Endothelial Nitric Oxide Synthase Gene Intron 4 (VNTR) Polymorphism and Vascular Access Graft Thrombosis

Vascular access thrombosis is a leading cause of vascular access failure in hemodialysis patients. Thrombosis is a multifactorial condition and genetic makeup can affect thrombosis risk. We conducted a study to investigate for possible associations between ecNOS gene intron 4 variable-number tandem repeat (VNTR) polymorphism and thrombosis of polytetrafluoroethylene hemodialysis arteriovenous access grafts (AVG) in Turkish patients. Fifty-five patients with end-stage renal disease who had AVGs implanted between 2000 and 2002 and 167 healthy individuals representing our healthy population were enrolled in this prospective study. Each subject provided a venous blood sample from which DNA was isolated, and polymerase chain reaction analysis was done to identify genotypes (aa, bb, ab) for ecNOS gene intron 4 VNTR polymorphism. All grafts were placed in brachioaxillary position. The subjects were divided into two groups based on duration of graft patency. The thrombosis group (Group I) comprised 26 patients who developed AVG thrombosis in the first 12 months after placement. The no-thrombosis group (Group II) comprised 29 patients whose grafts remained patient for at least 12 months. The frequency of the aa genotype in Group I was significantly higher than that in Group II (p =. 005). At 6, 12, and 24 months, the primary patency rates for the AVGs in patients with the aa genotype were significantly lower than the corresponding rates for the bb and ab genotype groupings (p =. 01, p =. 01 and p =. 04 for the three respective time points; Kaplan–Meier). ecNOS gene intron 4 VNTR polymorphism is linked with the pathogenesis of vascular access thrombosis in Turkish patients undergoing hemodialysis.     

Setting Up a Successful Vagus Nerve Stimulation Service for Patients With Difficult-to-Treat Depression

BackgroundA substantial number of patients with major depressive disorder (MDD) do not sufficiently remit after the first lines of antidepressant treatments, making them vulnerable to poor clinical outcomes. Patients who have not had adequate resolution of their depressive symptoms after four antidepressant treatments and/or have been experiencing their current episode of MDD for two years or more (with insufficient responses to adequate antidepressant treatments) should be evaluated for antidepressant vagus nerve stimulation (VNS Therapy). Adjunctive VNS Therapy is a promising long-term treatment option for patients with difficult-to-treat depression (DTD), offering significantly improved remission rates in comparison with usual treatments. However, VNS Therapy requires specialized treatment centers to support patients.Materials and MethodsIn this narrative review, we aim to outline the necessary steps for setting up an antidepressant VNS Therapy service in an efficient manner.ResultsEstablishing a VNS Therapy service requires several high-level considerations: initiation of a collaborative multidisciplinary team of health care professionals; developing a surgical pathway for implantation; consideration of reimbursement and health care coverage; setting up a specialist clinic to identify optimal candidates for VNS Therapy; educating patients and their families about VNS Therapy; and training health care providers on patient-specific VNS Therapy treatment and long-term treatment management.ConclusionsAntidepressant VNS Therapy is a promising treatment option for the long-term treatment of patients with DTD. We have successfully initiated four VNS Therapy service centers for DTD in the United States, Austria, and Germany. Based on our experiences and lessons learned, herein, we have provided advice to psychiatric centers planning to set up a VNS Therapy service for their patients with DTD.     

Role of the Neutrophil-Lymphocyte Ratio in the Differential Diagnosis of Exudative Pleural Effusion

OBJECTIVES:Pleural effusion is a common diagnostic and clinical problem. The differential diagnosis of pleural effusion may be difficult and may require several procedures, including invasive ones. Certain studies have investigated biochemical parameters to facilitate the diagnosis of exudative pleural effusion; however, it remains a challenging problem in clinical practice. We aimed to investigate the potential role of the neutrophil-lymphocyte ratio, which can be easily obtained by determining the cell count of the pleural fluid, in the differential diagnosis of exudative pleural effusion.METHODS:Records from patients who underwent thoracentesis and pleural fluid analysis between May 1, 2013, and March 1, 2015, were obtained from the electronic database of our hospital. The patients who met the inclusion criteria were divided into five groups according to their diagnosis: malignant pleural effusion, para-malignant pleural effusion, para-pneumonic effusion, tuberculosis-related effusion or other. The neutrophil-lymphocyte ratio value was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The patient groups were compared according to the given parameter.RESULTS:A total of 465 patients who met the inclusion criteria among 1616 patients with exudative pleural effusion were included in the study. The mean neutrophil-lymphocyte ratio value was significantly lower in tuberculosis-related pleural effusion compared to malignant, para-pneumonic and para-malignant effusions (p=0.001, p=0.001, p=0.012, respectively). The areas under the curve for tuberculosis pleurisy compared to malignant, para-pneumonic and para-malignant effusions were 0.38, 0.36, and 0.37, respectively. Lower cut-off values had higher sensitivity but lower specificity for tuberculosis pleurisy, while higher cut-off values had higher specificity but lower sensitivity for this condition.CONCLUSION:The pleural fluid neutrophil-lymphocyte ratio, which is an inexpensive, reproducible, and easily calculated hematological parameter, may facilitate the differential diagnosis of pleural effusion.     

Expression profile of Toll-like receptor 4 in rat testis and epididymis throughout postnatal development

Toll-like receptors (TLRs) belonging to pattern recognition receptors are involved in maintaining testicular and epididymal immune homeostasis. The purpose of the current study was to investigate TLR4 expression in rat testis and epididymis throughout postnatal development. Weak staining was detected in peritubular myoid cells and immature Sertoli cells while no staining was observed in gonocytes during prepubertal period. However, TLR4 expression began to appear in spermatocytes in pubertal period and gradually increased in spermatids. An intense staining was observed in steps 5–19 spermatids in post pubertal and mature periods. Similarly, TLR4 expression in the testes steadily increased from pubertal period to mature period. Puberty also caused a significant increase in TLR4 expression in epididymis. TLR4 expression in cauda epididymis was lower as compared to those of other epididymal segments. The majority of epididymal epithelial cells exhibited apical TLR4 expression, whereas basal cells showed intense intracytoplasmic immunoreaction. We detected an intense staining in epididymal smooth muscle cells. The expression levels of TLR4 showed dynamic changes in both spermatogenic cells, and entire testicular and epididymal tissues during postnatal development. These results suggest that TLR4 expression contributes not only to inflammation but also to the development of spermatogenic cells.     

The relationship between the severity of erectile dysfunction and aortic stiffness

Aortic stiffness increases in patients with erectile dysfunction (ED) but it is not known whether aortic stiffness affects the degree of ED. In the present study, we aimed to determine whether there is any relationship between aortic stiffness and the severity of ED. Patients with ED were divided into 3 groups according to the International Index of Erectile Function (IIEF) scores. Mild ED was named as group 1, moderate ED as group 2 and severe ED as group 3. The values of fasting blood glucose (FBG), serum lipid values, total testosterone (T. tes), and free testosterone (F tes) were recorded. Aortic stiffness was determined by pulse wave velocity (PWV) and augmentation index (AIX) measurements. The mean or median values of the laboratory parameters among the groups were similar (p > .05). No statistical difference was found between the groups in terms of AIX value (p = .386). Mean PWV values were calculated as 7.26, 8.30 and 8.78 in group 1, group 2 and group 3 respectively. PWV values were significantly different between groups (p < .0001). PWV values were found to be increased with increasing severity of erectile dysfunction.     

Identification of intervertebral disc regeneration with magnetic resonance imaging after a long-term follow-up in patients treated with percutaneous diode laser nucleoplasty: a retrospective clinical and radiological analysis of 14 patients

Purpose

The aim of this study was to demonstrate regeneration of intervertebral discs undergoing laser therapy with sagittal relaxation time (T2) mapping after a long-term follow-up.

Materials and methods

Fourteen patients (9 men, 5 women; age range 20–57 years; mean age 36.5 years) treated with percutaneous 908-nm wave-length diode laser nucleoplasty for lumbar disc prolapsus at our clinic between January 2006 and June 2009 were studied. For the application of laser nucleoplasty in the past, patients who did not have central canal stenosis and/or lateral stenosis, sequestered disc fragment, operation scars and bleeding disorders were selected. The intervertebral disc levels undergoing laser therapy were L3–L4 (n = 2) or L4–L5 (n = 12). Patients were called for follow-up visits after a maximum 6-years (n = 2) or a minimum 3 years (n = 3) with a mean of 4.4 years. The patients’ clinical status for leg pain was evaluated according to the visual analog scale (VAS) and subsequently, a lumbar magnetic resonance imaging was performed. Sagittal T2 mapping was performed for the intervertebral discs undergoing laser nucleoplasty. We analyzed the relationship between T2 in the regions of interest (ROIs), which is known to correlate with changes in the composition of intervertebral discs, and the degree of degeneration determined using the Pfirrmann grading system and VAS of patients.

Results

On the basis of the evaluation of the results of intervertebral discs in all patients, there was a significant increase in T2 in the anterior NP (ROI 2, +10.3 ms; p < 0.05). A significant increase was noted in T2 in the middle NP (ROI 3, +24.6 ms; p < 0.001). The most significant increase was recorded for the posterior NP (ROI 4, +28.6 ms; p < 0.001). No significant decrease was found in T2 in the anterior and posterior AF (ROI 1, ?1.5 ms; p = 0.925; ROI 5, ?0.1 ms; p = 0.683). According to the Pfirrmann grading system, disc degeneration grades before laser therapy were recorded as grade III (n = 6) and grade IV (n = 8) whereas disc degeneration grades after laser therapy were found to be grade I (n = 6) and II (n = 8). A significant decrease was noted in Pfirrmann grades of disc degeneration after laser therapy (p < 0.0005).

Conclusions

In this study, there was a prolongation of T2 indicating regeneration in the nucleus pulposus after laser therapy and these results were found to be consistent with VAS measurements after a long-term follow-up. This study, which demonstrates the quantitative efficacy of laser therapy, indicates that MRG can be more effectively used in the future.     

Importance of acylcarnitine profile analysis for disorders of lipid metabolism in adolescent patients with recurrent rhabdomyolysis: Report of two cases

Metabolic myopathies due to disorders of lipid metabolism are a heterogeneous group of diseases. Newborns may present with hypotonia and convulsions, while progressive proximal muscle weakness or recurrent episodes of muscle weakness accompanied by rhabdomyolysis/myoglobinuria may be seen in older ages. There is little knowledge on detection of disorders of lipid metabolism by acylcarnitine profile (ACP) analysis by tandem mass spectrometry outside the neonatal period particularly in cases with recurrent rhabdomyolysis first presenting in adolescence and adulthood. Two adolescent female cases presented with episodes of rhabdomyolysis and muscle weakness. A 13-year-old patient had five episodes of rhabdomyolysis triggered by infections. Tandem mass spectrometry was normal. A 16-year-old female patient was hospitalized eight times due to recurrent rhabdomyolysis. Increased levels of C14:2, C14:1, and C14 were determined in tandem mass spectrometry. Final diagnoses were carnitine palmitoyltransferase II (CPT II) deficiency and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Increased serum levels of long-chain acylcarnitine can guide to the diagnosis of lipid metabolism disorders. Serum ACP should be performed before enzyme assay and genetic studies.