Abel Díaz

Complications of Bothrops, Porthidium, and Bothriechis snakebites in Colombia. A clinical and epidemiological study of 39 cases attended in a university hospital

The clinical and epidemiological features, as well as complications presented by 39 patients with Bothrops, Porthidium and Bothriechis snakebites, are described. Patients were admitted during 1 year in 25 hospitals of Antioquia and Chocó and then, they were transferred to the Hospital Universitario San Vicente de Paúl in Medellín, 30 of them because of the presence of complications, eight because of lack of antivenoms and another one because of the desire of his relatives. Thirty--one (79.5%) of the patients were male, 13 (33.3%) children, 59% of them were bitten at the lower extremities, the majority (74.4%) by Bothrops asper. Twenty-one (53.8%) of the patients were initially attended by traditional healers and sought medical attention at the local hospitals after 2h in 87.2% of the cases. Edema (100%), hemorrhage (74.4%), blistering (38.5%) and necrosis (38.5%), were the local signs of envenomation, while blood coagulation alteration (79.5%), hematuria (74.4%), gingival bleeding (43.6%), hypovolemic shock (23.1%) and oliguria (23.1%), were the systemic signs of envenomation. The final grade of envenomation was severe in 29 patients (74.4%). Thirty patients (76.9%) had one or more complications of the envenomation: acute renal failure (ARF), 15 (38.5%); soft-tissue infection, 12 (30.8%); central nervous system (CNS) hemorrhage, 5 (12.8%); compartment syndrome, 3 (7.7%); soft--tissue hematomas, 6 (15.4%); and Abruptio placentae, one (2.6%). There were four deaths (10.3%), two from ARF and two from cerebral hemorrhage. Fourteen other patients (35.9%) had sequelae. The onset of serotherapy after 2h of the bite was associated with the occurrence of ARF and CNS hemorrhage (p=0.02), as well as the risk of death and sequelae (RR=2.5).

Snakebites and ethnobotany in the northwest region of Colombia. Part III: neutralization of the haemorrhagic effect of Bothrops atrox venom.

Thirty-one of 75 extracts of plants used by traditional healers for snakebites, had moderate or high neutralizing ability against the haemorrhagic effect of Bothrops atrox venom from Antioquia and Chocó, north-western Colombia. After preincubation of several doses of every extract (7.8-4000 microg/mouse) with six minimum haemorrhagic doses (10 microg) of venom, 12 of them demonstrated 100% neutralizing capacity when the mixture was i.d. injected into mice (18-20 g). These were the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); the whole plants of Pleopeltis percussa (Polypodiaceae), Trichomanes elegans (Hymenophyllaceae) and Senna dariensis (Caesalpiniaceae); rhizomes of Heliconia curtispatha (Heliconiaceae); leaves and branches of Bixa orellana (Bixaceae), Philodendron tripartitum (Araceae), Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae); the ripe fruits of Citrus limon (Rutaceae); leaves, branches and stem of Ficus nymphaeifolia (Moraceae). Extracts of another 19 species showed moderate neutralization (21-72%) at doses up to 4 mg/mouse, e.g. the whole plants of Aristolochia grandiflora (Aristolochiaceae), Columnea kalbreyeriana (Gesneriaceae), Sida acuta (Malvaceae), Selaginella articulata (Selaginellaceae) and Pseudoelephantopus spicatus (Asteraceae); rhizomes of Renealmia alpinia (Zingiberaceae); the stem of Strychnos xinguensis (Loganiaceae); leaves, branches and stems of Hyptis capitata (Lamiaceae), Ipomoea cairica (Convolvulaceae), Neurolaena lobata (Asteraceae), Ocimum micranthum (Lamiaceae), Piper pulchrum (Piperaceae), Siparuna thecaphora (Monimiaceae), Castilla elastica (Moraceae) and Allamanda cathartica (Apocynaceae); the macerated ripe fruits of Capsicum frutescens (Solanaceae); the unripe fruits of Crescentia cujete (Bignoniaceae); leaves and branches of Piper arboreum (Piperaceae) and Passiflora quadrangularis (Passifloraceae). When the extracts were independently administered by oral, i.p. or i.v. route either before or after an i.d. venom injection (10 microg), neutralization of haemorrhage dropped below 25% for all the extracts. Additionally, B. rosademonte and P. percussa extracts were able to inhibit the proteolytic activity of B. atrox venom on casein.

A randomized blinded clinical trial of two antivenoms, prepared by caprylic acid or ammonium sulphate fractionation of IgG, in Bothrops and Porthidium snake bites in Colombia: correlation between safety and biochemical characteristics of antivenoms.

A randomized blinded clinical trial was performed in 53 patients bitten by Bothrops sp. and Porthidium sp. in Antioquia and Chocó, Colombia, in order to compare the efficacy and safety of two antivenoms made of whole IgG obtained by either ammonium sulphate (monovalent anti-B. atrox) or caprylic acid (polyvalent) fractionation. Additionally, antivenoms were compared by electrophoretic and chromatographic analyses and anticomplementary activity in vitro. With a protocol of 2, 4 and 6 antivenom vials for the treatment of mild, moderate and severe envenomings, respectively, both antivenoms were equally efficient to neutralize the most relevant signs of envenoming and to clear serum venom levels in patients from the first hour and later on. Three patients with severe envenoming and initially treated with less than six vials on admission had persistent or recurrent venom antigenemia within 12-48 h. Monovalent antivenom fractionated by ammonium sulphate precipitation had higher amounts of protein aggregates and nonimmunoglobulin proteins than polyvalent antivenom fractionated by caprylic acid precipitation. Both antivenoms presented anticomplementary activity in vitro, being higher in the monovalent product. In agreement, monovalent antivenom induced a significantly higher incidence of early antivenom reactions (52%) than polyvalent antivenom (25%).

Snakebites and ethnobotany in the northwest region of Colombia: Part II: Neutralization of lethal and enzymatic effects of Bothrops atrox venom

Twelve of 74 ethanolic extracts of plants used by traditional healers for snakebites in the northwest region of Colombia, were active against lethal effect of Bothrops atrox venom when they were i.p. injected into mice (18-20 g). After preincubation of sublethal doses of every extract (0.5-4.0 mg/mouse) with 1.5 i.p. lethal dose 50% (LD50) (99.3 microg) of venom, seven of them demonstrated 100% neutralizing capacity within 48 h. These were the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); rhizomes of Renealmia alpinia (Zingiberaceae) and Heliconia curtispatha (Heliconiaceae); the whole plants of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans (Hymenophyllaceae); and the ripe fruits of Citrus limon (Rutaceae). The other five extracts showing partial neutralization (45-80%; 10-30% survival rate in the control group receiving the venom alone; P<0.05) were: leaves, branches and stem of Costus lasius (Costaceae); the whole plant of Sida acuta (Malvaceae); rhizomes of Dracontium croatii (Araceae); leaves and branches of Bixa orellana (Bixaceae) and Struthanthus orbicularis (Loranthaceae). When the extracts were independently administered per oral or i.p. route 60 min before an i.m. venom injection (204 microg=1.5 i.m. LD50), C. limon, T. elegans, B. orellana and T. rosea extracts had partial and significant neutralizing capacity against B. atrox venom lethal effect. C. limon extract was also partially effective when it was administered either i.v. 15 min before or i.p. 5 min after an i.m. venom injection. Three of the 12 extracts with anti-lethal effect (C. limon, D. croatii and S. acuta) were devoid of antiphospholipase A2 activity, when they were tested against one minimum indirect hemolytic dose of B. atrox venom (2 microg) in agarose-erythrocyte-egg yolk gels.

Ontogenetic variability of Bothrops atrox and Bothrops asper snake venoms from Colombia

The lancehead snakes Bothrops asper and Bothrops atrox inflict 70-90% of the 3000 bites reported every year in Colombia. In this work, the venoms of B. atrox from Meta (Villavicencio, 33 specimens) and B. asper from Antioquia (San Carlos, 45 specimens), all of them born in captivity, were obtained at different ages (0-6 months; 1, 2 and 3-years old) and compared in terms of their pharmacological and immunochemical characteristics. A conspicuous ontogenetic variability was observed in venom samples from both species. Venoms from newborn and juvenile specimens showed higher lethal, hemorrhagic, edema-forming and coagulant activities, whereas venoms from 3-year old specimens showed higher indirect hemolytic, i.e. phospholipase A2 activity, being more significant in the case of B. asper. SDS-polyacrylamide gel electrophoresis of whole venom for both species evidenced a predominance of high mol. mass bands in the venoms from specimens of <1 year of age, with a change towards bands having lower mol. mass as snakes aged. Gel filtration chromatography showed five peaks in the venoms of B. asper of <6 months and in those from 3-year old specimens. Venom of adult specimens showed a higher number of peaks with indirect hemolytic activity than venom of newborn specimens. Polyvalent antivenom produced in Costa Rica recognized all the bands of both venoms from specimens at all ages tested, when assayed by Western blotting.

Neutralization of the edema-forming, defibrinating and coagulant effects of Bothrops asper venom by extracts of plants used by healers in Colombia

We determined the neutralizing activity of 12 ethanolic extracts of plants against the edema-forming, defibrinating and coagulant effects of Bothrops asper venom in Swiss Webster mice. The material used consisted of the leaves and branches of Bixa orellana (Bixaceae), Ficus nymphaeifolia (Moraceae), Struthanthus orbicularis (Loranthaceae) and Gonzalagunia panamensis (Rubiaceae); the stem barks of Brownea rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); the whole plant of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans (Hymenophyllaceae); rhizomes of Renealmia alpinia (Zingiberaceae), Heliconia curtispatha (Heliconiaceae) and Dracontium croatii (Araceae), and the ripe fruit of Citrus limon (Rutaceae). After preincubation of varying amounts of each extract with either 1.0 microg venom for the edema-forming effect or 2.0 microg venom for the defibrinating effect, the mixture was injected subcutaneously (sc) into the right foot pad or intravenously into the tail, respectively, to groups of four mice (18-20 g). All extracts (6.2-200 microg/mouse) partially neutralized the edema-forming activity of venom in a dose-dependent manner (58-76% inhibition), with B. orellana, S. orbicularis, G. panamensis, B. rosademonte, and D. croatii showing the highest effect. Ten extracts (3.9-2000 microg/mouse) also showed 100% neutralizing ability against the defibrinating effect of venom, and nine prolonged the coagulation time induced by the venom. When the extracts were administered either before or after venom injection, the neutralization of the edema-forming effect was lower than 40% for all extracts, and none of them neutralized the defibrinating effect of venom. When they were administered in situ (sc at the same site 5 min after venom injection), the neutralization of edema increased for six extracts, reaching levels up to 64% for C. limon.

A randomized double-blind clinical trial of two antivenoms in patients bitten by Bothrops atrox in Colombia

Abstract A randomized double-blind clinical trial in 39 patients envenomed by Bothrops atrox in Antioquia and Choco, Colombia, was performed to compare the efficacy and safety of 2 equine-derived antivenoms prepared at Instituto Clodomiro Picado, University of Costa Rica. Twenty patients received a monovalent anti- B , atrox antivenom (group A) and 19 patients were treated with a polyvalent (Crotalinae) antivenom (group B). Both antivenoms were equally efficient in the neutralization of the most relevant signs of envenoming (haemorrhage and blood clotting time alteration). Fourteen patients (36%) presented early adverse reactions to antivenoms and no significant difference between the 2 groups was observed. Urticaria (18%) was the most frequent early adverse reaction and there was no life-threatening anaphylactic reaction. Based on clinical criteria and serum venom levels, estimated by an enzyme immunoassay, 15 patients were classified into 2 groups: mild and moderate/severe envenoming. With the antivenom doses used in this study (3, 6 and 9 vials for mild, moderate and severe envenoming, respectively), both antivenoms were equally efficient in clearing serum venom levels within the first hour of treatment, and the levels remained below the lower limit of venom detection for 24 h. Antivenom concentration in serum remained high for up to 24 h after antivenom infusion, suggesting that an excess of antibody in relation to circulating antigen had been administered.

Inhibition of the Toxic Effects of Lachesis muta, Crotalus durissus cumanensis and Micrurus mipartitus Snake Venoms by Plant Extracts

The ethanol extracts of eight plants utilized against snakebites by traditional healers in Colombia (Pleopeltis percussa, Trichomanes elegans, Brownea rosademonte, Tabebuia rosea, Heliconia curtispatha, Bixa orellana, Renealmia alpinia and Citrus limon) were examined for their possible inhibitory ability against the venoms of Lachesis muta, Crotalus durissus cumanensis, and Micrurus mipartitus. Extracts were preincubated with 1.5 LD50 of each venom, and injected by the intraperitoneal route, in mice. Under these conditions, the lethal effect of L. muta venom was neutralized by all of the extracts, whereas C. d. cumanensis and M. mipartitus venoms were inhibited by six extracts, exceptions being P. percussa and C. limon. In addition, the myotoxic activity of C. d. cumanensis venom was neutralized by the extracts of H. curtispatha, B. rosademonte, P. percussa, and T. elegans. The neutralizing ability of the plant extracts was also evaluated by independent administration experiments. Extracts were injected by intravenous or i.m. (in situ) routes, immediately after the i.p or i.m. injection of 1.5 LD50 of venom, respectively. Under such conditions, their neutralizing efficacy was significantly reduced, and in some cases disappeared. Nevertheless, in situ administration of B. rosademonte, H. curthispatha, P. percussa, and T. elegans extracts still caused a partial but significant inhibition of the lethal effect of C. d. cumanensis venom, and the first three extracts reduced significantly the development of myonecrosis. These results identify useful plant species for future purification of venom-neutralizing components that might become helpful in the development of supplementary therapies against snakebites.

Routine chest roentgenogram after central venous catheter insertion is not always necessary

BACKGROUND To evaluate the usefulness of routine radiologic control after the insertion of a central venous catheter as a tool that might modify treatment of patients. METHODS A prospective study was made of 149 patients submitted to central venous catheter insertion. RESULTS In 55% of the patients the roentgenogram showed an adequate placement of the catheter tip and in 3.6% it showed some abnormal finding. Ten modifications were carried out based on the radiologic results. The prolonged partial thromboplastin time value and the subjective degree of difficulty showed a statistical relation to the appearance of complications. The number of punctures above one related to abnormal radiologic findings. CONCLUSIONS The results suggest that routine chest radiology after the insertion of a central venous catheter is not always necessary and that it should be ordered selectively, according to the findings made during the procedure and the subjective degree of difficulty.

Asociación entre la ingesta de nutrientes hematopoyéticos y el origen nutricional de la anemia en mujeres en edad fértil en Colombia

OBJECTIVES Compare the nutritional origin of anemia by sociodemographic variables and analyze its association with deficient hematopoietic nutrient intake. METHODS The database of Colombias 2005 National Survey of Nutritional Status was used. The data were obtained through complex representative sampling of the population and processed using SPSS v.15. Anemic women of childbearing age were selected and divided into two groups according to serum ferritin levels. Their customary hematopoietic nutrient intake and risk of deficiency were determined. The proportions of anemia types were compared by sociodemographic variables using the F-distribution, the Rao-Scott second order correction (P < 0.05). The association between the origin of the anemia and classification of the nutrient was analyzed using the odds ratio (OR). RESULTS SAMPLE 595 women. Non-hypoferric anemia (67.2%) predominated, with no statistical difference by sociodemographic variable, except in the Pacific region (hypoferric anemia, 52.1%). The prevalence of deficiency in the customary intake of hematopoietic nutrients was high. There was no significant association between the deficit in consumption and the origin of the anemia. CONCLUSIONS Non-hypoferric anemia was most common, with no difference by sociodemographic indicators except in the Pacific region. All the women were at high risk of deficiency in their customary hematopoietic nutrient intake, but a statistically significant association between the deficiency and the origin of the nutritional anemia was not observed. Programs to improve nutrient intake and a continued search for causes of nutritional anemia other than iron deficiency are justified.