Induction of the epidermal growth factor receptor and its ligands in nasal epithelium by ozone

BACKGROUND: Ozone is a photochemical oxidant pollutant that is an important public health hazard. Although the inflammatory response that occurs in response to ozone inhalation is well characterized, the mechanisms underlying epithelial cell activation are not well understood. OBJECTIVE: Because the epidermal growth factor receptor (EGFR) is a central regulator of epithelial function, we tested the hypothesis that nasal epithelial cells respond to ozone-induced oxidant stress by modulating expression of the EGFR and its ligands, EGF and transforming growth factor-alpha (TGF-alpha). METHODS: Normal volunteers were exposed to air or 400 parts per billion ozone for 2 hours, and then nasal biopsy specimens were harvested 6 hours later for immunohistochemical analysis of EGFR, EGF, and TGF-alpha. Nasal epithelial cell cultures were exposed in vitro to ozone or TNF-alpha; mediator release was measured by ELISA and cellular EGFR expression by immunoblotting and fluorescence-activated cell sorting analysis. RESULTS: Epithelial expression of the EGFR, EGF, and TGF-alpha were all significantly (P <.05) increased in the nasal biopsy specimens after ozone exposure, and there was a significant positive correlation between EGFR expression and the increase in neutrophil numbers in the nasal epithelium (P =.001, rho = 0.87). In vitro exposure of primary nasal epithelial cell cultures to ozone had no effect on EGFR expression, even though IL-8 release was enhanced. In contrast, exposure to TNF-alpha caused EGFR levels to increase significantly. CONCLUSION: These data suggest that the ozone-induced increase in EGFR expression observed in vivo is indirect, perhaps mediated by neutrophil-derived TNF-alpha.     

Present status of treatment for invasive cervical carcinoma

The results are presented of a retrospective clinical study carried out on 341 patients affected with cancer of the uterine cervix, with lymphography in the pretreatment diagnostic work-up, treated in our Institute from January 1961 to December 1976. The clinical classification of the patients studied was: 157 cases in Stage I (46.0%), 95 cases in Stage II (27.9%), and 89 cases in Stages III and IV (26.1%). During the period considered, the therapeutic approach for carcinoma of the cervix was practically constant and in line with the therapeutic policy most frequently followed for these neoplasms. For the early stages (9/341 patients or 27.6%) preference was given to a radical surgery and postoperative radiotherapy combination; for borderline cases and "bulky" and "barrel-shaped" lesions, radiotherapy usually preceded surgical treatment to enlarge its indications and improve its results (36/341 patients or 10.5%). The cases that were more developed locally or that presented contraindications to surgery received radiological treatment alone (211/341 patients or 61.9%). Radiotherapy treatment consisted of radium therapy performed with a single application of 226Ra conventional sources, followed by percutaneous irradiation with 60Co-teletherapy in the more developed cases and/or in the presence of lymph node metastases. All the patients were submitted to diagnostic lymphography at the onset of the treatment and 92 (26.9%) had lymph node metastases. In the framework of this clinical review, the 5-year disease-free survival from onset of the treatment varied from 88.2% for the cases at Stage Ib occult, 72.5% for the cases at Stage Ib, 63.8% for the Stage II cases, to 40.5% for the cases at Stage III and IV. The presence of a pathologic report at lymphography makes a considerable difference in terms of disease-free, long-term survival after treatment     

Determinants of the severity of comorbid migraine in multiple sclerosis

A high co-morbidity between multiple sclerosis (MS) and migraine has been reported, especially in young female patients affected by a relapsing-remitting (RR) course of MS. In this study, we aimed to elucidate the determinants of the severity of comorbid migraine in MS. Demographic, clinical and psychometric variables were collected from a cohort of 205 RR-MS patients regularly attending to an Italian outpatient MS Centre. Of them, 102 (49.8?%) were diagnosed as affected by comorbid migraine. About one-third of MS patients with comorbid migraine have asked the attending neurologist a specific anti-migraine treatment. Despite this, only few MS patients (10.8?%) reported a prior use of prophylactic drugs, and even fewer (2.9?%) took triptans as pain killers; these proportions were significantly lower when compared with those of a control group of 63 migraineurs subjects without MS (p?<?0.0001 for both comparison). Factors associated with a moderate or severe disability (MIDAS grades III or IV) due to comorbid migraine in MS patients were the depressive state (OR?=?4.294; p?=?0.001), the anxiety trait (OR?=?5.786; p?=?0.004) and an ongoing IFNB treatment (OR?=?2.337; p?=?0.028). Likewise, depression (OR?=?3.453; p?=?0.048) and anxiety (OR?=?4.582; p?=?0.014) were both independent predictors for having a MIDAS grades of III or IV also in migraineurs subjects without MS. Investigating the determinants of migraine severity may allow a better management of MS patients with comorbid migraine. In these patients, a tailored therapeutic approach is warranted to improve their quality of life and reduce the burden of these two chronic and disabling conditions.     

Exit strategies for “needle fatigue” in multiple sclerosis: a propensity score-matched comparison study

Journal of Neurology - Patients with multiple sclerosis on long-term injectable therapies may suffer from the so-called “needle fatigue”, i.e., a waning commitment to continue with the...     

Markers of mechanical asphyxia: immunohistochemical study on autoptic lung tissues

Forensic pathologists are often asked to provide evidence of asphyxia death in the trial and a histological marker of asphyxiation would be of great help. Data from the literature indicate that the reaction of lung tissue cells to asphyxia may be of more interest for forensic purposes than migrating cells. The lungs of 62 medico-legal autopsy cases, 34 acute mechanical asphyxia (AMA), and 28 control cases (CC), were immunostained with anti-P-selectin, anti-E-selectin, anti-SP-A, and anti-HIF1-α antibodies, in order to verify if some of them may be used as markers of asphyxia death. Results show that P- and E-selectins expression in lung vessels, being activated by several types of trigger stimuli not specific to hypoxia, cannot be used as indicator of asphyxia. Intra-alveolar granular deposits of SP-A seem to be related to an intense hypoxic stimulus, and when massively present, they can suggest, together with other elements, a severe hypoxia as the mechanism of death. HIF1-α was expressed in small-, medium-, and large-caliber lung vessels of the vast majority of mechanical asphyxia deaths and CO intoxications, with the number and intensity of positive-stained vessels increasing with the duration of the hypoxia. Although further confirmation studies are required, these preliminary data indicate an interesting potential utility of HIF1-α as a screening test for asphyxia deaths.     

Comparison of upright balance in stroke,Parkinson and multiple sclerosis

Background – Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults. There is a complete lack of studies that assessed quality of life (QoL) trajectory during time in DM1 cohorts. Aim – To analyze changes of QoL in patients with DM1 during a 5‐year follow‐up period and to assess responsiveness of the SF‐36 questionnaire. Patients and Method – At the baseline, this study comprised 84 DM1 patients, of whom 62 were retested after the mean period of 64.2 ± 3.9 months. Severity of muscular weakness was assessed using the Muscular Impairment Rating Scale (MIRS). Patients completed Serbian version of the SF‐36 questionnaire as a measure of health‐related QoL. Results – After 5 years, MIRS score of our DM1 patients showed significant progression of 0.5 grade (P < 0.01). All mental subdomains, role physical, and total SF‐36 scores significantly improved after 5 years (P < 0.01). Unexpectedly, worsening of muscular weakness from mild to severe was in association with improvement of QoL. Conclusion – QoL improved in our cohort of DM1 patients during a 5‐year period despite the progression of the disease. SF‐36 should be used with caution as a patient‐reported outcome measure in DM1 clinical trials.     

The dual task-cost of standing balance affects quality of life in mildly disabled MS people

The aim of this study was to explore the correlations between the dual-task cost (DTC) of standing balance and quality of life (QoL) in mildly disabled patients with multiple sclerosis (MS). In this cross-sectional study, patients affected by MS with an expanded disability status scale (EDSS) score of 3.0 or less and without an overt balance impairment were tested by means of static posturography under eyes-opened (single-task condition) and while performing the Stroop word-color test (dual-task condition), to estimate the DTC of standing balance. The self-reported 54-item MS quality of life questionnaire (MSQoL-54) was also administered to obtain a MS-specific assessment of health-related QoL. Among the 120 screened patients, 75 (53 women, 22 men) were tested. Although there was no impact of the DTC of standing balance on the physical and mental composite scores of MSQoL-54, patients who had a greater DTC of standing balance scored worse on role limitations due to physical problems (p = 0.007) and social function (p < 0.001), irrespective of demographic and other clinical characteristics including walking performance and cognitive status. However, the EDSS step and fatigue also contributed to reduced scores in these two QoL domains (p-values < 0.01). In conclusion, the phenomenon of cognitive-motor interference, investigated as DTC of standing balance, may affect specific QoL domains even in mildly disabled patients with MS and in the absence of an overt balance dysfunction.