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Biomedical subjects

E H Lambert

Publications and source records attributed to E H Lambert.

At least 73 records · Page 4Linked to original sources
PubMed1978

Structure-function correlations in myasthenia gravis and a new myasthenic syndrome.

The physiologic hallmark of MG is the small amplitude of the mepp. This can be correlated with a deficiency of postsynaptic AChR. The AChR deficiency is caused by antiAChR antibodies. Antibody dependent, complement mediated lysis of the postsynaptic membrane contributes significantly to the AChR deficiency. The abundance of immune complexes localized at the end-plate correlates with the amount of AChR remaining at the end-plate and with the mepp amplitude. The physiologic hallmarks of the new myasthenic syndrome are a small quantum content of the end-plate potential due to a decreased store of immediately releasable quanta, repetitive response of the muscle to a single nerve stimulus and refractoriness to anticholinesterase drugs. The findings are explained by a marked decrease of the size of the nerve terminal and by the total absence of AChE from the end-plate.

Adolescent↗
PubMed1978

Sensory nerve conduction velocity in children using cerebral evoked potentials.

Sensory nerve conduction velocity was measured in 16 healthy volunteers from 3 to 16 years of age by using evoked cortical potentials. Using the latencies to the peaks of the 2nd and 3rd components (N1 and P2) of the average evoked response, conduction velocities for the wrist-to-elbow segment of the median nerve were found to have a range of 58 to 74 meters/second (m/s). Mean values using N1 and P2 were not significantly different. Conduction velocities in the same children obtained by stimulation of the median nerve at the elbow and wrist while recording the digital nerve action potential from the index finger had a range of 58 to 70 m/s. Mean values determined using cortical and digital potentials were not significantly different. In individual subjects, values obtained with the two techniques differed by 0 to 9 m/s using the N1 peak and 0 to 11 m/s using the P2 peak of the of the cortical potential. Reliable conduction velocity measurements for sensory nerves can be obtained in children using evoked cortical potentials with relatively simple methods. This technique has been successful when conventional methods did not detect peripheral sensory responses.

Charcot-Marie-Tooth Disease↗
PubMed1977

A new myasthenic syndrome with end-plate acetylcholinesterase deficiency, small nerve terminals, and reduced acetylcholine release.

A new myasthenic syndrome is described in a patient whose symptoms began soon after birth and included generalized weakness increased by exertion, easy fatigability, hyporeflexia, and refractoriness to anticholinesterase drugs. Electromyography showed a decremental response at all frequencies of stimulation and a repetitive response to single nerve stimulation. Miniature end-plate potentials (mepps) were of normal amplitude but of decreased frequency. The mepp duration and half-decay time were prolonged, and prostigmine was without any addtitional effect. The quantum content of the end-plate potential was decreased due to a reduced store of quanta immediately available for release, but the probability of release was normal. Quantitative electron microscopy demonstrated a 3-fold to 4-fold decrease of nerve terminal size and reduced postsynaptic membrane density. The postsynaptic folds showed focal degeneration, and many were distended by labyrinthine membranous networks that communicated with the synaptic space. Degenerating nuclei were found in the junctional sarcoplasm. The ultrastructural localization of the acetylcholine receptor protein was normal. Acetylcholinesterase (AChE) was absent from the motor end-plates by histochemical and electron cytochemical criteria. Biochemical studies indicated total absence of the end-plate-specific 16 S species of AChE and marked decrease in total muscle AChE. A congenital defect in the molecular assembly of AChE or in its attachment to the postsynaptic membrane might represent the basic abnormality and condition the morphological and physiological alterations.

Acetylcholine↗
PubMed1977

Computerized image recognition for morphometry of nerve attribute of shape of sampled transverse sections of myelinated fibers which best estimates their average diameter.

A computerized image recognition method was used to measure various attributes of shape of cross-sections of myelinated nerve fibers. Measurements were made at intervals over 1/2 internode of each fiber on 20 fibers from each of 4 sural nerves from rats. Diameters were computed in 6 different ways from the computer measurements and compared for bias, precision, and accuracy between sections and to the diameter of an idealized cylinder reconstructed for each fiber from multiple actual cross sections. The diameter computed from cross-sectional areas of transversely sectioned myelinated fibers, converted into a circle, showed the highest precision, greatest accuracy and least bias. Fibers were classified by shape and the frequency was determined in defined regions (I1 = paranodal, I3= nuclear and I2=region between I1 and I3) of the 1/2 internode. A crenated shape is highly characteristic of the I1 region. The boomerang shape was found most frequently in I3 whereas the circular shape was found most frequently in I2. Epileptical and boomerang shapes of myelinated fibers within fascicles which have been orientated carefully to obtain transverse sections, are not due to obliquity of section. Therefore, using the minor axis to determine the diameter of such profiles, as we had done previously in our laboratory, is in error. We conclude from these studies, that in carefully orientated transverse sections of nerve trucks, the diameter calculated from measurement of area converted to a circular shape is the best among the various estimates of myelinated fiber diameter and is the most suitable one for use in computerized image recognition systems for nerve morphometry. It seems reasonable to extrapolate this general conclusion to myelinated fibers of man.

Animals↗
PubMed1977

Ultrastructural localization of the acetylcholine receptor in myasthenia gravis and in its experimental autoimmune model.

Peroxidase-conjugated alpha-bungarotoxin (P-BGT) was used for the ultrastructural localization of the acetylcholine receptor in end-plates in external intercostal muscles of four patients with myasthenia gravis, in forelimb digit extensor muscles of rats with advanced chronic experimental autoimmune myasthenia gravis, and in suitable human and rat controls. In control end-plates, the previously reported localization of acetylcholine receptor on the terminal expansions of the postsynaptic folds and, in traces, on the presynaptic membrane was confirmed. By contrast, in myasthenia gravis some postsynaptic regions bound no P-BGT; in other regions, the folds displayed only faint traces of the reaction product, or only some segments of the postsynaptic membrane showed the reaction product; finally, in some regions there was no apparent decrease in reaction product. In general, those postsynaptic regions showing the greatest decrease in P-BGT binding were also the simplest or showed the most degenerative changes, and the presynaptic staining was decreased in proportion to the decrease in the adjacent postsynaptic P-BGT binding. In the experimental animals, the abnormalities in the amount and distribution of the acetylcholine receptor were essentially like those in the more severely affected patients. Morphometric estimates of the postsynaptic acetylcholine receptor surface correlated well with the patients' clinical status and linearly with the miniature end-plate potential amplitude.

Action Potentials↗
PubMed1977

Duchenne dystrophy: ultrastructural localization of the acetylcholine receptor and intracellular microelectrode studies of neuromuscular transmission.

Despite focal degeneration and simplification of the postsynaptic region in Duchenne dystrophy, the postsynaptic acetylcholine receptor (AChR) is preserved. This is in contrast to myasthenia gravis where similar postsynaptic alterations are invariably associated with a marked decrease in AChR. There is no extrajunctional spread of AChR in Duchenne dystrophy. The amplitude and frequency of miniature end-plate potentials and the number of transmitter quanta released by nerve impulse are normal but the resting membrane potential is lower than normal. The findings indicate that the release and the postsynaptic responsiveness to acetylcholine are intact in Duchenne dystrophy.

Acetylcholine↗
PubMed1977

Lead neuropathy. 1) Morphometry, nerve conduction, and choline acetyltransferase transport: new finding of endoneurial edema associated with segmental demyelination.

Morphometric and pathologic studies along the length of the peripheral nervous system were obtained in groups of rats fed 4% lead carbonate for 3 and 6 months and in match-fed controls. The number and diameter histograms of L6 cytons of spinal ganglia and of myelinated fibers of proximal and distal portions of peroneal and sural nerve were not significantly different from the control groups. On the other hand, segmental demyelination occurred approximately as frequently in proximal as in distal parts of nerves. At 3 months approximately 1/3 of teased myelinated fibers showed changes of segmental demyelination (Condition C), or of remyelination after segmental demyelination (Condition F) or of both segmental demyelination and of remyelination (Condition D), while at 6 months more than 4/5ths of fibers showed these changes. As expected, regression lines of axonal area on number of lamellae of myelin, were less steep in nerves of rats fed on lead for 6 months as compared to controls. Axonal transport of choline acetyltransferase in lead neuropathy did not differ from that in control rats. As expected from the studies of others, conduction velocity of myelinated fibers of caudal nerve were low. A new finding was the often quite striking increase of transverse fascicular area of peripheral nerves. This was due to edema which appeared to develop at about the time of onset os segmental demyelination. Although the edema may be an epiphenomenon, it could be an important observation bearing on the development of lead neuropathy. It would be important to know next whether or not the blood nerve barrier is altered in lead neuropathy.

Animals↗
PubMed1977

Immune complexes (IgG and C3) at the motor end-plate in myasthenia gravis: ultrastructural and light microscopic localization and electrophysiologic correlations.

Although there is strong evidence that myasthenia gravis (MG) is caused by an autoimmune reaction to the nicotinic postsynaptic acetylcholine receptor (AChR) protein, immune complexes have never been directly demonstrated at the end-plate by immunocyto-chemistry or immunoelectron microscopy. Staphylococcal protein A (which binds to the Fc region of human IgG subclasses 1, 2, and 4) and rabbit anti-human C3 conjugated with peroxidase were used for the ultrastructural (5 patients) and light microscopic (12 patients) localization of IgG and C3, respectively, at MG end-plates. Both IgG and C3 were localized on segments of the postsynaptic membrance and fragments of degenerating junctional folds in the synaptic space. In nonmyasthenic control patients no immune complexes were evident at the end-plate. As judged by morphometric analysis of electron micrographs, the immune complexes were more abundant in the less severely affected MG patients than in the more severely affected ones. A linear correlation was demonstrated between the length of the postsynaptic membrance binding immune complexes and the amplitude of the miniature end-plate potential. The less intense reaction for immune complexes in the more severely affected MG patients can be attributed to the smaller quantity of AChR remaining at their end-plates. The findings provide unambiguous evidence for a destructive auto-immune reaction involving the postsynaptic membrance in MG. Immunopharmacologic blockade of AChR and IgG-induced modulation of AChR may also contribute to the AChR deficiency at the MG end-plates.

Adult↗
PubMed1976

Pathological mechanisms in experimental autoimmune myasthenia gravis. II. Passive transfer of experimental autoimmune myasthenia gravis in rats with anti-acetylcholine recepotr antibodies.

Passive transfer of experimental autoimmune myasthenia gravis (EAMG) was achieved using the gamma globulin fraction and purified IgG from sera of rats immunized with Electrophus electricus (eel) acetylcholine receptor (AChR). This demonstrates the critical role of anti-AChR antibodies in impairing neuromuscular transmission in EAMG. Passive transfer of anti-AChR antibodies from rats with chronic EAMG induced signs of the acute phase of EAMG in normal recipient rats, including invasion of the motor end-plate region by mononuclear inflammatory cells. Clinical, eletrophysiological, histological, and biochemical signs of acute EAMG were observed by 24 h after antibody transfer. Recipient rats developed profound weakness and fatigability, and the posture characteristic of EAMG. Striking weight loss was attributable to dehydration. Recipient rats showed large decreases in amplitude of muscle responses to motor nerve stimulation, and repetitive nerve stimulation induced characteristic decrementing responses. End-plate potentials were not detectable in many muscle fibers, and the amplitudes of miniature end-plate potentials were reduced in the others. Passively transferred EAMG more severely affected the forearm muscles than diaphragm muscles, though neuromuscular transmission was impaired and curare sensitivity was increased in both muscles. Some AChR extracted from the muscles of rats with passively transferred EAMG was found to be complexed with antibody, and the total yield of AChR per rat was decreased. The quantitative decrease in AChR approximately paralleled in time the course of clinical and electrophysiological signs. The amount of AChR increased to normal levels and beyond at the time neuromuscular transmission was improving. The excess of AChR extractable from muscle as the serum antibody level decreased probably represented extrajunctional receptors formed in response to functional denervation caused by phagocytosis of the postsynaptic membrane by macrophages. The amount of antibody required to passively transfer EAMG was less than required to bind all AChR molecules in a rat's musculature. The effectiveness of samll amounts of antibody was probably amplified by the activation of complement and by the destruction of large areas of postsynaptic membrane by phagocytic cells. A self-sustaining autoimmune response to AChR was not provoked in animals with passively transferred EAMG.

Animals↗
PubMed1976

End-plate potentials in experimental autoimmune myasthenia gravis in rats.

Rats inoculated once with nicotinic acetylcholine receptor and adjuvants had two episodes of weakness, the first being acute and transient, starting on day 8, and remitting in a few days, the second, chronic, progressive, and appearing after day 20. In the acute phase, the compound action potential and twitch evoked in weak forelimb muscles by maximal nerve stimulus were greatly reduced. Nerve action potentials were normal, however, and the muscle responded to direct electrical stimulation. Using intracellular microelectrodes, miniature end-plate potentials were difficult to find and often were low in amplitude. Many fibers were functionally denervated; no action potential or end-plate potential was evoked by nerve stimulus, although the muscle fiber responded to direct stimulation. In fibers with EEPs the number of acetylcholine quanta released by nerve impulse, the store of quanta readily available for release and the mobilization rate were low. The diaphragm was similarly, but less severely affected. Recovery from the acute phase occurred in a few days with restoration of the response of forelimb muscle to nerve stimulus, even though MEPP amplitude remained low. In the chronic phase, in both forelimb muscle and diaphragm, MEPP were more easily found, but in all rats MEPP amplitude was below normal whether or not there was weakness or a decrement in the EMG. The number of quanta released by nerve stimulus, the store, and the mobilization rate of quanta were normal in all animals. The titer of antibodies ot syngeneic acetylcholine receptor was elevated in all chronic phase animals. The chronic phase is like myasthenia gravis, but rats with MEPP amplitudes as low as those in patients with MG frequently were not weak, because the number of ACh quanta released per nerve impulse is greater in the rat than in man.

Acetylcholine↗
PubMed1976

Alternate-day prednisone: preliminary report of a double-blind controlled study.

Thirteen patients with moderately severe myasthenia gravis participated in a double-blind study using either 100 mg of prednisone or an equivalen numbder of placebo tablets on alternate days. Anticholinesterase therapy was continued on a demand basis. At the end of 6 months the code was broken. Seven patients were on placebo and three of these had improved to such a degree that steroid therapy was not indicated. Four of these patients ultimately were started on prednisone and improved. Of the six patients on prednisone, three showed no improvement and three were improved. At the end of 2 years, the seven patients still taking prednisone were on maintenance dosage of this drug. Three of this group had experienced relapses when the dosage was cut to 15 to 25 mg on alternate days, and they again improved when the prednisone dosage was increased. No statistical evaluation is possible because of the small number of patients. It can be stated that seven patients improved with steroid therapy. Conversely, not all patients treated with alternate-day prednisone improved. Finally, any evaluation of treatment of myasthenia gravis must take into consideration the potential for spontaneous improvement, as demonstrated by three of the patients treated with placebo.

Adrenocorticotropic Hormone↗
PubMed1976

Pain in peripheral neuropathy related to rate and kind of fiber degeneration.

In a series of 72 patients with disease of peripheral neurons, neuropathic painfulness of the foot was found to be related to the rate and kind of nerve fiber degeneration. Patients with acute breakdown of myelinated fibers (either by wallerian or axonal degeneration) tend to have pain more often and to a greater degree than do patients with more chronic forms of nerve fiber degeneration. Neuropathic painfulness was not found to be related simply to the ratio of remaining large and small fibers after nerve fiber degeneration. These studies do not fit the expectation of the proponents of the gate theory of pain.

Action Potentials↗
PubMed1975

Uremic neuropathy. III. Controlled study of restricted protein and fluid diet and infrequent hemodialysis versus conventional hemodialysis treatment.

The effect of a treatment schedule of restricted protein and fluid intake and of infrequent hemodialysis (schedule 1) as compared to a conventional hemodialysis treatment schedule (schedule 2) on the presence and severity of peripheral neuropathy has been studied in a small group of patients using a crossover design. Using the neurologic evaluation and quantitative assessment of cutaneous sensation and of nerve conduction as indices of peripheral nerve function, we have not demonstrated any worsening of peripheral nerve function from markedly curtailing the frequency of hemodialysis and modifying the diet. Because of the small size of the study, the preponderance of patients receiving the test treatment schedule first, and the possibility that nerve function slowly worsens with time, it is not possible to say with certainty that the test or the control treatment schedule might adversely affect peripheral nerve function. If such an effect is present it would appear to be small.

Adult↗