Endometrium receptivity in premature ovarian insufficiency – how to improve fertility rate and predict diseases?

Abstract

More empathized approach is required and is obligatory to women with premature ovarian insufficiency (POI) interested for pregnancy. In order to improve fertility rate in POI patients our suggestions would be: (1) To decrease FSH value to 10–15?IU/L by increasing estrogen. Oocyte donation can be suggested after a minimum of six month interval from FSH between 10–15?IU/L and when no dominant follicles are found. (2) To perform oral glucose tolerance test (OGTT). Insulin sensitizing agents has to be included, when indicated, 3–6?month before pregnancy. (3) TSH has to be 1–2.5?mM/L during 3–6?months before pregnancy. (4) Tests for thrombophyllia (Leiden V, FII, MTHFR, PAI) have to be obligatory. They are less expensive than those repeated in vitro fertilizations. Therapy has to be included according to the indications. (5) In order to regulate disturbed immune response in POI patients with endometriosis oral contraceptive therapy is needed for atleast six months prior to the pregnancy. (5) Encourage the patients and advice them about healthy life style and eating habits. (6) Add other drugs, when they are indicated. Complex interplay between endocrine, immunological, haematological, and psychological factors are very often underdetected in POI patients. It is very important to find out the real time for oocyte donation after correcting all the disturbances, improving endometrium receptivity and reaching women’s acceptable psychological status. Untreated disturbances induce cardiovascular diseases, diabetes mellitus, thyroid diseases, coagulopathioes etc.     

Maternal plasma interleukin-6, interleukin-1β and C-reactive protein as indicators of tocolysis failure and neonatal outcome after preterm delivery

Objective. To investigate whether maternal serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and high sensitive C-reactive protein (CRP) could be used as markers of tocolysis failure and adverse neonatal outcome in pregnancies with preterm labor (PL).

Methods. Forty-seven maternal blood samples taken because of PL at admission and delivery were analyzed. Control samples were taken from 20 gravidas with normal pregnancies. Differences in interleukins and CRP levels with or without chorioamnionitis, connatal infection or periventricular leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of tocolysis failure and adverse neonatal outcome.

Results. All three parameters were significantly higher in patients delivering prematurely than in patients delivering at term. All three parameters were significantly higher with than without histologic chorioamnionitis (p < 0.001), with than without connatal infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1β, p < 0.05 for CRP), and in pregnancies with preterm premature rupture of membranes (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01). Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood admission concentrations for neonatal PVL, resulted in sensitivity of 81% and specificity of 91% and sensitivity of 91% and specificity of 81%, respectively. At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and 8.9 of CRP, both parameters were effective predictors of connatal infection.

Conclusions. Maternal blood IL-6 and CRP could become useful in predicting tocolysis failure and intrauterine treat for the fetus.     

Air gun injury with deadly aftermath – Case report

In Republic of Macedonia the use of air guns is quite widespread. They are used mainly for target practice. They are regulated by the Law of Arms, where they are defined as pneumatic weapons. There is no legal limit on type or quantity of ammunition that one may possess. Our Institute performs at least 90% of the forensic autopsies in Macedonia. In this report we describe the only fatality by pneumatic weapon to come to our attention over the past 10 years. A 6-year-old girl was accidentally wounded by her brother when he and his father were trying a new air gun, a 4.5 mm single shot, break barrel, spring piston air rifle manufactured in China under the brand “Westlake”. She died within minutes. Autopsy showed cardiac tamponade due to penetration of the aorta. A 0.5 g metal projectile, 4.5 mm in diameter, with a pointed, conical shape, was recovered from the pericardial sac.     

Clinical outcome of early glottic carcinoma in Serbia

Objective

Proposed methods for treating early glottic carcinoma are cordectomy through laryngofissure, laser cordectomy, and radiotherapy. The aim of the study was to conduct comprehensive study to evaluate oncological and functional results of different treatment modalities for Tis and T1 glottic carcinoma, identify prognostic factors for the outcome of treatment and decide where we stand in applying worldwide standards of early glottic carcinoma treatment.

Methods

Prospective study was conducted on 221 patients treated with Tis and T1 glottic carcinoma from 1998 to 2003 (72 patients were treated endoscopically with CO₂ laser, 75 patients with cordectomy through laryngofissure and 74 with radiotherapy), with follow-up period from 38 to 107 months. Important demographic and clinical variables were analyzed. Voice quality after the treatment was assessed using multidimensional voice analysis.

Results

Comparing oncological results of three modalities of treatment, there were no significant differences. Functional results of treatment were better after laser cordectomy and primary radiotherapy than following the open cordectomy. Five-year survival rate was almost identical in all three groups of patients, and important prognostic factors for survival were age and histological grade of the tumor.

Conclusion

Considering that the choice of treatment in our country is also greatly influenced by other paramedical factors, such as distance from treatment facility, reliability of follow-up, significant time delay of radiotherapy because of small number of radiology centers and strong patients’ surgeon and treatment preference, we consider endoscopic laser surgery highly efficient and preferred choice of treatment for early glottic carcinoma.     

Association of interleukin-10, tumor necrosis factor-α and transforming growth factor-β gene polymorphisms with the outcome of diffuse large B-cell lymphomas

Background

Published data indicate that common genetic variants in immune/inflammatory response genes can affect the outcome of diffuse large B-cell lymphomas (DLBCL). This study investigated the association of interleukin (IL)-10 (?3575, ?1082), tumor necrosis factor (TNF)-α ?308 and transforming growth factor (TGF)-β Leu10Pro gene polymorphisms with clinical characteristics and outcome of DLBCL patients treated with rituximab–CHOP therapy.

Methods

Between January 2004 and December 2007, a total of 84 patients with newly diagnosed DLBCL entered into this study. Genotypes were determined with PCR-based methodology.

Results

Patients presenting with B symptoms had IL-10 ?3575 TA/AA genotypes more frequently than TT genotype [odds ratio (OR) 2.89, 95 % confidence interval (CI) 1.11–7.57; p = 0.03]. Carriers of TGF-β Pro10 allele more frequently had an advanced clinical stage III/IV (OR 4.65, 95 % CI 1.33–16.19; p = 0.016) and intermediate-high/high IPI score (OR 5.37, 95 % CI 1.45–20.0; p = 0.012). In rituximab–CHOP-treated patients (n = 64), the TNF-α ?308 AG/AA carriers had shorter overall (p = 0.048) and event-free survival (p = 0.07) compared to GG carriers. In multivariate analysis of prognostic factors for survival, the TNF-α AG/AA genotypes were significantly associated with inferior survival of lymphoma patients (OR 0.23, 95 % CI 0.07–0.78; p = 0.018).

Conclusion

Our results indicate the association of IL-10 ?3575 and TGF-β Leu10Pro gene variations with clinical characteristics. In patients treated with rituximab–CHOP therapy, the TNF-α ?308 AG/AA genotypes showed a significantly less favorable survival than the GG genotype.     

Combining rules and machine learning for extraction of temporal expressions and events from clinical narratives

Objective

Identification of clinical events (eg, problems, tests, treatments) and associated temporal expressions (eg, dates and times) are key tasks in extracting and managing data from electronic health records. As part of the i2b2 2012 Natural Language Processing for Clinical Data challenge, we developed and evaluated a system to automatically extract temporal expressions and events from clinical narratives. The extracted temporal expressions were additionally normalized by assigning type, value, and modifier.

Materials and methods

The system combines rule-based and machine learning approaches that rely on morphological, lexical, syntactic, semantic, and domain-specific features. Rule-based components were designed to handle the recognition and normalization of temporal expressions, while conditional random fields models were trained for event and temporal recognition.

Results

The system achieved micro F scores of 90% for the extraction of temporal expressions and 87% for clinical event extraction. The normalization component for temporal expressions achieved accuracies of 84.73% (expression''s type), 70.44% (value), and 82.75% (modifier).

Discussion

Compared to the initial agreement between human annotators (87–89%), the system provided comparable performance for both event and temporal expression mining. While (lenient) identification of such mentions is achievable, finding the exact boundaries proved challenging.

Conclusions

The system provides a state-of-the-art method that can be used to support automated identification of mentions of clinical events and temporal expressions in narratives either to support the manual review process or as a part of a large-scale processing of electronic health databases.     

A novel regulator of angiogenesis in endothelial cells: 5-hydroxytriptamine 4 receptor

The 5-hydroxytryptamine type 4 receptor (5-HT₄R) regulates many physiological processes, including learning and memory, cognition, and gastrointestinal motility. Little is known about its role in angiogenesis. Using mouse hindlimb ischemia model of angiogenesis, we observed a significant reduction of limb blood flow recovery 14 days after ischemia and a decrease in density of CD31-positive vessels in adductor muscles in 5-HT₄R^?/? mice compared to wild type littermates. Our in vitro data indicated that 5-HT₄R endogenously expressed in endothelial cells (ECs) may promote angiogenesis. Inhibition of the receptor with 5-HT₄R antagonist RS 39604 reduced EC capillary tube formation in the reconstituted basement membrane. Using Boyden chamber migration assay and wound healing ??scratch?? assay, we demonstrated that RS 39604 treatment significantly suppressed EC migration. Transendothelial resistance measurement and immunofluorescence analysis showed that a 5-HT₄R agonist RS 67333 led to an increase in endothelial permeability, actin stress fiber and interendothelial gap formation. Importantly, we provided the evidence that 5-HT₄R-regulated EC migration may be mediated by G??13 and RhoA. Our results suggest a prominent role of 5-HT₄R in promoting angiogenesis and identify 5-HT₄R as a potential therapeutic target for modulating angiogenesis under pathological conditions.