Paul Bennett Rothman, M.D.

• Chief Executive Officer, Johns Hopkins Medicine
• Professor of Medicine

https://www.hopkinsmedicine.org/profiles/results/directory/profile/7843104/paul-rothman

Invasion occurs following infection by new noncommensal strains or sometimes treatment 2 discount diamox 250mg otc, facilitated by existing viral respiratory tract infection symptoms torn rotator cuff diamox 250 mg otc. Meningococci and gonococci produce an IgA protease that helps in colonization of mucous membranes by cleaving the proline-rich hinge region of secretory IgA treatment 4 pimples order diamox. Serum antibody against meningococcal antigens symptoms nausea generic diamox 250mg on line, if present medicine measurements cheapest generic diamox uk, can block this spread by complement-mediated bacterial lysis symptoms dizziness nausea purchase diamox. Absence of antimeningococcal antibody is associated with development of meningococcemia. Two additional characteristics of meningococci contribute to its pathogenicity: its polysaccharide capsule and an iron scavenging system which uses host transferrin and lactoferrin. Blockage of small vessels by leukocyterich fibrin clots result in focal hemorrhage and necrosis in major organs particularly skin, heart, central nervous system, adrenals. Diffuse adrenal hemorrhage without vasculitis known as Waterhouse-Friderichsen syndrome may also be seen. Invasive meningococcal disease can have protean manifestations, like bacteremia alone, meningococcemia (sepsis), and meningitis with or without meningococcemia. Occult meningococcal bacteremia usually has nonspecific signs mimicking minor viral infections. This presentation may resolve spontaneously without antibiotics, or can lead to meningitis. Meningitis, the most common invasive meningococcal manifestation, presents with lethargy, headache, photophobia, vomiting, and signs of meningeal irritation. Acute meningococcemia begins with nonspecific viral-like illness with fever, headache, myalgias, vomiting, and diarrhea. The dissemination may also involve joints (suppurative arthritis), pneumonia, and purulent pericarditis/myocarditis. In the recent epidemic reported from Shillong, (N = 110) following signs were recorded among children with invasive meningococcal disease: Fever (100%), headache (56%), vomiting (54%), altered sensorium (26%), purpura/petechiae (24%), seizures (9%) and excessive crying (5%). Meningeal signs were present in 78% and bulging anterior fontanel in 23% below the age of 18 months. For surveillance purpose the case definitions for probable and confirmed meningococcal disease in Indian setup have been proposed. Probable case includes suspected case of acute or bacterial meningitis and positivity for gram-negative Diplococci or ongoing epidemic or with Petechiae/purpura. Complications Complications seen are due to meningococcemia and meningitis per se and immune complex-mediated which become apparent in the second week after the onset of illness. Suppurative complications include raised intracranial pressure (28%), coagulopathy (16%) and hepatopathy (10%) as seen in the recent epidemic from NorthEast. Fever persisting beyond 7 days in a child with meningococcal illness should alert the physician to the possibility of immune complex-mediated complications. Prior antibiotic use, which is common in India, reduces the chances of positive culture. Bacteria may be seen on Gram staining of the buffy coat layer, of a centrifuged blood sample. Studies suggest that effectiveness is 80% to 85% within 3 to 4 years after vaccination. Side effects include pain, swelling, and rare reports of Guillain-Barrй Syndrome especially in adolescents. The vaccine is immunogenic in adults but is unreliable in children younger than 2 years. Mass Reactive Vaccination In India it is carried when disease incidence is 10 cases/100,000 in a given district. Mass immunization with bivalent (A + C) polysaccharide vaccine was carried as a pilot project in India during the Meghalaya outbreaks. Infectious Diseases Care of Contacts Chemoprophylaxis is given to close contacts to eliminate nasopharyngeal carriage, preferably within 24 hours of contact with an index case. Children may be given rifampin (10 mg/kg orally q 12 hours for a total of four doses; maximum dose: 600 mg; 5 mg/kg/dose for infants < 1 month of age)). Mass chemoprophylaxis is not considered to be useful or epidemiologically cost effective. Differential Diagnosis Meningococcal infection can have overlapping features with sepsis, meningitis, Rickettsial infections and bacterial endocarditis. Encephalitis and viral infections with echoviruses (particularly types 6, 9, and 16), coxsackieviruses (primarily types A2, A4, A9, and A16) may have to be ruled out. Autoimmune disorders like Henoch-Schцnlein purpura, hemolytic-uremic syndrome, Kawasaki disease, idiopathic thrombocytopenic purpura, and drug rash can mimic meningococcal disease. It is an infection of the mucus membranes of the genitourinary tract and rarely, rectum, oropharynx and conjunctiva. Universal screening for gonorrhea is not advised since gonococcal infections in females are commonly asymptomatic. Disseminated gonococcal infection may present as tenosynovitisdermatitis syndrome, characterized by fever, rash, and polyarthralgia involving the wrists, hands, and fingers; or as suppurative arthritis syndrome, in which systemic signs are not marked and monoarticular arthritis, often involving the knee, occurs. Due to the legal implications involved, culture is the preferred method of diagnosis. Cephalosporins are the sole class of antibiotics recommended for the treatment of N. Cefotaxime or ceftriaxone are acceptable alternatives in case of nonavailability or drug resistance. Children with fulminant meningococcemia with refractory shock may require hydrocortisone due to adrenal insufficiency. Rare neurologic sequelae like focal deficits, seizures, ataxia and obstructive hydrocephalus may be seen 3­4 weeks after onset of illness. Case fatality in severe disease forms like pyogenic meningitis or septicemia is 5­25% despite advancements in pediatric critical care. Vaccine is recommended only during outbreaks, in high risk children and international travelers. Invasive meningococcal disease presents as meningitis, or meningococcemia (sepsis) or both. It is caused by gram-negative Diplococcus, Neisseria meningitidis, which are normal commensals of the nasopharynxin5­10%ofthepopulation. Young age (children < 2 years), overcrowded living conditions and complement deficiencies (both inherited and acquired) are important risk factors. Children usually present with fever, headache, altered sensorium, purpura/petechiae, meningeal signs and seizures. Important differential diagnosis includes sepsis, Rickettsial infections, bacterial endocarditis, autoimmune vasculitides, coxsackie and echovirus infections. Meningococcal vaccination is recommended in select groups and in outbreak situations. Invasive meningococcal Infection: Analysis of 110 cases from a Tertiary Care Centre in North East India. Indian Academy of Pediatrics recommended immunization schedule for children aged 0 through 18 years, India, 2013 and updates on immunization. An overview of meningococcal disease in India: knowledge gaps and potential solutions Vaccine. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae-2014. Its ubiquitous presence and minimal nutritional needs causes easy colonization and develop reservoirs in sinks or respiratory equipment in hospital setting. Prolonged hospital stay, mechanical ventilation, and central line catheters cause breach in host defense and predisposes to Pseudomonas infection. Pseudomonas aeruginosa has a wide potential to develop resistance to multiple antibiotics by various mechanisms and inappropriate empirical therapy increases the possibility of development of such resistance. Among them the most common infections are as follows: Bloodstream Infection Infectious Diseases Disseminated bacterial infection is seen in burns, neutropenia and malignancies where patient is undergoing chemotherapy. The clinical presentation of septicemia is same as with other gram-negative infection and patient may present in shock. A typical vasculitic skin lesion which differentiates from other gram-negative infection is ecthyma gangrenosum. They are small painful hemorrhagic lesion with necrosis, pink in color to start with and become gangrenous. It is mostly present in moist environment, and easily colonise in sinks, respiratory equipment, mops and disinfectants; even it can survive in distilled water. Being an opportunistic pathogen impaired host defense is the prerequisite to develop infection. These infections further spread from patient to patient on the hands of hospital personnel, by direct patient contact or with the contaminated reservoirs. In developing countries Pseudomonas is a common pathogen in burn wound, febrile neutropenia and patients undergoing chemotherapy and causes most serious infection in ventilator associated pneumonia. It is also the leading cause of chronic lung infection and respiratory failure in cystic fibrosis. In ventilated patient initial slow colonization of Pseudomonas aeruginosa may lead to rapid fulminant infection. Patient presents with fever, chill, cough, cyanosis and tachypnea, X-ray shows bilateral opacities often with cavity formation. Urinary Tract Infection Prolonged use of catheter, instrumentation and urinary tract obstruction predisposes to Pseudomonas infection. Psudomonas Dermatitis Though less severe, community infections occur as folliculitis following bath in swimming pools, paronychia, and toe web infection seen with prolonged exposure to water. The bluish or greenish color pus is suggestive of Pseudomonas infection and is due to the pigment pyocyanin. The surface virulence factor (flagella, pili and lipopolysaccharide) helps in attachment, colonization and invasion. Secreted virulence factor (mucoid, exopolysaccharides, exotoxin A and proteases) damages tissue and produces cytokines causing tissue damage. Impaired host defense mechanism further contributes to the virulence and chronicity of infection. Its single polar flagellum helps in motility and adhesiveness to the cell surface for initiation of infection. The pili present in the outer surface membrane of Pseudomonas, attaches to the epithelial cells at the site of colonization and forms a nidus for local infection. In immunocompromised host it becomes locally invasive and cause systemic infection. Pyocyanin is responsible for greenish sputum in Pseudomonas infection, causes epithelial and endothelial damage to the lung tissue in acute infection. Pyochelin a derivative of pyocyanin is a siderophore helps in deriving iron from the host cell for bacterial growth. Pseudomonas aeruginosa in presence of large bacterial mass communicates with each other through Eye and Ear Pseudomonas is a predominant cause of otitis externa and severe ophthalmic infection (corneal keratitis) following prolonged use of contact lens. Cystic Fibrosis Chronic infection is commonly seen in patients with cystic fibrosis. In cystic fibrosis mucoid strains of Pseudomonas produce large amount of exopolysaccharide (alginate) to form biofilm. The biofilm helps in anchoring the bacteria to respiratory tract, impairs the ciliary movement facilitating colonization. Initial colonizations with nonmucoid strains are slowly replaced with the mucoid strain. These mucoid strains resist phagocytosis and host immune response by the biofilm formation leading to chronicity of the disease with frequent exacerbation. Due to repeated use of antibiotics the organism develops resistance to multiple antibiotics. Due to easy colonization, simple isolation of the organism from the biological tissue is not diagnostic. Isolation of the bacteria from the central body fluid, external devices is diagnostic in the high risk individual. Different mechanisms of resistance are discussed below: Inhaled Antibiotics Inhaled tobramycin, gentamicin, polymyxins and colistin may be used in cystic fibrosis as an adjunct therapy for pneumonia and to prevent bronchiectasis. It does not have the usual trimeric porins characteristic of enteric bacteria, instead it has monomeric porin, which reduces the membrane permeability of the drug leading to very slow entry. Indications of combination therapy are severe sepsis or septic shock; neutropenic patients with bacteremia; burn patients; and endocarditis. However, controversy exists regarding the superiority of combination to monotherapy. In a meta-analysis of randomized control trial including immunocompromised patients with documented sepsis, combination therapy has not shown any reduction in mortality. In Pseudomonas infection efflux mechanism is the major factor contributing resistance to aminoglycosides, fluoroquinolones, and many betalactams. Bacterial Infections Bacterial Destruction Bacterial destruction of beta-lactams by beta-lactamases enzyme is another common method of resistance in Pseudomonas infection. Carbapenamases have wider spectrum of activity and not only hydrolyses carbapenems (meropenem, doripenem and imipenem) but also other beta lactams. They cannot hydrolyze monobactum (aztreonam) and are not inhibited by clavulanate. Pseudomonas aeruginosa is an opportunistic pathogen of the Pseudomonadaceae family and causes infections usually in immunocompromised host. It is one of the most important causes of nosocomial infections including, bacteremia, ventilator associated pneumonia, catheter infections. Piperacillin-tazobactam; ceftazidime, cefoperazone, cefepime; aztreonam; ciprofloxacin, levofloxacin; and meropenem, doripenem, imipenem have good activity against Pseudomonas. In cystic fibrosis formation of biofilm is also a major contributing factor for drug resistant infection. The choice of antibiotic in empirical therapy should depend on the age, site of infection, local resistance and prior use of certain antibiotics, including broad-spectrum cephalosporins, aminoglycosides, carbapenems, fluoroquinolones and hospital culture data. Combination therapy for empiric treatment is indicated in certain high risk patients, in severe infection and it should be prompt, as delay in therapy may lead to increased mortality.

Patients with severe typhoid fever may develop typhoid encephalopathy symptoms uric acid purchase diamox 250mg without prescription, with altered consciousness symptoms questionnaire discount diamox american express, delirium medicine jokes order diamox overnight, and confusion medicine 60 buy discount diamox 250 mg on line, myelitis symptoms low blood sugar order 250mg diamox mastercard, acute cerebellar ataxia symptoms underactive thyroid order diamox with paypal, chorea, deafness, and Guillain-Barrй syndrome. Although case fatality rates may be higher with neurologic manifestations, recovery usually occurs with no sequelae. The risk for becoming a carrier is low in children (< 2% for all infected children) and increases with age. Blood cultures are positive in 40­80% of patients, depending upon the series and culture techniques used. The diagnosis can also be made by culture of stool, urine, rose spots, or duodenal contents (via string capsule). However, the sensitivity of blood cultures in diagnosing typhoid fever in many parts of the developing world is limited because widespread liberal antibiotic use may render bacteriologic confirmation difficult. Bone marrow cultures may be positive in as many as 50% of patients after as many as 5 days of antibiotics although bone marrow cultures may increase the likelihood of bacteriologic confirmation of typhoid, collection of the specimens is difficult and relatively invasive and hence not routinely practiced. Patients with typhoid fever frequently have anemia and either leukopenia or leukocytosis. Leukopenia with left shift is typically seen in adults while leukocytosis is more common in children. If observed in the 3rd week of illness, leukocytosis should prompt suspicion for intestinal perforation. Liver function test results may be deranged, but significant hepatic dysfunction is rare. Cerebrospinal fluid studies are usually normal or reveal a mild pleocytosis (< 35 cells/mm3), even in patients with neuropsychiatric symptoms. Serologic tests such as the Widal test are of limited clinical utility in endemic areas because positive results may represent previous infection. Because many false-positive and false-negative results occur, diagnosis of typhoid fever by Widal test alone is prone to error. Other relatively newer diagnostic tests using monoclonal antibodies have been developed that directly detect S. A nested polymerase chain reaction analysis using H1-d primers has been used to amplify specific genes of S. The intracellular site of Salmonella has favored the use of flouroquinolones because of the theoretical advantage. In recent years, development of increasing resistance to fluoroquinolones has resulted in more challenges. Resistance patterns have led to a shift toward the third generation cephalosporins, azithromycin and fluoroquinolones as empiric therapy for typhoid fever while awaiting the results of antimicrobial susceptibilities. With the development of fluoroquinolones resistance, third generation cephalosporins were used in treatment but sporadic reports of resistance to these antibiotics also followed. Recently, azithromycin is being used as an alternative agent for treatment of uncomplicated typhoid fever. As per the guidelines developed by Indian Academy of Pediatrics for management of enteric fever, cefixime is the rug of choice for uncomplicated typhoid and third generation parenteral cephalosporins (ceftriaxone or cefotaxime) are drug of choice for severe typhoid. Fluoroquinolones can be used in life-threatening infections resistant to other recommended antibiotics. These patterns of resistance appear to be shifting with changing pressures in antimicrobial use. Despite a steady rise in resistance in most studies, reemergence of strains susceptible to first-line antimicrobial agents, including ampicillin, chloramphenicol and cotrimoxazole, has been reported. Ceftriaxone is the best initial parenteral choice because of widespread resistance to other agents. For susceptible strains, ampicillin, trimethoprim-sulfamethoxazole and chloramphenicol have all been used successfully, and fluoroquinolones have been used extensively, even in children in endemic areas. Therapy usually is continued for 10­14 days in children, for 4­6 weeks for acute osteomyelitis and for 4 weeks for meningitis. In the developing world, Salmonella infection associated with schistosomiasis requires treatment of both infections to achieve resolution. Defervescence in typhoid fever usually requires at least 36 hours of therapy and fever can persist for 5­7 days, even with ultimately effective therapy. Azithromycin has been effective in children with strains resistant to first-line agents. Corticosteroids are used as adjunctive therapy in the presence of delirium, obtundation, stupor, coma, or shock in children with typhoid fever; a dose of 3 mg/kg dexamethasone initially, followed by 1 mg/kg every 6 hours for 48 hours, was associated with reduction of mortality from, between 35% and 55% to 10%. For patients in whom intestinal perforation develops, surgery coupled with broad-spectrum antimicrobial therapy directed at anaerobic and gram-negative enteric bacteria is indicated. The relapse rate also varies with the antibiotic used for the initial treatment, though insufficient data, but it shows least rate of relapse with azithromycin and ofloxacin high dose. Likewise, as this organism is shed through the stool, it is possible that constipation may lead to a higher load of organism within the body whereas diarrhea could be predicted to cause the opposite effect. Despite appropriate therapy, 2­4% of infected children may experience relapse after initial clinical response to treatment. The same therapy should be repeated with proper dose and duration after sending culture. In case the empiric antibiotic is not sensitive, then it should be changed to appropriate sensitive antibiotic and the total duration should be based on the antibiotic type. There is an increasing surge of the paratyphi infection and is mostly because of the infection related to the poultry products. The clinical features have an insidious onset with high rise of fever, headache, abdominal discomfort, both diarrhea and constipation and hepatosplenomegaly. Serology though not specific but in late presentation can be an evidence of diagnosing with strong clinical suspicion, particularly with rising titer. Relapse of typhoid when occurs must be treated with the same drug as before unless the sensitivity report shows a different result and is continued for 14 days. Prevention of typhoid has to be with improvement in the sanitation and good supply of drinking water. Clean water supply, education in hand-washing, and food preparation and storage are critical to reducing person-to-person transmission. Salmonella may remain viable when cooking practices prevent food from reaching a temperature greater than 150°F (65. Two safe and efficacious typhoid vaccines, the injectable Vi polysaccharide and the oral Ty21a, had been licensed but the oral vaccine due to its own limitation has not been used widely in the developing countries and is not available in India. Currently the new, improved typhoid conjugate vaccines are being tested and recently marketed in India. The Vi polysaccharide subunit vaccine was first licensed in the United States in 1994. The Vi vaccine does not elicit adequate immune responses in children aged below 2 years. Several large field trials suggest that the Vi capsular vaccine as a single 25-g dose (0. Efficacy and safety of azithromycin for uncomplicated typhoid fever: an open label non-comparative study. Factors associated with typhoid relapse in the era of multiple drug resistant strains. Re-emergence of susceptibility to conventionally used drugs among strains of Salmonella Typhi in central west India. Drug resistance patterns in Salmonella enterica subspecies enterica serotype Typhi strains isolated over a period of two decades, with special reference to ciprofloxacin and ceftriaxone. A large outbreak of typhoid fever associated with a high rate of intestinal perforation in Kasese District, Uganda, 20082009. World Health Organization: Background document: the diagnosis, prevention and treatment of typhoid fever. These organisms leading to the second presentation other than typhoid and paratyphoid are known as nontyphoidal salmonellosis. Majority of nontyphoidal salmonellae are nonhost adapted (not host-specific) and hence have the potential to affect both human and animals. Salmonella Gastroenteritis/Food Poisoning the usual presentation is fever, nausea, headache, diarrhea with abdominal pain; Salmonella diarrhea cannot be clinically differentiated from other bacterial pathogens. Symptoms of food poisoning generally develop in 12­36 hours (range 6­72 hours) after the consumption depending on the amount of inoculum and host response. Salmonella gastroenteritis is a self-limiting illness: fever subsides by 48­72 hours and diarrhea resolves by 4­10 days. The commonly affected age group is less than 5 years old with a peak between 6 months and 2 years. The disease is prevalent not only in humans but also in pet animals, livestock and poultry which act as reservoirs and continue to pose threat to humans. Studies on isolation of Salmonella from diarrhea stools in both humans and animals done in the Northeastern part of India showed that 14. Out of 13 million cases with nontyphoidal salmonellosis reported worldwide, about 70% are reported from three countries, India, China and Pakistan. Many of the Salmonella strains are also developing resistance to common antimicrobials. Salmonella Bacteremia Bacteremia is a serious complication of Salmonella infection and believed to occur in 1­5% of the children with Salmonella diarrhea. Unlike in adults where 90% had underlying predisposing factors, majority of the children with Salmonella bacteremia were previously healthy. The infection may spread to various organs resulting in arthritis, osteomyelitis, pneumonia, endocarditis, mycotic aneurysm and meningitis. Clinical Presentation Predominant features of Salmonella bacteremia are fever, tachypnea and diarrhea. Out of 229 children with Salmonella bacteremia, 69% had respiratory symptoms and diarrhea. In children, 75% of the bacteremia were secondary to gastroenteritis and there was no death. However, in majority of the adults, bacteremia was primary and mortality was high amounting to 33%. In a retrospective study done in a pediatric hospital, 12 out of 144 children with bacteremia developed focal infection as complication. The vehicles of transmission are food products of animal origin, like poultry, beef, eggs and dairy products. Other vehicles implicated are: vegetarian products contaminated with infected human or animal source, such as fruits, vegetables, peanut butter, frozen pot pies, powdered infant formulas, cereals and bakery products Table 2). Predisposing factors for the development of salmonella infections are listed in Table 3. Salmonella Meningitis this is more commonly seen in neonates and infants, and more than three-fourths of the children affected were less than 1-year-old in most of the studies. Presence of blood in the stools usually favors the diagnosis of enterohemorrhagic E. In cases of suspected food poisoning, consumption of the food item is related to an individual or group of individuals, and time of onset of symptoms will be helpful to arrive at a diagnosis. In staphylococcal food poisoning, symptoms develop within 6 hours, but in Salmonella, the time gap will be a little later than 12­36 hours. Stool culture is preferable in comparison with rectal swab because of higher specificity and sensitivity. Other investigations such as imaging of bone or joint with bone scan are needed when child develops arthritis or osteomyelitis. Neuroimaging is a useful tool to identify the acute complications, such as subdural effusion, empyema, ventriculitis, hydrocephalus, abscess and intracranial hemorrhage. Antibiotic therapy is not warranted in an uncomplicated child with Salmonella diarrhea and is rather supposed to prolong the duration of illness and fecal excretion rate. In areas with high rate of antimicrobial resistance, third-generation cephalosporins and fluoroquinolones are the preferred choice. They do not cause colonization or disease in animals and are transmitted via fecal contaminated water or food items from an acutely affected human. Nontyphoidal Salmonella this disease predominantly presents as diarrheal disease following consumption of food contaminated by animal or human fecal material. These organisms are nonadapted and hence cause diseases in human as well as animals. Salmonella Bacteremia When Salmonella sepsis is suspected, infants less than 3 months and children with stool culture positivity should be hospitalized. Evaluation should be done to identify focal infections, like meningitis, osteomyelitis or arthritis. For invasive but nonfocal infection like bacteremia, usually the initial antibiotic is thirdgeneration cephalosporin or quinolone for a period of 14 days. Most of the papers published prior to 2,000 showed poor outcome and high morbidity when these patients were treated with chloramphenicol and ampicillin. Availability of third-generation cephalosporins and fluoroquinolones has changed the outcome because of their higher efficacy. These are rare causes of meningitis, constituting less than 1% of all causes of meningitis in neonates and infants. Both acute and chronic complications like neurodevelopmental sequelae, such as paralysis, deafness, seizures, visual disturbances and mental retardation are also more commonly encountered. It is more commonly suspected if the mother has suffered earlier from a salmonella infection and she remains as a carrier. Salmonella Meningitis the ideal empirical antibiotic therapy in salmonella meningitis is ceftriaxone or cefotaxime alone or with a combination of third 1178 generation along with quinolones.

About three-fourths of children with Autism have global developmental delay or intellectual disability medications zetia cheap diamox 250 mg fast delivery. The onset of epilepsy in autism has two peaks: first before 5 years of age and another in adolescence treatment plan for depression order generic diamox online. The type of seizures and the response to treatment are almost same as in general population medicine 93 diamox 250mg online. They often have frequent awakenings at night treatment centers for depression cheap 250mg diamox with amex, delayed sleep time treatment 2 prostate cancer buy diamox american express, prolonged sleep latency and early wake up time medications not to take during pregnancy cheap diamox 250 mg free shipping. Others demonstrate excessive fear to certain harmless objects or stimuli like soft toys, some particular people or images. These children may have started speaking few words with meanings, enjoying social play like peek-a-boo and started pointing. Subsequently regression occurs with gradual loss of speech and development of poor eye contact, social aloofness, and motor stereotypes. Many of these children with apparently normal development prior to regression actually have mild delay in social milestones from the beginning. In second and third year of life, most of the children present with delayed speech, hyperactivity or severe tantrums. They may also have poor eye contact, preference for aloofness, decreased interest in peers, poor response to being called and motor stereotypies. Expressive Language Disorder this condition is quite common and presents with speech delay. However, their receptive speech, nonverbal communication and social skills are normal. Hearing Impairment Children with hearing impairment also present with speech delay, however their nonverbal communication and social skills are appropriate for age. These children may also have impaired peer interaction, self-stimulatory behaviors and impaired gesture use. Children with impairment in only social communication and social interaction, in the absence of repetitive or restricted pattern of behaviors or interests are given this diagnosis. Emphasis is laid on the early development of social behaviors and communication skills. Other important histories include that of associated problems or comorbidities, birth history, family history and developmental history pertaining to all developmental domains. A detailed observation of the child is performed for his behavior and interaction with parents, peers, strangers and the examiners. It consists of 93 questions and is suitable for children above the mental age of 18 months. An individual is evaluated on any one module based on his age, language and developmental level. In each module, a protocol of activities or social presses is administered in approximately 45 minutes and each item is scored on 4-point scale. Schizophrenia Childhood schizophrenia is quite a rare entity, usually manifesting after 10 years of age. However, there is always a period of normal development before the onset of symptoms and hallucinations and delusions are characteristically present. Selective Mutism these children have normal speech but do not speak in particular situations or contexts. Like all screening tools, these tools also have false negatives and false positives results. A child who fails on any 3 items or 2 critical items (out ofthe6criticalitems)needsfurtherevaluation. Evaluation by a speech therapist is required for assessment of receptive and expressive level of speech, nonverbal communication and presence of stereotypic or idiosyncratic use of language. Classroom teaching is done using visual schedules to guide the child for doing activities, which are determined by the likes of the child. American Academy of Pediatrics have given recommendations for testing, however the degree of evaluation depends on the available resources. Magnetic resonance imaging should be considered in children with regression, microcephaly, midline facial defect, neurocutaneous stigmata or abnormalities on neurological examination. Metabolic testing should only be considered in children with features suggestive of inborn errors of metabolism. Over the years, many different techniques of educational interventional therapies have evolved. These comorbid symptoms often limit the functional abilities of the child and interfere with implementation of the early behavioral intervention program. Maladaptive behaviors like aggression including self directed aggression, irritability, temper tantrums and hyperactivity are common targets of pharmacotherapy. Psychotropic drugs like haloperidol, risperidone, olanzapine and aripiprazole have shown moderate to large short-term benefits in controlling these behaviors. Haloperidol, although as effective as risperidone, is less often used because of the extrapyramidal side effects. It is associated with lesser weight gain and decreased risk of hyperprolactinemia. Sleep problems is another comorbidity that can be managed using Melatonin, however it has moderate effect in reducing sleep latency and night-time awakenings and increasing total sleep duration. Other drugs used in management of sleep problems include Risperidone, Mirtazapine and Clonidine. Subsequently, there is relative flattening in gains though repetitive and maladaptive behaviors continue to improve even in adolescents and adults. Thus, all the behaviors (actions) of the child are analyzed in detail regarding their antecedents and the consequences, for determining the function of each behavior. After this analysis, the intervention program is designed to increase or decrease any particular behavior by modifying the antecedents or consequences. Autism spectrum disorder is characterized by persistent deficits in social communication and social interaction, and the presence of repetitive, restricted pattern of behaviors, interests and activities. Pharmacological agents, mainly atypical antipsychotics are used to control maladaptive behaviors. Clinical assessment and management of toddlers with suspected autism spectrum disorder: insights from studies of high-risk infants. They usually survive into adulthood, but the incidence of sudden, unexplained death is significantly higher. Functioning as a global transcriptional repressor, mutations in this gene produce loss of function of this protein and unregulated expression of the other genes that it normally represses. However,recurrencein families can occur through mechanisms such as germline mosaicism. The girls develop autistic features with poor eye contact, solitary play and characteristic midline hand stereotypies (washing, clapping, tapping, wringing, hand mouthing, hair pulling, pin rolling, clenching, clapping), preceded by loss of purposeful fine motor skills. There is gait apraxia with ataxia and evolving spasticity of limbs, breathing abnormalities in the form of episodic hyperventilation, apnea, aerophagy and valsalva maneuver and development of seizures. This phase may last for few weeks to months and is followed by 3rd phase, Pseudostationary stage, starting from 2 years to 10 years of age. This stage is characterized by improvement in socialization, eye contact, nonverbal communication skills and some gain in gross motor milestones with achievement of locomotion. Seizures may appear for the first time during this phase but stereotypies may decrease later. Progressive scoliosis usually appears after 10 years of age, is believed to be neurogenic and is more marked in those with more severe developmental impairment. The cause is unclear but may be related to seizures, autonomic dysfunction, or cardiac conduction abnormalities,e. Girls with classical presentation have an uneventful preperinatal period with a normal head circumference at birth and no dysmorphic facies. First few months are grossly normal, with development of some speech and hand functions. Though decrease in head size may start from 4 months onward and there may be some subtle features, none are severe enough to raise concerns by the family or the pediatrician. The onset is usually heralded by sudden onset irritability marked by episodes of excessive crying, self injurious Differential Diagnosis Stage I (Early Onset Stagnation) Benign congenital hypotonia, cerebral palsy, Prader-Willi syndrome, Angelman syndrome and other metabolic disorders are important conditions to be considered during this phase. Comprehensive management also includes physical rehabilitation, educational as well as psychosocial support and is best provided by a team. Physiotherapy, occupational therapy and adaptive technologies have been found effective in facilitating communication, maintaining hand function and locomotion. Progression of scoliosis and the ability to walk can be managed by intensive physical therapies. Adaptive equipments like braces and arm splints have also been found very effective. Psychosocial support for families is an integral part of the holistic approach to management, and parent support groups offer immense practical day-to-day support to families. Rett syndrome is a neurodevelopmental disorder usually seen in females but has also been diagnosed in some males. The common atypical variants are: (i) preserved speech variant, (ii) congenital variant and (iii) an early seizure variant. The rapid destructive stage is the most characteristic period and is characterized by loss of purposeful hand movements followed by distinctive midline, compulsive hand stereotypies. There is also loss of motor, communication and social skills with poor eye contact and decreased interaction, gait ataxia, seizures, breathing problems and sleep problems. Evaluation of current pharmacological treatment options in the management of Rett syndrome: from the present to future therapeutic alternatives. Impairment in academic and social functioning along with skill deficits render such children to academic failures and social isolation leading to demoralization, poor self-esteem, delinquency and substance use. Its inheritance is complex and is modulated by environmental factors with genetics playing a major role. The lack of an objective test makes the behavioral features and the resulting dysfunction as an important tool to diagnose the condition, which is complicated by the frequent presence of coexisting psychiatric disorders. Pharmacological treatment needs to be appended with psychosocial interventions, such as parent training and cognitive behavior therapy, for management. Twinstudieshave observed higher concordance rates in monozygotic compared to dizygotic twins. Dorsal striatum modulates responses and the cerebellum coordinates motor activities and attention. Response inhibition delays and interrupts responses and controls interference for controlling verbal and motor impulses. The nonverbal and verbal working memories govern the capacity for reading comprehension and moral conduct. Working memories also provide the ability to control emotions along with the motivation and persistence necessary to meet goals. Analysis of experiences in order to synthesize new responses for achieving goal is undertaken by reconstitution. The Indian Council of Medical Research reported prevalence rate of hyperkinetic disorders to be 1. Stimulus processing research has showed deficits in early as well as later processing. Structural Neuroimaging Decrease in overall total brain size is the most consistent finding being reported. The disorder does not meet the criteria for pervasive developmental disorder, mania, depressive, or anxiety disorder. Specify if: Disturbance of activity and attention: the general criteria for hyperkinetic disorder must be met, but not those for conduct disorders. Hyperkinetic conduct disorder: Both the general criteria for hyperkinetic disorder and conduct disorder must be met. Other hyperkinetic disorders Hyperkinetic disorder, unspecified: this residual category is not recommended and should be used only when there is a lack of differentiation between disturbance of activity and attention and hyperkinetic conduct disorder but the overall criteria for hyperkinetic disorders are fulfilled. The symptoms suggestive of the disorder need to be present in two or more setting (at home, at school, during play, in social gatherings, etc. The symptoms may secondarily dispose a child towards difficulty in forming friendships, peer rejection, poor self-esteem, and increased risk for depression and anxiety. It is essential to differentiate from subtle aberrant behavior which may usually be present in normally developing children not having any impairment like short attention span in a preschool child or occasional impulsivity in a school going child. Medical Evaluation An evaluation of child and family cardiac history, dietary history and daily sleep pattern should be undertaken before initiating medications. The physical examination including a complete neurological examination should be undertaken. Regular monitoring of vital signs, height, weight and head circumference aids in assessment of medication effects. The difficulty in collecting information may arise in situations of parental denial, minimization, manipulation, rationalization or contradictory views. Open-ended questions or questionnaires may be utilized to acquire historical information regarding symptoms. Behavior rating scales Scales are useful for acquiring structured information of behavior, estimating symptom severity, measure treatment response and may add to the validity of the diagnosis. They can help to recognize comorbid conditions and make the differential diagnosis narrow. Psychosocial evaluation It is prudent to assess the impact of symptoms on the psychosocial environment and vice versa which may provide an alternative explanation for the symptoms. Neuropsychological testing It may be valuable in assessing coexisting conditions (like learning disabilities), excluding other disorders, planning interventions, and charting treatment progress. The evaluation comprises of medical, developmental, behavioral, educational and psychosocial perspectives. Common coexisting conditions reported in Indian literature are developmental delays, temper-tantrums, enuresis, tics, parental discord and parental psychiatric illness. After the complete evaluation, a thorough discussion of the clinician with the parents is recommended regarding the child problematic behavior with its appropriate management measures which may entail implementing a daily report card procedure prior to initiating a medication trial or other psychosocial intervention. The Childhood Years Second-line agents (off label drugs) include antidepressants such as bupropion, venlafaxine and tricyclic antidepressants particularly desipramine, nortriptyline and imipramine.

The usefulness of cooling may be reduced if there is a high incidence of pre-existing brain damage or if the therapeutic window has elapsed medications enlarged prostate generic diamox 250 mg free shipping. By the time the neonates are admitted in the neonatal unit treatment uveitis purchase 250 mg diamox with mastercard, the secondary surge of neuronal death related to secondary energy failure may have already happened medications in carry on luggage order 250 mg diamox otc. Perinatal asphyxia may also coexist with neonatal sepsis symptoms rheumatic fever cheap diamox 250mg without prescription, and it may be challenging to differentiate both the conditions at birth symptoms of anxiety discount diamox online. Exclusion of infected infants is unlikely to be realistic and core temperature reduction may result in neutrophil compromise medications metabolized by cyp2d6 purchase genuine diamox online, which can worsen sepsis and pneumonia. This may partially explain the relationship between hypothermia and neonatal death in developing countries. Accidental hypothermia is witnessed in many asphyxiated infants in developing countries due to a number of factors including home birth, lack of basic neonatal care and overhead radiant warmers. Excessive cooling or overcooling is commonly associated with inadequately controlled cooling which usually happens during transport of very ill asphyxiated infants. Troponin-T and troponin-I are sensitive markers of myocardial injury following a perinatal hypoxic ischemic insult and may help predict severity of neonatal hypoxic ischemia and mortality. Infants who do not progress to Sarnat stage 3 and who have clinical signs of moderate encephalopathy for less than 5 days generally have a normal outcome. Neurological Problems of the Newborn Infant Newer Therapies the understanding of the differential responses to hypoxiaischemia as an initial insult leading to cellular degeneration in brain has opened the way to develop new pharmacologic and therapeutic approaches. Due to the complex pathophysiology, therapies can target early pathways such as oxidative stress, inflammation and apoptosis or delayed pathways such as the deprivation of growth factors and cell death. Pharmacological interventions should start at different points of time according to their mechanisms of action Table 9). The association of moderate hypothermia with neuroprotective drugs may decrease cell injury and optimize endogenous repair. Hypoxic ischemic encephalopathy is a complex process evolving over hours to days providing a unique window of opportunity for neuroprotective treatment interventions. Therapeutic hypothermia using gel packs for term neonates with hypoxic ischemic encephalopathy in resource-limited settings: a randomized controlled trial. Hypothermia for perinatal brain hypoxia-ischemia in different resource settings: a systematic review. Effect of therapeutic hypothermia on oxidative stress and outcome in term neonates with perinatal asphyxia: a randomized controlled trial. New pharmacologic and therapeutic approaches for hypoxic-ischemic encephalopathy in the newborn. Brain injury following whole body cooling after neonatal encephalopathy in a south Indian neonatal unit. The vascular system in preterm infants is fragile due to an immature support structure. The support structure consists of endothelial tight junctions, astrocyte end-feet, basement membrane and pericytes. Pericytes provide structural integrity to the capillaries, venules, and arterioles. In addition, impaired autoregulation of cerebral blood flow leads to a pressure passive state and altered flow. The areas commonly affected by focal necrosis are around the foramen of Monro and the peritrigonal area of the lateral ventricles. The Injury Focal injury can be macroscopic or microscopic necrosis in the deep periventricular white matter. This injury results in not only a decrease in number of surviving preoligodendroglial cells but also a maturational arrest in the remaining cells due to accumulation of hyaluronic acid. Thus, these remaining cells do not mature effectively into myelin producing oligodendroglial cells thereby affecting neuronal signaling. Axonal growth is prominent in the premature period and mature oligodendrocytes are necessary for effective axonal growth and connectivity. The arterial supply is from the main branches of the anterior cerebral artery, middle cerebral artery, and anterior choroidal artery. The terminal branches near the germinal matrix are in a watershed zone predisposing it to ischemic or reperfusion injury. During early gestation, the network is fragile with thin, delicate, and immature walls without the support of a basement membrane. The preterm neonate has limited ability in autoregulating cerebral blood flow producing a pressure passive state. A change in systemic blood pressure directly leads to alteration in cerebral blood flow. Lack of blood flow in the immature germinal matrix vessels leads to cell death, breakdown of the vessel wall, and eventual bleeding. Ventricular blood flows through the drainage system reaching the foramina of Magendie and Luschka and collecting in the basilar cisterns in the posterior fossa. Clot formation most often occurs at the aqueduct of Sylvius near the level of the arachnoid villi. The vascular network supplying the germinal matrix is continuous with a well-developed venous system. The smaller tributaries drain into the terminal vein, coursing alongside the germinal matrix terminating in the vein of Galen. As the ventricle fills with blood or clot, the venous drainage of the periventricular parenchyma is impeded resulting in venous congestion. Many of the pathogenic factors seen in preterm infants also apply to term infants. Three causes seen primarily in term infants are: (1) birth trauma, (2) coagulopathy, and (3) cerebral sinovenous thrombosis. Currently, the leading theory relates to factors that increase cerebral venous pressure. They are located deep in the periventricular region and are particularly vulnerable to hypoxic ischemic injury. Similar to the arterial supply of the germinal matrix, the vessels branch primarily from the middle cerebral artery with minor contribution from the anterior and posterior cerebral artery. Active periventricular vascular growth and development occur between 24 weeks and 34 weeks of gestational age. Thus, preterm neonates are at risk for injury due to the immaturity in vasculature. Microglia are abundant in cerebral white matter and particularly susceptible to ischemia. During the reperfusion phase, they produce free radicals and cytokines that lead to further injury. Maturing oligodendrocytes are sensitive to injury from free radicals leading to cell death. Inflammation due to maternal intrauterine infection or postnatal sepsis is also a pathogenic mechanism that can coexist with ischemia Table 1). If preterm delivery is unavoidable, the route and location of delivery may have an impact. As an adaptive mechanism, cerebral blood flow increases to maintain cerebral oxygen delivery in an anemic neonate. It is often detected on a screening head ultrasound on the first or second day of life. Possible clues may be a failure of the hematocrit to rise after a packed red blood cell transfusion. Signs will gradually appear over days consisting of increased ventilator settings, mild acidosis on a blood gas, or hyperglycemia. The neonate may have bradycardia, hypotension, temperature fluctuations, pallor and poor perfusion, a tense bulging fontanel or severe hypotonia. In term infants, clinical presentation can range from the first few days of life to a month of life. When there is associated neuronal or axonal injury, a wide spectrum of clinical deficiencies can develop from impairment in intelligence to falling on the spectrum of autistic disorders. Prior to discharge, increased appendicular tone, hyperreflexia, and ankle clonus consistent with upper motor neuron injury may be seen. Episodes of apnea and desaturation could point toward apnea of prematurity, gastroesophageal reflux, sepsis, necrotizing enterocolitis, or a central nervous system disorder. Electrolyte abnormalities such as hyperglycemia and metabolic acidosis could be secondary to sepsis or necrotizing enterocolitis. Physical exam findings of poor perfusion, lethargy or pallor could indicate sepsis. It is a low-cost noninvasive bedside test that is easy to perform in a busy intensive care unit and produces high-resolution images without ionizing radiation. Using the open anterior fontanel, one is able to visualize the ventricles and surrounding parenchyma. More recently, an updated classification system developed by Volpe takes into account the percentage of ventricle filling by the bleed. Monitoring electrolyte levels, respiratory mechanics and hemodynamic status are a few measures to play close attention to . In the catastrophic presentation, resuscitation including intubation, volume expansion, and inotropic medication for abrupt hemodynamic change, and chest compressions may be needed to stabilize the critically ill neonate. Clinical features, such as a bulging fontanel, diastasis of the sutures and increase in head size, do not present for weeks after ventricular dilatation due to the higher water content and compressibility of the preterm brain and the large subarachnoid space. Intraparenchymal blood can irritate the surrounding cortical tissue leading to seizure activity. Early diagnosis and treatment of seizure activity in the neonate may impact longterm neurodevelopmental outcome. Destruction of developing oligodendrocytes leading to impairment of myelination affects the long-term outcome. The corticospinal tracts pass through the periventricular region with the lower extremity bundles most adjacent to the lateral ventricles. Specifically, cognitive and psychomotor delay, cerebral palsy and neurosensory impairment are common. Steroids are well documented to accelerate the maturity of the brain, improving the pressure passive state. There is some evidence that magnesium sulfate is able to neutralize reactive oxygen species and enhances the preterm antioxidant system. Specifically, the greatest reduction occurred in male preterm neonates less than 25 weeks of gestational age. Animal studies and postmortem autopsies of preterm infants have shown indomethacin increases key components of the basal lamina improving structural integrity of the germinal matrix vasculature. Muscle paralysis and sedation has been shown to improve the fluctuation in cerebral blood flow in preterm neonates requiring mechanical ventilation. However, there are risks that go hand in hand that need to be considered when deciding to use paralytics and sedation in this population. White matter injury can be focal or diffuse and microscopic (more common) or macroscopic (cystic). Finally, ongoing research on the use of free radical scavengers in preventing oligodendrocyte injury could potentially improve neurodevelopmental outcomes in preterm neonates at risk. Intraventricular hemorrhage and neurodevelopmental outcomes in extreme preterm infants. Intraventricular hemorrhage spectrum in premature neonates: evidence based neuroimaging. Understanding brain injury and neurodevelopmental disabilities in the preterm infant: the evolving role of advanced magnetic resonance imaging. Predictors of mortality and major morbidities in extremely low birthweight neonates. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. The etiology may be diverse but the basic supportive measures include oxygen and ventilator support when distress is severe. It is, therefore, important to be able to assess severity of respiratory distress to decide the treatment modality. It is equally important to be able to determine the etiology as treatment varies from simple supportive measures to surgery if the cause of distress is surgical. This section will deal with clinical approach to respiratory distress in neonates to help determine etiology and assess severity. Table 3 summarizes the cardiac conditions that can cause respiratory distress in neonates. One must suspect cardiac cause, if there are malformations, cyanosis, hepatomegaly or shock. Identifying these conditions is important as duct-dependent lesions will need immediate treatment with prostaglandins. Priority is to assess the severity and decide regarding need for immediate intervention. This should be followed by a detailed history and examination to determine etiology. These include respiratory distress syndrome, meconium aspiration syndrome, pneumonia, pneumothorax and persistent pulmonary hypertension of newborn. This table also highlights the time of onset of respiratory distress in each of these conditions. Particularly, conditions such as primary surfactant deficiency, primary ciliary dyskinesia are rare causes.

Buy 250 mg diamox with amex. Endocarditis Nursing Pathophysiology Treatment | Infective Endocarditis Lecture.