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Biomedical subjects

A Avila

Publications and source records attributed to A Avila.

At least 73 records · Page 4Linked to original sources
PubMed1993

Randomized comparative trial of three antivenoms in the treatment of envenoming by lance-headed vipers (Bothrops jararaca) in São Paulo, Brazil.

In São Paulo City, Brazil, 121 patients with moderately severe envenoming by Bothrops snakes (principally B. jararaca) were randomized for treatment with Brazilian polyspecific Bothrops antivenoms: Instituto Butantan (39 patients), Instituto Vital Brazil (41), Fundação Ezequiel Dias (FUNED) (41). The initial dose was four ampoules (40 ml) in 89 patients with less severe envenoming and eight ampoules (80 ml) in 32 patients with more severe envenoming. A second dose of four ampoules was required in 20 patients. Patients receiving the three antivenoms were comparable in all respects before treatment. There were no deaths. The majority showed rapid clinical improvement, resolution of local envenoming, cessation of bleeding and restoration of blood coagulability. No differences in the efficacy of the three antivenoms were revealed by clinical or laboratory observations, including measures of haematological, haemostatic and biochemical abnormalities. Twelve patients developed abscesses (Butantan 1, Vital Brazil 6, FUNED 5) and seven developed local necrosis (3,1,3). Of 88 patients followed up 20-30 days after the bite 33 (37.5%) still had symptoms or signs of local envenoming, especially swelling. Early (anaphylactic) reactions were unexpectedly frequent after all three antivenoms but were significantly more frequent with Butantan (87%) than with Vital Brazil (37%) or FUNED (56%) antivenoms (p < 0.001). A possible explanation was the higher total protein content and percentage immunoglobulin of Butantan antivenom. The doses of antivenom recommended in Brazil and used in this study may be unnecessarily high, resulting in an unacceptably high incidence of reactions. Results of the study should prompt a critical re-evaluation of antivenom production techniques and dosage recommendations in Brazil.

Adolescent↗
PubMed1991

Considerations for conducting epidemiologic case-control studies of cancer in developing countries.

The challenges involved in conducting epidemiologic studies of cancer in developing countries can be and often are unique. This article reports on our experience in performing a case-control study of invasive cervical cancer in four Latin American countries (Columbia, Costa Rica, Mexico, and Panama), the summary medical results of which have been published in a previous issue of this journal (1). The study involved a number of principal activities--mainly selecting, conducting interviews with, and obtaining appropriate biologic specimens from 759 cervical cancer patients, 1,467 matched female controls, and 689 male sex partners of monogamous female subjects. This presentation provides an overview of the planning and methods used to select the subjects, conduct the survey work, and obtain complete and effectively unbiased data. It also points out some of the important advantages and disadvantages of working in developing areas similar to those serving as locales for this study.

Case-Control Studies↗
PubMed1989

Diode laser in cervical myofascial pain: a double-blind study versus placebo.

We present a double-blind trial in which a pulsed infrared beam was compared with a placebo in the treatment of myofascial pain in the cervical region. The patients were submitted to 12 sessions on alternate days to a total energy dose of 5 J each. At each session, the four most painful muscular trigger points and five bilateral homometameric acupuncture points were irradiated. Those in the placebo group submitted to the same number of sessions following an identical procedure, the only difference being that the laser apparatus was nonoperational. Pain was monitored using the Italian version of the McGill pain questionnaire and the Scott-Huskisson visual analogue scale. The results show a pain attenuation in the treated group and a statistically significant difference between the two groups of patients, both at the end of therapy and at the 3-month follow-up examination.

Acupuncture Points↗
PubMed1988

Nephrotoxicity of high- and low-osmolality contrast media.

Nephrotoxicity of radio-opaque contrast media (CM) is generally believed to involve toxic injury of proximal tubular cells. Measurement of urinary tubular enzyme excretion has been advocated as a sensitive marker of such toxic injury. It has been claimed that the new low-osmolality or nonionic CM reduce the incidence of nephrotoxicity but this remains uncertain. We studied 23 patients with normal renal function undergoing coronary angiography; patients were randomized into three groups receiving either diatrizoate (1,800 mmol/kg H2O), ioxaglate (600 mmol/kg H2O) or iohexol (850 mmol/kg H2O). Urinary excretion of a panel of enzymes increased significantly in all groups by 20 h (p less than 0.05 to less than 0.005). Alanine aminopeptidase excretion at 20 h was greater after the administration of high osmolality ionic CM than with the others but all three CM produced a similar pattern of enzyme excretion. No significant change in glomerular filtration rate was found in any group so the significance of the enzymuria remains uncertain.

Adult↗
PubMed1987

Correlation of sinefungin susceptibility and drug-affinity for protein carboxymethyltransferase activity in American Leishmania species.

Among promastigotes of 22 different American Leishmania strains, a 5000-fold variation in sinefungin susceptibility was found, apparently independent of their taxonomic classification, although L. mexicana strains did tend to be more resistant than L. braziliensis. Protein carboxymethyltransferase (EC 2.1.1.24) and glycine N-methyltransferase (EC 2.1.1.20) activities were not substantially different in sinefungin-susceptible and -resistant American Leishmania strains. However, when [methyl-3H]methionine incorporation into total protein or gamma-glutamyl residues of leishmanial proteins was carried out in the presence or absence of sinefungin, protein carboxymethylating activity was significantly inhibited only in sinefungin-susceptible Leishmania strains. Furthermore, when protein carboxymethyltransferase activity was purified from several leishmanial strains to a state of electrophoretic homogeneity (sp. act. = 240 nmol h-1 (mg protein)-1), the enzyme from the resistant cells showed a higher inhibition constant (mean Ki 55 microM against 2 microM in susceptible cells) for sinefungin. This 28-times stronger affinity of the susceptible cell enzyme towards sinefungin despite normal protein carboxymethyltransferase specific activity seems to be a key element of the resistance mechanism of certain American Leishmania strains.

Adenosine↗
PubMed1987

Defective transport of pyrazolopyrimidine ribosides in insensitive Trypanosoma cruzi wild strains is a parasite-stage specific and reversible characteristic.

1. By using freshly isolated blood trypomastigotes of twelve T. cruzi wild type strains we have found eight strains sensitive to FoB and FoA, while four and one were FoA- and FoB-insensitive respectively to the drug-mediated growth inhibition. 2. This was not so for APPR, to which most strains were transitory insensitive except two which were clearly sensitive. 3. All these pyrazolopyrimidines blocked trypomastigote-amastigote transformation. 4. Incubation of pyrazolopyrimidine-insensitive wild strains with [3H]FoA, [3H]FoB and [14C]APPR respectively indicates that insensitive cells can only accumulate low concentrations of phosphorylated metabolites. 5. This is due to a defective or impaired pyrazolopyrimidine riboside transport system in the wild type insensitive cells, as we did not detect significant variations in the levels of the various nucleoside and nucleobase metabolism enzymes studied. 6. Additional experiments suggested that FoA and FoB are incorporated by different nucleoside transport systems, as Y and ES strains were FoA-insensitive but FoB-sensitive. 7. Epimastigotes of the same T. cruzi strains were highly sensitive to low concentrations of the three pyrazolopyrimidine ribosides studied. However, when this parasitic form was allowed to transform into trypomastigotes, these cells showed the same pyrazolopyrimidine sensitivity found before, suggesting that in T. cruzi pyrazolopyrimidine riboside-insensitivity is a parasite-stage specific and reversible biochemical characteristic.

Adenine↗
PubMed1987

Biological activity of analogs of guanine and guanosine against American Trypanosoma and Leishmania spp.

The growth inhibitory effects of six guanine and guanosine analogs, 3-deazaguanine (compound 1); 3-deazaguanosine (compound 2); 6-aminoallopurinol (compound 3); 9-beta-xylofuranosyl guanine (compound 4); a ribosylated derivative of compound 3, 6-aminopyrazolo(3,4-d)pyrimidin-4-one (compound 5); and 5-aminoformycin B (compound 6), were tested against some pathogenic members of the family of American Trypanosomatidae. Compounds 1 and 2 were highly active against Trypanosoma cruzi, Trypanosoma rangeli, and American Leishmania spp. in in vitro culture forms. Both compounds also showed antiprotozoal activity in T. cruzi-infected mice, with the optimal dose being about 30 mg/kg of body weight per day given as 10 consecutive doses. Compound 3 was the most active compound in vitro, inhibiting all of the American Trypanosomatidae culture forms tested. It was also highly inhibitory in mice that were acutely infected with T. cruzi, with the optimal dose being about 10 mg/kg of body weight per day. Ribosylation of compound 3 resulted in a derivative that showed decreased inhibitory activity on Trypanosomatidae multiplication. Compound 6 was highly inhibitory of in vitro multiplication of American Leishmania and T. rangeli but had no effect on T. cruzi epimastigotes and on mice that were acutely infected with T. cruzi. Compound 4 showed only a slight effect on T. cruzi epimastigotes.

Animals↗
PubMed1986

The use of brainstem auditory evoked potentials during posterior fossa surgery as a monitor of brainstem function.

Nine patients with unilateral ponto-cerebellar tumour, one with epidermoid, eight with acoustic neuroma had intraoperative monitoring of the brainstem auditory evoked potentials (BAEP) using bilateral scalp recording (Cz-A1 and Cz-A2) and binaural stimulation in order to monitor brainstem function during the surgery. Results were correlated with preoperative and postoperative BAEP findings. There was some intraoperative BAEP change in all the patients. Halothane anaesthesia caused bilateral wave V. prolongation in six patients. Lumbar drainage produced ipsilateral or bilateral wave V. prolongation in three of four patients in whom lumbar drainage was established. Opening the dura produced ipsilateral or bilateral wave V. depression or bilateral prolongation in four patients. Tumour dissection caused BAEP changes in all the patients: bilateral prolongation or depression in five patients, and ipsilateral prolongation and/or depression in six patients, three of them together with bilateral changes. The only patient who had no changes in wave I-IV. but in whom a big wave VI. appeared at the tumour side during removal, had epidermoid tumour. At the end of surgery there was some improvement in all patients, but in two the improvement was not striking: in one BAEP remained flat ipsilaterally, and in other, latency did not improve. All the patients had a good clinical recovery a few days later, but the control BAEP performed from the 3rd-7th postoperative day was not yet completely recovered in four patients. Intraoperative BAEP monitoring can be a useful technique to monitor brainstem function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Action of pyrazolopyrimidine derivatives on American Leishmania spp. promastigotes.

The capacity of 54 different pyrazolo-(3,4-d)- or -(4,3-d)-pyrimidine derivatives to inhibit American Leishmania promastigote multiplication was evaluated. Among pyrazolo-(3,4-d)-pyrimidines, eight derivatives showed leishmanistatic activity, 4-aminopyrazolo-(3,4-d)-pyrimidine (APP) being the most active, about eight-fold more than 4-hydroxy-pyrazolo-(3,4-d)-pyrimidine (HPP). 7-Hydroxy-3-beta-D-ribofuranosylpyrazolo-(4,3-d)-pyrimidine (FoB) was as active as 7-amino-3-beta-D-ribofuranosylpyrazolo-(4,3-d)-pyrimidine (FoA), a situation different to that found for pyrazolo-(3,4-d)-pyrimidines. Furthermore, different chemical modifications in formycin structure did not modify inhibitory effects. It can be concluded that regarding American Leishmania the chemical analogy to hypoxanthine or inosine of pyrazolo-(3,4-d)- and pyrazolo-(4,3-d)-pyrimidine, respectively, is not absolutely critical, as different modifications on the heterocyclic ring did not abolish the inhibitory activity of these compounds.

Animals↗
PubMed1986

The effects of a supratentorial mass lesion on brain-stem auditory evoked potentials and short latency somatosensory evoked potentials.

Nineteen patients with unilateral supratentorial mass lesion and without any evident clinical signs of transtentorial herniation were studied with Computed Tomography (CT), brain-stem evoked potentials (BAEPs) and central conduction time (CCT) of short latency somatosensory evoked potentials (SEPs). Sixteen had tumours, two had intracranial haematoma and one had chronic subdural haematoma. CT detected the initial signs of transtentorial herniation in every case. Preoperative I-V interpeak latency (IPL) was significantly (M + 2SD) prolonged in 26% of cases on the lesion side and in 21% of cases on the opposite side. The mean I-V IPL was significantly prolonged both on the lesion side and the opposite side (P less than 0.01, P less than 0.02, respectively). Suppression of Wave V (M-2SD) was seen only in two cases, however, the mean amplitude of Wave V was significantly decreased both on the lesion side and on the opposite side (P less than 0.001, P less than 0.01, respectively). CCT of SEPs was significantly (M + 2SD) prolonged in 33% of cases on the lesion side and in only 13% on the opposite side. The mean CCT was, however, significantly prolonged both on the lesion and on the opposite side (P less than 0.001, P less than 0.02, respectively). Postoperative I-V IPL was significantly prolonged in only 11% of cases while the mean I-V IPL was still significantly prolonged (P less than 0.01) and the mean amplitude of Wave V was still suppressed (P less than 0.001) on the lesion side.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Peripheral lymph flow in sheep with bacterial peritonitis: evidence for increased peripheral microvascular permeability accompanying systemic sepsis.

We studied the effects of systemic sepsis on peripheral microcirculatory fluid exchange by examining changes in flow (Qlymph) and lymph-to-plasma [L/P] total protein and albumin ratios from lymph draining, the efferent duct of a prefemoral lymph node in sheep, before and during surgically-induced peritonitis. After baseline study, peritonitis was produced by cecal ligation, perforation, and devascularization. By 24 hours blood cultures revealed a polymicrobial bacteremia. The hemodynamic response to the septic insult during the 72-hour study period was characterized by an increase in heart rate and an initial fall in stroke volume index; yet, the mean blood pressure remained unchanged from baseline levels throughout the study protocol. The intrapulmonary shunt fraction increased (p less than 0.05) by 48 hours, as did both the Qlymph (2.6 +/- 1.9 ml/hr to 6.8 +/- 4.6 ml/hr; p less than 0.05) and the calculated lymph albumin clearance (1.6 +/- 1.2 ml/hr to 3.1 +/- 1.7 ml/hr; p less than 0.05). Although the calculated serum to interstitial colloid osmotic pressure gradient fell (F = 4.37; p less than 0.04), both the [L/P] total protein and albumin ratios were unchanged from baseline throughout 72 hours of study. Further, [L/P] total protein ratios were unrelated to Qlymph (r = -0.20); as Qlymph (experimental/baseline) increased with sepsis, [L/P] total protein ratio (experimental/baseline) did not fall (r = +0.62). We therefore conclude that systemic sepsis, as represented by this model of bacterial peritonitis, results in increased peripheral microcirculatory fluid flux that is primarily a consequence of an increase in permeability of the peripheral microvascular exchanging membrane.

Animals↗
PubMed1985

Renal and cardiovascular response to nonhypotensive sepsis in a large animal model with peritonitis.

We studied the functional effects of intraperitoneal sepsis on systemic hemodynamics in general, and on renal function in particular, in sheep in whom bacterial peritonitis was induced by cecal perforation. In the first group of seven sheep (group 1) fluid was administered throughout the period of sepsis to maintain pulmonary capillary wedge pressure as close to presepsis values as possible. These sheep exhibited hemodynamic changes known to be associated with sepsis in man: increased cardiac output and decreased systemic vascular resistance. In a second group of seven sheep (group 2) fluid intake was restricted; compared with group 1, these sheep demonstrated a smaller increase in cardiac output that did not persist and that was associated with an increase in the systemic vascular resistance during the septic period. Plasma renin levels increased fivefold in group 2 but were unchanged in group 1. Serial renal biopsies during the septic period revealed that all sheep had evidence of tubular cell damage on electron microscopy: cell swelling, loss of the microvillous brush border, and cell necrosis. Both groups of sheep also demonstrated marked tubular proteinuria similar to that found in humans with generalized sepsis. Despite this, sheep in group 1 exhibited no functional renal changes: creatinine clearance levels rose slightly from control values, urine concentrating ability was unimpaired, and fractional excretion of sodium increased appropriately in response to a sodium load. In contrast, group 2 sheep exhibited a fall in creatinine clearance levels but fractional sodium excretion did not fall as would have been expected were renal function entirely normal. The results suggest that generalized "hyperdynamic" sepsis induces tubular cell damage and tubular proteinuria by an unknown mechanism. However, this does not necessarily produce renal impairment since the glomerular filtration rate does not fall unless volume contraction is also allowed to occur.

Animals↗
PubMed1984

Differences in allopurinol and 4-aminopyrazolo(3,4-d) pyrimidine metabolism in drug-sensitive and insensitive strains of Trypanosoma cruzi.

Most freshly isolated Trypanosoma cruzi blood trypomastigotes were insensitive to allopurinol (HPP) and 4-aminopyrazolo(3,4-d)pyrimidine (APP). Strains EP and Ya were, however, strongly inhibited by both drugs while strains DS and A-35 were HPP-insensitive but APP-sensitive. In contrast, epimastigotes resulting from one in vitro passage of all eleven T. cruzi strains were highly sensitive to both drugs. While hypoxanthine/guanine and adenine phosphoribosyltransferase and succino-AMP synthetase activities were similar in trypomastigotes of sensitive and insensitive T. cruzi strains, the uptake and metabolism of [14C]HPP and [14C]APP was significantly slower in T. cruzi trypomastigotes of insensitive strains than in sensitive strains. The results suggest the importance of drug uptake rates in determining the pyrazolopyrimidine sensitivity of different T. cruzi strains.

Adenine↗
PubMed1983

Trypanosoma cruzi: 4-aminopyrazolopyrimidine in the treatment of experimental Chagas' disease.

An allopurinol metabolite, 4-aminopyrazolopyrimidine, was tested on two different strains of mice (NMRI-IVIC and C57Bl/6J) that had been infected 4 days earlier with the virulent Ya strain of Trypanosoma cruzi. Low doses of 4-aminopyrazolopyrimidine (0.125-0.500 mg/kg body wt/day) for 10 days induced a significant reduction in parasitemia (direct counts and subinoculation experiments) and increased survival time (without any evidence of toxicity) compared with untreated animals. When tested in vitro, 4-aminopyrazolopyrimidine was sixfold more active than allopurinol as a trypanostatic drug. The low therapeutic doses of 4-aminopyrazolopyrimidine suggest that this drug may be useful in the treatment of acute Chagas' disease.

Adenine↗
PubMed1981

Differential metabolism of allopurinol and derivatives in Trypanosoma rangeli and T. cruzi culture forms.

We have compared the metabolism of allopurinol (4-hydroxypyrazolo (3,4-d)pyrimidine; HPP), by Trypanosoma rangeli, a non-pathogenic American trypanosome, and T. cruzi, the causative agent of Chagas' disease. Our results indicate that T. rangeli was unable to animate allopurinol mononucleotide to 4-aminopyrazolopyrimidine (APP) mononucleotide. Radioactivity was located in the RNA, but not the DNA, only of T. cruzi. Substrate specificity studies showed T. cruzi succino-AMP synthetase activity being 100-fold more active on HPP mononucleotide than the T. rangeli enzyme. These results possibly explain the fact that in conventional LIT medium T. rangeli growth was resistant to high concentrations of HPP. However the incubation of this hemoflagellate in an adenine-depleted LIT medium rendered it sensitive to low concentrations of APP, while remaining resistant to HPP. In contrast, and independently of the culture medium used, T. cruzi was extremely sensitive to both pyrazolopyrimidines.

Adenine↗