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Field and Weiss (1989) proposed that the ability to follow directions and judgement of the rate and amount of intake are affected by cognitive status allergy testing list buy nasonex nasal spray. These cognitive-behavioural de cits contribute to dysphagia in unpredictable ways allergy medicine nose spray purchase nasonex nasal spray canada, as swallowing has a voluntary as well as a re exive component (Field and Weiss allergy medicine i can take while pregnant discount 18 gm nasonex nasal spray otc, 1989) allergy shots for pet dander nasonex nasal spray 18gm with visa. Ylvisaker and Logemann (1985) have stated that severe dysphagia may occur in the presence of a mild physiological de cit due to cognitive-behavioural factors allergy medicine 6 hours relief buy 18gm nasonex nasal spray amex. In this way cognitive-behavioural de cits can be iden ti ed and appropriate management strategies be determined to reduce the impact of such issues on dysphagia outcome allergy testing experience discount nasonex nasal spray. Subsequently, almost 80% of participants were unable even to orientate their head to the spoon upon presentation of food. Given the severity of tonal and postural impairment resulting in head and neck instability, it is not surprising that this population also had signi cant impairment in respira tory, laryngeal, lip, jaw and tongue function (Morgan et al. The inability to achieve respiration adequate for phonation was noted in almost 90% of participants, and this, alongside issues of poor laryngeal closure on the clinical bedside evalua tion, resulted in an inadequate cough re ex. Reduced facial tone may lead to food collecting in the cheeks, and large amounts of oral residue, placing the individual at an increased risk of passive food loss into the airway, or actively inhaling material. Problems with lip seal make removing the food from the spoon dif cult, and these children also com monly display inactivity of the lips during sucking, munching or chewing, affecting intraoral pressure and bolus transit. Predictive factors for dysphagia and long-term dysphagia prognosis Miller and Groher (1997) recognize that one of the most dif cult aspects of working with neurogenic dysphagia is the diversity of the nature and extent of swallowing de cits that can arise even in patients with similar neuropathology. Seven children had haematoma, two presented with cerebral oedema and two with multifocal or diffuse injuries. The dysphagia outcome for children with brain stem impairment however appears less favourable than for those with neurologi cal lesions con ned to the cerebrum. Fluid supplementation was still required by percutaneous endoscopic gastrostomy at 10 months after injury. Rowe (1999) has also reported on a paediatric case with brain stem injury that had longer term persistent swallowing de cits than children with other types of neuropathology. A prognosis of long-term rehabilitation prior to the return to oral feeding after brain stem injury is not surprising given the po tential interruption of the complex relationship between the cranial nerve nuclei, nerve tracts and reticular interneurons found within the brain stem for the control of swal lowing. Disruption of this relationship has been reported to potentially result in severe dysphagia that is resistant to spontaneous recovery in the adult population (Huckabee and Cannito, 1999). Whilst the complication of mal nutrition can be successfully offset in the majority of cases by supplemental nutri tion, the management of aspiration and subsequent respiratory compromise is more complex. Due to the shared anatomy of swallowing and respiration, problems related to swallowing can manifest in respiratory symptoms, and swallowing problems can exacerbate respiratory dif culties (Brodsky, 1997). Given the inter-relationship be tween respiration and swallowing, determining the cause of dysphagia in a child with breathing problems is complex. There are two main ways in which dysphagia and aspiration may lead to respira tory disease. The second is aspiration of gastric contents into the trachea follow ing gastroesophageal re ux or an episode of vomiting (McColley and Carrol, 1994; Morton et al. Gastroesophageal re ux without aspiration has also been im plicated in respiratory disease (McColley and Carrol, 1994), with clinical symptoms such as coughing, wheezing and recurrent pneumonia (Bauer et al. Taniguchi and Moyer (1994) suggest that if there are respiratory problems with gastroesopha geal re ux, then oropharyngeal problems are likely to coexist. There is much debate regarding which mechanism of aspiration is most commonly associated with more serious consequences. They also found that patients were at even higher risk of severe respiratory tract infections, and likely gastrostomy and fundoplication placement, if gastroesophageal re ux and aspiration of stomach contents were present in addition to oropharyngeal dysphagia (Morton et al. Taniguchi and Moyer (1994) also found that factors associated with an increased risk of pneumonia in a group of 142 patients with dysphagia of mixed aetiology were: presence of oropharyngeal aspira tion, presence of gastroesophageal re ux, and the presence of a tracheostomy tube. This fact is not surprising given that the development of respiratory problems is linked to the acidity of the material aspirated. A relatively small volume of aspirate can lead to signi cant respiratory issues if the pH is low, whereas larger volumes of neutral pH aspirate can be tolerated (Raidoo et al. The texture of the food/ uid aspirated has also been linked to respiratory outcome in children. Taniguchi and Moyer (1994) found that children who aspirated pureed consistencies had nine times the risk of developing pneumonia compared to children who did not aspirate this consistency. Children who aspirated thickened liquids had the second greatest risk of developing pneumo nia and children who only aspirated thin liquids did not have a statistically signi cant increase in pneumonia risk (Taniguchi and Moyer, 1994). The clinical manifestations of dysphagia and/or aspiration differ between in fants and children (Loughlin and Lefton-Greif, 1994). They are rarely noted in older children who present more frequently with cough, congestion, wheezing, bronchitis, atelectasis and pneumonia (Loughlin and Lefton-Greif, 1994). The most serious clinical mani festation of aspiration is bacterial pneumonia; however, other chronic symptoms can be persistent and frustrating such as coughing and wheezing (McColley and Carrol, 1994). Some children presenting with chronic aspiration have been found to present with wheezing that cannot be remedied with bronchodilator therapy. Symptoms of aspiration with respiratory complication include: apnea, stridor or hoarseness, re current episodes of fever and dyspnea, atelectasis or in ltrates noted on chest x-ray, noisy congested breathing, coughing, and choking on feeds (Loughlin and Lefton Greif, 1994; McColley and Carrol, 1994). Some populations with already compromised respiratory function are at par ticular risk of further respiratory complications subsequent to dysphagia. The reader is also referred to Chapter 4 for further discussion of the interplay between respiration and swallowing. It is inappropriate, however, to assume that the underlying cause of dysphagia is a result of either the primary or secondary medical diagnoses alone. Reilly and Carr (2003) provided an example of this error in reporting a paediatric case whose food refusal was initially related to his primary diagnosis of developmental disability, but later correctly de termined to be due to a lodged foreign body that was causing the child great irrita tion. It is also clear from the current chapter that many of the clinical characteristics, signs and symptoms of dysphagia are similar across medical populations. Extra caution must also be used when interpreting from these signs in a paediat ric population that is often unable to communicate its own dif culties, and whose underlying problems may be further compounded by a variety of developmental stressors. In conclusion, it is critical that the management of children with dysphagia involve multiple professionals working within a developmental framework. In this way, a comprehensive picture of the presenting feeding and swallowing issues can be documented for a particular child, enabling optimal assessment and treatment planning, and leading to optimal dysphagia outcomes for each individual. Benjamin B, Inglis A (1989) Minor congenital laryngeal clefts: diagnosis and classi cation. Blissett J, Harris G, Kirk J (2000) Growth hormone therapy and feeding problems in growth disorders. Blissett J, Harris G (2002) A behavioural intervention in a child with feeding problems. Brodsky L (1997) Dysphagia with respiratory/pulmonary presentation: assessment and management. Budden S, Meek F, Henighan C (1990) Communication and oral motor function in Rett syn drome. Caouette-Laberge L, Plamondon C, Larocque Y (1996) Subperiosteal release of the oor of the mouth in Pierre Robin sequence: experience with 12 cases. Chatoor I, Conley C, Dickson L (1988) Food refusal after an incident of choking: a post traumatic eating disorder. Dahl M, Sundelin C (1986) Early feeding problems in an af uent society: categories and clinical signs. DiScipio W, Kaslon K, Ruben R (1978) Traumatically acquired conditioned dysphagia in children. Field D, Garland M, Williams K (2003) Correlates of speci c childhood feeding problems. Fischer-Brandies H (1989) Vertical development of the jaw in cases of trisomy 21: Interac tions of form and function. Haig D, Wharton R (2003) Prader-Willi syndrome and the evolution of human childhood. Kawahara H, Dent J, Davidson G (1997) Mechanisms responsible for gastroesophageal re ux in children. Kohda E, Hisazumi H, Hiramatsu K (1994) Swallowing dysfunction and aspiration in ne onates and infants. Kovesi T, Rubin S (2004) Long-term complications of congenital esophageal atresia and/or tracheoesophageal stula. Kramer S, Monahan-Eicher P (1993) the evaluation of pediatric feeding abnormalities. Lachman R, Funamura J, Szalay G (1981) Gastrointestinal abnormalities in the Cornelia de Lange syndrome. Li H-Y, Lo L-J, Chen K-S, Wong K-S, Chang K-P (2002) Robin sequence: review of treat ment modalities for airway obstruction in 110 cases. MacDonald A, Holden C, Harris G (1991) Nutritional strategies in cystic brosis: Current issues. Acute clinical characteristics of paediatric dys phagia following traumatic brain injury. The Normal Acquisition of Oral Feeding Skills: Implications for Assess ment and Treatment. Noerr B (2003) Current controversies in the understanding of necrotizing enterocolitis. Odman C, Kiliaridis S (1996) Masticatory muscle activity in myotonic dystrophy patients. Orenstein S, Shalaby T, Putnam P (1992) Thickened feedings as a cause of increased cough ing when used as therapy for gastroesophageal re ux in infants. Papargyriou G, Kjellberg H, Kiliaridis S (2000) Changes in masticatory mandibular move ments in growing individuals: a six-years follow-up. In Caruso A, Strand E (eds) Clinical Management of Motor Speech Disorders in Children. Reilly S, Carr L (2001) Foreign body ingestion in children with severe developmental dis abilities: a case study. Reilly S, Skuse D (1992) Characteristics and management of feeding problems of young chil dren with cerebral palsy. Reilly S, Skuse D, Poblete X (1996) Prevalence of feeding problems and oral motor dysfunc tion in children with cerebral palsy: a community survey. Robin P (1923) La chute de la base de la langue consideree comme une nouvelle cause de gene dans la respiration naso-pharyngienne. Rogers B (2004) Feeding method and health outcomes of children with Cerebral Palsy. Romero R, Chaiworapongsa T, Espinoza J (2003) Micronutrients and intrauterine infection, preterm birth and the fetal in ammatory response syndrome. Varan B, Tokel K, Yilmaz G (1999) Malnutrition and growth failure in cyanotic and acy anotic congenital heart disease with and without pulmonary hypertension. Antroduodenal motility in neurologically handicapped children with feeding intolerance. Before treatment and management can com mence, however, there is a need for a thorough assessment of swallowing function. As detailed in Chapter 2, the infant swallow and the adult swallow are quite differ ent and warrant individual discussions in their own right. Once cannot assume that assessment techniques that are suitable for adults will also be suitable for babies, infants and children. This chapter will discuss both (a) clinical assessments and (b) instrumental assessment techniques that are suitable for use with babies, infants and children. The ultimate goal of the clinical oral assessment is to de ne the pathophysiology and the extent of the feeding dif culties. In this problem-solving process, the evaluation of the oral cavity and its functions by observation plays a major role, and should occur prior to instrumental assessment. The feeding specialist must have a thorough understanding of normal function of the many interacting systems involved in feeding. In the clinical oral feeding evalu ation, oral anatomy, motor skills, re ex activity, responsivity and swallowing are examined. With this information, referrals can be made for further diagnostic test ing and multidisciplinary management where a speci c treatment plan can be devel oped. The clinical oral examination should therefore always be the initial assessment scheduled in a team evaluation. Oral structures are examined for malformations and for abnormalities of muscle tone and muscle mass. The lips, cheeks, jaw, tongue, hard and soft palate are examined at rest and during spontaneous movement. Palatal and labial clefts, micrognathia, deviant dental oc clusion, ankyloglossia and trismus are some of the most frequently seen anomalies. Assessment of oral motor function Oral motor skills have been described extensively in anatomy text books, develop mental and rehabilitation literature (Morris, 1982).

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The Marchetti classification is almost self explanatory and due to the avoidance of confusing terminology in our opinion seems to be more up to date allergy treatment in ayurveda purchase nasonex nasal spray 18 gm free shipping. Both types may have defects of the pars interarticularis allergy symptoms vitamin c cheap nasonex nasal spray 18gm without prescription, yet they present different pathologic processes [30] allergy symptoms rash on arms purchase nasonex nasal spray 18 gm with visa. It was modified in 1989 by Wiltse and Rothmann [119] to include an extra sub type of spondylolisthesis resulting from prior surgery allergy medicine 3 month old purchase nasonex nasal spray us. Clinical Presentation Patients with spondylolysis Patients with spondylolysis or spondylolisthesis may be asymptomatic and never or spondylolisthesis may present for medical evaluation allergy forecast in dallas order nasonex nasal spray with visa. Those that seek medical advice do so with a vari be clinically asymptomatic ety of symptoms allergy testing child buy nasonex nasal spray with amex. By carefully scrutinizing the information yielded by the patient, an experienced physician can draw conclusions about the underlying pathophysiologic mechanisms. Occasionally, an asymptomatic adult may develop back or radicular pain as a Make sure that the result of proximal lumbar disc pathology, bringing the spondylolisthesis to light radiographically obvious for the first time. Despite con result from abnormal ventional beliefs, the hypothesis that degenerative spondylolisthesis is associated load distribution with increased motion remains to be proven. The bandwidth and intensity of pain is variable and may be of sud den onset, chronic or intermittent. Patients may note aggravation with position transition such as changing from sitting to standing [88] and are often completelypainfreeonrest. Theleg pain can be distinguished as: referred radicular this depends on the presence of a true neural (mostly foraminal) compromise. Neu in spondylolisthesis rogenic claudication is produced by spinal stenosis secondary to slippage and hypertrophy of the ligamentum flavum and facet joints encroaching into the spi nal canal. Pain along the buttocks and both legs may occur with standing or walking and is frequently associated with dysesthesia, numbness or weakness of the legs. In children, most high-grade developmental spondylolisthesis develops significant slippage during the adolescent growth period [33, 51], and this is usually when symptoms occur [36]. Several risk factors for this progression such as age, sex, spina bifida and dys plasia have been identified [12]. Back pain in young children and adolescents always raises suspicion of an underlying spondylolysis. Adolescents with symp 738 Section Spinal Deformities and Malformations tomatic high-grade spondylolisthesis often have sciatic pain that can develop into a sciatic crisis known as: Phalen-Dixon sign Young patients may present this includes sciatic pain, vertical sacrum and pelvis, lumbosacral kyphosis, with a sciatic crisis known tight hamstrings, and an unusual pelvic waddling gait [33, 51]. Physical Findings Patients should very Physical examination should be performed to distinguish referred from radicu carefully be neurologically lar symptoms, to document spinal sagittal alignment and spinal mobility and to assessed establish the presence of any neurologic deficits. However, frequent findings are: tight hamstrings sensorimotor deficits pain on backward bending and rotation (often facet joint pain) pain on forward bending (often discogenic pain) pain on extension from the forward bent position limitation of walking distance Pain in adults with Pain provocation on specific movements can indicate the source of the pain. However, these findings are variable and the frequently due to secondary actual prediction of the pain source is not very reliable. Radiographs should therefore not be overinterpreted, as numerous spinal pathologies can give rise to back and/or leg pain. Osteoarthritis of the hip is found in about 15% of patients with degenerative spondylolisthesis and commonly radiates to the anterior thigh and thus mimics Degenerative spondylolis an L3 or L4 radiculopathy [5]. Syndromes which are associated with spondylolisthesis are: neurofibromatosis I [16] Marfan syndrome [99, 122] Tricho-rhino-phalangeal syndrome [103] Ehlers-Danlos syndrome [76] myelomeningocele [101] Spondylolisthesis associated with abnormal bone and/or soft tissue constraints is rare and reports on these remain mostly anecdotal. Appro priate treatment of these patients, who more often than not have concomitant mas sive degenerative changes, will depend on the amount of slippage and symptom atology as well as the neurologic findings. However, functional views have failed to reliably demonstrate an instability [25] and the motion within an olisthetic segment can even be less than in a normal segment. Measurements of spondylolisthesis a the angle between a line across the cranial border of S1 and the horizontal plane comprises the sacrohorizontal angle. This has clinical implications insofar that there is a good chance of successful conservative management of a fresh pars defect or imminent stress fracture, while older lesions usually do not heal with non-opera tive management. In adults, where acute lesions are rarely found, the sensitivity of a bone scan is poor [81]. Normally, the usual gantry is angled perpendicularly to the pars defect increasing the risk of overlooking a pars defect. Conser vative treatment with a lumbar brace treat ment including the right thigh for8 weeks was started (c). The slipped vertebra often causes a secondary degeneration of the upper adjacent intervertebral disc. In cases with mild disc degeneration, the question arises whether the upper level should be included. In this case, provocative discography (see Chapter 10) can be helpful in deciding whether the upper disc level is pain ful and should therefore be included in the fusion. While nat a benign condition ural history is benign in low-grade adult spondylolisthesis, there is a high ten with little progression dency for slip progression in children. The risk of slip progression is very high in the presence of a lumbosacral deformity and a rounded sacrum dome, which often leads to a high A rounded sacral dome pre grade slip and a lumbosacral kyphotic deformity. While progressive deformity might well occur due to increase in degeneration at the slipped seg ment, the incidence and magnitude of such progression is small [44]. In only 30% of these cases does slippage progress, and about 75% of the patients who are initially neurologically intact do not deterio rate over time [58]. In view of this, treatment is dependent on the presence of a neurologic deficit either caused by a foraminal or a central stenosis. Treatment should therefore also take into account severity and duration of symptoms and comorbidities. With regard to the aforementioned aspects an etiology-based recommenda tion of treatment modality can be given (Table 4). Conservative Treatment Options In general, the vast majority of patients with spondylolisthesis can be treated the vast majority of spondy non-operatively (Table 5). Favorable indications for non-operative treatment no neurologic deficit high patient comorbidity tolerable pain threshold improvement by exercise program short duration of symptoms improvement by brace treatment In patients without this is followed by a therapeutic exercise program with paraspinal and abdomi neurologic deficit, nal strengthening to improve muscle strength, flexibility, endurance and balance asufficientconservative (see Chapter 21). In these cases, non-operative management is not equally suc cessful when compared to mechanical low back pain. The non-operative treat ment can be supported by spinal injections (see Chapter 10)toreduceinflam mation and thus temporarily or even permanently eliminate leg pain: epidural blocks spondylolysis block nerve root blocks In patients with chronic recurrent back and leg pain a sufficient period of conser vative management should be performed before operative options are seriously contemplated. It is essential that the surgeon is certain that the symptoms are in fact a result of the slippage. One of the most important measures for dealing with pain is the stretch ing of the hamstrings. These exercises will improve the clinical condition in the vast majority of the cases. Spondylolisthesis Chapter 27 747 In young patients with an acute pars defect, a lumbar brace treatment including An acute pars defect can be onethighisavaluabletreatmentoption. Indications for surgery Absolute indications Relative indications progressive neurologic defits minor, non-progressive neurologic deficits slip progression in children/adolescents radicular and claudication symptoms high-grade spondylolisthesis in children mechanical low-back pain non-responsive severe lumbosacral kyphosis with gait to non-operative care disturbance High-grade developmental spondylolisthesis in adolescents should almost Progressive slips in always be treated operatively. Those presenting with a sciatic crisis known as the children should be Phalen-Dixon sign need immediate medical attention in the form of intravenous treated operatively analgesics, bedrest and close neurologic monitoring. If the severe pain does not subside quickly or neurologic deficit is observed, early surgical management shouldbestrivedfor. While the young, otherwise healthy adult will biomechanically benefit from correction of deformity parameters and realignment of the spine with the sacrum, the elderly patient with comorbidity may only need decompression. The decision to recom spondylolisthesis 748 Section Spinal Deformities and Malformations mend surgery to an adult patient with spondylolisthesis must therefore be indi vidualized very carefully. Overall direct osteosynthesis seems to be a compara tively safe and effective treatment method, independent of which method is uti lized in cases with spondylolysis and fresh pars defects [19, 124]. While neurologic deficit is a definite indication for decompression, there is an ongoing discussion as to whether in the face of radicular symptoms decompression is always necessary [44]. Long-term follow-up studies have shown that especially in children repositioning of the slippage by instrumentation can improve leg pain very soon after surgery [46]. However, with the advent of pedicular fixation devices, many spine surgeons have now changed to an instrumented fusion because it facilitates aftertreatment [11, 13, 43, 47, 92, 105]. Outcome of instrumented While the surgeon may well have the impression that instrumentation gives good fusion is not shown primary stability and allows for a more precise realignment of the spinal column, to be superior to studies randomizing isthmic spondylolisthesis patients with and without pedicle non-instrumented fusion screws have not shown an improved fusion rate or improved clinical outcome with reduction and instrumentation [8, 62, 69]. Direct spondylolysis repair a Isthmic spondylolisthesis at the level of L4/5 (arrow). The transverse processes should be thoroughly denuded and decorticated, along with the lateral aspect of the facet joint and pedicle (see Chapter 20). Bone is usually obtained from the iliac crest, though this may of course increase morbidity. Slip Reduction the treatment of high-grade spondylolisthesis differs between children and adults, asdoesthatoflow-andhigh-gradeslipsinadults. The aim is to decom press neural structures, decrease the lumbosacral kyphosis and facilitate fusion. Especially when repositioning and/or distraction is performed, an is recommended when interbody structural support of the anterior column is crucial [11]. In cases reduction and/or where the anterior column has not been addressed biomechanically, fusion rates distraction is performed for posterolateral fusions vary from 100% [11, 29, 92] to as low as 33% [41, 50, 111]. Surgery was performed to realign the spine by means of sacral dome osteotomy (for technique see Fig. While disc height may thereby be restored and kyphosis diminished, there is ongoing discussion as to whether an adequate repositioning and thus improvement of sagittal alignment of the spine can be achieved by a single anterior procedure, with or without instrumentation. Also, because nerve root and dural sac are not decompressed before the repositioning maneuver, there is a high likelihood of neurologic injury. In the lumbar spine the anterior technique usually involves a retroperitoneal approach, with its attendant complications such as possibility of vascular injury, damage of the sympathetic plexus with subsequent retrograde ejaculation in males, as well as damage to retro and intraperitoneal structures. Spine surgeons performing this approach should therefore either be able to manage possible complications themselves or have very fast access to expertise. Circumferential stability offers all the advantages of both the aforementioned Circumferential arthrodesis techniques, yet obviously also incorporates the possible complications. This technique allows to distract between L4 and S1, which facilitates the reduction. In selected cases, the L4 screws can be removed at the end of the operation or alternatively 12 weeks later, which leaves the motion segment L4/5 intact [87]. In adults the L4/5 disc In adults with marked slips of L5/S1, the adjacent L4/5 segment frequently is often degenerated exhibits significant degenerative changes. In these cases, a fusion of L4 to S1 is and requires inclusion indicated because the L4/5 segment often rapidly decompensates after the L5/S1 in the fusion fusion. In a second stage, the posterior approach allows realignment of the spine after L5 pedicles, facets and laminar arch have been removed bilaterally. This technique consists of a bilateral osteotomy of the sacral dome, which allows the reduction of the slip without distraction (Fig. This demanding procedure should be carried out Spondylolisthesis Chapter 27 755 a c e Figure 7. Reduction of high-grade spondylolisthesis with sacrum dome osteotomy a the pedicles of L4, L5 and S1 are instrumented with pedicle screws. It is important to note that neu romonitoring is not absolutely reliable, because paresis of the nerve root can occur even hours after the surgery. Complications Typical complications As with all surgical procedures, patients surgically managed for spondylolisthe encountered are neurologic sis must receive the best outcome with low exposure to problems and complica injuries and non-union tions. In situ fixation for degenerative low-grade slippage in the adult will have a markedly lower risk of attaining neurologic impairment than complex reconstructive surgery of the adolescent spine in spondyloptosis. As with all neurologic complications, these need to be accurately assessed and diagnostic imaging should occur rap idly. In general for any surgeon, the decision for or against revision surgery is among the most difficult to make. It is therefore prudent to involve a further, less biased surgeon to assess the patient as well as the radiographic parameters and decide for or against revision together. As most slippages are lateral radiographs are the mainstay for the initial as asymptomatic, the true incidence of the condition sessment. Treatment decision will stabilizing elements and the disc is confronted with ultimately be based on the age of the patient, excessive shear. The dissociation of the anterior symptoms, etiology as well as the degree of slip and posterior column therefore ultimately results page. Acute pain should be controlled with initial a motion segment, trauma, tumors, and rare syn rest, anti-inflammatory and/or pain-modulating dromes or systemic bone disease.

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Physiologic consequences resulting from copper deficiency include defects in connective tissue that lead to vascular and skeletal problems allergy shots given to cats generic nasonex nasal spray 18gm without prescription, anemia associated with defective iron utilization allergy symptoms weather changes discount nasonex nasal spray 18gm on-line, and pos sibly specific aspects of central nervous system dysfunction (Harris allergy symptoms 6 weeks generic nasonex nasal spray 18gm amex, 1997; Turnlund allergy medicine and depression discount nasonex nasal spray 18gm otc, 1999) allergy medicine under 2 years old purchase nasonex nasal spray with american express. Some evidence suggests that immune and cardiac dysfunction occurs in experimental copper deficiency and the development of such signs of deficiency has been demonstrated in infants (Graham and Cordano allergy forecast rapid city sd buy nasonex nasal spray master card, 1969; Olivares and Uauy, 1996; Turnlund, 1999). Physiology of Absorption, Metabolism, and Excretion Metabolism of copper in humans relies on the intestine for con trol of homeostasis as the capacity for renal copper excretion is limited. Nearly two-thirds of the body copper content is located in skeleton and muscle, but studies with stable isotopes have shown that the liver is a key site in maintaining plasma copper concentra tions (Olivares and Uauy, 1996; Turnlund et al. Copper has a higher binding affinity for proteins than all other divalent trace elements (da Silva and Williams, 1991). Consequently, precise con trol of intracellular copper trafficking is needed to regulate how it is donated to appropriate sites. Some absorption may occur in the stomach where the acidic environment promotes copper solubility by dissociation from copper-containing macromolecules derived from dietary sources (Harris, 1997; Turnlund, 1999). Both saturable-mediated and nonsaturable-nonmediated (possibly paracellular) transepithelial copper movements have been reported. The extent of copper absorption varies with dietary copper intake (Turnlund, 1998). It ranges from over 50 percent at an intake of less than 1 mg/day to less than 20 percent above 5 mg/day. Copper is released via plasma to extrahepatic sites where up to 95 percent of the copper is bound to ceruloplasmin (Turnlund, 1999). The biological role of ceruloplasmin in copper metabolism has been widely investigated. The autosomal recessive disorder in humans, aceruloplasminemia, does not produce abnormal copper metabo lism, thus contradicting a role for the protein in copper delivery to cells. Clinical Effects of Inadequate Intake Frank copper deficiency in humans is rare, but has been found in a number of special conditions. Supplementation with copper resulted in rapid increases in serum copper and ceruloplasmin concentra tions. Symptoms accompanying the copper deficiency included normocytic, hypochromic anemia, leukopenia, and neutropenia (Fujita et al. Two patients had neutropenia, one had macrocytic, normochromic anemia, and some had bone abnormalities includ ing reduced bone density. Neutrophil counts normalized and bone abnormalities improved after copper supplementation. Although serum copper and ceruloplasmin concentrations of these men did not fall to the deficient range in 42 days and clinical symptoms did not appear, these effects might be expected had the low copper diet been continued. Results of depletion studies in laboratory animals have led to in terest in a number of conditions in humans that may be associated with marginal copper intake over a long period. Insufficient data are available at this time to establish whether these conditions are related to dietary copper. This effect was not observed in other subjects or in a number of other studies with this or lower levels of dietary copper. In one study, blood cholesterol concentration decreased with lower dietary copper (Milne and Nielsen, 1996), and in a copper supplementation study investiga tors found increased blood cholesterol concentrations with supple mentation (Medeiros et al. Heart beat irregularities were reported in some studies, and inves tigators linked them to dietary copper intake (Milne, 1998). How ever, heart beat irregularities are common in normal, healthy people, and other studies with lower copper intake demonstrated that such irregularities, monitored during copper depletion and repletion, were common at all intake levels of dietary copper (Turnlund et al. However, the myo cardial changes observed in copper-deficient animals are very dif ferent from those of ischemic heart disease in humans (Danks, 1988). Coronary artery resistance is decreased in copper-deficient animals, but it is increased in ischemic heart disease. Several other clinical observations deserve further investigation, but there is insufficient evidence to link them to marginal copper status. One study reported a negative correlation between ceruloplasmin con centration and blood pressure during a hand grip exercise (Lukaski et al. The role of copper as an antioxidant has led to interest in the possibility that copper deficiency impairs antioxidant status (Johnson et al. Changes in catecholamine metab olism have been investigated, but results are inconsistent (Bhathena et al. However, except when diets are deficient in copper, they do not reflect dietary intake and may not be sensitive to marginal copper status. Platelet copper concentration and cytochrome c oxi dase activity may be more sensitive to marginal intakes of dietary copper than plasma copper or ceruloplasmin concentration, but they have been measured in very few studies to date. No single indicator provides an adequate basis on which to estimate the copper requirement. Serum Copper Concentrations Serum copper concentration is a reliable indicator of copper deficiency, falling to very low concentrations in copper-deficient individuals. Serum copper concentration returns to normal within a few days of copper supplementation (Danks, 1988). While serum copper concentration is an index of copper deficiency, it does not reflect dietary intake except when intake is below a cer tain level. Above this level, supplementation with copper does not increase serum copper concentration. Serum copper concentration increases under a number of conditions due to increased concen trations of ceruloplasmin. Ceruloplasmin Concentration Ceruloplasmin concentration is also a reliable indicator of copper deficiency. Ceruloplasmin carries between 60 and 95 percent of serum copper, and changes in serum copper concentration usually parallel the ceruloplasmin concentration in the blood. Cerulo plasmin, too, falls to low concentrations with copper deficiency, far below the lower end of the normal range of 180 mg/L, and it responds quickly to repletion (Danks, 1988). The dietary copper intake at which ceruloplasmin concentration no longer in creases in response to increased dietary copper might be consid ered the copper requirement for ceruloplasmin synthesis. Cerulo plasmin is an acute phase protein and increases markedly with a number of diseases, including liver disease, malignancy, inflamma tory diseases, myocardial infarction, and a variety of infectious diseases (Mason, 1979). With any of these conditions, copper deficiency might not be diagnosed on the basis of serum copper or cerulo plasmin concentrations. It does not increase with the conditions that increase serum copper and ceruloplasmin concen trations. Platelet Copper Concentration and Cytochrome c Oxidase Activity Two studies in women suggest that both platelet copper concen tration and platelet cytochrome c oxidase activity may respond more rapidly to low dietary copper than the indicators discussed above. Platelet copper concen tration increased after repletion, but platelet cytochrome c oxidase activity did not. Moreover, an intervening vitamin C supplementation period added another variable to the data interpretation. Therefore, the above research suggests that platelet copper concentration and platelet cytochrome c oxidase activity, when measured in controlled studies, may be more sensitive to changes in copper dietary intake. Above those levels of dietary intake, urinary copper does not respond to increases in dietary copper. In controlled studies, a decline in urinary copper excretion can be used as supporting evidence for inadequate intake. Leukocyte Copper Concentration Leukocyte copper concentration was found to decline along with other indexes of copper status in one study (Turnlund et al. Too few data are currently available to use it for establishing dietary recommendations for copper. Lysyl Oxidase Activity Lysyl oxidase activity in the skin, which declined with low dietary copper and increased with repletion, is potentially a useful indica tor of copper status (Werman et al. It is not known if lysyl oxidase activity reflects dietary intake at higher levels of dietary copper in humans. Because data are available from only one study, it cannot yet be used as an indicator for estimating copper require ments. Copper Balance Balance studies have been used in the past to estimate dietary recommendations. Numerous copper balance studies in humans have been conducted over a wide range of intakes (Mason, 1979). Unfortunately, there are a number of problems with this approach, as reviewed by Mertz (1987). Copper balance, which can be achieved over a broad range of dietary copper intakes, reflects prior dietary intake; thus long adaptation is required for results to be meaningful. Such studies are prone to numerous errors, and data from some studies would sug gest that an unacceptable amount of copper would accumulate over time if these levels of retention were continued. Factorial Analysis One approach to estimating minimum dietary mineral require ments is by the factorial method. Obligatory losses, the amounts of an element excreted with no dietary intake, are determined, and then the amount needed in the diet to replace these obligatory losses is calculated. Obligatory losses include urinary losses, gastro intestinal losses, sweat, integument, hair, nails, and other miscella neous losses such as menstrual and semen losses. For copper, as for other elements, reliable values for many of these losses are not avail able. However, sufficient data are available to make reasonable esti mates; therefore, this method can be used in support of estimates of dietary copper requirements made by other methods. The bioavailability of copper is influenced markedly by the amount of copper in the diet. In addition, excretion of copper into the gastrointestinal tract regulates copper retention. As more copper is absorbed, turn over is faster and more copper is excreted into the gastrointestinal tract (Turnlund et al. This efficient homeostatic regulation of absorption and retention helps protect against copper deficiency and toxicity. Zinc Zinc intakes, well in excess of the amount normally found in the diet, can decrease copper absorption in adults (Turnlund, 1999) (see Table 12-7). In one case report, an infant who was given 16 to 24 mg/day of zinc developed copper deficiency (Botash et al. This zinc-induced inhibition of copper absorption could be the result of competition for a com mon, apically oriented transporter or the induction of metallo thionein in intestinal cells by zinc. Because this protein has a higher binding affinity for copper than for zinc, copper is retained within enterocytes and its absorption is reduced. The interaction could also be responsible for reducing copper absorption during consumption of zinc supplements. When zinc-to-copper ratios of 2:1, 5:1, and 15:1 were fed to humans, there were limited effects on copper absorption (August et al. Infants fed a formula containing low concentrations of iron absorbed more copper than infants consuming the same formula with a higher iron concentration (Haschke et al. Such an interaction has been reported to produce reduced copper status in infants (Lonnerdal and Hernell, 1994; Morais et al. Fructose Studies in rats demonstrated that diets very high in fructose were associated with increased severity of copper deficiency in rats (Fields et al.

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The manufacturers advise that treatment may be interrupted for up to 4 weeks if adverse effects are not tolerated allergy forecast dallas today generic nasonex nasal spray 18gm free shipping. These may refect mutations in Smo which confer drug resistance allergy symptoms pressure in head order nasonex nasal spray with mastercard, for example by decreased drug binding allergy forecast ontario nasonex nasal spray 18 gm visa. There is interest in using this drug as neoadjuvant therapy allergy symptoms heavy head purchase nasonex nasal spray without prescription, shrinking large primary tumours prior to complex reconstructive surgery allergy symptoms headache fatigue 18 gm nasonex nasal spray otc, but further studies are needed to investigate this role allergy symptoms runny nose buy 18 gm nasonex nasal spray. For males (including those with vasectomy) having sexual intercourse with females of childbearing potential, counselling should be given of the need for barrier contraception with spermicide throughout treatment and for at least 2 months after the last dose. Fertility preservation strategies should be discussed with individuals who may wish to have children after completing therapy. Vismodegib is excreted in semen and male patients must use a condom when having sex with a female of childbearing potential during treatment and for 2 months after the last dose. Smo inhibitors including vismodegib are potent teratogens, causing severe birth defects and embryofetal death. In reality, the majority of female recipients will be beyond an age of childbearing potential. The manufacturers advise that pregnancy must be avoided for 24 months after the fnal dose. Lactation Mothers must not breastfeed while taking vismodegib and for 24 months after the fnal dose. Children Animal studies indicate a potential risk of short stature and tooth deformities in infants and children and vismodegib should not be given to those under the age of 18 years. Elderly In clinical trials of vismodegib approximately 40% of patients have been over the age of 65 years and vismodegib did not differ in terms of safety or effcacy in this age group compared with younger patients. Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib. While most children tolerate systemic medication well, neonates are at special risk of adverse drug reactions due to their immature liver and renal function. Much prescribing in children is off-label, as the pharmaceutical companies do not usually have suffcient data at the time marketing authorisation is granted. There is little incentive to do so unless the drug is principally for use in children. Off-label prescribing in children, should as far as possible be supported by evidence of safety and effcacy. The use of the product outside the terms of its license should be discussed with the child and their parents. Examples include the use of ciclosporin in childhood psoriasis and azathioprine in atopic eczema. Such treatment will usually be initialed and maintained in secondary or tertiary care. Some fexibility should be allowed in children to avoid waking them during the night so their night time dose may be given at their bedtime. Some drugs are only available in solid dosage which can pose administration problems for parents. It is important for parents to obtain the correct advice from the dispensing pharmacist on crushing the tablets or emptying the capsules into a suitable vehicle for administration. Liquid preparations can be available in different strengths so it is imperative when writing prescriptions to write clearly the drug dosage rather than the amount to be given. This should be discussed with the pharmacist and the parents and the same strength formulation dispensed each time to avoid over or under-dosage. A suspension may be formulated from capsule contents for neonates and infants but care must be taken that the suspension is dispensed in a dark bottle and not exposed to light. Alitretinoin (see Alitretinoin) Not recommended for use in children under the age of 18 years. Antibiotics commonly used for skin infections (see Antibiotics commonly used for skin infections) Indications: impetigo/infected atopic eczema (atopic dermatitis). Impetigo is common in young children and can be caused by Staphylococcus aureus and beta-haemolytic streptococci. These bacteria may also be implicated in infected fares of atopic eczema (atopic dermatitis). Flucloxacillin is the treatment of choice for staphylococcal infections, with erythromycin an alternative for penicillin-allergic children. Antifungals (see Antifungals) Oral azole antifungals (particularly itraconazole) and terbinafne are increasingly being used in preference to griseofulvin as they have a broader spectrum of activity and shorter treatment duration. Remember that immunocompromised children are at particular risk of fungal infections. Table 1 provides detailed information regarding age, formulation, appropriate dosages and licensing information. Oral therapy is usually required in order to eradicate the organism, alleviating disease symptoms quickly and safely and to reduce transmission to others. The choice of drug will vary according to the causative organism but as fungal culture may take up to 1 month it is reasonable to start therapy immediately. Griseofulvin is more effective against Microsporum species than Trichophyton species, and the latter may require prolonged therapy. The suspension is more palatable for children, but has become expensive and may be diffcult to source. Terbinafne has much higher effcacy against Trichophyton species than Microsporum species, and may be considered the treatment of choice for T. Itraconazole is active against both Microsporum and Trichophyton species and is widely used in many European countries. Fluconazole is licensed for use in the treatment of candidiasis in children of all ages and exists in an orange favoured liquid formulation. The antifungal medications and dosage regimens suggested for use in children are outlined in Table 2. Griseofulvin is no longer recommended for paediatric onychomycosis due to long treatment duration and lack of effcacy. Daily terbinafne and daily or pulsed itraconazole have been shown to be well-tolerated in paediatric populations, with faster response and higher cure rates than in adults due to the faster growth of the nail plate in children. Pityriasis versicolor may affect older children and usually responds to topical therapy. Fluconazole is licensed for use in mucosal and invasive Candida infection in children of all ages. Antihistamines (see Antihistamines) Indications: urticaria, pruritus in atopic eczema, allergic rhinitis. It is often associated with systemic symptoms and should be treated with oral antiviral medication. Biologics (see Tumour Necrosis Factor Antagonists) the only biologic currently licensed for severe plaque psoriasis in children (aged 6 years and older) is etanercept. Corticosteroids (see Corticosteroids) Prednisolone has predominantly glucocorticoid activity and is the corticosteroid most commonly used orally in children with severe atopic dermatitis. This suppression is greatest and most prolonged when the drugs are given at night and least when given in a single dose in the morning. Normal growth is allowed by 5 mg prednisolone/d for a child with 1 m2 surface area. Prolonged courses increase susceptibility to infections and severity of infections. Isotretinoin (see Isotretinoin) Although unlicensed in children under 12 years old, isotretinoin has been safely used in infantile acne and in younger children. The author recommends mixing with a fatty food such as peanut butter on toast in the dark! Severe infantile acne should be managed by those with special expertise in paediatric dermatology. If exposed to chickenpox, advice should be sought from the local microbiology department regarding post-exposure treatment. If confrmed to have chickenpox infection or shingles the child will need urgent specialist care and treatment. Immunizations with live vaccines such as polio and rubella should be avoided while children are taking systemic immunosuppressive drugs as the immunizations may not be effective. Most immunosuppressive agents are not licensed for use in the treatment of skin disease in children including ciclosporin (not licensed under 16 years), methotrexate and mycophenolate mofetil. Special point: vitamin D supplementation Children may have asymptomatic vitamin D defciency. Furthermore, studies have suggested that there may be an inverse relationship between the severity of atopic dermatitis and vitamin D levels, with vitamin D supplementation leading to a decrease in severity of disease. Therefore, in children with diffcult and severe eczema nutritional intake of vitamin D should be discussed with the parents and levels checked if appropriate. Simple nutritional vitamin D defciency can be prevented by oral supplementation with ergocalciferol (calciferol, vitamin D2) or colecalciferol (vitamin D3) daily, using multivitamin drops or preparations of vitamin A and D. With acknowledgements to Chin Gan and David Atherton, authors of this chapter in the 1st edition. Off-label and unlicensed drug prescribing in three paediatric wards in Finland and review of the international literature. Any abnormality requires further investigation to assess the underlying cause and the extent of liver damage (fbrosis). This will allow an informed decision to be made regarding the safety of a particular drug. Causes include excessive alcohol consumption, cholestasis (intra or extrahepatic) and medication. Bilirubin is conjugated with glucuronic acid in the liver and excreted in the bile. Rises in unconjugated bilirubin are derived from extrahepatic erythrocyte breakdown, i. A rise in conjugated bilirubin indicates hepatic disease and can be due to hepatocyte damage, cholestasis or synthetic liver failure. It allows identifcation of parenchymal disease, biliary obstruction, portal hypertension, vascular pathology and liver lesions. If abnormalities of liver function are detected, specialist advice from a hepatologist is essential prior to commencing a potentially hepatotoxic drug to ensure the appropriate choice and dose of drug and adequate monitoring. Liver dysfunction can occur any time between 1 week and 2 months after commencing therapy and up to 6 weeks after stopping. These are associated with loss of smaller bile ducts and peri-portal infammation which may progress to biliary cirrhosis and liver failure. Tetracyclines may also be hepatotoxic, causing jaundice and acute fatty infltration. In both forms hypersensitivity features may be present with rash, fever and eosinophilia. The liver injury is usually self-limiting with prompt drug discontinuation, but if treatment is continued inadvertently, progressive liver fbrosis and cirrhosis may develop. Sulphonamides have been known to produce liver damage since their development as antimicrobial agents. Hepatocellular injury with marked increases in transaminases is often accompanied by hypersensitivity features (rash and eosinophilia). Antifungals (see Antifungals) Ketoconazole: this is the most hepatotoxic oral azole antifungal drug, due to its extensive metabolism within the liver. Mild asymptomatic and transient elevations (<2 times upper limit of normal) of transaminases have been estimated to occur in up to 20% of patients, with clinically apparent hepatotoxicity incidence in approximately 1 in 2000 and 1 in 15, 000 users.

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Principle Radioimmunoassay continues to maintain a favoured position among microanalytical procedures not only because of its sensitivity allergy testing negative purchase nasonex nasal spray now, acceptable precision allergy symptoms in dogs eyes nasonex nasal spray 18 gm lowest price, robustness (working best in non-optimal conditions) and wide appli cability allergy testing nj buy nasonex nasal spray 18 gm mastercard, but also because it is comparatively the least expensive of numerous methods available for the detection and measurement of substances of clinical diagnostic interest allergy medicine beginning with l cheap 18 gm nasonex nasal spray with visa. It is amenable to bulk reagent based methodology allergy symptoms on skin order nasonex nasal spray 18gm overnight delivery, using at least some locally produced reagents allergy usf buy nasonex nasal spray american express, in contrast to methods totally dependent on black box type commercial kits. It has been computed that, while the dose from a single transatlantic flight equals 0. Academic personnel who will serve as laboratory managers need to be trained to a higher level, preferably postgraduate, than laboratory technicians, additionally learning interpretative skills according to their study approach (technical, scientific and/ or medical). It should be borne in mind that technicians using bulk reagents for in-house assays need a more thorough training than those who are merely using protocols provided with commercial kits. Similarly, greater use is being made of solid phase separation methods, particularly of those not requiring centrifugation, despite a possible slight increase in cost. In these and similar areas where a range of alternative approaches is available, the technical and economic advantages and disadvantages of each should be considered so that the workers concerned may arrive at informed decisions as to the most suitable approach for their particular situation. Academics and technicians would all require training in these areas, although academics would require more in-depth knowledge of, for example, the theoretical and mathematical concepts involved in designing an assay to suit a particular need. Laboratories in countries with high socioeconomic strength should place additional emphasis on cost effective overall laboratory management, critical evaluation of reagent supplies and on making the methodology more friendly to the user. Training should, however, also include the accepted standard operation procedures that manufacturers are expected to carry out before the batch release of the reagents. Training should include standard methods of assay validation (cross-reactivity, recovery and parallelism) and the means by which all essential features of an assay such as precision, bias, working range or sensitivity are ascertained before it is made available for clinical or research use. Workers should also be made aware that these characteristics cannot be fully determined and that they may change with fresh batches of reagents or other changes in assay conditions. In this context, knowledge of the stability and storage conditions to which different reagents may be subjected, such as stock and working solutions of standards and antisera, buffers and protein binding inhibitors, is necessary for preventing possible later problems. They should understand the concepts of within and between batch variability, the construction of quality control charts and curves, and of imprecision profiles and how these are used, in order to decide upon statistical acceptance or rejection of an assay result (or an entire assay on the basis of pre-set standards of precision and bias). The main causes of poor precision or unacceptable bias, especially when these are seen to occur in an assay that had previously been performing well, need to be understood so that remedial action can be taken at an early stage. Radioimmunoassay workers should be trained to use a suitable data processing package in their day-to-day work. A laboratory attached to a small hospital may provide only a clinical service confined to analytes of common clinical importance, such as thyroid related hormones, and find it most practical and economical to meet all of its reagent requirements from outside sources, whether abroad or local. Other centres that provide an expanded service may choose to produce at least some of the required primary reagents. These may range from the simplest, such as standards and quality control material for simple analytes of unique molecular structures for the commonest assays such as thyroid hormones and cortisol, to more sophisticated materials such as solid phases, tracers and antisera. Consequently, appropriate training in reagent production techniques should correspond to the type of laboratory the workers concerned are employed in. It would, however, be economically wasteful for a small centre with a workload of a few hundred samples per month to produce its own 125I tracer using imported 125I. In general, the larger the centre and the wider the scope of activity, the more worthwhile it is to train staff to produce their own working reagents. If a centre carrying out screening programmes for neonatal hypothyroidism or hepatitis B infection, for example, were to make its own solid phases from coating antibody solutions or labelling monoclonal antibodies, both obtainable in bulk form, costs would be reduced by a factor of 40. They would also benefit from instruction in good manufacturing practice and the procedures of sending out packages of reagents to other users, within and eventually outside the country. The end user should be aware of the logistic difficulties of customs clearance and prompt the appropriate local authorities to avoid delays in delivery. Mechanisms of training There are a number of possible paths for training in the above areas. A course of individual instruction at a laboratory with adequate facilities and staff is the best approach, with academics trained to a higher level, preferably postgraduate, wherever possible. Participants are expected to disseminate the expertise and skills they acquire within their home countries, most commonly by means of follow-up national training courses under the aegis of local atomic energy authorities or commissions. Since courses are usually of no more than two weeks duration, a progressive series of courses should be planned in order to cover all topics. The first course could include lectures on the basic physics of radionuclides, safe handling of radioisotopes, recent advances in immunoassay, separation methods, quality control and approaches to data processing. The second course could include lectures on standards and standardization, assay design and optimization, the evaluation of antisera including Scatchard analysis, iodination techniques, stability and storage of reagents, and techniques for the local preparation of simple reagents, such as standards and quality control material for selected analytes. This could also be demonstrated in practical classes and experiments carried out to validate locally produced reagents. Other practical classes could be designed to demonstrate and compare different separation methods. The second week sees a repetition of the first week, with the difference that the work is not done manually, but using a computer and a data processing software package or packages. Advanced reagent production A further group training activity may now be organized on advanced reagent production methods, confined to participants from centres equipped, or likely to become equipped, to undertake this activity to a significant extent. Not many laboratories, especially in developing countries, have the equipment and other facilities required for the production of monoclonal antibodies. If training in this area is required, it would be better provided on an individual basis at a suitable advanced centre. Participants in an external quality assurance scheme organized at the national or regional level 64 2. A training course devoted to tumour marker assays would focus on the special problems involved (high dose hook, etc. Such missions are both popular and effective because the same expert can train many persons and training is in a local context, taking into account circumstances in the host laboratory. An expert mission also has the advantage of establishing a relationship between a centre in a developing country, which may be working in relative isolation, and the more advanced home laboratory of the expert. Participants have an opportunity to update their knowledge and acquaint themselves with recent advances. The most appropriate and cost effective option for the training of technicians in developing countries is a suitable training centre within the region. In special fields, such as steroid receptor assays for example, an expert mission followed by a short period at an advanced centre outside the region may be necessary. Academics who need to be trained for longer periods and to a higher level may need to be accommo dated at advanced centres in developed countries. Specially identified labora tories may be developed to become a centre of excellence for training purposes within a given country or region. Ideally, nurses should serve in diagnostic nuclear medicine sections and be present during nuclear cardiology stress testing. A nurse is the first interface with the ward nursing of inpatients and should be able to inject ward patients with radiopharmaceuticals. In order to carry out these functions correctly, nurses need a basic knowledge of radiation, radionuclides and the biological effects of radiation, and should receive training on the safe handling of radioactive materials as well as radiation protection. Education and training should be offered both in undergraduate courses in a school of nursing and in postgraduate training courses in hospitals. Nurses should receive a final briefing before they start working in a department of nuclear medicine. In developing countries, nuclear medicine has historically often been an offshoot of pathology, radiology or radiotherapy services. The level of nuclear medicine services is categorized according to three levels of need: Level 1: this level is appropriate where only one gamma camera is needed for imaging purposes. The radiopharmaceutical supply, physics and radiation protection services are contracted outside the centre. A single imaging room connected to a shared reporting room should be sufficient, with a staff of one nuclear medicine physician and one technologist, with backup. Level 2: this level is appropriate for a general hospital where there are multiple imaging rooms in which in vitro and other non-imaging studies would generally be performed as well as radionuclide therapy. Level 3: this level is appropriate for an academic institution where there is a need for a comprehensive clinical nuclear medicine service, human resource development and research programmes. Introduction this section deals with the establishment of a nuclear medicine service for performing diagnostic and therapeutic procedures. Recommendations related to human resources development and the procurement of equipment, specifi cations of imaging devices and clinical protocols are expanded on in other sections. The first step in establishing a nuclear medicine service is to consider the space, equipment and staffing requirements. Space requirements will vary according to the level of the service, depending on whether a simple in vitro or in vivo imaging laboratory is envisaged or whether there are plans for a full in vitro laboratory and for in vivo imaging therapeutic procedures. The initial design and planning should take into account a number of factors in addition to the space needed for routine imaging and staffing needs. Radioactive waste disposal must follow local radiation protection guidelines and space must be available for waste storage. Nuclear medicine is an advanced but cost effective specialty which can solve specific clinical problems. Since it changes rapidly with the development of new technologies for imaging devices and new radiopharmaceuticals, it calls for specialized training together with specific site preparation. Nuclear medicine staff need to have sufficient administrative skills to interact with referring physicians, hospital administrators and financial supporting bodies such as 68 3. The general public needs to be both reassured and informed (about treatment), as proper interaction with patients requires their full cooperation. The level of services, information and patient interaction varies according to region, general standard of educational and socioeconomic conditions, and the standard of health care. Nuclear medicine services vary from one country to another, although cardiology and nuclear oncology are generally the most commonly performed studies. The planning of a nuclear medicine department should be preceded by a study of population demographics and the prevalence of diseases in the respective country. This groundwork allows for prioritization and planning of an appropriate nuclear medicine service. Since nuclear medicine serves both inpatients and outpatients the location of the site should give easy access to both groups. This isolates nuclear medicine from the referring physicians, reduces interaction between medical staff and, furthermore, creates unnecessary fear among the public. Nuclear medicine services can range from basic in some countries to advanced in others. Once the level of service has been defined, personnel training should take place before the site is prepared or equipment procured. Similarly, each country should have regulatory agencies to set the rules for licensing, radiation protection, radiation safety and radioactive waste disposal. In some countries it is advisable to set up a planning board to supervise human resource development, oversee current services and plan future development. The planning board can also recommend guidelines to ensure continuous quality control and education. Equipment While the capacity and quantity of individual pieces of equipment needed depend on the volume of the service, minimum requirements are as follows: (a) A collimated scintillation probe and counting system for uptake measure ments of thyroid function and other in vitro and diagnostic studies. It is important that the environment in the hospital and the nuclear medicine department is suitable for the equipment as described below: (a) A stable uninterrupted power supply is vital and it has to be secure. Prior to installation of the gamma camera and electronic instruments, and during their service lives, the equipment needs to be protected from disturbances, such as power outages, voltage fluctuations and frequency fluctuations, in the mains power supply. Staff the number of staff will depend on the volume of both in vitro and in vivo work. A larger area provides a more pleasant working environment and reduces the risk of radiation to staff. In some countries, rooms should have double glazed and insulated windows to avoid the buildup of dust. Tight fitting oversize doors and efficient heating, air-conditioning and humidity control units are also required. All rooms should have their own separate power supply and stabilizers and be equipped with hand washbasins with hot and cold running water. Cardiac stress laboratory for nuclear cardiology the cardiac stress laboratory should be planned in consultation with the cardiologists and equipped for treadmills and bicycles or pharmacological stress studies. Conference room the conference room can be used primarily for interdepartmental confer ences, consultations with physicians and support activities for nuclear medicine staff. While functions could be accommodated in one large room with or without a partition, two separate rooms might be preferable. A library, Internet access and other teaching aids should be available to the conference room(s).

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