The onset-of-action and plasma half-life varies depending on the route of use purchase 4mg doxazosin fast delivery, rapidly if taken intravenously or smoked compared with when it is snorted buy doxazosin 2mg on-line. Ingestion of stimulant drugs generic doxazosin 1 mg without prescription, such as cocaine or amphetamine, result in acti- vation of the sympathetic nervous system with resulting euphoria followed by irritability, depression, insomnia, and paranoia (Table 12). Tolerance occurs to the psychological effects but not to the effects on the heart. Deaths may occur, most commonly from cardiac dysrhythmias, myo- cardial infarction, agitated delirium, and stroke. Chronic effects include per- 300 Stark and Norfolk Table 12 Effects of Cocaine and Amphetamine Intoxication Initial low dose Euphoria, insomnia, dry mouth, hyperthermia, tachycardia, hypertension, increased respiration, sweating, dilated pupils With increasing dose Irritability, impulsivity, aggressiveness, agitated delirium, paranoia, delusions, seizures foration of the nasal septum and rhinorrhea, and long-term use may result in a range of psychiatric problems and vascular diseases (71). Cocaine produces a physical and psychological dependence, the severity of which will vary depending on the method of administration, being more severe if the drug is smoked or injected than if snorted. Dependence may result in a particular strong craving for the drug, followed by a withdrawal syndrome, or “crash,” with irritability, insomnia, depression, and anxiety on cessation. In conditions of police custody, the depression and inability to sleep may lead to acts of self-harm and suicide, and close supervision may be required, with con- sideration given to prescribing hypnotics and antidepressants. Amphetamine Amphetamine is usually found as a white powder, amphetamine sulphate, and can be taken nasally, orally, or intravenously. Clinical effects are similar to those of cocaine (Table 12), although amphetamine has a longer half-life of 10–15 h, so the duration of euphoria is longer. Alcohol, sedative-hyp- notic drugs, and heroin may be used to reduce the anxiety caused by amphet- amine or, alternatively, amphetamine may be used to reduce the sedative effects of such drugs. Psychological dependence occurs, and psychosis may occur, which resolves when the drug is stopped. Khat Khat consists of the young leaves of the Catha edulis plant; it is usually chewed for its stimulant effect when fresh but may be drunk as an infusion of leaves. In the United Kingdom, it is sold legally (it is illegal in the United States) and is used by Somali populations (72,73). The main component is cathinone, with effects similar to those of amphetamine, resulting in euphoria, Substance Misuse 301 increased alertness, and anorexia (74). Heavy khat consumption may result in mania-like symptoms, paranoia, and an acute schizophrenia-like psychosis, usually resolving within weeks of cessation of use (76,77). Although there is no specific physical withdrawal syndrome, depression, hypersomnia, and loss of energy may occur when khat use is stopped (75). Marijuana Marijuana is the most commonly used illicit drug in the United Kingdom (with 11% of 16–59 years olds having used it in the last year; see ref. There are several forms, including hashish (a resin), herbal cannabis (a green-colored preparation made from the leaves of the plant), and cannabis oil. The onset of effects is reported as being more rapid, and the hallucinogenic properties are heightened. Tolerance develops to many effects of cannabis, including the “high” with chronic use, and an abstinence syndrome has been described with dis- turbed sleep, decreased appetite, restlessness, irritability, and sweating. With- drawal symptoms are usually mild and short-lived, although they may be more severe in heavy regular users (82). Anabolic Steroids Anabolic steroids may be taken orally or intramuscularly by body builders or other individuals who want to enhance their physical appearance. Research has shown that injections of testosterone enanthate increase muscle size and strength, especially when combined with exercise (83). To achieve the desired effect, different steroids are taken in cycles, with rest periods in between, a regime known as “stacking,” or, alternatively, increasing doses of the same ste- roid are taken, a so-called drug pyramid (84). Most of the steroids sold in the United Kingdom are counterfeit rather than produced by legitimate pharmaceu- tical companies. Consequently, they may contain a different steroid from the 302 Stark and Norfolk 302 Substance Misuse 303 one indicated on the bottle, and scant reliance can be placed on the reported dose because they may have little or no steroid in them at all (85). General effects of anabolic steroids (86) include baldness, acne (typi- cally affecting the shoulders and upper back), raised blood pressure and heart rate, fluid retention, and a reduction in high-density lipoprotein cholesterol. Gynecomastia may occur, and the prostate gland may swell, resulting in impaired micturition. Most of these effects are dose dependent and more likely with prolonged administration. While the drug is being taken, there is a significant reduction in testoster- one production by the testes so that sperm output and quality are decreased, and a return to normal can take many months after drug use is stopped. The effect on sex drive is variable, but overall it seems that the sex drive increases at the beginning of a steroid-using cycle, and then decreases to below normal after several weeks of use. Drive may remain below normal levels even after the drug is stopped, until such time as the testes start producing testosterone again. In women, menstrual irregularities are reported, with permanent enlarge- ment of the clitoris. There may also be growth of facial and body hair, male pattern baldness, and decreased breast size. Abuse of sex steroids by recre- ational body builders may be an unrecognized cause of subfertility (88). Liver function tests may show abnormalities that usually return to nor- mal once the drug is stopped. Drug-induced jaundice can be caused by tempo- rarily impaired excretory function, and peliosis hepatitis, in which the liver tissue is replaced by blood-filled cysts, may occur, as can liver tumors (89) and Wilms’ tumor. Initial use may result in stimulatory effects, such as increased confidence, decreased fatigue, heightened motivation, agitation, irritability, and insom- nia, which may progress to argumentative and aggressive behavior and major mood disturbances including depression, mania, and hypomania (90,91). Other Body-Building Drugs Other drugs may be used by body builders (93), including tamoxifen to reduce or prevent gynecomastia; diuretics to counteract the fluid retention caused by anabolic steroids; thyroxine to increase the rate of metabolism, which might theoretically increase the ability of anabolic steroids to boost physical strength (94); and β human chorionic gonadotrophin to alleviate testicular atrophy (95). Nalbuphine (Nubain) is an opioid agonist/antagonist analgesic used for the treat- 304 Stark and Norfolk ment of moderate-to-severe pain, and dependence has been reported associated with anabolic steroid use (96). Furthermore, there has been a case report of a 21-year-old body builder who was admitted after taking excessive amounts of insulin intravenously; apparently, insulin is advertised in body-building magazines as having ana- bolic properties (97). The recreational use of caffeine to toxic levels has been reported in a body builder who presented with a grand mal seizure (98). Clenbuterol, which is a sympathomimetic agonist (used as a oral bronchodila- tor in some European countries but not licensed for human use in the United Kingdom or United States) is said to have an “anabolic-like” effect but at high dose may cause cardiac dysrhythmias, tremor, and serious hypokalemia (99). It has been used as an anesthetic (although it has little analgesic effect), to alleviate narcolepsy, and to treat alcohol and opiate dependence (101). There have been reports of abuse in the United Kingdom and United States within the dance scene and gay clubs and with body builders because it is said to promote slow-wave sleep during which growth hormone is secreted (102). It is available as a color- less, odorless liquid, powder, or a capsule to be taken orally; it is rarely injected. It has a half-life of 30 minutes (103), and effects can last from 45 minutes to 8 h (104). Initial effects include euphoria followed by profound sedation, confu- sion, agitation, amnesia, nausea, vomiting, diarrhea, ataxia, seizures, hypoto- nia, tremor, vertigo and dizziness, bradycardia, hypotension, hypothermia, coma (105), and respiratory collapse. Tolerance and physi- cal dependence after high-dose use can develop with a withdrawal syndrome, which may include insomnia, muscular cramping, tremor, and anxiety (101). A rapid deterioration into delirium may occur in more frequent high-dose dependent users. Withdrawal is not associated with seizures, but if suspected, hospital admission should be considered (108). Ketamine Ketamine is a commercially available anesthetic for intravenous and intra- muscular use. It contains analgesic properties and is available on the street in Substance Misuse 305 powder, tablet, and liquid form; it can be smoked or taken intranasally (“snorted”), orally, intramuscularly, or intravenously (109). The onset of effects depends on the route of administration; when taken orally, effects start within 20 minutes and can last up to 3 hours, whereas given intravenously, effects will be seen within 30 seconds and last about 30 minutes (110). Physical effects may include a cocaine-like “rush,” hypertension, dysrhythmias, nausea, and vomiting, slurred speech, nystagmus, lack of coor- dination, and seizures. On recovery, “emergence phenomena” may occur, with psychological dissociation or out of body (flying or floating) sensations, con- fusion, hallucinations, synesthesia, and depersonalization (112). Such disso- ciative states may result in the individual becoming divorced from reality, and these effects, coupled with possible loss of coordination and pronounced anal- gesia, can result in serious accidents to users.

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Finally buy 2 mg doxazosin visa, salt consumption was highest in Poland and Portugal and lowest in Sweden 4 mg doxazosin amex, Finland and Iceland doxazosin 2mg with visa. The elderly: Research exploring the diets of the elderly indicate that although many younger and non institutionalised members of this group have satisfactory diets many elderly people particularly the older elderly report diets which are deficient in vitamins, too low in energy and have poor nutrient content. This chapter will describe developmental models, cognitive models and the role of weight concern in understanding eating behaviour (see Figure 6. The work was conducted at a time when current feeding policies endorsed a very restricted feeding regime and Davis was interested to examine infants’ responses to a self selected diet. The children were offered a variety of 10 to 12 healthy foods prepared without sugar, salt or seasoning and were free to eat whatever they chose. Her detailed reports from this study showed that the children were able to select a diet consistent with growth and health and were free from any feeding problems. The results from this study generated a theory of ‘the wisdom of the body’ which emphasized the body’s innate food preferences. In line with this, Davis concluded from her data that children have an innate regulatory mechanism and are able to select a healthy diet. She also, however, emphasized that they could only do so as long as healthy food was available and argued that the children’s food preferences changed over time and were modified by experience. Birch, who has extensively studied the developmental aspects of eating behaviour, interpreted Davis’s data to suggest that what was innate was the ‘ability to learn about the consequences of eating [and] to learn to associate food cues with the consequences of ingestion in order to control food intake’ (Birch 1989). Birch therefore emphasized the role of learning and described a developmental systems perspective (e. In line with this analysis, the development of food preferences can be understood in terms of exposure, social learning and associative learning. Exposure Human beings need to consume a variety of foods in order to have a balanced diet and yet show fear and avoidance of novel foodstuffs called neophobia. Young children will therefore show neophobic responses to food but must come to accept and eat foods which may originally appear as threatening. Research has shown that mere exposure to novel foods can change children’s preferences. For example, Birch and Marlin (1982) gave 2-year-old children novel foods over a six-week period. One food was presented 20 times, one 10 times, one 5 times whilst one remained novel. The results showed a direct relationship between exposure and food preference and indicated that a minimum of about 8 to 10 exposures was necessary before preferences began to shift significantly. One hypothesized explanation for the impact of exposure is the ‘learned safety’ view (Kalat and Rozin 1973) which suggests that preference increases because eating the food has not resulted in any negative consequences. This suggestion has been supported by studies which exposed children either to just the sight of food or to both the sight and taste of food. The results showed that looking at novel foods was not sufficient to increase preference and that tasting was necessary (Birch et al. It would seem, however, that these negative consequences must occur within a short period of time after tasting the food as telling children that a novel food is ‘good for you’ has no impact on neophobia whereas telling them that it will taste good does (Pliner and Loewen 1997). The exposure hypothesis is also supported by evidence indicating that neophobia reduces with age (Birch 1989). Social learning Social learning describes the impact of observing other people’s behaviour on one’s own behaviour and is sometimes referred to as ‘modelling’ or ‘observational learning’. An early study explored the impact of ‘social suggestion’ on children’s eating behaviours and arranged to have children observe a series of role models making eating behaviours different to their own (Duncker 1938). The results showed a greater change in the child’s food preference if the model was an older child, a friend or the fictional hero. In another study peer modelling was used to change children’s preference for vegetables (Birch 1980). By the end of the study the children showed a shift in their vegetable preference which persisted at a follow-up assessment several weeks later. The impact of social learning has also been shown in an intervention study designed to change children’s eating behaviour using video based peer modelling (Lowe et al. This series of studies used video material of ‘food dudes’ who were older children enthusiastically consuming refused food which was shown to children with a history of food refusal. The results showed that exposure to the ‘food dudes’ significantly changed the children’s food preferences and specifically increased their consumption of fruit and vegetables. Parental attitudes to food and eating behaviours are also central to the process of social learning. In line with this, Wardle (1995) contended that, ‘Parental attitudes must certainly affect their children indirectly through the foods purchased for and served in the household,. Some evidence indicates that parents do influence their children’s eating behaviour. Parental behaviour and attitudes are therefore central to the process of social learning with research highlighting a positive association between parents’ and children’s diets. For example, Wardle (1995) reported that mothers rated health as more important for their children than for themselves. Alderson and Ogden (1999) similarly reported that whereas mothers were more motivated by calories, cost, time and avail- ability for themselves they rated nutrition and long-term health as more important for their children. In addition, mothers may also differentiate between themselves and their children in their choices of food. For example, Alderson and Ogden (1999) indicated that mothers fed their children more of the less healthy dairy products, breads, cereals and potatoes and fewer of the healthy equivalents to these foods than they ate themselves. Furthermore, this differentiation was greater in dieting mothers suggesting that mothers who restrain their own food intake may feed their children more of the foods that they are denying themselves. A relationship between maternal dieting and eating behaviour is also supported by a study of 197 families with pre-pubescent girls by Birch and Fisher (2000). This study concluded that the best predictors of the daughter’s eating behaviour were the mother’s level of dietary restraint and the mother’s perceptions of the risk of her daughter becoming overweight. In sum, parental behaviours and attitudes may influence those of their children through the mechanisms of social learning. This association, however, may not always be straightforward with parents differentiating between them- selves and their children both in terms of food related motivations and eating behaviour. The role of social learning is also shown by the impact of television and food advertising. For example, after Eyton’s ‘The F plan diet’ was launched by the media in 1982 which recommended a high fibre diet, sales of bran-based cereals rose by 30 per cent, wholewheat bread rose by 10 per cent, wholewheat pasta rose by 70 per cent and baked beans rose by 8 per cent. Egg sales then fell by 50 per cent and by 1989 were still only at 75 per cent of their previous levels (Mintel 1990). The study used interviews, focus groups and an analysis of the content and style of media presentations (MacIntyre et al. The authors concluded that the media has a major impact upon what people eat and how they think about foods. The authors stated, however, that the public do not just passively respond to the media ‘but that they exercise judgement and discretion in how much they incorporate media messages about health and safety into their diets’ (MacIntyre 1998: 249). Further they argued that eating behaviours are limited by personal circumstances such as age, gender, income and family structure and that people actively negotiate their understanding of food within both the micro context (such as their immediate social networks) and the macro social con- texts (such as the food production and information production systems). This study suggests, however, the individuals learn from the media by placing the information being provided within the broader context of their lives. This includes significant others in the immediate environment, particularly parents and the media which offer new information, present role models and illustrate behaviour and attitudes which can be observed and incorporated into the individual’s own behavioural repertoire. Associative learning Associative learning refers to the impact of contingent factors on behaviour. At times these contingent factors can be considered reinforcers in line with operant conditioning. In terms of eating behaviour, research has explored the impact of pairing food cues with aspects of the environment. In particular, food has been paired with a reward, used as the reward and paired with physiological consequences. Rewarding eating behaviour: Some research has examined the effect of rewarding eating behaviour as in ‘if you eat your vegetables I will be pleased with you’.

The diffuse infiltrates on chest X-ray suggest atypical pneumonia buy doxazosin 4mg visa, whereas a lobar pattern tends to occur with streptococcal pneumonia quality 1mg doxazosin. Hypo- natraemia occurs in cases of severe pneumonia and is a poor prognostic factor buy generic doxazosin 4mg. Legionella outbreaks have often been due to infected water tanks in warm climates in institutions such as hotels and hospitals. He needs to receive high concentration of inspired oxygen, and also intravenous fluids to correct his dehydration. These should cover the common community-acquired pneumonias until the pre- cise microbiological diagnosis is obtained and the antibiotics can then be rationalized. Blood cultures should be sent, and blood sent to screen for antibodies to atypical organisms such as Legionella, Mycoplasma, Chlamydia psittaci and influenza. Ten to fourteen days later a further blood sample should be sent and a fourfold rise in antibody titre is evidence of current infection. A faster diag- nosis is made by testing broncheoalveolar lavage fluid, blood and urine for the presence of Legionella antigen. Over the past 10 years she has had previous episodes of loin pain which have occurred on both sides and resolved spontaneously over a few days. Examination of the cardiovascular and respiratory systems is otherwise unremarkable. The palpable abdominal masses in both flanks have the characteristic features of enlarged kidneys. The other principal causes for palpable kidneys are renal cell carcinoma and massive hydronephrosis. Flank pain is the most common symp- tom, and may be caused by cyst rupture, cyst infection or renal calculi. Macroscopic haematuria due to cyst haemorrhage occurs commonly and usually resolves spontaneously. Hypertension occurs early in the course of this disease affecting 60 per cent of patients with normal renal function. The pattern of inher- itance in this family is consistent with an autosomal dominant trait. Ultrasound is the preferred initial screening technique as it is cheap, non-invasive and rapid. For a certain diagnosis, there should be at least three renal cysts with at least one cyst in each kidney. Ultrasound in this patient shows the typical appearance of multiple cysts (black areas) surrounded by thickened walls (Fig. She should be referred to a nephrologist for long-term follow-up of her renal failure, and plans should be made for renal replacement therapy. Clinical trials are starting of vasopressin receptor antagonists which show promise at inhibiting cyst growth. The patient’s children should have their blood pressure checked and later be screened by ultrasound. This gene encodes for the protein polycystin which is a membrane glycoprotein that probably mediates cell–cell and/or cell–matrix interactions. Her proximal interphalangeal joints and metacarpophalangeal joints are swollen and painful with effusions present. Rheumatoid arthritis is a chronic, systemic inflammatory disorder principally affecting joints in a periph- eral symmetrical distribution. The peak incidence is between 35 and 55 years in women and 40 and 60 years in men. The acute presentation may occur over the course of a day and be associated with fever and malaise. More commonly, as in this case, it presents insidiously, and this group has a worse prognosis. Rheumatoid arthritis characteristically affects proximal interphalangeal, metacarpophalangeal and wrist joints in the hands, and metatarsophalangeal joints, ankles, knees and cervical spine. As the disease pro- gresses damage to cartilage, bone and tendons leads to the characteristic deformities of this condition. Extra-articular features include rheumatoid nodules, vasculitis causing cutaneous nodules and digital gangrene, scleritis, pleural effusions, diffuse pulmonary fibrosis, pul- monary nodules, obliterative bronchiolitis, pericarditis and splenomegaly (Felty’s syn- drome). In patients with lond-standing rheumatoid arthritis, renal infiltration by amyloid may occur. Differential diagnosis of an acute symmetrical polyarthritis • Osteoarthritis: characteristically affects the distal interphalangeal as well as proximal interphalangeal and first metacarpophalangeal joints. These usually cause an asymmetrical arthritis affecting medium and larger joints as well as the sacroiliac and distal interphalangeal joints. This patient should be referred to a rheumatologist for further investigation and manage- ment. If there has been joint damage, the X-rays will show subluxation, juxta-articular osteoporosis, loss of joint space and bony erosions. A common site for erosions to be found in early rheumatoid arthritis is the fifth metatarso- phalangeal joint (arrowed in Fig. The pain settled for a period of 6 months but it has returned over the last 10 months. She describes it as a tight or gripping pain which lasts for anything from 5 to 30 min at a time. It can come on at any time, and is often related to exercise but it has occurred at rest on some occasions, particularly in the evenings. It makes her stop whatever she is doing and she often feels faint or dizzy with the pain. Detailed questioning about the palpitations indicates that they are a sensation of a strong but steady heart beat. In her previous medical history she had her appendix removed at the age of 15 years. At the age of 30 years she was investigated for an irregular bowel habit and abdominal pain but no specific diagnosis was arrived at. Two years ago she visited a chemist and had her cholesterol level measured; the result was 4. In her family history her grandfather died of a myocardial infarction, a year previously, aged 77 years. Examination On examination, she has a blood pressure of 102/65 mmHg and pulse of 78/min which is reg- ular. There is some tenderness on the left side of the chest, to the left of the sternum and in the left submammary area. On the basis of the information given here it would be reasonable to explore her anxieties and to reassure the patient that this is very unlikely to represent coronary artery disease and to assess subsequently the effects of that reassurance. It may well be that she is anxious about the death of her grandfather from ischaemic heart disease. From a risk point of view her grandfather’s death at the age of 77 with no other affected relatives is not a rele- vant risk factor. She has expressed anxiety already by having the cholesterol measured (and found to be normal). She has a history which is suspicious of irritable bowel syndrome with persistent pain, irregular bowel habit and normal investigations. Ischaemic chest pain is usually central and generally reproducible with the same stimuli. The associated shortness of breath may reflect overventilation coming on with the pain and giving her dizziness and palpitations. The characteristics of the pain and associated shortness of breath should be explored fur- ther. Asthma can sometimes be described as tightness or pain in the chest, and she has sea- sonal rhinitis and a family history of asthma. Gastrointestinal causes of pain such as reflux oesophagitis are unlikely in view of the site and relationship on occasions to exercise.

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If the detainee does not agree purchase doxazosin 4 mg with visa, then the doctor must decide whether withholding relevant details will endanger the lives or health of those working within custody or others with whom they may have had close contact (whether or not deliberate) buy generic doxazosin 1mg on line. Adopting a universal approach with all detainees will decrease the risk to staff of acquiring such diseases and will help to stop unnecessary overreac- tion and unjustified disclosure of sensitive information buy doxazosin 4mg amex. For violent or sexual assault victims, a more open-minded approach is needed (see also Chapter 3). If the assailant is known, then it may be possible to make an informed assess- ment of the risk of certain diseases by ascertaining his or her lifestyle. This chapter highlights the most common infections encountered by the forensic physician. It dispels “urban myths” and provides a sensible approach for achiev- ing effective management. Forensic physicians or other health care professionals should wash their hands before and after contact with each detainee or victim. Police officers should be encouraged to wash their hands after exposure to body fluids or excreta. All staff should wear gloves when exposure to body fluids, mucous membranes, or nonintact skin is likely. Gloves should also be worn when clean- ing up body fluids or handling clinical waste, including contaminated laun- dry. Single-use gloves should only be used and must conform to the requirements of European Standard 455 or equivalent (1–3). A synthetic alter- native conforming to the same standards should also be available for those who are allergic to latex. All staff should cover any fresh wounds (<24 hours old), open skin le- sions, or breaks in exposed skin with a waterproof dressing. Gloves cannot prevent percutaneous injury but may reduce the chance of acquiring a blood- borne viral infection by limiting the volume of blood inoculated. Gloves should only be worn when taking blood, providing this does not reduce manual dex- terity and therefore increase the risk of accidental percutaneous injury. Infectious Diseases 237 Ideally, a designated person should be allocated to ensure that the clini- cal room is kept clean and that Sharps containers and clinical waste bags are removed regularly. After use, the clinical waste should be double- bagged and sealed with hazard tape. The bags should be placed in a desig- nated waste disposal (preferably outside the building) and removed by a professional company. When cells are contaminated with body fluids, a professional cleaning company should be called to attend as soon as possible. Sharps Awareness There is a legal requirement in the United Kingdom under the Environ- mental Protection Act (1990) and the Control of Substances Hazardous to Health Regulations 1994 to dispose of sharps in an approved container. In cus- tody, where Sharps containers are transported off site, they must be of an approved type. In the United Kingdom, such a requirement is contained within the Carriage of Dangerous Goods (Classification, Packaging and Labelling) and Use of Transportable Pressure Receptacles Regulations 1996. Further precautions include wearing gloves when handling Sharps and never bending, breaking, or resheathing needles before disposal. Sharps bins should never be overfilled, left on the floor, or placed above the eye level of the smallest member of staff. Contaminated Bedding Any bedding that is visibly stained with body fluids should be handled with gloves. Laundering with a detergent at a minimum temperature of 71°C (160° F) or at a lower temperature (22–50°C) with water containing detergent and 50–150 ppm of chlorine bleach. Dry cleaning at elevated temperatures/dry cleaning at cold temperatures followed by steam pressing. Other Measures It is not necessary for staff to wear masks or protective eyewear in the custodial setting because the risk of infection is low. However, single-use eye- 238 Nicholson wash should be available in the clinical room or contained in other first aid kits located within the police station in case of accidental exposure. Forensic physicians working for the Metropolitan Police in London can refer to the “Good Practice Guidelines” (4). It is also prudent to prearrange a system of referral with the nearest hospi- tal that has an accident and emergency department, a genitourinary depart- ment, and access to a specialist. The latter may be a consultant in virology, microbiology, infectious diseases, or genitourinary medicine. Similar guid- ance in the United States can be found in the Guideline for Infection Control in Health Care Personnel (5). Most exposures to staff usually result from a failure to follow accepted practice; however, accidents can happen no matter how much care is taken. All forensic physicians and other health care professionals working in custody should understand what constitutes a risk. This involves taking a detailed history of the incident, including the type of exposure, the body fluids involved, and when the incident occurred. This information can help to allay unnecessary anxiety from the outset and ensures that the victim is referred, if appropriate, to the designated hospital at the earliest opportunity. Knowledge of precise treatment protocols is not required, but it is helpful to be able to explain to the victim what to expect. For example, he or she will be asked to provide a voluntary baseline blood sample for stor- age and numerous follow-up samples for testing depending on the nature of the exposure. Occasionally, it may be necessary for samples to be obtained as long as 6 mo after the incident. Sexual assault victims should ideally be referred to specialist centers, if available. A police station should be used only as a last resort because the environment is often hostile and there is no ready access to the necessary treat- ment and ongoing management (see Chapter 3). For ease of understanding, the infections discussed in this chapter are classified accord- Infectious Diseases 239 ing to their primary route (i. The degree of risk varies with the virus concerned and is discussed under the relevant sections. Figure 1 illustrates the immediate management after a percutaneous injury, mucocutaneous exposure, or exposure through contamination of fresh cuts or breaks in the skin. Although 135 countries had achieved this goal by the end of 2001, the poorest countries—often the ones with the highest prevalence—have been unable to afford it. In particular these include China, the Indian subcontinent, and Sub-Saharan Africa. Typical symptoms include malaise, anorexia, nausea, mild fever, and abdominal discomfort and may last from 2 days to 3 weeks before the insidious onset of jaundice. Joint pain and skin rashes may also occur as a result of immune complex formation. After acute infection, approx 1 in 300 patients develop liver failure, which may result in death. Chronic infection develops in approx 90% of neonates, approx 50% of children, and between 5 and 10% of adults. Neonates and children are usually Infectious Diseases 241 Table 1 Prevalence of Chronic Hepatitis B • Blood-doning population <1% • Intravenous drug users 10–15% • Homosexual/bisexuals 10–15% • Institutionalized patients no data available • People from high-risk endemic areas up to 30% of the population are carriers, (e. Approximately 15–25% of chronically infected individuals (depend- ing on age of acquisition) will develop cirrhosis over a number of years. This may also result in liver failure or other serious complications, including hepa- tocellular carcinoma, though the latter is rare. The degree of infectivity depends on the stage of disease and the markers present Table 2. Evidence has shown that the virus may also be spread among members of a family through close household contact, such as through kissing and shar- ing toothbrushes, razors, bath towels, etc. This route of transmission probably applies to institutionalized patients, but there are no available data. Vaccine is given to the neonate ideally within the first 12 hours of birth and at least two more doses are given at designated intervals. How- ever, the practicalities of administering a vaccine that has to be stored at the correct temperature in places with limited access to medical care means that there is a significant failure of vaccine uptake and response. The routine schedule consists of three doses of the vaccine given at 0, 1, and 6 months. In the United States, if an initial adequate response has been achieved, then no further doses of vaccine are considered necessary. Vaccine administration after exposure varies according to the timing of the incident, the degree of risk involved, and whether the individual has already been partly or fully vaccinated.

People suffering from anorexia often must be hospi- nal of Psychology (July 1995): 477 4 mg doxazosin visa. Treatment and cure for anorexia are possible through skilled psychiatric intervention that includes medical evaluation buy generic doxazosin 4 mg, psychotherapy for the individual and family group purchase doxazosin 1mg, nutritional counseling, and possibly medication and/or hospitalization. With treatment and the passage of time, about 70 percent of anorexics eventually recover and are able to maintain a normal body weight. The American Anorexia and Bulimia Association is the principal and oldest national non-profit organization working for the prevention, treatment, and cure of eating disorders. It also organizes a referral network which in- cludes educational programs and public information ma- terials, professional services and outpatient programs, patient and parent support groups, and training of recov- ered patients as support group facilitators. American Psychiatric Association estimates that mor- National Association of Anorexia Nervosa and Associated Dis- tality rates for anorexia may be as high as 5 to 18 percent. The peak times of onset are ages 12 to 13 and Medications used to treat depression. In adults with resistant depression,several types of slowly adjusting the dose of the drug. Antisocial behavior can be broken down into two components: the presence of antisocial (i. Some, however, may exhibit Several studies have reported 70-90% response rate to low levels of both types of behaviors; for example, the fluoxetine or sertraline for the treatment of adolescents withdrawn, thoughtful child. High levels of antisocial with major depressive disorder, but the results of these behavior are considered a clinical disorder. Young chil- studies are not conclusive because they have methodologi- dren may exhibit hostility towards authority, and be di- cal limitations. A recent, large, well-performed investiga- agnosed with oppositional-defiant disorder. Older chil- tion showed that fluoxetine was more effective for the dren may lie, steal, or engage in violent behaviors, and treatment of depressed children and adolescents than a be diagnosed with conduct disorder. Despite the significant response to fluoxetine, professionals agree, and rising rates of serious school many patients had only partial improvement. The most common side effects in- Thirty to 70% of childhood psychiatric admissons are clude nausea, stomachache, diarrhea, headaches, mild for disruptive behavior disorders, and diagnoses of be- tremors, sweating, sleep disturbance, sedation, restless- havior disorders are increasing overall. A small percent- ness, lack of appetite, decreased weight, vivid dreams, age of antisocial children grow up to become adults with and sexual dysfunction (inability to have an orgasm or antisocial personality disorder, and a greater propor- delayed ejaculation). Most of these side effects are tem- tion suffer from the social, academic, and occupational porary and may be diminished by reducing the dose or failures resulting from their antisocial behavior. Attention The most important goals of treating antisocial be- deficit/hyperactivity disorder is highly correlated with havior are to measure and describe the individual child’s antisocial behavior. A child may exhibit antisocial be- or adolescent’s actual problem behaviors and to effective- havior in response to a specific stressor (such as the ly teach him or her the positive behaviors that should be death of a parent or a divorce) for a limited period of adopted instead. In severe cases, medication will be ad- time, but this is not considered a psychiatric condition. Children who experience explo- ders have an increased risk of accidents, school failure, sive rage respond well to medication. Ideally, an interdis- early alcohol and substance use, suicide, and criminal ciplinary team of teachers, social workers, and guidance behavior. The elements of a moderate to severely antiso- counselors will work with parents or caregivers to pro- cial personality are established as early as kindergarten. In many cases, parents themselves need is, the degree to which they value, and are motivated by, intensive training on modeling and reinforcing appropri- approval from others. Yet underneath their tough exterior ate behaviors in their child, as well as in providing appro- antisocial children have low self-esteem. A variety of methods may be employed to deliver A salient characteristic of antisocial children and social skills training, but especially with diagnosed anti- adolescents is that they appear to have no feelings. Be- social disorders, the most effective methods are systemic sides showing no care for others’ feelings or remorse for therapies which address communication skills among the hurting others, they tend to demonstrate none of their whole family or within a peer group of other antisocial own feelings except anger and hostility, and even these children or adolescents. These probably work best be- are communicated by their aggressive acts and not neces- cause they entail actually developing (or redeveloping) sarily expressed through affect. One analysis of antiso- positive relationships between the child or adolescent cial behavior is that it is a defense mechanism that helps and other people. Methods used in social skills training the child to avoid painful feelings, or else to avoid the include modeling, role playing, corrective feedback, and anxiety caused by lack of control over the environment. Regardless of the method Antisocial behavior may also be a direct attempt to used, the child’s level of cognitive and emotional devel- alter the environment. Ado- that negative behaviors are reinforced during childhood lescents capable of learning communication and prob- by parents, caregivers, or peers. In one formulation, a lem-solving skills are more likely to improve their rela- child’s negative behavior (e. Few institutions can afford the will apply the learned behavior at school, and a vicious comprehensiveness and intensity of services required to cycle sets in: he or she is rejected, becomes angry and at- support and change a child’s whole system of behavior; tempts to force his will or assert his pride, and is then in most cases, for various reasons, treatment is terminated further rejected by the very peers from whom he might (usually by the client) long before it is completed. Schools “mutual avoidance” sets in with the parent(s), as each are frequently the first to address behavior problems, and party avoids the negative behaviors of the other. Conse- regular classroom teachers only spend a limited amount quently, the child receives little care or supervision and, of time with individual students. Special education especially during adolescence, is free to join peers who teachers and counselors have a better chance at instituting have similarly learned antisocial means of expression. The fact that peer groups have such a strong influence on behavior The adult with antisocial personality disorder dis- suggests that schools that employ collaborative learning plays at least three of the following behaviors: and the mainstreaming of antisocial students with regu- •Fails to conform to social norms, as indicated by fre- lar students may prove most beneficial to the antisocial quently performing illegal acts, and pursuing illegal oc- child. By judi- • Is deceitful and manipulative of others, often in order ciously dividing the classroom into groups and explicitly to obtain money, sex, or drugs. See also Antisocial personality disorder; Conduct dis- order; Oppositional-defiant disorder; Peer acceptance • Exhibits reckless disregard for safety of self or others, misusing motor vehicles or playing with fire. Further Reading • Is consistently irresponsible, failing to find or sustain Evans, W. The Behavior Management Handbook: Setting An individual diagnosed with antisocial personality Up Effective Behavior Management Systems. Boston: disorder will demonstrate few of his or her own feelings Allyn and Bacon, 1989. New York: Free Press, ity disorder with abuse, either physical or sexual, during 1965. Those with a parent with an anti- tion of Explanations of Delinquent Behavior, 2nd ed. Understanding Black Adolescent Male Vio- substance abuser, or have an extensive criminal record. Afrikan World In- Antisocial personality disorder is associated with low so- fosystems, 1992. Treatment Antisocial personality disorder is highly unrespon- Antisocial personality sive to any form of treatment. Although there are med- disorder ications available that could quell some of the symptoms A behavior disorder developed by a small percent- of the disorder, noncompliance or abuse of the drugs pre- age of children with conduct disorder whose be- vents their widespread use. Also ment programs are long-term, structured residential set- known as sociopathy or psychopathy. Some form of dynamic About 3% of males and 1% of females develop anti- psychotherapy is usually given along with the behavior social personality disorder, which is essentially the adult modification. Anxious few relationships in his or her life and is unable to trust, feelings interfere with a person’s ability to carry out nor- fantasize, feel, or learn. Many people experience stage opportunity to establish positive relationships with as fright—the fear of speaking in public in front of large many people as possible and be encouraged to join self- groups of people. There is little, if any, real danger posed help groups or prosocial reform organizations. Sigmund Freud described neurotic anxi- positional-defiant disorder; Peer acceptance ety as a danger signal. In his id-ego-superego scheme of Further Reading human behavior, anxiety occurs when unconscious sex- Cleckley, Hervey M. New York: ual or aggressive tendencies conflict with physical or New American Library; St. New York: a change in heart rate, trembling, dizziness, and tension, Tavistock Publications, 1984.

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If the blade is double- edged 2mg doxazosin fast delivery, such as that of a dagger discount 2mg doxazosin otc, the extremities of the wound tend to be equally pointed generic doxazosin 1 mg without prescription. A stab wound from a single-edged blade, such as a kitchen knife, will usually have one extremity rounded, squared-off, or fish-tailed (caused by the noncutting back of the blade). When blunt weapons are used—a pair of scissors, for example—the wound tends to be more rounded or oval, with bruising of its margins (see Fig. Scissor wounds can sometimes have a cross-shape caused by the blade screws or rivets. Notched wounds are often caused by the blade of the weapon being partially withdrawn and then rein- troduced into the wound or twisted during penetration. It is rarely possible from an inspection of the skin wound alone to com- ment usefully on the width of the blade because the skin retracts and the knife is unlikely to have been introduced and removed perfectly perpendicularly. Deliberate Self-Harm Deliberate self-harm refers to any attempt by an individual to harm him- self or herself. When assessing injuries, it is important to understand which factors may indicate the possibility that an injury was caused by deliberate Injury Assessment 143 Table 4 Indicators of Possible Deliberate Self-Harm Injuries • Must be on an area of body accessible to the person to injure themselves. Individuals injure themselves for numerous reasons, including psy- chiatric illness and others, such as attempting to imply events took place that did not or for motives of gain. Self-inflicted injuries have several characteris- tics, which are not diagnostic but that together may give an indication of self- infliction. Table 4 lists features that may assist in the recognition or suspicion that cuts or other injury, such as scratches, are self-inflicted—all or some may be present—their absence does not preclude self-infliction nor does their pres- ence necessarily imply self-infliction (2). As with all injuries within the forensic setting it is essential in these nonfatal cases that the initial appear- ances of the injuries be accurately described and the wounds photographed. This is particularly important because subsequent surgical treatment may dis- tort or completely obliterate the wound characteristics. Furthermore, any frag- ments, bullets, or pellets found within the wounds must be carefully removed and handed over to the appropriate authorities. Smooth-Bore Weapons Shotguns, which fire a large number of small projectiles, such as lead shot, are the most common type of smooth-bore weapons. They are commonly used in sporting and agricultural activities and may be either single or double- barreled. The ammunition for these weapons consists of a plastic or cardboard cartridge case with a brass base containing a percussion cap. Inside the main part of the cartridge is a layer of propellant, plastic, felt, or cardboard wads and a mass of pellets (lead shot of variable size) (see Fig. In addition to the pellets, the wads and/or cards may contribute to the appearance of the wounds and may be important in estimating range and possible direction. Rifled Weapons Rifled weapons are characterized by having parallel spiral projecting ridges (or lands) extending down the interior of the barrel from the breach to the muzzle. The rifling also leaves characteristic scratches and rifling marks that are unique to that weapon on the bullet surface. There are three common types of rifled weapons: the revolver, the pistol, and the rifle. The Injury Assessment 145 revolver, which tends to have a low muzzle velocity of 150 m/s, is a short- barreled weapon with its ammunition held in a metal drum, which rotates each time the trigger is released. In the self-loading pistol, often called “semi-automatic” or erroneously “automatic,” the ammunition is held in a metal clip-type maga- zine under the breach. Each time the trigger is pulled, the bullet in the breach is fired, the spent cartridge case is ejected from the weapon, and a spring mecha- nism pushes up the next live bullet into the breach ready to be fired. The rifle is a long-barreled shoulder weapon capable of firing bullets with velocities up to 1500 m/s. Most military rifles are “automatic,” allowing the weapon to continue to fire while the trigger is depressed until the magazine is empty; thus, they are capable of discharging multiple rounds within seconds. Shotgun Wounds When a shotgun is discharged, the lead shot emerges from the muzzle as a solid mass and then progressively diverges in a cone shape as the distance from the weapon increases. The pellets are often accompanied by particles of unburned powder, flame, smoke, gases, wads, and cards, which may all affect the appearance of the entrance wound and are dependent on the range of fire. Both the estimated range and the site of the wound are crucial factors in deter- mining whether the wound could have been self-inflicted. If the wound has been sustained through clothing, then important resi- dues may be found on the clothing if it is submitted for forensic examination. It is absolutely essential that the advice of the forensic science team and crime scene investigator is sought when retrieving such evidence. When clothing is being cut off in the hospital, staff should avoid cutting through any apparent holes. The entrance wound is usually a fairly neat circular hole, the margins of which may be bruised or abraded resulting from impact with the muzzle. In the case of a double-barreled weapon, the circular abraded imprint of the nonfiring muzzle may be clearly seen adjacent to the contact wound. The wound margins and the tissues within the base of the wound are usually blackened by smoke and may show signs of burning owing to the effect of flame. Because the gases from the discharge are forced into the wound, there may be subsid- iary lacerations at the wound margin, giving it a stellate-like shape. This is seen particularly where the muzzle contact against the skin is tight and the skin is closely applied to underlying bone, such as in the scalp. Carbon mon- oxide contained within the gases may cause the surrounding skin and soft Injury Assessment 145 revolver, which tends to have a low muzzle velocity of 150 m/s, is a short- barreled weapon with its ammunition held in a metal drum, which rotates each time the trigger is released. In the self-loading pistol, often called “semi-automatic” or erroneously “automatic,” the ammunition is held in a metal clip-type maga- zine under the breach. Each time the trigger is pulled, the bullet in the breach is fired, the spent cartridge case is ejected from the weapon, and a spring mecha- nism pushes up the next live bullet into the breach ready to be fired. The rifle is a long-barreled shoulder weapon capable of firing bullets with velocities up to 1500 m/s. Most military rifles are “automatic,” allowing the weapon to continue to fire while the trigger is depressed until the magazine is empty; thus, they are capable of discharging multiple rounds within seconds. Shotgun Wounds When a shotgun is discharged, the lead shot emerges from the muzzle as a solid mass and then progressively diverges in a cone shape as the distance from the weapon increases. The pellets are often accompanied by particles of unburned powder, flame, smoke, gases, wads, and cards, which may all affect the appearance of the entrance wound and are dependent on the range of fire. Both the estimated range and the site of the wound are crucial factors in deter- mining whether the wound could have been self-inflicted. If the wound has been sustained through clothing, then important resi- dues may be found on the clothing if it is submitted for forensic examination. It is absolutely essential that the advice of the forensic science team and crime scene investigator is sought when retrieving such evidence. When clothing is being cut off in the hospital, staff should avoid cutting through any apparent holes. The entrance wound is usually a fairly neat circular hole, the margins of which may be bruised or abraded resulting from impact with the muzzle. In the case of a double-barreled weapon, the circular abraded imprint of the nonfiring muzzle may be clearly seen adjacent to the contact wound. The wound margins and the tissues within the base of the wound are usually blackened by smoke and may show signs of burning owing to the effect of flame. Because the gases from the discharge are forced into the wound, there may be subsid- iary lacerations at the wound margin, giving it a stellate-like shape. This is seen particularly where the muzzle contact against the skin is tight and the skin is closely applied to underlying bone, such as in the scalp. Carbon mon- oxide contained within the gases may cause the surrounding skin and soft 146 Payne-James et al. Con- tact wounds to the head are particularly severe, usually with bursting ruptures of the scalp and face, multiple explosive fractures of the skull, and extrusion or partial extrusion of the underlying brain. Most contact wounds of the head are suicidal in nature, with the temple, mouth, and underchin being the sites of election. In these types of wounds, which are usually rapidly fatal, fragments of scalp, skull, and brain tissue may be dispersed over a wide area. At close, noncontact range with the muzzle up to about 15 cm (6 in) from the skin, the entrance wound is still usually a single circular or oval hole with possible burning and blackening of its margins from flame, smoke, and unburned powder. Blackening resulting from smoke is rarely seen beyond approx 20 cm; tattooing from powder usually only extends to approx 1 m. Up to approx 1 m they are still traveling as a compact mass, but between approx 1–3 m, the pellets start to scatter and cause variable numbers of individual satellite punc- ture wounds surrounding a larger central hole.

The proteins form the head buy generic doxazosin 2mg on-line, tail buy 1 mg doxazosin mastercard, and other morphological elements purchase doxazosin 4 mg mastercard, the function of which is to protect the phage genome. This element bears the genetic information, the structural genes for the structural proteins as well as for other proteins (enzymes) re- quired to produce new phage particles. Attachment to cell surface involving specific interactions be- tween a phage protein at the end of the tail and a bacterial receptor. Lysis occurs by a phage-encoded murein hydrolase, which gains access to the murein through membrane channels 3 formed by the phage-en- coded protein holin. Enzymatic penetration of the wall by the tail tube tip and injection of the nucleic acid through the tail tube. Beginning with synthesis of early proteins (zero to two minutes after injection), e. Then follows transcription of the late genes that code for the structural proteins of the head and tail. The new phage particles are assembled in a maturation process toward the end of the reproduction cycle. This step usually follows the lysis of the host cell with the help of murein hydrolase coded bya phage gene that destroys the cell wall (Fig. Depending on the phage species and milieu conditions, a phage reproduction cycle takes from 20 to 60 minutes. This is called the latency period, and can be considered as analogous to the generation time of bacteria. Depending on the phage species, an infected cell releases from 20 to several hundred new phages, which number defines the burst size. In view of this fact, one might wonder how any bacteria have survived in nature at all. It is important not to forget that cell population density is a major factor determining the probability of finding a host cell in the first place and that such densities are relatively small in nature. Another aspect is that only a small proportion of phages reproduce solely by means of these lytic or vegetative processes. Following injection of the phage genome, it is integrated into the chromosome by means of region-spe- cific recombination employing an integrase. Cells carrying a prophage are called lysogenic because they contain the genetic information for lysis. It prevents immediate host cell lysis, but also ensures that the phage genome replicates concurrently with host cell reproduction. Lysogenic conversion is when the phage genome lysogenizing a cell bears a gene (or several genes) that codes for bacterial rather than viral processes. Genes localized on phage genomes include the gene for diphtheria toxin, the gene for the pyrogenic toxins of group A streptococci and the cholera toxin gene. Ad- ministration of suitable phage mixtures in therapy and prevention of gastrointestinal infections. Recognition of the bacterial strain responsible for an epidemic, making it possible to follow up the chain of infection and identify the infection sources. The Principles of Antibiotic Therapy 187 The Principles of Antibiotic Therapy & Specific antibacterial therapy refers to treatment of infections with anti- infective agents directed against the infecting pathogen. The most important group of anti-infective agents are the antibiotics, which are products of fungi and bacteria (Streptomycetes). Anti-infective agents are categorized as having a broad, narrow, or medium spectrum of action. The efficacy, or effectiveness, of a substance refers to its bactericidal or bacteriostatic effect. Under the influence of sulfonamides and trimethoprim, bacteria do not synthesize sufficient amounts of tetrahydrofolic acid. Due to their genetic variability, bacteria may devel- op resistance to specific anti-infective agents. The most important resistance mechanisms are: inactivating enzymes, resistant target molecules, reduced influx, increased efflux. Resistant strains (problematic bacteria) occur fre- quently among hospital flora, mainly Enterobacteriaceae, pseudomonads, staphylococci, and enterococci. The disk test is a semiquantitative test used to classify the test bacteria as resistant or susceptible. In combination therapies it must be remembered that the interactions of two or more antibiotics can give rise to an antagonistic effect. Surgical chemoprophylaxis must be administered as a short-term anti- microbial treatment only. One feature of these pharmaceuticals is “selective toxicity,” that is, they act upon bacteria at very low concentration levels without causing damage to the macroorganism. These natural substances are produced by fungi or bacteria (usually Streptomycetes). The term “anti- biotic” is often used in medical contexts to refer to all antibacterial pharma- ceuticals, not just to antibiotics in this narrower sense. The most important groups (cephalosporins, penicillins, 4-quinolones, macrolides, tetracyclines) are in bold print. Pseudomonas; labile against Gram-positive and Gram-negative penicillinases temocillin (6-a-methoxy No effect against Pseudomonas; highly stable in the ticarcillin) presence of betalactamases Acylureidopenicillins azlocillin, mezlocillin, Effective against Enterobacteriaceae and piperacillin, apalcillin Pseudomonas; despite lability against beta- lactamases active against many enzyme-producing strains due to good penetration and high levels of sensitivity of the target molecules Penems Penicillins with a double bond in the second ring system A carbapenem (C atom instead of sulfur in second N-formimidoyl thienamycin ring); very broad spectrum and high level of (imipenem = activity against Gram-positive and Gram-negative N-F-thienamycin + bacteria, including anaerobes; frequently effective cilastatin) against Enterobacteriaceae and Pseudomonas with resistance to the cephalosporins of Group 3b; inactivated by renal enzymes; is therefore administered in combination with the enzyme inhibitor cilastatin Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Sulfones dapsone diaminodiphenylsulfone; for therapy of leprosy Tetracyclines doxycycline tetracycline, Broad spectrum including all bacteria, chlamydias, oxytetracycline, and rickettsias; resistance frequent; dental deposits rolitetracycline, minocycline in small children Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Most, however, have broad spectra like tetracyclines, which affect all eubacteria. Many substances can develop both forms of efficacy depending on their concentration, the type of organism, and the growth phase. After the anti-infective agent is no longer present, the bacterial cells not killed require a recovery phase before they can reproduce again. A bacteriostatic agent alone can never completely eliminate pathogenic bacteria from the body’s tissues. In tissues in which this defense system is inefficient (endocardium), in the middle of a purulent lesion where no functional pha- gocytes are present, or in immunocompromised patients, bactericidal sub- stances must be required. The clinical value of knowing whether an antibac- terial drug is bacteriostatic or bactericidal is readily apparent. All of the bacteria from an infection focus cannot be eliminated without support from the body’s immune defense system. A bacterial population always includes several cells with phenotypic resistance that is not geno- typically founded. These are the so-called persisters, which occur in in-vitro cultures at frequencies ranging from 1:106 to 1:108 (Fig. The cause of such persistence is usually a specific metabolic property of these bacteria that prevents bactericidal substances from killing them. Infections with L-forms show a special type of persistence when treated with antibiotics that block murein synthesis (p. The Principles of Antibiotic Therapy 197 Efficacy of Selected AntI-Infective Agents Betalactams Amino- glycosides Sulfonamides Tetracyclines Betalactams, 3 aminoglycosi- des Persisters Time (hours) Fig. Betalactams are bactericidal only during the bacterial cell division phase, whereas aminoglycosides show this activity in all growth phases. Some cells in every culture (so-called persisters) are phenotypically (but not genotypically) resistant to the bactericidal effects of anti-infective agents. The combination of sulfamethoxazole and trimethoprim (cotrimoxazole) results in a po- tentiated efficacy. They probably hold in similar form for other betalactams and other bacteria as well. These enzymes create gaps in the murein sac- culus while the bacterium is growing, these gaps are then filled in with new murein materi- al. Bacteria the growth of which is inhibited, but which are not lysed, show betalactam toler- ance (bacteriostatic, but not bactericidal ef- fects). The biosynthesis of bacterial proteins differs in detail from that observed in eukaryotes, per- mitting a selective inhibition by antibiotics. The special proliferation forms observed in nutrient broth and nutrient agar give an experienced bacteriologist sufficient informa- tion for an initial classification of the pathogen so that identifying reactions can then be tested with some degree of specificity. This can be achieved by adding suitable reduction agents to the nutrient broth or by proliferating the cultures under a gas atmosphere from which most of the oxygen has been removed by physical, chemical, or biological means.

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