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Biomedical subjects

Przemysław Rutkowski

Publications and source records attributed to Przemysław Rutkowski.

12 recordsLinked to original sources

Interrelationship between uremic toxicity and oxidative stress.

Uremic syndrome is associated with several metabolic disturbances. Oxidative stress is an important factor involved in the pathologic mechanism of these changes. The goal of this study was to understand the relationship between oxidative stress markers and two compounds included among uremic toxins. Two independent studies were performed, one with 29 peritoneal dialysis patients and the other with 43 predialysis subjects. In both groups of patients, known oxidative stress markers, malonyldialdehyde (MDA) and carbonyl groups (CG) formation were measured. Additionally, in the predialysis group, glutathione in erythrocytes (GSH) was estimated. In peritoneal dialysis patients, the concentration of advanced glycation end products (AGEs) was found to be significantly increased and correlated with both markers of oxidative stress. In predialysis patients, the increment of newly described uremic toxin purine nucleotide end products (Me2PY and Me4PY) were found and significant correlation was observed between both compounds versus MDA (positive) and GSH (negative). This relationship was visible especially in patients with more advanced renal failure. CG concentration was within the normal values and did not show any correlation with estimated toxin concentrations. In summary, results of both studies suggest that the interrelationship between uremic toxicity and oxidative stress is an important component of uremic syndrome. Nevertheless, further complex studies are needed to elucidate closer pathogenic links.

Aged↗

[Clinical and metabolic consequences of uremic toxicity].

Retention of many substances takes place in the pathogenesis of uremic toxicity. There are almost 100 different molecules described and defined as uremic toxins. These substances are divided into three groups according to EUTOX group calssification. Small water soluble molecules with a molecular weight less than 500 D are included into the first group. Derivate of guanidines, purines, pyrimidines and methyloamines appeared in this group. There is also an unclassified subgroup with urea as a "classical" toxin which the real role in the uraemic syndrome is still discussed. Main symptoms caused by these molecules are digestive disturbances, neurological changes, hypertension etc. We can eliminate almost all of these toxins with standard methods used during dialysotherapy. Substances with a different molecular weight but connected with proteins determine the second group. AGE-s, phenol derivates, leptin and poliamines beside others create this group. There are many studies that have proved that these toxins cause hypertension, arteriosclerosis and shortened life time of hemodialysed patients. However, melatonin toxicity is not fully proved. Different types of renal replacement therapy are not valid to purify blood from protein-bound substances. Middle molecules are included into the third group, with a molecular weight higher than 500 D. There are cytokines, neuro-transmitters e.g. beta-endorphin, metencephalin and many others accounted into this group. One of them is the parathormon, well known and considered as "universal" toxin for several years. Middle molecules are causing very different effects. They are responsible for: anemia, arteriosclerosis, chronic inflammation and generally increase dialysed patient mortality. Toxic action of several molecules described below is still not proved; however there are some ongoing studies aimed to find pathophysiological links between old and new described uremic toxins.

Hemodialysis Solutions↗

Randomized, controlled study of the effects of losartan versus enalapril in small doses on proteinuria and tubular injury in primary glomerulonephritis.

BACKGROUND: Pharmacological blockade of the renin-angiotensin-aldosteron system ameliorates glomerular and tubulointerstitial damage. For optimal renoprotection, high doses of angiotensin II converting enzyme inhibitors and angiotensin II subtype 1 receptor antagonists are commonly recommended, but cannot always be administered. The aim of this study was to evaluate the effects of low-dose (25 mg) losartan on proteinuria and tubular injury extent. MATERIAL/METHODS: This was an open, randomized, 12-month study on the effects of 25 mg of losartan (n=19) vs. 10 mg of enalapril (n=14) as a control on proteinuria, urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), and blood pressure in patients with primary glomerulonephritis. The second part of the study was an uncontrolled assessment of the renal effects of 50-mg administration of losartan. RESULTS: There were no significant differences between the groups in the effects on proteinuria and NAG excretion. Losartan and enalapril reduced proteinuria by 32.8% (p<0.029) and 40.9% (p<0.021), respectively, but did not affect NAG excretion. The antiproteinuric effect of losartan, achieved without changes in blood pressure, was particularly evident in subjects with proteinuria >1.5 g/24 h and normal blood pressure. 50 mg of losartan caused a significant decrease in NAG excretion vs. the baseline (p<0.027). CONCLUSIONS: 25 mg of losartan and 10 mg of enalapril equally reduce proteinuria. The significant antiproteinuric effect of losartan was achieved despite no changes in blood pressure. There were no differences between the drugs regarding their influence on tubular injury extent. 50 mg of losartan seems to be the minimal dose to improve tubular status.

Adult↗

Enzymatic examination of potential interaction between statins or fibrates and consumed Tricholoma equestre.

The enzymatic investigations were done in 56 patients, including 30 females and 26 males in the age range 18-76 (mean 52 +/- 12). Thirty two of them (57.1%) suffered from type 2 diabetes. All the patients consumed voluntarily Tricholoma equestre; 43 of them only once from 70 to 150 g, and 13 patients from two to four times for 4 consecutive days (between 300 g and 1200 g). Twenty seven patients, because of hyperlipidemia, took statins (simvastatin á 20 mg--15 patients, lovastatin á 20 mg--6 patients, fluvastatin á 80 mg--3 patients, atorvastatin á 20 mg--3 patients) and seven took fibrates (4 patients-- enofibrate á 267 mg, and 3 patients--ciprofibrate á 100 mg). Two subjects ingested both simvastatin á 20 mg and fenofibrate á 267 mg. Three to six days after the last mushroom dish, blood samples were taken from patients to examine the serum creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. The biochemical analyses were performed by means of the kinetic spectrophotometry using the autoanalyzer Architect ClI8200 with Abbott proprietary reagents. Statistical analysis was performed by means of t-Student test. Tricholoma equestre taken by patients in a total amount from 70 g to 1200 g for four consecutive days did not cause the significant increase in serum CK, AST, ALT activities. Similar mushroom dishes consumed by patients constantly using statins or fibrates also did not increase significantly the serum CK, AST, ALT activities. Patients treated with statins or fibrates may eat Tricholoma equestre in reasonable amount according to the established tradition.

Adult↗

Regression of long standing anorexia nervosa following acute renal failure caused by gentamicin intoxication.

A female patient aged 22 with fully developed symptoms of anorexia nervosa presented the following metabolic disturbances: persistent hyperuricemia, hyponatruria, (sometimes with sodium lack in urine) as well as frequent hyponatremia and hyper-uricosuria. The patient's low arterial blood pressure (70/40 mm Hg on average) was not improved by pharmacological treatment, and only high oral doses of table salt (20-70 g/24 h) did prove effective in the therapy. The subject passed seven renal calculi composed of sodium urate and uric acid. Numerous urinalyses did not reveal any changes, and bacterial cultures of the urine were also negative. After 14 years of anorexia nervosa, the patient was treated for pneumonia with gentamicin at doses of 2 x 80 mg/24 h. Following third dose of the antibiotic, the patient developed acute renal failure and was treated by haemodialysis for six weeks. The renal function came gradually to the norm. Simultaneously, all the anorexia nervosa symptoms subsided along with sodium metabolism disturbances, while purine metabolism disorders got considerably alleviated. The patient started to have her menstrual cycles again, gained 12 kg in body weight, and one year afterwards bore a son. A further 10-year follow-up period was free of any pathological changes except for a slight hyperuricemia. To the best of our knowledge, the similar case has not been reported in the medical literature and electronic data bases.

Acute Kidney Injury↗

[Heart and kidneys].

During last fifty years several investigations were performed enabling detection and description of close relationships between kidneys and heart. It is dealing both with connections important for maintenance of homeostasis and with pathological disturbances. On the other hand there are no doubts that chronic kidney diseases, and especially their chronic failure, are connected with development of deep cardio-vascular changes. This interrelationship is becoming more clear when similiarities between factors causing progress of renal failure and development of cardio-vascular changes on the othe hand are concluded. So the main important issue is early prevention and after recognition of their existence early specific therapy.

Comorbidity↗

Disturbances of purine nucleotide metabolism in uremia.

The increased concentration of adenosine triphosphate (ATP) in erythrocytes from patients with chronic renal failure (CRF) has been observed in many studies but the mechanism leading to these abnormalities still is controversial. It is believed that hyperphosphatemia and metabolic acidosis triggering enhanced reutilization of purine bases are the factors responsible for changes in erythrocyte nucleotide concentration. During the past decade we have performed several studies. A summary of the obtained results is presented. A high-performance liquid chromatography technique was used for the determination of plasma and intraerythrocyte nucleotide concentrations. Labeled adenine and adenosine were used for measuring adenine incorporation. In CRF patients treated conservatively increased concentrations of ATP levels and other nucleotides such as adenosine diphosphate were found. Adenosine monophosphate and hypoxanthine levels were lower than in controls. In hemodialyzed patients both ATP and adenosine monophosphate intraerythrocyte concentrations were higher than in controls. At the same time, adenosine monophosphate and hypoxantine level were comparable with levels in healthy people. The main pattern of nucleotides during hemodialysis remained unchanged, independent from the mode of therapy. The only exception was a decreased level of hypoxantine. Results of a consecutive study have suggested that the increased rate of adenine incorporation into the adenine nucleotide pool could be partially responsible for the increased ATP concentration in uremic erythrocytes. Last but not least, trying to elucidate the pathomechanism of adenine nucleotide disturbances in uremia, we have found that the concentration of N-methyl-2-pyridone-5-carboxamide (2PY), one of the end products of nicotinamide-adenine dinucleotide degradation, were enhanced in CRF patients to values that are potentially toxic. Our findings suggest that 2PY could be a novel uremic toxin. Disturbances of nucleotide metabolism are one of the important components of uremic syndrome.

Adenosine Triphosphate↗

[Clinical and mycological examinations of oral mucosa in cyclosporine A treated patients after renal transplantation].

Cyclosporine A (CsA) is one of the basic and often used immunosuppressive agents. It is used to prevent rejection of allogenic transplants and to cure many diseases with autoimmunological components. The development of transplantology and frequent presence of autoaggressive disorders causes increased use of CsA, which intensifies problem of side-effects. Gingival overgrowth, oral mucosa pathologies related with bacterial, viral and fungal infections and neoplasma are described as most frequent side-effects of cyclosporine A in the oral cavity. The aim of this study was to assess the frequency of presence of different types of oral mucosa lesions in cyclosporine A-treated patients after renal transplantation. Thirty renal transplant recipients aged 11-64 years (including 13 females and 17 males) with cyclosporine treatment period from 6 months to 10 years were examined. Pathological changes on the oral mucosa were noted in 18 patients (60%). The fungal infections were the most often observed pathology (46.7% of examined persons). In mycological tests Candida albicans was most often isolated. Other species: C. kefyr, C. parapsilosis and C. tropicalis were also found. In 4 cases cheilitis angularis was additionally diagnosed. In 16.7% of CsA-treated patients, pathological changes of epithelium with homogenic leucoplakia features were observed. Hypertrophic lesions of oral mucosa in 10% of cases and many small erosions of inflamed mucosa of hard palate in 1 case were also noted. Our observations show connection between incidence of oral mucosa pathologies and immunosuppressive treatment. This suggests that interdisciplinary cooperation is necessary for early start of prevention and treatment program.

Adolescent↗

[Alcohol dependent patients in family doctor's practice in Gdańsk].

Polish family doctors have been given legal rights to diagnose and treat patients with alcohol dependency. Unfortunately, majority of general practitioners do not have proper knowledge and motivation required for this kind of treatment. The aim of the study was to evaluate the preparedness of family doctors in Gdańsk to diagnose and treat patients with alcohol dependency. Fifty family doctors from Gdańsk were included in the study. Forty five agreed to answer the anonymous questionnaire. Forty two out of 45 family doctors did not know the basic notions connected with diagnosis and therapy of alcohol dependency. The screening tests, helpful in the diagnosis of alcohol dependency, were not used by general practitioners--42 of them (almost 94%) did not treat alcohol abusers pharmacologically, and 18 (aprox. 40%) did not have time for such patients. It seems that there is an urgent need to provide further education for general practitioners and make better use of the existing structures engaged in the diagnosis and therapy of alcohol abusers.

Adult↗

[Preparedness of Pomeranian Region hospitals for a possible attack with chemical weapons].

UNLABELLED: The aim of this study was to find out whether the medical staff in the emergency units in all Pomeranian Region hospitals were prepared for possible chemical weapon attack. Key medical personnel, senior doctors and nurses, in 24 hospitals were interviewed by the authors. None of the medical staff have received training in self-protection and management of mass casualties after accidental or terroristic chemical release. There were only four hospitals which had adequate space and special chambers for decontamination. None of the emergency units had special equipment needed for self-protection. The majority of the staff did not know their tasks and individual roles in the case of chemical contamination. None of the personnel had information about antidotes and place of their storage. Only 16.7% of the staff knew the source of quick information about specific treatment of casualties. CONCLUSIONS: The emergency departments in Pomeranian Region hospitals are not prepared for a possible terroristic chemical attack. There is an urgent need for training the medical staff in self-protection and management of mass casualties after accidental or terroristic chemical release. It is important to make bank of antidotes which could be placed in the regional poison control centres. All these procedures could be carried out without too much expenditure.

Chemical Warfare↗

[Neuroleptic malignant syndrome].

Neuroleptic malignant syndrome (NMS) is the most dangerous side effect of phenothiazines therapy. In the period of time from 1995 to 2002 in the Intensive Toxicological Unit there were five patients, 3 men and 2 women, aged from 25 to 62 (average 44.2) years-old, admitted from the regional inpatients psychiatric units with the diagnosis of pneumonia and/or sepsis. The patients about 48-72 hours before admittance were given some phenotiazine derivatives (promazine, perphenazine, clozapine, pipamperon) and/or buthyrophenone (haloperidol) because of psychotic state. Altered consciousness, muscle rigidity, hyperpyrexia (39.0-41.0 degrees C), sweating, tachycardia (120-150/min.), tachypnoea (respiratory rate more than 25/min.) and high level of creatine kinase activity (23,751-112,288 U/l) dominated. Only one patient had clinical picture of pneumonia. Because of the rapid development of acute respiratory failure, respirathorotherapy was initiated and continued for 8 and 10 days in two patients respectively. Transient thrombocytopenia (26,000/microliter) in one subject was observed. The neuroleptic drug was withdrawn and intensive supportive care with administration of bromocriptine (15-20 mg/24 h) was provided. None one of the doctors told the patients about the possibility of NMS during phenothiazines therapy.

Adult↗

[Renal replacement therapy in the elderly patients in the Gdansk Pomeranian region].

Aging of population is a common phenomenon all over the civilized world. It results in increasing number of aged patients with end-stage renal disease. We analysed patients over 65 years who have been qualified for renal replacement therapy (RRT) since 1997. From that time age was no longer barrier for RRT in Pomerania region. Number of aged patients starting RRT raised systematically and achieved 61 pts in 2000. It was 25% of all starting this therapy in our region. In this period we observed changes in the causes of primary renal diseases: diabetic nephropathy raised from 15 to 27.8%, but hypertensive nephropathy unexpectedly was stable at 5%. Most of elderly patients qualified for RRT lived in town--74.6%. It means that many of them living in rural areas did not have adequate nephrological care and probably some of them have not been qualified for RRT. Late referral in this group is still a great problem. Many patients have never been referred to nephrologist before starting RRT. In majority of those cases no definitive diagnosis of ESRD was established. At present we are aiming at international standards and patients are started on RRT with lower level of serum creatinine than earlier. Increasing number of patients with diabetic nephropathy and in advanced age will require great effort both from nephrological community and health care system.

Aged↗