Biomedical subjects
Publications and source records attributed to F E Russell.
This review treats the general biology, taxonomy, distribution and venom apparatus of the venomous snakes of Central America. Consideration has been given to the chemistry, pharmacology and immunology of the venom, and particular attention is dispensed to the clinical problem, including the treatment, of envenomations by these reptiles.
Snake venom poisoning is a medical emergency requiring immediate attention and the exercise of considerable judgment. Of the estimated 8,000 bites inflicted by venomous snakes in the United States each year, approximately 6,000 are treated with commercial antivenin. The only commercially available antivenin for North American Crotalidae envenomation is Antivenin (Crotalidae) Polyvalent (equine origin) (ACP; Wyeth Laboratories, Philadelphia, PA). A common complication is the high incidence of hypersensitivity reactions, occurring in more than 75% of patients treated with ACP. To minimize these side effects, a novel, affinity-purified, antigen binding fragment (Fab) antivenom (FabAV) for Crotalidae venom poisoning has been produced from the sera of sheep. The new product is Antivenin Polyvalent Crotalid (Ovine) Fab (Crotab; Therapeutic Antibodies, Inc., Nashville, TN). The current report compares the potencies in mice of FabAV and ACP against venom-induced lethality. The results indicate that FabAV is 3.1-9.6 times more potent than ACP for the prevention of lethality of the nine United States venoms tested. For one of the venoms, Crotalus viridis helleri, FabAV was efficacious while ACP was not.
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During the two years 1986 and 1987 83 cases of cryptosporidiosis were identified by the finding of oocysts in the faecal samples submitted to a single microbiology laboratory. There were 58 children and 25 adults. Cryptosporidiosis was the commonest cause of gastrointestinal infection identified in children and the third commonest overall. Spring and autumn peaks were identified. The main symptoms were diarrhoea (median 10 days), vomiting (median seven days), abdominal pain (median seven days) and fever (median three days). A variety of other less common symptoms were noted including reactive arthritis. Three cases occurred during late pregnancy and the puerperium. Contact tracing supported both person-to-person transmission and an animal origin for cases within the group. Cryptosporidiosis is shown to be an important cause of traveller's diarrhoea. The incubation period was from two to 11 days.
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Fibrolase, a blood clot-lysing enzyme, was isolated from the venom of the snake Agkistrodon contortrix contortrix using preparative scale isoelectric focusing in the recycling isoelectric focusing (RIEF) apparatus. Two sequential purifications, beginning with 1.0 g of whole, dried venom, were employed. A pH 6-8 range gradient effected the first separation. While 100% of the enzyme was recovered in three fractions, 43% (one fraction) had 70% purity. The second run was a refractionation of three, pooled fractions from the first run, in a 0.7 pH range gradient. Of the fibrolase in the venom, 63% was recovered in four fractions. One of these represented 29% of venom fibrolase, with 97% purity. Gel filtration chromatography removed most of the remaining, higher molecular weight contaminants of the RIEF-purified enzyme.
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Scombroid poisoning has become an almost world-wide medical problem. It is probably the most common cause of fish poisoning, although frequently misdiagnosed as "Salmonella infection'. While there remains some question as to the definitive etiology, there is little doubt that the poisoning is caused by the ingestion of certain mackerel-like fishes whose tissues have undergone a number of changes provoked by bacteria, and involving the conversion of histidine to histamine, potentiated by diamines. Improper storage of the fishes, usually at temperatures above 20 degrees C, appears to be the most important predisposing factor. The organisms most commonly involved are Proteus sp., Clostridium sp., Escherichia sp., Salmonella sp. and Shigella sp. Twenty-five cases of scombroid poisoning are presented. The clinical manifestations were very similar in most cases, consisting of: alterations in taste; anxiety; hyperemia, particularly of the face and neck; nausea; pruritus; headache; certain other symptoms and signs. Most patients responded to antihistamitics, and all cases were self-limiting.
Adult specimens of seven southern Pacific rattlesnakes (Crotalus viridis helleri), four northern black-tailed rattlesnakes (Crotalus molossus molossus), and six western diamondback rattlesnakes (Crotalus atrox) were housed under controlled light and temperature and milked of venom monthly for 20 months. Ambient conditions were modelled to simulate seasonal change. Weighed amounts of lyophilized venom from each snake were compared chronologically for variation in isoelectric focusing patterns, using natural and immobilized gradients. No variation in patterns was evident over this time period for any individual snake. However, intraspecific differences were obvious in the venom samples. The pattern seems indicative of a species, however, concentration of various protein constituents seems individual and genetically "fingerprinted'. Unlike other physiological functions that demonstrate cyclicity in response to temperature and photoperiod, concentration ratios of venom components appear to be constant regardless of external cues. These findings may further emphasize the medical importance of treating snakebite victims symptomatically as individuals. A variation exists in the components of venoms of any given species, as well as in the physiological sensitivities of humans to a venom.
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The dose of an antivenin required to neutralize a clinical case of venom poisoning, as well as determining the timing or need to initiate antivenin treatment, is frequently difficult to objectively ascertain. In this study, venom from the southern Pacific rattlesnake, Crotalus viridis helleri, was injected into 29 dog hind limb anterolateral compartments. A solution of C. v. helleri venom (15 mg/ml) was prepared using dessicated venom and saline; 0.2 ml were injected sub-fascially so that each of the compartments received 3 mg of venom. In one group no antivenin was given, in a second group four vials of antivenin were administered i.v. 1 hr post-injection, and in the final group eight vials of antivenin were administered i.v. 1 hr following venom injection. In all groups intracompartment pressures, limb girth and surface temperature were measured at regular intervals over the first 48 hr. In the group receiving eight vials of antivenin the intracompartment pressure reached a peak mean pressure of 49 mm Hg at 2 - 4 hr, and then rapidly fell. In those treated with none or four vials the pressure rose to 70 and 60 mm Hg, respectively, and remained elevated over the first 24 hr. The difference between the former and latter two groups is statistically significant. The findings indicate that the intracompartmental pressure, and presumably destructive damage of the venom, can be controlled by adequate levels of i.v. antivenin. Intracompartmental pressure measurements should be considered as an adjunct in the monitoring and decision-making processes for the treatment of patients bitten by rattlesnakes.
Polyacrylamide gel affinity chromatography was employed to isolate and purify antibodies to the antigens of the venoms of four rattlesnakes. The antivenins were studied for their neutralizing properties on a number of pharmacologic preparations. It was found that the purified antibodies (IgG) were more efficacious than the commercially prepared antivenin in neutralizing the lethal, cytolytic, hemorrhagic, platelet aggregating, and other deleterious effects of the venoms. In addition, the purified antibodies gave no evidence of producing anaphylaxis or anaphylactoid reactions in animals sensitized to horse serum. The proposed technique is also more simple than current production methods, is time-saving, and less expensive.
The distinction between venomous, potentially dangerous snakes and snakes considered to be harmless to humans is not always clear. A man was bitten by an assumed harmless pet snake, Rhabdophis subminatus (the red neck keelback), that had been obtained from a pet store. The patient experienced a severe coagulopathy with life-threatening hemorrhage unresponsive to transfusion. Since this snake frequently is sold legally in the United States, we wish to alert the medical community to its potential danger and to discuss the pathophysiological mechanism by which the coagulopathy was produced.