Outcome of elderly patients with classical Hodgkin's lymphoma.

INTRODUCTION: The optimal management of elderly patients (pts) with Hodgkin's lymphoma is not yet defined. The aims of the present study were: 1) to evaluate clinical and laboratory characteristics of elderly pts; 2) to indentify risk factors for unfavorable outcome. PATIENTS AND METHODS: The outcome of 182 pts ≥ 60 years (y) was retrospectively analyzed (median age, 67y). Mixed cellularity histology was diagnosed in 49.5 %, advanced stage of disease was in 68.7 % pts, CIRS > 3 in 35.7 %, ECOG PS ≥ 2 in 22.9 % (60-69y) of pts. Chemotherapy (CMT) alone was used in 69.2 % and combination of CMT and radiotherapy in 26.9 % of pts. Anthracycline-based CMT received 83.5 % of pts. The median follow-up was 4.5y. RESULTS: The overall response/complete remission rate was 85.6/70.7 %. The median progression free survival (PFS) and overall survival (OS) were 10y and 11.3y, respectively. Estimated 5-y PFS and 5-y OS were 65.7 % (in contrast to 98.2 % in pts < 60y; p < 0.001) and 70.5 % (99.4 % in pts < 60y; p < 0.001). Overall 70 (38.5 %) elderly pts died. The independent risk factors for a shorter OS included CIRS > 3, lymphopenia < 8 % and anthracycline-free CMT, for a shorter PFS anthracycline-free CMT and lymphopenia < 8 %. CONCLUSION: CIRS > 3, lymphopenia < 8 % and anthracycline-free chemotherapy appear to be significant for unfavorable outcome.

[The efficacy and safety of moxonidine in patients with metabolic syndrome (the O.B.E.Z.I.T.A. trial)]. / Ucinnost a bezpecnost podávání moxonidinu u pacientu s metabolickým syndromem (klinické hodnocení O.B.E.Z.I.T.A.).

INTRODUCTION: Treatment with agents neutral to lipid metabolism but with a positive effect on glucose metabolism might significantly improve the long-term prognosis of patients with metabolic syndrome and hypertension. The aim of our non-interventional observational clinical study was to evaluate the safety of treatment with moxonidine and to assess changes to the metabolic syndrome-related laboratory parameters. MATERIALS AND METHODS: A total of 748 patients over 18 years of age (22-87; mean 59; median 60) were included in a 6-month evaluation (two 3-monthly study visits). There were slightly more female patients (n = 401, 54%) with metabolic syndrome (> or = 3 NCE ATP III risk factors) and poorly controlled hypertension. A standardized data collection form was used, blood pressure measurement was standardized as per the guidelines and laboratory samples were assessed in a certified laboratory. The study medication (moxonidine, Cynt) was prescribed to patients with newly diagnosed hypertension and/or patients with hypertension poorly controlled at an initial visit. RESULTS: The majority of patients (98.8%) completed the study. No adverse effects were reported during the study. Moxonidine was mostly prescribed as an add-on treatment to other antihypertensives (81.1% patients) due to the lack of efficacy of the present antihypertensive treatment. The most frequent dose was 0.4 mg/day as monotherapy (44.9% of patients) as well as add on treatment (59.8% of patients). A change to the treatment was performed in 142 (19.2%) of patients during the follow up visit and in 57 (7.7%) of patients during the last study visit. All parameters (blood pressure, body weight, waist circumference, total cholesterol, LDL- and HDL-cholesterol, triglycerides, glycaemia and pulse) have changed highly significantly (p < 0.001). CONCLUSION: Over the 6-month follow up, a highly significant change was observed to all monitored parameters. An addition of monoxidine (Cynt) to an existing treatment resulted not only in a reduction to blood pressure but also in highly significant changes to metabolic parameters without any significant modifications of the treatment. Treatment with monoxidine can be considered as metabolically neutral with an added value of positive effect on metabolic parameters. This is in line with the results of other studies.

[Combination therapy of hypertension in general clinical practice. The results of the KOHYBA study]. / Kombinainí Iécba hypertenze v bezné klinické praxi. Výsledky studie KOHYBA.

INTRODUCTION: The aim of hypertension treatment is to achieve blood pressure target values; in the majority of patients this is achieved with combination therapy. ACE inhibitors and imidazoline receptor agonists have neutral effect on lipid metabolism and positive effect on glucose metabolism. They thus may significantly improve long-term prognosis of patients with hypertension and metabolic syndrome or hypertension and diabetes mellitus. The aim of our research was to evaluate physicians' approach to hypertension treatment and to ascertain the proportion of patients in general clinical practice who require combination treatment to control their hypertension. The study also aimed to assess the knowledge of the type and frequency of adverse events associated with the administered agents. MATERIALS AND METHODOLOGY: The 12-week evaluation (two 6-week visits) included 993 patients with mild to moderate hypertension above 18 years of age (20-92; mean 57; median 56) with proportional distribution of men and women (48% and 51%, respectively). Data were collected using a standard instrument and blood pressure measured in a standard manner according to guidelines. Hypertension was newly identified in 609 patients (61%), insufficiently controlled hypertension in 363 patients (37%) and data on hypertension were missing in 21 patients (2%). The initial therapy was imidapril (Tanatril) 10 mg. On the first follow up visit, it was on the physician's discretion to increase the dose (increase--imidapril 20 mg) or to prescribe a combination of lower doses [low dose combination--imidapril 10 mg + moxonidin (Cynt) 0.2 or 0.3 mg, respectively]. The second visit, scheduled at 12 weeks post study entry, was attended by 965 patients (97%). RESULTS: Eleven (1.1%) patients discontinued the treatment prematurely. Dry irritant cough, occurring in 4, i.e., only 0.4%, patients was the most frequent cause of treatment discontinuation. Over the 12 weeks oftreatment, systolic blood pressure declined from 154 mm Hg to 132 mm Hg (p < 0.001); diastolic blood pressure declined from 92 mm Hg to 80 mm Hg (p < 0.001). By the second visit, normal blood pressure was achieved by 718 (74%) patients. Overweight and obese patients have profited from the treatment significantly more than patients with BMI < 25. This held true for the reduction of systolic blood pressure (p = 0.022 at the first follow up and p = 0.037 at the second follow up, respectively) as well as the reduction of diastolic blood pressure (p = 0.003 at the first follow up and p = 0.001 at the second follow up, respectively). After the first follow up visit, the majority of patients continued to take 10 mg of imidapril (610; 61%). At the second follow up visit, 808 (84%) patients continued on the study medication, 79% of patients were on imidapril (5, 10 or 20 mg) and 21% on imidapril + moxonidin combination. Imidapril monotherapy (no other antihypertensive) was prescribed to 258 (27%) patients. CONCLUSION: Imidapril is an ACE inhibitor with one ofthe lowest incidences (less than 1% of patients) of dry irritant cough. It thus may become an alternative treatment modality in patients who experienced cough while taking other ACE inhibitors. A significant reduction of blood pressure can be expected in the majority of patients at a dose as low as 10 mg.

[IKARUS Project--incidence of bone events in breast cancer: retrospective analysis of patients in oncological centres in the Czech Republic and Slovakia]. / Projekt IKARUS--zjistení incidence kostních príhod u karcinomu prsu: retrospektivní analýza nemocných dispenzarizovaných v onkologických centrech Ceské a Slovenské republiky.

BACKGROUND: Bone incidents today represent, in terms of frequency and the overall effect on the quality of life of patients with breast cancer, a serious health problem. In a number of clinical studies bisphosphonates have been shown to have a positive impact on reducing the risk of bone events and therefore to be effective in the prevention of bone events. The primary objective of this project was to identify the incidence of bone events in patients with metastatic breast cancer treated in the Czech and Slovak Republics. SUBJECTS: Retrospective, multi-centre, non-interventional, epidemiological and explorative studies to identify the incidence of bone events in the defined group of patients and a description of the practice of prevention and treatment of skeletal events in the years 2000-2005. Enrolled were patients with advanced metastatic breast cancer diagnosed in 2000. METHODS AND RESULTS: Analysis of overall survival and survival to disease progression, analysis of patterns of treatment of bone events and the practice of the use of bisphosphonates in the prevention of bone events in metastatic skeleton affection in the normal conditions of clinical practice, analysis of patient compliance in the treatment with bisphosphonates, analysis of the time interval between the occurrence of bone metastases and the occurrence of bone events and, last but not least, survival analysis of patients in relation to bone events. CONCLUSION: This work has shown that the practice of treatment with bisphosphonates since 2000 and assessed the survival of patients with metastatic breast cancer.

[Experience in data management of the clinical retrospective project in Czech and Slovak oncology centres (IKARUS Project)]. / Zkusenosti s managementem dat retrospektivního klinického projektu v podmínkách ceské a slovenské onkologie (projekt IKARUS).

BACKGROUND: The retrospective part of the IKARUS Project (Incidence of Skeletal Related Events in Breast Cancer) was focused on monitoring the incidence of skeletal related events in patients with metastatic breast cancer treated in the Czech and Slovak Republics.The aim was to describe the experience with data collection management in the conditions of the Czech and Slovak Republics. SUBJECTS AND METHODS: Retrospective collection of data in multi-centre, non-interventional, epidemiological and explorative studies. Female patients diagnosed since 2000 were involved in the project in order to respect the five-year period of monitoring and to describe the treatment of the period. RESULTS: During the initiation phase of the retrospective study each of the 18 Complex Cancer Centres in the Czech Republic (see www.linkos.cz) and 18 chosen oncology centres in the Slovak Republic were addressed. In the end, data were collected from 13 oncology centres in the Czech Republic and 12 oncology centres in the Slovak Republic. The initial plan to enrol 650 patients was not completed; data on 254 patients from the Czech Republic and 125 patients from the Slovak Republic were finally analysed.The effectiveness of retrospective data collection in the conditions of Czech and Slovak oncology corresponded with the possibilities of access to data of formerly diagnosed and treated patients. In searching for retrospective data the present hospital information systems could not be used in most oncology centres.Therefore, the cost of retrospective data collection was estimated and was shown to be relatively high. CONCLUSION: The binding methodical conclusion is that unless a systemic change is made in the functionality of hospital information systems and standardised electronic documentation is introduced, the retrospective collection of clinical data in our conditions will be associated with high costs and a relatively low recovery factor.

Increasing the infliximab dose in rheumatoid arthritis patients: a randomised, double blind study failed to confirm its efficacy.

OBJECTIVE: To evaluate the effect of infliximab dose escalation in incomplete responders in a randomised controlled trial. METHODS: 141 rheumatoid arthritis (RA) patients treated with infliximab for 12 months (3 mg/kg; intervals 0, 2, 6 and then 8 weeks) who responded to the drug (disease activity score in 28 joints (DAS28) decrease >1.2) but who were not in remission (DAS28 >2.6) were enrolled into the study. Patients were randomly assigned into arm A, 3 mg/kg, and arm B, 5 mg/kg infliximab every 8 weeks. Outcome measures included the DAS28, its components and C-reactive protein (CRP). RESULTS: There were no significant differences in changes in the DAS28, its components, or CRP in patients in arms A and B during the 12 months of treatment. All patients showed a DAS28 decrease greater than 0.6 after 28 weeks. Eleven patients interrupted therapy in arm A and 14 in arm B. Infusion reactions and non-serious adverse events were observed in 4.2% and 28.2% of arm A patients and in 7.2% and 47.8% of arm B patients. The frequency of serious adverse events was comparable between arms A and B (16.9% and 15.9%, respectively), and the frequency of serious infections was not significantly greater in the higher dose group (5.8%) than in the lower dose group (5.6%). CONCLUSIONS: In this setting, increasing the infliximab dose from 3 mg/kg to 5 mg/kg in RA patients with residual disease activity did not improve efficacy but moderately increased toxicity. These data indicate that a switch to another biological treatment would be a more appropriate strategy in incomplete responders.

Anti-TNF therapy of ankylosing spondylitis in clinical practice. Results from the Czech national registry ATTRA.

OBJECTIVES: To estimate efficacy, safety and adherence to therapy of ankylosing spondlitis (AS) patients included in the Czech National Registry ATTRA, and to look for predictive factors for therapy discontinuation. METHODS: Patients were included according to the guidelines of the Czech Society for Rheumatology, which involve failure of previous therapy, BASDAI >4, and CRP >10 mg/l. Only patients with anti-TNF administered for the first time were analysed. Adherence to therapy was evaluated using Kaplan-Meier analysis and results were presented as cumulative survival. Comparison with data on patients with rheumatoid arthritis (RA) followed in the same registry was made. RESULTS: 310 of AS patients who had reached at least 1 year as well as those who discontinued the treatment before this time point were analysed. Drug survival was longer in patients with AS than in those with RA: 84% vs. 78% and 72% vs. 49% after 1 and 3 years of treatment. Significant risk factors for treatment discontinuation were female gender (RR 2.22, p=0.001) and CRP (RR 1.33, p=0.025). The proportion of patients with BASDAI <4 during the treatment period was higher in the etanercept group than in the infliximab group (p<0.001). The number of patients fully employed increased in the whole group from 48% to 63% after 1 year of treatment. CONCLUSION: Follow-up of patients with AS in the national registry shows that it is an effective and safe way of treatment with longer adherence to anti-TNF therapy in comparison with RA patients.

Mutation analysis of candidate genes SCN1B, KCND3 and ANK2 in patients with clinical diagnosis of long QT syndrome.

The long QT syndrome (LQTS) is a monogenic disorder characterized by prolongation of the QT interval on electrocardiogram and syncope or sudden death caused by polymorphic ventricular tachycardia (torsades de pointes). In general, mutations in cardiac ion channel genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2) have been identified as a cause for LQTS. About 50-60 % of LQTS patients have an identifiable LQTS causing mutation in one of mentioned genes. In a group of 12 LQTS patients with no identified mutations in these genes we have tested a hypothesis that other candidate genes could be involved in LQTS pathophysiology. SCN1B and KCND3 genes encode ion channel proteins, ANK2 gene encodes cytoskeletal protein interacting with ion channels. To screen coding regions of genes SCN1B, KCND3, and 10 exons of ANK2 following methods were used: PCR, SSCP, and DNA sequencing. Five polymorphisms were found in screened candidate genes, 2 polymorphisms in KCND3 and 3 in SCN1B. None of found polymorphisms has coding effect nor is located close to splice sites or has any similarity to known splicing enhancer motifs. Polymorphism G246T in SCN1B is a novel one. No mutation directly causing LQTS was found. Molecular mechanism of LQTS genesis in these patients remains unclear.

[Extension of QT interval as a consequence of risk factor accumulation--case study]. / Prodlouzení QT intervalu jako dusledek kumulace rizikových faktoru: kazuistika.

BACKGROUND: Many non-cardiovascular drugs have a potential for QT interval prolongation. This phenomenon can be related to occurence of ventricular tachycardia torsades de pointes, syncopi and even sudden death. DESCRIPTION OF THE CASE: A female patient treated with antracycline cytostatics developed a depression of left ventricle ejection fraction. At the same time she was administered 2 common drugs with proarrhythmic potential--terfenadine and itraconazole. In this patient hypokalemia also occured. Combination of the above mentioned risk factors led to QT interval prolongation and frequent ventricular tachycardias torsades de pointes degenerating in ventricular fibrillations with need of repeated defibrillations. Both drugs were withdrawn and dysiontaemia corrected. Then arrhythmias disappeared and QT interval completely normalized. In this patient the congenital long QT syndrome was not proved. DISCUSSION AND CONCLUSIONS: In proarrhythmic effect of non-cardiovascular drugs the following factors play role: predisposition of a particular individual, "repolarization reserve", interindividual differences in drug metabolism. The risk factors are age, sex, dysiontaemia, heart disease and drug interactions. By different choice of medication and attention to risk factors teh life threat to the described patient could have been avoided.

[Mutational analysis of LQT genes in individuals with drug induced QT interval prolongation]. / Mutacní analáza LQT genu u jedincu s polékovým prodlouzením QT intervalu.

BACKGROUND: In a long list of non-cardiovascular drugs a risk of QT interval prolongation and thus an increased risk of malignant arrhythmias has been described. The precise mechanism remains unclear. Many of these drugs are potent blockers of cardiac ion channels. Thus, prolongation of repolarization could be caused by latent ion channel genes mutations which are revealed under stress conditions. GROUP OF PATIENTS AND METHODS: Patients were recruited in screening of antipsychotic drugs with proarrhythmic potential, another sporadic cases were reffered from regional hospitals. In 13 individuals pathologic values of corrected QT interval (> 0.44 s in males, > 0.46 s in females) were observed. Eleven patients gave their consent to mutational analysis of KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 genes (associated with congenital long QT syndrome). RESULTS: At present complete results of mutational analysis are available in 8 patients. In 5 individuals changes in DNA sequence were found which are considered normal variants according to the literature (nucleotide and aminoacid polymorphisms, intronic variants). In 1 male a KCNQ1 gene mutation A590T was identified (yet not reported in literature). CONCLUSION: Mechanisms of drug-induced QT interval prolongation is complex and it cannot be explained simply by ion channel disorders.

Treatment of associated anemia in different hematological disorders with epoetin alpha.

The communication is summarizing results of study aimed to ascertain the efficacy of treatment with epoetin alpha in patients with different hematological disorders and, at the same time to evaluate the impact of this treatment on quality of their lives. Treatment efficacy in separate patients of the monitored population has been evaluated not only according to hemoglobin level increase, but also according to its effect on erythrocyte products consumption needed to control anemic syndrome. Overall 134 patients with different lymphoproliferative disorders were included in the evaluation. Full-extended monitoring, i.e. at least 3-month treatment with epoetin alpha, was passed by 127 (94.8%) patients. Favorable effect of epoetin alpha administration was most often reported in patients with multiple myeloma (85.7%), Waldenstrom s macroglobulinemia (80%) and chronic lymphatic leukemia (76.7%). Conversely the lowest efficacy was reported in the group of patients with myelodysplastic syndrome. Administration of epoetin alpha within treatment of underlying anemia in numerous hematological disorders represents suitable alternative to the substitution therapy via erythrocyte transfusions. Approximately 75% of monitored patients showed improvement of life quality, in some cases irrespective of results of treatment of their underlying disorder.

[Comparison of various methods of correction of QT intervals during exercise in familial long QT interval syndrome]. / Srovnání ruzných metod korekce QT intervalu pri zátezi v rodinách se syndromem dlouhého QT intervalu.

BACKGROUND: Pathologic prolongation of QT interval is related to increased risk of arrhythmias. Changes of this parameter are influenced by many conditions, the most important is heart rate. Several formulas have been proposed for mathematical description of QT interval/heart rate relationship. The aim of this study was comparison of different QT interval correction formulas in families with congenital long QT syndrome (LQTS). METHODS: In 28 members of 6 families with LQTS occurrence bicycle ergometry testings were performed. QT and RR intervals were measured before exercise, at peak exercise and in the 1st and the 6th minute of restitution. For QT interval correction single-parameter formulas by Bazett, Fridericia, Malik and Framingham study were used. In 3 families the results could be correlated with genetically proved diagnosis (KCNQ1 gene mutations in 2 families, HERG-KCNH2 gene mutation in the other). RESULTS: In the described group the genetically established diagnosis of LQTS correlated at best with values obtained with correction by Bazett. All the mutation carriers were correctly identified only by this method. The Fridericia, Malik and Framingham formulas failed to identify 2 patients--mutation carriers (both KCNQ1 and HERG-KCNH2 mutations). DISCUSSION: Because of simplicity the Bazett formula remains the most common method of QT interval correction. Moreover, in our study this formula appeared to be the most sensitive for clinical diagnosis of LQTS.

[Occurrence of bleeding in women using combined hormonal contraceptives (ethinylestradiol 35 micrograms/norgestimate 250 micrograms in relation to regularity of administration and cycle start day]. / Výskyt krvácení u uzivatelek kombinované hormonální antikoncepce (etinylestradiol 35 micrograms/norgestimát 250 micrograms) v závislosti na pravidelnosti a zpusobu zahájení uzívání.

OBJECTIVE: To assess the frequency of irregular intermenstrual bleeding in combined oral contraceptive (ethinylestradiol 35 micrograms/norgestimate 250 micrograms, COC) users and the influence of regularity of pill use on this frequency; to assess the occurrence of withdrawal bleeding during weekends in women using the COC from the first Sunday in the cycle (Sunday start method). DESIGN: Prospective, open, non-comparative, multicenter study in 27 centers. METHODS: The first day of the pill use, occurrence of intermenstrual and withdrawal bleeding and regularity of use were assessed by means of patient's bleeding diary. Body weight, blood pressure and side effects were monitored before the oral contraceptive use and after the third cycle. RESULTS: 358 (94%) of 382 women completed the study. Frequency of intermenstrual bleeding was generally low (6.7%, 5.0% and 5.0% in the first, second and third cycle) and highly influenced by regularity of pill use (2.6%, 0% a 1% in regular users versus 30.2%, 32.1% a 24.2% in irregular users). 28%, 40% and 47% of Sunday start users achieved bleeding-free weekends after the first, second and third cycle. Body weight and blood pressure did not change during the study. CONCLUSION: Frequency of intermenstrual (breakthrough) bleeding during the first three months of COC use is highly influenced by regularity of use. In regular users of monophasic COC containing ethinylestradiol 35 micrograms/norgestimate 250 micrograms the frequency of intermenstrual bleeding is bellow 2.6%. In Sunday start users the proportion of women with bleeding-free weekends (i.e. weekends without the occurrence of withdrawal bleeding) increases to 47% after the third cycle.

Activation or detoxification of mutagenic and carcinogenic compounds in transgenic Drosophila expressing human glutathione S-transferase.

Sensitivity of transgenic Drosophila melanogaster with expression of a human gene encoding the glutathione S-transferase alpha subunit (GSTA1-1) to 1,2:5,6-dibenzanthracene (DBA) and 1,2-dichloroethane (DCE) was investigated in the somatic mutation and recombination test (SMART). We performed the same assay in control transgenic flies expressing the bacterial lacZ gene. Three types of transgenic Drosophila strains carrying GSTA1-1 were used: two transgenic strains homozygous for the second chromosome with a single-copy transgene insertion and one strain with two transgene insertions. Larvae carrying the lacZ gene were significantly more sensitive to genotoxic effects of DBA than those carrying three copies of the GSTA1-1 gene. The larvae with lacZ expression showed significantly lower sensitivity to DCE compared with those expressing GSTA1-1. Finally, a pretreatment with buthionine-sulphoximine (BSO) in experiment with DCE significantly decreased the frequency of mutation events in larvae with three GSTA1-1 copies in comparison with others.

[Prediction of the effect of a triphasic contraceptive agent with norgestimate on acne]. / Predikce vlivu trífázového antikoncepcního prípravku s norgestimátem na akné.

OBJECTIVE: Prediction of complexion changes in users of triphasic oral contraceptive containing norgestimate. DESIGN: Analysis of data from a prospective multicentre open study. SETTING: Department of Obstetrics and Gynaecology, Charles University, Prague. METHODS: Acne severity was evaluated in users of a triphasic norgestimate-containing contraceptive within a six month period. Based on subjective evaluation of acne, three subgroups of patients were selected: A) users where acne improved or disappeared; B) users in whom acne deteriorated, C) users who newly developed acne. Differences between group A and the other groups were established in the proportion or distribution of parameters related to the etiology of acne: age, weight, weight changes during the study, presence of hirsutism, presence of a regular menstrual cycle prior to the start of hormonal contraception use, and smoking. RESULTS: The effect of the pill use on acne was assessed in a total of 3,990 women. Out of 1,201 women with acne before the start of the study, improvement or disappearance of acne during the study was reported by 940 users (subgroup A) (78.27%). In 221 women (18.40%), the extent of acne remained unaltered whereas it increased (subgroup B) in only 30 women (2.50%). Acne newly developed during the study in 49 women (subgroup C), i.e., in 1.2% of the whole group. Users showing deterioration of acne (subgroup B) were found to have hirsutism less frequently. The subgroup even showed a decrease in mean weight during the study. Users with newly developed acne were--compared with subgroup A--significantly older, had a lower weight at the start of the study, and showed a higher frequency of regular menstrual cycles prior to starting hormonal contraception. The differences in the incidence of clinical parameters in the subgroups reached only borderline statistical significance and, hence, are not relevant. CONCLUSION: An extensive multicentric study confirmed the beneficial effect of a triphasic norgestimate-containing contraceptive on complexion. The presence of clinical parameters related to the etiology of acne does not allow to predict the individual response of the skin to hormonal therapy.

[The factor V Leiden mutation in users of hormonal contraceptives]. / Leidenská mutace faktoru V u uzivatelek hormonální antikoncepce.

OBJECTIVE: To assess the frequency of factor V Leiden in oral contraceptive users and to define possible anamnestic data that could predict the presence of factor V Leiden. METHODS: Between 1997 and 1998, 583 users of oral estrogen-progestin contraceptives with no history of thrombotic disease were examined. Factor V Leiden was assessed by PCR after isolating DNA from a peripheral venous blood sample. Among other factors, such things as a family history of thromboembolic disease, myocardial infarction and/or stroke in a first-degree relative were monitored. In 448 users cardiovascular complications were evaluated during six months of oral contraceptive use. The data were analyzed using a MS Excel program. P-values were assessed by pair-tests and chi-square tests. SETTING: 1st Department of Obstetrics and Gynecology of Medical Faculty, Masaryk University, Brno. RESULTS: Factor V Leiden frequency was 6.5% in the study group. There were no differences between carriers and others in age, body weight, body mass index and blood pressure. Carriers had significantly more frequently positive family histories of thromboembolic disease or myocardial infarction or stroke. There were no cardiovascular complications observed in a group of 448 users. The positive family histories of any of the above-mentioned conditions have high specificity (97-99%) and a negative predictive value (0.94) with a low sensitivity (2.6-15.8%) in predicting factor V Leiden presence. CONCLUSION: We found a relatively high incidence of Factor V Leiden among oral contraceptive users without a history of thrombotic disease. Through a positive family history of thromboembolic disease or myocardial infarction or stroke, we can predict a Factor V Leiden presence with high specificity but low sensitivity.

[Liver function tests during administration of triphasic contraceptives containing Norgestimate]. / Testy jaterních funkcí v prubehu uzívání trífázové antikoncepce s norgestimátem.

OBJECTIVE: To evaluate serum levels of liver enzymes and bilirubin before and after six cycles of use of a triphasic oral contraceptive containing 35 micrograms of ethinylestradiol and 180/215/250 micrograms of norgestimate (Pramino, Janssen-Cilag). DESIGN: A prospective, open-label, non-comparative, multicentric phase IV study. SETTING: Department of Obstetrics and Gynaecology, 1st Medical Faculty, Charles University, Prague. METHOD: Before the start and after six cycles of Pramino use, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GMT), and bilirubin were determined in women. As the analyses were performed in different laboratories, the evaluation involved: 1. Subgroups of women examined in laboratories with the same reference range; 2. A group of women examined in laboratories with the upper reference range within the mean +/- SD interval; 3. Percentage variations of the measured values from a concrete upper reference limit. RESULTS: When evaluating subgroups of women from laboratories with the same standards, significant decreases in AST and bilirubin were seen in some subgroups, a rise in GMT in one subgroup; the other changes were non-significant. When assessing the entire group and percentage variations from standard, a mild rise in GMT was again seen; however, the values remain deep within the normal range. Values above the upper reference limit at the start of the study either do not change significantly throughout the study, or they normalize spontaneously. CONCLUSION: No clinically significant changes in liver function tests occurred in users of a triphasic oral contraceptive containing norgestimate along with 35 micrograms EE over a period of six cycles of use. The results, as judged by their dynamics, suggest liver function tests are not a useful tool for routine monitoring a healthy combined oral contraceptive user.

[Clinical study of a triphasic contraceptive preparation (Norgestimate 180/215/250 micrograms + ethinylestradiol 35 micrograms) in a population of Czech women]. / Klinická studie s trífázovým antikoncepcním prípravkem (norgestimát 180/215/250 micrograms + etinylestradiol 35 micrograms) v populaci ceských zen.

OBJECTIVE: To assess the efficacy, acceptability and safety of triphasic oral contraceptive pill containing norgestimate 180/215/250 micrograms and ethinylestradiol 35 micrograms. DESIGN AND SETTING: Prospective, open-label, non-comparative, multicenter study in 409 centers in the Czech Republic. METHODS: Body weight, blood pressure, bleeding pattern, headaches, nausea, breast tenderness, acne, pregnancies and side effects were monitored before the start of the treatment, after three and six cycles of oral contraceptive use. Liver function tests were carried out before and after the treatment. RESULTS: Evaluating 26,432 cycles in 4,720 women the theoretical Pearl index was 0.15. There were no significant changes in body weight (61.45 kg before vs 61.58 kg after the treatment). There were clinically significant changes neither in the blood pressure nor in the liver function tests. Evaluating the bleeding pattern there were similar incidences of irregular bleeding/spotting before the treatment and up to the third treatment cycle (16.15%, resp. 17.86%); then the incidence dropped down (8.41% after the third cycle). Amenorhea was very rare (0.41% resp. 0.35% up to, resp. after the third cycle). Decreasing incidences compared to pretreatment state were observed for headache, breast tenderness and acne. The effect on acne was remarkable (28.3% of women complaining of acne before the treatment vs 6.51% after the six treatment cycles). There were no serious adverse events observed during this study. CONCLUSION: Triphasic oral contraceptive pill containing norgestimate and ethinylestradiol proved in a large multicenter study high both efficacy and acceptability.

[Control of gastrointestinal helminthiasis in pasture-reared lambs]. / Tlumení gastrointestinálních helmintóz pri pastevním odchovu jehnat.

Two sheep herds kept in different geographic conditions with spring lambing by the end of March and April (herd No. 1: 400 ewes, 600 metres above sea level; herd No. 2: 450 ewes, 300 metres above sea level) were examined. The dynamics of gastrointestinal nematode and Moniezia spp. cestode egg counts in samples taken regularly every 4 to 5 weeks was studied during the year 1995 with the intention to verify the system of effective control of these helminth infections under pasture conditions of lamb rearing. In ewes a significant rise in gastrointestinal nematode egg counts was proved during the lambing season, "spring rise phenomenon", and during the summer pasture until autumn months with maximum EPG values reaching 150 (Figs. 1 and 2). In lambs that started grazing at 1 to 4 weeks of age, the excretion steeply rose to maximum EPG values 350 and 290, respectively, after 4 to 5 weeks of grazing (Figs. 1 and 2). In order to control these rising infections, ewes were treated with antihelmintic albendazol by the end of February (herd No. 1) and in March (herd No. 2) and lambs during the first or third decade of July. This anthelmintic treatment significantly lowered egg excretion to EPG values lower than 30 in ewes and 50 or 60, respectively, in lambs. Later, during the summer and autumn months, a mild rise of egg counts was found in lambs. These maxima were liquidated anthelmintis treatment in both herds in late autumn months and it also lowered helminth infections to minimum during winter months (EPG values lower than 50). The excretion of Moniezia spp. eggs had the same dynamics as that gastrointestinal nematodes. Values of lamb infection prevalence reached 21% in herd No. 1 and 29% in herd No. 2. Anthelmintic treatment during July controlled cestode findings in lambs. Albendazol (Vermitan susp. 2.5%), dosed 5 mg/kg of body weight, proved highly effective in the control of gastrointestinal nematodes and Moniezia spp. cestodes.

Use of thiopropyl sepharose for the synthesis of an adsorbent for the affinity chromatography of glutathione S-transferase.

Thiopropyl Sepharose 6B in the 2-thiopyridyl-activated form was used for the reversible immobilisation of reduced glutathione (GSH). The resulting affinity matrix was successfully tested as a sorbent for the partial purification of glutathione S-transferase (GST) from pig kidney. The specific elution of the enzyme was performed with 10 mM GSH in Tris-HCl buffer (pH 7.8), non-specific elution with 20 mM dithiotreitol (DTT) in the same buffer.