Thrombolysis with recombinant human tissue-type plasminogen activator during instability in coronary artery disease: effect on myocardial ischemia and need for coronary revascularization. TRIC Study Group.

Two hundred five men, 40 to 70 years of age, admitted to the coronary care unit with unstable coronary artery disease (unstable angina or non-Q wave myocardial infarction), were randomized to double-blind placebo-controlled treatment with an intravenous infusion of recombinant tissue-type plasminogen activator (rTPA), 1 mg/kg body weight (maximum 100 mg) during 4 hours, in addition to aspirin, heparin, and beta-blockade. No severe complications occurred. Myocardial ischemia, defined as myocardial infarction, incapacitating angina despite medication, or signs of ischemia at the exercise test, was reduced by treatment with rTPA compared with placebo both at discharge, 53% compared with 70% (p = 0.02), and at 1 month, 61% compared with 80% (p = 0.005). Signs of myocardial ischemia during the exercise test were reduced at discharge 51.0% compared with 68% (p = 0.03) and at 1 month 48% compared with 62% (p = 0.09). Coronary angiography after 1 month showed no difference in major coronary lesions between the groups, nor was there any reduction in the number of performed coronary revascularization procedures. In conclusion, treatment with rTPA in unstable coronary artery disease in men reduced myocardial ischemia but did not significantly reduce the need for revascularization in long-term follow-up.     

Occurrence of apoptosis, secondary necrosis, and cytolysis in eosinophilic nasal polyps

The paradigm states that inflammatory cells disappear from airway tissues through apoptosis and phagocytosis. However, cells may also be cleared through primary cytolysis, necrosis secondary to apoptosis, or transepithelial migration. This study examines the occurrence of apoptosis, secondary necrosis, and cytolysis of eosinophils in human nasal polyps in vivo and blood eosinophils in vitro. Eosinophils abounded in subepithelium and in paracellular epithelial pathways. Macrophages commonly occurred but without engulfed eosinophils. Scattered cells, including epithelial cells, were stained by antibody to the caspase cleavage product of poly(ADP-ribose) polymerase. Few cells were apoptotic (stained by terminal deoxy RNase nick end labeling). Of more than 3,000 examined tissue eosinophils, 110 were caspase cleavage positive, but only one was apoptotic. Transmission electron microscopy analysis of more than 500 eosinophils revealed viable and cytolytic eosinophils but not apoptosis, secondary necrosis, or engulfment of eosinophils. Plasma cells but neither epithelial cells nor eosinophils exhibited apoptotic ultrastructural morphology. Eosinophils in vitro exhibited different stages of apoptosis, ending with secondary necrosis distinct from in vivo eosinophil cytolysis. Our results show that the clearance of eosinophils from nasal polyps largely occurs through nonapoptosis pathways, including cytolysis and paraepithelial migration, and they challenge the belief that apoptosis is important for clearance of eosinophils from respiratory tissues.     

A Phenotypic Approach for IUIS PID Classification and Diagnosis: Guidelines for Clinicians at the Bedside

The number of genetically defined Primary Immunodeficiency Diseases (PID) has increased exponentially, especially in the past decade. The biennial classification published by the IUIS PID expert committee is therefore quickly expanding, providing valuable information regarding the disease-causing genotypes, the immunological anomalies, and the associated clinical features of PIDs. These are grouped in eight, somewhat overlapping, categories of immune dysfunction. However, based on this immunological classification, the diagnosis of a specific PID from the clinician’s observation of an individual clinical and/or immunological phenotype remains difficult, especially for non-PID specialists. The purpose of this work is to suggest a phenotypic classification that forms the basis for diagnostic trees, leading the physician to particular groups of PIDs, starting from clinical features and combining routine immunological investigations along the way. We present 8 colored diagnostic figures that correspond to the 8 PID groups in the IUIS Classification, including all the PIDs cited in the 2011 update of the IUIS classification and most of those reported since.     

Lower limb motor restlessness in Asperger's disorder, measured using actometry

The movement disturbances and brain imaging findings in Asperger's disorder (AD) suggest a dopaminergic deficit in movement regulation. Movement disorders of different etiologies have been quantified and specified with actometry. We compared 10 AD patients with 10 healthy controls, measuring their rest-activities by actometry. The lower limb motor activity was significantly higher in the AD group. They also displayed a rhythmic, periodic movement pattern similar to akathisia. These findings suggest a hypothesis of idiopathic akathisia and a special sensitivity to adverse effects of neuroleptic drugs.     

Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine

To investigate the in vivo role of NMDA receptor stimulation in HIV-1-related CNS neurotoxicity, we evaluated the neuroprotective potential of the NMDA receptor antagonist memantine in transgenic mice which have gp120-induced CNS damage. Brains of mice treated chronically with memantine and of untreated controls were analysed for structural damage by laser scanning confocal microscopy of sections immunolabeled for microtubule-associated protein-2 (MAP-2) and synaptophysin. Qualitative and quantitative analysis of confocal images revealed that memantine treatment substantially decreased neuropathology in gp120 transgenic mice; this included statistically significant improvements in both dendritic and presynaptic terminal density. These results provide in vivo evidence that gp120 can activate neurotoxic pathways that can ultimately result in aberrant NMDA receptor stimulation and neuronal damage in the CNS. They also suggest that clinically tolerated NMDA receptor antagonists may be useful in the prevention of neuronal damage in HIV-1-infected patients.     

Women with irritable bowel syndrome and their perception of a good quality of life.

Irritable bowel syndrome has a negative impact on a person's quality of life, but only a few existing studies have been based on patients' own perceptions. This study therefore aimed to collect information on the view of female patients with irritable bowel syndrome regarding what constitutes a good quality of life for them and to create a healthcare model for these patients. For the study, 30 women with irritable bowel syndrome (median age, 38.5 years; range, 20-65 years) responded in writing to a single, all-inclusive question: "What is your perception of a good quality of life?" When the questionnaires were returned, there was time for a short dialogue, and notes of the conversations were made. Data were analyzed qualitatively according to Burnard's method of thematic content analysis. The answers also were counted and thereby quantified. The women's perception of a good quality of life could be divided into five categories: (a) physical and mental health, (b) social well-being, (c) welfare, (d) strength and energy, and (e) self-fulfillment. According to the results, a healthcare model for patients with irritable bowel syndrome should include four main areas: (a) treatment of the patient's symptoms, (b) confirmation of the patient, (c) confirmation of the diagnosis, and (d) instruction for the patient. The healthcare model should be focused on the primary care level and should include a longitudinal plan of healthcare that also describes the secondary care level.     

Pertussis-Specific Memory B-Cell and Humoral IgG Responses in Adolescents after a Fifth Consecutive Dose of Acellular Pertussis Vaccine

In order to impede the increase in pertussis incidence in the adolescent group, a school-leaving booster dose administered at the age of 14 to 16 years will be introduced in Sweden in 2016. Preceding this introduction, an open-label, randomized, multicenter, clinical trial without a control group and with blinded analysis was performed, investigating both safety and immunogenicity. Reported here are the memory B-cell and serological responses detected in a smaller cohort (n = 34) of the 230 subjects recruited to the study. All subjects had received primary vaccination consisting of three doses of diphtheria–tetanus–5-component pertussis (DTaP5) vaccine, at 3, 5, and 12 months of age, and a tetanus–low-dose diphtheria–5-component pertussis (Tdap5) vaccine booster at 5.5 years. In this study, the subjects were randomly assigned and received either a Tdap1 or Tdap5 booster. Of the 230 participants, 34 subjects had samples available for evaluation of IgG-producing memory B-cell responses. Both vaccine groups had significant increases in pertussis toxin-specific serum IgG levels, but only the 1-component group showed significant increases in pertussis toxin-specific memory B cells. The 5-component group had significant increases in filamentous hemagglutinin- and pertactin-specific memory B-cell and serum IgG levels; these were not seen in the 1-component group, as expected. In conclusion, this study shows that a 5th consecutive dose of an acellular pertussis vaccine induces B-cell responses in vaccinated adolescents. (This study has been registered at EudraCT under registration no. 2008-008195-13 and at ClinicalTrials.gov under registration no. NCT00870350.)     

Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children

Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.