Biomedical subjects

S Legrain

Publications and source records attributed to S Legrain.

At least 19 recordsLinked to original sources

PubMed2003

[Cutaneous lymphangitic carcinomatosis and acquired ichtyosis associated with prostatic carcinoma].

BACKGROUND: Prostatic adenocarcinoma is exceptionally associated with cutaneous lesions. We describe a patient with cutaneous lymphangitis and paraneoplastic ichtyosis related to prostatic cancer. CASE REPORT: A 92 year-old man had been treated for five years for a prostatic carcinoma. An angiomatous lesion developed with in 3 months near the right breast. Physical examination revealed axillary node enlargement, a large skin angiomatous lesion, and ichtyosis. The skin biopsy of the angiomatous skin lesion demonstrated its prostatic origin with carcinomatous metastases in the lymphatic vessels. The ichtyosis was considered as paraneoplastic. DISCUSSION: Cutaneous metastases from prostatic carcinoma are rare. Less than 1 p. 100 of cutaneous metastases are of prostate origin despite the high frequency of this cancer in the general population. The clinical aspects - angiomatous lesion and paraneoplastic ichtyosis - are exceptional.

Aged↗

PubMed2002

[Transpupillary thermotherapy for treatment of choroidal melanomas].

PURPOSE: To report the results of transpupillary thermotherapy (TTT) for selected posterior pole choroïdal melanomas. MATERIAL AND METHODS: Prospective study including 56 patients (mean age of 61 years) with choroidal melanoma treated with TTT. All treated tumors had either documented growth or clinical risk factors for future growth and for metastasis. The injection of infracyanine green (I CG) was randomized. RESULTS: The mean initial tumor basal diameter was 7.8 mm and tumor thickness was 3 mm. Twenty-seven tumors (48%) touched the optic disc and sixteen (29%) were under the fovea. Among these 56 patients with choroidal melanoma, 47 patients (84%) presented with primary choroidal melanoma. 9 tumors (16%) were late recurrences after conservative treatment. A mean of three treatment sessions was delivered. After a mean follow-up of 30 months, tumor regrowth was documented in 4 patients (7%) and the visual acuity was the same than the pretreatment acuity in 26 eyes (47%). The mean final thickness was 1.8 mm (percent reduction of tumor thickness was 39%). Intraocular complications included retinal fibrosis and/of retinal striae in 12 eyes (22%) and vascular occlusion in 14 eyes (25%). No statistical impact of ICG administration on the tumor regression was demonstrated. CONCLUSIONS: This series confirms the efficacy of transpupillary thermotherapy in the management of selected posterior pole choroïdal melanomas.

Adult↗

PubMed2001

Emergency hospitalization in the elderly in a French university hospital: medical and social conditions and crisis factors precipitating admissions and outcome at discharge.

Emergency admissions of elderly patients constitute a major management issue due to the complexity of their problems. The aim of this retrospective observational study was to identify medical and social characteristics and crisis factors for emergency department (ED) hospitalization in elderly patients, and to evaluate the influence of these factors on the length of stay and outcome at discharge. During a 4-month period, 396 patients aged 70 years and older were referred to the ED of a University Hospital (Hĵpital Edouard Herriot) in Lyon, France. A questionnaire specifically designed for the study was completed for each patient using the information in the patients' files previously filled in by the "Rapid Geriatric Assessment Team" of the ED. We described civil and marital status, living conditions, reason for admission to ED and other associated pathologies according to the ICM-9, crisis factors, length of stay (LOS) and outcome at discharge. The mean age was 81.9 years (SD 6.5); two thirds (66.7%) of the study subjects were female, and 46.7% were widowed; the majority (68.7%) lived in their own homes. The main reasons for admission were cardiopulmonary diseases in 31.6% of cases, followed by neuropsychiatric disorders in 28.2%, and falls in 8.3%; a final category (31.8%) included subjects admitted for general, non-specific symptoms. Among the crisis factors observed, 49.4% presented an acute episode of a chronic illness, 33.6% lived alone, and 20.9% had been hospitalized during the 6-month period preceding the study. The average LOS was 3.15 days. The multivariate model showed that falls increase LOS by 74%, dementia by 65%, and depression by 21%. Upon discharge, 13% returned to their residence before hospitalization, 55% were transferred to a medical speciality ward, and 4% to other facilities, whereas only 19% were transferred to a geriatric ward, and 9% died during their stay in the ED. The multinomial model showed that outcome at discharge was influenced by functional dependency, dementia, depression, and acute episodes of a chronic illness. For many elderly, the ED remains a critical point of access to more complete managed care. This elderly population is comprised of polypathological, frail persons whose morbid state requires multidisciplinary management in geriatric units. The findings of this study suggest that interventions of multidisciplinary networks, such as home health care programs aimed at detecting crisis factors and establishing early prevention of crisis states, may improve unfavorable medical and social conditions and reduce hospitalization in geriatric patients.

Aged↗

PubMed2000

Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue.

The secretion and the blood levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of the steroid to compensate for the decline counteracts defects associated with aging. The commercial availability of DHEA outside the regular pharmaceutical-medical network in the United States creates a real public health problem that may be resolved only by appropriate long-term clinical trials in elderly men and women. Two hundred and eighty healthy individuals (women and men 60-79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a "young" concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological-clinical manifestations here reported. Bone turnover improved selectively in women >70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create "supermen/women" (doping).

Absorptiometry, Photon↗

PubMed2000

[Characteristics of pain and pain management in the elderly].

A COMMON SYMPTOM: Pain is a common and underestimated problem in older people who are likely to suffer from many acute and chronic conditions. DIFFICULT ASSESSMENT: Clinical assessment of pain often depends on the patient's ability to communicate his or her experience. If self-assessment of pain is not possible, behavioral hetero-evaluation instruments have been built for easy pain assessment by caregivers. ADJUSTED PAIN MANAGEMENT: As for younger patients, the most common strategy for pain management is the use of analgesic drugs. Special care should be taken however when such drugs are initiated in the elderly because increased sensitivity, prolonged drug half-life and adverse effects and drug interactions are more likely.

Aged↗

PubMed2000

Dehydroepiandrosterone replacement administration: pharmacokinetic and pharmacodynamic studies in healthy elderly subjects.

Dehydroepiandrosterone (DHEA; 50 and 25 mg) and placebo tablets were orally administered daily to 24 healthy aging men and women (67.8 +/- 4.3 yr) for 8 days according to a balanced incomplete block design. Nine blood tests on both the first and eighth days allowed the measurement of DHEA, its sulfate DHEAS, and metabolites: testosterone, 5alpha-androstan-3alpha,17beta-diol glucuronide, estradiol, and estrone. Relatively low background levels of DHEA(S) were observed, and with the reestablishment of "young" levels, four important results were obtained. 1) Blood DHEA had an apparent terminal half-life of more than 20 h, the same order of magnitude as that of blood DHEAS, a result explainable by back-hydrolysis of the large amount of DHEAS formed after oral administration of DHEA, a mechanism providing long-lived unconjugated DHEA and metabolites. 2) The metabolic conversion of DHEAS to DHEA was significantly greater in women than in men. 3) No accumulation of steroids was observed. 4) No worrying transformation to androgen and estrogen was recorded; indeed, the limited increased estradiol in aged women could be predicted to be beneficial. These results suggested that daily oral administration of DHEA (25/50 mg) is safe in elderly subjects. The 50-mg dose was chosen for a 1 yr, double blind, placebo-controlled trial of daily oral administration of DHEA in 60- to 80-yr-old individuals (DHEAge).

Aged↗

PubMed1999

Is the LDL receptor-related protein involved in Alzheimer's disease?

LDL-related protein receptor (LRP) is the main receptor in the brain for apolipoprotein E. Moreover, the LRP gene is located on chromosome 12, the site of a potential Alzheimer's disease (AD) locus. We explored the association between the LRP gene and AD in 600 French Caucasian patients (37.8% men, mean age 72.0+/-8.0 years, mean age at onset 68.7+/-8.1 years) and age-matched controls (n=646, 37.0% men, mean age 72.5+/-8.2 years) and observed an association between a (TTTC) repeat at the 3' end of an Alu sequence in the LRP gene and the risk of developing AD. Three alleles were detected in this population [corresponding to 83, 87, and 91 base pairs (bp)], the 91-bp allele being associated with an increased risk of developing AD [all patients: odds ratio (OR) 1.6, P<0.01; late-onset AD: OR 1.8, P<0.01]. This suggests an association between the LRP locus and AD. However, in the light of studies related to the exon 3 LRP polymorphism and given the low strength of the association reported here, a biologically active variant may exist on chromosome 12, either in the LRP gene itself or in another gene in the vicinity.

Age of Onset↗

PubMed1999

Digital necrosis revealing ovarian cancer.

We describe a 57-year-old woman who developed permanent acrocyanosis of all fingers rapidly leading to distal necrosis, revealing an ovarian cancer (OC). Seven similar published cases are reviewed. Digital ischaemia was bilateral, severe and frequently complicated by digital necrosis. OC was of epithelial origin and disseminated at the time of diagnosis. Initial treatment of OC usually resulted in improvement of digital ischaemia. A possible OC should be looked for in women aged 45 years or more presenting with severe digital ischaemia of recent onset.

Adenocarcinoma↗

PubMed1999

The aging process modifies the distensibility of elastic but not muscular arteries.

Aging decreases the distensibility of large elastic arteries; however, the effects of age on the functional parameters of muscular, medium-sized arteries are not well determined. This study evaluated the consequences of aging on the functional parameters of the carotid and radial arteries in normotensive men. A total of 62 elderly subjects (aged 74+/-2 years) were compared with 87 young subjects (aged 35+/-3 years). Internal diameter and intima-media thickness (IMT) were measured by a high-resolution echo-tracking system to calculate distensibility and incremental elastic modulus (Einc). Although in the normal range, systolic and diastolic blood pressure levels were statistically different in the 2 groups at 128+/-19 and 74+/-13 mm Hg versus 121+/-27 and 71+/-18 mm Hg in the young and elderly subjects, respectively (P<0.05). At the carotid artery level, elderly subjects exhibited a greater IMT (742+/-144 versus 469+/-132 microm; P<0.01) and internal diameter (7067+/-828 versus 6062+/-1026 microm; P<0.01) than young subjects; elderly subjects also had lower distensibility (12+/-2 versus 21+/-2 kPa(-1) x 10(-3); P<0.01) and higher Einc (0.9+/-0.2 versus 0.7+/-0.3 kPa x 10(3); P<0.01). At the radial artery level, both IMT (240+/-42 versus 218+/-51 microm; P<0.01) and internal diameter (2685+/-432 versus 2491+/-444 microm; P<0.01) were greater in elderly subjects, but no differences in distensibility and Einc were observed between the 2 groups. All differences remained significant, even after adjusting for mean blood pressure. These results indicate that the increase of the internal diameter and IMT observed during the aging process can have opposite effects on the functional parameters of large elastic or medium-sized muscular arteries.

Adult↗

PubMed1999

[Antihypertensive treatment can normalize the geometry and the arterial function in the aged patient].

The aging process and the elevation of arterial blood pressure (BP) have synergistic effects on the modifications of the arterial system. The effects of the treatment on these modifications are unknown. Our objective was to study the consequences of anti-hypertensive treatment on the geometry and function of the arteries in men over 70 years old. In 89 men aged 74 +/- 2 years, we measured internal diameter and intima-media thickness (IMT) of carotid and radial arteries using high resolution echography (WALL TRACK SYSTEM and NIUS-02), and carotid-femoral pulse wave velocity (PWV) by COMPLIOR. The BP was measured in supine position by Dinamap. In 28 subjects the BP was more than 140/90 mmHg (poor controlled hypertensives-HTpc); in the subjects where BP < 140/90 mmHg, 44 were normotensives (NT) without treatment and 17 were well controlled hypertensives (HTwc) on use of at least one antihypertensive. [table: see text] The PWV was increased in HTpc (20.1 m/s) in comparison with NT (14.6 m/s) and HTwc (16.1 m/s) (p < 0.05). The operational distensibility of radial artery was similar in the three groups. In conclusion, in elderly men aged more than 70 years, the anti-hypertensive treatment can normalize the functional properties and the geometry of muscular and elastic arteries. These results indicate that the arterial modifications observed in elderly hypertensives are consequence of the high blood pressure per se and not only consequent the modifications due to the aging.

Aged↗

PubMed1996

Peripheral antioxidant enzyme activities and selenium in elderly subjects and in dementia of Alzheimer's type--place of the extracellular glutathione peroxidase.

Defenses against free radical damage were determined in red blood cells and plasma from 40 patients with dementia of the Alzheimer-type (DAT) and 34 aged control subjects with normal cognitive function. No crude significant difference in erythrocyte copper-zinc superoxide dismutase (E-CuZnSOD), seleno-dependent glutathione peroxidase (E-GSH-Px), glutathione reductase (E-GSSG-RD) activities, and selenium (Se) concentration was found between DAT cases and control subjects. The peroxidation products evaluated in plasma by the thiobarbituric-reactive material (TBARS) were at the same level in the DAT group as compared to controls. In the DAT group, plasma GSH-Px (P-GSH-Px) activity and plasma Se (P-Se) were negatively correlated with age (r = -0.58; p < 0.001 and r = -0.63; p < 0.001 respectively). Moreover, erythrocyte GSH-Px activity and Se were also negatively correlated with age (r = -0.40; p < 0.01 and r = -0.46; p < 0.01, respectively). No significant correlation with age was observed in the controls. When controlling for age, a significant increase for P-GSH-Px activity and P-Se was observed in DAT patients as compared to controls. These significant differences mostly appeared in DAT subjects under 80 years. Some correlations were only observed in the DAT group such as P-GSH-Px and E-GSH-Px (r = +0.68; p < 0.001); P-GSH-Px and E-Se (r = +0.79; p < 0.001). Correlations between P-GSH-Px and P-Se, E-GSH-Px and P-Se, and P-Se with E-Se are greater in the DAT group (r = +0.84; p < 0.001; r = +0.76; p < 0.001 and r = 0.75; p < 0.001) than in the control group (r = 0.54, pI < 0.01; r = 0.43, p < 0.01 and r = +0.34, p < 0.05 respectively). The fact that first -- a significant increase in P-GSH-Px and P-Se, second -- some modifications in the relationships between antioxidant parameters, and third -- age-dependent decreases of glutathione-peroxidase activities and their cofactor, appeared only in the DAT group suggest that DAT is associated with an oxidative stress due to an imbalance between reactive oxygen species and the peripheral antioxidant opposing forces.

Aged↗

PubMed1995

High-level, stage- and mammary-tissue-specific expression of a caprine kappa-casein-encoding minigene driven by a beta-casein promoter in transgenic mice.

A 5' truncated caprine (ca) kappa-casein-encoding gene (kappa Cas) was fused to the 3' end of a 3' truncated ca beta Cas. The kappa Cas form comprised the 0.8-kb 3' end of intron 2, the remaining part of the transcription unit containing codons -2 to stop 172, and 0.43 kb of the 3' flanking region. The beta Cas form comprised a 3-kb 5' flanking region and the 5' end of the transcription unit terminating 69 bp downstream from exon 2 which encodes the 15-amino-acid (aa) signal peptide and the first 2 aa of mature beta Cas. The resulting hybrid gene driven by the beta Cas promoter was expressed in all eight lines of transgenic mice investigated, although at different levels. In two lines, the yield of recombinant (re-) kappa Cas was > or = 3 mg/ml of milk. The stage- and mammary tissue-specific expression was similar to that of endogenous beta Cas. The re-kappa Cas differed from its goat milk counterpart by the occurrence of four extra aa at the N-terminal end, indicating that the signal peptidase released the beta Cas signal peptide. According to sedimentation analyses of murine milk containing > or = 3 mg re-kappa Cas/ml, the latter essentially occurred in micelles. Preliminary comparative assays of the behavior of ca alpha s1Cas-kappa Cas and alpha s1Cas-re-kappa Cas mixtures upon incremental addition of Ca2+ showed that re-kappa Cas had the capacity to protect alpha s1Cas against Ca(2+)-induced precipitation in forming stable micelles.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1995

Dehydroepiandrosterone sulfate in a long-term care aged population.

Ninety-four institutionalized subjects (mean age 82.9 years; 13 men and 81 women) were assessed for serum dehydroepiandrosterone sulfate (DHEAS) levels. The mean value was 457 ng/ml (SD = 426) in this cross-sectional study. There was a significant decrease in DHEAS levels with age. There was no difference among demented patients with Alzheimer's disease (n = 46), other dementia cases (n = 16), and other individuals (n = 32). The subjects treated for arterial hypertension had significantly lower DHEAS levels. No correlation was found between DHEAS and cortisol values. After age adjustment, no association was observed between DHEAS and chronic diseases, medications, several biochemical or hematological parameters, or 3-year mortality.

Age Factors↗

PubMed1994

Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region.

An association between the 19q13.2 chromosomal region and Alzheimer's disease (AD) has been reported in AD families and for sporadic AD. Recent observations provide evidence that the epsilon 4 allele of the apolipoprotein E gene (APOE), located in this region, is a risk factor for late-onset AD. Within this region, other genes possibly involved in the pathophysiology of AD and in strong linkage disequilibrium with the APOE locus may be responsible for this association. To test this hypothesis, we analysed the allelic distribution of four polymorphic genetic markers flanking the APOE gene (D19S178 (CA)n repeat, D19S47 (CA)n repeat, APOCI HpaI restriction fragment length polymorphism, APOCII (CA)n repeat). We performed these analyses in a sample of late-onset sporadic cases (n = 36) versus controls (n = 38), and in a sample of early-onset sporadic cases (n = 34) versus controls (n = 36). Early-onset cases were analysed for two cut-offs with late-onset: less than 60 and less than 65. We observed a significant increased frequency of the APOE epsilon 4 allele in late-onset and early-onset AD with ages at onset less than 60 and less than 65. The adjusted odds ratio (OR) of the bearers of at least one APOE epsilon 4 allele was 4.10 ([1.84;9.16]) when estimated in both populations with a logistic regression model. Surprisingly, the odds ratio of the bearers of at least one APOE epsilon 2 allele was also significant and equal to 0.11 ([0.02;0.50]) suggesting a possible protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Age of Onset↗

PubMed1994

Serum dehydroepiandrosterone sulfate levels as an individual marker.

To assess the significance of the serum dehydroepiandrosterone sulfate (DHEAS) concentration as a parameter of the individual hormonal milieu, two different groups of subjects were studied: DHEAS levels were determined 3 times at 6-month intervals in 47 elderly hospitalized women, aged 71-94 yr (group 1), and 6 times over 2 consecutive weeks in 10 healthy male volunteers, aged 24-30 yr (group 2). For reference, serum cortisol (F) levels were determined concomitantly. In each group and on each sampling occasion, the subjects were ranked according to their DHEAS or F values. The stability over time of the ranking was much higher for DHEAS than for F; estimated concordance coefficients were 92% (group 1) and 88% (group 2) for DHEAS vs. 51% (group 1) and 49% (group 2) for F. We conclude that due to a comparatively low within- to between-subject variability ratio, DHEAS is a highly specific individual marker.

Adult↗

PubMed1994

Confirmation of the epsilon 4 allele of the apolipoprotein E gene as a risk factor for late-onset Alzheimer's disease.

Family studies indicate a possible linkage between the q13.2 region of chromosome 19 and Alzheimer's disease (AD). An isoform of apolipoprotein E, whose gene maps in this region, is more frequent in AD. In this study, we investigated the possible association of a genetic polymorphism of the apolipoprotein E gene with late-onset AD. We compared apolipoprotein E polymorphism distribution between patients with sporadic late-onset AD (n = 36) and controls of the same age (n = 38). Individuals carrying at least one epsilon 4 allele were present in 41.7% of the patients, compared with only 10.5% of the controls (p < 0.001). This result indicates an association between late-onset AD and the 19q13.2 region containing the apolipoprotein E gene locus.

Age Factors↗

PubMed1994

High lipophilicity decreases drug transport across intestinal epithelial cells.

It is generally admitted in drug research that the passage of molecules across cellular barriers increases with lipophilicity and that the most lipophilic compounds will have the highest intestinal absorption. Using two in vitro models of intestinal epithelium, we presently demonstrate that this concept is not always valid and that highly lipophilic compounds display a low transepithelial permeability. We used epithelial cell lines grown on permeable filters to measure in vitro the transepithelial permeability of various molecules. The octanol/buffer distribution coefficient of the drugs (Do/b) was taken as an index of lipophilicity. When log Do/b values were lower than 3.5, the transepithelial permeability coefficient increased with the lipophilicity. But for log Do/b values ranging from 3.5 to 5.2, the transepithelial permeability coefficient decreased with increasing lipophilicity. Identical results were observed with two differentiated intestinal epithelial cell lines (HT29-18-C1 and Caco-2) and in unstirred or agitated conditions. The results show that an octanol/buffer distribution coefficient value around 3000 corresponds to an optimal transepithelial passage of drugs and that too high a lipophilicity can result in low intestinal epithelial permeability and in low oral absorption.

Biological Transport↗

PubMed1993

HT29-18-C1 intestinal cells: a new model for studying the epithelial transport of drugs.

A polarized differentiated subclone of HT29, a human colon carcinoma cell line, was used to measure the passage of drugs across the intestinal epithelium. These cells, HT29-18-C1, when grown on permeable filters, formed tight monolayers of high electrical resistance (> 400 omega cm2). Electron micrographs revealed the presence of numerous apical microvilli and well developed junctional complexes. The transepithelial passage of various drugs was studied: the transepithelial permeability coefficients ranged from 0.8 x 10(-6) cm/s for fluorescein, to 4.8 x 10(-5) cm/s for the most lipophilic molecule, testosterone. For the five compounds tested, there was a coarse correlation between the apparent transepithelial permeability coefficient and the octanol/buffer distribution coefficient. The HT29-18-C1 subclone thus represents a new in-vitro model for studying the intestinal absorption of drugs.

1-Octanol↗