Milling as a route to porous graphitic carbons from biomass.

This paper reports a simple way to produce porous graphitic carbons from a wide range of lignocellulosic biomass sources, including nut shells, softwood sawdust, seed husks and bamboo. Biomass precursors are milled and sieved to produce fine powders and are then converted to porous graphitic carbons by iron-catalysed graphitization. Graphitizing the raw (unmilled) biomass creates carbons that are diverse in their porosity and adsorption properties. This is due to the inability of the iron catalyst precursor to penetrate the structure of dense biomass material. Milling enables much more efficient impregnation of the biomass and produces carbons with homogeneous properties. Lignocellulosic biomass (particularly waste biomass) is an attractive precursor to technologically important porous graphitic carbons as it is abundant and renewable. This simple method for preparing the biomass enables a wide range of biomass sources to be used to produce carbons with homogeneous properties. This article is part of the theme issue 'Bio-derived and bioinspired sustainable advanced materials for emerging technologies (part 2)'.

Clinical outcome for chemoradiotherapy in carcinoma of the cervix.

AIMS: Two recent meta-analyses have shown a survival advantage for the addition of concurrent chemotherapy to radiotherapy in the treatment of cervical cancer. However, there is insufficient information available on late toxicity and few data from UK practice. The aims of this study were to examine treatment outcomes (survival and toxicity) in patients with cervical cancer treated with chemoradiation and to compare these with outcomes in patients treated with radiation alone. MATERIALS AND METHODS: Between July 2000 and December 2003, 75 patients with cervical cancer were treated with chemoradiation. Case notes were reviewed retrospectively. Acute and late toxicity were recorded, with late toxicity graded using the Franco-Italian glossary. The median age was 47 years. All patients were staged with examination under anaesthesia and magnetic resonance imaging scans. Forty-two patients were treated with concurrent chemoradiation alone and 33 patients were treated with a combination of neoadjuvant and concurrent chemoradiation. This was due to waiting list problems. The chemotherapy used was cisplatin 40 mg/m(2) weekly with radiotherapy, (the neoadjuvant dose was 60 mg/m(2) 3 weekly). External beam radiotherapy was given to the pelvis (40-45 Gy/20 fractions/4 weeks) followed by low dose rate brachytherapy (22.5-32.5 Gy to point A). Patients who were unable to have brachytherapy were given an external beam boost (15-20 Gy/8-10 fractions). RESULTS: The 3-year overall survival rate was 70%, with an estimated 5-year overall survival rate of 60%. The 3-year disease-free survival was 63.6%, with an estimated 5-year disease-free survival rate of 55%. Compared with the cohort of 183 patients from the Christie Hospital in a 1993 audit, there was a trend towards improved overall survival from 49 to 60% (P=0.06), which may become significant with longer follow-up. There were seven patients (9.3%) with grade 3 toxicity and no cases of grade 4 toxicity. In comparison with patients treated in the 1993 audit, the late toxicity rate has increased from 3.4 to 9.3%, but this was not statistically significant (P=0.14). CONCLUSION: There was a trend towards improved survival with concurrent chemoradiation in this cohort of patients that may become significant with longer follow-up.

Salvaging locoregional recurrence with radiotherapy after surgery in early cervical cancer.

AIMS: To determine the outcome and morbidity after radiotherapy for locally recurrent cervical cancer. MATERIALS AND METHODS: Women who presented with locally recurrent cervical cancer after surgery alone during 1985 and 1997 were identified from the hospital database. Data were collected and analysed to include the stage at first diagnosis, staging investigations before surgery, the surgical procedure, the indication for radiotherapy, the type of radiotherapy, morbidity and survival. RESULTS: In total, 130 women had radical external beam radiotherapy and/or intracavitary brachytherapy for locoregional recurrence during the defined study period. The 5-year disease-specific survival for the study population was 40.2%. Women who were treated for vault recurrence had a significantly better 5-year disease-free survival compared with women who developed nodal recurrence alone (55.4% vs 12.5%). This group of women also had a significantly slower rate of disease progression after radiotherapy than women with nodal recurrence (48.7% vs 87.5%, P=0.0001). CONCLUSION: Radical radiotherapy alone is able to salvage 55% of vaginal vault recurrences after surgery for cervical cancer with minimal late toxicity. Salvage rates in women with pelvic nodal recurrences are considerably lower. Chemoradiotherapy using intensity-modulated radiotherapy to deliver an escalated radiotherapy dose needs to be pursued to improve locoregional control.

Pattern of failure and long-term morbidity in patients undergoing postoperative radiotherapy for cervical cancer.

The objective of this study was to assess treatment outcomes in a large case series of cervical cancer patients undergoing postoperative radiotherapy in a single center. Case notes of women referred to the Christie Hospital during 1985-1997 for postoperative adjuvant radiotherapy for cervical cancer were reviewed. Of 478 women eligible for analysis, 282 (58.9%) underwent radical hysterectomy and 196 (41.1%) had nonradical hysterectomy. The disease-specific 5-year survival for the study population is 70.1%, with a 5-year risk of developing any recurrence of 30.5% and a 5-year grade 3 morbidity rate of 3.9%. Survival was significantly higher, ie, 80.9% vs 62.7% (P = 0.0001) and recurrence was significantly lower, ie, 18.6% vs 38.8% (P < 0.00005) in the group of women who had adjuvant radiotherapy following a nonradical hysterectomy compared with radical surgery. Thirty percent of women having "radical" surgery had positive resection margins and required postoperative adjuvant pelvic radiotherapy. Women with node-positive disease, who received adjuvant radiotherapy, had a high rate of distant metastases. These women would receive chemoradiotherapy now as primary treatment because of the risk of developing distant metastases. If, despite staging investigations, surgery reveals node-positive disease, then these women should receive adjuvant chemoradiotherapy. Survival was better in women who had nonradical surgery due to smaller volume disease when cancers were unsuspected and hence will have been cured by surgery alone. Multidisciplinary team working, as recommended by national guidelines from 1999, should allow better patient selection for treatment.

No relationship between thymidine phosphorylase (TP, PD-ECGF) expression and hypoxia in carcinoma of the cervix.

The expression of hypoxia-regulated genes promotes an aggressive tumour phenotype and is associated with an adverse cancer treatment outcome. Thymidine phosphorylase (TP) levels increase under hypoxia, but the protein has not been studied in association with hypoxia in human tumours. An investigation was made, therefore, of the relationship of tumour TP with hypoxia, the expression of other hypoxia-associated markers and clinical outcome. This retrospective study was carried out in patients with locally advanced cervical carcinoma who underwent radiotherapy. Protein expression was evaluated with immunohistochemistry. Hypoxia was measured using microelectrodes and the level of pimonidazole binding. There was no relationship of TP expression with tumour pO(2) (r=-0.091, P=0.59, n=87) or pimonidazole binding (r=0.13, P=0.45, n=38). There was no relationship between TP and HIF-1alpha, but there was a weak borderline significant relationship with HIF-2alpha expression. There were weak but significant correlations of TP with the expression of VEGF, CA IX and Glut-1. In 119 patients, the presence of TP expression predicted for disease-specific (P=0.032) and metastasis-free (P=0.050) survival. The results suggest that TP is not a surrogate marker of hypoxia, but is linked to the expression of hypoxia-associated genes and has weak prognostic power.

Expression of the proapoptotic protein Bid is an adverse prognostic factor for radiotherapy outcome in carcinoma of the cervix.

The Bcl-2 family of apoptotic regulators is thought to play an essential role in cancer development and influence the sensitivity of tumour cells to radiotherapy. Bid is an abundantly expressed Bcl-2 family protein playing a central role in various pathways of apoptosis by integrating and converging signals at the mitochondria. The relevance of apoptotic modulation by Bcl-2 and related proteins in tumour development and radiation response for human tumours remains undefined. Therefore, a study was made regarding the expression of Bid in patients with locally advanced cervix carcinoma who received radiotherapy. Bid expression was assessed using immunohistochemistry in pretreatment archival biopsies from 98 patients. The data were correlated with clinicopathologic characteristics and treatment outcome. Pretreatment tumour radiosensitivity data were available for 60 patients. Strong Bid expression was associated with a patient age less than the median of 52 years (P=0.034) and poor metastasis-free survival. In multivariate analysis, after allowing for stage, Bid expression was a significant prognostic factor for both disease-specific and metastasis-free survival (P=0.026). It is concluded that strong tumour Bid expression is associated with poor outcome following radiotherapy regardless of intrinsic tumour cell radiosensitivity, and is adverse prognostic for disease-specific and metastasis-free survival in younger patients.

Effect of forage quality on digestion and performance responses of cattle to supplementation with cooked molasses blocks.

We evaluated the effect of forage quality on response of cattle to supplementation with cooked molasses blocks. In Exp. 1, 175 heifers had ad libitum access to prairie hay (5.2% CP, DM basis). Treatments were a 2 x 3 factorial: supplementation with 0 or 1.96 kg/d of alfalfa DM, and supplementation with no cooked molasses block or with a low-protein or a high-protein cooked molasses block (14.4 and 27.5% CP, respectively, DM basis). There were no significant interactions between alfalfa and cooked molasses block for intake or gain. Forage intake and ADG were increased (P < 0.05) by alfalfa supplementation. Heifers fed high-protein cooked molasses blocks gained more (P < 0.05) weight than those fed low-protein cooked molasses blocks or no cooked molasses block. Heifers fed high-protein cooked molasses blocks ate more (P < 0.05) forage than those fed low-protein cooked molasses blocks, with heifers fed no cooked molasses block being intermediate. In Exp. 2, responses to cooked molasses blocks containing 33% CP (DM basis) were measured in 18 steers fed: 1) brome (8.4% CP), 2) alfalfa (19.2% CP), or 3) brome supplemented with 1.93 kg/d of alfalfa DM. Forages were available ad libitum. Forage DM intake was not affected by cooked molasses block and was greater (P < 0.05) for alfalfa than the alfalfa/brome mix, which in turn was greater (P < 0.05) than brome. Digestibility of DM was greater (P < 0.05) for alfalfa than brome or the alfalfa/brome mix and was not affected by cooked molasses block supplementation. Supplementation with cooked molasses blocks had only small effects on intake and digestion of medium- to high-quality forages, but it improved gains and feed efficiencies of heifers fed prairie hay ad libitum, with or without supplemental alfalfa.

Combinations of alfalfa hay and wet corn gluten feed in limit-fed growing diets for beef cattle.

Two experiments were conducted to evaluate the effects of alfalfa hay (AH) and wet corn gluten feed (WCGF) combinations on ADG and gain efficiency of cattle limit-fed growing diets. In Exp. 1, crossbred beef steers (n = 220; initial BW = 262 kg) were limit-fed diets consisting of steam-flaked corn and 40% WCGF (DM basis) with 0, 10, or 20% ground AH (0AH, 10AH, and 20AH, respectively). A fourth diet containing 20% ground AH and steam-flaked corn served as a control. All diets were fed once daily at 1.8% of BW (DM basis). Growing period ADG, gain efficiency, and dietary NE calculated from performance data decreased linearly (P < 0.01) with addition of AH to diets containing WCGF. Rate of DMI increased linearly (P < 0.05) with AH addition to diets containing WCGF. Following the growing period, steers were finished on a common diet offered ad libitum. Gain efficiencies during the finishing period were higher (P < 0.05) for steers fed the 20AH diet than for steers fed the control diet. In Exp. 2, crossbred beef heifers (n = 339; initial BW = 277 kg) were limit-fed diets containing steam-flaked corn with 10, 20, or 30% ground AH and 0, 40, or 68% WCGF in a 3 x 3 factorial arrangement, fed once daily at 1.6% of BW (DM basis). An AH x WCGF interaction occurred (P < 0.05) for growing period ADG and gain efficiency. Increasing AH or WCGF decreased cattle ADG, gain efficiency, and dietary NE with the exception of heifers fed 30AH/40WCGF, which had ADG that did not differ (P > 0.10) from that of heifers fed 20AH/0WCGF or 30AH/0WCGF, and which had greater gain efficiencies (P < 0.05) than heifers fed 30AH/0WCGF. Rate of DMI increased linearly (P < 0.01) with increasing AH and decreased linearly (P < 0.01) with increasing WCGF. Heifers were finished on diets containing 33% WCGF with 0 or 0.5% added urea (DM basis) offered ad libitum. Increasing WCGF in growing diets tended (linear, P < 0.10) to increase finishing ADG and gain efficiency, whereas increasing AH decreased (linear, P < 0.05) kidney, pelvic, and heart fat, and the percentage of carcasses grading USDA Prime. Urea tended to increase ADG (P < 0.10), but decreased (P < 0.04) the percentage of carcasses grading USDA Choice. Results suggest that the value of WCGF relative to steam-flaked corn in limit-fed growing diets might be improved in diets containing 30% AH relative to diets containing 10 or 20% AH.

A retrospective study of bladder morbidity in patients receiving intracavitary brachytherapy as all or part of their treatment for cervix cancer.

A retrospective study has been undertaken in an attempt to identify physical parameters that could confidently be used to predict an enhanced risk of bladder morbidity following intracavitary brachytherapy. 366 women received brachytherapy as all, or part, of their treatment for cervical cancer at the Christie Hospital in 1990 and 1991, and of these, 60 patients developed identifiable bladder morbidity (graded on a scale of 1-4 using the Franco-Italian glossary). These were age and stage matched with 60 asymptomatic women who were also treated for cervical cancer by brachytherapy during the same time period. The sizes of applicators used in the two groups were noted and compared. The two groups were also compared with respect to the heights of the applicator set above the symphysis pubis, the degree of anteversion or retroversion of the applicator sets and where possible, the doses at the International Commission on Radiation Units and Measurements (ICRU) bladder reference point. Where CT scans of the applications were available, these were reviewed to see if any differences in the size, shape or location of the bladder were apparent. No significant difference was found between the two groups of patients for any of the parameters investigated. The physical factors investigated in this study cannot be used to reliably predict bladder complications. There was a significant correlation between bladder morbidity and morbidity in other pelvic sites.

Supplemental betaine and peroxide-treated feather meal for finishing cattle.

These studies evaluated the effects of betaine, provided either as feed-grade betaine or as concentrated separator by-product (CSB; desugared beet molasses), on performance and carcass characteristics of finishing cattle. In Exp. 1, 175 steers (410 kg initial BW) were fed a finishing diet based on steam-flaked and dry-rolled corn, and treatments included 10.5 and 21 g/d feed-grade betaine and 250 and 500 g/d CSB (supplying 15.5 and 31 g/d of betaine, respectively). Steers fed feed-grade betaine had greater (linear and quadratic effects, P < 0.1) DMI than control steers, but ADG and gain efficiencies were not affected by treatment. Dressing percent and backfat thickness was greater (P < 0.1) for steers that received feed-grade betaine than for controls. Longissimus muscle area was lower (P < 0.1) for steers supplemented with either feed-grade betaine or CSB than for control steers. Yield grades were higher for cattle receiving feed-grade betaine (quadratic effect, P < 0.1) than for control steers. Marbling scores were not affected by supplemental betaine, but the percentage of carcasses grading USDA Select was lower (linear and quadratic effects, P < 0.1) for steers fed feed-grade betaine than for control steers, predominantly due to a greater percentage grading USDA Choice. In Exp. 2, 312 heifers (343 kg initial BW) were used in a finishing study to evaluate the effects of graded levels of feed-grade betaine and peroxide-treated feather meal on performance and carcass characteristics. Treatments included two finishing diets (containing peroxide-treated or untreated feather meal) and four levels (0, 4, 8, and 12 g/d) of feed-grade betaine arranged in a 2 x 4 factorial. No significant interactions occurred between treatment of feather meal and betaine. Treatment of feather meal with hydrogen peroxide (5% wt/wt) increased in situ protein degradability but did not alter DMI, ADG, gain efficiencies, or carcass characteristics of heifers when it replaced untreated feather meal in the diet. Top-dressing feed-grade betaine to the diets had no effect on DMI, ADG, and gain efficiencies. Marbling scores were greater (cubic effect, P < 0.05) for heifers fed diets top-dressed with 4 and 12 g/d of feed-grade betaine, but other carcass characteristics were not altered significantly. Overall, feed-grade betaine and CSB did not alter growth performance, but did have minor effects on carcass characteristics.

Lymphocyte radiosensitivity is a significant prognostic factor for morbidity in carcinoma of the cervix.

PURPOSE: To study the relationship between pretreatment peripheral blood lymphocyte radiosensitivity and morbidity following radiation therapy. METHODS AND MATERIALS: A prospective study was carried out in which patients with carcinoma of the cervix underwent radiation therapy. Intrinsic radiosensitivity was measured on pretreatment peripheral blood lymphocytes, using a limiting dilution clonogenic assay. Late morbidity was assessed using the Franco-Italian glossary. Results were correlated in an actuarial analysis. RESULTS: There were no correlations between the measured lymphocyte radiosensitivity (SF2) and colony-forming efficiency, patient age, tumor grade, or disease stage. For 83 patients, lymphocyte SF2 was a significant prognostic factor for the probability of developing both any (p = 0.002) and Grade 3 (p = 0.026) morbidity. In 174 patients, stage showed borderline significance as a prognostic factor for morbidity (p = 0.056). However, the type of treatment (intracavitary alone, intracavitary plus parametrial irradiation, single insertion plus whole-pelvis irradiation) was significantly associated with the probability of developing late complications (p = 0.013). There was a weak significant inverse correlation between lymphocyte SF2 and grade of morbidity (r = -0.34, p = 0.002). CONCLUSION: These data highlight the importance of normal cell radiosensitivity as a factor determining radiation therapy response. They also show that peripheral blood lymphocyte SF2 is a highly significant prognostic factor for the probability of developing late radiation morbidity, and that carcinoma of the cervix is a good model for testing radiobiologic principles in the clinic.

Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix.

There is increasing evidence that hypoxia-regulated gene expression influences tumor aggressiveness, contributing to the poorer outcome of patients with hypoxic tumors. The role of the transcriptional complex hypoxia-inducible factor-1 as an important mediator of hypoxia-regulated gene expression is one of the best documented pathways. Recently, it has emerged that certain tumor-associated carbonic anhydrases (CAs) can be added to the list of known hypoxia-inducible factor-responsive genes. Here we show that the immunohistochemical expression of the tumor-associated CA IX is correlated with the level of hypoxia in human cervical tumors. We performed a prospective study in 68 patients where needle electrodes were used to make direct measurements of tumor oxygenation levels. CA IX expression was evaluated immunohistochemically in pretreatment tumor biopsies. There was a significant positive correlation between the level of tumor hypoxia (HP5) and the extent of CA IX expression. A retrospective study of 130 squamous cell cervical carcinomas demonstrated that a semiquantitative immunohistochemical analysis of CA IX expression in tumor biopsies is a significant and independent prognostic indicator of overall survival and metastasis-free survival after radiation therapy. These studies provide clinical evidence that CA IX expression is up-regulated in hypoxic human cervical tumors and is associated with a poor prognosis. CA IX may act as an intrinsic marker of tumor hypoxia and poor outcome after radiation therapy. The level of CA IX expression may be used to aid in the selection of patients who would benefit most from hypoxia-modification therapies or bio-reductive drugs.

Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.

PURPOSE: To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF(2)) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. METHODS AND MATERIALS: Measurements of SF(2) and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp(alpha,rho)). Regression analysis was performed to assess the prognostic power of tcp(alpha,rho) vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF(2) and CFE measurements alone. RESULTS: In a univariate regression analysis of 44 patients, tcp(alpha,rho) was a better prognostic factor for both local control and survival (p < 0.001 and p = 0.049, respectively) than SF(2) alone (p = 0.009 for local control, p = 0.29 for survival) or CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp(alpha,rho) emerged as the most important prognostic factor for local control (p < 0.001, relative risk of 2.81). After allowing for tcp(alpha,rho), CFE was still a significant independent prognostic factor for local control, whereas SF(2) was not. The sensitivities of tcp(alpha,rho) and SF(2) as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. CONCLUSIONS: A Poisson tcp model incorporating individual SF(2), CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

Irradiation induced expression of CD31, ICAM-1 and VCAM-1 in human microvascular endothelial cells.

The adherence and migration of leukocytes through the endothelium of blood vessels is an important early event which occurs in normal tissues following ionizing irradiation but the underlying mechanisms are not fully understood. ICAM-1, VCAM-1 and CD31 are membrane proteins of endothelial cells, mediate this process when the vasculature is exposed to other inflammatory stimuli. In this study, expression of ICAM-1, VCAM-1 and CD31 on human dermal microvascular endothelial cells (HDMECs) at 72 hours post-irradiation using flow cytometry and northern analysis was determined. Dose-dependent increases in the surface expression and mRNA of ICAM-1 and CD31 were observed. In contrast VCAM-1 was practically undetectable on both control and irradiated HDMECs but was strongly expressed in TNF-alpha activated positive control HDMECs. The upregulation in ICAM-1 and CD31 was independent of radiation-induced changes in cell size, number and cell cycle stage. We suggest that ICAM-1 is active over a prolonged period whereas VCAM-1 acts only transiently in leukocyte-endothelial interactions in the irradiated microvasculature. The late upregulation of CD31 is a novel finding and may have a function in radiation-induced leukocyte extravasation, platelet adherence to the vascular wall and abnormal endothelial cell proliferation. Both ICAM-1 and CD31 seem to be therapeutic targets for the amelioration of radiation-induced normal tissue damage.

Pretreatment plasma TGF beta 1 levels are prognostic for survival but not morbidity following radiation therapy of carcinoma of the cervix.

PURPOSE: To determine whether pretreatment plasma-transforming growth factor beta 1 (TGF beta 1) levels are prognostic for tumor control and late morbidity following radiation therapy in carcinoma of the cervix. METHODS AND MATERIALS: The study was comprised of 79 patients undergoing radiotherapy with curative intent for Stage I-III carcinoma of the cervix. TGF beta 1 levels were analyzed using ELISA. Late morbidity was measured using the Franco-Italian glossary. Data were available for the pretreatment levels of circulating tumor markers that represent disease burden, and for peripheral blood lymphocyte radiosensitivity measured as SF2. RESULTS: Pretreatment TGF beta 1 levels were a significant prognostic factor for survival and local control. There were weak significant correlations of TGF beta 1 levels with disease stage and the levels of circulating tumor markers (CA125, TPA). There was a weak significant correlation between TGF beta 1 levels and normal cell radiosensitivity (lymphocyte SF2). There was no relationship between TGF beta 1 levels and grade of morbidity and pretreatment TGF beta 1 levels were not a significant prognostic factor for the probability of developing late morbidity. CONCLUSION: In carcinoma of the cervix, pretreatment TGF beta 1 levels reflect tumor burden and are a significant prognostic factor for survival. Despite an underlying weak relationship of TGF beta 1 levels with intrinsic normal cell radiosensitivity, pretreatment levels are not prognostic for the probability of developing late complications. This finding does not rule out the possible usefulness of measurements toward the end of treatment once tumor burden has been reduced.

Tumour oxygenation levels correlate with dynamic contrast-enhanced magnetic resonance imaging parameters in carcinoma of the cervix.

BACKGROUND AND PURPOSE: The Eppendorf pO(2) histograph is the 'gold standard' method for measuring tumour oxygenation. The method is not suitable for widespread application because its use is limited to accessible tumours. A non-invasive imaging technique would be an attractive alternative. Therefore, the relationships between tumour oxygenation and dynamic contrast-enhanced magnetic resonance imaging (MRI) parameters were investigated. MATERIALS AND METHODS: The study comprised 30 patients with carcinoma of the cervix. Tumour oxygenation was measured pre-treatment as median pO(2) and the proportion of values less than 5 mmHg (HP5) using a pO(2) histograph. Repeat measurements were obtained for nine patients following 40-45 Gy external beam radiotherapy giving a total of 39 measurements. Dynamic contrast-enhanced MRI using gadolinium was performed prior to obtaining the oxygenation data. Time/signal intensity curves were generated to obtain two standard parameters: maximum enhancement over baseline (SI-I) and the rate of enhancement (SI-I/s). RESULTS: Using the 39 measurements, there was a significant correlation between SI-I and both median pO(2) (r=0.59; P<0.001) and HP5 (r=-0. 49; P=0.002). There was a weak, borderline significant correlation between SI-I/s and both median pO(2) (r=0.29; P=0.071) and HP5 (r=-0. 34; P=0.037). There was a significant relationship between tumour size and SI-I (r=0.54; P<0.001), but not SI-I/s. In 29 tumours, where data were available, there was no relationship between histological assessment of tumour angiogenesis (intra-tumour microvessel density; IMD) and either MRI parameter. CONCLUSIONS: Tumour oxygenation levels measured using a pO(2) histograph correlate with dynamic contrast-enhanced MRI parameters. Therefore, non-invasive dynamic MRI may be a method for measuring hypoxia in human tumours.

Living kidney donation: recovery and return to activities of daily living.

To determine donor nephrectomy outcomes, a one page 20-item survey of 42 cases was reviewed, including demographics, intervals to normal activities (e.g., driving a car, returning to work), and an open inquiry about the donation process. Hospital records were also reviewed. Nephrectomy under general anesthesia was through an anterior flank, extra-retroperitoneal approach with postoperative epidural pain control. Early self-care, progressive ambulation, and prescriptive pulmonary care were undertaken to facilitate recovery. Length of stay averaged 3.4 (range 2-8) d, and mean hospitalization charge was $15 169 (range $10 733-S29 579). Thirty-four donors were employed outside the home; 18 (53%) returned to work within 4 wk, and the average duration away from work was 4.6 wk (range 6 d 10 wk). Within 2 wk, 25 (59%) were driving an automobile. Usual activities of daily living were fully performed by all donors at a mean of 4.8 wk (minimum 5 d). Forty respondents would donate again, and one might; one did not respond to this question. None reported intermediate or long-term disabilities and all reported return to their pre-donation level of activity. With the anterior extra-retroperitoneal nephrectomy, most donors were out of the hospital within 4 d, were driving within 2 wk, and returned to gainful employment within 4 wk. Living kidney donation, as viewed by the donors, was a positive experience, which appeared to disrupt their lives minimally.

A radiation-controlled molecular switch for use in gene therapy of cancer.

Ionising radiation induces the expression of a number of radiation-responsive genes and there is current interest in exploiting this to regulate the expression of exogenous therapeutic genes in gene therapy strategies for cancer. However, the radiation-responsive promoters used in these approaches are often associated with low and transient levels of therapeutic gene expression. We describe here a novel radiation-triggered molecular switching device based on promoter elements from the radiation-responsive Egr-1 gene and the cre-LoxP site-specific recombination system of the P1 bacteriophage. Using this system, a single, minimally toxic dose of radiation induced cre-mediated excision of a lox-P flanked stop cassette in a silenced expression vector and this resulted in amplified levels of CMV-promoter-driven expression of the exogenous tumour-sensitising gene, HSV-tk. This strategy could be used in combination with targeted delivery and tumour-specific promoters to elicit the tumour-targeted and prolonged expression of a variety of tumour-sensitising genes and provide an unprecedented level of control and tumour selectivity.

Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix.

The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy.