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Biomedical subjects

M Gaillard

Publications and source records attributed to M Gaillard.

At least 19 recordsLinked to original sources

[A crisis team in the field of old age psychiatry].

In the context of demographic evolution, psychiatric care needs increase steadily in most western countries. Given the financial limitations, it is mandatory to establish appropriate care priorities in order to avoid psychiatric hospitalisations by assisting care providers, general practionners and nurses, at home or in the nursing homes. A crisis team has been established 18 months ago within the Division of old age psychiatry in Lausanne. The care program included immediate assistance in the community, assessement, crisis counseling, medication consultation and referral for psychiatric services providing an alternative to hospitalization. The first results indicate that this intervention is well accepted by the users and correspond to a real need.

Aged↗

A new selective estrogen receptor modulator HMR-3339 fully corrects bone alterations induced by ovariectomy in adult rats.

The selective estrogen receptor modulator (SERM) raloxifene has been shown to reduce the risk of vertebral fracture, but without significant effect on nonvertebral fractures. However, there is a need for SERMs capable of improving mechanical competence and reducing the risk of fractures at multiple skeletal sites, with minimal side effects. We investigated the effects of a new steroidal SERM, HMR-3339, compared to raloxifene, on bone strength and its determinants (BMD, microarchitecture, dimensions) at various skeletal sites (lumbar spine, tibia, and femur) of adult ovariectomized rats in both prevention and intervention protocols. In a prevention study, HMR-3339 and raloxifene treatments fully prevented alterations of bone strength. In an intervention protocol, where treatment was started 8 weeks after ovariectomy, HMR-3339 fully restored mechanical properties by influencing both areal BMD and outer diameter. This effect was observed at skeletal sites formed of cancellous and cortical bone or of cortical bone only. In contrast, raloxifene positively influenced structures containing mainly cancellous bone. In HMR-3339-treated rats, IGF-I plasma levels were higher than in ovariectomized controls; this was not observed with raloxifene. In conclusion, these results indicate that HMR-3339 increased not only bone mineral mass, but also restored bone mechanical strength at multiple sites in adult osteoporotic rats. In contrast to raloxifene, HMR-3339 also influenced skeletal sites predominantly formed of cortical bone.

Animals↗

Genetic elements of Thermococcales.

This minireview summarizes our current knowledge about archaeal genetic elements in the hyperthermophilic order Thermococcales in the phylum Euryarchaeota. This includes recent work on the first virus of Pyrococcus, PAV1, the discovery of novel unique virus morphotypes in hot deep-sea environments, and preliminary observations on novel cryptic plasmids. We also review the work accomplished over the last 5 years in the development of genetic tools for members of the Pyrococcus and Thermococcus genera, mainly in our laboratories.

Antigens, Archaeal↗

PAV1, the first virus-like particle isolated from a hyperthermophilic euryarchaeote, "Pyrococcus abyssi".

We describe the first virus-like particle of a hyperthermophilic euryarchaeote which was discovered in a strain of "Pyrococcus abyssi" previously characterized in our laboratory. This particle, named PAV1, is lemon-shaped (120 nm x 80 nm), with a short tail terminated by fibers, and resembles the virus SSV1, the type member of the Fuselloviridae, isolated from Sulfolobus shibatae. Sensitivity of the virus-like particle to organic solvents and detergents suggested that the envelope of PAV1 may contain lipids in addition to proteins. It contains a double-stranded circular DNA of 18 kb which is also present in high copy number in a free form in the host cytoplasm. No integrated form of the PAV1 genome could be detected in the host chromosome. Under standard growth conditions, the host cells continuously release PAV1 particles into the culture supernatant without spontaneous lysis, with a maximum reached in the late stationary phase. UV, gamma irradiation, treatment with mitomycin C, and various physiological stresses had no effect on PAV1 production. Screening of a large number of Thermococcales isolates did not permit to find a sensitive host. These results suggest that PAV1 persists in the host strain in a stable carrier state rather than a prophage.

DNA↗

[Lactate measurements and acid-base balance in cord blood].

OBJECTIVE: To compare two techniques of lactate measurements in cord blood: either by electrochemical strip method with Lactate Pro of KDK in the umbilical artery alone (series 1) or by enzymatic method with Rapid lab Analyzer of Bayer in the two vessels (series 2) with acid base balance being also determined. SUBJECTS AND METHODS: Series 1 included 353 neonates with a mean gestational age of 37 (+/- 3.6) weeks and series 2 included 410 newborns with a mean gestational age of 38 (+/- 3.1) weeks. RESULTS: Data was presented as mean and SD. In the first series mean umbilical artery lactate concentration was 3.71 (+/- 1.81) mmol/l. In the second series mean umbilical artery blood gas and lactate levels were as follows: pH = 7.25 (+/- 0.9), pCO2 = 6.55 (+/- 1.39) kPa; BD = 6.61 (+/- 3.33) mmol/l, lactate 3.92 (+/- 1.81) mmol/l. The 3rd percentile of pH was 7.05 whereas the 97th percentile of lactate was 7.54 mmol/l. There was a close correlation between lactate and pH, and lactate and BD. Lactate concentration was higher in case of instrumental delivery compared to spontaneous one: 4.65 versus 3.76 mmol/l (p = 0.0001, Student test). No perfect correlation was found between lactate level and neonatal outcome but there was not a significant number of neonates with immediate complication. CONCLUSION: Lactate measurements obtained with single use strip method are valuable and easy to perform.

Acid-Base Equilibrium↗

The neuropeptide calcitonin gene-related peptide differently modulates proliferation and differentiation of smooth muscle cells in culture depending on the cell type.

Calcitonin gene-related peptide (CGRP) is a neuropeptide present around vasculature very early during development, when smooth muscle cells (SMC) are still proliferating and not yet totally differentiated. We investigated the effects of CGRP on proliferation and differentiation of SMC in culture; 10(-7) M CGRP added in the medium of cultured smooth muscle cells every 2 days did not significantly changed cells growth rate in 1% FCS. At the opposite, this treatment modulated proliferation of cells grown in 10% FCS medium. Two distinct populations of SMC with different growth rates were obtained from our primary cultures. SMC which proliferated slowly in the presence of 10% fetal calf serum (FCS) had growth rates positively influenced by CGRP. The quantity of alpha-smooth actin expressed by these cells was not influenced by the peptide. On the contrary, SMC which proliferated more rapidly in 10% FCS medium had growth rate inhibited by CGRP. In these cells, CGRP significantly reduced the amount of expressed alpha-smooth actin, an index of SMC differentiation. In both cases, the peptide significantly increased the level of mRNA for all the actin genes. In the light of this dual role of CGRP, it can be presumed that this peptide controls smooth muscle cells proliferation and differentiation in vivo and could thus regulate the homeostasis of the vessel wall.

Actins↗

alpha(v)beta(3) Antagonists based on a central thiophene scaffold.

A series of novel, highly potent alpha(v)beta(3) antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and beta-amino acids were explored with respect to inhibition of alpha(v)beta(3) mediated cell adhesion and selectivity versus alpha(IIb)beta(3) binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis.

Animals↗

Induction of adult-like antibody, Th1, and CTL responses to measles hemagglutinin by early life murine immunization with an attenuated vaccinia-derived NYVAC(K1L) viral vector.

Although initially developed in adult animals, novel viral vectors expressing recombinant measles antigens must eventually prove their success in the early life setting, where the efficacy of the currently used live-attenuated measles virus vaccine is limited. The immunological requirements for vaccine candidates include the generation of protective antibody responses as well as the induction of Th1 and cytotoxic T lymphocytes (CTL) responses, which is challenging in the neonatal setting. Here, we report that young BALB/c mice immunized with a single dose of a vaccinia-based NYVAC(K1L) vector generate adult-like antihemagglutinin (HA) antibody responses as well as adult-like Th1 and CTL responses. Despite this strong immunogenicity in early life, antibody responses (but not T-cell responses) to a single dose of NYVAC(K1L)-HA remained susceptible to inhibition by preexisting measles antibodies, calling for use of prime-boost strategies. NYVAC(K1L)-HA is the first attenuated live viral vector demonstrated as capable of inducing adult-like antibody, Th1, and CTL responses against measles in an early life murine immunization model, a capacity previously only reported for measles DNA vaccines.

Animals↗

[Myelodysplastic syndromes. Diagnosis and care in patients over 70 years of age].

A FREQUENT CONDITION IN GERIATRICS: Myelodysplastic syndromes comprise a group of bone marrow disorders characterized by abnormal hematopoetic stem cell clones. They are generally observed after 60 years of age with a peak frequency in the 70-80 year age group. Prevalence is probably underestimated and diagnosis is commonly made in geriatric wards. DIAGNOSIS: Clinical presentations vary widely, making diagnosis a difficult task. Cytology studies play a predominant role. Recent progress in our understanding of myelodysplastic syndromes have been achieved with cytogenic and molecular biology techniques, although the diagnostic procedures and management of elderly subjects have changed little. DISEASE COURSE AND TREATMENT: Prognosis of myleodysplastic syndromes is highly variable and mainly depends on the type of syndrome according to the international FAB classification. Therapeutic management in patients over 70 is limited in most cases to symptomatic treatment, principally with transfusional support.

Age Factors↗

[Management of DNA banks: ethical concerns].

With the creation of DNA banks, short and long-term studies can be conducted on the DNA of many individuals using stored cells and tissues. These studies allow an analysis of the pathophysiological impact of genetics and help define individual markers predictive of risk. Genome analysis is thus an important advance in medical science, providing essential information for establishing appropriate measures to slow disease development, limit severity or improve safe recovery. The use of genetic results may however have an adverse effect in certain situations if the genetic information collected were deviated from its purely medical purpose under the influence of social, occupational or economic factors. The aim of our study was to analyse the ethical challenges linked to the implementation of DNA banks in France, particularly to see how to maintain the concept of individual protection in biomedical research within the patient-physician relationship in the current context of legal and administrative regulations in France. In this study, we discuss a set of criteria which should be systematically evaluated in information collection and consent procedures prior to blood or tissue procurement for DNA bank purposes.

Biological Specimen Banks↗

The pharmacological profile of a novel norpregnance progestin (trimegestone).

Trimegestone is a novel norpregnane progestin that is being developed, in combination with estradiol, for the treatment of menopausal symptoms. The pharmacological characteristics of trimegestone have been evaluated in both in vitro and in vivo test systems, and compared with reference progestins. Interaction with hormonal steroid receptors from animal tissues and with human recombinant receptors in vitro has demonstrated that trimegestone has a high specificity and potency for the progesterone receptor, no affinity for the estrogen receptor, and weak affinity for androgen, glucocorticoid and mineralocorticoid receptors. With respect to progestomimetic activity in vivo, trimegestone was more potent than reference progestins in the endometrial transformation test in the rabbit, preventing the uterotrophic effect of estradiol in the immature mouse bioassay, and had more effect on traumatic deciduoma formation and greater oral antiovulatory activity in the rat. In vivo, trimegestone effectively maintained pregnancy in the rat, but was devoid of any uterotrophic activity. Trimegestone showed no androgenic, glucocorticoid, antiglucocorticoid or mineralocorticoid activity, but did show some antiandrogenic and antimineralocorticoid activity at higher doses. Administration of trimegestone to ovariectomized rats, in combination with estradiol, inhibited the uterotrophic effects of estradiol. At doses up to 1 mg/kg intravenously and 30 mg/kg orally, trimegestone was not associated with any unwanted pharmacological effects. Overall, the results show trimegestone to have a favorable pharmacological profile with potent progestomimetic activity.

Administration, Oral↗

Are personality disorders more frequent in early onset geriatric depression?

This preliminary study evaluates the prevalence of personality disorders (PD) in a sample of 37 elderly recovered depressed and non-demented patients, using the French version of the Vragenlijst voor Kenmezken van de Persoonlijkheid (VKP) or Questionnaire on Personality Traits (QPT). The prevalence of definite personality disorder was 65% with predominance of Cluster C and particularly dependent and avoidant PD. The rate of PDs was higher in early onset (73%) than in late onset (45%) geriatric depression, even though there is only a trend towards statistical significance (Chi square = 2.588, p = 0.107). These results are consistent with those of previous reports using different PD assessment methods, supporting evidence that the QPT could be useful in PD assessment of elderly French speaking patients.

Age Factors↗

[Informed consent: what is the question? Correlation between practice and theory].

Informed consent in medical or human experimentation is a concept generally accepted by most doctors. The foundation of informed consent is self-determination and, in the legal setting of France, contractual agreement. The practical application of informed consent in medical specialities such as psychiatrics or intensive care raises difficult problems subject to much debate. Contemporary history would suggest that the strength of informed consent may be highly insufficient to avoid the risk of dictated power dominating-patients. In order to find a solution to these problems, the field of action of informed consent must be widened. We propose here to define informed consent as one of many means to defend patient dignity and human rights.

Emergency Medicine↗