Periprocedural management of patients receiving a vitamin K antagonist or a direct oral anticoagulant requiring an elective procedure or surgery.

The periprocedural management of patients receiving chronic therapy with oral anticoagulants (OACs), including vitamin K antagonists (VKAs) such as warfarin and direct OACs (DOACs), is a common clinical problem. The optimal perioperative management of patients receiving chronic OAC therapy is anchored on four key principles: (i) risk stratification of patient-related and procedure-related risks of thrombosis and bleeding; (ii) the clinical consequences of a thrombotic or bleeding event; (iii) discontinuation and reinitiation of OAC therapy on the basis of the pharmacokinetic properties of each agent; and (iv) whether aggressive management such as the use of periprocedural heparin bridging has advantages for the prevention of postoperative thromboembolism at the cost of a possible increase in bleeding risk. Recent data from randomized trials in patients receiving VKAs undergoing pacemaker/defibrillator implantation or using heparin bridging therapy for elective procedures or surgeries can now inform best practice. There are also emerging data on periprocedural outcomes in the DOAC trials for patients with non-valvular atrial fibrillation. This review summarizes the evidence for the periprocedural management of patients receiving chronic OAC therapy, focusing on recent randomized trials and large outcome studies, to address three key clinical scenarios: (i) can OAC therapy be safely continued for minor procedures or surgeries; (ii) if therapy with VKAs (especially warfarin) needs to be temporarily interrupted for an elective procedure/surgery, is heparin bridging necessary; and (iii) what is the optimal periprocedural management of the DOACs? In answering these questions, we aim to provide updated clinical guidance for the periprocedural management of patients receiving VKA or DOAC therapy, including the use of heparin bridging.

Decoherence of Near-Surface Nitrogen-Vacancy Centers Due to Electric Field Noise.

We show that electric field noise from surface charge fluctuations can be a significant source of spin decoherence for near-surface nitrogen-vacancy (NV) centers in diamond. This conclusion is based on the increase in spin coherence observed when the diamond surface is covered with high-dielectric-constant liquids, such as glycerol. Double-resonance experiments show that improved coherence occurs even though the coupling to nearby electron spins is unchanged when the liquid is applied. Multipulse spin-echo experiments reveal the effect of glycerol on the spectrum of NV frequency noise.

Proton magnetic resonance imaging using a nitrogen-vacancy spin sensor.

Magnetic resonance imaging, with its ability to provide three-dimensional, elementally selective imaging without radiation damage, has had a revolutionary impact in many fields, especially medicine and the neurosciences. Although challenging, its extension to the nanometre scale could provide a powerful new tool for the nanosciences, especially if it can provide a means for non-destructively visualizing the full three-dimensional morphology of complex nanostructures, including biomolecules. To achieve this potential, innovative new detection strategies are required to overcome the severe sensitivity limitations of conventional inductive detection techniques. One successful example is magnetic resonance force microscopy, which has demonstrated three-dimensional imaging of proton NMR with resolution on the order of 10 nm, but with the requirement of operating at cryogenic temperatures. Nitrogen-vacancy (NV) centres in diamond offer an alternative detection strategy for nanoscale magnetic resonance imaging that is operable at room temperature. Here, we demonstrate two-dimensional imaging of (1)H NMR from a polymer test sample using a single NV centre in diamond as the sensor. The NV centre detects the oscillating magnetic field from precessing protons as the sample is scanned past the NV centre. A spatial resolution of ∼12 nm is shown, limited primarily by the scan resolution.

Multipulse double-quantum magnetometry with near-surface nitrogen-vacancy centers.

We discuss multipulse magnetometry that exploits all three magnetic sublevels of the S=1 nitrogen-vacancy center in diamond to achieve enhanced magnetic field sensitivity. Based on dual frequency microwave pulsing, the scheme is twice as sensitive to ac magnetic fields as conventional two-level magnetometry. We derive the spin evolution operator for dual frequency microwave excitation and show its effectiveness for double-quantum state swaps. Using multipulse sequences of up to 128 pulses under optimized conditions, we show enhancement of the SNR by up to a factor of 2 in detecting NMR statistical signals, with a 4× enhancement theoretically possible.

Nanoscale nuclear magnetic resonance with a nitrogen-vacancy spin sensor.

Extension of nuclear magnetic resonance (NMR) to nanoscale samples has been a longstanding challenge because of the insensitivity of conventional detection methods. We demonstrated the use of an individual, near-surface nitrogen-vacancy (NV) center in diamond as a sensor to detect proton NMR in an organic sample located external to the diamond. Using a combination of electron spin echoes and proton spin manipulation, we showed that the NV center senses the nanotesla field fluctuations from the protons, enabling both time-domain and spectroscopic NMR measurements on the nanometer scale.

Limitations in Rechargeability of Li-O2 Batteries and Possible Origins.

Quantitative differential electrochemical mass spectrometry (DEMS) is used to measure the Coulombic efficiency of discharge and charge [(e(-)/O2)dis and (e(-)/O2)chg] and chemical rechargeability (characterized by the O2 recovery efficiency, OER/ORR) for Li-O2 electrochemistry in a variety of nonaqueous electrolytes. We find that none of the electrolytes studied are truly rechargeable, with OER/ORR <90% for all. Our findings emphasize that neither the overpotential for recharge nor capacity fade during cycling are adequate to assess rechargeability. Coulometry has to be coupled to quantitative measurements of the chemistry to measure the rechargeability truly. We show that rechargeability in the various electrolytes is limited both by chemical reaction of Li2O2 with the solvent and by electrochemical oxidation reactions during charging at potentials below the onset of electrolyte oxidation on an inert electrode. Possible mechanisms are suggested for electrolyte decomposition, which taken together, impose stringent conditions on the liquid electrolyte in Li-O2 batteries.

Continuous spinal analgesia after extensive lumbar spine surgery.

A 77-year-old male underwent L-1 to S-1 spine decompression and fusion from L-3 to S-1. A 25 G spinal catheter was placed intraoperatively and bupivacaine 1.25 mg/ml, fentanyl 2 microg/ml and morphine 3 microg/ml infused. The patient was pain-free for the duration of the infusion. Continuous spinal analgesia was effective after extensive spinal surgery. The risks of post-dural puncture headache, infection of wound and/or meninges and the optimum drug doses and combinations are yet to be quantified in this setting.

Nuclear double resonance between statistical spin polarizations.

We demonstrate nuclear double resonance for nanometer-scale volumes of spins where random fluctuations rather than Boltzmann polarization dominate. When the Hartmann-Hahn condition is met in a cross-polarization experiment, flip-flops occur between two species of spins and their fluctuations become coupled. We use magnetic resonance force microscopy to measure this effect between 1H and 13C spins in 13C-enriched stearic acid. The development of a cross-polarization technique for statistical ensembles adds an important tool for generating chemical contrast in nanometer-scale magnetic resonance.

Downstream from calcium signalling: mitochondria, vacuoles and pancreatic acinar cell damage.

Ca(2+) is one of the most ancient and ubiquitous second messengers. Highly polarized pancreatic acinar cells serve as an important cellular model for studies of Ca(2+) signalling and homeostasis. Downstream effects of Ca(2+) signalling have been and continue to be an important research avenue. The primary functions regulated by Ca(2+) in pancreatic acinar cells--exocytotic secretion and fluid secretion--have been defined and extensively characterized in the second part of the last century. The role of cytosolic Ca(2+) in cellular pathology and the related question of the interplay between Ca(2+) signalling and bioenergetics are important current research lines in our and other laboratories. Recent findings in these interwoven research areas are discussed in the current review.

Idiopathic scoliosis and pineal lesions in Australian children.

PURPOSE: To determine whether treatment of pineal lesions in children is associated with development of idiopathic scoliosis. METHODS: 38 boys and 10 girls with pineal lesions were identified. Their mean age at presentation was 10 years. The pineal pathology varied from cysts and epidermoid to teratoma, germinoma, pineocytoma, and glioblastoma. Treatment ranged from biopsy/extirpation to radiotherapy. RESULTS: 12 patients died. No scoliosis was found in any females or any of the deceased. Two boys had scoliosis: one had a 12-degree right upper thoracic curve with 32-degree kyphosis and the other had a 60-degree right thoracolumbar idiopathic curve, requiring a 2-stage arthrodesis. CONCLUSION: Pineal ablation is not related to the development of idiopathic scoliosis in humans.

The incidence of schizophrenia in European immigrants to Canada.

OBJECTIVE: The risk for schizophrenia in immigrants to Europe is approximately three times that of native-born populations. Discrimination and marginalization may influence the risk for schizophrenia within migrant populations. The primary objective of the present study was to determine whether the risk associated with migration was also evident 100 years ago. A second objective was to determine whether changing social stresses are associated with changes to the incidence of schizophrenia. METHOD: During the first two decades of the twentieth century, the Provincial Mental Hospital was the sole provider of psychiatric services in British Columbia, Canada. Detailed clinical records have been preserved for 99.5% of 2477 patients who had a psychiatric admission between 1902 and 1913. Diagnoses were made after a detailed file review and 807 patients met DSM-IV criteria for first-episode schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis not otherwise specified. Diagnoses had high inter-rater reliability. The incidence of schizophrenia in migrants from Britain or Continental Europe was compared with that in the Canadian-born population using indirect standardization and Poisson models. RESULTS: Migration from Britain or Continental Europe to Canada in the early twentieth century was associated with an increased rate of schizophrenia; IRR=1.54, (95% CI=1.33-1.78). Incidence increased over time in immigrants but not in the native-born population and this increase occurred during a period of economic recession. CONCLUSIONS: Migration was a risk factor for schizophrenia a century ago as it is today. This risk occurred in white migrants from Europe and increased during a period of increased social stress.

Movement of calcium signals and calcium-binding proteins: firewalls, traps and tunnels.

In the board game 'Snakes and Ladders', placed on the image of a pancreatic acinar cell, calcium ions have to move from release sites in the secretory region to the nucleus. There is another important contraflow - from calcium entry channels in the basal part of the cell to ER (endoplasmic reticulum) terminals in the secretory granule region. Both transport routes are perilous as the messenger can disappear in any place on the game board. It can be grabbed by calcium ATPases of the ER (masquerading as a snake but functioning like a ladder) and tunnelled through its low buffering environment, it can be lured into the whirlpools of mitochondria uniporters and forced to regulate the tricarboxylic acid cycle, and it can be permanently placed inside the matrix of secretory granules and released only outside the cell. The organelles could trade calcium (e.g. from the ER to mitochondria and vice versa) almost depriving this ion the light of the cytosol and noble company of cytosolic calcium buffers. Altogether it is a rich and colourful story.

A new model of glaucoma filtering surgery in the rat.

PURPOSE: The most common reason for long-term failure of glaucoma filtering surgery (GFS) is scarring of the external filtering "bleb" tissues. The identification of the factors that mediate this process, as well as the development and initial testing of new therapies to limit scarring is enhanced by the use of appropriate animal models. The standard animal model for studying GFS is the rabbit but newer investigative tools that examine changes induced in biologic systems at a genetic level have made development of a rat model desirable. METHODS: Glaucoma filtering surgery was performed on 20 Sprague-Dawley rats by introducing a 30-gauge silicone cannula through a penetrating scleral tunnel, under a limbal-based conjunctival flap and suturing the conjunctiva closed. Identical GFS was performed on 3 additional rats, which underwent histologic evaluation at days 2, 5, and 11, following surgery.Fistulizing surgery was also performed on 6 Sprague-Dawley rats, for comparison, by creating a full-thickness needle sclerostomy under a limbal-based conjunctival flap and suturing the conjunctiva closed. RESULTS: Following the cannula GFS, well-elevated filtering blebs formed and these gradually failed over the course of 8 to 13 days. Needle tract sclerostomy filtering blebs formed at the site of the fistulizing surgery but rapidly failed over the course of 2 to 3 days. CONCLUSION: Cannulated filtering surgery in the rat provides a longer lasting and more predictable model than needle tract sclerostomy for studying wound healing following GFS and may facilitate the study of induced changes at the gene level.

Time-specific intraocular pressure curves in Rhesus macaques (Macaca mulatta) with laser-induced ocular hypertension.

OBJECTIVE: To detect and categorize time-specific variations in daytime intraocular pressure (IOP) found in Rhesus monkeys with laser-induced ocular hypertension. PROCEDURES: Ten male monkeys with argon laser-induced ocular hypertension in one eye were anesthetized with ketamine hydrochloride, and the IOP measured in both eyes at 7 a.m., 7.30 a.m., and then hourly until 1 p.m. with a Tonopen trade mark XL applanation tonometer. Intraocular pressure time profiles for both eyes in each animal were developed. The means +/- SD of the IOPs for both eyes were calculated for the whole 6-h study period, and the values compared statistically. The difference between the lasered eye mean IOP standard deviation and the normal eye mean IOP standard deviation for each animal during the 6-h follow-up was also calculated and compared. RESULTS: Mean IOP (+/- SD) in the glaucoma and normal eyes for the 10 animals during the 6-h study was 32.6 +/- 2.5 and 14.9 +/- 2.5 mmHg, respectively. The IOP was significantly higher in the experimental eye than in the normal eye (P = 0.0008). The mean IOP in the lasered eye did not significantly change during the study period, whereas a slight but significant increase in IOP of the normal eye over the study period was recorded (P = 0.003). The variance in IOP in the hypertensive eyes was considerably greater than that in the untreated control eyes. From 7 a.m. to 1 p.m. the IOP declined in five eyes and increased in the other five eyes with laser-induced ocular hypertension. CONCLUSIONS: The time-specific IOP variation pattern in the daytime in the laser treated eyes is significantly greater than the variation in the normotensive eyes. This shows that in order to detect statistical differences between IOP variations induced by an IOP-reducing drug, and the exaggerated spontaneous IOP variations present in the laser-induced hypertensive eye, sufficient animals should be included in any study. Understanding the time-specific IOP variation present in a group of monkeys with laser-induced ocular hypertension is essential prior to using the model for the evaluation of IOP-reducing drugs.

Corneal thickness and endothelial cell density measured by non-contact specular microscopy and pachymetry in Rhesus macaques (Macaca mulatta) with laser-induced ocular hypertension.

PURPOSE: Sustained increase in intraocular pressure (IOP) in humans results in a loss of corneal endothelial cells and an increase of corneal thickness. The effects of chronically elevated IOP on the corneal endothelium of monkeys with laser-induced ocular hypertension, a commonly used animal model of human glaucoma have not been documented. This study examined the central corneal thickness (CCT), the corneal endothelial cell density (ECD), and the corneal endothelial cell size (ACS) in Rhesus monkeys with experimental ocular hypertension. Materials and methods. Ten male monkeys with argon laser-induced ocular hypertension in one eye for an average duration of 2.4+/-0.7 years, were sedated with ketamine hydrochloride, and the CCT, ECD, and ACS measured at the center of the cornea of both eyes with a Topcon SP-2000P non-contact specular microscope (Topcon America Corporation((R)), Paramus, NJ, USA). CCT was also measured using a DHG-500 Pachette ultrasonic pachymeter (DHG Technology Inc., Exton, PA, USA). Mean and standard deviation (S.D.) of CCT, ECD and ACS for each eye was calculated and statistically compared.Results. Mean CCT in the hypertensive and normal eyes measured by specular microscopy was 0.477+/-0.023mm and 0.468+/-0.020 mm, respectively. Mean ECD in the hypertensive and normal eyes was 2601.7+/-631.8 and 3990.2+/-402.9 cells mm(-2), respectively. The mean size of the endothelial cells was 252.4+/-23.9 micro m(2) in the normal eye and 408.7+/-115.0 microm m(2) in the hypertensive eye. No significant difference in the measurement of CCT was observed between the specular microscope and the pachymeter (p=0.46). No significant difference in the mean CCT was observed between the two eyes (p=0.4820), whereas the mean ECD was significantly lower in the hypertensive eye than in the normal eye (p<0.001). The ECD was inversely related to the length of IOP elevation (p<0.001). CONCLUSIONS: No difference in the corneal thickness measurement was observed between the specular microscopy and the pachymetry techniques. Chronic ocular hypertension did not significantly affect the CCT, but caused a significant loss of endothelial cells in the center of the cornea of the laser treated eyes compared to the normotensive eyes. The duration of elevated IOP was the most important factor affecting the ECD.

Introduction of endovascular aneurysm repair into community practice: initial results with a new Food and Drug Administration-approved device.

PURPOSE: The purpose of this study was to determine the outcome of endovascular aneurysm repair in a defined geographic region during the first 2 years after Food and Drug Administration approval of a new endovascular device. METHOD: Clinical results of all attempted endovascular aneurysm repairs from 1999 to 2001 with the AneuRx stent graft in the northern California/Nevada region were reviewed. All cases performed in 23 hospitals by 21 endovascular treatment teams were included on an intent-to-treat basis. Community physician training, proctoring, and assistance in case selection was provided by the manufacturer, with outcome monitored by external physician observers and clinical vascular specialists. Results in 22 community hospitals were compared with concurrent results in the regional university hospital training center and with results from the controlled, multicenter AneuRx clinical trial. RESULTS: Endovascular aneurysm repair was attempted in 257 patients by 20 endovascular teams working in 22 community hospitals. The mean number of cases per team was 13 +/- 2 (range, 1 to 36). Patient age was 74.1 +/- 6.5 years (89% men and 11% women), and 29% of patients were not candidates for open surgical repair because of multiple medical comorbidities. Mean aneurysm diameter was 5.7 +/- 0.8 cm. The endoluminal stent graft was successfully deployed in 254 patients (98.8%). In two patients, iliac access could not be obtained, and in one case, the iliac limb was misdeployed and the patient underwent successful open surgical repair. The surgical conversion rate was two of 257 patients (0.8%). The 30-day mortality rate was 1.2%, with one patient dying of stroke, one of multisystem organ failure, and one of cerebral hemorrhage. No device-related deaths occurred. Secondary procedures were performed in 8% of patients. Primary graft patency rate was 98%, and secondary graft patency rate was 100%. Concurrent university training center experience with 100 patients with similar characteristics and aneurysm size was not statistically different (deployment success rate, 100%; 30-day mortality rate, 0%; surgical conversion rate, 0%; secondary procedure rate, 8%). No aneurysm ruptures and no late surgical conversions have been seen in either the community or university experience, with follow-up periods extending to 2 years. CONCLUSION: Early results of endovascular aneurysm repair introduced into community practice are favorable. Initial community experience, with clinical support from the manufacturer, does not appear to differ significantly from concurrent results in the university training center or from results reported from the multicenter controlled clinical trial with the same device.

Three-dimensional echocardiography in congenital heart disease: a continuum of unfulfilled promises? No. A presently clinically applicable technology with an important future? Yes.

Three-dimensional echocardiography has important clinical applications to congenital heart disease. Such applications include assessment of ventricular volumes, and unique imaging planes and projections of septae and atrio-ventricular and semi-lunar valves. Advances in ultrasound and computer technology will improve the process of three-dimensional echocardiography to continue to bring it to everyday clinical utility application.

Three-dimensional echocardiography of the atrial septum.

This article details the important contribution of three-dimensional echocardiography for catheterization device closure of secundum atrial septal defects. Aspects presented include three-dimensional echocardiographic application in preselection of patients and in selection of the type and size of the atrial septal occluder devices. Unique three-dimensional echocardiographic imaging planes are shown that depict the size and shape of the defect, the important rim tissue surrounding the defect, and the images that demonstrate successful device placement. Details of the acquisition phase, digital reformatting, and the eventual rendering of standard three-dimensional echocardiographic imaging planes of the atrial septum are shown. Three-dimensional echocardiography not only provides important additional information, but also enhances understanding of standard two-dimensional studies.

Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.

The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p