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Denis Mulleman

Publications and source records attributed to Denis Mulleman.

13 recordsLinked to original sources

An enzyme-linked immunosorbent assay for therapeutic drug monitoring of infliximab.

An enzyme-linked immunosorbent assay (ELISA) measuring serum infliximab concentrations in treated patients was developed. Microtiter plates were sensitized with tumor necrosis factor alpha (TNF-alpha) and saturated with phosphate-buffered saline (PBS) containing 1% bovine serum albumin (BSA). Samples diluted 1:100 in PBS-1% BSA were added and bound infliximab was detected using peroxidase-conjugated goat anti-human immunoglobulin G specific for Fc fragment (HRP-anti hIgG). Reading was performed using an ELISA plate reader. The limit of detection, calculated by assaying 10 replicates of a drug-free serum sample or blank sample and defined as the lowest concentration distinguishable from zero at 2 standard deviations, was 0.014 microg/mL. Each quality control sample was tested on 7 occasions on 1 day and on 5 separate days. The intraday precision indices of the method were (percent coefficients of variation, CV%) 11.7%, 6.2%, and 6.9% for 0.04 microg/mL, 2 microg/mL, and 4.5 microg/mL, respectively. The corresponding bias measures (percent deviation) were -5.5%, -1.9%, and -7.9%, respectively. The between-days precision was 9.8%, 5.3%, and 5.3% for 0.04 microg/mL, 2 microg/mL, and 4.5 microg/mL, respectively. The corresponding bias were +0.3%, -0.3%, and -7.8%, respectively. Lower limit of quantitation and upper limit of quantitation were 0.04 microg/mL and 4.5 microg/mL, respectively. Trough serum concentrations of infliximab were measured in 6 adult patients with various diseases and in 5 pediatric patients with Crohn's disease. For the latter group, samples drawn 1 hour after the end of the infusion and repeated measurements also were available. Data were described using a 1-compartment population pharmacokinetic model. Terminal elimination half-life was 10.9 days. This method is rapid, accurate, and reproducible, and may be useful in therapeutic drug monitoring of infliximab.

Adolescent↗

Streptococcal and enterococcal spondylodiscitis (vertebral osteomyelitis). High incidence of infective endocarditis in 50 cases.

OBJECTIVE: To characterize the clinical, biological, and imaging features and outcomes of patients with streptococcal and enterococcal spondylodiscitis (SESD). METHODS: This retrospective study of patients with SESD was carried out in 2 departments of rheumatology from 1990 through 2002. Comparison was made with cases of staphylococcal spondylodiscitis (SSD) seen during the same period, excluding postoperative cases. RESULTS: Fifty cases of SESD were reviewed and compared with 86 cases of SSD. The main finding was a higher frequency of concomitant infective endocarditis in patients with SESD (11/42 vs 1/37; p = 0.009). Evidence of inflammation, imaging features, and neurological impairment at admission appeared to be less severe in SESD, but the difference did not reach statistical significance. Duration of treatment was shorter in SESD than in SSD (105 +/- 26 days vs 130 +/- 49 days; p = 0.003). CONCLUSION: Our study confirms the high incidence of infective endocarditis (26%) during SESD. Clinicians must look for predisposing factors and clinical abnormalities in patients with spondylodiscitis whenever a streptococcal or enterococcal agent is identified. Echocardiography should be performed as routine in such situations.

Adolescent↗

Characteristics of patients with spinal tuberculosis in a French teaching hospital.

OBJECTIVE: To investigate the characteristics of patients managed for spinal tuberculosis at the rheumatology department of the Tours Teaching Hospital, France, between 1986 and 2003. METHODS: Retrospective chart review. The incidence, epidemiology, clinical features, imaging study findings, and diagnostic procedures were recorded. RESULTS: The annual incidence of spinal tuberculosis was stable throughout the study period. There were 24 patients, 15 women and nine men with a mean age of 61 years; 15 patients were of French descent, three were of Portuguese descent, two were Asian, and four were North-African. Risk factors consisted of alcohol abuse in one patient, diabetes in two patients, glucocorticoid therapy in two patients, and a history of tuberculosis in six patients; none of the patients had AIDS. The cervical spine was involved in two patients, the thoracic spine in 11 patients, and the lumbar spine in 12 patients. Mean time from symptom onset to diagnosis was 4.3 months (range, 1-12 months). Percutaneous vertebral biopsy established the diagnosis in 16 of the 20 patients who underwent this procedure. CONCLUSION: The annual incidence of spinal tuberculosis remained unchanged throughout the study period and was not influenced by immigration or the AIDS epidemic. The typical patient was an elderly Caucasian woman of French descent. Reactivation of untreated or inadequately treated tuberculosis was probably the main mechanism.

Aged↗

Is epidural lipomatosis associated with abnormality of body fat distribution? A case report.

CASE REPORT: To report a case of epidural lipomatosis in a patient with abnormal adipose tissue distribution, glucose intolerance and mixed hyperlipidemia. A 63-year-old male patient presented with low back pain radiating to the left calf on standing and walking (walking distance <100 m). He weighed 97.5 kg, was 1.73 m tall (BMI 32.6 kg/m2) and had a waist circumference of 113 cm. He had a glucose intolerance after a 75-g glucose oral load test. CT-Myelography revealed voluminous epidural lipomatosis around L4-L5 and L5-S1. Low calorie diet and reduction in alcohol intake achieved a weight loss of 17.5 kg in 7 months (80 kg, BMI 25.8 kg/m2, waist circumference 94 cm) and dramatic improvement in low back pain, walking distance (>500 m) and reduction of lipomatosis on CT-scan. Our case suggests a relationship between central obesity phenotype and epidural lipomatosis. Specific insulin resistance treatment might be proposed for these patients if this hypothesis is confirmed in further studies.

Body Fat Distribution↗

Pathophysiology of disk-related sciatica. I.--Evidence supporting a chemical component.

Sciatica in patients with disk disease was long ascribed to pressure put on the sciatic nerve root by a herniated disk. However, a role for chemical factors acting in conjunction with this mechanical insult is suggested by a number of clinical observations: disk surgery does not consistently provide pain relief, large disk herniations are not always symptomatic, severe pain may be present in patients without imaging evidence of nerve root compression, the severity of symptoms and neurological signs is not well correlated with the size of the disk herniation, and conservative therapy is often effective. Experimental studies have provided further evidence for a chemical component: disk herniations can undergo spontaneous resorption, the intervertebral disk is immunogenic, and mediators for inflammation have been identified within intervertebral disk tissue. The current pathophysiological theory incriminates proinflammatory substances secreted by the nucleus pulposus (NP). When preexisting or concomitant mechanical injury to a nerve root occurs, these substances can cause nerve root pain. Animal experiments have established that the NP can induce functional and structural nerve root abnormalities in the absence of mechanical compression and that this effect is mediated by substances located at the surface of NP cells. Methylprednisolone, diclofenac, indomethacin, doxycycline, and cyclosporine induce variable inhibition of this effect. Available information points to tumor necrosis factor-alpha (TNF-alpha) as the main candidate among substances potentially responsible for nerve root pain. Therefore, trials of TNF-alpha antagonists in patients with disk-related sciatica are warranted.

Animals↗

Pathophysiology of disk-related low back pain and sciatica. II. Evidence supporting treatment with TNF-alpha antagonists.

Strong evidence suggests that TNF-alpha may be among the chemical factors involved in disk-related sciatica. TNF-alpha is involved in the genesis of nerve pain in animal models and may promote pain-signal production from nerve roots previously subjected to mechanical deformation. In animal experiments, TNF-alpha has been identified in nucleus pulposus and Schwann cells. Local production of endogenous TNF-alpha may occur early in the pathogenic process. Exposure to exogenous TNF-alpha induces electrophysiological, histological, and behavioral changes similar to those seen after exposure to nucleus pulposus, and these changes are more severe when mechanical compression is applied concomitantly. TNF-alpha antagonists diminish or abolish abnormalities in animal models. Other cytokines may be involved also, as suggested by the potent inhibitory effects of compounds such as doxycycline. Two open-label studies in humans suggest dramatic efficacy of TNF-alpha antagonists in alleviating disk-related sciatica. In contrast, the results of the only controlled study available to date do not support a therapeutic effect of TNF-alpha antagonists. Thus, whether TNF-alpha antagonist therapy is warranted in patients with disk-related sciatica remains an open question, and further randomized controlled studies are needed.

Animals↗

Ossification of the posterior longitudinal ligament of the cervical spine and SAPHO syndrome.

We describe a case of cervical cord compression due to ossification of the posterior longitudinal ligament of the spine (OPLLS) in a 43-year-old Vietnamese patient with SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, and osteitis). Idiopathic OPLLS is mainly reported in 50- to 60-year-old men, particularly in Japanese, with a prevalence of 2%. Cervical myelopathy may occur. In addition to OPLLS in patients of Asian origin, the condition has also been described in association with ossifying diseases, including ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) but not previously, to our knowledge, with SAPHO syndrome.

Acquired Hyperostosis Syndrome↗

Primary amyloidoma of the axis and acute spinal cord compression: a case report.

BACKGROUND: Localized primary amyloidosis is a disease characterized by a single tumor and localized amyloid deposit (amyloidoma) with no evidence of generalized amyloidosis. The occurrence of an amyloidoma in the spine is rare and only three cases affecting the axis have been previously reported. We describe the case of a 79-year-old woman presenting with a mass involving the odontoid process, responsible for an acute tetraparesia. Diagnosis of local primary amyloidosis was made after surgical excision. RESULTS: Despite the critical presentation, outcome was excellent after total excision of the mass. This case can be classified as a primary localized amyloidoma. The patient did not exhibit any infection, tumor or inflammatory disease, and continued investigations failed to demonstrate other amyloid deposit after one-year follow-up. CONCLUSIONS: Amyloidoma must be discussed in presence of a tumor-like mass of the odontoid process and may be responsible, as in our case, for spinal cord compression.

Aged↗

Multiple myeloma presenting with widespread osteosclerotic lesions.

Sclerotic lesions are rare in malignant monoclonal gammopathies, although they are occasionally associated with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes). In most cases, osseous lesions in POEMS syndrome present as an isolated sclerotic deposit or a combination of both lytic and sclerotic lesions. Diffuse osteosclerosis is extremely rare and may lead to the diagnosis of multiple myeloma, classically known to present as lytic lesions in the skeleton, with or without diffuse osteoporosis. We report a 74-year-old woman with widespread and substantial osteosclerotic lesions, associated with IgA-lambda myeloma, and with no other criteria for POEMS syndrome, and who was rapidly diagnosed with compression of the spinal cord. Detailed knowledge of imaging features in myeloma emphasises the need to consider plasma cell neoplasm in the differential diagnosis of any pattern of bone sclerosis. Although exceptional, multiple myeloma must be borne in mind in the presence of diffuse bone sclerosis.

Aged↗