Presence of hypogammaglobulinemia - a risk factor of mortality in patients with severe sepsis, septic shock, and SIRS.

In this retrospective study we assessed the frequency of hypogammaglobulinemia in 708 patients with SIRS, severe sepsis and septic shock. We evaluated the relationship between hypogammaglobulinemia IgG, IgM and 28 day mortality. Total of 708 patients and 1,513 samples were analyzed. In the three subgroups we investigated, patients met the criteria of SIRS, severe sepsis and septic shock. IgG hypogammaglobulinemia was demonstrated in 114 patients with severe sepsis (25.2%), 11 septic shock patients (24.4%), and in 29 SIRS patients (13.9%). IgM hypogammaglobulinemia was documented in 55 patients with severe sepsis (12.2%), 6 septic shock patients (13.3%), and in 17 SIRS patients (8.1%). Mortality of patients with severe sepsis and normal IgG levels was significantly lower (111 patients; 32.8%) compared with those with IgG hypogammaglobulinemia (49 patients; 43.0%; p=0.001). Mortality of patients with septic shock and IgG hypogammaglobulinemia (n=5) was significantly higher compared with those with normal IgG levels (45.5% vs. 38.2%; p=0.001). Mortality of patients with severe sepsis and IgM hypogammaglobulinemia did not differ from that of patients with normal IgM levels (37.0 vs. 41.8%). Mortality of patients with septic shock and IgM hypogammaglobulinemia was significantly higher compared with those with normal IgM levels (50% vs. 38.5%; p=0.0001). This study documented relatively high incidence of hypogammaglobulinemia IgG and IgM in patients with severe sepsis, septic shock and SIRS respectively. The presence of IgG hypogammaglobulinemia in patients with severe sepsis is independent factor of mortality.

Pregnancy outcome following use of levodopa, pramipexole, ropinirole, and rotigotine for restless legs syndrome during pregnancy: a case series.

BACKGROUND: Restless legs syndrome (RLS) is related to parity, and its symptoms may worsen during pregnancy. Treatment with levodopa or dopamine agonists is the first-line therapy for RLS; however, there are limited data on treatment in pregnancy. We therefore assessed the safety of levodopa, pramipexole, rotigotine, and ropinirole in pregnancy. METHODS: Prospective documentation of pregnancies exposed to levodopa, pramipexole, rotigotine, and ropinirole between 1998 and 2011 was evaluated as to their outcome (teratogenicity or fetotoxicity) by the Berlin Institute for Clinical Teratology and Drug Risk Assessment in Pregnancy. RESULTS: We were able to complete 59 pregnancy outcomes exposed to RLS pharmacotherapy. For specific treatments, the numbers of exposed pregnancies/live born children/spontaneous abortions/induced abortions/malformations were as follows: levodopa only: 38/29 (one pair of twins)/3/7/3; pramipexole only: 12/9/3/0/0; rotigotine only: 2/2/0/0/0; ropinirole only: 3/2/0/1/0; levodopa combined with pramipexole: 3/3/0/0/0; levodopa combined with ropinirole: 1/1/0/0/0. No major birth defects were found with any RLS treatment, and three infants exposed to levodopa had minor anomalies. CONCLUSIONS: In our small prospective case series, there was no increased risk above baseline for major malformations or other adverse outcomes for levodopa and pramipexole. If necessary, levodopa treatment may be considered as an alternative to cabergoline, for which safety has been well documented in pregnancy.

TREM-1 expression on monocytes is not a parameter specific for infectious etiology of systemic inflammatory response syndrome.

UNLABELLED: Determination of mTREM-1 expression on monocytes has been investigated as a perspective diagnostic method to distinguish infectious from non-infectious etiology of the inflammation. THE AIMS OF OUR STUDY WERE: i) to investigate the expression of TREM-1 on monocytes in septic patients and in those after elective spinal surgery without infection; ii) to assess the dynamics of mTREM-1 expression on monocytes and its association with the outcome in patients with severe sepsis. Fifty two patients with severe sepsis, 20 healthy volunteers, and 20 patients after elective spinal surgery were involved in our study. TREM-1 expression on monocytes was evaluated by flow cytometry. Compared with the group of healthy adults (median 42.0, interquartile range (IQR) 30.3-76 MFI), mTREM-1 expression was increased in the group of septic patients both at entry (median 138.4, IQR 78.4-187.5 MFI) and the last examination (median 136.5, IQR 69.0-170.0 MFI) as well as in patients 24 hours after spinal surgery (median 138.5, IQR 45.3-165.5 MFI). The increase was statistically significant. mTREM-1 expression in patients undergoing spinal surgery and those with severe sepsis did not differ. TREM-1 expression on the monocytes in survivors was higher than in non-survivors (p=0.007). TREM-1 levels in septic non-surviving patients correlated weakly with TNF-α levels (r=0.38; p=0.003) and with HLA-DR/CD14 levels (r=0.38; p=0.003). Increased TREM-1 expression on monocytes is not associated exclusively with the presence of systemic infection.

HVRII of mtDNA in cord blood cells of newborn children and in their saliva 10 years later.

Comparison of hypervariable region II nucleotide sequences of mitochondrial DNA obtained from cord blood cells and saliva cells of the same individual at birth and after ten years revealed a few differences at the so-called mutation hot spots (three transitions and three indels within the C-tract). The personal identity of samples was proved by short tandem repeat profiling. Comparison of individuals living in two regions that differ by air pollution, however, did not reveal statistically significantly increased number of mutations in the population from the region of poorer environmental conditions, although indicating such tendency.

Genetic variability of HVRII mtDNA in cord blood and respiratory morbidity in children.

Genetic polymorphisms were examined using direct sequencing of the hypervariable region II (HVRII) in the D-loop of mtDNA in the cord blood of 355 children living in two areas of the Czech Republic - the industrial district of Teplice and the agricultural district of Prachatice. The incidence of the most frequent nucleotide variants of HVRII, C150T (10.1%), T152C (19.7%), T195C (19.7%) and 309.nC (41.4% for 309.2C and 13.8% for 309.3C), and the respiratory morbidity at the ages of 0-2 years and 2-6 years were investigated, considering many other factors such as locality, gender, ethnicity, heating by coal in household, maternal age, asthma bronchiale, allergic rhinitis, pollinosis, conjunctivitis and maternal tobacco exposure during and after pregnancy. We found that the T195C transversion in HVRII is connected with an increased risk of early childhood (0-2 years) bronchitis (RR 1.38, p=0.034, 95% CI 1.04-1.85) and with increased risk of otitis media in children aged 2-6 years (RR 1.62, p=0.032, 95% CI 1.04-2.53). Another polymorphism, 309.nC, is associated with an increased risk of bronchitis in children aged 2-6 years (RR 1.46, p=0.030, 95% CI 1.04-2.06). The results indicate that genetic polymorphisms in mtDNA may be an important factor not only for various types of cancers and neurodegenerative diseases, but also for respiratory morbidity in children.

[Parental smoking and exposure of pre-school children to tobacco smoke]. / Kourení rodicu a expozice predskolních detí tabákovému kouri.

BACKGROUND: During studies on the health of children aged 3 or 4.5 years in Teplice and Prachatice districts of the Czech Republic, we focused also on the extent of smoking in the families and exposure of children to environmental tobacco smoke. METHODS AND RESULTS: In 1128 questionnaires administered to mothers of children born in 1994-1998, 35.6% of mothers indicated that they smoked and 48.9% of fathers/partners (N = 1075) were smokers. Including other family members, there were 41.6% families without any smoker, 30.1% of families with one smoker and 24% families with two smokers (out of 1061 households). Urine samples of 523 pairs of mothers and children (aged 4.5 years) were assayed for cotinine using a RIA radioimmunoassay. Concentration of cotinine was higher than 500 ng cotinine/mg creatinine (the cut-off value for smoking) in 199 of 523 mothers (38%). Exposure of children to environmental tobacco smoke (cotinine levels over 20ng/mg creatinine) was detected in 48.2% of 523 children. There were more children with cotinine levels over 20 ng in Teplice (59.2% of 287 children) than in Prachatice district (34.7% of 236 children). CONCLUSIONS: Cotinine levels in child's urine were significantly positively associated with maternal cotinine levels as well as with smoking of mother and father, and were lower in children visiting kindergarten.

[Immunological monitoring of sepsis using flow cytometry--quantitation of monocyte HLA-DR expression and granulocyte CD64 expression]. / Imunologické monitorování sepse prutokovou cytometrií--kvantitativní stanovení exprese HLA-DR na monocytech a CD64 na granulocytech.

BACKGROUND: Sepsis is a serious disease with a high case fatality rate. A variety of changes in the host immune responsiveness are observed in the pathogenesis of sepsis, ranging from detrimental hyperinflammation to profound immunoparalysis, i.e. acquired immunodeficiency. The level of monocyte HLA-DR expression reflects the functional status of monocytes as antigen-presenting cells and granulocyte CD64 expression is also indicative of infectious inflammation. MATERIAL AND METHODS: Monocyte HLA-DR expression and granulocyte CD64 expression were measured in 49 septic patients and 30 healthy controls using flow cytometry focused on three parameters: positive cell percentage, mean fluorescence intensity and quantitation of antibodies bound per cell (QuantiBRITE). RESULTS: The significance of both monocyte HLA-DR expression and granulocyte CD64 expression in septic patients was confirmed. Monocyte HLA-DR dramatically decreases in septic patients compared to controls, is one of the prognostic factors and correlates with C-reactive protein. In contrast, granulocyte CD64 sharply rises in patients with sepsis and correlates with mediators of systemic inflammation (procalcitonin - PCT), proinflammatory mediators (interleukin-6 - IL-6, lipopolysaccharide binding protein - LBP) and anti-inflammatory cytokines (interleukin-10 - IL10). CONCLUSION: Quantitative monocyte HLA-DR expression and granulocyte CD64 expression are useful indicators in septic patients when considered along with the panel of other markers, monitored over a period of time and in the context of the clinical course of sepsis.

Cell-cycle alterations underlie cyclophosphamide-induced teratogenesis in the chick embryo.

BACKGROUND: Cyclophosphamide (CP) embryotoxicity was documented in several studies on different experimental models. We investigate quantitatively the relationship between the embryotoxic effect of CP and the disturbance of the cell-cycle using flow cytometry. METHODS: Chick embryos on Days 2-4 were treated with 0.5, 1, 2, 4, 8, and 16 microg doses of pure substance of CP by intraamniotic or subgerminal administration routes. Cell-cycle analysis was carried out in the brain, limb buds, hearts, and facial outgrowths dissected from the embryos 6 hr after administration. Samples of nuclear suspensions were obtained by enzymatic and mechanical disintegration of solid tissues in collagenase-dispase, followed by detergent and RNA-ase mediated cytolysis. Nuclei were stained by ethidium bromide. RESULTS: A dose-dependent increase of S-phase cells followed by decrement of G2M cell compartment was observed. The significant block of S-phase cells, however, was not always associated with malformations. The degree of cell-cycle disturbance was expressed more readily by the ratio G2M/S that demonstrated consistently the threshold character of both teratogenic and lethal effects. CONCLUSION: CP-induced cytotoxicity manifested by dose-dependent disturbance of cell-cycle resulted in an overall depression of proliferation activity clearly associated with the occurrence of malformations and embryonic death. Although a non-significant depression of mitotic activity appeared sufficient to produce malformations on Day 2, remarkably deeper disturbance was needed to interfere with the development of the embryos in more advanced stages. Changes in proliferation rate appear to be a primary and most important event in teratogenesis induced by general toxic agents.

[Comparison of procalcitonin, interleukin-6 and C-reactive protein in the differential diagnosis of patients with sepsis syndrome in intensive care units]. / Srovnání prokalcitoninu, interleukinu-6 a C-reaktivního proteinu v diferenciální diagnostice pacientu JIP se syndromem sepse.

UNLABELLED: One of the most difficult tasks in differential diagnosis of patients with septic syndrome at the Intensive Care Units is to differentiate between infection and non-infection etiology of this syndrome. In the last years, new parameters have played an important role in this area--C-reactive protein, Interleukin-6 and procalcitonin. THE AIM: Of the investigation was to compare these three parameters in differential diagnosis of the septic syndrome. THE COHORT AND METHODS: The authors examined 56 patients (17 women and 39 men, mean age being 43 and 51 years, respectively) hospitalized at the Intensive Care Units who corresponded to the criteria of the syndrome of inflammatory response, sepsis or septic shock. A total of 99 examinations were done. The samples were taken up to 24 hours after the beginning of clinical symptomatology and submitted to the laboratory within four hours. Immediately afterwards the determination of concentrations of all three parameters--C-reactive protein, interlaukin-6 and procalcitonin, were done. The results of the examinations were compared to each other as well as to the diagnosis of sepsis--the confirmed infection etiology. RESULTS: In all the evaluated parameters the authors detected significant differences between the values of entry examination and all measurements between the patients with the syndrome of systemic inflammatory response and septic shock as well as among patients with sepsis and the septic shock. Likewise, the authors confirmed significant differences between concentrations of all three parameters in comparing the patients with sepsis and those with the septic shock. Only in the case of procalcitonin there was a significant difference in concentration between patients with the syndrome of systemic inflammatory response of non-infectious etiology and those with sepsis. The concentration of procalcitonin was the only predictive marker of diagnosis with the correlation coefficient r = 0.7263, r2 = 0.5275, P < 0.00005. CONCLUSION: Calcitonin proved to be the most specific parameter in demonstrating infection etiology in patients with the septic syndrome, its predictive value being higher than that of C-reactive protein and Interleukin-6. Monitoring of calcitonin dynamism provides important information on efficiency of the applied antibiotic treatment. In patients with diagnostic uncertainties as far as the etiology of the septic syndrome is concerned; procalcitonin is the parameter of choice, while it may be supplemented with the examination of C-reactive protein.

Effects of 1,2-dibromoethane on haematopoiesis in the chick embryo.

1. Chick embryo in ovo was used to investigate the effects of 1,2-dibromoethane (DBE) on haematopoiesis at a developmental stage where the primitive erythroid cells divide and differentiate in circulation. 2. Early after DBE treatment on embryonic day 3, annexin V/propidium iodide labelling showed acute cell death of erythroid elements, which was subsequently compensated for by the release of immature cells into the circulation. Simultaneously, the comet assay indicated increased DNA damage in DBE-exposed blood cells when compared with controls. 3. After embryonic day 5, there was no indication for ongoing prominent cell death in the DBE-treated group. However, the DNA damage assessed by the comet assay persisted until embryonic day 10 in the peripheral blood cells, and for even longer in cells from thymus and bursa. 4. The kinetics of DNA fragmentation in both erythroid and lymphoid cells implied genotoxic damage by DBE to the stem cells of the definitive elements and transmission of this damage through the successive cell generations. 5. The early chick embryo provides a suitable alternative to mammalian models for investigation of long-term effects of xenobiotics on haematopoiesis.

Levels of apolipoprotein A-II in cerebrospinal fluid in patients with neuroborreliosis are associated with lipophagocytosis.

Levels of most of the examined proteins in cerebrospinal fluid (CSF) of 107 patients with neuroborreliosis were associated with cytological findings, the status of hematoencephalic barrier as evaluated by Qalb (cerebrospinal fluid to serum quotient) and the intrathecal synthesis of immunoglobulins. Cytological findings consisted of normal cytology, or both oligocytosis and pleocytosis of monocytes or lymphocytes. The lipophagic elements were present in 20% of samples. Concentrations of apolipoproteins A-I and A-II in the CSF were correlated with the concentration of albumin without regard to the CSF cytology. The levels of apolipoprotein B were increased only in samples with lymphocytic pleocytosis and Qalb > 7.4. The presence of lipophages in the CSF was significantly associated with the CSF concentration of apolipoprotein A-II.

[Environmental pollution and childhood morbidity]. / Znecistené ovzdusí a nemocnost detí.

BACKGROUND: A study of morbidity of children aged 0 to 3 years was organized in two districts in the Czech Republic. Comparisons were drawn between children living in district Teplice, known for its high air pollution, and those living in Practice, the district with consistently lower particulate and SO2 exposures. METHODS AND RESULTS: 452 children of the follow up study were born between May 1994 and December 1996. Childhood morbidity during the first three years of life was obtained from their pediatric records. Diagnoses were coded using the International Classification of Diseases--the 10th edition, and categorized into broad groups. Children born in Teplice experienced a significantly higher rate of otitis media (and otalgia), gastrointestinal infections, upper respiratory infections, and pneumonia, but they did not differ in the risk of bronchitis or that of viral infections such as varicella. These findings remained valid after the multiple linear regression models were calculated and adjusted for education, maternal age, maternal smoking, and other smokers in the household, breastfeeding, and attendance at the day care. CONCLUSIONS: Air pollution may alter early childhood susceptibility to infection, but other differences between the districts have to be considered: systematic diagnostic differences for several health outcomes between pediatricians in Teplice and Practice, differences in health-care seeking approach of parents, and some hitherto unidentified factors.

The distribution of major lymphocyte subsets in cord blood is associated with its pH.

OBJECTIVES: To assess in venous cord blood the distribution of major lymphocyte subsets according to pH and medications used during labor. DESIGN AND METHODS: Venous cord blood was sampled immediately after labor from 70 newborns (35 males and 35 females) delivered vaginally. Lymphocytes were immunophenotyped by flow cytometry and pH was measured using the AVL 900 automated blood gas analysis system. Data on birth weight, gestational age at delivery, length of labor, presence of stained amniotic fluid, medications used during labor, maternal risk factors, age and parity were collected. RESULTS: The percentage of T lymphocytes decreased while the percentage of NK lymphocytes increased with decreasing pH over the whole range of pH values. The proportions of T and NK lymphocytes were associated with the administration of neuroplegics, spasmolytics or dihydroergotoxin in the first stage of labor. CONCLUSIONS: Cord blood pH and labor-associated variables should be taken into account to adequately interpret the profile of major lymphocyte subsets as a marker of the effect of different prenatal factors on the immune system of neonates.

Childhood morbidity and air pollution in the Teplice program.

BACKGROUND: A study of morbidity of children aged 0 to 3 years was conducted in two districts in the Czech Republic. Comparisons were made between children living in Teplice district, known for its high air pollution, and children living in Practice, a district with consistently lower particulate and SO2 exposures. METHODS AND RESULTS: The children were selected for the follow up based on deliveries from May 1994 to December 1966. Childhood morbidity during the first three years of life of 452 children was extracted from their pediatric records. Diagnoses were coded using the International Classification of Diseases--10th edition, and categorized into broad groupings. Children born in Teplice experienced a significantly higher rate of otitis media and otalgia, gastrointestinal infections, upper respiratory infections, and pneumonia, but did not differ in their risk for bronchitis or for viral infections such as varicella. These findings remained after multiple linear regression models adjusted for education, maternal age, maternal smoking, and other smokers in the household, breastfeeding, and attendance at day care. CONCLUSIONS: Air pollution may alter early childhood susceptibility to infection, but other differences between the districts must be considered: systematic diagnostic differences for several health outcomes comparing pediatricians in Teplice vs. Practice, differences in health-care seeking behavior by the parents, and inadequate control for confounding.

The effect of dibenzo[a,1]pyrene and benzo[a]pyrene on human diploid lung fibroblasts: the induction of DNA adducts, expression of p53 and p21(WAF1) proteins and cell cycle distribution.

Polycyclic aromatic hydrocarbons (PAHs) present in ambient air are considered as potential human carcinogens, but the detailed mechanism of action is still unknown. Our aim was to study the in vitro effect of exposure to dibenzo[a,l]pyrene (DB[a,l]P), the most potent carcinogenic PAH ever tested, and benzo[a]pyrene (B[a]P) in a normal human diploid lung fibroblast cells (HEL) using multiple endpoints. DNA adduct levels were measured by 32P-postlabelling, the expression of p53 and p21(WAF1) proteins by western blotting and the cell cycle distribution by flow cytometry. For both PAHs, the DNA adduct formation was proportional to the time of exposure and dependent on the stage of cell growth in culture. DNA binding was detectable even at the lowest concentration used (24h exposure, 0.01 microM for both PAHs). The highest DNA adduct levels were observed after 24h of exposure in near-confluent cells (>90% of cells at G0/G1 phase), but DNA damage induced by DB[a,l]P was approximately 8-10 times higher at a concentration one order of magnitude lower as compared with B[a]P (for B[a]P at 1 microM and for DB[a,l]P at 0.1 microM: 237+/-107 and 2360+/-798 adducts/10(8) nucleotides, respectively). The induction of p53 and p21(WAF1) protein occurred subsequent to the induction of DNA adducts. The DNA adduct levels correlated with both p53 (R=0.832, P<0.001 and R=0.859, P<0.001, for DB[a,l]P and B[a]P, respectively) and p21(WAF1) levels (R=0.808, P<0.001 and R=0.797, P=0.001, for DB[a,l]P and B[a]P, respectively), regardless of the PAH exposure and the phase of cell growth. The results showed that a detectable increase of p53 and p21(WAF1) proteins (> or = 1.5-fold as compared with controls) requires a minimal DNA adduct level of approximately 200-250 adducts/10(8) nucleotides for both PAHs tested and suggest that the level of adducts rather than their structure triggers the p53 and p21(WAF1) responses. The cell cycle was altered after 12-16h of treatment, and after 24h of exposure to 0.1 microM DB[a,l]P in growing cells, there was approximately 24% increase in S phase cells accompanied by a decrease in G1 and G2/mitosis (G2/M) cells. Cell treatment with 1.0 microM B[a]P resulted in more subtle alterations. We conclude that DB[a,l]P, and to a lesser degree B[a]P, are able to induce DNA adducts as well as p53 and p21(WAF1) without eliciting G1 or G2/M arrests but rather an S phase delay/arrest. Whether the S phase delay observed in our study is beneficial for the survival of the cells remains to be further established.

[Parameters of cellular immunity in maternal and umbilical cord blood in relation to air pollution. Preliminary results of a pregnancy outcomes study]. / Parametry bunecné imunity v materské a pupecníkové krvi ve vztahu k znecistení ovzdusí. Predbezné výsledky projektu výsledky tehotenství.

BACKGROUND: The study is a part of the project Pregnancy Outcome (Teplice Program) examining effects of polluted environment on the quality of reproduction in Teplice (high polluted) and Prachatice (control) districts. Selected parameters of cell mediated and humoral immunity in maternal and umbilical samples after delivery were assayed. METHODS AND RESULTS: Lymphocytes in 768 samples of maternal venous blood and 739 samples of umbilical blood collected in May 1994-October 1997 were phenotyped using flow cytometry. Medical and personal questionnaires were used to obtain data on clinical risk factors during pregnancy, health and life style of mothers, the course and prolongation of labour and newborn's status. The percentages of T and NK lymphocytes in both umbilical and maternal blood were associated with a number of variables, including the course of labour. After adjustment for the other predictors, the percentage of NK lymphocytes was found significantly higher in Teplice than in Prachatice samples--in both maternal and umbilical blood. CONCLUSIONS: A part of the observed difference between distribution of NK and T lymphocytes can be attributed to living in the polluted district. To see effects of polluted environment, the association of seasonal difference in levels of major pollutants with seasonal changes in lymphocyte phenotype will be analyzed.

Cell-cycle alterations within chick embryonic anlagen after cyclophosphamide treatment.

With the aim of explaining a mechanism underlying the dose-dependent change in prevalence of different malformation types (shift in malformation spectra) in a population of chick embryos treated with general cytotoxic agents, we have investigated the effect of cyclophosphamide (CP) on the cell cycle in different organ rudiments. CP was administered intra-amniotically in doses of 2, 4, 8, and 16 micrograms to chick embryos on day 4. Six hours later, the embryos were removed, and limb buds, facial region, brain, and heart rudiments were dissected and treated for isolation of nuclei. The tissues were dissociated mechanically and enzymatically with collagenase-dispase, and suspensions of nuclei were prepared by a detergent and RNAase-mediated cytolysis. Ethidium bromide added to the solution allowed DNA analysis by flow cytometry, which, within the embryotoxic range of doses (4-16 micrograms), revealed a dose-dependent block of cells in the S phase, followed by a decrease of cell numbers in the G2-M phase. The effect of CP on the cell cycle was associated with the degree of damage to the embryo, and dysmorphogenesis appeared proportionate to the magnitude of mitotic inhibition. The results are consistent with the idea that the dose-dependent shift in malformation spectra is causally associated with the dose-dependent and organ-specific depression of mitotic activity.

[Clinico-teratologic counseling and the Teratology Information Service]. / Klinicko-teratologické konzultace a Teratologické informacní sluzby.

Medical records of 1179 pregnant women counselled at the Department of Medical Genetics Klimentska during the period 1990-1995 because of exposure to medicaments during the preconception period and in the first trimester were analyzed. Women exposed to antimicrobial agents prevailed (48 per cent). Most frequent was treatment with Doxycycline, Co-trimoxazole and Metronidazole. 23 per cent of women were exposed to sex hormones, most frequently to oral contraceptives and norethisterone. The average gestational age at exposure to antimicrobial agents was 21.5 days and 30 days at exposure to sex hormones. Specific features of clinical-teratological counselling and the role of the Czech Teratologic Information Service are described.