bluuebunny/crossref_metadata_2025 huggingface dataset:
Breed Variations in the Incidence of Pyometra and Mammary Tumours in Swedish Dogs
Authors: Jitpean S , Hagman R , Ström Holst B , Höglund OV , Pettersson A , Egenvall A
Published: December 2012

Contents

Dogs enrolled in a Swedish insurance company (during 1995–2006) were studied for development of pyometra and mammary tumours (MTs), with special attention to breed and age. There were over 260 000 female dogs with over 1 000 000 dog‐years at risk (DYAR) in the database, using data on bitches up to 10 years of age and 110 breeds with over 1000 DYAR. In total, 20 423 bitches were diagnosed with pyometra and 11 758 with MTs and 30 131 with either or both of the two diseases. The incidence rate (IR) for pyometra was 199 (95% CI 196–202), for MTs 112 (95% CI 110–114) and for either or both of the two diseases 297 (95% CI 294–301) dogs per 10 000 DYAR. The mean age of diagnosis pyometra was 7.0 years (SD ± 2.2), MTs 8.0 years (SD ± 1.6). In all breeds, the overall proportion of the bitches that developed disease by 10 years of age was for pyometra 19%, MTs 13%, and either or both of two diseases 30%. The top 10 breeds diagnosed with either or both of the two diseases were the Leonberger (73%), Irish Wolfhound (69%), Bernese Mountain Dog (69%), Great Dane (68%), Staffordshire Bull Terrier (66%), Rottweiler (65%), Bullterrier (62%), Doberman (62%), Bouvier des Flandres (60%), Airdaleterrier (60%). These data provide information of the combined disease incidence in a large number of different breeds. Breed variations in incidence rate suggests genetic components in disease development. Our study may be valuable in the search for genetic risk‐factors or protective factors.
The Localization of Toll‐like Receptor 2 (TLR2) in the Endometrium and the Cervix of Dogs at Different Stages of the Oestrous Cycle and with Pyometra
Authors: Chotimanukul S , Sirivaidyapong S
Published: December 2012

Content

The aim of this study was to localize and evaluate the role of Toll‐like receptor 2 (TLR2) in the endometrium and cervix of bitches at different stages of the oestrous cycle and in bitches with pyometra. Sixty‐seven nulliparous dogs, ranging in age from 1 to 13 years, were allocated amongst five groups (pro‐oestrus; n = 7, oestrus; n = 10, dioestrus; n = 16, anoestrus; n = 11, pyometra; n = 23). Blood samples were collected for the measurement of progesterone concentration. The mean progesterone concentration was analysed as a parameter for validating the stage of the oestrous cycle in bitches. Tissues collected from uterine horn and cervix were fixed in 4% paraformaldehyde for immunohistochemical examination of TLR2. The expression of TLR2 was assessed semi‐quantitatively. No pathological changes were found in the uterine samples of healthy dogs. In bitches with pyometra, the glandular epithelium expressed TLR2 more intensely than the surface epithelium. The expression of TLR2 in the glandular epithelium was also significantly higher in healthy dogs at oestrus, dioestrus and dogs with pyometra compared with anoestrous dogs (p < 0.01). The expression of TLR2 in the stroma was not observed in the group of healthy dogs at all stages. The surface epithelium of cervix in dogs with pyometra expressed TLR2 significantly more intensely than did the stoma, whereas the expression of TLR2 during oestrus and dioestrus was absent in the stroma of cervix. This study provides the first report of immunohistochemical localization of TLR2 in the canine reproductive tract. In the present study, TLR2 was expressed in endometrial epithelium but was absent in the endometrial stroma of healthy dogs at all oestrous cycle stages. These findings suggest differential expression of TLR in endometrial cells. On the other hand, the lack of TLR2 in the stroma of healthy uteri of dogs may predispose to infection from the invading pathogens once the epithelial cells have been destroyed by the pathogens, especially Gram‐positive bacteria.
Successful Management of Metastatic Transmissible Venereal Tumour to Skin of Mammary Region
Authors: Varughese EE , Singla VK , Ratnakaran U , Gandotra VK
Published: December 2012

Contents

A Dalmatian female presented with a history of vaginal bleeding and was diagnosed as having transmissible venereal tumour (TVT) after cytological examination of the vaginal growth revealed typical TVT cells. A cytology of the aspirate from multiple nodules in the skin near the abdominal and inguinal pair of mammary glands revealed similar cells suggestive of metastasis to skin of mammary region. Chemotherapy was initiated with weekly injections of vincristine sulphate (0.025 mg/kg BW, IV, SID) and haematological examination was performed pre‐ and post‐treatment to assess the prognosis of the patient and side effects of the drug. The major side effects observed during the course of the treatment were high body temperature, mild neutropaenia and significant decrease in packed cell volume, haemoglobin, total leucocyte and erythrocyte count. Four weekly injections of vincristine were administered, and 4 weeks from initiation of treatment, the tumour and nodules were gone, suggesting complete recovery.
Cortisol Profile and Clinical Evaluation of Canine Neonates Exposed Antenatally to Maternal Corticosteroid Treatment
Authors: Vannucchi CI , Regazzi FM , Barbosa MMM , Silva LGC , Veiga GAL , Lúcio CF , Angrimani DS , Nichi M , Furtado PV , Oliveira CA
Published: December 2012

Contents

The effects of glucocorticoids on both foetal canine lung and endogenous serum cortisol concentration have not been clearly delineated. Therefore, we aimed to investigate whether maternal corticosteroid treatment can alter maternal and neonatal cortisol profile and improve neonatal vitality. We allocated six bitches of different breeds and their neonates into two groups: control group (CONT) – maternal administration of saline solution at 55 days post‐ovulation (n = 3); and betamethasone group (BETA) – administration of a single dose of 0.5 mg/kg betamethasone (Celestone Soluspan®) at 55 days post‐ovulation (n = 3). Caesarean sections were scheduled for day 63 after ovulation. However, BETA group dams showed precocious signs of labour, and c‐sections were performed at 58 days post‐ovulation. Maternal and neonatal evaluations were performed periodically between betamethasone administration and birth, respectively. Neonates from both groups presented unsatisfactory (<5) Apgar score at birth. However, in spite of an earlier improvement on vitality found on CONT group and the premature delivery on BETA group, both groups showed acceptable Apgar score 120 min after birth. Neonatal cortisol concentrations were higher on CONT group compared to BETA group at birth. In addition, a gradual decrease on maternal cortisol concentrations was observed in the BETA group from treatment until parturition. These findings suggest that despite the down‐regulation on the hypothalamic‐pituitary‐adrenal axis and the induction of premature delivery, betamethasone treatment was able to provide similar vitality when compared to the untreated neonates born at term.
Lactate in Bitches with Pyometra
Authors: Volpato R , Rodello L , Abibe RB , Lopes MD
Published: December 2012

Contents

Lactate is a compound produced by the anaerobic metabolism of glucose, and hyperlactataemia occurs when the rate of production of lactate exceeds the rate of elimination. This occurs in situations of hypoxia and tissue hypoperfusion. Lactate has been considered a useful prognostic indicator in critically ill patients. Pyometra is a disease of adult female dogs characterized by inflammation of the uterus with an accumulation of exudate, which occurs during the luteal phase. It is one of the most common diseases that occur in the genital tract of female dogs. A total of 31 dogs were diagnosed with pyometra. The diagnosis was confirmed at ultrasonography. Of the 31 dogs, 25 females had open cervix pyometra and six had closed cervix pyometra. Plasma lactate concentrations were determined by an enzymatic colorimetric method. The average concentration (±SD) of plasma lactate in all 31 bitches with pyometra was 3.55 ± 0.46 mm. Healthy dogs had plasma lactate concentrations between 0.3 and 2.5 mm(mean ± SD). Concentrations ranged from 0.8 to 2.9 mmwhen plasma lactate was measured with a portable device and 0.4–2.6 mmwith the blood gas analyser. Even though plasma lactate values vary between several studies and equipment used to measure concentrations, our results for dogs with pyometra are higher indicating hyperlactataemia (Thorneloe et al.,CanVetJ48, 283–288). Plasma lactate in dogs with closed cervix pyometra was mean ± SDand in dogs with open cervix pyometra, it was mean ± SD. The plasma lactate concentration in dogs with pyometra was higher than in healthy bitches, and there was no influence of patency of the cervix on the concentration of plasma lactate concentrations. Plasma lactate concentrations were similar for animals with open and closed pyometra (3.54 ± 0.52 to 3.64 ± 1.03 mm).
Preliminary Study of an Immunochromatography Test for Serological Diagnosis of Canine Brucellosis
Authors: Wanke MM , Cairó F , Rossano M , Laiño M , Baldi PC , Monachesi NE , Comercio EA , Vivot MM
Published: December 2012

Contents

The most widely used screening test for the diagnosis of brucellosis in the dog is the rapid slide agglutination test in the presence of 2‐mercaptoethanol (2ME‐RSAT). The diagnosis is partially confirmed by the agar gel immunodiffusion test (AGID) and definitively confirmed by bacteriological isolation. Some chronic cases not detected by these tests may be detected by ELISA tests. The use of 2ME‐RSAT in routine clinical practice requires a microscope and an experienced operator. An immunochromatographic diagnostic test for canine brucellosis (FASTest® Brucella c., Megacor, Hörbranz, Austria) has been recently released. In this study, we compared the diagnostic performance of the FASTest with those of 2ME‐RSAT, AGID and ELISAs. Sera from 17 healthy dogs used as negative controls yielded negative results by FASTest, indicating a 100% specificity in this sample. Among 27 sera of dogs with acute or subacute brucellosis confirmed by B. canis isolation, all of which were positive by RSAT and ELISAs, the FASTest was positive in 24 cases and AGID in 23. In acute and subacute cases, the sensitivity of FASTest was 89%. Sera from six dogs with bacteriologically confirmed chronic brucellosis, which were positive by ELISAs but negative by 2ME‐RSAT, were also tested; 1 was positive by FASTest and 4 were positive by AGID. These preliminary results indicate a good specificity of the FASTest (100% in this sample) but an unacceptable sensitivity as a screening test. In cases with chronic brucellosis, the sensitivity of the FASTest was lower than that of ELISAs but this assay could make a good intermediate test to be run after a positive RSAT and before running an AGID.
Diagnostic Value of Transcervical Endometrial Biopsies in Domestic Dogs Compared with Full‐Thickness Uterine Sections
Authors: Christensen BW , Schlafer DH , Agnew DW , Wang C , Kozlowski C , Asa CS
Published: December 2012

Contents

Transcervical endometrial biopsy is a useful tool for obtaining information about uterine health in some species. The clinical application of information gained from histopathological interpretations of endometrial biopsies in the bitch has not been validated. We hypothesized that transcervical endometrial biopsy samples would be as diagnostic as full‐thickness uterine sections in identifying cystic endometrial hyperplasia (CEH), inflammation and periglandular fibrosis. Endometrial biopsies were obtained from 20 female adult dogs. Vaginal swabs, gross appearance of the vulva and vaginal tract, and serum progesterone values were used to determine the stage of the oestrous cycle at the time of sampling. The uteri were removed between 1 and 6 days after the biopsy procedure, and full‐thickness sections were collected from each uterine horn and ovary and processed for histopathology. Two pathologists, blinded to the origin of each sample, compared full‐thickness sections from the excised uteri to the biopsy samples collected via the transcervical technique. Pathologic features noted included: CEH, inflammation and periglandular fibrosis. Pathological diagnoses obtained from the biopsy sections were compared with those obtained from the full‐thickness sections, as well as comparing diagnoses between the two pathologists, using McNemar's test. Of the 59 total biopsy samples obtained, 54 were considered diagnostic. All stages of the canine oestrous cycle were represented (anoestrus, proestrus, oestrus and dioestrus). Pyometra was not noted in any of the transcervical biopsy sections, but was noted in many of the full‐thickness sections collected from dogs in dioestrus, suggesting either that biopsy is not a sensitive indicator of pyometra or that the procedure may induce pyometra in dioestrous dogs. Transcervical endometrial biopsy showed similar sensitivity as full‐thickness sections in detecting CEH, inflammation and fibrosis. No differences in describing lesions were detected between pathologists.
Disseminated Transmissible Venereal Tumour Associated With Leishmaniasis in a Dog
Authors: Trevizan JT , Carreira JT , Souza NC , Carvalho IR , Gomes PBC , Lima VMF , Orlandi CMB , Rozza DB , Koivisto MB
Published: December 2012

Contents

This report addresses an atypical transmissible venereal tumour in an 8‐year‐old bitch that was pluriparous and seropositive for leishmaniasis. There were ascites and a serosanguineous discharge from the vulva, but no lesions on the external genital mucosa. An aspirate of the peritoneal fluid showed mononuclear round cells characteristic of transmissible venereal tumour (TVT). Exploratory laparotomy revealed light red, granulomatous structures in the peritoneum, omentum, spleen, liver and uterine horns. Cytological and histopathological tests confirmed the diagnosis of intra‐abdominal TVT. Dissemination of the TVT to several organs inside the abdominal cavity probably resulted from immunosuppression caused by leishmaniasis, which favoured the presence and aggressiveness of TVT.
Research Challenges in Endocrine Aspects of Canine Ovarian Cycles
Authors: Concannon PW
Published: December 2012

Contents

Significant deficiencies exist in understanding factors controlling the nature and timing of critical endocrine changes in canine ovarian cycles. The following merit further study: changes in steroid clearance and binding; mathematically modelling periovulatory hormone rate of change interactions; luteal gonadotropin dependence; endogenous circannual cycles underlying the ovarian cycle; importance of periovulatory follicular steroid dynamics on granulosa and oocytes; in vitro capacity of anoestrous ovarian tissue to demonstrate roles of individual gonadotropins and steroid precursors to increase oestradiol production; factors affecting secretion and activation of the canine female sex pheromone.
The Quantitative Estimation of IT‐Related Risk Probabilities
Authors: Herrmann Andrea
Published: December 2012

How well can people estimate IT‐related risk? Although estimating risk is a fundamental activity in software management and risk is the basis for many decisions, little is known about how well IT‐related risk can be estimated at all. Therefore, we executed a risk estimation experiment with 36 participants. They estimated the probabilities of IT‐related risks and we investigated the effect of the following factors on the quality of the risk estimation: the estimator's age, work experience in computing, (self‐reported) safety awareness and previous experience with this risk, the absolute value of the risk's probability, and the effect of knowing the estimates of the other participants (see: Delphi method). Our main findings are: risk probabilities are difficult to estimate. Younger and inexperienced estimators were not significantly worse than older and more experienced estimators, but the older and more experienced subjects better used the knowledge gained by knowing the other estimators' results. Persons with higher safety awareness tend to overestimate risk probabilities, but can better estimate ordinal ranks of risk probabilities. Previous own experience with a risk leads to an overestimation of its probability (unlike in other fields like medicine or disasters, where experience with a disease leads to more realistic probability estimates and nonexperience to an underestimation).
Risk‐Based Input‐Output Analysis of Influenza Epidemic Consequences on Interdependent Workforce Sectors
Authors: Santos Joost R. , May Larissa , Haimar Amine El
Published: December 2012

Outbreaks of contagious diseases underscore the ever‐looming threat of new epidemics. Compared to other disasters that inflict physical damage to infrastructure systems, epidemics can have more devastating and prolonged impacts on the population. This article investigates the interdependent economic and productivity risks resulting from epidemic‐induced workforce absenteeism. In particular, we develop a dynamic input‐output model capable of generating sector‐disaggregated economic losses based on different magnitudes of workforce disruptions. Anex postanalysis of the 2009 H1N1 pandemic in the national capital region (NCR) reveals the distribution of consequences across different economic sectors. Consequences are categorized into two metrics: (i) economic loss, which measures the magnitude of monetary losses incurred in each sector, and (ii) inoperability, which measures the normalized monetary losses incurred in each sector relative to the total economic output of that sector. For a simulated mild pandemic scenario in NCR, two distinct rankings are generated using the economic loss and inoperability metrics. Results indicate that the majority of the critical sectors ranked according to the economic loss metric comprise of sectors that contribute the most to the NCR's gross domestic product (e.g., federal government enterprises). In contrast, the majority of the critical sectors generated by the inoperability metric include sectors that are involved with epidemic management (e.g., hospitals). Hence, prioritizing sectors for recovery necessitates consideration of the balance between economic loss, inoperability, and other objectives. Although applied specifically to the NCR, the proposed methodology can be customized for other regions.
Metastatic Complications of Bloodstream Infections in Hemodialysis Patients
Authors: Lewis Sarah S. , Sexton Daniel J.
Published: December 2012

Bacteremia is a common infectious complication in hemodialysis patients. Metastatic sites of infection including infective endocarditis, vertebral osteomyelitis, spinal epidural abscess, and septic arthritis occur relatively frequently. These complications are associated with increased morbidity and mortality in hemodialysis patients. Early clinical recognition and appropriate management of these infections are necessary, and strategies to reduce the occurrence of bacteremia in this patient population are warranted.
The Early Modern Kidney—Nephrology in and about the Nineteenth Century (Part 1)
Authors: Eknoyan Garabed
Published: December 2012

The 19th century was a period of momentous scientific discoveries, technological achievements, and societal changes. A beneficiary of these revolutionary upheavals was medical empiricism that supplanted the rationalism of the past giving rise to early modern scientific medicine. Continued reliance on sensory data now magnified by technical advances generated new medical information that could be quantified with increasing precision, verified by repeated experimentation, and validated by statistical analysis. The institutionalization and integration of these methodologies into medical education were a defining step that assured their progress and perpetuation. Major advances were made in the nosography of diseases of the kidney, notably that of the diagnosis of progressive kidney disease from the presence of albuminuria by Richard Bright (1789–1858); and of renal structure and function, notably the demonstration of the continuity of the glomerular capsule with the tubular basement membrane by William Bowman (1816–1892), and the arguments for hemodynamic physical forces mediated glomerular filtration by Carl Ludwig (1816–1895) and for active tubular transport by Rudolf Heidenhain (1834–1897). Improvements in microscopy and tissue processing were instrumental in describing the cellular ultrastructure of the glomerulus and tubular segments, but their integrated function remained to be elucidated. The kidney continued to be considered a tubular secretory organ and its pathology attributed to injury of the interstitium (interstitial nephritis) or tubules (parenchymatous nephritis).
Contributions to Total Phosphorus Intake: All Sources Considered
Authors: Calvo Mona S. , Uribarri Jaime
Published: December 2012

High serum phosphorus is linked to poor health outcome and mortality in chronic kidney disease (CKD) patients before or after the initiation of dialysis. Dietary intake of phosphorus, a major determinant of serum phosphorus, seems to be systematically underestimated using the available software tools and generalized nutrient content databases. Several sources of dietary phosphorus including the addition of phosphorus ingredients in food processing, and phosphorus content of vitamin and mineral supplements and commonly used over‐the‐counter or prescription medications are not fully accounted for by the nutrient content databases and software programs in current clinical use or used in large population studies. In this review, we explore the many unknown sources of phosphorus in the food supply to identify all possible contributors to total phosphorus intake of Americans that have escaped inclusion in past intake estimates. Our goal is to help delineate areas for future interventions that will enable tighter control of dietary phosphorus intake, a critical factor to maintaining health and quality of life in CKD and dialysis patients.
Influence of Temporal Variation in Wall Shear Stress on Intima‐Media Thickening in Arteriovenous Fistulae
Authors: Rajabi‐Jagahrgh Ehsan , Krishnamoorthy Mahesh K. , Wang Yang , Choe Ann , Roy‐Chaudhury Prabir , Banerjee Rupak K.
Published: December 2012

Arteriovenous fistula (AVF) failure is mainly due to venous stenosis characterized by significant amount of intima‐media thickening (IMT), probably in the presence of negative (inward) remodeling. Our hypothesis is that the longitudinal changes in wall shear stress (WSS) within different configurations of AVF can influence remodeling factors (changes in luminal diameter (ΔDh) and IMT) during its maturation process. Dh is an equivalent diameter for a noncircular conduit. A total of six AVFs with curved (C‐AVF; n = 3) and straight (S‐AVF; n = 3) configurations were created between the femoral artery and vein of three pigs, bilaterally. CT scans and ultrasounds were utilized to calculate local WSS at 2D (D: days), 7D, and 28D postsurgery. For each AVF, IMT was measured at four regions along the vein using morphometric analyses. At these regions, repeated measurements of WSS and luminal diameter of each AVF were obtained over time. The ΔDh between 7D and 28D was significantly larger for C‐AVF than for S‐AVF (2.27 ± 0.67 mm vs. 0.02 ± 0.55 mm; p < 0.05). Also, at 28D the amount of IMT in C‐AVF (77.46 ± 7.10 units) was significantly greater (p < 0.05) when compared with S‐AVF (53.71 ± 8.23 units). These structural changes were accompanied by significantly different gradients of WSS over time (τ′) for C‐AVF (−0.56 ± 0.60 dyne/cm2/day) in comparison with S‐AVF (0.71 ± 0.39 dyne/cm2/day). Negative τ′ for C‐AVF corresponded to reduction in WSS level over time resulting in a physiological level of WSS at 28D (4.08 ± 5.08 dyne/cm2). In contrast, a positive τ′ for S‐AVF was associated with the increase in WSS levels over time causing high levels of WSS at 28D (36.68 ± 5.32 dyne/cm2). The decrease in WSS levels for the C‐AVF over time was associated with outward remodeling of the venous wall (favorable to maturation). In contrast, for S‐AVF, the increase in WSS levels over time was associated with inward remodeling and subsequently, venous stenosis. Thus, temporal gradients of WSS, which could be altered by the surgical configuration of AVF, may provide important information on the remodeling behavior of AVFs. Identification of an optimal AVF configuration, which results in a temporal decrease in WSS and an outward remodeling of the venous wall, may reduce AVF maturation failure.
Suicide Risk Protocols: Addressing the Needs of High Risk Youths Identified through Suicide Prevention Efforts and in Clinical Settings
Authors: Heilbron Nicole , Goldston David , Walrath Christine , Rodi Michael , McKeon Richard
Published: December 2012

Several agencies have emphasized the importance of establishing clear protocols or procedures to address the needs of youths who are identified as suicidal through suicide prevention programs or in emergency department settings. What constitutes optimal guidelines for developing and implementing such protocols, however, is unclear. At the request of the Substance Abuse and Mental Health Services Administration, we provide an overview of recommendations, as well as steps taken in conjunction with selected prevention programs and in emergency department settings to address the needs and improve the care of these youths.
Local use of geographic information systems to improve data utilisation and health services: mapping caesarean section coverage in rural Rwanda
Authors: Sudhof Leanna , Amoroso Cheryl , Barebwanuwe Peter , Munyaneza Fabien , Karamaga Adolphe , Zambotti Giovanni , Drobac Peter , Hirschhorn Lisa R.
Published: December 2012

Objectives

To show the utility of combining routinely collected data with geographic location using a Geographic Information System (GIS) in order to facilitate a data‐driven approach to identifying potential gaps in access to emergency obstetric care within a rural Rwandan health district.

Methods

Total expected births in 2009 at sub‐district levels were estimated using community health worker collected population data. Clinical data were extracted from birth registries at eight health centres (HCs) and the district hospital (DH). C‐section rates as a proportion of total expected births were mapped by cell. Peri‐partum foetal mortality rates per facility‐based births, as well as the rate of uterine rupture as an indication for C‐section, were compared between areas of low and high C‐section rates.

Results

The lowest C‐section rates were found in the more remote part of the hospital catchment area. The sector with significantly lower C‐section rates had significantly higher facility‐based peri‐partum foetal mortality and incidence of uterine rupture than the sector with the highest C‐section rates (P < 0.034).

Conclusions

This simple approach for geographic monitoring and evaluation leveraging existing health service and GIS data facilitated evidence‐based decision making and represents a feasible approach to further strengthen local data‐driven decisions for resource allocation and quality improvement.
Innovative newborn health technology for resource‐limited environments
Authors: Thairu L. , Wirth M. , Lunze K.
Published: December 2012

Objectives

To review medical devices addressing newborn health in resource‐poor settings, and to identify existing and potential barriers to their actual and efficient use in these settings.

Methods

We searched Pubmed as our principal electronic reference library and dedicated databases such as Maternova and the Maternal and Neonatal Directed Assessment of Technology. We also researched standard public search engines. Studies and grey literature reports describing devices for use in a low‐ or middle‐income country context were eligible for inclusion.

Results

Few devices are currently described in the peer‐reviewed medical or public health literature. The majority of newborn‐specific devices were found in the grey literature. Most sources described infant warmers, neonatal resuscitators, and phototherapy devices. Other devices address the diagnosis of infectious diseases, monitoring of oxygen saturation, assisted ventilation, prevention of mother‐to‐child transmission of HIV, assisted childbirth, weight or temperature assessment, and others.

Conclusion

Many medical devices designed for newborns in the developing world are under development or in the early stages of production, but the vast majority of them are not available when and where they are needed. Making them available to mothers, newborns, and birth attendants in resource‐limited countries at the time and place of birth will require innovative and creative production, distribution, and implementation approaches.
Sterols and sphingolipids differentially function in trafficking of the Arabidopsis ABCB19 auxin transporter
Authors: Yang Haibing , Richter Gregory L. , Wang Xia , Młodzińska Ewa , Carraro Nicola , Ma Guojie , Jenness Mark , Chao Dai‐yin , Peer Wendy A. , Murphy Angus S.
Published: December 2012

The Arabidopsis ATP‐binding cassette B19 (ABCB19, P‐glycoprotein19) transporter functions coordinately with ABCB1 and PIN1 to motivate long‐distance transport of the phytohormone auxin from the shoot to root apex. ABCB19 exhibits a predominantly apolar plasma membrane (PM) localization and stabilizes PIN1 when the two proteins co‐occur. Biochemical evidence associates ABCB19 and PIN1 with sterol‐ and sphingolipid‐enriched PM fractions. Mutants deficient in structural sterols and sphingolipids exhibit similarity to abcb19 mutants. Sphingolipid‐defective tsc10a mutants and, to a lesser extent, sterol‐deficient cvp1 mutants phenocopy abcb19 mutants. Live imaging studies show that sterols function in trafficking of ABCB19 from the trans‐Golgi network to the PM. Pharmacological or genetic sphingolipid depletion has an even greater impact on ABCB19 PM targeting and interferes with ABCB19 trafficking from the Golgi. Our results also show that sphingolipids function in trafficking associated with compartments marked by the VTI12 syntaxin, and that ABCB19 mediates PIN1 stability in sphingolipid‐containing membranes. The TWD1/FKBP42 co‐chaperone immunophilin is required for exit of ABCB19 from the ER, but ABCB19 interactions with sterols, sphingolipids and PIN1 are spatially distinct from FKBP42 activity at the ER. The accessibility of this system to direct live imaging and biochemical analysis makes it ideal for the modeling and analysis of sterol and sphingolipid regulation of ABCB/P‐glycoprotein transporters.
Antibody‐mediated glycophorin C coligation on K562 cells induces phosphatidylserine exposure and cell death in an atypical apoptotic process
Authors: Wang Duncheng , Seto Eva , Shu Jenny , Micieli Jonathan A. , Fernandes Bernard J. , Denomme Gregory A.
Published: December 2012

Background

Glycophorin C (GPC) is necessary in the maintenance of red blood cell structure. Severe autoimmune hemolytic anemia and hemolytic disease of the fetus and newborn (HDFN) have been associated with Gerbich (Ge) blood group system antigens expressed on GPC. Previous in vitro studies with cord blood progenitor cells have shown that anti‐Ge suppresses erythropoiesis.

Study Design and Methods

Here, we evaluated the K562 erythroleukemic cell line to study the cellular effects of a murine anti‐GPC. Cell proliferation was evaluated after treatment with anti‐GPC. Flow cytometry was used to evaluate exofacial phosphatidylserine (PS) expression and cell viability (propidium iodide binding). Cell morphology was evaluated under light microscopy with cytospin preparations stained with May‐Grünwald Giemsa.

Results

Anti‐GPC dramatically inhibited K562 proliferation and increased PS expression, consistent with cytoplasmic blebbing, suggesting evidence of apoptosis. Z‐VAD‐FMK, an inhibitor of classical apoptosis, was unable to reverse the suppressive effect of anti‐GPC. However, hemin was able to attenuate growth suppression.

Conclusion

Together, the data suggest that anti‐GPC suppresses erythroid proliferation through the induction of nonclassical apoptosis.
The implementation of surface plasmon resonance technique in monitoring pregnancies with expected fetal and neonatal alloimmune thrombocytopenia
Authors: Bakchoul Tamam , Bertrand Gérald , Krautwurst Annika , Kroll Hartmut , Bein Gregor , Sachs Ulrich J. , Santoso Sentot , Kaplan Cécile
Published: December 2012

Background

Maternal anti‐HPA‐1a alloantibodies are responsible for most cases of severe fetal and neonatal alloimmune thrombocytopenia (FNAIT). The presence of HPA‐1a alloantibodies in maternal blood alone does not predict the fetal platelet (PLT) count, and the predictivity of antibody titers determined by enzyme immunoassays (EIAs) is debated. In contrast to EIA, surface plasmon resonance (SPR) provides information on antibody‐binding properties.

Study Design and Methods

Sequential sera from pregnant women with expected FNAIT were assessed for HPA‐1a alloantibodies using SPR. Group I (n = 6) was treated with intravenous immunoglobulin (IVIG) and steroids beginning at 19 weeks of gestation (w.g.), and Group II (n = 4) received intrauterine PLT transfusions (IUT) beginning at 22 w.g. Maternal alloantibodies were quantified using an HPA‐1a monoclonal antibody (MoAb) as a standard. Antibody avidity was determined as the ratio of B700 (end of the dissociation phase) to B350 (end of the association phase); the area under the curve (AUC) was calculated to determine overall antibody binding.

Results

After 22 w.g., alloantibody characteristics remained stable in both groups, while there was a steep decrease in B700 and B350 values between 16 and 22 w.g. (assessed only in Group I), indicating a decrease in anti‐HPA‐1a alloantibody concentrations. Interestingly, the AUCs of the last maternal sample before elective delivery appeared to be correlated with fetal and neonatal PLT counts (p = 0.014 and 0.017, respectively).

Conclusion

SPR provides quantitative information on HPA‐1a alloantibody characteristics in addition to monoclonal antibody–specific immobilization of platelet antigens. SPR results can be calibrated using a MoAb standard and should be further assessed for a potential correlation with fetal PLT count.
A pilot study to assess the hemostatic function of pathogen‐reduced platelets in patients with thrombocytopenia
Authors: Johansson Pär I. , Simonsen Anne Catrine , Brown Peter N. , Ostrowski Sisse R. , Deberdt Liesbeth , Van Hoydonck Pascale , Yonemura Susan S. , Goodrich Raymond P.
Published: December 2012

Background

Platelet (PLT) support is critical to the care of patients with thrombocytopenia, but allogeneic transfusions carry risk. Pathogen reduction mitigates some transfusion risks, but effects on PLT function remain a concern. This clinical pilot study assessed the effect of pathogen reduction technology with riboflavin plus ultraviolet light using thrombelastography (TEG).

Study Design and Methods

This prospective, randomized, crossover study compared Mirasol‐treated (MIR) and standard reference (REF) PLT transfusions. PLT counts and TEG measurements were taken at pretransfusion and 1‐ and 24‐hour‐posttransfusion time points. The primary outcome measure was the pretransfusion to 1‐hour‐posttransfusion change in maximum amplitude (ΔMA1hr). Secondary endpoints included ΔMA among other time points, relative MA, and the PLT count–MA correlation.

Results

Of 16 enrolled patients, one withdrew before study treatment and three did not require two transfusions, leaving 12 patients in the efficacy analyses (seven MIR‐REF, five REF‐MIR). ΔMA1hr (mean ± SD) was 10.60 ± 6.47 mm for MIR and 14.33 ± 5.38 mm for REF (p = 0.20, n = 10). ΔMA24hr was 9.49 ± 7.94 for MIR and 7.13 ± 3.08 for REF (p = 0.38, n = 9); ΔMA24hr‐1hr was −1.11 ± 2.95 for MIR and −7.20 ± 4.81 for REF (p = 0.016, n = 8). MA values for MIR and REF correlated with the log of PLT count (rMIR = 0.6901, rREF = 0.7399).

Conclusion

TEG is sensitive to changes in hemostatic function resulting from a single PLT transfusion. MIR and REF provided similar increments in hemostatic function in the immediate posttransfusion period and at 24 hours. A significant difference detected for ΔMA24hr‐1hr suggests different PLT clearance mechanisms. The relationship of these variables to clinically meaningful outcomes, for example, bleeding events or transfusion requirements, has yet to be determined.
Motivational differences between whole blood and plasma donors already exist before their first donation experience
Authors: Veldhuizen Ingrid , van Dongen Anne
Published: December 2012

Background

The demand for plasma products has increased rapidly. It is therefore important to understand donating behavior by plasma donors. This study investigates whether motivational differences between whole blood and plasma donors already exist at the beginning of a donor career.

Study Design and Methods

New donors (n = 4861) were invited to fill out a questionnaire before their first donation (response, 61%). The questionnaire assessed variables from the Theory of Planned Behavior (intention, self‐efficacy, attitude, and norms), conscientiousness, and donation anxiety. Three years later it was determined who became whole blood or plasma donor. Multivariable linear regression analyses for intention were fitted separately for whole blood and plasma donors. A logistic regression analysis was executed to estimate the effect of intention at the beginning of a donor career on becoming a plasma donor.

Results

Plasma donors had a higher intention, self‐efficacy, attitude, and conscientiousness and a lower anxiety than whole blood donors. In plasma and whole blood donors, both self‐efficacy and cognitive attitude were positively related to intention but with different strength (plasma, β = 0.47 and β = 0.30; whole blood, β = 0.57 and β = 0.17). Having a high level of intention increased the odds of becoming a plasma donor (odds ratio, 1.33; 95% confidence interval, 1.12‐1.59).

Conclusion

Motivational differences already exist between future whole blood and plasma donors before their first donation. Although a feeling of self‐efficacy is necessary for all new donors, more favorable cognitions are important for future plasma donors. Recruitment strategies for plasma donors should focus on attracting the more self‐confident donors by highlighting the usefulness of plasma donation.
Blood utilization in patients with burn injury and association with clinical outcomes (CME)
Authors: Lu Rommel P. , Lin Feng‐Chang , Ortiz‐Pujols Shiara M. , Adams Sasha D. , Whinna Herbert C. , Cairns Bruce A. , Key Nigel S.
Published: December 2012

Background

Uncontrolled bleeding is an important cause of increased transfusion in burn victims; however, description of blood utilization patterns in the burn population is lacking.

Study Design and Methods

We conducted a single‐institution, retrospective cohort study to measure blood utilization in 89 consecutive burn patients with 15% to 65% total body surface area (TBSA) burn within 60 days of injury. We also evaluated the relationship of blood product utilization with clinical variables including anticoagulant usage and mortality.

Results

We determined that: 1) the predictors for increased red blood cells (RBCs) and plasma transfusions were high TBSA burn and the use of argatroban anticoagulation (for suspected heparin‐induced thrombocytopenia [HIT]); 2) TBSA burn and patient age were independent predictors of mortality, but not RBC or plasma transfusion; and 3) the incidence of symptomatic venous thromboembolic events is not uncommon (11.2%), although HIT is rare (1.1%).

Conclusion

Despite concerns about adverse correlation between increased number of transfusions and mortality in other clinical settings, we did not find this association in our study. However, we demonstrated that the type and intensity of anticoagulation carries substantial risk for increased RBC as well as plasma usage.
Neural circulatory control during exercise: early insights
Authors: Mitchell Jere H.
Published: December 2012

New Findings

What is the topic of this lecture?

Sir William Paton, a distinguished physician scientist, was interested in the origins of concepts in physiology. This lecture explores the early insights on the neural control of the circulation during exercise.

What advances does it highlight?

This lecture presents some of the outstanding seminal investigations on the central and peripheral control mechanisms that regulate the autonomic neural activity to the heart and blood vessels during exercise.

During exercise, the cardiovascular response is rapidly and appropriately matched to the intensity of the physical activity. The autonomic nervous system plays an important role in achieving this closely matched circulatory response by an increase in the sympathetic nerve activity to the heart, blood vessels and adrenal medulla and a decrease in the parasympathetic nerve activity to the heart. Early insights into the mechanisms that controlled these cardiovascular changes during exercise were reported in the 19th century. At that time, two mechanisms were hypothesized to be responsible for these changes. In one mechanism, a signal arising in a central area of the brain causes a parallel activation of skeletal muscle contraction and of autonomic nervous system changes (now termed ‘central command’). In the other mechanism, a signal arising in the contracting skeletal muscle causes a reflex activation of the autonomic nervous system changes (now termed ‘exercise pressor reflex’). Some important investigators involved in early studies include Johan Johansson, August Krogh, Johannes Lindhard and Horace Smirk. Also, Florence Buchanan and Louis Fridericia should be recognized for their contributions. In more recent years, the important involvement of a third mechanism, the arterial baroreflex, has been elucidated. Since those early insights, experiments in both animals and humans have added important findings that strongly support these early hypotheses.
Utility of PCR in Diagnosis of Invasive Fungal Infections: Real-Life Data from a Multicenter Study
Authors: Lass-Flörl Cornelia , Mutschlechner Wolfgang , Aigner Maria , Grif Katharina , Marth Claudia , Girschikofsky Michael , Grander Wilhelm , Greil Richard , Russ Gudrun , Cerkl Peter , Eller Mirjam , Kropshofer Gabriele , Eschertzhuber Stephan , Kathrein Hermann , Schmid Stefan , Beer Ronny , Lorenz Ingo , Theurl Igor , Nachbaur David
Published: December 2012

Prospective studies addressing the clinical value of broad-range PCR using the internal transcribed spacer region (ITS) for diagnosis of microscopy-negative fungal infections in nonselected patient populations are lacking. We first assessed the diagnostic performance of ITS rRNA gene PCR compared with that of routine microscopic immunofluorescence examination. Second, we addressed prospectively the impact and clinical value of broad-range PCR for the diagnosis of infections using samples that tested negative by routine microscopy; the corresponding patients' data were evaluated by detailed medical record reviews. Results from 371 specimens showed a high concordance of >80% for broad-range PCR and routine conventional methods, indicating that the diagnostic performance of PCR for fungal infections is comparable to that of microscopy, which is currently considered part of the “gold standard.” In this prospective study, 206 specimens with a negative result on routine microscopy were analyzed with PCR, and patients' clinical data were reviewed according to the criteria of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. We found that broad-range PCR showed a sensitivity, specificity, positive predictive value, and negative predictive value of 57.1%, 97.0%, 80%, and 91.7%, respectively, for microscopy-negative fungal infections. This study defines a possible helpful role of broad-range PCR for diagnosis of microscopy-negative fungal infections in conjunction with other tests.
ORF9p Phosphorylation by ORF47p Is Crucial for the Formation and Egress of Varicella-Zoster Virus Viral Particles
Authors: Riva Laura , Thiry Marc , Bontems Sebastien , Joris Aline , Piette Jacques , Lebrun Marielle , Sadzot-Delvaux Catherine
Published: December 2012

The role of the tegument during the herpesvirus lytic cycle is still not clearly established, particularly at the late phase of infection, when the newly produced viral particles need to be fully assembled before being released from the infected cell. The varicella-zoster virus (VZV) protein coded by open reading frame (ORF) 9 (ORF9p) is an essential tegument protein, and, even though its mRNA is the most expressed during the productive infection, little is known about its functions. Using a GalK positive/negative selection technique, we modified a bacterial artificial chromosome (BAC) containing the complete VZV genome to create viruses expressing mutant versions of ORF9p. We showed that ORF9p is hyperphosphorylated during the infection, especially through its interaction with the viral Ser/Thr kinase ORF47p; we identified a consensus site within ORF9p recognized by ORF47p and demonstrated its importance for ORF9p phosphorylation. Strikingly, an ultrastructural analysis revealed that the mutation of this consensus site (glutamate 85 to arginine) strongly affects viral assembly and release, reproducing the ORF47 kinase-dead VZV phenotype. It also slightly diminishes the infectivity toward immature dendritic cells. Taken together, our results identify ORF9p as a new viral substrate of ORF47p and suggest a determinant role of this phosphorylation for viral infectivity, especially during the process of viral particle formation and egress.
Massive haematuria successfully managed by intravesical ankaferd in a haemodialysis patient complicated with disseminated intravascular coagulation
Authors: Solak Yalcin , Gaipov Abduzhappar , Ozbek Orhan , Hassan Mustafa Aziz , Yeksan Mehdi
Published: December 2012

Massive haematuria is a life-threatening condition, demanding immediate management of bleeding. The mortality is very high in the case of delayed management of bleeding, especially in elderly patients with concomitant comorbidity. The treatment options of haematuria are wide, and depend on underlying conditions. However, therapeutic choices are limited in the presence of massive and intractable haematuria caused by disseminated intravascular coagulation (DIC). Ankaferd blood stopper (ABS) is a novel, commercially available, haemostatic agent, which has been approved by the Ministry of Health for local use in Turkey. Here, for the first time in the literature, we report a case of diffuse intravesical bleeding stopped by intravesical use of ABS in a 72-year-old man, haemodialysis patient complicated with sepsis and DIC.
Successful conservative management of ectopic pregnancy in caesarean section scar
Authors: Al-Hashimi Sara , Maiti Sachchidananda , Macfoy Donald
Published: December 2012

Caesarean scar pregnancy is a rare type of ectopic pregnancy. The authors present a 24-year-old woman 5 weeks after her last menstrual period. She had a history of a single caesarean section which was followed by a normal vaginal delivery. Ultrasound imaging revealed a pregnancy in her lower segment caesarean section scar. The decision on the choice of treatment was influenced mainly by the β-human chorionic gonadotropin levels in the patient's blood. Although a few reports have been published on similar cases, spontaneous resolution of a caesarean scar ectopic pregnancy of less than 5 weeks gestation is yet to be reported. The patient is now asymptomatic and her urine pregnancy test has been confirmed negative.