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Biomedical subjects

Z Molnár

Publications and source records attributed to Z Molnár.

At least 37 records · Page 2Linked to original sources

Organization of visual cortex in the northern quoll, Dasyurus hallucatus: evidence for a homologue of the second visual area in marsupials.

Two visual areas, V1 and V2 (first and second visual areas), appear to be present in the posterior neocortex of all eutherian mammals investigated so far. However, previous studies have not established whether an area homologous to V2 also exists in metatherian mammals (marsupials). Using electrophysiological techniques, we mapped the visual receptive fields of neurons in the striate and peristriate cortices of the northern quoll, an Australian marsupial. We found that neurons in a 2-mm-wide strip of cortex rostrolateral to V1 form a single, relatively simple representation of the complete contralateral hemifield. This area resembles V2 of eutherians in several respects: (i) neurons in the medial half of the peristriate area represent the lower visual quadrant, whereas those in the lateral half represent the upper visual quadrant; (ii) the vertical meridian of the visual field is represented adjacent to V1, while the visual field periphery is represented along the lateral and rostrolateral borders of the peristriate area; (iii) there is a marked anisotropy in the representation, with a larger magnification factor parallel to the V1 border than perpendicular to this border; and (iv) receptive fields of multiunit clusters in the peristriate cortex are much larger than those of cells in V1 at comparable eccentricities. The cortex immediately rostral and lateral to V2 did not respond to visual stimulation under our recording conditions. These results suggest that V1 and V2 together form a 'core' of homologous visual areas, likely to exist in all therian mammals.

Animals↗

Characterization of nodular neuronal heterotopia in children.

Neuronal heterotopia are seen in various pathologies and are associated with intractable epilepsy. We examined brain tissue from four children with subcortical or periventricular nodular heterotopia of different aetiologies: one with severe epilepsy following focal brain trauma at 17 weeks gestation, one with hemimegalencephaly and intractable epilepsy, one with focal cortical dysplasia and intractable epilepsy, and one dysmorphic term infant with associated hydrocephalus and polymicrogyria. The connectivity of nodules was investigated using histological and carbocyanine dye (DiI) tracing techniques. DiI crystal placement adjacent to heterotopic nodules revealed numerous DiI-labelled fibres within a 2-3 mm radius of the crystals. Although we observed labelled fibres closely surrounding nodules, the majority did not penetrate them. Placement of DiI crystals within nodules also identified a limited number of projections out of the nodules and in one case there was evidence for connectivity between adjacent nodules. The cellular and neurochemical composition of nodules was also examined using immunohistochemistry for calretinin and neuropeptide Y (NPY), which are normally expressed in GABAergic cortical interneurons. Within heterotopic nodules from all cases, numerous calretinin-positive neurons were identified, along with a few cell bodies and many processes positive for NPY. Calretinin-positive neurons within nodules were less morphologically complex than those in the cortex, which may reflect incomplete differentiation into an inhibitory neuronal phenotype. There were also abnormal clusters of calretinin-positive cells in the overlying cortical plate, indicating that the migratory defect which produces heterotopic nodules also affects development of the cortex itself. Thus, heterotopic nodules consisting of multiple neuronal cell types are associated with malformation in the overlying cortical plate, and have limited connectivity with other brain regions. This abnormal development of connectivity may affect neuronal maturation and consequently the balance of excitation and inhibition in neuronal circuits, leading to their epileptogenic potential.

Brain Chemistry↗

N-Acetylcysteine treatment to prevent the progression of multisystem organ failure: a prospective, randomized, placebo-controlled study.

OBJECTIVES: To investigate whether prolonged infusion of N-acetylcysteine (NAC) that is commenced immediately after admission to the intensive care unit could ameliorate the development or progression of multisystem organ failure and improve mortality. DESIGN: Prospective, randomized, double-blinded clinical trial. SETTING: Six-bed intensive care unit in a teaching hospital. PATIENTS: Of the 100 patients recruited (14 withdrew), 86 patients were studied. INTERVENTIONS: After randomization, the treatment group (n = 41) received NAC (150 mg/kg bolus followed by a continuous infusion of 12 mg/kg/hr) and the placebo group (n = 45) received 5% dextrose, from a minimum of 3 days up to a maximum of 5 days. MEASUREMENTS AND MAIN RESULTS: There was no statistically significant difference between the two groups regarding outcome as indicated by mortality and the required days of inotropic support, mechanical ventilation, and intensive care. The time interval between hospital and intensive care unit admission showed great variability, with a median of 24 hrs for the whole sample. By splitting the groups with this median value, the effect of NAC was examined on patients admitted within 24 hrs and after 24 hrs of arrival to the hospital. There was a nonsignificant difference in mortality in favor of NAC. Patients admitted after 24 hrs of hospital admission had a significantly worse mortality in the NAC-treated group (61% vs. 32% for controls; p = .05). CONCLUSIONS: We found a nonsignificant difference in outcome between NAC and placebo-treated patients. Our results suggest that the initiation of NAC treatment >24 hrs after hospital admission may potentially be harmful, and further studies should be undertaken to investigate the clinical use of the early application of NAC in critically ill patients.

APACHE↗

Sedation for ambulatory endoscopy.

Diagnostic and therapeutic fiberoscopy of gastrointestinal tract is often performed ambulatory and sedation is sometimes also required. Indication for sedation can be the intervention itself or the patient's psychological state. Aim of the study was to compare the effects of midazolam and combination of midazolam and fentanyl during endoscopy. Twenty eight cases were investigated: oesophagogastroduodenoscopy (n = 14) and colonoscopy (n = 14). Anaesthetics were midazolam (M) in 16 cases, midazolam-fentanyl (MF) in 12 cases. Non-invasive mean arterial pressure, pulse rate, acid-base balance and blood gases (by Astrup method) were recorded before endoscopy, at the 5th and 10th minutes of endoscopy, 15 minutes after intervention and also before emission. Pulse rate changed between 78-92/min. Mean arterial pressure appeared between 84-90 mm Hg. In MF group both were lower but there was not significant difference between the groups. The values were in normal range, there were not metabolic acidosis which needed correction. Onset of sedative effect was 2.8 min. in M group, 2.3 min. in MF group. The ability for adequate reaction returned within 11 min. in M group, within 14 min. in MF group. Fentanyl prolongs sedative effect of midazolam and offers sufficient pain relief. After 3 hours, patients could be emitted from the hospital.

Acid-Base Equilibrium↗

Development of thalamocortical projections in the South American gray short-tailed opossum (Monodelphis domestica).

We determined the time-course and general pattern of thalamocortical development of Monodelphis domestica by tracing projections with carbocyanine dye in fixed postnatal brains between postnatal day 2 (P2) and P30. By P2, the first neurons have migrated to form the preplate of the lateral cortex and have sent out axons into the intermediate zone. By P3, fibers from the preplate of more dorsal cortex have entered the intermediate zone, and, by P5, they reach the primitive internal capsule. Crystal placements in the dorsal thalamus at P2-P3 reveal thalamic axons extending down through the diencephalon and growing out through the internal capsule among groups of back-labelled cells that already project into the thalamus. Thalamic axons arrive at the cortex after the arrival of cells of the true cortical plate has split the preplate into marginal zone and subplate. Axons from the ventral part of the dorsal thalamus reach the lateral cortex by P5: Dorsal thalamic fibers arrive at the extreme dorsal cortex by P9. The deeper layers of the cortex appear to mature relatively earlier in Monodelphis than in eutherian mammals, and the subplate becomes less distinct. Thalamic fibers and their side branches proceed into the cortex without an obvious period of waiting in the subplate, but they do not penetrate the dense cortical plate itself. Monodelphis could provide an excellent model species, because the development of its thalamocortical connections is entirely an extrauterine process: The period P0-P15 corresponds to that of E12-P0 in the rat.

Animals↗

Mechanisms underlying the early establishment of thalamocortical connections in the rat.

We labeled axonal projections using carbocyanine dyes in the developing rat brain to study cellular interactions that might underlie the establishment of thalamocortical connectivity. By embryonic day 14 (E14), groups of neurons in the ventral diencephalon and the primitive internal capsule have established projections to the dorsal thalamus, and thalamic fibers pass in topographic order among them. Simultaneously, axons from the early-born cells in both subplate and marginal zone (i.e., the original cortical preplate) establish an ordered array that fills the intermediate zone. Thalamic axons and preplate fibers meet in the lateral part of the internal capsule (at E15 for occipital cortex and dorsolateral thalamus). Subsequently, selective labeling of corresponding thalamic and early corticofugal projections reveals thalamic fibers growing in association with early corticofugal axons, right up to the cortical subplate. A small carbocyanine crystal implanted at any point in the cortex shortly after the arrival of thalamic axons (E16 for the occipital cortex) labels a single, tight bundle containing both descending and ascending fibers, rather than two separate tracts, providing further evidence for intimate topographic association of the two axon systems. Crystals placed in a row, parasagittally or coronally along the hemisphere, reveal separate, topographically distributed, discrete fiber bundles throughout the pathway, leading to spatially ordered groups of back-labeled thalamic cells. These results indicate that the topography of thalamic axons is maintained throughout the pathway and that they reach the cortex by associating with the projections of a number of preexisting cells, including the preplate scaffold.

Animals↗

The role of the first postmitotic cortical cells in the development of thalamocortical innervation in the reeler mouse.

In the mutant mouse reeler, the tangential distribution of thalamocortical fibers is essentially normal, even though neurons of the cortical plate accumulate below the entire early-born preplate population (Caviness et al., 1998). This seems incompatible with the hypothesis that cells of the subplate (the lower component of the preplate in normal mammals) form an axonal scaffold that guides thalamic fibers and act as temporary targets for them (Blakemore and Molnár, 1990, Shatz et al., 1990). We used carbocyanine dyes to trace projections in wild-type and reeler mice between embryonic day 13 and postnatal day 3. Preplate formation and early extension of corticofugal fibers to form a topographic array are indistinguishable in the two phenotypes. So too are the emergence of thalamic axons in topographic order through the primitive internal capsule, their meeting with preplate axons, and their distribution over the preplate scaffold. Distinctive differences appear after the cortical plate begins to accumulate below the preplate of reeler, causing the preplate axons to form oblique fascicles, running through the cortical plate. Thalamic axons then pass through the plate within the same fascicles and accumulate in the "superplate" layer for approximately 2-3 d, before defasciculating and plunging down to terminate deep in the cortical plate, creating the curious "looping" pattern seen in the adult. Thus, thalamocortical innervation in reeler follows the same algorithm of development but in relation to the misplaced population of early-born neurons. Far from challenging the theory that preplate fibers guide thalamic axons, reeler provides strong evidence for it.

Animals↗

[The role of elective hemofiltration in the management of sepsis and multiple organ failure].

Septic shock and the multiple organ dysfunction syndrome carries a very high risk of mortality. The exact pathomechanism of the development of multiorgan dysfunction is yet to be revealed and its treatment remains the biggest challenge in intensive care. In order to prevent the development of multiple organ dysfunction new therapeutic modalities have been investigated over the last years. One promising intervention is the exchange of large volumes of ultrafiltrate during haemofiltration termed as "elective" haemofiltration. By removing several middle molecular weight inflammatory mediators from the circulation, currently thought to be responsible for a number of complications due to sepsis, it as been suggested, that it might improve survival in theses patients.

Female↗

Anaesthesiological indications and contraindications of minimally invasive surgery.

Spreading of laparoscopic techniques caused changes in anaesthesiological contraindications. In the first period laparoscopy was contraindicated in ischemic heart disease (IHD). Early mobilisation and short postoperative period are positive goals, IHD was taken out of contraindications. Present study compares changes in circulatory, blood gas and acid-base balance values during laparoscopic cholecystectomy (LC) in groups of patients ASA I-II. and ASA III. with IHD. There were 30 patients in group ASA I-II, 30 patients with IHD in category of ASA III. investigated during LC. Fifteen patients of both groups went under Propofol-Fentanyl (TIVA) anaesthesia, others were on Propofol-Fentanyl-N2O (IVA) protocol. All of them got also Atracurium. Pulse rate, mean arterial pressure, O2 saturation and end tidal CO2, blood gases and acid-base state were recorded before induction, after CO2 insufflation, after desufflation, 1 and 3 hours postoperatively. After CO2 insufflation there was a moderate tachycardia in both ASA III. groups (74/min-->88/min). In all groups pCO2 increased (40-->48 mmHg) but normalised till the 3rd postoperative hours (42 mmHg). Ventricular extrasystoles appeared in 3 ASA III. patients in IVA group. Three high risk patients had serious metabolic acidosis postoperatively. Present time the ischaemic heart disease does not contraindicates laparoscopic interventions. TIVA with Propofol is better choice because of its favourable effects on circulation and acid-base balance. Using N2O caused higher grade of intestinal distension. The cardio-respiratory, blood gas parameters and acid-base balance have to be monitorised in perioperative period of laparoscopic surgery.

Acid-Base Equilibrium↗

ABVD chemotherapy of Hodgkin's disease.

The authors report on their results in ABVD therapy, which was given by 91 patients with Hodgkin's disease as first-line treatment. 78 patients (85% achieved complete, 10 (11%) partial remission, 3 (4%) did not respond to therapy. In the follow-up period (36-223 months) 6 patients (7%) died because of the progression of Hodgkin's disease. Serious side effects or treatment-related death did not occur. Based on their results of ABVD, the authors find ABVD chemotherapy effective as first-line treatment of Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗

[Significance of ST segment and R wave changes in exercise-induced supraventricular extrasystole].

In a retrospective study the importance of ST segment and R wave changes in sinus beats and in supraventricular extrasystoles was examined in 23 patients who had exhibited supraventricular extrasystoles during exercise testing and who had undergone coronary arteriography in 1993 and 1994. Significant coronary artery disease was detected in 18 patients (group A), whereas 5 subjects (group B) had no demonstrable obstructive lesions. In every patient the authors measured the ST depression and R wave amplitude of the supraventricular extrasystole (STe and Re, respectively), and of the preceding sinus beat (STs and Rs, respectively), and than they calculated the difference between the two [ST(e-s) and R(e-s), respectively]. The ST(e-s) + R(e-s) value was higher than zero mV in 13 patients in group A, and in neither case in group B. Among the 4 patients in group A with false negative results of exercise tests, 3 had a positive ST(e-s) + R(e-s) value, whereas the only patient in group B with false positive exercise test result had a negative ST(e-s) + R(e-s) value. In patients with exercise induced supraventricular extrasystoles, the changes of ST depression and R wave amplitude in the extrasystoles and in the preceding sinus beats, may supplement the criterions of a positive examination.

Arrhythmia, Sinus↗

Influence of the pathological psychological state of cancer patients on their decisions.

The diagnosis of cancer in many cases provokes a crisis, resulting in an increase of regression and defence mechanisms (splitting, projective identification, projection, denial, repression). This article reviews the increased sensitivity, the partial and temporary narrowing of consciousness, and the weakening of reality control. In many cases fluctuating depersonalisation and derealisation develop. At our Institute we performed a complex psychological examination of 41 patients, suffering from malignant lymphoma, immediately after informing them of the diagnosis but prior to their first treatment. The psychological examination of volunteering patients involved an initial interview, Rorschach and Szondi projective tests, a Wechsler intelligence test and a discussion of the results with the patient. The relatively frequent temporary pathological psychic conditions exert an influence on the decisions of patients make about their treatment and interventions, and may also influence the doctor patient relationship.

Adolescent↗

[Second malignant disease in patients under treatment for malignant lymphoma].

Between 1978 and 1993, 1013 patients 529 with Hodgkin's disease and 484 with non-Hodgkin's lymphomas--were treated in our department. Out of 1013 patients secondary neoplasms developed in 23 cases: 3 acute nonlymphocytic leukemia, 19 solid tumors and 1 secondary non-Hodgkin's lymphoma. The median time from diagnosis of malignant lymphoma was 7 years and their median age was 49 years. 11 patients with secondary tumor were treated with chemotherapy and 12 received combined (radio- and chemo-) therapy. Since alkylating agents increase the risk of leukemia and radiation contributes mainly to other cancer, future treatment protocols should attempt to reduce the most serious consequences of therapy without compromising the survival. Careful lifelong observation is indicated for patients with malignant lymphomas, with special attention given to new clinical signs or symptoms.

Adult↗

Guidance of thalamocortical innervation.

We propose that a sequence of individually simple mechanisms influences the pattern of thalamocortical innervation, which itself contributes to the determination of regional differentiation of the neocortex. In co-culture, the cortex appears to exert a remote growth-promoting influence on thalamic axons from E15, becomes growth-permissive to axon invasion at about E20 and expresses a stop signal, causing termination in layer IV, from P2-3. This cascade of cortical signals may determine the timing of events in vivo. However, any part of the thalamus will innervate any region of the developing cortex in culture, without obvious preference, suggesting that the topographic distribution of thalamic fibres in vivo does not depend on regional chemospecificity. The initial extension of axons from the cortical preplate and the thalamus starts at about E14, and the topography of both may be influenced by their temporal sequences of outgrowth (chronotopy). The axon arrays meet in the basal telencephalon, after which the preplate scaffold may guide thalamic axons and ensure both their 'capture' within the subplate layer and the establishment of the waiting period. The unusual pattern of innervation in the Reeler mutant mouse supports the hypothesis that thalamic axons grow over preplate fibres to find the waiting compartment.

Animals↗

How do thalamic axons find their way to the cortex?

A cascade of simple mechanisms influences thalamic innervation of the neocortex. The cortex exerts a remote growth-promoting influence on thalamic axons when they start to grow out, becomes growth-permissive when the axons begin to invade, and later expresses a 'stop signal', causing termination in layer 4. However, any part of the thalamus will innervate any region of developing cortex in culture, and the precise topographic distribution of thalamic fibres in vivo is unlikely to depend exclusively on regional chemoaffinity. The 'handshake hypothesis' proposes that axons from the thalamus and from early-born cortical preplate cells meet and intermingle in the basal telencephalon, whereafter thalamic axons grow over the scaffold of preplate axons, and become 'captured' for a waiting period in the subplate layer below the corresponding part of the cortex. The bizarre pattern of development of thalamic innervation in the mutant reeler mouse provides strong evidence that thalamic axons are guided by preplate axons.

Animals↗

[CHOP-Bleo therapy in high-malignancy non-Hodgkin lymphoma].

The records of 85 patients were reviewed in order to study the efficacy of CHOP-Bleo combination chemotherapy and to determine factors influencing prognosis. The patients were treated between 1978 and 1989, the median age was 44.4 (range, 15-68) years, the majority of them were in advanced clinical stages (92.9%). Systemic (B) symptoms were present in half of the patients and a quarter of them had bulky disease. Complete response was achieved in 36 patients (42.5%), partial response in 26 patients (30.5%), and primary treatment failure occurred in 23 patients (27.0%). The median survival was 92.6 months and 36.5% of the patients remained relapse-free at 10 years. The expected 5-year and 10-year survival rates were 47% and 39%, respectively. Using multivariate analysis B symptoms, involvation of two or more extralymphatic sites and lymphoblastic histologic subtype proved to be unfavourable prognostic factors. The most frequently observed side-effects were myelosuppression, neurotoxicity and gastrointestinal symptoms. No treatment-related death have occurred.

Adolescent↗

[Initial results of hybrid chemotherapy of Hodgkin's disease using COPP/VBA].

19 patients with advanced, previously untreated Hodgkin's disease were treated with COPP/ABV (cyclophosphamide, vincristine, procarbasine, prednisolone, adriamycin, bleomycine, vinblastine) hybrid regimen. Complete response was achieved in 8 patients, partial response in 9 patients and primary treatment failure occurred in 2 patients. Two patients received involved field irradiation for the residual disease. 17 months after finishing the therapy one of the complete responders suffered a relapse. Of the 8 partial responders, 5 patients relapsed. 2 relapses occurred during the treatment and 3 relapses were observed in the first 7 months of follow-up. 2 of the partial responders and both nonresponders succumbed to their disease. There were no serious side effects and treatment-related death did not occur.

Antineoplastic Combined Chemotherapy Protocols↗