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Τρίτη, 3 Ιανουαρίου 2017

Metastatic neuroendocrine tumor with initial presentation of orbital apex syndrome


Volume 7, March 2017, Pages 9–11
Open Access

Highlights

The etiologies of orbital apex syndrome are broad and the adequate management depends on the exact diagnosis.
The use of corticosteroids is reasonable in patients without obvious infection and cancer history.
Obtaining a biopsy-proven evidence is warranted in patients with orbital apex syndrome.
Searching for possible primary origin or systemic metastases is important in patients with neuroendocrine tumors.

Abstract

The possible etiologies of orbital apex syndrome range from inflammatory, infectious, neoplastic, iatrogenic/traumatic, to vascular processes. In patients without obvious infection or systemic cancer history, judicious use of corticosteroids is a reasonable strategy. We describe a 64-year-old man who presented with orbital apex syndrome and had progressed to total visual loss in three days after admission. Radiological imaging and pathological studies were consistent with a neuroendocrine tumor with multiple metastases. We recommend that a biopsy-proven specimen is warranted in patient with orbital apex syndrome even without a cancer history.

Keywords

  • Orbital apex syndrome
  • Neuroendocrine tumor
  • Corticosteroids

1. Introduction

Lesions affecting the anatomically adjacent structures, including optic nerve (II), oculomotor nerve (III), trochlear nerve (IV), abducens nerve (VI), ophthalmic/maxillary branch of the trigeminal nerve (V1, V2) and oculosympathetic fibers, may cause three partially overlapping clinical syndromes: superior orbital fissure, orbital apex, and cavernous sinus syndrome. The etiologies causing these syndromes are also quite similar, i.e., inflammatory, infectious, neoplastic, iatrogenic/traumatic, or vascular processes. Based on the broad spectrum of etiologies, the decision on evaluation and management remains a great challenge to clinical physicians [1]. For example, the use of corticosteroids is warranted for inflammatory process, but may be harmful to some infection etiologies. Also, conservative measures may be adequate for some causes, whereas urgent procedures are necessary in others.
Possible primary tumors involving the orbital apex and cavernous sinus include lymphoma, neural tumors and local invasion from adjacent head and neck tumors. The metastatic tumors include the origins from breast, lung, kidney and malignant melanoma. Some inflammatory causes, like orbital pseudotumor, Tolosa-Hunt syndrome, and thyroid orbitopathy, may mimic neoplasms [1][2] and [3]. Among the neoplasms, neuroendocrine tumor is relatively rare and usually arises from gastrointestinal tract or bronchopulmonary source [4]. Here, we reported a rare case of high grade neuroendocrine tumor of unknown primary site with initial presentation of progressive ptosis and vision loss as orbital apex syndrome, which highlighted the importance of obtaining biopsy-proven specimen in such patients.

2. Case report

A 64-year-old man was previously healthy and was referred to neurological clinic for ptosis in the left eye. He had acute onset of ptosis, retro-orbital soreness and mild blurred vision on the left side for one month. There was no double vision and motor or sensory symptoms. There was also no fever, rhinorrhea, nose stuffy, and tinnitus. The orbital symptoms had progressed gradually without obvious diurnal change. Neurologic examinations showed left ptosis, mild palpebral swelling without erythematous change, sluggish light reflex and slight upper ward gaze limitation in the left eye. The visual acuity was 6/10 in the right eye and 6/12 in the left eye on the day of admission. The symptom had progressed rapidly within three days that there was no light perception and full dilated pupil without light reflex in his left eye. The laboratory tests for inflammation and infection, including complete blood count with differential count, erythrocyte sedimentation rate, C-reactive protein, were normal. The serologic studies, including liver and renal function, along with carcinoembryonic antigen and alpha-fetoprotein, were also normal. The acetylcholine receptor antibody was within normal range. The magnetic resonance imaging of brain revealed a prominent left cavernous sinus with increasing soft tissue component that anteriorly extended into the orbital cavity, and heterogeneous enhancement in the retrobulbar space. Trace enhancements in the intracavernous and retrobulbar spaces were also depicted (Fig.1). He underwent sphenoethomoidectomy, and a dark reddish tumor was found at the opticocarotid recess. The pathology of the tumor showed large polygonal cells with hyperchromatic nuclei, distinct nucleoli and moderate pink cytoplasm (Fig. 2), and immunoreactivity to several immunohistochemical stainings, including cytokeratin, neuron-specific enolase, synaptophysin and chromogranin A, which were compatible with a neuroendocrine tumor. Positron emission tomography/computed tomography (PET/CT) scan showed increased multiple uptakes at the left orbital area, spines, rib cages and liver (Fig.3). Echo-guided liver biopsy revealed the same high grade malignant tumor with neuroendocrine differentiation. The primary site of the tumor was unclear. The patient died six months after initial symptoms.
Fig. 1
Fig. 1. 
Coronal contrast and noncontrast T1 weighted images (A, B), axial contrast T1 weighted image (C), and axial T2 weighted image (D). These pictures showed the heterogeneous soft tissues within the orbital apex, extending to orbital canal and cavernous sinus (arrows).
Fig. 2
Fig. 2. 
The tumor tissue composed of large polygonal cells with hyperchromatic nuclei, distinct nucleoli and moderate pink cytoplasm (H&E stain, 400 ×). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 3
Fig. 3. 
Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG PET/CT) showed intense uptake in left retro-orbital region and paranasal sinus. The intense uptake also involved the spine, rib cage, pelvic bones, bilateral femora and both lobes of liver.

3. Discussion

The orbital apex tumors range from benign inflammatory process to high grade malignancy. Ocular symptom is the initial manifestation of metastatic orbital tumors in up to 25% [5]. The diagnosis may be difficult in patients without history of systemic cancers. Neuroendocrine tumors are rare among the metastatic orbital tumors, and the clinical manifestation may masquerade cellulitis [2] or Graves orthopathy [3]. Furthermore, metastases are found in about 20% of the patients with neuroendocrine tumors at the time of diagnosis [6]. Similar to our patient but with a different scenario, a patient was reported previously with an unknown origin of neuroendocrine tumor in liver and was found to have orbital metastasis on both sides six month later [7].
When the cause of orbital apex is unable to be determined, possible management options include observation, an empirical trial of corticosteroid, and surgical biopsy. Because the distinctions among inflammation, infection, and neoplasm are often difficult and all may respond initially to corticosteroids, a short period of therapeutic corticosteroid trial has been suggested in the patients without systemic signs of infection or cancer history [1]. Because of the acute onset of symptoms with rapid progression that seemed to be more typical of an inflammatory process, a trial of corticosteroid was considered and used. After excluding the possibility of a vascular source by images and obtaining sufficient support of biopsy technique, a fine needle biopsy was considered at first. Because of rapidly loss of vision, however, sphenoethomoidectomy was done for the additional purpose of decompression. Without the tissue proof, the strategy of corticosteroid use may delay the diagnosis and further management in our patient.
From this experience, we recommend that a tissue proof may need to be considered first if the surgical risk is not high or the vision loss or ophthalmalgia is progressing rapidly. Pathological evidence is crucial for the diagnosis in patients with orbital apex syndrome, and an immunohistochemistry study may be helpful in identifying a neuroendocrine origin. When the neuroendocrine tumor is confirmed, further investigations of primary origin and possible systemic metastases are mandatory.

Conflicts of interest/disclosures

The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.

References

    • [4]
    • D.J. Shetlar, R.L. Font, N. Ordonez, A. el-Naggar, M. Boniuk
    • A clinicopathologic study of three carcinoid tumors metastatic to the orbit. Immunohistochemical, ultrastructural, and DNA flow cytometric studies
    • Ophthalmology, 97 (1990), pp. 257–264
    •  |   |   | 
Corresponding author at: 95 Wen-Chang Road, Shin-Lin District, Taipei, Taiwan.

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Tinnitus

1. Chadha NK, Gordon KA, James AL, Papsin BC. Tinnitus is prevalent in children with cochlear implants. International Journal of Pediatric Otorhinolaryngology. 2009;73:671-675. [abstract]

2. Akdogan O, Ozcan I, Ozbek C, Dere H. Tinnitus after cochlear implantation. Auris Nasus Larynx. 2009;36:210-212. [abstract]

3. Pan T, Tyler RS, Ji H, Coelho C, Gehringer AK, Gogel SA. Changes in the tinnitus handicap questionnaire after cochlear implantation. American Journal of Audiology. 2009;18:144-151. [abstract]

4. Andersson G, Freijd A, Baguley DM, Idrizbegovic E. Tinnitus distress, anxiety, depression, and hearing problems among cochlear implant patients with tinnitus. Journal of the American Academy of Audiology. 2009;20:315-319. [abstract]

5. Rothholtz VS, Tang Q, Wu EC, Fine EL, Djalilian H, Zeng F-G. Exploring the parametric space of tinnitus suppression in a patient with a cochlear implant. Laryngoscope. 2009;119.

6. Di NW, Cianfrone F, Scorpecci A, Cantore I, Giannantonio S, Paludetti G. Transtympanic electrical stimulation for immediate and long-term tinnitus suppression. International Tinnitus Journal. 2009;15:100-106.[abstract]

7. Litre CF, Theret E, Tran H et al. Surgical treatment by electrical stimulation of the auditory cortex for intractable tinnitus. Brain Stimulation. 2009;2:132-137. [abstract]

8. Evans RW, Ishiyama G. Migraine with transient unilateral hearing loss and tinnitus. Headache: The Journal of Head & Face Pain. 2009;49:756-759. [abstract]

9. Pirodda A, Brandolini C, Raimondi MC, Ferri GG, Borghi C. Tinnitus as a warning for preventing vasovagal syncope. Medical Hypotheses. 2009;73:370-371. [abstract]

10. Anderson JE, Teitel D, Wu YW. Venous hum causing tinnitus: case report and review of the literature. Clinical Pediatrics. 2009;48:87-89. [abstract]

11. Liess BD, Lollar KW, Christiansen SG, Vaslow D. Pulsatile tinnitus: a harbinger of a greater ill? Head & Neck. 2009;31:269-273. [abstract]

12. Singh DP, Forte AJ, Brewer MB, Nowygrod R. Bilateral carotid endarterectomy as treatment of vascular pulsatile tinnitus. Journal of Vascular Surgery. 2009;50:183-185. [abstract]

13. Delgado F, Munoz F, Bravo-Rodriguez F, Jurado-Ramos A, Oteros R. Treatment of dural arteriovenous fistulas presenting as pulsatile tinnitus. Otology and Neurotology. 2009;30:897-902. [abstract]

14. Cowley PO, Jones R, Tuch P, McAuliffe W. Pulsatile tinnitus from reversal of flow in an aberrant occipital artery: Resolved after carotid artery stenting. American Journal of Neuroradiology. 2009;30:995-997. [abstract]

15. Stimmer H, Borrmann A, Loer C, Arnold W, Rummeny EJ. Monaural tinnitus from a contralateral inferior colliculus hemorrhage. Audiology & Neurotology. 2009;14:35-38. [abstract]

16. Latifpour DH, Grenner J, Sjodahl C. The effect of a new treatment based on somatosensory stimulation in a group of patients with somatically related tinnitus. International Tinnitus Journal. 2009;15:94-99. [abstract]

17. Department of Health. Provision of services for adults with tinnitus: a good practice guide. 2009. [full text]

18. DH. Tinnitus Map of Medicine care pathway. 2010. [Full text]

19. BTA. Tinnitus: guidelines for primary care. 2010. [Full text]

20. Schneider P, Andermann M, Wengenroth M et al. Reduced volume of Heschl's gyrus in tinnitus. NeuroImage. 2009;45:927-939. [abstract]

21. Landgrebe M, Langguth B, Rosengarth K et al. Structural brain changes in tinnitus: grey matter decrease in auditory and non-auditory brain areas. NeuroImage. 2009;46:213-218. [abstract]

22. Melcher JR, Levine RA, Bergevin C, Norris B. The auditory midbrain of people with tinnitus: Abnormal sound-evoked activity revisited. Hearing Research. 2009;257:63-74. [abstract]

23. Lanting CP, de KE, van DP. Neural activity underlying tinnitus generation: Results from PET and fMRI. Hearing Research. 2009;255:1-13. [abstract]

24. Kaltenbach JA. Insights on the origins of tinnitus: an overview of recent research. Hearing Journal. 2009;62:26-31. [Full text]

25. Shulman A, Goldstein B, Strashun AM. Final common pathway for tinnitus: theoretical and clinical implications of neuroanatomical substrates. International Tinnitus Journal. 2009;15:5-50. [abstract]

26. Schutte NS, Noble W, Malouff JM, Bhullar N. Evaluation of a model of distress related to tinnitus. International Journal of Audiology. 2009;48:428-432. [abstract]

27. Hesser H, Pereswetoff-Morath CE, Andersson G. Consequences of controlling background sounds: the effect of experiential avoidance on tinnitus interference. Rehabilitation Psychology. 2009;54:381-390.[abstract]

28. Argstatter H, Krick C, Bolay HV. Music therapy for chronic tinnitus. Heidelberg treatment model. Psychotherapeut. 2009;54:17-26. [abstract]

29. Lugli M, Romani R, Ponzi S, Bacciu S, Parmigiani S. The windowed sound therapy: A new empirical approach for an effective personalized treatment of tinnitus. International Tinnitus Journal. 2009;15:51-61.[abstract]

30. Langguth B, Salvi R, Elgoyhen AB. Emerging pharmacotherapy of tinnitus. Expert Opinion on Emerging Drugs. 2009;14:687-702. [abstract]

31. Campbell KCM. Emerging pharmacologic treatments for hearing loss and tinnitus. ASHA Leader. 2009;14:14-18. [Full text]

32. Hesser H, Westin V, Hayes SC, Andersson G. Clients' in-session acceptance and cognitive defusion behaviors in acceptance-based treatment of tinnitus distress. Behaviour Research & Therapy. 2009;47:523-528. [abstract]

33. Hesser H, Andersson G. The role of anxiety sensitivity and behavioral avoidance in tinnitus disability. International Journal of Audiology. 2009;48:295-299. [abstract]

34. Shulman A, Goldstein B. Subjective idiopathic tinnitus and palliative care: a plan for diagnosis and treatment. Otolaryngologic Clinics of North America. 2009;42:15-38. [abstract]

35. Forti S, Costanzo S, Crocetti A, Pignataro L, Del BL, Ambrosetti U. Are results of tinnitus retraining therapy maintained over time? 18-month follow-up after completion of therapy. Audiology & Neuro-Otology. 2009;14:286-289. [abstract]

36. Bessman P, Heider T, Watten VP, Watten RG. The tinnitus intensive therapy habituation program: a 2-year follow-up pilot study on subjective tinnitus. Rehabilitation Psychology. 2009;54:133-138. [abstract]

37. Gudex C, Skellgaard PH, West T, Sorensen J. Effectiveness of a tinnitus management programme: A 2-year follow-up study. BMC Ear, Nose and Throat Disorders. 2009;9. [Full text]

38. Henry J, Zaugg T, Myers P, Kendall C, Turbin M. Principles and application of educational counseling used in progressive audiologic tinnitus management. Noise and Health. 2009;11:33-48. [abstract]

1. Hazell JW, Jastreboff PJ. Tinnitus. I: Auditory mechanisms: a model for tinnitus and hearing impairment. J Otolaryngol. 1990;19:1-5. [Abstract]

2. Jastreboff PJ, Jastreboff MM. Tinnitus Retraining Therapy (TRT) as a method for treatment of tinnitus and hyperacusis patients. J Am Acad Audiol. 2000 Mar;11(3):162-77. [Abstract]

3. Marcondes RA, Sanchez TG, Kii MA, Langguth et al. Repetitive transcranial magnetic stimulation improve tinnitus in normal hearing patients: a double-blind controlled, clinical and neuroimaging outcome study. Eur J Neurol. 2009. [Epub ahead of print] ) [Abstract]

4. Cannon SC Pathomechanisms in channelopathies of skeletal muscle and brain. Annu Rev Neurosci. 2006;29:387-415. [Abstract]

5. Davies E, Knox E, Donaldson I. The usefulness of nimodipine, an L-calcium channel antagonist, in the treatment of tinnitus. Br J Audiol. 1994;28:125-129. [Abstract]

6. Baguley DM, Jones S, Wilkins I, Axon PR, Moffat DA. The inhibitory effect of intravenous lidocaine infusion on tinnitus after translabyrinthine removal of vestibular schwannoma: a double-blind, placebo-controlled, crossover study. Otol Neurotol. 2005;26:169-176. [Abstract]

Eggermont JJ. Cortical tonotopic map reorganization and its implications for treatment of tinnitus. Acta Otolaryngol Suppl. 2006;9-12. [Abstract]

Hoke ES, Muhlnickel W, Ross B, Hoke M. Tinnitus and event-related activity of the auditory cortex. Audiol Neurootol. 1998;3:300-331. [Abstract]

Mirz F, Pedersen B, Ishizu K et al. Positron emission tomography of cortical centers of tinnitus. Hear Res. 1999;134:133-144. [Abstract]

Muhlnickel W, Elbert T, Taub E, Flor H. Reorganization of auditory cortex in tinnitus. Proc Natl Acad Sci U S A. 1998;95:10340-10343. [Abstract]

Norena AJ, Eggermont JJ. Enriched acoustic environment after noise trauma abolishes neural signs of tinnitus. Neuroreport. 2006;17:559-563. [Abstract]

Schlee W, Hartmann T, Langguth B, Weisz N. Abnormal resting-state cortical coupling in chronic tinnitus. BMC Neurosci. 2009;10:11. [Full text]

Schlee W, Mueller N, Hartmann T, Keil J, Lorenz I, Weisz N. Mapping cortical hubs in tinnitus. BMC Biol. 2009;7:80. [Full text]

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HIPPOCRATE'S OATH

"I swear by Apollo, the healer, Asclepius, Hygieia, and Panacea, and I take to witness all the gods, all the goddesses, to keep according to my ability and my judgment, the following Oath and agreement:

To consider dear to me, as my parents, him who taught me this art; to live in common with him and, if necessary, to share my goods with him; To look upon his children as my own brothers, to teach them this art.

I will prescribe regimens for the good of my patients according to my ability and my judgment and never do harm to anyone.

I will not give a lethal drug to anyone if I am asked, nor will I advise such a plan; and similarly I will not give a woman a pessaryto cause an abortion.

But I will preserve the purity of my life and my arts.

I will not cut for stone, even for patients in whom the disease is manifest; I will leave this operation to be performed by practitioners, specialists in this art.

In every house where I come I will enter only for the good of my patients, keeping myself far from all intentional ill-doing and all seduction and especially from the pleasures of love with women or with men, be they free or slaves.

All that may come to my knowledge in the exercise of my profession or in daily commerce with men, which ought not to be spread abroad, I will keep secret and will never reveal.

If I keep this oath faithfully, may I enjoy my life and practice my art, respected by all men and in all times; but if I swerve from it or violate it, may the reverse be my lot."

MAIMONIDE'S PRAYER

"Almighty God, Thou has created the human body with infinite wisdom. Ten thousand times ten thousand organs hast Thou combined in it that act unceasingly and harmoniously to preserve the whole in all its beauty the body which is the envelope of the immortal soul. They are ever acting in perfect order, agreement and accord. Yet, when the frailty of matter or the unbridling of passions deranges this order or interrupts this accord, then forces clash and the body crumbles into the primal dust from which it came. Thou sendest to man diseases as beneficent messengers to foretell approaching danger and to urge him to avert it.

"Thou has blest Thine earth, Thy rivers and Thy mountains with healing substances; they enable Thy creatures to alleviate their sufferings and to heal their illnesses. Thou hast endowed man with the wisdom to relieve the suffering of his brother, to recognize his disorders, to extract the healing substances, to discover their powers and to prepare and to apply them to suit every ill. In Thine Eternal Providence Thou hast chosen me to watch over the life and health of Thy creatures. I am now about to apply myself to the duties of my profession. Support me, Almighty God, in these great labors that they may benefit mankind, for without Thy help not even the least thing will succeed.

"Inspire me with love for my art and for Thy creatures. Do not allow thirst for profit, ambition for renown and admiration, to interfere with my profession, for these are the enemies of truth and of love for mankind and they can lead astray in the great task of attending to the welfare of Thy creatures. Preserve the strength of my body and of my soul that they ever be ready to cheerfully help and support rich and poor, good and bad, enemy as well as friend. In the sufferer let me see only the human being. Illumine my mind that it recognize what presents itself and that it may comprehend what is absent or hidden. Let it not fail to see what is visible, but do not permit it to arrogate to itself the power to see what cannot be seen, for delicate and indefinite are the bounds of the great art of caring for the lives and health of Thy creatures. Let me never be absent- minded. May no strange thoughts divert my attention at the bedside of the sick, or disturb my mind in its silent labors, for great and sacred are the thoughtful deliberations required to preserve the lives and health of Thy creatures.

"Grant that my patients have confidence in me and my art and follow my directions and my counsel. Remove from their midst all charlatans and the whole host of officious relatives and know-all nurses, cruel people who arrogantly frustrate the wisest purposes of our art and often lead Thy creatures to their death.

"Should those who are wiser than I wish to improve and instruct me, let my soul gratefully follow their guidance; for vast is the extent of our art. Should conceited fools, however, censure me, then let love for my profession steel me against them, so that I remain steadfast without regard for age, for reputation, or for honor, because surrender would bring to Thy creatures sickness and death.

"Imbue my soul with gentleness and calmness when older colleagues, proud of their age, wish to displace me or to scorn me or disdainfully to teach me. May even this be of advantage to me, for they know many things of which I am ignorant, but let not their arrogance give me pain. For they are old and old age is not master of the passions. I also hope to attain old age upon this earth, before Thee, Almighty God!

"Let me be contented in everything except in the great science of my profession. Never allow the thought to arise in me that I have attained to sufficient knowledge, but vouchsafe to me the strength, the leisure and the ambition ever to extend my knowledge. For art is great, but the mind of man is ever expanding.

"Almighty God! Thou hast chosen me in Thy mercy to watch over the life and death of Thy creatures. I now apply myself to my profession. Support me in this great task so that it may benefit mankind, for without Thy help not even the least thing will succeed."

Information for Health Professionals

Information for Patients

Modern challenged parts of the oath:

  1. To teach medicine to the sons of my teacher. In the past, medical schools gave preferential consideration to the children of physicians.
  2. To practice and prescribe to the best of my ability for the good of my patients, and to try to avoid harming them. This beneficial intention is the purpose of the physician. However, this item is still invoked in the modern discussions of euthanasia.
  3. I will not give a lethal drug to anyone if I am asked, nor will I advise such a plan. Physician organizations in most countries have strongly denounced physician participation in legal executions. However, in a small number of cases, most notably the U.S. states of Oregon,[10] Washington,[11]Montana,[12] and in the Kingdom of the Netherlands,[13] a doctor can prescribe euthanasia with the patient's consent.
  4. Similarly, I will not give a woman a pessary to cause an abortion. Since the legalization of abortion in many countries, the inclusion of the anti-abortion sentence of the Hippocratic oath has been a source of contention.
  5. To avoid violating the morals of my community. Many licensing agencies will revoke a physician's license for offending the morals of the community ("moral turpitude").
  6. I will not cut for stone, even for patients in whom the disease is manifest; I will leave this operation to be performed by practitioners, specialists in this art. The "stones" referred to are kidney stones or bladder stones, removal of which was judged too menial for physicians, and therefore was left for barbers (the forerunners of modern surgeons). Surgery was not recognized as a specialty at that time. This sentence is now interpreted as acknowledging that it is impossible for any single physician to maintain expertise in all areas. It also highlights the different historical origins of the surgeon and the physician.
  7. To keep the good of the patient as the highest priority. There may be other conflicting 'good purposes,' such as community welfare, conserving economic resources, supporting the criminal justice system, or simply making money for the physician or his employer that provide recurring challenges to physicians
http://www.worldallergy.org/educational_programs/world_allergy_forum/barcelona2008/rabe/

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