Retinol and alpha-tocopherol in hemodialysis patients.

The biological effects of reactive oxygen species and other radicals controlled by antioxidant mechanisms are modified by various enzymes and other substrates. Antioxidant substrates are divided into those with lipophilic and hydrophilic groups. Retinol and tocopherol are the main representations of lipophilic antioxidants. The aim of the present study was to describe the changes of retinol and alpha-tocopherol which occurred in hemodialysis (HD) patients in respect to the influence of antioxidant systems. The experimental group consisted of 14 patients on regular HD treatment. The control group consisted of 14 healthy blood donors. HPLC was used to measure retinol and alpha-tocopherol in serum. We found that the retinol concentration was significantly higher in HD patients compared to controls (2.35 +/- 0.95 versus 0.90 +/- 0.23 mg/L, p < 0.0001). The concentration of alpha-tocopherol in serum was not different in both study groups (7.32 +/- 3.01 versus. 8.94 +/- 3.57 mg/L). A review of the MEDLINE database since 1985 found a few references concerning these important antioxidant vitamins in HD patients and these contained contrasting results. It has been suggested that some of the complications related to HD including cardiovascular complications, anemia and atherosclerosis may be due to ineffective antioxidant systems and/or to increased free oxygen radical production. The question about supplementation of antioxidants in HD patients is open although there are some positive data regarding the use of moderate and safe selenium supplementation in HD patients. HD patients treated by erythropoietin had increased plasma concentration of retinol and normal level of alpha-tocopherol compared to healthy group. However, this positive finding did not affect lipid peroxidation, which is increased in HD patients and leads to some complications during HD treatment.

Trace elements in hemodialysis and continuous ambulatory peritoneal dialysis patients.

Alterations in blood and tissue concentrations of trace elements in patients with chronic renal failure have been extensively investigated. Selenium, zinc and copper are elements which play an important role in biological systems as components of proteins, enzymes and antioxidants. The concentrations of selenium, zinc and copper were determined in the plasma, erythrocytes and whole blood of patients on regular hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) treatment using the method of inductively coupled plasma mass spectrometry (ICP-MS). Analysis of isotopes 77Se, 66Zn and 65Cu was performed. Methodology presents the major limitation to valid studies on trace element levels in biological materials. One of the widely used contemporary techniques is ICP-MS. It is the most sensitive one and has a high dynamic range. The selenium concentration in the studied compartments (plasma 46.1 +/- 3.0 vs. 78.0 +/- 3.4 microgram/l, p < 0.001; erythrocytes 90.4 +/- 6.5 vs. 134.2 +/- 7.6 microgram/l, p < 0.01; whole blood 67.3 +/- 3.1 vs. 106.4 +/- 3.4 microgram/l, p < 0.001) was significantly lower in HD patients compared to healthy controls. The same result was observed in plasma (63.2 +/- 5.8 vs. 78.0 +/- 3.4 microgram/l, p < 0.05) and whole blood (82.7 +/- 7.4 vs. 106.4 +/- 3.4 microgram/l, p < 0.01) from CAPD patients, but the selenium level of erythrocytes in CAPD patients was the same as in the control group (126.0 +/- 8.8 vs. 134. 2 +/- 7.6 microgram/l). The cooper content of erythrocytes was lower in HD patients than in controls (0.55 +/- 0.02 vs. 0.66 +/- 0.01 mg/l, p < 0.01) and CAPD groups (0.55 +/- 0.02 vs. 0.68 +/- 0.02 mg/l, p < 0.001). There were no differences in copper content in plasma (HD 1. 02 +/- 0.06; CAPD 1.11 +/- 0.09; controls 1.02 +/- 0.05 mg/l) and whole blood (HD 0.87 +/- 0.04; CAPD 0.90 +/- 0.05; controls 0.85 +/- 0.02 mg/l) in HD and CAPD patients and healthy controls. The zinc concentration was increased in the whole blood of CAPD patients (6. 68 +/- 0.36 vs. 5.52 +/- 0.11 mg/l, p < 0.001) and erythrocytes of HD (12.30 +/- 0.23 vs. 10.11 +/- 0.42 mg/l, p < 0.001), and CAPD groups (13.71 +/- 0.56 vs. 10.11 +/- 0.42 mg/l, p < 0.001) compared to controls. However, the plasma zinc concentration was lower in HD patients compared to blood donors (0.69 +/- 0.03 vs. 0.92 +/- 0.03 mg/l, p < 0.001) and CAPD patients (0.69 +/- 0.03 vs. 0.95 +/- 0.04 mg/l, p < 0.001). We did not find a significant increase in trace elements in whole blood after HD. These results suggest differences between plasma, erythrocytes and whole blood concentrations of the studied trace elements. The levels of trace elements are altered by HD and CAPD. A modern precise method with high accuracy, ICP-MS, which was used in our study, eliminated analytical errors and possible interferences.

Lipid peroxidation and antioxidant enzymes in CAPD patients.

The mechanisms of free-radical injury include reactions with proteins, nucleic acids, and polysaccharides; and covalent binding to membrane components and initiation of lipid peroxidation. Cells have developed antioxidant defense to prevent free-radical injury including superoxide dismutase (SOD) and glutathione peroxidase (GPx). Significantly higher concentrations of total malondialdehyde (MDA) in plasma (1.22 +/- 0.42 vs. 0.64 +/- 0.22 micromol/L, p < 0.0001) as well as erythrocytes (2.56 +/- 1.28 vs. 1.03 +/- 0.44 micromol/L, p < 0.0001) of the CAPD patients were found when compared to the control group. The free MDA in plasma and the erythrocytes do not differ significantly in continuous ambulatory peritoneal dialysis (CAPD) patients and the control group. A significantly lower activity of GPx in erythrocytes of CAPD patients (17.85 +/- 2.63 U/g Hb vs. 23.26 +/- 3.61 U/g Hb, p < 0.0001) was found when compared to the control group, but the SOD activity in erythrocytes is not different (2272.36 +/- 579.92 U/g Hb vs. 2347.13 +/- 502.51 U/g Hg, NS). Our results show an increase of total MDA in erythrocytes and plasma. MDA is the product of lipid peroxidation with decreasing activity of GPx, which is capable of detoxifying peroxides. The activity of SOD did not change in CAPD patients. These results propose a possible role of free radicals with reduced antioxidant activity of GPx in CAPD patients and indicate that they could play some role in other pathological conditions such as atherogenesis and hemolysis.

Antioxidant enzymes--superoxide dismutase and glutathione peroxidase--in haemodialyzed patients.

The biological effect of oxygen-reactive species controlled by antioxidant mechanisms are exerted on the basis of antioxidant enzymes and substrates. In this study, the activities of antioxidant enzymes-superoxide dismutase (SOD) and glutathione peroxidase (GPx)-were determined in the erythrocytes of patients on regular haemodialysis treatment. The SOD activity was significantly lower (1,810.38 +/- 609.85 vs. 2,347.13 +/- 502.51 U/g haemoglobin, p < 0.05, or 70.71 +/- 11.50 vs. 100.13 +/- 24.28 mU/10(6) erythrocytes, p < 0.0001), as was the GPx activity (18.80 +/- 4.22 vs. 23.26 +/- 3.61 U/g haemoglobin, p < 0.01), when compared with the control group. A positive correlation between GPx activity and number of haemodialysis sessions was found (p = 0.0038), but no correlation between SOD activity and number of HD sessions. An inpaired antioxidant enzyme defence system, here represented by SOD and GPx levels, can potentiate injury caused by free radicals in haemodialysis patients.

Endothelin in patients with chronic renal failure.

Hypertension, anemia, and arteriovenous shunts represent very important pathogenic factors in the occurrence of cardiovascular morbidity and mortality in patients with chronic renal failure. It can be expected that endothelin (ET), the most potent vasoconstrictor known at present, can react in a significant way to the hemodynamic changes caused by the construction of a vascular shunt or anemia. In 14 patients the plasma ET concentration was examined before and 24 and 7 days after the construction of arteriovenous fistula. In 27 patients undergoing chronic hemodialysis treatment, ET was examined before the erythropoietin (EPO) therapy and after 2 months of EPO therapy, when partial correction of anemia had been achieved. The construction of arteriovenous fistula by itself had no significant influence on the plasma ET concentration. Subcutaneous application of EPO in doses that led to gradual correction of anemia was not accompanied by the rise of plasma ET. The average plasma concentration of ET was significantly higher in hemodialyzed patients, when compared to healthy controls as well as to patients with chronic renal failure before hemodialysis treatment was started.

[Endothelin in patients with chronic kidney failure]. / Endotelin u nemocných s chronickým selháním ledvin.

BACKGROUND: Hypertension, anaemia and arteriovenous shunts represent very important pathogenetic factors in the occurrence of cardiovascular morbidity and mortality in patients with chronic renal failure. It can be expected that endothelin (ET), the most potent vasoconstrictor known at present, can react in a significant way to the haemodynamic changes, caused by the construction of a vascular shunt or anaemia. METHODS AND RESULTS: In 14 patients (7 men and 7 women, mean age 47 years, ranging from 19 to 70 years) the plasma ET concentration was examined before, 24 hours and 7 days after the construction of arteriovenous fistula. In 27 patients (19 men and 8 women, mean age 44 years ranging from 25 to 77 years), undergoing chronic haemodialysis treatment, ET was examined before the erythropoietin (EPO) therapy and after 2 months of EPO therapy, when partial correction of anaemia has been achieved (p < 0.01). CONCLUSIONS: The construction of arteriovenous fistula by itself had no significant influence on the plasma ET concentration. Subcutaneous application of EPO in such doses, which led to gradual correction of anaemia, was not accompanied by the rise of plasma ET. The average plasma concentration of ET was significantly higher in haemodialyzed patients, when compared to healthy controls as well as to patients with chronic renal failure before haemodialysis treatment was started.

The effect of calcium channel blockers on cyclosporine A (Cs A) induced nephrotoxicity in rats.

The limiting factor in the therapeutical use of cyclosporine A (Cs A) is its nephrotoxicity, which may lead to renal failure. Cs A nephrotoxicity may present itself as an acute decrease in GFR, or as a chronic renal injury. Nephrotoxicity is caused by the indirect vasoconstriction effect mainly on proximal tubule and afferent arteriols. In our study we have concentrated on the effect of Ca-channel blockers on Cs A nephrotoxicity. As parameters of toxic kidney damage we have used the urine levels of the following enzymes: N-acetyl-beta-D-glucosaminidase (NAG), gama-glutamyltransferase (GMT) and alkaline phosphatase (ALP). Daily intragastric application of verapamil (V) (dose 1.0 mg/kg BW) or nifedipine (N) (dose 0.1 mg/kg BW) was started in a group of male Wistar rats. Cs A (Sandimun Sandoz, Switzerland) was applied daily intraperitoneally 30 minutes after the application of V or N. The dose of Cs A ranged from 5 mg/kg BW to 25 mg/kg BW in individual groups. The animals were observed for 10 days after the drugs application. Urine samples were collected and examined at the end of the whole experiment. The individual parameters were evaluated in the groups receiving the 3 different doses of Cs A (5-25 mg/kg BW). The serum creatinine rose moderately during the experiment. When the Ca-channel blockers were administered, the rise was not as steep, but when the highest dose of Cs A was administered, the Ca-channel blockers did not influence the elevation of the serum creatinine. Using the standard dose of Cs A (5 mg/kg BW) the protective effect of Ca-channel blockers can be found. In higher doses of Cs A this protective effect was not expressed.

[Ophthalmologic and psychophysiologic changes in patients in long-term dialysis treatment]. / Oftalmologické a psychofyziologické zmeny u pacientu v dlouhodobém dialyzacním lécení.

In 14 patients (7 men and 7 women), mean age 48 and 50 years resp. with chronic renal failure, having regular dialyzation treatment for more than 10 years (2 patients more than 20 years) the authors made ophthalmological and psychophysiological examinations in order to assess complications after prolonged dialysis. In three patients dialysis was discontinued while a graft was functional. In addition to known complications, calcification of the conjunctiva, osmotic cataract and retinal changes and changes of the optic disc the authors detected also changes of the visual field, contrast sensitivity and colour differentiation. They revealed changes of contrast differentiation in all spatial frequencies with a maximum in medium and upper frequencies. They revealed in more than 60% disorders of colour differentiation with a maximum in the blue-yellow and blue area of the spectrum. Ophthalmic complications the frequency of which is declining only rare by endanger the function of the eye.

[Erythropoietin or transfusion?]. / Erytropoetin nebo transfuze?

The cause of anaemia in dialyzed patients is multifactorial. In the submitted paper the authors give an account of their experience with the treatment of 40 patients with erythropoietin (Eprex Cilag Co.). The initial Hb values were 78 +/- 13 g/l and haematocrit 0.24 +/- 0.03. After three months of treatment the haematocrit values were 0.30 +/- 0.02 and the Hb values 103 +/- 7 g/l. After one year's treatment haematocrit values were 0.31 +/- 0.03, Hb 105 +/- 10 g/l. Treatment was started by administration of 150 u/kg/week. Despite considerable individual differences the mean maintenance dose after one-year treatment is only 65 u/kg/week. In two patients treatment was discontinued. Treatment of anaemia in dialyzed patients with erythropoietin is effective and as compared with the risks of repeated transfusions, also economical.

[The carpal tunnel syndrome, its diagnosis and therapy]. / Syndrom karpálního tunelu, jeho diagnostika a lécení.

Secondary amyloidosis is a complication typical for patients on long-term haemodialysis (HD). The first clinical signs are usually shoulder joint pain and CTS. We have questioned 74 patients who were on regular HD treatment and divided them into 3 groups according to the length of HD. Group I--on HD for 1-4 years: there were 35 patients in this group, 15 of them (i.e. 43%) had shoulder joint pain and/or CTS. None of these patients had such symptoms, which would require surgical treatment. Group II--on HD for 5-9 years: there were 22 patients in this group, 15 of them (i.e. 68%) had shoulder joint pain and/or CTS. 3 patients from this group had severe night pain and were therefore indicated for surgical treatment for CTS, each of them on 1 hand only. In 2 cases there was amyloid present in the histological examination. Group III--on HD for over 10 years: there were 17 patients in this group, 13 of them (i.e. 76%) had shoulder joint pain and/or CTS. 5 patients from this group were operated on both hands for severe night pain due to carpal tunnel syndrome. Only 1 patient had positive amyloid on both hands in the histological examination. All the 8 patients (i.e. 13 hands) were examined by EMG before the operation, showing reduction of motor conduction on n. medianus by 30.7 +/- 15.1%. After the operation the EMG control was done in 4 patients (7 hands), showing no improvement in 2 cases and in 5 cases the conduction on the n. medianus was found to be in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipid peroxidation on dialysis membranes.

The aim of this study was to compare the changes of lipid peroxidation during haemodialysis (HD), using various types of dialyser membranes. A significantly higher concentration of total and free TBARS (thiobarbituric acid reacting substance) was found in blood and in plasma of HD patients, compared with the control group of blood donors. During the HD session the TBARS levels grow significantly, compared to the initial levels on both membranes (Alpha 500, Pro500), and are significantly higher after 15 min of HD on Alpha 500 membrane. The levels of TBARS appear to be significantly higher in patients on regular HD treatment, which may be due to a more intensive lipid peroxidation. There were significant acute changes in lipid peroxidation during one HD session. The changes in lipid peroxidation differ with the use of various HD membranes.

Diagnosis and treatment of carpal tunnel syndrome.

Secondary amyloidosis is a complication typical for patients on long-term hemodialysis. The first clinical signs are usually shoulder joint pain and carpal tunnel syndrome (CTS). We have questioned 74 patients who were on regular hemodialysis (HD) treatment and divided them into 3 groups according to the length of HD. Group 1--on HD for 1-4 years: There were 35 patients in this group, 15 of them (i.e., 43%) had shoulder joint pain and/or CTS. None of these patients had symptoms that would require surgical treatment. Group II--on HD for 5-9 years: There were 22 patients in this group, 15 of them (i.e., 68%) had shoulder joint pain and/or CTS. Three patients from this group had severe night pain and were therefore indicated for surgical treatment for CTS, each of them on 1 hand only. In 2 cases amyloid was present in the histological examination. Group III--on HD for over 10 years: There were 17 patients in this group, 13 of them (i.e., 76%) had shoulder joint pain and/or CTS. Five patients from this group were operated on both hands for severe night pain due to carpal tunnel syndrome. Only 1 patient had positive amyloid on both hands in the histological examination. All the 8 patients (i.e., 13 hands) were examined by EMG before the operation, showing reduction of motor conduction on n. medianus by 30.7 +/- 15.1%. After the operation the EMG control was done in 4 patients (7 hands), showing no improvement in 2 cases and in 5 cases the conduction on the n. medianus was found to be in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

[Significance of tumor size in the outcome of radiation treatment of cancer at various sites]. / Znacheniia ob"em opukholi v iskhode luchevogo lecheniia raka raznykh lokalizatsii.

The authors have established probable importance of tumor lesion sizes in the outcome of radiotherapy choosing by way of example 2 cancer sites (the larynx and cervix uteri). If the rate (%) of probable tumor spreading within a certain stage is the same for both cancer sites, then the 5-year survival rate for these sites is similar (or the same). If a tumor within a certain stage is equal to one third of its probable maximum spreading, the 5-year survival rate is approximately 85%; if it is equal to 1/2, the 5-year survival rate is approximately 60%; over 1/2--approximately 40-30%. If tumor involvement is complete, therapeutic efficacy is doubtful. It can be assumed that the above correlations established for 2 cancer sites (the larynx and cervix uteri) have general significance and may be applied to all cancer sites.

[Probability of recovery from cancer of the cervix in relation to the stage and volume of the tumor]. / Veroiatnost' izlecheniia raka sheiki matki v zavisimosti ot stadii protsessa i ob'ema opukholi.

The authors proposed a method for calculation of sizes of lesions at different stages (T) of cervical cancer, their correlation and the comparison of 5-year survival rates after combined therapy. The above method based on the sizes of anatomical structures, proved to be very important for analysis of the efficacy of cervical cancer therapy. The above method based on the sizes of anatomical structures, proved to be very important for analysis of the efficacy of cervical cancer therapy. Substaging was clinically substantiated because it reflected some peculiarities in tumor spreading with relation to a tumor size. Tumor sizes could differ significantly within the same stage and coincide at different stages entailing a possible difference in therapeutic results. The 5-year survival rate of cervical cancer patients with a lesion size of 1 cm3 was over 80%, and with an increase in tumor sizes over 15 cm3 it was under 50%. When a tumor was 80 cm3 and more in size its cure was highly improbable.

[Effectiveness of repeated radiotherapy in patients with laryngeal cancer]. / Effektivnost' povtornogo luchevogo lecheniia bol'nykh rakom gortani.

The authors present the results of repeated radiotherapy of 86 patients with laryngeal cancer; of them 64 (74.4%) had local recurrences, 13 (15.2%) extended tumor growth and 9 (10.4%) metastases to the neck lymph nodes. Immediate cure was achieved in 36 (42%) patients, the volume of involvement not exceeding 1 cm3 irrespective of the site of a recurrence in the larynx. Long-term results were followed up in 74 patients after repeated irradiation. Thirty-seven patients have been alive from 1 to 13 years, disease extension was noted in 13, 19 patients were operated upon, and 5 died of laryngeal cancer. Late radiation complications were revealed in 13 (17.5%) patients. Basing on the previous results (V. V. Kholin, 1979, 1981) one can conclude that in order to avoid radiation complications the summary focal dose in repeated irradiation should not exceed in an equivalent value the optimum single therapeutic dose of 24 Gy with reference to 1 cm3 of the involvement volume.