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.     

Effect of Acticoat® and Cutinova Hydro® on wound healing

In this study, the effects of the wound‐covering materials, Acticoat^® and Cutinova Hydro^®, on wound healing have been studied in rabbit models with open and tissue‐lost wounds with full‐thickness flank excisions. Rabbits were used as subjects with three groups of four rabbits each, and trial periods of 7, 14 and 21{\uns}days. Four circular wounds, of 1.5 cm diameter were made two on the right (one of them control) and two on the left (one of them control) of the dorsal sides of the abdomen. Acticoat^® and Cutinova Hydro^® were applied on the wounds with suture for a period of 21 days and one each placed on the right and left sides as control with gauze. Biopsy specimens were taken from the animals at the end of the research period to check the length of the epithelium, epithelial thickness, size of wounds, wound granulation tissue formation and histopathological evaluation for clarity. The Acticoat^® group showed better healing and scar formation compared to the Cutinova Hydro^® group by macroscopic examination. Epithelial wound length and clarity in terms of statistical difference occurred on day 21 (P <0.05); while the length of the wound epithelium decreased patency, epithelial thickness on days~7, 14 and 21, showed no statistical differences (P >0.05). As a result, the Acticoat^® wound dressing was determined as a more reliable for the early wound healing. This study has shown the short‐term clinical benefits of hydroactive, polyurethane dressings in the management of acute wounds. However, longer periods of wound healing procedure should be planned for reliable and safe results of wound dressing. It has also been concluded that microbiological analyses should be included for more robust and reliable comparisons.     

The effects of fetal allogeneic umbilical cord tissue transplant following experimental spinal cord injury on urinary bladder morphology

Background and purposeIn continuation of our previous experimental study on spinal cord injury (SCI) using fetal stem cells, we investigated here the effects of fetal allogeneic umbilical cord tissue transplant on the urinary bladder morphology in a rat SCI model.Material and methodsFive pregnant albino Wistar rats at 12 days of gestation were used to obtain the umbilical cord cell graft. In Group 1 (n = 5), Th8-Th9 laminectomy was performed. Group 2 (n = 5) received spinal cord injury. In Group 3 (n = 5), the cultured fetal umbilical cord cells coated with alginate gel were placed into the lesion cavity. In Group 4 (n = 5), only alginate sponges without umbilical cord cells were placed into the injury cavity. The bladders of animals were analyzed pathologically at 21 days after surgery.ResultsThe thickness of the epithelium and the lamina propria did not differ among studied groups (p > 0.05). The lamina muscularis thickness was significantly higher in Group 2 and Group 4 than the others (p < 0.05). The bladder weight was similar among Groups 1, 2, and 3 (p > 0.05). Fibrosis was significantly increased in Group 2 (p < 0.05); it was greater in Group 2 than in Group 3 (p < 0.05) but did not differ between Groups 1 and 3 (p > 0.05).ConclusionsThis study suggests that allogeneic umbilical cord tissue transplantation after SCI may prevent bladder wall hypertrophy and fibrosis in the rat SCI model.     

Decreased Activity and Genetic Polymorphisms of CYP2C19 in Behçet's Disease

Behçet's disease (BD) is a systemic autoimmune disorder. Cytochrome P450 enzymes (CYPs) are responsible for various drug metabolism reactions as well as those of endogenous substances which may be associated with autoimmune disease susceptibility. Recently, we reported that in patients with BD, CYP2C9 seems to be down‐regulated due to inflammation. In the same Turkish patients with BD, we investigated whether also CYP2C19 activity is decreased. Lansoprazole (30 mg) was given as a probe drug to evaluate CYP2C19 activity in 59 patients with BD and 27 healthy control volunteers. An HPLC method was used to determine plasma lansoprazole and its metabolite, 5‐hydroxy lansoprazole, concentrations. The genotyping for CYP2C19 *2, *3 and *17 polymorphisms was made using PCR‐RFLP. The median lansoprazole/5‐hydroxy lansoprazole metabolic ratio (MR) in patients with BD was 2.6‐fold higher as compared to the healthy control group (p = 0.001, 22.6 (1.3–26) and 8.8 (0.5–140) as median and range, respectively). The CYP2C19*17*17 genotype frequency was found to be significantly less in the BD group as compared to the healthy controls (1.7% versus 14.8% in controls, p = 0.01). Additionally, colchicine treatment did not affect the CYP2C19 enzyme activity in six patients (p = 0.43). In conclusion, the patients with BD had lower CYP2C19 enzyme activity and lower frequency of the CYP2C19*17 allele as compared to those of the healthy controls. Further studies are warranted on the mechanisms underlying this relation. This study should also be applied to other autoimmune diseases similarly characterized by local or systemic inflammation.     

A decision analysis to identify the ideal treatment for adult spinal deformity: is surgery better than non-surgical treatment in improving health-related quality of life and decreasing the disease burden?

Background

Adult spinal deformity (ASD) is a major public health problem. There are pros and cons of the available treatment alternatives (surgical or non-surgical) and it had been difficult to identify the best treatment modality.

Aim

To construct a statistical DA model to identify the optimum overall treatment in ASD.

Methods

From an international multicentre database of ASD patients (968 pts), 535 who had completed 1 year follow-up (371 non-surgical—NS, 164 surgical—S), constitute the population of this study. DA was structured in two main steps of: (1) baseline analysis (assessing the probabilities of outcomes, assessing the values of preference—utilities-, combining information on probability and utility and assigning the quality adjusted life expectancy (QALE) for each treatment) and (2) sensitivity analysis.

Results

Four hundred and thirty-two patients (309 NS, 123 S) had baseline and 1 year follow-up ODI measurements. Overall, 104 (24.1 %) were found to be improved (a decrease in ODI > 8 points), 225 (52.1 %) unchanged (?8 > ODI > 8) and 65 deteriorated. Surgery presented with a higher chance of improvement (54.2 %) versus NS (9.7 %). The overall QALE ranged from 56 to 69 (of 100 years) and demonstrated better final QALE in the NS group (60 vs. 65, P = 0.0038), this group having started with higher QALE as well (56 vs. 65 years, P < 0.0001). There were improvements in overall QALE in both groups but this was significant only in the surgical group (S from 56 to 60 years, P < 0.0001; NS from 65 to 65 years, P = 0.27). In addition, in the subgroup of patients with significant baseline disability (ODI > 25) surgery appeared to yield marginally better final QALE (58 vs. 56 years, P = 0.1) despite very a similar baseline (54 vs. 54 years, P = 0.93).

Discussion and conclusions

This study demonstrated that a single best treatment modality for ASD may not exist. Conservative treatment appears to yield higher (up to 6 %) QALE compared to surgery, most probably secondary to a higher baseline QALE. On the other hand, surgery provides a significantly higher increase in QALE. Especially in patients with significant disability at baseline, the final QALE tended higher in the S group (although not significant). Finally, chances of a relevant improvement at first year turned out to be significantly lower with NS treatment.