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C Glover

Publications and source records attributed to C Glover.

At least 19 recordsLinked to original sources
PubMed2002

Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer.

Cancer-related indoleamine (2,3)-dioxygenase up-regulation by interferon-gamma might influence quality of life by depleting serum tryptophan. We correlated serum tryptophan levels with immune activation and quality of life in patients with colorectal liver metastases. Venous blood was sampled from patients with primary colorectal cancer and from patients with metachronous colorectal liver metastases who completed quality of life and psychological questionnaires. Serum tryptophan, kynurenine, neopterin, interleukin 2 soluble receptor alpha (IL-2 sRalpha), soluble tumour necrosis factor receptor I (sTNF RI), interleukin 6, and C-reactive protein were measured. Liver metastasis volume was estimated by computerised tomography, and survival from blood sampling was noted. Sixty-six patients with colorectal cancer were studied (39 males; median age 66 years) of whom 25 had colorectal liver metastases only (17 males; median age 62 years; median liver metastasis volume 208 ml; median survival 234 days). Reduced serum tryptophan was significantly associated with Rotterdam Symptom Checklist physical symptom (r=-0.51, P=0.01) and Sickness Impact Profile (r=-0.42, P=0.04) scores, and correlated with increased serum neopterin (r=-0.36, P=0.003), IL-2 sRalpha (r=-0.51, P=0.01) and sTNF RI (r=-0.45, P=0.02) levels. Stepwise regression analyses suggested that serum tryptophan was an independent predictor of Rotterdam Symptom Checklist physical symptom (regression coefficient -20.78, P=0.01) and Sickness Impact Profile (regression coefficient -109.09, P=0.04) scores. The results supported a role for interferon-gamma-mediated serum tryptophan decrease in cancer-induced quality of life deterioration.

Adenocarcinoma↗
PubMed2002

Accuracy of investigations for asymptomatic colorectal liver metastases.

PURPOSE: The aim of this study was to prospectively assess the accuracy of the most promising imaging and tumor marker tests in liver metastasis diagnosis on follow-up of asymptomatic colorectal cancer patients during a median of 57 months after primary tumor resection. METHODS: One hundred patients, who were considered free of liver metastases after primary colorectal cancer resection and conventional follow-up, were screened for liver metastases by computerized tomography, magnetic resonance and ultrasound scans, ultrasound Doppler and isotope assessment of changes in hepatic arterial and portal venous flow, and serum estimation of carcinoembryonic antigen. Patients were followed up during a median of 41 months to identify those who developed liver metastases. RESULTS: The most sensitive technique was computerized tomography (sensitivity 0.67, specificity 0.91). Computerized tomography and magnetic resonance but not ultrasound were 100 percent accurate in differentiating liver metastases from other hepatic lesions. Techniques based on changes in hepatic arterial and portal venous flow had lower diagnostic accuracies (Doppler perfusion index, sensitivity 0.58, specificity 0.57; hepatic perfusion index, sensitivity 0.50, specificity 0.55), whereas ultrasound scanning identified only 43 percent (sensitivity 0.43, specificity 0.96) and serum carcinoembryonic antigen 33 percent (sensitivity 0.33, specificity 0.81) of patients with asymptomatic liver metastasis. Sensitivity could be improved by using tests in combination but this reduced specificity. CONCLUSIONS: Computerized tomography was the most sensitive test for asymptomatic colorectal liver metastases, but only 67 percent of affected patients were identified.

Aged↗
PubMed2002

Derivation of a toxicity-based model to predict how water chemistry influences silver toxicity to invertebrates.

The effect of altering water chemistry on acute silver toxicity to three invertebrate species, two Daphnids, Daphnia magna and Daphnia pulex, as well as an amphipod Gammarus pulex was assessed. In addition, the physiological basis of Ag(I) toxicity to G. pulex was examined. Daphnia magna and D. pulex were more sensitive than G. pulex and 48 h LC(50) values in synthetic ion poor water were 0.47, 0.65 and 2.1 microg Ag(I) l(-1), respectively. Increasing water [Cl(-)] reduced Ag(I) toxicity in all species, and increasing water [Ca(2+)] from 50 to 1,500 microM reduced Ag(I) toxicity in G. pulex. Whole body Na(+) content, but not K(+) or Ca(2+) was significantly reduced in G. pulex exposed to 6 microg Ag(I) l(-1) for 24 h, but there was no inhibition of whole body Na(+)/K(+)-ATPase activity. Both increasing water [Cl(-)] and [Ca(2+)] reduced this Ag(I)-induced Na(+) loss. For D. magna, the presence of 10 mg l(-1) humic acid or 0.5 microM 3-mercaptoproprionic acid (3-MPA) increased the 48 h LC(50) values by 5.9 and 58.5-fold, respectively, and for D. pulex the presence of 1 microM thiosulfate increased the 48 h LC(50) value by four-fold. The D. magna toxicity data generated from this study were used to derive a Daphnia biotic ligand model (BLM). Analysis of the measured LC(50) values vs. the predicted LC(50) values for toxicity data from the present and published results where water Cl(-), Ca(2+), Na(+) or humic acid were varied showed that 91% of the measured toxicity data fell within a factor of two of the predicted LC(50) values. However, the daphnid BLM could not accurately predict G. pulex toxicity. Additionally, the Daphnia BLM was under-protective in the presence of the organic thiols 3-MPA or thiosulphate and predicted an increase in the LC(50) value of 114- and 74-fold, respectively. The Daphnia toxicity based BLM derived from the present data set is successful in predicting Daphnia toxicity in laboratory data sets in the absence of sulfur containing compounds, but shows its limitations when applied to waters containing organic thiols or thiosulphate.

Amphipoda↗
PubMed2001

Continuous angiotensin II infusion increases tumour: normal blood flow ratio in colo-rectal liver metastases.

Insufficient blood flow within colo-rectal hepatic metastases is a factor which may limit drug delivery to, and thus the response of, these tumours to regional chemotherapy. Loco-regional flow may be manipulated pharmacologically to enhance the tumour blood flow relative to that of the normal liver. However, as yet, only transient effects have been studied. Patients receiving regional chemotherapy for unresectable hepatic disease were given a 45 min regional infusion of the vasoconstrictor Angiotensin II. Intrahepatic blood flow distribution was assessed serially by Positron Emission Tomography (PET) imaging together with the trapping tracer copper(II) pyruvaldehyde bis(N-4-methylthiosemicarbazone) (Cu-PTSM) labelled using copper-62. Eleven lesions in nine patients were studied, with no adverse effects. Prior to Angiotensin II administration tumour blood flow was generally found to be greater than that of liver (10/11 lesions; 8/9 patients; median TNR 1.3, iqr 0.9-2.5). A significant increase in relative flow to tumour was seen in response to 10 min Angiotensin II infusion in most cases (7/11 lesions; 7/9 patients; median TNR 2.1, iqr 1.4-4.1; P = 0.008), which appeared to be sustained throughout the 45 min infusion period (median TNR 1.85, iqr 1.3-3.8; P = 0.03). These effects were accompanied by transient elevation of mean arterial pressure, but no change in pulse rate. These observations suggest that prolonged regional vasoconstrictor administration could prove useful in the management of unresectable colo-rectal hepatic metastases, and that further development of vascular manipulation to enhance tumour targeting and drug delivery is warranted.

Angiotensin II↗
PubMed2001

Focal arterial transgene expression after local gene delivery.

BACKGROUND: Gene therapy for the treatment of vascular disease is limited by a low transfection efficiency and/or undesired biological responses. OBJECTIVE: To determine the transfection efficiency of delivering a liposome/DNA complex into balloon-injured rabbit arteries systematically or using a local delivery catheter. METHODS: The cationic liposomes N-[1-(2,3-dioleoyloxy) propyl]-N,N,N-trimethylammonium methyl-sulphate and dioleoyl-phosphatidylethanolamine were mixed 1:1 (wt/wt) and combined with the plasmid pCMV-AP containing the human placental alkaline phosphatase (AP) reporter gene. Before initiating the in vivo experiments, the optimal ratio of liposome to DNA complex and the persistence of transgene expression were determined in cultured vascular smooth muscle cells (SMC). In vivo, a Dispatch catheter was used for local delivery of the liposome/DNA complex into rabbit iliac arteries that had been balloon injured five days previously. The contralateral iliac or renal artery was also balloon injured, and liposomes with normal saline were delivered as a negative control. For the systemic delivery group, the liposome/DNA complex was delivered through an ear vein. RESULTS: AP expression in transfected SMC persisted for 28 days in vitro, although the percentage of transfected cells declined with time (eg, at 24 h it was 27.3%+/-2.9%, at 28 days it was 0.4%+/-0.1%). SMC proliferation in vitro enhanced the transfection efficiency 12-fold. In vivo, local delivery resulted in low levels of transfection in arteries harvested one day postdelivery; however, six of seven arteries harvested three days postdelivery had multiple regions of focal transgene expression involving all three arterial layers. For the systemic delivery group, two of nine arteries expressed the transgene. No transgene expression was found in uninjured arteries in either the local or systemic delivery groups. However, with both local and systemic delivery, balloon-injured arteries that received liposomes and saline showed low levels of AP expression in either the neointima, media or adventitia, presumably due to systemic recirculation of the liposome/AP construct. CONCLUSIONS: Liposome-mediated gene transfection can be successfully performed to all vessel layers in vivo by using a local delivery catheter, and may provide a therapeutic opportunity for modulating atherosclerosis and restenosis. Unwanted transfection at a distance may occur with catheter-based local delivery and requires further refinement.

Analysis of Variance↗
PubMed2001

Acute outcome with the flexicut directional coronary atherectomy catheter for the treatment of coronary in-stent restenosis.

In-stent restenosis (ISR) is a growing problem that is without a practical, efficacious treatment strategy. The purpose of this study was to determine the acute outcome of 17 patients with coronary ISR who were treated with the new 8 French (Fr), guide-catheter compatible Flexicut directional atherectomy catheter (Guidant Corporation, Santa Clara, California). Failure to deliver the device occurred in 2/17 ISR lesions. The remaining 15 ISR lesions were successfully debulked (e.g., minimum lumen diameter pre-procedure: 0.30 +/- 0.16 mm; post-atherectomy plus adjuvant therapy: 2.16 +/- 0.57 mm). Of note, the reference vessel diameter was only 2.62 +/- 0.63 mm. In 11/15 tissue specimens, macroscopic or microscopic particles consistent with stent material were found. There was an absence of acute closure or elevations of creatinine phosphokinase levels. Apart from 1 patient who developed recurrent restenosis, all other patients demonstrated either clinical improvement or lack of restenosis during early clinical follow-up (mean, 5 months). We conclude that use of the Flexicut catheter provides satisfactory debulking and early clinical outcomes in patients with ISR. Long-term follow-up of these and additional patients will be helpful in determining the efficacy of the Flexicut atherectomy catheter for the treatment of ISR.

Aged↗
PubMed2000

Venesection needle coring increases positive results with RT-PCR for detection of circulating cells expressing CEA mRNA.

We assessed whether circulating cell positivity using RT-PCR for carcinoembryonic antigen (CEA) cDNA was affected by venesection via a needle compared with a pre-aspirated venous cannula, and by increased PCR cycles. Systemic blood was sampled by needle and pre-aspirated cannula in 101 healthy individuals with no cancer history. After erythrocyte removal, samples were subjected to RT-PCR using specific primers for CEA, with 29 or 35 RT-PCR cycles. There was a significant difference between the number of subjects whose samples were negative when collected via needle venesection and positive when collected via pre-aspirated cannula, compared with positive by needle venesection and negative by pre-aspirated cannula for both 29 (P = 0.016) and 35 (P = 0.0111) RT-PCR cycles. Venesection technique (P = 0.01) and number of cycles (P = 0.003) were significant predictors of a positive result. Positive results in healthy subjects were reduced to less than 3% when an aspirated cannula was used for venesection and >29 PCR cycles were avoided.

Adult↗
PubMed2000

Correlation between tumour blood flow and fluorouracil distribution in a hypovascular liver metastasis model.

The poor response of colorectal liver metastases to fluorinated pyrimidine chemotherapy may be due to poor drug penetration into the tumour. Chemotherapy delivered by the blood to well perfused areas of tumour must reach less well perfused areas by diffusion. This study examined the relationship between intratumoural blood flow and drug uptake in a hypovascular liver metastasis animal model. We used a double isotope technique to examine the microdistribution of the blood flow tracer [125I]-iodoantipyrine (IAP) and fluorinated pyrimidine 5-[6-3H]-fluorouracil (5-FU) within intrahepatic, hypovascular HSN tumours. There was a significant fall (P < 10(-6)) in both IAP and 5-FU uptake between the liver/tumour edge and tumour centre which resulted in a significant covariation (P < 10(-5)) in tracer uptake with distance. The finding of a close covariation between blood flow and drug uptake in liver metastases suggested that 5-FU diffusion did not compensate for low 5-FU delivery in areas of poor tumour blood flow. The lower 5-FU levels in low compared with high areas of tumour blood flow could reduce the cytotoxic effect and increase the potential for development of drug resistance.

Animals↗
PubMed2000

Randomized trial of regional plus systemic fluorinated pyrimidine compared with systemic fluorinated pyrimidine in treatment of colorectal liver metastases.

AIM: We report a prospective randomized study comparing survival, response and toxicity in colorectal liver metastasis (CLM) patients treated by either hepatic arterial floxuridine (HAI) plus continuous systemic fluorouracil/folinic acid or systemic fluorouracil/folinic acid. METHODS: Eighty-four CLM patients received either HAI plus systemic fluorouracil/folinic acid or systemic fluorouracil/ folinic acid. RESULTS: Significantly more HAI plus systemic, compared with systemic only, patients developed WHO grade 3 or 4 diarrhoea (P=0.004), but significant quality of life differences were not detected. Liver metastasis partial response at 4 months after randomization was significantly greater (P=0.003) in HAI plus systemic (13/29, 45%) compared with systemic only (7/30, 23%) patients. There was no significant difference between groups in the proportion of patients who died from extrahepatic disease progression, or in survival. CONCLUSION: Combining regional with systemic fluorinated pyrimidines did not improve survival compared with systemic fluorinated pyrimidine.

Aged↗
PubMed2000

Pathophysiological insights from studies of retrieved coronary atherectomy tissue.

Coronary atherectomy offers the intuitive advantage of removing tissue mass in order to improve blood flow. A second major benefit of atherectomy is the opportunity to study lesion tissue and make pathophysiological insights. The value of the latter cannot be over emphasized, as current animal models for the study of atherosclerosis and restenosis are fraught with limitations. In this review, we outline some of the key descriptive findings that have emerged from the study of atherectomy specimens. Specifically, we will focus on the role of smooth muscle cell proliferation, thrombus organization and matrix formation in primary atherosclerotic lesions, as well as restenotic lesions after balloon angioplasty and stenting.

Apoptosis↗
PubMed2000

Demographic factors associated with knowledge of colorectal cancer symptoms in a UK population-based survey.

Greater public awareness of colorectal cancer symptoms might result in earlier presentation with improved cure by available treatments, but little is known about the extent of public knowledge of colorectal cancer symptoms. We asked a sample of the general population about knowledge of colorectal cancer symptoms and assessed demographic characteristics associated with differences in knowledge. A population-based telephone enquiry into knowledge of colorectal cancer-associated symptoms was conducted by a commercial telephone market-research company. Persons called were asked if they knew any symptom of colorectal cancer. Those who answered 'yes' were asked to state any symptom. The ability to state a colorectal cancer-associated symptom was correlated with demographic characteristics, and the strength of the relation between stating a colorectal cancer associated and unassociated symptom (discrimination) was also assessed. 1019 persons (respondents) from an age, sex, and social class-balanced general population sample were questioned. 328 (31%) of respondents stated a colorectal cancer-associated symptom. Regression analysis identified older age, female sex and higher social class as being significantly associated with ability to state a colorectal cancer-associated symptom. There was a weak trend (P = 0.054) towards a relationship between ability to state an associated symptom and stating fewer unassociated symptoms. These results reveal a total ignorance of colorectal cancer symptoms in the majority of respondents and suggest a need for improved public education about colorectal cancer. Public education should be directed at population groups with higher risk and the least knowledge of colorectal cancer.

Adolescent↗
PubMed1999

Contribution of diet, tumour volume and patient-related factors to weight loss in patients with colorectal liver metastases.

BACKGROUND: One of the difficulties in assessing the contribution of tumour-related factors to cancer cachexia is measurement of the extent of disease where dissemination to multiple organ sites has occurred. METHODS: In this study the extent of tumour (both tumour volume and increase in marker levels), diet and patient-related factors (appetite, metabolic hormones, immune activation, liver function and quality of life) were compared in patients with colorectal liver metastases who had lost at least 1 kg in body-weight (weight loss) and patients who had not lost 1 kg in body weight (stable weight) during the preceding month. RESULTS: Forty patients (22 men; 14 with weight loss) were studied. Liver metastasis volume was significantly greater in patients who lost weight than in those whose weight was stable (median (interquartile range) 1179 (245-1517) versus 119 (23-523) ml; P = 0.003). The prevalence of patients with raised levels of serum immune products was significantly greater in the weight loss group for soluble interleukin (IL) 2 receptor alpha (sIL2ralpha) (P = 0.03) and IL-6 (P = 0.05), but not for soluble tumour necrosis factor receptor 1 (sTNFr1) or neopterin. There were significant correlations between serum C-reactive protein and sIL2ralpha (rs = 0.68, P < 0.0001) and IL-6 (rs = 0.46, P = 0.008) but not sTNFr1 or neopterin levels. Significant differences in appetite, nausea, diet, energy intake, liver function tests and serum levels of metabolic hormones were not detected. CONCLUSION: Weight loss in patients with colorectal liver metastases was not explained by changes in diet, quality of life, or hormones, but activation of the innate and incomplete activation of the acquired immune systems may be involved. Agents that attenuate either the acute-phase inflammatory response or T lymphocyte IL-2 receptor upregulation might reduce weight loss in patients with metastatic disease.

Appetite↗
PubMed1999

Increased detection of circulating tumor cells in the blood of colorectal carcinoma patients using two reverse transcription-PCR assays and multiple blood samples.

The objectives of this study were to assess whether the use of two reverse transcription-PCR (RT-PCR) cDNA assays and multiple blood sampling increased circulating tumor cell detection in colorectal cancer patients. Systemic blood was sampled three times at 1-min intervals in 100 colorectal cancer patients (50 primary tumors only and 50 liver metastases), and in 70 control patients without known cancer. After removal of the erythrocytes, samples were subjected to separate RT-PCR reactions using specific primers for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20). Statistical analysis was performed by the two-sample binomial test and the one-sided McNemar test. There were significant increases in circulating tumor cell positivity when CEA and CK20 assays were used together as compared with either CEA or CK20 assay used alone. There were also significant increases in circulating tumor cell positivity for either CEA or CK20 assay used alone when the results from two blood samples were compared with the results from one sample. Circulating colorectal cancer cell positivity rose from 48% (CEA) and 34% (CK20) with one assay of one sample to 74% when both assays of three samples were used to identify circulating tumor cells. Three non-cancer control patients (4.3%) were positive for either CEA (two patients) or CK20 (one patient). Tumor cells were identified more frequently in the circulation of colorectal cancer patients than had been suggested previously. RT-PCR-based studies of the clinical significance of circulating cancer cells in colorectal cancer should involve multiple blood samples with identification of multiple tumor-related cDNA products.

Aged↗
PubMed1998

Relation between depression and circulating immune products in patients with advanced colorectal cancer.

We have previously suggested that colorectal liver metastases might produce 'toxins' that reduce both quality of life (QoL) and survival. In this study we assessed whether QoL in patients with such metastases was related to immune activation, as determined by increased serum levels of interleukin 6 (IL6), soluble tumour necrosis factor receptor 1 (sTNFr1), soluble interleukin 2 receptor alpha (sIL2r alpha) or the interferon-gamma marker neopterin. Serum IL6, sTNFr1, sIL2r alpha, neopterin, alkaline phosphatase and carcinoembryonic antigen levels, liver metastasis volume, and QoL (Hospital Anxiety and Depression [HAD] scale, Rotterdam Symptom Checklist [RSC], and Sickness Impact Profile [SIP]) were measured in 43 patients. There were significant positive correlations between serum sIL2r alpha and HAD depression score (r = 0.66, P = 0.0001), RSC physical symptom score (r = 0.46, P < 0.01), and SIP score (r = 0.47, P = 0.009). Multiple regression analysis suggested that serum sIL2r alpha level was a significant independent predictor of HAD depression score. Although survival was shorter (logrank test P < 0.05) where sIL2r alpha, sTNFr1 and IL6 levels were higher, the ability of sIL2r alpha to predict HAD depression score was independent of survival.

Aged↗
PubMed1997

Effect of regional and systemic fluorinated pyrimidine chemotherapy on quality of life in colorectal liver metastasis patients.

PURPOSE: Since systemic and regional (HAI) fluorinated pyrimidine chemotherapies offer similar survival benefit in treatment of colorectal liver metastases (CLM), we sought to identify their impact on quality of life (QoL), which might be a useful indicator of treatment preference. METHODS: We compared QoL in 135 CLM patients managed by symptom control (n = 49 patients), systemic fluorouracil (5FU)/folinic acid (n = 35), or hepatic arterial floxuridine (FUDR) (n = 51). Full blood count and liver function tests, World Health Organization (WHO) toxicity criteria, and QoL (Rotterdam Symptom Checklist [RSC], the Sickness Impact Profile [SIP], and the Hospital Anxiety and Depression scale [HAD]) were measured monthly in all patients. RESULTS: The HAD anxiety score was significantly increased in symptom control compared with chemotherapy patients 1 month after randomization. There was a significant increase in RSC physical score (repeated measures, P = .05), and in scores for sore mouth (P < .01), dry mouth (P < .01), and tingling hands and feet (P < .01) in systemic chemotherapy compared with symptom control patients. Significant QoL differences (repeated measures and Mann-Whitney U [MWU]) between HAI and symptom control patients were not detected. Systemic chemotherapy patients lived for significantly longer (log-rank test, P < or = .0001) with abnormal HAD anxiety, RSC psychosocial, or RSC sore mouth scores compared with HAI patients, but there were no overall survival differences. CONCLUSION: Randomization to symptom control only was associated with increased anxiety. QoL with systemic chemotherapy was impaired by side effects. HAI was associated with similar survival to systemic chemotherapy but with better sustained QoL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Analysis of meningococcal serogroup C-specific antibody levels in British Columbian children and adolescents.

The effects of age, sex, and possible prior exposure to serogroup C meningococci on group C-specific antibody levels (total and functional) were examined in 2- to 19-year-olds just before and 1 and 12 months after immunization with divalent (groups A + C) meningococcal capsular polysaccharide vaccine. Only age was found to have a significant effect on antibody levels. At 1 month, only 50% of 2- to 6-year-olds had detectable serum bactericidal antibody, in contrast to 84.1% and 96.3% of 9- to 12- and 13- to 19-year-olds respectively. By 12 months, only 20%, 40.9%, and 53.8% of subjects in these age groups had serum bactericidal antibody, suggesting that current meningococcal C polysaccharide vaccines provide only short-term protection. However, the drop in total specific antibody levels (by EIA) was less pronounced. Persistence of antibodies detectable by EIA (but not serum bactericidal antibodies) suggests that this vaccine may also give rise to antibodies of low affinity or directed to nonfunctional (nonprotective) epitopes (or both).

Adolescent↗
PubMed1996

Relation between tumor size, quality of life, and survival in patients with colorectal liver metastases.

PURPOSE AND METHODS: This study assessed the relationship between survival, tumor size, and quality of life (QoL; Rotterdam Symptom Checklist [RSC], Hospital Anxiety and Depression Scale [HAD], and Sickness Impact Profile [SIP]) in 50 patients with colorectal liver metastases (CLM). RESULTS: Physical symptom score (RSC) was a stronger survival predictor than tumor size measured on computed tomographic (CT) scan. The best model for predicting survival included QoL questions about diarrhea, eating, restlessness, and ability to work and sleep. The only clinically measured variable included in this best survival prediction model was serum alkaline phosphatase level. This is the first study to show that QoL indices predict survival in CLM. The findings suggest that differences in tumor products and not just in tumor size could influence patient fitness and survival in CLM. Such differences are more accurately estimated by QoL assessment than measurement of tumor size. CONCLUSION: QoL provides a better survival estimate than measurement of tumor size and could be used as a surrogate end point for survival in treatment trials.

Aged↗