Chronic segmental spinal muscular atrophy of upper extremities in identical twins

We present the 1st report of chronic segmental spinal muscular atrophy confined to the upper extremities in identical male twins. This occurrence in identical twins, together with reports of siblings and parent-child pairs of a disorder phenotypically similar to the more common sporadic form in the literature, suggests a genetic etiology in some cases.     

Evaluation Of 5-hydroxy-2,3-diaryl (substituted)-cyclopent-2-en-1-ones as <Emphasis Type="Italic">cis</Emphasis>-restricted analogues of combretastatin A-4 as novel anti angiogenic and anticancer agents

Two potent cis-restricted CA-4 analogues 11 and 42 belonging to 2,3-diaryl-5-hydroxycyclopent-2-en-1-one class were evaluated for anticancer and anti angiogenic activity. The compound 42 displayed potent cytotoxic activity (IC₅₀ < 1 μM) against a panel of human cancer cell lines viz PTC, MDA.MB.453, PA1, SKOV3, DU145 and Miapaca2, whereas compound 11 displayed cytotoxicity activity (IC₅₀ < 1 μM) only in Miapaca2. Both the compounds inhibit growth factor stimulated endothelial cell proliferation, migration and capillary tube formation. In all the above parameter compound 42 was superior to 11. Based on the above results compound 42 was assessed for inhibition of vasculature in vivo and showed significant inhibition at 25 mg/kg dose. Further it was evaluated for in vivo anti tumor activity in athymic mice bearing DU145 and SKVO3 tumor xenograft and showed regression in tumor volume (T/C) of 23.8% (CA-4), 50.1% (compound 42) and 23.5% (CA-4), 56% (compound 42) respectively at a dose of 20 mg/kg (i.v.) daily for 14 days.     

Antibodies to Epstein-Barr virus in patients with chronic fatigue.

To clarify the role of Epstein-Barr virus (EBV) infection and the value of EBV antibody testing in evaluating patients with chronic fatigue, we studied 200 consecutive patients with chronic fatigue (mean duration, 9 years). Complete EBV serologic panels were obtained for 154 patients, 35 (23%) of whom met serologic or clinical criteria for chronic or reactivated EBV infection. We compared these patients with chronic EBV infection (CEBV cases) to 35 age- and sex-matched patients who were selected from the same cohort of fatigued patients but who did not meet the criteria (CEBV control subjects). We found few differences between groups in demographic characteristics, clinical features, and symptoms; CEBV cases were more likely to meet criteria for the proposed chronic fatigue syndrome (14% vs 0%), and to report that they suffered from an influenza-like illness at the onset of their fatigue syndrome (34% vs 12%), that they lost their job because of their fatigue (37% vs 11%), and that their fatigue was improved by recreational activity (26% vs 3%). Physical examination and laboratory testing showed few abnormalities in either group. Psychiatric morbidity was common in both groups, including mood disorders (63% of CEBV cases vs 54% of CEBV controls), anxiety (11% vs 9%) and somatization disorder (9% in each group). We conclude that EBV serologic patterns have little clinical usefulness in evaluating patients with chronic fatigue.     

Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. II. Recommendations

Objective Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been increasingly recognized in the critically ill over the past decade. In the absence of consensus definitions and treatment guidelines the diagnosis and management of IAH and ACS remains variable from institution to institution. Design An international consensus group of multidisciplinary critical care specialists convened at the second World Congress on Abdominal Compartment Syndrome to develop practice guidelines for the diagnosis, management, and prevention of IAH and ACS. Methods Prior to the conference the authors developed a blueprint for consensus definitions and treatment guidelines which were refined both during and after the conference. The present article is the second installment of the final report from the 2004 International ACS Consensus Definitions Conference and is endorsed by the World Society of the Abdominal Compartment Syndrome. Results The prevalence and etiological factors for IAH and ACS are reviewed. Evidence-based medicine treatment guidelines are presented to facilitate the diagnosis and management of IAH and ACS. Recommendations to guide future studies are proposed. Conclusions These definitions, guidelines, and recommendations, based upon current best evidence and expert opinion are proposed to assist clinicians in the management of IAH and ACS as well as serve as a reference for future clinical and basic science research.     

Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study

Objective Although intra-abdominal hypertension (IAH) can cause dysfunction of several organs and raise mortality, little information is available on the incidence and risk factors for IAH in critically ill patients. This study assessed the prevalence of IAH and its risk factors in a mixed population of intensive care patients.Design A multicentre, prospective 1-day point-prevalence epidemiological study conducted in 13 ICUs of six countries.Interventions None.Patients Ninety-seven patients admitted for more than 24 h to one of the ICUs during the 1-day study period.Methods Intra-abdominal pressure (IAP) was measured four times (every 6 h) by the bladder pressure method. Data included the demographics, medical or surgical type of admission, SOFA score, etiological factors such as abdominal surgery, haemoperitoneum, abdominal infection, massive fluid resuscitation, and ileus and predisposing conditions such as hypothermia, acidosis, polytransfusion, coagulopathy, sepsis, liver dysfunction, pneumonia and bacteraemia.Results We enrolled 97 patients, mean age 64±15 years, 57 (59%) medical and 40 (41%) surgical admission, SOFA score of 6.5±4.0. Mean IAP was 9.8±4.7 mmHg. The prevalence of IAH (defined as IAP 12 mmHg or more) was 50.5 and 8.2% had abdominal compartment syndrome (defined as IAP 20 mmHg or more). The only risk factor significantly associated with IAH was the body mass index, while massive fluid resuscitation, renal and coagulation impairment were at limit of significance.Conclusion Although we found a quite high prevalence of IAH, no risk factors were reliably associated with IAH; consequently, to get valid information about IAH, IAP needs to be measured.     

Active transforming growth factor-β1 activates the procollagen I promoter in patients with acute lung injury

Objective Fibroproliferation markers like procollagen I predict mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). We sought to determine whether bronchoalveolar lavage fluid (BALF) from patients with lung injury contained mediators that would activate procollagen I promoter and if this activation predicted important clinical outcomes.Design Prospective controlled study of ALI/ARDS.Setting Intensive care units and laboratory of a university hospital.Patients and participants Acute lung injury/ARDS, cardiogenic edema (negative controls) and pulmonary fibrosis (positive controls) patients.Interventions Bronchoalveolar lavage fluid was collected within 48 h of intubation from ALI/ARDS patients. BALF was also collected from patients with pulmonary fibrosis and cardiogenic pulmonary edema. Human lung fibroblasts were transfected with a procollagen I promoter-luciferase construct and incubated with BALF; procollagen I promoter activity was then measured. BALF active TGF-1 levels were measured by ELISA.Results Twenty-nine ARDS patients, nine negative and six positive controls were enrolled. BALF from ARDS patients induced 41% greater procollagen I promoter activation than that from negative controls (p<0.05) and a TGF-1 blocking antibody significantly reduced this activation in ARDS patients. There was a trend toward higher TGF-1 levels in the ARDS group compared to negative controls (–1.056 log₁₀±0.1415 vs –1.505 log₁₀±0.1425) (p<0.09). Procollagen I promoter activation was not associated with mortality; however, lower TGF-1 levels were associated with more ventilator-free and ICU-free days.Conclusions Bronchoalveolar lavage fluid from ALI/ARDS patients activates procollagen I promoter, which is due partly to TGF-1. Activated TGF-1 may impact ARDS outcome independent of its effect on procollagen I activation.Electronic Supplementary Material Supplementary material is available in the online version of this article at     

Variability in interventions with pulmonary artery catheter data

Objectives To determine if intensivists given PAC data from critically ill patients make uniform management choices.Design Cross-sectional survey of board-certified intensivists.Setting Medical intensive care unit.Participants Board-certified intensivists who are members of the American College of Chest Physicians and Society of Critical Care Medicine.Interventions A survey questionnaire containing three medical intensive care clinical vignettes was mailed to critical care physicians. Each vignette contained PAC data and one-half of the surveys contained echocardiographic (Echo) information. Every respondent was asked to select one of six interventions for each vignette.Measurements There were 126 evaluable surveys returned. In vignette 1 an intervention (none of the above) was selected by more than 50% of respondents. In vignettes 2 and 3, the most frequent selection was chosen only 44 and 37% of the times, respectively. There was a significant difference in the distribution of management choices between the Echo and the non-Echo subgroups.Conclusions There is significant heterogeneity in selecting an intervention based on PAC data among intensivists. The presence of Echo information may change the intervention selected but does not reduce heterogeneity. Any randomized trial evaluating efficacy of PACs will have to have strict treatment protocols.Electronic Supplementary Material Supplementary material is available in the online version of this article at An editorial regarding this article can be found in the same issue ()     

Serial assessment of functional recovery following nerve injury using implantable thin‐film wireless nerve stimulators

Introduction: Comprehensive assessment of the time course of functional recovery following peripheral nerve repair is critical for surgical management of peripheral nerve injuries. This study describes the design and implementation of a novel implantable wireless nerve stimulator capable of repeatedly interfacing peripheral nerve tissue and providing serial evaluation of functional recovery postoperatively. Methods: Thin‐film wireless implants were fabricated and subcutaneously implanted into Lewis rats. Wireless implants were used to serially stimulate rat sciatic nerve and assess functional recovery over 3 months following various nerve injuries. Results: Wireless stimulators demonstrated consistent performances over 3 months in vivo and successfully facilitated serial assessment of nerve and muscle function following nerve crush and nerve transection injuries. Conclusions: This study highlights the ability of implantable wireless nerve stimulators to provide a unique view into the time course of functional recovery in multiple motor targets. Muscle Nerve 54 : 1114–1119, 2016