Antigen-specific therapies in multiple sclerosis

During recent years, many new therapies for human autoimmune diseases such as multiple sclerosis (MS) have been considered based on promising in vitro data or animal experiments. A number of them have proceeded to early clinical testing. However, very few finally advanced to approval by the regulatory agencies and are currently available to patients. The main reasons for failure were either lack of efficacy in humans and/or unexpected and untolerable adverse events. Although previous attempts toward antigen-specific immunomodulation have often been disappointing, these difficulties have led to renewed interest in therapies that aim at reestablishing tolerance to autoantigens at the level of either T cell-mediated or antibody-mediated immune responses or both. Such antigen-specific immunotherapies offer the prospect of correcting pathological immune reactivity against autoantigens in a highly specific and effective manner and also achievement of this goal with relatively little side effects. Here we will review the various approaches that are currently being considered for antigen-specific immunotherapies in MS.     

Are there clinical or serological differences between male and female patients with primary Sjögren's syndrome?

OBJECTIVE: Sj?gren's syndrome (SS) is a chronic inflammatory autoimmune disease. It can be primary (pSS) or secondary (sSS) and is observed 90% more in women than in men, mainly in the fourth and fifth decades of life. We investigated the prevalence of serological and clinical manifestations in male and female patients with primary SS. METHODS: We analyzed 521 female and 28 male patients with pSS between 1993 and 2001. All patients fulfilled > or = 4 of the 1993 European Community Study Group criteria. RESULTS: Men presented higher concentrations of IgA, rheumatoid factor, and antinuclear antibodies than women. A higher percentage of women than men reported fibromyalgia, thyroidal manifestations, and carpal tunnel syndrome. There were no statistical differences between the 2 groups in relation to the presence of Raynaud's phenomenon, arthritis, erosive osteoarthritis, liver disease, or other visceral manifestations. CONCLUSION: The pattern of SS in our cohort of patients reveals a difference between male and female patients, in contrast with earlier studies.     

Nasal Inspiratory Pressure: an Alternative for the Assessment of Inspiratory Muscle Strength?

IntroductionInspiratory muscle strength is usually assessed thorough the determination of static mouth pressure (PImax). However, since this manoeuvre presents certain problems, alternative techniques have been developed over the last few years. One of the most promising is determination of sniff nasal inspiratory pressure (SNIP).AimTo evaluate SNIP assessment as an alternative for the evaluation of the inspiratory muscle strength.MethodsSubjects were consecutively included and assigned to one of three different groups: control (8), COPD patients (23) and patients with neuromuscular disorders (21). Different maximal inspiratory pressures were determined: (a) dynamic in the esophagus (maximal sniff Pes, reference variable), (b) PImax, and (c) SNIP.ResultsBoth SNIP and MIP showed an excellent correlation with Pes (r=0.835 and 0.752, respectively, P<0.05 for both). SNIP/Pes intra-class correlation coefficients were 0.585 (CI 95%: ?0.097 to 0.901) in controls, 0.569 (CI 95%: ?0.048 to 0.836) in COPD patients, and 0.840 (CI 95%: 0.459 to 0.943) in neuromuscular disorders, respectively. For PImax/Pes, these values were 0.602 CI 95%: ?0.108 to 0.933), 0.418 (CI 95%: ?0.108 to 0.761), and 0.712 (CI 95%: 0.378 a 0.882). Moreover, both SNIP and PImax showed 100% sensitivity in the three groups of subjects, although specificities were 100%, 69% and 75% for SNIP, and 83%, 54% and 75% for PImax, respectively.ConclusionsSNIP is a good physiological marker of inspiratory muscle strength. Its role is likely to complement that of PImax.     

Failure to perform index cholecystectomy during acute cholecystitis results in significant morbidity for patients who present with recurrence

BackgroundAlthough index cholecystectomy is considered the treatment of choice for acute cholecystitis (AC), many hospital systems struggle to provide such a service. The aim of this study was to analyze the effect of failure to perform index cholecystectomy in patients presenting with acute cholecystitis.MethodsBetween June 2010 and December 2015, all patients presenting to one hospital with an initial attack of AC were enrolled into a prospective database. Patient's records were reviewed up until point of delayed cholecystectomy or for a minimum of 24 months after the initial presentation with AC. Recurrent AC was defined as early (<6 weeks from initial discharge) or late (>6 weeks from initial discharge).ResultsIn total 998 patients presented with AC, 409 (41%) of whom were discharged without index cholecystectomy. Eighty-three (20%) patients presented with AC recurrence (ACR). Compared to the first AC episode, patients were more likely to present with grade III AC and suffer significantly greater morbidity (p < 0.05 for all comparisons). A prior history of biliary disease was associated with ACR (p = 0.002). ACR occurred early in 48 (58%) patients and delayed in 35 (42%) patients.ConclusionsTwenty percent of patients discharged without cholecystectomy after their first attack of ACR will develop recurrence within the first two years. Half of ACR will occur within 6 weeks. Patients who present with ACR are more likely to develop more severe AC and are likely to suffer greater morbidity as compared to their first attack.     

Dynamics of T cells subsets and lymphoproliferative responses during structured treatment interruption cycles and after definitive interruption of HAART in early chronic HIV type-1-infected patients

Little is known about the consequences of short cycles of structured treatment interruption or definitive interruption of HAART for both T cell subset dynamics and T lymphoproliferative responses (LPR). Immunological follow-up was performed in 45 early chronical HIV-1-infected patients during short STI cycles during the first 12 weeks after the definitive interruption of HAART (DTI) and, thereafter, until VL reached a plateau. During STI cycles, CD8(+), CD8(+), CD28(+), activation markers and naive CD4(+) T cells increased significantly (p < 0.0001), while both naive CD8(+) and memory CD4(+) T cells decreased. During DTI, CD8(+) CD28(+) T cells fell and CD4(+) naive T cells stabilized and the rest of the T cell subsets presented changes similar to those during STI cycles. Despite a transient increase in LPR to recall antigens and HIV proteins during STI cycles, LPR to polyclonal stimuli and pathogens decreased over the study. Differences in T cell subset dynamics and LPR observed throughout the study suggest that multiple exposures to low levels of antigen could improve the immune system, mainly by driving T cell maturation. Conversely, higher and longer viral replication after cessation of HAART overwhelms the immune system. These data may help to guide future immune-based therapies.     

Transmission of HIV-1 from an obstetrician to a patient during a caesarean section

We describe a probable case of HIV-1 transmission from a healthcare worker (HCW) to a patient during a caesarean section. Genetic distance comparisons of the viral sequence of the C2V4 region of the viruses from the patient and the obstetrician showed an average nucleotide sequence divergence of 3% (2.8-3.1). HIV can be transmitted from an infected HCW to a patient when percutaneous injuries with subsequent exposure of the patient to the blood of the HCW can occur.