Allochronic taxa as an alternative model to explain circumantarctic disjunctions

Most biogeographical studies propose that southern temperate faunal disjunctions are either the result of vicariance of taxa originated in Gondwana or the result of transoceanic dispersal of taxa originated after the breakup of Gondwana. The aim of this paper is to show that this is a false dichotomy. Antarctica retained a mild climate until mid-Cenozoic and had lasting connections, notably with southern South America and Australia. Both taxa originally Gondwanan and taxa secondarily on Gondwanan areas were subjected to tectonic-induced vicariance, and there is no need to invoke ad hoc transoceanic dispersal, even for post-Gondwanan taxa. These different elements with circumantarctic distributions are here called `allochronic taxa` - taxa presently occupying the same area, but whose presence in that area does not belong to the same time period. This model allows accommodation of conflicting sources of evidence now available for many groups with circumantarctic distributions. The fact that the species from both layers are mixed up in the current biodiversity implies the need to use additional sources of evidence - such as biogeographical, palaeontological, geological and molecular - to discriminate which are the original Gondwanan and which are post-Gondwanan elements in austral landmasses.

ICRAM (the International Campaign to Revitalise Academic Medicine): Agenda setting

Following die launch by the BMJ and others of the campaign to promote academic medicine, a working party of 20 medical academics from all over the world was convened to develop a plan of action.

Prostatic Artery Embolization as a Primary Treatment for Benign Prostatic Hyperplasia: Preliminary Results in Two Patients

Symptomatic benign prostatic hyperplasia (BPH) typically occurs in the sixth and seventh decades, and the most frequent obstructive urinary symptoms are hesitancy, decreased urinary stream, sensation of incomplete emptying, nocturia, frequency, and urgency. Various medications, specifically 5-alpha-reductase inhibitors and selective alpha-blockers, can decrease the severity of the symptoms secondary to BPH, but prostatectomy is still considered to be the traditional method of management. We report the preliminary results for two patients with acute urinary retention due to BPH, successfully treated by prostate artery embolization (PAE). The patients were investigated using the International Prostate Symptom Score, by digital rectal examination, urodynamic testing, prostate biopsy, transrectal ultrasound (US), and magnetic resonance imaging (MRI). Uroflowmetry and postvoid residual urine volume complemented the investigation at 30, 90, and 180 days after PAE. The procedure was performed under local anesthesia; embolization of the prostate arteries was performed with a microcatheter and 300- to 500-mu m microspheres using complete stasis as the end point. One patient was subjected to bilateral PAE and the other to unilateral PAE; they urinated spontaneously after removal of the urethral catheter, 15 and 10 days after the procedure, respectively. At 6-month follow-up, US and MRI revealed a prostate reduction of 39.7% and 47.8%, respectively, for the bilateral PAE and 25.5 and 27.8%, respectively, for the patient submitted to unilateral PAE. The early results, at 6-month follow-up, for the two patients with BPH show a promising potential alternative for treatment with PAE.

Exploring the use of Viagra in place of animal and plant potency products in traditional Chinese medicine

Recently, conservationists have debated whether consumers of animal and plant potency products used to treat erectile dysfunction (ED) in traditional Chinese medicine (TCM) might be switching to Viagra, consequently consuming fewer of these animals and plants. To address this question, a survey examined the medical decisions of male consumers of TCM in Hong Kong who were over the age of 50. As predicted, these consumers reported selectively switching to Western medicines to treat ED, but not to treat other health ailments. These findings provide support for the possibility that Viagra may have conservation benefits for certain species.

Use of AST platelet ratio index (APRI Score) as an alternative to liver biopsy for treatment indication in chronic hepatitis C

Chronic hepatitis C (CHC) is one of the most important causes of chronic liver disease in the world, potentially resulting in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. Liver biopsy is currently performed before therapy indication. Although, it is the golden standard there are many reasons to avoid or delay the procedure. APRI Score is an easy, low cost and practice alternative method which was described as an alternative for assessing structural changes in chronic hepatitis C (CHC). The rationale of this study was to observe the accuracy of APRI Score in comparison to liver biopsy in 400 patients divided into two groups of 200 carriers (Validation and Experimental groups respectively) selected at random or according to liver fibrosis staging (METAVIR). The ROC curves showed a concordance among these two methods of 92% and 88.5% when 1.05 was the cut off (F3 and F4), and 87% and 83%, on 0.75 cut offs (F2-F4). The discordance in advanced fibrosis staging (F3 and F4) was only 16 (8%) and 22 (11%) out of 200 patients in the experimental and validation groups, respectively. In 26 (13%) out of 200 patients in the experimental group and 34 (17%) out of 200 patients in the validation group, there was discordance between APRI Score and liver biopsy in moderate and advanced fibrosis (F2-F4). In conclusion APRI is a serological marker that has satisfactory sensitivity and specificity together with a high predictive value and it can be useful either in the absence of a biopsy or to reduce the frequency with which biopsies need to be carried out to monitor the evolution of chronic hepatitis C and the right moment for treatment indication.

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. Of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173. Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50). Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis. Funding Bristol-Myers Squibb.

DEVELOPING THE INTERNATIONAL SOCIETY OF PHYSICAL AND REHABILITATION MEDICINE (ISPRM): FOLLOWING THROUGH

In 2008 the International Society of Physical and Rehabilitation Medicine (ISPRM) started an initiative to systematically develop its capacity and its internal and external policy agenda. This paper sums up achievements that have been made with this ISPRM initiative as well as pending issues and strategies to address them. The paper treats the following: ISPRM`s policy agenda in collaboration with the World Health Organization (WHO), research capacity in functioning and rehabilitation, ISPRM world conferences, relationships with regional societies of Physical and Rehabilitation Medicine (PRM), and ISPRM`s membership and governance structure.

Book review: Humane medicine by Miles Little

No abstract

Ten-Year Follow-Up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) A Randomized Controlled Clinical Trial of 3 Therapeutic Strategies for Multivessel Coronary Artery Disease

Background-This study compared the 10-year follow-up of percutaneous coronary intervention (PCI), coronary artery surgery (CABG), and medical treatment (MT) in patients with multivessel coronary artery disease, stable angina, and preserved ventricular function. Methods and Results-The primary end points were overall mortality, Q-wave myocardial infarction, or refractory angina that required revascularization. All data were analyzed according to the intention-to-treat principle. At a single institution, 611 patients were randomly assigned to CABG (n = 203), PCI (n = 205), or MT (n = 203). The 10-year survival rates were 74.9% with CABG, 75.1% with PCI, and 69% with MT (P = 0.089). The 10-year rates of myocardial infarction were 10.3% with CABG, 13.3% with PCI, and 20.7% with MT (P < 0.010). The 10-year rates of additional revascularizations were 7.4% with CABG, 41.9% with PCI, and 39.4% with MT (P < 0.001). Relative to the composite end point, Cox regression analysis showed a higher incidence of primary events in MT than in CABG (hazard ratio 2.35, 95% confidence interval 1.78 to 3.11) and in PCI than in CABG (hazard ratio 1.85, 95% confidence interval 1.39 to 2.47). Furthermore, 10-year rates of freedom from angina were 64% with CABG, 59% with PCI, and 43% with MT (P < 0.001). Conclusions-Compared with CABG, MT was associated with a significantly higher incidence of subsequent myocardial infarction, a higher rate of additional revascularization, a higher incidence of cardiac death, and consequently a 2.29-fold increased risk of combined events. PCI was associated with an increased need for further revascularization, a higher incidence of myocardial infarction, and a 1.46-fold increased risk of combined events compared with CABG. Additionally, CABG was better than MT at eliminating anginal symptoms.

Streptokinase and Enoxaparin as an Alternative to Fibrin-Specific Lytic-Based Regimens An ExTRACT-TIMI 25 Analysis

Background: Enoxaparin was superior to unfractionated heparin (UFH), regardless of fibrinolytic agent in ST-elevation myocardial infarction (STEMI) patients receiving fibrinolytic therapy in ExTRACT-TIMI 25 (Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment Thrombolysis in Myocardial Infarction 25) trial. Objective: This post hoc analysis compared outcomes with streptokinase plus enoxaparin to the standard regimen of fibrin-specific lytic (FSL) plus UFH and to the newer combination of FSL plus enoxaparin. Methods: In ExTRACT-TIMI 25, STEMI patients received either streptokinase or a FSL (alteplase, reteplase or tenecteplase) at the physician`s discretion and were randomized to enoxaparin or UFH, stratified by fibrinolytic type. Thirty-day outcomes were adjusted for baseline characteristics, region, in-hospital percutaneous coronary intervention (PCI) and a propensity score for the choice of lytic. Results: The primary trial endpoint of 30-day death/myocardial infarction (MI) occurred in fewer patients in the streptokinase-enoxaparin cohort (n = 2083) compared with FSL-UFH (n = 8141) [10.2% vs 12.0%, adjusted odds ratio [OR(adj)] 0.76; 95% CI 0.62, 0.93; p = 0.008]. Major bleeding was significantly increased with streptokinase-enoxaparin compared with FSL-UFH (ORadj 2.74; 95% CI 1.81; 4.14; p < 0.001) but intracranial haemorrhage (ICH) was similar (OR(adj) 0.90; 95% CI 0.40, 2.01; p = 0.79). Net clinical outcomes, defined as either death/MI/major bleeding or as death/MI/ICH tended to favour streptokinase-enoxaparin compared with FSL-UFH (OR(adj) 0.88; 95% CI 0.73, 1.06; p = 0.17; and OR(adj) 0.77; 95% CI 0.63, 0.93; p = 0.008, respectively). Patients receiving FSL-enoxaparin (n = 8142) and streptokinase-enoxaparin therapies experienced similar adjusted rates of the primary endpoint (OR(adj) 1.08; 95% CI 0.87, 1.32; p = 0.49) and net clinical outcomes. Conclusions: Our results suggest that fibrinolytic therapy with the combination of streptokinase and the potent anticoagulant agent enoxaparin resulted in similar adjusted outcomes compared with more costly regimens utilizing a FSL.

Analyzing the connectivity between regions of interest: An approach based on cluster Granger causality for NRI data analysis

The identification, modeling, and analysis of interactions between nodes of neural systems in the human brain have become the aim of interest of many studies in neuroscience. The complex neural network structure and its correlations with brain functions have played a role in all areas of neuroscience, including the comprehension of cognitive and emotional processing. Indeed, understanding how information is stored, retrieved, processed, and transmitted is one of the ultimate challenges in brain research. In this context, in functional neuroimaging, connectivity analysis is a major tool for the exploration and characterization of the information flow between specialized brain regions. In most functional magnetic resonance imaging (fMRI) studies, connectivity analysis is carried out by first selecting regions of interest (ROI) and then calculating an average BOLD time series (across the voxels in each cluster). Some studies have shown that the average may not be a good choice and have suggested, as an alternative, the use of principal component analysis (PCA) to extract the principal eigen-time series from the ROI(s). In this paper, we introduce a novel approach called cluster Granger analysis (CGA) to study connectivity between ROIs. The main aim of this method was to employ multiple eigen-time series in each ROI to avoid temporal information loss during identification of Granger causality. Such information loss is inherent in averaging (e.g., to yield a single ""representative"" time series per ROI). This, in turn, may lead to a lack of power in detecting connections. The proposed approach is based on multivariate statistical analysis and integrates PCA and partial canonical correlation in a framework of Granger causality for clusters (sets) of time series. We also describe an algorithm for statistical significance testing based on bootstrapping. By using Monte Carlo simulations, we show that the proposed approach outperforms conventional Granger causality analysis (i.e., using representative time series extracted by signal averaging or first principal components estimation from ROIs). The usefulness of the CGA approach in real fMRI data is illustrated in an experiment using human faces expressing emotions. With this data set, the proposed approach suggested the presence of significantly more connections between the ROIs than were detected using a single representative time series in each ROI. (c) 2010 Elsevier Inc. All rights reserved.

Mammography findings following electron intraoperative radiotherapy or external radiotherapy for breast cancer treatment

Radiotherapy following breast cancer conserving surgery decreases the risks of local recurrence. Because 85% of breast cancers relapse in or around the surgical bed there has been some debate on the need for irradiating the whole breast. Electron intraoperative radiotherapy (ELIOT) has been used as a viable alternative for conventional external radiotherapy (RT). While the former requires a single dose of 21 Gy in the tumoral bed, the latter requires 5-6 weeks of irradiation with a total dose of 50 Gy and a boost of 10 Gy that irradiates the surgical bed. Herein, we investigated whether any significant differences exist between the mammography findings obtained from patients submitted to one of the two techniques. Two groups of 30 patients each were included in this study. All patients had mammographies taken at 12 and 24 months after finishing treatment. The mammography findings evaluated were: cutaneous thickening (>2 mm), architectural distortion secondary to fibrosis, edema, calcifications (both benign and malignant), and fat necrosis. For all variables studied, there was no statistical difference between the two groups. This indicates that the mammography findings obtained in either 12- or 24-month follow-up periods after breast cancer conserving surgery are similar, regardless of which of the two radiotherapy techniques (ELIOT or RT) is employed as a treatment for breast cancer. (C) 2010 Published by Elsevier Ireland Ltd.

Issues in geriatric medicine

In Australia there has been rapid growth in the number of geriatricians and the provision of aged care services. This has been accompanied by increasing sophistication in the assessment and management of the common syndromes of old age: impaired cognition, incontinence, impaired mobility, impaired homeostasis and iatrogenic disease. Innovative systems of service delivery have been developed in diverse fields including dementia services and orthogeriatrics. Adequate planning and funding strategies are required to ensure that older people continue to have appropriate access to high quality services and that there is provision for education and research in ageing.

Midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation

PURPOSE: To evaluate retrospectively the midterm and long-term results of percutaneous endovascular treatment of venous outflow obstruction after pediatric liver transplantation. MATERIALS AND METHODS: During a 9-year period, 18 children with obstruction of a hepatic vein (HV) or inferior vena cava (IVC) anastomosis underwent percutaneous transluminal angioplasty (PTA) with balloon dilation or stent placement in case of PTA failure after liver transplantation. Patients` body weights ranged from 7.7 kg to 42.6 kg (mean, 18.8 kg +/- 9). Potential predictors of patency were compared between balloon dilation and stent placement groups. RESULTS: Forty-two procedures were performed (range, 1-11 per patient; mean, 2). Technical and initial clinical success were achieved in all cases. Major complications included one case of pulmonary artery stent embolization and one case of hemothorax. Three children (25%) with HV obstruction were treated with PTA and nine (75%) were treated with stent placement. Three children with IVC obstruction (75%) were treated with PTA and one (25%) was treated with a stent. There were two children with simultaneous obstruction at the HV and IVC; one was treated with PTA and the other with a stent. Cases of isolated HV stenosis have a higher probability of patency with balloon-expandable stent treatment compared with balloon dilation (P < .05). Follow-up time ranged from 7 days to 9 years (mean, 42 months +/- 31), and the primary assisted patency rate was 100% when stent placement was performed among the first three procedures. CONCLUSIONS: In cases of venous outflow obstruction resulting from HV and/or IVC lesions after pediatric liver transplantation, percutaneous endovascular treatment with balloon dilation or stent placement is a safe and effective alternative treatment that results in long-term patency.

Autopathogenic T helper cell type 1 (Th1) and protective Th2 clones differ in their recognition of the autoantigenic peptide of myelin proteolipid protein

We previously generated a panel of T helper cell 1 (Th1) clones specific for an encephalitogenic peptide of myelin proteolipid protein (PLP) peptide 139-151 (HSLGKWLGHPDKF) that induces experimental autoimmune encephalomyelitis (EAE) upon adoptive transfer. In spite of the differences in their T cell receptor (TCR) gene usage, all these Th1 clones required W144 as the primary and most critical TCR contact residue for the activation. In this study, we determined the TCR contact residues of a panel of Th2/Th0 clones specific for the PLP peptide 139-151 generated either by immunization with the PLP 139-151 peptide with anti-B7-1 antibody or by immunization with an altered peptide Q144. Using alanine-substituted peptide analogues of the native PLP peptide, we show that the Th2 clones have shifted their primary contact residue to the NH2-terminal end of the peptide. These Th2 cells do not show any dependence on the W144, but show a critical requirement for L141/G142 as their major TCR contact residue. Thus, in contrast with the Th1 clones that did not proliferate to A144-substituted peptide, the Th2 clones tolerated a substitution at position 144 and proliferated to A144 peptide. This alternative A144 reactive repertoire appears to have a critical role in the regulation of autoimmune response to PLP 139-151 because preimmunization with A144 to expand the L141/G142-reactive repertoire protects mice from developing EAE induced with the native PLP 139-151 peptide. These data suggest that a balance between two different T cell repertoires specific for same autoantigenic epitope can determine disease phenotype, i.e., resistance or susceptibility to an autoimmune disease.