[Refractory arterial hypertension--where is the refractoriness? Hic rhodus, hic salta!]. / Refraktorna arterijska hipertenzija--u cemu je tvrdokornost? Hic rhodus, hic salta!

Arterial hypertension (AH) is the major independent risk factor for cardiovascular and cerebrovascular morbidity and mortality. Success in treatment of hypertonic patients is currently still far from acceptable in developing countries but also in the most of the developed countries in the world. There are numerous reasons and explanations for such poor therapeutic outcome, with poor patient's awareness of the need to pay attention to his own health and occasional superficial physician's approach being only some of them. However, AH treatment may present as an exceptional problem in some patients. Despite sufficient therapy duration and optimal doses of three types of antihypertensives, including one diuretic, no decrease in arterial blood pressure was observed in a low number of patients, so that such AH is called refractory (RH). RH may be primary if present since the beginning of treatment, or secondary if presenting after a period of successful treatment. In case of secondary RH, secondary forms of AH should be considered, like renovascular hypertension, primary aldosteronism, etc. In cases of primary RH, it is necessary to exclude pseudohypertension, pseudoresistance and pseudotolerance before characterizing a patient as really resistant, when the cause should be primarily sought in pathomechanisms of those organ systems which otherwise play an important role in AT homeostasis or in etiopathogenesis of AH, i.e. in kidney and heart. A significant reason for refractoriness may be drug interactions or applications of hypertensives which are not an optimal choice according to hemodynamic or hormone background of increased blood pressure. Clearly, it is not always easy to determine the background of refractoriness in practice, yet fortunately such patients are not frequent and additional efforts dedicated to them are not at the time needed for other patients. In this paper we presented a review of the most frequent causes of refractoriness in AH treatment, possible errors in diagnosing RH, and pathomechanisms responsible for the occurrence of resistance. Prognosis of RH is considerably worse than in otheR hypertonic patients and, since the possibilities of treatment are not extensive, a review of possible therapeutic approaches is also presented depending on the pathogenetic background of resistance. As RH patients have increased body mass index, and the success of the therapy was observed to depend on the salt intake, particular attention should be paid to instructions for patients on the change in lifestyle. The treatment of RH patients is a serious challenge which may unfortunately be frustrating and not infrequently have a fatal outcome due to either disease progression or patient's obstinacy.

Immunohistochemical analysis of human serum sickness glomerulonephritis.

AIM: To analyze pathological and immunohistochemical characteristics of glomerulonephritis in human serum sickness. METHODS: Renal biopsy specimens from two female patients with serum sickness that ensued after application of anti-lymphocyte horse globulin for aplastic anemia were analyzed by light microscopy, immunofluorescence, and electron microscopy. To prove the depositions of foreign protein, frozen sections were incubated with fluorescein-conjugated anti-horse protein serum. Immunohistochemical analysis was performed on B5-fixed paraplast-embedded tissue or frozen acetone-fixed sections with the primary antibodies for molecules/cell markers CD35, CD43, CD45RO, CD68, CD2, lysozime, L26, and S100. RESULTS: Diffuse proliferating and necrotizing glomerulonephritis with crescents was found. There were coarse granular mesangial, subepithelial, subendothelial, and intramembranaceous deposits of mainly horse globulin, C3, and IgG. Most mesangium infiltrating cells were macrophages and T-lymphocytes. Electron microscopy revealed hypertrophy of podocytes, but immunohistochemistry did not show their normal CD35 (C3b-receptor) staining. Apart from epithelial cells, main crescent forming cells were macrophages and T-lymphocytes. Rare dendritic cells and abundant infiltration of macrophages, T-lymphocytes, and neutrophiles were found in the interstitium. CONCLUSION: In severe serum sickness, glomeruli and tubuli are destroyed beyond the range usually seen in other types of glomerulonephritis caused by immune complexes, except in cases with widespread crescents. Hypertrophy of podocytes and loss of their normal C3b-receptor staining has not yet been described in the literature. C3b-receptors on podocytes could play a role in pathogenesis of glomerular injury caused by immune complexes.

[Epidemiology of arterial hypertension in Croatia in 2000]. / Epidemiologija arterijske hipertenzije u Hrvatskoj 2000. (EH-UH 2000).

Arterial hypertension is one of the most important modifiable risk factors for cardiovascular disease. Treatment of hypertension has been shown to decrease the risk of myocardial infarction, stroke, congestive heart failure, end-stage renal disease and peripheral vascular disease. It is apparent from some results that blood pressure should be lowered in all patients having other cardiovascular risk factors regardless whether they are hypertensive or non-hypertensive persons. However, complete information considering awareness, treatment and control of arterial hypertension is still missing. The aim of our study is to obtain these data for the entire region of the Republic of Croatia. The study will be finished in two years and new hypertension related cardiovascular risk indicators such as isolated systolic hypertension, pulse pressure and heart rate will be analysed as well. Therapeutic success will be analysed in particular subpopulations considering applied therapy.

Complete remission of cryoglobulinemic glomerulonephritis (HCV-positive) after high dose interferon therapy.

We report the case of a 64-year old woman with hepatitis C virus infection, mixed cryoglobulinemia type II (IgG + IgM kappa) and cryoglobulinemic glomerulonephritis. The patient was treated with the standard dose of recombinant interferon alpha-2b (3 million units 3 times a week) for one year, resulting in complete clinical remission and undetectable levels of serum hepatitis C virus RNA. AST and ALT normalized and proteinuria decreased from 2.78 to 0.98 g/day. However, a relapse occurred when therapy was stopped. Additional therapy with interferon-alpha (5 million units 3 times a week for 9 months) resulted again in quick and prolonged remission. The clinical course of our patient showed sustained clinical and virologic response after high-dose interferon-alpha treatment confirming the usefulness of interferon alpha in treatment of patients with cryoglobulinemic glomerulonephritis. Our observation is in agreement with others, suggesting that recommended standard dosage and duration of initial treatment with interferon alpha should be re-evaluated. Although our patient had sustained virologic and clinical response after interferon alpha monotherapy, recent studies clearly support combination therapy of interferon alpha and ribavirin for treatment of chronic HCV infections.

Antibodies to Tamm-Horsfall protein in endemic nephropathy.

BACKGROUND: The aim of the study was to investigate the possible role of antibodies to Tamm-Horsfall protein (anti-THP) in the early diagnosis of endemic nephropathy (EN). METHODS: Anti-THP (IgA, IgM, IgG classes) antibodies were determined by direct ELISA in a random sample of 159 subjects from the endemic village of Kaniza who were divided into four groups according to the WHO criteria, i.e., 'diseased', 'suspect', 'at risk', and 'others'. These groups were compared to subjects from the non-endemic village of Klakar and healthy subjects from Zagreb. RESULTS: No differences for all the classes of antibody were observed among the groups of subjects from the endemic village of Kaniza (P>0.05) or between these subjects and those from the non-endemic village of Klakar (P>0.05). The values of IgM anti-THP antibodies exceeded those of the IgA and IgG classes in all groups of subjects (P<0.05). The values for all three classes of antibodies were higher in the rural than the urban population (P<0. 05). CONCLUSION: Determination of anti-THP antibodies was not found to be useful in the early diagnosis of endemic nephropathy. The results suggest that most of the anti-THP antibodies are 'natural' and/or cross reactive. The highest values observed in the rural population could probably be explained by exposure to some ubiquitous antigen or more likely they are consequences of fever.

Antibodies to Tamm-Horsfall protein in patients treated with extracorporeal shock wave lithotripsy (ESWL).

The aim of this study was to determine antibodies to Tamm-Horsfall protein in patients with nephrolithiasis treated with extracorporeal shock wave lithotripsy (ESWL). The values of antibodies to Tamm-Horsfall protein were determined by direct enzyme immunoassay. No statistically significant differences (P > 0.05) were observed for the IgG and IgM classes of antibodies between the groups of healthy subjects and patients with nephrolithiasis before, and 30 and 60 days after ESWL. The values of IgA class determined 30 days after treatment were significantly higher (P < 0.05) in patients, which could be due to the stimulation of the immune system. The highest values of antibodies to Tamm-Horsfall protein were obtained in both groups in the test with secondary antibodies directed toward IgM class, implicated at the presence of cross-reactive antibodies. Determination of antibodies to THP subunits isolated form urine of patients with nephrolithiasis should be performed.

Antibodies to Tamm-Horsfall protein subunits prepared in vitro, in patients with acute pyelonephritis.

The aim of this study was to determine antibodies to Tamm-Horsfall protein subunits in patients with acute pyelonephritis. The protein subunits used in this determination were prepared by chemical treatment of Tamm-Horsfall protein isolated from the urine of healthy individuals. Values for IgG and IgA were significantly higher (p < 0.05 and p < 0.01 respectively) in patients than in healthy persons, while IgM class antibodies were significantly higher only in the test performed with subunits obtained with 8.3 mol/l acetic acid (THP-A) (p < 0.05). Values for all three classes determined in the test with THP-A were significantly higher in patients with vesicoureteral reflux than in patients with normal radiological findings (p < 0.05). Antibodies to Tamm-Horsfall protein subunits isolated from the urine of patients with acute pyelonephritis should also be determined.

[Hyperinsulinemia and arterial hypertension]. / Hiperinzulinemija i arterijska hipertenzija.

Data concerning hyperinsulinemia/insulin resistance in the pathogenesis of essential hypertension are presented. Approximately 50% of hypertensive patients have insulin resistance. The prime site of insulin resistance is in the skeletal muscle affecting non oxidative glucose metabolism (glycogen synthesis). Effects of insulin on the kidney points toward possible, but not the key role of the hyperinsulinemia in the pathogenesis of arterial hypertension. According to some results hypertension causes hyperinsulinemia/insulin resistance through hemodynamic alterations and structural changes of blood vessels. On the other hand, there is no hyperinsulinemia in the secondary forms of arterial hypertension. This is an argument against hypertension as a prime cause in insulin resistance inception. The importance of metabolic alterations of lipid status and fibrinolytic system in patients with hyperinsulinemia has been emphasized. These metabolic changes increase cardiovascular risk. Effects of antihypertensive drugs on glucose metabolism and insulin sensitivity are reported. In conclusion, hyperinsulinemia per se is not a risk factor. However, when connected with other metabolic disturbances (dyslipidemia, hypertension, hyperuricemia, disorders of fibrinolysis) it increases the risk of cardiovascular diseases.

[An increase in plasma digoxin levels after discontinuation of therapy]. / Porast koncentracije digoksina u plazmi nakon prekida terapije.

In this paper, a course of the disease of a 68-year-old patient treated with medigoxin for congestive heart failure is presented. After being withdrawn from his treatment at the hospital, the patient was administered spironolactone and furosemide. The plasma digoxin level at entry was 1.1 nmol/L, after five days it reached 3.2 nmol/L, and after ten days it was 2.3 nmol/L. The patient had a normal renal function. The interference of spironolactone and its metabolites with the digoxin radioimmunoassay was discussed as a possible explanation for this phenomenon.

Eosinophilia caused by iodinated radiographic contrast media.

Statistically significant eosinophilia was noted in the peripheral blood of a group of 108 patients 48 h after the administration of iodinated radiographic contrast medium (RCM). The duration of eosinophilia was approximately 6 days. Eosinophilia had no accompanying clinical symptoms except for two cases where urticaria appeared. The incidence of eosinophilia was irrespective of dosage or type of RCM. Possible mechanisms responsible for eosinophilia have been considered. Since eosinophilias of other aetiologies are common, it is of practical importance to distinguish these from RCM-induced eosinophilias.