Biomedical subjects

Martin Langer

Publications and source records attributed to Martin Langer.

At least 19 recordsLinked to original sources

PubMed2006

MRI of fetal acquired brain lesions.

Acquired fetal brain damage is suspected in cases of destruction of previously normally formed tissue, the primary cause of which is hypoxia. Fetal brain damage may occur as a consequence of acute or chronic maternal diseases, with acute diseases causing impairment of oxygen delivery to the fetal brain, and chronic diseases interfering with normal, placental development. Infections, metabolic diseases, feto-fetal transfusion syndrome, toxic agents, mechanical traumatic events, iatrogenic accidents, and space-occupying lesions may also qualify as pathologic conditions that initiate intrauterine brain damage. MR manifestations of acute fetal brain injury (such as hemorrhage or acute ischemic lesions) can easily be recognized, as they are hardly different from postnatal lesions. The availability of diffusion-weighted sequences enhances the sensitivity in recognizing acute ischemic lesions. Recent hemorrhages are usually readily depicted on T2 (*) sequences, where they display hypointense signals. Chronic fetal brain injury may be characterized by nonspecific changes that must be attributable to the presence of an acquired cerebral pathology. The workup in suspected acquired fetal brain injury also includes the assessment of extra-CNS organs that may be affected by an underlying pathology. Finally, the placenta, as the organ that mediates oxygen delivery from the maternal circulation to the fetus, must be examined on MR images.

Brain Injuries↗

PubMed2006

Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study.

AIMS: To evaluate the efficacy and safety of methadone versus buprenorphine treatment in pregnant opioid-dependent women. DESIGN: Randomized, double-dummy, double-blind, flexible-dosing comparison study. SETTING: Addiction Clinic at the Medical University of Vienna, Austria. PARTICIPANTS: Eighteen women were assigned randomly to receive either methadone (n = 9) or buprenorphine (n = 9) during weeks 24-29 of pregnancy. After dropouts, data were available from 14 cases (six in the methadone and eight in the buprenorphine group). INTERVENTION: Sublingual buprenorphine tablets (8-24 mg/day) or oral methadone solution (40-100 mg/day), with matched placebos. MEASUREMENTS: Mothers: retention in treatment, urine toxicology and nicotine use. Neonates: Routine birth data, neonatal abstinence syndrome (NAS) in severity and duration. FINDINGS: There was somewhat greater retention in the buprenorphine group but significantly lowered use of additional opioids in the methadone group (P = 0.047).Neonates: There was earlier onset of NAS in neonates born to the methadone (mean 60 hours) than to the buprenorphine groups (mean 72 hours after last medication); 43% did not require NAS-treatment with short treatment duration in both groups (mean 5 days). CONCLUSION: This preliminary study had limited power to detect differences but the trends observed suggest this kind of research is practicable and that further studies are warranted.

Buprenorphine↗

PubMed2005

Adaptation and performance of an immuno-PCR assay for the quantification of Aviscumine in patient plasma samples.

An immuno-polymerase chain reaction (IPCR) assay is used to evaluate the kinetic behaviour of the novel anti-cancer drug Aviscumine in plasma samples taken from 41 patients during a 3-year clinical trial. The ultrasensitive IPCR assay employed the amplification of a detection-antibody linked marker-DNA and an internal competitor DNA for standardization, thus enabling the detection of the antigen in concentrations far below the detection limit of conventional enzyme-linked immuno-sorbent assay (ELISA). The quantification of Aviscumine was carried out using external calibration curves obtained from individual patient plasma samples, collected previous to the administration of Aviscumine, which were spiked with known amounts of the reference substance Aviscumine. Additional controls were measured containing standardized human serum spiked with Aviscumine to assure the continuous general reproducibility of the assay as well as to estimate differences between individual patients. Average recovery was found to be 95+/-19% and the average deviation in precision of the assay was determined to be 9+/-5%. Data for the quantification of Aviscumine were obtained from all patient samples investigated with the exception of a single patient. The collected data provided the basis for the valid routine quantification of patient samples for the calculation of the pharmacokinetic behaviour of Aviscumine in patient plasma.

Algorithms↗

PubMed2005

Microsurgical training curriculum for learning kidney and liver transplantation in the rat.

During the education of the next generation of scientists in experimental research, careful instruction in surgical techniques is of major importance. This applies in particular to complicated microsurgical models, which require a structured teaching concept with clearly laid-down working steps and adequate didactic resources. Transplantations in rats are undoubtedly among the most difficult models in experimental surgery. Because completely sutured orthotopic liver transplantation and kidney transplantation have been practiced for many years in our Surgical Research Unit, techniques must be transmitted to future generations. A microsurgical training program has been set up with the aim of being efficient, transparent, and motivating. Simply learning-by-doing in the sense of "laissez-faire" is ineffective and costly. Our training program is based on "three-phase didactics," in which the learning targets are presented in sequence and are clearly defined. This report is intended to give a brief overview of the principal transplantation models and to serve as a guide for teaching these models.

Animals↗

PubMed2005

Cyclic loading comparison between biodegradable interference screw fixation and biodegradable double cross-pin fixation of human bone-patellar tendon-bone grafts.

PURPOSE: The aim of this study was to compare ultimate load, yield load, stiffness, and displacement after cyclic loading of a cross-pin technique and an interference screw technique for the fixation of bone-patellar tendon-bone (BPTB) grafts in anterior cruciate ligament (ACL) reconstruction. TYPE OF STUDY: Biomechanical in vitro study. METHODS: The devices tested were 2 2.7-mm biodegradable pins (RigidFix; Ethicon, Mitek Division, Norderstedt, Germany) and biodegradable interference screws (Absolute; Innovasive Devices, Marlborough, MA). Each device was used for the fixation of 10 8-mm, 9-mm, or 10-mm sized human BPTB grafts in tunnels drilled in bovine knees. Ultimate load, yield load, stiffness, and displacement after cyclic loading (1,000 cycles between 50 and 250 N) were then evaluated. RESULTS: All 8-mm grafts that were fixed with cross-pins failed after a mean of 124 cycles of load. The 9-mm and 10-mm grafts survived the cyclic loading protocol. Yield load and maximum load of the 10-mm groups (cross-pin and interference screw) were significantly higher than that of the 9-mm groups. There was no significant difference in maximum load, yield load, and stiffness between the cross-pin and interference screw fixation technique for 1 graft size. CONCLUSIONS: The biomechanical data suggest that femoral fixation of 9-mm and 10-mm BPTB grafts using 2.7-mm biodegradable cross-pins leads to primary stability that is comparable to that of biodegradable interference screws. Fixation of 8-mm BPTB grafts using 2.7-mm biodegradable cross-pins had poor results. CLINICAL RELEVANCE: The diameter of the bone block is the limiting factor for the final fixation strength and the cyclical survival when using cross-pins. We strongly recommend not using this technique for bone blocks smaller than 9 mm in diameter.

Absorbable Implants↗

PubMed2005

Coma and respiratory failure in a child with severe vitamin B(12) deficiency.

OBJECTIVE: Psychofunctional follow-up of severe vitamin B(12) deficit. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: Ten-month-old boy. INTERVENTION: Follow-up at 3 yrs. MEASUREMENTS AND MAIN RESULTS: A 10-month-old boy was admitted to the pediatric intensive care unit with respiratory failure, muscular hypotonia, and involuntary movements. Although a central nervous system infection was excluded, computed tomography scan showed a diffuse cortical-subcortical atrophy. Vitamin B(12) deficiency was suspected because of a red-cell count of 1,350,000/mm(3) and a hemoglobin value 5.9 g/dL (MCV 116). The baby had been exclusively breast-fed, but his mother had been a strict vegan for 10 yrs. Chronic dietary vitamin B(12) deprivation was confirmed by blood and urinary samples. Treatment with vitamin B(12) led in 2 wks to rapid and complete hematological improvement and to partial regression of neurologic symptoms. During the following 3 yrs the boy had normal vitamin intake and underwent intensive rehabilitative treatment. The brain atrophy regressed, but linguistic and psychomotor delay persisted. CONCLUSIONS: Rapid clinical improvement after vitamin supply does not correlate with a complete recovery.

Breast Feeding↗

PubMed2005

The use of indomethacin in the treatment of plateau waves: effects on cerebral perfusion and oxygenation.

OBJECT: Plateau waves are sudden and steep increases in intracranial pressure (ICP) that can develop in patients with cerebral injuries, reduced pressure-volume compensatory reserve, and preserved autoregulation. They are caused by cerebral vasodilation in response to a reduction in cerebral perfusion and are associated with increased cerebral blood volume and reduced cerebral blood flow. The authors evaluated the hypothesis that administration of indomethacin, a potent cerebral arteriolar vasoconstrictor, could interrupt the vicious cycle that occurs during plateau waves, extinguishing these waves and, ultimately, restoring cerebral perfusion and oxygenation. METHODS: Plateau waves developed in nine patients, seven with severe traumatic brain injury and two with intraparenchymal hemorrhage. One to four episodes of plateau waves per patient were treated with indomethacin (15-20 mg), which was delivered by an intravenous bolus injection. Each patient's mean arterial blood flow (MABP), ICP, cerebral perfusion pressure (CPP), and cerebral tissue PO2 were continuously monitored and the data obtained were stored in a personal computer. Each patient's jugular venous O2 saturation (SjvO2) and venoarterial difference in PCO2 were evaluated by intermittent blood sampling. During five episodes of plateau waves, middle cerebral artery flow velocities were evaluated by transcranial Doppler ultrasonography. Indomethacin extinguished all plateau waves. On average, the ICP decreased from an initial value of 58.9 +/- 11.6 mm Hg to 21.2 +/- 8.6 and 25.8 +/- 13.7 mm Hg after 5 and 10 minutes, respectively (p < 0.01). The MABP did not change significantly. As a consequence the CPP increased by 98 and 81% after 5 and 10 minutes, respectively (p < 0.01). Five and 10 minutes after indomethacin was administered, SjvO2 increased from an initial value of 50 +/- 10.5% to 62 +/- 7.6 and 59.9 +/- 9.3%, respectively (p < 0.01); the cerebral tissue PO2 increased from an initial value of 13.4 +/- 10.6 mm Hg to 23.6 +/- 9.58 and 21.9 +/- 9.2 mm Hg, respectively (p < 0.05); and the venous-arterial PCO2 decreased significantly. The mean and diastolic flow velocities increased significantly, whereas the pulsatility index decreased from 1.39 +/- 0.56 to 1.09 +/- 0.4 at 5 minutes and 1.06 +/- 0.36 at 10 minutes (p < 0.05). CONCLUSIONS: The findings confirm that plateau waves are caused by vasodilation and show that indomethacin, by constricting the cerebral arteries, is effective in extinguishing plateau waves, ultimately restoring cerebral perfusion and oxygenation.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Tumor-associated CD75s gangliosides and CD75s-bearing glycoproteins with Neu5Acalpha2-6Galbeta1-4GlcNAc-residues are receptors for the anticancer drug rViscumin.

The anticancer drug rViscumin, currently under clinical development, has been shown in previous studies to be a sialic acid specific ribosome inactivating protein (RIP). Comparative binding assays with the CD75s-specific monoclonal antibodies HB6 and J3-89 revealed rViscumin to be a CD75s-specific RIP due to identical binding characteristics toward CD75s gangliosides. The receptor gangliosides are IV6nLc4Cer, VI6nLc6Cer, and the newly characterized ganglioside VIII6nLc8Cer, all three carrying the Neu5Acalpha2-6Galbeta1-4GlcNAc motif. To elucidate the clinical potential of the rViscumin targets, CD75s gangliosides were determined in several randomly collected gastrointestinal tumors. The majority of the tumors showed an enhanced expression of CD75s gangliosides compared with the unaffected tissues. The rViscumin binding specificity was further investigated with reference glycoproteins carrying sialylated and desialylated type II N-glycans. Comparative Western blots of rViscumin and ricin, an rViscumin homologous but galactoside-specific RIP, revealed specific recognition of type II N-glycans with CD75s determinants by rViscumin, whereas ricin failed to react with terminally sialylated oligosaccharides such as CD75s motifs and others. This strict binding specificity of rViscumin and the increased expression of CD75s gangliosides in various tumors suggest this anticancer drug as a promising candidate for an individualised adjuvant therapy of human tumors.

Antibodies, Monoclonal↗

PubMed2004

Cytotoxicity of the novel anti-cancer drug rViscumin depends on HER-2 levels in SKOV-3 cells.

rViscumin is a recombinant mistletoe lectin under clinical investigation as new anti-cancer drug. The relationship between oncogene, e.g., HER-2/neu (c-erbB2) receptor activation and tumor cell chemosensitivity, is of considerable importance to better predict the response to chemotherapy. Here, we analyze the cellular and molecular effects of HER-2 expression on rViscumin chemotoxicity in SKOV-3 cells. We show that selective depletion of HER-2 by ribozyme-targeting markedly decreases cellular sensitivity towards rViscumin. These findings are confirmed by treatment with the well-established inhibitory HER-2 antibody trastuzumab (Herceptin). Using clonal ribozyme-transfected cell lines, we establish a 'HER-2 gene dose' dependence of rViscumin cytotoxicity, which is due to differential induction of apoptosis and is not mediated by cell cycle alterations or altered cellular rViscumin binding/internalization. We further demonstrate an rViscumin-mediated, HER-2-dependent down-regulation of bcl-2 and the dose-dependent activation of members of the MAPK family, p42/44, SAPK/JNK, and p38, but not of caspases-3 and -7.

Antibodies, Monoclonal↗

PubMed2004

Mistletoe lectin I is a sialic acid-specific lectin with strict preference to gangliosides and glycoproteins with terminal Neu5Ac alpha 2-6Gal beta 1-4GlcNAc residues.

Mistletoe lectin I (ML-I) is a type II ribosome-inactivating protein, which inhibits the protein biosynthesis at the ribosomal level. ML-I is composed of a catalytically active A-chain with rRNA N-glycosidase activity and a B-chain with carbohydrate binding specificities. Using comparative solid-phase binding assays along with electrospray ionization tandem mass spectrometry, ML-I was shown to preferentially bind to terminally alpha2-6-sialylated neolacto series gangliosides from human granulocytes. IV(6)Neu5Ac-nLc4Cer, VI(6)Neu5Ac-nLc6Cer, and VIII(6)Neu5Ac-nLc8Cer were identified as ML-I receptors, whereas the isomeric alpha2-3-sialylated neolacto series gangliosides were not recognized. Only marginal binding of ML-I to terminal galactose residues of neutral glycosphingolipids with a Galbeta1-4Glc or Galbeta1-4GlcNAc sequence was determined, whereas a distal Galalpha1-4Gal, GalNAcbeta1-3Gal, or GalNAcbeta1-4Gal disaccharide did not bind at all. Among the glycoproteins investigated in Western blot and microwell adsorption assays, only those carrying Neu5Acalpha2-6Galbeta1-4GlcNAc residues, exclusively, predominantly, or even as less abundant constituents in an assembly with Neu5Acalpha2-3Galbeta1-4GlcNAc-terminated glycans, displayed high ML-I binding capacity. From our data we conclude that (i) ML-I has to be considered as a sialic acid- and not a galactose-specific lectin and (ii) neolacto series gangliosides and sialoglycoproteins with type II glycans, which share the Neu5Acalpha2-6Galbeta1-4GlcNAc terminus, are true ML-I receptors. This strict preference might help to explain the immunostimulatory potential of ML-I toward certain leukocyte subpopulations and its therapeutic success as a cytotoxic anticancer drug.

Adsorption↗

PubMed2003

Maternal health outcomes in Europe.

OBJECTIVES: To use PERISTAT data on indicators of maternal mortality and morbidity to explore maternal health outcomes in Europe, and to discuss the implications of variations in the data sources for these indicators. STUDY DESIGN: The PERISTAT feasibility study provides the source for this descriptive study, covering 15 European countries. Maternal mortality ratios are calculated, and data to describe maternal mortality by age, cause of death and mode of delivery are pooled for the countries that provided data. RESULTS: Data presented show an increased risk of maternal death among older mothers and for caesarean sections compared with other modes of delivery, and the three most prevalent causes of maternal deaths reported were embolism, hypertensive diseases of pregnancy, and haemorrhage. CONCLUSIONS: Variations in maternal mortality ratios reflect different data sources with varying levels of ascertainment in addition to differences in the number of maternal deaths. Further development is needed to construct comparable indicators of maternal morbidity.

Adult↗

PubMed2003

Cerebral perfusion pressure and cerebral tissue oxygen tension in a patient during cardiopulmonary resuscitation.

OBJECTIVE: To report on the effects of cardiopulmonary resuscitation (CPR) instituted immediately after a cardiac arrest on cerebral perfusion pressure (CPP) and cerebral tissue oxygen tension (PbrO(2)). DESIGN: Case report. SETTING: ICU of a university hospital. PATIENT: A head-injured 17-year-old man submitted to multimodal neurological monitoring underwent sudden cardiac arrest and successful CPR. INTERVENTIONS: External chest compression, 100% oxygen ventilation, volume expansion and standard ACLS protocols. MEASUREMENTS AND RESULTS: Heart rate, ECG, mean arterial blood pressure (MABP), ETCO(2), PaO(2), intracranial pressure (ICP), CPP and PbrO(2) were continuously monitored during CPR and data recorded at 15-s intervals by a dedicated personal computer. At the onset of the cardiac arrest, PbrO(2) decreased to zero. The institution of CPR resulted in a progressive increase of MABP, CPP and PbrO(2). Assuming, on the basis of previous experimental and clinical reports, 8 mmHg PbrO(2) as a possible ischaemic/hypoxic threshold value, during the first 6.5 min of CPR, PbrO(2) values were below this threshold (range 0-7 mmHg) and CPP values were <25 mmHg for 81.5% of the time. In the following 5.5 min, more efficient CPR generated CPP values >25 mmHg for 77.3% of the time. These values were associated with a PbrO(2) >8 mmHg (range 8-28 mmHg) at all times. CONCLUSIONS: In the clinical setting of a witnessed cardiac arrest, immediate institution of CPR can be effective in generating PbrO(2) values above a supposed ischaemic/hypoxic threshold when CPP is >25 mmHg. PbrO(2) monitoring by the Licox system is sensitive and reliable, even at low values, and can be suitable for evaluating cerebral oxygenation during experimental CPR.

Adolescent↗

PubMed2003

Detection of rViscumin in plasma samples by immuno-PCR.

To allow for pharmacokinetic studies in adjunction with the current clinical developments of the potent cytostatic anti-cancer drug rViscumin, a sandwich immuno-PCR (IPCR) assay was developed for the detection of rViscumin in blood plasma. The IPCR was carried out with a commercially available reagent kit, consisting of pre-assembled rViscumin-specific antibody-DNA conjugates as well as a specific competitor DNA fragment to be amplified by PCR. Various combinations of capture- and detection-antibodies were compared for performance in IPCR. Using the optimized assay, as few as 50 zeptomol (approx. 100 fg/ml) rViscumin (MW 57 kDa) was detectable in standardized human serum samples. The IPCR assay was very selective for rViscumin and in spiking experiments in proband plasma samples, signal recovery rates between 70% and 120% were obtained. The linear sensitivity range of the assay covered more than five orders of magnitude. Repeated measurements of rViscumin resulted in a mean standard deviation value of 14.2%.

Animals↗

PubMed2003

Reduction of preeclampsia in multiple pregnancies by a dedicated monitoring protocol.

OBJECTIVE: To evaluate the effect of a dedicated monitoring protocol on the incidence of pregnancy-induced hypertension disorders (preeclampsia, HELLP [hemolysis, elevated liver enzymes, low platelets] syndrome, gestational hypertension) during a 5-year period in 417 women with multiple gestations. METHODS: At the Department of Obstetrics and Fetomaternal Medicine, Vienna University, an outpatient care protocol for women with multiple pregnancies was established. Between March 1997 and February 2002, 379 twins and 38 triplets were followed up. Mean visits of dichorial and monochorial twins were nine and 11, respectively. Triplets were asked to at least 12 follow-up visits. RESULTS: Any kind of pregnancy-associated hypertensive disorders necessitating cesarean delivery developed in eight women (seven with twins, one with triplets; 1.76%). Three cases of preeclampsia, three cases of HELLP syndrome, and two cases of pregnancy-induced hypertension were diagnosed. Perinatal outcome of all 17 newborns was excellent without any mortality and only minor morbidity. All mothers left the hospital in a fully recovered condition. CONCLUSION: Because of our results we hypothesize that our monitoring protocol with frequent visits, continuous personal obstetric care, and timed delivery is effective in reduction of pregnancy-induced hypertension in multiple pregnancies.

Adult↗

PubMed2003

Elective cesarean section vs. spontaneous delivery: a comparative study of birth experience.

BACKGROUND: To investigate birth experience and medical outcome in women with elective cesarean section (CS) compared with women with intended vaginal delivery. METHODS: A total of 1050 pregnant women were included in this prospective trial. Psychological factors, pain levels and birth experience were investigated using a self-designed questionnaire and three established psychological tests in gestational week 38, and 3 days and 4 months postpartum. In addition, medical data were evaluated from the records. RESULTS: Out of 903 women with planned vaginal birth, in 484 women (53.6%) minimal perineal surgery had to be performed after birth, 41 women (4.5%) had vacuum deliveries, and in 93 cases (10.3%) emergency CS had to be performed. In the 147 elective CS (103 based on medical and 44 on psychological factors), a significantly lower rate of maternal and fetal complications was observed when compared with vaginal birth (5.4% vs. 19.3%; p < 0.0001). Birth experience (Salmon test) was significantly better in elective CS compared with vaginal delivery, but worse in women with emergency CS and worst in those with vacuum delivery. We found that 83.5% of women with vaginal delivery would choose the same mode of birth again, 74.3% of women with CS on demand, and 66% of women with medically necessary CS. Only 30.1% of women with emergency CS wanted to receive CS at the next birth. CONCLUSIONS: Elective CS is a safe and psychologically well tolerated procedure. The results are comparable with uncomplicated vaginal delivery and far superior to secondary intervention such as vacuum delivery or emergency CS.

Adolescent↗

PubMed2003

Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy.

AIMS: To assess the effects of maternal buprenorphine treatment at conception and during pregnancy on neonates in terms of birth outcomes and neonatal abstinence syndrome (NAS). DESIGN AND SETTING: Prospective, open-label, out-patient maintenance, case report study, conducted at the drug addiction out-patient clinic at the University Hospital Vienna. PARTICIPANTS: Two buprenorphine-maintained pregnant women who had conceived during buprenorphine treatment. Both patients had previously given birth to healthy neonates following induction on to buprenorphine maintenance therapy in the second trimester. MEASUREMENTS: Mothers: urinalysis. Neonates: gestational age at delivery, Apgar scores, birth weight, length and NAS (Finnegan Scale). FINDINGS: Urinalyses were negative for both women for 25 and 38 months, respectively, during the pregnancy period. There were no complications during the course of the pregnancy. The newborns delivered by both women were healthy, birth outcomes were within normal ranges and there were no NAS symptoms requiring treatment. CONCLUSIONS: To our knowledge this is the first report detailing the pregnancies of women treated with buprenorphine at the time of conception and investigated in a prospective study. The NAS noted in neonates born to buprenorphine-maintained mothers appears to be less severe than the NAS observed in neonates born to methadone-maintained mothers. These preliminary data indicate that, in our patient cohort, buprenorphine maintenance at the time of conception and during pregnancy did not seem to affect birth outcome measurements such as pregnancy complications, week of delivery, birth weight, length, umbilical pH or neurodevelopmental progress. Future prospective studies with larger study populations are warranted.

Adult↗

PubMed2002

Preferential binding of the anticancer drug rViscumin (recombinant mistletoe lectin) to terminally alpha2-6-sialylated neolacto-series gangliosides.

Production of biochemically defined recombinant mistletoe lectin was achieved by cloning and separate expression of the single catalytically active A-chain and the B-chain with carbohydrate binding properties in Escherichia coli, yielding an active heterodimeric protein named rViscumin (Eck et al. [1999] Eur. J. Biochem., 265, 788-797). Employing solid phase binding assays, rViscumin was shown to preferentially bind to terminally alpha2-6-sialylated neolacto-series gangliosides IV(6)Neu5Ac-nLc4Cer, VI(6)Neu5Ac-nLc6Cer, and VIII(6)Neu5Ac-nLc8Cer isolated from human granulocytes. Only marginal binding of rViscumin to galactose-terminated neutral GSLs was determined, whereas reinvestigation of ricin specificity demonstrated this lectin as a galactose-binding protein. Human promyelotic HL-60 cells exhibited an IC(50) value (half maximum cytotoxicity) of 1.16 pM and human bladder carcinoma 5637 cells of 12.1 pM rViscumin; CHO-K1 cells were resistant to rViscumin treatment up to a concentration of 5.26 nM tested. Quantification of the predominant receptor ganglioside IV(6)Neu5Ac-nLc4Cer by means of a specific anti-Neu5Acalpha2-6Galbeta1-4GlcNAc-R antibody revealed 3.68 x 10(6) and 1.54 x 10(6) receptor molecules per HL-60 and 5637 cell, respectively; CHO-K1 cells were negative, lacking alpha2-6-sialylated gangliosides. The data imply a direct correlation of rViscumin cytotoxicity and the expression of receptor ganglioside. Moreover, CHO-K1 cells were rendered susceptible toward rViscumin cytotoxicity after exogenous application of human granulocyte gangliosides. Thus, (1) rViscumin has to be considered as a sialic acid-specific rather than a galactose-specific type II ribosome-inactivating protein, and (2) neolacto-series gangliosides with Neu5Acalpha2-6Galbeta1-4GlcNAc-terminus are true functional and physiologically relevant rViscumin receptors.

Animals↗

PubMed2002

Immunoadsorption and plasma exchange in pregnancy.

BACKGROUND: During pregnancy, familial hyperlipidemia or systemic lupus erythematosus (SLE) can exacerbate having devastating consequences for both mother and fetus. Immunoadsorption is established for removal of pathogenic proteins lipoproteins or autoantibodies, but this procedure has only rarely been used in pregnancy. METHODS: We evaluated retrospectively 126 extracorporeal treatments during six pregnancies. Forty low-density lipoprotein immunoadsorptions, 6 sole plasma exchanges and 36 combined procedures (plasma exchange followed by immunoadsorption) were performed for severe hypertriglyceridemia, complicated by acute pancreatitis. Forty-four IgG immunoadsorptions were executed in 2 pregnant women suffering from SLE with a disastrous course during prior pregnancies. RESULTS: In hyperlipidemic pregnant women, mean triglyceride levels prior to treatment were 3,841 +/- 2,076 mg/dl (mean +/- SD) and total cholesterol was 617 +/- 354 mg/dl. Until delivery, a 27% reduction of triglycerides could be achieved. Clinical and serological signs of pancreatitis disappeared after initiation of extracorporeal therapy. Four healthy babies were delivered (birthweights between 2,250 and 3,360 g). In 1 woman suffering from SLE, intrauterine fetal death occurred in the 22nd week of gestation despite a reduction of cardiolipin antibodies by 69%. The second case (a twin pregnancy) was complicated by steroid-resistant antibody-mediated anemia. Due to frequent immunoadsorptions, red blood cell count improved (reduction of antierythrocyte antibodies by 66.6%) and 2 healthy babies (birthweights 2,120 and 2,350 g) were delivered by cesarean section. CONCLUSION: Long-term antibody-based immunoadsorption has been demonstrated to be safe and well tolerated in pregnant women and enables normal intrauterine/fetal development. Although rarely indicated during pregnancy, this treatment modality might be a promising new technique for removal of autoantibodies and lipoproteins in patients with serious gestational complications without sufficient response to conventional therapy.

Adsorption↗