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Biomedical subjects

B Lange

Publications and source records attributed to B Lange.

At least 19 recordsLinked to original sources
PubMed2006

Persistence of viral RNA in rabbits which overcome an experimental RHDV infection detected by a highly sensitive multiplex real-time RT-PCR.

An internally controlled multiplex real-time RT-PCR using TaqMan probes and external standards for absolute RNA quantification was developed as a new diagnostic tool for the detection of rabbit haemorrhagic disease virus (RHDV). The test revealed a specificity of 100%, an analytical sensitivity of 10 copies/well and a linearity over a range from 10(1) to 10(10) copies. The viral loads in organs, leukocytes, sera and excretions of seropositive, convalescent rabbits which were overcoming an experimental infection with RHDV were determined using the validated assay. As a result, viral RNA was demonstrated and quantified for at least 15 weeks. Thus, a persistence of viral RNA after experimental infection of rabbits could be shown for the first time. In contrast, neither antigen nor infectious virus could be detected by antigen-ELISA, immunohistochemistry or experimental transmission. Therefore, further experiments are necessary to prove that the persistence of RNA is linked with the persistence of infectious virus particles.

Animals↗
PubMed2006

A Bayesian meta-analysis of prophylactic granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in children with cancer.

The purpose of this analysis was to examine the efficacy of prophylactic hematopoietic colony-stimulating factors (CSFs) in pediatric cancer and to describe how a Bayesian meta-analysis can be conducted and then modified to incorporate information not readily included in a frequentist meta-analysis. Three Bayesian models were developed. The simplest model used the same data as a published frequentist meta-analysis. The second model included data that could not easily be incorporated into the frequentist meta-analysis, including data from different courses of chemotherapy and continuous outcomes that did not report variance estimates. The third model examined the effect of CSF type (granulocyte CSF vs. granulocyte-macrophage CSF). Compared with the frequentist model, the Bayesian model with the most data suggested a greater benefit of CSFs, with a 3.2-day reduction in duration of parenteral antibiotics (95% credible interval: -7.1, 0.7) in the expanded Bayesian model compared with a 0.8-day (95% confidence interval: -2.3, 0.7) reduction in the frequentist model. Bayesian meta-analysis also suggested that, compared with granulocyte-macrophage CSF, granulocyte CSF was associated with a 4.8-day decrease in the duration of parenteral antibiotics. Bayesian meta-analysis can readily include information not easily incorporated in a frequentist meta-analysis. Some treatment effect estimates were larger by a clinically important amount when additional data contributed to the pooled estimate.

Bayes Theorem↗
PubMed2005

Effect of dislodging techniques on foliar residue determination for agricultural crops.

The Agricultural Reentry Task Force (ARTF) conducted a study to determine whether different dislodgeable foliar residue (DFR) techniques had any effect on the amount of residues dislodged from the leaves of vegetable crops. Four previously employed techniques were evaluated with two chemicals (carbaryl and methomyl) on two crops (cabbage and lettuce). Carbaryl, a moderately water-soluble chemical, was applied at a rate of 2.0 lbs active ingredient/acre (lb ai/A) while methomyl, a highly water soluble chemical, was applied at a rate of 0.9 lb ai/A. One day after application, leaf punches were collected and the residues were dislodged following one of four techniques that differed in the number of dislodgings per sample, the duration of dislodging, the solution volume, and/or the type of solution used. The results indicated that three of the techniques gave similar results, whereas a fourth gave marginally lower results.

Carbaryl↗
PubMed2005

Postremission therapy for children with acute myeloid leukemia: the children's cancer group experience in the transplant era.

We reviewed consolidation therapy results and analyzed postremission outcomes for 1464 children less than 21 years old at diagnosis in five consecutive Children's Cancer Group acute myeloid leukemia trials between 1979 and 1996. Children in remission were allocated to allogeneic bone marrow transplantation (BMT) (N=373) in first remission, if a matched family donor was available. Remaining children were assigned consolidation chemotherapy (N=688) or autologous purged BMT (N=217), or withdrew from study before assignment, or with unknown data (N=186). Overall and disease-free survival were superior for children assigned allogeneic transplants. High (>50,000/microl) diagnostic white blood cell (WBC) count was prognostic for inferior outcome, but French-American-British (FAB) subtypes were not. Inv(16) is a favorable karyotypic feature for children in first remission and t(8;21) is not. Allogeneic transplantation benefit was evident in most children, including those with high or low diagnostic WBC count, each FAB subtype, and t(8;21), but was not seen in children with inv(16). Therefore, these data suggest reserving matched related donor allogeneic transplantation for children with inv(16) for second remission, but not those with t(8;21).

Acute Disease↗
PubMed2005

[Physiologic requirements of high level gymnastics].

The evolution of the physiological profile of gymnasts over the past 40 years is outlined. Generally, gymnasts have a low aerobic aptitude in spite of an increase in the number of training hours. During the last decades, anaerobic power of gymnasts has increased. And now, the maximal power output measured by the Wingate test in high level male gymnasts is between 12 and 14 W.Kg-1 and in female gymnasts between 10 and 12 W.Kg-1. Measurement of higher blood lactate values also confirms that the anaerobic capacity has increased.

Gymnastics↗
PubMed2004

Staged informed consent for a randomized clinical trial in childhood leukemia: impact on the consent process.

BACKGROUND: Children Cancer Group (CCG) 1991 is the first childhood acute lymphoblastic leukemia trial within CCG that allowed the utilization of a staged approach to the consent process. METHODS: One hundred and forty subjects participated in the Project on Informed Consent which compared the primary outcome measures in the consent process of patients enrolled in CCG-1991 with those enrolled in other CCG leukemia studies. RESULTS: The parents' trust scores were higher for the CCG-1991 compared with other protocols. Eighty percent of parents enrolled in CCG-1991 understood the distinction between the randomized clinical trial and the standard treatment arm, compared with 62.5% in the other studies, P = 0.05. Multiple other outcome measures suggested a positive impact from staged informed consent. CONCLUSIONS: Our results suggest that a consent process with a staged approach can help investigators obtain a more truly informed consent. Future research is needed to confirm the benefits of the staged approach to the informed consent process.

Child↗
PubMed2004

Effect of intranasal fluticasone propionate and triamcinolone acetonide on basal and dynamic measures of hypothalamic-pituitary-adrenal-axis activity in healthy volunteers.

BACKGROUND: Most published studies show that intranasal corticosteroids have no effect on the hypothalamic-pituitary-adrenal (HPA) axis, but there have been isolated reports to the contrary, contradicting accumulated knowledge on pharmacokinetics. OBJECTIVE: To re-evaluate the effect of fluticasone propionate aqueous nasal spray (FPANS) and triamcinolone acetonide (TAA) aqueous nasal spray on the HPA axis using an improved study design. METHODS: Twenty-three healthy volunteers were randomized in a double-blind, three-way crossover study. The study comprised a 4-day placebo run-in phase followed by three 4-day treatment periods (placebo, FPANS (200 microg once daily) or TAA aqueous nasal spray (220 microg once daily)), separated by 7-14 days washout intervals. Before the first, and on the last day of each treatment period, 12-h overnight urine was collected to assess cortisol excretion and cortisol creatinine ratio. Approximately 26 h after the last administration of study medication, volunteers underwent stimulation with 0.5 microg adrenocorticotropic hormone (ACTH). Serum cortisol concentrations were measured before and 20 and 30 min after injection. Blood and urine samples were analysed for cortisol by liquid chromatography tandem mass spectrometry. RESULTS: Compared with placebo, EP or TAA had no significant effect on mean overnight (12 h) urinary cortisol excretion, and did not significantly suppress the overnight geometric mean urinary cortisol/creatinine excretion ratio. Values for serum cortisol before and after ACTH simulation showed no significant suppression, although there was a slight blunting of the HPA-axis response following TAA treatment. CONCLUSION: This study confirms that there are no detectable effects on the HPA axis following short-term intranasal FP or TAA at their recommended dosages.

Administration, Intranasal↗
PubMed2004

Classical swine fever virus Strain 'C'. How long is it detectable after oral vaccination?

To determine the persistence period of C-strain vaccine virus in immunized animals, domestic pigs and wild boars were vaccinated orally and killed on different days post vaccinationem (dpv). Tissue samples were taken at necropsy from both species for detection of C-strain virus. From domestic pigs nasal swabs and faeces were also collected. During the investigation period (2-12 dpv) vaccine virus could never be detected in nasal secretions and in faeces of vaccinated domestic pigs. In contrast, C-strain virus was found in organs until day 8 pv in domestic pigs and until day 9 pv in wild boars. Whereas in domestic pigs virus was detected in tonsils, Ln. mandibularis or in spleen, in wild boar it only was found in tonsils. We conclude that C-strain vaccine virus is not detectable in wild boars longer than 10-12 days after intake of the vaccine baits.

Administration, Oral↗
PubMed2003

Vaccination with minigenes encoding for novel 'self' antigens are effective in DNA-vaccination against neuroblastoma.

The induction of T-cell mediated immunity against neuroblastoma is a challenge due to poor immunogenicity of this malignancy. Here, we demonstrate the induction of protective immunity in a syngeneic murine neuroblastoma model following vaccination with minigenes comprising of three novel natural MHC class I ligands. First, after immunoprecipitation of MHC class I from NXS2 cells, peptides were eluted and examined in tandem-MS analysis which lead to the identification of three novel natural MHC class I peptide ligands, TEALPVKLI from ribonucleotide reductase M2, NEYIMSLI from Ser/Thr protein phosphatase 2A and FEMVSTLI with unknown origin. Second, we constructed two different minigenes, one encoding for the three novel epitopes and the second for three known mTH derived epitopes with high predicted binding affinity to MHC class I by cloning them into the mammalian expression vector pCMV-3FUB. This lead to constructs with an ubiquitin-tag upstream the inserted epitopes in order to facilitate proteasomal degradation. Furthermore the epitopes were separated by a spacer peptide (AAY), which proved to be a preferential proteasome cleavage site. Third, we demonstrate the induction of protective immunity against neuroblastoma using an attenuated strain of Salmonella typhimurium as a carrier harboring pCMV 3FUb vectors encoding for the two minigenes. These findings establish proof of concept that disruption of self tolerance against neuroblastoma associated epitopes may be an effective adjuvant therapeutic strategy.

Animals↗
PubMed2003

Neuroblastoma directed therapy by a rational prodrug design of etoposide as a substrate for tyrosine hydroxylase.

Tumor directed cytotoxic therapy is one of the major challenges for the success of chemotherapy. In order to accomplish this goal in neuroblastoma, we rationally designed a prodrug of etoposide as substrate for tyrosine hydroxylase, a well established neuroblastoma associated enzyme. Here, we report synthesis and characterization of a 3,4 dihydroxy-phenyl carbamate derivative of etoposide. In order to demonstrate activation by tyrosine hydroxylase, the coding sequence of murine tyrosine hydroxylase was generated by reverse transcriptase-polymerase chain reaction from NXS2 neuroblastoma cells and cloned into the pRSET-A bacterial expression vector. The enzyme was expressed in Escherichia coli, characterized by Western blot and enzymatic activity was demonstrated by conversion of tyrosine into DOPA in the presence of cofactors using reversed phase high-performance liquid chromatography. Under these enzymatic conditions, we demonstrate conversion of 3,4 dihydroxy-phenyl carbamate prodrug into free etoposide. This effect was clearly mediated by the enzyme since bacteria transformed with the empty vector were ineffective of prodrug activation. Furthermore, tyrosine hydroxylase positive cells exposed to the etoposide prodrug were effectively killed in contrast to tyrosine hydroxylase negative controls. These findings demonstrate that etoposide can be designed as a prodrug substrate for tyrosine hydroxylase and thereby establish proof of concept for neuroblastoma directed enzyme prodrug therapy.

Animals↗
PubMed2003

Rationally designed hydrolytically activated etoposide prodrugs, a novel strategy for the treatment of neuroblastoma.

Effective chemotherapy in neuroblastoma is limited by poor anti-tumor efficacy, systemic toxicity and the induction of drug resistance. Here, we provide further evidence that a hydrolytic activated prodrug design may overcome these problems. For this purpose, VP-16 was functionally blocked by a carbonate linker to generate two novel chemically stable prodrugs of VP-16, ProVP-16 I and II. We demonstrate profoundly different biological effects in vitro and in vivo of the prodrugs compared to parental VP-16. First, we established an up to >2 log higher in vitro toxicity of the two prodrugs compared to VP-16 on a panel of neuroblastoma cell lines. The highest increase of prodrug mediated cytotoxicity was observed in multi drug resistant cell lines. Second, in vivo studies showed a maximum tolerated dose (MTD) of ProVP-16 II (60 mg/kg), which was at least threefold higher than that of VP-16 (20 mg/kg). Tests of ProVP-16 II in a syngeneic NXS2 neuroblastoma model indicated that mice treated with this prodrug at 1/3 of the MTD was as effective as VP-16 parental compound used at the MTD in suppression of tumor growth. In summary, the etoposide prodrugs proved effective and less toxic and are therefore highly promising new anti-neuroblastoma compounds.

Animals↗
PubMed2003

Paralysis of the femoral nerve following totally extraperitoneal laparascopic inguinal hernia repair.

Totally extraperitoneal preparation (TEP) of an inguinal hernia is an established method of treating inguinal hernias associated with an acceptable complication rate (2-12%) and low rate of recurrence (0-3%). This is the first reported case of sensorimotor paralysis of the femoral nerve following the complete endoscopic mesh treatment of a primary inguinal hernia to the left side. Following a discussion of the necessary diagnostic and therapeutic steps, traumatic postsurgical paralysis of the nerve as well as spontaneous paralysis of the femoral nerve are discussed. The prognosis is positive given the lack of macroscopic evidence of any direct damage to the nerve.

Femoral Neuropathy↗
PubMed2002

Mesh penetration of the sigmoid colon following a transabdominal preperitoneal hernia repair.

The laparascopic transabdominal preperitoneal (TAPP) repair of an inguinal hernia is an established technique associated with notably low rates of recurrence and complication. Inguinal pain and anal bleeding following a TAPP procedure may result from the penetration of the repair mesh into the sigmoid colon. In this case report, we discuss this particular complication following the TAPP procedure. Subsequently, we describe the diagnostics as well as the surgical treatment necessary.

Colon, Sigmoid↗
PubMed2002

Up-regulation of IL-18 in allergic rhinitis.

BACKGROUND: This paper reports a study on the concentrations of the pro-inflammatory cytokines IL-18 and IL-1beta in nasal secretions of allergic rhinitis patients in relation to ECP and nasal symptoms. METHODS: We measured IL-18 and IL-1beta concentrations using ELISA, and eosinophilic cationic protein (ECP) using the CAP system, in nasal secretions of 15 seasonal allergic rhinitis (SAR) patients at six visits throughout the pollen season. Pollen exposure, nasal and ocular symptoms were monitored daily. Furthermore, we measured IL-18, IL-1beta and ECP concentrations in nasal secretions of 19 controls and 20 symptomatic persistent allergic rhinitis (PAR) patients with house dust mite allergy. RESULTS: In SAR, the increase of IL-18, IL-1beta and ECP paralleled the pollen flight with a time delay. IL-18 and IL-1beta significantly increased during the pollen season compared to baseline, and differently from ECP, remained elevated until 4 weeks after the season. In PAR, the concentrations of IL-18 and ECP, but not IL-1beta, were significantly higher compared to controls, with IL-18 concentrations also being significantly higher than in SAR. CONCLUSION: This is the first study to demonstrate the up-regulation of IL-18 in nasal secretions in allergic rhinitis. The persistence of elevated IL-18 concentrations until after the season and the high concentrations in PAR compared to SAR suggests its role in persistent allergic inflammation.

Adult↗
PubMed2002

Clinical decision making in the acutely injured knee based on repeat clinical examination and MRI.

To determine the correlation between Magnetic Resonance Imaging (MRI) and clinical examination of the knee after an acute injury, and to see to what extent MRI affected the planned treatment, we examined 90 consecutive patients in a prospective study, clinically and with an extremity Magnetic Resonance (MR) scanner. The number of meniscal lesions, bone bruises and osteochondral lesions found on MRI was significantly higher than the clinical examinations indicated. Despite this, the treatment was only changed in 6 cases. In no case did MRI prevent a planned arthroscopy. MRI may reveal many clinically silent changes in the knee, also after minor injuries. The significance of these MRI findings must await long-term follow-up.

Acute Disease↗
PubMed2001

Oral immunisation against classical swine fever (CSF): onset and duration of immunity.

In an experimental study, onset and duration of immunity after oral immunisation of pigs with a classical swine fever (CSF) live virus vaccine based on the strain "C" has been evaluated. Sixteen weaner piglets (group 1) were orally instilled by syringe with the content of one vaccine bait whereas eighteen piglets (group 2) were fed with one bait. Six unvaccinated piglets represented the control group (group 3). The pigs having 2, 4, 6 and 10 days post vaccination (p.v.) were challenged with the highly virulent CSF virus (CSFV) strain "Koslov" to detect onset of immunity. After oral instillation of vaccine (group 1) the pigs were protected from a clinical infection 4 days p.v. One of four piglets reacted for a short time with an increase of body temperature. In group 2, a partial protection was already detected on day 2 p.v. On day 10 p.v., all animals were resistant to an experimental challenge infection. No protective neutralising antibodies were elicited until day 10 p.v. in both groups. Three animals of each group vaccinated orally against CSF were challenged approximately 6 and 10 months p.v. to evaluate duration of immunity. All vaccinated pigs developed neutralising antibodies and showed a protective immunity against an infection with CSFV until 10 months p.v. Furthermore, no vaccinated animal developed a viraemia after challenge. Altogether, 5 of 34 vaccinated pigs as well as all controls died after infection and showed typical gross lesions for CSF. The tonsils of the surviving pigs were negative for viral antigen by immunofluorescence.

Administration, Oral↗
PubMed2001

Patterns of memory performance in children with controlled epilepsy on the CVLT-C.

Decreased memory skills have been reported in children with epilepsy. However, standardized instruments to evaluate learning and memory in children have been unavailable until recently. The present study was designed to assess memory patterns in children with epilepsy based on the California Verbal Learning Test-Children's Version (CVLT-C). The test was administered to 44 children with complex partial seizures and 21 children with generalized seizures between 8 and 13 years of age. Children in the study had been treated for epilepsy for at least 6 months, had well-controlled seizures on monotherapy, and had no evidence of anticonvulsant toxicity. Children with head injuries, learning disabilities, or hyperactivity were excluded. Test results did not reflect differences in memory performance based on seizure type. Scores for the entire sample indicated intact new learning, decreased intrusions and perseverative responses, and better short-term than long-term delayed recall. Recognition skills were stronger than long-term delayed recall skills and suggested that memory performance may be improved for these children when a multiple-choice format is available in academic settings.

Child↗