An electroencephalographic study of 4-aminopyridine

The electroencephalographic (EEG) effects of 4-aminopyridine (4-AP) given intravenously in therapeutic doses were studied in four conscious human volunteers. 4-AP (0.2 mg/kg) caused an increase of the occipital alpha peak frequency of 0.4 to 1.0 Hz. In the dose range of 0.2 to 0.3 mg/kg there was neither evidence for epileptic activity in the EEG nor were any clinical side effects observed. This dose of 4-AP was also found to antagonize diazepam-induced sleep in four volunteers. In addition 4-AP (0.3 mg/kg) hastened the recovery by a factor of 4 in four patients having endoscopic procedures under diazepam-nitrous oxide anesthesia.     

Developmental features of exploration.

Developmentally analyzed the exploratory patterns of 112 4–12 yr olds. Ss were presented with groups of visual patterns, songs, and toys and asked about their preference for 1 item in each group. Analysis of the Ss' preferences for both visual and auditory stimuli revealed a significant increase in preference for complexity with age. Ss' preference for a unknown toy over a known toy was influenced by the novelty of the known toy. Ss were less likely to surrender a more novel known toy; this relation became stronger with age. Analysis of Ss' exploration of novel, concealed toys indicated that older Ss were more likely to systematically examine all the toys first before returning for a in-depth appraisal of particular toys of interest. The younger Ss were more likely to be captivated by a novel toy and not to finish examining the rest of the environment. There was some evidence of a qualitative jump in development between these 2 strategies. Younger Ss were also more likely to ask an adult questions as a means of acquiring information, and Ss of all ages asked most of their questions at the beginning of the exploratory task. (9 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A relative energy failure is associated with low-Mg2+ but not with 4-aminopyridine induced seizure-like events in entorhinal cortex

Interactions of the primary quinone acceptor QA of photosystem II (PS II) with surrounding amino acid residues were studied by analysis of FTIR difference spectra of QA upon its photoreduction (QA-/QA). Structural coupling with a His side chain was revealed by identifying the imidazole bands in the QA-/QA spectrum using the PS II core complexes from Synechocystis PCC 6803 in which both of the two imodazole nitrogens of His side chains were specifically labeled with 15N. Strong hydrogen bonding of the imidazole NH was shown by (i) the presence of several peaks at 2600-3000 cm-1, which arise from Fermi resonance of harmonics or combinations of imidazole ring modes with the hydrogen bonding NH stretching vibration, and (ii) the 1179 cm-1 band, which can be assigned to the mode including NH deformation, is at a frequency significantly higher than the corresponding 1151 cm-1 band of model compounds 4- and 5-methylimidazole in aqueous solution. Also, the presence of the bands specific to the Npi-protonated state at 1109/1102/1090 and 1359 cm-1 suggests that the QA-coupled His is protonated at the Npi site. These results are in good agreement with the model of QA interaction in which His215 (D2), which coordinates to the non-heme iron at Ntau, is hydrogen bonded to the QA carbonyl through the Npi-H bond. In contrast, no bands of Trp side chains were detected in the QA-/QA spectrum upon labeling of the indole ring of Trp residues with indole-d5. This result indicates that Trp254 (D2), which corresponds to Trp252 (M) of the bacterial reaction center that is located in van der Waals contact with QA, is not strongly coupled with QA in PS II. Probably, the predicted pi-pi interaction is not strong enough to influence the vibrations of the indole ring of Trp upon QA reduction, or Trp254 (D2) is located rather far from QA in PS II.     

N-methyl-D-aspartate antagonists, glutamate release inhibitors, 4-aminopyridine at neuromuscular transmission

GLP-1, an incretin hormone of the enteroinsular axis with insulinotropic and glucagonostatic activity, is secreted after nutrient ingestion. GLP-1 is mainly produced by intestinal L-cells in the lower gastrointestinal tract (GIT); simple carbohydrates are absorbed in the upper GIT and alpha-glucosidase inhibition leads to augmented and prolonged GLP-1 release in normal subjects. In a cross-over study, 100 mg acarbose or placebo was administered simultaneously with 100 g sucrose to 11 hyperglycaemic Type 2 diabetic patients poorly controlled with diet and sulphonylureas. Plasma levels of GLP-1, insulin, C-peptide, glugacon, GIP, glucose and H2-exhalation were measured over 6 h. Differences in the integrated responses over the observation period were evaluated by repeated measurement analysis of variance with fasting values used as covariates. With acarbose, sucrose reached the colon 60-90 min after ingestion as indicated by a significant increment in breath hydrogen exhalation (p = 0.005). After an early GLP-1 increment 15 min after sucrose under both conditions, GLP-1 release was prolonged in the acarbose group (p = 0.001; significant from 210 to 360 min.). Initially (0-150 min), glucose (p = 0.001), insulin (p = 0.001), and GIP (p < 0.001) were suppressed by acarbose, whereas later there were no significant differences. Glucagon levels were higher with acarbose in the last 3 h of the 6 h observation period (p = 0.02). We conclude that in hyperglycaemic Type 2 diabetic patients, ingestion of acarbose with a sucrose load leads to elevated and prolonged GLP-1 release.     

Developmental intrahepatic shunts of childhood: radiological features and management

The purpose of this study was to evaluate the role of radiological techniques in the diagnosis and management of developmental intrahepatic shunts. Hepatic vascular fistulae are recognised sequelae of liver trauma and intrahepatic tumours. However, there are rare developmental malformations which may present in childhood or later life and which may carry life-threatening complications. Retrospective analysis of clinical and radiological data was carried out in 24 patients. Anomalies evaluated were: (a) direct communication between hepatic artery and hepatic veins; (b) congenital hepatoportal arteriovenous malformations; and (c) congenital portocaval anastomosis with persistent flow through the ductus venosus. Although rare, the prompt recognition of these vascular anomalies allows early surgical or radiological intervention and reversal of the haemodynamic complications.     

Mechanism of block by 4-aminopyridine of the transient outward current in rat ventricular cardiomyocytes

Binocular information has been shown to be important for the programming and control of reaching and grasping. But even without binocular vision, people are still able to reach out and pick up objects accurately - albeit less efficiently. As part of a continuing investigation into the role that monocular cues play in visuomotor control, we examined whether or not subjects could use retinal motion information, derived from movements of the head, to help program and control reaching and grasping movements when binocular vision is denied. Subjects reached out in the dark to an illuminated sphere presented at eye-level, under both monocular and binocular viewing conditions with their head either free to move or restrained. When subjects viewed the display monocularly, they showed fewer on-line corrections when they were allowed to move their head. No such difference in performance was seen when subjects were allowed a full binocular view. This study, combined with previous work with neurological patients, confirms that the visuomotor system "prefers" to use binocular vision but, when this information is not available, can fall back on other monocular depth cues, such as information produced by motion of the object (and the scene) on the retina, to help program and control manual prehension.     

Developmental toxicity of 4-substituted amphetamines in mice

Until recently, therapy for most Nontuberculous Mycobacterial (NTM) disease, especially disease caused by Mycobacterium avium-complex (MAC), has been difficult and frustrating. The introduction of the newer macrolides (clarithromycin and azithromycin) has significantly added to the efficacy of regimens for both disseminated and pulmonary MAC disease. Clinical activity of these agents is lost when a MAC isolate develops in-vitro resistance that is facilitated by use of the macrolides as single agents. These valuable drugs should, therefore, never be used as single agents for the treatment of disseminated or pulmonary MAC disease. The newer macrolides also show promise for the treatment of other NTM infections such as those caused by M. abscessus, M. fortuitum, M. chelonae, M. xenopi, M. marinum, M. haemophilum, and M. genavense. Rifabutin, a derivative of rifamycin S, is an effective agent for prophylaxis against disseminated MAC and may have utility for treatment of pulmonary and disseminated MAC disease. Interactions between clarithromycin and rifamycin may alter efficacy of the macrolide and enhance toxicity of rifabutin. Although therapy of many NTM infections remains difficult with somewhat unpredictable results, the introduction of newer drugs, particularly the macrolides, has appreciably improved a previously dismal outlook for successful therapy.     

Effects of intracellular 4-aminopyridine and tetraethylammonium load on action potentials in the rabbit atrial myocardium

Investigated are rabbit atrial trabeculae (2-4 mm length, 150-800 micrometers diameter). When using a standard microelectrode technique, the action potentials after an intracellular 4-AP and TEA load are prolonged. Only the TEA load significantly diminishes the resting potential of the beating preparations. The typical configuration of the action potential following a period of rest (rapid initial repolarization, secondary depolarization and a late retarded repolarization) is not changed qualitatively. During a repetitive stimulation after a pacing pause the action potentials' restitution is accelerated at 4-AP. After 4-AP and TEA load the secondary depolarization of the first post rest action potential is more accentuated. By reconstructing the post rest action potentials a 4-AP sensitive current is determined. At constant drive this current shows a threshold potential at -40 and a reversal potential at -10 mV. The current is inward directed between -40 and -10 mV and is outward directed at more positive potentials than -10 mV. After a pacing pause the current-voltage relation is shifted to more negative potentials. The 4-AP sensitive current is modelled by consideration of a slow activated (during the action potential) and deactivated (during the pacing pause) conductivity. Processes of accumulation are discussed.     

Epinephrine proactive retardation of amygdala-kindled epileptogenesis.

Examined, in 3 experiments with 208 male Sprague-Dawley rats, the dose and temporal characteristics of epinephrine's retardant effects on the rate of kindling. In Exp I, the effects of lower doses of epinephrine (0.01, 0.1, or 1.0 mg/kg) on the development of kindled seizures was evaluated when the drug was administered 30 min or 24, 48, or 72 hrs before the 1st kindling trial. In Exp II, the effects of epinephrine (0.1 or 1.0 mg/kg) seizures were explored when the drug was administered to partially or fully kindled Ss. In Exp III, plasma catecholamine levels and cardiovascular responses were examined at 15 min and 1, 3, 5, and 24 hrs after epinephrine injection (0.1 or 1.0 mg/kg). Results indicate that epinephrine had dose- and time-dependent influences on amygdala kindling and acted primarily on the processes that established kindling and not on the kindled seizures per se. It is suggested that changes in plasma catecholamine levels, elevation in arterial blood pressure, and increase in heart rate do not appear to be sufficient explanations for epinephrine's long-term proactive attenuation of kindling. (17 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Focal epileptogenesis in a rat model of polymicrogyria

Polymicrogyria, a developmental cortical malformation associated with epilepsy, can be modeled in rats with a transcortical freeze lesion on the day of birth (P0) or P1. We have used field potential recordings to characterize the incidence, propagation patterns, and distribution of epileptiform activity in slices from rats with experimental microgyri. Interictal-like epileptiform activity was evoked in slices from 85% of freeze-lesioned rats aged P12-P118. These data show age-specific properties of epileptogenesis, including: a delay in onset, a decrease in the incidence of epileptiform activity in rats >P40 that was specific to those lesioned on P0 as opposed to P1, and a shift in the likely site of initiation to areas further from the microgyrus in mature animals. Several observations suggest that the area adjacent to the microgyrus, which appears histologically normal in Nissl stains, contains the necessary epileptogenic neuronal circuits: 1) in 78% of slices, epileptiform activity could be evoked only from a focal zone adjacent to the microgyrus (paramicrogyral zone) and not within the microgyrus proper; 2) epileptiform activity consistently originated from a particular site within this paramicrogyral zone, independent of the location of the stimulating electrode, suggesting that the generator is outside of the microgyrus; 3) evoked epileptiform activities in the paramicrogyral cortex were unaltered after separation of this zone from the microgyrus with a transcortical cut; and 4) the short-latency graded field potential evoked in the paramicrogyral zone contained an additional negativity not seen in control slices. The epileptiform activity was blocked reversibly by N-methyl--aspartate receptor antagonists in slices from mature as well as immature freeze-lesioned rats. These results suggest that aberrant synaptic connectivity develops in rat cortex surrounding the microgyrus and produces a focal epileptogenic zone whose capacity to generate epileptiform activities does not depend on connections with the malformation itself. We hypothesize that afferents, originating from cortical and extracortical sites, lose their targets in the region of the malformation and make appropriate laminar contacts in the cortex adjacent to the malformation, creating an overabundance of excitatory input to this cortical zone. Increased excitatory feedback onto specific cortical elements may be one factor involved in epileptogenesis in this model of a cortical malformation.     

Differential effects of 4-aminopyridine, serotonin, and phorbol esters on facilitation of sensorimotor connections in Aplysia

Serotonergic modulation of sensory neurons in Aplysia and their synaptic connections with follower cells has been used extensively as a model system with which to study mechanisms underlying neuronal plasticity. Serotonin (5-HT)-induced facilitation of sensorimotor connections is due to at least two processes: a process related to the broadening of presynaptic action potentials and a spike-duration-independent (SDI) process that may involve mobilization of transmitter. We have examined the relationship between spike broadening and synaptic facilitation of relatively nondepressed sensorimotor connections in the intact pleural-pedal ganglia. Previously, 5-HT-induced spike broadening in the sensory neuron was shown to be primarily due to the modulation of a voltage-dependent K+ current (Ik.v). Low concentrations (20-30 microM) of 4-aminopyridine (4-AP) were used to rather selectively block Ik.v. 4-AP increased spike duration in the sensory neuron and the excitatory postsynaptic potential (EPSP) in the motor neuron. The temporal development of 4-AP-induced spike broadening closely parallel that of synaptic facilitation. Thus spike broadening via the reduction of Ik.v can directly contribute to synaptic facilitation. The relationship between spike broadening induced by 5-HT (10 microM) and enhancement of the EPSP was also analyzed. We found that components of 5-HT-induced synaptic facilitation preceded the development of 5-HT-induced spike broadening. The comparison between the results of 4-AP and 5-HT revealed that the SDI processes made an important contribution to the rapid development of 5-HT-induced synaptic facilitation and that spike broadening made an important contribution to its maintenance. The SDI process and a slowly developing component of 5-HT-induced spike broadening are mediated, at least in part, by the activation of protein kinase C (PKC). Application of phorbol 12,13-diacetate (PDAc), an activator of PKC, partially mimicked the effects of 5-HT on spike duration and the EPSP. PDAc-induced enhancement of the EPSP preceded the slower development of PDAc-induced spike broadening. Like 5-HT, PDAc enhanced the EPSP via both spike broadening and the SDI processes. In addition, a 15-min exposure to PDAc occluded 5-HT-induced enhancement of the EPSP, suggesting that PKC and 5-HT engage similar or overlapping mechanisms. On the basis of these results and others, we propose a time-dependent hypothesis for the 5-HT-induced synaptic facilitation of nondepressed synapses, in which multiple second-messenger/protein kinase systems mediate the actions of 5-HT via both spike-duration-dependent and SDI processes.     

Radiation induced intracranial leiomyosarcoma: its histopathological features

This is a case of intracranial sarcoma which was recognized 23 years after irradiation therapy for pituitary adenoma. Four operations were performed because of recurrences with a short interval between each operation. Immunohistochemically, the tumour cells were stained for smooth muscle actin, human muscle actin and vimentin. It was verified as a leiomyosarcoma. This report is the first case of intracranial leiomyosarcoma associated with radiation therapy in pituitary adenoma.     

Developmental features of human striatal tissue transplanted in a rat model of Huntington''s disease

The actions of the novel calcium (Ca2+) channel antagonist mibefradil (Ro 40-5967), a selective T-type channel blocker in myocardium, were investigated in embryonic rat spinal motoneurones maintained in culture. Whole-cell currents were recorded with the patch-clamp technique. Motoneurones displayed transient, low-voltage-activated (LVA) and, more sustained, high-voltage-activated (HVA) Ca2+ currents. The LVA currents were small and preferentially blocked by amiloride and low doses of nickel. Most of the HVA Ca2+ current flowed through N-type Ca2+ channels, while L-, and P/Q-type channels represented a smaller fraction. Mibefradil caused a rapid and reversible dose-dependent block of inward Ca2+ channel currents. Inhibition was nearly complete at 10 microM, suggesting mibefradil blockade of all subclasses of Ca2+ channels. The IC50 was approximately 1.4 microM on currents measured at 0 mV, from a holding potential of -90 mV. Inhibition of LVA Ca2+ current occurred over the same contraction range. Slow tail currents induced by the dihydropyridine agonist Bay K 8644 were also blocked by mibefradil, although with a slightly lower potency (IC50 = 3.4 microM). These broad inhibitory effects of mibefradil on Ca2+ influx were also supported by the strong inhibition of depolarization-induced intracellular calcium transients, measured from Indo-1 loaded motoneurones imaged with confocal microscopy. We conclude that mibefradil has potent blocking effects on Ca2+ channels in mammalian motoneurones. We hypothesize that therapeutic and pharmacological effects of mibefradil may involve actions on Ca2+ channels other than type T.     

Developmental changes in enzyme activities and in structural features of rat masticatory muscle mitochondria

The functional ability of a muscle is closely related to the activities of the mitochondria, which are energy-producing organelles in muscle cells. The development of the mammalian masticatory muscle progresses dramatically when feeding behavior changes from suckling to mastication, but it is unclear how the energy-producing systems of the mitochondria change. In this paper, the development of rat masticatory muscle mitochondria was investigated in terms of enzyme activities of the mitochondrial respiratory chain and the structural and numerical development of mitochondria, especially regarding the change in feeding behavior from suckling to mastication. Using isolated mitochondria from the masticatory muscle, we measured succinate dehydrogenase, NADH dehydrogenase, succinate-O2 oxidoreductase, and NADH-O2 oxidoreductase. These were found to be increased in the 15-day postnatal rat compared with the 0- to 10-day postnatal rat. The structural development of mitochondria was gradual in the 0- to 15-day postnatal rat. However, a notable increase was found in the cross-sectional area of mitochondria between 10 and 15 days postnatally. The number of mitochondria per muscle fiber was apparently constant during the same period. We demonstrated that the change in feeding behavior was well-correlated with an increase in mitochondrial enzyme activity, also supported by the early structural development of mitochondria.     

Differential effects of low and high concentrations of 4-aminopyridine on axonal conduction in normal and injured spinal cord

Laminins, the main components of basement membranes, are heterotrimers consisting of alpha, beta, and gamma polypeptide chains linked together by disulfide bonds. Laminins-1 and -2 are both composed of beta1 and gamma1 chains and differ from each other on their alpha chain, which is alpha1 and alpha2 for laminin-1 and -2, respectively. The present study shows that whereas laminins-1 and -2 are synthesized in the mouse developing lung and in epithelial-mesenchymal cocultures derived from it, epithelial and mesenchymal monocultures lose their ability to synthesize the laminin alpha1 chain. Synthesis of laminin alpha1 chain however returns upon re-establishment of epithelial-mesenchymal contact. Cell-cell contact is critical, since laminin alpha1 chain is not detected in monocultures exposed to coculture-conditioned medium or in epithelial-mesenchymal cocultures in which heterotypic cell-cell contact is prevented by an interposing filter. Immunohistochemical studies on cocultures treated with brefeldin A, an inhibitor of protein secretion, indicated both epithelial and mesenchymal cells synthesize laminin alpha1 chain upon heterotypic cell- cell contact. In a set of functional studies, embryonic lung explants were cultured in the presence of monoclonal antibodies to laminin alpha1, alpha2, and beta/gamma chains. Lung explants exposed to monoclonal antibodies to laminin alpha1 chain exhibited alterations in peribronchial cell shape and decreased smooth muscle development, as indicated by low levels of smooth muscle alpha actin and desmin. Taken together, our studies suggest that laminin alpha1 chain synthesis is regulated by epithelial-mesenchymal interaction and may play a role in airway smooth muscle development.     

The neurobiological bases of epileptogenesis in the developing brain

The basics of neurophysiological, neurochemical and molecular mechanisms of epileptogenesis in early ontogeny are discussed. The role of developmental neuropathology, synaptogenesis; the role of glutamatergic and GABA-ergic transmitter systems are summarized. The candidates of genes in the childhood epilepsies, developmental changes in the expression of genes of voltage-gated ionic channels and receptor genes are reviewed.     

Developmental and tissue-specific expression of human CD4 in transgenic rabbits

A major obstacle to understanding AIDS is the lack of a suitable small animal model for studying HIV-1 infection and the subsequent development of AIDS, and for testing diagnostic, therapeutic, and preventive modalities. Our goal is to produce a rabbit model for the study of AIDS. Here we report on the generation of transgenic rabbits that express the human CD4 (hCD4) gene. The transgene, which contains the coding region for hCD4 and approximately 23 kb of sequence upstream of the translation start site, was used previously to direct hcD4 expression on the surface of CD4+ T cells of transgenic mice (Gillespie et al., 1993: Mol Cell Biol 13:2952-2958). The hCD4 transgene was detected in five males and two females derived from the microinjection in five males and two females derived from the microinjection of 271 rabbit embryos. Both hCD4 RNA and protein were expressed in peripheral blood lymphocytes (PBLs) from all five males but neither of the females. Human CD4 was expressed on PBLs from F1 offspring of all founder males. T-cell subset analysis revealed that hCD4 expression was restricted to rabbit CD4 (rCD4) expressing lymphocytes; mature rCD4- rCD8+ lymphocytes did not express hCD4. In preliminary studies, PBLs from hCD4 transgenic rabbits produced greater amounts of HIV-1 p24 core protein following HIV-1 infection in vitro than HIV-1 p24 antigen in nontransgenic rabbit infected cultures. These results extend to rabbits our previous observation that this transgene contains the sequence elements required for high-level expression in the appropriate cells of transgenic mice. Furthermore, these and previous studies demonstrating that expression of hCD4 protein enhances HIV-1 infection of rabbit T cells in vitro, coupled with reports that normal, nontransgenic rabbits are susceptible to HIV-1 infection, suggests that the hCD4 transgenic rabbits described herein will have an increased susceptibility to HIV-1 infection. In vivo HIV-1 infection studies with these rabbits are under way.     

Suppression of kindling epileptogenesis in rats by intrahippocampal cholinergic grafts

The objective of our study was to investigate the effects of ultrasonic energy on tissues, using a porcine model, performed under various instrumental and procedural parameters. Domestic pigs were anesthetized and prepared for surgery. An incision was made on the side of the hip randomly assigned to the right or left side. Tumescence solution was infiltrated via a blunt tip, small diameter cannula, followed by performance of standard liposuction. On the contralateral side, a similar incision was made. For ultrasonic liposuction experiments without the sheath, a percutaneous introducer was inserted into the incision, which was protected at the entry site from contact with the cannula. Tumescence solution was infiltrated via a blunt tip, small diameter cannula, and then the site was treated with ultrasonic energy at maximum output from the machine with liposuction concurrent through the hollow cannula. The experiments with the sheath did not require a pretreatment with tumescence solution but consisted of tumescence solution pumped through the sheath at a low infusion rate, with concurrent treatment utilizing ultrasonically assisted liposuction through the central lumen of the cannula. In all cases, the lipoaspirate was preserved for biochemical analysis. After treatment, the pigs were euthanized, and samples for histopathology were taken. The pigs were then perfused with a radio-opaque solution through the left ventricle following preperfusion with saline. The groups were ultrasound-assisted liposuction with sheath (n = 3), ultrasound-assisted without sheath (n = 4), and tumescence alone (n = 1), with standard liposuction performed on the contralateral side for all ultrasound-assisted liposuction animals. The lipoaspirates from the ultrasonically assisted liposuction with the sheath showed significantly less blood loss (measured as hemoglobin in the aspirate) than standard liposuction (p = 0.012) at comparable levels of fat (measured as triglycerides in the aspirate). The lipoaspirates from ultrasound-assisted liposuction without the sheath showed blood loss comparable to that experienced with standard liposuction. The ratio of hemoglobin to triglyceride was lowest in the ultrasound-assisted group with (p = 0.01) and without (p = 0.06) the sheath when compared to traditional liposuction. In both of these treated groups, the radiograms of the perfused areas showed significantly less vascular disruption when compared with suction-assisted liposuction. Histopathologic examination of specimens taken from various treated areas showed substantial tissue damage comparable in ultrasound- and suction-assisted liposuction treated groups. This preliminary experimental study showed that ultrasound-assisted lipoplasty is comparable to traditional suction-assisted lipoplasty. Treatment with ultrasound provided more significant hemoglobin/triglyceride ratios, indicative of more lipid aspirated per hemoglobin lost, and better preservation of vascular tissues as demonstrated by our perfusion studies. Treatment with the sheath showed a significantly lower hemoglobin release with a diminished volume infused into the subcutaneous space during the procedure.     

Magnetic resonance imaging of epilepsy in multiple sclerosis: a case control study. Implications for treatment trials with 4-aminopyridine

A statistically significant (p = 0.049) increase in methemoglobin (MetHb), which did not exceed normal values, was noted 8 h after application of 1 g of EMLA (Eutectic Mixture of Local Anesthetics) to the foreskin of 10 normal newborns to reduce pain associated with circumcision. The highest MetHb concentration observed was 3 g/l (toxic > 50 g/l). No infant showed clinical signs of methemoglobinemia. We conclude that EMLA is safe to use as a local anesthetic in term neonates.     

Opposite modulation of 4-aminopyridine and hypoxic hyperexcitability by A1 and A2 adenosine receptor ligands in rat hippocampal slices

A randomly selected, age-stratified sample of subjects 50 years of age and older, living in the Salford Health District area of Greater Manchester was drawn from the age-sex register of a four-doctor group practice and invited by post to enter a study of ptosis. Of 851 subjects approached, 499 (59%) replied. Of these, 99 refused to participate. The remaining 400 were visited at home and underwent a standardized protocol of ophthalmic history, and examination including a photograph of the eyes in the primary position. Forty-six (11.5%) of the subjects had ptosis and its prevalence increased with age. Ptosis was bilateral in 18 (39%) and unilateral in 28 (61%). In all but four cases, the ptosis was acquired. The cause was evident in 23 (50%), with 11 cases being due to mechanical ptosis and 12 to aponeurotic disinsertion secondary to a known pathology. A further 22 cases had primary aponeurotic disinsertion and there was one case of probable myasthenia gravis. The prevalence of pupillary diameter of 1 mm or less increased significantly with age.