Search PubMed⌕ Search

Biomedical subjects

C L Leonardi

Publications and source records attributed to C L Leonardi.

At least 19 recordsLinked to original sources
PubMed2005

The tumour necrosis factor-alpha inhibitor adalimumab rapidly reverses the decrease in epidermal Langerhans cell density in psoriatic plaques.

BACKGROUND: The pathophysiology of psoriasis is poorly understood, and the mechanism of action of biological agents interfering with tumour necrosis factor (TNF)-alpha that improve psoriatic plaques is completely unknown. OBJECTIVES: To begin to unravel the mechanism of action, cellular changes occurring in plaques following administration of adalimumab, a humanized monoclonal antibody against TNF-alpha, were investigated. METHODS: Thirteen different patients underwent sequential biopsies as part of a clinical trial. Each biopsy was immunostained and evaluated to calculate the relative density of epidermal Langerhans cells (LCs) before and after treatment (days 2, 7, 28, 84). To explore the basis for reduced epidermal LC densities in plaques, a SCID-Hu animal model was utilized. Acute psoriatic lesions were created within 2 weeks by injection of superantigen-activated CD4+ T cells into engrafted symptomless skin. RESULTS: Compared with symptomless skin, untreated plaques had a significantly reduced density of epidermal LCs. There was a rapid increase in density of epidermal LCs in plaques following treatment with adalimumab beginning as early as day 7. The paucity of epidermal LCs in plaques was contrasted to the prominent density of LCs in other skin disorders with chronic inflammation and alterations in keratinization, including lichen planus and inflamed seborrhoeic keratosis. Rapid creation of plaques using the SCID-Hu model was accompanied by loss of epidermal LCs, indicating that diminished LC density occurs at an early stage of lesion formation. CONCLUSIONS: These data shed light on a new immunopathological perspective highlighting a rapid loss of epidermal LCs in acute psoriatic lesions, with sustained decreased density of LCs in chronic plaques. Furthermore, an unexpected insight into the mechanism of action was uncovered for adalimumab, in which rapid restoration of epidermal LC density was observed.

Adalimumab↗
PubMed1998

Role of Mycobacterium paratuberculosis in Crohn's disease: a prospective, controlled study using polymerase chain reaction.

PURPOSE: Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohn's disease. The purpose of this study was to determine whether M. paratuberculosis was present in tissue from patients with Crohn's disease in a defined geographic area. METHODS: We prospectively evaluated, using polymerase chain reaction and culture, whether M. paratuberculosis was present in 44 specimens (37 from intestinal mucosal biopsies and 7 from surgical resections) from patients with Crohn's disease, ulcerative colitis, or normal colonic mucosa. RESULTS: Of the 25 specimens tested from the 21 Crohn's patients, only 1 positive specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction. Cultures of all specimens revealed no growth of M. paratuberculosis. CONCLUSION: M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohn's disease. These results do not support a common causative role of M. paratuberculosis in Crohn's disease.

Adolescent↗
PubMed1996

Dermatomal lichenoid chronic graft-vs-host disease following varicella-zoster infection despite absence of viral genome.

Localized cutaneous graft-versus-host disease (GVHD) following a dermatomal distribution or in a pattern of Blaschko's lines. Some authors have postulated that dermatomal GVHD is triggered by a varicella-zoster virus infection, although in reported cases, there was no history of a preceding herpes zoster. We describe a case of GVHD localized to the exact dermatome of a culture-proven varicella-zoster virus infection. PCR analysis failed to detect persistence of viral genome in the affected skin.

Adolescent↗
PubMed1996

Cutaneous reactions following herpes zoster infections: report of three cases and a review of the literature.

Three patients, one healthy and two immunocompromised, developed cutaneous reactions that histologically mimicked granuloma annulare at sites of resolved varicella-zoster virus (VZV) reactivation infections. Variable latency periods between the infection and the granulomatous reaction were noted. As in other case reports, the presence of VZV DNA in these lesions was inconsistently demonstrated by the polymerase chain reaction (PCR) and appears more common in early, as opposed to late, post-zoster granulomas. In addition to various granulomatous reactions, vasculitic and neoplastic eruptions following resolved VZV infections have been described and are reviewed here. Therapeutically, topical, intralesional and systemic corticosteroids, as well as acyclovir, have been tried with inconsistent results. Although the pathogenesis remains unclear, the presence of VZV DNA in early lesions that histologically do not display viral cytopathic changes, suggests the virus induces an atypical delayed hypersensitivity reaction not affected by antiviral therapy.

Adult↗
PubMed1995

Detection of herpes simplex and varicella-zoster infection from cutaneous lesions in different clinical stages with the polymerase chain reaction.

BACKGROUND: The polymerase chain reaction (PCR) can be used to diagnose a variety of infectious processes. OBJECTIVE: We sought to determine whether Tzanck smear debris, vesicle fluid swabs, crusts, or fixed tissue specimens are the best source for template herpes simplex virus (HSV) or varicella-zoster virus (VZV) DNA for the PCR. METHODS: Patients with both clinical and histologic evidence of HSV (n = 6) or VZV (n = 16) infection were examined. Stained Tzanck smears, vesicle fluid swabs, dried crusts, and skin biopsy specimens were obtained at the same time from each patient. DNA was extracted from the different clinical specimens and then examined for HSV or VZV DNA with PCR. Fifteen control subjects did not have clinical or histologic evidence of herpesvirus infection. RESULTS: In cases of suspected VZV infection, PCR detected VZV DNA sequences from all 15 Tzanck smears, all 15 vesicle swabs, one of one crust, and 14 of 16 fixed tissue specimens. HSV DNA sequences were detected from all six Tzanck smears, all four vesicle fluid swabs, two of two crusts, and five of six fixed tissue specimens. CONCLUSION: PCR can detect VZV and HSV DNA sequences from a variety of sources including formalin-fixed tissue specimens. Although viral DNA was detected slightly more frequently from Tzanck smear debris, crusts, and vesicle fluid swabs compared with fixed tissue specimens, each was an excellent source of target DNA for the PCR to confirm the diagnosis of herpesvirus infection.

Chickenpox↗
PubMed1995

Analysis of the polymerase chain reaction in the detection of herpesvirus DNA from fixed and stained tissue sections.

BACKGROUND AND DESIGN: The polymerase chain reaction (PCR) is a molecular diagnostic technique that has been applied to many infectious processes. Stained and unstained Tzanck smears, vesicle fluid swabs, and crusts have all been used as the source for template DNA for the PCR to document evidence of herpes simplex virus and varicella-zoster virus infection. Thirty-five cases with histologic evidence of acute herpesvirus infection were retrieved from archival tissue blocks that were up to 5 years old. Paraffin and hematoxylin-eosin-stained tissue sections obtained from routinely prepared glass slides from these cases were then examined for herpesvirus DNA using the PCR. RESULTS: The PCR-detected herpesvirus DNA from 34 (97.1%) of 35 paraffin tissue samples. Herpes simplex virus and varicella-zoster virus DNA were detected in eight and 26 of these cases, respectively. For hematoxylin-eosin-stained tissue samples, PCR detected herpesvirus DNA sequences in 16 (45.7%) of 35 cases. Herpesvirus DNA was isolated from paraffin tissue sections and recently prepared hematoxylin-eosin-stained tissue samples obtained from archival tissue blocks that were up to 5 and 2 years old, respectively. CONCLUSIONS: The PCR can detect herpesvirus DNA in extremely high yield from unstained paraffin-embedded tissue samples with histologic evidence of acute herpesvirus infection that are up to 5 years old. Herpesvirus DNA can also be identified in approximately 50% of these cases from hematoxylin-eosin-stained tissue sections obtained from routinely prepared glass slides.

DNA, Viral↗
PubMed1993

Disseminated infection with Trichosporon beigelii. Report of a case and review of the cutaneous and histologic manifestations.

BACKGROUND: Trichosporonosis is a potentially life-threatening disseminated infection with Trichosporon beigelii, the causative agent of the white piedra. Systemic infection by this fungus has been most frequently described in immunocompromised hosts with neutropenia, but one case has been reported in the acquired immunodeficiency syndrome setting. We report a second case of trichosporonosis in a patient with acquired immunodeficiency syndrome and review the clinical and histologic characteristics of cutaneous involvement with this opportunistic fungal pathogen. OBSERVATIONS: Trichosporonosis occurs most commonly in neutropenic patients receiving chemotherapy. We describe the second case developing in the acquired immunodeficiency syndrome setting. Cutaneous involvement occurred in approximately 30% of patients and most frequently presented as purpuric papules and nodules with central necrosis or ulceration. Biopsy specimens of these lesions revealed dermal invasion by fungal elements, and culture was positive in greater than 90% of the cases. CONCLUSIONS: Disseminated infection with T beigelii can occur in immunosuppressed patients, including those with acquired immunodeficiency syndrome particularly if associated with neutropenia. Cutaneous involvement is common, presenting as purpuric papules and nodules. Biopsy and culture of cutaneous findings can help establish an accurate diagnosis resulting in rapid and appropriate treatment.

AIDS-Related Opportunistic Infections↗
PubMed1993

Identification of Mycobacterium tuberculosis DNA in a case of lupus vulgaris.

A variety of cutaneous lesions are believed to result from the presence of Mycobacterium tuberculosis. Demonstration of M. tuberculosis directly or in culture in some of these eruptions can be difficult. We studied a typical case of lupus vulgaris that had been followed for several years with frequent unrewarding biopsies and cultures to see if M. tuberculosis DNA could be demonstrated in skin biopsy specimens. We used the polymerase chain reaction and a primer/probe set specific for a region in the gene for the 65 kd antigen of M. tuberculosis to search for M. tuberculosis complex DNA. M. tuberculosis complex DNA was demonstrated in archival skin biopsy specimens from the lesion of lupus vulgaris. The polymerase chain reaction and specific primer/probe sequences can be used to demonstrate M. tuberculosis complex DNA in skin lesions. A variety of skin lesions believed to be related to tuberculosis (tuberculids) can be revisited with these techniques and studied for the presence of an infectious agent.

Base Sequence↗
PubMed1993

An evaluation of oral ulcers in patients with AIDS and AIDS-related complex.

BACKGROUND: Patients with HIV infection can have recurrent and persistent oral ulcers, not attributable to known infectious agents. OBJECTIVE: Our aim was to evaluate prospectively oral ulcers in patients with HIV infection to determine whether an etiologic agent could be identified. METHODS: Sixteen patients with HIV infection who had oral ulcers not attributable to known causes had culture of the base and a biopsy specimen taken from the ulcer. Cultures were obtained for herpes simplex and varicella-zoster viruses, mycobacteria, and fungi. By polymerase chain reaction (PCR) analysis with primer/probe sets for herpes simplex viruses 1 and 2, varicella-zoster virus, cytomegalovirus, human papillomavirus, and Mycobacterium tuberculosis, each biopsy specimen was analyzed for the presence of DNA from these organisms. Specimens were also evaluated histologically. RESULTS: Histoplasmosis was detected histologically in one biopsy specimen, candidiasis in a second, and herpetic changes in a third. Viral cultures were positive for herpes simplex virus 1 in four cases and herpes simplex virus 2 in one case. PCR analysis detected DNA for herpes simplex virus 1 in one case and herpes simplex virus 2 in another; DNA from other pathogens was not identified. In the remaining eight patients, hematoxylin-and-eosin staining revealed eosinophilic ulcers in five cases and nonspecific changes in three cases. CONCLUSION: The etiologic agent of recurrent or persistent oral ulcers in patients with AIDS and AIDS-related complex was not identified in 50% of patients. PCR analysis was not useful. Herpes simplex virus or other pathogens were not detected in ulcers containing numerous eosinophils.

AIDS-Related Complex↗
PubMed1993

Identification of Mycobacterium tuberculosis DNA in five different types of cutaneous lesions by the polymerase chain reaction.

BACKGROUND AND DESIGN: A spectrum of skin lesions are believed to be secondary to the presence of Mycobacterium tuberculosis. Demonstration of M tuberculosis directly or in culture in some of these eruptions can be difficult. We used the polymerase chain reaction and a primer/probe set specifically for M tuberculosis complex DNA to evaluate five types of skin lesions clinically considered to represent infection by, or reaction to, M tuberculosis. OBSERVATIONS: Mycobacterium tuberculosis DNA was demonstrated in paraffin-embedded sections of these five cases, representing a variety of clinical and histologic patterns. In two cases, M tuberculosis could not be demonstrated by routine cultural methods. CONCLUSION: DNA diagnostic methods such as the polymerase chain reaction can be used to rapidly identify cutaneous lesions produced by M tuberculosis.

Adult↗
PubMed1992

Comparison of Tzanck smear, viral culture, and DNA diagnostic methods in detection of herpes simplex and varicella-zoster infection.

OBJECTIVE: To compare Tzanck smears, viral cultures, and DNA diagnostic methods using the polymerase chain reaction (PCR) in detection of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection in clinically suspected cases. DESIGN: A 12-month trial comparing PCR with viral cultures and Tzanck smears in patients with clinically suspected HSV or VZV infection. SETTING: Both ambulatory and hospitalized patients were recruited from a tertiary referral center and the Miami (Fla) Veterans Affairs Medical Center. PATIENTS: Convenience samples of patients clinically suspected to have HSV (n = 48) or VZV (n = 35). To be included in the final analysis patients needed to have a positive Tzanck smear, viral culture, or PCR result. Patients who were clinically suspected to have HSV but had VZV by viral culture or PCR were analyzed in the VZV group. Similarly, patients who were clinically suspected to have VZV, but had HSV by viral culture or PCR were analyzed in the HSV group. Seventy-seven patients were available for final analysis: HSV (n = 30), VZV (n = 32), and 15 control cases who did not have evidence of viral infection. RESULTS: For HSV, PCR detected HSV DNA sequences in 73% of stained smears and 83% of unstained smears. For VZV infection, VZV DNA sequences were detected in 88% of stained smears and 97% of unstained smears. Viral DNA sequences were not detected in the 15 control cases. Viral cultures were positive in 83% and 44% of HSV and VZV cases, respectively. The Tzanck smear was positive in 60% and 75% of HSV and VZV cases, respectively. CONCLUSIONS: PCR is a reliable method for detecting HSV and VZV DNA sequences from single stained and unstained Tzanck smears. It is clearly superior to viral culture in identifying VZV infection and is equivalent to conventional culture techniques in identifying cases of HSV.

Chickenpox↗