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Polypoid endometriosis is a very rare form of endometriosis, mostly affecting perimenopausal women and causing different symptoms than the usual type. It forms polypoid masses that can be misdiagnosed as malignant tumors during patient management. Polypoid endometriosis arising from a cyst wall is even more rare. Here, we present a case of a 47-year-old perimenopausal patient with a large cystic tumor in the left adnexal region and an inhomogenous tissue in the uterine cavity. Hysterectomy and bilateral adnexectomy was performed. The histology showed a polypoid endometriosis growing in an endometriotic cyst and, simultaneously, a large endometrial polyp with similar structure in the uterine cavity. Our case is unique because of the extreme rarity of polypous endometriosis in an endometriotic cyst and its even more rare association with an intrauterine endometrial polyp.

Problem This prospective study was aimed to evaluate whether non-invasive clinical and serologic parameters of tubal disease are predictive for subsequent spontaneous conception and pregnancy outcome after first episode of ectopic pregnancy (EP). Method of study Overall, 144 women aged

The aim of the study was to determine the effect of postmenopausal hormone replacement therapy (HRT) (treatment using estrogen only and sequential and continuous combined estrogen-progestogen treatment) on endometrial bleeding and histological changes of the endometrium. In a six-year period (2000–2005), 5893 patients were given care and the incidence of postmenopausal uterine bleeding was detected in groups of patients having and not having received hormonal treatment at the Menopause Out-patient Unit of the authors’ department. In the case of bleeding, fractioned abrasion was performed and the samples were analyzed histologically. Among the postmenopausal patients who had not been given hormonal treatment, the incidence of bleeding episodes was significantly higher as among those having received hormonal treatment. In the samples, findings of proliferative endometrium occurred significantly more often in case of non-treated patients and those treated with sequential combined hormone therapy compared to patients receiving continuous combined hormone therapy. Although it was statistically not significant, hyperplasia simplex and complex together showed a tendency of reduced incidence in patients medicated by continuous combined treatment. These findings suggest that continuous combined hormonal treatment started at the right time (even before the menopause) may reduce the chances of the development of hyperplasia. A significantly higher incidence of hyperplasia was noted in patients using estrogen treatment only. It is possible that unopposed estrogen treatment further engraves an already diagnosed endometrial hyperplasia. In the group having received hormonal treatment, no complex hyperplasia accompanied by atypia occurred, only hyperplasia simplex was diagnosed in these cases. As a result of continuous reliance on combined preparations, the endometrium had become atrophied, therefore the chance of hyperplasia-related changes and of bleeding as a side effect decreased significantly. According to the authors’ experience, hormonal treatment does not pose a risk to the development of endometrial carcinoma; on the contrary, continuous combined preparations appear to reduce the risk of hyperplasia and, indirectly, the chances of the development of adenocarcinoma.

Cékitűzés: A vizsgálat célja meghatározni a postmenopausalis hormonterápia (kizárólagos ösztrogén-, szekvenciális és folyamatosan kombinált ösztrogén-progesztogén kezelés) hatását az endometrialis vérzésre és a méhnyálkahártya szövettani átalakulására. Beteganyag: Szerzők klinikájának Menopauza Ambulanciáján ötéves időszakban (2000–2005) 5893 beteget gondoztak, és vizsgálták a postmenopausalis méhvérzések előfordulását a hormonterápiában részesültek és nem részesültek csoportjában. Vérzés esetén mindig frakcionált abrasiót végeztek, és a mintákat szövettanilag feldolgozták. Eredmények: A postmenopausában lévő betegek hormonkezelésben nem részesítettek csoportjában több mint kétszer több vérzés fordult elő, mint a hormonkezelésben részesültek között. Anyagukban a proliferatiós és a hyperplasiás endometrium-leletek elsősorban a nem kezelt páciensek közül kerültek ki, ami amellett szól, hogy a megfelelő időben, akár már a menopausa előtt megkezdett hormonkezelés csökkentheti a hyperplasia és ezáltal közvetve az adenocarcinoma kialakulásának az esélyét. A kizárólag ösztrogént alkalmazó betegekben gyakoribb volt a hyperplasia. Elképzelhetőnek tartják, hogy az ellensúlyozatlan ösztrogénkezelés a már meglévő endometrium-hyperplasiát tovább súlyosbíthatja. A hormonkezeltek csoportjában atípiával járó komplex hyperplasia nem, csak simplex hyperplasia fordult elő. A folyamatosan kombinált készítmények alkalmazása mellett az esetek döntő részében a méhnyálkahártya atrófizálódott, így lényegesen csökkent a hyperplasiával járó eltérések s a mellékhatásként jelentkező vérzés esélye. A hormonkezeltek között gyakoribb volt az endometrium-polip, és nem tudják megmagyarázni, de a cervicalis polypusok aránya is. Következtetés: A szerzők tapasztalata szerint a hormonkezelés nem rizikótényezője az endometrium-karcinómának, hanem a kombinált készítmények a hyperplasia és ezen keresztül az adenocarcinoma eredeti esélyét csökkentik.

Bevezetés: A szerzők célja, hogy Magyarországon először beszámoljanak egy ritka bőrbetegség, az acne inversa szeméremtesten megnyilvánuló, súlyos formájának radikális vulvectomiával történő sikeres kezeléséről. Esetismertetés: Egy 56 éves nőbeteg 30 éve fennálló acne inversa betegsége az ambuláns kezelések és többszöri hospitalizáció ellenére progrediált, és a szeméremtestet jelentősen torzító elváltozáshoz vezetett. A roncsolt szeméremtest eltávolítása radikális vulvectomia útján esztétikailag és az életminőség javítása szempontjából is eredményes volt. A szerzők az eset kapcsán ismertetik az acne inversa kóreredetének, differenciáldiagnosztikájának és kezelésének alapjait. Következtetés: A közlemény célja rámutatni arra, hogy a diagnózis felállításának és a sikeres kezelésnek alapfeltétele a társszakmák közötti szoros együttműködés.

Absztrakt A dializált betegek számának növekedési ütemét a transzplantációk száma, a donor szám lassú növekedése miatt nem tudja követni. A használható szervek számának növelésére a rokon és nem rokon élő donorok szervei használhatóak, valamint meghatározott feltételek mellett marginális donorok (extended criteria donors) veséi. Ezen utóbbi veséknél a megfelelő funkció eléréséhez a donor mindkét veséjének egy recipiensbe való beültetése szükséges. A Texasi Egyetem transzplantációs osztályán két év alatt 5 betegnél végeztünk kettős vese beültetést olyan szervek felhasználásával, melyeket hagyományos transzplantációra egyik transzplantációs osztály sem fogadott el. A veséket egyoldalra, retroperitonealis feltárásból, a fossa iliacaba helyeztük. A recipiensek átlag életkora 44.4 év volt, két beteg a magas immunologiai rizikó csoporthoz tartozott. A beültetés után mind az 5 betegnél azonnali veseműködést észleltünk. Az átlagos kórházban tartózkodási idő (6.25 nap) alatt a transzplantációt megelőző 1000µmol/l feletti átlagos szérum kreatinin szint 350 µmol/l-re csökkent. A glomerulus filtrációs ráta (GFR) 7 ml/percről 41 ml/percre emelkedett. Két betegnél zajlott, a vesefunkciót is lényegesen rontó akut rejekció. A kétéves követési idő alatt egyik betegünk sem igényelt hemodializist. Összefoglalva, a kettős vese transzplantáció jó megoldásnak ajánlható. Úgy gondoljuk, hogy következetes és megfontolt szelekcióval olyan vesék – amelyek önmagukban nem volnának képesek megfelelő vesefunkció biztosítására – kettős vese beültetésként felhasználásra kerülhetnek.

Human papillomavirus (HPV) is known as a strictly epitheliotropic pathogen. Our results raised the possibility that HPV 16 is present in neural cells and in the vascular endothelium. By in situ hybridization, we have detected HPV 16 E6 ORF sequence in small blood vessels and peripheral nerves adjacent to oral and cervical cancers. The same structures have clearly shown immunohistochemical reactivity for the E6 oncoprotein. These results were verified by PCR applied to E6 and L1 ORFs following microscopic laser dissection of the immunohistochemically positive nerves and vessels.These observations suggest that HPV 16 DNA and protein are present in neurons and endothelial cells in the vicinity of HPV-associated tumors. The HPV 16 genome presumably exists in a non-replicating form in the neurons and constitutively produces high levels of E6 and E7 proteins with an unknown neuropathological outcome.

In this study, we investigated the presence of high-risk (HR) HPV types most prevalent in the Hungarian population in surgically removed cervical cancers and pelvic lymph nodes. The aim of our work was to determine the prognostic significance of HPV status in the lymph nodes draining the tumor.Primary tumor specimens from 150 patients and 900 lymph node samples (six per case) were studied. Fifty-six/150 were early (FIGO IA-IB) stage, while 94/150 were advanced (FIGO IIA-IIIB) stage cancers. Beside histopathological evaluation, DNA extracted from the tissue samples was subjected to nested PCR to detect characteristic type-specific sequences of HPVs 16, 18 and 33. Moreover, clinicopathological data were collected for an average 48-month postoperative follow-up period for the purposes of statistical analysis.The presence of HR-HPV types in the lymph nodes shows no correlation with disease-free survival, whereas the presence of lymph node metastases significantly decreases life expectancy (P = 0.002). Lymph nodes with metastases more frequently carry HR-HPV than nodes with no evidence of tumorous infiltration (65% versus 36%, P0.001); however, a high number of metastases surrounding HR-HPV-positive tumors were found negative for the viruses (42/120).HR-HPV status of pelvic lymph nodes draining cervical cancers has no noticeable influence on the life expectancy of the patients. HR-HPV-positive tumor cells do not necessarily have a selective advantage in forming metastases. Presumably, a number of alterations in cellular genes rather than the presence of papillomavirus DNA may have a decisive role in the progression of cervical cancers.

OBJECTIVES: Polymorphic regions of the dopamine D4 receptor gene and its promoter region are in the focus of psychogenetic association studies. Besides the accurate phenotype characterization, highly reliable genotyping methods are also of outstanding importance in these works. METHODS: DNA samples of 598 healthy unrelated Caucasian individuals were used to validate the described molecular haplotyping methods and to determine the allele, genotype and haplotype frequencies and the linkage disequilibrium between the polymorphisms of the dopamine D4 receptor promoter region. RESULTS: We described a double genotyping system for the -521CT and -616CG polymorphisms, using a polymerase chain reaction restriction fragment length polymorphism or an allele-specific amplification. Allele and genotype frequencies of the novel -615AG single-nucleotide polymorphism are also determined (-615G=13.21%). For molecular haplotyping of the three single-nucleotide polymorphisms and a 120-bp duplication polymorphism, the allele-specific amplification was combined with restriction digestion. The results of the elaborated haplotyping methods were validated by molecular haplotyping of cloned fragments. CONCLUSIONS: The developed methods have been arranged into an 'economic' protocol that might be extended for higher reliability with a double haplotyping ('full mode'). Despite the close proximity of these sites, only a moderate linkage was found between the -615AG and -616CG (Delta(2)=0.162), between the -616AG and -521CT (Delta(2)=0.0221) and between the -615AG and -521CT single-nucleotide polymorphisms (Delta(2)=0.0346). The 120-bp duplication was shown to be in linkage equilibrium with any of the three single-nucleotide polymorphisms. Applications of these results should accelerate psychogenetic association studies of the dopamine D4 receptor gene.

Deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, plays a seminal role in the bioactivation of a wide array of cytotoxic nucleoside analogues. Recently, activation of dCK has been considered as a protective cellular response to a number of DNA-damaging agents in lymphocytes. Regarding the molecular mechanism of the enzyme activation, a post-translational modification by protein phosphorylation has been suggested. Here we provide evidence that both the activation process and the maintenance of the activated state require free cytosolic calcium. BAPTA-AM, a cell-permeable calcium chelator selectively inhibited the activation of dCK in a time- and concentration-dependent manner while extracellular calcium depletion had no effect. On the other hand, elevation of cytoplasmic calcium levels by thapsigargin did not potentiate the enzyme, referring to the permissive function of calcium in the activation process. Denaturing Western blots of extracts from lymphocytes incubated with 2-chlorodeoxyadenosine, aphidicolin and/or BAPTA-AM clearly demonstrated that dCK protein levels were unchanged during these treatments. However, a striking correlation was found between enzyme activity and the intensity of dCK-specific signals in native Western blots. Extracts from CdA-treated cells were much better recognized by the antibody raised against the C-terminal peptide of dCK than the BAPTA-AM-treated samples. These results indicate that the calcium-dependent activation of dCK is accompanied by a conformational change that renders the C-terminal epitope more accessible to the antibody.

Deoxycytidine kinase (dCK) is a key enzyme in the intracellular metabolism of deoxynucleosides and their analogues, phosphorylating a wide range of drugs used in the chemotherapy of leukaemia and solid tumours. Previously, we found that activity of dCK can be enhanced by incubating primary cultures of lymphocytes with substrate analogues of the enzyme, as well as with various genotoxic agents. Here we present evidence that exposure of human lymphocytes to 0.5–2 Gy dosage of γ-radiation as well as incubation of cells with calyculin A, a potent inhibitor of protein phosphatase 1 and 2A, both elevate dCK activity without changing the level of dCK protein. When cells were gamma-irradiated in the presence of calyculin A, a more pronounced activation of dCK was observed. In contrast, both basal and stimulated dCK activities were reduced by hyperosmotic treatment of the cells. DNA repair determined by the Comet assay and by thymidine incorporation was induced by irradiation. Complete repair of γ-irradiated DNA was detected within 1 hr following the irradiation along with dCK activation, but the rate of repair was not accelerated by calyculin A. These data provide evidence for the activation of dCK upon DNA damage and repair that seems to be mediated by phosphorylation of the enzyme, suggesting the role of dCK in DNA repair processes.

Introduction Primary non-Hodgkin's lymphoma of the uterine cervix is a rare malignancy. The mainstay of therapy consists of irradiation alone or irradiation with either surgery or chemotherapy. Case report We present the case of a 56-year-old woman diagnosed with a bulky, Ann Arbor stage IE, primary, diffuse, large B-cell non Hodgkin's lymphoma of the uterine cervix. We administered neoadjuvant chemotherapy according to CHOP protocol (cyclophosphamide, adriamycin, vincristine, and prednisone) followed by radical hysterectomy, bilateral salpingo-oophorectomy, and regional lymph node dissection. Clinical and pathological responses to the chemotherapy were complete. The patient is alive 5 years after the initial diagnosis. Conclusion Our case emphasizes the importance of neoadjuvant chemotherapy that can provide a control of the distant microscopic metastases.

Epignathus is a rare congenital orofacial teratoma. We present a case of a fast-growing tumor, where early prenatal diagnosis was made and where fetopathological examination revealed the reason of the remarkable ultrasonographic signs and underlined the expected poor prognosis. Ultrasonographic examination at 18 weeks' gestation showed that there was a growing tumor protruding from the fetus's mouth. The fetal stomach could not be seen and extreme polyhydramnios was also detected. After counseling, the couple opted for a termination of pregnancy. Fetopathological examination showed that the tumorosus mass was not only protruding from the mouth, but also inexplicably grew downwards, was connected to the hard palate and the periosteum of the vertebral corpus, making an airway and esophageal obstruction, causing the ultrasonographic findings. Postnatal treatment and surgical removal of this tumor seemed to be impossible. In case of an early detection of a fast-growing fetal epignathus, pregnancy termination should be considered.

Deoxycytidine kinase (dCK) is one of the key enzymes of deoxynucleoside salvage supplying resting lymphocytes with DNA precursors for synthesis and repair. The level of dCK activity is especially important in chemotherapy with the use of deoxynucleoside analogues like arabinosyl cytosine (Citarabid, ara-C), or 2-chloro-deoxyadenosine (Cladribine, CdA). Previous results showed that Cladribine treatment of human lymphocytes increased several fold the activity of dCK without increasing the amount of dCK protein itself (Sasvári-Székely, et al., 1998, Biochem. Pharmacol. 56, 1175), and a possible post-translational modification was suggested. This theory was further investigated using NaF as an inhibitor of protein phosphatases. It was shown that NaF treatment of cells elevated dCK activity while inhibiting DNA synthesis. The possible mechanism of dCK activation/inactivation induced by exposure of cell cultures to different agents is discussed.

Deoxycytidine kinase (dCK, EC.2.7.1.74) is a key enzyme in the intracellular metabolism of 2-chlorodeoxyadenosine, 1-β- d -arabinofuranosylcytosine, difluorodeoxycytidine, and other drugs used in chemotherapy of different leukaemias and solid tumours. Recently, stimulation of dCK activity was shown by these analogues and by other genotoxic agents such as etoposide and NaF, all of which cause severe inhibition of DNA synthesis in cell cultures. Here we describe that direct inhibition of DNA polymerases by aphidicolin stimulated dCK activity in normal lymphocytes and acute myeloid leukaemic cells, as well as in HL 60 promyelocytic cell cultures. Increased dCK activity was not due to new protein synthesis under our conditions, as measured by immunoblotting. Partial purification by diethylaminoethyl–Sephadex chromatography revealed that the activated form of dCK survived purification procedure. Moreover, it was possible to inactivate purified dCK preparations by recombinant protein phosphatase with Ser/Thr/Tyr dephosphorylating activity. These data suggest that the activation of dCK may be due to phosphorylation, and that deoxynucleoside salvage is promoted during inhibition of DNA synthesis in human lymphocytes.

Gel electrophoresis is one of the most frequently used tools for the separation of complex biopolymer mixtures. In recent years, there has been considerable activity in the separation and characterization of protein molecules by sodium dodecylsulfate (SDS) gel electrophoresis with particular interest in using this technique to separate on the basis of size and to estimate molecular mass and protein purity. Although the method is informative, it is cumbersome, time consuming and lacks automation. In this paper we report an automated, high-performance SDS gel electrophoresis system that is based on electric-field-mediated separation of SDS-protein complexes using an ultra-thin-layer platform. The integrated fiber optic bundle-based scanning laser-induced fluorescence detection technology readily provided high sensitivity, real-time detection of the migrating solute molecules. Rapid separations of covalently and non-covalently labeled proteins were demonstrated in the molecular mass range 14,000 to 205,000 in less than 9 and 16 min, respectively. Excellent quantitation and lane-to-lane migration time reproducibility were found for all the solute components using the multilane separation platform. The limit of detection was found to be 1.5-3 ng/band for both labeling methods, with excellent linearity over a six times serial double-dilution range. Molecular mass calibration plots were compared for both covalently and non-covalently labeled proteins. A linear relationship was found between the molecular mass and electrophoretic mobility in the case of covalently labeled samples, while a non-linear relationship was revealed for the non-covalently labeled samples.

Deoxycytidine kinase (dCK, EC.2.7.1.74), a key enzyme in intracellular metabolism of many antileukemic drugs, was shown to be activated during treatment of lymphocytes by 2-chloro-2'-deoxyadenosine (Cl-dAdo, cladribine), a potent inhibitor of DNA synthesis. While 5-[3H]-thymidine (TdR) incorporation into DNA was decreased by 80-90%, dCK activity was doubled as a consequence of incubating the cells with 1 microM 2-chloro-2'-deoxyadenosine. Thymidine kinase (dTK, EC.2.7.1.21) activity was slightly decreased under the same conditions, similarly to 5-[3H]-thymidine incorporation. dCK activation could not be prevented by cycloheximide, and neither the amount of dCK protein nor its mRNA level was increased after 2-chloro-2'-deoxyadenosine treatment. These results suggest a post-translational activation of dCK protein during inhibition of DNA synthesis.

Fetal pericardial effusion usually develops because of fetal heart failure, infections, chromosomal abnormalities, fetal anaemia, intracardiac or extracardiac tumours. There is only one case in the literature of isolated hydropericardium associated with left ventricular diverticulum and here we report another.

Clinical and histopathological correlations of immunoreactivity to Chlamydia trachomatis and to epitopes of the C. trachomatis 60 kDa heat shock protein (hsp60) among women with ectopic pregnancy were evaluated in a case-control study. Serological responses to 13 synthetic peptides corresponding to major epitopes of the chlamydial hsp60 were determined in 67 women treated for ectopic pregnancy and 45 women with uncomplicated pregnancy in utero. Plasma cell salpingitis was detected in 29 (43.3%) of the ectopic patients. Its presence correlated with antibodies to two hsp60 epitopes, encompassing amino acids 260-271 and 411-422 (P = 0.02). Antibodies to these two epitopes, along with five other epitopes, also correlated with peritubal adhesion formation in ectopic pregnant patients (P < 0.01). Antibodies to epitopes 260-271 and 188-199 also correlated with a history of pelvic inflammatory disease (PID; P = 0.05). Patients with ectopic pregnancy were also more likely than their intrauterine pregnant controls to have present anti-chlamydial immunoglobulin G (P < 0.005). Women positive for both C. trachomatis and hsp60 epitope antibodies had an increased prevalence over controls of salpingitis, pelvic adhesions or history of PID (P < 0.05). In contrast, patients who were positive for only C. trachomatis antibodies or only hsp60 epitope antibodies did not differ from antibody-negative patients in each of these categories.

A case of multifocal hemangioendothelioma of the liver, adrenal gland, and placenta is reported. The histological appearance of the tumor is consistent with an infantile hemangioendothelioma, type 2. Multifocal development is the most obvious explanation for the disease but the possibility that this represents malignant placental neoplasm with metastases requires consideration.

Epignathus is a rare congenital orofacial teratoma. We present a case of a fast-growing tumor, where early prenatal diagnosis was made and where fetopathological examination revealed the reason of the remarkable ultrasonographic signs and underlined the expected poor prognosis. Ultrasonographic examination at 18 weeks' gestation showed that there was a growing tumor protruding from the fetus's mouth. The fetal stomach could not be seen and extreme polyhydramnios was also detected. After counseling, the couple opted for a termination of pregnancy. Fetopathological examination showed that the tumorosus mass was not only protruding from the mouth, but also inexplicably grew downwards, was connected to the hard palate and the periosteum of the vertebral corpus, making an airway and esophageal obstruction, causing the ultrasonographic findings. Postnatal treatment and surgical removal of this tumor seemed to be impossible. In case of an early detection of a fast-growing fetal epignathus, pregnancy termination should be considered.

Cantrell’s pentalogy is a rare multiple malformation syndrome consisting of supraumbilical abdominal wall defect, sternal defect, pericardial defect, anterior diaphragmatic defect and heart malformation. Aims and methods: Prenatal ultrasound findings and malformations described during autopsy of the Cantrell’s pentalogy cases diagnosed between January 1991 and June 2009 in our institute were reviewed. A literature research was conducted to analyze the prevalence and prenatal detection rate of the five previously described malformations and ectopia cordis in the Cantrell’s pentalogy cases. Results: Six cases of Cantrell’s pentalogy were diagnosed during the study period in our department. Sonography detected multiple malformations in 3 cases, and isolated malformation in 3 cases. Analyzing the data of 49 Cantrell’s pentalogy cases altogether showed that, beside abdominal wall defect and ectopia cordis which had the highest prenatal detection rate (83% and 91% with a prevalence of 94% and 69%, respectively), sternal defect and anterior diaphragmatic hernia were also present in a large number of the cases (80% and 73% respectively). Conclusion: Sonographic identification of the sternal defect or diaphragmatic hernia may help to differentiate Cantrell’s pentalogy from malformations part of the syndrome but occurring as isolated defects.

Conception sometimes results in products that are not capable of developing into an embryo and fetus. This group, designated with the term gestational trophoblastic neoplasia, comprises the benign hydatidiform mole, the invasive mole (chorioadenoma destruens) and the frankly malignant variety, choriocarcinoma. Another type of atypical oocyte activation occurs in parthenogenesis. In the human, two types of tumors, dermoid cysts and teratomas, can result from this process. The authors of this paper aim to elucidate the mechanisms how these abnormal growths ensue and provide explanations why they cannot be regarded as human individuals or human beings. They conclude that it is not the exact number of chromosomes that is required for a form of human life to become a human being but rather the biparental origin of the chromosome set.

This prospective study was aimed to evaluate whether non-invasive clinical and serologic parameters of tubal disease are predictive for subsequent spontaneous conception and pregnancy outcome after first episode of ectopic pregnancy (EP).Overall, 144 women aged35 years were enrolled. Outcome of subsequent spontaneous conception was analyzed after 3 years and compared with clinical parameters and antibody responses to Chlamydia trachomatis and epitopes of the 60-kDa chlamydial heat shock protein (CHSP-60).Antibody response to a conserved epitope of CHSP-60 (amino acids, aa 260-277) was independently correlated with both decreased spontaneous conception and term delivery rates (adjusted odds ratios, OR: 3.6 and 5.4, respectively).Presence of circulating antibodies to a conserved epitope of the CHSP-60 is associated with a lower spontaneous conception rate, and increased likelihood of adverse pregnancy outcome in women treated by salpingectomy for first episode of EP.

The human dopamine D4 receptor (DRD4) gene has been extensively studied as a candidate gene for attention deficit hyperactivity disorder (ADHD). Both the 5' regulatory region and the coding sequence contain a number of polymorphisms. The most widely investigated polymorphism of the DRD4 gene is the 48 bp VNTR (Variable Number of Tandem Repeats) in the third exon. The promoter variants have received particular attention in the past few years due to their possible role in the regulation of gene expression. In this study we describe an association analysis of the 120 bp duplication and three sequence variations (SNPs, Single Nucleotide Polymorphism; -616 C/G, -615 A/G, -521 C/T) in the 5' region of the DRD4 gene is presented among children with ADHD. In case-control approach, the 1-repeat form of the 120 bp duplication had a significantly higher frequency among ADHD children than controls, both in allele-(p=0.047), and genotype (p=0.019) distributions. There was no significant difference between the ADHD and control groups in the allele or genotype frequencies of the investigated SNPs. The transcriptional effect of the 120 bp duplication was analysed in luciferase reporter system. The different 120 bp duplication alleles (1-repeat, 2-repeat and the newly identified 4-repeat allele) was found to have an effect on transcriptional activity of the DRD4 gene in both neuroblastoma and retinoblastoma cell lines in a dose-dependent manner. The higher was the repeat number of the 120 bp sequence in the promoter, the stronger was the decrease of the gene transcription (1-repeat2-repeat4-repeat; p0.01). These results of association and functional analyses suggest that the 1-repeat form of the 120 bp duplication might be a risk factor of ADHD.

The patients number on the transplant waiting lists are continuously increasing. The number of donors and transplantations can not reach this acceleration. To increase the number of organs we can use living donor organs or carefully selected extended criteria organs. To achieve appropriate function with marginal donor kidneys we need to transplant both kidneys into the same recipient. At the Transplant Division of University of Texas during a two years period we performed 5 double kidney transplantations with organs refused by the local transplant services. We placed both kidneys to the same side, retroperitoneally. The recipients mean age was 44.4 years and two of them belonged to the immunological risk ethnic group. After the transplantation all kidneys showed immediate function. During the patients mean hospital stay (6.25 days) the serum creatinine level decreased from 1000 micromol/l to 350 micromol/l. The Glomerular Filtration Rate (GFR) increased from 7 ml/min to 41 ml/min. Two patients suffered acute rejection which influenced their kidney function. During our two year follow up all patients avoided haemodyalsis. Double kidney transplantation is an acceptable solution for expanding the donor pool. After consistent and cautious selection previously rejected kidneys can be used.

Abnormalities of the dopamine neurotransmission have been hypothesized to play an important role in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Promoter variants of the dopamine D4 receptor gene (DRD4) have attracted particular interest due to their possible role in regulation of gene transcription. Here we describe the haplotype analysis of the 120 base pair duplication (120-bp dup) and three SNPs (-616C/G, -615A/G, -521C/T) in the 5' region of the DRD4 gene among children with ADHD. We observed a trend (chi(2) = 14.905, df = 9, P = 0.093) in the four-locus haplotype distribution between ADHD probands (N = 173) and controls (N = 284). The homozygote genotype of the 1-repeat form of the 120-bp dup (1-1) had a significantly higher frequency among ADHD children than in controls (8.1% vs. 3.2%, chi(2) = 5.526, df = 1, P = 0.019, Odds Ratio = 2.71). In addition, a novel, 4-repeat allele was identified among ADHD patients. This particular allele has been cloned to the luciferase expression vector and its transcriptional activity has been compared to the 1- and 2-repeat allele. The number of repeats of the 120-bp dup was found to have an effect on transcriptional activity in both neuroblastoma and retinoblastoma cell lines in a dose-dependent manner (1-repeat > 2-repeat > 4-repeat). These results suggest that the 1-repeat form of the 120-bp dup might be a risk factor of ADHD, especially in the homozygous form and/or in the context of certain haplotypes.

Congenital absence of the ductus venosus is a rare anomaly. The authors have found 57 cases in the literature. Their case was associated with a complex congenital heart disease, what occurs only in 10% of absent ductus venosus cases. In cases, where the umbilical vein connects directly to the right atrium, the volume overloading causes dilatation of the right atrium and ventricle, development of polyhydramnios and fetal hydrops. The diagnosed an umbilical vein directly connected to the right atrium, extreme systemic congestion, but no hydrops. In some fetuses this condition did not result hydrops, because there is compensation by the rich compliance of intrahepatic vascular beds. This case is an illustration that mild sonographic signs such a transient bradycardia in the early second trimester could be a sign of a heart malformation and can draw attention of the sonographer to other associated severe congenital heart disease.

Objectives This study was conducted to compare the prenatal ultrasound findings and postmortem pathologic findings of fetuses with trisomy 13. Methods Of 22 150 fetal chromosome analyses, 28 fetuses with trisomy 13 were diagnosed between 1990 and 2004. Findings of second-trimester sonography and subsequent fetal autopsy were compared by organ system, and their correlation was assigned to one of three categories based on the degree of agreement. Results Of the total of 79 abnormalities that were found on autopsy, prenatal sonography showed 48 (60.8%). The agreement was more than 75% of all abnormalities of these systems: central nervous system (CNS) (76.5%), facial abnormalities (76.5%), urinary system (81.8%) and fetal hydrops (100%), whereas the sensitivity of sonography was lower in these organ systems: heart (53.3%), extremities (12.5%) and abdominal abnormalities (33.3%). In 39.2% of the cases, autopsy findings were not detected by sonography. These additional findings at autopsy involved mainly three organ systems: heart, face and extremities. Some ultrasound findings (n = 17) were not verified at autopsy; most of them were quantitative markers (mild ventriculomegaly, mild pyelectasis). Conclusion Our results indicate that thorough sonographic examination of the fetal face (including ears) and extremities (including hands and feet) with an extensive use of fetal echocardiography may increase the sensitivity of prenatal sonography in detecting trisomy 13. Copyright © 2006 John Wiley & Sons, Ltd.

Previously, we have found that activation of deoxycytidine kinase elicited by various DNA-damaging chemical agents could be prevented by BAPTA-AM, a cell-permeable calcium chelator or by pifithrin-alpha, a pharmacological inhibitor of p53. Here, we show that stimulation of deoxycytidine kinase by UV-light also is calcium-dependent and pifithrin-alpha-sensitive in tonsillar lymphocytes, while thymidine kinase 1 activity is stabilised in the presence of BAPTA-AM. Importantly, both UV-irradiation and calcium chelation decreased the incorporation of labelled deoxycytidine and thymidine into DNA. Pifithrin-alpha dramatically reduced the labelling of both the nucleotide and DNA fractions, possibly due to inhibition of transmembrane nucleoside transport.

Aims: This study was designed to compare the prenatal ultrasound findings and postmortem pathologic findings of fetuses with trisomy 18. Study design: Of 22,150 fetal chromosome analyses, 70 fetuses with trisomy 18 were diagnosed between 1990 and 2004. Sonographic and perinatal autopsy findings were compared by organ system and their correlation was assigned to 1 of 3 categories. Results: There were 164 separate major structural abnormalities found on autopsy. Of them, sonography detected 72 (43.9%). Among major defects the agreement was more than 75% of all abnormalities of these systems: central nervous system (80%), abdominal abnormalities (87.5%) and cystic hygroma (100%). Whereas, the sensitivity of sonography was lower in these organ systems: cardiac system (66.6%), facial abnormalities (26.3%), urinary system (27.3%) and extremities (8.7%). The rate of additional findings at autopsy was 56.1% and involved mainly 2 organ systems: face (including ear) and extremities (including hands and feet). Some ultrasound findings (n=15) were not confirmed at autopsy in our series. Conclusions: This study confirms that perinatal autopsy provides additional information in many fetuses with trisomy 18. Besides obstetricians, pediatricians and geneticists, specialized perinatal pathologists have an important role in the multidisciplinary management of prenatally diagnosed fetal malformations. In addition, examining the correlation between sonography and pathologic findings may indicate potential markers for sonographic screening of trisomy 18.

The purpose of this study was to assess the 5-year survival and morbidity when radical hysterectomy and pelvic lymphadenectomy with pre- and postoperative radiation have been performed for IA2-IIB stage cervical cancer.During a 10 and a half year period between July, 1990 and December, 2000, 501 consecutive radical hysterectomies with bilateral pelvic lymphadenectomies were performed by the same gynecological surgeon for stage IA2, IB, IIA and IIB carcinoma of the cervix at the I. Department of Obstetrics and Gynecology, Semmelweis University Budapest. The patients were treated by pre- and postoperative irradiation as well.Perioperative complications apart from recurrence were minimal with no long-term morbidity. The absolute 5-year survival rates for the patients in stage IA2, IB1, IB2, IIA and IIB were 94,4%, 90,7%, 84,1%, 71,1% and 55,4%, respectively. The respective 5-year survival rates for patients without or with lymph node metastasis, were 94,5% and 33,3% in stage IB2, 81,7% and 48,7% in stage IIA and 70,2% and 36,5% in stage IIB, respectively.Nerve-sparing radical abdominal hysterectomy with pelvic lymph node dissection and pre- and postoperative irradiation remains the treatment of choice for most patients with early-stage and even in IIB-stage cervical cancer. The radicality and extent of lymph node dissection and parametrial resection should be individualized and tailored to tumor- and patient-related risk factors.

An abnormal course of the umbilical vein is a rare anomaly. Its association with the congenital absence of the ductus venosus is common. We found 3 cases of an abnormal course of the umbilical vein and an absent ductus venosus. In 2 of these cases, the umbilical vein turned down and continued in the internal iliac vein, and no ductus venosus was found. One of these pregnancies was terminated. From the continued pregnancy a growth-retarded baby was born. At follow-up examinations, mild microcephaly, mildly elevated levels of ammonia, delayed speech and mild muscular hypotonia were found. In the third case, the umbilical vein turned up from the level of umbilical ring and the anterior of the liver above the diaphragma and connected directly into the right atrium. Associated complex congenital heart malformations – transposition of the great arteries, and ventricular septal defect – were diagnosed prenatally. In the umbilical vein from the placenta to the umbilical ring, the flow was low velocity continuous; from the umbilical ring to the right atrium, the flow was biphasic high velocity (90 cm/s). Such an elevated blood flow could be a sign of increased cardiac preload. The long-term neurological follow-up of babies with prenatally diagnosed venous malformations is necessary.

Concerning our results, dCK seems to be the most important deoxynucleoside kinase in resting phase cells, or in cells with DNA damages to be repaired. The DNA damage might be induced by different nucleoside analogues, inhibitors of DNA synthesis. Deoxyadenosine and its analogues, their triphosphates are inhibitors of the DNA repair itself, might be pushing the corresponding salvage kinase in a “more” active form, probably by the secondary modification of the enzyme, to produce deoxynucleotides for repairing DNA.

In contrast to deoxycytidine kinase from leukemic blasts7, the recombinant dCK is a poor substrate for protein kinase C. Protein kinase A effectively phosphorylates the recombinant dCK. However, neither substrate specificity, nor kinetic parameters of dCK were changed upon phosphorylation. Nevertheless, treatment of partially purified lymphocyte dCK with recombinant phosphoprotein phosphatase completely destroys its phosphotransferase activity. These data suggest that phosphorylation plays a role in the regulation of lymphocyte dCK

The immunosuppressive agents have a broad spectrum of adverse effects. In the absence of selective and specific drugs the decrease incidence and severity of side effects can be achieved by the combination of synergistic drugs only. Without wise selection and use of the combination of the potent immunosuppressive agents for the immunosuppressive maintenance therapy better results cannot be achieved without or fewer toxicities particularly in high-risk patients who lose their grafts prematurely. Therefore, a good combination will allow not only to reduce individual immunosuppressive drug induced toxicities but will also allow to achieve better graft and patient survival.To assess the 6-year impact of a sirolimus-based regimen with, modest exposures to cyclosporine among three ethnic groups with different rejection risk, the authors performed a retrospective analysis of 470 renal transplant recipients who were treated contemporaneously: Group 1, high risk African Americans (n = 122); Group 2, moderate risk Hispanics (n = 132); Group 3, mild risk Caucasians (n = 216). Multivariate models were used to compare the outcomes in Group 1 with those of the other two groups.The cumulative incidence of acute rejection episodes over the entire follow-up period was similar among the groups: Group 1, 22.0%, Group 2, 24.2% and Group 3, 23.0%. Although there were no significant differences in overall or individual infection rates, Group 1 and 2 recipients displayed a significantly lower incidence of diarrhea at all times during follow-up compared with Group 3. All recipients showed similar rates of lymphocele formation. However, Group 1 displayed a reduced incidence and decreased severity of hypertriglyceridemia than Group 2 or Group 3 (89.3% vs. 97.2% vs. 93.2%), a similar incidence of hypercholesteremia (94.3% vs. 97.2% vs. 98.5%) was observed. The occurrence of post-transplant diabetes mellitus was greater in Group 1. than Group 3. but similar to Group 2.A concentration-controlled sirolimus-cyclosporine-prednisone regimen (with steroid withdrawal by 3 months) reduced the incidence of acute rejection episodes and increased 6-year graft survivals among high-risk African Americans to rates similar to other ethnic groups without an augmented toxicity profile.

We report herein findings on 181 patients, suffering from pelvic endometriosis confirmed by histology, whose main symptom was chronic pelvic pain (CPP). They attended the outpatient clinic at the 1st Department of Obstetrics and Gynaecology, Semmelweis University in Budapest, between 1 January 1995 and 1 January 2000. The extent of pelvic endometriosis was determined on the basis of the 1985 revised scoring system of the American Fertility Society (R-AFS). The short form of the McGill pain questionnaire was used for the evaluation of CPP. After the first operative intervention, therapy with a gonadotropin-releasing hormone (GnRH) analog was given for 6 months. Second-look laparoscopy was performed 8-10 weeks after the end of GnRH-analog treatment, which was followed by a non-conventionally administered, monophasic oral contraceptive (OC) treatment. In the long term, 118 patients received the non-conventionally administered, monophasic OC treatment, which contained a third-generation progestogen, to be taken continuously for at least 6 months. The other 63 patients who did not receive OC treatment for one reason or another were evaluated as a control group. We analyzed data on CPP before the first surgical intervention, then following therapy with the GnRH analog at the second-look operation, and then after 6, 12, 18 and 24 months. We also reviewed potential causes of CPP, especially focused on endometriosis. No correlation was found between the stage of endometriosis according to R-AFS score and the severity of CPP. At the 24-month follow-up after second-look laparoscopy, the non-conventionally administered monophasic OC treatment was found not only to significantly reduce pain scores, but also the required radical operative solution (hysterectomy plus bilateral adnexectomy) for CPP by OC users.

Stimulation of the activity of deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, has been recently considered as a protective cellular response to a wide range of agents interfering with DNA repair and apoptosis. In light of this, the potential contribution of dCK activation to apoptosis induction--presumably by supplying dATP or its analogues for the apoptosome formation--deserves consideration. Two-hour exposure of human tonsillar lymphocytes to 2-chloro-deoxyadenosine (CdA) led to a two-fold activation of dCK. This activation process was inhibited by pifithrin-alpha, a potent inhibitor of p53. When the dNTP pools were determined, both deoxypyrimidine triphosphate and dGTP pools were reduced after the treatments, while dATP levels elevated by 62%, 77% and 50% in the CdA, aphidicolin and etoposide-treated cells, respectively. We assume that dCK activation elicited by cellular damage might be a proapoptotic factor in terms of generating dATP well before the release of cytochrome c and deoxyguanosine kinase from mitochondria.