PubMed Health⌕ Search

Biomedical subjects

L Philippe

Publications and source records attributed to L Philippe.

At least 19 recordsLinked to original sources

Neurophysiological basis for neurogenic-mediated articular cartilage anabolism alteration.

This study was designed to investigate the pathways involved in neurogenic-mediated articular cartilage damage triggered by a nonsystemic distant subcutaneous or intra-articular inflammation. The cartilage damage was assessed 24 h after subcutaneous or intra-articular complete Freund's adjuvant (CFA) injection measuring patellar proteoglycan (PG) synthesis (ex vivo [Na(2)(35)SO(4)] incorporation) in 96 Wistar rats. Unilateral subcutaneous or intra-articular injection of CFA induced significant decrease (25-29%) in PG synthesis in both patellae. Chronic administration of capsaicin (50 mg. kg(-1). day(-1) during 4 days), which blunted the normal response of C fiber stimulation, prevented the bilateral significant decrease in cartilage synthesis. Similarly, intrathecal injection of MK-801 (10 nmol/day during 5 days), which blocked the glutamatergic synaptic transmission at the dorsal horn of signal originating in primary afferent C fibers, eliminated the CFA-induced PG synthesis decrease in both patellae. Chemical sympathectomy, induced by guanethidine (12.5 mg. kg(-1). day(-1) during 6 wk), also prevented PG synthesis alteration. Finally, compression of the spinal cord at the T3-T5 level had a similar protective effect on the reduction of [Na(2)(35)SO(4)] incorporation. It is concluded that the signal that triggers articular cartilage synthesis damage induced by a distant local inflammation 1) is transmitted through the afferent C fibers, 2) makes glutamatergic synaptic connections with the preganglionic neurons of the sympathetic system, and 3) involves spinal and supraspinal pathways.

Afferent Pathways↗

Evidence for neurogenic transmission inducing degenerative cartilage damage distant from local inflammation.

OBJECTIVE: To investigate involvement of the nervous system in ipsilateral and contralateral joint inflammation. METHODS: Freund's complete adjuvant (CFA; 1 mg or 1 microg) was injected unilaterally and the messages (a) from the hind paw to the ipsilateral and contralateral knees and (b) from one knee to the contralateral knee were analyzed. The degenerative impact of the local injury on distant cartilage was assessed using patellar proteoglycan synthesis as an indicator. Neurogenic mechanisms were blocked either by spinal cord compression or by injection of neurokinin 1 (NK-1) antagonist, or they were mimicked by intraarticular injection of substance P. The data were compared with those gathered in a model of systemic inflammation, characterized by fever and serum interleukin-6 production. RESULTS: After unilateral subcutaneous injection of CFA, proteoglycan anabolism decreased bilaterally. Spinal cord compression and administration of the NK-1 antagonist inhibited the response in the contralateral limb. Following 1 mg CFA subcutaneous injection, the ipsilateral response implicated both neurogenic and systemic mechanisms, whereas the nervous system alone was implicated after 1 microg subcutaneous CFA injection. The 1 microg CFA intraarticular injection induced a degenerative contralateral signal, which was abolished by spinal cord compression and by pretreatment with the NK-1 antagonist. Intraarticular injection of 1 microg CFA also induced an ipsilateral increase of anabolism, which was enhanced by spinal cord compression. Similar results were obtained after intraarticular injections of substance P. These effects were not reproduced with turpentine treatment, a systemic model, in which spinal cord compression had no effect. CONCLUSION: A unilateral inflammation can induce, by neurogenic mechanisms, distal bilateral degeneration of articular cartilage, implicating involvement of neuropeptides.

Animals↗

Biotelemetry: an original approach to experimental models of inflammation.

Biotelemetry is a new biological technology which evaluates continuous spontaneous locomotor activity and body temperature in rodents. The telemetry system comprises a transmitter implanted in the peritoneal cavity of the rodent, and a receiver placed beneath the animal's cage. The receiver detects the radio waves and the activity of the rodents as counts which are registered in the computer system, and the adapter detects the calibrated body temperature. First, we showed that biotelemetric studies of different species (rats, guinea pigs, mice and gerbils) provide substantial information about their circadian rhythms. Second, using the most common examples employed in pharmacology of inflammation (hyperthermia, arthritis, ischemia-reperfusion and so on) biotelemetry has helped us to clarify the pathophysiological significance of the parameters of temperature and mobility in several experimental models in rodents.

Animals↗

Diagnosis of arrhythmogenic right ventricular cardiomyopathy by fourier analysis of gated blood pool single-photon emission tomography.

To evaluate the diagnostic performance of Fourier phase analysis of gated blood pool single-photon emission computed tomography (GBP SPECT) in arrhythmogenic right ventricular (RV) cardiomyopathy, 18 patients with confirmed arrhythmogenic RV cardiomyopathy underwent GBP SPECT and x-ray cineangiography. Results were compared with data obtained with GBP SPECT in 10 control subjects. This 3-dimensional method demonstrated good correlation with cineangiography for measurements of RV enlargement and extent of the disease; RV and left ventricular segments were analyzed with the same accuracy. Tomographic abnormalities were significant decreased RV ejection fraction, RV dilatation, nonsynchronized contraction of the ventricles, increased RV contraction dispersion, presence of segmental RV wall motion disorders and/or phase delays, and occasionally regional left ventricular abnormalities. RV-delayed phase areas were always present in our population. A scoring system with RV criteria was proposed to diagnose RV disease. Because Fourier analysis of GBP SPECT provides ventricular morphologic information for the right ventricle with the same accuracy as for the left ventricle, it may replace planar radionuclide studies. Therefore, this method is helpful in patients with a strong clinical suspicion of arrhythmogenic RV cardiomyopathy, and should be used as a screening method before right ventriculography.

Adolescent↗

Mono-iodoacetate-induced experimental osteoarthritis: a dose-response study of loss of mobility, morphology, and biochemistry.

OBJECTIVE: To characterize the dose-responsiveness of morphologic and biochemical chondral changes relative to mobility in mono-iodoacetate (MIA)-induced osteoarthritis (OA) in rats. METHODS: Rat mobility was assessed by biotelemetry. Articular lesions were characterized by macroscopic and histologic examinations. Cartilage proteoglycan metabolism was evaluated by the 1,9-dimethylmethylene blue dye binding assay and by radiosulfate incorporation in patellar cartilage. RESULTS: Spontaneous locomotor activity was rapidly, transiently, and dose-dependently decreased after MIA injection into rat knees (primary response). Thereafter, only high doses (0.3 mg and 3.0 mg) led to a secondary progressive long-term loss of spontaneous mobility on day 15, when subchondral bone was exposed. These 2 doses resulted in significant changes in cartilage proteoglycan concentration at day 15 and a strong inhibition of anabolism in the peripheral patellae by day 2, contrasting with the effects of lower doses (0.01, 0.03, and 0.1 mg). CONCLUSION: When a sufficient dose of MIA is used, this model can easily and quickly reproduce OA-like lesions and functional impairment in rats, similar to that observed in human disease. These parameters, as well as proteoglycan metabolism, could serve as indicators for studying chondroprotective drugs, or for evaluating the ability of imaging techniques to detect and evaluate chondral lesions.

Animals↗

The pregnant ewe: an animal model for fetoscopic surgery.

OBJECTIVE: To develop an animal model for fetal endoscopic surgery which could be feasible and reproducible. The aim of this work was to perform a fetoscopy without the need of a laparotomy. METHODS: Pregnant ewes underwent under general anesthesia laparoscopy with the creation of a maternal pneumoperitoneum. After localizing the placenta by transillumination, we carried out fetoscopy through a 5 mm trocar using a perfusion of Ringer's solution. RESULTS: Five video-assisted procedures have been performed. None of the cases has shown any bleeding from myometrial wounds and no suture was necessary. There was no leakage of amniotic fluid. Intrauterine space was large enough to manipulate instruments without producing any fetal damage. Sharp visualization and anatomical description of the fetus were precise without the use CO2. There were no miscarriages and postnatal examinations of the lambs were normal. CONCLUSION: Fetoscopic surgery can be performed in the pregnant sheep without any complications but preterm labor which is the main problem in human fetal surgery, is infrequent in the sheep. Our model is reproducible and simulates the surgical endoscopic procedures which will occur in a close future in the human species.

Animals↗

Metastatic follicular thyroid carcinoma to the paranasal sinuses: a case report and review.

Thyroid carcinoma metastatic to the paranasal sinuses is extremely rare, with only 11 cases reported in the English and European literature. We report a case of metastatic follicular thyroid carcinoma to the clivus with extension into the sphenoid and posterior ethmoid sinuses. Pathological diagnosis was obtained using an intranasal endoscopic biopsy. As with our patient, metastatic thyroid carcinoma may present with symptoms related to distant metastases rather than the primary lesion. Distant metastases in differentiated thyroid carcinoma portends a poor prognosis. Our case of metastatic thyroid carcinoma to the paranasal sinuses is summarized in the context of the 11 additional cases, and treatment options are discussed.

Aged↗

Relations between functional, inflammatory, and degenerative parameters during adjuvant arthritis in rats.

We assessed the time-course of adjuvant arthritis (AA) in Lewis rats, using biotelemetry to monitor the rat's spontaneous locomotor activity and body temperature, and studied the evolution of the arthritic index, circulating concentrations of inflammation-promoting cytokines, cartilage proteoglycan synthesis, and the effect of indomethacin as a cyclooxygenase inhibitor to evaluate prostaglandin (PG) contribution in AA. The injection of complete Freund's adjuvant on day 0 (D0) induced a marked, transient loss of locomotor activity (D1-D4; initial phase) and then a second phase of hypomobility peaking on D15 and thereafter irreversible (D16-D20; arthritic phase). Fever peaked first on D1 and again between D13 and D17. The primary hyperthermia was associated with increases in plasma interleukin-6 and tumor necrosis factor-alpha concentrations and seemed to be partly PG dependent. Proteoglycan synthesis inhibition in the patellar cartilage increased gradually, spreading from the injected paw to the contralateral paw. It was corrected on D20 by preventive and curative indomethacin treatments. Indomethacin also greatly relieved hypomobility during the systemic phase of AA (D10-D15). The combination of information about cartilage metabolism, body temperature, locomotor activity, and cytokine in this study permits analysis of analgesic, antipyretic, anti-inflammatory, and chondroprotective properties of drugs in the various phases of AA. Thus, using a new methodology, we have discriminated the different phases of the disease and confirmed the symptomatic and systemic inhibitory effect of indomethacin on fever, activity, and cartilage metabolism.

Activity Cycles↗

[Value of tomoscintigraphy with Fourier analysis in the diagnosis of arrhythmogenic right ventricular cardiomyopathy].

ECG gated blood pool tomography has been performed in sixteen patients with right ventricular arrhythmias in whom the diagnosis of arrhythmogenic right ventricular cardiomyopathy was made based on the finding of abnormalities on contrast angiography. They were compared both to control subjects and to patients with primary dilated cardiomyopathy. Thick slices of ventricles were obtained throughout the cardiac cycle in three orthogonal planes: horizontal long axis and short axis thick slices for analysis of right and left ventricular regional wall motion abnormalities and analysis of the spread of the contraction by means of Fourier phase imaging, vertical long axis slices (one for each ventricle) for ejection fractions, because of easy and reproducible determination of valvular planes and analysis of all right ventricular segments, especially the pulmonary infundibulum. Five typical right ventricular abnormalities were seen: decreased ejection fraction (32 +/- 15% vs 55 +/- 3% in control; p < 0.001), increased diameter (ratio of right to left diameters = 1.2 +/- 0.3 vs 0.9 +/- 0.1; p < 0.01), global delayed contraction versus that of the left ventricle (22 +/- 20 degrees vs -2 +/- 6%; p < 0.01), increased dispersion of contraction (32 +/- 16 degrees vs 13 +/- 4 degrees; p < 0.01) and presence of segments with decreased and/or delayed contraction. Right ventricular disease was observed in all the patients: localized form (56%), diffused form (44%). This method provides accurate functional data for diagnosis and follow-up of patients. In future, this wall motion evaluation method may replace planar nuclear angiography as myocardial SPECT have replaced myocardial planar scintigraphy.

Adolescent↗

[A study of 36 cases of mitral valve prolapse by isotopic ventricular tomography].

Left and right ventricular wall motion was studied in mitral valve prolapse with or without ventricular arrhythmias. Regional and global ventricular wall motion was evaluated by isotopic methods, based in ejection fraction and Fourier phase analysis representing the progression of wall contraction. The synchronisation of the ventricles was characterized by the difference of the mean phase of each ventricle. The heterogeneity of contraction of each ventricle was defined by the dispersion around the mean (standard deviations of the phases). Fifteen of the 36 patients had complex ventricular arrhythmias (Lown grade > or = III). 12 had LVP and 16 had mitral regurgitation. In mitral valve prolapse, the RV EF was decreased compared with normal controls (30 +/- 9% vs 40 +/- 10% ; p < 0.001), especially in patients with mitral regurgitation (26 +/- 7% vs 30 +/- 10%; p = NS) and complex ventricular arrhythmias (26 +/- 7% vs 32 +/- 10%; p < 0.01). The SDP of the LV was greater than those of controls (18 +/- 11 degrees vs 11 +/- 5 degrees ; p = NS) whereas the SDP of the RV was greater (27 +/- 17 degrees vs 12 +/- 5 degrees ; p < 0.05) especially in those with complex ventricular arrhythmias (36 +/- 21 degrees vs 21 +/- 10 degrees : p < 0.01). The SDP of LV and RV were greater in patients with mitral regurgitation: 20 +/- 11 degrees versus 17 +/- 10 degrees (NS) and 35 +/- 21 degrees versus 20 +/- 8 degrees (p < 0.01). Heterogenous ventricular contraction, more marked in the right ventricle in mitral valve prolapse suggests severe myocardial disruption in this valvular disease, reflected by the high incidence of LVP and complex ventricular arrhythmias.

Adult↗

Small-cell carcinoma of the esophagus with regression after combination chemotherapy and radiation therapy.

The authors present an unusual case of small-cell carcinoma of the esophagus, which manifested on double-contrast esophagography as an ulcerated submucosal mass. The lesion underwent dramatic regression after combination chemotherapy and radiation therapy, which has occasionally been used as an alternative to surgery in patients with this rare but aggressive esophageal neoplasm.

Antineoplastic Combined Chemotherapy Protocols↗

[Isotopic study of myocardial perfusion and innervation in 28 patients with primary hypertrophic cardiomyopathy: relation to ventricular arrhythmia].

Ventricular arrhythmias are frequent, sometimes complex and severe, in primary hypertrophic cardiomyopathy. They carry a poor prognosis. Some workers have reported that these arrhythmias are more common in patients with abnormal myocardial perfusion. Other groups have underlined the important role of the sympathetic nervous system in the development of ventricular hypertrophy and the genesis of ventricular arrhythmias. Therefore, a population of 28 patients with primary hypertrophic cardiomyopathy (PHCM) were studied by thallium 201 myocardial scintigraphy and sympathetic innervation was assessed using a structural analogue of noradrenaline, meta-iodobenzyl-guanidine (MIBG). Then, perfusion and innervation were correlated with ventricular arrhythmias observed on 24 hours holter monitoring electrocardiogram. Perfusion abnormalities were observed in 60% of patients: stable in mild left ventricular hypertrophy, labile in severe left ventricular hypertrophy. They were not related to the presence of muscular bridges and systolic compression of septal arteries demonstrated by coronary angiography. These perfusion abnormalities were closely correlated to ventricular extrasystoles observed on Holter monitoring. In this series, and compared to controls, the fixation of MIBG as determined by the Heart/Mediastinum (H/M) ratio was significantly decreased (2.27 +/- 0.31 versus 2.57 +/- 0.33 in controls). Uniform myocardial uptake of MIBG with no defect or significant global hypofixation was observed in 32% of PHCM. Regional and occasionally global hypofixation was observed in 68% of patients. In moderate hypertrophy, reduced uptake was not uniform, the lateral wall and apex being the most abnormal. Uptake of MIBG was significantly correlated to septal wall thickness and to left ventricular mass index. These defects were related to abnormal neuronal uptake of MIBG.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

Inhibition of neurogenic inflammation in the meninges by a non-peptide NK1 receptor antagonist, RP 67580.

RP 67580, a non-peptide NK1 receptor antagonist, inhibited in a stereoselective and dose-dependent manner plasma extravasation caused in the dura mater by intravenous injection of capsaicin in guinea-pigs and of exogenous substance P in rats (ED50 = 35 and 2.5 micrograms/kg i.v., respectively). In the two species, RP 67580 appeared to be more effective in the dura mater than in the peripheral organs. These results indicate that selective NK1 receptor antagonists could be potentially effective for the treatment of migraine headache.

Animals↗

Non-invasive identification of severe coronary artery disease in patients with long-standing diabetes mellitus.

OBJECTIVES: To detect severe coronary artery disease in asymptomatic middle-aged diabetic patients exposed to coronary artery disease risk factors. PATIENTS AND METHODS: Forty-four middle-aged patients (30 to 65 years of age) with a known duration of diabetes exceeding 10 years and at least one additional cardiovascular risk factor were studied. Patients were free of anginal chest pain and had a normal 12-lead ECG at rest. All patients underwent 24-hour ambulatory ECG, maximal bicycle exercise electrocardiography and intravenous dipyridamole thallium myocardial scintigraphy. If one of these 3 non-invasive tests revealed signs of myocardial ischaemia, a coronary angiography was performed. RESULTS: Non-invasive investigation yielded the diagnosis of myocardial ischaemia in 9/44 patients (20%). Six of the 9 patients had significant coronary artery stenoses (> 70% narrowing) and 5 exhibited severe triple-vessel disease. With dipyridamole thallium scintigraphy, the positive predictive value for diagnosis of coronary artery disease was optimal. CONCLUSION: In diabetic patients with additional coronary risk factors, periodical thorough clinical examination and resting ECG may fail to detect severe coronary disease. More sophisticated cardiovascular non-invasive tests should then be proposed as part of the periodical care of these patients.

Coronary Angiography↗

Localized peripheral calcium oxalate crystal deposition caused by Aspergillus niger infection.

A 70-year-old white man, who was malnourished and demented, presented with a painful black, gangrenous-appearing right foot with a fungating mass and required amputation. Pathological sections of the tissue specimens showed numerous birefringent crystals, which were identified as calcium oxalate. Branching septate hyphae and darkly pigmented fungal fruiting heads with double sterigmata characteristic of Aspergillus niger were also identified in the tissue sections. No systemic or other metabolic causes of oxalosis were found. The calcium oxalate crystal deposition was felt to be secondary to Aspergillus niger infection.

Aged↗