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Direct economic impacts are felt by livestock owners without trypanotolerant breeds who suffer significant constraints on production through morbidity glycomet 500mg low price, mortality and impaired fertility glycomet 500 mg amex. Indirectly, the disease affects crop producers who rely on livestock (draught oxen) to pull farm machinery and produce manure. Farmers are also hindered by perceived risks of the disease, for example, on tsetse fly-infected ground they may reduce their numbers of livestock or exclude livestock from infested regions all together. In Africa, 7 million hectares of suitable grazing land are left ungrazed due to trypanosomiasis. However, the benefits for wildlife balance this economically where tourism and other forms of wildlife utilisation exist. Implementing prevention and control measures using trypanocidal drugs represents an additional expense. Measuring the costs of African animal trypanosomosis, the potential benefits of control and returns to research. Spatial distribution of African animal trypanosomiasis in Suba and Teso districts in western Kenya. A field guide for the diagnosis, treatment and prevention of African animal trypanosomiasis. The disease has become a major cause of amphibian mortality and morbidity worldwide over the last decade, leading to catastrophic declines in populations in North America, South America, Central America, Europe, Australia and the Caribbean. The disease does not affect livestock or humans, their only role being as carriers of the fungus on e. Species affected Most species of amphibian, although its severity can range from no clinical signs to acute mortality, depending on the amphibian species, the infectious dose, the strain of fungus and the environmental conditions. The disease has been described in a wide variety of anurans (frogs and toads) and caudates (salamanders and newts), but not yet in caecilians. Geographic distribution The disease occurs in every continent where there are amphibians i. This disease has occurred at varying altitudes and degrees of humidity in areas of standing water. How is the disease The fungus has two life stages, an intra-cellular sporangium and a free- transmitted to animals? Zoospores are released from the skin (or mouthparts) of an infected animal and move through the water, or remain in a damp environment, until they come into contact with another (or the same) amphibian, which they then infect. How does the disease Movement of amphibians or spread of contaminated material (including water, spread between groups mud or fomites) between groups. Some of the most common signs in individuals are reddened or otherwise discoloured skin, excessive shedding of skin, abnormal postures, such as a preference for keeping the skin of the belly away from the ground, unnatural behaviours such as a nocturnal species that suddenly becomes active during the day, or seizures. Many of these signs are said to be “non-specific” and many different amphibian diseases have signs similar to those of chytridiomycosis. Recommended action if Contact and seek assistance from appropriate animal health professionals. Diagnosis Diagnosis is carried out by taking samples using swabs: swabbing the skin of the back legs, drink patch (i. The skin of dead amphibians can be similarly swabbed and freshly-dead specimens can be submitted for post mortem examination, including histology, in specialist laboratories. Before collecting or sending any samples from animals with a suspected disease, the proper authorities should be contacted. Samples should only be sent under secure conditions and to authorised or suitably qualified laboratories to prevent the spread of the disease. Although the fungus that causes amphibian chytridiomycosis is not known to be zoonotic, routine hygiene precautions are recommended when handling animals. Also, suitable precautions must be taken to avoid cross-contamination of samples or cross- infection of animals. Livestock The disease does not affect livestock, however, ensure that livestock moving between sites (especially those travelling from known infected sites) do not mechanically spread infection by carrying infected material on their feet or coats. Use foot baths and leave animals in a dry area after the bath for their feet to fully dry before transport. Wildlife Do not allow the introduction of non-native amphibian species to the site. Ideally avoid amphibian re-introductions unless as part of well managed re- introduction programmes with rigorous biosecurity and infection screening protocols. Biosecurity People coming into contact with water or amphibians should ensure where possible that their equipment and footwear/clothing has been cleaned and fully dried before use if it has previously been used at another site. To properly clean footwear and equipment: First use a brush to clean off organic material e.

It causes a able severity generic 500mg glycomet amex, but is more likely to cause fulminant self-limiting acute hepatitis discount 500mg glycomet otc, with no chronic or carrier hepatic failure. Liver cell membranes may become immunogenic resulting in a lymphocyte-mediated cytotoxic response against Other liver diseases the liver cells. Alcohol-induced liver disease Clinical features Definition Differing patterns are seen: r Acute alcoholic hepatitis resembles acute viral hepati- Liver disease caused by alcohol range from a fatty liver to hepatitis and cirrhosis. Microscopy Aetiology There are three main patterns of liver damage: The risk of developing chronic disease is related to quan- r Alcoholic hepatitis is focal necrosis of hepatocytes, tity, types of beverage, drinking pattern (see page 521), with neutrophil infiltration. Characteristically Mallory’s bodies composed of cytoskeletal fragments Pathophysiology andubiquitin,aheatshockproteinthatlabelsproteins r Any alcohol ingestion causes changes in liver cells, as being damaged and targets them for breakdown. Alcoholic It appears as bright eosinophilic amorphous globules hepatitis refers to alcohol-induced liver injury visible within hepatocytes. This form of change is seen in those ingesting more than 80 g alcohol per day (6 units, 1 bottle of wine or 3 pints of beer). Steatosis r Cirrhosis: Repeated damage has led to fibrosis, with damage to the normal architecture upon which func- Steatohepatitis tion is dependent. Up to 10% of patients with cirrhosis, secondary to Cirrhosis alcohol use, develop hepatocellular carcinoma. Ultra- sound may show significant cholestasis and be mistaken liver injury, occurring in patients with little or no his- for extra-hepatic obstructive jaundice. In late stages patients ranges from fat accumulation in hepatocytes (hepatic maybeconsideredforlivertransplantiftheyhaveproved steatosis) to hepatic steatosis with hepatic inflamma- abstinence. The pathogenesis of nonalcoholic fatty liver disease is r Fatty liver is reversible, with complete recovery. However, if they abstain from drinking 90% acid entering the liver, decreased free fatty acid leav- have a full recovery. Insulin resistance appears to be important in the acute episode of hepatitis have the poorest prognosis development of hepatic steatosis and steatohepatitis. Chapter 5: Disorders of the liver 207 Clinical features Drug-induced liver disease Most patients are asymptomatic, fatigue, malaise and Hepatic injury caused by drugs accounts for 2–5% of rightupper abdominal discomfort may occur in some hospital admissions for jaundice. Hepatomegaly is a frequent find- atotoxicity may be subdivided into predictable (dose- ing. Most cases are found on incidental abnormal liver dependent) and idiosyncratic, although more than one function tests. Patients who develop cirrhosis may be at increased risk for hepatocellular carcinoma. Ultrasound r Idiosyncratic hepatotoxins appear to cause a chronic scan may indicate fatty infiltration. Management The pathophysiology of drug hepatotoxicity may also be r Obesity, hyperlipidemia and diabetes should be man- divided into the liver pathology caused (see Table 5. Definition r In the few patients who progress to end stage, liver Achronic hepatitis of unknown aetiology characterised failure transplantation may be required; however, re- by circulatingautoantibodiesandinflammatorychanges currence in the transplanted liver has been reported. Intrinsic Idiosyncratic hepatotoxins hepatotoxins Predictable Idiosyncratic Dose-dependent Dose-independent Common Rare Direct Indirect Hypersensitivity Abnormal (‘autoimmune’) metabolism Figure 5. Patients may have an acute hepatitis or complica- drugs tions of cirrhosis such as portal hypertension (e. In pa- steroids, azathioprine, cytotoxic tients who develop end stage liver disease despite med- drugs, alternative medicine such as ical treatment liver transplantation may be considered Bush Tea Liver tumours Oral contraceptive steroids, although hepatitis may recur in the transplanted organ. The risk of hepatocellular carcinoma is low, in contrast to chronic Prevalence active hepatitis due to viral causes. No autoimmune mechanism has yet been proven, al- though high titres of autoantibodies are characteristic. Sex Patients may have features that overlap with primary >90% female biliary cirrhosis and primary sclerosing cholangitis. Au- toimmune chronic hepatitis is also commonly associ- Aetiology ated with other autoimmune disorders e. Antibodies to mitochondria are diabetes mellitus, thyroiditis and ulcerative colitis (more present; however, their exact role in pathogenesis often associated with primary sclerosing cholangitis). Chapter 5: Disorders of the liver 209 Environmental triggers suggested include enterobacte- ducts. Pathophysiology Management Chronic inflammation of the small intrahepatic bile Supportive treatment involves ursodeoxycholic acid ducts leads to cholestasis and destruction of bile ducts. Duct plementation, management of complications such as epithelium in the pancreas, salivary and lacrimal glands varices, hyperlipidaemia. Pa- Asymptomatic patients may have a normal life ex- tients may complain of fatigue and pruritus, followed pectancy. Any sign of liver disease atomegaly, high bilirubin, low albumin and cirrhosis may be present, such as clubbing, hepatomegaly, spider correlate with shortened survival (5–7 years in severe naevi, xanthomata. Definition Macroscopy/microscopy A disease of unknown aetiology in which chronic in- Throughout the disease, copper accumulates due to the flammation of the bile ducts leads to stricture formation chronic cholestasis. There is also a strong association with inflam- Complications matory bowel disease, which is present in 60–75%, but r Oesophagealvarices,osteoporosis,osteomalacia,pan- may be asymptomatic. Chronic inflammation of the intra- and extra-hepatic r Associated with many other disorders, such as bile ducts leads to fibrosis and short strictures form Sjogren’s,¨ hypothyroidism, systemic lupus erythe- which obstruct the passage of bile.

Histology is a study of cell and tissue structures generic 500mg glycomet otc, performed by examination under a microscope generic glycomet 500 mg with amex. Histology is the study of healthy tissue and pathology includes the study of unhealthy tissue. The term “pathohistological” refers to studying characteristics of tumourous tissue under the microscope. A hot spot mutation is any locus in the deoxyribonucleic acid sequence or on a chromosome where mutations or aberrations occur preferentially. The Human Genome Project is an international scientifc research project with a primary goal of determining the genetic makeup of the human species. A working draft of the genome was announced in 2000 and a complete one in 2003, with further, more detailed analysis still being published. Most of the government-sponsored sequencing was performed in universities and research centres from the United States, the United Kingdom, Japan, France, Germany and Spain. Researchers continue to identify protein-coding genes and their functions; the objective is to fnd disease-causing genes and possibly use the information to develop more specifc treatments. The genome of any given individual (except for identical twins and cloned organisms) is unique; mapping the human genome involves sequencing multiple variations of each gene. Mutations may or may not produce discernible changes in the observable characteristics (phenotype) of an organism. Mutations play a part in both normal and abnormal biological processes, including evolution, cancer and the development of the immune system. Mutations in genes can either have no effect, alter the product of a gene, or prevent the gene from functioning properly or completely. Neoplasm is an abnormal mass of tissue as a result of the abnormal growth or division of cells. Prior to neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. The growth of neoplastic cells exceeds, and is not co-ordinated with, that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the stimuli. Proteomic changes represent changes in the expression, localisation, function, and interactions of proteins expressed by genetic material. Mutations that are not germline are somatic mutations, which are also called acquired mutations. Squamous tumour originates from a type of epithelial cell called the squamous cell. These cells form the main component of the superfcial part of the skin, and squamous cell carcinoma is one of the major forms of skin cancer. However, squamous cells also occur in the lining of the digestive tract, lungs and other areas of the body, and therefore squamous cell carcinoma occurs as a form of cancer in diverse tissues, including the lips, mouth, oesophagus, urinary bladder, prostate, lung, vagina and cervix among others. Despite sharing the name squamous cell carcinoma, the cancers of different body sites can show tremendous differences in their presenting symptoms, natural history, prognosis and response to treatment. The Forum brought together infuential leaders from the European cancer advocacy community to address different issues in personalised medicine. Confict of interest disclosure: Dr Marina Garassino – No conficts of interest to declare. Adolescence is a time when many young people express their autonomy by taking risks. Risk‐taking is a normal and positive development on the path to adulthood, but it also carries potential danger. One of the most common, and most dangerous, of adolescents’ risky behaviors is using illicit drugs. Illicit drugs include marijuana/hashish, cocaine (including crack), heroin, hallucinogens, inhalants, or psychotherapeutic 2 medications not taken under a health provider’s supervision. This Adolescent Health Highlight presents statistical information about the extent, types, and patterns of adolescents’ use of illicit drugs; discusses their effects on adolescents’ health and well‐being; shares findings from research about factors that can help adolescents avoid substance use and abuse; and presents strategies for preventing illicit drug use among adolescents and treating those with drug problems. Types and patterns of illicit drug use Marijuana (and hashish, a product derived from marijuana, and included here in all discussions of marijuana use) is by far the most commonly used illicit drug among adolescents. However, adolescents use a wide range of illicit drugs—some newly developed, some “rediscovered. Thus, it can be challenging to stay on top of all the varieties of illicit drugs adolescents are currently Unfortunately, word using. Moreover, some adolescents use multiple illicit drugs, either concurrently or over the 1 about “new” course of their adolescent years.

Human papillomavirus (viral warts) Incidence Affects 10–20% of the population at some time in their Definition lives discount 500 mg glycomet fast delivery. Like other herpes virus infections discount glycomet 500mg visa, it are high-risk subtypes for neoplasia and are associated then remains as a latent infection in the sensory dorsal with cervical and oral cancer. Clinical features 1 Common warts are well-demarcated dome shaped Clinical features papules or nodules with an irregular papilliferous sur- Pain,tendernessorparaesthesiadevelopsinthedistribu- face. Commonly occur on the back of hands, between tion of a single dermatome 3–5 days prior to the onset of fingers and around the nail edge. No treatment is universally successful, and as there is a Patients present with an inflamed glans and prepuce. Management Topical antifungals are used in the form of creams, Prognosis lozenges or pessaries. Fungal skin infections Dermatophyte (ring worm) fungi Candida albicans Definition Definition Dermatophytes or ringworm fungi invade keratin and Candida albicans,acommensal yeast of the gastroin- cause skin and nail infections. Aetiology/pathophysiology Lesions are single or multiple erythematous, scaly, Candida is a dimorphic fungus occurring as a yeast on well-demarcated patches on the scalp that gradually mucosal surfaces. Hairs within the patch break off giving a patch infections result from disruption of the normal body of alopecia. It is a form of immune response tend towards more extensive persistent mucous mem- to the fungus. Neutropenic patients are at risk of itraconazole or griseofulvin are effective even in ke- widespread disseminated illness. Patients develop itchy or painful, erythematous scaling lesions between the Clinical features toes. It may be acute self-limiting or a persistent 1 Oral candidiasis is commonly seen in babies and chronic infection. Topical antifungal agents are usu- patients treated with antibiotics or chemotherapy. Chapter 9: Infections of the skin and soft tissue 403 r Tinea Unguium: Nail infection with ringworm is Management common especially in the elderly. Patients develop Topical shampoo containing insecticides such as mala- asymmetrical discoloured (white/yellowish black) thion and permethrin may be used, although there thickened nails with crumbling white material un- is some evidence of increasing resistance. Mechanical removal of prolonged course of systemic antifungals as for tinea lice nit combs from wet hair is an alternative strategy. Household members should be examined and treated if r Tinea Cruris: Tinea cruris affects the groin with ery- infested. Severe or refractory cases require oral antifungals as for tinea Definition capitis. Parasitic skin infections Aetiology/pathophysiology Transmission of the mite occurs by skin–skin contact Head lice with an infested individual or contaminated clothing or bedding. The mite burrows down into the stratum Definition corneumofthe skin and then the female lays eggs. Clinical features Incidence r There is often a widespread, erythematous urticating Common rash all over the body as a result of a hypersensitiv- ity reaction to the mite. Age r On examination small papules and linear tracks, Occurs mainly in school children. Pediculosiscapitis orheadlouseisagrey-whiteinsectthat grasps on to hair and sucks blood. Insects are spread by contact The burrows and distribution pattern is very suggestive but as insects can survive for hours away from the host, of the diagnosis. The mite can be visualised using a der- transfer on clothing, shared combs, towels and beds may matoscope. Management Clinical features Patients are extremely infectious and require barrier Infestations are often asymptomatic although allergy nursing. The entire skin except the face should be treated may result in itching and lymphadenopathy. All close contacts re- louse is difficult to find but eggs (nits) may be seen along quire treatment, and clothing and bed linen should be the hair shaft. They are most common in Seborrhoeic keratoses patients who burn easily and tan poorly. There is debate Definition as to whether solar keratoses leads to squamous cell car- Seborrhoeic keratoses are a benign localised prolifera- cinoma, or whether squamous cell carcinomas arise in tion of the basal layer of the epidermis. Clinical features Lesions initially appear as a small, well-demarcated, red Incidence brown plaque that progress to become more erythema- Common; by age 40 approximately 10% of individuals tousandhyperkeratotic. Sex M = F Dermatofibromas Aetiology/pathophysiology Definition The cause of seborrhoeic keratoses is unclear, although Adermatofibroma is a cutaneous nodule containing they occur more commonly on sun-exposed skin. Sex 4F:1M Management If treatment is required, cryotherapy or currettage are Aetiology/pathophysiology usually effective. Historically dermatofibromas have been associated with trauma or insect bites, although the cause is unknown. Solar keratoses Definition Clinical features Solar keratoses or actinic keratoses are single, small scaly Lesions occur most commonly on the lower limbs.