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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 1,045 records · Page 58Linked to original sources

Neuromuscular refractoriness during blockage of transmission. A quantitative study.

The effects of suxamethonium and tubocurarine on the refractoriness of neuromuscular transmission were studied in 21 anaesthetized adult subjects under various levels of neuromuscular block. The ulnar nerve was stimulated every 12 s with twin supramaximal stimuli 4 ms apart. At any level of block, the refractory fraction (the fractional decrement of the compound electromyographic response of the adductor pollicis to the second twin stimulus, relative to the response to the first) was used to quantify neuromuscular refractoriness. The magnitude of block was determined by the response to the first stimulus. Correlation between refractoriness and the degree of block was sought. Without block, neuromuscular transmission averaged 23% (SEM 4) refractory with this twin interval. The refractory fraction was increased markedly by suxamethonium, reaching 0.69 (SEM 0.1) at 50% block. Complete refractoriness occurred during 25--75% block in eight of 11 instances. Tubocurarine did not significantly alter refractoriness, paired responses to the twin stimuli decreasing proportionately during block.

Adult↗

Magnitude, dose-requirement and mode of development of tachyphylaxis to suxamethonium in man.

Tachyphylaxis to suxamethonium infused at a constant rate was studied in 15 surgical patients under enflurane-nitrous oxide-oxygen anaesthesia. The compound electromyographic response of the adductor pollicis muscle to stimulation of the ulnar nerve was monitored. A short-lasting and a long-lasting nearly steady state were observed in Phase I and in Phase II, respectively, during both of which a constant infusion resulted in a constant block. Tachyphylaxis occurred during the transition of phases, beginning after infusion of 1.4 +/- 0.6 (SD) mg kg-1 of suxamethonium, and 36 +/- 14 (SD) minutes of exposure. Tachyphylaxis peaked after 2.6 +/- 1.3 (SD) mg kg-1, and 72 +/- 38 (SD) minutes of exposure. The maximum gain in neuromuscular transmission from the initial maintenance level of block as the result of tachyphylaxis was 53 +/- 24 (SD) % of the control. The results are thought to reconcile previously reported conflicting clinical observations on tachyphylaxis.

Adult↗

Multipeaking of the compound electromyographic response to single nerve stimulus: its occurrence and prevention in an experimental model.

The compound electromyographic response to a single nerve stimulus was examined in the cat tibialis anterior muscle preparation, to determine the cause of and to find a method of preventing multipeaking of the waveform. Bundles of the sciatic nerve were separated and stimulated while the response was detected by unipolar electrodes and analysed with an instrument specifically designed for this purpose. It was found that the most cephalad bundle of the sciatic nerve at the sciatic notch innervated the tibialis anterior muscle and that restriction of stimulation to this bundle most readily rendered the response single-peaked. It is concluded that nerve-branching is a common cause, and therefore a straightforward alternative to "repetitive response of the muscle" as the explanation, of multipeaking of the neurally-elicited compound electromyogram. A method of eliciting and recording the compound electromyogram in the cat tibialis anterior model is described.

Animals↗

Multiple autotransplantation of rat mammary induced by 7,12-dimethylbenz[a]anthracene: brief communication.

Mammary tumors induced in outbred Sprague-Dawley rats by 7,12-dimethylbenz]a]anthracene were excised, cut into 1- to 2-mm3 pieces, and then autotransplanted sc along the mammary line at six sites. Following an average period of 20--30 days, these autografts grew to approximately 2 cm in diameter in 32 of 48 rats (67%). Autografts in the other 33% of the rats remained dormant. Mammary tumors transplanted into allogeneic hosts failed to grow. Tumors derived from autotransplantation were indistinguishable from their primary tumors with respect to their histologic features, the nature of hormone dependency, the content of estrogen receptors, and their ability to incorporate [3H]leucine. Furthermore, autotransplanted tumors derived from a single primary tumor varied little with regard to the preceding parameters; thus they provided an opportunity for serial sampling of individual tumors for repeated morphologic and biochemical evaluations.

9,10-Dimethyl-1,2-benzanthracene↗

Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin and beta-bungarotoxin.

Interactions of neuromuscular effects of edrophonium, alpha-bungarotoxin, and beta-bungarotoxin were studied in 12 chickens using the sciatic-gastrocnemius nerve-muscle preparation to elucidate the mechanism of action of each drug. Modification by the toxins of neuromuscular effects of edrophonium depended on the level of block pre-established by the toxins. Edrophonium-induced augmentation of muscle twitch ("facilitation") was decreased by both toxins. As the block reached 50 per cent, the facilitation was nearly abolished. Edrophonium-induced contracture of the muscle was blocked by alpha-bungarotoxin only. At 25 per cent block, it was no longer observable in five of six preparations. Beta-bungarotoxin enhanced the contracture. At complete block, the contracture reached 156 (SE 11, n = 6) per cent of control. The authors conclude that edrophonium facilitates neuromuscular transmission by a prejunctional mechanism and causes contracture of the chicken muscle by a post-junctional activation. The beta-bungarotoxin-blocked nerve-muscle preparation of the chicken is a model of acute denervation potentially useful for the study of drug effects on the postjunctional membrane.

Animals↗

Antagonism of polymyxin B-induced neuromuscular and cardiovascular depression by 4-aminopyridine in the anesthetized cat.

In an attempt to find a better antidote to polymyxin B-induced neuromuscular blockade, the authors tested 4-aminopyridine, 0.4--1 mg/kg, in ten anesthetized cats. The sciatic--tibialis anterior nerve--muscle preparation was used. The neuromuscular blockade was successfully reversed in all cats. Rapidity of reversal depended on the dose of 4-aminopyridine administered. At 0.6--1 mg/kg, reversal of the twitch response from 20 per cent of control to 80 per cent of control required 2.4 (SE, 0.5) min; to 100 per cent, 14.4 (SE, 3.7) min. An overshoot of the recovery of neuromuscular blockade of 6--10 hours' duration followed the reversal. The mechanical twitch response reached a peak of approximately 140 per cent of control at 2 hours. At a lower dosage, 0.4 mg/kg, two of three cats took more than an hour for complete recovery of the twitch response, and the overshoot was approximately 10 per cent of control. The hypotensive effect of polymyxin B was partially reversed, but the bradycardia was not. It is concluded that 4-aminopyridine is an effective antidote to polymyxin B-induced neuromuscular blockade in the cat.

Aminopyridines↗

Furosemide in hyaline membrane disease.

In a randomized clinical trial designed to evaluate the effect of diuresis on infants with hyaline membrane disease, seven infants were treated with furosemide (2 mg/kg intravenously) and five received 5% dextrose water in 0.225% sodium chloride (control group). Arterial blood gas analyses performed before and during the six hours after treatment showed no significant difference between control and treated infants. Urine output and urine sodium and calcium loss were significantly increased (P less than .05) in the infants receiving furosemide. The diuresis seemed to have no effect on left atrial size determined echocardiographically, whereas measurements of dynamic skinfold thickness suggested mobilization of subcutaneous water. One infant became seriously dehydrated and hypotensive secondary to a massive diuresis. We concluded that furosemide had a potent diuretic effect in infants with hyaline membrane disease but does not improve cardiorespiratory function acutely. This may be because of failure to mobilize pulmonary interstitial fluid in the time period tested. It may also be possible that the presence of pulmonary interstitial fluid does not play an important role in the impairment of gas exchange in the acute stage of hyaline membrane disease.

Carbon Dioxide↗

Elevated rate of 3H-uridine incorporation in regressing rat ventral prostate.

Ventral prostates from adult Sprague-Dawley rats were removed at intervals during the first 2 weeks postcastration. Incubation of tissue with 3H-uridine and 3H-leucine was performed to determine the incorporation rate of radioactivity into the RNA and protein fractions respectively. Prostatic wet weight and 3H-leucine incorporation rate into prostate protein diminished postcastration, whereas 3H-uridine incorporation rate remained relatively high. The data suggest that RNA synthesis is relatively active in comparison with other parameters during regression.

Animals↗

Partial inhibition of castration induced ventral prostate regression with actinomycin D and cycloheximide.

Sprague Dawley male rats were injected subcutaneously with either actinomycin D or cycloheximide in saline immediately after castration. Control animals received saline only. Treatment was repeated daily for 4 subsequent days, and 24 hr after the last injection rats were sacrificed by decapitation. Ventral prostates were dissected and weighed. Actinomycin D and cycloheximide administration significantly reduced the rate of prostatic weight loss in castrated rats; serum testosterone levels in the control and drug treated animals were comparable. Histologic studies of the prostates indicated that drug treated animals had more active epithelial cells than saline injected controls. These results indicate that the rate of prostatic regression induced by castration can be modified by drugs such as actinomycin D and cycloheximide.

Adrenal Cortex Hormones↗

Neuromuscular block by circulating D-tubocurarine residue following uptake and distribution.

Serum concentration of d-tubocurarine decreases rapidly after intravenous injection because of uptake and distribution. The circulating residue of an ED 50 dose of d-tubocurarine five minutes after injection will produce no block in a previously unexposed neuromuscular junction. To produce a 50 per cent block with the circulating d-tubocurarine residue in a previously unexposed neuromuscular junction requires an initial injection of 2.5 x ED 50 dose. Five minutes after a dose 5 to 6 times the ED 50, the plasma d-tubocurarine residue is sufficient to produce a total block.

Animals↗

Focal contracture following injection of succinylcholine in patients with peripheral nerve injury.

Focal muscle contracture in the limb following sytemic administration of depolarizing neuromuscular blocking agents have been demonstrated experimentally with transection or crush injury of the nerve, but has rarely been observed clinically in patients with partial peripheral nerve injury. Three cases of spastic response in the hand and wrist are described in patients with subclinical chronic, subacute, and acute nerve injury, to document the occurrence of this phenomenon under various circumstances.

Adult↗

Characteristics of nondepolarizing neuromuscular block: (I) post-junctional block by alpha-bungarotoxin.

The characteristics of neuromuscular block produced by alpha-bungarotoxin, a post-junctionally active polypeptide toxin purified from snake venoms, have been studied in vivo in 12 anaesthetized cats, using the sciatic nerve-tibialis anterior muscle preparation. The onset of the neuromuscular block was slow and without fasciculation. The block was persitently progressive. The time course of the block depended on the dosage. In general, 0.1 mg/kg of alpha-BuTX appeared to approximate the threshold dosage while 0.2 mg/kg completely eliminated the twitch response in 2-5 hours. No recovery was observed in 8-30 hours. Larger doses accelerated the progression of the block. During the block, tetanic contractions and train-of-four twitches did not fade. The post-tetanic twitches were markedly facilitated. The block was antagonized by edrophonium, neostigmine, pyridostigmine, and succinylcholine, but the antagonism was less effective and shorter-lasting than that observed on curare-block, and the block always resumed the projected progression. Attempts were made to explain the observed difference between alpha-BuTX- and dTc-induced neuromuscular blocks by the practically permanent nature of block and the purely post-junctional site of action of alpha-BuTX. It was concluded that a pure post-junctional block is not characterized by fade, which rather might be a pre-junctional effect of some nondepolarizing neuromuscular blocking agents like d-tubocurarine.

Animals↗

Lactate dehydrogenase isoenzymes in human prostatic fluid: an aid in recognition of malignancy?

A total of 1,435 specimens of prostatic fluid were collected from 1,076 patients by rectal massage. Lactate dehydrogenase isoenzymes in the fluid were separated by acrylamide disk electrophoresis and the ratio of lactic dehydrogenase-5/lactic dehydrogenase-1 was used as the parameter for the test. There were significant differences in the ratio among patients with a normal prostate, benign prostatic hyperplasia and prostatic carcinoma. The mean values of lactic dehydrogenase-5/lactic dehydrogenase-1 ratios were 0.48 +/- 0.09, 1.36 +/- 0.17 and 5.21 +/- 0.79, respectively. Of 30 patients with histological evidence of prostatic carcinoma 25 (85 per cent) had a ratio greater than 2 in the prostatic fluid. On the other hand the ratio was less than 2 in 50 of 57 men (88 per cent) with a histological diagnosis of benign prostatic hyperplasia devoid of inflammation. When prostatic fluid contained white blood cells a positive correlation was observed between the ratio and the number of white blood cells per microscopic field (r equals 0.289, p less than 0.001). The results indicate that a lactic dehydrogenase-5/lactic dehydrogenase-1 ratio exceeding 2 in the prostatic fluid in the absence of inflammation should be regarded as an indication of high risk of the presence of carcinoma of the prostate.

Aged↗

Absence of "recurarization" in patients with demonstrated prolonged neuromuscular block.

The possibility of "recurarization" after antagonism of the competitive neuromuscular block with anticholinesterases was studied. Observations were made on the time-course of the block in five patients at risk from recurarization because of multiple organ failure and who demonstrated unusually prolonged blockade. In none of these patients did the block recur. We conclude that, provided spontaneous recovery of neuromuscular transmission has made progress before the antagonism, and that the patient does not deteriorate or become exhausted afterwards, recurarization is unlikely.

Adult↗

Neuromuscular facilitation during train-of-four and tetanic stimulation in healthy volunteers: observations with half-refractory paired responses.

The compound electromyographic response of the thenar musculature was elicited by supramaximal stimulation of the ulnar nerve in 12 awake healthy volunteers. The half-refractory period of the neuromuscular transmission was determined. Twin stimuli separated by the half-refractory interval were repeated as a unit at 2 Hz and at 50 Hz. Thus two trains of responses, one beginning with a maximal response, the other with a half-maximal response, were obtained with each frequently of stimulation. Marked facilitation of the electromyographic response began with the train of stimulation, especially with tetanic stimulation. A secondary fade occurred occasionally. These changes were more remarkable in the train of half-refractory responses. We conclude that nerve stimulation facilitates neuromuscular transmission and deduce that the characteristic fade observed with a curariform block, rather than being an uncovered physiological phenomenon, is caused by tubocurarine and related drugs.

Action Potentials↗