THE NEUROMUSCULAR BLOCKING ACTION OF PANCURONIUM IN MAN DURING ANAESTHESIA

The neuromuscular blocking action of pancuronium bromide wasinvestigated in anaesthetized patients. Pancuronium resemblestubocurarine in producing a competitive type block but is aboutfive times as potent as tubocurarine. With a small dose (0.02mg/kg) the onset of action of the drug was slow, with the timeto its maximum effect averaging 4.5 minutes. The maximum effectwas, on average, a reduction in twitch height of 69 per cent.With larger doses of the agent (0.05 mg/kg and 0.1 mg/kg) theonset was more rapid and usually a complete block was achieved.The recovery from 0.02 mg/kg and 0.05 mg/kg to 50 per cent ofthe initial twitch height averaged 12.2 minutes and 36.8 minutesrespectively. Repeated doses of the drug produced a greaterduration of action with a somewhat greater intensity of block.During recovery from the action of the drug a respiratory acidaemiareduced and a respiratory alkalaemia increased the rate of recovery. ^*Present address: Department of Anesthesiology, Columbia University,College of Physicians and Surgeons, New York, U.S.A.     

THE ACTION OF TACRINE ON NEUROMUSCULAR TRANSMISSION: A COMPARISON WITH HEXAFLUORENIUM

The action of tacrine has been studied in man, in the cat, andin vitro on a frog nerve-muscle preparation. The study showsthat tacrine possesses both anticholinesterase and neuromuscularblocking actions. In contradistinction to hexafluorenium, tacrinedoes not potentiate the neuromuscular blocking action of suxamethoniumat the neuromuscular junction. For this reason, in the intactanimal, the potentiation of the blocking action of suxamethoniumby tacrine pretreatment must depend largely on the capacityof this drug to inhibit plasma cholinesterase.     

POLYMYXIN B AND HEART MUSCLE

The effects of the polypeptide antibiotic, polymyxin B, on myocardialcontractility were studied in the isolated rat heart muscle.Five different doses of polymyxin B were tested. There wereno changes in contractility with doses ranging from the clinicaltherapeutic value to three times greater. There was an initialincrease and then depression with a dose six times greater thanthe therapeutic dose. There was no direct competitive interactionbetween polymyxin B and halothane or Ca²⁺. This suggests thatpolymyxin B does not depress the myocardium in clinical dosesand does not interfere with Ca²⁺ influx at the myocardial cellmembrane.     

Cell Processes in Basal Cell Carcinoma

Three cell process types are described in basal cell carcinoma. The most abundant are thin processes resembling microvilli; thick processes, mesa-like structures often surmounted by desmosomes; and large bulging processes. Processes occur in the intercellular spaces, and are more numerous in spinocellular cells than in basaloid cells. Despite the abundance of processes in basal cell carcinoma, they do not usually penetrate the basal lamina border of the tumor. This behavior differs from more rapidly invasive squamous cell carcinoma where processes extend through the fragmenting basal lamina into the stroma.     

Hexokinase kinetics in human skeletal muscle after hyperinsulinaemia,hyperglycaemia and hyperepinephrinaemia

The effects of 120 min of euglycaemic hyperinsulinaemia (UH, ∽ 5 mM; 40 mU m^-2 min^-1), UH plus adrenaline infusion (0.05 μgkg^-1 min^-l), and hyperglycaemic normoinsulinaemia (26 mM) on hexokinase kinetics in human skeletal muscle were examined. Biopsies were obtained from the quadriceps femoris muscle before and after each clamp. Total muscle hexokinase activity (HK_t) (measured on a 2500 g supernatant) at a saturating level of the substrate glucose (1 mM) averaged 13 mmol kg dry wt^-: min^-1 in the basal state and did not change significantly under any condition. Soluble hexokinase activity (HK_S) (16000 g supernatant) accounted for ∽ 65% of HK_t in the basal state, and this percentage was not significantly affected by any condition, suggesting that there was no major transfer of HK between cytosol and mitochondria. The activity of HK, and HK_s was inhibited by glucose 1,6-bisphosphate (G-l,6-P₂) in a concentration dependent manner in the basal state, and the sensitivity to Gl,6-P₂ inhibition was not altered by any condition. The activity of HK, and HK₈ in the presence of a subsaturating level of glucose (0.1 mM) accounted for ∽ 70% of the activity at 1 mM glucose, and this percentage was not altered by any condition. These data suggest that under the present conditions alterations in the rates of whole body glucose disposal cannot be associated with alterations in HK distribution between cellular compartments nor its measured kinetics properties.