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Volume XX, Number 1, 2016 - Therapeutics Pharmacology and Clinical Toxicology


Taxonomy of the updated definition and staging criteria of bacterial sepsis

Merisescu Madalina, Luminos Monica
Abstract: Sepsis can be easily defined as an exaggerated inflammatory response to a pathogen’s aggression. Due to its severity that caused increased rates of mortality, research entities mobilised impressive human and material resources in order to reach and establish rapid and safe diagnostic methods. By setting a rapid diagnosis, the proper etiologic treatment can be applied thus lowering complications and severity occurring in a sepsis case. Recently, at the Third International Consensus Definitions for Sepsis and Septic Shock held in February 2016, new scores and criteria were established in order to define and stage sepsis as accurately as possible. The new approach excludes the classical terms of systemic inflammatory response syndrome (SIRS) and includes new criteria, grounded by the PIRO concept, enabling a correct evaluation of intensive care patients, which also asses the host’s susceptibility, infection degree, response and affected organs. The objective of this study is to present the new definitions and staging criteria for bacterial sepsis and their benefitst.

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Original Papers

Performing simultaneous detection of BCR-ABL and JAK2V617F mutation represents an improvement for a more accurate and less time consuming Myeloproliferative Neoplasms diagnosis

Ilea Anca, Vladareanu Ana Maria
Abstract: This article presents observations made following a more comprehensive study which analyzed the results of molecular tests performed for the diagnosis of myeloproliferative neoplasms in a molecular biology laboratory over a period of seven years (January 2009- December 2015).The laboratory is an ELN (European Leukemia Net) certified diagnostic laboratory for quantification of BCR-ABL.Two diagnosis tests (for BCL-ABL transcript and Jak2 V617F point mutation) were performed on a number of 614 patients with various chronic myeloproliferative neplasms subtypes. 320 (52%) patients were found to be Jak2 V617F positive, 25 (4.07%) were found to be BCR-ABL positive. A “double negative” was found in 262 (42.67%) patients and 7 (1.17%) patients were positive for both Jak2V617F and BCR-ABL. The results are consistent with other similar works from the scientific literature and demonstrate the importance of molecular testing for an accurate diagnosis and a correct assessment of the clonal character of proliferations. Also, due to the particular situations , the simultaneous performance of both screening tests in the diagnosis of CMN is highly recommended.

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Biochemical correlations in polytrauma patients with unstable pelvic fractures

Lupescu Doriana, Dimitriu A., Lupescu Olivera, Nagea M., Ciurea N., Grosu Alina, Greabu Maria
Abstract: Polytrauma represents an association of multiple injuries capable of inducing a systemic response and resulting in a life-threatening condition. Regardless of the different approaches and definitions, the severity of this association, determined by a specific pathophysiology, requires special therapeutic protocols, adapted to the status of the patient. One of the most challenging situations for the trauma specialists is represented by polytrauma with unstable pelvic fractures - the stabilization of these fractures is considered a resuscitative measure, but this must be done while avoiding the “second hit” phenomenon. These can be achieved by adapting the treatment to the patient’s systemic response to aggression, which has to be evaluated by objective means. The authors perform a retrospective study in a Level 1 Trauma Centre in order to analyse the possibility of using biochemical markers to asses the status of the polytrauma patients with unstable pelvic fractures and to establish their treatment.

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Markers of inflammation in crushing trauma of the lower limbs

Dimitriu A., Lupescu Olivera, Ciurea N., Nagea M., Pătru Cristina, Popescu Gh.I., Lupescu Doriana
Abstract: Crushing traumas are produced by high-energy traumatic agents and are thus characterized by severe and complex injuries, affecting all the structures of the involved limb. Vascular, bone or nerve injuries may occur, but the main characteristic of crushing is “rhabdomyolysis”- destruction of the skeletal muscles. If not treated before irreversible changes appear, the necrotic muscle will endanger not only the vitality of the limb, but also the life of the patient, due to systemic toxaemia. A complex interdisciplinary approach is thus necessary in order to insure the survival and recovery of the patient. Research has been done regarding objective monitoring criteria able to guide the treatment. Certain biochemical markers have been described as useful and the authors evaluate their clinical significance in patients with crushing trauma in a Level I Trauma Centre. The results of this retrospective study support the data presented in the literature regarding the correlation between the outcome of these patients and their biochemical profile.

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Therapeutical Practice

Boron neutron capture therapy delivery agents used in boron administration

Gales N. Laurentia, Anghel M. Rodica
Abstract: Boron neutron capture theory (BNCT) is a binary therapy applied in malignant tumours, resis-tant to other treatment methods, namely chemotherapy and radiotherapy. One of the main components is Bor-10, a stable isotope that can be inserted in the tumour cells by using specific transporters. Through the use of adequate Boron compounds, that preferably are located in the tumour cells and not in the healthy tissue, Boron neutron capture therapy provides a higher curative potential with minimal toxicity, at the level of normal tissues. In order to obtain a proper tumour control with minimum side effects, 10B increased concentrations should be obtained by selective cumulation within the tumour cells, with an adequate ion gradient between the normal and tumour tissues. Therapeutic effectiveness can be reached by a minimal boron concentration of 20-30 ppm inside the tumour and a tumour/blood and tumour/normal tissues boron concentration gradient of approximately 3. So far, clinical practice has used two main boron delivery agents: sodium borocaptate (Na2B12H11SH) (BSH) and a phenylalanine dihydroxy-boryl derivative, known as Boronophenylalanine (BPA). During the past 20 years, along with the development of new techniques of chemical synthesis and improved knowledge of biological and biochemical require-ments for the effectiveness of an agent and ways of boron delivery, a new number of boron delivery agents have appeared in response to the agents up to now. They include: aminoacids, nucleic acid precursors, DNA-binding molecules, porphyrin derivatives, high-molecular- weight delivery agents, macromolecules or nanovehicles such as monoclonal antibodies or monoclonal antibody fragments that bind to tumour epitopes- EGF, VEGF or liposomes, dendrimers, dextrans, polylysine, avidin, folic acid, etc. Next to the identification and study of new boron compounds or new compound combinations, other delivery methods are currently under research seeking to improve the classical intravenous administration and the selective intratumoral binding process as well as the therapeutic index (intraarterial, intratumoral administration, etc). Despite a large number of ongoing studies, a boron compound that fits all the ideal BNCT compound criteria has not yet been identified, especially in terms of tumour selectivity, the ratio of concentrations between the concentration in the tumour cells and the one in the normal cells, the delivery of a proper number of boron atoms in the tumour cells, hydrophilicity and lipophilicity, homogeneous intra-tumour distribution. The development of BNCT boron delivery agents has been initiated approximately 50 years ago and continues to represent at the same time a priority and a difficulty. Several bor-10 boron based pharmaceutical products have been prepared in view of their potential use in BNCT.

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Case Report

Free peritoneal perforation in Crohn s disease-a rare complication

Dimitriu Anca, Gheorghe C.
Abstract: Free peritoneal perforation is a rare complication of Crohn`s disease. We report the case of a 17 years-old male patient with Ileocolonic and perianal Crohn`s Disease , severe ileitis nonresponsive to anti-TNF alfa medication, who underwent a laparotomy surgery for acute abdomen and was found to have ileal perforation for which segmental enterectomy with ileotransversoanastomosis was performed. The most likely hypothesis is a bowel dilatation above a stenotic area which increased the intraluminal pressure or the inflammatory changes in the blood vessels associated with enteritis possibly contributing to an ischemic cause . Due to high risk of postoperative recurrence of the disease, anti-TNF alfa thearpy was restarted at the same dose at 1 month after surgery. The patient had good early and late postoperative outcomes.

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Clinical evolutive aspects and neuroimaging findings in a child with herpes simplex virus type I encephalitis

Luminos Monica, Draganescu Anca, Visan Angelica, Vasile Magdalena, Negulescu Cristina, Merisescu Madalina Maria, Kouris Camelia, Schiopu Sabina, Osman Endis, Bilasco Anuta
Abstract: Herpes simplex encephalitis (HSE) is a severe viral infection of the central nervous system and it’s one of the most common causes of life-threatening fulminate necrotizing viral encephalitis. Most frequently the patients’ presentation is a non-specific one, consisting of fever, headaches, vomiting, focal neurological signs, and seizures in association with an altered consciousness. The management of HSE has been improved in the last years through the availability of intravenous acyclovir therapy and PCR - based diagnostic assays, reducing mortality and morbidity rates and decreasing rates of neurological sequelae. The objective was to expose clinical data, laboratory test sequencing and management courses in HSE among children - a clinical case report. We present the case of a 15 month-old boy, admitted in the ICU of National Institute for Infectious diseases “Prof. Dr. Matei Bals” for fever, vomiting, diarrhoea, focal and generalized seizures, drowsiness, bulging anterior fontanel and altered mental status. The diagnosis of HSE was established corroborating data from the clinical findings with the neurological exam, and confirmed by detecting the HSV type I DNA in CSF using PCR; Brain MRI was highly suggestive for HSE.The patient was treated with i.v Acyclovir; anticonvulsant drugs , anti cerebral-edema therapy and i.v human immunoglobulin. The child was discharged after 25 days with a good clinical and neurological condition. HSE is the most common cause of sporadic fatal encephalitis worldwide and it’s a medical emergency that requires etiological treatment right away. Using PCR for detecting HSV -DNA from CSF remains the gold standard for diagnosing HSE. Mortality rates range dramatically depending on how early the antiviral treatment is initiated.

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Recurrent Bacterial Meningitis Due To Transethmoidal Nasal Meningoencephalocele in an Adult Patient

Gavriliu Liana-Catalina, Benea Otilia-Elisabeta
Abstract: Recurrent bacterial meningitis is a less common clinical entity, but it is usually more challenging for the clinician because it requires a thorough investigation of any predisposing factor. We report the case of an adult patient with a history of recurrent bacterial meningitis. Following extensive investigation for underlying predisposing factors, we found a malformation of the central nervous system as the cause of his recurrent meningitis. With the appropriate antimicrobial treatment the patient improved and he was referred to a neurosurgical department in order to solve his anatomic defect.

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An overlooked aetiology of chronic arthritis in children

Iagaru N., Olteanu B.
Abstract: TB arthritis is a rare, insidious chronic mono-arthritis resulting in extremely serious destruction of joints and bones. Usually, the possibility of TB arthritis is suggested by family infectious or environmental contact with TB and a positive Test at PPD. The Objectives. Are to discuss about a forgotten etiology of monoarthritis in pediatric patients. The author presents the case of a teenager girl (16 ½ years old) with chronic arthritis of the wrist treated for 6 months in other hospitals, at the onset as acute rheumatic fever and then, as juvenile idiopathic arthritis, oligoarthritis subtype. Although no infected family or environmental contact is known, no predisposing factors, and pulmonary TB are absent, the evolution refractory to treatment with severe joint damages demands a Quantiferon TB Gold Test that comes positive. Surgical evacuation of pus and quadruple tuberculostatic therapy had a favourable outcome with restitution ad integrum.

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