Matrix metalloproteinase-2 polymorphism is associated with prognosis in prostate cancer

Objective: Prostate cancer (PCa) is the most frequent tumor in males in Brazil. Single nucleotide polymorphisms (SNP) have been demonstrated in the promoter region of matrix metalloproteinases (MMPs) genes and have been associated with development and progression of some cancers. In this study, our aim was to investigate a possible relation between polymorphism of the promoter region of the MMP2 gene and classical prognostic parameters in prostate cancer. Materials and methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction, using fluorescent probes (TaqMan). Results: In patients with tumors of a higher stage (pT3), a polymorphic allele in the MMP2 gene was more frequent (P = 0.026) than in patients with lower tumor stage. A polymorphic allele in the MMP2 gene was more frequent in Gleason >= 7 than in Gleason <= 6 (P = 0.042). Conclusions: We conclude that MMP2 polymorphism can be used together with pathological stage and Gleason score to identify patients with worse prognosis. Our results illustrate the potential use of MMP2 SNP as a molecular marker for prostate cancer. (C) 2010 Elsevier Inc. All rights reserved.

Endoscopic treatment of Roux-en-Y gastric bypass-related gastrocutaneous fistulas using a novel biomaterial

Background Roux-en-Y gastric bypass (RYGB) is amongst the commonest surgical intervention for weight loss in obese patients. Gastrocutaneous fistula, which usually occurs along the vertical staple line of the pouch, is amongst its most alarming complications. Medical management comprised of wound drainage, nutritional support, acid suppression, and antibiotics may be ineffective in as many as a third of patients with this complication. We present outcomes after endoscopic application of SurgiSIS (R), which is a novel biomaterial for the treatment of this complication. Design A case series of 25 patients. Methods Twenty-five patients who had failed conservative medical management of gastrocutaneous fistula after RYGB underwent endoscopic application of SurgiSIS (R)-an acellular fibrogenic matrix biomaterial to help fistula healing. Main outcome measures Fistula closure as assessed by upper gastrointestinal imaging and endoscopic examination. Results In patients who had failed medical management lasting 4-25 (median, 7) weeks, closure of the fistulous tract was successful after one application in six patients (30%), two applications in 11 patients (55%), and three applications in three patients (15%). There were no procedure-related complications. Conclusions Endoscopic application of SurgiSIS (R)-an acellular fibrogenic matrix-is safe and effective for the treatment of gastrocutaneous fistula after RYGB.

Genetic Polymorphisms of Matrix Metalloproteinases: Susceptibility and Prognostic Implications for Prostate Cancer

Purpose: Prostate cancer is the most common tumor in males in Brazil. Single nucleotide polymorphisms have been demonstrated to exist in the promoter regions of matrix metalloproteinase genes and they are associated with the development and progression of some cancers. We investigated the correlation between MMP1, 2, 7 and 9 polymorphisms with susceptibility to prostate cancer, and classic prognostic parameters of prostate cancer. Materials and Methods: Genomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by realtime polymerase chain reaction using TaqMan (R) fluorescent probes. Results: For the MMP1 gene the polymorphic allele was more common in the control group than in the prostate cancer group (p <0.001). For the MMP9 gene the incidence of the polymorphic homozygote genotype was higher in the prostate cancer group (p <0.001). For higher stage tumors (pT3) a polymorphic allele in the MMP2 gene was more common (p = 0.026). When considering Gleason score, the polymorphic homozygote genotype of MMP9 was more common in Gleason 6 or less tumors (p = 0.003), while a polymorphic allele in the MMP2 gene was more common in Gleason 7 or greater tumors (p = 0.042). Conclusions: MMP1 and MMP2 may protect against prostate cancer development and MMP9 may be related to higher risk. In contrast, MMP9 polymorphism was associated with a lower Gleason score and MMP2 polymorphism was associated with nonorgan confined disease.

Cavopulmonary anastomosis improves left ventricular assist device support in acute biventricular failure

Objective: Right ventricular failure during left ventricular assist device (WAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavopulmonary anastomosis on right ventricular loading and WAD performance in a model of severe biventricular failure. Methods: LVAD support was performed by means of centrifugal pump implantation in 14 anesthetized dogs (20-30 kg) with severe biventricular failure obtained by ventricular fibrillation induction. Animals were randomized to be submitted to classical cavopulmonary anastomosis (Glenn shunt) or to control group and were maintained under WAD support for 2 h. Left and right atrial, right ventricular and systemic pressures were monitored, white total pulmonary flow was simultaneously recorded by transonic flowmeters located on the superior vena cava and pulmonary trunk. Blood gas and venous lactate determinations were also obtained. Results: Ventricular fibrillation maintenance resulted in acute WAD performance impairment after 90 min in the control group, while animals with Glenn circuit maintained normal WAD pump flow (55 +/- 13 ml kg(-1) min(-1) vs 21 +/- 4 ml kg(-1) min(-1), p < 0.001) and better peripheral perfusion (blood lactate of 29 +/- 10 pg/ml vs 46 +/- 9 pg/ml, p < 0.001). Left and right atrial pressures did not change significantly, while right ventricular pressure was tower in animals with Glenn circuit (13 +/- 3 mmHg vs 22 +/- 8 mmHg, p = 0.005). Right ventricular unloading with Glenn shunt also resulted in superior total pulmonary flow (59 +/- 13 ml kg(-1) min(-1) vs 17 +/- 3 ml kg(-1) min(-1), p < 0.001). Conclusion: The concomitant use of cavopulmonary anastomosis during LVAD support in a model of severe biventricular failure limited right ventricular overloading and resulted in better hemodynamic performance. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Melanonychia: the importance of dermatoscopic examination and of nail matrix/bed observation

Melanonychia, from the Greek melaina, means black and is the result of an increased deposition of melanin on the nail plate, originating in the nail matrix. It may have different causes, including subungueal melanoma, making early etiologic diagnosis very important.

Automatic versus manual pressure support reduction in the weaning of post-operative patients: a randomised controlled trial

Introduction Reduction of automatic pressure support based on a target respiratory frequency or mandatory rate ventilation (MRV) is available in the Taema-Horus ventilator for the weaning process in the intensive care unit (ICU) setting. We hypothesised that MRV is as effective as manual weaning in post-operative ICU patients. Methods There were 106 patients selected in the postoperative period in a prospective, randomised, controlled protocol. When the patients arrived at the ICU after surgery, they were randomly assigned to either: traditional weaning, consisting of the manual reduction of pressure support every 30 minutes, keeping the respiratory rate/tidal volume (RR/TV) below 80 L until 5 to 7 cmH(2)O of pressure support ventilation (PSV); or automatic weaning, referring to MRV set with a respiratory frequency target of 15 breaths per minute (the ventilator automatically decreased the PSV level by 1 cmH(2)O every four respiratory cycles, if the patient`s RR was less than 15 per minute). The primary endpoint of the study was the duration of the weaning process. Secondary endpoints were levels of pressure support, RR, TV (mL), RR/TV, positive end expiratory pressure levels, FiO(2) and SpO(2) required during the weaning process, the need for reintubation and the need for non-invasive ventilation in the 48 hours after extubation. Results In the intention to treat analysis there were no statistically significant differences between the 53 patients selected for each group regarding gender (p = 0.541), age (p = 0.585) and type of surgery (p = 0.172). Nineteen patients presented complications during the trial (4 in the PSV manual group and 15 in the MRV automatic group, p < 0.05). Nine patients in the automatic group did not adapt to the MRV mode. The mean +/- sd (standard deviation) duration of the weaning process was 221 +/- 192 for the manual group, and 271 +/- 369 minutes for the automatic group (p = 0.375). PSV levels were significantly higher in MRV compared with that of the PSV manual reduction (p < 0.05). Reintubation was not required in either group. Non-invasive ventilation was necessary for two patients, in the manual group after cardiac surgery (p = 0.51). Conclusions The duration of the automatic reduction of pressure support was similar to the manual one in the postoperative period in the ICU, but presented more complications, especially no adaptation to the MRV algorithm. Trial Registration Trial registration number: ISRCTN37456640

Polymorphisms of the matrix metalloproteinases associated with prostate cancer

Prostate cancer (PCa) is the most common type of malignant tumor in Brazilian males. Single nucleotide polymorphisms (SNPs) have been demonstrated to be present in the promoter region of matrix metalloproteinase (MMP) genes and have been associated with the development and progression of some cancers. In this study, our aim was to investigate the association between the polymorphisms of MMP1, 2, 7, and 9 and susceptibility, and their correlation with the classic prognostic parameters of PCa. For genes MMP1, 2 and 9, the frequencies of the polymorphic homozygote genotypes were higher in the control group than in the PCa group (P<0.0001). We conclude that the MMP1, 2 and 9 polymorphisms are more common in the control group than in patients with PCa, and may have a protective effect in the development of this neoplasia.

ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and without monitoring central venous oxygen saturation

Introduction: The ACCM/PALS guidelines address early correction of paediatric septic shock using conventional measures. In the evolution of these recommendations, indirect measures of the balance between systemic oxygen delivery and demands using central venous or superior vena cava oxygen saturation ( ScvO(2) >= 70%) in a goal-directed approach have been added. However, while these additional goal-directed endpoints are based on evidence-based adult studies, the extrapolation to the paediatric patient remains unvalidated. Objective: The purpose of this study was to compare treatment according to ACCM/PALS guidelines, performed with and without ScvO(2) goal-directed therapy, on the morbidity and mortality rate of children with severe sepsis and septic shock. Design, participants and interventions: Children and adolescents with severe sepsis or fluid-refractory septic shock were randomly assigned to ACCM/PALS with or without ScvO(2) goal-directed resuscitation. Measurements: Twenty-eight-day mortality was the primary endpoint. Results: Of the 102 enrolled patients, 51 received ACCM/PALS with ScvO(2) goal-directed therapy and 51 received ACCM/PALS without ScvO(2) goal-directed therapy. ScvO(2) goal-directed therapy resulted in less mortality ( 28-day mortality 11.8% vs. 39.2%, p = 0.002), and fewer new organ dysfunctions ( p = 0.03). ScvO(2) goal-directed therapy resulted in more crystalloid ( 28 ( 20-40) vs. 5 ( 0-20) ml/kg, p < 0.0001), blood transfusion ( 45.1% vs. 15.7%, p = 0.002) and inotropic ( 29.4% vs. 7.8%, p = 0.01) support in the first 6 h. Conclusions: This study supports the current ACCM/PALS guidelines. Goal-directed therapy using the endpoint of a ScvO(2) = 70% has a significant and additive impact on the outcome of children and adolescents with septic shock.

A decision support system to facilitate management of patients with acute gastrointestinal bleeding

Objective: To develop a model to predict the bleeding source and identify the cohort amongst patients with acute gastrointestinal bleeding (GIB) who require urgent intervention, including endoscopy. Patients with acute GIB, an unpredictable event, are most commonly evaluated and managed by non-gastroenterologists. Rapid and consistently reliable risk stratification of patients with acute GIB for urgent endoscopy may potentially improve outcomes amongst such patients by targeting scarce health-care resources to those who need it the most. Design and methods: Using ICD-9 codes for acute GIB, 189 patients with acute GIB and all. available data variables required to develop and test models were identified from a hospital medical records database. Data on 122 patients was utilized for development of the model and on 67 patients utilized to perform comparative analysis of the models. Clinical data such as presenting signs and symptoms, demographic data, presence of co-morbidities, laboratory data and corresponding endoscopic diagnosis and outcomes were collected. Clinical data and endoscopic diagnosis collected for each patient was utilized to retrospectively ascertain optimal management for each patient. Clinical presentations and corresponding treatment was utilized as training examples. Eight mathematical models including artificial neural network (ANN), support vector machine (SVM), k-nearest neighbor, linear discriminant analysis (LDA), shrunken centroid (SC), random forest (RF), logistic regression, and boosting were trained and tested. The performance of these models was compared using standard statistical analysis and ROC curves. Results: Overall the random forest model best predicted the source, need for resuscitation, and disposition with accuracies of approximately 80% or higher (accuracy for endoscopy was greater than 75%). The area under ROC curve for RF was greater than 0.85, indicating excellent performance by the random forest model Conclusion: While most mathematical models are effective as a decision support system for evaluation and management of patients with acute GIB, in our testing, the RF model consistently demonstrated the best performance. Amongst patients presenting with acute GIB, mathematical models may facilitate the identification of the source of GIB, need for intervention and allow optimization of care and healthcare resource allocation; these however require further validation. (c) 2007 Elsevier B.V. All rights reserved.

Activation of the shoulder and arm muscles during axial load exercises on a stable base of support and on a medicine ball

The purpose of this study was to compare SEMG activities during axial load exercises on a stable base of support and on a medicine ball (relatively unstable). Twelve healthy male volunteers were tested (x = 23 +/- 7y). Surface EMG was recorded from the biceps brachii, anterior deltoid, clavicular portion of pectoralis major, upper trapezius and serratus anterior using surface differential electrodes. All SEMG data are reported as percentage of RMS mean values obtained in maximal voluntary contractions for each muscle studied. A 3-way within factor repeated measures analysis of variance was performed to compare RMS normalized values. The RMS normalized values of the deltoid were always greater during the exercises performed on a medicine ball in relation to those performed on a stable base of support. The trapezius showed greater mean electric activation amplitude values on the wall-press exercise on a medicine ball, and the pectoralis major on the push-up. The serratus and biceps did not show significant differences of electric activation amplitude in relation to both tested bases of support. Independent of the base of support, none of the studied muscles showed significant differences of electric activation amplitude during the bench-press exercise. The results contribute to the identification of the levels of muscular activation amplitude during exercises that are common in clinical practice of rehabilitation of the shoulder and the differences in terms of type of base of support used. (C) 2006 Elsevier Ltd. All rights reserved.

An association rule-based method to support medical image diagnosis with efficiency

In this paper, we propose a method based on association rule-mining to enhance the diagnosis of medical images (mammograms). It combines low-level features automatically extracted from images and high-level knowledge from specialists to search for patterns. Our method analyzes medical images and automatically generates suggestions of diagnoses employing mining of association rules. The suggestions of diagnosis are used to accelerate the image analysis performed by specialists as well as to provide them an alternative to work on. The proposed method uses two new algorithms, PreSAGe and HiCARe. The PreSAGe algorithm combines, in a single step, feature selection and discretization, and reduces the mining complexity. Experiments performed on PreSAGe show that this algorithm is highly suitable to perform feature selection and discretization in medical images. HiCARe is a new associative classifier. The HiCARe algorithm has an important property that makes it unique: it assigns multiple keywords per image to suggest a diagnosis with high values of accuracy. Our method was applied to real datasets, and the results show high sensitivity (up to 95%) and accuracy (up to 92%), allowing us to claim that the use of association rules is a powerful means to assist in the diagnosing task.

Morphologic evaluation and expression of matrix metalloproteinases-2 and 9 and nitric oxide during experimental periodontal disease in rat

The immunopathologic and inflammatory mechanisms involved in periodontal disease (PD) include the participation of host resident, inflammatory cells and chemical mediators. Metalloproteinases (MMPs) and nitric oxide (NO) play essential role in extracellular matrix turnover of periodontal tissue destruction. In this study, by means of RT-PCR through semi-quantitative densitometric scanning methods, the expression of MMPs -2 and -9 and inducible NO synthase (iNOS) was temporally and spatially investigated during the destructive mechanisms of experimentally induced PD in rats. Samples from different periods were microscopically analyzed and compared with the contralateral side (control). Our results showed significant expression of MMP-9 and iNOS in tissues affected by PD, as compared with controls, three days after PD induction, simultaneously with the beginning of alveolar bone loss. At 7 days post induction, only the MMP-9 mRNA presented a significantly higher expression, as compared with the respective controls. Thus, in the rat ligature-induced PD, MMP-9 and iNOS might importantly participate in the early stages of the disease, including inflammatory cell migration, tissue destruction and alveolar bone resorption. Also, we may suggest that the exuberant presence of PMNs may be related to the important expression of iNOS and MMP-9 found at 3 days post induction.

Increased activities of cardiac matrix metalloproteinases matrix metalloproteinase (MMP)-2 and MMP-9 are associated with mortality during the acute phase of experimental Trypanosoma cruzi infection

The strong inflammatory reaction that occurs in the heart during the acute phase of Trypanosoma cruzi infection is modulated by cytokines and chemokines produced by leukocytes and cardiomyocytes. Matrix metalloproteinases (MMPs) have recently emerged as modulators of cardiovascular inflammation. In the present study we investigated the role of MMP-2 and MMP-9 in T. cruzi-induced myocarditis, by use of immunohistochemical analysis, gelatin zymography, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction to analyze the cardiac tissues of T. cruzi-infected C57BL/6 mice. Increased transcripts levels, immunoreactivity, and enzymatic activity for MMP-2 and MMP-9 were observed by day 14 after infection. Mice treated with an MMP inhibitor showed significantly decreased heart inflammation, delayed peak in parasitemia, and improved survival rates, compared with the control group. Reduced levels of cardiac tumor necrosis factor-alpha, interferon-gamma, serum nitrite, and serum nitrate were also observed in the treated group. These results suggest an important role for MMPs in the induction of T. cruzi-induced acute myocarditis.

Matrix Metalloproteinase Inhibition Improves Cardiac Dysfunction and Remodeling in 2-Kidney, 1-Clip Hypertension

Background: Enhanced cardiac matrix metalloproteinase activity (MMPs) has been associated with ventricular remodeling and cardiac dysfunction. It is unknown whether MMPs contribute to systolic/diastolic dysfunction and compensatory remodeling in 2-kidney, 1-clip (2K1C) hypertensive rats. To test this hypothesis, we used 2K1C rats after 2 weeks of surgery treated or not with a nonspecific inhibitor of MMPs (doxycycline). Methods and Results: We found that blood pressure and +/-dP/dt increased in 2K1C rats compared with sham groups, and these parameters were attenuated by doxycycline treatment (P < .05). Doxycycline also reversed cardiac hypertrophy observed in 2K1C rats (P < .05). Hypertensive rats showed increased MMP-2 levels in zymograms and in the tissue by immunofluorescence (P < .05) compared with sham groups. Increased total gelatinolytic activity was observed in untreated 2K1C rats when compared with sham groups (P < .05). Doxycycline decreased total gelatinolytic activity in 2K1C rats to control levels (P < .05). Conclusion: An imbalance in gelatinolytic activity, with increased MMP-2 levels and activity underlies the development of morphological and functional alterations found in the compensatory hypertrophy observed in 2K1C hearts. Because function and structure were restored by doxycycline, the inhibition of MMPs or their modulation may provide beneficial effects for therapeutic intervention in cardiac hypertrophy. (J Cardiac Fail 2010;16:599-608)

Matrix metalloproteinase (MMP)-9 genotypes and haplotypes in preeclampsia and gestational hypertension

Background: Abnormal production of matrix metalloproteinases (MMPs), especially MMP-9, may play a role in hypertensive disorders of pregnancy. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 gene, which are known to change MMP-9 expression. We examined whether 2 MMP-9 polymorphisms (C(-) (1562) T and (CA)n) and haplotypes are associated with preeclampsia and/or gestational hypertension. Methods: We studied 476 pregnant women: 176 healthy pregnant (HP), 146 pregnant with gestational hypertension (GH), and 154 pregnant with preeclampsia (PE). Genomic DNA was extracted from whole blood and genotypes for C(- 1562) T and (CA)n polymorphisms were determined by PCR-RFLP. Haplotype frequencies were inferred using the PHASE ver. 2.1 program. Results: For the g.-90(CA)13-25 polymorphism, no significant differences were found in genotype and allele distributions when PE or GH groups were compared with HP group. However, the CT genotype and T allele for g.-1562C>T polymorphism were more commonly found in GH subjects compared with the HP group (both P<0.05). Conversely, we found no differences in genotypes or allele distributions for the g.-1562C>T polymorphism when the PE and the HP groups were compared. No significant differences were found in overall distributions of haplotype frequencies when the GH or the PE group was compared with the HP group. Conclusions: The C(- 1562) T polymorphism in MMP-9 gene is associated with gestational hypertension, but not with preeclampsia. These findings may help to explain the higher plasma MMP-9 levels previously reported in GH compared with HP. (C) 2010 Elsevier B.V. All rights reserved.