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Biomedical subjects

J Nowak

Publications and source records attributed to J Nowak.

At least 73 records · Page 4Linked to original sources
PubMed1996

Thromboxane metabolite excretion in patients with hand-arm vibration syndrome.

As chronic exposure to hand-held vibrating tools may cause endothelial injury, a subsequent sustained platelet activation with the increased release of vasoconstricting thromboxane A2 (TxA2) could be of pathophysiological importance in vibration-induced Raynaud's phenomenon. Therefore, the aim of this study was to elucidate whether or not hand-arm vibration syndrome is accompanied by increased endogenous TxA2 biosynthesis. The study involved 64 men, aged 23-61 years, stratified according to the exposure to vibrating tools, the presence of Raynaud's phenomenon, and smoking habit. Forty of them were car mechanics and 24 were age-matched healthy volunteers who served as controls. The assessment of platelet TxA2 formation in vivo was performed by quantification of the urinary excretion of its major metabolite, 2,3-dinorthromboxane B2 (2,3-dinor-TxB2), employing gas chromatography-mass spectrometry. The average urinary excretion rate of 2,3-dinor-TxB2 in patients with Raynaud's phenomenon was 296 +/- 42 pg/mg creatinine and did not differ significantly from the corresponding values in controls (328 +/- 62 pg/mg creatinine) or individuals exposed to vibrating tools, but without any signs of vasospastic disease (232 +/- 29 pg/mg creatinine). The only statistically significant difference was found between smokers and non-smokers (P < 0.001), a finding confirming the existence of chronic platelet dysfunction in cigarette smokers. The present data indicate that chronic exposure to vibrating tools, with or without Raynaud's phenomenon, is not associated with an enhanced platelet function as monitored by the urinary excretion of 2,3-dinor-TxB2. Hence, a possible vibration-induced vascular injury does not seem to provide a stimulus sufficient to induce a persistent platelet activation.

Adult↗
PubMed1996

Chaos-related deterministic regulation of heart rate variability in time- and frequency domains: effects of autonomic blockade and exercise.

OBJECTIVES: To study non-linear complexity or chaotic behaviour of heart rate in short time series and its dependence on autonomic tone. METHODS: Ten healthy individuals (5 men, mean age 44 years) were investigated at rest, after intravenous injections of propranolol (0.15 mg/kg), followed by atropine (0.03 mg/kg). On another occasion, investigation was made during exercise on a bicycle ergometer at 40% and at 70% of maximal working capacity. Heart rate variability was assessed by: local sensitive dependence on initial conditions as quantitated by the dominant Lyapunov exponent, coefficient of variation of heart rate, power spectral analysis of high- and low-frequency bands and the 1/f-slope of the very-low-frequency band and time domain analysis. RESULTS: The approximate dominant Lyapunov exponent was positive at rest and remained positive during autonomic blockade and during exercise. The exponent decreased significantly with propranolol+atropine and even more so during exercise but did not attain zero. At baseline approximate predictability was lost after about 30 s whereas after autonomic blockade or exercise it was lost after about 60 s. The 1/f-slope remained unaltered around -1. As expected, power in high- and low-frequency bands as well as time domain index decreased significantly with autonomic blockade. The low-frequency band and time domain index were affected by exercise. CONCLUSIONS: Heart rate variability of sinus rhythm in healthy individuals has characteristics suggestive of low-dimensional chaos-like determinism which is modulated but not eliminated by inhibition of autonomic tone or by exercise. The dominant Lyapunov exponent characterises heart rate variability independent or the other investigated measures.

Adult↗
PubMed1996

Long-term Cyclosporine A (Sandimmun) therapy for steroid resistant nephrotic syndrome in children.

The aim of the paper was to evaluate Cyclosporine A (CsA) treatment in children with steroid resistant nephrotic syndrome (diagnosed according to criteria established by ISKDC), in whom numerous attempts at other types of therapy had failed. CsA was used in 23 children aged 2-16 years. Renal biopsies revealed minimal changes (MCD) in 7 children, focal segmental glomerulosclerosis (FGS) in 11, mesangial glomerulonephritis (MES) in 4, and membrano-proliferative glomerulonephritis (MPGN) in 1. CsA was administered for a period of 6-41 months at a daily dose of 6 mg/kg, gradually decreased to 2.5 mg/kg. Blood CsA level was 40-200 ng/ml. In the course of the treatment, proteinuria disappeared or diminished and clinical improvement was seen in 21 patients. 13 children had relapses of nephrotic syndrome, showing very low blood CsA levels. Complete remissions were achieved in 16 children, partial remissions in 5, no remission in 2. Throughout the treatment and after its cessation 22 patients manifested no deterioration of renal function. In 1 child, repeated renal biopsies revealed some lesions that could suggest a nephrotoxic effect of CsA. Secondary steroid sensitivity observed in 3 children should be emphasized. Concluding, CsA is an effective and well tolerated agent in children with steroid resistant nephrotic syndrome, and the improvement noted in patients with FGS may reduce the risk of early terminal failure. The treatment requires monitoring blood CsA levels.

Adolescent↗
PubMed1996

[Evaluation of platelet membrane structure in patients with chronic glomerulonephritis (CGN)].

The structure of platelet membrane determines platelet surface glycoprotein receptors and correct cell function. Meanwhile different diseases and drugs may induce changes in this structure. The aim of this study was to determine structure of platelet lipid bilayer in patients with chronic glomerulonephritis (CGN) in comparison to control group. Studies were carried out in 30 patients with nephrotic syndrome (NS) and 30 patients without this syndrome and 15 controls. Electron spin resonance phenomenon with spin labelling, was used for estimation of platelet membrane structure. CGN patient platelets showed lower order parameter A/C and increased rotation correlation time tau in comparison with healthy subjects. It indicated abnormal platelet membrane structure in these patients. The negative significant correlation between parameter A/C and plasma fibrinogen concentration of NS patients has been found (r = -0.5; p < 0.05). Additionally the value of an order parameter (A/C) has significantly positively correlated with serum triglycerides concentration in patients with NS and spontaneous platelet aggregation (r = 0.52, p < 0.05). Conclusion. 1. CGN patient platelets have revealed disorders of lipid bilayer structure. 2. These disorders could be responsible for decreased platelet aggregation observed in CGN patients in comparison to healthy controls.

Adult↗
PubMed1996

[Congenital heart defects in adolescence and adulthood: fatalities and morbidity in primary and reoperation].

Adolescents and adults with congenital heart disease have become a new, continuously growing group of patients, because currently improved diagnostics and therapy allow the majority of newborns with congenital heart disease to survive to adulthood. The objective of this retrospective study was to investigate lethality and morbidity after surgery for congenital heart disease in adolescents and adults. Between 1989 and 1994, we operated 137 patients (age between 15 and 75 years; mean 33.8 +/- 15.1) because of congenital heart disease. This was equivalent to 2.7% of all patients, who were operated during this period of time. 101 cases were primary operations, in 36 cases (26.3%) a reoperation was performed. The most frequent diagnoses were ostium-secundum-defect (37.9%), anomalies of the aortic valve including sub- and supravalvular stenoses (9.5%), anomalies of the mitral valve (8%), ventricular septal defect (7.3%) and aortic coarctation (7.3%). Overall lethality was 5.8%, including emergency cases and all late deaths, which have been reported so far. Evaluation of morbidity showed an intraoperative cardiac low-output-syndrome in 3.7%, pulmonary failure in 5.8%, postoperative renal failure in 4.4% and postoperative bleeding complications in 7.3% of cases. Mean duration of postoperative ventilation and intensive care treatment were 2.3 +/- 5.3 and 3.6 +/- 7.3 d, respectively. In comparison to their preoperative status, 71% of patients had improved by one or two NYHA classes. We found that the higher perioperative risk related to reoperation had no impact on the operation's functional result, as evaluation of postoperative functional class showed no difference between primary and re-do cases. The general term congenital heart disease describes a very inhomogeneous group of patients with a broad spectrum of different diagnoses. The variable morphology and pathophysiology of the different congenital heart defects require an individual surgical strategy for each patient, in rare cases even the decision for a heart- or heart-lung-transplantation. Furthermore, adequate follow-up and competent ambulatory treatment of these patients require the cooperation of pediatric and adult cardiologists and cardiac surgeons in interdisciplinary outpatient clinics.

Adolescent↗
PubMed1996

[The effect of administering Omega-3 acids on lipids in serum, functional state of erythrocyte membrane and function of the kidneys in patients with primary glomerulonephritis].

There are reports concerning profitable influence of unsaturated acids administration on blood pressure, inflammation and proteinuria. The aim of presented study was to estimate the effect of Omega-3 on plasma lipids and renal function in patients with primary glomerulopathies. The tested group consisted of 13 patients (7F and 6M) aged from 22 to 60 years, with primary glomerulopathies and normal renal function. They received Omega-3 (Fishproduct, iceland) 3 x 2 caps for three months. Before, after 2 and 3 months of treatment and 3 months after its discontinuation following parameters were estimated: total cholesterol, HDL and LDL cholesterol (HDL, LDL), triglycerides and an order parameter of erythrocyte lipid bilayer (S). Simultaneously N-acetylglutamate (NAG), creatinine clearance and 24-hours proteinuria were measured. For calculation t-Student test was used. In our study we found statistically significant increase of HDL after 2 and 3 months and decrease of LDL after 3 months of Omega-3 administration (p < 0.05). During the 2 and 3 months of treatment statistically significant decrease of NAG was noticed but a month after its discontinuation significant increase of NAG excretion was observed (p < 0.05). The S parameter in tested group of patients was higher than in healthy population but during Omega-3 administration the value of an order parameter of erythrocyte bilayer increased significantly (p < 0.01). On the base of given results we could conclude that unsaturated acids may have profitable influence on plasma lipids, functional status of erythrocyte membrane and probably proximal tubule function in patients with primary glomerulopathies.

Adult↗
PubMed1995

The delayed-type hypersensitivity reaction is dependent on IL-8. Inhibition of a tuberculin skin reaction by an anti-IL-8 monoclonal antibody.

Cell-mediated immune reactions are essential to our immune response toward foreign organisms such as microorganisms, or in the response toward foreign tissue Ags, as seen in the rejection of allogeneic transplanted organs. Similar reactions form the basis for the development and the progression of delayed-type hypersensitivity (DTH) reactions. We found that the alpha-chemokine IL-8 plays an important pathophysiologic role for the development of a DTH reaction because infusion of a neutralizing anti-IL-8 mAb (WS-4) was able to suppress the development of a tuberculin skin reaction in rabbits, as judged by histologic, biochemical, and clinical examinations. Thus, the number of neutrophil granulocytes and lymphocytes at the site of tuberculin injection was decreased considerably, and the clinical signs of inflammation were suppressed almost completely at 24 h after intracutaneous injection of tuberculin, as judged by the size of the infiltrates. In contrast, we did not see any effect on the visible erythema of the skin. We found that the tissue content of myeloperoxidase (MPO), reflecting the number of infiltrating neutrophils, was lowered significantly. Furthermore, immunohistochemical analysis confirmed that IL-8 immunoreactivity is actually enhanced in the skin of positive tuberculin reactions. The results indicate that IL-8 plays an important role for the early accumulation of leukocytes in the skin and for the clinical signs of a DTH reaction.

Animals↗
PubMed1995

Interleukin-6-type cytokines and their receptors for gene therapy of melanoma.

B-78-H1 melanoma cells were stably transfected with cDNAs encoding human IL-6, human LIF, murine sIL-6R and murine sLIFR. The mock transfected and transfected cells demonstrated no detectable H-2Kb molecules. B-78 transfected cells were subcutaneously (s.c.) and intravenously (i.v.) injected to B57BL/6 x C3H mice. Control B-78 cells formed tumors and lung metastases in injected animals. Cells transfected with IL-6, LIF and sIL-6R showed greatly reduced tumor and metastases formation. Transfection of IL-6, sIL-6R or LIF had similar protective effects while the combination of IL-6 and sIL-6R was most effective. In contrast, cells transfected with sLIFR showed reduced metastasis formation but increased tumor growth compared to mock transfected cells. Kinetic analysis demonstrated a 3 weeks lag period between the formation of tumors by B-78 cells and the combination of B-78 cells transfected with IL-6 and sIL-6R. No such lag phase was seen when B-78-IL-6 or B-78-sIL-6R cells were injected alone. Mice primarily injected s.c. with a mixture of IL-6 and sIL-6R transfected cells and rechallenged after 2 weeks with parental B-78 cells demonstrated long-lasting antitumor immunity. IL-6 and sIL-6 transfected cells used alone for immunization had only limited effect. Injection of transfected cells into SCID mice which are characterized by greatly reduced number of T and B cells, showed a protective effect of sIL-6R on metastasis formation by B-78 cells. beta 2m knockout mice lacking CD8+ T cells, injected with B-78 cells developed tumors and died after 2 weeks. However, B-78 cells transfected with IL-6 developed tumors in only 50% of animals. Mice without tumors rechallenged with B-78 cells demonstrated required immunity against parental melanoma cells. The results obtained indicate that studied IL-6-type cytokines and their respective soluble receptors affect murine melanoma growth and metastasis formation. The major finding of these studies is that IL-6 complexed with sIL-6R demonstrated qualitatively different biological activity than IL-6 alone especially in stimulating long lasting anti-melanoma immunity. The proposed mechanism of action of such complexes beside activation of cytotoxic T lymphocytes is activation of NK cells.

Animals↗
PubMed1995

Soluble interleukin 6 receptor is biologically active in vivo.

A cancer cell transfection model was used to evaluate biological activity of soluble IL-6 receptor (sIL-6R) in vivo. B-78 melanoma cells were stably transfected with cDNAs encoding human IL-6, murine sIL-6R and human leukaemia inhibitory factor (LIF). Control and transfected cells were intravenously (i.v.) and/or subcutaneously (s.c.) injected into B57BL/6 x C3H or SCID mice. Whereas B-78 cells formed tumours and lung metastasis in injected animals, transfected animals, transfected cells showed greatly reduced tumour and metastasis formation. Transfection of IL-6, sIL-6R or LIF had similar protective effects. The combination of IL-6 and sIL-6R was most effective. Kinetic analysis demonstrated a 3 week lag period between formation of tumours by B-78 cells and the combination of B-78 cells transfected with IL-6 and sIL-6R. No such lag phase was seen when B-78-IL-6 or B-78-IL-6 or B-78-sIL-6R were injected alone. These results indicate that IL-6 alone exhibits a different quality of activity when compared to the IL-6-soluble receptor complex. Our results demonstrate for the first time that sIL-6R is a biologically active molecule in vivo.

Animals↗
PubMed1995

24-h ECG monitoring in patients with rheumatoid arthritis.

Although the main cardiac complication in patients with rheumatoid arthritis is subclinical pericarditis, mononuclear cell infiltrations into myocardium may cause cardiac arrhythmias and conduction defects. In order to examine these problems we evaluated 70 patients (53 women and 17 men) aged 18-83 years (average 56.7 +/- 11.2) with classic or definite rheumatoid arthritis, according to diagnostic criteria. Duration of the disease was 1-35 years (average 8.7 +/- 8.4). The control group comprised 70 patients admitted to hospital with degenerative joint disease, a duodenal ulcer, or who required treatment for ophthalmological or laryngeal reasons; these patients were matched for sex and age. In all patients standard 12-lead ECG investigations were performed, as well as 24-h ECG monitoring, using an Oxford Medical System device with two precordial leads CM5 and CS2, according to the Holter method. We analysed heart rate, conduction disturbances, and occurrence of arrhythmias, on the basis of generally assumed ECG criteria. Cardiac arrhythmias were found in 50% of patients with rheumatoid arthritis, and their occurrence was similar to that in the control group. Observed arrhythmias were independent of the progression of arthritis, the type of treatment administered, the familial occurrence of arthritis, the presence of manifestations pertaining to organs, the presence of rheumatoid factor, the stage of the disease according to Steinbrocker, or the presence of immune complexes in serum and HLA Dr antigens, which are regarded as fundamental in the pathogenesis of rheumatoid arthritis.

Adolescent↗
PubMed1995

Aluminum sensitivity of loblolly pine and slash pine seedlings grown in solution culture.

To probe variation in Al sensitivity of two co-occurring pine species, seedlings from six full-sib families of loblolly pine (Pinus taeda L.) and slash pine (Pinus elliottii Engelm.) were grown in solution culture containing 4.4 mM (high-Al) or 0.01 mM (low-Al) AlCl(3) at pH 4 for 58 days. On average, both pine species had 41% less total dry weight in the high-Al treatment than in the low-Al treatment. Stem volume growth of slash pine was more sensitive to the high-Al treatment than that of loblolly pine. In both species, the high-Al treatment inhibited root dry weight more than shoot dry weight. Within-species variation in Al sensitivity among families was greater in loblolly pine (24 to 52% inhibition of seedling dry weight) than in slash pine (35 to 47% inhibition of seedling dry weight). Foliar Al concentration was positively correlated with Al sensitivity in slash pine but not in loblolly pine; however, in both species, the concentration of Al in roots was 20-fold greater than in foliage.

Journal Article↗
PubMed1995

[Treatment of multiple myeloma associated anemia with human recombinant erythropoietin in a hemodialysis patient].

Recombinant human erythropoietin (rHuEPO) was used to treat the anaemia in a hemodialyzed 60 year old man with multiple myeloma requiring chemotherapy; the type of serum M component was IgA kappa. During the 5 months before rHuEPO treatment the patient was given multiple blood transfusions. rHuEPO was started 125 U/kg/week subcutaneously in divided doses after dialysis. After introduction of rHuEPO, blood transfusions were no longer required and haemoglobin concentration increased from 5.2 mmol/l to 6.9 mmol/l after 8 weeks of treatment. We conclude that rHuEPO treatment in haemodialysed patients with multiple myeloma may be safe, well tolerated and clinically effective.

Anemia↗
PubMed1995

Verapamil influences the effect of nonionic contrast agent on platelet membrane structure and aggregation.

Anticoagulant and antiplatelet function of NICM is weak, thereby presenting a hazard of coronary thrombus growth in patients subjected to coronary angiography. Similar antiplatelet effect was demonstrated for verapamil (V). The present study was designed to determine iopromide induced modifications in blood platelet membrane structure and aggregation in patients with primary hypertension and ischaemic heart disease receiving V compared to non-receivers of V. The blood for examinations was collected by Judkins' catheter placed in the vicinity of the coronary vessel ostium, and next centrifuged to obtain platelet-rich plasma. The ADP- and ristocetin (R)-induced blood platelet aggregation was determined by means of an aggregometer while their membrane structure was studied by electron paramagnetic resonance. The spin-label used, 4-maleimide-2, 2, 6, 6-tetramethyl-piperidine-1-oxyl (MSL) binds covalently to the -SH and -NH2 groups of platelet membrane proteins. The modifications in various spectral components, examined by means of a spectrometer, reflect conformational changes in these proteins. In non-receivers of V, iopromide diminished the aggregation, significantly in the case of ADP (p = 0.05), whereas in the receivers of V the iopromide-induced platelet aggregation examined with ADP did not change while with R was even enhanced (p = 0.05, Fig. 2). The platelet membrane protein conformation also changed due to iopromide: in non-receivers of V the accessibility of the above named groups for MSL was significantly reduced, p < 0.05, but in the receivers of V--inversely--significantly increased, p < 0.05. The results obtained confirm that in non-receivers of V, iopromide modifies the conformation of platelet membrane proteins which, in turn, may result in the lessening of the aggregation rate, favourable as regards the conditions of coronary thrombus growth. The tendency in the receivers of V was reverse and, however its nature remains obscure, this effect should be an indication for discontinuing the use of V several days before subjection the patient to coronary angiography.

Calcium Channel Blockers↗
PubMed1994

Variance ECG detection of coronary artery disease--a comparison with exercise stress test and myocardial scintigraphy.

Variance electrocardiogram (ECG) is a newly developed method by which resting ECG is registered with 24 leads during 220 beats. The temporal beat-to-beat QRS microamplitude variability is computed and a nondimensional diagnostic variance ECG coronary artery disease (CAD) index is derived from it. Consecutive outpatients (n = 160) were referred to myocardial scintigraphy (SPECT) investigation for the evaluation of angina pectoris. The variance ECG CAD index was compared with a symptom-limited exercise stress test and SPECT during and after the exercise test and with coronary angiography (n = 67). Discriminant accuracy was tested with receiver-operating characteristics (ROC). Relative to angiographic coronary pathology (prevalence 0.85), diagnostic information for the variance ECG CAD index and for SPECT were both p < 0.001, while the outcome of the exercise stress test was non-contributory. Prevalence of persistent or transient perfusion defects at SPECT was 0.59. The exercise stress test had a diagnostic capacity of p < 0.01 for transient perfusion defects and variance ECG CAD index showed a high diagnostic performance (p < 0.001) for persistent perfusion defects. Overall pathology at SPECT was better (p < 0.05) identified by variance ECG CAD index than by symptom-limited exercise stress test. It was concluded that in this high prevalence population the variance ECG CAD index has a diagnostic capacity at least as good as that of SPECT and better than that of the exercise stress test. The variance ECG CAD index was strongly diagnostic for persistent perfusion defects while exercise stress test was slightly diagnostic for transient perfusion defects. Therefore, the two tests provide complementary diagnostic information.

Adult↗
PubMed1994

Different pattern of T cell receptor delta gene rearrangement in tumour-infiltrating lymphocytes and peripheral blood in patients with solid tumours.

Tumour-infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) from four patients with renal-cell carcinoma (three paired with blood), two colon carcinomas (both paired with blood) and two melanomas (blood was not available) were analysed for the T cell receptor (TCR) delta gene repertoire. Polymerase chain reaction analysis, employing a panel of specific primers for TCR delta gene segments, showed different gene rearrangement patterns in TIL and PBL in all patients. Simultaneous analysis of TIL and PBL revealed the presence of lymphoid cells in the tumour tissue that were not present in the periphery. These results demonstrate that, although tumour-infiltrating lymphocytes contain gamma/delta T cells within the range observed in peripheral blood, these cells differ from those in peripheral blood in their gene repertoire and this may account for selective accumulation or/and in situ amplification of gamma/delta lymphocytes at the tumour site, indicating a unique type of host reaction against tumour.

Base Sequence↗
PubMed1994

Signal variance electrocardiogram: a test for early detection of myocardial involvement in cystic fibrosis?

1. Variance electrocardiography is a new resting procedure for the detection of ischaemia-induced variability in the electrical expression of the depolarization phase. The analysis is performed on 220 cardiac cycles using high-fidelity ECG signals from 24 leads, and the electrical variability is expressed as an electrical variability index ranging from 1 to 150. In this study, variance electrocardiography was employed to detect cardiac involvement in 23 patients with cystic fibrosis. 2. Patients with cystic fibrosis presented a significantly higher mean electrical variability index than control subjects, and their index values correlated inversely with the arterial oxygen partial pressure and forced expiratory volume in 1.0 s. Patients with a high electrical variability index (> 75) displayed a lower clinical score (Shwachman score) and a longer duration of chronic colonization with Pseudomonas aeruginosa. Patients with conduction disturbances and patients with echocardiographic right ventricular pathology presented higher indices than those without. 3. Electrical variability index is increased in cystic fibrosis and correlates with other signs of cardiac and pulmonary derangement. Variance electrocardiography may therefore have the potential to be a sensitive and simple method for monitoring cardiac involvement in this disease.

Adult↗