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Patients may complain r Imatinib buy discount super levitra 80 mg online, a competitive inhibitor of the Bcr-Abl ty- of pruritus especially after a hot bath or shower discount super levitra 80mg line. Hy- rosine kinase buy super levitra 80 mg, is recommended for Philadelphia- perviscosity may result in headache or blurred vision order super levitra 80mg with visa. Abnormalities in platelet function can lead to epis- taxis, bruising and mucosal bleeding (including pep- tic ulcer disease) although severe bleeding is unusual. Prevalence r Increased blood cell turnover can lead to hyper- 2per 1,000,000 population. Investigations Fullbloodcountshowsanincreasedredbloodcellcount, Sex haemoglobin and packed cell volume. Polycythaemia vera can be distinguished from other Aetiology causes of polycythaemia by an increase in white cell Increased risk following exposure to benzene or radi- count, platelets and a high neutrophil alkaline phos- ation. On examina- hydroxyurea has been considered safe for long-term tion there is massive splenomegaly. Symptoms and signs maintenance it is also associated with increased risk of marrow failure (anaemia, recurrent infections and of development of leukaemia in comparison with ve- bleeding) may be present. Amyeloproliferative disorder characterised by increased platelets due to clonal proliferation of megakaryocytes Age in the bone marrow. Pathophysiology Platelets although increased in number have disrupted Sex function causing them to clump intravascularly lead- M = F ing to thrombosis, and to fail to aggregate causing bleeding. Risk factors include exposure to excessive ra- bleeding and cerebrovascular symptoms. Pathophysiology In acute leukaemias there is replacement of the normal Investigations bone marrow progenitor cells by blast cells, resulting in The blood lm shows increased numbers of platelets and marrow failure. Bone marrow aspiration demonstrates from the lymphoid side of the haemopoetic system (see increased megakaryocytes. Patients with life-threatening haem- orrhagic or thrombotic events should be treated with Clinical features thrombocytopheresis in addition to hydroxyurea. An- Often there is an insidious onset of anorexia, malaise grelide is occasionally used. There is often a history of recurrent infections and/or easy bruising and mucosal Prognosis bleeding. Other presentations include lymph node en- Essential thrombocythaemia may eventually transform largement, bone and joint pain and symptoms of raised to myelobrosis or acute leukaemia but the disease may intra cranial pressure. Phase 2 involves in- travenous chemotherapy (cyclophosphamide and cy- tosine) with oral 6-mercaptopurine. Lymphoid Stem Cell r Intensication: This involves intravenous metho- trexate and folinic acid, with intramuscular L- asparginase. Lymphoblast r Consolidation: This involves several cycles of chemotherapy at lower doses. Supportive treatment: Cytotoxic therapy and the leukaemia itself depresses normal bone marrow func- T Cell B Cell tion and causes a pancytopenia with resulting infection, anaemia and bleeding. Microscopy Prognosis The normal marrow is replaced by abnormal Prognosisisrelatedtoage,subtypeandinverselypropor- monotonous leukaemic cells of the lymphoid cell line. Over90%ofchildren The leukaemia is typed by cytochemical staining and respond to treatment, the rarer cases occurring in adults monoclonal antibodies to look for cell surface mark- carry a worse prognosis. Full Most common in the middle aged and elderly blood count shows a low haemoglobin, variable white count,lowplateletcount. Bonemarrowaspirationshows Sex increased cellularity with a high percentage of blast cells. On examination there Proerythroblast Myeloid Stem cell Megakaryoblast may be pallor, bruising, hepatosplenomegaly and lym- phadenopathy. Myeloblast Erythrocyte Platelet Microscopy Monoblast Promyelocyte Abnormal leukaemic cells of the myeloid cell line replace the normal marrow. Monocyte Myelocyte The leukaemia is typed by cytochemical staining and Granulocyte monoclonal antibodies to look for cell surface markers. Full blood count shows a low haemoglobin, variable white count, M2 Myelocytic leukaemia with differentiation low platelet count. Bone marrow aspiration shows in- M3 Acute promyelocytic leukaemia creased cellularity with a high percentage of the abnor- M4 Acute myelomonocytic leukaemia mal cells. Bone marrow cytogentic studies allow classi- M5 Acute monocytic leukaemia proliferation of mono- cation into prognostic groups (e. Supportive treatments in- particularly prone to disseminated intravascular co- clude red blood cell transfusions, platelet transfusions agulation due to the presence of procoagulants within and broad-spectrum antibiotics. Ninety-ve 70% of those under 60 years will achieve remission with percent of patients with M3 are induced into remis- combination chemotherapy although the majority re- sion by treatment with high dose retinoic acid. Gum Chronic lymphocytic leukaemia hypertrophy and hepatosplenomegaly is common Denition within this subgroup. Clinical features Often there is an insidious onset of anorexia, malaise Incidence and lethargy due to anaemia. M > F Age Pathophysiology Bimodal distribution with a peak in young adults (1534 Although there is a proliferation in B cells they have years) and older individuals (>55). On Aetiology examination there may be lymphadenopathy and hep- Infectious agents particularly Epstein Barr virus have atosplenomegaly. Involvement with intermittent chemotherapy such as chlorambucil of mediastinal lymph nodes may cause cough, shortness or udarabine. B symptoms may be present (fever >38C, drenching night sweats, weight loss of Prognosis more than 10% within 6 months). The staging of Hodgkinss disease is accord- ing to the Ann Arbor system, which is sufxed by B if Chronic myelogenous Leukaemia Bsymptoms are present and A if they are absent (see See Myeloproliferative disorders page 482. Microscopy Non-Hodgkins lymphoma Classical Reed-Sternberg cells are large cells with a pale cytoplasm and two nuclei with prominent nucleoli said Denition to resemble owl eyes. Incidence r Mixedcellularity disease which mainly affects older 20 per 100,000 per year. Tumours arise due therapy or a combination depending on the stage of to multiple genetic lesions affecting proto-oncogenes Table12. Clinical features r Indolent: Most patients present with painless slowly Prognosis progressive lymphadenopathy. Lymph nodes may re- Indolent lymphomas have a predicted median survival duce in size spontaneously making it difcult to dis- time of 510 years. B symp- sponsive to chemotherapy but have a predicted median toms (fever >38 C, drenching night sweats, weight survival 25 years. On Paraproteinaemias examination there is lymphadenopathy and hep- atosplenomegaly. The cells are trophic to the skin particularly the hands and feet, and result Age in plaques and lumps of associated with generalised Most commonly diagnosed 6065 years. Gas- trointestinallymphomaisparticularlycommoninthe Pathophysiology MiddleEastandisalsoseeninassociationwithcoeliac There is expansion of a single clone of plasma cells that disease. Cleavage of these immunoglobulins tribution according to the Ann Arbor system, which result in the production of Fab and Fc fragments; the Fab is sufxed by B if B symptoms are present (see fragment is termed the Bence-Jones protein and is found Table 12. Investigations There is also production of osteoclast stimulation fac- Thediagnosisismadebylymphnodebiopsy,cytogenetic tor causing lytic bone lesions, bone pain and hypercal- studies of lymphoma cells may give prognostic informa- caemia. Spinal cord compression occurs in approx- imately 1020% of patients at some time during Pathophysiology the course of disease. Hypercalcaemia causes thirst, The abnormal proliferation of lymphoplasmacytoid polyuria, constipation and abdominal pain. Investigations The diagnosis of myeloma is made if there are: Clinical features r Bone marrow aspirate has at least 1015% plasma Hyperviscosity presents as weakness, tiredness, confu- cells. Patients also often have peripheral lymphadenopa- Other investigations include: thy. Chemotherapy with single alkylating agents improves r Protein electrophoresis shows an IgM parapro- prognosis. Recently, thalidomide has been demonstrated to produce a signicant response Management in 30% of patients whose disease progressed following Chemotherapy produces a variable response. Supportive care includes blood transfu- pheresis is used for symptomatic hyperviscosity. Investigations Sex Electropheresis of serum protein demonstrates a raised X linked; males only affected. Aetiology Mutations on the X chromosome including deletions, Management frame shifts and insertions. One third of cases are new Aproportionofpatients will go on to develop multi- mutations. Clinical features Type 1 and 2 causes mild disease with bleeding following Investigations injury, menorrhagia and epistaxis.

When the wings are decelerated toward the end of the stroke generic super levitra 80mg line, this energy must be dissipated buy cheapest super levitra. During the downstroke order super levitra from india, the kinetic energy is dissipated by the muscles themselves and is converted into heat buy 80mg super levitra. The wing joints of these insects contain a pad of elastic, rubberlike protein called resilin (Fig. The kinetic energy of the wing is converted into potential energy in the stretched resilin, which stores the energy much like a spring. Using a few simplifying assumptions, we can calculate the amount of energy stored in the stretched resilin. Although the resilin is bent into a com- plex shape, we will assume in our calculation that it is a straight rod of area A and length. Furthermore, we will assume that throughout the stretch the resilin obeys Hookes law. This is not strictly true as the resilin is stretched by a considerable amount and therefore both the area and Youngs modulus change in the process of stretching. Typically, in an insect the size of a bee the volume of the resilin may be equivalent to a cylinder 2 102 cm long and 4 104 cm2 in area. We will assume that the length of the resilin rod is increased by 50% when stretched. Experiments show that as much as 80% of the kinetic energy of the wing may be stored in the resilin. The hind legs of the ea, for exam- ple, also contain resilin, which stores energy for jumping (see Exercise 6-3). Compute the force on the body of the insect that must be generated during the downward wing stroke to keep the insect hovering. Referring to the discussion in the text, compute the point of attachment to the wing of muscle B in Fig. Assume that the shape of the resilin in each leg of the ea is equivalent to a cylinder 2 102 cm long and 104 cm2 in area. If the change in the length of the resilin is 102 cm, calculate the energy stored in the resilin. How large would these pads have to be in order for them to store 1 enough energy for a m jump? In the next three chapters, we will discuss the behavior of liquids and gases, both of which play an important role in the life sci- ences. The dierences in the physical properties of solids, liquids, and gases are explained in terms of the forces that bind the molecules. In a solid, the molecules are rigidly bound; a solid therefore has a denite shape and vol- ume. The molecules constituting a liquid are not bound together with su- cient force to maintain a denite shape, but the binding is suciently strong to maintain a denite volume. Therefore a gas has neither a denite shape nor a denite volumeit completely lls the vessel in which it is contained. Fluids and solids are governed by the same laws of mechan- ics, but, because of their ability to ow, uids exhibit some phenomena not found in solid matter. In this chapter we will illustrate the properties of uid pressure, buoyant force in liquids, and surface tension with examples from biology and zoology. When a force is applied to one section of a solid, this force is transmitted to the other parts of the solid with its direction unchanged. Because of a uids ability to ow, it transmits a force uniformly in all directions. A uid in a container exerts a force on all parts of the container in contact with the uid. The pressure in a uid increases with depth because of the weight of the uid above. In a uid of constant density, the dierence in pressure, P2 P1, between two points separated by a vertical distance h is P2 P1 gh (7. The relationship between the torr and several of the other units used to measure pressure follows: 1 torr 1mmHg 13. Because the pressure throughout the uid is the same, the force F2 acting on the area A2 in Fig. There are, however, soft-bodied animals (such as the sea anemone and the earthworm) that lack a rm skeleton. For the purpose of understanding the movements of an animal such as a worm, we can think of the animal as consisting of a closed elastic cylinder lled with a liquid; the cylinder is its hydrostatic skeleton. The worm pro- duces its movements with the longitudinal and circular muscles running along the walls of the cylinder (see Fig. Because the volume of the liquid in the cylinder is constant, contraction of the circular muscles makes the worm thinner and longer. Contraction of the longitudinal muscles causes the animal to become shorter and fatter. If the longitudinal muscles contract only on one side, the animal bends toward the contracting side. By anchoring alternate ends of its body to a surface and by producing sequential longitudinal and cir- cular contractions, the animal moves itself forward or backward. Assume that the circular muscles running around its circumference are uniformly distributed along the length of the worm and that the eective area of the muscle per unit length of the worm Section 7. The force Ff in the forward direction generated by this pressure, which stretches the worm, is 2 4 Ff P r 1. We will now use Archimedes principle to calculate the power required to remain aoat in water and to study the buoyancy of sh. If its density is greater than that of water, the animal must perform work in order not to sink. We will calculate the power P required for an animal of volume V and density to oat with a fraction f of its volume submerged. This motion accelerates the water downward and results in the upward reaction force that supports the animal. If the area of the moving limbs is A and the nal velocity of the accelerated water is v, the mass of water accelerated per unit time in the treading motion is given by (see Exercise 7-1) m Avw (7. The force producing this change in the momentum is applied to the water by the moving limbs. The kinetic energy given to the water each second is half the product of the mass accelerated each second and the squared nal velocity of the water. Note that, in our calculation, we have neglected the kinetic energy of the moving limbs. We can nd the percentage of the body volume X occupied by the porous bone that makes the average density of the sh be the same as the density of sea water (1. In sh that possess swim bladders, the decrease in density is provided by the gas in the bladder. Because the density of the gas is negligible compared to the density of tissue, the volume of the swim bladder required to reduce the density of the sh is smaller than that of the porous bone. For exam- ple, to achieve the density reduction calculated in the preceding example, the volume of the bladder is only about 4% of the total volume of the sh (see Exercise 7-6). The cuttlesh alters its density by injecting or withdrawing uid from its porous bone. Fish with swim bladders alter their density by changing the amount of gas in the bladder. A molecule in the interior of the liquid is surrounded by an equal number of neighboring molecules in all directions. Therefore, the net resultant inter- molecular force on an interior molecule is zero. Because there are no molecules above the surface, a molecule here is pulled predominantly in one direction, toward the interior of the surface. This causes the surface of a liquid to con- tract and behave somewhat like a stretched membrane. This contracting ten- dency results in a surface tension that resists an increase in the free surface of the liquid. It can be shown (see reference [7-7]) that surface tension is a force acting tangential to the surface, normal to a line of unit length on the surface (Fig. At the same time, however, these molecules are also subject to the attractive cohesive force exerted by the liquid, which pulls the molecules in the opposite direction.

You survived called plasma that contains clotting proteins discount super levitra 80 mg visa, the scrape just ne because blood contains electrolytes buy discount super levitra 80 mg on line, and many other important molecules order super levitra 80 mg overnight delivery. Skin plays an important role in preserving steps in the immediate care of a burn patient uid balance and in regulating body temperature took scientists decades to gure out cheap super levitra 80mg line, as they and sensation. Immune cells in skin help the body performed carefully conducted experiments on prevent and ght disease. Burn-induced 1980s, researchers doing this work developed skin loss can give bacteria and other microorgan the rst version of an articial skin covering called isms easy access to the nutrient-rich uids that Integra Dermal Regeneration Template, which course through the body, while at the same time doctors use to drape over the area where the allowing these uids to leak out rapidly. Today, Integra uid loss can thrust a burn or trauma patient into Dermal Regeneration Template is used to treat shock, so doctors must replenish skin lost to severe burn patients throughout the world. Two organ quick way to get a needed medicine to a diseased systems are particularly interesting to pharma organ, one of the biggest problems is getting the cologists: the nervous system (which transmits medicine to the correct organ. In many cases, electrical signals over wide distances) and the drugs end up where they are not needed and cause endocrine system (which communicates messages side effects, as weve already noted. These two systems are drugs may encounter many different obstacles key targets for medicines. Some medicines get lost when they stick tightly to certain proteins in the blood, effectively putting the drugs out of business. Skin consists of three layers, making up a dynamic network of cells, nerves, and blood vessels. Blood Vessel Nerve Hair Follicle Sweat Gland Fat 20 National Institute of General Medical Sciences No Pain, Your Gain Like curares effects on acetylcholine, the inter actions between another drugaspirinand metabolism shed light on how the body works. This little white pill has been one of the most widely used drugs in history, and many say that it launched the entire pharmaceutical industry. The bark of the willow tree contains a substance called salicin, a known antidote to headache and fever since the time of the Greek physician Hippocrates, around 400 B. Despite its usefulness dating back to ancient times, early records indicate that salicylate wreaked havoc on the stomachs of people who ingested this natural chemical. In the late 1800s, a scientic Salicylate Acetylsalicylate is the aspirin of today. Adding a chemical tag called an acetyl group (shaded yellow box, right) to a molecule derived from willow bark (salicy late, above) makes the molecule less acidic (and easier on the lining of the digestive tract), but still effective at relieving pain. Acetylsalicylate (Aspirin) Medicines By Design I Body, Heal Thyself 21 breakthrough turned willow-derived salicylate into a medicine friendlier to the body. Bayer scientist Felix Hoffman discovered that adding a chemical tag called an acetyl group (see gure, page 20) to salicylate made the molecule less acidic and a little gentler on the stomach, but the chemical change did not seem to lessen the drugs ability to relieve his fathers rheumatism. Aspirin works by blocking the production of messenger molecules called prostaglandins. Because of the many important roles they play in metabolism, prostaglandins are important targets for drugs and are very interesting to pharma cologists. Prostaglandins can help muscles relax and open up blood vessels, they give you a fever when youre infected with bacteria, and they also marshal the immune system by stimulating the process called inammation. Sunburn, bee stings, tendinitis, and arthritis are just a few examples of painful inammation caused by the bodys release of certain types of prostaglandins in response to an injury. These kinds to this large class of medicines include Advil, of experiments teach scientists about molecular Aleve, and many other popular pain relievers function by providing clear pictures of how all the available without a doctors prescription. All these folds and bends of an enzymeusually a protein drugs share aspirins ability to knock back the or group of interacting proteinshelp it do its production of prostaglandins by blocking an job. Antibodies are spectacularly specic pro teins that seek out and mark for destruction anything they do not recognize as belonging to the body. Scientists have learned how to join antibody-making cells with cells that grow and divide continuously. This pro Recently, researchers have also gured out how to tection, however, can run afoul if the body produce monoclonal antibodies in the egg whites slips up and views its own tissue as foreign. This may reduce production costs of Autoimmune disease, in which the immune system these increasingly important drugs. A drug called The powerful immune army presents signi Rituxan was the rst therapeutic antibody cant roadblocks for pharmacologists trying to approved by the Food and Drug Administration create new drugs. Another thera pursuing immunotherapy as a way to treat a peutic antibody for cancer, Herceptin, latches wide range of health problems, especially cancer. Herceptins forms of antibodiesour immune systems actions prevent breast cancer from spreading to front-line agents. Researchers are also investigating a new kind of vaccine as therapy for diseases such as cancer. The vaccines are not designed to prevent cancer, Medicines By Design I Body, Heal Thyself 25 but rather to treat the disease when it has already research will point the way toward getting a taken hold in the body. Unlike the targeted-attack sick body to heal itself, it is likely that there approach of antibody therapy, vaccines aim to will always be a need for medicines to speed recruit the entire immune system to ght off a recovery from the many illnesses that tumor. The body machine has a tremendously com plex collection of chemical signals that are relayed back and forth through the blood and into and out of cells. While scientists are hopeful that future A Shock to the System difculty pumping enough blood, and body temper ature climbs or falls rapidly. Despite the obvious public health importance of nding effective ways to treat sepsis, researchers have been frustratingly unsuccessful. Kevin Tracey of the North Shore-Long Island Jewish Research Institute in Manhasset, New York, has identied an unusual suspect in the deadly crime of sepsis: the nervous system. Tracey and his coworkers have discovered an unexpected link between cytokines, the chemical weapons released by the immune system during sepsis, and a major nerve that con trols critical body functions such as heart rate and digestion. Further serious public health problem, causing more deaths research has led Tracey to conclude that produc annually than heart disease. The most severe form tion of the neurotransmitter acetylcholine underlies of sepsis occurs when bacteria leak into the blood the inammation-blocking response. Tracey is stream, spilling their poisons and leading to a investigating whether stimulating the vagus nerve dangerous condition called septic shock. Blood can be used as a component of therapy for sepsis pressure plunges dangerously low, the heart has and as a treatment for other immune disorders. The clich could not be more apt for biologists trying to understand how a complicated enzyme works. For decades, researchers have isolated and puried individual enzymes from cells, performing experi ments with these proteins to nd out how they do their job of speeding up chemical reac tions. But to thoroughly understand a molecules function, scientists have to take a very, very close look at how all the atoms t together and enable the molecular machine to work properly. Tremors, increased Give two examples of heart rate, and problems with sexual function immunotherapy. Plants have for sure what the earliest humans did to treat also served as the starting point for countless drugs their ailments, but they probably sought cures in on the market today. Drug discovery scientists often refer to these ideas as leads, and chemicals that have desirable properties in lab tests are called lead compounds. Natural Cholesterol-Buster Having high cholesterol is a signicant risk factor and his coworker David Moore of Baylor College for heart disease, a leading cause of death in the of Medicine in Houston, Texas, found that guggul industrialized world. This research, part of which rst identied cholesterol receptors, led to the development of the popular cholesterol-lowering statin drugs such as Mevacor and Lipitor. New research from pharmacologist David Mangelsdorf, also at the University of Texas Southwestern Medical Center at Dallas, is pointing to another potential treatment for high cholesterol. The new substance has the tongue-twisting name guggulsterone, and it isnt really new at all. Guggulsterone comes from the sap of the guggul tree, a species native to India, and has been used in Indias Ayurvedic medicine since at least 600 B. Medicines By Design I Drugs From Nature, Then and Now 29 Relatively speaking, very few species of living only a few of these organisms to see whether they things on Earth have actually been seen and harbor some sort of medically useful substance. Many of these unidentied Pharmaceutical chemists seek ideas for new organisms arent necessarily lurking in uninhab drugs not only in plants, but in any part of nature ited places. This includes identied a brand-new species of millipede in a searching for organisms from what has been called rotting leaf pile in New York Citys Central Park, the last unexplored frontier: the seawater that an area visited by thousands of people every day. Scientists estimate that Earth is home to at least 250,000 different species of plants, and that up to 30 million species of insects crawl or y some where around the globe.

They secrete a substance from their abdomen that reduces the surface tension behind them purchase super levitra 80 mg free shipping. Here the eect is similar to cutting a taut rubber membrane which then draws apart cheap super levitra express, each section moving away from the cut purchase super levitra on line amex. This eect known as Marangoni propulsion can be demonstrated simply by coating one end of a toothpick with soap purchase super levitra uk, and placing it in water. The soap acting as the surfactant reduces the surface tension behind the coated end resulting in the acceleration of the toothpick away from the dissolved soap. Experiments have shown that the surfactant excreted by insects reduces the surface tension of water from 73 dyn/cm to about 50 dyn/cm. Measurements show that during Marangoni propulsion, Microvelia can attain peak speeds of 17 cm/sec. Assume that the average density of the human body is about the same as water ( 1 g/cm3) and that the area A of the limbs w acting on the water is about 600 cm2. If the situation is reversed, the immersed animal tends to rise to the surface, and it must expend energy to keep itself below the surface. Calculate volume of the swim bladder as a percent of the total vol- ume of the sh in order to reduce the average density of the sh from 1. The density of an animal is conveniently obtained by weighing it rst in air and then immersed in a uid. If the density of the uid is 1, the average density 2 of the animal is W1 2 1 W1 W2 Derive this relationship. If a section of coarse-grained soil is adjacent to a ner grained soil of the same material, water will seep from the coarse-grained to the ner grained soil. Calculate the perimeter of a platform required to support a 70 kg person solely by surface tension. Assume that the linear dimension of the insect is 3 101 cm and its mass is 3 102 g. Further, assume that the surface tension dierence between the clean water and surfactant altered water provides the force to accel- erate the insect. Poiseuille (17991869), was a French physician whose study of moving uids was motivated by his interest in the ow of blood through the body. In this chapter, we will review briey the principles governing the ow of uids and then examine the ow of blood in the circulatory system. Bernoullis equation states that at any point in the channel of a owing uid the following relationship holds: 1 2 P + gh + v Constant (8. The rst term in the equation is the potential energy per unit volume of the uid due to the pressure in the uid. Consider a uid owing through a pipe consisting of two segments with cross- sectional areas A1 and A2, respectively (see Fig. The volume of uid owing per second past any point in the pipe is given by the product of the uid velocity and the area of the pipe, A v. If the uid is incompressible, in a unit time as much uid must ow out of the pipe as ows into it. Therefore, the rates of ow in segments 1 and 2 are equal; that is, A1 A1v1 A2v2 or v2 v1 (8. Therefore the relationship between the parameters P,, h, and v at points 1 and 2 is 1 2 1 2 P1 + gh1 + v P2 + gh2 + v (8. Viscous friction is pro- portional to the velocity of ow and to the coecient of viscosity for the given uid. As a result of viscous friction, the velocity of a uid owing through a pipe varies across the pipe. The velocity is highest at the center and decreases toward the walls; at the walls of the pipe, the uid is stationary. The lengths of the arrows are proportional to the velocity across the pipe diameter. If viscosity is taken into account, it can be shown (see reference [8-5]) that the rate of laminar ow Q through a cylindrical tube of radius R and length L is given by Poiseuilles law, which is R4 (P P ) 1 2 3 Q cm /sec (8. In general, viscosity is a function of temperature and increases as the uid becomes colder. This fact is evident from Bernoullis equation, which shows that if the height and velocity of the uid remain constant, there is no pressure drop along the ow path. The product of the pressure drop and the area of the pipe is the force required to overcome the frictional forces that tend to retard the ow in the pipe segment. Note that for a given ow rate the pressure drop required to overcome frictional losses decreases as the fourth power of the pipe radius. Thus, even though all uids are subject to friction, if the area of the ow is large, frictional losses and the accompanying pressure drop are small and can be neglected. The ow becomes turbulent with eddies and whirls disrupting the laminar ow (see Fig. In a cylindrical pipe the critical ow velocity vc above which the ow is turbulent, is given by vc (8. The symbol is the Reynolds number, which for most uids has a value between 2000 and 3000. Therefore, as the ow turns turbulent, it becomes more dicult to force a uid through a pipe. Blood is not a simple uid; it contains cells that complicate the ow, especially when the passages become narrow. Furthermore, the veins and arteries are not rigid pipes but are elastic and alter their shape in response to the forces applied by the uid. Still, it is possible to analyze the circulatory system with reasonable accuracy using the concepts developed for simple uids owing in rigid pipes. The blood in the circulatory system brings oxygen, nutrients, and various other vital substances to the cells and removes the metabolic waste products from the cells. The blood is pumped through the circulatory system by the heart, and it leaves the heart through vessels called arteries and returns to it through veins. The mammalian heart consists of two independent pumps, each made of two chambers called the atrium and the ventricle. The entrances to and exits from these chambers are controlled by valves that are arranged to maintain the ow of blood in the proper direction. Blood from all parts of the body except the lungs enters the right atrium, which contracts and forces the blood into the right ventricle. The ventricle then contracts and drives the blood through the pulmonary artery into the lungs. In its passage through the lungs, the blood releases carbon dioxide and absorbs oxygen. The contraction of the left atrium forces the blood into the left ventricle, which on contraction drives the oxygen-rich blood through the aorta into the arteries that lead to all parts of the body except the lungs. Thus, the right side of the heart pumps the blood through the lungs, and the left side pumps it through the rest of the body. These in turn branch into still smaller arteries, the smallest of which are called arterioles. As we will explain later, the arte- rioles play an important role in regulating the blood ow to specic regions in Section 8. The arterioles branch further into narrow capillaries that are often barely wide enough to allow the passage of single blood cells. The capillaries are so profusely spread through the tissue that nearly all the cells in the body are close to a capillary. The capillaries join into tiny veins called venules, which in turn merge into larger and larger veins that lead the oxygen-depleted blood back to the right atrium of the heart. First the atria contract, forcing the blood into the ventricles; then the ventricles contract, forcing the blood out of the heart. Because of the pumping action of the heart, blood enters the arteries in spurts or pulses. The maximum pressure driving the blood at the peak of the pulse is called the systolic pressure. Ina young healthy individual the systolic pressure is about 120 torr (mm Hg) and the diastolic pressure is about 80 torr. As the blood ows through the circulatory system, its initial energy, pro- vided by the pumping action of the heart, is dissipated by two loss mecha- nisms: losses associated with the expansion and contraction of the arterial walls and viscous friction associated with the blood ow. Due to these energy losses, the initial pressure uctuations are smoothed out as the blood ows away from the heart, and the average pressure drops.

For the point farthest from the line order line super levitra, calculate its deviation from the value on the line order super levitra 80 mg. Calibration of the "sleeves" must be performed each time the dose calibrator is returned from repair 80 mg super levitra mastercard. Geometry Independence Geometry means that the indicated activity does not change with volume or configuration 80 mg super levitra fast delivery. Geometry tests should be completed prior to use after installation or repair of the calibrator. Licensees who use generators and radiopharmaceutical kits should also do the test using a vial similar in size, shape, and construction to the radiopharmaceutical kit vials normally used. The following test assumes injections are done with 3-cc plastic syringes and that the radiopharmaceutical kits are made in 30-cc glass vials. If you do not use these, change the procedure so that your syringes and vials are tested throughout the range of volumes commonly used. For all the other volumes, divide the standard millicuries by the millicuries indicated for each volume correction factor. Alternatively, you may graph the data and draw horizontal five (5) percent error lines above and below the chosen standard volume. This will also be necessary if any data points lie outside the five (5) percent error lines. Be sure to label the table or graph "syringe geometry dependence," and note the date of the test and the model number and serial number of the calibrator. For all the other volumes, divide the standard millicuries by the millicuries indicated for each volume. Be sure to label the table or graph, note the date of the test, and indicate the model number and serial number of the calibrator. Accuracy tests should be completed at installation and at intervals not to exceed 12 months thereafter. The supplier must compare that source to a source that was calibrated by the National Bureau of Standards. Certified sources are available from the National Bureau of Standards and from many radioisotope suppliers. Consider using at least one reference source whose activity is within the range of activities normally assayed. The average value should be within five (5) percent of the certified activity of the reference source, mathematically corrected for decay. State on your application, "We have developed an exposure monitoring program for your review that is appended as Appendix G," and submit your monitoring program. The licensee must control occupational doses and provide individuals with monitoring devices in accordance with the requirements of 4731. Adults likely to receive in one year a dose in excess of 10 percent of those dose limits must be provided with dosimetry. If monitoring is required, each licensee shall maintain records of doses received and individuals must be informed on at least an annual basis of their doses. Providing for the safe use of radioactive materials and radiation is a management responsibility. It is important that management recognize the importance of radiation monitoring in the overall requirements for radiation protection. In evaluating the eye dose equivalent, it is acceptable to take credit for the shielding provided by protective lenses. Monitoring devices are accordingly required for adults with an annual dose in excess of o 0. To demonstrate that monitoring of occupational exposure is not necessary for a group of radiation workers, it must be demonstrated that doses will not exceed 10% of the applicable limits. The following methods may be used to demonstrate that doses are expected to be within 10% of regulatory limits: Prior Experience: Review of radiation dose histories for workers in a specific work area show that they are not likely to receive a dose in excess of 10% of the limits; Area Surveys: Demonstrate through the conduct of appropriate radiation level surveys (e. The device for monitoring the whole body dose, eye dose, skin dose, or extremity dose must be placed near the location expected to receive the highest dose during the year. When the whole body is exposed fairly uniformly, the individual monitoring device is typically worn on the front of the upper torso. For example, if the dose rate to the head is expected to be higher than the dose rate to the trunk of the body, a monitoring device shall be located on or close to the head. The monitoring year may be adjusted as necessary to permit a smooth transition from one monitoring year to another, as long as the year begins and ends in the month of January, the change is made at the beginning of the year, and no day is omitted or duplicated in consecutive years. Because evaluation of dose is an important part of the radiation protection program, it is important that users return dosimeters on time. Delays in processing a dosimeter can result in the loss of the stored information. Sometimes the most reliable method for estimating an individuals dose is to use his/her recent dose history. In other cases, particularly if the individual does non-routine types of work, it may be better to use doses of co-workers as the basis for the dose estimate. Investigational Levels External Dose Monitoring The investigational levels in this program are not new dose limits. When the cumulative annual exposure to a radiation worker exceeds Investigational Level I in the following table (i. The actions listed below should be taken when the investigation levels in Table 1are reached: Personnel dose less than Investigational Level I. Factors that led to the radiation exposure and the radiation doses and work habits of other individuals engaged in similar tasks should be considered to determine if improvements additional safety measures are needed to reduce exposures. The licensee shall make efforts to avoid substantial variation above a uniform monthly exposure rate to a declared pregnant woman. If the pregnancy is declared in writing and includes the workers estimated date of conception, the dose equivalent to an embryo/fetus shall be taken as the sum of: The deep-dose equivalent to the declared pregnant woman; and The dose equivalent to the embryo/fetus from radionuclides in the embryo/fetus and radionuclides in the declared pregnant woman. The total effective dose equivalent concept makes it possible to combine both the internal and external doses in assessing the overall risk to the health of an individual. The types and quantities of radioactive material manipulated at most medical facilities do not provide a reasonable possibility for an internal intake by workers. However, uses such as preparing radioiodine capsules from liquid solutions, and opening and dispensing radioiodine from vials containing millicurie quantities require particular caution. To monitor internal exposures from such operations, a routine bioassay program to periodically monitor workers should be established. If a licensee determines that a program for performing thyroid uptake bioassay measurements is necessary, a program should be established. The program should include: adequate equipment to perform bioassay measurements, procedures for calibrating the equipment, including factors necessary to convert counts per minute into Becquerel or microcurie units, the technical problems commonly associated with performing thyroid bioassays (e. They can also become saturated or be spoiled by improper use, humidity, chemicals, or inadequate maintenance. If there is a significant increase in the measured activity, the trap must be replaced. Type and Location of Use In general, there are two types of mobile medical service. One type is transportation and use of radioactive material within a transport vehicle (e. A second type is transportation of radioactive material to a clients facility for use within a clients facility by the mobile medical services employees (i. Service providers who only transport and store a therapy device need only apply for authorization for possession and transport of the radioactive material. In this case, when the service provider is only transporting the therapy device for use, the client must possess a license for medical use of the radioactive material. Additionally, in this case, the client is authorized to provide the patient treatments and is responsible for all aspects of the radioactive material use and patient treatments upon transfer of the radioactive material to their possession. Licensed activities must be conducted in accordance with the regulations for compliance with 4731. The letter will permit the use of radioactive material at the clients address and will clearly delineate the authority and responsibility of each entity. This agreement must be applicable for the entire period of time over which the service is to be provided.

They should receive close monitoring and specialist care throughout pregnancy and childbirth purchase super levitra 80 mg with visa. Between 2 and 12 percent of women develop gestational diabetes14 buy generic super levitra pills, which is more common in women from minority ethnic groups purchase generic super levitra on line. These women are more likely to have large-for-dates babies cheap super levitra 80 mg otc, a risk that can be reduced by reducing maternal hyperglycaemia. Women whose blood glucose levels revert to normal after delivery have an increased risk of developing Type 2 diabetes later in life. They can reduce this risk by increasing their physical activity levels, eating a balanced diet and avoiding excessive weight gain. The Childrens National Service Framework will set standards for maternity services and will complement the National Service Framework for Diabetes. Key interventions q Tight blood glucose control before and during pregnancy in women with pre- existing diabetes leads to a reduction in congenital malformation rates and perinatal mortality rates. These should cover: q the provision of advice to all women of child-bearing age with diabetes about the importance of good blood glucose control before and during pregnancy q the provision of pre-conception care q the provision of antenatal care, including the detection and management of microvascular complications of diabetes and the detection and management of obstetric complications q the provision of intrapartum and postpartum care q the detection and management of neonatal hypoglycaemia and other neonatal complications in babies born to women with diabetes. Standard 10 All young people and adults with diabetes will receive regular surveillance for the long- term complications of diabetes. Standard 12 All people with diabetes requiring multi-agency support will receive integrated health and social care. People with diabetes are at risk of developing the microvascular complications of diabetes: diabetic retinopathy (damage to the eyes), diabetic nephropathy (damage to the kidneys) and diabetic neuropathy (damage to the nerves). They are also at increased risk of developing cardiovascular disease, including coronary heart disease, stroke and peripheral vascular disease. The impact of the microvascular complications can be reduced if they are detected and treated at an early stage. Early detection of sight-threatening diabetic retinopathy and treatment with laser therapy can prevent visual impairment. The quality of life of those who develop visual impairment can be improved by access to low vision aids, information, psychological support and appropriate welfare benefits. Tight control of raised blood pressure, as well as tight blood glucose control, can significantly reduce the rate of progression of diabetic nephropathy. Diabetic foot problems are the most frequent manifestation of diabetic neuropathy. Foot ulceration and lower limb amputation can be reduced if people who have sensory neuropathy affecting their feet are identified and offered foot care education, podiatry and, where required, protective footwear. People with diabetes who develop cardiovascular disease can benefit from secondary prevention measures already recommended for the general population in the National Service Framework for Coronary Heart Disease, including treatment with low dose aspirin, -blockers and lipid-lowering agents. In addition, outcomes for people with Type 2 diabetes who have a heart attack are improved if they are treated with intensive insulin therapy. The second stage of the National Service Framework for Diabetes: Delivery Strategy, will be published in summer 2002. It will take account of comments received from the consultation on the detailed interventions, service models and performance indicators described on the website. It will set out the action to be taken by local health and social care systems, milestones, performance management arrangements and the underpinning national programmes to support local delivery. The Delivery Strategy will set out actions and milestones required of each level of the service and partner agencies. At the same time, we need to take account of the wider priorities for modernisation. The National Director for Primary Care, David Colin-Thome, is leading a project to look at the implementation of National Service Frameworks so as to manage the pressures on primary care. A proposed set of performance indicators to monitor progress towards the achievement of each standard and proposals for setting up virtual practice-based diabetes registers are on the web www. This will be co-chaired by Professor Mike Pringle (Co-chair of the Diabetes External Reference Group) and Dr Sheila Adam (Director of Policy in the Department of Health). In the meantime, some local services will already have put in place some of the interventions and service models proposed on the web. In addition, there will be a rolling programme to assess specific areas of care, and this will include diabetes. The survey will provide a baseline from which we can trace improvements over time, providing a foundation for local action, based on the views of people with diabetes. This work will be taken forward through the programme on public and patient involvement and The Expert Patient. We are publishing this document now to give local health and social care systems the opportunity to develop thinking on implementing the National Service Framework for Diabetes: Standards in the lead up to April 2003. Where Local Diabetes Services Advisory Groups exist, their work may provide the basis for this. List two causes each for type 1 Type 1 diabetes is one of the most common chronic and type 2 diabetes. The reason for this is the treatment of type 1 and 2 unknown, although it is most likely related to the environment diabetes. The list of famous people: sport stars, politicians, movie stars and artists, who have type 1 or type 2 diabetes is long. Following diagnosis, children frequently discover classmates who also have diabetes. Their looks, personalities and activities are no different from those of anyone else. The rate of development of type 2 diabetes in children has increased in recent years. This is due primarily to eating high calorie and high fat foods as well as a lack of exercise resulting in excess weight gain. Three risk factors seem to be important in determining why a person develops type 1 diabetes: 1. We know this from studies of identical The first important reason seems to be an twins. When one identical twin gets inherited or genetic factor, such as the way a diabetes, only in half of the cases does the person inherits the color of the eyes from a other twin also develop the disease. We dont completely understand the inheritance People with type 1 diabetes are more likely to factors. There can be evidence of this allergic This combination makes a person more reaction found in the blood. This is especially reaction is against the cells in the pancreas true when they have a relative with diabetes. Most Anglo and about half of Hispanic and African- Over half of the families (up to 90 percent American children show this allergy when in one study) have no close relative with they develop diabetes. They are genes that help to protect a person from easier to measure and have also been found developing diabetes. Children from a family who have a child with diabetes have a greater chance of Identifying these antibodies in the blood has developing it than without a family history. The antibodies gradually disappear from the The body would then make islet cell blood after the onset of type 1 diabetes. This environmental factor may either be a virus We now know that most people who get or something in the food we eat or something diabetes dont just suddenly develop it. This factor may be have been in the process of developing it for the bridge between the genetic (inherited) part many years, sometimes even from birth. As more and more islet cells are destroyed A person inherits the tendency for diabetes. It does not just come on suddenly in the week or two before the elevated blood sugars. The insults may include viral infections, stress, chemicals in the diet or other agents. These agents may work by activating white blood cells in the islets to make toxic chemicals that cause injury to the insulin-producing cells (beta cells). However, a genetic-predisposition (inherited factors) must be present for the process to start. They also do contrast, it is not a risk factor for type 1 not make islet cell antibodies. This is similar to what happens if you My daughter was in a car accident are allergic to something that makes you Q the week before the onset of her sneeze.