The Troms? heart study: coffee consumption and serum lipid concentrations in men with hypercholesterolaemia: an randomised intervention study

In a 10 week trial to assess the effects of coffee consumption and coffee brewing methods on serum cholesterol concentrations 33 men with hypercholesterolaemia were randomly assigned to: continue with their usual coffee intake; stop drinking coffee altogether; or stop drinking coffee for five weeks, thereafter drinking either boiled or filter coffee. Cholesterol concentrations fell significantly in all subjects abstaining for the first five weeks compared with subjects not giving up and continued to fall in those abstaining for 10 weeks. Cholesterol concentrations rose again in subjects returning to boiled coffee but remained the same in those returning to filter coffee. Abstention from heavy coffee drinking is an efficient way of reducing serum cholesterol concentrations in men with hypercholesterolaemia. The extent to which the brewing method affects this relation requires further study.     

Methotrexate and citrovorum factor after histoincompatible allogeneic bone marrow transplants in dogs.

Methotrexate (MTX) followed by citrovorum factor (CVF) rescue was evaluated for its effectiveness in reducing graft-versus-host disease (GVHD) in lethally irradiated dogs transplanted with bone marrow from unrelated histoincompatible donors. Animals were given no immunosuppressive therapy (group A) or a combined regimen of MTX and CVF (group AMC). These two groups were compared with a group of animals transplanted earlier given MTX alone (group AM). Ainmals in the AMC group lived significantly longer than the A group (p less than 0.05). Engraftment rate, hematopoietic recovery and incidence of GVHD were similar in all three groups. Incidence of early deaths was significant in the AM group (p less than 0.05). It is concluded that MTX combined with CVF increases survival and is an effective posttransplantation immunosuppressive regimen with minimal toxicity.     

Indicators of salivary gland inflammation in primary Sjögren's syndrome

The aim of this study was to establish additional indicators in saliva and plasma which are associated with salivary gland inflammation in patients with primary Sjögren's syndrome (SS). ELISA assays were used to determine the concentrations of sICAM-1, sVCAM-1, sIL-2Rz, IgA, IgG, calprotectin and albumin in parotid saliva, whole saliva and plasma samples. Soluble ICAM-1 was present in whole and parotid saliva samples from primary SS patients. Soluble VCAM-1 and sIL-IRx could not be detected in salivary samples from either primary SS or control subjects. IgA, IgG, calprotectin and albumin concentrations were higher in both whole and parotid saliva in the patient group compared with the control group. The results showed increased levels of calprotectin in all saliva samples compared to plasma, suggesting that calprotectin may be locally produced. Increased plasma values of sICAM-1. sVCAM-1, SIL-2Rα, IgA, IgG and calprotectin were detected in primary SS patients when compared to controls. The output/min of IgA. IgG, calprotectin and albumin was decreased in SS patients. Plasma levels of various proteins could offer information concerning glandular and extraglandular inflammatory processes. However, salivary levels of these proteins (particularly sICAM-1) tend to reflect more the local inflammatory activity, providing a convenient and non-invasive tool for diagnosis.     

The Troms? Heart Study: family approach to intervention on CHD. Feasibility of risk factor reduction in high-risk persons--project description

Intervention on high risk persons for CHD has shown varying results depending on the effectiveness of the intervention. Most studies have concentrated on the high-risk person only. The present study focuses on the high-risk family as an entity. 1,373 high-risk men, 30-55 years, were identified on the basis of high total cholesterol and/or low relative HDL (HDL-cholesterol/tot. cholesterol) in the Troms? II screening in 1979/80, and randomly allocated to intervention or control group. The 673 men in the intervention group and their families, were offered advice to reduce their risk during two home visits and later by quarterly newsletters. Follow-up blood samples drawn 1.5 years following the home-visit, show a small reduction in total cholesterol and an increase in the ratio of HDL cholesterol/total cholesterol. Both the intervention and control group were invited to the examination in connection with the Troms? III screening in 1986/87 and are being followed for 10 years on cardiovascular morbidity and mortality.     

Gene rearrangement: a novel mechanism for MDR-1 gene activation.

Drug resistance, a major obstacle to cancer chemotherapy, can be mediated by MDR-1/P-glycoprotein. Deletion of the first 68 residues of MDR-1 in an adriamycin-selected cell line after a 4;7 translocation, t(4q;7q), resulted in a hybrid mRNA containing sequences from both MDR-1 and a novel chromosome 4 gene. Further selection resulted in amplification of a hybrid gene. Expression of the hybrid mRNA was controlled by the chromosome 4 gene, providing a model for overexpression of MDR-1. Additional hybrid mRNAs in other drug-selected cell lines and in patients with refractory leukemia, with MDR-1 juxtaposed 3' to an active gene, establishes random chromosomal rearrangements with overexpression of hybrid MDR-1 mRNAs as a mechanism of acquired drug resistance.     

Medical evaluation of subjects with known body levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin

Forty-one persons with a history of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure and measured adipose tissue TCDD levels were evaluated for potential health effects. No pattern of clinical abnormalities emerged related to TCDD levels.     

Deciphering an outbreak of drug-resistant Mycobacterium tuberculosis

There have been ample warnings that multidrug-resistant (MDR) tuberculosis (TB) will continue to emerge if countries do not strengthen their control of TB. In low-incidence European countries, however, these warnings have been substantiated mainly by outbreaks in association with human immunodeficiency virus (HIV)-positive patients. The aim of this study was to investigate an outbreak of infection with MDR and drug-resistant Mycobacterium tuberculosis that was diagnosed among 20 HIV-negative patients living in Norway. Of these, 19 were immigrants from East Africa and one was an ethnic Norwegian. We wanted to find out if transmission had taken place in Norway or abroad and to identify the genetic basis of drug resistance. The strains were analyzed by IS6110 restriction fragment length polymorphism, antibiotic susceptibility tests, spoligotyping, reverse hybridization to regions of the rpoB gene, and sequencing of the katG gene. Epidemiological links between the patients were mapped, and the strains were compared to those isolated in 36 other countries and regions. All strains were resistant to isoniazid and carried Ala234Gly, Ser315Thr, and Arg463Leu substitutions in the katG gene. Eleven strains were MDR and carried a Ser531Leu substitution in the rpoB gene. MDR was acquired in the index patient after arrival in Norway. Links were found among 14 patients. The strain was imported from Somalia but acquired MDR and was transmitted in Norway. This demonstrated that MDR strains are not necessarily imported from high-incidence countries and can be highly communicable. The outbreak underscores a deficiency in the TB control measures employed in many countries and challenges the adequacy of the policy of screening immigrants for TB only on arrival.     

Inhibition of thymopoiesis of CD34+ cell maturation by HIV-1 in an in vitro CD34+ cell and thymic epithelial organ culture model

The mechanisms by which HIV-1 affects thymopoiesis were determined by preincubating CD34+ cells or cultured thymic epithelial (CTE) cells with lymphotropic (T-) and monotropic (M-) strains of HIV-1 in an in vitro CTE organ and CD34+ cell coculture model that allows for analysis of development of thymocytes and mature T cells. When purified CD34+ cells were precultured with either T- or M-tropic strains of HIV-1, thymopoiesis was impaired in a two-week coculture manifested by decreased cell number of thymocytes generated. However, the percentages of thymocyte subpopulations were comparable to control uninfected cocultures. Furthermore, HIV infection of thymocytes was predominantly observed in the CD44+CD3- population. However, in a four-week coculture experiment, HIV infection and depletion of more mature thymocytes were also observed. When CTE cells were preincubated with T- and M-tropic strains of HIV before addition of CD34+ cells, the number of thymocytes and subpopulations of thymocytes at early and later stages of maturation were markedly decreased. Furthermore, CD34+ and CD44+CD3- cells become HIV-infected. In summary, HIV-1 infection inhibited thymocyte maturation at early stages of thymocyte maturation CD44+CD25-CD3-. In addition, HIV also depleted later stages of CD4+ thymocyte subpopulations.     

Increased sensitivity to IL-4 in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a heightened Th2 CD4+ T-cell response to Aspergillus fumigatus allergens and a hyper-immunoglobulin (Ig)E state compared with cystic fibrosis patients without ABPA. We hypothesize that one reason for this response is increased sensitivity to interleukin (IL)-4 in ABPA resulting in increased expression of CD23 and CD86 and leading to a positive amplification mechanism that increases Th2 CD4+ T cell responses. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from seven ABPA CF and 19 non-ABPA CF patients and 16 nonatopic controls and stimulated with rIL-4 (range 0.1-10 ng/ml) and rIL-13 (range 1-10 ng/ml) for 48 h. The number of CD23 molecules and percentages of CD23+ B cells were quantified by flow cytometry. Both phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO) and antigen stimulated, toxoid and Asp f2/f3/f4, PBMC were examined for cytoplasmic cytokine synthesis enumerated by cytokine staining using flow cytometry to measure Th2 and Th1 CD3+ T cells. RESULTS: The numbers of CD23 molecules on B-cells were significantly elevated at time 0 in ABPA CF patients compared with both non-ABPA CF patients and nonatopic controls. Following IL-4 stimulation in vitro, the numbers and percentages of CD23 expression on B cells were significantly up-regulated in ABPA CF patients compared with non-ABPA CF patients and controls. The IL-13 stimulation up-regulated CD23 expression; however, there was no significant difference in ABPA CF patients compared with non-ABPA CF patients and controls. The percentages of interferon (IFN)-gamma+ CD3+T cells following PMA/IO stimulation were significantly decreased in both ABPA and non-ABPA CF patients compared with controls. There were no significant differences of IL-4+ and IL-13+ CD3+ T cells between ABPA and non-ABPA CF patients. When tetanus toxoid stimulated T cells were examined, both ABPA and non-ABPA CF patients had significantly decreased IFN-gamma+ CD3+ T cells compared with controls. In Asp f2/f3/f4 stimulated T cells, ABPA CF patients had significantly increased IL-4+ CD3+ T cells compared with non-ABPA CF patients and controls. CONCLUSIONS: ABPA CF patients have increased sensitivity to IL-4 but not to IL-13 up-regulation of CD23 molecules compared with non-ABPA CF patients. There were decreased percentages of IFN-gamma+ and IL-2+ Th1 T cells in CF patients compared with nonatopic controls but similar percentages of IL-4+ Th2 T cells in all three groups. However, ABPA CF patients had increased frequency of Aspergillus-stimulated Th2 T cells. This indicated that there is skewing of Th2 T cells in ABPA CF patients. Thus, in CF ABPA patients there is increased Th2 T cells and increased sensitivity to IL-4.     

Allergy: a systemic disease? The HUNT and Young–HUNT study,Norway.

A systemic nature of allergic diseases has been hypothesized. As part of this discussion, we studied if adolescent allergic wheeze and increasing combinations of allergic organ involvements (lung, nose and skin) would also increase the reporting of other health problems (headache, muscle pain and abdominal pain). In addition, we studied if parental asthma was associated with adolescent clustering of allergic expressions and if parental asthma with additional health problems (headache or muscle pain) was associated with adolescent reporting allergy in combination with headache, muscle pain and abdominal pain. Adolescents 13–19 yr (n = 8817, 89%) participated in the Young–HUNT study, Norway, 1995–97. Parental data on asthma were eligible in n = 5620. Health and lifestyle were measured by questionnaires and interviews. Associations with additional health problems were significantly strengthened with combinations of wheeze and other allergic expressions. Odds Ratio for associations ‘wheeze only’, ‘wheeze and rhinitis’ and ‘wheeze, rhinitis and eczema’ were for headache 2.1, 3.4 and 3.7; for muscle pain 2.8, 3.2 and 4.9; for abdominal pain 3.6, 4.0 and 4.9. All p for trend were <0.010. Similar results were obtained when studying allergic wheeze; p for trend <0.001. Parental asthma was associated with clustering of adolescent allergic expressions, and parental asthma with headache or muscle pain was significantly associated with reported allergy combined with similar health problems in their offspring. The results indicate that allergy may be expressed beyond organs commonly viewed as part of an allergic disease, and hence may support a hypothesis of a systemic nature of allergic diseases.