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Biomedical subjects

S Hansen

Publications and source records attributed to S Hansen.

At least 37 records · Page 2Linked to original sources
PubMed2003

Independent prognostic value of angiogenesis and the level of plasminogen activator inhibitor type 1 in breast cancer patients.

Tumour angiogenesis and the levels of plasminogen activator inhibitor type 1 (PAI-1) are both informative prognostic markers in breast cancer. In cell cultures and in animal model systems, PAI-1 has a proangiogenic effect. To evaluate the interrelationship of angiogenesis and the PAI-1 level in breast cancer, we have evaluated the prognostic value of those factors in a total of 228 patients with primary, unilateral, invasive breast cancer, evaluated at a median follow-up time of 12 years. Microvessels were immunohistochemically stained by antibodies against CD34 and quantitated by the Chalkley counting technique. The levels of PAI-1 and its target proteinase uPA in tumour extracts were analysed by ELISA. The Chalkley count was not correlated with the levels of uPA or PAI-1. High values of uPA, PAI-1, and Chalkley count were all significantly correlated with a shorter recurrence-free survival and overall survival. In the multivariate analysis, the uPA level did not show independent prognostic impact for any of the analysed end points. In contrast, the risk of recurrence was independently and significantly predicted by both the PAI-1 level and the Chalkley count, with a hazard ratio (95% CI) of 1.6 (1.01-2.69) and 1.4 (1.02-1.81), respectively. For overall survival, the Chalkley count, but not PAI-1, was of significant independent prognostic value. The risk of death was 1.7 (1.30-2.15) for Chalkley counts in the upper tertile compared to the lower one. We conclude that the PAI-1 level and the Chalkley count are independent prognostic markers for recurrence-free survival in patients with primary breast cancer, suggesting that the prognostic impact of PAI-1 is not only based on its involvement in angiogenesis.

Adult↗
PubMed2003

Exploring the link between character, personality disorder, and neuropsychological function.

Personality deviations and deficits in cognitive executive function are common among forensic populations. The present study on incarcerated offenders explored whether there are links between the two domains. Personality was assessed using the Temperament and Character Inventory (TCI). Neuropsychological performance, including visual working memory, attentional set-shifting and planning, were tested with the Cambridge Neuropsychological Test Automated Battery (CANTAB). Subjects with personality disorders scored high on harm avoidance, and low on self-directedness and cooperativeness. Personality disordered offenders did not differ from the comparison groups (offenders without personality disorder, and non-criminal controls) with regard to CANTAB measures of visual working memory (delayed matching to sample, spatial working memory) and planning (Stockings of Cambridge), but they made a larger number of errors on the attentional set-shifting task. Dimensional analysis of the personality and neuropsychological variables revealed significant associations between self-directedness and cooperativeness on the one hand, and attentional set-shifting on the other. Intellectually disabled, non-criminal individuals (marginal mental retardation) who performed poorly on attentional set-shifting also scored low on self-directedness and cooperativeness. The results indicate that poor development of certain personality traits may be associated with deficits in neuropsychological functioning.

Adult↗
PubMed2003

Combined epirubicin and vinorelbine as first-line therapy in metastatic breast cancer: a pilot study performed by the Danish Breast Cancer Cooperative Group.

This pilot study investigated the tolerability and efficacy of increasing doses of epirubicin and vinorelbine as first-line chemotherapy for metastatic breast cancer. Acute toxicity was manageable at all dose levels for combinations of epirubicin 60-90 mg/m2 on day 1 and vinorelbine 15-25 mg/m2 on days 1 and 8 repeated every 3 weeks. Myelotoxicity was the most frequent toxic event, with a significant increase in grade 4 leukopenia from 0% at dose level 1 (60+15 mg/m2) to 26% at dose level 6 (90+25 mg/m2). Signs of acute or chronic cardiotoxicity grades 2-4 were seen in 15% of the patients and included arrhythmia and decreased function. No significant association was established between dose and nonhematological toxicity. Objective responses were observed in 49 of the 99 evaluable patients (49.5%, 95% CI 39.9-59.2), 18 being complete and 31 partial responses. Responses were observed at all six dose levels. In conclusion, acute toxicity was manageable at all dose levels for combinations of epirubicin 60-90 mg/m2 on day 1 and vinorelbine 15-25 mg/m2 on days 1 and 8. In the treatment of advanced breast cancer, improvement of the antitumor efficacy by the addition of vinorelbine to epirubicin remains to be demonstrated in a randomized phase III trial.

Adult↗
PubMed2003

Prader-Willi syndrome: clinical picture, psychosocial support and current management.

AIM: Prader-Willi syndrome (PWS) is a rare, genetically based disorder that occurs in about 1 of 15 000 live-born children. To raise a child with PWS is challenging for parents and requires support from multiprofessional habilitation services. This paper maps the need for psychosocial support and current management of children and adolescents with PWS. METHOD: Parents to 58 children with PWS (aged 5-18 years) completed questionnaires covering clinical, diagnostic and psychosocial issues. RESULTS: The children received their diagnosis at a mean age of 2.5 year. Growth hormone treatment was given to 72%. Sixty-three per cent of the sample was not overweight. Neuropsychiatric symptoms were common from early age and some were related to obesity. Most parents wanted information as to availability of external resources and future child needs. Few parents needed family-directed support. CONCLUSION: The overall impression is that the eating disorder is managed relatively well. Even so PWS symptoms typically exacerbate over time and consequently parents need continuous support throughout childhood and adolescence. Greater attention should be paid to idiosyncrasies in cognitive functioning and to clinical markers of neuropsychiatric problems.

Adolescent↗
PubMed2003

Rituals and compulsivity in Prader-Willi syndrome: profile and stability.

BACKGROUND: Prader-Willi syndrome (PWS) is characterized by an increased risk for obsessive-compulsive disorder. This study investigated the nature of compulsive-like behaviours in the PWS. METHOD: Parents of 50 individuals with PWS (aged 5-18 years) and 50 typically developing 4-year-old children completed the Childhood Routines Inventory. This instrument measures compulsive-like behaviours in normative childhood. RESULTS: Many childhood compulsive behaviours are prevalent among older children and adolescents with PWS. Group differences were observed in that the PWS group, independent of age, gender and cognitive dysfunctions, exhibited more intense compulsive behaviours related to insistence on sameness in many daily activities and social contexts. Findings also revealed an age-independent low-prevalent pattern of PWS compulsivity, probably related to other features in the PWS symptomatology. CONCLUSIONS: Compulsions of childhood do not subside with age in adolescents with PWS. The findings indicate that the differentiation between delayed childhood rituals and pathological manifestations of compulsive features is complex in PWS populations.

Adolescent↗
PubMed2002

Coupling of antagonistic ankle muscles during co-contraction in humans.

In 35 healthy human subjects coupling of EMGs recorded from the tibialis anterior (TA) and soleus (Sol) muscles during voluntary co-contraction was analysed in the time and frequency domains. Two patterns were observed in different subjects or in the same subject on different occasions. One pattern consisted of central peaks in the cumulant density function of the two signals, which was often accompanied by coherence in the 15-35 Hz frequency band. The other pattern consisted of a central trough in the cumulant density function, which was mostly accompanied by coherence around 10 Hz. When this was the case oscillations were usually observed in the cumulant density function with time lags of 100 ms. Both patterns could be observed in the same subject, but usually not at the same time. Coherence around 10 Hz associated with a central trough in the cumulant density function was less common during weak than during strong co-contraction. The central peak with coherence in the 15-35 Hz frequency band in contrast tended to be most common during weak contraction. There was a tendency for the 10-Hz coherence with central trough to occur when the contractions had been maintained for some time. Both patterns could be observed when sensory feedback in large diameter afferents was blocked by ischaemia. When a central peak with coherence in the 15-35 Hz frequency band was observed for paired TA and Sol EMG recordings (10 out of 19 subjects), a coupling in the same frequency band was also observed between the EMG activities from the two muscles and the EEG activity recorded from the leg area of the motor cortex. When the central trough and the coherence around 10 Hz was observed for the EMG recordings (8 out of 19 subjects), no significant coherence was observed between EEG and EMG in 7 of the 8 subjects. In the last subject coherence around 10 Hz was observed. It is suggested that these findings signify the existence of two different central input systems to antagonistic ankle motoneurones: one input activates one muscle while depressing the antagonist and the other coactivates antagonistic motoneurones. The data suggest that at least the latter input depends on motor cortical activity.

Action Potentials↗
PubMed2002

Express subcutaneous IgG infusions: decreased time of delivery with maintained safety.

The aims of the study were to evaluate the safety and feasibility of weekly express subcutaneous replacement IgG self-infusions (E-SCIG, 35 mL/h/syringe driver) in 50 patients and to evaluate their perceptions of the therapy. A total of 4900 E-SCIG infusions at separate infusion sites were given on 1228 treatment occasions. The most commonly reported local tissue reactions were swelling (n = 37), redness (n = 25), and soreness (n = 24). A majority of these patients reported the local reactions as less intense or unchanged compared to those arising from rapid SCIG (20 mL/h) infusions. The patients reported a median score of 16 (visual analogue scale, VAS; 1, not troublesome at all) regarding their overall perceptions of the local reactions. They were positive toward the home therapy regime (median VAS score 96; 100, very positive) and anxious to continue with the E-SCIG infusions (median VAS score 98; 100, very anxious). The E-SCIG method seems to be safe, with few pronounced local reactions, and is appreciated by the patients. Express delivery could also potentially facilitate IgG delivery in a wide variety of diseases, such as autoimmune and autoimmune-like conditions of a neurological or rheumatological character.

Administration, Cutaneous↗
PubMed2002

[Surveillance of postoperative wound infections: reference data of the Hospital Infection Surveillance System (KISS)].

BACKGROUND: Surgical site infections (SSI), the third-most-frequent nosocomial infection, are a problem in all fields of surgery. Assessing the level of one's own infection rates is often difficult, since there have been no suitable comparative data available in Germany in the past due to the lack of a uniform method of determining these rates. METHODS: Based on an American model, the Hospital Infection Surveillance System (KISS) has been carrying out a standard recording of SSI since 1997 in meanwhile 132 surgical departments of 89 hospitals. Specially trained hygiene personnel record SSI according to CDC definitions in selected indicator operations. RESULTS: Since January 1997, 1,549 SSI have been recorded in 71,038 operations using 13 different surgical techniques. The risk-ratified SSI rates for each of these surgical techniques are provided and can serve as orientational data for other departments. CONCLUSION: The KISS reference data can help in assessing one's own SSI rates. A prerequisite is surveillance according to the KISS protocol.

Confidence Intervals↗
PubMed2002

The scavenger receptor, cysteine-rich domain-containing molecule gp-340 is differentially regulated in epithelial cell lines by phorbol ester.

Gp-340 is a glycoprotein belonging to the scavenger receptor cysteine rich (SRCR) group B family. It binds to host immune components such as lung surfactant protein D (SP-D). Recent studies found that gp-340 interacts directly with pathogenic microorganisms and induces their aggregation, suggesting its involvement in innate immunity. In order to investigate further its potential immune functions in the appropriate cell lines, the expression of gp-340 in four conventional immune cell lines (U937, HL60, Jurkat, Raji), and two innate immune-related epithelial cell lines (A549 derived from lung and AGS from stomach), was examined by RT-PCR and immunohistochemistry. The resting immune cell lines showed weak or no gp-340 mRNA expression; while the two epithelial cell lines expressed gp-340 at much higher level, which was differentially regulated by phorbol myristate acetate (PMA) treatment. In the A549 cells, gp-340 was up-regulated along with the PMA-induced proinflammatory expression of both IL-6 and IL-8. In AGS cells, PMA down-regulation of gp-340 was seen in parallel with an up-regulation of the two mature gastric epithelial specific proteins TFF1 (trefoil factor 1) and TFF2, which are implicated as markers of terminal differentiation. Analysis of the distribution of gp-340, together with the TFFs and SP-D in normal lung and gastric mucosa, supported further our in vitro data. We conclude that the differential regulation of gp-340 in the two epithelial cell lines by PMA indicates that gp-340 s involvement in mucosal defence and growth of epithelial cells may vary at different body locations and during different stages of epithelial differentiation.

B-Lymphocytes↗
PubMed2002

[Influence of probiotics and fibre on the incidence of bacterial infections following major abdominal surgery - results of a prospective trial].

INTRODUCTION: Early enteral nutrition with fibre and probiotics has been effective in preventing bacterial translocation and is therefore expected to reduce the incidence of postoperative bacterial infections. PATIENTS AND METHODS: In a prospective randomized trial including 172 patients following major abdominal surgery or liver transplantation, the incidence of bacterial infections was compared in patients receiving either a) conventional parenteral or enteral nutrition, b) enteral nutrition with fibre and lactobacillus plantarum 299 or c) enteral nutrition with fibre and heat inactivated lactobacilli (placebo). Liver transplant recipients were also treated with selective bowel decontamination (SBD). Routine laboratory parameters, nutritional parameters and the cellular immune status were measured preoperatively and on postoperative days 1, 5 and 10. RESULTS: Patients were comparable regarding preoperative ASA-classification, Child-Pugh classification of cirrhosis, operative data and immunosuppression. The incidence of bacterial infections after liver, gastric oder pancreas resection was 31 % in the conventional group a) compared to 4 % in the lactobacillus-group b) and 13 % in the placebo-group c). In the analysis of 95 liver transplant recipients, 13 % group b)-patients developed infections compared to 48 % group a)-patients and 34 % group c)-patients. The difference between groups a) and b) was statistically significant in both cases. In addition, the duration of antibiotic therapy was significantly shorter in the lactobacillus-group. Cholangitis and pneumonia were the most frequent infections and enterococci the most frequently isolated bacteria. Fibre and lactobacilli were well tolerated in most cases. CONCLUSION: Fibre and probiotics could lower the incidence of bacterial infections following major abdominal surgery in comparison to conventional nutrition with or without SBD. With this new concept, costs can be reduced by shortening the duration of antibiotic therapy and sparing SBD.

Adult↗
PubMed2002

A clinical neurological, neurophysiological, and neuropsychological study of sheep farmers and dippers exposed to organophosphate pesticides.

OBJECTIVES: To classify clinical diseases of the subjects with abnormal indices of peripheral neuropathy identified in field studies of sheep farmers and dippers exposed to organophosphate pesticides. To explore what neuropsychological profiles, if any, may be associated with neurophysiological damage in these subjects. METHODS: A case-control study (79 subjects) nested within the cross sectional study (685 subjects) of sheep farmers from the field study. Three groups with no, possible, and probable or definite neuropathy according to field studies were recruited. Investigations comprised symptoms of neuropathy, neurologial signs, motor and sensory nerve conduction, electromyography, quantitative sensory testing, and neuropsychological tests. RESULTS: The incidence of clinical neuropathy increased from 7% in the no neuropathy group to 52% in the probable or definite neuropathy group based on nerve conduction measurements or presence of neurological signs. Sensory abnormalities were found more often than motor deficits. Small diameter nerve fibres were also affected more than large fibres. CONCLUSIONS: The neuropathy is predominantly sensory and is characteristic of distal, chronic neuropathy with no acute features. Small fibre populations are affected more than large fibre populations. Increasing severity of neuropathy was associated with anxiety and depression as measured in the neuropsychological tests.

Adolescent↗
PubMed2002

Clinical validation of methods of diagnosis of neuropathy in a field study of United Kingdom sheep dippers.

OBJECTIVES: To investigate the reproducibility of measured indices of chronic peripheral neuropathy from a field study of sheep dippers when compared with similar measurements carried out in a clinical setting. METHODS: A stratified random sample of field study subjects was invited to attend a clinic. Neuropathy was measured both in the field and at the clinic with a modified version of a standard symptoms questionnaire and quantitative sensory thresholds for hot, cold, and vibration. These were combined into a classification of the likelihood of neuropathy with a neuropathy scoring system. Indicators of sensory abnormality were based on comparison of sensory thresholds to age dependent reference values derived from an external reference group. RESULTS: Only 51% of subjects were assigned similar classifications in the field and clinic based on the neuropathy scoring system. Of the component indices, grouped symptom scores, with 65% of subjects showing exact agreement, proved to be more reproducible than quantitative sensory test indicators. There were biases in the comparison of field and clinic measurements of hot and vibration sensations, but no evidence of greater variation between individual people in sensory thresholds in the field relative to at the clinic. CONCLUSIONS: The neuropathy scoring system proved to be of limited reproducibility, due in a large part to the lack of reproducibility of the indicators of sensory test abnormality caused by inadequate temperature control. However, the symptoms score and measured sensory thresholds could be used separately as indices of neuropathy in exposure-response analyses.

Adult↗
PubMed2002

Comparison of two bioassay techniques for assessing the acute toxicity of pesticides to chironomid larvae (Diptera: Chironomidae).

Two container and substrate combinations were compared to determine which provided optimal survival of larvae of Chironomus tepperi and Glyptotendipes paripes in the absence of toxicants. Unfed final-stage larvae of G. paripes survived significantly (P < 0.05) better in waxed paper cups with sand substrate (92.8% after 3 days) than in glass tubes with a shredded paper substrate (85.3%). Survival of larvae of C. tepperi over the same period did not differ significantly in the 2 systems. Larvae of C. tepperi were bioassayed against 3 insecticides (technical and formulated imidacloprid, chlorpyrifos, and betacypermethrin) with both container and substrate combinations. Median lethal concentration values (24 h) obtained with waxed cups with sand were 1.8 times higher on average than those obtained with glass tubes with shredded paper (range 1.13-2.65 times). To determine the cause of this variability, solid-phase microextraction was used to measure changes in chlorpyrifos availability over time in the 2 bioassay systems. Chlorpyrifos concentrations in the waxed cups and sand system fell from 7.50 to 3.36 microg/liter over 24 h, probably as a consequence of chemical adsorption to the waxed surfaces. Chlorpyrifos concentrations in the glass tubes and paper system remained unchanged over this period. Excluding substrates from the containers had only a minor effect on chlorpyrifos availability. These results demonstrate that the behaviors of both test organisms and toxicants within bioassay systems need to be understood if the data generated with different systems are to be compared. Understanding how toxicant availability is affected by different container and substrate types is particularly important where bioassays are conducted with nominal concentration values rather than analytically determined exposure concentrations.

Animals↗
PubMed2001

NMR spectroscopy reveals the solution dimerization interface of p53 core domains bound to their consensus DNA.

The p53 protein is a transcription factor that acts as the major tumor suppressor in mammals. The core DNA-binding domain is mutated in about 50% of all human tumors. The crystal structure of the core domain in complex with DNA illustrated how a single core domain specifically interacts with its DNA consensus site and how it is inactivated by mutation. However, no structural information for the tetrameric full-length p53-DNA complex is available. Here, we present novel experimental insight into the dimerization of two p53 core domains upon cooperative binding to consensus DNA in solution obtained by NMR. The NMR data show that the p53 core domain itself does not appear to undergo major conformational changes upon addition of DNA and elucidate the dimerization interface between two DNA-bound core domains, which includes the short H1 helix. A NMR-based model for the dimeric p53 core-DNA complex incorporates these data and allows the conclusion that the dimerization interface also forms the actual interface in the tetrameric p53-DNA complex. The significance of this interface is further corroborated by the finding that hot spot mutations map to the H1 helix, and by the binding of the putative p53 inhibitor 53BP2 to this region via one of its ankyrin repeats. Based on symmetry considerations it is proposed that tetrameric p53 might link non-contiguous DNA consensus sites in a sandwich-like manner generating DNA loops as observed for transcriptionally active p53 complexes.

Amino Acid Sequence↗
PubMed2001

Transcriptional transactivation by selected short random peptides attached to lexA-GFP fusion proteins.

BACKGROUND: Transcriptional transactivation is a process with remarkable tolerance for sequence diversity and structural geometry. In studies of the features that constitute transactivating functions, acidity has remained one of the most common characteristics observed among native activation domains and activator peptides. RESULTS: We performed a deliberate search of random peptide libraries for peptides capable of conferring transcriptional transactivation on the lexA DNA binding domain. Two libraries, one composed of C-terminal fusions, the other of peptide insertions within the green fluorescent protein structure, were used. We show that (i) peptide sequences other than C-terminal fusions can confer transactivation; (ii) though acidic activator peptides are more common, charge neutral and basic peptides can function as activators; and (iii) peptides as short as 11 amino acids behave in a modular fashion. CONCLUSIONS: These results support the recruitment model of transcriptional activation and, combined with other studies, suggest the possibility of using activator peptides in a variety of applications, including drug development work.

Journal Article↗
PubMed2001

Incidence of Hodgkin's disease in Nordic countries.

We analysed age and sex-specific trends in the incidence of Hodgkin's lymphoma in Denmark, Sweden, Norway, and Finland during 1978-97. The incidence of Hodgkin's lymphoma decreased significantly in all age groups above 40 years; there was a significant increase in incidence among adolescents and young adults. This increase occurred primarily for Hodgkin's lymphoma of the nodular sclerosis subtype. These observations emphasise the need to identify risk factors for Hodgkin's lymphoma in the young.

Adolescent↗