Circulating platelet aggregates: a chronic platelet activation in patients with transient ischaemic attacks

Platelet hyperaggregability was tested in 62 TIA patients by means of the formalin fixing principle of Wu and Hoak. Compared to age-matched controls, the platelet aggregates ratio (PAR) was reduced from 0.99±0.04 SD to 0.807±0.14 SD. This means a highly significant increase of circulating platelet aggregates (CPA) in untreated TIA patients, regardless of the interval sinche the last attack (from 2 days to 1 year). PAR was especially reduced in patients with abnormal angiography (expressing pronounced cerebral or diffuse ATS) and it was possibly affected by previous antiplatelet treatment with ASA. Supported by the National Research Council, Special Project on Preventive Medicine.     

Effect of amantadine on drug-induced parkisonism: relationship between plasma levels and effect.

Amantadine, administered at a dose of 200 mg/day, antagonized the extapyramidal symptomatology induced by neuroleptic drugs in fifteen psychiatric patients. Steady-state levels were reached within 4-7 days of treatment. Individual plasma levels ranged from 200-900 ng/ml. Apparent plasma half-lives varied from 10-28.5 h with an apparent VD of 200-400 litres. A significant relationship was found between the plasma levels of amantadine and the effects on the extrapyramidal symptomatology. The data suggest a direct effect of amantadine on dopaminergic receptors.     

Presentation of a system for computer-aided decision in diabetes therapeutics

This paper presents Sphinx, an expert system for computer-aided diagnosis in diabetes therapeutic. This interactive program makes logic deductions, comprehensible for users and it is not necessary for them to know artificial intelligence methodology. An improvement of the first results is possible and necessary, but the reliability of the advice already expressed by the system makes it useful as a future physician's implement.     

Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell trans-infection

Cytomegalovirus (CMV) infection is characterized by host immunosuppression and multiorganic involvement. CMV-infected dendritic cells (DC) were recently shown to display reduced immune functions, but their role in virus dissemination is not clear. In this report, we demonstrated that CMV could be captured by DC through binding on DC-SIGN and subsequently transmitted to permissive cells. Moreover, blocking DC-SIGN by specific antibodies inhibited DC infection by primary CMV isolates and expression of DC-SIGN or its homolog DC-SIGNR rendered susceptible cells permissive to CMV infection. We demonstrated that CMV envelope glycoprotein B is a viral ligand for DC-SIGN and DC-SIGNR. These results provide new insights into the molecular interactions contributing to cell infection by CMV and extend DC-SIGN implication in virus propagation.     

From idiopathic infectious diseases to novel primary immunodeficiencies

Primary immunodeficiencies are typically seen as rare monogenic conditions associated with detectable immunologic abnormalities, resulting in a broad susceptibility to multiple and recurrent infections caused by weakly pathogenic and more virulent microorganisms. By opposition to these conventional primary immunodeficiencies, we describe nonconventional primary immunodeficiencies as Mendelian conditions manifesting in otherwise healthy patients as a narrow susceptibility to infections, recurrent or otherwise, caused by weakly pathogenic or more virulent microbes. Conventional primary immunodeficiencies are suspected on the basis of a rare, striking, clinical phenotype and are defined on the basis of an overt immunologic phenotype, often leading to identification of the disease-causing gene. Nonconventional primary immunodeficiencies are defined on the basis of a more common and less marked clinical phenotype, which remains isolated until molecular cloning of the causal gene reveals a hitherto undetected immunologic phenotype. Similar concepts can be applied to primary immunodeficiencies presenting other clinical features, such as allergy and autoimmunity. Nonconventional primary immunodeficiencies thus expand the clinical boundaries of this group of inherited disorders considerably, suggesting that Mendelian primary immunodeficiencies are more common in the general population than previously thought and might affect children with a single infectious, allergic, or autoimmune disease.     

Granulomatous disease in common variable immunodeficiency

PURPOSE: Common variable immunodeficiency (CVID), defined by defective production of immunoglobulins, is the most common primary immunodeficiency in adulthood requiring a medical follow-up. Repeated bacterial infections and/or autoimmune manifestations and/or benign lymphoproliferation (including follicular hyperplasia and/or granulomatous disease) are the hallmark of the disease. This review aims at describing recent advances in the understanding and treatment of granulomatous disease in CVID. CURRENT KNOWLEDGE AND KEY POINTS: Clinical features of granulomatous disease in CVID can mimic sarcoidosis, remarkable by the low levels of circulating immunoglobulins. Granulomas may be found in several organs in a single patient, and the main features are pulmonary, lymphoid, cutaneous, hepatic or splenic. The features of CVID is remarkable by the high frequency of autoimmune diseases complicating the immunodeficiency. Some immunological abnormalities have been described in such patients, including lymphopenia, decreased T-cells proliferations to mitogens and antigens. Rare polymorphisms in the gene encoding TNFalpha (Tumor Necrosis Factor) have been identified in CVID patients with granulomatous disease. FUTURE PROSPECTS AND PROJECTS: The evolution of the disease is severe, particularly when the lung is involved. Treatment consists in immunoglobulins substitution, immunosuppressive agents (corticosteroids, cyclophosphamide) and anti-TNFalpha antibodies. These treatments are difficult to manage in such immunocompromised patients.     

18F-fluorodeoxyglucose positron emission tomography/computed tomography in AIDS-related Burkitt lymphoma

This study aims to describe 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) findings in patients with AIDS-related Burkitt lymphoma, at various times of treatment, and to define its utility for a better patient management. We retrospectively studied 13 consecutive HIV-positive patients with Burkitt lymphoma who underwent one or more PET/CT. In 5 of 5 patients imaged before treatment, PET/CT confirmed all involved sites detected at conventional work-up and demonstrated additional sites in 4 of 5 patients. Lymph node involvement, which is known to be uncommon in endemic or sporadic Burkitt lymphoma, was present in 54% of patients. Additionally, in 3 patients, Burkitt lymphoma was predominantly located in parotid lymph nodes, which is also an unusual finding. A negative scan was encountered in 3 of 10 patients imaged during treatment and in 1 of 4 patients imaged after treatment completion and was always associated with lasting complete remission. Presence of residual area of uptake was related to both favorable and unfavorable outcome whether performed during treatment (5/7 and 2/7, respectively) or after (1/3 and 2/3, respectively). Areas of increased uptake could be observed in lung (4 cases) or esophagus (3 cases), and were clinically related to pneumonia or esophagitis. We recommend PET/CT for accurate initial staging of patients with AIDS-related Burkitt lymphoma. PET/CT is also useful to monitor treatment response, as regression of initial disease can be early observed. Furthermore, PET/CT appears to have prognostic value, as a negative scan was always associated with a favorable outcome.