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1.
Gesundheitswesen ; 73(1): 3-12, 2011 Jan.
Article in German | MEDLINE | ID: mdl-20491005

ABSTRACT

The link between leaders' behaviour and health has only recently been the focus of scientific research and the results which already exist on this topic have, to date, not been systematically evaluated or summarized. The objective of this article is to make an attempt to provide a summarised overview of the current state of research. Subject-related databases list 42 publications dealing with the relationship between leaders' behaviour and the state of health and well-being of their employees. The literature discusses leaders' behaviour as being both a stressor (source of stress) and a resource. The publications discussed here also provide the first empirical evidence on the influence of various leadership styles on the health of the employees. In particular, transformational and employee-orientated leadership are considered to be beneficial to health. But the question of how leaders' behaviour influences health has not been satisfactorily explained. In most of the publications included, a direct link was assumed and, in the majority of cases, confirmed empirically. In addition, it also appears that there may be an indirect influence which may be moderated or mediated by, e. g., working conditions or the personality of the individual. The relatively small number of research examinations into the influence of leaders' behaviour on the health and well-being of their staff shows that there is a need for additional research.


Subject(s)
Biomedical Research/trends , Health Status , Leadership , Occupational Health , Occupational Medicine/trends , Germany
2.
Gesundheitswesen ; 72(4): 209-15, 2010 Apr.
Article in German | MEDLINE | ID: mdl-19533583

ABSTRACT

Caregivers of the residents in nursing homes are exposed to a high degree of physical and mental stress. The first part of this article deals with the development and evaluation of an intervention programme aiming at the staff's qualification to deal with these stresses. The main purpose of the programme was the improvement of the caregiver's methodical, social and self-care competences. A controlled study design was applied to evaluate the training effects. Seventeen homes for the elderly and nursing homes were involved in the pilot study. All participants of the intervention group (eleven homes) assessed their competences, their job conditions and their mental health status at the beginning and at the end of the training. The participants of the control group (six homes) assessed these aspects at the same time, but had no training in between. Furthermore, the intervention group took part in a third survey about twelve weeks after the intervention had been finished. Among the training participants, particularly the self-care skills improved (p=0.01). In addition, occupational stress could be reduced (p=0.01) and the climate with the residents enhanced (p=0.06). Compared to the changes also observed in the control group, statistically significant effects only confined to the change of the climate with the residents (p=0.01). In sum, the evaluation confirms the programme's success to develop the caregiver's professional competences in order to reduce their job stress. Further follow-up-studies are needed to investigate the long-term influence of behavioural prevention programmes like this on employee's health.


Subject(s)
Alzheimer Disease/nursing , Health Care Reform , Health Promotion , Homes for the Aged , Inservice Training , Nursing Homes , Occupational Diseases/prevention & control , Staff Development , Stress, Psychological/complications , Stress, Psychological/prevention & control , Workplace , Adaptation, Psychological , Aged , Alzheimer Disease/psychology , Cooperative Behavior , Follow-Up Studies , Germany , Health Services Accessibility , Humans , Interdisciplinary Communication , Occupational Diseases/psychology , Outcome and Process Assessment, Health Care , Pilot Projects , Program Evaluation , Self Care , Workload/psychology
3.
Gesundheitswesen ; 72(4): 216-21, 2010 Apr.
Article in German | MEDLINE | ID: mdl-19492281

ABSTRACT

This article is a follow-on from the first article on the development and evaluation of an intervention programme aiming to teach the staff of care facilities how to better deal with the mental strain they are exposed to. After a brief review of the programme's goal of 'increasing in-house health through staff development' and of the pilot study, this report initially shows how the findings from the pilot phase have been integrated into the original programme and what modifications have been carried out. For example, elements that proved to be successful such as the setting up of a 'steering circle' have been kept and, in addition, solutions for acknowledged weak points such as the insufficient transfer of the acquired knowledge to everyday work situations have been developed. In order to adequately support health care facilities during the implementation of the programme, additional courses to train multipliers who are to offer the necessary assistance, were carried out. The article also covers the evaluation of the quality of the development programme and of the accompanying implementation of the programme by the multipliers. At the end, a practical example is used to illustrate the issue and to demonstrate what actual shape the implementation at the different facilities can take.


Subject(s)
Alzheimer Disease/nursing , Health Care Reform , Health Promotion , Homes for the Aged , Inservice Training , Nursing Homes , Occupational Diseases/prevention & control , Staff Development , Stress, Psychological/complications , Stress, Psychological/prevention & control , Transfer, Psychology , Workplace , Aged , Alzheimer Disease/psychology , Cooperative Behavior , Germany , Health Plan Implementation , Humans , Interdisciplinary Communication , Occupational Diseases/psychology , Pilot Projects , Program Evaluation
4.
Tumour Biol ; 24(3): 109-15, 2003.
Article in English | MEDLINE | ID: mdl-14610314

ABSTRACT

Colorectal cancer is a major cause of death in Europe and the USA, and much effort is therefore devoted to improve its early detection. In this article, we report the abnormal expression of gastric mucin in aberrant crypt foci (ACF) that appear in the colon mucosae removed from colorectal cancer patients and rats treated with methyl-N'-nitro-N-nitroso-guanidine (MNNG). We performed the immunoperoxidase test using monoclonal antibodies raised against gastric M1 mucin encoded by the MUC5AC gene and against rat gastric mucins (MAb 660), respectively. In both human and rat colon, these anti-gastric mucin MAbs stained specifically goblet cells within ACF. In humans, the M1/MUC5AC mucin was expressed in the upper part of the glands in hyperplastic ACF and in the typical ACF. In addition, the anti-gastric mucin MAbs stained some rare, scattered, histologically normal glands in the human and rat colon mucosae. These glands may be regarded as precursors of ACF. The abnormal expression of the MUC5AC gene constitutes a novel change in addition to genetic modifications already observed in ACF, and supports our previous findings demonstrating the potential of this gastric mucin as an early marker of human and rat colon carcinogenesis.


Subject(s)
Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Gastric Mucins/biosynthesis , Gastric Mucosa/metabolism , Precancerous Conditions/metabolism , Animals , Antibodies, Monoclonal/metabolism , Carcinogens , Cell Transformation, Neoplastic , Colon/metabolism , Colon/pathology , Humans , Immunohistochemistry , Methylnitronitrosoguanidine , Rats
5.
Oncogene ; 21(44): 6740-50, 2002 Oct 03.
Article in English | MEDLINE | ID: mdl-12360401

ABSTRACT

Bile acids are implicated in colorectal carcinogenesis as evidenced by epidemiological and experimental studies. We examined whether bile acids stimulate cellular invasion of human colorectal and dog kidney epithelial cells at different stages of tumor progression. Colon PC/AA/C1, PCmsrc, and HCT-8/E11 cells and kidney MDCKT23 cells were seeded on top of collagen type I gels and invasive cells were counted after 24 h incubation. Activation of the Rac1 and RhoA small GTPases was investigated by pull-down assays. Haptotaxis was analysed with modified Boyden chambers. Lithocholic acid, chenodeoxycholic acid, cholic acid and deoxycholic acid stimulated cellular invasion of SRC- and RhoA-transformed PCmsrc and MDCKT23-RhoAV14 cells, and of HCT-8/E11 cells originating from a sporadic tumor, but were ineffective in premalignant PC/AA/C1 and MDCKT23 cells. Bile acid-stimulated invasion occurred through stimulation of haptotaxis and was dependent on the RhoA/Rho-kinase pathway and signaling cascades using protein kinase C, mitogen-activated protein kinase, and cyclooxygenase-2. Accordingly, BA-induced invasion was associated with activation of the Rac1 and RhoA GTPases and expression of the farnesoid X receptor. We conclude that bile acids stimulate invasion and haptotaxis in colorectal cancer cells via several cancer invasion signaling pathways.


Subject(s)
Bile Acids and Salts/pharmacology , Colorectal Neoplasms/pathology , Genes, src/physiology , rhoA GTP-Binding Protein/physiology , Cyclooxygenase 2 , Dose-Response Relationship, Drug , Guanosine Triphosphate/metabolism , Humans , Integrin beta1/physiology , Isoenzymes/physiology , Membrane Proteins , Neoplasm Invasiveness , Phosphatidylinositol 3-Kinases/physiology , Precancerous Conditions/pathology , Prostaglandin-Endoperoxide Synthases/physiology , Tumor Cells, Cultured
6.
Z Gerontol Geriatr ; 34(5): 401-7, 2001 Oct.
Article in German | MEDLINE | ID: mdl-11718103

ABSTRACT

Caregivers of the residents in nursing homes are exposed to a high degree of physical and mental stress. The purpose of this study was to develop and to test the effects of skill training aimed at reducing occupational stress. The training consisting of 12 sessions of 90 minutes each was designed for nursing assistants and for care supervisors, respectively. Contents of the program are communicating with the demented, coping with job stress and cooperating with colleagues and subordinates, respectively. Eleven homes for the elderly and nursing homes were involved in the pilot study; 88 caregivers participated in the training, 34 of them were supervisors and 54 nursing assistants. The participants mainly appreciated the contents of the training. A controlled study design was applied to evaluate the training effects. 56 participants assessed their competencies, their job conditions and their health status at the beginning, at the end of the training as well as 12 weeks after the intervention had been finished. 56 persons completed the questionnaire receiving no training. Among the training participants, particularly the self-care skills improved. In addition, occupational stress could be reduced and the climate with the residents improved significantly, whereas the frequency of health problems did not change. Compared to the changes also observed in the control group, statistically significant effects were confined to the improvement of the climate with the residents. Care supervisors in general reported a higher benefit from the training than did nursing assistants. The results of the pilot study were used to adapt the training to the caregivers' needs.


Subject(s)
Geriatric Nursing/education , Homes for the Aged/organization & administration , Inservice Training , Nursing Homes/organization & administration , Patient Care Team , Stress, Psychological/complications , Workload/psychology , Adaptation, Psychological , Adult , Aged , Burnout, Professional/prevention & control , Burnout, Professional/psychology , Communication , Curriculum , Female , Germany , Health Promotion , Humans , Interprofessional Relations , Male , Middle Aged
7.
Mutat Res ; 480-481: 359-69, 2001 Sep 01.
Article in English | MEDLINE | ID: mdl-11506828

ABSTRACT

Bile acids play a role in colorectal carcinogenesis as evidenced by epidemiological and experimental studies. Some bile acids stimulate growth of normal colonic and adenoma cells, but not of colorectal cancer cells. Moreover, bile acids stimulate invasion of colorectal cancer cells, at least in vitro. One possible mechanism of action is bile acid-induced DNA binding and transactivation of the activator protein-1 (AP-1) by co-operate activation of extracellular signal-regulated kinases (ERKs) and PKC signaling. In the present paper, we review the mechanisms by which bile acids influence carcinogenesis.


Subject(s)
Bile Acids and Salts/toxicity , Cell Transformation, Neoplastic/chemically induced , Colorectal Neoplasms/chemically induced , Colorectal Neoplasms/epidemiology , Animals , Bile Acids and Salts/metabolism , Cell Division/drug effects , DNA/metabolism , Humans , Neoplasm Invasiveness , Signal Transduction/drug effects , Transcription Factor AP-1/metabolism , Transcriptional Activation/drug effects
9.
Biochem Biophys Res Commun ; 272(2): 513-8, 2000 Jun 07.
Article in English | MEDLINE | ID: mdl-10833444

ABSTRACT

Previously we have demonstrated a reciprocal deregulation of various homeobox genes (HOXB6, B8, C8 and C9 vs Cdx-1) in human colorectal cancer (CRC). In the present study, using RT-PCR, we have investigated the expression pattern of these homeobox genes in various human colon cell lines, representing various stages of colon cancer progression and differentiation. Thus, we have tested polyposis coli Pc/AA adenoma cells, Caco-2, HT-29 and LS174T adenocarcinoma cell lines. All cell lines, except LS174T, demonstrated a pattern of deregulated homeobox gene expression which resembled that of CRC. In contrast, the pattern of expression of these genes in the highly oncogenic LS174T cells, as well as in Caco-2 cells transfected with activated Ha-ras or Polyoma middle T oncogene, resembled that of the normal mucosa. The reciprocal deregulation of HOX and Cdx-1 genes in CRC and in CRC-derived cell lines suggests a possible role in human CRC development.


Subject(s)
Colonic Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , Genes, Homeobox/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adenomatous Polyposis Coli/metabolism , Adenomatous Polyposis Coli/pathology , Butyric Acid/pharmacology , Cell Count , Cell Differentiation/drug effects , Colonic Neoplasms/pathology , Disease Progression , Gene Expression Regulation, Neoplastic/drug effects , Homeodomain Proteins/genetics , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Tumor Cells, Cultured
10.
Cancer Res ; 60(3): 672-8, 2000 Feb 01.
Article in English | MEDLINE | ID: mdl-10676652

ABSTRACT

Bile acids were shown previously to inhibit proliferation and to induce monocytic differentiation in HL60 human acute promyelocytic leukemia cells (A. Zimber et al., Int. J. Cancer, 59: 71-77, 1994). In this report, we hypothesized that bile acids may exert a positive cooperativity with two known inducers of leukemic cell differentiation, all-trans retinoic acid and 1,25(OH)2-vitamin D3. Our results provide evidence that bile acids induced the monocytic differentiation of HL60 and THP-1 human leukemia cells exposed to ineffective concentrations of these inducers. The protein kinase C (PKC) inhibitors H-7 (10 and 20 microM) and staurosporine (5 and 20 nM) modulated the effects of bile acids on HL60 cell differentiation. Most interestingly, bile acids are shown herein to down-regulate the expression of the serine protease myeloblastin gene involved in the differentiation of myeloid hematopoietic cells. In agreement with the recent identification of nuclear receptors for bile acids, our data suggest that functional interactions between nuclear bile acid signaling pathways, PKC, and nuclear receptors for retinoic acid and vitamin D3 are involved in the down-regulation of the myeloblastin gene and the induction of cell differentiation in human leukemic cells.


Subject(s)
Bile Acids and Salts/pharmacology , Calcitriol/pharmacology , Gene Expression Regulation/drug effects , Monocytes/drug effects , Serine Endopeptidases/genetics , Tretinoin/pharmacology , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , Cell Cycle/drug effects , Cell Differentiation/drug effects , Cell Division/drug effects , Down-Regulation , HL-60 Cells , Humans , Monocytes/cytology , Myeloblastin , Protein Kinase C/antagonists & inhibitors , Tetradecanoylphorbol Acetate/pharmacology
11.
Z Gerontol Geriatr ; 32(5): 348-57, 1999 Oct.
Article in German | MEDLINE | ID: mdl-10552173

ABSTRACT

Falls can result in physical injuries as well as anxieties about falling and decreases in physical activities. For elderly osteoporotic people falls are a serious problem. In the progression of impairment the loss of bone density decreases the resistance of bone structure. Prevention of falls is therefore an important task for patients with osteoporosis. Numerous studies document the positive effects of physical activities and exercise on muscular strength, on balance, and gait; other studies focussed on the efficacy of intervention programs in consideration of the use of medication. But the studies did not consider the specific situation of osteoporotic people. In our study we focussed on the strengthening of sensorimotor functions, which can be expected in a short period of time and may therefore motivate for long-term intervention programs to increase bone density. This program was applied to a sample of 42 osteoporotic women with an average age of 66 participating in a training program for 90 minutes once a week over a period of 10 weeks. The effectiveness of the program was assessed by a battery including differential sensorimotor functions. Regarding the initial test results, there were only small differences between the study sample and a control group tested with the identical assessment. We used a pre-post-training design which enabled us to control the effects of the training program. Sensorimotor functions were tested three times: 3 months before the program started, at the beginning and at the end of the intervention program. The significant improvements from the first to the second testing were most likely due to repeated measurement. Further significant improvements, measured at the end of the program, can be interpreted as effects of the training. We conclude that sensorimotor functions of elderly with osteoporosis could be trained effectively in a rather short time.


Subject(s)
Accidental Falls/prevention & control , Osteoporosis, Postmenopausal/rehabilitation , Physical Therapy Modalities , Aged , Bone Density/physiology , Female , Follow-Up Studies , Geriatric Assessment , Humans , Middle Aged , Osteoporosis, Postmenopausal/physiopathology , Treatment Outcome
12.
Int Arch Occup Environ Health ; 72(4): 205-14, 1999 Jul.
Article in English | MEDLINE | ID: mdl-10491774

ABSTRACT

OBJECTIVES: The main aim of the study was to examine possible solvent-associated effects on the nervous system in currently employed painters. Special attention was paid to evaluate subtle health effects. MATERIALS AND METHODS: A total of 401 painters and 209 construction workers without solvent exposure with at least 10 years of professional experience were subjected to a clinical, neurological, psychiatric, neuropsychological and neurophysiological examination. For personal medical and occupational history, standardized questionnaires were used. A quantitative rating of exposure was obtained by expert rating of the respective occupational history without knowledge of the individual test results. RESULTS: There was no excess of somatic disorders or solvent-associated adverse effects on the nervous system. No distinct effects of solvent exposure on nerve conduction velocities (NCV) or cognition were found. Discrete NCV deficits in painters were not considered a sign of subclinical polyneuropathy. Painters, however, reported an excess of specific symptoms that could be assigned to "mood and behaviour". The differences between specific and non-specific questionnaire outcomes on the one hand and the positive correlation between chronic exposure index and symptom scores on the other hand support the hypothesis of solvent-induced effects. Because data is lacking on past solvent exposure, it is not possible to relate these effects to current exposure limits. CONCLUSIONS: Currently employed painters differ from controls not exposed to solvents with respect to the frequency of certain symptoms in mood and behaviour. These symptoms are related to life-long solvent exposure rather than to current exposure. At present, the issue of time course and reversibility or irreversibility of these symptoms cannot be answered. The predictive value for subsequent neuropsychiatric morbidity remains to be elucidated in follow-up studies.


Subject(s)
Occupational Health , Construction Materials , Cross-Sectional Studies , Humans , Occupational Exposure , Paint
13.
Aust N Z J Psychiatry ; 33(6): 825-30, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10619208

ABSTRACT

OBJECTIVE: This study aims to determine the prevalence of alcohol problems among residents in old age homes, its demographic and clinical features, and its association with the risk of falling. METHOD: All residents (n = 1922) living in 20 randomly selected residential and nursing homes in the city of Mannheim, Germany, were included. Based on routine documentation, details of their sociodemographic features, medical diagnoses made upon admission, and current medication were compiled. The home staff filled out for each resident a standardised assessment sheet on activities of daily living-impairment (Barthel Index), behaviour problems, alcohol consumption, and frequency of falls. RESULTS: According to the diagnoses of the primary care physicians, 7.4% of the residents had mental and behavioural disorders due to alcohol (ICD-10: F10). Rates were particularly high among men, and younger and single or divorced residents. A high percentage of those with a diagnosis of alcohol abuse/dependence (41.1%) were transferred from mental hospitals. Home staff reported current alcohol abuse/dependence among 3.4% of all residents. The risk of falling was significantly elevated (Odds ratio: 2.65; p<0.01) among those with current alcohol problems. CONCLUSION: The results corroborate the findings from other studies wherein residents of old age homes constitute a group at risk of alcohol abuse and dependence. Alcohol problems were more the cause for, rather than the consequence of, home admission.


Subject(s)
Alcohol-Related Disorders/epidemiology , Homes for the Aged/statistics & numerical data , Nursing Homes/statistics & numerical data , Urban Population/statistics & numerical data , Accidental Falls/prevention & control , Accidental Falls/statistics & numerical data , Aged , Alcohol-Related Disorders/diagnosis , Alcohol-Related Disorders/psychology , Alcoholism/diagnosis , Alcoholism/epidemiology , Alcoholism/psychology , Cross-Sectional Studies , Female , Germany/epidemiology , Humans , Incidence , Male , Odds Ratio , Risk
15.
Gesundheitswesen ; 60(4): 239-46, 1998 Apr.
Article in German | MEDLINE | ID: mdl-9617011

ABSTRACT

Residents in homes for the elderly and in nursing homes suffer from physical and mental disorders that are prevalent far above average. In the course of the changes that are presently taking place in the German health care system there is now an increase in the number of mentally ill and severely impaired persons residing in old-age homes. Earlier epidemiological studies do not yield any conclusive predictions of changes in residential structures and hence in nursing care requirements. Two cross-sectional studies are presented on the prevalence of physical and mental diseases, daily and behaviour problems among residents of old-age and nursing homes in Mannheim. There was a distinct increase in average age, functional impairment, depression and disoriented behaviour among residents in 12 homes for the elderly in Mannheim conducted in 1988 (n = 542) and 1992 (n = 497). During the period it was noted that disoriented behaviour significantly increased the mortality risk. In another study the by far larger group of nursing home residents was investigated. So far we have data for 1995 and 1996 on results obtained from 1178 residents of Mannheim homes for the elderly and nursing homes. Among the residents of nursing homes there was a much higher prevalence of functional impairment and behaviour problems than among those of homes for the elderly. Despite a very high prevalence of depression or disorientation, only every third resident was diagnosed as suffering from organic brain disease and only every tenth resident had a depressive disorder. Since a growing proportion of residents will be mentally ill or severely impaired, these institutions will be facing increasing medical and nursing demands. Due to limited resources, the homes cannot meet these demands adequately. Hence, health policy changes are mandatory to improve nursing care and to avoid placing an increasing burden on the nursing staff.


Subject(s)
Activities of Daily Living/classification , Dementia/epidemiology , Disabled Persons/statistics & numerical data , Frail Elderly/statistics & numerical data , Homes for the Aged/statistics & numerical data , Nursing Homes/statistics & numerical data , Social Behavior Disorders/epidemiology , Aged , Forecasting , Germany , Humans , Population Growth
16.
Z Gerontol Geriatr ; 31(6): 417-25, 1998 Dec.
Article in German | MEDLINE | ID: mdl-9916275

ABSTRACT

Providing adequate care of the aged, geriatric caregivers take a key position for the transfer of gerontological knowledge into practice. However, little attention has been focussed on the work conditions and staff distress by gerontologists. The purpose of this paper is to review studies on occupational stress relating to professional geriatric caregivers. Based on relevant research concepts and paradigms, findings of the international literature are summarized. The review shows that occupational stress is affected by a number of work-related factors from behavior problems of the residents to time pressure and organizational deficits. The stress in turn can cause burnout, mental health problems, somatic complaints, and increased turnover. Social support and control at the workplace are supposed to contribute essentially to stress reduction. There are few empirical studies dealing with occupational stress among geriatric caregivers in Germany. Strengths and weaknesses of the studies will be analyzed and suggestions offered for future research in this area. Extending research is needed particularly on the work conditions in the increasing field of geriatric outpatient community services. Inspite of its theoretical and methodological shortcomings, the findings highlight the need for strategies to prevent physical and mental health problems, burnout, and job turnover. It is a challenge for gerontological research to obtain more knowledge on the work-related factors leading to stress as well as to establish effective intervention strategies to reduce its long-term consequences.


Subject(s)
Geriatric Nursing , Job Satisfaction , Occupational Diseases/psychology , Stress, Psychological/complications , Workload , Aged , Humans
17.
Biochem Biophys Res Commun ; 232(3): 742-8, 1997 Mar 27.
Article in English | MEDLINE | ID: mdl-9126347

ABSTRACT

In the present study, the possible involvement of homeobox-containing genes in colorectal cancer (CRC) development was investigated. Using a stepwise screening approach and RT-PCR, we have demonstrated that the human HOXB6, B8, C8 and C9 are overexpressed at various stages of CRC. In contrast, all CRC cases exhibited a marked decrease in the homeodomain-containing Cdx1 gene expression. Recent data which suggest a regulatory link between HOXB8 and several tumor suppressor genes, such as DCC, APC, and TGF beta, sustain a possible implication of homeobox genes in colon carcinogenesis. Moreover, our data showing a decrease in Cdx1 expression are consistent with the notion that genes functioning in the establishment and maintenance of the intestinal epithelium might, upon deregulation, disturb the normal control of cellular proliferation, differentiation, and death, thus leading to cancer development.


Subject(s)
Colorectal Neoplasms/etiology , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Genes, Homeobox , Base Sequence , DNA Primers/genetics , DNA, Complementary/genetics , Genes, Tumor Suppressor , Homeodomain Proteins/genetics , Humans , Polymerase Chain Reaction
18.
Br J Cancer ; 74(3): 394-9, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8695354

ABSTRACT

The arotinoid Ro 40-8757 was previously shown to inhibit the growth of a variety of human cancer cell lines derived from breast, lung and uterus. In view of the high incidence of human digestive cancers, and the slow progress in the development of new therapy, we examined in this paper several combinations between the new arotinoid Ro 40-8757, 5-fluorouracil (5FU) and interferon alpha-2a on the growth of nine human cancer cell lines derived from the gastrointestinal and pancreatic system. Half-maximal inhibition of cell proliferation by Ro 40-8757 was observed at concentrations ranging between 0.18 and 0.57 microM, and increased up to 4.7 microM in retinoid-resistant CAPAN 620 pancreatic cells. All-trans-retinoic acid was 70 times less potent. The sensitivity of HT29-5FU-resistant colonic cells was similar to that observed in the parental cells, suggesting an action independent of pyrimidine metabolism. Ro 40-8757 did not induce any differentiation on HT29 cells, as suggested by ultrastructural analysis. The arotinoid did not interact with receptor signal transduction pathways under the control of serum components, such as growth factors as half-maximal inhibiton of growth was similar in HT29-S-B6 cells cultured in the absence or presence of serum. Cell cycle analysis showed that Ro 40-8757 was not acting at a phase-specific transition in HT29 cells and, accordingly, did not induce overexpression of the protein kinase C (PKC)alpha isoform, or conversion of hyperphosphorylated p105 Rb into hypophosphorylated forms. However, the arotinoid induced significant accumulation of the dephosphorylated, active form of the tumour-suppressor protein. Combinations of Ro 40-8757 with 5FU and interferon alpha 2a resulted in an additive but not synergistic antiproliferative action in HT29 cells. Our data support the interest in Ro 40-8757 as a potent anti-cancer drug, especially in combination therapy with 5FU and interferon, in gastrointestinal and pancreatic cancers, where new active therapeutic modalities are urgently needed.


Subject(s)
Antineoplastic Agents/pharmacology , Fluorouracil/pharmacology , Interferon-alpha/pharmacology , Morpholines/pharmacology , Retinoids/pharmacology , Cell Cycle/drug effects , Cell Division/drug effects , Drug Synergism , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/pathology , Humans , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Protein Kinase C/genetics , Tumor Cells, Cultured
19.
Gesundheitswesen ; 58(4): 201-6, 1996 Apr.
Article in German | MEDLINE | ID: mdl-8688570

ABSTRACT

Cross-sectional studies conducted in 1988 and 1992 using identical assessment methods also determined the prevalence of psychotropic drug consumption by the residents of homes for the elderly in the city of Mannheim. Another purpose of the studies was to find out the extent of a possible interrelation between treatment with psychotropics on the one hand and sociodemographic sociodemographic characteristics and behaviour problems of the residents on the other. In addition, in all consecutive new admissions to the homes not only the prevalence of consumption of psychotropics was investigated, but also the question to what extent the use of psychotropic drugs increases the mortality rate. In a total of 12 Mannheim old-age homes each in 1988 (n = 542) and 1992 (n = 497) all the residents older than 65 years of age were investigated. Between 1986 and 1988 all consecutive admissions (n = 239) to Mannheim old-age homes were interviewed and the mortality risk determined in a subsequent investigation in 1992. Taking a period of four weeks as reference period, 42.1% of the residents were treated during that period with psychotropics in 1988, of which 13.3% received neuroleptics, 11.7% hypnotics, 8.9% antidepressants and 13.0% tranquilizers. There were considerable variations between the individual homes in respect of the intake of psychotropics (minimum 18.2%, maximum 58.3%). In 1992 the prevalence of the use of psychotropics rose to 47.6%, the increase being mainly due to neuroleptics (23.8%) and, to a lesser extent, to antidepressants (12.9%). Compared with 1988 there was a slight decrease in the consumption of tranquilizers (10.9%) and hypnotics (10.7%). In 1988 there was no statistically significant connection between intake of psychotropics and gender, age, frequency of visits by relatives/friends, duration of residence and behaviour problems (aggression, suspiciousness, wandering, depression, dementia) of the residents. This result was also confirmed for 1992, albeit with two exceptions: a significantly higher consumption of psychotropic drugs by home residents characterised by the "behaviour problems wandering" and "depression". Examination of the consecutively newly admitted inmates revealed that psychotropic drug consumption was already relatively high (38.0%) at the time of admission. The mortality risk, determined after having checked on possibly confounding variables, was not significantly enhanced in residents who had already been treated with psychotropics at the time of admission (odds ratio: 0.52; Cl: 0.25-1.08). Compared with elderly persons in private households the consumption of psychotropics is markedly higher in old-age homes. However, the intake is not due to institutionalisation, but had already been high at the time of admission. Prospective studies of the course with relatively short follow-up intervals would be necessary for a differentiated examination of the determinants and effects of high psychotropics consumption and to establish a sound foundation for an appropriate prescription of psychotropics for home residents.


Subject(s)
Dementia/epidemiology , Homes for the Aged/statistics & numerical data , Psychotropic Drugs/therapeutic use , Aged , Cause of Death , Cross-Sectional Studies , Dementia/drug therapy , Dementia/mortality , Drug Utilization , Female , Germany/epidemiology , Humans , Male , Psychotropic Drugs/adverse effects , Risk Factors , Survival Rate
20.
Oncogene ; 12(1): 153-8, 1996 Jan 04.
Article in English | MEDLINE | ID: mdl-8552386

ABSTRACT

Colorectal cancer (CRC) is one of the most frequent cancers in humans. It develops via a multistage process involving alterations of both protooncogenes and tumor suppressor genes. In the present report we determined the level of expression of several Wnt genes in CRC by RT-PCR and direct sequencing. While Wnt-1 was not detectably expressed in any colonic tissues, Wnt-5a gene was efficiently expressed both in nontumorous as well as in colonic tumor tissues. In contrast, the Wnt-2 gene, which was expressed at low levels in normal colon, exhibited overexpression in all tumor tissue samples at the different Dukes' stages of CRC progression, including premalignant polyps and liver metastases. Overexpression of the Wnt-2 gene occurred also in other digestive neoplasms such as gastric and esophageal carcinomas, as well as in diverticulitis associated with stenosis or pseudo-tumor.


Subject(s)
Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins/genetics , Proto-Oncogenes , Base Sequence , Humans , Molecular Sequence Data , Polymerase Chain Reaction , Wnt2 Protein
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