Lidocaine for treatment of severe seizures in newborn infants. II. Blood concentrations of lidocaine and metabolites during intravenous infusion

The blood concentrations of lidocaine and its main active metabolites, methylethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in 24 newborn infants during anticonvulsive treatment with an iv infusion of lidocaine. After a bolus dose of 1.5-2.2 mg/kg and continuous infusion of lidocaine (4.7-6.3 mg/kg/h) there was accumulation of the drug and MEGX within 24 h. After termination of the iv infusion, both lidocaine and the metabolites were eliminated within 24-48 h. The anticonvulsive effectiveness--estimated by clinical observation and continuous amplitude integrated EEG monitoring (cerebral function monitor)--was immediate in 15 infants (nine term and six preterm). There was no correlation between blood concentrations of lidocaine and metabolites, and anticonvulsive effect (i.e. good, intermediate or no response). No differences in blood concentrations were found between full-term and preterm babies, or between infants with or without birth asphyxia. In combination with a fast withdrawal of the drug, few adverse reactions were seen with the dosages used, even though blood concentrations were high. Routine measurements of lidocaine concentrations during anticonvulsive treatment in neonates seem to be of little clinical value. For evaluation of the anticonvulsive effect and for early detection of seizure activity during lidocaine withdrawal, continuous EEG monitoring is preferable.     

Patterns of neuronal degeneration in the motor cortex of amyotrophic lateral sclerosis patients

Summary We examined patterns of neuronal degeneration in the motor cortex of amyotrophic lateral selerosis (ALS) patients using traditional cell stains and several histochemical markers including neurofilament, parvalbumin, NADPH-diaphorase, ubiquitin, Alz-50 and tau. Three grades of ALS (mild, moderate, severe) were defined based on the extent of Betz cell depletion. Non-phosphorylated neurofilament immunoreactive cortical pyramidal neurons and non-pyramidal parvalbumin local circuit neurons were significantly depleted in all grades of ALS. In contrast, NADPH-diaphorase neurons and Alz-50-positive neurons were quantitatively preserved despite reduced NADPH-diaphorase cellular staining and dendritic pruning. The density of ubiquitin-positive structures in the middle and deep layers of the motor cortex was increased in all cases. Axonal tau immunoreactivity was not altered. These histochemical results suggest that cortical degeneration in ALS is distinctive from other neurodegenerative diseases affecting cerebral cortex. Unlike Huntington's disease, both pyramidal and local cortical neurons are affected in ALS; unlike Alzheimer's disease, alteration of the neuronal cytoskeleton is not prominent. The unique pattern of neuronal degeneration found in ALS motor cortex is consistent with non-N-methyl-Dxxx-aspartate glutamate receptor-mediated cytotoxicity.Supported in part by a Muscular Dystrophy Association Research Development grant     

Inability of β-amyloid (25–35) to bind to central nervous system neurokinin 1 receptors

β-Amyloid (1–40) has recently been shown to exhibit both neurotoxic and neurotrophic properties. The putatively active moiety is β-(25–35), which has a structural homology to the human tachykinin substance P. Substance P, which preferentially binds to neurokinin 1 (NK1) receptors in the central nervous system (CNS), has been shown to block the neurotoxic effects of β-amyloid (1–40). These data suggest that effects of β-amyloid may be mediated by an NK1 receptor-mediated process. However, in the present study, we demonstrate that β-(25–35) is unable to competitively inhibit the binding of 0.15 nM ¹²⁵I-substance P from rat CNS NK1 receptors. Therefore, the mechanisms of action of β-amyloid neurotoxic effects are probably not to be mediated through a NK1 receptor-mediated process. © 1992 Wiley-Liss, Inc.     

Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra

Complex I dysfunction has been implicated in the pathogenesis of Parkinson's disease and in the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces a Parkinsonian syndrome in experimental animals and humans. Rotenone is an insecticide which is a specific inhibitor of complex I. We examined the pattern of central nervous system damage produced by i.v. systemic administration of rotenone in rats. Rotenone produced selective damage in the striatum and the globus pallidus, but the substantia nigra was spared. These results are consistent with prior reports suggesting that the selective vulnerability of the substantia nigra to MPTP involves both uptake by the dopamine transporter as well as complex I inhibition, and they show that rotenone produces a unique pattern of central nervous system damage. © 1997 Elsevier Science B.V. All rights reserved.     

Topical corticosteroids in dental practice

Topical corticosteroids represent an important therapeutic aid in the management of a range of oral mucosal disease conditions. Like all medications, their successful use depends upon an understanding of the disease process. This includes an appropriate diagnosis, a clear view of the desirable treatment outcomes and knowledge of whether treatment is aimed at management of a chronic disease or enhanced resolution of a short-term condition. This paper reviews the use of topical corticosteroids and their possible roles in the management of oral disease.     

NADPH diaphorase histochemistry of the human hypothalamus

The morphology and distribution of NADPH diaphorase reactive neurons was studied in the normal human hypothalamus. Reactive neurons were divided into three categories on the basis of perikaryal size. Small neurons (8–20 μm) were oval or fusiform, and pale staining. Intermediate neurons (20–30 μm) were fusiform, triangular or pyramidal with a wide range of staining intensity. Large neurons (> 30 μm) were triangular or pyramidal with moderate to dark staining. Reactive neurons were found in four major regions: medial preoptic, ventromedial, lateral, and perifornical. Scattered positive neurons were found in several other hypothalamic areas. Reactive fibers were present in the supraoptic decussation, medial forebrain bundle, and stria medullaris thalami.

The localization of NADPH diaphorase neurons in hypothalamic nuclei affected by Alzheimer's disease and other degenerative disorders suggests that further studies of this neuronal subset are warranted     

Tyrosine hydroxylase-like immunoreactivity is distributed in the matrix compartment of normal human and Huntington''s disease striatum

Tyrosine hydroxylase-like immunoreactivity (TH-lir) was examined in the adult human neostriatum and found to be heterogeneously distributed. Comparison of TH-lir with adjacent sections stained for acetylcholinesterase (AChE) activity showed that TH-lir is confined to the AChE-rich matrix compartment. TH-lir persists within the matrix zone, which is reduced in Huntington's disease (HD), suggesting that the nigrostriatal AChE projection may contribute to the persistent AChE patch-matrix pattern in HD. Despite marked striatal atrophy, the density of TH-immunoreactive fibers and terminals remained unchanged. This represents a loss of TH-positive extrinsic afferents in HD proportionate to striatal atrophy.     

Thy-1 in hippocampus: normal anatomy and neuritic growth in Alzheimer's disease.

Abnormal neuritic sprouting is a prominent feature of Alzheimer's disease (AD), and the Thy-1 glycoprotein has a role in neurite growth in culture. We therefore investigated the distribution of Thy-1 immunoreactivity in the hippocampus of normal elderly patients and of AD patients. Normally, Thy-1 immunoreactivity, which was more prominent in CA1 than elsewhere in the hippocampus, was located mainly in irregular patches on the perikarya of pyramidal cells, their dendrites and axons. In AD, Thy-1-immunoreactive neurons were reduced in number in CA1, and there was diffuse staining of neurofibrillary tangle-bearing pyramidal cells, but neurofibrillary tangles themselves were not immunoreactive. There was also staining of disorganized arrays of dystrophic neurites, some with spiny processes and bizarre filopodial endings. Some Thy-1-immunoreactive dystrophic neurites entered senile plaques. The data confirm that there is extensive growth of abnormal neurites in AD and suggest that Thy-1 is involved in this process.