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Biomedical subjects

E de Jong

Publications and source records attributed to E de Jong.

At least 19 recordsLinked to original sources

Observational study on efficacy, safety, and drug survival of anakinra in rheumatoid arthritis patients in clinical practice.

BACKGROUND: The efficacy and safety of anakinra, a recombinant human interleukin 1 (IL1) receptor antagonist used in rheumatoid arthritis, has been documented in five randomised controlled studies. However, long term post-marketing efficacy data are lacking. OBJECTIVE: To evaluate the efficacy, safety, and drug survival of anakinra in clinical practice. METHODS: All patients with rheumatoid arthritis who started anakinra in six hospitals between May 2002 and February 2004 were included in a two year prospective, in part retrospective, cohort study. Efficacy was assessed using the 28 joint disease activity score (DAS28) and the EULAR response criteria. Safety was evaluated using the common toxicity criteria. Drug survival and prognostic factors were analysed using Kaplan-Meier and Cox proportional hazard analyses. RESULTS: After three months, 55% of the patients (n = 146) showed a response (43% moderate, 12% good). A subset of patients continuing anakinra after 18 months had a sustained clinical response compared with patients who switched to other disease modifying antirheumatic drug treatment (DAS28 improvement, 2.46 v 1.79). Drug survival was 78%, 54%, and 14% after three, six, and 24 months, respectively. The reason for discontinuation was lack of efficacy in 78% and adverse events in 22%. Except for higher drug survival in women (odds ratio = 0.51, 95% confidence interval, 0.27 to 0.97), no prognostic factors were found. Adverse events were reported 206 times in 111 patients, the most common being injection site reactions (36%). Serious adverse events occurred in 12% of the patients, with one classified as related. CONCLUSIONS: The short term efficacy and safety profile of anakinra are comparable to those found in randomised clinical studies. However, the drug survival of anakinra after two years is low, mostly because of lack of efficacy.

Aged↗

[Female health care workers in the northern Netherlands].

Women have been members of the surgical guilds since as early as the 14th century. Decrees dating from the 16th-18th centuries demonstrate that a number of women made a living through surgical practice at that time. From the Middle Ages through to the 18th century, women played their role in medical practice, and were also involved in surgery. Apart from the common problems of the profession, these female practitioners also encountered difficulties related to their gender.

Female↗

[Hector Treub and his female students, the first women surgeons in the Netherlands].

Hector Treub (1856-1920), initially a surgeon trained by Van Iterson in Leiden, was appointed as professor in Gynaecology and Obstetrics in Leiden in 1887, and in 1896 he took on this position at the University of Amsterdam. He was a strong proponent of women training as medical specialists at a time where higher education for women was a matter of public debate. Treub was the first medical professor in the Netherlands who trained women in a surgical specialty, Heleen Brouwer-Robert (1887-1979), Rosalie Wijnberg (1887-1973) and Jeanne Knoop (1890-1975) were trained by him as surgically educated gynaecologists. Frieda van Hasselt (1891-1979) was trained by Van Rooy (1880-1937), former assistant and successor of Treub. These four women were the first female members of the Dutch Surgical Association, having joined this association during their surgical training.

Faculty, Medical↗

Analysis of retted and non retted flax fibres by chemical and enzymatic means.

Flax fibres (Linum usitatissimum L.) were subjected to chemical and enzymatic analysis in order to determine the compositional changes brought about by the retting process and also to determine the accessibility of the fibre polymers to enzymatic treatment. Chemical analysis involved subjecting both retted and non retted fibres to a series of sequential chemical extractions with 1% ammonium oxalate, 0.05 M KOH, 1 M KOH and 4 M KOH. Retting was shown to cause minimal weight loss from the fibres but caused significant changes to the pectic polymers present. Retted fibres were shown to have significantly lower amounts of rhamnogalacturonan as well as arabinan and xylan. In addition the average molecular mass of the pectic extracts was considerably lowered. Enzyme treatment of the 1 M KOH extracts with two different enzymes demonstrated that the non retted extract contained a relatively high molecular weight xylan not found in the retted extract. Treatment of the 1 M KOH extracts and the fibres with Endoglucanase V from Trichoderma viride demonstrated that while this enzyme solubilised cellulose as well as xylan and xyloglucan oligomers from the extract, it had limited access to these polymers on the fibre. MALDI-TOF MS analysis of the material solubilised from the extract suggested that the xylan was randomly substituted with 4-O-methyl glucuronic acid moieties. The xyloglucan was shown to be of the XXXG type and was substituted with galactose and fucose units. The enzyme treatments of the fibres demonstrated that the xylan and xyloglucan polymers in the fibres were not accessible to the enzyme but that material which was entrapped by the cellulose could be released by the hydrolysis of this cellulose.

Cellulase↗

Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin and Aspirin Reperfusion Therapy (HART II).

BACKGROUND: Adjunctive unfractionated heparin (UFH) during thrombolytic therapy for acute myocardial infarction (AMI) promotes the speed and magnitude of coronary artery recanalization and reduces reocclusion. Low-molecular-weight heparins offer practical and potential pharmacological advantages over UFH in multiple applications but have not been systematically studied as adjuncts to fibrinolysis in AMI. METHODS AND RESULTS: Four hundred patients undergoing reperfusion therapy with an accelerated recombinant tissue plasminogen activator regimen and aspirin for AMI were randomly assigned to receive adjunctive therapy for at least 3 days with either enoxaparin or UFH. The study was designed to show noninferiority of enoxaparin versus UFH with regard to infarct-related artery patency. Ninety minutes after starting therapy, patency rates (thrombolysis in myocardial infarction [TIMI] flow grade 2 or 3) were 80.1% and 75.1% in the enoxaparin and UFH groups, respectively. Reocclusion at 5 to 7 days from TIMI grade 2 or 3 to TIMI 0 or 1 flow and TIMI grade 3 to TIMI 0 or 1 flow, respectively, occurred in 5.9% and 3.1% of the enoxaparin group versus 9.8% and 9.1% in the UFH group. Adverse events occurred with similar frequency in both treatment groups. CONCLUSIONS: Enoxaparin was at least as effective as UFH as an adjunct to thrombolysis, with a trend toward higher recanalization rates and less reocclusion at 5 to 7 days.

Anticoagulants↗

Treatment of therapy-resistant perineal metastatic Crohn's disease after proctectomy using anti-tumor necrosis factor chimeric monoclonal antibody, cA2: report of two cases.

PURPOSE: Two young females with well-documented Crohn's disease and nonhealing perineal wounds following proctectomy compatible with "metastatic Crohn's disease" are described. We hypothesized that metastatic Crohn's disease would be a tumor necrosis factor-dependent inflammatory reaction and have treated these two patients with the anti-tumor necrosis factor chimeric monoclonal antibody, cA2. MAIN FINDINGS: Administration of cA2 was followed by a rapid reduction of subjective and objective parameters of inflammation and caused a substantial reduction of the wound size. CONCLUSION: These preliminary data are consistent with a tumor necrosis factor-dependent inflammatory cause of Crohn's disease and its extraintestinal manifestations and provide support for targeting tumor necrosis factor in this condition.

Adult↗

Carney's triad.

The purpose of this study is to provide an overview of cases of Carney's triad and to discuss the clinical implications of this diagnosis. A search was made of the English-language literature for original articles, reviews and abstracts addressing Carney's triad. A new patient was described and added to the number of known patients. In literature 40 patients were found with a complete or incomplete triad. There exists no agreement on the pathology and possible common origin of these tumours. Directions are given for diagnostics and therapy. The diagnosis of Carney's triad has specific clinical implications that make a good knowledge of this syndrome mandatory.

Adult↗

Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide.

Interactions between mononuclear cells are required for the formation of inflammatory infiltrates in the CNS and the activation of cellular effector functions provoking demyelination in MS. Membrane-expressed costimulatory molecules are crucial to such interactions. We therefore investigated whether two costimulatory molecules, CD40L (CD154, expressed on activated CD4-possible T cells) and selected CD44-variant isoforms (expressed on activated CD4-positive T cells), are targets for immunotherapy in MS. The model of experimental autoimmune encephalomyelitis (EAE) induced in SJL-mice by immunization with a peptide derived from the proteolipid protein (PLP139-151) was optimized to address these questions. A previous observation that anti-CD40L (CD154) monoclonal antibodies can effectively prevent EAE in this model was confirmed, and extended by demonstrating that CD40 is expressed by cells of the monocytic lineage infiltrating the spinal cord. In vivo treatment with antibody against the standard isoform of CD44 (CD44s or CD44H) did not affect disease burden. In contrast, combined treatment with antibodies against the isoforms CD44v6, v7 and v10, which are thought to be involved in inflammatory processes, reduced the disease burden considerably. In addition, CD44v10-expressing cells were detected in the spinal cord. These data support the idea that CD40-CD40L interactions form a target for immunotherapy of MS, and indicate that cells expressing CD44v6, v7 and/or v10-containing isoforms have such potential as well.

Animals↗

Sulfur tuft and turkey tail: biosynthesis and biodegradation of organohalogens by Basidiomycetes.

Chlorinated aliphatic and aromatic compounds are generally considered to be undesirable xenobiotic pollutants. However, the higher fungi, Basidiomycetes, have a widespread capacity for organohalogen biosynthesis. Adsorbable organic halogens (AOX) and/or low-molecular-weight halogenated compounds are produced by Basidiomycetes of 68 genera from 20 different families. Most of the 81 halogenated metabolites identified from Basidiomycetes to date are chlorinated, although brominated and iodated metabolites have also been described. Two broad categories of Basidiomycete organohalogen metabolites are the halogenated aromatic compounds and the haloaliphatic compounds. Some of these organohalogen metabolites have demonstrable physiological roles as antibiotics and as metabolites involved in lignin degradation. Basidiomycetes produce large amounts of low-molecular-weight organohalogens or adsorbable organic halogens (AOX) when grown on lignocellulosic substrates. In our view, Basidiomycetes, as decomposers of forest litter, are a major source of natural organohalogens in terrestrial environments. Basidiomycetes are also potent degraders of a wide range of chlorinated pollutants, such as bleachery effluent from kraft mills and pentachlorophenol, polychlorinated dioxins, and polychlorinated biphenyls. The extracellular, lignin-degrading enzymes of the Basidiomycetes are involved in the oxidative degradation of chlorophenols and dioxin and can cause reductive dechlorination of halomethanes. There is no clear-cut separation between "polluters" and "clean-uppers" within the Basidiomycetes. Several genera, e.g. Bjerkandera, Hericium, Phlebia, and Trametes, produce significant amounts of chlorinated compounds but are also highly effective in metabolizing or biotransforming chlorinated pollutants.

Anti-Bacterial Agents↗

Correlation between early recurrence and reoperation after ileocolonic resection in Crohn's disease: a prospective study.

BACKGROUND: The medical and surgical treatment of patients with Crohn's disease is directed at reducing symptoms and postponing recurrence. In the determination of high-risk groups for surgical recurrence after ileocolonic resection, the role of early endoscopic evaluation is unclear. STUDY DESIGN: We investigated the relationship between early recurrence detected endoscopically and recurrence detected by operation in a prospective study of 60 patients, who underwent ileocolonic resection for Crohn's disease. RESULTS: Recurrence detected endoscopically was found in 44 patients (73 percent) according to definition I (presence of any lesion detected endoscopically that was compatible with Crohn's disease) and in 21 patients (35 percent) according to definition II (five or more aphthous lesions present in the neoterminal ileum or at the anastomotic site, or 25 percent or more of the intestinal circumference inflamed). Recurrence detected surgically was found in 14 patients (23 percent). No correlation between early recurrence detected endoscopically and recurrence detected surgically was evident. CONCLUSIONS: Early recurrence detected endoscopically did not predict recurrence detected surgically.

Adolescent↗

Posterior sagittal anorectoplasty: functional results of primary and secondary operations in comparison to the pull-through method in anorectal malformations.

BACKGROUND: Control of defaecation after surgical correction of high and intermediate types of congenital anorectal malformations is difficult. The posterior sagittal approach with careful reconstruction of the external sphincter is postulated to give a better outcome than the pull-through operation. The functional results of these procedures performed in one centre were evaluated in order to identify prognostic factors. MATERIAL AND METHODS: Between 1979 and 1992 66 patients with high or intermediate congenital anorectal anomalies were treated in our centre. In 16 patients a pull-through operation (Kĩesewetter-Rehbein) was performed. After 1984, the posterior sagittal anorectoplasty (PSARP) (Peña and deVries) was used in 35 patients as the primary operation. In 22 patients a PSARP operation was done as a secondary procedure, in one third of these patients after a previous pull-through operation in our centre. The functional results were analysed in retrospect. RESULTS: Sixty operations in 53 patients could be evaluated. The overall continence rate was 34%. After the pull-through operation six out of 15 patients (40%) were continent, after a primary PSARP 10 out of 25 (40%) and after a secondary PSARP operation five out of 20 patients (25%). Patients with a sacral defect were continent only in 16% as compared to 44% of the patients with a normal sacrum. Sex was also relevant: 67% of the girls were continent, compared to 30% of the boys. Ten out of 11 girls (90%) with a normal sacrum became continent. CONCLUSION: The PSARP for high and intermediate anorectal malformations does not give better functional results than the pull-through operation. The prognosis is determined by other factors than the type of operation, notably sex and the presence or absence of sacral defects.

Anal Canal↗

Manganese regulation of veratryl alcohol in white rot fungi and its indirect effect on lignin peroxidase.

Many white rot fungi are able to produce de novo veratryl alcohol, which is known to be a cofactor involved in the degradation of lignin, lignin model compounds, and xenobiotic pollutants by lignin peroxidase (LiP). In this study, Mn nutrition was shown to strongly influence the endogenous veratryl alcohol levels in the culture fluids of N-deregulated and N-regulated white rot fungi Bjerkandera sp. strain BOS55 and Phanerochaete chrysosporium BKM-F-1767, respectively. Endogenous veratryl alcohol levels as high as 0.75 mM in Bjerkandera sp. strain BOS55 and 2.5 mM in P. chrysosporium were observed under Mn-deficient conditions. In contrast, veratryl alcohol production was dramatically decreased in cultures supplemented with 33 or 264 (mu)M Mn. The LiP titers, which were highest in Mn-deficient media, were shown to parallel the endogenous veratryl alcohol levels, indicating that these two parameters are related. When exogenous veratryl alcohol was added to Mn-sufficient media, high LiP titers were obtained. Consequently, we concluded that Mn does not regulate LiP expression directly. Instead, LiP titers are enhanced by the increased production of veratryl alcohol. The well-known role of veratryl alcohol in protecting LiP from inactivation by physiological levels of H(inf2)O(inf2) is postulated to be the major reason why LiP is apparently regulated by Mn. Provided that Mn was absent, LiP titers in Bjerkandera sp. strain BOS55 increased with enhanced fungal growth obtained by increasing the nutrient N concentration while veratryl alcohol levels were similar in both N-limited and N-sufficient conditions.

Journal Article↗

Significant biogenesis of chlorinated aromatics by fungi in natural environments.

Common wood- and forest litter-degrading fungi produce chlorinated anisyl metabolites. These compounds, which are structurally related to xenobiotic chloroaromatics, occur at high concentrations of approximately 75 mg of chlorinated anisyl metabolites kg of wood or litter in the environment. The widespread ability among common fungi to produce large amounts of chlorinated aromatic compounds in the environment makes us conclude that these kinds of compounds can no longer be considered to originate mainly from anthropogenic sources.

Journal Article↗

Physiological Role of Chlorinated Aryl Alcohols Biosynthesized De Novo by the White Rot Fungus Bjerkandera sp. Strain BOS55.

The white rot fungus Bjerkandera sp. strain BOS55 produces veratryl, anisyl, 3-chloroanisyl, and 3,5-dichloroanisyl alcohol and the corresponding aldehydes de novo from glucose. All metabolites are produced simultaneously with the extracellular ligninolytic enzymes and have an important physiological function in the fungal ligninolytic system. Both mono- and dichlorinated anisyl alcohols are distinctly better substrates for the extracellular aryl alcohol oxidases than veratryl alcohol. The aldehydes formed are readily recycled by reduction by washed fungal mycelium, thus creating an extracellular H(2)O(2) production system regulated by intracellular enzymes. Lignin peroxidase does not oxidize the chlorinated anisyl alcohols either in the absence or in the presence of veratryl alcohol. It was therefore concluded that the chlorinated anisyl alcohols are well protected against the fungus's own aggressive ligninolytic enzymes. The relative amounts of veratryl alcohol and the chlorinated anisyl alcohols differ significantly according to the growth conditions, indicating that production of veratryl alcohol and the production of the (chlorinated) anisyl metabolites are independently regulated. We conclude that the chlorinated anisyl metabolites biosynthesized by the white rot fungus Bjerkandera sp. strain BOS55 can be purposefully produced for ecologically significant processes such as lignin degradation.

Journal Article↗

[A mixed form of mucocele of the colon].

The term mucocele is applied to an accumulation of mucus within a lumen lined with mucus-secreting epithelium as well as to the structure resulting from leakage of mucus into surrounding connective tissue. The case report is presented of a patient with a bizarre, mixed type of mucocele after perforation of a hemicolon retained 26 years previously, a clinical picture which could not be traced in the literature.

Colonic Diseases↗

Stimulation of Ligninolytic Peroxidase Activity by Nitrogen Nutrients in the White Rot Fungus Bjerkandera sp. Strain BOS55.

Bjerkandera sp. strain BOS55, a newly isolated wild-type white rot fungus, produced lignin peroxidase (LiP) in nitrogen (N)-sufficient glucose-peptone medium, whereas no LiP was detectable in N-limited medium. The production of LiP was induced by the peptide-containing components of this medium and also by soy bean protein. Furthermore, the production of manganese-dependent peroxidase was stimulated by organic N sources, although lower production was also evident in N-limited medium. Further research showed that the induction of LiP depended on the combination of pH and the type of N source. An amino acid mixture and ammonium induced LiP only at either pH 6 or 7.3, respectively. Peptone induced LiP activity at all pH values tested; however, the highest activity was observed at pH 7.3. The results presented here indicate that Bjerkandera spp. are distinct from the model white rot fungus, Phanerochaete chrysosporium, which produces ligninolytic peroxidases in response to N limitation.

Journal Article↗

Purification and characterization of vanillyl-alcohol oxidase from Penicillium simplicissimum. A novel aromatic alcohol oxidase containing covalently bound FAD.

Vanillyl-alcohol oxidase was purified 32-fold from Penicillium simplicissimum, grown on veratryl alcohol as its sole source of carbon and energy. SDS/PAGE of the purified enzyme reveals a single fluorescent band of 65 kDa. Gel filtration and sedimentation-velocity experiments indicate that the purified enzyme exists in solution as an octamer, containing 1 molecule flavin/subunit. The covalently bound prosthetic group of the enzyme was identified as 8 alpha-(N3-histidyl)-FAD from pH-dependent fluorescence quenching (pKa = 4.85) and no decrease in fluorescence upon reduction with sodium borohydride. The enzyme shows a narrow substrate specificity, only vanillyl alcohol and 4-hydroxybenzyl alcohol are substrates for the enzyme. Cinnamyl alcohol is a strong competitive inhibitor of vanillyl-alcohol oxidation. The visible absorption spectrum of the oxidized enzyme shows maxima at 354 nm and 439 nm, and shoulders at 370, 417 and 461 nm. Under anaerobic conditions, the enzyme is easily reduced by vanillyl alcohol to the two-electron reduced form. Upon mixing with air, rapid reoxidation of the flavin occurs. Both with dithionite reduction and photoreduction in the presence of EDTA and 5-deazaflavin the red semiquinone flavin radical is transiently stabilized. Opposite to most flavoprotein oxidases, vanillyl-alcohol oxidase does not form a flavin N5-sulfite adduct. Photoreduction of the enzyme in the presence of the competitive inhibitor cinnamyl alcohol gives rise to a complete, irreversible bleaching of the flavin spectrum.

Alcohol Oxidoreductases↗