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Biomedical subjects

J Zieliński

Publications and source records attributed to J Zieliński.

At least 19 recordsLinked to original sources

Differences in responses upon corticosteroid therapy between smoking and non-smoking patients with COPD.

Inhaled corticosteroids have a high level of topical anti-inflammatory activity. However, in patients with COPD these drugs have been reported to exert limited effects. A reduction in histone deacetylase (HDAC) activity is suggested to prevent the anti-inflammatory action of corticosteroids. Cigarette smoke is known to reduce HDAC expression. The aim of this study is to compare the outcome of corticosteroid therapy in both smoking and non-smoking COPD patients. Twenty-three smoking patients and 18 ex-smoking patients with COPD were treated with inhaled corticosteroids for a period of 2 months. Blood and induced sputum samples were collected before and after treatment. Values of FEV(1) %-predicted did not change upon the therapy, but there was a trend to improve in the ex-smokers (63.1 -> 64.8%-pred.), compared with a decrease in the smokers (63.3 -> 61.6%-pred.). The levels of the pro-inflammatory cytokine IL-8 increased in the group of smokers from 379 +/-78 to 526 +/-118 ng/ml. Although not significant, a slight decrease from 382 +/-70 to 342 +/-62 ng/ml was observed in the group of ex-smokers. The neutrophil related elastase activity showed similar effects after steroid treatment, it went up from 36.4 +/-12.0 to 113.5 +/-9.7 nmol/l in smokers, and decreased from 346.2 +/-72.1 to 131.1 +/-6.5 nmol/l in ex-smokers with COPD. These results support the evidence that inhaled corticosteroids have no anti-inflammatory effects in COPD patients, but only when these patients are still smoking. Smoking cessation seems the best therapy for COPD patients.

Adrenal Cortex Hormones↗

Influence of N-acetylcysteine on ICAM-1 expression and IL-8 release from endothelial and epithelial cells.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. The initial step in the inflammatory process is overexpression of adhesion molecules, which leads to excessive transmigration of neutrophils. One of these adhesion molecules is ICAM-1 which is elevated in COPD patients. In this study we evaluated the influence of N-acetylcysteine (NAC) (0.01 mM-30 mM) on the cytokine-induced (TNF-alpha/IL-1 beta) expression of the ICAM-1 adhesion molecule and on IL-8 release in endothelial (ECV-304) and bronchial epithelial (H292) cell lines. The methodology used consisted of immunochemistry for the assessment of surface ICAM-1 and ELISA method for that of soluble ICAM-1 and IL-8. NAC inhibited the TNF-alpha/IL-1 beta-stimulated ICAM-1 expression and IL-8 release from both cell lines in a concentration dependent manner. The most effective concentrations were 30 mM and 20 mM (99 and 90% inhibition respectively, P<0.01). We conclude that NAC is an effective inhibitor of TNF-alpha/IL-1 beta- stimulated ICAM-1 and IL-8 release in endothelial and epithelial cells. This fact highlights the anti-inflammatory potential of NAC in COPD.

Acetylcysteine↗

Effects of intermittent hypoxia on pulmonary haemodynamics: animal models versus studies in humans.

The aim of this review was to analyse the effects of intermittent hypoxia (IH) on pulmonary haemodynamics, comparing results of animal experiments with results of clinical studies. In animal investigations even short hypoxic exposure, continuously or in short repeated episodes mimicking obstructive sleep apnoea (OSA), leads to pulmonary artery remodelling and to pulmonary hypertension (PH). Results of investigations on effects of nocturnal IH on pulmonary haemodynamics in patients with chronic obstructive pulmonary disease (COPD) are discordant. Earlier studies reported the development of mild PH in subjects desaturating during sleep, while more recent investigations did not confirm those findings. Alveolar IH developing during apnoeic episodes during sleep in OSA patients is a disease-induced model to study its effects on pulmonary haemodynamics. In the majority of studies in OSA patients pulmonary arterial pressure remained within normal values. PH was found in patients with OSA accompanied by COPD and/or extreme obesity. People commuting between lowland and high altitude due to their employment, are also repeatedly exposed to IH. Results of clinical investigations suggest that it did not lead to the development of permanent PH. The mechanisms of discrepancies between effects of intermittent hypoxia in animal models and in humans remain to be studied.

Animals↗

TP53 status determines clinical significance of ERBB2 expression in ovarian cancer.

ERBB2 expression has been found in 19 to 44% of ovarian carcinomas; however, its predictive value has not been demonstrated, and trastuzumab has not found clinical application in ovarian cancer patients. We evaluated clinical significance of ERBB2 expression in relation to TP53 accumulation in ovarian carcinoma patients treated with platinum-based regimens. Immunohistochemical analysis with CB11 and a novel NCL-CBE356 antibody (against the internal and external domains of ERBB2, respectively) was performed on 233 tumours (FIGO stage IIB-IV); the US Food and Drug Administration-approved grading system with 0 to 3+ scale was used for evaluation, and the results were analysed by the Cox and logistic regression models. In all, 42% of the tumours expressed (category 1+, 2+ or 3+) either CB11 or CBE356 or both (CB11/CBE356 parameter). Associations between ERBB2 expression and clinical factors were observed only if tumours with staining category 1+ were grouped together with tumours showing staining categories 2+ and 3+. CB11/CBE356 parameter had a better predictive value than CB11 alone. CB11/CBE356 expression was negatively associated with platinum sensitivity (PS) in the TP53(-) group (P=0.022) and with disease-free survival (DFS) in the TP53(+) group (P=0.009). Our results may suggest that trastuzumab should be given postoperatively to patients with TP53(-)/ERBB2(+) ovarian carcinomas to enhance PS, and after completion of chemotherapy to patients with complete remission and TP53(+)/ERBB2(+) carcinomas to extend DFS time (in total to 30.4% of all patients analysed). Thus, novel criteria for ovarian cancer patient inclusion for clinical trials with trastuzumab should be considered and tested.

Adult↗

Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen.

In cell line studies, BCL-2, BAX, as well as novel MEK1 protein levels have strong influence on ovarian cancer response to cisplatin-based chemotherapy. However, such associations have not been demonstrated clinically. We evaluated prognostic/predictive significance of these proteins with regard to TP53 status. Immunohistochemical analysis was performed on 229 ovarian carcinomas FIGO stage IIB-IV treated with platinum-based chemotherapy; the results were analysed by the Cox and logistic regression models. Clinical parameters (residual tumour size, patient age, FIGO stage) were the only indicators of overall survival (OS) and the strongest predictors of complete remission (CR). On the other hand, BAX expression was the strongest (P=0.005) or the only (in FIGO IIIC, P=0.02) prognostic indicator of disease-free survival (DFS) in the TP53(+) group. TP53(+) and TP53(-) ovarian carcinomas differed in clinical and molecular prognostic and predictive factors. Another novel finding is that CR was negatively influenced by high BAX expression in all patients group (P=0.047) and by BCL2 expression in the TP53(-) group (P=0.05). High MEK1 expression was associated with endometrioid and clear cell carcinomas (P=0.049); its loss was found with advancing FIGO stage (P=0.002). Our results suggest that binomial TP53 status divides ovarian carcinomas into two biologically distinct groups. BAX expression is an important factor of DFS in the TP53(+) group. BCL-2 and BAX, but not MEK1 expressions have predictive value in ovarian cancer patients treated with platinum-based chemotherapy.

Adult↗

P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens.

BACKGROUND: The prognostic and predictive value of cell cycle regulatory proteins in ovarian cancer has not been established. We evaluated the clinical and biological significance of P21(WAF1), P27(KIP1), C-MYC, TP53 and Ki67 expressions in ovarian cancer patients. MATERIALS AND METHODS: Immunohistochemical analysis was performed on 204 ovarian carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IV treated with platinum-based chemotherapy. Multivariate analysis with Cox and logistic regression models was performed in the whole group, and in the TP53-negative and TP53-positive subgroups. RESULTS: High P21(WAF1) labeling index (LI) was an independent positive predictor of platinum-sensitive response (P = 0.02). Overall survival was positively influenced by P21(WAF1) LI (P = 0.02) or by P21(WAF1) plus P27(KIP1) LI (P = 0.004) in the TP53-negative group only. Ki67 LI showed borderline association with disease-free survival (P = 0.05). Growth fraction was negatively associated with P21(WAF1) and P27(KIP1) indices in the TP53-negative group (P = 0.023 and 0.008, respectively), and these associations were borderline or lost in the TP53-positive group. Endometrioid and clear cell carcinomas differed from other carcinomas by having a low incidence of TP53 accumulation, a high incidence of C-MYC overexpression (70%) and a low median Ki67 LI (all with P <0.001). CONCLUSIONS: We have shown an independent predictive value of P21(WAF1) LI in ovarian carcinoma patients. The prognostic value of P21(WAF1) and P21(WAF1) plus P27(KIP1) LI was determined by TP53 status. A high frequency of C-MYC overexpression in endometrioid and clear cell carcinomas may suggest its role in the development of these tumor types.

Adult↗

Polish consensus: procedure in case of estrogen deficiency in women after breast cancer therapy.

Women surviving breast cancer in the postmenopausal period suffer from hormonal alternations with adverse effect on mental status and functioning of a number of organs and systems. Two thirds of these women had menopause before the diagnosis of breast cancer. In the remaining one-third ovarian failure is natural or induced by chemotherapy. Doctors cautiously approach the use of estrogen therapy in this group of patients. Their fears are not unsupported bearing in mind known epidemiological data exist linking breast cancer with the use of hormonal therapy. The purpose of this review is to evaluate current data on hormonal use and breast cancer risk.

Breast Neoplasms↗

[Snoring and excessive daytime somnolence and risk of cardiovascular diseases].

Snoring and excessive daytime somnolence (EDS) are very common in middle-age adults. The goal of the investigation was to assess links between those symptoms and risk for cardiovascular diseases (CVD). The population studied included 1186 inhabitants of Warsaw (mean age 52 years), participants of the international multicentre study of cardiovascular disease MONICA II, who completed the sleep disordered breathing (SDB) questionnaire. Snoring was reported by 78% of males (48% habitual and 30% occasional) and 59% of females (27% habitual and 32% occasional). Every fourth (26.8%) subject declared observed apnoeas, in 9.2% apnoeas were observed every night. EDS was declared by 28.7% of studied sample. The results of the questionnaire were compared to the results of MONICA study. Snorers had significantly higher systolic and diastolic blood pressure (133.2 +/- 23/84.6 +/- 13 mm Hg) compared to non-snorers (126.4 +/- 22/80.4 +/- +/- 12 mm Hg) (p < 0.0001). The high total serum cholesterol (> or = 200 mg%) and triglycerides (> or = 200 mg%) concentration, and also obesity (BMI > or = 30 kg/m2) were more prevalent in snorers. Subjects reporting apnoeas more often had coronary artery disease (p < 0.001) or history of stroke (p = 0.002) compared to non-apnoeics. There was no relationship between EDS and risk of cardiovascular disorders, and also between diabetes and SDB. In conclusion, snoring was strongly associated with hyperlipidaemia, obesity or hypertension, well known risk factors for development of cardiovascular disorders. Reported apnoeas were related to risk of coronary artery disease.

Adult↗

[The use of plastic mesh for reconstruction of abdominal wall after surgery for recurrent carcinoma of the cervix].

The experience with the use of plastic mesh for abdominal wall reconstruction after surgery for recurrent carcinoma of the cervix is presented. This method has proved to be effective with an excellent mechanical support for the viscera, with good early and distant morbidity. This technique allowed a subsequent radiotherapy with good tolerance. The presence of abdominal mesh proved not to be a serious obstacle when a secondary surgical intervention is required.

Abdominal Muscles↗

[Effects of spirometric screening in the community on smoking cessation].

UNLABELLED: In the years 1998-2000 in the Centre of COPD and Respiratory Failure in Bydgoszcz a group of tobacco smokers at risk of COPD (over 40 years of age, with smoking history of more than 10 packyears) were studied. Every patient filled-in a simple questionnaire on clinical signs of COPD and tobacco habit, had a spirometry performed according to ATS standards and received a short antitobacco counseling together with a booklet on how to quit smoking. Out of 1072 patients studied in 1998, airway obstruction was found in 200. Eighty seven of these were current smokers (studied group-S). Another 90 current smokers with normal spirometry served as a control group-C. Both groups of smokers were invited in 1999 and 2000 to perform spirometry. Changes in smoking habit were recorded at each yearly visit. After one year 13 patients (15%) from the S group and 4 (4.5%) from the C group permanently stopped smoking. In 2000 24 patients (28%) in S group and 13 (14.7%) in C group permanently quit smoking. CONCLUSION: Spirometric screening in smokers at risk of COPD together with a minimal antismoking intervention seems to be a promising method of smoking cessation.

Adult↗

[Clinical value of polymesam recording in diagnosis of obstructive sleep apnea. Can we replace polysomnography with polymesam?].

UNLABELLED: Polymesam (PM) recordings was performed in 320 patients admitted to Sleep Laboratory with suspicion of OSA. OSA was diagnosed in 179 of them (55.9%), group (PM-Ch). These patients were obese (BMI--34.3 +/- 6.7 kg/m2) and had moderately-severe OSA (RDI--41.5 +/- 19.9 and ODI--43.7 +/- 21.5). They suffered from excessive daytime sleepiness (ESS = 12.2 +/- 5.5). PM was negative in 141 person (44.1%), (PM-Z). Subjects PM-Z had significantly lower BMI and rarely suffered from excessive daytime sleepiness. In 38 subjects PM-Z a full PSG was performed. In 12 PSG confirmed OSA (AHI--31.6 +/- 19.9). Both studies (PM and PSG) were negative in 26 subjects. In 10 obese subjects PM-Ch full PSG confirmed diagnosis. CONCLUSIONS: PM recording can replace full PSG in majority of patients suspected of OSA. Patients with typical symptoms of OSA and negative PM require PSG.

Adult↗

[Ten years experience of the sleep laboratory at the Institute of Tuberculosis and Lung Disease in Warsaw].

Between 1991-2000 2052 patients (81% men and 19% women) were referred to our Sleep Laboratory because of OSA suspision. In 1194 (58%) subjects (88% men and 12% women) diagnosis of obstructive sleep apnoea (OSA, AHI > 10) was confirmed. In 430 of them (36%) mild OSA (AHI 11-25), in 243 (20%) moderate OSA (AHI 26-40), and in 521 (44%) severe OSA (AHI > 40) was diagnosed. Epworth sleepiness scale score in those groups was 10.4, 10.5 and 13.0 points respectively. 908 (76%) of patients with OSA were submitted to nCPAP treatment. Effective CPAP pressure ranged from 5 to 20 milibars, mean 8.4 mbars. In 21 patients upper airway resistance syndrome (UARS) was diagnosed. Central sleep apnoea, most frequently of Cheyne-Stokes respiration type was diagnosed in 13 patients. The most common diseases accompanying OSA were: systemic hypertension (46%), coronary heart disease (29%), diabetes (12%), and COPD (9%). Majority of OSA patients (61%) were obese (BMI > 30 kg/m2), 32% were over weight (BMI 25-30 kg/m2). Only 7% had normal body weight (BMI 20-25 kg/m2). Long-term (more than one year) compliance to treatment was found in 70% of patients prescribed CPAP.

Adolescent↗

[Acromegaly and sleep apnoea syndrome--case report].

We studied 65-year old, obese man suspected of obstructive sleep apnoea. He gave a history of loud snoring and excessive daytime sleepiness. We confirmed sleep apnoea syndrome during limited polysomnography with Polymesam (RDI--45/h, ODI--47/h). Patient had mainly obstructive episodes, however central and mixed apnoeas constituted about 1/3 of all episodes. During hospitalization we observed exacerbation of coronary artery disease and diagnosed diabetes. Patient's coarsened facial features, macroglossia and large hands led us to suspect acromegaly. Brain MR study revealed small pituitary adenoma. Plasma GH and IGF-1 concentrations were increased. Active acromegaly was diagnosed and was proposed a surgical treatment but he refused. Symptoms of sleep apnoea relieved after CPAP treatment. After one year patient's condition remained stable.

Acromegaly↗

[Predictors of success in smoking cessation among participants of spirometric screening for COPD].

The aim of the study was to evaluate factors that could predict smoking cessation after a minimal antismoking counseling during spirometric screening for COPD. Every subject filled-in a simple questionnaire on clinical signs of COPD and tobacco habit, had a spirometry performed according to ATS standards and received a short antitobacco counseling together with a booklet on how to quit smoking. Out of 800 smokers over 40 years of age, smoking history of more than 10 packyears, screened for COPD in 1999, four hundred were invited a year later for a follow-up spirometry and evaluation of anti-smoking intervention. Of 383 patients, who responded to the invitation (208 M and 175 F, mean age 56.6 +/- 10.7 yrs), 52 (13.6%) quit smoking for one year and another 48 (12.5%) quit smoking temporarily and than resumed smoking. Smokers who permanently succeeded in quitting smoking were older (60.5 vs 55.9 years p < 0.01), started smoking later (age at starting smoking 22 vs 19.5 years p < 0.001), had a shorter tobacco exposition (28.8 vs 34.3 packyears p < 0.05), had lower lung function (FEV1%pred 80.5 vs 89.2% p < 0.05) and were less nicotine dependent (FTQ score 1 vs 4.8 p < 0.00001).

Adult↗

[Awareness of airflow obstruction together with antismoking advice increases success in cessation smoking].

COPD is one of the leading causes of mortality and increased morbidity in developed world. In advanced disease it also imposes an important economic burden on societies. The main etiologic factor for COPD is tobacco smoking. The aim of the study was to asses if the awareness of airflow obstruction combined together with a minimal antismoking advice in middle aged smokers increases the quitting rate. Out of smokers participating in mass spirometric screening for COPD in five polish towns, we invited 734 (300 with airflow limitation and 247 with normal lung function) for a follow-up. During the second visit, at one year, spirometry was performed and smoking status was assessed. Non-smoking was validated with carbon monoxide measurements in exhaled breath. Patients who did not come for the follow-up visit were considered as smokers. Of 734 smokers invited, 543 (74%) presented for the follow-up visit. All smokers tried to modify the habit. Number of cigarettes smoked at one year was reduced by -5.5 (p < 0.001) in patients with airflow limitation and -2.2 (ns) in smokers with normal lung function. One year quit rate in smokers with airflow limitation was 11.1% vs 7.6% in smokers with normal lung function (ns). When the calculation was made for those who had the follow-up the quit rates were 15.1% vs 9.9% (p < 0.05). Cessation of smoking was correlated with lung function. Those smokers who stopped smoking permanently or tried to quit had lower FEV1 (p < 0.01) and FEV1/FVC (p < 0.05), than those who continued to smoke.

Adult↗

The quality of sleep and periodic breathing in healthy subjects at an altitude of 3,200 m.

The medical risks of travel and stay at high altitude are well known. Many more people travel for recreation to lower but still significant altitudes. To investigate the quality of sleep and sleep-related breathing disorders (SRBD) at that altitude we performed full polysomnography in nine young volunteers at lowland (760 m above sea level) on the first and sixth night after ascent to 3,200 m. There have been few studies on such populations. The subjects were nonsmoking healthy males aged 20.3 +/- 3.5 years with normal spirometry and arterial blood gas measurements performed at low altitude. Although there was no statistically significant difference in the duration of stages and sleep quality between low altitude night and both nights at high altitude as assessed by percent of sleep spent in stage 1, 2, 3+4 NREM, and REM sleep, total sleep time (TST), and sleep efficiency; the number of arousals and awakenings doubled at high altitude. There was no periodic breathing (PB) during sleep, except in isolated central events of SRBD, at low altitude. PB appeared at altitude mostly during NREM sleep and its intensity remained stable throughout the study period. Individual variations of PB intensity were high, ranging from 0.1 to 24% of TST. There were also some episodes of obstructive apnea and hypopnea during sleep at high altitude (p < 0.001). Mean SaO2 was lower during the study nights at high altitude when compared with low altitude. There were some signs of ventilatory acclimatization as shown by a higher mean SaO2 during the sixth compared with the first night at altitude (p < 0.001). We conclude that the sleep quality at the altitude of 3,200 m remains satisfactory when compared to low altitude. There is high individual variability in intensity of PB at that altitude.

Acclimatization↗