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Objectives: It has been clearly demonstrated that after donor-specific cell transfer the prolongation of allograft survival can be obtained, but the problem of how to inoculate cells remains unresolved. In this study, the effect of either portal venous (PV) or systemic intravenous (i.v.) inoculations of rat donor-specific spleen cells on subsequent renal graft survival was evaluated., Methods: LEW recipients received 10(6) of spleen cells from allogeneic Fischer or syngeneic donors 30 days before kidney transplantation by either PV or i.v. routes. Animals from the control group obtained buffered saline by the same routes., Results: Fischer grafts in nonimmunized LEW recipients were rejected after 9.6 +/- 1.3 days. In contrast, the immunization of the recipients by the pretreatment with donor spleen cells prolonged renal allograft survival significantly (p < 0.002). However, no difference in the graft survival was observed between animals inoculated with cells either by PV or by i.v. routes. In each studied group, long-time graft survival (> 100 days) was achieved in one case., Conclusions: These observations suggest that the effect of the various routes of allogeneic cell inoculations on subsequent organ graft survival time depends on the interval between the cell transfer and organ transplantation. Intravenous route seems to be as effective as PV route when transplantation is performed several days after donor-specific cell transfusion.

Left ventricular hypertrophy (LVH) is common and important predictor of risk of death in end-stage renal failure. In the present study we have analysed the relationship between 24-h ambulatory blood pressure (BP) profile and LVH. The effect of parathyroid hormone (PTH) on was also assessed. From a cohort of 85 patients with crf we selected for analysis 59 stable patients. Ambulatory BP 24-h monitoring, echocardiography (ECHO), body mass index (BMI), serum creatinine, hemoglobin, total protein, albumin, electrolytes and PTH concentrations were assessed in all patients. Concentric LVH was detected by ECHO in 46 patients, in 13 patients excentric LVH was observed. Mean 24-h ambulatory sBP, dBP, mean 24-h ambulatory day sBP, dBP as well as night sBP and dBP were significantly higher than in a control group 60 healthy subjects. It was a correlation between mean 24-h ambulatory sBP and left ventricular mas (LVM) r = 0.606 (p < 0.0001), between mean dBP and (LVM) r = 0.498 (p < 0.001), between mean day sBP and (LVM) r = 0.591 (p < 0.0001), between mean day dBP and (LVM) r = 0.479 (p < 0.001), between mean night dBP and (LVM) r = 0.548 (p < 0.0001), between left ventricular mass index (LVMI) and mean sBP r = 0.428 (p < 0.05), between LVMI and mean day sBP r = 0.442 (p < 0.05). The loss in physiological night-time BP was observed in all patients. It was also correlations between PTH and (LVM) r = 0.704 (p < 0.001), and between BMI and LVMI r = -0.451 (p < 0.05). LVH is common in crf patients. These results confirmed that strong correlations between BP values and LVH and between serum PTH concentrations and LVH indicate that both hypertension and hyperparathyroidism play an important role in the LVH development.

Background: Previous studies have suggested that alpha-adducin (alpha-ADD) polymorphism may identify patients with a salt-sensitive form of hypertension., Aim: To investigate the association between Gly460Trp polymorphism of alpha-ADD and the pattern of blood pressure response to subacute (1 week) salt loading and depletion in young adult thin Polish hypertensives., Methods: The study group consisted of 44 subjects with salt-sensitive hypertension (SS) and 24 subjects with non-salt-sensitive hypertension (SR). Genomic DNA isolated from peripheral blood leukocytes was amplified by PCR method with primers flanking the polymorphic region. The mismatch near to 3'-end of the upstream primer was introduced to create a Nla III restriction site in Trp 460 allele. In addition, excreted fraction of filtered sodium (FENa), plasma renin activity (PRA) and plasma concentrations of aldosterone (ALDO) were determined on normal, low and high salt diets., Results: FENa on normal or high salt diets were significantly lower in the SS hypertensives as compared with the SR patients. PRA in SS group was also significantly lower as compared with results in SR group, but only on high salt diet. No significant difference was detected in frequencies of genotypes and alleles of alpha-ADD gene between SS and SR subjects. An additional analysis with regard to genotype (Gly/Gly vs. Gly/Trp+Trp/Trp) showed no significant difference in changes of blood pressure as well as in results of laboratory investigations., Conclusion: Our results suggest lack of association between Gly460Trp polymorphism of alpha-adducin gene and salt sensitivity of blood pressure in Polish hypertensives., (Copyright 2001 S. Karger AG, Basel)

The introduction of new immunosuppressive regimens results in the significant improvement in the outcome of patients after kidney transplantation. However, about 5 percent of renal transplants are lost every year. Not only immunological (alloantigendependent) but also nonimmunological (alloantigen-independent) factors are involved in late graft loss. Among them, hypertension, hyperlipidemia, proteinuria, genetic predisposition, viral infection and nephrotoxicity of immunosuppressive drugs contribute to the development and to the progression of chronic post-transplant nephropathy. Hypertension can be both the cause and the consequence of chronic allograft failure. Hypertension is frequently observed before transplantation, persists after grafting and increases the risk of chronic allograft nephropathy. Hypercholesterolemia, obesity, atheromatosis, polycythemia, and excessive salt intake are factors contributing in post-transplant hypertension. However, in some cases, hypertension can be transferred with the grafted kidney, as observed in normotensive patients before renal transplantation. In 1 to 12 percent of cases, the cause of post transplant hypertension is the stenosis of the transplant artery. Sometimes the presence of hypertension in renal recipients may result from the recurrence of glomerulonephritis or from the development of glomerulonephritis de novo in the graft. Also immunosuppressive treatment with corticosteroids and cyclosporine A contributes to the increased prevalence of hypertension by 20-30 percent. The development of the graft nephroarteriolosclerosis as a consequence of hypertension accelerates the progression of the post-transplant nephropathy. Adequate control of the arterial pressure (< 140/90) should be achieved in all renal transplant recipients. Reduction in protein and salt intake is important to reduce hyper-filtration and slows the progression of transplant nephropathy. However, pharmacological treatment is usually needed. Angiotensin-converting-enzyme inhibitors, angiotensin II type I receptor antagonists exhibit beneficial hemodynamic effect leading to the reduction of glomerular hypertension and proteinuria. Calcium antagonists besides their systemic antihypertensive effect, can protect renal grafts from vascular and renal toxicity of CyA. Sometimes, combined therapy with these and other antihypertensive drugs and diuretics is necessary.

Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis of the respiratory tract and glomerulonephritis (GN). Prognosis of this disease is poor and about 20% of untreated patients die after one year from the onset. WG was recognized in 45-year-old patient on the basis of: 1) clinical symptoms (joint pain and swollen, purpura on the skin which appeared one week after respiratory tract infection, ulceration of the tonsils and lingula), 2) results of additional testing (X-chest-ray-infiltrates of both lungs), positive results of the cANCA (titre 1:640) and rapidly progressive renal failure [the increase of serum creatinine level (Pcr) from 123.7 to 707 mumol/l (1.4 to 8.0 mg/dl) during one week]. Renal biopsy revealed extracapillary GN (cellular crescents in 7 out of 8 glomeruli and scattered foci of fibrinoid necrosis of capillary walls in all). At the beginning of the treatment Pcr raised to 884 mumol/l (10 mg/dl) and the patient required hemodialysis. He was treated with methylprednisolone (M) at flash doses of 1000 mg/24 h by three days followed by 125 mg/24 h i.v.--because of peptic ulcer, with cyclophosphamide (C-150 mg/24 h p.p.), with trimetoprim/sulphametoxazole, with pentoxifylline and omeprazol. After six weeks of the treatment in the control kidney biopsy sclerotic changes in 10 out of 13 glomeruli and diffuse interstitial fibrosis were found. However, during the same time, we observed clinical remission of the disease and the decrease of Pcr to 176.8 mumol/l (2 mg/dl). The M dosis was reduced by 5 mg every weeks and the C dosis--to 50 mg (because of the increase of aminotransferase levels) After six months of the treatment Pcr was 132.6 mumol/l (1.5 mg/dl) and CANCA titer was 1:16. In this case of RPGN, despite off the progression of the morphological changes in the kidney, we obtained the clinical remission of the disease and significant decrease of Pcr level. These results suggest that aggressive treatment of WG is justified even in patients with advanced renal failure requiring dialysis and in such patients clinical remission is possible to occur.

Focal segmental glomerulosclerosis (FSGS) is a glomerular disease of varying severity. Most patients, however, develop end-stage renal failure within 10 years from clinical onset. In this retrospective study, the outcome of immunosuppressive treatment in 22 adult patients with biopsy-proven primary FSGS was evaluated. Eleven patients were treated with prednisone, azathioprine and chlorambucil (group A) and 11 with prednisone and pulse cyclophosphamide (group B). The nephrotic syndrome (NS) was found in 4 patients from the group A and in 3 patients from the group B, arterial hypertension in 8 and 9 patients, respectively. During the follow-up lasting about 50 months as the mean, 70% of the patients did not respond to the treatment and complete remission was obtained only in 3 patients from the group B. On the other hand, 7 patients progressed into CFR. Among them, 5 out of 7 patients with NS (4 from the group A) needed dialysis treatment or doubled their Pcr after a mean of 38 months. This study confirms poor outcome of immunosuppressive treatment in patients with FSGS. However, of the two forms of treatment used in the study, the response appeared to be better and more lasting with cyclophosphamide than with azathioprine and chlorambucil. Corticosteroids associated with pulse cyclophosphamide therapy seems to improve the chances of remission and to protect from renal dysfunction.

Low serum concentration of the carnitine is one of the causes of muscle weakness and cardiomyopathy in patients with chronic renal failure treated by hemodialysis. The carnitine facilitate transport of the free fatty acid into the straitened muscle cells where the product of oxidation is energy-ATP. In the present paper we presented the investigation of the influence of L-carnitine substitution on cardiac performance. The results indicate the positive influence of this treatment on metabolic and haemodynamic cardiac parameters. The subjective patients opinion of L-carnitine treatment was also positive.

We describe three cases of patients with systemic lupus erythematosus in which additional infections: mycotic, bacterial and viral deteriorated renal function and patients needed the dialysis treatment. The patients with autoimmunologic disorders are very sensitive for different infections which need rapid diagnosis and intensive treatment.

The renin-angiotensin-aldosterone system plays an important role in blood pressure regulation by influencing salt-water homeostasis and vascular tone. The purpose of the present study was to search for associations of single nucleotide polymorphisms on 3 major candidate genes of this system with the plasma concentrations of the corresponding renin-angiotensin-aldosterone system components considered as quantitative phenotypes. Genotyping was performed in 114 normotensive subjects for different variants of the angiotensinogen (AGT) gene (C-532T, G-6A, M235T), the angiotensin I-converting enzyme (ACE) gene [4656(CT)(2/3)], the aldosterone synthase (CYP11B2), and the type 1 angiotensin II receptor (AT1R) gene (A1166C) by hybridization with allele-specific oligonucleotides (ASO) or enzymatic digestion of polymerase chain reaction products. Plasma levels of AGT, ACE, angiotensin II (Ang II), aldosterone, and immunoreactive active renin were measured according to standard techniques. Platelet binding sites for Ang II were analyzed by the binding of radioiodinated Ang II to purified platelets. B(max) and K(D) values of the Ang II binding sites on platelets of each individual were calculated to examine a possible relationship between these parameters and the AT1R genotype. A highly significant association of the ACE 4656(CT)(2/3) variant with plasma ACE levels was observed (P<0.0001). ANOVA showed a significant effect of the AGT C-532T polymorphism on AGT plasma levels (P=0.017), but no significant effect was detectable with the other AGT polymorphisms tested, such as the G-6A or the M235T. A significant effect association was also found between the C-344T polymorphism of the CYP11B2 gene and plasma aldosterone levels, with the T allele associated with higher levels (P=0.02). No genotype effect of the AT1R A1166C polymorphism was detected either on the B(max) or the K(D) value of the Ang II receptors on platelets.

This paper summarizes current, but controversial opinions of different authors evaluating the effect of Bsml polymorphism of the vitamin D receptor gene on the parathyroid function, calcium absorption from the digestive tract and bone mineral density (BMD) in persons with normal renal function and in patients with chronic renal failure. On the basis of these data, the recapitulation of the prevailing opinions was undertaken. Contemporary it is admitted, that the persons with bb genotype and normal renal function are at risk for the development of the parathyroid adenomas while in the patients with chronic renal failure the bb genotype may favour parathyroids hyperplasia. It is also believed that bb genotype in the persons with normal renal function facilitates calcium absorption and is associated with greater BMD. Few investigations performed in the patients with chronic renal failure suggest that the BB genotype may partially influence lower BMD in the subgroup of younger patients treated with hemodialysis for a relatively short period. Existing controversies need however further clarification.

Because mesangial cells (MC) are a target and a degradation site for angiotensin II (ANG II), we characterized the degrading enzymes and receptors of ANG IV, a metabolite of ANG II, on these cells. ANG IV was metabolized into its NH2-terminal deleted peptides, ANG II-(4-8), ANG II-(5-8), and ANG II-(6-8) by rat MC. Total protection of ANG IV was obtained only when PC-18, a specific aminopeptidase N (APN) inhibitor, and JFH-27A, a mixed inhibitor of dipeptidylaminopeptidase (DAP) and neutral endopeptidase (NEP), were simultaneously added. In contrast, thiorphan, an NEP inhibitor, was inactive. These results demonstrate the exclusive role of APN and DAP in ANG IV degradation. 125I-labeled ANG IV binding was studied in the presence of PC-18 and JFH-27A to suppress ligand degradation. Under these conditions, ANG IV-specific receptors could be demonstrated with a KD of 1.8 nM and a density of 55 fmol/mg. In contrast with MC, no evidence for ANG IV receptors could be obtained in freshly isolated glomeruli. ANG IV stimulated cytosolic calcium concentration in MC, whereas its NH2-terminal deleted metabolites were inactive. Therefore, ANG IV must be protected from degradation by APN and DAP in studies on the nonimmediate biological effects of this peptide.

Both environmental and genetic factors are implicated in the pathogenesis of essential hypertension. The defect of the ANP precursor gene leading to the decrease of ANP synthesis are a cause of the development of sodium-sensitive hypertension in animals. Recent findings in African-Americans who are a model of sodium-sensitive population, reveal a strong association between Sma I polymorphism at intron 2 (the polymorphic site is identical for Hpa II restriction enzyme) or both Sma I and Sca I polymorphism at exon 3 of ANP precursor gene and essential hypertension. The aim of our study was to optimize the methods for Sma I and Sca I analysis in the ANP precursor gene (PCR followed by digestion with restriction enzymes) and to determine the frequencies of Sma I or Sca I genotypes and alleles in patients with sodium-sensitive (SS) or sodium-nonsensitive (SR) hypertension. The Sma I heterozygous mutation (WM genotype) were detected in 4 (8.9%) SS patients and in 2 (10%) patients in SR group. The frequency of Sca I M allele (allele with mutation) was significantly higher in SS group as compared to sodium-nonsensitive hypertensives. Our results suggest that, in contrast to Black hypertensives, in Caucasians with essential hypertension the Sma I polymorphism is very rare and the Sca I polymorphism of ANP precursor gene is associated with sodium-sensitivity of blood pressure.

Atrial natriuretic peptide (ANP) is involved in the pathogenesis of sodium-sensitive hypertension. The loss of Sca I restriction site in the ANP precursor gene abolishes the regular stop codon. The aim of our study was the analysis of the Sca I gene polymorphism in 23 patients with sodium-sensitive hypertension, the molecular characteristic of the mutation and the comparison of the blood pressure values, plasma renin activity, plasma ANP and aldosterone concentration between patients with or without mutation. Applying the polymerase chain reaction (PCR), followed by digestion with Sca I, the heterozygous mutation has been found in 9 (39%) patients. The sequencing of PCR products indicated that the loss of Sca I restriction site is caused by T2238-->C transition leading to the translation of ANP with two additional arginines. The higher concentration of ANP in plasma has been found in T2238-->C transition patients on normal and high sodium diet as compared with patients without mutation. These preliminary results suggest that the heterogeneity of sodium-sensitive hypertension is associated with the T2238-->C mutation of the ANP precursor gene.

The aim of study was to evaluate bone mineral density (BMD) in lumbar spine (AP Spine), total body (Total Body) and distal site of radius (Forearm), and selected markers of bone formation: serum alkaline phosphatase (ALP) and osteocalcin(OC), and bone resorption: pyridinoline (PIR) and deoxy-pyridinoline (DPIR) in urine, in patients with long-standing insulin-dependent diabetes mellitus (IDDM), in comparison to healthy controls. Additionally, the influence of age, sex, smoking, duration of IDDM, the degree of metabolic control, or coexisting chronic complications of diabetes (retinopathy, incipient nephropathy, polyneuropathy) on the studied indices of bone metabolism in patients with IDDM were evaluated. The study was carried on 54 diabetic patients (23 F, 31 M) and 25 healthy individuals (13 F, 12 M). BMD was measured by DEXA (LUNAR DPX-L System). ALP was assessed by enzymatic method, and OC by RIA (Incstar Corporation). PIR and DPIR were assessed by EIA (Metra Biosystems). It was found that patients with long-standing IDDM have significantly lower BMD than healthy controls. The incidence rate of osteopenia and osteoporosis is significantly higher in this group of patients in comparison to the controls. In comparison to healthy subjects, patients with IDDM have significantly higher, but within normal reference range, serum ALP and OC, accompanied by similar PIR and not significantly increased DPIR. Duration and metabolic control of diabetes, or the coexistence of its chronic complications do not correlate with BMD or the studied indicies of bone turnover.

Because angiotensin II (Ang II) has been found at high concentrations in the proximal tubule fluid and because tubular brush border membranes exhibit a marked capacity for degrading Ang II, we thought it of interest to examine the binding sites for Ang II (3-8) (referred to as Ang IV), a metabolite of Ang II, downstream in the nephron. We studied the binding of [125I]-Ang IV and also of [125I]-Sar1, Ala8, Ang II to SV-40 transformed human collecting duct cell (HCD) membranes. No specific binding site for [125I]-Sar1, Ala8, Ang II and no Ang II-dependent cytosolic calcium response could be observed. Moreover, no signal for the human type I Ang II receptor (hAT1) mRNA was present in HCD cells. In contrast, [125I]-Ang IV bound specifically to HCD cell membranes. Mean Kd and Bmax values derived from saturation binding studies were 5.6 +/- 2.0 nM and 1007.6 +/- 140.2 fmol/mg protein, respectively. The rank order of affinity for competitive Ang II-related peptides was: Ang IV > Ang III > Ang II > Ang II (4-8) > Ang II (1-7). [125I]-Ang IV binding was not modified by nonpeptide AT1 (losartan) or AT2 (PD123177) antagonists. GTP gamma S and dithiotreitol did not affect [125I]-Ang IV binding. Ang IV stimulated cAMP production by intact HCD cells in the presence of forskolin but did not modify cGMP production or cytosolic calcium concentration. Taken together, these results indicate that HCD cells represent a target site for Ang IV but do not possess Ang II receptors.

Unlabelled: The aim of study was an evaluation of bone mineral density (BMD) measured by LUNAR DPX-L System in lumbar spine (AP), total body and distal site of forearm (Forearm) in patients with insulin-dependent diabetes mellitus (IDDM), in relation to duration of the disease, degree of metabolic control and serum osteocalcin (OC). The study was performed on 58 patients with IDDM (26 F, 32 M; mean age: 40.1 +/- 10 yrs, mean duration of IDDM: 17.2 +/- 8 yrs) and 33 healthy, age-matched subjects (18 F, 15 M). Patients with overt nephropathy, concomitant diseases known to affect bone metabolism and women after menopause were excluded from the study. BMD was decreased in patients with IDDM in comparison with the controls: 1.13 +/- 0.1 vs 1.25 +/- 0.15 g/cm2, p < 0.001 in AP, 1.12 +/- 0.07 vs 1.2 +/- 0.07 g/cm2, p < 0.001 in Total body oraz 0.37 +/- 0.05 vs 0.4 +/- 0.05 g/cm2, p < 0.05 in Forearm. The degree of metabolic control of IDDM evaluated by serum HbAlc levels did not influence the values of BMD. Similarly, duration of IDDM did not correlate with BMD. OC level was significantly higher in diabetic patients than in control group: 4.88 +/- 2.2 vs 3.89 +/- 1.2 ng/ml, p < 0.05., Conclusions: 1) In patients with long-standing IDDM, Total Body, AP Spine and Forearm BMD were significantly decreased in comparison with the controls, and the decrease of BMD was higher in men than in women. 2) In patients with IDDM the decrease of BMD did not depend on the degree of metabolic control and duration of the disease. 3) Serum OC determinations may help in the identification of cases with risk of development of diabetic osteopenia.

Plasma prekallikrein (PPK) is a single-chain glycoprotein synthesized in the liver. The aim of our study was to evaluate a plasma prekallikrein as the marker reflecting liver protein synthesis in patients with chronic liver diseases. PPK levels have been measured by own modification of amidolytic micro-assay in 43 patients with chronic liver diseases and 37 healthy volunteers as control group. As compared to control group, PPK level was significantly decreased in patients with chronic active hepatitis and with decompensated liver cirrhosis and significantly increased in patients with liver cirrhosis complicated by hepatocellular carcinoma. There was no difference in plasma prekallikrein between patients with compensated liver cirrhosis and controls. The results suggest that PPK might be a useful index for the assessment of residual functional liver mass in patients with chronic liver diseases.

The purpose of the study was to compare the effect of treatment with an angiotensin converting enzyme inhibitor (Lisinopril, MSD) or calcium blocker (Nifedipine retard, MSD) treatment during three months on blood pressure (measured with sphygmomanometric method and ambulatory blood pressure monitoring--ABPM) and urinary albumin excretion in essential hypertension class I acc. to WHO. Fifteen untreated patients aged 38 +/- 5 years with essential hypertension participated in the study and received diet with normal sodium content. Urinary albumin excretion was measured by RIA method in two 24 hour urine collections and mean value was calculated. ABPM was measured with Spacelabs monitor. After first examination 8 patients were randomly selected for the treatment with lisinopril and 7 patients to the treatment with nifedipine. The doses of both drugs were gradually adjusted to reach diastolic blood pressure below 90 mmHg. After 3 months of treatment urinary albumin excretion and blood pressure was found in both after treatment in patients treated with lisinopril but not in those receiving nifedipine. In patients treated with lisinopril a correlation between the decrease in systolic and diastolic blood pressure (measured by ABPM) and decrease of urinary albumin excretion was demonstrated. It was concluded that the normalization of blood pressure induced by lisinopril treatment in patients with uncomplicated essential hypertension and normoalbuminuria is accompanied with significant diminution of urinary albumin excretion which suggests preventive action of the drug in the development of microalbuminuria. Diminution of urinary albumin excretion caused by lisinopril is probably due to both the decrease of blood pressure and the specific renal action of the drug.

The aim of the study was to evaluate plasma concentration of fibrinogen, plasma activity of antithrombin III (AT-III) and plasma activity of plasminogen activator inhibitor (PAI-I) in insulin-dependent diabetic (IDDM) patients and the assessment of correlation between them and the parameters of glyco-metabolic control comprising glycemia and concentrations of fructosamine and glycated hemoglobin HbA1c. Eighteen IDDM patients (mean age 28.3 +/- 11.3 ys, mean duration of disease 12.2 +/- 5.3 ys) without over nephropathy and without macroangiopathy were investigated. Control group consisted of 8 healthy subjects. Plasma fibrinogen concentrations were similar in IDDM patients and in controls (3.54 +/- 0.45 g/l and 3.31 +/- 0.54 g/l respectively). Plasma activity of AT-III in diabetic patients (90.6 +/- 22.4%) was similar to that in healthy subjects (94.6 +/- 25.0%). Fibrinogen concentrations and AT-III activities showed no correlation with glycemia and concentrations of fructosamine and HbA1c. Plasma activity of PAI-I was significantly lower in diabetics than in controls (respectively 1.56 +/- 0.72 U/ml and 2.75 +/- 1.25 U/ml, p < 0.005). PAI-I activity correlated negatively with fasting blood glucose (p < 0.05) but did not correlate with concentrations of fructosamine or HbA1c. The results suggest that glycemic control in diabetic patients do not influence on concentrations of fibrinogen and activity of AT-III but diminished activity of PAI-I is related to hyperglycemia.

The aim of the study was the comparison of the effect of seven day treatment with nifedipine (2 x 10 mg daily) and subsequently with verapamil (3 x 40 mg daily) on blood pressure, heart rate, plasma ANP, cGMP, renin activity (PRA), aldosterone (ALDO) concentrations in patients with primary hypertension. The material consisted of 12 untreated patients with primary arterial hypertension Io WHO. These results suggest that short-term treatment with nifedipine and subsequently with verapamil in patients with primary hypertension Io WHO not influence on plasma ANP, cGMP, PRA and ALDO in spite of blood pressure reduction and the changes in heart rate. It seems that ANP did not participate in hypotensive action of nifedipine and verapamil. No augmentation of urinary sodium excretion was found after short-term treatment with nifedipine or verapamil.

The effect was studied of blood pressure lowering treatment on renal failure and albuminuria (UAE) in patients with type I diabetes (IDDM) and imminent nephropathy as well as in patients with over diabetic nephropathy. The group of 24 patients with imminent nephropathy was subdivided: 1. twelve patients with borderline or overt hypertension with mean BP lowered not below 100 mmHg, and 2. twelve patients with BP within the normal limits, taking no hypotensive agents. In the other group of 12 patients with overt diabetic nephropathy hypertension was lowered below 105 mmHg and kept so for at least two years. All patients estimated their glycemia and glycosuria by themselves, ate 0.8 g protein/kg/24 h and about 100 mmol Na/24h. Under hospital conditions the following were estimated: albuminuria, glomerular filtration rate (51Cr EDTA) and effective renal blood flow (131I hippurate). The same examinations were repeated 1 year and 2 years later. The lowering of BP below 100 mmHg in patients with imminent diabetic nephropathy significantly lowered microalbuminuria without changing GFR, ERPF despite good or satisfactory compensation of diabetes. Maintaining BP below 105 mmHg for 2 years did not prevent the patients with overt nephropathy to develop progressive renal failure despite the rate of GFR deterioration and of the increase of albuminuria slowed down.

The prevalence of osteoporosis and risk factors were evaluated in the random sample of Szczecin population aged over 50 years. Five hundred five individuals (273 women and 232 men) were examined. Risk factors for osteoporosis were evaluated with the aid of an questionnaire. Two X-ray pictures of both thoracic and lumbar spine were taken in the lateral position in all examined subjects and evaluated for osteoporosis. The most frequently encountered risk factors included: low physical activity (60% of women and 50% of men), tobacco smoking (43% of women and 79% of men), low consumption of the diary products in adolescence (53% of women and 49% of men), history of bone fractures, early menopause, and diabetes mellitus. The interpretation of X-ray findings showed that the incidence of osteoporosis was increasing with the age in both sexes, and was considerably higher in women. An analysis of the relationship between risk factors and radiological diagnosis of osteoporosis with chi 2 test showed that significantly higher incidence of the disease in women was associated with long-term immobilization, low milk consumption, tobacco smoking, and early menopause. Osteoporosis in men correlated with only tobacco smoking.

The aim of study was evaluation of fructosamine test in monitoring of diabetes mellitus complicated by proteinuria. Twenty patients with type 1 diabetes mellitus without proteinuria and 20 diabetic (type 1) patients with proteinuria were examined. Absent-present proteinuria was alone differential parameter between these groups. Correlations between past-glycaemia and other indices of diabetes balance as fructosamine, glycated haemoglobin and fructosamine: albumin molal ratio were examined. Results of study suggest that fructosamine test is useless in monitoring diabetes with proteinuria, but fructosamine: albumin molal ratio is a good parameter in monitoring of either: diabetes mellitus without proteinuria and with proteinuria.

The results of different methods of treatment of infiltrative endocrine ophthalmopathy in 68 patients (52 women and 16 men) aged 28-63 years were evaluated. The analysis of the results indicates that combined treatment with glucocorticoids and tele-cobalt therapy may be considered as the method of choice. In patients with rapidly progressive ophthalmopathy and in patients with inactive peptic ulcer intravenous pulsed glucocorticoid administration may be used instead of oral treatment. When contraindications to corticotherapy exist, good results of treatment may be achieved with tele-cobalt therapy alone. Plasmapheresis seems less effective but may be used in rapidly progressive, short term lasting ophthalmopathy in patients refusing tele-cobalt therapy, in connection with glucocorticoids or after unsuccessful glucocorticoid therapy alone. The consecutive treatment with glucocorticoids and tele-cobalt therapy is effective but requires much more time.

The aim of the study was an evaluation of the effect of different dietary sodium intake on: blood pressure, plasma concentration of atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), aldosterone (ALDO) and plasma renin activity (PRA) in patients with primary sodium sensitive arterial hypertension class I acc. to WHO criteria. Thirteen patients, non treated, with sodium sensitive arterial hypertension aged 30 +/- 8 years participated in the study. Blood samples were taken three times: in 5th day of normal sodium intake (100-120 mmol Na per 24 h); in 5th day of low sodium diet (10-20 mmol Na per 24 h); in 5th day of high sodium diet (200-220 mmol Na per 24 h). During 24 hours before each blood sampling the urine was collected and sodium and potassium excretions were evaluated. Concentrations of ANP, cGMP, ALDO in plasma and PRA were determined by radioimmunoassays and serum sodium and potassium concentration by flame photometry. Significant (p < 0.05) diminution of blood pressure, plasma ANP and cGMP concentrations and the increase of plasma ALDO and PRA after sodium restriction when compared to normal sodium diet were found. High sodium diet resulted in significant increase of blood pressure, plasma ANP and cGMP concentrations to the values comparable with these on normal sodium diet. On the contrary PRA and plasma ALDO concentration decreased (p < 0.001) below the values during normal sodium diet. Urinary sodium excretion corresponded to dietary sodium intake during all diets.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this work was an evaluation of the effect of the acute hypervolemia induced by 90 min intravenous infusion of 1500 ml 0.9% NaCl (16.7 ml/min) on blood pressure, plasma concentration of the atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), aldosterone (ALDO), plasma renin activity (PRA) in patients with essential hypertension on the normal, low and high sodium intake. Twelve patients with noncomplicated essential sodium-sensitive arterial hypertension participated in the study. Sodium chloride infusions were performed three times: first--on the fifth day of normal daily sodium u intake (110-120 mmol/day), second--on the fifth day of low sodium intake (10-20 mmol/day), third--on the fifth day of high sodium intake (200-220 mmol/day). Acute intravenous sodium chloride load induced a significant increase of the mean arterial pressure (MBP) only when the patients were on the high sodium diet. This increase of the MBP was associated with a significantly lower increment of plasma ANP, cGMP, lower decrement of ALDO and PRA when compared to normal- or low- sodium intake. The results suggest an impairment of the adaptive homeostatic mechanisms induced by an acute intravenous sodium load in patients with noncomplicated salt-sensitive essential hypertension ingesting high-sodium diet.

The aim of the study was to answer the question whether a rapid decrease in serum triiodothyronine (T3) and thyroxine (T4) levels resulting from the treatment with a full dose (3 x 20 mg daily) of methimazole applied in patients with thyrotoxicosis is associated with the parallel diminution of plasma atrial natriuretic peptide (ANP) and its second messenger-cyclic guanosine monophosphate (cGMP) concentrations. Sixteen patients with thyrotoxicosis of mean age 41.5 +/- 10.5 years participated in the study. Short-term (10 days) methimazole treatment resulted in a significant decrease in serum T3 and T4 concentrations to the values found in 14 healthy subjects serving as control group. Plasma ANP and cGMP levels also decreased significantly during the treatment attaining the normal range. A significant correlation was found between the decrease in serum T3 and T4 concentrations during the treatment and the decrease in plasma ANP level. The decrease in plasma ANP was not closely correlated with the reduction of cGMP levels. These results indicate that: 1) a steep decrease in serum thyroid hormone concentrations induced by a full methimazole treatment during ten days in patients with thyrotoxicosis due to Graves' disease was accompanied by the return of elevated plasma ANP levels to normal range; 2. diminution of serum concentrations of both T3 and T4 during the treatment was correlated with the decrease in plasma ANP; 3) reduction in plasma cGMP concentration associated with short-term methimazole treatment in thyrotoxicosis seems to depend not only on the diminution of plasma ANP level.

The study was aimed at evaluation of iodized salt consumption, urinary iodine concentration and incidence of goiter in children from four districts of north-western Poland: Szczecin, Koszalin, Słupsk and Gorzów Wlkp. The study was a part of the national programme: "Investigations of iodine deficite and iodine prophylaxis in Poland". The investigations were performed in ten schools randomly selected by Coordinating Centre in Kraków. Altogether 1793 children attending these schools (838 boys and 955 girls) of age between 6 ad 13 years, living in the cities and villages of coastal and lowland region were studied. The examination included interview in the form of a standard questionnaire, physical examination of the thyroid according to the WHO criteria, ultrasonographic evaluation of thyroid volume and determination of iodine concentration in single urine specimen. It appeared that only 11.2% of children used to consume iodized salt. Mean iodine concentration in urine was 76.2 micrograms/l both in children consuming and not consuming iodized salt, indicating dietary iodine deficiency. The incidence of goiter in country population of children (12.9%), indicated that the region of north-western Poland should be considered as an area of mild goiter endemy. These results suggest a need for iodine supplementation of edible salt in this region of Poland.

The concentrations of beta-endorphin, ACTH, insulin (IRI), glucagon (IRG), cortisol and growth hormone were determined by radioimmunoassay during oral glucose tolerance test (OGTT) performed in 13 obese patients with normal glucose tolerance and without arterial hypertension. The test was performed in random, before and after intravenous administration of 0.8 mg of naloxone. Six persons with normal body weight served as controls. Higher basal concentrations of beta-endorphin and significant increase in beta-endorphin levels during OGTT, without concomitant increase in ACTH concentrations, have been found in obese patients. No effect of naloxone on beta-endorphin liberation during OGTT was observed, though the drug caused lowering in maximal increment of beta-endorphin and paradoxically lowered the concentrations of ACTH and cortisol. The basal concentrations of beta-endorphin did not correlate with the concentrations of insulin, ACTH, cortisol and growth hormone. Elevated concentrations of insulin, lowered concentration of growth hormone and normal levels of glucose and glucagon were observed in basal conditions, and excessive responses of insulin, glucose and glucagon were observed in obese patients during OGTT. Naloxone lowered insulin response and inhibited the fall of growth hormone during OGTT but did not influence the concentrations of glucose and glucagon. No correlation was found during OGTT after naloxone between insulin and beta-endorphin, ACTH or cortisol, whereas negative correlation was observed between insulin and growth hormone. The obtained results suggest that the elevated concentrations of beta-endorphin in simple obesity may be of both hypophyseal and peripheral origin. Hyper-beta-endorphinemia observed in obesity is probably not directly responsible for hyperinsulinemia, it may, however, be responsible for lower sensitivity of tissues to the action of insulin.

The early (immediately after the end of treatment) and late (from 12 to 91, mean 46.3 months after the end of treatment) results of progressive Graves-Basedow ophthalmopathy treatment were evaluated in 71 patients (57 women and 14 men, aged 25-66, mean 47.3 years). In all patients the thorough ophthalmological evaluation was performed early and late after treatment and the abnormalities found were classified according to Werner's method and Donaldson's ophthalmopathy index. The patients were divided into 7 groups according to different methods of treatment. Groups I-V consisted of 31 patients treated with glucocorticoids or glucocorticoids with azathioprine (Imuran) in the first stage of medication (30 patients). Plasmapheresis (7 patients) or tele-cobalt irradiation (3 patients) was applied as the second stage of treatment when the first stage was ineffective. In one person plasmapheresis and tele-cobalt irradiation was applied without previous glucocorticoid therapy. Two patients were treated successively by glucocorticoids, plasmapheresis and tele-cobalt irradiation. Very good and good late results of treatment were found in 95% of patients out of 22 reexamined persons of groups 1-5. Group 6 consisted of 7 patients treated with cobalt irradiation alone, in all 6 patients evaluated late results were good or very good. Out of 33 patients of group 7 treated by combination of glucocorticoids and telecobalt irradiation 23 were evaluated late and the results were found good or very good in 96%. The results suggest that combined treatment of progressive endocrine ophthalmopathy with glucocorticoids and cobalt irradiation is the most effective method of treatment at present. The affectivity of stage treatment is comparable with combined treatment but lasts longer and usually is more expansive.(ABSTRACT TRUNCATED AT 250 WORDS)

The study was carried out in 2153 children and adolescents (1066 girls and 1087 boys) aged 5-20 years. The examined group was chosen randomly, according to a simple drawing scheme. The aim of the study was to evaluate frequency, size and character of goiter in developmental age population in Szczecin's region. The goiter was found in 14% of examined population (18.4% in girls and 9.8% in boys). Frequency of goiter approximated to 37% in girls and 16% in boys during puberty spurt (between 10 and 16 year of age). Small degree of thyroid enlargement was predominant in examined population. Large goiter was present more frequent in girls than in boys. We did not find clinical symptoms of thyroid gland dysfunction in examined group. Frequency of nodular goiter was 7% of children's and adolescent's population with higher incidence in boys (9%) than in girls (6%).

Pharmacokinetic parameters of thiamazole in hyperthyroid patients (40 subjects with Graves-Basedow disease--32 female and 8 male patients) and in healthy individuals (8 subjects--5 women and 3 men) were compared. A one-compartment model was used for the analysis of examined pharmacokinetic parameters. Area under thiamazole concentration curve (AUC) and thiamazole peak plasma concentration (cmax) were significantly decreased in hyperthyroid patients in comparison with healthy individuals. An analysis of other pharmacokinetic parameters suggests that observed differences seem to depend upon lowered and retarded thiamazole absorption from the gut and acceleration of drug metabolism in hepatic microsomal system in hyperthyroid patients.

In 22 patients with progressive endocrine ophthalmopathy (classes 4-6 according to Werner's scale and ophthalmopathy index at least 4 and evidences of infiltrative changes in retro-ocular tissues in computerised tomography, after achievement of euthyroid state) the titers of antibodies against thyroid membrane antigens (ATMA) were determined by Gardas and all. method. Control group consisted of 26 patients with Graves-Basedow disease without clinical signs of ophthalmopathy who were investigated for ATMA before and after conventional methimazole treatment. The determinations of ATMA were performed before treatment, after 3-4 weeks and subsequently once a month. ATMA's titers exceeding 1:1000 were found in 68% of patients with progressive infiltrative ophthalmopathy and in 77% of patients with Graves-Basedow disease without ophthalmopathy. The incidence of elevated ATMA titers during treatment of ophthalmopathy with supervoltage retro-orbital tissues irradiation with high dose of prednisone, decreased markedly in 6th month of treatment with subsequent increase to average 55% at the end of treatment what suggests the influence of therapy on antibodies production. The changes in the incidence of elevated ATMA titers during conventional Graves-Basedow disease treatment were different. No relations between increased ATMA titers and intensity of infiltrative ophthalmopathy and the course of treatment in the patients with ophthalmopathy were found.

Alport's syndrome consists of hereditary nephritis, often progressing to renal failure, and variable neural hearing loss. It was diagnosed in dizygotic twins, aged 32 years, suffering from nephropathy manifested by microscopic hematuria, proteinuria and chronic renal failure, accompanied by hearing loss and ocular disorders (observed in both retina and lenses). Gothic palate has been noted in both patients. Glomerulitis was diagnosed for the first time at the age of 11 and 12 years, respectively. Hearing loss began in one brother 10 years later, and in another 11 years later. Renal failure developed much later. Diagnostic problems were due to the fact, that streptomycin was used in childhood (another cause of hearing loss?) and to the lack of any symptoms of Alport's syndrome in other members of the family.

Kallman's syndrome is defined clinically as hypogonadotropic hypogonadism associated with anosmia and other congenital abnormalities. There is no report on Kallman's syndrome coexisting with aortic valve anomaly and epilepsy in the available literature. Therefore, the authors considered worthy presenting a case of a 36-years male [correction of female] patient with Kallmann's syndrome combined with aortic valve anomaly, epilepsy and hyperostosis frontalis. Disease history data, clinical examination, the results of hormonal tests and USG helped to establish the diagnosis. Diagnostic and therapeutical problems in such cases have also been discussed.

Pharmacokinetic parameters of thiamazole were compared in two groups of patients with hyperthyroidism due to Graves-Basedow disease, differing in the period required to achieve clinical euthyrosis (less than 28 days, group R, n = 23, and not less than 35 days, group D, n = 18) after treatment with the "full" dose of the drug. The drug absorption from the GI tract in both groups was similar, but the serum concentrations of the drug (Cmax and AUC) were higher, and distribution volume and total clearance lower in the R than in D group. No evidence was found for the importance of initial plasma levels of thyroxine or triiodothyronine on pharmacokinetic parameters of thiamazole.

The study has been carried out on 4,565 persons (2,349 girls and women also 2,216 boys and men) aged 4-64. The examined group was chosen randomly, according to a simple drawing scheme. The aim of the study is to evaluate frequency, magnitude and character of goiter in residents in Szczecin region. The goiter has been found in 19.5% persons in examined population, so it makes possible an endemic state. In consideration of a fact that goiter appears frequently among women and there are more cases of thyroid enlargement (O-B and I degree), as well as a small number of people with disturbance thyroid function only slightly endemic character is stated. Because the frequency of modular goiter among people with goiter is 20% it doesn't express extent of endemic state.

Early results of combined use of glucocorticoid administration and irradiation with radioactive cobalt for treatment of oedematous-infiltrative ophthalmopathy associated with Graves' disease have been analyzed in a group of 33 patients including 28 women and 5 men of age between 25 and 66 years (mean age 47.3 years). The combined therapy was a modification of the original method of Bartalena et al. which consisted in the gradual increase of the initial dose of glucocorticoids and prolongation of the period of administration of the drug. The ophthalmic lesions were assessed by thorough ophthalmologic examination and classified according to Werner. The ophthalmopathy index was calculated according to Donaldson. Satisfactory results of treatment have been obtained in 32 patients, with 9 patients being completely relieved from any objective or subjective ophthalmic symptoms (very good results), and 23 patients having still small afflictions originating from the soft tissues of the eye socket, exophthalmos, diplopia during marginal vision and a decreased visual acuity (good results). The clinical recovery was mostly connected with the improvement in the condition of soft tissues of the eye socket, cornea and external ocular muscles and, to a smaller extent, exophthalmos which persisted to some degree and acuity of vision not always attaining normal values. In one person the results of treatment were unsatisfactory despite some improvement. Very good and good results obtained in 97% of patients indicate that the administration of glucocorticoids combined with the irradiation of retrobulbar tissues with radioactive cobalt can now be regarded as the most effective method of treatment of the progressive oedematous-infiltrative ophthalmopathy.