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Biomedical subjects

P Molnar

Publications and source records attributed to P Molnar.

At least 19 recordsLinked to original sources

Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.

The threat of environmental pollution, biological warfare agent dissemination and new diseases in recent decades has increased research into cell-based biosensors. The creation of this class of sensors could specifically aid the detection of toxic chemicals and their effects in the environment, such as pyrethroid pesticides. Pyrethroids are synthetic pesticides that have been used increasingly over the last decade to replace other pesticides like DDT. In this study we used a high-throughput method to detect pyrethroids by using multielectrode extracellular recordings from cardiac cells. The data from this cell-electrode hybrid system was compared to published results obtained with patch-clamp electrophysiology and also used as an alternative method to further understand pyrethroid effects. Our biosensor consisted of a confluent monolayer of cardiac myocytes cultured on microelectrode arrays (MEA) composed of 60 substrate-integrated electrodes. Spontaneous activity of these beating cells produced extracellular field potentials in the range of 100 microV to nearly 1200 microV with a beating frequency of 0.5-4 Hz. All of the tested pyrethroids; alpha-Cypermethrin, Tetramethrin and Tefluthrin, produced similar changes in the electrophysiological properties of the cardiac myocytes, namely reduced beating frequency and amplitude. The sensitivity of our toxin detection method was comparable to earlier patch-clamp studies, which indicates that, in specific applications, high-throughput extracellular methods can replace single-cell studies. Moreover, the similar effect of all three pyrethroids on the measured parameters suggests, that not only detection of the toxins but, their classification might also be possible with this method. Overall our results support the idea that whole cell biosensors might be viable alternatives when compared to current toxin detection methods.

Action Potentials↗

Closing of the Indonesian seaway as a precursor to east African aridification around 3-4 million years ago.

Global climate change around 3-4 Myr ago is thought to have influenced the evolution of hominids, via the aridification of Africa, and may have been the precursor to Pleistocene glaciation about 2.75 Myr ago. Most explanations of these climatic events involve changes in circulation of the North Atlantic Ocean due to the closing of the Isthmus of Panama. Here we suggest, instead, that closure of the Indonesian seaway 3-4 Myr ago could be responsible for these climate changes, in particular the aridification of Africa. We use simple theory and results from an ocean circulation model to show that the northward displacement of New Guinea, about 5 Myr ago, may have switched the source of flow through Indonesia-from warm South Pacific to relatively cold North Pacific waters. This would have decreased sea surface temperatures in the Indian Ocean, leading to reduced rainfall over eastern Africa. We further suggest that the changes in the equatorial Pacific may have reduced atmospheric heat transport from the tropics to higher latitudes, stimulating global cooling and the eventual growth of ice sheets.

Africa, Eastern↗

Increased sedimentation rates and grain sizes 2-4 Myr ago due to the influence of climate change on erosion rates.

Around the globe, and in a variety of settings including active and inactive mountain belts, increases in sedimentation rates as well as in grain sizes of sediments were recorded at approximately 2-4 Myr ago, implying increased erosion rates. A change in climate represents the only process that is globally synchronous and can potentially account for the widespread increase in erosion and sedimentation, but no single process-like a lowering of sea levels or expanded glaciation-can explain increases in sedimentation in all environments, encompassing continental margins and interiors, and tropical as well as higher latitudes. We suggest that climate affected erosion mainly by the transition from a period of climate stability, in which landscapes had attained equilibrium configurations, to a time of frequent and abrupt changes in temperature, precipitation and vegetation, which prevented fluvial and glacial systems from establishing equilibrium states.

Journal Article↗

Patient education in Hungary.

Patient education is a highly context dependent activity. The Hungarian scene is conditioned by three well articulated aspects. First, the well developed and still cherished roots of dissemination of knowledge; second, the traditional sensitivity of ethical issues in health related, including death and dying issues; third, the present fast socio-political changes in this country. The health promoting hospital movement's widespread activities as well as behavioral sciences, mental health and health psychology aspects of patient education are also reviewed. The theoretical as well as skills aspects of communication and systematic attempts to increase the effectiveness of interactions are also presented.

History, 20th Century↗

Continuous deformation versus faulting through the continental lithosphere of new zealand

Seismic anisotropy and P-wave delays in New Zealand imply widespread deformation in the underlying mantle, not slip on a narrow fault zone, which is characteristic of plate boundaries in oceanic regions. Large magnitudes of shear-wave splitting and orientations of fast polarization parallel to the Alpine fault show that pervasive simple shear of the mantle lithosphere has accommodated the cumulative strike-slip plate motion. Variations in P-wave residuals across the Southern Alps rule out underthrusting of one slab of mantle lithosphere beneath another but permit continuous deformation of lithosphere shortened by about 100 kilometers since 6 to 7 million years ago.

Journal Article↗

Microvessel organization and structure in experimental brain tumors: microvessel populations with distinctive structural and functional properties.

We studied microvessel organization in five brain tumor models (ENU, MSV, RG-2, S635cl15, and D-54MG) and normal brain, including microvessel diameter (LMVD), intermicrovessel distance (IMVD), microvessel density (MVD), surface area (S(v)), and orientation. LMVD and IMVD were larger and MVD was lower in tumors than normal brain. S(v) in tumors overlapped normal brain values and orientation was random in both tumors and brain. ENU and RG-2 tumors and brain were studied by electron microscopy. Tumor microvessel wall was thicker than that of brain. ENU and normal brain microvessels were continuous and nonfenestrated. RG-2 microvessels contained fenestrations and endothelial gaps; the latter had a maximum major axis of 3.0 microm. Based on anatomic measurements, the pore area of RG-2 tumors was estimated at 7.4 x 10(-6) cm(2) g(-1) from fenestrations and 3.5 x 10(-5) cm(2) g(-1) from endothelial gaps. Increased permeability of RG-2 microvessels to macromolecules is most likely attributable to endothelial gaps. Three microvessel populations may occur in brain tumors: (1) continuous nonfenestrated, (2) continuous fenestrated, and (3) discontinuous (with or without fenestrations). The first group may be unique to brain tumors; the latter two are similar to microvessels found in systemic tumors. Since structure-function properties of brain tumor microvessels will affect drug delivery, studies of microvessel function should be incorporated into clinical trials of brain tumor therapy, especially those using macromolecules.

Animals↗

Heart rate deceleration during the grasping reflex.

UNLABELLED: Heart rate changes were measured as a psychophysiological indicator during grasping reflex in 27 full-term healthy newborns at 2.5-50 h after birth. A significant heart rate deceleration accompanied the grasping response. CONCLUSION: Reflex grasping of a mother's hand, as a component of human attachment behaviour, may have a positive calming effect on the infant's state and could have therapeutic value for high risk mother-infant dyads.

Electrocardiography↗

Absence of host-site influence on angiogenesis, blood flow, and permeability in transplanted RG-2 gliomas.

The host site is believed to regulate tumor angiogenesis, which could result in site-dependent drug delivery parameters, greatly affecting experimental tumor research. In RG-2 rat gliomas we measured cellular proliferation; cell cycle time was the same for RG-2 cells in brain and s.c. tumors (25 h), and was the same for endothelial cells in these tumors (46 h). We measured the transcapillary transfer constant (K) of alpha-aminoisobutyric acid and blood flow (F) with iodoantipyrine in RG-2 gliomas transplanted into brain, liver, kidney, muscle, s.c. tissue, and into the abdominal cavity. Data was evaluated by quantitative autoradiography and direct tissue sampling. The variation of F (12.6-84.0 ml/g/min) and K (26.1-49.2 microl/g/min) in RG-2 tumors in the different host sites was less than in surrounding tumor-free tissue (F = 20-1500 ml/g/min and K = 1.6-700 microl/g/min). In contrast to other models, RG-2 does not result in tumors with host site-dependent behavior. The RG-2 tumor cells appear to participate in, if not dominate, the angiogenesis process regardless of the host site. Values of F and K were more dependent on tumor topography (center versus periphery) and local histological features (necrosis versus viable tumor) than host site. We believe that the methods used for data acquisition may introduce as much variability in Results as the tumors themselves and that to better understand how tumor angiogenesis affects the vascular phenotype, comparative studies are needed to validate the results obtained with newer methodologies.

Algorithms↗

Simultaneous continuous measurement of pO2, pCO2, pH and temperature in brain tissue and sagittal sinus in a porcine model.

INTRODUCTION: The clinical use of brain tissue oxygen measurement in patients with severe head injury is increasing. It is important to compare the findings in brain tissue with cerebrovenous blood oximetry, to obtain normal values and to find out limitations of the method. We evaluated a newly available multisensor probe simultaneously in the brain tissue and in the sagittal sinus in a porcine animal model. METHODS: We placed the Paratrend 7-probe (BSL, High Wycombe, UK) in the left frontoparietal white matter and measured pO2 (PtiO2), pCO2 (ptiCO2), pH and temperature while simultaneously measuring these parameters (pcvO2, pcvCO2) in the sagittal sinus in 7 pigs under general anaesthesia during oxygen enhancement. RESULTS: The relation between oxygen increase in brain tissue and in the sagittal sinus showed a coefficient of correlation (CCmean) rmean = 0.96. The quantitative response in brain tissue was much more sensitive than in the sinus. A close correlation between pCO2 in brain tissue and sagittal sinus and the increase of the inspired oxygen was seen: CC ptiCO2 to arterial oxygen pressure (paO2) - rmean = 0.67, CC pcvCO2 to paO2 - rmean = 0.88. CONCLUSIONS: Measuring partial oxygen pressure in brain tissue is more responsive to physiological variations, and the absolute values are more sensitive than oxygen measurement in the cerebrovenous compartment. This is important for interpreting measured values and introducing new coefficients for patient monitoring.

Acid-Base Equilibrium↗

Temperature of the cerebrovenous blood in a model of increased intracranial pressure.

UNLABELLED: Hypothermia has a considerable protective effect during brain ischemia. On the other hand small increases of brain temperature have a remarkable effect on the exacerbation of neurological damage following an ischemic event. Hyperthermia of the brain tissue after severe head injury is described. The effect of acutely increased intracranial pressure on cerebrovenous blood temperature is not described yet. The aim of this study was to investigate the relationship between temperature in the cerebrovenous compartment (Tcv) and changes of the CPP in an animal model of raised intracranial pressure. METHODS: A thermocouple was inserted in the sagittal sinus in 9 pigs under general anesthesia. By stepwise inflating a supracerebral and infratentorial placed balloon catheter intracranial pressure (ICP) was increased and CPP concomitantly decreased. The central body temperature was measured simultaneously in the abdominal aorta (Ta) with a second thermocouple. RESULTS: In our model th Tcv was lower than Ta at the beginning of the ICP increase. The mean difference between Ta and Tcv, (delta Ta-cv) was 0.86 degree C (+/- 0.44) prior to ICP increase and 1.19 degrees C (0.58) at the maximum ICP increase. Thus, delta Tav increased during CPP reduction. This relation was represented by an adjusted R(square) of r2 = 0.89 (p < 0.001). CONCLUSIONS: The CPP decrease, caused by an increasing ICP, results in changes of the cerebrovenous blood temperature. Interpreting the present results the experimental situation of a relative colder cerebral compartment in comparison to the central body temperature has to be considered. However, the results imply, that simultaneous temperature monitoring of the central body temperature and the cerebrovenous blood temperature is an additional source of information about relative changes of the CBF.

Animals↗

Comparison between continuous brain tissue pO2, pCO2, pH, and temperature and simultaneous cerebrovenous measurement using a multisensor probe in a porcine intracranial pressure model.

Local brain tissue oxygenation (p(ti)O2) and global cerebrovenous hemoglobin saturation (SjO2) are increasingly used to continuously monitor patients after severe head injury (SHI). In patients, simultaneous local and global oxygen measurements of these types have shown different results regarding the comparability of the findings during changes in CPP and ICP. This is in contrast to theoretical expectations. The aim of this study was to compare p(ti)O2 measurement with cerebrovenous oxygen partial pressure measurement (p(cv)O2) in an animal intracranial pressure model. To this end, a multisensor probe was placed in the left frontoparietal white matter to measure p(ti)O2, pCO2 (p(ti)CO2), pH (pH[ti]), and temperature (t[ti]) while simultaneously measuring these same parameters (p(cv)O2, p(cv)CO2 pH(cv), t[cv]) in the sagittal sinus of 9 pigs under general anesthesia. By stepwise inflating a balloon catheter, placed in supracerebellar infratentorial compartment, ICP was increased and CPP was decreased. The baseline levels of p(ti)O2, p(ti)CO2, and pH(ti) in the noninjured brain tissue showed more heterogeneity compared to the findings in cerebrovenous blood. Both, p(ti)O2 and p(cv)O2 were significantly correlated to the induced CPP decrease. PCO2 was inversely correlated to the course of CPP in both measurement compartments. Temperature measurement showed a positive correlation with CPP in both compartments. These findings demonstrate that brain tissue oximetry and cerebrovenous PO2 measurement are sensitive to CPP changes. The newly available continuous parameters in multisensor probes could be helpful in interpreting findings of cerebral oxygen measurement in man by analyzing the interrelationship of these parameters.

Anesthesia, General↗

Differential expression of tissue transglutaminase during in vivo apoptosis of thymocytes induced via distinct signalling pathways.

A significant increase in the expression and activity of tissue transglutaminase (tTG), one of the effector elements of apoptosis, was observed during involution of thymus elicited by treatment with either anti-CD3 antibody or dexamethasone or by irradiation. The blood plasma concentration of epsilon(gamma-glutamyl)lysine isodipeptide, the end-product of the digestion of transglutaminase cross-linked proteins, was also elevated in each of these cases. tTG was localized in cells of the cortical layer of the thymus and immunofluorescence double staining revealed that the enzyme appeared in the apoptotic cells. None of these observations could be made when apoptosis was induced by fas-receptor stimulation. The lack of tTG activity in fas-stimulated cells was accompanied with a less organized apoptotic morphology. Our data suggest that distinct signalling pathways, which induce apoptosis within the same cell type, can differentially regulate the expression of tTG, and this enzyme may be involved in structural stabilization of the apoptotic cells.

Animals↗

Can pregnant women obtain their own specimens for group B streptococcus? A comparison of maternal versus physician screening. The Mount Sinai GBS Screening Group.

OBJECTIVE: We aimed to compare the Group B Streptococcus (GBS) detection rate when pregnant women performed their own vaginal/anorectal swabs with that from the standard practice of physician-performed swabs. METHOD: The research involved a comparison of maternally obtained swabs for GBS with the current gold standard of physician-obtained swabs performed on the same patient. The women were surveyed about who they would prefer to do their swabs. This research was carried out in the offices of five family physicians and eight obstetricians at Mount Sinai Hospital, Toronto--a tertiary-care teaching hospital--between 1 November 1995 and 31 March 1996. The patients were consecutive pregnant women presenting for their 26-28 weeks antenatal visit. Patients were given a questionnaire and instructions describing how to perform a vaginal/anorectal swab. After each patient completed the survey and obtained her own GBS culture, the physician collected a GBS specimen in their usual manner. The main outcome measures were the results of self-performed and physician-obtained combined vaginal/anorectal culture specimens. RESULTS: Sixty-three matched pairs of GBS swab results and 161 patient surveys were collected. Using any positive result as the gold standard, the prevalence of GBS was 39 out of 163 (24%). Patients detected 38 cases for a sensitivity of 97% (lower 95% confidence limit 92), while physicians identified 32 cases for a sensitivity of 82% (95% confidence limit 70-94). Twenty-five per cent of the women preferred that the physician take the swab, while 75% were indifferent or preferred to self-swab. CONCLUSIONS: Patient-collected vaginal/anorectal swabs for GBS are at least as sensitive as the current practice of physician-performed swabs. The majority of participating patients were interested or willing to perform their own swab. Self-swabbing involves women more actively in their obstetrical care and may improve physician compliance with screening guidelines.

Adolescent↗

Expression of pituitary peptide 23 in the rat uterus: regulation by estradiol.

Peptide 23 was first identified in pituitary cell conditioned medium as a secreted protein which was regulated in a similar fashion to growth hormone. It was subsequently found to be a member of the C-type lectin gene superfamily and identical to pancreatis associated protein (PAP). It is widely expressed in the gastrointestinal tract. Our present study demonstrates that peptide 23 gene is also expressed in the uterus. Peptide 23/PAP mRNA was at highest levels during estrus and was not detectable in the immature rat uterus. A single injection of 17 beta-estradiol resulted in a transient induction of peptide 23/PAP mRNA in ovariectomized rats whereas a sustained induction was seen with diethylstilbestrol implants. In situ hybridization localized peptide 23/PAP mRNA to the luminal epithelial cells. During gestation, peptide 23/PAP mRNA was detected only in the uterine samples from day 12 to 18 of pregnancy with maximal expression on day 12. Peptide 23 expression was confined to the uterus itself and not expressed in either the decidua or the fetal tissues. PSP/reg, another closely related member of the C-lectin gene family was not expressed in any of these uterine tissues. These results indicate that estrogen may act as a physiological regulator of peptide 23 in the uterus and suggests that this protein may have some role in estrogen action.

Animals↗

The effects of dexamethasone on experimental brain tumors: I. Transcapillary transport and blood flow in RG-2 rat gliomas.

Dexamethasone dramatically improves cerebral edema associated with malignant gliomas. Although the pathophysiology of this effect is not clearly understood, many investigators have postulated that tumor capillary permeability is reduced by dexamethasone. We studied blood-to-tissue transport and blood flow in 178 RG-2 transplanted gliomas in a control group and four groups given dexamethasone at doses of 3, 6, 9, and 12 mg/kg for four days. 14C-alpha aminoisobutyric acid (AIB) was used to study blood-to-tissue transport in 31 animals; in an additional 27 animals 14C-AIB and 131I-iodoantipyrine (IAP) were used in double label experiments to study blood-to-tissue transport and blood flow. Regional measurements of the transfer constant (K) of AIB and blood flow (F) were made with quantitative autoradiography. There were significant differences between the control and dexamethasone-treated groups with regard to weight loss and plasma glucose. However, there was no significant effect of dexamethasone on values of K or F, regardless of the tumor or brain region examined, and regardless of the dose of dexamethasone administered. Analysis of the profiles of the transfer constant of AIB in the brain around tumor showed that the K of AIB decreased within 0.5 mm of the tumor edge in direct relationship to the dexamethasone dose. These results do not support the hypothesis that dexamethasone reduces brain tumor capillary permeability, and suggest that dexamethasone may decrease tumor-associated cerebral edema by effects on bulk flow away from the tumor margin.

Aminoisobutyric Acids↗

The effects of dexamethasone on transcapillary transport in experimental brain tumors: II. Canine brain tumors.

We studied the effect of dexamethasone on transcapillary transport in ten Avian Sarcoma Virus (ASV)-induced canine brain tumors, before and one week after administration of dexamethasone, 2.5 mg/kg/day. A computed tomographic (CT) method was used to measure regional values of K1 (blood-to-tissue transfer constant), k2 (tissue-to-blood efflux constant), and Vp (tissue plasma vascular space) of meglumine iothalamate (Conray-60); the values were reconstructed for each 0.8 x 0.8 x 5 mm volume element of the CT data. For all tumors considered together, there was a decrease in the whole tumor K1 value of meglumine iothalamate from 26 +/- 2.2 (SE) before dexamethasone to 24 +/- 2.9 microliters/g/min after dexamethasone. Vp decreased from 7.2 +/- 0.7 to 6.7 +/- 0.9 ml/100 g, and the size of the tumor extracellular space (Ve) decreased from 0.30 to 0.26 ml/g. These changes were not statistically significant. However, when each tumor was used as its own control, K1 significantly decreased after dexamethasone in four tumors, significantly increased in two and was unchanged in four. These results suggest that decreased blood-to-tissue transport may be one mechanism underlying resolution of tumor associated cerebral edema in some brain tumors and that the effects of dexamethasone on blood-to-tissue transport in brain tumors are variable from one tumor to the next. Decreased 'permeability' may not be the sole mechanism by which dexamethasone reduces tumor-associated cerebral edema.

Animals↗