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1.
HIV Med ; 25(3): 391-397, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38031396

ABSTRACT

INTRODUCTION: Antiretroviral therapy (ART) is integral to HIV prevention, including averting vertical transmission. The World Health Organization (WHO) recommends ART and breastfeeding for all women living with HIV for at least 12 months post-partum [1, 2]. Much of the data on HIV transmission through breastfeeding comes from low-resource settings, with a paucity of data on breastfeeding-related HIV transmission in women living with HIV in other settings. Women Against Viruses in Europe (WAVE), part of the European AIDS Clinical Society (EACS), aims to improve the standard of care for women living with HIV and sought to gain an understanding of breastfeeding guidelines and practice in women living with HIV across Europe. METHODS: A steering group convened by WAVE developed a survey to collate information on breastfeeding trends, practice, and guideline recommendations for women living with HIV in Europe and to establish interest in becoming involved in a collaborative breastfeeding network. The survey was disseminated to 31 countries in March 2022. RESULTS: In total, 25 eligible responses were received: 23/25 (92%) countries have HIV and pregnancy guidelines; 23/23 (100%) guidelines refer specifically to breastfeeding; 12/23 (52%) recommend against breastfeeding; 11/23 (48%) offer an option if certain criteria are met; 12/25 (48%) reported that the number of women living with HIV who breastfeed is increasing; 24/25 (96%) respondents were interested in joining a network on breastfeeding in women living with HIV. CONCLUSIONS: Recommendations vary, and nearly half of the guidelines recommend against breastfeeding. Many countries report an increase in breastfeeding. WAVE will establish a collaborative network to bridge data gaps, conduct research, and improve support for women living with HIV who choose to breastfeed.


Subject(s)
Breast Feeding , HIV Infections , Pregnancy , Female , Humans , Infant , HIV Infections/drug therapy , HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Postpartum Period , Surveys and Questionnaires
2.
Gynecol Oncol ; 161(2): 553-558, 2021 05.
Article in English | MEDLINE | ID: mdl-33608145

ABSTRACT

OBJECTIVE: To examine risk factors for Type I and Type II endometrial cancer (EC) and to directly compare the influence of risk factors for Type II with Type I tumors. Furthermore, to examine whether risk factors for high-grade Type I and Type II tumors differed from low-grade Type I tumors. METHODS: Women with EC diagnosed during 2000-2016 were identified in the Danish Cancer Registry. A case-control analysis was conducted with 1:15 random population controls matched on age and gender. Using conditional logistic regression, odds ratios and 95% confidence intervals on risk factors for Type I and II tumors were estimated. In case-case analyses, risk factors were evaluated in a direct comparison of cases grouped by tumor type and grade. RESULTS: We identified 6958 women with Type I EC and 1206 women with Type II EC. In the case-control analysis, nulliparity and diabetes were associated with increased risk of both tumor types, whereas hormone replacement therapy only increased the risk of Type I EC. When directly comparing Type I and II tumors, the influence of BMI ≥ 30, current smoking, and parity ≥ 3 was strongest for Type I EC. The associations for the majority of risk factors were similar for Type II and high-grade Type I tumors compared with low-grade Type II tumors. CONCLUSIONS: Risk factors for Type I and II tumors were overlapping suggesting that Type II tumors may be less estrogen-independent than previously anticipated. High-grade Type I tumors seemed to resemble Type II tumors more than low-grade Type I tumors.


Subject(s)
Endometrial Neoplasms/epidemiology , Adult , Aged , Case-Control Studies , Denmark/epidemiology , Female , Hormone Replacement Therapy/statistics & numerical data , Humans , Middle Aged , Parity , Risk Factors , Smoking/epidemiology
5.
Hum Reprod ; 34(6): 1139-1145, 2019 06 04.
Article in English | MEDLINE | ID: mdl-30927428

ABSTRACT

STUDY QUESTION: Is the risk of juvenile idiopathic arthritis (JIA) increased in children conceived after fertility treatment, and is an observed association caused by specific types of fertility treatment or by factors associated with the underlying infertility? SUMMARY ANSWER: The risk of JIA in children conceived after fertility treatment (any and specific types of fertility treatment) was not convincingly affected when compared with children born to fertile women. WHAT IS KNOWN ALREADY: It has been suggested that fertility treatment may affect the development of the immune system and thereby increase the risk of developing autoimmune diseases, including JIA. STUDY DESIGN, SIZE, DURATION: This retrospective population-based cohort study included all live-born children in Denmark between 1 January 1996 and 31 December 2012 (n = 1 084 184). The study population was followed from date of birth until first diagnosis of JIA as registered in the Danish National Patient Registry, date of 16th birthday, date of emigration, date of death or end of follow-up (31 December 2014), whichever occurred first. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study cohort was linked to the Danish Infertility Cohort in order to identify children born to women with fertility problems (n = 174 702) and fertility treatment (n = 89 931). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: During a median follow-up period of 10.3 years, 2237 children were diagnosed with JIA. Children born to women with fertility problems had an increased risk of JIA (HR 1.18, 95% CI 1.05-1.32) compared with children born to fertile women. However, the risk was not increased in children conceived after any fertility treatment (HR 1.11; 95% CI 0.95-1.29), or after specific types of fertility treatment being ART (HR 1.05; 95% CI 0.83-1.33), IVF (HR 1.01; 95% CI 0.73-1.38), ICSI (HR 0.98; 95% CI 0.64-1.50) or any fertility drugs (HR 1.10; 95% CI 0.94-1.28) compared with children born to fertile women. The associations between fertility treatment and JIA were also assessed by using children born to women with fertility problems without fertility treatment in the index pregnancy as a reference group, however, the findings did not change substantially. LIMITATIONS REASONS FOR CAUTION: Despite a large study population, the statistical precision in some subgroup analyses may be affected due to the low number of JIA cases. There may be some misclassification of fertility problems, as some women have undiagnosed fertility problems and are therefore not included in the Danish Infertility Cohort; potentially leading to slight attenuation of the association between fertility problems and JIA. WIDER IMPLICATIONS OF THE FINDINGS: The results are based on national data and our findings can therefore be applied to other similar populations. Our results indicate that fertility treatment per se do not increase the risk of JIA but merely that the increased risk of JIA observed among children born to women with fertility problems may be due to underlying factors related to both infertility and JIA. However, as this is the first large study in this field, further studies are needed to confirm our findings. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by grants from the Jascha Foundation, the Aase and Ejner Danielsens Foundation and The Danish Rheumatism Association. All authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Arthritis, Juvenile/epidemiology , Fertility Agents/adverse effects , Fertilization in Vitro/adverse effects , Infertility, Female/therapy , Maternal Exposure/adverse effects , Adult , Arthritis, Juvenile/immunology , Child , Child, Preschool , Denmark/epidemiology , Drug Prescriptions/statistics & numerical data , Female , Fertilization in Vitro/methods , Fertilization in Vitro/statistics & numerical data , Follow-Up Studies , Humans , Infertility, Female/immunology , Maternal Age , Paternal Age , Registries/statistics & numerical data , Retrospective Studies , Risk Assessment , Risk Factors
7.
Pneumologie ; 71(10): 629-680, 2017 Oct.
Article in German | MEDLINE | ID: mdl-29017219

ABSTRACT

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.


Subject(s)
Antitubercular Agents/therapeutic use , Infectious Disease Medicine , Pediatrics , Societies, Medical , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Adolescent , Austria , Child , Child, Preschool , Cross-Sectional Studies , Female , Germany , Humans , Infant , Infant, Newborn , Male , Switzerland , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/epidemiology , Tuberculosis, Multidrug-Resistant/prevention & control , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/prevention & control
8.
Colloids Surf B Biointerfaces ; 158: 416-422, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28719863

ABSTRACT

The regulatory agencies provide recommendations rather than protocols or standard operation procedures for the hemocompatibility evaluation of novel materials e.g. for cardiovascular applications. Thus, there is a lack of specifications with regard to test setups and procedures. As a consequence, laboratories worldwide perform in vitro assays under substantially different test conditions, so that inter-laboratory and inter-study comparisons are impossible. Here, we report about a prospective, randomized and double-blind multicenter trial which demonstrates that standardization of in vitro test protocols allows a reproducible assessment of platelet adhesion and activation from fresh human platelet rich plasma as possible indicators of the thrombogenicity of cardiovascular implants. Standardization of the reported static in vitro setup resulted in a laboratory independent scoring of the following materials: poly(dimethyl siloxane) (PDMS), poly(ethylene terephthalate) (PET) and poly(tetrafluoro ethylene) (PTFE). The results of this in vitro study provide evidence that inter-laboratory and inter-study comparisons can be achieved for the evaluation of the adhesion and activation of platelets on blood-contacting biomaterials by stringent standardization of test protocols.


Subject(s)
Blood Platelets/drug effects , Polymers/pharmacology , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Double-Blind Method , Humans , Multicenter Studies as Topic , Platelet Activation/drug effects , Platelet Adhesiveness/drug effects , Polyethylene Terephthalates/chemistry , Polymers/chemistry , Prospective Studies
9.
Z Geburtshilfe Neonatol ; 216(2): 73-6, 2012 Apr.
Article in German | MEDLINE | ID: mdl-22517047

ABSTRACT

Protocols recommended in the USA and Germany for the postnatal treatment of congenital toxoplasmosis are mainly based on the National Collaborative Chicago-based Congenital Toxoplasmosis Study that calls for daily administration of pyrimethamine in combination with sulfadiazine for several months, then 3 times a week. The recommended total duration of treatment is 12 months. This scheme necessitates frequent white blood cell counts that often result in the discontinuation of treatment because of severe neutropenia even with the concomitant administration of folinic acid. In contrast, the administration of pyrimethamine with sulfadoxine every 2 weeks for 2 years, as used by a referral centre in Toulouse, France, is associated with less toxicity. The efficacy may even be improved, as judged by the rate of new chorioretinal lesions. In the absence of larger randomised studies the Toulouse protocol appears to have several advantages when a decision has to be made to treat infants with congenital toxoplasmosis.


Subject(s)
Postnatal Care/methods , Pyrimethamine/administration & dosage , Sulfadiazine/administration & dosage , Toxoplasmosis, Congenital/drug therapy , Antiprotozoal Agents/administration & dosage , Dose-Response Relationship, Drug , Female , Germany , Humans , Male , Treatment Outcome , United States
10.
Klin Padiatr ; 224(2): 98-110, 2012 Mar.
Article in German | MEDLINE | ID: mdl-22407471

ABSTRACT

The HIV-infection in adults or children and adolescent differs substantially. Differences include the mode of infection, viral dynamics facing a developing immune system and the clinical course of the infection. In addition to the virological, immunological and epidemiological aspects the psychosocial situation is also very different. The above aspects and the decreased number of antiretroviral substances underline the need for specific guidelines for HIV-therapy in children and adolescents. The German Pediatric Working group AIDS (PAAD) has formulated this guideline in 2011 based on new study results, changes in international recommendations and newly available drugs.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , Adolescent , Anti-HIV Agents/adverse effects , CD4 Lymphocyte Count , Child , Child, Preschool , Double-Blind Method , Drug Resistance, Viral , Drug Therapy, Combination , Evidence-Based Medicine , HIV Infections/diagnosis , HIV Infections/virology , Humans , Infant , Prognosis , Randomized Controlled Trials as Topic , Viral Load , Young Adult
11.
Vet J ; 190(2): e31-e42, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21723757

ABSTRACT

Clinicians and pathologists are sporadically asked by owners whether the taking of tumour biopsies may affect the behaviour of the tumour, including its potential to metastasise. Unfortunately, systematic studies on this subject are unavailable in veterinary medicine, and the aim of this study was to estimate the risk of adverse effects of biopsy taking on tumour progression in animals. A systematic review of veterinary and human case reports and clinical studies as well as experimental animal models of biopsy-induced tumour metastasis was undertaken. There were only two veterinary case reports of needle tract metastases (NTM) following the taking of needle biopsies from urogenital and pulmonary tumours. Seventeen experimental studies found a high incidence of NTM but only a rat osteosarcoma and a hamster squamous carcinoma model showed an increased incidence of distant or regional metastases after incision or excision biopsy. In human medicine, the occurrence of NTM has been reported after the taking of biopsies from mesotheliomas (15%), melanomas (11%) and gall bladder tumours (11%), liver metastases of colon carcinomas (4%) and mammary carcinomas (4%) but an incidence of only <1% for all other tumours. Circulating tumour cells increased immediately after the taking of biopsies from human squamous cell, prostate, breast and hepatocellular carcinomas. Although no increased risk of biopsy-induced distant metastasis has been reported for any type of tumour, this is inconclusive due to a lack of non-biopsied control groups in human studies. Reports of biopsy-induced metastasis in animal tumours indicate that the taking of transcutaneous biopsies from urogenital tumours may be associated with a risk of NTM. However, there is no evidence of a general increase in risk of distant metastases in any tumour type in people or animals. The overall risk therefore appears to be negligible when compared to the valuable information obtained from biopsies in veterinary practice.


Subject(s)
Biopsy/adverse effects , Neoplasm Metastasis , Neoplasms/veterinary , Animals , Biopsy/methods , Biopsy/veterinary , Disease Models, Animal , Humans , Neoplasms/pathology
12.
Int J STD AIDS ; 22(5): 294-5, 2011 May.
Article in English | MEDLINE | ID: mdl-21571982

ABSTRACT

The data on the use of tipranavir and enfuvirtide in pregnancy are very limited. We performed a pharmacokinetic profile in a pregnant woman with multidrug-resistant HIV-1 infection at 37 weeks gestation. Tipranavir levels were in the therapeutic range and the cord blood concentration at delivery was relatively high when compared with other protease inhibitors. No enfuvirtide was detected in the fetal compartment. Tipranavir and enfuvirtide were successfully used in pregnancy, but possible toxicities must be kept in mind.


Subject(s)
Anti-HIV Agents/pharmacokinetics , Fetal Blood/chemistry , HIV Envelope Protein gp41/pharmacokinetics , HIV Infections/drug therapy , Peptide Fragments/pharmacokinetics , Plasma/chemistry , Pregnancy Complications, Infectious/drug therapy , Pyridines/pharmacokinetics , Pyrones/pharmacokinetics , Adult , Anti-HIV Agents/administration & dosage , Enfuvirtide , Female , HIV Envelope Protein gp41/administration & dosage , Humans , Peptide Fragments/administration & dosage , Pregnancy , Pyridines/administration & dosage , Pyrones/administration & dosage , Sulfonamides
13.
Eur J Med Res ; 13(8): 371-8, 2008 Aug 18.
Article in English | MEDLINE | ID: mdl-18952519

ABSTRACT

OBJECTIVE: The Paediatric Working Group AIDS (PAAD) initiated a prospective cohort study in order to investigate disease progression in HIV- infected children and adolescents and the effect of antiretroviral treatment regimes. PATIENTS AND METHODS: Between 1998 and 2003, paediatric centres documented HIV-infected patients under clinical care using a questionnaire for basic data and annual follow up. Main outcome measures were: use of antiretroviral therapy, adverse events, disease progression and change of therapeutic regimes. RESULTS: 174 HIV- infected paediatric patients were followed up in 12 centres in Germany and Austria between 1998 and 2003. Initially 54 (31%) patients had no antiretroviral therapy, 35 (20%) received a two-drug regimen (ART) and 85 patients (49%) a highly active antiretroviral therapy (HAART>or=3 drugs). After an observation period of 5 years, 8 patients (4%) had no therapy, 17 (10%) were on ART and 134 patients on HAART (77%). The number of patients with salvage therapy (>or=4 drugs) increased from 5 (3%) to 15 patients (9%). 72 of 166 treated patients (43%) had no change of their drug regimes, 68 patients (41%) had one change and 26 patients (16%)>or=2 changes. Main reasons for changes were increased viral load (49%), immunologic deterioration (21%) and adverse events (14%). During the follow up period no patient died. According to the CDC classification, disease progression was seen in 48 of 174 patients (28%), of whom 20 had deteriorations of clinical categories (A, B, C) and 28 of immunologic categories. Using Kaplan-Meier curves, the mean time from study onset until change of clinical categories was 61 months for patients on HAART, 26 months for patients on ART and 14 months for patients without ART. CONCLUSION: In paediatric patients with HIV infection, disease progression has declined substantially by introduction of HAART. Superiority of HAART compared with ART was demonstrated. Non-adherence as well as other reasons for treatment failure have to be studied more carefully.


Subject(s)
HIV Infections/diagnosis , HIV Infections/drug therapy , Adolescent , Adult , Anti-Retroviral Agents/pharmacology , Antiretroviral Therapy, Highly Active , Child , Child, Preschool , Cohort Studies , Disease Progression , Female , Germany , HIV Infections/pathology , Humans , Infant , Male , Medication Adherence , United States
14.
HIV Med ; 9(1): 6-13, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18199167

ABSTRACT

OBJECTIVE: The aim of the study was to assess the risk of adverse pregnancy outcomes after antenatal antiretroviral therapy in a well-defined prospective cohort of nontransmitting HIV-infected women. METHODS: Prospective monitoring of 183 mother-child pairs from 13 centres in Germany and Austria, delivering between 1995 and 2001, was carried out. Following German-Austrian guidelines recommending an elective Caesarean section (CS) at 36 weeks, prematurity was defined as <36 weeks' gestation for these analyses. RESULTS: Of 183 mother-child pairs, 42% were exposed to antenatal monotherapy and 17% to dual therapy. Of the 75 women exposed to highly active antiretroviral therapy (HAART), 21 (28%) received protease inhibitor (PI)-based HAART and the remaining 54 received nonnucleoside reverse transcriptase inhibitor-based HAART. In multivariable analysis (176 pregnancies), PI-based HAART exposure during pregnancy was associated with an increased risk of premature delivery [adjusted odds ratio 3.40; 95% confidence interval (CI) 1.13-10.2; P=0.029, compared with monotherapy]. Congenital abnormalities affected 3.3% infants. Perinatally, 18.9% of children (34 of 179) had respiratory problems requiring interventions, which were associated with prematurity but not with type of treatment exposure. From adjusted regression analysis, the mean birth weight z-score for children exposed to HAART with PI (+0.46; 95% CI 0.01-0.92; P=0.047) or dual therapy (+0.43; 95% CI 0.03-0.82; P=0.034) was slightly but significantly higher than that for those exposed to monotherapy; head circumference was appropriate for gestational age and there were no significant differences between treatment groups. CONCLUSIONS: Use of antenatal PI-based HAART initiated before or during pregnancy was associated with a significantly increased risk of premature delivery at <36 weeks' gestation. The overall crude prematurity rate was 34% (63 of 183; 95% CI 28-42).


Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , Congenital Abnormalities/etiology , HIV Infections/drug therapy , Infant, Premature , Obstetric Labor, Premature/chemically induced , Pregnancy Complications, Infectious/drug therapy , Pregnancy Outcome , Adolescent , Adult , Austria , Birth Weight/drug effects , Female , Germany , HIV Infections/transmission , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Pregnancy , Pregnancy Complications, Infectious/virology
15.
AIDS ; 21(8): 947-55, 2007 May 11.
Article in English | MEDLINE | ID: mdl-17457088

ABSTRACT

OBJECTIVE: To describe the long-term efficacy over 5 years of regimens including combinations of abacavir, lamivudine and/or zidovudine in previously untreated children in the PENTA 5 trial. DESIGN: PENTA 5 was a 48-week randomised controlled trial comparing three dual nucleoside reverse transcriptase inhibitor (NRTI) combinations as part of first triple antiretroviral therapy (ART). METHODS: 128 ART-naïve children were randomised to zidovudine\lamivudine (n = 36), zidovudine\abacavir (45) or lamivudine\abacavir (47). Asymptomatic children (n = 55) were also randomised to nelfinavir or placebo; all other children received open-label nelfinavir. Analyses are intent-to-treat and adjusted for minor baseline imbalances and receipt of nelfinavir/placebo. RESULTS: Median follow-up was 5.8 years. By 5 years, 17 (47%), 28 (64%) and 18 (39%) children had changed their randomised NRTIs in the zidovudine\lamivudine, zidovudine\abacavir and lamivudine\abacavir groups respectively, but 18%, 50% and 50% of these changes were either early single drug substitutions for toxicity or switches with viral suppression (HIV-1 RNA < 400 copies/ml; e.g. to simplify regimen delivery). At 5 years, 55%/32% zidovudine\lamivudine, 50%/25% zidovudine\abacavir and 79%/63% lamivudine\abacavir had HIV-1 RNA < 400/< 50 copies/ml respectively (p = 0.03/p = 0.003). Mean increase in height-for-age 0.42, 0.68, 1.05 (p = 0.02); weight-for-age 0.03, 0.13, 0.75 (p = 0.02). Reverse transcriptase resistance mutations emerging on therapy differed between the groups: zidovudine\lamivudine (M41L, D67N, K70R, M184V, L210W, T215Y); zidovudine\abacavir (M41L, D67N, K70R, L210W, T215F/Y, K219Q); lamivudine\abacavir (K65R, L74V, Y115F, M184V). CONCLUSIONS: Five year data demonstrate that lamivudine\abacavir is more effective in terms of HIV-1 RNA suppression and growth changes, with lower rates of switching with detectable HIV-1 RNA than zidovudine\lamivudine or zidovudine\abacavir, and should be preferred as first-line NRTI backbone.


Subject(s)
Dideoxynucleosides/therapeutic use , HIV Infections/drug therapy , HIV-1 , Lamivudine/therapeutic use , Reverse Transcriptase Inhibitors/therapeutic use , Adolescent , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active/methods , CD4 Lymphocyte Count , Child , Child, Preschool , Drug Resistance, Viral , Follow-Up Studies , Growth/drug effects , HIV Infections/immunology , HIV Infections/physiopathology , HIV Infections/virology , HIV-1/isolation & purification , Humans , Infant , RNA, Viral/blood , Treatment Outcome , Viral Load , Zidovudine/therapeutic use
16.
Biomaterials ; 25(21): 5101-13, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15109834

ABSTRACT

Thrombomodulin (TM) serves as the endothelial cell receptor for thrombin and alters its characteristics from pro- to anticoagulant. Additionally, it promotes the formation of activated protein C. We evaluated the conservation of the overall outcome of these functions in recombinant TM linked to artificial surfaces by incubation with human whole blood in vitro. TM was covalently immobilized through poly(ethylene glycol) (PEG) spacers onto thin films of poly(octadecene alt maleic anhydride) covering planar glass substrates. TM binding to the polymer films was achieved after active ester formation at the carboxylic acid terminus of the PEG spacers and thoroughly characterized by HPLC-based amino acid analysis, immunofluorescence and ellipsometry. TM-coated samples were incubated for 3h with freshly drawn whole human blood anticoagulated with heparin (5IU/ml) using in-house developed incubation systems. The substantially reduced activation of blood coagulation (TAT) for TM-coated samples correlates well with the degree of contact activation (bradykinin and FXIIa formation) while no significant effects were observed for the platelet activation (PF4). Further, complement activation (C5a levels), was strongly diminished at the TM-containing surfaces. We conclude that the suggested method for preparation of TM immobilization may serve to prepare model substrates for studies on TM interactions but similarly provides a promising coating strategy for blood contacting medical devices.


Subject(s)
Blood Coagulation/physiology , Coated Materials, Biocompatible/administration & dosage , Coated Materials, Biocompatible/chemistry , Complement Activation/drug effects , Thrombomodulin/administration & dosage , Thrombomodulin/chemistry , Adsorption , Adult , Anticoagulants/chemistry , Anticoagulants/metabolism , Anticoagulants/pharmacology , Blood Coagulation/drug effects , Humans , Materials Testing , Polymers/chemistry , Surface Properties
17.
Biomaterials ; 25(17): 3493-501, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15020123

ABSTRACT

We present a surface coating with anticoagulant characteristics showing significantly reduced coagulation activation. The synthesis of a monomeric conjugate containing a benzamidine moiety was carried out and its inhibitory activity against human thrombin, the key enzyme of the blood coagulation cascade, was determined using a chromogenic assay. Based on that, low-thrombogenic interfaces were prepared by covalent attachment of this low-molecular weight thrombin inhibitor on poly(octadecene-alt-maleic anhydride) copolymer thin films and characterized using ellipsometry, XPS and dynamic contact angle measurements. The in vitro hemocompatibility tests using freshly drawn human whole blood showed, in agreement with the SEM images, that a PO-MA film modified with a benzamidine moiety using a PEG spacer decreased the activation of coagulation, platelets and the complement system. The decreased protein adsorption, in addition to the specific inhibition of thrombin, effectively enhanced the short-term hemocompatibility characteristics.


Subject(s)
Benzamidines/chemistry , Benzamidines/pharmacology , Blood Platelets/cytology , Blood Platelets/physiology , Blood , Maleic Anhydrides/chemistry , Platelet Activation/physiology , Adsorption , Anticoagulants/chemistry , Anticoagulants/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Blood Platelets/drug effects , Cells, Cultured , Humans , Materials Testing , Platelet Activation/genetics , Polymers/chemistry , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/pharmacology , Surface Properties , Thrombin/metabolism
18.
J Biomed Mater Res B Appl Biomater ; 66(1): 379-90, 2003 Jul 15.
Article in English | MEDLINE | ID: mdl-12808598

ABSTRACT

Success in the development of hemocompatible biomaterials depends on adequate equipment and procedures for standardized analysis of blood-materials interactions in vitro. In view of the limited standard of knowledge on that important aspect, two novel incubation systems were designed, built, and evaluated for the in vitro assessment of the hemocompatibility of planar solid surfaces: A screening setup was introduced for the comparison of up to 12 different samples. A perfusion setup was developed to model the directed blood flow in the vascular system during incubation by a recirculation circuit, allowing the variation of the wall shear rate at the sample surface. The incubation procedures utilized freshly drawn, heparinized whole human blood. Hemocompatibility in terms of selected aspects of coagulation, thrombogenicity, and immune responses was quantified through plasma levels of characteristic molecules (immunoassays), cell counting, and analysis of adherent cells and fibrin formation (scanning electron microscopy), respectively. Prevention of blood-air contact and mechanical stress, constant temperature and blood pH during incubation, and the suitable choice of reference materials were found to be crucial for reliable testing. Considering those requirements, screening and perfusion system both provided sensitive discrimination between a given set of planar solid surfaces. In conclusion, the suggested methods for an in vitro hemocompatibility assessment permit versatile, sensitive, and efficient analysis of important blood-material interactions despite the unavoidable variability of blood characteristics in different experiments.


Subject(s)
Biocompatible Materials , Blood , Materials Testing/instrumentation , Complement Activation , Equipment Design , Glass , Hemolysis , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Materials Testing/methods , Microscopy, Electron, Scanning , Platelet Activation , Polytetrafluoroethylene , Surface Properties , Thrombin/biosynthesis
19.
Br J Haematol ; 113(3): 737-45, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11380465

ABSTRACT

Haematological, immunophenotypic and cytogenetic characteristics were analysed in 241 patients with acute myeloid leukaemia (AML) M0, including 58 children. Children < 3 years and adults between 60 and 70 years of age were most frequently affected. Immunophenotyping showed a heterogeneous phenotype. Anti-myeloperoxidase was positive in about half of the patients. Cytogenetic data were available from 129 (54%) patients. A normal karyotype was found in only 24%. Most of the abnormalities were unbalanced and the chromosomes 5, 7, 8 and 11 were the most frequently affected. Survival data were available from 152 treated patients (63%). The median overall survival for all patients was 10 months, 20 months for children (n = 36), 10 months for the young adult group (n = 50) and 7 months for the elderly patients (n = 66) (P = 0.09). Karyotype was not a prognostic factor influencing survival. AML M0 shows the immunological characteristics of early progenitor cells, but the expression of the different markers and cytogenetic abnormalities is heterogeneous. The prognosis is poor compared with other de novo AML and similar to that of AML with multilineage dysplasia or AML following myelodysplastic syndromes.


Subject(s)
Leukemia, Myeloid/classification , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Antigens, CD/blood , Biomarkers/blood , Chi-Square Distribution , Child , Child, Preschool , Chromosome Aberrations , Chromosome Disorders , Female , Flow Cytometry , Humans , Infant , Leukemia, Myeloid/genetics , Leukemia, Myeloid/immunology , Leukocyte Count , Liver/immunology , Lymph Nodes/immunology , Male , Middle Aged , Platelet Count , Spleen/immunology , Statistics, Nonparametric , Survival Rate
20.
Haematologica ; 86(2): 154-61, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11224484

ABSTRACT

BACKGROUND AND OBJECTIVES: AC133 is a novel monoclonal antibody (Moab) reacting with a population of immature/primitive or granulo-monocytic committed CD34+ve cells. Up to now, only few studies with small numbers of cases have examined AC133 (recently designated CD133) expression in acute leukemia. To determine the value of this Moab for acute leukemia immunophenotyping, we investigated a large series of leukemic cell samples for their reactivity with Moab AC133. DESIGN AND METHODS. A total of 298 cell samples from patients with de novo acute myeloid leukemia (AML) (n=142), acute lymphoblastic leukemia (ALL) (n=119), CD34+ve biphenotypic acute leukemia (n=13), and CD34+ve CML blast crisis (=BC; 21 myeloid BC/3 lymphoid BC) were investigated by flow cytometry for Moab AC133 reactivity.CD133 expression was compared with CD90(Thy-1) expression, another CD34-associated antigen. RESULTS: Fifteen (5%) samples expressed CD90, whereas 114 (38%) samples were positive for Moab AC133 (20% cut-off level). No significant differences in CD133 and CD90 expression levels between AML and ALL were observed. In AML, but not ALL, CD133 was more often expressed in CD34+ve cases than in CD34-ve ones (p<0.00001). However, CD133 expression was not restricted to CD34+ve leukemic cells in individual cell samples. All 8 pro-B-ALL cell samples with 11q23-anomalies and MLL (mixed lineage leukemia) gene translocations were positive for CD133, whereas only 2 of 9 pro-B-ALL without MLL gene translocations expressed CD133 (p<0.002). In contrast, none of the 5 AML cell samples with a t(9;11) and MLL gene translocation reacted with Moab AC133. CD34+ve CML cells in myeloid BC were less often positive for CD133 than CD34+ve de novo AML cells (p<0.0001). INTERPRETATION AND CONCLUSIONS: CD133 and CD90 expression analysis is not helpful for lineage determination in acute leukemia immunophenotyping. However, MoabAC133 may be an informative marker for the detection and further characterization of immature AML cells, as well as pro-B-ALL cells with MLL gene translocations, by flow cytometry.


Subject(s)
Glycoproteins/metabolism , Leukemia/blood , Peptides/metabolism , Thy-1 Antigens/metabolism , AC133 Antigen , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal , Antigens, CD , Antigens, CD34/metabolism , Cell Lineage/immunology , Child , Child, Preschool , Glycoproteins/immunology , Hematopoietic Stem Cells/immunology , Humans , Immunophenotyping , Infant , Leukemia/immunology , Middle Aged , Peptides/immunology
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