Bernard Leroy

Cerium(IV)-Catalyzed Deprotection of Acetals and Ketals under Mildly Basic Conditions.

Smooth and quantitative deprotection of a wide range of acetals and ketals [Eq. (a); R, R(1)=alkyl, aryl, H] under neutral to mildly basic conditions was achieved with catalytic quantities of cerium ammonium nitrate (CAN). The reaction conditions are compatible with a variety of sensitive functional groups, and aldehydes can be liberated from acetals without being oxidized to the corresponding carboxylic acids.

A novel therapy for atopic dermatitis with allergen-antibody complexes : a double-blind, placebo-controlled study

BACKGROUND Exposure to airborne allergens exacerbates symptoms of atopic dermatitis (AD) in hypersensitive patients. OBJECTIVE Our purpose was to determine whether the administration of allergen-antibody complexes would improve the symptoms of AD. METHODS Twenty-four adults with AD and hypersensitivity to Dermatophagoides pteronyssinus (Dpt) were treated in a double-blind, placebo-controlled trial by intradermal injections of complexes containing autologous specific antibodies and Dpt allergens. After 4 months, placebo-treated patients started receiving active treatment. All patients were treated for a full year. Clinical status and Dpt-specific IgG and IgE antibody levels were monitored. RESULTS Symptoms of AD subsided within a few weeks after starting therapy, with significant reduction after 4 months in treated patients only. After 1 year, 82% of the patients exhibited a mean improvement of 83%, associated with reduction of Dpt-specific IgG antibodies. CONCLUSION The treatment of Dpt-sensitive patients with AD by injections of allergen-antibody complexes is safe and effective in a majority of patients.

REMARKABLY EFFICIENT DEPROTECTION OF CYCLIC ACETALS AND KETALS

A simple and mild procedure for the efficient deprotection of cyclic acetals and ketals, using cerium ammonium nitrate (CAN) is reported. The method tolerates a range of functional and protecting groups and is suitable for acid-labile substrates

Efficient and stereocontrolled synthesis of polysubstituted tetrahydropyrans by an allylstannylation/Bi(III)-promoted cyclisation strategy

A novel sequence, involving the condensation between a highly functionalised allylstannane and various aldehydes, followed by a bismuth triflate-promoted intramolecular Sakurai cyclisation (IMSC) of the resulting homoallylic alcohols, allows a rapid and stereocontrolled access to a range of polysubstituted tetrahydropyrans

Real-life practice study of the clinical outcome and cost-effectiveness of photodynamic therapy using methyl aminolevulinate (MAL-PDT) in the management of actinic keratosis and basal cell carcinoma

Clinical trials have shown that photodynamic therapy using methyl aminolevulinate (MAL-PDT) is an effective treatment for actinic keratosis (AK), and nodular and superficial basal cell carcinoma (nBCC and sBCC) unsuitable for other available therapies. Economic evaluation models have shown that it is a cost effective intervention as well. The objectives of this prospective, observational, one arm study were (i) to verify in a real-life practice study the results obtained in previous clinical trials with MAL-PDT in the treatment of AK, nBCC and sBCC; (ii) to calculate the real-life cost of treatment and validate predictions from an economic evaluation model. Patients with AK and/or BCC were selected according to Belgian reimbursement criteria for treatment with MAL-PDT. Clinical response, cosmetic outcome and tolerability were assessed. MAL-PDT cost was calculated and compared to published model cost data. Data were collected from 247 patients (117 AK, 130 BCC). A complete clinical response was obtained for 83% of AK (85/102) and BCC (97/116) patients. A good or excellent cosmetic outcome was obtained for 95% of AK patients and 93% of BCC patients. Tolerability was good: only 2 patients withdrew for adverse events. Clinical results were similar to previous studies. Total cost of care per patient was euro 381 for AK, euro 318 for nBCC, and euro 298 for sBCC. Total cost per lesion was euro 58 for AK (identical to model prediction), euro 316 for nBCC and euro 178 for sBCC (both within 20% of model prediction). The clinical results of MAL-PDT in this real-life practice study confirm those demonstrated in previous clinical trials. Costs calculated from this study confirm predicted cost-effectiveness in the original model for MAL-PDT in the management of AK and BCC.

Injection of allergen-antibody complexes is an effective treatment of atopic dermatitis.

Atopic dermatitis (AD) can be exacerbated by contact with airborne allergens, amongst which Dermatophagoides pteronyssinus (Dpt) appears to be potentially important. Specific IgE antibodies towards Dpt are often found in AD, and it can therefore be speculated that suppression of the production of anti-Dpt IgE might result in a significant clinical improvement. Complexes of antigen and specific antibodies have been shown to suppress the production of antibody in other systems; we report here the evaluation in an open trial of the capacity of such complexes to improve symptoms of AD. Ten adult patients were enrolled in this study. In addition to satisfying the criteria of AD, they all suffered from a severe disease (more than 20% of the body surface involved) that had been stable for at least the last 2 years. The patients had high titers of total IgE antibodies and specific anti-Dpt antibodies. Allergen-antibody complexes were prepared from Dpt allergens and an excess of autologous specific anti-Dpt antibodies obtained by immunoadsorption. The patients received regular injections of these complexes throughout 1 year, during which clinical parameters of disease intensity, percentage of body surface affected and intensity of pruritus were regularly monitored. A significant clinical improvement was obtained after 3-4 months of therapy and was maintained through the 9th month. After 1 year of treatment, 2 patients were completely free of disease, 4 had residual lesions which continued to improve and 4 patients had a partial recurrence of dermatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunotherapy of Atopic Dermatitis by Injections of Antigen-Antibody Complexes

The effectiveness and safety of injections of complexes made of specific anti-allergen antibodies and allergen was confirmed in a double-blind placebo-controlled trial with adult patients suffering from atopic dermatitis.

Efficient and connective synthesis of substituted butyrolactones and exo-methylene butyrolactones

A variety of alpha-(trimethylsilylmethyl)- substituted butyrolactones are readily accessed by a novel tandem ene-reaction/oxidative desilylation of a range of aldehydes, Subsequent functionalisation led to an efficient methodology for the preparation of exo-methylene butyrolactones

Remarkable effect of basic ligands in the lanthanide-catalysed enantioselective cycloadditions of 3-carbomethoxy-2-pyrone (3-CMP)

The key-role of basic ligands in attaining high enantiomeric excess in the lanthanide catalysed asymmetric cycloadditions of 3-CMP is reported, A model, rationalising all our previous observations is discussed

Allergen-sensitive atopic dermatitis is improved by injections of allergen combined with F(ab')2 fragments of specific antibodies.

Summary Symptoms of atopic dermatitis (AD) can be provoked by exposure to airborne allergens. We have previously shown that patients hypersensitive to D. pteronyssinus (Dpt) allergens were improved by administration of complexes composed of specific antibodies and allergen, which reduce the allergen‐specific immune response. We now report that similar results can be achieved by using F(ab′)2 fragments of specific antibodies instead of whole antibody molecules. Eight adult patients with severe AD were included in a single‐blind study. During the first 11 months patients were maintained on injections of carrier buffer alone, in an effort to evaluate the extent of spontaneous improvement. They were then treated with intradermal injections of allergen‐F(ab′)2 complexes made from autologous specific antibodies and Dpt allergens. The majority of the patients improved spontaneously during the summer months, with an average 30% reduction of symptoms. However, a much more pronounced improvement was observed after 3 months on active therapy, corresponding to a cumulative amount of 60 μg F(ab′)2 and 15 μg allergens. The patients continued to improve over the next 5 months, showing an average 83% reduction of severity scores. The use of F(ab′)2 antibody fragments reduces the risk of inducing an anti‐allotypic immune response, and raises the possibility of adding adjuvants to allergen‐antibody complexes and/or using specific antibodies isolated from pooled gammaglobulins.