Lymphocyte populations and their change during five-year glatiramer acetate treatment

Background

The goal of this study was to determine the characteristics that are affected in patients treated with glatiramer acetate (GA).

Chronic Peripheral Hyperinsulinemia in Type 1 Diabetic Patients After Successful Combined Pancreas-Kidney Transplantation Does Not Affect Ectopic Lipid Accumulation in Skeletal Muscle and Liver

OBJECTIVE

So far it is unclear whether chronic peripheral hyperinsulinemia per se might contribute to ectopic lipid accumulation and consequently insulin resistance. We investigated the effects of systemic instead of portal insulin release in type 1 diabetic patients after successful pancreas-kidney transplantation (PKT) with systemic venous drainage on the intracellular lipid content in liver and soleus muscle, endogenous glucose production (EGP), and insulin sensitivity.

RESEARCH DESIGN AND METHODS

In nine PKT patients and nine matching nondiabetic control subjects, intrahepatocellular lipids (IHCLs) and intramyocellular lipids (IMCLs) were measured using ¹H nuclear magnetic resonance spectroscopy. Fasting EGP was measured using d-[6,6-²H²]glucose tracer dilution. A 3-h 75-g oral glucose tolerance test (OGTT) allowed us to assess kinetics of glucose, free fatty acids, insulin, and C-peptide concentrations in plasma and to calculate the clamp-like index (CLIX) for insulin sensitivity and the hepatic insulin resistance (HIR) index.

RESULTS

The PKT patients displayed approximately twofold increased fasting insulin (20 ± 6 vs. 9 ± 3 μU/ml; P < 0.0002) compared with that in nondiabetic control subjects and ∼10% increased fasting glucose (P < 0.02) concentrations, but during the OGTT areas under the concentration curves of C-peptide and insulin were similar. IHCL (PKT, 2.9 ± 2.5%; nondiabetic control subjects, 4.4 ± 6.6%), IMCL (PKT, 1.0 ± 0.4%; nondiabetic control subjects, 1.0 ± 0.5%), CLIX (PKT, 8 ± 2; nondiabetic control subjects, 7 ± 3), HIR (PKT, 25.6 ± 13.2; nondiabetic control subjects, 35.6 ± 20 [mg · min⁻¹ · kg⁻¹] × [μU/ml]), and EGP (PKT, 1.6 ± 0.2; nondiabetic control subjects, 1.7 ± 0.2 mg · min⁻¹ · kg⁻¹) were comparable between PKT patients and nondiabetic control subjects. IHCL was negatively correlated with CLIX in all participants (r = −0.55; P < 0.04).

CONCLUSIONS

Despite fasting peripheral hyperinsulinemia because of systemic venous drainage, type 1 diabetic patients after PKT show similar IHCL, IMCL, insulin sensitivity, and fasting EGP in comparison with nondiabetic control subjects. These results suggest that systemic hyperinsulinemia per se does not cause ectopic lipid accumulation in liver and skeletal muscle.Insulin resistance has been linked to lipid accumulation in insulin-responsive tissues such as liver and skeletal muscle (1–3), but it is not yet clear if ectopic fat accumulation induces insulin resistance and consequently hyperinsulinemia or whether increased intracellular lipid content is rather the result of long-term hyperinsulinemia.Poorly controlled type 1 diabetic patients (4) as well as insulin-resistant type 2 diabetic subjects and the offspring of type 2 diabetic subjects displayed increased intracellular lipid content in skeletal muscle when compared with healthy individuals (1), whereas well-controlled type 1 diabetic patients exhibited an unchanged intramyocellular lipid content (5).Pancreatic transplantation in diabetic subjects with end-stage renal disease restores insulin secretion and glucose tolerance (6). Combined pancreas-kidney transplantation (PKT) with systemic venous drainage provides a human model that allows to study the long-term effects of systemic instead of portal insulin delivery on glucose metabolism and intracellular lipid content. It is worth noting that insulin replacement in diabetic patients is commonly administered subcutaneously into the systemic circulation and not through the portal vein (4,7). It is unclear whether this peripheral route of insulin delivery has clinically relevant consequences.We studied whether the systemic route of insulin appearance could affect intracellular lipid content in liver and skeletal muscle, as well as endogenous glucose production (EGP) in type 1 diabetes after successful pancreas transplantation.     

Advanced MR methods at ultra-high field (7 Tesla) for clinical musculoskeletal applications

Objectives

This article provides an overview of the initial clinical results of musculoskeletal studies performed at 7 Tesla, with special focus on sodium imaging, new techniques such as chemical exchange saturation transfer (CEST) and T2* imaging, and multinuclear MR spectroscopy.

Methods

Sodium imaging was clinically used at 7?T in the evaluation of patients after cartilage repair procedures because it enables the GAG content to be monitored over time. Sodium imaging and T2* mapping allow insights into the ultra-structural composition of the Achilles tendon and help detect early disease. Chemical exchange saturation transfer was, for the first time, successfully applied in the clinical set-up at 7?T in patients after cartilage repair surgery. The potential of phosphorus MR spectroscopy in muscle was demonstrated in a comparison study between 3 and 7?T, with higher spectral resolution and significantly shorter data acquisition times at 7?T.

Results

These initial clinical studies demonstrate the potential of ultra-high field MR at 7?T, with the advantage of significantly improved sensitivity for other nuclei, such as ²³Na (sodium) and ³¹P (phosphorus).

Conclusions

The application of non-proton imaging and spectroscopy provides new insights into normal and abnormal physiology of musculoskeletal tissues, particularly cartilage, tendons, and muscles.

Key Points

? 7?T magnetic resonance provides significantly improved sensitivity for ²³ Na and ³¹ P. ? Initial clinical studies have now demonstrated ultra-high field MR operating at 7?T. ? 7?T provides new insights into normal and abnormal physiology of musculoskeletal tissues.     

The direct costs of multiple sclerosis—study in the Czech Republic

Background

Multiple sclerosis (MS) is a progressive autoimmune disease of the central nervous system that is often disabling and for which there is currently no cure, though disease-modifying treatment is now available. The aim of this study is to describe the current values of the direct costs of multiple sclerosis (MS) in the Czech Republic.

Methods

Attention is focused on direct medical costs. The costs were monitored in the Czech Republic among 5673 patients in the period between 2011 and 2015. These costs included complex, special and targeted visits at the neurologist, blood collection and the costs of hospitalisation. The results refer to the diagnoses according to the International Statistical Classification of Diseases and Related Health Problems. The attention is focused on MS G35 (NS; brain stem; spinal cord; disseminated; generalised).

Results

The average total direct costs per patient per year are 4838.1 €. Not every patient has to be hospitalised during the year, and not every patient has prescribed medication. According to the above data, 12% of patients are hospitalised and 55% of patients are prescribed medication. The minimum average cost per patient without medication and hospitalisation is 54.1 €.

Conclusion

Cost evaluation across countries is difficult due to the different evidence. If only selected direct costs considered in this study are compared, the absolute economics burden increases over time. The only statistically significant difference in the average price and the time spent is between 2012 and 2013, where the correlation value is 0.597.

     

Stellenwert der multiparametrischen Magnetresonanztomographie beim Prostatakarzinom

Prostate cancer is biologically and clinically a heterogeneous disease which makes imaging evaluation challenging. Magnetic resonance imaging (MRI) has considerable potential to improve prostate cancer detection and characterization. Until recently morphologic MRI has not been routinely incorporated into clinical care because of its limitation to detect, localize and characterize prostate cancer. Performing prostate gland MRI using functional techniques has the potential to provide unique information regarding tumor behavior, including treatment response. In order for multiparametric MRI data to have an impact on patient management, the collected data need to be relayed to clinicians in a standardized way for image construction, analysis and interpretation. This will ensure that patients are treated effectively and in the most appropriate way. Scoring systems similar to those employed successfully for breast imaging need to be developed.