Dominique Parent

Phase II Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Cidofovir Topical Gel for the Treatment of Patients with Human Papillomavirus Infection

Genital condylomata acuminata are nonmalignant human papillomavirus (HPV)-induced tumors in which HPV types 6 and 11 are most commonly found. Usual treatments for condylomata acuminata are nonspecific and are based on the destruction or removal of infected tissue. These procedures are often painful and are characterized by a high relapse rate. We report here what is to our knowledge the first double-blind, placebo-controlled study of the use of cidofovir, a nucleotide analogue, for the treatment of genital papillomavirus infections. Thirty patients were enrolled in the study; 19 received cidofovir, and 11 received placebo. The median number of warts and the median baseline wart area were comparable for both groups. Nine (47%) of 19 patients in the cidofovir group had a complete response (total healing), compared with 0 of the patients in the placebo group (P=.006). None of the patients in the cidofovir group experienced progression of the disease, compared with 5 (45%) of 11 patients in the placebo group. The side effects recorded for both groups were comparable.

Treatment of classical Kaposi's sarcoma with intralesional injections of cidofovir: Report of a case

The effect of intralesional injections of cidofovir, a nucleotide analog with potent in vitro activity against human herpesvirus 8 (HHV‐8), was studied in vivo in an HIV‐negative patient with classical Kaposis sarcoma (KS). After five weekly injections of the drug, no clinical, histological, immunohistological, or virological changes could be detected in comparison with saline‐injected lesions. These findings suggest that, once the KS tumor has developed, active viral replication is no longer involved in the pathogenesis of the disease. Alternative hypotheses are that HHV‐8 replication in blood‐borne cells may foster growth of spindle cells in the skin, or that blocking HHV‐8 may not affect existing lesions but may prevent new lesions from developing. J. Med. Virol. 55:215–218, 1998.

Clinical experience with short schedules of itraconazole in the treatment of tinea corporis and/or tinea cruris

BACKGROUND Superficial fungal infections have usually been considered to be caused only by dermatophytes. In recent years their epidemiology has been changing with other fungi being isolated and, thus, antifungal agents with a broad spectrum of activity, such as itraconazole, may be particularly useful. The risk/benefit ratio for any such treatment is determined by its tolerability profile and the duration of therapy. OBJECTIVE The aim was to compare the efficacy and tolerance of a shorter treatment regimen, using a higher dose of itraconazole, with a standard itraconazole regimen in the treatment of tinea corporis/cruris. METHODS An open study compared oral itraconazole 200 mg daily for 7 days with oral itraconazole 100 mg for 15 days in 153 patients with tinea corporis/cruris. RESULTS At follow-up all patients in both groups were clinically cured or markedly improved. However, mycological cures were greater in the 7-day treatment group (90%), and the onset of clinical and mycological cure was faster in this group. CONCLUSIONS Itraconazole, 200 mg daily for 7 days, offers a short convenient and effective treatment option for tinea corporis and tinea cruris.

Iron induces Bcl-2 expression in human dermal microvascular endothelial cells

Iron is suspected to be involved in the induction and/or progression of various human tumors. The present study was designed to investigate the effects of iron on endothelial cells, keeping in mind that the homeostasis of microvessels plays a critical role in neo-angiogenesis. Applying a model of human dermal microvascular endothelial cell terminal differentiation and death induced by serum deprivation, we found that iron salts (iron chloride and ferric nitrilotriacetate) provided a survival advantage to endothelial cells. Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. Taken together, these observations suggest that iron may give a survival advantage to endothelial cells and represent a novel mechanism through which iron may contribute to tumorigenesis.

The Normal and Pathologic Nail

Clinical diagnosis of nail diseases remains difficult. In effect, a single disease can present widely differing lesions, and, conversely, a given nail malformation can be the expression of a variety of diseases of varying etiology, evolution, and prognosis. It is the area of the nail ihat is affected, rather than the disease itself, that determines the clinical aspect of the nail. It seems, therefore, logical to study ungual pathology, after having examined normal nail structure. Then we will describe diseases of the matrix, diseases of the nail hed and (he hyponychium, and finally, those of the nailplate. This overview does not pretend to be exhaustive. Only those affections most frequently observed by the clinician will be discussed.

Granulomatous vulvitis, granulomatous cheilitis: a single diagnosis?

We report two cases of labial swelling (oral and vulvar) with a granulomatous histology in patients with a history of Crohn’s disease. The differential diagnosis of granulomatous vulvitis and cheilitis, as well as the symptomatology and treatment of vulvar and oral Crohn’s disease are further discussed. To our knowledge, reported cases of vulvar and oral Crohn’s disease are quite scarce in the literature, but the disease might be underdiagnosed. We hope to contribute to an earlier recognition and a better management of the vulvar and oral mucocutaneous lesions of Crohn’s disease.

Renewal and differentiation of keratinocytes cultured on dead de‐epidermalized dermis

Human keratinocytes grown at an air-liquid interface on dead de-epidermalized dermis exhibit a pattern of organization similar to that seen in vivo. Cell renewal is limited to the basal layer. The cell cycle time determined after 7 days of culture, using a percentage labelled mitoses (PLM) technique, was about 15 h. This result is comparable with published data for cultivated keratinocytes but is shorter than the parameter proposed for epidermis in vivo. Appearance of labelled cells in the granular layer was observed 4 days after pulse labelling. Despite this high cell renewal, a normal cell differentiation with expression of various keratinization markers was maintained.

Vulval adenosis associated with toxic epidermal necrolysis

faciale. The role of eosinophilic granulocytes. J Eur Acad Dermatol Venereol 2000; 14:517–18. 6 Smoller BR, Bortz J. Immunophenotypic analysis suggests that granuloma faciale is a gamma-interferon-mediated process. J Cutan Pathol 1993; 20:442–6. 7 Simon HU, Plotz SG, Dummer R, Blaser K. Abnormal clones of T cells producing interleukin-5 in idiopathic eosinophilia. N Engl J Med 1999; 341:1112–20. 8 Lim A, Baron V, Ferradini L et al. Combination of HC-peptide multimer-based T cell sorting with the Immunoscope permits sensitive ex vivo quantitation and follow-up of human CD8+ T cell immune responses. J Immunol Methods 2002; 261:177–94. 9 Casrouge A, Beaudoing E, Dalle S et al. Size estimate of the alpha beta TCR repertoire of naive mouse splenocytes. J Immunol 2000; 164:5782–7. 10 Melamed I, Cohen A, Roifman CM. Expansion of CD3+ CD4– CD8– T cell population expressing high levels of IL-5 in Omenn’s syndrome. Clin Exp Immunol 1994; 95:14–21. 11 Barata LT, Ying S, Meng Q et al. IL-4and IL-5-positive T lymphocytes, eosinophils, and mast cells in allergen-induced late-phase cutaneous reactions in atopic subjects. J Allergy Clin Immunol 1998; 101:222–30. 12 Dummer R, Geertsen R, Ludwig E et al. Sézary syndrome, T-helper 2 cytokines and accessory factor-1 (AF-1). Leuk Lymphoma 1998; 28:515–22. 13 Hautmann C, Gratzl S, Simon D et al. Kutane Zytokin-produzierende T-Lymphomzellen assoziiert mit Atopie und Hypereosinophilie. Hautarzt 1999; 50:743–7. 14 Mempel M, Flageul B, Suarez F et al. Comparison of the T cell patterns in leprous and cutaneous sarcoid granulomas. Presence of Valpha24-invariant natural killer T cells in T-cell-reactive leprosy together with a highly biased T cell receptor Valpha repertoire. Am J Pathol 2000; 157:509–23. 15 Mempel M, Musette P, Flageul B et al. T-cell receptor repertoire and cytokine pattern in granuloma annulare: defining a particular type of cutaneous granulomatous inflammation. J Invest Dermatol 2002; 118:957–66.

In vitro sensitivity of Kaposi's sarcoma cells to various chemotherapeutic agents including acyclic nucleoside phosphonates.

The involvement of a viral agent in the pathogenesis of Kaposis sarcoma (KS) points to antiviral agents as possible therapeutic and/or prophylactic options in the management of the disease. In the present study we investigated the antiproliferative effects of various chemotherapeutic agents, including acyclic nucleoside phosphonates, on the growth of KS-derived cells. Nested PCR amplification demonstrated that these cells do not contain human herpesvirus 8 (HHV-8) DNA sequences. The cytotoxicity of the chemotherapeutic compounds was less pronounced in KS cells than in human dermal microvascular endothelial cells, which are considered to be the normal counterpart of KS cells. Stimulation of KS cells with basic fibroblast growth factor (bFGF) and correction of the IC50 values by the doubling times revealed that the apparent chemotherapeutic resistance of KS cells could mainly be attributed to the long doubling times of these cells. bFGF-stimulated KS cells still exhibited no particular sensitivity to the acyclic nucleoside phosphonates whose activity extends to HHV-8, which is consistent with the absence of linear HHV-8 DNA synthesis in these cells. Our data suggest that neither anti-cancer agents nor antiviral agents such as the acyclic nucleoside phosphonates can discriminate efficiently between KS cells and normal endothelial cells.

Role of viral agents in the pathogenesis of Kaposi's sarcoma

Several viruses have been detected, at various frequencies, in Kaposi’s sarcoma (KS) tissues. The detection of human herpesvirus 8 (HHV-8) in all the epidemiological and histological forms of KS makes it the most attractive candidate causative agent to date. In this report, we discuss the possible explanations for the detection of genomic sequences of various viral agents in KS and the putative role of those viruses in the pathogenesis of the disease.