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I. Ortega. Geneva College.

Essential fatty acids are unsaturated molecules that cannot be produced by the body and must therefore be included in the diet order indinavir 400 mg on line medications elderly should not take. The process results in the replacement of normal cells by fibroblasts and eventually purchase indinavir 400 mg with visa treatment 2nd degree heart block, the replacement of normal organ tissue by scar tissue Flatulence - excessive gas in the stomach and intestines Fluid retention – failure of the body to expel fluids normally discount indinavir 400 mg free shipping treatment resistant anxiety, occurring in kidney diseases, when the protein count of plasma falls below 4%, fluid cannot be attracted back into the blood stream and edema (swelling) occurs, retention of salt is another cause of fluid retention Fluorometer – a device for determining the amount of radiation produced by xrays. A device for adjusting a fluoroscope to establish the location of a target more accurately and to produce an undistorted image or shadow Focal – pertaining to the point of convergence of light rays or waves of sound, such as a focal infection is one occurring near a focus – as the cavity of a tooth Folliculitis – inflammation of a follicle, synonym would be acne, or inflammation of a puss filled follicle of the scalp resulting in irregular hair loss and scarring Fungi – a vegetable cellular organism that subsists on organic matter, such as bacteria and molds, many species are parasitic, thus disease, fungi are simple dependent plants, lacking chlorophyll, with simple life cycles including toadstools, molds, mushrooms, rusts, lichens, and yeasts Furunculosis – a condition resulting from furuncles or boils – a tender dome shaped skin lesion, typically caused by infection around a hair follicle with Staph aureus. When they first appear they are often superficial, but as they mature they form localized abscesses with 410 pus and necrotic debris at their core. Its extracts have been used medicinally in China for centuries and promoted as a memory aid. Its extracts and metabolites are antioxidants Glandular - pertaining to or the nature of the gland, treatment of the disease with endocrine glands of their extracts Glaucoma – disease of the eye characterized by an increase in the intra ocular pressure which results in atrophy of the optic nerve and blindness of two general types, primary which sets in without known cause, and secondary in which there is an increase in intra-ocular pressure due to other eye diseases, the acute type is accompanied by acute pain, the chronic type has an insidious Gliomas – an onset Glioma – a sarcoma (cancerous) of neurological origin; a neoplasm or tumor composed of neuroglia cells Glossitis – inflammation of the tongue Glutamate – a salt of glutamic acid that functions as the brain’s main excitatory neurotransmitter 411 Glycerol – a trihydric alcohol, present in chemical combination in all fats. It is made commercially by the hydrolysis of fats, especially during the manufacture of soap, and is used extensively as a solvent, a preservative, and an emollient in various skin diseases. The volume of erythrocytes (Red blood cells) packed by centrifuge in a given volume of blood. A substance that assists in or stimulates the production of blood cells Hematotoxicity – pertaining to septicemia or toxicity in the blood Hematuria – blood in the urine, urine may be slightly smokey, reddish or very red Hemianopia – blindness for one-half field of vision in one or both eyes 412 Hemiplegia – paralysis of only one half of the body, a brain lesion involving upper motor neurons and resulting in paralysis of the opposite side of the body Hemodialysis – process by which the blood is filtered through a machine when the body is unable to rid itself of natural body toxins for whatever reason Hemodynamics – a study of the forces involved in circulating blood through the body Hemoglobin – the iron containing pigment of red blood cells that carries oxygen from the lungs to the tissues Hemolytic anemia – pertaining to the breakdown of red blood cells to the point of being anemic Hemoptysis – expectoration (vomiting) of blood arising from hemorrhage of the larynx, trachea, bronchi, or lungs, attack sudden, salty taste, blood frothy, bright red Hemorrhage – abnormal discharge of blood, either external or internal, venous, arterial, or capillary from blood vessels into tissues into or from the body, venous blood is dark red, flow is continuous, arterial blood is bright red, flows in jets, capillary blood is of a reddish color, exudes from tissues Hepatic – pertaining to the liver Hepatitis – inflammation of the liver, virus, toxic origin, it is manifested by jaundice (yellowing of the skin or the whites of the eyes) and in some instances, liver enlargement, fewer and other systemic disorders are usually present Hepatobiliary – a combining word referring to the liver and the bile ducts Hepatocellular – pertaining to the cells of the liver Hepatomegaly – enlargement of the liver Herpes simplex – fever blisters, occurrence of clusters of blisters usually on the face (also may be on the genital area) marked by itching and localized pain, lesions will dry up in 10 - 14 days if left alone Hiatal hernia – protrusion of a portion of the stomach upward through the diaphragm. The condition occurs in about 40% of the population and most people display few, if any, symptoms. The major difficulty in symptomatic patients is gastro esophageal reflux, the backflow of acid contents of the stomach into the esophagus Hirsutism – condition characterized by excessive growth of hair or presence of hair in unusual places Histaminergic/histamine – a substance produced from the amino acid histidine, which causes dilation of blood vessels, increased secretion of acid by the stomach, smooth muscle constriction (in the bronchi), and mucus production, tissue swelling, 413 and itching (during allergic reactions) The release of histamine from mast cells is a major component of hypersensitivity reactions, including asthma Histoplasmosis – a systemic fungal, respiratory disease caused by Histoplasma capsulatum. The reservoir for this fungus is in soil with a high organic content and undisturbed bird droppings, especially that around old chicken houses, caves harboring bats, and starlings, blackbirds, and pigeon roosts. It involves a chemical decomposition in which a substance is split into simpler compounds by the addition or the taking up of the elements of water. This kind of reaction occurs extremely frequently in life processes Hydroxycorticosteroid – a powerful steroid that helps in the inflammation within the body during an episode of illness Hyperammonemia – an excess amount of ammonia in the blood or ammonia toxicity. Ammonia is produced in the intestinal tract by bacterial action Hyperbilirubinemia – an excessive amount of bilirubin in the blood. The condition is seen in any illness causing jaundice (yellowing of the skin or whites of the eyes), including diseases in which the biliary tree is obstructed, and those in which blood formation is ineffective Hypercalcemia – an excessive amount of calcium in the blood. The causes of this condition include primary hyperparathyroidism, Lithium therapy, cancers including solid tumors, Vitamin D intoxication, hyperthyroidism, Vitamin A intoxication, aluminum intoxication and milk-alkali syndrome Hypercapnea – an increased amount of carbon dioxide in the blood. Elevated levels of carbon dioxide in the blood result from inadequate ventilation or from massive mismatches between ventilation and perfusion and the blood. Some of the common symptoms are: dizziness, drowsiness, confusion, tremors, and twitching Hyperchloremia – an increase in the chloride content of the blood. Chloride is the major extracellular anion and contributes too many body functions including the maintenance of osmotic pressure, acid-base balance, muscular activity and the movement of water between fluid compartments. It is a frequent finding in many disease processes such as asthma, metabolic acidosis, pulmonary embolism, and pulmonary 415 edema, and also in anxiety-induced states. One way to do this is to have the patient breathe through only one nostril, with the mouth closed. Having the patient breathe in and out of a paper bag is discouraged, as it leads to hypoxemia. After the acute phase of the hyperventilation has been managed, the underlying cause of the problem must be determined. Hypnotic – pertaining to sleep or hypnosis, an agent which induces sleep or which dulls the senses, drugs which cause insensibility to pain by inhibiting afferent impulses or the central centers of the brain receiving sensory impressions, and thus causing partial or complete unconsciousness Hypochondriac – affected with a morbid interest in health and disease Hypoglycemia – deficiency of sugar in the blood, a condition in which there is a level less than 80, hyper function of the pancreas may cause it or injection of an excessive amount of insulin Hypokalemia – an abnormally low concentration of potassium in the blood Hypokinesia – decreased motor reactions to stimulus Hypomania – hypomania and excitement, with a moderate change in behavior Hyponatremia – a decreased concentration of sodium (salt) in the blood Hypophysis – the pituitary body or gland Hypotension – decrease of systolic and diastolic blood pressure below normal, deficiency in tone or tension, below a blood pressure of 90/50 is pathologic, if increased pressure is followed by decreased pressure can be a serious condition, if the systolic and the diastolic drops proportionately – the patient will respond to the administration of stimulants, hypotension causes an accumulation of blood in the veins and slows down the arterial current Hypothalamic – a portion of the diencephalons compromising the ventral wall of the third ventricle below the hypothalamic sulcus, source of the hormones vasopressin and oxytocin stored and released by the neural lobe of the hypophysis Hypothermia – having a body temperature below normal, an art of lowered body temperature, usually between 78 - 90 degrees, to reduce oxygen need during surgery (especially cardiovascular and neurological procedures) and in hypoxia, to reduce blood pressure and to remedy Hypothyroid – marked by insufficient thyroid secretions in the body resulting in diminished basal metabolism, intolerance of cold temperatures, fatigue, mental apathy, physical sluggishness, constipation, muscle aches, dry skin and hair, and coarsening of features. These symptoms are called myxedema 416 Hypotonia – reduced tension, relaxation of arteries, loss of tone of the muscles or intra-ocular pressure Hypoventilation – reduced rate and depth of breathing Hypovolemia– diminished blood supply Hypoxemia – decreased oxygen tension (concentration) in arterial blood, measured by arterial oxygen partial pressure (PaO2) values. Symptoms may include memory issues, balance, ambulation, depending which area of the brain is affected Infiltrates – to pass into or through a substance or a space. A shadow seen on a chest xray, and assumed to represent blood, pus, or other body fluids in the lung Influenza – an acute contagious respiratory infection marked by fevers, muscle aches, headaches, prostration, cough, and sore throat. The disease usually strikes during the winter Influx – a flowing in 417 Insomnia – chronic inability to sleep or sleep prematurely ended or interrupted by periods of wakefulness, may be caused by a heavy late meal, with some coffee or other stimulants, including sugar in any form, overtiredness, mental fatigue, worry, excitement, and principally the fear of being unable to sleep Interstitial – placed or lying between; pertaining to interstices or spaces within an organ or tissue Intestinal atony – lack of muscle tone in the intestine and failure to contract normally, causing a delay in movement of fecal debris to exit the intestine Intracellular – within the cell Intracerebral – within the cerebellum of the brain. It consists of two lateral hemispheres and a narrow middle portion called the vermis. The cerebellum is involved in synergic control of skeletal muscles and plays an important role in the coordination of voluntary movements. It receives afferent impulses but is not a reflex center in the usual sense; however, it may reinforce some reflexes and inhibit others. Although the cerebellum does not initiate movements, it interrelates with many brainstem structures in executing various movements, including maintaining proper posture and balance; walking and running; fine involuntary movements as required in writing, dressing, eating, and playing musical instruments; and smooth tracking movements of the eyes. The cerebellum controls the property of movement such as speed, acceleration, and trajectory Intra ocular pressure – pressure with in the eyeball Intrathecal – within the spinal canal; within a sheath Involutional - a rolling or turning inward – associated with senile, pre-senile types, and manic-depressive groups Iritis – inflammation of the iris of the eye associated with pain, lacrimation, photophobia, diminution of vision, the iris appears swollen, dull and muddy, and pupil is contracted, irregular and sluggish in reaction Irritable bowel – the way the bowel responds excessively to a stimulus – diarrhea may be increased Ischemia – a temporary deficiency of blood flow to any organ or tissue. The deficiency may be caused by diminished blood flow either through a regional artery or throughout the circulation 418 J Jaundice – a condition characterized by yellowness of the skin, white of eyes, mucous membranes and body fluids, due to deposition of bile pigments resulting from excess bilirubin in the blood, it may result from obstruction of bile passageways, excessive destruction of red blood cells, or disturbances in functioning of the liver cells K Keratitis – inflammation and ulceration of the cornea, which is usually associated with decreased visual acuity, Eye pain, tearing, and light sensitivity are the most common symptoms Ketogenic diet – diet is high in fat, adequate in protein, and has negligible amounts of carbohydrate. It was created to stimulate some of the metabolic effects of fasting, a state known to decrease seizures in some individuals. They seem to do well for 2 or 3 months, then the seizures begin to start in again. Ketones – normal metabolic products, B-hydroxylbutyric acid and aminoacetic acid, from which acetone may arise spontaneously. The two acids are products of lipid pyruvate metabolism, and are oxidized by the muscles. It is metabolized by bacteria in the colon with the production of organic acids and is used to treat constipation and the encephalopathy that develops in patients with advanced cirrhosis of the liver. The unabsorbed sugar produces diarrhea and the acid pH helps to contain ammonia in the feces Laryngeal edema – swelling of the larynx in the throat Laryngospasm - spasm of the larynx in the throat Lavage – washing out of a cavity, example the eye or the abdomen abdomen Lecithin – any of a group of phospholipids common in plants and animals. They are found in the liver, nerve tissue, semen, and in smaller amounts in bile and blood. They are essential in the metabolism of fats and are used in the processing of foods, pharmaceuticals products, cosmetics, and inks. Deficiency leads to hepatic and renal disorders, high serum cholesterol levels, atherosclerosis, and arteriosclerosis Lennox-Gestaut - blanket term covering a variety of seizures (atonic drop attacks, complex partial, absence, and occasional tonic clonic) associated with significant delay in motor and intellectual development and does not respond well to drugs Lens – a transparent refractory as in the lens of the eye Lethargy – a condition of functional sluggishness, stupor, a state similar to hypnosis, or the first stage of hypnotism Leukocytosis – an increase in the number of leukocytes in the blood. It occurs most commonly in disease processes involving infection, inflammation, trauma, or stress, but it also can result occasionally from the use of some medications Leukopenia – abnormal decrease of white blood cells usually below 5000. A great number of drugs may cause leucopenia, as can failure of the bone marrow Leukorrhea – a white estrogen related scant/moderate odorless physiological vaginal discharge, normally preceding menarche and occurring during ovulation, during pregnancy, and in response to sexual excitement. Some women note an increased discharge related to oral contraceptive or hormone replacement therapy. Chronic cervicitis and vaginal infections are the most common causes of abnormal genital discharge. Signs of infection include increased discharge, change in color and consistency, odor, vulvar irritation, dysuria, and itching Limbic – the edge or border of a part, the margin Lipase – a fat splitting enzyme found in the blood, pancreatic secretion and tissues 420 Liposome – the recycling center of the cell where large molecules are broken down into small molecules to be reused kidney shaped organs of lymphoid tissues that lie at intervals along the lymphatic vessels Lupus Erythematous - tubercular skin disease, acute or subacute circulatory disorders and trauma predispose, reddish brown soft patches, circumscribed with raised edges and depressed centers which are white and scar like when scales drop off, disease spreads slowly, middle life females are predisposing factors. A chronic autoimmune inflammatory disease involving multiple organ systems and marked by periodic acute episodes. The disease is more prevalent is women of childbearing ages Lymphadenopathy – disease of the lymph nodes Lymphocyte – a white blood cell responsible for much of the body’s immune protection. Fewer than 1% are present in the circulating blood; the rest lie in the lymph nodes, spleen, and other lymphoid organs, where they can maximize contact with foreign antigens Lymph nodes – one of thousands of small kidneyed shaped organs of lymphoid tissue that lie at intervals along the lymphatic vessels Lysis – the gradual decline of a fever or disease; the opposite of crisis.

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Sinuses and Nasal Cavity These cancers are rare buy 400 mg indinavir medicine 5325, and most are squamous cell cancers 400 mg indinavir with mastercard medications you can buy in mexico. Salivary Glands Cancers of the salivary glands can arise in major glands (including the parotid indinavir 400 mg mastercard medications 5 rights, submandibular, and sublingual) and minor glands. Malignant tumors of the parotid gland are treated with total parotidectomy with preservation of the facial nerve, unless the nerve is involved directly. If the cancer is “high grade,” selective or modified radical neck dissection is added, then usually followed by postoperative radiation therapy. The preepiglottic space is that area anterior to the epiglottis bordered by the hyoid bone superiorly and the thyrohyoid membrane and superior rim of the thyroid cartilage anteriorly. Whether to remove all or most of the thyroid gland has been controversial (Tables 11. Weigel’s chapter on thyroid surgery in Surgery: Basic Science and Clin- ical Evidence, edited by J. T4 Consider whole body scan in 1–2 years Papillary cancer, thyroglobulin less than 5, scan probably Surgical follow-up unnecesary Endocrine follow-up Algorithm 11. The majority of thyroid cancers are the papillary type, Even those lesions classified as “follicular” will behave similar to “papillary” lesions if papillary elements are identified. The final pathology report for our patient was available in the after- noon of the first postoperative day. The surgeon discussed the case with you and advised returning the patient to the operating room for completion total thyroidectomy. The patient had been forewarned about this pos- sibility and reentered the hospital for the procedure, which was carried out without complication 72 hours after the first operation. Papillary thyroid carcinomas are highly curable, spreading locally and into nearby lymph nodes before becoming blood-borne and metastatic to lung, bone, or other sites. Residual disease or metastases usually can be controlled using radioactive iodine (131I); chemotherapy is not effective. Most often, the surgeon does a total thyroidectomy, per- forming a lymph node dissection only when metastases are identified; modified radical neck dissection preserves the sternocleidomastoid muscle, spinal accessory nerve, and jugular vein while cleaning out the lymph nodes lateral to the thyroid and along the trachea. For follicular cancers, the surgical approach is similar; however, these lesions are more likely to spread via the bloodstream and are not as easily controlled with 131I when metastatic. Anaplastic carcinomas are rare thyroid neoplasms that are highly aggressive, extensive (almost impossible to remove), and resistant to therapy. The surgical approach is to try to clear the anterior wall of the trachea and remove all cancer locally, if possible; tracheostomy may be necessary. More recently, the ret proto-oncogene has been used to determine the presence of this cancer prior to changes in the calcitonin levels, allowing even earlier surgical intervention. The surgical approach is aggressive, consisting of total thyroidectomy with meticulous “central compartment” dissection and ipsilateral modified radical neck dissection. In determining the management of papillary and follicular thyroid cancer, the relative risk of recurrence and death is evaluated so as to plan the most effective treatment. In patients with thyroid cancer, a man over 40, a woman over 50, and anyone with distant metastases or cancer involving both lobes or invading adjacent tissues is classified as “high risk. Involvement of one or two nearby lymph nodes may increase the risk slightly but does not have the same significance 198 J. These patients should be fol- lowed with periodic neck examinations and determination of the serum thyroglobulin levels. A very low thyroglobulin level is evidence against papillary cancer (or “Hürthle cell cancer”) recurrence. These patients present with high serum calcium levels and usually a hard mass in the neck. Perils and Pitfalls In any surgery of or near the thyroid, there is a risk of temporary or permanent injury to the recurrent laryngeal nerve and to the exter- nal branch of the superior laryngeal nerve. Removing or destroying too much parathyroid tissue carries the risk of producing severe hypoparathyroidism, which is difficult to manage and very unpleas- ant for the patient. An extremely important complication, because it is life threatening, is an unrecognized postoperative compression of the trachea from an expanding hematoma after thyroid surgery. When called to see a postop- erative thyroid patient who has difficulty breathing, the responding physician must not hesitate to open the incision and spread the closed muscles to relieve the pressure on the trachea by releasing the trapped blood. Summary An overview of this complex topic has stressed diagnostic techniques, lesions, and cancers most frequently encountered in the head and neck. Appropriate referral, careful evaluation, and biopsy of suspicious lesions has been encouraged. We have stressed the need for careful, logical progression from detailed history-taking to choice of appropriate diagnostic testing, only after careful physical examination. Oropharyngeal and neck lesions, in smokers, are especially worrisome because of the greatly increased risk of cancer in these individuals. Abnormalities of the thyroid cause most lumps of the neck that trigger a visit to a physician’s office. Relative contribution of tech- netium-99m sestamibi scintigraphy, intraoperative gamma probe detection, and the rapid parathyroid hormone assay to the surgical management of hyperparathyroidism. Thyroid carcinoma: biological implications of age, method of detection, and site and extent of recurrence. To discuss the anatomy and physiology of the swallowing structures and mechanism, including the physiologic lower esophageal sphincter. To discuss pertinent clinical history and physical examination findings as they relate to structural and functional pathology. To describe various therapeutic options for patients with neurologic, neoplastic, reflex- mediated, and dysmotility-mediated disorders. Cases Case 1 A 58-year-old man presents to your office complaining of difficulty in swallowing. Case 2 A 39-year-old woman presents to your office with burning chest pain, rapidly worsening over 3 years. Case 3 A 72-year-old woman presents to your office with difficulty in swal- lowing for decades. Swallowing Difficulty and Pain 201 Introduction The swallowing mechanism is a complex interaction of pharyngeal and esophageal structures designed for the seemingly simple purpose of propelling food to the stomach and of allowing the expulsion of excess gas or potentially toxic food out of the stomach. Initial evaluation of a patient complaining of difficulty (dysphagia) or pain (odynophagia) with swallowing involves a thorough, focused history and a physical examination. The advent of esophageal motility and pH studies has permitted correla- tion of physiologic data to the anatomic information obtained through radiographic and endoscopic studies. Others may only confuse the diagnosis, having no relationship to the patient’s complaints. In evaluating swallowing difficulty and pain, it is extremely important to relate symptoms to diagnosis, as inappropri- ate therapy actually may worsen the patient’s symptoms or initiate new complications.

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This concept order indinavir 400 mg overnight delivery symptoms exhaustion, still reflected in terms such as “swamp fever” or “malaria order 400 mg indinavir with amex medications ending in pam,” was the predominant academic opinion until the end of the 19th century cheap 400 mg indinavir free shipping medicine 2016, despite the fact that the Dutch cloth merchant A. At the time, general acceptance of the notion of “spontaneous generation”—creation of life from dead organic material—stood in the way of implicating the bacteria found in the corpses of infection victims as the cause of the deadly diseases. It was not until Pas- teur disproved the doctrine of spontaneous generation in the second half of the 19th century that a new way of thinking became possible. By the end of that century, microorganisms had been identified as the causal agents in many familiar diseases by applying the Henle-Koch postulates formulated by R. The History of Infectious Diseases 3 The Henle–Koch Postulates 1 The postulates can be freely formulated as follows: & The microorganism must be found under conditions corresponding to the pathological changes and clinical course of the disease in question. However, the fact that these conditions are not met does not necessarily exclude a contribution to disease etiology by a pathogen found in context. In particular, many infections caused by subcellular entities do not fulfill the postulates in their classic form. The Present The frequency and deadliness of infectious diseases throughout thousands of years of human history have kept them at the focus of medical science. The development of effective preventive and therapeutic measures in recent dec- ades has diminished, and sometimes eliminated entirely, the grim epidemics of smallpox, plague, spotted fever, diphtheria, and other such contagions. As a result of these developments, the attention of medical researchers was diverted to other fields: it seemed we had tamed the infectious diseases. Previously unknown pathogens causing new diseases are being found and familiar organisms have demonstrated an ability to evolve new forms and reassert themselves. The origins of this reversal are many and complex: human behavior has changed, particularly in terms of mobility and nutrition. Further contributory factors were the in- troduction of invasive and aggressive medical therapies, neglect of estab- lished methods of infection control and, of course, the ability of pathogens to make full use of their specific genetic variability to adapt to changing con- ditions. The upshot is that physicians in particular, as well as other medical professionals and staff, urgently require a basic knowledge of the pathogens involved and the genesis of infectious diseases if they are to respond effec- tively to this dynamism in the field of infectiology. Prokaryotic and Eukaryotic Microorganisms According to a proposal by Woese that has been gaining general acceptance in recent years, the world of living things is classified in the three domains bac- teria, archaea, and eucarya. In this system, each domain is subdivided into Kayser, Medical Microbiology © 2005 Thieme All rights reserved. This domain includes the kingdom of the heterotrophic eubacteria and includes all human pathogen bacteria. The other kingdoms, for instance that of the photosynthetic cyanobacteria, are notpathogenic. It is estimated that bacterial spe- cies on Earth number in the hundreds of thousands, of which only about 5500 have been discovered and described in detail. This domain includes forms that live under extreme environmental con- ditions, including thermophilic, hyperthermophilic, halophilic, and methanogenic microorganisms. The earlier term for the archaea was archaebacteria (ancient bac- teria), and they are indeed a kind of living fossil. Thermophilic archaea thrive mainly in warm, moist biotopes such as the hot springs at the top of geothermal vents. The hyperthermophilic archaea, a more recent discovery, live near deep-sea volcanic plumes at temperatures exceeding 1008C. The plant and animal kingdoms (animales and plantales) are all eukaryotic life forms. These organisms are obligate intracellular parasites that are able to reproduce in certain human cells only and are found in two stages: the infectious, nonreproductive particles called elementary bodies (0. These organisms are obligate intracellular parasites, rod- shaped to coccoid, that reproduce by binary transverse fission. Theyare found in a wide variety of forms, the most common being the coccoid cell (0. Fungi (Mycophyta) are nonmotile eukaryotes with rigid cell walls and a classic cell nucleus. They contain no photosynthetic pigments and are carbon heterotrophic, that is, they utilize various organic nutrient substrates (in contrast to carbon autotrophic plants). Of more than 50 000 fungal spe- cies, only about 300 are known to be human pathogens. Protozoa are microorganisms in various sizes and forms that may be free-living or parasitic. They possess a nucleus containing chromo- somes and organelles such as mitochondria (lacking in some cases), an en- Kayser, Medical Microbiology © 2005 Thieme All rights reserved. Host–Pathogen Interactions 7 doplasmic reticulum, pseudopods, flagella, cilia, kinetoplasts, etc. Many para- sitic protozoa are transmitted by arthropods, whereby multiplication and 1 transformation into the infectious stage take place in the vector. Medically signif- icant groups include the trematodes (flukes or flatworms), cestodes (tape- worms), and nematodes (roundworms). These animals are characterized by an external chitin skele- ton, segmented bodies, jointed legs, special mouthparts, and other specific features. Their role as direct causative agents of diseases is a minor one (mites, for instance, cause scabies) as compared to their role as vectors trans- mitting viruses, bacteria, protozoa, and helminths. Host–Pathogen Interactions & The factors determining the genesis, clinical picture and outcome of an infection include complex relationships between the host and invading or- ganisms that differ widely depending on the pathogen involved. Despite this variability, a number of general principles apply to the interactions be- tween the invading pathogen with its aggression factors and the host with its defenses. Since the pathogenesis of bacterial infectious diseases has been re- searched very thoroughly, the following summary is based on the host–in- vader interactions seen in this type of infection. The determinants of bacterial pathogenicity and virulence can be outlined as follows: & Adhesion to host cells (adhesins). The above bacterial pathogenicity factors are confronted by the following host defense mechanisms: & Nonspecific defenses including mechanical, humoral, and cellular sys- tems. The response of these defenses to infection thus involves the correlation of a number of different mechanisms. Primary, innate defects are rare, whereas acquired, sec- ondary immune defects occur frequently, paving the way for infections by microorganisms known as “facultative pathogens” (opportunists). The terms pathogenicity and virulence are not clearly defined in their relevance to microorganisms. It has been proposed that pathogenicity be used to characterize a particular species and that virulence be used to describe the sum of the disease-causing properties of a population (strain) of a pathogenic species (Fig. Determinants of Bacterial Pathogenicity and Virulence Relatively little is known about the factors determining the pathogenicity and virulence of microorganisms, and most of what we do know concerns the disease-causing mechanisms of bacteria. Host–Pathogen Interactions 11 Virulence, Pathogenicity, Susceptibility, Disposition 1 virulent strain avirulent type or var (e. The terms disposi- tion and resistance are used to characterize the status of individuals of a suscep- tible host species.

Of course order indinavir 400mg with amex medications names and uses, with almost all the systems presently used safe indinavir 400 mg in treatment online, this situation does not arise as the designated application is such that significant amounts of the “payload” remain in the device when it is replaced with a fresh system purchase indinavir 400 mg amex medicine technology. However, it is not inconceivable that such depleting systems may become more common in the future, especially for drug substances which are exquisitely potent or expensive or potentially subject to abuse. Scopolamine Scopolamine was the first drug to be marketed as a transdermal delivery system (Transderm-Scop) to alleviate the discomfort of motion sickness. After oral administration, scopolamine has a short duration of action because of a high first-pass effect. In addition, several side-effects are associated with the peak plasma levels obtained. Transderm-Scop is a reservoir system that incorporates two types of release mechanims: a rapid, short-term release of drug from the adhesive layer, superimposed on an essentially zero-order input profile metered by the microporous membrane separating the reservoir from the skin surface. The scopolamine patch is able to maintain plasma levels in the therapeutic window for extended periods of time, delivering 0. Nitroglycerin This drug has been used to treat angina pectoris for over 100 years. It is a potent compound with a high clearance (266 L/hr), short half-life (1–4 minutes) and extremely low oral bioavailability (<1%). Percutaneous transport of mtroglycerin is relatively efficient, and conventional ointment formulations were the first modern-day transdermal formulations available. In the early 1980s, however, three patches appeared more or less simultaneously (Transderm-Nitro NitroDisc, and NitroDur), and transdermal delivery became widely recognized as an alternative route of administration for appropriate drugs. Since that time, numerous new and modified patches have been approved which differ considerably in design, composition, drug loading and release mechanism. Nevertheless, it is possible to demonstrate a bioequivalence between these patches, in terms of the resulting plasma concentration versus time profiles (Figure 8. When nitroglycerin is delivered via the skin, a sustained concentration can be achieved over an extended period of time. This profile contrasts sharply with those obtained following administration of sublingual and ointment 205 Figure 8. Despite this apparently clear pharmacokinetic advantage, however, it turns out that zero- order delivery of nitroglycerin for 24 hours, on a chronic basis, poses a pharmacodynamic problem: namely, tolerance. That is, even though the delivered amount of drug per unit time remains constant, the pharmacological effect of the drug decreases progressively, to the point that there is essentially no benefit to the patient. The problem is resolved by imposing a drug-free period during each dosing interval of 24 hours. Thus, presently, the patches are applied in the morning, after showering, and worn for 12–16 hours, with a “resting” or wash-out period overnight when patients are less susceptible (although not immune) to angina attacks. The drug has a relatively long half-life (6–20 h) and a modest clearance (13 L h−1). The rationale for the development of transdermal clonidine was to reduce side-effects and to improve patient compliance. The control of drug delivery over 7 days is impressive, and avoids the “peaks and valleys” of2 conventional (twice-a-day) oral administration (Figure 8. However, this system has not achieved as wide a success as first seemed likely because of skin sensitization. Clonidine itself, when administered transdermally on a chronic, repetitive basis, induces in a significant fraction of patients a classic immunologic skin reaction, and this has severely attenuated its use. Estmdiol Transdermal estradiol is indicated for postmenopausal hormone replacement therapy. Estradiol is a potent, high clearance (600– 800 L/hr) and short half-life (1 hr) drug. Due to the very high hepatic first-pass effect, conventional oral hormone replacement therapy results in an artificially elevated and, in the long 206 Figure 8. Transdermal delivery of estradiol, however, results in sustained plasma concentrations over several days (Figure 8. Pharmacologically, beneficial effects on the frequency of hot flushes, sleep disturbance, irritability and mental accuity have been documented. More recently, other simpler, and more elegant, monolithic systems have reached the market, and perform as well as, if not better than, the original system. Because the postmenopausal woman is usually treated concomitantly with an oral progestin (i. One of the first of these systems containing estradiol and levonorgestrel has recently been approved for marketing. Fentanyl This very powerful analgesic had been limited to parenteral use during and after surgery. Accurate dose titration is necessary because of the drug’s very narrow therapeutic window (1–2 ng mL−1). The potential of fentanyl, however, to significantly improve the treatment of acute post-operative pain and chronic cancer pain provoked the development of the now-approved Duragesic transdermal system. This reservoir system can be used for up to 3 days and is available in four “doses” (10, 20, 30 and 40 cm delivering, respectively, 25,2 50, 75 and 100 µg hr−1). Nicotine 207 Nicotine is generally believed to be the principal addictive component in tobacco. Patches containing nicotine are targeted at smoking cessation and compete with other nicotine-based systems, including chewing gum, lozenges and a nasal spray. Nicotine has a relatively short half-life (2 hr) and high clearance (78 L hr−1), which means that nicotine replacement via the gum, for example, requires almost constant chewing of about 10 pieces per day to match the bioavailability of the “drug” achieved by smoking one cigarette per hour. Transdermal delivery, therefore, was designed to provide sustained input over the course of 24 hours (or, in the case of one system, for ~16 hours—the argument being that not even the heaviest smoker lights up when asleep! Several patches reached the market (such as Nicotrol, Nicoderm, Prostep and Habitrol) representing examples of each of the basic system designs, and all of which are pharmacokinetically bioequivalent. There are differences, though, in the degree of irritation induced by the different patches and this seems to be related to the relative thermodynamic activity of nicotine in the different systems. Drug loading also varies appreciably between the different patches, as does the efficiency of drug usage. Short- term efficacy has been established by showing that the use of the patches reduces tobacco withdrawal symptoms and increases abstinence. Longer-term studies reveal that the patches can be effective but require supplemental pyschological and motivational aid and counseling to minimize the chances that a subject returns to smoking. Recently, in many countries, nicotine patches have become available “over the counter” without a prescription. Testosterone These patches (Testoderm, Testoderm with Adhesive, and Androderm) are approved for the treatment of hormonal insufficiency in diseases such as primary hypogonadism and hypogonadotropic hypogonadism. The systems are applied daily to mimic the endogenous profile of serum testosterone in the normal male. Testoderm (4 mg and 6 mg) and Testoderm with Adhesive (6 mg) release controlled amounts of testosterone upon daily application to scrotal skin. These systems have contact areas of 40 or 60 cm, and2 contain 10 and 15 mg of testosterone, respectively. The matrix system, Androderm, also provides continuous delivery of testosterone for 24 hours, but is applied to non-scrotal skin. Permeation enhancers are essential for this patch to ensure the efficient delivery of drug through skin sites which are less permeable than scrotal skin.

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