Piero Anversa, MD

• Departments of Anaesthesia and Medicine
• Center for Regenerative Medicine
• Brigham and Women? Hospital
• Harvard Medical School
• Boston, MA

The changes in intrabronchial and extrabronchial reactivity were strongly associated with pharyngitis fungus gnats bti cheap nizoral 200 mg otc, as determined by history antifungal shampoo for cats nizoral 200mg cheap, physical examination fungus feet buy nizoral 200mg line, and nasal lavage fluid analysis anti fungal wash b&q generic nizoral 200 mg. The investigators proposed that airway hyperresponsiveness in rhinosinusitis might depend on pharyngobranchial reflexes triggered by the postnasal drip of A fungus identification proven 200mg nizoral. It has been hypothesized that inflamed sinus tissue not only releases mediators and cytokines into the circulation fungus zucchini plants discount 200mg nizoral mastercard, thereby directly inducing inflammation of the upper airway, but also releases chemotactic factors that recruit eosinophils from the bone marrow and from the circulation into the upper and lower airways. It is characterized by increased eosinophilic inflammation and formation of IgE antibodies to staphylococcal exotoxins. Two uncontrolled observational studies in children with combined infectious rhinosinusitis and asthma showed significant improvement in the asthmatic state, including pulmonary function, when rhinosinusitis was medically treated. Overall, asthma control improved significantly after the 2 treatment modalities but was better maintained after medical therapy. Further research is required to establish the relations between the upper and lower airways. The panel recommended re-evaluation as necessary and antibiotics if there was worsening or no improvement with symptomatic therapy. This review did not make recommendations for pediatric patients, patients with suppressed immune system, and patients with severe disease. Minor adverse effects such as epistaxis, headache, and nasal itching were reported in these studies. A recent randomized, double-blinded, placebo-controlled trial comparing 30 mg/d of prednisolone or placebo for 7 days did not find systemic corticosteroid monotherapy to be superior to placebo. However, they also noted that the data are limited and there was a significant risk of bias. Antihistamines may slightly alleviate rhinorrhea and sneezing, but the overall benefit is minimal. Decongestants decrease congestion over 6 to 10 hours, but there is no evidence to suggest benefit for longer than 10 hours. Topical decongestants, when used for a short period, are of benefit in decreasing congestion but can lead to rebound congestion if used for a longer term. Nasal irrigation with saline is often used as adjunct treatment of rhinosinusitis, but the evidence is limited. Clinical trials that specifically attempt to eradicate pathogens or that document sterilization of sinus cavities are very limited. Eradication of infection also depends greatly on whether sinus aeration and adequate mucociliary clearance can be restored. For patients with persistent purulence despite previous antibiotics, obtaining a sinus culture is strongly recommended. Short-term treatment trials are defined as those no longer than 4 weeks in duration. No significant differences in outcomes were noted in cefaclor- vs amoxicillin-treated patients. In a study by Legent et al,284 amoxicillin-clavulanate was compared with ciprofloxacin. Treatment lasted only 9 days; however, patients were evaluated 40 days after treatment. Similar clinical cure and bacteriologic eradication rates were found for the 2 treatments; however, in patients who had a positive initial culture and who were evaluated 40 days after treatment, ciprofloxacin had a higher cure rate (83. The bacteriologic cure rates, defined as eradication of the original pathogen with or without recolonization with nonpathogenic flora, were similar for the 2 treatments, although relapses were more frequent in cefuroxime-treated patients. Improvement in the Lund-Mackay score was noted after comparing baseline with week 6 (8. Van Zele et al291 conducted a randomized, double-blinded, placebo-controlled trial to assess whether doxycycline could decrease nasal polyp size and provide anti-inflammatory effects. Doxycycline (200 mg on the first day followed by 100 mg once daily for 20 days) caused a small but statistically significant decrease in polyp size beginning at week 2 and persisting for 12 weeks. All patients received an initial 6 weeks of medical treatment and only patients remaining symptomatic after this treatment were randomized into the study. The study by Wallwork et al295 was a randomized, placebocontrolled investigation of 150 mg/d of roxithromycin vs placebo for 12 weeks. Patients in the roxithromycin group showed a statistically significant change from baseline in Sino-Nasal Outcome Test-20 score at 12 weeks, which was not seen in the placebo group. Multiple clinical assessment tools were used, including symptom scoring, the Short Form-36, rigid nasal endoscopy, peak nasal inspiratory flow, and endoscopically guided middle meatus cultures. Most topical antibiotic studies have involved administration of nebulized antibiotic for 3 to 6 weeks in prospective observational studies only rather than double-blinded or placebo-controlled studies. Endoscopic improvement and an increase in infectionfree interval after treatment were reported in another study. Twice-daily irrigation with gentamicin for 3 to 15 weeks caused low but measurable systemic absorption, with blood levels ranging from 0. In an observational cohort, Anand et al303 reported improvement in symptom scores; however, the study was underpowered and no comparator group was included. Thirty-six of the 40 patients showed symptomatic and/or radiographic improvement after the medical regimen. Patients with aspirin-exacerbated respiratory disease in whom aspirin desensitization should be considered include those who have suboptimal control with currently available pharmacologic therapy, those who have required multiple polyp removal surgeries, those who require frequent or daily systemic steroids to control nasal or asthma symptoms, and those who require aspirin or other nonsteroidal anti-inflammatory drugs for other coexisting disease, such as cardiovascular disease or arthritis. Contraindications to aspirin desensitization include pregnancy, unstable asthma, gastric ulcers, and bleeding disorders. Inpatient desensitization also should be used for patients with risk factors such as recent myocardial infarction or b-blocker use. If the procedure is performed over 2 days, the first dose given on day 2 should be the highest tolerated dose the patient received on day 1. Intravenous access, emergency resuscitation equipment (including nebulized b-agonists and intramuscular epinephrine), and medical supervision also should be present. Some patients may require only 325 mg twice or once a day to maintain improvement. If the need for higher-dose aspirin or another nonsteroidal antiinflammatory drug is likely, continue maintenance with at least 325 mg/d. In contrast, atopy, asthma, and persistent obstruction of the ostiomeatal unit were not associated with early relapse. The highest level of evidence comes from a prospective case series308 and a recently published double-blinded, placebocontrolled trial in children. Treatment usually results in clinical improvement and transient improvement in sense of smell, although the duration of clinical benefit is variable and may decrease with repeated courses (expert opinion). A meta-analysis of 5 published studies was reported in the European Position Paper on rhinosinusitis and nasal polyps 2012 document. These studies compared topical corticosteroid treatment with placebo, not with intranasal treatment. Prepare 5-mg/mL mixture of water and Alka-Seltzer Protocold Cumulative time (h) 0 1e 2. The patient is advised to completely avoid cyclooxygenase-1 inhibitors or to consider aspirin desensitization and continuous aspirin therapy. The patient should understand that there may be a severe exacerbation of asthma, and that if aspirin is stopped for longer than 48 hours, the desensitization procedure will need to be repeated. After the patient is completely stabilized (but not <3 hours after the last dose), the provoking dose can be repeated. If nasal, gastrointestinal, or cutaneous reactions occur on day 1, pretreat with histamine-1 and histamine-2 receptor antagonists for the remainder of the procedure. After successful desensitization, the patient should continue taking 650 mg twice daily, but tapering of the dose can be attempted if the patient is doing well 6 months after desensitization. Some patients may require only 325 mg twice or once a day to maintain their improvement. If the need for higher-dose aspirin or another nonsteroidal anti-inflammatory drug is likely, continue maintenance with at least 325 mg/d. Topical decongestants can be considered for short-term and possibly for intermittent or episodic therapy of nasal congestion but are inappropriate for regular daily use because of the risk of development of rhinitis medicamentosa. In the study by Aukema et al,334 topically delivered fluticasone propionate was superior to placebo at improving disease-specific symptoms and grading of nasal polyp severity using a visual analog scale score. The duration of this study was 12 weeks, and treatment was unassociated with significant systemic toxicity. Treatment with fluticasone propionate nasal drops was associated a decreased need for sinus surgery (from 78% to 52%). Naegleria fowleri, present in unboiled or otherwise unsterilized water, causes the fatal brain infection primary amoebic meningoencephalitis. Studies have suggested that squeeze bottles may provide the best delivery to sinuses and are superior to saline sprays, nebulizers, or low-pressure devices, such as the Neti pot. Leukotriene-modifier drugs are useful to help protect against significant aspirin-induced bronchospasm during aspirin desensitization. This procedure consists of administration of incremental oral doses of aspirin over 1 to 2 days until a dose of 650 mg of aspirin can be taken without adverse reaction (Tables 6, 7). The procedure requires frequent monitoring with spirometry in an observational setting with trained staff. This protocol decreased the duration of the desensitization process and was safer compared with standard oral aspirin desensitization protocols. Aspirin desensitization therapy improves clinical outcomes for upper and lower respiratory tract disease. In addition, improvements in asthma symptom scores and sinus disease and symptoms including sense of smell have been noted. During long-term aspirin desensitization, urinary leukotriene E4 is lowered to baseline levels, leukotriene C4 and histamine in nasal secretions disappear, bronchial responsiveness to leukotriene E4 is greatly decreased, and cysteinyl leukotriene receptor-I expression decreases on respiratory cells. This addition resulted not only in alleviation of asthma but also in return of smell, less rhinorrhea, and a trend toward less stuffiness and greater nasal inspiratory flow. In this study, nasal polyp score was only significantly decreased in the 1-mg/kg reslizumab treatment group at week 12. In contrast, peripheral blood eosinophil numbers and concentrations of eosinophil cationic protein in serum and nasal secretions were decreased up to 8 weeks in the 2 active treatment arms. Individual nasal polyp scores improved in only 50% of treated patients for 4 weeks ("responders"). Omalizumab treatment was associated with a significant decrease in total nasal endoscopic polyp scores after 16 weeks compared with placebo. The middle meatus and the ethmoid sinuses were recognized as important factors in the persistence of frontal and maxillary sinusitis. During surgery, significant attention should be paid to mucoperiosteal preservation and the avoidance of bone exposure to minimize the risk of delayed healing and improve ciliary regeneration. It is important that patients with environmental allergies and environmental exposures have these controlled in conjunction with surgical intervention whenever this is possible. Surgical intervention exposes virgin mucosa to nasal airflow and thus potentially allows initiation of the inflammatory process at a new site. Although there has been some controversy about the influence of continued smoking after surgical intervention, at least 1 study has indicated that this is a major factor in persistent disease. Because the radiographic and endoscopic appearance of unilateral polypoid disease may frequently be the result of fungal disease or tumor (eg, inverted papilloma), biopsy examination should be considered in these patients. Given the markedly improved safety of general anesthesia and rapid recovery after total intravenous anesthesia, endoscopic sinus surgery is typically performed Table 10 Indications for surgical intervention When nasal polyps obstruct sinus drainage or cause significant nasal congestion and persist despite appropriate medical treatment When there is recurrent or persistent infectious rhinosinusitis despite adequate trials of medical management that at least includes topical nasal steroids and nasal irrigations; in many cases, 1 course of antibiotics is required, chosen to cover the spectrum of pathogens anticipated to be causing the disease, and a course of oral steroids may be considered if there is no contraindication For biopsy of sinonasal tissue to rule out granulomatous disease, neoplasm, ciliary dyskinesia, or fungal infections When maxillary antral puncture is required (eg, as for culture-directed therapy) When anatomic defects obstruct the sinus outflow tract, particularly the ostiomeatal complex (and adenoidal tissues in children) For rhinosinusitis with threatened complications (eg, threat of brain abscess, meningitis, cavernous sinus thrombosis, or frontal bone osteomyelitis) A. In most cases, surgery is performed on an outpatient basis, but patients with significant underlying medical conditions may require overnight observation. Endoscopic surgical procedures are carried out through the nostril under endoscopic visualization and do not involve external incisions. There are different opinions regarding the extent of surgery that should be performed, ranging from a very minimal procedure or balloon dilatation of the affected ostia, to very complete opening of all the sinuses. However, the standard teaching for the functional endoscopic approach is that the surgical procedure should extend beyond the margins of the ostiomeatal disease and the inflamed boney partitions should be removed. Although symptomatic improvement from balloon dilation has been well documented, in general, patients selected for this approach have only minor disease, a significant proportion of which might be amenable to medical therapy alone. Conclusions regarding long-term resolution of disease with minimal interventional approaches remain unproved. With endoscopic sinus surgery, postoperative pain after surgery is typically minimal, and early symptom improvement is generally the rule. However, appropriate surgical intervention requires a combination of surgery, local postoperative care, and topical and systemic medical management. In addition to removing inflamed tissue and improving sinus drainage, surgery provides access for topical therapies to control the inflammatory cascade. Balloon dilatation of the sinuses in very select cases may be a valid alternative to medical or other forms of surgical intervention. Balloon catheter technology has been validated in multiple proofof-concept studies as a feasible means to dilate sinus ostia, with improvement in subjective and objective measurements of disease compared with pretreatment baseline. Those in the balloon group also required larger numbers of antibiotic courses and office interventions during a 12 month follow-up. The hypothesis behind this approach is that moderate local concentrations of steroid introduced into the healing milieu will promote more optimal healing patterns and suppress recurrence of inflammatory disease.

Types of Ocular Movements Various types of movements occur in the eyeball that helps to visualize the object clearly by controlling the extra ocular muscles antifungal home remedy for scalp order generic nizoral line. There are four types of eye movements: saccades anti fungal shampoo buy cheap nizoral 200 mg line, smooth pursuit movements antifungal acne cream cheap 200 mg nizoral mastercard, vergence and vestibular movements fungus gnats garden order nizoral 200mg free shipping. Vergence these movements occur when an object comes near or moves far from the eye antifungal vitamins generic nizoral 200mg with visa. For example fungus gnats earth discount nizoral 200 mg mastercard, if an object comes near in the midline, both the eyeballs turn medially (convergence), and if it goes away, both eyeballs rotate laterally (divergence). So, for a single eyeball, when an object moves closer in the nasal field of vision, conver gence occurs; and when it moves closer in the temporal field of vision, divergence occurs. Saccades these are rapid, jerky movements that occur when the gaze shifts from one object to the other. Their function is to keep the new object in focus by changing the orientation of the eyeball. Thus, they prevent the adaptation of neurons in the visual pathway and reduce the strain on the extraocular muscles by bringing out the change. When the gaze is fixed on an object for longer period, the extraocular muscles remain contracted to maintain the position of the eyeball and this may lead to muscle fatigue. Vestibular Movements When the head moves, to keep the object in focus, the eyeball moves in response to stimuli arriving from the semicircular canals. Nystagmus the involuntary, rhythmical, oscillatory movement of the eyeball is known as nystagmus. Smooth Pursuit Movements these are the tracking movements of the eyes as they follow moving objects. When the gaze is fixed on a stationary object, there occur continuous contractions of a few muscle fibers 1200 Section 12: Special Senses producing minute oscillations at a rate of 3080 cycles per second. Due to these small tremorlike movements, the image constantly moves over a small area of the retina. As the same neuron does not get stimulated continu ously, the adaptation of neurons in the visual pathway is prevented. Though the stimulus first activates the photorecep tors, it is the neurons that get adapted earlier than the photoreceptors. If the image falls on the same spot of the retina, the neural discharge gradually decreases and the object disappears from view. Thus, the physiological nystagmus helps the eyes to see the object clearly for a longer duration. As the oscillations help to fix the gaze on an object, they are also called fixation movements. The eyes slowly follow the object and then quickly come back to the initial position of gaze by a rapid saccade. Recording of electrical activities of the retina by stimulating it with a flash of light is called electroretinography. With fully dilated pupil and following application of local anesthetic, it is performed by placing contact lens electrode (recording electrode) on the cornea, reference electrode on the skin of the forehead, and reference electrode over the earlobe. The awave originates from the retinal photorecep tors; the bwave originates from the bipolar cells and the cwave originates from the pigment epithe lium. It gives information about the rods located at the periph ery of the retina and their connections. It is helpful in the diagnosis of retinal detachment, retinal dystrophy, vitamin A deficiency, etc. Pathological Nystagmus In some pathological conditions, these oscillatory move ments become noticeable. Nystagmus can be due to disor ders of vestibular system or lesion of the neural pathways controlling the ocular movements. Abnormalities of Eye Movements Abnormalities of eye movements are summarized in Table 148. In case of paralysis of eye muscles, abnormali ties like diplopia, strabismus and loss of accommodation occur. So, each eye receives a little different image of the same object compared to the other. Fusion of both the images at the level of visual cortex helps to view the object as a single one, but the differ ence helps in depth perception (stereoscopic vision). It is the recording of electrical activities generated in the visual pathway from retina to the visual cor tex in response to light or pattern stimulation of the eye. A chain of waves are produced at various laten cies, out of which P100 is a large positive potential that occurs after 100 milliseconds after application of the stimulus. Abnormalities in the latency and amplitude of vari ous waveforms are helpful in the diagnosis of various diseases, like optic neuritis, optic atrophy, refractive errors, color blindness, etc. It records the effect of light and dark adaptation on the retinal resting potential generated at the pigment epithelium. The retinal resting potential is 6 mV across the pigment epithelium with the receptors side being electrically positive and the choroidal side electrically negative. The involuntary, rhythmical, oscillatory movement of the eyeball is known as nystagmus. Name the eyeball movements and the cranial nerves for that, What is physiological and pathological nystagmus, What are visual evoked potentials, What is electroretinography. Correlate the functional anatomy with functions of external, middle and inner ear. Anatomically, the ear is divided into three parts: the external (outer) ear, the middle ear and the internal (inner ear). The inner ear houses both the organ for hearing (the auditory apparatus or cochlea) and the organ for equilibrium (the vestibular apparatus). The external ear, middle ear and the cochlea of the inner ear are components of the hearing system. The vestibular apparatus consisting of the saccule, utricle and three semicircular canals is concerned with the main tenance of body equilibrium, detail mechanism of which is discussed in last chapters of motor physiology. The external onethird of the canal is cartilaginous and the internal twothird is bony. The canal contains sebaceous glands that secrete ceru men (earwax) and fine hairs that line its wall. The oily cerumen and the hairs prevent entry of dust and foreign particles into the ear. Excessive production of sebum along with lack of proper cleaning of the external meatus leads to hardening and impaction of the wax that blocks the passage and produces conduction deafness. The pinna and the external auditory canal together produce a 15 dB increase in the sound intensity due to their characteristic shape. The small portion of cartilage in front of the opening of the auditory canal is known as tragus. In humans, the pinna is fixed, but in many animals, it is mov able, and can be oriented in the direction of sound. The rim of the auricle is called the helix and the lower soft tissue portion is called the lobule. It funnels the sound waves into the auditory canal to reach the tympanic membrane. The middle ear (tympanic cavity) is a rectangular air filled compartment in the temporal bone. The anterior wall opens to the exterior via the eustachian tube at the level of the nasopharynx. The posterior wall communicates with the mastoid air cells (air cavities in the mastoid process of the tempo ral bone) through a space called the tympanic antrum. When infections of the middle ear spread to the mas toid air cells, they cause mastoiditis. The medial wall contains two small membrane covered openings (the oval window and the round window) and separates the middle ear from the inter nal ear. The lateral wall is formed by the tympanic membrane that separates the external ear from the middle ear. The roof of the middle ear is formed by tegment tym pany that separates it from the middle cranial fossa. Its inner surface is lined by mucous membrane and its outer surface is covered by skin. Though thin, it stands as a mechanical barrier and prevents the entry of foreign particles, dust and secre tions from the outer ear to the middle ear. These are three small bones, the malleus (hammer), the incus (anvil), and the stapes (stirrup). The handle of the malleus (manubrium) is attached to the internal surface of the tympanic membrane. The malleus articulates with the body of the incus that, in turn, articulates with the head of the stapes. When sound waves strike the tym panic membrane, it vibrates almost at the same fre quency as that of the sound waves. The vibrations of the membrane get transmitted to the tiny bone (malleus) attached to it. It stops vibrating soon 1204 Section 12: Special Senses through the ossicular chain and produce vibrations of the footplate of stapes, which then transmits the vibrations to the perilymph of the inner ear through oval window. In a disease called otosclerosis, there is bony fixation of the stapes to the walls of the fenestra vestibuli, resulting in severe deafness due to loss of the vibrating capacity of the stapes. The round window is present below the oval window and is enclosed by a flexible membrane called the sec ondary tympanic membrane. Improve sound transmission to the cochlea in the range of voice communication while decreasing responses to frequencies above and below this range. Eustachian Tube this connects the middle ear with the pharynx and equal izes the air pressures on both sides of the tympanic membrane. The pharyngeal end of the tube is normally closed by a valvelike mechanism, but muscle movements open it during swallowing, yawning or sneezing, and the pressure in the middle ear equili brates with the atmospheric (pharyngeal cavity) pressure (Application Box 149. During diving in water or rapid descent in a plane, the tympanic membrane is pushed in due to increased outside pressure. If the tube is blocked due to common cold, the air in the middle ear is gradually absorbed and the tympanic membrane is sucked in, causing pain and loss of hearing. The discomfort and pain in the ear due to pressure difference are relieved by swallowing saliva or air. Ossicular Muscles Stapedius and tensor tympani are two tiny skeletal muscles attached to the stapes and the malleus respectively. The tensor tympani muscle pulls the handle of the malleus inwards, thereby increasing tension of the tympanic membrane. In response to loud noise, it contracts and pulls the footplate of stapes out from the oval window, dampening the vibrations transmitted to the inner ear (Application Box 149. In paralysis of the stapedius muscle, the patient is abnormally sensitive to loud noises, known as hypera cusis. In response to a prolonged loud noise, the tensor tympani and the stapedius contract reflexively (simultaneously in both the ears), causing the outward movement of the malleus and the inward movement of the stapes. This makes the ossicular chain much closer to each other and articulation sites very tight. As a result, the vibration transmitted through the ossicles to the inner ear is reduced, decreasing the degree of stimulation of the receptors (hair cells) present in the inner ear. Thus, the reflex checks overstimulation of hair cells and prevents the damage to the cochlea. Transmission of sound waves to the inner ear through the tympanic membrane and the ossicular chain. Amplification of sound waves: the force of sound waves that strike the tympanic membrane increases several times as it reaches the footplate of stapes and oval window. The surface area of the tympanic membrane (50 mm2) is much larger than that of the oval window (3 mm2), the ratio being 17:1. The total force of a sound wave exerted on the tympanic membrane is transmitted to the oval window. But due to the decrease in the sur face area, the pressure (force per unit area) increases 17 times. The ossicular chain acts as lever while transmitting the vibration of sound waves. In this manner, the middle ear performs the job of impedance matching (Application Box 149. The masking of most of the lowfrequency environmental noise allows the human voices to be audible inspite of noise in the environmemt. They contract before and during any movement that may stimulate the ossicleslike chewing, swallowing, yawning, walking and gross bodily activities and, thereby, suppres the sounds produced by these movements. Contraction of tensor tympani and stapedius related to speech and movements are not reflex responses as they contract prior to these events. So, the conduction of sound from air to fluid meets with considerable acoustic impedance (resistance). If the sound waves were to strike the oval window directly (without traversing through the tympanic membrane and the ossicular chain), only 0. This is known as impedance matching and the middle ear is, therefore, often called an impedance-matching device.

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Syndromes

• Trauma from explosions, fireworks, gunfire, rock concerts, and earphones
• Nasal spray
• Relationship, work, and family problems
• Headache
• Washing of the skin (irrigation) -- perhaps every few hours for several days
• What does the sore look like and where is it located?
• Labetalol (Normodyne)