European journal of medical research [journal]
- Molecular analysis of the CTSK gene in a cohort of 33 Brazilian families with pycnodysostosis from a cluster in a Brazilian Northeast region. [Journal Article]
- Eur J Med Res 2016; 21(1):33.
Pycnodysostosis is an autosomal recessive skeletal dysplasia, the prevalence of which is estimated to be low (1 per million). Nevertheless, in recent years we have found 27 affected individuals from 22 families in Ceará State, a region of the Brazilian Northeast, giving a local prevalence of 3 per million. This local prevalence associated with a high parental consanguinity, suggesting a possible founder effect, prompted us to perform a molecular investigation of these families to test this hypothesis.The CTSK gene was sequenced by the Sanger method in the patients and their parents. In addition to 18 families from Ceará, this study also included 15 families from other Brazilian regions. We also investigated the origin of each family from the birthplace of the parents and/or grandparents.We have studied 39 patients, including 33 probands and 6 sibs, from 33 families with pycnodysostosis and identified six mutations, five previously described (c.436G>C, c.580G>A, c.721C>T, c.830C>T and c.953G>A) and one novel frameshift (c.83dupT). This frameshift variant seems to have a single origin in Ceará State, since the haplotype study using the polymorphic markers D1S2344, D1S442, D1S498 and D1S2715 suggested a common origin. Most of the mutations were found in homozygosity in the patients from Ceará (83.3 %) while in other states the mutations were found in homozygosity in half of patients. We have also shown that most of the families currently living outside of Ceará have northeastern ancestors, suggesting a dispersion of these mutations from the Brazilian Northeast.The high frequency of pycnodysostosis in Ceará State is the consequence of the high inbreeding in that region. Several mutations, probably introduced a long time ago in Ceará, must have spread due to consanguineous marriages and internal population migration. However, the novel mutation seems to have a single origin in Ceará, suggestive of a founder effect.
- Waiting time for radiation therapy after breast-conserving surgery in early breast cancer: a retrospective analysis of local relapse and distant metastases in 615 patients. [Journal Article]
- Eur J Med Res 2016; 21(1):32.
Postoperative radiotherapy after breast-conserving surgery (BCS) is the standard in the management of breast cancer. The optimal timing for starting postoperative radiation therapy has not yet been well defined. In this study, we aimed to evaluate if the time interval between BCS and postoperative radiotherapy is related to the incidence of local and distant relapse in women with early node-negative breast cancer not receiving chemotherapy.We retrospectively analyzed clinical data concerning 615 women treated from 1984 to 2010, divided into three groups according to the timing of radiotherapy: ≤60, 61-120, and >120 days. To estimate the presence of imbalanced distribution of prognostic and treatment factors among the three groups, the χ2 test or the Fisher exact test were performed. Local relapse-free survival, distant metastasis-free survival (DMFS), and disease-free survival (DFS) were estimated with the Kaplan-Meier method, and multivariate Cox regression was used to test for the independent effect of timing of RT after adjusting for known confounding factors. The median follow-up time was 65.8 months.Differences in distribution of age, type of hormone therapy, and year of diagnosis were statistically significant. At 15-year follow-up, we failed to detect a significant correlation between time interval and the risk of local relapse (p = 0.09) both at the univariate and the multivariate analysis. The DMFS and the DFS univariate analysis showed a decreased outcome when radiotherapy was started early (p = 0.041 and p = 0.046), but this was not confirmed at the multivariate analysis (p = 0.406 and p = 0.102, respectively).Our results show that no correlation exists between the timing of postoperative radiotherapy and the risk of local relapse or distant metastasis development in a particular subgroup of women with node-negative early breast cancer.
- Stem cell procedures in arthroscopic surgery. [Journal Article, Review]
- Eur J Med Res 2016; 21(1):29.
The stem cell as the building block necessary for tissue reparation and homeostasis plays a major role in regenerative medicine. Their unique property of being pluripotent, able to control immune process and even secrete a whole army of anabolic mediators, draws interest. While new arthroscopic procedures and techniques involving stem cells have been established over the last decade with improved outcomes, failures and dissatisfaction still occur. Therefore, there is increasing interest in ways to improve the healing response. MSCs are particularly promising for this task given their regenerative potential. While methods of isolating those cells are no longer poses a challenge, the best way of application is not clear. Several experiments in the realm of basic science and animal models have recently been published, addressing this issue, yet the application in clinical practice has lagged. This review provides an overview addressing the current standing of MSCs in the field of arthroscopic surgery.
- Evaluation and clinical significance of cyclin-dependent kinase5 expression in cervical lesions: a clinical research study in Guangxi, China. [Journal Article]
- Eur J Med Res 2016; 21(1):28.
Studies have been reported that cyclin-dependent kinase5 (CDK5) was associated with the development of several cancers. However, the relationship between CDK5 level and clinicopathological factors is still poorly understood in cervical diseases. The aim of the current study was to investigate the expression of CDK5 and its clinical significance in variant cervical lesions.Immunohistochemistry (IHC) was used to detect CDK5 expression in 54 cases of chronic cervicitis, 42 cases of condyloma acuminate (CA), 38 cases of carcinoma in situ, and 360 cases of cervical cancers [adenocarcinoma, n = 63; squamous cell carcinoma (SCC), n = 263; adenosquamous carcinoma, n = 34]. The clinicopathological characteristics in relation to CDK5 were examined by Pearson's Chi-square test.The positive rates of CDK5 were 27.8, 31.0, 50, 54.0, 58.8, and 62.7 % in chronic cervicitis, CA, carcinoma in situ, adenocarcinoma, adenosquamous carcinoma and SCC, respectively. Statistically analysis showed that CDK5 expression in cervical cancer tissues was higher than non-cervical cancer tissues (inflammation and CA) (P < 0.001). The overexpression of CDK5 was significantly correlated with lymph node metastasis (r = 0.317; P < 0.001), histological type (r = 0.198; P < 0.001), FIGO stage (r = 0.358; P < 0.001), TNM stage (r = 0.329; P < 0.001) and pathological grade (r = 0.259; P < 0.001) in cervical lesions evaluated by Pearson's Chi-square test. Furthermore, the positive relationships were found between CDK5 and lymph node metastasis (P < 0.001), FIGO stage (P < 0.001), TNM stage (P < 0.001) and pathological grade (P < 0.001) in SCC. CDK5 was positively interrelated to TNM stage (P = 0.017) in adenosquamous carcinoma.CDK5 may play a vital role in the development of cervical cancer, which may be a marker for the diagnosis, therapy and prognosis of cervical cancer.
- Modified Hughes procedure for reconstruction of large full-thickness lower eyelid defects following tumor resection. [Journal Article]
- Eur J Med Res 2016; 21(1):27.
Tarsoconjunctival flap advancement, or the Hughes procedure, is among the techniques of choice for reconstructing full-thickness lower eyelid defects so as to restore normal anatomy and function with the best possible cosmetic outcome. The purpose of this study is to report the outcome of a series of patients treated with a modified Hughes procedure following malignant tumor removal.This retrospective study included 45 consecutive cases of modified Hughes procedures performed between January 2013 and October 2015. During Hughes flap creation an incisional plane was chosen in all cases, which left Müller's muscle attached to the superior tarsal margin, while disinserting the levator aponeurosis. All cases were grouped according to the horizontal length of the lower lid defect to be reconstructed, as well as to the type of anterior lamella reconstruction (free graft vs. inferiorly based advancement flap). Grouped data were compared for the rate of surgical success, defined as achievement of normal lid function and satisfactory cosmesis without needing further surgical interventions, and for the frequency of specific complications.Surgical success was achieved in 39 cases (87 %). The remaining cases required additional surgery for minor complications including lower-lid ectropion (4 %), pyogenic granuloma (4 %), or lower lid margin hypertrophy (2 %). Donor-site complications were not detected apart from one case of mild entropion with focal trichiasis. No case of premature flap rupture was seen. Neither the horizontal length of the lower lid defect (p = 0.489), nor the type of anterior lamella reconstruction (p = 0.349) significantly affected the surgical success. Particularly, there was no increased onset of lower-lid ectropion among patients receiving an advancement flap.The modified Hughes procedure remains a well-suited technique for reconstructing lower eyelid defects involving up to 100 % of the horizontal lid length. Leaving Müller's muscle attached to the Hughes flap might prevent premature flap dehiscence without increasing the frequency of upper lid retractions in turn. Whether using a free skin graft or a skin-muscle advancement flap for anterior lamella reconstruction, seems to be insignificant for the functional-aesthetical outcome.
- HDAC inhibition activates the apoptosome via Apaf1 upregulation in hepatocellular carcinoma. [Journal Article]
- Eur J Med Res 2016; 21(1):26.
Histone deacetylation, a common hallmark in malignant tumors, strongly alters the transcription of genes involved in the control of proliferation, cell survival, differentiation and genetic stability. We have previously shown that HDAC1, HDAC2, and HDAC3 (HDAC1-3) genes encoding histone deacetylases 1-3 are upregulated in primary human hepatocellular carcinoma (HCC). The aim of this study was to characterize the functional effects of HDAC1-3 downregulation and to identify functionally important target genes of histone deacetylation in HCC.Therefore, HCC cell lines were treated with the histone deacetylase inhibitor (HDACi) trichostatin A and by siRNA-knockdown of HDAC1-3. Differentially expressed mRNAs were identified after siRNA-knockdown of HDAC1-3 using mRNA expression profiling. Findings were validated after siRNA-mediated silencing of HDAC1-3 using qRTPCR and Western blotting assays.mRNA profiling identified apoptotic protease-activating factor 1 (Apaf1) to be significantly upregulated after HDAC inhibition (HLE siRNA#1/siRNA#2 p < 0.05, HLF siRNA#1/siRNA#2 p < 0.05). As a component of the apoptosome, a caspase-activating complex, Apaf1 plays a central role in the mitochondrial caspase activation pathway of apoptosis. Using annexin V, a significant increase in apoptosis could also be shown in HLE (siRNA #1 p = 0.0034) and HLF after siRNA against HDAC1-3 (Fig. 3a, b). In parallel, caspase-9 activity was increased after siRNA-knockdown of HDAC1-3 leading to enhanced apoptosis after HDAC inhibition (Fig. 3c, d).The present data show that siRNA-knockdown of HDAC1-3 plays a major role in mediating apoptotic response to HDAC inhibitors through regulation of Apaf1.
- sMICA as novel and early predictors for acute myocardial infarction. [Journal Article]
- Eur J Med Res 2016; 21(1):25.
MHC class I polypeptide-related chain A (MICA) molecule is induced in response to viral infection, various types of stress, such as endoplasmic reticulum stress, and ischemia or/and reperfusion, by which MICA was shed from the cell surface into the extracellular domain, generating a soluble form (sMICA). In the present study, we designed to investigate the serum sMICA level in patients with AMI and determine whether sMICA could be an early biomarker for diagnosis of AMI.There were 103 patients who presented with first-time AMI that was assessed after the incident. The control group consisted of 103 healthy volunteers. Serum levels of sMICA and Troponin T were detected by the specific ELISA kits.Serum levels of sMICA reach the peaks [(1.34 ± .18 and 1.72 ± .20)n/l] at 6-12 h and serum levels of cTnT reach the peaks [(1.16 ± .28 and 1.14 ± .34)n/l] at 12-24 h. Both of them were significantly higher than the healthy controls [(.168 ± .014) n/l, p = .000] for sMICA and [(.13 ± .06) n/l, p = .000] for Troponin T (cTnT). sMICA is more sensitive in the early diagnosis of AMI than cTnT. The combined ROC analysis revealed an AUC value of .78 (95 % CI .69-.83) in discriminating AMI patients from healthy controls.We have detected high levels of sMICA in patients with AMI. Elevated serum sMICA may be a novel biomarker for the early detection of myocardial injury in humans.
- Breast reconstruction after neoadjuvant radio chemotherapy: review and personal technique IDEAL concept REV-EJMR-D-15-00268. [Journal Article, Review]
- Eur J Med Res 2016; 21(1):24.
Neoadjuvant radio chemotherapy and immediate reconstruction for breast cancer are still under debate. But there are recent abstracts and articles which show that neoadjuvant radio chemotherapy is feasible and could improve the clinical outcome of breast cancer patients. The aim of this review is to present the authors' techniques and approaches with regard to neoadjuvant radiation of breast cancer patients. It seems that the concept of immediate implant delayed autologous breast reconstruction could be a safe procedure that is at least equivalent to primary autologous reconstruction.