The possible impact of dialysis modality on cognitive function in chronic dialysis patients.

Chronic kidney disease (CKD) is a growing public health problem. Individuals in all stages of CKD are at higher risk for development of cognitive impairment and this may be a major determinant in their quality of life (QOL). The prevalence of cognitive deficits is particularly high in subjects with end-stage renal disease (ESRD). While it is sufficiently well documented that ESRD is linked with a change in cognitive function, little is known about the influence of different dialysis modalities on cognitive function. The effect of dialysis modality on risk of cognitive impairment is unclear. Some data suggest that patients with ESRD treated with chronic ambulatory peritoneal dialysis (CAPD) had consistently better cognitive function than patients treated with haemodialysis (HD). We concluded that the previously observed apparent difference between two modalities of dialysis treatments resulted either from very low dialysis delivery or comparison with poorly matched controls. Regarding these data from previous studies we hypothesised that well-dialysed, well-nourished and medically stable HD patients had no cognitive dysfunction in comparison with well-dialysed, well-nourished, medically stable and demographically matched CAPD patients. Also, future studies are needed to differentiate between modality as a risk factor from the factors contributing to selection bias among patients choosing CAPD over HD.

The level of anti-topoisomerase I antibodies highly correlates with metacarpophalangeal and proximal interphalangeal joints flexion contractures in patients with systemic sclerosis.

BACKGROUND: It is found that an antibody directed against DNA topoisomerase I (anti-topo I abs) is detected almost exclusively in systemic sclerosis (SSc). These antibodies are predictors of pulmonary fibrosis and peripheral vascular disease. OBJECTIVE: Metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints flexion contractures are assessed as markers of active SSc. The aim of this study was to find out is there any relationship between anti-topo I abs and MCP and PIP joints flexion contractures. METHODS: Twenty-eight patients with active disease who fulfilled the American College of Rheumatology criteria for SSc were included in this study. Twenty eight healthy control subjects were also investigated. Clinical and radiological assessments of the hands were carried out. The flexion ranges in the 8 finger joints by goniometric measurement were obtained. Anti-topo I abs with an enzyme linked immunosorbent assay (ELISA) were measured. RESULTS: MCP and PIP joints flexion contractures and the levels of anti-topo I abs were significantly higher in patients with systemic sclerosis than in healthy control. The anti-topo I abs were found in 16 of 28 patients with systemic sclerosis. Sixteen of 28 patients with active disease had MPC and proximal PIP joints flexion contractures. In 16 SSc patients with anti-topo I abs, 13 had metacarpophalangeal and proximal interphalangeal joints flexion contractures. In only 3 patients of 16 with the flexion contractures the levels of anti-topo I abs were negative. The patients with MPC and PIP joints flexion contractures had higher mean value of anti-topo I abs titers (53.718 +/-50.977 vs 8.127 +/- 8.915, P < 0.0001) than did those with no contractures. Furthermore, the titers of anti-topoisomerase I antibody positively correlated with the flexion contractures (r = 0.4252, P = 0.0241). Radiologically, joint space narrowing and flexion contractures of the fingers were seen significantly more frequently in the SSc patients with anti-topo I abs (P < 0.05). CONCLUSION: Serum level of anti-topoisomerase I antibodies is in direct relationship with MPC and PIP joints flexion contractures.

Two spent dialysate samples are sufficient for hemodialysis efficacy assessment.

INTRODUCTION: The measure of dialysis efficacy is expressed as Kt/V value (calculated from predialysis and postdialysis blood urea concentration). The aim of this study was to assess the possibility of direct calculation of Kt/V value from two spent dialysate samples by using the regular blood-based Kt/V calculation formula with dialysate samples used as surrogates for blood samples, and to detect the most appropriate couple of dialysate samples for Kt/V estimation. PATIENTS AND METHODS: Fifty-two single hemodialysis treatments in 34 anuric patients on chronic bicarbonate low-flux hemodialysis were observed. Kt/V values according to Daugirdas formula from two blood samples and from two dialysate samples were calculated. RESULTS: Kt/V values calculated according to Daugirdas 2 nd generation formula from blood samples (Kt/V sp Daugirdas) were in significant correlation with all Kt/V values obtained from two spent dialysate samples. The highest correlation coefficient (r = 0.74, p < 0.001) and the least standard error of mean of the differences were found between Kt/V sp Daugirdas and value obtained with substitution of urea concentration from dialysate samples taken 60 minutes after dialysis start and at the end of the dialysis into Daugirdas 2 nd generation formula (Kt/V D C D(60) -C D(e) ), which can be expressed as a equation of linear regression y = 0.47 + 0.86x. The highest correlation coefficient (r =0.74, p < 0.001) was found between Kt/V sp Daugirdas values equilibrated according to Daugirdas rate formula, and Kt/V D C D(60) -C D(e) value, which can also be expressed as an equation of linear regression y = 0.43 + 0.73x. CONCLUSION: The results of this study clearly show the sufficiency of only two spent dialysate samples for direct estimation of the Kt/V values, with no blood sample required.

Plasma and cerebrospinal fluid endogenous digoxin-like immunoreactivity in patients with aneurysmal subarachnoid haemorrhage.

Recent evidence indicates the presence of naturally occurring digitalis-like compounds in mammals, collectively known as either digitalis-like (DLF) or ouabain-like (OLF) factors, presumed to be endogenous hormones regulating the biological activity of the NA+/ K(+)-ATPase and its isoforms. This substance has been postulated to enhance renal tubular sodium excretion and to increase peripheral vascular resistance. Digoxin-like immunoreactive substance (DLIS) was observed in plasma of some patients with spontaneous subarachnoid haemorrhage (SSAH). Accumulating evidence suggests the central nervous system as a site of synthesis, but also as a site of hypertensinogenic action of endogenous cardioglycosides. The present study intends to establish the ratio of the DLIS in plasma to that in cerebrospinal fluid (CSF) in patients with SSAH and to investigate possible connection of this substance with development of arterial vasospasm. A prospective analysis of DLIS levels was performed on plasma and CSF samples obtained in 40 patients who had suffered a recent SSAH. DLIS levels were determined by the fluorescence polarisation immuno-assay method immediately after the admission to the Ward, and again seven days later. The comparison of CSF and plasma DLIS levels did not show statistically significant differences between the results--neither for the first (Z = 0.530; P = 0.591) nor for the seventh day after the disease onset (Z = 0.448; P = 0.654). Three possible hypothetical explanations of these results are offered: a) substance determined by digoxin immuno-assay has no essential likeness to digoxin; b) loss of the haemato-encephalic barrier integrity enabling free substance exchange between plasma and central nervous system; c) digoxin-like substance production within the central nervous system. Further, comparison of DLIS plasma levels (7th day from onset of SSAH) with angiography results showed that patients with multiple vasospasm had essentially higher plasma DLIS levels compared to patients with no vasospasms (Z = 2.59; P = 0.0097). The amount of extravasated blood, assessed on the basis of cranial CT scanning, was also connected with higher plasma DLIS levels (X2 = 3.29; P = 0.0305). The enhanced arterial narrowing which occurs in SSAH may be in part mediated by increased digitalis-like factor activity.

Diuretic effects of furosemide infusion versus bolus injection in congestive heart failure.

In a randomized, single-blind, crossover clinical trial, the diuretic efficacy of the same total dose of furosemide (2 x 40 mg) administered in either conventional intravenous bolus injection or continuous infusion was studied in 20 patients (nine males and 11 females), aged 37-75 years, with congestive heart failure. Furosemide infusion, administered first, produced a significantly greater diuresis than the bolus when compared with baseline (86%: 29.6%; p = 0.029). This was followed by a similar increase in 24-h urinary sodium, potassium and chloride excretion, with no significant difference from the bolus effect. The following day, diuretic and saluretic effects of furosemide did not differ significantly between the study groups. Nevertheless, when continuous furosemide infusion was administered first, it produced a greater increase in urinary volume, 24-h urinary sodium, potassium and chloride than when bolus injection was applied the next day. Conversely, when furosemide bolus was administered first, followed by the infusions the next day, the effects were almost equal, regardless of the mode of administration. It is concluded that in the treatment of refractory edema in patients with congestive heart failure, continuous intravenous infusion of furosemide is superior to the conventional intermittent bolus injection, especially if it is administered at the very beginning of the hospital treatment, and presumably is even better with higher dosage and longer infusion time span.

Comparison of chlorthalidone, propranolol and bopindolol in six-month treatment of arterial hypertension.

The aim of this study was to test the hypothesis that prolonged treatment of mild to moderate hypertension with low-dose thiazide diuretics or beta blockers does not induce any of the major untoward biochemical changes, such as hypertriglyceridemia, hypercholesterolemia, hyperuricemia and electrolyte imbalances. The effect of these drugs was analyzed in 100 outpatients (52 males and 48 females) aged 52.0 +/- 7.9 years with mild to moderate hypertension, in a prospective 6-month study. After an appropriate workup, the patients were randomized to either 25 mg chlorthalidone (40 patients), 120 mg propranolol (30 patients), or 2 mg per day bopindolol (30 patients). A significant reduction of approximately 10% in systolic and diastolic blood pressure was recorded in all the groups. At the end of the 6th month, in the chlorthalidone group triglycerides increased to 3.0 +/- 2.1 mmol/l from 2.8 +/- 1.6 mmol/l, while cholesterol after an initial increase to 6.6 +/- 1.6 from 6.4 +/- 1.6 mmol/l returned to the baseline level. Uricemia and serum potassium concentration decreased by 4%. The body weight was reduced to 83.8 +/- 13.4 kg from 86.1 +/- 13.4 kg. There was no change in serum glucose level. In the propranolol group, as expected, heart rate decreased by 20%, but there were no significant changes in glucose and potassium plasma concentration. Triglycerides did not change significantly, while cholesterol, after a small increase, returned to the initial levels. Similar results were obtained in the bopindolol group, apart from the triglycerides, which increased significantly (to 2.5 +/- 1.1 from 2.2 +/- 0.4 mmol/l), probably because of the lower baseline concentration. We conclude that in prolonged treatment, chlorthalidone, propranolol and bopindolol do not induce significant untoward biochemical changes that alone might increase cardiovascular risk.

QT interval as a marker of venous reactivity in dialysis patients.

Fourteen patients (7 females and 7 males, mean age 51.9 +/- 11.6 years) were studied to find out whether there is a connection between the QTc interval (a diagnostic tool for evaluating autonomic neuropathy) and venous reactivity in uremics on chronic hemodialysis. The QT interval was measured using standard lead II as reference, corrected for heart rate, and designed QTc. Venous reactivity was measured by the so-called venoconstriction test. Pressure changes inside the vein were obtained by injection of 2 micrograms of noradrenaline, and expressed in venoconstrictive units (VCU). The mean QTc was 445.7 +/- 36.9 ms. The mean venous tone response was 2130.9 +/- 1435.5 VCU. There was a significant correlation between the QTc interval and venous reactivity to catecholamine (r = 0.565, P = 0.03). It is concluded that the QTc interval may be used as a marker of venous tone reactivity, suitable for everyday clinical practice. Furthermore, the magnitude of this reactivity possibly represents either the end-organ or peripheral sympathetic impairment.

Two new cases of liver angiosarcoma: history and perspectives of liver angiosarcoma among plastic industry workers.

In this report of two new cases of liver angiosarcoma (ASL) among plastic industry workers, the authors present the history and perspectives of this problem. The first cases of ASL have been registered since 1974, and in 1984, the European register of angiosarcoma was founded. In this register, 11 cases of ASL and one case of haemangiopericytoma have been registered from Croatia, all from a single plastics plant near Split. Two new cases of ASL (in retired autoclave cleaners, who were exposed to a concentration of 500-1000 ppm vinyl chloride monomer (VCM) during the working process) in the same plant are represented. They were detected with combined techniques of ASL detection, and both are still alive. The diagnoses have been histologically confirmed: one of them was surgically treated with segmental liver resection. The appearance of new cases of ASL confirms the perspective presented in the last report by the same authors.

Effect of therapeutic interventions on CK and CK MB serum activity kinetics during acute myocardial infarct.

Determination of serum creatine kinase (CK) activity, especially the CK MB, isoenzyme is becoming the main diagnostic criterion for acute myocardial infarct (AMI). The aim of this study was to assess the kinetics of the release CK and CK MB in AMI patients on various therapeutic regimens. The study included 75 AMI patients (within 6 hours from the pain onset). They were divided into three groups according to therapy: 1.NTG i.v. (glyceryl trinitrate, N=29), 2.SK + NTG i.v. (streptokinases + glyceryl trinitrate, N = 29); and 3. SK i.v. (N = 17). Samples for CK and CK MB determination were taken every 4 hours in the course of 72 hours, until serum enzyme values returned to normal. The time interval between the introduction of therapy and CK and CK MB peak values expressed in rankes was the shortest in group 3 and longest in group 1. The difference in maximal CK release in to peripheral blood (chi 2 = 9.5270, p = 0.0180) was statistically significant, while difference in CK MB was not (chi 2 = 2.2733, p = 0.2875--NS) (Kruskal Wallis one way test). Comparing CK release time the CK MB within each group by means of rankes, statistical significance in favour of CK MB (1. NTG i.v. p = 0.0000, 2. SK + NTG p = 0.0001, 3. SK p = 0.0180) was obtained. The rate of CK and CK MB elimination from the circulation, expressed as fractional level of losing kd, did not statistically differ in the three groups. Authors' results showed the therapeutic procedures used in the treatment of AMI patients to differently influence the CK and CK MB kinetics. Thrombolytic therapy changed the CK and CK MB kinetics, due to reperfusion and explained by the washout phenomenon from the infarcted zone of the myocardium.

Acute renal failure as a complication of acute pancreatitis.

To assess the prevalence of acute renal failure (ARF) in patients with acute pancreatitis, as well as the factors predictive of a lethal outcome, we retrospectively studied the data of all patients admitted to our hospital over a 5-year period. Between 1989 and 1993, 554 patients presented with acute pancreatitis, of which 24 (4.4%) subsequently developed ARF. Death occurred in 14/24 (58%) of patients with ARF, and was associated with an increased incidence of multiorgan failure. There was no statistically significant difference in the age, admission blood pressure, or admission pulse rate of the patients who survived and those who died. In contrast, death was associated with a higher Ranson score, and the increased prevalence of multiorgan failure. The length of hospitalization of the nonsurviving group was significantly shorter. Acute renal failure is not a common finding in patients with acute pancreatitis. However, when it occurs, it is associated with a poor prognosis, and is predicted by a higher Ranson score and the presence of multiorgan failure.

[Biochemical changes in hypertensive patients during a 1-year cross-over study of treatment with hydrochlorothiazide and propranolol]. / Biokemijske promjene u hipertonicara tijekom jednogodisnjeg krizanog lijecenja hidroklorotiazidom i propranololom.

A prospective, randomized, cross-over trial comparing the antihypertensive efficacy and biochemical changes during treatment with either hydrochlorothiazide (HTZ: 25 mg o.d.) or propranolol (PRO: 40 mg t.i.d.), included 55 mild to moderate hypertensives (diastolic blood pressures ranged from 90 to 110 mmHg), aged 25-65 years. Forty patients completed the study; during the first six months 20 of them (12 males and 8 females) were taking HTZ, and the remaining 20 (13 males and 7 females) PRO. After a one-week wash-out period, for the next six months the alternative drug was administered. Antihypertensive efficacy of both drugs was nearly equal: systolic and diastolic blood pressure significantly decreased already after the first month (approximately by 10%), and kept unchanged until the end of the study. The analyzed biochemical parameters, i.e. blood glucose, cholesterol, and triglycerides did not increase significantly, while serum potassium level remained almost unchanged during the trial. Furthermore, during PRO in group B, cholesterol significantly decreased (3rd month), as well as blood glucose during HTZ treatment (10th month). Only the uric acid level, although unsignificantly, increased in group A (from 326.2 to 365.3 +/- 125.2 on HTZ, and to 391.4 +/- 120.0 mumol/l on PRO). It is concluded that HTZ and PRO are comparably effective antihypertensives. During the long-term treatment in small doses these drugs do not induce significant biochemical disturbances.

Vinylchloride monomer exposure by the plastic industry workers basic condition for liver angiosarcoma appearance.

The retrospective study of vinylchloridemonomer (VCM) exposure at 37 workers in the period from 1969 till 1987 was done, average time of exposition was 1.843 +/- 1.105 h, average VCM concentration was 543 +/- 228 ppm and average total exposure amount ("cumulative concentration of VCM") was 1.103811 +/- 1.050 766 ppmh at the time of autoclave cleaning 0.4 +/- 0.1 h. According updata investigations, high VCM concentration is essential for liver angiosarcoma (ASL) occurrence although the length of exposure is of concern. The possibility of new cases of angiosarcoma of liver is warned about.

Ramipril decreases chlorthalidone-induced loss of magnesium and potassium in hypertensive patients.

A double-blind clinical trial was conducted to compare the efficacy of and electrolyte changes caused by ramipril-chlorthalidone combination treatment (5 mg + 25 mg) and chlorthalidone monotherapy (25 mg daily) in patients with hypertension. After a 4-week placebo period, 32 patients (mean age, 51 +/- 9 years) with essential hypertension (average blood pressure of 181.4/104.5 +/- 13.0/6.9 mmHg) were randomly assigned to receive combination therapy (group A, n = 17) or monotherapy (group B, n = 15). After 12 weeks of active treatment, systolic and diastolic blood pressure decreased by 16.1% and 13%, respectively, for patients taking combined therapy, and by 12.7% and 9.8%, respectively, for patients taking monotherapy. The difference was significant for between-group comparisons. There were no changes in serum sodium concentration, but a significant similar increase in 24-hour urinary sodium excretion was seen in both groups. Serum calcium levels increased slightly and 24-hour urinary calcium excretion decreased significantly in both groups, probably due to chlorthalidone administration. Serum potassium levels increased slightly in group A (from 4.16 +/- 0.39 mmol/L to 4.30 +/- 0.42 mmol/L) and decreased slightly in group B (from 4.18 +/- 0.32 mmol/L to 3.99 +/- 0.49 mmol/L). Urinary potassium excretion did not change significantly in group A, but increased by approximately 15% in group B. There was a decrease in 24-hour urinary magnesium excretion (from 4.01 +/- 1.24 mmol/24 hours to 3.50 +/- 0.93 mmol/24 hours) in group A and an increase (from 3.49 +/- 0.98 mmol/24 hours to 4.35 +/- 1.12 mmol/24 hours) in group B. At the end of the trial these changes were significant in between-group comparisons. Consistent with the previously shown amelioration by ramipril of thiazide-induced metabolic side-effects, ramipril appears to improve magnesium balance during cotreatment with chlorthalidone.

The effect of intravenous nitroglycerin therapy on infarct size in patients with acute myocardial infarction.

The authors investigated the influence of glyceryl-trinitrate (NTG) given intravenously to the reduction of infarction size in 95 patients (71 men and 24 women) aged 36 to 75, with acute myocardial infarction (AIM) admitted to the Intensive Care Unit within six hours of the onset of pain. Infarction mass was calculated by mathematical model from the serial changes of CK and CK MB serum activities during 72 hours and expressed in CK and CK MB gEq. CK and CK MB were determined every four hours. The patients were divided into four groups according to the therapy they were receiving: I--NTG i.v. (n = 29); II SK + NTG i.v. (n = 29); III SK i.v. (n = 17) and IV ISDN per os (n = 20). Each group was divided into subgroups regarding the time interval from the onset of pain to the beginning of the therapy (within three hours and after three hours). Application of NTG i.v. in the early phase of AIM, 0-3 hours from the onset of pain, led to the significant reduction of infarction mass CK gEq and CK MB gEq (0-3 hours; middle rank = 11.35; 3-6 hours: middle rank = 17.7) (P < 0.05) and 0-3 hours: middle rank = 10.31; 3-6 hours: middle rank = 18.81 (P < 0.01). It was established that the "timing" factor was very important in the preservation of myocardial mass in AIM. It affirms the efficacy of NTG i.v., i.e., its direct effects on the coronary arteries and systemic effects that cause salvation of the myocardium. The influence of NTG iv to myocardial infarction size CK gEq did not depend on ECG localization. But it influenced the ECG localization when the infarction size was calculated from CK MB isoenzyme and expressed in CK MB gEq. Infarction mass CK MB gEq was statistically significantly smaller in the inferior than in the anterior localization (P < 0.05).