bluuebunny/crossref_metadata_2025 huggingface dataset:
Psoriasis induced by topical imiquimod
Authors: Wu Jason K , Siller Greg , Strutton Geoff
Published: December 2004

We report the provocation of localized psoriasis at the sites of application of topical imiquimod, possibly evolving into a generalized flare. A patient with pre‐existing psoriasis that had been stable for 14 years was treated with imiquimod 5% cream daily for 6 weeks to three superficial basal cell carcinomas. During treatment one of the lesions developed severe local skin reactions necessitating rest periods, and received only 18 applications in 6 weeks. The other two lesions were treated for all 42 days. Psoriasiform changes developed at all three application sites. Nine‐and‐a‐half weeks after completing treatment the patient developed disseminated small psoriatic lesions. Other recognized triggers of psoriasis were not identified. The psoriasis resolved slowly with conventional treatment.
Granulomas in common variable immunodeficiency: A diagnostic dilemma
Authors: Lun Karyn R , Wood Dominic J , Muir James B , Noakes Rowland
Published: December 2004

A 60‐year‐old man with common variable immunodeficiency presented with a 7‐year history of violaceous plaques and papules on the thighs, arms and trunk. In the preceding 2 years he had developed new lesions on both hands. He had been previously diagnosed with sarcoidosis on the basis of skin and visceral histology, but subsequent opinion was that these were sarcoid‐like granulomas rather than being representative of true sarcoidosis. Biopsy of the hand lesions showed necrotizing granulomas, and a single acid‐fast bacillus (AFB) was identified on Wade–Fite stain. Subsequent repeat tissue biopsies for histology, culture and polymerase chain reaction testing failed to confirm the presence of mycobacterial organisms and it was felt that the organism was a contaminant introduced during tissue processing. The hand lesions responded well to intralesional injections of triamcinolone acetonide 10 mg/mL and oral tetracycline 500 mg b.d. was later introduced with a good clinical response. The diagnostic dilemma of finding granulomatous inflammation in a patient with common variable immunodeficiency, and the significance of a single AFB on histology are discussed. The treatment of sarcoid‐like granulomas with tetracycline therapy is also commented on.
Severe contact dermatitis as a result of an antiseptic bath oil
Authors: Storer Emma , Koh Karen J , Warren Lachlan
Published: December 2004

Siblings aged 7 and 5 years developed extensive truncal and flexural inflammation and desquamation unresponsive to standard eczema therapy. After delays in diagnosis, subsequent history revealed prior use of an antiseptic bath oil in a much stronger concentration than recommended. The case illustrates the severe irritant contact dermatitis that can arise following inadequate dilution of antiseptic bath oils, presumably as a result of skin contact with benzalkonium chloride and triclosan. Features that may direct attention to such irritant dermatitis are flexural predominance with superficial desquamation and rapid improvement after avoidance of exposure to the antiseptic solution.
Morbidity and cost of atopic eczema in Australia
Authors: Jenner Nicole , Campbell Jan , Marks Robin
Published: December 2004

The severity, morbidity and financial costs of atopic eczema (AE) were assessed during a 1‐year prospective study of a cohort of 85 people aged 14–63 years (mean 36 years) with the disease. A dermatologist examined each participant using the Six Area Six Sign Atopic Dermatitis severity scoring system to classify severity. Participants completed a Dermatology Life Quality Index (DLQI), a Nottingham Eczema Severity Score (NESS) and an ongoing diary of health‐care consultations and treatment costs. Follow up by mail to each participant was conducted every 2 months and participants completed a NESS, a DLQI and a diary of costs incurred. The DLQI data revealed that 36% spent over 10 min per day applying treatments, 28% indicated that AE influenced the clothes they wore, 21% felt embarrassed by their skin and 15% reported problems with treatments. There appeared to be a relationship between increased morbidity and increased severity. The average annual out‐of‐pocket cost for products used for treatment was A$425, ranging from A$13.50 to over A$2000 per individual. The average out‐of‐pocket cost for medical consultations was A$120, ranging from zero to over A$800 per individual. Although there were concerns about the reproducibility of the severity and morbidity measures, the data showed that AE can have substantial effects both financially and from a personal perspective for those affected.
Retrospective review of teledermatology in the Waikato, 1997–2002
Authors: Oakley Amanda MM , Rennie Michael H
Published: December 2004

We reviewed scheduled interactive teledermatology consultations from 1997 to 2002 between the Department of Dermatology of Health Waikato in Hamilton and remote sites at Taumarunui Hospital, Taupo Health Centre and the Ranolf Medical Centre, Rotorua, in New Zealand. Eighty‐five per cent of 384 appointments were attended and most non‐attendances were unexplained. The reason for consulting a dermatologist was inflammatory skin disease in 74% of cases, cutaneous infection in 10%, a skin lesion in 12% and no diagnosis was made in 4%. Follow ups were arranged for 41%, mainly by telemedicine (74%). Despite the apparent success of 75% of consultations and positive feedback from patients attending them, the service has not proved sustainable long‐term. This is because of other priorities for the delivery of health care, lack of support by clinicians and administrators, and ongoing financial costs.
Dermatofibrosarcoma protuberans: A clinicopathological analysis of 10 cases in Asians
Authors: Tan Audrey WH , Tan Suat Hoon
Published: December 2004

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive cutaneous neoplasm that exhibits a marked tendency for recurrence after local excision. This case series aims to study the clinical, histological and immunohistochemical features of DFSP in Asians. Ten patients with DFSP diagnosed between 1992 and 2001 were reviewed. There were more women than men in a ratio of 4:1. There were six Chinese, two Malays, one Indian and one Eurasian. The mean age was 38 years. The duration of each lesion before excision varied from 6 months to 27 years. Fifty per cent of tumours occurred on the trunk. On histology, all the lesions were dermal‐centred spindle cell tumours, extending to the subcutis, and exhibited the characteristic storiform pattern. One tumour also demonstrated fibrosarcomatous changes. Two tumours were of the rare pigmented variant (Bednar tumour). Immunohistochemistry with CD34 was positive in all cases, except the fibrosarcomatous area of one tumour, which was negative for CD34. For comparison, six cases of deep‐penetrating dermatofibroma were stained for CD34 and all showed an absence of CD34 expression. Wide excision of the tumour was performed in all cases of DFSP. There was no recurrence after mean follow up of 6 years (range 2.25–9.5 years).
Periodic painful purpura: Fact or factitious?
Authors: Vun Yin Y , Muir James
Published: December 2004

A 60‐year‐old woman with multiple psychosocial issues presented with a history of spontaneous painful bruising on her left upper arm. Extensive investigations did not reveal any abnormality apart from an elevated activated partial thromboplastin time as a result of factor XII deficiency. An autoerythrocyte sensitization test reproduced the tender bruises on her back. Our patient reported relief of pain with promethazine injections. She was subsequently referred to the psychiatric team for ongoing assessment and management. Having an awareness of this rare condition will assist in the prevention of unnecessary investigation of such cases and will allow the early referral of patients for appropriate psychological counselling.
Allergic contact dermatitis caused by the clothing dye, disperse blue 106, an important contact allergen that may be frequently missed
Authors: Dawes‐Higgs Elizabeth , Freeman Susanne
Published: December 2004

A 43‐year‐old woman presented with a history of dermatitis in a somewhat linear pattern under her breasts, across her back and around her waist. This dermatitis occurred after wearing a new blue dress with a blue lining. Patch testing showed an allergy to disperse blue 106 dye and also to her dress lining. However, she was not positive to p‐phenylene‐diamine, a dye in the standard patch test series. We recommend that any patient even slightly suspected of having an allergy to a textile dye should be tested with disperse blue, in addition to the standard series.
Outcomes of a nurse‐led telephone triage service in Australia
Authors: Keatinge Diana , Rawlings Kate
Published: December 2004

This paper reports on a study which comprised the first comprehensive evaluation of the Kids Kare Line telephone triage service in which experienced registered nurses respond to parents’ requests for health‐care advice for their child. This service is located in an acute care hospital in regional New South Wales, Australia. One hundred and one parents who telephoned the Kids Kare Line responded to a telephone‐administered survey designed to determine the service's efficiency and effectiveness. Responses demonstrated that parents sought advice about a range of issues, of which the management of fever was the most frequent. All but five parents considered their call to have been answered promptly, all parents understood the advice provided to them and 96% of parents were satisfied with this advice. Fifty parents identified that they had not used another service or health practitioner for the same issue subsequent to their Kids Kare Line telephone call.
A focus for nursing intervention: Realistic acceptance or helping illusions?
Authors: Côté José K , Pepler Carolyn
Published: December 2004

Despite having a life‐threatening disease, some people decide to live every remaining moment with intensity. Although they have accepted that their deaths might be imminent, they do not dwell on the possibility. They choose life and are sustained by vivid thoughts and inspirations. What can a nurse do to nourish such thoughts? Traditional theories of grief and loss maintain that one way to adjust to advanced stages of progressive disease is to accept death and prepare for it. Is it possible that these theories are simplistic and limiting in their assumptions about the way people ‘work through’ the stage of adjusting to loss? This article is a critical reflection of the process.
Simultaneous bilateral percutaneous nephrolithotomy in children
Authors: Salah Morshed A. , Tállai Béla , Holman Endre , Khan Munim A. , Tóth György , Tóth Csaba
Published: December 2004

In the paediatric section, two papers relating to the upper urinary tract are presented. The first, from Hungary, describes simultaneous bilateral percutaneous nephrolithotomy in 13 patients, where it was deemed feasible; this is the first such report. Authors from London report on unilateral nephrectomy in patients with nephrogenic hypertension, and found that it was successful in normalising blood pressure in patients with renal hypertension with a normal contralateral kidney.

OBJECTIVE

To evaluate the efficacy of removing bilateral kidney stones simultaneously from children, in one session.

PATIENTS AND METHODS

Thirteen patients (three girls and 10 boys, 26 kidneys; mean age 8 years, range 3–14) underwent simultaneous bilateral percutaneous nephrolithotomy (PCNL) in the same session, under general anaesthesia, starting with ureteric catheter insertion into both kidneys and using a 26 F adult nephroscope. The mean (range) stone diameter was 2 (1–3.5) cm. Three patients had staghorn stones in one of their kidneys. Ultrasonic disintegration was used; two patients had bilateral and two others unilateral endopylotomy, and one patient had percutaneous suprapubic cystolithotomy in the same session. The mean (range) operative duration was 65 (55–90) min.

RESULTS

All patients were rendered stone‐free; there was no severe bleeding or any other complication. On one side in one of the patients, a second session was needed because of residual stone. The nephrostomy tubes were removed 3 and 4 days after PCNL and the hospital stay was 6 (1–11) days.

CONCLUSION

The advantages of simultaneous bilateral PCNL are reduced psychological stress, one cystoscopy and anaesthesia, less medication and a shorter hospital stay and convalescence, with considerable savings in cost. In experienced hands this method can be used not only in adults but also in children. To our knowledge this is the only report of this technique in children.
Comparison of bipolar transurethral resection of the prostate with standard transurethral prostatectomy: shorter stay, earlier catheter removal and fewer complications
Authors: Starkman Jonathan S. , Santucci Richard A.
Published: December 2004

Authors from Detroit assess the use of the bipolar TURP against the monopolar technique; there were relatively few patients, reflecting the decreasing requirement for TURP in the USA. In addition, the amount of resected tissue was not particularly large, almost certainly a reflection of the decreasing size of resected prostatic tissue in that country. They found the bipolar TURP to have many advantages over standard monopolar TURP, and these are described.

Acute urinary retention is a common urological emergency, and authors from London found that it had a measurable impact on the health‐related quality of life of patients who develop this problem. They describe particularly how painful a condition it is, and that it had a significant economic burden.

OBJECTIVE

To assess bipolar transurethral prostatectomy (TURP) using the Gyrus system (Gyrus Medical, Maple Grove, MD) compared with a standard monopolar TURP.

PATIENTS AND METHODS

All 43 patients undergoing TURP from November 2000 to August 2002 were reviewed retrospectively; the 1.5‐year observation period allowed for the detection of late complications. In all, 18 consecutive patients had standard and 25 had bipolar TURP.

RESULTS

The resection was 18 g for standard and 15 g for the Gyrus TURP (part of the Gyrus chips are vaporized during resection). The Foley catheter was removed sooner (1.8 vs 3.2 days) and the hospital stay was less in the Gyrus group (1.2 vs 2.1 days). Acute complications occurred in a third of the standard group and four (16%) of the Gyrus group. Long‐term complications were comparable, at two each in the standard and Gyrus groups. Four patients (15%) with small glands went home on the day of surgery, needing no bladder irrigation after Gyrus TURP.

CONCLUSION

Few innovations in TURP technique have been described in the past few decades but comparing Gyrus to standard TURP showed that the former allows earlier removal of the urinary catheter and earlier discharge from hospital, while decreasing complications. The Gyrus system also has other benefits; it allows coagulation of tissue during resection, resulting in excellent intraoperative visualization, and normal saline is used as the irrigant fluid, reducing the potential for TUR syndrome. The shorter stay after Gyrus TURP can result in cost savings of up to $1200/patient/day at our institution.
Para‐Graph: Graph‐Based Parameterization of Triangle Meshes with Arbitrary Genus
Authors: Patanè Giuseppe , Spagnuolo Michela , Falcidieno Bianca
Published: December 2004

This paper describes a novel approach to the parameterization of triangle meshes representing 2‐manifolds with an arbitrary genus. A topology‐based decomposition of the shape is computed and used to segment the shape into primitives, which define a chart decomposition of the mesh. Then, each chart is parameterized using an extension of the barycentric coordinates method. The charts are all 0‐genus and can be of three types only, depending on the number of boundary components. The chart decomposition and the parameterization are used to define a shape graph where each node represents one primitive and the arcs code the adjacency relationships between the primitives. Conical and cylindrical primitives are coded together with their skeletal lines that are computed from and aligned with their parameterization. The application of the parameterization approach to remeshing guarantees that extraordinary vertices are localized only where two patches share a boundary and they are not scattered on the whole surface.
The Importance of Deviance in Intellectual Development
Authors: McKenzie Richard B. , Galar Roman
Published: December 2004

Abstract.  This paper seeks to explain the success of public choice at Virginia Tech in the 1970s in two ways. First, I reflect on my graduate school experience at Virginia Tech, with the intent of identifying particular characteristics of the people and location of Virginia Tech, including its remoteness, that facilitated the development of the paradigm shift that public choice, in the late 1960s and early 1970s, represented. Second, I argue that the success of public choice at Virginia Tech depended critically upon the willingness of the people here to disconnect from professional constraints and to think outside the conventional economics box. I make this point with the aid of a computer simulation of the evolutionary development of “people” (or “trials”) as they attempt to scale the highest “mountain” within a “mountain range,” the exact features of which (including the heights of the various “mountains”) are not known before the climb is started. In such an environment, finding the highest peak, the assumed goal, is critically dependent on a measure of “deviance,” or the willingness to shun short‐run opportunities of exploiting accepted methods.
Public Choice as an Academic Enterprise
Authors: Wagner Richard E.
Published: December 2004

Abstract.  This paper treats the development of public choice as an academic enterprise that originated at the University of Virginia and that grew to maturity at VPI. It seeks to distinguish between the particularistic and personal sources of programmatic success on the one hand, and institutional and organizational sources on the other. Only to the extent the success is institutional or organizational is there something that potentially can be duplicated through the adoption of an appropriate institutional framework. Otherwise the success is idiosyncratic, and must be attributed to the particular qualities of James Buchanan and Gordon Tullock, independently of the institutional and organizational framework.
Public Choice as an Academic Enterprise
Authors: Toma Eugenia F.
Published: December 2004

ABSTRACT.  The author writes of her experiences as a graduate student at Virginia Tech during the high productivity years of the public choice enterprise. She discusses peer effects on learning and productivity, and the environment created by the Buchanan and Tullock team and their colleagues. She notes that in the current competitive situation it may be difficult for institutions of higher learning to justify the immeasurable academic and intellectual benefits of groups similar to the Center for the Study of Public Choice in Blacksburg.
Life in the Putty‐Knife Factory!1
Authors: Brennan Geoffrey
Published: December 2004

ABSTRACT.  The public choice approach can be used to analyze a wide variety of social phenomena, of which academic activity is one possible example. The object of this paper is to see if the public choice approach can throw useful light on its own rise as a potent body of ideas in contemporary social sciences. The particular focus is a set of reminiscences about the life of the Public Choice Center over the period 1969 to 1983 (and especially 1976 to 1983, when I was myself part of the Center). Reflecting on that period, I attempt to isolate those features of the Center's life that seem to me to have been most important to its success; and then ask broader questions about how much of that success public choice methods might illuminate. The aspect of public choice theory that I focus on in this connection is its account of agent motivation. I assert that the desire for esteem played a greater role in motivating the agents than the desire for “interests,” more narrowly construed. The paper concludes with some general thoughts about esteem as a motivating factor in academic circles and more generally.
The Quest for Meaning in Public Choice
Authors: Ostrom Elinor , Ostrom Vincent
Published: December 2004

Abstract. The logical foundations of constitutional government are of basic importance if people are to be self‐governing. All forms of political order are Faustian bargains subject to numerous risks. If constitutional choice applies to all patterns of human association, the complexity of associated relationships and the potential threats to the viability of associated relationships in the aggregate exceed the limits of human cognition. The development of analytical capabilities depends on using frameworks, theories, and models for formulating hypotheses about conditions and consequences, undertaking diagnostic assessments, and conceptualizing and designing alternative possibilities. The relationship of ideas to deeds in an experimental epistemology is necessary to achieve a warrantable art and science of association.
Commentary on “The Quest for Meaning in Public Choice” by Elinor Ostrom and Vincent Ostrom
Authors: Michael C. Munger
Published: December 2004

ABSTRACT. The Ostroms have created a paper that goes to the very heart of the public choice enterprise. They suggest that we should conceive of the evolution of constitutional procedures and laws in analogy with biological evolution. One of the paper's central goals is to establish the logical foundations of political order. I take this goal seriously and compare explicitly the task of explaining order in biology and politics. In the case of biology, the task of evolutionary theory has been to give an account of why there are complex arrangements of genetic material called “organisms” (including humans, giraffes, and whales) rather than just a nutrient‐rich primordial ooze with no apparent structure. For the social scientist, the task is to explain why there are rules, structure, and stability in societies.
Bargaining with the Devil
Authors: Amadae S.M.
Published: December 2004

ABSTRACT. “Bargaining with the Devil: Commentary on the Ostroms’‘Quest for Meaning in Public Choice’” provides a commentary on Elinor Ostrom and Vincent Ostrom's paper, “The Quest for Meaning in Public Choice.” This discussion focuses on the challenging tension that exists between social scientific knowledge and social practices. It suggests that historical agents may have solved the dilemma of cooperation prior to rational choice theorists’ invention of the public goods problem.
A Toy Model of Scientific Progress
Authors: Lohmann Susanne
Published: December 2004

ABSTRACT. Scientific research programs have a life cycle consisting of a sequence of overlapping subprograms. Each subprogram works within set boundaries, driven by the internal logic of its theoretical and empirical puzzles; outside of the boundaries lie the blind spots of the subprogram. Over time, boundaries shift as the blind spots become hot spots of inquiry. For a while, the status‐quo subprogram overlaps with the subprogram challenging it, but eventually it is superceded. Change occurs through replacement (the market entry of Young Turks threatens the Establishment) rather than adaptation (the Establishment moves with the times). Scientific progress depends on society supporting scientists and scholars by giving them a “room of their own,” and it requires systematic methods, but the most important determinant is the structure of the scientific enterprise. For scientific progress to occur, the structure must allow scientists and scholars to form deeply specialized clusters and at the same time force cross‐fertilization across clusters.
When Hard Heads Collide
Authors: Lomasky Loren E.
Published: December 2004

ABSTRACT. In this article, Loren Lomasky begins with a firsthand account of some of the people he interacted with at the Center for the Study of Public Choice in Blacksburg and some of what he learned there. Aside from the revealing personal anecdotes, we learn something of the culture clash he experienced as a visiting fellow at the Center and about his introduction to intellectual activity as “blood sport.” Lomasky then reviews some of the strengths and weaknesses of public choice theory from a philosophical point of view and offers some suggestions. These primarily concern the theory's narrow focus on the material nature of interests. Finally, Lomasky offers techniques for including moral interests in the deliberations of decision makers.
What Public Choice and Philosophy Should Not Learn from One Another
Authors: Sugden Robert
Published: December 2004

ABSTRACT. Lomasky offers accounts of public choice and of political philosophy, in which these disciplines have complementary theories of motivation, and suggests that each discipline can learn something from the other. This note argues that these two theories of motivation share a common weakness: an a priori, non‐empirical mode of analysis. Political philosophy models human beings as rational moral agents; public choice theory treats individuals as rationally self‐ interested. Neither theory is concerned with the psychology of actual human motivation. This common feature facilitates the transfer of ideas between the two disciplines, but it limits the usefulness of both. There is more to political motivation than can be captured by theories of reason.
Prudence and Constitutional Rights
Authors: McClennen Edward F.
Published: December 2004

ABSTRACT. In The Calculus of Consent, Buchanan and Tullock argue for institutional safeguards to ensure maximal benefit for all members of a community against the potential tyranny of the majority. I extend this idea by introducing prudential concerns and argue that they ought to be factored into the decision making that constructs such safeguards. Specifically, I see the safeguarding of prudential concerns for all members of society as a matter that should be secured from the random fate of the political process by constitutional provisions.
Comments on McClennen's “Prudence and Constitutional Rights”
Authors: Pitt Joseph C.
Published: December 2004

ABSTRACT. In The Calculus of Consent, Buchanan and Tullock argue, among other things, that institutional safeguards are required to ensure maximal benefit for all members of a community against the potential tyranny of the majority. McClennen extends this idea by introducing prudential concerns and argues that they ought to be factored into the decision making that constructs such safeguards. Specifically, McClennen sees the safeguarding of prudential concerns for all members of society as a matter of distribution that should be secured from the random fate of the political process through constitutional means. His method for ensuring the constitutional mandate is to place the responsibility for achieving this result in the hands of the judiciary. I argue that there are two problems with his solution: (1) it is ahistorical; and (2) it assumes the judiciary is without politics.
Heraclitian Vespers
Authors: Buchanan James M.
Published: December 2004

ABSTRACT. Viewed retrospectively, the early research program in public choice was intellectually exciting, and especially as that program found its institutional home in Blacksburg, Virginia, in the 1970s and 1980s. The time was ripe for such a scientific development, and the events of the 1960s gave impetus to particular thrusts of the still‐emerging research agenda.
Dosimetric evaluation of the clinical implementation of the first commercial IMRT Monte Carlo treatment planning system at 6 MV
Authors: Heath Emily , Seuntjens Jan , Sheikh‐Bagheri Daryoush
Published: December 2004

In this work we dosimetrically evaluated the clinical implementation of a commercial Monte Carlo treatment planning software (PEREGRINE, North American Scientific, Cranberry Township, PA) intended for quality assurance (QA) of intensity modulated radiation therapy treatment plans. Dose profiles calculated in homogeneous and heterogeneous phantoms using this system were compared to both measurements and simulations using the EGSnrc Monte Carlo code for the 6 MV beam of a Varian CL21EX linear accelerator. For simple jaw‐defined fields, calculations agree within 2% of the dose at with measurements in homogeneous phantoms with the exception of the buildup region where the calculations overestimate the dose by up to 8%. In heterogeneous lung and bone phantoms the agreement is within 3%, on average, up to 5% for a field. We tested two consecutive implementations of the MLC model. After matching the calculated and measured MLC leakage, simulations of static and dynamic MLC‐defined fields using the most recent MLC model agreed to within 2% with measurements.
Development and clinical introduction of an inverse planning dose optimization by simulated annealing (IPSA) for high dose rate brachytherapy
Authors: Lessard Etienne
Published: December 2004

High dose rate brachytherapy is a promising radiation treatment modality that uses temporarily implanted catheters to deliver the curative dose directly in the tumor. A programmable robotic device (the afterloader) moves a single tiny radioactive source (192Ir) along the catheters using a flexible cable attached to the source. With this flexible system, a wide variety of dose distributions can be generated from a given implant simply by adjusting the length of time (dwell time) that the source dwells at any location within the implanted catheters (dwell position). The challenge is to select the optimal sequence of dwell times related to the unique clinical situation of each patient. This treatment‐planning problem can be formalized as a combinatorial optimization problem. The optimization algorithm presented in this thesis is conceived to perform this task. An inverse planning (IP) approach has been adopted to guide the optimization process. This means that the optimization is guided by clinical objectives described by means of dose constraints specified to each digitized anatomical structure. A simulated annealing (SA) optimization engine has been designed to solve this particular problem in a short time for clinical applications (about ). This inverse planning by simulated annealing (IPSA) algorithm has been successfully implanted in four institutions: UCSF(1), CHUQ(2), NIH(3), CAV(4). At the moment of writing this thesis, more than 300 patients have been treated at these institutions for a wide variety of anatomical sites. Clinical studies performed by clinicians using IPSA demonstrated that the algorithm produces superior treatment plans from a dosimetric point of view than the conventional method using geometrical optimization. IPSA improves the target dose coverage while minimizing the dose delivered to organs at risk and provides consistent results from one patient to another. Both dosimetric indices and overall procedure time were improved with the clinical introduction of IPSA.
Registration of central paths and colonic polyps between supine and prone scans in computed tomography colonography: Pilot study
Authors: Li Ping , Napel Sandy , Acar Burak , Paik David S. , Jeffrey R. Brooke , Beaulieu Christopher F.
Published: December 2004

Computed tomography colonography (CTC) is a minimally invasive method that allows the evaluation of the colon wall from CT sections of the abdomen/pelvis. The primary goal of CTC is to detect colonic polyps, precursors to colorectal cancer. Because imperfect cleansing and distension can cause portions of the colon wall to be collapsed, covered with water, and/or covered with retained stool, patients are scanned in both prone and supine positions. We believe that both reading efficiency and computer aided detection (CAD) of CTC images can be improved by accurate registration of data from the supine and prone positions. We developed a two‐stage approach that first registers the colonic central paths using a heuristic and automated algorithm and then matches polyps or polyp candidates (CAD hits) by a statistical approach. We evaluated the registration algorithm on 24 patient cases. After path registration, the mean misalignment distance between prone and supine identical anatomic landmarks was reduced from 47.08 to 12.66 mm, a 73% improvement. The polyp registration algorithm was specifically evaluated using eight patient cases for which radiologists identified polyps separately for both supine and prone data sets, and then manually registered corresponding pairs. The algorithm correctly matched 78% of these pairs without user input. The algorithm was also applied to the 30 highest‐scoring CAD hits in the prone and supine scans and showed a success rate of 50% in automatically registering corresponding polyp pairs. Finally, we computed the average number of CAD hits that need to be manually compared in order to find the correct matches among the top 30 CAD hits. With polyp registration, the average number of comparisons was 1.78 per polyp, as opposed to 4.28 comparisons without polyp registration.
Feasibility study of beam orientation class‐solutions for prostate IMRT
Authors: Schreibmann Eduard , Xing Lei
Published: December 2004

IMRT is being increasingly used for treatment of prostate cancer. In practice, however, the beam orientations used for the treatments are still selected empirically, without any guideline. The purpose of this work was to investigate interpatient variation of the optimal beam configuration and to facilitate intensity modulated radiation therapy (IMRT) prostate treatment planning by proposing a set of beam orientation class‐solutions for a range of numbers of incident beams. We used fifteen prostate cases to generate the beam orientation class‐solutions. For each patient and a given number of incident beams, a multiobjective optimization engine was employed to provide optimal beam directions. For the fifteen cases considered, the gantry angle of any of the optimized plans were all distributed within a certain range The angular distributions of the optimal beams were analyzed and the most selected directions are identified as optimal directions. The optimal directions for all patients are averaged to obtain the class‐solution. The class‐solution gantry angles for prostate IMRT were found to be: three beams (0°, 120°, 240°), five beams (35°, 110°, 180°, 250°, 325°), six beams (0°, 60°, 120°, 180°, 240°, 300°), seven beams (25°, 75°, 130°, 180°, 230°, 285°, 335°), eight beams (20°, 70°, 110°, 150°, 200°, 250°, 290°, 340°), and nine beams (20°, 60°, 100°, 140°, 180°, 220°, 260°, 300°, 340°). The level of validity of the class‐solutions was tested using an additional clinical prostate case by comparing with the individually optimized beam configurations. The difference between the plans obtained with class‐solutions and patient‐specific optimizations was found to be clinically insignificant.
Inverse treatment planning with adaptively evolving voxel‐dependent penalty scheme
Authors: Yang Yong , Xing Lei
Published: December 2004

In current inverse planning algorithms it is common to treat all voxels within a target or sensitive structure equally and use structure specific prescriptions and weighting factors as system parameters. In reality, the voxels within a structure are not identical in complying with their dosimetric goals and there exists strong intrastructural competition. Inverse planning objective function should not only balance the competing objectives of different structures but also that of the individual voxels in various structures. In this work we propose to model the intrastructural tradeoff through the modulation of voxel‐dependent importance factors and deal with the challenging problem of how to obtain a sensible set of importance factors with a manageable amount of computing. Instead of letting the values of voxel‐dependent importance to vary freely during the search process, an adaptive algorithm, in which the importance factors were tied to the local radiation doses through a heuristically constructed relation, was developed. It is shown that the approach is quite general and the EUD‐based optimization is a special case of the proposed framework. The new planning tool was applied to study a hypothetical phantom case and a prostate case. Comparison of the results with that obtained using conventional inverse planning technique with structure specific importance factors indicated that the dose distributions from the conventional inverse planning are at best suboptimal and can be significantly improved with the help of the proposed nonuniform penalty scheme.
Matrix metalloproteinase induction in fibrosis and fibrotic nodule formation due to silica inhalation
Authors: Scabilloni James F. , Wang Liying , Antonini James M. , Roberts Jenny R. , Castranova Vincent , Mercer Robert R.
Published: December 2004

Matrix metalloproteinases (MMPs) are the principle enzymes that initiate degradation of collagen. We examined the role of MMPs during alveolar wall fibrosis and fibrotic nodule formation from silica exposure. Rats were exposed to filtered air or 15 mg/m3silica by inhalation for 5 days/wk, 6 h/day. Lungs were preserved by intratracheal instillation of fixative at 20, 40, 60, 79, and 116 days of exposure. Additional groups were fixed after 20, 40, and 60 days of exposure followed by 36 days of recovery. The number of nodules, defined by a collagenous core and a bounding cell layer detached from the alveolar wall, was determined by morphometry. Lungs showed increased alveolar wall collagen and fibrotic nodules at 79 and 116 days of exposure with increased collagenase and gelatinase activity. The number of nodules per lung in exposed groups increased from 619 ± 447 at 40 days to 13,221 ± 1,096 at 116 days (means ± SE, n = 5). No nodules were seen in control lungs. Silica-exposed rats with a 36-day recovery in filtered air showed enhanced MMP activity over exposure to silica for the same duration with no recovery. MMP-2 and MMP-9 were significantly elevated in alveolar macrophages after 40-day exposure. Stromelysin expression was demonstrated in alveolar macrophages and cells within fibrotic nodules. TIMP-1 expression was not significantly altered. In summary, MMP activity was upregulated at 40 days of silica exposure and progressively increased during ensuing fibrotic responses. Early expression of stromelysin was found in fibrosing alveolar walls and fibrotic nodules.
Alteration of airway neuropeptide expression and development of airway hyperresponsiveness following respiratory syncytial virus infection
Authors: Dakhama Azzeddine , Park Jung-Won , Taube Christian , El Gazzar Mohamed , Kodama Taku , Miyahara Nobuaki , Takeda Katsuyuki , Kanehiro Arihiko , Balhorn Annette , Joetham Anthony , Loader Joan E. , Larsen Gary L. , Gelfand Erwin W.
Published: December 2004

The mechanisms by which respiratory syncytial virus (RSV) infection causes airway hyperresponsiveness (AHR) are not fully established. We hypothesized that RSV infection may alter the expression of airway sensory neuropeptides, thereby contributing to the development of altered airway function. BALB/c mice were infected with RSV followed by assessment of airway function, inflammation, and sensory neuropeptide expression. After RSV infection, mice developed significant airway inflammation associated with increased airway resistance to inhaled methacholine and increased tracheal smooth muscle responsiveness to electrical field stimulation. In these animals, substance P expression was markedly increased, whereas calcitonin gene-related peptide (CGRP) expression was decreased in airway tissue. Prophylactic treatment with Sendide, a highly selective antagonist of the neurokinin-1 receptor, or CGRP, but not the CGRP antagonist CGRP(8–37), inhibited the development of airway inflammation and AHR in RSV-infected animals. Therapeutic treatment with CGRP, but not CGRP(8–37) or Sendide, abolished AHR in RSV-infected animals despite increased substance P levels and previously established airway inflammation. These data suggest that RSV-induced airway dysfunction is, at least in part, due to an imbalance in sensory neuropeptide expression in the airways. Restoration of this balance may be beneficial for the treatment of RSV-mediated airway dysfunction.
Absence of host tumor necrosis factor receptor 1 attenuates manifestations of idiopathic pneumonia syndrome
Authors: Shukla Mayank , Yang Shuxia , Milla Carlos , Panoskaltsis-Mortari Angela , Blazar Bruce R. , Haddad Imad Y.
Published: December 2004

The interaction of TNF-α with TNF receptor 1 (TNFR1) activates several signal transduction pathways that lead to apoptosis or NF-κB-dependent inflammation and immunity. We hypothesized that host TNFR1 expression contributes to noninfectious lung injury and inflammation commonly observed after bone marrow transplantation (BMT), termed idiopathic pneumonia syndrome (IPS). C57BL/6 TNFR1-sufficient (TNFR1+/+) and -deficient (TNFR1−/−) mice were total body irradiated with or without cyclophosphamide conditioning and were given bone marrow plus IPS-inducing donor spleen T cells from B10.BR wild-type mice. TNFR1−/−recipient mice exhibited improved early post-BMT survival associated with decreased permeability edema. In addition, the low lung compliance measured in anesthetized, ventilated TNFR1+/+mice on day 7 after BMT was restored to baseline during TNFR1 deficiency. Importantly, bronchoalveolar lavage fluid (BALF) inflammatory cells from TNFR1−/−vs. TNFR1+/+mice generated less nitric oxide (·NO) and nitrating species and exhibited suppressed programmed cell death as assessed using flow cytometry. However, cellular infiltration and levels of proinflammatory cytokines and chemokines were generally higher in BALF collected on day 7 after BMT from TNFR1−/−compared with TNFR1+/+recipient mice. Our results support a major role of host TNFR1 in regulation of ·NO production and lung dysfunction after allogeneic BMT.
Pulmonary overexpression of IL-10 augments lung fibrosis and Th2 responses induced by silica particles
Authors: Barbarin Virginie , Xing Zhou , Delos Monique , Lison Dominique , Huaux Francois
Published: December 2004

Chronic inflammation and proinflammatory cytokines as well as T helper type 2 (Th2) cytokines have been involved in the pathogenesis of pulmonary injury and lung fibrosis. The actual role of IL-10 in lung fibrosis is still unclear because this cytokine has been identified as Th2 but possesses strong anti-inflammatory properties. To better dissect the potential role of IL-10 in silica-induced lung fibrosis, IL-10 was overexpressed in the lung of mice by adenoviral gene transfer during the inflammatory (administered at day − 1) or the fibrotic (administered at day + 30) stages of the disease. Pulmonary overexpression of IL-10 during both silica-induced lung inflammation and fibrosis exacerbated the fibrotic lesions as estimated by the measurement of hydroxyproline and other biochemical and histological markers. Increased expression of IL-10 significantly enhanced the number of lung lymphocytes and bronchoalveolar lavage fluid IgG1 but not IgG2a levels, indicating the induction of a Th2-like immune response. In addition, the production of the profibrotic Th2 cytokines IL-4 and IL-13 was also significantly increased upon IL-10 overexpression. No difference in transforming growth factor-β or PGE2production was noted after adenoviral IL-10 treatment of silica-treated mice. Together, these data indicate that the increased expression of IL-10 significantly contributed to silica-induced lung fibrosis by exacerbating the Th2 response and the production of the profibrotic cytokines IL-4 and IL-13.
Cooperative anti-influenza activities of respiratory innate immune proteins and neuraminidase inhibitor
Authors: White Mitchell R. , Crouch Erika , van Eijk Martin , Hartshorn Max , Pemberton Lily , Tornoe Ida , Holmskov Uffe , Hartshorn Kevan L.
Published: December 2004

The surfactant collectins, surfactant proteins A and D (SP-A and D), and scavenger receptor-rich glycoprotein 340 (gp340) inhibit influenza A virus (IAV) in the following order of potency: SP-D>gp340>SP-A. SP-D binds in a calcium-dependent manner to carbohydrate attachments on the viral hemagglutinin (HA) and neuraminidase (NA). By contrast, gp340 and SP-A act like mucins in that they provide sialic acid ligands that bind to the viral HA. In this study, SP-D, SP-A, and gp340 showed cooperative antiviral interactions. These cooperative effects were most evident in viral aggregation but were also observed in at least some hemagglutination inhibition and viral neutralization assays. The mechanism of binding between gp340 and SP-D was further characterized using monoclonal antibodies. Although gp340 can bind to SP-D at a site distinct from the mannan-binding site, binding of gp340 to SP-D did not contribute to cooperative antiviral interactions. SP-D and mucin showed cooperative interactions, apparently dependent on NA inhibition by SP-D. The commercial NA inhibitor oseltamivir had a similar effect and also enhanced the neutralizing activity of SP-A and bronchoalveolar lavage fluid. Hence, oseltamivir collaborates with innate immune proteins in inhibiting the initial infection of epithelial cells.
Effects of BAY 41–2272, a soluble guanylate cyclase activator, on pulmonary vascular reactivity in the ovine fetus
Authors: Deruelle Philippe , Grover Theresa R. , Storme Laurent , Abman Steven H.
Published: December 2004

Nitric oxide (NO)-cGMP signaling plays a critical role during the transition of the pulmonary circulation at birth. BAY 41–2272 is a novel NO-independent direct stimulator of soluble guanylate cyclase that causes vasodilation in systemic and local circulations. However, the hemodynamic effects of BAY 41–2272 have not been studied in the perinatal pulmonary circulation. We hypothesized that BAY 41–2272 causes potent and sustained fetal pulmonary vasodilation. We performed surgery on 14 fetal lambs (125–130 days gestation; term = 147 days) and placed catheters in the main pulmonary artery, aorta, and left atrium to measure pressures. An ultrasonic flow transducer was placed on the left pulmonary artery (LPA) to measure blood flow, and a catheter was placed in the LPA for drug infusion. Pulmonary vascular resistance (PVR) was calculated as pulmonary artery pressure minus left atrial pressure divided by LPA blood flow. BAY 41–2272 caused dose-related increases in pulmonary blood flow up to threefold above baseline and reduced PVR by 75% ( P < 0.01). Prolonged infusion of BAY 41–2272 caused sustained pulmonary vasodilation throughout the 120-min infusion period. The pulmonary vasodilator effect of BAY 41–2272 was not attenuated by Nω-nitro-l-arginine, a NO synthase inhibitor. In addition, compared with sildenafil, a phosphodiesterase 5 inhibitor, the pulmonary vasodilator response to BAY 41–2272 was more prolonged. We conclude that BAY 41–2272 causes potent and sustained fetal pulmonary vasodilation independent of NO release. We speculate that BAY 41–2272 may have therapeutic potential for pulmonary hypertension associated with failure to circulatory adaptation at birth, especially in the setting of impaired NO production.