Small, Prospective, Observational, Pilot Study in Patients with Severe Asthma after Discontinuation of Omalizumab Treatment.

PURPOSE: Omalizumab has demonstrated clinical efficacy in severe allergic asthma by reducing exacerbation rates and increasing quality of life. However, data concerning its sustained effect after treatment discontinuation are still needed. METHODS: This analysis was an observational pilot study (simple within-subjects design) of 12 patients experiencing severe asthma, treated with omalizumab, for 1 year after treatment discontinuation. We prospectively analyzed clinical measurements (pulmonary functions, inhaled corticosteroid [ICS] doses, Asthma Control Test [ACT] scores, skin prick test [SPT] positivity, fraction of exhaled nitric oxide, and exacerbation rates) and laboratory test results (eosinophils and total immunoglobulin E levels) at the time of discontinuation and 6 and 12 months thereafter. Baseline data (before the treatment period; range, 11-61 months) were collected retrospectively. The treatment effect until discontinuation was calculated. To determine its persistence, repeated measures were compared with baseline levels and analyzed by using a general linear model for repeated measures or the Friedman ANOVA, and χ2 tests in case of normality assumption violation or frequencies. Post hoc analysis was applied by using a simple or repeated contrasts analysis or Wilcoxon signed rank test with Bonferroni correction. FINDINGS: We proved a significant reduction in ICS doses and SPT reactivity and an increase in ACT score during the retrospective treatment phase. Moreover, persistence of these statistically significant effects was recorded 6 months after treatment discontinuation. ACT score and ICS doses (but not SPT reactivity) remained improved for 12 months after discontinuation of omalizumab treatment. IMPLICATIONS: Omalizumab treatment exhibited sustained treatment benefit after its discontinuation for patients experiencing severe allergic asthma.

[Secondary humoral immunodeficiency in patiens with systemic lupus erythematosus]. / Sekundární humorální imunodeficience u nemocných se systémovým lupus erythematodes.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune multisystem disease. The aim of our study was to clarify the frequency of decreased serum immunoglobulin levels in SLE patients. There were evaluated 799 results of serum immunoglobulin levels gained from 157 patients fulfilling revised ACR criteria in the retrospective study. RESULTS: The immunoglobulin levels under the normal range were found in 29/157 (18.5 %) patients. The most frequent was isolated reduction of IgG 12/157 (7.6 %), two persons fulfilled criteria for selective IgA deficiency, and one case possible diagnosis of common variable immunodeficiency (CVID). Additionally we report two cases of SLE patients complicated by severe hypogammaglobulinaemia and infectious complications with necessity of long-term immunoglobulin substitution therapy. The diagnosis of CVID is highly probable in the first case. The second case presents sever drug-induced hypogammaglobulinaemia. This female with lymphoma history and multiorgan impairment due to acute SLE was treated with rituximab after convention therapy failure. CONCLUSION: Humoral immunodeficiency may occur in SLE patients. The monitoring of serum immunoglobulin levels could be a routine in these patients. The CVID diagnosis is possible in patients suffering from recurrent sinopulmonary infections, especially in combination with absence of lupus activity. Rituximab therapy could cause long-term suppression of B lymphocytes with secondary humoral deficiency requiring immunoglobulin substitution therapy.

Cytomegalovirus disease in patients with common variable immunodeficiency: three case reports.

Common variable immunodeficiency (CVID) is the most frequent clinically relevant primary immunodeficiency and shows enormous heterogeneity in clinical presentation. Despite clinical immunodeficiency, opportunistic infections are not a typical manifestation of CVID. A retrospective study of 32 patients followed up for 335 patient-years was performed to determine the frequency of cytomegalovirus (CMV) disease. Symptomatic CMV infection was documented in 3 CVID patients. Patients No. 1 and 2 suffered from CMV pneumonia, with complications due to atypical mycobacteriosis in patient No. 1. Patient No. 3 suffered from CMV enteritis. A history of cancer and chronic hepatitis C infection (patient No. 1), immunosuppressive therapy for interstitial lung disease (patient No. 2) and serious enteropathy complicated with malnutrition (patient No. 3) may have contributed to the complications despite only mild abnormalities in T-cell subpopulations. The direct detection of CMV in bronchoalveolar lavage, stool or tissue samples was the most beneficial diagnostic laboratory method, whereas the detection of CMV DNA in blood did not produce positive results. Adequate treatment of CMV disease led to significant clinical improvement in all 3 patients. The frequency of CMV disease appears to be higher than previously described. In our experience, the probability of opportunistic infections in CVID patients increases with secondary comorbidities and their management.

[Cell death and its role in immunopathogenesis of infectious diseases]. / Bunecna smrt a jeji role v imunopatogenezi infekcnich chorob.

Cell death is still a matter of debate and scientific opinions have been challenged and are not uniform due to complexity of this issue. Recent research has brought some new evidence about the very subtle border between programmed cell death and necrosis. The concept of their mutual independence, broadly accepted for decades, is now significantly challenged. Lack of unified terminology led to the establishment of the Nomenclature Committee on Cell Death (NCCD) which provides recommendations for clear definition of distinct cell death programs. It also appeals for consistent application of this nomenclature in scientific literature. In this work, some keystone knowledge addressing three specific programmed cell death types - apoptosis, autophagic cell death, and pyroptosis which is recognized as a controversial cell death scenario on the border between programmed cell death and necrosis, is reviewed. These cell death scenarios are discussed in the context of pathogenesis of infectious diseases.

The effect of various forms of selenium supplied to pregnant goats on the levels of selenium in the body of their kids at the time of weaning.

The aim of this trial was to compare the effect of long-term supplementation of goats with different forms of selenium on body reserves of selenium in their kids at the time of weaning. Thirty-three pregnant goats were divided into five groups. Group C was control while the other four groups were supplemented with selenium (Se) for 6 weeks before parturition (0.3 mg/goat/day) and after parturition (0.9 mg/goat/day). Group "Se-I" received sodium selenite and three other groups received organic forms: "Se-L," lactate-protein complex; "Se-P," Se-proteinate; and "Se-Y," Se-yeast. The kids were weaned at 3 months of age and samples of tissues (liver, pancreas, myocardium, lungs, kidneys, spleen, thigh, tongue, and diaphragm) were taken after slaughtering. The long-term supplementation of goats with Se influenced Se concentration in all examined tissues of kids. Significant differences (p≤0.01) were found between the control and all experimental groups, except for the renal cortex and pancreas (Se-I). The average increase of Se concentration in overall examined tissues in comparison with the control (100%) was as follows: Se-Y, 192%; Se-P, 167%; Se-L, 161%; Se-I, 144%. The highest efficiency was found in the group supplemented with Se-yeast with a high content of selenomethionine, also the other two organic forms of Se were more efficient than the inorganic form.

[Principles of macrophage resistance to intracellular parasites]. / Principy rezistence makrofagu vuci intracelularnim parazitum.

Intracellular parasitism is a phenomenon present in nature for more than one billion years. Its keystone is the intriguing ability of viruses and some bacteria to survive and multiply inside eukaryotic host cells and to parasitize on their metabolic machinery. According to the classical definition, germs are classified as intracellular parasites only if they are able to survive inside macrophages. However, the ability of germs to survive inside eukaryotic cells is much more common than it was expected earlier. Reaction of macrophages to invading microbes is the key point in the complex immunological resistance of the host. The outcome of the host is substantially linked to macrophage reactivity. For example, if an evading microbe with a replication time of 20 minutes survived inside a host for 24 hours without reaction of innate immunity, there would be more than 2 x 1021 microbes at the end of this period. It would be fatal for the host, indeed. The key activities of macrophages in the sense of protection against intracellular parasites are reviewed. Some mechanisms of microbial defence and some new approaches to clinical diagnosis of the functional status of cells of innate immunity are also discussed.

Schizophrenia in childhood and adolescence.

Schizophrenia is a disorder characterized by delay in neurodevelopment and by a central disorder of recognition (i.e. with generalized cognitive deficit). Connectivity impairments in the areas of the social brain and cerebellum are the "messenger" of abnormal CNS development in schizophrenia. Processes of neuronal reorganization in cortical and subcortical structures, aberrant forms of pruning, sprouting, and myelinization may play a major role in the pathogenesis of a schizophrenic breakdown. Models of neuroplasticity during adolescence can be connected with models of neurodevelopmental vulnerability and models of neurotoxicity to form an integrated approach in order to better understand premorbid adjustment, onset, and course of schizophrenia. The loss of plasticity and aberrant myelinization lead to a deterioration in cognitive functions, social dysfunction and, in individuals with specific genetic vulnerability, to expression of schizophrenia. This article discusses brain development in relation to the diagnosis of schizophrenia and the basic symptoms of childhood schizophrenia (with early and very early onset) and of adolescent schizophrenia.

The contribution of gastric emptying scintigraphy to the treatment of obesity with gastric bandage--preliminary results.

INTRODUCTION: Gastric banding for morbid obesity is among the least mutilating of procedures used in bariatric surgery and is classified as a restrictive surgical method. Although it is widespread, so far, however the mechanism responsible has not been fully explained. METHODS AND RESULTS: The authors present the preliminary results from scintigraphic examination of the evacuation ability of the stomach using food labeled with (99m)Tc-colloid in six obese patients with a gastric bandage. This initial study showed that the functionality of the bandage demonstrated as a significant drop in body weight, is connected with slower evacuation of the stomach. However, the use of adjustable bandages would have significantly slowed and restricted the passage of food through the cardia of the stomach. CONCLUSIONS: Since it can be extremely difficult to adequately objectively determine the functionality of gastric bandages, evaluating the gastric emptying scintigraphy may be useful in fulfilling this purpose.

Benefits of complementary therapy with insulin aspart versus human regular insulin in persons with type 2 diabetes mellitus.

BACKGROUND: Absorption rates of the phosphate-buffered insulin analogs aspart, lispro, and glulisine prevail over that of regular human insulin. The aim of this prospective observational open-label controlled study was to compare the effects of aspart and human regular insulin resulting from their sequential long-lasting routine administration in small preprandial boluses to individuals with type 2 diabetes according to identical algorithms. METHODS: Fifty-seven individuals with type 2 diabetes 64.0 +/- 1.29 (mean +/- SE) years old with diabetes' duration of 12.4 +/- 1.06 years, treated with human regular insulin for 5.2 +/- 0.44 years, and a serum C-peptide level of 1.1 +/- 0.10 nmol/L were enrolled into the study. Following two checkups performed in the course of the 364 +/- 17.9-day baseline period, human regular insulin was replaced with aspart in equivalent boluses, and two checkups in the course of 330 +/- 11.1-day sequential period were performed. The control group consisted of 17 individuals with type 2 diabetes 68.4 +/- 2.36 years old with diabetes' duration of 9.9 +/- 1.57 years, treated with insulin for 4.2 +/- 0.57 years, and a C-peptide level of 1.1 +/- 0.11 nmol/L. Data were analyzed using the statistical program SPSS version 10.1. (SPSS, Inc., Chicago, IL). RESULTS: Following the switch from human regular insulin to aspart, hemoglobin A1c (HbA1c) decreased from 8.4 +/- 0.23% at baseline to 7.9 +/- 0.17% (P = 0.031), and thereafter to 7.5 +/- 0.20% (P < 0.001), while plasma glucose concentrations in 10-point profiles, daily insulin dose (37.1 +/- 1.39 IU/day), body mass index (BMI) (30.5 +/- 0.82 kg/m(2)), and frequency of hypo- and hyperglycemic episodes did not change (P > 0.05). Patients quote satisfaction was good. No adverse events were recorded. In the control group, no significant change of baseline HbA1c (8.4 +/- 0.54%), insulin dose (33.1 +/- 3.17 IU/day), and BMI (32.1 +/- 1.12 kg/m(2)) was found. CONCLUSION: Aspart appears to be more effective than human regular insulin for complementary insulin treatment in individuals with type 2 diabetes.