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O. Hengley, M.A., Ph.D.

Deputy Director, VCU School of Medicine, Medical College of Virginia Health Sciences Division

These genes have been cloned into plasmids and expressed in large quantities to produce these proteins as drugs. Expression of the gene and its protein in the vaccinated person will lead to the development of an immune response. Bacteria have traits that enable them to enter (invade) the environment, remain in a niche (adhere or colonize), gain access to food sources (degradative enzymes), sequester ions. When sufficient numbers of bacteria are present (quorum), they turn on functions to support the colony, including production of a biofilm. Unfortunately, many of the mechanisms bacteria use to maintain their niche and the byproducts of bacterial growth. Many of these traits are virulence factors that enhance the ability of bacteria to cause disease. Although many bacteria cause disease by directly destroying tissue, some release toxins, which are then disseminated by the blood to cause systemwide pathogenesis (Box 14-1). Production of disease results from the combination of damage caused by the bacteria and the consequences of the innate and immune (inflammation) responses to the infection (Box 14-2). Not all bacteria or bacterial infections cause disease; however, some always cause disease. The human body is colonized with numerous microbes (normal flora), many of which serve important functions for their hosts. The composition of the normal flora can be disrupted by antibiotic treatment, diet, stress, and changes in the host response to the flora. An altered normal flora can lead to inappropriate immune responses, causing inflammatory bowel diseases. Normal flora bacteria cause disease if they enter normally sterile sites of the body. Opportunistic bacteria take advantage of preexisting conditions, such as immunosuppression, to grow and cause serious disease. Disease results from the damage or loss of tissue or organ function due to the infection or the host inflammatory responses. The signs and symptoms of a disease are determined by the change to the affected tissue. Systemic responses are produced by toxins and the cytokines produced in response to the infection. The seriousness of the disease depends on the importance of the affected organ and the extent of the damage caused by the infection. The bacterial strain and inoculum size are also major factors in determining whether disease occurs; however, the threshold for disease production is different for different bacteria. For example, although a million or more Salmonella organisms are necessary for gastroenteritis to become established in a healthy person, only a few thousand organisms are necessary in a person whose gastric pH has been neutralized with antacids or other means. The longer a bacterium remains in the body, the greater its numbers, its ability to spread, and its potential to cause tissue damage and disease, and the larger the host response. Many of the virulence factors consist of complex structures or activities that are only expressed under special conditions (see Figure 13-6). The components for these structures are often encoded together in a pathogenicity island. Pathogenicity islands are large genetic regions in the chromosome or on plasmids that contain sets of genes encoding numerous virulence factors that may require coordinated expression. A pathogenicity island is usually within a transposon and can be transferred as a unit to different sites within a chromosome or to other bacteria. Disease is caused by damage produced by the bacteria plus the consequencesofinnateandimmuneresponsestotheinfection. Thelengthoftheincubationperiodisthetimerequiredforthebacteria and/or the host response to cause sufficient damage to initiate discomfortorinterferewithessentialfunctions. On invasion, the bacteria can travel in the bloodstream to other sites in the body. The skin has a thick, horny layer of dead cells that protects the body from infection. However, cuts in the skin, produced accidentally or surgically or kept open with catheters or other surgical appliances, provide a means for the bacteria to gain access to the susceptible tissue underneath.

Diseases

• Barbiturate overdose
• Renal dysplasia mesomelia radiohumeral fusion
• Bilateral renal agenesis
• Angioma hereditary neurocutaneous
• Holoprosencephaly ectrodactyly cleft lip palate
• Morrison Young syndrome
• Sialidosis
• Brachydactyly clinodactyly

Simple vulvovaginal candidiasis is not accompanied by systemic symptoms such as fever and muscle aches. Metronidazole is used to treat infections caused by protozoa and anaerobic bacteria, including Trichomonas vaginalis and bacterial vaginosis. Infection with T vaginalis presents with a malodorous, frothy green discharge, vaginal pruritus, and erythema. Bacterial vaginosis, which is usually due to Gardnerella vaginalis infection, presents with perivaginal inflammation and irritation, dysuria, dyspareunia, and a grayish discharge with a "fishy" odor. Neither illness is usually accompanied by systemic symptoms or demarcated vaginal lesions as seen in the image. A syphilitic chancre, indicative of primary syphilis, is usually a solitary, painless, 1- to 2-cm papule with an indurated base. The oral form is associated with hemolytic anemia and headache, and the aerosolized form is associated with bronchospasm, rash, and conjunctival irritation. This patient is presenting with acute mental status changes and seizures secondary to severe hyponatremia. While it is certainly possible to become hyponatremic from excessive fluid intake (polydipsia), one would not expect to see a hyponatremia of this severity purely from drinking too much fluid. This would lead to water loss from the kidneys to compensate, and thus serum osmolality should not decrease. A new-onset seizure in an older adult always raises concern for a primary brain process, especially tumor. So while both are certainly possible, small cell lung cancer is much more likely in this patient. Mental status changes and seizures always raise concern for pathology occurring in the brain, in particular spaceoccupying lesions such as tumors. While squamous cell lung cancer is clearly associated with smoking, the paraneoplastic syndrome it presents with is usually the secretion of a parathyroid-like peptide, which causes signs and symptoms relating to the resultant hypercalcemia, such as fatigue, depression, muscle weakness, abdominal pain, nausea, and constipation. Degraded tetracycline is associated with Fanconi syndrome, a disorder of proximal tubule function that results in severe loss of protein, glucose, and essential minerals (especially calcium and magnesium). Patients present with symptoms of polydipsia, polyuria, and dehydration due to excess loss of water and solutes in their urine. Acute tubular necrosis is typically associated with hypoperfusion and is not associated with either Fanconi syndrome or tetracycline. Glomerulonephritis is most often caused by immune complex deposition and is not associated with either Fanconi syndrome or tetracycline. Kidney stones, commonly caused by hypercalciuria or infection, are not associated with either Fanconi syndrome or tetracycline. Renal papillary necrosis, often caused by diabetes or acute pyelone- phritis, is not associated with either Fanconi syndrome or tetracycline. Renal papillary necrosis can be caused by an overdose of analgesics such as aspirin, phenacetin, and acetaminophen. Necrosis results from a combination of decreased blood flow to the kidney, consumption of antioxidants, and subsequent oxidative damage. Histrionic personality disorder is one of the cluster B personality disorders (the "wild" group) that presents early in adulthood. It is best characterized as a pattern of excessive emotionality and attention seeking, and it is often accompanied by somatoform disorders (somatization is a process by which an individual uses his or her body or symptoms for a range of psychologic purposes and gains). An especially important characteristic to remember about histrionic personality disorder is the often overtly sexual nature of those affected. Type 1 bipolar disorder is characterized by manic episodes (periods of elevated or irritable mood that must last at least one week) as well as depressive syndromes and mixed syndromes. Sleep of sevennine hours per night is not usually consistent with a manic syndrome. Obsessive-compulsive personality disorder is characterized by an excessive preoccupation with control, order, and perfectionism. Paranoid personality disorder is characterized by the inherent belief that the world is a dangerous and threatening place. Upon meeting these individuals they often project strength and capability, and their distrust and suspiciousness of everyone is evident. Schizotypal personality disorder is characterized by interpersonal awkwardness, odd beliefs or magical thinking, and an eccentric appearance.

Selective application of antifungal susceptibility testing, coupled with broader identification of fungi to the species level, is especially useful in difficult-to-manage fungal infections. One must keep in mind, however, that the in vitro susceptibility of an infecting organism to the antimicrobial agent is only one of several factors that may influence the likelihood that therapy for an infection will be successful (see Clinical Factors Contributing to Resistance). Describe the mechanisms of resistance to the azoles that are known for Candida albicans. The echinocandin antifungal agents inhibit the 1,3-glucan synthesis enzyme complex, resulting in deficient cell wall production. Because mammalian cells do not contain 1,3-glucans, this class of agents is selective in its toxicity for fungi. Most of the other systemically active antifungal agents act on targets that to some extent are shared by mammalian cells and thus may exhibit toxicity to the host as well as the infecting fungus. The attraction of combination therapy is that by using combinations of antifungal agents, one may be able to achieve a better clinical outcome than with monotherapy. Darrell has taken to giving Delbert frequent "smooches" on his muzzle, which Delbert loves because he knows a treat is soon to follow. After about 3 months of proud puppy ownership and "smooching," Darrell noticed that his mustache began itching, and his upper lip was beginning to swell. Over a 1-week period, his upper lip became swollen and inflamed, and small pustular areas became apparent among the sparse hairs of his moustache. The veterinarian took one look at the pair, wrote a prescription for Delbert, and told Darrell that he should make a visit to the dermatologist. These infections are generally categorized by the structures the fungi colonize or invade: 1. Cutaneous mycoses, infections that involve the deeper layers of the epidermis and its integuments, the hair and nails 3. Subcutaneous mycoses, involving the dermis, subcutaneous tissues, muscle, and fascia. Given the clinical and epidemiologic evidence, one might expect infection with a zoophilic pathogen such as Microsporum canis or a Trichophyton species. A specific etiologic diagnosis requires culture of hair and skin scrapings, followed by assessment of the gross and microscopic appearance of the cultured fungus. In the case of dermatophytes, further identification may be accomplished by assessing the nutritional requirements of the fungus using special dermatophyte test media. This infection, tinea barbae, will require therapy with an agent such as terbinafine or itraconazole. Infections caused by these organisms elicit little or no host immune response and are nondestructive and thus asymptomatic. Human infection is thought to result from direct or indirect transfer of infected keratinous material from one person to another. Clinical Syndromes the lesions of pityriasis versicolor are small hypopigmented or hyperpigmented macules. The upper trunk, arms, chest, shoulders, face, and neck are most often involved, but any part of the body may be affected (Figure 62-3). The lesions are irregular, well-demarcated patches of discoloration that may be raised and covered by a fine scale. In light-skinned individuals, the lesions are pink to pale brown and become more obvious when they fail to tan after exposure to sunlight. Little or no host reaction occurs, and the lesions are asymptomatic, with the exception of mild pruritus in severe cases. Pityriasis (Tinea) Versicolor Pityriasis versicolor is a common superficial fungal infection seen worldwide. The yeast cells may be mixed with short, infrequently branched hyphae that tend to orient end to end. The yeastlike cells represent phialoconidia and show polar bud formation with a "lip" or collarette around the point of bud initiation on the parent cell (Figure 62-2). In culture on standard media containing or overlaid with olive oil, species of the M.

Segmental sclerosis with hyalinosis is seen in focal segmental glomerulosclerosis. Glomeruli demonstrating a wire-loop appearance with subendothelial basement membrane deposits are seen in lupus nephropathy. However, burns of the depth described in the question stem could only be caused by a much longer duration of contact with hot water than the mother indicates. The physical findings suggest this child has been forcibly held in deeper, much hotter water, which suggests child abuse. Suspected child abuse requires further investigation by authorities once immediate attention to wounds is provided. The child needs to be treated for his wounds, and a full physical examination should be conducted to look for other signs of child abuse. In cases of suspected child abuse such as this one, the appropriate authorities must be contacted. This answer is incorrect because it does not reflect the need to contact the appropriate personnel. Intermittent headaches, sweating, and palpitations in an otherwise healthy man are suggestive of a pheochromocytoma, a catecholamine-secreting tumor most commonly found in the adrenal glands. Episodes are limited in duration, but blood pressure during these events can reach dangerously high levels. High urinary catecholamines, metanephrine, and vanillylmandelic acid confirm the diagnosis. During the initial phase of glandular injury, a transient state of hyperthyroidism may result from cellular rupture. Prolactinomas cause excessive secretion of prolactin, resulting in secondary amenorrhea in women and galactorrhea. It typically has a relapsing-remitting course and is most commonly seen in female patients with peak age of onset between 20 and 40 years. Another common presentation is visual loss secondary to optic neuritis and unilateral shooting facial pain secondary to trigeminal neuralgia. These lesions appear as "finger like" projections around the ventricles and are easiest to see with a sagittal image. Interferon beta-1a is indicated for the long-term treatment of patients with relapsing forms of the disease to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. The patient presents with trigeminal neuralgia in the setting of several other past neurologic complaints. While trigeminal neuralgia is characterized by unilateral shooting facial pains, it is important to distinguish this pain from that of a headache (eg, migraine, cluster, or tension). Heparin would be an appropriate therapeutic intervention in the case of an ischemic stroke. Moreover, the patient is quite young and an ischemic stroke in such a young patient would be exceedingly rare. Triptans are used as initial treatment in the case of cluster and migraine headache. A 6-year-old boy was brought to a pediatrician two weeks ago because his teacher noticed he had begun "blanking out" in the classroom, staring into space, failing to respond to his name, and occasionally drooling. A 30-year-old man presents with a sevenmonth history of fatigue, weight loss, depression, and abdominal pain worsened by eating. He recently experienced two episodes of kidney stones, which he has never had before, and reports decreased libido over the past couple years. He was adopted at an early age, has no children, and is unsure of his family history. A 29-year-old woman presents to the obstetrician-gynecologist with complaints of amenorrhea for the past two months. She notes that she is sexually active with her boyfriend of six months, and they do not use any form of contraception. She is worried about pregnancy, despite several negative home pregnancy tests a few days ago.