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Biomedical subjects

L Kovacs

Publications and source records attributed to L Kovacs.

At least 19 recordsLinked to original sources
PubMed1992

Disorders of water balance--hyponatraemia and hypernatraemia.

Plasma sodium concentration depends on water balance, and is normally maintained in a narrow range by an integrated system involving the precise regulation of water intake via thirst mechanism and control of water output via vasopressin secretion. Anything that interferes with the full expression of either osmoregulatory function exposes the patient to the hazards of abnormal decreases or increases in plasma sodium level. Hyponatraemia is almost always due to a defect in water excretion. Increased intake may contribute to the problem but is rarely, if ever, a sufficient cause. Hypernatraemia is almost always due to deficient water intake; excessive water losses may contribute to the problem, but they are never a sufficient cause. The most dangerous and usually the most blatant clinical effects of the disturbed water balance are those involving the central nervous system. Complex adaptive mechanisms have been developed to mitigate the impact of both hypo- and hypernatraemia on brain cells. However, the same protective changes render the brain more susceptible to severe neuropathology that may arise from inappropriate treatment of these disorders.

Diagnosis, Differential↗
PubMed1992

Syndrome of inappropriate antidiuresis.

Since it was first recognized 35 years ago, the syndrome of inappropriate antidiuretic hormone (SIADH) secretion has become the most commonly recognized cause of hyponatremia among hospitalized patients. The syndrome is caused by excessive intake of fluids when urinary dilution is impaired by physiologically inappropriate secretion or administration of vasopressin or other antidiuretic hormones. Inappropriate secretion of the hormone may be ectopic by a malignancy or ectopic and can ensure from any of three different types of osmoregulatory defects. Rarely, there is no demonstrable defect in the osmoregulation of vasopressin. The excessive fluid intake may be due to inappropriate thirst but often is iatrogenic. The syndrome occurs in association with many diseases, particularly of the lungs and brain, and can also be caused by drugs or surgery. Its principal symptoms are neurologic and due to the associated hypo-osmolality of body fluids. Diagnosis requires exclusion of certain other hormonal or hemodynamic disorders that can also increase vasopressin or impair urinary dilution. Therapy differs depending on the severity and duration of the hyponatremia but is always based on cautiously raising plasma sodium by fluid restriction, infusion of hypertonic saline, or administration of drugs that block the antidiuretic effect of vasopressin.

Arginine Vasopressin↗
PubMed1991

[The advantage of preventive vaginal antisepsis with hexetidine in obstetrics and gynecology].

In five studies, the advantage of repeated vaginal prophylaxis by a new preparation of hexetidine vaginal suppositories (10 mg) was investigated prospectively, randomised and method-controlled (n = 2 x 50). After a five-day application, the hexetidine group achieved bacterial reductions of five log CFU/ml in the vagina and nearly three log CFU/ml in the cervix uteri, whilst no reduction was found in the controls at any time (p less than 0.01). The reduction of individual bacterial species was investigated in 224 pregnant and also gynaecological patients. In cases of impending preterm childbirth, a five-day application of 20 mg hexetidine/day could reduce all bacteria sufficiently with the exception of lactobacilli; especially beta Streptococci were reduced. The same was achieved by a three-day application of 10 mg hexetidine/day pre-operatively. A long-term study in 11,724 deliveries showed, that neonatal infectious mortality and morbidity after 36 gestational weeks could be reduced significantly by hexetidine. The new hexetidine preparation appeared to be efficient in vaginal antisepsis, especially in pregnancy. A favourable lactobacilli-selective effect was demonstrated. Since the importance of lactobacilli in vaginal ecology is known, hexetidine prophylaxis must be considered as advantageous in Obstetrics and Gynecology. From a practical and economic point of view, the application of hexetidine as vaginal suppositories appears favourable compared to antiseptic solutions.

Adult↗
PubMed1991

Decline of myoplasmic Ca2+, recovery of calcium release and sarcoplasmic Ca2+ pump properties in frog skeletal muscle.

1. The two calcium indicators Antipyrylazo III (AP III) and Fura-2 were used simultaneously to monitor free myoplasmic [Ca2+] in voltage-clamped cut segments of frog skeletal muscle fibres (8-10 degrees C). Antipyrylazo III was used for the relatively large [Ca2+] transients during 100-200 ms depolarizing pulses to -20 to 0 mV and for the rapid decline of [Ca2+] during the 200 ms after the pulses. Fura-2 was used to follow the slow decline of the small remaining elevation of [Ca2+] during the following 16 s (slow recovery period) and to monitor resting [Ca2+]. 2. From 1 to 16 s of the slow recovery period [Ca2+] declined with two exponential components, having time constants of 1.9 +/- 0.3 and 13.5 +/- 1.5 s (these and all other values are means +/- S.E.M. of eleven runs from seven fibres). At 1.2 s after the end of the pulses the amplitudes of the fast and slow exponential components of decline of [Ca2+] were 34 +/- 7 and 31 +/- 4 nM, respectively. The resting [Ca2+] in these runs was 40 +/- 4 nM. 3. The time course of calcium bound to parvalbumin [( Ca-Parv]) was calculated from the [Ca2+] records using literature values for the parvalbumin kinetic constants. From 1 to 16 s of the slow recovery period the total calcium [Ca]T outside the sarcoplasmic reticulum (SR) was assumed to equal [Ca-Parv] + [Ca-Fura]. During this period [Ca]T declined with two exponential components having time constants of 1.7 +/- 0.2 and 14.2 +/- 1.4 s, the same as those for [Ca2+]. Assuming the total concentration of parvalbumin cation binding sites to be 1000 microM, the fast and slow components of [Ca]T had amplitudes of 117 +/- 21 and 147 +/- 16 microM, respectively, at 1.2 s after the pulses. 4. The rate of decline of [Ca]T, -d[Ca]T/dt, was used as a measure of the net rate of removal of calcium from the myoplasm by the SR. From 3 to 16 s of the slow recovery period and in the resting fibre -d[Ca]T/dt varied with [Ca2+] according to A[Ca2+]n-L. The term A[Ca2+]n represents the pump rate and L represents a constant rate of calcium leak from the SR. 5. For 40 nM less than or equal to [Ca2+] less than or equal to 80 nM, the power n for the [Ca2+] dependence of pump rate was 3.9 +/- 0.6.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Effect of oral prostaglandin E2 on uterine contractility and outcome of treatment in women receiving RU 486 (mifepristone) for termination of early pregnancy.

It has been shown that the antiprogestin RU 486 (mifepristone) increases the sensitivity of the early pregnant human uterus to the stimulatory action of synthetic prostaglandin E (PGE) analogues. To examine if RU 486 also increases uterine sensitivity to the naturally occurring PGE2 given orally, two investigative approaches were used in the present studies: (i) direct registration of uterine contractions before and after PGE2 administration in untreated and RU 486-treated early pregnant women; and (ii) a double-blind, randomized, controlled efficacy trial involving treatment of pregnant women (amenorrhoea of less than or equal to 49 days) with RU 486 (25 mg twice daily for 4 days) and PGE2 (1 mg once or twice) or placebo on the last day of RU 486 treatment. The results indicate that oral PGE2 at the doses employed had little or no stimulatory effect on uterine contractility and that it did not improve the rate of complete abortion achieved with RU 486 alone. Overall, 25 of 42 women (59%) had a complete abortion, 15 women (36%) did not abort and the remaining two had incomplete abortions. Women with complete abortions had significantly lower pretreatment levels of progesterone and a longer duration of induced bleeding than those who did not abort. Thus oral PGE2, when given in clinically acceptable doses, is not a suitable alternative to synthetic PGE analogues for use in combination with RU 486 for termination of early pregnancy.

Abortifacient Agents↗
PubMed1989

Termination of early human pregnancy with RU 486 (mifepristone) and the prostaglandin analogue sulprostone: a multi-centre, randomized comparison between two treatment regimens.

A multi-centre, randomized trial was conducted to compare the efficacy and side-effects of two combination regimens of the antiprogestin RU 486 and the intramuscular PGE2 analogue sulprostone for termination of early pregnancy (amenorrhoea up to 49 days). Women in the 3-day group (n = 125) received 25 mg RU 486 twice daily for 3 days plus a single injection of 0.25 mg sulprostone in the morning of the third day of antiprogestin treatment. In the 4-day group (n = 126), RU 486 was given for 4 days and the sulprostone injection in the morning of the fourth day. Treatment outcome in the two groups was similar. Overall, 88.8% had a complete abortion, 6.8% an incomplete abortion and 2.4% were treatment failures; in the remaining 2% treatment outcome could not be determined. Only three of the six women with treatment failure still had detectable fetal heart activity when the pregnancy was terminated by vacuum aspiration two weeks after the start of treatment. Five of the 17 interventions for incomplete abortion were carried out as emergency procedures because of heavy bleeding; two of these five women were given a blood transfusion. The majority of the curettages (10/17) were performed in one centre. If the data from this centre and the women with undetermined treatment outcome were excluded, the rates for complete abortion, incomplete abortion and treatment failure in the remaining six centres were 93.6, 3.7 and 2.7%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents↗
PubMed1989

Alteration of lymphocyte reactivity in pregnant women treated with the progesterone receptor inhibitor ZK 98734.

Thirteen women during the 5th and 6th weeks of gestation were treated with a progesterone receptor blocker (ZK 98734) for pregnancy termination. Five patients received 100 mg/day of the compound, and eight patients received 50 mg/day for 4 days. Daily blood samples were obtained during the treatment period as well as on days 8 and 15 after the beginning of drug administration, and cytotoxic activity, progesterone sensitivity, and progesterone binding capacity of the lymphocytes were determined. Determination of SP-1 concentrations monitored the saturation state of trophoblastic progesterone receptors. High and low responders to the progesterone antagonist were identified. Lymphocytes of high responders treated with the 100 mg/day dose demonstrated a rapid increase of cytotoxicity, with a concomitant fall in progesterone sensitivity and progesterone binding capacity. Vaginal bleeding began as early as the 2nd day of treatment, and pregnancy was terminated by the 8th day of the treatment. Low responders receiving 100 mg/day demonstrated similar but attenuated changes. Low responders did not bleed during the first 4 days of treatment, and termination of pregnancy occurred later compared to high responders. Lymphocytes of high responders treated with 50 mg/day behaved similarly to those obtained from the low responders treated with 100 mg/day, and abortion was not completed before the 25th day after the beginning of the treatment. Lymphocytes function of low responders treated with 50 mg/day did not change significantly, the SP-1 concentration did not decline, and pregnancies continued. We conclude that a difference in sensitivity to the progesterone receptor blocker explains the selective block at trophoblastic binding sites only and the inability to block those in the lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortifacient Agents↗
PubMed1988

Differential effects of tetracaine on charge movements and Ca2+ signals in frog skeletal muscle.

The effects of tetracaine on charge movements and on antipyrylazo III signals monitoring intracellular delta [Ca2+] were compared in cut frog semitendinosus muscle fibers in a single vaseline gap-voltage clamp. Low tetracaine concentrations (25-40 microM) markedly reduced delta [Ca2+] signals and shifted the rheobase. However, they neither influenced charge movement nor that peak delta [Ca2+] value associated with the contractile threshold. Higher tetracaine concentrations (100-200 microM) partly inhibited charge movements in cut fibers. They separated a steeply voltage-sensitive charge, some of whose features resembled 'q gamma' reported in intact fibers, and whose movement preceded delta [Ca2+] signals at threshold. These findings: (a) directly confirm an earlier suggestion that tetracaine acts on steps in excitation-contraction coupling rather than myofilament activation; (b) show that tetracaine at low concentrations can directly interfere with sarcoplasmic reticular calcium release without modifying charge movement; (c) show that the tetracaine-sensitive charge, first found in intact fibers, also exists in cut fibers; and (d) make it unlikely that tetracaine-sensitive charge transfer is a consequence of Ca2+ release as suggested on earlier occasions.

Animals↗
PubMed1987

A multicentered pharmacokinetic, pharmacodynamic study of once-a-month injectable contraceptives. I. Different doses of HRP112 and of DepoProvera. World Health Organization Task Force on Long-acting Systemic Agents for Fertility Regulation.

A multicentered study was undertaken at three institutions in Hungary, Mexico and Thailand in women of reproductive age to evaluate the effects of full and half doses of HRP112 (depot-medroxyprogesterone acetate (DMPA) plus estradiol cypionate) and DMPA alone on ovarian function, bleeding patterns and HDL-cholesterol levels. Full dose HRP112 contained 25mg DMPA plus 5mg, of estradiol cypionate and the half dose, 12.5mg DMPA plus 2.5mg of estradiol cypionate. The full and half dose DMPA were 25 and 12.5mg respectively. In all, 88 women were recruited in the study and randomized within each centre, to the four treatment groups. Subjects were studied for a control cycle, three one-month injection intervals and followed-up for a further two months. Serum concentrations of estradiol, progesterone and medroxyprogesterone acetate were determined three times a week during the third injection interval and during the two months of follow-up. While the results from all centres indicated that the four preparations were all effective in inhibiting ovulation for at least one month, there were marked between centre differences in pharmacokinetic profiles. More regular bleeding patterns were observed in women who received the estrogen-progestogen combination preparations than in those who received DMPA alone.

Adolescent↗
PubMed1986

The effect of the contraceptive pill on blood pressure: a randomized controlled trial of three progestogen-oestrogen combinations in Szeged, Hungary.

As part of an international multicentered investigation a double-blind comparative clinical trial was conducted at the Department of Obstetrics and Gynecology, University Medical School, Szeged, Hungary, in order to study the effect of different combined oral contraceptives on blood pressure. Healthy, normotensive women were randomly allocated to either of the following oral contraceptives: 250 micrograms levonorgestrel + 50 micrograms ethinyloestradiol (LN 250 + EE 50), 250 micrograms levonorgestrel + 30 micrograms ethinyloestradiol (LN 250 + EE 30), 1 mg norethisterone acetate + 50 micrograms ethinyloestradiol (NA 1 + EE 50). Standardized blood pressure measurements were carried out at admission and 3, 6, 9, and 12 months after admission. Blood pressure change from admission to subsequent visits was analysed in subjects who were seen by the same observer both at admission and the follow-up under consideration. The systolic blood pressure slightly but not significantly increased in groups LN 250 + EE 50 and NA 1 + EE 50, whereas the diastolic pressure showed a minimal decrease. In group LN 250 + EE 30 both systolic and diastolic blood pressure increased significantly (+5.58 and +3.20 mm Hg, respectively) at the 12-month follow-up. The study supports previous findings that combined oral contraceptive use is associated with a moderate rise in blood pressure. The progestogen-to-oestrogen ratio in the pill may be as important in this context as the dose of either component itself.

Adolescent↗
PubMed1975

Dynamic evaluation of growth hormone (GH) and prolactin (hPRL) secretion in active acromegaly with high and low GH output.

Ten patients with active acromegaly were studied. In 9 plasma GH levels failed to suppress after glucose (OGTT), in 8 an increase in serum GH occurred after thyrotropin releasing hormone (TRH). After L-Dopa, 4 patients showed no change in serum GH, 3 exhibited a decrease and in 3 an increase in serum hGH occurred. With a combined insulin (ITT) and arginine (ATT) test, 2 patients exhibited an increase in hGH, and in 6 no change occurred. Fasting serum GH concentration was less than 11 ng/ml in 5 patients. Basal prolactin (hPRL) levels were normal in all patients including two with galactorrhea. L-Dopa suppressed and TRH stimulated hPRL secretion in all, but the responses which were seen were subnormal. Hydrocortisone infusion in two acromegalics did not affect the prolactin induced increase after TRH but blunted the GH increase after TRH.

Acromegaly↗