Publications by authors named "Anna Knafel"

28 Publications

  • Page 1 of 1

"Y Sign" at the Level of the 3-Vessel and Trachea View: An Effective Fetal Marker of Aortic Dextroposition Anomalies in the First Trimester.

J Ultrasound Med 2018 Aug 27;37(8):1869-1880. Epub 2017 Dec 27.

Dobreusg Ultrasound Group Practice, Krakow, Poland.

Objectives: The "Y sign" at the level of the 3-vessel and trachea view corresponds to thinning of main pulmonary artery and arterial duct and a dilated transverse aortic arch. The purpose of this study was to evaluate the Y sign for the diagnosis of aortic dextroposition anomalies at the time of the first-trimester scan and to assess the screening performance of only the Y sign, only abnormal left axis deviation (axis sign), and their combination for the diagnosis of aortic dextroposition anomalies.

Methods: A prospective evaluation of 6025 pregnant women undergoing first-trimester ultrasonography was conducted. The cardiac axis was measured in all examined patients and considered abnormal (positive axis sign) at greater than 57 °. The frequency of the Y sign and the axis sign was assessed for this population, and their screening performance for the diagnosis of aortic dextroposition anomalies was calculated.

Results: A total of 5775 patients fulfilled the inclusion criteria. Aortic dextroposition anomalies were diagnosed in 17 cases (tetralogy of Fallot in 8 and Fallot-like double-outlet right ventricle in 9). The Y sign was found in 18 of 5775 (0.3%) fetuses examined, of which 7 of 18 were confirmed with tetralogy of Fallot, 9 of 18 with a Fallot-like double-outlet right ventricle, and 2 of 18 with pulmonary stenosis. A positive axis sign of greater than 57 ° was found in 20 fetuses, including 4 with normal heart anatomy. The sensitivity values of the Y sign, the axis sign, and their combination were 94%, 76%, and 94%, respectively.

Conclusions: Visualization of the Y sign should increase the suspicion of aortic dextroposition anomalies in the late first trimester. The screening performance of the Y sign alone and in combination with an abnormal cardiac axis was high and may aid in the early diagnosis of aortic dextroposition anomalies in the fetus.
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August 2018

The significance of a prenatal diagnosis of right aortic arch.

Prenat Diagn 2017 Apr 13;37(4):365-374. Epub 2017 Mar 13.

Department of Obstetrics and Perinatology, Jagiellonian University Medical College, Kraków, Poland.

Objectives: To analyze a population of fetuses with prenatally diagnosed right aortic arch (RAA).

Methods: Retrospective study of fetuses with RAA diagnosed prenatally between 2011 and 2015 in two referral centers.

Results: Right aortic arch was found in 4.4% (46/1036) of fetuses with cardiovascular abnormalities (CVA). As an isolated anomaly, RAA was present in 30.4% of cases; in 32.6%, other CVA were detected; in 23.9%, CVA and extracardiac anomalies; and in 13.1%, only extracardiac malformations. The most common noncardiac abnormalities were thymus hypoplasia/aplasia (7/17), of which six had deletion 22q.11.2. In another three fetuses, trisomy 21 was present. One intrauterine fetal death occurred at 41 weeks of pregnancy, and two fetuses died after birth. In six of 18 infants with known follow-up, symptoms of dysphagia were reported, of which four infants underwent surgical intervention. In 12 infants, an isolated RAA was clinically silent.

Conclusions: The diagnosis of RAA is an indication for a detailed examination of cardiac and noncardiac structures, including the thymus. It is advisable to consider genetic testing, together with the assessment of deletion 22q11.2, especially in the case of accompanying defects. The prognosis depends on underlying cardiac and extracardiac anomalies and possibly coexisting genetic defects. Isolated anomalies are asymptomatic. © 2017 John Wiley & Sons, Ltd.
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April 2017

Ultrasound evaluation of inferior facial angle (IFA) in a population of normal fetuses at 11-13 weeks (+6 days) gestation.

Przegl Lek 2017;74(1):8-12

Retrognathia is a common feature of many fetal anomalies that may be diagnosed during ultrasound examination. The most common method used for the diagnosis of this condition is the inferior facial angle (IFA). The existing reference ranges for IFA have been established for the fetuses at 18- 28 weeks gestation and may be not applicable in the first trimester. The aim of the study was to document changes of IFA from 11+0 to 13+6 weeks gestation, to verify the reproducibility of IFA calculations obtained by the same examiner and to investigate the possible association between IFA values at the first and second trimester scans.

Material And Methods: A prospective study was performed in 512 singleton pregnancies during the first trimester ultrasound exam. IFA was calculated by measuring the angle made by the cross-section of a line orthogonal to the forehead at the level of nasofrontal suture and the line from the tip of the mentum to the anterior border of the more protrusive lip. In 100 cases, stored images were used to calculate IFA twice by the same examiner. In a second trimester scan, IFA was measured again in 215 fetuses.

Results: The median IFA value at the time of the first trimester (IFA-1) was 880 (IQR: 8.0) and decreased with crown-rump length (CRL) and biparietal diameter (BPD). A moderate negative correlation was shown between IFA-1 and CRL (r= 0.3; p<0.001) as well as between IFA-1 and BPD-1 (r= 0.176; p=0.010). An intraclass correlation coefficient (ICC) of 0.87 (95% CI: 0.81 – 0.91) confirmed strong intraobserver agreement between two IFA measurements. In 215 fetuses that underwent a second trimester screening, the median IFA-2 was significantly lower compared to IFA-1(215) (750; IQR: 10.0 vs.870; IQR: 8.0; p<0.001), and there was no correlation between IFA1215 and IFA-2 (r= -0.024; p=0.731).

Conclusions: In the first trimester, IFA decreases with CRL and BPD. When performed by the same operator, measurement of IFA is reproducible. There is no correlation between the IFA values in the first and second trimesters.
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June 2018

Age at natural menopause in women on long-term methotrexate therapy for rheumatoid arthritis.

Menopause 2016 10;23(10):1130-8

1Department of Gynecology and Oncology, Jagiellonian University Medical College, Krakow, Poland2Center of Rheumatology, Immunology and Rehabilitation, Dietl Specialistic Hospital, Krakow, Poland3Department of Public Health, Medical University of Warsaw, Warsaw, Poland4Department of Gynecological Endocrinology, Jagiellonian University Medical College, Krakow, Poland.

Objective: The aim of the study was to compare the natural menopause ages of healthy women with those of women with methotrexate (MTX)-treated rheumatoid arthritis (RA), and to specifically assess the effect of disease onset and activity and the use of MTX on the age of the last menstruation.

Methods: We performed a retrospective review of medical records to identify the ages at which menopause occurred in women with premenopausal RA treated with MTX and in women with postmenopausal onset, irrespective of therapy. Natural menopause ages were also compared between participants with and without RA.

Results: Women with premenopausal onset of RA underwent menopause at a significantly younger age than did healthy women (P < 0.001) or those with postmenopausal disease onset (P = 0.001). Menopause also occurred at younger ages in participants with postmenopausal disease onset than in healthy controls (P = 0.012). The study suggested that menopause age was positively correlated with the age at which RA was diagnosed (R = 0.51; P < 0.001) in women with premenopausal RA onset, but was independent of the participant's age at menarche, number of pregnancies, or MTX therapy. Participants with RA onset at ≤ 35 years of age had a ninefold higher risk of premature menopause (P = 0.008).

Conclusions: The age at which menopause occurs in a patient with RA depends on the patient's age at the time of disease onset and its duration, but is not influenced by MTX treatment.
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October 2016

Screening for trisomy 18 using traditional combined screening vs. ultrasound-based protocol in tertiary center environment.

J Matern Fetal Neonatal Med 2017 Aug 5;30(15):1765-1770. Epub 2016 Sep 5.

f St. Lucas Obstetric Center , Czestochowa , Poland.

Objectives: To compare the screening performances of combined screening test risk algorithm for trisomy 18 (T18) using various cutoffs with a multiparameter ultrasound-based method. To compare the general and maternal age (MA)-based screening performances for T18 by means of combined screening and an ultrasound-based method.

Methods: This was a prospective, multicenter study based on a mixed-risk non-selected population of women referred to referral centers for a first-trimester screening. Each subject was offered a choice between either a traditional combined screening (CSG arm) or an ultrasound-based screening (USG arm). General and MA-based screening performances were measured.

Results: The study population comprised 10 820 pregnancies as follows: 5132 in the CSG arm, including 28 cases of T18, and 5688 in the USG arm, including 29 cases of T18. In the CSG arm, the detection rate (DR) for T18 at a false-positive rate (FPR) of 3% was 86%, whereas the DR was 100% for the USG arm. MA influenced the T18 screening performance in the CSG arm and reduced the DR in MA ranges  <26 years and 31-35 years. This influence was not observed in the USG arm.

Conclusions: Only, a multiparameter ultrasound-based screening method may be considered an effective alternative to combined screening for T18 screening. The technique exhibits high and stable DRs irrespective of MA.
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August 2017

What are the most common first-trimester ultrasound findings in cases of Turner syndrome?

J Matern Fetal Neonatal Med 2017 Jul 29;30(13):1632-1636. Epub 2016 Aug 29.

a Department of Gynecology and Obstetrics , Jagiellonian University , Krakow , Poland.

Objectives: To identify the most common first-trimester ultrasound findings in Turner syndrome (TS). To evaluate which first-trimester findings can be best used to predict the likelihood of TS.

Methods: This was a prospective study, based on singleton pregnancies. The referrals included 6210 patients. Scan protocol covered a review of the early fetal anatomy and markers of aneuploidy.

Results: Study population comprised 5644 pregnancies: 5613 with a normal karyotype and 31 cases of TS. Statistically significant differences (p < 0.05) were found between euploidy and TS groups in terms of nuchal translucency (NT; 1.7 mm versus 8.8 mm) and fetal heart rate (FHR; 160 versus 171 beats per minute). None of the TS cases demonstrated absent markers of aneuploidy as opposed to 5133 (91.4%) cases of euploidy. NT and abnormal DV flow (aDV or revDV) were the most common markers found in combination in TS cases (n = 17; 54.8%). 27 (0.5%) cases of euploidy and 17 (54.8%) cases of TS revealed congenital heart defects. Fetal hydrops was observed in 14 cases of TS (43.8%) and in 5 of euploidy (0.1%). In backward regression model, NT > 3.5 mm and right dominant heart (RDH) augmented the risk of TS risk by 991 and 314 times, respectively.

Conclusions: First-trimester sonography is a feasible method to identify the most characteristic features of TS fenotype. When the first-trimester pattern of TS is considered, a highly thickened NT, FHR above the 95th percentile, abnormal ductus venosus velocimetry, fetal hydrops, and RDH should be specifically searched for.
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July 2017

Combined screening test for trisomy 21 - is it as efficient as we believe?

J Perinat Med 2017 Feb;45(2):185-191

Objectives: To compare two first-trimester screening strategies: traditional combined screening and the one based on ultrasound markers only. We investigated the effect of maternal age (MA) on the screening performance of both of these strategies.

Methods: This was a prospective observational study based on a non-selected mixed-risk population of 11,653 women referred for first-trimester screening. The study population was divided in two groups: combined screening (CS) and ultrasound-based screening (US). Absolute risk was calculated to determine the influence of MA on screening performance.

Results: The CS arm comprised 5145 subjects including 51 cases of trisomy 21 (T21), and the US arm comprised 5733 subjects including 87 subjects with T21. Seven hundred and seventy-five subjects were excluded from the study. For a false positive rate (FPR) of 3%, the detection rate (DR) of T21 in CS arm was 78% vs. 90% in US arm. For 5% FPR, DR was 84% and 94% in CS and US arm, respectively. MA had an influence on DR positive rates in CS: both DR and FPR for T21 increased with advance in MA.

Conclusions: The US protocol showed higher DR of T21 compared to the CS one. It may be considered as a viable alternative to CS for T21 where access to biochemical testing is limited.
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February 2017

[Carbon monoxide poisoning in pregnant woman].

Przegl Lek 2015 ;72(9):482-4

Carbon monoxide poisoning is one of the most frequent types of poisoning caused by gases. Exposure of a pregnant woman to carbon monoxide is connected with transmission of this gas to her fetus what may cause oxygen deficiency, and further, the damage to its organs. The article describes a case of carbon monoxide poisoning of a 28-weeks pregnant woman who was treated in a hyperbaric chamber. Therapy was successful and the woman gave birth to a healthy, full term infant. In case of poisoning to a pregnant woman the above seems to be the most advantageous solution.
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April 2016

[The role of cytologic-colposcopic diagnostics in qualification to LEEP (loop electrical excision procedure)].

Przegl Lek 2016;73(7):472-8

Loop electrosurgical excision procedurę (LEEP) is both a diagnostic and a therapeutic method in cervical intraepithelial neoplasia (CIN). The key for the therapeutic effect is accurate diagnostics, in particular precise colposcopic localisation of CIN in the cervical area. It enables localising a lesion highly suspected of neoplasmatic character, excising a sample for histopathologic examination and making a pre-therapeutical diagnosis, as well as choosing optimal way of treatment. Colposcopic examination conducted in 115 women with inapropriate cytologic exam, i.e. HGSIL, revealed CIN-suspected image in all cases. Highly positive and statistically relevant correlation between results of colposcopic examination and histologial examination of samples excised with the use of high frequency electrosurgical loop in examined group was stated. Due to its efficiency, easy implementation, great tolerance and wide acceptance the procedure is widespread.
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May 2018

How Effective Is First-Trimester Screening for Trisomy 21 Based on Ultrasound Only?

Fetal Diagn Ther 2016 19;39(2):105-12. Epub 2015 Aug 19.

Department of Obstetrics and Gynecology, Jagiellonian University, Krakow, Poland.

Objective: To evaluate the most common first-trimester ultrasound features of fetuses with trisomy 21 (T21) and to examine the screening performance for Down syndrome (DS) using only ultrasound-based protocols. To investigate whether maternal age (MA) has an impact on the efficacy of the ultrasound-based screening methods.

Methods: In a prospective study, 6,265 patients were examined. Two ultrasound-based risk calculation protocols were applied: 'NT' (based on nuchal translucency) and 'NT+' (based on NT and secondary markers).

Results: A total of 5,696 patients were enrolled for analysis; 84 subjects with T21 were identified. Combinations of abnormal ultrasound markers were observed in only 1.2% of euploid fetuses compared to 71.5% of fetuses with T21. Among 17.9% of DS cases with cardiac anomaly, 14.3% comprised atrioventricular septal defects. For a false-positive rate of 3%, the detection rates of T21 were 73.8 and 91.7% for the 'NT' and 'NT+' protocols, respectively. The efficacy of both methods was affected by MA.

Conclusions: Most of the fetuses with DS demonstrate a combination of ultrasound markers of aneuploidy in the first trimester. The 'NT+' protocol is efficient and provides comparable performance as a combined screening test. It is a valuable method, especially when the access to biochemical analysis is restricted.
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December 2016

Primary Vulvo-Vaginal Cancers: Trends in Incidence and Mortality in Poland (1999-2012).

Gynecol Obstet Invest 2015 9;80(4):240-5. Epub 2015 Jun 9.

Department of Gynecology and Oncology, Jagiellonian University Medical College, Krakow, Poland.

Background: The aim of this study was to determine the incidence, mortality rates and trends of vulvar and vaginal cancers in Poland.

Methods: Data were retrieved from the Polish National Cancer Registry. Age-standardised rates (ASRs) of cancer incidence and mortality were calculated by direct standardisation, and joinpoint regression was performed to describe the trends using the average annual percent change (AAPC).

Results: From 1999 to 2012, the number of diagnosed cases of vulvar cancer was 5,958, and the ASRs of incidence varied from 0.99 to 1.18, with a significant trend towards a decrease (AAPC -0.78; p < 0.05). The ASR of mortality varied from 0.39 to 0.62, with a slight but insignificant increase in trend (AAPC 0.72; p > 0.05). The ASR of vaginal cancer incidence varied from 0.21 to 0.31, while the ASR of mortality ranged from 0.09 to 0.22. This study also proved a significantly falling trend in vaginal cancer mortality (AAPC -4.69; p < 0.05) and a decreasing trend in vaginal cancer incidence (AAPC -1.67; p > 0.05).

Conclusion: The rarity of vulvar and vaginal cancers as well as the decline in their incidence rates should not discourage further research on the epidemiology and treatment of these conditions.
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September 2016

How effective is ultrasound-based screening for trisomy 18 without the addition of biochemistry at the time of late first trimester?

J Perinat Med 2016 Mar;44(2):149-59

Unlabelled: Trisomy 18 (T18) remains the second most common aneuploidy. It is associated with multiple congenital anomalies and causes intrauterine fetal demise in the most severe cases.

Objectives: To examine the screening performance of ultrasound-based protocols for detecting T18, we aimed to determine the most common signs and their prevalence in fetuses with T18 to develop logistic regression model.

Methods: This was a prospective study based on singleton pregnancies examined at gestation 11+0 to 13+6. The referrals constituted 6210 patients. Scan protocol enclosed a systematic review of the entire early fetal anatomy, including fetal cardiac evaluation and sonographic signs of aneuploidy.

Results: Our study population comprised 5650 pregnancies: 5613 cases with a normal karyotype and 37 cases with T18. The mean nuchal translucency (NT) thickness in the subgroup of euploidy was 1.7 and in the subgroup of T18 it was 5.4. No statistically significant differences were found in terms of maternal age. One case of T18 (2.7%) demonstrated no markers of aneuploidy as opposed to 5111 cases of euploidy (91.1%). Extracardiac malformations were identified in 13 cases of T18 (35.1%) and in 48 cases of euploidy (0.8%). Congenital heart defects were observed in 26 cases of T18 (70.3%) and in 27 cases of euploidy (0.5%).

Conclusions: Our results showed good screening performance of ultrasound-based risk calculation models. When the first trimester pattern of T18 is considered, an increased NT, tricuspid regurgitation, single umbilical artery, omphalocele and right dominant heart should be specifically searched for.
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March 2016

Prenatal detection of congenital heart defects at the 11- to 13-week scan using a simple color Doppler protocol including the 4-chamber and 3-vessel and trachea views.

J Ultrasound Med 2015 Apr;34(4):585-94

Chair of Gynecology and Obstetrics, Jagiellonian University, Krakow, Poland.

Objectives: The first goal of this study was to analyze the diagnostic performance of the 4-chamber view, 3-vessel and trachea view, and their combination in color mapping during early cardiac evaluations for selecting cases suspicious of congenital heart defects. The second goal was to describe the most common abnormal flow patterns at the levels of the 4-chamber and 3-vessel and trachea views in the late first trimester.

Methods: We conducted a prospective observational study in which a simple cardiac sonographic protocol was applied in fetuses at gestational ages of 11 weeks to 13 weeks 6 days.

Results: A total of 1084 patients with known postnatal or autopsy findings were included in the study. The median maternal age was 32.3 years (range, 27-40 years). The median crown-rump length was 62.2 mm (range, 45-84 mm). Overall, there were 35 cases with a confirmed congenital heart defect (3.22%), including 16 accompanied by aneuploidy. We found that our simple first-trimester cardiac protocol was an effective screening method for congenital heart defects. The most effective approach of the 3 evaluated by us was the combined application of the 4-chamber and 3-vessel and trachea views in color mapping compared to the 4-chamber and 3-vessel and trachea views alone. We defined the most common ventricular inflow patterns and the V sign. The technique we used was simple and easy to reproduce.

Conclusions: We confirmed that evaluation by two basic cardiac views allows for selection of most cases with a univentricular heart, atrioventricular septal defects, coarctation of the aorta, pulmonary stenosis, pulmonary atresia, and conotruncal defects.
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April 2015

[The assessment of the dependence between antigen CA 125 and nicotinism in patients with benign ovarian tumors including endometrial cysts].

Przegl Lek 2014 ;71(6):319-22

Unlabelled: Cancer antigen CA-125 is a marker that is primarily used to differentiate benign from malignant tumors as well as to monitor response to ovarian cancer treatment. Taken as a separate marker, it displays low sensitivity and specificity in ovarian cancer diagnosis; however, in combination with other markers it may be successfully applied especially in postmenopausal women. Elevated CA-125 levels in blood serum indicate cancerous as well as non-cancerous diseases. Research aiming to determine environmental factors that may have influence on antigen CA-125 level, and thus on the assessment of this marker's application in gynecological and oncological diseases continues.

Objectives: the aim of the present research is an attempt to estimate the influence of nicotinism on antigen CA-125 in blood serum in patients with diagnosed benign ovarian tumors including endometrial cysts.

Material And Methods: 174 women aged 16-85 years with diagnosed benign ovarian tumor were qualified for the study. In all patients level of antigen CA-125 in blood serum was assessed preoperatively and nicotinism history was taken. Also transvaginal ultrasound was performed to obtain preliminary diagnosis. Smoking and non-smoking patients were classified into two groups, namely of those with histopathologically confirmed cysts of endometrial type and those with non-endometrial benign ovarian tumors.

Results: statistical analysis did not prove any dependence between the CS-125 antigen level and nicotinism in any of these groups. Also additional analysis with division into premenopausal and postmenopausal patients did not determine any statistically significant dependence.

Conclusion: Nicotinism does not significantly influence the CA-125 antigen level in patients with benign However, the connection between the addiction severity and its influence on antigen CA-125 in blood serum cannot be excluded. ovarian tumors or endometrial cysts.
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November 2014

First trimester tricuspid regurgitation and fetal abnormalities.

J Perinat Med 2015 Sep;43(5):597-603

Background: Tricuspid regurgitation (TR) is a common sonographic finding during the fetal life. It has been reported in 7% of normal fetuses. It may be associated with aneuploidy and with both cardiac and extracardiac defects.

Objectives: In this study, we have looked at the characteristics of fetuses with and without TR at 11+0 to 13+6 weeks' gestation. Groups were compared with respect to the following variables: prevalence of chromosomal defects; other markers of aneuploidy; fetal cardiac; and extracardiac anomalies.

Methods: The study group included women, who underwent an ultrasound examination at 11-13+6 weeks' gestation between 2009 and 2012. The inclusion criteria were singleton pregnancies with crown-rump length measurements of 45-84 mm where the pregnancy outcome was known.

Results: Some 1075 patients met our inclusion criteria including 979 fetuses without TR and 96 with TR. There were 72 cases of aneuploidy diagnosed (6.7%). Isolated TR was found in 53 euploid fetuses (5.2%). All of the TR(+) aneuploid fetuses (n=40) had additional ultrasound markers present. Extracardiac anatomy showed a higher prevalence of abnormalities in the group of TR positives (12.5%) vs. TR negatives (1.6%). Abnormal cardiac findings were more frequent in the TR-positive group independently of chromosomal status and were found in 18.8% of fetuses with TR and in 1.9% with a normal tricuspid flow.

Conclusions: TR in combination with other markers is the strongest predictor for aneuploidy. TR, as an isolated parameter, is a poor screening tool both for all and for each individual chromosomal abnormality and congenital cardiac defects.
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September 2015

Diagnostic accuracy of three-dimensional sonohysterography compared with office hysteroscopy and its interrater/intrarater agreement in uterine cavity assessment after hysteroscopic metroplasty.

Fertil Steril 2014 May 26;101(5):1392-9. Epub 2014 Feb 26.

Department of Gynecology and Oncology, Jagiellonian University, Krakow, Poland.

Objective: To compare the diagnostic accuracy of three-dimensional sonohysterography (3D-SIS) and office hysteroscopy in uterine cavity assessment after hysteroscopic metroplasty (HM) and determine the interrater/intrarater agreement for 3D-SIS.

Design: Prospective observational study.

Setting: University hospital, private hospital, and clinic.

Patient(s): One hundred forty-one women undergoing HM for septate uterus with a history of miscarriage and/or infertility.

Intervention(s): 3D-SIS and office hysteroscopy at 6-8 weeks after HM.

Main Outcome Measure(s): Shape of the uterine cavity, length of the fundal notch (≥1 or <1 cm), and the presence of intrauterine adhesions were assessed, and the interrater/intrarater agreement of 3D-SIS was evaluated in 30 randomly selected patients.

Result(s): Uterine abnormalities were detected with the use of hysteroscopy in 18 (12.8%) of 141 women. 3D-SIS was highly accurate (97.2%), sensitive (97%), and specific (100%), with a positive predictive value of 100% and a negative predictive value of 85%. The diagnostic values of hysteroscopy and 3D-SIS were not significantly different (McNemar test). 3D-SIS showed substantial interrater/intrarater agreement regarding overall uterine cavity evaluation (κ = 0.79 and 0.78, respectively).

Conclusion(s): 3D-SIS demonstrated substantial interrater/intrarater agreement for the postoperative evaluation of the uterine cavity, being as diagnostically accurate as hysteroscopy. The use of second-look hysteroscopy may be limited to cases that require reoperation.
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May 2014

[Evaluation of the recurrence and residual lesions incidence after loop electroexcisional procedure and cold knife conisation].

Przegl Lek 2012 ;69(9):658-62

Katedra Ginekologii i Połoinictwa UJ CM, Kraków.

The aim of this paper was the evaluation of the recurrence and residual lesions of cervical intraepithelial neoplaisa (CIN) incidence after LEEP (loop electro excisional procedure) and cold knife conisation. The clinical material was 210 women aged 22-65 years of life referred to the Department of Gynecology and Oncology Jagiellonian University Medical College in Krakow, Poland, the period in 2000- 2005 years, with initial cytological pap diagnosis-HSIL. (high grade squamous intraepithelial lesion-HSIL) according to The Bethesda System. The study group was 115 women with colposcopically visible lesions, which was qualified to the LEEP procedure. The controls were 95 women, preoperatively diagnosed based on colposcopically directed biopsy of the ectocervix and cervical canal curettage. In all cases the recurrence of cervical dysplasia and residual disease of cervical intraepithelial neoplasia incidence were analyzed. The follow-up period was 5 years with Pap smear and colposcopy every 3 months, for the first 2 years and every 6 months in subsequent 3 years. In case of recurrence which was diagnosed within first 6 months the residual disease was assumed rather than recurrence one. Data were statistically analyzed. We conclude that the therapeutical effect depends on CIN (cervical intraepithelial neoplasia) localization within cervix, because in case of cervical canal localization the recurrence and residual disease percentage is significantly higher in comparision to the ectocervix localization. This is why the colposcopic precise localization of the lesion within cervix is of the great importance. The free margins of the removed tissue speciemen are also the important prognostic factor. Most of the recurrence are diagnosed within the first year after initial procedure and does not depend on the margins involvement.
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March 2013

[Translabial ultrasonography in pelvic floor prolapse and urinary incontinence diagnostics].

Ginekol Pol 2012 Sep;83(9):694-9

Klinika Ginekologii i Onkologii UJ CM, Kraków, Polska.

Technological advances in the construction of sonographic devices and increasingly universal access to such tests considerably widens the range of diagnostic application of the sonographic examination. This situation also refers to pelvic organs prolapse. At present, sonographic sets used in everyday obstetrical-gynecological practice allow for insight into the structures forming the female pelvic floor, and the obtained images constitute a valuable addition to the physical examination. Positioning the sonographic transducer on a the perineum enables to visualize the three compartments of the female pelvis minor. After freezing the image, it is possible to assess the position of anatomical structures in relation to bones and designated surfaces, establish mutual distances and measure appropriate angles. Most information can be obtained in this manner within the range of the frontal compartment, whose damage is often linked with urinary incontinence. The examination standards developed so far, including the analysis of the quantitative parameters, greatly minimize the potential subjectivity of the assessment of the existing disorders. Apart from its low costs, the main value of the sonographic examination of the pelvic floor is the possibility to dynamically assess the changes in statics which take place during functional testing. Not only does it have a cognitive significance, but also it allows to adjust the scope of the surgical correction to the existing damages. Thus, indirectly it can contribute to the reduction of a number of subsequent remedial surgeries. Three-dimensional sonography allows to thoroughly examine the construction and functioning of the anal levators and to detect their possible damage. It is the trauma to these muscles--occurring, among others, during childbirth--that is one of the major causes of pelvic organs descent and prolapse in women. Sonographic examination also enables to visualize the artificial material, the use of which is increasingly frequent in the surgical treatment of pelvic organs prolapse. The remedial kits currently in use are not visible in classic X-ray examinations and CT however, they can be easily visualized by means of a sonographic test. This way it is possible to locate the positioned tapes or meshes and to establish their orientation towards the urethra, the bladder and the anus. It is also possible to observe the complications (e.g. hematomas) following the surgical procedures via the transvaginal access. Transperineal sonography is a relatively inexpensive method that may be performed in almost every ultrasonographic laboratory Its value, approaching the MRI diagnostic value in the assessment of the pelvic floor defects and its low cost, place ultrasonography on the first place among the methods of imaging the pelvic and uro-genital diaphragm. The results of diagnostics of pelvic organs prolapse obtained by placing the sonographic head on the patient's perineum may also help in establishing the changes of the support apparatus for the uterus and the vagina, bladder urethra and perineum during functional testing and, thus, to verify the clinically established degree of the prolapse. It seems, also, that this method may be used during peri-urethral injections of specific substances and post-application follow-up, an increasingly frequently employed method of urinary incontinence treatment.
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September 2012

Two- and three-dimensional ultrasonography and sonohysterography versus hysteroscopy with laparoscopy in the differential diagnosis of septate, bicornuate, and arcuate uteri.

J Minim Invasive Gynecol 2013 Jan-Feb;20(1):90-9

Department of Gynecology and Oncology, Jagiellonian University, Krakow, Poland.

Study Objective: To estimate the diagnostic accuracy and to compare the diagnostic value of 3-dimensional sonohysterography (3D-SIS), 3-dimensional transvaginal ultrasonography (3D-TVS), 2-dimensional sonohysterography (2D-SIS), and 2-dimensional transvaginal ultrasonography (2D-TVS) (initial and expert diagnosis) in the differential diagnosis of septate, bicornuate, and arcuate uteri.

Design: Prospective clinical study (Canadian Task Force II-2).

Setting: University hospital and private hospital and clinic.

Patients: A total of 117 women with a history of recurrent abortions or infertility and a 2D-TVS initial diagnosis of a septate, bicornuate, or arcuate uterus.

Interventions: Expert 2D-TVS, 3D-TVS, 2D-SIS, and 3D-SIS performed by experienced examiners and hysteroscopy with laparoscopy to establish the final diagnosis.

Measurements And Main Results: Hysteroscopy performed in conjunction with laparoscopy (HL) detected 23 arcuate, 60 septate, 22 bicornuate, and 12 normal uteri. 3D-SIS showed perfect diagnostic accuracy (100.0%) in general detection of uterine abnormalities, compared with initial 2D-TVS (77.8%), expert 2D-TVS (90.6%), 2D-SIS (94.0%), and 3D-TVS (97.4%). In the overall diagnosis of uterine anomalies, all of the diagnostic methods had statistically significantly better diagnostic value than initial 2D-TVS (p < .001), whereas 3D-SIS was the only method that was better than expert 2D-TVS (p < .001).

Conclusions: Although 3D-SIS was identical to HL, with the highest accuracy, there was no significant difference in diagnostic value between 3D-TVS with 2D-SIS and 3D-SIS or between expert 2D-TVS and 3D-TVS with 2D-SIS. The high diagnostic value of these ultrasonographic tools questions the need for endoscopy in the differential diagnosis of the most common congenital uterine anomalies.
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July 2013

DFF45 expression in human endometrium is associated with menstrual cycle phases and decreases after menopause.

Gynecol Obstet Invest 2012 1;73(3):177-82. Epub 2012 Mar 1.

Department of Gynecology and Oncology, Jagiellonian University, 23 Kopernika Street, Krakow, Poland.

Background: Human endometrium undergoes cyclic structural and functional modifications, and if no conception occurs menstruation is observed as the result of endometrial cell apoptosis via DFF40/DFF45 complex activation. In postmenopausal endometrium, the proliferative potential of endometrial cells is decreased, while their susceptibility to apoptosis increases.

Methods: The study group comprised 104 nonpregnant adult women (78 of reproductive age and 36 after menopause) with no neoplasm or hormonal treatment during the past 6 months. Immunohistochemistry and Western blot methods were used for DFF45 identification and semiquantitative assessment of its amount.

Results: Significantly more DFF45-positive cells were detected in the endometrial glands compared to stroma, and this pattern was constant throughout the whole menstrual cycle and also present in postmenopausal endometrial species. The lowest mean relative amount of DFF45 was detected in postmenopausal endometrial samples. In women of reproductive age, the highest mean relative amount of DFF45 was identified in an early secretory phase of the menstrual cycle, the lowest median value of the relative amount of DFF45 was observed in the late proliferative phase, and the difference was significant.

Conclusion: The DFF45 level in human endometrium corresponds to the respective phase of the menstrual cycle and decreases significantly after menopause.
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August 2012

[The value of three-dimensional multiplanar (MPV) and volume contrast imaging (VCI) in the ultrasound evaluation of endometrial pathology].

Przegl Lek 2012 ;69(12):1271-5

Klinika Ginekologii i Onkologii, Collegium Medicum, Uniwersytetu Jagiellońskiego w Krakowie.

The aging of the women population as well as widespread use of the ultrasound leads to an increased detection of abnormal endometrial characteristics. The aim of this study was to assess the value of three-dimensional ultrasound viewing options: multi-planar view (MPV) and volume contrast imaging (VCI) in the endometrial evaluation. 147 women, referred for endometrial sampling, because of bleeding or an abnormal endometrial two-dimensional ultrasound image were enrolled in the study. Before dilation and curettage, all patients underwent three-dimension ultrasound scans for endometrial thickness measurements and endometrial-myometrial junction assessment. Ultrasound results and the presence of abnormal vaginal bleeding were compared with pathological diagnosis. Sensitivity, specificity, negative predictive value, and positive predictive value for abnormal vaginal bleeding, irregular endometrial-myometrial junction and endometrial thickness were established. Logistic regression model was used to assessed the relationship between the characteristics and the incidence of endometrial pathology. For each of the independent variables odds ratios were calculated. Sensitivity, specificity of the endometrial thickness cut-off 11 mm were 73.8%, 74.4%, for 10.5 mm 76.2%, 69.8% respectively. The irregular endometrial-myometrial junction reached 70.5% sensitivity and 93% specificity. Odds ratios for 10,5 mm cu-off value of the endometrial thickening and irregular E-M junction were calculated: 4.10 [95% CI: 1.14-14.74] and 36.07 [95% CI: 7.10-183.27]. The negative predictive value of any of these parameters did not exceed 70%. The combination of 3D ultrasound parameters and the occurrence of abnormal vaginal bleeding has reached only 53% sensitivity. In the case of connection of two of these three indices, increased sensitivity of 76.9% and specificity of 82.4%. In an unselected group of women in terms of menopausal status and symptoms endometrial thickness measured and the evaluation of endometrial-myometrial junction using 3D ultrasound is less value in predicting the occurrence of endometrial cancer than in 2D and the endometrial volume calculation.
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August 2013

Diagnostic accuracy of sonohysterography, hysterosalpingography and diagnostic hysteroscopy in diagnosis of arcuate, septate and bicornuate uterus.

J Obstet Gynaecol Res 2011 Mar 11;37(3):178-86. Epub 2011 Feb 11.

Department of Gynecology and Oncology, Jagiellonian University, Krakow, Poland.

Aim: To evaluate the diagnostic accuracy of sonohysterography (SHG), hysterosalpingography (HSG) and diagnostic hysteroscopy (DH) in uterine anomaly detection and to assess the role of these various modalities in the differential diagnosis of arcuate, septate and bicornuate uteri.

Methods: Eighty-three women, with a history of recurrent spontaneous abortions or infertility and initial diagnosis of uterine anomaly were included in the study. Diagnostic work-up comprised of SHG, HSG and DH. To assess the accuracy of these methods all the patients underwent hysterolaparoscopy to establish the final diagnosis. The correlation between the results of each method was evaluated and diagnostic accuracy of each method was assessed in the whole group of women as well as in subgroups of arcuate, septate and bicornuate uteri using receiver operator curve (ROC) method by estimating the area under the curve (AUC).

Results: In the overall diagnosis of uterine anomalies, SHG with accuracy of 95.2% and correlation index of 0.873 (P < 0.001) proved to be a significantly better tool compared to DH (SHG(AUC) = 0.924 versus DH(AUC) = 0.761 P = 0.008), while no significant differences were observed between SHG versus HSG and DH versus HSG. SHG showed significantly higher accuracy (100.0%) compared to DH (80.7%) and HSG (80.7%) in differentiation of a septate (SHG(AUC) = 1.000 versus DH(AUC) = 0.816 P < 0.001 and SHG(AUC) = 1.000 versus HSG(ACC) = 0.818; P < 0.001) and bicornuate uterus (SGH(AUC) = 1.000 versus DH(ACC) = 0.707; P < 0.001 and SHG(ACC) = 1.000 versus HSG(AUC) = 0.790; P = 0.002).

Conclusion: SHG is a noninvasive, cost-effective method available in an outpatient setting that is highly accurate in identifying uterine anomalies, in particular septate and bicornuate uterus.
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March 2011

The frequency of CD25+CD4+ and FOXP3+ regulatory T cells in ectopic endometrium and ectopic decidua.

Reprod Biol Endocrinol 2010 Oct 5;8:116. Epub 2010 Oct 5.

Department of Gynecology and Oncology of the Jagiellonian University, Krakow, Poland.

Background: The presence of regulatory T (Treg) cells in human endometrium is crucial for maintaining immunological homeostasis within the uterus. For this study we decided to evaluate the subpopulations of Treg cells in conditions where a disturbance in the immunological equilibrium in ectopic endometrium and decidua has been observed, such as in cases of ovarian endometriosis (involving local immune cell suppression) and ectopic pregnancy (involving an increase in local immune system activity). We then compared these findings to what we observed in the normal eutopic endometrium of women during the secretory phase of the menstrual cycle (with immune cells under individual control).

Methods: The endometrium tissue samples evaluated in our study were obtained from 47 women during one of two kinds of laparoscopic procedures. 16 of the women underwent laparoscopies due to Fallopian tube pregnancies (EP), and 16 due to ovarian endometrioma, while 15 women made up a control group. The presence of regulatory T cells in these tissue samples was evaluated by FACS.

Results: In our study, the percentages of FOXP3+ cells within the subpopulation of CD4+ T lymphocytes found in the decidua of the patients treated for Fallopian tube pregnancies were statistically significantly lower than both those observed in the ovarian endometriosis tissue samples and those found in the secretory eutopic endometrium samples of the control group.

Conclusion: The disturbance in the immunological equilibrium observed in ectopic endometrium and decidua would seem to be related to the alteration in the Treg cell population that occurs in these ectopic tissues.
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October 2010

[Ectopic pregnancy rupture--can it be prevented?].

Ginekol Pol 2009 Oct;80(10):734-9

Klinika Ginekologii i Onkologii Uniwersytetu Jagiellońskiego w Krakowie.

Objectives: To determine risk factors for ectopic pregnancy (EP) rupture based on the patients history and preoperative tests.

Materials And Methods: The retrospective study consisted of 175 women operated on due to EP in the Department of Gynecology and Oncology of the Jagiellonian University between 2000-2008. Tubal rupture was diagnosed at the time of surgery. The patients were then divided into three groups: those who had unruptured EP without bleeding, those who had unruptured EP with hemorrhage into peritoneal cavity and those who suffered ruptured tubal pregnancy Analysis was performed based on the following parameters: patient history preoperative laboratory tests (Hb, Hct, betaHCG), and ultrasound exam.

Results: Of the 175 cases of ectopic pregnancy included in the study 20% were unruptured without bleeding (A) and 40.6% unruptured with hemorrhage (B) while 39.4% were ruptured (C). There was a positive correlation between the diameter of the tubal lesion measured ultrasonographically and rupture (37.4 +/- 16 for C vs 29.7 +/- 12.9 for A; p=0.04). The gestational age of the groups differed significantly (p=0,001): C (56 +/- 1), A (49 +/- 3), and B (42 +/- 2). There was also a positive correlation between rupture and gravidity (1 +/- 1 for A vs 2 +/- 2 for C; p=0.02). Moreover a positive correlation of borderline significance was discerned between rupture and parity (p=0.06). Additionally the preoperative hemoglobin and hematocrit values were significantly lower in the rupture group (p=0.001). There was no significant difference among the three groups in age, number of abortions, serum betaHCG, endometrial thickness, length of hospital stay or the time elapsed since the most recent pregnancy.

Conclusions: Low hemoglobin and hematocrit values, together with higher gravidity at the time of admission, may indicate an increased risk of tubal rupture.
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October 2009

Soluble HLA-G changes in maternal blood serum during the progression of labor.

Neuro Endocrinol Lett 2009 Mar;30(1):67-73

Department of Gynecology and Oncology, Jagiellonian University, 23 Kopernika Str, 31- 501 Krakow, Poland.

Background: The expression of the HLA-G antigen from implantation toward term is crucial for the growth of a semiallogenic fetus as it shields this fetus from the maternal cytotoxic response. Little is known, however, about the potential role of soluble HLA-G isoforms during delivery. The initiation of labor is associated with a complex molecular response leading to a brief activation of the maternal immune system with an accompanying capacity to restrict this activation, and HLA-G seems to be an important factor in enabling the proper immune response at the maternal fetal interface.

Methods: In our study the levels of soluble HLA-G concentration were evaluated in the blood serum samples obtained from 47 pregnant women who either underwent cesarean sections or delivered vaginally. The patients were divided into three subgroups according to the progression of labor at the time of the cesarean or, in cases of vaginal delivery, according to the duration of the pregnancy.

Results: We have observed that the progression of labor is associated with a continuous increase in the sHLA-G plasma level. The sHLA-G levels were statistically significantly higher in the blood sera obtained from the women in advanced labor than from the women who were at the beginning of labor.

Conclusion: The changes in sHLA-G concentration levels observed during the stages of labor may indicate that this isoform participates in maintaining reproductive tract homeostasis.
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March 2009

The increase in metallothionein and ectopic decidual immunoreactivity with respect to the progression of labor at term and the lack of analogical changes in placental abruption.

Am J Reprod Immunol 2008 Sep;60(3):204-13

Department of Pathomorphology of the Jagiellonian University, Krakow, Poland.

Problem: The coexistence of immune and decidual cells is related to the development of a resistance to immune-mediated apoptosis in both ectopic and eutopic decidua. This unique feature of endometrial cells seems to be linked with the expression of metallothionein (MT), an inhibitor of apoptosis.

Method Of Study: The MT immunoreactivity level was assessed in 82 eutopic (CC) and ectopic (cesarean scar deciduosis - CSD) decidual tissue samples obtained from patients during cesarean sections at term and from patients on whom cesarean sections were performed on account of placental abruption (PA).

Result: Statistically, significantly higher levels of MT immunoreactivity were found in eutopic and ectopic decidua sampled during cesarean sections performed on patients with advanced labor when compared to the levels found in tissues sampled during cesarean sections on patients without labor. No differences were observed in the MT immunoreactivity levels in decidual tissue samples derived from patients who had undergone cesarean sections on account of PA with respect to the progression of labor at the time of the surgical procedure. Statistically, the decidual MT immunoreactivity levels were significantly higher in the PA than the CC subgroups and in the PA than the CSD subgroups correlating with the stage of labor.

Conclusion: MT in decidual cells seems to be responsible for the proper coexistence between decidual cells and activated immune cells that infiltrate both eutopic and ectopic decidua during cesarean section and PA.
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September 2008

[Protective and therapeutic effect of leptin in acute pancreatitis evoked by ischemia/reperfusion].

Folia Med Cracov 2003 ;44(1-2):93-108

Katedra Fizjologii Wydziału Lekarskiego Collegium Medicum Uniwersytetu Jagiellońskiego ul. Grzegórzecka 16, 31-531 Kraków.

Leptin is a hormone implicated in the regulation of the food intake and body weight, but also increasing number of evidence suggest that leptin participates in the regulation of inflammatory processes. The aim of our study was to examine the influence of exogenous leptin administration on the development and the course of acute ischemic pancreatitis. Acute pancreatitis was induced by temporary limitation of pancreatic blood flow, followed by reperfusion. Leptin was administered three times daily at the dose 10 or 50 micrograms/kg. Studies were terminated at 1, 3, 5, 10 and 21 days after induction of acute pancreatitis. Leptin administration reduced development of pancreatic damage and accelerated pancreatic regeneration. It was manifested by the decrease in serum lipase and amylase activity, the reduction in serum interleukin-1 beta concentration and the improvement of pancreatic histology. Additionally, treatment with leptin caused the increase in the pancreatic blood flow and pancreatic DNA synthesis. Serum interleukin-10 concentration was not effected by leptin administration. Leptin at the dose 50 micrograms/kg was more effective than 10 micrograms/kg. We conclude that leptin is able to limit the pancreatic damage in the course of ischemic pancreatitis and accelerates the pancreatic tissue repair. These effects of leptin seem to be dependent on the increase in pancreatic cell growth, the limitation of pro-inflammatory interleukin-1 beta release and the improvement of pancreatic blood flow.
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August 2004

Stimulation of sensory nerves and CGRP attenuate pancreatic damage in ischemia/reperfusion induced pancreatitis.

Med Sci Monit 2003 Dec;9(12):BR418-25

Department of Physiology, Jagiellonian University Medical School, Cracow, Poland.

Background: Previous studies have shown that sensory nerves and calcitonin gene-related peptide (CGRP) affect caerulein-induced pancreatitis. The aim of this study was to examine the role of capsaicin-sensitive nerves and the impact of CGRP administration on necrotizing pancreatitis induced by ischemia/reperfusion.

Material/methods: Ablation of sensory nerves was made by capsaicin 10 days before induction of pancreatitis. Acute pancreatitis was induced in rats by limitation of pancreatic blood flow (PBF) followed by reperfusion. Treatment with saline or CGRP (10 g/kg s.c.) or stimulation of sensory nerves by low doses of capsaicin (0.5 mg/kg s.c.) was performed 1 h before ischemia. After 1 h reperfusion we examined pancreatic blood flow (PBF), plasma amylase and lipase activity, plasma interleukin-1beta (IL-1beta) concentration, pancreatic DNA synthesis and morphological signs of pancreatitis.

Results: Ischemia followed by 1 h reperfusion led to induction of necrotizing pancreatitis, manifested by morphological signs of pancreatic damage, decrease in pancreatic DNA synthesis and PBF, as well as an increase in plasma amylase and lipase activity and plasma IL-1beta concentration. Both, treatment with CGRP and stimulation of sensory nerves attenuated pancreatic damage. Ablation of sensory nerves enhanced I/R evoked pancreatic damage. The deleterious effect of deactivation of sensory nerves on I/R-induced pancreatitis was partly reversed by administration of CGRP prior to I/R.

Conclusions: Stimulation of sensory nerves protects the pancreas against damage evoked by I/R, whereas ablation of these nerves aggravates tissue damage in the pancreas exposed to I/R. The beneficial effect of sensory nerves is partly dependent on CGRP release.
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December 2003