Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome—a randomised controlled trial

We have previously conducted a small treatment study on staphylococcus toxoid in fibromyalgia (FM) and chronic fatigue syndrome (CFS). The aim of the present study was to further assess the efficacy of the staphylococcus toxoid preparation Staphypan Berna (SB) during 6 months in FM/CFS patients. One hundred consecutively referred patients fulfilling the ACR criteria for FM and the 1994 CDC criteria for CFS were randomised to receive active drug or placebo. Treatment included weekly injections containing 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.6 ml, 0.8 ml, 0.9 ml, and 1.0 ml SB or coloured sterile water, followed by booster doses given 4-weekly until endpoint. Main outcome measures were the proportion of responders according to global ratings and the proportion of patients with a symptom reduction of > or =50% on a 15-item subscale derived from the comprehensive psychopathological rating scale (CPRS). The treatment was well tolerated. Intention-to-treat analysis showed 32/49 (65%) responders in the SB group compared to 9/49 (18%) in the placebo group (P<0.001). Sixteen patients (33%) in the SB group reduced their CPRS scores by at least 50% compared to five patients (10%) in the placebo group (P< 0.01). Mean change score on the CPRS (95% confidence interval) was 10.0 (6.7-13.3) in the SB group and 3.9 (1.1-6.6) in the placebo group (P<0.01). An increase in CPRS symptoms at withdrawal was noted in the SB group. In conclusion, treatment with staphylococcus toxoid injections over 6 months led to significant improvement in patients with FM and CFS. Maintenance treatment is required to prevent relapse.     

Activities of Daily Living Ratings of Elderly People Using Katz‘ ADL Index and the GBS-M Scale

Instruments for measuring activities of daily living (ADL) are useful in estimating institutionalized elderly ill people's need of care. The aim of the present study was to investigate to what extent the GBS-M scale measures ADL status, as determined by Katz' ADL Index. Forty-two elderly patients in long-term care in a psychiatric hospital were rated independently using each of the two scales. The correlation coefficient between results of the ratings was r = 0.93, i.e., high scores on one of the scales gave high scores on the other scale. Fifty per cent of severely demented patients had maximal scores on measures of ADL.     

The growth-associated protein GAP-43 is increased in the hippocampus and in the gyrus cinguli in schizophrenia

Schizophrenia is a common and severe psychiatric disorder of unknown etiology. Numerous neuropathological studies have found subtle structural changes in limbic structures, especially medial temporal lobe structures and the gyrus cinguli. To test the hypothesis that synaptic disturbances are involved in the pathogenesis of schizophrenia, we studied the growth-associated protein 43 (GAP-43), a protein localized to presynaptic terminals, suggested to be involved in establishment and remodeling of synaptic connections, in postmortem brain tissue, using quantitative Western blotting immunohistochemistry. The material consisted of brain tissue from 17 schizophrenics (80±11 yr), diagnosed according to the DSM-III-R criteria, and 20 age-matched controls (75±13 yr). Quantitative analyses showed increased GAP-43 protein levels in schizophrenic compared to control brains, both in the hippocampus (2.43±0.78 vs 1.00±0.29; p<0.0001) and in the gyrus cinguli (1.52±0.21 vs 1.00±0.35; p<0.0001). Also by immuno-histochemistry, increased GAP-43 staining was found in schizophrenic compared with control brains, throughout all layers of the gyrus cinguli and the hippocampus. Anomalous synaptic sprouting and reorganization, with resultant “miswiring,” as well as a defect in synaptic pruning have been hypothesized to be pathogenetic factors in schizophrenia. We suggest that a decreased synaptic density, whether caused by disturbed development or damage/degeneration, may elicit a reactive synaptogenesis (reflected by an increase in GAP-43), which may be functional or anomalous. Synaptic pathology in the limbic system may be of importance in the development of psychotic symptoms in schizophrenia.     

Vitamin B12-induced reduction of platelet monoamine oxidase activity in patients with dementia and pernicious anaemia

Platelet monoamine oxidase (MAO) activity has previously been shown to be increased in patients with senile dementia of Alzheimer type (SDAT) and in patients with megaloblastic anaemia. Moreover, low serum B12 levels were found to be 4-5 times more frequent in SDAT compared with an unselected population of similar age. In the present investigation, platelet MAO activity was estimated in 14 SDAT patients with relatively low serum B12 levels and in 4 patients with pernicious anaemia. Before B12 therapy, platelet MAO activity was significantly increased in both patient groups compared with a control group. After B12 therapy, platelet MAO activity was significantly reduced in both patient groups to apparently normal levels. The present results show that B12 status is a controlling factor of platelet MAO activity and confirm that a significant connection exists between vitamin B12 deficiency and primary degenerative dementia disorders, such as SDAT.     

Biochemical changes in Dementia disorders of Alzheimer type (AD/SDAT)

In postmortem investigations of patients with dementia of Alzheimer type (AD/SDAT) (n = 14) the brain weight was significantly reduced when compared to controls (n = 16). In four AD/SDAT-brain parts investigated the concentrations of 5-hydroxy-tryptamine and noradrenaline were significantly reduced while 3-methoxy-4-hydroxyphenylglycol was significantly increased. In the caudate nucleus of the AD/SDAT-brains the concentrations of dopamine and homovanillic acid were significantly reduced. The activity of monoamine oxidase B was increased suggesting a proliferation of extra neuronal tissue in the AD/SDAT-brains. The activity of choline acetyl transferase was reduced in the four brain parts investigated, showing a general reduction in the acetylcholine system in the AD/SDAT-brains. The ganglioside concentration was significantly reduced suggesting a reduced density of nerve endings in the demented brains. The AD/SDAT-group was according to rating scales severely demented. Patients with an early onset of the dementia disease were more severely intellectually reduced and had more pronounced biochemical disturbances than those with a late onset of the dementia.     

No evidence for xenotropic murine leukemia-related virus infection in sweden using internally controlled multiepitope suspension array serology

Many syndromes have a large number of differential diagnoses, a situation which calls for multiplex diagnostic systems. Myalgic encephalomyelitis (ME), also named chronic fatigue syndrome (CFS), is a common disease of unknown etiology. A mouse retrovirus, xenotropic murine leukemia-related virus (XMRV), was found in ME/CFS patients and blood donors, but this was not corroborated. However, the paucity of serological investigations on XMRV in humans prompted us to develop a serological assay which cover many aspects of XMRV antigenicity. It is a novel suspension array method, using a multiplex IgG assay with nine recombinant proteins from the env and gag genes of XMRV and 38 peptides based on known epitopes of vertebrate gammaretroviruses. IgG antibodies were sought in 520 blood donors and 85 ME/CFS patients and in positive- and negative-control sera from animals. We found no differences in seroreactivity between blood donors and ME/CFS patients for any of the antigens. This did not support an association between ME/CFS and XMRV infection. The multiplex serological system had several advantages: (i) biotinylated protein G allowed us to run both human and animal sera, which is essential because of a lack of XMRV-positive humans; (ii) a novel quality control was a pan-peptide positive-control rabbit serum; and (iii) synthetic XMRV Gag peptides with degenerate positions covering most of the variation of murine leukemia-like viruses did not give higher background than nondegenerate analogs. The principle may be used for creation of variant tolerant peptide serologies. Thus, our system allows rational large-scale serological assays with built-in quality control.     

The closure of a mental hospital in Sweden: Characteristics of patients in long-term care facing relocation into the community

Summary A political decision to decentralize psychiatric care in a county of Sweden was made in October 1984, leading to the closure of the only large mental hospital in the area (290,000 inhabitants). The hospital is of the traditional type, with 490 beds and 1,294 staff members. It has units for long-term care, short-term care and rehabilitation and a unit for research and education. The long-term care is to cease completely and be replaced by community based alternative types of care. In this study, the long-term population (n=199) was characterized and their levels of functioning were measured. The results showed that 91% of the patients were 65 years old or more and that more than half of them were organically demented. Only 20% were chronic schizophrenics. All patients were cognitively impaired and 80% were also impaired in ADL functioning. A correlation between length of stay in hospital and ADL functioning was found in the organically demented group, but not in the group of chronic psychiatrically ill patients. Thirty-nine per cent of the population were severely impaired in ADL functioning and needed nursing care around the clock; 34% were moderately impaired and needed help and support that could be given in alternative types of care; 27% were not impaired at all to midly impaired and could be relocated to some type of service apartment. Thus, all patients needed sheltered living arrangements and care provided by staff with adequate training.     

Reduction of the synaptophysin level but normal levels of glycerophospholipids in the gyrus cinguli in schizophrenia

The 'membrane hypothesis' of schizophrenia postulates a disturbance in the metabolism and structure of membrane phospholipids resulting in a disturbance in the function of neuronal membrane proteins. Most studies exploring this hypothesis have examined components of peripheral blood. Since it may be questioned if these peripheral measurements reflect changes in the brain, we studied the fatty acid composition of glycerophospholipids in brain tissue. As a marker for synaptic density, we also measured the synaptic vesicle protein synaptophysin. Brain tissue (gyrus cinguli) from 11 schizophrenic patients (mean age 80 +/- 10 years) and 13 controls (mean age 75 +/- 14 years) was examined. The glycerophospholipid fatty acids were determined by gas chromatography. Synaptophysin protein level was determined using quantitative immunoblotting followed by Western blotting. There were no significant differences between the groups in the total or in any individual level of fatty acids, either in the n - 6 or n - 3 series. The level of synaptophysin was significantly p = (0.002) decreased in the schizophrenic group(0.73 + 0.18) as compared with the control group (1.02 + 0.21). The normal pattern and concentration of glycerophospholipids fatty acids found in the present study do not support the membrane hypothesis of schizophrenia. The possibility of a type II error should, however. be considered. On the other hand, the reduced synaptophysin' levels in the gyrus cinguli demonstrate that biological differences can be revealed in this relatively small sample. This also lends further support to the notion that a synaptic disturbance or loss is of importance in the pathogenesis of schizophrenia.     

Transcobalamin polymorphism and serum holo-transcobalamin in relation to Alzheimer's disease

Isoforms of the vitamin B(12) carrier protein transcobalamin (TC) might influence its cellular availability and contribute to the association between disrupted single-carbon metabolism and Alzheimer's disease (AD). We therefore investigated the relationships between the TC 776C>G (Pro259Arg) genetic polymorphism, total serum cobalamin and holo-TC levels, and disease onset in 70 patients with clinically diagnosed AD and 74 healthy elderly controls. TC 776C>G polymorphism was also determined for 94 histopathologically confirmed AD patients and 107 controls. Serum holo-TC levels were significantly higher in TC 776C homozygotes (p = 0.04). Kaplan-Meier survival functions differed between homozygous genotypes (Cox's F-Test F(42, 46) = 2.1; p = 0.008) and between 776C homozygotes and heterozygotes (Cox's F test F(46, 108) = 1.7; p = 0.02). Proportionately fewer TC 776C homozygotes appear to develop AD at any given age, but this will require confirmation in a longitudinal study.     

Subcortical symptoms predominate in vascular dementia

Thirty-one patients with the clinical diagnosis of vascualar dementia were examined with regard to symptoms reflecting disturbances in various brain regions. Frontal, parietal, subcortical and non-regional symptom complexes were used to characterize each patient. Frontal (77%) and subcortical (68%) symptoms were the most common clinical patterns. Using an overall evaluation, subcortical symptomatology was the most prominent clinical picture (45%) Extrapyramidal symptoms, an important aspect of the subcortical symptom complex, were associated with histories of hypertension (p<0.05) and low levels of 5-hydroxyindoleacetic acid (p<0.05) in the spinal fluid. This study suggests that subcortical, and possibly also frontal, symptoms are typical and perhaps underestimated manifestations of vascular dementia and that they may reflect important pathogenetic pathways in this disorder.