Prediabetes and structural brain abnormalities: Evidence from observational studies

Type 2 diabetes mellitus has been linked to structural brain abnormalities, but evidence of the association among prediabetes and structural brain abnormalities has not been systematically evaluated. Comprehensive searching strategies and relevant studies were systematically retrieved from PubMed, Embase, Medline and web of science. Twelve articles were included overall. Stratified analyses and regression analyses were performed. A total of 104 468 individuals were included. The risk of infarct was associated with continuous glycosylated haemoglobin (HbA_1c) [adjusted odds ratio (OR) 1.19 (95% confidence interval [CI]: 1.05‐1.34)], or prediabetes [adjusted OR 1.13 (95% CI: 1.00‐1.27)]. The corresponding ORs associated with white matter hyperintensities were 1.08 (95%CI: 1.04‐1.13) for prediabetes, and 1.10 (95%CI: 1.08‐1.12) for HbA_1c. The association was significant between the decreased risk of brain volume with continuous HbA_1c (the combined OR 0.92, 95% CI: 0.87‐0.98). Grey matter volume and white matter volume were inversely associated with prediabetes [weighted mean deviation (WMD), ?9.65 (95%CI: ?15.25 to ?4.04) vs WMD, ?9.25 (95%CI: ?15.03 to ?3.47)]. There were no significant association among cerebral microbleeds, hippocampal volume, continuous total brain volume, and prediabetes. Our findings demonstrated that (a) both prediabetes and continuous HbA_1c were significantly associated with increasing risk of infarct or white matter hyperintensities; (b) continuous HbA_1c was associated with a decreased risk of brain volume; (c) prediabetes was inversely associated with grey matter volume and white matter volume. To confirm these findings, further studies on early diabetes onset and structural brain abnormalities are needed.     

Transgenerational programming of maternal behaviour by prenatal stress

Peripartum events hold the potential to have dramatic effects in the programming of physiology and behaviour of offspring and possibly subsequent generations. Here we have characterized transgenerational changes in rat maternal behaviour as a function of gestational and prenatal stress. Pregnant dams of the parental generation were exposed to stress from days 12-18 (F0-S). Their daughters and grand-daughters were either stressed (F1-SS, F2-SSS) or non-stressed (F1-SN, F2-SNN). Maternal antepartum behaviours were analyzed at a time when pregnant dams usually show a high frequency of tail chasing behaviours. F1-SS, F2-SNN and F2-SSS groups showed a significant reduction in tail chasing behaviours when compared with controls. The effects of multigenerational stress (SSS) slightly exceeded those of transgenerational stress (SNN) and resulted in absence of tail chasing behaviour. These findings suggest that antepartum maternal behaviour in rats is programmed by transgenerational inheritance of stress responses. Thus, altered antepartum maternal behaviour may serve as an indicator of an activated stress response during gestation.     

Diagnostic value of salivary cortisol in Cushing's syndrome (CS)

Objective The diagnosis of Cushing's syndrome (CS) remains a challenge in clinical endocrinology. The aim of this study was to determine the reproducibility and diagnostic value of late‐night salivary cortisol (SAF₂₃) for CS and its utility along the follow‐up of treated patients. In addition, using the same radioimmunoassay reactives, the cut‐off values for saliva and serum cortisol, assessed synchronically after the overnight 1 mg dexamethasone suppression test (DST), were defined. Design Twenty‐one patients with confirmed CS and 121 volunteers were studied. All the subjects collected 24‐h urine for cortisol (UFC). On the same day whole saliva was obtained from the subjects at 23 h for SAF₂₃. The intraclass coefficient of correlation (ICC) of SAF₂₃ was estimated in 47 subjects (21 CS and 26 C). At 8 h, after DST, simultaneous saliva and serum samples for cortisol (SAF_dex and F_dex, respectively) were obtained in 51 subjects (17 CS and 34 C). After specific therapy, 18 patients with CS were followed with SAF₂₃ measurements. SAF and F were expressed as nm . Results The intraclass coefficient of correlation of SAF₂₃ was 0·89 in CS and 0·83 in C. SAF₂₃ > 3·8 nm showed a sensitivity and specificity of 100% and 97·5%, respectively, for diagnosing CS. SAF₂₃ correlated positively with UFC (r = 0·685; P = 0·0001). After DST, SAF_dex significantly correlated with F_dex (r = 0·61, P < 0·0001). A cut‐off value of SAF_dex > 2·0 nm and F_dex > 50·0 nm detected CS with 100% sensitivity and specificity. After successful surgical therapy, 13 patients with CS had SAF₂₃ levels < 3·8 nm (1·4 ± 0·8 nm ). Conclusions SAF₂₃ and SAF_dex seem to be good screening tools based on their noninvasive nature, remarkable reproducibility and diagnostic performances.     

Additional cardiac investigation prior to the introduction of the CAD-RADS classification in coronary computed tomography angiography reports

Introduction

The CAD-RADS^TM classification was recently introduced in an attempt to standardize coronary computed tomography angiography (CCTA) reports and to provide recommendations for further management. The aim of this study was to assess how additional cardiac investigations were being ordered before the introduction of the CAD-RADS classification in a tertiary hospital's CCTA reports.

Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies.

We have previously shown that leukemia-specific cytotoxic T cells (CTL) can be generated from the bone marrow of most patients with B-cell precursor acute leukemias. If these antileukemia CTL are to be used for adoptive immunotherapy, they must have the capability to circulate, migrate through endothelium, home to the bone marrow, and, most importantly, lyse the leukemic cells in a leukemia-permissive bone marrow microenvironment. We demonstrate here that such antileukemia T-cell lines are overwhelmingly CD8(+) and exhibit an activated phenotype. Using a transendothelial chemotaxis assay with human endothelial cells, we observed that these T cells can be recruited and transmigrate through vascular and bone marrow endothelium and that these transmigrated cells preserve their capacity to lyse leukemic cells. Additionally, these antileukemia T-cell lines are capable of adhering to autologous stromal cell layers. Finally, autologous antileukemia CTL specifically lyse leukemic cells even in the presence of autologous marrow stroma. Importantly, these antileukemia T-cell lines do not lyse autologous stromal cells. Thus, the capacity to generate anti-leukemia-specific T-cell lines coupled with the present findings that such cells can migrate, adhere, and function in the presence of the marrow microenvironment enable the development of clinical studies of adoptive transfer of antileukemia CTL for the treatment of ALL.     

First human experience with endoscopically delivered and retrieved duodenal-jejunal bypass sleeve

BACKGROUND: We report the first human experience with an endoscopic duodenal-jejunal bypass sleeve (DJBS) in a community hospital. METHODS: The DJBS is a 60-cm sleeve anchored in the duodenum to create a duodenal-jejunal bypass. In a 12-patient prospective, open-label, single-center, 12-week study, the device was endoscopically implanted, left in situ, and retrieved. The study included 5 men and 7 women, with a mean body mass index of 43 kg/m(2). Of the 12 patients, 4 had type 2 diabetes. The primary endpoints were the incidence and severity of adverse events. The secondary outcomes included the percentage of excess weight loss and changes in co-morbid status. RESULTS: The DJBS was endoscopically delivered and retrieved in all patients (mean implant/explant time of 26.6 and 43.3 min, respectively). Of the 12 patients, 10 were able to maintain the device for 12 weeks and 2 underwent explantation after 9 days secondary to poor device placement. Several self-limited adverse events were possibly or definitely related to the device, including 6 episodes of abdominal pain, 18 of nausea, and 16 of vomiting, mainly within 2 weeks of implantation. Two partial pharyngeal tears occurred during explantation. Implant site inflammation was encountered in all patients. No device-related event was considered severe. The average percentage of excess weight loss for the 10 patients with the device in place for 12 weeks was 23.6%, with all patients achieving at least 10% excess weight loss. All 4 diabetic patients had normal fasting plasma glucose levels without hypoglycemic medication for the entire 12 weeks. Of these 4 patients, 3 had decreased hemoglobin A(1c) of > or =.5% by week 12. CONCLUSION: The DJBS can be safely delivered and removed endoscopically and left in situ for 12 weeks. The device had a favorable safety and encouraging efficacy profile. Randomized prospective trials are warranted.     

Penicillin-resistant pneumococcus and risk of treatment failure in pneumonia.

OBJECTIVE: To determine whether the presence of in vitro penicillin-resistant Streptococcus pneumoniae increases the risk of clinical failure in children hospitalised with severe pneumonia and treated with penicillin/ampicillin. DESIGN: Multicentre, prospective, observational study. SETTING: 12 tertiary-care centres in three countries in Latin America. PATIENTS: 240 children aged 3-59 months, hospitalised with severe pneumonia and known in vitro susceptibility of S pneumoniae. INTERVENTION: Patients were treated with intravenous penicillin/ampicillin after collection of blood and, when possible, pleural fluid for culture. The minimal inhibitory concentration (MIC) test was used to determine penicillin susceptibility of the pneumococcal strains isolated. Children were continuously monitored until discharge. MAIN OUTCOME MEASURES: The primary outcome was treatment failure (using clinical criteria). RESULTS: Overall treatment failure was 21%. After allowing for different potential confounders, there was no evidence of association between treatment failure and in vitro resistance of S pneumoniae to penicillin according to the Clinical Laboratory Standards Institute (CLSI)/National Committee for Clinical Laboratory Standards (NCCLS) interpretative standards ((adj)RR = 1.03; 95%CI: 0.49-1.90 for resistant S pneumoniae). CONCLUSIONS: Intravenous penicillin/ampicillin remains the drug of choice for treating penicillin-resistant pneumococcal pneumonia in areas where the MIC does not exceed 2 microg/ml.     

Frequency of social phobia and psychometric properties of the Liebowitz social anxiety scale in Parkinson's disease

There are few studies about social anxiety disorder in Parkinson's disease (PD). The objective of this study was to assess its frequency and to explore the psychometric properties of the Liebowitz social anxiety scale (LSAS) in PD. Ninety patients with PD underwent neurologic and psychiatric examination. Psychiatric examination was composed by a structured clinical interview (MINI‐Plus) followed by the application of the LSAS, the Hamilton depression rating scale (Ham‐D), and the Hamilton anxiety rating scale (Ham‐A). Neurologic examination included the MMSE, the UPDRS, the Hoehn‐Yahr Scale, and the Schwab‐England scale of activities of daily living. Social phobia was diagnosed in 50% of PD patients. The disorder was not associated with any sociodemographic or neurological feature, but was associated to major depression (P = 0.023), generalized anxiety disorder (P = 0.023), and obsessive‐compulsive disorder (P = 0.013). The score of LSAS correlated positively with the scores of Ham‐D and Ham‐A (P < 0.001 for both). A ROC curve analysis of the LSAS suggested that a cutoff score in 41/42 provided the best balance between sensitivity and specificity. This disorder seems to be more common and not just restricted to performance as previously thought. © 2008 Movement Disorder Society