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Biomedical subjects

M Megahed

Publications and source records attributed to M Megahed.

At least 19 recordsLinked to original sources

[Immunology-related chronic progressive cicatricial conjunctival diseases: diagnosis, therapy and prognosis].

PURPOSE: We reviewed the records of patients with chronic cicatricial disease of the conjunctiva for differences in prognosis between clinical and histopathological subgroups of the disease and in therapeutic options. PATIENTS: In 30 patients (58 eyes) with an average age of 69 years (52-86) chronic cicatricial disease of the conjunctiva was diagnosed clinically. Only in 22/30 patients conjunctival biopsies could be performed. The correlation of histopathological and immunohistochemical diagnoses with clinical course under systemic immunosuppression was studied. RESULTS: 15/22 biopsies led to a classification into different subgroups. Under systemic immunosuppression disease ceased to progress for a mean time of 15 months in 13 of 15 patients with positive biopsies and in 9 of 15 without classification. The results after cyclosporine A therapy (4 of 5 patients stabilized after a mean of 27.5 months) and mycophenolate mofetil (8 of 11 patients stabilized at a mean of 7.8 months) were better than those after therapy with dapsone, azathioprine and cyclophosphamide. CONCLUSIONS: Histopathological and immunohistochemical examinations led to a classification in two-thirds of the patients with clinical aspects of chronic cicatricial disease of the conjunctiva. There was no correlation between different histopathological subgroups, success of therapy and prognosis of the disease. There is little hope in using new systemic immunosuppression such as cyclosporine A and mycophenolate mofetil.

Aged↗

RAD, a new immunosuppressive macrolide in murine corneal transplantation.

BACKGROUND: RAD is a novel macrolide immunosuppressant with effects on growth factor signalling. We investigated the potency of RAD in inhibiting allograft rejection in the rat model of orthotopic allogeneic penetrating keratoplasty. METHODS: Fifty-four allogeneic orthotopic penetrating keratoplasties were performed using Fisher rats as donors and Lewis rats as recipients. The animals were divided into five groups: syngeneic control, allogeneic control, RAD 1.5 mg/kg bw per day, RAD 2.5 mg/kg bw per day, cyclosporin A (CSA) 10 mg/kg bw per day. Medication started on the day of operation and continued daily for the duration of 18 days. Each animal was examined by slit-lamp microscopy every 3rd day. For immunohistological evaluation rats were killed on day 14. Immunohistology was performed using monoclonal mouse anti-rat antibodies against CD4, CD8, CD25, CD45 and CD54. RESULTS: The average transplant survival time in the allogeneic combination was 12.3 days (+/- 0.3). Therapy with RAD 1.5 mg/kg and 2.5 mg/kg led to a statistically significant prolongation of transplant survival to 32.3 days (+/- 11.3, P<0.05) and 37.7 days (+/- 12.5), respectively. This efficacy was similar to that of CSA 10 mg/kg (39.7 +/- 12.5 days). There was a statistically significant reduction in the number of CD4+, CD8+ as well as CD45+ cells in both the RAD- and the CSA-treated animals compared with the allogeneic control. CONCLUSIONS: The results show that oral immunosuppression with RAD significantly prolongs corneal allograft survival. Further investigation of RAD in preclinical and clinical high-risk keratoplasty is warranted.

Administration, Oral↗

Phototesting in lupus erythematosus: a 15-year experience.

It has long been observed that sun exposure can induce or exacerbate skin lesions in patients with certain forms of lupus erythematosus. Despite the frequency of photosensitivity in these patients, the mechanism by which ultraviolet radiation alters the pathogenic course of this disease remains poorly understood. After development of standardized test methods, our group demonstrated in 1986 that skin lesions in patients with lupus erythematosus can be experimentally reproduced by UVA and UVB irradiation. In the following years, phototesting has received much attention as a valid model to study photosensitivity of different forms of lupus erythematosus and the pathogenetic mechanism of this disease. Further investigations have also made it possible to find genetic and immunologic factors associated with photosensitivity and have helped to identify the pathophysiologic steps involved in the induction of such skin lesions. We present phototesting results and clinical correlations of more than 400 patients with different forms of lupus erythematosus and discuss the recent advances in provocative phototesting.

Adolescent↗

Treatment of cicatricial pemphigoid with mycophenolate mofetil as a steroid-sparing agent.

BACKGROUND: Cicatricial pemphigoid (CP) is a rare autoimmune bullous disease that affects the skin and mucous membranes. It commonly ends by serious complications such as blindness, stenosis, and stricture formation and is difficult to treat. Mycophenolate mofetil has been reported to be effective in the treatment of pemphigus vulgaris, pemphigus foliaceus, and bullous pemphigoid either as monotherapy or as a steroid-sparing agent. OBJECTIVE: Our purpose was to evaluate the effectiveness of mycophenolate mofetil as a steroid-sparing agent in treating patients with CP. METHODS: Three patients with CP were treated with mycophenolate mofetil and prednisolone. RESULTS: All 3 patients responded very well to the therapy. None of them showed relapse of the disease for a follow-up period of 6 to 14 months after complete cessation of mycophenolate mofetil and prednisolone. No side effects were seen. CONCLUSION: Mycophenolate mofetil appears to be a safe and effective steroid-sparing agent in the treatment of CP.

Anti-Inflammatory Agents, Non-Steroidal↗

Phototesting in lupus erythematosus tumidus--review of 60 patients.

Photosensitivity is an important characteristic feature of several forms of lupus erythematosus (LE), and induction of skin lesions by UV-A and UV-B irradiation has been proved to be an optimal model for evaluating light sensitivity in patients with this disease. Because lupus erythematosus tumidus (LET) has rarely been documented in the literature and is often difficult to differentiate from other photodermatoses such as polymorphous light eruption, we performed photoprovocation tests in 60 patients with LET according to a standardized protocol. Areas of uninvolved skin on the upper back were irradiated with single doses of UV-A (100 J/cm2) and/or UV-B (1.5 minimal erythema dose) daily for three consecutive days. Interestingly, patients with LET are more photosensitive than those with subacute cutaneous lupus erythematosus, and in our study experimental phototesting revealed characteristic skin lesions in 43 patients (72%). Because of the latency period in developing positive phototest reactions, it might be difficult for these patients to link sun exposure with their skin lesions. Furthermore, our data revealed a positive correlation of antinuclear antibodies and positive provocative phototest reactions in these patients as seen for other forms of LE. In conclusion, the high incidence of positive phototest reactions in correlation with the clinical findings, history of photosensitivity and antinuclear antibodies enable the classification of LET as the most photosensitive type of LE.

Diagnosis, Differential↗

Coadministration of the new macrolide immunosuppressant RAD and mycophenolate mofetil in experimental corneal transplantation.

INTRODUCTION: The effect of RAD, a new macrolide immunosuppressant, was examined as mono- and combination therapy with mycophenolate mofetil (MMF) in prevention of acute allograft rejection in murine corneal transplantation. METHODS: Both drugs were administered orally for 18 days beginning at the day of transplantation. The inbred strains Fisher and Lewis were used as donors and recipients, respectively. Five groups were involved: syngeneic control, allogeneic control, 2.5 mg/kg RAD, 40 mg/kg MMF, and double drug therapy with 1.5 mg/kg RAD and 20 mg/kg MMF. RESULTS: The median transplant survival time in the allogeneic combination was 12 (+/-0.3) days. Monotherapy with 2.5 mg/kg RAD and 40 mg/kg MMF led to a statistically significant prolongation of transplant survival to 25.5 (+/-12.5, P=0.0001) days and 19.5 (+/-13.9, P=0.0053) days, respectively. Combination therapy was superior to both monotherapies (100+/-15.8 days, P=0.03). There was a significant reduction in the number of CD4+, CD8+, as well as CD45RA+ cells in the RAD- and double drug-treated animals when compared with the allogeneic control. This significant reduction in graft-infiltrating lymphocytes has not been found in the MMF monotherapy. CONCLUSIONS: The unique finding of this first study on the combination of RAD and MMF in murine corneal transplantation is that double drug therapy produces a highly synergistic effect in prevention of acute allograft rejection without a higher incidence of complications related to drug toxicity or overimmunosuppression.

Animals↗

Lupus erythematosus tumidus--a neglected subset of cutaneous Lupus erythematosus: report of 40 cases.

BACKGROUND: Lupus erythematosus tumidus (LET) is characterized clinically by erythematous, succulent, edematous, nonscarring plaques in sun-exposed areas. Results of histological examination show perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition. The main differential diagnoses are polymorphous light eruption, Jessner's lymphocytic infiltration of the skin, reticular erythematous mucinosis, and pseudolymphoma. Since its first description in 1930, LET has been documented rarely in the literature, and its clinical importance has not been fully appreciated. OBSERVATIONS: We characterized 40 patients with clinical and histological features of LET observed at our department from 1984 through 1998. The onset of the disease clustered in summer because of sun exposure, and 28 (70%) of the patients showed a remarkable photosensitivity confirmed by results of provocative phototesting. A complete resolution of the skin lesions was seen after systemic therapy with antimalarials and, in some cases, with local corticosteroids or spontaneously without any treatment. In 4 (10%) of the patients, antinuclear antibodies were detected; however, there was no evidence of underlying systemic involvement in any of the patients. CONCLUSIONS: Our data constitute the largest number of patients with LET collected until now. The clinical picture, extreme photosensitivity, histological findings, and effective treatment with antimalarials are so characteristic that LET should be considered as a separate entity and differentiated from other variants of cutaneous LE. Arch Dermatol. 2000;136:1033-1041

Adolescent↗

[Presternal verrucous carcinoma].

Verrucous carcinomas represent rare, highly differentiated variants of squamous cell carcinoma. They preferentially develop on the oropharyngeal mucosa (Ackerman tumor), the urogenital mucosa (Buschke-Loewenstein tumors), and the soles of the feet (epitheliomata cuniculata). Various synonyma have been coined for these tumors. We report the uncommon occurrence of a large verrucous carcinoma on apparently uninvolved chest skin of a 79-year old patient. The tumor was excised radically. Complete extirpation was confirmed histologically and there was no sign of recurrence during a 3 month observation period. The clinical appearance, histomorphological features, epidemiological aspects, differential diagnosis, therapy, and nomenclature of verrucous carcinomas are discussed.

Aged↗

[Progressive cicatricial psoriatic alopecia in AIDS].

Scarring alopecia is a rare complication of scalp psoriasis which in most cases occurs in areas of long-standing lesions. A HIV-positive 35 year-old Moroccan patient (CDC C3) developed scalp psoriasis with scarring alopecia within five weeks. Topical antipsoriatic therapy resulted in alleviation of psoriatic lesions and stopped the progression of the alopecia. This case report suggests potential pathogenic links between scalp psoriasis, scarring alopecia, and HIV-infection. In addition, early and efficient antipsoriatic treatment is recommended to prevent the disfiguring complication of scarring alopecia.

Acquired Immunodeficiency Syndrome↗

Allelic losses on chromosome arm 10q and mutation of the PTEN (MMAC1) tumour suppressor gene in primary and metastatic malignant melanomas.

Malignant melanomas frequently show loss of alleles on the long arm of chromosome 10. The PTEN (MMAC1) gene has been identified as a tumour suppressor gene at 10q23.3 that is mutated in various types of advanced human cancers. We have investigated a series of 40 sporadic melanomas from 37 patients (15 primary cutaneous melanomas and 25 melanoma metastases) for allelic losses on chromosome 10, as well as for deletion and mutation of the PTEN gene. Microsatellite analysis revealed loss of heterozygosity at loci located on 10q in tumours from 15 of 34 patients investigated (44%). Somatic PTEN mutations were identified in melanomas from 4 of 37 patients (11%), all of whom had metastatic disease. In two of these patients, the tumours had additionally lost one PTEN allele, indicating complete loss of wild-type PTEN in the tumour cells. Our findings corroborate that loss of heterozygosity on chromosome 10 is a frequent aberration in malignant melanomas and implicate PTEN as a tumour suppressor gene inactivated by somatic mutation in a fraction of these tumours.

Adult↗

Discrete papular mucinosis-a rare subtype of lichen myxoedematosus.

Lichen myxoedematosus is an uncommon and distinct disease entity characterized by cutaneous mucin deposition which, depending on the distribution and overall skin involvement, can be classified into several subtypes. We now describe the case of a discrete papular type of lichen myxoedematosus in a patient without any conspicious laboratory findings including normal thyroid function and the absence of any abnormal immunglobulins.

Diagnosis, Differential↗

Treatment of nonmelanotic hyperpigmentation with the Q-switched ruby laser.

Hyperpigmentation of the skin is often refractory to conventional therapies, but has significant cosmetic implications if located on visible areas. Because laser systems are capable of removing pigment deposits caused by selective photothermolysis, we addressed the issue of whether the Q-switched ruby laser could be a useful alternative in the treatment of nonmelanotic hyperpigmented skin lesions. We report the successful treatment of a patient with hyperpigmentation caused by iatrogenic human herpesvirus 8-associated Kaposi's sarcoma and a patient with hyperpigmentation caused by long-term antimalarial therapy for cutaneous lupus erythematosus. In both patients, clinical lightening of the darkly pigmented lesions was seen after a single treatment, and a significant improvement was observed after 3 laser applications. The patients tolerated the laser therapy well without any short-term side effects and did not experience either scarring or considerable textural skin changes. Histologic examination was performed before and after laser treatment to confirm the reduction of the pigment deposits. Our data indicate that treatment of nonmelanotic skin hyperpigmentation with the Q-switched ruby laser might be a safe and powerful therapeutic method.

Aged↗

[Periorbital edema as the initial symptom of lupus erythematosus profundus. Case report and discussion of the literature].

Periorbital edema may occur initially or in the course of a wide variety of diseases. One of these diseases is lupus panniculitis, a variant of lupus erythematosus, characterized by firm subcutaneous nodules that may ulcerate with subsequent scar formation. We present a case of lupus panniculitis in which the periorbital edema was the initial manifestation. Knowledge about the differential diagnostic possibilities of periorbital edema as well as the different variants of cutaneous lupus erythematosus is important to reach the correct diagnosis.

Diagnosis, Differential↗

Ultraviolet A1 (340-400 nm) phototherapy for cutaneous T-cell lymphoma.

BACKGROUND: The results of a recent study suggested that ultraviolet A1 radiation (UVA1R; 340-400 nm) phototherapy for atopic dermatitis works through induction of apoptosis in skin-infiltrating helper T cells, indicating the possibility that other helper T cell-mediated skin diseases may respond to UVA1R as well. OBJECTIVE: The purpose of this open pilot study was to assess the therapeutic effectiveness of UVA1 phototherapy for cutaneous T-cell lymphoma (CTCL). METHODS: UVA1 phototherapy was used as monotherapy in patients (n = 3) with histologically proven CTCL (stages IA and IB). For daily whole body UVA1 irradiations, either a high-dose (n = 2; 130 J/cm2 UVA1 per exposure) or medium-dose (n = 1; 60 J/cm2 UVA1) regimen was used. Therapeutic effectiveness was assessed clinically and histologically. RESULTS: In each of the 3 patients, skin lesions began to resolve after only a few UVA1 radiation exposures. Complete clearance was observed between 16 and 20 exposures, regardless of whether the high- or medium-dose regimen had been employed. CONCLUSION: These studies suggest that patients with CTCL stages IA and IB can be treated effectively with UVA1 phototherapy.

Aged↗

Multiple basal cell carcinomas associated with hairy cell leukaemia.

We report the case of a caucasian woman who, between the ages of 49 and 51 years, developed multiple (> 20) basal cell carcinomas (BCC). There was no family history of BCC. No abnormalities in the human homologue of the Drosophila segment polarity gene patched (PTCH), glutathione S-transferases T1 and M1, or cytochrome P450 1A1 were detected by polymerase chain reaction (PCR)-based molecular analysis. There was, however, actinic damage of the skin in sun-exposed areas. The patient was diagnosed as having hairy cell leukaemia (HCL) at the age of 51 years, based upon leucocyte morphology as assessed by light and electron microscopy, tartrate-resistant acid leucocyte phosphatase (TRAP) staining, fluorescence activated cell scanning of peripheral blood leucocytes and bone marrow histology. As the leukaemia slowly progressed over a 3-month period, the patient developed four further BCCs. Given that HCL is characterized by a profound defect in T-cell function, it is conceivable that T-cell immune dysregulation can contribute to the pathogenesis of BCC, possibly enhancing the aetiological effect of ultraviolet irradiation.

Basal Cell Carcinoma↗

Polypoid basal cell carcinoma: a new clinicopathological variant.

Basal cell carcinoma (BCC), the most common malignant neoplasm of the skin, has many different clinical and histological appearances. Four patients with a new distinctive form, polypoid BCC, are described. Polypoid BCC is clinically distinguished from other types of BCC by being pedunculated and having a stalk that connects it to the skin surface. Histologically, it is distinctive in that the tumour aggregations are restricted to the exophytic polypoid zone.

Adult↗