. Image analysis also detected tetraploidy in two tumors that were diploid by flow cytometry. During image analysis, cells were classified according to the Callendar classification and histograms were plotted for each cell type. All spindle A cells were diploid and most tetraploid peaks were formed by epithelioid cells. The use of image analysis on small samples of choroidal melanomas may be of value both in confirmation of diagnosis and prognosis of these lesions, and perhaps therapeutically, for example, in the monitoring of radiation treatment.

Choroid Neoplasms↗
PubMed1993

c-myc expression in renal carcinoma: correlation with clinical parameters.

There is evidence that c-myc is expressed in renal carcinomas and that it is associated with histological grade. This study reports on the clinical correlations of oncogene expression and clinical features of the disease. Tissue sections from 97 patients (95 primary and 12 secondary cancers) were immunostained with a c-myc oncoprotein antibody. The tumours were scored for extent and intensity of nuclear and cytoplasmic staining. Ninety patients were suitable for follow-up study. High levels of expression correlated significantly with increasing T category and nuclear grade, as well as with venous invasion. No correlation with nodal involvement, the presence of metastases, tumour architecture or cell type was found. The extent of nuclear staining was related to survival (although not to recurrence), but in a multivariate analysis did not provide independent prognostic information. It was concluded that semiquantitative assessment of levels of c-myc oncoprotein does not provide clinically useful prognostic information.

Adult↗
PubMed1993

Ploidy and prognosis in renal carcinoma.

The value of tumour ploidy status as a prognostic indicator in renal carcinoma is disputed. In this retrospective study the DNA content of 90 primary and 10 secondary renal cell carcinomas was measured using flow cytometry. Data on recurrence and survival were available in all cases. Tumours were staged according to the TNM system and histological grade was based on nuclear morphology. Formalin-fixed, paraffin-embedded material was processed using standard techniques. Multiple samples were examined in 19 cases. Of the primary tumours, 52 were diploid, 24 were aneuploid and 6 were tetraploid; 8 patients had uninterpretable histograms. Ploidy of the secondary tumours was similar to that of their respective primaries. Aneuploidy correlated with higher grade but not with TNM category and, although associated with an increased risk of death, did not provide independent prognostic information. Heterogeneity of ploidy was found in 6 of the 19 cases where more than 1 sample was assessed. It was concluded that tumour DNA content in renal carcinoma is weakly linked to outcome, is subject to sample error and does not provide accurate prognostic information as a single independent variable.

Adult↗
PubMed1993

Comparison of flow and static image cytometry in the determination of ploidy.

AIMS: To compare the efficiency of flow cytometry and computed image cytometry; and to see if a reliable set of guidelines regarding interpretation of histograms could be drawn up. METHODS: The two methods were applied to a series of 111 formalin fixed renal cell carcinomas. Data generated by both methods were compared. RESULTS: The methods agreed in 85 cases. Hypodiploidy was detected by computed image cytometry in seven cases in which flow cytometry had shown only an aneuploid peak. Aneuploidy in seven in which the corresponding flow cytometry histogram was diploid. There was an overlap in the second peak proportions on flow cytometry histograms between those classed as diploid or tetraploid by computed image cytometry. In six cases the flow cytometry histograms had unacceptably high coefficients of variation and in all of these cases computed image cytometry demonstrated aneuploidy. CONCLUSIONS: Computed image cytometry is particularly useful for clarifying difficult areas in flow histograms--specifically, high coefficients of variation, high G2M phase, as well as possible near diploid aneuploidy and hypodiploidy.

Carcinoma, Renal Cell↗
PubMed1993

Partial hydatidiform mole: a common but underdiagnosed condition. A 3-year retrospective clinicopathological and DNA flow cytometric analysis.

This retrospective study reports the incidence of hydatidiform mole in a population of 19,457 pregnancies over a 3-year period. During the study period all "products of conception" from first and second trimester abortions were referred for pathological examination. Coded histologic sections were reviewed using the published histologic criteria for hydatidiform mole. Ploidy was estimated by DNA flow cytometry. Clinical data were retrieved from maternal case notes. Thirty-eight cases were confirmed as hydatidiform mole, 10 (26%) as complete mole, and 28 (74%) as partial mole. Twenty-three cases of partial mole (88%) were triploid, and nine of 10 complete moles were diploid. The incidence of hydatidiform mole was 1:512 pregnancies, (complete mole, 1:1,945; partial mole, 1:695). Only one case (3.5%) of partial mole was suspected clinically. One case of persistent gestational trophoblastic disease occurred following a complete mole. No sequelae were encountered following partial mole. We conclude that hydatidiform mole is a common condition and the majority of cases are partial moles. Quantitatively imprecise morphologic criteria contribute to the inaccuracy in reporting of partial mole; analysis of ploidy is useful in the evaluation of problem cases. Follow-up of partial mole is warranted because its true biological potential is as yet unclear.

Abortion, Spontaneous↗