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Biomedical subjects

P Paquet

Publications and source records attributed to P Paquet.

At least 19 recordsLinked to original sources

Glutathione-S-transferase pi expression in toxic epidermal necrolysis: a marker of putative oxidative stress in keratinocytes.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a dramatic drug-induced emergency related to extensive destruction of the epidermis. There is evidence that its pathomechanism involves impaired detoxication of xenobiotics. Glutathione-S-transferase pi (GST-pi) is a phase II detoxifying enzyme involved in drug metabolization by human keratinocytes. METHOD: Immunohistochemistry was performed in order to assess the expression of GST-pi in keratinocytes of TEN, other cutaneous adverse drug reactions and bullous pemphigoid. RESULTS: GST-pi was disclosed in the involved epidermis of 16/16 TEN patients. It was present in the cytoplasm of suprabasal keratinocytes. GST-pi was also expressed in the clinically uninvolved skin in a majority (8/12) of TEN patients. By contrast, it was rarely and poorly expressed in the other tested dermatoses. CONCLUSION: The pathomechanism of TEN is not related to an impaired quantitative expression of GST-pi. GST-pi expression is an early event in TEN. As oxidative stress is a major inducer of GST-pi, this mechanism might be involved in TEN. Its GST-pi expression mainly restricted to the suprabasal keratinocytes suggests that the pathomechanisms leading to keratinocyte death in TEN are distinct at different levels of the epidermis.

Adult↗

Delayed reepithelialization and scarring deregulation following drug-induced toxic epidermal necrolysis.

A 51-year-old Caucasian woman developed severe drug-induced toxic epidermal necrolysis (TEN) due to allopurinol. The withdrawal of the culprit drug was unfortunately delayed, and dramatic retardation of reepithelialization was observed. At that stage of disease evolution, an inflammatory cell infiltrate was present in the dermis. Coverage of eroded lesions by frozen cultured keratinocyte allografts failed to hasten reepithelialization compared to ungrafted sites. This unusual protracted TEN evolution was followed by the development of extensive hypertrophic and keloid scars. Several biopsies were taken over 6 months. The histologic presentation of the grafted and ungrafted eroded scar tissues looked similar. Both the number and size of the Factor XIIIa-positive dermal dendrocytes, as well as the number of alpha-actin-positive myofibroblasts showed a marked increase between weeks 2 and 12 after grafting. They were reduced after 6 months when the scarring process was stabilized. alpha1 [IV] collagen was never expressed over the eroded scars. Similar to burn patients, delayed reepithelialization might be a risk factor for abnormal scarring in TEN. Cultured keratinocyte allograft apparently offered no improvement in reepithelialization and did not prevent abnormal scarring in this TEN patient.

Allopurinol↗

Absorption, accumulation and biological effects of depleted uranium in Peyer's patches of rats.

The digestive tract is the entry route for radionuclides following the ingestion of contaminated food and/or water wells. It was recently characterized that the small intestine was the main area of uranium absorption throughout the gastrointestinal tract. This study was designed to determine the role played by the Peyer's patches in the intestinal absorption of uranium, as well as the possible accumulation of this radionuclide in lymphoid follicles and the toxicological or pathological consequences on the Peyer's patch function subsequent to the passage and/or accumulation of uranium. Results of experiments performed in Ussing chambers indicate that the apparent permeability to uranium in the intestine was higher (10-fold) in the mucosa than in Peyer's patches ((6.21+/-1.21 to 0.55+/-0.35)x10(-6)cm/s, respectively), demonstrating that the small intestinal epithelium was the preferential pathway for the transmucosal passage of uranium. A quantitative analysis of uranium by ICP-MS following chronic contamination with depleted uranium during 3 or 9 months showed a preferential accumulation of uranium in Peyer's patches (1355% and 1266%, respectively, at 3 and 9 months) as compared with epithelium (890% and 747%, respectively, at 3 and 9 months). Uranium was also detected in the mesenteric lymph nodes ( approximately 5-fold after contamination with DU). The biological effects of this accumulation of depleted uranium after chronic contamination were investigated in Peyer's patches. There was no induction of the apoptosis pathway after chronic DU contamination in Peyer's patches. The results indicate no change in the cytokine expression (Il-10, TGF-beta, IFN-gamma, TNF-alpha, MCP-1) in Peyer's patches and in mesenteric lymph nodes, and no modification in the uptake of yeast cells by Peyer's patches. In conclusion, this study shows that the Peyer's patches were a site of retention for uranium following the chronic ingestion of this radionuclide, without any biological consequences of such accumulation on Peyer's patch functions.

Animals↗

Skin immunoglobulin deposition following intravenous immunoglobulin therapy in toxic epidermal necrolysis.

Human intravenous immunoglobulins (IVIg) which contain anti-CD95 antibodies have been proposed to treat toxic epidermal necrolysis (TEN). Presently, there is no evidence that IVIg reach the keratinocytes in TEN patients. The aim of this study was to assess the Ig distribution in the serum, blister fluid and skin of six consecutive TEN patients treated with IVIg (1 g/kg/day) for 3 days. They were compared with five TEN patients who only received supportive therapy. In all patients, IgA, IgM and IgG concentrations were measured in the serum and blister fluid using an immuno-nephelometric method. Immunohistochemistry was performed on skin biopsies taken from both TEN clinically involved and uninvolved skin to search for IgG deposits. On admission, the IgG concentrations were significantly higher in both TEN serum and TEN blister fluid compared with their respective IgA and IgM contents. The IgG, IgA and IgM concentrations in blister fluid were significantly lower than their respective serum concentrations. The serum and blister fluid IgG concentrations, but not that of IgA and IgM, were markedly increased at the completion of the IVIg treatment. By contrast, they remained unchanged in the TEN patients that were untreated with IVIg. In the IVIg-treated patients, the IgG intraepidermal deposits raised markedly in both TEN-involved and uninvolved skin. This was not the case in patients who did not receive IVIg. These results suggest that IVIg perfusions brought a prominent increase in IgG concentration in the serum, blister fluid and epidermis of both TEN-involved and clinically uninvolved skin. The presence of potentially protective IgG in TEN epidermis following IVIg treatment could help limiting the disease progression.

Adolescent↗

Healing effect of ketanserin on chronic leg ulcers in patients with diabetes.

BACKGROUND: The treatment of chronic leg ulcers remains a stubborn problem in many patients. Topical 2% ketanserin ointment, a 5HT2-serotoninergic blocking agent, has been reported to improve healing of decubitus, venous, diabetic and ischaemic ulcers. METHOD: The present double-blind intra-individual comparative study was performed in 12 women with diabetes presenting with at least two similar leg ulcers. In each subject, the two lesions were randomly assigned to be treated for 8 weeks by 2% ketanserin ointment or its unmedicated vehicle. OBJECTIVE: assessments of the dynamics of wound healing were performed using computerized morphometry. Evaluations were performed at 2-week intervals for 8 weeks. RESULTS: A significant decrease in relative wound area was observed on the ketanserin-treated ulcers compared with the placebo group. CONCLUSION: Topical ketanserin is a valuable therapy for difficult-to-treat leg ulcers.

Administration, Cutaneous↗

[DRESS syndrome to sulfasalzine].

We report a case of drug hypersensibility syndrome (DRESS syndrome) developed one month after initiation of a treatment by sulfasalazine. Due to the severity of the cytolytic hepatic damages as observed in this case, we emphasize the importance of suggesting this diagnosis in any patient developing a cutaneous rash and an alteration of the general health status after initiation of a new treatment. The hematologic alterations which represent a key feature for the diagnosis may rash. develop only a few days after the cutaneous rash.

Adult↗

Cystic lesion of the parotid following drug-induced toxic epidermal necrolysis (Lyell's syndrome).

A 32-year-old woman developed a unilateral cyst of the duct of parotid gland 4 months after severe oral involvement of drug-induced toxic epidermal necrolysis (TEN). The pathomechanism leading to the TEN epidermal destruction had presumably involved the salivary epithelium as well, leading to the development of the cystic lesion. The patient had low serum lipase levels, but high serum amylase levels at the time of TEN. These serological markers could represent a clue for the risk of developing cystic lesions of the large salivary glands following TEN.

Adult↗

[Artificial sources of light].

The artificial light sources are numerous. They emit a more or less delimited spectrum of wavelengths. Ultraviolet light dosimetry allows to control the amount of delivered energy.

Dose-Response Relationship, Radiation↗

[Laser and pulsed light treatments].

Numerous types of lasers can exert different and specific effects in the skin. Devices delivering high intensity of pulsed light can exert similar effect.

Humans↗

[How I treat ... basal cell carcinoma by imiquimod].

Basal cell carcinoma is the most frequent cancer in humans. Several clinical types are distinguished. They are bound to distinct evolutive prognosis. The surgical excision is the treatment of choice which is rarely followed by recurrence. However, when the lesion is superficial and non aggressive and when the body site is adequate, topical applications of imiquimod can provoke the neoplastic regression. This type of immunotherapy brings 70 to 90% complete remission. A medical follow-up of the treated site is mandatory for a couple of years.

Adjuvants, Immunologic↗

[How I treat ... lentigo maligna by topical imiquimod].

Lentigo maligna is a special form of in situ cutaneous melanoma that develops on the face of sun worshipers. The topic immunostimulator imiquimod can destroy the neoplasm before it expresses its invasive potential. A strict clinical follow-up of the treated zone must be observed at least 5 years to detect any early sign of recurrence.

Administration, Topical↗

[Cutaneous adverse effects of lithium].

Oral administration of lithium is used as treatment in psychiatry. The drug frequently induces cutaneous side effects corresponding to acneiform or maculo-papular eruptions, psoriasis and folliculitis. Men are more frequently affected than women. These manifestations are characterized by the accumulation of neutrophils in the skin. Alopecia and classical drug reactions are also possible. Topical applications of lithium used to treat some dermatoses do not induce similar side effects, probably because dosages are much lower.

Administration, Oral↗

[Dapsone treatment of folliculitis decalvans].

BACKGROUND: Folliculitis decalvans consists of recurrent patchy painful folliculitis of the scalp causing scarring alopecia. The physiopathology of this condition is still unclear, but is likely a manifestation of chronic neutrophilic bacterial folliculitis. Numerous topical and systemic treatments (corticosteroids, antistaphylococcal antibiotics) have been used with variable results. Based on the dapsone antimicrobial activity and its anti-inflammatory action especially directed to the neutrophil metabolism, we treated two patients with severe folliculitis decalvans with this drug. CASE REPORTS: The patients were treated with dapsone at a daily dose of 75 and 100 mg, respectively for 4 to 6 months. After 1 and 2 months, pustular folliculitis progressively cleared, leaving a residual non inflammatory cicatricial alopecia. When maintaining a dapsone dosage at 25 mg/day no relapse occurred during 3 years and 1 year, respectively. No important adverse effect to dapsone was evidenced. After dapsone withdrawal, a moderate relapse of the disease with pruritus and folliculitis occurred after a few weeks in both cases. The disease relapse rapidly cleared after dapsone reintroduction at a daily dose of 25 mg. COMMENTS: Dapsone at moderate dosage was well tolerated and rapidly effective in treating the two cases of folliculitis decalvans. A long term and low dose (25 mg daily) maintenance treatment avoided disease relapses.

Adult↗

[Severe paroxysmal drug eruptions].

Some drug reactions showing cutaneous expression exhibit a paroxysmal course. These diseases encompass the toxic epidermal necrolysis, the drug hypersensitivity syndrome, and the acute generalized exanthematic pustulosis. These syndromes are associated with dismal outcome. They represent medical emergencies needing hospitalization in specialized care units.

Acute Disease↗

[How I treat... the critical bacterial colonization of a leg ulcer. The Yin and the Yang features of silver-based dressings].

The critical bacterial colonizaion of leg ulcers can impair their healing rate, aggravate the patient discomfort and increase the medical and nursing costs. In recent times, the dressings designed for leg ulcers have followed a pace of conceptual revolution. Some of them are now offered containing an antiseptic of the silver salt family. The silver concentraton delivered into the wound bed is important to consider when assessing treatment efficacy. The diversity of the silver-based dressings currently on the European market is as large as their differences in activity. Only a minority of these dressings adequately control the wound biocenosis. Their cost which is high for the patient, must be compared to that of nursing care that may become less important. The expected beneficit is a reduction in healing time.

Anti-Infective Agents, Local↗

[Adverse cutaneous reactions to antidepressants].

Due to the widespread usage of antidepressants by the population, they represent a class of drugs which is at high risk for cutaneous side effects. The diversity in the clinical presentations is large. The variability in their severity is large as well. Morbidity may be quite severe, but the vital prognosis is rarely affected.

Alopecia↗

[Leg heaviness and stasis microangiopathy. Preventive and therapeutic approaches].

Venous insufficiency of the legs is a frequent and insidious disorder which, through its consequences' cascade, lead to some cutaneous microangiopathy with relative ischemia. Chronic leg ulcer is the late issue of the process accompanied by varied medical and socio-economic aspects. The pathogeny of the cutaneous lesions is directly related to alterations in hemorrheology and leukocyte adhesion inside capillaries. Elastic contention and some venotropic drugs exert preventive effects on the development of leg ulcers. They also bring some therapeutic improvement of the symptoms of leg heaviness.

Diabetic Angiopathies↗

[How I treat ... hypertrichosis].

Hypertrichosis can result from various origins and exhibit diverse clinical presentations. Any etiological treatment, when available, does not always lead to regression of the excess in pilosity. Most often, hypertrichosis represents a real esthetic burden and affects the patient's self-esteem. Currently the laser epilation technique offers new and promising therapeutic possibilities.

Humans↗