Bubble dynamics in boiling histotripsy

Boiling histotripsy is a non-invasive, cavitation-based ultrasonic technique which uses a number of millisecond pulses to mechanically fractionate tissue. Though a number of studies have demonstrated the efficacy of boiling histotripsy for fractionation of solid tumours, treatment monitoring by cavitation measurement is not well studied because of the limited understanding of the dynamics of bubbles induced by boiling histotripsy. The main objectives of this work are to (a) extract qualitative and quantitative features of bubbles excited by shockwaves and (b) distinguish between the different types of cavitation activity for either a thermally or a mechanically induced lesion in the liver. A numerical bubble model based on the Gilmore equation accounting for heat and mass transfer (gas and water vapour) was developed to investigate the dynamics of a single bubble in tissue exposed to different High Intensity Focused Ultrasound fields as a function of temperature variation in the fluid. Furthermore, ex vivo liver experiments were performed with a passive cavitation detection system to obtain acoustic emissions. The numerical simulations showed that the asymmetry in a shockwave and water vapour transport are the key parameters which lead the bubble to undergo rectified growth at a boiling temperature of 100°C. The onset of rectified radial bubble motion manifested itself as (a) an increase in the radiated pressure and (b) the sudden appearance of higher order multiple harmonics in the corresponding spectrogram. Examining the frequency spectra produced by the thermal ablation and the boiling histotripsy exposures, it was observed that higher order multiple harmonics as well as higher levels of broadband emissions occurred during the boiling histotripsy insonation. These unique features in the emitted acoustic signals were consistent with the experimental measurements. These features can, therefore, be used to monitor (a) the different types of acoustic cavitation activity for either a thermal ablation or a mechanical fractionation process and (b) the onset of the formation of a boiling bubble at the focus in the course of HIFU exposure.     

Who Is Lost to Followup?: A Study of Patients with Distal Radius Fractures

Distal radius fractures are the most common upper extremity fracture, representing one-sixth of all fractures treated in emergency departments nationwide. Beyond the initial reduction and immobilization of these fractures, providing proper followup to ensure maintenance of the reduction and identify complications is necessary for optimal recovery of forearm and wrist functions. We sought to identify the clinical and demographic factors that characterize patients with distal radius fractures who do not return for followup and to assess the underlying causes for their poor followup rates. Compared with patients who were compliant with followup, those lost to followup had lower Physical and Mental Health scores on the SF-36 forms, more often were treated nonoperatively, and more likely had not surpassed secondary education. However, we found no difference between these two groups based on age, gender, mechanism of injury, marital status, or hand dominance. Early identification of patients who potentially are noncompliant can result in additional measures being taken to ensure the patient’s return to the treating hospital and physicians. This in turn will prevent complications attributable to lack of followup and allow more accurate assessment of results, thereby improving patient outcomes.     

Interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3)

The present study aimed to investigate the interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3). Five flavonoids (morin, silybin, naringin, naringenin and quercetin) were selected and their interaction characteristics with hOAT1 and hOAT3 were examined in MDCK cells overexpressing hOAT1 or hOAT3. Among tested flavonoids, morin and silybin exhibited significant inhibition effects on the cellular uptake of [3H]-para-aminohippuric acid ([3H]-PAH) in MDCK-hOAT1 cells with Ki of 0.46 microM and 24 microM, respectively, while all the tested flavonoids appeared to be less interactive with hOAT3 compared to hOAT1. A kinetic study suggested that morin and silybin inhibited hOAT1-mediated cellular uptake of [3H]-PAH in a competitive manner. Furthermore, morin and silybin were translocated by hOAT1 across the cellular membrane. In conclusion, the present study identified some of flavonoids as a new class of hOAT1 inhibitors, suggesting a potential for flavonoid-drug interactions via the modulation of hOAT1 activity.     

Surgical outcomes of 654 ulnar nerve lesions

OBJECT: In this article the authors present a retrospective analysis of 654 surgical outcomes in patients with ulnar nerve entrapments, injuries, and tumors during a 30-year period. METHODS: Data were gathered between 1968 and 1998 at Louisiana State University Health Sciences Center. Mechanisms of injuries or lesions included 460 entrapments at the elbow level (70%), 76 lacerations (12%), 52 stretches/contusions (8%), 34 fractures/dislocations (5%), 12 gunshot wounds (2%), two injection-induced injuries (0.3%), and 13 nerve sheath tumors (2%). In cases of entrapment, direct operative recordings uniformly demonstrated a slowing of conduction at the elbow, even in cases in which preoperative noninvasive studies had been nondiagnostic. Intraoperative electrical "inching" studies also demonstrated significant conduction abnormalities that lie just proximal to and through the olecranon notch rather than distal, beneath the flexor carpi ulnaris muscle. There were only eight exceptions to this. Lesions not in continuity due to the injury required primary or secondary end-to-end sutures or graft repair. Aided by intraoperative nerve action potential recording, lesions in continuity received either external or internal neurolysis and split repair or resection followed by end-to-end suture or graft repair. Functional recoveries of Grade 3 or better were seen in 81 (92%) of 88 patients who underwent neurolysis, 42 (72%) of 58 patients who received suture repair, and 24 (67%) of 36 patients who received graft repair. Nevertheless, fewer Grade 4 or 5 recoveries were reached than those seen in patients with radial or median nerve injuries. Nerve sheath tumors were resected with preservation of preoperative function in five of seven patients. CONCLUSIONS: Although difficult to obtain, useful functional recovery can be achieved with proper surgical management of ulnar nerve entrapments and injuries.     

Antiretroviral‐induced toxic epidermal necrolysis in a patient positive for human immunodeficiency virus

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are two variants on a spectrum of severe systemic hypersensitivity characterized by blistering maculopapular lesions and desquamation of the skin and mucus membranes. Although several causative agents, including infections, have been reported for SJS/TEN, medications remain the most common cause. We report the case of a 42‐year‐old man with human immunodeficiency virus (HIV) who developed TEN 4 months after starting treatment with darunavir and abacavir. The patient presented with upper body lesions, oral mucosal ulcerations, and impending airway compromise. He was intubated and admitted to the burns unit. Score for Toxic Epidermal Necrolysis (SCORTEN) was 5, with > 90% predicted mortality. However, after intravenous immunoglobulin and supportive treatment, the patient made a remarkable recovery. Abacavir and darunavir may be associated with SJS/TEN. TEN should be considered a risk for patients with HIV and should be monitored for cutaneous eruptions for several months after changes in treatment regimen.     

The Relationship of Plasma Glucose and HbA1c Levels among Emergency Department Patients with No Prior History of Diabetes Mellitus

Objectives: Patients without a history of diabetes mellitus may be incidentally found to be hyperglycemic in the emergency department (ED). If the hyperglycemia is due to undiagnosed diabetes, then an opportunity for detection exists. Hemoglobin A1c (HbA1c) provides a weighted average of blood glucose levels over the past several months; high HbA1c levels could indicate diabetes. The objective of this study was to determine whether hyperglycemia in ED patients without a history of diabetes was associated with higher HbA1c levels.
Methods: This was a prospective nonconsecutive case series of adults aged 18 years or older presenting to the ED with acute illness for whom a plasma glucose sample was drawn for clinical management. A history of diabetes/hyperglycemia or current symptoms of diabetes excluded patients. HbA1c levels were analyzed for a glucose cutoff of 110 mg/dL; the data were further analyzed using additional glucose cutoffs. Based on the Third National Health and Nutrition Examination Survey outpatient screening data, an HbA1c level ≥6.2% was considered elevated (sensitivity of 63% and specificity of 97% for identifying diabetes).
Results: There were 541 patients enrolled; the glucose level correlated with the HbA1c level ( r = 0.60, p < 0.001). Among the 331 patients with a glucose level ≥110 mg/dL, 22.4% had an elevated HbA1c level; among the 210 patients with a glucose level < 110 mg/dL, 7.6% had an elevated HbA1c level. There were few patients ( n = 13) with a glucose level ≥200 mg/dL, but most (85%) had an elevated HbA1c level. Among the 140 patients with a mildly elevated glucose level (110–125 mg/dL), 16.4% had an elevated HbA1c level.
Conclusions: Elevated HbA1c levels are found in ED patients with elevated random plasma glucose values. ED patients with hyperglycemia may warrant referral for diabetes testing.     

Evaluation of newly developed nose-only inhalation exposure chamber for nanoparticles

In this study, a direct-flow-type nose-only exposure chamber developed for inhalation toxicity experiments using a numerical analysis and experiments is evaluated. Maintaining a uniform flow rate and test article concentration are the critical factors when designing an inhalation exposure chamber. Therefore, this study evaluated whether the flow rate and particle size distribution at the injection nozzles at each port could be maintained with a deviation below 10%. To achieve this requirement, a nose-only exposure chamber flow field was simulated using a numerical analysis method, i.e. computational fluid dynamics (CFD) code FLUENT 6.3.26. Based on the simulation results, a test chamber was built and tested. The flow velocity was measured at the injection nozzle of the chamber and the aerosol particle size distribution was also measured at each port while inserting the test material into the exposure chamber. The results indicated that a uniform flow field distribution at each stage and port, the deviation of the flow velocity, and particle size distribution were all within 10%. Thus, the resulting nose-only exposure chamber could be described as well-designed.     

Prophylactic Pancreatic Stents: Does Size Matter? A Comparison of 4-Fr and 5-Fr Stents in Reference to Post-ERCP Pancreatitis and Migration Rate

Background and Aims  

The ideal pancreatic stent to prevent post-ERCP pancreatitis (PEP) has yet to be determined. The aim of our study was to assess the relative benefit of 4-Fr versus 5-Fr stents in a population at high risk for post-ERCP pancreatitis, and the relative frequency of spontaneous migration.     

Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1β in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.     

Ocular trauma resulting from paintball injury

Background  Paintball-related ocular injuries result in severe damage and loss of vision. Despite efforts to increase public awareness and improve safety features, the incidence of eye injuries has increased over time. We examined the characteristics and ocular effects of paintball injury at our tertiary referral center. Methods  Retrospective review of charts of patients with paintball injury between 1998–2005. Results  Fourteen patients were evaluated for paintball injury; 13 (93%) were male and one (7%) was female. Average age was 17 years (range from 9 to 30). Thirteen patients (95%) did not wear eye protection; one is unknown. Injuries occurred while playing paintball in three patients (21%); ten (71%) were injured in either accidental (four patients) or intentional (six patients) shootings not associated with play. Minimum follow-up was 6 weeks, except for one patient who was lost to follow-up. Seven patients (50%) had final visual acuity (VA) better than 20/200, six patients (43%) were 20/200 or worse, and information on one patient was not available. VA, except in one case, improved with treatment. Decreased VA in this case was due to proliferative vitreoretinopathy (PVR). Hyphema was noted in ten patients (71%), vitreous hemorrhage in eight (57%), retinal hemorrhage in six (43%), retinal tear or detachment in six (43%), commotio retinae in six (43%), iris injury in five (36%), keratopathy in four (29%), lens injury in two (14%), subluxation of lens in two (14%), secondary glaucoma in two (14%), open globe/intraocular foreign body (IOFB) in one (7%), choroidal rupture in one (7%), and proliferative vitreoretinopathy (PVR) in one (7%). Ten patients (71%) required intervention (surgery, laser retinopexy or cryotherapy). Conclusion  Paintball trauma results in significant ocular injury and loss of vision. Most injuries occur in unsupervised settings without proper eye protection. Ten patients (71%) were injured in accidental or intentional shootings. Lack of supervision and use of paintball materials as assault weapons make the risk for ocular injury more significant. Improved safety features of paintball equipment, along with continued education of proper eye protection, may reduce the incidence of severe ocular injuries. The authors have full control of the primary data, and will provide it to Graefe’s Archive for Clinical and Experimental Ophthalmology at their request. Neither author has any conflict of interest, financial or otherwise, to report. This work is supported by grants from Leir Foundation and Research to Prevent Blindness