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Biomedical subjects

M Haugen

Publications and source records attributed to M Haugen.

At least 19 recordsLinked to original sources

Detection of autoantibodies to the BTB-kelch protein KLHL7 in cancer sera.

The aim of the study was to search for novel targets of autoantibodies in patients with paraneoplastic neurological syndromes (PNS). PNS are mediated by immune reactions against autoantigen(s) shared by the cancer cells and the nervous system. By serological screening of a rat cerebellum cDNA expression library using anti-Hu-positive sera from three patients with paraneoplastic encephalomyelitis (PEM), we identified an open reading frame encoding an isoform of the BTB-kelch protein KLHL7. Immunohistochemical studies demonstrated that the KLHL7 protein is expressed in the nuclei of neurones, but not in other tissues including various cancers. However, the KLHL7 protein was detected in the nuclei of cancer cell lines. Antibodies to KLHL7 were detected by an immunoprecipitation assay in sera from 12 of 254 (4.7%) patients with various cancers and 2 of 170 blood donors (1.2%). None of 50 sera from patients with multiple sclerosis were positive for KLHL7 antibodies. Sixteen patients with classical PNS and anti-Hu or anti-Yo antibodies were also negative for KLHL7 antibodies. Seven cancer patients with KLHL7 antibodies had various signs of neurological disease that could be related to cancer, whereas the remaining five seropositive cancer patients had no clinical signs of possible PNS. The present results indicate that KLHL7 antibodies are associated with various cancers, and in some patients also with neurological disease. Whether KLHL7 antibodies can be used as paraneoplastic markers for PNS remains to be determined.

Amino Acid Sequence↗

Dietary intake of differently fed salmon; the influence on markers of human atherosclerosis.

BACKGROUND: Cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs) of marine origin are well recognized. Because of the shortness of marine resources vegetable oils are increasingly used in fish farming. The effects on human health of fish fed on vegetable oils are largely unknown. METHODS: In a double-blinded intervention study, 60 patients with coronary heart disease (CHD) were randomly allocated to three groups consuming approximately 700 g per week for 6 weeks of differently fed Atlantic salmon: 100% fish oil (FO), 100% rapeseed oil (RO) or 50% of each (FO/RO), resulting in fillets with high, intermediate and low levels of marine n-3 PUFAs. Patient analyses before and after the intervention period included serum fatty acid profile, serum lipoproteins, and markers of vascular inflammation. RESULTS: The serum fatty acid profiles of the patients after the intervention mirrored those of the corresponding salmon fillets and the respective salmon feeds. Significant differences between the groups were obtained, especially for the levels of total n-3 PUFAs and the n-3/n-6 FA ratio, which were markedly increased in the FO group in contrast to the two other groups (P < 0.02 for all). Additionally, significant reductions of serum triglycerides and of vascular cell adhesion molecule-1 and interleukin-6 were obtained in patients receiving the FO diet when compared with the two other groups (P < 0.05 for all). CONCLUSIONS: Tailor-made Atlantic salmon fillets very high in n-3 PUFAs of marine origin seem to impose favourable biochemical changes in patients with CHD when compared with ingestion of fillets with intermediate and low levels of marine n-3 PUFAs, when replaced by rapeseed oil.

Aged↗

Hu and voltage-gated calcium channel (VGCC) antibodies related to the prognosis of small-cell lung cancer.

PURPOSE: Hu antibodies previously have been associated with longer survival of patients with small-cell lung cancer (SCLC). Voltage-gated calcium channel (VGCC) antibodies play a pathogenic role in Lambert Eaton myasthenic syndrome, which is also associated with SCLC. These antibodies may reduce tumor growth in patients with the neurologic disease, but it is not clear whether they provide prognostic information in those without neurologic symptoms. PATIENTS AND METHODS: Two hundred patients with SCLC (age 39 to 79 years; mean, 62.3 years; 129 males and 71 females) receiving chemotherapy were studied for the presence of Hu and VGCC antibodies. Sera were examined for Hu antibodies by an in vitro transcription-translation-based immunoprecipitation technique and by immunohistochemistry/dot blot. VGCC (P/Q subtype) antibodies were detected by radioimmunoassay. Survival analysis was used to analyze the data. Results Hu antibodies were detected in 51 of 200 patients (25.5%) by in vitro transcription-translation-based immunoprecipitation and in 37 of 200 patients (18.5%) by immunohistochemistry or dot blot, whereas VGCC antibodies were detected in only 10 of 200 patients (5%). The presence of Hu antibodies did not correlate with VGCC antibodies, and there was no association between Hu or VGCC antibodies and the extent of disease or survival. CONCLUSION: Hu and VGCC antibodies are found in a proportion of SCLC patients, irrespective of neurologic symptoms, but their presence does not correlate with the prognosis of the SCLC.

Adult↗

Health status in fibromyalgia--a followup study.

OBJECTIVE: To examine symptoms, physical function, and nutritional status in patients with fibromyalgia (FM) after 6 to 8 years. METHODS: Of 51 women with FM initially included in exercise and patient education programs 6 and 8 years ago, 33 agreed to participate. Median (range) age was 45.5 years (33-64) and symptom duration 18 years (8-46). Symptoms (visual analog scales), cardiovascular capacity (Aastrand's test), and restriction on daily activities (Fibromyalgia Impact Questionnaire) were measured. Employment status and experience of coping with everyday life were addressed in an interview. Nutritional status was evaluated by anthropometric measurements and dietary intake. RESULTS: All the 33 participants had widespread chronic pain, and 79% had enough tender points to satisfy the FM classification criteria. Compared with initital data there were significant reductions in the number of tender points (p = 0.004) in the exercise group, and in fatigue (p = 0.008) and pain (p = 0.5) in the patient education group. Cardiovascular capacity was within normal limits in 33% of the participants. Currently, 26 performed regular physical activity and of these, 10 were engaged in organized exercise. Seventy-two percent reported regular use of dietary supplements and attached importance to a healthy diet. Still, there was a significant increase in weight and body fat, and 24% were obese (BMI > 30). The coping strategies adopted were adjustments to the new situation and distraction from symptoms. CONCLUSION: No worsening of symptoms and no change in employment status, as well as frequent participation in physical activities, suggests a benign longterm outcome in these patients with FM.

Activities of Daily Living↗

Young adults with juvenile arthritis in remission attain normal peak bone mass at the lumbar spine and forearm.

OBJECTIVE: To assess the impact of disease activity on acquired peak bone mass and bone turnover in young adult patients with either persistent juvenile arthritis (JA) or a history of JA (JA in remission). METHODS: Two hundred twenty-nine patients with JA were studied after a mean +/- SD of 15.6 +/- 2.4 years in women and 14.9 +/- 2.1 years in men since disease onset. One hundred forty-five women and 84 men were over the age of 20 at the time of examination (mean +/- SD age 24.9 +/- 2.9 years for women and 25.2 +/- 3.1 years for men). Forty-one healthy women (mean +/- SD age 27.4 +/- 3.1 years) and 55 healthy men (mean +/- SD age 25.7 +/- 3.1 years) served as a reference group. Bone mineral density (BMD) was analyzed by dual x-ray absorptiometry. Serum osteocalcin concentrations and urinary concentrations of deoxypyridium (D-Pyd) were measured. Linear regression analyses were performed to evaluate the impact of disease on BMD. RESULTS: Patients with persistent disease had significantly lower BMD compared with healthy subjects (P < 0.001 for women at all measured sites and for men at the femoral neck and total body; P < 0.05 for men at the radius and lumbar spine). Of the patients with a history of JA, only women had significantly lower BMD at the femoral neck and total body (P < 0.05). Patients with persistent JA had significantly more osteopenia and osteoporosis than healthy subjects, while patients with a history of JA had more frequent osteopenia only in the total body. Weight, urinary concentration of D-Pyd, and belonging to the patient group significantly affected BMD at all measured sites in the entire study population, while analysis of all patients found that only the number of months taking corticosteroids significantly affected BMD at all measured sites. However, the impact of the variables differed from site to site. CONCLUSION: Our findings imply that most young adults with JA attain the same BMD as healthy subjects if the disease goes into remission, while young adults with active disease have increased risk for osteopenia and osteoporosis.

Absorptiometry, Photon↗

New treatment possibilities in rheumatoid arthritis.

It is very difficult to predict future treatment modalities especially in diseases like rheumatoid arthritis (RA) with unknown etiology and pathogenesis. In the near future, traditional disease-modifying antirheumatic drugs (DMARD) alone, in combination with each other, or together with cyclosporine, FK506, Rapamycin, or Leflunomide, will probably be the main treatment for RA. Currently biological anti-TNFalpha agents like humanized MAb and recombinant TNF-receptor constructs are now launched in the market. This therapy alone, or in combination with methotrexate is very effective in RA patients. There are, however, concerns over increase in serious infections. Autologous stem cell transplantation will probably be used in certain patient with serious autoimmune diseases.

Arthritis, Rheumatoid↗

Effective state EMS lobbying: it's all in the plan.

Any piece of legislation needs grass roots support. If local legislators are not hearing from local EMS systems, the bill will have an uphill battle in the legislative assembly. Bill sponsors and key supporters need to be regularly informed of the bill's status. Remember the KISS theory--all testimony and communication between local EMS lobbyists and legislators needs to be kept at an understandable level. Finally, remember to never quit your lobbying until the Governor signs the bill into law.

Emergency Medical Services↗

Assessment of nutritional status in patients with rheumatoid arthritis and osteoarthritis undergoing joint replacement surgery.

OBJECTIVE: To evaluate pre- and postoperative nutritional status in patients with rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Preoperative dietary intake was assessed by a food frequency questionnaire, and postoperative dietary intake by food records. Anthropometric and laboratory measurements were assessed 1 day before and 10 days after surgery. Disease activity and acute response to surgery were assessed by erythrocyte sedimentation rate and G-reactive protein. RESULTS: The dietary intake was similar in the two groups preoperatively. Energy, protein, and fluid intake was significantly higher in the RA group postoperatively. There was a significant reduction in the concentration of hemoglobin, albumin, total protein, and ferritin in the OA group after surgery, whereas only hemoglobin concentration was reduced in the RA group. CONCLUSION: Preoperative nutritional status in the RA group was reduced as compared with preoperative nutritional status in the OA group. However, nutritional status in the RA group was less affected after joint replacement surgery compared with nutritional status in the OA group.

Adult↗

Rheumatoid arthritis and metal compounds--perspectives on the role of oxygen radical detoxification.

Rheumatoid arthritis (RA) is characterised by migration of activated phagocytes and other leukocytes into synovial and periarticular tissue. Activated oxygen species and other mediating substances from triggered phagocytes appear to exacerbate and perpetuate the rheumatoid condition. Iron excesses are capable of aggravating the arthritic inflammation, probably through their pro-oxidant potentials. In contrast, therapeutically given gold salts, through a lysosomal loading of the metal, inhibit the triggered cells, thereby reducing the toxic oxygen production. Pharmacological doses of zinc also may immobilise macrophages. Furthermore, the copper-zinc-containing enzyme SOD (superoxide dismutase) can act as a scavenger of toxic oxygen in the tissues. Therapeutic remission of RA has been obtained following intraarticular administration of SOD. Intramuscular administration of copper complexes has induced remission in about 60% of RA patients in open studies. Another drug, penicillamine, that protects cellular membranes against toxic oxygen in vitro, is presumed to act as an antirheumatic via the SOD mimetic activity of its copper complex. Thiomalate and other thiols may possess similar activities. Selenium compounds also may act as oxygen radical scavengers. A significant alleviation of articular pain and morning stiffness was obtained following selenium and vitamin E supplementation in a double-blind study on RA patients. The observations reviewed here indicate that metal compounds and other antioxidants can reduce the rheumatic inflammation by reducing the cellular production and/or concentration of toxic oxygen species.

Arthritis, Rheumatoid↗

Multidisciplinary approach to fibromyalgia. A pilot study.

The aim of the study was to instruct a group of fibromyalgia patients how to solve problems related to activities of daily life. Sixteen female fibromyalgia patients completed a ten week multidisciplinary program, consisting of a cognitive and an exercise part. After ten weeks a reduction in general pain intensity (p < 0.05) was found. At six months follow-up sensory (somatic) pain intensity was reduced compared to baseline recordings (p = 0.05). All patients had made adjustments to their everyday life after ten weeks. Eight patients reported that they regularly practised relaxation techniques, and seven patients had undertaken dietary changes. Thus, the study shows that adjustment of activities in daily living may reduce pain in patients with fibromyalgia. Controlled studies are needed in the future.

Activities of Daily Living↗

Decrease in anti-Proteus mirabilis but not anti-Escherichia coli antibody levels in rheumatoid arthritis patients treated with fasting and a one year vegetarian diet.

OBJECTIVE: To measure Proteus mirabilis and Escherichia coli antibody levels in patients with rheumatoid arthritis (RA) during treatment by vegetarian diet. METHODS: Sera were collected from 53 RA patients who took part in a controlled clinical trial of fasting and a one year vegetarian diet. P mirabilis and E coli antibody levels were measured by an indirect immunofluorescence technique and an enzyme immunoassay, respectively. RESULTS: The patients on the vegetarian diet had a significant reduction in the mean anti-proteus titres at all time points during the study, compared with baseline values (all p < 0.05). No significant change in titre was observed in patients who followed an omnivorous diet. The decrease in anti-proteus titre was greater in the patients who responded well to the vegetarian diet compared with diet non-responders and omnivores. The total IgG concentration and levels of antibody against E coli, however, were almost unchanged in all patient groups during the trial. The decrease from baseline in proteus antibody levels correlated significantly (p < 0.001) with the decrease in a modified Stoke disease activity index. CONCLUSION: The decrease in P mirabilis antibody levels in the diet responders and the correlation between the decrease in proteus antibody level and decrease in disease activity supports the suggestion of an aetiopathogenetic role for P mirabilis in RA.

Antibodies, Bacterial↗

Changes in laboratory variables in rheumatoid arthritis patients during a trial of fasting and one-year vegetarian diet.

We have previously reported that significant improvement may be obtained in rheumatoid arthritis patients by fasting followed by a vegetarian diet for one year. The present study was carried out to examine to what extent biochemical and immunological variables changed during the clinical trial of fasting and vegetarian diet. For the patients who were randomised to the vegetarian diet there was a significant decrease in platelet count, leukocyte count, calprotectin, total IgG, IgM rheumatoid factor (RF), C3-activation products, and the complement components C3 and C4 after one month of treatment. None of the measured parameters changed significantly during this period in the group of omnivores. The course of 14 of 15 measured variables favored the vegetarians compared with the omnivores, but the difference was only significant for leukocyte count, IgM RF, and the complement components C3 and C4. Most of the laboratory variables declined considerably in the vegetarians who improved according to clinical variables, indicating a substantial reduction in inflammatory activity. The leukocyte count, however, decreased in the vegetarians irrespective of the clinical results. Thus, the decline in leukocyte count may be attributed to vegetarian diet per se and not to the reduction in disease activity. The results of the present study are in accordance with the findings from the clinical trial, namely that dietary treatment can reduce the disease activity in some patients with rheumatoid arthritis.

Adult↗

Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet.

We have previously reported that a significant improvement can be obtained in rheumatoid arthritis patients by fasting followed by an individually adjusted vegetarian diet for one year. The patients who changed their diet could be divided into diet responders and diet nonresponders. After the clinical trial the patients were free to change diet or medication and after approximately one year they were asked to attend a new clinical examination. We compared the change from baseline (i.e. at the time of study entry) to the time of the follow-up examination for diet responders, diet nonresponders and controls who ate an omnivorous diet. The following variables favoured diet responders: pain score, duration of morning stiffness, Stanford Health Assessment Questionnaire index, number of tender joints, Ritchie's articular index, number of swollen joints, ESR and platelet count [corrected]. The difference between the three groups were significant for all the clinical variables, except for grip strength. There was no significant difference between the groups with regard to laboratory or anthropometric variables. At the time of the follow-up examination all diet responders but only half of the diet nonresponders still followed a diet. Our findings indicate that a group of patients with rheumatoid arthritis benefit from dietary manipulations and that the improvement can be sustained through a two-year period.

Adult↗

Vegetarian diet for patients with rheumatoid arthritis: can the clinical effects be explained by the psychological characteristics of the patients?

In a controlled, single blind clinical trial we have demonstrated recently a beneficial effect of fasting and vegetarian diet in RA. In the present study we compared 53 patients who participated in this clinical trial with 71 other RA patients with regard to some psychological parameters. The patients who participated in the clinical trial differed significantly from other RA patients. Firstly, they had a higher internal score and a lower chance score on the Multi-dimensional Health Locus of Control Scale (MHLCS). Secondly, their belief in the effect of ordinary medical treatment, evaluated by a 10-cm visual analogue scale, was lower, and their belief in the effect of 'alternative', unconventional forms of treatment was higher. Of the patients who were randomized to a vegetarian diet, there was no significant difference between diet responders and diet non-responders with regard to the MHLCS scores. But, diet responders had a significantly lower belief in the effect of ordinary medical treatment compared with diet non-responders. The psychological distress imposed on the patients by changing from an omnivorous diet to a vegetarian diet was monitored during the clinical trial by means of the General Health Questionnaire. Throughout the clinical trial, this variable favoured the vegetarians compared with the omnivorous and the diet responders vs the diet non-responders. We conclude, firstly, that patients with certain psychological characteristics were selected to the clinical trial; secondly, that the MHLCS scores could not explain the clinical improvement, but it may have been influenced by the patients' beliefs in ordinary and 'alternative' forms of treatment; and thirdly, that dietary treatment decreased psychological distress.

Adult↗

Changes of faecal flora in rheumatoid arthritis during fasting and one-year vegetarian diet.

The beneficial effect of a 1-yr vegetarian diet in RA has recently been demonstrated in a clinical trial. We have analysed stool samples of the 53 RA patients by using direct stool sample gas-liquid chromatography of bacterial cellular fatty acids. Based on repeated clinical assessments disease improvement indices were constructed for the patients. At each time point during the intervention period the patients in the diet group were then assigned either to a group with a high improvement index (HI) or a group with a low improvement index (LI). Significant alteration in the intestinal flora was observed when the patients changed from omnivorous to vegan diet. There was also a significant difference between the periods with vegan and lactovegetarian diets. The faecal flora from patients with HI and LI differed significantly from each other at 1 and 13 months during the diet. This finding of an association between intestinal flora and disease activity may have implications for our understanding of how diet can affect RA.

Arthritis, Rheumatoid↗

Repair of osteopenia in children with juvenile rheumatoid arthritis.

To test the hypothesis that the presence of osteopenia in juvenile rheumatoid arthritis is directly correlated with clinical disease activity and therefore reversible, we prospectively studied cortical bone mineral density (BMD) serially in 27 children. Twenty-four (89%) had BMD > or = 2 SD below age-related normal values (disease duration 49.3 +/- 7.7 months) at the beginning of the study. Of 27 children who had clinical disease improvement measured by a disease activity score during our study period, 17 (63%) had significant improvement or significant normalization, or both, of their BMD (0.34 +/- 0.13 gm/cm2 at initiation and 0.41 +/- 0.17 gm/cm2 at completion, p < 0.05; disease activity score of 3.4 +/- 0.2 at initiation and 1.4 +/- 0.2 at completion, p < 0.005). The increase in BMD was associated with a similar directional change in serum osteocalcin concentrations (4.6 +/- 1 ng/ml at initiation vs 9.1 +/- 1.1 ng/ml). The 10 patients whose disease became or remained active had a decreased or unchanged low serum osteocalcin level and BMD (BMD 0.37 +/- 0.17 gm/cm2 at initiation and 0.37 +/- 0.16 gm/cm2 at completion; disease activity score of 3.1 +/- 0.3 at initiation and 3.4 +/- 0.2 at study completion). We conclude that children with JRA who have improvement in their disease activity have an improvement in BMD heralded by an increase in serum osteocalcin values.

Adolescent↗