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Biomedical subjects

L Bartha

Publications and source records attributed to L Bartha.

At least 19 recordsLinked to original sources

Consensus perspectives on surgery in haemophilia patients with inhibitors: summary statement.

Summary. Participants in an international workshop on surgery in haemophilia patients with inhibitors developed a consensus summary of the findings and conclusions of the meeting. In the consensus, participants agreed upon revised definitions for minor and major surgery, including an intermediate degree of surgery. An evaluation system of intraoperative and postoperative bleeding was developed. Recommended doses of FEIBA((R)) and rFVIIa (both in bolus injections and in continuous infusion) for surgery were agreed. Participants also agreed on the main blood tests to be performed peri-operatively. They also suggested the need of a prospective evaluation in the future. Finally, the approximate number of surgical procedures and costs performed on haemophilia patients with inhibitors were analysed.

Adult↗

Number processing in temporal lobe epilepsy.

BACKGROUND: Specific cognitive impairments have been found in association with mesial temporal lobe epilepsy (TLE), such as deficits in declarative memory or verbal abilities. No attention has been paid so far to possible deficits in number processing. OBJECTIVE: To investigate deficits in number processing in patients with TLE. METHODS: Numerical abilities were assessed in 28 right handed patients with medically intractable unilateral TLE and in a control group. RESULTS: No differences between patients and controls were found in analogue number processing with Arabic input, in a comparison task, or in simple addition and simple subtraction; however, there were significant group differences in tasks with verbal input, in simple division, in complex mental calculation, in a semantic knowledge task, and in conceptual tasks. Only minor differences were found between patients with right and left TLE. CONCLUSIONS: While numerical deficits may be expected in patients with left sided TLE, it is open for discussion why patients with right sided TLE also show numerical deficits.

Adult↗

Peri-ictal water drinking lateralizes seizure onset to the nondominant temporal lobe.

The authors describe seven patients with medically refractory temporal lobe epilepsy whose seizures were associated with peri-ictal water drinking behavior. Presurgical evaluation, including video-EEG monitoring, MRI, SPECT, and neuropsychological testing, revealed a seizure onset in the nondominant temporal lobe. All patients had an excellent outcome after epilepsy surgery. Peri-ictal water drinking may represent a lateralizing sign indicating seizure onset in the nondominant temporal lobe.

Adolescent↗

Learning complex arithmetic--an fMRI study.

Aim of the present functional magnet resonance imaging (fMRI) study was to detect modifications of cerebral activation patterns related to learning arithmetic. Thirteen right-handed subjects were extensively trained on a set of 18 complex multiplication problems. In the following fMRI session, trained and untrained problems (closely matched for difficulty) were presented in blocked order alternating with a number matching task and a fact retrieval task. Importantly, left hemispheric activations were dominant in the two contrasts between untrained and trained condition, suggesting that learning processes in arithmetic are predominantly supported by the left hemisphere. Contrasting untrained versus trained condition, the left intraparietal sulcus showed significant activations, as well as the inferior parietal lobule. A further significant activation was found in the left inferior frontal gyrus. This activation may be accounted for by higher working memory demands in the untrained as compared to the trained condition. Contrasting trained versus untrained condition a significant focus of activation was found in the left angular gyrus. Following the triple-code model [Science 284 (1999) 970], the shift of activation within the parietal lobe from the intraparietal sulcus to the left angular gyrus suggests a modification from quantity-based processing to more automatic retrieval. The present study shows that the left angular gyrus is not only involved in arithmetic tasks requiring simple fact retrieval, but may show significant activations as a result of relatively short training of complex calculation.

Adult↗

Effect of endoscopic third ventriculostomy on neuropsychological outcome in late onset idiopathic aqueduct stenosis: a prospective study.

OBJECTIVE: To undertake a prospective study of the long term neuropsychological outcome in patients with late onset idiopathic aqueduct stenosis (LIAS) after endoscopic third ventriculostomy. METHODS: Six patients with LIAS were evaluated pre- and postoperatively using magnetic resonance imaging (MRI) and standardised psychometric testing procedures. Endoscopic third ventriculostomy was done using standard surgical techniques. The mean long term follow up was 81.2 weeks. RESULTS: Preoperatively, all patients had cognitive impairment, four of them showing deficits in several cognitive domains. After endoscopic third ventriculostomy, all patients improved clinically and had ventricular size reduction on MRI. Postoperative neuropsychological testing showed that five patients achieved normal or near normal cognitive functions, and one improved moderately. CONCLUSIONS: Endoscopic third ventriculostomy caused a substantial improvement in the neuropsychological deficit of LIAS patients. This was also true for patients with enlarged ventricles that might be diagnosed radiologically as "arrested hydrocephalus."

Adult↗

Asymmetric termination of secondarily generalized tonic-clonic seizures in temporal lobe epilepsy.

In patients with secondarily generalized tonic-clonic seizures (sGTCS) an asymmetric termination of the clonic phase can be observed. The authors systematically analyzed this phenomenon in patients with temporal lobe epilepsy (TLE). Thirty-nine sGTCS from 29 patients with TLE who underwent successful epilepsy surgery were analyzed, in addition to a prospectively collected group of 28 patients with TLE who had 35 sGTCS. The clonic phase of sGTCS did not end synchronously in 65.7% of all patients and in 59.4% of all seizures. In 79.3% to 80% this was ipsilateral to the hemisphere of seizure onset, and there was excellent interobserver agreement.

Adult↗

Mosaicplasty for the treatment of articular defects of the knee and ankle.

Efficacious treatment of full-thickness cartilage defects of the weightbearing surfaces is a multi-faceted challenge for the orthopaedic surgeon. Autologous osteochondral transplantation represents one solution: to bring about a hyaline or hyalinelike repair of the defected area. The current authors discuss the experimental background and their 8 years of clinical experience with the autologous osteochondral mosaicplasty. Several series of animal studies and subsequent clinical practice have confirmed the survival of the transplanted hyaline cartilage. Hyaline cartilage and fibrocartilage fill the donor sites located on the nonweightbearing surfaces and surfaces that bear less weight. Clinical scores, imaging techniques, control arthroscopies, histologic examination of biopsy samples, and cartilage stiffness measurements were used to evaluate the clinical outcomes and quality of the transplanted cartilage. According to these investigations, femoral condylar implantations have shown good to excellent results in 92%, tibial resurfacing in 88%, patellar and/or trochlear mosaicplasties in 81%, and talar procedures in 94% of patients. The Bandi score showed long-term donor site disturbances in 3% of patients. Fifty-eight of the 68 control arthroscopies had good gliding surfaces, histologically-proven survival of the transplanted hyaline cartilage, and fibrocartilage covering of the donor sites. In the entire series, there were four deep infections and 34 painful hemarthroses after surgery. A multicentric, comparative, prospective evaluation of 413 arthroscopic resurfacing procedures (mosaicplasty, Pridie drilling, abrasion arthroplasty, and microfracture cases in homogenized subgroups) showed that mosaicplasty gave a more favorable clinical outcome in the long-term followup, than the other three techniques. Intermediate-term evaluation of the femoral condylar implantations (3-6-years followup) and talar mosaicplasties (3-7-years followup) confirmed the durability of the early results. From these encouraging results from an increasingly large series and similar results from other centers, it seems that autologous osteochondral mosaicplasty may be a viable alternative treatment of localized full-thickness cartilage damage of the weightbearing surfaces of the knee and other weightbearing synovial joints.

Adolescent↗

Synthesis of peptide and pseudopeptide amides inhibiting the proliferation of small cell and epithelial types of lung carcinoma cells.

Small cell lung cancer (SCLC) cell lines produce and secrete various peptide hormones, e.g. bombesin (BN)/gastrin releasing peptide (GRP) like peptides that are proposed to function as their autocrine growth factors. To inhibit the proliferative effect of these hormones we have synthesized short chain BN[7-14]-analogues replacing the C-terminal peptide bond by a methylene-amino (-CH2NH-) unit and introducing D-Phe or D-Ser into position 12. As several substance P (SP) analogues were found to inhibit the growth of SCLC cells, some short chain SP-analogues have been synthesized. (Pseudo)octapeptides were synthesized in solution, by fragment condensation using the DCC/HOPfp method. Fragments and SP-analogues were synthesized stepwise using pentafluorophenyl esters. The resistance to hydrolysis of the reduced peptide bond made permitted exact quantification of the Leupsi(CH2NH)Leu pseudopeptide in hydrolysates. The binding ability of both types of peptides to BN-receptors on Swiss 3T3 mouse fibroblast cells and their antiproliferative effect on NCI-H69 human SCLC cell line have been tested and compared with a short chain SP-antagonist pHOPA-D-Trp-Phe-D-Trp-Leu-Leu-NH2 (R) previously described as a potent inhibitor of SCLC proliferation. While BN-analogues showed weak activity in inhibition of proliferation of SCLC cells, SP-analogues 6: D-MePhe-D-Trp-Phe-D-Trp-Leu(psi)(CH2NH)-Leu-NH2 and 7: D-MePhe-DTrp-Phe-D-Trp-Leu-MPA, in spite of greatly diminished affinity towards the BN-receptor, inhibited SCLC proliferation more effectively than R (6: IC50 = 2 microM, 7: IC50 = 5 microM and R: IC50 = 10 microM). Moreover, 6 inhibited the respiratory activity of SK-MES 1 epithelial type of lung carcinoma cells in proliferating but not in the quiescent state, suggesting that the antiproliferative effect of these compounds is not due to simple cytotoxicity. These short chain analogues of SP might be promising candidates as therapeutic agents in the treatment of SCLC.

3T3 Cells↗

New short-chain analogs of a substance-P antagonist inhibit proliferation of human small-cell lung-cancer cells in vitro and in vivo.

Human small-cell lung-cancer cells (SCLC) produce and secrete gastrin-releasing peptide (GRP), the mammalian equivalent of bombesin (BN). There is some evidence to suggest that GRP is an autocrine regulator of SCLC cell growth. In the search for potent BN antagonists, several substance-P (SP) analogs were found to inhibit the growth of SCLC cells. We found that a known short-chain SP antagonist, pHOPA-DTrp-Phe-DTrp-Leu-Leu-NH2(NY3238), inhibits the binding of 125I-Tyr4-BN on Swiss 3T3 cell line expressing BN receptors, as well as the proliferation of NCI-H69 SCLC cells. In this study we tested several analogs of NY3238 and we found that NY3521 and NY3460 are more effective in inhibition of proliferation of SCLC cells but less potent in inhibition of binding of 125I-Tyr4-BN on Swiss 3T3 cells than NY3238. Furthermore, we detected specific binding of radiolabelled NY3238 even below 1 nM on NCI-H69 cells that could have been inhibited by SP and NY3460 rather than by BN. In addition to these in vitro studies, NY3460 proved to be effective in inhibiting the growth of NCI-H69 SCLC xenografts in nude mice in vivo. These analogs of NY3238 could be promising therapeutic agents in the treatment of SCLC.

3T3 Cells↗

Effect of dexamethasone implanted in different brain areas on the morphine-induced PRL, GH and ACTH/corticosterone secretion.

We studied the effect of dexamethasone (DEX) implantation in male Wistar rats to elucidate the site of action of morphine-induced prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH) and corticosterone (B) secretion. DEX or cholesterol was implanted in the close vicinity of the paraventricular (PVN), or the arcuate nuclei (ARN) of the hypothalamus or into the hippocampus. Five days after implantation blood samples were taken 30 min after i.p. morphine by decapitation or through an indwelling cannula 15, 30, 60 min after i.v. injection. DEX implanted near the PVN resulted in a blockade of morphine-induced ACTH and B secretion. In contrast, GH response to morphine was enhanced, while that of PRL was unchanged. DEX implanted near the ARN significantly inhibited the PRL-releasing effect of morphine, but was without any influence on the PRL secretion induced by haloperidol. There was a partial reduction in the B response to morphine, and GH secretion was unchanged. Dorsal hippocampal implants were without any effect on the morphine-induced GH, PRL or B secretion. We suggest that the site of glucocorticoid inhibitory action in the hypothalamus is the PVN for the opiate-induced ACTH/B secretion, and the ARN for the morphine-induced PRL release. The enhanced GH response to morphine observed in DEX-PVN implanted rats might be due to a decreased somatostatin tone.

Adrenocorticotropic Hormone↗

Prolactin response to morphine in intact and adrenalectomized lactating rats.

To examine the hypothesis that the increased adrenocortical activity during lactation induced the loss of the prolactin (PRL) -releasing effect of morphine, we studied the effect of morphine in adrenalectomized (ADX) and sham-operated primiparous lactating Wistar rats. Animals were adrenalectomized 4 days after delivery. On day 11 of lactation (7 days after ADX), pups were separated from their mother 2 h before morphine or haloperidol injection. Intravenous injection of 5 mg/kg morphine did not change plasma PRL levels in the sham-operated lactating rats, but it resulted in a significant increase of plasma PRL levels in ADX lactating animals, with or without corticosterone replacement. Catalepsy following 10 mg/kg i.v. morphine was also markedly enhanced in ADX lactating animals. The PRL response to 0.5 mg/kg haloperidol was higher in ADX lactating animals than that in the controls. Morphine given 2 h after haloperidol treatment resulted in a further increase of plasma PRL in ADX, but not in the sham-operated lactating animals. These results suggest that adrenal hyperfunction may lead to a loss of sensitivity to morphine during lactation.

Adrenalectomy↗

Reevaluation of the role of alpha 2-adrenoreceptors in morphine-stimulated release of growth hormone.

The relationship between opioidergic and alpha 2-adrenergic system in the regulation of GH secretion was studied using a novel alpha 2-antagonist, CH-38083, and chronic treatment with yohimbine or clonidine. In male Wistar rats morphine (3 mg/kg s.c.), and clonidine (31 micrograms/kg i.p.) induced a significant increase in plasma GH levels. The pretreatment with the alpha 2-antagonist yohimbine (1 and 3 mg/kg) effectively inhibited the GH releasing effect or morphine and clonidine. CH-38083 at the dose of 1 mg/kg did not interfere with the morphine-induced GH secretion, while it fully antagonized the GH-releasing effect of clonidine. Higher doses (3 and 5 mg/kg) of CH-38083 only partly inhibited GH secretion induced by morphine. In rats chronically treated with clonidine (2 micrograms/ml in the drinking water for 14 days) the GH response to an injection of clonidine was blocked, while the effect of morphine on the GH secretion remained unchanged. In long-term castrated rats the effect of clonidine (15, 31 and 250 micrograms/kg i.p.) on the GH secretion was significantly blunted, while the GH-releasing effect of morphine (1, 3 and 5 mg/kg s.c.) remained unchanged. The replacement of testosterone (10 mg/kg for 4 days) in castrates restored the effect of clonidine, whereas it decreased the stimulatory action of morphine on the GH secretion. In rats chronically treated with yohimbine (2 mg/kg i.p. 2-3 times daily for 14 days until sacrifice), the GH response to a high dose of clonidine (0.5 mg/kg i.p.) was blocked, while the effect of morphine (5 mg/kg s.c.) was significantly enhanced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Inhibition of suckling-induced prolactin release by dexamethasone.

The effect of dexamethasone (DEX) treatment (400 and 200 micrograms/kg BW 21 and 2 h before suckling stimulus, respectively) on suckling- and domperidone (DOMP)-induced PRL release was investigated in freely moving, primiparous lactating rats. DEX completely blocked suckling-induced plasma PRL release without affecting DOMP-induced release of the hormone suggesting a central action of DEX. The effect was transient because it could not be detected on the second day of testing. The effect of DEX implanted in three different brain areas on suckling- and DOMP-induced PRL release was also tested. Implants surrounding the hypothalamic paraventricular nuclei and dorsal hippocampus failed to affect PRL release induced by suckling stimulus. Surprisingly, DEX suppressed PRL release induced by suckling stimulus when it was implanted into the medial basal hypothalamus. These findings demonstrate that DEX is a potent inhibitor of the suckling-induced PRL release. They also indicate that the site of action of DEX is not at the anterior pituitary gland or the paraventricular nuclei and hippocampus because DEX treatment and DEX implants had no effect on plasma PRL levels induced by DOMP and suckling stimulus, respectively. Our data suggest that the effect of DEX is mediated through a region of the medial basal hypothalamus. The observed transient block in suckling-induced PRL release may be physiologically relevant during stress in lactating mothers for conserving pituitary stores of the hormone needed for milk production or being able to adapt to a rapid change in osmoregulation.

Animals↗

The effect of systemically and locally administered steroids on VIP-like immunoreactive cells in the paraventricular nucleus of adrenalectomized rats.

Seven days after adrenalectomy (ADX) the number of vasoactive intestinal peptide (VIP)- and corticotropin-releasing factor (CRF)-immunoreactive cells in the parvocellular part of the rat paraventricular nucleus (PVN) increased markedly. Dexamethasone in the drinking water (started immediately after ADX) or its local implantation around the hypothalamic PVN reduced the ADX-induced increase in the number of VIP- and CRF-like immunoreactive neurones. The present results suggest that PVN might be the site at which glucocorticoids inhibit the increase in VIP-positive cells after ADX.

Adrenal Glands↗