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C Lejeune

Publications and source records attributed to C Lejeune.

At least 19 recordsLinked to original sources
PubMed2002

Bayesian population model of methotrexate to guide dosage adjustments for folate rescue in patients with breast cancer.

BACKGROUND: Methotrexate (MTX) infusions may induce severe side-effects, and alkaline hydration along with folinic acid rescue is a common way to reduce such toxic risks. The purpose of this study was to develop an adaptive rescue strategy based upon the early detection of patients with impaired MTX elimination. METHODS AND RESULTS: In this study, we propose a simple population-based Bayesian approach for predicting MTX plasma concentration from a limited number of samples, so as to adapt both duration and dosage of the rescue agent to be used next. Ten kinetic profiles obtained after 10 courses of MTX (1.5 g/m2) in seven patients with inflammatory breast cancer were used to establish the population pharmacokinetic parameters (Cl, 8.16 L/h; t1/2, 12.7 h). This population was next involved in the Bayesian estimation of MTX individual pharmacokinetic parameters from only two blood samples (T24 and T36 h), thus allowing one to forecast the elimination of this drug by predicting MTX levels at 48 h. According to the MTX concentrations predicted during the elimination phase, folinic acid rescue was then prolonged in patients likely to be overexposed. CONCLUSION: The Bayesian estimation presented in this study was an easy and convenient method to efficiently detect patients with impaired MTX elimination in routine clinical practice. This information enabled the introduction of strategies for minimizing the risk of severe drug toxicity.

Adult↗
PubMed2001

Estimation of screening test (Hemoccult) sensitivity in colorectal cancer mass screening.

3 controlled cohorts of mass-screening for colorectal cancer using a biennial faecal occult blood (HemoccultII test on well-defined European populations have demonstrated a 14% to 18% reduction in specific mortality. We aimed to estimate the sensitivity (S) of this HemoccultII test and and also mean sojourn time (MST) from French colorectal mass-screening programme data. 6 biennial screening rounds were performed from 1988 to 1998 in 45 603 individuals aged 45-74 years in Saône-et-Loire (Burgundy, France). The prevalent/incidence ratio was calculated in order to obtain a direct estimate of the product S.MST. The analysis of the proportional incidence and its modelling was used to derive an indirect estimate of S and MST. The product S.MST was higher for males than females and higher for left colon than either the right colon or rectum. The analysis of the proportional incidence confirmed the result for subsites but no other significant differences were found. The sensitivity was estimated at 0.57 and the MST at 2.56 years. This study confirms that the sensitivity of the Hemoccult test is relatively low and that the relatively short sojourn time is in favour of annual screening.

Aged↗
PubMed2001

Contribution of a pacemaker bradycardia detection algorithm in the study of patients with carotid sinus syndrome.

While carotid sinus syndrome (CSS) is often suspected as a cause of syncope in the elderly, whether it represents an indication for cardiac pacing may remain uncertain. Bradycardia algorithms included in pacemakers are now able to establish a precise relationship between spontaneous asystole and occurrence of symptoms and strengthen the indication for permanent pacing. This study included seven men and three women (70.5 +/- 7.3 years of age) who, over an average period of 54.1 +/- 17 months, had suffered from syncope (12.6 episodes/patient) and presyncope (11.2 episodes/patient) attributed to pure cardioinhibition (2 patients) or mixed CSS (8 patients). Other sources of symptoms were excluded by thorough clinical evaluations, including Holter monitoring, echocardiography, and electrophysiological testing. All patients received a CHORUS 6234 pacemaker, the memory of which includes a dedicated bradycardia detection algorithm capable of storing atrial and ventricular chains, and date and time of the last ten pauses and/or bradycardic events. After a initial period of 14.7 +/- 8 months, during which symptoms were suppressed, the bradycardia algorithm was activated. From then on, a cumulative increase in the number of patients presenting with diurnal pauses was measured (1 month, n = 0; 3 months, n = 6; 9 months, n = 7; 2 years, n = 8). Fourteen episodes of diurnal asystole were recorded. The mean duration of the longest episodes of spontaneous ventricular standstill was 6,319 +/- 1,615 ms and was due to sinoatrial block (n = 7), atrioventricular block (n = 5), and a combination of both (n = 2). In conclusion, activation of the CHORUS bradycardia algorithm allowed confirmation of the appropriateness of permanent pacing in a majority of patients suffering from CSS.

Aged↗
PubMed2001

[Withdrawal syndromes of newborns of pregnant drug abusers maintained under methadone or high-dose buprenorphine: 246 cases].

UNLABELLED: Perinatal prognosis of pregnant drug abusers is better with intensive prenatal care and substitution maintenance programs. There is a large body of data in the literature on methadone (MTD), but very little on high-dose buprenorphine (HDB). The objective of this study was to compare 2 groups of pregnant women maintained on MTD or HDB for perinatal events. STUDY DESIGN: Prospective multicentric study; all neonates (NN) whose mothers has been maintained during pregnancy on MTD or HDB were included by 34 French perinatal centers with specialized staff for care of these pregnant drug abusers. RESULTS: Two hundred and forty-six pregnant women were included: 93 (38%) MTD and 153 (62%) HDB. Social and perinatal data, prenatal care and factors correlated with poor prenatal care are reported. Forty-six percent of the pregnant women had good prenatal care; 88% had peridural analgesia; mean birthweight=2838g; mean gestational age=38.7 weeks; prematurity<37 weeks=13; intra-uterine growth retardation=32%. Sixty-five percent neonates had withdrawal neonatal syndrome (WNNS) at a mean age of beginning at H40, mean highest Lipsitz score was 8.2 at H78. Half of the neonates with WNNS received treatment, mainly with morphine chlorhydrate. Neonatal mortality was 0/246. Discharge of the neonates was 60% with their father and their mother, and 32% with their mother alone; 4% were placed in foster homes by judicial decision. The only statistically significant differences between the MTD and HDB groups were: maintenance program was more frequently initiated before this pregnancy for the HDB vs MTD group (p<0.03); MTD maintenance was more often supervised by maintenance specialized centers and HDB by general practitioners (p<0.001); prematurity was 18% for MTD group vs 9% for HDB group (p<0.04); mean age of maximum Lipsitz score was H92 for MTD group vs H70 for HDB group (p<0.001). CONCLUSIONS: The perinatal medical and social prognosis of these 246 pregnant drug abusers and of their neonates appeared to be improved by the specialized prenatal care, comparatively with literature data. Perinatal impact of substitution program during pregnancy would be similar with MTD or HDB.

Analgesics, Opioid↗
PubMed2000

The inclusion of fluoxetine into gamma-cyclodextrin increases its bioavailability: behavioral, electrophysiological and pharmacokinetic studies.

The inclusion of a drug into cyclodextrin generally results in the modification of its physical and chemical properties and sometimes can increase its oral bioavailability. The aim of this study was to compare the effects of the fluoxetine HCl/gamma-cyclodextrin complex to that of traditional fluoxetine HCl. In the forced swimming test in mice, fluoxetine HCl/gamma-cyclodextrin was more effective than fluoxetine HCl, the ED30s being, respectively, 9.5 and 16.9 mg/kg PO. Both compounds (10 mg/kg PO) were able to reduce the firing rate of dorsal raphe neurons in the rat. However, between-groups comparisons showed no significant differences between fluoxetine HCl treated animals and the vehicle group, while fluoxetine HCl/gamma-cyclodextrin appeared significantly more effective than vehicle from minute 25 of the measurement period. In healthy volunteers, the relative oral bioavailability, calculated as the ratio AUC 0-infinity fluoxetine HCl/gamma-cyclodextrin on AUC 0-infinity fluoxetine HCl (20 mg PO), was equal to 249.9%. The three experiments taken together suggest that the complexation of fluoxetine HCl into gamma-cyclodextrin increases its pharmacological efficacy in animals, this effect being related to an enhancement of its oral bioavailability as demonstrated in human healthy subjects.

Adolescent↗
PubMed2000

[Effects of hormone replacement therapy for menopause on prognostic factors of breast cancer].

AIM: Hormone replacement therapy (HRT) is widely used by post-menopausal women. Although this treatment may slightly increase the incidence of breast cancer, more and more cases are diagnosed while women are taking HRT. The purpose of this study was to ascertain the influence of HRT on prognostic factors and outcome of breast cancer. Data on all breast cancer patients, including precise information on HRT, was prospectively and systematically recorded in a data base. PATIENTS AND METHODS: From 1990 to 1998, 1223 post-menopausal women fulfilled the eligibility criteria for this study. The clinical features, laboratory findings and survival rates in 245 HRT users who developed breast cancer while being treated were compared with those of 245 matched breast cancer patients who had never received HRT. RESULTS: Patients who developed breast cancer during HRT had fewer locally advanced cancers and smaller and better-differentiated cancers. Estradiol receptivity was quantitatively lower in users. Metastasis-free survival were better for the users. CONCLUSION: We conclude that HRT does not affect the prognosis of breast cancer. Regular surveillance during HRT allows early detection of smaller lesions. The higher number of well-differentiated cancers and the distribution of hormone receptivity may reflect interaction between neoplastic tissue and exogenous hormones.

Adult↗
PubMed2000

Family history and risk of colorectal cancer: implications for screening programmes.

OBJECTIVE: To estimate the lifetime risk of colorectal cancer in the general population and in first degree relatives of patients with sporadic colorectal cancer or adenoma. MAIN OUTCOMES MEASURES: The cumulative risk of colorectal cancer (0-74) in the general population combined with the relative risk of colorectal cancer and the prevalence of different groups of subjects with family history of colorectal tumour allows the calculation of cumulative risks in these groups. RESULTS: The lifetime risk of colorectal cancer was 1 in 23 in men and 1 in 40 in women. In males, 0.5% in the 55-59 age group and 4.5% in the 70-74 age group will develop a colorectal cancer. The corresponding values in females were 0.4% and 2.5%. The cumulative risk at age 74 varied between 7.7% (one family member affected) and 25.6% (two affected) in males, and 4.3% and 14.3% respectively in females. The risk in the 40-44 year age group for individuals with one first degree relative affected before 45 years of age was 0.5%, similar to that of those aged 45-49 with one first degree relative affected with a colorectal cancer or a large adenoma (> 1 cm). CONCLUSIONS: These results suggest that screening in the general population should start at 50 or 55. The lifetime risk is high enough (over 10%) among individuals with one affected first degree relative before age 45, or with at least two affected first degree relatives, to warrant colonoscopic screening. The data provide a basis for recommendations that relatives of these patients should enter screening programmes at age 40 to 44.

Adult↗
PubMed2000

[Neonatal withdrawal syndrome in twins born to a mother on methadone substitution].

We report the cases of two female twins whose mother was taking methadone substitution therapy. These cases demonstrate the unpredictable nature of the neonatal withdrawal syndrome. One baby developed signs of withdrawal late 10 days after birth. She had a less severe syndrome than her twin sister who was hypotrophic and developed signs on day 1 which persisted for 6 weeks.

Adult↗
PubMed1999

Prognostic factors in ductal carcinoma in situ of the breast: results of a retrospective study of 575 cases. The Association for Research in Oncologic Gynecology.

OBJECTIVE: Conservative treatment for ductal carcinoma in situ of the breast exposes patients to the risk of infiltrating recurrence which can lead to metastasis. The primary purposes of this retrospective study were to evaluate diagnostic and therapeutic methods over a 10-year period and to validate prognostic factors. This information should greatly improve patient selection for conservative treatment or mastectomy. STUDY DESIGN: A multi-institutional data base including 575 patients treated between 1983 and 1993 was established by combining data from 16 French institutions. Survival at 5 and 7 years was studied as a function of various prognostic factors. RESULTS: Recurrence-free survival at 7 years was 0.96 after modified radical mastectomy and 0.83 after breast-conserving treatment and radiotherapy (P=0.003). Metastasis-free survival at 7 years was 0.99 after modified radical mastectomy and 0.94 after breast-conserving treatment and radiotherapy (not significant). No factor was predictive of local recurrence after mastectomy. Clinical stage was the only factor significantly correlated with metastasis after mastectomy. Recurrence-free survival after breast-conserving treatment with radiotherapy was significantly lower for patients with comedo carcinoma, multifocal lesions, or unclear resection margins, regardless of whether the histological type was comedo or non-comedo carcinoma. Metastasis-free survival was significantly lower for patients with multifocal lesions and for patients with unclear margins after excision of comedo carcinoma. CONCLUSIONS: Breast-conserving treatment with radiotherapy is a valid alternative to mastectomy. Patients must be selected carefully on the basis of morphological criteria. Swift gains in therapeutic outcome can be obtained by stressing quality control at each stage of diagnosis and treatment.

Adult↗
PubMed1999

[Pneumothorax revealing cystic adenomatoid malformation of the lung in a 13 year old child].

CASE REPORT: A 13 year old boy had a seven day history of chest pain and dyspnea. His right hemithorax was immobile with abolished breathing sounds. Initial chest X-ray revealed a right tension pneumothorax. A chest tube was inserted and the right lung re-expanded. However, despite two intrapleural injections of tetracyclin, the pneumothorax reappeared. Lung CT scan showed an intraparechymal cyst in the posterior part of the right upper lobe. Lobectomy was performed and histological study confirmed the diagnosis of type I cystic adenomatoid malformation of the lung. Two months after surgery, clinical and radiological examinations were normal. CONCLUSION: Spontaneous pneumothorax, as the initial manifestation of cystic adenomatoid malformation of the lung, is rare (three cases reported in children beyond the neonatal period, and two in adults). CT scan features correlate well with the pathologic features. Because of the risk of recurrent pulmonary infections and malignancy change, removal of the cystic lesions is advisable.

Adolescent↗
PubMed1999

Faecal occult blood screening and reduction of colorectal cancer mortality: a case-control study.

To estimate the efficacy of screening on colorectal cancer mortality, a population-based case-control study was conducted in well-defined areas of Burgundy (France). Screening by faecal occult blood test prior to diagnosis in cases born between 1914 and 1943 and who died of colorectal cancer diagnosed in 1988-94 was compared with screening in controls matched with the case for age, sex and place of residence. Cases were less likely to have been screened than controls, with an odds ratio (OR) of 0.67 [95% confidence interval (CI) 0.48-0.94]. The negative overall association did not differ by gender or by anatomical location. The odds ratio of death from colorectal cancer was 0.64 (95% CI 0.46-0.91) for those screened within 3 years of case diagnosis compared with those not screened. It was 1.14 (95% CI 0.50-2.63) for those screened more than 3 years before case diagnosis. There was a negative association between the risk of death from colorectal cancer and the number of participations in the screening campaigns. The inverse association between screening for faecal occult blood and fatal colorectal cancer suggests that screening can reduce colorectal cancer mortality. This report further supports recommendations for population-based mass screening with faecal occult blood test.

Aged↗
PubMed1999

Interval cancers in a community-based programme of colorectal cancer screening with faecal occult blood test.

Interval cancers represent the major limitation of screening for colorectal cancer with the faecal occult blood test. The aim of this study was to describe the characteristics of interval cancers and the sensitivity of the screening programme in a well-defined French population. During five screening rounds, 398 cancers were diagnosed in those of the population having performed at least one screening test; 57.8% of them were interval cancers. The proportion of interval cancers was higher among cancers of the rectal ampulla (72.2%) than among cancers of other sites (52.9%) (P < 0.001). The proportion of TNM stage I and II were higher among screen-detected cancers (73.8%) than among interval cancers (57.4%). The overall sensitivity of the screening programme was 62.9% within 1 year, and 48.7% within 2 years. An improvement in the sensitivity of the faecal occult blood test for colorectal cancer screening is needed, without an unacceptable loss of specificity.

Aged↗
PubMed1999

[Performance of the Hemoccult test in the screening of colorectal cancer and adenoma. Results of 5 screening campaigns in Saône-et-Loire].

OBJECTIVES: The aim of this population-based study was to specify the positivity rate, the positive predictive value of Hemoccult test as well as the characteristics of the cancers and adenomas screened during the successive colorectal cancer screening campaigns. METHODS: This study focused on five colorectal cancer mass screening campaigns by Hemoccult test carried out between 1988 and 1996. The test was offered every two years to a cohort of subjects born between 1914 and 1943 and living in some districts of the Saône-et-Loire administrative area. RESULTS: The positivity rate of the test was higher in the first campaign (2.1%) than in the subsequent ones (mean 1.3%). It was also higher in males than in females and it increased with age. After a positive test, 85.4% of the subjects had a colonic exploration. The exploration rate was higher when the test was offered by general practitioners (88.0%) than when it was mailed (77.8%) (P < 0.01). Through this test, cancer was detected in 168 patients, and one adenoma or more in 414 patients. The positive predictive value was 11.4% for cancer, 17.1% for adenoma > or = 1 cm and 11.1 for adenoma < 1 cm. It was higher in males than in females and it increased with age. Depending on the campaigns, 35.9% to 47.3% of the subjects explored after a positive test had a cancer or an adenoma. The screened cancers or adenomas were more often localized in the sigmoid or the rectum. Three quarters of screened cancers were stage I or II (TNM classification). All together, 82.7% of cancers were treated with surgical resection for cure and 10.1% with endoscopic resection. CONCLUSIONS: This work confirms the feasibility of carrying out regular colorectal cancer screening campaigns, through which a few subjects can be selected for undergoing colonic explorations. These latter can detect a cancer or adenoma in 40% of cases.

Adenoma↗
PubMed1998

Impact of menopausal hormone-replacement therapy on clinical and laboratory characteristics of breast cancer.

Hormone-replacement therapy (HRT) is widely used by post-menopausal women. Although this treatment may slightly increase the incidence of breast cancer, more and more cases are diagnosed while women are taking HRT. The purpose of this study was to ascertain the influence of HRT on prognostic factors and outcome of breast cancer. Data on all breast-cancer patients, including precise information on HRT, was prospectively and systematically recorded in a data base. From 1985 to 1995, 1379 post-menopausal women fulfilled the eligibility criteria for this study. All were treated by us (P.B. and L.P.) in our ward of a large public hospital of Marseilles, France. The clinical features, laboratory findings and survival rates in 142 HRT users who developed breast cancer while being treated were compared with those of 284 matched never user breast-cancer patients. Patients who developed breast cancer during HRT had fewer locally advanced cancers and smaller and better-differentiated cancers. Lymph-node involvement was significantly less frequent in the user group than in the non-user group (non-significant). Estradiol receptivity was both qualitatively and quantitatively lower in users. There was no significant difference with regard to recurrence and metastasis-free survival and overall survival. We conclude that HRT does not affect the prognosis of breast cancer. Regular surveillance during HRT allows early detection of smaller lesions. The higher number of well-differentiated cancers and the distribution of hormone receptivity may reflect interaction between neoplastic tissue and exogenous hormones.

Adult↗
PubMed1998

Treatment of carcinoma of the uterine cervix with concomitant cisplatin, 5-fluorouracil and split course hyperfractionated radiotherapy.

To improve local and systemic control of bulky (>4 cm) and/or advanced primary cancer of the uterine cervix, 35 patients were treated with concomitant cisplatin (CDDP), 5-fluorouracil (5-FU) and split course hyperfractionated radiotherapy. Radiation was administered to the pelvis in five-day courses at a dose of 1.5 Gy twice daily every 21 days until a median dose of 45 Gy was reached. 15 Gy more were administered to involved parametrium or central tumor by external radiotherapy or brachytherapy. The irradiated zone was extended to include paraaortic lymph nodes if necessary. CDDP was administered at a dose of 20 mg m(-2) and 5 FU at a dose of 500 mg m(-2) from day one to day five of each course. The median number of combined treatment courses per patient was four (1-6). Local responses were obtained in 19 out of 24 patients in whom evaluation was feasible (i.e. who did not undergo surgery prior to combined therapy). Median survival was not attained with a median follow up of 33 months, three year overall survival was 62% and 52% in patients with local control and in the whole population respectively. Several patients with stage III and IV tumors achieved a very long survival. Acute toxicity was manageable but three patients required surgical repair of late radiation complications. This combined chemotherapy and radiotherapy resulted in good local control and did not rule out surgery.

Adult↗