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Rudolf Virchow purchase levitra soft amex erectile dysfunction icd 0, the founder of cell pathology levitra soft 20 mg erectile dysfunction doctors tucson az, compared the human body to the state buy 20 mg levitra soft free shipping erectile dysfunction tulsa, and the cells to the citizens order levitra soft in india erectile dysfunction bangalore doctor. Weindling showed how these ideas had 31 formed the foundation of Nazi health policy. Lord Rosebery, the future leader of the Liberal party, addressed an audience at Glasgow University in 1900 and stated that: An Empire such as ours requires as its first condition an Imperial Race - a race vigorous and industrious and intrepid. The survival of the fittest is an absolute truth in 32 the conditions of the modern world. Food reformers, such as the national tennis champion, Eus- tace Miles, in his 1902 book, Avenues to Health, advocated the establishment of a national diet, which would increase the vitality and the moral strength of the nation. Health was a duty: to ourselves, to our own nation, to all nations, and to 33 posterity. This combination of social Darwinism, moralism, and lifestyl- ism is strikingly similar to the modern ideology of healthism. Who now remembers what Henri de Mondeville wrote in 1320 in his Chirurgie: Anyone who believes that anything can be suited to every- one is a great fool, because medicine is practised not on 34 mankind in general, but on every individual in particular. Health was normality, disease was either the result of an unhealthy lifestyle or a sign of heredi- tary degeneration. The glorification of health (which was equated with beauty) and the inculpation of the sick received whole-hearted support from the medical profession. Only in 152 Coercive medicine the last decade has it become possible in Germany to examine objectively the ideology of public health in Nazi Germany, and many excellent German language analyses are now available. Professional secrecy was no longer a binding precept, as the public good had to take precedence over individual interest. The misuse of tobacco and alcohol were the greatest threats to the national health, for which the liberalism of the pre-Nazi era was blamed. The criteria of a useful life were in men, the ability to fight for the fatherland, and in women, to bear healthy, racially pure 35 children. Tobacco manufacturers were prohibited from advertising their products by appealing to women, sports- 36 men, or car-drivers. Even the leisure time of workers needed state supervision, in a system called Freizeitgestaltung (organisation of free-time). Communist medicine was first outlined in Voyage en Icarie by Etienne Cabet (1788-1856), a French revolutionary and a follower of Babeuf. In Icaria, the ideal communist state, the doc- tor did not have to depend on private practice as he was a salaried member of the community and medical service was free for all. Intemperate drinking and eating, lack of exercise, sexual overindulgence or tobacco smoking (about which Cabet had particularly strong feelings) were not tolerated. Only those individuals who had desirable mental and physical qualities were allowed to have children. None of this required imposition from above, as it was supported by a national democratic consensus. The results of decades of health promotion in communist countries should be carefully studied and evaluated by those who intend to introduce similar principles in Western democracies. What benefits, for example, have been observed in state-organised, compul- sory cervical cancer screening programmes in communist countries? When a delegation of prominent British physicians visited Russia in 1960, they were impressed by the Soviet emphasis on health promotion. While many middle-aged men and women appear drab and weary, the children and young people seem to be healthy, happy, and friendly. Von Mises makes the point that the difference between communism and fascism on the one hand, and socialism on the other is only 39 in the means by which to achieve identical ends. This per- manent tutelage, which von Mises called etatism, and British commentators call the nanny state, exists, as yet, in Western democracies only in a diluted version because of various con- stitutional, philosophical, moral and political obstacles. As Talmon showed, the Left starts from the premise that man is perfectible, as Rousseau believed, and by changing the unhealthy environment, created by an unfettered capitalism, man can be made healthy and happy, even though at times some degree of coercion might become necessary. For example, the poor are known to suffer more from diseases and have shorter life-expectancy, but should this be blamed on their lifestyle or on the political conditions which are the causes of poverty? By linking poverty with disease (which is not unreasonable on its own), Marxists promise that in a classless society the health of the poor will improve. Furthermore, the Left, in their various health manifestos, propose increased powers to prescribe healthy activities and proscribe unhealthy activities. To maintain the nation in a high state of readiness to defend the supremacy of the race, people should be responsible for their own health. Typical political statements are contained in Department of Health documents which see health as a matter over which the individual has control and responsibility. It makes little difference to the citizen whether statements such as the list of national targets for physical activity in England, issued by the Faculty of Public Health Medicine in February 1993, emanate from the Left or the Right, as in either case the citizen is threatened by the tyranny of the majority, if he chooses not to fulfil his quota of exercise. Any prescriptive system to make man free, or healthy, ends by enslaving him, or by taking health away from him. Those who conform, whether out of greed, cowardice, stupidity or genuine enthusiasm. Fascism and communism are histori- cal forms of totalitarianism which are unlikely to re-emerge in the same form in Western democracies, and even less so under the same name. The brave new world of the year 2000 is being heralded in the name of medical science, genetics, and the promise of longevity. The criminalisation of motherhood was dis- cussed by Ernest Drucker, professor of epidemiology and social medicine at Montefiore Medical Center in the Bronx, where about a quarter of all women who give birth use drugs, 46 such as cocaine. About half of the newborn babies who test positive for drugs are removed from their mothers and placed in foster care. Drucker illustrated this practice in a case of a poor Puerto-Rican woman, whose baby was taken away from her after birth. She had a complication of pregnancy known as placenta praevia and the baby died shortly after birth. Annas asked: Does it make any sense to decree that the pregnant woman must, in effect, live for her foetus? That she commits a crime if she does not eat only healthy foods; smokes cigarettes or drinks alcohol; takes drugs (legal or illegal); has intercourse with her husband? Favouring the foetus radically devalues the pregnant woman, and treats 158 Coercive medicine her like an inert incubator, or as a culture medium for the foetus. Women have always been unequal citizens, at least in medical eyes, but this has been obscured by the rhetoric of equality. Women have been barred from employment that was con- sidered harmful to a foetus, even if they were not pregnant. In 1978, American Cyanamid banned all women of childbear- ing age (defined as 16 to 50) from their plant in West Virginia, unless they could prove that they had been sterilised. Free sterilisation was offered and five women accepted it rather 48 than being dismissed. A Nevada woman who drank some beer the day 49 before she went into labour lost custody of her child. The New England Journal of Medicine reported 21 such cases in women who were, as a rule, single, poor, and coloured; Acceptance of forced caesarean sections, hospital deten- tions, and intra-uterine transfusions may trigger demands for court-ordered pre-natal screening, foetal surgery, and restrictions on the diet, work, athletic activity and sexual 50 activity of pregnant women. The woman did not consent, so she was brought to court, where her doctor claimed that there was a 99 per cent probability that the child would die and a 50 per cent probability that the mother would die, if a caesarian section was not performed. She won an appeal to the Georgia Supreme Court and, shortly after- wards, delivered a healthy baby without surgical inter- 52 vention. While some women may be forced to keep their pregnancy against their will others may be prevented from becoming pregnant. It usually takes some 15-20 years before American fashions in public health are adopted in Britain. Yet a High Court in London, in October 1992, ordered an emergency caesarean section on a 30-year-old woman, who refused the operation on religious grounds. In 1992, in Erlangen, Germany, an 18-year-old woman was killed in a car accident and since she was carrying a four-month-old 160 Coercive medicine foetus it was decided to keep the brain-dead woman on a life-support machine until the baby could be delivered. Police powers may even extend to forcing women to undergo a gynaecological examination if there is a suspicion that they have had an illegal abortion abroad. According to a study carried out in 1991 by the Max Planck Institute for Foreign and International Law in Freiburg, there were about ten such cases a year, especially in women returning to Ger- 58 many from the Netherlands. As early as 1963, Erwin Goffman noted that: Only one completely unblushing male in America is a young, married, white, urban, northern, heterosexual Protestant father of college education, fully employed, of good complexion, weight and height and a recent record 60 of sports. Medical screening of healthy humans is the latest addition to collecting information on private citizens. It is the apparent benevolence of the purposes of health screening - to prevent disease and to prolong life - which makes it particularly dangerous, as its more sinister aspects go unnoticed. Epidemiologists, physicians, and other policy makers often treat an estimate of the likelihood of something happening 62 to an individual as an important fact about him. This new statistical or actuarial concept of risk only became part of health promotion rhetoric in the 1970s. This develop- 162 Coercive medicine ment is in line with the neopuritanical tendency towards nor- malisation. Yet, clearly, it is not homosexuality which causes the disease, and even if all homosexuals were exterminated, it would not eradicate the disease. In general, the study of risk factors and their detection in individuals does not bring us nearer to an understanding of causal mechanisms. More often than not, risk factors obscure rather than illuminate the path towards a proper understand- ing of cause. Hagen Kuhn pointed out that prevention based on risk-factor epidemiology is governed by the kind of logic by which room temperature may be lowered by placing the 65 room thermometer into a bucket of ice. The information which accrues from risk-factor screening is hardly ever of any benefit to the person screened, but is of advantage to screeners.

Compared with category D generic 20 mg levitra soft with amex impotence hypertension, with only one to three cases reported purchase on line levitra soft erectile dysfunction after vasectomy, category C (<12 and >4 case reports) drugs were more likely to have rechallenge reports levitra soft 20mg visa losartan causes erectile dysfunction, with 26% vs levitra soft 20 mg overnight delivery erectile dysfunction doctors fort lauderdale. A positive rechallenge is usually defined with biochemical criteria, showing recurrence of liver test abnormalities upon readministration of the drug, due to either intentional or inadvertent re-exposure [4,5]. This is generally considered to be the gold standard of the diagnosis of drug-induced liver injury. A documented positive rechallenge provides more evidence of the hepatotoxicity of a Int. Given the frequency of case reports with drugs in categories A and B, there seems little doubt that drugs in these categories can lead to hepatotoxicity and little need to do a strict causality assessment of reports with these drugs. However, in category C, consisting of 4–11 case reports, the hepatotoxicity of some drugs can be put into question. Thus, it can be concluded that these drugs do not have a well-documented hepatotoxicity, although liver injury with their use cannot be excluded. The poorly documented exclusion of competing causes, as well as the use of other concomitant drugs, made a causality assessment difficult. It is very important that observations of hepatotoxicity of new drugs should lead to well-documented case reports with detailed clinical and biochemical information. Table 3 illustrates the five most common drugs associated with liver injury in at least three prospective studies. In India, anti-tuberculous drugs (58%), anti-epileptics (11%), olanzapine (5%), and dapsone (5%) were the most common causes [16]. The 10 most frequently implicated drugs were: amoxicillin-clavulanate, flucloxacillin, erythromycin, diclofenac, sulfamethoxazole/Trimethoprim, isoniazid, disulfiram, Ibuprofen and flutamide [12–14,21]. Drugs with an intermediate risk were amoxicillin-clavulanic acid and cimetidine, with a risk of one per 10 per 100,000 users [24]. The limitations of this study were the retrospective design with a lack of complete data regarding diagnostic testing and a lack of data on over-the-counter drugs and herbal agents [24]. Amoxicillin-clavulanate-induced liver injury was found in one of 2350 outpatient users, which was higher among those who were hospitalized already, one of 729. This might be due to a detection bias, with more routine testing of the liver in the hospital, but it cannot be excluded that sicker patients are more susceptible to liver injury from this drug. The incidence rates were higher than previously reported, with the highest being one of 133 users for azathioprine and one of 148 for infliximab. Acknowledgments: No specific grants were obtained for research work presented in this paper and no funds for publishing in open access. Discrepancies in liver disease labeling in the package inserts of commonly prescribed medications. Categorization of drugs implicated in causing liver injury: Critical assessment based upon published case reports. Evolution of the Food and Drug Administration approach to liver safety assessment for new drugs: Current status and challenges. Drug-induced liver injury: An analysis of 461 incidences submitted to the Spanish registry over a 10-year period. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Incidence, presentation and outcomes in patients with drug-induced liver injury in the general population of Iceland. Single-center experience with drug-induced liver injury from India: Causes, outcome, prognosis, and predictors of mortality. The increased risk of hospitalizations for acute liver injury in a population with exposure to multiple drugs. A review of epidemiologic research on drug-induced acute liver injury using the general practice research data base in the United Kingdom. Acute and clinically relevant drug-induced liver injury: A population based case-control study. Sigurdsson and Gudmundur Thorgeirsson 1Solvangur Health Center of Hafnarfjo¨ rdur, 2Department of Family Medicine, University of Iceland, 3Department of Medicine, National University Hospital of Iceland. The article overviews the risk factors for cardiovascular disease and the strategies for primary prevention. An almost Strategies of primary prevention world-wide epidemic of obesity and diabetes is pre- For people at extraordinarily high risk, an individua- dicted for the future, not the least in the densely lised, patient-based approach is both a rational and populated countries of Asia, with consequences of an effective strategy. In the Nurse’s Health Study, women who ate a individuals can be identified and targeted for effective healthy diet, did not smoke, consumed a moderate intervention. In the Framingham study, hypertension amount of alcohol, exercised regularly and maintained was found to occur in isolation only about 20% of the time, but frequently coexisted with risk factors such as Table I. Although each risk factor is a public health problem in itself, they interact Modifiable Non-modifiable Á/ synergistically damaging the vasculature Á/ and have Smoking Age a tendency to cluster. Firstly, the risk relations are contin- independently or via the major risk factors, i. Behavioural change vention refers to both preventing the development of will be best accomplished by influencing the commu- disease as well as its risk factors, and primary nity (13). Because of the large number of people near the middle of the distribution, Smoking. Although this is common knowl- North Karelia Project in Finland (14), the Stanford edge, the important role of physicians and other health Three Community Study (15) and ‘‘Live for Life’’ care providers in helping people to stop smoking is less health promotion programme in Sweden (16). The simple The high-risk and population-based strategies are advice from a physician to stop smoking has been far from being mutually exclusive. On the contrary, shown to double the spontaneous rates of quitting in a they are mutually supportive. As many opportunities interventions are more likely to be successful in an as possible in the varied encounters between patients environment where healthy lifestyle habits are widely and the health care system should be used to ask practised. And those who practice high-risk interven- about smoking habits and to offer assistance to those tions are important champions and educators of the who are ready to fight the habit. It should, however, be kept in mind that it is an uphill struggle to give up smoking and there are strong commercial and social forces that promote smoking, especially among the young. In some countries a positive change has been noted with the prevalence of smoking decreasing (5,16). Elevated blood pressure is a well- established preventable risk factor for the development of all manifestations of atherosclerosis, coronary heart disease, stroke, peripheral artery disease and heart Fig. The aim of primary blood pressure is an equally strong risk factor as prevention is to shift the curve toward the left, i. Both mendations emphasise the importance of repetitive sets of guidelines emphasise that recommendations measurements of blood pressure, sometimes over a must be based not only on lipid measurements but also period of several months, for the accurate assessment on assessment of the absolute coronary risk projected of blood pressure Á/ which is needed for the decision by a total risk profile. L may require cholesterol-lowering drug treatment in Fundamental to that decision is the assessment of a patient with high overall coronary risk, whereas a the patient’s overall cardiovascular risk profile, be- serum cholesterol level of 7Á/8 mmol/L may be left cause the detrimental impact of blood pressure is untreated, except for lifestyle advice, in an individual determined by the presence or absence of other risk with low absolute risk (7). Lifestyle calls for lifestyle recommendations for a period of a interventions are important and in some cases can be few months, and if risk reduction is insufficient drug sufficient for adequate control. The safety and tions should be given to all patients considered to have efficacy of statin therapy in the primary prevention hypertension. Weight control, reduction in the use of setting is based on robust trial evidence (31). Drug below 3 mmol/L is ideal for the whole population and treatment is recommended if the systolic blood a worthwhile public health goal is to achieve these pressure is ]/160 and/or diastolic pressure ]/100 levels with appropriate diet and regular physical mmHg, despite lifestyle interventions. Risk factor saturated fats and cholesterol in a given population management in this patient group is extremely im- and the usual levels of serum cholesterol in that portant. Consequently, in viously discussed, a population strategy should be newly published recommendations from the American augmented by the individualised clinical approach of Diabetes Association, the target goal for hypertensive physicians identifying those who need urgent and treatment among diabetes patients is set at B/130/80 aggressive risk factor modification, including drug mmHg, and it is recommended that this should be treatment and family screening. Most recently, the beginning in childhood, should be one of the most Steno-2 study from Denmark (39) has demonstrated important health priorities for the years to come. The intensive treatment relative risk as smoking, hypercholesterolaemia or involved stepwise introduction of lifestyle and phar- hypertension (47). Part of its complex effect may be included reduced intake of dietary fat, regular parti- mediated through enhanced fibrinolytic potential cipation in light or moderate exercise and abstinence and reduced platelet adhesiveness and thus reduced from smoking. Epidemiological stu- even in small doses aspirin can do more harm than dies have shown that the relationship between body good (54Á/56). Although the reduction in relative risk weight and mortality rate is J-shaped, the lowest may be similar in both primary and secondary mortality rate being among those with ‘‘normal’’ prevention, i. Because of this, one should be very careful to Heart Study (44) it was concluded that obesity in use drugs as a general mean of prevention unless the adulthood is associated with a decrease in life ex- benefits have been proven in well-conducted clinical pectancy of about 7 years in both men and women. Increased Several observational studies have suggested that intra-abdominal fat mass, i. Nevertheless, the The recent negative or neutral trial results with lifestyle recommendations given for one risk factor, oestrogen and vitamins (40), in both cases overturning for example hypertension or high serum cholesterol, conclusions from observational studies, demonstrate follow the same general principle as health recom- that in the field of prevention as in therapeutics we are mendations applicable for the public in general, i. The burden of elevated blood pressure, insulin resistance and glucose cardiovascular diseases mortality in Europe. Task Force of the European Society of Cardiology on Cardiovascular intolerance, a prothrombotic state and a proinflam- Mortality and Morbidity Statistics in Europe. Heart and stroke although pharmacological management of insulin statistical update. Dallas, Texas: American Heart Associa- resistance may hold a promise for the future. World another group and also patients met in ordinary Health Stat Q 1988;41:155Á/78. Changes in risk factors explain changes in mortality from Abdominal obesity (waist circumference) ischaemic heart disease in Finland. Singapore and coronary heart disease: a Women /88 cm population laboratory to explore ethnic variations in the Triglycerides /1. Report from the Oslo Study Group of a panel guide to comprehensive risk reduction for adult randomized trial in healthy men.

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Their implied argument was that if the methods were equivalent the slope of the regression line would be 1 trusted levitra soft 20 mg erectile dysfunction doctors in pa. However purchase levitra soft on line erectile dysfunction young male, this ignores the fact that both dependent and independent variables are measured with error buy generic levitra soft 20mg line erectile dysfunction divorce. In our previous notation the expected slope is 2 2 2 β = σT /(σA + σT ) and is therefore less than l generic levitra soft 20mg fast delivery erectile dysfunction vitamin b12. How much less than 1 depends on the amount of measurement error of the method chosen as independent. Similarly, the expected value of the intercept will be greater than zero (by an amount that is the product of the mean of the true values and the bias in the slope) so that the conclusion of Ross et al. We do not reject regression totally as a suitable method of analysis, and will discuss it further below. Asking the right question None of the previously discussed approaches tells us whether the methods can be considered equivalent. We think that this is because the authors have not thought about what question they are trying to answer. The questions to be asked in method comparison studies fall into two categories: (a) Properties of each method: How repeatable are the measurements? This may include both errors due to repeatability and errors due to patient/method interactions. Under properties of each method we could also include questions about variability between observers, between times, between places, between position of subject, etc. Most studies standardize these, but do not consider their effects, although when they are considered, confusion may result. Altman’s (1979) criticism of the design of the study by Serfontein and Jaroszewicz (1978) provoked the response that: “For the actual study it was felt that the fact assessments were made by two different observers (one doing only the Robinson technique and the other only the Dubowitz method) would result in greater objectivity” (Serfontein and Jaroszewicz, 1979). What we need is a design and analysis which provide estimates of both error and bias. We feel that a relatively simple pragmatic approach is preferable to more complex analyses, especially when the results must be explained to non-statisticians. It is difficult to produce a method that will be appropriate for all circumstances. What follows is a brief description of the basic strategy that we favour; clearly the various possible complexities which could arise might require a modified approach, involving additional or even alternative analyses. Properties of each method: repeatability The assessment of repeatability is an important aspect of studying alternative methods of measurement. Replicated measurements are, of course, essential for an assessment of repeatability, but to judge from the medical literature the collection of replicated data is rare. Repeatability is assessed for each measurement method separately from replicated measurements on a sample of subjects. We obtain a measure of repeatability from the within- subject standard deviation of the replicates. The British Standards Institution (1979) define a coefficient of repeatability as “the value below which the difference between two single test results. Provided that the differences can be assumed to follow a Normal distribution this coefficient is 2. For the purposes of the present analysis the standard deviation alone can be used as the measure of repeatability. It is important to ensure that the within-subject repeatability is not associated with the size of the measurements, in which case the results of subsequent analyses might be misleading. The best way to look for an association between these two quantities is to plot the standard deviation against the mean. If there are two replicates x1 and x2 then this reduces to a plot of | x1 – x2| against (x1 + x2)/2. From this plot it is easy to see if there is any tendency for the amount of variation to change with the magnitude of the measurements. The correlation coefficient could be tested against the null hypothesis of r = 0 for a formal test of independence. If the within-subject repeatability is found to be independent of the size of the measurements, then a one-way analysis of variance can be performed. The residual standard deviation is an overall measure of repeatability, pooled across subjects. If, however, an association is observed, the results of an analysis of variance could be misleading. Several approaches are possible, the most appealing of which is the transformation of the data to remove the relationship. If the relationship can be removed, a one-way analysis of variance can be carried out. Repeatability can be described by calculating a 95 per cent range for the difference between two replicates. In the case of log transformation the repeatability is a percentage of the magnitude of the measurement rather than an absolute value. It would be preferable to carry out the same transformation for measurement by each method, but this is not essential, and may be totally inappropriate. Alternatively, the repeatability can be defined as a function of the size of the measurement. Properties of each method: other considerations Many factors may affect a measurement, such as observer, time of day, position of subject, particular instrument used, laboratory, etc. The British Standards Institution (1979) distinguish between repeatability, described above, and reproducibility, “the value below which two single test results. There may be difficulties in carrying out studies of reproducibility in many areas of medical interest. For example, the gestational age of a newborn baby could not be determined at different times of year or in different places. When effects are fixed, for example when comparing an inexperienced observer and an experienced observer, the approach used to compare different methods, described below, should be used. Comparison of methods The main emphasis in method comparison studies clearly rests on a direct comparison of the results obtained by the alternative methods. The question to be answered is whether the methods are comparable to the extent that one might replace the other with sufficient accuracy for the intended purpose of measurement. Plots of this type are very common and often have a regression line drawn through the data. The appropriateness or regression will be considered in more detail later, but whatever the merits of this approach, the data will always cluster around a regression line by definition, whatever the agreement. For the purposes of comparing the methods the line of identity (A = B) is much more informative, and is essential to get a correct visual assessment of the relationship. An example of such a plot is given in Figure 1, where data comparing two methods of measuring systolic blood pressure are shown. Although this type of plot is very familiar and in frequent use, it is not the best way of looking at this type of data, mainly because much of the plot will often be empty space. Also, the greater the range of measurements the better the agreement will appear to be. It is preferable to plot the difference between the methods (A – B) against (A + B)/2, the average. From this type of plot it is much easier to assess the magnitude of disagreement (both error and bias), spot outliers, and see whether there is any trend, for example an increase in A – B for high values. This way of plotting the data is a very powerful way of displaying the results of a method comparison study. It is closely related to the usual plot of residuals after model fitting, and the patterns observed may be similarly varied. In the example shown (Figure 2) there was a significant relationship between the method difference and the size of measurement (r = 0. This test is equivalent to a test of equality of the total variances of measurements obtained by the two methods (Pitman, 1939; see Snedecor and Cochran, 1967, pp. Data from Figure 1 replotted to show the difference between the two methods against the average measurement. With independence the methods may be compared very simply by analysing the individual A – B differences. The mean of these differences will be the relative bias, and their standard deviation is the estimate of error. Also shown is a histogram of the individual between-method differences, and superimposed on the data are lines showing the mean difference and a 95 per cent range calculated from the standard deviation. A composite plot like this is much more informative than the usual plot (such as Figure 1). If there is an association between the differences and the size of the measurements, then as before, a transformation (of the raw data) may be successfully employed. In this case the 95 per cent limits will be asymmetric and the bias will not be constant. Additional insight into the appropriateness of a transformation may be gained from a plot of |A – B| against (A + B)/2, if the individual differences vary either side of zero. In the absence of a suitable transformation it may be reasonable to describe the differences between the methods by regressing A – B on (A + B)/2. For replicated data, we can carry out these procedures using the means of the replicates. We can estimate the standard deviation of the difference between individual measurements from the standard deviation of the difference between means by var(A – B) = n var( A – B ) where n is the number of replicates.

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Both ends may be exteriorised as small bowel characterised by a feeling of epigastric acolostomy and a mucous fistula or the rectal stump fullness after food associated with flushing order cheap levitra soft line erectile dysfunction pills over the counter, sweating can be closed off and left within the pelvis (Hartman’s 15–30 minutes after eating buy 20mg levitra soft overnight delivery erectile dysfunction causes cycling. Surgical re- 2 Ileostomy effective levitra soft 20 mg impotence and depression, which requires the creation of a cuff of vision may be indicated discount levitra soft 20 mg mastercard erectile dysfunction due to drug use. Prior to emergency surgery ag- gastrectomy after a latent period of 20 years possibly gressive resuscitation is required. Resection of tumours, due to bacterial overgrowth with the generation of when of curative intent, involves removal of an adequate carcinogenic nitrosamines from nitrates in food. Complications of intestinal surgery include wound Small bowel surgery infection (see page 16) and anastomotic failure, the Smallbowelresectionisnormallyfollowedbyimmediate treatment for which is surgical drainage and exteriori- end-to-end anastomosis as the small bowel has a plen- sation. Small to medium resections have little functional consequence as there is a relative func- Gastrointestinal infections tional reserve; however, massive resections may result in malabsorption. Definition r Nutritional consequences are severe when more than Bacterial food poisoning is common and can be caused 75% of the bowel is resected. Chapter 4: Gastrointestinal infections 149 Aetiology and pathophysiology severity of each symptom and a careful history of food r Bacillus cereus has an incubation period of 30 min- intake over the past few days may point in the direction utes to 6 hours. Ingested Investigations spores (which are resistant to boiling) may cause diar- Microscopy and culture of stool is used to identify cause. Recovery All forms of bacterial food poisoning are notifiable to occurs within a few hours. The onset oftheclinicaldiseaseoccurs2–6hoursafterconsump- Management tion of the toxins. Canned food, processed meats, milk In most cases the important factor is fluid rehydration and cheese are the main source. Antibioticsare istic feature is persistent vomiting, sometimes with a not used in simple food poisoning unless there is ev- mild fever. There is a large animal reservoir (cattle, sheep, Bacilliary dysentery rodents, poultry and wild birds). Patients present with fever, headache and malaise, followed by diarrhoea, Definition sometimes with blood and abdominal pain. Recovery Bacilliary dysentery is a diarrhoeal illness caused by occurs within 3–5 days. It has an in- There are four species of Shigella known to cause diar- cubation period of 12–24 hours and recovery occurs rhoeal illness: within 2–3 days. There are more than 2000 species on the basis of r Shigella flexneri and Shigella boydii (travellers) cause antigens, which can help in tracing an outbreak. Salmonella enteritidis (one common serotype is called r Shigella dysenteriae is the most serious. The main reservoir of infection is poul- try, though person to person infection may occur. Di- Pathophysiology arrhoea results from invasion by the bacteria result- Shigella is a human pathogen without an animal reser- ing in inflammation. Spread is by person-to-person contact, faecal–oral with fever, malaise, cramping abdominal pain, bloody route or contaminated food. Acutewaterydiarrhoeawithsystemicsymptomsoffever, malaise and abdominal pain develops into bloody di- Clinical features arrhoea. Other features include nausea, vomiting and As outlined above the cardinal features of food poison- headaches. Complications include colonic perforation, ing are diarrhoea, vomiting and abdominal pain. Severe cases may be treated mon in the developing world but also found in with trimethoprim or ciprofloxacin. Outbreaks may oc- the United Kingdom, especially in immunocom- cur and require notification and source isolation. It has been suggested from retrospective studies Aetiology/pathophysiology that treatment of E. The tox- Pseudomembranous colitis ins are coded for on plasmids and can therefore be Definition transferred between bacteria. The heat labile toxin Pseudomembranous colitis is a form of acute bowel in- resembles cholera toxin and acts in a similar way. Infections are associated with contaminated food, particularly hamburgers, Investigations only a small bacterial load is required to cause dis- r At sigmoidoscopy the mucosa is erythematous, ulcer- ease. Management The broad-spectrum antibiotics should be stopped and acombination of adequate fluid replacement and oral Prevalence metronidazole is used. Geography Giardiasis Occurs worldwide but most common in the tropics and subtropics. Definition Infection of the gastrointestinal tract by Giardia lamblia a flagellate protozoa. Aetiology The condition is caused by Entamoeba histolytica,trans- Aetiology mission occurs through food and drink contamination Giardia is found worldwide especially in the tropics and or by anal sexual activity. Pathophysiology The amoeba can exist as two forms; a cyst and a tropho- Pathophysiology zoite, only the cysts survive outside the body. Following The organism is excreted in the faeces of infected pa- ingestion the trophozoites emerge in the small intestine tients as cysts. These are ingested, usually in contami- and then pass to the colon where they may invade the nated drinking water. Clinical features r Patients may have a gradual onset of mild intermittent Patients may be asymptomatic carriers or may present diarrhoea and abdominal discomfort. Subsequently 1–2 weeks after ingestion of cysts with diarrhoea, nausea, bloody diarrhoea with mucus and systemic upset may anorexia, abdominal discomfort and distension. A may be steatorrhoea, and if the condition is prolonged fulminating colitis with a low-grade fever and dehy- there may be weight loss. Complications r Aspirates from the duodenum or jejunal biopsy can r Severe haemorrhage may result from erosion into a be used for identification. A 3-day course of metronidazole or a single oral dose of r Progression of fulminant colitis to toxic dilatation tinidazole are highly effective treatments for giardiasis. Prevention is by improved sanitation and precautions r Chronic infection causes fibrosis and stricture forma- with drinking water. Management Management Metronidazole is the drug of choice, large liver abscesses r Ciprofloxacin, chloramphenicol and amoxycillin have require ultrasound guided percutaneous drainage. Enteric fever (typhoid and r Avaccine is available which gives some protection for paratyphoid) up to 3 years. Definition Typhoid (Salmonella typhi) and paratyphoid (Salmon- Botulism ella paratyphi A, B or C)produce a clinically identical disease. Definition Botulism is a serious food poisoning caused by the Gram Aetiology/pathophysiology positive bacillus Clostridium botulinum. Organisms pass The bacteria are soil borne, spores are heat resistant to via the ileum and the lymphatic system to the systemic 100˚C. Some secrete salmonella for over a 1 Food borne botulism in which toxin in the food is year and measurement of Vi agglutinin is used to detect ingested. Clinical features 3 Wound botulism in which the organism is implanted 1 The condition typically runs a course of around 1 into a wound. There is gradual onset of a viral like illness with headache Pathophysiology and fever worsening over 3–4 days. There is initially Toxins are transported via the blood stream to the pe- constipation. Botulinum toxin acts to block 2 Week 2 the patient appears toxic with dehydration, neurotransmission. Patients develop an erythematous maculopapular-blanching Clinical features rash with splenomegaly. The illness starts with nausea and vomiting 12–72 hours 3 During week 3 complications include pneumonia, afteringestingtheorganism. Neurologicalfeaturesresult haemolytic anaemia, meningitis, peripheral neuropa- from neuromuscular blockade: blurred vision, squint thy, acute cholecystitis, osteomyelitis, intestinal perfo- due to lateral rectus muscle weakness, the pupil is fixed ration and haemorrhage. Laryngeal 4 Over the subsequent week there is a gradual return to and pharyngeal paralysis heralds the onset of a gener- normal health. Chapter 4: Gastrointestinal infections 153 Investigations The toxin is demonstrable in the faeces. Intravenous antitoxin and guanidine hydrochlo- ride to reverse neuromuscular blockade has been used. The serovar 0:1 is the major pathogenic strain and Clinical features is divided into two biotypes; classical and the more Theincubationperiodisbetweenafewhoursand1week. Phage typing can be used to but in severe cases there may be watery diarrhoea with examine epidemics to try and see if the observed condi- mucous, termed rice water stool. Serotyping of Biotype: growth on Bacteria somatic O media, and enzyme antigens production Classical Serovar 0:1 Vibrio cholera El Tor Non 0:1 Figure 4. Caseating granulomas and fibrosis may volaemia may be made using clinical indices such as the result in stricture formation and obstructions. Clinical features r In significant volume depletion intravenous saline The presentation depends on the site of infection and should be administered. Patients may present with put should be documented hourly and reviewed with diarrhoea, abdominal pain, alteration of bowel habit, care. Gastric outflow obstruction may result in choice using a solution containing sodium, potas- vomiting and a succussion splash on examination. Clinically gastroin- glucose to facilitate absorption, rice-based polymers testinal tuberculosis may be difficult to distinguish from have been used in place of glucose with some evi- Crohn’s disease. Investigations r Tetracycline or ciprofloxacin can be used to shorten Abdominal ultrasound may demonstrate mesenteric duration and reduce severity of illness.

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