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.     

Aortic prosthetic ring annuloplasty: a useful adjunct to a standardized aortic valve-sparing procedure?

OBJECTIVE: Dilation of aortic annulus, sinuses of Valsalva, and sinotubular junction (STJ) diameters are the characteristic lesions of aortic root aneurysm. The remodeling technique reduces STJ diameter and creates three neosinuses of Valsalva. Alternatively, the reimplantation technique reduces both annulus and STJ diameters to the detriment of aortic root dynamics. Although the remodeling technique is recognized as the most physiological valve-sparing procedure, aortic annulus dilation may jeopardize its results. A standardized approach that combines an external subvalvular aortic prosthetic ring annuloplasty with the remodeling technique is suggested. METHODS: Eighty-three patients underwent an elective aortic root remodeling procedure, either isolated (group 1, n=34) or combined with an external subvalvular aortic prosthetic ring annuloplasty (group 2, n=49). Preoperative aortic regurgitation was 1.59+/-1.1 (group 1) and 1.97+/-1.3 (group 2) (NS). The aortic annulus was more dilated in group 2 than in group 1 (27+/-2.77 mm vs 26.4+/-2.3 mm, p<0.01). Residual aortic regurgitation > or =grade II was the conversion criteria for aortic valve replacement. RESULTS: Operative mortality was 3.6% (n=3). Intraoperative conversion for valve replacement was 32.7% in group 1 (n=11) versus 4.2% in group 2 (n=2) (p<0.001). In group 1, preoperative annulus diameter was larger for converted than for valve-spared patients (27.6+/-1.7 mm vs 25.2+/-1.5 mm, p<0.02). In group 2, implanted aortic ring significantly reduced annulus diameter (20.6+/-1.8 mm) without significant aortic valve gradient (8.3+/-3 mmHg). Follow-up was 17.2+/-13.4 months (group 1) and 10.41+/-7.95 months (group 2). Reoperation for recurrent aortic regurgitation was 13% in group 1 (n=3) versus 4.2% in group 2 (n=2). Echocardiographic follow-up found residual aortic regurgitation < or =grade I in 17 patients in group 1 (90%) versus 43 patients in group 2 (95.5%) and of grade II in two patients in group 1 (10%) and two patients in group 2 (4.5%). CONCLUSION: The addition of external aortic prosthetic ring annuloplasty improves the remodeling technique's operative reproducibility and short-term results. Therefore, its use as a systematical adjunct to the remodeling procedure is suggested. However, further long-term evaluation comparing this valve-sparing procedure to composite graft replacement should define the best surgical strategy for aortic root aneurysm.     

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.     

Season of birth and fluctuating asymmetry.

Fluctuating asymmetry (FA) refers to random, small deviations from perfect bilateral symmetry in morphological traits. These minor deviations from the ideal phenotype reflect environmental and genetic perturbations experienced during ontogeny. FA has been associated with negative health outcomes and many developmental disorders in humans. The prevalence of developmental disorders and adult health vary according to the month of birth, suggesting that seasonal stressors may leave enduring signs in the adult body, marked by high FA. The current study examined the relationship between FA and birth season. Data were collected for 205 males and females (average age = 20.39 years) on FA of 10 bilateral traits (second, third, fourth, and fifth digit length, palm height, wrist diameter, elbow width, ear height, foot breadth, and ankle circumference). Additional relationships were also investigated among FA, testosterone (T), and birth order. Results indicate that ear FA was lower for fall births compared to winter births in males. In females, palm FA was lower for fall births compared to those of the spring. FA of the digits was positively associated with T in males. Average FA, excluding the digits, decreased as the number of maternal siblings increased for both sexes. T concentrations in males were positively associated with the number of younger brothers. Our results generally confirm previous research on seasonal variation in adult longevity and neurological and psychiatric disorders, suggesting that winter and spring births are at risk for asymmetric developmental trajectory.     

Evaluation of the MS-2 automated antimicrobial susceptibility testing system: Report of a European collaborative study

The MS-2 is an instrument for rapid automated testing of antimicrobial susceptibility. Its performance was evaluated by comparison with disc diffusion and MIC tests in a collaborative study in four European laboratories. Tests on independently isolated organisms showed the MS-2 to be in essential agreement with conventional methods in 94.8% of tests. A further series of 170 welldefined pathogens for which a reference antibiogram was available were tested by MS-2 and the manual methods in all of the participating laboratories. MS-2 results were in full accord in 90 % of tests and in essential agreement in 94 %. MS-2 results compared at least as well with the reference values as did either of the manual methods. Initial problems of false susceptibility results with erythromycin and penicillin were resolved by (1) the addition of small amounts of erythromycin which acted as an inducer and (2) by the use of a low content penicillin disc. MS-2 was found to be reliable and needed no attention following loading of the test cuvette cartridges. A print-out of the results was available 2–5 h after inception of the test.     

Typhoid fever due to a Salmonella typhi strain of reduced susceptibility to fluoroquinolones

Objective: To report a case of typhoid fever contracted in Portugal in 1994 due to a Salmonella typhi isolate which had reduced susceptibility to fluoroquinolone (MIC 1 mg/L of ciprofloxacin) and high level resistance to nalidixic acid (MIC ≥56 mg/L).
Methods: Molecular studies of reduced susceptibility to fluoroquinolones comprised complementation tests with a wild-type allele and sequencing directly from PCR products of the gyrA gene.
Results: Complementation tests and DNA sequencing showed that a mutation occurred in the gyrA gene of this clinical isolate, resulting in a substitution of phenylalanine for serine at position 83 of GyrA.
Conclusions: Because quinolones may be regarded as a treatment of choice in typhoid fever, it seems important now to recommend cautious use of these drugs as first-line therapy and possibly use of nalidixic acid resistance as a marker for detection of 'first-step' resistance to fluoroquinolones in S. typhi.     

Comparative activity of teicoplanin and vancomycin against 400 penicillin susceptible and resistantStreptococcus pneumoniae

The MICs of teicoplanin and vancomycin were determined for 400 penicillin-susceptible and -resistant strains ofStreptococcus pneumoniae isolated during a multicenter study in 1992. Teicoplanin displayed a four-fold better activity than vancomycin, with modal MICs of these agents being 0.06 and 0.25 µg/ml, respectively. These data warrant further studies with teicoplanin in the treatment of pneumococcal infections.J. Akli, Centre Hospitalier Général, 41016 Blois Cédex; P. Allouch, Hôpital André Mignot, 78157 Le Chesnay Cédex; C. Bébéar, Centre Hospitalier Pellegrin-Tripode, 33076 Bordeaux Cédex; P. Blondel, Centre Hospitalier Général, 93205 Saint-Denis Cédex 1; A. Boisivon, Centre Hospitalier Général, 78104 Saint-Germain en Laye; J.C. Burdin, Hôpital Central, 54035 Nancy Cédex; H. Chardon, Centre Hospitalier Général, 13616 Aix en Provence Cédex; A. Coupry, Nouvel Hôpital de Fleyrat, 01012 Bourg-en-Bresse Cédex; J.C. Croix, Centre Hospitalier Général, 10003 Troyes Cédex; G. Dorche, Hôpital Bellevue, 42043 Saint-Etienne Cédex; P. Fiévet, Centre Hospitalier, 59507 Douai Cédex; F. Geffroy, Centre Hospitalier René Laënnec, 29107 Quimper Cédex; P. Geslin, Centre Hospitalier Intercommunal, 94010 Créteil; M.L. Grillot, Hôpital Général, 76083 Le Havre Cédex; B. Hautefort, Centre Hospitalier Général, 13697 Arles Cédex; M. Larrouy, Centre Hospitalier Intercommunal de la Côte Basque, 64109 Bayonne; H. Lefrand, Hôpital Henri Duffaut, 84902 Avignon Cédex 9; J.F. Lemeland, Hôtel-Dieu, 76000 Rouen; J.M. Libert, Centre Hospitalier Mane-Lannelongue, 92350 Le Plesssis-Robinson; A. Marmonier, Centre Hospitalier, 72037 Le Mans Cédex; M. Melon, Centre Hospitalier Général, 64011 Pau Cédex; M.H. Nicolas, Hôpital Ambroise Paré, 92104 Boulogne; J.C. Reveil, Hôpital Manchester, 08011 Charleville-Mézières Cédex; Y. Rio, Hôpital Notre Dame de Bon Secours, 57038 Metz Cédex; R. Sanchez, Hôpital Général, 24019 Périgueux Cédex; A. Sédaillan, Centre Hospitalier, 74011 Annecy Cédex, France.     

Sequence analysis of rpoB mutations in rifampin-resistant clinical Mycobacterium tuberculosis isolates from Turkey

Drug-resistant tuberculosis is a serious problem throughout the world. Resistance to Rifampicin (RIF) is mainly caused by the mutations in the rpoB gene coding the beta-subunit of RNA polymerase. In this study, we aimed to detect the distribution of rpoB gene mutations in 80 RIF-resistant clinical Mycobacterium tuberculosis (MTB) isolates from Turkey. The rpoB gene was amplified by PCR and mutations leading to RIF resistance were determined by automated sequence analysis. A total of 72 of the 80 isolates (90%) were found to carry mutations in the amplified region, whereas eight isolates (10%) carried no mutations. Overall, 24 different missense mutations affecting 14 codons, and two deletion mutants were identified. Nine new mutations, six in the hot-spot region and three outside this region, were found. The codon numbers of the most frequently encountered mutations were 531 (51.4%), 526 (18.1%), 516 (13.9%), and 513 (12.5%). As a result, 90% of the RIF-resistant MTB isolates from the Turkish patients were found to carry a mutation in the rpoB gene, Ser531Leu being the most frequent one. Although molecular methods identify mutations leading to RIF resistance very quickly, results of the antimycobacterial susceptibility tests must be taken into consideration for the patients carrying no mutations in this region.