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Background and Study Aims: Colonoscopy screening for colorectal cancer has been implemented without evidence from randomized controlled trials quantifying its benefit and invariably as an opportunistic program, both of which are contrary to the European Union guideline recommendations. The aim of this paper is to describe the rationale and design of the first population-based colonoscopy screening program (PCSP), which was launched in Poland in 2012 as a randomized health services (RHS) study., Methods: The PCSP is a natural extension of opportunistic colonoscopy screening implemented in 2000. It uses colonoscopy capacity, a quality assurance program, and a network of 92 centers built up during the opportunistic screening phase to develop a countrywide PCSP. Within the PCSP, single screening colonoscopy is offered to a target population aged 55-64 years. The PCSP uses an RHS design, which means that eligible individuals drawn from population registries are randomly assigned to immediate or postponed invitation to screening. Individuals from birth cohorts that will reach the upper age limit for screening before full implementation of the PCSP are randomly assigned, in a 1:1:1 ratio, to "immediate" screening, "postponed" screening, or a "never invited" control group. The RHS design is a natural platform that will evaluate the effectiveness of screening, and compare different age ranges for screening, invitation procedures, and quality improvement interventions. Up to 2015, 24 centers have been developed, with 34.2% geographic coverage and 851,535 individuals enrolled., Conclusions: The PCSP sets an example for implementation of population-based colonoscopy screening with experimental design to ensure proper evaluation of its effectiveness., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The aim of present study was to assess the maternal serum endothelial nitric oxide synthase (eNOS), NOSTRIN (eNOS-trafficking inducer) and asymmetric dimethylarginine (ADMA) levels in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants., Patients and Methods: The study was performed on 65 normotensive pregnant women with isolated IUGR, 64 preeclamptic women with IUGR, 51 preeclamptic women with normal intrauterine fetal growth and 65 healthy normotensive pregnant women with singleton uncomplicated pregnancies. Severe preeclampsia was defined as blood pressure> 160/110 mmHg with proteinuria> 5 g in a 24-h urinary protein excretion. IUGR were classified when the weight of the fetus was below the 10th centiles with disturbed placental function and abnormal ultrasonographic examination. The diagnosis was confirmed by the infant's weight at birth. The maternal serum eNOS, NOSTRIN and ADMA concentrations were determined using a sandwich enzyme-linked immunosorbent assays., Results: There were no statistically significant differences in the eNOS and NOSTRIN levels between studied groups of women. Increased levels of ADMA in both preeclamptic groups and in women with pregnancies complicated by isolated IUGR were observed., Conclusions: Our results allow the conclusion that impaired NO bioavailability in pregnancies complicated by severe preeclampsia and/or IUGR result not from a reduced level or activity of eNOS or from its disturbed intracellular transport, but from increased ADMA levels, an endogenous inhibitor of the enzyme eNOS.

Advanced chronic kidney disease (CKD) leads to complications such as anemia, electrolyte abnormalities, bone and mineral disorder, and malnutrition-inflammation-atherosclerosis (MIA) syndrome, that result in high cardiovascu- lar mortality. One of the biomarkers associated with inflammation and cardiovascular events is pregnancy-associated plasma protein A (PAPP-A). The aim of the study was to measure serum PAPP-A in hemodialyzed CKD patients, and to investigate its correlations with the laboratory markers of the complications. We enrolled 78 consecutive stable adult CKD patients treated with maintenance hemodialysis for median period of 60 months. PAPP-A concentrations were measured with by electrochemiluminescence immunoassay. Average serum PAPP-A in hemodialyzed patients was almost two times higher than the upper reference limit. It positively correlated with N-terminal pro-brain natriuretic peptide (NT-proBNP), serum sodium, and the markers of inflammation and malnutrition. In conclusion, serum PAPP-A seems a useful biomarker associated with cardiovascular dysfunction, inflammatory state and malnutrition in hemodialysis patients.

Saponins of marigold (Calendula officinalis), in particular derivatives of 3-O-monoglucuronide of oleanolic acid, are able to reduce infectivity of Heligmosomoides polygyrus in mice. The purpose of this study was to understand the immune activation provoked by third-stage larvae exposed to marigold glucuronides. We also examined the pattern of glycosylation of larval antigens which appeared to be crucial for induction of cytokine production in BALB/c mice; higher concentrations of IL-6, IFN-γ, IL-10 and TNF-α were observed in serum or intestine one week post infection. Three weeks later, in the chronic phase of infection, cells in culture were able to produce IL-6, IFN-γ, TNF-α and IL-17. Restimulation of cells with H. polygyrus antigen resulted in reduced production of IL-6, and TNF-α. The pattern of cytokine production co-existed with reduced expression of terminal glucose, α-linked mannose, N-acetyl-galactosamine, β-galactose, N-acetyl-glucosamine and α-fucose in several protein bands. Galactose, as a new terminal carbohydrate residue appeared in 20-24kDa protein bands. The number of immunogenic epitopes in parasitic antigens was reduced; only three protein bands of 56, 26 and 12kDa were recognized by IgG1. These studies provide a model system to find the glycosylated molecules expressed on nematodes that improve establishment and survival and characterize cytokine production in mice infected with larvae exposed to saponin. Identification of these molecules is the first step in the recognition of key antigenic epitopes able to induce protective or tolerogenic immune responses., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to determine the maternal serum concentrations of eNOS, ADMA, and homocysteine in preeclamptic pregnancies., Material and Methods: The study was carried out on 62 patients with pregnancy complicated by early onset and 53 patients with late onset preeclampsia. The control group consisted of 65 healthy normotensive pregnant patients. The serum eNOS, ADMA and homocysteine concentrations were determined using ELISA assays., Results: Our study revealed elevated levels of homocysteine and ADMA in the serum of women with preeclampsia. The highest levels were observed in patients with early onset preeclampsia, but the differences between both groups of preeclamptic patients with early and late onset of preeclampsia were not statistically significant. Both groups of preeclamptic women had slightly lower levels of maternal serum endothelial nitric oxide synthase than in normotensive pregnant women, but these differences were not statistically significant., Conclusions: The higher levels of homocysteine and ADMA observed in patients with early onset preeclampsia may suggest that higher levels of maternal serum homocysteine and ADMA correlate with the severity, and may determine the earlier clinical onset of the disease. The elevated levels of ADMA and the unchanged levels of eNOS in preeclamptic pregnancies suggest that NO deficiency in this pregnancy disorder results not from a reduced level or activity of eNOS, but from elevated levels of ADMA, an endogenous eNOS inhibitor. The lowering of increased levels of homocysteine and ADMA may be helpful in therapy of vascular disturbances occurring in preeclampsia.

Background: The aim of this study was to show differences of maternal serum sP-selectin levels in pregnancies complicated by intrauterine fetal growth restriction (IUGR) in the course of preeclampsia and to compare the results with normotensive pregnant women with isolated IUGR. These studies were also conducted on preeclamptic pregnancies with appropriate-for-gestational-age weight infants and on the control normotensive pregnant women., Material and Methods: The study was carried out on 55 patients with pregnancy complicated by fetal growth restriction in the course of preeclampsia, 70 normotensive patients with pregnancies complicated by isolated IUGR, 39 preeclamptic patients with appropriate-for-gestational-age weight fetuses and 54 healthy normotensive pregnant patients with normal fetal growth. Maternal serum levels of sP-selectin were determined using the enzyme-linked immunosorbent assay., Results: Levels of sP-selectin were higher in women with pregnancy complicated by preeclampsia with and without IUGR; whereas, in the group of normotensive pregnant women with isolated fetal growth restriction, serum sP-selectin levels tended to be lower than in the control subjects, but this difference was not statistically significant. The mean values were 192.05±70.96 ng/mL in the IUGR group, 293.18±222.92 ng/mL in the PI group, 379.78±353.13 ng/mL in the P group and 227.96±134.04 ng/mL in the healthy controls (p<0.001*)., Conclusions: Our findings may suggest that the elevated level of the soluble P-selectin is associated with preeclampsia, and that it may confirm the presence of platelet and endothelial activation, the presence of the hypercoagulant state and may be due to the systemic inflammatory response in this serious pregnancy disorder.

Objective: The aim of our study was to investigate the association between homocysteine and asymmetric dimethylarginine in preeclamptic women with and without intrauterine growth restriction compared with normal healthy uncomplicated pregnancies and normotensive pregnancies complicated by idiopathic isolated intrauterine fetal growth restriction., Methods: The maternal serum homocysteine and asymmetric dimethylarginine concentrations were determined using a sandwich enzyme-linked immunosorbent assays., Results: A statistically significant positive correlation of maternal serum homocysteine levels with the serum asymmetric dimethylarginine levels was observed in healthy normotensive uncomplicated pregnant women from the control group and in preeclamptic patients with appropriate-for-gestational-age fetuses (R = 0.380079, p-value = 0.002311* and R = 0.455797, p-value = 0.004030* for the control and the P groups, respectively). However, this correlation was not significant in women with pregnancy complicated by intrauterine growth restriction, both isolated and in the course of severe preeclampsia., Conclusion: These findings provide support for the hypothesis that elevated levels of asymmetric dimethylarginine in pregnancy complicated by preeclampsia are associated with elevated homocysteine levels. But our results also demonstrate that in pregnancies complicated by intrauterine growth restriction, this mechanism is important, although not the only one.

Objective: The aim of this study was to determine the maternal serum endoglin concentration in pregnancies with intrauterine growth restriction (IUGR) in the presence or absence of preeclampsia and to compare the results with preeclamptic pregnant women with appropriate-for-gestational-age weight infants and with healthy pregnant controls., Patients and Methods: The study was performed on 52 normotensive pregnant patients with pregnancy complicated by isolated IUGR, 33 patients with preeclampsia complicated by IUGR and 33 preeclamptic patients with appropriate-for-gestational-age weight infants. The control group consisted of 54 healthy normotensive pregnant patients with singleton uncomplicated pregnancies. The maternal serum endoglin concentrations were determined using a sandwich enzyme-linked immunosorbent assay assay., Results: Our study revealed increased levels of endoglin in the serum of women with normotensive pregnancy complicated by isolated IUGR, and in both groups of preeclamptic patients with and without IUGR. The levels of endoglin were the highest in pregnancy complicated by fetal intrauterine growth restriction (IUGR) in the course of preeclampsia. The mean values were 12.2 ± 4.3 ng/ml in the IUGR group, 14.1 ± 3.6 ng/ml in preeclamptic patients with normal intrauterine fetal growth, 15.1 ± 3.2 ng/ml in preeclamptic pregnant women with IUGR and 10.6 ± 3.7 ng/ml in the healthy controls. We also found positive correlations between serum endoglin levels and systolic and diastolic blood pressure and inverse correlations between maternal endoglin and infant birth weight., Conclusions: Our results suggest that increased endoglin concentration may be at least responsible for the pathogenesis of preeclampsia and/or intrauterine fetal growth restriction. It seems that the pathomechanism underlying the development of preeclampsia and isolated IUGR is similar, but that their beginning or intensity may be different in these two pregnancy complications. The positive correlation between endoglin and blood pressure and inverse correlation between endoglin and infant birth weight and additionally higher levels of ENG in patients with pregnancy complicated by HELLP syndrome (hemolysis, increased liver enzymes, low platelet count) or eclampsia suggest that endoglin may be a marker of severity of these pregnancy disorders.

Objective: The aim of this study was to investigate the maternal serum of soluble human leukocyte antigen-G (sHLA-G) levels in pregnant women with an isolated intrauterine growth restricted foetus (IUGR) and in preeclamptic pregnancies with and without IUGR., Patients and Methods: The study was conducted on 31 normotensive patients with pregnancy complicated by IUGR, 17 preeclamptic patients with appropriate-for-gestational-age foetal intrauterine growth, 21 with preeclampsia complicated by IUGR, and 32 healthy pregnant controls. Maternal serum sHLA-G levels were calculated using the enzyme-linked immunosorbent assay., Results: Maternal serum sHLA-G levels tended to be higher in both groups of preeclamptic patients, and were highest in patients with IUGR in the course of severe preeclampsia. Lower serum levels of sHLA-G were observed in the group of normotensive pregnant women with an intrauterine growth restricted foetus, but these differences were not statistically significant. The mean values were 22.759±14.151units/mL in the IUGR group, 25.948±18.888units/mL in preeclamptic patients with normal intrauterine foetal growth, 31.646±27.576units/mL in preeclamptic pregnant women with IUGR, and 24.178±24.828units/mL in the healthy controls., Conclusions: Our findings suggest that the increased levels of sHLA-G in the maternal serum may play a significant role in the pathogenesis of preeclampsia, especially in preeclampsia complicated by intrauterine foetal growth restriction. These associations may offer a better insight into the etiology and pathogenesis of preeclampsia with and without IUGR. It seems that sHLA-G does not play a clinically significant role in the pathogenesis of isolated intrauterine foetal growth restriction in normotensive pregnancies., (Copyright © 2012 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to evaluate maternal asymmetric dimethylarginine (ADMA) levels in pregnancies complicated by isolated fetal intrauterine growth restriction (IUGR), in preeclamptic pregnancies with and without IUGR, and in healthy normotensive pregnant women with proper weight fetuses., Patients and Methods: The study was carried out on 54 normotensive pregnant patients with pregnancy complicated by IUGR, 35 patients with IUGR in the course of preeclampsia, 29 preeclamptic patients with appropriate-for-gestational-age weight infants and 54 healthy normotensive pregnant patients. The ADMA concentrations were evaluated using an ELISA assay., Results: The preeclamptic women and normotensive patients with pregnancy complicated by isolated IUGR revealed higher levels of maternal serum ADMA. The mean values of maternal serum ADMA were 0.5730 ± 0.1769 μmol/l in the P group, 0.5727 ± 0.1756 μmol/l in the PI group, 0.6129 ± 0.1517 μmol/l in the IUGR group, and 0.5017 ± 0.1116 μmol/l in the control group. The levels of ADMA were additionally higher in the patients with HELLP syndrome and in patients with pregnancy complicated by eclampsia., Conclusions: It seems that ADMA is an active agent not only in preeclamptic patients, but also in normotensive pregnant women with isolated fetal IUGR and could be a marker of severity of preeclampsia.

Objective: The aim of present study was to assess the maternal serum levels and clinical significance of interleukin-18 (IL-18) in pregnancies complicated by preeclampsia and/or intrauterine growth restriction (IUGR)., Patients and Methods: The study was carried out on 30 patients with pregnancy complicated by severe preeclampsia (15 patients with IUGR and 15 with appropriate-for-gestational-age weight fetuses), 11 normotensive pregnant patients with pregnancy complicated by isolated IUGR and 32 healthy normotensive women with uncomplicated pregnancies. The interleukin-18 levels were determined using an ELISA assay., Results: Decreased levels of maternal serum IL-18 in preeclamptic patients with and without IUGR were observed. Contrary to the preeclamptic women, no difference was found in the maternal serum levels of IL-18 in normotensive patients with pregnancies complicated by isolated fetal growth restriction. These levels were the same as observed in the healthy controls. The mean values of maternal serum IL-18 were 219.118±180.079pg/mL in the PRE group, 438.170±229.657pg/mL in the group of women with isolated IUGR, and 457.053±528.142pg/mL in the control group. The levels of maternal serum IL-18 were similar in both study preeclamptic subgroups. The mean values of IL-18 were 204.823±188.171pg/mL in the group PI and 233.414±176.995pg/mL in the P group., Conclusions: Our findings suggest that decreased levels of IL-18 in maternal serum play a significant role in etiology and pathogenesis of preeclampsia. But normotensive pregnancies complicated by isolated IUGR are not associated with the altered interleukin 18 levels in maternal serum., (Copyright © 2011 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: The aim of this study was the analysis of the umbilical cord serum sP-selectin levels in pregnancies complicated by severe preeclampsia with and without intrauterine growth restriction and in normotensive pregnancies., Patients and Methods: The study was carried out on 18 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 18 pregnant patients with severe preeclampsia complicated by intrauterine fetal growth restriction (IUGR) (group PI). The control group consisted of 34 patients with singleton uncomplicated pregnancies (group C). Umbilical serum sP-selectin concentrations were estimated using a sandwich ELISA assay according to the manufacturer's instruction (ELISA kit Bender MedSystems Vienna, Austria)., Results: Our study revealed different concentrations of soluble P-selectin in the umbilical cord in our both studied groups of preeclamptic women with and without IUGR. The umbilical cord levels of sP-selectin were decreased in the group with preeclampsia complicated by IUGR and increased in the preeclamptic women with the normal intrauterine fetal growth. The mean values of umbilical sP-selectin were 839.008 ± 625.703 ng/ml in group P, 275.873 ± 174.339 ng/ml in group PI, and 288.719 ± 199.039 ng/ml in the control group, respectively., Conclusions: Higher levels of the umbilical sP-selectin may confirm the presence of platelet and endothelial cell activation and confirm a hypercoagulant state in preeclamptic disorder, especially in preeclampsia without IUGR.

Background: Our study was a continuation of the research on the immunological pathology and changes associated with pregnancy complicated by preeclampsia. The aim of this study was to compare the levels of soluble CD30 in maternal serum in the group of women with preeclamptic pregnancy and in the control group of normotensive healthy pregnant women., Material and Methods: The study was carried out in 50 patients with pregnancies complicated bysevere preeclampsia (Pre group). The control group consisted of 34 healthy normotensive pregnant patients with singleton uncomplicated pregnancies (group K). Maternal serum soluble CD30 concentrations were estimated using a sandwich ELISA assay. There were no statistically significant differences in gravidity, parity, maternal age, body height and BMI in patient profiles between groups. Maternal weight was lower in the control group of patients than in the group of preeclamptic patients. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study group ofpreeclamptic pregnant women than in the control group., Results: The levels of maternal serum soluble CD30 in preeclamptic women did not differ in comparison with healthy controls. The mean values were 21.257+/-10.304 ng/mL in the Pre group compared with 21.806+/-11.076 ng/mL in the control group., Conclusions: Since preeclampsia is not associated with a fall of the maternal soluble CD30 level it can not constitute a measure of improving diagnostic and therapeutic management.

Aim: The comparison of the locus of control in groups of patients hospitalised due to alcohol withdrawal with and without delirium and analysis of psychotic experiences of patients with delirium., Methods: 25 patients with alcohol withdrawal with delirium and 25 without delirium took part in the study. They filled-in the Internal-External (I-E) Locus of Control Scale by Rotter; Multidimensional Health Locus of Control (MHLC) scale; the group with delirium also did the Psychopathological Symptoms Inventory, by Bizoń et al., Results: The mean score in I-E Locus of Control Scale in the group with delirium was more external than in the group without delirium (M = 13.28; SD = 2.762 versus M = 11.64; SD = 2.612; t(48) = -2.157; p = 0.036). Group with delirium had also lower mean score in the dimension of internal control in MHLC, than the group without delirium (M = 24.8; SD = 6.149 versus M = 26.8; SD = 4.648; t(48) = 1.99; p = 0.04). There were no statistically significant differences between the groups in the other subscales. The auditory and visual hallucinations were most common among patients with delirium (84%, 80% respectively, as well as delusions of taking part in not existing events (92%) and persecutory delusions (80%). Psychotic experiences influenced behaviour in nearly 50% of the cases., Conclusions: A more external locus of control may be one of the factors contributing to the development of alcohol delirium. The content of psychotic experiences seems to have impact on the behaviour of many patients with alcohol delirium.

This study investigated the serum concentration of soluble CD30 (sCD30) in pregnant women with isolated fetal intrauterine growth restriction, in pregnancies complicated by preeclampsia with and without accompanying intrauterine growth restriction, and in normotensive healthy pregnant controls. Lower serum concentrations of sCD30 were observed in the group of normotensive pregnant women with a growth-restricted fetus in comparison with the group of healthy pregnant controls, and also in comparison with both preeclamptic groups of pregnant women with and without fetal growth restriction. The concentration of sCD30 in maternal serum from preeclamptic women did not differ in comparison with values from healthy controls or pregnancies complicated by isolated fetal intrauterine growth restriction., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aim: The aim of this study was the comparative analysis of the sP-selectin in pregnancies complicated by severe preeclampsia with intrauterine normal growth and small-for-gestational-age foetus., Patients and Methods: The study was carried out on 14 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 13 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 13 healthy normotensive pregnant patients with singleton uncomplicated pregnancies (group C). Maternal serum soluble P-selectin concentrations were estimated using sandwich ELISA assay according to the manufacturer's instructions., Results: Pregnant women with severe preeclampsia had higher maternal serum sP-selectin levels than the normotensive controls. The sP-selectin levels were highest and statistically significant in preeclamptic patients with appropriate-for-gestational-age weight infants., Conclusions: Our findings indicate an association between the increased levels of sP-selectin and severe preeclampsia. However, further studies are required to validate this association and explore the possibility of clinical importance and causative role of sP-selectin in the pathogenesis of preeclampsia.

We investigated the potential effect of agonists of opioid receptors in the experimental model of Heligmosomoides polygyrus primary infection. BALB/c mice infected with H. polygyrus were treated with naltrexone, a non-specific antagonist of all three types of opioid receptors (mu, delta, kappa) prior to and during infection. The blockade of opioid receptors affected the pattern and level of immune response induced by H. polygyrus in the histotropic phase of infection, which suggests that an opioid receptor-linked mechanism is involved in the immune response of mice during this phase of infection. Down-regulation of the inflammatory response against fourth-stage larvae appeared to be by endogenous opioids influenced cytokines and nitric oxide production by macrophages in the peritoneum and in the gut as well as migration of leukocytes towards the antigens. Down-regulation of these mechanisms by opioid receptor agonists in vivo might account for the decreased resistance to H. polygyrus infection.

Objective: the aim of this study was a comparative analysis of the maternal and umbilical cord Vascular Endothelial Growth Factor A (VEGF-A) and its soluble Receptor type 1 (sVEGF-R1) serum concentrations in pregnancies complicated by preeclampsia with and without intrauterine growth retardation (IUGR) and in normotensive pregnancies., Patients and Methods: the study was carried out on 9 patients with singleton pregnancies complicated by severe preeclampsia with appropriate-for-gestational-age weight infants (group P) and 9 pregnant patients with severe preeclampsia complicated by intrauterine growth retardation (IUGR) (group PI). The control group were 8 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum human VEGF-A and sVEGF-R1 concentrations were assessed using ELISA assay., Results: in our study in both groups of preeclamptic women (P and PI) the concentrations of maternal serum VEGF were lower and the concentrations of soluble VEGF receptor type 1 were higher than in the healthy pregnant women. The umbilical cord concentrations of sVEGF-R1 were increased in the group with preeclampsia complicated by IUGR and decreased in the preeclamptic women with the normal for gestational age foetal growth. On the other hand VEGF concentrations were lower in preeclampsia with IUGR and higher in the preeclamptic women without IUGR., Conclusion: it seems that VEGF may be responsible for the adequate perfusion of fetoplacental unit, normal foetal oxygenation, nutrition and appropriate intrauterine foetal growth. However, it is necessary to conduct further studies on a larger group of patients.

Objectives: The aim of this study was to determine the maternal and umbilical cord serum levels of interleukin-8 (IL-8) in pregnancies complicated by preeclampsia with intrauterine normal growth and intrauterine growth retardation (IUGR), and in normotensive pregnancies., Patients and Methods: The study was carried out on 15 patients with singleton pregnancies complicated by preeclampsia with appropriate for gestational age weight infants and 12 pregnant patients with preeclampsia complicated by IUGR. The control group consisted of 10 healthy normotensive delivering patients with singleton uncomplicated pregnancies. Maternal and umbilical serum IL-8 concentrations were estimated using the ELISA method., Results: There were no statistically significant differences in patient profiles between the groups. Systolic and diastolic blood pressure and mean arterial blood pressure were higher in the study groups in comparison with the control group. Lower birth weight and lower gestational age at birth were observed in the group of patients with preeclampsia complicated by IUGR. Increased maternal and umbilical serum levels of IL-8 were found in both preeclamptic patient groups in comparison with the control group. The umbilical cord blood concentrations of IL-8 in all groups of patients tended to be higher in comparison with the maternal blood., Conclusions: It seems that these higher IL-8 concentrations may be associated with apoptosis, inflammation, neutrophil activation, endothelial cell damage and dysfunction, and increased endothelial permeability. They may also participate in an attempt to compensate for the imbalanced apoptosis and vascular resistance. Our findings suggest a possible significant role of IL-8 in the pathogenesis and sequelae of preeclampsia, especially in preeclamptic pregnancies complicated by IUGR.

Objective: The aim of this study was to determine the maternal and umbilical cord sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth and in preeclamptic pregnancies with intrauterine growth retardation (IUGR)., Patients and Methods: The study was carried out on 8 patients with preeclampsia complicated by intrauterine growth retardation (group PI) and 18 preeclamptic patients with appropriate-for-gestational-age weight infants (group P). The control group consisted of 18 healthy normotensive delivering patients with singleton uncomplicated pregnancies (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated using a sandwich enzyme-linked immunosorbent assay (ELISA)., Results and Conclusions: Pregnant women with severe preeclampsia had higher maternal and umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore significantly higher umbilical levels of sTNF-R1 were observed in the group of patients with preeclampisa complicated by IUGR, compared with preeclamptic patients with appropriate-for-gestational-age weight infants. The umbilical sTNF-R1 levels in preeclamptic groups tended to be higher in comparison with the maternal levels. Our results and those of other reports seem to suggest that TNFalpha and sTNFR1 play a crucial role in pathogenesis and sequelae of preeclampsia with and without intrauterine growth retardation.

Objective: The aim of this study was determination and comparative analysis of the maternal and umbilical cord sCD40L serum levels in pregnancies complicated by pre-eclampsia with and without intrauterine growth retardation (IUGR) and in normotensive pregnancies., Patients and Methods: The study was carried out on 16 patients with singleton pregnancies complicated by severe pre-eclampsia with appropriate-for-gestational-age weight infants and 14 pregnant patients with severe pre-eclampsia complicated by IUGR. The control group consisted of 13 healthy normotensive delivering patients. Five milliliters of blood were taken by venipuncture from each pre-eclamptic patient and from each woman from the control group before active phase of labor and 5 ml of umbilical vein blood were taken immediately after delivery and collected in sterile tubes. Maternal and umbilical serum sCD40L concentrations were estimated using a sandwich ELISA assay., Results and Conclusions: Our results reveal the higher levels of maternal and umbilical sCD40L serum levels in pregnancy complicated by pre-eclampsia with and without IUGR. The mean maternal values were 4.022 +/- 2.399 ng/ml in group P, 3.914 +/- 2.824 ng/ml in group PI and 0.885 +/- 0.064 ng/ml in healthy controls. The mean umbilical values were 2.633 +/- 1.984 ng/ml in group P, 2.703 +/- 1.996 ng/ml in group PI and 1.112 +/- 0.436 ng/ml in the control group. It seems that these higher concentrations of sCD40L protect maternal immune cells bearing CD40 receptor from Fas-mediated apoptosis. Our findings may suggest also enhanced platelet activation in pre-eclamptic patients. It may be one of the factors responsible for the enhanced procoagulatory and proinflammatory properties, and increased cytokine production, and endothelial cell dysfunction in pregnancies complicated by pre-eclampsia., (Copyright 2007 S. Karger AG, Basel.)

Objective: The aim of this study was to determine the maternal and umbilical vein soluble Fas and its ligand (sFasL) serum levels in pregnancies complicated by preeclampsia with intrauterine growth retardation (IUGR)., Patients and Methods: The study was carried out on 11 preeclamptic delivering patients in the third trimester of pregnancy with severe preeclampsia complicated by intrauterine growth retardation. The control group consisted of 12 healthy normotensive delivering patients with singleton uncomplicated pregnancies, without any renal, heart and vascular diseases and with normal laboratory tests. Maternal and umbilical serum soluble Fas and FasL concentrations were estimated using a sandwich ELISA assay., Results and Conclusions: Increased maternal and umbilical vein serum sFas and increased umbilical vein serum sFasL levels were found in the study group in comparison with the control group. In our study in both groups of patient higher maternal sFas values were observed in comparison with the umbilical cord blood. Further studies are necessary to evaluate the role of Fas/FasL pathway in pregnancies complicated by preeclampsia and intrauterine growth retardation.

Objective: The aim of this study was to carry out a comparative analysis of the maternal and umbilical cord TNFalpha serum levels in pregnancies complicated by severe preeclampsia with normal intrauterine fetal growth, in preeclamptic pregnancies with intrauterine growth restriction (IUGR), and in normotensive pregnant patients., Patients and Methods: The study was carried out on eight patients with severe preeclampsia complicated by IUGR and 18 preeclamptic patients with normal intrauterine fetal growth. The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies. Maternal and umbilical serum TNFalpha concentrations were estimated using a sandwich ELISA assay., Results and Conclusions: Pregnant women with severe preeclampsia had significantly higher maternal and umbilical serum TNFalpha levels than those in the normotensive controls. Our findings and other reports indicate that TNFalpha may participate in the pathogenesis and sequelae of preeclampsia with and without IUGR. The results of excessive umbilical serum activity of tumor necrosis factor alpha (TNFalpha) in preeclamptic pregnancy complicated by intrauterine growth restriction (IUGR) may suggest additional changes and dysfunction of the placental-fetal unit and deterioration of placental function, leading to fetal hypotrophia in the course of preeclampsia.

The purpose of this study was to evaluate maternal serum angiotensin I, angiotensin II and aldosterone level, plasma renin activity, angiotensin converting enzyme activity in pregnancies complicated by preeclampsia with and without intrauterine growth retardation. The study was carried out on 26 patients with singleton pregnancy complicated by preeclampsia (group P) and 12 preeeclamptic patients with preeclampsia complicated by intrauterine growth retardation (group PI). The control group consisted of 18 healthy normotensive patients with singleton uncomplicated pregnancies, without any renal, heart and vascular diseases and normal laboratory tests (group K). Decreased angiotensin I level and decreased plasma renin activity in maternal blood in preeclamptic patients were found to be lower in comparison with the control group. Decreased plasma angiotensin II levels in maternal blood in preeclamptic patients were found to be lower in comparison with the control group. Maternal aldosterone levels were lower in both study groups in comparison with the healthy controls. Elevated serum angiotensin-converting enzyme activity in preeclamptic patients without IUGR was found to be higher in comparison with the healthy controls and with the preeclamptic patients with IUGR. Our results and other reports point out the significant role of RAAS activity in the pregnancy complicated by preeclampsia.

This study gives an overview of the health care reform in six Central European countries after the transition from a central planning system to a regulated market economy. We focused on cost containment policies for drugs, especially the requirements for submitting health economic data in the pricing and/or reimbursement processes. The literature review was supplemented with a survey with decision makers at national health authorities in each country. The study covered Croatia, Czech Republic, Hungary, Poland, Slovakia, and Slovenia. All countries had in common that health economic information was used in reimbursement rather than in pricing processes. Differences between the six countries were mainly variations in the relative importance of health economic data and the presence of explicit requirements and guidelines. Published health economic guidelines exist in two countries and one of the six countries applies a mandatory submission system for a selected range of new drugs. In most of the Central European countries it is more typical that authorities issue a brief list of required data for reimbursement submissions that include health economic information among other data. There is a generally widespread expectation towards more systematic and formalized requirements for health economic and outcomes research data appearing within the next 3-5 years in the region.

Objective: To evaluate angiotensin II type 1 receptor (AT1R) in the third trimester placenta from normotensive women and the correlation between placental AT1R immunoreactivity and infant birth weight., Patients and Methods: The study was carried out on 18 healthy normotensive patients with singleton uncomplicated pregnancies. Immunohistochemistry was used to examine the localization of AT1R in the human placenta., Results: Immunohistochemistry using a monoclonal antibody showed that angiotensin II (Ang II) receptor subtype 1 is localized in the decidual cells, syncytiotrophoblast, cytotrophoblast, Hofbauer cells and vascular endothelium. In our study group of patients, we found a significant negative correlation between histological staining in placental tissue and infant birth weight., Conclusion: It seems that the appropriate placental AT1R expression and its normal vascular and endocrine activity plays a very important role in oxygenation and nutrition of the fetus and this ensures proper fetal development and growth.

The aim of this study was to compare the immunoreactivity of angiotensin-II receptor type 1 (AT1R) in the vascular endothelial cells of human placental vessels in normal and preeclamptic pregnancies. Immunohistochemistry was used to examine the localization of AT1R in the vascular endothelium of human placental vessels. In preeclamptic patients without intrauterine growth retardation (IUGR) the mean histological index H score was significantly higher, but significantly decreased in patients with preeclampsia complicated by IUGR in comparison with the control group. Immunolocalization of AT1R in vascular endothelial cells in our study supports the view that angiotensin II may play a role in the regulation of vascular tone and vascular resistance and the actions of other vasoactive factors, vasodilators or vasoconstrictors. However, our results confirmed that AT1R immunoreactivity is elevated in vascular endothelial cells of human placenta from pregnancies complicated by preeclampsia, suggesting a higher activity of the renin-angiotensin-aldosterone system (RAAS) in women with preeclampsia. On the other hand reduced immunoreactivity of AT1R in placental vascular endothelial cells in pregnancy complicated by preeclampsia with IUGR may result from chronic higher RAAS activity and may suggest the decreased ability to compensate and the inability to restore the normal balance between vasodilators and vasoconstrictors. These results may also reflect destructive changes and dysfunction of the vascular endothelium in preeclamptic pregnancy with IUGR., (Copyright 2003 S. Karger AG, Basel)

Objectives: The aim of our study was the assessment of fetal arterial Doppler parameters (umbilical artery and middle cerebral artery) in threatened preterm labor in the course of transdermal nitroglycerin therapy., Materials and Methods: 16 pregnant women in between 27th and 34th week of gestation with symptoms of threatening preterm labor were brought into our study. Patients were treated with transdermal nitroglycerin (5 mg) patches. Maternal blood pressure. Manning's test score and fetal arterial Doppler blood flow were measured., Results: Whereas maternal systolic blood pressure does not vary in the course of therapy, significant decrease in diastolic blood pressure was noted. There was no change in the mean umbilical and middle cerebral artery blood flow in the course of treatment., Conclusions: Nitroglycerin in the form of transdermal therapeutic system releasing nitric oxide doesn't effect fetal artery Doppler parameters. Nitroglycerin may be used as a safe therapeutic agent in treatment of preterm labor.

Objective: The aim of this study was the analysis of the effectiveness and safety of glyceryl trinitrate as a nitric oxide donor for treatment of preterm labour., Patients and Methods: The study was carried out on 50 patients in preterm labour between 28 and 34 weeks of gestation receiving transdermal glyceryl trinitrate (GTN) patches (drug Nitroderm TTS 5 produced by Novartis Pharma AG, Bazylea)., Results: GTN patches appear to be a non-invasive method of suppressing uterine contractions in preterm labour. MAP and systolic blood pressure decreased significantly during the use of nitroglycerin. Diastolic blood pressure and maternal heart rate did not change during the treatment. Neither were significant changes in fetal heart rate or in fetal cardiotocographic recordings detected during or after the treatment., Conclusion: Transdermal glyceryl trinitrate (5 mg/day) may be promising as a safe and effective drug for treatment of preterm labour, especially in patients with higher blood pressure.

Pregnancy in woman with epilepsy arouses several serious medical problems and always belongs to the group of high obstetric risks. The aim of the present clinical study was the evaluation of the antiepileptic treatment efficiency during pregnancy, including risk factor, effects on pregnancy and delivery in epileptic patients. The study group consisted of 84 epileptic pregnant women which delivered between 1992-1998 in Obstetric Departments of University Medical School of Lublin. A randomised group 80 healthy pregnant women constituted the control group. The mean age of the analysed patients was 25 years. 51 epileptic patients were pregnant for the first time, 23 patients for the second time and 10 patients for the third time or more. The mean duration time of the disease was 8.6 years. In our study group: 45 (53.8%) patients experienced primary generalized tonic-clonic seizures and 39 (46.6%) patients experienced partial seizures. 26 patients were treated with monotherapy and the rest with polytherapy methods. The estimation of the seizure frequency during pregnancy in 52 (61.9%) patients did not change, in 13 (15.4%) patients increased. Among obstetric complications: urinary tract infections, hypertonia (EPH-gestosis) were observed. In 4 newborn congenital defects have been noted. Mothers of three of them were treated with Phenydantin (heart lesion, developmental anomaly of fingers). The fourth mother used Convulex (meningoarachnided hernia, hydrocephalus).

Objective: The aim of the study was to analyse the course of pregnancy and labour in women with epilepsy., Material and Methods: The study was carried out on 53 pregnant women with epilepsy who delivered in the Department of Obstetrics and Perinatology of the University School of Medicine in Lublin (group E)., Results: In the group of women with epilepsy there were observed more pregnancy complications. The mean birth weight of infants and the condition of the infant after birth evaluated were lower in the study group E according to Apgar score. The increased risk of congenital malformations and intrauterine foetal growth retardation were observed in children exposed to valproate or carbamazepine in monotherapy or combination of phenobarbital and phenytoin and the combination of phenobarbital, phenytoin and primidone in polytherapy., Conclusion: Women with epilepsy require appropriate pregnancy planning and appropriate neurologic and obstetric care preconceptionally and during pregnancy.

Unlabelled: Preeclampsia is a major complication during human pregnancy. It results from a breakdown in the balance between the vasoconstrictor and vasodilator substances. Angiotensin II is a potent vasoconstrictor, which participates in the regulation of blood pressure and may be involved in the control of vascular tone., Objective: The purpose of this study was to determine the platelet angiotensin II receptor number and angiotensin II level in pregnancies complicated by preeclampsia. Preeclampsia was defined according to American College of Obstetricians and Gynecologists (ACOG) classification., Patients and Methods: Ligand binding techniques were used for the examination of platelet angiotensin II binding sites in the third trimester pregnant women. The study was carried out in 13 patients with singleton pregnancy complicated by preeclampsia. A control group consisted of 17 healthy normotensive patients with singleton uncomplicated pregnancy and normal laboratory tests. All studied patients were nonsmokers., Results and Conclusions: There were no statistically significant differences in patient profiles between groups including gravidity, parity, maternal age, gestational age and height. Maternal weight, BMI and systolic, diastolic blood pressure and mean arterial blood pressure (MAP) were higher in the study group in comparison with the control group. Our study revealed elevated platelet angiotensin II receptor number and decreased maternal angiotensin II level in singleton pregnancies complicated by preeclampsia. There were no correlations between platelet angiotensin II receptor number and plasma angiotensin II level in the studied subjects. Our results are in accord with other published data and point out to the significant role of renin-angiotensin-aldosterone system and angiotensin II receptors in the pathogenesis of preeclampsia.

Background: Amniotomy and oxytocin infusion are the routine methods most frequently applied to induce labor. These methods are not effective when the cervix is unripe. Prostaglandins may accelerate the process of cervical ripening independently of the stimulation of uterine contractions, since they induce the formation of a gap junction (spread of excitation) and release uterine contractions. The purpose of this study is a comparative analysis of the effectiveness and safety of misoprostol and PGE2 in the process of cervical ripening and inducing labor in patients at full term delivery with a live fetus and indications for inducing labor due to an unripe uterine cervix., Material and Methods: The experimental group consisted of 30 patients at 38-41 weeks of gestation who received misoprostol administered into the posterior vaginal fornix (group M). The control group included 26 patients at 39-42 weeks of gestation in whom labor was induced using natural prostaglandin E(2) (group P)., Results: There were no statistically significant differences in maternal age, body weight and height, or uterine cervical ripening between the two groups of patients. The average time of gestation was 0.92 weeks shorter in group M. The time from administration of the drug to the onset of regular contraction activity of the uterus and delivery of an infant was shorter in the group of patients receiving misoprostol intravaginally., Conclusions: Our results would seem to indicate that misoprostol is an effective drug that can be used for elective preinduction and induction of labor. However, the application of this drug to induce labor with a live fetus requires special caution and care, as well as continuous cardiotocographic monitoring to assure the safety of both the mother and the infant.

The influence of Heligmosomoides polygyrus on infection with Trichinella spiralis was studied in BALB/c mice. Mice coinfected with T. spiralis and previously given H. polygyrus harboured both nematode species till day 34. The number of T. spiralis muscle larvae was greater in mice coinfected with H. polygyrus/T. spiralis or T. spiralis/H. polygyrus than after infection with T. spiralis alone. Infection with H. polygyrus did not enhance eosinophil and IL-5 levels induced by T. spiralis. Additionally, the production of IgG1 specific to L1 T. spiralis was inhibited by co-infection. Changes in the levels of IFN-gamma and IgG2a implicated a disturbance in Th2 cell activation during protective response and resulted in the greater number of T. spiralis muscle larvae in coinfected mice.

The group of 100 patients with thyroid cancer operated in Institute of Oncology in Gliwice was described. The risk of anaesthesia, intraoperative complications and the results obtained depend on the preoperative preparation, especially on adequate treatment of endocrine disorders of thyroid, parathyroid and adrenal glands. It is necessary to estimate the presence of multiendocrine disorders in medullary thyroid carcinoma, especially of those with pheochromocytoma, because of its high mortality in the non alfa-blockers prepared patients.

The effect of ketotifen on inflammation in the intestine during T. spiralis infection in BALB/c mice was examined. The lack of enteropathy in treated mice was accompanied to affected the size of worms and the number of worms, but did not prevent the retardation of nematodes in the intestine. Fecundity of females in vitro and the number of muscle larvae were not statistically changed after treatment. Ketotifen reduced the number of mast cells and IgA plasma cells in the intestine. As inflammatory influx, epithelial damage and IgA response are related to the action of T cells, ketotifen affected T dependent reactions in the gut of T. spiralis infected mice.

Unlabelled: Preterm birth remains a major cause of perinatal morbidity and mortality. The purpose of the study was to examine factors influencing on the survival and early prognosis of very low birth weight premature infants in multiple gestation born at the Department of Obstetrics and Perinatology University School of Medicine in Lublin. Congenital malformations were excluded from the study., Conclusion: In this retrospective analysis the reduction in the incidence of respiratory distress syndrome in multiple gestation was observed. Survival was significantly correlated to prenatal corticoid prophylaxis, Apgar score and lack of the respiratory distress syndrome. The mortality showed an inverse correlation to birth weight and age of gestation.

A retrospective analysis of 400 twin and 14 triplet pregnancies at the Department of Obstetrics and Perinatology, University School of Medicine in Lublin, from January 1, 1989 to June 30, 1999 was undertaken. A number increase of multiply pregnancies was observed--from 124 in the period 1989-1992 to 181 in the period 1996-1999. A percentage increase of cesarean sections was observed--from 52.42% to 77.34% respectively. The most frequent indications for the cesarean sections were non-vertex presentation of the first twin, threatened intrauterine infection and threatened intrauterine asphyxia.

Interleukin-5 (IL-5) production, eosinophilia, and IgA responses of BALB/c mice infected with Trichinella spiralis were measured in the peritoneal cavity and intestinal mucosa. Ketotifen, an anti-allergic compound, was used to control the inflammatory response. IgA responses differed against adult and muscle stages of the parasite and between the intestine and the peritoneal cavity. IL-5 and eosinophil production also differed between the intestine and the peritoneal cavity. The occurrence of parasite-specific IgA antibodies in the peritoneal cavity may reflect the migration of cells from the lamina propria. Following ketotifen treatment there was a reduction in the IL-5, eosinophilic, and IgA responses; these responses affected both the size of worms and the number of worms.

Respiratory distress syndrome (RDS) as a consequence of lung immaturity remains a major cause of perinatal morbidity and mortality. TRH used with glucocorticoids shows synergistic influence on surfactant synthesis and morphological lung maturation in preterm born infants. The purpose of this study was to examine the influence of antenatal TRH + glucocorticoids treatment on survival rate of extremely low birth infants (less than 1000 g). We evaluated 94 premature neonates born between 1993 and 1997 at the Department of Obstetrics and Perinatology of University School of Medicine in Lublin. Better survival rate of extremely low birth infants was observed in the TRH + steroids group then in only steroids one. The ratio of RDS was similar in both groups. Further investigations to determine the safety and efficacy of antenatal TRH therapy are needed.

The fusogenic properties of Rz1, the proline-rich lipoprotein that is the bacteriophage lambda Rz1 gene product, were studied. Light scattering was used to monitor Rz1-induced aggregation of artificial neutral (dipalmitoylphosphatidylcholine/cholesterol) and negatively charged (dipalmitoylphosphatidylcholine/cholesterol/dioleoylphosphatidylserin e) liposomes. Fluorescence assays [the resonance energy transfer between N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine and N-(lissamine rhodamine B sulfonyl)dihexadecanol-sn-glycero-3-phosphoethanolamine lipid fluorescent probes, as well as fluorescent complex formation between terbium ions and dipicolinic acid encapsulated in two liposome populations and calcein fluorescence] were used to monitor Rz1-induced lipid mixing, contents mixing and leakage of neutral and negatively charged liposomes. The results demonstrated that Rz1 caused adhesion of neutral and negatively charged liposomes with concomitant lipid mixing; membrane distortion, leading to the fusion of liposomes and hence their internal content mixing; and local destruction of the membrane accompanied by leakage of the liposome contents. The use of artificial membranes showed that Rz1 induced the fusion of membranes devoid of any proteins. This might mean that the proline stretch of Rz1 allowed interaction with membrane lipids. It is suggested that Rz1-induced liposome fusion was mediated primarily by the generation of local perturbation in the bilayer lipid membrane and to a lesser extent by electrostatic forces.

Unlabelled: Labour induction is frequently indicated in women with an unfavourable cervix. Oxytocin and prostaglandins are the most common drugs used for labour induction. Induction of labour with prostaglandins offers the advantage of promoting both cervical ripening and myometrial contractility. The purpose of the study was to evaluate the safety and efficacy intravaginal administration prostaglandin E1 methyl analogue, misoprostol in cervical ripening and induction of labour in term pregnancy and in women with unfavourable cervix (Bishop score < = 4). The approval for this study was given by the Board of Medical Ethics, University Medical School of Lublin in Poland., Materials and Methods: 64 women with indication for termination of pregnancy received either misoprostol (Cytotec-Searle) vaginally (group M, n = 30) or intravenous drip infusion of oxytocin(group Ox, n = 34). We evaluated profile of the studied women (gravidity, weight, height, maternal age, gestational age), effectiveness and safety of the misoprostol and need for oxytocin administration in group M, start of induction-to-active labour interval (contractions), start of induction-to-vaginal delivery interval, hyperstimulation syndrome, delivery within 24 hours of drug application and caesarean section rate. Before starting labour induction a Bishop score was obtained. Statistical analysis was performed. Baseline and outcome variables were tested with student's t-test and c2 analysis. We needed p < 0.05 for statistical significance., Results: There were no differences in the patient profiles (gravidity, weight, height, maternal age, gestational age) between groups except the score of cervical ripening. The Bishop score before induction was lower in group M. The interval between the initiation of induction to active labour was shorter in the misoprostol group (334.23 +/- 126.35 versus 610.00 +/- 352.14 minutes). The mean time between the initiation of induction to delivery was shorter in group M (707.69 +/- 341.15 +/- versus 1025.77 +/- 369.16 minutes). These differences were statistically significant. 28 (93.33%) patients in the misoprostol group delivered within 24 hours compared with 24 (70.59%) women in the oxytocin group. 8 patients in the misoprostol group and 8 patient in the oxytocin group had caesarean section. Labor induction was successful in 30 (100%) women in the misoprostol group compared with 24 (70.59%) patients in the group Ox., Conclusions: Intravaginal misoprostol is an effective, easy to use and cheap drug for the induction of labour, especially for cervical ripening in women with unfavourable cervix (Bishop score < = 4).

Neutral DNA polymorphisms from an 8-kb segment of the dystrophin gene, previously ascertained in a worldwide sample (n = 250 chromosomes), were used to characterize the population ancestral to the present-day human groups. The ancestral state of each polymorphic site was determined by comparing human variants with their orthologous sites in the great apes. The "age before fixation" of the underlying mutations was estimated from the frequencies of the new alleles and analyzed in the context of these polymorphisms' distribution among 13 populations from Africa, Europe, Asia, New Guinea, and the Americas (n = 860 chromosomes in total). Seventeen polymorphisms older tan 100,000-200,000 years, which contributed approximately 90% to the overall nucleotide diversity, were common to all human groups. Polymorphisms endemic to human groups or continentally restricted were younger than 100,000-200,000 years. Africans (six populations) with 13 such sites stood out from the rest of the world (seven populations), where only 2 population-specific variants were observed. The similarity of the frequencies of the old polymorphisms in Africans and non-Africans suggested a similar profile of genetic variability in the population before the modern human's divergence. This ancestral population was characterized by an effective size of about 10,000 as estimated from the nucleotide diversity; this size may describe the number of breeding individuals over a long time during the Middle Pleistocene or reflect a speciation bottleneck from an initially larger population at the end of this period.

We studied two systems of multilocus markers revealed by PCR using primers directing amplification between Alu repeats in a tail-to-tail orientation. Genomic polymorphisms were detected as the presence or absence of the electrophoretic bands representing DNA fragments of a given length. A total of 104 such fragments segregating as Mendelian markers in a panel of eight CEPH families were analyzed by two-point linkage analysis. Fifty-one of these fragments were localized with respect to CEPH markers; they represented 33 loci, 7 of which were multiallelic. Locus-specific oligonucleotides were developed and used as hybridization probes to identify the mapped loci within a complex pattern of inter-Alu PCR products. A great proportion of inter-Alu PCR polymorphisms represented length variants within amplified DNA segments, while others were presumably due to mutations within the priming sites. To describe the expected number of informative loci per typing experiment we introduced a parameter called overall informativity (OI), which provides a single measure of the multiplex ratio and the informativity of markers contributing to a multilocus system (OI of a single locus is equivalent to its heterozygosity and cannot exceed 0.5 for a biallelic codominant marker). High OI values (5.8 and 11.5) of the two presented systems of inter-Alu PCR markers of random chromosomal distribution render them suitable for mapping genomic rearrangements such as genomic deletions in tumoral tissues. This was illustrated by the detection of loss of heterozygosity in the 9q22-qter region in sporadic colon cancer.

Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be approximately 12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbrück model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population.