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Biomedical subjects

B Hagen

Publications and source records attributed to B Hagen.

At least 19 recordsLinked to original sources
PubMed2003

Seroprevalence of Lawsonia intracellularis in large pig production units.

In 11 'farrow-to-finish' outdoor or indoor production units, blood samples from late pregnant gilts were tested by indirect immunofluorescence antibody (IFA) serum assay for Lawsonia intracellularis. The offspring of positively tested gilts were tested at 2, 7, 12, 17, 22 and 27 weeks of age for seroprevalence of Lawsonia intracellularis. All offspring of IFA positive gilts were seronegative at 2 and 7 weeks of age. At 12 weeks of age 81.0% of indoor and 51.0% of outdoor pigs were tested positive. While at 17 weeks of age 82.5% of indoor-raised pigs showed seropositivity, in outdoor units the seropositivity declined to 31.3%. At weeks 22 and 27 indoor-raised pigs still showed marked seropositivity (17.7% and 11.5%) but their outdoor-raised counterparts revealed declining values (7.4% and 0%).

Animal Husbandry↗
PubMed2001

[Can human papillomavirus testing and vaccination prevent cervical cancer?].

BACKGROUND: Cervical cancer is the third most frequent cancer among women worldwide. Human papillomavirus (HPV) infection is a necessary risk factor and the first step in cervical carcinogenesis. MATERIAL AND METHODS: This article reviews the current literature concerning the possibility of preventing cervical cancer by HPV testing and vaccination. RESULTS: HPV testing cannot replace cytology, but will reduce false negative cytology and may improve the screening programme for cervical neoplasia. It has not yet been incorporated in any national cervical cancer screening program, but trials are ongoing in Scandinavia and in the Netherlands. The cost-effectiveness of HPV testing in screening has to be proven and whether it can affect the recommended screening-intervals. Therapeutic and prophylactic vaccines for HPV associated disease are in progress. Evaluating the clinical trials that are ongoing will take several years. Several anti-HPV vaccines are now in clinical trials; Norway will also participate. Therapeutic vaccines against cervical cancer have so far not been successful, but anogenital dysplasias and condylomas may be more susceptible. Prophylactic vaccines against HPV 6, 11, 16 and 18 have been evaluated in clinical phase I and II trials, and phase III trials are in progress. INTERPRETATION: HPV testing improves the specificity and sensitivity of cervical cytology and it can be used to clarify cases with atypical cells of undetermined significance (ASCUS) and low-grade intraepithelial neoplasia. In the near future it may also be included in the cervical cancer screening programme for women above the age of 30. The first results in clinical vaccine trials are encouraging, and final conclusions about the effectiveness of these vaccines may be achieved in five years' time.

Female↗
PubMed2001

[Palliative treatment in gynecologic cancer].

BACKGROUND: Data on the need for palliative care related to disease groups are very limited. MATERIAL AND METHODS: A retrospective analysis was performed on the hospital records of 228 patients who died from gynaecologic cancer during the 1988-1997 period. RESULTS: 76% of deaths took place in hospital; 12% at home. Median terminal hospital stay was 13 days. Symptoms from intestinal obstruction were dominating in 30% of cases and most frequently seen in patients with ovarian cancer. Palliative intestinal surgery was performed in 38% of patients with ovarian cancer, median survival being 5 months (range 10 days-7 years), perioperative mortality (within 30 days) 13%. Cachexia dominated in 27% and was more often present when death occurred at home. Assistance from a gastroenterologic surgeon, urologist, haematologist or anaesthesiologist was needed in 32% of cases. One in two patients received parenteral pain relief in the terminal phase, for a median period of five days. Palliative radiotherapy was given 21% of the patients, most often in cervical and endometrial cancer, and chemotherapy or hormonal therapy was used in 36%. Minor interventions like laparocentesis, pleurocentesis, tumour resections, and various forms of urinary deviations were frequent. INTERPRETATION: Hospital deaths are more common among patients suffering from gynaecologic cancer than among cancer patients in general (55% in Norway), and the need for multimodal hospital service is large. We see substantial benefits in the Norwegian model in which a gynaecologist experienced in oncology has comprehensive responsibility for the treatment, supported by other specialists and the primary health service.

Adult↗
PubMed2001

Mapping and fitting the peripheral benzodiazepine receptor binding site by carboxamide derivatives. Comparison of different approaches to quantitative ligand-receptor interaction modeling.

The synthetic-computational approach to the study of the binding site of peripheral benzodiazepine receptor (PBR) ligands related to 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195, 1) within their receptor (Cappelli et al. J. Med. Chem. 1997, 40, 2910-2921) has been extended. A series of carboxamide derivatives endowed with differently substituted planar aromatic or heteroaromatic systems was designed with the aim of getting further information on the topological requisites of the carbonyl and aromatic moieties for interaction with the PBR binding site. The synthesis of most of these compounds involves Weinreb amidation of the appropriate lactone as the key step. The most potent compound, among the newly synthesized ones, shows a nanomolar PBR affinity similar to that shown by 1 and the presence of a basic N-ethyl-N-benzylaminomethyl group in 3-position of the quinoline nucleus. Thus, it may be considered the first example of a new class of water soluble derivatives of 1. Several computational methods were used to furnish descriptors of the isolated ligands (indirect approaches) able to rationalize the variation in the binding affinity of the enlarged series of compounds. Sound QSAR models are obtained by size and shape descriptors (volume approach) which codify for the short-range contributions to ligand-receptor interactions. Molecular descriptors which explicitly account for the electrostatic contribution to the interaction (CoMFA, CoMSIA, and surface approaches) perform well, but they do not improve the quantitative models. Moreover, useful hints for the identification of the antagonist binding site in the three-dimensional modeling of the receptor (direct approach) were provided by the receptor hypothesis derived by the pharmacophoric approach. The ligand-receptor complexes obtained provided a detailed description of the modalities of the interaction and interesting suggestions for further experiments.

Amino Acid Sequence↗
PubMed2001

10-Gy single-fraction pelvic irradiation for palliation and life prolongation in patients with cancer of the cervix and corpus uteri.

OBJECTIVE: The goal of this study was to evaluate the effects of single fractions of 10 Gy pelvic irradiation for palliation and life prolongation in patients with cancer of the uterine cervix or corpus. METHODS: A retrospective analysis was performed on 37 cervical cancer and 27 corpus cancer patients treated in the period 1988-1998. All patients had a life expectancy of less than 1 year. Due to stage of disease, age (median 82 years), or comorbidity they were considered unapt for surgery or conventional radiotherapy. Eleven patients with recurrence within irradiated field or early progression received one, 51 patients received two, and 2 patients received three fractions with a 4-week interval. RESULTS: Vaginal bleeding stopped in 90% and malodorous discharge in 39% of the patients. Among 46 patients with advanced disease treated for palliation, 10 (22%) showed complete tumor responses. Median time to progression was 6 months, and median survival, 9 months. Eighteen patients with early-stage disease and serious comorbidity were treated with life prolongation and symptom prevention as intention, and showed seven complete responses. Median survival was 13 months, and half the deaths were caused by intercurrent disease. Median hospital stay was 5 days and rehabilitation was easy. Fifty-six percent of the patients experienced no acute side effects and 33% had minor gastrointestinal problems. Three patients (6%) had serious late bowel complications, one with a fatal outcome, the symptoms appearing 9-10 months posttreatment. CONCLUSION: The 10-Gy single-fraction pelvic radiation regimen is an effective means of symptom palliation and is well tolerated. Tumor responses are obtained. The risk of late bowel complications is a concern for patients with a life expectancy greater than 9 months.

Adenocarcinoma↗
PubMed2001

[Non-medicamentous therapy and prevention of Alzheimer disease].

An overview of prevalence data and empirically documented risk factors of a dementia is followed by a short description of intervention strategies. After this, prevalence data from the SIMA Study are presented and results of the multivariate analyses of early indicators and risk factors are discussed. The last section is dedicated to the risk decreasing effects of a combined memory and psychomotor training program which was developed within the study's scope.

Aged↗
PubMed2001

Genetic epidemiology of BRCA1 mutations in Norway.

Familial breast-ovarian cancer has been demonstrated to be frequent but unevenly distributed in Norway. This was assumed to be caused by the reduced population size created by the medieval Bubonic plagues 25 generations ago, and by the following rapid expansion. We have previously reported that four mutations account for 68% of the BRCA1 mutation carriers. Subsequent analysis has resulted in a total of 100 separate families carrying one of these founder mutations. The four mutations occurred on one specific BRCA1 haplotype each. The 1675delA, 816delGT and 3347delAG families originated from the South-West coast of Norway with a few families in the north, while the traceable ancestors of the 1135insA families clustered along the historical inland road from the South-East to mid-Norway. The carriers of each of the four mutations today are descendants of one or a few individuals surviving the plagues. We may identify the majority of BRCA1 mutation carriers in Norway by screening for local founder mutations.

Breast Neoplasms↗
PubMed2001

Comparison of 'pattern recognition' and logistic regression models for discrimination between benign and malignant pelvic masses: a prospective cross validation.

OBJECTIVES: To test prospectively the diagnostic performance of two logistic regression models for calculation of individual risk of malignancy in adnexal tumors (the 'Tailor model' and the 'Timmerman model'), and to compare them to that of 'pattern recognition' (subjective evaluation of the gray-scale ultrasound image and color Doppler ultrasound examination). DESIGN: Consecutive women with a pelvic mass judged clinically to be of adnexal origin underwent preoperative ultrasound examination including color and spectral Doppler examination. The same examination techniques and definitions as those used in the studies in which the logistic regression models had been created were used. The Tailor model was tested in 133 women (35 of whom hada malignancy) and the Timmerman model in 82 women (29 of whom had a malignancy). A subset of 79 women (28 of whom had a malignancy) was used to compare the performance of the Tailor model and the Timmerman model by calculating and comparing the areas under the receiver operating characteristics curves of the two models. Sensitivity and specificity with regard to malignancy were calculated for all three methods. RESULTS: Pattern recognition performed better than the two logistic regression models (sensitivity around 85%, specificity around 90%). Using a risk of malignancy of > 50% to indicate malignancy (as suggested in the original publications), the sensitivity of the Tailor model was 69% and the specificity 88% (n = 133). The corresponding values for the Timmerman model were 62% and 79% (n = 82). The receiver operating characteristics curves showed the two logistic regression models to have similar diagnostic properties (area under the curve, 0.87 vs. 0.84; P = 0.25; n = 79). The diagnostic performance of the mathematical models was much poorer in this study than in those in which the models had been created. CONCLUSION: The poor diagnostic performance of the mathematical models can probably be explained by subtle differences in definitions and examination technique and by differences between the original tumor populations and the study population. For mathematical models to be generally useful, they probably need to be created on the basis of a very large number of tumors, and the variables in the model must be unequivocally defined and the examination technique meticulously standardized.

Adenofibroma↗
PubMed2001

Muscarinic stimulation increases basal Ca(2+) and inhibits spontaneous Ca(2+) transients in murine colonic myocytes.

Localized Ca(2+) transients in isolated murine colonic myocytes depend on Ca(2+) release from inositol 1,4,5-trisphosphate (IP(3)) receptors. Localized Ca(2+) transients couple to spontaneous transient outward currents (STOCs) and mediate hyperpolarization responses in these cells. We used confocal microscopy and whole cell patch-clamp recording to investigate how muscarinic stimulation, which causes formation of IP(3), can suppress Ca(2+) transients and STOCs that might override the excitatory nature of cholinergic responses. ACh (10 microM) reduced localized Ca(2+) transients and STOCs, and these effects were associated with a rise in basal cytosolic Ca(2+). These effects of ACh were mimicked by generalized rises in basal Ca(2+) caused by ionomycin (250-500 nM) or elevated external Ca(2+) (6 mM). Atropine (10 microM) abolished the effects of ACh. Pretreatment of cells with nicardipine (1 microM), or Cd(2+) (200 microM) had no effect on responses to ACh. An inhibitor of phospholipase C, U-73122, blocked Ca(2+) transients and STOCs but did not affect the increase in basal Ca(2+) after ACh stimulation. Xestospongin C (Xe-C; 5 microM), a membrane-permeable antagonist of IP(3) receptors, blocked spontaneous Ca(2+) transients but did not prevent the increase of basal Ca(2+) in response to ACh. Gd(3+) (10 microM), a nonselective cation channel inhibitor, prevented the increase in basal Ca(2+) after ACh and increased the frequency and amplitude of Ca(2+) transients and waves. Another inhibitor of receptor-mediated Ca(2+) influx channels, SKF-96365, also prevented the rise in basal Ca(2+) after ACh and increased Ca(2+) transients and development of Ca(2+) waves. FK-506, an inhibitor of FKBP12/IP(3) receptor interactions, had no effect on the rise in basal Ca(2+) but blocked the inhibitory effects of increased basal Ca(2+) and ACh on Ca(2+) transients. These results suggest that the rise in basal Ca(2+) that accompanies muscarinic stimulation of colonic muscles inhibits localized Ca(2+) transients that could couple to activation of Ca(2+)-activated K(+) channels and reduce the excitatory effects of ACh.

Acetylcholine↗
PubMed2001

Coupling strength between localized Ca(2+) transients and K(+) channels is regulated by protein kinase C.

Localized Ca(2+) transients resulting from inositol trisphosphate (IP(3))-dependent Ca(2+) release couple to spontaneous transient outward currents (STOCs) in murine colonic myocytes. Confocal microscopy and whole cell patch-clamp techniques were used to investigate coupling between localized Ca(2+) transients and STOCs. Colonic myocytes were loaded with fluo 3. Reduction in external Ca(2+) ([Ca(2+)](o)) reduced localized Ca(2+) transients but increased STOC amplitude and frequency. Simultaneous recordings of Ca(2+) transients and STOCs showed increased coupling strength between Ca(2+) transients and STOCs when [Ca(2+)](o) was reduced. Gd(3+) (10 microM) did not affect Ca(2+) transients but increased STOC amplitude and frequency. Similarly, an inhibitor of Ca(2+) influx, 1-2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole (SKF-96365), increased STOC amplitude and frequency. A protein kinase C (PKC) inhibitor, GF-109203X, also increased the amplitude and frequency of STOCs but had no effect on Ca(2+) transients. Phorbol 12-myristate 13-acetate (1 microM) reduced STOC amplitude and frequency but did not affect Ca(2+) transients. 4alpha-Phorbol (1 microM) had no effect on STOCs or Ca(2+) transients. Single channel studies indicated that large-conductance Ca(2+)-activated K(+) (BK) channels were inhibited by a Ca(2+)-dependent PKC. In summary 1) Ca(2+) release from IP(3) receptor-operated stores activates Ca(2+)-activated K(+) channels; 2) Ca(2+) influx through nonselective cation channels facilitates activation of PKC; and 3) PKC reduces the Ca(2+) sensitivity of BK channels, reducing the coupling strength between localized Ca(2+) transients and BK channels.

Animals↗
PubMed2001

Nursing home placement. Factors affecting caregivers' decisions to place family members with dementia.

Nurses who work with older adults with dementia in the community are aware of how difficult it can be for family members to make placement-related decisions, and need research-based information to help families make these decisions. This article presents the results of a qualitative research study intended to explore the factors influencing caregivers' decision-making process related to placing an elderly family member with dementia in a nursing home. Using the study findings, the author suggests a theory which helps to explain some of the decision-making factors which appear to influence caregivers' abilities to make placement-related decisions. The nursing implications of this theory, and recommendations for future research, are presented.

Aged↗
PubMed2000

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass.

Our objective was to compare the predictive value of the well-established tumour marker CA125 with the newer tumour markers tetranectin (TN), OVX1 and CASA in distinguishing benign and malignant pelvic masses in women. Participants included 185 women, 19 years or older, with a pelvic mass planned for surgical exploration. Significantly different CA125 levels were found between benign tumours and localised ovarian cancer (OC), advanced OC and other non-OCs. Significantly different TN levels were found between benign tumours and advanced OC (stage III/IV), between benign tumours and other cancers and between all OCs and other cancers. For CASA, significant differences were found between benign tumours and all OCs as well as advanced OC. No significant differences could be demonstrated for OVX1. Significant correlations for the 44 OC patients were found between CA125, TN and CASA. No significant correlations were found for OVX1, possibly because of the method used for collection and handling of serum samples. None of the new markers had any additional predictive value compared to CA125. TN and CASA levels correlated with FIGO stage and could be used to discriminate between benign and advanced OC. However, in comparison to the performance of CA125, the additional discriminative value of TN and CASA was minor.

Adult↗
PubMed2000

Randomized study on adjuvant chemotherapy in stage I high-risk ovarian cancer with evaluation of DNA-ploidy as prognostic instrument.

PURPOSE: Adjuvant chemotherapy versus observation and chemotherapy at progression was evaluated in 162 patients in a prospective randomized multicenter study. We also evaluated DNA-measurements as an additional prognostic factor. PATIENTS AND METHODS: Patients received adjuvant carboplatin AUC 7 every 28 days for six courses (n = 81) or no adjuvant treatment (n = 81). Eligibility included surgically staged and treated patients with FIGO stage I disease, grade 1 aneuploid or grade 2 or 3 non-clear cell carcinomas or clear cell carcinomas. Disease-free (DFS) and disease-specific (DSS) survival were end-points. RESULTS: Median follow-up time was 46 months and progression was observed in 20 patients in the treatment group and 19 in the control group. Estimated five-year DFS and DSS were 70% and 86% in the treatment group and 71% and 85% in the control group. The hazard ratio was 0.98 (95% confidence interval (95% CI): 0.52-1.83) regarding DFS and 0.94 (95% CI: 0.37-2.36) regarding DSS. No significant differences in DFS or DSS could be seen when the log-rank test was stratified for prognostic variables. Therefore, data from both groups were pooled for the analysis of prognostic factors. DNA-ploidy (P = 0.003), extracapsular growth (P = 0.005), tumor rupture (P = 0.04), and WHO histologic grade (P = 0.04) were significant independent prognostic factors for DFS with P < 0.0001 for the model in the multivariate Cox analysis. FIGO substage (P = 0.01), DNA ploidy (P < 0.05), and histologic grade (P = 0.05) were prognostic for DSS with a P-value for the model < 0.0001. CONCLUSIONS: Due to the small number of patients the study was inconclusive as regards the question of adjuvant chemotherapy. The survival curves were superimposable, but with wide confidence intervals. DNA-ploidy adds objective independent prognostic information regarding both DFS and DSS in early ovarian cancer.

Adenocarcinoma↗
PubMed2000

Intracellular calcium events activated by ATP in murine colonic myocytes.

ATP is a candidate enteric inhibitory neurotransmitter in visceral smooth muscles. ATP hyperpolarizes visceral muscles via activation of small-conductance, Ca(2+)-activated K(+) (SK) channels. Coupling between ATP stimulation and SK channels may be mediated by localized Ca(2+) release. Isolated myocytes of the murine colon produced spontaneous, localized Ca(2+) release events. These events corresponded to spontaneous transient outward currents (STOCs) consisting of charybdotoxin (ChTX)-sensitive and -insensitive events. ChTX-insensitive STOCs were inhibited by apamin. Localized Ca(2+) transients were not blocked by ryanodine, but these events were reduced in magnitude and frequency by xestospongin C (Xe-C), a blocker of inositol 1,4,5-trisphosphate receptors. Thus we have termed the localized Ca(2+) events in colonic myocytes "Ca(2+) puffs. " The P(2Y) receptor agonist 2-methylthio-ATP (2-MeS-ATP) increased the intensity and frequency of Ca(2+) puffs. 2-MeS-ATP also increased STOCs in association with the increase in Ca(2+) puffs. Pyridoxal-phospate-6-azophenyl-2',4'-disculfonic acid tetrasodium, a P(2) receptor inhibitor, blocked responses to 2-MeS-ATP. Spontaneous Ca(2+) transients and the effects of 2-MeS-ATP on Ca(2+) puffs and STOCs were blocked by U-73122, an inhibitor of phospholipase C. Xe-C and ryanodine also blocked responses to 2-MeS-ATP, suggesting that, in addition to release from IP(3) receptor-operated stores, ryanodine receptors may be recruited during agonist stimulation to amplify release of Ca(2+). These data suggest that localized Ca(2+) release modulates Ca(2+)-dependent ionic conductances in the plasma membrane. Localized Ca(2+) release may contribute to the electrical responses resulting from purinergic stimulation.

Adenosine Triphosphate↗
PubMed2000

Primary treatment of cervical carcinoma. Ten years experience from one Norwegian health region.

OBJECTIVE: To study the primary care of cervical carcinoma with regard to clinical and pathological factors, treatment decisions, complications and survival. DESIGN: A historical cohort comprising all women hospitalized with invasive cervical carcinoma (n=293) during the period 1987-1996. RESULTS: Median age was 52 years (range 23-90). FIGO stage distribution was 62%, 15%, 18% and 5% in stages I, II, III and IV, respectively. Early stage disease correlated with young age. Histologic types were: squamous cell carcinoma 84%, adenocarcinoma 11%, adenosquamous carcinoma 4% and small cell/anaplastic carcinoma 1%. Primary therapies were: surgery 188 women (64%), radiotherapy 99 women (34%), chemotherapy two women (0.7%); four women not treated (1.3%). Complications after surgery in 25 women (13%), none were fatal. Acute or late complications after primary or postoperative radiotherapy in 39 women (25%), seven (4.6%) were late serious complications. Three women died from complications related to radiotherapy. Mean follow-up of surviving patients was 58 months. Overall disease specific five-year survival was 70%. Five-year survival in stages IA, IB, II and III was 100%, 88%, 58% and 20%, respectively. One-year survival in stage IV was 31%. Median survival in stages III and IV according to curative or palliative aim of treatment was 20 and 6 months, respectively (p<0.005). CONCLUSION: Satisfactory quality of diagnosis and therapy have been maintained through regional care for cervical cancer patients.

Adenocarcinoma↗