Citations

AbstractBackgroundA pooled post hoc responder analysis was performed to assess the clinical benefit of alvimopan, a peripherally acting mu‐opioid receptor (PAM‐OR) antagonist, for the management of postoperative ileus after bowel resection.MethodsAdult patients who underwent laparotomy for bowel resection scheduled for opioid‐based intravenous patient‐controlled analgesia received oral alvimopan or placebo preoperatively and twice daily postoperatively until hospital discharge or for 7 postoperative days. The proportion of responders and numbers needed to treat (NNT) were examined on postoperative days (POD) 3–8 for GI‐2 recovery (first bowel movement, toleration of solid food) and hospital discharge order (DCO) written.ResultsAlvimopan significantly increased the proportion of patients with GI‐2 recovery and DCO written by each POD (P < 0.001 for all). More patients who received alvimopan achieved GI‐2 recovery on or before POD 5 (alvimopan, 80%; placebo, 66%) and DCO written before POD 7 (alvimopan, 87%; placebo, 72%), with corresponding NNTs equal to 7.ConclusionsOn each POD analyzed, alvimopan significantly increased the proportion of patients who achieved GI‐2 recovery and DCO written versus placebo and was associated with relatively low NNTs. The results of these analyses provide additional characterization and support for the overall clinical benefit of alvimopan in patients undergoing bowel resection.

Background and Purpose— Recombinant Factor VIIa decreases hematoma growth after spontaneous intracerebral hemorrhage (ICH) and rapidly decreases international normalized ratios in patients on warfarin but is also associated with an increased risk for thromboembolic complications. In this study, we assessed the risk of thromboembolic events in patients receiving recombinant Factor VIIa after ICH associated with warfarin treatment. Methods— We reviewed the medical charts, laboratory data, and radiological findings of consecutive patients with anticoagulation-related hemorrhages of the central nervous system who received recombinant Factor VIIa at Mayo Clinic Rochester and Mayo Clinic Florida between 2002 and 2009. The primary end point was the frequency of new thromboembolic events, including myocardial infarction, deep vein thrombosis, ischemic stroke, and pulmonary embolism. Results— We identified 101 patients; 54% had ICH and 30% subdural hematomas. The most common indications for anticoagulation were atrial fibrillation, deep vein thrombosis, and prosthetic valve. Thirteen patients (12.8%) had new thromboembolic events (10 deep vein thromboses and 3 ischemic strokes) within 90 days after recombinant Factor VIIa administration. Eight of these adverse events occurred within 2 weeks of treatment. In patients with ICH, the rate of thromboembolic complications was 5% and all events were venous. Conclusion— The risk of thromboembolic events in patients who received recombinant Factor VIIa for anticoagulation-associated ICH was not higher than that seen in patients treated for spontaneous ICH in the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial. Spontaneous deep vein thrombosis was the most common complication in our series.

ABSTRACT Campylobacter jejuni and Salmonella , Shigella , and Yersinia species (along with Shiga toxin-producing Escherichia coli ) are the most common causes of acute bacterial diarrheal disease in the United States. Current detection techniques are time-consuming, limiting usefulness for patient care. We developed and validated a panel of rapid PCR assays for the detection and identification of C. jejuni , C. coli , Salmonella , and Yersinia species and Shigella and enteroinvasive E. coli in stool samples. A total of 392 archived stool specimens, previously cultured for enteric pathogens, were evaluated by PCR. Overall, 104 stool specimens had been culture positive ( C. jejuni / coli [ n = 51], Salmonella species [ n = 42], Shigella species [ n = 6], and Yersinia species [ n = 5]). Compared to culture, the overall sensitivity and specificity of PCR detection of these organisms were 92 and 98% (96/104 and 283/288), respectively, from fresh or Cary Blair stool ( P = 0.41); 87 and 98% (41/47 and 242/246), respectively, from fresh stool ( P = 0.53); and 96 and 98% (55/57 and 41/42), respectively, from Cary Blair stool ( P = 0.56). For individual genera, PCR was as sensitive as the culture method, with the exception of Salmonella culture using selenite enrichment for which PCR was less sensitive than culture from fresh, but not Cary Blair ( P = 0.03 and 1.00, respectively) stools. This PCR assay panel for the rapid diagnosis of acute infectious bacterial diarrheal pathogens has a sensitivity and specificity equivalent to that of culture for stools in Cary Blair transport medium. Paired with reflexive culture of stools testing positive, this should provide an improvement in care for patients with acute infectious diarrheal disease.

The authors describe the case of a 36-year-old man with gynecomastia who was previously treated with liposuction of the breast for cosmetic purposes. Histologic examination of a subsequent excisional biopsy revealed nests of displaced epithelial cells in adipose tissue. Epithelial cell displacement is a well-known risk of core needle biopsies and fine-needle aspirations of breast lesions. However, to the authors’ knowledge, epithelial displacement in gynecomastia after liposuction, mimicking invasive ductal carcinoma, has not previously been reported.

Abstract The low efficiency of reprogramming and genomic integration of virus vectors obscure the potential application of induced pluripotent stem (iPS) cells; therefore, identification of chemicals and cooperative factors that may improve the generation of iPS cells will be of great value. Moreover, the cellular mechanisms that limit the reprogramming efficiency need to be investigated. Through screening a chemical library, we found that two chemicals reported to upregulate E-cadherin considerably increase the reprogramming efficiency. Further study of the process indicated that E-cadherin is upregulated during reprogramming and the established iPS cells possess E-cadherin-mediated cell–cell contact, morphologically indistinguishable from embryonic stem (ES) cells. Our experiments also demonstrate that overexpression of E-cadherin significantly enhances reprogramming efficiency, whereas knockdown of endogenous E-cadherin reduces the efficiency. Consistently, abrogation of cell–cell contact by the inhibitory peptide or the neutralizing antibody against the extracellular domain of E-cadherin compromises iPS cell generation. Further mechanistic study reveals that adhesive binding activity of E-cadherin is required. Our results highlight the critical role of E-cadherin-mediated cell–cell contact in reprogramming and suggest new routes for more efficient iPS cell generation.

AbstractPurpose: The purpose of this article is to present a brief description of the neuroanatomical correlates, pathophysiology, and clinical presentation of corticobasal ganglionic degeneration, (often referred to as corticobasal degeneration, or CBD) and progressive supranuclear palsy (PSP).Methods: Descriptions of the clinical characteristics of the two degenerative syndromes are presented, including a discussion of the similarities and differences. The speech and language disorders associated with each are described, including progressive aphasia, progressive non-fluent aphasia (PNFA), progressive apraxia of speech (AOS), and dysarthria.Results and Conclusions: CBD and PSP have a number of commonalities in clinical characteristics and in pathology. Both progressive aphasia and apraxia of speech have been associated with CBD and PSP. Clinicians who evaluate patients exhibiting a progressive neurologic disease and who identify either progressive aphasia, PNFA and/or progressive AOS should consider CBD or PSP as a possible medical diagnosis.

AbstractThe antithrombotic surface of endothelium is regulated in a coordinated manner. Tissue factor pathway inhibitor (TFPI) localized at the endothelial cell surface regulates the production of FXa by inhibiting the TF/VIIa complex. Systemic homozygotic deletion of the first Kunitz (K1) domain of TFPI results in intrauterine lethality in mice. Here we define the cellular sources of TFPI and their role in development, hemostasis, and thrombosis using TFPI conditional knockout mice. We used a Cre-lox strategy and generated mice with a floxed exon 4 (TFPIFlox) which encodes for the TFPI-K1 domain. Mice bred into Tie2-Cre and LysM-Cre lines to delete TFPI-K1 in endothelial (TFPITie2) and myelomonocytic (TFPILysM) cells resulted in viable and fertile offspring. Plasma TFPI activity was reduced in the TFPITie2 (71% ± 0.9%, P < .001) and TFPILysM (19% ± 0.6%, P < .001) compared with TFPIFlox littermate controls. Tail and cuticle bleeding were unaffected. However, TFPITie2 mice but not TFPILysM mice had increased ferric chloride–induced arterial thrombosis. Taken together, the data reveal distinct roles for endothelial- and myelomonocytic-derived TFPI.

Abstract Purpose: Deep brain stimulation (DBS) is a surgical option which has been demonstrated to be effective for treatment of many symptoms in several movement disorders. The purpose of this paper is to describe this surgical option and to discuss its effects on motor speech. Method: The literature is reviewed to provide a summary of the information available to describe DBS surgery and its effects on motor speech in neurological disorders. Primary focus is placed on DBS as a treatment for Parkinson's disease (PD) and Essential Tremor (ET). Results and Conclusions: DBS surgery is a relatively low-risk, common, and reversible surgery used to treat the motor symptoms in many movement disorders, especially PD and ET. It is not currently used as a treatment for any motor speech disorder. Dysarthria is a commonly reported side-effect of bilateral more than unilateral DBS surgery. The reported frequency of motor speech difficulties varies, and few studies have specifically examined motor speech with reliable and objective measures. However, though frequently present, negative effects of DBS on motor speech appear to be mild in severity.