Circulating P-Selectin and Its Glycoprotein Ligand in Nondiabetic Obstructive Sleep Apnea Patients.

Selectins and their ligands play an important role in atherosclerosis. The role of these adhesion molecules in the pathogenesis of obstructive sleep apnea (OSA) may be of clinical relevance. Therefore, the aim of this study was to assess the serum content of platelet P-selectin (P-SEL) and P-selectin glycoprotein ligand 1 (PSGL-1) in different OSA stages. The study was performed in nondiabetic patients, aged 32-71, in whom OSA was verified by polysomnography. The apnea/hypopnea index (AHI) was used to stratify OSA stages: AHI <5, no sleep pathology (OSA-0); AHI 5-15, (OSA-1); AHI 16-30, (OSA-2); and AHI >30, (OSA-3). There were 16 patients in each group. P-SEL and PSGL-1 were assessed by ELISA kits. There were no appreciable differences in the patients' glucose or high-specificity C-reactive protein content. We found that P-SEL and PSGL-1 significantly increased from OSA-0 to OSA-3. There were the following positive associations in all OSA patients: P-SEL vs. AHI, PSGL-1 vs. AHI, and P-SEL vs. PSGL-1. In addition, the adhesion molecules are associated with the anthropometric parameters, oxygen saturation, and sleep architecture in the OSA-1 group. We conclude that the adhesion molecules consistently increase in the blood of nondiabetic OSA patients, along with progression of disorder severity.

Oxidative Stress Markers and Severity of Obstructive Sleep Apnea.

Oxidative stress underlies both obstructive sleep apnea (OSA) and atherosclerosis. The aim of the study was to assess the markers of oxidative stress in plasma at different stages of OSA in non-smoking obese Caucasian males aged 41-60, with normal oral glucose tolerance test. All patients were subjected to clinical and polysomnographic examinations. The stage of OSA severity was set according to the following criteria of the apnea-hypopnea index (AHI): AHI < 5/h - no disease (OSA-0; n = 26), AHI 5-15/h - mild disease (OSA-1; n = 26), AHI 16-30/h - moderate disease (OSA-2: n = 27), and AHI > 30/h obstructive episodes per hour - severe disease (OSA-3; n = 27). Plasma total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS), reflecting the level of lipid peroxides, were determined spectrophotometrically. We found that TAS decreased and TBARS increased significantly from OSA-0 to OSA-3. We conclude that the oxidative stress markers are conducive to setting the severity of OSA in normoglycemic patients.

Paraoxonase 1 Gene L55M Polymorphism and Paraoxonase 1 Activity in Obstructive Sleep Apnea Patients.

The antioxidant enzyme paraoxonase-1 (PON1) may limit oxidative stress in the development of cardiovascular diseases (CVD) and obstructive sleep apnea (OSA). The aim of the study was to determine PON1 gene L55M polymorphism in OSA-positive and OSA-negative subjects, along with paraoxonase activity of the enzyme (PON1-act). Caucasians aged 25-75, with BMI 19.0-53.0 kg/m2 and no acute or severe chronic disorder underwent polysomnography, and OSA-negative (n = 44) and OSA-positive (n = 57) groups were established. The following parameters were assessed: arterial blood pressure and serum glucose, lipids, C-reactive protein, and homocysteine. Genomic DNA was extracted and amplified, and automatic sequencing was used to confirm the LL, LM, MM genotypes. PON1-act was measured spectrophotometrically using paraoxon as a substrate. We found that frequency of polymorphisms differed significantly between the OSA-negative and OSA-positive patients (p < 0.05). Increased PON1-act was observed in the LL-genotype versus the LM + MM-genotype in the study population (p < 0.05). PON1-act was higher in the OSA-negative compared with OSA-positive patients (p < 0.001); in general and in the subgroups presenting the LL or LM genotype. In addition, there was an inverse relationship between PON1-act and LDL-cholesterol in the entire study population. The OSA-positive group presented an inverse relationship between PON1-act and fasting glucose. We conclude that patients could benefit from the LL genotype related with higher activity of PON1. OSA pathology might decrease the enzyme activity, despite the presence of L allele.

Carotid artery intima-media thickness in hypertensive patients with obstructive sleep apnea.

In this study we determined the relationship between the severity of obstructive sleep apnea (OSA) and body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), and carotid intima-media thickness (cIMT) in 30 hypertensive male patients, aged 30-70, with newly diagnosed OSA (15 with moderate OSA - Group A, and 15 with severe OSA - Group B) and 20 non-OSA hypertensive individuals (Group C). We revealed significant differences in cIMT between Groups B and C (0.9 ± 0.3 vs. 0.6 ± 0.1 mm and 1.0 ± 0.4 vs. 0.6 ± 0.2 mm in the right and left common carotid arteries, respectively; p <0.05). Increased carotid intima-media thickness in severe OSA was accompanied by higher systolic and diastolic blood pressures compared with both moderate OSA and control subjects. We conclude that in severe OSA increased blood pressure goes in tandem with the thickness of carotid intima-media, which helps explain increased cardiovascular risk in these patients.

Impulse oscillometry in the diagnosis of airway resistance in chronic obstructive pulmonary disease.

Spirometry is a standard lung function test for diagnosis and staging of chronic obstructive pulmonary disease (COPD). Impulse oscillometry (IOS) can be complementary to spirometry, especially in patients at advanced age and with physical or mental disorders who cannot be diagnosed through spirometry. The aim of this study was to compare IOS and spirometry in the assessment of airway obstruction in COPD. The study was conducted in 112 stable COPD patients, including 29 females and 83 males of the mean age of 69±11 years. The oscillometric evaluation included total (R5), peripheral (R5-R20), and negative reactance (X5), which were compared with the predicted forced expiratory volume in 1 s (FEV1%pred). The findings show a significantly negative correlation between FEV1%pred and the R5, R5-R20, and X5. COPD patients had increased R5, R5-R20, and X5. The severity of bronchial obstruction found by impulse oscillometry correlated well the spirometric assessment. IOS is a simple to perform test that may be helpful for functional examination of COPD patients.

Phenylketonuria is not a risk factor for gut mucosa inflammation: a preliminary observation.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of amino acid metabolism in which high phenylalanine (Phe) concentrations in the central nervous system adversely affect its development and functioning. In PKU high oxidative stress and inefficiency of free radical scavenging may lead to systemic chronic inflammation. We hypothesised that in PKU gut mucosa is chronically inflamed and that this leads to release of calprotectin from neutrophils and monocytes. AIM: The aim of this study was to compare intestinal mucosa inflammation status, as measured using fecal calprotectin, in patients with PKU irrespective of compliance, and healthy controls. PATIENTS AND METHODS: Forty-four patients with classical PKU were included in the study (21 male, 23 female; aged 0-41 years; mean ± SEM: 16.5 ± 1.7 years). Forty-eight healthy subjects (HS) aged 9-68 years (29.4 ± 2.6 years) comprised the control group, of whom 21 were male and 27 female. Among PKU patients 25 had normal Phe blood concentrations and in 19 they were elevated. In all subjects calprotectin stool concentrations were assessed (PhiCal ELISA, Calpro, Lysaker, Norway). RESULTS: Normal FC (fecal calprotectin) concentrations were found in 43 (97.7%) PKU patients and 46 (95.8%) HS. No correlation between dietary control of Phe blood concentrations and FC levels in PKU patients was found. CONCLUSIONS: No detectable intestinal inflammation occurs in phenylketonuria. Lack of dietary control and elevated Phe levels do not seem to be risk factors for inflammation of the mucosa of the gut.

The evaluation of selected serum mineral concentrations and their association with insulin resistance in obese adolescents.

BACKGROUND: In obesity, elevated insulin resistance is observed, which may be associated with disturbances in mineral status in the body. The few studies concerning the status of minerals and their relationships with insulin resistance and body composition in adolescent populations have brought inconclusive results. AIM: of this study is, thus, to assess serum mineral concentration in obese adolescents, and to evaluate their potential association with insulin resistance. SUBJECTS AND METHODS: Seventy-eight obese adolescents and 20 healthy volunteers aged 12-18 years were recruited for the study. Selected anthropometrical measurements and levels of iron, zinc, copper, calcium, and magnesium were assessed in serum. Insulin resistance in the participants was evaluated according to the homeostatic model of assessment for insulin resistance (HOMA-IR) protocol. Levels of iron, zinc, copper, calcium, and magnesium were assessed in serum. RESULTS: Obese subjects had significantly higher HOMA-IR indices than the control group. Compared to healthy subjects, the serum concentration of zinc, calcium, and magnesium was significantly lower in obese subjects. A significant inverse relation was found between HOMA-IR and zinc levels in serum. CONCLUSIONS: Obese adolescents have a poorer mineral status (especially zinc) than adolescents of normal weight, which can contribute to insulin resistance.

Plasma selectins in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is an independent risk factor in the pathogenesis of -cardiovascular diseases. The aim of the study was to analyze three specific adhesion molecules involved in the development of an atherosclerotic plaque: E-selectin (endothelium), L-selectin (leukocyte surface), and P-selectin (from platelet), circulating in plasma in patients at different OSA severity. Eighty non-smoking male Caucasians aged 30-64 were enrolled into the study after clinical, biochemical, and polysomnographic examinations. The patients were divided into four groups based on the results of apnea/hypopnea index (AHI): OSA-0 with AHI 0-4.9 (n = 20), OSA-1 with AHI 5-15 (n = 21), OSA-2 with AHI 16-30 (n = 18), OSA-3 with AHI ≥ 31 (n = 21). Complete blood count, oral glucose tolerance test, fasting lipid profile, C-reactive protein and insulin, and plasma concentrations of soluble E-selectin, P-selectin and L-selectin were measured. We found a progressive increase in the concentrations of all three selectins with the severity of OSA. In conclusion, the level of plasma adhesion molecules may be indicative of OSA severity and may contribute to cardiovascular sequelae.

Lung impairment in scleroderma.

Scleroderma typically manifests as fibrosis of the skin, but may also involve other organs, particularly the lungs. Interstitial lung disease and functional abnormalities are observed in the majority of patients. The aim of this study was to evaluate radiological changes in the lungs and their correlation with functional disorders in scleroderma patients. The study was conducted in 37 scleroderma patients (F/M-31/6). High resolution computed tomography (HRCT), Warrick score system and spirometry, body plethysmography, and lung diffusion examinations (DLco) were performed. The HRCT showed septal and subpleural lines in 70%, ground-glass opacities in 51%, and honeycomb lungs in 30% of the cases. The DLco values were decreased in 92% of the patients. Total lung capacity (TLC) showed a restrictive pattern in 24% of the patients, and only in 11% of them obstruction predominated. The Warrick score correlated inversely with both DLco (r=0.36; p>0.05). Interstitial lung disease often coexists with scleroderma and is accompanied by functional lung abnormalities.

Endothelium-derived markers and antioxidant status in the blood of obstructive sleep apnea males.

OBJECTIVE: The relationship between obstructive sleep apnea (OSA) and cardiovascular disease is intensively discussed. Endothelial leukocyte adhesion molecule (E-selectin) is one of factors facilitating leukocyte migration to the subendothelial layer which could be considered proatherogenic. The aim of the study was to determine E-selectin levels and total plasma antioxidant status (TAS) in the blood of different stage OSA patients. METHODS: Non-smoking, OSA-suspected males, aged 30-63, were selected for the study. An EMBLA polysomnographic system was used to establish the severity of apneic episodes. The results of apnea/hypopnea index (AHI) allowed dividing patients into the following groups: OSA-0 with AHI 0-4.9 (n=14), OSA-1 with AHI 5-15 (n=14), OSA-2 with AHI 16-30 (n=13), OSA-3 with AHI > or =30 (n=13). Complete blood count (CBC), glycemia during oral glucose tolerance test, fasting plasma lipid profile, uric acid, and high sensitivity C-reactive protein (hsCRP) were estimated among routine parameters. We determined plasma concentrations of E-selectin and total antioxidant status. RESULTS: We found progressively decreasing concentrations of TAS (P=0.03) and increased concentrations of E-selectin (P=0.0001) from OSA-0 to OSA-3 subjects. No correlation between E-selectin and metabolic parameters was noted. - CONCLUSION: In the studied OSA groups, E-selectin appeared an independent proatherogenic factor.

Onconeuronal and antineuronal antibodies in patients with neoplastic and non-neoplastic pulmonary pathologies and suspected for paraneoplastic neurological syndrome.

OBJECTIVE: Onconeuronal antibodies are important diagnostic tool in patients with suspicion of paraneoplastic neurological syndromes (PNS). However, their role in PNS pathophysiology and specificity for particular neurological manifestation remains unclear. The aim of this study was to evaluate onconeuronal and antineuronal antibodies in patients with pulmonary pathologies and suspected for PNS. MATERIAL AND METHODS: Twenty one patients with pulmonary pathologies were selected from the database of 525 consecutive patients with suspicion of PNS. Patients' sera were screened for the presence of onconeuronal and antineuronal antibodies by means of indirect immunofluorescence; the presence was confirmed by Western blotting. Clinical data were obtained from medical records, hospital data base, and questionnaire-based direct telephone contact with patients. RESULTS: Among 21 patients, aged 54 +/-11, with pulmonary pathologies, the most frequent neurological manifestations were neuropathies. Typical PNS included paraneoplastic cerebellar degeneration (PCD) and limbic encephalitis (LE). We found cases with multiple onconeuronal antibodies (anti-Ri and anti-Yo) and coexisting PNS (PCD/LE). Well-defined onconeuronal antibodies were identified in 23.8% of patients. Among antineuronal antibodies, the most frequent were anti-MAG (23.8%). ROC curves analysis revealed high sensitivity of onconeuronal and antineuronal antibodies for typical PNS and lower for pulmonary malignancies. CONCLUSIONS: Tests for antibodies are highly sensitive for the diagnosis of typical paraneoplastic neurological syndromes. Anti-myelin and anti-MAG antibodies are associated with non-neoplastic pulmonary diseases. Patients with well-defined onconeuronal antibodies require careful screening and follow-up, because the PNS diagnosis indicates a high probability of an underlying malignancy.

Adipocytokines in sleep apnea syndrome.

OBJECTIVE: Biomarkers of adipose tissue may affect glucose and lipid metabolism and present pro-inflammatory properties, thus could be involved in the pathobiochemistry of cardiovascular disease (CVD). The coexistence of sleep apnea syndrome (OSA) and metabolic risk factors of CVD is worth explaining. The aim of the study was to compare the serum adipocytokines in subjects with and without OSA, who had all elevated body mass index (BMI). METHODS: Overweight (BMI: 25.0-29.9 kg/m2) and obese (BMI: 30.0-39.9 kg/m2) OSA-suspected Caucasian males, aged 30-63, with no acute disease or chronic disorder underwent polysomnographic evaluation to select OSA-positive (AHI > or = 5) and OSA-negative (AHI <5) subjects. Four subgroups were created of 18 persons each: Over(weight)-OSA-Neg, Over-OSA-Pos, Obese-OSA-Neg, Obese-OSA-Pos. In all subjects, plasma carbohydrate and lipid metabolism parameters, and serum uric acid, resistin and leptin concentrations were determined. RESULTS: A decreased resistin level was observed in Over-OSA-Pos vs. Over-OSA-Neg subjects (P=0.037) as well as in Obese-OSA-Pos vs. Obese-OSA-Neg (P=0.045). No differences in leptin concentrations were observed. A positive correlation between leptin and BMI was in both overweight subgroups and a negative one between resistin and fasting glucose was in both obese subgroups. CONCLUSIONS: OSA may decrease the serum resistin level in subjects with excess body mass and also may contribute to glucose metabolism, but has no influence on the leptin level.

Analysis of serum copper and zinc concentrations in cancer patients.

Several studies have shown that plasma copper concentrations are increased in various carcinomas. Zinc acts as a cellular growth protector, including growth of neoplastic cells, and its deficiency was demonstrated to be involved in several stages of malignant transformation. However, the usefulness of the serum zinc and copper determinations in cancer prevention, detection, monitoring treatment, and prognosis requires further investigations. The aim of the present study was to compare the serum copper and zinc levels in patients with cancer of the lung (PC), breast (BC), gastrointestinal tract (GIC), and gynecological (GYNC) malignancy with progress of the disease. The results of the study have shown a significant increase in the mean total serum Cu levels and the serum Cu/Zn ratio in all patient groups with cancer compared to a control group. Increased mean serum concentrations and Cu/Zn ratios were found in the whole group (ALLC), and for the GIC and GYNC groups with local as well as metastasized (Meta) disease in comparison with the control group. The mean serum concentrations of Zn were decreased only in metastasized ALLC and GYNC groups.

[Acetylation phenotype in patients with lung cancer]. / Fenotyp acetylacji u chorych na raka pluca.

The acetylation phenotype is genetically predetermined. It might influence the development of several diseases. It can also be changed by the active process of diseases. The aim of the study was to determinate the acetylation phenotype of individuals with lung cancer. Sulfadimidine acetylation study was undertaken in 30 patients with lung cancer and 30 individuals of control group. There is a significantly higher proportion of slow acetylators in the group of patients with lung cancer than in those without the disease.

[Evaluation of the character of morphologic traits in persons with obstructive sleep apnea]. / Ocena charakteru cech morfologicznych osób z zespolem obturacyjnego bezdechu sennego.

The aim of the study was carried out to show the anthropometric analysis of patients with obstructive sleep apnoea syndrome and to answer the question about the relations between the degree of SAS and obesity. The research has begun since May 1993 in an interdisciplinary team. The study was carried out in a group of 40 men diagnosed as SAS in Sleep Apnoea Unit of Department of Pulmonary Diseases. The anthropometric analysis consists of basic somatometric measurements. The relations between obesity and the degree of apnoeas was determined by analysis of variance and the model of single and multiple regression. The obtained results demonstrate the dependence between the grade of apnoeas pathology during sleep and the measurements of upper body parts. The slope of the line B not equal to 0 indicates that the intensity of SAS increases in patients "commonly considered as obese". Obesity is an important factor leading to disturbances in respiratory ventilation. An important development of fatty tissue of the neck can cause pressure changes and can induce adipose degeneration. An increased fatty thickness of the thorax is a factor which can lead to the aggravation of symptoms.

Hospital staff and smoking habits: do we need modification of smoking behavior in Polish hospitals?

The purpose of the work was to analyze the smoking behaviors of the medical staff in hospitals. A typical group of employees in one of the biggest hospitals in Poland was examined thoroughly. The medical examination was carried out by means of standardized investigative instruments--questionnaires processed by the European Network for Smoke-free Hospital. In the studied group, 26% of persons admitted that they smoked, while nearly 12% persons confirmed their addiction. Statistically, it was confirmed that addiction to smoking is conditioned by practice, but the percentage of smoking people was the lowest in the professional group of physicians. However, physicians admitted they smoked in hospitals most often. It is a crucial factor for the psychological preventive treatment as well as for changes in the health behaviors among patients. Also, some factors, which determined smoking, such as a large number of duty hours, were identified. On the basis of the analysis of health behaviors, the authors made an evaluation of the possible solutions that could lead to a reduction of the percentage of smoking employees in the health public institutions.

Relationship between nutritional status and pulmonary function in adult cystic fibrosis patients.

Cystic fibrosis (CF) is a multisystem autosomal recessive disorder caused by the mutation of a single gene that encodes for the CF transmembrane regulator protein. Clinically, CF is characterized by chronic pulmonary infection, pancreatic insufficiency, and excessive losses of sweat electrolytes. Along with lung function, nutritional status appears one of the most important prognostic indicators in CF patients. In this study we examined the relationship between nutritional status and pulmonary function in adult CF patients. A group of 39 CF patients (mean age 23.9 +/-3.7 years) was studied. The mean value of body mass index (BMI) was 19.5 +/-2.9kg/m(2) (12.8-24.9kg/m(2)). The patients were grouped according to the presence or absence of malnutrition. Malnutrition was established in 11 patients (28.2%), 5 patients suffered from severe malnutrition. 28 patients (71.8%) had a normal nutritional status, but according to ESPEN guidelines, 9 of those patients were at risk of malnutrition. Statistical analysis revealed a significant difference between malnourished and not malnourished patients with respect to FEV(1)% and FVC%. Moreover, the patients with malnutrition were significantly more frequently colonized by P. aeruginosa and fungi and less so by MSSA.

Biological status of adult patients with cystic fibrosis.

Cystic fibrosis (CF) is the most common autosomal disorder in the Caucasian population. The main goal of the study was to assess the biological condition of adult patients with CS. Data of 90 CF patients aged 18-31 were considered. The biological condition was determined by the measurement of somatometric traits and the nutritional status. The results show a considerable physical retardation and a poor nutritional status of the studied patients. Nearly 45% of the patients showed symptoms of malnutrition, ranging from slight undernutrition to emaciation. The results, however, show a considerable variability of data among the CF patients compared with the healthy population. A significant relationship between the type of mutation and nutritional status was demonstrated.

Oxidative stress markers in the blood of persons with different stages of obstructive sleep apnea syndrome.

The aim of the study was to determine some biochemical factors reflecting oxidant-antioxidant balance in the blood of patients being in different stages of the obstructive sleep apnea syndrome (OSAS). The patients, suspected of OSAS, were submitted to biochemical and somnographic examinations. APolyMesam device was used to establish the severity of apnea episodes. The control group was composed of subjects without OSAS. The following parameters were determined: concentration of plasma total antioxidant status, TAS; activity of erythrocyte Cu, Zn-superoxide dysmutase, SOD; plasma lipid peroxidation products, TBARS. The OSAS patients had lower levels of SOD and TAS, and increased level of TBARS. We conclude that oxidative stress markers increase in the blood of OSAS patients to a variable degree, depending on the severity of the syndrome and, therefore, may be suitable for a clinical follow-up of such patients.

Correlation between the stage of cystic fibrosis and the level of morphological changes in adult patients.

The aim of this study was to evaluate the correlation between the stage of cystic fibrosis and the intensity of accompanying morphological changes--including transmission electron microscopy--within bronchial mucosa. The stage of the disease was assessed on the basis of clinical status and radiological and endoscopic examination. We focused on morphological changes in epithelial cells, the presence of metaplasia and/or dysplasia, the type of inflammatory infiltrate, and the presence of epithelial ulcerations, thickening of epithelial basement membrane and collagenization of lamina propria. We found two clinically different patients groups. The first one was in a poor clinical condition, advanced inflammatory fiberoptic bronchoscopy and radiological changes, multiple exacerbations, and with chronic inflammation and only focal appearance of ciliated epithelium. Moreover, squamous cell metaplasia and dysplasia was diagnosed in 3 and 4 cases, respectively. The other group, in a better clinical condition, had normal BMI and small changes on chest Xray. In this group the diagnosis of cystic fibrosis was made at later age. Two patients from this group displayed features of acute phase; ciliated epithelium was covering the whole sample. After statistical analysis, we found a correlation between the clinical course and the morphological changes in bronchial mucosa. Bronchial ulcerations, squamous cell metaplasia and dysplasia were found in the group with the more severe clinical course.