bluuebunny/crossref_metadata_2025 huggingface dataset:
Hartmann’s Procedure or Primary Anastomosis?
Authors: Kreis Martin E. , Mueller Mario H. , Thasler Wolfgang H.
Published: May 2012

Perforation following acute diverticulitis is a typical scenario during the first attack. Different classification systems exist to classify acute perforated diverticulitis. While the Hinchey classification, which is based on intraoperative findings, is internationally best known, the German Hansen-Stock classification which is based on CT scan is widely accepted within Germany. When surgery is necessary, sigmoid colectomy is the standard of care. An important question is whether patients should receive primary anastomosis or a Hartmann procedure subsequently. A priori there are several arguments for both procedures. Hartmann’s operation is extremely safe and, therefore, represents the best option in severely ill patients and/or extensive peritonitis. However, this operation carries a high risk of stoma nonreversal, or, when reversal is attempted, a high risk in terms of morbidity and mortality. In contrast, primary anastomosis with or without loop ileostoma is a slightly more lengthy procedure as normally the splenic flexure needs to be mobilized and construction of the anastomosis may consume more time than the Hartmann operation. The big advantage of primary anastomosis, however, is that there is no need for the potentially risky stoma reversal operation. The most interesting question is when to do the Hartmann operation or primary anastomosis. Several comparative case series were published showing that primary anastomosis is feasible in many patients. However, no randomized trial is available to date. It is of note, that all non-randomized case series are biased, i.e. that patients in better condition received anastomosis and those with severe peritonitis underwent Hartmann’s operation. This bias is undoubtedly likely to be present, even if not obvious, in the published papers! Our own data suggest that this decision should not be based on the extent of peritonitis but rather on patient condition and comorbidity. In conclusion, sigmoid colectomy and primary anastomosis is feasible and safe in many patients who need surgery for perforated diverticulitis, particularly when combined with loop ileostomy. Based on our own published analysis, however, we recommend performing Hartmann’s operation in severely ill patients who carry substantial comorbidity, while the extent of peritonitis appears not to be of predominant importance.
The Surgeon’s View
Authors: Senapati Asha
Published: May 2012

Diverticular disease affects up to 50% of people by the time they reach the age of 80. The major complications of diverticular disease (abscess, perforation, fistula, obstruction and bleeding) have their own management pathways, but the treatment of uncomplicated diverticulitis is controversial. On initial presentation, diverticulitis is always treated conservatively. Whether this should be followed by resectional surgery has been the subject of speculation for many decades. The American Society of Colon and Rectal Surgeons recommended in 2000 that an elective resection should follow two attacks of acute diverticulitis. Much of the work underpinning their policy was based on seminal studies by Parks in the 1960s and 1970s who followed cohorts of patients with diverticular disease and examined their outcomes. However, many of these studies were based on inaccurate diagnostic data where the diagnosis was made primarily on clinical grounds. Investigations such as barium enema or colonoscopy are not reliable in confirming the presence of inflammation. Since CT scanning has become routine, the diagnosis of acute diverticulitis can now be made accurately. In recent years much work has been done, such as by Ambrosetti, who has produced evidence predicting the outcome of diverticulitis based on CT findings. More recent papers, in which the diagnosis of acute diverticulitis is likely to have been made more accurately, confirm that although recurrent attacks of diverticulitis are fairly common, there is a very low incidence of serious complications after long-term follow-up. It has also become apparent that the majority of patients who present with the major complications of diverticulitis, specifically abscess, perforation and fistula, do so as their first presentation of the disease, without previous episodes of diverticulitis. The corollary of this is that patients having had acute diverticulitis do not run the risk of developing life-threatening complications without elective surgery. The complications of left-sided colonic resection are not inconsiderable with anastomotic leaks, the formation of a stoma, either temporary or permanent, as well as mortality. When these data are put alongside the very low risk of serious harm to the patient after diverticulitis, the balance of opinion has now swung heavily in favour of a more conservative approach. In addition to this there are modern and innovative medical therapeutic approaches to the treatment of diverticulitis such as 5ASAs, poorly absorbed antibiotics and probiotics.
Role of Endoscopy in Patients with Diverticular Disease
Authors: Bar-Meir Simon , Lahat Adi , Melzer Ehud
Published: May 2012

Acute diverticulitis occurs in 10–25% of patients with diverticulosis. Colonoscopy is advised 6 weeks after an attack of acute diverticulitis in order to completely evaluate the colonic lumen and exclude a potential malignancy. We conducted several studies aimed to evaluate the feasibility and safety of early colonoscopy in patients with acute diverticulitis. Consecutive patients hospitalized for acute diverticulitis were included. In the first phase of the study, patients with adjacent peri-diverticular air/fluid on CT were excluded. In the second phase of the study, we included patients with peri-diverticular air/fluid on CT as well. During the first phase of the study, 39 patients underwent uneventful colonoscopy. During the second phase of the study, 40 patients underwent colonoscopy and 1 of 6 patients with peri-diverticular air had perforation of her sigmoid colon. Two patients had a more protracted course and were clearly those who benefited most from the early colonoscopy. Based on our study, we concluded that early colonoscopy in acute diverticulitis is feasible. It should be reserved either for all patients with no air adjacent to diverticuli on CT or just for those with a more protracted course. In the third phase, a prospective randomized study was conducted on patients with acute diverticulitis with no peri-diverticular air. Such patients were randomized into those who underwent early colonoscopy and those who underwent colonoscopy 6 weeks later. Eighty-three patients were included in both groups and in none has a significant lesion been identified (except polyps). It seems therefore that the current abdominal CT with its excellent resolution is enough to exclude colonic cancer. Colonoscopy should be reserved only for patients with a protracted unresolved course of acute diverticulitis.
Overtreatment of Sigmoid Diverticulitis: Plea for a Less Aggressive Approach
Authors: Daniels L. , de Korte N. , Winter D. , Boermeester M.A. , Stockmann H.B.A.C.
Published: May 2012

A less invasive approach to the treatment of left-sided colonic diverticulitis has emerged in the last decade. The standard of care for perforated or complicated diverticulitis evolved from a Hartmann’s procedure, to resection and primary anastomosis, to treatment with antibiotics and percutaneous drainage in a carefully selected (Hinchey grade 2) patient subset. Recently, laparoscopic lavage emerged as a promising less invasive treatment for selected cases of Hinchey 3 patients. Likewise, for nonperforated or uncomplicated diverticulitis the approach is becoming less aggressive with a change from intravenous antimicrobial therapy, starvation and admission, to oral antibiotics and finally to observation and outpatient treatment. This less invasive or aggressive approach is due to expanding evidence on optimal treatment and is congruent with an increasing understanding that diverticulitis comprises different disease entities with heterogeneity between patients. The disease should be targeted by specific approaches, after a meticulous assessment of the diverticulitis stage, and tailored to an individual basis. Avoidance of overtreatment has obvious benefits: less in-hospital treatment, cost reduction, diminished development of antimicrobial resistance, reduction in complication rate and side effects and presumably a better quality of life for the patient. In conclusion, one might say we have overtreated the majority of diverticulitis patients for decades. More research is needed to explain the pathogenesis and multifactorial etiology and in the near future hopefully several unanswered questions regarding the optimal management of patients with different stages of diverticulitis will be answered by various ongoing trials.
Comprehensive Staging Surgery Including Complete Pelvic and Para-Aortic Lymphadenectomy Followed by Adjuvant Vaginal Brachytherapy Improves Survival Rates for Intermediate-Risk Endometrial Cancer Patients
Authors: Kong Tae Wook , Paek Jiheum , Chang Suk-Joon , Chun Mison , Chang Ki-Hong , Ryu Hee-Sug
Published: May 2012

Aim: To investigate the survival of patients with intermediate-risk endometrial cancer treated with comprehensive staging surgery including complete pelvic and para-aortic lymphadenectomy and adjuvant vaginal brachytherapy (VBT). Methods: Between January 2000 and December 2009, we retrospectively reviewed the medical records of 156 patients who underwent comprehensive surgical staging consisting of total hysterectomy, adnexectomy, peritoneal cytology, and complete pelvic/para-aortic lymphadenectomy. There were 122 low-risk and 34 intermediate-risk patients, and intermediate-risk patients received adjuvant VBT. Results: During the follow-up period, 7 (4.5%) of the 156 patients developed recurrent disease: 3 (2.5%) of the 122 low-risk and 4 (11.8%) of the 34 intermediate-risk patients. Among the 7 patients with recurrent disease, only 1 intermediate-risk patient died of disease and 6 stayed alive for the rest of the follow-up period. Disease-free survival at 5 years was 95.7% in the low-risk patients and 81.6% in the intermediate-risk patients, and this difference was statistically significant (p = 0.009). There was no statistically significant difference in overall survival at 5 years between the two groups (100% in low-risk patients vs. 96.7% in intermediate-risk patients, p = 0.061). Overall, grade 3 toxicities were seen in 1 (2.9%) patient. Conclusion: Comprehensive staging surgery including complete pelvic and para-aortic lymphadenectomy followed by adjuvant VBT improves survival rates for intermediate-risk endometrial cancer patients, which are comparable with those of low-risk patients.
A Case of Therapy-Related Myeloid Neoplasm in a Patient with Crohn’s Disease Treated with Azathioprine
Authors: Mullier François , Rahier Jean-François , Maignen François , Cornet Yvan , Graux Carlos , Chatelain Christian , Chatelain Bernard , Dogne Jean-Michel
Published: May 2012

Acute leukaemia (AL) has been observed in association with Crohn’s disease (CD) notably in patients treated with azathioprine (AZA), which is an immunosuppressant known for its carcinogenicity and in particular known to induce therapy-related acute myeloid leukaemia according to the 2008 WHO classification. Whereas the link between inflammatory bowel disease and AL has been well established, the exact role of AZA remains controversial. In this paper, we report the case of a 71-year-old white Caucasian male with CD treated for 7 years with AZA who developed an acute leukaemia. Chemotherapy was administered unsuccessfully and the patient died from this haematological disorder 9 months after diagnosis. We reviewed the current evidence on the interactions between CD, AL and AZA as well as the potential underlying mechanisms of leukaemia in AZA-treated patients. From this review, we concluded that AL should be questioned when facing cytopenia in a patient with CD. The nature of the association between AZA and AL in CD patients warrants further investigation.
Postoperative Hematological Changes after Spleen-Preserving Distal Pancreatectomy with Preservation of the Splenic Artery and Vein
Authors: Tezuka Koji , Kimura Wataru , Hirai Ichiro , Moriya Toshiyuki , Watanabe Toshihiro , Yano Mitsuhiro
Published: May 2012

Background: The aim of this study was to determine the early postoperative hematological changes after spleen-preserving distal pancreatectomy (SpDP) with preservation of the splenic artery and vein (PSAV). Methods: We reviewed 53 patients who underwent SpDP with PSAV (n = 21) or distal pancreatectomy with splenectomy (DPS; n = 32) for benign or low-grade malignant lesions between July 1998 and June 2010. Red and white blood cell (WBC) count, platelet count, serum hemoglobin, hematocrit, C-reactive protein, albumin level, and clinical factors were compared between the SpDP with PSAV and DPS. Results: There were no significant differences in the patient characteristics between the two groups. Platelet count on postoperative day (POD) 5 and WBC count on POD 3 were significantly higher in the DPS group, and these differences continued to be significant until the 3rd month after surgery. Serum hemoglobin and hematocrit in the 1st month after surgery were also significantly higher in the SpDP with PSAV group. Conclusion: The hematological benefits of SpDP with PSAV include reduction of postoperative hematological abnormalities in the early postoperative phase and recovery of the serum hemoglobin and hematocrit levels in the early postoperative phase.
Comparison of the Effects of Pioglitazone versus Placebo when Given in Addition to Standard Insulin Treatment in Patients with Type 2 Diabetes Mellitus Requiring Hemodialysis: Results from the PIOren Study
Authors: Galle Jan , Kleophas Werner , Dellanna Frank , Schmid Volkmar H.R. , Forkel Claudia , Dikta Gerhard , Krajewski Vera , Fuchs Winfried , Forst Thomas , Pfützner Andreas
Published: May 2012

Background: Patients with type 2 diabetes mellitus and advanced kidney disease are usually treated with insulin. However, the prolonged pharmacokinetic insulin profile in patients with delayed renal insulin elimination impairs a successful therapy. Due to its hepatic metabolism, pioglitazone is a potential candidate for additional administration. The aim of this study was to investigate the effect of pioglitazone versus placebo on total daily insulin requirements and several pleiotropic factors in type 2 diabetes patients requiring hemodialysis. Methods: The effect of pioglitazone (30 mg) versus placebo was explored in this prospective, randomized, double-blind parallel multicenter phase II study analyzing data from 36 patients with type 2 diabetes mellitus currently under hemodialysis (25 male, 11 female, aged 69.2 ± 7.9 years, baseline HbA1c 7.6 ± 0.9%). The most important efficacy parameters collected before dialysis and after an overnight fast at baseline and after 6 months were: total daily insulin dose, HbA1c, fasting blood glucose, adiponectin, HDL, LDL, triglycerides, NT-proBNP, and ultrafiltrate volume. Results: Application of pioglitazone resulted in a significant decrease of the daily insulin dose by 35% versus baseline (placebo: –10%, n.s.), improvement in HbA1c (–0.60 ± 0.87%, p = 0.015; placebo: 0.21 ± 1.1%, n.s.) and adiponectin (7.33 ± 4.80 mg/l, p < 0.001; placebo: –1.37 ± 2.56 mg/l, n.s.). Slight improvements or no changes were seen with fasting glucose, triglycerides, HDL, LDL and NT-proBNP. There was no indication of increased hypoglycemia risk and volume overload by the addition of pioglitazone. Conclusions: Addition of pioglitazone to insulin in patients with late-stage kidney failure requiring hemodialysis is a well-tolerated treatment option that improves glycemic control with simultaneous insulin-sparing potential.
Functional Transcranial Doppler: Presymptomatic Changes in Fabry Disease
Authors: Azevedo Elsa , Mendes Amélia , Seixas Daniela , Santos Rosa , Castro Pedro , Ayres-Basto Margarida , Rosengarten Bernhard , Oliveira João Paulo
Published: May 2012

Background and Aim: Cerebrovascular disease may progress asymptomatically in the early stages of Fabry disease (FD). Our aim was to test whether functional transcranial Doppler (fTCD) could provide useful data in the evaluation of these presymptomatic FD patients. Methods: A cohort of 12 adult FD patients from families with the classical phenotype of the disease was evaluated with fTCD in the posterior cerebral artery. Results: Compared to healthy controls, resting blood velocities were significantly lower in the FD cohort (p = 0.032 for systolic, p = 0.021 for diastolic). FTCD suggested a disturbed neurovascular coupling in the visual cortex of FD patients, with lower gain (p = 0.007) and rate time (p = 0.019). Men had a significantly higher attenuation (p = 0.013) and lower natural frequency (p = 0.046) than the heterozygous women. Conclusion: These data are the first to suggest that patients with FD may develop cortical vascular dysfunction in the territory of the posterior circulation, early in the natural history of the disease. If the present findings are confirmed in larger, prospective studies, fTCD will be useful for assessing stroke risk in as yet asymptomatic FD patients, improving preventive therapeutic management.
Pleural Effusion in Lung Cancer: More Questions than Answers
Authors: Froudarakis Marios E.
Published: May 2012

Lung cancer remains the most common fatal malignancy, despite more aggressive therapies. Few patients will survive 5 years, as up to 80% of the patients will present with advanced-stage disease at diagnosis. Chemotherapy offers little benefit in terms of median survival and disease-free survival in patients with advanced-stage non-small-cell lung carcinoma (NSCLC). In the last decade, the development of new targeted therapies based on the better understanding of different paths of carcinogenesis has given new hope to both physicians and patients. Metastatic pleural effusion from lung cancer has a particularly poor prognosis, and in NSCLC it is actually reclassified as stage IV disease. A possible explanation of this observation is differences in the genomics between primary tumors and metastasis, leading to possible different therapeutic approaches with novel molecular therapies in this patient population. The current review aims to summarize the actual situation of research in pleural disease due to lung carcinoma in relation to novel targeted therapies tested in this patient population.
Hematopoietic Interferon Regulatory Factor 8-Deficiency Accelerates Atherosclerosis in Mice
Authors: Döring Yvonne , Soehnlein Oliver , Drechsler Maik , Shagdarsuren Erdenechimeg , Chaudhari Sweena M. , Meiler Svenja , Hartwig Helene , Hristov Mihail , Koenen Rory R. , Hieronymus Thomas , Zenke Martin , Weber Christian , Zernecke Alma
Published: May 2012

Objective—

Inflammatory leukocyte accumulation drives atherosclerosis. Although monocytes/macrophages and polymorphonuclear neutrophilic leukocytes (PMN) contribute to lesion formation, sequelae of myeloproliferative disease remain to be elucidated.

Methods and Results—

We used mice deficient in interferon regulatory factor 8 (IRF8
−/−
) in hematopoietic cells that develop a chronic myelogenous leukemia-like phenotype. Apolipoprotein E-deficient mice reconstituted with IRF8
−/−
or IRF8
−/−
apolipoprotein E-deficient bone marrow displayed an exacerbated atherosclerotic lesion formation compared with controls. The chronic myelogenous leukemia-like phenotype in mice with IRF8
−/−
bone marrow, reflected by an expansion of PMN in the circulation, was associated with an increased lesional accumulation and apoptosis of PMN, and enlarged necrotic cores. IRF8
−/−
compared with IRF8
+/+
PMN displayed unaffected reactive oxygen species formation and discharge of PMN granule components. In contrast, accumulating in equal numbers at sites of inflammation, IRF8
−/−
macrophages were defective in efferocytosis, lipid uptake, and interleukin-10 cytokine production. Importantly, depletion of PMN in low-density lipoprotein receptor or apolipoprotein E-deficient mice with IRF8
−/−
or IRF8
−/−
apolipoprotein E-deficient bone marrow abrogated increased lesion formation.

Conclusion—

These findings indicate that a chronic myelogenous leukemia-like phenotype contributes to accelerated atherosclerosis in mice. Among proatherosclerotic effects of other cell types, this, in part, is linked to an expansion of functionally intact PMN.
Macrophage-Derived Angiopoietin-Like Protein 2 Accelerates Development of Abdominal Aortic Aneurysm
Authors: Tazume Hirokazu , Miyata Keishi , Tian Zhe , Endo Motoyoshi , Horiguchi Haruki , Takahashi Otowa , Horio Eiji , Tsukano Hiroto , Kadomatsu Tsuyoshi , Nakashima Yukiko , Kunitomo Ryuji , Kaneko Yasushi , Moriyama Shuji , Sakaguchi Hisashi , Okamoto Ken , Hara Masahiko , Yoshinaga Takashi , Yoshimura Koichi , Aoki Hiroki , Araki Kimi , Hao Hiroyuki , Kawasuji Michio , Oike Yuichi
Published: May 2012

Objective—

Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA).

Methods and Results—

Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl
2
-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2.

Conclusion—

Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy.
Serum-Glucocorticoid Regulated Kinase 1 Regulates Alternatively Activated Macrophage Polarization Contributing to Angiotensin II–Induced Inflammation and Cardiac Fibrosis
Authors: Yang Min , Zheng Jiao , Miao Yanjv , Wang Ying , Cui Wei , Guo Jun , Qiu Shulan , Han Yalei , Jia Lixin , Li Huihua , Cheng Jizhong , Du Jie
Published: May 2012

Objective—

Inflammatory responses play a pivotal role in the pathogenesis of hypertensive cardiac remodeling. Macrophage recruitment and polarization contribute to the development of cardiac fibrosis. Although serum-glucocorticoid regulated kinase 1 (SGK1) is a key mediator of fibrosis, its role in regulating macrophage function leading to cardiac fibrosis has not been investigated. We aimed to determine the mechanism by which SGK1 regulates the cardiac inflammatory process, thus contributing to hypertensive cardiac fibrosis.

Methods and Results—

After angiotensin II infusion in mice, cardiac hypertrophy and fibrosis developed in wild-type but not SGK1 knockout mice, with equal levels of hypertension in both groups. Compared with wild-type hearts, SGK1 knockout hearts showed less infiltration of leukocytes and macrophages. Importantly, SGK1 deficiency led to decreased proportion of alternatively activated (M2) macrophages and increased levels of profibrotic cytokines. Angiotensin II infusion induced phosphorylation and nuclear localization of signal transducer and activator of transcription 3 (STAT3) whereas SGK1 knockout hearts showed this effect attenuated. In a 3-dimensional peptide gel culture, inhibition of STAT3 suppressed differentiation into M2 macrophages. Coculture of macrophages with cardiac fibroblasts in 3-dimensional peptide gel stimulated the expression of α-smooth muscle actin and collagen in cardiac fibroblasts. However, SGK1 knockout mice with macrophage deficiency showed reduced fibroblast-to-myofibroblast transition.

Conclusion—

SGK1 may play an important role in macrophage recruitment and M2 macrophage activation by activating the STAT3 pathway, which leads to angiotensin II–induced cardiac fibrosis.
Interleukin-12p35 Deletion Promotes CD4 T-Cell–Dependent Macrophage Differentiation and Enhances Angiotensin II–Induced Cardiac Fibrosis
Authors: Li Yulin , Zhang Congcong , Wu Yina , Han Yalei , Cui Wei , Jia Lixin , Cai Lun , Cheng Jizhong , Li Huihua , Du Jie
Published: May 2012

Objective—

Interleukin-12 is essential for the differentiation of naïve T cells into interferon-γ–producing T cells, which regulate inflammatory responses. We investigated this process of regulating hypertension-induced cardiac fibrosis.

Methods and Results—

Mice infused with angiotensin II showed a marked increase in interleukin-12p35 expression in cardiac macrophages. The degree of cardiac fibrosis was significantly enhanced in interleukin-12p35 knockout (p35-KO) mice compared with wild-type (WT) littermates in response to angiotensin II. Fibrotic hearts of p35-KO mice showed increased accumulation of alternatively activated (M2) macrophages and expression of M2 genes such as Arg-1 and Fizz1. Bone marrow–derived macrophages from WT or p35-KO mice did not differ in differentiation in response to angiotensin II treatment; however, in the presence of CD4
+
T cells, macrophages from p35-KO mice differentiated into M2 macrophages and showed elevated expression of transforming growth factor-β. Moreover, CD4
+
T-cell–treated p35-KO macrophages could stimulate cardiac fibroblasts to differentiate into α-smooth muscle actin–positive and collagen I–positive myofibroblasts in 3-dimensional nanofiber gels. Neutralizing antibodies against transforming growth factor-β inhibited myofibroblast formation induced by M2 macrophages.

Conclusion—

Deficiency in interleukin-12p35 regulates angiotensin II–induced cardiac fibrosis by promoting CD4
+
T-cell–dependent differentiation of M2 macrophages and production of transforming growth factor-β.
Stearic Acid Accumulation in Macrophages Induces Toll-Like Receptor 4/2-Independent Inflammation Leading to Endoplasmic Reticulum Stress–Mediated Apoptosis
Authors: Anderson Emily K. , Hill Andrea A. , Hasty Alyssa H.
Published: May 2012

Objective—

Elevated serum free fatty acid levels are associated with an increased risk of cardiovascular disease and type 2 diabetes mellitus. Macrophages are recruited to atherosclerotic plaques and metabolic tissues during obesity and accumulate lipids, including free fatty acids. We investigated the molecular consequences of intracellular saturated free fatty acid accumulation in macrophages.

Methods and Results—

Previously, we demonstrated that cotreatment of mouse peritoneal macrophages (MPMs) with stearic acid and triacsin C (an inhibitor of long-chain acyl coenzyme A synthetases) results in intracellular free fatty acid accumulation and apoptosis. Here, we used Western blotting analysis, real-time reverse transcription polymerase chain reaction, and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining to assess endoplasmic reticulum (ER) stress, inflammation, and apoptosis in MPMs. Intracellular stearic acid accumulation induces Toll-like receptor 4/2-independent inflammation that results in ER stress–mediated apoptosis of MPMs. Polarization of MPMs to a proinflammatory M1 phenotype increases their susceptibility to inflammation and ER stress, but not apoptosis, in response to cotreatment with stearic acid and triacsin C.

Conclusion—

Intracellular accumulation of stearic acid in MPMs activates inflammatory signaling, leading to ER stress–mediated apoptosis. M1 macrophages are more prone to stearic acid–induced inflammation and ER stress. These same pathways may be activated in macrophages residing in atherosclerotic plaques and metabolic tissues during conditions of obesity and hyperlipidemia.
Isolated Rabbit Working Heart Function During Progressive Inhibition of Myocardial SERCA Activity
Authors: Elliott Elspeth B. , Kelly Allen , Smith Godfrey L. , Loughrey Christopher M.
Published: May 2012

Rationale:

The extent to which sarcoplasmic reticulum Ca
2+
ATPase (SERCA) activity alone determines left ventricular (LV) pump function is unknown.

Objective:

To correlate SERCA activity with hemodynamic function of rabbit LV during thapsigargin perfusion.

Methods and Results:

Isolated rabbit hearts were perfused in working heart configuration, and LV pump function was assessed using a pressure-volume catheter. Rapid and complete (>95%) inhibition of SERCA was associated with a moderate decrease in cardiac function (to 70%–85% of control). Further decrease in cardiac function to 50%–75% of control occurred over the next ≈30 minutes despite no detectable further inhibition of SERCA activity. Analysis of the 20 seconds prior to pump failure revealed a rapid decrease in end diastolic volume. Intermediate levels of SERCA function (≈50% of control) had only minor hemodynamic effects. Parallel experiments in field-stimulated isolated ventricular cardiomyocytes monitored intracellular Ca
2+
and cell shortening. On perfusion with thapsigargin, Ca
2+
transient amplitude and cell shortening fell to ≈70% of control followed by increased diastolic Ca
2+
concentration and diastolic cell shortening to achieve a new steady state.

Conclusions:

The relationship between SERCA activity and LV function in the rabbit is highly nonlinear. In the short term, only moderate effects on LV pump function were observed despite almost complete (>95%) reduction in SERCA activity. The terminal decline of function was associated with sudden sustained increase in diastolic tone comparable to the sustained contraction observed in isolated cardiomyocytes. Secondary increases of intracellular Ca
2+
and Na
+
following complete SERCA inhibition eventually limit contractile function and precipitate LV pump failure.
Platelet-Derived Growth Factor Maintains Stored Calcium Through a Nonclustering Orai1 Mechanism But Evokes Clustering If the Endoplasmic Reticulum Is Stressed by Store Depletion
Authors: McKeown Lynn , Moss Nicholas K. , Turner Paul , Li Jing , Heath Nikki , Burke Dermot , O'Regan David , Gilthorpe Mark S. , Porter Karen E. , Beech David J.
Published: May 2012

Rationale:

Calcium entry through Orai1 channels drives vascular smooth muscle cell migration and neointimal hyperplasia. The channels are activated by the important growth factor platelet-derived growth factor (PDGF). Channel activation is suggested to depend on store depletion, which redistributes and clusters stromal interaction molecule 1 (STIM1), which then coclusters and activates Orai1.

Objective:

To determine the relevance of STIM1 and Orai1 redistribution in PDGF responses.

Methods and Results:

Vascular smooth muscle cells were cultured from human saphenous vein. STIM1 and Orai1 were tagged with green and red fluorescent proteins to track them in live cells. Under basal conditions, the proteins were mobile but mostly independent of each other. Inhibition of sarco-endoplasmic reticulum calcium ATPase led to store depletion and dramatic redistribution of STIM1 and Orai1 into coclusters. PDGF did not evoke redistribution, even though it caused calcium release and Orai1-mediated calcium entry in the same time period. After chemical blockade of Orai1-mediated calcium entry, however, PDGF caused redistribution. Similarly, mutagenic disruption of calcium flux through Orai1 caused PDGF to evoke redistribution, showing that calcium flux through the wild-type channels had been filling the stores. Acidification of the extracellular medium to pH 6.4 caused inhibition of Orai1-mediated calcium entry and conferred capability for PDGF to evoke complete redistribution and coclustering.

Conclusions:

The data suggest that PDGF has a nonclustering mechanism by which to activate Orai1 channels and maintain calcium stores replete. Redistribution and clustering become important, however, when the endoplasmic reticulum stress signal of store depletion arises, for example when acidosis inhibits Orai1 channels.
Increased Intestinal Lipid Absorption Caused by Ire1β Deficiency Contributes to Hyperlipidemia and Atherosclerosis in Apolipoprotein E–Deficient Mice
Authors: Iqbal Jahangir , Queiroz Joyce , Li Yan , Jiang Xian-Cheng , Ron David , Hussain M. Mahmood
Published: May 2012

Rationale:

High fasting serum lipid levels are significant risk factors for atherosclerosis. However, the contributions of postprandial excursions in serum lipoproteins to atherogenesis are less well-characterized.

Objective:

This study aims to delineate whether changes in intestinal lipid absorption associated with loss of inositol-requiring enzyme 1β (Ire1β) would affect the development of hyperlipidemia and atherosclerosis in
Apoe
−/−
mice.

Methods and Results:

We used Ire1β-deficient mice to assess the contribution of intestinal lipid absorption to atherosclerosis. Here, we show that
Ire1b
−/−
/Apoe
−/−
mice contain higher levels of intestinal microsomal triglyceride transfer protein, absorb more lipids, exhibit hyperlipidemia, and have higher levels of atherosclerotic plaques compared with
Apoe
−/−
mice when fed chow and western diets.

Conclusions:

These studies indicate that Ire1β regulates intestinal lipid absorption and that increased intestinal lipoprotein production contributes to atherosclerosis.
Poor Prognosis in Warfarin-Associated Intracranial Hemorrhage Despite Anticoagulation Reversal
Authors: Dowlatshahi Dar , Butcher Kenneth S. , Asdaghi Negar , Nahirniak Susan , Bernbaum Manya L. , Giulivi Antonio , Wasserman Jason K. , Poon Man-Chiu , Coutts Shelagh B.
Published: May 2012

Background and Purpose

Anticoagulant-associated intracranial hemorrhage (aaICH) presents with larger hematoma volumes, higher risk of hematoma expansion, and worse outcome than spontaneous intracranial hemorrhage. Prothrombin complex concentrates (PCCs) are indicated for urgent reversal of anticoagulation after aaICH. Given the lack of randomized controlled trial evidence of efficacy, and the potential for thrombotic complications, we aimed to determine outcomes in patients with aaICH treated with PCC.

Methods

We conducted a prospective multicenter registry of patients treated with PCC for aaICH in Canada. Patients were identified by local blood banks after the release of PCC. A chart review abstracted clinical, imaging, and laboratory data, including thrombotic events after therapy. Hematoma volumes were measured on brain CT scans and primary outcomes were modified Rankin Scale at discharge and in-hospital mortality.

Results

Between 2008 and 2010, 141 patients received PCC for aaICH (71 intraparenchymal hemorrhages). The median age was 78 years (interquartile range, 14), 59.6% were male, and median Glasgow Coma Scale was 14. Median international normalized ratio was 2.6 (interquartile range, 2.0) and median parenchymal hematoma volume was 15.8 mL (interquartile range, 31.8). Median post-PCC therapy international normalized ratio was 1.4: 79.5% of patients had international normalized ratio correction (<1.5) within 1 hour of PCC therapy. Patients with intraparenchymal hemorrhage had an in-hospital mortality rate of 42.3% with median modified Rankin Scale of 5. Significant hematoma expansion occurred in 45.5%. There were 3 confirmed thrombotic complications within 7 days of PCC therapy.

Conclusions

PCC therapy rapidly corrected international normalized ratio in the majority of patients, yet mortality and morbidity rates remained high. Rapid international normalized ratio correction alone may not be sufficient to alter prognosis after aaICH.
Clopidogrel Load for Emboli Reduction in Patients With Symptomatic Carotid Stenosis Undergoing Urgent Carotid Endarterectomy
Authors: Tsivgoulis Georgios , Kerasnoudis Antonios , Krogias Christos , Vadikolias Konstantinos , Meves Saskia H. , Heliopoulos Ioannis , Georgakarakos Efstratios , Piperidou Charitomeni , Alexandrov Andrei V.
Published: May 2012

Background and Purpose—

Microembolic signals (MES) on transcranial Doppler are an independent risk factor for recurrent stroke in patients with extracranial symptomatic/asymptomatic carotid artery stenosis (CARAS). Clopidogrel load (300 mg) combined with dual antiplatelet therapy has been shown to reduce MES in patients with symptomatic CARAS. We sought to determine feasibility of clopidogrel load in decreasing asymptomatic embolization in patients with symptomatic CARAS undergoing urgent carotid endarterectomy within the first 2 weeks from the index event.

Subjects and Methods—

Consecutive patients with symptomatic CARAS (70%–99%) and presence of MES on 1-hour baseline (<24 hours from the index event) transcranial Doppler monitoring of ipsilateral middle cerebral artery were treated with clopidogrel load followed by clopidogrel (75 mg)±aspirin (100 mg) during the elapsed time period between hospital admission and urgent carotid endarterectomy at 3 tertiary-care stroke centers. Repeat 1-hour transcranial Doppler monitoring was performed the day before surgery. Bleeding complications during surgery and recurrent strokes or transient ischemic attacks during the first month of ictus were prospectively recorded.

Results—

A total of 11 symptomatic CARAS patients (mean age, 66±7 years; 73% men; 64% acute ischemic strokes) were treated with clopidogrel load followed by dual (67%) or single (33%) antiplatelet therapy. MES count was significantly reduced between baseline (median count, 8 MES/h; interquartile range, 6–19) and repeat transcranial Doppler monitoring (0 MES/h; interquartile range, 0–3;
P
=0.003). No bleeding complications, recurrent strokes, or transient ischemic attacks were documented.

Conclusions—

Our pilot observational study provides preliminary nonrandomized data regarding the potential efficacy of clopidogrel load to reduce asymptomatic embolization in patients with symptomatic CARAS before urgent carotid endarterectomy.
Fabrication of TiC and ZrC reinforced Al-4 wt%Cu composite droplets using impulse atomization
Authors: Kaftelen Hülya , Henein Hani , Öveçoğlu M Lütfi
Published: May 2012

In this study, Al-4 wt%Cu alloy and its composites reinforced with different initial particle sizes of ZrC (8 µm and 157 µm) and TiC (13 µm and 93 µm) were fabricated by impulse atomization, and the microstructure of composite and unreinforced alloy droplets were examined by scanning electron microscopy, x-ray diffraction and cell size analyses. Scanning electron microscopic observations of composite droplets indicated that fine ZrC particles (8 µm) were mostly clustered while the other composites of the present investigation were distributed rather uniformly within the fine microstructure of droplets. The relationship between the cell size and the amount of carbide particles reveals that the presence of carbide particles in the alloy powders yields a finer structure. This could be due to the role of the carbide particles as heterogeneous sites for nucleation and to some extent due to particle restricted growth of matrix cells during solidification.
Processing and properties of SiCp/Fe composites by resistance sintering with a novel dynamic temperature control
Authors: Zhuang Weibin , Zong BY , Wang Yaomian , Yang Yufang
Published: May 2012

A two-stage resistance sintering with novel dynamic temperature control technology has been developed to manufacture SiCp/Fe composites. Principles of the technology and equipment were examined and reported in comparison with hot pressing and conventional resistance sintering. The composites with different reinforcement volume fractions and sizes were processed by the new technology to investigate effects of reinforcement features on hardness, yield stress and wear resistance. The experimental results demonstrate that the SiCp/Fe composites in nearly full density can be realized within a few minutes by the technology, and the yield stress and Vickers hardness of the 10 vol.% SiCp/Fe composite were achieved up to the remarkable values of 949 MPa and 501HV5, respectively. It is shown that the composite with 10 vol.% SiC and particle size of 13 µm has the best mechanical properties among the composites in ranges of the volume fraction from 5% to 15% and of the particle size from 3 to 45 µm, respectively. Modeling by the Eshelby approach based on strengthening mechanism of load sharing was carried out to interpret the experimental results.
Strength prediction of composite π joint under bending load and study of geometric and material variations effects
Authors: Fu Yue , Zhang Jianyu , Zhao Libin
Published: May 2012

This article concentrates on the design of composite π joint, which is an effective connector for integrated composite structures in aerospace structures. A brief review of research on out-of-plane joints is first presented to current practice towards the design of such π joints. Progressive damage models are established to trace failure analysis from damage onset to ultimate collapse of joints, which highlight the failure mechanism and internal mechanical behaviours. Four kinds of failure criteria are used firstly, and after comparing the numerical prediction results with the experimental results, one failure criterion is chosen for the simulation of this joint. Influences of structural and geometric parameters such as structural configuration, overlaminate material, ply angle, fillet radius and upstanding/horizontal leg length of overlaminate on flexural resistance ability are studied to provide ‘optimal’ design schemes. Moment–displacement graphs from the mechanical experiments are presented and physical failure phenomena of the joint under bending load are depicted. The good agreement between the predictions and experimental results gives evidence of the efficiency of numerical analysis.
Fabrication of carbon nanotubes dispersed woven carbon fiber/epoxy composites and their damping characteristics
Authors: Kim Hee Chul , Kim Eun Ho , Lee In , Byun Joon Hyung , Kim Byung Sun , Ahn Seok Min
Published: May 2012

Damping characteristics of carbon nanotubes dispersed woven carbon fiber/epoxy composites were investigated. The composites were fabricated by an advanced resin film infusion prepreg manufacturing process based on the calendaring process using three-roll mill. Through this advanced process, well-dispersed nanocomposites containing high weight percent (up to 7 wt%) of carbon nanotubes was achieved. It was confirmed through the scanning electron microscopic images of the carbon nanotubes dispersed composites. Damping characteristics of the specimen were measured by the impact vibration test of the composites beam specimens. Considerable improvement of damping characteristics was observed in the carbon nanotubes dispersed composites, and structural damping increased as the weight percent of carbon nanotubes was increased. Damping ratio was improved up to 12.3% (at the 1st natural frequency) and 16.1% (at the 2nd natural frequency), especially in the 7 wt% carbon nanotubes dispersed specimen. Tensile test was performed to investigate the effects of carbon nanotubes on the tensile properties. The tensile stiffness of carbon nanotubes dispersed composites was similar with the conventional composites; however, tensile strength was degraded.
Moderation Effects of Power Distance on the Relationship Between Types of Empowerment and Employee Satisfaction
Authors: Fock Henry , Hui Michael K. , Au Kevin , Bond Michael Harris
Published: May 2012

Previous research concludes that empowerment is ineffective with employees from societies high in power distance. The present study examines this conclusion across three types of empowerment: discretion empowerment, psychological empowerment, and leadership empowerment (or empowerment leadership behaviors). To assess the effects of power distance on these three types of empowerment, employee surveys were conducted in Canada (a society low in power distance) and in China (a society high in power distance). Results showed that the effect of discretion empowerment on employee satisfaction was less pronounced in China, just as previous literature had concluded about the dynamics of societies high in power distance. However, the effect of the leadership empowerment on employee satisfaction via the competence facet of psychological empowerment was found to be more pronounced in Canada, a society lower in power distance. These conclusions at the cultural level were also confirmed at the psychological level. We thus advocate that empowerment remains an advantageous strategy to organizations in both societies and individuals high and low in power distance, depending on the type of empowerment involved.
Drinking, Socioemotional Functioning, and Academic Progress in Secondary School
Authors: Crosnoe Robert , Benner Aprile D. , Schneider Barbara
Published: May 2012

Secondary schools are sites of academic instruction but also contexts of socioemotional development, and the intertwining of these two functions has consequences for adolescents’ future health and education. Drawing on nationally representative data from the National Longitudinal Study of Adolescent Health ( n = 8,271), this study explored the bidirectional associations among indicators of adolescents’ alcohol use and their feelings of social integration at school. Socioemotional problems did not predict increased drinking over time, but drinking predicted declining socioemotional functioning, with negative implications for adolescents’ academic grades by the end of high school. These associations, however, were conditioned by aspects of school context, with drinkers feeling more marginalized in schools characterized by dense networks with low rates of drinking.
A Realistic Look at STEM and the Role of Community Colleges
Authors: Hagedorn Linda Serra , Purnamasari Agustina Veny
Published: May 2012

American policy makers, educators, and others are concerned that predicted workforce shortages in science, technology, engineering, and mathematics (STEM) fields will have a catastrophic impact on the economy. This article takes a realistic look at the “STEM problem,” identifying how community colleges can be a part of the solution. We provide evidence that shortages in STEM workers vary by geographic locale. Furthermore, STEM achievement is not consistent across ethnic groups or between men and women. These gaps may be due to unequal access to STEM degree programs and the shortage of quality STEM teachers.
An Ethical Decision-Making Framework for Community College Administrators
Authors: Oliver Diane E. , Hioco Barbara
Published: May 2012

This article provides community college administrators, as well as university faculty members who teach doctoral and master’s courses in community college leadership, with a framework that facilitates ethical decision making. Administrators’ decisions must be grounded in critical thinking that includes ethical considerations.
Trouble in Smogville
Authors: Temby Owen
Published: May 2012

By the mid-1950s the rapidly growing Toronto was arguably North America’s third-worst smog-stricken city. Its downtown waterfront area, referred to by the local media as “Smogville,” was home to a range of pollution sources, many of which were exempt from regulation by the city. At issue politically was whether the authority to regulate polluting sources would stay with Metropolitan Toronto or be handed to the Ontario government and whether the former would be able to regulate the exempt sources (in particular, trains, ships, and various types of manufacturers). By the end of the decade, Metropolitan Toronto still governed the pollution sources within its borders, but with substantially expanded authority to do so. This article provides an account of the politics of the city’s early attempt at air pollution governance, focusing on the role played by Toronto’s real estate interests in lobbying for air pollution relief.