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This is a condition seen in elderly people with laxity of the l Increase in tear osmolarity. Symptomatic relief can be provided by release variety is a pellet of a cellulose compound prescribing artifcial tears 4 to 6 times a day, modifying without preservative that is inserted below the tarsus the frequency as necessary. Sometimes surgical excision of of the lower lid where it dissolves slowly providing a redundant folds (conjunctivoplasty) is required. Lateral tarsorrhaphy can longed application of silver salts (silver nitrate, proteinate, also be performed to reduce the evaporation of tears. The staining, which is l Squamous metaplasia of the ocular surface epithe most marked in the lower fornix, is due to the impregnation lium may play a part in the production of symptoms. Signs of conjunctival congestion, papillae, follicles, pattern of involvement and type of discharge help in making a clinical diagnosis. It is important to examine the entire conjunctival surface carefully including lid ever sion to look for foreign bodies and other signs. One should know how to differentiate conjunctival from circumcorneal congestion as this has important implications for correct diagnosis and treatment of different disorders. The diseases that affect the conjunctiva can be congenital, idiopathic, infectious, traumatic, iatrogenic and neoplastic. Horizontal Vertical the corneal thickness is more in the periphery than in Anterior surface 11. The substantia propria or stroma plexus from which branches travel radially to enter the 3. There are no specialized nerve endings or sensory and devoid of lymphatic channels. Due to its dense nerve supply the cornea is an extremely Oxygen supply: the metabolism of the cornea is pref sensitive structure. Oxygen is mostly derived from the tear flm portant in maintaining a healthy normal environment for with a small contribution from the limbal capillaries and the corneal epithelial cells. Transparency of cornea: the transparency of the cornea Nerve supply: the cornea is supplied by nerves which is due to: originate from the small ophthalmic division of the tri geminal nerve, mainly by the long ciliary nerves which l Its relatively dehydrated state. This relative state of dehy run in the perichoroidal space and pierce the sclera a short dration is maintained by the integrity of the hydrophobic distance posterior to the limbus. The light (arrowed) is coming from the left and in the beam of the slit-lamp the sections of the cornea and the lens are clearly evident. The epithelial cells cells is to limit the fluid intake of the cornea from the have junctional complexes which prevent the passage of tear aqueous. There are junctional complexes in the l Uniform refractive index of all the layers endothelium too, but the infux of aqueous humour into the l Uniform spacing of the collagen fibrils in the stroma. Trauma is less than the wavelength of light so that any irregu to either of these layers produces oedema of the stroma. If there is an increase in separation of the fuid from the damaged epithelium into the deeper stroma. The functions of the cornea include: the permeability of the cornea is related to the charac l Allowing transmission of light by its transparency teristics of the various components. Lipids in cell mem l Helping the eye to focus light by refraction branes have poor permeability to salts and are hydrophobic l Maintaining the structural integrity of the globe so as to help maintain the relative state of dehydration l Protecting the eye from infective organisms, noxious which is important for corneal transparency. The hydrophilic stroma has better With advancing age, the cornea becomes less transpar permeability to salts. This brings the humoral and cellular Healing/regeneration capacity: In case the cornea defence mechanisms closer to the infamed site for the sustains injury due to any cause such as trauma, infection purpose of immunological defence and repair. However, or surgery, and if the injury is superfcial involving only the the transparency is compromised by this and a corneal epithelium, the stratifed squamous epithelium covering opacity develops if the process continues. This can arise from the conjunctival superfcial vascular plexus regeneration of corneal epithelial cells is mainly from stem or the deep plexus from the anterior ciliary arteries. The cells, which are epithelial cells present as palisades of capillaries arising from these plexuses normally end as Vogt at the limbus. These mitotically active cells with an loops at the limbus, but on stimulation new vessels can increased surface area of basal cells present in folds and invade the cornea. When the stimulus is eliminated, these palisades are ideally suited for this purpose. When damaged, it does not regener heat, dry air and sand, which can all affect the ocular sur ate but is replaced by fbrous tissue, as is the stroma. Vitamin A defciency weakens ated by the endothelial cells to some extent when injured. Heredi trauma, but can develop tears or ruptures if the trauma is tary disorders, dystrophies and other degenerations can severe. The corneal endothelium does not regenerate Pathophysiology but adjacent cells slide to fll in a damaged area. The corneal epithelium and endothelium maintain a the special importance of diseases of the cornea lies in steady fuid content of the corneal stroma. Besides causing an opacity corneal diseases such as keratoconus, and kerato globus can also affect vision by altering shape and curva ture leading to a change in refractive status. Loss of epithelium is termed as epithelial defect and can which is obscure but may be due to deposition of iron be demonstrated clearly by staining with 1% sodium fuores from the pre-corneal tear film. A loss of epi scar tissue, as occurs in healing of a large sloughed corneal thelium with infammation in the surrounding cornea is called ulcer, it is called a corneoiridic scar or if ectatic, an ante a corneal ulcer. If accompanied by an outpour A thin, diffuse nebula covering the pupillary area interferes ing of leucocytes the appearance is more off-white or yellow more with vision than a strictly localized dense leucoma, so ish and this hazy area is termed as an infltration. Unlike healthy transparent corneal tissue, scar tissue many of the rays to fall upon the retina where they blur the is white and opaque in varying degrees of severity. An opacity does nature, extent, pattern and density of scarring vary accord not necessarily prevent the light from being focussed upon the ing to the nature of the original infammatory disease. There is thus a loss of brightness Corneal Opacity rather than of defnition, although this is impaired by the l Nebula or a nebular corneal opacity: If the corneal scar results in slight opacification allowing the details of the iris to be seen through the opacity. Light falling upon it is not irregularly refracted and does not pigmented line in the palpebral aperture, the nature of distort the retinal image. Chapter | 15 Diseases of the Cornea 195 superimposition of a diffuse entoptic image of the opacity whenever the endothelium has suffered damage so that upon the clear image of the external object.

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There is an excellent correlation between both examinations to locate some, but not all, capillary dilations. It is surrounded by a hyperautofuorescent area that could correspond to a leakage area. Fluorescein angiography confrms the presence of a nonhomogeneous fuorescence remote from the tumor. The fundus autofuorescence image (2) shows a central, dark nonhomogeneous image associated with a lower hyper-autofuorescence that could indicate a chronic serous retinal detachment. The late phase of the indocyanine green angiography (4) shows a central dark image, corresponding to the nevus. The B-scan pass at this level (6) confrms the presence of a serous retinal detachment. In the present case, B-scan ultrasonography has found a simple nevus complicated by leakages without signs of malignancy. On fundus autofuorescence (2), there are signifcant retinal pigment epithelium disturbances resulting in a very dark image. On the B-scan (8) passing through the macula, the deep retina appears hyper-refective. The scans passing through the choroid (B) show a localized disappearance of the choroidal circulation and choriocapillaris. Blue refectance image (2): the greyish oval is very suggestive of the diagnosis of macular telangiectasia type 2. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Spectral Domain Optical Coherence tomography angiography of choroidal neovascularization. Choroidal neovascularization analyzed on ultrahigh-speed swept-source optical coherence tomography angiography compared to spectral-domain optical coherence tomography angiography. Type 2 neovscularization secondary to age-related macular degeneration imaged by optical coherence tomography angiography. Optical coherence tomography angiography of asymptomatic neovascularization in intermediate age-related macular degeneration. Detection of non-exudative choroidal neovascularization in age-related macular degeneration with optical coherence tomography angiography. Optical coherence tomography angiography of type 1 neovascularization in age-related macular degeneration. Optical coherence tomography angiography characteristics of polypoidal choroidal vasculopathy. Optical coherence tomography angiography of idiopathic polypoidal choroidal vasculopathy. Optical coherence tomography angiography of polypoidal choroidal vasculopathy and polypoidal choroidal neovascularization. Optical coherence tomography angiography features of subretinal fbrosis in age related macular degeneration. Highlight shows a perfused vascular network within the fbrosis associated with changes in outer retinal layers and choriocapillaris in contact with fbrosis. Optical coherence tomography angiography shows signs of vascular abnormalization with antiangiogenic therapy for choroidal neovascularization. Shows vascular rearrangement under antiangiogenic treatment but there is an absence of normalization. Longitudinal optical coherence tomography angiography study of type 2 naive choroidal neovascularization early response after treatment. Characterizing the efect of anti-vascular endothelial growth factor therapy on treatment-naive choroidal neovascularization using optical coherence tomography angiography. Optical coherence tomography angiography reveals mature, tangled vascular networks in eyes with neovascular age-related macular degeneration showing resistance to geographic atrophy. Optical coherence tomography angiography of choroidal neovascularization secondary to pathologic myopia. Retinal and choroidal vasculature in birdshot chorioretinopathy analyzed using spectral domain optical coherence tomography angiography. Edema and ischemia Diabetic retinopathy and diabetic macular edema Ishibazawa A, Nagaoka T, Takahashi A, et al. Optical coherence tomography angiography in diabetic retinopathy: a prospective pilot study. Capillary plexus anomalies in diabetic retinopathy on optical coherence tomography angiography. Evaluation of preretinal neovascularization in proliferative diabetic retinopathy using optical coherence tomography angiography. Distinguishing diabetic macular edema from capillary nonperfusion using optical coherence tomography angiography. Automated quantifcation of capillary non-perfusion using optical coherence tomography angiography in diabetic retinopathy. Enlargement of foveal avascular zone in diabetic eyes evaluated by en face optical coherence tomography angiography. Optical coherence tomography angiography of the foveal avascular zone in diabetic retinopathy. This study stresses the disorganization of the vasculature surrounding the central avascular zone with the presence of more pronounced disturbances at the deep capillary plexus. Optical coherence tomography angiography in retinal vein occlusion: evaluation of superfcial and deep capillary plexa. En-face optical coherence tomography angiography of neovascularization elsewhere in hemicentral retinal vein occlusion. Optical coherence tomography angiography in retinal vascular diseases and choroidal neovascularization. Microvascular abnormalities on optical coherence tomography angiography in macular edema associated with branch retinal vein occlusion. Capillary network anomalies in branch retinal vein occlusion on optical coherence tomography angiography. Optical coherence tomography angiography shows deep capillary plexus hypo perfusion in incomplete central retinal artery occlusion. Optical coherence tomography angiography of a choroidal neovascularization in adult-onset foveomacular vitelliform dystrophy: pearls and pitfalls. Optical coherence tomography angiography in adult-onset foveomacular vitelliform dystrophy. Chronic central serous chorioretinopathy imaged by optical coherence tomographic angiography. Vascularization of irregular retinal pigment epithelial detachments in chronic central serous chorioretinopathy evaluated with oct angiography. Optical coherence tomography angiography of shallow irregular pigment epithelial detachments in pachychoroid spectrum disease. Association of choroidal neovascularization and central serous chorioretinopathy with optical coherence tomography angiography. Outer retina capillary invasion and ellipsoid zone loss in macular telangiectasia type 2 imaged by optical coherence tomography angiography. Characteristics and quantifcation of vascular changes in macular telangiectasia type 2 on optical coherence tomography angiography. Wide-feld imaging of retinal vasculature using optical coherence tomography-based microangiography provided by motion tracking. Professor Bruno Lumbroso, for his perspicacity, his communicative enthusiasm and the kindness of his welcome. All translation, adaptation and reproduction rights by any means are reserved for all countries. On one hand, the reproductions are strictly reserved for the private use of the copier and not intended for collective use, and on the other hand short anlyzes and citations are justifed by the scientifc or information of the work in which they are incorporated (Law of March 11, 1957 Art. Previous editions copyrighted 2011, 2007, 2003, 1990, 1984, 1978, 1970, 1964, 1959, 1954, 1948, 1942, 1938, 1936, 1934, 1930, 1926, 1923, 1918, 1912, 1907 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the Publisher. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treat ment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evalu ating and using any information, methods, compounds, or experiments described herein. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instruc tions, or ideas contained in the material herein. This classic textbook your information spectrum as much as we did in preparing with its unique features provides a comprehensive com it for you.

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Less common are severe refractive errors, megalocornea, cataract, uveal colobomas, and secondary glaucoma. The long bones are very fragile, fracturing easily and often healing with fibrous bony union. The very thin sclera allows the blue color imparted by the underlying uveal tract to show through. Occasionally, abnormalities such as keratoconus, megalocornea, and corneal or lenticular opacities are also present. Vogt-Koyanagi disease is characterized by bilateral uveitis, alopecia, poliosis, vitiligo, and hearing defects, usually in young adults. If there is exudative retinal detachment due to exudative choroiditis, the term Harada disease is used. There is a tendency toward recovery of visual function, but this is not always complete. The majority of cases are caused by drugs, most commonly allopurinol and carbamazepine. Whether specific treatment such as corticosteroid therapy is beneficial is uncertain. The primary ocular abnormality is membranous conjunctivitis, leading to tear deficiency due to occlusion of the lacrimal gland ducts, symblepharon, loss of goblet cells and meibomian glands, and entropion with trichiasis or ectropion. Loss of limbal stem cells exacerbates corneal disease, which may result in corneal ulceration, infection, and perforation, and panophthalmitis. Treatment includes intensive topical preservative-free lubricants and corticosteroids, release of symblepharon, amniotic membrane grafts, lid surgery, and topical antibiotics for secondary infection. The usual vectors are small ixodid ticks that have a complex three-host life cycle involving multiple mammalian and avian species. Initially, in the area of the tick bite, there develops the characteristic skin lesion of erythema chronicum migrans, often accompanied by regional lymphadenopathy, malaise, fever, headache, myalgia, and arthralgia. Several weeks to months later, there is a period of neurologic and cardiac abnormalities. Other ophthalmologic abnormalities that have been reported include uveitis, ischemic optic neuropathy, optic disk edema and neuroretinitis with macular star, bilateral keratitis, and choroiditis with exudative retinal detachments. Recommended treatment options include oral doxycycline, amoxicillin, or cefuroxime or intravenous ceftriaxone for 14 days. All patients must undergo medical assessment before treatment is started, including individual susceptibility to adverse effects; be counseled about the benefits and risks of the treatment options; and be monitored throughout the course of treatment. Commonly used drugs are corticosteroids (eg, prednisolone), azathioprine, cyclosporine, mycophenolate mofetil, and cytotoxic agents such as methotrexate and cyclophosphamide. Risk factors for central and branch retinal vein occlusion: A meta analysis of published clinical data. The propensity for immunologic disease to affect the eye derives from a number of factors, including the highly vascular nature of the uvea, the tendency for immune complexes to be deposited in various ocular tissues, and the exposure of the mucous membrane of the conjunctiva to environmental allergens. Immunologic diseases of the eye can be grossly divided into two major categories: antibody-mediated and cell-mediated diseases. As is the case in other organs, there is ample opportunity for the interaction of these two systems in the eye. The same antigen must be shown to produce an immunologic response in the eye of an experimental animal, and the pathologic changes produced in the experimental animal must be similar to those observed in the human disease. It must be possible to produce similar lesions in animals passively sensitized with serum from an affected animal upon challenge with the specific 786 antigen. Unless all of the above criteria are satisfied, the disease may be thought of as possibly antibody-dependent. In such circumstances, the disease can be regarded as antibody-mediated if only one of the following criteria is met: 1. If antibody to an antigen is present in higher quantities in the ocular fluids than in the serum (after adjustments have been made for the total amounts of immunoglobulins in each fluid). If abnormal accumulations of immunoglobulins are present at the site of the disease. If the ocular disease is associated with an inflammatory disease elsewhere in the body for which antibody dependency has been proved or strongly suggested. In severe cases, due to a compromise in the tear film, photophobia and blurred vision can be present. Immunoglobulin (Ig) E (reaginic antibody) is attached 787 to mast cells lying beneath the conjunctival epithelium. Binding of the offending antigen to corresponding IgE triggers the release of vasoactive substances, principally leukotrienes and histamine, resulting in vasodilation and chemosis. Diagnosis Diagnosis is usually clinical, but it can be confirmed by a high proportion of eosinophils in Giemsa-stained scrapings of conjunctival epithelium. Skin test with a causative allergen produces wheal and flare of an immediate (type 1) hypersensitivity response. In moderate or persistent cases, dual action topical agents consisting of both antihistamines and mast cell stabilizers are indicated. In severe or particularly persistent cases, topical steroids for short duration and dual action agents are indicated, although steroids are seldom used in practice. Allergen-specific immunotherapy can produce short and long-term improvement of symptoms and is indicated in severe, persistent cases, as well as in patients who have simultaneous rhinoconjunctivitis. Patients are dosed either sublingually or subcutaneously with gradually increasing doses of suspected allergens, with attenuation of allergen-specific type 2 T-cell response being the probable mechanism of action. There may be severe eczema of the lids and periorbital skin, and the bulbar conjunctiva is hyperemic and thickened. Papillary hypertrophy is often present in the palpebral conjunctiva, particularly inferiorly. Inflammatory mediators and thickening of the lids cause corneal damage including punctate erosions, abrasions, ulcerations, and mucous plaques. There is predisposition to herpes simplex virus keratitis, anterior and posterior subcapsular cataracts, and keratoconus. The keratinized epithelium of the papillae may cause punctate corneal erosions and a large abrasion (shield ulcer), over which a fibrin and mucus-containing plaque may form and require surgical removal. At the limbus, there may be gelatinous infiltration, which often is associated with white accumulations of eosinophils and desquamated epithelial cells (Horner-Trantas dots). There is a type 1 hypersensitivity reaction to skin testing with food extracts, pollens, and various other antigens, but the significance of these reactions is not established. In refractory cases, immunomodulators such as cyclosporine and tacrolimus may be beneficial. Ankylosing spondylitis in adults, which also affects males more frequently than females, may be accompanied by acute anterior uveitis, often with fibrin. It is triggered by gastrointestinal infection usually with Shigella, Salmonella, or Campylobacter or genitourinary infection particularly with Chlamydia. The first attack of ocular inflammation usually consists of a self-limited papillary conjunctivitis. Subsequent attacks consist of acute iridocyclitis of one or both eyes, occasionally with hypopyon. Mucous membrane (ocular cicatricial) pemphigoid is associated with antibodies to a component of conjunctival basement membrane, provably a protein of hemidesmosomes.

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Other countries have similar but varying requirement for visual acuity, visual field, and absence of diplopia. Health professionals, particularly ophthalmologists, are obligated to ensure that patients failing the relevant requirements do not drive, if necessary by informing the licensing body. Population-based studies indicate that the global prevalence of vision loss has been declining since the early 1990s, with less vision loss from infectious diseases such as trachoma but increasing vision loss from conditions related to aging, such as cataract and age-related macular degeneration. Accordingly, the majority of individuals with vision loss are older (82% over the age of 50) but also poor, with close to 90% living in low and middle-income countries. Women are at much 860 higher risk of vision loss, with population-based surveys estimating that 64% of those with vision loss worldwide are women. It is estimated that over 12 million children (between the ages of 5 and 15) with impaired vision could have normal vision with correction of refractive error alone. The leading causes of blindness are cataract, glaucoma, age-related macular degeneration, and corneal opacities. Vision loss caused by infectious diseases such as trachoma is decreasing due to improvements in public health. Causes of Worldwide Vision Loss and Blindness Causes of vision loss around the world are influenced by the level of social development and local geography. In developing countries, besides refractive error, cataract is the leading cause, with glaucoma, trachoma, leprosy, onchocerciasis, and xerophthalmia also being important. Corneal scarring is a significant cause of monocular vision loss in the developing world, accounting for 850,000 cases of blindness per year in India alone. In more developed countries, vision loss is to a great extent related to the aging process. Although cataract is still an important cause of vision loss, the leading causes of blindness in North America and other developed countries are age-related macular degeneration, diabetic retinopathy, and glaucoma. Other causes are herpes 861 simplex keratitis, retinal detachment, retinal vascular disorders, and inherited retinal degenerative disorders. Differences again exist when comparing the relative causes in developed and developing countries. The major causes in developing countries are corneal scarring, trachoma, genetic diseases, and cataract. In many parts of the developing world, the facilities available for treating cataract are grossly inadequate, being hardly sufficient to cope with new cases and completely inadequate for dealing with the backlog of existing cases, currently estimated to be 10 million. It is not fully understood why the frequency of cataract varies so greatly in different geographic areas, although exposure to ultraviolet radiation and recurrent episodes of dehydration, often occurring in severe diarrheal diseases, are thought to be important. With decreasing mortality rates and changing demographics, age-related causes of vision loss, including cataract, are expected to continue to rise. Although no current medical treatments exist to delay the development of cataract, it is estimated that a 10-year delay in cataract formation would reduce the number of individuals requiring surgery by 45%. Until an effective treatment that can prevent or delay cataract formation is devised, it will remain a leading cause of vision loss and will become an increasingly important global public health concern. Uncorrected Refractive Error Uncorrected refractive error is clearly avoidable through the provision of 862 corrective lenses; however, this remains a major cause of vision loss throughout the world, even in developed countries such as the United States, but particularly in developing countries where limited access to eye care professionals, low prevalence of eye health-seeking behavior, and low affordability of corrective lenses remain major problems. Glaucoma the incidence of vision loss due to glaucoma has decreased in recent years as a result of earlier detection, improved medical and surgical treatment, and a greater awareness and understanding of the disorder. However, in many developing countries, glaucoma remains a common cause of vision loss. This is especially the case in West Africa, where untreated open-angle glaucoma is extremely common. In China and Southeast Asia, there appears to be a preponderance of narrow-angle glaucoma. Approximately 3 million individuals worldwide are blind due to glaucoma, and a simple easy method of detecting patients at risk still does not exist. Treatment is also a major problem because of the poor compliance of most patients for taking daily eye drops. A simple but safe surgical procedure may ultimately be the only solution for reducing the needless burden of vision loss from this disease. Trachoma Trachoma causes bilateral keratoconjunctivitis, generally in childhood, which leads in adulthood to corneal scarring that, when severe, causes vision loss. About 40 million people have trachoma, most of them in Africa, the Middle East, and Asia. It can be treated with various antibiotics, including tetracyclines and erythromycin, but azithromycin is proving to be the drug of choice. The number of individuals who are blind from trachoma has dropped from 6 million to 1. Prevention of spread of infection will require provision of proper sanitary facilities, including clean water for drinking and washing, waste disposal, fly control, and behavioral change in hygiene. Onchocerciasis 863 Onchocerciasis is transmitted by bites of the blackfly, which breeds in clear running streams. It is endemic in the greater part of tropical Africa and Central and South America. The most heavily infested zone is the Volta River basin, which extends over parts of Dahomey, Ghana, Ivory Coast, Mali, Niger, Togo, and Upper Volta. The major ophthalmic manifestations of onchocerciasis are keratitis, uveitis, retinochoroiditis, and optic atrophy. The disease is prevented by insect eradication and personal protection by screening. Treatment with ivermectin is extremely effective in killing the microfilaria and sterilizing the adult females residing in nodules in the body. The effect of the mass distribution of ivermectin in areas where onchocerciasis is endemic is a public health success story. Like leprosy, onchocerciasis is definitely decreasing in its importance as a worldwide cause of vision loss because of successful treatment programs. Other Causes Age-related macular degeneration, diabetic retinopathy, and corneal disorders are discussed elsewhere (see Chapters 6, 10, and 15). Although prevention is a logical approach to the solution of many problems in all branches of medicine, in practice, there are a number of hurdles to overcome. For any particular condition, it is essential that individuals at risk be easily identified. If their identification requires population screening, the process should be easy to perform, accurate, and reliable. Preventive measures must be both effective and acceptable to the target population. Legislation may be required for certain measures but may engender resentment when it is felt to infringe on personal liberty. The successes that have been achieved in occupational health are an example of what can be accomplished if a consensus of opinion is established. In ophthalmology, the major avenues for preventive medicine are ocular injuries and infections, genetic and systemic diseases with ocular involvement, and ocular diseases in which the early treatable stages are often unrecognized or ignored. Injuries can vary from closed globe (blunt trauma or chemical injuries) to open globe injuries including rupture, perforation, and penetration (see Chapter 19). Occupational Injuries Eye injuries remain a significant risk to worker health, especially among individuals in jobs requiring intensive manual labor. Grinding or drilling commonly propels small fragments of metal into the environment at high velocity, and these projectiles can easily lodge on the cornea or penetrate the globe through the cornea or sclera. Tools with sharp ends are also commonly involved in producing penetrating ocular injuries.

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Used in gonorrhea and inflammations of urinary and respiratory tracts after subsidence of acute stage. Copper is a great oxygen carrier and is thought to favorably influence the hemoglobin when given in minute amounts, supplying oxygen and, as Grauvogl said, "neutralizing an overplus of iodosmone in the blood. Apart from this, copper influences spasmodic affections and nausea and vomiting resulting reflexly from the absorption of ptomaines and organic poisons. Precipitated metallic copper, in minute doses triturated with sugar, is sometimes used to get the uncombined ac tion of copper, but Cupric acetate acts in a similar manner. Its indications are diarrhea, with large and frequent discharges and accompanied by watery vomiting, colic, green and offensive stools, It is valuable in cholera infantum in frequent doses of 1-1000 gr. Very enthusiastic reports are appearing favoring it as an improvement over digitalis in the treatment of heart disease. Pharmacopceia drops crude carbolic acid, calls purified carbolic acid "Phenol," and makes official "CresoL" the heavy oil of coal tar, which distils over at from 325 to 3750 Fahr. Crude carbolic acid is a very complex substance, containing "Phenol" and three isomeric cresols, hydrocarbons, and water. For many uses as a disinfectant it is just as serviceable and is much more economical than "Cresol. It is much more expensive than crude carbolic acid, and is to be preferred in surgical work. All of these agents are of much greater bactericidal power than phenol, and they are rapidly displacing it in surgery. Creosote is used in phthisis of a non-febrile character, sympathetic vomiting (in small doses), chronic bronchitis, fetid diarrhea. While cresol or "coal-tar creosote" can be used internally, it is so apt to contain the toxic elements in excess that the safe plan is to use only beechwood creosote. Even this sometimes contains coerulignol, and only re liable makes should be used. Also used in gleet, catarrh of the bladder, and in some bronchial affections with free secretion. There are two remedies known by this name: Cucurbita citrulills, or the ordinary watermelon (the seeds being employed), is quite markedly diuretic. The infusion of the seeds is a most excellent non-irritating diuretic, valuable in the diseases of children who cry during urination, and who stain the diapers a deep color. Only preparations of the fresh root carry the full activity of this drug, although the fluid-extract and oleoresin are of some value. This rather feeble agent finds its greatest field of usefulness in cerebral hyperemia and functional nervousness of infants and in mild convulsive affections due to teething or to irritation of the brain in scrofulous children. With those children who are wakeful at night and yet are not ill and want to laugh and play, it is a very satisfactory drug. It will frequently take the place of an opiate and is not apt to do any harm, but it must be remembered that it is not a remedy for pain and its influence is in func tional diseases, not in organic affections. It is of some service in the case of adults who suffer from nervousness, restlessness, and hyperesthesia induced by genito-urinary diseases, but is not to be depended upon in severe cases. There is no scientific evidence in favor of the claim that it possesses marked aphrodisiac properties. A full consideration of this important drug will not be attempted here, but a few views will be pre sented. If given in the way this little book advocates the administration of many remedies, viz. If larger doses are given six to ten hours apart and not too long continued, there is no more reliable remedy as a heart stimulant. Heart stimulants should not be used for every trifle, but in prostration, surgical shock, in the crisis of debilitating disease, to slow a rapid and feeble pulse in sthenic fever with high temperature, compressible pulse and vital failure, the failing heart of pneumonia, cyanosis, impending death from mitral disease, failure of heart in child-birth, these and many more serious conditions are promptly met with digitalis in free doses of the tincture or fluidextract. Do not combine with other heart stimulants or follow the dose with food or water or bulky medication. If the other heart stimulants are needed and are specifically indicated, each in its place, give the one indicated and reserve digitalis. The average dose of the infusion is 2 teaspoonfuls, and I K doses should not be given initially except where urgently demanded. A poultice of digitalis leaves applied directly over the kidneys will manifest the diuretic action in a short time. This antispasmodic and anodyne is usually incorporated in the formulae of "female regulators. It is especially useful in bilious colic and the pain of muscular spasm in the intestines. Spasmodic affections of the pelvic viscera and after-pains come within its sphere of action. An active diuretic recommended in dropsy and nephritis, especially that following scarlet fever. Drosera is antispasmodic, expectorant, and a respiratory sedative; highly useful in dry, irritable cough of a hoarse, resonant, and spasmodic nature. In my experience it is, generally speaking, the best agent we have in whooping cough. Spasmodic dry coughs generally are much relieved by it, and especially the cough of measles. It is much stronger than atropine, and is sometimes employed hypodermically in mental diseases. Homeopathic ophthalmologists use the 3x dilution of Duboisia, or corkwood tree, in the treatment of conjunctivitis, hyperemia of the retina, and for pain over the eyes. Personally, I have had no experience in its homeopathic employment, but from its resemblance to belladonna, which we know relieves capillary hyperemia in small doses, it is reasonable to expect results of a similar nature from this more active drug. In large doses narcotic, producing so many disagreeable symptoms as to be almost abandoned as a narcotic drug. Its physiologic action is quite complicated, and it is hard to work out its action in small doses. Employed in the treatment of cutaneous eruptions, particularly of a scaly nature; also in chronic rheumatism and chronic catarrh. It has a specific relation also to the skin, glands, and digestive organs, mucous membranes secreting more profusely while the skin is inactive. The rheumatic troubles induced by damp cold are aggravated by every cold change and somewhat relieved by moving about. Now for an eclectic view of dulcamara in small doses: "Dulcamara is a remedy for all conditions resulting from suppression of secretion from exposure to cold and dampness. Any one studying materia medica in this way will soon discover little reason for a divided profession. Several firms make excellent fluidextracts, but by far the best preparation is a purified, decolorized, and assayed fluidextract given the trade name of Echafolta. Echinacea mildly irritates the terminal nerve endings, causes a feeling of constriction of the throat, promotes the flow of saliva, is diaphoretic and diuretic, stimulates the glandular organs, actively stimulates secretion and excretion, retrograde tissue metabolism, the lymphatic system, and the hematogenic processes. It does not appear to possess active toxic properties, bu: is somewhat sedative to the nervous system in large doses. This agent is used by all three schools in exactly the same doses and indications. It corrects blood depravation (so far as a drug can) when due to auto-infection of an acute type, progressive blood taints due to non-elimination or the slow development of toxins, tendencies to sepsis or non traumatic gangrene, foul discharges and depraved states of the secretions, and morbid puerperal discharges. Naturally, this action is less marked and cannot be exercised quickly enough to be of any material advantage in most instances. It has long been the dream of therapeutists to get an antiseptic into the blood that would kill bacteria and not kill the patient. In introducing echinacea the most effective step in this direction thus far has been taken, and I have hopes that its principles will be isolated and be made suitable for hypodermic injection as we employ diphtheria. As an intestinal antiseptic, echinacea takes first rank, and I firmly believe it to be of the most positive use in the initial stages of typhoid fever. In the eclectic wards of Cook County Hospital, Chicago, it has been carefully studied in this connection, and is much relied upon.

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Coronal magnetic resonance imaging of bilateral acoustic neuromas in neurofibromatosis type 2. A subgroup of patients with nerves having a thickened nerve core and a low-density perineural proliferation are more likely to be symptomatic. Epiretinal membranes, combined pigment epithelial and retinal hamartomas, optic disk gliomas, and optic nerve sheath meningiomas occur with increased frequency. Other manifestations are cerebellar hemangioblastoma; cysts of the kidneys, pancreas, and epididymis; pheochromocytoma; and renal cell carcinoma. In the peripheral retina, it initially manifests as dilation and tortuosity of retinal vessels, followed by development of an angiomatous lesion with hemorrhages and exudates. A stage of massive exudation, retinal detachment, and secondary glaucoma occurs later and will cause blindness if left untreated. Among all patients with retinal capillary hemangioma, about 80% have von Hippel-Lindau disease, and they usually have multiple lesions. Among patients with solitary retinal capillary hemangioma, the prevalence of von Hippel-Lindau disease is about 45%. The diagnosis is usually obvious by personal or family history but may become apparent after screening for associated lesions or after genetic testing. Sporadic retinal capillary hemangioma not associated with von Hippel-Lindau disease usually presents in the fourth decade. Treatment & Prognosis Retinal capillary hemangiomas may be treated with laser photocoagulation, cryotherapy, or plaque radiotherapy. All patients, particularly those with von Hippel-Lindau disease, need regular screening for detection of new lesions. Patients with von Hippel-Lindau disease also need regular screening for development of central nervous system and abdominal disease. Presymptomatic detection of the lesions of von Hippel-Lindau disease greatly improves the prognosis. First-degree relatives of patients with von Hippel-Lindau disease also need to undergo regular screening. Genetic testing increasingly allows identification of individuals specifically at risk. There is corresponding angiomatous involvement (leptomeningeal angiodysplasia) of the meninges and brain, which causes seizures (85%), mental retardation (60%), and cerebral atrophy. Since the cortical lesions calcify, they can be seen on plain skull x-rays after infancy. Unilateral infantile glaucoma on the affected side frequently develops if there is extensive involvement of the conjunctiva with hemangioma of the episclera and anterior chamber anomalies. Lid or conjunctival involvement nearly always implies ultimate intraocular involvement and glaucoma. Forty percent of patients with a port wine stain on the face develop choroidal hemangioma, usually diffuse rather than circumscribed, on the same side. Choroidal hemangioma may require treatment with laser photocoagulation or radiotherapy. Large, tortuous, dilated vessels covering extensive areas of the retina are an important diagnostic clue and can cause cystic retinal degeneration with decreased vision. All signs and symptoms are progressive with time, but the ataxia appears first as the child begins to walk, and the telangiectases appear between 4 and 7 years of age. The recurrent infections relate to thymic deficiencies and corresponding T-cell abnormalities as well as to deficiency of immunoglobulins. Saccadic and eventually pursuit abnormalities produce a supranuclear ophthalmoplegia. Adenoma sebaceum (angiofibromas) occurs in 90% of patients over the age of 4 years, and the number of lesions increases with puberty. Subependymal nodules in the periventricular areas of the brain can calcify and appear as candle-wax gutterings or drippings on radiologic studies. The prognosis for life relates to the degree of central nervous system involvement. In severe cases, death can occur in the second or third decade; if there is minimal central nervous system involvement, life expectancy should be normal. Clinical manifestations occur as a critical level of intraneuronal lipid deposition is reached, resulting in a progressive disease, including dementia, visual disturbance, and neuromotor deterioration. A halo occurs from loss of transparency of the ganglion cell ring of the macula, which accentuates the central red of the normal choroidal vasculature. Retinal degeneration without a macular cherry-red spot occurs in mucopolysaccharidoses and in the lipopigment storage disorder, neuronal ceroid lipofuscinosis. Acute nonarteritic anterior ischemic optic neuropathy and exposure to phosphodiesterase type 5 inhibitors. Nowhere else in the body can a microcirculatory system be visualized directly and investigated with such precision or neural tissue be examined so easily, and nowhere else are the results of minute focal lesions so devastating. Many systemic diseases involve the eyes, and therapy demands some knowledge of the vascular, rheologic, and immunologic nature of these diseases. The first branches of the ophthalmic artery are the central retinal artery and the long posterior ciliary arteries. The retina is supplied by the retinal and choroidal circulations that have contrasting anatomic and physiologic characteristics. They function as end arteries and feed a capillary bed consisting of small capillaries (7 m) with tight endothelial junctions, which forms the blood-retina barrier, and they are autoregulated, there being no autonomic nerve fibers. Examination of the retinal vessels is facilitated by red-free light and fluorescein angiography, whereas indocyanine green angiography highlights the choroidal vessels. They usually indicate abnormality of the retinal or choroidal vascular system, but they may be caused by any condition that alters the efficacy of the endothelial barrier. Pallid swelling of small optic disk with hemorrhages (A) with small optic disk also in the other eye (B). Fluorescein angiogram shows reduced perfusion of a segment of the optic disk (filled arrow) and the adjacent choroid (unfilled arrow) in the early phase (C) and leakage in the late phase (D). Impairment of blood supply to the optic disk produces sudden visual loss, usually with an altitudinal field defect, and sectoral pallid swelling of the optic disk, sometimes with hemorrhages. Pathologic studies show infarction of the retrolaminar region of the optic nerve, which is supplied by the short posterior ciliary vessels that are part of the choroidal circulation. Fluorescein angiography demonstrates reduced perfusion of the disk and adjacent choroid; dilation of the 721 capillaries, which are part of the retinal circulation, on the surface of its unaffected portion; and late leakage. Hypertension and arteriosclerotic disease are the commonly identified additional factors in middle age, although it is uncertain whether vascular occlusion or a reduced arterial pressure is the precipitating event. With increasing likelihood with increasing age over 50 years, optic disk infarction may be caused by giant cell arteritis. Bilateral optic disk infarction can be seen after sudden hypotension following acute blood loss, but posterior (retrobulbar) optic nerve infarction without optic disk changes in the acute stage is more typical.

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Obstructive azoospermia due to congenital absence of the vas Tract Disease deferens Chronic i. Paradoxically, genotypes associated with otherwise mild phenotypic effects have the greater risk for causing pancreatitis; compared with genotypes associated with moderate to severe disease phenotypes. Careful interpretation of sweat chloride values and repeated testing may be necessary. How useful is fecal pancreatic elastase 1 as a marker of exocrine pancreatic disease. Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice. The cystic fibrosis transmembrane conductance regulator gene and ion channel 86 Acute Pancreatitis function in patients with idiopathic pancreatitis. Canadian Cystic Fibrosis Patient Data Registry Report 2008, In: Cystic Fibrosis Canada, 08. Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers. Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice. Longitudinal evaluation of serum trypsinogen measurement in pancreatic-insufficient and pancreatic-sufficient patients with cystic fibrosis. Genotype analysis and phenotypic manifestations of children with intermediate sweat chloride test results. Cystic fibrosis birth rates in Canada: a decreasing trend since the onset of genetic testing. Age-related alterations of immunoreactive pancreatic cationic trypsinogen in sera from cystic fibrosis patients with and without pancreatic insufficiency. Genotype and phenotype correlations in patients with cystic fibrosis and pancreatitis. Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. A test for concentration of electrolytes in sweat in cystic fibrosis of the pancreas utilizing pilocarpine by iontophoresis. Laboratory standards and guidelines for population-based cystic fibrosis carrier screening. Variation in a repeat sequence determines whether a common variant of the cystic fibrosis transmembrane conductance regulator gene is pathogenic or benign. A novel mutation in the cystic fibrosis gene in patients with pulmonary disease but normal sweat chloride concentrations. Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test. Diseases of Infancy and Childhood, In: Robbins and Cotran Pathologic Basis of Disease (7th ed. Genotype-phenotype correlation and frequency of the 3199del6 cystic fibrosis mutation among I148T carriers: Results from a collaborative study. Pathology of cystic fibrosis: review of the literature and comparison with 146 autopsied cases. Towards the ideal quantitative pancreatic function test: analysis of test variable that influence validity. Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program. Mutations in the cystic fibrosis transmembrane regulator gene and in vivo transepithelial potentials. Introduction About a decade ago, a question was raised about glyburide, a widely used sulfonylurea, as a possible cause for acute pancreatitis (Blomgren). Since then, several systemic reviews reveal the incidence of acute pancreatitis in patients with type 2 diabetes 1. Five years after the concern was raised about glyburide and soon after the first of the incretin based, exenatide, had gained a significant market share, reports of pancreatitis again began to surface. Examination of two different insurance data bases, again reveal no real increase over other agents used to treat type 2 diabetes. This chapter will cover the wide variety of drugs that have been associated with acute pancreatitis as well as the studies that substantiate increase in acute pancreatitis in type 2 diabetes. The rate of acute pancreatits in incretin based agents and other agents as mentioned above seems the same as the rate in the population of type 2 diabetic as a whole. Background In 2002 Blomgren reported the association of acute pancreatitis with obesity and glyburide therapy in type 2 diabetic subjects (Blomgren). The first of a new class of incretin-mimetic agents, exendatide (Byetta) was introduced for the treatment of diabetes in 2005 and by 2006 the first report of acute pancreatitis was made by Denker (Denker) and soon others began to immerge. Perhaps, the fact that the pathway involved with each of these new types of agents has the potential to affect the gastrointestinal tract, there was concern that this might be responsible for precipitating acute pancreatitis. Diabetic comorbidities of hypertriglyceridemia and obesity may increase their risk for acute pancreatitis. New etiologies continue to be described as evidenced by the report by Frulloni and colleagues of an autoimmune pancreatitis identified by a novel antibody directed at an epitope homologous to a protein from Helicobacter pylori (Frulloni). Type 2 diabetes is associated with obesity and hyperlipidemia, each of which has been considered a risk factor for pancreatitis (Trivedi, Blomgren). Many drugs have been associated with acute pancreatitis, yet these include drugs from varied classes, with very different modes of action and metabolic degradation pathways without any uniform explanation. Only alcohol, which both stimulates exocrine pancreatic secretion and contraction of the outlet sphincter (of Oddi) can be explained. In a 2005 review, Trivedi reported that, of the top 100 prescribed drugs in the United States, 44 have been associated with acute pancreatitis (Trivedi). These include over the-counter agents such as acetaminophen, common antibiotics such as trimethoprim/ sulfamethoxazole and erythromycin, commonly used agents such as furosamide, glucocortiods, statins, angiotensin conversion inhibitors as well as agents used to treat human immunodeficiency virus acquired immunodeficiency syndrome, and oncologic agents. Diabetes and acute pancreatitis the association of diabetes and acute pancreatitis was noticed at least a century ago and reported by Korte (Korte). Schumacker also noted cholelithiasis and/or cholecystitis in patients with acute pancreatitis. Gall bladder disease is known to be increased in diabetes as well as a cause for acute pancreatitis (Pagliarulo). Warren made a similar case for pancreatitis causing diabetes in five cases (Warren 1950). Warren reported acute pancreatitis in 12 patients 6 months to 13 years after the diagnosis of diabetes in a pathology text dealing with pathology of diabetes (Warren 1952). Root reported 5 cases of acute pncreatitis with diabetes, four of which were shown at autopsy to have fatty livers, which suggests type 2 diabetes with accompanying insulin resistance (Root). She noted 3 cases of acute Diabetes or Diabetes Drugs: A Cause for Acute Pancreatitis 93 pancreatitis in hospitalized patients with previously diagnosed diabetes which prompted an examination of the records of 103 patients admitted to Mount Sinai Hospital, New York City between 1936 and 1954. She found 5 more cases of acute pancreatitis in patients with pre existing diabetes. Again, these observations were made in an era prior to any anti-diabetic therapies other than insulin. As more recent reports of acute pancreatitis have been published in association with agents used to treat diabetes, the earlier association of acute pancreatitis in the diabetic patient has not been acknowledged. Since these early twentieth century reports have been primarily in the way of case reports of acute pancreatitis in subjects with diabetes on a particular agent used in the treatment of diabetes or its comorbidities. The only series is that by Blomgren suggesting glyburide could increase the risk of acute pancreatitis and the relationship of that agent and the other agents has been primarily circumstantial (Balani, Blomgren, Jeandidier, Singh). The most common etiologies of acute pancreatitis accounting for 70-80% of cases are alcohol and gallstones. Chapman reported in 1996 a higher prevalence of gallstone disease based on ultrasound examination or report of cholecystectomy in diabetics (32. Common Agents used in treating diabetic patients with reports of acute pancreatitis the increased prevalence of gall bladder disease in subjects with diabetes has been addressed more recently in the medical literature than the association with acute pancreatitis.

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Synthetic oil of wintergreen has been prepared and synthetic salicylic acid purporting to be true acid has been made from it. This is a fraud upon the part of the maker that has vastly complicated the already much involved therapy of salicylic acid. A conservative view of the matter makes it appear that the natural acid produces less irritation than does the synthetic, is eliminated more rapidly, and has a more regular and reliable influence where the temperature is elevated. Salicylic acid produces tinnitus, a reduction of reflex action, depression of cerebration, reduces temperature, is diaphoretic and antiseptic, and is apt to irritate the kidneys. The unaltered acid is employed in ulcerations and cancerous conditions of the stomach and in foul breath and offensive expectoration. Sodium salicylate is usually preferred for internal administration in rheumatism, sciatica, lumbago, and for its supposedly alterative properties. In small doses salicylic acid is employed in tonsilitis, giving I or 2 grains every two hours. It is highly efficient where there is a septic influence or the follicles of the tonsils are involved. Externally, salicylic acid is used in the treatment of indolent ulcers, cold abscesses, chilblains, pruritus, and many skin affections. Since aconite contains aconitine, pseudo-aconitine, aconine, pseudo-aconine, picraconitine, and aconitic acid, it is readily seen that no alkaloid really represents the full therapeutic range of aconite. It is too dangerous a drug to employ in doses verging upon the toxic, and especial care should be exercised when the fluidextract or the stronger tinctures are employed. Large medicinal doses, according to Bartholow, produce gastric pain and nausea, reduce the number and force of the heart beats, and lower arterial tension; there is increased action of the skin and kidneys, some muscular weakness, and sometimes diarrhea or vomiting. These large doses are seldom employed except where muscular spasm accompanies sthenic febrile states. He suggests its employment, broadly, in the early stages of all acute inflammations, and externally as an anodyne application. It is useful in capillary engorgement, and especially so if alternated with small dose of belladonna. In acute congestions, nervous palpitations, the first stage of enteritis with fever, myalgia, otitis, suppression of menses from cold, and catarrhal inflammations of mucous membranes generally, it is a remedy for which we have no real substitute. It is recommended in dyspnea, in nicotine poisoning, and chronic diffuse nephritis. The logical outcome is that this very energetic remedy, or adonidin, should be very carefully employed. Personal experience has taught the present author to depend upon this drug to give prompt results where indicated, and also to produce great discomfort when administered to persons having only temporary functional heart disturbances. In small doses this agent has acted remarkably well in my hands in cases of venous engorgement and weak heart giving rise to varicose ulcers. Both of these substances demand careful and detailed study in order to intelligently employ them internally. Its surgical and special uses are many, but it is principally employed in hay fever ("adrenalin inhalant") and in iritis, conjunctivitis, and inflammations of the tonsils and larynx in solution (as chloride) in I to 10,000 or I to 1000 of solvent. Its internal administration should not be lightly entered upon, but it is valuable if used strictly within its indications. Its tonic action is upon the cerebro-spinal system, but it is inferior to nux vomica in this regard. It acts upon the portal circulation and lessens the caliber of the rectal capillaries, thus favorably influencing hemorrhoids, and more especially the large dry locally. Aesculus glabra, or Ohio Buckeye, is a more toxic agent than the above-described remedy, more profoundly exerting its influence upon the nervous system. Its uses are similar, but it is to be preferred only when the action is to be directed deeper than the rectum; consequently, in congestions of the uterus and of the portal system it is of service in many cases. Regular physicians have never appreciated Aesculus for the very tangible reason that nearly all fluidextracts have been made from the dried bark, whereas it is the nut or fruit that is active. The faint, anti-periodic properties possessed by the bark are of very little moment. In the popular mind, buckeye has long been esteemed in the treatment of rheumatism. Really, it has very little influence upon true rheumatism, but will relieve the backache affecting the sacrum and hips caused by portal congestion or by being upon the feet too much. In small doses it has long enjoyed some reputation in the gastro-intestinal catarrh of bottle-fed babies. It ap pears to act best when the trouble is incidental to irritation of the nervous system. While it cannot be regarded as a thoroughly reliable remedy, and without antiseptics in alternation with it usually dismally fails, yet it appears that I I doses of the first decimal dilution in alternation with 1-1000 grain doses of arsenite of copper is a fairly efficient treatment. In large doses ailanthus depresses the functions of the brain and spinal cord, and its only successful employment in such doses is to expel tapeworm. It does well in alternation with whatever medication is demanded, but it does not combine well with other drugs except the bitter tonics. This drug was at one time much employed in regular practice, and it is worthy of more general employment now, especially since recent investigation has shown its real activity to reside in a volatile oil dissipated almost entirely in the preparations usually employed. It is with regret that we are unable to commend its fluidextract, since regular physicians naturally prefer to use drugs obtained from non-sectarian sources. It is one of a class of remedies roughly classed together and usually pre scribed in a hit or miss fashion. This should not be, and we will endeavor to give in this volume the definite indications for these agents separately. Aletris should be employed in anemic and relaxed conditions in the female pelvis associated with poor digestion. Eliminating all hypothetical matter, this tincture has been found of real value in the colds of vocalists in which the greatest annoyance is experienced upon entering a warm room. Useful in portal congestions and the troubles of phlegmatic beer drinkers and persons who overload themselves with starchy food and sweets. In still smaller doses it will often relieve a sense of insecurity in the rectum, but quite as often fails to do so. Owing to its ammonia base, it is especially applicable when a nerve sedative is indicated in asthenic conditions. In febrile conditions with feebleness it is a stimulating diaphoretic, used in small and frequent doses in scarlet fever, measles, and erysipelas. Catarrhs of all kinds are amenable to its influence, the dose depending upon the amount and character of the exudate. The fresh infusion is of somewhat uncertain value in vomiting and "morning sickness. For adults the dose must be much larger, but it is very much open to question whether hydrocyanic acid in safe doses really possesses much sedative influence upon the walls of the stomach. Used in angina pectoris, spasmodic asthma, epilepsy, syncope, dyspnea, and in poisoning by cocaine. Full doses act upon the nerve centers, increasing reflexes, and hence large doses should not be given to nervous patients. The agent is a very promising one, and is worthy of employment in angina pectoris, dyspnea, and in cardiac feebleness. This is a good remedy for men under stress of business who lose sleep and smoke to excess, become irritable, have lapses of memory, and become worse as soon as they close the eyes and try to sleep. In these cases give I to 3 drop doses every hour or two and 5 drops when retiring. It should seldom be employed in its first two indications, since it is very depressing. It relieves capillary bronchitis, especially in children, who should have minute doses freqeuntly repeated. In adults, when the bronchi are loaded with mucus that is raised with difficulty, it is an efficient remedy. Oft times gives rise to prostrating sweats, and is exceedingly erratic in its influence. Fortunately, its toxic influences are readily overcome by the use of brandy, strychnine, and heat. The utmost of conservatism should govern its administration, and one should bear in mind its many incompatibles. It is a definite stearoptine of considerable value, whereas the so-called "liquid apiol" is an alcoholic extract of the parsley fruit.

References:

  • https://students.umw.edu/healthcenter/files/2011/08/Aphthous-Ulcers.pdf
  • http://www.nhlbi.nih.gov/files/docs/guidelines/03_sec2_def.pdf
  • https://dhss.delaware.gov/dph/dcr/files/dcrhospreporting.pdf

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