Biomedical subjects
M Gajdos
Publications and source records attributed to M Gajdos.
Serum ex vivo lipoprotein oxidizability in patients with ischemic heart disease supplemented with vitamin E.
The decreased oxidizability of plasma lipoproteins is related to the increased vitamin E intake and its association with a relatively lower incidence of coronary heart disease has been proposed. We investigated the effect of the in vivo vitamin E supplementation on the oxidizability of serum lipids in patients with ischemic heart disease and a moderate hypercholesterolemia. Thirty-two patients (16 males and 16 postmenopausal women) participated in this placebo-controlled, randomized trial. They were treated with 400 mg vitamin E/day for 6 weeks. The copper-induced serum lipid oxidizability ex vivo was assessed by measuring conjugated diene formation at 245 nm. We also measured vitamin E, malondialdehyde (MDA) and uric acid concentrations in the plasma. Because of observed significant differences in parameters of serum lipid oxidizability (lag time and maximal rate of oxidation), plasma alpha-tocopherol and MDA levels between male patients and postmenopausal women supplemented with vitamin E, the results were compared between both genders. Six weeks of vitamin E supplementation significantly increased plasma vitamin E levels (by 87 %) in male patients but in postmenopausal women only by 34 %. Concomitantly with increased plasma levels of vitamin E the decrease in plasma MDA levels was observed in male patients (decrease by 20 %; p=0.008), but in postmenopausal women the decrease did not attain statistical significance. Plasma uric acid levels were not apparently changed in placebo or vitamin E supplemented groups of patients. The changes in ex vivo serum lipid oxidizability after vitamin E, supplementation have shown a significantly prolonged lag time (by 11 %; p=0.048) and lowered rate of lipid oxidation (by 21 %; p=0.004) in male patients in comparison with postmenopausal women. Linear regression analysis revealed a significant correlation between plasma vitamin E levels and the lag time (r=0.77; p=0.03) and the maximal rate of serum lipid oxidation (r=-0.70; p=0.05) in male patients. However, in postmenopausal women the correlations were not significant. We conclude that 400 mg vitamin E/day supplementation in patients with ischemic heart disease and a moderate hypercholesterolemia influenced favorably ex vivo serum lipid oxidation of male patients when compared with postmenopausal women. The observed differences between both genders could be useful in the selection of the effective vitamin E doses in the prevention of coronary heart disease.
Ciprofibrate increases plasma concentration of platelet-derived growth factor AB in patients with advanced atherosclerosis and hyperlipidemia independently of its hypolipidemic effects.
Fibrates, besides their hypolipidemic action, share alternative effects, such as decreased plasma fibrinogen and uric acid levels. Because of their complex action, additional effects have been investigated. A group of 23 patients with clinical signs of atherosclerosis and hyperlipoproteinemia was randomly allocated after a 1-month washout period and treated with either 100 mg/d of ciprofibrate or 100 mg/d of aspirin for 2 months. Patients were then treated with a combination of these two agents for the next 2 months. Ciprofibrate decreased plasma concentrations of triglycerides (-29%) and very-low-density lipoprotein cholesterol (-27%) in monotherapy and a larger reduction was observed if ciprofibrate was added to the aspirin therapy: triglycerides (-39%), very-low-density lipoprotein cholesterol (-33%), total cholesterol (-18%), low-density lipoprotein cholesterol (-17%), and increased high-density lipoprotein cholesterol (+36%). Ciprofibrate increased plasma levels of platelet-derived growth factor (PDGF) AB in both monotherapy patients (+162.9 pg/ml, +297%) and in aspirin-pretreated patients (+129.8 pg/ml, +134%); the increase of PDGF AB platelet store was significant only in aspirin-pretreated patients (+11.1 ng/ml, +51%). Aspirin in monotherapy did not modulate either plasma or platelet store of PDGF AB. Ciprofibrate did not inhibit thromboxane B 2 synthesis in platelets. Aspirin did not influence plasma thromboxane B 2 concentration at all, whereas it decreased thromboxane B 2 platelet production markedly in monotherapy (-85%) and in combination with ciprofibrate (-91%). Ciprofibrate increases PDGF AB content, which is amplified by aspirin pretreatment without correlation with its hypolipidemic action. The increase of PDGF production is suggested to participate in plaque stabilization.
Enalapril inhibits growth and proliferation of various tissues in rat normotensive four-sixths kidney ablation nephropathy.
Most experimental studies on kidney proliferation and its attenuation by angiotensin-converting enzyme inhibitors were performed in the rat hypertensive remnant-kidney model with a five-sixths kidney ablation. The developing hypertension rose the objections on the hypertension and its treatment in control rats. A normotensive four-sixths remnant-kidney model (Nx) was elaborated, compared with sham-operated (S) animals, and a subantihypertensive dosage of enalapril (E) was administered for 4 weeks of intensive kidney tissue proliferation (NxE). The pair-fed groups increased their body weight and blood pressure comparably. Moderately increased plasma creatinine and urea concentrations were found in the Nx group; markedly increased levels in the NxE group. Nx increased proteinuria, and E attenuated its increase. The remnant-kidney weight (Nx 912+/-31 vs. S 1,111+/-36 mg, p<0.001) was still lower, but collagen (Col; Nx 164+/-2 vs. S 148+/-5 mg/100 g, p<0.05) and tubular protein/DNA ratio (Nx 26.2+/-10.8 vs. S 9.8+/-1. 0, p<0.05) increased markedly in the Nx group; E attenuated the kidney growth (NxE 719+/-31 vs. Nx 912+/-31 mg, p<0.01) and decreased the tubular protein/DNA ratio remarkably (NxE 15.3+/-10.5 vs. Nx 26.2 +/-10.8), but E did not inhibit the Col accumulation. Nx decreased the heart (Nx 1,002+/-28 vs. S 1,130+/-41 mg, p<0.05), but not liver weights and did not influence Col concentrations or protein/DNA ratios either in heart or liver. E potentiated the weight decrease of heart (NxE 862+/-20 vs. Nx 1,002+/-28 mg, p<0.01) and liver (NxE 8.3+/-0.44 vs. Nx 10.3+/-0.51 g, p<0.001) and Col accumulation (heart: NxE 113+/-6 vs. Nx 92+/-5 mg/100 g, p<0.01; liver: NxE 134+/-8 vs. Nx 101+/-9 mg/100 g, p<0.01). Nx did not influence either the soleus muscle weight or its Col accumulation, but it increased its protein/DNA ratio (Nx 66.3+/-4.7 vs. S 35.5+/-2. 8 mg/100 g, p<0.01). E increased the Col concentration in muscle (NxE 141+/-3 vs. Nx 110+/-5 mg/100 g, p<0.01), while it attenuated the increase in protein/DNA ratio (NxE 36.6+/-2.1 vs. Nx 66.3+/-4.7, p<0.01). In conclusion, kidney ablation nephropathy stimulating kidney proliferation evokes only minor changes in heart, liver and striated muscle. E inhibits markedly the kidney proliferation and functional recovery, but does not prevent the Col accumulation. E evokes antiproliferative changes also in the heart and surprisingly even in the liver. Alterations in soleus muscle are only borderline.
[The effect of monotherapy with ciprofibrate and in combination with acetylsalicylic acid on the spectrum of lipids, thromboxane and fibrinogen in patients with atherosclerosis and hyperlipoproteinemia].
Ciprofibrate is one of the basic drugs used to lower risk values of lipid parameters and fibrinogen in atherosclerosis patients. Since antiaggregation treatment with acetylsalicylic acid is a complex part of obligatory therapy of these patients, the authors studied the influence of ciprofibrate on chosen lipid parameters, fibrinogen and thromboxane in monotherapy, and also in combination with acetylsalicylic acid (ASA) in patients with advanced atherosclerosis and hyperlipoproteinemia. In the first group of patients (A-C, n = 12) after one month of low-lipid diet acetylsalicylic acid in a dose of 100 mg was administered daily during a period of 2 months followed by addition of 100 mg of ciprofabrate daily during the next 2 months. In the second group of patients (C-A, n = 11) after one month of low-lipid diet the same drugs were administered but in opposite order. Ciprofibrate was most effective in lowering the levels of triacylglycerids (-41%) and VLDL-cholesterol (-34%), but effectively lowered also the values of total cholesterol and LDL-cholesterol. In both studied groups it led to mild increase of HDL-cholesterol levels. Simultaneous administration of ASA did not significantly influence its hypolipemic activity. Ciprofibrate also significantly lowered the level of fibrinogen (-17%). Increase of the total number of platelets by about 10% was not accompanied by changes of the values and production of thromboxane. Simultaneous administration of ASA caused more than 90% inhibition of thromboxane production in monotherapy and in combination with ciprofibrate. Ciprofibrate is an effective hypolipidemic agent, also lowering the level of fibrinogen. Its combination with ASA is adequate, safe and without negative interaction influencing treatment. (Tab. 6, Fig. 1, Ref. 16.)
Effective long-term inhibition of thromboxane production but not of serotonin release in patients with coronary heart disease by 30 mg/d acetylsalicylic acid dosage.
Efficacy of aspirin (Acetylsalicylic acid, ASA) antiaggregatory prevention was demonstrated in a series of clinical trials. The recommended ASA doses decreased gradually and doses 50-30 mg ASA/d are intensively studied at the present time. A group of 42 patients with coronary heart disease was evaluated: (1) Basal TXB2 production during spontaneous blood clotting was 360 +/- 37.6 ng/ml; (2) Two initial doses were tested: while 200 mg ASA inhibited, during spontaneous blood clotting, median TXB2 production by 99.9% (serum TXB2 concentration 1.35 ng/ml), 30 mg ASA median inhibition was just 42.0% (serum TXB2 151 ng/ml); (3) 30 mg ASA/d maintenance dose was evaluated for 3 months. The median TXB2 production inhibition was 98.5% (serum TXB2 3.75 ng/ml, first month) and 94.0% (serum TXB2 14.2 ng/ml, third month); (4) Four patients did not respond sufficiently, because of noncompliance verified by the determination of salicyluric acid urinary excretion, the lower limit of excretion being <3 micromol/2 h; (5) Both initial and maintenance ASA dose decreased metabolic TXA2 endproducts in urine; (6) 5HT platelet release did not decrease; (7) Potential changes of 5HT metabolic elimination were excluded by the simultaneous determination of 5-hydroxyindoleacetic acid (5HIAA). In conclusion, 200 mg initial dose and 30 mg ASA/d maintenance dose are suggested to be maximally inhibitory for TXB2 production without influence on 5HT release.
[Brain injuries with abattoir guns].
The authors present a report on the treatment of 16 patients with brain injuries caused by a slaughterhouse gun. Nine patients had to be re-operated because of the presence of a foreign body; the primary operations of six patients were made in another surgical department. Two patients were re-operated twice. The reason for the first revision were bone fragments. The reason for the second revision was nasal liquorrhoea and posttraumatic hydrocephalus. Three patients (18.75%) of the investigated group died. The immediate cause of death was cerebral oedema. Eleven patients (68.75%) were referred for after-treatment to other health facilities, their condition had already improved. Two patients (12.5%) were referred in a poor, unaltered condition (coma). The rare incidence of gunshot injuries leads to a certain embarrassment how to treat patients with this type of injury. It was found that in gunshot wounds of the head and brain it is necessary to revise the gunshot canal from a craniotoic approach, remove foreign bodies, bone fragments, brain debris and then close perfectly the aperture in the dura mater, remove the margins of the bone contaminated with the injuring object and suture the skin. The authors draw attention to difficulties associated with localisation of the foreign body in the gunshot canal and possibilities of peroperative application of two-dimensional ultrasonography.
[Prevention and therapy of atherosclerosis].
Atherosclerosis is a complex progressive process with high morbidity and frequent dramatic mortality. The experience from the developed countries justifies the effectiveness of atherosclerosis prevention. The combination of nonpharmacologic, antiaggregatory and antihyperlipemic prevention reaches currently the effectiveness of surgical intervention, with the exception of sudden events. On the other hand the surgical intervention does not restore the process of atherosclerosis and requires the same secondary prevention if the long term prognosis is to be improved. The review presents the guidelines on nonpharmacologic, antihyperlipemic (up to the combination of statin with fibrates) and the antiaggregatory prevention with the initial dose of ASA being 200 mg and a long term dose being > or = 30 mg of ASA/d treatment. (Tab. 4, Fig. 3, Ref. 25.)
Effects of angiotensin-converting enzyme inhibitors on glucose and lipid metabolism in essential hypertension.
Data of 52 patients, 29 women and 23 men aged 32-68 years (mean age 47 years) with essential hypertension, participating in three open therapeutic trials with either enalapril, lisinopril, or perindopril were evaluated to assess the effects of angiotensin-converting enzyme (ACE) inhibition on glucose and lipid metabolism. The 75-g oral glucose tolerance test (oGTT) was performed, and plasma glucose and insulin levels, as well as total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides levels were determined before and after the 8- to 12-week treatment. Minor differences in the blood pressure (BP)-lowering effect and metabolic response were obtained with the ACE inhibitors studied; only lisinopril improved glucose tolerance significantly; blood lipids were not changed by any drug. The entire patient population showed only a slight reduction in 1-h postload glucose after treatment. More obvious improvement in glucose tolerance was evident in hypertensive patients who were glucose intolerant and/or insulin resistant (GI/IR, 53.8% of all), however. This subgroup also showed a slight but not significant increase in HDL-cholesterol and a decrease in triglycerides levels. Only a slight change or no change in plasma glucose, insulin, and lipid values was noted in hypertensive patients with normal glucose tolerance (NGT) and insulin sensitivity. These favorable effects were expressed only after ACE inhibitor monotherapy, but not when hydrochlorothiazide was added. The results indicate that a lack of stratification of hypertensive patients with regard to glucose tolerance or insulin sensitivity could be a confounding factor in evaluation of metabolic effects of ACE inhibitors.
[Prevention of progression in nephropathies].
Intermittent dialysis is excessively expensive and pretentious psychologically and socially. As a result the research is concentrated on the prevention of kidney disease progression. Preventive measures: a) Protein restriction forms the basis of nonpharmacologic measures. b) Consequent antihypertensive therapy, with the aim to decrease blood pressure < 17.5/11.25 kPa (140/90 Torr), is the most effective prevention. The basic drugs are ACEI eventually in combination with Ca antagonists. They even reverse kidney disease progression in early phases. c) Antiaggregation therapy prevents the formation of fibrin deposits in glomeruli and the thrombogenesis. d) Insulin resistance correction prevents the development of glomerulosclerosis and atherosclerosis. e) Antihyperlipemic therapy is required only in a small number of patients. f) Correction of mineral balance prevents or corrects osteodystrophy. These measures could decrease kidney disease progression and the entrance of patients into intermittent dialysis by 10-20% and a further decrease to 50% is expected to be reached until the year 2000. (Fig. 3, Tab. 3, Ref. 43.).
[Lisinopril in the monotherapy of patients with essential hypertension: the effect of therapy on glucose and lipid metabolism].
Twenty patients with mild or medium severe essential hypertension were treated with lisinopril (Prinivil), 20 or 40 mg resp. by the oral route per day. After six weeks of treatment the mean values of systolic pressure declined from 169 +/- 4.38 mm Hg to 149 +/- 3.96 mm Hg and the diastolic pressure from 108 +/- 0.99 mm Hg to 91 +/- 1.77 mm Hg. The differences were statistically significant. In 40% of the patients it was necessary to increase the daily dose of lisinopril to 40 mg. When this was used, the mean values of systolic pressure declined to 140 +/- 3.18 mm Hg and those of diastolic pressure declined to 85 +/- 1.43 mm Hg during the subsequent six weeks. The blood pressure of all investigated patients was within the range of reference values. The authors recorded a positive effect on the glucose metabolism in particular in patients with impaired glucose tolerance. The mean blood sugar levels during the second hour following glucose administration during the oGTT declined from 9.81 +/- 0.54 mmol/l before treatment to 7.28 +/- 0.79 mmol/l after 12 weeks of lisinopril treatment. The values of immunoreactive insulin after the mentioned intervals declined from 82.49 +/- 5.6 to 34.94 +/- 8.37 microM/ml. The investigated parameters of the lipid spectrum did not change after 12 weeks of treatment. The authors did not observe any marked side-effects of treatment.
The use of a nonlinear absorption model in the study of ascorbic acid bioavailability in man.
A two-compartment disposition model of ascorbic acid (AA) pharmacokinetics with saturable and time-constrained intestinal absorption was developed. The model was fitted to pharmacokinetic data obtained after oral administration to nine healthy volunteers of two effervescent dosage forms differing in AA content: Celaskon 60 mg (CK60) and Celaskon 500 mg (CK500). It was demonstrated that in the case of CK500 less than 30% of the dose was absorbed as compared with CK60. Parameters of the AA nonlinear absorption kinetics were assessed by simultaneous fitting of mean concentration-time data for both doses and placebo. The relatively short duration of absorption found (3.2 h) can explain the failure of past attempts to increase the AA bioavailability using sustained-release dosage forms. Model simulation showed that the ingestion of 60 mg with 3-4 h intervals is optimal for maximal bioavailability of AA.
[A brain injury caused by a fragment from a soda water carbon dioxide cartridge].
The authors present a report on the treatment of a female patient with a brain injury caused by a splint from an exploded sparklet used for making soda water. The rare occurrence of gunshot wounds in peace time leads to embarrassment as regards treatment of patients with this type of injury. It was found that in gunshot wounds of the head and brain it is necessary to revise the pathway of the splint after craniotomy, remove the foreign body, bone fragments and debris, then close carefully the opening in the dura mater, remove the margins of the bone contaminated with the object which caused the injury and stitch the skin. The authors draw attention to difficulties associated with localization of the foreign body in the pathway of the splint and to the possible use of peroperative two-dimensional ultrasonography.
[The effect of dipyridamole on hippurate excretion in healthy volunteers and in patients with renal insufficiency].
Organic anions retained in patients with renal failure participate in a substantial way in the metabolic acidosis and thus also the catabolism in renal failure. The basic disorder is the reduced capacity of the transport system of organic ions. Therefore drugs are sought to enhance its activity. Acute investigation of healthy volunteers revealed that 150 mg dipyridamol increased the urinary hippurate excretion, while the serum hippurate concentration declined. In patients with renal failure there is the same tendency, though less marked, and due to the variability of functions of individual patients this trend is insignificant. It is assumed that this hitherto not described action of dipyridamol may be of therapeutic importance when administered to patients with impaired renal function.
Serum hippurate and its excretion in conservatively treated and dialysed patients with chronic renal failure.
54 healthy volunteers or patients with normal kidney and liver function, 17 patients with decreased kidney function and 12 dialysed patients were evaluated for their serum hippurate accumulation and kidney excretion. It was found that there was an inverse relationship between serum hippurate and the clearance of endogenous creatinine (CCr) and a free relationship between fractional excretion of hippurate and CCr. The excretory capacity in residual nephrons was increased. This was caused by the greater glomerular filtration load which increased up to 25 times and tubular secretion which increased 7 times in dialysed patients. The relative contribution of glomerular filtration to hippurate excretion rose from about 20% in controls to almost 50% in dialysed patients. True kidney adaptation was localized in the organic anion transport system of proximal tubules.
[Hemophilia from the viewpoint of the neurosurgeon].
The authors describe a case of cerebral haemorrhage associated with haemophilia A--their own observation, findings and confrontation with data in the literature. They draw attention to the rare incidence of the above complication, discuss the site of haemorrhage and possibilities of treatment.
[Pefloxacin in the treatment of recurrent urinary tract infections].
Thirty-seven patients with relapsing infections of the urinary tract were treated with pefloxacine, 400 mg/12 h for a period of 7-28 days. The clinical success of treatment was 100%, the bacteriological success 95%. Within 3-4 weeks after termination of treatment 63% of the patients did not develop a relapse, in particular those who did not have morphological changes of the kidneys. Side-effects-gastrointestinal, nervous, dermatological--during treatment were not severe. The results are comparable with results of the effect of ofloxacine in a similar group of patients.
[Pharmacokinetic modeling in clinical practice: pefloxacin].
Pharmacokinetic modelling allows to set up a therapeutic plan for administering a drug. The advances of this procedure are particularly remarkable in drugs discharged by the liver. The principles of this approach are presented and illustrated on the treatment with pefloxacin. The potential causes of the adverse effect of the drug observed in one patient of the series studied could thus be suggested.