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Summary Liquid mixing is an important component of many microfluidic concepts and devices, and computational fluid dynamics (CFD) is playing a key role in their development and optimization. Because liquid mass diffusivities can be quite small, CFD simulation of liquid micromixing can over predict the degree of mixing unless numerical (or false) diffusion is properly controlled. Unfortunately, the false diffusion behavior of higher-order finite volume schemes, which are often used for such simulations, is not well understood, especially on unstructured meshes. To examine and quantify the amount of false diffusion associated with the often recommended and versatile second-order upwind method, a series of numerical simulations was conducted using a standardized two-dimensional test problem on both structured and unstructured meshes. This enabled quantification of an ‘effective’ false diffusion coefficient (Dfalse) for the method as a function of mesh spacing. Based on the results of these simulations, expressions were developed for estimating the spacing required to reduce Dfalse to some desired (low) level. These expressions, together with additional insights from the standardized test problem and findings from other researchers, were then incorporated into a procedure for managing false diffusion when simulating steady, liquid micromixing. To demonstrate its utility, the procedure was applied to simulate flow and mixing within a representative micromixer geometry using both unstructured (triangular) and structured meshes. Copyright © 2016 John Wiley & Sons, Ltd.

Aluminum beer bottles recently have been introduced as an alternative to traditional glass bottles or aluminum cans. Advertisements claim that the new aluminum bottles keep beer “colder longer” than glass bottles. Because the thermal conductivity of aluminum is over 150 times that of typical soda-lime glass, and because the bottle wall is thinner, this claim appears counterintuitive. In this investigation, the thermal performance of commercially available aluminum and glass beer bottles was examined using experimental, analytical, and computational methods. It was found that when exposed to ambient air, glass and aluminum bottles perform in a nearly identical manner with respect to keeping their contents cold. Each bottle showed an approximately 15°C temperature rise over a 2.7-hour period. Heat transfer is controlled by natural convection and thermal radiation at the outer bottle surface; hence, the difference in thermal conductivity between the bottles has no significant impact on the temperature transi...

The incorporation of engineering design projects into core undergraduate engineering courses can be a powerful method to facilitate student learning. This paper describes a project centred around the design of a solar storage wall (SSW)—an asymmetric structure that is used to capture solar energy for building heating. The project, which combines computer-based engineering modelling and economic analysis, is assigned to undergraduate students in a three-semester-hour introductory heat and mass transfer course at the University of Tennessee at Chattanooga.

When performing quantitative (or probabilistic) risk assessments, it is often the case that data for many of the potential events in question are sparse or nonexistent. Some of these events may be well-represented by the binomial probability distribution. In this paper, a model for predicting the binomial failure probability, P, from data that include no failures is examined. A review of the literature indicates that the use of this model is currently limited to risk analysis of energetic initiation in the explosives testing field. The basis for the model is discussed, and the behavior of the model relative to other models developed for the same purpose is investigated. It is found that the qualitative behavior of the model is very similar to that of the other models, and for larger values of n (the number of trials), the predicted P values varied by a factor of about eight among the five models examined. Analysis revealed that the estimator is nearly identical to the median of a Bayesian posterior distribution, derived using a uniform prior. An explanation of the application of the estimator in explosives testing is provided, and comments are offered regarding the use of the estimator versus other possible techniques.

The complex variable boundary element method (CVBEM) for simply connected domains is extended to include the use of quadratic elements and interpolating functions. The derivation follows the format for linear elements given in the literature, with second-degree Lagrange polynomials taken as the interpolating functions. The quadratic-element CVBEM nodal- and interior-point equations are given in detail, and the resulting formulation is successfully tested by solving example problems with available analytical solutions. Comparisons of computational efficiency and accuracy are made between the solutions obtained using linear and quadratic elements. Additional comparisons are made using published results from other boundary element methods.

In continuous-flow enzymatic microbioreactors, enzymes on the channel walls catalyze reaction(s) among feed chemicals, resulting in the production of some desirable material or the destruction of some undesirable material. Computational models of microbioreactors were developed using the CFD-ACE+ multiphysics simulation package. These models were validated via comparison with experimental data for the destruction of urea, catalyzed by urease. Similar models were then used to assess the impact of internal features on destruction efficiency. It was found that triangular features within the channels enhanced the destruction efficiency more than could be attributed to the increase in surface area alone.

The study was undertaken to determine the influence of various doses of aspi rin (ASA) therapy on platelet adherence to injured endothelium. Twenty-four mongrel dogs were assigned to one of four treatment groups in a randomized, blinded fashion. Each group received ASA in one of three doses: 1 mg/kg, 5 mg/kg, or 10 mg/kg or no ASA therapy (control group). After five days of ASA therapy, the dogs underwent unilateral carotid endarterectomy (CEA), in a ran domized fashion, with the contralateral carotid artery serving as control within each dog. Indium 111 oxine-labeled autologous platelets were injected into the dogs twenty minutes before the reestablishment of flow through the endarterec tomized carotid artery. Platelet scintigraphy was performed at hours 3, 24, 48 and 72 postoperatively. ASA therapy was continued postoperatively for seventy- two hours. Data were analyzed by comparing the mean platelet uptake ratios (operative to nonoperative sites) between groups. When all ASA groups were combined and compared with control values, ASA therapy significantly decreased (p < 0.05) platelet adherence up to seventy-two hours postoperatively. The same effect was observed with low- (1 mg/kg) and medium- (5 mg/kg) dose ASA, which significantly reduced (p < 0.05) platelet adherence to the endarterectomized site at hours 3, 24, 48, and 72. In contrast, there was no significant reduction in platelet uptake in the high-dose (10 mg/kg) ASA group. These results indi cate that ASA therapy given in a dosage of 1 or 5 mg/kg for at least five days preoperatively is beneficial in decreasing platelet adherence after CEA in dogs. Conversely, at a dose of 10 mg/kg, platelet uptake is not consistently inhibited. This study supports previous findings that lower doses of ASA (1-5 mg/kg) are superior to high-dose ASA (10 mg/kg) in inhibiting platelet adherence to injured endothelium in vivo.

An efficient computer program called GRID2D/3D has been developed to generate single and composite grid systems within geometrically complex two- and three-dimensional (2D and 3D) spatial domains that can deform with time. GRID2D/3D generates single grid systems by using algebraic grid generation methods based on transfinite interpolation. The distribution of grid points within the spatial domain is controlled by stretching functions and grid lines can intersect boundaries of the spatial domain orthogonally. GRID2D/3D generates composite grid systems by patching together two or more single grid systems. The patching can be discontinuous or continuous. For 2D spatial domains the boundary curves are constructed by using either cubic or tension spline interpolation. For 3D spatial domains the boundary surfaces are constructed by using a new technique, developed in this study, referred to as 3D bidirectional Hermite interpolation.

The purpose of this animal study was to investigate the histopathologic consequences of esophageal exposure to a variety of medications known to be injurious to the human esophagus. Twenty-four New Zealand white rabbits were utilized. Tablets or control plastic beads were secured to a silk suture thread and positioned in the rabbit esophagus through a proximal esophagostomy and a gastrostomy. Test medications were allowed to dissolve passively on the surface of the esophageal mucosa in the anesthetized rabbits. After 1 hr of drug exposure, the rabbits were killed and the esophagus removed and examined. No gross abnormalities were detected with the exception of a mild degree of erythema at some of the exposure sites. All medications and control beads produced microscopic mucosal changes when compared to suture controls. The beads and test medications caused thinning of the epithelium and increased subepithelial edema (P less than 0.05). Two changes, however, were unique to animals exposed to test medications: fraying and/or splitting of the epithelium and the presence of balloon cells (P less than 0.05). Balloon cells represent damaged squamous epithelial cells recognizable by their distended, globoid shape. The prevalence of balloon cells ranged from 22% to 89% of sites exposed to drug and was most commonly associated with potassium. Of all drugs reported to cause injury to the human esophagus, potassium chloride has been reported to produce the most severe lesions, including esophageal stricture and perforation.(ABSTRACT TRUNCATED AT 250 WORDS)

Conditions required for in vitro bonding of14C-ofloxacin (OFX) to polytetrafluoroethylene suture (PTFE) were investigated. Bonding of OFX to PTFE was enhanced 22- and 75-fold in the presence of the cationic surfactant benzalkonium chloride (BAC) or silver and organic solvents (S/O), respectively. The optimal temperature and time of incubation for maximum OFX bonding was 37°C for 1 h (BAC) and 37°C for 25 min (S/O). BAC- and S/O-treated PTFE bound 3.94 nmoles and 17.79 nmoles OFX/cm suture. Prolonged in vitro incubation of OFX/PTFE for 7 days at 37°C in the presence of serum or saline resulted in 50% OFX retention. In vivo studies on OFX/PTFE placed into canine carotid arteries showed 8% OFX retention. The intravenous infusion of coagulase-positiveStaphylococcus aureus into OFX/PTFE animals resulted in colonization. Although significant in vitro bonding of OFX to PTFE was observed, in vivo studies demonstrate an accelerated release and inferior OFX/PTFE activity against microbial colonization.

The results of a numerical study of the fundamental interactions of engineering design and micromixing on conversion in packed microchannels are presented. Previously, channel-based microreactors made of molded silicon plastic were designed, fabricated, and experimentally tested. These reactors have enzymes immobilized on the channel walls by various methods including layerby-layer nano self-assembly techniques. They also contain molded packing features to add reactive surface area and to redistribute the fluid. An arbitrary but intuitively sensible packing arrangement was initially chosen and used in experimental studies. The current computer simulation study was undertaken to understand how static laminar mixing affects the conversion efficiency. The reactors previously used experimentally have been simulated using CFD-ACE+ multiphysics software (ESI CFD Inc., Huntsville, AL). It is found that packing significantly increases conversion when compared with empty channels over the entire flow rate range of the study (0.25

Many industrial chemical processes involve the mixing of two or more liquids. By reducing chemical reactors to microscale dimensions, engineers seek to take advantage of decreased diffusion lengths, leading to increased effectiveness (e.g., higher purity of product) over larger process components. In this study, computational models developed using the commercial multiphysics code CFD-ACE+ are used to predict flow within microreactor channels. Two aqueous streams enter a channel—one containing a contaminant and the other devoid of the contaminant. Changes in two geometric attributes are investigated with respect to their effect on mixing of the streams: 1) packing feature layout within the channel and 2) channel aspect ratio. Reynolds numbers (Re) for the simulations range between 0.1 and 100. Results indicate that both packing feature position within the channel and channel aspect ratio can have a substantial impact on mixing. Between Re = 0.1 and Re = 1, mixing efficiency generally decreases with increasing Re; however, as the Re is increased from 1 to 100, fluid flow patterns in the channel are altered, and wake regions and streamline changes created by the packing features lead to improved mixing. Examples showing enhanced chemical conversion during heterogeneous catalysis as a result of better mixing are also presented.Copyright © 2007 by ASME

Post-endarterectomy platelet deposition may play an important role not only in vessel wall healing, but also in the development of progressive stenosis. Using a canine model, we investigated the effect of endothelial cell seeding on platelet deposition on endarterectomised arteries. Thirteen dogs underwent bilateral carotid intimectomy (5 cm long) and one side was seeded with an average of 2 × 10 6 viable freshly harvested endothelial cells. Blood flow was restored 20 min after seeding. On the contralateral side, a sham-seeding was performed. Deposition of 111 indium-labelled autologous platelets was studied with sequential gamma camera images 3–5h, 1, 2, 3, 4 days and 4 weeks after surgery. Platelet uptake was statistically reduced on the seeded side. Animals were killed at 4 weeks (nine dogs) and 5 weeks (four dogs) after surgery. Seven arteries for each group were found to be occluded. We conclude that endothelial cell seeding on endarterectomised arteries is feasible and reduces platelet uptake. Improvement in the efficiency of seeding and reduction of endothelial cell loss might permit clinical application of this technique.

The treatment of corners in the complex variable boundary element method for simply-connected domains is considered. A methodology is developed for all possible combinations of Dirichlet, Neumann, and Robin boundary conditions at the corner. It is shown that no special augmentation of the resulting matrix equations is necessary when one follows the guidelines set forth in this paper. The methodology is successfully applied to four example problems with available analytical solutions, and comparisons are also made with published results from a specialized real variable boundary element method corner-handling formulation.

The in vitro dissolution time and pH were measured for 16 drug products in capsule or tablet form representative of oral medications known to cause esophageal injury. The test drugs included Vibramycin, Minocin, quinidine sulfate, Cleocin HCl, Indocin, Tolectin 200, ferrous sulfate, vitamin C, aspirin, Procardia, phenobarbital, Dilantin, Butazolidin, Noctec, K-Dur, and Quinaglute. Artificial saliva (10 mL) was placed in a small beaker along with a pH probe connected to a digital display pH meter and a strip—chart recorder. The salivary pH was measured at baseline and continuously during the dissolution of each test medication and the time taken for complete dissolution was recorded. This experiment was repeated six times for each drug. Baseline and final dissolution pH were compared statistically for differences using the Wilcoxon matched-pairs signed-ranks test. Significance was established at the 0.05 level. Only three medications tested (vitamin C, aspirin, and Dilantin) produced a dissolution pH outside the range of physiological esophageal pH values. Although the majority of the test drugs significantly altered the baseline pH, the final dissolution pH did not fall outside the physiologic range. Nine of the 16 test drugs dissolved completely within 10 minutes, whereas the remaining 7 drugs took 30 minutes or longer (up to 24 hours) to dissolve. We conclude that the dissolution pH of potentially caustic medications does not appear to be a primary mechanism of drug-induced esophageal injury, whereas a rapid dissolution rate may play an important role in the pathogenesis of the lesion.

Although the hemodynamic characteristics and durability of the St. Jude valve prosthesis have been reported, the need for and the degree of anticoagulation in patients who receive these valves remain uncertain. Our 10-year experience with 165 patients (100 men and 65 women, mean age of 58 ± 13 years), who underwent valve replacement with St. Jude prostheses, is reported. Of the 165 patients, 147 were treated with warfarin. A prothrombin time 1.3 to 1.8 times control (range 15 to 20 seconds) was maintained in 134 patients with single valve and 1.8 to 2 times control (range 20 to 25 seconds) in 13 patients with double valve prostheses. The 10-year actuarial event-free incidence from thromboembolic and hemorrhagic complications was 84 and 95%, respectively. Of the 8 patients receiving antiplatelet therapy alone, 4 had thromboembolic events. Of the 10 patients on neither warfarin nor antiplatelet therapy, 3 had thromboembolic events. The 10-year actuarial event-free incidence from valve failure was 95%. The 10-year actuarial patient survival was 55%. Thus, the St. Jude valve is a safe and reliable prosthesis with acceptable overall long-term performance in patients given a modest anticoagulation regimen. Patients who receive St. Jude prosthetic valves without anticoagulants have a high incidence of thromboembolic events despite therapy with antiplatelet agents.

A unique centralized approach to clinical research in a University Medical Center is described. This approach utilizes Pharm. D. practitioners as the on site administrators of ongoing studies at each medical specialty department. A Central Research Administrative Group provides overall administration of the program and liaises with pharmaceutical companies, representing the University.This approach has created a new role model for Pharm. D. practitioners as administrators of clinical research. Using a two-tiered organization, our centrally organized approach has achieved all of our short and medium range objectives within a three year period.This approach may serve as a model for organizing clinical research throughout United States Medical Centers.

Heparin-associated thrombocytopenia has been reported most commonly with bovine lung preparations. We prospectively evaluated the incidence of thrombocytopenia in 43 patients receiving intravenous continuous infusions of either bovine lung heparin, manufactured by a new process, or a standard porcine intestinal mucosa heparin for a minimum of five days in a double-blind, randomized fashion. The decision to continue heparin therapy beyond five days was made by the patient's primary physician. All patients had documented acute thromboembolic disease, pretherapy platelet counts > 150000/mm3, and no evidence of prior coagulation disturbance. No patients had undergone cardiopulmonary bypass or hemodialysis within seven days previous to the initiation of heparin therapy. Thrombocytopenia was defined as a decline in platelet count from the normal range of 150000–350000/mm3 to 3. Thrombocytopenia occurred in one patient (4.6 percent) receiving bovine lung heparin on day nine of therapy and in no patients (0 percent) receiving porcine intestinal mucosa heparin. Adverse reactions occurred in nine patients (42.9 percent) receiving porcine intestinal heparin and five patients (22.7 percent) receiving bovine lung heparin. This difference was not statistically significant. The results of this study indicate that the incidence of thrombocytopenia is low (< five percent) with both bovine lung heparin, manufactured by a new process, and porcine intestinal mucosa heparin when therapy is limited to short therapeutic courses (< 1 week).

We are reporting a case of theophylline toxicity after the initiation of i.v. aminophylline and isoproterenol in the treatment of cerebral vasospasm. The dose of aminophylline (125 mg/hour) previously recommended results in a toxic serum theophylline concentration in a majority of patients if the infusion is continued for more than 24 to 48 hours. The rapid achievement of an optimal serum level is obtained with a standard loading dose of 8.0 mg/kg. The initial infusion rate should be based on calculated pharmacokinetic data. Maintenance dosing adjustments are then based on serum determinations and the presence of toxic effects.

Misoprostol, a methylester analog of prostaglandin E1, with antisecretory and cytoprotective properties, has undergone extensive investigation and has received Food and Drug Administration approval for the prevention of nonsteroidal-induced ulceration. The drug represents the first synthetic, orally active prostaglandin evaluated for the treatment of peptic ulcer disease. Clinical studies reveal a trend toward slightly lower healing rates with misoprostol when compared with histamine (H2)-receptor antagonists in the treatment of gastric and duodenal ulcers. In addition, misoprostol was less effective than H2-blockers in reducing ulcer pain, and caused a higher incidence of adverse reactions, particularly diarrhea occurring in up to 13 percent of the patients treated. Several studies have shown misoprostol to be superior to cimetidine and sucralfate in the prevention of alcohol- and drug-induced gastritis. This report summarizes the biopharmaceutics, pharmacokinetics, and clinical efficacy of misoprostol in the treatment of gastric and duodenal ulcers and in the prevention of mucosal injury.

A retrospective study of 55 patients with a benign esophageal stricture showed that in 11 patients (20%) the cause was a drug-induced lesion due to potassium chloride (3), tetracyclines (3), aspirin (2), vitamin C (1), phenytoin (1), and quinidine (1). Five of the 11 patients would have been diagnosed as having a reflux etiology of their stricture if 24-hour esophageal pH monitoring was not performed. Six patients responded to dilatation and five patients required resection or bypass. A prospective study of 18 asymptomatic volunteers showed a high incidence of esophageal lodgment of a radiolabeled medicinal capsule, with subsequent dissolution and release of the isotope. This occurred most frequently in elderly subjects and was reduced by increasing the volume of water chaser. The sites of lodgment correspond to the location of the observed strictures in the patient population. An in vitro study showed that, when the causative drugs were mixed with saliva, dissolution occurred within 60 minutes and was associated with significant changes in pH. These investigations show that drug-induced esophageal strictures are more common than previously appreciated, and can be confused with a reflux etiology. Diagnosis is suggested by a history of drug ingestion, location of the stricture, and a normal esophageal acid exposure on 24-hour pH monitoring. The severity of the esophageal injury is variable and requires dilatation to resection for therapy.

Five consecutively admitted major burn patients were successfully supported with a high calorie, high protein diet supplemented with a blenderized diet (formula) that was prepared in our hospital. The egg, rice, and milk base formula provided over 60 percent of the average daily caloric requirements essential to their recovery. It was effective in preventing significant weight loss and promoting wound healing and successful skin grafting. The formula is inexpensive, palatable, of high quality protein, and provides a complete feeding when administered daily in conjunction with vitamin and mineral supplements.

An iterative variation of the linear-element complex variable boundary element method (CVBEM) is used to generate grid points in two-dimensional simply connected spatial domains. As in many grid generation techniques, the solution of Laplace's equation is involved; however, the boundary element formulation results in a much smaller set of simultaneous equations, and once the values of the complex potential at the boundaries are fully determined, the internal grid point distribution can be altered without resolving the elliptic system. The boundary conditions implemented produce grid line orthogonality at the domain boundaries. Additionally, by using complex variables in the formulation, numerical integration is avoided. The utility of the method is demonstrated by (1) generating grid systems for several irregular geometries and (2) obtaining a numerical solution for the flow field associated with one of the geometries.

This is the first case report of esophageal injury caused by Percogesic. A 31-year-old healthy white woman presented with dysphagia and retrosternal pain following the ingestion of a Percogesic tablet. The patient felt the tablet lodge in her mid-esophagus even though she ingested it with a cupful of water and in the upright position. Additional fluid was taken to dislodge the tablet with no success. Past medical history was unremarkable for heartburn, regurgitation, or dysphagia. Upper gastrointestinal endoscopy revealed a well-circumscribed deep ulceration in the mid-esophagus. Hospitalization was required due to persistent dysphagia. Treatment consisted of a three-day regimen of liquid antacid, intravenous ranitidine hydrochloride, and metoclopramide. This case emphasizes that pill entrapment can occur in the esophagus in healthy individuals, even when taken in the upright position with plenty of fluid; and mucosal injury can be produced by drugs not generally reported to cause gastrointestinal adverse effects or mucosal injury.

A new device has been developed that is capable of processing information from a standard Doppler signal on the relative section (RS) of arteries during the cardiac cycle. RS is a new parameter proportional to the vessel cross-section and its changes during the cardiac cycle. This parameter does not give any morphologic information on the vessel itself, but it can help in completing Dop pler analysis, providing information on vessel elasticity. RS radius (R) and ve locity (V) (traditional Doppler) signals were routinely recorded under constant-pressure conditions. The device was tested in vivo by recording the R and V tracings on 20 common femoral arteries (cf) in dogs. These measure ments were compared with the R and V tracings obtained from the largest femoral branch (fb). R and V tracings were also obtained on 20 femoral arteries after surgically induced stenosis (above, at, and below the stenosis). Both exper iments showed a significant depression of the R tracings (p < 0.01). No signifi cant difference was found between the radius value and three-projection angiography of the stenosis (p=ns). The ability of the device to determine the elasticity of the arterial wall was evaluated in vitro on 10 specimens of athero sclerotic human tibial arteries, obtained from amputated lower extremities, and on 10 samples of dog femoral arteries, and the evaluations were compared. A significant difference in the radius root mean square values was found between the 2 groups (p < 0.01). The authors conclude that this device is capable of determining a new parameter (RS) that is proportional to the cross-section of the examined artery. They have also demonstrated that RS provides useful in formation about arterial wall elasticity.

Schatzki's ring is a distinct anatomical entity associated with hiatal hernia; however, its significance is unclear. Thirty-two patients with a radiologically demonstrated Schatzki's ring were compared with 32 patients with hiatal hernia and no Schatzki's ring. Schatzki's ring was confirmed on endoscopy in 59 percent of patients. Seventy-five percent of patients with Schatzki's ring presented with dysphagia compared with 41 percent of control patients (p less than 0.01). Heartburn and regurgitation were less frequent than in control subjects (38 percent versus 91 percent, p less than 0.0001). Schatzki's ring patients were found to have a lower incidence of proven gastroesophageal reflux on 24-hour pH monitoring. Those with proven reflux were found to have a more efficient lower esophageal sphincter than control patients. Sixty-two percent of Schatzki's ring patients without proven reflux had a history of chronic ingestion of drugs known to be damaging to the esophageal mucosa, whereas only 26 percent of patients with reflux had this history. This was found in 16 percent of controls. Sixty-two percent of Schatzki's ring patients without reflux responded to a single dilatation compared with 37 percent of those with reflux. These findings suggest an etiologic relationship between pill lodgement and Schatzki's ring in patients without reflux and indicate that different therapy should be employed in these patients.

The tendency of a gelatin capsule to lodge in the esophagus, dissolve, and release its contents, as a potential etiology of drug-induced esophageal injury, was studied in 18 asymptomatic volunteers. Their ages ranged from 21 to 81 years, with nine subjects over 70 years old. Esophageal transit time of liquids was measured in all subjects after which the esophageal transit time of a #00 gelatin capsule containing technetium (99mTc) sulfur colloid was measured with a 120 ml and a 15 ml water bolus. The capsule lodged in three subjects (17 percent) with the 120 ml bolus and in 11 subjects (61 percent) with the 15 ml bolus. Esophageal manometry demonstrated a lower mean amplitude of esophageal contractions in subjects in whom the capsule lodged with the 120 ml bolus and in the elderly subjects. We conclude that the esophageal transit time of a gelatin capsule is related to the volume of fluid chaser. Our findings that a lower amplitude of esophageal contractions was associated with elderly patients and those in whom the capsule lodged with the large fluid bolus are worthy of further investigation.