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Light-guided tracheal intubation using a prototype illuminated flexible catheter through the intubating laryngeal mask.

We evaluated the efficacy of a newly developed prototype illuminated flexible catheter to facilitate tracheal intubation through the intubating laryngeal mask and compared this light-guided technique with the conventional blind tracheal intubation through the intubating laryngeal mask. The illuminated flexible catheter consists of a completely flexible thin plastic catheter, a bulb attached to its distal end, a 15-mm concentric adapter at its proximal end connected with a battery and a power switch. The device is placed into a silicone tracheal tube in such a way that the bulb protrudes from the distal end of the tracheal tube. One hundred adult patients, ASA I-III, scheduled to undergo propofol/fentanyl/atracurium anaesthesia for elective surgery were studied. All participants underwent a randomized double comparative cross over trial with respect to the tracheal intubation technique through the intubating laryngeal mask. The light guided tracheal intubation was performed as follows; the tracheal tube preloaded with the illuminated flexible catheter was inserted through the intubating laryngeal mask and by observing the glow in the neck was advanced into the trachea. Whenever resistance was felt during insertion, appropriate adjusting manoeuvres were performed. The intubating laryngeal mask was inserted successfully in all patients. The success rate for the blind and light-guided technique was 91% and 100%, respectively (P = 0.003). The mean (+/- SD) duration including appropriate intubating laryngeal mask placement and tracheal intubation, was significantly lower in the light-guided tracheal intubation technique, than with the blind tracheal intubation (31 +/- 8 s vs. 43 +/- 18 s; P < 0.0001). We conclude that the use of an illuminated flexible catheter carries advantages either in optimizing the intubating laryngeal mask position in the laryngopharynx or in achieving a quick and safe light-guided advancement from laryngopharynx into the trachea.

Adult↗

The performance of foreign medical graduates on the National Board of Medical Examiners (NBME) standardized patient examination prototype: a collaborative study of the NBME and the Educational Commission for Foreign Medical Graduates (ECFMG).

OBJECTIVES: The purpose of the study was to explore foreign medical graduates' (FMGs) performance on a clinical skills (SPX) examination. The National Board of Medical Examiners (NBME) is in the process of developing an SPX for potential use in the United States Medical Licensing Examination (USMLE). The Educational Commission for Foreign Medical Graduates (ECFMG) is developing the Clinical Skills Assessment (CSA) as an additional requirement for FMGs who wish to be certified by ECFMG. DESIGN: Thirty-three FMGs and 151 United States medical students (USMSs) took the SPX during the winter of 1996 as part of the ongoing pilot studies conducted by the NBME. Four clinical skill areas were assessed: history-taking, physical examination, communication and interpersonal skills. The examination used in this research consisted of 12 cases. The examination utilizes standardized patients (SPs) who are trained to document examinee behaviours and evaluate the communication component of the test. The SPs were also trained to evaluate the English proficiency of the candidates. Candidates were also administered the Test of Spoken English developed by the Educational Testing Services (ETS). SETTING: The examination was conducted in one medical school which served as an SPX centre for NBME pilot studies. SUBJECTS: Thirty-three foreign medical students and 151 US medical students. RESULTS: The indications were that the majority of candidates in both groups felt the examination was moderately fair but 78% of FMGs felt moderately pressed for time, vs. 80% of the USMSs who did not feel pressed for time. Reliabilities obtained for the various SPX components were somewhat higher for the FMGs reflecting the heterogeneity of this group. CONCLUSIONS: The NBME-ECFMG collaborative study yielded important information regarding the NBME SPX prototype as a performance measure for FMGs.

Clinical Competence↗

The monolithic fetal pacemaker: prototype lead design for closed thorax deployment.

Prenatal sudden cardiac death and hydrops fetalis are often due to complete heart block. However, no pacing modality exists for intrauterine application for fetal bradycardia. A prototype lead for a novel fetal pacemaker has been developed and used in a direct pacing model. It has been demonstrated that the lead can be safely and successfully deployed using a hypochondriac and transdiaphragmatic or subxiphoid approach. Pacing with ventricular capture was evident with the widening of QRS duration from 50.2 +/- 9.8 to 95.1 +/- 12.8 ms (P = 0.0001). Further studies by echocardiogram revealed an increase in the pulse with pacing, confirming pacing. This study documents proof-of-concept for closed thorax over-the-wire deployment of a novel lead design applicable to fetal pacing. By combining the lead design with microcircuitry and a small power source, it is possible to create a monolithic fetal pacemaker system capable of being deployed in utero.

Animals↗

A prototypic intracellular calcium antagonist, TMB-8, protects cultured cerebellar granule cells against the delayed, calcium-dependent component of glutamate neurotoxicity.

The effect(s) of a prototypic intracellular Ca2+ antagonist, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), on glutamate-induced neurotoxicity was investigated in primary cultures of mouse cerebellar granule cells. Glutamate evoked an increase in cytosolic free-Ca2+ levels ([Ca2+]i) that was dependent on the extracellular concentration of Ca2+ ([Ca2+]o). In addition, this increase in [Ca2+]i correlated with a decrease in cell viability that was also dependent on [Ca2+]o. Glutamate-induced toxicity, quantified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining, was shown to comprise two distinct components, an "early" Na+/Cl(-)-dependent component observed within minutes of glutamate exposure, and a "delayed" Ca(2+)-dependent component (ED50 approximately 50 microM) that coincided with progressive degeneration of granule cells 4-24 h after a brief (5-15 min) exposure to 100 microM glutamate. Quantitative analysis of cell viability and morphological observations identify a "window" in which TMB-8 (at > 100 microM) protects granule cells from the Ca(2+)-dependent, but not the Na+/Cl(-) -dependent, component of glutamate-induced neurotoxic damage, and furthermore, where TMB-8 inhibits glutamate-evoked increases in [Ca2+]i. These findings suggest that Ca2+ release from a TMB-8-sensitive intracellular store may be a necessary step in the onset of glutamate-induced excitotoxicity in granule cells. However, these conclusions are compromised by additional observations that show that TMB-8 (1) exhibits intrinsic toxicity and (2) is able to reverse its initial inhibitory action on glutamate-evoked increases in [Ca2+]i and subsequently effect a pronounced time-dependent potentiation of glutamate responses. Dantrolene, another putative intracellular Ca2+ antagonist, was completely without effect in this system with regard to both glutamate-evoked increases in [Ca2+]i and glutamate-induced neurotoxicity.

Animals↗

Genetic approaches in the clinical investigation of complex disorders: malnutrition, inflammation, and atherosclerosis (MIA) as a prototype.

Despite major research efforts and improvements in dialysis technology, patients with end-stage renal disease (ESRD) experience an extremely high mortality, which seems to be increasingly related to cardiovascular disease. Cardiovascular disease has been linked to the presence of systemic inflammation and malnutrition (MIA syndrome), in addition to the high prevalence of traditional risk factors observed in ESRD patients. Since the mechanisms underlying the development of these complications of ESRD are largely unknown, new strategies for identification of risk factors, pathophysiologic pathways, and targets for intervention are warranted. Although the combined impact of MIA complications seems to determine the extremely poor clinical outcome in the ESRD patients, there are significant unexplained individual differences in the development of the MIA syndrome, implying that genetic differences might play a role. The vast information generated by the advances in molecular genetics offers a great opportunity to analyze the causes of differences not only in our susceptibility to (or protection from) various diseases, but also in the age of onset, severity of illness, and in the way our bodies respond to treatment. In this review, we summarize an integrated approach in the investigation of complex disorders, requiring the interactive collaboration between laboratory, clinical, and epidemiologic resources using the MIA syndrome as a prototype. We focus on the application of common genetic variations (single nucleotide polymorphisms [SNPs]) in association with studies to generate potential risk profiling using data from multiple vulnerability genes. The appropriate application of this approach may be essential in the early identification of high-risk individuals and groups of patients for whom specific therapeutic interventions are indicated, thus creating a tailor-made clinical management for the future.

Arteriosclerosis↗

Computational flow study of the continuous flow ventricular assist device, prototype number 3 blood pump.

A computational fluid dynamics study of blood flow in the continuous flow ventricular assist device, Prototype No. 3 (CFVAD3), which consists of a 4 blade shrouded impeller fully supported in magnetic bearings, was performed. This study focused on the regions within the pump where return flow occurs to the pump inlet, and where potentially damaging shear stresses and flow stagnation might occur: the impeller blade passages and the narrow gap clearance regions between the impeller-rotor and pump housing. Two separate geometry models define the spacing between the pump housing and the impeller's hub and shroud, and a third geometry model defines the pump's impeller and curved blades. The flow fields in these regions were calculated for various operating conditions of the pump. Pump performance curves were calculated, which compare well with experimentally obtained data. For all pump operating conditions, the flow rates within the gap regions were predicted to be toward the inlet of the pump, thus recirculating a portion of the impeller flow. Two smaller gap clearance regions were numerically examined to reduce the recirculation and to improve pump efficiency. The computational and geometry models will be used in future studies of a smaller pump to determine increased pump efficiency and the risk of hemolysis due to shear stress, and to insure the washing of blood through the clearance regions to prevent thrombosis.

Computer Simulation↗

An in vitro biomechanical comparison of a prototype intramedullary pin-plate with a dynamic compression plate for equine metacarpophalangeal arthrodesis.

OBJECTIVES: To compare the biomechanical properties of a prototype intramedullary pin-plate (IMPP) implant specifically designed for equine metacarpophalangeal (MCP) arthrodesis with a dynamic compression plate (DCP) system. STUDY DESIGN: In vitro biomechanical testing of paired cadaveric equine forelimbs with a simulated traumatic disruption of the suspensory apparatus, stabilized by one of two methods for MCP arthrodesis. ANIMAL POPULATION: Twenty-one pairs of adult equine cadaveric forelimbs. METHODS: Each forelimb had the distal sesamoidean ligaments severed to create a disrupted suspensory apparatus. For each forelimb pair, the MCP joint was stabilized with the IMPP in one limb, and a DCP in the other limb. Seven matching limb pairs were tested in axial compression in a single cycle to failure, 7 matching limb pairs were tested in torsion in a single cycle to failure, and 7 matching limb pairs were fatigued tested in axial compression. Mean test variable values for each method were compared using a paired t-test within each group. Significance was set at P<.05. RESULTS: The mean yield load, yield stiffness, and failure load (axial compression, torsional loading) was significantly greater for the IMPP compared with the DCP system. Mean cycles to failure for axial compression was significantly greater for the IMPP compared with the DCP system. Significance in all tests was P<.0001. CONCLUSION: The IMPP was superior to the DCP system in resisting the biomechanical forces most likely to cause failure of MCP joint arthrodesis. CLINICAL RELEVANCE: The IMPP implant should be considered for MCP arthrodesis in horses with traumatic disruption of the suspensory apparatus. The specific design of the IMPP implant may facilitate equine MCP arthrodesis and avoid convalescent complications related to cyclic fatigue.

Animals↗

Clinical development of decitabine as a prototype for an epigenetic drug program.

This review highlights decitabine as a prototype epigenetic modifying drug to show how the clinical development of epigenetic agents differs from that of traditional cytotoxic chemotherapies. Decitabine, a cytosine analogue, is cytotoxic at high doses but has selective DNA demethylating activity at low doses. The focus of current decitabine investigations is twofold: to elucidate all of the mechanisms of action and to determine the optimal dose, schedule, and concomitant therapies. New phase I trials have identified a "biologically effective dose," which is 1 to 2 logs lower than the cytotoxic dose. A clinical development program with low-dose decitabine in malignant diseases is focused on myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML). A phase III trial in MDS showed objective responses (complete [CR] plus partial [PR] remission) and longer median time to progression to AML or death with decitabine than with supportive care alone. The optimal use of decitabine may be in combination with other agents that promote gene expression, namely, histone deacetylase (HDAC) inhibitors. Optimized decitabine doses and combinations with other epigenetic therapies that can be used at minimally toxic doses provide potentially safer therapeutic options and introduce novel combination therapies.

Antigens, Neoplasm↗

Tirapazamine: prototype for a novel class of therapeutic agents targeting tumor hypoxia.

Preclinical models in vitro and in vivo have shown that tumor hypoxia alters the malignant cell phenotype, selecting for p53 mutations, stimulating angiogenesis and metastasis, and markedly reducing the efficacy of both radiotherapy and chemotherapy. Similarly, clinical studies measuring pretreatment tumor oxygen status confirm that the presence of hypoxia confers a negative impact on local control, disease-free survival, and overall survival. Despite these data and extensive past research efforts, the promise of developing selective hypoxic-cell sensitizers has been largely unfulfilled. In contrast, tirapazamine is the rationally designed prototype for a new class of therapeutic agents targeting tumor hypoxia: hypoxic cytotoxins. Tirapazamine is bioreductively activated in hypoxic cells and has been shown to potentiate the cytotoxicity of radiation and a number of chemotherapeutic drug classes, in particular platinum compounds and taxanes. This article reviews the preclinical and clinical development of tirapazamine, as well as current trials in non-small cell lung cancer designed to provide proof of principle for this new category of cancer therapeutics.

Carcinoma, Non-Small-Cell Lung↗

Analysis of errors in medical rapid prototyping models.

Rapid prototyping (RP) is a relatively new technology that produces physical models by selectively solidifying UV-sensitive liquid resin using a laser beam. The technology has gained a great amount of attention, particularly in oral and maxillofacial surgery. An important issue in RP applications in this field is how to obtain RP models of the required accuracy. We investigated errors generated during the production of medical RP models, and identified the factors that caused dimensional errors in each production phase. The errors were mainly due to the volume-averaging effect, threshold value, and difficulty in the exact replication of landmark locations. We made 16 linear measurements on a dry skull, a replicated three-dimensional (3-D) visual (STL) model, and an RP model. The results showed that the absolute mean deviation between the original dry skull and the RP model over the 16 linear measurements was 0.62 +/- 0.35 mm (0.56 +/- 0.39%), which is smaller than values reported in previous studies. A major emphasis is placed on the dumb-bell effect. Classifying measurements as internal and external measurements, we observed that the effect of an inadequate threshold value differs with the type of measurement.

Algorithms↗

[Connections between attachment prototypes and relationship patterns].

Connections between attachment styles and relationship patterns are studied on 32 female psychotherapy patients. Our study gives first hints to a connection between attachment variables, assessed by the German version of the Adult Attachment Prototype Rating (AAPR) and predominant relationship patterns, assessed by the Core Conflictual Relationship Theme Method (CCRT) developed by Luborsky, if both methods are used independently. Subsamples according to the attachment styles show differences in CCRT variables.

Adult↗

Tissue engineering of vascular conduits: fabrication of custom-made scaffolds using rapid prototyping techniques.

BACKGROUND: The technique of stereolithography, which automatically fabricates models from X-ray computed tomography or magnetic resonance imaging (MRI) data linked to computer-aided design programs, has been applied to the fabrication of scaffolds for tissue engineering. We previously reported on the application of stereolithography in scaffold fabrication of a trileaflet heart valve. In our current experiment we demonstrate a new technique for the fabrication of custom-made conduits for the potential replacement of a coarcted aortic segment. METHODS AND RESULTS: In this experiment the image data derived from a 12-year-old male patient with aortic coarctation scanned by MRI were processed by a computer-aided design program to reconstruct the aortic arch with isthmus stenosis three dimensionally. By defining the stenotic section and the adjacent normal vessel a custom-made nonstenotic descending aorta was reconstructed to replace the stenosed part. The rapid prototyping technique was used to establish stereolithographic models for fabricating biocompatible and biodegradable vascular scaffolds with the anatomic structure of the recalculated human descending aorta through a thermal processing technique. CONCLUSION: Our results suggest that the re-creation and reproduction of complex vascular structures by computer-aided design techniques may be useful to fabricate custom-made polymeric scaffolds for the tissue engineering of living vascular prostheses.

Aortic Coarctation↗

Endoscopic resection of large colonic lipomas assisted by a prototype single-use Endoloop device.

Colonic lipomas are benign adipose tumors that occasionally cause symptoms. Endoscopic resection of large lipomas may be associated with the risk of hemorrhage or perforation. Experience with endoscopic resection of colonic lipomas with the assistance of a prototype single-use ligating Endoloop device, with a detachable snare unit, has not been previously reported. Three patients with a total of four large symptomatic colonic lipomas successfully underwent endoscopic resection with the aid of this device. One patient had self-limiting minor rectal bleeding which settled without consequence. All patients were well on follow-up, with resolution of their symptoms. This novel endoscopic technique should be considered during resection of large lipomas (> 10 mm diameter) to reduce the potential risk of bleeding.

Aged↗

Experimental phantom lesion detectability study using a digital breast tomosynthesis prototype system.

PURPOSE: To compare the sensitivity of conventional two-dimensional (2D) projection imaging with tomosynthesis with respect to the detectability of mammographic phantom lesions. MATERIALS AND METHODS: Using a breast tomosynthesis prototype based on a commercial FFDM system (Siemens MAMMOMAT Novation), but modified for a wide angle tube motion and equipped with a fast read-out amorphous selenium detector, we acquired standard 2D images and tomosynthesis series of projection views. We used the Wisconsin mammographic random phantom, model RMI 152A. The anode filter combinations Mo/Mo and W/Rh at two different doses were used as typical radiographic techniques. Slice images through the phantom parallel to the detector were reconstructed with a distance of 1 mm employing a filtered back-projection algorithm. The image data sets were read by five radiologists and evaluated with respect to the detectability of the phantom details. RESULTS: For all studied radiographic techniques, the detection rate in the tomosynthesis mode was 100 %, i. e. 75 true positive findings out of 75 possible hits. In contrast, the conventional projection mode yielded a detection rate between 80 and 93 % (corresponding to 60 and 70 detected details) depending on the dose and X-ray spectrum. CONCLUSION: Tomosynthesis has the potential to increase the sensitivity of digital mammography. Overlapping structures from out-of-plane tissue can be removed in the tomosynthesis reconstruction process, thereby enhancing the diagnostic accuracy.

Algorithms↗

Biliary stenting with a prototype expandable Teflon endoprosthesis.

BACKGROUND AND STUDY AIMS: A new balloon-expandable Teflon endoprosthesis was developed for endoscopic placement in the biliary tree. After deployment to its maximum diameter the stent is hardened by exposure to UV light. We present our preliminary results with a prototype 18 Fr prosthesis. PATIENTS AND METHODS: Three patients with a distal common bile duct obstruction due to unresectable pancreatic head carcinoma were treated with this stent. Insertion of the stent was the only palliative procedure. Patients were followed up until stent dysfunction or death. RESULTS: Stent placement was successful in all patients and no procedural complications occurred. Distal migration occurred in one patient, clogging of the stent after 149 days in another. CONCLUSION: In patients with a malignant biliary stricture this newly developed expandable endoprosthesis is effective in relieving obstructive jaundice. The technique has potential advantages over placement of current expandable metal mesh stents.

Aged↗

[A remote access system for inquiry of centrally stored data on patients suspected of malignant hyperthermia . A prototypical development for the Internet].

OBJECTIVES: Malignant hyperthermia (MH) is an inherited, potentially life-threatening syndrome of the skeletal muscles. It is a life-threatening complication of anaesthesia with a high mortality (8-10%). The risk of the patient during anaesthesia due to an overlooked predisposition for MH can be reduced by organisational measures, such as, all data of MH-susceptible patients and their families known in Germany must be brought together in a central register, MH-relevant data of patients must be readily retrievable, optional oral advice for those making an inquiry must be available. METHODS: To achieve this goal, a client-server system has been implemented: Standard Multimedia personal computers installed at the user's (anaesthetist's) site, linked to the Internet, will act as clients. On a server, relevant data of patients concerning MH-susceptibility are integrated in a central database. The newly developed software of this project ensures the legally prescribed data security on the server and the data routes. At the client's site, standard software together with automatically installed programmes from the server using Java applets ensure easy use and maintenance. IMPLEMENTATION: The total system was implemented and tested. Its functionality and high availability was demonstrated during this test period. Relevant aspects of data security were successfully examined by the data security officer of the University Hospitals of Baden-Württemberg. The user can optionally call a multifunctional teleconference which secures on-line advice if needed. This system demonstrates a safe and quick retrieval of MH relevant data of patients via Internet while at the same time guaranteeing all aspects of data protection and security. CONCLUSION: A prototypical database access system is described. It ensures safe access to patient data via Internet, while guaranteeing all aspects of data security.

Computer Communication Networks↗

[Prototype of an ophthalmoscope for studying an upright image with light amplification].

The instrument described here is the prototype of a direct ophthalmoscope with amplification of available light. The beam path has already been published and patented under reference number 3124305. It does not require drug-induced mydriasis, reduces light toxicity of the retina, and facilitates examination of pre-eclamptic and other patients who are sensitive to light. With this ophthalmoscope it may be possible to demonstrate the autofluorescence of the hyalocytes, described by Cremer-Bartels and Balacz.

Fluorescence↗

Prototype instruments for endoscopic microsurgery: technical note.

The authors describe a concept of converting microsurgical instruments into endoscopes and demonstrate prototype devices. These instruments combine the benefits of microsurgery (multiple instruments, tactile feedback, bimanual manipulation, magnification) with those of endoscopy (minimally invasiveness, indirect line of vision).

Animals↗