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Volume XII, Number 2, 2008 - Therapeutics Pharmacology and Clinical Toxicology

Review


Farmacogenetica - utilitatea practica medicala

Adrian Streinu-Cercel
Abstract: Farmacogenetica studiaza varietatile de raspuns fata de medicamente in plan individual ca rezultat al diferentelor structurale individuale ale DNA-ului uman1. In acest context raspunsul la terapie ce include in termenii consacrati farmacocinetica drogului, eficacitatea, siguranta, si/sau tolerabilitatea va trebui sa ia in calcul si elementele de farmacogenetica care vor identifica cel mai bun medicament ce se potriveste unui pacient sau grup populational in functie de genotipul fiecaruia.

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Pharmacodynamic and therapeutic effects of antipsychotics

V.A. Voicu, F. Radulescu, M.D. Gheorghe
Abstract: The authors present in synthesis the antipsychotics mechanisms consecutive to the interaction with neurotransmission systems receptors, respectively the dopaminergic, serotoninergic, cholinergic system etc. Implicitly, a brief review is performed, by means of the pharmacological proofs of schizophrenia pathogenic theories. Another domain approached hints the ethio-pathogenic aspects of schizophrenia as the background of potential pharmacological targets - genetic components and impact of the factors perturbing the neurodevelopment and neurodegeneration processes initiated in a favorable context. The antipsychotics effects at the level of receptors and therapeutic effects correlations are analyzed on one side, which can be the direct consequence of action on receptor or indirect, consecutive to counterregulations determined in other neuromediation systems, and on the other side these effects can be relatively immediate (of hours - days order) or slowly installed (weeks) or do not appear at all (resistance to treatment, non-responders etc.). In this context two concepts are brought into discussion: the therapeutic effects with immediate onset and defined after 2-3 weeks and slow effects becoming marked after around one month and defined or not after few months. Another type of arguments are also brought into discussion: the slow and late effects of antidepressant, the addiction phenomenon installation as a complex process of neuroadaptation, but also the experimental and clinical proofs that the antipsychotics induce complex phenomenon on the cerebral structures. In fact in the context of chronic treatment with antipsychotics, the brain also behave following the known rules: it launches short latency, rapid processes with homeostatic destiny and initiating a series of other, more slow reactions implying protein and receptor synthesis, synaptic plasticity, neuroplasticity, neurogenesis etc. These processes implying the changes of some genes expression are approached as epigenetic phenomenon conferring to the organism, on one side, flexibility and adaptability and, on the other side, the genetic stability. In this context, the authors are appreciating that there are some convincingly arguments (direct or indirect) in order to admit that the antipsychotic - pathogenic psychotic processes interaction suppose two successive interdependent and correlated phases: the pharmacodynamic phase in which the active compound determines the known effects consecutive to antagonizing or activation of receptors for which it has affinity and the pharmacotherapeutic phase implying more slow complex processes. The rapid counter-regulations of the interconnected neurotransmission systems are part of the phenomenon probably initiating slower and more complex reactions implying compensatory phenomenon in a positive or negative sense (up or down-regulation) at the level of receptors, neuromediators synthesis, synaptic connections or even appearance of new neurons in some cerebral regions. This second phase will outline the final therapeutic response which will install in weeks or months and in connection with the rearrangement and resetting between different neurotransmission systems (affected in the schizophrenia context) on the basis of the presented epigenetic processes, we will report or not an individual therapeutic effect.

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New trends in the pharmacogenomics of antiretroviral therapy

L. Negrutiu
Abstract: Recent developments in the pharmacogenomics of antiretroviral drugs provide new prospects for predicting the efficacy of antiretroviral therapy and potential adverse effects. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be quantified and certain adverse effects can be assessed with validated measures. Additionally, there is increasing knowledge of the pharmacokinetics and dynamics of antiretroviral drugs, and some candidate genes implicated in the metabolism, transport and adverse effects have been identified. This article reviews the recently published work and summarizes the state of research in this area.

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Blood culture - actual requirements and perspectives

Olga Mihaela Dorobat, Al. Rafila
Abstract: The detection of bloodstream infections (BSI) is one of the most important tasks performed in clinical microbiology laboratory. Rapid and reliable detection of BSI includes identification of pathogens at species level and determination of antibiotic susceptibility patterns which are crucial because: patients can be treated with appropriate antimicrobial agents; the prognosis of the patient can be improved and the acquisition of resistance of the pathogen may be reduced; overall hospital costs for medical care will be reduced. Considerable efforts have been made to develop rapid, sensitive and specific assays for the detection of causative organism. Current automated continuous monitoring blood-culture systems permit a more rapid detection of bacteremia and fungemia comparative with manual methods. An overnight agar medium subculture from positive blood-culture bottle is the initial step for identification and antimicrobial susceptibility testing (AST) of pathogens causing bacteremia. This conventional culture method is time-consuming and several days are usually needed for microbial recovery, identification and AST. Automated systems for the identification and AST are able to generate accurate results in 2 to 12 h. Direct identification from positive blood-culture bottles in automated systems showed a variable correlation rate compared with standard method (31 to 96%). Direct AST performed from positive blood-culture bottles, using automated systems, like Phoenix, VITEK and VITEK 2, Sensititre, MicroScan and MICRONAUT, with a pre-determined dilution protocol, provides accurate results for most organism-antibiotic combination. New techniques have been introduced in last years for early diagnostic of bacterial infections by identifying bacterial genome. Rapid identification (4-5h) by new Genotyping technology (DNA strip) is now possible for many species of Gram negative rods and Gram positive bacteria together with the determination of methicillin, penicillin, vancomycin, erythromycin and aminoglycoside resistance. rRNA assay in blood cultures is highly sensitive (100%) and specific (96%). Real time PCR for nuc gene encoding nuclease and mec A gene encoding for methicillin resistance from blood-culture bottles yields a rapid identification (2-3h) of S. aureus and coagulase-negative staphylococci, including those methicillin-resistant.

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The reaction of human organism in the context of global warming pathophysiology of thermoregulation

Daniela Adriana Ion, Laura Ioana Chivu, R. D. Chivu, Octavia Raduta, Alina Fanea
Abstract: Recent worldwide evaluation of climate dynamics has demonstrated a 0,65o C increase in Earth surface mean temperature over the last 50 years (UNs Intergovernmental Committee for Climate Changes, 2007) and a further 1.1 - 6.4o C increase is predicted for the next 100 years. A significant impact of global warming on public health has been demonstrated, mainly due to extreme temperature variations (floods, excessive drought), air pollution, and changes in epidemiological features of infectious diseases. Risks for human health are greater as the region affected by climate changes is more impaired socio-economically. Therefore, Romania is among the countries with risk related to climate changes. From the pathophysiological perspective, the few studies conducted show that the human body is capable to adapt to linear climate changes. Still, extreme phenomena (heat or cold waves) yield high morbidity and mortality among persons with reduced adaptation ability such as elders, children and those suffering from chronic diseases. Morbidity and mortality are subsequent to impairments of the thermal regulation mechanisms as the latter yield disturbances of the hidroelectrolitic and acid-base homeostasis: - dehydration with hypovolemia and hyponatremia from exposure to high temperature; - diarrhoea with hypovolemia and hyponatremia from foodborne infections (both floods and drought limit accessibility to potable/drinking water); - hypoxia with acidosis in heat shock etc. Since all disturbances of the hydroelectrolytic and acid-base homeostasis can lead to negative consequences for the central nervous system, knowledge of these phenomena is essential both for diagnosing complications and especially for therapy, as inadequate measures in order to correct these disturbances can lead to permanent neurological injuries.

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The oxidative stress impact on the brain aging

T. Papacocea, Raluca Papacocea, Anca Badarau, Magda Buraga, Catalina Ciornei, A. Papacocea, Irina Stoian
Abstract: The brain aging is a complex process with anatomical, chemical and functional impact. The structural changes are not homogenonous and are related with engenous and exogenous factors. Brain aging is influenced by the oxidative stress, acting on serie of genes; the most important are related with growth hormon, histocompatibility proteins and apolipoproiein E control. Another important role in aging belongs to mitocondrial DNA, whose injuries generated by the free radicals action, increase with age in all body cells and in neurons. The mithocondrial DNA mutations accumulation seems to be a major factor in aging process. The mutations induced by the increasing of the free oxygen radicals concentration also increase with age. The psychological stress represents an important trigger for the oxydative stress induction in brain, for the reshaping of the regulatory brain structures involved in the long term emotional behavior control and for the acceleration of the brain aging. At cellular level, free oxygen radicals modulates a variety of intracellular signals, accelerating the mithosis and leading to early cellular senescence. Due to the imbalance between prooxidant and protective, antioxidant factors, proteic, lipidic and nucleic acids injuries appear. The interference between the free oxygen radicals and sinthesis, releasing and action of certain neurotrophic factors (BDNF- brain derived neurotrophic factor, NGF-nerve growth factoe, neurotensins, FGF- fibroblast growth factor, GDNF-glial derived growth factor) is reflected by the survival changes of specific populations of neurons. The impact on oxidative stress on neurogenesis was also analyzed. Neurogenesis is still present, but reduced in aging brain. The neurogenesis stimulation by factors which control it, represents not only a theorethical possibility but receives practical valences, as is reflected by the newest studies.

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Endogenous cannabinoid system. pharmacological implications, pharmacotherapeutical perspectives and the new drugs

Aurelia Nicoleta Cristea, B. S. Velescu
Abstract: This paper represents a review of the up-to-date knowledge about endogenous cannabinoid system (SCBE): pharmacological implications correlated with mechanism type (agonist, antagonist, endocannabinoid metabolize catalyzing enzymatic systems inhibitor), pharmacotherapeutic perspectives, as well as the new drugs with mechanisms on this system (rimonabant, nabilona, dronabinol), from pharmacological and therapeutical view point. New data on SCBE, opened a new possible view for the treatment of some nervous disorders (melancholic depression, epilepsy, neurodegenerative disorders as Parkinson and Alzheimer diseases), immune disorders (multiple sclerosis, Crohn´s disease), cardiovascular disorders (stroke, arterial hypertension, myocardial infarction), neuropathic pain, inflammation and cancer of immune origin. In a previous paper of this journal, the receptors, endocannabinoids, physiological functions, pathological implications and correlations with other signaling systems were presented.

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Septic coagulopathy

Ioana Iovanescu, Ioana Robitu, Elisabeta Balaita, C. Apostolescu, Cleo Rosculet, Monica Ivan
Abstract: Sepsis is an infection-induced inflammatory syndrome that results in a complex network of adaptive and maladaptive alterations in homeostatic mechanisms. Severe sepsis, defined as sepsis associated with acute organ failure, is a serious disease with a mortality rate of 30-50%. The coagulation system, through complex interactions, has an important role in the final outcome of the sepsis-induced inflammatory cascade. A fine and delicate balance that normally exists between anticoagulant mechanisms and the procoagulant response is altered in sepsis. Evidence suggesting that activation of the coagulation system may contribute to sepsis-related morbidity and mortality has led to extensive research attempting to correct the hemostatic defects seen in septic patients.

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Effectiveness of risedronate on fracture risk in postmenopausal osteoporosis

Diana Paun
Abstract: Osteoporosis is a skeletal disorder in which bone strength is compromised due to loss of bone density and bone quality. Osteoporosis is the most commonly occuring bone disease, and it is anticipated that the prevalence of osteoporosis will increase as the women population ages with a consequent increase in fracture risk. Risedronate have demonstrated efficacy in reducing the incidence of vertebral and non-vertebral fractures. Risedronate has been proven to provide fast and sustained vertebral and nonvertebral fracture reduction in postmenopausal women with established osteoporosis.

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Original Papers


Molecular modeling interaction of Sterically Stabilized Liposome

A. Neamtu, O. C. Mungiu
Abstract: The central phenomenon which plays a negative role in the therapeutic success of liposomal drug delivery formulations administered i.v. is the opsonization of transporters surface. This interaction reduces the circulation times of liposomes loaded with drugs by promoting their clearance from blood. Although there is a great amount of experimental results regarding the opsonization effect, there is much less understanding of the intimate molecular mechanisms of protein (opsonin) - liposome surface interactions. The aim of this second part of the study is to develop a methodology for the analysis of Sterically Stabilized Liposome (SSL) - opsonin interactions using molecular modeling techniques. We developed, using the previously validated model for liposomes (Neamtu, 2006), a method for predicting the shielding capabilities of SSL liposomes with respect to their physical and chemical surface properties.. Consequently we applied it to three varieties of pegilated liposomes which differ in the surface coverage densities and in the molecular mass of the polymer used. The method proved itself sensible enough to point out significant differences between the liposomes subjected to analysis. Finally, the liposomes with low coverage densities but with high polyethylenglicol molecular mass and especially mixed coverage liposomes proved the best shielding capabilities.

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Acute infection with ECHO 4 virus to children

Gh. Jugulete, Monica Luminos, Ruxandra Mantescu, Rozina Iagaru, Dorina Duma, Georgeta Constantinescu, Elena Gheorghe, Anca Draganescu, Roxana Matei, Angelica Visan, Adina Stancescu, Rodica Bacruban, Mihaela Iosipenco, Ana Ioana Persu
Abstract: Echoviral infection in children are frequently asymptomatic, more than 90 % infections are inapparent or undifferentiated febrile illnesses. Although there are 34 identified echoviral type who has been associated: undifferentiated febrile illnesses, febrile syndrome with: exanthema, respiratory manifestations, acute hemorrhagic conjunctivitis, myocarditis, hepatitis, gastrointestinal manifestations and neurological manifestations. In our study we have monitories the acute echoviral infection in children, hospitalized in National Institute of Infection Diseases Prof. dr. Matei Bals during 10.04.2007-10.05.2007. All cases live in Barbulesti, district Ialomita. The cases are classified after clinical manifestations in febrile syndrome with: exanthema, neurotically and digestive manifestations. In suspect cases of acute enteroviruse infection we have monitories: the age, sex and clinical manifestations. For established etiology of infection we have laboratory tests: serologic, cerebrospinal fluid, pharyngitis exudates and stool. During April-May 2007 admitted in our clinic 54 children with acute echoviral infection, serotype 4 and all cases have similar residence. The distribution on sex was roughly similar; more cases have age 4-7 years old (38.8%). Clinically, more frequent disease was febrile syndrome with neurological manifestations (50%) and digestive manifestations (24%). The evolution was favorable in every case; we not registered deceases and severe complications. The epidemic during April-May, 2007 in children who live in Barbulesti district Ialomita have etiology: ECHO virus type 4. Greater frequency was febrile disease associate with neurological and gastrointestinal manifestations. We not registered deceases and severe complications.

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Dermatofites onicomicosys

Adriana Turculeanu, Maria Balasoiu, Carmen Avramescu, Anca Ungureanu, Doina Olaru
Abstract: The nails, as annexes of the skin, can be the origin of various fungous affections, which, even though they are not too serious from a clinical point of view, provoke nuisance from an esthetic point of view and on a social plan. In this etiologic spectrum we can find dermatifitys as well. In this study, we will research the implications of dermatofitys in nail pathology on a group of 40 patients, suspects from a clinical point of view of suffering from dermatofitys onicomicosys. Of the 40 biological samples studies, 36 were pozitive for Trichophytonverrucosum and 4 for Candida albicans. The spectrum of chemical sensitivity for Trichophyton verrucosum was: sensitive at: Nistatin (36), Amphotericina B (36), Ketoconazol (36), Econazol (36), Flucytosine (29), Fluconazol (29), Miconazol (26); moderately sensitive at: Miconazol (10); rezistent at: Flucytosine (7), Fluconazol (7).

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Heatstroke and Heat Exhaustion Hot Weather Associated Extreme Pathology

Mariana Homos, Violeta Melinte, Valentina Simion, Carmen Barbulescu, Cristina Calomfirescu, Adriana Motoc, E. Ceausu
Abstract: In Bucharest area (Baneasa), during 15-25 July 2007, there were officially recorded temperatures between 33-39ºC, with more than 90% relative humidity over. That maximized the addressability to emergency medical services, the risk for alteration of some chronic diseases and heat exhaustion occurrence. Objectives: The study consisted in emphasizing clinical and evolutive traits of heat exhaustion/ heat stroke diagnosed patients, being aware about some preexisting risk factors. Material and methods: We diagnosed heat exhaustion/ heat stroke on 24 subjects, during 22 of July and 9th of August, on the basis of axillary high temperature, excluding other infectious causes. Results: The patients were over 57 years old, ranging from 57 to 96 years old, and sex distribution was almost equivalent. Most of them were Bucharest residents, 18 were living in blocks of flats, with no air conditioning systems. Associated chronic diseases were hypertension (15), obesity (12), neurological diseases (11), and diabetes mellitus (4). Clinical manifestations consisted in fever (38,5-42ºC), important alteration of general status, anhydrosis (14). The biologic profile was composed by initial hyperglycemia, except those with diabetes, leukocytosis and/ or hyponatremia. The treatment consisted in physical cooling, antipyretics, antibiotics, parenteral hydratation, corticoids, in some cases dopamine, diazepam, even diuretics. Evolution was favorable for 10 patients only, the rest died one hour to 90 hours later, after admittance.

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Therapeutical Practice


The experience in hospital of infectious diseases Iasi in severe fungal infections at persons HIV noninfected

Andra Teodor, Laura Ghibu, Carmen Dorobat, D. Teodor, Codrina Bejan, V. Luca
Abstract: To evaluated clinical and ethyological aspects, diagnosis and treatment possibilities at patients hospitalised with severe fungal infections in Clinic of Infectious Diseases - Iasi. MATERIAL AND METHODS - Retrospectiv study between 2004 - 2007 included all patients with severe fungal infection admitted in Clinic of Infectious Diseases. RESULTS - 29 patients (median age - 65 years). Risk factors for invasive fungal infection were: associated clinical entities (neurological pathologies - 14, renal failure - 6, diabetis - 4, cirrosis - 3, respiratory conditions - 2, pancitopeny - 2) and medical procedures (urinary catheter - 19, central intravenous catheter - 3, hemodialysis - 3). Fungal species were isolated from uroculture - 19, hemoculture - 5, culture of tracheal aspirate - 5.The most frequent specie was Candida albicans - 18 cases. In 4 cases of sepsis, Candida was associated with S. aureus. Antifungal testing identified resistance at Flucitosine (1 case) and intermediary susceptibility at Itraconasol (1 case). Fluconasol was preffered in therapy - 17 cases. In evolution 6 deces. CONCLUSIONS - Severe fungal infection has an increasing incidence in our hospital in the same time with increasing risk. We didnt observe significant changes in ethiology and antifungal susceptibility.

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Severe sepsis to a female patient with MRSA

Cristina Popescu, Adriana Paise, Victoria Arama, Violeta Molagic, M. Chiotan, Argentina Petre, Georgeta Popa, M. Ionescu, Daniela Munteanu, Magda Parvu
Abstract: We present the case of a 50-years female patient with systemic lupus erythematosus with long-therm corticoid treatment who developed severe sepsis with methicillin resistant Stapylococcus aureus after a sternocleidomastoidian abcess. She was treated for two months but ten days after the antibiotic therapy was stopped, the patient complained about sever back pain and the vertebral radiography was suggestive for staphylococcal spondilodiscitis, although there was no sign of bone infection before. She received four months of antibiotic therapy. After 30 days of favourable outcome, the patient was transffered to an orthopaedic hospital for surgical intervention. The patient have continued the antibiotic treatment in our clinic, with favourable response. This case proves the importance of bone scintigrapy in the screening of septic metastasis in staphilococcal systemic infections.

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Strategy and clinically management of dyslipidemia from HIV infection

S. Rugina, Irina Magdalena Dumitru
Abstract: Highly active antiretroviral therapy (HAART) has lead to a dramatic decrease in the mortality of patients infected with HIV. However, metabolic side effects, including lipodystrophy and dyslipidemia, have been reported in patients treated with antiretroviral therapy (HAART). Challenges to more successful HIV therapy include improving adherence to drugs by enhancing their pharmacological and toxicity profiles.

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The Disseminated Kaposi Sarcoma

Victoria Birlutiu, Mirela Mitrea
Abstract: Kaposi sarcoma, a vascular proliferate malignant disease (a malignant, multi-focal systemic disease that originates from the vascular endothelium), associated with the HIV infection is widely witnessed in drug users that administrate it by intravenous injection, in women, or hemophiliacs. The drop of CD4 cells below 200/mm3 may determine the spreading of the Kaposis sarcoma to skin, but also to colon, lungs, genital organs, lymphatic system. The treatment for the common injuries includes chemotherapy, radiotherapy, surgical treatment, local administration of cytostatics (vinblastina), retinoids -like Alitretinoin gel. More extensive forms of the disease require a general cytostatic treatment (such as bleomycin, etoposide, vinblastine, vincristine), liposomal forms of anthracyclines (such as pegylated liposomal doxorubicin or daunorubicin), paclitaxel, Imatinib, interferon, interferon in association with cytostatics, isotretinoin, cytokine inhibitors, HCG (human chorionic gonadotropin). We hereby present the case of M.T., a 41 years old male patient, infected with HIV since 2002, with no HAART therapy, presenting antecedents of pulmonary tuberculosis, gonorrhea, malignant syphilis (lues maligna), who developed Kaposi sarcoma disease affecting the skin, oral mucus, lung, genital organs, with values of CD4 ranging over 200/mm3 , with a good clinical evolution after initiating the HAART therapy, associated with the systemic chemotherapy

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Candidal endocarditis

Brindusa Tilea, Carmen Chiriac, I. Tilea, H. Suciu, Anca Georgescu, Cristina Garbovan
Abstract: Candidal endocarditis is an inflammatory and proliferative disease of the endocardium that mainly affects valvular structures. Fungal aetiology is uncommon and appears less frequently when vegetation appears on native valves. We present a case of native mitral valve fungal endocarditis in a patient with no apparent risk factors with a history of infectious syndrome. Laboratory findings revealed blood cultures positive for Candida albicans and transthoracic echocardiography revealed an oscillating mass over posterior mitral leaflet. During adequate antifungal therapy, case evolution was slowly favourable; when haemodynamic status was stable the patient underwent mitral valve replacement. Pathologic exam confirmed diagnosis. Fungal endocarditis is a serious disease associated with a high mortality and whenever the diagnosis is suspected, antifungal therapy must be started and appropriate surgery (prosthetic valve replacement) should be considered.

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Tricuspidal staphylococcal endocarditis

Irina Niculescu, A. Cupsa, I. Diaconescu, L. Giubelan, Florentina Dumitrescu, Manuela Musa, Stefania Ionescu
Abstract: Infective endocarditis (IE), relatively uncommon disease could have a clinical presentation of sepsis and could be a clinical and therapeutic challenge. The tricuspid valve rarely is involved and audible heart murmurs may be absent in this case. Case presentation: We present the case of a 59 previously healty male, who visits ER for fever, productive cough, dyspnea and feet edema. Insidious onset (6 to 7 weeks previously) with asthenia, fever (started 1 to 2 weeks after the onset) Ten days later the patient (Px) becomes unconscious. Clinically: fever, palor, productive cough, polypnea, signs of right basal pneumonia, tachycardia (but no murmurs), feet edema, liver and spleen enlargements, lumbar pain and functio laesa of the left foot. Biologically: anemia, mild leukocytosis with 77% neutrophiles, increased ESR (107/120 mm/h), CRP detected in serum, 3 blood culture positive for Staphylococcus aureus. X-rays shows pneumonia. Treatment with Linesolid has no benefit. Examination of the heart using Doppler ultrasound reveals a tricuspidal 12 mm (then 18 mm) upgrowth. Vancomycin is the second choice for an antibiotic and then Oxacilin and the fever vanishes, blood cultures becomes negatives and clinical signs attenuates. Ten days after discharge Px underwent cardiac surgery for valvular prosthesis implant. Discussion: sepsis has been the foreground for a mute tricuspidal IE due to S. aureus, emerged in a normal host, representing a diagnostic riddle, as well as challenging the clinician about antibiotic options and case management.

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Sepsis with Clostridium in a child - case presentation

Claudia Simona Cambrea, Ioana Cretu-Stancu, Claudia Nina Rugina
Abstract: Clostridia are anaerobic spore forming bacilli, which are responsible of different diseases: gas gangrene and related wound infection (C. Perfringens, C. Novyi, C. Septicum and others), tetanus (C. tetani), botulism (C. botulinum), antibiotic associated diarrhea and pseudomembranous colitis (C. difficile). Most of these microorganisms produce exotoxins that play an important role in the pathogenesis of the diseases. Objective: To present a case of sepsis with Clostridium spp in a 2 years old child. Results: A male child aged 2 years old, from urban area was hospitalised in our clinic with bad general state for fever, dispneea, polipneea, apathy, pallor, frequent diarrheic stools. After endovenous and oral hydroelectrolytic addition and antibiotic treatment with Ceftriaxon 1g/day + Gentamycine 60mg/day for 4 days bad general state persisted as well as fever and diarrheic stools, respiratory symptoms accentuated, and tachycardia appeared. Blood culture taken in the first 48h of hospitalisation evidenced presence of a Gram+ anaerobic spore forming bacilli - Clostridium spp. We introduce treatment with Imipenem/cillastatin 170mg/6h + Amikacine 200mg/day +Metronidazol 300mg/day for 14 days and then Fortum 1,5g/day + Ciprofloxacine 250mg/ day for another 12 days with a slowly favourable evolution. Conclusions: Although it is a rare disease in children, sepsis with Clostridium spp in children should be taken into consideration in clinical and epidemiological background. Evolution of sepsis with Clostridium spp could be unfavourable in case of inadequate therapy.

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Nonpharmacologic interventions in osteoporosis therapy

Diana Paun, Alina Sucaliuc, Rodica Petris, Carmen Ene, C. Dumitrache
Abstract: Osteoporosis is widespread and is associated with risk of fragility fractures. The prevalence of osteoporosis increses with age in men and women and current demographic trends show a greatly incresing number of persons at risk. Many risk factors for low bone mass and fracture have been identified and afford opportunities for intervention before fracture occurs. Nonpharmacologic interventions are important variables in the management of osteoporosis. These measures as a prelude to or in conjunction with pharmacotherapy can be extremely beneficial for improving skeletal health. Adequate nutrition and exercise play a major role in the prevention and treatment of osteoporosis, particulary in elderly individuals.

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