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.     

Gallbladder sludge and acute pancreatitis induced by acute hepatitis A.

In this case report, a young woman with gallbladder sludge and acute pancreatitis due to acute hepatitis A (HAV) is presented. She was admitted to our hospital with abnormal hepatic enzymes. Five days prior to her admission, an initial abdominal ultrasound was performed at another hospital and revealed no abnormality, while her serum aspartate aminotransferase (AST) level was at the upper limit of normal (ULN) x 8. A second ultrasound was performed at our hospital and revealed a gallbladder wall thickness (9.3 mm), gallbladder sludge in the gallbladder lumen, pancreatic edema, ascites, and hepatomegaly while AST was at the ULN x 50. Magnetic resonance imaging and magnetic resonance cholangiopancreatography revealed imaging features of an acute stage of pancreatitis and gallbladder wall thickness with coexisting sludge in the gallbladder lumen. HAV infection was diagnosed by the detection of immunoglobulin M against HAV in the serum. The patient underwent two repeated abdominal ultrasound examinations on the 5th (AST was at the ULN x 3) and the 20th days (AST was at the normal) after her discharge, and both revealed normal findings. In our case, we observed reversible changes in the hepatobiliary and pancreatic system which was related to the severity of hepatic necro-inflammation. HAV-associated pancreatitis may be due to the formation of biliary sludge during the acute phase of the viral illness, but this association needs further investigation.     

Clinical utility of dorsal sural nerve conduction studies in healthy and diabetic children.

OBJECTIVE: Monitoring of the dorsal sural sensory nerve action potential (SNAP) is a sensitive method for detection of peripheral neuropathies. We tried to determine the normal dorsal sural nerve conduction values of the childhood population and assessed the clinical utility of this method in diabetic children who have no clinical sign of peripheral neuropathy. METHODS: In the study, 36 healthy and 27 diabetic children were included. In all subjects peripheral motor and sensory nerve studies were performed on the upper and lower limbs including dorsal sural nerve conduction studies. RESULTS: The dorsal sural SNAP mean amplitude was 8.24+/-3.08 microV, mean latency was 2.47+/-0.48 ms, mean sensory conduction velocity was 41.63+/-5.43 m/s in healthy children. Dorsal sural SNAPs were absent bilaterally in one diabetic patient. In the other 26 diabetic patients, the mean dorsal sural nerve distal latency was longer (2.93+/-0.63 ms, P = 0.004), mean SCV was slower than in healthy subjects (36.68+/-7.66 m/s, P = 0.005). However, dorsal sural nerve amplitude was not different between the groups. A dorsal sural nerve latency of more than 2.9 ms had a sensitivity of 50% and a specificity of 75%. A dorsal sural nerve velocity of less than 36 m/s had a sensitivity of 54% and a specificity of 92%. CONCLUSIONS: We designated the reference values of the dorsal sural nerve in healthy children. In addition, our findings suggest that dorsal sural nerve conduction studies may have value to determine neuropathy in the early stages in children with diabetes. SIGNIFICANCE: The dorsal sural nerve conduction studies in diabetic children may have value to determine the neuropathy in its early stages.     

Adiponectin levels and atherosclerotic risk factors in pediatric chronic peritoneal dialysis patients.

BACKGROUND: Atherosclerotic vascular diseases are the major cause of mortality in patients with end-stage renal disease (ESRD) treated with chronic peritoneal dialysis (CPD), even in children. Adiponectin (ADPN) is a recently discovered adipocyte-derived plasma protein having anti-atherogenic properties. ADPN levels are elevated in ESRD but it has been reported that ESRD patients with low plasma ADPN levels have a high risk of cardiovascular death. OBJECTIVE: To clarify the atherosclerotic risk and especially the significance of ADPN levels in pediatric patients on CPD. DESIGN: Cross-sectional studyin the pediatric peritoneal dialysis unit of a university hospital. PATIENTS: 18 children, aged 12.6 +/- 5.6 years, being treated with CPD and 20 healthy age- and sex-matched control subjects were enrolled in this study. METHODS: Serum ADPN levels and other risk factors, including blood pressure, blood glucose, serum lipid/lipoprotein fractions, apolipoprotein B, C-reactive protein (CRP), lipoprotein(a), and homocysteine levels, were studied in CPD patients and compared to the controls. RESULTS: Serum ADPN levels were three times higher in the CPD group compared to the control subjects, as was previously reported. Apolipoprotein B and CRP levels were also high in the CPD group. No significant difference was found in other atherosclerotic parameters, including lipoprotein(a) and homocysteine levels. Interestingly, we found a negative correlation between log ADPN and creatinine levels among the CPD patients (r = -0.54, p < 0.05). There was no correlation between log ADPN and duration of CPD. Creatinine and low-density lipoprotein levels could account for 54% of the total variation in ADPN levels. CONCLUSION: Among pediatric CPD patients, serum levels of the anti-atherogenic protein, ADPN, were inversely associated with creatinine. ADPN level might be a novel marker to predict prognosis in pediatric CPD patients.     

Effects of topical application of methotrexate on nasal mucosa in rats: a preclinical assessment study.

OBJECTIVE: The aim of this study is to investigate dose-dependent effect of the topical application of methotrexate (MTX) in rats on the normal nasal mucosa, liver tissue, liver enzymes, and hemoglobin levels. STUDY DESIGN: Preclinical animal study. SETTING: Twenty male adult wistar albino rats were randomly divided into 4 groups (n=5). A single puff of MTX (2.5 microg) was applied to both nasal cavities 2 times a day. The animals were given MTX 1 day a week in group 1, 3 days a week in group 2, and 5 days a week in group 3. Control group animals were given 1 puff of physiologic saline to both nasal cavities 5 days a week and 2 times a day. After 28 days, liver biopsies, blood samples, and 5 nasal mucosal biopsies were taken. Histological examination was made with respect to certain parameters semiquantitatively (grade 0-3). The aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and hemoglobin counts were studied from blood samples. RESULTS: There are no statistically significant differences with respect to histopathological parameters between the control group and the groups 1-3 (P>0.05). Histopathological examination of liver tissue did not reveal any evident difference between the control and study groups. Mean AST and ALT as liver function tests and hemoglobin counts were within normal limits. Topical application of MTX at these doses has no toxic effect on the nasal mucosa, the liver tissue, AST and ALT levels, and hemoglobin level. CONCLUSIONS: These results have been encouraging to investigate use of the topical application of MTX in nasal manifestation of autoimmune disease or addition of the topical application of MTX to the steroid treatment in cases with massive nasal polyposis resistant to steroids and prone to recurrence.     

Incidence of the retroaortic left renal vein in patients with varicocele.

OBJECTIVE: The purpose of this study was to investigate the incidence of the retroaortic left renal vein (RLRV) in patients with varicocele. METHODS: The left renal vein was ultrasonographically investigated for the presence of the RLRV in 140 patients with varicocele and a control group of 137 age-matched patients. The main diagnostic criteria for varicocele were the presence of a varicose vein with a diameter of 3 mm or larger at rest and with a reflux lasting more than 2 seconds during the Valsalva maneuver. The RLRV was defined as a posterior course of the left renal vein to the aorta at the level of the origin of the superior mesenteric artery. RESULTS: The RLRV was observed in 13 (9.3%) of the 140 patients with varicocele and 3 (2.2%) of the control patients. The incidence of the RLRV was found to be significantly higher in patients with varicocele compared with the control patients (P = .018, Fisher exact test). In 13 patients with the RLRV, left varicocele and bilateral varicocele were detected in 10 and 3 cases, respectively. CONCLUSIONS: In this study, the incidence of the RLRV was found to be significantly higher in patients with varicocele compared with control patients. Thus, we suggest that the presence of the RLRV may be considered one of the etiologic factors in the development of varicocele.