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Biomedical subjects

S Mahon

Publications and source records attributed to S Mahon.

At least 19 recordsLinked to original sources
PubMed2001

Dendritic arborizations of the rat substantia nigra pars reticulata neurons: spatial organization and relation to the lamellar compartmentation of striato-nigral projections.

The cerebral cortex provides a major source of inputs to the basal ganglia. As has been well documented, the topography of corticostriatal projections subdivides the striatum into a mosaic of functionally distinct sectors. How information flow from these striatal sectors remains segregated or not within basal ganglia output nuclei has to be established. Electrophysiologically identified neurons of the rat substantia nigra pars reticulata were labeled by juxtacellular injection of Neurobiotin, and the spatial organization of their dendritic arborizations was analyzed in relation to the projection fields of individual striatal sectors. Thirty-nine nigral neurons located in the projection territory of the distinct striatal sensorimotor sectors were reconstructed. The data show that the dendritic arborizations of nigral neurons conform to the geometry of striato-nigral projections. Like striatal projections, the arborizations formed a series of curved laminas enveloping a dorsolaterally located core. Although dendritic fields of the neurons lying in the laminae were flat, those located in the core were spherical or cylindrical, thereby conforming to the shape of the striatal projection fields. This remarkable alignment between the dendritic arborizations of nigral neurons and the projection fields from individual striatal districts supports the concept of a parallel architecture of the striato-nigral circuits. However, pars reticulata neurons usually extend part of their dendrites within adjacent striatal projection fields, thereby ensuring a continuum between channels. The extension of the dendritic arborizations within the striatal projection fields suggests that nigral neurons integrate the information that is relevant for the completion of the specific motor behavior they control.

Action Potentials↗
PubMed2001

Screening high-risk populations for thyroid cancer.

BACKGROUND: Children treated with radiotherapy to the neck or exposed to environmental radiation are at risk for developing thyroid cancer later in life. The best method for screening these high-risk patients is unclear. We systematically reviewed evidence on the accuracy of ultrasound and palpation to detect thyroid nodules and of fine needle aspiration (FNA), a confirmatory test, to diagnose thyroid cancer. PROCEDURE: We searched the MEDLINE database for papers published since 1966, using the MeSH term thyroid neoplasms and terms related to diagnostic test performance. To supplement our MEDLINE searches, we searched reference lists from recent reviews and articles recommended by thyroid cancer experts. We recorded the tests used, the gold standard determination of disease, the test performance results, and the presence of biases that could affect the reported results. We also abstracted the number of patients who underwent surgery and the final diagnoses. We created two decision models: one for screening 10,000 medically irradiated patients, and one for screening 10,000 environmentally irradiated patients. RESULTS: Using ultrasound as the gold standard determination of the presence of a nodule, the sensitivity of palpation for all sized nodules was 10-41 percent, indicating that a high proportion of nodules detected by ultrasound are too small to be palpated. Sensitivity of palpation increased with nodule size. The specificity of palpation ranged from 95 to 100%. In studies from referral centers, the reported sensitivity and specificity of FNA were 71-95 and 52-99%, respectively. However, most authors excluded the proportion of patients (6-33%) who had inadequate or nondiagnostic FNA results when calculating sensitivity and specificity, even though 6-100% of these patients went on to have a diagnostic lobectomy. When each study was reanalyzed so that patients with nondiagnostic FNA results who went directly to surgery were reclassified as positive tests, sensitivity increased slightly, but specificity dropped by 4-20 percentage points per study. The decision model for screening 10,000 medically irradiated patients revealed that if ultrasound were used as an initial screen, 2,741 patients would have nodules at least 1 cm in size; assuming no patients with smaller nodules had surgery, 1,964 patients would have surgery; 275 patients would have a diagnosis of thyroid cancer. Screening with ultrasound as an initial test would detect an additional 150 cases of thyroid cancer compared to those screened with palpation. However, an additional 1,689 patients would have surgery for nonmalignant nodules (compared to 480 patients with nonmalignant nodules screened with palpation). The yield for screening 10,000 environmentally irradiated patients was several times smaller than for screening 10,000 medically irradiated patients. If 10,000 environmentally irradiated patients were screened initially with ultrasound, approximately 708 patients would have nodules at least 1 cm in size; 89 patients would have surgery; and 38 patients would be diagnosed with thyroid cancer. CONCLUSIONS: Regardless of type of exposure, testing initially with ultrasound detects several times more cases of thyroid cancer than palpation. However, when ultrasound is the initial test, many more patients also have surgery for nonmalignant nodules. Screening with palpation is not very reassuring, particularly to medically irradiated patients with negative tests, since almost half (46%) of these patients may have undetected nodules.

Decision Support Techniques↗
PubMed2001

Exploration of xenon as a potential cardiostable sedative: a comparison with propofol after cardiac surgery.

Xenon anaesthesia is thought to have minimal haemodynamic side-effects. It is, however, expensive and requires special delivery systems for economic use. In this randomised cross-over study, we: (i) investigated the haemodynamic profile and recovery characteristics of xenon compared with propofol sedation in postoperative cardiac surgery patients, and (ii) evaluated a fully closed breathing system to minimise xenon consumption. We demonstrated a significantly faster recovery from xenon (3 min 11 s) than propofol sedation (25 min 23 s). Relative to propofol, xenon sedation produced no change in heart rate or mean arterial pressure and there were significantly higher mean values for central venous pressure (10.6 vs. 8.9 mmHg), pulmonary artery occlusion pressure (11.2 vs. 9.5 mmHg), mean pulmonary artery pressure (20.1 vs. 18.3 mmHg) and systemic vascular resistance index (2170 vs. 1896 dyn.s.cm-5.m-2). The haemodynamic profile seen with propofol reflected its known vasodilator effects. This was supported by the almost identical left ventricular stroke work indexes seen with both methods of sedation.

Aged↗
PubMed2001

Relationship between EEG potentials and intracellular activity of striatal and cortico-striatal neurons: an in vivo study under different anesthetics.

The functions of the basal ganglia are achieved through excitation of striatal output neurons (SONs) by converging cortical glutamergic afferents. We assessed the relationship between different patterns of activity in cortico-striatal (C-S) cells and the electrical behavior of SONs in vivo. Intracellular activities of rat C-S neurons in the orofacial motor cortex and of SONs, located in the projection field of this cortical region, were recorded under different anesthetics, which generate various temporal patterns of cortical activity. A surface electroencephalogram (EEG) of the orofacial motor cortex was simultaneously performed with intracellular recordings and EEG waves were used as correlates of a coherent synaptic activity in cortical neurons. Under barbiturate anesthesia C-S neurons showed rhythmic (5--7 Hz) supra-threshold depolarizations in phase with large amplitude EEG waves. The correlative activity of SONs was characterized by large amplitude oscillation-like synaptic depolarizations that could trigger action potentials. Under ketamine-xylazine anesthesia C-S neurons exhibited a step-like behavior consisting of depolarizing plateaus (up states), leading to multiple spike discharges, interrupted by hyperpolarizing periods (down states). The related activity of SONs was step-like membrane potential fluctuations with firing confined to the early part of the striatal up state. In C-S neurons and SONs up states coincided with slow recurrent EEG waves (approximately 1 Hz). Finally, under neurolept-analgesia an apparently disorganized EEG activity was associated with a lack of rhythmic discharge in C-S neurons. This uncorrelated activity in C-S neurons resulted in an absence of spontaneous firing as well as of large amplitude synaptic depolarizations in SONs. In the present study we demonstrate that SONs shape their input-output relationship by filtering out uncorrelated synaptic activity and that a minimal synchronization in the cortico-striatal afferents is required to produce significant synaptic depolarization in SONs.

Action Potentials↗
PubMed2000

Anaesthetic management of caesarean section in a patient with a permanent pacemaker and severe bilateral ventricular dilatation.

A 33-year-old primigravida presented at 32 weeks gestation with increasing shortness of breath related to left ventricular failure. She had severe bilateral ventricular dilatation of unknown aetiology. An urgent caesarean section was required when she failed to improve on medical therapy, and for this she requested general anaesthesia. The patient had a permanent pacemaker for congenital complete heart block and Harrington rods for kyphoscoliosis. In view of the cardiac problems we transferred the patient to our cardiac unit and performed the procedure with full invasive haemodynamic monitoring. An alfentanil based modified rapid sequence induction resulted in stable maternal haemodynamics. The 2.2 kg male neonate initially required ventilation for 12 h, but then made a good recovery along with his mother.

Journal Article↗
PubMed2000

Use of nitric oxide for decompensated right ventricular failure and circulatory shock after cardiac arrest.

We describe a case of peri-operative cardiac arrest, severe right ventricular failure and pulmonary hypertension in a 60-yr-old woman with interstitial pulmonary fibrosis. Inhaled nitric oxide therapy rapidly improved arterial oxygenation and haemodynamic variables, allowing recovery and weaning from mechanical ventilation. Subsequently, the patient was discharged from the cardiac intensive care unit.

Anesthesia, General↗
PubMed1999

On the putative contribution of GABA(B) receptors to the electrical events occurring during spontaneous spike and wave discharges.

Cortical and thalamic neurones play a major role in the generation/expression of spike and wave discharges (SWDs), the main electroencephalographic (EEG) feature of absence seizures. The detailed mechanisms leading to this paroxysmal EEG activity, however, are still poorly understood. We have now made in vivo intracellular recordings from layer V cortical neurones of the facial motor cortex and from thalamocortical (TC) neurones of the ventroposteromedial and ventroposterolateral nuclei in a well established model of this disease: the Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The main feature of the intracellularly recorded activity of TC neurones during spontaneous SWDs was the presence of rhythmic sequences of synaptic potentials consisting of an EPSP closely followed by 2-6 IPSPs. These rhythmic sequences were superimposed on a small tonic hyperpolarization that lasted for the whole duration of the SWD and was still present at potentials close to -85 mV. The rhythmic IPSPs, on the other hand, had a reversal potential of -68 mV, and always appeared as depolarizing events when recording with KCl-filled electrodes at -55 mV. Low frequency electrical stimulation of the corresponding cortical area evoked in TC neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. The main feature of the intracellular activity recorded in cortical neurones during spontaneous SWDs was the presence of rhythmic depolarizations. Their frequency was similar to the one of SWDs in the EEG, and was not affected by DC injection. The amplitude of the rhythmic depolarizations, however, increased following steady hyperpolarization of the neurone by DC injection. An increase in the apparent input resistance of cortical neurones was observed during SWDs compared to the inter-SWDs periods. Low frequency electrical stimulation of the contralateral striatum evoked in cortical neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. Our data indicate that there are no rhythmic GABA(B) IPSPs and low threshold Ca2+ potentials in GAERS TC neurones during SWDs, but rhythmic sequences of EPSP/IPSPs superimposed on a tonic hyperpolarization that might represent a long lasting GABA(B) IPSP. Further experiments are required to clarify the nature of the voltage waveform and the increase in input resistance observed in cortical neurones during spontaneous SWDs in GAERS.

Animals↗
PubMed1999

In vivo induction of striatal long-term potentiation by low-frequency stimulation of the cerebral cortex.

Both long-term depression and long-term potentiation have been described at corticostriatal synapses. These long-lasting changes in synaptic strength were classically induced by high-frequency (100 Hz) electrical stimulations of cortical afferents. The purpose of the present study was to test the ability of corticostriatal connections to express use-dependent modifications after cortical stimulation applied at the frequency of synchronization of corticostriatal inputs observed in our in vivo preparation, i.e. the barbiturate-anesthetized rat. For this study we used an identified monosynaptic corticostriatal pathway, between the orofacial motor cortex and its target region in the striatum. Intracellular recording of striatal output neurons showed spontaneous large-amplitude oscillation-like depolarizations exhibiting a strong periodicity with a narrow frequency band at 5 Hz. Using the focal electroencephalogram of the cortical region projecting to the recorded cells, we found that membrane potential oscillations in striatal neurons were in phase with episodes of spontaneous cortical spindle waves. To determine directly the pattern of activity of corticostriatal neurons, we performed intracellular recordings of electrophysiologically identified corticostriatal neurons simultaneously with the corresponding surface electroencephalogram. We found that corticostriatal cells (n = 7) exhibited periods of spontaneous 5-Hz discharges in phase with the cortical spindle waves. Therefore, we have tested the effect of repetitive cortical stimulations at this low frequency (5 Hz, 500-1000 pulses) on the corticostriatal synaptic efficacy. In 62% of cases (eight of 13 neurons tested), this conditioning was able to produce long-term potentiation in the corticostriatal synaptic efficacy. The mean increase of excitatory postsynaptic potential amplitude ranged from 13.3% to 172% (mean = 67.3%, n = 8). These results provide additional support for physiological long-term potentiation at corticostriatal connections. Furthermore, this study demonstrates that corticostriatal long-term potentiation can be induced by synchronization at low frequency of cortical afferents. Our data support the concept that the striatal output neuron may operate as a coincidence detector of converging cortical information.

Animals↗
PubMed1998

Dendritic cells improve the generation of Epstein-Barr virus-specific cytotoxic T lymphocytes for the treatment of posttransplantation lymphoma.

BACKGROUND: The use of immunosuppressive therapies after solid organ transplantation has been shown to increase a patient's risk for Epstein-Barr virus (EBV)-associated lymphoma. A potential therapy for this disorder is the adoptive transfer of EBV-specific cytotoxic T lymphocytes (CTLs). We proposed that dendritic cells (DCs) could be loaded with EBV antigens and be used to improve the in vitro generation of EBV-specific CTLs. METHODS: Autologous EBV-transformed B-lymphoblastoid cell lines (BLCLs) were generated from normal donors, and CTLs were initiated by culturing peripheral blood mononuclear cells with DCs alone, disrupted BLCLs alone, intact, irradiated BLCLs alone, and DCs loaded with disrupted BLCLs. Lytic activities were determined with a 4-hour chromium-release assay against autologous BLCLs, and statistical calculations were performed by a Student t test assuming equal variance. RESULTS: The lytic activity of CTLs generated with DCs loaded with disrupted BLCLs reached 78% and was statistically significant (P < .01) at all effector/target ratios compared with CTLs generated with DCs alone, disrupted BLCLs alone, or intact BLCLs alone. Total numbers of CTLs were also greater than those of control groups for DCs loaded with disrupted BLCLs. CONCLUSIONS: DCs improved the in vitro generation of EBV-specific CTLs as evidenced by this group's significantly increased lytic activity over that of the control group. The improved lytic activity of DC-generated EBV-CTLs suggests that adoptive transfer of these cells could lead to a more effective immunotherapeutic response against posttransplantation EBV-associated lymphoma.

Antigens, Viral↗
PubMed1979

The structural organization of the pineal complex in the domestic goose.

The light and electron microscopic structure of the pineal complex of the domestic goose was studied. The complex is tubulofollicular but there is no direct connection between the constituent system of ducts and the third ventricle of the brain. Within the pineal, blood vessels accompanied by sympathetic nerve bundles are confined to the connective tissue. Other nerve fibers and occasional nerve cell bodies, however, do occur among the pineal cells. Threee basic pineal cell types were distinguished: (1) elongate epithelial cells which are arranged around follicles and ducts and resemble degenerate photoreceptor cells; (2) intramural supportive cells which are interspersed with elongate epithelial and intramural supportive cells; and (3) small supportive cells which lie between the bases of the elongate epithelial and intramural supportive cells. The follicular structure, vascularization, presence of secretory granules, and the nature of the elongate epithelial cells indicate that the pineal complex is primarily endocrine through a possible photoreceptive function cannot be ignored. Vesicles, 100-300 and 40-100 nm wide, were found with;n nerves and intramural supportive cells. The larger vesicles, present in pineals collected in the night, probably contain peptidic hormones. The smaller vesicles present in both day and night samples probably contain aminergic hormones.

Animals↗