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Diphtheria

Diphtheria

Diphtheria is an upper respiratory tract illness characterized by sore throat, low-grade fever, and an adherent membrane of the tonsil(s), pharynx, and/or nose. A milder form of diphtheria can be limited to the skin. It is caused by Corynebacterium diphtheriae, an aerobic Gram-positive bacterium. Diphtheria is a highly contagious disease spread by direct physical contact or breathing the secretions of those infected. Diphtheria was once quite common, but has now largely been eradicated in developed nations (in the United States for instance, there have been fewer than 5 cases a year reported since 1980, as the DPT (Diphtheria-Tetanus-Pertussis) vaccine is given to all school children). Boosters of the vaccine are recommended for adults because the benefits of the vaccine decrease with age; they are particularly recommended for those travelling to areas where the disease has not been eradicated yet.

Signs and symptoms

The respiratory form has an incubation time of 1-4 days. Symptoms include fatigue, fever, a mild sore throat and problems swallowing. Children infected have symptoms that include nausea, vomiting, chills, and a high fever, although some do not show symptoms until the infection has progressed further. Low blood pressure may develop in some patients. Longer-term effects include cardiomyopathy and peripheral neuropathy (sensory type)[http://www.neuro.wustl.edu/neuromuscular/nother/toxic.htm#diphtheria].

Diagnosis

Laboratory criteria

- Isolation of Corynebacterium diphtheriae from a clinical specimen, or
- Histopathologic diagnosis of diphtheria

Case classification

- Probable: a clinically compatible case that is not laboratory confirmed and is not epidemiologically linked to a laboratory-confirmed case
- Confirmed: a clinically compatible case that is either laboratory confirmed or epidemiologically linked to a laboratory-confirmed case Empirical treatment should generally be started in a patient in whom suspicion of diphtheria is high.

Treatment

The disease may remain manageable, but in more severe cases lymph nodes in the neck may swell, and breathing and swallowing will be more difficult. People in this stage should seek immediate medical attention, as obstruction in the throat may require a tracheotomy. In addition, an increase in heart rate may cause cardiac arrest. Diphtheria can also cause paralysis in the eye, neck, throat, or respiratory muscles. Patients with severe cases will be put in ICUs (Intensive Care Units) at hospitals and be given a diphtheria anti-toxin and bactericidal drugs such as penicillin and erythromycin. Bed rest is important and physical activity should be limited, especially in cases where there is inflammation of the heart muscles. Recovery is generally slow.

Epidemiology

Diphtheria remains a serious disease, with 5-10% percent fatality and up to 20% in children younger than 5 or adults older than 40. Outbreaks, though very rare, still can occur worldwide, even in developed nations. After the breakup of the old Soviet Union in the late 1980s, vaccination rates fell so low that there was an explosion of diphtheria cases. In 1991 there were 2,000 cases of diphtheria in Russia and its newer independent states. By 1998 there were as many as 200,000 cases, with 5,000 deaths, according to Red Cross estimates. This was so great an increase that it was cited in the Guinness Book of World Records as "most resurgent disease". Such statistics show that constant vigilance must be maintained even on largely eradicated diseases, especially since many of these diseases show growing resistance to drugs that have been used to fight them for decades. From the CDC guidelines: :Cutaneous diphtheria should not be reported. Respiratory disease caused by nontoxigenic C. diphtheriae should be reported as diphtheria. All diphtheria isolates, regardless of association with disease, should be sent to the Diphtheria Laboratory, National Center for Infectious Diseases, CDC.

History

Diphtheria (dif-thir-ee-uh or often dip-thir-ee-uh) takes its name from the Greek word for "leather", dipthera, and was named in 1855 by French physician Armand Trousseau (1801-1867). This coinage alludes to the leathery, sheath-like membrane that grows on the tonsils, throat and in the nose. Diphtheria was once one of the most dreaded diseases, with frequent large-scale outbreaks. From 1735-1740, a diphtheria epidemic in the New England colonies was said to have killed as much as 80% of the children under 10 years of age in some towns. In 1920s there were an estimated 100,000 to 200,000 cases a year of diphtheria in the United States, with 13,000 to 15,000 deaths. Children represented the large majority of cases and fatalities. Armand Trousseau One of the first early effective treatments was discovered in the 1880s by U.S. physician Joseph O'Dwyer (1841-1898). O'Dwyer developed tubes that could be inserted into the throat to prevent victims from suffocating from the membrane sheath that grew and obstructed the airways. In the 1890s, the German physician Emil von Behring developed an anti-toxin that, although it did not kill the bacteria, neutralized the toxic poisons that the bacteria released into the body. For this (and his serum therapy for diphtheria), he won the first Nobel Prize in Medicine. (Americans William H. Park and Anna Wessels Williams also developed a diphtheria antitoxin in the 1890s.) Effective vaccines were not developed until the discovery and development of sulfa drugs following World War II. Diphtheria was also prevalent in the British royal family during the late 19th century. Famous cases included a daughter and granddaughter of Britain's Queen Victoria. Princess Alice of Hesse (second daughter of Queen Victoria) died of diphtheria after she contracted it from her children in December of 1878 while nursing them. One of Princess Alice's own daughter, Princess Marie also died of diphtheria in November of 1878 when she was only four years old.

Source

- The first version of this article was adapted from the CDC document "Diphtheria - 1995 Case Definition" at http://www.cdc.gov/epo/dphsi/casedef/diphtheria_current.htm. As a work of an agency of the U.S. Government without any other copyright notice it should be available as a public domain resource. Category:Infectious diseases ms:Difteria ja:ジフテリア

Respiration (physiology)

Respiration is the process of exchanging oxygen and carbon dioxide between an organism and its external environment (breathing). See also: human respiratory system. There are several ways to dichotomize the physiology of respiration:

By species

- Aquatic respiration
- Buccal pumping

By mechanism

- Gas exchange
- Arterial blood gas
- Control of respiration
- Apnea

By experiments

- Huff and puff apparatus
- Respirometer
- SIFT-MS selected ion flow tube mass spectrometry
- Bell jar model lung

By disorders and emergencies

- Sudden Infant Death Syndrome
- Myasthenia gravis
- Asthma
- Drowning
- Choking
- Dyspnea
- Anaphylaxis
- Pneumonia
- Severe acute respiratory syndrome
- Aspiration (medicine) - Pulmonary edema

By medication

- Bronchodilator
- Asthma medication

By intensive care and emergency medicine

- CPR
- Mechanical ventilation
- Intubation
- Iron lung
- Intensive care medicine
- Liquid breathing
- ECMO
- Oxygen toxicity
- Medical ventilator
- Paramedic
- Life support
- General anaesthesia
- Bronchoscopy
- Laryngoscope

By other medical topics

- Respiratory therapy
- Breathing gases
- Hyperbaric oxygen therapy
- Hypoxia
- Gas embolism
- Decompression sickness
- Barotrauma
- Oxygen toxicity
- Nitrogen narcosis
- Carbon dioxide poisoning
- Carbon monoxide poisoning
- HPNS
- Salt water aspiration syndrome

Tonsil

The tonsils are areas of lymphoid tissue on either side of the throat. An infection of the tonsils is called tonsillitis. As with other organs of the lymphatic system, the tonsils act as part of the immune system to help protect against infection. In particular, they are believed to be involved in helping fight off pharyngeal and upper respiratory tract infections. Tonsils in humans include, from superior to inferior: pharyngeal tonsils (also known as adenoids), tubal tonsils, palatine tonsils, and lingual tonsils. Together this set of lymphatic tissue is called the tonsillar ring or Waldeyer's ring. Tonsils tend to reach their largest size near puberty, and they gradually undergo atrophy thereafter. However, they are largest relative to the diameter of the throat in young children, and tonsillectomy may be indicated if they are obstructing the airway or interfering with swallowing. Most commonly, the term "tonsils" refers to the palatine tonsils that can be seen in the back of the throat. Tonsillitis is an inflammation the tonsils and will often, but not necessarily, cause a sore throat and fever. Category:Head and neck

Corynebacterium diphtheriae

Corynebacterium diphtheriae is a pathogenic bacterium that causes diphtheria. It is also known as the Klebs-Löffler bacillus, because it was discovered in 1884 by German bacteriologists Edwin Klebs (1834 – 1912) and Friedrich Löffler (1852 – 1915). C. diphtheriae is an aerobic Gram positive organism, characterized by non-encapsulated, non-sporulated, immobile, straight or curved rods with a length of 1 to 8 µm and width of 0.3 to 0.8 µm, which form ramified aggregations in culture (looking like "Chinese characters"). It is not pathogenic only in humans. Many strains of C. diphtheriae produce a proteic exotoxin with a molecular weight of 62 kilodaltons, which is responsible for the signs of diphtheria. The inactivation of this toxin with an antitoxic serum (antitoxin) is the basis of the antidiphtheric vaccination. However, not all strains are toxigenic; toxin production is associated with infection of the bacterium by a bacteriophage. Three subspecies are recognized: C. diphtheriae mitis, C. diphtheriae intermedius, and C. diphtheriae gravis. The three subspecies differ slightly in their ability to metabolize certain nutrients, but all may be toxigenic (and therefore cause diphtheria) or non-toxigenic. The bacterium is sensitive to the majority of antibiotics, such as the penicillins, ampicillin, cephalosporins, quinolones, chloramphenicol, tetracyclines, cefuroxime and trimethoprim. Category:Actinobacteria Category:Bacteriology

Gram-positive

Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to Gram-negative bacteria, which are not affected by the stain. The stain is caused by a high amount of peptidoglycan in the cell wall, which typically, but not always lacks the secondary membrane and lipopolysaccharide layer found in Gram-negative bacteria. In the original bacterial phyla, the gram-positive forms made up the phylum Firmicutes, a name now used for the largest group. It includes many well-known genera such as Bacillus, Listeria, Staphylococcus, Streptococcus, Enterococcus, and Clostridium. It has also been expanded to include the Mollicutes, bacteria like Mycoplasma that lack cell walls and so cannot be stained by Gram, but are derived from such forms. The actinobacteria are another major group of gram-positive bacteria; they and the Firmicutes are referred to as the high and low G+C groups based on the guanosine and cytosine content of their DNA. If the second membrane is a derived condition, the two may have been basal among the bacteria, otherwise they are probably a relatively recent monophyletic group. They have been considered as possible ancestors for the archaeans and eukaryotes, both because they are unusual in lacking the second membrane and because of various biochemical similarities such as the presence of sterols. The Deinococcus-Thermus group of bacteria also have gram-positive stains, although they are structurally similar to gram-negative bacteria. Both gram-positive and gram-negative bacteria may have a membrane called an S-layer. In gram-negative bacteria, the S-layer is directly attached to the outer membrane. In gram-positive bacteria, the S-layer is attached to the peptidoglycan layer. Category:Bacteria

Bacterium

Actinobacteria
Aquificae
Bacteroidetes/Chlorobi
Chlamydiae/Verrucomicrobia
Chloroflexi
Chrysiogenetes
Cyanobacteria
Deferribacteres
Deinococcus-Thermus
Dictyoglomi
Fibrobacteres/Acidobacteria
Firmicutes
Fusobacteria
Gemmatimonadetes
Nitrospirae
Planctomycetes
Proteobacteria
Spirochaetes
Thermodesulfobacteria
Thermomicrobia
Thermotogae Bacteria (singular: bacterium) are a major group of living organisms. Most are microscopic and unicellular, with a relatively simple cell structure lacking a cell nucleus, and organelles such as mitochondria and chloroplasts. Their cell structure is further described in the article about prokaryotes, because bacteria are prokaryotes, in contrast to organisms with more complex cells, called eukaryotes. The term "bacteria" has variously applied to all prokaryotes or to a major group of them, otherwise called the eubacteria, depending on ideas about their relationships. In Wikipedia, bacteria is used specifically to refer to the eubacteria. Bacteria are the most abundant of all organisms. They are ubiquitous in soil, water, and as symbionts of other organisms. Many pathogens are bacteria. Most are minute, usually only 0.5-5.0 μm in their longest dimension, although giant bacteria like Thiomargarita namibiensis and Epulopiscium fishelsoni may grow past 0.5 mm in size. They generally have cell walls, like plant and fungal cells, but with a very different composition (peptidoglycans). Many move around using flagella, which are different in structure from the flagella of other groups.

History and taxonomy

The first bacteria were observed by Antony van Leeuwenhoek in 1683 using a single-lens microscope of his own design. The name bacterium was introduced much later, by Ehrenberg in 1828, derived from the Greek word βακτηριον meaning "small stick". Louis Pasteur (1822-1895) and Robert Koch (1843-1910) described the role of bacteria as conveyors and causes of disease or pathogens.

Metabolism

Bacteria show a wide variety of different metabolisms and can accordingly be classified into primary nutritional groups. The most common division is between heterotrophs, which depend on an organic source of carbon, and autotrophs, which are able to synthesize organic compounds from carbon dioxide and water. Autotrophs that obtain energy by oxidizing chemical compounds are called chemotrophs, and those that obtain their energy from light, via photosynthesis, are called phototrophs. There are many variations on this terminology such as chemoautotrophs and photosynthetic autotrophs and so on. In addition, bacteria are distinguished based on the source of reducing equivalents they are using. Those using inorganic compounds (e. g. water, hydrogen, sulfide or ammonia) for this purpose are called lithotrophs and others needing organic compounds (e. g. sugars or organic acids) and are called organotrophs. The metabolic modes of energy metabolism (phototrophy or chemotrophy), reducing equivalent sources (lithotrophy or organotrophy) and carbon sources (autotrophy or heterotrophy) can be combined differently in any single microorganism, and even shifting between different modes frequently occurs in many species. Other nutritional requirements include nitrogen, sulfur, phosphorus, vitamins and metallic elements such as sodium, potassium, calcium, magnesium, manganese, iron, zinc, cobalt, copper and nickel for normal growth. For some species, additional trace elements such as selenium, tungsten, vanadium or boron are needed. Based on their response to oxygen, most bacteria can be placed into one of three groups: Some bacteria can grow only in the presence of oxygen and are called aerobes; others can grow only in the absence of oxygen and are called anaerobes; and some can grow in the presence or absence of oxygen and are called facultative anaerobes.

Movement

Motile bacteria can move about, either using flagella, bacterial gliding, or changes of buoyancy. A unique group of bacteria, the spirochaetes, have structures similar to flagella, called axial filaments, between two membranes in the periplasmic space. They have a distinctive helical body that twists about as it moves. Bacterial flagella are arranged in many different ways. Bacteria can have a single polar flagellum at one end of a cell, clusters of many flagella at one end or flagella scattered all over the cell, as with Peritrichous. Many bacteria (such as E.coli) have two distinct modes of movement: forward movement (swimming) and tumbling. The tumbling allows them to reorient and introduces an important element of randomness in their forward movement. (see external links below for link to videos). Motile bacteria are attracted or repelled by certain stimuli, behaviors called taxes - for instance, chemotaxis, phototaxis, mechanotaxis and magnetotaxis. In one peculiar group, the myxobacteria, individual bacteria attract to form swarms and may differentiate to form fruiting bodies. The myxobacteria move only when on solid surfaces, unlike E. coli which is motile in liquid or solid media.

Groups and identification

myxobacteria Bacteria come in a variety of different shapes. Most are rod-shaped, sphere-shaped, or helix-shaped; these are respectively referred to as bacilli, cocci, and spirilla. An additional group, vibrios, are comma-shaped. Shape is no longer considered a defining factor in the classification of bacteria, but many genera are named for their shape (e.g. Bacillus, Streptococcus, Staphylococcus) and it is an important part in their identification. Another important tool is Gram staining, named after Hans Christian Gram who developed the technique. This separates bacteria into two groups, based on the composition of their cell wall. The first formal grouping of bacteria into phyla was based largely on this test:
- Gracilicutes - bacteria with a second cell membrane containing lipids, giving them Gram-negative stains
- Firmicutes - bacteria with a single membrane and thick peptidoglycan wall, giving them Gram-positive stains
- Mollicutes - bacteria with no second membrane or wall, giving them Gram-negative stains The archeabacteria were originally included as the Mendosicutes. As given, these phyla are no longer believed to represent monophyletic groups. The Gracilicutes have been divided into many different phyla. Most gram-positive bacteria are placed in the phyla Firmicutes and Actinobacteria, which are closely related. However, the Firmicutes have been redefined to include the mycoplasmas (Mollicutes) and certain Gram-negative bacteria.

Benefits and dangers

Bacteria are both harmful and useful to the environment, and animals, including humans. The role of bacteria in disease and infection is important. Some bacteria act as pathogens and cause tetanus, typhoid fever, pneumonia, syphilis, cholera, foodborne illness and tuberculosis. Sepsis, a systemic infectious syndrome characterized by shock and massive vasodilation, or localized infection, can be caused by bacteria such as streptococcus, staphylococcus, or many gram-negative bacteria. Some bacterial infections can spread throughout the host's body and become systemic. In plants, bacteria cause leaf spot, fireblight, and wilts. The mode of infection includes contact, air, food, water, and insect-borne microorganisms. The hosts infected with the pathogens may be treated with antibiotics, which can be classified as bacteriocidal and bacteriostatic, which at concentrations that can be reached in bodily fluids either kill bacteria or hamper their growth, respectively. Antiseptic measures may be taken to prevent infection by bacteria, for example, prior to cutting the skin during surgery or swabbing skin with alcohol when piercing the skin with the needle of a syringe. Sterilization of surgical and dental instruments is done to make them sterile or pathogen-free to prevent contamination and infection by bacteria. Sanitizers and disinfectants are used to kill bacteria or other pathogens to prevent contamination and risk of infection. In soil, microorganisms help in the transformation of nitrogen to ammonia with enzymes secreted by these microbes, which reside in the rhizosphere (a zone that includes the root surface and the soil that adheres to the root after gentle shaking). Some bacteria are able to use molecular nitrogen as their source of nitrogen, converting it to nitrogenous compounds, a process known as nitrogen fixation. Many other bacteria are found as symbionts in humans and other organisms. For example, the presence of the gut flora in the large intestine can help prevent the growth of potentially harmful microbes. The ability of bacteria to degrade a variety of organic compounds is remarkable. Highly specialized groups of microorganisms play important roles in the mineralization of specific classes of organic compounds. For example, the decomposition of cellulose, which is one of the most abundant constituents of plant tissues, is mainly brought about by aerobic bacteria that belong to the genus Cytophaga. This ability has also been utilized by humans in industry, waste processing, and bioremediation. Bacteria capable of digesting the hydrocarbons in petroleum are often used to clean up oil spills. Some beaches in Prince William Sound were fertilized in an attempt to facilitate the growth of such bacteria after the infamous 1989 Exxon Valdez oil spill. These efforts were effective on beaches that were not too thickly covered in oil. Bacteria, often in combination with yeasts and molds, are used in the preparation of fermented foods such as cheese, pickles, soy sauce, sauerkraut, vinegar, wine, and yogurt. Using biotechnology techniques, bacteria can be bioengineered for the production of therapeutic drugs, such as insulin, or for the bioremediation of toxic wastes.

Miscellaneous

Two organelles, mitochondria and chloroplasts, are generally believed to have been derived from endosymbiotic bacteria. Microorganisms are widely distributed and are most abundant where they have food, moisture, and the right temperature for their multiplication and growth. They can be carried by air currents from one place to another. The human body is home to billions of microorganisms; they can be found on skin surfaces, in the intestinal tract, in the mouth, nose, and other body openings. They are in the air one breathes, the water one drinks, and the food one eats. The great antiquity of the bacteria has enabled them to evolve a great deal of genetic diversity. They are far more diverse than, say, the mammals or insects. For instance, the genetic distance between E. coli and Thermus aquaticus is greater than the distance between humans and oak trees.

References

- Some text in this entry was merged with the Nupedia article entitled Bacteria, written by Nagina Parmar; reviewed and approved by the Biology group (editor: Gaytha Langlois, lead reviewer: Gaytha Langlois, lead copyeditors: Ruth Ifcher and Jan Hogle)
-

External links

- [http://www.dsmz.de/bactnom/bactname.htm Bacterial Nomenclature Up-To-Date from DSMZ]
- [http://www.sciencenews.org/pages/sn_arc99/4_17_99/fob5.htm The largest bacteria]
- [http://tolweb.org/tree?group=Eubacteria&contgroup=Life_on_Earth Tree of Life]
- [http://www.rowland.harvard.edu/labs/bacteria/index_movies.html Videos] of bacteria swimming and tumbling, use of optical tweezers and other fine videos.
- Category:Bacteriology ko:세균 ja:真正細菌 th:แบคทีเรีย

DPT vaccine

DPT is a vaccine designed to immunize against diphtheria, pertussis, and tetanus. Diphtheria is a very serious bacterial disease that can make a person unable to breathe, cause paralysis, or even heart failure. Before the DPT shot was introduced, 17,000 children died in a single year in the United States in a diphtheria epidemic. Moderate reactions to the DPT vaccine occur in 0.1% to 1.0% of children and include ongoing crying (for three hours or more), a high fever (up to 105 degrees F), and an unusual, high-pitched crying. Severe problems from the DPT immunization happen very rarely. These include a serious allergic reaction, a prolonged seizure, a decrease in consciousness, lasting brain disease, or even death. These severe neurologic events occur after approximately 1 in 140,000 doses of the DPT vaccine (0.0007%). Most of the reactions to DPT injection are thought to be from the pertussis component. The term DTP vaccine is also frequently used. The terms "DTwP" and "DTaP" are sometimes used, with "wP" referring to "whole cell pertussis" and "aP" referring to "acellular pertussis". (The acellular form is considered safer.)

External links

- [http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202201.html NIH/Medline 1]
- [http://www.nlm.nih.gov/medlineplus/ency/article/002021.htm NIH/Medline 2]
- [http://www.emedicinehealth.com/articles/11995-3.asp eMedicine]
- [http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Diphtheria_tetanus_pertussis_for_children?OpenDocument BetterHealth (Australian)]
- PMID 16330737
- PMID 16299307 Category:Vaccines

Tetanus

Tetanus is a serious and often fatal disease caused by the neurotoxin tetanospasmin which is produced by the Gram-positive, obligate anaerobic bacterium Clostridium tetani. Tetanus also refers to a state of muscle tension. It was first documented by Hippocrates, and records dating back to the 5th century BCE provide countless clinical observations of the disease. However, the etiology of the disease was not discovered until 1884 by Carle and Rattone. Passive tetanus immunisation was first implemented during World War I. Bacilli of C. tetani can be found in soil (especially agricultural soil), and the intestines and feces of horses, sheep, cattle, rats, dogs, cats, guinea pigs, and chickens. Spores are found in manure-treated soil, skin surfaces (of both animals and humans), under nail-beds, and in contaminated heroin. There are four different clinical forms of tetanus: local (uncommon), cephalic (rare), generalized (most common), and neonatal (a common cause of infant mortality in underdeveloped countries). Generalized tetanus accounts for 80% of tetanus cases.

Symptoms

The incubation period for tetanus is 3 to 21 days (with the average being about 8 days). For neonates, the incubation period is 4 to 14 days, with 7 days being the average. Most of the time, the further the wound is from the central nervous system, the longer the incubation period. Incubation period length and likelihood of death are inversely proportional. The first sign of tetanus is lockjaw (trismus), followed by stiffness of the neck and back, risus sardonicus, difficulty swallowing, and muscle rigidity in the abdomen. The stiffness and spasming of muscles expands throughout the body inferiorly. Typical signs of tetanus include an increase in body temperature by 2 to 4 °C, diaphoresis (excessive sweating), an elevated blood pressure, and an episodic rapid heart rate. Spasms and muscle contraction last for 3 to 4 weeks, and complete recovery may take months. About 30% of tetanus victims die, most of whom are elderly patients. In developing countries, the mortality rate may be as high as sixty percent. Complications of the disease include spasms of the larynx (vocal cords), accessory muscles (chest muscles used to aid in breathing), and the diaphragm (the primary breathing muscle); fractures of long bones secondary to violent muscle spasms; and hyperactivity of the autonomic nervous system.

Treatment

The wound must be cleaned. Penicillin and metronidazole will help decrease the amount of bacteria but they have no effect on the toxin produced by the bacteria. Human anti-tetanospasmin immunoglobulin should be given. Diazepam and DTaP vaccine booster are also given. Tetanus can be prevented by vaccination. A booster vaccine is recommended every ten years, and standard care in many places is to give the booster to any patient with a puncture wound who is uncertain of when he or she was last vaccinated. There was a shortage of tetanus vaccine in the United States in 2001 and 2002, but this supply issue was corrected in 2003. There are, on average, around 150 cases annually in the USA.

Association with rust

Tetanus is often associated with rust, especially rusty nails, but this is somewhat misleading. Rust itself does not cause tetanus or contain more C. tetani bacteria. Objects that accumulate rust are often found in the outdoors or places that generally contain more bacteria. Since C. tetani is an anaerobic bacterium, it will thrive in an environment that lacks oxygen. Therefore, stepping on an old forgotten nail in a stable could easily result in tetanus, partly because C. tetani is found in animal feces (which is rather abundant in a stable) and the puncture wound would effectively create an ideal breeding ground for the bacteria (because of the lack of oxygen). Such an old nail would likely be rusty, but a lack of rust would provide no protection. On the other hand, someone scratching themselves against a rusty fire escape ladder in an urban setting would have a much lesser chance of getting tetanus since fire escape ladders do not often come into intimate contact with soil, dirt or organic waste and the wound itself (a scratch) does not create an oxygen-poor environment. See also: Correlation implies causation (logical fallacy)

Around the globe

Tetanus is a global health problem since Clostridium tetani spores are ubiquitous. The disease occurs almost exclusively in persons who are unvaccinated or inadequately immunized. Tetanus occurs worldwide but is more common in hot, damp climates with soil rich in organic matter. Tetanus, particularly the neonatal form, remains a significant public health problem in non-industrialized countries, causing an estimated 400,000 deaths each year. Category:Infectious diseases ms:Kancing gigi ja:破傷風

Pertussis

Pertussis, also known as whooping cough, is a highly contagious disease that is one of the leading causes of vaccine-preventable deaths. There are 30–50 million cases per year, and about 300,000 deaths per year. Virtually all deaths occur in children under one year of age. Ninety percent of all cases occur in developing countries. It is caused by certain species of the bacterium Bordetella—usually B. pertussis, but some cases are caused by B. parapertussis. The disease was recognizably described as early as 1578, and B. pertussis was isolated in pure culture in 1906 by Jules Bordet and Octave Gengou. The complete B. pertussis genome of 4,086,186 base pairs was sequenced in 2002.

Characterization

The disease is characterized initially by mild respiratory infection symptoms such as cough, sneezing, and runny nose. After one to two weeks the cough changes character, with paroxysms of coughing followed by an inspiratory "whooping" sound. Coughing fits may be followed by vomiting, which in severe cases leads to malnutrition. Coughing fits gradually diminish over one to two months. Other complications of the disease include pneumonia, encephalitis, pulmonary hypertension, and secondary bacterial superinfection.

Transmission

The disease is spread by contact with airborne discharges from the mucous membranes of infected people. Laboratory diagnosis include; Calcium alginate throat swab, culture on Bordet-Gengou medium, immunofluorescence and serological methods. Treatment of the disease with antibiotics (often erythromycin, azithromycin, clarithromycin or trimethoprim-sulfamethoxazole) results in the person becoming less infectious but probably does not significantly alter the outcome of the disease. Close contacts who receive appropriate antibiotics, "chemoprophylaxis", during the 7–21 day incubation period may be protected from developing symptomatic disease.

Vaccines

Pertussis vaccines were initially formulated in 1926—most notable by [http://www.enh.org/researchandacademics/research/aboutus/index.asp?id=333 Dr. Louis W. Sauer] of Northwestern University and [http://www.enh.org Evanston Hospital]—as whole-cell preparations, but are now available as acellular preparations, which cause fewer side effects. They offer protection for only a few years, and are given so that immunity lasts through childhood, the time of greatest exposure and greatest risk. The immunizations are often given in combination with tetanus and diphtheria immunizations, at ages 2, 4, and 6 months, and later at 15–18 months and 4–6 years. Traditionally, pertussis vaccines are not given after age seven, as the frequency of side effects associated with the immunization increased with age. The most serious side-effects of immunization are neurological: they include seizures and hypotonic episodes. An acellular vaccine preparation for older individuals is available in Canada and Europe, and two such products are being evaluated for their safety in adolescents and adults in the United States; a Food and Drug Administration decision is expected in 2005.

Other notes

The disease is much milder in adults than in children and many cases go undiagnosed. This disease is one of several that ravaged Native American populations after Europeans colonized the New World. Bordetella pertussis elaborates several virulence factors, including: pertussis toxin, an adenylate cyclase toxin, filamentous hemagglutinin, a tracheal cytotoxin, fimbriae, and pertactin. Category:Infectious diseases ja:百日咳 ms:Batuk kokol

Vaccine

A vaccine is an antigenic preparation used to produce active immunity to a disease, in order to prevent or ameliorate the effects of infection by any natural or 'wild' strain of the organism. The term derives from vaccinia, the infectious viral agent of cowpox ("vacca" means cow in Spanish), which, when administered to humans, provided them protection against smallpox. The process of distributing and administrating vaccines is referred to as vaccination.

Origin of vaccines

Smallpox was the first disease people tried to prevent by purposely inoculating themselves with other types of infections. Inoculation is believed to have started in India or China before 200 BC. Physicians in China immunized patients by picking off pieces from drying pustules of a person suffering from a mild case of smallpox, grinding the scales to a powdery substance, and then inserting the powder into the person's nose in order for them to be immunized. In 1718, Lady Mary Wortley Montague reported that the Turks have a habit of deliberately inoculating themselves with fluid taken from mild cases of smallpox. Lady Montague inoculates her own children in this manner. In 1796, during the heyday of the smallpox virus in Europe, an English country doctor, Edward Jenner, observed that milkmaids would sometimes become infected with cowpox through their interactions with dairy cows' udders. Cowpox is a mild relative of the deadly smallpox virus. Building on the foundational practice of inoculation, Jenner took infectious fluid from the hand of milkmaid Sarah Nelmes. He inserted this fluid, by scratching or injection, into the arm of a healthy local eight year old boy, James Phipps. Phipps then showed symptoms of cowpox infection. Forty-eight days later, after Phipps had fully recovered from cowpox, Jenner injected smallpox-infected matter into Phipps, but Phipps did not later show signs of smallpox infection.

Types of vaccines

Vaccines may be living, weakened strains of viruses or bacteria which intentionally give rise to inapparent-to-trivial infections. Vaccines may also be killed or inactivated organisms or purified products derived from them. There are three types of traditional vaccines[http://www.immunecentral.com/infotemplate.cfm-1702-72-1]:
- Inactivated - these are previously virulent micro-organisms that have been killed with chemicals or heat. Examples are vaccines against flu, cholera, plague, and hepatitis A. Most such vaccines may have incomplete or short-lived immune responses and are likely to require booster shots.
- Live, attenuated - these are live micro-organisms that have been cultivated under conditions to disable their virulent properties. They typically provoke more durable immunological responses and are the prefered type for healthy adults. Examples include yellow fever, measles, rubella, and mumps.
- Toxoids - these are inactivated toxic compounds from micro-organisms in cases where these (rather than the micro-organism itself) causes illness. Examples of toxoid-based vaccines include tetanus and diphtheria The live tuberculosis vaccine is not the contagious TB strain, but a related strain called "BCG"; it is used in the United States very infrequently. A number of innovative vaccines are also in development and also in use:
- Conjugate - certain bacteria have polysaccharide outer coats that are poorly immunogenic. By linking these outer coats to proteins (e.g. toxins), the immune system can be led to recognize the polysaccharide as if it were a protein antigen.
- Subunit - rather than introducing a whole inactivated or attenuated micro-organism to an immune system, a fragment of it can create an immune response
- Recombinant Vector - by combining the physiology of one micro-organism and the DNA of the other, immunity can be created against diseases that have complex infection processes
- DNA vaccination - in recent years a new type of vaccine, created from an infectious agent's DNA called DNA vaccination, has been developed. It works by insertion (and expression, triggering immune system recognition) into human or animal cells, of viral or bacterial DNA. These cells then develop immunity against an infectious agent, without the effects other parts of a weakened agent's DNA might have. As of 2005, DNA vaccination is still experimental, but shows some promising results.

Developing immunity

The immune system recognizes vaccine agents as foreign, destroys them, and 'remembers' them. When the virulent version of an agent comes along, the immune system is thus prepared to respond, by (1) neutralizing the target agent before it can enter cells, and (2) by recognizing and destroying infected cells before that agent can multiply to vast numbers. Vaccines have contributed to the eradication of smallpox, one of the most contagious and deadly diseases known to man. Other diseases such as rubella, polio, measles, mumps, chickenpox, and typhoid are nowhere near as common as they were just a hundred years ago. As long as the vast majority of people are vaccinated it is much more difficult for an outbreak of disease to occur, let alone spread. This effect is called herd immunity.

Controversy surrounding the use of vaccines

See article: Vaccine controversy Opposition to vaccination, from a wide array of vaccine critics, has existed since the earliest vaccination campaigns: [http://bmj.bmjjournals.com/cgi/reprint/325/7361/430?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&andorexacttitle=and&andorexacttitleabs=and&fulltext=anti-vaccinationists&andorexactfulltext=and&searchid=1113046719196_3655&stored_search=&FIRSTINDEX=0&sortspec=relevance&resourcetype=1,2,3,4]. A number of vaccines, including those given to very young children, have contained thimerosal, a preservative that metabolizes into ethylmercury. It has been used in some influenza, DTP (diphtheria, tetanus and pertussis) vaccine formulations. Since 1997, use of thimerosal has been gradually diminishing in western industrialized countries after recommendations by medical authorities, but trace amounts of thimerosal remain in many vaccines and in some vaccines, thimerosal has not yet been phased out despite recommendations. Some states in USA have accepted laws banning the use of thimerosal in childhood vaccines. In the late 1990s, controversy over vaccines escalated in both the US and the United Kingdom when a study, published in the respected journal Lancet, by Dr. Andrew Wakefield suggested a possible link between bowel disorders, autism and MMR vaccine, and urged further research [http://briandeer.com/mmr/lancet-paper.htm]. His report garnered significant media attention, leading to a drop in the uptake of the MMR vaccine in the UK and some other countries. The study garnered criticism for its small sample size, and for failing to use healthy controls. In response to the controversies, a number of studies with larger sample sizes were conducted, and failed to confirm the findings.[http://bmj.bmjjournals.com/cgi/reprint/325/7361/419?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&andorexacttitle=and&andorexacttitleabs=and&fulltext=vaccines+history+&andorexactfulltext=and&searchid=1113045633124_3161&stored_search=&FIRSTINDEX=0&sortspec=relevance&resourcetype=1,2,3,4] [http://bmj.bmjjournals.com/cgi/reprint/324/7334/393?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=1&author1=taylor%2C+b&author2=miller%2C+e&andorexacttitle=and&andorexacttitleabs=and&andorexactfulltext=and&searchid=1113249908936_21240&stored_search=&FIRSTINDEX=0&sortspec=relevance&resourcetype=1,2,3,4]. In 2004, 10 of the 13 authors of the original Wakefield study retracted the paper's interpretation, without disputing the central finding of a consistent set of bowel disorders among the autistic study subjects, stating the data were insufficient to establish a causal link between MMR vaccine and autism.[http://briandeer.com/mmr/lancet-retraction.htm] In 2004 and 2005, England and Wales have seen an increase in the incidence of mumps infections among adolescents and young adults, which health authorities attribute to a decline in booster shots from 92% to 80%, which they believe is due to the alleged misinformation generated by Wakefield's study [http://www.nzherald.co.nz/index.cfm?c_id=2&ObjectID=10125382]. Also in 2004, the United States' Institute of Medicine reported that evidence "favors rejection" of any link between vaccines containing thimerosal, or MMR, and the development of autism [http://www.iom.edu/report.asp?id=20155].

Potential for adverse side effects in general

Some refuse to immunize themselves or their children, because they believe certain vaccines' adverse side effects outweigh their benefits. A variation of this reasoning is that not enough is known of the adverse effects to determine whether the potential benefits make the risks worthwhile. Since most people are vaccinated against contagious and potentially fatal diseases, the chances of someone who is not vaccinated becoming ill is a good deal smaller than it might be if their opinion was held by more people. Thus they acquire some of the benefits of vaccines, through herd immunity, without assuming the risks those who choose to vaccinate do. Advocates of recommended routine vaccination argue that side effects of most approved vaccines are either far less serious than actually catching the disease, or are very rare, and argue that the calculus of risk/benefit ratio should be based on benefit to humanity rather than simply on the benefit to the immunized individual. The main risk of rubella, for example, is to the fetuses of pregnant women, but this risk can be effectively reduced by the immunization of children to prevent transmission to pregnant women.

Efficacy of vaccines

It's worthwhile to note that vaccines don't guarantee protection from a disease. That is, even having been vaccinated, there is still a remote possibility that a vaccinated person may get the disease. The efficacy or performance of the vaccine is dependent on a number of factors:
- the disease itself (for some diseases vaccination performs better than for other diseases)
- the strain of vaccine (some vaccinations are for different strains of the disease) [http://bmj.bmjjournals.com/cgi/content/full/319/7206/352]
- whether one kept to the timetable for the vaccinations
- some individuals are "non-responders" to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly
- other factors such as ethnicity or genetic predisposition (possibly) In cases where a vaccinated individual does develop the disease vaccinated against, the disease will most likely be milder than if the individual had not been vaccinated.

Economics of vaccine development

One challenge in vaccine development is economic: many of the diseases most demanding a vaccine, including HIV, malaria and tuberculosis, exist principally in poor countries. Pharmaceutical firms and biotech companies have little incentive to develop vaccines for these diseases because there is so little revenue potential. Most vaccine development to date has relied on "push" funding by government and non-profit organizations, of government agencies, universities and non-profit organizations. To date, there has been very little involvement of private industry on a commercial basis. Many researchers and policymakers are calling for a different approach, using "pull" mechanisms to motivate industry. Mechanisms such as prizes, tax credits, or advance market commitments could ensure a financial return to firms that successfully developed an HIV vaccine. If the policy were well-designed, it might also ensure that people have access to a vaccine if and when it is developed.

Preservatives

In order to extend shelf life and reduce production and storage costs, thimerosal was used routinely until recent years as a preservative. TCVs are gradually being phased out, but may be used in stages of manufacture.

References

- [http://pediatrics.aappublications.org/cgi/content/full/112/3/604 AAPPublications.org] - 'Thimerosal and the Occurrence of Autism: Negative Ecological Evidence From Danish Population-Based Data' Pediatrics, Vol 112, No 3, September 2003 (Denmark study on autism rates)
- [http://bmj.bmjjournals.com/cgi/content/full/319/7206/352 BMJJournals.com] - 'Comparative efficacy of three mumps vaccines', Matthias Schlegel, Joseph J. Osterwalder, Renato L. Galeazzi, Pietro J. Vernazza, British Medical Journal Vol 319, No 352, August 7, 1999
- [http://briandeer.com/mmr/lancet-paper.htm BrianDeer.com] - 'Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children' Andrew Wakefield, et al., The Lancet, Vol 351, No 9103, February 28, 1998
- [http://www.jpands.org/vol8no1/geier.pdf JPandS.org (pdf)] - 'Thimerosal in Childhood Vaccines, Neurodevelopment Disorders, and Heart Disease in the United States', Mark Geier, M.D., Ph.D., and David Geier, B.A., Journal of American Physicians and Surgeons, Vol 8, No 1, Spring, 2003
- [http://www.vaccineinformation.org Vaccine Information.org] - 'Vaccine Information for the Public and Health Professionals'
- [http://americanhistory.si.edu/polio/virusvaccine/history.htm] Vaccine history from smithsonian institute http://www.coldcure.com/html/smallpox.html [article on timeline of vaccine history]
External links

- [http://www.google.co.uk/search?sourceid=navclient&ie=UTF-8&rls=GGLD,GGLD:2005-17,GGLD:en&q=vaccine Google] - 'Google Search about Vaccine'
Vaccine proponent views

- [http://blogs.cgdev.org/vaccine CGDev.org] - Center for Global Development: 'Vaccines for Development' (updated regularly)
- [http://clearlyexplained.com/technology/health/vaccines.html ClearlyExplained.com] - 'Vaccines - ClearlyExplained.com', Richard Conan-Davies, BSc Dip Ed (October 22, 2001)
- [http://www.nlm.nih.gov/medlineplus/immunizationvaccination.html NIH.gov] - 'Immunization' ('conventional' opinion on vaccines), National Institute of Health
- [http://www.townhall.com/columnists/GuestColumns/Fumento20050630.shtml TownHall.com] - 'Don't believe the childhood vaccine fearmongers', Michael Fumento (June 30, 2005)
- [http://www.globalizationandhealth.com/content/1/1/10 Globalization and Health] - Medicines and vaccines for the world's poorest: Is there any prospect for public-private cooperation?
Vaccine safety critical views

- [http://www.imss.macrobiotic.net/vaccinehistory.html MacroBiotic.net] - 'A Short History of Vaccines'
- [http://www.iom.edu/Object.File/Master/19/029/0.pdf IOM.edu (pdf)] - 'Before the Institute of Medicine' (statement on link between thimerosol and autism), US Congressman Dave Weldon, M.D., (February 9, 2004)
- [http://www.novaccine.com NoVaccine.com] - 'The American Vaccine Information Directory' (AVID), Dr. Dan Schultz
- [http://www.truthcampaign.ukf.net/articles/health/vaccination.html TruthCampaign.ukf.net] - 'Vaccination Assault on the Human Species', Pat Rattigan, ND Category:Virology Category:Infectious diseases ko:백신 ja:ワクチン nb:Vaksine th:วัคซีน

Low blood pressure

In physiology and medicine, hypotension refers to an abnormally low blood pressure. It is often associated with shock, though not necessarily indicative of it. Hypotension is not to be confused with hypertension.

Causes

Orthostatic hypotension is a common cause of low blood pressure, resulting from a sudden change in body position. Reduced blood volume, called hypovolæmia, can also cause hypotension and often results from the use of diuretics or vasodilators such as nitric oxide or furosemide. It has been recorded as a side-effect of certain forms of anesthesia, such as curare, in which event it is often treated by the anesthesiologist. Another -- albeit rare -- form, is "post prandial hypotension", which occurs 30-75 minutes after eating. It is not well understood.

Indicators

For most individuals, a healthy blood pressure lies between 90/60 mmHg to 130/80 mmHg. A small drop in blood pressure, even as little as 20 mmHg, can result in transient hypotension.

Symptoms

Low blood pressure is often accompanied by:
- Chest pain
- Shortness of breath
- Irregular heartbeat
- Fever higher than 101 °F (38.3 °C)
- Headache
- Stiff neck
- Severe upper back pain
- Cough with phlegm
- Prolonged diarrhea or vomiting
- Inability to eat or drink
- Burning with urination
- Foul-smelling urine
- Adverse effect of medications
- Acute, life-threatening allergic reaction
- Dizziness, or light-headedness
- Seizures
- Loss of consciousness

References

- [http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Hypovolemia - MedLine Plus]
- [http://my.webmd.com/content/article/54/61510.htm hypotension WebMD]

Peripheral neuropathy

Peripheral neuropathy is the medical term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the side-effects of systemic illness. Peripheral neuropathies vary in their presentation and origin, and may affect the nerve or the neuromuscular junction. Major causes of peripheral neuropathy include seizures, nutritional deficiencies, alcoholism and HIV, though diabetes is the most likely cause. Mechanical pressure from staying in one position for too long, a tumor, intraneural hemorrhage, exposing the body to extreme conditions such as radiation, cold temperatures, or toxic substances can also cause peripheral neuropathy. Many of the diseases of the peripheral nervous system may present similarly to muscle problems (myopathies), and so it is important to develop approaches for assessing sensory and motor disturbances in patients so that a physician may make an accurate diagnosis.

Types

Peripheral neuropathies may either be symmetrical and generalized or focal and multifocal, which is usually a good indicator of the cause of the peripheral nerve disease.

Generalized peripheral neuropathy

Generalized peripheral neuropathies are symmetrical, and usually due to various systematic illnesses and disease processes that affect the peripheral nervous system in its entirety. They are further subdivided into several categories:
- Distal axonopathies are the result of some metabolic or toxic derangement of neurons. They may be caused by metabolic diseases such as diabetes, renal failure, deficiency syndromes such as malnutrition and alcoholism, or the effects of toxins or drugs.
- Myelinopathies are due to a primary attack on myelin causing an acute failure of impulse conduction. The most common cause is acute inflammatory demyelinating polyneuropathy (AIDP; aka Guillain-Barré syndrome), though other causes include chronic inflammatory demyelinating syndrome (CIDP), genetic metabolic disorders (e.g., leukodystrophy), or toxins.
- Neuronopathies are the result of destruction of peripheral nervous system (PNS) neurons. They may be caused by motor neurone diseases, sensory neuronopathies (e.g., Herpes zoster), toxins or autonomic dysfunction. Neurotoxins may cause neuronopathies, such as the chemotherapy agent vincristine.

Signs and symptoms

Those with diseases or dysfunctions of their peripheral nerves can present with problems in any of the normal peripheral nerve functions. In terms of sensory function, there are commonly loss of function (negative) symptoms, which include numbness, tremor, and gait imbalance. Gain of function (positive) symptoms include tingling, pain, itching, crawling, and pins and needles. Motor symptoms include loss of function (negative) symptoms of weakness, tiredness, heaviness, and gait abnormalities; and gain of function (positive) symptoms of cramps, tremor, and fasciculations. There is also pain in the muscles (myalgia), cramps, etc., and there may also be autonomic dysfunction. During physical examination, those with generalized peripheral neuropathies most commonly have distal sensory or motor and sensory loss, though those with a pathology (problem) of the peripheral nerves may be perfectly normal; may show proximal weakness, as in some inflammatory neuropathies like Guillain-Barré syndrome); or may show focal sensory disturbance or weakness, such as in mononeuropathies, radiculopathies and plexopathies. Common disorders of the peripheral nerves include focal entrapment neuropathies (e.g., carpal tunnel syndrome), generalized peripheral neuropathies (e.g., diabetic neuropathy), plexopathies (e.g., brachial neuritis) and radiculopathies (e.g., of cranial nerve VII; Facial nerve).

References

# [http://www.med.uwo.ca/UME/Diane/Year2Postings2004-2005/Trimester%202/CNS/DiseasesOfThePeripheralNervousSystemDrHahn.pdf Diseases of the peripheral system] - These lecture notes were presented to a second year medical school class at the [http://www.uwo.ca University of Western Ontario] on 2 December 2004 by [http://communications.uwo.ca/contact_western/search_results.html?department=CLINICAL%20NEUROLOGICAL%20SCIENCES Dr. Angelika F. Hahn]. # [http://www.med.uwo.ca/UME/Diane/Year2Postings2004-2005/Trimester%202/CNS/NerveMuscleDiseasePowerpointDrMNicolle.ppt Approach to Muscle and nerve problems] - Powerpoint slides from a lecture presented to a second year medical school class at the [http://www.uwo.ca University of Western Ontario] on 2 December 2004 by [http://communications.uwo.ca/contact_western/search_results.html?department=CLINICAL%20NEUROLOGICAL%20SCIENCES Dr. Michael W. Nicolle]. # [http://www.med.uwo.ca/UME/Diane/Year2Postings2004-2005/Trimester%202/CNS/ApproachToMuscleOrNerveDiseaseDrMNicolle.pdf Approach to Muscle and nerve problems] - Lecture notes from a lecture presented to a second year medical school class at the [http://www.uwo.ca University of Western Ontario] on 2 December 2004 by [http://communications.uwo.ca/contact_western/search_results.html?department=CLINICAL%20NEUROLOGICAL%20SCIENCES Dr. Michael W. Nicolle].

Lymph nodes

Lymph nodes are components of the lymphatic system. Clusters of lymph nodes are found in the underarms, groin, neck, chest, and abdomen. Lymph nodes act as filters, with an internal honeycomb of connective tissue filled with lymphocytes that collect and destroy bacteria and viruses. When the body is fighting an infection, these lymphocytes multiply rapidly and produce a characteristic swelling of the lymph nodes. The spleen and tonsils are large lymphoid organs that serve similar functions, though the spleen does not filter lymph but blood. Lymph nodes are bean-shaped and range in size from a few millimeters to about 1-2 cm in their normal state. They may become enlarged due to a tumor or infection. The lymph node is surrounded by a fibrous capsule, and inside the lymph node the fibrous capsule extends to form trabeculae. Thin reticular fibers form a supporting meshwork inside the node. The concave side of the lymph node is called the hilum. The artery and vein attach at the hilum and allow blood to enter and leave the organ, respectively. The parenchyma of the lymph node is divided into an outer cortex and an inner medulla. The cortex is absent at the hilum. The cortex contains several oval-shaped lymphoid nodules (also called follicles) which are aggregates of lymphocytes contained within a meshwork of supporting cells. Nodules that consist mainly of small lymphocytes are called primary nodules. Nodules called secondary nodules are those that contain a pale central region called a germinal center. The germinal center forms (and thus a primary nodule becomes a secondary nodule) when a B cell that has recognized an antigen undergoes proliferation, differentiates into plasma cells, and forms antibodies. The band of the cortex adjacent to the medulla is the deep cortex, also called the juxtamedullary cortex or paracortex. This layer is devoid of nodules. Formation of the deep cortex depends on the migration of T cells. Thus it is sometimes also called the thymus-dependent cortex. In comparison, the layer of the cortex that contains nodules is called the nodular cortex. The medulla consists of cords of lymphatic tissue (medullary cords) separated by vessel-like spaces called medullary sinuses. Lymph travels to the lymph node via afferent lymphatic vessels and drains into the node just beneath the capsule in a space called the subcapsular sinus. The subcapsular sinus drains into trabecular sinuses and finally into medullary sinuses. The sinus space is criss-crossed by the pseudopods of macrophages which act to trap foreign particles and filter the lymph. The medullary sinuses converge at the hilum and lymph then leaves the lymph node via the efferent lymphatic vessel. Lymphocytes, both B cells and T cells, constantly circulate through the lymph nodes. They enter the lymph node via the bloodstream and may cross the wall of the bloodvessel by the process of diapedesis. The B cells migrate to the nodular cortex and medulla, and the T cells migrate to the deep cortex. When a lymphocyte recognizes an antigen, B cells become activated and migrate to germinal centers. When antibody-producing plasma cells are formed, they migrate to the medullary cords antigen

Lymph nodes of the head and neck

Anterior Cervical

These nodes, both superficial and deep, lie above and beneath the sternocleidomastoid muscles. They drain the internal structures of the throat as well as part of the posterior pharynx, tonsils, and thyroid gland.

Posterior Cervical

These nodes extend in a line posterior to the sternocleidomastoids but in front of the trapezius, from the level of the mastoid bone to the clavicle. They drain the skin on the back of the head. They are frequently enlarged during upper respiratory infections.

Tonsilar

These nodes are located just below the angle of the mandible. They drain the tonsilar and posterior pharyngeal regions.

Sub-mandibular

These nodes run along the underside of the jaw on either side. They drain the structures in the floor of the mouth.

Sub-mental

These nodes are just below the chin. They drain the teeth and intra-oral cavity.

Supraclavicular

These nodes are in the hollow above the clavicle, just lateral to where it joins the sternum. They drain a part of the thoracic cavity and abdomen. Virchow's node is a left supraclavicular lymph node which receives the lymph drainage from most of the body (especially the abdomen) via the thoracic duct and is thus an early site of metastasis for various malignancies.

Penicillin

:For the Japanese rock band, see Penicillin (band). Penicillin is a β-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually Gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Gram-positive Penicillin has a molecular formula R-C₉H₁₁N₂O₄S, where R is a variable side chain.

History

Penicillin was originally isolated from the Penicillium chrysogenum (formerly Penicillium notatum) mold. The antibiotic effect was originally discovered by a young French medical student Ernest Duchesne studying Penicillium glaucum in 1896, but his discovery was ignored by the Institut Pasteur. Another Institut Pasteur scientist, Costa Rican Dr. Clodomiro Picado Twight was the first to record the antibiosis effect of Penicillium in 1923. The serendipitous discovery was finally attributed to Scottish scientist Alexander Fleming in 1928, who noticed a halo of inhibition of bacterial growth around a contaminant blue-green mold on a Staphylococcus culture. Fleming concluded that the mold was releasing a substance that was inhibiting bacterial growth. He grew a pure culture and discovered that the fungus was Penicillium notatum — he later named the bacterial inhibiting substance penicillin after the Penicillium notatum that released it. Fleming was convinced after conducting some more experiments that penicillin could not last long enough in the human body to kill pathogenic bacteria and stopped studying penicillin after 1931. It would prove to be the discovery that changed modern medicine. In 1939, Australian Howard Walter Florey and a team of researchers at Oxford University made significant progress in showing Penicillin's in vivo ability to kill infectious bacteria. in vivo During World War II, penicillin made a major difference in the number of deaths and amputations caused by infected wounds amongst Allied forces. Availability was severely limited, however, by the difficulty of manufacturing large quantities of penicillin and by the rapid renal clearance of the drug necessitating frequent dosing. Penicillins are actively secreted and about 80% of a penicillin dose is cleared within three to four hours of administration. During those times it became common procedure to collect the urine from patients being treated so that the penicillin could be isolated and reused. (Silverthorn, 2004) This was not a satisfactory solution, however, so researchers looked for a way to slow penicillin secretion. They hoped to find a molecule that could compete with penicillin for the organic acid transporter responsible for secretion such that the transporter would preferentially secrete the competitive inhibitor. The uricosuric agent probenecid proved to be suitable. When probenecid and penicillin are concomitantly administered, probenecid competitively inhibits the secretion of penicillin, increasing its concentration and prolonging its activity. The advent of mass-production techniques and semi-synthetic penicillins solved supply issues, and this use of probenecid declined. (Silverthorn, 2004) Probenecid is still clinically useful, however, for certain infections requiring particularly high concentrations of penicillins. (Rossi, 2004) The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in the early 1940s, enabling synthetic production. A team of Oxford research scientists led by Australian Howard Walter Florey and including Ernst Boris Chain and Norman Heatley discovered a method of mass producing the drug. Florey and Chain shared the 1945 Nobel prize in medicine with Fleming for this work. Penicillin has since become the most widely used antibiotic to date and is still used for many Gram-positive bacterial infections.

Mode of action

Main article: beta-lactam antibiotic Other β-lactam antibiotics work by inhibiting the formation of peptidoglycan cross links in the bacterial cell wall. The beta-lactam moiety of penicillin binds to the enzyme(transpeptidase) that links the peptidoglycan molecules in bacteria, and this weakens the cell wall of the bacterium when it multiplies (in other words, the antibiotic causes cell cytolysis or death when the bacterium tries to divide).

Variants in clinical use

Benzathine penicillin

Benzathine penicillin is slowly absorbed into the circulation, after intramuscular injection, and hydrolysed to benzylpenicillin in vivo. It is the drug-of-choice when prolonged low concentrations of benzylpenicillin are required and appropriate, allowing prolonged antibiotic action over 2–4 weeks after a single IM dose. It is marketed by Wyeth under the trade name Bicillin®. Specific indications for benzathine pencillin include: (Rossi, 2004)
- prophylaxis of rheumatic fever
- early or latent syphilis

Benzylpenicillin (penicillin G)

syphilis Benzylpenicillin, commonly known as penicillin G, is the gold standard penicillin. Penicillin G is typically given by a parenteral route of administration because it is unstable to the hydrochloric acid of the stomach. Because the drug is given parenterally, higher tissue concentrations of penicillin G can be achieved than is possible with phenoxymethylpenicillin. These higher concentrations translate to increased antibacterial activity. Specific indications for benzylpenicillin include: (Rossi, 2004)
- bacterial endocarditis
- meningitis
- aspiration pneumonia, lung abscess
- community-acquired pneumonia
- syphilis
- septicaemia in children

Phenoxymethylpenicillin (penicillin V)

Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin, however, and is only appropriate in conditions where high tissue concentrations are not required. Specific indications for phenoxymethylpenicillin include: (Rossi, 2004)
- infections caused by Streptococcus pyogenes
- tonsilitis
- pharyngitis
- skin infections
- prophylaxis of rheumatic fever
- moderate-to-severe gingivitis (with metronidazole)

Procaine penicillin

Procaine penicillin (Bicillin®) is a combination of benzylpenicillin with the local anaesthetic agent procaine. This combination is aimed at reducing the pain and discomfort associated with a large intramuscular injection of penicillin. Specific indications for procaine penicillin include: (Rossi, 2004)
- respiratory tract infections where compliance with oral treatment is unlikely
- syphilis
- cellulitis

Adverse effects

Adverse drug reactions

Common adverse drug reactions (ADRs) for the penicillins include: diarrhea, nausea, rash, urticaria, superinfection (including candidiasis). (Rossi, 2004) Infrequent ADRs include: fever, vomiting, erythema, dermatitis, angioedema, pseudomembranous colitis. (Rossi, 2004) Pain and inflammation at the injection site is also common for parenterally-administered benzathine penicillin, benzylpenicillin, and to a lesser extent procaine penicillin.

Allergy/hypersensitivity

Allergic reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent. Anaphylaxis will occur in approximately 0.01% of patients. (Rossi, 2004) There is perhaps a 5-10% cross-sensitivity between penicillin-derivatives, cephalosporins and carbapenems; but this figure has been challenged by various investigators. Nevertheless, the risk of cross-reactivity is sufficient to warrant the contraindication of all β-lactam antibiotics in patients with a history of severe allergic reactions (urticaria, anaphylaxis, interstitial nephritis) to any β-lactam antibiotic.

Resistance

Antibiotic resistance to penicillin is now common amongst many hospital acquired bacteria. The resistance to penicillin has been partly due to the rise of beta-lactamase producing bacteria which secrete an enzyme that breaks down the beta-lactam ring of penicillin, rendering it harmless to the bacteria. These bacteria may remain sensitive to other beta-lactam antibiotics. Resistance also arises through modifications to the bacterial cell wall; this resistance usually extends to other beta-lactam antibiotics.

Developments from penicillin

The narrow spectrum of activity of the penicillins, along with the poor activity of the orally-active phenoxymethylpenicillin, led to the search for derivatives of penicillin which could treat a wider range of infections. The first major development was ampicillin, which offered a broader spectrum of activity than either of the original penicillins and allowed doctors to treat a broader range of both Gram-positive and Gram-negative infections. Further developments led to amoxicillin, with improved duration-of-action. Further development yielded beta-lactamase-resistant penicillins including flucloxacillin, dicloxacillin and methicillin. These were important for their activity against beta-lactamase-producing bacteria such as Staphylococcus species. It is still no match for MRSA (Methicillin Resistant Staphylococcus aureus). The last in the line of true penicillins were the antipseudomonal penicillins, such as ticarcillin and piperacillin, useful for their activity against Gram-negative bacteria. However, the usefulness of the beta-lactam ring was such that related antibiotics, including the mecillinams, the carbapenems and, most importantly, the cephalosporins, have it at the centre of their structures.

Biosynthesis

cephalosporin The precursor compound ACV-tripeptide (δ-(L-α-amino-adipate)-L-cysteine-D-valine) is biosynthesized in bacteria and fungi from the monomeric L-amino acids by the enzyme ACV-synthetase (EC 6.3.2.26), a nonribosomal peptide synthetase. The ACV-tripeptide is cyclized by isopenicillin-N-synthetase (EC 1.21.3.1) to isopenicillin N, thereby forming the beta-lactam nucleus. The isopenicillin N N-acyltransferase (EC 2.3.1.164) exchanges the sidechain, yielding a broad range of different penicillins depending on the utilized CoA-bound carboxylic acids. The synthesis of the cephalosporin-type antibiotics starts with isopenicillin N. (Moss, 2002)

References

- Moss GP (2002). [http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/penicillin.html Penicillin biosynthesis]. Retrieved 6 December 2004.
- Rossi S (Ed.) (2004). Australian Medicines Handbook 2004. Adelaide: Australian Medicines Handbook. ISBN 0-9578521-4-2.
- Silverthorn DU (2004). Human Physiology: An Integrated Approach (3 ed.). Pearson Education. ISBN 0-8053-5957-5 Category:Beta-lactam antibiotics ko:페니실린 ja:ペニシリン

Erythromycin

Erythromycin is a macrolide antibiotic which has an antimicrobial spectrum similar or slightly wider to that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea. Structurally, this macrocyclic compound contains a 14-membered lactone ring with ten asymmetric centers and two sugars (L-cladinose and D-desoamine), making it a compound very difficult to produce via synthetic methods. Erythromycin is produced from a strain of the actinomyces Saccaropolyspora erythraea, formerly known as Streptomyces erythraeus.

History

Abelardo Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate Erythromycin from the metabolic products of a strain of Streptomyces erythreus found in the samples. The product was subsequently launched in 1952 under the brand name Ilosone® (after the Philippine region of Iloilo where it was originally collected from). Erythromycin was formerly also called Ilotycin®. In 1981, Nobel laurate (1965 in chemistry) and Professor of Chemistry at Harvard University (Cambridge, MA) Robert B. Woodward and a large team of researchers reported the first stereocontrolled asymmetric chemical synthesis of Erythromycin A.

Available forms

Erythromycin is available in enteric-coated tablets, oral suspensions, opthalmic solutions, ointments, gels and injections.

Mechanism of action

Erythromycin prevents bacteria from growing, by interfering with their protein synthesis. Erythromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translation of peptides.

Pharmacokinetics

Erythromycin is easily inactivated by gastric acids, therefore all orally administered formulations are given as either enteric coated or as more stable salts or esters. Erythromycin is very rapidly absorbed, and diffused into most tissues and phagocytes. Due to the high concentration in phagocytes, erythromycin is actively transported to the site of infection, where during active phagocytosis, large concentrations of erythromycin are released.

Metabolism

Most of erythromycin is metabolised by demethylation in the liver. Its main route elimination route is in the bile, and a small portion in the urine. Erythromycin's half-life is 1.5 hours.

Side-effects

Gastrointestinal intestinal disturbances such as diarrhea, nausea, abdominal pain and vomiting are fairly common so it tends not to be prescribed as a first-line drug. More serious side-effects, such as reversible deafness are rare. Cholestatic jaundice, Stevens-Johnson syndrome and toxic epidermal necrosis are some other rare side effects that may occur. Erythromycin has been shown to increase the probability of pyloric stenosis in children whose mothers took the drug during the late stages of pregnancy or while nursing.

Contraindications

Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link between erythromycin, ventricular tachycardia and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem) by interfering with CYP3A4 (Ray et al 2004). Hence, erythromycin should not be administered in patients using these drugs, or drugs that also prolong the QT time. Other examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the QT time) and pimozide (Orap).

References

- Ray WA, Murray KT, Meredith S, Narasimhulu SS, Hall K, Stein CM. Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes. N Engl J Med 2004;351:1089-96.
- British National Formulary "BNF 49" March 2005. Category:Macrolide antibiotics

Red Cross

emblems, the symbols from which the Movement derives its name]] The International Red Cross and Red Crescent Movement consists of the International Committee of the Red Cross (ICRC), the International Federation of Red Cross and Red Crescent Societies (Federation), and the 183 national Red Cross or Red Crescent societies currently recognized by the ICRC and admitted as full members of the Federation. All of these organizations are legally independent from each other, but are united within the movement through common basic principles, objectives, symbols, statutes, and governing organs. The movement is voluntary and

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