PubMed Health⌕ Search

Biomedical subjects

P Colin

Publications and source records attributed to P Colin.

106 records · Page 6Linked to original sources
PubMedDate not supplied

Controlled transgene expression by E1-E4-defective adenovirus vectors harbouring a "tet-on" switch system.

BACKGROUND: The "tet switch system" was originally described under the tet-off configuration with its components encoded by two separate plasmids. Since then, many virus vectors harbouring tet-off components have been designed and their regulation by tetracycline is widely reported. On the contrary, tet-on regulation by viral vectors is poorly documented. METHODS: E1-E4-defective adenoviruses harbouring either rtTA or the luciferase gene under a minimal inducible promoter (TK* or CMV*) or both components in a single genome were produced. Using either a double or a single virus strategy, induction of luciferase expression was investigated in various cell lines, in mice muscle and in rat brain. RESULTS: Over 400-fold induction can be reached with PC12 and NHA cells using a double virus strategy. Comparison of the background activity of different minimal inducible promoters revealed a significant difference between TK* and CMV* promoters both with the cell culture and the in vivo experiments. Interestingly, a single virus strategy permitted an induction exceeding 600-fold with human astrocyte primary cells. Moreover, the E1-E4-defective adenovirus-mediated tet-on system can be quickly switched off and turned back on again. Depending on the cell line, the level of rtTA derived by the single virus strategy differed, resulting in different efficiencies. Experiments performed in rat striatum and mouse muscle confirmed the importance of rtTA expression and minimal promoter used on both doxycycline-independent expression and induction efficiency. Under appropriated rtTA expression, a 32-fold induction is observed in mouse muscle. CONCLUSIONS: In the recombinant adenovirus context, the CMV* but not the TK* promoter is sensitive to transcriptional interference resulting in high doxycycline-independent expression. By paying attention to the rtTA expression, moderate and high induction can be obtained in vivo and in vitro accordingly.

Adenoviridae↗
PubMedDate not supplied

Spermicidal activity of a new contraceptive sponge.

An open, crossover study evaluated the spermicidal efficacy and irritative potential of the Protectaid sponge. Postcoital tests were conducted in nine healthy couples under control conditions (no sponge) and with the sponge. Microscopic examination of postcoital mucus from the female partners showed that sperm entered the cervix in all nine controls, whereas entry was completely prevented by the sponge in four of nine women. None of the participants showed colposcopic evidence of mucosal irritation while using the sponge. Colposcopic abnormalities were evident in two of nine women during control testing. The urgent need for female-controlled contraceptive methods with the potential to protect against sexually transmitted diseases makes this low-dose spermicidal vaginal sponge an effective and safe alternative.

Adolescent↗
PubMedDate not supplied

[Fractionated stereotactic radiotherapy: results in hypophyseal adenomas, acoustic neurinomas, and meningiomas of the cavernous sinus].

PURPOSE: In order to optimize cerebral benign tumor irradiation, fractionated stereotactic radiotherapy allows a focused-volume irradiation (2.1 cm3, 16 mm diameter) under standard fractionation conditions. Results of a retrospective and multicentric analysis are presented. PATIENTS AND METHODS: Fractionated stereotactic radiotherapy uses the ballistic principles of the radiosurgery: stereotactic localization, multi-beam irradiation, secondary collimation, three-dimensional dosimetry. Standard fractionation is possible with a re-locatable non-invasive stereotactic device. The technique has been used for treating pituitary adenomas (86 patients), acoustic neuromas (32 patients) and cavernous meningiomas (26 patients). RESULTS: 1) pituitary adenomas: cumulative tumoral objective-response rates (42 patients) were respectively 42%, 69% and 88% at 24, 48 and 60 months. The cumulative endocrinologic objective-response rates (32 patients) were respectively 53%, 75% and 85% at 24, 48 and 60 months. The cumulative risk of radio-induced hormonal deficiency varied from 18% (growth hormone [GH]) to 42% for TSH (thyroid stimulating hormone) at 48 months. No other complication was observed; 2) acoustic neuromas: 33 tumors, < 25 mm in diameter, were treated in 32 patients. Tumor control was observed in 29/33 tumors: 14 were stable, 15 decreased and three progressed. Useful hearing was maintained in 9/10 patients. Only three patients (9%) presented persistent complications; 3) cavernous meningioma: 17/19 clinical responses were noted, 20 tumoral stabilisations, one partial response and one progression (22 magnetic resonance imaging [MRI] evaluable patients). One unilateral radio-induced blindness was observed. CONCLUSION: For these benign tumors, the focused target volume obtained by the fractionated stereotactic radiotherapy seems to be better adapted to the treatment of limited benign tumors than standard radiotherapy. The use of standard fractionation reduces the risk of severe normal tissue damage, sometimes observed for radiosurgery and inherent in the use of single fraction.

Adenoma↗
PubMedDate not supplied

Bismuth-based triple therapy with bismuth subcitrate, metronidazole and tetracycline in the eradication of Helicobacter pylori: a randomized, placebo controlled, double-blind study.

OBJECTIVE: To determine the rate of Helicobacter pylori eradication following bismuth-based triple therapy with colloidal bismuth subcitrate, tetracycline hydrochloride and metronidazole. PATIENTS AND METHODS: One hundred and eleven patients were randomly assigned, in a two to one ratio, to colloidal bismuth subcitrate 120 mg qid plus metronidazole 250 mg qid plus tetracycline 500 mg qid (Gastrostat), or matching placebo tablets and capsules for 14 days. Presence or absence of H pylori was documented by histology at entry and at least 28 days after treatment. Patients had dyspeptic symptoms with or without a history of peptic ulcer. Patients with any previous attempt(s) at eradication of H pylori, who used bismuth, antibiotics, H2 receptor antagonists or proton pump inhibitors in the previous four weeks were excluded. RESULTS: Fifty-three of 59 (90%) patients on bismuth-based treatment and only one of 35 (3%) on placebo achieved eradication by per protocol analysis. Fifty-three of 65 (82%) patients on bismuth-based treatment achieved eradication, while only two of 34 (5%) achieved eradication on placebo by intention to treat analysis. Eradication rates for bismuth-based treatment across sites ranged from 83% to 100%. Only two patients in the bismuth-based treatment group (4%) and one in the placebo group (3%) discontinued treatment because of adverse events. CONCLUSIONS: Colloidal bismuth subcitrate plus metronidazole plus tetracycline, given in the doses studied for 14 days, is safe and highly effective against H pylori infection and would be appropriate as a first-line therapy for eradication.

Adolescent↗
PubMedDate not supplied

[Therapeutic perspectives in the treatment of stable angina].

Five groups of drugs are presently available to reduce the symptoms associated with angina pectoris: beta-blockers, calcium channel antagonists, nitrates, potassium channel agonists and trimetazidine. beta-blockers remain the drugs of first strategy since they are unique in reducing major cardiac events. Angiogenesis and gene therapy are still in the field of research. The second therapeutic goal is to reduce cardiovascular morbi-mortality. Inhibitors of platelet aggregation, hypolipemic agents and converting enzyme inhibitors have proved their efficacy in these fields. Conversely, vitamins C, E and B, antibiotics against intra-cellular germs and substitutive hormonotherapy of post-menopausal women must yet prove their efficacy.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Evaluation of two dose individualisation methods for carboplatin.

The pharmacokinetics of carboplatin are usually evaluated by measuring plasma concentrations of ultrafiltered platinum (UP). This approach, however may be less reliable than measuring the plasma concentration of total platinum (TP). In a group of 14 patients, which constituted a reference group, the clearance of TP was highly correlated with creatinine clearance, as estimated by the method of Cockroft and Gault. This relationship, together with only morphological and biological parameters, was used to estimate TP clearance, Vc and AUC, in a validation group of 8 patients. Estimated TP clearance was 97.9 +/- 18% of the actual value. The TP pharmacokinetic parameters of the reference group were used to estimate those of the validation group, using only two or three plasma concentration measurements (Bayesian approach). With the Bayesian approach, the estimated TP clearance was up to 99.9 +/- 2.7% of the actual value. In conclusion, estimation of TP pharmacokinetics may be reliably estimated as an alternative to UP in clinical practice.

Adult↗
PubMedDate not supplied

Variability in the resistance of four chicken lines to experimental intravenous infection with Salmonella enteritidis phage type 4.

The capacity of four chicken lines (Y11, L2, B13, PA12) to control Salmonella enteritidis (SE) phage type 4 (PT4) systemic colonization was investigated. Thirteen-week-old chickens were intravenously inoculated with 10(6) SE colony-forming units, and the levels of SE colonization were determined at various time intervals after inoculation in liver, spleen, genital organs, and ceca. The course of SE infection showed a rapid contamination of liver, spleen, and genital organs, whereas the ceca were infected later. A significant (P < 0.001) effect of the chicken line on levels of SE was detected on day 3 postinoculation (PI) in liver and ceca, on day 10 PI in ceca, and on day 15 PI in spleen. Because an early control of systemic Salmonella infection by the Ity/Nramp1 gene has been demonstrated in mice, we aimed to study the early resistance of chickens to SE. As a consequence, we then focused our study on the between- and within-line variabilities of SE levels on day 3 PI. According to the SE levels in liver on day 3 PI, the chicken lines could be classified as susceptible (Y11 and L2) or resistant (PA12 and B13). This early variability was explored in resistant B13 and susceptible L2 lines. Differences between these two lines were confirmed in liver but not in ceca. A large within-line variability was observed in all organs of these two lines. The genetic origin of this variability will have to be determined as a prerequisite to an eventual selection.

Animals↗