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There are approximately 160 lymph to clear each region prior to moving to the next region; nodes located in this region and they are responsible for this requires feeling the tissue as its integrity improves. Make note of the Manual lymph drainage relaxes the sympathetic nervous clavipectoral fascia covering the clavicle, coracoid pro system as deep abdominal breathing stimulates the para cess, and axilla; it merges with the skin of the axillary sympathetic nervous system. Gently place the length more effective if you and your patient are relaxed and of 3? If the patient reports pain, your pressure is treatment to quiet the lymphatic system. Slowly move your whole access to a tape measure, extra bandaging products, and hand in large circles stimulating lymph nodes to release handouts for skin care and exercise. Remind your patient the modality you are preparing to use and the patient of what it felt like initially. This is important ask for permission to place your hands on the breasts, for the patient to feel because she will learn to perform buttocks, and inner thigh. Oftentimes the left side is more congest determined that her inguinal lymph nodes were func ed than the right, especially when lower extremities are tional. The thoracic duct is and drains tissue from below the waist bilaterally and the responsible for draining the lower extremities. Once the left lower extremity returned to nor surgery, diverticulitis, aortic aneurism, acute deep vein mal, her treatment program changed from treatment of thrombosis, pregnancy, or pain. Incidentally, her left lower in the abdomen, visualize the depth of the lymph nodes extremity swelling has never returned. It is important to located within the greater omentum and gently engage understand the anatomy and physiology to make the best the tissue. Place both hands on the abdomen to feel the clinical decision for your treatment approach. Lower Extremity Lymphedema Pathway Always ask the patient if the pressure is tolerable, and if not, decrease your pressure. Slowly move your hand in circles to stimulate each lymph node to release waste and lymph. Move your hand to the left transverse abdominis muscle and repeat the sequence, follow with the right transverse abdominis muscle, and lastly the ascending colon. If it has not softened, you may have been hasty, either with stationary circles or lack of time in one region. Determine your treatment protocol based on assess ment of the involved extremities and functional lymph node groups. Typical scenarios include one upper ex tremity limb involvement or single or bilateral lower ex tremity involvement. Appearance alone would right lower extremity lymphedema and stage 1 lymph not have indicated she had swelling in her right arm; edema in her left lower extremity. Abdominal, cervical, however, the tissue in the right arm felt congested, heavy, and axillary lymph nodes were intact. Other related was not part of her cancer treatment; therefore, it was health history concerns were celiac disease and Dercum 12 disease consisting of painful adipose cysts imbedded in connective tissue throughout her entire body. Right Upper Extremity Lymphedema Pathway rare disease in active autoimmune response. Left Upper Extremity Lymphedema Pathway nodes are sometimes removed following excision of cancer in an associated region. Stimulate the lymph node groups in each region by placing the palm of your hand on the lymph node group and moving your hand in slow stationary circles covering the complete range of lymph nodes. Stimulate the functioning lymph node groups that are ipsilateral and contralateral to the affected limb. In an affected right leg, and chemotherapy and right upper extremity lymphede clear lymph node groups in the contralateral left inguinal ma. She was a university professor who repetitively used region and ipsilateral right axilla. Gently assess in the abdomen that will assist in processing the lymph the tissue restrictions in the axilla and inguinal region, and? Clinical decisions are based on understanding the demonstrate the restrictions to your patient. Fluid transport can occur from the axilla to a very small number of lymph nodes located in this re the inguinal region or vice versa. Manual lymph drainage on the upper extremity is anastomoses, following the direction of normal? In other words, initiate your stroke on the upper your hand at the waist and direct your strokes from the arm at the elbow to the shoulder, follow with the lower waist to the inguinal region using the ?pump. Begin with the web of your hand at the vertical plane parallel to the lymph vessels. If the skin becomes red, you are us ter 5 to 10 repetitions, place your hand at the axilla with ing too much pressure and injuring lymph vessels. Your your hand directed toward the pelvis, and repeat the se hand stays in contact with the skin. If you choose to mobi progression, you apply a slight pressure, and during the lize lymph? You repeat the sequence to the the trunk and slightly push toward the axilla 2 cm, return shoulder. The lymph system moves very slowly; there your position with the web of your hand 2 cm higher and fore, strokes should be performed slowly. After 5 to 10 drainage for the medial upper arm is performed by plac repetitions, place the web of your hand at the inguinal ing your? The most tinually returning to the medial arm, mobilizing lymph common treatment plan in a patient with lower extrem drainage to the lateral arm with 5 to 10 strokes as you ity lymphedema is to direct? Step 3 begins at the wrist with the ized technique that mimics an inchworm with the hand. Right upper extremity lymphedema will require mine the number of pathways you will drain. Be you will have two pathways for the anterior and two for gin with your hand raised, thumb and? Drag your thumb across Beginning at the distal metacarpals in (Step 4), use your the skin to your? Relax your hand, raise your position tically parallel to the lymph vessels from distal to proxi to? In this stroke on the upper anterior and posterior trunk or low the clinic, the prone position is often used. Repeat Step er anterior and posterior trunk will be based on the involved 2 then Step 1. If a patient has right low ly and proximally at the elbow to the lateral upper arm er extremity lymphedema, choose to mobilize tissue from from the elbow to the axilla. If both legs are lateral upper arm from the proximal elbow to the shoul involved, mobilize the? Repeat Steps 3 and 4 on the posterior lower arm and with a pathway from the left waist to the left axilla to avoid palmer surface of the hand. It is helpful to of spiro-strokes, pump, or scoop from the limb to the new draw a picture to determine the pathway for lymph? Step 1 begins with spiro-strokes on the anterior thigh from the proximal knee to the iliac crest with 10 to 15 repetitions. Left Lower Extremity Lymphedema Pathway anterior thigh to the lateral hip with the exception of a patient with functional lymph nodes in the inguinal re gion. In Step 2, place your hand on the medial thigh proximal to the knee and mobilize lymph at an upward angle to the anterior thigh. Step 4 begins in the lower leg proximal to the ankle using the spiro-strokes or the pump. In Step 5, place your hand on the lateral lower leg as you stretch the tissue from lateral to medial with an upward motion. Step 7 consists of spiro-strokes from distal to proximal along the length of the toes. Position the patient in prone to manip ulate lymph drainage from the posterior side. Begin with spiro-strokes (Step 1) above the posterior knee from distal upper thigh to proximal lateral upper thigh; also include the buttocks with spiro-strokes from the gluteal fold to the iliac crest.

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It was like a great bee come home from some field where the honey is full of poison wildness, of insanity and nightmare, its body crammed with that over-rich nectar and now it was sleeping the evil out of itself. Nights when things got dull, which was every night, the men slid down the brass poles, and set the ticking combinations of the olfactory system of the Hound and let loose rats in the firehouse area-way, and sometimes chickens, and sometimes cats that would have to be drowned anyway, and there would be betting to see which the Hound would seize first. Three seconds later the game was done, the rat, cat, or chicken caught half across the areaway, gripped in gentling paws while a four-inch hollow steel needle plunged down from the proboscis of the Hound to inject massive jolts of morphine or procaine. But now at night he lay in his bunk, face turned to the wall, listening to whoops of laughter below and the piano-string scurry of rat feet, the violin squeaking of mice, and the great shadowing, motioned silence of the Hound leaping out like a moth in the raw light, finding, holding its victim, inserting the needle and going back to its kennel to die as if a switch had been turned. The Hound half rose in its kennel and looked at him with green blue neon light flickering in its suddenly activated eyebulbs. It growled again, a strange rasping combination of electrical sizzle, a frying sound, a scraping of metal, a turning of cogs that seemed rusty and ancient with suspicion. He saw the silver needle extended upon the air an inch, pull back, extend, pull back. Below, the Hound had sunk back down upon its eight incredible insect legs and was humming to itself again, its multi-faceted eyes at peace. Behind him, four men at a card table under a green-lidded light in the corner glanced briefly but said nothing. Beatty stood there looking at him steadily with his eyes, while his mouth opened and began to laugh, very softly. And as many times he came out of the house and Clarisse was there somewhere in the world. Once he saw her shaking a walnut tree, once he saw her sitting on the lawn knitting a blue sweater, three or four times he found a bouquet of late flowers on his porch, or a handful of chestnuts in a little sack, or some autumn leaves neatly pinned to a sheet of white paper and thumb tacked to his door. One day it was raining, the next it was clear, the day after that the wind blew strong, and the day after that it was mild and calm, and the day after that calm day was a day like a furnace of summer and Clarisse with her face all sunburnt by late afternoon. 0 But everyone I know is either shouting or dancing around like wild or beating up one another. But they all say the same things and nobody says anything different from anyone else. Fireman in Seattle, purposely set a Mechanical Hound to his own chemical complex and let it loose. The lawn was empty, the trees empty, the street empty, and while at first he did not even know he missed her or was even looking for her, the fact was that by the time he reached the subway, there were vague stirrings of un-ease in him. The flutter of cards, motion of hands, of eyelids, the drone of the time voice in the firehouse ceiling ". He could feel the firehouse full of glitter and shine and silence, of brass colors, the colors of coins, of gold, of silver: the unseen men across the table were sighing on their cards, waiting. This country stands ready to defend its-" the firehouse trembled as a great flight of jet planes whistled a single note across the black morning sky. At any moment, Beatty might rise and walk about him, touching, exploring his guilt and self-consciousness. These men who looked steadily into their platinum igniter flames as they lit their eternally burning black pipes. They and their charcoal hair and soot-colored brows and bluish-ash-smeared cheeks where they had shaven close; but their heritage showed. The color of cinders and ash about them, and the continual smell of burning from their pipes. Beatty opening a fresh tobacco packet, crumpling the cellophane into a sound of fire. Their names leapt in fire, burning down the years under his axe and his hose which sprayed not water but kerosene. And, again, he saw himself in a green park talking to an old man, a very old man, and the wind from the park was cold, too. It was a flaking three-storey house in the ancient part of the city, a century old if it was a day, but like all houses it had been given 32 a thin fireproof plastic sheath many years ago, and this preservative shell seemed to be the only thing holding it in the sky. Beatty, Stoneman, and Black ran up the sidewalk, suddenly odious and fat in the plump fireproof slickers. They crashed the front door and grabbed at a woman, though she was not running, she was not trying to escape. She was only standing, weaving from side to side, her eyes fixed upon a nothingness in the wall as if they had struck her a terrible blow upon the head. Stoneman held out the telephone alarm card with the complaint signed in telephone duplicate on the back "Have reason to suspect attic; 11 No. The men were making too much noise, laughing, joking to cover her terrible accusing silence below. She made the empty rooms roar with accusation and shake down a fine dust of guilt that was sucked in their nostrils as they plunged about. Books bombarded his shoulders, his arms, his upturned face A book alighted, almost obediently, like a white pigeon, in his hands, wings fluttering. In the dim, wavering light, a page hung open and it was like a snowy feather, the words delicately painted thereon. In all the rush and fervor, Montag had only an instant to read a line, but it blazed in his mind for the next minute as if stamped there with fiery steel. They fell like slaughtered birds and the woman stood below, like a small girl, among the bodies. His hand had done it all, his hand, with a brain of its own, with a conscience and a curiosity in each trembling finger, had turned thief. She opened the fingers of one hand slightly and in the palm of the hand was a single slender object. Captain Beatty, keeping his dignity, backed slowly through the front door, his pink face burnt and shiny from a thousand fires and night excitements. On the front porch where she had come to weigh them quietly with her eyes, her quietness a condemnation, the woman stood motionless. The woman on the porch reached out with contempt for them all, and struck the kitchen match against the railing. They sat there looking out of the front of the great salamander as they turned a corner and went silently on. He felt one hand and then the other work his coat free and let it slump to the floor. He could feel the poison working up his wrists and into his elbows and his shoulders, and then the jump-over from shoulder-blade to shoulder-blade like a spark leaping a gap. And his eyes were beginning to feel hunger, as if they must look at something, anything, everything. He lay far across the room from her, on a winter island separated by an empty sea. But Montag said nothing and after a long while when he only made the small sounds, he felt her move in the room and come to his bed and stand over him and put her hand down to feel his cheek. There was a tiny dance of melody in the air, her Seashell was tamped in her ear again and she was listening to far people in far places, her eyes wide and staring at the fathoms of blackness above her in the ceiling. He held both hands over his eyes and applied a steady pressure there as if to crush memory into place. It was suddenly more important than any other thing in a life-time that he knew where he had met Mildred. And me not sleeping, tonight or tomorrow night or any night for a long while; now that this has started. And he thought of her lying on the bed with the two technicians standing straight over her, not bent with concern, but only standing straight, arms folded. For it would be the dying of an unknown, a street face, a newspaper image, and it was suddenly so very wrong that he had begun to cry, not at death but at the thought of not crying at death, a silly empty man near a silly empty woman, while the hungry snake made her still more empty. And the uncles, the aunts, the cousins, the nieces, the nephews, that lived in those walls, the gibbering pack of tree-apes that said nothing, nothing, nothing and said it loud, loud, loud. Music bombarded him at such an immense volume that his bones were almost shaken from their tendons; he felt his jaw vibrate, his eyes wobble in his head. When it was all over he felt like a man who had been thrown from a cliff, whirled in a centrifuge and spat out over a waterfall that fell and fell into emptiness and emptiness and never-quite-touched-bottom-never-never-quite-no not quite-touched-bottom. Even though the people in the walls of the room had barely moved, and nothing had really been settled, you had the impression that someone had turned on a washing-machine or sucked you up in a gigantic vacuum. Behind him, Mildred sat in her chair and the voices went on again: 42 "Well, everything will be all right now," said an "aunt.

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Humoral immunity involves soluble proteins References found in serum (antibodies) that can be transferred to a recipient and subclasses comprising generally 2-5% of the total Ig. Every cell in a vertebrate organism expresses the class I Major a polyclonal antibody. This is a general description of the cellular immune Source IgG concentration (approximate) are identical, providing a source of homogeneous antibody having straightforward process involving immunization of animals and response, which targets intracellular pathogens such as viruses Ascites 2-10mg/mL reliance upon their immune systems to levy responses that result or bacteria (non-self) and cancer cells (altered self). However, while B lymphocytes can be isolated from suspensions of spleen or lymph node cells excised Serum 10-16mg/mL in biosynthesis of antibodies against the injected molecule. Even so, several factors affect the probability of inducing an immunized the humoral response targets extracellular antigens. B-lymphocytes use membrane IgM (mIgM) to bind antigen in its be cultured directly to produce antibody in useful amounts. Crosslinking of many mIgM and antigen molecules that maximizes production of a specifc immune response by the occurs (capping) and the complex is then taken into the cell by animal. This endosome then fuses with a lysosome and the resulting endolysosome digests the antigen Antibody production is conceptually simple. The T cell receptor of Molecular weight 150,000 900,000 320,000 (secretory) suites of specifc antibodies against an injected antigen. Carbohydrate (approximate) 3% 12% 10% 12% 13% Distribution Intravascular and Mostly intravascular Intravascular and secretions Basophils and mast cells in Lymphocyte surface For example, small compounds (drugs or peptides) are not extravascular saliva and nasal secretions suffciently complex by themselves to induce an immune Function Secondary response Primary response Protect mucous membranes Protect against parasites Unknown response or be processed in a manner that elicits production of specifc antibodies. Adjuvants can be mixed and injected with an immunogen to increase the intensity of the immune response. Carrier protein conjugation, use of adjuvants and other issues relating to preparation of samples for injection are described in this section on antibody production. Procedures for generating, purifying and modifying antibodies for use as antigen-specifc probes were developed during the 1970s and 1980s and have remained relatively unchanged since Harlow and Lane published their classic book ?Antibodies: A Laboratory Manual? in 1988. The copper-containing polypeptide belongs to a group Successful generation of antibodies depends upon B-lymphocytes lipids, nucleic acids and proteins. Carbohydrates are immuno or other haptens that are not suffciently large or complex on of non-heme proteins called hemocyanins, which are found in to bind, process and present antigen to T helper lymphocytes, genic only if they have a relatively complex polysaccharide their own to induce an immune response and produce antibodies. Lipids usually are not immunogenic but can be immunogenicity to the conjugated hapten, resulting in antibodies components of the immune system. Because of their structural immunogenicity, solubility, and availability of useful functional to the animal systems typically used to produce antibodies. Peptides are most often conjugated to carrier Properties Determining Immunogenicity and carrier. Because an antibody response will be directed against attachment of haptens using a variety of crosslinking techniques. There are three characteristics that a substance plan carefully how hapten-specifc antibodies will be identifed carrier protein for immunogen preparation. Although the large must have to be immunogenic: foreignness, high molecular Haptens vs. To create the best protein is sometimes diffcult to work with because it has limited weight and chemical complexity. Foreignness is required so Peptides and other small molecules that are used as antigens immunogen, it may be benefcial to prepare the conjugates with solubility, the commercial availability of stabilized and pre-activated that the immunized animal does not recognize and ignore the are referred to as haptens. They are able to act as recognition several different carriers and with a range of hapten:carrier formulations make it convenient to use. Thermo Scientifc Imject Mariculture Keyhole Limpet Hemocyanin are not immunogenic to that same individual and are only poorly selves stimulate the necessary immune response. For very small antigens, practically the entire vested directly from the natural environment. Compounds smaller than this can often be bound antibodies directed at numerous epitopes. Giant keyhole limpets by mIgM on the surface of the B-lymphocyte, but they are not are mixtures of serum immunoglobulins and collectively are are raised in tanks and harvested (marine culture or ?mariculture?) large enough to facilitate crosslinking of the mIgM molecules. Monoclonal where they are occasionally milked of some of their fuids, similar this crosslinking is commonly called ?capping? and is the signal antibodies by defnition contain only a single antibody clone and to humans donating blood. Finally, some degree of chemical complexity is required for Specifc antibodies can be generated against nearly any a compound to be immunogenic. For example, even high suffciently unique chemical structure, either natural or synthetic, molecular weight homopolymers of amino acids and simple as long as the compound is presented to the immune system polysaccharides seldom make good immunogens because they in a form that is immunogenic. The resulting antibodies may lack the chemical complexity necessary to generate an bind to epitopes composed of entire molecules. To overcome diffcult in handling, we have derivatized cantly better solubility provides greater fexibility in immunogen nogenic. Poly(ethylene glycol) pH conditions for coupling peptides, proteins and other haptens residues, 30 to 35 of which have primary amines that are capable mary amines provides for a greater number of antigen molecules has several chemical properties that make it especially useful in using crosslinking methods. Only by using different carrier proteins in the immunization and screening/purifcation steps can one be Figure 3. In vivo, the anti O body response increased and remained elevated for an extended O period of time. Also Because most proteins contain both exposed lysines and A peptide synthesized with a terminal cysteine residue has a Glutaraldehyde can be used to crosslink peptides and carrier known as egg albumin, ovalbumin constitutes 75% of protein in carboxyl groups, immunogen formation with the carbodiimide sulfhydryl group that provides a highly specifc conjugation proteins via amines on the respective polypeptides. For example, the randomly targets lysine residues or the N-terminus of a peptide used as a secondary (screening) carrier rather than for immuni for protein-carrier and peptide-carrier conjugations. The protein also with available carboxyl groups on either the protein carrier or group that will react with free sulfhydryls, plus and a succinimidyl upon the peptide amino acid composition. By reacting the possesses more than one primary amine), the opportunity for carboxyl groups. These groups can be used as targets for con this intermediate then reacts with a primary amine to form reagent frst to the carrier protein (with its numerous amines) variable antigen presentation (orientation) and high loading jugation with haptens. Ovalbumin exists as a single polypeptide an amide bond and a soluble urea by-product (Figure 4). If longer spacer arms are desired, least in their N and C-termini, respectively). For example, proteins and peptides have primary may actually enhance the immunogenicity of the peptide, Any protein can be maleimide-activated in this manner to allow O O amines (the N-terminus and the side chain of lysine residues), effecting a greater antibody response. Purchasing many primary amines in a carrier protein that are used to couple quality-tested, stabilized, maleimide-activated carrier proteins haptens via a crosslinking reagent. Carrier proteins possess numerous (tens to hundreds) of primary amines per molecule. Therefore, each carrier protein molecule receives many maleimide activations and can conjugate many peptide haptens. Yet, conjugation to While each carrier protein possesses specifc differentiating traits, conjugate sulfhydryl-containing haptens. For a number of reasons, a carrier protein is necessary if they are to be made immunogenic they are rarely compared across the same parameters. Below is a this is an especially effective and popular strategy for conjugating and allow production of antibody. Our Imject haptens containing sugar groups or polysaccharide chains can be immune response. Maleimide-Activated Carrier Proteins are prepared using a very conjugated by reductive amination to primary amines on carrier H reliable procedure, and each lot is tested to confrm that a high proteins. A dilution series of L-cysteine is prepared immunogen, care must be taken to prevent altering the hapten that can Participate in the Mannich Reaction related Blue Carrier Protein products have more than suffcient (1mg/mL to 0. Examples of Mannich Reaction and active hydrogen compounds Assay Buffer is added to the test sample. Samples are incubated for the peptides and other haptens allows for the addition of unique 15 minutes with 20?L of a 6. They contain a molar excess of maleimide for coupling cysteine containing haptens (peptide or proteins). Activation levels (moles of maleimide per gram of carrier protein) were determined with a cysteine coupling assay. Thus, we compared our various carrier protein products Peptide crosslinker and exchange buffer components before using the pre antibodies by the immunized host animal.

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Outpatient treatment appears safe provided the patient is at low risk of an adverse outcome. Some patients also received mechanical thromboprophylaxis but this was deemed to be unlikely to contribute to bleeding risk. The rate of re-operation to control bleeding in recipients of any heparin was, however, very low (0. One + 1 weakness of this analysis was that the doses of the drugs used were not considered and nor were the regimens used (preoperative versus postoperative initiation and duration of treatment). Of 276 major bleeds, 37 were fatal giving a case fatality for major haemorrhage of 13. Antithrombotic drugs 1 increase the risk of vertebral canal bleeding in patients who undergo central neuraxial block 4 and this may result in permanent neurological injury due to compression of the spinal cord or cauda equina. Assessment of cases using a clinical scoring system allows identification of low-, intermediate and high-risk patients. There is some evidence for warfarin-associated osteoporosis in long term users of warfarin. Mechanisms should be in place to review care provided against the guideline recommendations. Local arrangements should then be made to implement the national guideline in individual hospitals, units and practices. Successful implementation and audit of guideline recommendations requires good communication between staff and multidisciplinary team working. The guideline development group has identified the following as key points to audit to assist with the implementation of this guideline. The main searches were supplemented by material identified by individual members of the development group. Ms Mary Deas Distribution and Office Coordinator Mrs Karen Graham Patient Involvement Officer Mrs Lesley Forsyth Events Coordinator Mr Stuart Neville Publications Designer Ms Gaynor Rattray Senior Guideline Coordinator 19. The guideline group addresses every comment made by an external reviewer, and must justify any disagreement with the reviewers? comments. Invasive procedures to include: general and gynaecological surgery, orthopaedic surgery, urological surgery, neurosurgery, cardiothoracic surgery, peripheral vascular surgery, minimal access surgery, central venous catheters. Consider mechanical and pharmaceutical treatments; alternative/ homeopathic treatments. Mechanical: graduated elastic compression stockings, intermittent pneumatic compression devices, mechanical foot pumps, venal cava filters. Date of admission Date of first assessment Assessed by Designation Surgical patients start here Medical patients start here Does the patient have active cancer/receiving cancer Is the patient expected to have No treatment? The chance of us failing to detect a clot has however been estimated to be very low, (typically less than 1 in 200 for people like yourself who have a sore leg). Although these risks are uncommon, they mean we should use the drugs only when there is a clear benefit to outweigh these risks. Venous thromboembolism risk and prophylaxis extremities: an analysis of a defined patient population in Sweden. Reduction in fatal thromboembolism on the complications of arthroplasty of the lower pulmonary embolism and venous thrombosis by perioperative limb. The epidemiology of venous thromboembolism hospital patients: are we detecting enough deep vein thrombosis? The report of of the hospital incidence and case-fatality rates of deep vein the National Confidential Enquiry into Perioperative Deaths thrombosis and pulmonary embolism. Ageno W, Agnelli G, Imberti D, Moia M, Palareti G, Pistelli R, et London: the Stationary Office; 1998. Comparison of clinical and postmortem Illustrative reference ranges by age, sex and hormone use. The seventh report of the Risk of venous thromboembolism in users of hormone replacement Confidential Enquiries into Maternal Deaths in the United therapy. The value of family history as a risk indicator for venous women with breast cancer. Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert epidemiological studies. Venous thromboembolism and mortality inherited thrombophilic abnormalities and central venous catheter associated with recombinant erythropoietin and darbepoetin thrombosis in patients with cancer: a meta-analysis. Blom jW, Vanderschoot jP, Oostindier Mj, Osanto S, van der Meer G, Nicol P, et al. Cardiovascular disease and steroid at time of first venous thrombosis in thrombophilic families. Tooher R, Middleton P, Pham C, Fitridge R, Rowe S, Babidge W, 1999;354(9190):1610-1. Ann Surg 2005;241(3):397 contraceptives and risk of venous thrombosis: meta-analysis. Electronic alerts to prevent venous thromboembolism replacement therapy and risk of venous thromboembolism in among hospitalized patients. The risk of venous thromboembolic stockings for prevention of deep vein thrombosis. Cochrane disease associated with adjuvant hormone therapy for breast Database of Systematic Reviews: Reviews 2010 Issue 7 john Wiley carcinoma: a systematic review. Knee versus Thigh Length Graduated Compression Stockings for Prevention of pulmonary embolism and deep vein thrombosis Prevention of Deep Venous Thrombosis: A Systematic Review. Health Bull 2001;59(1):57 Prevention of Fatal Postoperative pulmonary embolism by low 9. Heparin and low-molecular-weight heparin: thromboprophylaxis in colorectal surgery - an update. Colorectal mechanisms of action, pharmacokinetics, dosing, monitoring, Dis 2005;7(2):122-7. Low-molecular-weight heparin vs unfractionated heparin comparison of danaparoid with dextran 70 in the treatment of for perioperative thromboprophylaxis in patients with cancer: heparin-induced thrombocytopaenia with thrombosis: a clinical a systematic review and meta-analysis. Survey of use of thromboprophylaxis for with low-molecular-weight heparin or unfractionated heparin. Risk of compartment syndrome and aortic venous thromboembolism following total hip replacement. Lower limb (well leg) compartment and pharmacological prophylaxis for prevention of venous syndrome after urological pelvic surgery. Elastic stockings in the prevention venous thromboembolism: findings in a large prospective study. Venous College of Chest Physicians Evidence-Based Clinical Practice thromboembolism: reducing the risk of venous thromboembolism Guidelines (8th Edition). Venous thromboembolism: reducing the risk of venous thromboembolism after different elective or urgent surgical venous thromboembolism (deep vein thrombosis and pulmonary procedures. Results of a multicenter, prospective, Acenocoumarol, fondaparinux, dabigatran and rivaroxban. Expert randomized, controlled study with a low molecular weight Rev Pharmacoecon Outcomes Res 2007;7(1):49-58. Variables associated with postoperative deep venous with vitamin K antagonists: A meta-analysis. Venous thromboembolism in patients than aspirin in the prevention of venous thromboembolism after undergoing laparoscopic and arthroscopic surgery and in leg casts. Roderick P, Ferris G, Wilson K, Halls H, jackson D, Collins R, Pract Res 2006;36(3):214-7. Potent anticoagulants are associated with a higher all-cause thromboprophylaxis after total knee arthroplasty. Extended duration rivaroxaban versus short-term enoxaparin compression stockings in association with fondaparinux in for the prevention of venous thromboembolism after total hip surgery of the hip. Comparison of warfarin, low-molecular-weight venous thromboembolism following total hip or knee arthroplasty. Adjusted versus fixed-dose subcutaneous heparin in low-molecular-weight heparin (nadroparin) and mechanical the prevention of deep-vein thrombosis after total hip replacement. Prevention of postoperative venous thrombosis: a randomized plantar venous compression in prevention of deep venous trial comparing unfractionated heparin with low molecular weight thrombosis after total hip arthroplasty. Preoperative vs postoperative initiation of low-molecular of heparin and foot impulse pump. Low-molecular-weight heparin by using intermittent compression of the plantar venous plexus.

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Preparation Know the facts and potential management plan Arrange for privacy, sufficient seating and avoidance of interruptions Whenever possible offer the patient the chance to have a close family member or friend present 2. Assess the existing level of understanding (may need repeating as further information given) ?What do you understand about your illness/what is happening? Check if more information wanted and at what level ?Do you want to go on or is that enough for now? Know when to stop Be clear and simple, avoiding jargon, and above all be gentle Avoid assumptions about understanding i. Summary and plan Summarise what has been said, emphasising the positive Outline future treatment if appropriate, using written or printed material if possible. Make arrangements for further contact Offer early review Ask who may be told of the diagnosis/information 10. Denial is not necessarily unhealthy and can be normal, as in the first stage of accepting bad news. It may be appropriate to explore the denial where it has created situations that are harmful such as preventing appropriate treatment, adequate symptom control, or future planning for dependents. Many people have a good understanding of the situation but do not wish to talk about it Is other health professionals? denial contributing? Management Gently explore what the person understands of what they have been told Using the framework outlined in Breaking Bad News (p93), gently move the person towards a better understanding of reality, particularly with regard for the particular need iden=fied for challenging the denial. It is often well intentioned, acting in what is believed to be the best interests of the patient. However, this inevitably creates tension because, ethically and legally, the patient has the right to information and to authorize disclosure of information to family. Respect and accept complex family dynamics Do not presume to know what is best for families. Occasionally patients collude with professionals to withhold information from their family. This is more difficult as the patient has to give permission for disclosure of information, however the principles are the same as above exploration of reasoning; explanation of consequences; reassurance of sensitive handling and offer facilitation. Psychological, emotional, spiritual and social needs of both patient and their family/carers should be addressed. This holistic assessment is important in ensuring that the patient and family have optimal support in any care setting. It also ensures that discharge planning is effective (hospital/hospice staff should check that these plans are acceptable to the patient, family, carers and Primary Health Care Team). During assessment it should become apparent whether further expert professional help is required for psychological, spiritual and social care. It requires providing a person with the space to talk about and explore their belief system. Facilitating these conversations allows for the clinician or chaplain to address distress arising from any crisis in their belief system that has been caused by their experience of having a life-shortening illness. This does not necessarily require specialist help all health professionals should be prepared to make initial assessments and identify these issues. Spiritual distress When a person experiences a life crisis they will look to their spiritual values, beliefs, attitudes and religious practices to make sense of it. If these do not enable them to cope with the crisis, then they may experience spiritual distress. Offer the support of a chaplain or other spiritual leader particularly if you feel out of your depth or there is a requirement for religious input Basic principle 1. Attend to: Signs of their wishing to explore spiritual issues Ask yourself ?Why am I being told this? Reassure and help with: Good physical care in illness and dying Respect for their integrity, worth and values Information as requested ?Unfinished business? Personal support ?being alongside? Care for family and carers Reviewing of life Arranging provision of spiritual counselling if needed. Attend to yourself: Facing intense feelings or distress can leave us feeling uncomfortable, inadequate, helpless or vulnerable. It is therefore important to explore difficult issues or share concerns with colleagues. Within these groups, each individual will express their cultural attitudes uniquely, as they are influenced by upbringing, background, environment, beliefs and life experience. Cultural attitudes can particularly influence: Language and use of colloquialisms the roles of the family How symptoms or illness are described and understood Attitudes towards expressing emotion and discussing private issues with those outside the family Ethical issues, including autonomy and confidentiality Attitudes towards conventional Western therapies, complementary or alternative therapies, food and diet Attitudes towards pain relief Attitudes towards death and dying Rituals surrounding death (see below) Preferred place of care home, care home, hospital or hospice Acceptance of help and support Health professionals should show their awareness by: Ensuring appropriate language interpretation services are used Demonstrating willingness to listen and a wish to understand cultural differences and implications Meeting specific requirements (such as food, privacy, opportunity to practice religious observances etc. Bereavement has been described in terms of tasks of grief: Initial shock, numbness and disbelief before emotional reality of the loss is felt. Seeing the body after death, attending the funeral or visiting the grave are often important in facilitating acceptance of the reality of the death. The bereaved usually suffer overwhelming periods of sadness as they are faced with the day-to-day reality of their loss. Agitation, restlessness and an inability to concentrate can result from the conflict between this searching and avoiding behavior. Anger may be directed towards the deceased for abandoning them, towards God, or (justly or unjustly) towards professionals. It is common for physical symptoms related to over-activity of the autonomic nervous system to be experienced. As the pangs of grief and anxiety reduce in frequency and severity the bereaved may lose interest and purpose in life. The task of resolution and reorganisation is entered when emotional energy is reinvested in new relationships and activities, although anniversaries often trigger renewed grief. For some, part of the work of grieving may be undergone before the death (anticipatory grieving). A key characteristic of the experience of grief is a pattern of oscillating between periods of intense grief (?waves of grief?/feeling overwhelmed by the loss) and periods of greater stability in which the bereaved person is able to feel a respite from intense feelings as well as being more engaged in life and optimistic (more controlled/ functioning). When feelings and functioning are balanced, there is resilience; when not vulnerability will result. The pattern of oscillating from one state to another will continue for some time and is entirely normal. It can be helpful to explain that this is normal to people so that do not feel that they are constantly ?going back to square one? every time that the grief intensifies again. For most people, no formal psychotherapeutic intervention is needed as their personality, previous life experiences, social network and loving relationship with the deceased enable them to come to terms with their loss, and often to grow personally through it. Often all that is required is a watchful eye to check that their grief is continuing normally. Written information explaining what may be experienced and giving useful contact numbers is often appreciated. Those requiring a greater degree of support may benefit from meeting with a volunteer with training in listening skills and with knowledge of the bereavement theory described here. A chaplain may also be helpful to those who wish to explore changes in their faith in the light of their bereavement. Some find meeting with a group of individuals who have undergone a similar experience can be supportive. The needs of children and adolescents are specific to their stage of development and can be quite complex: they may also benefit from specialist support. Recognition of those likely to develop a complicated grief reaction can also allow early supportive intervention and prevent its development. Risk factors include: Unexpected/untimely death A death experienced as traumatic or unpleasant Ambivalent relationship Excessively dependent relationship Child/adolescent (may be protected/excluded) Social isolation Excessive use of denial, preventing anticipatory grieving Unresolved anger Previously unresolved losses Previous psychiatric illness History of alcoholism/drug abuse Other concurrent stressful life events Some of these complicated grief reactions can be dealt with by the primary health care teams, social workers, psychotherapists or trained counsellors. It is important for all professionals to realise the limitations of their own skills and to identify when to refer to their local specialist bereavement service. It is a consensus guide for all staff working with patients with palliative care needs. The book was adopted by all the Specialist Palliative Care units in Wessex in 1997 with the production of the fifth edition. This edition, the ninth, has been reviewed and revised by clinicians working in the multi-professional specialist palliative care services in the areas listed below under the direction of the Wessex Palliative Physicians. Contributing Community, Hospital and Hospice Specialist Palliative Care Services based in: Basingstoke and Winchester Bath Christchurch and Bournemouth Dorchester Isle of Wight Lymington Poole Portsmouth Salisbury Southampton Swindon Copyright Wessex Palliative Physicians 2019 106 Return to contents page. Ganz University of California, Los Angeles the number of individuals living with a history of cancer is goals in this article are to highlight the importance of psycho estimated at 13.

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It also recommends where shifts are encouraged to help people achieve healthy eating patterns. These analyses will assist professionals and policymakers as they use the Dietary Guidelines to help Americans adopt healthier eating patterns and make healthy choices in their daily lives, while enjoying food and celebrating cultural and personal traditions through food. Now more than ever, we recognize the importance of focusing not on individual nutrients or foods in isolation, but on everything we eat and drink?healthy eating patterns as a whole?to bring about lasting improvements in individual and population health. The body of scientifc literature looking at healthy eating patterns and their impact on disease prevention is far more robust now than ever before. Chronic diet-related diseases continue to rise and levels of physical activity remain low. Progress in reversing these trends will require comprehensive and coordinated strategies, and the Dietary Guidelines is an important part of a complex and multifaceted solution to promote health and help to reduce the risk of chronic disease. The Dietary Guidelines translates science into succinct, food-based guidance that can be relied upon to help Americans choose a healthy eating pattern and enjoyable diet. We believe that aligning with the recommendations in the Dietary Guidelines will help many Americans lead healthier and more active lives. Department Health and Human Services of Agriculture 2015-2020 Dietary Guidelines for Americans Page vii Acknowledgments the U. Department of Agriculture acknowledge the work of the 2015 Dietary Guidelines Advisory Committee whose recommendations informed revisions for this edition of the Dietary Guidelines for Americans. The Departments also acknowledge the work of the departmental scientists, staff, and policy offcials responsible for the production of this document. Policy Document Reviewers/Technical Assistance the Departments acknowledge the contributions of numerous other internal departmental scientists who provided consultation and extensive review throughout the production of this document. Additionally, the Departments acknowledge the external, independent peer reviewers for their work to ensure technical accuracy in the translation of the science into policy. Finally, the Departments would like to acknowledge the important role of those who provided public comments throughout this process. Page viii? 2015-2020 Dietary Guidelines for Americans 2015-2020 Dietary Guidelines for Americans Page ix Executive Summary Page x 2015-2020 Dietary Guidelines for Americans ver the past century, deficiencies based on the preponderance of current diet forms an overall eating pattern. The components of the eating pattern O dramatically decreased, the 2015-2020 edition of the Dietary can have interactive and potentially many infectious diseases have been Guidelines builds from the 2010 edition cumulative effects on health. These conquered, and the majority of the with revisions based on the Scientific patterns can be tailored to an U. At the same Advisory Committee and consideration enabling Americans to choose the time, rates of chronic diseases?many of Federal agency and public comments. A growing of which are related to poor quality body of research has examined the the Dietary Guidelines is designed for diet and physical inactivity?have relationship between overall eating professionals to help all individuals increased. About half of all American patterns, health, and risk of chronic ages 2 years and older and their adults have one or more preventable, disease, and findings on these families consume a healthy, nutritionally diet-related chronic diseases, including relationships are sufficiently well adequate diet. The information in cardiovascular disease, type 2 diabetes, established to support dietary guidance. As a result, eating patterns and their developing Federal food, nutrition, food and nutrient characteristics are However, a large body of evidence now and health policies and programs. It a focus of the recommendations in shows that healthy eating patterns also is the basis for Federal nutrition the 2015-2020 Dietary Guidelines. The 2015-2020 Dietary policymakers and nutrition and health recognize that individuals will need to Guidelines for Americans reflects this professionals. Additional audiences who make shifts in their food and beverage evidence through its recommendations. These Monitoring and Related Research Act, groups, media, the food industry, Guidelines also embody the idea that which states that every 5 years, the and State and local governments. The statute (Public people do not eat food groups and of healthy eating patterns that translate Law 101-445, 7 U. Choose a healthy eating pattern at an appropriate calorie level to help achieve and maintain a healthy body weight, support nutrient adequacy, and reduce the risk of chronic disease. To meet nutrient needs within calorie limits, choose a variety of nutrient-dense foods across and within all food groups in recommended amounts. Cut back on foods and beverages higher in these components to amounts that ft within healthy eating patterns. Consider cultural and personal preferences to make these shifts easier to accomplish and maintain. Everyone has a role in helping to create and support healthy eating patterns in multiple settings nationwide, from home to school to work to communities. Page xii 2015-2020 Dietary Guidelines for Americans Key Recommendations provide further guidance on how individuals can follow the fve Guidelines. The Dietary Guidelines? Key Recommendations for healthy eating patterns should be applied in their entirety, given the interconnected relationship that each dietary component can have with others. Key Recommendations: Consume a healthy eating pattern that accounts for all foods and beverages within an appropriate calorie level. A healthy eating pattern includes:[1] A variety of vegetables from all of the subgroups?dark green, red and orange, legumes (beans and peas), starchy, and other Fruits, especially whole fruits Grains, at least half of which are whole grains Fat-free or low-fat dairy, including milk, yogurt, cheese, and/or fortifed soy beverages A variety of protein foods, including seafood, lean meats and poultry, eggs, legumes (beans and peas), and nuts, seeds, and soy products Oils A healthy eating pattern limits: Saturated fats and trans fats, added sugars, and sodium Key Recommendations that are quantitative are provided for several components of the diet that should be limited. These components are of particular public health concern in the United States, and the specifed limits can help individuals achieve healthy eating patterns within calorie limits: Consume less than 10 percent of calories per day from added sugars[2] Consume less than 10 percent of calories per day from saturated fats[3] Consume less than 2,300 milligrams (mg) per day of sodium[4] If alcohol is consumed, it should be consumed in moderation?up to one drink per day for women and up to two drinks per day for men?and only by adults of legal drinking age. The relationship between diet and physical activity contributes to calorie balance and managing body weight. As such, the Dietary Guidelines includes a Key Recommendation to: Meet the Physical Activity Guidelines for Americans. For most calorie levels, there are not enough calories available after meeting food group needs to consume 10 percent of calories from added sugars and 10 percent of calories from saturated fats and still stay within calorie limits. Nutrient Dense?A characteristic of foods and beverages that provide vitamins, minerals, and other substances that contribute to adequate nutrient intakes or may have positive health effects, with little or no solid fats and added sugars, refned starches, and sodium. Variety?A diverse assortment of foods and beverages across and within all food groups and subgroups selected to fulfll the recommended amounts without exceeding the limits for calories and other dietary components. This edition which they live, work, and shop; and Guidelines is that nutritional needs should of the Dietary Guidelines focuses other contextual factors strongly infuence be met primarily from foods. Concerted efforts among foods, including fresh, canned, dried, and make substitutions?that is, choosing health professionals, communities, frozen, can be included in healthy eating nutrient-dense foods and beverages in businesses and industries, organizations, patterns. Foods in nutrient-dense forms place of less healthy choices?rather governments, and other segments of contain essential vitamins and minerals than increasing intake overall. Most society are needed to support individuals and also dietary fber and other naturally individuals would beneft from shifting and families in making dietary and occurring substances that may have food choices both within and across food physical activity choices that align with positive health effects. Everyone has a fortifed foods and dietary supplements and can be accomplished by making role, and these efforts, in combination may be useful in providing one or more simple substitutions, while others will and over time, have the potential to nutrients that otherwise may be consumed require greater effort to accomplish. Check out the 5 Guidelines that encourage healthy eating patterns: Follow a healthy eating pattern over time to help support a healthy body weight and reduce the risk of chronic disease. Choose a healthy eating pattern at an appropriate calorie level to help achieve and maintain a healthy A Healthy Eating Pattern Limits: body weight, support nutrient adequacy, and reduce the risk of chronic disease. Saturated Fats Added Sugars Sodium & Trans Fats Choose a variety of nutrient-dense foods from each food group in recommended amounts. To meet nutrient needs within Vegetables calorie limits, choose Lettuce Whole-Grain & Celery Bread a variety of nutrient dense foods across and Fruits Dairy within all food groups in Apples Fat-Free Milk recommended amounts. To build a healthy eating pattern, combine healthy choices from across all food groups?while paying attention to calorie limits, too. Check out the 5 Guidelines that encourage healthy eating patterns: Consume an eating pattern low in added sugars, saturated fats, and sodium. Saturated Fats Consume an eating pattern low in added sugars, saturated fats, and sodium. Cut Added Sodium back on foods and Sugars beverages higher in these components to amounts that ft within healthy eating patterns. Choose nutrient-dense foods and beverages across and within all food groups in place of less healthy choices. Shift Consider cultural and personal preferences to make these shifts easier to accomplish Meal A Meal B and maintain. Page xvi? 2015-2020 Dietary Guidelines for Americans Everyone has a role in helping to create and support healthy eating patterns in places where we learn, work, live, and play. More than two-thirds Its goal is to make recommendations of adults and nearly one-third of children Over the past century, essential nutrient about the components of a healthy and youth are overweight or obese.

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In a child with severe haemophilia, these might become serious and should be checked by a haemophilia specialist. Painful swelling or reluctance to use an arm or a leg can be a sign that a bleed has taken place. The specialist nurses and physiotherapists at the Haemophilia Centre can advise on haemophilia issues during these normal childhood stages. Informing the nurse or doctor giving the immunisation that the baby or toddler has haemophilia is important. Injections can be given subcutaneously, into the fatty tissue under the skin, rather than into the muscle, and pressure put on the skin where the child was injected. However, changing the way of giving immunisations isn?t necessary for all children with haemophilia. If you have a child with haemophilia, contact the Haemophilia Centre for advice on how your child should be immunised. Even before pain or swelling becomes obvious they may recognize a ?funny feeling? which is one of the earliest signs of a joint bleed. If they have mild haemophilia, minor injuries may heal normally because there is enough clotting factor activity in the blood. The bleeding problem might not be noticed until the person has surgery, a tooth taken out or a major accident or injury. Growing up with haemophilia With treatment and support from their Haemophilia Centre, most people with haemophilia can live relatively normal healthy lives. Unless there are complications, young people can expect to grow up with fewer or no joint problems from their haemophilia. With sensible precautions, they can play most sports, exercise and look forward to a full and productive life. Men with haemophilia will pass the altered gene on to their daughters but not their sons. Males have one X chromosome, which they receive from their mother, and one Y chromosome, which they receive from their father. There are four possible combinations of sex chromosomes that children can receive from their parents. His sons will not have haemophilia as his ?normal? Y chromosome is passed on to them and they receive their X chromosome from their mother. Women can carry the genetic alteration causing haemophilia even if they don?t have symptoms. A woman who carries the altered gene can pass it on to both her sons and her daughters. With each pregnancy, there is a 50% chance her male baby will have haemophilia or a 50% chance her female baby will carry the altered gene. No family history of haemophilia In about one third of people born with haemophilia, there is no history of the disorder in the family. Once haemophilia appears in a family the altered gene is then passed on from parents to children following the usual pattern for haemophilia. Family members should seek genetic counselling and testing if there is someone in the family who has haemophilia. If their factor levels fall in the range for mild haemophilia (5 40% of normal clotting factor), they may sometimes also be referred to as having ?mild haemophilia. In very rare cases, some girls or women have particularly low factor levels causing them to have moderate or severe haemophilia. Examples of having a bleeding tendency may include: Bruising easily Heavy menstrual bleeding. This may lead to low iron levels or anaemia Excessive bleeding after dental surgery or extractions, other surgery and medical procedures, injuries or accidents Prolonged bleeding after childbirth Females with very low clotting factor levels may also have joint or muscle bleeds. Unlike males with haemophilia, where the factor level is the same within the same family, the factor level in females who carry the gene is unpredictable and varies between family members. Women and girls with lower levels should have theirs checked periodically, as their factor levels may change with age, pregnancy and hormonal medications. If their factor level is low, they will need a treatment plan to prevent bleeding problems and manage any situations that occur. A common time for testing whether a girl or woman carries the gene is when she reaches childbearing age and can understand the process and implications fully and make the decision for herself. Finding out whether she carries the gene is a process which will take time, sometimes many months. The Haemophilia Centre can help with information and advice about genetic testing and can provide a referral to a genetic counsellor, if needed. Women, their partner, parents or family can talk to the Haemophilia Centre or genetic counsellor individually or together prior to testing and many fnd it helpful. If a person starts exploring genetic testing but decides against it, there is no obligation to complete the process. For more information about genetic testing, see the Policies and Position Statements on the Human Genetics Society of Australasia web site Treatment for haemophilia has improved a great deal over the years and it can be valuable to learn more about how haemophilia is treated now and to speak to other people with haemophilia or parents of children with haemophilia or the Haemophilia Centre to see how things have changed. The Haemophilia Centre can also give a referral to a genetic counselling service that specialises in bleeding disorders. Pregnancy and childbirth With good management, women who carry the altered gene causing haemophilia have no more problems with delivering a healthy baby than other mothers. This involves: Ideally, if planning a pregnancy, discussing this with a haemophilia specialist who may refer to a genetic counsellor When the pregnancy is confrmed, contacting the Haemophilia Centre for advice on local obstetric services with experience of haemophilia Asking the haemophilia and obstetrics teams to consult with each other to plan for a smooth and safe pregnancy and delivery and care for the newborn 11 Checking with the Haemophilia Centre before having any invasive procedures, such as chorionic villus sampling or amniocentesis Discussing suitable choices for anaesthesia, especially an epidural, with the Haemophilia Centre and obstetrics teams. A normal vaginal delivery is usually recommended unless there are obstetric complications. Identifying the sex of the baby If a pregnant woman knows she carries the altered gene causing haemophilia, it is advisable to determine the sex of the baby before birth, preferably with a non-invasive test with minimal risk to the foetus, such as ultrasound. The woman and her partner can choose if they want to be told the sex of the baby or not before delivery even if the haemophilia and obstetric teams are aware. If neither the couple nor the medical staff know the sex of the baby and no other genetic testing of the foetus has been carried out, the pregnancy and birth will be managed as if the baby is a male with haemophilia to ensure the baby is delivered safely. Testing for haemophilia before birth For a woman or couples who wish to test for haemophilia before birth, there are two main testing options: Prenatal diagnostic testing: a test during the pregnancy to check the sex of the baby. For these options to be available the gene alteration in the family must be known. There may also be substantial costs involved for these tests and procedures and it may be valuable to clarify this and options for support beforehand. If a pregnant woman has a history of haemophilia in the family and does not know whether she carries the gene, it is important to let the obstetrics team know so that they can plan a safe delivery of the baby with the haemophilia team. This is made by genetic engineering and contains little or no material from human blood or animals. There are several brands available manufactured by different pharmaceutical companies. Clotting factor concentrate can be given: ?On demand? before surgery, childbirth or dental treatment, or after an injury or accident, or once a bleed has started. Factor concentrates are infused (injected) into a vein at home by parents trained to treat their child, or by people themselves when they are confdent enough to do it, or at the Haemophilia Centre. It is used for treating some people with mild haemophilia A and some women with bleeding disorder symptoms. It can help to treat mouth or nosebleeds, gut bleeding or bleeding after dental work. Hormone treatment, such as oral contraceptives (birth control pills), can help women who have heavy menstrual bleeding. Inhibitors After treatment with a clotting factor product, some people with haemophilia may develop antibodies known as ?inhibitors? which make treatment less effective. There are a number of ways to treat inhibitors and many people are successful in overcoming them while others have ongoing problems. Current treatment for people with moderate or severe haemophilia aims to prevent bleeding, pain and joint damage. Many children and young people have benefted from prophylaxis, which reduces the risk of developing the arthritis and joint problems often experienced by those older people who grew up without adequate treatment due to limited product. This helps to prevent bleeds and protect joints as well as maintaining a healthy body and mind. Even when treating with factor replacement regularly, bleeding into joints and muscles may still occur. Most people with haemophilia will need treatment for injuries apart from minor cuts and scratches or in preparation for surgical and some dental procedures.

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Urobilinogen is a colorless product, a small fraction of which is absorbed into the portal blood. Most of it is cleared by the liver, but a minor part reaches the systemic circulation and can be excreted by the kidneys. Measurement of urobilinogen in urine has been used to differentiate between different forms of icterus and cholestasis. However, due to many physiologic variations and technical errors, this parameter has no clinical value. Bilirubin is cleared from the blood, conjugated, and excreted into bile by the liver. The clearance is not an efficient process18,19 in contrast to the hepatic clearance of bile acids. Whereas bile acids are nearly completely cleared during the first passage, bilirubin requires many passages to become cleared completely (Fig. As a conse quence, bilirubin is equally distributed over the entire circulation, but bile acids are highly concentrated in the portal blood and have a low concentration in the systemic circulation. This explains the differences in the reaction pattern of bilirubin and bile Clinical Syndromes Associated with Liver Disease 423 Ineffective clearance and recirculation Complete clearance bilirubin in 1 circulation Bile acids gut Fig. Bile acids are reabsorbed and undergo an enterohepatic circulation, which is maintained by an efficient clearance of bile acids from the portal vein. Bilirubin is not absorbed from the small intestines and its hepatic clearance from the blood has low efficiency. Consequently, there is a high gradient between the portal and systemic concentrations of bile acids, but not of bilirubin. Furthermore, systemic bile acids are increased due to portosystemic shunting and cholestasis; bilirubin is only increased due to cholestasis (or increased production in case of severe hemolysis). In diseases with cholestasis, all bile components including bilirubin and bile acids gain entry to the systemic circulation with the hepatic lymph. This process is not related to hepatic clearance or portal perfusion of the liver. Conversely, in diseases characterized by portosystemic shunting (congenital porto systemic shunts, portal hypertension, acquired collateral circulation, and so forth), the high portal bile acid concentration reaches the systemic circulation giving a high plasma bile acid concentration. However, the bilirubin concentration is not influenced by abnormal liver perfusion. The main processes by which plasma bilirubin may increase are increased produc tion and cholestasis. An increased level becomes clinically visible only as icterus (yellow discoloration of sclerae, mucous membranes and skin) when the concentration exceeds 15 mmol/L. Due to the huge liver reserve capacity, most patients remain in the subclinical region and do not become icteric, despite the fact that nearly all nonvascular liver diseases leadto somedegreeofcholestasis. Given the 2 main reasons for hyperbilirubinemia, increased production and chole stasis, measurement of unconjugated and conjugated bilirubin has been used as an expression of these 2 processes. However, with sensitive techniques, it has been shown that hemolytic (increased production) and hepatobiliary diseases (cholestasis) are not different with respect to the fraction of unconjugated bilirubin, which always 424 Rothuizen varies between 15% and 40%. In liver diseases, there is considerable hemolysis (eg, due to portal hypertension causing reduced splanchnic blood flow with prolonged trapping and degradation of red blood cells in the spleen, and altered erythrocyte membrane fluidity caused by high plasma bile acid concentrations). Furthermore, animals with liver disease may have increased bilirubin production from hepatocyte hemoproteins. Hepatic and hemolytic diseases also have comparable reductions of the bile flow as an expression of cholestasis. With mild anemia, the liver is not damaged and the reserve capacity of the liver prevents such patients from becoming icteric. As hepatic and hemolytic jaundice always consist of a mixed type of hyperbilirubinemia, the measurement of unconjugated and conjugated bilirubin is clinically useless. Furthermore, if only severe hemolysis leads to jaundice, such animals should have pale mucous membranes (and hematocrit <20%). Moderately pale or normally colored mucous membranes in the presence of icterus immediately indicate the presence of a primary disease of the liver or biliary tract. Conjugated bilirubin in plasma binds covalently (irreversibly) to protein albumin. This bilirubin can only escape the circulation when albumin becomes catabolized; its half-life is about 2 weeks. Therefore, after complete recovery from the underlying cholestatic disease, icterus may remain for several weeks and does not necessarily reflect the actual situ ation, which may be important when evaluating the effect of therapy. Portal hypertension can be caused by an increased delivery of blood to the portal system, or by an increased resistance to the passage of portal blood. An increased delivery of blood occurs animals with arteriovenous shunts in the splanchnic circulation, usually in the liver, causing the direct connection of the arterial blood pressure with the portal system. Usually, however, portal hypertension is caused by an increased resistance to the portal blood stream. The cause can be prehepatic (in the portal vein itself), intrahepatic, or posthepatic (hepatic veins, caudal vena cava, heart). Posthepatic causes have little influence on the liver functions, but increased hydrostatic portal blood pressure may cause ascites. Most cases of clinically relevant portal hypertension have a cause inside the liver. Liver diseases causing portal hypertension give rise to different liver Clinical Syndromes Associated with Liver Disease 425 dysfunctions, such as reduced protein and albumin production. However, even in severe liver dysfunction, the capacity of the liver to produce proteins is only moder ately affected due to the large plasticity of the liver. Therefore, albumin levels usually do not fall below 18 to 20 g/L, which is more than the concentration that, by itself, may cause edema and ascites (<15 g/L). However, the combination of portal hypertension and moderate hypoalbuminemia often produces ascites in such animals. The hindrance to the portal circulation develops by way of compression of the portal veins in the portal and periportal area of the liver lobules. Because the cause lies at the site of entry of blood into the liver lobules, the liver itself is not congested. Due to loss of functional tissue, most of these diseases are associated with an abnormally small liver. The most frequent cause of portal vein compression is deposition of collagen (fibrosis)23,24 and infiltration of inflammatory cells (chronic hepatitis). In advanced cases, cirrhosis, defined as disruption of the normal lobular architecture of the liver by fibrous tissue, occurs. Then, resistance to the portal blood flow occurs at different levels of the lobule and is most severe. The other most frequent cause of portal hyper tension is portal vein hypoplasia,25?27 a congenital disease in which the peripheral portal vein branches have not been formed or are incomplete, making the portal system a dead end. Portal vein hypoplasia (formerly called microvascular dysplasia) is associated with variable degrees of liver fibrosis, which may increase the resistance to normal liver perfusion. Posthepatic causes of portal hypertension may be localized in the inferior vena cava and the heart. Obstruction of the hepatic veins either intra or extrahepatic (Budd Chiari syndrome and veno-occlusive disease, respectively) occur in other species, but not in cats or dogs. Thrombosis of the inferior vena cava is rare, and is often caused by an adrenal tumor giving local thrombophlebitis. Such a thrombus grows out in the direc tion of the blood stream and may occlude the lumen over a long distance. In posthe patic causes of portal hypertension the liver is congested and enlarged. Liver functions, however, remain adequate and biochemical examination usually reveals no or only slight liver cell damage and dysfunction. If disorders affecting the afferent portal system cause reduced perfusion of the liver, there is secondary hypoplasia of the portal veins and increased growth of tortuous hepatic arteries (arterialization) in the portal areas. With the exception of congenital shunts, all of these diseases cause increased resistance for the portal blood flow through the liver, and therefore portal hypertension. In posthepatic causes of portal hypertension, the central vein branches may be dis tended and the liver cells in zone 3 degenerated. In chronic cases, fibrous tissue develops around the terminal veins and hepatocyte hyperplasia may occur in zone 1 (periportally).


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