Influence of betaxolol and timolol on the venous tone in glaucoma patients.

The aim of this study was the assessment of physiological venous reflexes in 40 glaucoma patients treated with topically applied timolol maleate 0.50% and betaxolol HCL 0.50%. They were divided into two groups of twenty each; one group being given timolol and the other betaxolol. The assessment of the venous tone was performed by testing venous reflexes. We found no statistically significant difference between timolol and betaxolol; however, when the influence of circulating catecholamines and the other vasoactive substances was excluded by suprasphygmatic insufflation of a pediatric cuff, a significant difference was found in the Valsalva's maneuver (125.5 +/- 8.1 vs 85.0 +/- 34.3 venoconstrictive units VCUs, p = 0.03). The IOP was significantly decreased in both treatment group, although the pressure reduction effect was more pronounced in the timolol group. Our study suggests that timolol and betaxolol have a slightly different mode of action on the venous side of circulation under topical medications. It is possible that the use of betaxolol topically may reduce a systemic venoconstriction.

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.

[Occurrence of thromboembolic complications in patients with dilated cardiomyopathy. Retrospective-prospective study]. / Ucestalost tromboembolijskih komplikacija u bolesnika s dilatacijskom kardiomiopatijom. Retrospektivno-prospektivna studija.

The purpose of the present study was to determine the prevalence of thromboembolic events in patients with primary and secondary (ischemic) dilated cardiomyopathy (DC), with regard to basic rhythm, sinus or atrial fibrillation. Retrospectively, over three years, from January 1, 1989 to December 31, 1991, the case histories of 75 inpatients with DC, mean age 56.2 +/- 14.1 years, 41 in sinus rhythm and 34 in atrial fibrillation from Clinic Hospital Split were analyzed and compared to those of 75 controls (heart failure with no DC). The incidence of thrombi, embolisms and mortality in both subgroups was similar, while the prevalence of thromboembolic events was significantly higher in the analyzed than in the control group (decompensated patients with ischemic cardiomyopathy and without cardiomegaly) (9/75:1/75, p < 0.05). Prospectively, between 9 and 22 months, from December 1, 1991 to September 30, 1993 51 consecutive decompensated outpatients with DC, in NYHA class II and III, mean age 54.2 +/- 15 years, were followed-up. Bilirubin, lactic dehydrogenase, prothrombin time and activated partial thromboplastin time were determined. 1-D and 2-D transthoracic echocardiographic exam was performed and clinical status was assessed. There were 24 patients in sinus rhythm and 27 patients in atrial fibrillation. The prevalence of thromboembolic events, thrombi and mortality in both subgroups was similar. The laboratory findings, indicators of possible thrombogenesis or thrombolysis, did not show any significant difference in both subgroups. The incidence of thrombi in both parts of this study was low, amounted to only 9.5% (12/126) with no clear signs of thromboembolism (these patients were anticoagulated!). Altogether 12.6% (16/126) patients suffered thromboembolic events, 9 in retrospective and 7 in prospective part of the trial (more patients were anticoagulated in prospective then in retrospective study, 5 versus 19; p < 0.05). We conclude that thromboembolism in patients with decompensated DC are rare, but appear at significantly higher rate than in decompensated patients with ischemic cardiomyopathy and no cardiomegaly. The beneficial effects of anticoagulant therapy are to be expected in these patients regardless of the basal rhythm. This hypothesis must, however, be assessed in a prospective, multicentric trial.

[Significance of right ventricular dimensions in the differential diagnosis of primary and secondary dilated cardiomyopathy]. / Znacenje promjera desne klijetke u differencijalnoj dijagnostici primarnih i sekundarnih dilatacijskih kardiomioptija.

Numerous analyses are used in the differential diagnosis between primary and secondary dilated cardiomyopathy (PDC, SDC). The aim of this study was to assess the dimensions of heart cavities in patients with dilated cardiomyopathy (DC) by 1-D and 2-D echocardiography. Thirty-six consecutive patients who satisfied the PDC criteria, and 103 patients with criteria of SDC, were followed-up clinically, radiographically, electrocardiographically and by 1-D and 2-D echocardiography, in the period from December 1991 to April 1994, at the Department of Internal Medicine of the Clinical Hospital Split. The patients with PDC were significantly younger than those with SDC (44.4 +/- 10.4: 64.4 +/- 8.4 year). There were significantly more males than females in both DC subgroups. NYHA classification, sinus rhythm and atrial fibrillation did not differ considerably in both DC subcategories. The etiologic factor was ischaemic DC in 85.4% (88/103), systemic arterial hypertension in 11.6% (12/103), and thyrotoxicosis in 2.9% (3/103) of patients with SDC. Alcoholic DC in one patient, peripartal DC in two female patients and viral myocarditis in six patients with PDC were suspected. In the total of 75% (27/36) patients with PDC, a clear etiological factor in case histories was not defined. Left ventricular ejection fraction, diameter and myocardial thickness, as well as left atrium diameter, did not differ significantly in patients with PDC, at variance with SDC patients. Right ventricular enddiastolic diameter (31.55 +/- 4.8 mm: 26.62 +/- 8.6 mm, p < 0.05) and the ratio between enddiastolic diameters of the right and left ventricle were significantly larger in patients with PDC than in those with SDC (0.45 +/- 0.03: 0.37 +/- 0.05, p < 0.05). We conclude that right ventricle is significantly wider in PDC than in SDC patients. Compared with other noninvasive methods, 1-D and 2-D echocardiography is probably the method of choice (particularly in our environment) in the differentiation of primary and secondary DC.

Venous tone in glaucoma and hypertension.

The aim of this study was the assessment of physiological venous reflexes in systemically hypertensive and normotensive subjects with primary open-angle glaucoma. The experimental group consisted of 20 normotensive and 20 untreated systemically hypertensive patients with open-angle glaucoma. The control group consisted of 31 volunteers divided into two subgroups: 16 control normotensives and 15 untreated hypertensives. The assessment of venous tone changes was performed by testing venous reflexes. Venoconstriction responses to physiological stimuli were significantly decreased in normotensive glaucoma patients, compared to normotensive controls [for the Valsalva manoeuvre 93.4 +/- 80.2 vs. 413.3 +/- 335.4 venoconstrictive units (VCUs), p = 0.02, and for a deep breath 89.1 +/- 100.1 vs. 316.8 +/- 343.2 VCUs, p = 0.03]. The intensity of venous reflexes in hypertensive glaucoma patients did not differ significantly from that seen in hypertensive controls, due to a significantly weaker flex venoconstriction in hypertensive controls when compared to normotensive controls subjects. This study confirmed the presence of venous dysregulation in subjects with primary open-angle glaucoma and visual field loss as a part of an autonomic dysfunction. Systemic hypertension does not make this condition worse.

Venous reflex testing in glaucoma.

The aim of this study was the assessment of physiological venous reflexes in open angle glaucoma. The study was carried out by a controlled clinical experiment. The experimental group consisted of 17 glaucoma patients with controlled intraocular pressure. The control group consisted of 15 healthy volunteers. The assessment of venous tone changes was performed by means of the test of "venous reflexes". Venoconstriction responses to physiological stimuli were significantly decreased in glaucoma patients (p < 0.05). The results suggested venous dysregulation as part of sympathetic dysfunction in glaucoma.

[Comparison of auscultation findings using a classic stethoscope (Litmann 2120) and electronically amplified stethoscope (Medmax2)]. / Usporedba auskultacijskih nalaza stetoskopom s elektronskim pojacalom (Medmax2) prema klascnom (Litmann 2120).

Heart auscultation has one of the key roles in beside diagnosis, especially in patients with cardiovascular diseases. Sometimes, because of the human cars' low sensitivity, a problem emerges in the proper evaluation of heart sounds and murmurs of lower frequencies. Our study compared two stethoscopes, the classic acoustic stethoscope (Littmann 2120) and an electronic one with the sound amplifier and the noise filtering system (Medmax2) in 10 patients examined by 10 physicians. Significantly better detection of low frequency sounds was found in favour of electronic stethoscope (chi 2 = 17.9; p < 0.0001). It is concluded that the selective amplificator improves the stethoscope performance and has its place in everyday bedside practice, especially in departments of cardiology.

[A controlled clinical trial of methylprednisolone in patients with the cholestatic form of alcoholic liver cirrhosis]. / Kontrolirano klinicko ispitivanje metilprednisolona u bolesnika sa kolestatskim oblikom alkoholne ciroze jetre.

Fourty patients with alcoholic liver cirrhosis and refractory hyperbilirubinaemia were included in a prospective, double blind, comparative trial. Twenty of them were randomized to methylprednisolone (1 mg/kg/day i.m. over 3 days), and 20 to placebo (saline) of identical shape. In the active group a significant decrease in the bilirubin level (from 248 to 191 mumol/l, a drop by 23%; p < 0.05) was observed, which was not the case in the control group (from 292 to 300 mumol/l, an increase by 2.7%; p > 0.05). A decrease in the alkaline phosphatase activity was observed in both groups (by 11% in the active and by 20% in the control group: p < 0.05) while the encephalopathic indices did not improve in either. It is concluded that a short course of corticosteroid could speed-up the hospital stay and possibly slow down the progression of alcoholic cirrhosis.

[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.

Vascular effects of chlorthalidone in mild hypertensives.

In a randomized trial with chlorthalidone, 30 hypertensive outpatients of both genders, aged 50.4 +/- 8.6 years, having diastolic blood pressure between 95 and 110 mm HG were divided into 2 groups of 15, after a two-week placebo period. The A group received chlorthalidone in a single dose of 23 mg for one month, and the next month was given a 12.5 mg alternative dose, whereas the B group was given 12.5 mg in the first month and 25 mg in the second. Changes in vascular reactivity were measured by occlusive plethysmography (mercury strain-gauge) at the ends of the placebo period, the first and the second month of therapy. All the observed parameters, i.e. rest flow, peak flow, venous capacity, and maximal venous outflow, were found to have increased with 25 mg chlorthalidone, and similar findings were registered when 12.5 mg of the drug were given. Venous capacity increased significantly in both groups (from 2.6 to 3.2 and from 3.0 to 3.4 ml/100 ml). The peak-flow values augmented significantly only in the group where 25 mg of chlorthalidone were given first (from 18.6 to 23.9 ml/100 ml/min). Both doses had a similar antihypertensive effect, decreasing the mean arterial pressure by some 8% in the upright, sitting, and supine position. It is concluded that the antihypertensive effect of chlorthalidone is, at least partly, due to changes in vascular reactivity; vasodilation is more prominent on the venous side of the circulation. Low-dose chlorthalidone is equipotent as antihypertensive, its side-effects are rare, and the cost of such a therapy is by far the lowest.

[The vasodilating effect of chlorthalidone in mild hypertension evaluated by impedance venous plethysmography]. / Vazodilatacijsko djelovanje klortalidona u blagih hipertonicara vrednovano zapornom venskom pletizmografijom.

Thirty hypertensive outpatients of both sexes having diastolic blood pressure below 110 mmHg were included in a randomized trial. Their mean age was 50.4 +/- 8.6 years. After a two-week placebo period, the patients were treated with chlorthalidone in a single daily dose of 25 or 12.5 mg over the one-month period, and the next month the alternative dose (i.e. 12.5 or 25 mg) was administered. Changes in vascular reactivity were measured by occlusive plethysmography (mercury strain-gauge) at the end of the placebo period, and then post the first and second month of therapy. All the observed parameters, i.e. rest flow (RF), peak flow (PF), venous capacity (VC), and maximal venous outflow (MVO) increased with 25 mg of chlorthalidone, and similar findings were registered when a dose of 12.5 mg was given. There was a significant increase in venous capacity of both groups (from 2.6 to 3.2 and from 3.0 to 3.4 ml/100/min) and in peak flow of the group that was on 25 mg of chlorthalidone as the first dose (from 18.6 to 23.9 ml/100ml/min). Both doses had similar antihypertensive effect. It is concluded that antihypertensive effect of chlorthalidone is partly due to changes in vascular reactivity in the sense of vasodilation which is more prominent at the venous side of the blood flow, Low-dosed chlorthalidone is equipotent in antihypertensive efficiency, its side effects are rare, and the cost of therapy is by far the lowest.

Q-T interval as predictor of serum calcium level.

To assess whether measurement of the electrocardiograhic (ECG) Q-T interval is a useful predictor of total serum calcium concentration, 15 uraemic patients were studied (10 female, five male; age range, 25-60 years). Resting ECGs were interpreted by three independent observers without knowledge of the patients' identity or serum calcium. Three variants of measurement of the Q-T interval were analysed, of which Q-aTc, the interval from the beginning of the Q-wave to the apex of the T-wave, was the most consistent (coefficient of variation, 2.7%). This also provided the best correlation with measured serum calcium concentration (P < 0.001). When compared to biochemical measurements, the predicted serum calcium concentration was within 95% confidence limits in 14 of the 15 patients studied. However, the wide confidence limits of this technique mean that it cannot be recommended in routine clinical practice.

[Association of platelet aggregation with the extent of myocardial infarction]. / Povezanost agregabilnosti trombocita s velicinom infarkta miokarda.

The aim of this study was to evaluate the association between the type of myocardial infarction (MI) and the circulating platelet aggregates [circulating aggregates of thrombocytes (CAT)]. The size of MI was assessed by the maximal values of creatine-kinase (CK). In 80 patients in the acute phase of MI the values of CAT and CK were manifold increased, mostly in 30 patients with anteroseptal MI (CAT 34.1 +/- 8.3%, CK: 920 +/- 340 IU), less markedly in 30 patients with inferior MI (CAT: 25 +/- 6.7%, CK: 739 +/- 263 IU) and in 20 patients with non-Q-wave MI (CAT: 20.7 +/- 1.9%, CK 518 +/- 224 IU). The differences between the groups were significant (p < 0.05). There was a significant linear correlation between CAT and CK in anteroseptal MI (r = 0.57, p < 0.01) and in inferior MI (r = 0.54, p < 0.01), but not in non-Q-wave MI (r = 0.15, p > 0.05). The results are concordant with the hypothesis that thrombotic event contributes more significantly to the pathogenesis of transmural acute myocardial infarction.

[Comparison of amlodipine and the nifedipine retard preparation in the treatment of arterial hypertension]. / Usporedba amlodipina i retard pripravaka nifedipina u lijecenju arterijske hipertenzije.

The efficacy and acceptability of amlodipine (5-10 mg o.d.) and sustained-release nifedipine (20-40 mg b.i.d.) were compared in a multicenter, double-blind clinical trial. After a two-week placebo period, 71 essential hypertensives of both sexes, aged 51.7 +/- 8.5 years, having diastolic blood pressure of 95-114 mmHg were randomly allocated to either amlodipine 5 mg once daily (group A) or nifedipine 20 mg twice daily (group B). With respect to the blood pressure response, the initial dose was doubled after two weeks. No significant differences in blood pressures recorded at baseline and at the end of the placebo period were demonstrated. A significant reduction in both systolic and diastolic blood pressures in the supine position was observed already two days after the start of treatment. In the group A it decreased from 163.2 +/- 21.4/102.7 +/- 8.5 to 155.7 +/- 20.7/98.2 +/- 8.9 mm Hg (p < 0.05) and in the group B from 160.5 +/- 16.2/100.5 +/- 12.2 to 152.2 +/- 17.0/95.4 +/- 9.5 mm Hg (p < 0.05). The similar changes of blood pressure were observed in the standing position, as well. At the end of the study, the overall reduction of the supine diastolic blood pressure was 12.5% in the group A versus 5.2% in the group B (p < 0.05). In the standing position, amlodipine decreased diastolic blood pressure by 8.8% and nifedipine by 6.4% (p < 0.05). Furthermore, amlodipine decreased the standing diastolic blood pressure to a greater extent (8.8% versus 6.4%; p < 0.05) than nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)

[Anterior septal myocardial infarct impairs cardiovascular function more than inferior septal myocardial infarct]. / Anteroseptalni infarkt miokarda vise od inferiornog slabi funkcijsku sposobnost kardiovaskularnog sustava.

The functional ability, expressed as percentage of expected oxygen uptake, measured on the tread-mill according to the Bruce protocol, was assessed in 30 patients with anteroseptal, and in 30 patients with inferior myocardial infarction (MI), 4 months after the incident. In comparison to those with inferior MI, the patients with anteroseptal localization exhibited significantly lower values of functional ability (68.37% +/- 14% versus 75.63% +/- 11%, p < 0.05), significantly higher activities of creatine kinase (CK: 894.7 +/- 441 versus 603 +/- 330 IU, p < 0.01), significantly lower left-ventricular ejection fraction (53% +/- 6.4% versus 58.7% +/- 6.3%, p < 0.01) and higher negative correlation between CK and functional ability (r -0.85 versus r -0.72). In conclusion, anteroseptal infarction is associated with a greater decrease in functional ability then the inferior one, which is partly due to more extensive necrosis with greater deterioration in left ventricular contratility; the mere site of infarction is probably also a contributing factor.

[Orthostatic hypotension. Case report of the Bradbury-Eggleston syndrome]. / Ortostatska hipotenzija. Prikaz slucaja Bradbury-Egglestonova sindroma.

A case of a 71-year-old woman with idiopathic orthostatic hypotension is presented. Several diagnostic procedures which can detect sympathetic pathway lesion are reported. The value of blood pressure measurement and heart rate response to the supine and standing position deep breath, Valsalva maneuver and cold pressor test in differential diagnosis are emphasized. The venoconstriction, venous reflexes and tyramine tests are described, as well. The authors favour an individual therapeutic approach with no limitation of mineralocorticoid dosage. Nonpharmacological measures, such as an increased salt intake, elastic support stockings and swimming are highly recommended.