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Volume XV, Number 1, 2011 - Therapeutics Pharmacology and Clinical Toxicology


Phenotypic methods for detection of beta-lactamase-mediated resistance in E coli and Klebsiella pneumoniae

Mirela Flonta, Ariana Almas
Abstract: Enterobacteriaceae are major pathogens in both hospital and community. Recently the number of MDR phenotypes (multi drug resistant) increased, with the emergence of XDR phenotypes (extremely drug resistant - susceptible only to colistin and tigecycline). It is extremely important to detect and correct the reporting mechanisms for resistance. Many clinical laboratories have problems detecting extendedspectrum beta-lactamases, class C beta-lactamases and carbapenemases. Confusion exists regarding the importance of these resistance mechanisms, optimal testing methods and appropriate reporting conventions. Failure to correctly detect these enzymes contributed to their spread and sometimes, to inappropriate use of antibiotics. Clinical laboratories need to have expertise to provide a rapid and clinically relevant antibiogram result in hospitals where these resistance mechanisms are encountered. This review aims to summarize the most important methods for detection of extended spectrum ß-lactamases, class C beta-lactamases and carbapenemases. We studied recent a d relevant literature retrieved from PubMed and the internet.

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The antiinflammatory effect of H1 antihistamines in allergic rhinitis

Corina Bocsan, V. Cristea
Abstract: Allergic rhinitis is an immune inflammatory process, IgE mediated, which affects nasal mucosa. The immune allergic response presents 3 phases and involves many cells and mediators. Interleukins are involved both in producing and maintaining this process. Il-1, Il-6 and TNF-a increase allergic inflammation and are involved in producing the late phase of inflammation. The studies regarding unique or continuous exposure to specific allergens of the patients with allergic rhinitis revealed the increase of the proinflammatory cytokines level both in nasal secretion and in plasma. Histamine is the main mediator involved in allergic rhinitis through type 1 specific receptors. H1 antihistamines are first line treatment in all forms of allergic rhinitis. New generation antihistamines possess some anti-inflammatory properties, especially relevant in vitro studies and sometimes in vivo studies.

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Original Papers

Late Diagnosis of HIV Infection in Iasi County

A. Vata, Carmen Manciuc, Cristina Nicolau, L. Prisacariu, Luminita Vata, Carmen Dorobat
Abstract: Late diagnosis of HIV infection has unfavorable repercussions on both the patients themselves, due to higher morbidity and mortality rates, and the society as a whole, given the higher infection transmission risks and increased therapy and recovery costs. Material and methods. Our paper tackles a retrospective study conducted on naive patients that have entered the records of the Regional HIV/AIDS Center of Iasi in the last 10 years (2001-2010), based on the initial clinical, laboratory and therapeutic data found in the follow-up records of these patients. Late diagnosis was established when the patient presented for care with a CD4 count below 350 cells/mL or having an AIDS-defining condition. Results. 73.4% of the 192 patients included in the study were considered late presenters (58.5% with advanced HIV infection), according to the latest consensus definition. The average age of late presenters was 23.7 years, 53.9% of them being born between 1988 and 1991; M/F ratio - 1.3, U/R ratio - 1.14, average CD4 number - 130.8/cmm. The factors usually associated with late diagnosis in literature (age over 30 years, males, hepatitis co-infection) had no statistical significance in our study group. Mortality rates were considerably higher in late presenters (31.9 vs. 7.8%, p=0.002) and were correlated with a low initial number of CD4 (p<0.001), younger age (p=0.004); 57.8% of the deaths occurred within 6 months from diagnosis. ARV therapy was started by combining 2 NRTIs and PI in 52.7% of the patients, 2 NRTIs and one NNRTI in 32.1% of them, while raltegravir was only used in 3 patients. Conclusions. late diagnosis rates were higher in Iasi County than in literature, while the risk factors detected by other authors had no statistical significance, possibly due to the regional epidemiological specificity.

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Extrapulmonary tuberculosis in HIV infected patients

V. Gheorghita, Cristina Loredana Benea
Abstract: We would like to present the case of a 44-year old man, who was admitted and diagnosed in our hospital with HIV infection (stage C2) with abdominal tuberculosis as AIDS defining disease, oral candidiasis and deep venous thrombosis (tibial vein). We initiated standard tuberculostatic treatment with four first line drugs and after two weeks we started antiretroviral therapy (ARV) with Zidovudine (ZDV), Lamivudine (3TC) and Efavirenz (EFV). We recorded a rapid growth of CD4 to 296/mmc, with immune reconstitution syndrome (IRIS). In the next two weeks, the patient developed severe neuropsychiatric events most likely induced by EFV, ARV therapy thus ceased. Four months later with relative clinical favorable evolution a new viro-immunological evaluation was performed, with CD4 211/mmc and HIV RNA 5,9 log 10 cp/ml. ARV therapy was resumed with Abacavir (ABV), 3TC and Raltegravir (RAL) in double dose (800 mg BID) with good tolerance and rapid immunological and virological response. In conclusion, Raltegravir stands as an alternative for HIV patients, naive or experienced, with pulmonary or extrapulmonary tuberculosis, being a potent antiretroviral with favourable profile concerning tolerability and drug interactions.

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Assessment of hepatic encephalopathy in children with liver cirrhosis

B. A. Stana, Laura Bozomotu, Evelina Moraru
Abstract: Evolution of liver cirrhosis in children is accompanied by occurrence of complications of portal hypertension. Hepatic encephalopathy (HE) is not yet fully characterized and evaluation methods are still being perfected. Aim: To evaluate incidence and classify HE in a cohort of cirrhotic children. Materials and methods: The retrospective study was done upon 42 children diagnosed with liver cirrhosis. Assessment of HE was made by clinical elements and using a battery of psychometric tests. Results: HE was found in 67% of children with cirrhosis, 48% exhibiting minimal HE detected only by rigorous psychometric testing. No difference in HE score was observed in patients undergoing surgery, before and after the procedure. Conclusion: HE should be rigorously evaluated in children with liver cirrhosis, due to its important incidence and implications in the future of those children.

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Blunt abdominal trauma: severity factors in hollow viscus injuries

Ioana Iftimie-Nastase, M. Beuran
Abstract: The purpose of this paper is that of assessing the prognostic factors of gravity for patients with blunt abdominal trauma and associated hollow viscus and mesentry injuries, as well as evaluating the efficiency of imaging methods as diagnostic tools in these cases. Patients and methods. This paper is a mixed cohort study, both retrospective and prospective, between 2004 and 2012, being currently underway. The patients included in the study are multiple trauma patients admitted in the ICU and surgical wards of the Clinical Emergency Hospital, Bucharest. The patients included in the study were victims of motor vehicle accidents, assaults, falls from height, etc. and their inclusion in this study relied on predetermined criteria. Conclusions. Hollow viscus injuries are the main concern in blunt abdominal trauma patients with associated visceral lesions, including those treated non-operatively, since clinical examination is notoriously unreliable in making a diagnosis in these cases and imagery tools may also provide equivocal results, leading to blank laparotomies or missed hollow viscus injuries, which in turn lead to an increased rate of complications: hemoperitoneum/peritonitis- MOFS-death.

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D-Penicillamine and Zinc therapy for Wilsons Disease

V. Militaru, T. Pop, Lucian Burac, N. Miu, Ana Stefanescu, Florentina Claudia Militaru, Ioana-Corna Bocsan, Anca Buzoianu, C. Duncea
Abstract: Wilsondisease (WD) is a rare genetic autosomal recessive condition characterized by Copper overload. Its treatment uses chelating agents (mainly D-Pencillamine) and drugs which lower the intestinal absorption of Copper (Zinc). We hypothesized that the drugs are efficient if they induce hepatic and/or neurological amelioration; the greater the efficiency, the shorter the period of time to the amelioration. On a group of 16 patients consulted or hospitalized in Cluj-Napoca (Romania) we compared the hepatic biochemical normalization and the neurological amelioration in the patients receiving Zinc monotherapy (7 patients) vs. association of Zinc and D-Penicillamine (9 patients). The results were in favor of the association of the two drugs, but the only parameter reaching statistical significance threshold was the time to hepatic and neurological amelioration (p = 0.023). There were no severe adverse effects of either drug. The small sample size might have reduced the chances to have more significant differences, issue to be addressed by further studies. We concluded that the association of D-Penicillamine and Zinc is safe and efficient in treating Wilsons disease.

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Genotype-phenotype correlations between the alleles of the MDR1 C3435T polymorphism and pharmacokinetic parameters in Romanian epileptic patients

A.D. Buzoianu, I.C. Bocsan, C. Maier, A.P. Trifa, R.A. Popp, L. Perju Dumbrava, O. Sabin, C. Militaru, E. Brusturean, Z.Z. Major, C. Popescu
Abstract: The aim of the study was to evaluate the influence of MDR1 C3435T polymorphisms on the bioavailability of valproic acid (VPA) and the correlation between the genotype and the plasma levels. Materials and method: 60 patients with epilepsy, with a mean age of 37.15±12.76, evaluated in the Neurology Clinic of Cluj-Napoca were included. All patients were under stable VPA treatment for at least a month. Steady state plasma concentrations were determined using the GC/FID technique. We considered therapeutic level between 50-100 µg/mL. Using the PCR-RFLP method for each patient we have determined allelic variant of MDR1 C3435T polymorphism. Results. 71.7% of the patients had therapeutic level of valproic acid, 13.3% supra-therapeutic and 15% sub-therapeutic level of VPA. 13.3 % of the patients present CC genotype, while 58.3% present CT genotype and 28.3% TT genotype. The mean VPA plasmatic level is lower in patients with CC genotype, but with no significance, compared with TT and CT genotypes. There was no significant correlation established between the presence of C3435T polymorphism and sub or supra-therapeutic level of VPA. Conclusions. The polymorphism of MDR1 gene has no influence on the VPA serum level.

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Therapeutical Practice

Local anesthetic techniques in dermatology

Monica Darmanescu, V. Trifu, Sorina Chivu, Rodica Sotcan
Abstract: Local anesthesia is preferred for most cutaneous surgical procedures, because it reliably provides effective anesthesia. Several local anesthetics with various methods of delivery are available for the expanding field of cutaneous surgery. Understanding the pharmacological properties, different applications and proper technique of administration of local anesthetics allows for an efficient anesthesia and patient safety. The use of combined techniques of topical anesthetics, nerve blocks, local infiltration and tumescent anesthesia allows for effective cutaneous surgical procedures avoiding the increased risk of morbidity and mortality associated with general anesthesia.

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Toxic coma in children - etiology and clinical diagnosis

Simona Stanca, Madalina Petran, C. Ulmeanu, Viorela Nitescu
Abstract: Coma is a medical emergency that requires rapid and precise evaluation, especially in a Pediatric Emergency Department. Consciousness refers to the state of awareness of self and environment. Evaluation of consciousness in the pediatric patient must consider age and the appropriate developmental level. Coma is caused by multiple conditions that affect the brainstem or cortex diffusely. In the etiology of coma there are two large categories of coma: traumatic and non traumatic. Each of them includes a lot of cases. Coma is often a manifestation of life-threatening conditions. Therefore, the first evaluation of the child begins with vital functions stabilization and identification of immediately reversible causes. After stabilization we have to obtain a detailed history and perform a full physical examination. The physical exam can be crucial in finding the toxicants involved. Poisoning is the main cause of coma in children admitted and treated in Emergency Clinical Hospital for Children Grigore Alexandrescu.

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The core-values construction of the physician - patient communication, respective of the patients age

Maria Dorina Pasca
Abstract: Doctor - patient communication represents a test on both sides, so that healthy issues must be solved together. Taking into consideration the age particularities of patients represents a step forward in decrypting a behavior, an attitude and the cognoscible process of human value. The doctor must personalize the strategy of communication and the relation with patient having in mind the age particularities and considering the main elements of communication: to be understood, heard, accepted and receiving a feedback. In this context the value and the efficiency of communication has educational value, making the relation between transmitter and receiver doctor-patient or patient-doctor a special and a very important one because the patient is a human being not an object.

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Palliative Care in HIV from Theory to Practice

Cristina Nicolau, Carmen Manciuc, J. L. Prisacaru, Alexandra Largu, A. Vata, Carmen Dorobat
Abstract: Introduction: Palliative care associates a wide range of therapies designed to ensure the improvement of the quality of life of HIV seropositive patients. Objectives: To underline the importance of medical and non-medical palliative care measures (with multidisciplinary implications) in the treatment of the HIV infected patient. Material and method: The evolution of an HIV seropositive patient was analyzed, from the time of detection (2005) until 2009, dynamically following the clinical - immunological and psychological curve. Initial denial of the diagnosis (which caused the late arrival in our department) marked the further progress of the case. The patient required a prolonged period of hospitalization (45 days) and sustained medical support, which involved a multidisciplinary team, joined with psychological counseling with the aid of the family, various health professionals and representatives of the church. Conclusions: establishing a partnership relationship between doctor and patient by integrating concepts, principles and practical rules of palliative care in HIV are important in the approach the HIV infected patient.

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Case Report

Building the future on past remains case presentation of HIV multiexperienced patient

Daniela Ioana Munteanu, Raluca Mihailescu, Anca Streinu Cercelž Victoria Arama
Abstract: Introduction - HAART history is a history of changes, each new antiretroviral combination represents a chance to obtain viral undetectability. Objective - case presentation of HIV multiexperienced patient with virological failure, which belongs to the Romanian cohort of children and adolescents parenterally infected before 1990. Case presentation - we report the case of a 27 year old female, HIV positive since 1998 (at the age of 15 years), F genotype. First, she was diagnosed in B2 CDC clinico-immunological stage with 380/mmc CD4 count and HIV viremia of 5120 c/ml. The antiretroviral therapy was initiated in 1998, according to that time guidelines, first IDV+AZT+DDC, then EFV+3TC+d4T, NFV+DDI+d4T, LPV/r+NFV+3TC, LPV/r+SQV+3TC. Since 2001 the viremia remained detectable all the time, despite her good compliance to multiple antiretroviral regimen. In 2006, the CD4 count declined below 200 cell/mm3 and therefore a salvage therapy was introduced TPV/r+3TC+T20, but the viral replication persisted (HIV-RNA 243.179c/ml). The resistance tests performed in this case showed multiple mutations with decreased susceptibility to all available drugs. In 2008, new drugs became available on Romanian pharmaceutical market and other combinations were built, first RAL+DRV/r+3TC+T20 and then RAL+DRV/r+3TC+MVC+ETR and consequently the viremia became undetectable (May 2010 HIV-RNA <150c/ml, CD4 cell count 366/mm3). Conclusions - the patient represents an HIV multiexperienced case, with virological failure, despite good adherence to therapy. This case was among the first in our country who received new molecules, such as RAL, MAR, ETR and obtained the undetectability after 11 years of persistant viral replication. The new antiretroviral drug classes represent a step forward to obtain a durable viral suppression in multiexperienced patients with several resistance mutations.

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Attaining viral suppression in an HIV treatment experienced patient with persistent virological failure

Ioana D. Olaru, Adriana Hristea, Victoria Arama, Raluca Mihailescu, Daniela I. Munteanu
Abstract: Virological failure in treatment-experienced HIV patients is often due to the presence of resistance mutations acquired during therapy. With the discovery of new antiretroviral (ARV) drugs new options for the management of these patients emerged. Case presentation. We present the case of a 45-year-old treatment-experienced, female patient diagnosed with HIV infection in 1997. Throughout almost the entire duration of her follow-up, her HIV viral loads were consistently detectable. Her CD4 count was relatively stable and she did not experience any significant clinical events. Resistance tests performed predicted reduced response to all 3 major ARV classes. Adherence to therapy was reportedly inadequate during the first years. Only when novel treatment options became available, could our patient finally attain virological suppression and an increase in CD4 count was observed. The treatment regimen on which undetectability was reached comprised the integrase inhibitor, raltegravir, boosted darunavir and enfuvirtide. Additionally, an improvement in the patients lipid profile was also noted after switching from the previous regimen which had included 2 boosted protease inhibitors. Conclusions. Novel agents can prove extremely useful for treatment-experienced patients, allowing them to attain virological suppression in the setting of multi-class resistance. Adherence to therapy is essential. Additionally, the beneficial effect on lipids of these agents vs. other ARVs is not to be neglected.

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Challenges in the diagnosis of mother-to-child Toxoplasma gondii infection

Mihaela Bujor-Moraru
Abstract: We present the case of a newborn from a mother infected with Toxoplasma gondii during pregnancy. Born alive, the baby presented multiple organ failures, which in the end, despite of the treatment, led to his death. This case report is very instructive, and proves once again not only the necessity of assessing the possible teratogenic infections in pregnant women, but also the key role of prenatal investigations and of the risk factors.

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