S U M M A R Y T h e current status of instrumentation for S P E C T and P E T has been reviewed buy 35mg residronate mastercard treatment plan for depression. In both modes generic 35 mg residronate medications with aspirin, m u c h effort has been m a d e to increase detection sensitivity by 3 - D data acquisition by the use of cone b e a m or m o r e sophisticated 3 - D collimation in S P E C T trusted residronate 35mg treatment 5th metatarsal fracture, or by 3 - D data acquisition in P E T. Howev e r , the fully 3 - D image recon struction and data correction for the attenuation and scatter of photons in the 3 - D m o d e are still in the development stage. Further w o r k is needed o n quantitation issues to reach the goal of septa-less 3 - D P E T. In order to avoid the problems inherent in data reconstruction and back projection in the field of image tomography, a technique for segmentation of the raw projection data set has been developed with the aim of providing quantitative parameters. I N T R O D U C T I O N T h e widespread adoption of single photon emission computed tomography ( S P E C T ) during the 1980s w a s a significant step forward in nuclear medicine. It offered a w a y of obtaining three dimensional information about the distribution of radioactivity in a patient. T o further develop the technique, numerous methods have been described in the literature (for example, Refs [1-4]) that aim to provide quantitative parameters to improve the sensitivity and specificity of the type of study under consideration. H o w ever, all of these methods are affected to varying degrees by several limi tations. S o m e of the important ones a m o n g these are noise, scatter, attenuation, detector response, sampling errors, pharmacokinetic redistribution and radionuclidic decay during acquisition, and the artefacts introduced by the reconstruction algorithm and filtering used . M u c h w o r k has been done to estimate the effects of each of these factors, to provide methods attempting to deal with the inaccuracies caused by t h e m and to assist in quantitation (for example, Refs [6-12]), but none of the approaches are in widespread use. Secondly, no correction is performed for time variance of the activity distri bution due to pharmacokinetics. All of these factors assume even greater importance w h e n there is a large spread of contrast values and the organ of interest is close to other organs with large amounts of activity. This m e a n s that all post-reconstruction techniques for correction, segmentation and quantitation have not as yet achieved wide acceptance due to differing equipment, acquisition protocols and analysis methods between centres, with each centre tailoring its o w n combination to cover a particular set of procedures. A n important consequence is that standardized clinical databases are difficult to develop. Since there is a clinical need for these types of values, a technique that can pro vide the ability to say, simply, ‘x M B q. Such values can be used in a wide variety of ways, including the ability to compare patterns of distribution in tomographic studies performed at different times. This m e a n s that time can be used as an additional factor in deriving quantitative parameters. Besides being required in routine studies, these quantitative data are essential for dosimetry measurements for radionuclide therapy of cancer and other diseases. M A T E R I A L S A N D M E T H O D S Studies were carried out using a standard Jaszczak S P E C T pha n t o m and patient data wer e acquired according to standardized protocols using a Siemens Orbiter g a m m a camera and transferred to Nuclear Diagnostics workstations for analysis. T h e technique described here has been implemented using the X W i n d o w System (trademark of the Massachusetts Institute of Technology) running on a S u n w o r k station (Sun Microsystems, Inc. It m a k e s use of the software library routines ‘N U C L I B ’supplied by Nuclear Diagnostics Ltd. These library routines provide structures to facilitate the input/output, m e m o r y storage and display of nuclear medicine image data. T h e basic premises of this m e thod are that a r a w data set contains all the infor mation necessary to characterize the distribution of radioactivity in three dimensions and that, for a given data set, it is possible to describe the relationships between the entire set of projections as a set of mathematical functions. O n c e this description is made, it is possible to manipulate the data set to predict clinically advantageous ‘what if scenarios that maintain the relationships and provide quantitative parameters. A user defined seed pixel within this object starts off a three dimensional edge detector that produces a series of discrete points defining the boundaries that satisfy a preset target range and edge sharpness, and terminates w h e n all such points have been identified. A least squares fit to this set of edge pixels defines the boundary of the object according to an assumed ellipsoid or irregular shape selected by the user. T h e algorithm then forms an estimate of the outline of the patient’s bod y according to a preset threshold from the limits as seen in all the projections, and also the m e a n background counts free fro m all other major objects. Next, a copy of the delineated object as well as the estimated body outline is produced in a n e w data set to f or m the basis of the forward projection simulation module. T h e pixels within the b o d y out line are given an initial count value based on the estimate of the m e a n background, and the pixels within the object of interest are given an arbitrary initial count value by the user. These counts are then forward projected by a M o n t e Carlo subroutine that isotropically distributes these initial estimates of counts per voxel for each projection angle. This subroutine takes into consideration the aforementioned attenu ation m a p s (and any additional attenuation corrections if required), noise, m o dula tion transfer function and time variance of activity within the segmented organ due to pharmacokinetic redistribution or radionuclidic decay. A chi-squared statistic is calculated to c ompare the simulated data with the actual data based o n the projections with the majority of the counts arising from the object of interest, and used to revise the initial estimates iteratively. This procedure converges to a point w h e n the simula tion mirrors the original data closely for only the delineated object independent of all others. A t this point, the algorithm can branch in one of t w o w a y s by either deleting the segmented object fro m the r a w data set or keeping the object but deleting every thing else, i. This decision is m a d e by the user based o n the clinical situation for which the study w a s performed. T h e quantitative data about the object, namely the volume, activity and time variance during the period of acquisition are inferred f rom the values of these parameters used during the simulation to get the m i n i m u m chi-squared statistic.
Fondaparinux is absolutely contraindicated in those with a creatinine clearance of <30 mL/min and should be used with caution in individuals with a creatinine clearance of <50 mL/min residronate 35mg with mastercard treatment 31st october. The individual presented in scenario B has a creatinine clearance of 32 mL/min and should not receive fondaparinux discount 35 mg residronate treatment for pneumonia. Finally generic residronate 35 mg with visa treatment 4 toilet infection, there have been several case reports of successful use of fondaparinux in the treatment of heparin-induced thrombocytopenia as there is no cross-reactivity be- tween it and heparin-induced thrombocytopenia antibodies. However, the presence of a dominant breast nodule/mass during pregnancy should never be attributed to hor- monal changes. The prognosis for breast cancer by stage is no different in pregnant compared with pregnant women. Nev- ertheless, pregnant women are often diagnosed with more advanced disease because of delay in the diagnosis. Pregnant patients with persistent lumps in the breast should be re- ceive prompt diagnostic evaluation. Acquired aplastic anemia may be due to drugs or chemicals (ex- pected toxicity or idiosyncratic effects), viral infections, immune diseases, paroxysmal noc- turnal hemoglobinuria, pregnancy, or idiopathic causes. Aplastic anemia from idiosyncratic drug reactions (including those listed as well others including as quinacrine, phenytoin, sul- fonamides, cimetidine) are uncommon but may be encountered given the wide usage of some of these agents. In these cases there is usually not a dose-dependent response; the reac- tion is idiosyncratic. Seronegative hepatitis is a cause of aplastic anemia, particularly in young men who recovered from an episode of liver inﬂammation 1–2 months prior. In the absence of drugs or toxins that cause bone marrow suppression, it is most likely that he has immune-mediated injury. Transfusion should be avoided unless emergently needed to prevent the development of alloantibodies. Immunosuppression with antithy- mocyte globulin and cyclosporine is a therapy with proven efﬁcacy for this autoimmune disease with a response rate of up to 70%. Relapses are common and myelodysplastic syn- drome or leukemia may occur in approximately 15% of treated patients. Immunosuppres- sion is the treatment of choice for patients without suitable bone marrow transplant donors. Bone marrow transplantation is the best current therapy for young patients with matched sibling donors. Allogeneic bone marrow transplants from matched siblings result in long term survival in >80% of patients, with better results in children than adults. Adenocarcinomas are strongly associated with thrombosis (Trousseau’s syndrome) and may cause ascites, but hemolysis without mi- croangiopathic hemolytic anemia makes this less likely. Characteristic ﬁndings include a history of exposure to sandﬂies at night or darkening of the skin on physical examination. Miliary tuberculosis is on the differential but would be unlikely with a normal chest radiograph. Cirrhosis of the liver may present this way although the persis- tent fevers would be uncharacteristic. Ingestion of warfarin may also cause this clinical scenario but is less likely given the inheritance pattern. Congenital or nutritional deﬁciencies of these factors will be corrected in the laboratory by the addition of serum from a normal subject. The presence of a spe- ciﬁc antibody to a coagulation factor is termed an acquired inhibitor. Patients with acquired inhibitors are typically older adults (median age 60) with pregnancy or post-partum states being less common. The most common underlying dis- eases are autoimmune diseases, malignancies (lymphoma, prostate cancer), and derma- tologic diseases. Developing the coagulation disorder later in life is more suggestive of an acquired inhibitor if there is no antecedent history of coagulopa- thy. A tobacco history and laboratory evidence of chronic illness (anemia, hypoalbuminemia) in this scenario raise the suspicion of an underlying malignancy. It has a prevalence in the general population of 1:5000 in contrast to Hemophilia B that has a prevalence of 1:30,000. The disease phe- notype correlates with the amount of residual Factor activity and can be classiﬁed as se- vere (<1% activity), moderate (1–5% activity) or mild (6–30% activity). Hemophiliacs have a normal bleeding time, platelet count, thrombin time and prothrombin time. This and the presence of ascites raise the possibility of liver disease and cirrhosis. It is estimated in 2006 that >80% of hemophilia patients >20 years old are infected with hepatitis C virus.
There has been an increasing realisation of the social and cultural situatedness of medicine cheap 35 mg residronate mastercard medications given to newborns, healthcare and knowledge systems: individuals discount residronate 35mg fast delivery treatment tinnitus, groups of individuals and societies at large understand and respond differently to the perennial phenomena of sickness and suffering buy 35 mg residronate with mastercard symptoms jaw pain, health and disease, pain and death; and these reac- tions are reﬂected in different medical ideas, different ‘healthcare systems’, different value systems, each of which has its own social, economic and cultural ramiﬁcations. This appreciation of the variety of healthcare (and knowledge) systems – and indeed of the variety within one system – is no doubt related to the increasing acceptance of ‘alternative’ or ‘comple- mentary’ medicine in the Western world and the corresponding changes in medical practice, doctor–patient relationship and the public perception of the medical profession. And the traditional assumption of a superiority of Western, scientiﬁc medicine over non-Western, ‘primitive’, ‘folklore’ or ‘al- ternative’ medicine has virtually reached the state of political incorrectness. This shift in attitude has had rather paradoxical implications for the study of ancient medicine. In short, one could say that attention has widened from texts to contexts, and from ‘intellectual history’ to the history of ‘dis- courses’ – beliefs, attitudes, perceptions, expectations, practices and rituals, their underlying sets of norms and values, and their social and cultural ramiﬁcations. At the same time, the need to perceive continuity between 4 For a more extended discussion of this development see the Introduction to Horstmanshoff and Stol (2004). Introduction 5 Greek medicine and our contemporary biomedical paradigm has given way to a more historicising approach that primarily seeks to understand med- ical ideas and practices as products of culture during a particular period in time and place. As a result, there has been a greater appreciation of the diversity of Greek medicine, even within what used to be perceived as ‘Hippocratic medicine’. For example, when it comes to the alleged ‘ratio- nality’ of Greek medicine and its attitude to the supernatural, there has ﬁrst of all been a greater awareness of the fact that much more went on in Greece under the aegis of ‘healing’ than just the elite intellectualist writing of doctors such as Hippocrates, Diocles and Galen. Thus, as I argue in chapter 1 of this volume, the author of On the Sacred Disease, in his criticism of magic, focuses on a rather narrowly deﬁned group rather than on religious healing as such, and his insistence on what he regards as a truly pious way of approaching the gods suggests that he does not intend to do away with any divine intervention; and the author of the Hippocratic work On Regimen even positively advocates prayer to speciﬁc gods in combination with dietetic measures for the prevention of disease. Questions have further been asked about the historical context and representativeness of the Hippocratic Oath and about the extent to which Hippocratic deontology was driven by considerations of status and reputa- tion rather than moral integrity. And the belief in the superiority of Greek medicine, its perceived greater relevance to modern medical science – not to mention its perceived greater efﬁcacy – compared with other traditional healthcare systems such as Chinese or Indian medicine, has come under attack. As a result, at many history of medicine departments in universi- ties in Europe and the United States, it is considered naıve¨ and a relic of old-fashioned Hellenocentrism to start a course in the history of medicine with Hippocrates. This change of attitude could, perhaps with some exaggeration, be described in terms of a move from ‘appropriation’ to ‘alienation’. Greek, in particular Hippocratic medicine, is no longer the reassuring mirror in which we can recognise the principles of our own ideas and experiences of health and sickness and the body: it no longer provides the context with which we can identify ourselves. Nevertheless, this alienation has brought about a very interesting, healthy change in approach to Greek and Roman medicine, a change that has made the subject much more interesting and 5 For an example see the case study into experiences of health and disease by ‘ordinary people’ in second- and third-century ce Lydia and Phrygia by Chaniotis (1995). An almost exclusive focus on medical ideas and theories has given way to a consideration of the relation between medical ‘science’ and its environment – be it social, political, economic, or cultural and religious. Indeed ‘science’ itself is now understood as just one of a variety of human cultural expressions, and the distinction between ‘science’ and ‘pseudo-science’ has been abandoned as historically unfruitful. And medicine – or ‘healing’, or ‘attitudes and ac- tions with regard to health and sickness’, or whatever name one prefers in order to deﬁne the subject – is no longer regarded as the intellectual property of a small elite of Greek doctors and scientists. There is now a much wider deﬁnition of what ‘ancient medicine’ actually involves, partly inspired by the social and cultural history of medicine, the study of medical anthropology and the study of healthcare systems in a variety of cultures and societies. The focus of medical history is on the question of how a soci- ety and its individuals respond to pathological phenomena such as disease, pain, death, how it ‘constructs’ these phenomena and how it contextualises them, what it recognises as pathological in the ﬁrst place, what it labels as a disease or aberration, as an epidemic disease, as mental illness, and so on. How do such responses translate in social, cultural and institutional terms: how is a ‘healthcare system’ organised? How do they communicate these to their colleagues and wider audiences, and what rhetorical and argumentative techniques do they use in order to persuade their colleagues and their customers of the preferability of their own approach as opposed to that of their rivals? How is authority established and maintained, and how are claims to competence justiﬁed? The answers to these questions tell us something about the wider system of moral, social and cultural values of a society, and as such they are of interest also to those whose motivation to engage in the subject is not primarily medical. As the comparative history of medicine and science has shown, societies react to these phenomena in different ways, and it is interesting and illuminating to compare similarities and differences in these reactions, since they often reﬂect deeper differences in social and cultural values. Introduction 7 and public hygiene and healthcare, and how they coped – physically as well as spiritually – with pain, illness and death. In this light, the emergence of Greek ‘rational’ medicine, as exempliﬁed in the works of Hippocrates, Galen, Aristotle, Diocles, Herophilus, Erasistratus and others, was one among a variety of reactions and responses to disease. Of course, this is not to deny that the historical signiﬁcance of this response has been tremendous, for it exercised great inﬂuence on Roman healthcare, on medieval and early modern medicine right through to the late nineteenth century, and it is arguably one of the most impressive contributions of classical antiquity to the development of Western medical and scientiﬁc thought and practice. But to understand how it arose, one has to relate it to the wider cultural environment of which it was part; and one has to consider to what extent it in turn inﬂuenced perceptions and reactions to disease in wider layers of society. The medical history of the ancient world comprises the role of disease and healing in the day-to-day life of ordinary people. It covers the relations between patients and doctors and their mutual expectations, the variety of health-suppliers in the ‘medical marketplace’, the social position of healers and their professional upbringing, and the ethical standards they were required to live up to. It is almost by deﬁnition an interdisciplinary ﬁeld, involving linguists and literary scholars, ancient historians, archaeologists and envi- ronmental historians, philosophers and historians of science and ideas, but also historians of religion, medical anthropologists and social scientists. Thus, as we shall see in the next pages, medical ideas and medical texts have enjoyed a surge of interest from students in ancient philosophy and in the ﬁeld of Greek and Latin linguistics. Likewise, the social and cultural history of ancient medicine, and the interface between medicine, magic 7 See, e. Indeed, my own inter- ests in ancient medicine were ﬁrst raised when I was studying Aristotle’s Parva naturalia and came to realise that our understanding of his treat- ment of phenomena such as sleep, dreams, memory and respiration can be signiﬁcantly enhanced when placing it against the background of medical literature of the ﬁfth and fourth centuries.