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Biomedical subjects

M Jansen

Publications and source records attributed to M Jansen.

At least 19 recordsLinked to original sources
PubMed2003

Sustained release of insulin from sodium hyaluronate based dry powder formulations after pulmonary delivery to beagle dogs.

Hyaluronic acid (HA) and recombinant human insulin were co-spray dried to form a dry powder suitable for inhalation (Mass Median Aerodynamic Diameter, MMAD=1 to 4 microm). Insulin systemic levels and corresponding glucose levels were monitored following administration of the microparticles to the lungs of male Beagle dogs. Release kinetics were modified by addition of excess zinc ions (Zn2+) or hydroxypropyl cellulose (HPC). HA formulations containing insulin (10%w/w) were found to extend the mean residence time (MRT) and terminal half-life (t(1/2)) when compared to spray dried pure insulin. Addition of Zn2+ also improved MRT (>9 fold), AUC/dose (2.5 fold) and Tmax (by a factor of 3) when compared to spray dried pure insulin. Addition of HPC improved MRT (>7 fold), AUC/dose (5 fold) and Tmax (by a factor of 3) when compared to spray dried pure insulin. Our results demonstrate the potential of HA-based dry powder drug delivery systems in the pulmonary controlled release of insulin.

Administration, Inhalation↗
PubMed2003

A novel specific bioassay for the determination of glucocorticoid bioavailability in human serum.

OBJECTIVE: Some patients develop side-effects even on relatively low doses of topically administered glucocorticoids (GCs), while others appear to be less sensitive to GCs. We have developed and validated a bioassay which can measure glucocorticoid bioavailability directly from small amounts of human serum to help elucidate underlying mechanisms. METHODS: We have stably transfected the human embryonic kidney cell line HEK293 with a plasmid expressing the glucocorticoid receptor, and a plasmid containing the luciferase gene preceded by three concatenated steroid response elements, bringing luciferase expression under control of the liganded glucocorticoid receptor. RESULTS: The assay, with an intra- and interassay coefficient of variance (CV) better than 10%, showed the expected difference in potency between different GCs (fluticasone propionate > budesonide > dexamethasone > hydrocortisone). No cross-reactivity was detected with other steroid hormones such as progesterone, testosterone and oestradiol. The bioassay easily detects the rise and subsequent fall of bioavailable GCs in human serum following ingestion of only 0.5 mg dexamethasone, and clearly reflects the diurnal cortisol rhythm. Moreover, systemic availability following inhalation of 2 x 250 micro g fluticasone propionate using a pressure dose inhaler could be demonstrated. CONCLUSIONS: This assay can be used to determine levels of bioavailable GCs in serum, both endogenous and administered, and thus may help in optimizing treatment regimens. The small amount of serum needed to perform an analysis makes this assay applicable even to infants.

Administration, Inhalation↗
PubMed2002

[HIV prevalence among injecting drug users in South Limburg, 1994-1998/1999: increasing trend in Heerlen, not in Maastricht].

OBJECTIVE: To determine the prevalence of HIV infection and gain insights into the risk behaviour among injecting drug users (IDU) in Heerlen and Maastricht, the Netherlands. DESIGN: Descriptive inventory. METHOD: In 1994, 1996 and 1998/1999 a questionnaire on risk behaviour was obtained from 866 IDUs in Heerlen and Maastricht, and 858 saliva and serum samples were also obtained for testing on HIV antibodies. RESULTS: In the total region of Heerlen and Maastricht, no significant change in HIV prevalence was found (1994: 10%, 1996: 12%, 1998/1999: 14%). However, in Heerlen the HIV prevalence was demonstrated to have increased significantly (1994: 11%, 1996: 16%, 1998/1999: 22%), whereas in Maastricht HIV prevalence was constant (1998/1999: 5%). The percentage of participants that injected drugs in the six months preceding the survey decreased from 80% in 1994 to 63% in 1998/1999. Injection-related risk behaviour slightly decreased: in 1998/1999 14% of the participants had borrowed used syringes or needles in the last 6 months. Additionally, inconsistent condom use with steady and casual sexual partners was reported. Of the participants, 86-89% did not always use condoms with steady partners and 49% with casual partners. DISCUSSION: In view of the increasing HIV prevalence among IDUs in Heerlen, the persistent injecting and sexual risk behaviour and the large number of IDUs who have sexual contact with non-users in Heerlen and Maastricht, there is a substantial risk of HIV transmission both within the IDU community and to the general population.

Adult↗
PubMed2002

Dilead mercury chromate(VI), Pb2HgCrO6.

The structure of Pb(2)HgCrO(6) (space group P-1) can be described as consisting of isolated [CrO(4)](2-) tetrahedra and nearly linear [HgO(2)](2-) dumb-bells, which form layers of composition [HgCrO(6)](4-). These are intercalated with corrugated pseudo-hexagonal Pb(2+) layers. The Pb(2+) cation is stereochemically active and has coordination 3+5.

Journal Article↗
PubMed2002

[Selective CT mesentericography in the diagnostics of obscure overt intestinal bleeding: preliminary results].

AIM: To evaluate intra-arterial CT mesentericography (CTM) in the diagnostics of severe obscure overt intestinal bleeding in comparison with conventional mesentericography (MG) and surgery. METHODS: In 8 patients (23 - 82 years, mean 59 years), CTM was performed via the catheter left in the superior mesenteric artery after MG to detect the source of bleeding. Early and late-phase spiral CT scans were acquired after administration of contrast medium. Active bleeding was considered to be present if extravasation of contrast medium into the bowel was found. The results of MG and CTM were compared with the results of surgery. RESULTS: With MG active bleeding was found in one patient, with CTM in five patients. In three patients, both MG and CTM were negative. Six patients underwent surgery. Five cases of bleeding detected with CTM were confirmed by surgery. In one case, bleeding found with CTM was not confirmed by surgery. One patient underwent surgery although all imaging procedures were negative. The source of bleeding remained unknown. Surgically, the site of bleeding was located in the jejunum in 3 patients (jejunitis, jejunal ulcers, carcinoid), one patient had a diverticulum in the ascending colon. The colonic bleeding site was correctly localized with CTM, whereas the small bowel bleeding could only roughly be assigned to the proximal or distal jejunum or jejunoileal transition area. CONCLUSION: Preliminary results indicate that selective CTM is superior to MG in the evaluation of severe obscure overt intestinal bleeding.

Adult↗
PubMed2002

The difficulty of height prediction in Weaver syndrome.

Accelerated growth and advanced bone age are consistent findings in Weaver-Smith syndrome (WSS). According to the rather scant reports in the literature, persons afflicted with WSS appear to achieve supranormal heights despite a significant bone age advancement in their growth period. The literature does not state clearly whether there is a discrepancy between bone age advancement and the time of onset of puberty in WSS. We report a girl with Weaver syndrome whose final height predictions were within normal limits according to the standard prediction models, who had to be eventually treated with high doses of estrogen in order to keep her final height within reasonable limits. We conclude that the pattern of growth and maturation in children with WSS may form an exception to the general rule that tall children with an advanced bone age mature early and thus attain a normal final height. A careful evaluation of growth data of other children with WSS is necessary to clarify this issue.

Abnormalities, Multiple↗
PubMed2002

Longitudinal analysis of growth and puberty in 21-hydroxylase deficiency patients.

AIMS: To evaluate growth from diagnosis until final height (FH) in 21-hydroxylase deficiency patients. METHODS: A retrospective longitudinal study was performed. Only patients treated with hydrocortisone and fludrocortisone (in case of salt wasting) were evaluated. This resulted in a sample of 34 (21 male, 13 female) salt wasting patients (SW) and 26 (13 male, 13 female) non-salt wasting patients (NSW). Auxological data were compared to recent Dutch reference values. RESULTS: In the first three months of life, the mean length SDS decreased to -1.50, probably because of the high average glucocorticoid dose (40 mg/m2/day). FH corrected for target height (FH(corr)TH) was -1.25 and -1.27 SDS in females and males, respectively. Patients treated with salt supplements during the first year, had a better FH(corr)TH (-0.83 SDS). In NSW patients, FH(corr)TH was -0.96 and -1.51 SDS in females and males, respectively. In SW and NSW, age at onset of puberty was within normal limits, but bone age was advanced. Mean pubertal height gain was reduced in males. Body mass index was only increased in NSW females. CONCLUSION: In SW, loss of final height potential might be a result of glucocorticoid excess in the first three months and sodium depletion during infancy. In NSW, loss of FH potential was caused by the delay in diagnosis. In SW and NSW, the advanced bone age at onset of puberty (undertreatment in prebertal years) resulted in loss of height gain during puberty. The effect of intensive sodium chloride support in early infancy should be examined prospectively. Neonatal screening is required if the height prognosis in NSW patients is to be improved.

Adrenal Hyperplasia, Congenital↗
PubMed2002

Fcgamma receptor IIa, IIIa, and IIIb polymorphisms in German patients with systemic lupus erythematosus: association with clinical symptoms.

BACKGROUND: Receptors for IgG play an important part in immune complex clearance. Several studies have identified polymorphisms of receptors for the Fc fragment of IgG (FcgammaR) as genetic factors influencing susceptibility to disease or disease course of systemic lupus erythematosus (SLE). OBJECTIVE: To examine these possibilities by evaluating a panel of clinical parameters in a cohort of 140 German patients with SLE for correlations with the FcgammaRIIa, IIIa, and IIIb polymorphisms in an explorative study. METHODS: 140 German patients with SLE according to American College of Rheumatology (ACR) criteria and 187 German controls were genotyped for the FcgammaRIIa, IIIa, and IIIb polymorphisms. Associations between FcgammaR genotypes, combined genotypes and clinical as well as laboratory features were analysed. RESULTS: No significant skewing of any of the three FcgammaR polymorphisms was seen in the German SLE cohort studied. Various clinical and serological parameters were found more frequently and at younger age in homozygous patients with the genotypes IIA-R/R131 or IIIA-F/F158 than in patients with IIA-H/H131 or IIIA-V/V158. These effects were even more pronounced in patients with the low binding combined phenotypes of the FcgammaRIIa, IIIa (double negative phenotypes) and FcgammaRIIa, IIIa, and IIIb (triple negative phenotypes). In patients with the double negative IIA and IIIA genotypes significantly higher frequencies of nephritis (63% v 33%) and proteinuria according to ACR criteria (58% v 11%), anaemia (84% v 55%), and anticardiolipin antibodies (63% v 22%) were found than in patients with the double positive genotypes. Patients with the IIA-R/R131 genotype and the double negative homozygous genotype had an earlier incidence of clinical symptoms, haematological and immunological abnormalities. Accordingly, SLE is diagnosed earlier in these patients, the difference reaching statistical significance only in the double negative v the double positive genotype (26.3 v 39.5 years) and the IIIA-F/F158 genotype v the rest (26.7 v 32.0 years). Most relevant is the fact that a higher median disease activity (ECLAM score) was demonstrated, both in the IIA-R/R131 homozygous (3.3 v 2.7) and the double negative (3.4 v 2.3) patients, reaching statistical significance in the first group. CONCLUSION: The results of this explorative study support the view that the FcgammaRIIa/IIIa and IIIb polymorphisms constitute factors influencing clinical manifestations and the disease course of SLE but do not represent genetic risk factors for the occurrence of SLE. Higher frequencies of clinical symptoms, haematological and immunological abnormalities as well as an earlier onset of clinical symptoms, haematological and immunological markers of active disease were found in patients with the IIA-R/R131 genotype and the double negative and triple negative genotypes.

Adolescent↗
PubMed2002

The LDH ratio as a marker for response to plasma exchange in HUS/TTP of the adult.

BACKGROUND: Plasma exchange improved the outcome of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) of the adult markedly, but a high number of non-responders remain. Identifying these patients at an early stage would help to optimize therapy. AIM: determine the value of serologic measures in predicting the response to plasma exchange. MATERIAL AND METHODS: We performed a retrospective chart review of 30 patients with HUS/TTP of the adult treated with plasma exchange. According to the treatment protocol, a mean of 42 +/- 8.2 ml plasma per kilogram of body weight was exchanged daily for 3 days and continued every second day thereafter. Prior to each session, clinical status and serologic markers for hemolysis and kidney function were obtained. To assess the early individual response to plasma exchange, the decline of LDH from the first to the third cycle was calculated as: LDH concentration before the third session/LDH concentration before the first session (LDH ratio). RESULTS: During the observation period (median 195, range 6-1500 days), 80% of the patients responded to therapy with plasmapheresis. None of the serologic measures or clinical signs obtained before initiation of plasma exchange showed a significant correlation with the outcome. After 2 sessions of plasma exchange, only LDH and platelet level had improved markedly in responding patients. The LDH ratio was the best predictive marker for the individual response. An LDH ratio < 0.6 predicted a favorable outcome with a sensitivity of 0.96 and a specificity of 0.83. CONCLUSION: The LDH ratio might be a useful marker for separating patients responding to plasma exchange from those not responding at an early stage.

Adult↗
PubMed2002

Non-myeloablative allogeneic stem cell transplantation in patients with solid tumours and patients with a haematological malignancy.

Allogeneic stem cell transplantation (allo-SCT) is a treatment option for several haematological tumours, not only to regain haematopoiesis after myeloablative chemotherapy and/or radiotherapy, but also for its apparent antitumour effect. This so-called graft-versus-tumour effect might not only be effective against haematological tumours, where it has best been proven, but also against solid tumours. To reduce morbidity and treatment-related mortality of allo-SCT, efforts are being made to establish engraftment of allogeneic stem cells after a non-myeloablative conditioning regimen and create a 'mini transplantation'. Such a therapy relies more heavily on the graft-versus-malignancy effect than on the antitumour effect exerted by the chemotherapy/radiotherapy. Here, we report the outcomes of 15 patients with haematological disease or solid tumours who underwent an SCT in the University Hospital Maastricht after a non-myeloablative fludarabine/cyclophosphamide conditioning regimen. Although results are promising, adjustments will be needed to ensure long-term stable engraftment and optimise the antitumour effect.

Adult↗
PubMed2001

Structure of the fluorosulfite anion: rotational disorder of SO(2)F(-) in the alkali metal fluorosulfites and crystal structures of alpha- and beta-CsSO(2)F.

19F solid-state NMR spectra of the alkali metal fluorosulfites KSO(2)F, RbSO(2)F, alpha-CsSO(2)F, and beta-CsSO(2)F show that the fluorosulfite anion is subjected to dynamical disorder at room temperature. This disorder can be modeled by 120 degrees rotational jumps with respect to the C(3)-pseudoaxis of the anion. The exchange frequency of this disorder decreases with decreasing temperature. The calculated jump frequencies at room temperature are 5 x 10(5) Hz for KSO(2)F, 2 x 10(5) Hz for RbSO(2)F, 1 x 10(7) Hz for alpha-CsSO(2)F, and 5 x 10(5) Hz for beta-CsSO(2)F, respectively. The crystal structures of alpha- and beta-CsSO(2)F were determined for the first time (alpha: Pnma; Z = 4; a = 790.98(8), b = 666.07(7), c = 798.93(9) pm; T = 293 K. beta: R3m; Z = 3; a = 659.22(6), c = 800.50(4) pm; T = 293 K). X-ray single-crystal data of KSO(2)F, RbSO(2)F, and alpha-CsSO(2)F taken at various temperatures were refined using the disorder model developed from the NMR results. It is shown that it is impossible to obtain reliable structural parameters of the SO(2)F(-) ion by refinement of X-ray data as long as rotational disorder persists. The preference of an ordered structure increases with decreasing temperature. The degree of disorder remaining in alpha-CsSO(2)F at 93 K is small. The structural parameters of the fluorosulfite anion as obtained by a routine refinement of this phase (S-F, 169.0(2) pm; S-O, 147.8(1) pm) are the best lower (S-F) and upper (S-O) limits of the "true" bond lengths determined experimentally. They comply with the values obtained from quantum chemical calculations.

Journal Article↗
PubMed2001

[Lump in the neck: 4 patients with a medullary thyroid carcinoma].

In a 25-year-old man, medullary thyroid carcinoma (probably a solitary sporadic form) was diagnosed following investigation of a small lump in the patient's neck. This was removed and followed up with further treatment. In a 27-year-old man, episodes of headache, palpitations and excessive perspiration (due to a pheochromocytoma) and a positive family history of thyroid problems led to further investigations and the subsequent diagnosis of multiple endocrine neoplasia (MEN) type 2A. The patient died at 48 years of age as the result of liver metastases. A total thyroidectomy had been carried out on a 19-year-old man with familial medullary thyroid carcinoma. The calcitonin levels remained elevated, but no tumour residues could be found. A 16-year-old girl with MEN type 2B had also previously undergone surgery. Her main complaint consisted of persistent constipation. Thyroid carcinomas usually present as a nodule in the neck. In 25% of cases, medullary thyroid carcinoma is part of the MEN2 syndrome. The clinical approach for medullary thyroid carcinoma is based on pathological findings following fine needle aspiration biopsy. The results of DNA tests determine the course of treatment and the need for family testing. In families with a hereditary form, there is a clear genotype-phenotype correlation. Early diagnosis and treatment can improve life expectancy.

Adolescent↗
PubMed2001

Al(22)Cl(20).12L (L = THF, THP): the first polyhedral aluminum chlorides.

Aluminum subhalides of the type Al(22)X(20).12L (X = Cl, Br; L = THF, THP) are the only known representatives of polyhedral aluminum subhalides and exhibit interesting multicenter bonding properties. Herein, we report on the synthesis and structural investigation of the first chlorides of this type. Additional investigations applying solid-state (27)Al NMR (MAS), XPS (of Al(4)Cp(4) and Al(22)X(20).12L), and quantum chemical calculations shed more light upon the structure of the molecules and possible Al modifications.

Journal Article↗
PubMed2001

Activity of human IgG and IgA subclasses in immune defense against Neisseria meningitidis serogroup B.

Both IgG and IgA Abs have been implicated in host defense against bacterial infections, although their relative contributions remain unclear. We generated a unique panel of human chimeric Abs of all human IgG and IgA subclasses with identical V genes against porin A, a major subcapsular protein Ag of Neisseria meningitidis and a vaccine candidate. Chimeric Abs were produced in baby hamster kidney cells, and IgA-producing clones were cotransfected with human J chain and/or human secretory component. Although IgG (isotypes IgG1-3) mediated efficient complement-dependent lysis, IgA was unable to. However, IgA proved equally active to IgG in stimulating polymorphonuclear leukocyte respiratory burst. Remarkably, although porin-specific monomeric, dimeric, and polymeric IgA triggered efficient phagocytosis, secretory IgA did not. These studies reveal unique and nonoverlapping roles for IgG and IgA Abs in defense against meningococcal infections.

Animals↗
PubMed2001

Mono-N-carboxymethyl chitosan (MCC), a polyampholytic chitosan derivative, enhances the intestinal absorption of low molecular weight heparin across intestinal epithelia in vitro and in vivo.

The synthesis and evaluation of mono-N-carboxymethyl chitosan (MCC) as an intestinal permeation enhancer for macromolecular therapeutics is presented. MCCs were synthesized from two different viscosity grade chitosans to yield both high and low viscosity grade products. These MCCs were tested on Caco-2 cells for their efficiency to decrease the transepithelial electrical resistance (TEER) and to increase the paracellular permeability of the anionic macromolecular anticoagulant low molecular weight heparin (LMWH). For in vivo studies, LMWH was administered intraduodenally with or without MCC to rats. Both types of experiments were performed at pH 7.4. Results show that both viscosity grade MCCs managed to significantly decrease the TEER of Caco-2 cell monolayers when they were applied apically at concentrations of 3-5% (w/v). Transport studies with Caco-2 cells revealed substantial increases of LMWH permeation in the presence of both viscosity grade MCCs compared with controls. In rats, 3% (w/v) low viscosity MCC significantly increased the intestinal absorption of LMWH, reaching the therapeutic anticoagulant blood levels of LMWH. Both in vitro and in vivo results indicate that the polyampholytic chitosan modification MCC is a suitable and functional polymer for the delivery and intestinal absorption of anionic macromolecular therapeutics like LMWH.

Animals↗
PubMed2001

[Prognostic factors for development of peritoneal carcinosis in stomach carcinoma].

OBJECTIVE: Several adjuvant therapy concepts have been developed to improve the treatment of gastric cancer patients. Dealing with intraperitoneal chemotherapy, it seems to be useful to determine suitable prognostic factors for the occurrence of peritoneal carcinosis, as it is possible to select patients who may profit from this therapy. METHODS: Between June 1975 and December 1999 resection of gastric cancer was performed in 575 patients. From 1 January 1986 clinical data were recorded prospectively, before that time, retrospectively. The complete data concerning preoperative diagnosis, operation, histology, postoperative course and survival time were documented in an Excel file for statistical analysis. Multivariate analysis was performed using the chi-squared logistic regression test. RESULTS: Significant correlation was found between the occurrence of peritoneal dissemination and tumour stage pT3, pN2, G3, cancer of the whole stomach and cancer at the anastomotic site after partial gastric resection. Lauren classification, signet-ring cell cancer, liver metastasis and tumour localisation in the distal or proximal stomach showed no significant correlation to peritoneal carcinosis in the multivariate analysis. However, only one-third of patients with liver metastasis had simultaneous peritoneal dissemination. CONCLUSION: The results show a clinical correlation of tumour localisation, infiltration of the serosa, lymph node metastasis and grading with peritoneal dissemination. The present data serve as a basis for further histochemical and molecular biological investigations e.g. of the expression of adhesion molecules to determine the risk of peritoneal tumour dissemination after gastric cancer.

Adult↗