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If alternate segregation occurs, the offspring will inherit either a nor ~,I mal chromosome complement or will be a normal carrier like the. Consequences of a Robertsonian Translocaton in One Parent (illustrated with a male), I " f Robertsonian Translocation and Down Syndrome. Approximately 5% of Down syndrome cases are the result of a Robertsonian translocation affecting chromosome 14 and chromo some 21. When a translocation carrier produces gametes, the translocation chromosome can, segregate with the normal 14 or with the normal 21. A diagram can be drawn to represent the six possible gametes that could be produced. The key difference is 47 versus 46 chromosomes in the individual with Note,, Down syndrome. The recurrence risk (determined empirically) for female translocation carriers is I carner: 10-15%, and that for male translocation carriers is 1-2%. The elevated recurrence risk for translocation carriers Adjacent segregation versus noncarri~rs underscores the importance of ordering a chromosom~ study when Down produces unbalanced syndrome is suspected in a newborn. Examples include: Prader-Willi syndrome Angelman syndrome If a micro deletion includes several contiguous genes, a variety of phenotypic outcomes may be part of the genetic syndrome. Inversions thatinclude the centromere are termed pericentric, paracentric) whereas those that do not include the centromere are termed paracentric. Pericentric Inversion of Chromosome 16 A male infant, the product of a full-term pregnancy, was born with hypospadias and ambiguo genitalia. His brother had two childre " " both healthy, and the father assumed that he would also have normal children. A Pericentric Inversion of Chromosome 3 l Ring Chromosome I 1: A ring chromosome can form when a deletion occurs on both tips of a chromosome and the r remaining chromosome ends fuse together. The karyotype of an isochromo some for the long arm of the X chromosome would be 46;X,i(Xq); this karyotype results in an individual with Turner syndrome, indicating that most of the critical genes responsible for the Turner phenotype are on Xp. Isochromosome Xq Uniparental Disomy Uniparental disomy is a rare condition in which both copies of a particular chromosome are contributed by one parent. This may cause problems if the chromosome contains an imprinted region or a mutation. For example, 25-30% of Prader Willi cases are caused by maternal uni parental disomy of chromosome 15. A smaller percentage of Angelman syndrome is caused by paternal uniparental disomy of chromosome 15. Spectral Karyotyping Spectral karyotyping involves the use of five different fluorescent probes that hybridize dif ferentially to different sets of chromosomes. In combination with special cameras and image processing software, this technique produces a karyotype in,which every chromosome is "painted" a different color. This allows the ready visualization of chromosome rearrangements, such as small translocations. A 26-year-old woman has produced two children with Down syndrome, and she has also had two miscarriages. A 6-year-old boy has a family history of mental retardation and has developmental delay " and some unusual facial features. Multiple attempts to have a second child have ended in miscarriages and spontaneous abortions. Karyotypes of the mother, the father, and the most recently aborted fetus are represented schematically below.

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However, their widespread availability has led to abuse of those opioids with euphoric properties. They have also been identified on the peripheral sensory nerve fibers and their terminals and on immune cells. Brainstem: Opioid receptors influence respiration, cough, nausea and vomiting, blood pressure, pupillary diameter, and control of stomach secretions. Medial thalamus: this area mediates deep pain that is poorly localized and emotionally influenced. Spinal cord: Receptors in the substantia gelatinosa are involved with the receipt and integration of incoming sensory information, leading to the attenuation of painful afferent stimuli. Limbic system: the greatest concentration of opiate receptors in the limbic system is located in the amygdala. These receptors probably do not exert analgesic action, but they may influence emotional behavior. Periphery: Opioids also bind to peripheral sensory nerve fibers and their terminals. The role of these receptors in nociception (response or sensitivity to painful stimuli) has not been determined. Codeine is present in crude opium in lower concentrations and is inherently less potent. Morphine also appears to inhibit the release of many excitatory transmitters from nerve terminals carrying nociceptive (painful) stimuli. Analgesia: Morphine causes analgesia (relief of pain without the loss of consciousness). Patients treated with morphine are still aware of the presence of pain, but the sensation is not unpleasant. However, when given to an individual free of pain, its effects may be unpleasant and may cause nausea and vomiting. The maximum analgesic efficacy and the addiction potential for representative agonists are shown in Figure 14. Respiration: Morphine causes respiratory depression by reduction of the sensitivity of respiratory center neurons to carbon dioxide. This occurs with ordinary doses of morphine and is accentuated as the dose increases until, ultimately, respiration ceases. Respiratory depression is the most common cause of death in acute opioid overdose. Depression of cough reflex: Both morphine and codeine have antitussive properties. In general, cough suppression does not correlate closely with analgesic and respiratory depressant properties of opioid drugs. The receptors involved in the antitussive action appear to be different from those involved in analgesia. Morphine excites the Edinger-Westphal nucleus of the oculomotor nerve, which causes enhanced parasympathetic stimulation to the eye (Figure 14. There is little tolerance to the effect, and all morphine abusers demonstrate pinpoint pupils. Emesis: Morphine directly stimulates the chemoreceptor trigger zone in the area postrema that causes vomiting. Gastrointestinal tract: Morphine relieves diarrhea and dysentery by decreasing the motility and increasing the tone of the intestinal circular smooth muscle. It can also increase biliary tract pressure due to contraction of the gallbladder and constriction of the biliary sphincter. Cardiovascular: Morphine has no major effects on the blood pressure or heart rate except at large doses, when hypotension and bradycardia may occur.

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However, physicians reactions are rate-related, are mild, and occur in only 5-15% of should be aware of weight changes in growing children and adjust infusions. They should be obtained whenever a pain, nausea, breathing dif culties, chills, ushing, rash, anxiety, signi cant infection occurs or when the clinical response to 572,579 low-grade fever, arthralgia, myalgias, and/or headache. After the fth infusion, a Slowing or stopping the infusion for 15-30 minutes will steady state will have been achieved, and the dose or dosing reverse many reactions. Oral hydration prior to the infu increase over baseline IgG level has been shown to signi cantly sion is often helpful. The reactions may be due to complement activity caused 571 trough levels in different patients having similar body mass. Another possible body mass (particularly in children) and/or the possibility of mechanism includes the formation of oligomeric or polymeric protein-losing conditions, and dose adjustments should be made IgG complexes that interact with Fc receptors and trigger the accordingly. When initiating therapy, patients with extremely release of in ammatory mediators. The Immune De ciency Foundation Some centers use an initial dose of 1 g/kg administered survey found that 34% of reactions occurred during the rst slowly in agammaglobulinemic patients. Currently available immunoglobulin products and their properties Refri Pathogen Dosage geration Filtration Osmolality IgA Stabilizer or inactivation/ Route/product formulation Diluent required However, this paraproteinemia, increased blood viscosity, hypercholesterole adverse event appears to occur much less frequently than origi mia, and hypertension. As these devices have the Prompt diagnosis and treatment of these events are required to potential to cause additional adverse events, their use for the sole 35 ensure patient safety. These products include a 16% prep ability of the immunoglobulin administered subcutaneously 596 597,598 600 aration, a 20% formulation, and two 10% products that compared to intravenously. The 16% been standard in Europe or in other reported experiences with 595,603,607,618,620 preparation was discontinued by the manufacturer in 2011. The subtleties comparing the use and nonuse of the 629 globulin on a monthly basis. Although designed for giving the to conversion factor are beginning to be speci cally evaluated. A statistical analysis of all reported trials to children and adults, including pregnant women and the elderly date, however, was able to correlate IgG level with the prevalence 592,595,596,602-616 566 population. For at-home administration, patients some patients may bene t from receiving smaller doses several should have access to containers for biological waste and sharp times a week due to personal preference or improved toler 627 607,621,634,635,638 object disposal. Steady-state serum IgG no currently available guidance and that can potentially put pa levels should be monitored periodically after approximately tients at risk for harm. First, numerous studies have demonstrated an enhanced 627 used for monitoring patient adherence. This bene t results in greater patient satisfaction and fewer Treatment considerations for route of administra missed days of work or school for infusion-clinic appoint 620 tion. As immune, in ammatory, and neuromuscular condi 5-7,422,423,516,603,614,655-658 mentioned earlier, none of these studies have documented proced tions. It from the International Union of Immunological Societies Expert Committee for should be noted that while anecdotal reports of the utility of Primary Immunode ciency. High vs low-dose immunoglobulin therapy in the long-term treatment of X-linked agammaglobulin emia. Impact of trough IgG on pneumonia incidence in primary immunode ciency: A meta-analysis of clinical Immunoglobulin therapy is essential for a broad array of studies. B-cell function in severe combined immunode ciency immunoglobulin has diverse therapeutic mechanisms of ac after stem cell or gene therapy: a review. The different extent of B and T cell immune reconstitution after hematopoietic grow. Intravenous immunoglobulin ther applied where it is most supported by evidence and where it apy for antibody de ciency. Bene t considered in this document, as well as the recommendations of intravenous IgG replacement in hypogammaglobulinemic patients with chronic based therein, should be viewed as currently relevant but sinopulmonary disease. Common variable immunode ciency: clinical likely to change given ongoing research and cumulative and immunological features of 248 patients. Immunoglobulin therapy to control lung damage in patients with common vari able immunode ciency.

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Prevention of body shape changes involves helping people to understand common risk factors and how to use simple common-sense approaches to protect themselves and the people they care for. The legs will then either fall together and to one side (this is described as wind sweeping) or fall outwards into abduction or fall inwards into adduction. The neck may extend backwards taking head behind midline, or fex forward taking the head in front of midline or it may side fex and rotate taking the head to the side of midline. The position of the head is particularly important when considering the ability to eat and drink and for the person to be able to communicate. People with body shape changes often have arms held in a very fexed (bent) or extended (straightened positions). What do you think would happen to your body shape if you had to sit like this all day every day for a month His back has started to take on a rounded shape and he fnds it diffcult to stand tall and straight. He fnds it hard to sit on the foor with his legs straight in front of him and play with his young children. This is because his hips and knees are in a fexed position for long periods of time at work. This is because her calf muscles remain in a shortened position with high heels on. She needs more length in her calf muscles to strike the foor with her heel when walking barefoot. Each time we change position, gravity acts differently on different parts of the body. If the position is asymmetrical, gravity will increase the asymmetry and perhaps make it permanent. She tends to take more weight through her right buttock so that she can lean her right elbow on her arm rest and operate her hand control. We see fewer body shape distortions in the general population than in people with additional health problems. The impact of some of these additional health problems are described in the following stories. She is becoming fearful of walking and, as her activity levels reduce, so does her muscle strength. She spends increasing amounts of time in bed or sitting in a limited number of destructive positions (positions in which we stand, sit and lie that will lead to body shape changes). The causal link between contractures and immobility goes unrecognised by Mrs Reynolds, her family and the healthcare practitioners they come into contact with. Her arthritic knees become more painful, she is dependent on her husband to bring her food and drink, and the position of her head makes it diffcult to swallow. It is decided that institutional care is the only viable option, due to the complexity of her needs.

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Medial to lateral at cervical level: Sacral, lumbar, integration) thoracic, and cervical respectively. Central canal to dorsum (anterior to posterior): Touch, reflex) tone and synergy) position, movement, vibration and pressure 3. Spinothalamic tract As the fibres cross in the spinal cord, the lower limb fibres are placed more laterally, and the upper limb fibres which supplies the ventral part of the cord and a circum are placed more medially at the cervical level. Vascular Syndromes of Spinal Cord Blood Supply of the Spinal Cord Anterior Spinal Artery Syndrome Spinal cord is supplied by one anterior spinal artery (anterior 2/3 of the cord) and a pair of posterior spinal Causes arteries (posterior 1/3 of the cord). Atherosclerosis of the aorta and its branches Spinal cord arterial supply is augmented by radi 4. Following repair (coarctation of aorta) artery anastomoses with the anterior spinal artery and 8. Vertebral artery dissection the posterior branches of the radicular artery anasto 9. The largest radicular artery arises from the aorta in the lower Clinical Features thoracic or upper lumbar region (artery of Adamkiewicz) and is the major source of blood supply 1. Radicular or girdle pain majority of people, enters the spinal cord from the left 3. The anterior spinal artery gives a sulcal branch below the level of the lesion 570 Manual of Practical Medicine Fig. The longitudinal plane lies at the junction of the Posterior Spinal Artery Syndrome anterior spinal artery and posterior spinal artery at all the levels of spinal cord (pyramidal tract is Clinical Features situated in this area and hence vulnerable). Loss of proprioception and vibration sense below the level of lesion Venous Drainage 2. Anteroposterior or Sagittal diameter (mm) Region Minimum Average Maximum Cervical Canal Stenosis Cervical the sagittal diameter is < 11 mm or less than 7 mm with C 16 22 31 neck in extension. Transverse myelitis is almost always due to infective, immunoallergic or demyelinating causes. Infiltration of Reticulosis, leukaemic deposits Traumatic Lesions of the Spinal Cord the meninges in meninges. Cystic lesions Arachnoid cyst and parasitic cyst Concussion (hydatid cyst, cysticercosis) It means transitory loss of sensory and motor functions 4. Whiplash or Flexion Extension Injury the clinical features are mainly due to damage to the Spinal Syphilis soft tissues, (muscle and ligaments) and stretching of It affects the spinal cord nerve roots than actual trauma to the spinal cord itself. Spinal endarteritis: It manifests as a dissociated upper limbs than the lower limbs with varying degree sensory loss (due to thrombosis of anterior spinal of sensory loss) are due to dislocation of the vertebral artery) bodies at C5 and C6 cervical levels (severe hyperexten 4. The recovery (motor and sensory) is first in the legs, then in the upper limbs and finally in the hands. Pain and hyperpathia due to irritation of nerve roots (lightning pain) Syphilis 2. Sensory loss (interruption of reflex arc) and sensory ataxia due to posterior column involvement. It is defined as a suppurative (cranio-pachymeningitis) infection of the epidural space. Multiple cranial nerve palsies, headache, confusion, are furunculosis of the back or scalp, bacteraemia or impairment of memory and optic atrophy (cerebral minor back injury. It presents as an unexplained fever leptomeningitis) can occur of several days to two weeks duration, with mild spinal 3. Hemiplegia (cerebral endarteritis) backache and local tenderness, later causing radicular 4.

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