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Biomedical subjects

M Kovács

Publications and source records attributed to M Kovács.

At least 19 recordsLinked to original sources

Mydriatic and antinociceptive effects of intrathecal dexmedetomidine in conscious rats.

A comparison was made of the dose-effect relationship of intrathecally applied dexmedetomidine as concerns its mydriatic and antinociceptive effects in rats. Pupil diameter was measured with a photographic method without anesthesia. Antinociception was measured by means of the tail-withdrawal test. The intrathecal (i.t.) administration of dexmedetomidine led to dose-dependent antinociception (P < 0.05) and mydriasis (P < 0.001). Both effects reached their maximum 10 min after drug application. The tail-withdrawal latency was prolonged by 9 micrograms dexmedetomidine. Mydriasis appeared on administration of a 1 microgram dose and its degree was proportional to the dexmedetomidine dosage up to 12 micrograms. A significant correlation was not found between pupil diameter and tail-withdrawal latency in the same rat after any dexmedetomidine dose. Based on the present experiments, we conclude that the mydriatic effect of i.t. dexmedetomidine appears at a lower dose than its antinociceptive effect. Our results suggest that the assessment of pupillary response is a sensitive method for estimation of the supraspinal effect of i.t. administered alpha 2-adrenoceptor agonists.

Adrenergic alpha-Agonists

An ultrasonographic method for the evaluation of dexmedetomidine on micturition in intact rats.

We describe a simple, noninvasive, nontraumatic, and reproducible ultrasonographic method to determine the effect of the alpha 2-adrenoceptor agonist dexmedetomidine in anesthetic dose (300 micrograms/kg subcutaneously) on the micturition reflex in intact rats. The bladder volumes were estimated by an ellipsoid equation. To validate the reliability of the method, an in vitro model assessment also was performed. The mean difference between estimated and instilled volumes were 27.3 microL (-21.61, 76.23). The highly significant correlation (r = 0.98, p < .001) indicates that the ultrasonography with the equation is a reliable tool. After the dexmedetomidine administration to intact rats, urine dribbling occurred at 30 +/- 4.8 min. The volume threshold for urination was 2100 +/- 100 microL. Although dribbling of the urine was observed almost continuously, significant differences were not observed between bladder volumes obtained at any time (from 10 to 100 min). This study indicates that the alpha 2-adrenoceptor agonist dexmedetomidine inhibits the micturition reflex in intact rats. The method described, which is both noninvasive and nonpainful, may therefore be widely used to quantify in small animals pharmacological effects on the urinary bladder.

Animals

Diverse effects of a potent LH-RH antagonist on the LH and FSH release.

A potent LH-RH antagonist (Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10 LH-RH (Antag) was used to study the differential regulation of FSH and LH secretion by endogenous LH-RH in ovariectomized (OVX) and regularly cycling rats. The endogenous LH-RH was suppressed by single injections of Antag in OVX animals and by long-term treatment with Antag in normal and OVX rats. Serum and pituitary LH and FSH, as well as serum estradiol (E2) and progesterone (P) was determined by RIA during and/or after the treatment. The direct effect of the antagonistic analog on the ovarian P release was tested in vitro using the isolated luteal cell system. Single injections of the Antag in OVX animals caused prompt and marked suppression of the serum LH (-80%), while no decrease of the serum FSH. Long-term treatment with the same analog decreased the serum LH by 50% but did not modify the serum FSH. In normal rats, serum LH dropped to undetectable levels, while serum FSH did not change significantly. Long-term treatment with the antagonist also resulted in divergent alterations in the pituitary gonadotropin concentrations. In OVX animals, the pituitary LH content moderately elevated (+21%), however, the FSH did not change. In normal rats, ovarian cycles were interrupted, and no ovulation appeared during the treatment. The pituitary LH concentration increased by 46%, while the FSH decreased by 43%. Marked depression was found in the serum P (-60%) but no significant change in the serum E2 levels. Incubation of isolated luteal cells with the Antag did not influence the HCG-induced P secretion in vitro, demonstrating that the in vivo inhibitory effect of the antagonistic LH-RH analog on the P secretion asserts not directly on the ovarian LH-RH receptors, but through inhibition of the endogenous LH-RH. Our studies give evidence that the long-term treatment with LH-RH antagonist suppress the LH and P but not the FSH and E2 secretion, and provide new data suggesting the presence of a FSH-releasing factor in the CNS.

Amino Acid Sequence

[Experience with surgical treatment of osteosarcoma].

The authors treated 79 patients with osteosarcoma by surgery and chemotherapy 1975 through 1991. The appearance, localization and differential diagnosis are discussed. Attention is called to the doctor's delay. The effective pre- and postoperative chemotherapy decreased the incidence of the lung metastases and increased the survival rate (71% 3 years overall survival and 41% 5 years survival) and made the limb-sparing surgery possible. The development of the reconstructive surgical technique and new designs of tumor endoprostheses enabled us to perform limb-sparing surgery in more than one third of the cases at the same survival chance. The limb-sparing means a decisive change in the quality of the rehabilitation of the osteosarcoma patients.

Adolescent

[Clinical and histological findings in HCV-caused hepatitis].

58 cases of acute HCV-hepatitis were studied from the debut of acute illness and were followed up over 1-12 years. A mean three week's delay of anti-HCV IgG (Ortho) positivity was observed after the first manifestation of hepatitis. 70.6% relapsed and a chronic hepatitis developed in 37.9%. Seven patients died in HCV-hepatitis. Clinical, chemical, morphological features of HCV-hepatitis different from other viral hepatitis are demonstrated. Persistence of morphological signs of lobular hepatitis after even several months of subacute and chronic outcome has been found characteristic in HCV-hepatitis. Difficulties in interpretation of liver morphology are discussed. Simultaneous evaluation of clinical picture, laboratory markers and morphology is necessary to select cases for therapeutic trials.

Acute Disease

[Delta virus infection in hemodialyzed kidney patients and patients with chronic liver diseases].

Sera of patients with chronic hepatitis and chronic haemodialysed uraemia were tested for both Hepatitis B virus and Hepatitis Delta virus markers from 1985. Hepatitis Delta virus seroconversion was found in 10 of 88 haemodialysed patients and anti-Delta-IgG sero-positivity in 11 of 108 chronic hepatitis patients. The clinical course of Delta superinfections in haemodialysed patients was as follows: 3 infections were symptomless, 7 patients had acute hepatitis, two of the latter group died because of fulminant hepatitis. Of the 11 HBsAg and anti-Delta-IgG positive chronic hepatitis patients 3 had primary hepatocellular cancer.

Carcinoma, Hepatocellular

[Hypereosinophilia syndrome of unknown origin].

The authors describe the case of a 19-year-old man with hypereosinophilic syndrome. At first the clinical picture suggested a localized eosinophilic gastrointestinal disease which rapidly progressed to the fatal disseminated form. The spectrum of hypereosinophilic syndrome is discussed and current thoughts on diagnosis, pathology and treatment presented.

Adult

[Genetic study of diaphragmatic defects].

The occurrence of specific and nonspecific congenital anomalies was determined in first degree relatives of index patients with congenital diaphragmatic defects who were born in Hungary between 1970 and 1979 and were ascertained through a population-based registry. The cases were grouped into Bochdalek types (N = 156), other types (N = 26), unclassified types (N = 55), and multiple congenital anomalies (MCA) cases including those with congenital diaphragmatic defects (N = 96). The sib occurrence in the Bochdalek type was 0.9% (taking into consideration also the unclassified cases or the total material, it was 0.5% or 0.4%, respectively). Specific familial clusters were not found in other types. Neural tube defects were detected in 1.8% of sibs in the total material and 2.4% in MCA cases.

Abnormalities, Multiple

[Hemorrhage in the abdominal cavity caused by ruptured varices].

The authors report on the successful treatment of an unusual varix rupture causing intraabdominal hemorrhage in a patient who suffered from alcoholic hepatic cirrhosis. Simultaneously with the hypogastric pain, hypotension, growing circumference of the abdomen and increasing anaemia--without hematemesis or melena--referred to intraabdominal hemorrhage, which was confirmed by diagnostic paracentesis. Urgent exploratory laparotomy revealed the source of the bleeding and made the adequate surgical treatment possible. The authors are of the opinion that in case of a suspected intraabdominal hemorrhage the exploratory puncture is of diagnostic value and an operation performed without delay may ensure the improvement of the prognosis of this severe complication.

Abdomen

Nonfatal myocardial infarction of women.

Five-hundred women admitted for rehabilitation to the State Hospital for Cardiology 1 to 10 months after myocardial infarction were divided into two groups, viz. group I containing patients less than 40 years of age and group II, in which the patients were older than 41 years. Forty-nine per cent of the patients were blue-collar, whereas 22% of them were white-collar workers; 16.5% had a high qualification, 28% were housewives or retired. The leading symptom at admittance, that is in the post-infarction period, was angina pectoris (32% in group I and 73% in group II). Heart failure, rhythm disturbance and hypertension occurred less frequently. The groups considerably differed from each other in the frequency of risk factors. In group I, smoking (81%), use of anticoncipients (41%) and hyperlipoproteinaemia (32%), while in group II hypertension (49%), smoking (45%), obesity (43%) and hyperlipoproteinaemia (41%) were the main risk factors.

Adult

A nationwide evaluation of multiple congenital abnormalities in Hungary.

A population-based study of 7,049 index patients with multiple congenital abnormalities (MCA) born in Hungary during 1973-1982 was organized by the Hungarian Center for Congenital Anomaly Control. All clinically recognized syndromes and associations which were submitted (2,049) were accepted without any further follow-up. New or supplementary information was requested in the case of unspecified MCA (320). A copy of detailed necropsy records was requested from pathologists in lethal cases (2,022). Following these steps, apparent but not true instances of MCA were excluded (399), and an attempt was made to assign as many of the remainder as possible in 17 well-delineated MCA entities (900). The living index patients with severe MCA were referred where possible to the regional centers for evaluation (864). One hundred and seventy entities were identified, and seven cases were excluded as not representing MCA. In the so-called 3,393 unidentified cases for which no diagnosis was possible, the component abnormalities were tabulated according to their number. The final count was 6,643 cases with MCA, which is equivalent to a birth prevalence of 4.0 per 1,000 total births, and to 10% of recorded cases with congenital anomalies. As a result of this program the proportion of recognized syndromes and associations among children with MCA increased from 29% to 47%. The accuracy of diagnoses has improved, e.g., the occurrence of unspecified cases decreased from 4.5% to 2%. As a result of this study, the number of chromosomal (1,700), Mendelian (557), and teratogenic (104) syndromes and associations (758) was considerably greater than the initial notifications indicated.

Abnormalities, Drug-Induced

Potent GnRH agonists containing L-amino acid derivatives in the six position.

New agonists related to gonadotropin-releasing hormone (GnRH) have been synthesized that are comparable in potency to the GnRH and its superagonists for release of LH and estrus suppression without substitutions with D- or unnatural amino acids in position 6. We now report a series of L-beta-aspartyl-6 GnRH analogs containing only naturally occurring L-amino acids in the whole sequence, exhibiting considerable in vivo biological activity. Dose and time dependent LH release capability of the different analogs in adult male mice, estrus suppression comparisons and blockade of ovulation in female rats are given. The incorporation of L-Asp-OMe and L-Asp-OBzl in position 6 of GnRH resulted in the most potent GnRH agonists (to 12-20xGnRH potency) in this series inducing a biphasic biological response similar to the D-amino acid-6 substituted superactive GnRH analogs. A correlation between the LH releasing potencies of the analogs and their HPLC retention times was also investigated. Peptide synthesis were achieved using either solid phase or solution phase methodology.

Animals