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Vascular calcification is associated with cardiovascular disease, the most common cause of death in chronic kidney disease (CKD). Patients with CKD are treated with vitamin D receptor activators (VDRAs); therefore, we determined if this treatment affects vascular calcification. Uremic rats were given vehicle, calcitriol, paricalcitol, or doxercalciferol three times a week for 1 month. Calcitriol significantly increased the serum calcium–phosphate product and aortic calcium content. Paricalcitol had no effect but the same dose of doxercalciferol significantly increased the calcium–phosphate product and the aortic calcium content, the latter being confirmed by von Kossa staining. To see if the increased aortic calcium was due to an increased serum calcium–phosphate product or to a differential effect of the two VDRAs, we lowered the dose of doxercalciferol and increased the dose of paricalcitol. A lower doxercalciferol did not increase the calcium–phosphate product but increased the aortic calcium content. A higher dose of paricalcitol still had no effect. Doxercalciferol treatment increased the mRNA and protein expression of the bone-related markers Runx2 and osteocalcin in the aorta, whereas paricalcitol did not. Hence, different VDRAs have different effects on vascular calcification in uremic rats. The effects are independent of the serum calcium–phosphate product suggesting independent mechanisms.Kidney International (2007) 72, 709–715; doi:10.1038/sj.ki.5002406; published online 27 June 2007 [ABSTRACT FROM AUTHOR]

Ebola viral disease (EVD) is a highly infectious and potentially fatal illness with a case fatality rate ranging from 25% to 90%. To effectively control its spread, there is a need for rapid, reliable and lowcost point-of-care (P OC) diagnostic tests. While various EVD diagnostic tests exist, few are P OC tests, and many are not cost-effective. The use of antibodies in these tests has limitations, prompting the exploration of aptamers as potential alternatives. Various proteins from the Ebola virus (EBOV) proteome, including EBOV nucleoprotein (NP), are considered viable targets for diagnostic assays. A previous study identified three aptamers (Apt1. Apt2 and Apt3) with high affinity for EBOV NP using systemic evolution of ligands by exponential enrichment (SELEX). This study aimed to employ in silico methods, such as Phyre2, RNAfold, RNAComposer, HADDOCK and GROMACS, to model the structures of EBOV NP and the aptamers, and to investigate their binding. The in silico analysis revealed successful binding of all the three aptamers to EBOV NP, with a suggested ranking of Apt1 > Apt2 > Apt3 based on binding affinity. Microscale thermophoresis (MST) analysis confirmed the binding, providing dissociation constants of 25 ± 2.84, 56 ± 2.76 and 140 ±3.69 nM for Apt1, Apt2 and Apt3, respectively. The study shows that the findings of the in silico analysis was in agreement with the MST analysis. Inclusion of these in silico approaches in diagnostic assay development can expedite the selection of candidate aptamers, potentially overcoming challenges associated with aptamer application in diagnostics.Communicated by Ramaswamy H. Sarma.

Feline breeding colonies are important to the feline industry by preserving traits desirable for a particular breed or in research settings by maintaining medically valuable genetic traits. As breeding females age, their reproductive efficiency declines. The objective of this study was to determine the most common causes of infertility in breeding females that were producing fewer kittens. Knowing the cause and average age of infertility would allow management decisions to be made for the betterment of the colony. The medical records of 70 queens retired from breeding from a single research colony were examined for litter size and number, fertility over their lifespan, and age and reason for removal from breeding stock. Sections of uterus and ovaries were evaluated using gross and histopathological examination for a subset of these queens (46). The data suggests that mature, continuously breeding female cats may show signs of reduced fertility (infertile matings or reduced litter size) as early as 3 years of age and may be a result of undiagnosed Cystic Endometrial Hyperplasia (CEH), endometritis, pyometra and/or ovarian cysts. Evaluation of breeding queens should include periodic ultrasounds to monitor for ovarian cysts and evidence of CEH. Retiring animals from breeding once signs of infertility become apparent is recommended., (Published by Elsevier Inc.)

Background: Rheumatic fever is a preventable chronic disease preceded by group A beta-haemolytic streptococcal (GABHS) pharyngitis., Objective: To test the non-inferiority of once-daily (QD) oral amoxicillin to the recommended twice-daily (BID) oral penicillin V in GABHS pharyngitis., Methods: This was a randomised non-inferiority trial carried out in a school-based clinic in New Zealand. Children presenting with GABHS pharyngitis were randomised to oral amoxicillin 1500 mg QD (or 750 mg if bodyweight was

The application of the NMR-MObile Universal Surface Explorer (NMR-MOUSE) to study food systems is evaluated using oil-in-water emulsions, and the results are compared to those obtained using a conventional low-field NMR (LF-NMR) instrument. The NMR-MOUSE is a small and portable LF-NMR system with a one-sided magnet layout that is used to replace the conventional magnet and probe on a LF-NMR instrument. The high magnetic field gradients associated with the one-sided MOUSE magnet result in NMR signal decays being dominated by molecular diffusion effects, which makes it possible to discriminate between the NMR signals from oil and water. Different data acquisition parameters as well as different approaches to the analysis of the NMR data from a range of oil-in-water emulsions are evaluated, and it is demonstrated how the concentration of oil and water can be determined from the NMR-MOUSE signals. From these model systems it is concluded that the NMR-MOUSE has good potential for the quantitative analysis of intact food products.

Over the past 15 years, MR imaging of the abdomen and pelvis has progressed significantly. Although initially found to be useful as an adjunct to CT imaging for selective applications, MR imaging now is establishing a role as a primary diagnostic technique. Increasing evidence shows that MR imaging has advantages over CT regarding diagnostic sensitivity and specificity for many abnormalities of solid organs, bile and pancreatic ducts, bowel, peritoneum, and retroperitoneum. This article discusses and contrasts current MR and CT techniques for imaging the liver and discusses the relative ability to identify and diagnose focal liver disease.

Using a multitechnique approach, two temperature domains have been identified in agarose gelation. Below 35 degrees C, fast gelation results in strong, homogeneous and weakly turbid networks. The correlation length, evaluated from the wavelength dependence of the turbidity, is close to values of pore size reported in the literature. Above 35 degrees C, gelation is much slower and is associated with the formation of large-scale heterogeneities that can be monitored by a marked change in the wavelength dependence of turbidity and visualised by transmission electron microscopy. Curing agarose gels at temperatures above 35 degrees C, and then cooling them to 20 degrees C, produces much weaker gels than those formed directly at 20 degrees C. Dramatic reductions in the elastic modulus and failure strain and stress are found in this case as a result of demixing during cure. An interpretation, based on the kinetic competition between osmotic forces (in favor of phase separation) and elastic forces (that prevent it) is proposed., (Copyright 2001 John Wiley & Sons, Inc.)

Several studies have determined that growth factors, including hepatocyte growth factor (HGF), have a crucial role in the regenerative process of renal tubules after ischemic or toxic insult. Recent research has ascertained that as well as necrotic cell death, there is evidence of apoptosis after an acute renal injury. We attempted to determine the effect of HGF on apoptosis after ischemic renal injury in rats. We administered HGF or vehicle to 12 rats after ischemic insult and compared them with 6 sham-operated controls. Rats were killed at 48 hours, and histopathologic assessments were performed on the renal tissue. The microscale autoradiographic method was used for qualitative analysis of DNA fragmentation. This method was chosen over the widely used ethidium bromide-staining method because it increases the sensitivity of detection of apoptotic DNA. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling histopathologic staining was used to identify apoptosis in situ. Apoptotic changes were clearly shown by electron microscopy in vehicle-treated animals. Despite showing profound evidence of tubular necrosis, apoptotic changes were markedly reduced in HGF-treated animals compared with vehicle-treated animals. DNA-laddering analysis further confirmed the antiapoptotic effect of HGF. To our knowledge, this is the first in vivo illustration of the inhibitory activity of a growth factor on apoptosis in the setting of tubular necrosis. The role of apoptosis in the setting of acute renal failure has not been elucidated; thus, additional research is necessary to determine the significance of these findings.

Introduction: Recent changes by the Health Care Financing Administration (HCFA) have resulted in decreased Medicare support for emergency medicine (EM) residencies., Objective: To determine the effects of reduced graduate medical education (GME) funding support on residency size, resident rotations, and support for a fourth postgraduate year (PGY) of training and for residents with previous training., Methods: A 36-question survey was developed by the Council of Emergency Medicine Residency Directors (CORD) committee on GME funding and sent to all 122 EM program directors (PDs). Responses were collected by the Society for Academic Emergency Medicine (SAEM) office and blinded with respect to the institution., Results: Of 122 programs, 109 (89%) responded, of which 78 were PGY 1-3 programs, 19 were PGY 2-4, and 12 were PGY 1-4. The PDs were asked specifically whether there were changes in program size due to changes in Medicare reimbursement. Although few programs (12%) decreased their size or planned to decrease their size, 39% had discussions regarding decreasing their size. Thirty percent of the PDs responded that other programs at their institution had already decreased their size; 26% of the PDs had problems with financing outside rotations; and 24% had a decrease in off-service residents in their emergency departments (EDs). Only seven (6%) of programs paid residents from practice plan dollars, while most (82%) were fully supported by federal GME funding. Nearly all four-year programs (97%) received full resident salary support from their institutions and 77% of programs accept residents with previous training., Conclusions: Nearly all EM programs are fully supported by their institutions, including the fourth postgraduate year. Most programs take residents with previous training. Although few programs have reduced their size, many are discussing this. Many programs have had difficulty with funding off-service rotations and many have had decreased numbers of off-service residents in their EDs. Recent GME funding changes have had adverse effects on EM residency programs.

Study Objective: Flexion-extension (F/E) radiographs of the cervical spine are often used in patients with blunt trauma when the evaluating physician remains concerned about bony or ligamentous injuries despite negative or nondiagnostic standard radiographs. The use of this approach has never been addressed in a large prospective study. We sought to determine the clinical factors associated with ordering F/E views and the incidence of diagnostic F/E films in patients with a normal 3-view cervical spine series., Methods: Patients with blunt trauma selected for radiographic cervical spine imaging at 21 participating institutions in the National Emergency X-Radiography Utilization Study project underwent standard 3-view (cross-table lateral, anteroposterior, and odontoid views) series, as well as any other imaging deemed necessary by their physicians. Injuries detected by means of screening radiography were then compared with final injury status for each patient, as determined by review of all radiographic studies. Patients who underwent F/E views were analyzed separately., Results: Of 818 patients ultimately found to have cervical spine injury, 86 (10.5%) underwent F/E testing. Two patients sustained stable bony injuries detected only on F/E views. Four other patients had a subluxation detected only on F/E views, but all had other injuries apparent on routine cervical spine imaging., Conclusion: F/E imaging adds little to the acute evaluation of patients with blunt trauma. Other approaches, including magnetic resonance imaging, computed tomography, or delayed F/E, in the presence of specific clinical concerns would seem to provide a more reasonable approach to adjunctive imaging.

The purpose of this study was to evaluate the relationship between renal corticomedullary differentiation (CMD) on MR imaging and serum creatinine (sCr) level in patients with acute renal failure (ARF). Twenty-one patients with ARF were retrospectively investigated. In all 21 patients, sCr levels were obtained on the same date as the MR study, and within 8 days before and after the MR study. CMD was assessed on non-contrast T(1)-weighted images and immediate post-gadolinium spoiled gradient echo (Gd-SGE) images. Presence of CMD was graded into 3 groups as 'preserved', 'intermediate', or 'loss'. On non-contrast T(1)-weighted images, 12/21 (57%) showed loss of CMD and 9/21 (43%) showed preserved CMD. On immediate Gd-SGE images, 5/21 (24%) showed loss of CMD, 12/21 (57%) preserved CMD, and 4/21 (19%) intermediate CMD. The sCr levels of 9 patients with preserved CMD on non-contrast T(1)-weighted images ranged from 1.4 to 10.5 mg/dl (mean 4.6 mg/dl), while those of 12 patients with loss of CMD ranged from 1.6 to 7.6 mg/dl (mean 4.8 mg/dl), which was not statistically significant (p > 0.2). Renal CMD can remain preserved on non-contrast T(1)-weighted or immediate Gd-SGE images in patients with acute presentation of ARF, independent of sCr level.

MR imaging of the pancreas has evolved with better understanding of pathologic and radiologic correlation and with continued improvement in rapid-acquisition breath-hold or breathing-independent MR imaging techniques. MR imaging should be considered essential in the evaluation of pancreatic disease and particularly for optimal presurgical detection, characterization, and staging of pancreatic masses.

The enzyme, poly(ADP-ribose) polymerase (PARP), effects repair of DNA after ischemia-reperfusion (I/R) injury to cells in nerve and muscle tissue. However, its activation in severely damaged cells can lead to ATP depletion and death. We show that PARP expression is enhanced in damaged renal proximal tubules beginning at 6-12 h after I/R injury. Intraperitoneal administration of PARP inhibitors, benzamide or 3-amino benzamide, after I/R injury accelerates the recovery of normal renal function, as assessed by monitoring the levels of plasma creatinine and blood urea nitrogen during 6 days postischemia. PARP inhibition leads to increased cell proliferation at 1 day postinjury as assessed by proliferating cell nuclear antigen and improves the histopathological appearance of kidneys examined at 7 days postinjury. Furthermore, inhibition of PARP increases levels of ATP measured at 24 h postischemia compared with those in vehicle-treated animals. Our data indicate that PARP activation is a part of the cascade of molecular events that occurs after I/R injury in the kidney. Although caution is advised, transient inhibition of PARP postischemia may constitute a novel therapy for acute renal failure.

De novo CD44 and ligand expression at wound margins accompanies cellular proliferation and migration that effect repair of injured mucosal and vascular endothelial tissues. To determine whether CD44 could play a role in recovery from acute ischemic renal injury, we characterized its renal expression and those of two of its ligands, hyaluronic acid and osteopontin. Although no expression is detectable in nonischemic kidneys, several mRNAs for CD44 are present within 1 day after injury. CD44 mRNA is expressed in proximal tubules undergoing repair. CD44 peptide is present in basal and lateral cell membranes. Hyaluronic acid is normally expressed in the interstitium of the renal papilla only. By 1 day postischemia, hyaluronic acid can be detected, in addition, in the interstitium surrounding regenerating tubules. Osteopontin, not normally expressed in the renal proximal tubule, is expressed in regenerating tubules by 3 days after induction of acute ischemic injury. Immunoreactive osteopontin peptide continues to be localized in those tubules still undergoing repair for as long as 7 days after the injury. Our data are consistent with a role for CD44-ligand interactions in the regenerating proximal tubule participating in the process of recovery after ischemic injury.

Serum opacity factor (SOF) is produced by group A streptococci belonging to certain M types. SOF cleaves the apolipoprotein component of the high density lipoprotein fraction of serum rendering it insoluble which in turn leads to serum opacity. SfbII protein, a fibronectin binding surface protein cloned from group A streptococci, was obtained from a strain of M75. Here we show that this protein has a second functional domain responsible for SOF activity. The fibronectin binding region was located in the C-terminal end of the protein. Deletion analysis showed that the remainder of the protein was required for SOF activity. Sequence analysis of SfbII, when compared with the published sequence of SOF22, showed 99% identity with a difference of only four amino acids. In spite of this high homology, SOF from M75 was type-specific and antibody evoked specifically inhibited only SOF produced by M75. Antibodies found in human serum following natural infection also inhibited the SOF of SfbII in a type-specific manner. The results showed that the SfbII protein from M75 is SOF with a high serotype-specific enzyme activity.

A previously healthy 42-year-old man presented to the emergency department with progressive weakness, lightheadedness, nausea, and lower extremity edema. Evaluation revealed hypotension, pulsus paradoxus, leukocytosis, hepatic and renal dysfunction, and an air-fluid level in the mediastinum. Emergency department ultrasound confirmed the presence of a large pericardial fluid collection. The patient was admitted to the medical intensive care unit with a diagnosis of pyopneumopericardium for emergent pericardiocentesis.

Aims: To review the prevalence of antibiotic resistance and the distribution of capsular types among pneumococci from invasive disease in New Zealand from 1995 through 1997., Method: Pneumococci isolated from sterile sites that were referred to the Institute of Environmental Science and Research (ESR) were tested for antimicrobial susceptibility and capsular type., Results: A total of 994 pneumococci were referred by 27 hospital and community laboratories. Almost 74% of the isolates were from patients aged < 15 years or > or = 60 years. The majority (88.2%) of the isolates were from blood cultures. In 1997, cefotaxime-resistant pneumococci were confirmed for the first time from invasive disease in New Zealand. Over the three years, 6.0% of the pneumococci were penicillin-nonsusceptible (MIC > or = 0.12 mg/L) and 3.7% were cefotaxime-nonsusceptible (MIC > or = 1 mg/L). Penicillin nonsusceptibility increased significantly from 1.9% in 1995 to 6.2% in 1996 and 9.9% in 1997. Similarly, cefotaxime nonsusceptibility increased from 0.6% in 1995 to 3.5% in 1996 and 6.9% in 1997. In descending order of frequency, the ten most common capsular types were 14, 19, 6, 9, 1, 4, 18, 7, 23, and 3. Eighty-three percent of the penicillin-nonsusceptible pneumococci belonged to serotypes 9V, 19A, 19F, 23F, 14 and 6B and 90% belonged to serotypes included in the 23-valent vaccine., Conclusions: The increasing prevalence of antimicrobial resistance among pneumococci highlights the need for continued surveillance and for effective measures to prevent pneumococcal infections.

In the last decade, percutaneous angioplasty (PTA) has been used with increasing frequency to treat infrainguinal atherosclerotic lesions. In hopes of better delineating the role of PTA, we undertook a retrospective analysis of infrainguinal PTA in one hospital over a 7-year period. The charts of all patients receiving infrainguinal PTA from 1989 to 1996 were reviewed. Demographics, site and type of lesion, and results of treatment were recorded. Survival curves were plotted using the Kaplan-Meier method following current Society of Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) guidelines. Differences in times to first failure were tested using the log rank method. Failures were documented by duplex ultrasound. All patients requiring repeat intervention underwent contrast angiography. In selected patients with stenotic lesions <3 cm, infrainguinal PTA may be an appropriate initial treatment modality. However, 5-year patency rates are significantly lower than those achieved by saphenous vein grafting. The efficacy of the procedure is markedly decreased when used to treat arterial stenoses >3 cm in length as well as occlusions, and surgical revascularization may be a more appropriate initial therapeutic procedure.

Study Objective: Pneumococcal vaccination (PV) rates for eligible emergency department patients are less than 25%. This study determines the potential effect of an ED-based pneumococcal vaccination program in preventing pneumococcal bacteremia (PB) in high-risk patients., Methods: In a retrospective observational study, hospital records of 188 consecutive adults (>/=18 years old) with PB were reviewed to determine how many were treated in the ED from 1 to 72 months before their admission for bacteremia. Potential cost savings and mortality reductions from an ED-based PV program were calculated assuming PV prevents 65% of bacteremic episodes. A retrospective review of 10,650 ED charts determined the percentage of patients with PV indications and the relative frequency of indications., Results: One hundred four (55%) of the 188 patients with PB were seen in the ED less than or equal to 72 months before their admission for PB, and 91 (88%) of the 104 had indications for PV. These 91 patients had been evaluated in the ED an average of 3.4 times per patient during this 72-month period. Nine patients (10%) died before discharge. Mean hospital stay for the 82 survivors was 11.2 days. Of 10,650 ED charts reviewed, 2,011 (19%) had documented PV indications. Most prevalent PV indications were age 65 years or older (851 patients, 42%), diabetes mellitus (697, 35%), malignancy (248, 12%), chronic renal failure (228, 11%), and immunosuppression (221, 11%). Estimated cost savings ranged from $168,940 to $427,380., Conclusion: ED-based PV programs would result in considerable cost savings and decreased mortality.

The renal expression of transforming growth factor-beta1 (TGF-beta1) is enhanced following induction of ischemic injury in rat. In cultured renal cells, TGF-beta stimulates the synthesis of extracellular matrix. To link TGF-beta1 expression with the regulation of extracellular matrix postischemia, we characterized the expression of several genes known to regulate extracellular matrix synthesis at various times during recovery from acute ischemic renal injury in rat. Levels of mRNA for plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor of metalloprotease-1 (TIMP-1), alpha1(IV) collagen, and fibronectin-EIIIA (FN-EIIIA) mRNAs were significantly enhanced in kidneys within 12 h to 3 days after injury and remained elevated at 7-28 days postischemia relative to levels in kidneys of sham-operated controls. PAI-1 mRNA and peptide were localized in regenerating proximal tubules at 3 and 7 days postischemic injury. alpha1(IV) Collagen and FN-EIIIA mRNAs were expressed primarily in regenerating proximal tubule cells. Immunoreactivity for FN-EIIIA was enhanced in the tubular basement membrane (TBM) of regenerating proximal tubules, and alpha1(IV) collagen immunoreactivity was detected in thickened tubulointerstitial spaces. In contrast, TIMP-1 immunoreactivity was enhanced in distal nephron structures postischemia. Immunoneutralization of TGF-beta in vivo attenuated the increases in FN-EIIIA, alpha1(IV) collagen, PAI-1, and TIMP-1 mRNAs by 52%, 73%, 43%, and 27%, respectively. These data are consistent with TGF-beta expression postischemic injury participating in renal regeneration of extracellular matrix homeostasis in the proximal TBM.

Quantitative estimates are important to establish whether pork adulteration in ground beef is accidental or intentional. A standard agar gel radial immunodiffusion (RID) test using forensic-grade antiserum to porcine albumin and an enzyme-linked immunosorbent assay (ELISA) using forensic-grade anti-porcine glycoprotein immunoglobulin were used to determine from 1 to 75% raw pork in raw ground beef. The RID test, which incorporated 1.5% anti-pork serum in 1% immunodiffusion agar, formed precipitin rings with pork albumin in agar wells. A linear standard curve was obtained by plotting the diffusion area against standard pork concentrations ranging from 0 to 80%. For the ELISA the endpoint optical density increased linearly versus log % pork between 0.0625% and 2% pork. In spiked samples, the RID test had a detection limit of 3 to 5%, a coefficient of variation (CV) of 22%, and a recovery of 105%. The ELISA had a detection limit of 1%, a CV of 18%, and a recovery of 114%. The mean recovery from the spiked samples by the ELISA and RID test was not significantly different (P > 0.05) from the known sample amounts. Quantitation by RID of 28 ground beef samples (27 of which were DTEK ELISA-positive for pork adulteration) revealed a wide range of pork content, with values as high as 48%.

Leptin is an adipocyte-secreted hormone that has effects on appetite and energy expenditure. Several studies have shown that end-stage renal disease results in elevated plasma leptin concentrations and that the kidney is responsible for most of leptin elimination in rodents. Leptin metabolism was investigated in rats that underwent unilateral nephrectomy to experimentally limit renal elimination function. Within 4 h of nephrectomy, plasma leptin concentrations increased from 2.9 +/- 0.8 to 5.8 +/- 1.0 & microg/l but thereafter rapidly (<24 h) decreased to prenephrectomy concentrations, despite continued elevated plasma creatinine levels. Sham-operated rats maintained presurgical concentrations of leptin and creatinine throughout the experiment. Kinetic studies of 125I-labeled leptin elimination showed that fractional catabolic rates and half-lives of leptin in circulation were similar at 48 h in nephrectomized and sham-operated rats, suggesting that production of leptin was unchanged after nephrectomy. Excretion of 125I derived from leptin in urine of nephrectomized rats was similar to that of sham-operated rats, and residual radioactivity was increased in the remaining kidneys excised from nephrectomized rats. These results demonstrate that 1) leptin concentrations are quickly restored to presurgical levels in nephrectomized rats, and 2) it is leptin elimination, not leptin production, that compensates to maintain leptin concentrations. Rapid metabolic adaptation of remaining renal tissue may explain the restoration of normal leptin elimination in nephrectomized rats.