Publications by authors named "Isabel Gomila"

26 Publications

  • Page 1 of 1

Cardiac arrest following unsuspected self-poisoning with doxylamine.

Ther Drug Monit 2022 Jan 11. Epub 2022 Jan 11.

Clinical Toxicology Unit, Clinical Analysis Department. Hospital Universitari Son Llàtzer. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Intensive Care Department. Hospital Universitari Son Llàtzer. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Intensive Care Department. Hospital Universitari Son Llàtzer. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Intensive Care Department. Hospital Universitari Son Llàtzer. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Cardiology Department. Hospital Universitari Son Llàtzer. Department of Medicine, Faculty of Medicine, University of the Balearic Islands. Research Institute of Health Sciences (IdISBa). Palma de Mallorca, Spain. Institute of Legal Medicine of the Balearic Islands. Ministry of Justice. Department of Medicine, Faculty of Medicine, University of the Balearic Islands. Palma de Mallorca, Spain. Institute of Legal Medicine of the Balearic Islands. Ministry of Justice. Department of Medicine, Faculty of Medicine, University of the Balearic Islands. Palma de Mallorca, Spain.

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http://dx.doi.org/10.1097/FTD.0000000000000960DOI Listing
January 2022

Clinical features and risk factors associated with prenatal exposure to drugs of abuse.

An Pediatr (Engl Ed) 2021 Nov 9;95(5):307-320. Epub 2021 Oct 9.

Servicio de Análisis Clínicos, Unidad de Toxicología Clínica, Hospital Universitario Son Espases, Palma de Mallorca, Spain; Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma de Mallorca, Spain. Electronic address:

Introduction: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management.

Objectives: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit.

Methods: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed.

Results: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)).

Conclusions: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.
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http://dx.doi.org/10.1016/j.anpede.2020.08.013DOI Listing
November 2021

Role of Neonatal Biomarkers of Exposure to Psychoactive Substances to Identify Maternal Socio-Demographic Determinants.

Biology (Basel) 2021 Apr 4;10(4). Epub 2021 Apr 4.

Clinical Toxicology Research Group, Balearic Islands Health Research Institute (IdISBa), Valldemossa Road, 79, 07120 Palma de Mallorca, Spain.

Background: The accurate assessment of fetal exposure to psychoactive substances provides the basis for appropriate clinical care of neonates. The objective of this study was to identify maternal socio-demographic profiles and risk factors for prenatal exposure to drugs of abuse by measuring biomarkers in neonatal matrices.

Methods: A prospective, observational cohort study was completed. Biomarkers of fetal exposure were measured in meconium samples. The mothers were interviewed using a questionnaire. Univariate and multivariate logistic regression analyses were performed.

Results: A total of 372 mothers were included, 49 (13.2%) testing positive for psychoactive substances use: 24 (49.0%) for cannabis, 11 (22.5%) for ethyl glucuronide, six (12.2%) for cocaine, and in eight (16.3%) more than one psychoactive substance. Mothers who consumed any psychoactive substance (29.7 ± 6.6 years) or cannabis (27.0 ± 5.7 years) were younger than non-users (32.8 ± 6.2 years, < 0.05). Cocaine (50.0% vs. 96.9%, < 0.05) and polydrug users (37.5% vs. 96.9%, < 0.05) showed a lower levels of pregnancy care. Previous abortions were associated with the use of two or more psychoactive substances (87.5% vs. 37.8%, < 0.05). Single-mother families (14.3% vs. 2.5%, < 0.05) and mothers with primary level education (75.5% vs. 55.1%, < 0.05) presented a higher consumption of psychoactive substances. Independent risk factors that are associated with prenatal exposure include: maternal age < 24 years (odds ratio: 2.56; 95% CI: 1.12-5.87), lack of pregnancy care (odds ratio: 7.27; 95%CI: 2.51-21.02), single-mother families (odds ratio: 4.98; 95%CI: 1.37-8.13), and active tobacco smoking (odds ratio: 8.13; 95%CI: 4.03-16.43).

Conclusions: These results will allow us to develop several risk-based drug screening approaches to improve the early detection of exposed neonates.
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http://dx.doi.org/10.3390/biology10040296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067052PMC
April 2021

[Clinical features and risk factors associated with prenatal exposure to drugs of abuse].

An Pediatr (Engl Ed) 2020 Oct 8. Epub 2020 Oct 8.

Servicio de Análisis Clínicos, Unidad de Toxicología Clínica, Hospital Universitario Son Espases, Palma de Mallorca, España; Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Palma de Mallorca, España. Electronic address:

Introduction: Early identification of neonates exposed to drugs of abuse during pregnancy allows a more precise clinical management.

Objectives: To describe the clinical characteristics and to identify risk factors associated with the early detection of neonates exposed to drugs of abuse in a Neonatal Intermediate and Intensive Care Unit.

Methods: Prospective observational study of neonates with and without clinical suspicion of prenatal exposure to drugs of abuse. Meconium was analyzed using standard chromatographic techniques. Univariate and multivariate statistical analyzes were performed.

Results: 372 neonates were included. Exposure to drugs of abuse was detected in 49 (13.2%) cases: in 41 (83.7%) one drug and in 8 (16.3%) more than one. Somatometry at birth revealed: a) lower length percentile in those exposed to some drug, more than one and cannabis; b) lower weight percentile in those exposed to cannabis and of these compared to those exposed to alcohol. In neonates older than 34 pregnancy weeks (PW): a) lower length percentile in those exposed to any substance; b) lower percentile of length and weight in exposed to more than one. The most clinically relevant independent risk factors useful to detect cases of prenatal exposure to drugs of abuse were (Odds ratio (95% CI)): reason for admission other than prematurity (5.52 (2.55-1.93)), length percentile less than 33 (1.95 (1.05-3.60) and 2.14 (1.04-3.40) in older than 34 PW) and social dystocia/uncontrolled pregnancy in older than 34 PW (4.47 (1.03-19.29)).

Conclusions: There are somatometric alterations and risk factors that can help in the early detection of neonates exposed to drugs of abuse. The somatometric alterations identified can be useful to extend the differential diagnosis of these alterations and to study their causes.
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http://dx.doi.org/10.1016/j.anpedi.2020.08.003DOI Listing
October 2020

Diminished Consciousness in a Woman Following an Unsuspected Scopolamine Overdose.

J Anal Toxicol 2021 Jul;45(6):e7-e14

Clinical Toxicology Unit, Clinical Analysis Department, Hospital Universitari Son Espases. Research Institute of Health Sciences (IdISBa), Valldemossa road 79, 07120 Palma de Mallorca, Spain.

Scopolamine is used clinically, but it is also used as a recreational drug and as an incapacitating drug, in sexual crimes and robberies. In this paper, the authors report the case of a woman with a diminished consciousness following an unsuspected overdose with scopolamine and review published articles on scopolamine poisoning that included concentrations in biological samples. Scopolamine was identified in the patient's serum and urine samples collected 1 h post-admission to intensive care unit at concentrations of 8.4 ng/mL and 62,560 ng/mL (169,539 ng/mg creatinine), respectively. In non-fatal cases, the median [interquartile range] of serum scopolamine levels was 1.9 [2.1] ng/mL. The serum concentration found in our case would explain the abrupt clinical presentation suffered by the patient. Scopolamine in urine could be detected up to 48 h after admission. This report illustrates that broad toxicology screening, including scopolamine, should be considered when patients with diminished consciousness are attended after ruling out infection or cerebrovascular disease. This can play an important role in identifying this potentially life-threatening etiology.
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http://dx.doi.org/10.1093/jat/bkaa135DOI Listing
July 2021

Detectability of Dissociative Psychoactive Substances in Urine by Five Commercial Phencyclidine Immunoassays.

J Anal Toxicol 2019 Jul;43(6):497-503

Hospital Universitari Son Espases, Clinical Toxicology Unit, Clinical Analysis Department, Research Institute of Health Sciences (IdIsBa), Palma de Mallorca, Spain.

Methoxetamine (MXE) and the arylcyclohexylamines 3-methoxy-PCP (3-MeO-PCP) and 4-methoxy-PCP (4-MeO-PCP) are substituted analogs of the dissociative psychoactive substances ketamine and phencyclidine (PCP), respectively. They have emerged on the new psychoactive substances (NPS) market as legal alternatives to these classically banned dissociatives. Little data has been published regarding the cross-reactivity of these NPS in PCP immunoassays (IAs). The aim of this work was to explore the possibilities of detecting 3-MeO-PCP, 4-MeO-PCP, MXE and ketamine in commercial IAs for PCP. The cross-reactivity study was performed in five different PCP IAs using urine-free, spiked samples and urine samples obtained from two 3-MeO-PCP overdose cases. 3-MeO-PCP and 4-MeO-PCP showed cross-reactivity (ranging from 1-143%) in all PCP IAs evaluated. MXE only showed very weak cross-reactivity (ranged from 0.04 to 0.25%) and ketamine was not detected in any PCP IA evaluated. Urine samples from the two overdose cases were positive for PCP in all IAs evaluated. The commercial PCP IAs evaluated exhibited utility as rapid, preliminary screening techniques for 3-MeO-PCP and 4-MeO-PCP, but not for ketamine. The low reactivity of MXE limits its detectability in the PCP IAs evaluated.
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http://dx.doi.org/10.1093/jat/bkz026DOI Listing
July 2019

2,4-Diamino-N10-methylpteroic acid (DAMPA) crystalluria in a patient with osteosarcoma treated with carboxypeptidase-G2 rescue after high-dose methotrexate-induced nephrotoxicity.

Clin Chim Acta 2018 Dec 8;487:1-5. Epub 2018 Sep 8.

Clinical Analysis Department, Hospital Universitari Son Espases, Research Institute of Health Sciences (IdISBa), Ctra. de Valldemossa, 79, 07120 Palma de Mallorca, Spain. Electronic address:

Background: High-dose methotrexate (HDMTX) therapy is a key component of many chemotherapy protocols. However, some patients develop HDMTX-induced nephrotoxicity. Carboxypeptidase-G2 (CPDG2) hydrolyses MTX into 2,4-diamino-N10-methylpteroic acid (DAMPA) and glutamic acid, and is used as a rescue agent in patients with nephrotoxicity and delayed elimination. Despite the frequency of HDMTX-induced renal injury, crystalluria is uncommon. Furthermore, crystals are rarely identified by conventional chemical methods.

Objective: To determine the composition of crystalluria in a patient with osteosarcoma who was treated with CPDG2.

Methods: Crystalluria was evaluated by optical microscopy, and chemical identification was performed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and Orbitrap™ high-resolution mass spectrometry (HRMS).

Results: The HRMS spectra of the patient's urine sediment showed a main peak at m/z 326.13, corresponding to the molecular mass of DAMPA [(CHON) + H]. The FT-IR spectral patterns of the sediment and DAMPA were not identical. SEM was unable to identify the crystal.

Conclusion: DAMPA crystalluria was identified by Orbitrap™ HRMS in a patient treated with CPDG2 after HDMTX nephrotoxicity. This case reinforces the need to implement adequate measures to prevent nephrotoxicity. In cases of HDMTX-induced nephrotoxicity, urine sediment analysis should be requested.
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http://dx.doi.org/10.1016/j.cca.2018.09.006DOI Listing
December 2018

Value of glycolic acid analysis in ethylene glycol poisoning: A clinical case report and systematic review of the literature.

Forensic Sci Int 2018 Sep 17;290:e9-e14. Epub 2018 Jul 17.

Clinical Toxicology Unit, Clinical Analysis Department, Hospital Universitari Son Espases, Research Institute of Health Sciences (IdISBa), Ctra. de Valldemossa, 79, 07120 Palma de Mallorca, Spain. Electronic address:

Objective: To evaluate the clinical utility of glycolic acid (GA) determination in the diagnosis and prognosis of ethylene glycol (EG) intoxications.

Method: Systematic review of serum and/or urine GA concentrations available in the literature in cases of EG poisoning. Present a clinical case in which the determination of the GA was decisive.

Results: In total, 137 patients were included. Serum GA concentrations (but not EG) of patients who survive are different from those who die. The optimal cut-off of serum GA to predict mortality was 990.5mg/L (sensitivity 85.2%, specificity 54.3%) with an Odds Ratio of 6.838 (2.868-16.302). In our clinical case, serum EG was negative; however, urine GA was positive (1230.7mg/L).

Conclusions: In all suspected cases of EG poisoning, it is advisable to carry out the simultaneous analysis of EG and GA.
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http://dx.doi.org/10.1016/j.forsciint.2018.07.007DOI Listing
September 2018

Building Bridges between Clinical and Forensic Toxicology Laboratories.

Curr Pharm Biotechnol 2018 ;19(2):99-112

Clinical Analysis Department, Hospital Universitari Son Llatzer, Balearic Islands Health Research Institute (IdISBa), Palma de Mallorca, Spain.

Background: Clinical and forensic toxicology can be defined as two disciplines involving the detection, identification and measurement of xenobiotics in biological and non-biological samples to assist in the diagnosis, treatment, prognosis and prevention of poisonings and to disclose causes and contributory causes of fatal intoxications, respectively.

Objective: This article explores the close connections between clinical and forensic toxicology in overlapping areas of interest.

Methods: An update has been carried out of the following seven areas of interest in analytical toxicology: doping control, Sudden Cardiac Death (SCD), brain death, Sudden Infant Death Syndrome (SIDS) and Munchausen Syndrome by Proxy (MSBP), prenatal exposure to drugs and Fetal Alcohol Syndrome (FAS), Drug-Facilitated Crimes (DFC) and intoxications by new psychoactive substances (NPS).

Results: While issues such as SCD, SIDS or doping control are investigated mainly in forensic laboratories, others such as prenatal exposure to drugs or FAS are mainly treated in clinical laboratories. On the other hand, areas such MSBP, DFC or the intoxications by NPS are of interest in both laboratories. Some of these topics are initially treated in hospital emergency departments, involving clinical laboratories and sometimes lately derived to forensic laboratories. Conversely, cases with initial medicallegal implications and fatalities are directly handled by forensic toxicology, but may trigger further studies in the clinical setting.

Conclusion: Many areas of common interest between clinical and forensic laboratories are building bridges between them. The increasing relationships are improving the growth, the reliability and the robustness of both kinds of laboratories.
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http://dx.doi.org/10.2174/1389201019666180509163603DOI Listing
October 2018

Orbitrap™ high-resolution mass spectrometry for the identification of amoxicillin crystalluria.

Clin Chem Lab Med 2018 10;56(11):268-271

Laboratory of Renal Lithiasis Research, University Institute of Health Sciences Research (IUNICS-IdISBa), University of Balearic Islands, Palma de Mallorca, Spain.

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http://dx.doi.org/10.1515/cclm-2018-0163DOI Listing
October 2018

Quantification of Methamphetamine «Shabu» in Biological Matrices to Detect Prenatal Exposure: A Case Report and a Literature Review.

Curr Pharm Biotechnol 2018 ;19(2):163-174

Drug Testing Consultants, #801 265 Russell Hill Road, Toronto, ON, M4V2T3, Canada.

Background: Methamphetamine misuse represents an increasing global public health problem. Its consumption during pregnancy becomes a relevant issue, since it has clinical consequences for the child's health and the pregnant woman. Despite this, there are only few data in the literature that include analytical results in the matrices used to detect prenatal exposure.

Objectives: 1) Present a case report of prenatal methamphetamine exposure with toxicological analytical confirmation in biological matrices; and 2) Perform a compilation of prenatal methamphetamine exposure studies and case reports which include toxicological analytical results.

Methods: Prenatal methamphetamine exposure was confirmed using a traditional "screen with reflex" approach. Methamphetamine and amphetamine were quantified in urine, meconium and hair samples of the neonate and mother by gas chromatography-mass spectrometry. Also, a detailed revision of the existent literature that provides information on the analytical toxicology results has been included.

Results: In the neonatal biological matrices test results of methamphetamine/amphetamine were: urine 2,966.43/1,638.71 ng/mL, meconium 1,450/<0.1 ng/g and hair 36.54/9.66 ng/mg. In the maternal biological matrices, test results were: urine 13,393.89/3,074.95 ng/mL and hair 11.29/3.37 ng/mg (0-3 cm), 4.68/2.58 (3-6 cm), 6.43/3.13 ng/mg (6-9 cm) and 4.72/2.49 ng/mg (9-12 cm). These results confirm a recent and continued regular substance use throughout pregnancy including delivery.

Conclusion: The data provided will be useful for clinical purposes to improve the diagnostic and follow- up of acute and chronic intoxications. Additionally, results will be used to support interpretations in the field of forensic and legal medicine.
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http://dx.doi.org/10.2174/1389201019666180427111735DOI Listing
October 2018

The importance of biomarkers of fetal exposure to alcohol and psychotropic drugs in early diagnosis: A case report.

Drug Test Anal 2018 May 7;10(5):895-898. Epub 2018 Feb 7.

Clinical Toxicology Unit, Clinical Analysis Department, Hospital Universitari Son Espases, Research Institute of Health Sciences (IdISBa), Palma de Mallorca, Spain.

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http://dx.doi.org/10.1002/dta.2360DOI Listing
May 2018

Cross-Reactivity of Pantoprazole with Three Commercial Cannabinoids Immunoassays in Urine.

J Anal Toxicol 2017 Nov;41(9):760-764

Division of Emergency Laboratory, Hospital Universitari de Bellvitge, Barcelona, Spain.

Pantoprazole is a frequently prescribed proton pump inhibitor (PPI) commonly utilized in the management of gastrointestinal symptoms. Few substances have proved to cause a false-positive cannabinoid urine screen. However, a case of false-positive urine cannabinoid screen in a patient who received a pantoprazole dose has been recently published. The purpose of this study was to determine the potential cross-reactivity of pantoprazole in the cannabinoid immunoassays: Alere Triage® TOX Drug Screen, KIMS® Cannabinoids II and DRI® Cannabinoids Assay. Drug-free urine to which pantoprazole was added up to 12,000 μg/mL produced negative results in the DRI® Cannabinoids and KIMS® Cannabinoids II. Alere Triage® TOX Drug Screen assay gave positive results at pantoprazole concentrations higher than 1,000 μg/mL. Urine samples from 8 pediatric patients were collected at the beginning of their pantoprazole treatment. Alere Triage® TOX Drug Screen assay produced positive test results in all patient samples and KIMS® Cannabinoids II immunoassay produced positive test results in one patient sample. None patient sample gave a false-positive result when analyzed by the DRI® Cannabinoids Assay. Our findings demonstrate that some cannabinoids immunoassays are susceptible to cross-reaction errors resulting from the presence in urine of pantoprazole and the resulting metabolism of the parent drug. Clinicians should be aware of the possibility of false-positive results for cannabinoids after a pantoprazole treatment.
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http://dx.doi.org/10.1093/jat/bkx047DOI Listing
November 2017

Cross-reactivity of selected benzofurans with commercial amphetamine and ecstasy immunoassays in urine.

Bioanalysis 2017 Nov 4;9(22):1771-1785. Epub 2017 Oct 4.

Balearic Islands Health Research Institute (IdISBa), 07120 Palma de Mallorca, Spain.

Aim: The aim of this study was to perform a cross-reactivity investigation of six benzofurans with immunoassays (IAs) screening tests for amphetamines and ecstasy in urine samples.

Methods: The following benzofuranes were investigated: 5-(2-Methylaminopropyl)Benzofuran (5-MAPB), 5-(2-methylaminopropyl)-2,3-dihydrobenzofuran (5-MAPDB), 5-(2-Aminopropyl)-Benzofuran (5-APB), 5-(2-Aminopropyl)-2,3-dihydrobenzofuran (5-APDB), 5-(2-Ethylaminopropyl)Benzofuran (5-EAPB) and 5-(2-Aminoethyl)-2,3-dihydrobenzofuran (5-AEDB). The study was performed with urine-free spiked samples and authentic urine samples using eight different IAs for amphetamines and ecstasy. Results: All evaluated benzofurans showed cross-reactivity in some of the IAs tested, except for 5-AEDB. Urine samples of an intoxication case involving 5-MAPB, 5-APB and 5-EAPB were also positives in the IAs tested.

Conclusion: There is an important variability in the cross-reactivity of the IAs for amphetamine and ecstasy caused by benzofurans depending on the immunoassay employed and the tested compounds.
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http://dx.doi.org/10.4155/bio-2017-0191DOI Listing
November 2017

Pharmacology and Literature Review Based on Related Death and Non-Fatal Case Reports of the Benzofurans and Benzodifurans Designer Drugs.

Curr Pharm Des 2017 ;23(36):5523-5529

Clinical Toxicology Unit, Clinical Analysis Department. Hospital Universitari Son Espases. Research Institute of Health Sciences (IdISPa). Palma de Mallorca, Spain.

Background: Benzofurans and benzodifurans are two groups of psychoactive substances that had originally been synthesized for research purpose. Benzofurans' structure is quite similar to the known recreational drug 3,4-methylenedioxymethamphetamine together with its active metabolite 3,4-methylenedioxyamphetamine. Benzodifurans are closely related to phenethylamines, but have more hallucinogens effects and much longer duration of action. This study aims to review the accessible evidence-based literature on benzofurans and benzodifurans pharmacology and toxicology.

Methods: A literature search on benzofurans and benzodifurans has been conducted using PubMed. We reviewed articles up to February 2017 and also included data from various governmental websites and discussion groups.

Results: This review describes the emergent literature that illustrates the chemical composition of these drugs, patterns of use, pharmacology, toxicology, desired and clinical effects, and treatments of patients. It also provides a compilation of case reports.

Conclusion: The knowledge regarding usage prevalence, pharmacokinetic and pharmacodynamic profiles, acute toxic effects, the effects desired on patients and drug related mortality attributed to these drugs is still limited. Nowadays, there are no specific guidelines available to treat benzofurans or dibenzofurans intoxications. For that reason, clinical effects should be the base of treatment. Backing exposures analytically confirmed in clinical and forensic cases and reported clinical effects need to be combined with these compounds while monitoring its prevalence.
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http://dx.doi.org/10.2174/1381612823666170714155140DOI Listing
June 2019

Intoxication caused by new psychostimulants: analytical methods to disclose acute and chronic use of benzofurans and ethylphenidate.

Int J Legal Med 2017 Nov 15;131(6):1543-1553. Epub 2017 Jul 15.

Unit of Forensic Toxicology (UoFT), Department of Anatomical, Histological, Forensic and Orthopedic Sciences, Sapienza University of Rome, Viale Regina Elena, 336, Rome, Italy.

The acute and chronic toxicity of several new psychoactive substances (NPS) is unknown, and only little information is available on the pharmacology and toxicology, toxicokinetics, and detectability in body samples of such new compounds. We here propose analytical methods to disclose acute and chronic use of two types of new psychostimulants: benzofurans and ethylphenidate and we applied them to a real case of a subject attending Emergency Department with signs of acute intoxication due to psychotropic drug(s). After a urinary immunoassay screening which gave a positivity to amphetamines, general unknown gas chromatography-mass spectrometry (GC-MS) urine analysis identified 5-(2-methylaminopropyl)benzofuran (5-MAPB), 5-(2-aminopropyl)benzofuran (5-APB), 5-(2-ethylaminopropyl)benzofuran (5-EAPB), ethylphenidate, and ritalinic acid. All these substances were confirmed and quantified not only in urine but also in serum samples at different times after hospitalization by GC-MS and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Two subsequent 2-cm hair segments were also analyzed and tested positive for the above reported substances, evidencing repeated use. The matching quantitative results in all the analyzed biological matrices demonstrated that both analytical methodologies were suitable to correctly quantify NPS involved in the current intoxication. The objective assessment of acute and chronic intoxication by the above reported compounds demonstrate that the development of analytical methods aiming at the detection of a broad spectrum of compounds in conventional and non-conventional biological matrices is helpful when facing the new challenging threat of intoxications caused by NPS.
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http://dx.doi.org/10.1007/s00414-017-1648-9DOI Listing
November 2017

Cross-Reactivity of Chloroquine and Hydroxychloroquine With DRI Amphetamine Immunoassay.

Ther Drug Monit 2017 04;39(2):192-196

*Clinical Toxicology Unit, Clinical Analysis Department, Hospital Universitari Son Espases, Research Institute of Health Sciences (IdISPa), Palma de Mallorca, Spain; †Research Institute of Health Sciences (IdISPa), Palma de Mallorca, Spain; ‡Division of Emergency, Department of Paediatrics, Hospital Universitari Son Espases, Palma de Mallorca, Spain; §Department of Rheumatology, Hospital Universitari Son Espases, Palma de Mallorca, Spain; ¶Clinical Analysis Department, Hospital Universitari Son Lla[Combining Grave Accent]tzer, Palma de Mallorca, Spain; ‖Clinical Analysis Department, Hospital Can Misses, Ibiza, Spain; **Division of Emergency Laboratory, Hospital Universitari de Bellvitge, Barcelona, Spain; and ††Reference Laboratory, Barcelona, Spain.

Background: Chloroquine and hydroxychloroquine are medical drugs used to treat the chemoprophylaxis of malaria and a second-line anti-inflammatory drug.

Methods: We performed a study of cross-reactivity of chloroquine and hydroxychloroquine in the DRI Amphetamine Assay inspired by a case report of a self-ingestion of chloroquine after a family dispute, that involved the following: (1) an in vitro study with control samples of healthy subjects, (2) an in vivo study with samples of patients with rheumatoid arthritis, and (3) an evaluation of the cross-reactivity of chloroquine and hydroxychloroquine in 3 additional immunoassays.

Results: In the case report, the Amphetamine DRI assay resulted positive both at 1000 ng/mL cutoff (1507 and 1137 ng/mL) and at 500 ng/mL cutoff (1178 and 642 ng/mL). Chloroquine urine levels were 103,900 and 100,900 ng/mL at 5 and 9 hours after ingestion. The results with control samples showed a positive cross-reactivity of chloroquine in the DRI Amphetamine Assay (approximately 0.74% and 0.89% at cutoff of 1000 and 500 ng/mL, respectively). Hydroxychloroquine did not cross-react with the DRI Amphetamine Assay up to 1,000,000 ng/mL. In patients treated with chloroquine or hydroxychloroquine, DRI Amphetamine did not produce false-positive results. The comparative assay study showed a positive cross-reactivity of chloroquine in the Emit II Plus Amphetamines Assay with control samples.

Conclusions: Chloroquine can cause false-positive results in the DRI Amphetamine Assay when it is present at high concentrations. Hydroxychloroquine did not produce false-positive results neither in the DRI Amphetamine Assay nor in the others immunoassays evaluated.
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http://dx.doi.org/10.1097/FTD.0000000000000382DOI Listing
April 2017

Acute intoxication caused by synthetic cannabinoids 5F-ADB and MMB-2201: A case series.

Forensic Sci Int 2017 Apr 2;273:e10-e14. Epub 2017 Feb 2.

National Centre on Addiction and Doping, Istituto Superiore di Sanità, V.le Regina Elena 299, 00161, Rome, Italy.

Synthetic cannabinoids are relatively new substances of abuse. Recently, abuse of synthetic cannabinoids has been increasingly reported in the lay press and medical literature. When new compounds are introduced, their use is initially not restricted by prohibition therefore their consumption cannot be verified by standard drug tests. The use of these compounds among adolescents and young adults is constantly growing, making it important for emergency services to be familiar with the signs and symptoms of intoxication present. Overdose and chronic use of these substances can cause adverse effects including altered mental status, tachycardia, and loss of consciousness. Here, we report five cases of acute intoxication by synthetic cannabinoids 5F-ADB and MMB-2201 with analytical confirmation.
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http://dx.doi.org/10.1016/j.forsciint.2017.01.020DOI Listing
April 2017

Alimemazine poisoning as evidence of Munchausen syndrome by proxy: A pediatric case report.

Forensic Sci Int 2016 Sep 11;266:e18-e22. Epub 2016 Aug 11.

Clinical Toxicology Unit, Clinical Analysis Department, Hospital Universitari Son Espases, Palma de Mallorca, Spain; Research Institute of Health Sciences (IdISPa), Palma de Mallorca, Spain. Electronic address:

Munchausen syndrome by proxy (MSBP), also known as fabricated or induced illness in a child by a caretaker, is a form of abuse where a caregiver deliberately produces or feigns illness in a person under his or her care, so that the proxy will receive medical care that gratifies the caregiver. The affected children are often hospitalized for long periods and endure repetitive, painful and expensive diagnostic attempts. We present an analytically confirmed case of MSBP by alimemazine. A 3-year-old boy was brought repetitively to a Pediatric Emergency Department by his mother because he presented limb tremors, dysarthria, obnubilation, and ataxia and generalized tonic-clonic seizures coinciding with intermittent fever. Neither the rest of the physical examination nor the complementary tests showed any significant alterations. MSBP was suspected and a routine systematic toxicological analysis in urine and blood was requested. Alimemazine was detected in all biological samples. The administration of this drug was never mentioned by the mother and the subsequent interview with her corroborated the suspicion of MSBP. Clinically, after separation from the mother, the child's neurological symptoms gradually improved until the complete disappearance of the cerebellar symptoms. Alimemazine was quantified in serum, urine, gastric content and cerebrospinal fluid samples by gas chromatography-mass spectrometry (maximum serum level was 0.42μg/ml). Hair quantification of alimemazine was performed by ultra-performance liquid chromatography-tandem mass spectrometry in different segments of hair. The results confirmed regular substance use during the at least eight last months (8.8, 14.7, 19.7 and 4.6ng/mg hair starting from most proximal segment). This patient represents the first case published with analytical data of alimemazine in blood, urine, gastric content, cerebrospinal fluid and hair, which allowed us to prove an acute and repetitive poisoning with alimemazine as evidence of MSBP.
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http://dx.doi.org/10.1016/j.forsciint.2016.08.010DOI Listing
September 2016

Fenofibric Acid Can Cause False-Positive Urine Methylenedioxymethamphetamine Immunoassay Results.

J Anal Toxicol 2015 Nov-Dec;39(9):734-40. Epub 2015 Jul 22.

Servicio de Análisis Clínicos and Unidad de Toxicología Clínica, Hospital Universitario Son Espases, Instituto de Investigación Sanitaria de Palma (IdISPa), Carretera Valldemossa 79, Palma de Mallorca 07120, Spain

We present a false-positive result of ecstasy (3,4-methylenedioxy-NN-methylamphetamine) screening due to the therapeutic use of fenofibrate, an antihyperlipidemic drug. Our hypothesis was that the main metabolite of fenofibrate, fenofibric acid, was responsible for this cross-reactivity on a DRI(®) Ecstasy Assay, using a cut-off of 500 ng/mL. We estimated that the addition of 225 µg/mL pure fenofibric acid to blank urine would be sufficient to result in a positive DRI(®) Ecstasy Assay. The results obtained on the urine samples analyses of the patient show that the DRI(®) Ecstasy Assay resulted negative 2 days after discontinuing fenofibrate treatment, when the urine fenofibric acid concentration corrected by creatinine and determinated by gas chromatography-mass spectrometry was 20.3 µg/mg creatinine. The cross-reactivity data for fenofibric acid would seem to indicate that there was insufficient concentration of measured compound to account for the positive immunochemical results for ecstasy. This apparent discrepancy can be explained in several ways, one of them is that the β-glucuronidase-resistent fenofibric acid isomers are responsible. This process could explain the low recovery of free fenofibric acid when we use the developed method for its quantification in urine samples. Positive results on immunoassay screening must be considered presumptive until confirmation with another method based on a different principle, preferably gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry.
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http://dx.doi.org/10.1093/jat/bkv074DOI Listing
August 2016

Phytotherapy in a rat model of hyperoxaluria: the antioxidant effects of quercetin involve serum paraoxonase 1 activation.

Exp Biol Med (Maywood) 2011 Oct 5;236(10):1133-8. Epub 2011 Sep 5.

Energy Metabolism and Nutrition Research Group, Department of Fundamental Biology and Health Sciences, University Institute of Health Sciences Research, University of Balearic Islands, Cra. Valldemossa km 7.5, ES-07122 Palma de Mallorca.

Serum paraoxonase 1 (PON1) has been reported to be an important contributor to the antioxidant and anti-inflammatory activities of HDL, avoiding LDL oxidation. The activity of this enzyme is reduced in patients with renal insufficiency, caused by elevated oxidative stress and disturbances of apolipoprotein metabolism. Therapeutic utilization of antioxidants to control renal oxidative stress may be an effective therapy in renal protection. The aim was to investigate the protective effects of several antioxidant compounds against the oxidative stress associated to renal failure induced by ethylene glycol (EG), focusing on the possible role of serum PON1 activity. Fifty-four male Wistar rats were randomly assigned to six groups (n = 9): an untreated control (C) group, an EG-treated group, a catechin (CAT)-treated group, an epicatechin (EPI)-treated group, a quercetin (QUE)-treated group and a folk herbal extract (FHE)-treated group. After 16 d of treatment, calcium oxalate lithiasis was induced in the rats using EG. After eight days (treatment + EG), the animals were sacrificed. EG treatment impaired kidney composition, increased oxidative damage, and decreased serum paraoxonase and arylesterase activities. CAT, QUE and the FHE Fagolitos improved oxidative status by enhancing antioxidant defenses - superoxide dismutase and PON1 activities - and reducing oxidative damage, thus reinforcing the idea of a possible role of PON1 in the protective effects of QUE against the deleterious consequences of oxidative stress in kidney.
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http://dx.doi.org/10.1258/ebm.2011.011090DOI Listing
October 2011

Urinary lithogenesis risk tests: comparison of a commercial kit and a laboratory prototype test.

Scand J Urol Nephrol 2011 Nov 20;45(5):312-8. Epub 2011 Jun 20.

Laboratory of Renal Lithiasis Research, University Institute of Health Sciences Research, University of Balearic Islands, Palma de Mallorca, Spain.

Objective: Renal stone formation is a multifactorial process depending in part on urine composition. Other parameters relate to structural or pathological features of the kidney. To date, routine laboratory estimation of urolithiasis risk has been based on determination of urinary composition. This process requires collection of at least two 24 h urine samples, which is tedious for patients. The most important feature of urinary lithogenic risk is the balance between various urinary parameters, although unknown factors may be involved. The objective of this study was to compare data obtained using a commercial kit with those of a laboratory prototype, using a multicentre approach, to validate the utility of these methods in routine clinical practice.

Material And Methods: A simple new commercial test (NefroPlus®; Sarstedt AG & Co., Nümbrecht, Germany) evaluating the capacity of urine to crystallize calcium salts, and thus permitting detection of patients at risk for stone development, was compared with a prototype test previously described by this group. Urine of 64 volunteers produced during the night was used in these comparisons. The commercial test was also used to evaluate urine samples of 83 subjects in one of three hospitals.

Results: Both methods were essentially in complete agreement (98%) with respect to test results. The multicentre data were: sensitivity 94.7%; specificity 76.9%; positive predictive value (lithogenic urine) 90.0%; negative predictive value (non-lithogenic urine) 87.0%; test efficacy 89.2%.

Conclusion: The new commercial NefroPlus test offers fast and cheap evaluation of the overall risk of development of urinary calcium-containing calculi.
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http://dx.doi.org/10.3109/00365599.2011.584551DOI Listing
November 2011

Non-infectious phosphate renal calculi: fine structure, chemical and phase composition.

Scand J Clin Lab Invest 2011 Sep 26;71(5):407-12. Epub 2011 Apr 26.

Laboratory of Renal Lithiasis Research, University Institute of Health Sciences Research (IUNICS), University of Balearic Islands, Palma de Mallorca, Spain.

Background: Chemical composition of internally non-homogeneous phosphate stones should be related to the conditions prevailing during the formation of each individual part.

Objective: The object of this paper was to provide a detailed study of phosphate stone composition on the micro- and macro-scales.

Methods: Fine inner structure, chemical and phase composition of 10 phosphate calculi from different patients were determined by chemical (wet) analysis, observation by scanning microscope, semi-quantitative determination of Ca, Mg, P and C by energy dispersive X-ray and by X-ray diffraction. Results. Eight calculi are formed by amorphous calcium phosphate and two by hydroxyapatite. Magnesium was inversely related to Ca/P ratio. Point chemical composition of solid phase varies in wide limits, i.e. composition of calculus interior is highly inhomogeneous on the microscale. All studied calculi contained an abundance of organic matter incorporated in their volume; the content of carbon was double the calcium content in molar quantities.

Conclusions: Phosphate renal calculi with the low Ca/P molar ratio predominantly consist of amorphous calcium phosphate whereas those with a high Ca/P molar ratio are composed of poorly crystalline hydroxyapatite which can be partially carbonated. Magnesium may be an inhibitor of HAP formation from urine. Abundant organic matter incorporated into the calculus volume indicates its decisive role at stone formation. Variable point composition of stones implies widely varying conditions during their development.
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http://dx.doi.org/10.3109/00365513.2011.575952DOI Listing
September 2011

Origin and types of calcium oxalate monohydrate papillary renal calculi.

Urology 2010 Dec 13;76(6):1339-45. Epub 2010 May 13.

Laboratory of Renal Lithiasis Research, Faculty of Sciences, Universitary Institute of Health Sciences Research, University of Balearic Islands, Palma de Mallorca, Spain.

Objectives: Subepithelial hydroxyapatite calcification of renal papilla is thought to be involved in the formation of calcium oxalate monohydrate (COM) papillary calculi. To assess the mechanism of formation, we sought to correlate the fine structure of papillary renal calculi with specific pathophysiologic conditions and urinary alterations.

Methods: The study included 831 COM papillary renal calculi with established fine inner structures. A total of 24 patients with chronic stone formation were randomly selected, and their urine was collected and analyzed. The case history and lifestyle habits of these patients were obtained.

Results: The 831 papillary calculi could be classified into 1 of 4 main groups. Type I included small calculi in which COM columnar crystals begin to develop in the concave zone in close contact with papillary tissue. Type II calculi contained a hydroxyapatite core located in or near the concave zone. Type III consisted of calculi that developed on the tip of the papillae and in the concave zone, containing hydroxyapatite, calcified tissue, and calcified tubules. Type IV consisted of papillary calculi in which the core, which is situated near, but not in, the concave zone, is formed by intergrown COM crystals and organic matter. Many factors, including urinary alterations (eg, hyperoxaluria), associated diseases (eg, hypertension, diabetes), and consumption or exposure to cytotoxic substances (eg, analgesic abuse) were associated with these types of calculi.

Conclusions: Our findings have indicated that injury is the first cause of papillary COM calculus formation, with the location of the injury determining the morphology of the resulting calculus.
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http://dx.doi.org/10.1016/j.urology.2010.02.022DOI Listing
December 2010

Phytotherapy and renal stones: the role of antioxidants. A pilot study in Wistar rats.

Urol Res 2009 Feb 10;37(1):35-40. Epub 2008 Dec 10.

Faculty of Sciences, University Institute of Health Sciences Research (IUNICS), University of Balearic Islands, Palma de Mallorca, Spain.

Since ancient times, various herbal preparations have been used in renal lithiasis therapy, but conclusive scientific data on their therapeutic effects and efficacy are not available. To address this issue, the present study evaluated the antilithiasic activity of a traditional Mallorcan herbal preparation, and compared its effects with those of the antioxidant flavonoids, catechin and epicatechin. Thirty-six male Wistar rats were assigned randomly to four groups (n = 9): a control group, a catechin (CAT) treatment group, an epicatechin (EPI) treatment group, and a group treated with a folk herbal extract (FHE). After 16 days of treatment, calcium oxalate lithiasis was induced in the rats using ethylene glycol. After 8 days (treatment + ethylene glycol), 24-h rat urine was collected, the animals were sacrificed and their kidneys were removed for histological and chemical analysis. The calcium concentration in kidney tissue was significantly lower in the CAT-treated (2.4 +/- 0.3 mg/g), EPI-treated (1.8 +/- 0.3 mg/g) and FHE-treated (2.1 +/- 0.3 mg/g) groups, than in the control group (5.4 +/- 1.4 mg/g). Examination of paraffin-embedded kidney sections showed that control group rats had the greatest amount of calcification. There were no significant differences between control and treated groups with respect to urinary calcium, magnesium, oxalate and citrate concentrations. These results demonstrate the ability of herbal preparations and antioxidants to prevent the development of papillary and intratubular calcification in the kidney.
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http://dx.doi.org/10.1007/s00240-008-0165-1DOI Listing
February 2009
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