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Volume XVI, Number 4, 2012 - Therapeutics Pharmacology and Clinical Toxicology


Vitamin D and tuberculosis. A ten year review

Moroti-Constantinescu V. Ruxandra, Hristea Adriana, Aram Victoria, Olaru D. Ioana
Abstract: Numerous studies investigating the link between vitamin D deficiency and tuberculosis (TB) have been published in recent years. The objective of this review is to assess the associations between serum vitamin D concentrations or vitamin D supplementation and active or latent TB. We performed a PubMed database search of studies published during the last 10 years involving human subjects. Secondary research articles, case reports, in vitro studies and studies performed on animals were excluded. We identified 33 articles meeting our selection criteria, of which 26 were observational studies and 7 were randomized controlled trials assessing the effect of vitamin D supplementation. Vitamin D deficiency was highly prevalent across populations from different geographic regions. Most studies have found an association between vitamin D deficiency and active TB. Vitamin D deficiency was also found to be linked to a longer time to sputum conversion and worse outcomes in patients with TB, as well as an increased frequency of tuberculin skin test conversion in contacts of patients with active TB. Vitamin D supplementation might also lead to improved outcomes in patients with TB.

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New strategies in prevention and therapy of allergic contact dermatitis

Constantin Maria Magdalena
Abstract: Allergic contact dermatitis is an inflammatory process resulting from contact of a certain substance called allergen with the tegument, which undergoes specific reactive changes. Allergic contact dermatitis is based on the pathophysiological mechanism of delayed hypersensitivity (type IV reaction), reaction typically exemplified by allergic eczema determined by contact with poison ivy. In allergic contact dermatitis, the basis for therapy is the recognition of the causative allergens, very useful in providing the chance to avoid exposure to these harmful substances. Complete therapy management of this allergic eczema consists in recognize the allergen, remove it, reduce the inflammation and restore the skin barrier. Nowadays, prevention strategy is very complex and important, the preventive measures can be divided into primary, secondary and tertiary, different levels of prevention often coincide.

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Original Papers

Monocyte chemotactic protein-1 in HIV infected patients

Mihailescu Raluca, Tiliscan C., Aram Victoria, Streinu-Cercel A., Ion Daniela, Aram S. St.
Abstract: Even under current combined antiretroviral therapy, residual HIV replication maintains a chronic inflammation state in seropositive patients. The profile of different biomarkers of inflammation and also their clinical impact in multifaceted HIV pathology are still incompletely elucidated. This article reviews the contribution of monocyte chemotactic protein -1 in the pathogenesis of neuroinflammation, cardiovascular damage and metabolic impairment in HIV-infected patients. Identifying pathophysiological mechanisms of MCP-1 may help researchers to further evaluate its clinical relevance, its utility as adiagnostic tool and its potential as a therapeutical target for people living with HIV.

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Combinations of multiple cancers in ENT area

Cataloiu (Heroiu) Adriana - Daniela, Popescu C.R.
Abstract: Background: Second primary tumours develop in approximately 4 - 6% in patients with ENT cancers. Most affected by the occurrence of multiple cancers is the aero digestive tract, perhaps because this mucosa is exposed to the same carcinogens (tobacco smoking and alcohol consumption). Still random combinations of multiple cancers may occur. Methods: Between 1 January and 31 December 2011, we met, in ENT Hospital Coltea, twenty-eight cases of multiple cancers in ENT area, most of them affecting the aero digestive tract and a small number of these were random associations. Results: Twenty-two cases were combinations of multiple cancers of upper digestive and respiratory tracts, for example: larynx and amygdala, larynx and nasopharynx, larynx and tongue, etc. But six of these cases were associations of two tumours most likely without any connections with each other. We met cancer of upper digestive and respiratory tracts in combination with cancer outside ENT area: urinary bladder, non-Hodgkin`s malignant lymphoma, and breast. Conclusions: Multiple cancers are quite frequent entities in the aerodigestive tract. Rare combinations of multiple cancers have a special place between multiple cancers of ENT area, because so far, no causal relationship between them has been demonstrated, as in those of aero digestive tract.

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The impact of nucleos(t)ide analogues treatment

Gheorghita I. V., Caruntu A. Fl., Curescu Manuela, Ion St., Streinu-Cercel A.
Abstract: A number of studies have shown that serum HBsAg appears to correlate with intrahepatic cccDNA level as well as transcriptional activity of the cccDNA and can be considered a surrogate marker of infected cells. The aim of this study was to assess the patterns of change in HBsAg levels in HBeAg negative CHB patients treated with Entecavir (ETV) for 96 weeks. It is a prospective, observational, noninterventional study of a series of cases initiated in September 2009. Five consecutive patients diagnosed with CHB HBeAg negative were included in this study. Patients were treated with ETV at a dose of 0,5 mg/day (n=4) and respectively 1mg/day (n=1) for 96 weeks. The mean value for the main baseline parameters were 75.2 IU/ml for ALT, 4.4 log10 IU/ml for q-HBsAg and 7.6 log10 IU/ml for HBV DNA. This patients did not have a significant change in their HBsAg levels during 96 weeks of ETV treatment (mean decline was 0.150 log10 IU/ml, p=0.615). In conclusions our small study reveals that in e-antigen negative chronic hepatitis B patients the levels of q-HBsAg were not influenced by the prolonged treatment with one of the most potent antiviral oral drugs, despite a fast and complete viral suppression.

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Tertiary oximes on brain acetylcholinesterase and central excitatory eects of nerve agents

Shih Tsung-Ming, Koenig A. Jerey, McDonough H. John
Abstract: Organophosphorus nerve agents irreversibly inhibit the enzyme acetylcholinesterase (AChE), which leads to an excess of the cholinergic neurotransmitter acetylcholine in the synapses causing numerous toxic effects, including prolonged seizures and subsequent neuropathology. Current nerve agent therapies include pralidoxime (2-PAM) to reactivate inhibited AChE. The quaternary structure of this oxime does not allow it to cross the blood brain barrier (BBB) to reactivate brain AChE and to mitigate CNS toxicity. This study examined whether monoisonitrosoacetone (MINA) and N,N-diethyl-3-(2-(hydroxyimino)acetoxy) propan-1-aminium chloride (DHAP), two tertiary oximes that can penetrate the BBB, could prevent or reverse the central toxic effects of three nerve agents, sarin (GB), cyclosarin (GF), or VX, in guinea pigs. The first experiment tested whether MINA and DHAP could reactivate brain and peripheral tissue AChE inhibited by these nerve agents. Animals were challenged with a 1.0 x LD50 subcutaneous dose of a nerve agent and followed 15 min by one of 5 test doses of the oxime. Animals were euthanized 45 min after oxime treatment when blood and target tissues were collected. AChE activity was measured using the Ellman assay. MINA produced a dose-dependent AChE reactivation in both brain and peripheral tissues following all 3 nerve agents. DHAP reactivated GB-inhibited AChE in brain and peripheral tissues, but only GF-and VX-inhibited AChE in peripheral tissues. In a second experiment, the ability of MINA and DHAP to block or terminate nerve agent-induced electroencephalographic (EEG) seizure activity was evaluated. Animals instrumented to record brain EEG activity were challenged with a seizure-inducing dose (2.0 x LD50) of GB, GF, or VX, and oxime was administered one min after nerve agent exposure. MINA prevented or terminated seizures elicited by all three nerve agents. DHAP was effective against GB-induced seizures, but not against GF- or VX-induced seizures. Animals in which an oxime either prevented or terminated seizures almost invariably survived and lost significantly less body weight, when compared to those animals that experienced seizures that were not controlled by oxime treatment. In summary, the capacity of a tertiary oxime to reactivate nerve agent-inhibited AChE in the CNS was strongly associated with its ability to prevent or stop nerve agent-induced seizure activity. Therefore, reactivation of nerve agent-inhibited brain AChE using a CNS active oxime provides substantial therapeutic benefits and can reverse the neuro-excitatory sequelae of nerve agent intoxication.

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Should we be concerned about the ingestion of unidentied plants?

Krenzelok E. P., Mrvos R.
Abstract: Inquiries about plant exposures are common calls to poison information centers.1 The majority of inquiries involve the ingestion of a plant, the identity of which is generally known by a common or botanical name.2,3 However, a challenge to specialists in poison information (SPI) is the management of patients who have ingested plants that are unidentified or if it is unknown whether the plant is toxic. The purpose of this project was to investigate the morbidity and mortality associated with the ingestion of unidentified plants and those in which the toxicity was unknown.

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Comparative ecacy of antipsychotics: results of one-year observational study

Dima Lorena, Vasile D., Voicu V.A.
Abstract: Treatment of schizophrenia and related disorders poses significant problems to both patients and clinicians, being therefore an area of extensive research. Improved knowledge on treatment response and its evolution in time is a prerequisite for improving therapeutic strategies for people with schizophrenia and related disorders. The aim of the present study was to compare the efficacy of haloperidol, olanzapine, risperidone, quetiapine, and aripiprazole in patients with schizophrenia or related disorders, assessed in routine clinical settings. Material and methods. The study was designed as a 12 months prospective observational study of 131 patients with schizophrenia or related disorders treated with one of the five antipsychotics. Positive and Negative Syndrome Scale (PANSS) scores and sub-scores, Clinical Global Impression (CGI) severity and GAF scores were assessed and registered at inclusion, at discharge, at 6 and 12 months, during scheduled visits. The results of treatment efficacy assessment revealed significant decrease of the total scores for psychopathology (PANSS) and severity of illness (CGI), and the increase of the overall functioning scores (GAF) for the five treatment groups over the 12-months follow-up (p <0.001). There were no significant differences among the treatment groups in mean change from baseline of total PANSS, general symptomatology PANSS sub-score, CGI severity or GAF scores at 12 months. Mean change from baseline of positive PANSS score was highest in olanzapine group, significant higher than in the aripiprazole (p p=0.002) and quetiapine (p=0.006) groups. In case of negative PANSS score, mean change from baseline at 12 months was lowest in the haloperidol group, significantly lower than the correspondent mean in the quetiapine group (p=0.006), and of borderline statistical significance lower compared to aripiprazole group (p=0.05). Conclusion, The differences detected should be interpreted with caution given the observational design of our study and cannot be generalized, but they do sustain the idea that antipsychotics, older or newer, are a heterogeneous group of compounds. Further studies are needed to understand the heterogeneity of treatment response, which might guide a rational and individualized selection of antipsychotic for better outcomes in patients with schizophrenia and related disorders.

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Evaluation and modeling of kinetics of Aluminium in plasma and dialysis fluid

Paun S.C., Tudosie M.S., Macovei R., Ardelean Luminia, Bumbea Viorica, Caragea Genica, Ionica M., Mircioiu C., Piperea-Sianu A., Mladin C.
Abstract: Paper investigated kinetics of Aluminium levels during renal dialysis. Plasma and dialysis fluid levels of Aluminium where evaluated using an Atomic Absorption Spectrometry method. Evaluation included determination of mean blood level of a control group and a chronic renal failure patients group. It was found that plasma levels of Aluminium (21.7 ± 22.5 µg/L) were significant higher in patients than in control group (4.07 ± 0.51 µg/L). Concentration of Aluminium in dialysis fluid was two times lower than mean concentration in blood (8.78 ± 8.90 before dialysis and 9.0 ± 13.2 µg/L after dialysis). The difference between the mean concentrations at the beginning and at the end of dialysis was not significant. Consequently, the main source of Al seems to be the blood in the case of uraemic patients and the dialysis work as a -detoxification- method. In conditions of replacing tap water for dialysis with purified water obtained with reverse osmosis the main Al flux is from blood to dialysis fluid.

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Quality of life in HIV AIDS patients

Borduselu Matilda, Mardarescu Mariana, Ungurianu Rodica, Petre Cristina, Draghicenoiu Ruxandra, Tudor Ana-Maria, Matei Carina, Streinu-Cercel A.
Abstract: Introduction: The quality of life of people with HIV/AIDS has been improved dramatically in the HAART era, the morbidity and the mortality decreasing significantly, however it still remained below the general populations one. Objectives: Global assessment of quality of life in multi-experienced people living with HIV/AIDS and identification of its influencing factors. Methods: The study was conducted on 80 subjects, including 60 multi-experienced patients with HIV/AIDS diagnosed for at least 10 years, monitored by INBI "Prof. Dr. Matei Bals" and 20 subjects with similar age from the general population, without HIV infection. The method of evaluation was composed of structured self-assessment questionnaires on quality of life, pain, fatigue, general symptoms, adherence to antiretroviral therapy and a semi-structured interview. In addition the subjects were evaluated for depression. Between the laboratory tests we retained viral load and immunological status. Results: Using the SF-36 questionnaire and considering a threshold of 80 points for a good quality of life, the number of persons with HIV infection with low quality of life was three times higher than those without HIV infection. (OR = 4.93, p = 0.01). In people with HIV/AIDS, the severity of pain, as well as the severity of fatigue, were correlated with a lower quality of life (p <0.0001). Likewise a low score of quality of life was associated with presence of depression (RR = 2.82, p = 0.0001). In the control group we found only mild pain and the depression was present in one case associated with decreased quality of life. The impact of fatigue was three times higher in people with HIV/AIDS than in the control group. Unlike literature, in our study was found by regression analysis a significant negative correlation between viral load and quality of life score (r = -0.44, r^2 = 0.21, p = 0.0019). Also it was found a correlation between quality of life and CD4 count. Good adherence to treatment was associated with a better quality of life at the same threshold over 80 points on the SF-36 test. (OR = 4.68, p = 0.005). Conclusions: Pain, depression and fatigue are three factors which, in association with the direct effect of HIV, have tremendous impact about quality of life for people living with HIV/AIDS. Besides etiopathogenic treatment, evaluation and correct treatment of these factors can improve the quality of life of patients with HIV/AIDS and can lead to increase adherence to antiretroviral treatment.

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The profile of cytokines involved in the inflammatory response in acute viral hepatitis type A

Horvat Melinda, Tatulescu Doina, Cismaru Cristina, Mundean Monica, Lupse Mihaela, Carstina D., Iacob Daniela, Valeanu Madalina, Slavcovici Adriana
Abstract: Background and Aims. Hepatitis A virus, the most common cause of acute viral hepatitis has an immunologically mediated mechanism of liver injury. The aims of our study were to determine the profile of the serum cytokines in acute hepatitis A (AHA) patients and to compare this profile in severe versus medium forms. Methods. This prospective study was carried out in the Infectious Diseases Department, Cluj-Napoca, Romania. Twenty patients were divided into medium and severe forms, based on prothrombin time (PT) and INR. The evaluated serum cytokines included: interleukin (IL)-6, the tumor necrosis factor a (TNF-a), interferon ? (IFN-?), IL-ß, IL-1 receptor antagonist (IL1-Ra) and IL-10. Results. We found statistically significant differences (p<0.01) between the concentrations of IL1-Ra, IL-10, IL-6, TNF-a in AHA patients versus control group. For IL-ß (p 0.29) and IFN-? (p 0.15) no statistically significant differences were reported between these two groups. A negative statistically significant correlation between PT and IL-1Ra (r -0.56, p 0.01) and IL-10 (r -0.43, p 0.05) was found. IL-1Ra has the highest diagnostic value and is statistically significant for severe AHA forms with an AUC of 0.75, a sensitivity of 90% and a specificity of 90% at a cut off value of 1929.44 (p 0.04). Conclusions. The significantly higher value of AUC, sensitivity and specificity for serum IL-6, TNF-a, IL-10 and IL-1Ra demonstrate the simultaneous presence of the pro- and anti-inflammatory response in AHA. The serum levels of IL-1Ra and IL-6 were significantly higher in the severe forms than in the medium forms of AHA. Our study demonstrates that increased serum levels of IL-1Ra represents a biomarker associated with the severe forms of AHA.

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Therapeutical Practice

Surgical treatment of hallux valgus in children and teenagers

Ulici Al., Balanescu R., Topor Laura, Barbu M.
Abstract: Hallux valgus is a relatively often met illness with onset in childhood or adolescence. The appearance of a deformity (bunion) at the level of the head of the first metatarsus with the deviation of the hallux in valgus and of the first metatarsus in varus is the initial aspect of clinical manifestation. Even if initially the deformity is asymptomatic, sooner or later it becomes painful, with difficulties in walking and sometimes, when the bunion is too big, restraining the type of footwear. Actually esthetic distress is the main symptom that makes the patient go to the doctor. For the asymptomatic forms, classic, the treatment is conservative and consists in adding of a bolsterer in the shoes for the anterior arch. This could assure a better function and prevents the early aggravation of the deformity. For the forms with important deformity and symptoms the surgical treatment is recommended. The aim of this article was to standardize the treatment of hallux valgus in children and teenagers for the main clinical forms.

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Treatment of hepatitis C in children

Pacurar Daniela, Lesanu Gabriela, Ion Gabriela, Oraseanu D.
Abstract: Chronic hepatitis C represents a worldwide viral epidemic. Children represent only a small proportion of the hepatitis C virus (HCV)-infected population. The natural course of hepatitis C is less understood in the pediatric population, nevertheless, a substantial number of children have chronic HCV infection and are at risk of complications. There are a number of differences in HCV infection between children and adults. Children are less likely to have symptoms, more likely to have spontaneous viral clearance, and more likely to have normal aminotransferase values; they also have a slower rate of advancement to end-stage liver disease. Treatment for children aged 3 to 17has been different during the past 20 years; three forms of therapy have been approved over time: interferon monotherapy, interferonalpha and ribavirin combined therapy, and pegylated interferon and ribavirin combined therapy. Current guidelines recommend that children are to be treated for HCV infection using the same principles applied in adults. Pegylated interferon (PEG-IFN) alpha-2b and ribavirin (RBV) is the standard of care for adults with chronic hepatitis C and is now approved for the treatment of children as well. The issue of treating chronic hepatitis C is in constant flux. There is highly active clinical research in this area and new medications will be approved for the treatment in the future.

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Emergency treatment of cholinesterase inhibitors poisoning in children

Ulmeanu Al. I., Nitescu Viorela, Petran Madalina, Stanca Simona, Vivisenco Iolanda, Crisan Veronica, Ulmeanu C.E.
Abstract: Acute poisoning with cholinesterase inhibitors still represent an important problem in children poisoning. Although in the last few years there was a decrease in the incidence of this type of poisoning, organophosphate and carbamate intoxication still has a very severe prognosis. The clinical severity depends on the type of product ingested, age, and early initiation of antidote therapy. The use of atropine is essential in the first 24-48 hours for the prevention of the intermediate syndrome, it has to be administered in continuous infusion, with permanent evaluation of the muscarinic syndrome. Toxogonin, a cholinesterase reactivator must be administered before aging appears and should not be used in carbamate poisoning because induces cerebral damage.

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Implications of communication style in the doctor-patient relationship

Pasca Maria Dorina
Abstract: The existence of a communication style between doctor and patient represents a modality of superior coding and decoding of the message delivered to the receptor thus the emitter has the certainty of understanding the transmitted information, the resultant being the basis of a special relationship between the two actors whose demarche represents a constructive sequence in the medical act. In this context the stile of communication sine-qua-non represents the key of communication simultaneously beginning from the structure and correlation of the five `Ws`, so the communication in doctor-patient relationship is an efficient and beneficial one for both parties. Paraphrasing we could say: Let me know your style and I will tell you what kind of doctor you are for a correct, responsible and professional fundament of the communication parameters engaged in the relation with the patient, delimiting identities and personal structures developed in a specific temporal-spatial context.

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Case Report

Lyme disease - the trigger of dermatomyositis

Birlutiu Victoria, Birlutiu R.M.
Abstract: Dermatomyositis, a myopathic inflammatory disease, characterized by specific skin lesions, with or without joint, esophageal or pulmonary involvement may have different infectious, viral, bacterial or parasitic triggers. We are presenting here the case of a patient suffering from the Lyme disease, whose evolution comprises a severe form of dermatomyositis.

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