Effectiveness of oral pyridostigmine pretreatment and cholinolytic-oxime therapy against soman intoxication in nonhuman primates.

Nonhuman primates which were fed Mestinon (pyridostigmine) syrup-impregnated food biscuits (40 mg per animal) exhibited a reproducible inhibition of whole blood cholinestrase activity of 40 to 50% for a period of 1 to 6 hr. Pyridostigmine pretreatment was supplemented by therapy with two doses of an antidotal combination (A,TM,B) consisting of 0.05 mg/kg atropine, 2.24 mg/kg TMB-4, and 0.4 mg/kg benactyzine which assured survival in five of six animals following three separate exposures to 10 LD50 soman. The protective period of this oral dose of pyridostigmine supported by A,TM,B therapy was between 1/2 and 8 hr. Oral pyridostigmine pretreatment in combination with atropine therapy (three doses of 0.07 or 1.00 mg/kg im) also saved monkeys exposed to 10 LD50 soman; however, the period of recovery was prolonged. Oral pyridostigmine pretreatment did not alter the lethality of soman in the absence of A,TM,B or atropine therapy.

The effects of blood flow and detoxification on in vivo cholinesterase inhibition by soman in rats.

The in vivo time course of cholinesterase inhibition was measured in brain, lung, spleen, hind limb skeletal muscle, diaphragm, intestine, kidney, heart, liver, and plasma of rats receiving 90 micrograms/kg soman, im. This dose of soman produced severe respiratory depression and transient hypertension, but no significant changes in the cardiac output or heart rate of anesthetized rats. The rate and maximal extent of in vivo cholinesterase inhibition by soman varied widely among the tissues. Although cardiac output was unchanged by soman administration, the blood flow in heart, brain, and lung (bronchial arterial flow and arteriovenous shunts) was increased, whereas blood flow in spleen, kidney, and skeletal muscle was decreased. The relative importance of tissue blood flow, tissue levels of cholinesterase and acetylcholinesterase, and tissue levels of soman-detoxifying enzymes (diisopropyl-fluorophosphatase and carboxylesterase) in determining the in vivo rate and maximal extent of cholinesterase inhibition was examined by multiple regression analysis. The best multiple regression model for the maximal extent of cholinesterase inhibition could explain only 63% of the observed variation. The best multiple regression model for the in vivo rate of cholinesterase inhibition contained three independent variables (blood flow, carboxylesterase, and cholinesterase) and could account for 94% of the observed variation. Of these three variables blood flow was the most important, accounting for 79% of the variation in the in vivo rate of cholinesterase inhibition. This suggests that it may be possible to use a flow-limited physiological pharmacokinetic model to describe the kinetics of in vivo cholinesterase inhibition by soman.

Plasma free cyanide and blood total cyanide: a rapid completely automated microdistillation assay.

Techniques are presented which provide direct measurement of both free cyanide (CN-) in plasma and total CN- in whole blood. Loss of total CN- from blood is prevented by conversion to cyanmethemoglobin. Both free and total CN- are assayed by a completely automated method providing readout 17 minutes after sampling. No prior isolation technique is required and sensitivity is adjustable to cover a broad range of CN- concentrations from 1 to 4000 uM. Precision of blood CN- values from 2 to 2500 uM is within +/- 2.3%. No interference results from thiocyanate or thiosulfate at a concentration of approximately 1 mM.

Cyanide loss from tissue baths in the presence and absence of tissue.

Loss of cyanide from Krebs-Henseleit solution (KHS) was studied in aerated tissue baths at 38 degrees C in the presence and in the absence of tissue. The rate of cyanide loss was greater from 300-microM than from 30-microM solutions and still greater from 300-microM solutions in the presence of vascular tissue. Initial cyanide loss was much greater from the tissue-containing bath, and the half-time was shorter in the presence of tissue (54 min) than in its absence (98 min) in baths containing the same initial cyanide concentration (300 microM).

Colonoscopic decompression and intubation of the cecum for Ogilvie's syndrome.

Cecal distention due to pseudo-obstruction of the left colon may result in perforation or necrosis of the right colon with catastrophic consequences. This problem occurs in people who are ill from other causes; therefore, the mortality and morbidity is high in Ogilvie's syndrome whether treated operatively or nonoperatively. The treatment of choice has been tube cecostomy when cecal diameter exceeds 12 cm on supine films. Fiberoptic colonoscopy has provided a new treatment modality for this condition. The cecum can be decompressed safely in most cases. Recurrent distention can be avoided by transanal intubation of the cecum. A case is discussed, and the technique of cecal intubation is described.

Use of ureteral catheters in colonic and rectal surgery.

Injury to the ureters is a serious complication of colonic and rectal surgery. The experience of the authors with routine use of ureteral catheters to minimize this complication is reviewed. It was found that there are minimal complications associated with their use. Injuries to the ureters were not completely avoided. However, unrecognized injuries (except ischemia) did not occur.

A method of management of a circumferential villous tumor of the rectum.

A case is presented in which a very large circumferential villous tumor was totally removed transanally with complete anatomic and physiologic restoration. Large circumferential tumors of the rectum present formidable technical problems. They may be malignant. When they are benign, abdominoperineal resection can be avoided. A less radical procedure that may be employed with complete resection of the tumor and without stricture formation, is described briefly.

The stability of sarin and soman in dilute aqueous solutions and the catalytic effect of acetate ion.

The hydrolysis of aqueous solutions of organophosphonate compounds such as sarin and soman is a critical factor in biochemical and therapeutic studies. The ability to dilute and transport these compounds with assurance of their purity is imperative to the integrity of such studies. An enzymic method has been used to measure low levels of organophosphonates. Maximum stability data were determined in aqueous and isotonic saline solutions. Acetate ion was found to significantly accelerate hydrolysis.1

A completely automated fluorometric blood cyanide method: a specific assay incorporating dialysis and distillation.

Discrete blood samples can be assayed at a rate of 20/hr. By means of a double lumen catheter, venous or arterial blood can be monitored continuously.

Quantitative assay of physostigmine in human whole blood.

A quantitative assay for measuring physostigmine in human whole blood is described. Blood samples are maintained at 37 degrees, and cholinesterase activity is measured periodically. The time required for enzyme reactivation is related to physostigmine concentration. The precision of the method is within +/- 4% over a physostigmine concentration range of 0.5-5.0 x 10(-7) M.