bluuebunny/crossref_metadata_2025 huggingface dataset:
Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing‐remitting multiple sclerosis
Authors: Belachew S. , Phan‐Ba R. , Bartholomé E. , Delvaux V. , Hansen I. , Calay P. , Hafsi K. E. , Moonen G. , Tshibanda L. , Vokaer M.
Published: June 2010

Background:  Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing‐remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease‐modifying treatments (DMTs).

Methods:  A retrospective, observational study was carried out. All patients (n = 45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon‐beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium‐enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25‐Foot Walk Test and on the Timed 100‐Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment.

Results:  Sixty‐two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse‐mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients.

Conclusions:  These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs.
A Validation Study of Type 2 Diabetes‐related Variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ Genes in one Endogamous Ethnic Group of North India
Authors: Gupta Vipin , Khadgawat Rajesh , NG Hon Keung Tony , Kumar Satish , Aggarwal Ajay , Rao Vadlamudi Raghavendra , Sachdeva M. P.
Published: June 2010

The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18‐clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan‐based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p‐value = 0.00191; p‐value = 0.00179, respectively), and odds ratios of 2.1 (dominant‐model) and 2.0 (recessive‐model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist‐Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single‐SNP, combined‐SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally‐learned sedentary lifestyle and fat‐enriched dietary habits, WHR rather than body‐mass‐index emerged as a robust predictor of risk for T2D in this population.
Genetic Diversity of the Fragile X Syndrome Gene (FMR1) in a Large Sub‐Saharan West African Population
Authors: Peprah Emmanuel K. , Allen Emily G. , Williams Scott M. , Woodard Laresa M. , Sherman Stephanie L.
Published: June 2010

Fragile X syndrome (OMIM #300624) is caused by the expansion of a CGG trinucleotide repeat found in the 5′ untranslated region of the X‐linked FMR1 gene. Although examinations of characteristics associated with repeat instability and expansion of the CGG repeat upon transmission from parent to offspring has occurred in various world populations, none has been conducted in large Sub‐Saharan African populations. We have examined the FMR1 CGG repeat structure in a sample of 350 males drawn from the general population of Ghana. We found that Ghanaians and African Americans have similar allele frequency distributions of CGG repeat and its flanking STR markers, DXS548 and FRAXAC1. However, the distribution of the more complex marker, FRAXAC2, is significantly different. The haplotype structure of the FMR1 locus indicated that Ghanaians share several haplotypes with African Americans and Caucasians that are associated with the expanded full mutation. In Ghanaians, the majority of repeat structures contained two AGG interruptions, however, the majority of intermediate alleles (35–49) lacked AGG interruptions. Overall, we demonstrate that allelic diversity of the FMR1 locus among Ghanaians is comparable to African Americans, but includes a minority of CGG array structures not found in other populations.
Dynamic morphological changes in the skulls of mice mimicking human Apert syndrome resulting from gain‐of‐function mutation of FGFR2 (P253R)
Authors: Du Xiaolan , Weng Tujun , Sun Qidi , Su Nan , Chen Zhi , Qi Huabing , Jin Ming , Yin Liangjun , He Qifen , Chen Lin
Published: June 2010

Apert syndrome is caused mainly by gain‐of‐function mutations of fibroblast growth factor receptor 2. We have generated a mouse model (Fgfr2+/P253R) mimicking human Apert syndrome resulting from fibroblast growth factor receptor 2 Pro253Arg mutation using the knock‐in approach. This mouse model in general has the characteristic skull morphology similar to that in humans with Apert syndrome. To characterize the detailed changes of form in the overall skull and its major anatomic structures, euclidean distance matrix analysis was used to quantitatively compare the form and growth difference between the skulls of mutants and their wild‐type controls. There were substantial morphological differences between the skulls of mutants and their controls at 4 and 8 weeks of age (P < 0.01). The mutants showed shortened skull dimensions along the rostrocaudal axis, especially in their face. The width of the frontal bone and the distance between the two orbits were broadened mediolaterally. The neurocrania were significantly increased along the dorsoventral axis and slightly increased along the mediolateral axis, and also had anteriorly displayed opisthion along the rostrocaudal axis. Compared with wild‐type, the mutant mandible had an anteriorly displaced coronoid process and mandibular condyle along the rostrocaudal axis. We further found that there was catch‐up growth in the nasal bone, maxilla, zygomatic bone and some regions of the mandible of the mutant skulls during the 4–8‐week interval. The above‐mentioned findings further validate the Fgfr2+/P253R mouse strain as a good model for human Apert syndrome. The changes in form characterized in this study will help to elucidate the mechanisms through which the Pro253Arg mutation in fibroblast growth factor receptor 2 affects craniofacial development and causes Apert syndrome.
The development of the ancient irrigation system at Engaruka, northern Tanzania: physical and societal factors
Authors: WESTERBERG LARS‐OVE , HOLMGREN KARIN , BÖRJESON LOWE , HÅKANSSON N. THOMAS , LAULUMAA VESA , RYNER MARIA , ÖBERG HELENA
Published: June 2010

Climate data from Empakaai Crater in northern Tanzania, covering the last 1200 years, are related to the establishment, development and decline of the ancient irrigation system at Engaruka. New dates for the system are linked to reconstructed climatic variations and historical data on long‐distance and regional trade and migration patterns. A shift from a comparatively humid climate to drier conditions in the 1400s prompted the establishment of irrigated agriculture at Engaruka, and a flourishing long‐distance trade increased its value as a water and food source for passing caravans. Once established, the land‐use system at Engaruka was sufficiently resilient to survive and even intensify during much drier climate from c. 1500 to 1670 CE (Common Era) and during the decline of caravan trade between c. 1550 and 1750. The ancient land‐use system probably reached its maximum extension during the humid conditions between 1670 and 1740, and was deserted in the early to mid 1800s, presumably as a result of the added effects of climate deterioration, the Maasai expansion, and change of livelihood strategies as agriculturalists became pastoralists. Towards the end of the 1800s irrigated agriculture was again established at Engaruka, in part driven by the transfer from pastoral to agricultural livelihoods caused by the Rinderpest.
LONG‐RUN INEQUALITY AND SHORT‐RUN INSTABILITY OF MEN'S AND WOMEN'S EARNINGS IN CANADA
Authors: Beach Charles M. , Finnie Ross , Gray David
Published: June 2010

This paper examines the variability of workers’ earnings in Canada over the period 1982–2006. We decompose the total variance of workers’ earnings into a ‘permanent’ component between workers and a ‘transitory’ earnings instability component over time for given workers. We then investigate the statistical relationships between these components and indicators for the business cycle. The most marked change in earnings variances in Canada since 1982 is the general rise in total earnings variance, which is essentially driven by a quite dramatic rise in long‐run earnings inequality. The patterns across age categories of the two variance components are almost opposite. Long‐run earnings inequality generally rises with age, but earnings instability is seen to generally decline with age, so that earnings instability is markedly highest among entry age workers. Unemployment rate effects are positive on almost all variance measures, while higher unemployment is associated with widened long‐run earnings differentials and greater short‐run earnings instability.
Monoclonal antibody TGN1412 trial failure explained by species differences in CD28 expression on CD4+ effector memory T‐cells
Authors: Eastwood D , Findlay L , Poole S , Bird C , Wadhwa M , Moore M , Burns C , Thorpe R , Stebbings R
Published: June 2010

BACKGROUND AND PURPOSE In 2006, a life‐threatening ‘cytokine storm’, not predicted by pre‐clinical safety testing, rapidly occurred in all six healthy volunteers during the phase I clinical trial of the CD28 superagonist monoclonal antibody (mAb) TGN1412. To date, no unequivocal explanation for the failure of TGN1412 to stimulate profound cytokine release in vitro or in vivo in species used for pre‐clinical safety testing has been established. Here, we have identified a species difference almost certainly responsible for this disparate immunopharmacology.

EXPERIMENTAL APPROACH Polychromatic flow cytometry and intracellular cytokine staining were employed to dissect the in vitro immunopharmacology of TGN1412 and other therapeutic mAbs at the cellular level to identify differences between humans and species used for pre‐clinical safety testing.

KEY RESULTS In vitro IL‐2 and IFN‐γ release from CD4+ effector memory T‐cells were key indicators of a TGN1412‐type response. This mechanism of cytokine release differed from that of other therapeutic mAbs, which can cause adverse reactions, because these other mAbs stimulate cytokine release primarily from natural killer cells. In contrast to humans, CD28 is not expressed on the CD4+ effector memory T‐cells of all species used for pre‐clinical safety testing, so cannot be stimulated by TGN1412.

CONCLUSIONS AND IMPLICATIONS It is likely that activation of CD4+ effector memory T‐cells by TGN1412 was responsible for the cytokine storm. Lack of CD28 expression on the CD4+ effector memory T‐cells of species used for pre‐clinical safety testing of TGN1412 offers an explanation for the failure to predict a ‘cytokine storm’ in humans.
A Novel Subcutaneous Counterpulsation Device: Acute Hemodynamic Efficacy During Pharmacologically Induced Hypertension, Hypotension, and Heart Failure
Authors: Bartoli Carlo R. , Wilson Gregory C. , Giridharan Guruprasad A. , Slaughter Mark S. , Sherwood Leslie C. , Spence Paul A. , Prabhu Sumanth D. , Koenig Steven C.
Published: June 2010

The miniaturization of mechanical assist devices and less invasive implantation techniques may lead to earlier intervention in patients with heart failure. As such, we evaluated the effectiveness of a novel, minimally invasive, implantable counterpulsation device (CPD) in augmenting cardiac function during impaired hemodynamics. We compared the efficacy of a 32‐mL stroke volume CPD with a standard 40‐mL intra‐aortic balloon pump (IABP) over a range of clinically relevant pathophysiological conditions. Male calves were instrumented via thoracotomy, the CPD was anastomosed to the left carotid artery, and the IABP was positioned in the descending aorta. Hemodynamic conditions of hypertension, hypotension, and heart failure were pharmacologically simulated and data were recorded during CPD and IABP support (off, 1:2, 1:1 modes) for each condition. In all three pathophysiological conditions, the CPD and IABP produced similar and statistically significant (P < 0.05) increases in coronary artery blood flow normalized to the left ventricular (LV) workload. During hypotension and heart failure conditions, however, the CPD produced significantly greater reductions in LV workload and myocardial oxygen consumption as compared with the IABP. A novel 32‐mL CPD connected to a peripheral artery produced equivalent or greater hemodynamic benefits than a standard 40‐mL IABP during pharmacologically induced hypertension, hypotension, and heart failure conditions.
Genetic research in the blood bank: acceptability to Northern California donors
Authors: Rice Megan S. , Custer Brian S. , Hindes Daniel A. , Hirschler Nora V. , Nguyen Kim‐Anh , Busch Michael P. , Murphy Edward L.
Published: June 2010

BACKGROUND: Blood banks have large altruistic donor populations and existing infrastructure that make them attractive sites for genetic epidemiologic research, but donors' willingness to participate and the impact on blood donation are unknown.

STUDY DESIGN AND METHODS: A total of 2162 blood donors in Northern California responded to a cross‐sectional questionnaire in August and September 2007. Participants were asked their likelihood of participation and future blood donation under three different scenarios: identity‐linked genetic research, identity‐unlinked genetic research, and genetic testing as a service.

RESULTS: The majority of blood donors indicated that they would be likely or very likely to participate in identity‐linked genetic research (67%) and in identity‐unlinked genetic research (54%). While older donors and more frequent donors were more likely to participate in identity‐linked research, younger, Caucasian, more educated, and more frequent donors were more likely to participate in identity‐unlinked research. Less than 10% of donors indicated they would be less likely to donate blood in the future if genetic research was conducted at blood banks. More than 75% of donors would be interested in genetic testing as an optional service at the blood bank, but more than 20% of donors would be less likely to donate if such a service was offered.

CONCLUSION: Overall, we found that the majority of blood donors would be likely to participate in genetic research and that less than 10% would be less inclined to donate if such research was conducted by blood banks.
Understanding the Positive Effects of Graphical Risk Information on Comprehension: Measuring Attention Directed to Written, Tabular, and Graphical Risk Information
Authors: Smerecnik Chris M. R. , Mesters Ilse , Kessels Loes T. E. , Ruiter Robert A. C. , De Vries Nanne K. , De Vries Hein
Published: June 2010

Risk communications are an integral aspect of health education and promotion. However, the commonly used textual risk information is relatively difficult to understand for the average recipient. Consequently, researchers and health promoters have started to focus on so‐called decision aids, such as tables and graphs. Although tabular and graphical risk information more effectively communicate risks than textual risk information, the cognitive mechanisms responsible for this enhancement are unclear. This study aimed to examine two possible mechanisms (i.e., cognitive workload and attention). Cognitive workload (mean pupil size and peak pupil dilation) and attention directed to the risk information (viewing time, number of eye fixations, and eye fixation durations) were both measured in a between‐subjects experimental design. The results suggest that graphical risk information facilitates comprehension of that information because it attracts and holds attention for a longer period of time than textual risk information. Graphs are thus a valuable asset to risk communication practice for two reasons: first, they tend to attract attention and, second, when attended to, they elicit information extraction with relatively little cognitive effort, and finally result in better comprehension.
Sonication of Explanted Cardiac Rhythm Management Devices for the Diagnosis of Pocket Infections and Asymptomatic Bacterial Colonization
Authors: MASON PAMELA K. , DIMARCO JOHN P. , FERGUSON JOHN D. , MAHAPATRA SRIJOY , MANGRUM J. MICHAEL , BILCHICK KENNETH C. , MOORMAN J. RANDALL , LAKE DOUGLAS E. , BERGIN JAMES D.
Published: June 2010

Background: Correct diagnosis of the causative organism is critical for the treatment of pacemaker and defibrillator pocket infections. No gold standard for this exists, although swab and tissue cultures are frequently used. The purpose of this study was to determine the value of ultrasonication of explanted generators in the diagnosis of pocket infections and asymptomatic bacterial colonization.

Methods: Samples were prospectively collected during pacemaker and defibrillator generator extractions for elective replacements, upgrades, or pocket infections. The devices were placed in an ultrasonicator for 5 minutes and the fluid sent for culture, along with swab and tissue cultures.

Results: Eighty‐two patients with pacemakers (n = 46) or defibrillators (n = 36) underwent generator explantation, 66 of these for elective reasons and 16 for pocket infection. In patients with pocket infection, 15 (94%) received a definitive bacterial diagnosis using a combination of all three‐culture modalities. Cultures were positive in 15 sonicated fluid, 13 tissue, and 11 swab samples, with Staphylococcus aureus and other skin flora commonly seen. In asymptomatic patients, 14 (21%) had positive cultures. Cultures were positive in 11 sonicated fluid, eight tissue, and two swab samples. Skin flora was commonly seen, but three of the sonicated fluid cultures grew gram‐negative rods. No patients with asymptomatic colonization developed clinical infection during the follow‐up period.

Conclusions: Ultrasonication is an inexpensive and simple technique that improves the bacteriologic diagnosis of device pocket infections. It also identifies a significant proportion of patients with asymptomatic colonization, although this is not a marker of future pocket infection. (PACE 2011; 34:143–149)
Programming Antitachycardia Pacing for Primary Prevention in Patients With Implantable Cardioverter Defibrillators: Results From the PROVE Trial
Authors: SAEED MOHAMMAD , NEASON CURTIS G. , RAZAVI MEHDI , CHANDIRAMANI SHANKER , ALONSO JOSEPH , NATARAJAN SENTHIL , IP JOHN H. , PERESS DARREN F. , RAMADAS SUMATI , MASSUMI ALI
Published: June 2010

Programming ATP for ICD Patients. Objectives: The PROVE trial was designed to determine if antitachycardia pacing (ATP) is clinically beneficial for primary prevention in patients who have implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT‐Ds).

Background: Use of ICDs and CRT‐Ds reduces mortality in patients with ventricular dysfunction and mild to moderate heart failure. However, in studies of the primary prevention population, shock‐only ICDs are predominantly used, without ATP programming for less painful termination of ventricular tachycardia (VT).

Methods: We conducted a prospective, nonrandomized, multicenter study using market‐released ICDs and CRT‐Ds. Patients received devices programmed to deliver ATP for VT cycle lengths of 270–330 ms. Follow‐up evaluation was performed at 3, 6, and 12 months. The incidence of VT and the rate of successful termination by ATP were analyzed.

Results: Of 830 patients in the study population (men, 73%; mean age, 67.3 ± 12 years), 32% received single‐chamber ICDs, 44% dual‐chamber ICDs, and 24% CRT‐Ds. ATP was attempted for 112 VT episodes in 71 patients, and 103 (92%) of the VT episodes were successfully terminated. Three VT episodes were accelerated by ATP and required termination by ICD shock; 6 episodes terminated spontaneously or by ICD shock.

Conclusions: VT is common in patients without a history of this arrhythmia who have received ICDs or CRT‐Ds for primary prevention indications. Programming ICDs for ATP therapy at the time of implantation could potentially terminate most VT episodes and reduce the number of painful shocks for these patients. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1349‐1354, December 2010)
Initial Experience With a Multielectrode Catheter Equipped With the Single‐Axis Sensor Technology for High‐Density Electroanatomical Mapping in a Swine Model
Authors: BEINART ROY , PERNA FRANCESCO , DANIK STEPHAN , BARRETT CONOR D. , HEIST E. KEVIN , RUSKIN JEREMY , MANSOUR MOUSSA
Published: June 2010

Utility of Single‐Axis Sensor Technology in High‐Density Electroanatomical Mapping. Introduction: Magnetic‐based electroanatomical mapping systems are widely used during catheter ablation. Currently, the size of the sensor incorporated in the catheter to allow its localization is large, prohibiting the placement of more than one sensor on any single catheter. As a result, multielectrode catheters cannot be tracked by the magnetic‐based mapping systems. Single‐axis sensors (SAS) are new generation sensors that are significantly smaller in size. The small size of these new sensors allows the placement of more than one sensor on each catheter, allowing the tracking of multielectrode catheters. The objective of this study is to test the feasibility of creating high‐density magnetic electroanatomical maps using a new generation multielectrode catheter equipped with the SAS technology.

Methods and Results: Anatomical reconstruction of cardiac chambers and the aorta, together with activation mapping of the right atrium during both sinus rhythm and pacing‐induced premature atrial contractions (PACs), were performed in 5 swine using both a conventional mapping catheter and the novel multielectrode catheter equipped with SAS. The multielectrode mapping provided a detailed definition of cardiac anatomy while requiring shorter acquisition times. In addition, mapping of PACs origin was significantly faster using the multielectrode catheter.

Conclusion: The novel multielectrode catheter equipped with the SAS technology can be used in combination with magnetic electroanatomical mapping systems to generate high‐density anatomical reconstructions and activation maps. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1403‐1407, December 2010)
Osteochondritis dissecans (OCD), an endoplasmic reticulum storage disease?: a morphological and molecular study of OCD fragments
Authors: Skagen P. S. , Horn T. , Kruse H. A. , Stærgaard B. , Rapport M. M. , Nicolaisen T.
Published: June 2010

Osteochondritis dissecans (OCD) fragments, cartilage and blood from four patients were used for morphological and molecular analysis. Controls included articular cartilage and blood samples from healthy individuals. Light microscopy and transmission electron microscopy (TEM) showed abnormalities in chondrocytes and extracellular matrix of cartilage from OCD patients. Abnormal type II collagen heterofibrils in “bundles” and chondrocytes with abnormal accumulation of matrix proteins in distended rough endoplasmic reticulum were typical findings. Further, Von Kossa staining and TEM showed empty lacunae close to mineralized “islands” in the cartilage and hypertrophic chondrocytes containing accumulated matrix proteins. Immunostaining revealed: (1) that types I, II, VI and X collagens and aggrecans were deposited intracellulary and (2) co‐localization within the islands of types I, II, X collagens and aggrecan indicating that hypertrophic chondrocytes express a phenotype of bone cells during endochondral ossification. Types I, VI and X collagens were also present across the entire dissecates suggesting that chondrocytes were dedifferentiated. DNA sequencings were non‐conclusive, only single nucleotide polymorphism was found within the COL2A1 gene for one patient. We suggest that OCD lesions are caused by an alteration in chondrocyte matrix synthesis causing an endoplasmic reticulum storage disease phenotype, which disturbs or abrupts endochondral ossification.
Electrophysiological Effects of the Anti‐Cancer Drug Lapatinib on Cardiac Repolarization
Authors: Lee Hyang‐Ae , Kim Eun‐Joo , Hyun Sung‐Ae , Park Sung‐Gurl , Kim Ki‐Suk
Published: June 2010

Abstract:  Lapatinib is one of several tyrosine kinase inhibitors used against solid tumour cancers such as breast and lung cancer. Although lapatinib is associated with a risk of QT prolongation, the effects of the drug on cellular cardiac electrical properties and on action potential duration (APD) have not been studied. To evaluate the potential effects of lapatinib on cardiac repolarization, we investigated its electrophysiological effects using a whole‐cell patch–clamp technique in transiently transfected HEK293 cells expressing human ether‐à‐go‐go (hERG; to examine the rapidly activating delayed rectifier K+ current, IKr), KCNQ1/KCNE1 (to examine the slowly activating delayed rectifier K+ current, IKs), KCNJ2 (to examine the inwardly rectifying K+ current, IK1), or SCN5A (to examine the inward Na+ current, INa) and in rat cardiac myocytes (to examine the inward Ca2+ current, ICa). We also examined its effects on the APD at 90% (APD90) in isolated rabbit Purkinje fibres. In ion channel studies, lapatinib inhibited the hERG current in a concentration‐dependent manner, with a half‐maximum inhibition concentration (IC50) of 0.8 ± 0.09 μm. In contrast, at concentrations up to 3 μm, lapatinib did not significantly reduce the INa, IK1 or ICa amplitudes; at 3 μm, it did slightly inhibit the IKs amplitude (by 19.4 ± 4.7%; p < 0.05). At 5 μm, lapatinib induced prolongation of APD90 by 16.1% (p < 0.05). These results suggest that the APD90‐prolonging effect of lapatinib on rabbit Purkinje fibres is primarily a result of inhibition of the hERG current and IKs, but not INa, IK1 or ICa.
Rectourethral fistula after radical prostatectomy: Transperineal repair in jack‐knife position
Authors: Ho Brian , Ho Kwan‐Lun , Tsu James Hok‐Leung , Ng Raymond Wai‐Man , Law Wai‐Lun , Tam Po‐Chor
Published: June 2010

Background:  Rectourethral fistula is a rare complication of radical prostatectomy. Risk factors include history of pelvic irradiation, cryotherapy, intraoperative rectal injury or transurethral resection of the prostate. Diagnosis of rectourethral fistula requires a high index of suspicion, and complete work‐up with endoscopy and imaging studies. The majority of patients require operative intervention, with approaches ranging from transabdominal, transrectal, transanal, and transperineal routes.

Method:  We report two patients with rectourethral fistula after radical prostatectomy. The first patient was a 59‐year‐old man who underwent an uncomplicated laparoscopic radical prostatectomy for early prostate cancer in another hospital. The second patient was a 64‐year‐old man who had local recurrence after cryotherapy for prostate cancer. He underwent salvage radical prostatectomy in a private hospital, which was complicated by intraoperative rectal injury.

Results:  In both patients, the rectourethral fistulae were successfully repaired with a transperineal approach in the prone jack‐knife position.

Conclusion:  We found that the transperineal approach in the prone jack‐knife position offered excellent exposure, allowed versatile surgical manoeuvres and produced successful repair with good continence outcomes.
Retrospective review of the outcome of post‐chemotherapy retroperitoneal lymph node dissection in the management of metastatic testicular cancer: Local experience
Authors: Chung Vera Y. , Yee Chi‐Hang , Hou See‐Ming , Yip Sidney K.H. , Ng Chi‐Fai
Published: June 2010

Objective:  Post‐chemotherapy retroperitoneal lymph node dissection (RPLND) for metastatic testicular cancer is an uncommon surgical procedure in Hong Kong. Therefore, in the present article, we review the perioperative and long‐term morbidity, as well as the survival outcome for RPLND carried out in a urological centre.

Method:  This is a retrospective study of patients suffering from metastatic testicular cancer with post‐chemotherapy residual mass subjected to RPLND between 1998 and 2008. Patient and tumour parameters including initial presentation, chemotherapy regimens received prior to RPLND, perioperative outcomes, pathology and long‐term results were retrieved from hospital notes and reviewed.

Results:  Seven patients who underwent post‐chemotherapy RPLND were included in the present review. The mean follow‐up time was 63.7 months (range 6–136 months), and no recurrence or mortality was reported in this series. Early perioperative morbidity included pulmonary oedema (one), chylous ascites (one) and wound dehiscence (one). Other than ejaculatory dysfunction in all of the patients, there was no major‐long term complication reported in our series.

Conclusion:  This local series confirmed the survival benefit and association of minimal long‐term morbidity with post‐chemotherapy RPLND.
How do Plant Morphological Characteristics, Species Composition and Richness Regulate Eco‐hydrological Function?
Authors: Wang Zhen‐Hong , Duan Chang‐Qun
Published: June 2010

Although considerable research has focused on the relationship between ecosystem structure and function, interactions of plant morphological characteristics, species composition and richness with eco‐hydrological functions remain unclear. We measured water adherence (i.e. the capacity of a plant species to retain water), documented plant surface morphology and observed surface runoff at three sites in China. The adhering water ratios for each plant species differed, ranging from 17.1% to 151.5% in leaves, and from 14.4% to 41.1% in branches. Small, light‐weight, soft, non‐cuticularized leaves that were densely situated on small branches showed good water adherence. The next best adherence was found by branches with intermediately coarse surfaces. The plant species with high standing biomass also showed good water adherence, and the contribution of a species to total adherence was dependent upon its aboveground standing biomass. Vegetation parameters strongly affected water adherence, whereas the effect of species richness was not significant. Conversely, species richness showed a significant influence on surface runoff. The effect of plant morphological characteristics and composition constitutes a basic process in the regulation of eco‐hydrological function, and vegetation parameters play somewhat different roles in that regulation. The key roles must therefore be considered from a management perspective.
Combinatorial techniques for enhancing neuroprotection
Authors: Kuffler Damien P.
Published: June 2010

Brain and spinal cord (CNS) trauma typically kill a number of neurons, but even more neurons are killed by secondary causes triggered by the initial trauma. Thus, a minor insult may rapidly cause the death of a vastly larger number of neurons and complete paralysis. The best mechanism for reducing the extent of neurological deficits is to minimize the number of neurons killed by post‐trauma sequelae. Neuroprotection techniques take many diverse forms with a breadth too great for a short review. Therefore, this review focuses on the neuroprotection provided by hypothermia and a number of other neuroprotective techniques, when administered singly or in combination, because it is generally found that combinations of applications lead to significantly better neuroprotection than is achieved by any one alone. The combinatorial approach to neuroprotection holds great promise for enhancing the degree of neuroprotection following trauma, leading to maximum maintenance of neurological function.
Processing of whole blood into cellular components and plasma
Authors: Devine D. V. , Howe D.
Published: June 2010

Continuous improvement in the area of blood component production has brought an increased emphasis on process control hand in hand with the creation of processes that provide a greater degree of standardization of the products. This work has included the systematic characterization of products produced using routine high throughput systems to understand which elements of the production process give rise either to non‐conforming products or to high levels of variation in products. Such information leads to an opportunity to rethink our general approach to the assessment of component quality. Much of the recent progress in blood component production, including new developments in automation, has raised expectations of parallel opportunities to improve product quality through improved technology. The areas where we still lack a good understanding of the factors contributing to overall component quality are excellent targets for future research effort.
Current and future aspects of HLA in transfusion medicine, transplantation and cellular therapy
Authors: Mayr W. R.
Published: June 2010

The current and future role of gene products of the HLA system in transfusion medicine, transplantation and cellular therapy is briefly discussed.
Current status of pathogen inactivation methods
Authors: AuBuchon J. P.
Published: June 2010

Although improved donor selection criteria and tests of increasing sensitivity have dramatically reduced the risks of transfusion‐transmitted infectious disease, multiple potential means exist for a pathogen to escape detection and injure a recipient: a window period remains in which an infectious donor cannot be detected; some transmissions (e.g. bacterial contamination of platelets) have detection methods that are far from the desired capabilities; and ‘emerging’ pathogens continue to represent a risk to recipients until effective testing strategies are developed and implemented. Pathogen inactivation of labile blood components represents a means of addressing all three of these shortcomings simultaneously as they have for plasma derivatives. Multiple effective means of pathogen inactivation have been validated and put into use for plasma and for platelet components. While not yet universally implemented, these appear to have an acceptable toxicity profile and retain a clinically useful – although slightly diminished – degree of efficacy that is not associated with increased usage. Some of these techniques, such as solvent–detergent treatment of plasma, appear to offer benefits beyond avoidance of infectious disease; in this case, the pooling involved in the process, while creating a risk for dissemination of non‐enveloped viruses, appears to reduce the risk of TRALI considerably. Promising systems for pathogen inactivation of red blood cells and whole blood are under development and would complete the spectrum of treatment across all labile components. While some jurisdictions, most notably the United States, interpret the completed clinical trials as not yet presenting adequate benefit to balance perceived risks, the primary impediments to implementation would appear to fall more into the logistic than scientific category. Is there sufficient benefit to warrant implementation of pathogen inactivation for plasma and platelets before red cell treatment is feasible? How can the processes be accomplished while minimizing cost to the system? How will each country’s healthcare system accommodate the inevitably increased expense for this additional production step? What impact will a fully pathogen‐inactivated blood supply have on clinicians’ conception of transfusion risk and thus blood utilization? This review provides an overview of data available from clinical trials and attempts to identify a path towards improving transfusion recipient safety.
Donor hemovigilance: safety as the first priority of blood donor management
Authors: Benjamin R. J.
Published: June 2010

Background  The American Red Cross instituted a donor hemovigilance program (HVP) in its 35 regional blood centres in 2003 to document adverse events occurring at the time of donation or reported later. The aims are to describe and quantitate rare events using standard definitions, define risk factors, design specific interventions and to assess outcomes. In the 1990s, most US blood centres converted to 500 ml whole blood (WB) collection bags to maximize blood collection. The AABB (formerly known as the American Association of Blood Banks) instituted a standard (#5.4.1.A) to permit a maximum blood loss of 10·5 ml/kg and minimum donor weight of 50 kg (110 lb), allowing 525 ml of blood to be removed from the smallest donors. In the last decade, the majority of States have enacted legislation to allow 16‐year‐old donors to donate with parental consent.

Methods  Standardized adverse event definitions and reporting were instituted in 2003, and adverse event data were collated and analysed at the National Medical Office. Standard database and statistical analytical methods were utilized. Estimated blood volume was calculated based on height, weight and gender, using the method of Nadler et al. Surgery 1962; 51:224–231.

Results  Analysis of HVP data from 2002 to 2006 highlighted that young, first time, female donors were at risk for vasovagal reactions, injuries related to falls and the need for outside medical care. Multivariate analysis revealed young age, low estimated blood volume (<3·5 l) (EBV) and first‐time donation status as major independent risk factors. Calculation of EBV revealed that current AABB standards allow, and CFR limits do not prevent, 15–20% blood loss of EBV from short, low‐weight female donors.

Interventions to reduce vasovagal reactions were piloted, starting in 2008, including: (i) a controlled environment through standardized work guidance, physical setup and staffing matrices; (ii) improved donor and parent educational material prior to donation; (iii) enhanced donor monitoring post donation; (iv) fluid intake encouraged within 30 minutes of donation; (v) distraction and muscle tension techniques; (vi) use of apheresis double red cell collection in eligible donors; (vii) enhanced post donation instructions to donors and patients; (viii) implementation of selective height and weight restrictions in donors <19 years old to avoid collection from donors with EBV <3·5 l.

Conclusions  A national HVP has highlighted the issue of vasovagal syncope‐like reactions in young first‐time donors with low EBV leading to multiple interventions designed to reduce risk. Outcomes are being assessed and monitored. Current AABB standards do not adequately protect young donors with low height/weight from excess blood loss in the United States.
Three respiratory gases and the red cell: oxygen, carbon dioxide and nitric oxide
Authors: (Sunny)Dzik W.
Published: June 2010

Three vital gases – oxygen, carbon dioxide and nitrogen – intersect at the level of the human red blood cell. The delivery of oxygen to all tissues by red cells is essential to human life. Evolution has created a complex molecule, haemoglobin, designed for efficient uptake and off‐loading of oxygen. Iron rests at the centre of the haeme moiety and is critical for oxygen exchange. Although studied for over a century, some details of oxygen transport by the red cell remain uncertain. Recent research has focused on the interaction of haemoglobin with a complex of cell‐membrane proteins centred on band 3. In addition, there is renewed interest in the question of whether or not stored red cells deliver oxygen to tissues as well as fresh red cells. The interactions of CO2 with the red cell have drawn far less research attention. Plasma CO2 released by tissues serves as an essential trigger for oxygen release by haemoglobin via the Bohr effect. CO2 transport depends on conversion of CO2 to bicarbonate via red cell carbonic anhydrase in conjunction with chloride exchange across the red cell membrane. There is very little research on the effect of blood storage on CO2 excretion although this aspect of respiratory physiology is every bit as important as oxygen delivery. Nitric oxide (NO) physiology is directly related to oxygen delivery by the red cell. NO serves a local vasodilator to increase blood flow to hypoxic tissue beds. NO binds strongly to haemoglobin which serves as an NO sink. Under normal conditions, plasma NO synthesized by endothelial cells is not consumed by red cell haemoglobin because of a diffusion blockade across the red cell membrane that results from membrane structures not fully identified. Under conditions of red cell lysis, free haemoglobin scavenges NO reducing local vasodilation. Scavenging of NO is now recognized as an important component of the physiologic response to chronic haemolysis and is very likely to play an important role in the renal lesion of acute haemolysis. The three RBC gases are also the three principal gases of the Earth’s atmosphere. While CO2 is the least abundant of the three by far, it is also likely to be the most critical to the future survival of life on Earth – because small further increases in the concentration of CO2 will result in continued climate change, and large increases will be deadly. Thus, the management of three vital gases by the collection of red cells found within us has broad similarities to the collective management of our atmosphere. Just as the survival of individual tissue cells depends upon proper balance of these three respiratory gases, so too will their proper balance be the key to survival of life on Earth.
Demographic changes: the impact for safe blood supply
Authors: Greinacher A. , Fendrich K. , Hoffmann W.
Published: June 2010

The population structure in most European countries is currently changing with a shift from younger to older age groups. Only sparse data exist on the impact of these demographic changes on future blood demand and supply. Data on blood recipients are sparse and unconnected to data on blood donors. Based on studies in North America and Europe on the impact of demographic changes on future blood supply, the demographic trends will affect many regions in the Western world similarly. These effects are most pronounced in the new member states of the European Union where birth rates declined abruptly after 1989. Co‐ordinated efforts will be required to prevent blood shortages based upon these demographic trends in Western societies. The second part of this review provides examples of different methodological approaches to obtain data on the sociodemographic background of the blood donor population.
Bleeding complications: therapeutic strategies in haemostasis
Authors: Spannagl M.
Published: June 2010

Several haemostyptic agents as well as cellular and plasmatic blood products are available for treatment of bleeding complications. Selective application of these compounds according to the patient’s haemostatic disturbances is superior to standard application of cellular concentrates and fresh frozen plasma. Near‐patient testing of whole blood coagulation and fibrinolysis has been suggested for goal directed therapy. Recent data show reduction of consumption of blood products using algorithms and tailored therapy.
Established ways to keep donor’s interest alive
Authors: Ringwald J.
Published: June 2010

Background  The future demographic changes will be associated with an enhancement of the worldwide shortage of blood. The ageing of the population in developed countries is associated with a decrease in young individuals being potentially eligible to donate blood and an increase in older individuals who might be in the need of blood transfusion. Therefore, the retention of active blood donors (BD) is becoming more important. A substantial increase in blood donations could be achieved by a relatively small increase in BD return. It is the task of blood donation services (BDSs) to elaborate specific and adequate measures to increase the BD’s likelihood to return. Successful BD retention programmes are viable to ensure a sufficient supply with blood and blood components at present and the upcoming years.

Aims  To give recommendations for BD retention strategies based on a survey of potential and established measures how BD’s interest could be kept alive.

Methods  With focus on the last decade, literature about internal and external influences on BD’s intention to regular blood donation and their actual return behaviour was reviewed. Furthermore, a special aspect was drawn on published articles about established or potential measures to increase BD’s return‐rate. Based on this information, different ways how BD’s interest could be kept alive were suggested.

Results  Overall, individuals of younger age (< 30–40 years), women, those with a lower education level are less likely to return to blood donation. External influences of friends, family or co‐workers are import for starting a BD career. To become a committed BD, however, a high level of intrinsic motivation is needed. To keep BD’s interest alive for a long time, BDSs should focus on the following to increase the satisfaction of the BD: Make blood donation a good experience and as convenient as possible, reduce adverse events and anxiety, and train and motivate your staff. This could be further supported by an intensive and active communication with the BDs right from the start, the application of loyalty builders to establish BD identity, and the appropriate use of incentives. Finally, temporarily deferred BDs should ask to return personally and advertisement programmes for repeat BDs should appeal on personal motivation and moral norms. However, BDS should always try to adapt their measures on their target population considering that people are different all around the world. Moreover, some promotion programmes should be even tailored for distinct subgroups of BDs to have a successful outcome.

Conclusions  There is quite a number of ways to keep BDs interest alive and to start a career as a regular and committed BD. In this context, the self‐identification as a BD is definitely of major importance. BDSs are challenged to support this developmental process. They have to make sure that blood donation is associated with a good experience for the BD, making him or her feeling good and happy.
Prenatal rhesus testing
Authors: Legler T. J.
Published: June 2010

Background  Prenatal rhesus testing is currently not well standardized. The clinical guidelines and technologies differ between countries and regions.

Aims  To facilitate implementation of non‐invasive prenatal diagnosis of the foetal Rh type (NIPD of Rh) from cell free foetal DNA in maternal plasma. To propel the implementation of targeted administration of anti‐D immunoglobulin only to those women who carry a D‐positive foetus.

Materials and Methods  A review of the English literature was performed.

Results  For foetal DNA extraction a variety of detailed protocols have been published which allow the prediction of the foetal Rh phenotype with an accuracy of above 99%. There are manual as well as automated systems on the market. Several thousand D‐negative women have been tested in clinical trials for the foetal D status with real‐time PCR. Primers and probes have been designed to be applicable in multi‐ethnic populations despite the complex genetic background of the Rh blood group system. A control for foetal DNA has been published in some papers in order to provide an in‐process control for cases where the foetus is D (C, c or E) negative.

Discussion  The scientific community reached a high level of accuracy which allows NIPD of Rh on a large scale.

Conclusion  NIPD of Rh is now available for all alloimmunized women. In most countries health politicians need to change guidelines now before targeted administration of anti‐D immunoglobulin can be offered by obstetricians.