ABSTRACT
BACKGROUND: The results from clinical studies with statins have directed attention to the benefits of risk factor intervention in atherosclerotic disease, and achievement of treatment goals for blood lipids. MATERIAL AND METHODS: In 1999, a total of 3,935 patients treated with a statin were screened in 412 general practices in Norway for their blood lipids, in order to evaluate the achievement of the new European treatment guidelines (total cholesterol < 5 mmol/l and LDL cholesterol < 3 mmol/l). Inclusion criterion was ongoing medication with a statin, independent of indication. Consecutive patients were interviewed and examined when they attended their regular check-ups. The mean age of the patients was 63 years; 42% of them were women. Two-thirds of the patients were in secondary prevention. RESULTS: Before treatment, the mean level of total cholesterol was in primary prevention 8.8 mmol/l, in secondary prevention and in diabetes 7.5 mmol/l. In the total material, 36% of the patients achieved the treatment goal of total cholesterol and LDL cholesterol. Significantly more patients in secondary prevention than in primary prevention achieved the treatment goal (44% versus 17%), more patients with than without diabetes achieved it (45% versus 34%), and more men than women (42% versus 27%). These differences were mainly due to differences in base levels of total cholesterol and LDL cholesterol. To assess the statin doses, the average dose of each type of statin was converted to a simvastatin dose. The average dose in this manner was found to be 23.8 mg, with small differences between the subgroups. INTERPRETATION: The doctors did not uptitrate the statin doses according to the lipid levels and in line with the evidence from the clinical trials. General practitioners in Norway should intensify their use of lipid lowering therapy.
Subject(s)
Anticholesteremic Agents/administration & dosage , Arteriosclerosis/prevention & control , Cholesterol/blood , Adult , Aged , Arteriosclerosis/blood , Arteriosclerosis/etiology , Arteriosclerosis/genetics , Cholesterol, LDL/blood , Female , Humans , Male , Middle Aged , Primary Prevention , Risk Factors , Triglycerides/bloodABSTRACT
Ataxia-telangiectasia (AT) is a rare autosomal recessive disease with a complex phenotype involving cerebellar degeneration, immunodeficiency, cancer risk and radiosensitivity. Our aim has been to identify Swedish AT patients in order to study the possible "Swedish phenotype" of the disease. In the 19 patients identified in Sweden we found a phenotype fairly similar to what has been described internationally, with the exception of some differences including lower cancer incidence in patients and their relatives and somewhat more pronounced immunodeficiency and concomitant susceptibility to infections.
Subject(s)
Ataxia Telangiectasia/genetics , Adolescent , Adult , Ataxia Telangiectasia/diagnosis , Ataxia Telangiectasia/epidemiology , Ataxia Telangiectasia/immunology , Child , Child, Preschool , Chromosomes, Human, Pair 11 , Disease Susceptibility , Female , Genetic Predisposition to Disease , Humans , Infant , Infant, Newborn , Male , Mutation , Phenotype , Risk Factors , Sweden/epidemiologyABSTRACT
Statin drug treatment has still not achieved complete acceptance, and titration to recommended target goals is still not used by physicians in Norway.
Subject(s)
Anticholesteremic Agents/therapeutic use , Arteriosclerosis/prevention & control , Family Practice , Lipids/blood , Pravastatin/therapeutic use , Simvastatin/therapeutic use , Adult , Aged , Aged, 80 and over , Arteriosclerosis/blood , Arteriosclerosis/epidemiology , Atorvastatin , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cross-Sectional Studies , Family Practice/methods , Family Practice/statistics & numerical data , Fatty Acids, Monounsaturated/therapeutic use , Female , Fluvastatin , Heptanoic Acids/therapeutic use , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Indoles/therapeutic use , Male , Middle Aged , Norway/epidemiology , Pyridines/therapeutic use , Pyrroles/therapeutic use , Retrospective Studies , Surveys and QuestionnairesABSTRACT
Tumor cells and their surrounding microenvironment produce a variety of factors that promote tumor growth and metastasis. We recently identified a nuclear factor, termed com1, that is up-regulated in human breast carcinoma cells on formation of experimental metastatic tumors and is assumed to act as a growth-promoting factor in breast cancer. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is a potent inhibitor of growth in breast cancer both in vitro and in vivo. We compared the growth-regulatory mechanisms of nontumorigenic and estrogen-dependent MCF-7 cells with those of the tumorigenic and tamoxifen-resistant subline MCF7/ LCC2 in the presence of 1,25(OH)2D3. Proliferation of MCF7/LCC2 cells, which revealed constitutive com1 expression, was inhibited by 1,25(OH)2D3 (10(-7) M). This was strongly associated with cell cycle arrest in G1 phase, consistent with accumulation of the hypophosphorylated form of the retinoblastoma protein as well as the induction of the cyclin-dependent kinase inhibitor p21. These cell cycle events were preceded by a transient up-regulation (5-8-fold) of com1 mRNA. Furthermore, clonal growth of the MCF7/LCC2 cells was also inhibited by 1,25(OH)2D3 (10(-7) M), and when the com1-negative MCF-7 cells were stably transfected with com1, the resulting MCF7/com1 cells showed a significant decrease in colony formation. These results seem to indicate that rather than promoting growth, com1 may participate in the regulatory pathway involved in cellular growth inhibition when recruited by inhibitory signals.
Subject(s)
Breast Neoplasms/metabolism , Calcitriol/pharmacology , DNA-Binding Proteins , Gene Expression Regulation, Neoplastic/drug effects , Neoplasm Proteins/biosynthesis , Neoplasms, Hormone-Dependent/metabolism , Basic Helix-Loop-Helix Transcription Factors , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cell Cycle/drug effects , Cell Division/drug effects , Cell Division/physiology , Clone Cells/drug effects , Clone Cells/pathology , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/biosynthesis , Cyclins/genetics , Dexamethasone/pharmacology , Estradiol/pharmacology , Estrogens/physiology , Humans , Neoplasm Proteins/genetics , Neoplasm Proteins/physiology , Neoplasms, Hormone-Dependent/genetics , Neoplasms, Hormone-Dependent/pathology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Tretinoin/pharmacology , Tumor Cells, Cultured , Up-Regulation/drug effectsABSTRACT
In human immunodeficiency virus type 1 (HIV-1) infection, functional activities of T lymphocytes are impaired. Analogous to tumor-infiltrating T lymphocytes from cancer patients, in whom poor proliferative responses are associated with fewer zeta molecules, this study compared expression of CD3zeta molecules by T lymphocytes from HIV-infected persons and healthy controls. Flow cytometry and immunoblotting revealed significantly diminished zeta expression by CD3, CD4, and CD8 T lymphocytes from AIDS patients but not from persons without AIDS. zeta-mRNA levels were also decreased in cells from AIDS patients. CD3zeta expression correlated significantly with CD4 cell counts and HIV-1 RNA levels; impaired expression of CD3zeta molecules appeared to be reversible upon virus load reduction following highly active antiretroviral treatment (HAART). Thus, reduced expression of CD3zeta molecules by T lymphocytes from HIV-infected persons correlates with disease status. Investigations into CD3zeta expression by subpopulations of peripheral T lymphocytes and by T lymphocytes in lymphoid tissues will contribute to the understanding of immune reconstitution of HIV-infected patients following HAART.