Influence of ABCB1 polymorphisms and serum concentrations on venlafaxine response in patients with major depressive disorder

Background: The pharmacokinetics and the pharmacodynamics of antidepressants show large inter-individual variations which result in unpredictable clinical responses.

Aim: The aim of the study was to examine the effect of ABCB1 polymorphisms and the serum concentrations on the efficacy and tolerability of venlafaxine in patients with major depressive disorder (MDD).

Methods: Fifty-two outpatients who met the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) criteria for MDD were recruited for the study. The severity of depression was assessed using the 17-item Hamilton Rating Scale for Depression scale (HDRS₁₇) and tolerability was assessed based on a query regarding side-effects for 6 weeks. The ABCB1 C3435T/A and G2677T/A polymorphisms were genotyped by PCR/RFLP and steady-state serum venlafaxine concentrations were measured by high-performance liquid chromatography.

Results: Patients with the TT genotype for the C3435T and the TT/TA genotype for the G2677T/A polymorphism showed significantly higher frequencies in venlafaxine-induced akathisia. This relationship was not observed for efficacy. As regards serum venlafaxine concentrations, patient groups showed no significant differences in efficacy and tolerability.

Conclusion: The results suggest that individuals with the TT-TT/TA genotypes for the C3435T-G2677T/A polymorphisms of ABCB1 may be pre-disposed to a risk of akathisia.     

Molecular characterization of the influenza A(H1N1)pdm09 isolates collected in the 2015-2016 season and comparison of HA mutations detected in Turkey since 2009

Influenza A(H1N1)pdm09 pandemic virus causing the 2009 global outbreak moved into the post-pandemic period, but its variants continued to be the prevailing subtype in the 2015-2016 influenza season in Europe and Asia. To determine the molecular characteristics of influenza A(H1N1)pdm09 isolates circulating during the 2015-2016 season in Turkey, we identified mutations in the hemagglutinin (HA) genes and investigated the presence of H275Y alteration in the neuraminidase genes in the randomly selected isolates. The comparison of the HA nucleotide sequences revealed a very high homology (>99.5%) among the studied influenza A(H1N1)pdm09 isolates, while a relatively low homology (96.6%-97.2%), was observed between Turkish isolates and the A/California/07/2009 vaccine virus. Overall 14 common mutations were detected in HA sequences of all 2015-2016 influenza A(H1N1)pdm09 isolates with respect to the A/California/07/2009 virus, four of which located in three different antigenic sites. Eleven rare mutations in 12 HA sequences were also detected. Phylogenetic analysis revealed that all characterized influenza A(H1N1)pdm09 isolates formed a single genetic cluster, belonging to the genetic subclade 6B.1, defined by HA amino acid substitutions S84N, S162N, and I216T. Furthermore, all isolates showed an oseltamivir-sensitive genotype, suggesting that Tamiflu (Oseltamivir) could still be the drug of choice in Turkey.     

Does the use of recombinant TSH in preparation for I-131 scintigraphy scan affect hearing function?

Objective

The objective of this study was to examine the effect of hypothyroidism on hearing function in patients surgically treated for differentiated thyroid cancer and subsequently experienced hypothyroidism during preparation for follow up I-131 scintigraphy scan by either recombinant human thyroid stimulating hormone (rhTSH) treatment or thyroid hormone withdrawal (THW).

Does using the bispectral index (BIS) during craniotomy affect the quality of recovery?

One of the aims of neuroanesthesia is to provide early postoperative recovery and neurologic examination in patients undergoing supratentorial surgery. Our aim was to investigate the role of using the bispectral index (BIS) in recovery from anesthesia and altering drug administration in patients undergoing craniotomy. Fifty American Society of Anesthesiologists' (ASA) physical status I-II patients undergoing craniotomy were included in the study. The patients were randomly divided into two groups, and all patients received standard induction drugs, and 0.8%-1.5% sevoflurane was used for maintenance of anesthesia. In the BIS-guided group, the concentration of sevoflurane was titrated to maintain BIS at 40-60. In the control group, the anesthesiologist was blind to BIS, and the concentration of sevoflurane was changed according to the patients' hemodynamic changes. The hemodynamic data, BIS values, and sevoflurane concentrations were recorded every 15 minutes. In addition, the BIS value was recorded by the primary anesthetist in the BIS-guided group and by another independent anesthetist in the control group. At the end of the study, recovery criteria and Aldrete recovery scores were recorded every 15 minutes. Neurologic assessments were performed when the Aldrete score was 9-10. BIS values were higher, and sevoflurane concentrations (P < 0.05) and total doses of fentanyl (P < 0.01) were lower, in the BIS-guided group. Times to first spontaneous breathing, eye opening, and extubation (P = 0.035, P = 0.001, and P = 0.0001, respectively) were significantly shorter in the BIS-guided group. Time to an Aldrete score of 9-10 and adequate neurologic assessment were similar between the groups. In conclusion, BIS monitoring by supratentorial craniotomy under general anesthesia reduced the maintenance anesthetic concentration and narcotic drug usage and lowered the recovery times from general anesthesia.     

Intravesical analgesia for ambulatory urologic procedures: a histopathological study

Background and objective: Local anesthetics and morphine have been reported to be useful for painful diagnostic procedures in the bladder. Tramadol has the potential for use as an intravesical analgesic. However, intravesical use of tramadol has not been described widely. Methods: This study was approved by the Animal Ethical Committee of Akdeniz University and performed with standard guidelines for care and use of laboratory animals. In this study we tested the histopathological effects of intravesical tramadol versus saline in 20 adult rats. The control group received intravesically 1 ml saline. Tramadol 50 mg (1 ml) was administered intravesically in the other group. Two hours later, all animals were sacrificed and their bladders were excised. Tissue samples were evaluated macroscopically and microscopically. The data were analyzed with χ² and Fisher’s χ² tests. Results: In all the specimens in the control group epithelial edema was seen. This finding may be explained by insertion of intravesical catheter and tissue trauma. Haemorrhagic necrosis of epithelium was observed in four cases only in the tramadol group. This finding demonstrated severe epithelial destruction. However, there was no statistically significant difference when compared with the control group. Conclusion: The technique of topical tramadol anesthesia may be very simple, useful and safe for bladder biopsies and cautery in many cases. However, the number of cases examined in this preliminary study after bladder instillation of tramadol was small. For this reason, the results obtained in this study regarding the histopathological effects of tramadol on the bladder, should be further investigated.