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Biomedical subjects

L Ollivier

Publications and source records attributed to L Ollivier.

At least 37 records · Page 2Linked to original sources

[Imputable cutaneous eruption caused by ticlopidine after implantation of a coronary endoprosthesis: why not continue treatment?].

BACKGROUND: The decision to interrupt a ticlopidine regimen in a patient who develops an adverse effect can be particularly difficult when discontinuing the drug could lead to a high risk situation. CASE REPORT: A 64-year old patient developed a skin rash after taking ticlopidine for coronary artery stenting. Stopping ticlopidine could have led to stent occlusion and no alternative therapy seemed to be suitable. We therefore decided to carry on the treatment under close clinical surveillance. The skin signs rapidly resolved. DISCUSSION: This cases shows that ticlopidine may be continued in patients who develop an adverse skin reaction. The rapid involution of the cutaneous signs in our patient demonstrated that the risk of discontinuing treatment can be greater than that of continuing.

Angioplasty, Balloon, Coronary↗

[Reliability of the response rate in oncology: analysis of the causes for variation].

We evaluated the impact of an evaluation committee (EC) on patients' overall response status in a large multicenter trial in oncology. We identified reasons for disagreements between investigators and the EC. The Cancer Renal Cytokine (CRECY) study was a French multicenter trial that tested cytokine therapy in 489 patients with metastatic renal cell carcinoma. Objective response (OR) evaluation included medical imaging and was studied according to international guidelines. A blinded peer review of all responders and litigious cases was performed by an EC. Major disagreements occurred in 43% and minor disagreements in 10.5% of the reviewed files. The number of significant tumor responses was reduced by 23.2% after review by the EC. Reasons for disagreements included errors in tumor measurements, errors in selection of measurable targets, intercurrent diseases, and radiologic technical problems. These reasons for disagreements are analyzed and discussed. We conclude that all therapeutic trial results should be reviewed by peer analysis of all presumed responders by an EC. International guidelines for response evaluation should be updated by including more reliable methods of measurements and definition of minimal imaging procedures.

Antineoplastic Agents↗

The accuracy of marker-assisted selection for quantitative traits within populations in linkage equilibrium.

Using the concept of conditional coancestry, given observed markers, an explicit expression of the accuracy of marker-based selection is derived in situations of linkage equilibrium between markers and quantitative trait loci (QTL), for the general case of full-sib families nested within half-sib families. Such a selection scheme is rather inaccurate for moderate values of family sizes and QTL variance, and the accuracies predicted for linkage disequilibrium can never be reached. The result is used to predict the accuracy of marker-assisted combined selection (MACS) and is shown to agree with previous MACS results obtained by simulation of a best linear unbiased prediction animal model. Low gains in accuracy are generally to be expected compared to standard combined selection. The maximum gain, assuming infinite family size and all QTLs marked, is about 50%.

Genetic Linkage↗

Predictive factors for complete removal in soft tissue sarcomas: a retrospective analysis in a series of 592 cases.

BACKGROUND AND OBJECTIVES: In order to specify the indications for conservative surgery and preoperative therapeutic approaches of soft tissues sarcomas (STS), we looked for the clinico-pathological parameters associated with the failure to obtain a complete removal (CRm) of the tumor. METHODS: We retrospectively analyzed a series of 592 cases of primary non-metastatic STS. Surgery was performed in 495 cases as a primary treatment and in 88 cases after chemo- or radiotherapy. Nine patients were treated by chemotherapy-radiotherapy. In a univariate analysis, 20 parameters were tested for their association with CRm. A multivariate analysis was then used to define the independent parameters linked to the achievement of a CRm. RESULTS: In the univariate analysis, 15 parameters were found to be linked to the achievement of a CRm. Three of them proved to be independent in the multivariate analysis: T in the TNM classification, tumor location, and tumor necrosis. By the combination of these risk factors, four groups of patients were defined, with respective rates of CRm of 97% (no factor), 95% (one factor), 70% (two factors), and 48% (three factors). CONCLUSIONS: The achievement of a CRm after surgery of STS depends not only on the accessibility of the lesion, but also on tumor aggressiveness, a reflection of which is necrosis. The detection of necrosis by imaging procedures may thus help predicting the resectability of tumors and defining the indications for neoadjuvant therapies, likely to broaden the use of conservative surgery.

Adolescent↗

The use of selection experiments for detecting quantitative trait loci.

Gene frequency changes following selection may reveal the existence of gene effects on the trait selected. Loci for the selected quantitative trait (SQTL) may thus be detected. Additionally, one can estimate the average effect (alpha) of a marker allele associated with an SQTL from the allele frequency change (delta q) due to selection of given intensity (i). In a sample of unrelated individuals, it is optimal to select the upper and lower 27% for generating delta q in order to estimate alpha. For a given number of individuals genotyped, this estimator is 0.25i2 times more efficient than the classical estimator of alpha, based on the regression of the trait on the genotype at the marker locus. The method is extended to selection criteria using information from relatives, showing that combined selection considerably increases the efficiency of estimation for traits of low heritability. The method has been applied to the detection of SQTL in a selection experiment in which the trait selected was pig litter size averaged over the first four parities, with i = 3. Results for four genes are provided, one of which yielded a highly significant effect. The conditions required for valid application of the method are discussed, including selection experiments over several generations. Additional advantages of the method can be anticipated from determining gene frequencies on pooled samples of blood or DNA.

Animals↗

Response rate accuracy in oncology trials: reasons for interobserver variability. Groupe Français d'Immunothérapie of the Fédération Nationale des Centres de Lutte Contre le Cancer.

PURPOSE: We evaluated the impact of an evaluation committee (EC) on patients' overall response status in a large multicenter trial in oncology. We identified reasons for disagreements between investigators and the EC. MATERIALS AND METHODS: The Cancer Renal Cytokine (CRECY) study was a French multicenter trial that tested cytokine therapy in 489 patients with metastatic renal cell carcinoma. Objective response (OR) evaluation included medical imaging and was studied according to international guidelines. A blinded peer review of all responders and litigious cases was performed by an EC. RESULTS: Major disagreements occurred in 40% and minor disagreements in 10.5% of the reviewed files. The number of significant tumor responses was reduced by 23.2% after review by the EC. Reasons for disagreements included errors in tumor measurements, errors in selection of measurable targets, intercurrent diseases, and radiologic technical problems. These reasons for disagreements are analyzed and discussed. CONCLUSION: We conclude that all therapeutic trial results should be reviewed by peer analysis of all presumed responders by an EC. International guidelines for response evaluation should be updated by including more reliable methods of measurements and definition of minimal imaging procedures.

Clinical Trials as Topic↗

[Physician-patient relationship in oncologic ultrasonography. The right way to inform the patient].

PURPOSE: Analysis of the doctor-patient relationship in oncologic sonography. MATERIAL AND METHOD: Two sonographers working in two different cancer institutes, one psychiatrist and one oncologist analyzed the various aspects of the relationship with cancer patients during sonographic examinations. RESULTS: Sonographers are in close contact with patients and are often the first to discover any abnormalities. They do not have any special training in psychopathology and know nothing about the patient's psychological profile. They cannot hide the truth nor deliver a sentence without also proposing a therapeutic solution. Their approach must be coherent with that of the attending physician to avoid increasing the patient's anxiety. CONCLUSION: An adapted approach to the patient must be based on personal experience, ethical guidelines, listening to the patient and collaboration with other members of the medical team.

Anxiety↗

Genetic differences in recombination frequency in the pig (Sus scrofa).

A comparison has been performed on 3 recently published linkage maps of the pig, hereafter designated as the American (A), European (E), and Swedish (S) maps. The cumulated distances between common markers in these 3 maps were in the ratio 1.00 (A):0.88 (E):0.77 (S), in keeping with the ratio of the percentages of domestic genome in the reference families used to build the corresponding maps, i.e., 1.00 (A):0.81 (E):0.50 (S). From further recombination frequencies reported in wild boars (in the S report), the wild pig genome length (in centimorgans) is expected to represent 66% of the domestic pig genome length. These observations tend to confirm a general result of Burt and Bell (Nature (London), 326: 803-805 (1987)), showing higher chiasma frequencies in domestic mammalian species compared with wild species. Consequences for mapping studies are discussed.

Animals↗

[Imaging of osteosclerotic metastases].

Carcinomas of the prostate and breast are the most common sources of osteosclerotic metastases. The osteoblastic response is related to stromal bone formation and reactive bone formation. Purely osteosclerotic or mixed osteolytic-osteosclerotic lesions are encountered. Frequent differential diagnoses are enostoses and Paget's disease. The classical MRI pattern is a signal of low intensity on T1 and T2- weighted sequences, but some osteoblastic metastases have an inhomogenous signal. Evaluation of the response to treatment is difficult and requires confrontation with clinical and biological data.

Bone Neoplasms↗

Heart rate variability in two models of cardiac hypertrophy in rats in relation to the new molecular phenotype.

The analysis of heart rate variability (HRV) provides information on neural control of the heart. We investigated HRV in normal rats and in models of experimental cardiac hypertrophy using the Holter monitoring and peak/trough method. In normal rats, two heart rate oscillations with different wavelengths, high frequency (HF) and low frequency (LF) oscillations, were detected. The HF oscillations were insensitive to propranolol and suppressed by atropine. The LF oscillations were sensitive to both antagonists. Thyrotoxicosis resulted in cardiac hypertrophy (+20%) and tachycardia. The HF oscillations were unchanged, whereas LF oscillations were hampered at low heart rate in this group. Aortic stenosis resulted in cardiac hypertrophy (+53%), but heart rate oscillations were unchanged. The (number x amplitude) product for both types of oscillations correlated with heart rate in controls but not in the thyrotoxicosis or aortic stenosis models. Alterations of HRV in cardiac hypertrophy occur in rats as in humans. They may reflect the changes in the molecular components of the adrenergic/muscarinic system, which defines the new myocardial phenotype.

Analysis of Variance↗

[Ovarian steroid cell tumors: a bilateral form].

The authors report a case of bilateral ovarian steroid cell tumour, not otherwise specified (as subclassified now by Scully). For two years a 46-year-old woman had androgenic manifestations. Only plasma testosterone level was increased. A hysterectomy with bilateral ovariectomy was performed. The first diagnosis was bilateral Leydig cell tumour, but no Reinke crystal was found. The final diagnosis was steroid cell tumour, not otherwise specified. No significant nuclear atypia or mitotic activity were found and two-year follow-up was favourable. The authors discuss the difficulty to class some ovarian tumours between Leydig cell tumour and steroid cell tumour, not otherwise specified as defined by Scully.

Diagnosis, Differential↗

A note on the estimation of the effective number of additive and dominant loci contributing to quantitative variation.

A method of estimating the number of loci contributing to quantitative variation has been proposed by S. Wright in 1921. The method makes use of the means of inbred lines and the variances of their F1, F2 and backcrosses. The method has been extended to crosses between outbreeding populations by R. Lande in 1981. Additive gene action is one of the major assumptions required for obtaining valid estimates. It is shown here that this assumption may be relaxed. One can estimate both a total number of effective loci and a number of dominant loci (the latter only when the parents are inbred) by comparing the variances of the F1, F2 and backcrosses. Numerical illustrations are given, based on crossbreeding data.

Animals↗

Evidence for linkage between K88ab, K88ac intestinal receptors to Escherichia coli and transferrin loci in pigs.

Segregation at the loci coding for the K88ab and K88ac small intestinal receptors to E. coli adhesins (K88abR, K88acR) and at the transferrin (TF) locus was studied in 38 pig families including 273 piglets. The TF locus showed a segregation deviation towards the B variant while each of the K88 receptors behaved as a single autosomal dominant gene. Recombinants between K88abR and K88acR provide evidence that they are under the control of two different loci. Thirty-two triple backcross families were selected to test linkage and estimate recombination rates (theta). Our results demonstrate that the two K88 receptor loci are closely linked (theta = 0.02) with a maximum lod score value (Zm) of 46.0. In addition, they are linked to the TF locus, theta = 0.14, Zm = 19.6 for the K88abR locus and theta = 0.16, Zm = 17.9 for the K88acR locus. The estimated recombination rates, smaller in males than in females, are consistent with the order TF-K88abR-K88acR. This linkage thus localizes the K88 loci, as the TF locus, on chromosome 13.

Adhesins, Escherichia coli↗

[Evaluation of second look laparotomy in the management of epithelial ovarian tumors. 88 interventions performed at the Dijon CAC between 1979 and 1990].

OBJECTIVE: To evaluate the second look laparotomy in the treatment and management of epithelial ovarian carcinoma. DESIGN: A retrospective study (1979-1990). SETTING: Centre G.-F. Leclerc, Dijon. SUBJECTS: 88 patients underwent a 2e look laparotomy during the period. Most of them (69.3%) were stage III or IV cancers. RESULTS: The predictive value of a negative second look is of evidence: 5 years survival of 63% versus 4% if residual tumor is observed. Nevertheless the therapeutic value of a tumoral exenteration during the second look is not demonstrated: the 5 years survival is only of 7% for these patients. CONCLUSIONS: This study demonstrates the importance of an appropriate surgery during the first look in the management of ovarian tumors. The contribution of the second look is primarily a prognostical contribution.

Actuarial Analysis↗

[Ewing's tumor].

Ewing's tumour is an undifferentiated round-cell sarcoma of children and adolescents arising from the skeleton. The translocation (11; 22) (q24; q12) is specific and could serve as a diagnostic marker. It has also enabled this tumour to be classified in the group of primary neuro-ectodermal tumours. Concerning treatment, intensive chemotherapy alternating with local therapy has improved the prognosis of localized Ewing's sarcoma of the limbs and, to a lesser degree, of the axial skeleton.

Bone Neoplasms↗

Spontaneous arrhythmias in various models of cardiac hypertrophy and senescence of rats. A Holter monitoring study.

OBJECTIVE: The aim was to define experimental models of spontaneous arrhythmias in various models of cardiac hypertrophy in rats. METHODS: Cardiac hypertrophy was induced by several methods and 24 h Holter monitoring was recorded in conscious rats to quantify spontaneous arrhythmias in hypertrophied hearts. Male Wistar rats were studied. A group of young controls 1-2 months old (n = 16) was compared to four groups of animals with cardiac hypertrophy: (1) thyrotoxic rats which received a daily intraperitoneal injection of L-thyroxine for 7 d (n = 6); (2) rats subjected to abdominal suprarenal aortic stenosis (n = 11); (3) senescent rats 22-24 month old (n = 6); and (4) S-DOCA-salt (senescent animals rendered hypertensive by uninephrectomy and DOCA-salt treatment, n = 8). RESULTS: (1) Thyroxine resulted in 20% cardiac hypertrophy, with normal arterial tension, sinus tachycardia, a shorter P wave length and PR interval, and frequent (5/6) atrioventricular block. No premature beats were seen. (2) In aortic stenosis, atria and left ventricle were hypertrophied by 53% and systolic carotid pressure increased by 63%. The incidence of supraventricular premature beats was increased [frequency = 0.70 (SEM 0.3) per 24 h in control v 99(61) in aortic stenosis, p < 0.05]. Ventricular premature beats remained as rare as in control. (3) In senescent and S-DOCA-salt rats all types of spontaneous arrhythmias, but specially supraventricular arrhythmias and atrioventricular block, were frequent. Cardiac hypertrophy produced by DOCA-salt treatment in senescent rats had no effect on the incidence and nature of arrhythmias, but resulted in an increased QTc interval. CONCLUSIONS: Senescent rats and rats with aortic stenosis represent valid models of spontaneous arrhythmias occurring in the absence of ischaemia or toxic insult. Spontaneous arrhythmias in rats are mainly of supraventricular origin. Hyperthyroidism in rats is a model of atrioventricular block probably related to tachycardia. Holter monitoring in rats may have several potential pathophysiological and pharmacological applications.

Aging↗

Mammographic features of 455 invasive lobular carcinomas.

Of 6,009 cases of breast cancer studied, 455 (7.6%) were invasive lobular carcinoma (ILC); 341 of these (75%) were pure ILC and 114 (25%) were ILC mixed with ductal forms. The mammographic features were compared with those of the 5,554 other breast carcinomas. Pure ILCs were less frequently round (1% vs 11%) and more frequently spicular (28% vs 23%) or with architectural distortion (18% vs 6%) than the other breast carcinomas. Microcalcifications were less common (24% vs 41%) and retraction of the skin (25% vs 21%) and nipple (26% vs 17%) was more common in pure ILC than in the other breast carcinomas. When complementary magnification views were obtained, only 50% were helpful in diagnosis of ILC while 75% were helpful in diagnosis of other breast carcinomas. Malignancy was less frequently diagnosed in ILC (57%) than in the other breast carcinomas (64%). The results were intermediate in the mixed ILC group.

Adult↗