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Biomedical subjects

M Alt

Publications and source records attributed to M Alt.

At least 19 recordsLinked to original sources
PubMed2006

Memory of childbirth in the second year: the long-term effect of a negative birth experience and its modulation by the perceived intranatal relationship with caregivers.

OBJECTIVE: To assess the memory of various subdimensions of the birth experience in the second year postpartum, and to identify women in the first weeks postpartum at risk of developing a long-term negative memory. DESIGN, METHOD, OUTCOME MEASURES: New mothers' birth experience (BE) was assessed 48-96 hours postpartum (T1) by means of the SIL-Ger and the BBCI (perception of intranatal relationships); early postnatal adjustment (week 3 pp: T1(bis)) was also assessed. Then, four subgroups of women were defined by means of a cluster-analysis, integrating the T1/T1(bis) variables. To evaluate the memory of the BE, the SIL-Ger was again applied in the second year after childbirth (T2). First, the ratings of the SIL-Ger dimensions of T1 were compared to those at T2 in the whole sample. Then, the four subgroups were compared with respect to their ratings of the birth experience at T2 (correlations, ANOVAs and t-tests). RESULTS: In general, fulfillment, emotional adaptation, physical discomfort, and anxiety improve spontaneously over the first year postpartum, whereas in negative emotional experience, control, and time-going-slowly no shift over time is observed. However, women with a negative overall birth experience and a low level of perceived intranatal relationship at T1 run a high risk of retaining a negative memory in all of the seven subdimensions of the birth experience. CONCLUSIONS: Women at risk of developing a negative long-term memory of the BE can be identified at the time of early postpartum, when the overall birth experience and the perceived intranatal relationship are taken into account.

Adolescent↗
PubMed2002

Fatal allergic vasculitis associated with celecoxib.

We report on the occurrence of a rare and as yet unforseeable adverse reaction to treatment with celecoxib, a cyclooxygenase-2 (COX-2) selective, non-steroidal, anti-inflammatory drug. A previously healthy adult suffered fatal acute multiple organ failure presumably after diffuse allergic vasculitis with diffuse necrotic purpura. Although no conclusive proof is available, such a reaction could have been triggered by at least one of two mechanisms: an allergic reaction linked to the chemical structure of celecoxib; or an interaction of the drug with synthesis of endothelial eiconasoids leading to an imbalance between vasoactive end products, resulting in widespread rise to local thrombosis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Clinical and histopathological features of dextran sulfate sodium induced acute and chronic colitis associated with dysplasia in rats.

We examined the clinical and histopathological features of the dextran sulfate sodium (DSS) induced acute and chronic colitis in rats as a model for studying basic biology of the inflamed colonic mucosa. Acute colitis was induced in male Wistar rats by 4 days (AI) or 7 days (AII) of oral 5% (wt/vol) DSS (mol. wt. 54,000) in their drinking water. Chronic colitis was induced in 8 experimental groups: CI=7 days DSS followed by 10 days water (=one cycle); CII=two cycles; CIII to CVIII (three to eight cycles) received only 4 days 5% DSS followed by 10 days drinking water. The entire colons were examined histologically; dysplasia was graded as: indefinite/probably negative for dysplasia, indefinite/probably positive for dysplasia, low-grade dysplasia, or high-grade dysplasia. The earliest clinical findings in the acute colitis group over 4 days occurred on day 2 (hemoccult positive stools, loose stools or diarrhea and weight loss). The maximal disease activity was noted on day 7 accompanied by a 53% mortality rate. The histological inflammation scores were significantly higher on day 7 than on day 4. All rats had extensive ulcerations predominantly in the rectum and cecum. The number of rats having ulcerations was markedly lower in the chronic colitis groups. The majority (75%) of the crypt lesions suspicious for dysplasia were classified as mucosa indefinite/probably negative for dysplasia. We classified 18 crypt lesions as low-grade dysplasia and one lesion as high-grade dysplasia (after eight cycles). No invasive carcinoma was observed. Most low-grade dysplasias (83%) occurred after five cycles of DSS/water, located mostly in the rectum (44%) and colon transversum (33%). Our findings suggest that the DSS colitis model in rats may be an interesting model for studying the sequence chronic inflammation-dysplasia in human ulcerative colitis. Further long-term studies with the present DSS colitis model in rats might also prove it as a reliable model to study the sequence high-grade dysplasia and colitis associated-cancer.

Acute Disease↗
PubMed2000

[Extra-pyramidal syndrome induced by donepezil].

BACKGROUND: The cholinergic hypothesis of Alzheimer's disease is the basis of a new class of drugs: acetylcholinesterase inhibitors. These drugs have few side effects, mainly digestive disorders. CASE REPORTS: Extra-pyramidal side effects with severe gait disorders were observed in 3 patients with Alzheimer's dementia treated with donepezil. This drug was associated with paroxetine or a neuroleptic. In 2 of the 3 cases, the extra-pyramidal effects disappeared when donepezil was discontinued. DISCUSSION: Extra-pyramidal syndromes in elderly subjects with cognitive impairment are difficult to interpret. The possible causes include interactions between acetylcholinesterase inhibitors, neuroleptics and serotonine reuptake inhibitors and Lewy body dementia.

Aged↗
PubMed2000

[The French pharmacovigilance system: structure and missions].

THE NETWORK: The French pharmacovigilance system is composed of a network of 31 regional pharmacovigilance centers located in convenient proximity to health care professionals. CAUSALITY ASSESSMENT: A causality assessment method is compulsory for all persons involved in pharmacovigilance in order to assess the causal relationship between an adverse effect and one or more drugs. PHARMACOEPIDEMIOLOGY: If necessary, an additional evaluation of the causal relationship is performed using pharmacoepidemiology methods. THE NATIONAL COMMISSION: A technical committee and a National Commission of Pharmacovigilance centralizes at the Agence Françiase de Sécurité Sanitaire (or AFSSAPS) and assesses all data in order to provide consensual advise to the relevant authorities on necessary measures, to prevent or reduce a drug-related adverse effect.

Adverse Drug Reaction Reporting Systems↗
PubMed2000

Rapid and reproducible quantification of hepatitis C virus cDNA by fluorescence correlation spectroscopy.

BACKGROUND/AIMS: Standard methods for hepatitis C virus (HCV) RNA quantification are time-consuming and often hampered by low sensitivity. Therefore, we aimed to test whether fluorescence correlation spectroscopy (FCS) could be used to read out HCV polymerase chain reactions (PCR). METHODS: A single-step reverse transcriptase (RT) PCR system was adjusted to the clinically relevant range of 1 x 10(3) to 5 x 10(6) HCV cDNA copies/ml serum. Unpurified amplification mixtures were analyzed by FCS and controlled by HPLC analysis. RESULTS: The outcome of HCV RNA quantitation was nearly identical no matter whether FCS or HPLC techniques were used. FCS-generated standard curves displayed sufficient linearity to allow reproducible determinations. The intraserial variation of cDNA quantification after PCR amplification was +/-3.2%, the interserial variation +/-4.3%. Repeated quantifications of HCV genotype 1b RNA from the sera of 8 patients revealed titers from 1 x 10(4)-5 x 10(6) genome equivalents/ml. The results correlated significantly (r = 0.755; p = 0.03) with a widely used commercially available assay. CONCLUSION: FCS may become a useful tool for rapid and reproducible HCV RNA quantification in the future.

Base Sequence↗
PubMed1999

Novel tetravalent and bispecific IgG-like antibody molecules combining single-chain diabodies with the immunoglobulin gamma1 Fc or CH3 region.

Although bispecific IgG molecules have been successfully applied for antibody-mediated immunotherapy of tumours, applicability is hampered by the difficulties associated with their generation. In the present study, we have used a bispecific single-chain diabody (scDb) directed against carcinoembryonic antigen and Escherichia coli beta-galactosidase as a model to generate bispecific IgG-like antibody molecules. We show that the fusion of this single-chain diabody to the Fc (scDb-Fc) or CH3 (scDb-CH3) region of the human immunoglobulin gamma1 chain results in the expression of dimeric fusion proteins exhibiting four functional antigen binding sites with increased functional affinity. This strategy represents a new and convenient way to generate IgG-like multivalent and bispecific molecules that are efficiently secreted from mammalian cells.

Antibodies, Bispecific↗
PubMed1999

Comparative inhibitory potential of differently modified antisense oligodeoxynucleotides on hepatitis C virus translation.

BACKGROUND: A completely modified phosphorothioate antisense oligodeoxynucleotide (cS-ODN 4) directed against nucleotides 326-348 of the hepatitis C virus (HCV) 5' non-coding region (NCR) efficiently inhibits viral gene expression. As cS-ODN exerts undesired side-effects in vivo, we synthesized partially modified ODN 4 that contained only six modified nucleotides which are located at the ODN termini or are scattered along the molecule. The tested modifications were polar phosphorothioates (S) and non-polar methyl- (M) or benzylphosphonates (B). RESULTS: In an in vitro translation system, specific inhibition of HCV gene expression by M-ODN 4 or B-ODN 4 was observed if terminally modified ODN were used; the maximal inhibition was 92.3% +/- 1.9% and 87.1% +/- 3.7%, respectively, at 10 microgram mol L-1 concentration. S-ODN 4 specifically suppressed viral translation irrespective of the location of the modifications, resulting in a maximal inhibition of 86.3% +/- 3.3%. For all terminally modified ODNs the therapeutic index was high, with tB-ODN 4 the second best at 3.8. Inhibition correlated with efficient RNase H-associated cleavage of target RNA. In transient co-transfection experiments of HepG2 cells with a reporter gene construct and the ODN, terminally modified B-ODN 4 was the most effective and specific inhibitor. At a concentration of 5 microgram mol L-1 the suppression of HCV translation was 96.3% +/- 0.7%. CONCLUSION: These data demonstrate that terminally modified B-ODN 4 is a potent inhibitor of HCV gene expression in vitro and in HepG2 cell culture and may be valuable for future antiviral treatment.

Animals↗
PubMed1997

Core specific antisense phosphorothioate oligodeoxynucleotides as potent and specific inhibitors of hepatitis C viral translation.

Antisense phosphorothioate oligodeoxynucleotides (S-ODN) complementary to sequence stretches in the 5' non coding region (NCR) of the hepatitis C virus (HCV) have recently been shown to effectively inhibit viral gene expression. In order to further delineate the optimum target region in the highly conserved 5' end of the viral RNA, S-ODN complementary to HCV core coding sequences were analysed in the present study. In a rabbit reticulocyte lysate (RRL) in vitro translation assay S-ODN 5, complementary to the HCV-RNA nucleotides 340-353, and S-ODN-6, complementary to nucleotides 348-365, resulted in an inhibition of viral translation of 90.4 +/- 1.3% and 93.7 +/- 5.1%, respectively at a concentration of 4.14 microM. S-ODN 7, complementary to nucleotides 371-388, was relatively inefficient and showed a maximal inhibition of 42.4 +/- 12.2%. It has been suggested that in living cells an inhibition by S-ODN is mainly mediated by the action of RNAse H. In RRL the RNAseH content is very low; therefore, to simulate the situation in living cells inhibition experiments in RRL enriched with RNAse H were performed. Under these conditions S-ODN 5, 6 and 7 inhibited viral translation by 45.6 +/- 6.3%, 80.3 +/- 2.8% and 70.9 +/- 5.7% at concentrations as low as 0.2 microM. At this concentration no inhibition was observed in the standard RRL assay. In cell culture S-ODN 7 was by far the most efficient inhibitor of viral translation, resulting in a specific inhibition of 89.4 +/- 3.6% at a concentration of 0.3 microM. Taken together with the results of our previous study, nucleotides 326-348 comprising the 3' end of the NCR and nucleotides 371-388, located entirely in the core coding region of the HCV RNA, are effective targets for S-ODN mediated inhibition of viral translation.

Animals↗
PubMed1997

Synthetic antisense oligodeoxynucleotides as potential drugs against hepatitis C.

Antisense oligodeoxynucleotides (ODNS) can be used to specifically inhibit hepatitis C viral gene expression. Due to its high degree of conservation and its important function as internal ribosomal entry site, the 5'-non-coding region of the hepatitis C virus has been the most effective target to inhibit translation so far. Inhibition of luciferase reporter gene expression of up to 96 +/- 2% has been achieved. Modifications of ODNs like phosphorothioate, methylphosphonate or benzylphosphonate modification of terminal or intramolecular internucleotide phosphates lead to altered lipophilicity and binding stability to its RNA target and resistance against serum nucleases. The mode of action of ODNs is mainly dependent on an efficient induction of RNase H activity. The uptake of ODNs occurs via receptor-mediated or absorptive and fluid-phase endocytosis. After release from the endosomes, ODNs may exert their effects by interaction with cytosolic or nuclear structures. Side effects can occur when this interaction affects intra- or extracellular targets essential for biological cell function. If these problems can be solved, antisense technology has the potential for future therapy of human disease.

Antiviral Agents↗
PubMed1996

Hepatitis C virus infection as a major risk factor for hepatocellular carcinoma.

Evidence of a tumorigenic potential of the hepatitis C virus (HCV) has so far come mainly from epidemiological data. Longitudinal studies have shown that 16 of 62 anti-HCV antibody (ab)-positive Japanese patients developed hepatocellular carcinoma (HCC) within 5 yr. HCC-related deaths were significantly (p = 0.01) higher in Swedish anti-HCV ab-positive patients than in anti-HCV ab-negative controls (18 vs. 4%). The relative frequency of anti-HCV ab in HCC patients has been reported to be as high as 72% in Spain, 49-62% in Italy and 58% in France. It ranges between 9 and 36% in the USA and is about 26% in Germany. In HBV-endemic areas like South East Asia and Equatorial Africa, HCV-related HCCs play a minor role. The relative risk of developing HCC was elevated (up to 69.1-fold) for anti-HCV ab-positive patients as compared to anti-HCV ab-negative controls in almost all geographic areas studied to date. There is some evidence for an increased risk of developing HCC when hepatitis B virus (HBV) coinfection is present. Cirrhosis is likely to represent an additional risk factor for the development of HCC in anti-HCV ab-positive patients. Blood transfusions are the source of infection in barely one third of anti-HCV ab-positive HCC patients. There seems to be no significant difference in age or gender between anti-HCV ab-positive and ab-negative HCC patients. The additional impact of alcohol consumption and of the HCV genotype is presently under investigation. On the molecular level, HCV replication intermediates have been detected in HCC tissue and point mutations within the p53 gene have been demonstrated. However, the pathomechanism leading to HCV-mediated cell transformation remains unsolved.

Carcinoma, Hepatocellular↗
PubMed1995

Colonization of Transgenic Tobacco Constitutively Expressing Pathogenesis-Related Proteins by the Vesicular-Arbuscular Mycorrhizal Fungus Glomus mosseae.

We studied the effect of constitutive expression of pathogenesis-related proteins (PRs) in tobacco plants on vesicular-arbuscular mycorrhiza. Tobacco lines genetically transformed to express various PRs constitutively under the control of the cauliflower mosaic virus 35S promoter of tobacco were examined. Immunoblot analysis and activity measurements demonstrated high levels of expression of the PRs in the root systems of the plants. Constitutive expression of the following acidic isoforms of tobacco PRs did not affect the time course or the final level of colonization by the vesicular-arbuscular mycorrhizal fungus Glomus mosseae: PR-1a, PR-3 (=PR-Q), PR-Q(prm1), PR-4, and PR-5. Similarly, constitutive expression of an acidic cucumber chitinase, of a basic tobacco chitinase with and without its vacuolar targeting peptide, of a basic (beta)-1,3-glucanase, and of combinations of PR-Q and PR-Q(prm1) or basic chitinase and basic (beta)-1,3-glucanase did not affect colonization by the mycorrhizal fungus. A delay of colonization by G. mosseae was observed in tobacco plants constitutively expressing the acidic isoform of tobacco PR-2, a protein with (beta)-1,3-glucanase activity.

Journal Article↗