Identifying symptoms using the drawings of 4-7 year olds with cancer.

PURPOSE: Symptom burden in children with cancer who are less than 8 years old is not well understood. Our research focuses on identifying how to structure a self-report instrument for younger children. Our aim was to describe how children with cancer, aged 4-7 years, express their symptoms through drawings. METHODS: Children were asked to make drawings of a day when they were "feeling bad or not good". Content of 18 children's drawings was analyzed. RESULTS: Four themes were established: physical symptoms, emotions, location and miscellaneous. Most of the drawings illustrated specific symptoms important to this age group, while also facilitating our understanding of how children with cancer view their symptoms. CONCLUSION: Having children draw pictures may help initiate communication regarding how they feel, and develop rapport between the interviewer and children.

Self-report of symptoms in children with cancer younger than 8 years of age: a systematic review.

OBJECTIVE: The study's objective was to summarize the psychometric evaluation of self-report symptom instruments used in children with cancer younger than 8 years of age. METHODS: We conducted electronic searches of Ovid Medline, EMBASE, PsycInfo, Science Citation, Social Science Citation (Web of Science), and CINAHL. We included studies of children with cancer in which their self-report symptoms had been quantified and in which results were described for those younger than 8 years of age. The search was restricted to publications in English. Two reviewers screened studies and abstracted all data in duplicate. Descriptive analysis of reliability and validity was performed. RESULTS: Thirteen studies were included. Only one study recruited children <8 years alone. Most studies described reliability and validity in a wider age range cohort in which most children were older than 8 years of age. Of the eight studies that evaluated reliability within the younger age group, six raised concerns about poor internal consistency with Cronbach's alpha <0.7 in at least one dimension. Concerns about test re-test reliability and inter-rater reliability were also observed. None of the studies evaluated validity. CONCLUSIONS: We failed to demonstrate that currently available instruments to measure self-report symptoms are reliable or valid specifically for children with cancer younger than 8 years of age. Development of psychometrically robust instruments for younger children should be a priority.

Compartment syndrome after South American rattlesnake (Crotalus durissus terrificus) envenomation.

CONTEXT: In order to report the outcome of a patient who developed compartment syndrome after South American rattlesnake (Crotalus durissus terrificus) envenomation, confirmed by subfascial pressure measurement and magnetic resonance imaging (MRI). CASE DETAILS: A 63-year-old male was admitted 1 h after being bitten on the right elbow by a "large" snake, which was not brought for identification. Physical and laboratory features upon admission revealed two fang marks, local tense swelling, paresthesia, intense local pain, hypertension, coagulopathy, and CK = 1530 U/L (RV < 170 U/L). The case was initially treated with bothropic antivenom (80 mL, intravenously), with no improvement. Evolution within 13-14 h post-bite revealed generalized myalgia, muscle weakness, palpebral ptosis, and severe rhabdomyolysis (CK = 126,160 U/L) compatible with envenoming by C. d. terrificus. The patient was then treated with crotalic antivenom (200 mL, intravenously), fluid replacement, and urine alkalinization. Twenty-four-hour post-bite MRI showed marked muscular edema in the anterior compartment of the right forearm, with a high subfascial pressure (40 mmHg) being detected 1 h later. ELISA of a blood sample obtained upon admission, before antivenom infusion, revealed a high serum concentration of C. d. terrificus venom. No fasciotomy was performed and the patient was discharged seven days later without sequelae. CONCLUSION: Snakebite by C. d. terrificus with subfascial venom injection may lead to increased intracompartmental pressure.

Coagulopathy as the main systemic manifestation after envenoming by a juvenile South American rattlesnake (Crotalus durissus terrificus): case report.

CONTEXT: Rattlesnake bites in Brazil are generally caused by adult individuals, with most of the envenomed patients showing systemic manifestations that include varying degrees of neurotoxicity (acute myasthenia), rhabdomyolysis and coagulopathy, with only mild or no local manifestations. We report a case of envenoming by a juvenile South American rattlesnake (Crotalus durissus terrificus) that involved coagulopathy as the main systemic manifestation. CASE DETAILS: A 19-year-old male was admitted to our Emergency Department with coagulopathy (incoagulable PT, APTT and INR), no remarkable local manifestations and no signs/symptoms of myasthenia or rhabdomyolysis (serum CK, LDH, ALT and AST within reference levels) 5 days after being bitten by a small snake that was described as a rattlesnake but was not brought for identification at admission. The patient had already been treated in another Emergency Department with i.v. bothropic antivenom (AV) 1 h and 4 days post-bite. Based on the possibility of an unusual rattlesnake bite, crotalic AV was administered i.v., which improved the coagulation (9 h post-CroAV, INR = 2.11; 36 h post-CroAV, INR = 1.42). During hospitalization, relatives brought the snake that caused the bite, which was identified as a 38-cm long C. d. terrificus. DISCUSSION: Little is known about the clinical manifestations after bites by juvenile C. d. terrificus. This case shows that systemic envenoming by juvenile C. d. terrificus may result in coagulopathy as the main systemic manifestation, without neuromyotoxic features normally associated with bites by adult specimens. Despite the delayed administration, crotalic AV was effective in improving the blood coagulation.

Neuromuscular activity of BaTX, a presynaptic basic PLA2 isolated from Bothrops alternatus snake venom.

We have previously isolated a Lys49 phospholipase A(2) homolog (BaTX) from Bothrops alternatus snake venom using a combination of molecular exclusion chromatography and reverse phase HPLC and shown its ability to cause neuromuscular blockade. In this work, we describe a one-step procedure for the purification of this toxin and provide further details of its neuromuscular activity. The toxin was purified by reverse phase HPLC and its purity and molecular mass were confirmed by SDS-PAGE, MALDI-TOF mass spectrometry, amino acid analysis and N-terminal sequencing. BaTX (0.007-1.4 microM) produced time-dependent, irreversible neuromuscular blockade in isolated mouse phrenic nerve-diaphragm and chick biventer cervicis preparations (time to 50% blockade with 0.35 microM toxin: 58+/-4 and 24+/-1 min, respectively; n=3-8; mean+/-S.E.) without significantly affecting the response to direct muscle stimulation. In chick preparations, contractures to exogenous acetylcholine (55 and 110 microM) or KCl (13.4 mM) were unaltered after complete blockade by all toxin concentrations. These results, which strongly suggested a presynaptic mechanism of action for this toxin, were reinforced by (1) the inability of BaTX to interfere with the carbachol-induced depolarization of the resting membrane, (2) a significant decrease in the frequency and amplitude of miniature end-plate potentials, and (3) a significant reduction (59+/-4%, n=12) in the quantal content of the end-plate potentials after a 60 min incubation with the toxin (1.4 microM). In addition, a decrease in the organ bath temperature from 37 degrees C to 24 degrees C and/or the replacement of calcium with strontium prevented the neuromuscular blockade, indicating a temperature-dependent effect possibly mediated by enzymatic activity.

In vitro hemolytic activity of Bothrops lanceolatus (fer-de-lance) venom

Bothrops lanceolatus venom contains a variety of enzymatic and biological activities. The present work investigated the hemolytic activity of this venom and its phospholipase A2 (PLA2). Bothrops lanceolatus venom (6.7 µg/mL) caused indirect hemolysis of cow, horse, rat and sheep erythrocytes, with horse erythrocytes being the most sensitive; no direct hemolysis was observed. Hemolysis in sheep erythrocytes was concentration-dependent (5-11.7 µg/mL) and markedly attenuated by heating the venom for 30 minutes at ≥ 40°C and by the PLA2 inhibitor p-bromophenacyl bromide. An acidic PLA2 (5 µg/mL) purified from B. lanceolatus venom also caused hemolysis. This PLA2 showed immunoprecipitin lines with antivenom against B. lanceolatus, which suggests that the enzymatic and hemolytic activities of this enzyme may be neutralized during antivenom therapy. These results indicate that B. lanceolatus venom and its PLA2 can cause hemolysis in vitro.(AU)

Acute hepatotoxicity of Crotalus durissus terrificus (South American rattlesnake) venom in rats

Venom of the South American rattlesnake, Crotalus durissus terrificus (Cdt), presents myotoxic and neurotoxic outcomes, but reports on its effects on the liver are scarce. This study examined the hepatotoxicity resulting from Cdt venom administration (100, 200 and 300 miug/kg) in male Wistar rats. Animais were studies at 3, 9 and 12 hours after venom injection. The hepatotoxicity was assessed through serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), bilirrubin and also by histopathological evaluation. All the different concentrations of Cdt venom resulted in increased levels of hepatic enzymes, when compared with the control group, except for the 100 miug/kg dose, which presented normal levels at 9 and 12 hours after venom administration. Bilirrubin levels remained unchanged by Cdt venom. Histological analysis revealed endothelial damage, inflammatory cell infiltration, as well as sinusoidal and portal congestion. Based on these observations, we may conclude that Cdt venom causes dose- and time-dependent hepatic damage in rats, characterized by elevated hepatic enzyme levels and histological alterations

Bothrops snakebite on the head: case report and review of the literature.

A previously healthy, 21-year-old female was admitted 5 h after being bitten in the occipital region by a pitviper presumed to be Bothrops jararaca. Physical examination revealed marked cranial and facial oedema extending to the neck and dorsum, bilateral eyelid ecchymosis, and local conjunctival and gingival bleeding. The patient was alert and complained of mild, local pain and nausea. There were no signs of neurological involvement. The main laboratory findings on admission included incoagulable blood, a platelet count of 4000/microl, and an ELISA-estimated serum venom concentration of 62.6 ng/ml. Sequential serum creatinine, urea nitrogen, sodium and potassium concentrations were normal. The case was classified as severe and, after the intravenous administration of ranitidine, chlorpheniramine and hydrocortisone, the intravenous infusion of 12 vials of undiluted bothropic equine antivenom [F(ab)(2); 10 ml/vial] was initiated. The antivenom infusion was halted after 10 vials because the patient developed a severe early reaction, although this was successfully treated with subcutaneous adrenaline and intravenous hydrocortisone. Platelet replacement (seven units) was performed and 24 h after the antivenom infusion, normal results in blood-coagulation tests and an increase in the platelet count (to 100,000/microl) were observed. No circulating venom was detected in blood samples collected 6, 12, 24 or 48 h post-admission. The patient was discharged after 4 days, with clinical improvement and no signs of local infection, and subsequent follow-up revealed no sequelae.

Binding of netropsin to several DNA constructs: evidence for at least two different 1:1 complexes formed from an -AATT-containing ds-DNA construct and a single minor groove binding ligand.

Isothermal titration calorimetry, ITC, has been used to determine the thermodynamics (DeltaG, DeltaH, and -TDeltaS) for binding netropsin to a number of DNA constructs. The DNA constructs included: six different 20-22mer hairpin forming sequences and an 8-mer DNA forming a duplex dimer. All DNA constructs had a single -AT-rich netropsin binding with one of the following sequences, (A(2)T(2))(2), (ATAT)(2), or (AAAA/TTTT). Binding energetics are less dependent on site sequence than on changes in the neighboring single stranded DNA (hairpin loop size and tail length). All of the 1:1 complexes exhibit an enthalpy change that is dependent on the fractional saturation of the binding site. Later binding ligands interact with a significantly more favorable enthalpy change (partial differential DeltaH(1-2) from 2 to 6 kcal/mol) and a significantly less favorable entropy change (partial differential (-TDeltaS(1-2))) from -4 to -9 kcal/mol). The ITC data could only be fit within expected experimental error by use of a thermodynamic model that includes two independent binding processes with a combined stoichiometry of 1 mol of ligand per 1 mol of oligonucleotide. Based on the biophysical evidence reported here, including theoretical calculations for the energetics of "trapping" or structuring of a single water molecule and molecular docking computations, it is proposed that there are two modes by which flexible ligands can bind in the minor groove of duplex DNA. The higher affinity binding mode is for netropsin to lay along the floor of the minor groove in a bent conformation and exclude all water from the groove. The slightly weaker binding mode is for the netropsin molecule to have a slightly more linear conformation and for the required curvature to be the result of a water molecule that bridges between the floor of the minor groove and two of the amidino nitrogens located at one end of the bound netropsin molecule.

Determination of the amino acid sequence of a new phospholipase A(2) (MIDCA1) isolated from Micrurus dumerilii carinicauda venom.

A new Phospholipase A(2) (PLA(2)) from Micrurus dumerilii carinicauda venom was isolated and its primary structure determined. This new PLA(2) showed a low enzymatic activity when compared with other PLA(2)s and it is moderately basic with an isoelectric point of 8.0. Its amino acid sequence showed the presence of 120 amino acid residues and its sequence was: NLIQFLNMIQCTTPGREPLVAFANYGCYCGRGGSGTPVDELDRCCQVHDNCYDTAKKVFGCSPYFTMYSYDCSEGKLTCKDNNTKCKAAVCNCDRTAALCFAKAPYNDKNYKIDLTKRCQ. The structural model of MIDCA1, when compared with other strong neurotoxic PLA(2)s, such as Naja naja, showed significant differences in the beta-wing and neurotoxic sites, despite the high level of amino acid sequence similarity. These observations indicate a dissociation between the biological and catalytic activity of this new PLA(2), supporting the view that other regions of the protein are involved in the biological effects.