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Biomedical subjects

R D Hunter

Publications and source records attributed to R D Hunter.

At least 55 records · Page 3Linked to original sources
PubMed1995

Serum tumour markers in carcinoma of the uterine cervix and outcome following radiotherapy.

A study was made of the prognostic value of measurements of pretreatment serum marker levels in patients with carcinoma of the uterine cervix undergoing radiotherapy. The markers studied were carcinoma antigen 125 (CA125), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA). The levels of all three markers increased with disease stage. In a univariate analysis stratifying patients according to either median values or cut-off levels representing the top of the normal range, pretreatment levels predicted patient survival (follow-up times 1-4 years). In a multivariate analysis, disease stage was the most important prognostic variable and, after allowing for stage, only CA125 was a significant independent predictor of treatment outcome. These data suggest that, in carcinoma of the cervix treated with radiotherapy, pretreatment measurements of CA125, but not SCC and TPA, may have a role to play in defining prognosis.

Antigens, Neoplasm↗
PubMed1995

Reevaluation of the effectiveness of environmental designs to reduce robbery risk in Florida convenience stores.

Prevention of intentional injuries to convenience store workers has focused on prevention of robbery. Data from a cross-sectional study of the effectiveness of environmental designs to deter robbery in Florida convenience stores were reanalyzed in order to determine the effect of confounding from local crime risk factors and other environmental designs on robbery rate. Results of this reanalysis were applied to a review of the literature. Of 14 store design factors and 5 local crime risk factors considered, concealed access/escape routes, cash register located at the back or the side of the store, high county crime rate, and high county population size were significantly associated with increased robbery rate. Poor cash handling policy was significantly related to a decreased robbery rate. Results also indicated that local crime factors and some environmental designs confound the relationship between other environmental designs and robbery rate. Conclusions from this reanalysis indicated that studies of the effectiveness of environmental designs to deter robbery must adjust for confounding. Although environmental design tends to be an effective robbery deterrent strategy, results from studies have been inconsistent as to the effectiveness of specific design factors. This inconsistency is partially explained by lack of adjustment for confounding from local crime risk factors and multiple environmental design factors. Areas for further research are discussed.

Crime↗
PubMed1994

Quantitation of endothelial cell specific protein E-9 employing a single monoclonal antibody in an indirect sandwich ELISA.

An indirect enzyme-linked immunosorbent assay is described for the quantitation of protein E-9 which is specifically expressed on human vascular endothelial cells. The assay capitalizes on the dimeric structure of the E-9 protein by utilizing a single monoclonal antibody as both the capture and detection reagent. Detection is achieved by conjugating the Mab with biotin and is followed by the addition of streptavidin peroxidase to provide high sensitivity. Bound activity is measured by enhanced chemiluminescence utilizing standard Amerlite chemistry. The optimised assay is reproducible and is highly sensitive. Using this assay it was possible to detect the presence of E-9 protein in tissue culture media of endothelial cells and in serum samples--in one case even at 1/100 dilution. In vitro, X irradiation resulted in a greater than two-fold increase (P < or = 0.005) in the level of E-9 protein in culture supernatants of human umbilical vein endothelial cells (HUVEC). There are potential applications for measurements of E-9 protein in body fluids and tissue extracts from patients with a vast variety of diseases characterised by vascular endothelial damage and/or activation.

Animals↗
PubMed1994

Irradiation of bovine aortic endothelial cells enhances the synthesis and secretion of sulphated glycosaminoglycans.

The effect of X-irradiation on the synthesis of heparan sulphate (HS) and chondroitin/dermatan sulphate (CS/DS) by bovine aortic endothelial cells (BAEC), was studied by measuring the incorporation of [35S]sulphate and [3H]glucosamine into newly synthesized glycosaminoglycan (GAG) chains. Medium extracts from irradiated cultures (5Gy) were found to contain approx. 130% more HS and 200% more CS/DS than unirradiated controls. Smaller increases were observed in cellular extracts, irradiated cultures (5Gy) containing approx. 60% more HS and 100% more CS/DS than unirradiated controls. Structural studies showed no significant changes occurred upon irradiation in either the amounts or distribution of N- and O-sulphate groups in the HS molecule. Values for N-sulphation of 41.1% control and 41.5% irradiated (5Gy) were obtained, the corresponding values for O-sulphation being 19.9% control and 20.2% irradiated. Isotope incorporation data indicated that sulphation of CS/DS may decrease after irradiation, however, analysis of chondroitin ABC lyase derived disaccharides showed no changes in the proportion of non-sulphated and O-sulphated disaccharides. The present study indicates that X-irradiation stimulates the synthesis and secretion of HS and CS/DS proteoglycans (PGs) by BAEC. This could be relevant to many features which are found to be indicative of radiation-induced damage.

Animals↗
PubMed1993

A monoclonal antibody detects heterogeneity in vascular endothelium of tumours and normal tissues.

A new murine monoclonal antibody (MAb), E-9, has been raised using tissue-cultured human umbilical vein endothelial cells. The antigen recognized by this MAb is a peptide of 170 kDa under non-reducing conditions and 96 kDa under reducing conditions. MAb E-9 showed marked heterogeneity in its distribution in various tissues. The antigen recognized by it was present in vascular endothelial cells of all tumours, foetal organs and in regenerating and inflamed tissues. It stained a few normal tissues. However, with the exception of tonsils, staining tended to be weak and limited to a few blood vessels, as revealed by double staining using pan-endothelial antibody (CD31) and antibody to von Willebrand factor, another marker of vascular endothelium. Surprisingly, blood vessels within the placental villi were completely negative. The function of the antigen recognized by MAb E-9 is not known, but its evaluation and use should increase our understanding of angiogenesis.

Adult↗
PubMed1993

Uptake and depuration of PCB 77, PCB 169, and hexachlorobenzene by zebra mussels (Dreissena polymorpha).

Zebra mussels (Dreissena polymorpha) were examined for their ability to take up and depurate hexachlorobenzene (HCB), 3,3',4,4'-tetrachlorobiphenyl (PCB 77), and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB 169) in the laboratory. The intent was to investigate response to acute exposure at high contaminant levels and to observe the time course of depuration. Tissue loads of all three compounds taken up from food increased rapidly and peaked after 10 (PCB 169), 14 (PCB 77), and 21 (HCB) days followed by rapid depuration to equilibrium levels. Peak tissue loads were 3.7, 3.4, and 3.6 micrograms/g for PCB 169, PCB 77, and HCB, respectively (wet weight basis). Equilibrium levels were approximately 1.0 microgram/g for both PCB 169 and HCB. Uptake rate of PCB 77 followed the order: sediment > food > water. Dreissena sampled from five Great Lakes field sites had tissue Aroclor loads ranging from 120 to 530 ng/g for Aroclor 1242 and 33 to 270 ng/g for Aroclor 1254 (wet weight basis). PCB 77 was detected at 1.9 ng/g at one site. Tissue levels for both Aroclors in Dreissena were approximately 10 times those of Lampsilis siliquoidea, a unionid bivalve to which they were attached. Where Dreissena reaches high densities, it is likely to play a significant role in contaminant dynamics.

Animals↗
PubMed1993

Intrinsic radiosensitivity and prediction of patient response to radiotherapy for carcinoma of the cervix.

The intrinsic radiosensitivity of cervical carcinoma has been measured using a soft agar clonogenic assay. All patients received radical radiotherapy alone with a minimum of 2 years post-treatment follow-up. Only women with stage I, II and III disease were included in the analysis. Values for cell surviving fraction at 2 Gy (SF2) were obtained for 88 tumours with an assay success rate of 73%. The 53 patients alive and well at the time of analysis had tumours with a mean SF2 that was significantly lower than the value from the 22 patients with locoregional failure (P < 0.01). Patients with radioresistant tumours (SF2 > 0.40, the median) had a significantly lower 3 year survival level than those with sensitive tumours (SF2 < or = 0.40) (P = 0.002). Also the frequency of local recurrence was higher (P = 0.001) whether these were central (P = 0.009) or peripheral (P = 0.046). Cell surviving fraction at 3.5 Gy was obtained for 46 tumours and the 3 year patient survival rate was significantly higher for those with SF3.5 values less than the median (P = 0.043). There was, however, no difference in the level of local recurrence (P = 0.24). The ability to grow in culture was not associated with significantly poorer patient survival (P = 0.56) or failure to control the primary disease (P = 0.17). While high colony forming efficiencies were associated with an increased rate of local recurrence (P = 0.029) they did not predict for overall patient survival (P = 0.32). These data suggest that, for cervical carcinoma treated with radical radiotherapy, intrinsic radiosensitivity is important in determining treatment outcome.

Adult↗
PubMed1993

Use of low-dose rate irradiation to measure the intrinsic radiosensitivity of human T-lymphocytes.

A comparison has been made of high (1.55 Gy min-1) and low dose-rate (0.0098 Gy min-1) irradiation in determining the intrinsic radiosensitivity of peripheral blood lymphocytes from normal individuals. Samples from 19 people were assessed using a limiting dilution assay and used to investigate the variability associated with evaluation of lymphocyte radiosensitivity after both high and low dose-rate irradiation. Repeat experiments on a single sample from one donor stored over a period of 6 months have been used to compare assay variability using the different dose-rates. Multiple samples taken from a single person over a period of 5 months were assayed at low dose-rate to assess intraindividual variation in measured in vitro radiosensitivity. At high dose-rate significant interexperimental variation in the measured parameters was demonstrated and, after allowing for this variability, no significant interindividual differences were found. At low dose-rate, sparing of cell kill was seen for all lymphocytes and led to an increase in the spread of data between individuals such that interindividual differences reached statistical significance for surviving fraction at 4 Gy, alpha (linear fit) and D with p < 0.004 for all parameters.

Cell Survival↗
PubMed1993

Use of an internal standard in comparative measurements of the intrinsic radiosensitivities of human T-lymphocytes.

A study has been made of the intrinsic radiosensitivity of peripheral blood lymphocytes from normal individuals. Cell survival following in vitro high (1.55 Gy min-1) and low (0.0098 Gy min-1) dose-rate irradiation was obtained for single lymphocyte samples from three individuals in six experiments. Despite wide interexperimental variability the ranking of intrinsic radiosensitivity for these individuals was reproducible. Further studies were carried out using low dose-rate irradiation only, on: (1) single lymphocyte samples from 18 people; (2) 14 samples taken on different occasions from one of these donors over a period of 5 months; and (3) a large store of lymphocytes from another individual. The latter was assayed in every experiment and served as an internal standard to which results could be normalized. In comparison with uncorrected values, the normalized results for the 14 samples from the single individual showed a reduction in the spread of data while those for the 18 different donors were unchanged. An analysis of variance was carried out on a larger data set of 38 measurements which included repeat assays on several of the samples (two samples from the multiply-sampled individual and five samples from other donors were assayed twice). In comparison with the uncorrected values, the normalized results showed a reduction in experimental variability such that the coefficient of variation (CV) for surviving fraction at 4 Gy for the multiple samples from a single individual decreased from 41 to 19%. In contrast, there was little change in the variation between 18 individuals with CVs of 56 and 62%, respectively, for uncorrected and normalized results. These data suggest that the use of an internal standard for the determination of the intrinsic radiosensitivity of individuals using peripheral blood lymphocytes should aid the development and evaluation of predictive tests for the radiotherapy of cancer.

Cell Survival↗
PubMed1992

Lack of association between in vitro clonogenic growth of human cervical carcinoma and tumour stage, differentiation, patient age, host cell infiltration or patient survival.

Biopsies from 117 patients with cervical carcinoma were studied using a clonogenic assay to assess in vitro growth. Successful colony growth was achieved in 84 tumours (72%) with a mean colony-forming efficiency (CFE), based on total viable nucleated cell counts, of 0.18 +/- 0.49% (+/- 1 standard deviation). There was a wide range of values, from 0.003-4.28%, with a coefficient of variation of 272%. The relationship between clinical features of cervical carcinoma and in vitro colony formation was investigated. No significant association was demonstrated between in vitro growth and either clinical stage (r = 0.02), tumour differentiation (r = -0.08) or patient age (r = -0.12). There was no significant difference in tumour grade between the group of tumours which failed to grow in culture and those which grew well (p = 0.70). In addition, there was no correlation between CFE and the degree of macrophage (r = 0.001), lymphocyte (r = 0.12), or granulocyte (r = 0.08) infiltration. There was no significant difference between CFEs of tumours from patients who had died and from those who were alive and well after a minimum of 2 years' follow-up after radiotherapy (p = 0.51). Ability to form colonies in agar was not associated with a worse prognosis (p = 0.49). Although CFE is an independent biological parameter, our results suggest that, for cervical carcinoma, it is not useful as a univariate prognostic factor.

Adenocarcinoma↗
PubMed1992

Carcinoma of the cervix: an analysis of prognostic factors, treatment and patterns of failure following Wertheims hysterectomy.

A clinicopathologic analysis of 70 patients treated by radiotherapy and/or chemotherapy following primary radical surgery has been undertaken. Clinical stage at presentation was IB (58 patients) and IIA (12 patients). Thirty-five patients (50%) had squamous carcinoma, 23 (33%) had adenosquamous carcinoma, 9 (13%) had adenocarcinoma and 3 (4%) had an undifferentiated neoplasm. The reasons for further treatment were: (i) pelvic lymph node metastases (PLNM), 35 (50%); (ii) inadequate central clearance (ICC), 13 (18%); (iii) recurrent disease (RD), 17 (24%); (iv) others, 5 (8%) cases. Sixty-seven patients had radiotherapy, one of whom also received adjuvant chemotherapy, three patients had chemotherapy alone, and 12 patients received chemotherapy for recurrence following radiotherapy. The 5-year survival in the above referral groups were: (i) 66%; (ii) 62%; (iii) 12%. The site of relapse following treatment was primarily pelvic in groups 2 (ICC) and 3 (RD) and extrapelvic in group 1 (PLNM). Of the histologic parameters studied the only factor of statistical significance in predicting outcome in this group who are recognized to have a generally poor prognosis was the presence of parametrial extension (P = 0.0066). Six cases (9%) developed complications following therapy, lymphoedema being the most common (66%).

Journal Article↗
PubMed1991

The antiemetic effect of granisetron in lower hemibody radiotherapy.

Radiotherapy-induced emesis is poorly controlled with existing antiemetics. 5-Hydroxytryptamine (5HT3) receptor antagonists are a new class of antiemetics which have been demonstrated to be effective in controlling cytotoxic-induced emesis. We have prospectively studied the antiemetic efficacy of the 5HT3 receptor antagonist granisetron in an open non-randomized efficacy and toxicity study, at two dose levels, in patients receiving lower hemibody radiotherapy for multiple bone metastases. Of the 22 patients studied, 13 patients received 20 micrograms/kg and nine patients 40 micrograms/kg of granisetron, administered as an intravenous infusion 1 h before radiotherapy. Radiotherapy was administered as a single exposure to the lower half body to a midline dose of 8 Gy. A complete response (no nausea or vomiting) was observed in 9/13 patients at the lower dose level and 6/9 patients at the higher level. No major adverse events were recorded. We conclude that granisetron is a well-tolerated and effective antiemetic agent in radiotherapy-induced emesis. Formal comparison with conventional antiemetic agents in this situation is required.

Aged↗
PubMed1990

Radiosensitivity testing of primary cervical carcinoma: evaluation of intra- and inter-tumour heterogeneity.

Biopsies from 89 patients with cervical carcinoma were studied using a clonogenic assay to obtain values for the surviving fraction at 2 Gy (SF2). Heterogeneity in intrinsic radiosensitivity was investigated by independently processing multiple biopsies from 18 tumors. No significant differences between intra-tumour SF2 values were demonstrated (p = 0.30). The results have shown that intra-tumour heterogeneity is not a limitation to radiosensitivity testing using the Courtenay-Mills assay. A wide range of values (0.13-0.97) for SF2 was obtained with a mean value of 0.47 +/- 0.18 (+/- 1 S.D., CV = 38%) for 52 squamous cell carcinomas and 0.59 +/- 0.27 for four adenocarcinomas. There were statistically significant differences between the individual tumours (p less than 0.001). From the analysis-of-variance of all the SF2 results it appears to be the surviving fractions below about 0.40 and those above about 0.7 which show significant differences in radiosensitivity between pairs of tumours (p = 0.05). Also 36% of the values of SF2 show significant differences from the mean SF2 of all tumours. The storage of tumour cell suspensions in liquid nitrogen improved the colony-forming efficiency (CFE) but it did not alter the radiosensitivity.

Analysis of Variance↗