Anke Hemmerling MD, PhD, MPH

• Director, Interdisciplinary MPH Program

https://publichealth.berkeley.edu/people/anke-hemmerling/

There is usually rapid ulceration and perforation of corneal which eventually leads to blindness if treatment is delayed erectile dysfunction doctors in maine purchase viagra with fluoxetine visa. Thorough examination of the eyes by a pediatric eye specialist is needed to guide the management of the patients erectile dysfunction young buy viagra with fluoxetine 100/60 mg with amex, so refer all children to Paediatric Eye Tertiary Centre whey protein causes erectile dysfunction viagra with fluoxetine 100/60 mg with visa. These affect the exposed area of conjunctiva as a response to chronic dryness and exposure to sunlight impotence causes cheap viagra with fluoxetine 100/60 mg visa. Treatment Treatment for pterygium is surgical excision in advanced stage where the visual axis is involved erectile dysfunction in your 20s generic viagra with fluoxetine 100/60 mg without a prescription. Surgery should be done by qualified eye care personnel and antibiotic steroid combination drops should be given postoperative erectile dysfunction icd 9 code 2012 purchase 100/60 mg viagra with fluoxetine mastercard. Treatment If tumour is suspected, Excise the mass with wider margin (2 mm) Treat the margins with Mitomycin C, 5 Fluorouracil or cryotherapy Send the specimen for histological examination For advanced tumours where the globe has been infiltrated, removal of the eye is indicated (Enucleation or exenteration) Send patients with confirmed diagnosis to Oncologist for radiotherapy 4. Diagnosis 200 P a g e the most common initial sign is white pupil reflex (leokocoria), followed by squint, and rarelyvitreous haemorraghe, hyphema, ocular/periocular inflammation, glaucoma and in late stagesproptosis and hypopyon. Management the goals of treatments are: To save the patients life To savage the patients eye and vision if possible Choice of treatment depends on Size of tumor, Location and Extent of the tumour. Postnatal age >7 days: 1200-2000 g: 15 mg/kg/day in divided doses every 12 hours >2000 g: 30 mg/kg/day in divided doses every 12 hours For anaerobic infections: 204 P a g e A: Metronidazole Oral, I. The manifestations of brain abscess initially tend to be nonspecific, resulting in a delay in establishing the diagnosis. Cryptococcal antigen test should be done as there are cases of negative Indian ink results with cryptococcal meningitis. Diagnosis Early or prodromal clinical features of the disease include apprehensiveness, restlessness, fever, malaise and headache the late features of the disease are excessive motor activity and agitation, confusion, hallucinations, excessive salivation, convulsions and hydrophobia Note: Death is considered as invariable outcome. In addition, patients should receive rabies immune globulin with the first dose (day 0) Tetanus toxoid vaccine see section on Tetanus 208 P a g e 1. It afflicts 5% of the population and is characteristically a disorder of young adults and affects women twice as often as men. Acute anxiety attacks are characterized by sudden onset of tension, restlessness, tremors, breathlessness, tachycardia and palpitations. Diagnosis Diagnosed after recurrent (several) panic attacks within a one month period. M half hourly in 2 hours to a maxmum of 20mg/24 hours till acute attack is controlled. Such mood may be associated with increased energy/activity, talkativeness and a reduction in the need for sleep and features may be accompanied by grandiose and/or religiose delusions. Adjunct treatment Antiparkinsonian drugs should only be used if extrapyramidal side effects occur or at higher doses of antipsychotics likely to cause extrapyramidal side effects. Any of the following can be used: C: Trihexyphenidyl (Benzhexol 5mg once to two times a day (O) last dose before 1400 hours S: Procyclidine 10mg two times a day last dose before 1400 hours Referral First psychotic episode Poor social support High suicidal risk or risk of harm to others Children and adolescents the elderly Pregnant and lactating women No response to treatment Intolerance to medicine treatment Concurrent medical or other psychiatric illness Epilepsy with psychosis 2. For Acute dystonic reaction Usually follows administration of dopamine-antagonistic drug. If seizures persist, increase phenytoin by 50 mg increment to a maximum dose of 600 mg daily If no appreciable improvement, change to carbamazepine, stopping phenytoin by reducing dose by 50 mg per week. Increase the dose to maximum If possible the combination of these drugs should be avoided 215 P a g e Patients still having seizures despite of having the above drugs should be referred to a higher level of treatment. V) 15 ml (1ml/min) as a bolus Give anticonvulsant: A: Diazepam 5 mg/minute (slow I. Alcohol Dependence Syndrome Alcoholism is a syndrome consisting of two phases: problem drinking and alcohol addiction. Problem-drinking is the repetitive use of alcohol, often to alleviate tension or solve other emotional problems. Diagnosis Predominantly visual hallucinations Disorientation Agitation Tachycardia Hypertension A low-grade fever may be present Withdrawal tonic-clonic seizures may occur between24 and 48 hours following cessation of alcohol intake Note: It is important to consider alternative causes, when making the diagnosis. Transient worsening of condition may be due to metabolic disorders, infections and drug side effects. It is also recommended that, for diabetics a snack should be taken before and after playing sport. No Yes Step 3: Oral Continue to monitor therapy Combination Add another class of oral agents. Continue to monitor No Step 5: Insulin More than once daily insulin therapy in a therapy required: Either Refer the patients to secondary conventional or intensive secondary or or tertiary care tertiary service 2. Screen for complication that may affect surgical risk: Nephropathy, cardiac disease, proliferative retinopathy. Insulin Dilutions A solution of Soluble Insulin 1 unit / ml made up in Normal Saline. Primary Causes: Iodine deficiency Congenital Drugs; Iodine excess (contrasts media containing iodine), lithium, antithyroid drugs, p aminosalisylic acid, interferon alfa and other cytokines, aminoglutethimide. Enlargement of the thyroid gland may result in normal increased, or decreased hormone secretion. Post thyroidectomy Iodine should be given daily indefinitely to prevent recurrence, following dosing schedule give above Physiological doses of iodine can be given even in pregnancy. It is actually necessary to provide the therapy to avoid iodine deficiency to the foetus Patients should continue taking iodized salt indefinitely (Ref. It is usually due to diffuse hyperplasia and hypertrophy of the thyroid gland (Graves disease). Maintenance dose 5mg for up to one year Toxic Nodular Goitre Can be treated with antithyroid drugs and surgery or radio-iodine C: Carbimazole 40mg (O) once daily for 3 weeks then 20mg daily for 3 weeks. Iron deficiency anaemia A: Ferrous sulphate200 mg (O) every 8 hours Children5 mg/kg body weight every 8 hours. Pyruvate kinase deficiency c) Haemoglobin -Abnormal haemoglobin such as HbS, C, Unstable Hb Clinical features the disease may occur at any age and sex Patient may present with symptom and features of Anaemia Symptoms are usually slow in onset however rapidly developing anaemia can occur Splenomegaly is common but no always observed Jaundice Treatment i. Immunosuppressive drugs for the patients who fail to respond to corticosteroids and splenectomy. It is important to distinguish between painful crises and pain caused by another process Aplastic crises occurs when erythropoiesis is suppressed Sequestration crises occurs in children or occasional in adult with an enlarged spleen due to massive pooling of red cells in the spleen Treatment Guidelines Nonspecific measures A: Folic acid 5mg once daily Specific measures S: Hydroxyurea 15mg/kg/day. Frequent spontaneous haemarthrosis factor is needed several times Moderate 2-5%of normal 1Haemorrhage secondary 0. Patients present with a history of easy bruising, menorrhagea, gum bleeding and spontaneous joint bleeding in severe form. Clinical feature for adult thrombocytopenia appears to be more common in young women than in young men but amoung older patients, the sex incidence may be equal. Most adult patient presents with a long history of purpura, menorrhagia, epistaxis and gingival haemorrhage. Paralysis may be associated, often been brought by improper transfer of the patient to the hospital. Thus lion, tiger, leopard, hyena, bear, elephant, hippopotamus, buffalo, wolf and wild pig are examples of the wild animals that have bitten man. Symptoms:Most bites and stings result in pain, swelling, redness, and itching to the affected area Treatment and Management Treatment depends on the type of reaction Cleanse the area with soap and water to remove contaminated particlesleft behind by some insects Refrain from scratching because this may cause the skin to break down and an infection to form Treat itching at the site of the bite with antihistamine Give appropriate analgesics Where there is an anaphylactic reaction treat according to guideline. Decision of treatment for the uterine carcinoma is best done in hospital under specialist care. Decision of treatment for the vulvo-vaginal carcinoma is best done in hospital under specialist care. Regional/zonal or tertiary depending on treatment expertise Treatment: Predominantly surgical. Radiotherapy: Post operative radiotherapy is indicated for high risk recurrence (positive 265 P a g e margins and nodal involvement). Decision of treatment for malignant trophoblastic tumours is best done in hospital under specialist care. Referral: All patients must be referred to a gynecologist for evaluation and decision on mode of treatment. If total tumour removal is not possible, then maximum debulking (cyto-reductive) surgery should be done. Chemotherapy Adjuvant chemotherapy: Is indicated for all unfavourable histologies as well as advanced stages. The most common warning sign of skin cancer is a change in the appearance on exposed areas of the skin, such as a new growth or a sore that will not heal. Surgery: the aim of sugery is total local excision where possible; wide local excision and graft; amputation sometimes is required. Radiotherapy: Indication: Positive margin, high grade disease or inoperable tumour. Chemotherapy: S: Topical 5 fluorouracil for very superficial lesions or carcinoma in situ. Detection/Prevention: Frequent self-check or screening exercise and prompt treatment of early keratotic changes. Important aetiological factors include excessive intake of tobacco either by smoking or chewing and alcohol intake (particularly spirits). Decisions of treatment for head and neck tumours are best discussed at Tumour board. Tumour present as goiter and can remain silent for decades without any discomfort. Clinical features: Presence of a thyroid mass or scar, laryngeal nerve palsy, hoarseness, dyspnoea, dysphagia. Treatment Radioactive iodine ablation Further thyroxine replacement therapy (for life). Dilatation with or without intubation should always be considered to ensure continued ability to swallow. Look for pallor, weight loss, supraclavicular foss nodes, abdominal and rectal examination, epigastric mass, hepatomegally, periumbilical nodes. Surgery: Total or partial gastrectomy, bypass with or without tumour removal eg gastrojejunostomy. There is a strong association of this cancer and hepatitis B infection and/or alcohol consumption. Anatomic extent of involvement: A: One lobe only; B: Two lobes; C: Metastatic disease; D: Cirrhosis. Early stages may be superior to surgery in the sense that sphincter function is preserved. This may be visible to the naked eye gross hematuria or detectable only by microscope. Other possible symptoms include: Dysuria or increased frequency and bilharzia exposure, weight loss and anaemia. Treatment: Surgery: Total cystectomy is mutilating and causes poor quality of life. Bilateral orchidectomy is a surgical procedure which aims at surgical castration Hormonal therapy: May be given as the sole treatment for patients deemed unfit for surgery. Alternatively hormonal therapy is used as adjunct to other treatments with the intention of reducing the chance of local recurrence or metastatic disease. Palliative radiotherapy is valuable to bone metastases, massive haematuria, spinal cord compression, pathological fracture, etc as indicated. Clinical features: Peripheral lymph node enlargement (commonest site neck 281 P a g e Hepatomegally and/or splenomegally in advanced stages. B symptoms (weight loss, night sweats, and fever), pruritus, alcohol induced pain, general condition, throat, lymphnodes (site, number, size, consistency, mobility, matting), respiratory system, abdomen (liver, spleen, other masses), bone tenderness. Clinical feature: May first be noticed as a painless swelling of the facial bone or jaw which is typical presentation in equatorial Africa setting. Referral: Urgent referral to a specialized centre Treatment: Combined modality approach: Surgery: Is for early disease or organ preservation. Treatment: Aim: Cure Surgery: Lesions amenable to wide excision without causing severe functional disabilities are resected. If parasites are found second line treatment should be started and treatment failure recorded. In Tanzania the commonest presentations of severe malaria are severe anaemia and coma (cerebral Malaria). Taking and reporting of blood smear must not be allowed to delay treatment unduly. In the event that an artesunate suppository is expelled from the rectum within 30 min of insertion, a second suppository should be inserted and, especially in young children, the buttocks should be held together for 10 min to ensure retention of the rectal dose of artesunate. Dosage regimen: Give single dose of 10mg of quinine salt per kg bodyweight (not exceeding a maximum dose of 600mg). The solution is 60mg/ml artesunate o Dilute with 5ml of 5% dextrose or dextrose/saline. Infusions should be discontinued as soon as the patient is able to take oral medication.

Superior Limbic Keratoconjunctivitis Clinical features Photophobia erectile dysfunction lubricant buy discount viagra with fluoxetine 100/60mg line, watering and mild Marked injection of the superior limbus and the ocular discomfort are common presenting symp upper palpebral conjunctiva and the presence of toms erectile dysfunction treatment by food order viagra with fluoxetine with visa. Punctate punctate keratitis in the upper half of the cornea epithelial lesions stain with fluorescein but the characterize superior limbic keratoconjunctivitis subepithelial lesions do not impotence hypertension viagra with fluoxetine 100/60 mg on-line. Here the Clinical features Ocular discomfort erectile dysfunction causes ppt buy 100/60 mg viagra with fluoxetine free shipping, irritation and use of acyclovir is beneficial erectile dysfunction pills natural cheap viagra with fluoxetine master card. Frequent instillations mild lacrimation are common presenting symp of tear substitutes give relief in dry eye syndrome erectile dysfunction pump implant video purchase viagra with fluoxetine 100/60 mg line. Mechanical denuding Filamentary Keratitis of the corneal epithelium or cauterization may be necessary. The use of a bland ointment or Filamentary keratitis is characterized by the hypertonic saline drops (5%) or ointment (6%) with presence of mucous filaments associated with pressure bandage may promote healing. Lamellar Etiology It is found in patients with kerato keratoplasty or bandage contact lens is helpful in conjunctivitis sicca, recurrent corneal erosions, indolent cases. Photophthalmia Clinical features the filament comprises a mucous Etiology Photophthalmia may be caused by core surrounded by the corneal epithelium. The exposure to short wavelength ultraviolet rays one end of the filament is attached to the either reflected from snow surface (snow epithelium while the other moves freely over the blindness) or from other sources (welding or short cornea. The closure of the lids or eye movements circuiting of high-tension electric current). The put tension on the filaments causing pain and essential pathology is the desquamation of corneal foreign body sensation. Treatment the condition is treated by instillation of hypertonic saline (5%) and manual removal of Clinical features Photophthalmia is characterized filaments and short-term patching of the eye. The by photophobia, blepharospasm, burning and use of topical 10-20 % acetyl cysteine benefits the watering. Corneal Erosions Treatment Prophylactic wearing of dark glasses Etiology Punctate epithelial erosions of the cornea is advisable. Once the condition develops, which stain with fluorescein are found in acute antibiotic ointment, cycloplegic drop and semi blepharoconjunctivitis. Viral Keratitis the condition may be familial or associated with trauma or corneal dystrophy. The corneal erosion Herpes Simplex Keratitis is a serious disorder and occurs due to a defect in the word with herpes is derived from a Greek word the basement membrane of the corneal epithelium. In the epithelial layers are loose and prone to fact, it is a misnomer since the disease spreads by separation and frequent erosions. Recurrent erosions often occur in the lower part Etiology the disease is caused by herpes simplex of the cornea. The former affects the upper part of the body, mostly the mouth, lips and eyes while the latter attacks essentially the ano-genital region. The infection is quite common, 50-90% of all human beings may suffer from herpes during their life-time. An attack does not produce lasting immunity as recurrences are frequent, particularly associated with upper respiratory tract infection. The incidence of herpetic use of corticosteroids and other immunosup infection increases with age. The recurrent infection remains subclinical in approximately infection is not associated with systemic features. Clinical features the clinical features of recurrent Clinical features the primary infection may take a herpetic infection of the cornea vary largely. The start with minimal symptoms of a foreign body disease may cause mild fever, malaise and regional sensation, watering and mild photophobia. When the face is involved, accompanied corneal hypoesthesia often causes skin lesions consisting of vesicles develop on the the patient to delay the medical consultation. A transient Epithelial lesions: Foreign body sensation, epithelial punctate keratitis may be found in discomfort in light, redness and blurred vision nearly 50% cases of herpetic blepharocon are common symptoms. However, a coarse epithelial punctate lesion of herpes simplex recurrent infection is the keratitis may be the forerunner of a typical herpetic dendritic ulcer (Figs 12. The primary her vesicles in the epithelium arranged in a dendritic petic infection is usually self-limiting, majority of or stellate pattern. Desquamation gives a linear branching ulcer which stains with Recurrent Infection fluorescein, while virus laden cells at the margin During the primary infection herpes virus reaches take rose bengal stain. Corneal sensitivity is the trigeminal ganglion where it may lie dormant usually diminished. Metaherpetic lesions: Recurrent corneal erosions Marked impairment of vision, mild discomfort and in herpetic infection are not uncommon. Disciform karatitis lesions are referred to as trophic or metaherpetic is characterized by a more or less central disciform keratitis. They are not caused by edema of the cornea involving stroma as well as reactivation of the virus, but represent a persistent epithelium. The margins of seen, but a ring of infiltrates (Wessely ring) may be erosions do not stain with rose bengal. The presence of keratic precipitates and reduced corneal sensation is helpful in differen tiating herpetic disciform keratitis from corneal hydrops. Stromal necrotizing keratitis is an uncommon lesion caused by active invasion and destruction of corneal stroma by herpes virus. Complications Herpes simplex keratitis may pro gress and cause vascularization. However, recurrent infections, parti needed in the management of metaherpetic cularly the stromal, pose serious therapeutic keratitis. The 3% ointment form of the drug acyclovir (800 mg 5 times a day for 2-3 weeks) is is applied 5 times daily for 2 weeks. Recent studies preferred in disciform keratitis and necrotizing have shown that acyclovir-resistant strains of herpetic stromal keratitis. However, the role of oral herpes simplex can be effectively treated by acyclovir in preventing recurrences is question ganciclovir gel (0. The symptoms, especially the pain, diminishes within Etiology the disease is caused by varicella zoster two to three days after the appearance of crops of virus. It is believed that the virus remains dormant vesicles on one side of the forehead and the scalp. The micus is an acute hemorrhagic necrotizing eye is almost always affected if the vesicles appear gasserian ganglionitis. Varicella zoster virus lies latent infiltrates, nummular keratitis and single or in sensory neural ganglion following the primary multiple microdendrites. An endogenous reactivation of latent zoster are smaller without central ulceration and virus occurs in elderly persons without any terminal bulbs, while that of herpes simplex have predisposing cause. Later, they Vaccinia can cause superficial dendritic or form crusts and leave behind pitted scars in about geographical ulceration or a severe keratitis. The affected area including Topical and systemic vaccinia immunoglo the cornea is insensitive. There keratopathy, a very serious complication of the is some evidence to suggest that vidarabine disease, may develop. Scleritis and iridocyclitis monohydrate and interferon may accelerate with multiple small keratic precipitates are not healing. However, in the early stage of the Protozoal Keratitis disease the ocular tension may be low. Sector iris Acanthamoeba Keratitis atrophy, focal choroiditis, occlusive retinal vasculitis, anterior segment ischemia and retinal Acanthamoeba keratitis is an uncommon protozoal detachment may develop. Rarely encephalitis shaped infiltrate surrounding a central corneal ulcer may supervene. The organism can Treatment Antiviral therapy should be started adhere to the contact lens surface or may be present within 72 hours of the onset of skin lesions of in nonsterile contact lens solution. Currently oral famciclovir 500 mg 3 times a day, valacyclovir 1 g Clinical features Severe ocular pain, photophobia, 3 times a day or acyclovir 800 mg 5 times a day for foggy vision and watering are common symp 7 to 10 days are recommended. Early lesion of Acanthamoeba keratitis acyclovir should be preferred in immunocom promised patients. Administration of oral corticosteroids reduces pain, prevents massive crust formation and facilitates early recovery. Enlarged corneal nerves, called radial Traumatic keratitis is described in the chapter on perineuritis, limbitis and nodular or diffuse scleritis Injuries to the Eye. Later, suppurative ulceration of the cornea or stromal abscess associated with anterior Keratitis Secondary to uveitis and hypopyon may supervene. Phlyctenular Keratitis A history of soft contact lens wear or swimming Cornea is often involved in phlyctenular kerato in contaminated water, the characteristic clinical conjunctivitis. Sometimes, phlyctens are located picture and demonstration of Acanthamoeba cysts on the cornea and appear as gray nodules slightly on direct examination of corneal scrapings raised above the corneal surface. Occasionally, a prominent leash of blood Hydrogen peroxide and chlorhexidine solution vessels grows into the floor of the phlyctenular can eradicate the organism from the contact lens. The ulcer remains 1 week, then taper over 2-3 months, propamidine superficial and seldom perforates. A sectorial superficial dendritic phlyc tenular pannus is not infrequent and usually causes intense photophobia and blepharospasm. The treatment of phlyctenular keratitis is same as that of phlyctenular conjunctivitis. Vernal Keratitis Vernal keratoconjunctivitis can involve the cornea and produce several types of lesions such as. It may range from the corneal lesions respond to the usual mild desiccation to suppuration of the cornea treatment of vernal keratoconjunctivitis. Treatment the condition can be managed by fre Neurotrophic Keratopathy quent instillations of tear substitutes in day time (Neurotrophic Corneal Ulcer) and application of eye ointment at night. If corneal Etiology Neurotrophic keratopathy results from ulcer develops, routine treatment of ulcer should a damage to the trigeminal nerve which supplies be administered. The loss of neural Rosacea Keratitis reflex leads to hydration and exfoliation of the Etiology A chronic recalcitrant keratitis is often epithelial cells. The common causes of the nerve Clinical features Rosacea is a chronic skin disease damage are herpes simplex viral infection, herpes characterized by butterfly-like erythema of cheeks zoster ophthalmicus, leprosy and injection of and nose associated with telangiectasia, hyper alcohol in the gasserian ganglion for the treatment trophy of sebaceous glands, corneal infiltrates and of trigeminal neuralgia. Rosacea keratitis is usually associated with acneform lesions of the face and Clinical features the patient remains symptom-free. There is absence of pain and lacrimation in spite of the patient complains of irritation and mild the presence of ciliary injection and multiple redness of the eyes. The cornea appears dull and interpalpebral region are dilated and small gray exfoliated. There occurs a complete loss of corneal nodules appear near the limbus which may ulcerate sensation. Other corneal Treatment the management of neurotrophic ulcer lesions include map-dot subepithelial opacities, includes frequent instillations of artificial tears, punctate epithelial keratopathy involving the lower antibiotic and atropine ointments and protection two-thirds, recurrent epithelial erosions and of the eye either by pad and bandage or bandage thinning of the cornea. Treatment the treatment of rosacea keratitis is Keratitis Lagophthalmos unsatisfactory. The keratitis should be treated on (Exposure Keratitis) the lines of phlyctenular lesions. Topical cortico steroids and systemic tetracycline (250 mg) four Etiology Nonclosure or incomplete closure of the times a day for one month and then once daily for palpebral aperture by lids, when eyes are shut, six months or doxycyclin (100 mg) twice daily for results in exposure keratitis. The regression occurs slowly, Interstitial keratitis is a parenchymatous inflam the corneal edema disappears and the vessels start mation of the cornea, more often of allergic origin, obliterating. However, ghost vessels remain wherein the corneal stroma is secondarily involved throughout the life as fine lines despite the due to a primary anterior uveitis. It may also be seen in acquired syphilis, Clinical features Syphilitic or leutic interstitial tuberculosis, sarcoidosis, leprosy, trachoma, Lyme keratitis often follows an injury or an operation disease, mumps, brucellosis, trypanosomiasis, on the eye. The disease is begins in the periphery and involves the upper usually bilateral (80%) and affects the children part of the cornea initially. The is almost always affected as evidenced by the cornea assumes a typical ground glass appearance presence of keratic precipitates. Treponema pallidum is not seen Florid stage: A dense infiltration and vasculari in the cornea even during the acute phase. In the initial phase, cellular infiltration appears the vascular growth begins at the periphery and in the deeper layers of the cornea just anterior to remains sectorial. The characteristic cell is arranged in a brush-like fashion and look dull lymphocyte. The corneal superficial conjunctival vessels are congested but lamellae get separated and undergo necrosis. However, there while, blood vessels from the limbus grow in a occurs an epaulette-like heaping of the conjunctiva brush-like manner and invade the deeper layers of at the limbus. The cornea shows a few deep Refractory cases often need more energetic opacities and empty or ghost vessels. If the cornea treatment with subconjunctival or sub-Tenon does not clear up within 18 months, the visual injections of corticosteroids. Children with interstitial keratitis may have Systemic corticosteroids should always be nonocular signs of syphilis. Stigmata of congenital combined with antisyphilitic or antitubercular syphilis include frontal prominence, depressed therapy. Tuberculous Interstitial Keratitis Keratitis Profunda Tuberculous interstitial keratitis. It affects almost same as found in the syphilitic interstitial adults and is often unilateral and may be keratitis. Clinical features Pain, photophobia, lacrimation Treatment Both local and systemic treatment and diminution of vision are usual symptoms. The opacity clears Treatment Topical cycloplegics and cortico from the center towards the periphery of the cornea steroids improve the condition. Disciform Keratitis Treatment Timely treatment of scleritis helps in Disciform keratitis is characterized by the resolution of sclerosing keratitis.

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Communication between visits will enrich the care plan produced by both the doctor and the patient. Recent Research Stories the following is a list of blog posts telling the stories about some of our recent research projects. They are building on what they learned from earlier Arthritis Foundation-funded studies. Lomas, a registered nurse, is an active volunteer and advocate for the Arthritis Foundation. Callahan is a professor at the University of North Carolina at Chapel Hill School of Medicine. Petri is the director of the Hopkins Lupus Center and professor of medicine at Johns Hopkins University in Baltimore. Thanks also to the members of the advocacy staff who contributed to the creation of State Facts: Stephanie Livingston, consumer health specialist; Julie Eller, manager of grassroots advocacy; Vincent Pacileo, director of federal affairs; and Ben Chandhok, senior director of state legislative affairs. Additionally, our thanks go to the other senior leadership team members who made this document a reality: Cindy McDaniel, senior vice president of consumer health and impact; Melissa Honabach, senior vice president of marketing, communications, and e-commerce; and Ann McNamara, senior vice president of revenue strategy. Our data regarding maintenance of efcacy and percentage of discontinuation were in line with the existing literature. In particular, over the last 20 years many advances allowed drugs to actually modify the natural history of rheumatic diseases such as Rheumatoid Arthritis, SpondyloArthritis (including Ankylosing Spondylitis), Psoriatic Arthritis, Reactive Arthritis, and more recently Systemic Lupus Erythematosus, thanks to their efectiveness in reducing disease activity, joint pain, swelling and damage progression. Biologics are derived from living cells crossing a complex biotechnological process. The intrinsic nature of these proteins makes it almost impossible to replicate an exact copy (generic) of a biological drug; therefore, biosimilars are products similar to the original drug in the active substance, but not identical for diferences in 1Department of General and Specialistic Medicine, Rheumatology Unit, Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino, Turin, Italy. However, despite the considerable saving, such shifs to biosimilar drugs are still being debated, principally over their ethical implications. Since the drugs are similar but not identical, the main issues are related to the adverse events and the lack of efcacy, which cannot be excluded. This also implies that biosimilars could theoretically work better than originators, but the variability in efectiveness for a single patient remains an unpredictable datum before efecting the switch. Despite the fact that extrapolation of indications are debated (especially for the treatment of infammatory bowel diseases since the mechanisms of action might difer from indications22), the use of biosimilars appears to be regulated worldwide by local guidelines if safety and efectiveness are demonstrated in clinical trials for at least one indication. Other data showed that the cost saved by switching patients to biosimilars could enable more efcient alloca tions of health system resources thus improving patient care. Moreover, the switch is an incentive for the originator pharmaceutical companies not only in reducing prices but also to invest in researching and developing new drugs21,34. Terefore, this shif is not to be made by pharmacists or by others in order to prevent an automatic substitution10,35. A Dutch study on 192 patients showed the highest percentage of discontinu ation (24%); a sub-analysis of its data verifed that the interruption was mainly related to subjective features such as tender joints and patient global assessment rather than objective variables. This phenomenon could be due to a nocebo efect43,47 and would require further investigations. As soon as this decree is issued, each Italian region inductees an auction for the award of a public contract between the diferent producers; the winner of this auction is then permitted to sell their drug in the aforementioned region. The prescription of biosimilars is highly recom mended for naive patients that require a specifc target therapy, whilst the switch from originators to biosimilars is encouraged for all the patients treated with the originator; however, some peculiar exceptions are established: patients with history of allergy and/or particularly hypersensitive skin, of-label prescriptions, psychological reasons, active disease that requires a diferent treatment in the short term, paediatric patients, pregnancy52,53. Considering that no changes in clinical outcomes were expected, and according to Regional recommenda tions, we properly discussed about these elements with every patient. As suggested by a Regional document, patients of-label, pregnancy and paediatric, patients with history of allergy, patients not in remis sion nor in low disease activity, patients with psychological reasons that forbid a change were excluded. At the time of the switch, every patient was informed about biosimilar properties, literature data and the possibility to return to originator if necessary. Sample analysis was stratifed by age, sex, duration of disease and concomitant therapy. Descriptive statistics will be provided for the clinical and laboratory demographic characteristics of the cases. In order to evaluate the presence of statistically signifcant diferences between the parameters considered, the 2 test for parametric variables was used. All the performed tests were bilateral and the level of signifcance was set at 5% (with a 95% confdence interval). Results 87/107 patients were included (37 male, 50 female) with a median age of 63. Data analysis showed there are no signifcant diferences in clinimetric parameters afer the switch from originator drugs to biosimilars. Discussion Biosimilars drugs are similar to the originator in terms of quality, safety and efectiveness but there are many open questions about ethical implications. Terefore, further expensive trials could be avoided to demonstrate an already existing knowledge. In the latter, access to expensive drugs is limited so the automatic substitution is in some cases allowed, and in many other cases regulated by the law60. The aim of the documents was to provide health professionals and patients clear and validated information about biosimilars, including the role of biosimilars in the economic sustainability of the National Health Service. Even if the fnal decision about the switch is entrusted to the physician (afer a Scientific RepoRtS (2020) 10:16178 doi. The analysis of our real-life data in those patients who agreed to switch, confrms what has already emerged from clinical trials and real-world data in the literature. However, this descriptive study has some limitations since it includes no data about pharmacokinetics or evalu ation of anti-drug antibodies, from neither the originator nor the biosimilar. So, it can be concluded that there is an equal balance of negative and positive aspects that make this data loss less signifcant. In conclusion, in our population, no diference has been observed with regard to efcacy and safety afer the switch from originator to biosimilar, and no predictors of non-response to switch therapy are currently highlighted. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins. Guideline on similar biological medicinal products containing biotechnology-derived proteins as active substance: non-clinical and clinical issues. Information and Submission Requirements for Biosimilar Biologic Drugs seb-pbu-2016-eng. Commissioning framework for biological medicines (including biosimilar medicines). Biological therapy in infammatory rheumatic diseases: Issues in Central and Eastern European countries. What pricing and reimbursement policies to use for of-patent biologicals in Europe Systematic switch from innovator infiximab to biosimilar infiximab in infammatory chronic diseases in daily clinical practice: The experience of Cochin University Hospital, Paris, France. Subjective complaints as the main reason for biosimilar discontinuation afer open-label transition from reference infiximab to biosimilar infiximab. Biosimilarity and interchangeability: Principles and evidence: A systematic review. Switching reference medicines to biosimilars: A systematic literature review of clinical outcomes. To switch or not to switch: Results of a nationwide guideline of mandatory switching from originator to bio similar etanercept. Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases. Biosimilars for the management of infammatory bowel diseases: Economic considerations. Switching from reference to biosimilar products: An overview of the European approach and real-world experience so far. Considerations in Demonstrating Interchangeability With a Reference Product Guidance for Industry. Switch from infiximab to infiximab biosimilar: Efcacy and safety in a cohort of patients with diferent rheumatic diseases. Long-term safety and efcacy of biosimilar infiximab among patients with infammatory arthritis switched from reference product. Additional information Correspondence and requests for materials should be addressed to M. Disease mechanisms involve local and Accepted 3 January 2012 systemic chronic in ammatory processes. A subset of these psoriasis patients will also and, in subsets of patients, pustular or guttate plaques and nail 22 13 develop psoriatic arthritis, a seronegative spondyloarthropathy and joint involvement [5,7]. In psoriasis and psoriatic arthritis, a dysregulation of psoriasis and psoriatic arthritis, long-term treatment is often 24 15 multiple pro-in ammatory and anti-in ammatory mediators required [8]. In the skin, feedback 118 53 prevent excessive trafficking of leukocytes, allowing for resolution loops involving keratinocytes, broblasts, and endothelial cells 119 54 of in ammation. Resolution of an acute in ammatory response contribute to tissue reorganization, marked by endothelial-cell 120 5555 within the local tissues and a re-establishment of immunological proliferation and deposition of extracellular matrix [12]. Skin is an blood vessel and lymphatic vessel areas are increased in psoriatic 122 57 important site for antigen presentation, and epidermal Langerhans skin lesions compared with non-involved skin, which accounts for 123 58 cells and dermal dendritic cells play pivotal roles in T cell lesion redness [23]. Angiogenic markers, such as vascular 124 59 mediated immune responses to antigens encountered in skin. In one study, 126 61 signaling pathways and anti-in ammatory signaling pathways, subjects with psoriatic arthritis had higher circulating concentra 127 62 maintaining the homeostatic functioning of the skin immune tions of Dikkopf-1 and macrophage-colony stimulating factor (two 128 63 system [11]. Instead, such agents are antibodies or compounds that 136 73 keratinocytes and myeloid dendritic cells to affect pro-in amma selectively bind with receptors or proteins on extracellular 137 74 tory processes [12]. In lesional of targeted cell types, cell-to-cell interactions, and immune 139 76 skin from subjects with psoriasis, in ammatory myeloid dendritic signaling [5]. The downstream from pro-in ammatory changes in gene transcrip 142 79 myeloid dendritic cell/T cell interaction is central to the evolution tion. To interrupt the in ammatory cascade at an earlier point, 143 80 of psoriasis [12]. T cells respond to myeloid dendritic cell antigen researchers have begun to explore modulation of intracellular 144 81 presentation by proliferating and differentiating into type 1 helper signaling that controls in ammatory-mediator gene expression. Apremilast in vitro pharmacology and activity in nonclinical 215 189 investigators. The in ammatory process in psoriasisandarthritisresultsfromaninterplaybetweeninnateimmunecells(dendriticcells,macrophages, andneutrophils),adaptiveimmunecells(Tcells),andevennon immunecells(keratinocytes, synovial broblasts,andchondrocytes). The decreased in ammatory response may lead to lower levels of in ltration by other immune cells, as well as reduced activation and proliferation of keratinocytes and synoviocytes. Together, this may lead to decreased epidermal thickening in psoriasis and decreased synovial damage in arthritis. Other apremilast mechanisms of action, such as direct effects on keratinocytes and synoviocytes, may also occur (see Table 1). Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Theeffects of apremilast onarange of effects of apremilast on several aspects of the psoriatic response, 278 246 pro-in ammatory responses in a variety of cell types also have including inhibition of reduced in ammatory responses of toll-like 279 247 been examined [55]. Histopathological examinationof theaffectedjoints inthe behavioral correlate of emesis in mice [64]. In the ferret, 363 299 brane, pannus formation, cartilage disruption hyaline cartilage apremilast inhibited lipopolysaccharide-induced lung neutrophi 364 300 destruction, and subchondral bone destruction [56]. Furthermore, while 369369 305 agent cyclosporine A inhibited all cytokines and chemokines with apremilast reduced zymosan-induced polymorphonuclear pro 370 306 greater potency than apremilast. A summary of the effects of apremilast on various cell moderate to severe psoriasis.

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Whereas it is well docu fructose-6-phosphate analog, and does not diffuse mented that increases in blood flow and glucose out of the cells in significant amounts. The magnitude of these changes these tracers relies on the labeling of the compounds in signal intensity relative to the resting conditions is with short-lived cyclotron-produced radioisotopes. Pseudocolor-coded tomographic properties of hemoglobin depending on the blood images of the radioactivity distribution are then oxygen level. Typical in-plane resolution (full width at half-maximum) is Motor and somatosensory deficits <5 mm; 3D data accumulation and reconstruction Motor function may be impaired by damage to a permits imaging of the brain in any selected plane widely distributed network, involving multiple cor or view. This means that mainly the different studies extremely difficult, and might help 50 amount of deoxyhemoglobin in small blood vessels explain the lack of a clear concept of neuronal plas is recorded, which depends on the flow of well ticity applicable to recovery from motor stroke Chapter 3: Neuroradiology Figure 3. Brain activity for hand grip compared to rest for individual subjects with corticospinal damage. A recent review con suggesting an improved functional brain reorganiza cluded that motor recovery after stroke depends on tion in the bilateral sensory and motor systems [20]. The areas included mechanisms appearing even late in the course frontal and parietal cortices, and sometimes the basal (Figure 3. These results suggest that sensorimotor learned movements after focal cortical injury are functions are represented in extended, variable, represented over larger cortical territories, an effect probably parallel processing, bilateral networks [19]. It is of importance that the unaffected hemi undamaged hemisphere can be observed, ipsilateral sphere actually inhibits the generation of a voluntary activation of motor cortex is consistently found to be movement by the paretic hand [23]. Reco unaffected hand (as in normal subjects) were accom very from infarction is also accompanied by sub panied mainly by activation of the contralateral cere stantial changes in the activity of the proprioceptive bral cortex. In addition to stronger intensity, the systems of the paretic and non-paretic limb, reflecting spatial extent of activation in motor cortex was an interhemispheric shift of attention to propriocep enlarged, and activation on the ipsilateral side was tive stimuli associated with recovery [25]. These results indicate that recruitment of ipsilateral cortices During recovery from hemiparesis, a dynamic bi plays a role in recovery. Overactivation in the primary and secondary motor area in five patients compared with normal controls 7 and 31 weeks after left capsular stroke during right thumb-index tapping. Decrease of initial bilateral overactivation to activation restricted to the primary sensorimotor cortex in the affected and primary motor cortex in the unaffected hemisphere. That the quality of recovery is mainly hemisphere caused by the lesion and contralateral dependent on undamaged portions of the language hemisphere caused by functional deactivation (dia network in the left hemisphere and to a lesser extent schisis) (review in [26]). In right-handed individuals on homologous right hemisphere areas [28] can be with language dominance in the left hemisphere, the deduced from an activation study in the course after left temporo-parietal region, in particular the angular post-stroke aphasia [29]. In patients with gyrus of both sides and in the lower part of the central aphasia attributable to purely subcortical strokes gyrus of the left side, and by less than 5% in the left deactivation of temporo-parietal cortex is regularly Broca area. This test procedure was applied to found, which is probably responsible for the aphasic 23 aphasic patients grouped according to the site of symptoms. Therefore, metabolism in the showed different patterns of activation in the acute hemisphere outside the infarct was significantly less and chronic phase, and their improvement was differ in patients with a poor outcome of post-stroke apha ent: whereas subcortical and frontal infarcts improved sia than in those with good language recovery, indi considerably in several tests, temporal infarcts cating significant cell loss caused by the ischemic showed only little improvement. In addition, the in improvement of speech deficits were reflected in functionality of the network was reduced in patients different patterns of activation in the course after with an eventual poor outcome; during task perfor stroke (Figure 3. Activation patterns in patients with left hemispheric stroke 2 and 8 weeks after stroke. In the case of subcortical and frontal infarction, the left temporal areas are reactivated correlating to better recovery of language function. This right hemisphere over-activation may in a Cochrane Review [34], improved performance in represent a maladaptive strategy and can be inter aphasia tests for spontaneous speech, which was preted as a result of decreased transcallosal inhibition reflected in increased activation in the left temporal due to damage of the specialized and lateralized gyrus, the triangular part of the left inferior frontal speech areas. Effect of repetitive transcranial magnetic stimulation on activation pattern by verb generation. This the activation studies in the course of recovery approach might open a new therapeutic strategy for of post-stroke aphasia suggest various mechanisms post-stroke aphasia. Best, even complete, recovery can only be achieved by restoration of the original activation pattern after small brain damage outside primary centers. Chapter Summary If primary functional centers are damaged, reduction of collateral inhibition leads to activation of areas around the lesion the visualization of disturbed interaction in func (intrahemispheric compensation). The role of activation in the the resting condition, and color-coded maps can be right hemisphere for residual language performance analyzed or correlated to morphological images. Functional imaging correlates from hemiparesis, a dynamic bihemispheric reorgani of recovery after stroke in humans. Repairing the human brain after stroke: inhibition can be reduced by repetitive transcranial I. The (14 C)-deoxyglucose Studies of glucose metabolism in aphasia after stroke method for the measurement of local cerebral glucose have shown metabolic disturbances in the ipsilateral utilization: theory, procedure, and normal values in the hemisphere caused by the lesion and contralateral conscious and anesthetized albino rat. Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, predominantly activated structures in the ipsilateral Ido T, et al. Estimation of local cerebral glucose utilization by positron emission tomography of [18F]2-fluoro-2 Activation studies in the course of recovery of post deoxy-D-glucose: a critical appraisal of optimization 55 stroke aphasia suggest various mechanisms for the procedures. Shimizu T, Hosaki A, Hino T, Sato M, Komori T, flow and oxygen metabolism in man using 15 O and Hirai S, et al. Motor cortical disinhibition in the positron emission tomography: theory, procedure, and unaffected hemisphere after unilateral cortical stroke. Brain oxygen utilization measured with O-15 Changes in proprioceptive systems activity during radiotracers and positron emission tomography. Brain recovery from aphasia: lesion effect or function magnetic resonance imaging with contrast dependent recruitment Speech and language Arm training induced brain plasticity in stroke studied therapy for aphasia following stroke (Cochrane Review). To calculate these statistics, ultrasound results Positive predictive value %must be compared to the established gold standards, true positives usually angiography, surgery or autopsy findings. The A 100 true positives false positives simplest statistic compares the outcome of each test as either positive or negative. A true-positive result indi Negative predictive value %cates that both tests are positive. A false A 100 true negatives false negatives positive result means that the gold standard is nega tive, indicating the absence of disease, while the non invasive study is positive, indicating the presence of disease. A false-negative result occurs when the non Extracranial ultrasound invasive test indicates the absence of disease but the gold standard is positive. True-positive and true in acute stroke negative results can be used to calculate sensitivity the most important diagnostic question in ultrasono and specificity. Sensitivity is the ability of a test to graphy is which extra and intracranial vessel(s) is/are correctly diagnose disease. It can be calculated by stenotic or occluded and can it/they be responsible for dividing the number of true-positive tests by the total the clinical symptoms. Note that clinically silent sten number of positive results obtained by the gold otic processes might also influence the cerebral standard. Specificity is the ability to diagnose the absence Because of the interactions between extra and intra of disease and is calculated by dividing the true cranial hemodynamics, both extracranial and intracra negative by the total number of negative results nial ultrasound techniques should be performed in obtained by the gold standard. Overall accuracy can be Doppler ultrasonography is the primary non calculated by dividing the number of true negatives invasive test for evaluating carotid stenosis. Images are produced can be highly variable, based on the incidence of with the brightness-mode (B-mode) technique and disease in the patient population. Because the sometimes color flow information is superimposed on 58 patient population referred to the ultrasound lab is the grayscale image. By convention, the color of the Chapter 4: Ultrasound in acute ischemic stroke pulsating artery is red. The sonographic characteristics of symptom spectral analysis and find the highest velocity or fre atic and asymptomatic carotid plaques are different. After assessment of the anterior circulation, Symptomatic plaques are more likely to be hypoechoic the sonographer should assess the vertebral circulation. Evaluation of arteries can be identified with a probe parallel to the thesurfaceoftheplaquehasnotbeendemonstratedto carotid: angle the probe laterally and inferiorly. The vertebral artery runs perpendicular to basis of the waveform and spectral analysis of the vertebral processes. Use of color flow Doppler enables the more rapid Spectral (velocity) analysis is essential to identify sten identification of vessels (especially the vertebral osis or occlusion. An important general rule for ultra artery) and often helps identify the area of highest sound is the greater the degree of stenosis, the higher velocity, reduces scan time and may help in diagnosis the velocity. Doppler ultrasonography is the primary noninva Blood flow can be laminar, disturbed or turbulent. Symptomatic and asymptomatic carotid plaques When no stenosis is present, blood flow is laminar. When a small degree of stenosis is present, the blood flow becomes disturbed and loses its laminar quality. Even in normal conditions, such flow can be seen Degree of stenosis around the carotid bulb. Some sonographers characterize the degree of sten In normal hemodynamics, as vessel length osis based on diameter or area reduction but estima increases so does resistance. With increasing radius, tion of stenosis solely based on this criterion is not the resistance decreases significantly. More than 300 cm/s systolic velocity could be measured in the stenotic area depicted by the color mode. When possible, laboratories should perform their own correlations with angiographic measurements Doppler ultrasonography associated with stenosis for quality control. Near occlusion: a markedly narrowed lumen on Imaging can be used to downgrade stenosis in the c-Doppler ultrasound. Total occlusion: no detectable patent lumen is seen on grayscale ultrasound, and no flow is seen A severe carotid stenosis is shown in Figure 4. Most studies consider carotid stenosis of 60% or 60 With stenosis over 90% (near occlusion), veloci greater to be clinically important. This equals a ties may actually drop as mechanisms that maintain peak systolic velocity over 125 cm/s. With stenosis Chapter 4: Ultrasound in acute ischemic stroke over 90% (near occlusion), velocities may actually of the ultrasound system. In high-grade subclavian stenosis an alternating flow, or even a retrograde flow, can be detected within With ultrasound, the intimal-medial thickness of the carotid artery can be measured. Diagnosis is frequently reached through Section 1: Etiology, pathophysiology and imaging Table 4. Highlights of the guidelines of the European Federation of Neurological Societies [5]. Identification rates decline with and parenchymal structures can be correctly advancing age. The mean velocity analysis is not enough to the accuracy of ultrasound for detecting identify intracranial vessel abnormalities. Flow velocities are determined by spectral In an acute stroke study the ability of duplex Doppler sonography using the color Doppler ultrasound to diagnose main stem arterial image as a guide to the correct positioning of the occlusions within the anterior circulation was Doppler sample volume. More data are needed to assess the frequency of monitoring for clot dissolution and enhanced recanalization and to influence therapy (Type U). Type A: established as useful/predictive or not useful/predictive for the given condition in the specified population. Type B: probably useful/predictive or not useful/predictive for the given condition in the specified population. Type C: possibly useful/predictive or not useful/predictive for the given condition in the specified population. Type U: data inadequate or conflicting; given current knowledge, test/predictor unproven. Class I: evidence provided by prospective study in broad spectrum of persons with suspected condition, using a gold standard to define cases, where test is applied in blinded evaluation, and enabling assessment of appropriate tests of diagnostic accuracy. If a pathological finding is present, the proximal Stenosis and occlusion in posterior and distal vessel segments should also be evaluated. Alter reduced flow signals in vessel segments proximal ation of flow velocities and turbulence, at least 30 to the occlusion. For example, if patients present Basilar artery stenosis and occlusion with middle cerebral artery symptoms, the insonation Transforaminal and transtemporal insonation allows begins with the non-affected side. The waveforms and alization of the distal part of the basilar artery appears systolic flow acceleration are compared to the non to be difficult even using echo-enhancing agents. Fast-track neurovascular ultrasound examination Recently, a practical algorithm has been published for urgent bedside neurovascular ultrasound exam Recently, a practical algorithm has been published ination with carotid/vertebral duplex and transcra for urgent bedside neurovascular ultrasound examin nial Doppler in patients with acute stroke. Extracranial carotid/vertebral duplex may reveal an additional lesion often responsible for intracranial flow disturbance. Start on the affected side in transverse B-mode planes followed by color or power-mode sweep from proximal to distal carotid segments. If time permits or in patients with pure motor or sensory deficits, examine cervical portion of the vertebral arteries (longitudinal B-mode, color or power mode, spectral Doppler) on the affected side.