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Volume XIII, Number 4, 2009 - Therapeutics Pharmacology and Clinical Toxicology


State-of-Art - Dynamics of A/H1N1 pandemic virus infection in Romania - therapeutic implications

A. Streinu-Cercel, Adriana Pistol, Rodica Bacruban, D. Otelea, Daniela Pitigoi, Anca Streinu-Cercel, C. Apostolescu, Arina Balaita, Doina Iovanescu, Amalia Canton, Fl. Popovici Simona Paraschiv
Abstract: A comparative analysis of the 3 types of influenza viruses - pandemic, seasonal and avian (H5N1) - revealed considerable discrepancies in defining risk groups, types of clinical onset and attack and lethality rates. Processing the lessons learned from past influenza epidemics and from the H5N1 infection, the medical world developed action blueprints for the eventuality of pandemic focused on reducing the death rate calculated according to the lethality index. A continual calculation of the fatality rate lead to noteworthy changes in the management of the A/H1N1v infected case, changes regarding the decision to hospitalize and the length of the specific therapy. A strict surveillance of the clinical cases and of the respective contacts substantially contributed to limiting the circulation of this new A/H1N1v virus over the summer and over the beginning of autumn. Epidemiological and clinical evaluation of the viral dynamics is crucial to the management of the current pandemic.

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Chronic fatigue syndrome - a not yet fully understood entity

Ioana Cristina Amihaesei, O.C. Mungiu
Abstract: The chronic fatigue syndrome (CFS) is characterized by an intense fatigue state, which is not relieved by bed rest, has duration of at least 6 months and is responsible for impairment of the subjects capacity of fulfilling daily activities. The diagnosis is difficult because besides fatigue, the syndrome associates symptoms common for many other diseases, such as - muscle pain, memory and concentration disorders, headaches, multiple joint pain, sleep disorders, tender lymph nodes. The causes are unknown; the syndrome affects more often the female sex, during the fourth and fifth decades of life. Usually it lasts for years. An important feature is represented by worsening of the symptoms after intense physical or mental activity, lasting for more than 24 hours. Although this does not cover the whole polymorphism of the syndrome, in 1994 two diagnostic criteria were established: 1. extreme fatigue, lasting for at least 6 months, without other medical condition; 2. at least 4 of the following symptoms: severe impairment of short term memory and/or of the concentration capacity; muscle pain; multiple joint pain; sore throat; unresting sleep; headaches displaying a new pattern or severity; tender lymph nodes; post-exertional fatigue, lasting more than 24 hours. More than one million people were diagnosed with the syndrome in the USA, but tens of millions of people have similar syndromes, without fully satisfying the diagnosis criteria. It is estimated that only 20% of the cases are diagnosed. CFS may be as disabling as multiple sclerosis, lupus, rheumatoid arthritis, congestive heart failure, etc. Although a cause hasnt been isolated yet, possible etiologies include viral infections, stress and exposure to toxins. Immune data did not reveal immune factors involved in the genesis of the syndrome, besides a predisposition to developing allergic reactions. The hypothalamus-pituitary-adrenal axis showed no changes useful for diagnosis or therapy. Overlapping CFS and neurally mediated hypotension were investigated with no results in treating all cases. The syndrome shows a cyclic evolution with remission and relapse periods. After the apparent recovery, a relapse is usual. The earlier the diagnosis and therapy initiation, the better the chances of full and rapid recovery. The therapy targets each patients symptoms - pain, sleep disorders, memory and concentration problems. Many patients may overreact to medication, especially to sedatives. Usually, the therapeutic benefits are obtained with lower doses than usual. The medications side effects may aggravate the symptoms of the syndrome. The patients usually display high sensitivity to caffeine, alcohol and nicotine. Alternative therapies, such as acupuncture, massage, yoga are used for relieving the symptoms. There is need for more studies focused on the causes of the chronic fatigue syndrome.

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Original Papers

Post-operative bacterial meningitis. a retrospective study of 68 cases hospitalised in the Infectious Diseases Clinic of Iasi, between 2004 - 2008

Codrina Bejan, Carmen Manciuc, G. Dorobat, Laura Ghibu Carmen Dorobat
Abstract: There is no standard definition of meningitis occurring post neurosurgical intervention. The diagnosis of the disease is difficult because of the high-frequency meningeal reactions in the context of preexisting symptoms that mask the signs and symptoms of meningitis. Cerebrospinal fluid examination is the standard for diagnosis. Material and methods Clinical and laboratory data were studied, as well as pre and post-antibiotherapy developments of case report forms of 68 patients with post- operative meningitis, hospitalized in the Clinic of Infectious Diseases, Iasi, between 2004-2008. Objective. We designed a retrospective evaluation of patients with post-operative meningitis in terms of CSF parameters, etiologic spectrum, inflammatory syndrome, clinical signs and symptoms, fever span, duration of hospitalization. The statistics (`T student` test and Confidence Interval) supported the evolution of the patients under study. Conclusions. 1. The etiologic agent most frequently involved was Staphylococcus meti-R, consistent with field literature. 2. The first line therapeutic option, according to the our services experience, in line with the arguments of the present study: third-generation cephalosporins + fluoroquinolones / carbapenems + fluoroquinolones.

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Late presentation and limited transmitted drug resistance in newly diagnosed HIV-1 patients from the North-Eastern region of Romania

D. Florea, Simona Paraschiv, Mihaela Fratila, L. Prisacaru, Cristina Nicolau, Irina Teodorescu, Elena Duca, Carmen Dorobat, D. Otelea
Abstract: To evaluate the prevalence of resistance mutations in antiretroviral (ARV) treatment-naive patients from the north-eastern region of Romania. Methods. Adult patients from the HIV/AIDS Regional Centre of Iasi were investigated between January 2007 and June 2008. HIV genotyping was performed by using the ViroSeq Genotyping System. The prevalence of transmitted resistance was calculated by using the WHO recommended list of mutations. Results. Fifty patients were included in the study. Most of them were late presenters, 56% had AIDS. Subtype F1 predominated, although other subtypes (B, C and CRF02_AG) were detected. A statistical significant association between older patients, risk-related behaviour and non-F1 subtype infection was found. In the 41 HIV sequences analyzed, only two resistance related mutations were detected: T215S (2 cases) and K103N (1 case). Conclusions. The transmitted HIV resistance has low prevalence and is limited to single NRTI and NNRTI resistance mutations. These results might be influenced by the large proportion of late presenters in the studied group, with a much higher prevalence in recently infected cases.

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New strategies for the treatment of tuberculosis

Victoria Birlutiu, Mirela Mitrea
Abstract: The treatment of Tuberculosis may be associated with an emergence of mycobacterial resistance through chromosomal alterations, but also through a poor administration of treatment, leading to the emergence of multi-drug-resistant strains MDR-TB or extensively drug-resistant, XDR-TB, responsible for over one million illnesses. We aim at presenting current WHO recommendations for patients in treatment failure as well as information regarding the new compounds: TMC-207, OPC-67683, PA-824, LL-3858 and SQ-109, currently being evaluated in the treatment of tuberculosis.

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MDR1 gene polymorphism and refractory epilepsy

Anca Dana Buzoianu, Octavia Sabin, Corina Ioana Bocsan, Claudia Militaru
Abstract: One of the currently studied hypotheses concerning the resistance to the treatment of epilepsy is the overexpression of efflux transporters such as P-glycoprotein at the intestinal and blood-brain barrier that prevents achieving an optimal drug concentration in the brain. MDR1 gene variations affect the expression and function of P-gp, as demonstrated by the association between ABCB1 gene polymorphism and the risk of drug-resistance in patients with lymphoproliferative disorders. P-gp is a major determining factor for the availability and effect of in vivo drugs and is involved in drug interactions that may become clinically relevant, such as the variability between the absorption and biodistribution of carbamazepine and phenytoin. There are few studies on refractory epilepsy, with contradictory results and conducted on different ethnic populations. The introduction of pharmacogenetic studies in medical practice, with the purpose of better prescribing antiepileptics and reducing refractory cases requires strong evidence to support investigations such as genotyping.

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Antibiotherapy control program - functionality assessment

Ramona Ionescu, D. Grigorescu, Gh. Pamfil
Abstract: Antibiotic Control Programs were recommended by World Health Organization in order to minimize microbial resistance, provide the best therapy for patients, at the lowest costs for the healthcare institutions. We assessed the functionality of the Antibiotic Control Program in the Emergency County Hospital Brasov, over a period of two years (2004 - 2005). Method. This is a prospective descriptive study, based on the consults data, computed as daily entries into an excel table, by the infectious diseases specialist. Results. 670 infectious diseases consults were performed. 89% of the requests for therapy were for prescription of common antibiotics; approval of a restricted antibiotic represented 64% of the requests (p=0,0001). The direct communication between the physicians and the infectious diseases specialist was very good in 60% of the cases. This was significantly better with hematologists (82%) and internists (68%) than with intensivists (51%) or surgeons (51%); p<0,05. The adherence to the recommendations of the infectious diseases specialist was of 88%, 93% in the internal medicine department and 83% in the intensive care unit (p<0,05). The incidence of nosocomial infections was 26%. In 93 of the 124 patients (75%) with nosocomial infections, therapy with a restricted antibiotic was prescribed, but 17 of the patients died (14%). All of these patients benefited from therapy with at least one of the new antibiotics. Conclusions. The Antibiotherapy Control Program proved to be functioning successfully, in spite of the implementation difficulties in ICU and surgery. The program did in no way obstruct administration of ACP restricted antibiotics to patients with nosocomial infections.

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Bivalent cations in oral pathology

Elena Luca, M. Nechifor
Abstract: Bivalent cations have multiple actions in the oro-maxillary region. In patients with oro-maxillary area suppurations, our data revealed significant increase in the salivary magnesium concentration and a decrease in the serum zinc concentration. In maxillary sinusitis, there are no changes in the calcium and magnesium concentrations, whereas the plasmatic zinc level is decreased. Zn, Cu, Ca, Mg also play important roles in the synthesis of dental enamel, and their misbalances are involved in the pathogeny of tooth decay and other maxillary diseases

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Therapeutical Practice

Clinical epidemiology of HIV-tuberculosis coinfection

Manuela Arbune, Otilia Benea, C. Scorpan
Abstract: HIV screening of tuberculosis patients has been a common practice in Romania, since 1998. Compared to the national statistics, the Galati county has similar prevalence of HIV/AIDS but higher prevalence of TB. The study is a retrospective analytic study assessing the epidemiology and clinical characteristics of HIV tuberculosis coinfection in Galati during 1998-2008. A number of 98 cases of HIV/TB were recorded out of the total 324 HIV cases. The average annual incidence of tuberculosis was over 30 times higher in HIV positive patients (5.2%) than in HIV negative ones and it displayed a tendency of increasing. HIV was acquired vertically (11%), sexually (19%) or horizontally during early childhood (70%). 44% of the patients had tuberculosis as the primary AIDS defining event, while 26.5% developed tuberculosis after HIV diagnosis. 45% of the cases had extra-pulmonary tuberculosis involvement and correlated with lower CD4 count, older age and mortality rate. 50% had microbiological criteria for tuberculosis diagnosis. The rate of microbiological evidence was lower in the primary pulmonary tuberculosis than in the secondary one and correlated with younger age. 27% of the patients received antiretroviral treatment (ARV) at the time of tuberculosis diagnosis and 2 developed tuberculosis as immune reconstruction event. Out of 98 HIV/ tuberculosis patients, 67 were cured, 11 relapsed and 21 died. The risk of death is related to the severity of the immunosuppression at the time of tuberculosis diagnosis (median CD4 count of 219 in survivors vs. 42 in the case of deceased patients, p< 0.001). The risk factors for death in HIV/ tuberculosis co-infection are low CD4, extra-pulmonary involvement and older age. A new strategy for the improvement of tuberculosis diagnosis in HIV patients should allow earlier medical involvement in order to decrease the HIV- tuberculosis mortality in Galati - Romania.

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Difficult to treat patients with HBeAg negative Chronic B Hepatitis

Manuela Curescu
Abstract: There are 2 billion people infected worldwide, with approximately 5% of the world`s population (or 350 million people) being carriers of chronic hepatitis B. [2] Worldwide, chronic hepatitis B is the 10th leading cause of death. HBeAg-negative chronic hepatitis B patients show a lower sustained response to interferon (IFN). Methods. We present two clinical cases of chronic HBeAg negative patients who received several treatments, from standard interferon alpha 2a to nucleoside analogues. Results. In a number of cases, the treatment of chronic HBeAg negative chronic hepatitis B can be a real challenge for the physicians and it is possible that prolonged Peginterferon therapy or addition of nucleot(s) ides analogues may increase the response rate.

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Toxic and drug-induced syncope in medical practice

Catalina Lionte
Abstract: The syncope is a symptom relatively commonly encountered in medical practice, often with dramatic consequences, with a risk of sudden death, which deserves thorough investigation and appropriate treatment of its cause, but its causes are difficult to diagnose. Consequently, syncope often leads to hospital admission, multiple consults and performing many diagnostic tests. The toxic-induced syncope was rarely reviewed in literature, as it comports a multidisciplinary approach. This paper provides information on toxic and drug-induced syncope, focusing on etiology and pathophysiology, as well as clinical and differential diagnosis, prognosis and treatment.

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The treatment of coarctation of the aorta in the newborn with heart failure

Aurora Iosefina Sima
Abstract: Coarctation of the aorta is a congenital heart defect, involving a narrowing of the descendingthoracic aorta (hemodynamically significant), most likely located distal from the left subclavian artery, at the origin of the arterial ligament. This article discusses the characteristics of the coarctation of the aorta in newborns and the treatment options.

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Case Report

The evolution of a vascular tumor with rapid metastasis in an HIV-infected young patient

C. Marcas, C. Cambrea, S. Rugina, M. Ilie, D. Tanase, I. Stancu Cretu, S. Diaconu, I. G. s¾erban, L. Vlahopol, E. A Caraveteanu, I. Ghiulendan
Abstract: Given the limited data on the effect of HAART on the natural history of certain malignant diseases, the therapeutic approach of an HIV-positive patient with neoplasia should be the same as that of an HIV-negative patient. Objectives. We present the case of a young HIV-positive patient with a vascular tumor with visceral metastases with fulminant onset and evolution. Case report. A 19 year-old patient with C3 stage HIV AIDS infection was urgently admitted for intense headache and sudden-onset convulsive seizures. A cerebral CT exam revealed multiple intracranial expansive processes. The patient abruptly developed flaccid paraplegia. An emergency MRI of the thoracolumbar vertebral spine was performed. The patient shortly deceased through altering of the neurologic status and through acute renal failure. An anatomopathologic exam revealed a vascular tumoral mass which compressed the cerebral hemispheres, with intense periosteal reaction. Similar disseminated tumors were identified in the liver, pancreas, kidney. Discussions. All HIV-positive patients with malignant diseases should undergo treatment with HAART combined with the standard oncologic therapy for the given malignant disease. The HIV-positive patients with tumors need to be offered access to the same kind of oncologic treatment as HIV-negative patients, ideally through interdisciplinary consults with infectious diseases physicians, with heightened attention to the possible interactions between chemotherapy and HAART.

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