PubMed Health⌕ Search

Biomedical subjects

F Debiais

Publications and source records attributed to F Debiais.

At least 19 recordsLinked to original sources

Fibroblast growth factor-2 (FGF-2) increases N-cadherin expression through protein kinase C and Src-kinase pathways in human calvaria osteoblasts.

Fibroblast growth factors (FGFs) are important factors regulating osteogenesis. However, the early mechanisms and signaling pathways involved in FGF actions in osteoblasts are unknown. We investigated the effects of FGF-2 on cell-cell adhesion and cadherin expression and the underlying signaling pathways in immortalized human neonatal calvaria (IHNC) cells. These cells express E- and N-cadherins, as shown by immunocytochemical and Western blot analyses. rhFGF-2 increased cell-cell adhesion at 24-72 h, as measured in a cell aggregation assay, and this effect was blocked by specific neutralizing anti-N-cadherin, but not anti-E-cadherin antibodies. Accordingly, ELISA and Western blot analyses showed that rhFGF-2 (10-100 ng/ml) dose dependently increased N-cadherin but not E-cadherin protein levels. RT-PCR analysis showed that rhFGF-2 transiently increased N-cadherin mRNA levels in IHNC cells. The RNA polymerase II inhibitor 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole prevented the rhFGF-2-induced up-regulation of N-cadherin mRNA, suggesting that transcription is necessary for this effect. Analysis of signaling molecules showed evidence that PLCgamma-PKC, Src, Erk 1/2 and p38 MAPK pathways are activated by rhFGF-2 in IHNC cells. The selective PKC inhibitors calphostin C, Ro-31-8220, Gö6976 and Gö6983 abrogated the stimulatory effect of rhFGF-2 on N-cadherin mRNA levels. The src-family tyrosine kinase inhibitor PP1 also blocked rhFGF-2-promoted N-cadherin expression. In contrast, the p38 MAP kinase inhibitor SB 203580 or the MEK inhibitor PD98059 had no effect on rhFGF-2-induced N-cadherin mRNA levels. Our data indicate that FGF-2 increases N-cadherin expression and function in human calvaria osteoblasts via activation of PKC and src-kinase pathways. This study identifies N-cadherin as a previously unrecognized target gene for FGF-2 signaling pathway that regulates cell-cell adhesion in human osteoblasts.

Cadherins↗

[Schwannoma of the obturator nerve with urologic manifestations: report of a case].

Peripheral nerve tumors, which are called schwannomas because they arise from nerve sheath Schwann cells, are rare tumors than can develop at any site in the body but involve the limbs in over 50% of cases. Only 13% of schwannomas arise in the trunk; about 3% of schwannomas are retroperitoneal, and about 4% of retroperitoneal tumors are schwannomas. Pelvic schwannomas are equally uncommon and can develop in a broad range of structures. The most common presenting manifestation is a very large space-occupying lesion responsible for compression of neighboring organs. Excision of the tumor is often extremely difficult or impossible. Although obturator nerve schwannomas are exceedingly rare, their paravesical location is suggestive of he diagnosis. Computed tomography and magnetic resonance imaging are the most useful investigations, although they cannot determine the exact nature of the tumor. During surgery, every effort should be made to preserve the integrity of the nerve, although this is not always possible; obturator nerve injury does not seem associated with severe impairments.

Humans↗

Femoral neuropathy secondary to ossification of the ligamentum flavum.

Radiculopathy resulting from ossification of the ligamentum flavum (OLF) is extremely rare and concerns only intercostal neuralgias. We describe a 37-year-old Caucasian woman with a lumbar radiculopathy revealing an OLF. Her symptoms were completely and definitively relieved by surgery.

Adult↗

New factors controlling bone remodeling.

Two factors of crucial importance in bone cell differentiation were discovered within the last two years. One is the transcription factor Osf2/Cbfa1, which allows mesenchymal stem cells to differentiate into osteoblasts. Soluble factors, including bone morphogenetic proteins (BMPs), leptin, and TGF-beta, can modulate differentiation of mesenchymal stem cells to osteoblasts or to other cell types such as chondrocytes or adipocytes. The other recent discovery is osteoclast differentiating factor (ODF), which is specific for and indispensable to osteoclast differentiation. ODF belongs to the TNF family. Its soluble receptor, osteoprotegerin, prevents it from binding to osteoclasts, thus inhibiting its activity. A role of lymphocytes in bone remodeling has long been suspected, and it has now been shown that ODF is produced by activated T lymphocytes, which may therefore be implicated in bone loss accompanying inflammation. Finally, recent evidence supports a role for B lymphocytes in bone loss secondary to estrogen deprivation. In conclusion, these recent data may have important applications. Osteoprotegerin is a potent antiosteoclast agent that may prove useful in the treatment of bone disorders. Osf2/Cbfa1 and ODF are major targets in the treatment of osteoporosis.

Animals↗

[Schwannoma and the urinary tract. Concerning a tumor of the obdurator nerve].

Peripheral nerve tumours, called schwannomas, because they are derived from cells of the Schwann sheath, are rare tumours that can involve any part of the body, but are essentially located on the limbs, which represent more than 50% of cases. Schwannomas of the trunk and especially pelvic schwannomas are even rarer. A tumour arising from the obturator nerve is exceptional, but its paravesical location can facilitate the diagnosis, as in this case. The complementary investigations most frequently performed are CT and MRI, although they are unable to define the exact nature of the tumour. Surgery must try to preserve continuity of the nerve, but that is not always possible and does not appear to have any major consequences in this site.

Humans↗

The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic cells are differentiation stage specific.

Fibroblast growth factors (FGFs) appear to play an important role in human cranial osteogenesis. We therefore investigated the effects of recombinant human FGF-2 (rhFGF-2) on human calvaria (HC) osteoblastic cells. Immunocytochemical analysis showed that confluent HC cells express both FGF receptors -1 and -2. In short-term culture, rhFGF-2 (0.1-100 ng/ml, 2-5 days) increased HC cell growth and decreased alkaline phosphatase (ALP) activity and type I collagen (ColI) synthesis, as evaluated by P1CP levels. When HC cells were induced to differentiate in long-term culture in the presence of 50 microg/ml ascorbic acid and 3 mM phosphate, HC cells initially proliferated, then ALP activity and ColI synthesis decreased and calcium content in the extracellular matrix increased. Continuous treatment with rhFGF-2 (50 ng/ml) for 1-28 days, or a transient rhFGF-2 treatment for 1-7 days, slightly increased DNA synthesis at 7 days, whereas a late treatment for 8-28 days had no effect on cell growth. The continuous and transient treatments with rhFGF-2 decreased ALP activity, ColI synthesis, and matrix mineralization. This was associated with a transient fall in osteocalcin (OC) production at 7 days. In contrast, the late rhFGF-2 treatment for 8-28 days only slightly inhibited ALP activity and increased matrix mineralization. In addition, both continuous and late treatments with rhFGF-2 increased OC production in more mature cells at 3-4 weeks of culture. We also found that the early and late treatments with rhFGF-2 had opposite effects on transforming growth factor beta2 production in proliferating cells and more mature cells. The results show that rhFGF-2 slightly stimulates cell growth and reduces the expression of osteoblast markers in less mature cells, whereas it induces OC production and matrix mineralization in more mature cells, indicating that the effects of FGF-2 are differentiation stage specific and that FGF-2 may modulate HC osteogenesis by acting at distinct stages of cell maturation.

Alkaline Phosphatase↗

A randomized, double blind, placebo controlled multicenter trial of murine anti-CD4 monoclonal antibody therapy in rheumatoid arthritis.

OBJECTIVE: To assess safety and efficacy of a murine anti-CD4 monoclonal antibody (Mab) in a population of patients with rheumatoid arthritis (RA) compared to treatment with placebo. METHODS: Fifty-eight patients with defined RA were included in this placebo controlled, randomized, double blind, multicenter study. Of the 48 women and 10 men (mean age 54.5 years), 25 were functional class II and 31 were class III, with 9 years' disease duration; the mean of previous disease modifying antirheumatic drugs was 4; 49 were taking steroids (mean dosage 11 mg/day of prednisone). Eighty percent were rheumatoid factor positive. All were in an active state of the disease with: pain > 4 (mean at inclusion 6.6), tender joints > 4 (mean 12), swollen joint count > 3 (mean 9), morning stiffness > 45 min (mean 185), erythrocyte sedimentation rate > 30 mm (mean 59) or C-reactive protein (CRP) > 30 mg/l (mean 63). Treatment was randomized between murine anti-CD4 Mab (B-F5, Diaclone, 20 mg/day) or placebo intravenously for 10 consecutive days. Efficacy was assessed with a composite index (Paulus), with evaluation of number of patients with 20 or 50% improvement in each group. Changes in measures of single clinical or biological variables were also evaluated. RESULTS: The 2 groups were comparable at inclusion. Treatment was well tolerated. Mild side effects (chills, fever, rash) were seen in both groups. Percentage of patients with global 20 or 50% response did not differ between placebo and Mab groups at Day 10 or at Day 30. Evaluation of single variables showed reduced CRP, swollen joint count, and Ritchie index in some B-F5 patients at Day 10, although in the B-F5 group as a whole only CRP was significant. CONCLUSION: No significant improvement in RA after murine anti-CD4 Mab was observed.

Adult↗

Time-frequency analysis of heart murmurs. Part I: Parametric modelling and numerical simulations.

The object of this study is to compare the performance of two new bilinear time-frequency representation techniques with the spectrogram to characterise the behaviour of heart murmurs produced by bioprosthetic heart valves implanted in the mitral or aortic position. The murmurs are those of mitral stenosis, mitral regurgitation, aortic stenosis, aortic regurgitation, a diastolic musical murmur and a systolic musical murmur. In the first part of the study, the general characteristics of the amplitude and the spectral content of these murmurs are determined by visual observation of the spectrogram of phonocardiograms obtained from several patients with known valvular pathology complemented with a literature review. A parametric model is then generated for each murmur signal. Stenotic and regurgitant murmurs are modelled as the sequential output of a bank of low-pass filters excited by a white noise input signal. The basic parameters of each filter are selected to simulate, as a function of time, the basic characteristics of random heart murmurs. Musical murmurs are modelled as a frequency-modulated deterministic sinusoid of constant amplitude. Numerical simulations of these random and musical heart murmurs are then generated and will be used in Part II to determine the best of three time-frequency representation techniques for analysing heart murmur signals.

Aortic Valve↗

Time-frequency analysis of heart murmurs. Part II: Optimisation of time-frequency representations and performance evaluation.

The basic parameters of the spectrogram, the Choi-Williams, and the Bessel distributions are adjusted to provide the best time-frequency representations (TFRs) of the simulated murmur signals of mitral stenosis, mitral regurgitation, aortic stenosis, aortic regurgitation, and of two musical murmurs. The initial adjustment of the parameters of each TFR technique is performed by computing and minimising the relative averaged absolute error between the frequency contours at -3 dB and -10 dB of each TFR of the simulated murmurs and those of the theoretical distribution of the same signals. The results show that the spectrogram generally provides very good to excellent performance in representing the TFRs of stenotic and regurgitant murmurs. Improvements provided by the Choi-Williams and the Bessel distributions are minor but not systematic for the two signal-to-noise ratios tested (0 and 30 dB) and for the two frequency contours estimated. The Bessel and the Choi-Williams distributions provide the best performance for the musical murmurs. The study shows that although a single technique cannot be optimal for all six murmurs, the spectrogram using a Hamming window of 30 ms is an acceptable compromise to detect the six simulated heart murmurs.

Computer Simulation↗

[Are the anatomopathological classifications of primary Gougerot-Sjögren syndrome correlated with each-other and with clinical symptoms?].

Seventy-two cases of primary Sjögren's syndrome, according to the European classification criteria, were studied looking for a correlation between anatomic criteria and clinico-biological signs in this disease. Labial salivary gland biopsy was performed in all patients and anatomic criteria were evaluated according to both Chisholm and Chomette scales. Work-up included recording of functional and clinical signs. Our study shows no clinico-histological correlation in Sjögren's syndrome. Moreover, we did not find any correlation between the two histological scales. We think, therefore, that labial salivary gland biopsy appears to be an important step in Sjögren's syndrome diagnosis according to European criteria. However, it does not present any benefit in patient treatment.

Adult↗

Open synovectomy for the prevention of recurrent hemarthrosis of the ankle in patients with hemophilia. A report of five cases with magnetic resonance imaging documentation.

Hemophilic arthropathy is an incapacitating complication of severe hemophilia resulting from recurrent bleeding in the same joint. Open synovectomy has been used since 1969 to prevent recurrent hemarthrosis of target joints. Between 1988 and 1993 we performed open synovectomy of the ankle in five hemophiliacs aged 6 to 9 years with early-stage hemophilic arthropathy. Magnetic resonance imaging proved very useful for evaluating the severity of joint damage, usually underestimated on plain radiographs; for determining the degree of synovial membrane hypertrophy, which is a critical factor in the decision to perform synovectomy; for planning the surgical procedure and for explaining treatment failures. A decrease in the frequency of hemarthrosis episodes occurred in all five ankles. A repeat synovectomy was needed in one case and in another patient the frequency of hemarthrosis episodes increased somewhat after the fourth year. There was no loss of range of motion. Our data suggest that open synovectomy is effective and safe for reducing the frequency of hemarthrosis and that magnetic resonance imaging should be routinely performed before the procedure.

Ankle↗

Strategy for identifying primary malignancies with inaugural bone metastases.

The diagnosis of primary tumors with inaugural bone metastases is a serious and difficult problem commonly encountered in rheumatology. Helpful information can be derived from the radiologic appearance of the metastases, history of the patient, clinical findings, chest film, standard laboratory tests, imaging studies, serum marker assays, and histologic findings. Based on our personal experience and on previously published data, we have developed a decision tree aimed at enhancing the efficacy of the diagnostic process while ensuring optimal patient comfort and containing costs.

Adult↗

[Lyme disease].

Lyme disease is an infectious disease due to Borrelia burgdorferi, which is transmitted by a tick bite. Bearing ticks belong to the "Ixodes" type. Germ reservoirs include rodents, birds, deers... The disease onset usually takes place in summer or in autumn. Its early stage is characterized by erythema chronicum migrans. The secondary stage, initiated by a virus-like syndrome indicating the hematogenous and lymphatic dissemination may include neurologic symptoms and signs--the most frequent ones in France and Europe (meningoradiculitis, meningitis, palsy of one or several cranial nerves), cardiac symptoms (conduction dysfunction), a relapsing oligoarthritis, and sometimes ocular signs. In some cases, joint and/or nervous system symptoms may become chronic: it's the tertiary (late) stage, which may include, too, acrodermatitis chronica atrophicans. Any of these symptoms may initiate the disease or be its only manifestation. When erythema chronicum migrans is missing, diagnosis lays upon serology which may turn positive only lately, or remain negative; the possibility of false positivity must also be noticed. Antibiotherapy must be initiated as soon as possible; even when started lately, it may prove beneficial. It consists essentially of beta lactamins or doxycyclin. Studies are progressing in view of the elaboration of a vaccine.

Anti-Bacterial Agents↗

[Treatment of Takayasu's disease with low-dose methotrexate. Apropos of a case].

Persistent evidence of inflammation at the occlusive phase of Takayasu's arteritis is of adverse prognostic significance. Low-dose weekly methotrexate therapy given in combination with a corticosteroid may be effective in such patients. We report a personal case which supports the data obtained by Fauci and coworkers, as well as the conclusions of the other two similar case-reports in the literature.

Drug Therapy, Combination↗

[Chemonucleolysis of disk herniation with low back pain as the single symptom: 20 cases].

Disk herniation can manifest as isolated low back pain, which is usually intermittent and accompanied with stiffness of the lumbar spine. There is almost general agreement that neither neurosurgical treatment nor chemonucleolysis is appropriate in patients with this clinical pattern. We used chemonucleolysis in 19 patients with recurrent episodes of isolated low back pain and one patient with severe permanent isolated low back pain dating back to a conservatively-treated episode of sciatica. All 20 patients had disk herniation documented by imaging studies. A very good or satisfactory outcome was recorded in ten patients after three months, 11 after six months and 12 in March 1993 after a mean follow-up of 72 months. The treatment was well tolerated, even in those patients who were not improved; a single patient developed an episode of acute low back pain that required surgical treatment. In patients with low back pain and disk herniation, there is currently no means of determining whether a causal relationship links these two abnormalities. Nevertheless, we believe that chemonucleolysis can be proposed in severe forms, provided the patients are apprised of current success rates.

Adult↗

[Unsatisfactory results of intradiscal injection of triamcinolone hexacetonide in the treatment of sciatica caused by intervertebral disk herniation].

Sciatica caused by intervertebral disc herniation can be treated with intradiscal injection of chymopapain. A search for a cheaper and less allergizing product led to triamcinolone hexacetonide, this procedure being known as "nucleorthesis". The first results at 6 months were encouraging. In 3 centres where triamcinolone hexacetonide was tested with a more than 2 years' follow-up 92 patients could be evaluated. The results obtained were considered satisfactory in 34 patients (36.9 percent), but they were poor in 19 patients (20.6 percent), and 39 patients (42 percent) had to be operated upon within 2 years. Return to surgery took place within the 6 months following nucleorthesis in 18 patients (19.56 percent) and beyond this period in 17 patients (22.8 percent) with degradation of the results. Moreover, calcifications were found in 19 out of 38 patients; they were of varying size, sometimes detected only at computerized tomography, and some of them appeared to produce symptoms. All considered, the failure rates, the number of patients who required surgery and the occurrence of large and sometimes symptomatic calcifications make triamcinolone nucleorthesis unacceptable compared with the recognized percentages of success with papain nucleolysis and surgical operations. For these reasons, we consider that this treatment should be abandoned.

Anti-Inflammatory Agents↗

[Infectious spondylodiscitis. Analysis of a series of 105 cases].

Among 105 cases of infectious spondylitis diagnosed and treated from 1971 through 1990, 23 were due to tuberculosis (TS) and 82 to other causes (NTS). The annual number of cases of NTS rose over the study period, partly because of an increase in iatrogenic spondylitis, whereas the number of TS cases fell. In both groups, mean age of patients was higher than in earlier studies. The leading causative agents in NTS were staphylococci, followed by streptococci, then Escherichia coli. Diagnosis of spondylitis was dependent on the imaging techniques used; among available methods, the most reliable was magnetic resonance imaging which improved diagnostic performance by detecting early, specific changes. Except in patients with positive blood cultures and in TS patients with Koch bacilli recovered from other visceral foci, bacteriologic diagnosis rested on studies of samples taken from the spinal infection site. Half the subjects underwent discovertebral needle biopsy, with a success rate of 47.5%, a figure comparable with those reported in other studies. In 30% of patients, bacteriologic documentation of the infection was not obtained and diagnosis rested on a set of clinical, biological, and radiological criteria.

Bacterial Infections↗

[Calcifications after intra-disk injection of triamcinolone hexacetonide in lumbar disk hernia. Evaluation of therapeutical results in 3 years].

The development of disk or epidural calcifications is a frequent possibility following intra-disk injection of triamcinolone hexacetonide. It was found 10 times in 26 follow-up CT scans obtained 2 to 3 years after the injection. These calcifications are often clinically silent, but they sometimes accompany a recurrence of the initial painful symptomatology. Furthermore, evaluation at 3 years of therapeutic results in a previously published series of patients who had received an intra-disk injection of triamcinolone hexacetonide showed a marked decrease in favourable results (30% vs 67% at 6 months). These two arguments: disappointing long term results and possibility of disk calcifications, are felt by the authors to justify abandoning the technique of triamcinolone hexacetonide by intra-disk injection in the treatment of lumbar disk prolapse.

Adult↗