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1.
Adv Ecol Res ; 60: 1-24, 2019.
Article in English | MEDLINE | ID: mdl-31908359

ABSTRACT

Understanding the adaptive capacity of ecosystems to cope with change is crucial to management. However, unclear and often confusing definitions of adaptive capacity make application of this concept difficult. In this paper, we revisit definitions of adaptive capacity and operationalize the concept. We define adaptive capacity as the latent potential of an ecosystem to alter resilience in response to change. We present testable hypotheses to evaluate complementary attributes of adaptive capacity that may help further clarify the components and relevance of the concept. Adaptive sampling, inference and modeling can reduce key uncertainties incrementally over time and increase learning about adaptive capacity. Such improvements are needed because uncertainty about global change and its effect on the capacity of ecosystems to adapt to social and ecological change is high.

2.
J Environ Manage ; 213: 353-362, 2018 May 01.
Article in English | MEDLINE | ID: mdl-29502020

ABSTRACT

Scholars from many different intellectual disciplines have attempted to measure, estimate, or quantify resilience. However, there is growing concern that lack of clarity on the operationalization of the concept will limit its application. In this paper, we discuss the theory, research development and quantitative approaches in ecological and community resilience. Upon noting the lack of methods that quantify the complexities of the linked human and natural aspects of community resilience, we identify several promising approaches within the ecological resilience tradition that may be useful in filling these gaps. Further, we discuss the challenges for consolidating these approaches into a more integrated perspective for managing social-ecological systems.


Subject(s)
Ecology , Ecosystem , Humans
3.
J Clin Pathol ; 69(1): 26-34, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26188054

ABSTRACT

AIMS: The limitations of the current WHO classification of astrocytomas call for a sustained effort to improve diagnostic and prognostic accuracy. The relationship between tumour growth and clinical outcome suggests that proliferative activity should be examined. The objective of this study was to evaluate the diagnostic and prognostic value of the proliferation markers mitosin and phosphohistone H3 (pHH3) in infiltrative astrocytomas WHO grades II and III and compare the findings with mitotic count and Ki-67/MiB-1 immunostaining. METHODS: Fifty-nine and thirty-three infiltrative astrocytomas WHO grades II and III, respectively, were immunostained with the proliferation markers mitosin and pHH3 using standard immunohistochemical procedures. The expression was quantified as a proliferative index (PI) and statistically evaluated with Spearman's rank correlation test, Wilcoxon-Mann-Whitney U test, and univariable and multivariable COX regression survival analyses. RESULTS: Significant positive correlations were found between these proliferation markers. The number of mitoses, pHH3 mitotic figures (MFs), the Ki-67/MiB-1 PI and the mitosin PI were greater in WHOgrade III anaplastic astrocytomas compared to WHO grade II diffuse astrocytomas, while pHH3 PI only showed a trend. All proliferation markers were associated with poorer prognosis, but mitotic count was not. Ki-67/MiB-1, mitosin and pHH3 MF achieved statistical significance in the univariable analyses of both time to relapse (TTR) and overall survival (OS). Only mitosin remained significant in both multivariable analyses. pHH3 was significant in the multivariable analysis of OS but not of TTR. Clinical factors including age, extent of surgical resection and WHO performance status were also significantly correlated with survival. CONCLUSIONS: In conclusion, mitosin and pHH3 immunostaining have prognostic and diagnostic value in the clinical assessment of patients with infiltrative astrocytomas. The inclusion of proliferation markers in a layered diagnosis should be considered in the upcoming revision of the WHO classification system.


Subject(s)
Astrocytoma/chemistry , Biomarkers, Tumor/analysis , Brain Neoplasms/chemistry , Chromosomal Proteins, Non-Histone/analysis , Histones/analysis , Microfilament Proteins/analysis , Adult , Aged , Astrocytoma/classification , Astrocytoma/mortality , Astrocytoma/pathology , Astrocytoma/therapy , Brain Neoplasms/classification , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Cell Proliferation , Disease Progression , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Ki-67 Antigen/analysis , Male , Middle Aged , Mitosis , Mitotic Index , Multivariate Analysis , Neoplasm Grading , Neoplasm Recurrence, Local , Phosphorylation , Proportional Hazards Models , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Young Adult
4.
Br J Cancer ; 109(6): 1467-75, 2013 Sep 17.
Article in English | MEDLINE | ID: mdl-23963145

ABSTRACT

BACKGROUND: The palliative role of chemoradiation in the treatment of patients with locally advanced, inoperable non-small-cell lung cancer stage III and negative prognostic factors remains unresolved. METHODS: Patients not eligible for curative radiotherapy were randomised to receive either chemoradiation or chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the chemoradiation arm also received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. The primary end point was overall survival; secondary end points were health-related quality of life (HRQOL) and toxicity. RESULTS: Enrolment was terminated due to slow accrual after 191 patients from 25 Norwegian hospitals were randomised. Median age was 67 years and 21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median overall survival was 9.7 and 12.6 months, respectively (P<0.01). One-year survival was 34.0% and 53.2% (P<0.01). Following a minor decline during treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in the chemotherapy arm reported gradual deterioration during the subsequent months. In the chemoradiation arm, there were more hospital admissions related to side effects (P<0.05). CONCLUSION: Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Palliative Care/methods , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Female , Humans , Male , Middle Aged , Neoplasm Staging , Norway , Prognosis , Quality of Life , Survival Analysis , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
5.
Br J Cancer ; 107(3): 442-7, 2012 Jul 24.
Article in English | MEDLINE | ID: mdl-22759880

ABSTRACT

BACKGROUND: Platinum-based doublet chemotherapy is the standard first-line treatment for advanced non-small cell lung cancer (NSCLC), but earlier studies have suggested that non-platinum combinations are equally effective and better tolerated. We conducted a national, randomised study to compare a non-platinum with a platinum combination. METHODS: Eligible patients had stage IIIB/IV NSCLC and performance status (PS) 0-2. Patients received up to three cycles of vinorelbine 60 mg m(-2) p.o.+gemcitabine 1000 mg m(-2) i.v. day 1 and 8 (VG) or vinorelbine 60 mg m(-2) p.o. day 1 and 8+carboplatin area under the curve=5 (Calvert's formula) i.v. day 1 (VC). Patients ≥75 years received 75% of the dose. Endpoints were overall survival, health-related quality of life (HRQoL), toxicity, and the use of radiotherapy. RESULTS: We randomised 444 patients from September 2007 to April 2009. The median age was 65 years, 58% were men and 25% had PS 2. Median survival was VG: 6.3 months; VC: 7.0 months, P=0.802. Vinorelbine plus carboplatin patients had more grade III/IV nausea/vomiting (VG: 4%, VC: 12%, P=0.008) and grade IV neutropenia (VG: 7%, VC: 19%, P<0.001). Infections, HRQoL and the use of radiotherapy did not differ significantly between the treatment groups. CONCLUSION: The two regimens yielded similar overall survival. The VG combination had only a slightly better toxicity profile.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Female , Follow-Up Studies , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Quality of Life , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/analogs & derivatives , Vinorelbine , Gemcitabine
6.
J Neurol Surg A Cent Eur Neurosurg ; 73(2): 73-8, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22467479

ABSTRACT

BACKGROUND: Numerous observational studies indicate that more aggressive resection may prolong survival in glioblastoma patients. In Trondheim, Norway, intraoperative 3D ultrasound has been in increasing use since November 1997. The aim of the present study was to examine if the introduction of 3D ultrasound and neuronavigation (i. e., the SonoWand® system) may have had an impact on overall survival. PATIENTS/MATERIAL AND METHODS: Patient data were obtained retrospectively for the 192 glio-blastoma patients who received surgery and postoperative radiotherapy between 1990 and 2005. Overall survival, before and after 1997, was compared using the log rank test. Possible confounders were adjusted for in a multivariate Cox regression analysis. RESULTS: We observed an increase in survival for patients in the last study period (9.6 vs. 11.9 months; HR = 0.7; p = 0.034). The significant improvement in the latest time period was sustained after adjusting for age, WHO performance status (≥2) and type of radiotherapy (normofractioned or hypofractioned), and chemotherapy (yes/no), p = 0.034. 10 out of 14 patients who survived more than 3 years received treatment after the implementation of 3D ultrasound. CONCLUSION: Our study demonstrates that survival has improved within the same period that intraoperative ultrasound and neuronavigation was introduced and established in our department. The demonstrated association is a necessity for causation, but given the nature of this study, one must be cautious to claim causality. The improvement was, however, significant after adjustment for known major prognostic factors.


Subject(s)
Brain Neoplasms/surgery , Echoencephalography/methods , Glioblastoma/surgery , Imaging, Three-Dimensional/methods , Neuronavigation/methods , Neurosurgical Procedures/methods , Adult , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/mortality , Echoencephalography/instrumentation , Female , Glioblastoma/diagnostic imaging , Glioblastoma/mortality , Humans , Male , Middle Aged , Neurosurgical Procedures/mortality , Retrospective Studies , Survival Rate/trends , Treatment Outcome
7.
Clin Neuropathol ; 30(6): 301-6, 2011.
Article in English | MEDLINE | ID: mdl-22011735

ABSTRACT

INTRODUCTION: Astroblastoma is a rare glial tumor of uncertain origin affecting mostly children, adolescents and young adults. Given the rarity and the definitional problems concerning this tumor entity, the prognosis and appropriate treatment are at this point unclear. CASE REPORT: A 50-yearold Caucasian female presented with a seizure. Radiological findings showed a welldefined circumscribed tumor located in the right cerebral frontal lobe. The patient underwent primary surgery followed by postoperative radiotherapy. After 6 months the tumor recurred with multiple small lesions not available for surgery. Chemotherapy was administered with complete radiological response. Seven years after surgery and more than 6 years after completed chemotherapy the patient is free of disease. Histopathology revealed a gliomatous tumor with gemistocyte-like tumor cells arranged in palisades or strings and areas with perivascular pseudorosettes, consistent with astroblastoma. Immunophenotype and ultrastructural findings confirmed the diagnosis and verified the neuroepithelial origin. CONCLUSION: Astroblastomas are rare brain tumors and pose a challenge in the diagnostic and clinical approach. In general, they have an unpredictable course with a tendency of recurrence. This and other case reports support a survival benefit of chemotherapy, suggesting this as an important treatment option for these patients.


Subject(s)
Brain Neoplasms , Neoplasms, Neuroepithelial , Frontal Lobe , Glioma , Humans , Magnetic Resonance Imaging , Seizures
8.
Clin Exp Allergy ; 39(8): 1199-208, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19486032

ABSTRACT

BACKGROUND: House dust mites (HDM) are well-known as a source of indoor aeroallergens and for causing allergic airway diseases. Some proteolytic HDM allergens are known to activate respiratory epithelial cells to produce pro-inflammatory mediators, while there is limited knowledge regarding such activity among non-proteolytic HDM allergens. OBJECTIVE: To investigate whether Der p 2, a major non-proteolytic allergen of Dermatophagoides pteronyssinus, activates respiratory epithelial cells to produce mediators involved in asthma pathogenesis and to elucidate the mechanism of such activation. METHODS: The human bronchial epithelial cell line BEAS-2B, normal human bronchial epithelial (NHBE) cells and the alveolar epithelial cell line A549 were exposed to recombinant Der p 2. Following exposure, we analysed a panel of soluble mediators and cell adhesion receptors involved in asthma pathogenesis by promoting recruitment, survival and binding of inflammatory cells. The involvement of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) was studied using specific inhibitors. RESULTS: Der p 2 activated bronchial BEAS-2B and NHBE cells, but not alveolar A549 cells. In BEAS-2B cells Der p 2 induced dose-dependent up-regulation in both mRNA level and protein secretion of granulocyte-macrophage colony-stimulating factor, IL-6, IL-8, monocyte-chemotactic protein-1 and macrophage inflammatory protein-3alpha. Secretion as well as surface expression of intercellular adhesion molecule (ICAM)-1 was also up-regulated, which was associated with increased adhesion of monocytes to the epithelial cells. The release of cytokines and chemokines was regulated by NF-kappaB and MAPK activation in different ways, while expression of ICAM-1 was solely dependent on NF-kappaB activation. CONCLUSION: These results show that Der p 2 activates respiratory epithelial cells, indicating that this non-proteolytic allergen, in addition to its immunogenic properties, can aggravate respiratory airway disease by adjuvant-like activation of the lung epithelium.


Subject(s)
Antigens, Dermatophagoides/immunology , Bronchi/immunology , Epithelial Cells/immunology , Mitogen-Activated Protein Kinases/immunology , NF-kappa B/immunology , Animals , Arthropod Proteins , Asthma/immunology , Asthma/physiopathology , Bronchi/cytology , Cells, Cultured , Chemokine CCL2/metabolism , Chemokine CCL20/metabolism , Dermatophagoides pteronyssinus/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Intercellular Adhesion Molecule-1/biosynthesis , Interleukin-6/metabolism , Interleukin-8/metabolism , RNA, Messenger/immunology , Signal Transduction/immunology , Up-Regulation/immunology
9.
J Eur Acad Dermatol Venereol ; 23(1): 58-66, 2009 Jan.
Article in English | MEDLINE | ID: mdl-18803580

ABSTRACT

BACKGROUND: Long-term follow-up data are needed to evaluate treatment effect after photodynamic therapy (PDT). OBJECTIVE: To investigate long-term clinical, histological and cosmetic follow-up results in basal cell carcinoma (BCC) after PDT, including treatment response related to patients and lesion characteristics. MATERIALS AND METHODS: A longitudinal study of 44 patients with 60 histologically verified BCC tumours, treated with one or two sessions of dimethylsulfoxide (DMSO)-supported 5-aminolaevulinic acid--PDT following curettage, was performed. Lesions in complete remission after 3 months were followed with clinical inspection, histological investigation and evaluation of cosmetic outcome at regular intervals; long-term efficacy assessed as verified recurrence within 72 months after PDT. RESULTS: Complete remission at 3 months was achieved in 55 lesions from 39 patients. Two patients with one lesion each died. At 72 months, 43 of 53 lesions remained disease-free (81%); 68% remained after one treatment session, and 91% remained after two treatment sessions. Recurrence of tumour occurred at 6, 12, 24 and 36 months in 2, 4, 2 and 2 lesions, respectively; clinical investigation identified 97% of them. Male sex and H-mid-face zone were significantly associated with recurrence. The cosmetic outcome at 72 months was rated as good or excellent by patients and investigators in more than 90% of evaluated cases. CONCLUSION: DMSO-PDT following curettage is an effective treatment for BCC, with favourable long-term clinical, histopathological and cosmetic results. Clinical examination of treated lesions appears to be sufficient for long term follow up.


Subject(s)
Aminolevulinic Acid/therapeutic use , Carcinoma, Basal Cell/drug therapy , Dimethyl Sulfoxide/therapeutic use , Photochemotherapy , Skin Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/pathology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Remission Induction , Skin Neoplasms/pathology
10.
Thorax ; 63(10): 866-71, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18390631

ABSTRACT

BACKGROUND: To investigate whether the introduction of modern third-generation chemotherapy was associated with survival benefits in a national population of patients with advanced non-small cell lung cancer (ANSCLC) and to explore geographical and temporary variations in the utilisation of chemotherapy. METHODS: All patients with ANSCLC in the Cancer Registry of Norway during 1994-2005 were included. Using sales of vinorelbine as an indicator for chemotherapy, annual county utilisation rates were calculated. Survival before and after the general introduction of vinorelbine and associations between survival and variations in utilisation in counties were investigated. In a subgroup, the predictors of having received chemotherapy were explored. RESULTS: Of 24 875 registered patients with lung cancer, 13 757 had ANSCLC. The annual utilisation of the indicator drug in Norway increased from 3.7 to 184.2 g (1998-2005). Median survival increased from 149 to176 days (p<0.001). The adjusted hazard ratio (HR) for a diagnosis after the introduction was 0.93 (95% CI 0.88 to 0.99). County utilisation rates of vinorelbine (increments of 100 mg/1000 inhabitants) were inversely associated with the risk of death (HR 0.84, 95% CI 0.73 to 0.98). County of residence predicted chemotherapy utilisation with odds ratios in the range 0.13 (95% CI 0.1 to 0.19) to 1.04 (95% CI 0.64 to 1.69), a county with traditionally high utilisation as reference. CONCLUSION: Utilisation of third-generation chemotherapy was associated with slightly increased survival of patients with ANSCLC. Geographical and temporal differences in utilisation indicate variable quality of delivered care.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Drug Utilization Review , Female , Humans , Lung Neoplasms/mortality , Male , Norway/epidemiology , Survival Analysis , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine
11.
Br J Cancer ; 97(3): 283-9, 2007 Aug 06.
Article in English | MEDLINE | ID: mdl-17595658

ABSTRACT

This randomised phase III study in advanced non-small cell lung cancer (NSCLC) patients was conducted to compare vinorelbine/carboplatin (VC) and gemcitabine/carboplatin (GC) regarding efficacy, health-related quality of life (HRQOL) and toxicity. Chemonaive patients with NSCLC stage IIIB/IV and WHO performance status 0-2 were eligible. No upper age limit was defined. Patients received vinorelbine 25 mg m(-2) or gemcitabine 1000 mg m(-2) on days 1 and 8 and carboplatin AUC4 on day 1 and three courses with 3-week cycles. HRQOL questionnaires were completed at baseline, before chemotherapy and every 8 weeks until 49 weeks. During 14 months, 432 patients were included (VC, n=218; GC, n=214). Median survival was 7.3 vs 6.4 months, 1-year survival 28 vs 30% and 2-year survival 7 vs 7% in the VC and GC arm, respectively (P=0.89). HRQOL, represented by global QOL, nausea/vomiting, dyspnoea and pain, showed no significant differences. More grade 3-4 anaemia (P<0.01), thrombocytopenia (P<0.01) and transfusions of blood (P<0.01) or platelets (P<0.01) were observed in the GC arm. There was more grade 3-4 leucopoenia (P<0.01) in the VC arm, but the rate of neutropenic infections was the same (P=0.87). In conclusion, overall survival and HRQOL are similar, while grade 3-4 toxicity requiring interventions are less frequent when VC is compared to GC in advanced NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Humans , Male , Middle Aged , Quality of Life , Survival Analysis , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine , Gemcitabine
12.
Br J Cancer ; 95(8): 966-73, 2006 Oct 23.
Article in English | MEDLINE | ID: mdl-17047644

ABSTRACT

This randomised multicentre trial was conducted to establish the optimal duration of palliative chemotherapy in advanced non-small-cell lung cancer (NSCLC). We compared a policy of three vs six courses of new-generation platinum-based combination chemotherapy with regard to effects on quality of life (QoL) and survival. Patients with stage IIIB or IV NSCLC and WHO performance status (PS) 0-2 were randomised to receive three (C3) or six (C6) courses of carboplatin (area under the curve (AUC) 4, Chatelut's formula, equivalent to Calvert's AUC 5) on day 1 and vinorelbine 25 mg m(-2) on days 1 and 8 of a 3-week cycle. Key end points were QoL at 18 weeks, measured with EORTC Quality of Life Questionnaire (QLQ)-C30 and QLQ-LC13, and overall survival. Secondary end points were progression-free survival and need of palliative radiotherapy. Two hundred and ninety-seven patients were randomised (C3 150, C6 147). Their median age was 65 years, 30% had PS 2 and 76% stage IV disease. Seventy-eight and 54% of C3 and C6 patients, respectively, completed all scheduled chemotherapy courses. Compliance with QoL questionnaires was 88%. There were no significant group differences in global QoL, pain or fatigue up to 26 weeks. The dyspnoea palliation rate was lower in the C3 arm at 18 and 26 weeks (P<0.05), but this finding was inconsistent across different methods of analysis. Median survival in the C3 group was 28 vs 32 weeks in the C6 group (P=0.75, HR 1.04, 95% CI 0.82-1.31). One- and 2-year survival rates were 25 and 9% vs 25 and 5% in the C3 and C6 arm, respectively. Median progression-free survival was 16 and 21 weeks in the C3 and C6 groups, respectively (P=0.21, HR 0.86, 95% CI 0.68-1.08). In conclusion, palliative chemotherapy with carboplatin and vinorelbine beyond three courses conveys no survival or consistent QoL benefits in advanced NSCLC.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Quality of Life , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Drug Administration Schedule , Fatigue/chemically induced , Female , Follow-Up Studies , Humans , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Pain/chemically induced , Palliative Care , Surveys and Questionnaires , Survival Analysis , Survival Rate , Time Factors , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/adverse effects , Vinblastine/analogs & derivatives , Vinorelbine
13.
Clin Neuropathol ; 24(4): 170-4, 2005.
Article in English | MEDLINE | ID: mdl-16033133

ABSTRACT

Even though tumor grade, subtype, and extent of resection are strong prognostic factors in human meningiomas, the growth of this tumor is still unpredictable, and additional prognostic markers are needed. Thus, immunohistochemical determination of proliferative activity using the Ki-67 equivalent antibody MIB-1 has gained increased attention. However, the reported prognostic significance of this marker in meningiomas is not fully clarified. The aim of this study was to investigate the prognostic role of MIB-1 proliferation index (PI) in a series of meningiomas comprising 23 benign, 17 atypical, and 9 anaplastic tumors. MIB- 1 PI increased with increasing tumor grade and discriminated significantly benign from atypical and anaplastic meningiomas whereas no difference was found between the latter two grades. However, due to the considerable overlap of PI values between the various grades, one should be circumspect before using this criterion for tumor grading. Furthermore, MIB-1 PIs were significantly higher in recurrent tumors compared with non-recurrent and a reliable MIB-1 PI cut-off value of 10% was established. This value, however, cannot automatically be adapted by other laboratories and must be regarded just as a guideline. In conclusion, MIB-1 PI appears as an important prognostic factor and should be used in combination with traditional histological criteria for malignancy in order to identify meningiomas with increased risk of recurrence.


Subject(s)
Antibodies, Antinuclear/analysis , Antibodies, Monoclonal/analysis , Biomarkers, Tumor/analysis , Ki-67 Antigen/analysis , Meningeal Neoplasms/pathology , Meningioma/pathology , Neoplasm Recurrence, Local/pathology , Adult , Aged , Aged, 80 and over , Cell Proliferation , Female , Humans , Male , Meningeal Neoplasms/metabolism , Meningioma/metabolism , Middle Aged , Neoplasm Recurrence, Local/metabolism , Predictive Value of Tests , Prognosis , Statistics, Nonparametric
14.
Occup Environ Med ; 59(5): 309-22, 2002 May.
Article in English | MEDLINE | ID: mdl-11983846

ABSTRACT

OBJECTIVES: Spouses and staff of the World Bank Group (WBG) were questioned about the impact of international business travel on families and travellers. Dependent variables were self reported stress, concern about the health of the traveller, and negative impact on the family. We hypothesised that several travel factors (independent variables) would be associated with these impacts. These travel factors had to do with the frequency, duration, and predictability of travel and its interference with family activities. METHODS: Survey forms were developed and distributed to all spouses of travelling staff as well as a small sample of operational staff. Kendall's tau b correlation coefficients of response frequencies were computed with the data from scaled items. Written responses to open ended questions were categorised. RESULTS: Response rates for spouses and staff were 24% and 36%, respectively. Half the spouse sample (n=533) and almost 75% of the staff sample (n=102) reported high or very high stress due to business travel. Self reported spouse stress was associated with six out of eight travel factors. Female spouses, those with children, and younger spouses reported greater stress. Self reported staff stress was significantly associated with four out of nine travel factors. Further insight into how business travel affects families and staff (including children's behavioural changes) and how families cope was gained through responses to written questions. CONCLUSIONS: The findings support the notion that lengthy and frequent travel and frequent changes in travel dates which affect family plans, all characteristic of WBG missions, negatively affects many spouses and children (particularly young children) and that the strain on families contributes significantly to the stress staff feel about their travel. Policies or management practices that take into consideration family activities and give staff greater leeway in controlling and refusing travel may help relieve stress.


Subject(s)
Commerce , Family Health , Occupational Diseases/etiology , Stress, Psychological/etiology , Travel , Adaptation, Psychological , Adult , Affective Symptoms , Child , Female , Humans , Male , Middle Aged , Psychology, Child , Spouses , Surveys and Questionnaires
15.
J Clin Oncol ; 19(15): 3532-8, 2001 Aug 01.
Article in English | MEDLINE | ID: mdl-11481360

ABSTRACT

PURPOSE: To investigate the feasibility, efficacy, and safety of adding paclitaxel to cisplatin/etoposide chemotherapy and concurrent thoracic radiotherapy (TRT) in treatment of limited-stage small-cell lung cancer (LD-SCLC). PATIENTS AND METHODS: Patients received five courses of chemotherapy (paclitaxel 175 mg/m2 1-hour intravenous [IV] infusion day 1; cisplatin 50 mg/m(2) IV day 1; etoposide 100 mg/m2 IV day 1; oral etoposide 100 mg bid days 2 to 5) at 3-week intervals. TRT (42 Gy administered in 15 fractions) was administered concurrent with chemotherapy cycle 3. All patients were evaluated before starting TRT and 4 weeks after termination of chemotherapy. Patients achieving complete remission (CR) were administered prophylactic cranial irradiation. RESULTS: Thirty-nine patients were included, and the median age was 63 years. The median follow-up was 36 months (range, 19 to 57 months). The overall response rate was 92% (CR, 81%; partial response, 11%), and the median survival was 21 months. The 1- and 2-year disease-specific survival rates were 69% and 37%, respectively. Of 29 CR patients, 83% have relapsed. Brain metastasis was as frequent as local recurrences (42%). Hematologic toxicity included grade 3 to 4 leukopenia in 74% of patients and grade 3 thrombocytopenia in 10%. One treatment-related death occurred as a result of severe neutropenia and septicemia. Hematotoxicity caused dose reductions in 31% of courses. One patient had an anaphylactic reaction during the first paclitaxel infusion. Paclitaxel-related neuropathy and myalgia were reversible. Grade 3 esophagitis was seen in five patients during and shortly after TRT. CONCLUSION: This novel multimodal regimen is effective and well tolerated in patients with LD-SCLC. It compares favorably with previously published phase II studies.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Male , Middle Aged , Neoplasm Staging , Paclitaxel/administration & dosage , Paclitaxel/adverse effects
17.
Mol Cell Biol ; 21(7): 2594-607, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11259606

ABSTRACT

The molecular chaperone complex hsp90-p23 interacts with the dioxin receptor, a ligand-dependent basic helix-loop-helix (bHLH)/Per-Arnt-Sim domain transcription factor. Whereas biochemical and genetic evidence indicates that hsp90 is important for maintenance of a high-affinity ligand binding conformation of the dioxin receptor, the role of hsp90-associated proteins in regulation of the dioxin receptor function remains unclear. Here we demonstrate that the integrity of the hsp90 complex characterized by the presence of the hsp90-associated cochaperone p23 and additional cochaperone proteins is important for regulation of the intracellular localization of the dioxin receptor by two mechanisms. First, in the absence of ligand, the dioxin receptor-hsp90 complex was associated with the immunophilin-like protein XAP2 to mediate cytoplasmic retention of the dioxin receptor. Second, upon exposure to ligand, the p23-associated hsp90 complex mediated interaction of the dioxin receptor with the nuclear import receptor protein pendulin and subsequent nuclear translocation of the receptor. Interestingly, these two modes of regulation target two distinct functional domains of the dioxin receptor. Whereas the nuclear localization signal-containing and hsp90-interacting bHLH domain of the receptor regulates ligand-dependent nuclear import, the interaction of the p23-hsp90-XAP2 complex with the ligand binding domain of the dioxin receptor was essential to mediate cytoplasmic retention of the ligand-free receptor form. In conclusion, these data suggest a novel role of the hsp90 molecular chaperone complex in regulation of the intracellular localization of the dioxin receptor.


Subject(s)
HSP90 Heat-Shock Proteins/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Signal Transduction , Animals , Biological Transport , COS Cells , HSP90 Heat-Shock Proteins/genetics , HeLa Cells , Humans , Immunophilins/genetics , Immunophilins/metabolism , Ligands , Receptors, Aryl Hydrocarbon/genetics
18.
Qual Life Res ; 8(1-2): 25-43, 1999.
Article in English | MEDLINE | ID: mdl-10457736

ABSTRACT

This paper demonstrates how the Mokken Scaling Model and other statistical tools may be useful in assessing the consistency of psychometric properties of health-related quality of life (HRQoL) scales across various populations. The main focus is the psychometric performance of the scales proposed for the EORTC QLQ-C30 in seven patient groups totalling more than 2,000 cancer patients. All scales performed satisfactorily in the total sample with the exception of the role functioning and cognitive functioning scales, which failed in terms of reliability and item discriminant validity. The descriptive statistics for the scales show that several of them, particularly those that build upon only two items, have discrimination problems at the extremes, visible in the high percentages at the maximum or the minimum observed values. The scalability analysis in the subsamples showed that the essential assumption in the Mokken Scaling Model of equal item step order does not hold for the cognitive functioning, emotional functioning and physical functioning scales. We conclude that the Mokken Scaling Model is well suited to the purpose of examining the generalizability of HRQoL scales across subpopulations although a global statistical test of the fit of the measurement model is not available.


Subject(s)
Health Status , Health Surveys , Models, Statistical , Neoplasms/psychology , Quality of Life , Surveys and Questionnaires/standards , Activities of Daily Living , Aged , Cognition , Discriminant Analysis , Female , Humans , Male , Mental Health , Middle Aged , Neoplasms/physiopathology , Neoplasms/therapy , Norway , Psychometrics , Reproducibility of Results , Statistics, Nonparametric
19.
Tidsskr Nor Laegeforen ; 117(2): 203-7, 1997 Jan 20.
Article in Norwegian | MEDLINE | ID: mdl-9064834

ABSTRACT

About 20% of al lung cancers among men are attributable to occupational exposure. During the years 1991 through 1993, Norwegian doctors reported 161 (4.6%) of 3.510 incidents of cancer in Norwegian men to the Labour Inspection as probably caused by occupational exposure. The proportion of such assumed occupational lung cancer cases varied with geographical region from 0.7% to 6.7%. Notification of an occupational cancer can be justification for economic benefits to the patient and his/her family. The most common assumed causes of the 161 cases notified as occupational lung cancers were asbestos dust exposure (148 cases), exposure to nickel (21 cases), and exposure to stone dust containing crystalline silica (18 cases). The predominating occupations of the patients at the time of the assumed carcinogenic exposure were machinist, industrial worker in metallurgical or chemical industry, mechanic, or metal worker (metal sheet worker, welder).


Subject(s)
Air Pollutants, Occupational/adverse effects , Lung Neoplasms/chemically induced , Occupational Diseases/chemically induced , Adult , Aged , Disease Notification , Humans , Incidence , Lung Neoplasms/epidemiology , Male , Middle Aged , Norway/epidemiology , Occupational Diseases/epidemiology , Registries
20.
Eur J Cancer ; 31A(11): 1785-9, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8541101

ABSTRACT

A national multicentre study was performed to investigate the prevalent use of "alternative medicine", here called "non-proven therapies (NPT)", applied among Norwegian cancer patients. Of 911 patients invited to take part in the study, 642 were included in the analysis. Demographic characteristics were collected for all patients. The participating physicians gave information about the patients' clinical characteristics. Among 630 evaluable patients, 20% had been or were present users of NPTs for their oncological disease. The preferred methods were healing by hand and faith healing. Herbs, vitamins, diets and Iscador were other popular methods. As many as 40% of the users of NPTs had used NPTs earlier for non-malignant diseases. Elderly patients were less likely to use NPTs. Use was high in the northern part of Norway.


Subject(s)
Complementary Therapies/statistics & numerical data , Neoplasms/therapy , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Mental Healing , Middle Aged , Neoplasms/epidemiology , Norway/epidemiology , Prevalence , Sex Distribution
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