Dung Thi Le, M.D.

• Associate Professor of Oncology

https://www.hopkinsmedicine.org/profiles/results/directory/profile/0016139/dung-le

Water lines all receptor sites symptoms 8 days before period purchase duphalac with a mastercard, and an incoming drug must either incorporate the water into the receptor binding process or displace it medications 230 duphalac 100ml low price. Amino acids medicine vs dentistry duphalac 100ml on-line, as implied by their name medicine guide 100 ml duphalac otc, are difunctional molecules: they possess a basic amino group and an acidic carboxyl group. Arising from this difunc tional structure, amino acids are said to be amphoteric, since they can react as either acids or bases. The most important amino acids, both structurally and functionally, are the amino acids, which have a single carbon atom (the carbon) separating the amino group from the carboxyl group. Proline is a secondary amine whose nitrogen and carbon atoms are part of a five-mem bered pyrrolidine ring. With the exception of glycine, the carbons of the amino acids are stereogenic centers of chirality. The side-chains of each amino acid then bristle away from this backbone structure. Chains with fewer than fifty amino acids are peptides, while those with more than fifty are proteins. Peptide and protein chains twist and turn upon themselves, producing elaborate and complex structures that enable bioactivity. Primary structure refers to the amino acid sequence of the protein; secondary structure (consisting of helices, sheets, and turns) describes how segments of the protein backbone orient into regular patterns via intramolecular hydrogen bonding along the backbone; tertiary structure describes how the entire protein molecule coils into a three-dimensional shape by means of multiple intramolecular interactions involving both backbone and side-chain atoms; quaternary structure refers to the process whereby many individual protein molecules come together, through various intermolecular interactions, to form a larger aggregate structure. Functional proteins are typically globular proteins (soluble, compactly coiled, roughly spherical in shape) and include hemoglobin (involved in oxygen transport), immunoglobulins (involved in immune responses), and insulin (involved in glucose metabolism). Catalytic proteins, also called enzymes, function by bringing reactant molecules together, positioning them in a favorable orientation for reactivity, and furnishing any required acidic or basic sites. For purposes of drug design, these enzymes may be grouped into six main classes, according to the reaction that they catalyze; in turn, within each group, there are a variety of different enzymes: 1. Hydrolases Amidases Caspases Esterases Glycosidases Lipases Nucleases Exonucleases Endonucleases Peptidases Proteases 2. Oxidoreductases Catalases Dehydrogenases Oxidases Oxygenases Peroxidases Reductases 6. Since enzymes are key catalysts in many metabolic processes, they have traditionally been (and will continue to be) among the most important targets for drug design. These nucleic acids are biopolymers, composed of monomeric building units called nucleotides (figure 8. Just as proteins can be hydrolyzed to amino acids and poly saccharides can be hydrolyzed to monosaccharides, nucleic acids can be hydrolyzed to nucleotides. Subsequent com plete hydrolysis of a nucleotide furnishes three structural subunits: 1. A phosphate ion A structural variant of a nucleotide is a nucleoside, which is a nucleotide with the phos phate group removed. These heterocyclic bases are attached through an N-glycosidic linkage to C1of the ribose or deoxyribose. The phosphate group is pre sent as a phosphate ester and is attached at either the C5or C3position. Through these various linkages, the nucleotides are assembled to form the polymeric nucleic acid. When the two strands of the double helix coil, two types of groove are produced, a major groove 1. In drug design, such structural data is crucial in designing anti-tumor drugs for the treatment of cancer and in understanding the carcinogenic toxicity of flat, polycyclic aromatic molecules. Translation is the process by which the genetic messages are decoded and used to construct proteins. Nucleotides and nucleosides have emerged as important molecules in medicinal chemistry. In the 1950s, Elion and Hitchings discovered that 6-mercaptopurine had antitumor properties. This pioneering discovery opened the door for many subsequent studies of nucleotide derivatives as therapeutics. This definition defines lipids in terms of a physical property (solubility) and differs from structural definitions used for proteins or carbohydrates. Not surprisingly, lipids are highly varied in their structure; from the medicinal chemistry perspective, there are five classes of lipids: 1. Steroids Each of these classes has some relevance to medicinal chemistry and drug design. Waxes are mixtures of esters of long-chain carboxylic acids with long-chain alcohols. Hydrolysis of a fat or oil in an aqueous alkaline solution (saponification) produces glycerol and three fatty acids. Polyunsaturated fatty acids, such as linoleic or linolenic acid, contain more than one double bond; saturated fatty acids contain no double bonds. The primary bio logical function of triacylglycerols in animals is to function as an energy storage depot; when triacylglycerols are metabolized they yield more than twice as many calories as does an equal mass of a protein or carbohydrate. Lipid biochemistry will receive increasing attention in medicinal chemistry because of the epidemic of obesity occurring in developed countries with its associated co-morbidities such as diabetes and accelerated atherosclerosis, leading to strokes and heart attacks. There is compelling evidence that too much saturated fat in the diet can lead to the development of heart disease, and perhaps cancer as well. Moreover, there is also accu mulating evidence that trans fats can likewise lead to an increased risk of cardiovascular disease. Polyunsaturated oils tend to react by auto-oxidation, causing them to become rancid and have a short shelf life; accordingly, partial hydrogenation is performed to convert the oil into an appealing semi-solid with a prolonged shelf life. Regrettably, a problem with partial hydrogenation is that the catalyst isomerizes some of the unreacted double bonds from the natural cis configuration to the unnatural trans configuration. Phosphoglycerides, organized into a lipid bilayer, comprise the major lipid component of cell membranes. Since this bilayer is the principal barrier to the pas sage of molecules into and out of a cell, phosphoglyceride structure is of interest in medicinal chemistry and drug design. Phosphoglycerides contain a glycerol backbone linked by ester bonds to two fatty acids and one phosphoric acid. Rather than a glycerol backbone, these lipids have sphingosine (a substituted dihydroxyamine) for their back bone structure. One particular sphingolipid, sphingomyelin, is a major lipid constituent of neuronal axons within the brain and nervous tissue. The sphingolipids, together with proteins and polysaccharides, constitute myelin, the lipid-based coating of neurons within the brain. Since the need to develop drugs for demyelinating diseases, such as multiple sclerosis, is a continuing drug design target, interest in sphingolipids is of relevance to medicinal chemistry. The 1982 Nobel Prize in medicine was awarded to Bergstrom, Samuelson, and Vane for their pioneering work in prostaglandin chemistry. Prostaglandins affect blood pressure, blood clotting, gastric secretion, kidney function, inflammation, and uterine contractility. In nature, prostaglandins are biosynthesized from arachidonic acid, a C20 unsaturated fatty acid. In addition, prostaglandin-like molecules, including the leukotrienes, thromboxanes, and prostacyclin, are also important drug design targets for inflammatory disorders such as asthma. The 1939 Nobel Prize in chemistry was awarded to Leopold Ruzicka for his pioneering work on the chemistry of terpenes, agents that have been used as therapeutics since antiquity. By steam distilling various plant materials, mixtures of odoriferous compounds, known as essential oils, were obtained; terpenes are the most important constituents of these oils. Although they exhibit tremen dous diversity, all terpenes are structurally related according to the isoprene rule of Ruzicka. They arise from a head-to-tail joining of 5-carbon isoprene (2-methyl-1,3 butadiene) units; carbon-1 is the head, carbon-4 is the tail. Terpenes are then classified by the number of constituent isoprene units: monoterpenes are 10-carbon compounds biosynthesized from two isoprene units; sesquiterpenes are 15-carbon molecules from three isoprene units. Camphor and carvone (spearmint oil) have been used as soothing agents in the past history of pharmaceutical compounds. More recently, the role of terpenes in bio chemistry has been more fully appreciated.

To escape death from kidney disease we must avoid being flooded with urease and nickel 8h9 treatment cheap duphalac 100 ml with mastercard. To escape all these disease types we must avoid parasitism or keep our youth with its magical killing power medications you can take when pregnant buy duphalac from india. What was once our sustenance treatment resistant anxiety purchase duphalac on line, our precious trace minerals treatment whiplash cheap generic duphalac uk, has been marshaled by our enemies and oxidized to useless trash that must be cleared. As long as the body can continue to kill generation after generation of invading parasites and their beneficiaries, the fungi and yeast, no one toxic element becomes overwhelming. But when this evolution is stalled by super-imposed metals from our environment or from inability to kill them (loss of immune power) death comes from disease, not old age. It appears to come in waves, building to a crest and then receding, in fairly brief bursts, especially in fall and spring. This may be due to testing with an inexpensive frequency generator (Tenma model 72-380) that was only accurate to 100 Hz. It might also be due to using more voltage (2-3v) than necessary (like when a powerful radio station comes in at its own frequencies and ones nearby, too). If the same person retests the same specimens with the same equipment within a few days, the results will be absolutely identical (within 1 Hz) 90% of the time. When organisms are dead, killed in your body by some means, there is no resonance left that your Syncrometer can detect. My tentative answer is that slides were prepared after fixing the pathogens carefully to retain details of structure that continue to have capacitance. Perhaps this would not happen if they were killed naturally so their proteins were quickly denatured. Bandwidth Of Organism Families In general, the smaller the organism the lower the frequency and narrower the bandwidth. The original frequency, 277, was selected from a range whose values have been lost. Tapeworms can have very large bandwidths (range of frequencies), and it varies by the length of the specimen! Finding out the frequencies of these illnesses helps you identify them (use the Pathogen Frequency Chart) and also lets you know if you are getting them back chronically. I have no financial interest in, or influence on, any of the companies listed in this chapter, except for having relatives in the Self Health Resource Center. Transitional epithelium 169 Testing Laboratories these labs are willing to test food and consumer products for pollutants. Completely fill containers to eliminate headspace (the air trapped in the bottle). Keep in mind that your purpose is to improve your own health by switching to cleaner drinking water. Tips for sample collection: a) Use a new bottle, rinsed with the same water you are testing. I stress benzene pollution because recovering your health is not possible if your drinking water contains one, or even 0. Many labs test only for levels at the Reporting Limit, because their clientele consists of public water utilities whose main purpose is to remain in compliance and keep costs low. Sealed and otherwise wrapped items may be submitted unopened to a laboratory for analysis. If only Benzene, toluene and xylene are requested, fees may be around $90 per sample. Water and water-soluble compounds may be easier to analyze than oily foods (which require a preceding concentration step). The labs listed above were cooperative in discussing our special need for very low detection levels. Metals used for filling teeth, such as mercury amalgam, are difficult to analyze for polluting metals, because separation of similar compounds is difficult. Thus finding traces of a toxic metal pollutant in a filling is not possible at this time. This simple bit of technology grew into architecture when geometry and trigonometry were added. This bit of technology grew into the industry of electricity with all of its subdivisions like power, electronics and communications. With it you can approach any human being or animal and soon know what is present and what is happening at different locations, be it tiny, as in a brown fleck on your skin or large as your leg bone. We can expect that as the technology grows many people will get involved, not just some ivory tower researchers. But, hopefully, you will find this new technology as exciting, even more so, as the other arts and sciences. If you can hear the difference between notes on a musical scale and have perseverance to learn the new skill you can easily master this new technology. The real scientist actually pursues a truth and expresses her/his curiosity to see, to hear, to measure, to watch how things happen. There is always the suspense of finding the answer to a riddle with just weak clues around you. Many new sciences got their start at the grassroots level, not through academic training. Creativity can charm us again, this time as Popular Health (see the fictitious example). Remember to observe the elementary rules and reflections for both young and old scientists, both academically trained and less academically trained: 1. Never make explanations that are dead ends so there can be no further experimentation. This idea must be something that allows you to experiment further, not a dead end. And finally, long before it is absolutely proven, and long before you are yourself convinced of its correctness you share your observations and views. Clark has a Bachelor 1 (800) 519 of Arts, Magna Cum Laude, and the Master of Arts with High 2465 Honors from the University of Saskatchewan, Canada. Then she studied for two years at McGill University before attending 1 (619) 476 the University of Minnesota and obtaining her Doctorate degree 7400 in cell physiology in 1958. After doing government sponsored research for almost ten years at Indiana University, she began private consulting in nutrition in 1979. She continued her studies to earn a Naturopathy Degree and an amateur radio license. The freedom to pose her own questions and pursue her own ideas led to the breakthrough discoveries described in this book. Huther 158 18 *Composite muscle (Wards) *Composite muscle (Wards) 159 21 folicle mite follicle mite 161 last-2 E. The peak age rounding structures (meningioma, dermoid, epider at onset lies within the second and third decades of moid). Normally, germinal cells not residing teratomas that are slow growing and noninvasive are in tissues destined to form sex organs become apop the least common variant (5%). The pure germi totic and die; presumably some may occasionally sur nomas are more commonly found in the pineal re vive and over many years transform into a neoplasm. Summary of Pathology in 154 Patients Undergoing Surgery for Pineal Region Tumors at the New York Neurological Institute Mean Age Tumor Pathology No. Germinomas are with intracranial germ cell tumors is very dependent typically composed of two cell types: large, uniform on histology, it is imperative to establish an unequiv polyhedral cells with clear cytoplasm that resemble ocal diagnosis prior to the administration of radio primordial germ cells; and smaller lymphoid cells. This tumor is consid ered to represent a neoplasm whose cells are par tially differentiated into extra-embryonic structures that express yolk sac potential (Gonzalez-Crussi, 1979). Embryonal cell carcinoma is considered the most histogenetically primitive of the germ cell tu mors, with features of anaplastic columnar to cuboidal cells arranged in sheets and cords (Bjorns son et al. This tumor shows a variable pat tern of acinar, papillary tubular, or solid structures. Hematoxylin and eosin, carcinoma may give rise to a multiplicity of tumor ad 200.

In Step A medications ok for pregnancy trusted 100 ml duphalac, the smallest bioactive fragment of the larger peptide is identified; in Step B treatment 3rd degree av block 100ml duphalac, a process such as an alanine scan is used to identify which of the amino acids are impor tant for bioactivity; in Step C medicine wheel images generic 100ml duphalac with mastercard, individual amino acids have their configuration changed from the naturally occurring L-configuration to the unnatural D-configuration (in an attempt to make the peptide less naturally peptidic); in Step D medications pancreatitis generic duphalac 100 ml, individual amino acids are replaced with atypical unnatural amino acids and amino acid mimics; in Step E the peptide is cyclized to constrain it con formationally; finally, in Step F, fragments of the cyclic peptide are replaced with bioisosteres in an attempt to make a non-peptidic organic molecule. Next, this segment is then rebuilt isosteric fragment by isosteric fragment, gradually replacing each portion of the molecule in a stepwise fashion. For example, the amide bond may be replaced by a bioisosterically equivalent amide bioisostere. In this fashion, an equivalent but non peptidic organic molecule drug eventually emerges. An alternative approach is a little less plodding and perhaps a little more elegant. Next, an educated guess (hopefully based on some exper imental data) is made to suggest which portion of the peptide is the pharmacophore. For example, these data may show that the peptide pharmacophore contains a carboxylate group located 4. Using these precise data, databases of known organic molecules are then computation ally searched to identify an organic molecule with similar functional groups held in the same position in three-dimensional space. These include nucleic acids, lipids, and carbohydrates, which are discussed in detail in chapter 8. Likewise, there is a need to develop small organic molecules as mimetics of these other endogenous molecules. Although not as clearly defined as peptidomimetic chemistry, ultimately, nucleotidomimetic or carbohydromimetic chemistries may eventually emerge as new design strategies for lead compound identification. An alternative is to exploit molecules that are endogenous to other life forms (animal or plant) but do not naturally occur within humans. Such molecules would be classed as exogenous from the perspective of drug design for humans. Digitalis for congestive heart failure was first isolated from the foxglove plant. Various antibiotics (penicillin) and anticancer agents (taxol) are derived from natural product sources. There is good reason to be optimistic about the potential future usefulness of such exogenous compounds as a continuing source of potential lead compounds. With many thousands of years of trial-and-error by evolution on her side, Mother Nature is a vastly superior experimentalist to any mere human organic chemist. Amphibian evolution has enabled the biosynthesis of antibacterial peptides on the skins of frogs so that they can avoid infections as they swim through stagnant swamp waters; peptides such as these could be a good starting point for the peptidomimetic design of novel antibacterial agents. Reptile evolution has culminated in the biosynthesis of neuroactive venoms for pur poses of hunting and defense; these molecules have been fine-tuned by evolution as agents specific for neurotransmitter receptors. Plant evolution has culminated in a wide variety of biomolecules that affect any animal that may choose to eat them: it is bio logically advantageous for some plants to be eaten so that their seeds can be dispersed in the stool of the animal that ate them; conversely, it is biologically advantageous for other plants to produce noxious chemicals to decrease the likelihood of their being eaten. Because of these diverse biological activities, any of these non-human biosyn thetic molecules could, in principle, be a lead compound for human drug discovery. Another promising feature of animal or plant-based natural products is that they are a superb source of molecular diversity. As a synthetic chemist, Nature is much more creative and is not constrained to the same finite number of synthetic reactions typically employed by human synthetic organic chemists. Furthermore, when developing compound libraries for high throughput screening (see section 3. Although ethnopharmacology, the scientific investigation of natural products, folk medicine, and traditional remedies, has led to some bona fide drugs. However, natural products have always been and still are an inexhaustible source of drug leads as well as drugs. From each of these sources, extracts conducted with solvents with different polar ities will yield different natural products. This complex extraction system ensures the identifica tion of all possible candidate molecules from a plant source. Several research institutes and well-established groups (notably the Scripps Institute of Oceanography and the University of Hawaii) are producing some very promis ing results in this field. The isolation of prostaglandins from a coral was one of the more startling recent discoveries in marine pharmacology. An extension of natural products chemistry is the biochemical information derived from the study of metabolic pathways, enzyme mechanisms, and cell physiological phenomena; this research has revealed exploitable differences between host and para site (including malignant cells), and between normal and pathological function in terms of these parameters. The large and fertile area of antimetabolite (metabolic inhibitors) and parametabolite (metabolic substitutes) chemistry is based on such stratagems, and has found use in the field of enzyme inhibition and in conjunction with nucleic acid metabolism. The design of drugs based on biochemical leads remains a highly sophis ticated endeavor, light-years removed from the random screening of sulfonamide dyes in which it has its origin. However, of the approximately 10200 small organic molecules that could theoretically exist in our world (1052 of which are drug like molecules), many would be purely synthetic substances that do not occur naturally. The concept of rational drug design (in contrast to its logical counterpart, irrational drug design) implies that the disease under consideration is understood at some funda mental molecular level and that this understanding can be exploited for purposes of drug design. Such an understanding would facilitate the design of purely synthetic mol ecules as putative drugs. Although this ideal of rational drug design has been pursued for many years (see section 3. Recognizing its chemical similarity to iodine, French physicians immediately exploited it as an iodine alternative for the treat ment of numerous conditions, including syphilis and thyroid goitre. Although no bene ficial effects were reported for either bromine or its potassium salt, their widespread use persisted and eventually the depressant effect of potassium bromide on the nervous system, so-called ivresse bromurique, was recognized. In 1857, Sir Charles Locock, the physician accoucheur to Queen Victoria, ascrib ing to the then prevalent view that epilepsy arose from excessive sexuality, introduced bromide as an anaphrodisiac to suppress the supposed hypersexuality of epileptics. Although side effects had been considerable (and included psychoses and serious skin rashes), bromides were successful in 13 of the 14 patients treated. On 11 May 1857, at a meeting of the Royal Medical and Chirurgical Society, Locock proudly reported his success in treating hypersexual epilepsies with bromides. He argued that logical and rational drug development had finally been achieved for the time: epilepsy arises from excessive sexuality; potassium bromide suppresses sexual ity; therefore, potassium bromide successfully treats epilepsy. In reality, it was little more than yet another serendipitous discovery, since hypersexuality has absolutely nothing to do with epilepsy. Regardless of the flawed reasoning, bromides were a major step forward in the treatment of epilepsy and their use persisted until the introduction of phenobarbital in 1912. Rational drug design is an iterative process, dependent upon feedback loops and new information. When the drug designer makes the first prototype molecule, this molecule becomes a probe with which to test the drug design hypotheses. The molecule can then be further designed and refined to better improve its ability to dock with the receptor site and elicit a biological response. The successful ratio nal design of a drug is similar to solving a major puzzle using your wits and wisdom. The macromolecules involved in the disease have been determined; the structures of these macromolecules have been ascertained using X-ray crystallography and/or computer-aided molecular design; a small organic molecule capable of binding to the macromolecule has been cleverly designed; a synthesis for this small organic molecule has been devised; and biological testing has confirmed the bioactivity of the small organic molecule. Despite protestations from the naysayers who despondently claim that all drugs are discovered by serendipity, there is an increasing number of examples that exemplify the successes and practical utility of rational drug design. Perhaps one of the earliest exam ples is the discovery of cimetidine, an H2-antagonist drug used for the treatment of peptic ulcer disease. These structural studies greatly facilitated the process of rational drug design, ultimately leading to six rationally designed therapeutics: amprenavir, indinavir, nelfinavir, ritonavir, saquinavir, and lopinavir. As evidenced by the aforementioned examples, structural chemistry is front and center in enabling rational drug design.

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Metaphase spreads are selected medications you can crush purchase duphalac 100ml with mastercard, and the chromosomes are arranged in descending order by size and compared with a standard medications like gabapentin buy generic duphalac 100 ml. Techniques constantly improve in terms of the types of staining available medicine shoppe discount 100 ml duphalac otc, and the analysis is now often computerized medications gabapentin purchase duphalac no prescription. This often makes it worth repeating the test if it has not been done for some years. Comparative genome hybridization this technique is becoming increasingly available and may replace routine karyotyping in the near future. Effectively ahigh resolution karyotypeit detects copy number imbalances (due to deletion or duplication) relative to a control sample. Balanced rearrangements, inversions or other rearrangements that do not alter total copy number will not be detected. Ring chromosome 20 mosaicism this is a recognized syndrome of severe epilepsy and learning difficulties with severe behavioural features. Ring chromosome 20 mosaicism should be speci ed if this is a consideration so that more cells are examined: examination of 50 cells will identify 6% mosaicism with 95% con dence. Stop and maintain the cuff for 1 min, then release the cuff, and take blood for lactate and ammonia at 2 and 12 min. Transferrin is a sensitive and convenient marker, secreted by the liver and normally present in different isoforms due to dif ferences in glycosylation. Biotinidase the phenotypic range of this treatable de ciency state is broad (see b p. Consider testing especially where there is hypotonia, severe infan tile epilepsy, alopecia, rashes, and hearing loss. Note: most speci c enzyme assays can be carried out on cultured skin broblasts, cultured amniotic uid cells or chorionic villus samples. Whilst not speci c, the diagnosis of a number of neurological conditions may be assisted by the demonstration at electron microscopy of inclusion bodies in apocrine sweat gland-containing skin. Establishment of broblast culture may be indicated for enzyme analysis to investigate inborn errors of metabolism or chromosome analysis to look for tissue speci c mosaicism. Skin for broblast culture must be scrupulously sterile or contaminants will prevent the culture establishing. Take a small sample (a few millimetres in diameter) to prevent necrosis of the centre of a larger sample. For broblast culture collection into tissue culture medium is strongly preferred (use saline only exceptionally). Avoid iodine containing compounds such as betadine as these interfere with cell growth in culture. Although the technique is relatively simple, success depends on obtaining several samples of adequate size from a single insertion site. Subsequent specimen processing should only be done by laboratory technicians familiar with the techniques. Intrathecal medicine Inadvertent intrathecal injection of cytotoxics intended for intravenous use in the treatment of acute lymphoblastic leukaemia has been a repeated cause of medical tragedy. Intrathecal cytotoxics should only be given by paediatric oncologists in a dedicated setting. Shunt tap this should ideally only be performed by a neurosurgeon as different shunt designs have different access points and some are not suitable for tapping (Figure 2. Neuropsychological testing complements and supplements assessment by an educational psychologist. Domains and modules Development is considered to bedomain speci cA domain is a set of representations sustaining a particular area of knowledge. Visuospatial Visuospatial tests assess right hemisphere function predominantly, although a left hemisphere in uence may be present if verbal mediation occurs. Visuomotor functioning Closely related to visual item perception and visuospatial processing, visuomotor functioning adds a manipulation or graphomotor component to the perceptual tasks. Social-emotional functions these are particularly important in children with non-verbal learning disabilities. Observation of spontaneous behaviour is also necessary to assess execu tive function, as thestructurednature of formal assessment compensates for the de cits being sought. Qualitative data (the types of errors pro duced) may be useful in determining context-related processing difficulties from executive function problems. This page intentionally left blank Chapter 3 103 Signs and symptoms Agitation and confusion 104 Back pain 106 Behaviour disorders 107 Developmental impairment 109 Exercise limitation and muscle pain 117 Eye movement abnormalities 119 Facial movement abnormalities 126 Facial sensation abnormalities 130 the oppy infant 132 Foot deformities 135 Funny turns: episodic events 136 Funny turns: likely epilepsy Acute management One of many important reasons for correctly distinguishing an acute con fusional state from emotional reaction is the very different approach to management. However attempts to argue, persuade, or cajole a child with an acute con fusional state will be counter-productive. For example, the child with genetically-determined learning difficulties under pressure at school adopting strategies for task avoidance or attention seeking. Speci c patterns Oppositional de ant disorder the child is often negative and de ant, with a frequent loss of temper; arguing or non-compliant with adults. The child may be angry and resentful, irritable and easily annoyed, and deliberately annoying other people. Conduct disorder the child shows a persistent tendency to transgress normally accepted rules or the rights of others. Attention de cit disorder A developmental disorder resulting in difficulty directing attention to tasks, listening to or following instructions, or organizing activities. Children exhibit distractibility, varying degrees of dgetiness and impulsivity. Treatment with stimulant drugs (methylphenidate, atomoxetine) may be indicated; a behavioural approach with rm, consistent handling with the de nition of boundaries of acceptable behaviour usually used rst, particularly for the under 5s.