Multiple sclerosis is linked to Epstein-Barr virus infection

The aetiology and pathogenesis of MS are unknown, but environmental agents, genetic susceptibility and stochastic events are likely to be involved. In order to evaluate the possibility that MS is linked to EBV infection, we here evaluate studies on MS- and EBV-epidemiology, prospective and retrospective analysis of EBV-serology, investigations of EBV DNA sequences in blood and tissues, specificity of antibodies in oligoclonal bands in MS patients and results from antiviral chemotherapy of MS patients. It could be demonstrated that EBV is complying with the epidemiological observations in MS and that all MS patients are seropositive to EBV in contrast to healthy controls. Importantly, despite difficulties in diagnosing child-MS, the vast majority of these patients are also EBV seropositive. In contrast to control groups, recent EBV infections have never been observed in children or adults with MS. Further prospective studies indicate a 2.8 times higher tendency for development of MS after infectious mononucleosis. In MS patients, unbiased analyses pull out EBV antigens as high-affinity targets for the antibodies in the oligoclonal bands. Humans are the exclusive natural host for EBV, a finding that may explain why MS is unique to humans. Together these unique observations strongly suggest a linkage between MS and EBV infection. Infection by EBV offers numerable mechanisms to perturb the immune system, including mimicry and superantigen induction, which may potentially participate in the disease mechanisms. In contrast, studies demonstrating higher IgG titres and occurrence of viral DNA in serum/plasma are likely to reflect a consequence of the disease. An explanation for a potential role of respiratory diseases in MS is discussed. It is concluded that the ultimate test to the hypothesis of MS and EBV is the development and application of an EBV vaccine, which is predicted to eradicate the disease.     

Early detection of the first episode of schizophrenia and suicidal behavior

OBJECTIVE: The suicide rate in schizophrenia is high, with the risk being highest early in the course. The rate of suicide attempts before treatment onset is also high and is often the event leading up to first treatment contact. A previous report showed that the duration of untreated psychosis can be reduced through an early detection program, and that the reduction was associated with lower symptom levels at treatment initiation. Treatment programs that bring first-episode patients into treatment at lower symptom levels can have the potential to reduce risk for suicide attempts. METHOD: The authors examined consecutive patients with nonorganic, nonaffective psychosis who sought initial treatment at psychiatric treatment units in four catchment areas: two that had an early detection program and two that did not. RESULTS: The rate of severe suicidality (plans or attempts) was significantly higher in subjects from communities without the early detection program relative to those from early detection communities, even after adjustments for known predictors of suicidality. CONCLUSION: Early detection programs that bring patients into treatment at lower symptom levels may reduce suicidality risk at first treatment contact.     

The development of subjective quality of life over the first 2 years in first-episode psychosis

The main aim of this study was to examine changes in subjective quality of life (general s-QoL) in patients with first-episode psychosis from baseline to 2 years follow-up. A total of 201 of 252 patients had full quality of life assessment at both baseline and at 2 years. Repeated measure analyses of variance were done to evaluate the development over time, and multiple linear regression analyses to evaluate predictors of change. These patients with a first-episode psychosis showed a significant improvement in general s-QoL during the first 2 years of treatment. Improvements in general s-QoL were associated with increase in excitative symptoms and with improvements in depressive symptoms, global functioning, level of daily activities, level of social activities, and perceived general health.     

Substance abuse in first-episode non-affective psychosis

Abuse of alcohol and drugs is an important and clinically challenging aspect of first-episode psychosis. Only a few studies have been carried out on large-sized and reliably characterized samples. These are reviewed, and the results are compared with a sample of 300 first-episode psychosis patients recruited for the TIPS (Early Treatment and Identification of Psychosis) study from Norway and Denmark. Prevalence rates from the literature vary from 6% to 44% for drugs and 3% to 35% for alcohol. In our sample, 23% abused drugs and 15% abused alcohol during the last 6 months. When compared to non-abusers, the drug-abusing group is characterized by the following: male gender, younger age, better premorbid social, poor premorbid academic functioning, and more contact with friends in the last year before onset. Alcohol abusers were the oldest group and they had the least contact with friends. A group of patients abusing both drugs and alcohol had poor premorbid academic functioning from early childhood. Overall, drug and alcohol abuse are highly prevalent in contemporary first-episode psychosis samples. In our study, substance abuse comorbidity did not generate differences on diagnosis, duration of untreated psychosis, psychiatric symptoms, or global functioning at onset/baseline. The premorbid profiles of the substance abusers were clearly different from the non-abusers. Drug abusers, in particular, were more socially active both premorbidly and during the year preceding the start of treatment.     

Plasma concentration of hGH and anti-hGH antibodies after subcutaneous administration of hGH for 3 weeks to immunosuppressed pigs.

OBJECTIVE: The objective of the present study was to evaluate the dosing regimen of immunosuppressants necessary to avoid the formation of anti-hGH antibodies in a pig model. ANIMALS: Sixteen pigs were divided into four groups. PROCEDURE: Three different immunosuppressive treatments were tested (group 1: Control (no treatment); group 2: 10 mg; group 3: 20 mg; and group 4: 40 mg cyclosporine; combined with 2 mg azatioprine and 2 mg prednisolone p.o./kg/day). The treatments were given from days -7 to 22. All groups were dosed subcutaneously (s.c.) with 0.5 mg hGH/kg once daily from days 1 to 22. On the first and the last days of dosing blood samples were collected to describe the hGH concentration versus time profile. Before dosing and on days 5, 10, and 15 blood samples were collected for measuring hGH antibody formation. RESULTS: A dose-dependent decrease in white blood cell counts was observed in all immunosuppressive-treated groups. Groups 1 and 2 produced antibodies against hGH during the 22 days of dosing while the formation of antibodies was suppressed in groups 3 and 4. In the control group and group 2 the pharmacokinetic parameters of hGH were influenced by the formation of anti-hGH antibodies. In groups 3 and 4, the pharmacokinetic parameters were comparable on the first and the last day of dosing. CONCLUSION: The formation of anti-hGH antibodies influenced the pharmacokinetics of hGH in pigs, but it could be prevented by immunosuppressive therapy. From the present experiment, a dose of 20 mg cyclosporine, 2 mg azatioprine, and 2 mg prednisolone p.o./kg/day was able to prevent the pigs from producing antibodies without having severe adverse effects. This model may by useful in future experiments using sustained release formulations of hGH, and possibly for other compounds that may induce antibody production in pigs.     

Effect of physical exercise on in vitro production of interleukin 1, interleukin 6, tumour necrosis factor-alpha, interleukin 2 and interferon-gamma

The present study was designed to examine the effect of physical exercise on production of interleukin-1 (IL-1), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). Ten young, healthy volunteers underwent 60-min bicycle exercise at 75% of maximal oxygen uptake (VO2max). Blood samples were collected before and during the last minutes of exercise, as well as 2 h and 24 h later. Blood mononuclear cells (BMNC) were stimulated in vitro with either bacterial lipopolysaccharide or phytohaemagglutinin, and the supernatants were tested for the above-mentioned cytokines using bioassays as well as ELISA techniques. The production of IL-6 increased significantly 2 h after exercise, furthermore the production of IL-1 alpha and IL-1 beta was enhanced, although only borderline significant. TNF-alpha, IL-2 and IFN-gamma did not fluctuate in relation to exercise. The increased amounts of IL-1 and IL-6 in the supernatants generated from a fixed number of BMNC are most likely explained by the increased percentage and absolute number of blood monocytes 2 h after exercise. IL-2 and IFN-gamma are mainly produced by CD4+ and CD16+ cells. During exercise the CD4+ subset decreases, while the CD16+ subset increases. The finding of unchanged production of IL-2 and IFN-gamma was therefore expected.     

Differential effects of insulin detemir and neutral protamine Hagedorn (NPH) insulin on hepatic glucose production and peripheral glucose uptake during hypoglycaemia in type 1 diabetes

Aims/hypothesis  

We compared the symptoms of hypoglycaemia induced by insulin detemir (NN304) (B29Lys(ε-tetradecanoyl),desB30 human insulin) and equally effective doses of neutral protamine Hagedorn (NPH) insulin in relation to possible differential effects on hepatic glucose production and peripheral glucose uptake.