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Biomedical subjects

H Nielsen

Publications and source records attributed to H Nielsen.

At least 37 records · Page 2Linked to original sources
PubMed2002

Preoperative routine magnetic resonance cholangiopancreatography before laparoscopic cholecystectomy: a prospective study.

OBJECTIVES: To assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) in detecting common bile duct stones in the preoperative investigation of patients electively referred for gallstone disease, to find out the incidence of asymptomatic common duct stones, and to correlate clinical symptoms and history and liver function tests (LFT) with the actual occurrence of common duct stones. DESIGN: Prospective study. SETTING: General hospital, Denmark. PATIENTS: 180 consecutive non-jaundiced patients referred with symptomatic gallstones for elective cholecystectomy. INTERVENTIONS: LFT, abdominal ultrasonography, MRCP, endoscopic retrograde cholangiopancreatography (ERCP), questionnaire. MAIN OUTCOME MEASURES: Positive and negative predictive values and accuracy of MRCP, number of patients with asymptomatic stones, and correlation of symptoms with the presence of stones. RESULTS: 26/180 patients had common duct stones (14%). Only one (<1%) had an asymptomatic stone. For detection of such stones, MRCP's positive predictive value was 0.95 (95% confidence interval (CI): 0.86 to 1.00), negative predictive value 0.96 (0.93 to 0.99), and accuracy 0.85 (0.93 to 0.99). MRCP missed 5 stones 1-4 mm in size in 5 patients; 17/64 patients with raised LFTs had stones (27%). The probability of stones was highest when the patients had both raised LFTs and a dilated common (>7 mm) bile duct (82%). There were no readmissions with ductal stones in the 6-month postoperative period. CONCLUSIONS: The predicive values of MRCP were fairly good, but MRCP misses some small stones <5 mm in size. Asymptomatic stones in the common duct are not common in this population and should not be screened for. The probability of stones increases with the number of predictive factors. Patients should be questioned carefully about signs of biliary obstruction, and only be offered preoperative MRCP should they have a suspicious history, raised LFTs, or a dilated common duct.

Adult↗
PubMed2001

Effect of secondary structure on the thermodynamics and kinetics of PNA hybridization to DNA hairpins.

The binding of a series of PNA and DNA probes to a group of unusually stable DNA hairpins of the tetraloop motif has been observed using absorbance hypochromicity (ABS), circular dichroism (CD), and a colorimetric assay for PNA/DNA duplex detection. These results indicate that both stable PNA-DNA and DNA-DNA duplexes can be formed with these target hairpins, even when the melting temperatures for the resulting duplexes are up to 50 degrees C lower than that of the hairpin target. Both hairpin/single-stranded and hairpin/hairpin interactions are considered in the scope of these studies. Secondary structures in both target and probe molecules are shown to depress the melting temperatures and free energies of the probe-target duplexes. Kinetic analysis of hybridization yields reaction rates that are up to 160-fold slower than hybridization between two unstructured strands. The thermodynamic and kinetic obstacles to hybridization imposed by both target and probe secondary structure are significant concerns for the continued development of antisense agents and especially diagnostic probes.

Circular Dichroism↗
PubMed2001

The tumor-infiltrating B cell response in medullary breast cancer is oligoclonal and directed against the autoantigen actin exposed on the surface of apoptotic cancer cells.

Medullary carcinoma of the breast (MCB) is a morphologically and biologically distinct subtype of human breast cancer that, despite cytologically anaplastic features, has a more favorable prognosis than other types of breast cancer at similar stages of differentiation. It has been proposed that the improved clinical outcome is due, at least in part, to the presence of a prominent lymphoplasmacytic cell infiltrate in the tumor stroma. We studied the B lymphoplasmacytic cell infiltrates in MCB to determine the role of the antibody response produced by the local infiltrating cells. Oligoclonal predominance among tumor-infiltrating B cells in a panel of MCB patients was observed, suggesting that certain B cell clones were expanded, possibly in response to specific tumor-associated stimuli. IgG antibody phage-display libraries were generated from MCB-infiltrating lymphoplasmacytic cells of two patients, and MCB-reactive monoclonal antibodies were retrieved by selection on fresh-frozen MCB tissue sections. Analysis by mass spectrometry revealed that the antigen targeted by the dominant clones in the oligoclonal B lymphoplasmacytic response in both patients was not a cancer-specific antigen but the cytoskeletal protein beta-actin. MCB exhibits an increased rate of apoptosis, and apoptotic MCB cells were shown to expose actin on the cell surface, permitting its recognition by the humoral immune system. Further, actin fragments, similar to those observed after cleavage with the apoptotic protease granzyme B, were observed in MCB tissue. Our results indicate that the major antibody response produced by tumor-infiltrating B lymphoplasmacytic cells are autoimmune in nature and a consequence of the perturbed state of increased MCB apoptosis caused by granzyme B-induced T cell cytotoxicity and/or intrinsic cellular factors of MCB cells.

Actins↗
PubMed2001

Risk of dementia in Parkinson's disease: a community-based, prospective study.

OBJECTIVE: To calculate the incidence of and determine possible risk factors for dementia in PD. BACKGROUND: Dementia has important clinical consequences for patients with PD and their caregivers, but the incidence is unknown. METHODS: A population-based cohort of nondemented patients with PD (n = 171) from the county of Rogaland, Norway, was assessed at baseline and 4.2 years later with a comprehensive evaluation of motor, cognitive, and neuropsychiatric symptoms. The diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised (DSM-III-R) criteria, based on interview of the patient and a caregiver, cognitive rating scales, and neuropsychologic tests. A representative sample of 3,062 nondemented elderly subjects without PD served as control group. RESULTS: Forty-three patients with PD were demented at follow-up evaluation, equivalent to an incidence rate of 95.3 per 1,000 person-years (95% CI, 68.2 to 122.0). The risk for the development of dementia in patients with PD relative to the control subjects after adjusting for age, sex, and education was 5.9 (95% CI, 3.9 to 9.1). Predictive factors at baseline for dementia in PD in addition to age were Hoehn & Yahr score >2 (OR, 3.4; 95% CI, 1.3 to 8.6) and Mini-Mental State Examination score < 29 (OR, 3.3; 95% CI, 1.3 to 8.2). CONCLUSIONS: Patients with PD have an almost sixfold increased risk for becoming demented compared with subjects without PD.

Aged↗
PubMed2001

MRI of the arthritic small joints: comparison of extremity MRI (0.2 T) vs high-field MRI (1.5 T).

The aim of this study was to compare the diagnostic capabilities of extremity MRI (E-MRI) with high-field MRI in arthritic small joints, and to evaluate the patients' acceptance and perceptions of the two MR systems. One hundred three patients (group 1 = 28 patients with RA < 3 years, group 2 = 25 patients with reactive and psoriatic arthritis and mixed connective tissue disease, group 3 = 25 patients with rheumatoid arthritis (RA) more than 3 years and group 4 = 25 patients with arthralgia) underwent dedicated E-MRI and high-field MRI of the wrist and finger joints. Coronal short tau inversion recovery and transversal 3D T1-weighted images before and after gadodiamide (Gd) were performed in both cases to outline the volume of the synovial membrane (Vsm) and to evaluate joints with enhancement, effusion, bone edema, and erosions. Investigators blinded to the clinical findings evaluated the images. Patients' compliance and acceptance of E-MRI and high-field MRI were evaluated. The median Vsm obtained on E-MRI did not differ significantly from that obtained on high-field MRI. Vsm = 1 ml (E-MRI) and 1.1 ml (high-field MRI) before Gd and Vsm = 0.1 ml (E-MRI) and 0 ml (high-field MRI) after Gd (Wilcoxon test, p > 0.05). The difference in agreement was 8% for joint enhancement, 2% for joint effusion, 3% for bone edema, and 4% for bone erosions. Of the patients, 64% preferred E-MRI due to more comfortable positioning and less claustrophobia and noise. Extremity MRI of the small arthritic joints is comparable to high-field MRI and more readily accepted than high-field MRI by this patient group.

Adult↗
PubMed2001

Subtype-specific problems with qualitative Amplicor HIV-1 DNA PCR test.

BACKGROUND: commercial HIV-1 qualitative DNA PCR tests have the potential to detect virus in patients in whom antibody tests may be ineffective, such as patients with primary HIV infection and infants born to HIV seropositive mothers. However, the genetic diversity of HIV-1 raises concern about the ability of the PCR tests to detect all current subtypes. OBJECTIVES: to asses the sensitivity of the Amplicor HIV-1 test on 126 whole-blood samples representing seven different subtypes and to investigate the sensitivity when the standard assay was modified by including the primer pair SK145 and SKCC1B. RESULTS: of the 126 HIV-1 infected persons, 113 were tested positive and 13 were DNA PCR negative. On the basis of these results, the standard Amplicor HIV-1 test had a sensitivity of 90% in our cohort. In addition, 9% of the positive samples showed a low reactivity but above the cut-off of the assay. The standard assay yielded sensitivities of 100% for subtype B (n=16), D (n=9) and G (n=1), but only 83% for subtype A (n=41), 98% for subtype C (n=43), 79% for subtype E (n=14) and 0% for subtype F (n=2). All samples with low reactivity were non-B subtype. Eight of the DNA PCR negative samples, four subtype A, one C and three E were amplified with the modified Amplicor HIV-1 test with addition of SK145/SKCC1B primers. Using this modified protocol, six samples out of eight became positive. However, two samples (one A and one C) remained DNA PCR negative. CONCLUSION: this study confirms that the Amplicor HIV-1 test does not detect all subtypes with equivalent sensitivity and 10% of the samples, tested negative. Thus, it is preferable to add the SK145/SKCC1B primers to the standard test, where infection with non-B subtype is suspected.

DNA, Viral↗
PubMed2001

Family-based transmission disequilibrium test (TDT) and case-control association studies reveal surfactant protein A (SP-A) susceptibility alleles for respiratory distress syndrome (RDS) and possible race differences.

A key cause of respiratory distress syndrome (RDS) in the prematurely born infant is deficiency of pulmonary surfactant, a lipoprotein complex. Both low levels of surfactant protein A (SP-A) and SP-A alleles have been associated with RDS. Using the candidate gene approach, we performed family-based linkage studies to discern linkage of SP-A to RDS and identify SP-A susceptibility or protective alleles. Moreover, we performed case-control studies of whites and blacks to detect association between RDS and SP-A alleles. Transmission disequilibrium test (TDT) analysis revealed that the frequency of transmission (from parent to the offspring with RDS) of alleles 6A(2) and 1A(0) and of 1A(0)/6A(2) haplotype in RDS was increased, whereas transmission of alleles 1A(5) and 6A(4) and of haplotype 1A(5)/6A(4) was decreased. Extended TDT analysis further strengthened the observations made. The case-control studies showed that in whites or blacks with RDS the frequencies of specific genotypes, 1A(0) and 6A(2) or 1A(0), were increased, respectively, but the frequency of specific 6A(3) genotypes was increased in certain white subgroups and decreased in blacks. Regression analysis revealed gestational age (GA) and 6A(3) genotypes are significant factors in blacks with RDS. In whites with RDS, GA and antenatal steroids are important factors. The data together indicate linkage between SP-A and RDS; certain SP-A alleles/haplotypes are susceptibility (1A(0), 6A(2), 1A(0)/6A(2)) or protective (1A(5), 6A(4), 1A(5)/6A(4)) factors for RDS. Some differences between blacks and whites with regard to SP-A alleles may exist.

Alleles↗
PubMed2001

Inflammatory activation of neutrophils by Helicobacter pylori; a mechanism insensitive to pertussis toxin.

Chronic active gastritis of the antral mucosa is a characteristic feature of infection with Helicobacter pylori and interactions between bacterial components and inflammatory cells are believed to play an important pathogenic role. Neutrophils stimulated with H. pylori sonicate were demonstrated to release L-selectin (CD62L) expressed on the cellular surface, with a subsequent up-regulation of the beta2-integrins CD11b and CD11c, both in a dose- and time-dependent manner, reaching maximum levels after 45-60 min of stimulation. No changes were observed for the CD11a receptor upon stimulation. The activating properties of H. pylori sonicates on neutrophils were heat-labile and susceptible to protease attack, indicating the protein nature of the activating factor. After size fractionation, the major neutrophil-inducing activity was detected in the high molecular weight fraction exhibiting urease activity. Pertussis toxin was unable to inhibit neutrophil activation by the H. pylori protein(s). We conclude that proteins from H. pylori have a potent inflammatory effect on the surface membrane molecules CD62L, CD11b and CD11c essential for transendothelial migration of neutrophils to areas of inflammation. The neutrophil-activating protein(s) act via a pertussis toxin-insensitive mechanism.

CD18 Antigens↗
PubMed2001

Low body weight and type of protease inhibitor predict discontinuation and treatment-limiting adverse drug reactions among HIV-infected patients starting a protease inhibitor regimen: consistent results from a randomized trial and an observational cohort.

OBJECTIVES: To assess predictors for discontinuation and treatment-limiting adverse drug reactions (TLADR) among patients starting their first protease inhibitor (PI). METHODS: Data on patients starting a PI regimen (indinavir, ritonavir, ritonavir/saquinavir and saquinavir hard gel) in a randomized trial (RAS, n = 318) and an observational cohort (OBC, n = 505) were used to document reasons for discontinuation and TLADR. Risk factors for discontinuation of the initial PI/developing TLADR were assessed in Cox models. RESULTS: A total of 43 (RAS) and 48% (OBC) discontinued the initial PI therapy within less than 2 years. In both populations TLADR were the most common reason for discontinuation. The incidence of TLADR in RAS was: 8.5 (indinavir), 66.0 (ritonavir), 15.6 (saquinavir hard gel) per 100 person-years of follow-up (P < 0.001). Body weight and type of PI initiated were independent risk factors for treatment discontinuation and TLADR in both groups. In OBC, the risk of developing TLADR increased by 12% per 5 kg lower body weight when starting the PI regimen [the relative hazard (RH) was 1.12 (95% confidence interval: 1.05-1.19) per 5 kg lighter], and starting ritonavir was associated with a three- to sixfold higher risk of TLADR relative to other PI regimens. Very similar results were documented in RAS [RH for body weight was 1.18 (1.07-1.29)]. CONCLUSIONS: Nearly half of the patients stopped treatment with the initial PI, most commonly as a result of adverse drug reactions. Low body weight and initiation of ritonavir relative to other PIs were associated with an increased risk of TLADRs. Very consistent results were found in a randomized trial and an observational cohort.

Adult↗
PubMed2001

HIV-1 subtypes in Denmark.

The objective of this study was to investigate the presence of non-subtype B HIV-1 in Denmark. The C2-V3-C3 region of the env gene from proviral DNA obtained from patients suspected of being infected with non-subtype B virus was PCR-amplified and directly sequenced. The DNA sequences were aligned with full-length HIV-1 reference strains from each subtype and analysed using the phylogenetic package PHYLIP 3.1. The neighbour-joining method was used with 100 bootstraps. Of the 144 patients included in this study C2-V3-C3 sequences were obtained from 129 patients (90%). The phylogenetic analyses showed that virus from 49 patients (38%) was subtype A, 39 (30%) subtype C, 9 (7%) subtype D, 14 (11%) subtype CRF01_AE, 16 (12%) subtype B, 1 (1%) subtype F and 1 (1%) subtype J. This study demonstrates that almost all subtypes can be detected in Denmark; all non-subtype B infections could be traced to countries with a high prevalence of non-subtype B virus.

DNA, Viral↗
PubMed2001

Fetuin and fetuin messenger RNA in granulosa cells of the rat ovary.

The hardening reaction that occurs in the zona pellucida to block polyspermy can be overcome in oocyte cultures in the presence of fetal serum or the serum component fetuin. Fetuin may also prevent precocious zona hardening by inhibiting a ZP2 proteinase released spontaneously by cortical granules during maturation of the oocyte. We demonstrated fetuin mRNA in the rat ovary by reverse transcriptase-polymerase chain reaction and localized it by in situ hybridization. Fetuin mRNA was present in all granulosa cells of growing and large follicles. Immunohistochemical analysis revealed that the fetuin protein was only present in some of the small, growing follicles. In large, healthy follicles, fetuin protein was confined to cumulus cells and granulosa cells bordering the antrum. Fetuin was present in atretic follicles, but the staining pattern differed from that of healthy follicles. The follicular antrum contained a substantial amount of fetuin, but whether granulosa cells secreted it or it originated in the ovarian blood supply could not be confirmed. We concluded that at least a portion of the fetuin is produced by granulosa cells of growing and large follicles, suggesting that fetuin may function in a paracrine manner to maintain the zona pellucida in a penetrable state for fertilization.

Animals↗
PubMed2001

Helicobacter felis does not stimulate human neutrophil oxidative burst in contrast to 'Gastrospirillum hominis' and Helicobacter pylori.

Helicobacter pylori is a human pathogen, whereas the natural hosts for 'Gastrospirillum hominis' and Helicobacter felis are animals. 'G. hominis' is occasionally found to cause infection in humans, whereas H. felis only rarely infects humans. The pathogenesis of H. pylori infection is not completely understood and in order to reveal differences in immune response to the three Helicobacter species, the upregulation of adherence molecule CD11b/CD18, chemotactic activity and oxidative burst response of neutrophils after stimulation with H. pylori, 'G. hominis' and H. felis sonicates, were compared. Like H. pylori, 'G. hominis' and H. felis induced upregulation of CD11b/CD18 and chemotaxis of neutrophils. 'G. hominis' demonstrated a more pronounced upregulation of CD11b/CD18, whereas H. felis was the strongest stimulant of neutrophil chemotaxis. H. felis was unable to stimulate neutrophils to oxidative burst response, whereas 'G. hominis' activated neutrophils in a dose-dependent way similar to H. pylori. 'G. hominis' and H. felis were both able to prime neutrophils for oxidative burst response similar to H. pylori. In conclusion, we observed clear differences in neutrophil responses to different Helicobacter species, which indicates that bacterial virulence factors may be important for the diversity in the pathogenetic outcome of Helicobacter infections.

Bacterial Proteins↗
PubMed2001

European multicentre study to define disease activity criteria for systemic sclerosis. I. Clinical and epidemiological features of 290 patients from 19 centres.

OBJECTIVE: To investigate the existence of differences among European referral centres for systemic sclerosis (SSc) in the pattern of attendance and referral and in the clinical and therapeutical approaches. METHODS: In 1995 the European Scleroderma Study Group initiated a multicentre prospective one year study whose aim was to define the disease activity criteria in SSc. During the study period each participating European centre was asked to enroll consecutive patients satisfying American College of Rheumatology criteria for SSc and to fill out for each of them a standardised clinical chart. Patients from various centres were compared and differences in epidemiological, clinical, and therapeutical aspects were analysed. RESULTS: Nineteen different medical research centres consecutively recruited 290 patients. The patients could be divided into two subgroups: 173 with the limited (lSSc) and 117 with the diffuse (dSSc) form of the disease. The clinical and serological findings for the series of 290 patients seemed to be similar to data previously reported. However, when the data were analysed to elicit any differences between the participating centres, a high degree of variability emerged, in both epidemiological and clinical features and in the diagnostic and therapeutic approaches to the disease. CONCLUSIONS: The clinical approach to SSc, not only in different countries but also in different centres within the same country, is not yet standardised. To overcome this problem, it will be necessary for the scientific community to draw up a standardised procedure for the management of patients with SSc. This would provide a common research tool for different centres engaged in research on this complex disease.

Adolescent↗
PubMed2001

European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes.

OBJECTIVE: To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use. METHODS: Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0-10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity ("inactive to moderately active" or "active to very active" disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed. RESULTS: A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Delta-factors-that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Delta-cardiopulmonary (4.0), Delta-skin (3.0), Delta-vascular (2.0), and Delta-articular/muscular (1.0) for patients with dSSc; (b) Delta-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Delta-cardiopulmonary (1.5), Delta-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Delta-cardiopulmonary (2.0), Delta-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Delta-vascular (0.5), arthritis (0.5), TLCO <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for "active to very active" patients. CONCLUSIONS: Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.

Adolescent↗
PubMed2001

The Virtual Brain Project--development of a neurosurgical simulator.

As a joined project between Aalborg University and Aalborg Hospital Denmark, a neuro-surgical simulator is being developed. In this paper the objective of the project is outlined and an overview of the research activities within the project is given. Focus is on 3D modelling of the brain, deformable models and the development of two demonstrators, including one for training of punctuation of ventricle using visual and haptic feedback.

Anatomy, Cross-Sectional↗
PubMed2001

Magnetic resonance imaging of the wrist and finger joints in patients with inflammatory joint diseases.

OBJECTIVE: To study magnetic resonance imaging (MRI) features in the wrist and metacarpophalangeal (MCP), proximal interphalangeal (PIP), and distal interphalangeal (DIP) joints in 4 patient groups: early rheumatoid arthritis (RA) (< 3 yrs); established RA (> 3 yrs); other arthritis; arthralgia. METHODS: MRI was obtained before and after contrast (gadodiamide) injection of the wrist and finger joints in 103 patients and 7 controls. The study included: (1) 28 patients with disease duration < 3 yrs who fulfilled the American College of Rheumatology (ACR) criteria for RA; (2) 25 patients with RA disease duration > 3 yrs who fulfilled the ACR criteria. (3) 25 patients with reactive arthritis, psoriatic arthritis, or mixed connective tissue disease; and (4) 25 patients with arthralgia. The following MRI variables were assessed: number of joints with enhancement after contrast injection, number of joints with joint fluid, and number of bones with edema in the wrist and fingers. The volume of the enhancing synovial membrane after contrast injection in the MCP, PIP, and DIP joints was manually outlined. MR images were scored independently under blinded conditions. RESULTS: Bone marrow edema was found in 68% of the patients with established RA, and the number of bones with edema was significantly higher in patients with established RA compared to patients with early RA, other arthritis, and arthralgia (Mann-Whitney p < 0.04). Bone edema was not found in patients with arthralgia. There was marked overlap within and between the patient groups. No differences in MRI features were found between patients with early RA and patients with other arthritis. The volumes of the synovial membrane in the MCP, PIP, and DIP joints were significantly higher in patients with arthritis compared to patients with arthralgia. CONCLUSION: Although there was marked overlap between the arthritis patient groups, MRI determined bone marrow edema and synovial membrane volumes provided additional information about disease activity and may be used as a marker of it. Bone marrow edema appeared with the highest percentage in patients with long duration of RA (> 3 yrs) and is probably secondary to changes in inflammatory activity.

Acute-Phase Proteins↗