Pemphigus herpetiformis: analysis of the autoantibody profile during the disease course with changes in the clinical phenotype

Pemphigus herpetiformis (PH) is a rare dapsone-responsive variant of pemphigus, characterized by annular and vesiculopustular cutaneous lesions. Most PH serum samples contain autoantibodies against desmoglein (Dsg)1, but not Dsg3, and the presence of the latter is almost invariably associated with mucosal involvement, as predicted based on the 'Dsg compensation theory'. We describe a patient with features characteristic of PH with histologically eosinophilic spongiosis who repeatedly tested positive for anti-Dsg3 but not anti-Dsg1 autoantibodies by ELISA. To investigate whether the peculiar clinical phenotype was due to a distinct immunological profile, the patient's serum was tested by ELISA and immunoblotting using recombinant forms of Dsg3. Serum samples were found to have low and high reactivity against the EC1 and the EC4 domains of Dsg3, respectively, whereas the autoantibodies belonged predominantly to the IgG1 and IgG4 subclasses. The overall immunological profile was typical of pemphigus vulgaris. The patient finally developed isolated oral erosions 22 months after initial presentation, without significant changes in the autoantibody profile and of the targeted antigenic sites. Our patient presented features characteristic of PH. Although circulating anti-Dsg3 antibodies were present, the patient had only cutaneous involvement for a long period. Our findings indicate that the proposed Dsg compensation theory cannot always explain the clinical phenotype, changes in which may occur without apparent modification of the autoantibody profile and antibody specificity. Hence, additional factors, such as Fcgamma-dependent neutrophil activation, may critically affect the clinical presentation of pemphigus.

In vitro detection of cytotoxic T and NK cells in peripheral blood of patients with various drug-induced skin diseases

BACKGROUND: Cytotoxic cells are involved in most forms of drug-induced skin diseases. Till now, no in vitro test addressed this aspect of drug-allergic responses. Our report evaluates whether drug-induced cytotoxic cells can be detected in peripheral blood of nonacute patients with different forms of drug hypersensitivity, and also whether in vitro detection of these cells could be helpful in drug-allergy diagnosis. METHODS: GranzymeB enzyme-linked immunosorbent spot-forming (ELISPOT) and cell surface expression of the degranulation marker CD107a were evaluated on peripheral blood mononuclear cells from 12 drug-allergic patients in remission state and 16 drug-exposed healthy controls. RESULTS: In 10/12 allergic patients culprit but not irrelevant drug elicited granzymeB release after 48-72 h stimulation. It was clearly positive in patients with high proliferative response to the drug, measured in lymphocyte transformation tests. In patients, who showed moderate or low proliferation and low drug-response in granzymeB ELISPOT, overnight preincubation with interleukin (IL)-7/IL-15 enhanced drug-specific granzymeB release and allowed to clearly identify the offending agent. CD107a staining was positive on CD4+/CD3+, CD8+/CD3+ T cells as well as CD56+/CD3- natural killer cells. None of the drug-exposed healthy donors reacted to the tested drugs and allergic patients reacted only to the offending, but not to tolerated drugs. CONCLUSION: GranzymeB ELISPOT is a highly specific in vitro method to detect drug-reacting cytotoxic cells in peripheral blood of drug-allergic patients even several years after disease manifestation. Together with IL-7/IL-15 preincubation, it may be helpful in indentifying the offending drug even in some patients with weak proliferative drug-response.

Position paper on diagnosis and treatment of atopic dermatitis

The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease.

A cross cultural study of vaginal practices and sexuality: Implications for sexual health

Between 2005 and 2006, we investigated vaginal practices in Yogyakarta, Indonesia; Tete, Mozambique; KwaZulu-Natal, South Africa; and Bangkok and Chonburi, Thailand. We sought to understand women's practices, their motivations for use and the role vaginal practices play in women's health, sexuality and sense of wellbeing. The study was carried out among adult women and men who were identified as using, having knowledge or being involved in trade in products. Further contacts were made using snowball sampling. Across the sites, individual interviews were conducted with 229 people and 265 others participated in focus group discussions. We found that women in all four countries have a variety of reasons for carrying out vaginal practices whose aim is to not simply 'dry' the vagina but rather decrease moisture that may have other associated meanings, and that they are exclusively "intravaginal" in operation. Practices, products and frequency vary. Motivations generally relate to personal hygiene, genital health or sexuality. Hygiene practices involve external washing and intravaginal cleansing or douching and ingestion of substances. Health practices include intravaginal cleansing, traditional cutting, insertion of herbal preparations, and application of substances to soothe irritated vaginal tissue. Practices related to sexuality can involve any of these practices with specific products that warm, dry, and/or tighten the vagina to increase pleasure for the man and sometimes for the woman. Hygiene and health are expressions of femininity connected to sexuality even if not always explicitly expressed as such. We found their effects may have unexpected and even undesired consequences. This study demonstrates that women in the four countries actively use a variety of practices to achieve a desired vaginal state. The results provide the basis for a classification framework that can be used for future study of this complex topic.

Coronary collateral growth by external counterpulsation: a randomised controlled trial

The efficacy of external counterpulsation (ECP) on coronary collateral growth has not been investigated in a randomised controlled study. Objective To test the hypothesis that ECP augments collateral function during a 1 min coronary balloon occlusion.

Percutaneous access of the epicardial space for mapping ventricular and supraventricular arrhythmias in patients with and without prior cardiac surgery

There is a paucity of data on the success rates of achieving percutaneous epicardial access in different groups of patients.

Brugada syndrome ECG provoked by the selective serotonin reuptake inhibitor fluvoxamine

A patient with an SCN5A p.W822X nonsense mutation, localized in the transmembrane region DII-S4 of the Na(v)1.5 sodium channel and leading to a non-expression of the mutant allele, was prescribed the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (Floxyfral), 100 mg per day. His normal baseline ECG changed to a characteristic Brugada-Type-1-ECG pattern. To investigate whether fluvoxamine may reduce the cardiac sodium current, the effect of this drug was studied on the wild-type voltage-gated cardiac sodium channel Na(v)1.5 stably expressed in HEK293 cells. Patch-clamp recording showed a 50% inhibition of the current at a concentration of 57.3 microM. In our patient, no arrhythmia occurred but the proarrhythmic potential of SSRI in patients with SCN5A mutations cannot be excluded. Therefore, we advise 12-lead ECG control after administering SSRI in these patients.

Association Between Posttraumatic Stress Disorder Following Myocardial Infarction and Liver Enzyme Levels: A Prospective Study

Research in rodents demonstrated that psychological stress increases circulating levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase reflecting liver injury. Moreover, chronic posttraumatic stress disorder and transaminases predicted coronary heart disease.

Early 4-Week Cardiac Rehabilitation Exercise Training in Elderly Patients After Heart Surgery

The aim of this study was to assess the effects on exercise performance of supplementing a standard cardiac rehabilitation program with additional exercise programming compared to the standard cardiac rehabilitation program alone in elderly patients after heart surgery.

Inflammatory Biomarkers in Patients with Posttraumatic Stress Disorder Caused by Myocardial Infarction and the Role of Depressive Symptoms

Inflammation might link posttraumatic stress disorder (PTSD) with an increased risk of cardiovascular events. We explored the association between PTSD and inflammatory biomarkers related to cardiovascular morbidity and the role of co-morbid depressive symptoms in this relationship.

Stress hormones in patients with posttraumatic stress disorder caused by myocardial infarction and role of comorbid depression

Chronic posttraumatic stress disorder (PTSD) has been associated with perturbed hypothalamic-pituitary-adrenal (HPA) axis function and a hyperadrenergic state. We hypothesized that patients with PTSD attributable to myocardial infarction (MI) would show peripheral hypocortisolemia and increased norepinephrine levels, whereby taking into account that depressive symptoms would affect this relationship.

Fine particulate matter measurements in Swiss restaurants, cafés and bars: what is the effect of spatial separation between smoking and non-smoking areas?

We performed 124 measurements of particulate matter (PM(2.5)) in 95 hospitality venues such as restaurants, bars, cafés, and a disco, which had differing smoking regulations. We evaluated the impact of spatial separation between smoking and non-smoking areas on mean PM(2.5) concentration, taking relevant characteristics of the venue, such as the type of ventilation or the presence of additional PM(2.5) sources, into account. We differentiated five smoking environments: (i) completely smoke-free location, (ii) non-smoking room spatially separated from a smoking room, (iii) non-smoking area with a smoking area located in the same room, (iv) smoking area with a non-smoking area located in the same room, and (v) smoking location which could be either a room where smoking was allowed that was spatially separated from non-smoking room or a hospitality venue without smoking restriction. In these five groups, the geometric mean PM(2.5) levels were (i) 20.4, (ii) 43.9, (iii) 71.9, (iv) 110.4, and (v) 110.3 microg/m(3), respectively. This study showed that even if non-smoking and smoking areas were spatially separated into two rooms, geometric mean PM(2.5) levels in non-smoking rooms were considerably higher than in completely smoke-free hospitality venues. PRACTICAL IMPLICATIONS: PM(2.5) levels are considerably increased in the non-smoking area if smoking is allowed anywhere in the same location. Even locating the smoking area in another room resulted in a more than doubling of the PM(2.5) levels in the non-smoking room compared with venues where smoking was not allowed at all. In practice, spatial separation of rooms where smoking is allowed does not prevent exposure to environmental tobacco smoke in nearby non-smoking areas.

How to assess the external validity of therapeutic trials: a conceptual approach

Background External validity of study results is an important issue from a clinical point of view. From a methodological point of view, however, the concept of external validity is more complex than it seems to be at first glance. Methods Methodological review to address the concept of external validity. Results External validity refers to the question whether results are generalizable to persons other than the population in the original study. The only formal way to establish the external validity would be to repeat the study for that specific target population. We propose a three-way approach for assessing the external validity for specified target populations. (i) The study population might not be representative for the eligibility criteria that were intended. It should be addressed whether the study population differs from the intended source population with respect to characteristics that influence outcome. (ii) The target population will, by definition, differ from the study population with respect to geographical, temporal and ethnical conditions. Pondering external validity means asking the question whether these differences may influence study results. (iii) It should be assessed whether the study's conclusions can be generalized to target populations that do not meet all the eligibility criteria. Conclusion Judging the external validity of study results cannot be done by applying given eligibility criteria to a single target population. Rather, it is a complex reflection in which prior knowledge, statistical considerations, biological plausibility and eligibility criteria all have place.