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Biomedical subjects

Pierre Gillet

Publications and source records attributed to Pierre Gillet.

At least 19 recordsLinked to original sources
PubMed2006

Gene transfer with HSP 70 in rat chondrocytes confers cytoprotection in vitro and during experimental osteoarthritis.

Osteoarthritis is characterized by a gradual degradation of extracellular matrix, resulting from an excess of chondrocyte cell death, mainly due to an increase in apoptotis. Recent studies have revealed the essential role of HSP70 in protecting cells from stressful stimuli. Therefore, overexpressing HSP70 in chondrocytes could represent a good strategy to prevent extracellular matrix destruction. To this end, we have developed a vector carrying HSP70/GFP, and transduced chondrocytes were thus more resistant to cell death induced by mono-iodoacetate (MIA). To overcome the barrier-effect of matrix, we investigated the efficacy of plasmid delivery by electroporation (EP) in rat patellar cartilage. Two days after EP, 50% of patellar chondrocytes were HSP/GFP+. After 3 months, long-term expression of transgene was only depicted in the deep layer (20-30% positive cells). HSP70 overexpression inhibited the natural endochondral ossification in the deep layer, thus leading to a lesser decrease in chondrocyte distribution. Moreover, overexpression of HSP70, after a preventive EP transfer in rat patella, was sufficient to decrease the severity of osteoarthritis-induced lesions, as demonstrated histologically and biochemically. In conclusion, intracellular overexpression of HSP70, through EP delivery, could protect chondrocytes from cellular injuries and thus might be a novel chondroprotective modality in rat OA.

Animals↗
PubMed2006

Revision of the Belgian Nursing Minimum Dataset: From data to information.

The Ministry of Public Health commissioned a research project to the Catholic University of Leuven and the University Hospital of Liège to revise the Belgian Nursing Minimum Dataset (B-NMDS). The study started in 2000 and will end with the implementation of the revised B-NMDS in January 2007. The study entailed four major phases. The first phase involved the development of a conceptual framework based on a literature review and secondary data analysis. The second phase focused on language development and development of a data collection tool. The third phase focused on data collection and validation of the new tool. In the fourth phase the validity and reliability of the dataset was tested. The new dataset is without avail if it is not leading to new information. Four applications of the dataset has been defined from the beginning: evaluation of the appropriateness of stay (AEP) in the hospital, nurse staffing, hospital financing and quality management. The aim of this paper is to describe how the B-NMDS can contribute to each of these applications.

Belgium↗
PubMed2005

Revising the Belgian Nursing Minimum Dataset: from concept to implementation.

The process of revising the Belgian Nursing Minimum Dataset (B-NMDS) started in 2000 and entailed four major phases. The first phase (June-October 2002) involved the development of a conceptual framework based on a literature review and secondary data analysis. The Nursing Interventions Classification (NIC) was selected as a framework for the revision of the original B-NMDS. The second phase (November 2002-September 2003) focused on language development for six care programs evaluated by panels of clinical experts (N=75). These panels identified the following items as priorities for the revised B-NMDS: hospital financing, nurse staffing allocation, assessment of the appropriateness of hospitalisation, and quality management. During this period, we developed a draft instrument with 92 variables using the NIC. This led to an alpha version of a revised B-NMDS. The third phase (October 2003-December 2004) focused on data collection and validation of the new tool. The revised B-NMDS (alpha version) was tested in 158 nursing wards in 66 Belgian hospitals from December 2003 until March 2004. This test generated data for some 95,000 in-patient days. The interrater reliability of the revised B-NMDS was assessed. The criterion-related validity of the revised B-NMDS was compared to that of the original B-NMDS. The discriminative power of the revised B-NMDS was also assessed to select the most relevant variables for data collection. This resulted in a beta version of the revised B-NMDS in December 2004. The records of the revised B-NMDS were linked to the Hospital Discharge Dataset and other mandatory datasets to integrate the revised B-NMDS into the overall healthcare management system. The fourth phase (January 2005-December 2005) is presently focusing on information management. Nationwide implementation is foreseen by January 2007.

Belgium↗
PubMed2005

Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity.

OBJECTIVE: To determine the magnetic resonance imaging (MRI), macroscopic, and microscopic characteristics of synovial membrane inflammation, to study the relationship between disease severity and the degree of synovial inflammation on MRI and on macroscopic and microscopic examination, and to look for colocalization of chondral lesions and synovial inflammation. METHODS: Thirty-nine patients with knee osteoarthritis (OA) were classified into 2 groups according to the severity of cartilage lesions as revealed by chondroscopy. Group 1 (n = 14) had mild cartilage lesion(s) without exposure of subchondral bone. Group 2 (n = 25) had severe cartilage lesion(s) with focal or diffuse exposure of subchondral bone. Synovitis was evaluated on T1-weighted MRI sequences according to the degree of synovial thickening on a 4-point scale (ranging from 0 to 3) in 5 regions of interest. Synovial membrane was macroscopically scored, and biopsies were performed on the 5 preselected sites for histologic scoring. RESULTS: The mean +/- SD synovial thickening score on MRI was 1.55 +/- 0.90, with no significant difference between groups 1 and 2. Intra- and interobserver reproducibility of the total synovial score was excellent, and interobserver reproducibility of the MRI grade was good. Synovitis was diffuse and associated with chondral lesions only in the medial femorotibial compartment (r = 0.49, P = 0.001). The degree of synovial thickening on MRI correlated with qualitative macroscopic analysis (r(s) = 0.58, P < 0.001) and with microscopic features (synovial lining cells [r(s) = 0.23, P < 0.007], surface fibrin deposition [r(s) = 0.12, P < 0.01], fibrosis [r(s) = 0.31, P < 0.006], edema [r(s) = 0.17, P = 0.07], congestion [r(s) = 0.30, P < 0.005], and infiltration [r(s) = 0.46, P < 0.0001]). Fibrin and infiltration parameters were more severe in end-stage disease (P = 0.009 and P = 0.02, respectively). CONCLUSION: Synovitis may be present from the onset of OA and may be evaluated on MRI. MRI evaluation of synovitis could be used to classify OA patients in clinical trials and could help to identify those who could benefit from synovium-targeted therapy.

Arthroscopy↗
PubMed2004

Effect of proteoglycan depletion on T2 mapping in rat patellar cartilage.

PURPOSE: To evaluate experimentally the sensitivity of T2 mapping with magnetic resonance (MR) imaging at 8.5 T in depicting variations in proteoglycan content and concurrent extracellular matrix of rat patellar cartilage. MATERIALS AND METHODS: The study was performed in 36 immature (age, 5 weeks) and 36 mature (age, 10 weeks) Wistar rats. Maintenance and care of the rats were conducted in accordance with National Institutes of Health guidelines. Fifty-six rats underwent T2 mapping in 28 right patellae degraded with hyaluronidase for 1 and 6 hours and in 28 undegraded age-matched patellae that served as controls. After MR mapping, the rats were sacrificed, and the patellae were studied histologically to evaluate proteoglycan and collagen content and collagen network organization in cartilage. Biochemical analysis was performed in 88 patellae to quantify sulfated glycosaminoglycan and hydroxyproline content. Effects of age and/or degree of degradation were evaluated after rank transformation of continuous data by using rank analysis of variance (ANOVA). Associations between continuous variables were assessed with the Spearman rank correlation coefficient. RESULTS: Results of histologic analysis showed proteoglycan loss after hyaluronidase degradation without alteration of collagen network. No significant variation in hydroxyproline sulfate content was observed with depletion of proteoglycan. Proteoglycan losses of 19% and 13%, found after 1-hour degradation in immature and mature groups, respectively, were associated with significantly increased global T2 values (ANOVA, P < .001). Six-hour degradation resulted in more severe proteoglycan losses of 45% and 53% in immature and mature groups, respectively, inducing significant increases in global T2 values in immature and mature groups (ANOVA, P < .001). Variations in T2 values between superficial and deep cartilage zones were not affected by proteoglycan depletion. CONCLUSION: In rat patellar cartilage, T2 mapping permits detection of slight or severe proteoglycan depletion and concurrent changes of extracellular matrix when age-matched samples are compared.

Analysis of Variance↗
PubMed2004

Age- and sex-stratified prevalence of physical disabilities and handicap in the general population.

BACKGROUND AND AIMS: Our aim was to provide age- and sex-stratified prevalence estimates of physical disabilities and handicap in the general Belgian population. METHODS: A cross-sectional and demographically representative health interview survey was conducted nationwide in Belgium in 1997. The 8836 persons aged 15 years and over who answered the health interview were included in this study. Seventeen items from the survey encompassing main activities of daily living (ADL) and confining were analyzed. To provide prevalence estimates as detailed as possible, neither aggregation nor dichotomization were applied. RESULTS: Women consistently reported more disability than men: mobility (p < 0.001), transfer in-out bed (p < 0.001), transfer in-out chair (p < 0.001), dressing (p = 0.004), washing hands and face (p = 0.029), getting to and using toilet (p = 0.003), continence (p < 0.001), seeing (p < 0.001) and mastication (p < 0.001). As expected, there was a marked trend for increased prevalence of disability with increasing age for both sexes. Moderate disability arose mainly from the 25-34 age group for both sexes. For both genders, severe disability appeared mainly at higher ages, particularly for the 65-74 age group. Nevertheless, the data suggest that continence problems for women, mobility and transfer issues for men, as well as mastication problems for both genders, clearly emerge earlier than age 65. Regarding handicap, observed prevalence rates were increasing, in age as was the case for disability, but no differences were found between men or women, except for confinement to house/garden, for which women presented a higher rate in general (p < 0.001) and in the 75-84 age group (p = 0.036) in particular. CONCLUSIONS: This study shows the wide range of disability types in the general population and their association with handicap. While elderly individuals consistently report higher degrees of disability and handicap, attention should also be paid to younger age groups. Disability calls for wide, coherent and relevant medical as well as social responses.

Activities of Daily Living↗
PubMed2004

Rupture of multiple tendons after levofloxacin therapy.

An 80-year-old man treated by levofloxacin developed multiple tendon ruptures. His symptoms resolved over 9 months after levofloxacin discontinuation. Nasal corticosteroid therapy, aging and chronic respiratory insufficiency were probably predisposing factors in this patient.

Aged↗
PubMed2004

Dose-response relationship for exercise on severity of experimental osteoarthritis in rats: a pilot study.

OBJECTIVE: To investigate the influence of a calibrated exercise on the progression of structural lesions in an experimental model of osteoarthritis (OA) in the rat, and to explore the effect of exercise on the level of chondrocyte caspase-dependent apoptosis and of Hsp70. METHODS: The OA model was induced by anterior cruciate ligament transection (ACLT). Rats were placed in 4 experimental groups: operated (ACLT) free moving rats, and 3 exercise groups (slight, moderate and intense) subjected to running training. Rats were killed 14 and 28 days after surgery. RESULTS: On D14 histological assessment demonstrated a beneficial influence of a slight and a moderate exercise vs control ACLT group. Hsp70 increased significantly in the moderate group vs controls. On D28, histological lesions strongly decreased in the slight and moderate exercise groups vs ACLT group, while an intense effort abolished this beneficial trend. Interestingly, the concomitant course of apoptotic events (caspase 3-positive cells) and the co-expression of Hsp70 in the various groups varied, when significant, in an inverse manner. In the intense group this overexpression was not noted, as a "burn out" appeared, thus leading to a loss of this protective effect. CONCLUSION: This study shows that a calibrated slight or moderate exercise exerts a beneficial influence on the severity of chondral lesions in ACLT rats. Conversely, a strong effort abolishes this chondroprotective effect. This effect could be related to a reduced level of chondrocyte apoptosis through anti-apoptotic capacities of stress-induced Hsp70 overexpression.

Animals↗
PubMed2004

Induction of heat shock protein 70 (Hsp70) by proteasome inhibitor MG 132 protects articular chondrocytes from cellular death in vitro and in vivo.

The aim of this work was to determine whether Hsp70 overexpression via proteasome inhibitor MG132 was able to protect chondrocytes towards mono-iodoacetate (MIA) cytotoxicity both in vitro and in vivo. In vitro, overexpression of Hsp70 via MG132 was significantly able to protect chondrocytes from MIA toxicity (MTT/LDH analyses). Hsp70 essentially mediated this chondroprotective effect as demonstrated by antisense strategy. In vivo, chondrocytic overexpression of Hsp70, after a preventive intra-articular injection of MG132 in rat knee, was sufficient to decrease the severity of OA-induced MIA lesions, as demonstrated histologically and biochemically. In conclusion, intracellular overexpression of Hsp70, through proteasome inhibition, could be an interesting tool in protecting chondrocytes from cellular injuries, either necrotic or apoptotic in nature, and thus might be a novel chondroprotective modality in rat experimental OA.

Animals↗
PubMed2004

A nation-wide project for the revision of the Belgian nursing minimum dataset: from concept to implementation.

This paper describes the process of revising the Belgian Nursing Minimum Data Set (NMDS). The study started in 2000. Implementation is planned from 2006. The project is divided in 4 major phases. The first phase (June-October 2002) implied the development of the conceptual framework based on literature review and secondary data-analysis. The Nursing Interventions Classification (NIC) was selected as framework for the revision of the NMDS. The second phase focused on the language development (November 2002 - September 2003) with panels of clinical experts (N=75) for six care programs. They indicated hospital financing, nurse staffing allocation and assessment of the appropriateness of hospitalization as priorities of a revised B-NMDS. A draft instrument with 84 variables, using NIC, was developed during this period. This leads to an alpha version of a revised NMDS. The third phase (October 2003 - December 2004) focused on the data collection and validation of the new tool. The new NMDS was tested on 158 nursing wards in 66 Belgian hospitals from December 2003 until March 2004. This test generated data for some 95.000 inpatient days. The interrater-reliability of the revised NMDS is tested. The criterion-related validity of the revised NMDS is compared with the actual NMDS. The discriminative power of the revised NMDS is tested to select the most relevant items for data collection. This will result in a beta version of revised NMDS in December 2004. The records of the revised NMDS are linked with the hospital discharge dataset and other mandatory datasets to integrate the revised NMDS in the broader health care management. The fourth phase (January-December 2005) will focus on information management.

Belgium↗
PubMed2003

Effects of antiinflammatory drugs on arthritic cartilage: a high-frequency quantitative ultrasound study in rats.

OBJECTIVE: To evaluate the ability of 55-MHz quantitative ultrasound (US) to detect the in vivo effects of experimental arthritis, as well as those of two antiinflammatory drugs, naproxen (NPX) and dexamethasone (DEX), on cartilage and subchondral bone. METHODS: Arthritis was induced in both knees of 108 rats by intraarticular injection of zymosan (ZYM). Two groups of arthritic rats (n = 36 per group) were treated daily with either NPX (10 mg/kg/day) or DEX (0.1 mg/kg/day). Using a 3-dimensional US microscope, patellae were explored in vitro on days 5, 14, and 21 after injections. US assessment included the analysis of quantitative indices of local modifications involving cartilage and bone: integrated reflection coefficient (IRC) from the cartilage surface and apparent integrated backscatter from the cartilage internal structure (cartilage matrix) (AIB(cartilage)) and the cartilage-bone interface (AIB(bone)). RESULTS: ZYM induced articular surface fibrillation that resulted in a decrease in IRC at all times (P < 0.02) and in an increase in AIB(bone) on days 5 and 14 (P < 0.005). Fibrillation was not changed by NPX administration, while it disappeared following DEX treatment. Cartilage-bone interface alterations were prevented by DEX and partially compensated for by NPX. Cartilage matrix echogenicity decreased with time in all groups due to maturation (P < 0.05), except in DEX-treated rats. CONCLUSION: Quantitative 55 MHz US allowed detection of early cartilage and bone lesions due to experimental arthritis, and also allowed detection of the effects of antiinflammatory drugs. NPX seemed to have an effect on subchondral bone lesions, but not on cartilage. DEX appeared to repair articular surface and bone, but prevented animal growth and cartilage maturation.

Animals↗
PubMed2003

Direct gene transfer into rat articular cartilage by in vivo electroporation.

To establish a system for efficient direct in vivo gene targeting into rat joint, we have evaluated a strategy of gene transfer by means of the delivery of external electric pulses (EP) to the knee after intra-articular injection of a reporter gene (GFP). Rats were killed at various times after the electro gene-therapy to analyze GFP gene expression by immunohistochemistry. GFP staining was detected in the superficial, middle, and deep zones of the patellar cartilage at days 2 and 9, and thereafter only in the deep zone (months 1 and 2). The average percentage of GFP-positive cells was estimated at 30% both one and 2 months after the gene transfer. Moreover, no pathologic change caused by the EP was detected in the cartilage. The level and stability of the long-term GFP expression found in this study demonstrate the feasibility of a treatment of joint disorders (inflammatory or degenerative, focal or diffuse) using electric gene transfer.

Animals↗
PubMed2002

Mutations in ANKH cause chondrocalcinosis.

Chondrocalcinosis (CC) is a common cause of joint pain and arthritis that is caused by the deposition of calcium-containing crystals within articular cartilage. Although most cases are sporadic, rare familial forms have been linked to human chromosomes 8 (CCAL1) or 5p (CCAL2) (Baldwin et al. 1995; Hughes et al. 1995; Andrew et al. 1999). Here, we show that two previously described families with CCAL2 have mutations in the human homolog of the mouse progressive ankylosis gene (ANKH). One of the human mutations results in the substitution of a highly conserved amino acid residue within a predicted transmembrane segment. The other creates a new ATG start site that adds four additional residues to the ANKH protein. Both mutations segregate completely with disease status and are not found in control subjects. In addition, 1 of 95 U.K. patients with sporadic CC showed a deletion of a single codon in the ANKH gene. The same change was found in a sister who had bilateral knee replacement for osteoarthritis. Each of the three human mutations was reconstructed in a full-length ANK expression construct previously shown to regulate pyrophosphate levels in cultured cells in vitro. All three of the human mutations showed significantly more activity than a previously described nonsense mutation that causes severe hydroxyapatite mineral deposition and widespread joint ankylosis in mice. These results suggest that small sequence changes in ANKH are one cause of CC and joint disease in humans. Increased ANK activity may explain the different types of crystals commonly deposited in human CCAL2 families and mutant mice and may provide a useful pharmacological target for treating some forms of human CC.

Cells, Cultured↗
PubMed2002

The biochemical content of articular cartilage: an original MRI approach.

The MR aspect of articular cartilage, that reflects the interactions between protons and macromolecular constituents, is affected by the intrinsic tissue structure (water content, the content of matrix constituents, collagen network organization), imager characteristics, and acquisition parameters. On the T1-weighted sequences, the bovine articular cartilage appears as an homogeneous tissue in high signal intensity, whatever the age of animals considered, whereas on the T2-weighted sequences, the articular bovine cartilage presents variations of its imaging pattern (laminar appearance) well correlated to the variations of its histological and biochemical structure. The T2 relaxation time measurement (T2 mapping), which reflects quantitatively the signal intensity variations observed on T2 weighted sequences, is a way to evaluate more precisely the modifications of cartilage structure during the aging and maturation processes (rat's study). This technique so far confined to experimental micro-imagers is now developed on clinical imagers. Consequently, it may permit to depict the early stages of osteoarthritic disease (OA) or to evaluate the chondroprotective effect of drugs.

Aging↗