This would seem profoundly objectionable from the point of view of justice gastritis diet vegetable recipes order cheap gasex, and likely would have a negative impact on the psychosocial identity formation of people with those characteristics gastritis diet questionnaire proven gasex 100caps. The argument was originally made in relation to prenatal screening gastritis duodenitis generic gasex 100caps visa, but would have similar force in relation to genome editing gastritis diet salad purchase gasex 100caps with visa. This is not the case gastritis diet livestrong buy gasex 100caps with amex, however gastritis diet food list order gasex without a prescription, with the inherited genetic disorders that are the most likely targets for genome editing gastritis diet natural treatment discount gasex 100 caps without prescription, which manifest in ways that significantly affect quality and length of life gastritis and bloating generic 100 caps gasex with visa. It does, nevertheless, highlight the need to take into account the interests of those who are placed in positions of increased vulnerability as a result of the introduction of new technologies. A human rights-based approach is helpful in drawing attention to these considerations, but its utility is limited if it is only deployed defending against the negative consequences of particular proposed innovations. Complementary to this, there is a need for reflection and action on broader questions that give consideration to the sort of society to which innovation decisions collectively give rise. We discuss this kind of broader reflection below, and in Chapter 4 we propose how it might be better supported. One way to understand this idea is that the experience of fragility can give rise to other things of value, such as care, compassion and generosity. Drawing analogies with other cases in which care is valued, bioethics scholar Erik Parens observes that many would object to the idea that we should use genetic technology to end, for instance, adolescence or old age and their associated challenges. He argues that we should treat the fragility associated with some genetic characteristics in the same way. Moral philosopher Mike Parker considers instead the place of fragility in the life of an individual, rather than of individuals in society or the human race as a whole, and argues that human flourishing comprises aspects of both strength and weakness. To attempt to eradicate negative elements of human experience in this sense would be counterproductive. It seems difficult to make a strong case that any particular genetic characteristic should be maintained at least unless that characteristic were in some way one that was essential to what it is to be human (though this seems unlikely). Some argue that selective reproductive technologies communicate something about the lesser status or value ascribed to disabled people by society, which can not only cause psychological damage, but can also give rise to wider harms through the effects on broader social attitudes towards disabled people. A common objection is that any negative message that might be communicated by these uses of reproductive technology need not be about disabled individuals themselves; it is possible to disvalue a condition that gives rise to disability at the same time as valuing people who have the condition as highly as those who do not. Whether or not it is warranted to regard selective reproductive technologies as necessarily conveying any message, their availability might nevertheless distress or offend some disabled people. Empirical work in this area has found that some disabled people do find the availability of reproductive technology to select against disabled babies distressing, devaluing or offensive. Restrictive measures are in any case unlikely to be necessary to preserve fragility either at the social level (Parens) or at the individual level (Parker). Sociologist Tom Shakespeare dismisses predictions of an end to disability by observing that instances of disability will always arise. Even when norms shift, the idea that this distinction can be made remains constant. It is possible, however, that people or their morally considerable interests will find themselves in a different relationship to the norm as the use of new technologies diffuses. As we argued in Chapter 2, although shifting social norms are not necessarily a bad thing in themselves, they can affect the distribution of advantages and disadvantages among people. Even if all benefit, there may be concerns if some benefit substantially more than others. But certain goods are more fundamental to leading a fulfilling life, and for this reason are often the sort on which the protections of human rights have traction. Though significantly different and more complex than basic healthcare, we have suggested above that the opportunity to have genetically related offspring is a good that is widely regarded in this way. Doing so can help to illuminate concerns about distributional effects and the potential for unintended consequences. We suggested a possible starting point for these deliberations in Chapter 2 when we considered how the use of genome editing might grow beyond the rare cases of first use, migrating to other indications as conditions permitted. In the present chapter, we have started to think about the social implications of possible technological innovations and of decisions to apply them in individual cases. The further step is to imagine what it might be like to live in such a world as differently embodied inhabitants and how different socio-technical conditions would affect the fulfilment or frustration of interests. What we propose is more modest; namely, to examine and juxtapose the different ways of valuing that those who have different interests in the matter bring to it. This can be achieved by engaging with the views of those whose interests are affected by heritable genome editing interventions, expressed in their own terms and understood against the background of their own values and experiences. Since a shift in norms can engage the interests of those who hitherto might consider themselves to be disinterested observers and to the extent that these normative developments re-pattern the moral fabric of society, this is potentially everyone. In Chapter 4, we make recommendations to facilitate this kind of engagement and thereby to help to ensure that the social justice and solidarity principle is addressed. A virtue of this sort of approach is to be able to attend to voices that may be obscured in the outcomes of decision-focused debates and particularly in aggregative procedures. On this, see: Nuffield Council on Bioethics (2012) Emerging biotechnologies: technology, choice and the public good, available at: nuffieldbioethics. We found that there is a strong moral claim to be allowed to pursue this interest without interference and that may, in some cases, enjoin positive assistance. However, we noted that there were limits: not all uses of genome editing to improve the welfare of future people were acceptable. We had to consider the wider implications, including the indirect effects on others and conformity with the system of moral norms that implicitly underpin the moral community. We found that if heritable genome editing interventions are to be introduced, it will be important to do so in a way that does not increase unfairness and disadvantage. We recognise the danger of consideration of the full range of relevant interests being obscured or distorted by a focus on the immediate goals of prospective parents, perhaps because others are less directly affected, perhaps only after a considerable time and perhaps, albeit in greater numbers, to a lesser extent individually. Certain consultative or democratic procedures, particularly those that are focused on a binary choice constructed around a particular solution. This works against the possibility of constructive engagement between more complex and nuanced positions and of discovering circumstances that can support consensus. Particular efforts are therefore needed to engage in open and 298 the cases in which support is enjoined will depend partly on the technological pathways available and would depend partly on the social context (whether funding is available and equitable provision is possible, etc. Some would consider it a benefit to be able to spare their descendants from the likelihood of an undesired characteristic resurfacing in each new generation. Others would see this as an arrogant constraint on their freedom, an attempt to fit them for a particular kind of life that they may not want. The potential for transmission of changes through many generations compounds concerns about safety. It introduces the worry that potential adverse effects might incubate without manifesting for long periods, only becoming evident late in life or even after several generations, by which point they might have diffused to multiple descendants. There are rare reversion mutations, recombination events and even interacting/compensating/complementing mutations that may affect the transmission of the specific alteration through generations of cells and people. Except where the effect is analogous to that of a single gene disorder, it would be difficult to isolate the impact of an introduced variant as the cause of an observed harm (or, therefore, as being the automatic target for further remedial intervention). Haemophilia is known to have passed into a number of European royal families in the nineteenth and twentieth centuries through descendants of Queen Victoria. In many cases, the burden of disease can have a negative and compounding effect on the economic and social circumstances of affected families. It is impossible to assign likelihood to such speculative outcomes in the abstract, but it may also be beside the point: we can try instead to identify the requirements and limits of our responsibilities to future generations. Just as we did in relation to first-generation descendants in the first part of the present chapter, we confront again the problem of finding a way for the interests of those who do not yet exist to figure in our moral reasoning about the circumstances of their existence, although now in a much more attenuated way. It has been particularly prominent in recent decades in public and academic discourse on subjects ranging from developments in nuclear power to (especially) environmental degradation and global climate change. The natural environment comprises distinguishable ecosystems regulated by processes that do not involve substantial human intervention, as well as relatively unbounded resources such as air and water. It is distinguished from conditions that have been fundamentally transformed by and are regulated by human activity. Ecosystems within the natural environment may be highly integrated (with high interdependency between elements) and dynamically stable over time. Climate change, for example, will undoubtedly make significant parts of the earth much less hospitable to humans. Such a project would be reckless at present, given the enormous uncertainties implied in attempting to direct evolution at the molecular level. Thankfully, genome editing is not the only solution, although none of the currently identified solutions is easy or certain. Accordingly, the principle would at least seem to mandate further research and adduced. The Stratigraphy Commission of the Geological Society of London has been considering a proposal to make the Anthropocene a formal division of geological time since 2008. Such a scenario is developed by speculative fiction author and futurologist, Neal Stephenson (Stephenson N (2015) Seven eves (London: Harper Collins Publishers). It is trenchantly stated in a passage from the Brundtland report; see: Brundtland G, Khalid M, Agnelli S, et al. As a matter of policy, this could be a rational response if there is a good reason to expect that future technology will come to the rescue; the difficulty with such a policy is the fundamental inductive uncertainty of technological development. At the end of the second part of the chapter, we concluded that such interventions would be wrong insofar as they produced injustice, but our conclusion was not categorical; we did not say that the interventions were wrong in principle. The arguments we discussed were focused on heritable genome editing interventions at the individual and social levels. We began this chapter with the question of why we should recognise a value attached to enabling people to have the children they want. We have suggested, for the sake of argument, that genome editing could contribute to the salvation of the human species or perhaps lead to it being superseded. The reason for doing so is to illuminate a further question: why should we attach a value to the survival of the human species at allfi The discussion of this question will bring us, finally, to the question of whether there is anything about genetic modifications per se, or certain classes of genetic modification, that mean they should be categorically prohibited because they offend against something of fundamental significance for the nature of human being itself. Many scholars and some existing legal instruments may be taken to imply that either or both of these forms of interference would be (or might be) regarded as morally impermissible. This underlines the value of genetic variation for population resilience (see Chapter 1 above). While it is clear that some combinations of characteristics are biologically prohibited because they could not coexist in the organism. It would seem unreasonable, particularly given changing environmental conditions and evolutionary pressures, to imagine that the variations observed in existing or extinct populations represent the final range of possible, properly human genomic states. This is because of the relative poverty of current knowledge and the fact that we do know that evolution is costly (in terms of false trails), which could translate into a real human cost, and we probably do not know, at present, how to do better by rational design. Such an objection applies much less convincingly, however, to the case in which a given variation is altered to a well- characterised wild-type variation found in a near genetic relative. However, if we were not willing to accept this as an objection in relation to individuals, as we were not when we discussed it in the first part of the present chapter, it seems that we have no better reason to accept it in relation to the future of the species. In the second part of the present chapter, we considered the possibility that aggregate individual choices could lead to a change in social norms connected with a change in the composition of the human population. We noted how this happens through reproductive partner choices and potentially also by epigenetic modifications. Disagreement exists over whether there is any single idea at work in the different discourses in which human dignity is invoked. In philosophical contexts, human dignity is often appealed to by theorists aiming to articulate what is special or distinctive about human beings. It is taken to be a feature possessed by humans but not other animals, one that grounds the unique value and (moral) status of human beings. As such, questions about human dignity relate in important ways to questions about personhood, autonomy, rationality, morality and other concepts associated with normative notions of humanity. Nevertheless, it has been argued that there is no single, coherent concept of human dignity. Such a being might stand in relation to the present era of human beings in much the same relation as human beings now stand to non-human animals. Human dignity has been used as a justification of diametrically opposed policies; for example, both to justify a ban on human embryonic stem research (Germany) and to permit it (Israel). This does not stop it providing a helpful focus for exploring these differences in international debates. The Beyleveld and Brownsword account aims to circumvent this challenge by adopting an extended conception of autonomy that is able to capture borderline cases (Beyleveld D and Brownsword R (2001) Human dignity in bioethics and biolaw (Oxford: Oxford University Press)). Fukuyama did not believe, however, that all people will be deterred from using genetic technologies by the safety risks and thought that, therefore, eugenic projects might emerge. An empirical obstacle is the likelihood that uncontrolled population growth would swamp the outcome of any possible eugenic project. Whereas the possession of a common genome offers certain opportunities for solidarity and altruism and a way in which we can identify with and help others, it is not the reason why we should do so. Although requiring a degree of technical accomplishment that may or may not be possible at some time in the future, their present value is not as predictions, but as thought experiments to help orientate our reflections on what is important about the prospects of genome editing. From this we conclude that what is important is not the conservation or alteration of a particular range of characteristics at the level of the genome, but rather the potential consequences of genomic interventions for people and the social relations in which they stand to one another. These are expressed not in the pursuit of uncertain outcomes, but in the orientation towards those futures. We have concluded that although particular interventions engage and may violate human rights, they do not threaten the basis of human rights as such. We found that although they did not have a stand-alone positive right to assistance from others in this project, their interest was recognised as giving rise to moral claims of considerable force. Because of the peculiar nature of reproduction, whereby an intervention provided to one person has its primary effect on another (namely, a future person yet to be born), we examined the impact of heritable genome editing interventions with particular regard to how they might affect the identity and interests of the future person. We concluded that genome editing of gametes or embryos (or their precursors) would be morally permissible only when compatible with the welfare of a future person who may be born as a result. This includes cases in which there is an unacceptable risk of adverse effects of the procedure itself, and also where the selection is of the kind that might give the future person reasonable grounds to reprove their parents. We emphasise again that in the current state of knowledge, there are few complex characteristics that could be reliably secured by heritable genome editing interventions. For this reason, while concerns about the safety of the procedure may be overcome, it is hard to foresee acceptable uses of heritable genome editing interventions other than as an alternative to existing procedures for the avoidance of heritable genetic disease or for the modification of alleles predisposing to disease risk. It is recognised (as we observed in Chapter 2) that social norms do not remain constant and may be expected to change in relation to technological developments. Such changes should, however, come about in the context of broad societal debate that allows differences of values and interests to surface and to weigh. In the next chapter, we will consider in more detail the role that can be played by governance measures, including legal and regulatory measures, in 339 On the coherence of this concept and its usefulness in governance, see Chapter 1 above and Chapter 4 below.
In the 30 patients reported in the interim analysis of Study 6793 gastritis diet questionnaire purchase gasex 100 caps without a prescription, the mean age was 30 gastritis symptoms when pregnancy order gasex 100 caps on-line. Twenty five of the patients were Caucasian gastritis diet шарики generic gasex 100 caps, three were Asian gastritis diet ppt discount 100caps gasex otc, and one each of Moroccan and Indian ancestry gastritis pylori symptoms generic 100 caps gasex otc. Page 9 of 26 the primary efficacy endpoint of all three studies was the achievement of a sperm density fi 1 gastritis diet холодное gasex 100 caps lowest price. Eight pregnancies continued to term gastritis symptoms acute buy 100caps gasex visa, and 8 healthy babies were born to 7 couples as a result of those studies gastritis lower back pain purchase gasex 100 caps. Before treatment with Gonal-f is instituted, a thorough gynecologic and endocrinologic evaluation must be performed. Patients with tubal obstruction should receive Gonal-f only if enrolled in an in vitro fertilization program. Primary ovarian failure should be excluded by the determination of gonadotropin levels. Patients in later reproductive life have a greater predisposition to endometrial carcinoma as well as a higher incidence of anovulatory disorders. A thorough diagnostic evaluation should always be performed in patients who demonstrate abnormal uterine bleeding or other signs of endometrial abnormalities before starting Gonal-f therapy. Page 11 of 26 Men: Gonal-f (follitropin alfa for injection) is indicated for the induction of spermatogenesis in men with primary and secondary hypogonadotropic hypogonadism in whom the cause of infertility is not due to primary testicular failure. Before treatment with Gonal-f is instituted for azoospermia, a thorough medical and endocrinologic evaluation must be performed. Hypogonadotropic hypogonadism should be confirmed, and primary testicular failure should be excluded by the determination of gonadotropin levels. Prior to Gonal-f therapy for azoospermia in patients with hypogonadotropic hypogonadism, serum testosterone levels should be normalized. Gonadotropin therapy requires a certain time commitment by physicians and supportive Page 12 of 26 health professionals, and requires the availability of appropriate monitoring facilities (see "Precautions/Laboratory Tests"). Safe and effective use of Gonal-f in women requires monitoring of ovarian response with serum estradiol and vaginal ultrasound on a regular basis. Careful monitoring of ovarian response can further minimize the risk of overstimulation. It is characterized by an apparent dramatic increase in vascular permeability which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events (see "Pulmonary and Vascular Complications"). A physician experienced in the management of this syndrome, or who is experienced in the management of fluid and electrolyte imbalances should be consulted. In addition, thromboembolic events both in association with, and separate from Ovarian Hyperstimulation Syndrome have been reported with gonadotropins including Gonal-f. Intravascular thrombosis and embolism can result in reduced blood flow to critical organs or the extremities. Sequelae of such events have included venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb. In rare cases, pulmonary complications and/or thromboembolic events have resulted in death. Multiple Births: Reports of multiple births have been associated with Gonal-f treatment. The patient should be advised of the potential risk of multiple births before starting treatment. Page 14 of 26 Information for Patients: Prior to therapy with Gonal-f, patients should be informed of the duration of treatment and monitoring of their condition that will be required. Laboratory Tests: In most instances, treatment of women with Gonal-f results only in follicular recruitment and development. This may be estimated by ultrasound alone or in combination with measurement of serum estradiol levels. The combination of both ultrasound and serum estradiol measurement are useful for monitoring the development of follicles, for timing of the ovulatory trigger, as well as for detecting ovarian enlargement and minimizing the risk of the Ovarian Hyperstimulation Syndrome and multiple gestation. It is recommended that the number of growing follicles be confirmed using ultrasonography because plasma estrogens do not give an indication of the size or number of follicles. The clinical confirmation of ovulation, with the exception of pregnancy, is obtained by direct and indirect indices of progesterone production. When used in conjunction with the indices of progesterone production, sonographic visualization of the ovaries will assist in determining if ovulation has occurred. Page 15 of 26 Accurate interpretation of the indices of follicle development and maturation require a physician who is experienced in the interpretation of these tests. Carcinogenesis, Mutagenesis, Impairment of Fertility: Long- term studies in animals have not been performed to evaluate the carcinogenic potential of Gonal-f. However, follitropin alfa showed no mutagenic activity in a series of tests performed to evaluate its potential genetic toxicity including, bacterial and mammalian cell mutation tests, a chromosomal aberration test and a micronucleus test. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the nursing infant from Gonal-f, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Adverse events occurring in more than 10% of patients were headache, ovarian cyst, nausea, and upper respiratory tract infection in the U. Adverse events (without regard to causality assessment) occurring in at least 2% of patients are listed in Table 13 and Table 14. The safety profiles from these two studies were comparable to that of the data presented above. Overall, both presentations were well tolerated and local tolerability between the two groups was comparable. Injection site inspections revealed very rare local reactions (mild redness in one patient after single-dose injection and mild bruising in two subjects after multi-dose injection). Subjective assessments indicated minimal or mild transient pain in two and five subjects who received Gonal-f single-dose and Gonal-f multi-dose, respectively. Page 19 of 26 the following medical events have been reported subsequent to pregnancies resulting from gonadotropins in controlled clinical studies: 1. The following adverse reactions have been previously reported during menotropin therapy: 1. Hemoperitoneum There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have undergone multiple drug regimens for ovulation induction; however, a causal relationship has not been established. Men: the safety of Gonal-f was examined in 3 clinical studies that enrolled 72 patients for induction of spermatogenesis and fertility of whom 56 patients received Gonal-f. One hundred and twenty-three adverse events, including 7 serious events, were reported in 34 of the 56 patients during Gonal-f treatment. Page 20 of 26 In Study 5844, 21 adverse events, including 4 serious adverse events, were reported by 14 of the 26 patients (53. Events occurring in more than one patient were varicocele (4) and injection site reactions (4). The 4 serious adverse events were testicular surgery for cryptorchidism, which existed prestudy, hemoptysis, an infected pilonidal cyst, and lymphadenopathy associated with an Epstein-Barr viral infection. In Study 6410, 3 adverse events were reported in 2 of the 8 patients (24%) treated with Gonal-f. One serious adverse event was reported, surgery for gynecomastia which existed at baseline. The most common events of possible, probable, or definite relationship to study drug therapy occurring in more than 2 patients were: acne (25 events in 13 patients; 59% of patients); breast pain (4 events in 3 patients; 13. Two serious adverse events (hospitalization for drug abuse and depression) were reported by a single patient in the interim analysis. A total of 12,026 injections of Gonal-f were administered by the 56 patients who received Gonal-f in Studies 5844, 6410, and 6793 combined. The injections were well- tolerated, with no or mild reactions (redness, swelling, bruising and itching) reported by patients for 93. Postmarketing Experience In addition to adverse events reported from clinical trials, the following events have been reported during postmarketing use of Gonal-f. Because these reactions were reported voluntarily from a population of uncertain size, the frequency or a causal relationship to Gonal-f, can not be reliably determined. Dosage: Infertile Patients with oligo-anovulation: the dose of Gonal-f (follitropin alfa for injection) to stimulate development of the follicle must be individualized for each patient. Gonal-f should be administered until adequate follicular development is indicated by serum estradiol and vaginal ultrasonography. Further dose increases of the same magnitude could be made, if necessary, every seven days. Treatment duration should not exceed 35 days unless an E2 rise indicates imminent follicular development. Chorionic gonadotropin should be withheld if the serum estradiol is greater than 2,000 pg/mL. The initial dose administered in the subsequent cycles should be individualized for each patient based on her response in the preceding cycle. The precautions described above should be followed to minimize the chance of development of the Ovarian Hyperstimulation Syndrome. In light of the indices and parameters mentioned, it should become obvious that, unless a physician is willing to devote considerable time to these patients and be familiar with and conduct the necessary laboratory studies, he/she should not use Gonal-f. Assisted Reproductive Technologies: As in the treatment of patients with oligo- anovulatory infertility, the dose of Gonal-f to stimulate development of the follicle must be individualized for each patient. Treatment should be continued until adequate follicular development is indicated as determined by ultrasound in combination with measurement of serum estradiol levels. Page 23 of 26 Male Patients with Hypogonadotropic Hypogonadism: the dose of Gonal-f (follitropin alfa for injection) to induce spermatogenesis must be individualized for each patient. Treatment should continue for a period sufficient to achieve serum testosterone levels within the normal range. Gonal-f may need to be administered for up to 18 months to achieve adequate spermatogenesis. The doctor, nurse, or pharmacist should show the patient how to locate the syringe marking that corresponds to the prescribed dose. Page 24 of 26 Patient Instructions for Use for Gonal-f Multi-Dose Vial Step 1: Mixing (reconstituting) Gonal-f Multi-Dose Vial 1. Position the needle of the syringe of water in a straight, upright position over the marked center circle of the rubber stopper on the vial of Gonal-f Multi-Dose powder. Keep the needle in a straight, upright position as you insert it through the center circle, or it may be difficult to depress the plunger. When all the water has been injected into the vial, withdraw the needle and safely dispose of it immediately in your needle container. Wipe the rubber stopper of the vial of Gonal-f Multi-Dose liquid with an alcohol wipe. Firmly hold the vial of Gonal-f Multi-Dose liquid on a flat surface, insert the needle through the marked center circle of the rubber stopper. Keeping the needle in the vial, lift the vial and turn it upside down with the needle pointing toward the ceiling. With the needle tip in the liquid, slowly pull back the plunger until the syringe fills to slightly more than the mark for your prescribed dose. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. For marketed products discussed in this presentation, please see full prescribing information on our website Nuclear medicine practitioners that receive radiopharmaceuticals that originate from sources other than the manufacturers listed in these tables may be using unapproved copies. Among these patients, it may be used to help identify patients with lower one and two year mortality risks, as indicated by an H/M ratio fi 1. Limitations of Use: In patients with congestive heart failure, its utility has not been established for: selecting a therapeutic intervention or for monitoring the response to therapy; using the H/M ratio to identify a patient with a high risk for death. It is intended for informational purposes only and is not intended to promote or recommend any individual product. Contact the applicable manufacturer if you have any questions regarding a product listed on this document. Alkek Distinguished Chair of Medicine Baylor College of Medicine Houston, Texas Kathleen A. Duncan Professor Chief, Section of Hematology/Oncology Associate Director for Clinical Research Dan L. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher. Research and clinical experience are continually expanding our knowledge, in particular our under- standing of proper treatment and drug therapy. The authors, editors, and publisher have made every effort to ensure that all information in this book is in accordance with the state of knowledge at the time of production of the book. Nevertheless, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the contents of the publication. Every reader should examine carefully the package inserts accompanying each drug and should carefully check whether the dosage schedules mentioned therein or the contraindications stated by the manufacturer differ from the statements made in this book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market. Library of Congress Cataloging-in-Publication Data Tumor board review: guideline and case reviews in oncology / editors, Robert F. Primary Brain Tumors 278 Daniel Da Graca, Mariela Blum, Abhishek Marballi, Janet Wang, and Pamela New Garrett R. Acute Lymphoblastic Leukemia 348 Sumana Devata, John Magenau, and Dale Bixby Musa Yilmaz and Mark M. Acute Myelogenous Leukemia 357 Answers 405 Kavitha Beedupalli and Gustavo Rivero Index 411 30. The editors gratefully acknowledge the the most recent advances in diagnosis and treatment that contributions of our trainee and faculty authors, as well have emerged from recently published clinical trials. Most as the support staff who assisted in the preparation of prominent among the diagnostic advances is the further each chapter. We also thank the editorial staff of Demos identification of genetic mutations that point to selective Medical Publishing, particularly Richard Winters, execu- anticancer drug sensitivity. As trainees, we are oncology subspecialty trainees and practitioners who are urged to learn as much as we can from each patient who preparing for subspecialty certification or recertification, provides a case-specific context for applying the broader respectively; trainees at all levels. In the academic practice of oncol- readable, case-based review of the relevant oncology lit- ogy, we encourage our trainees to attend tumor boards, erature; and oncologists in practice who are looking for a which, by applying the knowledge and expertise of rel- concise opportunity to refresh their knowledge across the evant oncology specialists to the problems of individual broad field of medical oncology. The tumor board as a venue for learning possible by the combined efforts of selected subspecialty was the concept we applied to the design of Tumor Board fellows and expert faculty of two academic institutions, Review: Guideline and Case Reviews in Oncology. Each the Baylor College of Medicine (Houston, Texas) and of the 32 chapters follows a uniform format: a concise the University of Michigan Medical School (Ann Arbor, summary of the epidemiology, risk factors, natural his- Michigan). The editors gratefully acknowledge the dedi- tory, and pathology of each major organ-specific tumor cated participation of our trainee and faculty authors, type; an abbreviated display of the relevant staging (gener- and the support staff of both academic centers, the latter ally based on the American Joint Commission on Cancer including the invaluable editorial support of Ms. Clearly, it was our intention to make the case summaries and accompanying evidence- Robert F. Positive margins necessitate re-excision Society estimated that about 55,000 Americans were diag- or radiation treatment in most cases. Of these, tobacco exposure and Patients with locally advanced, curable disease are alcohol consumption are the 2 main causes, and when treated with surgery followed by radiation with or without combined, they increase the risk by about 100-fold com- chemotherapy, or with definitive chemoradiation. This may reflect a difference in treatment is based on the primary site of origin (see Table tumor biology or simply more favorable host factors such 1. For example, oral cavity tumors are treated primar- as younger age and fewer comorbidities (and therefore ily with surgery because advances in reconstruction using better tolerance of treatments). The multimodality approach allows cure even and hypopharynx cancers can be treated either with organ in locally advanced, unresectable cancers. Furthermore, preservation approaches or total laryngectomy followed organ preservation is achievable in a considerable number by radiation with or without chemotherapy. Incurable disease Hypopharynx Postcricoid area, pyriform sinuses implies the presence of distant metastases. His neck mass remained mary care physician 3 months after noticing a small, pea- stable until 5 months after his initial presentation when it sized right neck mass that subsequently started to grow. He sought medical care after developing Treatment with antibiotics and steroids brought initial, dysarthria, difficulty chewing, and a sensation of airway short-lived relief, but then the neck mass further increased narrowing. He had a 60-pack-year smoking 4 Tumor Board Review history and a history of excessive alcohol consumption.
Staging is based on the determination of the anatomic extent of disease and assessment of serum tumour markers gastritis hiv symptom discount gasex 100caps overnight delivery. The following are the procedures for assessing N acute gastritis symptoms treatment order 100caps gasex with mastercard, M gastritis blog order gasex in india, and S categories: N categories Physical examination and imaging M categories Physical examination gastritis treatment probiotics generic 100caps gasex mastercard, imaging gastritis diet soy milk gasex 100caps amex, and biochemical tests S categories Serum tumour markers Stages are subdivided based on the presence and degree of elevation of serum tumour markers gastritis nsaids buy 100caps gasex amex. Regional Lymph Nodes the regional lymph nodes are the abdominal para aortic (periaortic) gastritis green tea generic 100caps gasex free shipping, preaortic gastritis symptoms pain in back 100caps gasex free shipping, interaortocaval, precaval, paracaval, retrocaval, and retroaortic nodes. The intrapelvic nodes and the inguinal nodes are considered regional after scrotal or inguinal surgery. The following are the procedures for assessing T, N, and M categories: T categories Physical examination, imaging, and endoscopy N categories Physical examination and imaging M categories Physical examination and imaging Anatomical Sites 1. Ureter (C66) Regional Lymph Nodes the regional lymph nodes are the hilar, abdominal para aortic, and paracaval nodes and, for ureter, intrapelvic nodes. The following are the procedures for assessing T, N, and M categories: T categories Physical examination, imaging, and endoscopy N categories Physical examination and imaging M categories Physical examination and imaging Regional Lymph Nodes the regional lymph nodes are the nodes of the true pelvis, which essentially are the pelvic nodes below the bifurcation of the common iliac arteries. The suffix (is) may be added to any T to indicate presence of associated carcinoma in situ. The following are the procedures for assessing T, N, and M categories: T categories Physical examination, imaging, and endoscopy N categories Physical examination and imaging M categories Physical examination and imaging Regional Lymph Nodes the regional lymph nodes are the inguinal and the pelvic nodes. The following are the procedures for assessing T, N, and M categories: T categories Physical examination and imaging N categories Physical examination and imaging M categories Physical examination and imaging Regional Lymph Nodes the regional lymph nodes are the hilar, abdominal para aortic, and paracaval nodes. Ophthalmic Tumours Introductory Notes Tumours of the eye and its adnexa are a disparate group including carcinoma, melanoma, sarcomas, and retinoblastoma. The following are the procedures for assessing T, N, and M categories: T categories Physical examination N categories Physical examination M categories Physical examination and imaging Regional Lymph Nodes the regional lymph nodes are the preauricular, submandibular and cervical lymph nodes. The following are the procedures for assessing T, N, and M categories: T categories Physical examination N categories Physical examination M categories Physical examination and imaging Regional Lymph Nodes the regional lymph nodes are the preauricular, submandibular, and cervical lymph nodes. The following are the procedures for assessing T, N, and M categories: T Physical examination; additional methods such as fluorescein angiography categories and isotope examination may enhance the accuracy of appraisal N Physical examination categories M Examination and imaging categories Regional Lymph Nodes the regional lymph nodes are the preauricular, submandibular, and cervical nodes. If less than half of the tumour volume is located within the iris, the tumour may have originated in the ciliary body and consideration should be given to classifying it accordingly. Ciliary Body and Choroid Primary ciliary body and choroidal melanomas are classified according to the four tumour a, b size categories listed in this section. Figure 1 Classification for ciliary body and choroid uveal melanoma based on thickness and diameter. T1 Tumour size category 1 T1a without ciliary body involvement and extraocular extension T1b with ciliary body involvement T1c without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter T1d with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter T2 Tumour size category 2 T2a without ciliary body involvement and extraocular extension T2b with ciliary body involvement T2c without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter T2d with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter T3 Tumour size category 3 T3a without ciliary body involvement and extraocular extension T3b with ciliary body involvement T3c without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter T3d with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter T4 Tumour size category 4 T4a without ciliary body involvement and extraocular extension T4b with ciliary body involvement T4c without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter T4d with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter T4e Any tumour size category with extraocular extension more than 5 mm in diameter Notes a In clinical practice, the largest tumour basal diameter may be estimated in optic disc diameters (dd, average: 1 dd = 1. However, techniques such as ultrasonography and fundus photography are used to provide more accurate measurements. Ciliary body involvement can be evaluated by the slit lamp, ophthalmoscopy, gonioscopy, and transillumination. However, high frequency ultrasonography (ultrasound biomicroscopy) is used for more accurate assessment. Extension through the sclera is evaluated visually before and during surgery, and with ultrasonography, computed tomography, or magnetic resonance imaging. Retinoblastoma Rules for Classification In bilateral cases, the eyes should be classified separately. The classification does not apply to complete spontaneous regression of the tumour. The following are the procedures for assessing T, N, and M categories: T Physical examination and imaging categories N Physical examination categories M Physical examination and imaging; examination of bone marrow and categories cerebrospinal fluid may enhance the accuracy of appraisal Regional Lymph Nodes the regional lymph nodes are the preauricular, submandibular, and cervical lymph nodes. T1 Tumour confined to the retina with subretinal fluid no more than 5 mm from the base of any tumour, without retinal detachment T1a No tumour in either eye is greater than 3 mm in largest dimension or located closer than 1. The following are the procedures for assessing T, N, and M categories: T categories Physical examination and imaging N categories Physical examination M categories Physical examination and imaging Regional Lymph Nodes the regional lymph nodes are the preauricular, submandibular, and cervical lymph nodes. Hodgkin Lymphoma Introductory Notes the current staging classification for Hodgkin Lymphoma is a modification of the Ann Arbor classification first adopted in 1971. Over the past 45 years the practice has changed, making the previously used staging laparotomy and the resulting pathological staging classification obsolete. Clinical Staging (cS) It is determined by history, clinical examination, imaging, blood analysis, and the initial biopsy report. Bone marrow biopsy must be taken from a clinically or radiologically non involved area of bone. Liver Involvement Clinical evidence of liver involvement must include either enlargement of the liver and at least an abnormal serum alkaline phosphatase level and two different liver function test abnormalities, or an abnormal liver demonstrated by imaging and one abnormal liver function test. Spleen Involvement Clinical evidence of spleen involvement is accepted if there is palpable enlargement of the spleen confirmed by imaging. Lymphatic and Extralymphatic Disease the lymphatic structures are as follows: Lymph nodes Waldeyer ring Spleen Appendix Thymus Peyer patches the lymph nodes are grouped into regions and one or more (2, 3, etc. Lung Involvement Lung involvement limited to one lobe, or perihilar extension associated with ipsilateral lymphadenopathy, or unilateral pleural effusion with or without lung involvement but with hilar lymphadenopathy is considered as localized extralymphatic disease. Liver Involvement Liver involvement is always considered as diffuse extralymphatic disease. A and B Classification (Symptoms) Each stage should be divided into A and B according to the absence or presence of defined general symptoms. Unexplained weight loss of more than 10% of the usual body weight in the 6 months prior to first attendance 2. Night sweats Note Pruritus alone does not qualify for B classification nor does a short, febrile illness associated with a known infection. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non Hodgkin lymphoma: the Lugano classification. NonfiHodgkin Lymphomas the Lugano classification, a modification of the Ann Arbor classification, is recommended as for Hodgkin lymphoma with the exception of the elimination of the A or B classification of symptoms (see page 237). Paediatric Tumours Introductory Notes (see also page 13) the classifications in this section are not intended to replace the classifications used by the clinician when treating an individual patient but to facilitate the collection of stage by population based cancer registries. Well resourced registries may choose to collect additional accepted prognostic factors such as those used in the clinical setting but these are not included in this section. For some cancers, recommendations are the same as described earlier for adult patients and the appropriate page number is given; others are referenced where appropriate. Rules for Classification the classification applies only to paediatric malignant tumours. Gastrointestinal Tumours Hepatoblastoma Tier 1 and 2 Metastatic Distant metastases present Localized Tumour confined to the liver including regional lymph nodes 3 Well resourced cancer registries may wish to use the Pretext Classification. Prognostic Grouping the prognostic grouping for rhabdomyosarcoma includes favourable anatomic sites and unfavourable anatomic sites. Urological Tumours Testes Tier 1 Metastatic Distant metastases present Regional Tumour extension to regional lymph nodes Localized Tumour confined to the testes Tier 2 * See Classification for testes on page 195 for definitions of T category and N category. Well resourced cancer registries may wish to use the Classification on page 195 as used for adults that includes serum tumour markers. Wilms Tumour Tier 1 Metastatic Distant metastases present Localized Tumour confined to the area of origin Tier 2 Two Tier 2 staging classifications exist for Wilms Tumour. Ophthalmic Tumours Retinoblastoma Tier1 Metastatic Distant metastases present Regional Orbital extension or regional lymph nodes Localized Intraocular Tier2 this classification is determined after enucleation and is therefore a pathological classification. Paediatric cancer stage in population based cancer registries: the Toronto consensus principles and guidelines. Rules for Derivation of Paediatric Cancer Stage in Population Based Cancer Registries, according to the Toronto Consensus Principles and Guidelines. Brisbane, Australia: Viertel Cancer Research Centre, Cancer Council Queensland, in press. Medulloblastoma in children: a correlation between staging and results of treatment. E10-10677 Released May 2019 Texas Cancer Registry 2018/2019 Cancer Reporting Handbook Version 1. Texas Administrative Code, Title 25, Part 1, Chapter 91, Subchapter A (amended April 2017) specifies the rules necessary to implement this act. It is estimated that there will be 1,762,450 new cancers and 606,880 cancer deaths in the United States in 2019. Over 242,509 reports of cancer are received annually from over 600 hospitals, cancer treatment centers, ambulatory surgery centers, and pathology laboratories located throughout the state. The Texas Cancer Registry 2018-2019 Cancer Reporting Handbook serves as the instruction manual to provide rules and guidelines which assure the consistent collection and coding of relevant cancer case information. This edition should be used for reportable cases diagnosed January 1, 2018 and forward. Department of Health and Human Services National Institutes of Health National Cancer Institute. If the diagnosis year is unknown, use the year and month in which the case was accessioned. Also, refer to the 2018 Solid Tumor Rules and the Multiple Primary and Histology rules for site specific histology rules. Use the 2018 Solid Tumor coding rules to determine the number of primaries to abstract and the histology to code for cases diagnosed 1/1/2018 and forward. Third party software automatically convert these codes appropriately, for Web Plus users this is a manual process. If the diagnosis year is unknown, the correct guidelines for the year in which the case is accessioned must be used. Grade 2018 Grade Coding Instructions and Tables Beginning with cases diagnosed in 2018 grade information will be collected in three different data fields: Clinical Grade, Pathological Grade, and Post-Therapy Grade. The 2018 Solid Tumor Rules must be used for all sites mentioned in the General Guidelines. The 2018 Solid Tumor Coding Rules are a comprehensive revision to the 2007 site-specific Multiple Primary and Histology Rules, which were developed to promote consistent and standardized coding for cancer surveillance. When there is a tumor or tumors with separate microscopic foci, ignore the microscopic foci. Follow the Multiple Primary Rules; do not code multiple primaries based on biomarkers. Rules are divided into two sections: Single Tumor and Multiple Tumors Abstracted as a Single Primary a. Timing Rules Each Solid Tumor site group includes timing rules in the Multiple Primary Rules. Please see examples on page 8 in the Solid Tumor Rules 2018 General Instructions section. Please go to the 2018 Solid Tumor Rules for full coding instructions on all sites. Autonomic nervous system C479 has been added as a primary site for paragangliomas which are reported as malignant. It has been recognized that not all lung cancers are invasive /3 so new codes were implemented. Please see the 2018 Solid Tumor Rules for more information and for full coding instructions for all sites above. Further action, which may include cost recovery procedures, will be instituted if submissions continue to be delinquent. These actions are necessary to meet the state and national requirements for timely cancer data submissions. To be compliant with the law, all records must be submitted within 6 months of initial diagnosis, or admission with active disease, or treatment for cancer at your facility. The data are privileged and may not be divulged or made public in a manner that discloses the individual identity of any patient. All reporting entities that are performing in compliance with the Act are immune from civil and criminal liability for furnishing the required information. A Web Query Tool which generates customized maps and tables of Texas cancer incidence and mortality rates is also available on the website at. However, no facility-specific patient information can be released unless authorized under law. Requests for training and technical assistance should be directed to the Austin Central Office Training Specialist Lead Worker. The pilot originally consisted of inpatient/outpatient and Texas deaths which showed facility visits that did not reflect a cancer billing code. This did not yield significant missed cases for the amount of work for reporters and moving forward this process will only include inpatient and outpatient visits with cancer billing codes and Texas deaths linkage results. In addition, this data will also be available to use in cancer surveillance, program planning, and evaluation activities. Once the linkage is complete, each facility will be provided with a listing of potentially missed cases for your review, abstraction, and submission. This process combines the Death Clearance Only Audit performed in previous years as well as Casefinding Data Quality Audits. This will eliminate multiple listing requests for facilities and it will be performed annually. With this data submission method you must obtain a Web Plus account by completing the Online Web Plus Account Registration and submitting the Web Plus Use and Confidentiality Statement via fax at 512-776-7681, or scan and email. Other fields which are encouraged if available are race/ethnicity and primary payer. Before choosing this method, please consider one of the more secure electronic methods discussed previously. Please reference our Who Do I Call list for the appropriate representative to call if you have additional questions. Active casefinding: the personnel responsible for reporting obtain and review all sources for eligible cases. A combination of active and passive casefinding is a more effective method and ensures fewer missed cases. It is strongly recommended that every facility have a Casefinding Policy and Procedure in place. The procedures should be evaluated from time to time and amended as facility procedures or services change. Bone Marrow reports 30 Texas Cancer Registry 2018/2019 Cancer Reporting Handbook Version 1. The reporter is responsible for identifying all casefinding sources under their facility licensure and arranging access to these sources, for example, rural health clinics, surgery centers across town or off campus. Electronic Disease Indices in Excel format is preferred and should include a *non- reportable column. Please note that the Excel format *Non Reportable column should be marked if it is deemed to be a non- reportable. The indices must include both inpatient and outpatient admissions and must be based on year of admission. Change the sequence number to reflect the new primary and abstract the pertinent cancer information. This disease index is then checked against the cancer registry database to ensure that all cases were either reported or clearly documented as non-reportable with the reason it is not reportable. Instructions for Reporting Solid Tumors Instructions in this section apply to solid tumors. A clinical diagnosis may be recorded in the final diagnosis, on the face sheet, in a clinic note, or in other parts of the medical record. If the patient has a biopsy or fine-needle aspiration that disproves the clinical diagnosis the case is not reportable. Exception: If enough time has passed that it is reasonable to assume that the physician has seen the negative pathology report, and the clinician continues to call this a reportable disease, accession the case. A fine-needle aspiration is non-diagnostic and the physician advises the patient to have further tests. In September 2018 the physician sees the patient again and states that this is probable lung cancer based on previous x-rays, continued symptoms, and further decline in health. Any carcinoma arising in a hemorrhoid is reportable since hemorrhoids arise in mucosa, not in skin. Each facility should consult their cancer committee, physician advisor, and pathologists to determine how the phrase is used within the facility. Report mature teratoma of the testis when diagnosed after puberty (malignant) and do not report when diagnosed in a child (benign). Do not report Mature Teratoma of the testis when it is not known whether the patient is prepubescent or postpubenscent. For testis: Mature teratoma in adults is malignant (9080/3); therefore, is a reportable neoplasm. Assign 8150/3 unless specified as a neuroendocrine tumor, Grade 1 (8240/3) or neuroendocrine tumor, Grade 2 (8249/3). Rathke pouch tumor (C751, 9350/1) is a reportable neoplasm for cases diagnosed 2004 and later. The fact that no residual malignancy was found in the later specimen does not disprove the malignancy diagnosed by the biopsy. Note: An exhaustive immunohistochemical work-up shows no melanocytic, epithelial or vascular differentiation.
Some of the patagia are common sites of chronic ulcerative dermatitis lesions (modified from Lucas and Stettenheim32) chronic gastritis risks generic gasex 100 caps without prescription. The opening to the gland is 3) ventral region of neck 19) vent frequently surrounded by a tuft of feathers (open arrow) gastritis diet 4 believers buy cheap gasex 100 caps on line. Additional secretions from the skin and the 8) left ulnar region 24) left posterior shank region uropygial gland are believed to suppress the growth 9) left wrist region 25) left lateral shank region 10) left region of metacarpus syarat diet gastritis buy 100caps gasex with amex, 26) left anterior shank region of microorganisms gastritis diet x1 purchase genuine gasex online. These anatomic areas as well as include neoplasm (primarily squamous cell or adeno- the ventral tail region appear to be frequent sites for carcinoma) gastritis diet meal plan buy discount gasex 100 caps line, abscessation and impactions gastritis diet queen gasex 100caps with amex. The uropygial gland is a bilobed gland located at the Impacted glands are frequently discussed in the lit- base of the tail dorsal to the pygostyle gastritis diet харьков order gasex canada. The absent in many Columbiformes gastritis diet questionnaire order gasex with visa, Amazon parrots and gland is normally swollen and appears as though it other Psittaciformes. In some birds, hyperkeratotic the outside through a caudally directed nipple that is plugs may form in the gland. These cases will gener- frequently surrounding by a tuft of feathers (Figure ally respond to removal of the plug and improving the 24. The division between feather tracts is evident on the back of this lutino cockatiel with pruritic dermatitis (courtesy of Louise Bauck). The pennaceous portion of feather (arrow) and plumaceous portion of feather (open arrow) are also evident. The pen- respond to extensive treatment that included laser naceous and plumaceous portions of the feather form the vane therapy, but recovered three months later after a (modified from Lucas and Stettenheim32). Feathers may Surgical extirpation of the gland may be necessary if also function in courtship, defense (color mimicking) neoplasia occurs (see Chapter 41). In most birds, ing the gland will cause the birds to lose the ability the body is divided into areas that contain feather to waterproof their feathers. In other birds, removal tracts (pterylae) and areas that do not contain of the gland seems to have few clinically detectable feather tracts (apteria) (Figure 24. The posterior barbules contain ridges, to which the anterior barbicels are attached in a zipper-like fashion. A feather appears as a unified sheet of tissue because of the interlocking barbules that hold the barbs to- gether to form the vane on either side of the feather shaft. The interlocking nature of the barbules serves to wa- terproof the feathers, forming a type of thatched roof (Figure 24. The interlocking barbules also serve to improve the insulating capacity of the feathers and create an aerofoil to facilitate flight (see Chapter 8). These lesions are frequently the feathers can be characterized blamed on an enclosure of insufficient size. The central shaft of the feather is called the based on the structure of the rachis, rachis (arrow). The barbs are connected barbs and barbules, and are divided to each other by the barbules. They are the largest feathers and have a well devel- oped shaft, pennaceous and plu- mulaceous components of the vane and an afterfeather. Coverts are the small contour feathers that are found in rows on the wing and tail. The 2) posterior barbules contain 3) ridges that connect with the hooks (open Remiges are large, stiff, well de- arrow) found on the 4) anterior barbules. This interlocking mechanism makes the feathers waterproof and improves their insulating capacity. The spaces between the tracts can facilitate the ally asymmetric in form and have clinical evaluation of the skin. The remiges that region and its underlying integumentary compo- arise from the periosteum of the metacarpus are nents is called an apterium. The Terms used to describe parts of a feather are listed in primaries are counted from proximal to distal (dig- Table 24. The the feather is composed of a long, central tapering number of primary and secondary feathers varies shaft that is divided into the hollow base (quill, cala- among species. Bristles are characterized by a stiff, tapered rachis with no barbs except at the proximal end. They are usually found around the mouth, nostrils and eyes and are believed to serve a sensory func- tion. The follicu- lar wall has an abundant supply of sensory nerve fibers, and the papil- lae, pulp and feather muscles are also well innervated. Definitive down feathers occur on various parts of the body as part of the adult plumage. Powder down are specialized down feathers that disintegrate and produce a powder (keratin) that Rachis the long, solid, tubular portion of the shaft above the skin. It is a thickened continuation of the calamus is spread through the feathers during preening. The rachis contains pith, They are found throughout the body among the which is composed of air-filled keratinized epithelial down and contour feathers. The calamus and der down feathers frequently have soiled-appear- proximal portion of the rachis are vascularized in the developing feather (pin feather). Vane or the portion of the feather that extends to either side of vexillum the rachis and is composed of the barbs and their Semiplumes have a long rachis and entirely plu- associated structures. They occur in feather tracts of (soft, downy) or pennaceous (compact and closely knit) their own or are found along the margins of con- depending on the individual type of feather. Pulp the mesodermal component of the growing feather consisting of vascular connective tissue. The pulp re- Hypopnea (afterfeathers) are structures at- gresses as the feather grows and is absent in the tached to the underside of a feather at the superior normal mature feather. They may consist only of barbs or have Pulp caps Keratinizing epidermis that covers the distal extremity a shaft and plumulaceous barbs. As the pulp regresses, the keratinized caps Filoplumes are fine, hair-like feathers with a remain and are visible as horizontal bars crossing the lumen of the calamus. Some red coloration in the appendages Pigments of birds is caused by vascularization and not pigment Melanins disposition. When combined, create black, brown, red- dish brown, yellow, red, purple and chestnut red-appear- blanching can be used to determine if an area is ing colors. Carotenoids the normal iridescent glow of the feathers may be Bright red, orange, yellow. Cannot be synthesized and induced in part by lipids derived from the keratino- must be derived from ingested plants. It is interesting to note that abnormally colored Noniridescent colors do not change with the angle of view feathers may return to normal without a molt. As birds electroencephalographic activity following the re- respond to therapy for hepatitis, these feathers will moval of feathers suggest that it is a painful proce- 16 return to a normal white coloration, presumably be- dure. Clinically, the removal of a feather will fre- cause biliverdin-laden, keratinocyte-produced lipids quently stimulate movement in an anesthetized bird are replaced with lipids that do not contain at the same anesthetic plane that can be used to biliverdin. Yellow or red pigments derived from the uropygial Feather Color gland can be spread on the feathers where the pig- the color of feathers is determined by two factors: the ment remains bright until it fades due to oxidation pigments that are deposited at the time of develop- from exposure to air and light. In a healthy bird, ment, and structural features of the feather that alter feathers maintain their bright pigmentation through the absorption or reflection of light (Table 24. These the addition of newly synthesized oils during preen- structural features of the feather can be inherent in the ing. These mechanisms for imparting color to a development of the feather or can be induced by mate- feather would allow changes in feather pigmentation rials that are placed on the feathers after development. Birds If a feather reflects all wavelengths of light, it appears receiving higher fat diets would be expected to pro- white; if it absorbs all wavelengths of light, it appears duce a lipid-rich, keratinocyte-derived uropygial black. Dark-colored feathers appear to be more durable gland secretion that may enhance the color and than light-colored ones. The pigmentation of feathers may serve to absorb or In poultry, a lack of pigmentation (achromia) has repel heat (light), warn predators, act as a camouflage been associated with dietary deficiencies in lysine, or function in mating displays. Lysine deficiency has not been barbs and barbules to scatter and reflect varying wave- found to alter the pigmentation of cockatiel feathers lengths of light causes the iridescent glow of the feath- but deficiencies of choline or riboflavin will cause ers. Blue colors are created by the barbs interacting to abnormal pigmentation (see Chapter 31). Both reflect blue light while allowing other wavelengths of melanism and albinism have been reported in a vari- light to be absorbed by darker melanin granules. Abnormal yellow, red and pink feath- ers may be noted in Amazon parrots and African Grey Parrots, and it has been suggested that these are associated with hepatopathies, renal dysfunction or systemic disease. Psittacine beak and feather dis- ease has been implicated in some cases of the abnor- mal occurrence of red feathers in African Grey Par- rots. Molt Soft keratin structures (skin, comb, wattles, cere) undergo constant replacement through the slough- ing of the outer cornified layer (Figure 24. Old or damaged outer layers of hard keratin structures (rhamphotheca and metatarsal spurs) are replaced through normal wear. The thick, horny heel pads on the back joints of woodpecker, toucan and barbet neonates are molted at fledging. In cases of malnu- trition or systemic disease, hyperkeratotic layers of the rhamphotheca can accumulate and be peeled off with a blunt instrument. Molting is the process whereby the growth of a new feather causes the shedding of an old feather. The single generation of feathers that occurs as a result of a molt is collectively known as plumage. Excessively dry, flaky skin can be an indication of malnutrition or organopathies. In this cockatoo, a heavy molt and ers present on the body at one time, regardless of sloughing of sheets of the epidermis were induced by changing the when they first appeared, are called the feather coat. A new feather that is still enclosed in a feather and is strictly dependent on the developing genera- sheath is called a pin feather (Color 24. The physi- tion of feathers; thus, the pattern of molt should be cal characteristics and appearance of the feather are defined based on the developing feathers (which con- controlled by factors that affect the development of trol the molt cycle) and not on the shedding of a the feather at the edge of the epidermal collar. Any feather (which has nothing to do with the molt unless infectious agent or systemic abnormality that alters the feather has been mechanically removed). Additionally, Molting Periods damage to the epidermal collar will be manifested the molting process can be divided into periods. The devel- second plumage (the first plumage would be the na- oping feather is composed of the outer epidermis and tal down). The barb ridges, rachis and hypo- smaller than an adult because the feathers are re- rachis are formed by the epidermis as it grows longi- duced in length and width at this stage of develop- tudinally. A molt cycle is defined as the period that runs from the appearance of a plumage to the appearance of its replacement. The cycle length for most birds is one year; however, some species will molt throughout the year, while others will molt annually or several times a year during distinct periods. Most authors theo- rize that replacement of the adult plumage is syn- chronized with the gonadal cycles and will be longer or shorter than one year based on reproductive activ- ity; however, molting may be more dependent on photoperiod. Domesticated birds that reproduce year round under artificial lighting conditions may not undergo the seasonal molt that would be expected to occur in their free-ranging conspecifics. The wings and progresses until about half of the prima- bird was placed on a formulated diet and the newly developing ries are replaced. The body feathers begin to molt after the wing feathers are growth, it might become increasingly sensitive to actively being replaced. The tail feathers are re- certain secretions (thyroid hormone, sex hormones) placed from the central feathers outward. By having that could then potentiate the growth of a new a progressive molt, birds are able to continue flying feather. In some water- fowl and seabirds, all of the flight and tail feathers the occurrence of a cyclic rather than systemically are replaced at one time, and these birds go through controlled molt seems clinically feasible given that a period of flightlessness. The feathers appear to molt in sections Malnutrition can impact the speed of molt and the starting with the head, neck and thorax, followed by health of the developing feathers. Birds that are on diets that contain insuffi- lae may undergo several plumage replacements be- cient energy or protein might undergo a partial molt fore any feathers are molted from another area. The process probably involves nutrition and environmental or disease-related a combination of hormonal, seasonal, nutritional and stress factors. The effects of individ- generation of feathers on the head and neck, with ual hormones on the molt cycle appear to vary widely several generations of old feathers on the wings and among avian genera, and information derived from body (Figure 24. This hormone may affect the shape, struc- General Diagnosis ture, formation of pigment, color patterns and rate of growth of feathers. In fowl, administration of thyroid and Therapy hormone may induce a molt in seven or eight days. If the thyroid is removed, feather formation on the body stops but the molt of wing feathers will continue, suggesting that their replacement is not controlled Investigation of Dermatologic Disease by thyroid hormone. Administration of high concen- Integumentary diseases can be broadly classified as trations of thyroxine will increase the speed of the being caused by infectious or noninfectious agents molt cycle. In many cases, dermatologic lesions are mone is important in initiating a molt; however, secondarily infected with bacterial or fungal agents, other studies indicate that progesterone and pro- and the identification of microbial agents from cul- lactin can induce a molt without a change in circulat- tures of the skin does not necessarily implicate these ing levels of thyroid hormone. In a study of King Penguins, it was found that thy- Using a dermatology examination form is a concise roxine levels rose significantly (five times resting way to consistently evaluate and record integumen- levels) during the molting period, and corticosterone tary lesions. By (as measured by thyroidal uptake of radioactive iodine) using a standardized form and evaluation system, did not differ appreciably between molting and non- avian veterinarians and dermatologists can more ef- molting hens. These apparent conflicts in experimental fectively quantify and compare their findings, which findings may suggest that research protocols, no mat- will ultimately lead to improved clinical description, ter how effectively conceived, may not accurately re- diagnosis and treatment of skin and feather diseases. The predilection to develop certain types of integu- Feather formation is prevented by circulating estro- mentary diseases may vary among species (Table gens. The diagnostic evaluation used for avian der- follicles that are already replacing a feather but will matologic diseases is similar regardless of the etiol- not stimulate feather development. The evaluation of feather and skin gish and prolonged in fowl exposed to 12 to 14 hours lesions, particularly in small birds, can be facilitated of light. Inflammation of the companion birds that originate from widely varying skin can occur as a result of trauma, chemical irrita- geographic regions is undetermined. Molting activity can be induced by high doses of medroxyprogesterone, de- Cytology, culture and biopsy are indicated in cases of creased exposure to light or administration of thyrox- dermatitis. Birds that are stressed by handling during Protozoal Irradiation a molt may lose more feathers than birds that are in Metazoal (parasitic) Neoplastic a relaxed atmosphere. Some birds are able to release Immune-mediated Behavioral feathers when being restrained (fear or stress molt). Neoplasia including melanomas Identifying and correcting any behavioral abnor- Ratites Poxvirus malities that are causing over-grooming (feather Malnutrition picking). Skin lesions should be kept clean, and creams, lotions any scabs, moistening the culturette in the sterile or solutions can be used to moisturize and sooth dry, transport media and rolling the tip over the lesion. Moistened swabs will yield better results than dry Any medications placed on a wound should either kill ones, and it is important that the swab be plated as specific target microorganisms or protect healing tis- soon as possible after collection. Ointments and oily compounds interfere with sive diagnostic technique in practice is to apply a normal feather function and should be avoided (Color microscope slide to the affected area and to examine 24. Skin biopsies are iodine compounds for example, are effective in con- most diagnostic if collected from the center and the trolling bacteria, but may also impair healing by periphery of the lesion. A mixture gars and occasionally in large Psittaciformes (see of Penetran and aloe vera may relieve severe pruri- Chapter 32). If a bird does not improve within 48 hours of initiating therapy, the preparation should be consid- premature molting of the wing and tail feathers and ered ineffective and discontinued. It should be noted that any factor (infectious or however, surgery should not be considered until all noninfectious) that damages the epidermal collar can other therapeutic modalities have failed to resolve result in a gross lesion resembling that induced by the lesions over a six-month treatment period. Techniques that are discussed in the lay literature, including dietary additives and careful selection of Lesions should be evaluated regularly (generally on breeding stock, are probably futile. Good hygiene is a weekly basis) to determine if prescribed therapy is advisable, and birds should be purchased from effective. Poxvirus can cause skin lesions in most avian species and may retard wound healing. Uncomplicated le- sions are characterized by the formation of nodules on the unfeathered skin. Skin lesions should be kept clean and dry to prevent secondary bacterial or fun- Specific Etiologies of gal infections (see Chapter 32). Generalized Dermatopathies Cutaneous papillomas may occur on the head, neck, beak commissure, feet or uropygial glands. Some of these lesions have been associated with papil- Viral Diseases lomavirus or herpesvirus while others are of undeter- mined etiology. The ally attack birds causing characteristic hyperemic disease progression can be acute or chronic depending swellings (Color 24. The likelihood of a bird being stung can be reduced by removing uneaten soft foods (particularly fruits) from the enclosure and destroying wasp nests found near the aviary. Flies, mosquitoes and gnats can cause severe derma- titis on the face, feet and legs, particularly in birds raised in warm coastal areas (see Color 26). Lesions are most common in Amazon parrots and macaws, but can occur in any species. The flies that commonly parasitize cattle and deer can induce small bleeding ulcers on the unfeathered areas of the body (Color 24.
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