Estrogen blunts neuroendocrine and metabolic responses to hypoglycemia

This study tested the hypothesis that estrogen is the mechanism responsible for the sexual dimorphism present in the neuroendocrine and metabolic responses to hypoglycemia. Postmenopausal women receiving (E2; n = 8) or not receiving (NO E2; n = 9) estrogen replacement were compared with age- and BMI-matched male subjects (n = 8) during a single-step 2-h hyperinsulinemic-hypoglycemic clamp. Plasma insulin (599 +/- 28 pmol/l) and glucose (2.9 +/- 0.03 mmol/l) levels were similar among all groups during the glucose clamp. In response to hypoglycemia, epinephrine (2.8 +/- 0.6 vs. 5.8 +/- 0.8 and 4.4 +/- 0.5 nmol/l), glucagon (57 +/- 8 vs. 77 +/- 8 and 126 +/- 18 ng/l), and endogenous glucose production (2 +/- 2 vs. 10 +/- 2 and 6 +/- 3 micro mol x kg(-1) x min(-1)) were significantly lower in E2 vs. both NO E2 and male subjects (P < 0.05). These reduced counterregulatory responses resulted in significantly greater glucose infusion rates (16 +/- 2 vs. 6 +/- 2 and 6 +/- 3 micro mol x kg(-1) x min(-1); P < 0.01) in E2 vs. both NO E2 and male subjects. Pancreatic polypeptide was significantly lower (P < 0.05) in both the E2 and NO E2 groups compared with the male subjects (136 +/- 20 and 136 +/- 23 vs. 194 +/- 16 pmol/l). Last, glycerol (36 +/- 3 vs. 47 +/- 5 micro mol/l; P < 0.05), lactate (1.4 +/- 0.1 vs. 1.8 +/- 0.2 mmol/l; P < 0.05), and muscle sympathetic nerve activity (19 +/- 4 to 27 +/- 4 vs. 27 +/- 5 to 42 +/- 6 bursts/min; P < 0.05) responses to hypoglycemia were all significantly lower in E2 vs. NO E2 subjects. We conclude that estrogen appears to play a major role in the sexual dimorphism present in counterregulatory responses to hypoglycemia in healthy humans.     

Segmentation of subtraction images for the measurement of lesion change in multiple sclerosis

BACKGROUND AND PURPOSE: Lesion volume change (LVC) assessment is essential in monitoring MS progression. LVC is usually measured by independently segmenting serial MR imaging examinations. Subtraction imaging has been proposed for improved visualization and characterization of lesion change. We compare segmentation of subtraction images (SSEG) with serial single time-point conventional segmentation (CSEG) by assessing the LVC relationship to brain atrophy and disease duration, as well as scan-rescan reproducibility and annual rates of lesion accrual.MATERIALS AND METHODS: Pairs of scans were acquired 1.5 to 4.7 years apart in 21 patients with multiple sclerosis (MS). Scan-rescan MR images were acquired within 30 minutes in 10 patients with MS. LVC was measured with CSEG and SSEG after coregistration and normalization. Coefficient of variation (COV) and Bland-Altman analyses estimated method reproducibility. Spearman rank correlations probed associations between LVC and other measures.RESULTS: Atrophy rate and net LVC were associated for SSEG (R = −0.446; P < .05) but not when using CSEG (R = −0.180; P = .421). Disease duration did not show an association with net lesion volume change per year measured by CSEG (R = −0.360; P = .11) but showed an inverse correlation with SSEG-derived measurements (R = −0.508; P < .05). Scan-rescan COV was lower for SSEG (0.98% ± 1.55%) than for CSEG (8.64% ± 9.91%).CONCLUSION: SSEG unveiled a relationship between T2 LVC and concomitant brain atrophy and demonstrated significantly higher measurement reproducibility. SSEG, a promising tool providing detailed analysis of subtle alterations in lesion size and intensity, may provide critical outcome measures for clinical trials of novel treatments, and may provide further insight into progression patterns in MS.

MR imaging has evolved as a core paraclinical tool for the diagnosis, longitudinal monitoring, and scientific investigation of multiple sclerosis (MS). Subsequent to documenting disease effects at 1 time point, assessing longitudinal change has evolved as the dominant role of MR imaging. In particular, quantification of MR imaging lesion burden has served an important role in the evaluation of MS progression and treatment effects.^1–5 As the expected average annual change in T2 hyperintense lesion volume has been reported to be only 5%–10%,⁶ the sensitivity of quantitative analysis of lesion burden change is paramount. Established methods for evaluating the change in T2 lesions include manual counting of total, new, enlarging, and resolving lesions⁷ and quantitative segmentation of total lesion load at each time point.^8–17Direct segmentation of lesion change based on subtraction of coregistered serial MR images has not yet been extensively studied. This approach promises to be a more robust and sensitive alternative for measuring disease progression on serial MR imaging scans, because it focuses quantification efforts on the subset of lesions showing change, which frequently represent a very small fraction of all lesions.Subtraction imaging, which cancels stable disease, provides enhanced sensitivity to characterize lesions by separately identifying new, enlarging, and resolving MS lesions.^7,18 The segmentation of subtraction images quantifies the new, enlarging, and resolving MS lesions seen on subtraction imaging.In this article, we assessed the sensitivity of 2 image analysis strategies: conventional segmentation followed by the determination of numeric differences between total lesion volumes at each time point (CSEG) versus the segmentation of subtraction images (SSEG). We compared the average yearly change in MS lesion burden using each of these 2 methods and determined measurement precision. By way of external validation, we related the 2 change measures with changes in brain parenchymal fraction (BPF) and disease duration.     

Use of risk stratification to target therapies in patients with recent onset arthritis; design of a prospective randomized multicenter controlled trial

Background  

Early and intensive treatment is important to inducing remission and preventing joint damage in patients with rheumatoid arthritis. While intensive combination therapy (Disease Modifying Anti-rheumatic Drugs and/or biologicals) is the most effective, rheumatologists in daily clinical practice prefer to start with monotherapy methotrexate and bridging corticosteroids. Intensive treatment should be started as soon as the first symptoms manifest, but at this early stage, ACR criteria may not be fulfilled, and there is a danger of over-treatment. We will therefore determine which induction therapy is most effective in the very early stage of persistent arthritis. To overcome over-treatment and under-treatment, the intensity of induction therapy will be based on a prediction model that predicts patients' propensity for persistent arthritis.     

恶性肿瘤淋巴管生成与转移的研究进展

淋巴道转移是肿瘤转移的重要途径,也是判断预后的重要依据. 随着淋巴管生成因子及许多淋巴管特异性标记物的发现,肿瘤新生淋巴管调控与淋巴道转移机制研究得以深入开展. 大量的研究发现,恶性肿瘤和瘤周组织内存在新生的淋巴管,新生的淋巴管密度和淋巴管标记物的表达强度均与淋巴结转移密切相关. 这为揭示恶性肿瘤淋巴道转移机制和开发淋巴管靶向治疗提供了重要的研究途径. 现就近年来肿瘤淋巴管生成与转移的研究进展作一综述.     

下消化道出血221例分析

0　引言　下消化道出血是消化科的常见病 ,是指十二指肠空肠移行部 ,屈氏韧带以下的小肠和大肠疾病引起的肠道出血 .有人认为一般不包括痔和肛裂出血 [1 ] .临床最常见为慢性出血 ,但有时出血量大危及生命 ,需要做紧急处理 ,现将我院1992 - 0 1/ 1999- 0 8门诊及病房收治的 2 2 1例下消化道出血进行分析 ,报告如下 :1　临床资料　男 12 0例 ,女 10 1例 ,年龄 14～ 72 (平均 42 )岁 ,病程 16 h～ 10 a.患者分别以脓血便、暗红色血便、鲜血便或果酱色血便为主诉前来就诊 ,其中有休克症状的大出血者6例 .血 Hb<110 g·L- 1 40例 ,<80 g·L- 1…     

Microtubule reassembly in surface-activated platelets

It is generally accepted that a circumferential microtubule supports the discoid shape of resting platelets. The fate of the many-coiled polymer following platelet activation, however, has been a subject of considerable debate. Morphological investigations have suggested that the circumferential coils are constricted into tight rings around centrally concentrated organelles during platelet shape change. Biochemical studies employing colchicine-binding assays, on the other hand, have indicated that the bundle of microtubules dissolves almost completely within seconds after activation and reassembles in a new location one to four minutes later. The present study has accepted the latter hypothesis in order to examine the second part of the disassembly-reassembly theory proposed in biochemical studies. Platelets exposed to low temperatures sufficient to remove all microtubules were placed on glass slides and microscope grids to cause surface activation during rewarming. The combined stimuli of rewarming and surface activation might have been expected to cause more rapid assembly than warming alone or activation alone. This was not the case. Reassembly of microtubules during rewarming and simultaneous surface activation was not accelerated. In contrast to the constriction of microtubule rings observed during activation in control platelets, the diameters of coils that developed in chilled platelets one to two hours after rewarming and surface activation were twice those of control cells.     

The lupus anticoagulant in systemic lupus erythematosus and systemic sclerosis

The lupus anticoagulant is an acquired IgG or IgM antibody directed against specific phospholipids involved in the formation of prothrombin activators. It is identified by coagulation tests. The partial thromboplastin time and kaolin clotting time are prolonged and these abnormalities cannot be corrected by the addition of normal plasma, as in simple clotting factor deficiency. The thrombin time is normal.
Five out of 36 unselected patients with systemic lupus erythematosus (SLE) showed the presence of lupus anticoagulant (14%). The duration of SLE was from 2 to 38 years. Three of the five patients gave a history of thrombosis. The only male patient suffered from myocardial infarction and venous thromboses in his twenties and is an example of a group of young males with major thrombotic episodes. One patient had a Coombs-positive haemolytic anaemia. Thrombocytopenia is sometimes associated with the lupus anticoagulant but was not found in the present series. Anticardiolipin antibodies were not measured, but none of the patients had false-positive serology.
The lupus anticoagulant is a useful marker for those patients with SLE at risk for thrombosis.
The lupus anticoagulant was not found in 24 unselected patients with systemic sclerosis and is therefore not a factor in the pathogenesis of the vascular phenomena in this disease.     

The incidence and prognosis of Brugada electrocardiographic pattern in the Manitoba Follow-Up Study

BACKGROUND: There is a paucity of long-term follow-up data on individuals with asymptomatic Brugada electrocardiographic (ECG) pattern. OBJECTIVES: To investigate the incidence and prognosis of spontaneous Brugada ECG pattern in a prospective cohort. METHODS: The Manitoba Follow-up Study is Canada's longest-running study of cardiovascular disease. Since 1948, a cohort of 3983 healthy aircrew recruits has been followed with routine medical examination, including ECG. Over a 55-year follow-up period, clinical and ECG assessments were performed every three to five years, with yearly contact to monitor vital status. The mean age of the cohort at entry and the average age of the 1375 survivors in 2003 were 31 and 83 years of age, respectively. Brugada ECG pattern was defined as ST-segment elevation in at least one of leads V1 to V3 with a J wave amplitude of at least 2 mm, negative T waves, generally coved ST-T configuration, in the absence of alternative explanations. Serial ECGs of 273 subjects (6.9% of the cohort) with complete right bundle branch block at any time during follow-up were reviewed. Follow-up records pertaining to clinical course were also reviewed. RESULTS: All ECGs (in total 5665) from this cohort were reviewed. Four men had intermittent Brugada ECG pattern (lifetime incidence one per 1000): three men (all 80 years of age or older) were well on last follow-up and one had died of Alzheimer's disease. None of these men had syncope or ventricular arrhythmias documented during follow-up. CONCLUSIONS: The longevity of asymptomatic individuals in this cohort was not affected by spontaneous Brugada ECG pattern.     

Change in Alcohol Use Based on Self-Report and a Quantitative Biomarker,Phosphatidylethanol, in People With HIV

AIDS and Behavior - The timeline followback (TLFB) takes more resources to collect than the Alcohol Use Disorder Identification Test (AUDIT-C). We assessed agreement of TLFB and AUDIT-C with the...