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Biomedical subjects

L Varga

Publications and source records attributed to L Varga.

At least 19 recordsLinked to original sources

[Treatment of carcinoid syndrome with a somatostatin analogue].

Octreotide, a long-acting somatostatin analogue has recently been introduced in the therapy of gastroenteropancreatic endocrine tumors, but home experience has been lacking. With the aim of drawing attention to this therapeutic possibility, a case of malignant carcinoid syndrome treated with octreotide for 18 months is reported. Despite the therapeutic attempts preceding the octreotide administration a gradual progression in clinical symptoms was observed and cardiac failure due to fibrotic and valvular heart disease developed. Cytotoxic chemotherapy, serotonin antagonists or repeated selective embolisation of the hepatic artery only resulted in a short transitional improvement. Octreotide in a dose of 100 micrograms three times daily by subcutaneous injection provided effective and rapid relief from episodic flushing and serious diarrhoea. Plasma level of serotonin and 24-hour urinary excretion of 5-hydroxyindolacetic acid decreased from 6 micrograms/ml to 2 micrograms/ml and from 800 mumol/day to 70 mumol/day, respectively. No changes in the number and extension of liver metastases could be seen after introducing the octreotide treatment. The patient's compensated cardiac status could be preserved and continuous therapy provided an acceptable quality of life.

Humans

[Helicobacter pylori allergy].

A case of a 44 year old woman with antrum gastritis and H. pylori infection was reported. After unsuccessful treatment of the disorder with bismuth and tinidazole, an auto-vaccine was prepared from the bacterium in order to eliminate the infection. After the first injection of the vaccine a generalised urticaria was observed. In the development of the skin eruptions a type I, and a type IV allergic reaction could be demonstrated using the H. pylori specific RAST-test and leukocyte migration inhibition respectively. After eradication of the bacterium by amoxycillin treatment, the clinical signs of both the gastrointestinal and allergic diseases disappeared.

Adult

Effect of acute and chronic acid suppression on plasma gastrin release in the rat.

The mechanisms by which administration of the H+,K(+)-ATPase inhibitor B 831-78 or intragastric perfusion with NaHCO3 induces plasma gastrin release were studied in the rat. Experiments were performed after a washout of residual intragastric contents in fasted animals provided with chronic gastric fistulae. Acute and chronic administration of B 831-78 elevated plasma gastrin dose-dependently up to 5-6 times above control levels, while the increase was only twofold with intragastric NaHCO3 infusion despite similar neutralization of gastric acidity. The profound hypergastrinaemia induced by the H+,K(+)-ATPase inhibitor, after both acute and chronic treatment, was completely prevented or reversed by intragastric perfusion with physiological amounts of acid (0.15 N HCl, 2.5 ml/h). The hypergastrinaemia was, however, largely resistant to high doses of atropine (4.3 mumol/kg) and of the M1 selective muscarinic antagonist telenzepine (10 mumol/kg). In contrast, the modest increase in plasma gastrin induced by gastric perfusion with NaHCO3 was completely suppressed by the high atropine dose and was attenuated by small doses of atropine or telenzepine (0.01 mumol/kg and 1 mumol/kg). These results demonstrate that, in the rat, blockade of the H+,K(+)-ATPase can potently induce gastrin release in the absence of a meal. Moreover, they suggest that interruption of the negative feedback between acid and gastrin release is the main mechanism through which this class of drugs releases gastrin in the rat. Since a similar degree of gastrin release cannot be achieved by alkalinization of gastric contents, additional hormonal or neural regulatory factors may contribute to the drug-induced hypergastrinaemia.

Adenosine Triphosphatases

Interaction of liquid aluminium phosphate and aluminium hydroxide with the gastric acid profile. Influence of food components and timing of meals.

AlPO4 is generally perceived as a particularly weak antacid. Its neutralizing capacity, when evaluated with the classical Fordtran test at the pH 3 standard, is several times smaller than that of Al(OH)3, which is considered a particularly potent antacid. This difference of in vitro reactivity of the two antacids is largely due to the fact that the pKa value is considerably lower for AlPO4 than for Al(OH)3. The object of this study was to evaluate in vivo and in vitro the impact of the pKa value of these antacids on their efficacy at low pH values and the modulation of their neutralizing capacity through proteins. Since both preparations display a much closer antacid activity at pH 2, we felt it appropriate to reevaluate the comparative in vivo neutralizing capacity of the two antacids at doses matched with their in vitro reactivity at pH 2. In vivo antacid effects were measured by ambulant pH-metry in 18 healthy volunteers after randomized ingestion of carbohydrate or protein meals. Antacid or placebo medication was given 1 and 3 h after meals. At pH 3.0, the standard milieu of the Fordtran test, preparation A, composed of Al(OH)3 and a small fraction of Mg(OH)2, displayed in vitro a neutralizing capacity of 4.4 mmol/ml, whereas this was 0.18 mmol/ml for preparation B, composed solely of AlPO4 (p less than 0.001). When tested at pH 1, 1.5, and 2, however, the ratio between A and B was below 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Improvement of the reproductive performance of sows by treatment with a GnRH superactive analogue.

The effect of a Hungarian-made superactive analogue of GnRH (Ovurelin, D-Phe6-GnRH-EA, Reanal, Hungary) on the postpartal sexual function of sows was monitored. GnRH treatment was carried out on day 19 before weaning. The sows were inseminated at the first oestrus after weaning. GnRH treatment markedly increased litter size at weaning, substantially reduced (to 25 and 50%, respectively) the number of sows failing to come into oestrus after weaning, and increased the number of sows coming into oestrus within one week after weaning by 42.5% and 9%, respectively. These beneficial effects were particularly apparent on the far using closed management technology.

Animals

[Doppler echocardiography in the examination of normally functioning artificial mitral and aortic valves].

Patients with prosthetic valves were investigated by Doppler echocardiography in 902 cases between November 1987 and February 1990. The parameters of 209 of 344 mitral and 258 of 299 aortic prosthetic valves were evaluated. No significant correlation was found between the type of aortic or mitral prosthetic valves and the measured gradient. As concerns the size of the valve and the measured gradient, a close correlation for aortic valve replacement was detected. For a normally functioning mitral prosthetic valve, a maximum early diastolic velocity of less than 2 m/s (16 mm Hg gradient) and a pressure half-time of less than 130 ms (mitral valve area 1.8 cm2) were characteristic. In cases of aortic valve replacements, the maximum velocity was less than 3 m/s (36 mm Hg gradient), except for the small-diameter valves. More than 95% of the cases met these criteria. (Even if small-diameter valves were included, a maximum velocity of more than 3 m/s occurred only in 8.9%.) Doppler echocardiography is a suitable tool for detecting normal prosthetic valve function, while colour Doppler allows the optimal alignment of jet direction and Doppler beam.

Aortic Valve Insufficiency

Decreased inhibition of immune precipitation by sera with the C2 B allotype.

Complement-mediated precipitation inhibiting (CMPI) activity of sera of 5 individuals homozygous for C2 B was compared to that of sera of 20 individuals carrying the common C2 C allotype. Sera with the rare C2 B allotype had a depressed CMPI capacity in both the early (5 min) and the late (60 min) stages of the reaction. We have also compared the CMPI activity of seven homozygous C4A deficient (C4A*Q0) and eight C4B deficient (C4B*Q0) serum samples and did not find significant differences from the controls (no C4 null alleles) in any stage of the reaction. These results indicate that C2 is the critical component in the CMPI reaction of the two constituents of the classical pathway C3 convertase and that C2 B is less active than C2 C.

Antigen-Antibody Reactions

Different motor actions of dynorphins and nonpeptide kappa opioid receptor agonists in the isolated rat colon.

Dynorphin 1-17 has been suggested to be the endogenous ligand for kappa opioid receptors. In this study motor effects of dynorphin 1-17, its N-terminal fragments d-Pen2,d-Pen5-enkephalin (DPDPE) and d-Ser2-[Leu5]enkephalin-Thr (DSLET) without or with pretreatment with naloxone, (-)-2-(furylmethyl)-noretacocine (Mr 2266) or tetrodotoxin (TTX) on the isolated rat colon were compared with those of nonpeptide kappa opioid receptor agonists. Intraluminal pressure changes were measured by perfusion manometry in preparations maintained in a standard organ bath. Dynorphin 1-17, 1-9, 1-8, 1-6, [Leu5]enkephalin, DPDPE and DSLET dose dependently stimulated the tone in the proximal, middle and distal colon with the maximum response at 10(-6) to 10(-5) M. The stimulation produced by Tyr-Gly-Gly-Phe and Tyr-Gly-Gly was 60 and 600 times less potent, respectively. Concentrations of 10(-10) to 10(-6) M des-Tyr1-[Leu5]enkephalin, dynorphin 3-13, 6-17, 1-methyl-2-(3-thienylcarbonyl)-amino-ethyl-5-(2-fluorophenyl)-H-2,3 dihydro-1,4-benzodiazepine, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl) cyclohexyl)-benzene- acetamide-methane sulfonate and (5a,7a,8B)-(-)-N-methyl-(7-(1-pyrrolidinyl)-1-oxaspiro(4,5)-dec-8- yl) benzeneacet-amide produced no changes in motor activity of the rat colon. Only doses exceeding 10(-6) M of the latter three substances stimulated colonic tone. This action was inhibited neither by naloxone nor by Mr 2266. In contrast, the stimulation by dynorphin 1-17 and 1-6 was inhibited to a greater extent by naloxone than by Mr 2266.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Loss of acid suppression during dosing with H2-receptor antagonists.

The suppression of intragastric acidity with H2-receptor antagonists may diminish with repeated administration. To assess the degree and dose-dependence of this tolerance after short-term dosing, two doses of the H2-receptor antagonists, ranitidine (300 mg nocte or q.d.s.) and sufotidine (300 mg or 600 mg b.d.), were given to healthy volunteers for 1 and 2 weeks, respectively. After 1 and 7 days of dosing with ranitidine 300 mg q.d.s. the median 24-h and night-time pH, measured by continuous 24-h pH-metry, dropped from 3.7 to 2.2 and 5.8 to 3.2, respectively (P less than 0.0001 for both). The decline in median pH with ranitidine 300 mg nocte was only significant during the night (from 4.1 to 2.9) (P less than 0.04). There was little change in plasma gastrin concentrations between days 1 and 7 with either dosage. With sufotidine 300 mg b.d. and 600 mg b.d. for 1 and 14 days, the median 24-h pH fell from 3.7 to 2.1 and from 4.6 to 2.6, respectively (P less than 0.0001). The equivalent medians for the night decreased from 6.3 to 2.3 and from 6.6 to 3.1 (P less than 0.0001). Gastrin concentrations did not change after 14 days of dosing with sufotidine 300 mg b.d., but increased significantly during dosing with sufotidine 600 mg b.d. (P less than 0.001). Significant tolerance developed in 7-14 days and it seemed to show some dose relationship. The mechanisms behind tolerance and the role of gastrin are discussed, but remain unclear.

Adolescent

Effects of prolonged administration of metiamide on serum gastrin, gastrin content of the antrum and gastric corpus, and G-cell population in the rat.

The effect of prolonged metiamide administration on serum gastrin, gastrin content of the antrum and gastric corpus, and G-cell population was studied in the rat. A single subcutaneous injection of metiamide (200 mg/kg) at the onset of 16 days of continous treatment with three daily injections was followed by a fivefold increase in serum gastrin level at 4 hr in fasted and at 4 and 6 hr in fed rats. After 16 days of metiamide, the fed rats showed a peak in serum gastrin level of the same magnitude as on day 1, but only at 4 hr. Two hours later, the levels decreased rapidly to basal values. In the fasted animals, the response to metiamide was reduced to a threefold increase at 2 hr. There was no difference in gastrin content of the antrum and gastric corpus nor in volume density of the G-cells after the prolonged treatment compared with the controls. It is concluded that in spite of rises in serum gastrin, prolonged metiamide medication has no effect on the gastrin content of the antrum and gastric corpus nor on the G-cell population in the rat. Furthermore, after prolonged treatment, metiamide-induced gastrin release is diminished.

Animals

Ion content of synaptic vesicles.

Proton induced X-ray emission analysis measurements were performed to determine the P, S, K, Ca Fe, Ni, Cu and Zn ion content of presynaptic vesicles prepared from guinea-pig brain cortex. The number of different ions per single vesicle is calculated using the results of the additional protein content determinations. The ion contents of cholinergic and adrenergic vesicles are compared.

Acetylcholine

Metabolism of C-terminal pentapeptide of gastrin in the rat. Part III. The catabolism of the BOC-pentapeptide and its distribution in the organs.

The metabolism of labelled BOC-14 C-glycine-pentapetide was investigated in rats, both in blood and urine. We report on the following findings: --radioactivity could be measured in the blood even after the disappearance of the bioactive- and immunoreactive pentapeptide. --the bulk of the radioactivity in the blood after 8 minutes originates from a metabolite which, after subsequent systematic chemical identification, proved to be the BOC-14C-glycine fragment of the pentapeptide. --the radioactivity in the urine comes entirely from this split product of the labelled pentapeptide --the organ distribution of radioactivity of labelled pentapeptide was checked after i.v. administration; 1 minute after the injection, most of the radioactivity was found in the liver, followed by the kidney, pancreas, jejunum and lung. After 1 hour, radioactivity could be detected only in the kidneys. It was concluded that the N-terminal amino-acid of the naturally occurring pentagastrin (glycine) remains linked to the BOC protecting group in the course of the catabolism of the molecule and this fragment is excreted in the urine.

Animals

Effect of chloroquine on DNA synthesis in the skin of DLE patients.

Changes in the semiconservative and excision repair DNA synthesis were studied autoradiographically in the skin of 12 patients with discoid lupus erythematosus during Chloroquine treatment (500 mg/day for 8 weeks). The originally increased rate of the semiconservative DNA synthesis in the area of the skin lesions returned to the normal level simultaneous with clinical improvement. No effect on the excision reapir DNA synthesis could be detected.

Adult

Repair of DNA damage in light sensitive human skin diseases.

Repair of UV-light induced DNA damage and changes in the semiconservative DNA synthesis were studied by in vitro autoradiography in the skin of patients with lightdermatoses (polymorphous light eruption, porphyria cutanea tarda, erythropoietic protoporphyria) and xeroderma pigmentosum as well as in that of healthy controls. In polymorphous light eruption the semiconservative DNA replication rate was more intensive in the area of the skin lesions and in the repeated phototest site, the excision repair synthesis appeared to be unaltered. In cutaneous porphyrias a decreased rate of the repair incorporation could be detected. Xeroderma pigmentosum was characterized by a strongly reduced repair synthesis.

Adult