Early progressive encephalopathy in boys and MECP2 mutations.

MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

Interactions of lidocaine and calcium in blocking the compound action potential of frog sciatic nerve.

The exact role of calcium in nerve conduction in neurons that have been blocked by local anesthetics remains controversial. Recently, attention has been drawn to the importance of examining both frequency-dependent and nonfrequency-dependent conduction block, since it is felt that frequency-dependent block provides a model that more closely approximates the normal physiologic state. The present study was designed to examine the effects of calcium on both the nonfrequency-dependent and frequency-dependent components of lidocaine nerve block. Desheathed, whole sciatic nerves from frogs were placed in a sucrose gap chamber and stimulated by trains of 20 impulses at frequencies from 3 to 90 Hz at supramaximal intensity for activation of the compound action potential. After control studies, the nerve was bathed by a frog Ringer's solution containing calcium concentrations, which increased from 0.0 mM to the physiologic value of 2.0 mM with or without 0.5 mM lidocaine. Compound action potentials were measured, and both frequency-dependent block and nonfrequency-dependent block were compared in each solution. Low calcium concentrations significantly enhanced both nonfrequency- and frequency-dependent lidocaine block. The effect of low concentrations of calcium was greater at higher frequencies of stimulation.

Tetraethylammonium derivatives: ultralong-acting local anesthetics?

Derivatives of tetraethylammonium ion (TEA+) were synthesized in which one ethyl group was replaced by a C6, C8, C10, C12, C14, or C16 side chain. These TEA+ derivatives were tested for duration of sensory block of the rat infraorbital (trigeminal) nerve. The duration of sensory anesthesia increased exponentially from 1.2 hours to 388 hours as chain length increased from C2-C12, while C12, C14, and C16 all produced a similar reversible block of 17--20 days. The block duration of C12 was correlated with C12 bound to the infraorbital nerve; C12 not bound by the nerve was quantitatively excreted by the kidneys. These data, along with the lack of observable microscopic toxicity, suggests that TEA+ derivatives may be a useful new class of ultralong-acting local anesthetics.

The mechanism of action of local anesthesia by tetraethylammonium derivatives.

Tetraethylammonium (TEA+) derivatives in which one of the ethyl groups is replaced by a longer chain alkane (C4-C16) were tested for their ability to block the compound action potential (CAP) of frog sciatic nerve. A parabolic relation between chain length and 100 per cent blocking dose was found, suggesting an optimal size of C12 for the inhibitory receptor. Two types of inhibition were observed. Type 1 was an inhibition of the CAP at all frequencies when the nerve was perfused with the TEA+ derivative. Interaction with tetrodotoxin suggests this is a Na+ channel effect. Type 2 was an irreversible (still present after nerve wash) frequency-dependent inhibition that is distinct from and synergistic with Na+ channel blocking local anesthetics. From the kinetics of inhibition onset and transport studies, it is suggested that the ultralong action of the TEA+ derivatives is mediated by binding to a receptor at the internal part of K+ channels.

Intercostal nerve block: a roentgenographic anatomic study of technique and absorption in humans.

Roentgenograms of iothalamate meglumine 60% (Conray) injected bilaterally into the intercostal grooves of the ninth or tenth ribs in 30 surgical patients showed extensive spread of the contrast central and peripherally from the site of injection within 30 seconds, with almost complete absorption within 10 minutes 30 seconds. The spread was visualized in two patients for diagnosis using CT (computed tomography) following injection of iothalamate. It was also confirmed by injecting liquid latex into two corpses prior to autopsy. These findings help to explain why the peak plasma level occurs more rapidly and is higher following intercostal nerve block than from other regional nerve blocks when comparable doses are injected. Also, the study revealed that the optimal site for blocking an intercostal nerve is at the angle of the rib and that the optimal needle is one with a short bevel.

The clinical character of local anesthetics: a function of frequency-dependent conduction block.

It is clinically recognized fact that some local anesthetics have a proclivity for inhibition of motor nerves, while others preferentially affect sensory and sympathetic fibers. On the basis that sensory fibers have a frequency threshold for transmission of nociceptive stimuli and that somatic motor fibers have no such frequency threshold, we hypothesized that this variation may be due to differences in the effect of local anesthetics on axonal refractory period. Frog sciatic nerves were partially blocked with lidocaine, bupivacaine, tetracaine and etidocaine, and then stimulated in trains of 17 pulses, at frequencies between 3 and 100 Hz. The height and area of the last action potential in a train were measured. At a comparable level of partial block (50% at 100 Hz), tetracaine and etidocaine showed only a 10% difference between 3 and 100 Hz, while with bupivacaine and lidocaine there was a 30% drop between these two frequencies. This excellent correlation between the laboratory and clinical phenomenon supports our hypothesis. Local anesthetics which have a minimal effect on the refractory period yield enhanced motor block; whereas local anesthetics with a large effect on the refractory period are relatively more potent blockers of sensory and sympathetic transmission.

Neonatal meningitis and circumcision.

This paper presents four cases of fulminating neonatal sepsis with meningitis. In each infant, there was evidence of an infected circumcision wound. Two infants had Escherichia coli and two had Group B haemolytic streptococcus cultured from the cerebrospinal fluid. One infant died. The risk of introducing infection through iatrogenic portals of entry is a definite problem in the neonate. Circumcision is an unnecessary routine procedure, which puts the infant at risk.

Differential B and C fibre block by an amide- and an ester-linked local anaesthetic.

The relative sensitivity of sympathetic preganglionic and postganglionic axons, B and C fibres, respectively, to two structurally dissimilar local anaesthetics was examined. The concentration of amethocaine (ester-linked tertiary amine) or prilocaine (amide-linked secondary amine) required to reduce the B fibre compound action potential by 50% was one-third of the concentration required to depress the C fibre potential to a similar extent. Both local anaesthetic agents also showed the action potential propagation through B fibres more than through C fibres. Similar results have been reported previously for lignocaine (amide-linked tertiary amine).