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.     

Sympathetic skin responses from postauricular region in Meniere's disease.

OBJECTIVE: To investigate the sympathetic nervous system activity in Meniere's disease (MD) by recording sympathetic skin responses (SSRs) from the postauricular region (PA). METHODS: Twenty-one patients with definite unilateral MD diagnosis and 12 healthy volunteers were studied by evoking right and left PA-SSRs with electrical stimulation of the left median nerve at the wrist in attack and interval periods of MD. Mean latencies and maximum amplitudes were used in statistical analyses. RESULTS: In unilateral definite MD patients, the mean latencies were longer and the maximum amplitudes were smaller on the involved ear side than those on the normal ear side (p<0.01 for both amplitude and latency) and than those from the controls (p<0.01 and p<0.05). In three patients, there was no detectable PA-SSR on the involved ear side while there were SSRs on the healthy side. In four patients, the responses were absent bilaterally during the attack period. CONCLUSIONS: There is a marked asymmetric sympathetic hypofunction in the area of the PA region of the involved ear in MD patients. SIGNIFICANCE: The PA region is a new site for recording sympathetic skin responses. PA-SSR is a useful tool to investigate sympathetic nervous system function in MD patients.     

Evaluation of leukocyte arylsulphatase a, serum interleukin-6 and urinary heparan sulphate following tamoxifen therapy in breast cancer.

Leukocyte arylsulphatase A (AS-A) was shown to be significantly high in newly-diagnosed breast cancer patients. Previous reports imply a connection between serum interleukin-6 (IL-6) and breast cancer, possibly through a modulation of enzymes involved in estrogen synthesis. Abnormal distribution of heparan sulphate proteoglycans (HSPGs) in malignant breast epithelial cells suggests that they play a key role in the regulation of cell growth. Estradiol is believed to be effective in modulating glycosaminoglycans (GAGs) and their depolymerizing enzymes. Therefore, in this study, attempts were made to evaluate the activity of leukocyte arylsulphatase A, serum interleukin-6, urinary GAGs and heparan sulphate (HS) in response to tamoxifen (TAM) therapy in mastectomised breast cancer patients. Thirty-four patients (aged 30-82 years) were administered TAM (20 mg twice daily). Blood and urine samples of each patient were collected three times (at the beginning, and in third and sixth month of TAM therapy), and biochemical parameters were measured. There was no difference between baseline leukocyte AS-A activity and that measured after three months. At the end of six months, enzyme activity was significantly higher than the former values (p=0.022), but within the reference intervals reported in the literature. Although this increase might imply a normalization, the duration of TAM therapy is not long enough to make a decision about either regression or aggravation of the disease. TAM did not have any effect on serum IL-6, urinary HS and GAG levels which may be due to insensitivity of these variables to TAM during the short period of therapy. Both urinary GAG and HS levels measured at sixth month exhibited a positive correlation with the baseline level of leukocyte AS-A (p=0.005 and 0.009, respectively), suggesting that positive responses to the drug might be seen in patients with low AS-A activity.     

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.     

A fluid level in an acute extradural haematoma

We report a fluid level in an acute extradural haematoma developing after placement of a ventriculoperitoneal shunt for hydrocephalus. This fluid level was thought to be due to a mixture of blood and cerebrospinal fluid.     

Detection of Pneumocystis carinii DNA in sputum and bronchoalveolar lavage samples by polymerase chain reaction.

A polymerase chain reaction (PCR)-based assay was developed for the detection of Pneumocystis carinii DNA in induced sputum and bronchoscopic alveolar lavage samples. The primer pair was selected from the published sequence of the thymidylate synthase gene of P. carinii derived from infected rats. The amplified DNA fragment of 403 bp was detected by agarose gel electrophoresis and by Southern and slot blot hybridization. No positive reaction was seen with DNA from different microorganisms typically found in the respiratory tract. P. carinii DNA was demonstrated in 30 of 42 sputum samples from immunosuppressed patients, whereas 21 of 42 sputum samples were positive by indirect immunofluorescence (IFL). Among the 42 patients, 14 were receiving prophylactic chemotherapy. In that group, PCR detected P. carinii in nine sputum samples, whereas IFL detected P. carinii in only four sputum samples. A positive PCR result was also seen in 5 of 43 IFL-negative bronchoscopic alveolar lavage samples from patients with respiratory symptoms. The PCR assay detected 10 copies of the target DNA, which corresponds to 10(-18) g of the specific P. carinii sequence. The results indicate that PCR amplification in combination with DNA hybridization is specific and is a more sensitive diagnostic method than IFL for the detection of P. carinii.