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Biomedical subjects

J Marton

Publications and source records attributed to J Marton.

At least 19 recordsLinked to original sources

New nepenthone and thevinone derivatives.

The diastereoselective reaction of thevinone (2a) and nepenthone (2c) and their dihydro derivatives (2b and d) with Grignard reagents afforded new N-substituted (20S)- and (20R)-phenyl-6,14-ethenomorphinan derivatives (6a-y). The Grignard reaction of the N-substituted-N-demethyl derivatives 4a-f and 4m-r with methylmagnesium iodide resulted in the (20R)-phenyl tertiary alcohols 5a-f and 5m-r, respectively, but the conversion of 4g-1 and that of the N-substituted-dihydrothevinone derivatives with phenylmagnesium bromide afforded the (20S)-phenyl derivatives 5g-l and 5s-y, respectively. The N-cyclopropylmethyl-, N-beta-phenylethyl-, and N-propyl derivatives were prepared by the 3-O-demethylation of compounds 5. For the synthesis of the N-allyl-, N-dimethylallyl-, and N-propargyl compounds 2a-d were reacted with the corresponding Grignard reagent, and treatment of the products with cyanogen bromide gave the cyanamides 8a-d. These latter compounds were transformed into 10a, b,d, whose alkylation led to the target derivatives 6d-f, j-l, p-r, and w-y. The biochemical investigation of these substances showed that the affinities to the delta-opioid receptors were high, but the selectivity was low. In two cases (6c and 11d) a mu-opioid receptor specificity was observed.

Animals

[While science grows and the number of libraries decreases, what will happen to information? (Decrease of medical journals in Hungary)].

The differences between the 1982 and 1994 subscriptions of the leading medical journals were investigated. Sample journals were taken from the impact factor rank lists of the Science Citation Index. The 1994 level was 45% lower than that of 1982. The information supply of the medical universities has weakened too, especially because they have too many small institutional library units. They are not able to supply the literature necessary to their readers and to the Hungarian medical audience.

Forecasting

Bile leakage following laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) is now the treatment of choice for gallstones, but there has been concern that bile leakage with LC is more frequent than after open cholecystectomy (OC). We have analyzed our experience of this complication with regard to both its incidence and management. From a consecutive series of 500 LC, in which both operative cholangiography and drainage of the gallbladder bed were routine, bile leakage was identified in ten patients (2%). There was no bile duct injury. Nine of the ten patients presented with bile in the drain within 24 h of operation and one patient presented 1 week after operation with a subphrenic collection. Of the ten patients, five settled spontaneously. Of the five remaining patients, two needed laparotomy--one for a subphrenic collection not responding to percutaneous drainage and one for biliary peritonitis. One patient was treated by relaparoscopy and suture of a duct of Luschka and one patient had successful percutaneous drainage of an infected collection; the fifth patient who presented with a late subphrenic collection of bile was shown at endoscopic retrograde cholangiopancreatography (ERCP) to have a cystic duct stump leak and was treated with an endoscopic stent. Bile leakage is seen more frequently after LC than OC for reasons that are currently unclear. We believe that the use of routine gallbladder bed drainage is justified for this reason alone. The majority of bile leaks settle either spontaneously or with minimally invasive intervention.

Adult

Fundus-first laparoscopic cholecystectomy.

Removal of the gallbladder with commencement of dissection at the fundus is well recognized as a safe technique during difficult "open" cholecystectomy because it minimizes the risks of damage to the structures in or around Calot's triangle. We report here the routine employment of liver retractors and fundus-first dissection during laparoscopic cholecystectomy (LC) as an alternative to techniques previously described. Retraction of the liver and "fundus-first" dissection was used in 53 patients who underwent laparoscopic cholecytectomy. There were 16 male and 37 female patients. Seven were operations performed during an acute admission and 20 had moderate or severe adhesions involving the gallbladder. Thirteen patients had a preexisting abdominal incision. The procedure was successful in 52 patients (98%), but in one patient it was converted to open operation because of dense adhesions. Median duration of operation was 90 min (range 35-240 min). There was no mortality and two complications (persistent right upper quadrant pain for 2 weeks after operation and bile leakage from the gallbladder bed). The facility to retract the liver and carry out a fundus-first dissection extends techniques developed for "open" surgery into the laparoscopic arena. It offers the surgeon the safety and versatility during laparoscopic cholecystectomy that it confers during conventional open surgery.

Acute Disease

[Results of extended resection of tumors of the colon and rectum].

The postoperative lethality and 5 year survival of elective extended colon resections in 59 locally advanced colorectal tumour cases has been evaluated. The operation has been extended for one adjacent organ in 47 (Groups I.) and for two or more organs in 12 cases (Groups. II.). The postoperative lethality was 47/1 and 12/2 respectively (P less than 0.01). However the 5 year survival proved to be similar--42% and 40% respectively in both patients group. The 5 year survival of patients group I. and II. was not significantly different comparing to the "simple" elective colorectal resections on the patients in Dukes C stadium operated on in the same period of time. Significantly better 5 year survival has been observed in the patients groups. I. and II. comparing to the outcome of the elective palliative (anus prae and ileo- or colo-colostomies) colorectal operations. The results certify the value of the radical surgical procedures in the locally advanced tumor cases.

Colectomy

Hypophysial trophic hormone response to adrenalectomy and ether stress in rats bearing anterior pituitary tissue in third ventricle of the brain.

Inhibitory effect of anterior pituitary tissue implanted into the brain on trophic hormone secretion was studied under resting conditions and after adrenalectomy or ether stress. The weight of pituitary gland in rats bearing anterior pituitary graft in the third ventricle was decreased and the body weight gain was retarded. The levels of ACTH, PRL and GH, but not those of FSH and LH in plasma were significantly lower as compared with all control groups. There was a pituitary ACTH, PRL and GH response to adrenalectomy and ether stress in these rats. Besides supporting literary data on the inhibitory effect of additional pituitary grafts on the adenohypophysis, these findings indicate that pituitary implants did not cause any appreciable alteration of pituitary responsiveness, at least to adrenalectomy or ether stress.

Adrenal Glands

Studies on the vasoocclusive crisis of sickle cell disease. III. In vitro and in vivo effect of the pyrimido-pyrimidine derivative, RA-233: studies on its mechanism of action.

Red cell deformability was found to be impaired in SS- and SC-genotype and to a lesser extent SA-genotype red blood cells as compared with those of AA-genotype. RA-233 in vitro improved deformability according to a bell-shaped dose-response curve. RA-233 also prevented experimental vasoocclusive crisis in Macaca arctoides. Deoxygenation of SS-genotype red cells resulted in sickle shape transformation, ATP depletion, potassium efflux, and attachment of hemoglobin molecules to the membrane. These changes were prevented by RA-233. Suspending SS-genotype red blood cells in potassium rich tris-buffer also prevented potassium efflux during deoxygenation and also decreased cellular deformability. RA-233 had no effect on osmotic fragility of SS-genotype red blood cells.

Adult

Further data on the origin of gonadotropin releasing hormone in the median eminence of the rat hypothalamus.

Gonadotropin releasing hormone (GnRH) content of the two halves of the median eminence of the rat hypothalamus was determined by radioimmunoassay three weeks after three different unilateral knife cuts around the preoptic area. A unilateral cut in front or above the area caused a more than 25% decrease in the GnRH content of the two halves of the median eminence. A cut lateral to the preoptic region had only a slight effect similar to that observed after sham operations. The data suggest that probably more than 50% of the rat median eminence GnRH derives from outside the preoptic-suprachiasmatic region. The GnRH fibres projecting to the median eminence but arising from outside the preoptic region, probably mainly from GnRH perikarya in the limbs of the diagonal band of Broca and septum, enter this area partly from rostral and partly from above, but not from lateral direction. partly from rostral and partly from above, but not from lateral direction. Several of these fibres probably cross before terminating in the median eminence.

Animals

Increased life expectancy resulting from addition of L-deprenyl to Madopar treatment in Parkinson's disease: a longterm study.

In an open, uncontrolled study the longterm (9 years) effect of treatment with Madopar alone (n = 377) or in combination with l-deprenyl (selegiline, selective monoamine oxidase type B inhibitor) (n = 564) have been compared in Parkinsonian patients. In patients who lost their response to conventional Madopar therapy the addition of l-deprenyl resulted in a significant recouping of levodopa effect. The survival analysis revealed a significant increase of life expectancy in Madopar--l-deprenyl group regardless of the fact whether or not the significant demographic differences between the two groups were taken into account. Although the mechanism underlying this action of l-deprenyl is not known, the results are interpreted as indicating l-deprenyl's ability to prevent or retard the degeneration of striatal dopaminergic neurons. l-Deprenyl is the first anti-Parkinson drug having such a property. This hypothesis is not far fetched since l-deprenyl selectively prevents the degeneration of striatal dopaminergic neurons induced in animals by the illicit drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since latter compound is known to cause Parkinsonism in man and primates or Parkinson-like neurochemical and pathological changes in other animals the implications of the present study involving monoamine oxidase activity and l-deprenyl are apparent.

Adult

Inducibility of the hepatic microsomal monooxygenase system experimentally reduced to a minimum amount/activity. Effect of hypophysectomy, partial hepatectomy and phenobarbital/toluene treatment on the hepatic polysubstrate monooxygenase system in rats.

Sham-operated, hypophysectomized, partially hepatectomized and hypophysectomized + partially hepatectomized groups of CFY rats were treated with phenobarbital (40 mg/kg/day) per os or physiological saline once a day, or toluene-vapour (inhalation: 4,000 mg/m3, 8 h/day), for 3 days. The polysubstrate monooxygenase (PSMO) system of the liver was induced by phenobarbital after all kinds of surgical interventions. Inducibility of the enzyme system was the highest in the group with combined hypophysectomy + partial hepatectomy and decreased in order in the groups with partial hepatectomy, hypophysectomy and sham-operation. The relative cytochrome P-450 content (quantity of cytochrome P-450/100 g b.w.) was the lowest after combined operation, higher in partially hepatectomized and hypophysectomized animals and it was the highest in the sham-operated group. Hypophysectomy after partial hepatectomy seems to inhibit hepatic regeneration and to increase the inducibility of the enzyme by phenobarbital, at the same time. Phenobarbital treatment brought about SER proliferation in a part of liver cells, in each group. In case of repeated liver damage due to the consequences of hypophysectomy, partial hepatectomy, phenobarbital administration, a group of the liver cells responds to the first, another to the second, but even after the third injury a group of the liver cells maintained its regular structure. The hypothetical hepatotoxic effect of toluene, a widely used industrial solvent, has been tested. Hepatotoxicity has been excluded. The minimum non-specific hepatotoxic effect of the solvent was not augmented by either partial hepatectomy or hypophysectomy, or by the combination of the two. In all the experimental groups toluene increased the hepatic cytochrome P-450 level and induced a moderate increase in SER. Inducibility of the enzyme system after toluene inhalation was similar to that of the enzyme system after phenobarbital treatment in each group.

Animals

[Analysis of perinatal morbidity and mortality in cases of dysmaturity].

The authors have examined the case-histories of the intrauterine retarded neonates on the basis of their obstetrical material during a four years period. They did not find such pregnancy complications in more of the half of their cases, which should have drown the attention to the possibility of the intrauterine retardation. The perinatal mortality of the dysmature babies was significant higher than the global perinatal mortality of their ward. They emphasize the importance of the early diagnosis. They suggest to spread the screening examinations. We can prevent the intrauterine death with the help of the hospitalization of the screened pregnants and with the instrumental and endocrine monitorisation of the pregnancy.

Birth Weight

On the origin of luteinizing hormone releasing hormone and somatostatin in the median eminence of the rat hypothalamus.

Luteinizing hormone releasing hormone (LHRH) and somatostatin content of the two halves of the median eminence of the rat hypothalamus were determined by radioimmunoassay three weeks after following deafferentations: (1) unilateral knife cut in front of, laterally and above the preoptic area (preoptic deafferentation); (2) unilateral arched cut at the midlevel of the suprachiasmatic region (suprachiasmatic deafferentation); (3) unilateral arched cut behind the optic chiasm (retrochiasmatic deafferentation); (4) cutting around the medial basal hypothalamus on one side starting with the cut at the posterior level of the optic chiasm (complete deafferentation). Preoptic deafferentation caused a more than 50% decrease in the LHRH content of the ipsilateral half of the median eminence. The reduction in LHRH was even greater (about 70%) in rats with suprachiasmatic deafferentation and only about 15% of the neurohormone was found in the ipsilateral half of the median eminence after unilateral retrochiasmatic or complete deafferentation. The median eminence somatostatin showed practically no change after unilateral preoptic deafferentation, while it was reduced by about 50, 60 and 80% in the ipsilateral half median eminence after a unilateral suprachiasmatic, retrochiasmatic and complete deafferentation, respectively. The results are consistent with the assumption that the majority of the LHRH perikarya projecting to the median eminence are located partly in the preoptic-anterior hypothalamic area and partly in brain regions in front of or above this area. Most of the somatostatin perikarya with terminals in the median eminence are in the preoptic-anterior hypothalamic region.

Afferent Pathways

(D-Met2,Pro5)-enkephalinamide-induced blockade of ovulation and its reversal by naloxone in the rat.

The effects of (D-Met2,Pro5)-enkephalinamide--a superactive enkephalin analogue--on the preovulatory discharge of gonadotrophic hormones and on ovulation were investigated. Injection of the opioid (16 nmol) into a lateral cerebral ventricle of regularly cycling female rats immediately before the critical period on the day of proestrus resulted in a blockade of ovulation and in a concomitant depression of the preovulatory plasma luteinizing hormone and follicle-stimulating hormone levels. A smaller dose of the opioid (2 nmol) did not inhibit ovulation. The inhibition of the preovulatory gonadotrophic hormone discharge and the blockade of ovulation by the opioid were reversed by naloxone administration. Our data are consistent with the view that the endogenous opioid peptides may be involved in the physiological regulation of the central neural events which lead to ovulation in the rat.

Animals

Evaluation of a radioimmunoassay for plasma adrenocorticotrophin.

A radioimmunoassay for plasma ACTH has been described and evaluated. Rabbit antiserum produced by immunization with [Asp25, Ala26, Gly27,]-alphah-corticotrophin-(1--28)-octacosa-peptide (a sequence analogue of alphah1--28-ACTH) bovine gamma globulin conjugate was used. The antiserum is specific for the NH2-terminal portion of the ACTH molecule and cross-reactivity of human, porcine and rat ACTH in the system has been demonstrated. Reasonable agreement was found between estimates obtained by bioassay and radio-immunoassay of the ACTH content of rat pituitary gland incubation media, indicating a close relationship between the sequence of ACTH recognized by the antibodies and the sequence possessing the steroidogenic activity. Measurement of the amount of ACTH in the plasma required the preliminary extraction and concentration of the hormone. Over a range of concentrations between 3.5 and 3600 pg/ml, extraction recovery was independent of the initial concentration of ACTH in the plasma. Extraction gave rise to no changes in the immunological properties of standard ACTH. The concentration of immunoreactive ACTH in rat plasma was 48 +/- 3.6 (S.E.M.) pg/ml in the morning and 106 +/- 9.9 pg/ml in the afternoon. Exposure to either for 5 min and subsequent laparotomy gave rise to a significant increase in the concentration of immunoreactive ACTH in the plasma. The resting level of ACTH and the ACTH response to stress were both significantly higher 1 and 7 days after adrenalectomy. Intravenous injection of a hypothalamic extract elicited a considerable rise in the concentration of immunoreactive ACTH in the plasma, but no response was seen after oral administration of this partially purified extract. The sensitivity, precision and specificity of this ACTH radioimmunoassay make it a useful tool for studying pituitary--adrenal physiology.

Adrenocorticotropic Hormone

Preparation and assessment of antisera to ACTH.

Antisera to ACTH were produced in rabbits injected repeatedly at multiple intradermal sites with synthetic [Asp25, Ala26, Gly27]alphah-corticotropin-(1-28)-octacosapeptide-bovine gamma globulin conjugate (octacosapeptide is a sequence analogue of alphah1-28-ACTH). Antibodies to extracted human or porcine ACTH were detected in all of the sera 1 month after immunization. A considerable proportion of the antisera obtained from a single final bleeding 5 months after the primary immunization were suitable for sensitive radioimmunoassay. The antisera were shown to neutralize the steroidogenic activity of ACTH in an isolated rat adrenal cell bioassay system. Titres estimated from antiserum dilution curves and relative avidities from the standard curves were compared. It was possible to detect picogram amounts of ACTH in plasma-free medium with the best antisera. The method described is an effective means of producing anti-sera to the weakly immunogenic N-terminal fragment of the ACTH molecule.

Adrenal Glands

Quantitative studies on the supraoptic nucleus in the rat. I. Synaptic organization.

Four types of synapses: axo-axonic, axo-dendritic, axon-spine, and axo-somatic were distinguished in the supraoptic nucleus in the rat. The density of synaptic terminals (boutons) in this nucleus is 35.17-10(6)/mm3 hence there are over 5 million boutons on each side, and on the average 596 per neuron. Only about one third of the axon terminals in this nucleus originate outside the nucleus and its immediate neighbourhood. Two thirds appear to be of intranuclear or otherwise of local origin. This could be explained by assuming either numerous intranuclear axon collaterals or interneurons having richly arborizing axons, or possibly both.

Animals