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Volume XIV, Number 3, 2010 - Therapeutics Pharmacology and Clinical Toxicology


Best practice for retaining patients in substitution therapy

A. O. Abagiu
Abstract: Objective: To emphasize the best practice approach issues for retaining addicted patients onsubstitution treatment in an outpatient center. I have done a literature search of MEDLINE/PUBMED, CINAHAL and COCHRANE COLLABORATION using the following search terms: retention, substance abuse outpatient treatment, best practice. Study Selection: Pertinent English-language human studies and book chapters from 01.01.2004 until 31.12.2008 were reviewed. Data Synthesis: The main issues found in the literature regarding the improvement of retention in treatment and correlated with treatment management are: higher rather than lower doses of methadone, multiple interdisciplinary assessment approach with concomitant psychotherapy and rehabilitation counseling, family or close relatives involvement and location of the unit nearby or better within a hospital. We want to emphasize that other existent factors correlated with better retention like older age, less contact with the criminal justice system and former participation in an MMT cannot be improved in designing the model for a best practice facility. Conclusions: Best issues for retaining patients on maintenance treatment are mainly: integrated multidisciplinary approach, usage of rather higher doses of treatment, family or close ones involvement and placing the facility within a hospital.

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Current strategies and concepts for preventing infections after solid organ transplantation

M. Oltean
Abstract: The posttransplant immunosuppressive medication renders transplant recipients susceptible to bacterial, viral or fungal infections. A significant proportion of these infectious complications can be successfully prevented through careful donor and recipient screening, pretransplant infection control and immunizations. Moreover, an array of measures in the posttransplant period such as antiviral prophylaxis as well as simple yet meaningful changes in the lifestyle can further contribute to decreasing the frequency of infections. This not exhaustive review outlines these main measures and highlights the current prevention strategies, based on the available data, consensus and protocols.

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Original Papers

Is the Human Leucocyte Antigen B*5701 predicted by sequence variations of HIV-1 subtype F Reverse Transcriptase?

D. Florea, D. Otelea, Simona Paraschiv, Mihaela Fratila, A. Streinu-Cercel
Abstract: Objective: to evaluate the predictive value of mutations in position 245 of HIV reverse-transcriptase as a marker of the presence of HLA-B*5701 in HIV-1 subtype F1 infected patients. Methods: HIV drug resistance testing was performed by using the ViroSeq Genotyping System. Sequence-based HLA typing was used for detection of HLA-B*5701. Results: A high sequence conservation in HIV reverse-transcriptase codon 245 was found both in treatment-naive and in treatment-experienced patients. Wild-type sequence was present in all 4 patients with B*5701, but also in 109 (98.1%) of 111 subjects without B*5701. There was no significant association between HLA-B*5701 and mutations in HIV reverse-transcripase codon 245. Conclusions: Sequence variation in HIV reverse transcriptase 245 position is not a useful marker for predicting HLA-B*5701 in subtype F infected patients.

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Physical-chemical properties and biological activity of new Thioureides compounds with potentially antimicrobial activity

V. Ordeanu, V.A. Voicu, Gh. Taralunga, M. Necsulescu, Angela Postoarca, Diana Popescu, Lucia E. Ionescu, Simona N. Bicheru, Cristina Secara, B. Patranichi
Abstract: The study presents a concise selection of applicative research of pharmaceutical microbiology for the purpose of testing the biological activity of certain new thioureides having potentially anti-infectious effects. Objectives: the synthesis, the physical-chemical analysis and biological testing of the thioureides of the 2-(4-ethyl-phenoxymethyl)-benzoic acid (3 series), screening on aerobic bacteria, anaerobic bacteria, viruses, fungi, yeasts, spores and toxins, testing the anti-microbial effect according to the current European norms, acute toxicological testing on laboratory animals, comparing the results and statistical processing for the classification in pharmacological groups. The majority of the tested amides presented anti-bacterial effect; however, this was unequal, varying from very weak to very good; we deemed very weak the average effect occurring by the inhibition area having a diameter smaller than or equal to 6 mm (i.e. the substance application area), weak, good equivalent to the standard sample and very good higher than this value. We registered 6 substances having an effect. The effect is better on the Gram-positive bacteria, rather than on the Gram-negative ones, almost double, which could lead us to conclude that the effect would take place via the alteration of the bacterial wall structure, probably through the inhibition of the peptidoglycan synthesis. On average, the value of the diameter of the inhibition area of thioureides batch 2 as weighed against the standard bacteria tested, as compared with the mean for the phenol sample 5%. The compounds tested do no indicate antifungal, antiviral, sporicidal or anti-toxin effect.

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Experimental research on the action of Ketoprofen and the association of Ketoprofen and Enalaprilat on the thermoalgesic sensitivity in naive and ethanol-treated rats

Maria Magdalena Pastramagiu, O. C. Mungiu
Abstract: The aim of this study is the experimental research of the influence of Ketonal and combination of Ketonal and Enap on nociception in naive and ethanol treated rats. Materials and methods: We used male Wistar rats divided in two groups: naive rats and ethanol treated rats (10% solution of alcohol, for three weeks). Both groups received intraperitoneal Ketonal 1 mg/kbw, and Ketonal (the same dose) in combination with Enap (20 µg/kbw). The control group received distilled water. Nociception was investigated through the hot plate assay, at 15, 30, 60, 90 minutes after the administration of substances. The results were statistically analyzed using the Anova test, followed by the post-hoc test. In conclusion, we have found Ketonal antinociceptive effect, both in naive and in ethanol treated rats, more evident in the first case. The association of Ketonal with Enap produced analgesia in naive animals and nociception in the case of alcohol fed rats.

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Prognostic value of plasma adiponectin in type 2 diabetic dialysis patients

Ina Maria Kacso, Alina Lenghel, I. M. Patiu, Simona Racasan, R. Orasan, Crina Claudia Rusu, Diana Moldovan, Cosmina Ioana Bondor, Cristina Nita, N. D. Hancu, Mirela Gherman Caprioara
Abstract: Background: Adiponectin, an insulin-sensitizing, anti-inflammatory and antiatherogenic adipokine, seems to conserve its protective effect against cardiovascular complications in dialysis patients. In diabetic dialysis patients however results are less consistent, higher adiponectin levels being associated with mortality. We intend to study the prognostic value of plasma adiponectin for atherosclerotic complications and all-cause mortality in type 2 diabetic patients on hemodialysis in a multicenter trial; we hereby present our pilot study. Material and methods: All (28) diabetic patients on maintenance hemodialysis in our center were included in the study. History, clinical data, routine laboratory assessment and total plasma adiponectin were obtained. Patients were compared to a control group of 20 nondiabetic hemodialysis patients. During 1 year of follow-up, new occurrence of cardiovascular complications due to atherosclerosis (myocardial infarction and revascularization, amputation or revascularization due to arteriosclerosis obliterans, stroke) and all-cause mortality were recorded. Results: Type 2 diabetic dialysis patients had lower adiponectin levels than dialysis controls (21.08±3.17/ml versus 39.00±10.11µg/ml, p=0.03). In simple regression, adiponectin was correlated to body mass index (r=-0.43, p=0.01) and serum triglycerides (r=-0.62, p=0.0003); in multiple stepwise regression, triglycerides remained the only predictor of plasma adiponectin (p=0.01). Adiponectin levels were higher in women than in men (28.73±5.76 µg/ml versus 15.33±2.88 µg/ml, p=0.03). There was a statistically significant difference in plasma adiponectin levels between patients with proliferative retinopathy and patients without this condition (27.22±4.87 µg/ml versus 16.46±3.91 µg/ml, p=0.02). Patients with new onset of cardiovascular events had lower adiponectin levels than controls (12.76±3.52 µg/ml versus 23.34±3.81 µg/ml but the difference did not reach statistical significance, probably due to the small number of patients. Baseline adiponectin was higher in deceased patients than in survivors (29.87±10.32 µg/ml versus 19.61±3.29 µg/ml); again, statistical significance was not reached due to the small cohort. The number of patients to be included in the multicenter trial in order to attain statistical significance for each arm of the above mentioned comparisons was calculated. Conclusions: In diabetic patients treated with hemodialysis, lower adiponectin levels were found in patients with new onset of complications of atherosclerosis, while increased adiponectin might predict all-cause mortality. Further large-scale prospective studies are required to confirm these findings.

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HIV Infection in the Oltenia Region at the beginning of the XXIst Century

A. Cupsa, Andreea Cristina Stoian, Florentina Dumitrescu, Irina Niculescu, L. Giubelan, Cristina Iocu, Amalia Romanescu
Abstract: Objectives: Epidemiological analysis of newly reported cases of HIV infection in the Oltenia region. Material and methods: Retrospective study of the Craiova Regional Center for Monitoring and Evaluation of HIV/AIDS from 01/01/2007 to 31/12/2009, in a group of 113 patients (Px), representing newly diagnosed cases with HIV infection. Results: During 2007-2009, the newly detected cases of HIV infection were chronologically divided as follows: 35 cases in 2007, 46 cases in 2008, 32 cases in 2009. The average age of Px was 24.59 years [limits 0.33-55], distribution by sex: F/M = 61/52 (53.99% F, 46.01% M). At the time of diagnosis, the average CD4 count was 209.22 cells/mm≥ [limits 1-977], average HIV-RNA copies per mL= 4.9 lg [limits 1.69-6.31]. Distribution by clinical staging and immunological classification in HIV-related disease was as follows: 13 Px (11.50%) - A1, 15 Px (13.27%) - A2, 5 Px (4.42%) - A3, 11 Px (9.73%) - B2, 18 Px (15.92%) - B3, 2 Px (1.76%) - C1, 6 Px (5.30%) - C2, 43Px (38.05%) - C3. AIDS was diagnosed in 65.48% Px. Distribution by transmission route is: 50.45% - sexual, 45.13% - parenteral, 1.76% - vertical, 2.66% Px - unknown transmission route. Pregnant women were 15.29% of total new detected cases, which represents 29.5% of the total new cases in women. Anti-HIV antibody testing was performed for screening (employment, admission examination) in 3.53% cases. Opportunistic infections present at the time of HIV infection diagnosis were mostly represented by tuberculosis - in 27.43% Px. Conclusions: 1. In the Oltenia region, the number of the newly detected cases of HIV infection, in the last years, remains at a low but steady rate, a sign that in this area there are still major components in the complex epidemiologic process. 2. Increased frequency of HIV infection in women advocates predominantly for sexual transmission, the horizontal transmission to child, almost exclusively encountered during 1987-1990, having completely disappeared. 3. Late detection, in many cases related to the presence of opportunistic infections, leads to postponement of ARV therapy initiation and growth potential of HIV transmission in the community.

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Aspects of adherence to treatment in community pharmacy

Aura Rusu, G. Hancu, Maria Dorina Pasca
Abstract: Adherence to treatment, patient cooperation and compliance, means the use of a specific drug by the patient, following the prescription and the medical advice. In contrast, non-adherence means the habitude of the patient who does not follow medical recommendations. In the present work, we present a study of adherence to treatment performed on 100 patients diagnosed with chronic illnesses who require permanent or long-term administration of medication (hypertension, coronary heart disease, dyslipidemia, bone and joint diseases, diabetes, epilepsy). The study was performed in three community pharmacies from Targu Mures. Our objective was to analyze and evaluate adherence to treatment in patients with chronic conditions in community pharmacies. The method used was questionnaire. We analyzed omissions in medication, compliance regarding number of doses and indicated concentration, compliance regarding the period between administrations, use of drugs for purposes other than prescribed, administration of the medicines in concordance with the main meals. Another aim is to establish the main source of information about the prescribed medication (general practitioner, specialist physician, and pharmacist). It was established that the phenomenon of non-adherence to treatment is a big concern among chronic patients, and the information about the prescribed medicines is received mainly from the general practitioner or specialist physician. The results show that involvement of pharmacists in counseling patients was minimal.

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Study of the phenotypic variation expression in the metabolizing status of romanian epileptic patients

Bocsan Corina Ioana
Abstract: Aim of the study. The present study oversees the influence of CYP polymorphisms on the metabolism of VPA and the correlation between the genotype and the plasma levels. Materials and method. 46 patients either with idiopathic or secondary epilepsy, with a mean age of 37,37 ± 1,87, 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 weve determined allelic variant of CYP2C19*2 and CYP2C19*3. Results. 65% of the patients had therapeutic level of valproic acid, 15% supra-therapeutic and 20% sub-therapeutic level of it. 23,91% of the patients were heterozygous for CYP2C9*2 and 19,57% CYP2C9*2 for CYP2C9*3. Regarding CYP2C19*2 15,22% were heterozygous and 8.70% homozygous. Allele CYP2C19*3 was absent. There were no significant correlation established between the genetic metabolizer status and its phenotypic expression represented by the plasma concentrations. Conclusions. The metabolizer status defined by the different allelic expression of CYP2C9 and CYP2C19 doesnt present statistically significant influences on VPA steady-state plasma concentrations.

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Therapeutical Practice

Neurocognitive impairment in a newly diagnosed HIV positive patient with advanced disease

Adriana Hristea, I.D. Olaru, M. Lazar, M. Ion, Ana Maria Petrescu, Victoria Arama, Ruxandra Moroti
Abstract: Central nervous system involvement is relatively common in HIV infected patients ranging from subclinical neurological impairment to progressive dementia with a major impact on daily life and severe and potentially fatal opportunistic infections. We discuss the case of a newly diagnosed patient with advanced HIV infection presenting with neurological symptoms and a mild cognitive impairment. He had a low CD4 count (47 cells/mm3) and high plasma and cerebral spinal fluid viral loads (414.382 copies/ml and 141.040 copies/ml, respectively). The MRI showed symmetric periventricular white matter lesions. Findings were consistent with the diagnosis of HIV-associated mild neurocognitive disorder. New classification of the HIV-associated neurocognitive disorders and current treatment recommendations are also discussed.

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Macrophage Activation Syndrome in two girls with Systemic Lupus Erythematosus

N. Iagaru, D. Oraseanu, F. Rusu, Monica Luminos, Anca Draganescu, Anca Ghit
Abstract: Background: Most frequently seen in Systemic Arthritis - Juvenile Idiopathic Arthritis, macrophage activation syndrome (MAS) may also be a life-threatening complication in juvenile systemic lupus erythematosus (SLE). The diagnosis of MAS may be particularly challenging because it may mimic the clinical and laboratory features of the underlying disease. Objective: To describe the clinical and laboratory features of MAS as an early complication of juvenile systemic lupus erythematosus. Methods: We report two cases of females with MAS in Juvenile SLE occurring acutely in the first 6 months after the onset, at the time of first presentation in our hospital. The clinical features and laboratory data were analyzed. The main laboratory findings of MAS were present: pancytopenia, abnormal serum hepatic enzyme levels, coagulopathy, neurologic symptoms, hyperferritinemia, hypertriglyceridemia, decreased erythrocyte sedimentation rate, hyponatremia, hypoalbuminemia and macrophage hemophagocytosis in the bone marrow aspirate sample. The treatment included intravenous methylprednisolon, immunoglobulins, cyclophosphamide pulse (one case), transfusions (PT, FFP, PRC) and supportive therapy. Conclusion: The diagnosis of MAS can be difficult because some of its clinical features overlap those of lupus itself. The occurrence of unexplained fever and pancytopenia associated with increased hepatic enzyme levels, coagulopathy, hyperferritinemia should promptly raise the suspicion of macrophage activation syndrome.

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Case Report

Miliary generalized tuberculosis with subacute evolution

Ruxandra Laza, A.Crisan, Emilia Nicoara
Abstract: Tuberculosis continues to be - the most lethal disease caused by a single pathogen. The patient that we presented displayed a lot of factors involved in maintaining or re-emerging of tuberculosis infection as a disease (the presence of a low socio-economic level, lack of medical supervision and subsequently extension of a tuberculosis process). The initial clinical diagnosis was meningo-encephalitis syndrome, taken as a probably tuberculosis meningo-encephalitis based on CSF examination. It finally proved to be an extensive tuberculosis: meningeal, pulmonary, urogenital, endocrine. Death occurred on the tenth day of hospitalization and specific treatment, and it was preceded by the appearance of a purpuric syndrome, hepatic cytolysis and azotemia, interpreted as iatrogenic drug reaction.

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