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1.
J Adv Nurs ; 36(1): 69-77, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11555051

ABSTRACT

AIM OF THE STUDY: Research has shown that caring for a dying child is among the hardest and more demanding tasks in nursing, because the staff are forced to manage their heavy work with inadequate skills and experience. This article deals with the findings of a recent study, the purpose of which was to analyse the mother's grief and coping with grief following the death of a child under the age of 7 years. DESIGN: Data were collected from mothers using a survey (n=91) and an interview (n=50). As the topic was very sensitive ethically and emotionally, survey data were collected first and the mothers were asked to give their consent to taking part in an interview. The study employed both quantitative and qualitative methods. The data were analysed using statistical methods and content analysis. However, only the qualitative part of the study is presented in this article. FINDINGS: The findings show that nursing staff had skills to support grieving mothers, but that there were many feelings and experiences of grief that remained unidentified by staff. The staff's ability to meet the mothers' individual needs while the child was in hospital and after the child's death was inadequate. The information received from staff was perceived to be insufficient or offensive to mothers. CONCLUSIONS: The development of basic and further education and of various support measures would enable the staff to better cope with their work. Focusing on interactive skills and meeting the patient's individual needs using reflective practice would improve the quality of care. Communication and collaboration between different occupational groups should be promoted, because mothers were dissatisfied with dissemination of information, and ambiguous responsibilities between different occupational groups hampered the acquisition of information.


Subject(s)
Adaptation, Psychological , Caregivers/psychology , Grief , Mothers/psychology , Nurse-Patient Relations , Adult , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Interviews as Topic , Middle Aged , Terminal Care
2.
Heart Lung ; 30(4): 302-11, 2001.
Article in English | MEDLINE | ID: mdl-11449217

ABSTRACT

OBJECTIVE: The purpose of this study was to identify the prevalence of fear and anxiety in patients awaiting coronary artery bypass grafting and the factors associated with high fear and high anxiety. DESIGN: The survey included 240 patients placed on the waiting list for coronary artery bypass grafting at one hospital. SUBJECTS: Two hundred and seven patients completed the questionnaire. INSTRUMENTS: The Bypass Grafting Fear Scale, the State-Trait Anxiety Inventory, and the Hospital Anxiety and Depression Scale were used. RESULTS: Half of the patients experienced low fear and anxiety. Twenty-five percent had high fear, but only 5% had high anxiety. Patients who felt high fear were mainly women, had no vocational education, were on sick leave, were depressed, had a tendency towards anxiety, and had a short wait for operation. Patients who displayed medium or high anxiety were mostly under 55 years of age and had depression, but only low or no pain. CONCLUSIONS: The results facilitate better identification of predictors of high fear and anxiety as well as direct support and information for those patients.


Subject(s)
Anxiety/epidemiology , Anxiety/psychology , Coronary Artery Bypass/psychology , Coronary Artery Bypass/statistics & numerical data , Fear/psychology , Adult , Age Distribution , Aged , Comorbidity , Depression/epidemiology , Depression/psychology , Educational Status , Employment/psychology , Employment/statistics & numerical data , Female , Finland/epidemiology , Humans , Logistic Models , Male , Marital Status/statistics & numerical data , Middle Aged , Pain/epidemiology , Prevalence , Quality of Life/psychology , Sex Distribution , Sick Leave/statistics & numerical data , Surveys and Questionnaires , Waiting Lists
3.
J Adv Nurs ; 33(4): 503-11, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11251738

ABSTRACT

UNLABELLED: AIMS OF THE PROJECT: The main goal of the 'teacher candidates' reflective teaching and learning' project was to integrate theories of reflection in education and nursing practice. This was realised through teacher candidates' practical training in a hospital setting providing them with personal experiences of reflection in different forms and contexts. In this paper one teacher candidate pair's experiences of developing documentation in one operating theatre are described. BACKGROUND: The power of reflection is acknowledged in health care education and, on the other hand, also in nursing practice. Reflection, however, is not spontaneous but it requires active contribution. The key persons in this respect seem to be healthcare teachers. The challenges for today are that, for example, the theoretical background of reflection is multi-fold and that the concept of reflection is popularised in common use. DESIGN OF THE PROJECT: The project (1995-1998) was accomplished in one of the biggest university hospitals in Finland. On the collaborating wards, systematic team supervision was in progress. Teacher candidates planned and implemented in-service-training modules for teams based on educational needs raised during team supervision sessions. FINDINGS: The contribution of the project can be assessed as important to health care teacher education, but also to nursing practice. Practical training in a hospital setting enhanced teacher candidates' ability to work as teachers in a hospital organisation as well as a nursing college/polytechnic by providing them with a new viewpoint. They learned valuable lessons from applying theory, as planning in-service-training required continuous reflective discussion with the nursing staff but also theoretical reflection. Improvements in nursing practice were also promoted as staff educational needs were met. CONCLUSIONS: Shifting the teacher candidates' practical training into a hospital setting and emphasising reflection seemed to promote their professional development towards teacherhood and improve nursing practice.


Subject(s)
Attitude of Health Personnel , Clinical Competence/standards , Education, Nursing, Continuing/organization & administration , Education, Nursing, Graduate/organization & administration , Faculty, Nursing , Inservice Training/organization & administration , Learning , Nursing Faculty Practice/organization & administration , Nursing Staff, Hospital/education , Teaching/methods , Thinking , Adult , Finland , Hospitals, University , Humans , Models, Educational , Models, Nursing , Nursing Education Research , Nursing Evaluation Research , Program Evaluation
4.
J Adv Nurs ; 33(4): 492-502, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11251737

ABSTRACT

AIM(S) OF THE STUDY: This study is part of a larger research project (1995-1998) aiming at quality improvement by means of clinical supervision (CS). The purpose of the study is to ascertain the conceptions of five ward teams having CS of its effects on the quality of care. BACKGROUND: The quality of nursing care has been debated since at least the 1980s. An extensive literature and research reports describe a variety of interventions and methods to improve the quality of care. One of the interventions is CS. However, the amount of empirical research exploring the effects of CS especially on the quality of care is limited. METHOD: Data were collected using group interviews and analysed using the method of phenomenography. FINDINGS: The following categories describing the conceptions related to CS and to the quality of care emerged: knowledge, change and 'I and we as providers of quality'. Conceptions of the effects varied between and within the teams and sometimes contradicted each other. The importance of knowledge was underlined on three of the five wards. The patient's point of view emerged only on one ward. CONCLUSIONS: It can be concluded that CS has effects on the quality of care and it can be considered a quality improving intervention in nursing practice. However, the knowledge of the different conceptions produced in this study also gives proof that team supervision is a challenge for supervisors.


Subject(s)
Attitude of Health Personnel , Clinical Competence/standards , Nursing Care/standards , Nursing Staff, Hospital/psychology , Nursing Staff, Hospital/standards , Nursing, Supervisory/organization & administration , Nursing, Team/organization & administration , Patient Care Team/organization & administration , Quality of Health Care , Total Quality Management/organization & administration , Finland , Focus Groups , Hospitals, University , Humans , Nursing Methodology Research , Nursing Staff, Hospital/education , Surveys and Questionnaires
5.
Int J Nurs Stud ; 38(3): 297-303, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11245866

ABSTRACT

The purpose of this study was to compare family dynamics in child maltreating families (n=42) with that in ordinary families with children (n=77), and to ascertain risk factors of child maltreatment within the family. Child maltreatment was defined as physical, psychological or sexual abuse or neglect of a child by a parent. Data were collected using questionnaires (Family Dynamics Measure 2, FMD 2) (N=119) basing on Barnhill's conceptual framework of healthy family systems and analysed by forming sum variables and logistic regression. The study results indicate that family functioning in child maltreating families is lower on all dimensions of family dynamics (individuation, mutuality, flexibility, stability, communication and roles) than that in ordinary families with children. Furthermore, it seems that specific risk factors, detected with logistic regression analysis, are related to whether child maltreatment occurs in the family or not. These include the parent's low educational background, many children in the family, unemployment of a parent, low individuation of the family members, and poor stability and security within the family. The results of this study provide guidelines for detecting and preventing child maltreatment as well as for recognising its existence, although no generalizations can be made due to the small sample size and complexity of the phenomenon under study.


Subject(s)
Child Abuse/psychology , Family Nursing/methods , Family/psychology , Adult , Case-Control Studies , Child , Child Abuse/prevention & control , Communication , Educational Status , Family Characteristics , Family Nursing/standards , Humans , Knowledge , Logistic Models , Nursing Assessment , Nursing Methodology Research , Practice Guidelines as Topic , Risk Factors , Role , Surveys and Questionnaires , Systems Analysis
6.
Proc Natl Acad Sci U S A ; 98(3): 1024-9, 2001 Jan 30.
Article in English | MEDLINE | ID: mdl-11158588

ABSTRACT

Endostatin, a fragment of collagen XVIII, is a potent antagonist of angiogenesis and inhibitor of tumor growth in mouse models. At present, the mechanism of action of endostatin is unknown. We show here that recombinantly produced human endostatin interacts with alpha(5)- and alpha(v)-integrins on the surface of human endothelial cells. We further demonstrate that the endostatin-integrin interaction is of functional significance in vitro, as we found that immobilized endostatin supports endothelial cell survival and migration in an integrin-dependent manner. Soluble endostatin in turn inhibits integrin-dependent endothelial cell functions, such as cell migration. Taken together, these results implicate integrins as potential targets for endostatin function and support the importance of integrins in endothelial cell biology and angiogenesis.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Antigens, CD/physiology , Collagen/pharmacology , Collagen/physiology , Endothelium, Vascular/physiology , Peptide Fragments/pharmacology , Peptide Fragments/physiology , Animals , Cell Adhesion/drug effects , Cell Movement/drug effects , Cells, Cultured , Collagen/chemistry , Collagen Type XVIII , Edetic Acid/pharmacology , Endostatins , Endothelium, Vascular/cytology , Epidermal Growth Factor/pharmacology , Fibroblast Growth Factor 2/pharmacology , Focal Adhesion Kinase 1 , Focal Adhesion Protein-Tyrosine Kinases , Humans , Integrin alpha5 , Integrin alphaV , Kinetics , Mice , Oligopeptides/pharmacology , Phosphorylation , Protein-Tyrosine Kinases/metabolism , Recombinant Proteins/metabolism , Umbilical Veins
7.
Int J Nurs Stud ; 38(1): 17-24, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11137719

ABSTRACT

The aim of this paper was to describe testing a Finnish version of the assessment of strategies in families (ASF) instrument and its construct validity and reliability in Finnish families. The ASF instrument is based on Friedemann's framework of systemic organization and the version used in this study consists of 25 items, each containing three statements. The instrument was developed to estimate family functioning in reaching the four targets of the framework of systemic organization. It provides sub-scores for the targets, family stability (system maintenance and coherence), family growth (system change and individuation), control (system maintenance and system change) and spirituality (individuation and coherence). Data were collected from patients attending the outpatient clinics of pulmonary and rheumatic diseases (N=196). Questionnaires were given to patients capable of understanding the questions and they returned questionnaires by mail directly to researchers. Construct validity was tested with exploratory factor analysis. Factor analysis was done with 22 items. The four factor solution was best suited. Two items were eliminated because of low factor loadings and crossloading. The total of 20 items were left in the instrument. Crohnbach's alpha was used to measure internal consistency. It was computed for each target separately and the total tool. There were discrepancies in the assignment of process dimensions which were expected because of cultural perceptions. The total instrument had a reliability of 0.85. The result of the analyses was a pretested tool with subscales for stability, growth, control and spirituality that have acceptable reliability and concept validity. Less satisfactory was the small number of items representing individuation. Another weakness is the lack of statistical distinction between system maintenance and coherence. The instrument is also usable in these subscales, but it needs further development and retesting. Items need to be added to express individuation, possibly some others. The new items will be formulated freely, paying attention to culture. However, the tool appears good enough to be used as measurement in various research studies.


Subject(s)
Adaptation, Psychological , Family Health , Family/psychology , Health Status , Nursing Assessment/methods , Adult , Aged , Factor Analysis, Statistical , Female , Finland , Humans , Internal-External Control , Lung Diseases/nursing , Lung Diseases/psychology , Male , Middle Aged , Models, Psychological , Nursing Assessment/standards , Nursing Evaluation Research , Religion and Psychology , Rheumatic Diseases/nursing , Rheumatic Diseases/psychology , Surveys and Questionnaires , Systems Analysis , Translating
8.
J Nurs Manag ; 9(5): 259-68, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11879468

ABSTRACT

AIM: To develop a model of costs and benefits of team supervision and a formula, which are examined more closely by means of an example. BACKGROUND: The popularity of clinical supervision (CS) as one of the methods of supporting health care practitioners' professional development (formative function), coping (restorative function) and quality improvement (normative function) has increased in the 1990s. CS may take the form of one-to-one or group supervision. Team supervision is a special form of group supervision. It means a group that has an interrelated work life outside the group. A host of literature and articles is available on CS. However, the costs and benefits of CS are less examined even though these have given rise to discussion particularly among decision-makers, because the monetary benefit of CS remains unsolved. METHOD: A nominal group technique was used to develop a model of costs and benefits of team supervision and a formula was derived on the basis of the model. The existing statistical data, for example a hospital ward's annual reports, data on sick days and reports on indemnities were utilized in the application of the formula. FINDINGS AND CONCLUSION: Team supervision was efficient in economic terms on the example ward. The model and the formula constitute a first attempt to ascertain the net present benefit of team supervision. Both the model and the formula need to be further tested, specified and refined.


Subject(s)
Hospital Units/organization & administration , Models, Nursing , Nursing Administration Research , Nursing, Supervisory/economics , Nursing, Team/economics , Cost-Benefit Analysis , Finland , Hospital Costs , Hospital Units/economics , Hospitals, University/organization & administration , Humans , Models, Organizational , Organizational Case Studies
9.
J Nurs Manag ; 9(5): 287-94, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11879472

ABSTRACT

AIM: The study aimed at ascertaining the objectives, development strategies and problems of ward sisters in developing nursing. BACKGROUND: More knowledge is needed of first-line management in order to be able to develop organizations and ward sisters' professional training. METHODS: Data collection was by a questionnaire completed by 37 ward sisters in two Finnish hospitals. Thirty-six ward sisters responded to the open-ended questions and their answers were analysed using content analysis. FINDINGS: As for their objectives, ward sisters emphasized a functioning working community and good care. Good care was based on a variety of theoretical ideas, on the quality and economy of care. The means by which these objectives could be achieved were process thinking, reflection on action, leadership and the development of the working community. The leadership strategies mentioned were profit management and participatory leadership. In developing the working community, ward sisters relied on collaboration, good climate and training. Ward sisters' problems with developing nursing care were related to resources, work organization and the working community. CONCLUSIONS: Besides expertise in nursing, ward sisters are required to have skills in leading and developing the working community, collaboration and especially the ward's climate.


Subject(s)
Nursing Staff, Hospital/organization & administration , Nursing, Supervisory , Adult , Female , Humans , Leadership , Middle Aged , Nursing Administration Research , Organizational Objectives , United Kingdom
10.
J Clin Nurs ; 10(4): 538-49, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11822502

ABSTRACT

The study aimed at ascertaining the gender differences and fears among patients awaiting coronary artery bypass grafting. Data were collected using a mailed questionnaire from patients (n=207) scheduled for coronary artery bypass grafting at one hospital. Intensity of fear was measured on a 10-point scale including 12 objects of fear. The results showed that demographic data, lifestyle and functional capacity differed between the sexes. Patients' fears differed with respect to their objects and intensity, with women reporting more intense fears. Men also had fears, but the objects of fear differed from those in women. Apart from gender, the intensity of fear was associated with physical exercise, emotional problems and depression. Nursing interventions could be developed to meet the different needs for information and support, especially among women but also among men, to relieve their fears during the wait for coronary artery bypass grafting.


Subject(s)
Attitude to Health , Coronary Artery Bypass/psychology , Fear , Preoperative Care/psychology , Sex Factors , Waiting Lists , Activities of Daily Living , Adult , Aged , Coronary Artery Bypass/nursing , Depression/psychology , Exercise/psychology , Female , Finland , Humans , Life Style , Male , Mental Health , Middle Aged , Needs Assessment , Nursing Methodology Research , Patient Education as Topic , Preoperative Care/nursing , Surveys and Questionnaires
11.
Scand J Caring Sci ; 15(2): 142-50, 2001.
Article in English | MEDLINE | ID: mdl-12078627

ABSTRACT

The purpose of this study was to generate knowledge of the interaction between an adult patient's family members and nursing staff from the staff's perspective. Data were collected from nursing staff (n = 155) working on the wards and out-patient departments for pulmonary, rheumatic, neurological and gastroenterological diseases at a university hospital by using a new questionnaire based on earlier research and the literature. The questions explored the staff's views of interaction with the adult patient's family members. In this study, interaction is seen as an umbrella concept which encompasses giving information to relatives, discussion, contacts between staff and significant others and working together. The instrument included questions about personal and telephone discussions, the provision of written instructions and factors facilitating and complicating interaction. The response rate was 55%. The data were analysed using SPSS software and examined using frequency and percentage distributions and cross-tabulation. The open-ended questions were analysed using qualitative content analysis by reducing, grouping and abstracting the data inductively. Discussions with relatives while they visited the patient in hospital were the commonest form of interaction. The majority of respondents perceived the interaction with the patient and knowing his or her family members as important. Less than one-fourth of the respondents started discussion with family members, while the majority expected family members to initiate interaction. The majority of respondents perceived the patient's presence in discussion as important, but sometimes they thought it was necessary to discuss with family members without the patient. The staff discussed with family members mainly in the ward office or in patient rooms, which were, however, not perceived as peaceful. Discussions primarily pertained to the patient's condition, discharge from hospital and planning of continued treatment. The majority of respondents reported that the opportunity for discussion offered by staff, the patient's positive attitude towards discussion with the family and family members' own interest facilitated interaction. The staff's haste and shift-work, family members' shyness of approaching the staff and the absence of a peaceful place for discussion serve to complicate interaction. Family members are primarily seen as informants and recipients of information. The staff's ability to recognize the importance of family members to successful patient care is relatively adequate. However, insufficient attention is paid to family members and their need for support.


Subject(s)
Nurse-Patient Relations , Nursing Staff, Hospital , Professional-Family Relations , Adult , Ethics , Female , Humans , Male , Middle Aged
12.
Cancer Nurs ; 23(6): 483-91, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11128128

ABSTRACT

This study describes the impact of a supportive telephone call on grief 4 months after the death of a family member. The study design involved a quasi-experimental intervention group (n = 70) and a control group (n = 155). The intervention was a supportive telephone call after the death of a family member. Grief reactions were measured with the Hogan Grief Reactions Checklist. Results were completed by content analysis of family members' experiences of the intervention. Chi-square and t tests were used to compare the associations with demographic data, and logistic regression analysis was used to compare the responses. The results pointed to differences in despair and personal growth between the groups. The participants experienced the supportive telephone call positively for the most part. Negative experiences were associated with promises to call in which the call never reached the participant. Grieving family members' positive experiences of the call indicate that there is a need for individual support after the death, given by nurses of the wards in which the deceased received care.


Subject(s)
Death , Family , Grief , Oncology Nursing , Telephone , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Humans , Male , Middle Aged , Oncology Nursing/methods , Social Support
13.
Int J Nurs Pract ; 6(4): 174-82, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11261046

ABSTRACT

Nursing takes place in a working community and the working community influences the quality of nursing. The purpose of this study was to find out the effects of nurses' individual characteristics, working conditions, and the ward sisters' management skills on working climate and team spirit. Thirty-seven wards of two Finnish hospitals took part in the study, and 717 nurses answered the questionnaire. Statistical analyses indicate that the ward sister's management skill is the best predictor of the climate and team spirit of the wards as perceived by nurses. The nurses' age, education, and working experience have no direct effect on the working community. Nurses who work by the day, who have plenty of further education and permanent employment, are most likely to be dissatisfied with the climate. According to the results, it is important that the ward sister provides sufficient opportunities for professional development, especially for those who are highly motivated to advance their careers. The ward sister can influence the ward's team spirit also by furthering operational preconditions of the ward.


Subject(s)
Attitude of Health Personnel , Interprofessional Relations , Morale , Nursing Care/standards , Nursing Staff, Hospital/organization & administration , Nursing Staff, Hospital/psychology , Nursing, Supervisory/organization & administration , Quality of Health Care , Workplace/organization & administration , Adult , Finland , Humans , Middle Aged , Nursing Methodology Research , Nursing Staff, Hospital/education , Organizational Culture , Surveys and Questionnaires
14.
Atherosclerosis ; 138(2): 367-74, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9690921

ABSTRACT

Hypertriglyceridemia is a heterogeneous lipid disorder often running in families. Variation in the apolipoprotein B (apo B) gene has been associated with serum triglyceride levels. Recently, a role of the amino-terminal end of apo B in binding with lipoprotein lipase (LPL) has been suggested. We screened the 5' end of the apo B gene in 76 Finnish severely hypertriglyceridemic (> 6 mmol/l) patients, using a single-strand conformation polymorphism (SSCP) screening method. We detected a previously unreported polymorphic C2316-->A change, causing a Val703-->Ile substitution. The minor 703 Ile allele frequency was 0.04 in hypercholesterolemic and normolipidemic population samples. This allele was associated with lower serum triglyceride levels in a normolipidemic population sample. Analysis of two previously reported polymorphisms also located in the amino-terminal domain of apo B (Thr71-->Ile and Val591-->Ala) revealed elevating effects on serum apo B concentrations in hypertriglyceridemic individuals. The 591 Ala allele was associated with elevated apo B (P=0.011), and individuals with both minor alleles (apo B 591 Ala + and apo B 71 Ile +) had higher apo B levels compared to subjects homozygous for both common alleles (P=0.004). Although no DNA sequence change seemed to be the cause of hypertriglyceridemia in our patients, genetic variation in the 5' end of the apo B gene may contribute to changes in serum apo B levels in hypertriglyceridemic patients.


Subject(s)
Apolipoproteins B/genetics , Hyperlipidemias/genetics , Polymorphism, Genetic , Adult , Codon , Female , Genetic Variation , Humans , Male , Middle Aged
15.
Diabetes Care ; 21(4): 477-81, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9571327

ABSTRACT

OBJECTIVE: To compare the lipid-lowering efficacies of simvastatin and gemfibrozil in NIDDM patients with combined (mixed) hyperlipidemia (CHL) or isolated hypercholesterolemia (IHC). RESEARCH DESIGN AND METHODS: Patients with primary dyslipidemia and NIDDM were recruited for this double-blind, double-dummy comparison study from 10 Finnish centers. After a 4-week placebo run-in period, they were randomly assigned to simvastatin or gemfibrozil. The simvastatin group (n = 47) received 10 mg once nightly for 8 weeks, 20 mg for the next 8 weeks, and 40 mg for the third 8-week period. The gemfibrozil group (n = 49) received 600 mg twice daily throughout the 24 weeks. The lipid-lowering efficacies of both drugs were compared in all patients as well as separately in patients with CHL and IHC. RESULTS: In all patients, simvastatin reduced LDL and total cholesterol and the LDL-to-HDL cholesterol ratio more effectively, whereas gemfibrozil was more effective in elevating HDL cholesterol and decreasing triglyceride levels. The drug effects differed according to lipid phenotype at baseline. Simvastatin decreased LDL cholesterol levels by 30-40% in both phenotypes. Gemfibrozil caused a 15% reduction in LDL cholesterol in IHC but no change in CHL patients. Simvastatin produced 15-30% reductions in triglyceride levels in CHL but no change in IHC patients. Gemfibrozil caused reductions in triglycerides in CHL (50% and more) and in IHC (40%) patients, with 12-18% increases in HDL cholesterol in these groups. CONCLUSIONS: Simvastatin is useful in both CHL and IHC patients, whereas gemfibrozil can be used in patients with high triglyceride and low or normal LDL cholesterol levels.


Subject(s)
Anticholesteremic Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Gemfibrozil/therapeutic use , Hypercholesterolemia/drug therapy , Hyperlipidemias/drug therapy , Hypolipidemic Agents/therapeutic use , Simvastatin/therapeutic use , Blood Glucose/drug effects , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Diabetes Mellitus, Type 2/blood , Double-Blind Method , Female , Finland , Glycated Hemoglobin/analysis , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Hyperlipidemias/blood , Hyperlipidemias/complications , Male , Middle Aged , Time Factors , Triglycerides/blood
16.
Atherosclerosis ; 128(2): 191-9, 1997 Feb 10.
Article in English | MEDLINE | ID: mdl-9050776

ABSTRACT

Hypercholesterolemia clustering in families not explained by either low density lipoprotein (LDL)-receptor mutations producing familial hypercholesterolemia (FH), or the apolipoprotein B (apo B) Arg3500-->Gln mutation with familial defective apo B (FDB), is common in the Finnish population. In search of previously unknown apo B mutations, we screened exons 26 to 29 of the apo B gene in 68 Finnish severely hypercholesterolemic (> or = 8 mmol/l) non-FH, non-FDB patients, using a single-strand conformation polymorphism analysis based screening method. Four rare and two polymorphic previously unreported DNA variations were detected. The rare variants were a three-nucleotide deletion, with the deletion of Asp2186, an A11961-->G change leading to a Thr3918-->Ala change, a T12922-->G change causing a Val4238-->Ala substitution, and a neutral T12935-->C change leading to a new RsaI cutting site. The polymorphic G12937-->C and G13569-->A changes leading to Arg4243-->Thr and Ala4454-->Thr substitutions, respectively, had minor allele frequencies of 0.03 and 0.02. None of these variants seemed to explain the hyperlipidemia in these patients. A major Finnish mutation causing severe hypercholesterolemia is unlikely to exist in the 3' two-thirds of the coding area of the apo B gene.


Subject(s)
Apolipoproteins B/genetics , Genetic Code , Genetic Testing , Genetic Variation , Hypercholesterolemia/genetics , Base Sequence , Exons , Finland , Gene Frequency , Haplotypes , Humans , Lipids/blood , Pedigree , Polymorphism, Genetic , Polymorphism, Single-Stranded Conformational
17.
Clin Chim Acta ; 256(1): 27-36, 1996 Dec 09.
Article in English | MEDLINE | ID: mdl-8960785

ABSTRACT

The U937 myelomonocyte proliferation assay can be used to detect patients with familial defective apolipoprotein B-100 (FDB). Previous studies have employed electronic cell counting to assess cell proliferation. We simplified the assay using 3H-thymidine incorporation DNA analysis to measure cell growth. We tested the modified method by analyzing the effects of different concentrations of native low density lipoproteins (LDL), methylated LDL, as well as LDLs obtained from patients with FDB on cell growth. Methylation of LDL to various degrees reduced cell proliferation correspondingly, and LDLs obtained from FDB patients decreased cell growth confirming that the modified method was able to detect binding defective species of LDL. We applied this method to analyze three novel apoB polymorphisms recently characterized in this laboratory (apoB His1896-->Arg, apoB Asn1887-->Ser, apoB Ala4454-->Thr), which did not significantly alter U937 cell proliferation. Our results show that this simplified assay can be used for screening for LDL variants with defective binding.


Subject(s)
Apolipoproteins B/genetics , Apolipoproteins B/pharmacology , Biochemistry/methods , Lipoproteins, LDL/metabolism , Lymphoma, Large B-Cell, Diffuse/metabolism , Mutation/genetics , Alleles , Apolipoproteins B/analysis , Female , Humans , Lipoproteins, LDL/drug effects , Male , Protein Binding/drug effects , Protein Binding/physiology , Tumor Cells, Cultured
18.
Arterioscler Thromb Vasc Biol ; 15(9): 1287-93, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7670940

ABSTRACT

In previous studies, apoB polymorphisms have been shown to modify serum lipid responses to changes in dietary fat intake. The functionally important apoB DNA change or changes underlying these effects have, however, remained unknown. Using a single-strand conformation polymorphism analysis-based screening method, we identified two previously unreported apoB polymorphisms located close to each other in the 5' region of apoB gene exon 26. This DNA segment corresponds to the binding site of monoclonal anti-apoB antibody D7.2. The two A-->G changes at apoB cDNA nucleotides 5869 and 5896 produced an Asn-->Ser change at amino acid 1887 and a His-->Arg change at amino acid 1896. In the Finnish population, allele frequencies of the rare alleles of the apoB 1887 (Asn-->Ser) and apoB 1896 (His-->Arg) polymorphisms were .02 and .11, respectively. Both polymorphisms were shown to have an independent effect on the binding affinity of LDL with monoclonal antibody D7.2. The effect of these polymorphisms on serum lipid levels and responses to changes in dietary fat intake in 102 healthy free-living subjects was assessed. The apoB 1896 Arg allele was associated with a higher serum LDL cholesterol level during a low-fat, low-cholesterol diet in men.


Subject(s)
Apolipoproteins B/genetics , Dietary Fats/administration & dosage , Lipids/blood , Polymorphism, Single-Stranded Conformational , Alleles , Asparagine , Base Sequence , Female , Finland , Gene Frequency , Genetic Variation , Genotype , Humans , Male , Molecular Sequence Data , Pedigree , Polymerase Chain Reaction , Serine
19.
Hum Mutat ; 4(3): 217-23, 1994.
Article in English | MEDLINE | ID: mdl-7833952

ABSTRACT

To date, the only known apolipoprotein B (apo B) mutation causing hypercholesterolemia is the apo B 3500 Arg-->Gln or the familial defective apo B (FDB) mutation. This mutation has not been detected in the Finnish population. We have set up a systematic single-strand conformation polymorphism (SSCP) analysis-based screening method to search for other mutations in the exon 26 of the apo B gene in 21 Finnish hypercholesterolemic probands. The 7572-bp exon 26 covers half of the coding region of the gene including the DNA sequence coding for the putative low-density lipoprotein (LDL) receptor binding site on the apo B protein. Exon 26 was amplified as six 1190- to 1435-bp fragments, each of which was further split into three smaller 213- to 579-bp segments by restriction enzymes. These digestion products were run on nondenaturing polyacrylamide gels using at least three different electrophoretic conditions and autoradiographed. All previously known genetic variants in the exon 26 were detected by the SSCP method. A C-->T change at nucleotide 7064, in complete association with the XbaI site, was characterized by direct sequencing. This variant did not affect the amino acid sequence of the apo B protein. The SSCP-based procedure appears suitable for systematic screening for DNA sequence changes in large coding regions.


Subject(s)
Apolipoproteins B/genetics , Hyperlipoproteinemia Type II/genetics , Mutation , Polymorphism, Genetic , Base Sequence , DNA Mutational Analysis , DNA Primers/genetics , Exons , Female , Finland , Genetic Variation , Humans , Male , Molecular Sequence Data , Point Mutation
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