Long-term follow-up of patients with high-risk facial basal cell carcinoma treated with interferon.

BACKGROUND: Surgery is the treatment of choice for patients with basal cell carcinoma (BCC). When surgery is not a choice, only radiotherapy is recommended for patients with high-risk facial BCC. Interferon could be an acceptable therapeutic option for these patients. OBJECTIVE: To evaluate the long-term clinical response to interferon therapy in patients with high-risk facial BCC. METHODS: Patients with high-risk facial BCC were treated with perilesional injections of alpha-2b+ gamma interferons. Those with incomplete clinical response were reevaluated, their residual tumors excised, and declared cured. Patients treated with interferon and those treated with interferon plus surgery were followed for five years. Time to recurrence and the emergence of a new facial BCC were estimated by Kaplan-Meier survival analysis. Adverse events were documented. RESULTS: This study included 195 participants; 143 (73.3%) showed a complete response (95% CI 67.2‒80.1). Patients developed recurrence after a mean of 55 months (95% CI 53.8‒57.4). The estimated rate of recurrence was 12.3% (95% CI 7.4‒17.1). Patients developed a new BCC after a mean of 52.7 months (95% CI 50.4‒54.9). The estimated rate for development of a new BCC was 20.0% (95% CI 14.4‒25.9). Fifteen (7.7%) patients abandoned the study during follow-up. Adverse events were frequent but moderate or mild; fever and local pain were the most frequent. STUDY LIMITATIONS: Observational cohort design without a control group for comparison. CONCLUSIONS: Perilesional injections of alpha-2b+ gamma interferons in patients with facial high-risk BCC offer a satisfactory cure rate after five years of follow-up with an acceptable safety profile.

Long-term follow-up of patients with high-risk facial basal cell carcinoma treated with interferon

Abstract Background Surgery is the treatment of choice for patients with basal cell carcinoma (BCC). When surgery is not a choice, only radiotherapy is recommended for patients with high-risk facial BCC. Interferon could be an acceptable therapeutic option for these patients. Objective To evaluate the long-term clinical response to interferon therapy in patients with high-risk facial BCC. Methods Patients with high-risk facial BCC were treated with perilesional injections of alpha-2b+ gamma interferons. Those with incomplete clinical response were reevaluated, their residual tumors excised, and declared cured. Patients treated with interferon and those treated with interferon plus surgery were followed for five years. Time to recurrence and the emergence of a new facial BCC were estimated by Kaplan-Meier survival analysis. Adverse events were documented. Results This study included 195 participants; 143 (73.3%) showed a complete response (95% CI 67.2‒80.1). Patients developed recurrence after a mean of 55 months (95% CI 53.8‒57.4). The estimated rate of recurrence was 12.3% (95% CI 7.4‒17.1). Patients developed a new BCC after a mean of 52.7 months (95% CI 50.4‒54.9). The estimated rate for development of a new BCC was 20.0% (95% CI 14.4‒25.9). Fifteen (7.7%) patients abandoned the study during follow-up. Adverse events were frequent but moderate or mild; fever and local pain were the most frequent. Study limitations Observational cohort design without a control group for comparison. Conclusions Perilesional injections of alpha-2b+ gamma interferons in patients with facial high-risk BCC offer a satisfactory cure rate after five years of follow-up with an acceptable safety profile.

Validation of Two-Tiered Enzyme-Linked Immunosorbent Assay for the Detection of Anti-HeberProt-P® Antibodies

Heberprot-P® is a therapeutic product approved in Cuba for the treatment of diabetic foot ulcer. In spite of its ample clinical use, its immunogenicity in patients has not been evaluated. Regulatory agencies have developed guidelines for the validation of immunoassays designed at the detection of anti-drug antibodies to biologicals. The aim on this work was to validate a method for the detection of binding antibodies in human serum to recombinant human epider-mal growth factor (rhEGF), the active ingredient of Heberprot-P®. A two-tiered enzyme-linked immunosorbent assay (ELISA) format was used. First tier was a screening assay, based on im-mobilized rhEGF and anti-human polyvalent alkaline-phosphatase conjugated as development reagent. Positive samples were then tested with a confirmatory assay which used a competitive soluble rhEGF in solution. As FDA and EMA guidelines recommend, minimum required dilution, quality controls, screening and confirmatory cut points, sensitivity, recovery, precision, speci-ficity, selectivity, robustness and stability of samples were determined. The assay was precise and its sensitivity was calculated to be 214.2 ng/mL. The majority of evaluated parameters fulfilled the figures recommended by current guidelines. The immunoassays described in this work could be reliable tools for the evaluation of immunogenicity of Heberprot-P® in well-de-signed clinical studies (AU)

Demencia frontotemporal luego de un evento vital. Presentación de un caso / Frontotemporal dementia after a stressful life event. A case report

Fundamento: La demencia frontotemporal es un trastorno degenerativo caracterizado por disturbios cognitivos o del comportamiento debido a la atrofia de los lóbulos frontales y temporales anteriores. No se han descrito casos que ocurran a partir de un evento vital estresante. Objetivo: Presentar un paciente con demencia frontotemporal que debuta después de un evento vital y que implica una peculiaridad para el diagnóstico y el manejo de estos pacientes así como para la posible relación causal. Presentación del caso: Paciente de 47 años con antecedentes de salud anterior y no antecedentes familiares de demencia o trastornos neurológicos que, inmediatamente después de un evento vital como lo fue la muerte de su hijo, desarrolla síntomas compatibles con una psicosis aguda y una depresión asociados a profundos trastornos de la conducta y del lenguaje típicos de una demencia frontotemporal. Las imágenes de resonancia magnética nuclear confirmaron la atrofia frontotemporal. Trascurrieron menos de dos años desde el primer síntoma hasta el diagnostico de la demencia. Conclusiones: A pesar de las evidencias morfológicas y epidemiológicas en contra, la posible relación causal entre los eventos vitales estresantes y el desarrollo ulterior de una demencia no deben descartarse.

Background: Frontotemporal dementia is a degenerative disorder characterized by atrophy of frontal and anterior parietal lobes. Cases of frontotemporal dementia that occur after a stressful life event have not been described. Objective: To present a case of frontotemporal dementia that took place after a stressful life event and implies a peculiarity for diagnosis and management of these patients and for the causal relationship. Case report: A 47 year-old male, previously healthy, and without a family history of dementia or neurological diseases, immediately after a stressful life event such as the death of his son, developed symptoms compatible with an acute psychosis or depression associated with severe behavioral and language disorders typical of a frontotemporal dementia. Magnetic Resonance Imaging study confirmed the diagnosis of frontotemporal dementia. Less than two years passed from the first symptom until the diagnosis of dementia. Conclusions: In spite of morphological and epidemiological evidences against, the possible causal relation between the stressful life events and the onset of dementias can not be ruled out and deserve a deeper study.

Demencia frontotemporal luego de un evento vital: presentación de un caso / Frontotemporal dementia after a stressful life event: a case report

La demencia frontotemporal es un trastorno degenerativo caracterizado por disturbios cognitivos o del comportamiento debido a la atrofia de los lóbulos frontales y temporales anteriores. No se han descrito casos que ocurran a partir de un evento vital estresante. Objetivo: Presentar un paciente con demencia frontotemporal que debuta después de un evento vital y que implica una peculiaridad para el diagnóstico y el manejo de estos pacientes así como para la posible relación causal. Presentación del caso: Paciente de 47 años con antecedentes de salud anterior y no antecedentes familiares de demencia o trastornos neurológicos que, inmediatamente después de un evento vital como lo fue la muerte de su hijo, desarrolla síntomas compatibles con una psicosis aguda y una depresión asociados a profundos trastornos de la conducta y del lenguaje típicos de una demencia frontotemporal. Las imágenes de resonancia magnética nuclear confirmaron la atrofia frontotemporal. Trascurrieron menos de dos años desde el primer síntoma hasta el diagnostico de la demencia. Conclusiones: A pesar de las evidencias morfológicas y epidemiológicas en contra, la posible relación causal entre los eventos vitales estresantes y el desarrollo ulterior de una demencia no deben descartarse(AU)

Frontotemporal dementia is a degenerative disorder characterized by atrophy of frontal and anterior parietal lobes. Cases of frontotemporal dementia that occur after a stressful life event have not been described. Objective: To present a case of frontotemporal dementia that took place after a stressful life event and implies a peculiarity for diagnosis and management of these patients and for the causal relationship. Case report: A 47 year-old male, previously healthy, and without a family history of dementia or neurological diseases, immediately after a stressful life event such as the death of his son, developed symptoms compatible with an acute psychosis or depression associated with severe behavioral and language disorders typical of a frontotemporal dementia. Magnetic Resonance Imaging study confirmed the diagnosis of frontotemporal dementia. Less than two years passed from the first symptom until the diagnosis of dementia. Conclusions: In spite of morphological and epidemiological evidences against, the possible causal relation between the stressful life events and the onset of dementias can not be ruled out and deserve a deeper study(AU)

Oral manifestations of HIV infection in adult patients from the province of Sancti Spiritus, Cuba.

BACKGROUND: Studies on the prevalence of HIV-related oral lesions (HIV-OL) have shown great variations among different countries. The aim of this study was to describe the prevalence of HIV-OL in adults infected with HIV in the province of Sancti Spiritus, Cuba, and to determine the factors associated with the presence of HIV-OL. METHODS: A cross-sectional observational study was performed between November 2006 and August 2007 at the Hospital General Universitario 'Camilo Cienfuegos', Sancti Spiritus. One hundred and fifty-four HIV-infected patients were included. Patients were examined and interviewed by a periodontal specialist. Diagnosis of HIV-OL was based on clinical criteria. Demographical, clinical and laboratory data were obtained. Independent association of each factor with HIV-OL was assessed by logistic regression modelling. RESULTS: The prevalence of HIV-OL was 40.9%. The commonest manifestation was oral hairy leucoplakia (n = 19; 12.3%); oral candidiasis (n = 17; 11%); herpes simplex virus infection (n = 11; 7.4%); and aphthous ulcer (n = 9; 5.8%). Principal factors associated with the presence of HIV-OL were CD4(+) lymphocytes <500 cells/mm(3) (OR: 2.06; 95% CI: 1.019-4.195) and smoking (OR: 2.03 CI: 1.037-3.982). CONCLUSION: This study described the prevalence of HIV-OL in 154 HIV-infected patients which represent about 80% of those known to be infected in the province of Sancti Spiritus. The prevalence of HIV-OL was lower than those reported from developing countries. Oral hairy leucoplakia and oral candidiasis were the most prevalent HIV-OL. Smoking and CD4(+) cells count <500 cells/mm(3) were the two factors independently associated with the presence of HIV-OL.

Signalling via CD70, a member of the TNF family, regulates T cell functions.

In the present work, we provide data supporting that CD70, a tumor necrosis factor (TNF)-related molecule, defined as the CD27 ligand (CD27L), may actively regulate T cell functions similarly to other members of the TNF family (i.e., CD40L and CD30L). Cross-linking CD70 with specific monoclonal antibodies (mAb) stimulated cytotoxicity and cytokine production in human T cell clones. Detection of intracellular-free calcium mobilization and mitogen-activated protein kinase phosphorylation upon mAb engagement of CD70 further supported an active signaling role for the TNF-related molecule. Similar results were obtained in the Jurkat leukaemia T cell line stably transfected with CD70; in that system, induction of Akt phosphorylation was detected, indirectly revealing the involvement of the phosphatidylinositol-3 kinase pathway. Stimulation of CD70+ Jurkat cells, with a CD70-specific mAb or with COS-7 cells transiently transfected with CD27, induced transcriptional activity detectable by different reporter gene expression systems. Altogether, our data point out that a reciprocal communication may be established between CD27+ and CD70+ cells during the immune response.

Aggregation of MHC class I molecules on a CD8+ alphabeta T cell clone specifically inhibits non-antigen-specific lysis of target cells.

MHC class I molecules are target molecules recognized by TCR or NK receptors encoded in the NK gene cluster or leukocyte receptor cluster. We show that aggregation of MHC class I molecules by specific monoclonal antibodies on cytotoxic T cells, inhibits the anti-CD94 redirected lysis of P815. This inhibition is not the consequence of apoptosis or anergy of the cytotoxic T lymphocytes. In contrast, aggregation of MHC class I molecules does not inhibit either the anti-CD3 redirected cytotoxicity or the CD94-triggered up-regulation of CD25 molecules of the same T cell clone. MHC class I ligand molecules expressed by antigen presenting cells and/or T lymphocytes could therefore be able to modulate nonspecific cytotoxicity upon interaction with MHC class I molecules expressed by effector cytotoxic T lymphocytes.