PubMed Health⌕ Search

Biomedical subjects

C Varin

Publications and source records attributed to C Varin.

16 recordsLinked to original sources
PubMed2006

Molecular profiling of bladder tumors based on the detection of FGFR3 and TP53 mutations.

PURPOSE: On a routine basis we performed systematic molecular screening for FGFR3 and TP53 mutations in 121 bladder tumors. We then specifically analyzed the predictive value of the recurrence of FGFR3 and TP53 genotypes in superficial lesions. MATERIALS AND METHODS: The FGFR3 gene was analyzed by direct sequencing of exons 7, 10 and 15, whereas TP53 status was determined using the p53 functional assay in yeast. RESULTS: We identified a missense FGFR3 mutation in 66% of pTa, 26% of pT1 and 12% of pT2 tumors. Of activating FGFR3 mutations 54% and 85% were found in low G1 and intermediate G2 grade tumors, respectively, but in only 20% of high grade G3 tumors. We detected inactivating TP53 mutations in 10% of pTa, 42% of pT1 and 58% of pT2 tumors. Moreover, TP53 mutations were found only in 23% of grade G1 and 3% of grade G2 tumors but in 44% of high grade G3 tumors. When the 2 genotypes were combined, we observed that 58% of pTa tumors had the (mutant FGFR3, WT TP53) genotype, whereas 58% of invasive lesions harbored the inverse genotype (WT FGFR3, mutant TP53). The (mutant FGFR3, WT TP53) genotype and the (WT FGFR3, mutant TP53) genotype were detected in 23% and 38% of pT1G3 tumors, respectively. In the subgroup of 92 patients with superficial pTa-T1 bladder tumors we did not find that the TP53 or FGFR3 genotype alone or combined had a predictive value for tumor recurrence. CONCLUSIONS: Our data again represent solid proof for the pivotal role of FGFR3 and TP53 mutations in superficial and invasive bladder tumors, respectively. However, other molecular markers should be identified for borderline pT1G3 bladder tumors, which are probably at the crossroads of these 2 distinct molecular pathways.

Aged↗
PubMed2004

[Section planes for cardiac MRI].

The recent developments of synchronized cardiac MRI are a unique opportunity for the radiology community to integrate cardiac imaging. This educational aticle aims to help radiologists and technicians to obtain cardiac planes comparable to those of cardiac ultrasound and gated SPECT. Of course, cardiac planes described herein for MRI also apply to multi-detector CT.

Aorta, Thoracic↗
PubMed1999

Efficacy and acceptability of intranasal 17 beta-oestradiol for menopausal symptoms: randomised dose-response study. Aerodiol Study Group.

BACKGROUND: The benefit of oestrogen therapy for menopause symptoms is well recognised. However, the means of delivery currently available have disadvantages, including variable bioavailability, intestinal and hepatic first-pass effects, and dermatological reactions. An intranasal 17beta-oestradiol spray, S21400, which bypasses such drawbacks, has been developed. We studied the efficacy and tolerability of S21400 in the treatment of postmenopausal symptoms. METHODS: In this double-blind study, 420 postmenopausal women were randomly allocated to receive intranasal placebo or S21400 in doses of 100 microg, 200 microg, 300 microg, or 400 microg, or oral oestradiol valerate in doses of 1 mg or 2 mg, daily for 12 weeks. The primary outcomes were the Kupperman Index (KI) and the incidence of hot flushes. Tolerability assessments included rhinoscopy and ciliary function tests. FINDINGS: S21400 dose-dependently decreased KI (p<0.001), with a lowest effective dose of 300 microg/day at 4 weeks (p<0.05) and 200 microg/day at 12 weeks (p<0.01). The incidence of hot flushes decreased by a maximum of 75% (S21400 lowest effective dose 200 microg/day at 4 weeks and 100 microg/day at 12 weeks). S21400 increased serum oestradiol exposure dose-dependently, to concentrations similar to those achieved with oral oestradiol 1-2 mg, with lower intra-patient and inter-patient variability. There was no significant difference in ear, nose, and throat function or adverse events between the S21400 and the placebo or oral oestradiol groups, except for a greater incidence of sneezing and application site reaction (99% mild or moderate) in the S21400 groups. S21400 was thought to be effective and convenient by the patients, and compliance was high. INTERPRETATION: Intranasally administered 17beta-oestradiol is significantly better than placebo; its effectiveness at reducing menopausal symptoms is similar to that of oral oestradiol and is also well-tolerated. Intranasal administration avoids first-pass metabolism and provides a reproducible, easily adjustable dosing mechanism that represents a new option for hormone replacement therapy.

Administration, Intranasal↗
PubMed1999

Effects of intranasal 17beta-estradiol on bone turnover and serum insulin-like growth factor I in postmenopausal women.

Estrogen therapy, using either oral or transdermal routes, decreases bone turnover and prevents postmenopausal bone loss. It has been suggested that oral and transdermal 17beta-estradiol (E2) may have different effects on serum insulin-like growth factor I (IGF-I), a potent bone-forming growth factor. In this study we investigated the effects of a new route of administration, the intranasal E2 spray (S21400), on bone turnover and circulating IGF-I and IGF-binding protein-3 (IGFBP-3). Four hundred and twenty early postmenopausal women (<5 yr since menopause; mean age, 52 yr) were enrolled in a 3-month, double blind, placebo-controlled study of four doses of intranasal E2 (100, 200, 300, and 400 microg/day), two doses of oral E2 valerate (1 or 2 mg/day), and placebo. One hundred and twelve women were further treated for 12 months with intranasal E2 (300 microg/day, i.e. the dose that has been shown to be adequate for the majority of postmenopausal women). Markers of bone resorption (urinary type I collagen C telopeptides) and formation [serum osteocalcin, serum type I collagen N-terminal extension propeptide (PINP), and serum bone alkaline phosphatase (BAP)] were measured at baseline, 1 month, 3 months, and 15 months. Serum IGF-I and IGFBP-3 were measured at baseline, 1 month, and 3 months. Urinary type I collagen C telopeptides decreased significantly in all active treatment groups as soon as 1 month (P<0.001 vs. placebo) and continued to decrease at 3 months with a dose effect for intranasal E2. Serum osteocalcin and PINP did not change at 1 month for oral E2 (1 and 2 mg), but decreased significantly at 3 months. In contrast, formation markers increased significantly at 1 month for the two highest doses of intranasal E2 (P<0.01 vs. placebo for osteocalcin and BAP) and did not decrease at 3 months. Oral E2 induced a marked decrease in circulating IGF-I as early as 1 month, which was amplified at 3 months (-29% and -32% for 1 and 2 mg, respectively), whereas no significant change from placebo was observed for intranasal E2 during the 3-month period. Changes in circulating IGF-I correlated significantly (P<0.01) with changes in osteocalcin, PINP, and BAP at 3 months. Oral and intranasal E2 did not induce any significant change from placebo in serum IGFBP-3 at both 1 and 3 months. After 1 yr of treatment with intranasal E2 (300 microg/day), both resorption and formation markers decreased, reaching the levels in premenopausal women, regardless of the type of treatment during the first 3 months. We conclude that E2 administered by this new nasal route normalizes bone turnover to premenopausal levels. The delayed decrease in bone formation observed with intranasal E2 compared to oral E2 may be related to different effects on serum IGF-I levels.

Administration, Intranasal↗
PubMed1993

[Diagnostic and therapeutic strategy in coronary insufficiency in the elderly. Apropos of 65 cases].

As people live longer, so cardiologists are having to manage coronary artery disease in progressively older patients with more severe coronary lesions. The authors tried to determine the feasibility and results of coronary angiography in a retrospective study of 65 patients (44 men and 21 women) over 75 years of age (range 75 to 84 years) with coronary artery disease (excluding valvular heart disease). The study period was 22 months. The commonest indication was unstable or invalidating angina resistant to medical therapy (42 of the 65 cases). Twenty-two patients underwent coronary angiography in the context of myocardial infarction complicated in 3 cases by septal rupture. With the exception of these 3 patients, two of whom underwent surgery, 39 of the 62 remaining patients were judged to be candidates for myocardial revascularisation (63%); 37 underwent a revascularisation procedure (60%), 20 by percutaneous transluminal coronary angioplasty and 17 by coronary bypass surgery. The primary success rate of angioplasty was 90% (18 out of 20). There were no deaths in this group. Two patients who were referred for surgery died, an operative mortality of 12% (2 out of 17). All patients were followed up: 56 out of the 65 were still alive at the time of enquiry, after an average period of 18 months. All surviving patients who were successfully revascularised (by angioplasty or surgery) were pauci- or asymptomatic. Although there is an increased mortality related to revascularisation of elderly patients, this would seem to be acceptable given the quality of the medium term clinical results.

Aged↗
PubMed1993

[Left intraventricular dynamic gradients in the follow-up of aortic valve replacement: an echo-Doppler study].

The possibility of an intraventricular pressure gradient in patients with aortic stenosis is well known: this entity is associated with a high risk of postoperative complications. The authors carried out a Doppler echocardiographic study of flow in the left ventricle in 51 patients who had recently undergone valve replacement for severe aortic stenosis (valve area < 0.75 cm2). Before surgery, only one patient had significant acceleration of intraventricular systolic flow attaining 3.8 m/s (maximum pressure gradient of 60 mmHg). After surgery, maximum intraventricular systolic velocities of over 2.5 m/s with a typical end systolic peak were observed in 8 patients under basal conditions (gradients of 30 to 115 mmHg), and in 7 others after inhalation of amyl nitrite. Pulsed spectral and color Doppler flow mapping showed that the highest velocities were located at the mitral papillary muscle level. In addition, these patients had significant reduction in cavity size. Only one patient had systolic anterior motion of the anterior mitral leaflet with septal contact. Left ventricular dimensions were measured by TM echocardiography. High intraventricular velocities seemed to be significantly related to the smallest ventricular dimensions, the thickest ventricular walls and the smallest preoperative aortic valve surface area. The highest intraventricular pressure gradients-disappeared with betablocker therapy (4 cases), after correction of hypovolemia (1 case), after drainage of large pericardial effusions (2 cases) or spontaneously (1 case). This study confirms the relatively high prevalence of dynamic intraventricular gradients after surgical cure of aortic stenosis and the value of Doppler echocardiography for the avoidance of certain drugs (inotropic agents, vasodilators, diuretics), which could aggravate the hemodynamic abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effect of the progestagen R5020 (promegestone) and of progesterone on the uptake and on the transformation of estrone sulfate in the MCF-7 and T-47d human mammary cancer cells: correlation with progesterone receptor levels.

In the present study we have explored the actions of the progestagen R5020 (Promegestone: 17 alpha, 21-dimethyl-19-nor-pregna-4, 9-diene-3,20-dione) and progesterone on the uptake of [3H]estrone sulfate ([3H]E1S) and its conversion to estradiol (E2) by two hormone-dependent mammary cancer cell lines: MCF-7 and T-47D. R5020 or progesterone significantly decreased the uptake of [3H]E1 and its conversion to (E2). In the cells of the two lines, R5020 or progesterone (5 x 10(-6) M) decreased the E2 concentrations by 2-3 times in relation to the levels in untreated cells. E1S (1 x 10(-7) M) also increased expression of the progesterone receptor (PR) and both R5020 (5 x 10(-6) M) and progesterone (5 x 10(-6) M) blocked this stimulatory action of E1S in cells of both cell lines. As E2 is one of the main factors of cancerization in the breast and estrone sulfate is quantitatively the most important precursor of E2 in this tissue, the decrease of E2 by these progestagens could open new possibilities for the control of E2 in the breast cancer tissue.

Biotransformation↗
PubMed1992

Double-blind trial of promegestone (R 5020) and lynestrenol in the treatment of benign breast disease.

One hundred thirty-two women between the ages of 19 and 50, with various forms of benign breast diseases received 1 mg promegestone, or 0.5 mg promegestone, or 10 mg lynestrenol daily (double-blind), for 15 days per cycle, during three cycles. The groups were identical before treatment, with the exception of a longer history of mastodynia and mastopathies in the 1 mg promegestone group than in the lynestrenol group (P = 0.04) and a greater proportion of mastosis zones in the lynestrenol group as compared to the 0.500 mg promegestone group (P = 0.05). The effectiveness of lynestrenol both in terms of symptomatology (evaluated as good or excellent in 66.6% of the cases) and of clinical observations (evaluated as good or excellent in 59% of the cases) is not significantly different statistically from that of promegestone at 1 mg, whose effectiveness on symptomatology was good or excellent in 65.9% and 57.1% of the cases, respectively, or from that of promegestone at 0.5 mg/day (with 65% and 51.3% effectiveness, respectively). Clinical tolerance was rated good or excellent for 73.9% of the women on 1 mg promegestone and for 59.5% of the women on 0.500 mg promegestone, compared to 66.7% of the women on lynestrenol. No statistically significant difference was observed, neither between lynestrenol and promegestone 1 mg nor between lynestrenol and promegestone 0.5 mg. This study shows a clear improvement in functional and physical signs in patients treated with promegestone. Promegestone's efficacy is close to that of lynestrenol, a nonsteroidal progestin.2+ off

Adult↗
PubMed1992

Prevalence of colorectal polyps in Filipinos. An autopsy study.

From May 1988 to May 1990, a prospective autopsy study was performed in patients who died at the Philippine General Hospital in Manila, Philippines. Patients younger than 10 years of age, patients with a history of large bowel resection, and patients whose deaths were related to trauma were excluded. There were 416 patients; 246 were males, and 170 were females. The mean age was 47 years (range, 11-95 years). Six of the 416 patients (1.4 percent) were found to have polyps. One patient had an inflammatory polyp, one was diagnosed with familial adenomatous polyposis, and one had an associated cecal carcinoma. Five "sporadic" adenomatous polyps were found in the remaining three patients (prevalence rate, 0.7 percent). All of the adenomatous polyps were located distal to the hepatic flexure and exhibited only mild atypia. The mean size was 6.4 mm (range, 2-20 mm). The incidence of colorectal adenomas in Filipinos is low compared with that in age-adjusted Western populations. This finding coincides with a low incidence of colorectal carcinoma. The documentation of a low risk for adenomatous polyps and colorectal cancer indicates that it would be difficult for massive screening programs to demonstrate a significant positive impact on the early detection of colorectal neoplasias in the Filipino general population.

Adolescent↗
PubMed1992

Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer.

Of the total number of breast cancers approx. 30-50% are hormone-dependent and estradiol is one of the main factors of cancerization. Consequently, the control of this hormone inside the cancer cell is of capital importance because it is well established that the inhibition of estradiol biosynthesis can have a positive effect on the evolution of the disease. The blockage of estradiol can be obtained by the action of anti-aromatases, anti-sulfatases, the control of the 17 beta-hydroxysteroid dehydrogenase activity or by the stimulation of the sulfotransferase which converted the estrogens in their sulfates. In breast cancer tissue estrone sulfate is quantitatively the most important source of estradiol. In the intact cell, estrone sulfatase activity is very intense in the hormone-dependent cell lines (e.g. MCF-7, T-47D) but very small activity is observed in the hormone-independent (e.g. MDA-MB-231, MDA-MB-436) cell lines. However, this activity became very strong after homogenization in the hormone-independent cells, suggesting the presence of repressive factor(s) for this enzyme or its sequestering in an inactive form, in the intact cells of these cell lines. In a series of previous studies it was found that in hormone-dependent cell lines different anti-estrogens: tamoxifen and derivatives, ICI 164,384, very significantly decrease the estradiol concentration originated from estrone sulfate, and recently it was observed that Decapeptyl (D-Trp6-gonadotropin-releasing hormone) in the presence of heparin can also decrease the conversion of estrone sulfate into estradiol. No significant effect was obtained in the presence of heparin or Decapeptyl alone. The estrone sulfatase activity can be inhibited by progesterone, the progestagen R-5020, and testosterone. In another series of recent studies the presence of very strong estrogen sulfotransferase activity has been shown in one breast cancer cell line, the MDA-MB-468. We can conclude that: (1) the control of estradiol concentration can be carried out in the breast cancer tissue itself; (2) estrone sulfate can play an important role in the bioavailability of estradiol in the breast cancer cell; and (3) as is the case for the aromatase, the control of: the estrogen sulfatase, estrogen sulfotransferase, and 17 beta-hydroxysteroid dehydrogenase can be new targets for therapeutic applications in breast cancer.

Breast Neoplasms↗
PubMed1992

[Radiofrequency ablation of atrioventricular conduction during the 5th month of pregnancy].

The authors report the case of radiofrequency ablation of atrioventricular conduction in a 5 months pregnant woman who had hypertrophic cardiomyopathy. The indication of this procedure was a poorly tolerated resistant supraventricular tachycardia with foetal distress. A dual-chamber rate-assisted pacemaker programmed in the VVIR mode was implanted during the same procedure normally, with normal delivery of a healthy child at 8 months' gestation.

Adult↗
PubMed1992

[Doppler echocardiography and double chamber pacing].

Doppler-echocardiography is playing an increasing role in cardiac pacing: 1) Before implantation, to determine any cardiac disease possibly accompanying the conduction disturbance, and the quality of atrial function in order to identify the appropriate indications for the type of pacing which will restore normal AV synchronism. Alongside morphometric data (size of atria, etc.), this analysis is based above all on the evaluation of LV filling flows and ejection, if necessary during provisional pacing in DRV mode. It is important to be aware of and prevent certain problems: 1st degree AV block with very long PR, high degree interatrial conduction disturbances, etc. 2) To evaluate the possible benefits of pacing in certain new indications, e.g. obstructive hypertrophic cardiomyopathy (measurement of intra-LV gradient in sinus rhythm and with DRV pacing with total ventricular capture). 3) After implantation, to optimise the programming of double-chamber pacemakers and in particular AV intervals (base-line AV interval with paced atrial cycle, AV interval with detected atrial cycle, hysteresis of AV interval corresponding to the difference between the two previous values, slope of automatic variation in AV interval during exercise, etc.). Individual programming of these parameters based upon analysis of transmitral and ejection flow rates, at rest and, if necessary, during exercise, enables the optimisation of cardiac function (which is above all useful in the presence of concomitant organic heart disease) while at the same time improving the electrophysiological behaviour of the pacemaker at high frequencies.

Cardiac Pacing, Artificial↗
PubMed1992

[Value of an algorithm of automatic adaptation of the atrio-ventricular delay to the instantaneous atrial rate in cardiac stimulation].

It has been suggested that an algorithm of automatic adaptation of the AV delay to the instantaneous atrial rate be introduced into the program of DDD pacemakers to reproduce the physiological adaptation of the PR interval to effort, characterised by progressive shortening inversely linearly related to the heart rate. In order to evaluate the potential benefits in conditions of "standard" programming (basal AV delay the same for all patients: maximal frequency of 1/1 AV synchronisation uniformly limited to 120 bpm), a haemodynamic study was undertaken in 10 patients who had permanent DDD pacemakers implanted for advanced AV block. Measurements were taken during two standardized exercise stress tests (20 W/2 mn steps from an initial load of 20 W) performed in a random order, one with a fixed AV delay of 156 ms and the other with an "automatic AV delay" allowing linear reduction from a maximum value of 156 ms at rest to a minimum value of 84 ms at the maximum heart rate of 120 bpm. At the peak of exercise the "automatic AV delay" significantly affected 4 parameters: the paced ventricular rate (p = 0.008) and rate-pressure product (p = 0.005) which increased, pulmonary capillary pressure (p = 0.03) and cycle-to-cycle variability of systolic and diastolic blood pressures (p = 0.02 < p < 0.0001) which decreased. There was a tendency (NS) to slowing of the spontaneous atrial rate and to increase in cardiac output. This increase was significant in some patients and seemed to be due to a good relationship between the individual optimal value of the value basal AV delay measured by Doppler echocardiography and the value programmed in this study (156 ms).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1985

In vivo effects of progestins on prolactin secretion.

To assess a possible inhibitory effect of progestins on PRL secretion, serum PRL and estradiol levels were determined in 13 women with hyperprolactinemia due to a pituitary microadenoma before and after 3 months of treatment with a potent progestin, lynestrenol. PRL levels also were assessed during a TRH challenge test before and after treatment. Results were compared to those obtained in 10 normal women studied during the early follicular phase of their menstrual cycle and at the end of 3 months of treatment. The PRL response to TRH was blunted in patients before lynestrenol therapy. After therapy, basal serum PRL levels were significantly decreased, and the response to TRH was almost abolished. No change occurred in the normal women. The estradiol level was 80.5 +/- 7.5 (+/- SEM) pg/ml in patients before treatment and decreased to 29.2 +/- 5.0 pg/ml after therapy. Therefore, lynestrenol, a potent 19-nortestosterone derivative, exhibits in vivo an anti-PRL effect that could be related to its antiestrogenic and/or androgenic activities.

Adenoma↗
PubMedDate not supplied

Effect of promegestone, tamoxifen, 4-hydroxytamoxifen and ICI 164,384 on the oestrone sulphatase activity of human breast cancer cells.

In the present study, we explored the effects on sulphatase activity by Promegestone (R-5020), Tamoxifen (TAM), 4-hydroxytamoxifen (4-OH-TAM) and ICI 164,384 in the T-47D hormone-dependent and MDA-MB-231 hormone-independent mammary cancer cell lines. Using homogenates of these cells it was observed that Promegestone has a significant effect on the inhibition of oestrone (E1) sulphatase activity. As this effect is competitive, it is suggested that there is a direct action of this compound on the enzyme. Tamoxifen has very little or no effect, 4-hydroxytamoxifen has an intermediate effect and ICI 164,384 is active in the enzyme inhibition, particularly with MDA-MB-231 cells. The present data could open new possibilities for human breast cancer treatment, as sulphatase is very active in the first step of the conversion of oestrone sulphate (E1S) to oestradiol (E2), and oestradiol is one of the principal carcinogenic factors in human hormone-dependent breast cancer.

Binding, Competitive↗