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Volume XII, Number 3, 2008 - Therapeutics Pharmacology and Clinical Toxicology


PET CT imaging: current indications and usage for oncology in the United States of America

Andrei Iagaru
Abstract: Positron Emission Tomography (PET) has gained widespread acceptance for the diagnosis, staging, and management of a variety of malignancies. The fundamental strength of PET over conventional imaging is the ability to convey functional information that even the most exquisitely detailed anatomic image cannot provide. 18F FDG, the standard PET radiopharmaceutical in clinical use currently, is a glucose analog that is taken up by cells in proportion to their rate of glucose metabolism. The increased glycolytic rate and glucose avidity of malignant cells in comparison to normal tissue is the basis of the ability of 18F FDG PET imaging to accurately differentiate cancer from benign tissue regardless of morphology (80). Dual modality PET/CT increases patient convenience by permitting PET and CT imaging in a single appointment. But perhaps more importantly, initial studies indicate that the sum of the two modalities is better than either used separately. Despite the high costs associated with PET/CT scanning, significant savings are possible for the healthcare system due to avoidance of unnecessary surgeries (through accurate staging), selection of the appropriate therapy and early detection of cancer recurrence.

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HIV TAMS - Genotipic resistance in expansion

Lucian Negrutiu
Abstract: The introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease in HIV and AIDS-related mortality and morbidity. However, these treatments can select for drug-resistant viruses which are associated with poor virological responses to the antiretroviral therapy and possible loss of clinical benefit. Drug-resistant viruses can also be transmitted between individuals. In the absence of drug pressure, transmitted drug-resistant viruses gradually lose resistance mutations that confer a selective disadvantage as they evolve to more fit viruses.As a result, unusual resistance-related genotypes not commonly seen in treated patients may arise in the population. Viruses with unique patterns of thymidine analogue-associated mutations (TAMs) have been identified in a substantial proportion of treatment-naive recently diagnosed persons 35-38. In this leading article, we discuss these findings and the potential impact of these unique reverse transcriptase (RT) genotypes on evolution of resistance and treatment responses.

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Statins in the treatment of atherogenic dislipidemia

Mariana Radoi
Abstract: Statins are the most usefull drugs in the treatment of atherogenic dislipidemia. The benefit of statins was demonstrated in primary and secondary prevention of cardiovascular disease and consists in reduction of major cardiovascular events. The clinical benefit is associated with decreasing in LDL-c levels. New data seems to be needed to establish optimal LDL-c levels in secondary prevention. The benefit is greater and with cost-efficiency in high cardiovascular risk patients. When used in moderate dosage statins are well tolerated drugs but high statins therapeutic regimen is associated with enhanced risk in increasing of liver enzymes levels.

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The role of N Methyl D Aspartate receptors in the psychopharmacology of mood disorders

D. Vasile, O. Vasiliu, Mihaela Vasile, Oana Cretu
Abstract: The ethiology of mood disorders is not yet completely known and the high rates of conventional treatment resistant cases is consistent with this observation. The involvement of glutamate and NMDA receptors in the pathogenesis of mood disorders is based on consistent, yet not complete, experimental data. The preclinical experiments (behavioural animal models of depression) as well as pharmacological clinical data from trials with ketamine or lamotrigine support the glutamate hypothesis. New therapeutic perspectives could result from data analysis that support the role of glutamate in mood disorders.

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Management of CMV infection in renal transplant recipients

Cristina Cismaru, Doina Tatulescu, M. Lucan, Adriana Slavcovici
Abstract: CMV is an important pathogen in renal transplant recipients due to both direct and indirect effects. Infection presents most often as asymptomatic viremia or with fever and neutropenia - CMV syndrome. Indirect effects are: supressing of host defenses and predisposing to secondary infections with fungus and bacteria. Prevention must be individualized by risk group and immunosuppressive regimen. The standard therapy in CMV disease is with ganciclovir. Alternative therapies include foscarnet, cidofovir, leflunomide. The role of valganciclovir in treatment of invasive disease is on study

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Quantum medicine

R. Macovei1, Anna S. Ghiorghiu
Abstract: BRT is the therapy with electromagnetic oscillations, structures of the organism come into resonance with them. The influence is possible on cellular level as at the level of organ, system of organs and whole body. The main idea of applying resonance in medicine is that by correct selection of frequency and form of medicinal (electromagnetic) influence its possble to amplify normal (physiological) and attenuate pathological oscillation of the human body. So bioresonance influence could be directed both for neutralization of pathological and restoration of physiological oscillations disturbed during pathological oscillations.

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Original Papers

Efficacy of Darunavir Ritonavir in treatment-experienced HIV 1

Pozniak A, Jayaweera D, Hoy J, De Meyer S, De Paepe E, Spinosa-Guzman S
Abstract: Darunavir (DRV; TMC114) is a HIV protease inhibitor (PI) with potent activity against both wild-type and resistant HIV strains, including multidrug- and cross-resistant strains, and has a high genetic barrier to the development of resistance. The present study combined analysis of POWER 1 and 2 evaluated the efficacy of DRV/r 600/100mg bid compared with CPI(s) at Week 96. Methods: Patients were male or female, aged >18 years, with HIV-1 RNA >1,000 copies/mL and >1 primary PI mutation (D30N, M46I/L, G48V, I50V/L, V82A/F/T/S, I84V and L90M)9 at screening. Hepatitis B or C coinfected patients were included in POWER 1 if clinically stable and not requiring treatment, but such patients were excluded from POWER 2. The primary efficacy endpoint was confirmed viral load reduction >1.0 log10 copies/mL at Week 96 from baseline (time-to-loss of virological response [TLOVR] algorithm). The efficacy analysis was based on the intent-to-treat (ITT) population. The secondary efficacy endpoints were the proportion of patients reaching a viral load <50 copies/mL (TLOVR), change in viral load from baseline (non-completer=failure [NC=F] analysis) and change in CD4 cell count from baseline (last observation carried forward analysis [LOCF]). Conclusions: Treatment with DRV/r 600/100mg bid led to sustained virological and immunological responses in treatment-experienced patients with advanced HIV infection over 96 weeks. Patients receiving DRV/r 600/100mg bid had statistically significantly greater reductions in viral load and increases in CD4 cell count at Week 96 than patients receiving CPI(s) These results support and extend the findings of POWER 1 and 2 at both Weeks 24 and 48, confirming that DRV/r 600/100mg bid is a highly effective treatment option in treatment-experienced patients.

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ARTEMIS: Week 48 safety and efficacy of Darunavir/r by gender, age and race

Jaime Andrade-Villanueva, Gisela Herrera, Philippe Chiliade, Ben Van Baelen, Eric Lefebvre, Ludo Lavreys
Abstract: Once-daily DRV/r 800/100mg is being examined in ARTEMIS (TMC114-C211; AntiRetroviral Therapy with TMC114 Examined In Naive Subjects), an ongoing, open-label, Phase III study comparing the efficacy and safety of DRV/r versus lopinavir with low-dose ritonavir (LPV/r) in treatment-naive, HIV-1-infected adult patients. The aim of the present analysis was to determine the influence of gender, age and race on the safety and efficacy at Week 48 of patients receiving DRV/r 800/100mg qd in the ARTEMIS trial. Methods: All patients received a fixed background regimen of tenofovir disoproxil fumarate (TDF) 300mg qd and emtricitabine (FTC) 200mg qd. Safety and efficacy assessments were performed at screening, baseline, Week 2 and every 4 weeks until Week 16, at Week 24 and every 12 weeks thereafter. Results: No clinically meaningful differences were observed in the tolerability of DRV/r 800/100mg qd in treatment-naive patients at Week 48, irrespective of gender, age or race. The majority of AEs and laboratory abnormalities observed in all subgroups were of mild-to-moderate severity. These incidences were similar to those reported for the overall population and were infrequently associated with treatment discontinuation. The efficacy of DRV/r through Week 48 was similar across the subgroups, and was comparable to the overall population. DRV/r 800/100mg qd is an effective, well-tolerated once-daily treatment option for treatment-naive patients regardless of gender, age or race.

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Lipodystrophy syndrome to the children HIV infected

Manuela Arbune, Voichita Mogos, E. Zbranca, Cristina Cristea, M. Hutanu
Abstract: The present study evaluates the development of lipodystrophy syndrome (LDS) during 3 years, to 148 HIV infected children between 11 and 16 years old. They were treated with more antiretroviral (ARV) combinations. LDS was not found to any child under age 12, but has been developed by 41.5% children on media age of 14.7. 89% of LDS patients have experienced the puberty onset, but there is no correlation with a certain pubertal stage. The dyslipidemia is more frequent than LDS and they both are correlated with certain ARV. The severe baseline immunosupression and the eficiency of immune reconstruction after ARV are associated with LDS. Goiter was found to 62.5% patients with LDS but it is not clear either it is favoured by LDS or the goiter and LDS are independent manifestations of the immune reconstruction.

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Clinicals epidemiologicals and therapeutics features of patients with Acute Limphoblastic Leukemia in Hematology Clinic Timisoara

Violeta Todorescu, M. Gafencu, Hortensia Ionita
Abstract: Acute limphoblastic leukemia is a clonal neoplazic profileration of the progenitor limphoids stem cells characterized by their differentation stop and growth, the incidence of the disease being influenced by age, sex, ethnical, genetical factors, exposure to noxes. Objectives: The study aims to evaluate the incidence of leukemia evaluation to certain factors (age, sex, occurring environment, personal habits, exposure to noxes, pathological personal and family history) and the overall survival rate in accordance with therapy, for a period of ten years with the help of a retrospective epidemiological descriptive study. Material and method: The research was done in the Hematology Clinic Timisoara, started in 01.01.1996 and finished in 31.12.2005 - in the studied lot there were introduced newly diagnosticated patients in the clinic with acute limphoblastic leukemia. Evaluated factors were: age, sex, occurring environment, personal habits, exposure to noxes, pathological personal and family history, therapy, remission rate and the overall survival rate. The incidence of the disease is greater in the years 2002, 2005, 1997, 1999; the greatest frequency being at the age group under 20 years old, a second peak of the frequency curve being observed at the age 40 to 50 years old, and the variation of the leukemia incidence as far as the month of birth was concerned being statistically insignificant. The predominance of the male sex was noticed, a greater frequency of thedisease among the patients coming from the urban environment, a third of the patients being smokers, 19.29% of the patients are exposed to noxes, and 14.03% presenting pathological heterocolateral antecedents respectively personal pathological antecedents.

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The role of intraarterial chemotherapy in hepatic tumors

B. Popa, Monica Popiel, L. Gulie, C. Turculet, M. Beuran
Abstract: First transcatheter embolization of hepatic artery has been materializing in 1974, in France, for unresectable hepatic tumors. Then this treatment has become use enough in many countries, especially in Japan, where primary hepatic tumors are very frequent. In this article we will discuss the endovascular treatment procedures and the role of intraarterial chemotherapy in hepatic tumors, based on the experience and good collaboration between Angiography and Surgery departments of Clinical Emergency Hospital. A diagnostic arteriography was performed to patients selected to intraarterial chemotherapy in order to better visualize hepatic vascular pattern and the branches responsible for tumoral irrigation and to establish the most suitable treatment procedure: intraarterial chemoinfusion or chemoembolisation. Most of the patients have benefit by intraarterial hepatic chemoembolisation, selective chemoinfusion was the procedure selected to patients with contraindication for embolic materials or Lipiodol (cirrhosis-Child C, thrombosis of portal vein, hepatic insufficiency). For treatment of primary hepatic tumors we use 5-F-Uracil, Farmarubicin and Mytomicin C. Intraarterial hepatic chemotherapy prooved to be an effective alternative for unresectable tumours.

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Etiological study of bloodstream infections in INBI patients

Ioana Badicut, Smaranda Botea, Cristina Tenea, Monica Popoiu, Marcela Furtuna
Abstract: The bacteremic and septicemic risk conditions have increased over the last decades. The etiological spectrum of these nosological entities has greatly diversified, the classic pathogen occurrences have decreased and those of opportunistic microorganisms have increased; these microorganisms are very diversified and are a normal presence of the tegument, in the digestive system, saprophyte of air-microflora. The sensitivity spectrum to antibiotics has narrowed significantly with corresponding adjustments over the therapeutic decisions. Objective: characterization of microbiological spectrum of systemic infections, interpreting of isolate resistance to microbial agents Method and material: during January-December 2005, 3234 blood cultures have been processed using the BacT/Alert system. The positive samples have been identified using the MicroScan and MiniApi systems. Sensitivity testing has been conducted using semi-quantitative and/or quantitative techniques as per CLSI guidelines. The statistical interpretation of data has been done using the Whonet5.3 and Excel programs. Results: a total of 197 real positive blood cultures have been identified (6.09%) of which 2 were fungi and 195 bacterial from which Gram-pozitive cocci (67%) and Gram-negative bacilli (31,97%). Conclusions: re-emergence of Gram-positive cocci as a cause of blood infections with high incidence of S. aureus (20,40%) and equal incidence of coagulase-negative staphylococci with E. coli (18,87%). Increased resistance to antibiotics for MRSE (54,1% ), MRSA (50%), E. coli (18%) and K. pneumoniae (64%) ESBL producing.

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Resistance to beta-lactamines of several pathogenic germs

Carmen Avramescu, Maria Balasoiu, Adriana Turculeanu, Anca Ungureanu, Isabela Silosi, Simona Neamtu, Oana Ionete, Madalina Sibiseanu
Abstract: Premises The antibiogram is one of the most frequent determination from a bacteriology laboratory being required on multiple clinical, epidemiological and research considerations. Scientifically, antibiogram is made for the research of the resistance phenomenon through which the bacterias with etiological role in human infections are or become resistant to antibiotics. Objectives The object of the study is to estimate the resistance of the several pathogenic germs (Klebsiella, Escherichia coli, Proteus, Staphylococcus aureus) isolated from various pathological products, to several betalactamic antibiotics usually used in medical practice: Imipenem+Cilastatin, Ampicillin+Sulbactam, Ampicillin+Acid clavulanic, Cefotaxim, Ceftazidim, Ampicillin. Material and method In our study, there were used bacterian cultures isolated from pathological products from a lot of 37 adult patients, most of them with urogenital pathology and acute or chronic respiratory infections affections. The sensibility and resistance of the pathogenical germs reminded before using difusimetrical antibiogram. Results and conclusions E. coli became resistant to Imipenem+Cilastatin, the sensibility of Klebsiella and Proteus was not modified, while the sensibility of the Staphylococcus dropped, although the Staphylococcus remained receptive to this antibiotic. E. coli kept its sensibility towards Ampicillin+Acid clavulanic action unlike the other studied germs where a tendency to became resistant was observed. The Ampicillin+Sulbactam only E. coli and Proteus have an intermediate sensibility. The Staphylococcus is the one who responds best to Cefotaxim therapy, followed by Proteus. In the case of Klebsiella, one can, one can see the tendency to become resistant to this antibiotic, while in the case of the E. coli the definitive resistance to Cefotaxim is observed. None of the germs are sensible anymore to Ceftazidim. Towards Ampicillin it is observed the tendency to become resistant, only the Staphylococcus and Proteus have an intermediate sensibility.

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Inferior urinary tract infections

Maria Balasoiu, Adriana Turculeanu, Carmen Avramescu, A.T. Balasoiu
Abstract: Our study refers to 30 urinary prelevates from diabetic patients with benign and malign urological affections, whom have been diagnosticated with inferior urinary tract infections. The prelevates were isolated on solid Saboroud. Both identification of Candida species and resistance test were done using CANDIFAST ELITECH France SAS kit. 18 species from the total number of 30 were Candida albicans, 5 were Candida krusei, 4 were tropicalis and 3 were saccharomyces. Antifungical agents sensibility was different from one species to another, most species presented high sensibility to Flucitosyn, Econazol, Miconazol and reduced sensibility to Ketoconazol and Nystatin.

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Therapeutical Practice

Principles of optimal nutrition in children undergoing peritoneal dialysis

Alex R. Constantinescu
Abstract: The pediatric patient on peritoneal dialysis is faced with a significant risk for malnutrition and subsequent growth and developmental delay. By recognizing the patients needs, and the obstacles in meeting them, the medical team can tailor an individualized therapy, optimal for each patient. The particular requirements for growing children, as well as few major issues of optimal nutrition of the patient on peritoneal dialysis are discussed in this article. peritoneal dialysis, growth, development, nutrition

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Nutritional therapy in Crohns disease in children

Gabriela Lesanu
Abstract: Twenty-five percent of individuals diagnosed with Crohns disease (CD) have onset of disease in childhood. Growth failure was noticed in 15-40% of the children with inflammatory bowel disease, with a significant number of children having impaired linear growth. The suppression of linear growth that occurs in children with CD has been attributed chiefly to malnutrition; however, there is evidence that the inflammatory process may itself be major factor in leading to growth retardation. A possible mechanism of action of enteral nutrition (EN) in inducing disease remission in CD is the capacity of modification of gut microflora. Enteral formulas may also directly reduce inflammation, lowering the expression of cytokines like interleukin (IL)-6. It is recommended EN to be the first line of treatment for all children with Crohns disease, both for small and large intestinal disease. NE may be effective both by restoring nutrition when impaired or inducing a remission of disease activity. Supplementary enteral nutrition after primary therapy and after remission is induced may be associated with the prolongation of remission and promotion of linear growth.

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Calcium needs in childhood

Doina Anca Plesca
Abstract: Childhood is defined as a dynamic growth process with a variable rate depending on age. Estimations state that osseous mass grows 7 times from birth to puberty. The calcium needs for human body varies significantly throughout the rapid growth period (childhood, puberty), pregnancy and nursing. The adequate calcium intake leads to an optimum osseous mass diminishing the risks of fractures and osteoporosis in adults. Respecting therapeutic guidelines recommendation, reporting on calcium dietetic daily ratio is a must for covering the calcium needs of the human body. There is an abyss between the daily dietetic recommendation and the real intake of calcium.

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Rare form of cutanat collision tumor: malignant basomelanocytic tumor

Sabina Zurac, G. Petsakos, R. Andrei, Florica Staniceanu, Alexandra Bastian, Gianina Micu, Luciana Nichita, Virginia Chitu
Abstract: Childhood is defined as a dynamic growth process with a variable rate depending on age. Estimations state that osseous mass grows 7 times from birth to puberty. The calcium needs for human body varies significantly throughout the rapid growth period (childhood, puberty), pregnancy and nursing. The adequate calcium intake leads to an optimum osseous mass diminishing the risks of fractures and osteoporosis in adults. Respecting therapeutic guidelines recommendation, reporting on calcium dietetic daily ratio is a must for covering the calcium needs of the human body. There is an abyss between the daily dietetic recommendation and the real intake of calcium.

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Hypothermia, a neuroprotective therapeutic method between benefits and risks

A. Muresan, R. Macovei; D. Alexianu, M. Prazaru
Abstract: Therapeutic hypothermia may be of benefit in improving neurological outcomes in hypoxic cerebral injury after cardiac arrest. Its positive effects are enlarged to different kinds of pathologies including uncontrolled intracranial hypertension after traumatic brain injury, after ischemic acute stroke, myocardial infarction and even in case of acute liver failure. Hypothermia is part of surgery protocol for heart and great vessels surgery. Neuroprotective positive results are reported by several clinical studies but remains in debate questions like target temperature, cooling methods, duration of cooling, rewarming and hypothermia itself.

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Strontium clinical and paraclinical aspects

Gina Caragea, M. Ionica, R. Macovei
Abstract: Stable Strontium -meaning nonradioactive- is nontoxic, even when administered in large doses for prolonged periods. It also appears to be one of the most effective substances yet found for the prevention and treatment of osteoporosis and other bone-related conditions. Because of its chemical similarity to calcium, strontium can replace calcium to some extent in various biochemical processes in the body, including replacing a small proportion of the calcium in hydroxyapatite crystals of calcified tissues such as bones and teeth. Hemodialysis patients are at risk of developing trace element imbalances. Material and method: In order to detect strontium in whole blood and dialyzed fluid, the authors developed a routine technique using one AAS Varian system SpectraAA-880 with GTA-100, PSD and Neslab CFT-33 refrigerated recirculator, dominick hunter hydrogen generator and Ar gas 99.999% Linde Conclusion: Sr determination in the monitoring and diagnosis of Sr overload/deficiency and treatment follow-up might become important because Sr has a potential therapeutic value in the prevention and treatment of osteopenic disorder.

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Clinical and paraclinical corellations in acute poissoning with phenobarbital

Ruxandra Avram, Gina Caragea, M. Ionica, R. Macovei
Abstract: The acute intoxication with barbiturates, still widely used in medical practice, is a redoubtable matter, especially when long acting compounds are involved; because they have a long half time, slowly accumulate at the tissue level and lead to severe poisoning which require promptly intensive care measures. Case report: male patient 34 years old with a history of epilepsy and postencephalytic paralysis was admitted in the Toxicology Department 24 hours after the ingestion of a barbiturate overdose. The clinical state was very severe and required complex intensive care therapy. Daily measurements of plasmatic Phenobarbital levels settled a direct correlation between the positive outcome trend and decreasing barbiturates values. Conclusion: The active screening of the plasmatic phenobarbital levels is very useful especially when it comes to decide if more aggressive therapeutic measures are necessary.

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Primary Esophageal TB An Unusual Cause Of Dysphagia

Alina Sanda
Abstract: Primary esophageal TB in the absence of extra esophageal disease is exceedingly rare. The combination of the AIDS epidemic with the upsurge in reported cases of systemic TB has increased the incidence of esophageal infection in developed countries. In our patient however no cause for immunosuppression was found which makes this a unique case. TB may present as a primary esophageal disease without pulmonary involvement. Esophageal TB in absence of HIV infection is exceedingly rare. Symptoms of both esophagitis and dysphagia can be seen. The symptoms of esophageal TB depend on the degree and type of involvement. Pulmonary complaints often predominate because of the common occurrence of fistula to trachea, bronchus, or pleural space. Sometimes, formation of long strictures or traction diverticula causes dysphagia. Upper gastrointestinal hemorrhage has also been reported. The condition usually responds to standard antitubercular therapy.

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HIV associated to extrapulmonary tuberculosis

Victoria Birlutiu
Abstract: We present the case of C.I., a 16 years old female patient, diagnosed with human immunodeficiency virus (HIV) infection since September 2006 (the suspicion beginning from a genital condilomatosis). Our patient had contact with a multidrug-resistant TBC patient (her stepmother), who abandoned the tuberculostatic therapy several times. Our patient hospitalized in December 2006, accused fever, vomiting, diffuse abdominal pain, abdominal muscle contraction. During surgical procedure, mesenteric lymph nodes fistulized into colon and duodenum were discovered, against which right hemicolectomy, duodenorrhaphy, drainage, mesenteric lymphadenectomy were used. Before hospitalize, urocultures already confirmed urinary tuberculosis, with BK rifampin- and isoniazid-resistant, but sensible to pyrazinamide, ethambutol, cycloserine, amikacin. The patient was growing worse and 4 weeks from operation she died.

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Case Report

Arhive Category