PubMed Health⌕ Search

Biomedical subjects

Sean P Bush

Publications and source records attributed to Sean P Bush.

14 recordsLinked to original sources

Complement inactivating proteins and intraspecies venom variation in Crotalus oreganus helleri.

Complement inactivating properties were detected in venom from the southern California distribution of Crotalus oreganus helleri (Southern Pacific Rattlesnake). This activity showed strong geographic bias to the San Bernardino Mountain range, and venom from this area reacted strongly with Fraction 5 antiserum (AF5). However, venoms from the San Jacinto Mountain range, which have been previously shown to contain Mojave toxin, did not inhibit complement and did not react with AF5. AF5 has been previously shown to recognize a protease in C. scutulatus venom that inactivates complement, but the identity of this protein has remained unknown. Using a functional venomic approach, utilizing two-dimensional gel electrophoresis coupled with liquid chromatography and tandem mass spectrometry (LC/MS/MS), we have identified catrocollastatin and hemorrhagic toxin II (HT-2) as the primary proteins recognized by AF5. The information we present within this manuscript further illustrates the now well-known reality of intraspecies venom variation and the challenges faced in providing comprehensive polyvalent antivenoms.

Animals↗

Verified bites by yellow sac spiders (genus Cheiracanthium) in the United States and Australia: where is the necrosis?

Spiders of the genus Cheiracanthium are frequently reported in review articles and medical references to be a definitive cause of dermonecrosis or necrotic arachnidism in humans. We provide 20 cases of verified bites by Cheiracanthium spiders from the United States and Australia, none with necrosis. A review of the international literature on 39 verified Cheiracanthium bites found only one case of mild necrosis in the European species C. punctorium. The basis for the suggestion that this spider genus causes dermonecrosis seems to be mostly inference from venom experiments in rabbits and guinea pigs, circumstantial spider involvement in human skin lesions, and repetitive citation of non-definitive reports in the medical literature. We discuss factors that lead to the erroneous elevation of virtually innocuous spiders to that of significant medical concern, which is a recurring problem in the medical community.

Adolescent↗

Mojave toxin in venom of Crotalus helleri (Southern Pacific Rattlesnake): molecular and geographic characterization.

Mojave toxin (MT) was detected in five of 25 Crotalus helleri (Southern Pacific rattlesnake) sampled using anti-MT antibodies and nucleotide sequence analysis. All of the venoms that were positive for MT were collected from Mt San Jacinto in Riverside Co., California. Since this population is geographically isolated from C. scutulatus scutulatus (Mojave rattlesnake), it is unlikely that this finding is due to recent hybridization. MT concentration differences between C. helleri and C. s. scutulatus reflected the presence of 'isoforms' of the toxin in the venom. Whereas C. s. scutulatus generally has several isoforms of the toxin (detected by Western blotting), only one 'isoform' that focused at pI 5.1 was detected in C. helleri. Both acidic and basic subunits of MT sequences were obtained from C. helleri DNA with primers specific for MT, but only from snakes that had MT in their venom. The sequence identity of the C. helleri acidic subunit to the C. s. scutulatus subunit was 84.9%, whereas the sequence identity of the C. helleri basic subunit was 97% to the C. s. scutulatus basic subunit. Using casein, fibrin, and hide powder azure as substrates, assays for proteolytic activity suggested that C. helleri possesses several different types of metalloproteinases in their venom. However, proteolytic activity was not detected, or present in reduced amounts, in specimens having MT. Clinical neurotoxicity following envenomation by certain populations of C. helleri may be due to MT.

Animals↗

Initial experience with Crotalidae polyvalent immune Fab (ovine) antivenom in the treatment of copperhead snakebite.

STUDY OBJECTIVE: Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) effectively treats patients bitten by rattlesnakes. The copperhead snake (Agkistrodon contortrix) caused 37% of venomous snakebites reported to US poison centers in 2001 and is the major envenomating reptile in the southeastern United States. FabAV has not been tested in human beings envenomated by copperhead snakes. METHODS: In this preliminary study, we performed a retrospective chart review of all copperhead snake envenomations reported to the Carolinas Poison Center that were treated with FabAV. Progression of limb swelling, coagulopathy, and hemodynamic status before and after FabAV administration, adverse effects of FabAV therapy, and recurrence phenomena were recorded. RESULTS: Of approximately 400 copperhead envenomation cases reported to the poison center during the study period, 32 received FabAV and were included. Most patients had moderate envenomation. The median time to FabAV administration was 4.0 hours. The median time to achieve initial control was 1.0 hour, with a median dose of 4 vials of FabAV. A rapid initial response, defined as cessation of the progression of local tissue injury within 4 hours of FabAV administration, occurred in 28 cases (88%; 95% confidence interval [CI] 76% to 99%). Four cases (13%; 95% CI 1% to 24%) were considered treatment failures. Recurrent swelling occurred in 6 cases (19%; 95% CI 5% to 32%). The incidence of recurrent swelling was not reduced by administration of repeated doses of antivenom on a planned schedule. One patient developed late-onset coagulopathy. One minor allergic reaction was observed. CONCLUSION: In this select group of patients bitten by copperhead snakes, local tissue effects of envenomation halted promptly after FabAV treatment in most cases. Treatment failures occurred, and recurrence of swelling and defibrination syndrome was sometimes problematic. Time to return to work and long-term limb function were not assessed. A controlled trial with long-term follow-up is needed to define the role of FabAV treatment for copperhead envenomation.

Adolescent↗

Pressure immobilization delays mortality and increases intracompartmental pressure after artificial intramuscular rattlesnake envenomation in a porcine model.

STUDY OBJECTIVES: We determine the effect of pressure immobilization on mortality and intracompartmental pressure after artificial intramuscular Crotalus atrox envenomation in a porcine model. METHODS: We prospectively studied 20 pigs using a randomized, controlled design. After anesthesia, C atrox venom (20 mg/kg) was injected with a 22-gauge needle 10 mm deep into the tibialis anterior muscle of the hind leg. Pigs were randomized to receive either pressure immobilization (applied 1 minute after envenomation and maintained throughout the duration of the experiment) or no pressure immobilization. We measured time to death, intracompartmental pressure before venom injection and at 2 hours after injection, and leg circumference at a standardized location before injection and immediately postmortem. Duration of survival was compared using Kaplan-Meier survival analysis. RESULTS: The dose of venom resulted in 100% mortality. The median survival was longer in the pressure immobilization group (191 minutes, range 140 to 240 minutes) than in the control group (median 155 minutes, range 119 to 187 minutes). The difference between the groups was 36 minutes (95% confidence interval [CI] 2 to 64 minutes; P =.0122). The mean intracompartmental pressures were 67+/-13 mm Hg+/-SD with pressure immobilization and 24+/-5 mm Hg without pressure immobilization. The difference between groups was 43 mm Hg (95% CI 32 to 53 mm Hg). The mean circumferences were 14.3 cm in the pressure immobilization group and 19.1 cm in the control group. The difference between groups was -4.8 cm (95% CI -5.7 to -3.9 cm). CONCLUSION: Compared with control animals without treatment, the pressure immobilization group had longer survival, less swelling, and higher intracompartmental pressures after artificial, intramuscular C atrox envenomation in our porcine model.

Animals↗

Why no antivenom?

Explore the source record for details and available documents.

Acute Disease↗

Reports of presumptive brown recluse spider bites reinforce improbable diagnosis in regions of North America where the spider is not endemic.

Envenomations by the brown recluse spider have been reported throughout North America, despite the fact that the spider's range is limited to the South and central Midwest of the United States. Several of these medical reports have originated from regions of nonendemicity where the spider has never or rarely been documented and brown recluse spider populations are unknown. In most of these reports, no spider is positively identified in association with the dermonecrotic wound, and diagnosis has been based on clinical examination findings. Considering the extreme rarity of brown recluse spiders in areas of nonendemicity, the diagnosis of a presumptive bite is a misdiagnosis that reinforces the assumption that brown recluse spiders are common local etiologic agents of necrosis. There are many medical conditions of diverse origin that have been misdiagnosed as brown recluse spider bites, some of which can be fatal or debilitating. Physicians' awareness of these conditions will increase diagnostic accuracy in areas of North America where bites from brown recluse spiders are improbable.

Diagnostic Errors↗

Crotalidae polyvalent immune Fab (ovine) antivenom is efficacious for envenomations by Southern Pacific rattlesnakes (Crotalus helleri).

STUDY OBJECTIVE: Southern Pacific rattlesnake (Crotalus helleri ) venom is not 1 of the 4 venoms used to produce Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV). There is currently no published clinical experience regarding the efficacy of this new antivenom for confirmed C helleri envenomation, and animal data suggest greatly diminished efficacy. We assessed the efficacy of FabAV for patients with confirmed C helleri envenomation. METHODS: We conducted a prospective observational study of 23 consecutive rattlesnake envenomations that were treated with FabAV at our center. Patients were excluded if the species of snake could not be confirmed, if FabAV antivenom was not given, or if Antivenin (Crotalidae) polyvalent (equine) was given. We collected serial physical examination and laboratory data over a 24-hour period to serially evaluate the severity score and performed follow-up to evaluate delayed reactions. RESULTS: There were 15 patients who received FabAV and had the species of rattlesnake confirmed (9 C helleri, 4 C scutulatus scutulatus, 1 C mitchellii pyrrhus, 1 C ruber ruber ). C helleri envenomations demonstrated similar improvement in serial snakebite severity scores to those of other species. Three patients treated with scheduled dosing had recurrence of progressive swelling (2 C helleri and 1 C mitchellii pyrrhus ) during the 24-hour study period. CONCLUSION: We observed similar improvement in FabAV-treated patients with C helleri envenomation compared with those of other species and conclude that this treatment in standard doses appears efficacious for bites by this species. Progressive swelling may recur despite scheduled dosing.

Animals↗

Crotaline Fab antivenom for the treatment of children with rattlesnake envenomation.

OBJECTIVE: There is little data regarding safety or efficacy of Crotalinae polyvalent immune Fab (ovine) antivenom (crotaline Fab) in pediatric patients. Our objective was to provide the first information regarding safety and effectiveness of this new drug in children. METHODS: Data were collected prospectively and retrospectively for all consecutive pediatric patients bitten by rattlesnakes and treated at 2 urban hospitals during 2001. Cases were included if there were signs of envenomation at presentation, patient age was 13 years or less, and there was administration of crotaline Fab. Cases were excluded if antivenin (Crotalidae) polyvalent (equine origin, the conventional antivenom) was given. Primary outcome variables were snakebite severity scores throughout the course of therapy, number of vials of crotaline Fab administered, occurrence of allergic reactions, adjunct surgical therapy, and the presence of permanent sequelae or serum sickness identified at follow-up. RESULTS: In the 12 cases studied, ages ranged from 14 months to 13 years (mean: 6.9; standard deviation: 4.2). Presentation snakebite severity scores ranged from 2 to 9 (mean: 5.3; standard deviation: 2.3). Total crotaline Fab doses ranged from 4 to 22 vials (mean: 12.7; standard deviation: 5.4). Initial control of symptoms was achieved with 4 to 16 vials (mean: 7.7; standard deviation: 3.7), and severity scores stabilized or improved within 24 hours in all patients. Recurrence of local swelling occurred in 1 case despite scheduled repeat doses of antivenom. No cases required surgical intervention, and no permanent sequelae were identified. No immediate or delayed hypersensitivity reactions occurred. CONCLUSION: In this group of pediatric patients treated for rattlesnake envenomation, crotaline Fab antivenom was safe and seemed to be effective.

Adolescent↗