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.     

Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.

     

Alternative impression technique for a speech-aid prosthesis.

OBJECTIVE: Prosthetic treatment for speech disorders attributable to surgically acquired soft palate defects are introduced. CASE: A patient who underwent soft palate resection for cancer is presented. The resected portion of the soft palate was confined to the posterior segments. A prosthesis with a speech bulb was adapted to the patient. CONCLUSION: Excellent restoration of speech and improvement of velopharyngeal function was achieved following placement of the special prosthesis.     

Peripheral Vascular Complication from Coronary Angiography: a Case Report of Cholesterol Embolization

A 65-year-old man developed acute limb ischemia, severe abdominal wall and lower limb livedo reticularis following a coronary angiogram. The differential diagnoses of acute limb ischemia and multiple cholesterol emboli syndrome (MCES) are discussed. This work was performed at Long Island Jewish Medical Center, 270-05, 76^th Avenue, New Hyde Park, NY 11040.     

Reinforcement of the suture line with an ePTFE graft attached with histoacryl glue in duodenal trauma.

BACKGROUND: Most duodenal injuries are managed with primary repair, but the degree of duodenal-wall injury may threaten the integrity of the primary repair. Therefore, we evaluated whether the primary repair site could be reinforced with histoacryl glue (HAG) or HAG with an expanded polytetrafluoroethylene (ePTFE) mesh. METHODS: Grade 3 duodenal injury in the second portion of the rat duodenum was chosen as a standard trauma model. Thirty-three male rats were divided into sham (n = 3), 2-layer primary repair (n = 10), 1-layer primary repair plus HAG application (n = 10) and ePTFE attached with HAG over the 1-layer primary repair site (n = 10) groups. Ten-day survival, adhesion grades and histological assessment were taken as outcome measures. RESULTS: A significant survival advantage was identified in the group that had an ePTFE graft attached with HAG over a 1-layer repair when compared with the group that had a 2-layer primary repair. Adhesion grades were found to be particularly increased in the group that had an ePTFE graft attached with HAG over the primary repair site, moderately increased in the primary repair plus HAG application group and lower in the 2-layer primary repair group. ePTFE graft application was found to be beneficial to coverage of the HAG-dependent empty spaces in the serosal layer. CONCLUSIONS: A primary repair site after duodenal trauma or a difficult duodenal stump can be reinforced with the application of HAG or ePTFE graft implantation with HAG.     

Sentinel health events surveillance in diabetes. Deaths among persons under age 45 with diabetes

The pilot study for a sentinel health events surveillance system for deaths among persons under age 45 with diabetes was conducted in six states in 1984 and 1985. Two hundred and thirty-three events were identified. Information from death certificates, physicians, and families revealed that 22% died from acute complications of diabetes and 53% from chronic complications. Blood pressure measurement and urinalysis testing had been performed in the last year for almost all of the decedents, but other preventive practices were reported less frequently. Hypertension was present in 57% and of those, was not controlled in 73%. Forty-four percent were cigarette smokers at the time of death. Agreement between physicians and families was generally higher for clinical conditions than for care practices. This surveillance system appears to yield information about the health care of persons with diabetes not readily available from other sources, although modifications may be necessary before implementation.