Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART

Recent evidence indicates that regulatory T cells (T(regs)) play an important role in HIV infection. However, although the gastrointestinal mucosa is a key compartment in HIV disease, no data on mucosal T(regs) in HIV infection are available. In this study, we compared the frequency of T(regs) in duodenal mucosa and peripheral blood (PB) of 13 treatment-naive and 13 suppressively treated HIV-infected patients with that of 6 patients with norovirus infection and 12 healthy controls. T(regs) were quantified by immunohistochemistry (CD3/FOXP3) and further characterized (CD25, CTLA-4, GITR) by immunohistochemistry, immunofluorescence, and fluorescence-activated cell sorting (FACS). Both the frequency and the absolute count of mucosal T(regs) were highly increased in untreated HIV patients but were normal in treated HIV patients. In contrast, in peripheral blood of HIV patients, the absolute number of T(regs) was not increased, and their frequency was only slightly elevated. In norovirus infection, frequency of mucosal T(regs) in the CD4+ T-cell subset was not elevated. The high increase in count and frequency of mucosal T(regs) seems to be a characteristic feature of untreated HIV infection, suggesting a significant contribution of T(regs) to the pathogenesis of HIV disease. Their role may be 2-edged: attenuating HIV-induced immune hyperactivation while suppressing the immune response to HIV and mucosal pathogens.     

Can Prognostic Factors Be Used to Direct Therapy in Chronic Lymphocytic Leukemia?

Chronic lymphocytic leukemia (CLL) shows a heterogeneous clinical course, which can be explained in part by prognostic factors. Most patients do not need treatment at the time of first diagnosis. The identification of prognostic factors is of major interest if strategies can be devised to treat patients according to their individual risk profile or biological subgroup. Currently, in spite of a wealth of prognostic factors, individualized treatment approaches in different genetic or risk groups are the exemption in CLL. This review summarizes the most important prognostic and predictive factors in CLL, with particular emphasis on factors affecting treatment decisions in clinical trials and routine practice.     

Hypothalamic dysfunction and neuroendocrine and metabolic alterations in Huntington's disease: clinical consequences and therapeutic implications

Huntington's disease (HD) is a hereditary neurodegenerative disorder characterized by cognitive, psychiatric, behavioural and motor disturbances. Although the course of HD is also frequently complicated by unintended weight loss, sleep disturbances and autonomic nervous system dysfunction, the aetiology of these signs and symptoms remains largely unknown. In recent years, many novel findings from both animal and human studies have emerged that indicate considerable hypothalamic, endocrine and metabolic alterations in HD. However, a comprehensive overview of these findings is lacking and their precise clinical significance is far from clear. Therefore, in this review we attempt to put these recent developments in the field into perspective by integrating them with previous findings in a comprehensible manner, and by discussing their clinical relevance, with a special focus on body weight, sleep and autonomic functions in HD, which will also allow for the identification of future lines of research in this area.     

Gut-brain axis: regulation of glucose metabolism

Obesity and type II diabetes mellitus have reached epidemic proportions. From this perspective, knowledge about the regulation of satiety and food intake is more important than ever. The gut releases several peptides upon feeding, which affect hypothalamic pathways involved in the regulation of satiety and metabolism. Within the hypothalamus, there are complex interactions between many nuclei of which the arcuate nucleus is considered as one of the most important hypothalamic centres that regulates food intake. The neuropeptides, which are present in the hypothalamus and are involved in regulating food intake, also play a key role in regulating glucose metabolism and energy expenditure. In synchrony with the effects of those neuropeptides, gastrointestinal hormones also affect glucose metabolism and energy expenditure. In this review, the effects of the gastrointestinal hormones ghrelin, cholecystokinin, peptide YY, glucagon-like peptide, oxyntomodulin and gastric inhibitory polypeptide on glucose and energy metabolism are reviewed. These gut hormones affect glucose metabolism at different levels: by altering food intake and body weight, and thereby insulin sensitivity; by affecting gastric delay and gut motility, and thereby meal-related fluctuations in glucose levels; by affecting insulin secretion, and thereby plasma glucose levels, and by affecting tissue specific insulin sensitivity of glucose metabolism. These observations point to the notion of a major role of the gut-brain axis in the integrative physiology of whole body fuel metabolism.     

Percutaneous Computed Tomography–guided High-Dose-Rate Brachytherapy Ablation of Breast Cancer Liver Metastases: Initial Experience with 80 Lesions

PurposeTo analyze initial experience with computed tomography–guided high-dose-rate brachytherapy (CT-HDRBT) ablation of breast cancer liver metastases (BCLM).Materials and MethodsBetween January 2008 and December 2010, 37 consecutive women with 80 liver metastases were treated with CT-HDRBT in 56 sessions. Mean age was 58.6 years (range, 34–83 y). Treatment was performed by CT-guided applicator placement and high-dose-rate brachytherapy with an iridium-192 source. The mean radiation dose was 18.57 Gy (standard deviation 2.27). Tumor response was evaluated by gadoxetic acid–enhanced liver magnetic resonance (MR) imaging performed before treatment, 6 weeks after treatment, and every 3 months thereafter.ResultsTwo patients were lost to follow-up; the remaining 35 patients were available for MR imaging evaluation for a mean follow-up time of 11.6 months (range 3–32 mo). Mean tumor diameter was 25.5 mm (range 8–74 mm). Two (2.6%) local recurrences were observed after local tumor control for 10 months and 12 months. Both local progressions were successfully retreated. Distant tumor progression (new metastases or enlargement of nontreated metastases) occurred during the follow-up period in 11 (31.4%) patients. Seven (20%) patients died during the follow-up period. Overall survival ranged from 3–39 months (median 18 months).ConclusionsCT-HDRBT is a safe and effective ablative therapy, providing a high rate of local tumor control in patients with BCLM.