CLINICALLY SIGNIFICANT PHARMACOKINETIC INTERACTIONS OF ANTIEPILEPTIC DRUGS

Antiepileptic drugs show clinically significant interactions among themselves as well as with other medications, because of a specific pharmacokinetic profile and relatively small therapeutic spectrum. The most significant clinical interactions of AE occur during their metabolism and distribution. In the combined antiepileptic therapy, it is very important to know the order of application of AE because of their influence on liver enzymes and the affinity to attach to plasma proteins. The AE with shorter half-time elimination have a greater potential for interaction which is why therapy monitoring is recommended. Populational pharmacokinetic analysis can provide significant information concerning interactions of AE with other medications. Vulnerable, pediatric population is under a special risk of developing interactions alongside patients with liver and kidney function damage

Focal neuroendocrine differentiation in prostatic gland carcinoma with basaloid pattern

Introduction. Prostatic gland basal cell proliferations exhibit morphological continuum ranging from basal cell hyperplasia to basal cell carcinoma. In the following report, we described clinical features, morphological spectrum, neuroendocrine differentiation and histogenesis of prostatic gland basal cell carcinoma in our patient. Case report. Hematoxylin- eosin (HE), Alcian blu-periodic acid schiff (ABPAS) at pH 2.5 stained sections and the avidin-biotinperoxidase complex (ABC), were performed on prostate gland paraffin-embedded tissue. Monoclonal antibodies directed against cytokeratin (34βE12) which selectively stains basal cells, prostate specific antigen (PSA), chromogranine A, neuron-specific enolase (NSE), synaptophysin and CD56, were used. Basal cell proliferations exhibited a morphological continuum ranging from basal cell hyperplasia to prostatic gland carcinoma. In these prostatic lesions, positive reactivity was demonstrated for 34βE12 and CD56. These findings indicate that the basaloid cells of basal cell hyperplasia, florid basal cell hyperplasia, atypical basal cell hyperplasia and basal cell carcinoma are derived from basal cells of the normal prostate gland suggesting a continuum in the progression of hyperplasia to benign and then malignant neoplasia. The presence of CD56 protein in the discovered lesions may be related to their neuroendocrine differentiation. Conclusion. The fact, that our patient was well six years after the radical prostatectomy supports the belief of some authors that basal cell carcinoma represents a low grade carcinoma with an excellent prognosis

Population Pharmacokinetics of Tacrolimus in Adult Kidney Transplant Patients: Impact of CYP3A5 Genotype on Starting Dose.

Objectives: The aims of this study were to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant recipients, to use this model to compare cytochrome P450 3A5 (CYP3A5) genotype-based initial dosing of tacrolimus with standard per-kilogram-based dosing, and to predict the best starting dose of tacrolimus based on patient genotype to achieve a trough concentration between 6 and 10 mu g/L by day 5 posttransplantation

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Focal neuroendocrine differentiation in prostatic gland carcinoma with basaloid pattern

Introduction. Prostatic gland basal cell proliferations exhibit morphological continuum ranging from basal cell hyperplasia to basal cell carcinoma. In the following report, we described clinical features, morphological spectrum, neuroendocrine differentiation and histogenesis of prostatic gland basal cell carcinoma in our patient. Case report. Hematoxylin- eosin (HE), Alcian blu-periodic acid schiff (ABPAS) at pH 2.5 stained sections and the avidin-biotinperoxidase complex (ABC), were performed on prostate gland paraffin-embedded tissue. Monoclonal antibodies directed against cytokeratin (34βE12) which selectively stains basal cells, prostate specific antigen (PSA), chromogranine A, neuron-specific enolase (NSE), synaptophysin and CD56, were used. Basal cell proliferations exhibited a morphological continuum ranging from basal cell hyperplasia to prostatic gland carcinoma. In these prostatic lesions, positive reactivity was demonstrated for 34βE12 and CD56. These findings indicate that the basaloid cells of basal cell hyperplasia, florid basal cell hyperplasia, atypical basal cell hyperplasia and basal cell carcinoma are derived from basal cells of the normal prostate gland suggesting a continuum in the progression of hyperplasia to benign and then malignant neoplasia. The presence of CD56 protein in the discovered lesions may be related to their neuroendocrine differentiation. Conclusion. The fact, that our patient was well six years after the radical prostatectomy supports the belief of some authors that basal cell carcinoma represents a low grade carcinoma with an excellent prognosis