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Biomedical subjects

P Dumont

Publications and source records attributed to P Dumont.

At least 19 recordsLinked to original sources

The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth.

The incidence of prostate cancer is increasing in western countries because of population aging. Prostate cancer begins as an androgen-dependent disease, but it can become androgen independent at a later stage or in tumors recurring after an antihormonal treatment. Although many genetic events have been described to be involved in androgen-dependent and/or -independent prostate cancer growth, little is known about the contribution of epigenetic events. Here we have examined the possibility that the methyl-CpG-binding protein MECP2 might play a role in controlling the growth of prostate cancer cells. Inhibition of MECP2 expression by stable short hairpin RNA stopped the growth of both normal and cancer human prostate cells. In addition, ectopic expression of the MECP2 conferred a growth advantage to human prostate cancer cells. More importantly, this expression allowed androgen-dependent cells to grow independently of androgen stimulation and to retain tumorigenic properties in androgen-depleted conditions. Analysis of signaling pathways showed that this effect is independent of androgen receptor signaling. Instead, MECP2 appears to act by maintaining a constant c-myc level during antihormonal treatment. We further show that MECP2-expressing cells possess a functional p53 pathway and are still responsive to chemotherapeutic drugs.

Androgens↗

Contraceptive counselling and social representations: a qualitative study.

BACKGROUND: Contraceptive use is a complex issue and several studies have been conducted in an effort to understand user behaviour. It is of interest to explore the representations of professionals who give advice on contraception, since their views could have an impact on contraceptive use. METHODS: Individual in-depth interviews of 65 healthcare professionals likely to provide contraceptive advice to patients at a Swiss maternity unit. RESULTS: 83% of healthcare professionals interviewed were favourable to contraception in general while being highly critical of its practical efficacy. The methods most often spontaneously cited were oral contraceptive pills, male condom, intrauterine devices and hormonal implants. Theoretically, all methods should be proposed during contraceptive counselling but in practice interviewees have different social representations of user groups and associate them with specific contraceptive methods. Personal experience appears to play a bigger role than scientific knowledge. CONCLUSIONS: The counsellor's social representations probably play an important role in determining user behaviour. These representations should be taken into consideration in the training of healthcare professionals in this field.

Adult↗

[Quick detection of depression: a significant clinical issue].

Detection of depression is a major issue for public health. In a study performed in the HUG, we tested the concordance of the self-report Patient Health Questionnaire (PHQ-9) with the Hamilton depression scale (HDRS) administered by a psychiatrist, as measures of the severity of depression. The comparison shows that the PHQ-9 distinguishes subjects with and without depressive disorders and is a good screener for severe disorders but has a poor capacity of discrimination when disorders are mild. This instrument is insufficient if the aim is to detect mild or moderate depressive disorders, wich is the most frequent occurrence in patients consulting primary care physicians.

Depression↗

Efficacy and safety of imidacloprid 10% plus moxidectin 2.5% spot-on in the treatment of sarcoptic mange and otoacariosis in dogs: results af a European field study.

Efficacy and safety of treatment with imidacloprid 10%+moxidectin 2.5% spot-on (Advocate, Advantage multi; Bayer AG, Leverkusen, Germany) were tested in dogs naturally infested with Sarcoptes scabiei or Otodectes cynotis in a multi-centre, controlled, randomized, blinded field study conducted in France, Germany, Albania and the UK. The study was performed according to a non-inferiority design to demonstrate that the efficacy of imidacloprid/moxidectin spot-on was not inferior to that of a control product containing selamectin (Stronghold spot-on; Pfizer). All Sarcoptes-infested dogs were topically treated twice (days 0 and 28) with the dosage recommended by the respective manufacturer (27 dogs with imidacloprid/moxidectin, 26 with selamectin). All Otodectes-infested dogs were treated on day 0 (35 dogs with imidacloprid/moxidectin, 34 with selamectin), and only those still positive on day 28 received a second treatment. Parasitological cure rate in Sarcoptes-infested dogs was 100% for both treatments, while parasitological cures rates in the Otodectes-infested dogs at day 28 and day 56 were 68.6 and 85.7% with imidacloprid/moxidectin, and 64.7 and 88.2% with Stronghold. Non-inferiority of Advocate was confirmed statistically. Clinical assessment of skin lesion scores at day 56 showed that with either product >96% of the dogs treated against sarcoptic mange were improved or cured, the difference between the groups being non-significant. On the basis of a final clinical assessment of lesion scores, 80% of the dogs treated with imidacloprid/moxidectin against otoacariosis and 85.3% of those treated with selamectin were rated cured or improved. Only three mild, possibly drug-related adverse reactions were observed among alI treated animals (two in the imidacloprid/moxidectin group, one in the selamectin group). It is concluded that imidacloprid/moxidectin spot-on is an effective and safe treatment for sarcoptic mange and otoacariosis in the dog.

Administration, Topical↗

Evaluation of the efficacy and safety of imidacloprid 10% plus moxidectin 2.5% spot-on in the treatment of generalized demodicosis in dogs: results of a European field study.

Efficacy and safety of the test product imidacloprid 10%+moxidectin 2.5% spot on (Advocate, Advantage multi) in the treatment of canine generalized demodicosis were evaluated in a multi-centre, controlled, randomized, blinded field study in Albania, France, and Germany. The study was conducted according to a non-inferiority design to demonstrate that the efficacy of the test product is not inferior to that of a control product containing milbemycin oxime (Interceptor, tablets for oral application). Of the 72 dogs enrolled, all of which expressed clinical signs of generalized demodicosis, 63 completed the study. Of these, 30 dogs were treated 2-4 times, at 4-week intervals, with the test product at the recommended dose of at least 0.1 ml/kg body weight. Thirty-three dogs were treated daily for two to four periods of 4 weeks with the control product according to label instructions (0.5-1 or 1-2 mg/kg body weight). Presence of mites in deep skin scrapings and clinical improvement were assessed 3-6 times at each inspection at 4-week intervals. Treatment was discontinued in dogs negative for mites on two subsequent examinations 4 weeks apart or at the last examination on day 84. At the end of the trial, dogs in both groups showed a similar clinical improvement. No Demodex mites were detected in 26 of 30 dogs treated with imidacloprid/moxidectin and in 29 of 33 dogs treated with milbemycin oxime. Statistical evaluation confirmed that the efficacy of the test product in the treatment of generalized canine demodicosis was not inferior to that of milbemycin oxime.

Administration, Topical↗

[Paraneoplastic pemphigus revealing dendritic cell sarcoma originating from Castleman's disease of the neck].

INTRODUCTION: Paraneoplastic pemphigus is associated with Castleman's disease. We report a case of paraneoplastic pemphigus at the stage of the sarcomatous transformation of Castleman's disease, present for many years but without concomitant paraneoplastic pemphigus. The pemphigus was manifested by the most unusual, exclusive, involvement of the mucosa of the mouth and lung. OBSERVATION: A 32 year-old man suffering from extensive ulceration of the oral mucosa was hospitalized in December 2000 for alteration in his general status of health and acute respiratory failure. The search for intercellular anti-substance antibodies on rat spleen was positive, corresponding to anti-envoplakin IgG and leading to the diagnosis of paraneoplastic pemphigus. The thoracic x-ray and scan revealed a hilum tumor, the histological examination of which confirmed the diagnosis of Castleman's disease concomitant to sarcomatous transformation. Following surgical treatment, the respiratory failure worsened. The patient improved with systemic corticosteroids at the dose of 2 mg/kg/d and chemotherapy was initiated. The patient died suddenly within the context of acute respiratory failure, three months after surgery. DISCUSSION: This is a case of paraneoplastic pemphigus of unusual clinical and biological expression: exclusively mucosal involvement with obliterating bronchiolitis, explained by the isolated presence of antibodies recognizing envoplakin, without anti-desmoglein. The transformation of the Castleman tumor into a sarcoma may have unmasked intra-cellular antigens (plakins), initiating the specific immune reaction.

Adrenal Cortex Hormones↗

[Lympho-epithelial thymoma revealed by a cardiac tamponade].

The authors report the case of a 62 year old patient admitted for a tamponade, revealing a mixed lympho-epithelial thymoma with invasion of the pericardium, the aorta and of the pulmonary arteria. The histological diagnosis was confirmed by a surgical biopsy performed after emergency pericardiocentesis. A neoadjuvant chemotherapy was administered followed by incomplete surgical resection and then a post operative radiotherapy. A local relapse was diagnosed at one year follow up by CT scan and a second line chemotherapy was administered. No further relapse occurred and patient was alive at four years.

Cardiac Tamponade↗

Growth kinetics rather than stress accelerate telomere shortening in cultures of human diploid fibroblasts in oxidative stress-induced premature senescence.

WI-38 human diploid fibroblasts underwent accelerated telomere shortening (490 bp/stress) and growth arrest after exposure to four subcytotoxic 100 microM tert-butylhydroperoxide (t-BHP) stresses, with a stress at every two population doublings (PD). After subcytotoxic 160 microM H2O2 stress or five repeated 30 microM t-BHP stresses along the same PD, respectively a 322 +/- 55 and 380 +/- 129 bp telomere shortening was observed only during the first PD after stress. The percentage of cells resuming proliferation after stress suggests this telomere shortening is due to the number of cell divisions accomplished to reach confluence during the first PD after stress.

Cell Division↗

Benign mediastinal lymphadenopathy in congestive heart failure.

We report three cases of benign mediastinal lymphadenopathy revealed by chest radiography in patients ranging in age from 61 to 75 years. All three patients had severe coronary heart disease and a history of several episodes of acute cardiac decompensation. Chest CT scanning contributed to the diagnosis by revealing the existence of multiple enlarged lymph nodes, mostly 10 to 17 mm in short-axis diameter. CT scanning also confirmed the disappearance of the mediastinal lymph nodes in one patient on follow-up after treatment with diuretics and digitalis. Histopathology investigations of biopsy samples obtained by mediastinoscopy consistently revealed noninflammatory, benign lesions that did not affect the node structure. Our report draws attention to the particular nosology of left heart disease represented by benign enlarged lymph nodes of the mediastinum and pulmonary edema. The diagnostic approach to such lymphadenopathy should be guided by the radiologic regression seen on follow-up CT scanning while the patient was undergoing appropriate therapy for congestive heart failure, which constitutes a decisive argument for the congestive heart failure origin.

Aged↗

[Treatment of traumatic corneal abrasion with contact lens associated with topical nonsteroid anti-inflammatory agent (NSAID) and antibiotic: a safe, effective and comfortable solution].

PURPOSE: To evaluate the benefit of using therapeutic soft contact lenses in association with NSAID and antibiotic drops for the treatment of traumatic corneal abrasions. The impact on patient pain and on the incapacity to work are analyzed. METHODS: The treatment of 176 consecutive patients presenting with traumatic corneal abrasion was evaluated in a prospective study. Therapeutic contact lenses, NSAID drops (diclofenac), and antibiotic drops (tobramycin) without cycloplegia were used. RESULTS: Psychometric evaluation of pain revealed sufficient comfort with this regimen, allowing 123 patients (80.39%) to immediately go back to their occupations. This return to usual occupations varied with the size of the abrasion: it was obtained in 80 patients (93.02%) from the "foreign body" group (size of abrasion < 10 mm2). In the "other etiologie" group, this ability was obtained in 30 of 41 patients (73.17%) presenting an abrasion smaller than 10 mm2, in 6 of 13 patients (46.15%) presenting an abrasion between 10 and 20 mm2, and in 7 of 9 patients (77.78%) presenting an abrasion between 20 and 30 mm2. All the patients with an abrasion longer than 30 mm2 were unable to continue usual occupations. No serious complications appeared during treatment. CONCLUSION: Treatment of traumatic corneal abrasion with a contact lens associated with topical NSAID drops sufficiently reduced the pain to allow 80.39% of the patients to go return immediately to their normal activities. The combined use of soft contact lenses, NSAID drops, and antibiotic drops without cycloplegia appeared to be an effective treatment for traumatic corneal abrasion.

Adolescent↗

Inpatient opiate detoxification in Geneva: follow-up at 1 and 6 months.

The aim of this study was to identify predictors of treatment success and of relapse, 1 and 6 months after inpatient opiate detoxification in an 8-bed unit in Geneva. Of all 73 patients admitted between June 1994 and June 1995, a majority (73%) successfully finished opiate detoxification. Detoxification was performed mainly with methadone tapering; the average duration of hospitalisation was 15 days. Factors associated with treatment failure were: cocaine abuse, presence of legal problems, and short duration of hospital stay. After 1 month, 65% of the patients were using drugs (half of them were dependent again, half of them had used occasionally) and 35% were completely abstinent (21% when excluding those in residential treatment). Predictors of rapid relapse were cocaine abuse and little concern with own psychological situation at baseline. After 6 months, 50% were physically dependent again, 13% had lapsed occasionally, 37% were abstinent (28% when excluding those in residential treatment). Only high benzodiazepine use at baseline was associated with medium term abstinence. Addiction severity index composite scores had considerably improved between baseline and 6 months. Prevention of relapse to opiate use after inpatient detoxification, especially for those with a concurrent cocaine abuse, should be improved.

Adolescent↗

Induction of replicative senescence biomarkers by sublethal oxidative stresses in normal human fibroblast.

We tested the long-term effects of sublethal oxidative stresses on replicative senescence. WI-38 human diploid fibroblasts (HDFs) at early cumulative population doublings (CPDs) were exposed to five stresses with 30 microM tert-butylhydroperoxide (t-BHP). After at least 2 d of recovery, the cells developed biomarkers of replicative senescence: loss of replicative potential, increase in senescence-associated beta-galactosidase activity, overexpression of p21(Waf-1/SDI-1/Cip1), and inability to hyperphosphorylate pRb. The level of mRNAs overexpressed in senescent WI-38 or IMR-90 HDFs increased after five stresses with 30 microM t-BHP or a single stress under 450 microM H(2)O(2). These corresponding genes include fibronectin, osteonectin, alpha1(I)-procollagen, apolipoprotein J, SM22, SS9, and GTP-alpha binding protein. The common 4977 bp mitochondrial DNA deletion was detected in WI-38 HDFs at late CPDs and at early CPDs after t-BHP stresses. In conclusion, sublethal oxidative stresses lead HDFs to a state close to replicative senescence.

Biomarkers↗

Exposure of Chironomus riparius larvae (diptera) to lead, mercury and beta-sitosterol: effects on mouthpart deformation and moulting.

Mouthpart deformation in chironomid larvae is induced by exposure to chemical contaminants and is becoming an established bio-indicator in sediment assessment programmes. However, concentration-response relationships with causal agents have only been established occasionally and with varying success. In this laboratory study, instar II and III larvae were exposed to sub-lethal concentrations of lead, mercury and beta-sitosterol. A significant deformation response was induced in the pecten with lead and mercury. Deformation frequencies of the mentum after metal exposures were not significantly different from the control. Moulting was retarded by both metals and was well correlated with mouthpart deformation. The beta-sitosterol is an endocrine disruptor, which was used to test the hypothetical cause-effect relation between disruption of ecdyson functioning and chironomid deformation. In the present study, exposure to sublethal concentrations of beta-sitosterol did not result in any effect on deformation or moulting. As such, the proposed hypothesis of endocrine disruptors as primary causal agents of chironomid deformation could not be substantiated. Acetone, which was used as a solvent to apply beta-sitosterol caused a significant increase of mentum deformation. The ground filtration paper used as substrate seemed to induce deformities as well. Substrate contamination, acetone and (especially) inbreeding were most probably responsible for the high deformation frequencies in the control conditions.

Animals↗

Stress-induced premature senescence as alternative toxicological method for testing the long-term effects of molecules under development in the industry.

No alternative in vitro method exists for detecting the potential long-term genotoxic effects of molecules at subcytotoxic concentrations, in terms of days and weeks after exposure(s) to the molecule tested. A theoretical model of cellular senescence led to the concept that subcytotoxic stresses under any molecules at subcytotoxic doses, such as molecules under development in the pharmaceutical, cosmetics and food industry, might lead human fibroblasts into a state closely related to in vitro senescence. This concept was then experimentally confirmed in vitro: many biomarkers of replicative senescence of human fibroblasts were found 72 h after their exposure to various kinds of stressors used at non-cytotoxic concentrations. This phenomenon has been termed stress-induced premature senescence (SIPS). Moreover, proteomics studies have revealed that, besides their effects on the appearance of the biomarkers of senescence, sublethal stresses under a variety of stressors also lead to long-term specific changes in the expression level of proteins which are stress-specific. These changes have been coined the molecular scars of stress. The proteins corresponding to these molecular scars may be identified using the latest developments in mass spectrometry. This model of stress-induced premature senescence may be applied to the toxicological sciences when testing for the potential irreversible long-term effects of molecules on the cell fate.

Aging, Premature↗

Appearance of biomarkers of in vitro ageing after successive stimulation of WI-38 fibroblasts with IL-1alpha and TNF-alpha: senescence associated beta-galactosidase activity and morphotype transition.

Sublethal oxidative stresses increase the proportions of human fibroblasts positive for senescence associated beta-galactosidase activity and accelerate the transition in the fibroblast morphotypes characterising fibroblast ageing. Stimulation of fibroblasts with TNF-alpha or IL-1alpha transiently increases the production of reactive oxygen species (ROS) in human fibroblasts. Here we propose that repeated stimulation of WI-38 fibroblasts with TNF-alpha or IL-1alpha can generate enough ROS to accelerate the transition in the fibroblast morphotypes and increase the proportion of cells positive for senescence associated beta-galactosidase activity. The involvement of ROS is suggested by experiments where the stimulation of fibroblasts with TNF-alpha or IL-1alpha are performed in the presence of N-acetylcysteine which increases the intracellular antioxidant potential. It is proposed that the decrease in the proportions of morphotypes I and II, and the increase in the proportions of morphotypes III to VI observed after successive stimulation with TNF-alpha or IL1-alpha is attributed to an increased ROS production occurring during the stimulation.

Acetylcysteine↗