Aberrant platelet-derived growth factor alpha-receptor transcript as a diagnostic marker for early human germ cell tumors of the adult testis.

Testicular germ cell tumors are the most common form of cancer in young adult males. They result from a derangement of primordial germ cells, and they grow out from a noninvasive carcinoma-in-situ precursor. Since carcinoma in situ can readily be cured by low-dose irradiation, there is a great incentive for non- or minimally invasive methods for detection of carcinoma in situ. We have recently shown that human Tera-2 embryonal carcinoma cells, obtained from a nonseminomatous testicular germ cell tumor, show alternative splicing and alternative promoter use of the platelet-derived growth factor alpha-receptor gene, giving rise to a unique 1.5-kb transcript. In this study we have set up a reverse transcriptase-polymerase chain reaction strategy for characterization of the various transcripts for this receptor. Using this technique, we show that a panel of 18 seminomas and II nonseminomatous testicular germ cell tumors all express the 1.5-kb transcript. In addition, a panel of 27 samples of testis parenchyma with established carcinoma in situ were all found to be positive for the 1.5-kb transcript, while parenchyma lacking carcinoma in situ, placenta, and control semen were all negative. These data show that the 1.5-kb platelet-derived growth factor alpha-receptor transcript can be used as a highly selective marker for detection of early stages of human testicular germ cell tumors.

The sutureless aortic valve at 1 year: A large multicenter cohort study

OBJECTIVE Sutureless aortic valve replacement (AVR) offers an alternative to standard AVR in aortic stenosis. This prospective, single-arm study aimed to demonstrate safety and effectiveness of a bovine pericardial sutureless aortic valve at 1 year. METHODS From February 2010 to September 2013, 658 patients (mean age 78.3 ± 5.6 years; 40.0% octogenarian; 64.4% female; mean Society of Thoracic Surgeons score 7.2 ± 7.4) underwent sutureless AVR in 25 European centers. Concomitant cardiac procedures were performed in 29.5% and minimally invasive cardiac surgery in 33.3%. RESULTS One-year site-reported event rates were 8.1% for all-cause mortality, 4.5% for cardiac mortality, 3.0% for stroke, 1.9% for valve-related reoperation, 1.4% for endocarditis, and 0.6% for major paravalvular leak. No valve thrombosis, migration, or structural valve deterioration occurred. New York Heart Association class improved at least 1 level in 77.5% and remained stable (70.4% New York Heart Association class I or II at 1 year). Mean effective orifice area was 1.5 ± 0.4 cm(2); pressure gradient was 9.2 ± 5.0 mm Hg. Left ventricular mass decreased from 138.5 g/m(2) before surgery to 115.3 g/m(2) at 1 year (P < .001). Echocardiographic core laboratory findings confirmed that paravalvular leak was rare and remained stable during follow-up. CONCLUSIONS The Perceval sutureless valve resulted in low 1-year event rates in intermediate-risk patients undergoing AVR. New York Heart Association class improved in more than three-quarters of patients and remained stable. These data support the safety and efficacy to 1 year of the Perceval sutureless valve in this intermediate-risk population.

Essays on Entrepreneurship and Founder Pre-entry Knowledge

Thesis (Ph.D.)--University of Washington, 2016-06

Dog peritoneal and pleural cavities as bioreactors to grow autologous vascular grafts

Objective: The purpose of this study was to grow artificial blood vessels for autologous transplantation as arterial interposition grafts in a large animal model (dog). Method and results: Tubing up to 250 mm long, either bare or wrapped in biodegradable polyglycolic acid (Dexon) or nonbiodegradable polypropylene (Prolene) mesh, was inserted in the peritoneal or pleural cavity of dogs, using minimally invasive techniques, and tethered at one end to the wall with a loose suture. After 3 weeks the tubes and their tissue capsules were harvested, and the inert tubing was discarded. The wall of living tissue was uniformly 1-1.5 mm thick throughout its length, and consisted of multiple layers of myofibroblasts and matrix overlaid with a single layer of mesothelium. The myofibroblasts stained for a-smooth muscle actin, vimentin, and desmin. The bursting strength of tissue tubes with no biodegradable mesh scaffolds was in excess of 2500 mm Hg, and the suture holding strength was 11.5 N, both similar to that in dog carotid and femoral arteries. Eleven tissue tubes were transplanted as interposition grafts into the femoral artery of the same dog in which they were grown, and were harvested after 3 to 6.5 months. Eight remained patent during this time. At harvest, their lumens were lined with endothelium-like cells, and wall cells stained for alpha-actin, smooth muscle myosin, desmin and smoothelin; there was also a thick adventitia containing vasa vasorum. Conclusion: Peritoneal and pleural cavities of large animals can function as bioreactors to grow myofibroblast tubes for use as autologous vascular grafts.

Laparoscopically-assisted resection rectopexy for rectal prolapse: Ten years' experience

PURPOSE: This study has been undertaken to audit a single-center experience with laparoscopically-assisted resection rectopexy for full-thickness rectal prolapse. The clinical Outcomes and long-term results were evaluated. METHODS: The data were prospectively collected for the duration of the operation, time to passage of flatus postoperatively, hospital stay, morbidity, and mortality. For follow-up, patients received a questionnaire or were contacted. The data were divided into quartiles over the study period, and the differences in operating time and length of hospital stay were tested using the Kruskal-Wallis test. RESULTS: Between March 1992 and October 2003, a total of 117 patients underwent laparoscopic resection rectopexy for rectal prolapse. The median operating time during the first quartile (representing the early experience) was 180 minutes compared with 110 minutes for the fourth quartile (Kruskal-Wallis test for operating time = 35.523, 3 df, P < 0.0001). Overall morbidity was 9 percent (ten patients), with one death (< 1 percent). One patient had a ureteric injury requiring conversion. One minor anastomotic leak Occurred, necessitating laparoscopic evacuation of a pelvic abscess. Altogether, 77 patients were available for follow-up. The median follow-up was 62 months. Eighty percent of the patients reported alleviation of their symptoms after the operation. Sixty-nine percent of the constipated patients experienced an improvement in bowel frequency. No patient had new or worsening symptoms of constipation after Surgery. Two (2.5 percent) patients had full-thickness rectal prolapse recurrence. Mucosal prolapse recurred in 14 (18 percent) patients. Anastomotic dilation was performed for stricture in five (4 percent) patients. CONCLUSIONS: Laparoscopically-assisted resection rectopexy for rectal prolapse provides a favorable functional outcome and low recurrence rate. Shorter operating time is achieved with experience. The minimally invasive technique benefits should be considered when offering rectal prolapse patients a transabdominal approach for repair, and emphasis should now be on advanced training in the laparoscopic approach.

Electropermanent magnetic anchoring for surgery and endoscopy

The use of magnets for anchoring of instrumentation in minimally invasive surgery and endoscopy has become of increased interest in recent years. Permanent magnets have significant advantages over electromagnets for these applications; larger anchoring and retraction force for comparable size and volume without the need for any external power supply. However, permanent magnets represent a potential hazard in the operating field where inadvertent attraction to surgical instrumentation is often undesirable. The current work proposes an interesting hybrid approach which marries the high forces of permanent magnets with the control of electromagnetic technology including the ability to turn the magnet OFF when necessary. This is achieved through the use of an electropermanent magnet, which is designed for surgical retraction across the abdominal and gastric walls. Our electropermanent magnet, which is hand-held and does not require continuous power, is designed with a center lumen which may be used for trocar or needle insertion. The device in this application has been demonstrated successfully in the porcine model where coupling between an intraluminal ring magnet and our electropermanent magnet facilitated guided insertion of an 18 Fr Tuohy needle for guidewire placement. Subsequent investigations have demonstrated the ability to control the coupling distance of the system alleviating shortcomings with current methods of magnetic coupling due to variation in transabdominal wall thicknesses. With further refinement, the magnet may find application in the anchoring of endoscopic and surgical instrumentation for minimally invasive interventions in the gastrointestinal tract.

Live volumetric (4D) visualization and guidance of in vivo human ophthalmic surgery with intraoperative optical coherence tomography.

Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon's capabilities.

C-MEMS Based Micro Enzymatic Biofuel Cells

Miniaturized, self-sufficient bioelectronics powered by unconventional micropower may lead to a new generation of implantable, wireless, minimally invasive medical devices, such as pacemakers, defibrillators, drug-delivering pumps, sensor transmitters, and neurostimulators. Studies have shown that micro-enzymatic biofuel cells (EBFCs) are among the most intuitive candidates for in vivo micropower. In the fisrt part of this thesis, the prototype design of an EBFC chip, having 3D intedigitated microelectrode arrays was proposed to obtain an optimum design of 3D microelectrode arrays for carbon microelectromechanical systems (C-MEMS) based EBFCs. A detailed modeling solving partial differential equations (PDEs) by finite element techniques has been developed on the effect of 1) dimensions of microelectrodes, 2) spatial arrangement of 3D microelectrode arrays, 3) geometry of microelectrode on the EBFC performance based on COMSOL Multiphysics. In the second part of this thesis, in order to investigate the performance of an EBFC, behavior of an EBFC chip performance inside an artery has been studied. COMSOL Multiphysics software has also been applied to analyze mass transport for different orientations of an EBFC chip inside a blood artery. Two orientations: horizontal position (HP) and vertical position (VP) have been analyzed. The third part of this thesis has been focused on experimental work towards high performance EBFC. This work has integrated graphene/enzyme onto three-dimensional (3D) micropillar arrays in order to obtain efficient enzyme immobilization, enhanced enzyme loading and facilitate direct electron transfer. The developed 3D graphene/enzyme network based EBFC generated a maximum power density of 136.3 μWcm-2 at 0.59 V, which is almost 7 times of the maximum power density of the bare 3D carbon micropillar arrays based EBFC. To further improve the EBFC performance, reduced graphene oxide (rGO)/carbon nanotubes (CNTs) has been integrated onto 3D mciropillar arrays to further increase EBFC performance in the fourth part of this thesisThe developed rGO/CNTs based EBFC generated twice the maximum power density of rGO based EBFC. Through a comparison of experimental and theoretical results, the cell performance efficiency is noted to be 67%.

Aortic valve replacement through the upper ministernotomy. Preliminary experience with modified technique

Minimally invasive approach for aortic valve surgery has been developed since 1995, reducing the complications related to the full sternotomy. We have introduced a new method for central cannulation that reduces the length of surgical incision for the aortic valve replacement through upper mini-sternotomy. To improve the surgical view without enlargement of the incision, two small additional incisions are performed for both arterial and atrial cannulation. We have used the modified technique in 60 patients without sternal infection or other surgical complications and with good cosmetic results. Cardiac surgery - Aortic valve replacement - Minimally invasive approach.

Colonic lipomas. Three surgical techniques for three different clinical cases

Colonic lipomas larger than 2 cm in diameter are likely to be symptomatic. In some cases a complication is the first clinical sign. Massive lower intestinal bleeding or obstruction, acute bleeding, prolapse or perforation or, rarely, acute intussusception with intestinal obstruction require urgent surgery. Diagnosis is often made following colonoscopy, which can also have a therapeutic role. Imaging procedures such as CT has a secondary role. Patients with small asymptomatic colonic lipomas need regular follow up. For larger (diameter > 2 cm) and/or symptomatic lipomas, resection should be considered, although the choice between endoscopic or surgical resection remains controversial. We believe that even lipomas > 2 cm can safely be removed by endoscopic resection. If surgery is indicated, we consider laparoscopy to be the ideal approach in all patients for whom minimally invasive surgery is not contraindicated.

Prevenção da reabsorção óssea alveolar após extração dentária

Introdução: O processo alveolar é o conjunto de osso que se encontra em redor da raiz do dente. Este osso é sensível a uma variedade de fatores ambientais e fisiológicos que influenciam a sua integridade e o seu funcionamento. Como tal, a sua formação assim como a sua preservação é dependente da presença contínua do dente. A reabsorção do processo alveolar após extração dentária é uma consequência natural e fisiológica indesejável, que pode dificultar a colocação de um implante dentário na posição desejada. Com o aumento cada vez mais das demandas estéticas em medicina dentária, torna-se, portanto, necessário prevenir que a reabsorção óssea provoque este defeito na arcada dentária. Objetivos: Realizar uma revisão bibliográfica sobre as várias técnicas e materiais para preservação do rebordo alveolar, a fim de prevenir ou minimizar a reabsorção alveolar após extração dentária. Material e Métodos: A pesquisa foi realizada nas bases de dados Pubmed, B-on e Scielo, não foi aplicado nenhum limite temporal, e os critérios de inclusão foram artigos em língua inglesa e portuguesa. Num total de 164 artigos, selecionaram-se 82 estritamente relacionados com o tema. Os artigos excluídos desviavam-se do objetivo do trabalho ou eram inconclusivos. Selecionaram-se, também, capítulos do livro Clinical Periodontology and Implant Dentistry Volume 1 e 2, dos autores Niklaus P.Lang e Jan Lindhe. Desenvolvimento: De modo a compreender como o processo alveolar reabsorve, deve-se ter em conta as várias técnicas que se podem realizar para permitir uma boa quantidade de osso remanescente na arcada adequada a cada caso para uma possível reabilitação. As técnicas de preservação do osso alveolar após extração passam pela realização de técnicas cirúrgicas minimamente invasivas, estabilização do coágulo pelo princípio da cicatrização por primeira intenção usando membranas ou retalhos, preenchimento do alvéolo dentário com materiais de enxerto ou substitutos ósseos, terapias combinadas com a colocação de implantes imediatos e o recurso a células e fatores de crescimento. Conclusão: A preservação alveolar tem grande importância para uma posterior reabilitação oral com implantes com maior quantidade de osso disponível do que quando não é feita qualquer tipo de preservação. A extração das peças dentárias deve ser feita com cuidado para preservar ao máximo ou não danificar as superfícies ósseas remanescentes. É aconselhado que o encerramento da ferida seja por primeira intenção e que proporcione estabilidade ao coágulo, podendo ser usado retalhos ou mesmo membranas. O uso de enxertos ósseos tem uma importante função de proporcionar uma matriz para o coágulo se formar e promover o processo de cicatrização. O método de implante imediato, para além de ser bastante usado, tem como finalidade o conforto para o paciente de não ser submetido a uma posterior cirurgia para colocação do mesmo e, simultaneamente, mantem a estabilidade dos tecidos moles. Ainda uma técnica menos usada é com células e fatores de crescimento que proporciona uma cicatrização mais rápida e um aumento do potencial regenerativo dos tecidos.

Impact of radiofrequency ablation for patients with varicose veins on the budget of the German statutory health insurance system

Objectives: In contrast to other countries, surgery still represents the common invasive treatment for varicose veins in Germany. However, radiofrequency ablation, e.g. ClosureFast, becomes more and more popular in other countries due to potential better results and reduced side effects. This treatment option may cause less follow-up costs and is a more convenient procedure for patients, which could justify an introduction in the statutory benefits catalogue. Therefore, we aim at calculating the budget impact of a general reimbursement of ClosureFast in Germany. Methods: To assess the budget impact of including ClosureFast in the German statutory benefits catalogue, we developed a multi-cohort Markov model and compared the costs of a “World with ClosureFast” with a “World without ClosureFast” over a time horizon of five years. To address the uncertainty of input parameters, we conducted three different types of sensitivity analysis (one-way, scenario, probabilistic). Results: In the Base Case scenario, the introduction of the ClosureFast system for the treatment of varicose veins saves costs of about 19.1 Mio. € over a time horizon of five years in Germany. However, the results scatter in the sensitivity analyses due to limited evidence of some key input parameters. Conclusions: Results of the budget impact analysis indicate that a general reimbursement of ClosureFast has the potential to be cost-saving in the German Statutory Health Insurance.

Surface acoustic wave streaming in a PDMS microfluidic system: effect of frequency and fluid geometry & A remote ultrasonic glucose sensor

This thesis describes two separate projects. The first is a theoretical and experimental investigation of surface acoustic wave streaming in microfluidics. The second is the development of a novel acoustic glucose sensor. A separate abstract is given for each here. Optimization of acoustic streaming in microfluidic channels by SAWs Surface Acoustic Waves, (SAWs) actuated on flat piezoelectric substrates constitute a convenient and versatile tool for microfluidic manipulation due to the easy and versatile interfacing with microfluidic droplets and channels. The acoustic streaming effect can be exploited to drive fast streaming and pumping of fluids in microchannels and droplets (Shilton et al. 2014; Schmid et al. 2011), as well as size dependant sorting of particles in centrifugal flows and vortices (Franke et al. 2009; Rogers et al. 2010). Although the theory describing acoustic streaming by SAWs is well understood, very little attention has been paid to the optimisation of SAW streaming by the correct selection of frequency. In this thesis a finite element simulation of the fluid streaming in a microfluidic chamber due to a SAW beam was constructed and verified against micro-PIV measurements of the fluid flow in a fabricated device. It was found that there is an optimum frequency that generates the fastest streaming dependent on the height and width of the chamber. It is hoped this will serve as a design tool for those who want to optimally match SAW frequency with a particular microfluidic design. An acoustic glucose sensor Diabetes mellitus is a disease characterised by an inability to properly regulate blood glucose levels. In order to keep glucose levels under control some diabetics require regular injections of insulin. Continuous monitoring of glucose has been demonstrated to improve the management of diabetes (Zick et al. 2007; Heinemann & DeVries 2014), however there is a low patient uptake of continuous glucose monitoring systems due to the invasive nature of the current technology (Ramchandani et al. 2011). In this thesis a novel way of monitoring glucose levels is proposed which would use ultrasonic waves to ‘read’ a subcutaneous glucose sensitive-implant, which is only minimally invasive. The implant is an acoustic analogy of a Bragg stack with a ‘defect’ layer that acts as the sensing layer. A numerical study was performed on how the physical changes in the sensing layer can be deduced by monitoring the reflection amplitude spectrum of ultrasonic waves reflected from the implant. Coupled modes between the skin and the sensing layer were found to be a potential source of error and drift in the measurement. It was found that by increasing the number of layers in the stack that this could be minimized. A laboratory proof of concept system was developed using a glucose sensitive hydrogel as the sensing layer. It was possible to monitor the changing thickness and speed of sound of the hydrogel due to physiological relevant changes in glucose concentration.

Sistema colaborativo para monitoramento remoto de equipamentos biomédicos para a videolaparoscopia através do framework web-engineering e o padrão MVC sistema vera-3C

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Tecnologia, Departamento de Engenharia Mecânica, 2015.

A systems approach to cardiovascular health and disease with a focus on aortic wave dynamics

Cardiovascular diseases (CVDs) have reached an epidemic proportion in the US and worldwide with serious consequences in terms of human suffering and economic impact. More than one third of American adults are suffering from CVDs. The total direct and indirect costs of CVDs are more than $500 billion per year. Therefore, there is an urgent need to develop noninvasive diagnostics methods, to design minimally invasive assist devices, and to develop economical and easy-to-use monitoring systems for cardiovascular diseases. In order to achieve these goals, it is necessary to gain a better understanding of the subsystems that constitute the cardiovascular system. The aorta is one of these subsystems whose role in cardiovascular functioning has been underestimated. Traditionally, the aorta and its branches have been viewed as resistive conduits connected to an active pump (left ventricle of the heart). However, this perception fails to explain many observed physiological results. My goal in this thesis is to demonstrate the subtle but important role of the aorta as a system, with focus on the wave dynamics in the aorta.

The operation of a healthy heart is based on an optimized balance between its pumping characteristics and the hemodynamics of the aorta and vascular branches. The delicate balance between the aorta and heart can be impaired due to aging, smoking, or disease. The heart generates pulsatile flow that produces pressure and flow waves as it enters into the compliant aorta. These aortic waves propagate and reflect from reflection sites (bifurcations and tapering). They can act constructively and assist the blood circulation. However, they may act destructively, promoting diseases or initiating sudden cardiac death. These waves also carry information about the diseases of the heart, vascular disease, and coupling of heart and aorta. In order to elucidate the role of the aorta as a dynamic system, the interplay between the dominant wave dynamic parameters is investigated in this study. These parameters are heart rate, aortic compliance (wave speed), and locations of reflection sites. Both computational and experimental approaches have been used in this research. In some cases, the results are further explained using theoretical models.

The main findings of this study are as follows: (i) developing a physiologically realistic outflow boundary condition for blood flow modeling in a compliant vasculature; (ii) demonstrating that pulse pressure as a single index cannot predict the true level of pulsatile workload on the left ventricle; (iii) proving that there is an optimum heart rate in which the pulsatile workload of the heart is minimized and that the optimum heart rate shifts to a higher value as aortic rigidity increases; (iv) introducing a simple bio-inspired device for correction and optimization of aortic wave reflection that reduces the workload on the heart; (v) deriving a non-dimensional number that can predict the optimum wave dynamic state in a mammalian cardiovascular system; (vi) demonstrating that waves can create a pumping effect in the aorta; (vii) introducing a system parameter and a new medical index, Intrinsic Frequency, that can be used for noninvasive diagnosis of heart and vascular diseases; and (viii) proposing a new medical hypothesis for sudden cardiac death in young athletes.