Jean Hilaire Saurat

A controlled trial of zidovudine in primary human immunodeficiency virus infection.

BACKGROUND It is possible that antiretroviral treatment given early during primary infection with the human immunodeficiency virus (HIV) may reduce acute symptoms, help preserve immune function, and improve the long-term prognosis. METHODS To assess the effect of early antiviral treatment, we conducted a multicenter, double-blind, placebo-controlled trial in which 77 patients with primary HIV infection were randomly assigned to receive either zidovudine (250 mg twice daily; n = 39) or placebo (n = 38) for six months. RESULTS The mean time from the onset of symptoms until enrollment in the study was 25.1 days. Among the 43 patients who were still symptomatic at the time of enrollment, there was no appreciable difference in the mean (+/- SE) duration of the retroviral syndrome between the zidovudine group (15.0 +/- 4.1 days) and the placebo group (15.8 +/- 3.6 days). During a mean follow-up period of 15 months, minor opportunistic infections developed in eight patients: oral candidiasis in four, herpes zoster in two, and oral hairy leukoplakia in two. Disease progression was significantly less frequent in the zidovudine group (one opportunistic infection) than in the placebo group (seven opportunistic infections; P = 0.009 by the log-rank test). After adjustment for the base-line CD4 cell count, the patients treated with zidovudine had an average gain of 8.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, -1.4 to 19.1) during the first six months of the study, whereas those receiving placebo had an average loss of 12.0 CD4 cells per cubic millimeter per month (95 percent confidence interval, 5.2 to 18.7), for a between-group difference of 20.9 CD4 cells per cubic millimeter per month (95 percent confidence interval, 8.5 to 33.2; P = 0.001). CONCLUSIONS Antiretroviral therapy administered during primary HIV infection may improve the subsequent clinical course and increase the CD4 cell count.

A toxicologic and dermatologic assessment of cyclic and non-cyclic terpene alcohols when used as fragrance ingredients ☆

University of Missouri (Kansas City), c/o American Dermatology Associates, LLC, 6333 Long Avenue, Third Floor, Shawnee, KS 66216, USA Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Avenue, New York, NY 10032, USA Malmo University Hospital, Department of Occupational and Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d Institute for Miliovurdering, Environmental Assessment Institute, Linnesgade 18, 1st Floor, Copenhagen 1361K, Denmark e Technical University of Munich, Institute for Toxicology and Environmental Hygiene, Hohenbachernstrasse 15-17, Freising-Weihenstephan D-85354, Germany Oregon Health Sciences University, Department of Dermatology L468, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA Boston University School of Medicine, Department of Pathology and Laboratory Medicine, 715 Albany Street, L-804, Boston, MA 02118-2526, USA Hospital Cantonal Universitaire, Clinique et Policlinique de Dermatologie, 24, Rue Micheli-du-Crest, Geneve 14 1211, Switzerland Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA 3-27-1 Kaigamori, Aoba-ku, Sendai 981-0942, Japan

A toxicologic and dermatologic assessment of linalool and related esters when used as fragrance ingredients

The RIFM Expert Panel D. Bickers, P. Calow, H. Greim, J.M. Hanifin, A.E. Rogers, J.H. Saurat, I.G. Sipes, R.L. Smith, H. Tagami College of Physicians and Surgeons of Columbia University, Department of Dermatology, 161 Fort Washington Avenue, New York, NY 10032, USA The University of Sheffield, Department of Animal and Plant Sciences, Alfred Denny Building, Western Bank, Sheffield S10 2TN, UK Institute of Toxicology and Environmental Hygiene, Technical University of Munich, Hohenbachernstrasse 15-17, D-85354 Freising, Germany Oregon Health Sciences University, Dept. of Dermatology L468, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201-3098, USA Boston University School of Medicine, Department of Pathology and Laboratory Medicine, 80 E. Concord Street, Boston, MA 02118-2394, USA University Hospital Geneva, Department of Dermatology, CH-1211 Geneva 14, Switzerland University of Arizona, Health Sciences Center, College of Pharmacy, 1703 East Mable Street, Tucson, AZ 85721, USA Imperial College of Science, Technology & Medicine, Division of Biomedical Sciences/Molecular Toxicology Section, Alexander Fleming Building, South Kensington, London SW7 2AZ, UK Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku Sendai 980, Japan

The safety assessment of fragrance materials.

Safety evaluation of the large number of diverse chemicals used as fragrance ingredients follows a systematic prioritization of data generation and analysis, consideration of exposure and critical analysis of the quality of the available information. In prior publications the research priorities used by the Research Institute for Fragrance Materials (RIFM), and the methods of exposure estimation used by industry have been summarized. This paper provides details of the approach used by the RIFM Expert Panel (REXPAN), to examine the dermal effects, systemic toxicity and environmental consequences of the use of and exposure to fragrance materials, which allow a reliable determination of safe use under intended conditions. The key to the usefulness of this analysis is the grouping of more than 2600 discrete ingredients into classes, based on chemical structures. Research sponsored by RIFM, data supplied by member companies, and relevant published reports from many sources are all considered during hazard characterization. A discussion is provided of REXPANs decision tree approach to assessing the dermal, systemic and environmental endpoints and the types and quality of data included. This overall process results in well-documented conclusions which are provided to the International Fragrance Association (IFRA) as the basis for consideration of a new or existing Fragrance Material Standard and to industry for appropriate product risk management actions.

A toxicologic and dermatologic assessment of cyclic acetates when used as fragrance ingredients

An evaluation and review of a structurally related group of fragrance materials.

In Vivo Modulation of Connexins 43 and 26 of Human Epidermis by Topical Retinoic Acid Treatment

After 14 weeks of topical application of 0.1% all-trans-retinoic acid to the napes of volunteers, we observed a 2.5-fold increase in the thickness of epidermis, owing to an increase (p <0.001) in the number and size of keratinocytes and the induction of keratin 6. These changes in the differentiation of epidermal keratinocytes were paralleled by an increase in the amount of Cx43, a connexin that is normally expressed in human epidermis, and by the massive induction of Cx26, which is barely detectable in normal interfollicular epidermis, as judged at both the transcript (Northern blotting) and the protein level (immunolabeling). In contrast, retinoic acid treatment did not alter the morphology and connexin pattern of hair follicles or of sebaceous and sweat glands, and did not induce the expression of other connexins (C32, Cx37, Cx40) in either skin adnexae or epidermis. These observations suggest that the expression of two distinct connexins by interfollicular keratinocytes is related to selective changes in the differentiation program of epidermis that are induced by retinoic acid.

Urticarial pathology in Schnitzler's (hyper-IgM) syndrome

BACKGROUND Schnitzlers syndrome is a rare disorder characterized by chronic urticaria and monoclonal IgM gammopathy. The mechanisms of the urticarial flares remain poorly understood. OBJECTIVE To more accurately define the histopathologic changes in urticarial lesions, we reviewed 25 original biopsies from 15 cases of Schnitzlers syndrome, 11 of which have previously been reported. RESULTS Thirteen specimens from 9 patients showed urticaria with neutrophils (neutrophilic urticaria). Necrotizing leukocytoclastic vasculitis with positive immunofluorescence studies was found only in 2 biopsies from 1 patient who was genetically deficient in C4. Five specimens showed lymphocytic urticaria. Four biopsies demonstrated a spongiotic dermatitis; an eosinophilic spongiosis was seen in 2 biopsies from a patient who later developed pemphigus vulgaris. Epidermal changes were seen in 17 specimens from 10 patients. CONCLUSIONS The histopathologic findings in Schnitzlers syndrome are not uniform although most cases demonstrated neutrophilic urticaria. Neutrophils in Schnitzlers syndrome are not usually related to immune complex vasculitis. Epidermal changes in Schnitzlers syndrome need to be further analyzed.

The incidence of Sweet's syndrome in Geneva : a retrospective study of 29 cases

Over a 12-year period (1979-1991), 29 cases of Sweets syndrome (SS) were detected in the area of Geneva; 24 patients (82%) could be contacted for follow-up. The majority of SS occurred between 1979 and 1986, then from 1991 on. The annual distribution and especially the absence of cases during 4 years suggest an environmental or even infectious factor in SS. Only 4 cases had an underlying disease (ulcerative colitis, polycythemia, lymphoma, sarcoidosis) whereas in the other, a long-term follow-up, including iterative hematological evaluation, did not reveal any underlying condition. Twelve patients were treated by colchicine, 9 by potassium iodide and 5 by prednisone; in 3 patients remission was spontaneous. Nine patients (28%) relapsed; there was no relationship between the type of drugs used and the frequency of relapses.

Bullous pemphigoid and multiple sclerosis: More than a coincidence?

In three patients with long-standing multiple sclerosis, bullous pemphigoid developed. The diagnosis of bullous pemphigoid was based on histologic findings, direct and indirect immunofluorescence, and Western blots showing IgG reacting with the 220 to 240 kD bullous pemphigoid antigen in the serum of three patients. Contrary to previous observations, bullous pemphigoid associated with multiple sclerosis was not different from bullous pemphigoid alone. Three similar cases have been reported previously, so the occurrence of bullous pemphigoid in patients with multiple sclerosis may be more than a coincidence.

Sebum Excretion Rate in Subjects Treated with Oral all-trans-Retinoic Acid

BACKGROUND AND OBJECTIVE It is generally accepted that the inhibition of sebum excretion has a predictive value for anti-acne activity. Whereas oral 13-cisretinoic acid (13-cis-RA) decreases sebum excretion, it has not been shown so far if oral all-trans-retinoic acid (tretinoin, tRA) does so. The aim of this exploratory study was to investigate the effect of oral tRA on the sebum excretion rate (SER) in young male subjects. METHODS 12 healthy volunteers with a baseline SER above 1.0 microgram/cm2/min were treated with 20 mg/day tRA for 4 weeks. The SER was measured at weeks 2 and 4. Adverse reactions were recorded. RESULTS The mean SER varied from 1.56 at baseline to 1.65 at week 2 and to 1.49 micrograms/cm2/min at week 4. Comparison with values obtained in the same subjects previously treated with either 13-cis-RA or 9-cis-retinoic acid indicated that tRA less sebosuppressive. Mucocutaneous reactions and headache were the most frequent side effects of oral tRA. CONCLUSION The lack of effect on the SER suggests that oral tRA would probably be ineffective against acne. The fact that, of the three isomers tested, only 13-cis-RA (which does not bind to nuclear receptors) shows activity may suggest that sebosuppression is not nuclear receptor mediated. We discuss other hypotheses related to pharmacokinetics.