Current state of knowledge on oral anticoagulant reversal using procoagulant factors.

OBJECTIVE: To discuss current trends and challenges in the use of procoagulants for treating bleeding caused by use of oral anticoagulants. DATA SOURCES: Literature searches of PubMed (MEDLINE), Google, and Medscape were conducted in February 2013. There were no date limitations. Search terms included anticoagulation agents, anticoagulation reversal, anticoagulation reversal agents, apixaban, clinical studies, dabigatran, 3-factor PCCs, 4-factor PCCs, FEIBA, fresh frozen plasma, human studies, pharmacology, prescribing information, rFVIIa, rivaroxaban, vitamin K, and warfarin. DATA SYNTHESIS: Warfarin has been the mainstay for the treatment and prevention of primary and secondary thrombosis in patients with cardiovascular dis orders such as atrial fibrillation, deep vein thrombosis, pulmonary embolism, and stroke. Three oral anticoagulants have recently become available in the US: a direct thrombin inhibitor, dabigatran etexilate, and 2 direct factor Xa inhibitors, rivaroxaban and apixaban. Reversal strategies for anticoagulant-associated bleeding are well established for warfarin; however, strategies to stop bleeding in a patient who has taken one of the newer anticoagulants are less clear. In the US, agents available for oral anticoagulant reversal include activated prothrombin complex concentrate (APCC), 3-factor PCCs, and recombinant activated factor VII (rFVIIa). Few studies have evaluated the 3-factor PCCs, and current evidence for APCC and rFVIIa as reversal agents for dabigatran and rivaroxaban is based primarily on laboratory or animal studies, or on small studies in healthy humans and case reports. CONCLUSIONS: Patients contemplating using the new oral anticoagulants should be informed about specific clinical situations that could pose a bleeding risk such as the need for emergency surgery because no reliable antidote is available to stop the bleeding, which could prove fatal.

[Prenatal diagnosis of fetal chromosomal aneuploidies using quantitative fluorescent PCR (QF-PCR)]. / Wykorzystanie ilosciowej fluorescencyjnej techniki PCR (QF-PCR) w diagnozowaniu wybranych aneuploidii chromosomowych u plodu.

The trisomy of the 21 chromosomes is one of the most important chromosomal anomalies and is responsible for Down syndrome. It persists in Poland in 1/700 birth. The risk of childbirth with Down syndrome grows with age, especially in women after 35 years old. In this study we performed QF-PCR method with specific polymorphic sequence--D21S11 for detection of trisomy of the 21 chromosome. DNA for PCR was isolated from amniotic fluid, blood of healthy and with Down syndrome patients. PCR was performed with ProfilerPlus Kit, which permits for amplification of 9 STR loci (also D21S11) and gender marker--amelogenin gene. We detected incorrect amplification of STR sequence for D21S11 in one amniotic fluid, which was confirmed by kariotyping as trisomy of the 21 chromosome of fetus.

[Analysis of correlation between HPV DNA lymph node presence and pathologic parameters of primary tumour in cervical carcinoma patients treated surgically]. / Ocena korelacji obecnosci DNA HPV w wezlach chlonnych chorych na raka szyjki macicy z parametrami histopatologicznymi w zmianie pierwotnej.

Young-age sexual activity, multiple sexual partners, number of pregnancies, smoking and human papilliomavirus (HPV) infections are factors commonly considered as promoters of cervical tumorogenesis. Cervical carcinoma patients' prognosis correlates significantly with staging (according to FIGO classification). In early stages lymph-node involvement is considered as the most important prognostic factor. Other factors are: initial volume of the lesion, lymphatic and blood vessels involvement, depth of cervical invasion. Also parametrium involvement seems to decrease the rate of 5-year survival. The aim of the research was to estimate correlation between HPV DNA lymph node presence and pathologic parameters of primary tumour in surgically treated cervical carcinoma patients. We analysed DNA isolated from lymph nodes sampled intra-operatively from 134 patients, surgically treated for cervical cancer with PCR. We confirmed the presence of HPV DNA sequences in lymph nodes in 81 (60.5%) cases. Lymph node presence of HPV DNA rate was significantly higher in: advanced tumours, cases with initial lesion volume exceeding 10 cm3, cases with uterus and vaginal involvement and with initial tumour invasion deeper than 10 mm.

Fluticasone or montelukast in preschool wheeze: a randomized controlled trial.

INTRODUCTION: Approximately 30% of children younger than 3 years experience at least 1 episode of wheezing. Antiasthmatic medication is routinely prescribed, but its effectiveness remains unclear. Our study was aimed to evaluate the effect of anti-inflammatory treatment on frequency and severity of preschool wheeze episodes (PWEs). METHODS: Children aged 6 to 36 months with the first up to the third PWE were randomly assigned to receive montelukast, fluticasone, or no treatment for 12 weeks. The outcome measures were the number of PWEs, the number of hospitalizations due to PWE, and the severity of respiratory symptoms. results: There were no significant differences in outcome measures between the groups. However, tobacco-exposed children treated with fluticasone had significantly fewer PWEs (P = .01). CONCLUSION: Neither montelukast nor fluticasone has proven effective in the prevention of PWE recurrence. Children of smoking parents may benefit from fluticasone treatment after PWE. This observation requires confirmation in larger studies.

[The incidence of human papilloma virus (HPV) DNA in patients with cervical carcinoma from Gdansk region]. / Wystepowanie dna wirusa hpv u pacjentek z rakiem szyjki macicy w regionie gdanskim.

OBJECTIVES: We have estimated the incidence of human papilloma virus (HPV) DNA in cervical smears of patients with cervical carcinoma, treated in 1997-1998 at the II Department of Obstetrics and Gynecology, Medical University of Gdansk, Poland. MATERIALS AND METHODS: We have examined 107 patients suffering from cervical cancer. The HPV DNA was detected with the polymerase chain reaction (PCR) method using two primer pairs located in the E6, E7 open reading frames. HPV typing was executed by restriction fragments length polymorphism PCR (RFLP-PCR) method. RESULTS: HPV DNA was detected in 75 (70.1%) patients. A group of patients with Ib (43%) and IIa (19.6%) clinical degrees made the highest percentage within the research group. We found no statistically significant differences between various clinical degrees of cervical cancer in the group of patients both HPV positive and negative. CONCLUSIONS: The frequency of HPV especially HPV 16 type infection incidence in cervical carcinoma is lower in Gdansk region than currently published.

[HPV 16 DNA occurrence in lymph nodes of patients with cervical carcinoma]. / Wystepowanie DNA wirusa HPV 16 w przerzutach do wezlówa chlonnych u chorych na raka szyjki macicy.

OBJECTIVES: We estimated the occurrence of DNA HPV 16 presence in lymph nodes of 25 patients undergoing abdominal operation for cervical carcinoma. MATERIALS AND METHODS: The presence of HPV 16 DNA was detected during the preoperative diagnosis procedure by the PCR method. RESULTS: According to the histopathological examination, metastases in the lymph nodes were present in material from two patients. It was confirmed HPV 16 DNA was detected with PCP. We found also 6 patients with HPV 16 DNA in their lymph nodes without histological confirmation. CONCLUSIONS: We consider PCR detection of HPV DNA as a simple and useful support of pathology diagnosis.

Predictive value of HPV DNA in lymph nodes in surgically treated cervical carcinoma patients--a prospective study.

OBJECTIVE: High-risk types of HPV are etiological factors in cervical cancer. Lymph node involvement in cervical cancer patients reduces 5-year survival rates by 25-60%. However, the influence on survival of HPV DNA positivity in histopathologically negative lymph nodes remains unresolved. METHODS: The study included 116 of 148 patients who underwent Piver type III radical hysterectomy and pelvic lymphadenectomy and who showed HPV DNA positivity in the primary lesion. Lymph node tissues were tested for the presence of HPV DNA, using a PCR technique. RESULTS: We found the presence of HPV DNA sequences in lymph nodes dissected intraoperatively in 81 (69.83%) cases. In analysis, we compared patients from 3 groups: HPV- and metastatic-negative (LN HPV-M-); HPV-positive metastatic-negative (LN HPV+M-); and metastatic-positive (LN M+). We discovered that survival in groups LN M+ and LN HPV+M- did not differ statistically (p=0.37). However, the survival periods in these two groups differed when compared with LN HPV-M- patients (p<0.001). Using Cox's proportional hazards model, we found that the presence of lymph node HPV DNA, and FIGO stage, and primary lesion volume were independent parameters correlating with survival and mortality risk. CONCLUSION: We conclude that the presence of HPV DNA in lymph nodes is an early sign of metastasis and should be treated as such in prognostic outlook and planning the therapeutic strategy.

Human papillomavirus type 16 status in cervical carcinoma cell DNA assayed by multiplex PCR.

Integration of human papillomavirus (HPV) DNA into host genome occurs early in cancer development and is probably an important event in malignant transformation of cervical cancer. The HPV genome integration usually disrupts E2 gene open reading frames. It results in the lack of E2 gene suppressor of the synthesis of E6 and E7 products which, in turn, leads to the overexpression of E6 and E7 genes. The oncogenic HPV types (HPV16, -18, -45, and -58) can be present as episomes or may integrate into human chromosomes. Sixty-six cervical cancer patients positive for HPV16 were tested for the presence of E6, E2, E1, and L1 genes. Multiplex PCR was carried out in all cases. Using cluster analysis, the calculated ratios of E1/E6, E2/E6, L1/E6, E1/E2, and E2/(E1*E6) gene amplification products were divided into two or three statistically different groups. These were used for statistical analysis of the prevalence of specific gene types in histological types of cancer, different levels of clinical staging, and histologically confirmed nodal metastases. The statistical analysis proved a significant correlation in the ratios of E2/E6 and E1/E2 only. The E2/E6 and E1/E2 were higher in carcinoma in situ than in advanced squamous cancers. The E2/E6 ratios were lower in higher clinical stages. The multiplex PCR estimation of the E2/E6 ratio could be a simple method for selecting patients with a high risk of a poor outcome in a standard stage-dependent treatment procedure.