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A rapid, sensitive gas chromatographic head-space method was developed for assay of biologic fluids for formic acid by its conversion to methyl formate. The flame ionization detector employed was sensitive to about 0.5 mg/liter formic acid and linear to at least 1000 mg/liter. The coefficient of variation was 6% or less from 5 to 1000 mg/liter. The method has potential application to methanol poisoning.

Haemoperfusion has been used increasingly in treatment of patients with drug overdose. Blood is pumped from the patient through a column of adsorbent material and recirculated back to the patient. The adsorbent materials, activated charcoal and Amberlite XAD-4 resin, avidly bind particular drugs so that extraction from blood, including protein bound drug, is nearly complete. Activated charcoal removes both polar and nonpolar drugs and probably metabolites; Amberlite removes non-polar drugs better than charcoal but does not remove more polar drugs or polar metabolites. The haemoperfusion cartridge can be regarded as an extracorporeal clearance organ. Methodological issues in computing column clearance are discussed. The efficacy of haemoperfusion in removing a drug is determined by the relative magnitude of haemoperfusion and intrinsic body clearance, by volume of distribution, and by rate of movement of drug from peripheral tissues to the blood compartment. Haemoperfusion is most efficacious for drugs with low intrinsic clearance and a relatively small volume of distribution, such as phenobarbitone, theophylline, and tolbutamide. In contrast, haemoperfusion removes only a small fraction of drugs with high intrinsic clearance and large volumes of distribution, such as digoxin and amitriptyline. Drug overdose may influence pharmacokinetics of drugs such as salicylate, Phenytoin, and ethchlorvynol, making predictions and evaluation of haemoperfusion difficult. Clinical reports of haemoperfusion treatment for drug overdose indicate that haemoperfusion can effectively remove certain drugs and potentially significantly influence the clinical outcome, although the latter remains to be proven. Haemoperfusion is quite effective in removing phenobarbitone. Short and intermediate acting barbiturates are also removed in substantial quantity, but because of a larger volume of distribution they demonstrate rebound increase in blood concentrations with possible associated clinical deterioration, after haemoperfusion is completed. Haemoperfusion appears to be less effective for glulethimide because of the drug’s large volume of distribution, compared with barbiturates, and rebound appears to be an even more significant problem. Haemoperfusion may be useful in treating overdosage with ethchlorvynol or Phenytoin, particularly with high blood concentrations of drug, when the intrinsic clearance of the drug may be quite low due to non-linear metabolism. Salicylate can be removed by charcoal haemoperfusion, but no more effectively than can be effected with haemodialysis. The latter has the advantage of providing a means for fluid and electrolyte control and not requiring systemic heparinisation. Haemoperfusion does not substantially remove digoxin and tricyclic antidepressants compared with the total body burden because of the extremely large volumes of distribution. However, clinical responses during haemoperfusion for these types of overdose have been reported. Temporary reduction in the concentrations of these drugs in the brain or heart or removal of active metabolites might account for a discrepancy. Haemoperfusion is quite effective for removing theophylline, a drug with a small volume of distribution and moderate intrinsic clearance, and results in substantial clinical benefit. The major complication of haemoperfusion is thrombocytopenia with the potential risk of haemorrhage. Platelet counts are commonly halved during haemoperfusion and return to normal levels over 1 to 2 days.

Cholinesterase activity of the tapeworm was studied histochemically with the Koelle method, using acetylthiocholine and butyrylthiocholine as substrates, and biochemically with the Warburg technique, using acetylcholine, acetyl-β-methylcholine and butyrylcholine as substrates.Eserine.tetra-isopropylpyrophosphoramide (iso-OMPA), 1,5-bis (4-trimethylammonium-phenyl-phntan-3-one diiodide (BW 62 C 47) and 1,5-bis(4-allylmethyl-ammonium-phenyl) pentan-3-one diiodide (BW 284 C 51) were used as inhibitors.Both the histochemically and the biochemically demonstrable tapeworm cholinesterase activity was readily inhibited by low concentrations of eserine but resistant to the other inhibitors employed, whatever substrate was used.In this respect the tapeworm cholinesterase activity markedly differed from that in the human serum, the rat brain homogenate or the duodenum of the cat, which were used as reference sources of cholinesterase.The histochemical cholinesterase reactions obtained with acetylthiocholine and butyrylthiocholine, with or without iso-OMPA or BW 62 C 47, showed identical distributions, selectively limited to nervous ganglia, nerve trunks and nerve fibres of the worm, including those innervating the suckers.It is concluded that the tapeworm cholinesterase is distinct from mammalian acetylcholinesterase and non-specific cholinesterase, even if it is, like acetylcholinesterase, a selectively neuronal enzyme and inhibited by excess substrate.

SUMMARY Plasma lidocaine levels were studied in epileptics and control subjects after slow intravenous injection of 2 mg/kg. Two experiments were made on the epileptics: one when they were on their usual antiepileptic and/or sedative drugs and the other after phenobarbital treatment of 4 weeks' duration. The plasma lidocaine levels were somewhat lower in the epileptics than in the control subjects at 30 and 60 minutes after starting the lidocaine injection, and the differences were statistically significant. Phenobarbital treatment did not cause further lowering in the plasma lidocaine levels of the epileptics. It is concluded that patients who have taken phenobarbital or some other potential inducers of the microsomal drug-metabolizing enzymes may have a somewhat increased tolerance to the systemic effects of cumulative doses of licocaine. ZUSAMMENFASSUNG Bei Epileptikern und Kontrollpersonen wurden die Plasmakonzentrationen von Lidocain nach langsamer i.v. Injektion von 2 mg/kg untersucht. Bei den Epileptikern wurden zwei Untersuchungen angestellt: Eine unter der iiblichen antiepileptischen und/oder sedativen Therapie, die andere nach 4-wochiger Phenobarbitalbehandlung. 30 und 60 Minuten nach dem Beginn der Lido-caininjektion waren die Plasmakonzentrationen bei den Epileptikern etwas niedriger als bei den Kontrollpersonen; die Unterschiede waren statistisch signifikant. Die Phenobarbitalbehandlung fiihrte nicht zu einer weiteren Ver-minderung der Plasmakonzentrationen von Lidocain bei den Epileptikern. Es kann der Schluss gezogen werden, dass Patienten, die Phenobarbital oder einen anderen potentiellen Anreger der mikrosomalen drogenabbauenden Enzyme eingenommen haben, eine etwas erhohte Toleranz gegen die Systemwirkungen kumulativer Dosen von Lidocain haben durften.