Chlamydophila (Chlamydia) pneumoniae induces histidine decarboxylase production in the mouse lung

Chlamydophila (Chlamydia) pneumoniae (C. pneumoniae) is the third most common cause of community-acquired pneumonia and is probably involved in the development of certain chronic inflammatory diseases, including atherosclerosis and adult-onset asthma. Histamine, synthesized by histidine decarboxylase (HDC) from L-histidine, plays an essential role in allergic and inflammatory processes and in cell differentiation. The effect of C. pneumoniae infection on the expression of HDC has not been examined. In the present study, normal Balb/c mice and HDC knockouts, and control mice with a CD1 background were infected intranasally with C. pneumoniae. On days 1, 3, 7, 16 and 31 after infection, the normal Balb/c mice were sacrificed and divided into three groups. In the homogenized lungs of the first group, C. pneumoniae titres were determined and demonstrated peak levels on day 7. HDC production was revealed by a Western blot assay throughout the observation period of 1-16 days, and cytokine concentrations were determined by ELISA. The interleukin-3 (IL-3) and interleukin-6 (IL-6) levels were highest on day 1 and on days 1-3, respectively; the interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels reached the maximum on day 7, but the quantity of IL-4 was still three times higher than that in the control group 16 days after infection. The lungs of the mice in the second group were processed for the in situ demonstration of HDC activity, while the lungs in the third group were stained for C. pneumoniae antigen. The HDC activity was increased predominantly in the bronchial epithelial cells, while C. pneumoniae antigens were expressed especially in the interstitial macrophages. The HDC knockout mice exhibited a higher survival rate after C. pneumoniae infection than did the control mice. These results point to a strong association between local histamine production and other inflammatory mediators and are novel in demonstrating the role of histamine in the pathomechanism of C. pneumoniae infections.     

Progressive divergent shifts in natural and induced T-regulatory cells signify the transition from undifferentiated to definitive connective tissue disease

The objectives of the study is to determine clinical signs and distribution of peripheral T-cell subsets, B cells and T regulatory cells in patients with undifferentiated connective tissue disease (UCTD) and during the development toward well-established connective tissue diseases (CTD). The methods include 46 patients with UCTD were followed and investigated for differentiation into defined CTDs for 2 years. Cell subsets were determined on the basis of cell surface markers, intracellular cytokine production by flow cytometry and serum cytokine levels by ELISA. The results are as follows: 45.6% of UCTD patients developed into a defined CTD. The number and percentage of activated T cells, memory T cells and NKT cells were increased in patients compared with controls. In addition, in patients with UCTD, the percentage of CD4+/IFN gamma+ T(h)1 was significantly higher compared with controls and further increased in patients that developed CTDs. The percentage and absolute number of CD4+CD25+Foxp3+ regulatory T cells (Tregs) were diminished in UCTD patients compared with healthy controls, while the number of CD4+/IL-10+ Tregs increased. The conclusions are Overproduction of IFN gamma and the decrease of natural (Foxp3+) Tregs seem to be characteristic features of UCTD patients. The increased IL-10 production of CD4+ T cells might be a compensatory suppressive mechanism; however, it is probably not able to balance the overproduction of IFN gamma and the observed decrease of Foxp3+ Tregs. The shift toward T(h)1 with increased IFN gamma production in patients with UCTD combined with the degree of immunoregulatory disturbances characterized by the progressive divergent shifts in natural and induced T-regulatory cell populations signify the transition from undifferentiated to definitive CTD.     

First results with wavefront-guided photorefractive keratectomy for hyperopia

PURPOSE: To compare the results of traditional laser photoablation and wavefront-supported customized ablation (WASCA) in hyperopic photorefractive keratectomy (H-PRK). METHODS: This was a prospective study, comparing two treatment groups, each comprising 40 eyes of 20 patients. Wavefront aberrations were examined using a Shack-Hartmann aberrometer. Preoperative refraction was similar in the two groups; in the traditional H-PRK group (Group 1) it was +3.10 +/- 0.85 D, and in the WASCA-guided group (Group 2) it was +2.90 +/- 0.80 D. H-PRK was performed with the Asclepion-Meditec MEL 70 flying-spot excimer laser. The follow-up time was 6 months. RESULTS: In Group 1, mean postoperative refraction was +0.14 +/- 0.24 D, and in Group 2, -0.10 +/- 0.25 D; mean uncorrected visual acuity was 0.92 +/- 0.16 in Group 1 and 0.95 +/- 0.18 in Group 2. Mean best spectacle-corrected visual acuity was 0.96 +/- 0.04 in Group 1 and 1.06 +/- 0.13 in Group 2. In Group 1, 67.5% (27 of 40 eyes), and in Group 2, 85% (34 of 40 eyes) were within +/-0.50 D of target refraction. Regarding change of spectacle-corrected visual acuity in Group 1, 5% (2 of 40 eyes), and in Group 2, 20% (8 of 40 eyes) gained one Snellen line compared to the preoperative; in Group 1, 10% (4 of 40 eyes), and in Group 2, 12.5% (5 of 40 eyes) lost two Snellen lines. In Group 2, the root mean square value for the higher order aberration increased from the initial 0.134 to 0.257 microm at 6 months after surgery. CONCLUSIONS: WASCA-guided hyperopic-PRK treatment was found to be safe and predictable. The results were better than those achieved with traditional PRK performed using the same flying-spot type excimer laser.     

Analysis of antibiotic consumption of five different clinical departments,especially considering the features of hematology departments

The importance of antibiotic consumption and bacterial resistance analysis is unquestionable. Although the WHO has been recommending the use of ATC/DDD method for the analysis of drug utilization for about 20 years, only limited numbers of publications are available considering the antibiotic consumption of in-patients. In the present study--with the help of the mentioned method--we analysed the utilization of antibiotics in 5 clinical departments. We also investigated the connection between antibiotic consumption, bacterial resistance and enterococcal sepsis at the haematologic department. We could follow the successful impact of the implementation of the new guideline.     

Dalteparin sodium treatment during resuscitation inhibits hemorrhagic shock-induced leukocyte rolling and adhesion in the mesenteric microcirculation

BACKGROUND: Ischemia/reperfusion-induced polymorphonuclear neutrophil leukocyte (PMN) adhesion and extravasation are pivotal for the development of postinjury multiple organ failure. We hypothesized that the deleterious microcirculatory consequences of hemorrhagic shock (HS) could be altered by low-molecular-weight heparin (LMWH) therapy. Our aim was to investigate the effects of dalteparin sodium on leukocyte-endothelial cell interactions when LMWH treatment was initiated before HS or during resuscitation. METHODS: Anesthetized dogs underwent HS (40 mm Hg mean arterial pressure for 60 minutes) and resuscitation either with shed blood or with lactated Ringer's (LR) solution. LMWH or conventional heparin sodium pretreatment was administered subcutaneously before hemorrhage; or LMWH was given intravenously during resuscitation. Mesenteric postcapillary venules were observed by intravital video microscopy before and after HS, and 60 minutes, 120 minutes, and 180 minutes after resuscitation, and leukocyte rolling and firm adherence were determined. RESULTS: HS significantly increased PMN rolling and adhesion in the mesenteric microcirculation. LMWH, but not heparin sodium pretreatment, significantly inhibited both primary and secondary interactions. LMWH treatment was also effective when initiated during resuscitation. LMWH exerted the same inhibitory effect regardless of the type of resuscitation. CONCLUSION: LMWH treatment during resuscitation effectively inhibits PMN rolling and adhesion.     

Results of mammographic screening at the Mammary Center of Debrecen in 1999 and 2000

INTRODUCTION: The screening mammography decreases the mortality of female breast cancer. METHODS: A complex, independent centre of screening mammography has been operating in Debrecen since 1999. RESULTS: The number of the examinations were 10,399 in 1999 and 13,800 in 2000. The number of explored breast cancer cases were 43 (0.41%) in 1999 and 62 (0.45%) in 2000. CONCLUSION: Although the mortality reduction can be exactly measured after several years, we are convinced that the chances for a better life of these 107 women operated on with breast cancer in early state increased thanks to our project. The results of the breast cancer screening program in Debrecen fulfilled the professional requirements of mammographic service-screening.     

Epidermal growth factor receptor (EGFR): therapeutic target in the treatment of lung adenocarcinoma

Revolution in biotechnology made possible to identify those gene errors, which via their encoded proteins (mostly kinase enzymes) are key players in tumor development, growth and progression, and could be considered as molecular targets in tumor diagnosis and therapy. Activity of EGFR (epidermal growth factor receptor), an outstanding representative of the regulatory cell surface receptors, can be inhibited by drugs proved for clinical use. In the past year many groups observed that those lung adenocarcinoma cells, which contain activating mutation in the tyrosine kinase domain of EGFR show remarkable sensitivity to anti-EGFR compounds. The basis of the effective therapy is the identification of the mutations. The clinical advantage of EGFR is an example from the coming age of tumor chemotherapy, when the presence of molecular targets will guide the therapeutic choice.     

Clinical symptoms, diagnosis and treatment of multiple endocrine neoplasia type 1. Results of genetic screening in Hungarian patients

Multiple endocrine neoplasia type 1 syndrome is an autosomal dominant disorder characterized by endocrinopathies involving the parathyroid glands, anterior pituitary gland, and pancreas. Also, it may be associated with foregut carcinoid, adrenocortical tumors and non-endocrine tumors. After reviewing the prevalence, genetic background, clinical symptoms, diagnosis and treatment of the disorder, the authors present their genetic screening method used for the detection of mutations of the MEN1 gene (prescreening of polymerase chain reaction amplified exons using temporal temperature gradient gel electrophoresis followed by direct DNA sequencing). Using this method, the authors identified disease-causing MEN1 gene mutations in 9 probands (small deletions in 2 cases, insertion in 2 cases, nonsense mutations in 2 cases and missense mutations in 3 cases). Of the 9 mutations, 4 proved to be novel mutation not reported in the literature. Family screening indicated de novo mutations in 2 probands. In addition to mutations, several sequence polymorphisms were also detected. The authors conclude that one of the major advantages of genetic screening in families with MEN1 syndrome was the identification of family members carrying the mutation who should be regularly screened for disease manifestations and those not carrying the mutation in whom clinical screening is unnecessary. Also, genetic screening may be useful in cases when MEN1 syndrome is suspected, but the clinical manifestations do not fully establish the diagnosis of MEN1 syndrome.