Biomedical subjects

Francisco Max Damico

Publications and source records attributed to Francisco Max Damico.

6 recordsLinked to original sources

PubMed2005

T-cell recognition and cytokine profile induced by melanocyte epitopes in patients with HLA-DRB1*0405-positive and -negative Vogt-Koyanagi-Harada uveitis.

PURPOSE: Vogt-Koyanagi-Harada disease (VKH), an autoimmune disease targeted against melanocytes, is associated with HLA-DRB1*0405. This study was undertaken to analyze T-cell recognition and the cytokine expression profile induced by melanocyte epitopes in HLA-DRB1*0405-positive and -negative patients with VKH uveitis. METHODS: Peripheral blood mononuclear cells (PBMC) proliferation and Th1 (IFN-gamma) and Th2 (IL-4 and IL-5) cytokine production were analyzed in HLA-DRB1*0405-positive (n = 12) and -negative (n = 22) patients with VKH and HLA-DRB1*0405-positive (n = 9) and -negative (n = 8) control subjects in response to human melanoma cell line lysate (HMCLL) and 28 synthetic peptides derived from the human melanocyte differentiation proteins TYR, TRP1, TRP2, and Pmel17. The peptides were selected using the TEPITOPE algorithm, based on their predicted binding to HLA-DRB1*0405 and to the non-disease-related HLA-DRB1*15. RESULTS: HMCLL was recognized exclusively by the patients' PBMC (44%) but not by those of the control subjects (P < 0.01). PBMC from patients with VKH recognized an increased breadth of melanocyte-derived peptides at lower peptide concentrations than in the control subjects (68% vs. 25%; P < 0.01, at 1 microM) and did not produce the Th2 cytokine IL-4 in response to disease-specific peptides (0% vs. 50%, P < 0.001). Five peptides were exclusively recognized in patients bearing HLA-DRB1*0405. Furthermore, HLA-DRB1*0405-bearing patients, but not those with HLA-DRB1*15, recognized an increased breadth of melanocyte epitopes in comparison to HLA-matched control subjects (60% vs. 28%; P < 0.05). CONCLUSIONS: These data indicate that patients with VKH are sensitized to melanocyte epitopes and display a peptide-specific Th1 cytokine response. In addition, the data indicate that patients bearing HLA-DRB1*0405 recognize a broader melanocyte-derived peptide repertoire, reinforcing the importance of this allele in susceptibility to the development of VKH disease.

Adolescent↗

PubMedDate not supplied

Intermediate uveitis.

Intermediate uveitis is an intraocular inflammation involving the anterior vitreous, peripheral retina and pars plana. It usually affects patients from 5 to 30 years old, without gender or racial preferences. The etiology is unknown but there are several associated diseases: multiple sclerosis, idiopathic optic neuritis, autoimmune corneal endotheliopathy, sarcoidosis, thyroid diseases and inflammatory bowel diseases. Symptoms are blurry vision, floaters and distortion of central vision. The syndrome is bilateral in 80% of the patients and chronic with periods of exacerbation and remission. Clinical presentation includes: mild to moderate anterior chamber inflammation, thin keratic precipitates in the inferior portion of the cornea, autoimmune endotheliopathy, vitreitis, vasculitis in the peripheral retina, intravitreal "snowballs," retinal "snowbanking," optic neuritis and cystoid macular edema. Cataract and glaucoma are frequent complications. Treatment of intermediate uveitis is based on periocular and oral corticosteroids. Cryotherapy or laser photocoagulation of the peripheral retina are options in patients with snowbanking when there is an insufficient response to periocular or systemic corticosteroids. Imunosuppression may also be used when other therapies fail, and Cyclosporin A is the first drug of choice. Pars plana vitrectomy is indicated in patients with chronic significant inflammation, non-responsive cystoid macular edema, non-clearing vitreous hemorrhage, tractional retinal detachment and epiretinal membranes. The long-term prognosis of intermediate uveitis is usually good, particularly with strict control of inflammation and with proper management of complications. Patients can often maintain a vision of 20/50 or better.

Humans↗

PubMedDate not supplied

Ocular manifestations and treatment of syphilis.

Syphilis is a sexually transmitted, chronic, systemic infection caused by the spirochete Treponema pallidum. If left untreated, the disease progresses through four stages, with the potential to cause significant morbidity to any major organ of the body. Frequent syphilitic ocular manifestations, which can occur at any stage of the disease, include interstitial keratitis, anterior, intermediate, and posterior uveitis, chorioretinitis, retinitis, retinal vasculitis and cranial nerve and optic neuropathies. Diagnosis is centered around a high level of clinical suspicion and includes treponemal specific and non-treponemal serologic tests. All patients with newly diagnosed syphilis should be tested for co-infection with human immunodeficiency virus, as the risk factors are similar for both diseases. Additionally, all patients with ocular syphilis should be tested for neurosyphilis. The preferred treatment for all stages of syphilis remains parenteral penicillin G. With proper diagnosis and prompt antibiotic treatment, the majority of cases of syphilis can result in a cure.

Anti-Bacterial Agents↗

PubMedDate not supplied

Sympathetic ophthalmia.

Sympathetic ophthalmia is a rare, bilateral granulomatous uveitis that occurs after either surgical or accidental trauma to one eye. The ocular inflammation in the fellow eye becomes apparent usually within 3 months after injury. Clinical presentation is an insidious or acute anterior uveitis with mutton-fat keratic precipitates. The posterior segment manifests moderate to severe vitritis, usually accompanied by multiple yellowish-white choroidal lesions. Evidence suggests that sympathetic ophthalmia represents an autoimmune inflammatory response against choroidal melanocytes mediated by T cells. Diagnosis is based on clinical findings and a history of previous ocular trauma or surgery. Other causes of granulomatous uveitis, such as Vogt-Koyanagi-Harada disease, sarcoidosis, tuberculosis, and syphilis should be considered. Treatment of sympathetic ophthalmia consists of systemic anti-inflammatory agents with high dose oral corticosteroid as the drug of choice. However, if the inflammation cannot be controlled, cyclosporine is then used. Other immunosuppressive agents, such as chlorambucil, cyclophosphamide or azathioprine, may be necessary for the control of inflammation. The role of enucleation after the diagnosis of sympathetic ophthalmia remains controversial. Visual prognosis is reasonably good with prompt wound repair and appropriate immunomodulatory therapy.

Diagnosis, Differential↗

PubMedDate not supplied

Vogt-Koyanagi-Harada disease.

Vogt-Koyanagi-Harada disease (VKH) is a multisystem autoimmune disorder principally affecting pigmented tissues in the ocular, auditory, integumentary and central nervous systems. Patients are typically 20 to 50 years old and have no history of either surgical or accidental ocular trauma. Pigmented races are more commonly affected. Depending on revised diagnostic criteria, the disease is classified as complete, incomplete or probable based on the presence of extraocular findings (neurological, auditory and integumentary). The clinical course of VKH is divided into four phases: prodromal (mimics a viral infection), uveitic (bilateral diffuse uveitis with papillitis and exudative retinal detachment), convalescent (tissue depigmentation), and chronic recurrent (recurrent uveitis and ocular complications). The pathogenesis of VKH is thought to be related to an aberrant T cell-mediated immune response directed against self-antigens found on melanocytes. VKH has been linked to human leukocyte antigen DR4 (HLA-DR4) and HLA-Dw53, with strongest associated risk for HLA-DRB1*0405 haplotype. The diagnosis of VKH is clinical, and differential includes sympathetic ophthalmia, sarcoidosis, primary intraocular B-cell lymphoma, posterior scleritis, and uveal effusion syndrome. Treatment is typically initiated with high-dose oral corticosteroids, but other immunomondulatory agents (most oftentimes cyclosporine) may be needed for non-responsive patients or when corticosteroid side-effects are not tolerated. Visual prognosis is generally good with prompt diagnosis and aggressive immunomodulatory treatment.

Diagnosis, Differential↗

PubMedDate not supplied

Retinal toxicity of intravitreal triamcinolone acetonide: a morphological study.

PURPOSE: To evaluate the morphologic effects of intravitreal triamcinolone acetonide (TA) on rabbit retina. METHODS: Intravitreal injections of 0.5 mg, 1 mg, 4 mg, 8 mg, and 20 mg of TA (Kenalog-40; Bristol-Myers Squibb, Princeton, NJ) in 0.1 mL were given to pigmented rabbits. For control, 0.1 mL of TA vehicle and saline were injected. Animals were killed on day 14, and retinas were analyzed by light as well as electron microscopy. RESULTS: No ophthalmoscopic change was found. Eyes injected with 0.5 mg and 1 mg of TA did not have morphologic abnormality. Eyes injected with 4 mg, 8 mg, and 20 mg showed destruction of photoreceptor outer segments and migration of macrophage-like cells in the subretinal space. Eyes injected with 20 mg showed more extensive damage and increased pigment granules in the retinal pigment epithelium cells with large oil droplets in the cytoplasm. Electron microscopy also showed loss of photoreceptor/retinal pigment epithelium interdigitations. Eyes injected with vehicle or saline did not show morphologic changes. CONCLUSION: Single intravitreal injection of 0.5 mg or 1 mg of TA did not produce morphologic retinal changes in pigmented rabbits. However, injections of 4 mg, 8 mg, and 20 mg of TA produced outer retina toxic effects. These findings suggest that long-term retinal toxicity studies should be carried out, using single and repeated injections before this therapy becomes more widely used.

Animals↗