A randomised controlled trial of the monoaminergic stabiliser (-)-OSU6162 in treatment of myalgic encephalomyelitis/chronic fatigue syndrome.

OBJECTIVE: The monoaminergic stabiliser (-)-OSU6162 has in previous studies shown promising effects on mental fatigue after stroke and traumatic brain injury. This study investigated the safety and effectiveness of (-)-OSU6162 in patients with myalgic encephalomyelitis/chronic fatigue syndrome. METHODS: A total of 62 patients were randomly assigned to placebo or (-)-OSU6162. Primary outcomes were assessment on the mental fatigue scale (MFS) and the clinical global impression of change (CGI-C) scale. Secondary outcomes were results on the FibroFatigue scale (FF), the Beck Depression Inventory (BDI), the pain visual analogue scale and neuropsychological tests. Assessments were performed at baseline, after 1 and 2 weeks of treatment and at follow-up after 6 weeks. RESULTS: MFS and CGI-C showed significant improvements for both treatment groups after treatment but not at follow-up; a similar pattern was seen for FF and BDI. However, significant differences between groups could not be demonstrated. On the other hand, correlation analyses showed a significant correlation between (-)-OSU6162 concentration and change in MFS, FF, and BDI score within the concentration interval 0.1-0.7 µM. Exploratory subgroup analyses showed a larger treatment effect with (-)-OSU6162 in improving MFS and FF symptoms in patients on antidepressant therapy compared to those without antidepressant treatment. CONCLUSION: (-)-OSU6162 was found to be safe and well tolerated. When analysing the entire material (-)-OSU6162 was not found to differ significantly from placebo in alleviating fatigue in ME patients but was superior to placebo in counteracting fatigue in a subgroup of ME patients who received concomitant pharmacological treatment for depression.

Response to vitamin B12 and folic acid in myalgic encephalomyelitis and fibromyalgia.

BACKGROUND: Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders. OBJECTIVE: To evaluate clinical data from patients with ME, with or without fibromyalgia, who had been on B12 injections at least once a week for six months and up to several years. METHODS: 38 patients were included in a cross-sectional survey. Based on a validated observer's rating scale, they were divided into Good (n = 15) and Mild (n = 23) responders, and the two groups were compared from various clinical aspects. RESULTS: Good responders had used significantly more frequent injections (p<0.03) and higher doses of B12 (p<0.03) for a longer time (p<0.0005), higher daily amounts of oral folic acid (p<0.003) in good relation with the individual MTHFR genotype, more often thyroid hormones (p<0.02), and no strong analgesics at all, while 70% of Mild responders (p<0.0005) used analgesics such as opioids, duloxetine or pregabalin on a daily basis. In addition to ME, the higher number of patients with fibromyalgia among Mild responders was bordering on significance (p<0.09). Good responders rated themselves as "very much" or "much" improved, while Mild responders rated "much" or "minimally" improved. CONCLUSIONS: Dose-response relationship and long-lasting effects of B12/folic acid support a true positive response in the studied group of patients with ME/fibromyalgia. It's important to be alert on co-existing thyroid dysfunction, and we suspect a risk of counteracting interference between B12/folic acid and certain opioid analgesics and other drugs that have to be demethylated as part of their metabolism. These issues should be considered when controlled trials for ME and fibromyalgia are to be designed.

Murine gammaretrovirus group G3 was not found in Swedish patients with myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia.

BACKGROUND: The recent report of gammaretroviruses of probable murine origin in humans, called xenotropic murine retrovirus related virus (XMRV) and human murine leukemia virus related virus (HMRV), necessitated a bioinformatic search for this virus in genomes of the mouse and other vertebrates, and by PCR in humans. RESULTS: Three major groups of murine endogenous gammaretroviruses were identified. The third group encompassed both exogenous and endogenous Murine Leukemia Viruses (MLVs), and most XMRV/HMRV sequences reported from patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Two sensitive real-time PCRs for this group were developed. The predicted and observed amplification range for these and three published XMRV/HMRV PCRs demonstrated conspicuous differences between some of them, partly explainable by a recombinatorial origin of XMRV. Three reverse transcription real-time PCRs (RTQPCRs), directed against conserved and not overlapping stretches of env, gag and integrase (INT) sequences of XMRV/HMRV were used on human samples. White blood cells from 78 patients suffering from ME/CFS, of which 30 patients also fulfilled the diagnostic criteria for fibromyalgia (ME/CFS/FM) and in 7 patients with fibromyalgia (FM) only, all from the Gothenburg area of Sweden. As controls we analyzed 168 sera from Uppsala blood donors. We controlled for presence and amplifiability of nucleic acid and for mouse DNA contamination. To score as positive, a sample had to react with several of the XMRV/HMRV PCRs. None of the samples gave PCR reactions which fulfilled the positivity criteria. CONCLUSIONS: XMRV/HMRV like proviruses occur in the third murine gammaretrovirus group, characterized here. PCRs developed by us, and others, approximately cover this group, except for the INT RTQPCR, which is rather strictly XMRV specific. Using such PCRs, XMRV/HMRV could not be detected in PBMC and plasma samples from Swedish patients suffering from ME/CFS/FM, and in sera from Swedish blood donors.

Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study.

BACKGROUND: Deficiencies of vitamin B-12, folic acid, and vitamin B-6-as defined by laboratory measures-occur in 10-20% of elderly subjects. The clinical significance remains unresolved. OBJECTIVE: The objective was to explore any association between vitamin status and vitamin treatment and movement and cognitive performance in elderly subjects. DESIGN: Community-dwelling subjects (n = 209) with a median age of 76 y were randomly assigned to daily oral treatment with 0.5 mg cyanocobalamin, 0.8 mg folic acid, and 3 mg vitamin B-6 or placebo (double blind) for 4 mo. Movement and cognitive performance tests were performed before and after treatment. RESULTS: A high plasma total homocysteine (tHcy) concentration (> or =16 micromol/L) was found in 64% of men and in 45% of women, and a high serum methylmalonic acid (MMA) concentration (> or =0.34 micromol/L) was found in 11% of both sexes. Movement time, digit symbol, and block design (adjusted for age, sex, smoking, and creatinine) correlated independently with plasma tHcy (P < 0.01, < 0.05, and < 0.01, respectively); the simultaneity index and block design correlated with serum MMA (P < 0.05 for both). Vitamin therapy significantly decreased plasma tHcy (32%) and serum MMA (14%). No improvements were found in the movement or cognitive tests compared with placebo. Neither vitamin therapy nor changes in plasma tHcy, serum MMA, serum vitamin B-12, plasma folate, or whole-blood folate correlated with changes in movement or cognitive performance. CONCLUSIONS: High plasma tHcy and serum MMA were prevalent and correlated inversely with movement and cognitive performance. Oral B vitamin treatment normalized plasma tHcy and serum MMA concentrations but did not affect movement or cognitive performance. This might have been due to irreversible or vitamin-independent neurocognitive decline or to an insufficient dose or duration of vitamins.

Social and medical risk indicators for 8-year mortality in a Swedish urban elderly population.

The aim of this study was to identify and evaluate social and medical risk indicators for mortality in an urban elderly population. Altogether 217 subjects (144 women and 73 men, mean age 78 years, range 69-96 years of age) participated in an examination 1990/91. Eighty-eight persons (55 women and 33 men) had died, and 129 subjects (89 women and 40 men) were alive January 1, 1999. Several risk indicators were found and those with the highest statistical explanatory power to predict mortality were: tremor, inability for heavy housework, a pathological second heart sound, low triceps skinfold, low diastolic blood pressure and decreased appetite. A multivariate model (MVM) utililizing both social and medical risk indicators, and a clinical model (CM) based on the judgement of a registered nurse identified 49 and 34%, respectively, of those who died during the 8-year period (n = 88). A third risk group, the intervention group, comprising individuals selected by either the MVM or CM models, identified 56% of those who died. The latter procedure could be used to define risk groups for mortality in future intervention studies. The combination of social and medical risk indicators in MVM, and a CM might be used in studies with larger sample sizes in order to increase the knowledge in this field.

A longitudinal study on changes of movement performance and their relation to medical conditions in a female population followed from age 70 to 78.

We described longitudinal changes of movement performance in a population-based sample of women followed from age 70 to 78. We also studied the cross-sectional relationships between medical conditions and movement performance at baseline, and longitudinal relationships between baseline medical conditions and changes of movement performance. Two hundred and thirty-four women aged 70 years participated in the baseline study, and 88 women participated in a follow-up study 8 years later. Movement performance was measured by an optoelectronic test, the postural-locomotor-manual (PLM) test, which objectively and precisely measures the subject's mobility of lower and upper extremities. Information on medical conditions including selected diseases and symptoms were obtained by self-report and/or by physical examination. Movement time (MT), an indicator of the overall movement performance of the PLM test, increased over 8 years. This change was mainly related to prolonged duration of the locomotor phase (walking forward), but not to the duration of the manual phase (goal-directed arm reaching). At baseline, poor PLM performance was related to hypertension, orthostatic hypotension, cerebrovascular diseases, chronic bronchitis, depression, arthritis, dizziness, chest pain, dyspnea, joint problems, leg pain, tiredness, number of diseases and number of symptoms at baseline. Increased MT during follow-up was associated with arthritis and dyspnea at baseline, and newly developed diseases during follow-up. Our study results indicated that 70-year-old women had a general slowing of their movement performance over 8 years. Age-related decrements of movement performance were more striking in the lower extremities than in the upper extremities. Arthritis and dyspnea at baseline, and incident diseases during follow-up were related to this age-related decline of movement performance.

Ninety-seven-year-old people: general presentation, and some general and medical characteristics from a Swedish population study.

This study--the first in a series of reports--is a description of some general and medical characteristics of 97-year-olds from the representative longitudinal Gerontological and geriatric population studies in Göteborg, Sweden. The sample comprised 117 females and 15 males, a total of 132 97-year-olds. The probands were examined in their homes, with an interview based on a questionnaire. Blood hemoglobin, blood glucose and serum cobolamines were analyzed with standard methods, as well as a detailed hematological analysis which will be reported separately. An examination by a nurse and a physician was completed, comprising also dental status, visual ability and a simple hearing test. Anthropometric measurements and ECG were performed, and blood pressure was measured. Judged from cross-sectional data from our population studies, many symptoms and conditions seem to have a higher prevalence at age 97 than at age 70 and 85, respectively, especially regarding visual impairment, oral dryness, and hearing and ECG abnormalities. On the other hand the prevalence of edentulousness was surprisingly low. We find this investigation important for several reasons, namely its comprising a total community sample at this very high age in an urban area. Furthermore, the subjects are survivors of a cohort of elderly investigated several times by us since 1971/72 at age 70. In some aspects these survivors seem to be an elite of elderly people.

Motor performance in relation to age, anthropometric characteristics, and serum lipids in women.

BACKGROUND: The relationships between motor performance and age, anthropometric characteristics, and serum lipids were studied in a population-based sample of women (N = 865). METHODS: Motor performance was measured by a precise laboratory test, the Postural-Locomotion-Manual test, using an optoelectronic technique. Anthropometric measurements included body mass index (BMI) and waist-to-hip ratio. Blood samples were drawn for the measurement of total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride concentrations. RESULTS: Motor performance deteriorated with age in a curvilinear way. High BMI, high waist-to-hip ratio, high triglycerides and low HDL cholesterol were all correlated to poor motor performance after adjustment for age, vascular disease, hypertension, diabetes, smoking, physical exercise, and some chronic diseases. Stepwise regression analyses showed that age, waist-to-hip ratio, triglycerides, HDL cholesterol, physical exercise, and vascular diseases were independent predictors of motor performance. CONCLUSIONS: High age, high waist-to-hip ratio, high triglycerides, and low HDL cholesterol were associated with poor motor performance in women. Monitoring abdominal adiposity and serum lipids in clinical work might help us to identify people with early motor impairment and to prevent more severe mobility disability.