Serum Vitamin D Concentration and Markers of Bone Metabolism in Perimenopausal and Postmenopausal Women with Asthma and COPD.

Aging and menopause are closely related to hormonal and metabolic changes. Vitamin D is a crucial factor modulating several metabolic processes. The aim of this study was to evaluate biomarkers of bone metabolism in peri- and postmenopausal women with obstructive lung diseases. Sixty two female patients, 27 with asthma and 35 with COPD, aged over 45 years (median age 58 and 64 years, respectively) were enrolled into the study. The evaluation included lung function, bone mineral density, serum concentration of vitamin D, and bone metabolism markers. The study groups differed significantly in terms of forced expiratory volume in 1 s (FEV1); median values of 1.79 L vs. 1.16 L (p = 0.0001) and 71.2% vs. 53.0% predicted (p = 0.0072) and in vitamin D concentration (12.3 ng/ml vs. 17.6 ng/ml). Total bone mineral density (BMD) was lower in the COPD group (p = 0.0115). Serum vitamin D inversely correlated with the number of pack-years in asthma patients (r = -0.45, p = 0.0192). There was no correlation between serum vitamin D and disease duration or severity, and the Asthma Control Test (ACT) and the modified Medical Research Council (mMRC) dyspnea scores. The serum bone metabolism markers C-terminal cross-linked telopeptide of collagen type I (BCROSS), N-terminal propeptides of procollagen type-1 (tP1NP), and N-mid osteocalcin (OCN) inversely correlated with age in the COPD, but not asthma, patients (r = -0.38, p = 0.0264; r = -0.37, p = 0.0270; and r = -0.42, p = 0.0125, respectively). We conclude that peri- and postmenopausal women with obstructive lung diseases had a decreased serum concentration of vitamin D. Furthermore, vitamin D and body mineral density were appreciably lower in women with COPD than those with asthma.

Metabolic Syndrome as a Factor Affecting Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a systemic disease which may be associated with other comorbidities. The aim of the study was to estimate the incidence of metabolic syndrome (MS) in COPD patients and to assess its impact on systemic inflammation and lung function. MS was diagnosed in accordance with the recommendations of the Polish Forum for the Prevention of Cardiovascular Diseases. The study group consisted of 267 patients with stable COPD in all stages of severity. All patients underwent spirometry with bronchial reversibility testing and 6 min walk test (6MWT). The following blood tests were evaluated: lipid profile, glucose and C-reactive protein as well as serum concentration of IL-6, leptin, adiponectin, and endothelin. MS was diagnosed in 93 patients (35.8%). No differences were observed in the incidence of MS in relation to airflow limitation severity (mild; moderate; severe and very severe: 38.9; 36.3; 35.2 and 25.0%, respectively). FEV1 (% predicted), FVC (% predicted), 6MWT distance (6MWD), age, and the number of pack-years were similar in patients with and without MS. MS was more frequent in males than females (38.7 vs. 28.4%, p > 0.05). Serum concentrations of IL-6, endothelin, leptin, and CRP were higher in the MS group, contrary to adiponectin concentration which was lower (p < 0.01). MS was more frequent in male COPD patients, but there were no differences in its frequency between patients with different severity of airflow limitation. We conclude that MS, as a comorbidity, occurs in all COPD stages and affects systemic inflammation. MS incidence does not depend on COPD severity.

Exacerbations of Chronic Obstructive Pulmonary Disease and Quality of Life of Patients.

Exacerbations of chronic obstructive pulmonary disease (COPD) are one of the most important factors which influence the course of disease and quality of life in COPD patients. The aim of the study was to assess the exacerbation frequency in COPD patients in relation to COPD severity and to evaluate the impact of the number of exacerbations on quality of life. The study included 445 COPD patients in all four progressive stages of the disease according to GOLD classification. The patients recorded exacerbations in diaries. Spirometry, St. George's Respiratory Questionnaire, and dyspnea score were assessed at baseline and after 12 and 24 months from enrollment. After 24 months, 261 diaries were returned. The mean number of exacerbations per year in the sequential GOLD 1-4 stages of COPD was as follows: 1.3 ± 2.1, 1.4 ± 2.0, 1.7 ± 1.8, and 3.4 ± 4.5. A statistical difference in the exacerbation frequency was noted for GOLD 4 and the remaining groups. A significant negative correlation was found between the number of exacerbations and functional status for GOLD 2 and 3 stages. We conclude that the number of exacerbations is the highest in the most severe stage of the disease. The quality of life of patients with moderate and severe COPD correlates negatively with the number of exacerbations.

Influence of denture plaque biofilm on oral mucosal membrane in patients with chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) have the lower airways colonized with pathogenic bacteria in a stable period of the disease and during exacerbations. The etiology of bacterial exacerbations of COPD depends on the underlying disease, the frequency of exacerbations and antibiotic therapy. Microorganisms can be aspirated off the denture plaque biofilm into the lower respiratory tract and could reduce the patient's immunity and cause pneumonia. COPD patients, who are using acrylic dentures in oral cavity, are exposed to denture stomatitis and oral candidiasis. The aim of this study was to establish the composition of denture plaque biofilm and its impact on the oral mucosa in COPD patients. The study included patients in a stable phase of COPD using removable denture and the control group included healthy wearer's appliances. Examinations concerned the oral mucosal membrane and the hygienic condition of prosthetic restorations. Microbiological examinations were performed by taking a direct swab from the surface of acrylic dentures. Seventeen bacterial and fungal strains were isolated from denture plaque of COPD patients, which could be a reservoir of pathogens in the upper and lower airways. The results showed a greater frequency of prosthetic stomatitis complicated by mucosal infections among COPD patients compared to healthy subjects.

The Prevalence of Oral Inflammation Among Denture Wearing Patients with Chronic Obstructive Pulmonary Disease.

Oral inflammation is an important contributor to the etiology of chronic obstructive pulmonary disease, which can impact patient's health status. Previous studies indicate that people with poor oral health are at higher risk for nosocomial pneumonia. Denture wearing is one promoting factor in the development of mucosal infections. Colonization of the denture plaque by Gram-negative bacteria, Candida spp., or other respiratory pathogens, occurring locally, may be aspirated to the lungs. The studies showed that chronic obstructive pulmonary disease (COPD) patients treated with combinations of medicines with corticosteroids more frequently suffer from Candida-associated denture stomatitis. Treatment of oral candidiasis in patients with COPD constitutes a therapeutic problem. Therefore, it is essential to pay attention to the condition of oral mucosal membrane and denture hygiene habits. The guidelines for care and maintenance of dentures for COPD patients are presented in this paper. The majority of patients required improvement of their prosthetic and oral hygiene. Standard oral hygiene procedures in relation to dentures, conducted for prophylaxis of stomatitis complicated by mucosal infection among immunocompromised patients, are essential to maintain healthy oral tissues. The elimination of traumatic denture action in dental office, compliance with oral and denture hygiene, proper use and storage of prosthetic appliances in a dry environment outside the oral cavity can reduce susceptibility to infection. Proper attention to hygiene, including brushing and rinsing the mouth, may also help prevent denture stomatitis in these patients.

Novel FOXG1 mutations associated with the congenital variant of Rett syndrome.

BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder representing one of the most common genetic causes of mental retardation in girls. The classic form is caused by MECP2 mutations. In two patients affected by the congenital variant of Rett we have recently identified mutations in the FOXG1 gene encoding a brain specific transcriptional repressor, essential for early development of the telencephalon. METHODS: 60 MECP2/CDKL5 mutation negative European Rett patients (classic and variants), 43 patients with encephalopathy with early onset seizures, and four atypical Rett patients were analysed for mutations in FOXG1. RESULTS AND CONCLUSIONS: Mutations have been identified in four patients, independently classified as congenital Rett variants from France, Spain and Latvia. Clinical data have been compared with the two previously reported patients with mutations in FOXG1. In all cases hypotonia, irresponsiveness and irritability were present in the neonatal period. At birth, head circumference was normal while a deceleration of growth was recognised soon afterwards, leading to severe microcephaly. Motor development was severely impaired and voluntary hand use was absent. In contrast with classic Rett, patients showed poor eye contact. Typical stereotypic hand movements with hand washing and hand mouthing activities were present continuously. Some patients showed abnormal movements of the tongue and jerky movements of the limbs. Brain magnetic resonance imaging showed corpus callosum hypoplasia in most cases, while epilepsy was a variable sign. Scoliosis was present and severe in the older patients. Neurovegetative symptoms typical of Rett were frequently present.

Smoke inhalation injury in a 2-year-old domestic fire victim.

Smoke inhalation injury is common in victims of domestic fires, among whom children are the most vulnerable. Cyanide poisoning may occur in addition to carbon monoxide poisoning and is challenging to diagnose. In France, the recommended antidotes are hydroxocobalamin for cyanide and hyperbaric oxygen for carbon monoxide. We managed a 26-month-old girl who sustained smoke inhalation injury with both carbon monoxide and cyanide poisoning during a house fire. Despite hydroxocobalamin and sodium thiosulfate therapy combined with hyperbaric oxygen, she had residual neurological impairments 3 months after the injury. The treatment challenges and detailed neurological follow-up data are described.

Iatrogenic mediastinitis in bronchiolitis: Importance of avoiding pharyngeal aspiration.

An 11-month-old infant was hospitalized for his first episode of severe bronchiolitis, with pneumomediastinum on the chest x-ray performed in the emergency room before hospitalization. After a few days, the occurrence of a feverish torticollis motivated a CT scan, revealing mediastinitis. An iatrogenic perforation was objectified in the posterior wall of the esophagus, probably caused by nasopharyngeal aspiration. This exceptional case has never been reported before, except in premature infants. This encouraged us to report this case to change systematic aspiration practices and prefer nasal suctioning in healthy infants with bronchiolitis presenting to the emergency department.

Prognostic value of evoked potentials and sleep recordings in the prolonged comatose state of children. Preliminary data.

OBJECTIVES: Sleep recordings and evoked potentials (EPs) were used in five comatose children to evaluate their predictive value for outcome following a severe comatose state. METHODS AND SUBJECTS: The protocol included EEG, Brainstem Evoked Responses (BERs), Somatosensory Evoked Potentials (SEPs) and polysomnography. From 10 to 15 days post-coma (D10 to D15), EEG and clinical examinations were carried out every second day, then one day in four from 15 to 30 days post-coma (D15 to D30), and one day in seven from D30 to six months (M6). Evoked potentials and Polysomnography were recorded on D10-D15 or D30 in the second month (M2) and in M6. Of the five children, three were in anoxic coma and two in traumatic coma. All had extensive lesions and a Glasgow Coma Scale (GCS) score of less than five. The results of the EEG, polysomnographic and EP recordings were compared to the clinical outcome. RESULTS AND CONCLUSION: In the three anoxic comas we observed BER abnormalities and the absence of SEP N20 associated with wide cortical lesions with brainstem extension. Sleep recordings showed major alterations of the wake-sleep cycle without any improvement in M6. Abnormalities included loss of the normal REM-sleep pattern associated with alteration of NREM sleep and periods of increase in motor activity without EEG arousal. This sleep pattern appeared to be associated with involvement of the brainstem. In the two traumatic comas, alterations of the early cortical SEP responses were less severe and the BERs were normal. Some sleep spindles were observed as well as the persistence of sleep cycles in the first weeks post-coma. The combined use of EEG, EPs and polysomnography improved the outcome prediction in comparison with the use of just one modality. EPs and sleep recordings were far superior to clinical evaluation and to GCS in the appreciation of the functional status of comatose children. The reappearance of sleep patterns is considered to be of favorable prognosis for outcome of the coma state, as is the presence of sleep spindles in post-trauma coma. This study showed that EPs and sleep recordings help to further distinguish between patients with good or bad outcomes.

[A neonatal case of immunoallergic acute interstitial nephritis]. / Néphropathie interstitielle aiguë immunoallergique néonatale : à propos d'un cas.

Acute interstitial nephritis accounts for about 10 % of the cases of acute renal failure. An adverse drug reaction caused by an immunoallergic mechanism is suggested when fever, skin rash, eosinophilia, and eosinophiluria are associated. The outcome is favorable after withdrawal of drug therapy in most cases. We report a case of acute interstitial nephritis induced by immunoallergic drug mechanisms, in a 3-week-old infant who presented with acute renal failure associated with eosinophilia and hepatitis and who had received cefotaxime and gentamicin. The patient's progression was favorable with normalization of renal and liver function 1 week after suspension of antibiotic drugs.

[Enzyme replacement therapy of lysosomal storage diseases]. / Thérapies enzymatiques substitutives des maladies lysosomales.

Extraction and purification of an acid ß-glucosidase from human placenta (alglucerase) for the treatment of Gaucher disease, replaced a few years later by a recombinant enzyme (imiglucérase, Cerezyme(®)), has paved the way to the development of enzyme replacement therapies (ERT) for the treatment of lysosomal storage diseases (LSD) among which Fabry disease for which the long-term efficacy of the two currently available preparations (agalsidase alfa, Replagal(®) and Fabrazyme(®)) is still being investigated. Mucopolysaccharidosis (MPS) type I (Hurler and Scheie diseases), II (Hunter syndrome) and VI (Maroteaux-Lamy disease) also benefit from ERT using laronidase (Aldurazyme(®)), idursulfase (Elaprase(®)) and galsulfase (Naglazyme(®)), respectively. ERT reduces the hepatosplenomegaly and improves the physical and respiratory capacities of MPS patients with a globally acceptable safety profile although the possibility of infusion-associated should always be kept in mind. Alglucosidase alpha (Myozyme(®)) improves the cardiomyopathy and life expectancy of infants suffering from Pompe disease and is under evaluation for the treatment of the juvenile and adult forms of the disease. CNS involvement remains a major challenge for many LSD and innovative research and approaches are needed to address the fact that recombinant enzymes do not cross the blood-brain barrier and therefore are not expected to lead to any improvement in CNS damages, except if alternative routes such as intrathecal administration would be developed. Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.

[The sympathetic nervous system activity estimated on serum concentration of chromogranin A in patients with the chronic heart failure]. / Aktywnosc ukladu adrenergicznego oceniana na podstawie stezenia chromograniny A w zaleznosci od stopnia niewydolnosci krazenia.

BACKGROUND: The sympathetic nervous system is markedly activated in patients with chronic heart disease. This activation can be evaluated by assessing the serum levels of chromogranin A (CgA), the protein which is present in the all neuroendocrine cells. The main human source of CgA are adrenal medullary and sympathetic nerve endings. The aim of the study was to demonstrate if serum concentration of chromogranin A correlated to severity of chronic heart failure and it can be usefulness for clinical diagnosis. MATERIAL AND METHODS: The serum levels of CgA were measured in 123 patients. Patients with chronic heart disease (n = 100) were divided into four groups depending of the severity of heart failure--NYHA classification (B1--NYHA I, B2--NYHA II, B3--NYHA III, B4--NYHA IV). The control group consisted of 23 persons without heart disease. The patients in both groups were examined and had performed tests: electrocardiography, echocardiography, blood morphology and the blood concentrations of creatinine, glucose, electrolytes, lipids. The serum concentration of chromogranin A was assessed by specific and immunoenzymatic sandwich ELISA test. RESULTS: The mean serum concentration of CgA in the control group was 48.43 +/- 2.97 micrograms/L. In the chronic heart disease group the concentrations of CoA increased with the degree of NYHA heart failure and in four groups (B1, B2, B3, B4) the CgA levels were: 42.10 +/- 19.52; 49.84 +/- 22.63; 73.64 +/- 34.08; 106.66 +/- 87.54 micrograms/L respectively. The concentrations in groups B3 and B4 were significantly higher than in control group. The LV ejection fraction was reduced in groups B1-B4 (mean +/- SD): 60.12 +/- 9.20; 47.45 +/- 11.10; 40.28 +/- 9.52%. The CgA concentration was significantly negatively correlated with LV ejection fraction (r = -28). The left atrium was in group B1-B4:--32.94 +/- 4.35, 38.73 +/- 7.87, 42.57 +/- 7.98, 46.32 +/- 10.67 mm. The heart rate rised with the NYHA class (the control group (mean +/- SD): 72.96 +/- 9.15/min) and in the groups B1-B4 (mean +/- SD): 78.15 +/- 14.35, 79.90 +/- 14.67; 85.40 +/- 14.11; 93.74 +/- 16.29/min. The heart rate was significantly higher in B3 and B4 groups. CONCLUSIONS: 1. The serum concentrations of chromogranin A were correlated with the severity of chronic heart failure based on NYHA classification. 2. The CgA concentrations were significantly negatively correlated with the LV ejection fraction. 3. The chromogranin A can be used as a marker of the sympathetic nervous system activation in the patients with chronic heart failure.

[Current opinions about the role of peptide C in the human organism]. / Wspólczesne poglady na temat roli peptydu C w ustroju.

This article present a review on the physiological activity and possible mechanism of action of C-peptide and clinical significance of using this hormone in the treatment of diabetes mellitus. The present results might suggest that, contrary to the prevailing view, C-peptide possesses biological activity and plays an important part in the attenuating or preventing from diabetic complications. It is important to realize that this discovery might someday revolutionize diabetes treatment, however further studies will be required to define and confirm the exact mechanism of C-peptide activity.