Jeffrey W. Taub MD

• Professor Department of Pediatrics
• Wayne State University School of Medicine
• Hematologist/Oncologist
• Department of Pediatric Hematology/Oncology Children's
• Hospital of Michigan
• Detroit, Michigan

This produces a focus gradient within the renal medulla which is essential in maintaining water steadiness cholesterol medication for high triglycerides buy 10 mg atorlip-10. Sodium is actively pumped out of the distal tubules cholesterol lowering foods diet quality 10mg atorlip-10, and resorbtion is modified by aldosterone secretion cholesterol levels patient uk cheap 10mg atorlip-10 otc. Sodium is actively pumped out of the amassing tubules in opposition to a concentration gradient to preserve the hypertonicity of the renal medulla cholesterol lowering diet foods to avoid 10 mg atorlip-10, with related passive resorbtion to a small degree cholesterol numbers atorlip-10 10mg online. A number of substances are secreted in the distal tubule cholesterol test alcohol buy atorlip-10 10mg otc, together with potassium and hydrogen and drugs. At this stage 75% of the potassium content material of urine outcomes are as a end result of tubular secretion. Potassium secretion is linked with sodium and hydrogen concentrations and is modified by aldosterone secretion. Any increase in medullary blood circulate leads to dissipation of medullary osmolality, decreased water resorbtion and the production of enormous quantities of dilute urine. There are additionally volume receptors in the atria and nice veins which seem to be beneath the management of the vagus nerve. Maintenance of acid-base balance relies upon a posh series of buffer mechanisms. The renin-angiotensin system is necessary, with renin being released from juxtaglomerular cells in response to sympathetic nerve stimulation through a lower in afferent arteriolar pressure and hyponatraemia. These effects feed back in a unfavorable trend and swap off renin secretion and, due to this fact, preserve homeostasis. Sodium and chloride are transported out of the ascending limb of the loop of Henle, and the sodium concentration falls progressively as the distal tubule is reached. The remainder of the loop of Henle is in osmotic equilibrium with the substance of the kidney. As the iso-osmolar filtrate reaches the bottom of the loop of Henle the contents of the descending limb turn out to be extra concentrated as a end result of being pushed towards the ascending limb. Other essential hormones that are the subject of contemporary research embrace kallikrein (produced in the distal nephron) and other related agents. These substances are important vasodilators and still have been proven to have motor results inside the lower urinary tract and may be involved in sensorimotor mechanisms throughout the bladder. The kidney is also involved in calcium metabolism and produces 1 -hydroxylase in response to low circulating levels of calcium, which acts to convert 25-hydroxycholecalciferol in to the active metabolite 1,25-dihydroxycholecalciferol, which then promotes calcium reabsorbtion and reduces urine excretion to maintain homeostasis. Erythropoietin is produced by the kidney in response to hypoxia (either because of anaemia or respiratory causes), excessive circulating ranges of the merchandise of purple cell destruction, and vasoconstriction. Erythropoietin stimulates an increase in the variety of nucleated red cells within the haemopoietic tissue, thereby elevating pink cell and reticulocyte counts in peripheral blood. Indeed synthesised erythropoietin is utilized in modern haematological follow, for these very functions, especially in intractable anaemia related to continual renal failure. The renal cortex and medulla synthesise a number of prostaglandins whose precise perform remains obscure at current. Uric acid stones can result from the use of high dose aspirin, thiazide diuretics and furosemide. Increased symptoms can result from the effect of agents rising urine production. Acute renal failure that is an abrupt decline in renal operate with a lack of regular exercise. A daily urine output of less than 500 mL is termed oliguria; the absence of urine formation is anuria. The underlying cause of acute renal failure is a persistent fall in renal blood flow to ranges 30�40% of normal with a consequent discount in glomerular filtration to less than 5 mL/min. The causes of acute renal failure could be divided broadly in to prerenal, renal and postrenal. Prerenal acute renal failure often outcomes from dehydration or circulatory collapse producing hypovolaemia associated with situations similar to blood loss, septicaemia, or trauma. Renal causes may be broadly considered to be interstitial (drugs or infection), glomerular (autoimmune conditions, diabetes), tubular damage (antibiotics, drugs, toxic chemicals), or renal (vasculitis or thrombosis). Routine biochemical investigations which are helpful in analysis of acute renal failure are summarised in Table 18. An ultrasound scan is a particularly useful diagnostic investigation and is often mixed with a plain Table 18. Nephrotoxic medication embrace heavy metals, natural solvents, radiological contrast media (the combination of radiological contrast plus metformin has just lately been recognised as being toxic), antibiotics corresponding to aminoglycosides and some cephalosporins, chelating agents, paraquat and penicillamine. Ureteric obstruction can happen both as a direct result of drug motion (predominantly of historic interest now). The main goal of the remedy of patients with acute renal failure is to determine a cause and institute acceptable treatment. Sodium consumption is restricted to 20�30 mmol per day, and cautious monitoring of metabolic and nutritional status is necessary. H2 receptor antagonists and antacids are often used because of the related incidence of higher gastrointestinal haemorrhage. Indications for haemodialysis embody: � � � hyperkalaemia; metabolic acidosis; and fluid overload with pulmonary oedema. The medical course of acute renal failure is very variable relying upon the aetiology and could be thought-about to comprise oliguric, diuretic and postdiuretic phases. The oliguric phase usually starts early on however may be extended for as much as three months or extra. It is necessary to keep vigilance notably during this time due to the potential for loss of fluid and electrolytes. Renal operate might proceed to enhance for up to a year, however distal tubular perform is usually permanently impaired, although this might be tough to determine clinically. Acute renal failure is a situation with a high mortality, with the worst prognosis being related to haemorrhage, trauma, peritonitis, advanced age and an infection. Often no aetiological issue can be discovered as a trigger for chronic renal failure, and you will want to attempt to differentiate the condition from acute renal failure, to determine its aetiology and the severity of the illness course of. The commonest causes of chronic renal failure embrace diabetes mellitus, glomerulonephritis, persistent pyelonephritis, hypertension, connective tissue ailments, and polycystic kidneys. Other causes embody renal calculi, vesicoureteric reflux, bladder outlet obstruction and myeloma and hypercalcaemia. Patients with chronic renal failure usually have polyuria with loss of normal concentrating capability. Nocturia is commonly said to be an early signal and the urine incorporates protein with granular casts and white blood cells. Sodium is progressively retained in persistent renal failure, albeit the serum sodium degree is a poor reflection of this. In finish stage persistent renal failure potassium ranges might rise and acidosis is inevitable due to decreased ammonium ion excretion and decreased excretion of buffer phosphate, the urine pH usually being lower than 5. Anaemia happens as a consequence of persistent renal failure, which is often normochromic and normocytic and is likely to be because of marrow suppression with lowered purple cell survival. Appropriate investigation of sufferers with chronic renal failure along with biochemical investigations includes ultrasound scan of the upper tracts and a check on postvoiding residual urine. It should be remembered that up to a third of sufferers with persistent retention of urine current with persistent renal failure. The goal of conservative therapy is to delay the progressive deterioration of renal function and its consequences. Fluid intake should be controlled to produce a urine output of roughly 1 L/24 h, blood strain is controlled by the use of antihypertensive medicine, and cardiac failure is handled utilizing normal measures. In some patients protein intake is restricted to 40 g/24 h to have the ability to reduce the production of nitrogenous waste products. When conservative measures fail, dialysis is instituted, and that is usually in patients in whom the serum creatinine has risen above 1000 mmol/L or if the creatinine clearance is less than 1 mL/min. In temporary, the precept of haemodialysis is to enable selective diffusion of molecules below a sure measurement from the peripheral blood in to the dialysis fluid. Wherever attainable, renal transplantation is carried out, however that is limited by the availability of transplant organs, the suitability of these organs based on tissue typing, and the supply of appropriate resources. After cleaning the external urethral meatus the first 20 mL or so of urine is discarded before amassing the following part of the voided urine in a sterile container. Nevertheless stick exams are very useful and supply easy access to urine testing in a screening situation. The quantity of protein in the urine is often less than one hundred mg/24 h, and glycosuria should all the time increase the suspicion of diabetes mellitus, which should be investigated additional with a fasting blood glucose. Microscopy of the urine permits the presence of red cells, white cells and casts to be demonstrated. Early morning urines are classically collected to test for acid fast bacilli; normally three specimens are collected on separate events and cultured. Terminal stream urine specimens are characteristically recommended for examination of the urine for parasites and ova. Blood checks Renal function is routinely assessed by measurement of the plasma urea and creatinine, nevertheless it have to be remembered that important renal dysfunction can occur (loss of two-thirds of the renal reserve) before the urea and creatinine rise. The most correct guide to renal function is creatinine clearance, normally 100� a hundred and forty mL/min, which approximates to the glomerular filtration rates. A spot check of urine is distributed for cystine evaluation, and 24 h assortment of urinary excretion of calcium and uric acid are estimated. Diagnostic imaging A plain belly x-ray is helpful to detect delicate tissue lots of the renal areas or pelvis, and approximately 60% of urinary tract calculi are sufficiently radioopaque to be seen on plain x-rays. Ultrasound scanning is used for diagnosing the presence of cystic and strong lesions of the kidney, and in addition for assessing residual urine volumes retained throughout the bladder after micturition. Ultrasound can be helpful for the demonstration of lesions within the scrotum, and is the investigation of choice in instances of suspected testicular malignancy. It can be used for pre-operative planning in management of both malignant and calculous disease. Arteriography now is uncommonly used but is especially helpful in the context of renal vascular issues when associated with renal trauma. Venography is used in the context of therapeutic manoeuvres corresponding to embolisation of varicoceles. Interventional radiology via the location of nephrostomy tubes has revolutionised our management of urinary tract calculous illness and obstruction of the upper tracts. Such methods permit the percutaneous placement of a nephrostomy tube which decompresses the obstructed higher tract and allows the antegrade visualisation of the higher tract by way of distinction media and can be used therapeutically for the position of a stent in an antegrade trend, which can be particularly helpful within the context of malignancy or external fibrotic processes inflicting obstruction to the ureter. The use of an externally positioned counter permits important information on renal tract function and obstruction to be obtained. This is carried out both as a static or dynamic process, in accordance with the data desired. The initial uptake supplies an evaluation of blood circulate to the kidney, the so-called vascular part. The price rises and slows as isotope is concentrated and handed in to the collecting system of the kidney (the filtration phase). A peak is then reached as isotope passes down the ureter in regular state with the quantity arriving by way of the accumulating system. As the amount arriving by way of the collecting system then drops off, the activity falls as isotope is transported down the ureter (excretion phase). Administration of this compound is usually combined with that of a diuretic corresponding to frusemide and allows some remark to be passed on the presence or absence of obstruction to the upper tract. Technetium-labelled compounds are commonly used for bone scanning to verify for metastases in association with prostatic carcinoma. Lower urinary tract perform Urodynamic assessment of the urinary tract relates to the research of stress and move relationships inside the urinary tract. Urodynamic tests must be thought-about to characterize a hierarchy of investigations: Radionuclide studies Renography is an important aspect of the investigation of the higher urinary tract. The simplest urodynamic approach is to assess the volume of fluid the patient takes in and the volume they cross out. By measuring the amount voided, one can assess the practical capability of the bladder, and as nicely as the affected person can record the variety of incontinent episodes that they experience if incontinence is an issue. However, if the residual is a hundred and fifty mL or extra then more and more one suspects poor detrusor operate. The most accurate way of defining lower urinary tract function is to measure the pressure inside the bladder and synchronously the strain within the rectum. A number of pc packages exist to enable this calculation to be made simultaneously during any urodynamic examine. Any rise in pressure while the patient is conscious and cooperative results in the definition of detrusor overactivity. Any impairment of bladder filling within the absence of a strain rise results in the analysis of a hypersensitive bladder (provided that other pathology similar to infective and neoplastic disorders has been excluded), and is called a sensory disorder. The affected person then voids, in women with a strain of 30�40 cmH2O and in men of 40� 50 cmH2O with a move fee of as much as 30�40 mL/s in ladies and up to 25�30 mL/s in males. Combining a cystometrogram with the utilization of contrast media as a filling solution leads to the so-called videocystometrogram, which represents the gold normal investigation, as anatomical element referring to the decrease urinary tract could be seen in addition to the presence of reflux in the path of the higher tracts. Cystourethrography, and particularly videocystometry, are particularly helpful in the investigation of patients with a storage drawback presenting with frequency and incontinence. Cystourethrography, by permitting anatomical definition of the decrease urinary tract, allows evaluation of the degree of prolapse of the bladder base and in addition can enable the confirmation of stress urinary leakage on asking the affected person to cough. Other investigative strategies relating to the lower urinary tract, together with electromyography and urethral pressure profile, are analysis tools and not in widespread scientific use. The parasympathetic acts in synergy with the sympathetic nervous system, which opposes its action and, subsequently, acts to retailer urine. Disease states affecting the decrease urinary tract could be thought-about as: � � failure to retailer; and failure to empty.

Before reaching the ground of the mouth the lingual nerve lies towards the periosteum of the alveolar course of closely associated to the third molar tooth cholesterol profile definition order atorlip-10 10 mg fast delivery. The hypoglossal nerve descends between the inner jugular vein and the interior carotid artery cholesterol levels in fertilized eggs generic atorlip-10 10mg overnight delivery, giving branches to thyrohyoid and geniohyoid muscles cholesterol test at walgreens generic atorlip-10 10 mg on line. It supplies the superior limb of the ansa cervicalis (C1) to innervate the infrahyoid muscles cholesterol levels medication order atorlip-10 10 mg free shipping. Classical descriptions attribute three surfaces to the gland: � � � lateral or superficial surface; anteromedial or anterior surface; and posteromedial or deep surface cholesterol test buy purchase atorlip-10 10mg on line. Superficial surface Tongue There is pure airplane of separation between the skin and the superficial surface cholesterol check guidelines purchase online atorlip-10. Anteromedial surface This, actually, is U-shaped extending from the lateral floor of the masseter to the medial floor of the medial pterygoid muscle winding around the posterior border of the mandibular ramus. Where this floor meets the superficial floor is the convex anterior border from which emerges the parotid duct and the 5 branches of the facial nerve. The stylomandibular ligament separates the deep aspect of this surface from the submandibular gland. Sternocleidomastoid Submandibular gland Submandibular duct Sublingual gland Sublingual ducts. Posteromedial floor region and solidified round numerous important constructions. The story emphasises the complex configuration and relations of the gland which can little question be appreciated by a surgeon doing a total parotidectomy. The parotid gland lies between the mastoid process and the sternocleidomastoid posteriorly, and the ramus of the mandible, which it clasps anteriorly. The parotid gland is enclosed in a tricky capsule derived from the investing layer of the deep fascia. Inflammation of this gland produces ache as the gland swells inside the unyielding capsule. It lies between the muscle and mucous membrane for a short distance before piercing it and the valvular flap thus produced prevents inflation of the gland when the intra-oral pressure is raised. It lies along the posteromedial floor (also known as the deep surface) may be very irregular and extra complicated. The gland extends deep to the posterior stomach of the digastric to be related to the styloid process and the stylohyoid muscle. The latter two separate the gland from the carotid sheath and its contents (internal carotid artery, inner jugular vein, and the final 4 cranial nerves). Structures passing by way of the parotid gland the external carotid artery, the retromandibular vein and the facial nerve pass through the parotid gland. The exterior carotid artery enters the posteromedial floor inferiorly and divides inside the gland in to its terminal branches, the maxillary and the superficial temporal arteries. The retromandibular vein, which emerges from the posteromedial floor, is shaped inside the gland by the union of the maxillary and the superficial temporal veins which enter the gland on its anteromedial floor. During parotidectomy, the trunk of the nerve is approached along a aircraft in entrance of the anterior margin of the cartilage. The stylomastoid branch of the posterior auricular artery is superficial to the nerve and can be a information to its proximity. Before getting into the gland the next three branches are given off from the nerve: � � � � zygomatic for the orbicularis oculi; buccal supplying the buccinator and the higher lip muscle tissue; marginal mandibular supplying the lower lip muscular tissues; and cervical for the provision of platysma. The facial nerve enters the posteromedial surface of the parotid gland about 1 cm after rising from the skull. It then passes forward within the gland as probably the most superficial of the three embedded constructions. These two further divide to kind the 5 terminal branches: There is appreciable variation in the sample of the branching inside the gland. Parotidectomy requires precise identification and dissection of the facial nerve and hence a exact information of anatomy of the gland is important to keep away from harm to the nerve. Differentiating an enlargement of the gland from that of the lymph nodes may be difficult. The superficial floor of the gland is roofed by the pores and skin, platysma and the investing layer of deep fascia and is crossed by the facial vein, the cervical branch of the facial nerve and likewise usually by the marginal mandibular department of the facial nerve. The marginal mandibular branch lies deep to the platysma and is considered one of the most necessary relations of the gland. This branch which supplies the depressor anguli oris and the depressor labii inferioris is liable to injury during surgery of the submandibular region. Skin incisions within the submandibular region are made about 4 cms under the mandible to keep away from damage to the marginal mandibular department. The two elements, nonetheless, are continuous with one another posteriorly and the concavity thus fashioned is occupied by the free posterior border of the mylohyoid muscle. The facial artery grooves the deep surface and emerges on to the face by passing between the gland and the mandible. The deep part this lies within the flooring of the mouth, superior (deep) to the mylohyoid and is covered by the mucosa of the oral cavity. Medially it lies on the hyoglossus and is said to the lingual nerve, the submandibular ganglion and the hypoglossal nerve. Here it turns ahead and medially and emerges on to the floor of the hyoglossus muscle. It runs ahead deep to the mucosa of the ground of the mouth between the mucosa and the sublingual gland and the geniohyoid muscle to open in to the ground of the mouth on either side of the frenulum of the tongue. As it goes forward it crosses medial to the nerve to lie above the nerve and then crosses again, this time lateral to it to reach a position once again beneath the nerve. Four nerves are intently associated to the submandibular glands and therefore are vulnerable during its removing. The proper half of the mandible and part of the submandibular and sublingual glands have been eliminated. The glossopharyngeal nerve, stylohyoid ligament and lingual artery pass deep to the posterior border of hyoglossus; the lingual nerve, submandibular duct and hypoglossal nerve are superficial to hyoglossus. Sublingual gland the sublingual gland lies in the floor of the mouth and raises the sublingual fold of the oral mucosa. The gland is medially related to the genioglossus muscle and laterally to the sublingual fossa of the mandible. The parasympathetic provide of the submandibular and sublingual glands is from the facial nerve via its chorda tympani department. The chorda tympani joins the lingual nerve and the preganglionic fibres synapse in the submandibular ganglion. The postganglionic fibres rejoin the lingual nerve to be distributed to the glands. It has three components: � � � Nerve supply of the salivary glands the secretomotor supply to the parotid gland is from the glossopharyngeal nerve, the parasympathetic fibres nasopharynx opening anteriorly to the nasal cavities; oropharynx opening to the oral cavity; and laryngopharynx or hypopharynx opening in to the larynx and persevering with downwards as the oesophagus. The cartilaginous end of the tube has a prominence at the postero-superior part of the opening. The roof and the posterior wall has lymphoid accumulation within the mucosa forming the adenoids. Examination of the nasopharynx could be done by inserting a small angled mirror within the oropharynx. The following can be visualised: � � � � � � opening of the Eustachian tube; the tubal elevation; the pharyngeal recess; nasopharyngeal tonsils or adenoids � seen as vertical ridges separated by clefts; the posterior choanae; and the posterior finish of inferior concha or turbinate. There are extra branches from the lingual, ascending palatine and ascending pharyngeal arteries as properly. The troublesome paratonsillar vein which frequently bleeds throughout tonsillectomy extends from the taste bud to lie on the lateral floor of the tonsil before piercing the superior constrictor. The lymphatic drainage is to the jugulo-digastric lymph node located behind the angle of the mandible. The sensory nerve provide of the tonsillar fossa is through the glossapharyngeal nerve with minor contribution from the lesser palatine nerve. Laryngopharynx this a half of the pharynx which is also called the hypopharynx has the inlet of the larynx and the piriform fossa. The inlet of the larynx which is vertical is bounded by the epiglottis, aryepiglottic fold and the arytenoids. It is a standard site for lodging international our bodies corresponding to fish bones and in addition infamous for malignant tumours which can be silent within the early phases. The inner laryngeal nerve which supplies the laryngopharynx and most of the larynx can be found in the piriform fossa. As this part has a rich lymphatic drainage the tumour quickly spreads in to the deep cervical nodes. The nasopharyngeal tonsils are outstanding in youngsters however like all lymphoid tissues undergo atrophy after puberty. Infection from the nasopharynx can easily unfold in to the middle ear via the Eustachian tube. Oropharynx and the anatomy of the tonsil an important construction within the oropharynx is the palatine tonsil or the tonsil. It lies in the tonsillar fossa bounded by the anterior and posterior pillars of the fauces. The anterior pillar is the palatoglossal arch produced by the palatoglossus muscle and the posterior pillar is the palatopharyngeal arch by the palatopharyngeus muscle. Pharyngobasilar fascia lining the inside floor of the constrictor varieties the capsule of the tonsil and lies between the tonsil and the muscle. Its oral surface is lined by mucous membrane having stratified squamous epithelium. Structure of the pharynx the pharyngeal wall consists of the: � � � � � the mucosa; submucosa; pharyngobasilar fascia; muscle; and buccopharyngeal fascia (areolar tissue). Blood supply the principle arterial supply is derived from the tonsillar department of the facial artery which pierces the superior the mucosa has pseudostratified columnar ciliated epithelium (respiratory epithelium) in the nasopharynx and stratified squamous epithelium in the relaxation of the pharynx. The pharyngobasilar fascia lies deep to the mucosa and lines the muscular tissues of the pharynx. It is thick within the higher half and its attachment to the bottom of the cranium provides firm anchorage to the pharynx. These are strengthened by a lot smaller longitudinal muscle tissue: � � � stylopharyngeus; salpingopharyngeus; and palatopharyngeus. Cartilages There are 5 main cartilages: Each constrictor muscle begins from a limited origin anteriorly and broadens out laterally and posteriorly to insert in to a posterior midline raphe � the pharyngeal raphe. The hole between the inferior and middle are occupied by the thyrohyoid ligament and related buildings. The stylopharyngeus muscle accompanied by the glossopharyngeal nerve enters the pharynx by way of the hole between the middle and superior constrictors. The gap between the higher border of the superior constrictor and the base of the skull is bridged by the thick pharyngobasilar fascia. Anteriorly the superior constrictor is attached to the pterygomandibular raphe and the center constrictor to the larger horn of the hyoid bone. The thyropharyngeus part of the inferior constrictor is fan-shaped like the opposite constrictors and is attached to the lamina of the thyroid cartilage. The cricopharyngeus part of the inferior constrictor is circular and acts like a sphincter. The weakest area of the pharyngeal wall is the hole between the thyropharyngeus and the cricopharyngeus posteriorly in the midline. Cricoid cartilage Shaped like a signet ring, the cricoid cartilage has a slender arch anteriorly and a broad lamina at the back. Thyroid cartilage the thyroid cartilage is the most important of the laryngeal cartilages and has two laminae assembly within the midline anteriorly. This cartilage articulates inferiorly with the cricoid on the cricothyroid joints and is related to the hyoid bone by the thyrohyoid ligament. Epiglottis this is a leaf-shaped cartilage forming the anterior wall of the inlet of the larynx. Its slender lower finish is connected to the thyroid cartilage by the thyroepiglottic ligament. The thyroepiglottic ligament tethers its anterior floor to the again of the hyoid bone within the midline. Arytenoid cartilages these are paired cartilages which are pyramidal in form articulating with the lamina of the cricoid. In its broader lower part the arytenoid has the vocal process projecting anteriorly and the muscular process laterally. The former receives attachment of the vocal ligament and the latter the abductors and adductors of the vocal cord. Though small, these are important for full approximation of the inlet of the larynx. Innervation of the pharynx Motor innervation All the muscle tissue of the pharynx besides stylopharyngeus are supplied by the pharyngeal branch of the vagus, fibres coming from the nucleus ambiguus by way of the cranial part of the accessory nerve. These are: Epiglottis Hyoid bone Aryepiglottic fold Vestibule of larynx Quadrangular membrane Thyroid cartilage Saccule Vestibular fold Sinus of larynx Rima glottidis Vocal ligament Conus elasticus � � Quadrangular membrane � this types the higher part of the wall. Its upper free border types the aryepiglottic fold and the lower free border varieties the core of the vestibular fold or the false vocal wire. It is hooked up below to the arch of the cricoid, above to the vocal process of the arytenoid posteriorly and the thyroid cartilage in the midline anteriorly. Between its thyroid and arytenoid attachment it has a free border, the vocal ligament, forming the core of the vocal fold or vocal twine. The part between the cricoid and the thyroid cartilage in the midline anteriorly is thickened to type the cricothyroid ligament. This is definitely palpable, is comparatively avascular, and is the site for laryngotomy (cricothyroid stab) in acute laryngeal obstruction. Mucous membrane the mucosa in the supraglottic area is loosely bound to the underlying wall. In laryngeal oedema fluid accumulates in the submucous house and the mucosa swells up and obstructs the airway. The lack of a submucousal layer additionally makes the vocal cords comparatively less vascular and hence it seems paler than the the rest of the mucosa.

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Studies have shown cholesterol nucleation definition buy atorlip-10 10mg, on the idea of allergicspecific IgE definition of cholesterol in food order atorlip-10 with amex, that imported fireplace ants will be the arthropod posing the best threat for anaphylaxis to adults who reside in endemic areas cholesterol levels lowering foods buy atorlip-10 on line. Systemic reactions typically occur in patients beforehand sensitized to hearth ant stings cholesterol levels nice generic atorlip-10 10 mg free shipping, but as a outcome of their venom incorporates allergenic proteins which might be antigenically similar to cholesterol test alcohol before generic atorlip-10 10mg free shipping other hymenopteran venom cholesterol levels chart in south africa buy generic atorlip-10 10mg on-line, preliminary sensitization may occur with a bee or wasp sting. Conventional and rush immunotherapy performed with imported fire ant whole-body extract has proved effective and protected for the therapy of this type of hypersensitivity. The fire ant will get its name from the fierce burning discomfort caused by its sting, not from its color, which ranges from dark pink to brown or black. Most stings happen through the late spring and early summer time, when the ants are most active and their venom is most potent. Secondary an infection could also be the purpose for the go to, after painful pustules, cellulitis, or lymphangitis develops. Have the patient wash the realm and repeat the dressings till full therapeutic has taken place. When cellulitis or lymphangitis is current, present acceptable antibiotics (see Chapter 166). Cleanse the area with povidone-iodine; then, using a 25-gauge needle, aspirate the blister fluid until the blister has completely collapsed. To prevent contamination and an infection, both present continuous antibacterial ointment (bacitracin) and strip bandage protection, or cover the punctured blister with a polyurethane movie (such as OpSite) or a hydrogel dressing (such as Spenco 2nd Skin or Vigilon), or seal the needle puncture with cyanoacrylate (Dermabond). A correctly becoming shoe is crucial, and even comfortable shoes have to be damaged in steadily. Good socks with moisture wicking and padded insoles also can help prevent friction blisters. Wearing two pairs of socks which would possibly be made of different supplies could scale back pores and skin friction and forestall blisters. United States Military Academy cadets who applied an antiperspirant resolution containing 20% aluminum chloride to their feet for no less than three consecutive days lowered their threat for developing foot blisters throughout a 21-km hike by approximately half. The use of such antiperspirants sadly causes a excessive incidence of pores and skin irritation. This will result in unnecessary discomfort from the denuded area in addition to enhance the chance for an infection. Discussion Blisters result from frictional forces-compounded by perspiration-that mechanically separate epidermal cells at the degree of the stratum spinosum. Although such blisters not often cause significant medical problems, they can be fairly painful and hinder athletic efficiency. Treatment targets embrace sustaining comfort, promoting therapeutic, and stopping infection. These prominent, uncovered surfaces turn out to be blanched and develop paresthesias and numbness however remain pliable. Superficial frostbite could be either a partial- or a full-thickness freezing of the dermis. The frozen surfaces seem white or mottled, feel doughy or exhausting, and are insensitive. The capability to sense mild contact and noxious stimuli helps decide the prognosis. Dark colour, hemorrhagic blisters, cyanosis, and exhausting nondeforming skin recommend deep harm. A robust parenteral analgesic, similar to morphine or hydromorphone (Dilaudid), may be required to control pain. Mild hypothermia may be handled with passive exterior rewarming, which consists of placing the affected person in a heat dry setting after removal of moist clothing. Adding heating blankets or a pressured heated air system (active external rewarming) will improve the rate of restoration. If the blisters are open, nevertheless, they should be d�brided and gently cleansed with 1% povidone-iodine and normal saline. Although topical aloe vera is now usually really helpful, it has not been proven to enhance tissue viability. Injured tissue ought to be dealt with gently, and dressings should be unfastened, noncompressive, and nonadherent. More intensive involvement (often something more than first-degree injury) requires hospitalization. Hands and toes ought to be splinted and elevated to scale back edema, and the digits have to be separated by nonadherent gauze. Intravenous hydration with crystalloid will theoretically cut back blood viscosity and capillary sludging. Outpatients must be provided with follow-up care and warned that healing of the deeper injuries may be slow and produce pores and skin that is still sensitive for weeks. Late sequelae of superficial frostbite embrace cold hypersensitivity (53%), numbness (40%), decreased sensation (33%), and impaired capability to work (13%). Reexposing even mildly frostbitten tissue to the cold without complete rewarming may find yourself in additional injury. Smoking causes vasoconstriction and should additional decrease blood circulate to the frostbitten extremity. Severe frostbite, when the deep tissue or extremity is frozen with a woody feeling and lifeless look, requires inpatient administration and could possibly be associated with life-threatening hypothermia. Discussion Current scientific information suggests that localized chilly injury represents a steady spectrum ranging from minimal to extreme tissue destruction and loss. First-degree frostbite is characterized by an anesthetic central white plaque with peripheral erythema. Second-degree harm reveals blisters crammed with clear or milky fluid surrounded by erythema and edema, which seem in the first 24 hours. Third-degree damage is related to hemorrhagic blisters that result in a hard black eschar, seen over the course of 2 weeks. In general, treatment for the 4 classes of frostbite is identical until demarcation occurs within three to 4 weeks after damage. Hypothermia is assessed as being either delicate (as beforehand described) or moderate-with temperatures between 28� C and 32� C, lack of shivering, and diminished degree of consciousness- or extreme, with core temperatures under 28� C and loss of reflexes, coma, and, ultimately, ventricular fibrillation and death. Moderate to severe hypothermia is a medical emergency necessitating maintenance of airway, breathing, and circulation. Most victims of hypothermia and localized cold injuries are in one of three classes: the city poor, wilderness fanatics, and winter sports activities individuals. The areas of the body most probably to undergo are these farthest from the trunk or massive muscles: ear lobes, nose, cheeks, fingers, arms, toes, and toes. Touching chilly metal with bare arms could cause immediate frostbite, as can the spilling of gasoline or other risky liquids on the pores and skin when the temperature is very low. Factors contributing to hypothermia in addition to localized chilly accidents embrace alcohol intoxication, homelessness, and major psychiatric problems. For those that participate in winter out of doors recreational and sports activities activities, direct exposure of skin and carrying constricting clothes, similar to tight-fitting footwear, will predispose them to frostbite. Frostnip is a superficial freezing of the pores and skin, a precursor to frostbite, and produces reversible skin modifications, together with blanching and numbness that resolve with warming. With mild rewarming, the frostnip-affected space turns into hyperemic, and the feeling of pain returns quickly. Frostbite happens when tissue freezes and crystals kind within the extracellular space between cells. With dehydration, vasoconstriction, and low epidermal temperature, circulation is restricted as blood viscosity increases, and water, hydrostatically pulled out of cells, begins to freeze. Close to 60% of frostbite accidents involve the lower extremities, specifically the great toe and toes. Predisposing ailments can include Raynaud illness, peripheral vascular disease, and diabetes mellitus. Tobacco smoking is one other factor that can enhance the chance of growing frostbite. Individuals in cold and isolated areas ought to never be alone, or they want to carry communication devices, such as cell telephones or walkie-talkies. The first layer must be manufactured from polypropylene and the second layer manufactured from wool. During this prodromal stage, which might last several days, there may be accompanying preherpetic neuralgia. Patients complain of signs that range from an itch or tingling to extreme lancinating ache, tenderness, dysesthesias, paresthesia, or hypersensitivity that covers a specific dermatome. The discomfort may be troublesome for the affected person to describe, usually alternating between an itch, a burning, and even a deep aching ache. Prior to the onset of the rash, zoster may be confused with pleuritic or cardiac pain, cholecystitis, or ureteral colic. The ache might precede the eruption by as a lot as a few weeks, and occasionally, ache alone is the one manifestation (zoster sine herpete). Although virtually solely a unilateral disease, in a single study, approximately 1% of sufferers had bilateral involvement. The early rash consists of an eruption of erythematous macules and papules that usually appear posteriorly first after which unfold anteriorly alongside the course of an concerned nerve phase. These continue to kind for three to 5 days and then evolve by way of states of pustulation, ulceration, and crusting. The skin eruption often is limited to a single dermatome; the most generally concerned dermatomes are the thoracolumbar region and the face. Lesions could contain more than one dermatome and occasionally may cross the midline. With seventh cranial nerve involvement (causing weak point of all facial muscle tissue on one side), the rash shall be found in the ipsilateral external ear (called zoster oticus), or vesicles may be seen on the exhausting palate. What To Do: If it has been 3 days or less for the rationale that onset of the rash, prescribe valacyclovir (Valtrex), a thousand mg tid � 7 days; famciclovir (Famvir), 500 mg tid � 7 days; or the a lot less expensive however more inconvenient acyclovir (Zovirax), 800 mg five times per day � 7 days. If a affected person presents later than 72 hours after onset, antivirals should still be considered if new lesions are being fashioned. Prescribe analgesics acceptable for the extent of pain the patient is experiencing. If the ache is extreme, think about referring the patient for an epidural nerve block, which has been successful in relieving the acute pain and should lower the incidence of postherpetic neuralgia. There is proof that treating older sufferers (60 years of age and older) with amitriptyline (Elavil), 25 mg qd � ninety days, will cut back the chance for postherpetic neuralgia. Dressing the lesions with gauze and splinting them with an elastic wrap can also assist convey aid. Superficial an infection could additionally be prevented by means of a topical antibiotic ointment, such as mupirocin (Bactroban) 2% ointment (1 tube, 22 g), applied bid. Secondary an infection should be handled with systemic antibiotics, corresponding to cephalexin, 500 mg qid � 7 to 10 days, or azithromycin, 500 mg, then 250 mg qd � four days. Look for punctate keratopathy on slit-lamp examination with fluorescein staining, though patients might have solely ache, lacrimation, conjunctivitis, or scleritis. Herpes zoster ophthalmicus may end up in corneal scarring, uveitis, glaucoma, corneal perforation, or blindness. Do not provoke a complete diagnostic workup to look for an occult malignancy merely on the premise of zoster. Patients with cancers, significantly lymphomas, are, however, at increased danger for zoster. Discussion Herpes zoster can normally be readily identified from its scientific appearance of typical lesions in a dermatomal distribution. The virus invades the facial nerve, particularly the geniculate ganglion, and sometimes the auditory nerve, and may produce the peripheral seventh-nerve palsy, along with hearing loss, vertigo, and taste dysfunction. Antiviral remedy has been shown to shorten the length of viral shedding, halt the formation of new lesions more rapidly, accelerate the speed of healing, and cut back the severity of acute ache. Herpes zoster ophthalmicus is a particularly essential variant, and these sufferers should definitely obtain antiviral therapy early with the goal of preventing ocular complications. Antiviral remedy is usually beneficial for all patients of any age with severely symptomatic herpes zoster and for patients older than age 50 years with zoster of any severity. It results from reactivation of latent herpes varicella-zoster (chickenpox) virus residing in dorsal root or cranial nerve ganglion cells. In immunocompetent patients, zoster is often a self-limiting localized illness and heals inside three to four weeks. Most patients can be reassured that their disease will abate with out permanent issues. The incidence in immunocompromised sufferers is as much as 10 instances higher than in immunocompetent hosts, and often their therapy should be more aggressive. In these immunocompromised sufferers, herpes zoster can turn into disseminated, with lesions appearing exterior the first dermatomes and with visceral involvement. This is extra likely to happen in older sufferers (60 years of age or older), those in whom the diploma of skin surface concerned is larger, and people with severe pain at time of presentation. Pain can persist for months and in some patients for many years and can be the supply of debilitating neuropathic ache, with considerable physical and psychosocial morbidity. The tricyclic antidepressant amitriptyline (Elavil) can be utilized to treat such pain. The most common unwanted aspect effects are dry mouth, constipation, and sedation, which are generally not a significant drawback on the relatively low doses wanted for effect (average dosage being 70 mg daily). At current, probably the most promising analgesic approaches for reducing the risk for postherpetic neuralgia, beyond that achieved by antiviral brokers, is treatment with an opioid analgesic or with one of many anticonvulsant medication, corresponding to gabapentin (Neurontin) and pregabalin (Lyrica). The dosage may be started at 300 mg every day divided tid and titrated over 2 weeks to a most of 1800 mg every day divided tid (although dosages up to 3600 mg have been used).

Skin breakdown can be a vital drawback cholesterol of 200 order atorlip-10 with a mastercard, and sufferers ought to be instructed to take away the splint day by day while holding the joint in extension egg cholesterol chart order atorlip-10 10 mg, resting the joint on a flat surface to allow the pores and skin to dry and scale back the possibility of maceration cholesterol ratio ldl cheap atorlip-10 10mg amex. Surgery is beneficial for displaced avulsion fractures with a large articular element (more than 50% of the articular surface) quest diagnostics cholesterol test cost order atorlip-10 with visa, volar subluxation of the distal phalanx lowering your cholesterol foods cheap atorlip-10 10 mg overnight delivery, or failure of splinting cholesterol test in hindi discount atorlip-10 online master card. The clue to this damage is persistent drooping of the distal phalanx and tenderness over the bony insertion of the extensor tendon. Discussion Mallet finger, also called "baseball finger" or "drop finger," entails disruption of the extensor tendon or an avulsion fracture of the distal phalanx. Although this injury is commonly triggered during participation in athletic activities. Given the mechanism, it makes sense that the middle finger, the longest one, is mostly concerned, although a mallet finger might involve any of the digits, including the thumb. Patients could wait weeks to months before being seen and will current with a subsequent swan neck deformity. With a continual mallet finger presentation with out vital bone involvement, splinting in extension should still be attempted however should be done for anywhere from 2 to three months. A Cochrane evaluate looking at interventions for treating mallet finger injuries found inadequate proof to set up the effectiveness of different finger splints in determining when surgery is indicated. It is very snug for the patient, has no absorbent surfaces, and could be worn after washing with out having to take away it to prevent pores and skin maceration. Suggested Reading Hong E: Hand accidents in sports activities medication, Prim Care 32:91�103, 2005. If the character of the harm is in any respect unclear, acquire radiographs before making an attempt a reduction. If there was important delay in looking for help or if the patient is suffering considerable discomfort, a digital block over the proximal phalanx or, most effectively, 1% lidocaine injected immediately in to the joint will permit a more snug discount. When this type of dislocation requires discount, grasp the end of the affected finger between your thumb and index finger and apply regular traction along the lengthy axis. A collateral ligament rupture with resultant ulnar or radial joint instability typically accompanies these dislocations. These dislocations could be lowered by making use of the same principles used for the dorsal dislocation but in reverse. With mild flexion, push the proximal finish of the middle phalanx distally with one thumb, whereas applying traction on the distal phalanx held between your other thumb and index finger till lastly pushing and pulling the center phalanx dorsally in to its normal place. Irreducible dislocations may be caused by avulsion and entrapment of the volar plate within the joint, entrapment of the long flexor tendon in the joint, or entrapment of an osteochondral fragment. These and all open dislocations necessitate immediate consultation with an orthopedist or hand surgeon. Test for avulsion of the central extensor tendon slip by having the affected person attempt to prolong the middle phalanx in opposition to resistance (see Chapter 99). Delayed prognosis of volar plate disruption might lead to continual pseudoboutonni�re deformity (see Chapter 99). If any of those associated injuries exist, orthopedic session ought to be sought, and prolonged splinting and rehabilitation may be required. The true lateral view is most helpful in detecting subtle subluxation and small avulsion fractures on the volar surface. When collateral ligament instability is present, buddy tape the affected finger to the finger adjoining to the ruptured ligament. The tape must be eliminated at night or if the pores and skin turns into moist ( to stop pores and skin maceration). Inform the affected person that joint swelling and stiffness with lack of movement might persist for several months after the initial damage. Active range-of-motion exercises performed by squeezing a gentle foam ball can be useful. Discussion Proximal interphalangeal dislocations are often simple and easily reduced. Most are dorsal dislocations, with the middle phalanx dislocating dorsally, and contain disruption of the volar plate. Early recognition of instability-either dorsal, volar, or lateral-offers the best possibility of closed treatment resulting in satisfactory useful healing. The main goals are to enable volar plate, collateral ligament, or central slip healing, and to restore regular joint operate. Suggested Readings Hong E: Hand injuries in sports medication, Prim Care 32:91�103, 2005. There could have been an preliminary dislocation, which was lowered by the affected person or a bystander (see Chapter 109). Pay specific consideration to the collateral ligaments, the volar plate, and the dorsal insertion of the central slip of the extensor tendon on the base of the middle phalanx. If ache precludes active motion testing or passive stressing of the joint ligaments, think about using a 1% lidocaine digital block or, more effectively, direct joint injection. Test for avulsion of the central anterior tendon slip by having the patient attempt to prolong the center phalanx in opposition to resistance (see Chapter 99). If hyperextension is bigger than that of the identical finger on the uninjured hand, a disruption of the volar plate should be thought-about, because delay in making this analysis may lead to persistent pseudoboutonni�re deformity (see Chapter 99). Have the patient take away the tape while sleeping or if the hand turns into wet ( to stop maceration of the skin), and have him dry the pores and skin completely prior to re-taping. Provide follow-up for active range-of-motion workout routines to restore regular joint mobility. When collateral ligament instability is present, splint the affected finger to the finger adjoining to the ruptured ligament. Inform the patient that swelling, stiffness, and discomfort could persist for several months, and supply follow-up for continued care or bodily therapy. What Not To Do: Do not miss joint instability or tendon avulsion-these accidents require particular splinting and orthopedic referral. Boutonni�re deformity (see Chapter 99) could be prevented by enough examination and diagnosis of volar-plate disruption and central-slip injuries. Early recognition of instability-either dorsal, volar, or lateral-as well as discovering weakness to extension in opposition to resistance, presents the most effective possibility of closed treatment resulting in satisfactory practical therapeutic. The main goals are to allow volar-plate, collateral-ligament, or central-slip healing, and to restore regular joint operate. There could or is in all probability not a subungual hematoma, open nail bed harm, or fingerpad laceration. If there are open wounds, perform a digital block (see Appendix B), thoroughly cleanse and d�bride any open wounds, and repair any nail bed lacerations (see Chapter 146). Early aggressive local wound care has been found to be the most effective prevention in opposition to infection in open fingertip fractures. If necessary, present oral analgesics and advise the affected person to elevate the harm above the heart to reduce swelling. Do not prescribe prophylactic antibiotics for clean and uncomplicated open fractures of the distal tuft. Prophylactic antibiotics have been shown to be of no benefit when aggressive irrigation and d�bridement have been provided. Discussion Distal phalanx fractures are the most incessantly seen fractures of the hand, with the tuft being the most common web site. Stevenson J, McNaughton G, Riley J: the use of prophylactic flucloxacillin in treatment of open fractures of the distal phalanx within an accident and emergency division: a double-blind randomized placebo-controlled trial, J Hand Surg Br 28:388�394, 2003. Both mechanisms can avulse the insertion of the flexor tendon on the distal phalanx. What To Do: Have the affected person try to close the fingers against the palm in a unfastened fist. The radiograph is normally normal, although sometimes a small avulsion fracture could also be seen on the proximal volar facet of the distal phalanx. A protecting dorsal splint (positioned for best comfort) incorporating the adjacent finger and extending to the mid-forearm may be utilized to cut back ache and help stop additional harm. What Not To Do: Do not assume a easy sprain exists due to negative radiographs. Discussion Avulsion of the insertion of the flexor digitorum profundus tendon outcomes from the sudden compelled extension of a finger during resisted flexion of the digit with the metacarpophalangeal joint in extension. It could have appeared abruptly, been present for years, or fluctuated, suddenly resolving and gradually returning in just about the identical place. The affected person usually first notices it when a minor injury brings it to their consideration and frightens them. There is often little tenderness, inflammation, or interference with operate, but ganglion cysts may be bothersome with signs that include pain, paresthesias, limitation of motion, or weak point. These cysts are normally self-evident and customarily no larger than 2 cm in diameter. They are gentle and ballotable and appear on the dorsal or volar facet of the wrist. It is pointless to get hold of a radiograph of a traditional, asymptomatic ganglion cyst. Although most ganglions could be recognized simply on bodily examination, ultrasonography may be useful in diagnosing a small or questionable lesion. Transillumination with an otoscope mild will show its clear cystic nature. Explain to the patient that this is a fluid-filled cyst, spontaneously arising from bursa, ligament, or tendon sheath and poses no specific hazard. Treatment choices embody the next: (1) doing nothing; (2) draining the contents of the cyst with an 18- or 22-gauge needle to reduce its dimension, with or with out injecting it afterward with a corticosteroid; or (3) arranging for a surgical excision, which will present a definitive pathologic diagnosis. If the affected person has signs, including pain or paresthesias, or is disturbed by the appearance, aspiration with or without injection of a corticosteroid is effective, without recurrence, in 27% to 67% of patients. Surgical therapy entails whole ganglionectomy, with elimination of a modest portion of the connected capsule. With an 18- or 22-gauge needle on a 10-mL syringe, aspirate the mucinous contents. Optionally, instill a longacting corticosteroid, such as 1 mL betamethasone (Celestone Soluspan) or 10 to 20 mg of triamcinolone (Kenalog-10), together with 2 mL of 0. When injecting a corticosteroid after aspiration, a hemostat is used to stabilize the needle whereas the syringe is changed. Discussion Ganglion cysts are outpouchings of bursae, ligament, or tendon sheaths, with no clear trigger and no relation to nerve ganglia. This mucin dissects alongside the connected joint ligament and capsule to form capsular ducts and dilatations (lakes) of mucin. Their viscous mucin consists of hyaluronic acid, albumin, globulin, and glucosamine. A dorsally located ganglion of the distal interphalangeal joint is also called a mucous cyst. Any joint may be affected, often of the lower limb, together with the ankle, knee, and tarsal joints, however commonest is the metatarsophalangeal joint of the good toe (podagra). There is usually no fever, rash, or different sign of systemic illness, though lowgrade fever, leukocytosis, and an elevation of the erythrocyte sedimentation price could happen. The affected person could have predisposing elements that enhance his threat for creating gout, corresponding to weight problems, moderate to heavy alcohol consumption, high blood pressure, diabetes, and abnormal kidney perform, or he may be taking certain medication, together with thiazide diuretics, low-dose aspirin, and tuberculosis medicines (pyrazinamide and ethambutol). In addition to ruling out an infection, look under the microscope for crystals within the joint fluid. Excruciating pain may require one dose of narcotics while the anti-inflammatory medicine take impact. They must be used with warning or under no circumstances in patients with any of the following: vital renal impairment (creatinine > 2), poorly managed congestive coronary heart failure, historical past of or active peptic ulcer disease, anticoagulation remedy, or hepatic dysfunction. Care should be utilized in patients with diabetes, but in current years, corticosteroids have been used more typically in older patients with multiple comorbid circumstances due to their low-toxicity profile. For a monoarticular flare-up, an intra-articular injection of a long-acting corticosteroid is commonly the safest treatment. Delay injecting corticosteroids in to the joint till the potential of infection is eradicated (see Chapter 120). After draining as much fluid as possible from the joint, using aseptic methods, inject betamethasone (Celestone Soluspan), 1 mg (small joints) to four mg (large joints), or methylprednisolone (Depo-Medrol), about 20 to forty mg combined in an acceptable volume (depending on joint size) of bupivacaine (Marcaine) zero. Start with 20 to forty mg of prednisone (Deltasone) after which taper throughout 8 days. An various therapy for acute gouty arthritis throughout the first 12 to 24 hours of an assault is colchicine, 0. After these most doses, no more colchicine ought to be prescribed for 1 week to avoid toxicity. At excessive doses, colchicine is bone marrow�suppressive and with renal insufficiency or sufferers taking cyclosporine or statins, colchicine can cause neuromyopathy. It ought to nonetheless be used with warning in older sufferers with reduced renal operate. At times, the dangers of certain therapies could outweigh the benefits, especially in elderly sufferers. Instruct the patient to elevate and rest the painful extremity, apply ice packs, and arrange for follow-up. In gouty arthritis, cold functions, along with being a useful adjuvant therapy, are helpful for discriminating gout from different forms of inflammatory arthritis. Topical ice has been shown to assist relieve joint ache in sufferers with gouty arthritis however not in sufferers with different inflammatory arthritides. Patients should be informed about the elements contributing to their hyperuricemia, corresponding to obesity, a high-purine diet, regular alcohol consumption, and diuretic therapy, which may all be correctable. Some physicians advocate utilizing this remedy in patients who experience greater than 4 attacks per yr.