Grant E. Lattin Jr., MD

• Assistant Professor of Radiology
• Uniformed Services University of the Health Sciences
• Bethesda, Maryland

Chronic meningococcal septicaemia spasms calf generic 200mg urispas free shipping, although uncommon muscle relaxant creams over the counter buy discount urispas, is characterized by intermittent pyrexia muscle relaxant with alcohol urispas 200mg without prescription, rash muscle relaxant back pain generic urispas 200mg without a prescription, and arthralgia spasms prostate 200 mg urispas overnight delivery. Occasionally a diagnosis is made retrospectively because of transient positive blood cultures in children with mild muscle relaxer kidney pain buy discount urispas 200mg on-line, self-limiting, febrile illness. To prevent secondary cases of meningococcal disease, household and secretion (kissing) contacts are offered antibiotic prophylaxis. The standard agent for prophylaxis is oral rifampicin, twice daily for 2 days (adults 600 mg; children 10 mg/kg). A single intramuscular injection of ceftriaxone (adults 250 mg; children 125 mg) or a single oral dose of ciprofloxacin (adults 500 mg) is an alternative prophylactic regimen. Patients who have had a splenectomy are at particular risk of developing overwhelming pneumococcal infection. The onset of pneumococcal meningitis may be sudden, and the course rapid with death occurring within 12 hours. Alterations of consciousness and focal neurological defects may occur and survivors often suffer significant neurological deficits. The global spread of penicillin-resistant pneumococci has eroded the efficacy of benzylpenicillin, which was formerly the drug of choice. Strains of pneumococci that are resistant to expanded-spectrum cephalosporins such as ceftriaxone are being increasingly reported from around the world but are currently rare in the United Kingdom; rifampicin and/or vancomycin have been used in such cases. Cefotaxime or ceftriaxone, both of which are active against -lactamase-producing and non-lactamaseproducing strains of H. Rifampicin is used as prophylaxis for all household contacts when there is an unvaccinated sibling in the house aged 4 years or younger. Culture-negative pyogenic meningitis About 40 per cent of patients presenting with meningitis will already have received antimicrobial therapy before lumbar puncture and this may lead to a change in the clinical presentation and failure to isolate an organism. Death or severe neurological disability is strongly associated with treatment delay, yet there is no single laboratory test that will reliably make or exclude the diagnosis. In many cases treatment must be started and continued on the basis of compatible clinical features. Clinical or radiological evidence of extra-neural tuberculosis may allow further diagnostic specimens. Treat tuberculous meningitis with four antituberculosis drugs and adjunctive dexamethasone: rifampicin, isoniazid, and pyrazinamide (see Chapter 30). The fourth drug-usually ethambutol-covers the possibility of isoniazid-resistant bacteria (around 5% in the United Kingdom); it adds little to the intracerebral activity of the other drugs in drug-susceptible disease. Patients often get worse before they get better, commonly due to hydrocephalus, cerebral infarction, expanding tuberculoma, and hyponatraemia. Neonatal meningitis the highest risk of developing meningitis in the newborn is within the first 2 months of life, the incidence being about 0. Predisposing factors include prematurity, low birth weight, prolonged and difficult labour, prolonged rupture of membranes, and maternal perinatal infection. Neonatal meningitis is usually the result of vertical transfer of pathogens from the mother in utero or during delivery, leading to early-onset (occurring within seven days of delivery) septicaemia or meningitis; less commonly, they are acquired from the environment, leading to late-onset meningitis (occurring after seven days and occasionally up to two months after delivery). The early signs and symptoms are often non-specific and include fever, lethargy, and refusal of feed. A bulging fontanelle, resulting from raised intracranial pressure, is a relatively late sign. A wide variety of organisms may be involved and their susceptibility to antibiotics can be unpredictable. Group B haemolytic streptococci the treatment of choice is high-dose benzylpenicillin for at least 2 weeks. There may be enhanced bacterial killing when benzylpenicillin is combined with gentamicin, and many centres give this combination for the first 7­10 days. Escherichia coli and other enterobacteraciae the most widely used antibiotic is high-dose cefotaxime, often in combination with gentamicin. Ceftazidime plus gentamicin, or a carbapenem, is used to treat Pseudomonas aeruginosa infections. The duration of therapy should be 3 weeks, since cerebritis may accompany the meningitis and requires more prolonged treatment. A summary of current recommendations for the initial therapy of the commoner forms of bacterial meningitis is outlined in Table 28. Unfortunately, 15­25 per cent of these patients develop meningitis at some point in the life of the shunt. Among many other microorganisms associated with such infections are Propionibacterium acnes, diphtheroids, enterococci, and Gram-negative bacilli. Blood cultures are positive only if meningitis is associated with a ventriculo-atrial shunt. Therapy should be commenced with parenteral vancomycin combined with oral rifampicin and daily intraventricular vancomycin. High-dose flucloxacillin should be substituted for parenteral vancomycin if the isolate proves sensitive. Age Cerebrospinal fluid Gram-film findings Gram-positive diplococcic Gram-positive bacilli Gram-negative bacilli No organisms seen Any age Gram-positive cocci in clusters Presumptive organism Treatment of choice Antibiotic(s) Str. Add vancomycin and/or rifampicin if reduced susceptibility to ceftriaxone suspected or known. Occasionally, it causes meningitis in immune-competent individuals; usually with a more virulent subspecies (C. Management revolves around killing the yeast, relieving any raised intracranial pressure and hydrocephalus, and addressing, if possible, the underlying immune suppression as follow: Kill the yeast with amphotericin B (the liposomal formulation is less nephrotoxic) and flucytosine (which enhances killing). If the patient remains severely immunosuppressed, lifelong low-dose fluconazole may be required. Consider a lumbar drain or ventriculo-peritoneal shunt if the patient deteriorates despite these measures. A rash (erythema migrans) can occur at the site of inoculation, and the bacteria may disseminate to the central nervous system. A later (but very rare) complication is chronic progressive encephalomyelitis, which mimics multiple sclerosis. International guidelines now recommend positive screening tests must be confirmed by western blot. If the cause of meningitis remains elusive, revisit the history, re-examine the patient, and repeat the lumbar puncture; and consider rare causes of meningitis, or conditions with similar symptoms and signs. Measles virus and Mycoplasma pneumoniae are the commonest causes of post-infectious encephalitis. Its clinical features range from mild slowing of mentation and impairment of attention, to coma. Focal neurological signs, especially when lateralized, or seizures strongly suggest encephalitis. Neurological findings in septic encephalopathy are usually symmetrical, such as paratonic rigidity; asterixis, tremor, or myoclonus are uncommon. They can infect the brain parenchyma (cerebral abscess) or occur between the dura and arachnoid mater (subdural empyema) through penetrating traumatic injuries, neurosurgery, haematogenous seeding. Collections of pus cause swinging fevers; when involving the brain, they also cause headache and, depending on location, focal neurological deficits and seizures. Determining the cause of the infection is important; however, take pretreatment blood cultures and submit pus for staining and culture (including for Mycob. Community-acquired brain abscesses should be treated with a third generation cephalosporin and metronidazole. Key points Viral meningitis is common and requires no treatment; bacterial meningitis is a life-threatening disease and requires rapid diagnosis and treatment. Abscesses of the brain vary by site; their microbiology is often mixed and reflects the predisposing condition. Their management requires coordination of radiological, neurosurgical and antibiotic expertise. Chapter 29 Skin and soft-tissue infections General considerations At birth the skin of the baby rapidly becomes colonized with bacteria from the mother, other handlers, and the environment. Some of these essentially non-pathogenic microbes, including coryneforms, coagulase-negative staphylococci, micrococci, and propionibacteria, become established as the resident flora of the normal skin. In intact skin these microorganisms usually prevent potential pathogens such as Staphylococcus aureus and Streptococcus pyogenes (haemolytic streptococci of Lancefield group A) from becoming established. However, if the skin is broken by accidental or surgical trauma, burns, a foreign body, or a primary skin disease (psoriasis, atopic dermatitis), these pathogens may not only become established as resident organisms-they may also give rise to infection of the skin and subcutaneous tissue. Many different microorganisms, including bacteria, fungi, and some viruses, may be involved in skin and soft-tissue infections. Thrush is usually caused by the yeast Candida albicans, and cold sores by the virus herpes simplex. Common clinical presentations Impetigo Impetigo consists of discrete purulent lesions on the exposed areas of the body, especially the face and extremities. Impetigo is most common in tropical countries but is also prevalent in more temperate zones, especially during the summer. The prevalence is strongly related to personal hygiene, and impetigo is much commoner in socially deprived communities. The lesions of impetigo start with papules that evolve into pustules and then form a characteristic thick crust over 4­7 days. Clinical diagnosis Most likely causes Impetigo Streptococcus pyogenes Staphylococcus aureus Antibacterial treatment Topical: fusidic acid or mupirocin; reserve for patients with a limited number of lesions Systemic: antistaphylococcal penicillin. Cellulitis, which is much more common, occurs in the deeper layers of the skin and subcutaneous tissues. The obviously affected area is red and hot but the demarcation between this and the normal skin is gradual and there is no palpable raised margin. It is more common if there is obstruction to venous or lymphatic drainage or gross obesity, which make the skin more fragile and local host defences less effective. In contrast, erysipelas occurs in the superficial layers of the skin and results in a very clear, abrupt line of demarcation between the affected and normal skin, with a palpable lesion that is raised above the level of the normal skin. Erysipelas usually occurs on the face or on the legs, whereas cellulitis can occur anywhere on the body, although it is commonest on the legs. Systemic inflammatory response means that the patient has sepsis and is at risk of progressing to severe sepsis or septic shock (see Chapter 26). Blood cultures should be taken from patients with sepsis arising from cellulitis, as about 50 per cent are positive. In theory, erysipelas could be treated with penicillin V but it is not worth taking the risk that the cause may be Staph. There is a belief that an antistaphylococcal penicillin should be combined with benzylpenicillin or penicillin V, since the latter are much more active against Str. However, provided antistaphylococcal penicillins are given in adequate dosage, they are just as effective alone. Prevention of recurrent cellulitis requires enhancement of host defences by preventing breaks in the skin. If these measures fail, then long-term prophylactic antibiotics are unfortunately not usually effective. It is preferable to give the patient a course of antibiotics to start as soon as symptoms begin. Cellulitis following animal or human bites Infections following animal bites are polymicrobial, often including anaerobic bacteria and unusual organisms such as Pasteurella multocida, a human pathogen that is part of the normal oral flora of cats. Human bites are often associated with greater damage to the skin and soft tissues and are also polymicrobial, with aerobic and anaerobic bacteria. Diabetic foot infections Infections of the feet are particularly common in diabetics because several important host defences, including circulation and sensation, are compromised. This enables minor injuries to progress to advanced stages of infection rapidly and with very few symptoms. Consequently it is vital to educate patients with diabetes about how to avoid trauma to the feet and how to recognize infection early. Chronic ulcers without spreading cellulitis do not require antibiotic treatment, even if there is some purulence in the exudate, as this simply indicates bacterial colonization of the ulcer. If there is cellulitis spreading up to 2 cm from the margin of the ulcer, the infection is likely to respond to oral antibiotics but, if the infection spreads more widely or is associated with signs of sepsis, then referral to hospital for intravenous treatment should be considered. Taking swabs from chronic ulcers is not helpful because they will be colonized with possibly harmless bacteria; even if infection is present, the bacteria cultured are not always the ones that are responsible. Meaningful cultures can be obtained only by debriding the ulcer and then obtaining tissue specimens from the base of the lesion by curettage (scrapings with a sterile blade). Because of the combination of impaired circulation and sensation, diabetic foot infections are particularly likely to progress to osteomyelitis because they may be present for weeks before the patient seeks medical attention. Osteomyelitis should be considered as a potential complication of any deep or extensive ulcer, especially if it is overlying a bony prominence or contains visible bone particles. Superficial fungal infections usually respond to topical therapy (Chapter 22), although dermatophyte infections of finger- or toenails may require oral treatment with terbinafine for up to 3 months or with griseofulvin for a year or more. These agents are deposited in newly formed keratin, and the prolonged treatment is needed to allow healthy nail to replace the diseased tissue. Even so, treatment of chronic infections of toenails may be unsuccessful, although terbinafine is more reliable in this respect than griseofulvin. Severe skin and soft-tissue infections Necrotizing fasciitis and toxic shock syndrome have received considerable media attention. However both of these problems are rare in comparison with severe sepsis associated with cellulitis. In comparison with pneumonia, relatively little attention has been given to auditing and improving the management of severe skin and soft-tissue infection. This should include clindamycin both for cover against anaerobic bacteria and because clindamycin reduces toxin production by bacteria. However, studies of the management of skin and soft-tissue infection show that most antibiotic treatment is inappropriate, with under-treatment of severe infections as well as over-treatment of uncomplicated infections (Table 29. It is important to be aware that 20 per cent of patients with severe community-acquired cellulitis do not have signs of systemic inflammatory response on admission to hospital, so re-assessment within the first 24 hours of admission is essential.

Unfortunately muscle relaxant shot for back pain purchase discount urispas line, Gram-negative bacteria then became the major pathogens found in hospitals and rapidly acquired resistance to multiple antibiotics in the succeeding years spasms of the heart buy 200 mg urispas with visa. In the 1970s the pendulum swung the other way muscle relaxant potency best 200mg urispas, with the first outbreaks of hospital infection with multiresistant staphylococci that were resistant to nearly all antistaphylococcal agents xanax muscle relaxant dosage order cheap urispas line. Outbreaks of infection caused by such organisms have occurred subsequently all over the world spasms in 6 month old baby buy urispas 200mg fast delivery. Gram-negative bacteria are once again assuming greater importance spasms coronary artery purchase urispas australia, particularly in hospitals. Resistance to newer cephalosporins-mediated by extended-spectrum -lactamases-and fluoroquinolones in E. Some Gram-negative bacilli may produce both drug-inactivating enzymes and altered porins and thus become resistant to carbapenems because of a combination of antibiotic cleavage and reduced cell penetration. Types of acquired resistance Two main types of acquired resistance may be encountered in bacterial species that would normally be considered susceptible to a particular antibacterial agent: mutational resistance and transmissible resistance. Mutational resistance In any large population of bacterial cells, a very few individual cells may spontaneously become resistant (see Chapter 11). Such resistant cells have no particular survival advantage in the absence of antibiotic but, after the introduction of antibiotic treatment, susceptible bacterial cells will be killed, so that the (initially) very few resistant cells can proliferate until they eventually form a wholly resistant population. Many antimicrobial agents select for this type of acquired resistance in many different bacterial species, both in vitro and in vivo. Transmissible resistance A more spectacular type of acquired resistance occurs when genes conferring antibiotic resistance transfer from a resistant bacterial cell to a sensitive one. Exponential transfer and spread of existing resistance genes through a previously susceptible bacterial population is a much more efficient mechanism of acquiring resistance than the development of resistance by mutation of individual susceptible cells. Notably, however resistance appears in a hitherto susceptible bacterial cell or population, it will only become widespread under the selective pressures produced by the presence of appropriate antibiotics. In addition, the development of resistant cells does not have to happen often or on a large scale. A single mutation or transfer event can, if the appropriate selective pressures are operating, lead to the replacement of a susceptible population by a resistant one. Without selective pressure, antibiotic resistance may be a handicap rather than an asset to a bacterium. Cross-resistance involves resistance to a number of different members of a group of (usually) chemically related agents that are affected alike by the same resistance mechanism. Thus, resistance to aminoglycosides may be mediated by any one of a number of different drug-inactivating enzymes (see Table 11. For example, a change in the outer membrane structure of Gram-negative bacilli may concomitantly deny access of unrelated compounds to their target sites. In contrast, multiple drug (multidrug) resistance involves a bacterium becoming resistant to several unrelated antibiotics by different resistance mechanisms. For example, if a staphylococcus is resistant to penicillin, gentamicin, and tetracycline, the resistances must have originated independently, since the strain destroys the penicillin with a -lactamase, inactivates gentamicin with an aminoglycosidemodifying enzyme, and excludes tetracycline from the cell by an active efflux mechanism. It is, however, not always clear whether cross-resistance or multiple resistance is being observed. Genes conferring resistance to several unrelated agents can be transferred en bloc from one bacterial cell to another on plasmids (see Chapter 11), thereby giving the appearance of cross-resistance. In such cases, detailed biochemical and genetic analysis may be required to prove that the resistance mechanisms are distinct (multiple resistance), although the genes conferring resistance are linked and transferred together on one plasmid. The clinical problem of drug resistance Concerns about resistance have been raised at regular intervals since the first introduction of antimicrobial chemotherapy but awareness of the antibiotic resistance problem has probably never been greater than it is today. For example, a 2013 report estimated that in the United States alone at least two million people acquire serious infections with bacteria that are resistant to one or more antibiotics of potential use in such cases. It is important not to understate or overstate the problem; the situation is presently becoming serious but is not yet desperate, since most infections are still treatable with several currently available agents. This may, however, mean that the only antibiotics that are still active are more toxic or less effective (or both) than those to which bacteria have acquired resistance. For example, it is generally accepted that glycopeptide antibiotics are less effective in the treatment of Staph. This means that clinicians are likely to opt for unnecessarily broad-spectrum therapy, particularly in critically ill patients. Unfortunately, repeated use of such regimens against bacteria that harbour resistance genes intensifies the selective pressure for further resistance development, notably in hospitals, where the most vulnerable patients are managed. In many less-developed countries of the world, the therapeutic options may be severely restricted for economic reasons. There is no doubt that the problem of antibiotic resistance is a global issue, and in future years there is a real possibility that physicians will be faced increasingly with infections for which effective treatment is not available. There are many examples of the intercontinental spread of resistant pathogens, and so the judicious use of antibiotics has global as well as local relevance. Although cephalosporins, quinolones, and aminoglycosides have been developed to cope with the problem, resistance to these newer compounds has increased in most countries. Outbreaks of infection caused by multiresistant Klebsiella strains and extended-spectrum -lactamase-producing enterobacteria in general are reported increasingly often, both in high dependency areas of hospitals and in urinary tract isolates from patients in the community. The latter phenomenon is consistent with more widespread dissemination of these strains and their carriage in faecal flora. There is evidence that such strains have spread between countries, particularly in patients undergoing hospital treatment in multiple settings. Widespread resistance in enteric bacteria is a particular problem in less-developed areas, where heavy and indiscriminate use of antibiotics may combine with a high prevalence of drug-resistant bacteria in the faecal flora or even in the environment, poor standards of sanitation, and a high incidence of diarrhoeal disease to encourage the rapid emergence and spread of multiresistant strains of enteric bacteria. Epidemics of diarrhoeal disease caused by multiresistant strains of intestinal pathogens, including Vibrio cholerae, shigellae, salmonellae, and toxin-producing strains of E. Acinetobacter these organisms cause hospital-acquired infections, especially in patients in intensive care units, for example, in patients with ventilator-associated pneumonia. Such infections are usually extremely difficult to treat because of the multiple classes of antibiotic resistance found in these bacteria. Very few antibiotics are now reliably effective for the treatment of acinetobacter infections. Colistin, a relatively toxic old antibiotic that has largely been abandoned for systemic administration, is used to treat some strains that are resistant to all other licensed antibiotics. More recent antibiotics, including linezolid, daptomycin, and tigecycline, are active against these strains but resistance to these also occasionally occurs. Coagulase-negative staphylococci and enterococci are often multiresistant and cause infections typically in patients with indwelling prosthetic material, such as catheters, vascular grafts, joints, and heart valves. A combination of antibiotics may be required to treat serious enterococcal infections but the emergence of high-level aminoglycoside resistance may seriously limit this option. Enterococci carrying genes conferring high-level resistance to glycopeptides have emerged (Chapter 10). Linezolid has been used successfully to treat infection caused by such strains, but resistance has some occurred in patients receiving long courses of therapy, particularly if the focus of infection has not been removed. Unfortunately, isolates with resistance to most antibiotics can now be found in most countries of the world. The prevalence of macrolide-resistant pneumococci tends to correlate with how often these antibiotics are used, especially in the community, where most respiratory tract infections are treated. Some resistance emergence has developed in units where these agents have been used commonly. Decreased levels of susceptibility of Neisseria meningitidis to penicillin have been seen in many countries but high-level resistance is exceptionally rare. Currently, penicillin is still used empirically in some cases of suspected meningococcal infection. Ironically, treating all gonococcal infections with one particular (presumed) active antibiotic may actually hasten the emergence of resistance, via selective pressure, to that agent. The resistant bacteria can be transmitted, for example, in hospitals, in prisons, and in the community and represent a major public health issue. The emergence of resistance is associated with poor compliance with antituberculosis medication. Directly observed therapy is advocated therefore for patients in whom compliance may be unreliable (see Chapter 30). Key points the extent of antibiotic resistance does not reverse in some cases when antibiotics stop being used. There is no clear explanation for the marked differences in rate or extent of acquisition of resistance between different bacterial species. Widespread resistance has emerged to each of the successive antibiotics used to treated gonorrhoea. Department of Health, Public Health England and Department for Environment, Food, and Rural Affairs. However, attempts to limit the spread of drug resistance require not only knowledge of the mechanisms themselves, but also an understanding of the genetic factors that control their emergence and continued evolution. Genetics of resistance All the properties of a microbial cell, including its antibiotic resistance and virulence determinants, are determined ultimately by the microbial genome. The genome comprises the three possible sources of genetic information: the chromosome, plasmids, and bacteriophages. An example of a bacterial species with a high degree of intrinsic resistance is Pseudomonas aeruginosa. By contrast, acquired resistance occurs in formerly susceptible cells, either following alterations to the existing genome or by transfer of genetic information between cells. Thus, a basic knowledge of microbial genetics is essential to understand the development and spread of resistance to antimicrobial drugs. The chromosome is found in the cytoplasm of the cell, not separated from it by a nuclear membrane. Not all of these genes need to be expressed at any one time, and indeed it would be wasteful for the cell to do so. Gene regulation is therefore necessary and can occur at either the transcriptional or translational level. They usually involve deletion, substitution, or addition of one or only a few base pairs and thus alter the amino acid composition of a specific protein. They occur continuously in cell genes and are independent of the presence or absence of antibiotics. In the presence of an antibiotic, some of these occasional spontaneous antibiotic-resistant mutants that are present among a predominantly susceptible population of bacteria may be selected. In such a situation, the susceptible cells will be killed or inhibited by the antibiotic, whereas the resistant mutants will survive and proliferate to become the new predominant type. Most chromosomal resistance mutations result in alterations to permeability or specific antibiotic target sites but some result in the enhanced production of an inactivating enzyme or bypass mechanism. The latter types are mutations at the transcriptional or translational level in gene regulatory mechanisms. Chromosomal mutations causing antibiotic resistance can be divided into single-step and multistep types. Single large-step mutations With these mutations, a single mutational change results in a large increase in the minimum inhibitory concentration of a particular antibiotic and may lead to treatment failure if this drug is used alone. Multistep (stepwise) mutations these are sequential mutations that result in cumulative gradual stepwise increases in the minimum inhibitory concentration of a particular antibiotic. They are clinically quite common, especially in situations where only low concentrations of antibiotic can be delivered to the site of an infection. Plasmids can carry genes that confer a wide range of properties on the host cell and, while such properties are usually not essential for survival, they offer a survival advantage in unusual or adverse conditions. There are at least 20 incompatibility groups within the plasmids found in enteric Gram-negative bacilli, and similar incompatibility schemes are used to subdivide staphylococcal plasmids and those found in Pseudomonas spp. Bacteriophages the third possible source of genetic information in a bacterial cell is a bacteriophage. Most phages will attack only a relatively limited range of bacteria, and can be divided into two main types: virulent phages, which inevitably destroy by lysis any bacteria that they infect, with the consequent release of numerous new phage particles from the lysed cell; and temperate (lysogenic) phages, which may either lyse or lysogenize infected bacterial cells. For the latter class of phages, during the lysogenic cycle, the phage nucleic acid is replicated in a stable and dormant fashion within the infected cell, often following insertion into the host cell chromosome. However, while in the prophage state, some prophage genes may be expressed and may confer additional properties on the cell. Once in every few thousand cell divisions, a prophage becomes released from the dormant state and enters the lytic cycle, with subsequent destruction of its host cell and release of new phage particles into the surrounding medium. Naturally occurring phages have been used in limited settings (for example, the countries formerly part of the Soviet Union) for the treatment of some infections (phage therapy). Some companies are exploring such treatment modalities in response to the threat posed by antibioticresistant pathogens. Transfer of genetic information There are three ways in which genetic information can be transferred from one bacterial cell into another: transformation, transduction, and conjugation. This process has been much studied in the laboratory but there are few convincing demonstrations of its occurrence in vivo. They can, therefore, acquire and express blocks of genetic information that have evolved elsewhere. A bacterial cell can, for example, acquire by conjugation a plasmid that carries genes conferring resistance to several different antibiotics. Of course, the ability to transfer genes in this way does not eliminate the need for these to evolve; however, once they have evolved, it ensures their eventual widespread dissemination under appropriate selection pressures. Evolution of new resistance gene combinations the distinction between chromosomal and plasmid genes is not absolute. Although this process can lead to the formation of new antibiotic resistance gene combinations, it is relatively uncommon in bacteria because there are few regions of sequence homology between the bacterial chromosome and plasmids that can be exploited for this purpose. Transposons h Transposition depends on the existence of specific genetic elements termed transposons.

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Treatment with any of these agents needs to be prolonged and is an adjunct to other measures aimed at improving the condition spasms hiatal hernia discount urispas 200mg online. Burns the treatment of burns is a very specialized topic that cannot be covered adequately in this chapter quinine muscle relaxant mechanism buy urispas overnight. However muscle relaxant gas generic urispas 200mg, topical agents do have definite value in the prevention of infection in patients with burns spasms pronunciation order 200mg urispas otc, so it is appropriate that their use should be mentioned muscle relaxant voltaren discount urispas 200 mg visa. Initially spasms in your stomach proven urispas 200 mg, a thermal burn renders the skin sterile but bacterial colonization is inevitable, even with scrupulous aseptic technique. Prophylaxis with topical antibiotics and antiseptics has been shown significantly to reduce colonization and sepsis. None of these agents will reliably prevent infection by multiresistant Gram-negative rods, especially Ps. Aggressive surgical approaches, including early wound closure by skin grafting after debridement, have reduced the requirement for topical applications to burned tissues. In cases in which infection becomes established, systemic drugs will often have to be employed, the choice being dictated by laboratory tests. However, since the penetration of antibiotics to surface lesions with a poor blood supply may be inadequate, topical dressings are additionally required. Urinary and respiratory infections are commonly encountered in the burned patient and may result in bacteraemia with sepsis, which has a poor prognosis. These infections require, of course, systemic therapy but choice may be limited by bacterial resistance, since many burns units are notorious for the prevalence of highly resistant strains, especially of Ps. Skin ulcers Ulceration of the skin of the leg or the area overlying the sacrum may arise from a variety of pathological states, and colonization is usually a sequela, not an initiating event. Disorders of the circulation, including obliterative arterial disease, small-vessel damage consequent on diabetes mellitus, and varicose veins, are the most common underlying conditions; correction of the underlying cause is essential to the healing of any ulcer. Continuous pressure is another common factor in the formation of a break in the skin, particularly in the bed ridden. This problem has led to the development of special air beds and cushions to minimize local vascular occlusion to the skin overlying bony areas such as the sacrum. The presence of colonization in a skin ulcer may be detected by odour and appearance of pus, which in the case of pseudomonas infection may be characteristically green. However, colonization is not an indication for antibacterial treatment, which should be reserved for patients with spreading cellulitis or systemic inflammatory response (Chapter 29). Swab reports showing the presence of potential pathogens do not prove infection since colonization of a large raw skin area is inevitable. Some chemical antiseptics are cytotoxic and impair wound healing; consequently, older remedies such as honey, sugar, and vinegar may be as effective as modern antiseptics. Many weeks of regular dressing combined with bed rest may be required to heal large ulcers; admission to hospital often speeds up the process. Skin grafting or vascular surgery (to improve the blood supply) can be considered for the most recalcitrant cases. Superficial fungal infections Confirmation of the diagnosis of superficial fungal infections such as ringworm and tinea pedis of the skin, or thrush of the mouth or vagina, depends on laboratory investigation of appropriate specimens from the affected area (nail, hair, skin scrapings, swabs of lesions of mucous membranes). Microscopy alone will be sufficient to establish a fungal cause in most cases but culture is necessary to identify the aetiological agent. Susceptibility testing presents technical difficulties but dermatophytes may usually be assumed to be susceptible to appropriate agents (see Table 4. For superficial skin infections, old-fashioned remedies, such as benzoic acid-containing ointments. Oral griseofulvin and terbinafine are suited to this purpose, since they are absorbed from the gastrointestinal tract and are preferentially concentrated in keratin. Topical treatment with amorolfine or tioconazole, which are formulated to penetrate nails, are less effective than terbinafine. If there is clinical evidence for invasive infection as, for example, Candida oesophagitis, appropriate systemic drugs, such as amphotericin, 5-fluorocytosine, fluconazole, ketoconazole, or itraconazole must be added. Although the direct toxic effects of drugs given systemically are reduced, exposed tissues and mucous membranes offer a fairly efficient site for drug absorption. For example, aminoglycoside ototoxicity has been reported following local application of neomycin, especially in the newborn. A more frequently observed effect is sensitization to the agent so that subsequent use of the drug, either topically or parenterally, produces a hypersensitivity reaction. Penicillin, in particular, is prone to sensitize the host and, because of possible anaphylactic reactions, it is not advisable to use any -lactam antibiotic on the skin. A further hazard of topical therapy is that local irritation may lead to a delay in wound healing, even though the actual infection is controlled. Superinfection with resistant bacteria or with fungi is a common consequence of using any topical antibiotic for a prolonged period. This is particularly likely to occur in burns units and dermatology wards, where there are many patients with large open skin lesions. Prevention of infection and cross-infection by aseptic methods is desirable, but often difficult in practice. In this manner, topical agents select multiresistant organisms, which may subsequently cause systemic infection in the patient or, by cross-infection, others. Tetracycline eye drops select for tetracycline-resistant bacteria in the mouth flora when used for mass population treatment of trachoma. The explanation is likely to be that medications administered to the eye can readily reach the nasopharynx via the naso-lachrymal duct. Selection of resistant bacteria is the most powerful argument against the indiscriminate use of topical antibiotics and, since antiseptics lack this disadvantage, they are to be preferred wherever possible. The major drawback to topical treatment of skin infections is that, even in the most superficial skin lesion, there may be areas inaccessible to a topical approach. Superinfection with fungi/resistant bacteria and selection of resistant strains during treatment are both common consequences of using any topical antibiotic for a prolonged period. Widespread use of one particular agent will lead to a larger reservoir of resistant organisms and the possibility of cross-infection. Chapter 23 Urinary tract infections Introduction to urinary tract infections Urinary tract infection is the second most common clinical indication for empirical antimicrobial treatment in primary and secondary care; respiratory tract infections are the commonest clinical indication in both settings. Urine samples constitute the largest single category of specimens examined in most medical microbiology laboratories. Health-care practitioners regularly have to make decisions about prescription of antibiotics for urinary tract infection. Criteria for the diagnosis of urinary tract infection vary depending on the patient and the context. Diagnostic methods Culture of bacteria from urine the laboratory confirmation of bacteriuria is made by quantitative culture of an uncontaminated urine specimen. The most reliable methods for obtaining a urine sample without contamination by skin or perineal flora are by suprapubic aspiration of the bladder with a syringe and needle or by urethral catheterization. Neither of these is practical or acceptable in clinical practice, so urine samples are collected during micturition. The practice of cleansing the perineum and taking the specimen in the middle of micturition minimizes the risk of contamination by the perineal flora. However, it is critical that cultures of urine are done as quickly as possible; otherwise, a few contaminating bacteria from skin and perineal flora will multiply in a few hours at room temperature and give false positive results. Alternatively, culture of urine as soon as it is passed can circumvent the possibility of contaminants growing in the urine during transit. This is achieved by using dip-inoculum methods, which consist of agar attached to slides or spoons that are dipped in the urine, drained, and transported in a stoppered bottle to the laboratory, where any bacterial colonies are counted after overnight incubation at 37°C. The symptoms of urinary tract infection can be associated with lower counts of bacteria: 103 organisms/ml in men and 102 organisms/ml in women. However, most clinical laboratories cannot detect such low levels of bacteria with routine methods, so in practice the threshold for significant bacteriuria remains at 105 organisms/ml. Urine dipstick testing Urine dipsticks use reagents to detect the presence of chemicals in the urine. The presence of leucocyte esterase is associated with the presence of white blood cells in the urine, which may in turn be associated with urinary tract infection. However, any cause of inflammation of the urinary tract will result in white cells in the urine. Other substances (blood or protein) can be present in the urine of patients with symptomatic urinary tract infection but they are even less specific to the diagnosis than nitrites or leucocyte esterase. Management of common clinical problems Asymptomatic bacteriuria Although normal urine is sterile some healthy people have bacteriuria without any symptoms. The prevalence at any given age is related to sexual activity: 5 per cent of married women aged 24­44 are likely to have asymptomatic bacteriuria, compared with <1 per cent of nuns of the same age. As with women, the prevalence of bacteriuria in men increases with age but it is always lower than in women of the same age. In the elderly the prevalence in men and women increases with deterioration of health and reaches 100 per cent in anybody who has an indwelling urinary catheter present for >4 weeks (Table 23. Category Healthy, ambulatory Institutionalized Indwelling urinary catheter for >4 weeks Men (%) 7 37 100 Women (%) 17 57 100 renal impairment. Young children who have had symptomatic urinary tract infection are therefore followed up after treatment to ensure that they do not have continuing bacteriuria. Moreover, there is good evidence that antibiotic treatment of asymptomatic bacteriuria reduces the risk of both these outcomes. Consequently, all pregnant women should be screened in the first trimester of pregnancy, and women with bacteriuria should be treated. Placebocontrolled trials have failed to show convincing benefit in patients with diabetes, in institutionalized elderly men or women, or in those with long-term indwelling catheters, whereas the same trials did show increased risk of adverse events in the treated patients, including colonization with antibiotic-resistant bacteria. The important point to remember is that bacteriuria is not diagnostic of urinary tract infection, which only occurs once bacteria invade the tissues of the urinary tract. Symptomatic urinary tract infection Lower urinary tract infection in non-pregnant women (uncomplicated urinary tract infection) Infection of the tissues of the bladder or urethra causes increased frequency of micturition with severe burning pain on passing urine (dysuria). The walls of the bladder and urethra have a relatively poor blood supply and so bacteria are not able to penetrate into the blood; people with lower urinary tract infection do not have a systemic inflammatory response. In fact, if a patient presents with dysuria, frequency, and symptoms of systemic inflammatory response, it should be assumed that they have upper urinary tract infection. The symptoms of lower urinary tract infection can be very severe and make it impossible for patients to continue their normal lives without effective treatment. Cystitis means inflammation of the bladder and is sometimes used as a pseudonym for lower urinary tract infection, although strictly the term should be bacterial cystitis to distinguish from other causes of cystitis. Uncomplicated urinary tract infection is defined as lower urinary tract infection in nonpregnant women with no underlying anatomical abnormalities that predispose to recurrent urinary tract infection. This is why lower urinary tract infection in men is classified as complicated, because it is likely to be associated with prostatitis, in which case it is likely to relapse unless antibiotics are continued for 2 weeks. This is why all upper urinary tract infections and also symptoms of lower urinary tract infections in pregnant women are classed as complicated, because both problems are associated with immediate risk to the patient from sepsis or severe sepsis. Clinical diagnosis of lower urinary tract infection is reliable in young adult women who have dysuria and frequency but no history of vaginal discharge. Urinary tract infection is difficult to diagnose in older women because it is more likely to present with vague, generalized symptoms. Moreover the prevalence of asymptomatic bacteriuria increases steadily with age and with increasing co-morbidity. Over 50 per cent of institutionalized elderly women have asymptomatic bacteriuria all of the time. The decision to give antibiotic treatment should be based on clinical diagnosis of infection, supported by acute local or systemic symptoms of inflammation. Smelly urine just means that the patient has bacteriuria, which is not unusual and does not require antibiotic treatment. In domiciliary practice, Escherichia coli predominates, accounting for at least 80 per cent of isolates. However, in countries with lower antibiotic use, such as the Netherlands and the United Kingdom, resistance to trimethoprim remains at about 20 per cent; guidelines recommend empirical treatment without urine culture for women with obvious symptoms because trimethoprim is extremely well tolerated (Table 23. However, the risk of infection with trimethoprim-resistant bacteria is increased in women who have been exposed to co-trimoxazole or trimethoprim in the past three months, and these women should be treated with nitrofurantoin. The use of co-trimoxazole is not recommended in the treatment of urinary infection in the United Kingdom, since the sulphonamide component plays an insignificant role and trimethoprim alone is less toxic. For bacteria that are resistant to nitrofurantoin and trimethoprim, or for patients who cannot tolerate these drugs, there is a range of alternative oral agents, including co-amoxiclav, ciprofloxacin, and pivmecillinam. The reason that these drugs are not used first line is that they are no more effective than nitrofurantoin or trimethoprim and have more adverse effects (Table 23. They should be reserved for patients in whom these first line agents are ineffective or contraindicated. Note that efficacy rates may vary geographically depending on local patterns of antimicrobial resistance among uropathogens. Fosfomycin is an antibiotic that was discovered over 35 years ago but until recently was only used in a few European countries. An oral formulation is available, and fosfomycin may provide the only option for oral treatment of some urinary tract infections in primary care. Recurrent symptomatic infections in women Recurrent urinary tract infection in healthy non-pregnant women is defined as three or more episodes during a 12-month period. A single dose of either trimethoprim or nitrofurantoin taken at night reduces the risk of symptomatic infection to about one-fifth of the risk with no treatment. However, the risk of recurrent urinary infection may return to pretreatment levels as soon as treatment is stopped. An alternative, equally effective strategy for women with infection associated with sexual intercourse is to take a single post-coital dose of antibiotic. Prophylactic antibiotics for recurrent infection have side effects (oral or vaginal candidiasis and gastrointestinal symptoms) but infection by bacteria resistant to the prophylactic antibiotic does not appear to be a significant risk.

The radiographic appearance is of a sharplycircumscribed muscle relaxant tv 4096 discount urispas on line, lytic lesion with multiple small foci of calcification spasms of the esophagus quality 200mg urispas. Histologically spasms lung order urispas with visa, the tumour is highly cellular and is composed of small muscle relaxant that starts with the letter z buy 200mg urispas with amex, round to polygonal mononuclear cells resembling chondroblasts and has multinucleate osteoclastlike giant cells infantile spasms 6 months old buy urispas toronto. The overlying cap shows mature cartilage cells covering the underlying mature lamellar bone containing marrow spaces spasms icd-9 urispas 200mg fast delivery. The lesion may be asymptomatic, or may cause pain, swelling and discomfort in the affected joint. Cut surface of the tumour is soft to firm and lobulated but calcification within the tumour is not as common as with other cartilageforming tumours. The lobules themselves are composed of immature cartilage consisting of spindleshaped or stellate cells with abundant myxoid or chondroid intercellular matrix. In view of close histogenetic relationship between chondro myxoid fibroma and chondroblastoma, occasional tumours show a combination of histological features of both. In frequency, it is next in frequency to osteosarcoma but is relatively slowgrowing and thus has a much better prognosis than that of osteosarcoma. It may be primary or secondary occurring on a preexisting benign cartilaginous tumour such as osteocartilaginous exostoses (osteochondromas), multiple enchondromatosis, and rarely, chondroblastoma. Both forms of chondrosarcoma usually occur in patients between 3rd and 6th decades of life with slight male preponderance. Clinically, the tumour is slowgrowing and comes to attention because of pain and gradual enlargement over the years. However, sometimes distinction between a welldifferentiated chondrosarcoma and a benign chon droma may be difficult and in such cases location, clinical features and radiological appearance are often helpful. Rare variants of chondrosarcoma are mesenchymal chondrosarcoma, dedifferentiated chondrosarcoma and clear cell chondrosarcoma. Clinical features at presentation include pain, especially on weightbearing and movement, noticeable swelling and pathological fracture. Giant cells often contain as many as 100 benign nuclei and have many similarities to normal osteoclasts. Stromal cells are mononuclear cells and are the real tumour cells and their histologic appearance determines the biologic behaviour of the tumour. Typically, they are uniform, plump, spindleshaped or round to oval cells with numerous mitotic figures. Other features of the stroma include its scanty collagen content, rich vascularity, areas of haemorrhages and presence of macrophages. These are: its cell of origin, its differentiation from other giant cell lesions and its biologic behaviour. Microscopy reveals osteoclastlike multinucleate giant cells which are regularly distributed among the mononuclear stromal cells. About 40 to 60% of them recur after curettage, sometimes after a few decades of initial resection. Metastases are histologically benign and there is usually history of repeated curettages and recurrences. Thus attempts at histologic grading of giant cell tumour do not always yield satisfactory results. One of the factors considered significant in malignant transformation of this tumour is the role of radiotherapy resulting in development of postradiation bone sarcoma. The three are linked together by a common neuroecto dermal origin and by a common cytogenetic translocation abnormality t(11; 22) (q24; q12). The common sites are shafts and metaphysis of long bones, particularly femur, tibia, humerus and fibula, although some flat bones such as pelvis and scapula may also be involved. Pattern the tumour is divided by fibrous septa into irregular lobules of closelypacked tumour cells. These tumour cells are characteristically arranged around capillaries forming pseudorosettes. Chordomas thus occur in the axial skeleton, particularly sacrum and coccyx (50%), sphenooccipital region (35%), and less often in the spine (15%). Recurrences after local excision are frequent and the tumour almost invariably proves fatal. Chondrosarcoma occurs in 4th to 6th decade, is seen more often in central skeleton and is a slow growing malignant tumour. Giant cell tumour is an aggressive and recurrent tumour arising in epiphysis, often occurring in young adults. Metastatic bone tumours are more common and may arise from various carcinomas and some sarcomas. The synovial membrane is composed of inner layer of 14 cell thick synoviocytes and outer layer of loose vascular connective tissue. Type A synoviocytes are more numerous and are related to macrophages and produce degradative enzymes, while type B synthesise hyaluronic acid. Articular cartilages the regressive changes are most marked in the weightbearing regions of articular cartilages. Initially, there is loss of cartilaginous matrix (proteoglycans) resulting in progressive loss of normal metachromasia. Initially, there are no pathologic changes in the synovium but in advanced cases there is lowgrade chronic synovitis and villous hypertrophy. The onset of disease is insidious, beginning with prodrome of fatigue, weakness, joint stiffness, vague arthralgias and myalgias. Approximately 20% of patients develop rheumatoid nodules located over the extensor surfaces of the elbows and fingers. Histologically, the characteristic feature is diffuse proliferative synovitis with formation of pannus. Intense inflammatory cell infiltrate in the synovial membrane with predominance of lymphocytes, plasma cells and some macrophages, at places forming lymphoid follicles. This invasion of pannus results in demineralisation and cystic resorption of underlying bone. Similar nodules may be found in the lung parenchyma, pleura, heart valves, myocardium and other internal organs. The characteristic histologic features are villous hypertrophy of the synovium and marked mononuclear inflammatory cell infiltrate in synovial membrane with formation of lymphoid follicles at places. Bacteria usually reach the joint space from the bloodstream but other routes of infection by direct contamination of an open wound or lymphatic spread may also occur. The common causative organisms are gonococci, meningococci, pneumococci, staphylococci, streptococci, H. The large joints of lower extremities such as the knee, hip and ankle, shoulder and sternoclavicular joints are particularly favoured sites. The process begins with hyperaemia, synovial swelling and infiltration by polymorphonuclear and mononuclear leucocytes along with development of effusion in the joint space. Another route of infection is direct spread from tuberculous osteomyelitis close to the joint. Most commonly involved sites are the spine, hip joint and knees, and less often other joints are affected. Grossly, the affected articular surface shows deposition of greyyellow exudate and occasionally tubercles are present. The underlying arti cular cartilage and bone may be involved by extension of tuberculous granulation tissue and cause necrosis (caries). Recurrent attacks of characteristic type of acute arthritis in which crystals of monosodium urate monohydrate may be demonstrable in the leucocytes present in the synovial fluid. Clinically, the natural history of gout comprises 4 stages: asymptomatic hyperuricaemia, acute gouty arthritis, asymptomatic intervals of intercritical periods, and chronic tophaceous stage. A serum uric acid level in excess of 7 mg/dl, which represents the upper limit of solubility of monosodium urate in serum at 37°C at blood pH, is associated with increased risk of development of gout. There is either an accelerated rate of purine biosynthesis de novo, or an increased turnover of nucleic acids. The causes of primary metabolic gout include a number of specific enzyme defects in purine metabolism which may be either of unknown cause or are inborn errors of meta bolism. Altered renal excretion could be due to reduced glomerular filtration of uric acid, enhanced tubular reabsorption or decreased secretion. The mechanism of acute inflam mation appears to include phagocytosis of crystals by leucocytes, activation of the kallikrein system, activation of the complement system and uratemediated disruption of lysosomes within the leucocytes leading to release of lysosomal products in the joint effusion. Initially, there is monoarticular involvement accompanied with intense pain, but later it becomes polyarticular along with constitutional symptoms like fever. Chronic tophaceous arthritis Recurrent attacks of acute gouty arthritis lead to progressive evolution into chronic arthritis. There is an acute inflammatory response and deposits of rhomboid crystals on the articular cartilage, ligaments, tendons and joint capsule, termed chondrocalcinosis. Histologically, it is well encapsulated and is composed of sheets of small oval to spindleshaped cells, foamy xanthoma cells, scattered multinucleate giant cells and irregular bundles of collagen. Pigmented villonodular tenosynovitis this is a diffuse form of synovial overgrowth seen most commonly in the knee and hip. Histologically, the bursal wall is composed of dense fibrous tissue lined by inflammatory granulation tissue. The wall is infiltrated by lymphocytes, plasma cells and macrophages and may show focal calcium deposits. Rheumatoid arthritis is a chronic multisystem disease of unknown cause occurring in 3rd to 4th decade of life commonly in women. It occurs in immunogenetically predisposed individual to the effect of some microbial infection as trigger event. Suppurative arthritis is an acute inflammatory involve ment of the joint by bacteria, usually from the bloodstream. Individual muscle fibre is an elongated multinucleated syncytiumlike cell about 100 µm in diameter and several centimeters in length. The muscle nuclei are spindleshaped and lie at the periphery of fibre under the sarcolemma, the plasma membrane of muscle fibre. Myofilaments are of 2 types-myosin comprising thick filaments and actin constituting thin filaments. These together produce crossstriations in muscle fibres seen in longitudinal sections on light microscopy. The condition presents clinically with muscular weakness and fatiguability, initially in the ocular musculature but later spreads to involve the trunk and limbs. These changes result in decreased neuromuscular transmission leading to failure to trigger muscle action potentials and consequent weakened muscle contraction. The exact mechanism how autoimmune response is initiated is not completely understood but the thymus appears to play a role in this process (page 369). The most common of these is myasthenia gravis; others are congenital myasthenia, an acquired Eaton Lambert syndrome associated with carcinoma of the lung, and denervation atrophy. Electron microscopy reveals reduction in synaptic area of the motor axons due to flattening or simplification of postsynaptic folds. The clinical manifestations of denervation atrophy are combination of muscular weakness and reduced muscle bulk. These are divided into 5 broad groups: hereditary (muscular dystrophies), inflammatory, endocrine, metabolic and toxic myopathies. Only the hereditary myopathies, also termed muscular dystrophies, are briefly considered below. Although soft tissue tumours may arise anywhere in the body but in general more common locations are lower extremity (40%), upper extremity (20%), trunk and retroperitoneum (30%) and head and neck (10%). Molecular and cytogenetic studies in many soft tissue tumours reveal chromosomal abnormalities and mutations in genes which can be used as a marker for diagnosis and histogenesis. Most of the soft tissue tumours occur sporadically; however, there are a few examples which are components of genetic syndromes. Thus, soft tissues included for the purpose of categorisation of these tumours are: fibrous tissue, adipose tissue, muscle tissue, synovial tissue, blood vessels and neuroectodermal tissues of the peripheral and autonomic nervous system (Table 27. The metastatic rate in low-grade sarcomas is about 2-10% and in high-grade sarcomas is 20100%. A few examples of epithelial tumours such as small cell carcinoma and malignant carcinoid tumours enter in the differential diagnosis of small round cell tumours. Based on differential diagnosis made on routine morphology, the panel of antibody stains is chosen for applying on paraffin sections for staining. On the other hand, combinations of fibrous growth with other mesenchymal tissue elements are more frequent. Soft tissue tumours are divided into benign, intermediate (locally aggressive or rarely metastasising) and malignant. Histologically, the central region of the mass shows looselyarranged fibroblasts having high mitotic activity. Towards the periphery, there is presence of osteoid matrix and formation of woven mineralised bone with trapped skeletal muscle fibres and regenerating muscle (myogenic) giant cells. This is why the condition is also called pseudomalignant osseous tumour of the soft tissues. Depending upon the anatomic locations and the age group affected, fibromatoses are broadly grouped as under: A. Infantile or juvenile fibromatoses these include: fibrous hamartoma of infancy, fibromatosis colli, diffuse infantile fibromatosis, juvenile aponeurotic fibroma, juvenile nasopharyngeal angiofibroma and congenital (generalised and solitary) fibromatosis. It appears as a painless, nodular or irregular, infiltrating, benign fibrous subcutaneous lesion. Microscopically, various morphologic patterns may be seen but most common is a whorled or S-shaped pattern of fibroblasts present in oedematous background. However, plantar lesions are less common than palmar type and do not cause contractures as frequently as palmar lesions. The nodules are composed of fibrovascular tissue having plump, tightly-packed fibroblasts which have high mitotic rate.