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Volume XVI, Number 1, 2012 - Therapeutics Pharmacology and Clinical Toxicology


Importance of molecular epidemiology of gram negative bacilli

Hristea Adriana, Olaru Ioana Diana, Niculescu Iulia, Arama Victoria, Jipa Raluca
Abstract: Resistant Gram negative bacilli have become a major concern. They are associated with increased mortality, prolonged hospitalization and increased costs. Carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumanii, extended spectrum beta-lactamase-producing Enterobacteriaceae have become increasingly common. A dramatic increase of CTX-M enzymes over TEM and SHV variants has recently occurred in Europe. There are considerable differences in beta-lactamase distribution between geographical areas as well as depending on the setting of infection. CTX-M type enzyme is considered to play an important role in community-acquired infections. Globalization and travel provide opportunities for the spread of resistant organisms responsible for infections that occur in hospitals as well as in community. Infections with carbapenem-resistant Enterobacteriaceae (CRE) are emerging as an important challenge in health-care settings. The potential widespread of carbapenem resistance via plasmids can lead to the spread of CRE into the community as well. Molecular epidemiology has proven very useful in detecting specific antimicrobial drug-resistance genes in a large number of organisms; it plays a key role in distinguishing between a pathogenic strain and a commensal contaminant, as well as between a relapse and a reinfection. Molecular biology typing techniques combined with epidemiological investigations also provide information about nosocomial pathogens and can be very useful for the implementation of effective infection control measures within the hospital environment. A comprehensive infection control program requires a sustained collaboration between infection control departments, clinical microbiology laboratories and hospital epidemiologist. Early detection of nosocomial drug-resistant pathogens through identification of pathogen clonality allows rapid intervention, which ensure the control of nosocomial infections.

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Viral respiratory co-infections. importance of newly discovered viruses in paediatric respiratory pathologies

Visan Angelica, Luminos Monica, Jugulete G., Negulescu Cristina, Draganescu Anca, Bilasco Anuta, Matei Roxana, Mantescu Domnita, Avram Carmen, Popescu Cristina, Merisescu Madalina
Abstract: Respiratory infections represent a major cause of morbidity and mortality in children. The roles of viruses such as respiratory syncytial virus, paraflu and adenovirus are well known in the etiology of respiratory infections. Lately, many studies displayed the implication of Rhinoviruses and Coronaviruses in inferior tract infections, where, sometimes, they can lead to a severe form of illness. Within the last decade, new respiratory viruses were discovered: human metapneumovirus, NL63 and HKU1 coronaviruses and human bocavirus. Viral co-infections are often seen in children hospitalized for acute respiratory infections, this causing more serious forms of disease that require hospital days. Multiplex PCR tests allow a simultaneous detection from the same sample of a large spectrum of viral and bacterial agents, which lay at the basis of respiratory infections.

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Therapeutic alternatives in osteoporosis after liver transplant

Motoi O., Ditoiu A. V. , Andronesi A. , Ismail G. , Voiculescu M.
Abstract: Hepatic osteodistrophy, one of the consequences of the continuous deterioration of liver function and chronic cholestasis, represents an important morbidity factor for patients waiting for liver transplant. Bone mineral density continues to decrease after transplant explaing the high incidence of fractures. Pretransplant osteodistrophy screening is mandatory and prophylaxis and treatment should be started as soon as possible to prevent further deterioration of BMD after transplant. Due to the specific problems encountered in liver cirrhosis, therapeutic alternatives must be carefully selected with a special regard to risk-benefit ratio.

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Original Papers

Acute toxicity investigation and the effects of original magnesium nanovesicles on the memory processes performance in rats

Tartau Liliana, Lupusoru Catalina Elena, Ciubotariu Diana, Melnig V.
Abstract: The purposes of this study were to evaluate in vivo acute toxicity of original magnesium chloride nanoparticulate formulations and to investigate their effects in cognitive processes in rats. The experiments were carried out on white Wistar rats (200-250g), divided into 3 groups of 7 animals each, treated orally (using an eso-gastric device), 7 consecutive daily administration as follows: Group I (Control): distilled water 0,1ml/10g weight; Group II (Mg): magnesium chloride 200mg/kbw; Group III (Mg ves): magnesium chloride 200mg/kbw entrapped in soft vesicles. At the end of the experiment, blood samples were taken from retro-orbital plexus to assess blood count, phagocytic capacity of peripheral neutrophils and serum complement activity, to investigate acute toxicity of the new nanoparticulate formulations. Spatial memory performance was assessed by recording spontaneous alternation behaviour in a single session in Y-maze. Experimental protocols were implemented according to recommendations of the University Committee for Research and Ethical Issues. Data were statistically analyzed with SPSS software for Windows version 17.0 and ANOVA one-way method. Results: Laboratory analysis showed no significant differences of blood count, phagocytic capacity of peripheral neutrophils and serum complement activity values, between new carrier formulations that entrapped magnesium chloride in lipid vesicles and non entrapped substance. Research results provided evidence that magnesium chloride entrapped vesicles, significantly increased spontaneous alternation percent in Y-maze test, which suggest the improvement of short-term memory. Conclusions: Biocompatibility evaluation proved that magnesium chloride lipid vesicles may be very suitable for in vivo use in the contexts of drug delivery systems. Oral administration during 7 days of soft vesicles entrapping magnesium chloride, 7 consecutive days administration of magnesium entrapped in lipid vesicles resulted in an enhancement of cognitive functions in rats.

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Metabolic disorder associated with HIV infection and atiretroviral treatment

Papita Anamaria, Itu Corina, Bolboaca D Sorana
Abstract: Introduction. Patients with HIV infection develop changes of lipid fractions. These changes are associated with both viral replication and antiretroviral treatments, especially with protease inhibitor treatments. The aim of the present research was to evaluate the specific risk factors of HIV infections for occurrence of lipid metabolism and glycemic metabolism disorders. Material and method. A longitudinal prospective study over a period of 34 months was carried out in order to assess 179 patients aged over 18, known or newly diagnosed with HIV infection. In these patients markers for HIV infection (viral load, CD4 cell, stage of disease, ARV treatment), lipid fractions (HDL cholesterol, LDL cholesterol, total cholesterol, triglycerides) and fasting plasma glucose were assessed. Survival studies were performed using the Kaplan Meier method at a significance level of 5%. Results. The evaluated group comprised 89 females with an age average of 30 ± 12.6 years and 90 males with an age average of 32.8 ± 12.7 years with or without ARV treatment. Most patients were in stage C3, followed by stage B2 and stage B3 of disease. Fasting plasma glucose proved to be increased in male patients (p = 0.00258). HDL cholesterol decrease in time in male patients (p = 0.00859), in presence of HIV replication (p = 0.00010), and in advanced immune depression (p = 0.00002). The HDL cholesterol proved not affected by the type of treatment (p = 0.52038). LDL cholesterol increase in presence of HIV replication (p = 0.000230, in advance immune depression (p = 0.03752), and in advanced stage of disease (p = 0.01210)). Total cholesterol was increased in presence of HIV replications (p = 0.00038) and in advance immune depression (p = 0.02560). Triglycerides increase in advanced HIV infection (p = 0.01458). Conclusions. Viral replications and advanced immunity depression is associated with decrease HDL-cholesterol and increase LDL-cholesterol and total cholesterol. The lipid fractions and fasting plasma glucose are not affected by the different type of treatment.

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Bone density screening in HIV infected romanian patients

Arbune Manuela, Nechita A.
Abstract: Evaluation of bone density in HIV patients is recommended by the present international guidelines for HIV management, but it is not a routine practice in Romania until now. The purpose of this study is to assess the prevalence of osteopenia in HIV+ patients from Galati- Romania. A cross sectional study of bone density mass evaluation by quantitative ultrasonography (QUS) measurements assessed 113 HIV+ patients without history of bone pathology, in comparison with 56 healthy volunteers (control group). Osteopenia was considered if Z-score of stiffness index was =-1. The prevalence of HIV related osteopenia is 29,2%, with higher frequency than in the control group (p=0,002; OR=4,78). Advanced HIV disease and HBV-coinfection increase the risk of HIV related osteopenia. Future health programs are necessary in order to prevent and monitor osteopenia in HIV+ Romanian patients.

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Risk factors and survival for pediatric human. immunodeficiency virus-related malignancy

Topor Laura, Nedelea S., Mardarescu Mariana
Abstract: Background: Prevalence of HIV-related malignancies is increasing along with higher survival time due to development of highly active antiretroviral chemotherapy. Risk factors for the development of HIV-related malignancies in pediatric population are less certain. Methods: This retrospective study involves 59 HIV-positive children admitted to the Matei Bals Infectious Diseases Institute from 1st of January 2005 to 1st of January 2010. Results: Even though there are differences in sex distribution, age, place of residence, duration of treatment, prior zidovudine use and viral load, these are not statistically relevant. Patients with low CD4 count have a two times greater risk for HIV-related malignancy development and a 4 times greater risk for death. Conclusions: Risk factors for the development of HIV-related malignancies are yet to be identified. A low CD4 count is an important risk factor both for malignancy and survival. The evolution of the two main malignancies is very different, with a much higher survival time for NHL than for Kaposis sarcoma.

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New tool in screening of congenital left heart defects

Albu D., Vladareanu R., Pelinescu-Onciul D.
Abstract: Spatiotemporale image correlation with color Doppler supplies the investigator with a volume dataset that gives infos regarding structure, blood flow dynamics and intracardiac flow. In this paper we discuss some cases of fetuses with left heart anomalies diagnosed by four dimensional ultrasound. The final aim of this new tool in ultrasound diagnosis is to raise the detection rate of congenital heart diseases by decreasing the dependency on operator abilities required by twodimensional ultrasound.

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Diagnosis and treatment of Hirschsprungs disease in children

Balanescu R., Topor Laura, Nedelea S.
Abstract: Background. Hirschsprung disease is a relatively rare condition, initially described as a cause of constipation in early infancy, and it is managed by pediatric surgeons. Significant advances have been made in understanding its etiologies in the last decade, especially with the explosion of molecular genetic techniques and early diagnosis. The surgical management has progressed from a two- or three-stage procedure to a primary operation. Methods. This retrospective study involves 74 patients diagnosed with Hirschsprungs Disease at the Surgery Clinic of -Grigore Alexandrescu- Emergency Hospital for Children from 1.1.2000 to 1.1.2011. For better analysis of diagnosis and treatment evolution, the group was split according to admission date into two smaller groups, each one containing 37 patients.Results. Age at dignosis has decreased in 2006-2011 interval, 32.4% of patients being newborns and 24.3% infants. In 2000-2005 only 24.3% were newborns and 21.6% infants. This results are correlated with a shorter hospital stay and period from diagnosis to surgery. Our results are all compared with the literature dates at the moment. Conclusion. Our clinic has improved its diagnosis and treatment methods for HD during the last 11 years. The age at diagnosis has decreased, along with the hospital stay and the time from diagnosis to surgery. Different procedures are used according to the case. As a result, patients are getting better and more suitable treatment with lower costs and lesser complications. Follow-up studies have shown very good results in long-term quality of life.

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Surgical treatment of eso-gastric cancer: abdominal approach vs. abdomino-thoracic approach

Ene D., Turculet C., Haiducu Carmen
Abstract: The surgical approach of eso-gastric tumours is extremely difficult because of the regional anatomical and functional particularities, thus deciding the correct surgical attitude is essential. Objective. The purpose of this study is to compare the surgical outcome of patients with abdominal approach of eso-gastric tumours versus the abdomino-thoracic one. Although tackling the oesophageal-gastric junction is difficult on its own, the main goals are a Ro resection and as little invasive operations as possible. Materials and method. Our study is an observational, retrospective study of immediate postoperative outcome in terms of morbidity and mortality. During 2000-2010, we assessed 79 patients, from the Clinical Emergency Hospital in Bucharest and the Clinical Hospital in Craiova, in terms of early postoperative outcome after eso-gastric cancer resection. We decided to enrol patients from two medical centres because of a low incidence of eso-gastric tumours in our country. Conclusions. The abdominothoracic approach should be avoided due to its major complications. The abdominal approach may be implemented in type I tumours as well, in addition to types II and III. The abdomino-thoracic approach allows a correct oesophageal resection above the tumour, as well as a thorough mediastinal lymph node dissection and it is mainly indicated in type Siewert I tumours. The operative mortality was 0% for both surgical approaches. The postoperative mortality rate was 15.18%.

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Therapeutical Practice

Therapeutic suggestions in occult chronic hypertransaminasemia

Nurciu Adriana, Olariu Cristina, Olariu M., Olteanu D.
Abstract: Less than 25% of asymptomatic adults have elevated levels of transaminases on a first evaluation, one third of these patients have normal values on a retest. From those who have elevated ALT on retest, some prove to suffer from an acute liver disease (with normal ALT in less than 6 months), and the others represent the category of chronic (more than 6 months) elevation of transaminases. The etiology of chronic hypertransaminasemia can be elucidated in 90% of the cases, due to liver disease with occult/ atypical evolution, or extra-hepatic causes of chronic elevation of transaminases. The 10% left represent the category of unexplained (obscure cause) elevation of transaminases. The occult/atypical evolution liver diseases are represented by chronic viral hepatitis (HBV, HCV), alcohol consumption, non-alcoholic steatohepatitis (NASH), congestion liver, drugs and liver toxic substances, autoimmune hepatitis, Wilson's disease, a1 antitrypsin deficiency, parasitic diseases. The extra-hepatic causes that can determinate chronic elevations of transaminases are haemolysis, soft muscle diseases (polymyositis), occult celiac sprue, suprarenal insufficiency, thyroid pathology. There still remains 10% of the patients in witch the etiology can not be explained. Usually these patients are kept under surveillance, periodic reevaluation, and undergo a second liver biopsy; witch may reveal nonspecific lesions, NASH, chronic hepatitis, cirrhosis. There are cases in witch on the surveillance period it was observed a spontaneous normalization of transaminases. Chronic hypertransaminasemia is quite frequent, and has a high addressability to the physician from patients with this type of pathology, being for most of them a discovery by chance on a routine blood check. It is also important to have a clear diagnosis to start the specific treatment for those patients who can benefit out of it as soon as possible.

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Case Report

Late presenter HIV positive patient with systemic cryptococcal infection - case review

Incze Andrea, Chiriac Carmen, Lucia Zaharia Kezdi, Iringo Sincu Nina
Abstract: Introduction. Late presenter HIV positive patients are characterized by low CD4+ lymphocyte count (below 350/mm3) at the moment of diagnosis, frequently having severe opportunistic infections associated. The aim of this study is to present the case of a patient recently diagnosed with HIV infection, with disseminated cryptococcal infection, cryptococcal meningitis and pneumonia. Methods. We studied the case of a 21 years old male patient, admitted for asthenia, fever, cough, dyspnea, thoracic pain, myalgias, arthralgias, headache, dizziness, vomiting, altered condition, with the impossibility of maintaining orthostatism, low body weight, oral thrush, and meningeal syndrome. Results. Following the paraclinical tests performed the diagnosis of HIV infection was established, with a CD4+ lymphocyte count of 7/mm3. Cryptococcus neoformans was cultivated from the blood and cerebrospinal fluid, and the chest x-ray revealed a bilateral bronchopneumonia. The outcome was favourable with Fluconazole monotherapy. Difficulties were encountered with the introduction of antiretroviral therapy due to the appearance of severe side effects to several drugs, and adherence problems, however, undetectable viral load was achieved. Conclusions. The management of late presenter HIV positive patient is challenging because of impaired immunity, associated opportunistic infections, and oncoming adherence problems. Widening of HIV testing to a larger area might conduct to a reduction in the number of late presenters, who require a complex therapy, high costs, and have poor prognosis.

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Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) caused by lamotrigine: a case report and brief review

Turcu G., Nedelcu Roxana Ioana, Forsea D.
Abstract: Drug rash with eosinophilia and systemic symptoms (DRESS) is a rare and life-threatening delayed drug hypersensitivity reaction characterized by cutaneous eruption, fever, lymphadenopathies and visceral involevment. The syndrome can result in multiorgan failure and patient death. Lamotrigine is a non-aromatic antiepileptic drug, effective for a broad range of seizures in adults and children, which is structurally and pharmacologically unrelated to other antiepileptic medications. Only several cases concerning DRESS syndrome associated with lamotrigine have been reportet in the literature. We report a case of hypersensitivity syndrome and important hepatic cytolysis induced by lamotrigine. A 26 year old female patient presented an episode of seizure with loss of conscience. CT, EEG and IRM studies performed were normal. Treatment with lamotrigine was prescribed. In the course of 28 days, the patient developed extensive erythematous macular rash and oral ulcerations, fever, lymphadenopathies, generalized myalgias and arthralgias, cephalea, pruritus and jaundice, periorbital and limbs edema, acute hepatitis. Serologic and laboratory tests showed no other causes responsible for the clinical spectrum. Hematologic tests revealed peripheral eosinophilia. Acute hepatitis was diagnosed. Lamotrigine medication was suspended and a systemic corticoid treatment was initiated, with progressively improved general condition of the patient. Lamotrigine treatment has been associated with multiorgan failure, DRESS syndrome, acute hepatic failure and disseminated intravascular coagulation. Detection of DRESS syndrome is dependent on the exclusion of a variety of diseases with similar manifestations and may be delayed in time. In conclusion, we suggest that these potentially fatal side effects should be considered in any patient with clinical deterioration following administration of this drug.

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Levosimendan for postoperative low cardiac output syndrome in a child with congenital mitral insufficiency

Vlad I. H., Buzoianu Anca Dana
Abstract: The treatment of low cardiac output syndrome after cardiac operations in children is a real therapeutical challenge. Usually cathecolamines and phosphodyesterase inhibitors are the drugs of choice. Levosimendan has also been used in this context but only in a small number of patients so the clinical experience is very limited. This paper presents the successful use of levosimendan in a pediatric patient with postoperative low cardiac output syndrome. The treatment with levosimendan, associated to a number of other drugs and therapeutic procedures increased the myocardial contractility, improved the cardiac output and eventually led to the patients complete recovery.

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