Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.     

Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.     

The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.     

Serum iron levels in schizophrenic patients with or without akathisia.

The pathophysiology of akathisia still remains controversial. Iron deficiency was proposed to be an important factor in the development of akathisia. In the present study, it was aimed to compare levels of serum iron and linked variables in chronic akathisic (n=30), and non-akathisic patients (n=30) with schizophrenia and healthy controls (n=30) because of the controversy in the association of iron and akathisia. The Barnes Akathisia Scale for akathisia and Simpson-Angus Rating Scale for extrapyramidal side effects were used. Serum iron and linked variables and hematological profile of the patients and control subjects were determined. Serum iron levels were significantly lower both in akathisic and non-akathisic groups compared to the control group (P<0.001). Moreover, akathisic patients had significantly lower iron levels than non-akathisic patients (P<0.05). Total iron binding capacity was significantly higher in patients with akathisia compared to the control group (P<0.01). Although non-akathisic patients had a mild increase in total iron binding capacity, it was not statistically significant compared to the control group (P>0.05). Ferritin levels were determined to be significantly lower in both groups compared to the control group (P<0.01). In addition, there was a significant difference in ferritin levels between the patients with and without akathisia (P<0.05). In conclusion, our results support the hypothesis that an association between akathisia and iron metabolism exists.     

Partially de-epithelialised and buried V-Y advancement flap for reconstruction of sacrococcygeal and ischial defects.

Defects in the sacrococcygeal and ischial soft tissues can be treated with gluteus maximus and posterior thigh V-Y advancement flaps. However, late complications include recurrence and dehiscence of the suture line. Increasing the amount of the soft tissues over the bony prominences and multilayered closure may have an advantage for long-term durability. We modified the V-Y advancement technique by de-epithelialising the medial parts of the flap and burying them under the opposing edge of the wound or the flap. Sixteen patients with various defects of the sacrococcygeal and ischial soft tissues were operated on using this technique. All the flaps healed well with no partial or complete loss of the flap. Three patients developed complications. The main advantage of our technique is the use of healthy tissues to obliterate the dead spaces under the edges of the wound or the opposing flap. In this way, not only the defect in the skin but the defect in the subcutaneous tissue, with its iceberg tip at the surface, is treated effectively. To have an additional layer of tissue between the bone and the superficial tissues provides an extra cushion of soft tissue and avoids putting the suture line directly over the bony prominences. We used this modification safely for both unilateral and bilateral flaps. It could also be used successfully in other parts of the body.     

Disability,depression and somatization in a low back pain population

Objective: The aim of this study was to determine the prevalence of low back pain (LBP) in a primary care setting population and examine its association with the symptoms of depression and somatization. Methods: This is a cross‐sectional study, utilising a survey carried out in primary health care clinics (PHCs) in Al‐Ain, United Arab Emirates (UAE). A multistage stratified sampling design was used and a representative sample of 1304 UAE nationals aged 18–65 years who attended PHC clinics for any reason were included and 1103 (84.5%) subjects agreed to participate and responded to the questionnaire during a period from June 2001 to January 2002. A specially designed questionnaire with three parts was used for the data collection: socio‐demographic information of the studied subjects, modified version of the Roland‐Morris scale for evaluating back‐related functional disability and SCL‐90 R for depression and somatization subscales was used to assess depressive and somatic symptoms. Results: Of the total number of subjects surveyed (1103), 586 (53.1%) were men and 517 (46.9%) women. The mean age was 34.9 ± 13.4 years for men and 33.5 ± 11.8 years for women. The prevalence of LBP in the studied subjects was 64.7% (95% CI, 60.7–68.5] with 46.7% among men and 53.3% among women. There were a significant differences between the subjects with LBP and without LBP with respect to gender (P < 0.001), body mass index (BMI) (P < 0.001), occupational status (P < 0.001) and living environment (P = 0.016). Functional disability was higher in patients with LBP. Young patients in aged 15–34 years, patients with preparatory/secondary educational level and students showed higher depressive symptoms. A similar pattern was found in patients with somatic symptoms. Factor analysis revealed a strong association between depression and somatization in LBP patients. Conclusions: Functional disability was higher in with LBP. Furthermore, symptoms of depression and somatization are prevalent among LBP patients.     

Does off-pump coronary artery bypass reduce the incidence of post-operative atrial fibrillation? A question revisited.

Atrial fibrillation (AF) is the most common post-operative complication in patients undergoing coronary artery bypass grafting, with an increased incidence associated with advancing age. This study aims to determine whether off-pump coronary artery bypass (OPCAB) reduces the incidence of AF in a generalized population (mean age <70 years). A meta-analysis was performed including all randomised and propensity score matched non-randomised studies published between 2001 and 2003 reporting a comparison between the two techniques in a generalised patient group (average age <70 years). The primary outcome of interest was post-operative AF. Sensitivity analysis was performed to evaluate consistency of the calculated treatment effect. Fourteen studies fulfilled our inclusion criteria, including a total of 16,505 subjects. The incidence of AF was 19% (1612/8265) in the off-pump group versus 24% (1976/8240) in the on-pump group. When considering only the 11 randomised studies (2207 subjects), we found a significant reduction in the incidence of post-operative AF in the off-pump group using a random-effect model (odds ratio (OR)=0.60, 95% confidence interval (CI)=0.45-0.82, and chi-square of heterogeneity=18.02, P=0.05). Sensitivity analysis highlighted one randomised study causing funnel plot asymmetry, exclusion of which resulted in a significant reduction in the incidence of post-operative AF in the off-pump group (OR=0.71, 95% CI=0.57-0.90), with a non-significant heterogeneity of 3.91 (P=0.92). When only studies of high quality were considered (898 patients), no significant difference was seen between on and off-pump groups (OR=0.78, 95% CI=0.57-1.07, and heterogeneity=0.53, P=0.91). This may be due to small number of patients in this group. Our results suggest that although OPCAB surgery may reduce the incidence of post-operative AF in a generalised population (age <70 years) this finding is not clearly supported by high quality randomised trials. Although previous evidence suggests that the incidence of post-operative AF is reduced in an elderly population (>70 years) with off-pump surgery, our results show that the evidence is less clear in a younger population group. The question of whether off-pump surgery in this patient group results in a lower rate of post-operative AF remains to be answered by further high quality randomised research.     

Reversed anterior interosseous flap.

Reversed flaps from the forearm have been firmly established for hand coverage. Each has its own advantages and disadvantages. The reversed anterior interosseous flap is one option with special advantages in hand reconstruction. From January 2002 to July 2003 we used this flap in five consecutive male patients aged between 36 and 59. The defects were located on the first web space (2), on the dorsal side of the thumb (1), on the first metacarpal bone (1), and on the volar side of the wrist (1). Flap size was between 6 x 3 cm and 11 x 7 cm. All flaps healed without any problem and no complication was observed during the postoperative period. The major advantage of this flap is the preservation of the main arteries of the upper limb. Other advantages are as follows: good texture and colour for hand reconstruction, satisfactory rotation arc, and availability of composite and fascial flaps. Besides its advantages, the major disadvantages are unsightly donor area scar and the need for meticulous technique. As a conclusion, we found this flap very useful in hand reconstruction for coverage of small and moderate sized soft tissue defects of the hand.     

A reverse-flow composite flap in the rat.

Reverse-flow flaps are currently particularly used for the reconstruction of defects of the distal part of the extremities. Despite their common usage there have been many reports of postoperative complications, especially resulting in partial or total flap necrosis. There is insufficient knowledge of flap haemodynamics, physiology and wound healing properties in reverse-flow flaps. Development of the proper experimental models is needed to investigate these issues. The purpose of this study was to describe a new reverse-flow flap model in the rat. A total of 20 adult Wistar rats weighing 200-250 g were used in this experiment. In five rats, the vascular anatomy of the auricle of the rat was determined by anatomic dissection and microangiography. In the experimental group (N=5), 1x1 cm reverse-flow composite flaps were harvested as a semi-island shape, based on the distal course of the medial branch of the anterior auricular artery. In the control group, consisting of five rats, the flap was designed and raised based on the proximal course of the medial auricular artery, again in a semi-island shape. In the remaining five animals, a square-shaped composite tissue of the whole layer of the auricle, 1x1 cm in size, was harvested dividing all the bases circumferentially. The composite tissue was replaced in situ. While the former was considered a conventional antegrade-flow flap subgroup, the latter was designated as a graft subgroup. All flaps were replaced in situ. The survival of the flap was evaluated on postoperative day 7 by direct observation and microangiography. The skin island of all the reverse-flow flaps and conventional antegrade-flow flaps survived completely giving a success rate of 100%, whereas all grafts in the control group underwent complete necrosis. Microangiographic studies revealed the vascularity of the reverse-flow and antegrade-flow flaps, identifying the course of the auricular arteries. In conclusion, with its evident advantages of easy to design and harvesting, reliable survival pattern and consistent vascular structure, our new flap model will provide a means for future studies on flap haemodynamics, physiology in reverse-flow flaps.