Factors of importance for weight loss in elderly patients with Parkinson's disease

OBJECTIVE: Weight loss is reported frequently in patients with Parkinson's disease (PD). The objective of this study was to find the underlying factors of this phenomenon. PARTICIPANTS AND METHODS: Twenty-six L-dopa-treated patients with PD and 26 age- and sex-matched healthy controls were assessed twice within a 1-year interval. Body weight, body fat mass, resting energy expenditure, physical activity, energy intake, thyroid hormones and cognitive function were investigated. RESULTS: Nineteen (73%) of the PD patients lost body weight, although energy intake and the time for rest increased. Weight loss was most marked in patients with more severe PD symptoms and in whom cognitive function had decreased. Multiple regression analyses showed that determinants for weight loss were female gender, age and low physical activity. CONCLUSION: Weight loss was common in PD patients, in spite of the increased energy intake and was most obvious in patients with increased PD symptoms and decreased cognitive function.     

Genetic heterogeneity of autoimmune disorders in the nonobese diabetic mouse

The nonobese diabetic mouse is highly susceptible not only to diabetes but to several autoimmune diseases, and one might suspect that these are controlled by a shared set of genes. However, based on various gene-segregation experiments, it seems that only a few loci are shared and that each disorder is influenced also by a unique set of genes.     

Levels of CD5+ B lymphocytes do not differ between patients with myasthenia gravis and healthy individuals.

CD5+ B cells might be involved in autoimmunity mainly as autoantibody-producing cells. To investigate the possible role of these cells in myasthenia gravis, we studied the numbers of CD5+ B cells, CD5- B cells, and CD19+ B cells as well as CD5+ T cells in the peripheral blood from 31 patients with myasthenia gravis and 31 healthy individuals. Both absolute percentages (percent of peripheral blood mononuclear cells) and relative percentages (percent of total CD19+ B cells) of CD5+ B cells were the same in patients as in controls. The numbers of CD5- B cells and CD19+ B cells were the same in both groups, whereas CD5+ T cells were lower in the patients. There was no correlation between clinical stage, sex, thymectomy, or pathology of thymus and the levels of CD5+ B cells, CD5- B cells, or CD19+ B cells. Patients treated with azathioprine had lower levels of CD5+ B cells than untreated patients and controls. Our results show that patients with myasthenia gravis have the same levels of CD5+ B cells as healthy individuals.     

Periductal lymphocytic infiltrates in salivary glands in myasthenia gravis patients lacking Sjögren''s syndrome.

In eight of eleven patients with clinical and serological evidence of myasthenia gravis (MG), immunohistological analysis of biopsies from labial salivary glands (LSG) showed focal periductal lymphocytic infiltrates, mainly composed of anti-Leu 3a+ T helper lymphocytes, a finding usually regarded as indicative for Sj?gren's syndrome (SS). None of the patients could however, according to functional criteria, be considered as having SS. This study thus indicates that lymphocytic infiltrates in LSG can be seen in MG, which has been thought of as an organspecific autoimmune disease with symptoms and signs confined to striated muscles.     

Circulating immune complexes induced by food proteins implicated in precocious myocardial infarction

BACKGROUND: Circulating immune complexes (CIC) are frequently found in postinfarction patients. The constituents of these CIC are mostly unknown. AIM: The objective of the current study was to assess whether CIC containing alimentary proteins and antibodies against these proteins are implicated in precocious myocardial infarction (MI). METHODS: Seventy-six survivors (67 men and 9 women, mean age 39 years) of a first MI before the age of 45 years were enrolled in this study. Two control groups were included. One group consisted of age-matched, randomly selected, population-based healthy individuals, 79 men and 11 women, without features of coronary heart disease. An additional control group was used only for the determination of serum antibodies against some of the alimentary proteins and consisted of 139 healthy blood donors, 95 men and 44 women, with a mean age of 42 years. Sucrose density gradient centrifugation, gel filtration and precipitation by polyethylene glycol were used for the isolation of CIC, and enzyme-linked immunosorbent assay (ELISA) was used to measure the immunoglobulin levels and specific antibodies against alimentary proteins in both sera and isolated CIC. Sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis and Western blotting were used to determine alimentary proteins in the CIC. RESULTS: Alimentary antigens/antibodies were present in immune complex form in seven out of 14 (50%) postinfarction patients who had persistent high concentrations of CIC, the latter constituting 18% of the entire group. Antibodies of the IgG isotype predominated. A rise in CIC, signs of activation of the classical complement pathway, and a rise in plasma concentrations of von Willebrand factor antigen (vWFAg) were evident within 1 week in four patients subjected to a 2-week elimination diet followed by a single challenge with cow's milk. CONCLUSION: This study suggests that dietary proteins occasionally give rise to persistent CIC, which may predispose to MI at a young age.     

Home deliveries: implications for adherence to nevirapine in a PMTCT programme in rural Malawi

Although nevirapine (NVP) is provided by prevention of mother-to-child-transmission (PMTCT) of HIV programmes to be taken at onset of labor independent of place of delivery, few studies have assessed adherence to NVP outside the hospital setting. This study aimed to follow women in a PMTCT programme up to delivery and to assess the adherence to the prophylaxis in rural Malawi. A total of 75 HIV-positive women were registered in the PMTCT at Malamulo SDA hospital between January and June 2005. Forty women (53%) delivered in the hospital and 35 (47%) did not. Of the 35 women who delivered at home, it was possible to trace 27 (77.2%). All women who delivered in the hospital took their NVP tablets and all their babies had NVP syrup except one baby who died soon after delivery. Of the 27 traced women who had not delivered in the hospital, 16 (59.3%) had access to NVP and had taken their tablets during labor. However, none of their babies was taken back to the health facility for NVP syrup. Traditional birth attendants might be crucial in efforts aiming to increase adherence to NVP among women and their babies.     

PTPN22 R620W promotes production of anti-AChR autoantibodies and IL-2 in myasthenia gravis

In order to investigate the potential involvement of PTPN22 R620W in the pathogenesis of myasthenia gravis (MG), we performed a case-control study including 409 Swedish MG patients and 1557 normal controls. The W620 variant was significantly overrepresented in patients (odds ratio, 1.52; 95% confidence interval, 1.21-1.90; p=0.00027). Incubation of patient (n=100) derived PBMC cells with the autoantigen, the acetylcholine receptor, resulted in a significantly higher number of cells producing anti-AChR antibodies and IL-2 in W620 carriers, suggesting that PTPN22 W620 may be a loss-of-function variant in MG.     

Higher glucose uptake in paralysed spastic leg

BACKGROUND: Insulin resistance and diabetes mellitus have been reported in the spinal cord injured (SCI). The group exhibits risk factors, as decreased physical activity, as well as episodes of stimulation of sympathetic nervous system below the level of lesion known to stimulate lipolysis, which in turn could induce insulin resistance. However, data are inconsistent, which might indicate the presence of protective mechanisms. OBJECTIVE: To investigate the glucose uptake in spastic paralysed SCI legs compared to able-bodied. To investigate regional differences between glucose handling in the arm and leg. STUDY DESIGN: Experimental controlled study. SETTINGS: Institution of Clinical Neuroscience and Physiology, Spinal Injures Unit, Sahlgrens University Hospital, Goteborg, Sweden. METHODS: Nine SCI subjects (2 C7, 7 T1-T4 ASIA A: 8, ASIA B: 1) were compared to 10 weight- and age-matched controls. Plasma flow in arm and leg was analysed by venous occlusion strain gauge plethysmography, and plasma derived from artery and veins in the arm and leg was analysed for glucose, insulin and lactate during fasting resting conditions. RESULTS: Glucose uptake was higher in SCI legs compared to controls. There was no difference in insulin uptake or lactate production. Plasma flow was higher in SCI legs compared to controls. Controls showed a higher glucose uptake and lactate production in arm than leg. CONCLUSIONS: Spasticity may counteract the risk of diabetes by inducing an insulin-independent glucose uptake. The regional difference in metabolism in able-bodied make it hazardous to do generalizations to whole body metabolism from arm or leg measurements.     

Microglia used as vehicles for both inducible thymidine kinase gene therapy and MRI contrast agents for glioma therapy

Microglia are phagocytic cells that are chemoattracted by brain tumors and can represent up to 70% of the tumor cell population. To get insight into gene therapy against glioma, we decided to take advantage of those microglia properties and to use those cells as vehicles to transport simultaneously a suicide gene (under the control of a heat-sensitive promoter) and contrast agents to localize them by magnetic resonance imaging before applying any therapeutic treatment. Thymidine kinase (TK) expression and its functionality after gancyclovir administration were investigated. After the heat shock (44 degrees C and 20 min), TK was expressed in 50% of the cells. However, after gancyclovir treatment, 90% of the cells died by apoptosis, showing an important bystander effect. Then, the cells were incubated with new lanthanide contrast agents to check both their potential toxicity and their MR properties. Results indicate that the nanoparticles did not induce any cell toxicity and yield a hypersignal on MR images at 4.7 T. These in vitro experiments indicate that microglia are good candidates as vectors in gene therapy against brain tumors. Finally, microglia containing gadolinium-grafted nanoparticles were injected in the close vicinity of C6 tumor, in a mouse. The hyperintensive signal obtained on in vivo images as well as its retention time show the potential of the novel contrast agents for cellular imaging.