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Transferrin A plasma β1-globulin responsible for the binding of iron and its transport in the bloodstream cheap flavoxate express spasms during sleep. It catalyzes the formation of isopeptide bonds between glutamine and lysine residues on fibrin purchase 200 mg flavoxate with amex spasms in spanish, forming stable covalent cross-links purchase flavoxate 200 mg skeletal muscle relaxants quiz. Urokinase An enzyme found in urine that activates plasminogen to plasmin and is used as a thrombolytic agent in the treatment of thrombosis. Vasoconstriction Narrowing of the lumen of blood vessels that occurs immediately following an injury. Viscosity Resistance to flow; physical property is dependent on the friction of component molecules in a substance as they pass one another. Von Willebrand disease An autosomal dominant hereditary bleeding disorder in which there is a lack of von Willebrand factor (vWf). The antibody/antigen complex on the cell membrane sensitizes the erythrocyte, which is removed in the spleen or liver. Wedge smear Blood smear prepared on a glass microscope slide by placing a drop of blood at one end and with a second slide pulling the blood the length of the slide. White thrombus Thrombus composed mostly of platelets and fibrin that appears light gray. Zymogen An inactive precursor that can be converted to the active form by an enzyme, alkali, or acid. Protection provided by the cross-placental transfer of antibodies from mother to child is more effective against some infections. How vaccines work Vaccines produce their protective effect by inducing active immunity and providing immunological memory. Immunological memory enables the immune system to recognise and respond rapidly to exposure to natural infection at a later date and thus to prevent or modify the disease. Antibodies can be detected in blood or serum, but, even in the absence of detectable antibodies, immunological memory may still be present. Vaccines can be made from inactivated (killed) or attenuated live organisms, secreted products, recombinant components or the constituents of cell walls. For example, tetanus and diphtheria vaccines contain inactivated toxins (toxoids), influenza vaccine contains a surface protein called haemagglutinin, and pneumococcal vaccine contains the polysaccharide from the capsule. From birth and in early infancy and childhood, humans are exposed to countless numbers of foreign antigens and infectious agents in the everyday environment. Compared with exposure in the natural environment, vaccines provide specific stimulation to a small number of antigens. Responding to these specific antigens uses only a tiny proportion of the capacity of an infant’s immune system (Offit et al. If an infant’s immune system could be exhausted by multiple vaccines, one would expect vaccinated children to be at a higher risk of serious infections. Studies to investigate whether vaccines increase susceptibility to serious infections have shown no evidence of such an effect, with infection rates generally being lower in vaccinated children (Hviid et al. Inactivated vaccines A first injection of an inactivated vaccine or toxoid in an individual without prior exposure to the antigen produces a primary antibody response. Depending on the potency of the product and the time interval, further injections will lead to an accelerated response dominated by IgG – the secondary response. Following a primary course of vaccination, antibodies may persist for months or years. Even if the level of detectable antibody subsequently falls, the immune system has been primed and an individual may be protected. Further reinforcing doses of vaccine are used to boost immunity and to provide longer-term protection. Plain polysaccharide antigens do not stimulate the immune system as broadly as protein antigens such as tetanus, diphtheria or influenza. Therefore, protection from such vaccines is not long-lasting and response in infants and young children is poor. Some polysaccharide vaccines have been enhanced by conjugation – where the polysaccharide antigen is attached to a protein carrier. This enables the immune system to 3 Immunity and how vaccines work respond more broadly to the antigen to provide immunological memory, even in young children. Some inactivated vaccines contain adjuvants, substances that enhance the antibody response. Most combination vaccines contain adjuvants such as aluminium phosphate or aluminium hydroxide. To produce an immune response, the live organism must replicate (grow) in the vaccinated individual over a period of time (days or weeks). It usually does this without causing the disease itself (because the vaccine virus is weakened or ‘attenuated’) but, for some vaccines, a mild form of the disease may rarely occur. Vaccine failure No vaccine offers 100% protection and a small proportion of individuals get infected despite vaccination. Vaccines can fail in two main ways – known as primary or secondary vaccine failures. Primary failure occurs when an individual fails to make an initial immunological response to the vaccine. The risk of measles in such children is reduced by offering an additional dose of vaccine, usually before school entry. Secondary failure occurs when an individual responds initially but then protection wanes over time. Individuals who acquire infection despite vaccination may have a modified, milder form of disease and are less likely to suffer serious complications than those who have never been vaccinated. An example of secondary vaccine failure is pertussis vaccine, when protection against whooping cough after three doses is initially high but declines as a child gets older. Population immunity the primary aim of vaccination is to protect the individual who receives the vaccine. Vaccinated individuals are also less likely to be a source of infection to others. This reduces the risk of unvaccinated individuals being exposed to 4 Immunity and how vaccines work infection. This means that individuals who cannot be vaccinated will still benefit from the routine vaccination programme. For example, babies below the age of two months, who are too young to be immunised, are at greatest risk of dying if they catch whooping cough. Such babies are protected from whooping cough because older siblings and other children have been routinely immunised as part of the childhood programme. When vaccine coverage is high enough to induce high levels of population immunity, infections may even be eliminated from the country, e. But if high vaccination coverage were not maintained, it would be possible for the disease to return. Vaccination against smallpox enabled the infection to be declared eradicated from the world in 1980. Immunoglobulins Passive immunity can be provided by the injection of human immunoglobulin which contains antibodies to the target infection and temporarily increases an individual’s antibody level to that specific infection. Specific immunoglobulins are available for tetanus, hepatitis B, rabies and varicella zoster.
It is applied as a cream to weight of epinephrine (g) per volume of solution the skin and produces surface analgesia in approx- (mL) discount flavoxate spasms right abdomen. Local anaesthetics containing vasoconstrictors must never be used around extremities purchase flavoxate canada muscle relaxant pills. The maximum safe dose in an adult is 250mg cheap flavoxate 200 mg line muscle relaxant medications, that is, 20mL of 1:80000 or 50mL of 1:200000. This Management of toxicity should be reduced by 50% in patients with is- chaemic heart disease. If a patient complains of any of the above symp- toms or exhibits signs, stop giving the local anaes- thetic immediately! The next steps consist of: Calculation of doses • Airway Maintain using basic techniques. For any drug it is essential that the correct dose is Tracheal intubation will be needed if the protective given and the maximum safe dose never exceeded. This can be confusing with local anaesthetic drugs • Breathing Give oxygen (100%) with support of as the volume containing the required dose will ventilation if inadequate. If no major pulse is palpable, start external Concentration % ? Volume mL 10 dose mg cardiac compression. If inotropes and vasopressors are required, invasive monitoring will be needed and this should be performed on the intensive care Local anaesthetic toxicity unit. This is usually the result of one of the following: • Convulsions These must be treated early. If the convulsions do not respond or also occur during intravenous regional anaesthesia they recur, then seek assistance. In this way the pa- • Administration of an overdose Failure or error in tient will recover without any permanent sequelae. These are dependent on the plasma problem of anaesthesia in patients regarded as not concentration and initially may represent either a well enough for general anaesthesia. The decision mild toxicity or, more signi?cantly, the early stages to use any of these techniques should be based on of a more severe reaction. The following are some of the considerations of the tongue, visual disturbances, lightheaded- taken into account. This the latter two techniques are more correctly called may be important in underdeveloped areas. The fol- analgesia and muscle relaxation provided by the lowing is a brief introduction to some of the more regional technique. Initial objections and fears are best alleviated, and usually overcome, by explanation of the containing epinephrine can be used if a large dose advantages and reassurance. In?ltration analgesia is not instantaneous and lack of patience Whenever a local or regional anaesthetic tech- is the commonest reason for failure. The technique nique is used, facilities for resuscitation must used is as follows: always be immediately available in order that aller- • Calculate the maximum volume of drug that can gic reactions and toxicity can be dealt with be used. At a minimum this will include the • Clean the skin surrounding the wound with an following: appropriate solution and allow to dry. Contraindications are relatively few but include patients with impaired peripheral circulation or sickle-cell disease. Brachial plexus block the nerves of the brachial plexus can be anaes- thetized by injecting the local anaesthetic drug either above the level of the clavicle (supraclavicu- lar approach) or where they enter the arm through the axilla along with the axillary artery and vein (axillary approach). As the block may last several hours, it • Aspirate to ensure that the tip of the needle does is important to warn both the surgeon and patient not lie in a blood vessel. This When suturing, the needle is inserted into an area space extends from the craniocervical junction at of intact skin at one end of the wound and C1 to the sacrococcygeal membrane, and anaes- advanced parallel to the wound, and local anaes- thesia can theoretically be safely instituted at any thetic is injected as described. In practice, an epidural is sited local anaesthetic can be injected directly into the adjacent to the nerve roots that supply the surgical exposed wound edge. This technique can be also site; that is, the lumbar region is used for pelvic and used at the end of surgery to help reduce wound lower limb surgery and the thoracic region for ab- pain postoperatively. The 15mins and the duration is limited by discomfort (Tuohy) needle is advanced until its tip is embed- caused by the tourniquet. Sensation returns soon ded within the ligamentum ?avum (yellow liga- after release of the tourniquet. Correct resistance to attempted injection of either air or functioning of the tourniquet is essential other- saline from a syringe attached to the needle. As the wise there is the risk of the patient being given the needle is advanced further, the ligament is pierced, 65 Chapter 2 Anaesthesia Dura Dura — not punctured Epidural space Ligamentum flavum Spinous process Tuohy needle (a) Dura — pierced by needle Ligamentum flavum Spinous process Figure 2. The catheter is surgical anaesthesia with muscle relaxation, but marked at 5cm intervals to 20cm and at 1cm only 0. If the depth of the anaesthetic will spread from the level of injection epidural space is noted, this allows the length of both up and down the epidural space. For a given volume, spread is greater in the thoracic re- gion than in the lumbar region. The spread of anaesthesia is described with refer- ence to the limits of the dermatomes affected; for example: the inguinal ligament, T12; the umbili- cus, T10; and the nipples, T4. Technical note: the in?uence of using an atraumatic needle on the incidence of thetics and opioids for postoperative analgesia, see post-myelography headache. Spinal anaesthesia • Positioning of the patient either during or after Spinal (intrathecal) anaesthesia results from the in- the injection. The spinal needle can only be in- will extend to the thoracic nerves around T5–6, the serted below the second lumbar and above the ?rst point of maximum backwards curve (kyphosis) of sacral vertebrae; the upper limit is determined by the thoracic spine. Further extension can be ob- the termination of the spinal cord, and the lower tained with a head-down tilt. This extends the duration of analgesia for postdural puncture headache (see below). Posture is then used to Maintenance of verbal contact with the patient is control spread. If this is not possible then it may be necessary to convert to general anaesthesia. Early signs of inadequate cardiac output are effective, particularly if there is a bradycardia. The ?rst indication of extensive intravenously), but this must not be at the expense spread of anaesthesia may be a complaint of dif of the above. Clearly, these valuable signs and symptoms will be lost if the patient is heavily sedated. The incidence is greatest with large holes, that is, when a hole is These are usually mild and rarely cause any lasting made accidentally with a Tuohy needle, and least morbidity (Table 2. Their management Patients usually complain of a headache that is is covered below. Complications seen in patients frontal or occipital, postural, worse when standing receiving epidural analgesia postoperatively are and exacerbated by straining. Persistent headaches can be relieved (>90%) by injecting 20–30mL of the Hypotension and bradycardia patient’s own venous blood into the epidural space (epidural blood patch) under strict aseptic Anaesthesia of the lumbar and thoracic nerves conditions.
Prevention Preventive strategies against schistosomiasis include the following: Avoid contact with contaminated water purchase flavoxate from india muscle spasms zoloft. Improve environmental hygiene cheap flavoxate 200 mg without a prescription spasms near ovary, for example by advocating for the use of toilets by communities purchase generic flavoxate on-line muscle relaxant norflex. In either case, there may be frank red blood or altered blood that would appear as coffee grounds or there may be black stool. Among the common causes of features of upper gastrointestinal bleeding are: For the newborn • Swallowed maternal blood: In this situation the baby looks well. Infants and children • Swallowed blood following epistaxis (history of epistaxis). It should be noted that some normal babies regurgitate milk regularly and are clinically normal with normal growth. Vomiting may also be due to upper gastrointestinal tract obstruction, and may be the primary presentation for this condition. Initiate rehydration according to degree of dehydration, using normal saline in the acute phase. Arrange to transfer to surgical unit urgently all children suspected to have gastrointestinal obstruction and gastro-oesophageal reflux disease syndrome. Reflux precautions: Head up 30 degrees, side position to sleep Upright after feeding for 30 minutes Minimal handling after feeding Small frequent feeds Thicken feeds Medications: Acid suppression: Omeprazole 0. Clinical Features of Duodenal Ulcer Duodenal ulcer has the following features: Presents with epigastric pain that is typically nocturnal and also when the patient is hungry. May present for the first time with complications as described later in this section. There is a wide individual variation in presenting symptoms and in the foods that give pain or discomfort when eaten. Give magnesium-based antacids or combined magnesium-aluminium compounds, liquid preferred. Continue to assess for any further loss of blood as evidenced by: Persistent tachycardia, postural hypotension, continuing haematemesis. Encopresis is intermittent leakage of soft/watery stool in a child with chronic constipation. Constipation may be caused by obstructive lesions (these include congenital or acquired defects), neurological or endocrine abnormalities (hypothyroidism), or they may be functional. Note: Exclusively breastfed infants may take several days without passing a stool. Such treatment may make it difficult to diagnose this condition and may lead to some complications. However, the inclusion of bananas or pawpaw in the diet may be beneficial, especially in increasing fibre intake. Treatment of functional constipation is in three stages: Disimpaction (2–5 days): Mineral oils taken orally is the preferred treatment but daily enemas using magnesium salts can also be used. Sustained evacuation (about 3 months): this aims to restore normal bowel function. Child is encouraged to use toilet at regular intervals with positive rewards; diet is gradually modified to a low diary, high fibre one once disimpaction is achieved. Refer All children with suspected nonfunctional lesions Any child that fails to respond to above treatment Children in need of psychological counselling 33. Enlargement of the spleen, on the other hand, is reported to have occurred if the spleen is “just palpable”. Investigations Full blood count and blood film Liver biopsy when indicated Bone marrow if needed Specific tests will depend on the suspected cause listed in the table 254 Levels 4–6 – Hospitals Table 33. It is also referred to as hyperbiliribinaemia, usually with serum bilirubin at that time of >2mg% (34. Any patient with jaundice should be carefully evaluated to determine the cause of the jaundice so as to institute appropriate management. Hyperbilirubinaemia is categorized according to the location of the abnormality in the metabolism and excretion of bilirubin: pre-hepatic, hepatic, or post-hepatic: • Pre-hepatic: This is due to excess intravascular release of bilirubin, often by haemolysis) • Hepatic: This is due to hepatocyte dysfunction with faulty uptake, metabolism, or excretion of bilirubin. The common causes of hyperbilirubinaemia include viral hepatitis, haemolytic anaemia. The history should include exposure to hepatotoxic drugs, known history of haematological disorder, history suggestive of viral hepatitis (anorexia, nausea, and aversion to fatty foods), history suggestive of obstructive jaundice (of dark urine, pale stool and pruritus) Physical examination should look for features suggestive of cirrhosis (spider naevi, gynaecomastia, loss of axillary hair, parotid gland enlargement and ascites) or features suggestive of parenchymal liver disease or haemolytic jaundice (splenomegaly). In hepatic encephalopathy in children the early signs may be mild and easy to miss. Investigations Full haemoglobin – Polymorphonuclear leucocytosis is found in infections including leptospirosis. Sickle cells may be seen in the peripheral blood smear Reticulocyte count – Increased reticulocyte count indicates a haemolytic anaemia. Blood slide for malaria parasites – Jaundice in a patient with malaria is a medical emergency. Urine – Bilirubin: • Absence of bilirubin in a patient suggests haemolytic anaemia. Ultrasound: Useful in obstructive jaundice, gall stones, differentiating between abscess and tumour. Alpha-foetoproteins: Substantial elevations of alpha-foetoproteins are found in malignancy. Protein content >3g% is found in tuberculosis, peritoneal tumours, peritoneal 256 Levels 4–6 – Hospitals infection or hepatic venous obstruction. Blood stained ascites usually indicates a malignant disease – cytology is mandatory. Liver biopsy is important in diagnosis of chronic hepatitis, cirrhosis, and hepatocellular malignancy. Management Patients with history and physical findings suggestive of viral hepatitis can be managed as outpatients requiring advice on bed rest and should be given multivitamins. Consider hepatic encephalopathy in any patient who has jaundice and mental complaint. Clinical Features These include the following features: Jaundice and pruritus, which can be severe, with steady increase in jaundice Distended gall bladder Anorexia Troublesome diarrhoea with pale, foul smelling stool. Those acting outside the wall or extramural include enlarged lymph nodes of any cause, and neoplasms. Other causes include iatrogenic trauma to the ducts during surgery (especially cholecystectomy). The average normal haemoglobin levels for the various ages in childhood are shown in Table 32. The common causes of anaemia in Kenya are the following: Haemolysis of red blood cells caused by infections like malaria or congenital abnormalities like haemoglobinopathies exemplified by sickle cell disease.
Syndromes
Allele frequencies tend to change from one generation to the next simply as a result of sampling error buy generic flavoxate on-line spasms medication. We can specify a probability distribution for the allele frequency in the next generation order flavoxate 200 mg visa infantile spasms 2012, but we cannot predict the actual frequency with certainty order flavoxate cheap online spasms compilation. The allele frequency is as likely to increase from one generation to the next as it is to decrease. If the process is allowed to continue long enough without input of new genetic material through migration or mutation, the population will eventually become fixed for only 13 one of the alleles originally present. The time to fixation on a single allele is directly proportional to population size, and the amount of uncertainty associated with allele frequencies from one generation to the next is inversely related to population size. Effective population size I didn’t make a big point of it, but in our discussion of genetic drift so far we’ve assumed everything about populations that we assumed to derive the Hardy-Weinberg principle, and we’ve assumed that: • We can model drift in a finite population as a result of sampling among haploid gametes rather than as a result of sampling among diploid genotypes. Since we’re dealing with a finite population, this effectively means that the two gametes incorporated into an individual could have come from the same parent, i. One way would be to develop all the probability models that incorporate that complexity and try to solve them. Another, and by far the most common approach, is to come up with a conversion formula that makes our actual population seem like the “ideal” population that we’ve been studying. The effective size of a population is the size of an ideal population that has the same properties with respect to genetic drift as our actual population does. Variance effective size 18 You may remember that the variance in allele frequency in an ideal population is pt(1 − pt) V ar(pt+1) =. We do this by calculating the variance in allele frequency for our actual population, figuring out what size of ideal population would produce the same variance, and pretending that our actual population is the same as an ideal population of 19 d the same size. To put that into an equation, let V ar(p) be the variance we calculate for our actual population. Inbreeding effective size You may also remember that we can think of genetic drift as analogous to inbreeding. We do this by calculating how the inbreeding coefficient changes from one generation to the next in our actual population, figuring out what size an ideal population would have to be to show the same change between generations, and pretending that our actual population is the same size at the ideal one. So suppose fˆ and fˆ are the actual inbreeding coefficients we’d have t t+1 in our population at generation t and t + 1, respectively. Comments on effective population sizes (v) (f) Those are nice tricks, but there are some limitations. The biggest is that Ne 6= Ne if the 20 population size is changing from one generation to the next. So you have to decide which of these two measures is more appropriate for the question you’re studying. When the population size is changing, it’s not clear that any of the available adjustments to produce an effective population size are entirely satisfactory. It tells you something about how the probability of identity by descent within a single population will change over time. It tells you something about how much allele frequencies in isolated populations will diverge from one another. In the case of differences in the number of offspring left by individuals, I’ll just give you the formula and we’ll discuss some of the implications. Separate sexes We’ll start by assuming that fˆ = 0 to make the calculations simple. Thus, the probability that the first gamete selected at random is female is just 1/2, and the probability that the first gamete selected is male is just 1/2. Similarly the probability that one particular male gamete was chosen is 1/2Nm, where Nm is the number of males in the population. Suppose the numbers of females and males in a population are equal, Nf = Nm = N/2. The effective population size is equal to the actual population size if the sex ratio is 50:50. If it departs from 50:50, the effective population size will be smaller than the actual population size. Consider the extreme case where there’s only one reproductive male in the population. Since the population size is changing we need to specify the population size at each time step. It’s another well-known fact that the harmonic mean of a series 23Well known to some of us at least. This means that genetic drift may play a much more imporant role than we might have imagined, since the effective size of a population will be more influenced by times when it is small than by times when it is large. Consider, for example, a population in which N1 through N9 are 1000, and N10 is 10. So the population will behave with respect to the inbreeding associated with drift like a population a tenth of its arithmetic average size. Re- member I told you that the number of gametes any individual has represented in the next generation is a binomial random variable in an ideal population? Well, if the population size 27 isn’t changing, that means that Vk = 2(1 − 1/N) in an ideal population. It can also be shown (with more algebra) that (f) • Ne < N if Vk > 2(1 − 1/N) and (f) • Ne > N if Vk < 2(1 − 1/N). Conservation biologists try to take advantage of it to decrease the loss of genetic variation in small populations, especially those that are captive bred. If you can reduce the variance in reproductive success, you can substantially increase the effective size of the population. We’ve also completely ignored the ultimate source of all genetic 1 variation — mutation. We’re now going to study what happens when we consider multiple populations simultaneously and when we allow mutation to happen. Drift and mutation Remember that in the absence of mutation 1 1 ft+1 = + 1 − ft, (13. This model is referred to as the infinite alleles model, because it implicitly assumes that there is potentially an infinite number of alleles. We have to multiply the expression on the right by the probability that neither allele mutated: 1 1 2 ft+1 = + 1 − ft (1 − µ), (13. In writing down this expression, the reason this is referred to as an infinite alleles model becomes apparent: we are assuming that every time a mutation occurs it produces a new allele. Well, if you think about it, mutation is always introducing new alleles that, by definition, are different from any of the alleles currently in the population. It stands to reason, therefore, that we’ll never be in a situation where all of the alleles in a population are identical by descent as they would be in the absence of mutation. In other words we expect there to be an equilibrium between loss of diversity through genetic drift 3 and the introduction of diversity through mutation. From the definition of an equilibrium, 1 1 2 fˆ = + 1 − fˆ (1 − µ) 2N 2N 1 2 1 2 fˆ 1 − 1 − (1 − µ) = (1 − µ) 2N 2N 1 2 (1 − µ) ˆ 2N f = 1 2 1 − 1 − (1 − µ) 2N 1 − 2µ ≈ 1 2N 1 − 1 − (1 − 2µ) 2N 1 − 2µ = 1 2µ 2N 1 − 1 + + 2µ − 2N 2N 1 − 2µ = 1 + 4Nµ − 2µ 1 ≈ 4Nµ + 1 Since f is the probability that two alleles chosen at random are identical by descent within our population, 1 − f is the probability that two alleles chosen at random are not 2Notice that we’re also playing a little fast and loose with definitions here, since I’ve just described this in terms of identity by type when what the equation is written in terms of identity by descent.
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