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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 1,063 records · Page 59Linked to original sources

Absorption and protein binding of N-2-fluorenylacetamide and its metabolites in the bladder of rabbit.

To assess the reactivity of a bladder carcinogen, the absorption by the rabbit (male New Zealand White) bladder mucosa of N-2-acetylaminofluorene (AAF), N-hydroxy-2-acetyl-aminofluorene (N-OH-AAF), and the N-O-glucuronide of AAF (N-OGI-AAF), as well as binding to the protein and RNA of bladder mucosa, was measured in vivo and in vitro. Mucosal pieces incubated for 3 hours in medium containing a carcinogen demonstrated that the fluorene nucleus of both AAF and N-CH-AAF bound equally with cellular proteins, while N-OGI-AAF binding was lower. In the presence of an excess of beta-glucuronidase, however, N-OGI-AAF showed binding equivalent to its metabolic precursor. After a 3-hour instillation into the bladder lumen of radioactive carcinogens suspended in urine in vivo, transmural absorption of AAF and N-OH-AAF (90%) was substantial, while N-OGI-AAF was absorbed less (55%). The renal excretion during this period varied from 18 to 52% of the instilled radioactivity. There was little reactivity of these carcinogens with the mucosal RNA, both in vivo and in vitro. The metabolism of N-OH-AAF and N-OGI-AAF was such, both in vitro and in vivo, that the acetyl group was not included in the final protein-carcinogen complex in what appeared to be an enzyme reaction.

2-Acetylaminofluorene↗

Inhibition of leukocyte migration by tumor-associated antigen in soluble extracts of human hepatoma.

The leukocyte migration inhibition assay was used to detect cell-mediated immune reaction of hepatoma patients. Extraction of 3 pairs of human hepatoma tissue and normal liver tissue was made by 3 M KCI solution, and soluble hepatoma antigens were used to test against leukocytes of 18 hepatoma patients by the leukocyte migration inhibition assay. In all, 25 tests were performed; most of them were allogenic, and only 3 tests were autologous. Migration inhibition was observed in 13 of 25 tests, and there were only a few cases of migration inhibition in the control groups. It was concluded that tumor-associated antigen of human hepatoma was contained in the 3 M KCI extract of hepatoma tissue and that tumor-associated antigen of human hepatoma was shared by some hepatoma patients.

Antigens, Neoplasm↗

Some characteristics of neuromuscular block in the respiratory musculature in anaesthetized man.

The ability to breathe against a mild expiratory obstruction was examined in 64 adult patients under halothane-nitrous oxide-oxygen anaesthesia. The trachea of all patients were incubated. It was found that d-tubocurarine 0.11 mg/kg blocked the respiratory musculature by 50 per cent. The onset of block was immediate, with the peak effect reached within one minute. The duration of block was either very short (1 to 2 minutes) or long (paralleling the blockade in the thumb twitch), depending upon the dose of d-tubocurarine. Following injection of a small dose (up to 0.1 mg/kg) the respiratory musculature might be blocked by 30 per cent but for only one minute, disproportionately short as compared with the thumb twitch. Following injection of a large dose (0.1-0.3 mg/kg) the duration was long, but the recovery was only slightly ahead of the thumb. Following an intermediate dose, a biaphasic pattern was observed. An initial partial recovery was observed during the first 1 to 2 minutes. Comparison of the respiratory musculature and the thumb twitch revealed that the respiratory musculature was highly sensitive to block and has a different time course. Succinylcholine 0.08 mg/kg blocked the respiratory force by 50 per cent with a time course similar to the block in the thumb twitch. The clinical significance of these observations are discussed.

Abdominal Muscles↗

Neuromuscular block by neomycin in the cat.

The neuromuscular block produced by neomycin is unique. Despite nearly complete blockade of the twitch the tetanus is not blocked and does not fade. The pathognomonic post-tetanic exhaustion has not been reported previously. Anticholinesterases and calcium antagonize the block, but the antagonism may not be complete. Germine antagonizes the block in the cat, but its clinical value has not been tested. These characteristics of neuromuscular block by neomycin strongly suggest respiratory support and sedation to decrease the respiratory drive, rather than attempts at antagonism, as the rational management of patients suffering from toxic paralysis due to neomycin.

Anesthesia↗

Neuromuscular sensitivity to tubocurarine. A comparison of 10 parameters.

The pharmacometrics of neuromuscular block by tubocurarine was studied. Ten parameters were compared for the sensitivity, the scatter and the linearity of response at three levels of block in 11 cats. The fourth twitch of the train-of-four is the most sensitive parameter, followed in order of decreasing sensitivity by the train-of-four fade, the faded tetanus, the tetanus, the single twitch, the post-tetanic twitch and the tetanic fade. At the level of 50% block of the single twitch, all other parameters differ significantly (P less than 0.05) from the single twitch in sensitivity. With the exception of the tetanic fade, all parameters examined correlate with the single twitch (r xy = 0.42-0.77). This permits limited translation of results among various parameters. In cats the scatter of results is least for the most sensitive parameter, and vice versa. We conclude that the train-of-four is the most sensitive parameter, and that the single twitch is valid for an over-all estimation of the neuromuscular block induced by tubocurarine.

Animals↗

Self-antagonism: a possible mechanism of tachyphylaxis in suxamethonium-induced neuromuscular block in man.

Twelve adults receiving halothane-nitrous oxide anaesthesia for elective surgery were investigated during suxamethonium-induced neuromuscular block, using the train-of-four twitch for measurement of both the degree of block and the magnitude of fade (decrease in fourth-to-first ratio). The residual neuromuscular block resulting from prolonged exposure to suxamethonium could be antagonized by bolus injections of suxamethonium itself, in doses which increased the block in Phase I. When self-antagonism was demonstrated, larger doses were necessary to increase the residual block, but only after overcoming the self-antagonizing effect. A biphasic response, first antagonizing then increasing the block, was observed following injection of a single bolus of suxamethonium. The self-antagonizing effect was more obvious in the fourth twitch of the train-of-four, resulting in a marked decrease in train-fo-four fade (increase in train-of-four ratio). It was concluded that self-anatagonism may be an important cause of tachyphylaxis in suxamethonium-induced neuromuscular block in man.

Adult↗

Spontaneous recovery of the thumb twitch from neuromuscular block by suxamethonium in anaesthetized man.

The neuromuscular blocking effect of repeated bolus administration of suxamethonium 1 mg/kg was observed in 10 healthy surgical patients under enflurane-nitrous oxide-oxygen anaesthesia. Tachyphylaxis and slow recovery of the thumb twitch occurred in close dose-relationships with transition of Phase I block to Phase II, using train-of-four fade as an indicator of the transition. Failure of the thumb twitch to recover to 75% of control, and subsequent step-wise depression from additional doses of suxamethonium had a sudden onset shortly after establishment of marked train-of-four fade.

Adult↗

A model study of facial injury caused by impact while wearing an ophthalmic frame.

Damage to facial tissue caused by an ophthalmic frame when there is impact to the face was studied by means of a paraffin-covered mannequin head. Under mild conditions of impact it was easily observed that metal frames and metal components do more tissue damage than is done by a zylframe. A series of the commonly dispensed frames was compared for facial injury potential caused by impact to the face.

Biophysical Phenomena↗

Suppressive role of indole on 2-acetylaminofluorene hepatotoxicity.

Indole is known to suppress the hepatotoxicity and carcinogenicity of 2-acetylaminofluorene (AAF) in rats and hamsters. For elucidation of the mechanism of its protective role, 2 experiments were conducted using young male rats. In the 1st experiment, the 24-hr biliary excretion of N-hydroxy-2-acetylaminofluorene (N-OH-AAF)-glucuronide was measured after 2 and 4 weeks of dietary administration of 0.03% AAF with or without 1.6% indole. The amount of [9-14C]N-OH-AAF that was excreted as the glucuronide following a single i.p. injection of [9-14C]AAF was lower after 2 weeks in animals fed AAF and indole, as compared to those fed AAF alone [1.5 +/- 1.2% versus 19.6 +/- 3.6% S.E. (p less than 0.001)]. After 4 weeks of AAF administration without indole, the biliary excretion fell to 4.8 +/- 2.1%. This was also significantly higher than that of the animals fed both AAF and indole [1.8 +/- 1.2% (p less than 0.025)]. The suppressive role of indole on the conjugate excretion was also reflected in a decreased biliary excretion of all [9-14C]AAF metabolites in animals treated with indole alone. In the 2nd experiment, the protective action of indole was assessed by survival following daily i.p. injections of N-OH-AAF and Na2SO4 solution. Na2SO4 increased the hepatotoxicity of N-OH-AAF. Indole suppressed the toxicity of N-OH-AAF even in the presence of Na2SO4. This protective role of indole was partially overcome only when excess sulfate was coadministered. These results indicate that indole suppresses the biliary excretion of the O-glucuronide of N-OHAAF during the initial exposure of the animal to the carcinogen, possibly reflecting decreased N-OH-AAF formation. Indole also modifies the metabolism of AAF FOLLOWING N-hydroxylation, perhaps activating N-OH-AAF, depending upon the concentration of sulfate available.

2-Acetylaminofluorene↗