[Use of methotrexate in the ectopic pregnancy and pregnancy of unknown location]. / Pouzití metotrexátu u ektopické gravidity a tehotenství neznámé lokalizace.

OBJECTIVE: There are only a few gynaecological departments in the Czech Republic that use medical treatment of the ectopic pregnancy (EP) or persistent pregnancy of unknown location (PUL). We have started using this method in 2008 at our clinic. The aim of this study was to assess the success rate of conservative medical treatment with methotrexate (MTX) in the dose of 1 mg/kg intramuscularly in patients with ectopic pregnancy or persistent pregnancy of unknown location and to compare the results of clinical history, clinical finding and laboratory results in a group of successful and a group of unsuccessful treatment. TYPE OF STUDY: Retrospective analysis. SETTING: Charles University in Prague, 1st Medical Faculty and Hospital Bulovka, Department of Obstetrics and Gynaecology, Prague. METHODS: Patients diagnosed with EP or persistent PUL diagnosed at the outpatient of our clinic in 01/2008 - 08/2014 who were hemodynamically stable and fulfilled the indication for medical treatment were enrolled in the study. Treatment success was decrease of free subunit of ß-hCG (ß-hCG) < 5 IU/L independent of the number of methotrexate doses administered. RESULTS: Two hundred and eleven patients were diagnosed with EP or PUL, sixty-three were eligible for our study and fulfilled the criteria for methotrexate treatment, fifty six women were finally analysed. From this number forty eight (86%) had clinically and laboratory diagnosed EP and eight (14%) were diagnosed with persistent PUL. Forty one patients (73%) had a successfull treatment (Group I) with the ß-hCG level decrease <5 IU/L in a mean time of 27 days. When comparing the data of successful and unsuccessful treatment (Group II) we found a difference in the non-significant initial ß-hCG level. In Group I there was a median ß-hCG 538 IU/L (100-3852 IU/l), whereas in the unsuccessful Group II it was 1100 IU/L (300-3240 IU/l). Group I included more nuliparous women and more women with clinical histories of EP. Group II included more heavy smokers. The mean hematosalpinx diameter for group II, measured by transvaginal ultrasound, was larger. There were also more patients with endometriosis or deep infiltrating endometriosis in Group II, subsequently verified during laparoscopy, compared to Group I. There was no tubal rupture in these patients. CONCLUSION: The results of our study are comparable with foreign literature publications. We consider the pharmacological treatment of ectopic preganancy or persistent pregnancy of unknown location as effective and relatively safe for patients, with similar impact on a woman's fertility as laparoscopic salpingectomy.

Changes in placental angiogenesis and their correlation with foetal intrauterine restriction.

TYPE OF STUDY: Summary review. SETTING: Department of Gynaecology and Obstetrics, 1st Faculty of Medicine, Charles University and Hospital Na Bulovce, Prague; Department of Physiology, Faculty of Science, Charles University, Prague; Department of Children and Adolescent Medicine, 1st Faculty of Medicine, Charles University in Prague and General Teaching Hospital, Prague. INTRODUCTION: Intrauterine growth restriction (IUGR) is one of the most common problems in obstetrics. Its incidence is ranging between 3-10%, according to the type of study population and chosen criteria. The cutoff value mainly used for defining the IUGR is weight below the 10th percentile for gestational age. The minority of authors defines the cutoff value under the 5th or 3rd percentile. Any pathological interference with normal vascular development of placenta may have a critical impact on foetal growth and development. Ischaemia is the most common cause of IUGR in normally well-supplied placenta. IUGR is then a consequence of insufficient extension, branching, and dilatation of capillary loops during the formation of terminal villi. METHODS: This paper is a review focused on up-to-date-known data concerning changes in placental angiogenesis and their impact on IUGR development. CONCLUSION: The aim of this review is to summarize the knowledge concerning the mechanisms of development of the vascular supply to the placenta under physiological conditions and in conditions that result in IUGR.

[The 2-dose schedule of HPV vaccines in young adolescents]. / Dvoudávkové ockovací schéma HPV vakcín u mladých adolescentu

OBJECTIVE: To summarize new knowledge about the 2-dose HPV vaccine schedule in young adolescents. DESIGN: Review article. SETTING: Department of Gynaecology and Obstetrics, First Faculty of Medicine, Charles University and Hospital Na Bulovce in Prague; Oncogynaecological Center, First Faculty of Medicine, Charles University and General University Hospital in Prague. RESULTS: The goal of immunization programs in many countries is the prevention of cervical cancer using either the bivalent or the quadrivalent HPV vaccine. The vaccines, which were designed to prevent cervical cancer outcomes in adults, need to be administered before the onset of sexual activity. Since the HPV vaccines are among the most expensive of all the widely recommended vaccines, limited financial resources restrain the HPV vaccination in some countries around the word. Higher immunogenicity of both HPV vaccines in young adolescents, as well as potential cost savings, have prompted discussions about the efficacy of the 2-dose HPV vaccine schedule. Results of the immunobridging studies showed that two doses of the bivalent and the quadrivalent HPV vaccine in young girls induced geometric mean antibody titers that were non-inferior to geometric mean antibody titers elicited in older girls and women with three doses of the same vaccine. Non-inferiority for HPV-16, -18, -31 and -45 was obtained for the 2-dose of the bivalent HPV vaccine in girls 9-14 years old in the period of 48 months and for HPV-6, -11, -16 and -18 for the 2-dose of the quadrivalent HPV vaccine in girls 9-13 years old in the period of 36 months. CONCLUSION: These results indicate that the bivalent and the quadrivalent vaccine HPV vaccine applied in 2 doses has sufficient immunogenity in young girls.

Tailoring surgical treatment of cervical precancerosis.

OBJECTIVE: To summarize new data which can help in decision on tailoring treatment of cervical precancerosis. DESIGN: Review article. SETTING: Department of Gynaecology and Obstetrics, First Faculty of Medicine, Charles University and Hospital Na Bulovce in Prague; Oncogynaecological Center, First Faculty of Medicine, Charles University and General University Hospital in Prague. RESULTS: Precancerous lesions of the cervix are represented by squamous cervical intraepithelial neoplasias (CIN) and glandular adenocarcinomas in situ (AIS). The usual treatment of cervical precancerosis is conisation. However, some complications, particularly subsequent adverse pregnancy outcomes, follow all surgical treat-ments of cervix. The treatment could be postponed in women who wish to conceive and who suffer from CIN with a low risk of transformation to invasive cancer. The presence of modifying factors can help to stratify CIN lesions according to their malignant potential. The determination of detected HPV genotypes may help in this decision, because the fate of CIN 2/3 depends on the genotype of associated HPV infection. Cervical lesions associated with HPV 16, 18 or 45 are at a much higher risk of rapid progression to invasive cancers than lesions associated with other HR HPV genotypes. Surgical treatment of CIN 2/3 in women with a desire for future child-bearing can be postponed in cases non-associated with HPV 16, 18 and 45, on a case by case basis. Attempts are made to improve evaluation of the lesions by using biological and molecular markers, especially p16INK4a staining. Younger age, ongoing pregnancy, favourable colposcopic findings, negative p16INK4a staining and immunocompetency are independent factors supporting the choice of conservative management. Adenocarcinoma in situ management substantially differs from the management of CIN. CONCLUSION: It is important both to assess all modifying factors correctly and to minimize any harm from unnecessary surgical treatment or overtreatment of cervical precancer lesions. KEYWORDS: cervical intraepithelial neoplasia, adenocarcinoma in situ, conisation, tailoring treatment, human papillomavirus genotype, p16.

[Anticipated efficacy of HPV vaccination in prophylaxis against nongenital cancers]. / Predpokládaná úcinnost HPV vakcinace v profylaxi nongenitálních karcinomu

BACKGROUND: There is a considerable number of studies on the efficacy HPV (human papillomavirus) vaccination against different cancers but relevant information is scattered in diverse journals. This paper is a review summarizing current knowledge of the potential of HPV vaccination against all HPV related cancers. AIM: HPV infection is probably the most frequent sexually transmitted disease. At least 13 HPV genotypes are classified as carcinogenic or probably carcinogenic in respect to cervical cancer. Almost 100% of cervical cancers are linked to HPV infection. HPV 16 and HPV 18 are the most frequently involved genotypes and account together for approximately 70% of cervical cancer in the world. Persistent high risk HPV infection is responsible for a significant proportion of vulvar, vaginal, anal and penile carcinomas. The virus has also been implicated in oncogenesis of head and neck cancers, including oropharyngeal cancers. HPV infection can play an important role in cancerogenesis of lung, esophagus, breast, and colon and rectum. On the contrary, published results indicate that HPV infection is not associated with prostate oncogenesis. Strong predominance of HPV 16 has been reported for all HPV associated cancer sites. Generally, it is estimated that approximately 5.2% of all cancers are associated with oncogenic HPV infection. Currently, there are two vaccines on the market; quadrivalent Silgard® (Gardasil®) and bivalent CervarixTM. Large trials for both vaccines have shown efficacy against HPV related infection and disease. Efficacy has been very high in HPV naive subjects to vaccine related types. While HPV vaccination is currently approved for the prevention of cervical cancer, it also has the potential in the prevention of all HPV associated malignancies. The Czech republic belongs to countries that cover HPV vaccination of girls at the age of 13- 14 years by general health insurance. Overall impact of this vaccination remains to be evaluated. The new issues of the role of HPV in oncogenesis, as well as the potential effect of HPV vaccination against HPV related nongenital cancers are discussed. CONCLUSION: Approximately 5.2% of all human cancers are associated with oncogenic human papillomavirus infection. HPV vaccination against the most risky HPV oncotypes may cause a significant reduction of these cancers mainly in the HPV naive population.

Bad and Bid - potential background players in preneoplastic to neoplastic shift in human endometrium.

The most common malignancies of the female genital tract are endometrial carcinomas, whose are generally proceeded by hyperplasia. The maintenance of tissue homeostasis is to great extent governed by apoptosis, whose defects can lead to the preneoplastic and/or cancerous changes. Endometrial apoptosis involves among others three groups of proteins of the Bcl-2 family. First group contains anti-apoptotic proteins (e. g. Bcl-2, Bcl-xL). The other two groups belong to the pro-apoptotic proteins with three (e. g. Bax, Bak) or one (e. g. Bad, Bid) so-called BH domains. Bad and Bid trigger the oligomerization of Bak and Bax protein, which permeabilize the outer mitochondrial wall. Unlike Bid, Bad cannot directly trigger apoptosis. Instead, Bad lowers the threshold at which apoptosis is induced, by binding anti-apoptotic Bcl-2 proteins. However, their mutual counterbalance or synergism in the human endometrium has not been reported yet.In this study, the levels of Bid and Bad were measured using SDS-PAGE and Western blotting with specific antibodies, with the aim to analyse expression of Bid and Bad proteins in normal (NE), hyperplastic (HE) and cancerous (CE) endometrium. We demonstrated that Bid expression in CE reached only 47% and 50% of this observed in NE and HE. Conversely, Bad expression in HE reached only 40% and 36% of this observed in NE and CE, respectively. We detected no significant changes of Bid expression between HE and NE, and levels of Bad protein were not different between CE and NE.Trend of Bid and Bad protein expression is clearly opposite in HE and CE. We hypothesise that disrupted apoptotic program in CE seems to be reduced further by lowering levels of direct apoptotic trigger protein Bid. We suggest that the adenocarcinoma tissue of human endometrium thus tries to strengthen its apoptotic effort by lowering the apoptotic threshold via higher Bad levels.

[The reasons of changes in revised staging for carcinoma of the vulva]. / Duvody zmen ve stagingu karcinomu vulvy.

BACKGROUND: Review of revised staging system for vulva, explaining the changes of staging and their impact on the prognosis of disease is presented. AIM: The main objectives of a reliable staging system include an assessment of prognosis, planning treatment, and the evaluation of their outcomes. A good staging system must meet three basic characteristics: validity, reliability and practicality. Since medical research and practice in the field of oncology have shown explosive growth, the staging of vulvar cancer and some other cancers did not give a good spread of prognostic groupings. Changes based on new findings were proposed in 2008 by the FIGO Committee on Gynecologic Oncology, approved, and published a year later the changes in the staging system for carcinoma of the vulva. Stage 0 was deleted, since it represents preinvasive lesion. Stage IA remained unchanged and stage I and II were combined. The number and morphology of the involved nodes were taken into account, and the bilaterality of positive nodes has been discounted. CONCLUSION: The purpose of a good staging system is to offer a classification of the extent of gynecological cancer, in order to provide a method of conveying ones clinical experience to others for the comparison of different treatment methods. As a result of the explosion of medical research in the field of oncology, the staging of some of the gynecological cancers became outdated and did not give a good spread of prognostic groupings. According to the revised staging for carcimona of the vulva, patients are divided to groups with similar prognosis. Therefore, exchange of relevant information between oncological centers is facilitated, thus disseminating knowledge and stimulating research in other parts of the world.

[Selective progesterone receptor modulators and their therapeutical use]. / Selektivní modulátory progesteronového receptoru a jejich terapeutické vyuzití

Currently developed selective progesterone receptor modulators (SPRMs) are steroid derived compounds with a bulky radical substitution at carbon 11. They interact with progesterone receptor and exert antagonistic or/and agonistic effects. Mifepristone was approved for pregnancy termination and ulipristal acetate as emergency contraception and pharmacological therapy of uterine fibroids. SPRMs inhibit endometrial proliferation and myoma growth, this suggests a therapeutical effect in cases of endometriosis and other estrogen-dependent diseases.

[Blockade of calcium channels - a perspectiveof male contraception?]. / Blokáda vápníkových kanálu - perspektiva muzské antikoncepce?

Besides condoms and vasectomy with their own limitations, no other reliable methods of contraception are available to men. Ion channels play a key role in maturation, capacitation and acrosome reaction of sperms. Blockade of calcium channels with pharmacological inhibitors or compounds isolated from plant extracts might be suggested as one of promising mechanisms of future male contraceptives.

[Prevalence of anal human papillomavirus infection among women and its relation to cervical HPV infection]. / Prevalence anální HPV infekce u zen a její vztah k cervikální HPV infekci.

OBJECTIVE: To summarize current knowledge of prevalence, duration and clearance of anal HPV infection among women and its relation to cervical HPV infection. DESIGN: Review article. SETTING: Department of Gynecology and Obstetrics, Hospital Na Bulovce and 1st Medical School of Charles University, Prague; Institute for the Care of Mother and Child, Prague; Gynecologic Oncology Center, Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical School of Charles University, Prague. RESULTS: The infection of human papillomavirus (HPV) is strongly associated with the development of anal cancer. Anal HPV infection is common and most anal HPV infections are transient. Women with cervical HPV infection, cervical dysplasia and cervical cancer are at the increased risk. Concurrent anal and cervical HPV infection is most prevalent among the youngest women. By contrast, the prevalence of anal infection alone remains relatively steady in all age groups. Compared with cervical infections, the overall distribution of HPV genotypes in the anus are more heterogeneous and include a greater proportion of nononcogenic types. A high degree of genotype-specific concordance is observed among concurrent anal and cervical infections, indicating a common source of infection. Tobacco smoking delays clearance of anal HPV. CONCLUSION: The high degree of genotype-specific concordance suggests that the cervix may be primary source and may serve as reservoir of HPV infection, too. Any type of sexual contact may be a route of transmission, history of anal intercourse is not a condition. The women with HPV related disease of low genital tract form high-risk group for acquisition of anal HPV infection and development of anal carcinoma.

[Current classification of malignant tumours in gynecological oncology--part II]. / Soucasná klasifikace zhoubných nádoru v onkogynekologii--cást II.

OBJECTIVE: Review of new staging systems for gynaecological cancers and their impact on prognosis and planning treatment. DESIGN: Review article. SETTING: Department of Gynaecology and Obstetrics, First Faculty of Medicine and University Hospital Na Bulovce, Charles University, Prague; Department of Radiotherapeutic Oncology, First Faculty of Medicine and University Hospital Na Bulovce, Charles University, Prague; Department of Pathology, University Hospital Na Bulovce, Prague. RESULTS: Every staging system should have 3 basic characteristics: it must be valid, reliable, and practical. Over the years, these staging classifications--with the exception of cervical cancer and gestational trophoblastic neoplasia--have shifted from a clinical to a surgical-pathological basis. Changes based on new findings were proposed in 2008 by the FIGO Committee on Gynecologic Oncology, approved in September 2008 by the FIGO Executive Board, and published in 2009. The greatest changes were made in the new staging system for carcinoma of the vulva and others in the new staging systems for carcinoma of the cervix and carcinoma of the endometrium. A new stanging system was also created for uterina sarcomas, based on the criteria used in other soft tissue sarcomas. A clinical staging system for carcinoma of cervix continues because surgical staging cannot be employed worldwide (especially in third world countries). Stage 0 has been deleted from the staging of all tumours, since it is pre-invasive lesion and it is not an invasive tumour. In the revised staging system for carcinoma of the endometrium, four fundamental changes have occurred, which will be discussed. Carcinosarcoma is still staged identically to carcinoma of the endometrium. A completely new staging system was created for adenosarcomas, along with an almost identical staging system for leiomyosarcoma and endometrial stromal sarcoma. The staging system for carcinoma of ovary and Fallopian tube remains without changes. CONCLUSION: Since medical research and practice in the field of oncology have shown explosive growth, the staging of some of the gynaecological cancers did not give a good spread of prognostic groupings. Therefore, revised FIGO and TNM staging system has been structured to represent major prognostic factors in predicting patients' outcomes and lending order to the complex dynamic behavior of gynaecological cancers. The purpose of good staging system is to offer a classification of the extent of gynaecological cancer in order to provide a method of conveying one's clinical experience to others for the comparison of treatment methods.

[Current classification of malignant tumours in gynecological oncology--part I]. / Soucasná klasifikace zhoubných nádoru v onkogynekologii--cást I.

OBJECTIVE: Review of new staging systems for gynaecological cancers and their impact on prognosis and planning treatment. DESIGN: Review article. SETTING: Department of Gynaecology and Obstetrics, First Faculty of Medicine and University Hospital Na Bulovce, Charles University, Prague. Department of Radiotherapeutic Oncology, First Faculty of Medicine and University Hospital Na Bulovce, Charles University, Prague. Department of Pathology, University Hospital Na Bulovce, Prague. RESULTS: The main objectives of any good staging system--essential to an evidence-based approach to cancer--include planning treatment, providing an assessement of prognosis and the evaluation of the results of treatment. With this approach, the exchange of relevant information between oncological centers is facilitated, thus disseminating knowledge and stimulating research in other parts of the world. A good staging system must have three basic characteristics: validity, reliability, and practicality. The first staging system for gynaecological cancers appeared around the turn of the 20th century and was applied to carcinoma of the cervix uteri. Classifications for the other gynaecological malignancies were not created until the 1950s. Over the years, these staging classifications--with the exception of cervical cancer and gestational trophoblastic neoplasia--have shifted from a clinical to a surgical-pathological basis. Some changes, brought about through new findings, were approved by the FIGO in 2008 and published in 2009. The greatest changes were made in the new staging system for carcinoma of the vulva, while others were made in the new staging systems for carcinoma of the cervix and carcinoma of the endometrium. A new stanging system was also created for uterine sarcomas, based on the criteria used in other soft tissue sarcomas. CONCLUSION: As a result of the explosion of medical research in the field of oncology, the staging of some of the gynaecological cancers became outdated and did not give a good spread of prognostic groupings. Therefore, revised FIGO and TNM staging system has been structured to represent major prognostic factors in predicting patients' outcomes and lending order to the complex dynamic behavior of gynaecological cancers. The purpose of a good staging system is to offer a classification of the extent of gynaecological cancer, in order to provide a method of conveying one's clinical experience to others for the comparison of different treatment methods.

Changes in expression of some apoptotic markers in different types of human endometrium.

The maintenance of tissue homeostasis and highly balanced counteraction of cellular proliferation and apoptosis are essential for tissue integrity. In our study, we evaluated the expression of apoptosis- regulating proteins Bcl-2, Bax and PARP, and executive apoptotic enzyme caspase-3 in normal, atrophic, hyperplastic and cancerous endometrium. Endometrial samples were obtained from patients who underwent curettage, hysteroresection or hysterectomy. The protein levels were quantified by immunoblotting. We observed a higher level of important apoptotic enzyme pro-caspase-3 and its active form in hyperplastic and cancerous endometrium, when compared to normal endometrium. The value of Bcl-2/Bax ratio, which reflects cellular resistance to apoptosis, was determined as > 1 for cancerous, normal, and atrophic endometrium. Thus, the effort to eliminate pre-neoplastic and neoplastic cells by apoptosis indicated by high pro-caspase-3 and caspase-3 levels seems to be overcome by a greater proliferative adjustment suggested by higher Bcl-2/Bax ratios in the samples examined. The PARP levels did not vary significantly among the groups. The levels of all examined proteins were significantly lower in atrophic endometrium. Our results suggest that pre-neoplastic and neoplastic states of human endometrium are not influenced simply by changes in apoptosis, but may also be affected by cellular proliferation. A high Bcl-2/Bax ratio as observed in cancerous endometrium can point to deregulation of apoptotic programmes. Thus, the onset and progression of endometrial malignancy could be linked to increased cellular proliferation with defects in apoptotic control.

[Significance of hysteroscopic resection in diagnostics of endometrial cancer]. / Význam resektoskopie v diagnostice karcinomu endometria.

OBJECTIVES: Endometrial cancer is the second most common malignancy of the female genital tract. Its incidence in the Czech Republic is 32/100 000 women and year with a permanent increasing tendency. In comparison with incidence, its mortality remains relatively low, with mortality ratio of 6.7 per 100,000 women and year. The decrease in mortality might be explained predominantly by early diagnostics. The most controversial issue is the potential risk of microscopic extrauterine dissemination of cancerous cells within the peritoneal cavity and circulation during hysteroscopy, and the question if the relatively high pressure of distension medium used during hysteroscopies may or may not multiply the risk. DESIGN: Retrospective study. MATERIALS AND METHODS: Totally, 400 endometrial biopsies were collected during years 2007-2009 at our clinic. In 56 patients, endometrial cancer was diagnosed. Afterwards, 44 women underwent surgery, during which peritoneal washing (lavage) and cytological examination were done. RESULTS: Fifty-six patients with histologically verified endometrial carcinoma were studied. The samples examined in the study were classified by grading as follows: G1 n=34, G1-2 n=10, G2 n=10, G3-4 n=2. In 44 cases that underwent radical surgery, no cancerous cells in peritoneal washings were found. Only in 1 case, the cytology obtained from peritoneal washing was considered to be suspicious. In 9 cases, carcinoma on the base of the polyp was detected, and in 2 cases, no residuum of cancer was observed after hysterectomy. CONCLUSION: In accordance with contemporary literature and based on our study, we suggest that hystero-resectoscopy does not increase the risk of dissemination of malignant cells within the peritoneal cavity and does not worsen the prognosis of the disease. On the contrary, the samples taken under visual control provide more precise and earlier diagnostics of endometrial cancer.

[Abortion induction in IInd trimester]. / Indukce potratu ve II. trimestru na Gynekologicko porodnické klinice FN na Bulovce.

STUDY AIM: Analysis of the set of women that underwent the termination of pregnancy in IInd trimester at the OBGYN clinic, Teaching Hospital Na Bulovce at interval of years 2006-2007. We appreciated the effect of method and compared with references in the literature. TYPE STUDY: Retrospective descriptive study. SEATTING: OBGYN clinic of the 1st faculty of Charles University, teaching hospital Na Bulovce, Prague. METHOD: Retrospective analysis of the set of women that underwent termination of pregnancy in the IInd trimester. Data are obtained from medical documentation and statistically processed. The analysis treats with 50 cases, in all of them, cervix was prepared with hydrophile dilators. In 37 cases were subsequently handed up prostaglandins intraamnially, in two cases generally intravenously, in two cases vaginally and 9 pregnancies were finished directly by dilatation and curettage without endeavour about expulsion. RESULTS: From 37 women after intraamnial administration of prostaglandins, 35 (94.6%) aborted successfully. Average time from amniocentesis to expulsion was 13 hours 45 minutes, 23 women aborted to 24 hours (62.2%). Undesirable effects were present in 12 cases (32.4%). CONCLUSION: Our record of local intraamnial administration of prostaglandins appears to be effective method. On the other hand, other methods are described in recent literature, which appear to be more efficient and have smaller occurrence of adverse effects.

Expression of phospho-Elk-1 in rat gut after the whole body gamma irradiation.

Gastrointestinal form is the second stage of acute radiation syndrome (ARS) with a threshold dose of 8 Gy in man. It represents an absolutely lethal clinical-pathological unit, necro-hemorrhagic enteritis and proctocolitis, with unknown causal therapy. Elk-1 is a protein acting as a transcription factor activating specified genes. The purpose of our study was to examine the expression of phospho-Elk-1 in irradiated jejunum and transversal colon of rats with radiation-induced enterocolitis and to assess the importance of this transcriptional factor as a biodosimetric marker of radiation-induced enteropathy. The laboratory rats were randomly divided into 21 groups, 10 animals per group, and irradiated with whole body gamma-irradiation of 1, 5, 10, 15, and 20 Gy. Samples of jejunum and transversal colon were taken 24, 48, 72, and 96 hours later, immunohisto-chemically stained, and the phospho-Elk-1 expression was examined using computer image analysis. A group of 10 sham-irradiated animals was used as control. Significantly increased expression of phospho-Elk-1 in rat jejunum has been found in all time intervals after irradiation by sublethal doses of 1 and 5 Gy, whereas after the irradiation by lethal doses, the expression of phospho-Elk-1 in rat jejunum varied considerably. Significantly increased expression of phospho-Elk-1 in transversal colon has also been found in the first days after irradiation by sublethal doses of 1 and 5 Gy. After irradiation by lethal doses, there was no uniform pattern of the changes in the expression of phospho-Elk-1 in rat transversal colon. The detection of phospho-Elk-1 might be considered as a suitable and very sensitive biodosimetric marker of radiation-induced injury of small and large intestine. According to our knowledge, this is the first study on the phospho-Elk-1 expression in irradiated jejunum and transversal colon in the rat.

Morphological changes of rat jejunum after whole body gamma-irradiation and their impact in biodosimetry.

Gastrointestinal form is the second stage of the Acute Radiation Syndrome (ARS) with a threshold dose of 8 Gy. It represents an absolutely lethal clinical-pathological unit, enteritis necro-hemorrhagica (duodenitis, jejunitis, ileitis, respectively) with unknown causal therapy. The purpose of our study has been to evaluate the morphological changes in a model of radiation-induced enteritis in rats and estimate the significance of changes in biodosimetry. Wistar rats were randomly divided into 21 groups, 10 animals per group. Samples of the jejunum were taken 24, 48, 72, and 96 h after the whole-body gamma-irradiation with the doses of 1, 5, 10, 15, and 20 Gy, and routinely stained with hematoxylin and eosin. Five morphometric markers--intercryptal distance, enterocytal height on the top and base of villus, length of basal lamina of 10 enterocytes and enterocytal width--in irradiated rat jejunum were examined. The results were compared with sham-irradiated control group. After lethal doses of irradiation, all morphometric parameters of jejunum significantly changed. With the exception of intercryptal distance, they might be considered as suitable biodosimetric markers under these experimental conditions. Our morphometry results in radiation-induced jejunitis are in accordance with those in other studies. We were the first who quantified morphological post-irradiation changes in animal jejunum. Some of them might be used under experimental conditions. This experimental study is a predecessor of the clinical assessment of a specific marker. Under clinical practice, the sensitive biodosimetric parameter could serve as one of the guidance for evaluation of the absorbed dose in irradiated troops as well as rescue workers. This is in accordance with tasks and Standardization Agreement of the North Atlantic Treaty Organization.

CD27(+) peripheral blood B-cells are a useful biodosimetric marker in vitro.

The CD8(+) natural killer (NK) subpopulation has recently been identified as a fast and reliable biodosimetric indicator within human peripheral blood mononuclear cells (PBMC) in vitro. In irradiated and subsequently cultivated PBMC, a decrease of the relative number of intact CD3(-)CD8(+) lymphocytes 16 and 48 h after treatment has allowed for estimating the received dose in the range of 0 - 10 Gy and lethal/sublethal dose discrimination, respectively. Here we show that suitable biodosimeters can also be found in the peripheral blood B-cell compartment. Multiparameter flow cytometric analysis of irradiated and subsequently cultivated human PBMC revealed that both the CD27(+) and CD21(-) B-cell subpopulations can be used as biodosimeters and the CD19(+)CD27(+) lymphocytes have proved useful for retrospective determination of the received dose in the range of 0 - 6 Gy. In addition, several CD19(+) lymphocyte subsets characterized by co expression of CD21, CD27 and CD38 have been shown to bear biodosimetric potential, too. However, when important parameters like the original size within the CD19(+) compartment, its radiation-induced changes and data variation had been taken into account, the CD27(+) subpopulation proved superior to the other B-cell subpopulations and subsets. It appears that, in the dose range of 0 - 6 Gy, the relative decrease of CD27(+) B lymphocytes provides more sensitive and reliable data than that of CD8(+) NK-cells due mainly to lower data variation. In contrast to CD27(+) B cells, the proportions of CD27(+) subpopulations of T-cells were not affected by irradiation. We have also proposed a simple experimental protocol based on full blood cultivation and three-color CD27/CD3/CD19 immuno-phenotyping as a time-saving and inexpensive approach for practical biodosimetric evaluations on simple, three-to-four color flow cytometers.

[Analysis of a group of HIV positive women who gave birth in the Czech Republic]. / Analýza souboru HIV pozitivních rodicek v Ceské republice.

OBJECTIVE: An analysis of HIV positive women who gave birth between 1st January 1985 to 31st December 2006 in the Czech Republic. SUBJECT: A retrospective descriptive analysis. SETTING: Teaching Hospital Bulovka, 1st Faculty of Medicine, Charles University, Prague. SUBJECT AND METHODS: The study included HIV positive women that gave birth between 1st January 1985 to 31st December 2006 at Bulovka hospital. The group of 62 HIV positive women (including 7 secundiparae) gave birth to 71 new-borns (twice twins). The deliveries were performed by C-section. We interrupted breast-feeding by all these women. RESULTS: All new-borns were born alive, no one had Apgar score less than 7 at five minutes. No congenital disorders were found. Three new-borns were transfered to Intensive care unit for new-born babies, two due to dysmaturity and one due to abstinence syndrome. 3 new-borns out of total 71 new-borns were HIV positive (4.2%). CONCLUSION: Routine prenatal screening for HIV and high-quality cooperation between obstetricians and infection control doctors are the basic condition of low rate of vertical trasmission HIV infection in the Czech Republic.

[Choroid plexus cysts and risk of trisomy 18. Modifications regarding maternal age and markers]. / Cysty choroidálního plexu a riziko trizomie 18. Modifikace ve vztahu k veku a markerum.

OBJECTIVE: Our aim was to evaluate the risk of chromosomal abnormalities esp. trisomy 18, associated with isolated choroid plexus cyst(s) in pregnant women undergoing second-trimester ultrasonographic examination. DESIGN: A review article. SETTING: OBGYN clinic of the 1st faculty of medicine, Prague, Teaching hospital Bulovka. SUBJECT: Choroid plexus cyst(s) (CPC) are more common in fetuses with chromosomal aneuploidies, particularly trisomy 18. Although it is accepted that the risk of karyotypic abnormality justifies amniocentesis in the case of other associated abnormalities are present, disagreement continues as to the risk of trisomy 18 in a fetus with an isolated choroid plexus cyst. We evaluated additional consideration of maternal age and multiple-marker screening for chromosomal aneuploidy in the assessment of risk. CASE REPORT: We report a trisomy 18 case that was diagnosed on the basis of CPC detection by ultrasound, NMR, and further amniocentesis. CONCLUSION: It is well accepted that choroid plexus cyst(s) in association with other congenital anomalies warrant amniocentesis to determine fetal karyotype. The presence of isolated CPC varies around 1% in general population, but around 30% in fetuses with trisomy 18 where the prevalence is 3 per 10,000 pregnancies. Metaanalyses reported incidence of trisomy 18 of 1 in 374 in fetuses with isolated CPC. These risks do not exceed the 1:200 risk of pregnancy loss after amniocentesis and also the 1:270 risk of Down syndrome (DS) in a 35-year-old woman, but exceeds the risk for DS of a 37-year-old woman. Thus these findings suggest that amniocentesis should not be offered to pregnant women in the presence of isolated fetal choroid plexus cyst(s), but in the absence of other pathologies. Amniocentesis is then justified only in the patient with advanced maternal age.