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Biomedical subjects

S Perrot

Publications and source records attributed to S Perrot.

At least 19 recordsLinked to original sources

[Cytotoxicity evaluation of different eyes drops with cyclosporine oral solution (Sandimmun)].

INTRODUCTION: Cyclosporine is a molecule used in ophthalmology for the prevention of corneal graft rejection. The systemic use of this product can lead to serious adverse side effects that can be avoided using the topical formulation of cyclosporine. However, cyclosporine application can induce ocular irritation. MATERIAL AND METHODS: The aim of this study is to evaluate the cytotoxicity of four formulations of 2% cyclosporine eye drops: Sandimmum intravenous solution diluted with NaCl 0.9%, Sandimmun oral solution diluted in castor oil or corn oil after ethanol evaporation, and Sandimmun oral solution diluted in castor oil without previous ethanol evaporation. Two tests--the Draize test and the evaluation of cytotoxicity of adherent alive cells with cold light cytofluorimetry on microplates--were used in this study. RESULTS: These tests demonstrated that the aqueous solution shows more toxicity than the other formulations, and the type of oil and ethanol concentration influence cell viability. CONCLUSION: These results helped the Pharmacy unit choose the vehicles for a safe cyclosporine eye drop formulation and thus decrease the side effects of cyclosporine eye drop instillation with a decrease in ethanol concentration compared to published formulations.

Administration, Oral↗

Management of a patient with sarcoid calcaneitis and dactylitis.

Dactylitis and calcaneitis developed in a patient with untreated sarcoidosis of the skin and lungs. Radiographs showed a defect in the second phalanx of the left middle finger. Radiographs of the feet were normal, but magnetic resonance imaging demonstrated a defect in the left calcaneus. Methylprednisolone therapy (1 g per day for 3 consecutive days) induced a dramatic improvement within 48 hours. Low-dose oral glucocorticoid therapy was given subsequently. One year later, a recurrent episode of dactylitis responded promptly to the same regimen. Maintenance therapy was given, and no further recurrences were noted during the four-year follow-up. Sarcoid bone lesions are uncommon and arise selectively in the small bones of the hands and feet. Involvement of the calcaneus is exceedingly rare, and its treatment is not standardized. In our patient, glucocorticoid therapy combined with methotrexate and hydroxychloroquine were effective in controlling the disease.

Adult↗

Differential behavioral effects of peripheral and systemic morphine and naloxone in a rat model of repeated acute inflammation.

BACKGROUND: It has been reported that opioid antinociceptive effects are enhanced in animal models of inflammation, but it remains unclear whether this sensitization to morphine is related to predominant central or peripheral increased effects. METHODS: The authors compared the behavioral effects of intraplantar and intravenous morphine and naloxone in a rat model of repeated acute carrageenan-induced inflammation in which enhanced responses to noxious stimuli result from sensitization in peripheral tissues or central sensitization. The antinociceptive effects of intraplantar morphine (50, 75, 100, 150, and 200 microg), intravenous morphine (0.3, 0.6, and 1 mg/kg), and the pronociceptive effects of intraplantar naloxone methiodide (150 microg) and intravenous naloxone (1 mg/kg) against noxious pressure (vocalization thresholds to paw pressure) in rats were assessed 3 h after one or two carrageenan plantar injections performed 7 days apart. RESULTS: After the first carrageenan injection, intraplantar and intravenous morphine produced significant increase of vocalization thresholds to paw pressure in inflamed but not in noninflamed paws. After the second carrageenan injection, the antinociceptive effects of intraplantar morphine were significantly reduced compared with those obtained after the first carrageenan injection, whereas effects of intravenous morphine were significantly enhanced and present in both hind paws. Intravenous naloxone demonstrated similar pronociceptive patterns after the first and second carrageenan injection. Intraplantar naloxone methiodide produced pronociceptive effects in inflamed hind paw that were significantly enhanced after the second carrageenan injection. CONCLUSIONS: When inflammation is enhanced by recurrent stimulations, the antinociceptive effects of systemic morphine are enhanced. This increase is more likely related to central than peripheral sites of action, beyond endogenous opioid system activation.

Analgesics, Opioid↗

[Is anticoagulant therapy useful when treating erysipelas?].

INTRODUCTION: Low or high dosage heparin adjuvant therapy for Erysipelas (E) has become frequent, especially in France. MATERIAL AND METHODS: Publications on erysipelas complications were reviewed, and 2 studies were found in which the detection of deep venous thrombosis (DVT) was systematically performed: Mahe A (6DVT/40E), and Perrot JL (4DVP/155E). We calculated the relative incidence (CRI) at 4.9 p. 100, for all studies systematically detecting the DVT (whether symptomatic or not). The other studies reported clinical DVT. CRI was at 0.7 p. 100 without heparin adjuvant therapy. CRI was at 0, not statistically significant, with low or high dosage heparin adjuvant therapy. The most frequent complications for heparin treatment were: thrombocytopenia (5.7 and 0.9 p. 100 respectively with standard and low weight heparin), and hemorrhage (less than 3 p. 100 for DVT treatment). DISCUSSION: The risk of DVT associated with E is inferior to 10 p. 100 (the level of risk for DVT is small according to consensus conferences on thromboembolism). The incidence of asymptomatic DVT is superior to that of symptomatic DVT. But we do not know if asymptomatic DVT is equivalent to symptomatic DVT. Consensus conferences on thromboembolism do not recommend the preventive administration of heparin to bedfast patients with a low risk of DVT. CONCLUSION: There is no indication of adjuvant anticoagulant therapy for erysipelas. There is no indication for systematic prophylactic anticoagulant therapy for erysipelas. Prophylactic anticoagulant therapy is used depending on other risk factors of DVT. Wearing stockings may be another indication for patients.

Anticoagulants↗

[Factors in the chronic progression of common low back pain].

The main risk factors for developing chronic low back pain are related to comorbidity, the social circle of the patient and family status, the patient's concept of his health status, the patient's profession and the interval before medical treatment. For patients undergoing surgery, the same risk factors for chronic low back pain are found, with a predominance of professional status and age of the patient. On the contrary, the initial handicap and the type of management are of little importance in patient outcome. It is important to detect early the factors that risk to favour the transition to chronicity of low back pain. The effectiveness of both medical and socio-professional approaches to prevention remains to be evaluated and defined in prospective studies.

Adult↗

Lipopolysaccharide-activated kinase, an essential component for the induction of the antimicrobial peptide genes in Drosophila melanogaster cells.

Eukaryotic organisms use a similar Rel/NF-kappaB signaling cascade for the induction of innate immune genes. In Drosophila, lipopolysaccharide (LPS) signal-induced activation of the Rel/NF-kappaB family transcription factors is an essential step in the transcriptional activation of inducible antimicrobial peptide genes. However, the mechanism by which the LPS-induced signaling pathway proceeds remains largely unknown. Here we have cloned a novel Drosophila LPS-activated kinase (DLAK) that is structurally related to mammalian IkappaB kinases. DLAK is expressed and transiently activated in LPS-responsive Drosophila cells following LPS stimulation. Furthermore, DLAK can interact with Cactus, a Drosophila IkappaB and phosphorylate recombinant Cactus, in vitro. Overexpression of dominant-negative mutant DLAK (DLAK(K50A)) blocks LPS-induced Cactus degradation. DLAK-bound Cactus can be degraded in a LPS signal-dependent fashion, whereas the DLAK(K50A) mutant-bound Cactus is completely resistant to degradation in the presence of LPS. The DLAK(K50A) mutant also inhibits nuclear kappaB binding activity and kappaB-dependent diptericin reporter gene activity in a dose-dependent manner, but the kappaB-dependent diptericin reporter gene activity can be rescued by overexpression of wild type DLAK. Moreover, mRNA analysis of various kappaB-dependent antimicrobial peptide genes shows that LPS inducibility of these genes is greatly impaired in cells overexpressing DLAK(K50A). These results establish that DLAK is a novel LPS-activated kinase, which is an essential signaling component for the induction of antimicrobial peptide genes following LPS treatment in Drosophila cells.

Amino Acid Sequence↗

[Intrahepatic portocaval shunt: review of the literature, apropos of 1 case].

We report a case of portal-hepatic shunt which was detected fortuitously by ultrasonography in a 66-year-old patient. This abnormality, mainly described in cirrhotic liver and rarely in healthy liver, is usually revealed by hepatic encephalopathy or glycoregulation disorders. We propose a diagnostic and therapeutic approach based on a review of the literature.

Aged↗

Effects of intraplantar morphine on paw edema and pain-related behaviour in a rat model of repeated acute inflammation.

Recent studies suggest that peripheral morphine may represent a valuable treatment in inflammatory painful diseases. This study examined effects of intraplantar morphine against noxious pressure and paw edema in rats with repeated acute inflammation induced by two carrageenin injections 7 days apart. This model mimics at least partly some aspects of recurrent inflammatory pain encountered in the clinical situation. In the first part of the experiment, the effect of intraplantar morphine into the inflamed hindpaw was determined 3 h after carrageenin injection. Intraplantar morphine (50-200 microg) produced significant elevations of vocalization thresholds to paw pressure in inflamed but not in non-inflamed paws after both carrageenin injection; these effects were reversible by intraplantar naloxone methiodide (40 microg). The effects of intraplantar morphine (150 microg) were similar in magnitude to that of intravenous morphine (1 mg/kg) after first carrageenin injection. In contrast, at doses of 150-200 microg, they were significantly lower after second ipsilateral carrageenin injection 7 days later, than first injection. Intraplantar morphine (100-200 microg) had no effect on paw edema associated with both carrageenin injections. In the second part of the experiment, intraplantar morphine was injected 10 min before the first injection of carrageenin. Intraplantar morphine (50 microg) was ineffective, whereas morphine (100-200 microg) prevented reduction of vocalization thresholds to paw pressure of inflamed hindpaw for 3 h. The intraplantar injection of morphine (100 and 150 microg) produced a transient increase in the volume of inflamed hindpaw, not reversible by intraplantar naloxone methiodide (40 microg). Pretreatment with intraplantar morphine had no effect on reduction of vocalization thresholds to paw pressure and edema related to a second ipsilateral injection of carrageenin 7 days later. These findings suggest that peripheral morphine may be useful for the clinical management of acute inflammatory pain rather than in recurrent inflammatory painful situations.

Acute Disease↗

The enhancement of morphine antinociception by a CCKB receptor antagonist in the rat depends on the phase of inflammation and the intensity of carrageenin-induced hyperalgesia.

The ability of the cholecystokinin B (CCKB) receptor antagonist L-365,260 to modulate the antinociceptive action of systemic morphine was investigated using the well established rat model of localized inflammation induced by intraplantar injection of carrageenin. The effects of morphine (0.1-1 mg/kg i.v.) alone or in combination with the CCKB receptor antagonist (0.2 mg/kg s.c.) were determined at different time-points (at 1, 3 and 24 h) after the injection of carrageenin by measuring the vocalization threshold to paw pressure. L-365,260 was found to be ineffective in modulating the responses to all doses of morphine at 1 and 24 h after carrageenin. By contrast, at 3 h, the CCKB receptor antagonist reversed the ineffectiveness of the low dose (0.1 mg/kg i.v.) of morphine on the inflamed paw. Further, in the L-365,260-pretreated rats, a significant correlation between the antinociceptive effect of the low dose (0.1 mg/kg) of morphine and the intensity of the mechanical hyperalgesia was observed, indicating that the CCK control of the degree of sensitivity to opioids can vary among-the animals. Our data illustrate a differential and limited effect of L-365,260 on opioid antinociception in carrageenin-injected rats, depending on the dose of morphine, the phase of inflammation and the intensity of hyperalgesia.

Animals↗

In mononeuropathic rats, the enhancement of morphine antinociception by L-365,260, a selective CCK(B) receptor antagonist, depends on the dose of systemic morphine and stimulus characteristics.

The ability of the selective cholecystokinin(B) (CCK(B)) receptor antagonist L-365,260 (0.2 mg/kg s.c.) to modulate the antinociceptive action of relatively low doses of systemic morphine (0.1, 0.3 and 1.0 mg/kg i.v.) was evaluated using a well established rat model of peripheral unilateral mononeuropathy. Behavioural tests based on both mechanical (vocalization threshold to paw pressure) and thermal (struggle latency after immersion of the paw into a cold (10 degrees C), warm (44 degrees C) or hot (46 degrees C) water bath) stimuli were used. Experiments were performed 2 weeks after the surgery when the pain-related behaviour has fully developed. We demonstrated a differential effect of L-365,260 depending both on the dose of morphine and the test used. Pretreatment with the CCK(B) receptor antagonist (0.2 mg/kg) inverted the ineffectiveness of the lowest dose (0.1 mg/kg i.v.) of morphine against the noxious (46 degrees C) thermal stimulus, and the effect of the combination was equal to that seen after the dose 0.3 mg/kg of morphine alone. Likewise, in the mechanical test, the already enhanced effect of this dose (0.1 mg/kg) of morphine on the nerve-injured paw was further increased (by 4-fold) after L-365,260 pretreatment. These effects were abolished by naloxone (0.01 mg/kg i.v.). However, the effects of the higher doses (0.3 and 1.0 mg/kg i.v.) of morphine against the mechanical or noxious thermal stimuli were not significantly enhanced by pretreatment with the CCK(B) receptor antagonist. Further, L-365,260 was found to be completely ineffective in modulating the responses to morphine at 10 degrees C and at 44 degrees C.

Analgesics↗

Systemic sclerosis and sarcoidosis, a report of five cases.

We report on five cases of associated systemic sclerosis and sarcoidosis (associated connective tissue diseases). The special peculiarities of this association are emphasized with a review of the literature (14 other cases reported). The clinical aspects, the prognosis, the role of silica, the likelihood of a chance association and the need (in our opinion) to reconsider the name 'sarcoidosis' are discussed.

Adult↗

[Pancytopenia in rheumatoid arthritis treated with methotrexate].

OBJECTIVES: Six cases of pancytopenia were analyzed retrospectively among 350 patients with rheumatoid arthritis treated with methotrexate. Pancytopenia is an uncommon but severe secondary effect of methotrexate. CASE REPORTS: Five patients were hospitalized for infectious complications or hemorrhage with favorable outcome. One patient died due to septic shock. There were risk factors in all 6 patients: 5 were over 65 years of age, creatinine clearance was under 50 ml/min in 4, hypoalbuminemia was found in 4 and methotrexate was combined with an antiinflammatory drug in 4 and with ranitidine in 2. The pharmacological imputability of methotrexate was probable in 4 of the 6 patients. DISCUSSION: Acute pancytopenia in patients treated with methotrexate can be prevented by recognizing risk factors, regular laboratory tests and supplementation of all patients with folic acid according to protocols to be established.

Aged↗

Occurrence of pulmonary complications during methotrexate therapy in rheumatoid arthritis.

Treatment with methotrexate (MTX) in rheumatoid arthritis (RA) can lead to severe side-effects, especially pulmonary and haematological complications. The aim of this retrospective study was to evaluate, during a 6 yr period, the prevalence and severity of bronchopulmonary side-effects in RA patients treated with MTX. A cohort of 130 RA in-patients (106 women, 24 men) treated with MTX was studied for the occurrence of respiratory adverse events. Adverse bronchopulmonary side-effects were observed in 12 patients (two men, 10 women), with a mean disease duration of 15 yr. Only three patients had previously suffered from pulmonary disease. MTX treatment duration was between 1 month and 4.5 yr. The diagnosis was that of hypersensitivity pneumonitis (HSP) in four cases, non-HSP pneumonitis in five patients with one case of Pneumocystis carinii infection, and bronchitis in three cases. The initial respiratory symptoms were not discriminatory between the different conditions. Risk factors were not identified for the occurrence of HSP. HSP always occurred in the first 5 months of treatment. Two patients with HSP died, and another patient with opportunistic infection underwent tracheostomy. HSP represents a potentially lethal side-effect in RA patients treated with MTX. Improved education of patients and physicians should certainly lead to a reduction of both the prevalence and severity of pulmonary side-effects during MTX therapy in RA.

Adult↗