bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Prothrombin Complex Concentrate and Recombinant Activated Factor VII to Reverse Rivaroxaban in a Rabbit Model
Authors: Godier Anne , Miclot Anastasia , Le Bonniec Bernard , Durand Marion , Fischer Anne-Marie , Emmerich Joseph , Marchand-Leroux Catherine , Lecompte Thomas , Samama Charles-Marc
Published: October 2011

Background

As a potent anticoagulant agent, rivaroxaban exposes a risk of bleeding. An effective way to reverse its effects is needed. Objectives were to study efficacy and safety of recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of an overdose of rivaroxaban in a rabbit model of bleeding and thrombosis.

Methods

First, a dose-ranging study assessed the minimal rivaroxaban dose that increased bleeding. Then, 48 anesthetized and ventilated rabbits were randomized into four groups: control (saline), rivaroxaban (rivaroxaban and saline), rFVIIa (rivaroxaban and rFVIIa), and PCC (rivaroxaban and PCC). The Folts model was applied: a stenosis and an injury were carried out on the carotid artery, inducing thrombosis, detected as cyclic flow reductions, which were recorded over 20 min. Then the following were measured: ear immersion bleeding time, clotting times, anti-Xa activity, thrombelastometric parameters, and thrombin generation test. Ultimately, a hepatosplenic section was performed and the total amount of blood loss after 15 min was evaluated as primary endpoint.

Results

Rivaroxaban increased blood loss (17 g [8-32] vs. 7 g [5-18] for control (median [range]), P = 0.0004), ear bleeding time, clotting times, thrombelastographic clotting time, and decreased thrombin generation. In contrast, rFVIIa decreased ear bleeding time (92 s [65-115] vs. 140 s [75-190], P < 0.02), but without efficacy on blood loss. PCC and rFVIIa decreased activated partial thromboplastin time as well as thrombelastographic clotting time. Regarding safety, neither rFVIIa nor PCC increased cyclic flow reductions.

Conclusion

rFVIIa and PCC partially improved laboratory parameters, but did not reverse rivaroxaban induced-bleeding.
Relationship between Bispectral Index Values and Volatile Anesthetic Concentrations during the Maintenance Phase of Anesthesia in the B-Unaware Trial
Authors: Whitlock Elizabeth L. , Villafranca Alexander J. , Lin Nan , Palanca Ben J. , Jacobsohn Eric , Finkel Kevin J. , Zhang Lini , Burnside Beth A. , Kaiser Heiko A. , Evers Alex S. , Avidan Michael S.
Published: October 2011

Background

Hypnotic depth during anesthesia affects electroencephalography waveforms and electroencephalogram-derived indices, such as the bispectral index (BIS). Titrating anesthetic administration against the BIS assumes reliable relationships between BIS values, electroencephalogram waveforms, and effect site concentration, beyond loss of responsiveness. Associations among BIS, end-tidal anesthetic concentrations (ETAC), and patient characteristics were examined during anesthetic maintenance, using B-Unaware trial data.

Methods

Pharmacokinetically stable ETAC epochs during intraoperative anesthetic maintenance were analyzed. A generalized estimating equation determined independent relationships among BIS, ETAC (in age-adjusted minimum alveolar concentration equivalents), patient characteristics, and 1-yr mortality. Further individual and population characteristics were explored graphically.

Results

A total of 3,347,523 data points from 1,100 patients were analyzed over an ETAC range from 0.42 to 1.51 age-adjusted minimum alveolar concentration. A generalized estimating equation yielded a best predictive equation: BIS = 62.9-1.6 (if age younger than 60 yr) -1.6 (if female) -2.5 (if American Society of Anesthesiologists physical status more than 3) -2.6 (if deceased at 1 yr) -2.5 (if N2O was not used) -1.4 (if midazolam dose more than 2 mg) -1.3 (if opioid dose more than 50 morphine equivalents) -15.4 × age-adjusted minimum alveolar concentration. Although a population relationship between ETAC and BIS was apparent, interindividual variability in the strength and reliability of this relationship was large. Decreases in BIS with increasing ETAC were not reliably observed. Individual-patient linear regression yielded a median slope of -8 BIS/1 age-adjusted minimum alveolar concentration (interquartile range -30, 0) and a median correlation coefficient of -0.16 (interquartile range -0.031, -0.50).

Conclusions

Independent of pharmacokinetic confounding, BIS frequently correlates poorly with ETAC, is often insensitive to clinically significant changes in ETAC, and is vulnerable to interindividual variability. BIS is therefore incapable of finely guiding volatile anesthetic titration during anesthetic maintenance.
Rapid Novel Aortic Arch Replacement for Thoracic Aortic Aneurysm Using Three Continuous Sutures and a Felt Cylindrical Collar
Authors: Watanabe Go , Ohtake Hiroshi , Tomita Shigeyuki
Published: October 2011

This report describes the novel parachute technique of open distal anastomosis at the aortic arch replacement. Two Teflon felt cylindrical collars were initially placed on the anastomotic site of the descending aorta. All four to five outer loops of the stitches used in the parachute technique were tracked by the gathering suture. The anastomotic sutures and three gathering sutures were finally pulled simultaneously. The prosthetic graft and the aortic stump with Teflon felt were safely and completely anastomosed. Surgical or hospital death and serious complications were not found. The mean anastomotic duration (circulatory arrest duration) in 16 patients was 23 minutes. Our novel technique using a Teflon felt cylindrical collar and modified continuous suturing was not only safe but also reduced the duration of anastomosis and minimized blood loss. This technique is simple and can be applied to aortic valve replacement.
Single-Institution Experience on Robot-Assisted Thoracoscopic Operations for Mediastinal Diseases
Authors: Rea Federico , Schiavon Marco , Di Chiara Francesco , Marulli Giuseppe
Published: October 2011

Objective

After the introduction of video-assisted thoracoscopic surgery 20 years ago, the minimally invasive techniques in thoracic surgery have found a growing application. The recent introduction of robotic technology has increased the potentiality of thoracoscopic technique leading to an expansion of indications and applications, particularly for the management of mediastinal diseases. We reviewed our experience in robot-assisted thoracoscopic resection of benign and malignant mediastinal diseases.

Methods

Between 2002 and 2010, 108 patients (79 women and 29 men; median age 38 y) underwent robot-assisted thoracoscopy using the “da Vinci” robotic system for several mediastinal diseases. There were 100 thymectomies, 3 resections of paravertebral tumors, 1 thymic cyst, 1 ectopic goitre, 1 ectopic mediastinal parathyroidectomy, 1 thymic carcinoid, and 1 foregut cyst. Ninety-five (87.9%) patients were affected by myasthenia gravis.

Results

All procedures were completed successfully using the da Vinci robot; no open conversions were required, but in three (2.8%) cases, a fourth access was added. There was no surgical mortality; four (3.6%) patients had postoperative complications (two hemothorax, one chylothorax, and one fever) treated conservatively. Median operation time was 120 (range 60–300) minutes and median hospitalization was 3 (range 2–14) days. Global benefit rate for patients with myasthenia gravis reached the value of 93.4% with progressive improvement over years.

Conclusions

Several mediastinal operations may be feasible by using a robot-aided thoracoscopic approach. The technical innovations offered by robotic instrumentation make all procedures safer and easier when compared with standard thoracoscopic approach, with particular reference for application in mediastinal field.
Minimally Invasive Ivor Lewis Esophagectomy after Induction Therapy Yields Similar Early Outcomes to Surgery Alone
Authors: Tapias Luis F. , Morse Christopher R.
Published: October 2011

Objective

Although considered an integral part of treatment for regionally advanced esophageal cancer, there is conflicting literature regarding the effect of neoadjuvant chemoradiotherapy on esophagectomy. The objectives of this study are to examine the effect of neoadjuvant therapy in regard to perioperative parameters, morbidity, and short-term mortality in patients undergoing a minimally invasive Ivor Lewis esophagectomy (MIE).

Methods

This is a retrospective review of 39 patients undergoing MIE for esophageal cancer during 2007–2010.

Results

Of the 39 patients, 14 (36%) did not receive neoadjuvant therapy (NCR) and 25 (64%) did receive either chemoradiotherapy or chemotherapy (CR). On comparing NCR vs CR, there was no difference in operative time (361 vs 362 minutes; P = 0.94) or estimated blood loss (233 vs 190 mL; P = 0.06). All patients underwent an R0 resection, and there was no difference in the mean number of lymph nodes harvested (NCR 21.5 vs CR 21.6; P = 0.95). Both groups had mean intensive care unit stay of 1 day (P = 0.7), and there was no difference in length of stay (NCR 7.4 vs CR 8.2 days; P = 0.38). There were no deaths or anastomotic leaks in either group. The incidence of complications in the NCR group was 21% (3/14) while in the CR group was 48% (12/25). Complications were not associated with neoadjuvant therapy [CR vs NCR: odds ratio = 3.44 (0.72–16.38); P = 0.121], even after adjusting for comorbidities and age.

Conclusions

MIE can be performed safely following neoadjuvant therapy with similar perioperative results, morbidity, and short-term mortality when compared with MIE alone. Longer follow-up is required for oncologic validity.
Revival of Continuous Suture Technique in Aortic Valve Replacement in Patient with Aortic Valve Stenosis a Novel Modified Technique
Authors: Watanabe Go , Ushijima Teruaki , Tomita Shigeyuki , Yamaguchi Shojiro , Koshida Yoshinao , Iino Kenji
Published: October 2011

Objective

The continuous suture technique has numerous advantages as simple, quick, and effective for aortic valve replacement; however, it is technically difficult. We have modified the continuous suture technique and evaluated our new technique in patients with aortic stenosis.

Methods

Between July 2007 and May 2010, 86 patients with aortic valve stenosis underwent aortic valve replacement alone or with other concomitant cardiac procedures including mitral valve surgery in our hospital. The patients were randomly divided into two groups: group A (n = 43) in which the continuous suture technique with some modifications was used and group B (n = 43) in which the conventional interrupted suture technique was used. There were no statistical differences between two groups in age, sex, body surface area, concomitant cardiac procedures, blood loss, and postoperative extubation time.

Results

The aortic cross-clamp time, cardiopulmonary bypass time, operation time, and hospital stay were significantly shorter in group A than that in group B, and the valve size was significantly larger in group A. No perivalvular leak was detected in postoperative echocardiograms. All patients recovered satisfactorily without complications associated with suture technique or prosthesis. During follow-up of 4 to 38 months, there were no clinically significant complications in group A, while one patient in group B developed perivalvular leakage requiring reoperation 3 months after surgery.

Conclusions

Our modified continuous suture method is useful for aortic valve replacement in patients with aortic stenosis and beneficial for the patients because the procedure is less invasive and a larger valve can be implanted.
The Off-Pump Implantation of an Apicoaortic Valved Graft is Safe and Has No Negative Impact on Coronary Flow and Hemodynamics
Authors: Karapanos Nikolaos Tsirikos , Suddendorf Scott H. , Li Zhuo , Huebner Marianne , Park Soon J. , Joyce Lyle D. , Daly Richard C.
Published: October 2011

Objective

To determine the hemodynamic effect of an off-pump Apicoaortic valved graft (AAVG) implantation, we performed a quantitative coronary flow analysis in a swine model of severe aortic stenosis.

Methods

In 10 swine, cardiac output, coronary flow, right common carotid artery flow, and internal mammary artery flow were measured along with left and right ventricular pressures and aortic and pulmonary artery pressures. A novel AAVG was implanted off-pump on the left ventricular (LV) apex using a specially designed implantation tool and anastomosed to the descending thoracic aorta. Aortic flow was measured proximally and distally of the AAVG-to-descending thoracic aorta anastomosis. After AAVG implantation, epicardial echo confirmed occlusion of the LV outflow tract by a valvuloplasty balloon. Baseline simultaneous measurements of all parameters were repeated after AAVG implantation and intravenous Dobutamine administration.

Results

The AAVG was implanted without any blood loss. After AAVG implantation and LV outflow tract occlusion, the aortic flow proximal to the AAVG-to-descending thoracic aorta anastomosis changed from antegrade (1508 ± 435 mL/min) to retrograde (–529 ± 241 mL/min, P < 0.001). All other measured parameters remained unchanged compared with baseline. After intravenous Dobutamine administration, LV pressure increased from 88 ± 20 to 184 ± 36 mm Hg (+209%, P < 0.0001) and coronary flow increased from 75 ± 34 to 193 ± 90 mL/min (+257%, P = 0.001).

Conclusions

The off-pump implantation of an AAVG is bloodless, safe, reproducible and has no negative impact on coronary flow and hemodynamics. In addition, to the best of our knowledge, this is the first study where blood flow in all coronary arteries was measured simultaneously during an AAVG implantation.
Comparison of the Early Robot-Assisted Lobectomy Experience to Video-Assisted Thoracic Surgery Lobectomy for Lung Cancer a Single-Institution Case Series Matching Study
Authors: Jang Hee-Jin , Lee Hyun-Sung , Park Seong Yong , Zo Jae Ill
Published: October 2011

Objective

Robotic surgery has evolved in urology, gynecology, and general surgery and seems to be an oncologically sound surgical approach. Robotic surgery has been infrequently reported for pulmonary lobectomy. The aim of this study is to compare the outcomes of our early experience in performing robot-assisted lobectomy (RAL) with video-assisted thoracic surgery (VATS) for the treatment of non-small cell lung cancer.

Methods

Between February and October 2009, 40 patients underwent RAL for resectable non-small cell lung cancer. The dissection and anatomic isolation of the hilar structures were performed using two arms of the da Vinci S system. A retrospective comparison with two VATS groups was performed, our initial 40 VATS patients (between January 2006 and February 2007) and our most recent 40 VATS patients (between June 2008 and September 2009). The entire experience with VATS lobectomy is 163 cases.

Results

In the RAL group, the mean age was 64 years, and there were 23 male patients. Adenocarcinoma was diagnosed in 29 patients with a mean tumor size of 3.5 cm. There were no conversions to open thoracotomy. Among the patients in our initial and recent VATS lobectomy groups, the conversion rate was 3 (8%) and 2 (5%) patients, respectively. The operative time for the RAL (240 ± 62 minutes) and the initial VATS lobectomy groups (257 ± 57 minutes) were similar but was longer than the recent VATS lobectomy group (161 ± 39 minutes, P < 0.001). However, the rate of postoperative complications in the RAL group (n = 4, 10%) was significantly lower than that of the initial VATS group (n = 13, 32.5%, P = 0.027) and similar to that of the recent VATS group (n = 7, 17.5%, P = 0.755). Intraoperative bleeding was reduced in the RAL group compared with the initial VATS group (219 mL vs 374 mL P = 0.017), and the median length of postoperative stay was significantly shorter for the RAL group compared with the initial VATS group (6 vs 9 days, P < 0.001).

Conclusions

The outcomes of our early RAL experience was comparable to the our outcomes achieved with VATS lobectomy, whether performed early or late.
Conservation of Plastid Sequences in the Plant Nuclear Genome for Millions of Years Facilitates Endosymbiotic Evolution
Authors: Rousseau-Gueutin Mathieu , Ayliffe Michael A. , Timmis Jeremy N.
Published: October 2011

The nuclear genome of eukaryotes contains large amounts of cytoplasmic organelle DNA (nuclear integrants of organelle DNA [norgs]). The recent sequencing of many mitochondrial and chloroplast genomes has enabled investigation of the potential role of norgs in endosymbiotic evolution. In this article, we describe a new polymerase chain reaction-based method that allows the identification and evolutionary study of recent and older norgs in a range of eukaryotes. We tested this method in the genus Nicotiana and obtained sequences from seven nuclear integrants of plastid DNA (nupts) totaling 25 kb in length. These nupts were estimated to have been transferred 0.033 to 5.81 million years ago. The spectrum of mutations present in the potential protein-coding sequences compared with the noncoding sequences of each nupt revealed that nupts evolve in a nuclear-specific manner and are under neutral evolution. Indels were more frequent in noncoding regions than in potential coding sequences of former chloroplastic DNA, most probably due to the presence of a higher number of homopolymeric sequences. Unexpectedly, some potential protein-coding sequences within the nupts still contained intact open reading frames for up to 5.81 million years. These results suggest that chloroplast genes transferred to the nucleus have in some cases several millions of years to acquire nuclear regulatory elements and become functional. The different factors influencing this time frame and the potential role of nupts in endosymbiotic gene transfer are discussed.
TheLaueUtiltoolkit for Laue photocrystallography. I. Rapid orientation matrix determination for intermediate-size-unit-cell Laue data
Authors: Kalinowski Jarosław A. , Makal Anna , Coppens Philip
Published: October 2011

A new method for determination of the orientation matrix of Laue X-ray data is presented. The method is based on matching of the experimental patterns of central reciprocal lattice rows projected on a unit sphere centered on the origin of the reciprocal lattice with the corresponding pattern of a monochromatic data set on the same material. This technique is applied to the complete data set and thus eliminates problems often encountered when single frames with a limited number of peaks are to be used for orientation matrix determination. Application of the method to a series of Laue data sets on organometallic crystals is described. The corresponding program is available under a Mozilla Public License-like open-source license.
Morphology of epitaxial magnetic alloy nanostructures grown on WSe2(0001) studied by grazing-incidence small-angle X-ray scattering
Authors: Maret Mireille , Liscio Fabiola , Makarov Denys , Simon Jean-Paul , Gauthier Yves , Albrecht Manfred
Published: October 2011

The morphology of epitaxial alloy nanostructures grown on a van der Waals-type WSe2(0001) surface was studied using grazing-incidence small-angle X-ray scattering (GISAXS). Assemblies of 111-oriented islands of (Co,Cr)Pt3and (Co,Fe)Pt alloys were grown at different deposition temperatures, with nominal thicknesses from 0.1 to 3 nm, resulting in various island densities. Evaluation of the GISAXS patterns indicates that for similar growth conditions CrPt3islands are flatter than CoPt or FePt islands and exhibit larger island volumes. These features are correlated with the better wetting behaviour and more negative formation enthalpy of the CrPt3alloy. For dense arrays of self-assembled CoPt islands, much smaller island volumes are extracted from GISAXS experiments than are observed by scanning tunnelling microscope imaging, which indicates that only the upper parts of the islands contribute to the GISAXS signal. Another aspect that needs to be taken into account for interpreting GISAXS patterns is the sensitivity of GISAXS to facetting and thus its capacity to extract the island shape. The latter is strongly dependent on the island size. For islands with an average volume smaller than ∼20 nm3, the shape cannot be determined unequivocally. Furthermore, for dense island assemblies with some size dispersity, the identification of steep side-wall facets from the GISAXS patterns is not straightforward as observed for truncated tetrahedron-shaped CoPt3islands.
Integrated analysis of whole genome exon array and array‐comparative genomic hybridization in gastric and colorectal cancer cells
Authors: Furuta Kazuyuki , Arao Tokuzo , Sakai Kazuko , Kimura Hideharu , Nagai Tomoyuki , Tamura Daisuke , Aomatsu Keiichi , Kudo Kanae , Kaneda Hiroyasu , Fujita Yoshihiko , Matsumoto Kazuko , Yamada Yasuhide , Yanagihara Kazuyoshi , Sekijima Masaru , Nishio Kazuto
Published: October 2011

Whole genome‐scale integrated analyses of exon array and array‐comparative genomic hybridization are expected to enable the identification of unknown genetic features of cancer cells. Here, we evaluated this approach in 22 gastric and colorectal cancer cell lines, focusing on protein kinase genes and genes belonging to the cadherin–catenin family. Regarding alternative splicing patterns, several cancer cell lines predominantly expressed isoform 1 of protein kinase A catalytic subunit beta (PRKACB). Paired gastric cancer specimens demonstrated that isoform 1 of PRKACB was a novel cancer‐related variant transcript in gastric cancers. In addition, the exon array analysis clearly identified exon 3 or exon 3–4 skipping in catenin beta 1, a short intron insertion with exon 9 skipping in CDH1, and a deletional transcript of CDH13. These abnormal transcripts were shown to have arisen from small genomic deletions. Meanwhile, an integrated analysis of 11 gastric cancer cell lines revealed that four cell lines amplified fibroblast growth factor receptor 2, with truncated forms observed in two of the cell lines. Gene amplification, and not the truncated form, was found to determine the sensitivity to a fibroblast growth factor receptor inhibitor, indicating that our cell line panel might be useful for cell‐based evaluations of specific inhibitors. Using an integrated analysis, we identified several abnormal transcripts and genomic alterations in gastric and colorectal cancer cells. Our approach might enable genetic changes to be identified more efficiently, and the present results warrant further investigation using clinical samples and integrated analyses. (Cancer Sci 2012; 103: 221–227)
Comparison of three algorithms of non‐invasive markers of fibrosis in chronic hepatitis C
Authors: Sebastiani G. , Halfon P. , Castera L. , Mangia A. , Di Marco V. , Pirisi M. , Voiculescu M. , Bourliere M. , Alberti A.
Published: October 2011

Aliment Pharmacol Ther 2012; 35: 92–104

Background  Preliminary data suggest that performance of non‐invasive markers for liver fibrosis in hepatitis C may improve when combined. Three algorithms based on the combination of Fibrotest, Forns’ index and AST‐to‐platelet ratio (APRI) have been proposed: Sequential Algorithm for Fibrosis Evaluation (SAFE biopsy); Fibropaca algorithm; Leroy algorithm.

Aim  To compare three algorithms to diagnose significant fibrosis (≥F2 by METAVIR) and cirrhosis (F4).

Methods  A total of 1013 HCV monoinfected cases undergoing liver biopsy were consecutively enrolled in seven centres. Fibrotest, APRI and Forns’ index were measured at the time of liver biopsy, considered the reference standard.

Results  Overall, performance of combination algorithms was significantly higher than the single non‐invasive methods (P < 0.0001). SAFE biopsy and Fibropaca algorithm saved a significantly higher number of liver biopsies than the single methods (P < 0.0001). For ≥F2, Fibropaca algorithm saved more biopsies than SAFE biopsy (51.7% vs. 43.8%, P = 0.0003), but with lower accuracy (87.6% vs. 90.3%, P = 0.05). Regarding F4, the number of saved liver biopsies did not differ between SAFE biopsy and Fibropaca algorithm (79.1% vs. 76.2%, P = 0.12). However, SAFE biopsy showed a lower accuracy when compared with Fibropaca algorithm (91.2% vs. 94%, P = 0.02). As to Leroy algorithm, although it showed a good performance for ≥F2 (93.5% accuracy), it saved less liver biopsies than SAFE biopsy and Fibropaca algorithm (29.2% vs. 43.8% and 51.7% respectively, P < 0.0001).

Conclusions  SAFE biopsy and the Fibropaca algorithm have excellent performance for liver fibrosis in hepatitis C, allowing a significant reduction in the need for liver biopsies. They can be useful in clinical practice and for large‐scale screening.
Genetic variation in eggshell crystal size and orientation is large and these traits are correlated with shell thickness and are associated with eggshell matrix protein markers
Authors: Dunn I. C. , Rodríguez‐Navarro A. B. , Mcdade K. , Schmutz M. , Preisinger R. , Waddington D. , Wilson P. W. , Bain M. M.
Published: October 2011

The size and orientation of calcium carbonate crystals influence the structure and strength of the eggshells of chickens. In this study, estimates of heritability were found to be high (0.6) for crystal size and moderate (0.3) for crystal orientation. There was a strong positive correlation (0.65) for crystal size and orientation with the thickness of the shell and, in particular, with the thickness of the mammillary layer. Correlations with shell breaking strength were positive but with a high standard error. This was contrary to expectations, as in man‐made materials smaller crystals would be stronger. We believe the results of this study support the hypothesis that the structural organization of shell, and in particular the mammillary layer, is influenced by crystal size and orientation, especially during the initial phase of calcification. Genetic associations for crystal measurements were observed between haplotype blocks or individual markers for a number of eggshell matrix proteins. Ovalbumin and ovotransferrin (LTF) markers for example were associated with crystal size, while ovocleidin‐116 and ovocalyxin‐32 (RARRES1) markers were associated with crystal orientation. The location of these proteins in the eggshell is consistent with different phases of the shell‐formation process. In conclusion, the variability of crystal size, and to a lesser extent orientation, appears to have a large genetic component, and the formation of calcite crystals are intimately related to the ultrastructure of the eggshell. Moreover, this study also provides evidence that proteins in the shell influence the variability of crystal traits and, in turn, the shell’s thickness profile. The crystal measurements and/or the associated genetic markers may therefore prove to be useful in selection programs to improve eggshell quality.
New pharmacological strategies for treatment of Alzheimer's disease: focus on disease modifying drugs
Authors: Salomone Salvatore , Caraci Filippo , Leggio Gian Marco , Fedotova Julia , Drago Filippo
Published: October 2011

Current approved drug treatments for Alzheimer disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine. These drugs provide symptomatic relief but poorly affect the progression of the disease. Drug discovery has been directed, in the last 10 years, to develop ‘disease modifying drugs’ hopefully able to counteract the progression of AD. Because in a chronic, slow progressing pathological process, such as AD, an early start of treatment enhances the chance of success, it is crucial to have biomarkers for early detection of AD‐related brain dysfunction, usable before clinical onset. Reliable early biomarkers need therefore to be prospectively tested for predictive accuracy, with specific cut off values validated in clinical practice. Disease modifying drugs developed so far include drugs to reduce β amyloid (Aβ) production, drugs to prevent Aβ aggregation, drugs to promote Aβ clearance, drugs targeting tau phosphorylation and assembly and other approaches. Unfortunately none of these drugs has demonstrated efficacy in phase 3 studies. The failure of clinical trials with disease modifying drugs raises a number of questions, spanning from methodological flaws to fundamental understanding of AD pathophysiology and biology. Recently, new diagnostic criteria applicable to presymptomatic stages of AD have been published. These new criteria may impact on drug development, such that future trials on disease modifying drugs will include populations susceptible to AD, before clinical onset. Specific problems with completed trials and hopes with ongoing trials are discussed in this review.
M-ficolin levels are associated with the occurrence of severe infections in patients with haematological cancer undergoing chemotherapy
Authors: Ameye L , Paesmans M , Thiel S , Jensenius J C , Aoun M
Published: October 2011

The pattern recognition molecules H-ficolin, L-ficolin and M-ficolin bind to micro-organisms. They activate the lectin pathway of complement through mannan-binding lectin (MBL)-associated serine proteases (MASPs). Association between low MBL levels and infections in patients undergoing chemotherapy for haematological diseases has been observed previously. We now examine for MASP-2, MASP-3 and ficolin levels. We assessed the concentration of lectin pathway molecules as risk factors for infection in patients with haematological malignancy undergoing chemotherapy. Samples taken before the initiation of chemotherapy covering 117 chemotherapy cycles in 105 patients were available. MASPs and ficolins were measured by time-resolved immunoflourometric assays and the levels related to parameters of infections. End-points included febrile neutropenia, documented infections, bacteraemia or severe infections. Lower M-ficolin concentrations were found in patients who developed a severe infection: median 0·27 µg/ml compared to 0·47 µg/ml in patients who did not develop a severe infection (P = 0·01). Conversely, MASP-2 was higher in these patients: median 0·53 µg/ml compared to 0·37 µg/ml, respectively (P = 0·008). When considering M-ficolin levels below 0·36 µg/ml as deficient, the time to development of severe infection was shorter in the M-ficolin deficient group: the hazard ratio was 2·60 (95% confidence interval: 1·23–5·49). No associations were revealed between infections and H-ficolin, L-ficolin or MASP-3. Patients with low M-ficolin are more likely to develop severe infections, whereas MASP-2 showed the opposite.
Identification and long‐term observation of early joint damage by magnetic resonance imaging in clinically asymptomatic joints in patients with haemophilia A or B despite prophylaxis
Authors: OLIVIERI M. , KURNIK K. , PFLUGER T. , BIDLINGMAIER C.
Published: October 2011

Summary.  Severe haemophilia is associated with recurrent joint bleeds, which can lead to haemophilic arthropathy. Subclinical joint bleeds have also been associated with joint damage detected using magnetic resonance imaging (MRI). We investigated the development of early changes in clinically asymptomatic joints using MRI in haemophilia A or B patients receiving prophylactic therapy. In this single‐centre retrospective cohort study, patients with clinical evidence of joint damage in one ankle and one clinically asymptomatic ankle, in which we performed an MRI scan of both ankles in one session, were enrolled. MRI findings were graded using a 4‐point scoring system (0 = normal findings and III = severe joint damage). Since 2000, 38 MRIs in 26 patients have been performed. Starting at a median age of 4 years, 23 patients received prophylaxis 2–3 times weekly. On‐demand treatment was performed in three patients. Eight patients (31%) presented with an MRI score of 0, 12 (46%) had a score of I, four (15%) had a score of II, and two (8%) had a score of III in the clinically unaffected ankle. The six patients with MRI scores of II and III had started regular prophylaxis between the ages of 2 years and 15 years; none had developed an inhibitor or experienced a clinically evident bleed in the asymptomatic ankle. During our study, five of 26 patients had a worsening of MRI findings without experiencing a joint bleed. Early morphological changes in clinically asymptomatic ankles can be detected using MRI, despite adequate prophylaxis.
Transcription of detoxification genes after permethrin selection in the mosquito Aedes aegypti
Authors: Saavedra‐Rodriguez K. , Suarez A. F. , Salas I. F. , Strode C. , Ranson H. , Hemingway J. , Black IV W. C.
Published: October 2011

Changes in gene expression before, during and after five generations of permethrin laboratory selection were monitored in six strains of Aedes aegypti: five F2–F3 collections from the Yucatán Peninsula of Mexico and one F2 from Iquitos, Peru. Three biological replicate lines were generated for each strain. The response to selection was measured as changes in the lethal and knockdown permethrin concentrations (LC50, KC50) and in the frequency of the Ile1,016 substitution in the voltage‐gated sodium channel (para) gene. Changes in expression of 290 metabolic detoxification genes were measured using the ‘Aedes Detox’ microarray. Selection simultaneously increased the LC50, KC50 and Ile1,016 frequency. There was an inverse relationship between Ile1,016 frequency and the numbers of differentially transcribed genes. The Iquitos strain lacked the Ile1,016 allele and 51 genes were differentially transcribed after selection as compared with 10–18 genes in the Mexican strains. Very few of the same genes were differentially transcribed among field strains but 10 cytochrome P450 genes were upregulated in more than one strain. Laboratory adaptation to permethrin in Ae. aegypti is genetically complex and largely conditioned by geographic origin and pre‐existing target site insensitivity in the para gene. The lack of uniformity in the genes that responded to artificial selection as well as differences in the direction of their responses challenges the assumption that one or a few genes control permethrin metabolic resistance. Attempts to identify one or a few metabolic genes that are predictably associated with permethrin adaptation may be futile.
Doppler ultrasound to detect pulpal blood flow changes during local anaesthesia
Authors: Yoon M. J. , Lee S. J. , Kim E. , Park S. H.
Published: October 2011

Yoon MJ, Lee SJ, Kim E, Park SH. Doppler ultrasound to detect pulpal blood flow changes during local anaesthesia. International Endodontic Journal, 45, 83–87, 2012.

Aim  To examine whether Doppler ultrasound can detect changes in pulpal blood flow after infiltration anaesthesia.

Methodology  Changes in pulpal blood flow in maxillary central incisor teeth of 18 patients (mean age 26.7 years, 13 men, five women) after infiltration anaesthesia were examined. Before infiltration anaesthesia, the pulpal blood flow was measured using Doppler ultrasound. A local anaesthetic solution containing 2% lidocaine with 1 : 80 000 epinephrine was injected into the submucosa above the experimental tooth. The Doppler ultrasound test was carried out at 5, 10, 20, 30, 45 and 60 min after infiltration. The parameters were Vas (maximum linear velocity, cm s−1), Vam (average linear velocity, cm s−1) and Vakd (minimum linear velocity, cm s−1), which are indicators of the level of blood flow. The mixed procedure at the 95% confidence interval was used to examine the changes in pulpal blood flow after the injection.

Results  The linear velocity profiles (Vas, Vam, and Vakd) decreased sharply 5 min after anaesthesia and then reduced continuously for 30 min. The maximum degree of blood flow reduction in Vas, Vam and Vakd was 58%, 83% and 82%, respectively. After 30 min, the linear velocities increased gradually. The Vam returned to the pre‐anaesthesia state at 60 minutes but the Vas and Vakd did not recover completely.

Conclusions  Doppler ultrasound can detect changes in pulpal blood flow after infiltration anaesthesia. In the future, Doppler ultrasound can be used as a tool for measuring pulpal blood flow.
The transplant team’s role with regard to establishing contact between an organ recipient and the family of a cadaver organ donor
Authors: Azuri Pazit , Tabak Nili
Published: October 2011

Aims and objectives.  To understand how the recipients of cadaver‐harvested organs and donor families perceive the role of the transplant team and transplant coordinator in bringing them into contact.

Background.  Studies dispute the benefits and disbenefits of contact and their differential weights with the two parties. For the donor family, contact with the recipient after a successful transplant renders positive meaning to the tragedy of the family’s loss, but expectations of the recipient can also be disappointed. For recipients, contact with the donor family lets them express gratitude and shake off the guilt of having their life saved by a death but can also draw them into the family’s mourning and into feeling the family are owed a ‘return’ for their life‐saving gift. The transplant team have to weigh these potential benefits and disbenefits. If the answer is positive, what should they do to bring the contact about?

Design.  A sample of 135 donor family members and organ recipients (representing all successful transplants in Israel from 1998–2007) were interviewed by structured questionnaire. Some had made contact, some not.

Method.  Data were analysed by means, frequencies and correlation coefficients.

Results.  Far more ‘contacters’ than ‘non‐contacters’ wanted the transplant coordinator to take an active role in establishing contact. No less than 60% of non‐contacters wanted contact in the future, and 50% were dissatisfied with the absence of contact.

Conclusions.  This is the first study to investigate the benefits and disbenefits of not making contact. Both donor families and organ recipients would respond positively to the coordinator taking the initiative in establishing mutual contact.

Relevance to clinical practice.  Transplant coordinators are given convincing backing for taking the initiative in promoting contact between donor families and organ recipients. The coordinator’s intervention, information and guidance are needed to make a success of such contact.
Evarcha culicivora chooses blood‐fed Anopheles mosquitoes but other East African jumping spiders do not
Authors: JACKSON R. R. , NELSON X. J.
Published: October 2011

Previous research using computer animation and lures made from dead prey has demonstrated that the East African salticid Evarcha culicivora Wesolowska & Jackson (Araneae: Salticidae) feeds indirectly on vertebrate blood by actively choosing blood‐carrying female mosquitoes as prey, and also that it singles out mosquitoes of the genus Anopheles (Diptera: Culicidae) by preference. Here, we demonstrate that E. culicivora's preference is expressed when the species is tested with living prey and that it is unique to E. culicivora. As an alternative hypothesis, we considered the possibility that the preference for blood‐fed female anopheline mosquitoes might be widespread in East African salticids. When live‐prey choice tests were carried out in 19 additional species, there were no instances in which blood‐carrying mosquitoes were chosen significantly more often than other prey. Combined with the findings of previous work, these results suggest that it is possible that specialized predators play a role in the biological control of disease vectors.
Expression of glia maturation factor in neuropathological lesions of Alzheimer's disease
Authors: Thangavel R. , Stolmeier D. , Yang X. , Anantharam P. , Zaheer A.
Published: October 2011

R. Thangavel, D. Stolmeier, X. Yang, P. Anantharam and A. Zaheer (2012) Neuropathology and Applied Neurobiology38, 572–581

Expression of glia maturation factor in neuropathological lesions of Alzheimer's disease

Aims: The pathology of Alzheimer's disease (AD) is characterized by the presence of amyloid plaques (APs), neurofibrillary tangles (NFTs), degenerating neurones, and an abundance of reactive astrocytes and microglia. We aim to examine the association between glia maturation factor (GMF) expression, activated astrocytes/microglia, APs and NFTs in AD‐affected brain regions. Methods: Brain sections were stained with Thioflavin‐S to study AD pathology and sequentially immunolabeled with antibodies against GMF, glial fibrillary acidic protein (marker for reactive astrocytes), and Ionized calcium binding adaptor molecule 1 (Iba‐1, marker for activated microglia) followed by visualization with avidin‐biotin peroxidase complex. Results: Our double immunofluorescence labelling with cell‐specific markers demonstrated the glial localization of GMF. The immunohistochemical data showed that APs and NFTs are associated with increased expression of GMF in reactive glia of AD brains compared with non‐AD controls. Conclusions: This is the first report that shows GMF, a mediator of central nervous system inflammation, is expressed in the brain regions affected in AD and that GMF is mainly localized in reactive astrocytes surrounding APs/NFTs. The distribution of GMF‐immunoreactive cells in and around Thioflavin‐S stained APs and NFTs suggests involvement of GMF in inflammatory responses through reactive glia and a role of GMF in AD pathology.
A third species of the relict family Epiophlebiidae discovered in China (Odonata: Epiproctophora)
Authors: LI JING‐KE , NEL ANDRÉ , ZHANG XUE‐PING , FLECK GUNTHER , GAO MEI‐XIANG , LIN LIN , ZHOU JIA
Published: October 2011

Epiophlebia sinensis
sp.n., a third species of the relict odonatan family Epiophlebiidae, is described from two male adults collected in Heilongjiang province, China. The new species lives in an environment rather similar to that of the two other species, E. superstes and E. laidlawi, i.e. along cold streams in a coniferous and deciduous forest. Possible explanations for the lack of fossil Epiophlebiidae and the biogeography of these damsel‐dragonflies are proposed.
Automated washing of human progenitor cells: evaluation of apoptosis and cell necrosis
Authors: Scerpa M. C. , Daniele N. , Landi F. , Caniglia M. , Cometa A. M. , Ciammetti C. , Rossi C. , Locatelli F. , Isacchi G. , Zinno F.
Published: October 2011

Background: High‐dose chemotherapy followed by reinfusion of autologous stem cells harvested from peripheral blood has been increasingly applied for a variety of disorders.

The critical importance of cell dose in the clinical outcome, after transplant, has motivated the need to develop techniques aimed at reducing cell losses and increasing reproducibility.

Objectives: The aim of this study is to evaluate the efficacy of the Sepax S‐100 device to process thawed HPC‐A products in comparison with manual procedure.

Methods/Materials: We have analysed viability, total nucleated cells (TNC), haematopoietic progenitors and CD34+ cells recovery.

Results: The TNC and CD34+ cells recovery in the automatic procedure was of 91·9% (73–100; SD ± 12·60) and 86·7% (69–100; SD ± 10·21), respectively. Instead the recovery of TNC and CD34+ cells using the manual method was of 84·7% (47–100; SD ± 22·9) and 80·29% (23–100; SD ± 25·96).

The results, obtained from the assessment of viability of CD34+ both 7‐AAD)+ and AnnV+ showed a high percentage of necrosis and apoptosis in this cell subset by using the manual procedure in respect to the Sepax automated system.

Conclusion: Overall, our data suggest that the automated washing procedure is safe and suitable for processing of thawed HPC‐A products and can be daily used in clinical routine.
Hierarchical analysis of anaemia deferral in blood donor candidates: the individual in the population perspective
Authors: Oliveira C. Di Lorenzo , Martins G. , Custer B. , Proietti F. A. , Carneiro‐Proietti A. B. F. , César C. Comini
Published: October 2011

Background and objectives: Deferral due to anaemia is common in blood donor selection, mainly owing to iron deficiency. This study analysed the prevalence of anaemia, its individual and group‐associated factors in 335 095 blood donor candidates in the Hemominas Foundation, a public blood centre in Minas Gerais State, Brazil.

Materials and methods: For the hierarchical analysis, gender, self‐reported skin colour and age were included as independent variables at the individual level. Second level variables included proportion of self‐reported white, male proportion, prevalence of sickle cell trait and Human Development Index (HDI) for the cities where the blood centres were located.

Results: Deferral due to anaemia was 9·71% in the donor population in the present study. Differences among geographic areas throughout the State were observed; living in an area with lower HDI (P < 0·032), female gender and non‐white skin colour (both P < 0·001) were significantly associated with anaemia. Cities with a lower HDI had higher prevalence rates of anaemia when compared with the others. Anaemia was more pronounced among female and non‐white donors and in the northern part of the State.

Conclusion: A high deferral of blood donors due to anaemia, mostly associated with poverty was observed and deserves attention from the public health perspective. Blood centres should consider the profile of donors and their geographic location when planning mobile blood collection or regional campaigns.
Audio‐video decision support for patients: the documentary genré as a basis for decision aids
Authors: Volandes Angelo E. , Barry Michael J. , Wood Fiona , Elwyn Glyn
Published: October 2011

Objective Decision support tools are increasingly using audio‐visual materials. However, disagreement exists about the use of audio‐visual materials as they may be subjective and biased.

Methods This is a literature review of the major texts for documentary film studies to extrapolate issues of objectivity and bias from film to decision support tools.

Results The key features of documentary films are that they attempt to portray real events and that the attempted reality is always filtered through the lens of the filmmaker. The same key features can be said of decision support tools that use audio‐visual materials. Three concerns arising from documentary film studies as they apply to the use of audio‐visual materials in decision support tools include whose perspective matters (stakeholder bias), how to choose among audio‐visual materials (selection bias) and how to ensure objectivity (editorial bias).

Discussion Decision science needs to start a debate about how audio‐visual materials are to be used in decision support tools. Simply because audio‐visual materials may be subjective and open to bias does not mean that we should not use them.

Conclusion Methods need to be found to ensure consensus around balance and editorial control, such that audio‐visual materials can be used.