Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease

BACKGROUND: Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis. OBJECTIVES: To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers). METHODS: The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile. RESULTS: Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers (P < .01). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers (P < .05 and P < .01, respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils (r = +0.61; P < .0025) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV(1). CONCLUSION: These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.     

Merkel cell carcinoma with pagetoid spread.

A case of Merkel cell carcinoma showing epidermotropism is presented. The neoplastic cells displayed dotlike immunoreactivity for cytokeratins and strong immunoreactivity for neuron-specific enolase. Although no neuroendocrine granules were found, characteristic paranuclear fibrous bodies were present.     

Primary myeloid sarcoma of the testicle with t(15;17)

The first case of acute promyelocytic leukemia presenting as a solitary testicular mass (myeloid sarcoma) that relapsed in the contralateral testicle is described. The neoplastic cells strongly expressed chloroacetate esterase, myeloperoxidase, CD33, CD43, and weakly, CD117. The presence of many azurophil granules and Auer rods was detected by electron microscopy. Translocation (15;17)(q22;q21.1) was revealed by cytogenetics and was verified by fluorescence in situ hybridization. Contralateral testicle is a favorite site for recurrence in a subset of testicular myeloid sarcomas. Subclassification of all cases of myeloid sarcoma ought to be attempted.     

Gastrointestinal Autonomic Nerve Tumor: A Common Type of Gastrointestinal Stromal Neoplasm

Seven of 15 gastrointestinal stromal tumors from the author's file were classified as plexosarcomas when examined by electron microscopy and immunohistochemistry. Electron microscopy was essential for the diagnosis.     

Impromptu micturitional flow parameters in normal boys

Nonintrusive measurement of the hydrodynamic properties of the urinary stream (uroflowmetry) has been included in many adult urological evaluations as an objective diagnostic tool. Measurement and behavioral problems interfere with practical applications in children. We describe a standard procedure for obtaining "impromptu" micturitional flow parameters in clinical pediatric practice. Statistical correlations of these flow parameters in an unselected group of 142 normal boys between 2 and 12 years old are presented. Useful linear regression equations were derived from the sample to assist the clinician in predicting deviations from normal values. Limitations of the methodology are noted.     

Tubeless Laryngotracheal Surgery in Infants and Children via Jet Ventilation Laryngoscope

We present the first use of tubeless superimposed combined high- and low-frequency jet ventilation (SHFJV) with a jet laryngoscope in laryngotracheal surgery in infants and children. Twenty-eight patients underwent 53 operative procedures. The average age of the patients was 7.3 years. The most common diagnoses were laryngeal papillomatosis and subglottic stenosis. The duration of jet ventilation averaged 33 min. The gas exchange was sufficient in each case. The advantages of SHFJV in the surgery of the laryngotracheal area in infants and children are optimal view at the larynx and trachea, maximum space for the handling, application of the laser without risks, no time limitation, suitability for stenosis, and neither anesthetic nor surgical complications.     

Vitamin D receptor allele combinations influence genetic susceptibility to type 1 diabetes in Germans

Vitamin D has been shown to exert manifold immunomodulatory effects. Because type 1 diabetes is regarded to be immune-mediated and vitamin D prevents the development of diabetes in the NOD mouse, we investigated the role of the vitamin D receptor (VDR) gene as a candidate for type 1 diabetes susceptibility. A total of 152 Caucasian families with at least one affected offspring were genotyped for four VDR restriction-site polymorphisms (FokI, BsmI, ApaI, and TaqI). Whereas the BsmI, ApaI, and TaqI polymorphisms are in strong linkage disequilibrium with each other, no significant linkage disequilibrium with the FokI site was observed. Extended transmission disequilibrium testing (ETDT) was used to detect preferential transmission of allelic combinations to affected offspring. We found significant haplotype-wise ETDT results for the BsmI/ApaI/TaqI (chi2 = 18.886, df = 7, P = 0.0086), the BsmI/TaqI (chi2 = 8.373, df = 3, P = 0.0389), and theApaI/TaqI (chi2 = 17.182, df = 3, P = 0.0006) haplotypes. The "At" and "Bt" alleles confer an increased risk, whereas "AT" and "at" are protective. The combination with the strongest susceptibility was the "BAt" haplotype (64% transmitted, P = 0.0106). Analysis of the FokI site does not provide more information on susceptibility (FokI/BsmI/ApaI/TaqI [chi2 = 24.702, df = 15, P = 0.0541]). These findings suggest a linkage of VDR itself or a nearby gene with type 1 diabetes susceptibility in Germans, confirming respective observations previously made in Indian Asians.     

Combination treatment of IFNalpha2b and ribavirin in patients with chronic hepatitis C and persistently normal ALTs

Combination therapy of interferon-_2b and ribavirin was prospectively evaluated in 20 patients with chronic replicative hepatitis and persistently normal ALTs. Patients with normal ALTs on three or more occasions within 6 months received interferon-_2b 3 MU three times a week with ribavirin 1000–1200 mg everyday for 12 months and had a follow-up of 6 months. HCV genotype 1 was found in 16, and HCV genotype 2 or 3 in 4 patients. No patient experienced an ALT elevation during therapy. Ten of 20 patients (50%) cleared virus at the end of treatment. In an intent-to-treat analysis, a sustained virological response (SR) was achieved in 8 of 20 patients (40%). Nonresponse occurred in 5 patients. Relapse and breakthrough were seen in 2 patients each. Treatment was discontinued in 3 patients due to side effects. Interferon (IFN) ribavirin combination therapy is effective in patients with normal ALTs and appears superior to IFN monotherapy.