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L Campion

Publications and source records attributed to L Campion.

15 recordsLinked to original sources
PubMed2001

Genetic polymorphism at the glutathione S-transferase (GST) P1 locus is a breast cancer risk modifier.

The isolation of full-length cDNAs of naturally occurring GSTP1 gene variants, and the demonstration that these alleles are distributed in the normal population, have provided conclusive evidence that the human GSTP1 gene locus is polymorphic and that specific GSTP1 alleles may be associated with different risk for cancers or other diseases. Recent data have indicated that the different GSTP1 alleles encode proteins with different enzymatic activities against carcinogens. In this case-control study, we examined the effect of the GSTP1 genetic polymorphism and its interaction with other factors to determine breast cancer risk. GSTP1 and GSTM1 genotypes of 220 breast cancer patients and 196 controls, all residents of western France, were examined. Data on menopausal status and family cancer history were obtained from 195 patients and 147 controls. Exons 5 and 6 of the GSTP1 gene, which contain the polymorphic nucleotide transitions, were analyzed by DNA polymerase chain reaction-restriction fragment length polymorphism to distinguish between the GSTP1 alleles. In the control population, GSTP1 allelic frequencies were 64.3%, 26.0% and 9.7%, respectively, for GSTP1*A, GSTP1*B and GSTP1*C. In the breast cancer patients, the frequencies were 67.9% for GSTP1*A, 26.8% for GSTP1*B and 5.3% for GSTP1*C. In multivariate analysis, breast cancer risk increased by 7.7-fold (p < 0.001) in women with a family history of cancers and 2.18-fold (p = 0.026) in non-GSTP1*C individuals. GSTM1 genotypes did not emerge as risk factor. Our results show that in addition to well-known risk factors, in particular, a family history of cancer, GSTP1 allelopolymorphism is a significant modifier of breast cancer risk. The results also suggest a protective role against breast cancer for the GSTP1*C allele.

Adult↗
PubMed2001

Long-term complications of total body irradiation in adults.

PURPOSE: To report long-term pulmonary, thyroid, and ocular complications in patients who had conditioning regimens including total body irradiation (TBI) before bone marrow transplantation (BMT). METHODS AND MATERIALS: Between June 1986 and December 1995, 478 patients received TBI in our institution. The present study includes 186 adult patients who had complete remission lasting one year or more after BMT. There were 108 males and 78 females. Median age was 36.5 years (range 15-60). Initial diagnoses were lymphomas (50%), acute lymphoid leukemias (16%), acute myeloid leukemias (16%), chronic myeloid leukemia (13%), aplastic anemia (3%), and myelodysplasia (2%). At the time of BMT, 43.5% of patients were in complete response and 56.5% in partial response. Treatment consisted of a single dose TBI at 10 Gy in 9% and fractionated TBI delivering 12 to 13.5 Gy in 6 fractions in 91%. From 1986 to October 1991, TBI was performed in lateral position with 9 MV energy (57% of patients) and thereafter in alternate prone and supine positions with 15 MV energy (43%). Chemical conditioning regimen was cyclophosphamide (60 mg/kg at D-4 and D-3) in 69% and CBV (cyclophosphamide 1500 mg/m(2) from D-6 to D-3, BCNU 300 mg/m(2) at D-6, VP-16 200 mg/m(2) from D-6 to D-4) in 25%. Fifty eight percent of patients received autologous and 42% allogeneic BMT. All patients had clinical, biologic, and functional examinations at one-year intervals. RESULTS: Median follow-up from BMT was 49 months (range 12-136). Late pulmonary effects were observed only in functional explorations, without clinical effect, including restrictive syndrome in 8% and alteration in the diffusing capacity of carbon monoxide in 12%. No patient showed clinical thyroid symptoms, and 10% developed biologic dysfunction: hypothyroidism (6.5%), thyroiditis (3%), and Basedow disease (0.5%). Ocular complications occurred in 29.5%, including cataract (15%), dry syndrome (13%), and keratitis (1.5%). In univariate and multivariate analysis, pulmonary complications were statistically increased by chronicle graft vs. host disease (GVHD) vs. no (p = 0.02), prone and supine vs. lateral TBI position (p = 0.02), and with 15 MV vs. 9 MV beam energy (p = 0.02). Cataract occurred less frequently with fractionated than with single-dose TBI (p = 0.000002). No differences were observed regarding age, sex, initial diagnosis, status at the time of BMT, conditioning chemotherapy regimen, and total dose of TBI. CONCLUSION: From this retrospective study it was shown that long-term complications of TBI were not symptomatic in most patients. The role of parameters of irradiation and especially position of treatment and beam energy should be emphasized and assessed with a longer follow-up.

Adolescent↗
PubMed2000

Salvage extended-field irradiation in follicular non-Hodgkin's lymphoma after failure of chemotherapy.

PURPOSE: To evaluate the efficacy of total abdominopelvic (TAI) and total body irradiation (TBI) in heavily pretreated follicular non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: From 1983 to 1998, 34 patients received TAI (n = 22) or TBI (n = 12). All had Stage III or IV, Class B, C, D NHL in the working formulation and failed after receiving 1-5 regimens of chemotherapy. TAI was given at 20 Gy over a 3-week period. TBI was delivered in two successive half-body irradiations of 15 Gy over a 2-week period with a 4-week interval between each. RESULTS: Mean follow-up from TAI or TBI was 120 months (range, 6-180). Seventy-six percent of patients achieved complete response and 24% partial response. Median survival was 62 months, 5-year and 10-year overall survival was 59% and 41%, and disease-free survival was 56% and 30%, respectively. Grade III or IV toxicity was gastrointestinal in 38% of patients and hematologic in 30%. No toxic death or delayed complications were observed. CONCLUSION: Extended-field irradiation is feasible and efficient after failure of chemotherapy in follicular NHL.

Adult↗
PubMed2000

Treatment of bone metastases of prostate cancer with strontium-89 chloride: efficacy in relation to the degree of bone involvement.

This retrospective study evaluated the toxicity and efficacy of strontium-89 chloride (Metastron, Amersham) in 94 patients with painful bone metastases of prostate cancer (117 injections of 150 MBq) and compared the efficacy of treatment in patients with moderate and extensive bone involvement. The predictive value of flare response with regard to analgesic response was also studied. High-grade leukothrombopenias were observed after only 5% of injections. An improvement in quality of life was obtained in 65% of cases, a decrease in pain in 78% (31% complete response) and a reduction of analgesics in 60%. Efficacy was significantly better for pain decrease (P=0.005) and reduction of analgesics (P=0.018), and response was significantly longer (P<0.0035) in patients with moderate than in patients with extensive bone involvement. The flare response observed in 23% of cases was not predictive of pain response (P=0.919) or reduction of analgesics (P=0.353). A second dose prolonged analgesia in three-quarters of cases without any apparent increase in toxicity. These results confirm the benefit of 89Sr chloride for the treatment of metastatic bone pain and suggest that internal radiotherapy should be started earlier. A bone scan could be proposed at the time of hormonal escape resulting in bone pain, and internal radiotherapy could be initiated when several metastatic foci exist, even if only one is painful. In this way, pain-free follow-up could be prolonged, and the transition to other therapeutic approaches, particularly opioids, delayed.

Aged↗
PubMed1999

Antithyroid drugs and Graves' disease--prospective randomized assessment of long-term treatment.

OBJECTIVE: Although antithyroid drugs (ATD) are widely used in the treatment of Graves' disease, management protocols, especially treatment duration, remain a subject of debate. The rate of relapse after short-term regimens of less than 6 months with ATD at decreasing doses is higher than after longer treatments from 12 to 24 months. As no prospective study has provided data on even longer protocols exceeding 2 years, we conducted a prospective trial to determine potential benefits of a 42-month treatment compared with an 18-month treatment. DESIGN, PATIENTS AND MEASUREMENTS: The aim of this prospective randomized trial was to compare relapse rates achieved two years after treatment withdrawal in patients who received carbimazole at decreasing doses for 18 months (n = 62) vs 42 months (n = 72). In addition to clinical relapse rate, the percentage of patients who normalized antithyroperoxidase (TPO) antibody and anti-TSH receptor stimulating antibody (TSAb) levels and early iodine uptake at the end of treatment were assessed as outcome criteria. RESULTS: The relapse rate two years after discontinuation of treatment did not differ significantly in patients treated for 18 months from those treated for 42 months (36% vs 29%, NS). At the end of treatment, there was no significant difference between the two groups in the percentage of anti-TPO positive patients (53% vs 46%, NS) or early iodine uptake (27% vs 21%, NS). Although the percentage of patients with TSAb was significantly lower in the 42-month treatment group (18% vs 42%, P = 0.004) at treatment withdrawal, the percentage of TSAb-positive patients did not significantly decrease between 18 and 42 months in this group (27% vs 18%, NS). CONCLUSION: Treatment duration greater than 18 months did not improve remission rate determined 2 years after treatment withdrawal or immunological variables or early iodine uptake measured at the time of discontinuation of treatment. These findings would indicate that, when a defined duration treatment is planned, prolonging treatment beyond 18 months does not provide any additional benefit.

Adolescent↗
PubMed1999

Toxicity and efficacy of radioimmunotherapy in carcinoembryonic antigen-producing medullary thyroid cancer xenograft: comparison of iodine 131-labeled F(ab')2 and pretargeted bivalent hapten and evaluation of repeated injections.

This study compared the toxicity and efficacy of 131I-labeled bivalent hapten pretargeted by anti-carcinoembryonic antigen (CEA)/anti-N alpha-(diethylenetriamine-N,N,N',N''-tetraacetic acid-indium(F6-734) bispecific antibody [affinity enhancement system (AES) reagents] with 131I-labeled anti-CEA F(ab')2 (131I-F6) in mice grafted with a human medullary thyroid carcinoma. Repeated injections of AES reagents were also evaluated. Mice bearing TT tumor xenografts were treated with 37, 74, or 92.5 MBq of AES reagents, two injections of 74 MBq of AES reagents 45 days apart, or 37 or 92.5 MBq of 131I-F6. Control groups were treated with nonspecific 131I-labeled F(ab')2, nonspecific AES reagents, nonradiolabeled F6, F6-734 bispecific antibody, and nonradiolabeled bivalent hapten or received no injection. For AES treatments, bispecific antibody was injected 48 h before the hapten. Animal weight, hematological toxicity, tumor volume, and serum thyrocalcitonin were monitored during 5 months. At 92.5 MBq, weight loss was significantly lower after AES than F6 treatment (P = 0.004). The percentages of leukocyte count changes were significantly lower after AES than F6 at 37 and 92.5 MBq (P = 0.01 and 0.04, respectively). The percentage of platelet count changes was significantly lower with AES at the 92.5-MBq dose level (P = 0.04). In the group injected twice with AES reagents, toxicity was not significantly increased after the second treatment. Tumor response was observed in all cases but was significantly longer with repeated treatments of 74 MBq AES reagents than with a single treatment (P = 0.004). Two complete responses were observed with repeated treatments. Changes in thyrocacitonin level paralleled those in tumor volume. These results indicate that pretargeted radioimmunotherapy was at least as efficient as one-step radioimmunotherapy and markedly less toxic. Repeated treatments with AES reagents increased efficacy without increasing toxicity.

Animals↗
PubMed1999

Bispecific antibody and bivalent hapten radioimmunotherapy in CEA-producing medullary thyroid cancer xenograft.

UNLABELLED: The purpose of this study was to compare the toxicity and efficacy of two-step radioimmunotherapy using a bispecific anticarcinoembryonic antigen (CEA)/anti-diethylenetriamine pentaacetic acid (DTPA) antibody (F6-734 bispecific monoclonal antibodies (BsMAbs) and an 131I-di-DTPA-TL bivalent hapten with F(ab')2 fragments of the same directly labeled anti-CEA 131-F6. METHODS: Eight groups of nude mice subcutaneously grafted with the human TT medullary thyroid cancer cell line were injected once tumor volume reached about 200 mm3. Two groups received 37 or 92.5 MBq (1 or 2 nmol) 131I-di-DTPA-TL 48 h after injection of 2 or 4 nmol F6-734 BsMAb and two groups received 37 or 92.5 MBq (250 microg) 131I-F6. Four control groups were treated respectively with (a) 92.5 MBq nonspecific 131I-734 fragments, (b) 92.5 MBq 131I-di-DTPA-TL 48 h after injection of a mixture of irrelevant F6-679 (anti-CEA/anti-histamine) and G7A5-734 (anti-melanoma/anti-DTPA) BsMAb, (c) 250 microg nonradiolabeled F6, and 250 microg F6-734 BsMAb and then 48 h later 1.25 nmol of nonradiolabeled hapten. A control group received no injections. Toxicity was evaluated by determining animal weight and the number of leukocytes and platelets, and efficacy by variation in tumor volume and thyrocalcitonin during a 90-d period. Histological analysis of tumors and statistical studies were performed. RESULTS: The time required for the tumor to double in size was respectively 57 and 86 d with 37 and 92.5 MBq F6-734/131I-di-DTPA-TL and 44 and 65 d with 37 and 92.5 MBq 131I-F6. Changes in thyrocalcitonin levels were parallel to those in tumor volume. Weight loss was 5%, leukocyte nadirs respectively 1640+/-838 and 1560+/-1160/mm3 and platelet nadirs 1.46+/-0.52 10(6)/mm3 and 0.73+/-0.38 10(6)/mm3 after injections of 37 and 92.5 MBq F6-734/1311-di-DTPA-TL. Weight loss was respectively 8% and 16%, leukocyte nadirs 50+/-100/mm3 and 175+/-50/mm3 and platelet nadirs 0.71+/-0.18 10(6)/mm3 and 0.48+/-0.11 10(6)/mm3 after injections of 37 and 92.5 MBq 131I-F6. CONCLUSION: Two-step radioimmunotherapy was as efficient as the one-step system and markedly less toxic.

Animals↗
PubMed1998

Clinical and statistical evaluation of self-monitoring blood glucose meters.

OBJECTIVE: Our objective was to compare statistical and clinical methods for the evaluation of five self-monitoring blood glucose (SMBG) meters. RESEARCH DESIGN AND METHODS: Two successive capillary blood glucose measurements were performed, and a simultaneous laboratory venous glucose measurement was used as the reference value. Accuracy was studied by comparing each of the two successive meter values with the reference value by 1) a Spearman's correlation test, 2) a Wilcoxon's paired test, 3) the percentage of values within the 10% interval of the reference value according to the American Diabetes Association consensus statement, and 4) the error grid analysis. RESULTS: The first two methods did not discriminate between the SMBG systems: r was >0.92 for the five meters, and a significant difference between the meter and reference values was found for all but one meter. The two other methods allowed classification of the devices into three groups according to their accuracy: good (two meters), acceptable (two meters), and unacceptable (one meter). These two methods gave consistent results and both had a good reproducibility, because the classification was similar for the two successive measurements. CONCLUSIONS: Both the Spearman's and Wilcoxon's paired tests, although commonly used, are inappropriate to evaluate SMBG systems. The percentage of SMBG values within the +/-10% interval and the error grid analysis are more accurate, because they consistently classified the five glucose meters tested in our study with a high degree of reproducibility.

Adult↗
PubMed1998

Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas.

A significant link between 5-fluorouracil (5FU) plasma concentration and its therapeutic activity has been demonstrated in colon and head and neck cancer patients for 5FU used as a continuous infusion. Dose adjustment based on pharmacokinetic follow-up has been proposed to decrease hematological and digestive toxicities, but the clinical impact of this approach has not yet been demonstrated. A randomized multicentric study was conducted to evaluate the clinical interest of 5FU dose adaptation guided by pharmacokinetics. One hundred twenty-two head and neck cancer patients were randomly assigned to receive induction chemotherapy with cisplatin (100 mg/m2, day 1) and 5FU (96-h continuous infusion), either at standard dose (St-arm; 4 g/m2) or at a dose adjusted according to the 5FU area under the curve (AUC0-48h; PK-arm). In total, 106 patients were evaluable for toxicity and response. In the PK-arm (n = 49), 5FU doses and area under the curve were significantly reduced during cycle 2 and cycle 3 (P < 0.001) as compared with the St-arm (n = 57). Grade 3-4 neutropenia and thrombopenia were significantly more frequent in the St-arm as compared with the PK-arm (17.5% versus 7.6%, respectively; P = 0.013). No grade 3-4 mucositis occurred in the PK-arm, whereas 5.1% was observed in the St-arm (P < 0.01). The objective response rate was comparable in the two treatment arms: 77.2% in the St-arm versus 81.7% in the PK-arm. The present study is the first to demonstrate, in a randomized design, the clinical interest of an individual 5FU dose adaptation based on pharmacokinetic survey, in terms of therapeutic index improvement.

Adult↗
PubMed1994

[Susceptibility of LDL to lipid peroxidation in non-insulin-dependent diabetes mellitus with or without macroangiopathy].

Since oxidized LDL may play a role in the genesis of atheroma, which is the primary complication of non-insulin-dependent diabetes mellitus (NIDDM), we investigated whether the LDL of diabetic patients were more prone to oxidation than those of healthy controls. We therefore studied the susceptibility of LDL to oxidation by phenylhydrazine (LDL-PO) in NIDDM patients with or without macroangiopathy, and in controls. Results showed that the LDL of patients with macroangiopathy (n = 50) were more susceptible to oxidation than those of both NIDDM patients without vascular complications (n = 50) and controls (n = 50). In diabetic patients, there was a positive correlation between LDL-PO and the following parameters: total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B. In contrast, there was no correlation between LDL-PO and the parameters of glycemic control (fasting glucose, HbAlc). After analyzing the composition of LDL, it appeared that LDL-PO values in diabetic patients were positively correlated with those of all LDL constituents. The increase in LDL-PO observed in the group of NIDDM patients with macroangiopathy could be a consequence of an increase in the LDL triglyceride content in these patients.

Apolipoproteins B↗
PubMedDate not supplied

Increase in thiobarbituric acid-reactive substances and vascular complications in type 2 diabetes mellitus.

Lipid peroxidation was assessed by measuring the concentrations of thiobarbituric acid-reactive substances in plasma from 204 Type 2 diabetic patients, relative to 107 controls. The concentrations obtained in diabetic patients (3.08 +/- 0.37 mumol/l) were significantly higher than in controls (2.80 +/- 0.34 mumol/l) (p < 0.0001). Values were also significantly increased in patients with macroangiopathy and/or microangiopathy (3.17 +/- 0.41 mumol/l), relative to patients void of vascular complications (2.92 +/- 0.34 mumol/l) (p < 0.001). Elevated concentrations were independent of the type of vascular complication and their possible associations. In patients without vascular affection, thiobarbituric acid-reactive substances were in significantly higher concentrations in hypertensive (3.07 +/- 0.36 mumol/l) than in normotensive (2.87 +/- 0.29 mumol/l) (p < 0.01) patients. There was a correlation between these values and those of total cholesterol (r = 0.46, p < 0.0001) and triglyceride (r = 0.45, p < 0.0001). Statistical analysis by multivariate logistical regression revealed that among the independent factors (TBARS, APO A1, hypertension, age), thiobarbituric acid-reactive substances constituted the parameter most strongly linked to the existence of vascular complications. This study has evidenced a lipid peroxidation disorder in non insulin- dependent diabetes mellitus, more marked in patients with vascular affection. Thiobarbituric acid-reactive substances appear to be an independent marker of vascular complications in Type 2 diabetes.

Adult↗