[Upper digestive hemorrhage and hepatic artery aneurysm].
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Biomedical subjects
Publications and source records attributed to A Díaz.
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Inverted nasosinusal papilloma is a benign tumor accounting for less than 4% of all nasal masses. The lesion originates in the mucosa lining the nasal cavities, the locations in decreasing order of frequency being the lateral wall of the nasal fossa, ethmoid sinus, and maxillary sinus; the sphenoid sinus is only rarely affected. Despite its benign histology, the tumor shows aggressive behavior and can be associated to carcinomas. Surgery is therefore indicated in such cases.
Catalase-1 (Cat-1), one of the two monofunctional catalases of Neurospora crassa, increases during asexual spore formation to constitute 0.6% of total protein in conidia. Cat-1 was purified 170-fold with a yield of 48% from conidiating cultures. Like most monofunctional catalases, Cat-1 is a homotetramer, resistant to inactivation by solvents, fully active over a pH range of 4-12, and inactivated by 3-amino-1,2,4-triazole. Unlike most monofunctional catalases, Cat-1 consists of 88 kDa monomers that are glycosylated with alpha-glucose and/or alpha-mannose, is unusually stable, and is not inactivated or inhibited by hydrogen peroxide. Cat-1 was more resistant than other catalases to heat inactivation and to high concentrations of salt and denaturants. Cat-1 exhibited unusual kinetics: at molar concentrations of hydrogen peroxide the apparent V was 10 times higher than at millimolar concentrations. Inactivation of Cat-1 activity with azide and hydroxylamine was according to first order kinetics, while cyanide at micromolar concentrations was a reversible competitive inhibitor.
Taenia solium cysticercosis seriously affects human health when localised in the central nervous system (CNS) and causes great economic loss in pig husbandry in rural areas of endemic countries. Increasing the resistance to the parasite in the obligatory host pig may help in curbing transmission. Three synthetic peptides based on protein sequences of the murine parasite Taenia crassiceps, which had previously been shown to induce protection in mice against homologous challenge, were tested as a vaccine against T. solium cysticercosis in pigs. Vaccinated and unvaccinated piglets (240 in all) were distributed in pairs among the peasants' households of two rural villages in Mexico in which 14% of the native pigs were cysticercotic. Ten to twelve months later, the effect of vaccination was evaluated at necropsy. Vaccination decreased the total number of T. solium cysticerci (98.7%) and reduced the prevalence (52.6%). The natural challenge conditions used in this field trial strengthen the likelihood of successful transmission control to both pig and human through a large-scale pig vaccination program. We believe this is a major contribution in anticysticercosis vaccine development as these rather simple yet protective peptides are potentially more cost-effective to produce and less variable in results than antigens that are more complex.
Mucopolysaccharidosis IIIA, also known as Sanfilippo syndrome type A, is an autosomal recessive storage disorder caused by deficiency of sulfamidase. The disease results in severe central nervous system degeneration often with mild somatic features that may delay the clinical diagnosis. Molecular analyses would allow early and unequivocal heterozygote detection, providing a useful tool for genetic counselling. About 40 mutations have been reported in the sulfamidase gene, with a very uneven distribution in different patient populations. We have previously described the high prevalence of mutation 1091delC in a small number of Spanish Sanfilippo A patients. The aim of the present work is to extend the mutational study to a total of 26 unrelated patients and perform haplotype analysis in order to study the origin of some mutations. The whole coding region of the gene was scanned by SSCP analysis and sequencing. This allowed the identification of 14 different mutations, corresponding to 90% of the mutant alleles. Seven of these mutations were only found in this Spanish group of patients, three of which, R150W, R433Q and R433W, are described here for the first time. We have also analyzed four internal polymorphisms and constructed the corresponding haplotypes. Chromosomes bearing mutation 1091delC show a conserved haplotype suggesting a common origin for this mutation. Moreover, all other mutations found twice or more also have conserved haplotypes for those polymorphic markers.
OBJECTIVE: The objective of this study was to analyze the incidence and significance of hepatic dysfunction after cardiac surgery in children. DESIGN: Prospective, observational study. SETTING: Pediatric intensive care unit of a university hospital. PATIENTS: The study consisted of 232 children ranging in age from newborn to 17 years with no history of liver disease. MEASUREMENTS AND MAIN RESULTS: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyltranspeptidase (GGT), alkaline phosphatase, total and conjugated bilirubin, blood glucose, urea, creatinine, and coagulation studies were determined at admission, at 24 and 48 hrs, and at 7 days. Hepatic dysfunction was taken as an ALT of > 100 IU/L or a moderate or high hepatic score. The statistical study included bivariate analysis and multivariate logistic regression to study the risk factors for hepatic dysfunction. Twenty-one patients (9%) showed an ALT > 100 IU/L, and 29.3% had a moderate or high hepatic score. A relationship was found between hepatic dysfunction and the type of cardiopathy (D-transposition of the great arteries and coarctation of the aorta), shock, the administration of dopamine or epinephrine, renal insufficiency, the presence of pulmonary changes (pulmonary edema, atelectasis, pulmonary hypertension, hypoxemia), hematologic disturbances (prothrombin time, kaolin-cephalin time, fibrinogen, and platelets), and the need for a greater number of transfusions of packed cells, plasma, and platelets. Compared with 7.6% of the rest of the patients (p <.001), 38% of patients with an ALT > 100 IU/L died. The hepatic score of those patients who died was 4.2 (2.3)-higher than that of the survivors at 1.5 (1.8), (p <.001). Shock and renal insufficiency were the factors most significantly related to the development of hepatic dysfunction. CONCLUSIONS: Hepatic dysfunction is an uncommon complication in children after cardiac surgery. This complication is related mainly to hemodynamic disturbances and renal insufficiency and is an indicator of poor prognosis.
A group of 32 annatto genotypes collected in five Venezuelan regions (Oriente, Centro, Llanos, Andes and Amazonas) and in Brazil were used for morphological studies. The fruit variables with the greatest discriminatory power in the formation of groups were capsule size, spinosity and seed size. On the other hand, an association group among the variables spinosity, spine length, dehiscence and apex shape were formed, also a proportional association between capsule and seed size, and between dehiscent capsule and brown coloured seeds. Additionally, in order to discriminate morphological variables behaviour in respond to electrophoretic variables, a group of protein and isozyme bands associated with fruit characteristics were established. Therefore, a classification system of this species was possible using morphological studies of the capsules, even though a determined association relating morphological and molecular patterns was not found.
In order to identify and to determine the genetic variability of 36 annatto genotypes (Bixa orellana L.) collected in five Venezuelan regions (Oriente, Centro, Llanos, Andes and Amazonas) and in Brazil, hydrosoluble protein patterns as well as specific isozyme patterns (alpha-esterase, beta-esterase and peroxidase) were studied using extracts of germinated annatto seeds with radicles of 10 to 15 mm long. Each electrophoretic system allowed genotype discrimination by means of unique banding patterns: both the hydrosoluble protein and the electrophoretic system of beta-esterase with nine banding patterns each; whilst alpha-esterase and peroxidase discriminated eight and three genotypes, respectively. On the other hand, a combination of all the systems permitted a greater discrimination since 34 out of 36 genotypes could be distinguished. Eight mayor groups were formed that showed high levels of genetic diversity (40 to 60%) with no association between geographic and genetic distances, probably because of human influence in the aleatory distribution of this crop. Results obtained indicated that using electrophoretic banding patterns, a classification system could be established for identification and genetic variability purposes in this species.
Vaccination of pigs of mixed genetic make-up, raised as rustically as done in rural Mexico, resulted in effective protection to experimental challenge against Taenia solium cysticercosis. Maximum protection was achieved if pigs were immunized at 70 days of age. There was large variation of viable parasite load within vaccinated pigs and controls, which is suggestive of significant genetic factors influencing susceptibility, besides immunization. Our results strengthen the advisability of pig vaccination for control of T. solium cysticercosis, since it lowers the number of viable cysticerci capable of transforming into tapeworms.
The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. In the majority of cancer patients, hypercalcemia appears to be a consequence of the tumor production of parathyroid hormone (PTH)-related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy, in contrast to those with primary hyperparathyroidism, have an uncoupled bone turnover, and they usually have low circulating levels of 1.25(OH)2D3. We performed a case-control study to assess the relationship of plasma PTHrP, PTH and 1.25(OH)2D3 with hypercalcemia in cancer patients with a variety of tumors. Sixty of these patients had hypercalcemia, and 45 were normocalcemic. We measured PTHrP and PTH by immunoradiometric assay (Nichols), and 1.25(OH)2D3 by radioreceptor assay (Nichols), in plasma in both groups of cancer patients. Using a logistic regression analysis, we found that the higher PTHrP in plasma, the higher association with hypercalcemia occurred in these patients. In addition, the decreased plasma levels of PTH and 1.25(OH)2D3 in the majority of cancer patients were found to be significantly associated with hypercalcemia. Our results indicate that the combined determination of PTH, PTHrP and 1.25(OH)2D3 in plasma represents a more comprehensive approach to the investigation of hypercalcemia in cancer patients. Our data also support the role of PTHrP as a humoral factor responsible for hypercalcemia in these patients.
Gaucher disease is the most prevalent sphingolipid storage disorder in humans caused by a recessively inherited deficiency of the enzyme glucocerebrosidase. More than 100 mutations have been described in the glucocerebrosidase gene causing Gaucher disease. Some of them are complex alleles with several mutations due to recombination events between the gene and its highly homologous pseudogene. The generation of these recombinant alleles involves, in most cases, a crossover in the 3' end of the gene, beyond exon 8. However, in a few cases recombination took place in a more upstream location. Here we describe the analysis of a patient with type I Gaucher disease who bears a new complex allele. This allele was originated by a crossover between the gene and the pseudogene at intron 2, the most upstream recombination site described so far, which gave rise to a fusion gene. The patient was first diagnosed as homozygous for the c.1226 A --> G (N370S) mutation but the early onset of the disease prompted us to perform parental DNA analysis which showed that the mother was not a N370S carrier, suggesting deletion of at least part of the gene. Molecular analysis of the complex allele was carried out by Southern blot, PCR, and sequencing. We were able to close down the region of the recombination event to an interval of 18 nucleotides, corresponding to the last 15 nucleotides of intron 2 and the first 3 nucleotides of exon 3 of the gene. These 18 nucleotides are identical between the gene and pseudogene making any further refinement impossible. An exhaustive list of published glucocerebrosidase complex alleles, describing their recombination points, is included for comparison.
In this autoradiographic study we have analysed the regional changes in the density of mu-opioid receptors produced by the chronic administration of sufentanil alone and after concurrent administration with nimodipine. mu-Opioid receptors in the central nervous system (CNS) of rats were labelled using 5 nM [3H]DAMGO. Sufentanil, a high-efficacy agonist, was administered for 7 days by chronic infusion (2 microg/h). Another group of animals received a simultaneous infusion of sufentanil (2 microg/h) and nimodipine (1 microg/h) for 7 days. These two drug regimes have been previously shown to induce tolerance and supersensitivity to the analgesic effect of the opioid, respectively. Our results clearly demonstrate that opioid tolerance is associated with a generalised down-regulation of mu-opioid binding sites throughout the brain and the spinal cord. Compared with the findings in tolerant animals, the CNS of animals supersensitive to sufentanil showed less down-regulation of mu-opioid receptors, to the extent that, particularly in brain areas related to nociception, such as the somatosensory cortex, central grey, raphe magnus nucleus and dorsal horn of the spinal cord, no down-regulation occurred. These neurochemical findings may contribute to the functional interaction between nimodipine and sufentanil that we have previously observed in analgesic studies.
The pathogenesis of cancer-associated hypercalcemia is not yet completely understood. This syndrome appears to be a consequence of the tumor production of humoral factors, mainly parathyroid hormone related protein (PTHrP). However, patients with humoral hypercalcemia of malignancy have features suggesting that factors other than PTHrP might play a role in this syndrome. We performed a case-control study in cancer patients with and without hypercalcemia. A total of 105 patients with a variety of tumors, 60 of them with hypercalcemia (corrected serum calcium over 2.6 mmol/l), and 45 without hypercalcemia. In a previous study, we demonstrated that plasma PTHrP was highly associated with hypercalcemia in these patients. In the present study, we measured the plasma levels of various bone cytokines: interleukin-1beta (IL-1beta), interleukin-6 (IL-6), transforming growth factor (TGF) alpha, and tumor necrosis factor (TNF) alpha, in these cancer patients. We also determined C-terminal type I procollagen (PICP) and C-terminal telopeptide of type I collagen (ICTP), bone formation and bone resorption markers, respectively, in serum in these patients. We found that these osteolytic cytokines do not increase in plasma by the presence of hypercalcemia. In fact, using a logistic regression analysis, a significant (P<0.02) association was found between the low plasma levels of IL-1beta and TGFalpha and hypercalcemia, independent of plasma PTHrP and the presence of bone metastasis, in these patients. No significant association between the plasma levels of IL-6 or TNFalpha and hypercalcemia was found in these cancer patients. Serum ICTP correlated (r=0.35; P=0.008) with hypercalcemia in these patients, but none of the cytokines studied in plasma correlated with either ICTP or PICP in these hypercalcemic patients. Our data indicate that the circulating levels of several bone cytokines are not enhanced by PTHrP in hypercalcemic cancer patients. The mechanism responsible for the association between the low plasma levels of some of these cytokines and hypercalcemia in these patients remains obscure. However, this finding does not rule out the possible local bone effects of these cytokines, contributing to hypercalcemia in cancer patients.
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In Antioquia and Chocó, traditional healers attend 60% of snakebites. With the aim to produce an inventory of the plants used by the healers to treat snakebites and to document the methods of preparation, administration, the dosage, number of patients treated throughout their years of practice with treatment results, 20 healers with experience in Bothrops, Porthidium and Bothriechis envenomations were interviewed between August, 1996 and November, 1998. They belong to nine black and three indigenous rural communities located near the towns of Bojayá, Vigía del Fuerte, Unguía (Atrato river valley), Nuquí and Bahía Solano (Pacific coast). Based on field interviews, 101 species of plants were identified as used to treat snakebites. The part used of each plant varies according to the species. Sixty plants are used in the form of drinks prepared by infusion, decoction or maceration; 78 as external baths on the affected extremity; 11 for steam application and 39 for poultices; the latter is used mainly when the bite is complicated by local necrosis. In mild and moderate envenomations, they generally use a mixture of three plants, while in severe cases they mix from five to 12, a handful of each one. Treatment is generally performed for 1-3 days, when the patient reacts positively. They reported to have treated 454 patients during their years of experience, 20 of them (4.4%) died. With the guidance of the healers, 77 species of plants were collected and photographed. These plants belong to 41 families, of which Piperaceae (13 species), Araceae (six species), Asteraceae (five species) and Gesneriaceae (three species) have the highest number of species.
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.
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.
Bulb mites of the genus Rhizoglyphus (Claparède) (Acari: Acaridae) have been identified as pests of many crops and ornamentals in storage, in the greenhouse, and in the field. The most important hosts are species in the family Liliaceae (e.g. Allium spp.), but bulb mites will often attack other important crops such as potatoes (Solanum sp.) and carrots (Daucus carota). Despite their economic importance and broad distribution, the systematics of the genus remains in a state of confusion and is in need of a comprehensive revision. In addition, the field biology and ecology of these mites is not well understood, and methods for sampling, monitoring, and loss assessment are limited. Management of bulb mites is complicated by their short generation time, high reproductive potential, broad food niche, interactions with other pests and pathogens, and unique adaptations for dispersal. Historically, control of these acarine pests has relied on the use of synthetic miticides and insecticides, but this option is now limited due to documented resistance and withdrawal of registration of some products. Alternative control strategies, including cultural and biological control, have shown limited success, but need to be further developed and implemented.