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Biomedical subjects

F Bertrand

Publications and source records attributed to F Bertrand.

At least 19 recordsLinked to original sources

Optimization and scale-up of a fluid bed tangential spray rotogranulation process.

The production of pellets in the pharmaceutical industry generally involves multi-step processing: (1) mixing, (2) wet granulation, (3) spheronization and (4) drying. While extrusion-spheronization processes have been popular because of their simplicity, fluid-bed rotogranulation (FBRG) is now being considered as an alternative, since it offers the advantages of combining the different steps into one processing unit, thus reducing processing time and material handling. This work aimed at the development of a FBRG process for the production of pellets in a 4.5-l Glatt GCPG1 tangential spray rotoprocessor and its optimization using factorial design. The factors considered were: (1) rotor disc velocity, (2) gap air pressure, (3) air flow rate, (4) binder spray rate and (5) atomization pressure. The pellets were characterized for their physical properties by measuring size distribution, roundness and flow properties. The results indicated that: pellet mean particle size is negatively affected by air flow rate and rotor plate speed, while binder spray rate has a positive effect on size; pellet flow properties are enhanced by operating with increased air flow rate and worsened with increased binder spray rate. Multiple regression analysis enabled the identification of an optimal operating window for production of acceptable pellets. Scale-up of these operating conditions was tested in a 30-l Glatt GPCG15 FBRG.

Acetaminophen↗

Flow of wet granular materials.

The transition from frictional to lubricated flows of a dense suspension of non-Brownian particles is studied. The pertinent parameter characterizing this transition is the Leighton number Le=eta(s)gamma / sigma, the ratio of lubrication to frictional forces. Le defines a critical shear rate below which no steady flow without localization exists. In the frictional regime the shear flow is localized. The lubricated regime is not simply viscous: the ratio of shear to normal stresses remains constant and the velocity profile has a universal form in both frictional and lubricated regimes. Finally, a discrepancy between local and global measurements of viscosity is identified, which suggests inhomogeneity of the material under flow.

Journal Article↗

Comparative mapping of ZYMV resistances in cucumber (Cucumis sativus L.) and melon (Cucumis melo L.).

Zucchini yellow mosaic virus (ZYMV) routinely causes significant losses in cucumber ( Cucumis sativus L.) and melon ( Cucumis melo L.). ZYMV resistances from the cucumber population 'TMG1' and the melon plant introduction (PI) 414723 show different modes of inheritance and their genetic relationships are unknown. We used molecular markers tightly linked to ZYMV resistances from cucumber and melon for comparative mapping. A 5-kb genomic region (YCZ-5) cosegregating with the zym locus of cucumber was cloned and sequenced to reveal single nucleotide polymorphisms and indels distinguishing alleles from ZYMV-resistant (TMG1) and susceptible (Straight 8) cucumbers. A low-copy region of the YCZ-5 clone was hybridized to bacterial artificial chromosome (BAC) clones of melon and a 180-kb contig assembled. One end of this melon contig was mapped in cucumber and cosegregated with ZYMV resistance, demonstrating that physically linked regions in melon show genetic linkage in cucumber. However the YCZ-5 region segregated independently of ZYMV resistance loci in two melon families. These results establish that these sources of ZYMV resistances from cucumber TMG1 and melon PI414723 are likely non-syntenic.

Chromosome Mapping↗

[Elderly patients presenting with fever and respiratory problems in an intensive care unit. Diagnostic, therapeutic and prognostic impact of a systematic infectious disease consultation].

OBJECTIVE: To measure the impact of an infectious disease consultation on the morbidity and mortality in patients aged over 75 presenting with fever and respiratory signs and treated with antibiotics in an intensive care unit. METHOD: Retrospective study comparing two groups of patients having been seen or not by an infectious disease specialist within the first 24 hours of hospitalisation. The data available before prescription of the antibiotherapy by the intensive care physician were collected, together with the diagnostic and therapeutic proposals of the infectious disease specialist. Morbidity and mortality were assessed from the medical files and nurses charts and included: duration of fever and hospitalisation, complications with antibiotherapy and venous catheters and the cause or causes of death. RESULTS: 169 patients were included, 115 of whom had been seen (study group) and 54 who had not bee seen (control group) by an infectious disease specialist. Sixty-six percent of the infectious disease specialists (76/115) proposed a differential diagnosis, although a diagnostic re-assessment was effective for only 22% of the patients in the control group (p< 0.01). A 50% reduction in antibiotic prescriptions was observed in the study group. The duration of hospitalisation was greater in the study group than in the control group (a mean of 10 versus 7 days, p<0.01), but was unrelated to the consultation with a specialist. The same result was observed with the complications of venous catheterism (16 versus 2 cases, p =0.04). The rate of mortality was of 13% in both groups. CONCLUSION: The over-zealous diagnoses of infection are the primary cause of over-prescription of antibiotics. Despite the population studied, considered as fragile, the 50% reduction in antibiotics is without any negative prognostic impact.

Aged↗

Relevance and complications of intravenous infusion at the emergency unit at Nice university hospital.

OBJECTIVE: Insertion of peripheral venous catheters (PVCs) is current practice within the hospital environment and particularly in the emergency department (ED). This simple yet invasive technique may result in venous thrombosis, infection or mechanical complications. We conducted a prospective study at the Nice University Hospital ED in order to determine the frequency, relevance and complications of peripheral venous cannulation. PATIENTS AND METHODS: Fourteen 24 h periods were surveyed over the months of May and June 2000, during which 2515 patients over 16 years of age attended the unit. Demographic and medical data were recorded for every patient who received a PVC. These patients were followed at 12 h intervals until the catheter was removed. Reasons for PVC, time left in place, and eventual complications were recorded. Justification for PVC was evaluated upon arrival at the ED, upon exiting the ED and in some cases within the hospital ward. RESULTS: Six hundred and thirty of 2515 patients (25%) received a PVC (290 women (46%) and 340 men (54%); meanage 58 years). Indication for the PVC was considered unjustified in 24.8% of cases upon arrival at the ED, and 33.8% upon leaving the ED. Upon admission in a hospital ward after passing through the ED, out of 318 patients, the PVC was left in place for no reason in 63 (20%). Overall, 390 PVCs were followed until the time of their removal. Mean duration of IV infusion was 28 h. Among these 390 patients, 62 (15.9%) developed complications, of which 54 (13.6%) had thrombophlebitis and 9 (2.3%) developed local infection. Mean duration of PVC left in place for patients with complications was 50 h vs 25 h for patients with no complications (P<0.001). CONCLUSION: Insertion of a PVC is common practice especially in EDs. The excessive use of this procedure leads to extra cost and iatrogenic complications. A renewed definition of its indication and raised awareness among hospital staff concerning the risks involved with this standard procedure should result in less use of PVC and fewer complications.

Catheterization, Peripheral↗

[Periodontal disease in Belgian adults].

BACKGROUND: To date, no epidemiological study has been published on the periodontal health of the Belgian population. The aim of this study was to rectify this situation and determine the extent of the problem in Belgium. METHODS: A prevalence survey was carried out in a representative sample of employees of the Catholic University of Louvain. A total of 402 people aged between 35 and 65 were examined. Periodontal suffering was estimated using the CPITN index (WHO), which determines the most affected sextant of a mouth in order to assign a code to the mouth as a whole. At the same time, treatment needs were evaluated. RESULTS: Only one subject was considered healthy, i.e. there was no bleeding of the gums in any part of the mouth. At the same time, 41.4% of the subjects examined exhibited a deep periodontal pocket in at least one sextant of the mouth likely to progress to the loss of the teeth. Many mouths (28.5%), which were free from moderate or deep pockets, had to be scaled and polished or to be treated in order to eliminate other factors which could lead to a build-up of tartar. CONCLUSION: In this study population representative of a socio-economically favored stratum of the Belgian population, we observed a high prevalence of periodontal diseases, grading from mild chronic gingivitis to the deep cavities which are observed when the bone supporting the tooth has been lost. At the same time, we uncovered many needs for periodontal care, ranging from instruction on how to control the dental plaque to specialized periodontal care via careful scaling and polishing.

Adult↗

Coexistence of liquid and solid phases in flowing soft-glassy materials.

Magnetic-resonance-imaging rheometrical experiments show that concentrated suspensions or emulsions cannot flow steadily at a uniform rate smaller than a critical value (gamma(c)). As a result, a "liquid" region (sheared rapidly, i.e., at a rate larger than gamma(c)) and a "solid" region (static) coexist. The behavior of the fluid in the liquid region follows a simple power-law model, while the extent of the solid region increases with the degree of jamming of the material.

Journal Article↗

[Motives for the prescription of antibiotics in the emergency department of the University Hospital Center in Nice. A prospective study].

OBJECTIVES: Since April 1999, we have set-up an infectious disease consultation in the emergency unit of the University Hospital in Nice. Unjustified antiobiotherapy is often initiated. We therefore conducted a survey to study the motives and validity of antibiotic prescriptions. METHOD: This prospective study was conducted in two phases. The first consisted in asking the emergency physicians prescribing antibiotics to fill-in a questionnaire giving information on the diagnosis established and the antiobiotherapy proposed. In the second phase, the diagnoses and corresponding treatments were submitted to 4 experts who assessed the acceptability of the diagnoses and the antibiotics prescribed. The experts only had access to the clinical and para-clinical data available. Moreover, their therapeutic judgement was based on previously published consensuses. RESULTS: The 6-month survey collected 117 questionnaires that could be analysed. The rate of error in diagnosis was of 33% (39/117). Thoracic x-rays could not be interpreted in 11% of cases. In single variant analysis, factors of erroneous diagnosis were due to its interpretation by an internist, the diagnostic category of "broncho-pulmonary infections" and the lack of documentation. In multi variant analysis, only the lack of documentation was related to erroneous diagnosis (OR = 5.5; IC 95% (2.03; 15.30), p < 0.0002). The rate of antibiotherapy not adapted to the diagnosis made by the physician was of 32% (37/117). In 24 cases the modalities of the prescription were incorrect and in 13 cases the prescription was unjustified. Only the status of the prescriber (internist) was statistically associated with an antibiotherapy not adapted to the diagnosis (OR = 2.2; IC 95% (0.93; 5.26), p < 0.05). CONCLUSION: Unjustified antibiotherapy in an emergency unit is generally due to erroneous diagnosis of infection. The lack of documentation and inexperience of the prescribers appear to be the two elements contributing to unjustified antibiotherapy.

Anti-Bacterial Agents↗

Grafts of fetal septal cells after cholinergic immunotoxic denervation of the hippocampus: a functional dissociation between dorsal and ventral implantation sites.

Three-month-old Long-Evans rats were subjected to intraseptal infusions of 0.8 microg of 192 IgG-saporin followed, 2 weeks later, by intrahippocampal suspension grafts containing fetal cells from the medial septum and the diagonal band of Broca. The suspensions were implanted in the dorsal or the ventral hippocampus. Sham-operated and lesion-only rats were used as controls. Between 18 and 32 weeks after grafting, all rats were tested in a water maze (using protocols placing emphasis on reference memory or on working memory) and an eight-arm radial maze. The lesion produced extensive cholinergic denervation of the hippocampus, as evidenced by reduced acetylcholinesterase-positivity and acetylcholine content. Depending upon their implantation site, the grafts restored an acetylcholinesterase-positive reinnervation pattern in either the dorsal or the ventral hippocampus. Nevertheless, the grafts failed to normalize the concentration of acetylcholine in either region. The cholinergic lesion impaired working memory performance in both the water maze and the radial maze. To a limited degree, reference memory was also altered. Grafts placed in the ventral hippocampus had no significant behavioral effect, whereas those placed in the dorsal hippocampus normalized working memory performance in the water maze. Our data show that infusion of 192 IgG-saporin into the septal region deprived the hippocampus of its cholinergic innervation and altered spatial working memory more consistently than spatial reference memory. Although the cholinergic nature of the graft-induced reinnervation remains to be established more clearly, these results further support the idea of a functional dissociation between the dorsal and the ventral hippocampus, the former being preferentially involved in spatial memory.

Animals↗

[Periodontal health and care needs in a sample of the Belgian population].

An epidemiological survey was carried out of among staff members of the Catholic University of Louvain. A total of 402 subjects, age 35 to 65, were examined. Periodontal lesions were estimated using the CPITN index (WHO). Only one subject presented no signs of gingival bleeding in any part of the mouth. 41.4% of the subjects presented a deep periodontal pocket in at least one sextant. Many subjects, although not presenting deep or moderately deep periodontal pockets (28.5%) needed scaling and rootplanning or other treatments to eliminate plaque retentive factors. In this sample, representing a socio-economically favoured segment of the population, we revealed a significant prevalence of periodontal disease from mild chronic gingivitis to deep pockets. Requirements in terms of care are considerable, ranging from oral hygiene instruction to control plaque to specialised care.

Adult↗

Smad7 inhibits the survival nuclear factor kappaB and potentiates apoptosis in epithelial cells.

In this study, we examined the effect of the stable expression of Smad7 in two different cell lines on apoptosis induced by various stimuli including TGF-beta, serum withdrawal, loss of cell adhesion (anoikis) and TNF-alpha. Smad7 increased TGF-beta-mediated apoptosis in Mv1Lu cells as well as anoikis and/or serum withdrawal-induced apoptosis in Mv1Lu and MDCK cells. Smad7 markedly decreased the activity of the survival NF-kappaB transcription factor in MDCK cells. Interestingly, the stable expression of oncogenic Ras in MDCK cells which suppressed Smad7 inhibition of NF-kappaB also suppressed Smad7 potentiation of serum withdrawal-induced apoptosis and anoikis. In addition, Smad7 inhibited TNF-alpha stimulation of NF-kappaB and increased TNF-alpha-mediated apoptosis in MDCK cells. Our results provide the first evidence that Smad7 induces sensitization of cells to different forms of cell death. They moreover demonstrate that Smad7 inhibits the survival NF-kappaB factor, providing a potential mechanism whereby Smad7 potentiates cell death.

Animals↗

Insulin and IGF-1 stimulate the beta-catenin pathway through two signalling cascades involving GSK-3beta inhibition and Ras activation.

We examined the interplay between the insulin/IGF-1- and beta-catenin-regulated pathways, both of which are suspected to play a role in hepatocarcinogenesis. Insulin and IGF-1 stimulated the transcription of a Lef/Tcf-dependent luciferase reporter gene by 3-4-fold in HepG2 cells. This stimulation was mediated through the activation of phosphatidylinositol 3-kinase (PI 3-K)/Akt and the inhibition of glycogen synthase kinase-3beta (GSK-3beta) since the effects of insulin and IGF-1 were inhibited by dominant-negative mutants of PI 3-K or Akt and an uninhibitable GSK-3beta. Together with inhibiting GSK-3beta, insulin and IGF-1 increased the cytoplasmic levels of beta-catenin. The PI 3-K/Akt/GSK-3beta pathway was not the sole to mediate insulin and IGF-1 stimulation of Lef/Tcf-dependent transcription. The Ras signalling pathway was also required as (i) the stimulatory effects of insulin and IGF-1 were inhibited by dominant-negative Ras or the MEK1 inhibitor PD98059 and (ii) activated Ha-Ras or constitutively active MEK1 synergized with catalytically inactive GSK-3beta to stimulate Lef/Tcf-dependent transcription. This study provides the first evidence that insulin and IGF-1 stimulate the beta-catenin pathway through two signalling cascades bifurcating downstream of PI 3-K and involving GSK-3beta inhibition and Ras activation. These findings demonstrate for the first time the ability of insulin and IGF-1 to activate the beta-catenin pathway in hepatoma cells and thereby provide new insights into the role of these factors in hepatocarcinogenesis.

Calcium-Calmodulin-Dependent Protein Kinases↗

Cognitive performances and locomotor activity following dentate granule cell damage in rats: role of lesion extent and type of memory tested.

Intradentate injection of colchicine is one of the techniques used to destroy granule cells. This study compared the behavioral effects of various amounts of colchicine (1.0, 3.0, and 6.0 microg; Col 1, Col 3, and Col 6, respectively) injected into the dentate gyrus of adult Long-Evans male rats. Starting 10 days after lesion surgery, behavioral testing assessed home-cage and open-field locomotion, alternation in a T-maze, water-maze, and radial-maze learning according to protocols placing emphasis on reference, and working memory. All of these tasks are sensitive to hippocampal disruption. Histological verifications showed that the extent of the lesions depends on the dose of colchicine (index of dentate gyrus shrinkage: -33% in Col 1, -54% in Col 3, and -67% in Col 6 rats). Colchicine dose-dependently increased nocturnal home cage activity (an effect found 10 days but not 5 months after surgery), but had no significant effect on open-field locomotion or T-maze alternation. A dose-dependent reference memory impairment was found during the acquisition of spatial navigation in the water maze; Col 3 and Col 6 rats were more impaired than Col 1 rats. During the probe trial (platform removed), control rats spent a longer distance swimming over the platform area than all rats with colchicine lesions. In the working memory version of the test, all rats with colchicine lesions showed significant deficits. The deficits were larger in Col 3 and Col 6 rats compared to Col 1 rats. The lesions had no effect on swimming speed. In the radial-maze test, there was also a dose-dependent working memory impairment. However, reference memory was disrupted in a manner that did not differ among the three groups of lesioned rats. Our data are in line with the view that the dentate gyrus plays an important role in the acquisition of new information and is an integral neural substrate for spatial reference and spatial working memory. They also suggest that damage to granule cells might have more pronounced effects on reference than on working memory in the radial maze. Finally, they demonstrate that part of the variability in the conclusions from previous experiments concerning the role of granule cells in cognitive processes, particularly in spatial learning and memory, may be due to the type of tests used and/or the extent of the damage produced.

Animals↗

Effects of MDL 73005 on water-maze performances and locomotor activity in scopolamine-treated rats.

The stimulation of 5-HT1A receptors in the raphe or their blockade in the hippocampus can reduce cognitive deficits induced by blockade of muscarinic receptors in the hippocampus. We investigated the effects of MDL 73005 (8-[2-(2,3-dihydro-1,4-benzodioxin-2-ylmethylamino) ethyl]-8-azaspiro[4,5] decane-7,9-dione methyl sulphonate), an agonist at 5-HT1A somatodendritic autoreceptors and an antagonist at postsynaptic 5-HT1A receptors in rats treated systemically with scopolamine. Spatial memory was assessed in a water maze using protocols testing reference and working memory. Home cage locomotor activity was also determined. Working memory and locomotor activity were evaluated before and after para-chlorophenylalanine (pCPA) treatment. Scopolamine produced a weak impairment of reference memory at 0.5 mg/kg, and a more pronounced impairment of working memory at 0.25 and 0.5 mg/kg. MDL 73005 alone (2 mg/kg, i.p.) had no effect, but prevented the memory impairments induced by 0.25 mg/kg of scopolamine. Scopolamine induced hyperlocomotion. MDL 73005 alone did not affect locomotor activity, but exacerbated the hyperlocomotion induced by 0.5 mg/kg of scopolamine. pCPA did not abolish the effects of MDL 73005, suggesting that these effects were not due to an action at presynaptic receptors, or even that they involved receptors other than serotonergic ones (e.g., D2). In conclusion, MDL 73005 is able to antagonise moderate spatial memory dysfunctions induced by systemic muscarinic blockade.

Animals↗

[Evaluation of a hospitalization unit opened during the winter influenza epidemic of 1999-2000].

PURPOSE: Last winter, a great many patients with influenza-like infection were admitted to our hospital, leading us to open a specific unit for 6 weeks. We report the evaluation of medical care given to these patients. METHODS: Useful data for evaluating care to patients presenting respiratory infections were determined beforehand by the retrospective analysis of patients' charts. RESULTS: Fifty-seven out of 185 admitted patients (31%) had infectious respiratory symptoms. The mean age was 81 years. Six cases of influenza virus infection, 43 cases of viral bronchitis, six cases of bacterial pneumonia, one superinfected asthma and one septic shock were diagnosed. All patients presented with cardiac and/or chronic pulmonary diseases. Influenza vaccination had been performed in 28 patients (49%). Before hospitalisation, 30 patients (52%) had received antibiotics, and 17 (30%) a steroid therapy. In contrast, only 12 patients (21%) have received anti-infective agents during the hospitalisation. Twenty-five patients were able to go back home and a nursing home was required for 27 patients (47%); five patients died. Tools for improving this specific department in a public hospital are discussed. CONCLUSION: Vaccinations in the elderly appear to be poorly utilized; meanwhile, antibiotic treatments, as well as steroid therapy, are overused. Managing epidemic infections requires attention from the public hospital system.

Aged↗

Fluorescence in situ hybridization and immunohistochemical assays for HER-2/neu status determination: application to node-negative breast cancer.

BACKGROUND: HER-2/neu (ERBB2) gene amplification and/or overexpression is a major event in human breast tumorigenesis. HER-2/neu gene alterations have been the most frequently assessed prognostic factors during the last 10 years in breast cancer and have recently emerged as a management decision tool and a therapeutic target. There is still controversy over the best method to determine whether a tumor is HER-2/neu positive. Because of the increasing demand for HER-2/neu gene status determination in clinical practice, we compared HER-2/neu gene alterations at the DNA level (gene amplification) and the protein level (overexpression) in a panel of patients with lymph node-negative breast cancer who had received local radiotherapy alone, with no adjuvant therapy. METHODS: We tested 100 excised lymph node-negative breast tumors, using fluorescence in situ hybridization (FISH) with a biotinylated HER-2/neu DNA probe and immunohistochemical assays (IHC) with 2 different antibodies. RESULTS: The FISH frequency of HER-2/neu gene amplification was 15%, and the IHC frequency of overexpression was 21%. CONCLUSION: Although HER-2/neu amplification by FISH and HER-2/neu overexpression by IHC correlated well in this panel of lymph node-negative breast carcinomas, there were a number of discordant cases, pointing to the important need for determining HER-2/neu alteration for the future management of HER-2/neu-based clinical applications.

Adult↗

The differential regulation of group II(A) and group V low molecular weight phospholipases A(2) in cultured rat astrocytes.

In astrocytes, cytokines stimulate the release of secretory phospholipase A(2) (sPLA(2)) activity and group II(A) sPLA(2) expression. This paper reports that two sPLA(2) isoforms, group II(A) and group V, are in fact expressed by astrocytes. Our studies showed that tumor necrosis factor alpha (TNFalpha) enhanced the mRNA of both isoforms, but the time courses of enhancement differed; group V was induced much faster than group II(A). Moreover, TNFalpha stimulated both the NF-kappaB and mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase, c-Jun NH(2)-terminal kinase, and p38 MAP kinase) signaling pathways in astrocytes. Interestingly, PI 3-kinase activity also was enhanced by TNFalpha, and NF-kappaB pathway was involved in mediating its effect. Specific inhibitors were used to show that both extracellular signal-regulated kinase and p38 MAP kinase may contribute to the effect of TNFalpha and that blocking phosphatidylinositol 3-kinase activity fully reversed the effect of TNFalpha. Furthermore, in astrocytes, TNFalpha-induced release of sPLA(2) activity was partially reversed by thyroid hormone and almost abolished by growth factors. This phenomenon was accompanied by a less marked increase in both group II(A) and group V sPLA(2) mRNA. In the presence of growth factors, the increase in group V mRNA was inhibited early and transiently, in contrast to what was observed with group II(A), which was more persistently inhibited. Although a transcriptional effect of thyroid hormone or growth factors in astrocytes cannot be definitively excluded, both types of factor interfered with sPLA(2) expression in a manner suggesting the existence of regulation of post-transcriptional events.

Animals↗