Richard Morgan Bain, MD

• Professor of Medicine

https://medicine.duke.edu/faculty/richard-morgan-bain-md

Stenoses are the most common lesion antibiotics zinc deficiency purchase clindamycin with american express, found in 90% of patients with Takayasu arteritis antibiotic names medicine order clindamycin no prescription. Patients often have poststenotic dilatations and other aneurysmal areas medication for uti pain over the counter purchase genuine clindamycin line, reported up to 45% virus lesson plans clindamycin 300 mg with amex. Endothelial activation leads to a hypercoagulable state predisposing the patient to thrombosis antibiotic injection for strep purchase 150 mg clindamycin visa. Congestive heart failure in individuals with Takayasu arteritis may occur as a result of hypertension antibiotics you can give dogs discount clindamycin 150 mg with mastercard, aortic root dilation or myocarditis. Evidence for an autoimmune etiology is supported by circulating antiaortic antibodies and antiendothelial cell antibodies found in the sera of patients with Takayasu arteritis. Immunoglobulin G (IgG), IgM and properdin deposits are found in lesions from pathologic specimens. The biomarker pentraxin 3, a protein closely related to C-reactive protein, may be positive in some patients with active disease with a normal C-reactive protein. Determining Disease Activity It is a major challenge because of poor correlation among clinical, laboratory, radiologic and histologic data. However, the clinical usefulness of this test remains uncertain and its correlation with disease activity has been questioned. Imaging Studies During the chronic pulseless phase, chest radiography may show cardiomegaly, decreased pulmonary vascular markings, irregular contour of the descending aorta, dilation of the aortic arch and linear calcification of the aortic wall. Duplex color flow Doppler ultrasonography may reveal mural thickening and turbulent flow in the carotid arteries and abdominal aorta, stenosis and poststenotic dilation in the abdominal aorta, stenosis or occlusion of subclavian arteries and distal dampened monophasic flow in the brachial arteries. Echocardiography can detect aortic root dilation, coronary artery involvement and the aortic and mitral valve regurgitation associated with Takayasu arteritis. Conventional thoracic and abdominal aortography provides the most complete and accurate assessment of the aorta and its major branches. In children, the most commonly involved arteries in descending order are the abdominal aorta and renal arteries, thoracic aorta, subclavian artery, carotid artery and pulmonary artery. Less commonly involved are the superior mesenteric, celiac, vertebral, hepatic and coronary arteries. Surgical Management Whenever feasible, anatomic correction of clinically significant lesions should be considered, especially in the setting of renal artery stenosis and hypertension. Severe or progressive changes may require aortic surgery with or without valve replacement. Because of the high prevalence of subclavian and carotid stenoses in Takayasu arteritis, severe symptomatic stenoses of these vessels should be treated by grafts that originate from the aortic root and not from an arch vessel to another arch vessel. The latter may be followed by loss of the graft because of new stenosis in an initially spared subclavian or carotid artery. Conversely, a graft from the ascending aorta is a safer long-term conduit because the ascending aorta in Takayasu arteritis essentially never becomes stenotic. Mesenteric and celiac artery stenoses are usually asymptomatic and only rarely require surgery. Angioplasty and intravascular stents have met with restenosis far more often than bypass, which is preferred whenever feasible. It is always best to operate on patients who are in remission; however, judgment of disease activity in Takayasu arteritis may be difficult. Consequently, all bypass surgeries should include vascular biopsy specimens for histopathologic evaluation. Findings from surgical specimens may help guide the need for postoperative immunosuppressive treatment. However, although 60% of patients respond to this treatment, 40% relapse on steroid taper. Patients not responding to corticosteroids or who relapse during corticosteroid taper require an additional agent. Symptoms of patients who relapse on corticosteroid taper may be controlled with weekly infusions of methylprednisolone (30 mg/kg, not to exceed 1 g/week). However, extensive use of these infusions is associated with significant steroid-induced toxicity if continued for any significant period. Methotrexate, infliximab, etanercept, cyclosporine, cyclophosphamide and mycophenolate mofetil also allow disease control and weaning from steroids. The presence of antiendothelial antibodies and plasmablast expansion in patients with active Takayasu arteritis suggest a role for B-cell based therapies. Anecdotal reports of matrix metalloproteinase inhibition using minocycline suggest that this may be a useful adjunctive therapy which may also allow lower doses of corticosteroids, and thus reduced toxicity. Chronic inflammation leads to stenosis of the involved vessels and rarely aneurysms. Morbidities are related to ischemia and hypertension and include congestive heart failure, transient ischemic attacks, stroke and visual disturbances. Chronic, low-grade dissection of the aorta may cause recurrent chest pain for years. Upon autopsy, children with Takayasu arteritis who have died from acute rupture of the aorta have often been found to have evidence of multiple small dissections that did not progress. Is (18)F-fluorodeoxyglucose positron emission tomography scanning a reliable way to assess disease activity in Takayasu arteritis. Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Takayasu arteritis is a chronic inflammatory disease of the aorta and its major branches. The disorder is a large vessel vasculitis (often granulomatous) of unknown origin that has been reported in pediatric patients as young as age 6 months and in adults of every age. Despite the term pulseless disease, which is a synonym for Takayasu arteritis, the predominant finding in individuals with Takayasu arteritis is asymmetrical pulse. Anti-tumour necrosis factor therapy in patients with refractory Takayasu arteritis: long-term follow-up. Takayasu arteritis: utility and limitations of magnetic resonance imaging in diagnosis and treatment. Unfortunately, such clear cut clinical practice guidelines are not available for pediatrics population. Heart failure in infants and children is becoming an increasingly important cause of hospital admissions globally. The last two decades have witnessed huge advances in the field of pediatric cardiology and cardiac surgery with recourse to aggressive cardiac catheter interventions and complex cardiac surgery in infants and small children. Congestive heart failure can be divided into a low cardiac output and a normal cardiac output state. Low output state is defined as the inability to supply sufficient cardiac output to keep up with metabolic demands of the body. Normal output state is defined as an ability to supply sufficient cardiac output but with elevated ventricular filling pressures. A child is said to be in cardiogenic shock if tissue perfusion is compromised secondary to pump failure or due to the low cardiac output state. None of these are perfect scoring systems and have not been validated adequately in large numbers of children with congenital heart disease. Extrinsic factors act by impeding venous return to the heart leading to a low cradic output state. Extrinsic causes include acute and chronic constrictive pericarditis pericardial effusions and sometimes large pleural collections or large pneumothoracis. Similarly congenital or acquired defects causing right or left ventricular pressure overload lead to ventricular hypertrophy which is associated with diastolic dysfunction. Diastolic dysfunction often referred to as restrictive physiology is a situation where there is increased resistance to left or right ventricular filling due to stiff or noncompliant ventricles giving rise to symptoms of congestion. It is important to recognize scenarios of predominant diastolic dysfunction since inotropes may worsen diastolic dysfunction. The normal neonate has a restrictive physiology and exemplifies left ventricular diastolic dysfunction. Effect of Heart Failure Heart failure if untreated goes on to develop diminishing cardiac output resulting finally in end-organ dysfunction, failure and death (Flow chart 1). These may be considered as a hemodynamic defense response aimed at improving myocardial systolic, diastolic function, overall myocardial performance and thereby increasing cardiac output. Congenital or acquired defects causing right or left ventricular volume loading sustain normal cardiac output to meet the needs of the body (Flow chart 2). Left to right shunting or a protected pulmonary circulation in cyanotic heart disease. Older children and young adults present typically with palpitations due to the compensatory tachycardia, and with worsening exercise tolerance progressing finally to breathlessness at rest and in the supine position. This myocardial remodeling leads ultimately to myocardial dysfunction and worsening or refractory heart failure with a tendency to malignant arrhythmias and finally death (Flow chart 2). There may be fissural fluid, small basal pleural effusions and occasionally florid pulmonary edema. Conditions with large left to right shunts or pulmonary overcirculation have increased pulmonary vascular markings or plethora. Sometimes the contour of the heart may provide a clue to the underlying structural heart defect. Echocardiography (Echo) also provides useful information about ventricular volumes and ventricular systolic and diastolic function. A thorough study very effectively confirms or excludes structural Minimize the Mismatch between Metabolic Demand and Supply All attempts must be made to minimize the mismatch between metabolic supply and demand. Factors that increase metabolic demands such as fever, anemia, intercurrent infections, chest infections, endocarditis, hyperthyroidism, rheumatic activity, tachyarrhythmias must be assiduously looked for and aggressively treated. Oxygen therapy and good airway management are useful in reducing the work of breathing and improving tissue oxygen delivery. The rationale for use has been the increased sodium and water loss induced by diuretics. Diuretics from different groups (a­c) can be combined for greater efficacy: (a) Loop diuretics. Furosemide It continues to be the principle drug used in volumeoverload conditions to decrease pulmonary congestion and thus decrease the work of breathing. The rationale for the use of furosemide is the increased water and salt loss through the kidney. Long-term use has been associated with sensorineural hearing loss in a small number of patients. However, currently it is the least toxic diuretic and one for which maximum experience is available. Torasemide is a loop diuretic more potent than furosemide, (10 mg of torasemide is equivalent to 40 mg of furosemide), has a higher bioavailability and a longer duration of action. A phenomenon associated with diuretic use is braking or refractory edema induced by increasing resistance to diuretic use with reducing urine output. Adult data has shown that combination therapy with thiazides or with metolazone increased sodium and water excretion with improved diuretic efficacy. A small pediatric study has also confirmed treatment benefit with combination of furosemide and metolazone. This is achieved by a number of drugs that improve cardiac output and relieve symptoms. Aldosterone antagonists (Spironolactone) the rationale for use are its multiple effects apart from reduced sodium and water retention. These drugs have the additional benefic effect of: (1) an improvement in tachycardia-improving oxygen demand-supply balance, (2) reduced myocardial apoptosis and fibrosis, and (3) antiarrhythmic effect. Hydralazine It is a peripheral vasodilator that is safe in patients with renal impairment as it does not produce much hyperkalemia. Systemic Disorders Beta-blockers (Carvedilol, Metoprolol) Beta-blockers act by the following mechanisms-they cause slowing of heart rate-improving oxygen demand supply balance, reduce myocardial apoptosis and myocardial fibrosis. Pediatric literature includes only retrospective small studies involving carvedilol, metoprolol. Majority of the studies show improvement in symptoms, systolic function, and synergism with other therapy. Current practice in many units including ours is to use carvedilol as adjunctive therapy for systolic ventricular dysfunction (cardiomyopathy, myocarditis and congenital heart disease). Table 6 provides dosages of the drugs (other than digitalis) used to treat heart failure in children. Angiotensin-converting Enzyme Inhibitors (Captopril, Enalapril, Ramipril) these drugs improve cardiac output by afterload reduction. Thus, benefic effects include reduced sodium and water retention, reduced myocardial fibrosis and reduced inhibition of nitric oxide release along with reduced breakdown of vasodilatory bradykinin. Thus, the net effects are the reduction in systemic afterload along with symptomatic improvement. The adverse effects noted were hypotension, renal injury and occasionally death in very bad hemodynamic substrates. Another important side effect is a troublesome cough which is caused due to decreased breakdown of vasodilatory bradykinin. The maximum pediatric data is on captopril and enalopril though enalopril has the advantage of less dosing requirements-once to twice/day. The investigative tools essentially remain the same as highlighted in the text earlier, that is to assess the degree and cause of decompensation and to investigate for any precipitating cause- anemia, infections, endocarditis, etc. Gentle volume augmentation and judicious use of inotropic agents remains the initial approach for any child presenting with acute decompensation. Before the use of inotropic agents occult hypovolemia needs to be recognized and treated.

Increase in osteoclastic activity and suppression of osteoblastic function can cause osteopenia or osteoporosis antimicrobial resistance ppt 300 mg clindamycin mastercard. The recipient may need exogenous dose during stressful situations even several weeks after the withdrawal of the drug infection 4 weeks after wisdom teeth extraction 150 mg clindamycin with mastercard. Normal response would be serum cortisol concentration greater than 20 µg/dL after cosyntropin antimicrobial wall panels cheap 300 mg clindamycin overnight delivery. Any measurement of serum cortisol must be done after stopping prednisolone for 48 hours (or substituting with an equivalent dose of dexamethasone) antimicrobial ointments purchase clindamycin american express, as prednisolone cross-reacts significantly in the cortisol assay antibiotic resistant pneumonia clindamycin 300 mg free shipping. The adverse effects of glucocorticoids depend on the dose and potency of the preparation and the duration for which it is administered antibiotics benefits order clindamycin online. Oral prednisolone in a dose more than 5 mg/m2 body surface area per day is liable to cause adverse effects when used for longer than 21 days at a stretch. The timing and rate of withdrawal of steroids is determined by the response of the primary disease for which it is used. Sometimes, the development of severe systemic toxicity or intercurrent infection in the recipient may necessitate earlier withdrawal of the drug. When the drug is withdrawn due to toxicity or in a case of drug misuse or abuse, the dose is halved every 7­14 days till the physiological replacement dose of 10 mg/m2 daily of hydrocortisone or almost 2. At this point, the total daily dose is given once a day early morning on waking for 14 days and thereafter reduced by 0. If the patient is clinically stable, has normal appetite and vitals, the drug can be stopped. A practical guide to the monitoring and management of complications of systemic steroid therapy. Germ cells migrate in this area under the influence of signaling molecules and proliferation of coelomic epithelium gives rise to sex cords. It has long been thought that the development of testis from undifferentiated gonad is an active process driven by key genes and absence of these leads to ovarian differentiation in a passive manner. However, emerging evidence indicates that ovarian development is also an active process. Problems related to genital development, unlike many other malformations, often lead to stigmatization of the child and family and hence need to be handled with great care and sensitivity. A plethora of genes, signaling mechanisms and transcription factors are involved in each step of sex development and differentiation; however, a detailed discussion of genetic and molecular mechanisms is beyond the scope of this chapter. A consensus statement published in 2006 introduced several new terminologies Table 1) to replace older diagnostic labels. In the latter case, external genitalia are normal since Leydig cell function is not affected. It causes enlargement of the phallus, fusion of labioscrotal folds to form scrotum and fusion of the urethral folds from posterior to anterior direction to form a penile urethra. Actions of these hormones and derivatives of primitive genital structures in male and female are summarized in Flow chart 1 and Table 3 respectively. Steroidogenic Pathways Steroid biosynthesis takes place from cholesterol in the steroidogenic organs (principally adrenals, gonads and placenta). A block in any step leads to increased precursor which may be diverted to unaffected pathways. The elevated Flow chart 1 Development of the reproductive system the diagnosis can be made by newborn screening done on a filter paper sample taken after 72 hours of life or on a peripheral venous sample. The management of 21-hydroxylase deficiency is discussed briefly in Box 2 and in detail in Chapter 44. In addition, maternal virilizing tumors or androgen intake can also be underlying causes. Boys do not have ambiguity (since excess androgen will not affect male external genitalia in utero), hence are at risk of missed diagnosis, adrenal crisis and death. The severity of the mutation influences the expression of enzyme activity with the classic form (either salt wasting or simple virilizing) resulting from less than 5% of the enzyme activity. The simple virilizing form (20­25%) presents with androgen excess without clinical features of salt wasting. The nonclassic form presents with premature adrenarche or symptoms of hyperandrogenism at puberty but not with genital ambiguity. Since there is no ambiguity, many cases may present with delayed puberty or primary amenorrhea or infertility (as there is no functioning ovarian tissue). The extent of functioning testicular tissue determines development or absence of Mьllerian or Wolffian structures. Although several genes have been identified to be associated with gonadal dysgenesis Table 5), a molecular cause can be identified only in 20% of the cases. Disorders of Androgen Biosynthesis Box 1 lists the disorders of androgen biosynthesis. Variable features may be seen depending on severity of defect ranging from hypospadias, micropenis, cryptorchidism. Some of the important clinical and biochemical features of these disorders are summarized in Table 6. External genital phenotype varies from near normal female genitalia to a variable degree of ambiguity to near normal penis. The gonads may be a combination of fibrous streaks or dysgenetic testes with or without one normal testis located anywhere along the path of testicular descent. Histology may be different between two gonads as well as within a single gonad giving rise to the term mixed gonadal dysgenesis. Depending on testicular differentiation, Mьllerian structures may or may not be present. Malignancy risk is high (30­40%) with intra-abdominal gonad, thereby needing gonadectomy in female sex of rearing and in male sex with inability to surgically bring the gonads into the scrotum. Testes may be undescended and the vas may be embedded in close proximity to the uterus. Gonads may be ovotestis on one side and testis or ovary on the other (50%), ovotestes on both sides (30%) or testis on one side and ovary on other (20%). The ovary is usually in its normal location but testes or ovotestes are most commonly seen in the inguinal region, although can be intra-abdominal or rarely scrotal. External genitalia are ambiguous in most of the cases and variable degree of androgen effect may be seen. Individuals with a uterus and lack of significant virilization have potential for menstruation and pregnancy if reared as females. Delay in recognition may also lead to wrong sex assignment causing distress to parents and significant social complications. In developing countries delayed presentations are very common, therefore leading to highly variable clinical presentation Table 7). Assessment for other organ anomalies and developmental delay to rule out syndromic associations Table 8). Clinical Evaluation History Privacy and confidentiality of patients and family should be strictly observed during the entire process of evaluation. Specific points to be noted in the history include: · Detailed history of pregnancy including signs of virilization in mother (virilizing tumors, placental aromatase deficiency), medication use (androgenic progestins, danazol, antiandrogens). Gonads should be palpated between thumb and other fingers in inguinal or labioscrotal area and are more easily found in standing or squatting position. Stretched phallic length should be taken from pubic ramus to tip of phallus excluding foreskin. In the newborn, a length of less than 2 cm is consistent with micropenis and clitoral length of greater than 1 cm with clitoromegaly. Isolated unilateral inguinal testes or isolated glandular or coronal hypospadias do not merit extensive investigations. Hypospadias, if present, should be further described as per the location of the urethral meatus (glanular, also called glandular, subcoronal and penile are the most distal, moving with severity of hypospadias to penoscrotal and perineal). Labioscrotal folds are assessed for the degree of fusion which is classified as no fusion, posterior fusion, partially fused hemiscrotum and fully fused scrotum. Levels even at birth are well above the female levels in the presence of functional testes. An ultrasound of the pelvis can detect the presence of inguinal gonads and visualize the uterus. Further testing depends on outcome of these initial tests and as per clinical features as mentioned in algorithms 1 and 2 (Flow charts 3 and 4). Analogies of common congenital malformations and pictorial explanations of genital development can be used to explain the condition. In addition, in cases presenting late, gender identity, gender role and preferences of the patient also need to be considered. Those presenting in late childhood or adolescence with male like external genitalia and male gender identity may be occasional exceptions. A positive response indicates androgen responsiveness and improves cosmetic appearance and urinary stream in boys. Appropriate sex steroid replacement needs to be started at the pubertal age in conditions where spontaneous development does not occur. Reduction clitoroplasty when performed should preserve the neurovascular bundle to maintain sexual sensitivity. In children with androgen biosynthetic defects raised as females, gonadectomy is performed prior to puberty to avoid risk of virilization. In male sex of rearing, surgical procedures include orchiopexy, chordee corrections, hypospadias repair and sometimes mьllerectomy. Inguinal and scrotal testis in dysgenesis needs to be periodically evaluated for malignancy by palpation and ultrasound. Carcinoma in situ and gonadoblastoma may occur and also invasive tumors like dysgerminoma and seminoma are likely. A stepwise approach including history, examination and judicious use of investigations is necessary. Increasing international cooperation in the field of endocrinology has improved availability of tests like urine steroid profile and genetic studies. Communication with the family is of prime importance and should be done by an experienced team with appropriate protocols. Etiology, clinical profile, gender identity and long-term follow-up of patients with ambiguous genitalia in India. Risk of Malignancy Malignancy risk is high (20­50%) in intra-abdominal gonad with Y chromosome material in cases of gonadal dysgenesis, Frasier Chapter 44. Many aspects of this condition are still not clearly elucidated despite intensive research for over 100 years. Since transinguinal descent begins only by the 7th month of gestation, preterms have an incidence of 30% at birth. The incidence is increasing probably due to increased exposure to environmental chemicals and estrogen. Intra-abdominalpressureplays an important role as conditions such as prune-belly syndrome, cloacal exstrophy, omphalocele are associated with an increased incidence. The gubernaculum plays a significant role; both mechanical and hormonal factors are involved. It is not firmly attached to the scrotum in cases of cryptorchidism and hence testes are not pulled into the scrotum. Dysmorphic syndromes: Down, Klinefelter, Noonan and Prader-Willi syndromes are associated with cryptorchidism. Infertility results if there is a delay in treatment-33% in unilateral cases, 66% in bilateral cryptorchidism. There is a 40% increased risk of testicular cancer; seminoma is the most common tumor in untreated testes. The testes remain tethered to the future inguinal region as the fetal abdomen grows. Differential growth of vertebrae and pelvis until 23 weeks of gestation contributes to transabdominal descent. Androgen (testosterone and dihydrotestosterone) production and action are required for this migration and hence a normal hypothalamic-pituitarygonadal axis is a prerequisite. Patients with 5-reductase deficiency and partial androgen insensitivity can complete the intra-abdominal phase but fail to undergo inguinoscrotal descent. A history of previously palpable testes and history of inguinal surgery in older children are important. Other malformations such as imperforate anus, esophageal atresia, neural tube defects and ventricular septal defects are seen with higher frequency (46%) in bilateral cryptorchidism as compared to unilateral undescended testes (10%). Retractile testes are found in 20% normal boys between the ages 1 year and 5 years and are due to a hyperactive cremasteric reflex. Ectopic testes (5­10%) exit the external inguinal ring but get misdirected into the superficial inguinal pouch, femoral or perineal region. Vanishing testes (3%) occur due to in utero torsion of testicular vessels after 14th week of gestation. Extensive research has implicated some factors but exact mechanism remains elusive. If there is associated severe degree hypospadias, the term microphallus is used as it could represent a small penis or an enlarged clitoris. Very little penile growth occurs after the first year of life till puberty when it resumes because of increased testosterone production. However, the most common consultation to a pediatrician for micropenis will be in the context of an obese boy brought for evaluation of apparently small genitalia. No endocrine evaluation is required as the penis is generally of normal length and the apparent smallness is due to the penis being concealed in the suprapubic pad of fat. Medical Therapy the age of treatment of cryptorchidism has been pushed up over recent years to 6 months as the chances of spontaneous descent are rare after 6 months and there is a higher possibility that fertility may improve with early intervention. Patient selection is crucial as distally located testes are more likely to descend than intraabdominal testes. Testicular degeneration after 14 weeks of gestation causes isolated micropenis with bilateral undescended testes. Defects in testosterone steroidogenesis and testosterone action can present with micropenis, but they are usually in the context of other major external genitalia abnormalities like a severe degree of hypospadias with or without bilateral cryptorchidism (see also Chapter 44.

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Corneal diseases are a major cause of blindness worldwide antimicrobial lotion buy clindamycin 150 mg with visa, second only to cataract in overall importance antibiotic powder clindamycin 150 mg low cost. Almost 20% of childhood blindness is estimated to be caused by corneal blindness virus mutation rate buy cheap clindamycin 150mg online, with high regional variances from 2% to 50% antibiotic resistance plasmids in bacteria order clindamycin 150 mg line. Corneal and ocular surface disorders in children can broadly be classified as developmental or acquired (infections antibiotic for pneumonia 300 mg clindamycin visa, trauma virus 46 states cheap clindamycin 150mg on line, tumors, nutritional diseases, immune mediated, others). Megalocornea It is a rare congenital condition characterized by unilateral/ bilateral, symmetric corneal enlargement. If the horizontal corneal diameter is more than 12 mm in the neonate or more than 13 mm in adult, megalocornea is present. Three patterns of megalocornea are: (1) Simple megalocornea; (2) Anterior megalophthalmos or X-linked megalocornea-associated with iris and angle anomalies, lens subluxation and cataract; and (3) Buphthalmos resulting from congenital glaucoma. Keratoglobus It is a bilateral generalized, noninflammatory thinning and anterior protrusion of the entire cornea from limbus to limbus. The associated corneal edema gradually subsides leaving an essentially clear cornea with vertical striae. Corneal edema in infantile glaucoma is due to epithelial and stromal edema and is associated with an enlarged globe and photophobia. U in cornea are usually of infectious etiology and are dealt in detail later in the chapter. Sphingolipidoses-Fabry disease, caused by the absence of alpha galactosidase A, presents with whorl like opacity on the cornea. Posterior keratoconus: A posterior corneal depression with minimum overlying opacity. A corneal opacity with adherent iris strands and corneolenticular contact or cataract. Ultrasound biomicroscopy is extremely useful imaging modality to assess details of the anterior chamber in the presence of hazy cornea. Mesenchymal dysgenesis of the anterior segment includes congenital anomalies of the iris and iridocorneal angle along with posterior corneal defects. This occurs as an isolated anomaly or associated with other anterior segment anomalies. In the latter situation it occurs with nanophthalmos or as a part of microphthalmos. Complicated forceps deliveries can result in periorbital ecchymosis and corneal edema. In the latter type child has tearing and light sensitivity without nystagmus; (2) Congenital hereditary stromal dystrophy; and (3) Posterior polymorphous dystrophy. In cases where fungal infection is suspected topical 5% natamycin is started to cover the common filamentous fungi. Other antifungals that can be used include amphotericin B, voriconazole and itraconazole. Scleral involvement or endophthalmitis are the indications for systemic antibiotics. Ocular Involvement in Exanthematous Fever Keratoconjunctivitis may occur in patients suffering from viral infections such as herpes and measles. Corneal thinning with ulceration may occur in generalized malnutrition and vitamin A deficiency in particular. These ulcers may get secondarily infected and may perforate resulting in the formation of staphyloma. Bacterial and viral infections are major causes of septic neonatal conjunctivitis, with Chlamydia being the most common infectious agent. Infants may acquire these infective agents as they pass through the birth canal during the birth process. Among children, amblyopia is the major concern, as altered corneal transparency due to keratitis prevents normal neurophysiological development. Incidence of blindness caused by keratitis in children is 20 times higher in tropical developing countries when compared to developed countries. Factors influencing this disparity are prevalence of low socioeconomic status, incomplete immunization profile and systemic diseases, including hypoxic encephalopathy, pulmonary stenosis, protein-energy malnutrition, multiple congenital anomalies and prematurity. Ocular trauma is the most important predisposing factor for infectious keratitis in children. Other factors are chronic steroid use, secondary infections postexanthematous fever, ocular rosacea, previous ocular surgeries, congenital facial paralysis, previous herpetic infection, dry eye and eyelid abnormalities. Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa are among the common causative organisms. Bacterial keratitis is characterized by intense suppuration, congestion, tearing and photophobia. The rapidly spreading infections lead to necrosis, ulceration, abscess formation and finally corneal perforation. In tropical climates filamentous fungi such as Fusarium and are the most common causative organisms. Signs in this type of keratitis are more severe than symptoms in the initial stages. Epithelium breakdown results in stromal ulceration and hypopyon, which may further lead to formation of descemetocele and corneal perforation. Characteristic satellite lesions may be seen peripheral to the focal area of infiltration. The term Xerophthalmia (from the Greek word xeros, meaning dry), covers all ocular manifestations resulting from vitamin A deficiency. The serious eye manifestations of vitamin A deficiency leading to corneal destruction and blindness, i. Clinical manifestations, management and prophylaxis are described in detail in Chapter on Vitamin A Deficiency in Section 22 on Nutritional Disorders. Management Treatment-based on culture and sensitivity testing is difficult as the rate of culture positivity is low. Empirical treatment consists of topical fluoroquinolones, fortified cefazolin 5% (to cover grampositive organisms) and fortified tobramycin 1. Common causes of blunt trauma are Gilli danda (a sport involving wooden stick hitting a small polished wooden cylinder, popular in India), fire cracker injury and cricket ball injury. These present with a wide variety of injuries from periocular soft tissue hematomas, lid lacerations, corneal abrasions, traumatic iritis to orbital wall fractures. Projectile trauma represents the effect of a moving object transferring its kinetic energy to the periocular tissue. This ranges from a corneal abrasion to hyphema, orbital fracture to a ruptured globe. Shaken (Battered) Baby Syndrome this is widely recognized as one of the most important forms of child abuse. Clinical findings in affected infants include subdural/subarachnoid hemorrhage, intraretinal/vitreous hemorrhages, hypoxic-ischemic brain injury and fractures at various stages of healing and cutaneous injuries. Histologically they are lined by conjunctival epithelium and the subepithelial tissue contains adipose tissue admixed with collagenous tissue. Larger or symptomatic dermoids can be approached by lamellar sclerokeratectomy with primary closure or amniotic membrane transplantation with corneal graft if the defect is deep or full thickness. The larger or cosmetically unappealing ones can be managed by excision of the entire orbitoconjunctival lesion through a conjunctival forniceal approach. Corneal keloids are seen as white, protuberant, glistening masses which involve cornea and anterior segment or even replace the entire cornea. Rarely congenital corneal keloids may be seen in association with other anomalies like peripheral iridocorneal adhesions, anterior segment mesenchymal dysgenesis, aniridia and cataract with anophthalmia. They have been described in children with Lowe syndrome, Rubinstein-Taybi syndrome, and fibrodysplasia ossificans progressiva. Management options include simple excision, lamellar keratoplasty and penetrating keratoplasty. Tumors Nonmalignant tumors of the ocular surface include dermoids and dermolipomas. They may present as an isolated finding or commonly as a part of Goldenhar or Franceschetti syndrome (discussed later). Epibulbar dermoid are benign developmental choristomas (normal tissues in abnormal location), derived from displacement of ectoderm to a subcutaneous location. These lesions are located in regions of the bulbar conjunctiva, limbus, cornea, and/or caruncles. Limbal dermoids are most commonly located in inferotemporal quadrant along the limbus. They may be associated with syndromes such as ring dermoid syndrome with conjunctival extension, preauricular tags, palpebral coloboma, Goldenhar syndrome (preauricular fistulae, preauricular appendages, and epibulbar dermoids or lipodermoids), and mandibulofacial dysostosis of Franceschetti syndrome. They are more commonly found in the Epithelial Conjunctival Tumors Several benign and malignant tumors can arise from squamous epithelium of the conjunctiva: Papilloma: this appears as a pink fibrovascular frond of tissue arranged in a sessile or pedunculated configuration. This benign tumor is often associated with human papilloma virus (subtypes 6, 11, 16 and 18). Hereditary benign intraepithelial dyskeratosis: A rare benign autosomal-dominant condition seen amongst Caucasian, African-American and American-Indians (Haliwa Indians). It is characterized by bilateral elevated fleshy plaques on nasal or temporal perilimbal conjunctiva and buccal mucosa. Small lesions are managed using lubricants and corticosteroids with surgery being reserved for larger lesions. In intraepithelial neoplasia, anaplastic cells are confined to epithelium whereas squamous cell carcinoma displays extension of anaplastic cells through basement membrane into the conjunctival stroma. Tumors in limbal area require alcohol epitheliectomy for the corneal component and partial lamellar sclera-conjunctivectomy with wide margins for conjunctival component followed by freeze-thaw cryotherapy to remaining adjacent bulbar conjunctiva. Extensive and recurrent tumors require adjuvant topical mitomycin-C, 5-fluorouracil or interferon. The acute phase occurs 1­3 weeks after exposure to the triggering agent and is characterized by a systemic prodrome followed by mucous membrane and skin lesions. Ocular findings in the acute phase include intense membranous conjunctivitis and may develop a secondary infectious bacterial conjunctivitis. The chronic stage is characterized by dry eye, lid involvement with entropion, ectropion, trichiasis and damage to meibomian glands. Keratinization of the lid margins and palpebral conjunctiva causes corneal damage via blink-related microtrauma to the corneal epithelium. In acute stage, the ocular surface is protected with intensive lubricants, anti-inflammatory agents and topical antibiotics. Early symblepharon formation is prevented by mechanical lysis of the symblepharon. During chronic phase dry eye is managed intensively and eyelid abnormalities treated. The most common underlying cause being Type 1 hypersensitivity reaction since positive family history of allergy is ubiquitous. Patients present with symptoms of profound itching, excessive tearing, mucous production, photophobia, burning or foreign body sensation. Thick tenacious mucus strands are found in the fornix along with inflammation of the bulbar conjunctiva. Corneal involvement varies from superficial punctuate keratopathy to large epithelial defects. Untreated it can result in secondary infection, stromal ulceration and corneal scarring. This is characterized by presence of large conjunctival papillae at corneoscleral limbus, as a consequence of which superficial vascularized pannus may form. Collections of inflammatory cells rich in eosinophils, present at apices of limbal papillae form Horner-Trantas dots. Vernal keratoconjunctivitis is a self-limiting disease associated with sight-threatening complications. Management aims at control of symptoms and to limit development of vision-threatening complications. Long-term steroid therapy is avoided due to concerns regarding elevation of intraocular pressure or cataract formation. Topical cyclosporine 2% and tacrolimus are newer drugs being used in the management of vernal keratoconjunctivitis. The presenting features are diminution of vision for distance along with frequently changing spectacle refraction. Children have irregular astigmatism, photophobia and in late stages inability to see well with spectacles. The disease generally worsens in the initial years with the process stopping by third to fourth decade. Fleischer ring: Partial or complete annular ring, yellowish brown to olive green in color containing hemosiderin pigment deposited at basal epithelium level. Keratoconus in pediatric age group may be seen at the age of 8­10 years and progresses very fast in this part of the Asian subcontinent. Topographical measures are very useful in diagnosing and following the progression in patients with keratoconus. Management of pediatric keratoconus-evolving role of corneal collagen cross-linking: an update. Corneal ulceration in pediatric patients: a brief overview of progress in topical treatment. Acute management of Stevens-Johnson syndrome and toxic epidermal necrolysis to minimize ocular sequelae. Management Corneal topography helps in staging the disease and monitoring its progress. However, the visual morbidity is high due to inability of the child to complain and consequent delayed presentation to the ophthalmologist. Although pediatric uveitis is rare, bilateral involvement and high visual morbidity leads to legal blindness in children. The presentation of uveitis is many times a part of a larger picture of systemic involvement.

Management and outcome the initial step in treatment is surgical antibiotics for uti new zealand 150mg clindamycin overnight delivery, followed by radiation and/or chemotherapy depending on the age of the patient infection taste in mouth purchase 300 mg clindamycin visa. Surgery remains the initial line of treatment with gross total resections associated with a better prognosis antibiotics for sinus infection not helping discount clindamycin 150mg fast delivery. Although histologically they are embryonal tumors like a medulloblastoma virus or bacteria order clindamycin from india, survival outcomes are generally lower virus us generic clindamycin 150 mg free shipping. Growth and endocrine involvement may be seen in patients with extensive hypothalamic involvement antibacterial yoga socks purchase clindamycin 150mg visa. The diencephalic syndrome (emesis, failure to thrive, and unusual euphoria) is a classical presentation for infants with hypothalamic gliomas. The spontaneous density of chiasmatic tumors is close to that of the cerebral tissue, and homogeneous enhancement is seen postcontrast injection. In patients who present with visual loss or in those with progression of visual symptoms and also in patients with a progressive tumor growth or chiasmatic involvement, treatment is indicated. Surgery of optic nerve tumors is rarely undertaken and is usually a globesparing procedure done in cases with significant proptosis and vision impairment. They can be unilateral or bilateral, involve the chiasma or extend throughout the visual pathway. Clinical course and diagnosis the signs and symptoms depend on the location and the age of the patient. Anterior lesions, confined to the optic nerve anterior to the chiasm present with monoocular visual loss and slowly developing proptosis. Children with posterior lesions present with loss of visual acuity as their presenting complaint. Radiotherapy results in visual stabilization in majority of visual pathway gliomas which are not amenable or only partially amenable to surgery. Chemotherapy is used to delay if not to obviate the need of radiotherapy in children with progressive optic pathway gliomas. In patients with mild symptoms, only observation is recommended, as the natural course of the disease is slow with no immediate threat to vision. Treatment with chemotherapy is needed only if there is tumor progression and radiotherapy is generally avoided. Dysembryoblastic Neuroepithelial Tumor They are benign cortical tumors noted in older children or young adults. They are the most common nonglial brain tumors in children and commonly present in children between 5 years and 14 years. No surrounding edema is seen; (B) the lesion appears hypointense on T1-weighted image. Clinical presentation and diagnosis Tumor growth characteristics vary considerably, which influences the clinical presentation. The clinical symptoms can be classified according to the anatomical position of the tumor Table 14). Management and outcome the treatment of craniopharyngiomas involves surgical resection and radiotherapy. Radiation therapy is however indicated in patients undergoing a subtotal resection. Endocrine abnormalities which may get exacerbated postsurgery needs meticulous management. Immunopositivity for transthyretin (prealbumin) is useful in confirming the diagnosis of choroid plexus tumors. Due to macrocephaly secondary to hydrocephalus, infants can present with head titubations, the syndrome. The treatment of choice is total surgical resection which can be difficult in young infants. Radiation therapy and/or chemotherapy may lead to better disease control for choroid plexus carcinomas. Germ Cell Tumors They are predominantly tumors of midline structures of the pineal and suprasellar regions. The analysis of alpha fetoprotein and beta-human chorionic gonadotropin are useful in establishing the diagnosis and monitoring treatment response. Surgical biopsy is usually needed for diagnosis; however nongerminomatous germ cell tumors may be diagnosed on basis of protein marker elevation. The postsurgical management of pure germinomas involves usage of chemotherapy and reduced dosage radiation. The approach to nongerminomatous germ cell tumors demands more aggression with more intense chemotherapy and craniospinal radiation. Central nervous system tumors are the second most common form of pediatric cancer. The profile of pediatric brain tumors in India is similar to that reported globally with astrocytic tumors being the most common histological type. A majority of pediatric brain tumors are infratentorial in location and primary brain and spine tumors outnumber the metastatic tumors in childhood. Gross or near total excision of tumor is the single most important prognostic factor in deciding the outcome. Late effects can become evident over decades as the brain develops and can affect every body system; thus, needing long-term monitoring in survivors of brain tumors. Metastatic Tumors Childhood acute lymphoblastic leukemias and non-Hodgkin lymphoma are seen to spread to the leptomeninges causing communicating hydrocephalus. Neuroblastomas, rhabdomyosarcomas, Ewings sarcoma, osteosarcoma and clear cell sarcoma of the kidney can metastasize to the brain parenchyma. A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas. This link needs to be investigated for plausible vaccine-preventive strategies for retinoblastoma in developing countries. In bilateral cases, it can arise in one eye, several months before being evident in the other. It is one of the most treatable childhood cancers, with survival rates exceeding 99% in the developed countries. However, 80% of the 8,000 children diagnosed annually with retinoblastoma, live in developing countries, among whom nearly 3,000 die of extraocular dissemination. Treatment abandonment due to illiteracy, limited finances, as well as fear of enucleation remain major impediments. Management of retinoblastoma requires a collaboration between several specialties, viz. The tumor originates in the sensory retina and may grow into the vitreous cavity (endophytic) or, outwards into the subretinal space (exophytic) causing retinal detachment. Diffuse infiltrating pattern with no obvious mass, or an extensive necrotic variant presenting with severe inflammatory reaction leading to pthisis bulbi, are well-known. Spontaneous regression due to complete occlusion of the central retinal artery can occur. Microscopic examination reveals unifocal/multifocal tumor with mitotically active hyperchromatic cells, some differentiated to form Flexner-Wintersteiner (and less frequently HomerWright) rosettes, others simply forming pseudorosettes around blood vessels. Sometimes benign photoreceptor differentiation leads to the formation of fleurettes. The Third National Cancer Survey in the United States reported an average incidence of 11 cases per million population in less than 5 years of age, or about 1:18,000 live-births. This is unique among pediatric malignancies, and provides opportunity for studying geographic and ethnic factors in disease pathogenesis. It is often felt that the incidence may be higher in developing countries, including Central and South America, the Middle-East and India. It is estimated that India has the highest number of affected children with retinoblastoma in the world. Data from the National Cancer Registry Project (1999­2000), Delhi, reported an incidence of 28 cases per million population in less than 5 years of age. High incidence is frequently reported from several African nations, where it accounts for 10­15% of cancers in children. It is widely perceived that retinoblastoma is more frequent among the lower socioeconomic stratum of society. This results from either the tumor causing total retinal detachment, or being visible as a retrolental mass through the pupil. Vitreous hemorrhage can result in a dark red reflex (hemocoria), or black reflex (nigrocoria). However, in developing countries, late presentation with buphthalmia and proptosis (often with a fungating mass) is frequent (~30% from India). In a study from Nigeria, proptosis with conjunctival chemosis was the most frequent presentation. Retinoblastoma can present with rubeosis iridis (neovascularization of the iris), heterochromia iridis (secondary to neovascularization), hyphema (blood in the anterior chamber), glaucoma (secondary to neovascularization, or mechanical Age, Gender and Laterality Retinoblastoma can present at birth. The median age at diagnosis is 24 months for unilateral and 9­12 months for bilateral disease. Delayed presentation with advanced disease is a problem in the developing countries. Retinoblastoma diffusely infiltrating into the retina can be clinically masquerade uveitis and endophthalmitis, resulting in delayed diagnosis. Metastatic disease can present with bone pain, scalp masses, preauricular and submandibular lymphadenopathy, seizures and raised intracranial tension. This duration is reported to be delayed to 8 months in India and 9­12 months in Africa. Causes of the delay include lack of awareness about the seriousness of the disease, fear of enucleation, lack of finances for travel and lack of timely referral by the primary physician. A delay exceeding 6 months from the first clinical sign to diagnosis is associated with 70% mortality. The contrasting scenario between the developed and the developing countries is summarized in Table 1. Clinical examination includes recording the visual acuity, slit-lamp (if possible) or indirect ophthalmoscopic examination. The anterior segment is examined to look for hyphema, rubeosis iridis, iris nodules, corneal edema, cataract, retrolental mass and retrolental fibroplasias to exclude pseudoretinoblastoma. The posterior segment is examined to note whether the mass is exophytic, endophytic or mixed, presence of retinal detachment and to exclude retrolental fibroplasia and Coats disease. Examination under Anesthesia A detailed evaluation of the entire retina, up to the ora serrata, in both eyes is needed. RetCam is a wide angle fundus camera, useful in accurately documenting retinoblastoma and monitoring response to therapy. Differential Diagnoses Benign conditions (pseudoretinoblastomas) often simulate retinoblastoma Table 2). The detection of intraocular calcification is a key element to differentiate retinoblastoma from simulating lesions. In children below 3 years of age, an intraocular calcified mass is most likely a retinoblastoma. However, cost and availability of timely appointment is a limitation in developing countries. Staging the first step in staging is to determine whether the disease is intraocular or extraocular. Intraocular retinoblastoma is localized to the eye and may be confined to the retina or may extend to involve other structures, such as the choroid, ciliary body, anterior chamber, or optic nerve head. Extraocular retinoblastoma, as the name suggests is one in which disease has extended beyond the eyeball. It may be confined to the tissues around the eye (orbital retinoblastoma), or it may have spread to the central nervous system, bone marrow, or lymph nodes (metastatic retinoblastoma). Disease Congenital cataract Coats disease Persistent hyperplastic vitreous Retinal detachment Retinopathy of prematurity Toxocariasis Etiology Intrauterine infections, galactosemia, etc. Chemotherapy may be administered in adjuvant (following surgery) or neoadjuvant (before surgery) setting, depending on specific indications. C Management of Intraocular Retinoblastoma Low-risk Intraocular Retinoblastoma (Stage 0 and Selected Stage 1) Group A is treated by focal therapy alone. Groups B, C and D are frequently treated with 2­6 cycles of chemotherapy (consisting of vincristine, etoposide and carboplatin), along with focal therapy. Direct delivery of chemotherapy (melphalan alone, or in combination with carboplatin and topotecan) in the ophthalmic artery, accessed via cannulation of femoral artery, promises to be a paradigm-changer in the treatment of localized retinoblastoma. Vision may be restored by reversal of retinal detachment, while avoiding the complications of radiotherapy and systemic chemotherapy. This may lead to iatrogenic down-staging of the tumor and increases the chances of subsequent extraocular relapse. These patients should receive 6 cycles of chemotherapy, irrespective of high-risk histological features. Enucleation should be performed as soon as feasible, as delay is proven to increase risk of relapse. This includes tumor invasion through the resection-margin of the optic nerve, or trans-scleral invasion. The enucleation should be performed by an experienced ophthalmologist to obtain a long optic nerve stump (at least 10­15 mm). Treatment includes adjuvant chemotherapy (up to 12 cycles) and orbital radiotherapy. Orbital radiotherapy following enucleation, or at the end of chemotherapy, irrespective of the histopathological findings. Radiation to the involved preauricular and/or cervical lymph nodes is often recommended, though without adequate evidence 4. Patients presenting with optic nerve involvement on imaging should be treated as stage 3 disease. Patients with Metastatic Disease (Stage 4) Until recently, metastatic disease was considered incurable.