I am doing a novel packet on "The Boy in the Striped Pajamas" and in the packet it asks to include all literary devices, but I do not understand...

Literary devices are any tools the writer uses to make the writing clearer, more vivid, and more enjoyable to read, and to give the story more depth. There are actually hundreds of literary devices. I'll give you a few examples of some of the most common literary devices that you can find in The Boy in the Striped Pajamas.

Imagery: Imagery means the writer writes description so vividly that you have an image, or picture, in your mind as you are reading. There are a lot of kinds of imagery. Imagery can be visual, which creates a picture you can see in your mind's eye. Other kinds of imagery include tactile (what you can feel), aural (what you can hear), olfactory (what you can smell), and gustatory (what you can taste.) You can find lots of imagery in The Boy in the Striped Pajamas. The first example of imagery is in the very first paragraph of Chapter 1, describing Maria, the family's maid: "... always kept her head bowed and never looked up from the carpet...." When you read this, you have a mental image of a maid standing with her head down, looking at the carpet. This imagery not only tells you something about Maria's appearance, it also tells you something about her character: she is shy and introverted.

Metaphor: Another literary device that is linked to imagery and used frequently is metaphor. A metaphor occurs when the writer describes something by comparing it to something else. A simile is a type of metaphor. You can remember the difference between these two similar literary devices because a metaphor is structured to say something IS something else, while a simile is structured to say something IS LIKE something else. A simile can also be structured to say something IS AS... AS something else, for example as tall as a tree or as big as a house.

When Bruno is showing Gretel the view out his window, he uses a metaphor: "...he was the king of everything they surveyed and she was his lowly subject." This metaphor compares Bruno to a king and Gretel to a servant. It shows that Bruno feels smug about having discovered something that his older sister didn't understand. It also reveals something about his character: Bruno is used to being the littlest in the family, so when he has an opportunity to be significant in some way, it makes him feel very important and powerful.

When Bruno sees his father with a group of soldiers, he uses a simile: "... they stood in a row together like toy soldiers...." This simile compares the men to toy soldiers, and when you read this simile, you can imagine the men standing in the same position as one another and looking very similar to each other.

Hyperbole: Another literary device that is used frequently in The Boy in the Striped Pajamas is hyperbole. Hyperbole is an exaggeration. Bruno, the protagonist, is young, and the hyperbole has the effect of reminding the reader that the protagonist is just a little boy, because little children tend to exaggerate or see things as bigger than they actually are. Bruno uses hyperbole to describe his father's voice: "... there had never been a man born who was more capable of being heard from one side of a room to the other as father." This hyperbole shows that Bruno's father has a loud, powerful voice. It also gives the reader some insight into Bruno's father's character. He is a powerful man and influential on everyone around him.

has a handout listing some of the more common literary devices, which you can view by . You can also read more about the novel The Boy in the Striped Pajamas . 

What is the main idea in the Outliers epilogue chapter, "A Jamaican Story"?

Gladwell has spent the entire book talking about other people’s success stories and what elements had to be in place in order to give preference to the “outliers” in these circumstances. Now it’s time to share his own story. Or rather, his mother’s. Joyce Nation grew up in Jamaica. She and her twin sister won scholarships to attend a boarding school called Saint Hilda’s, then later went to college in London. There Joyce met Graham...

Gladwell has spent the entire book talking about other people’s success stories and what elements had to be in place in order to give preference to the “outliers” in these circumstances. Now it’s time to share his own story. Or rather, his mother’s. Joyce Nation grew up in Jamaica. She and her twin sister won scholarships to attend a boarding school called Saint Hilda’s, then later went to college in London. There Joyce met Graham Gladwell, a math professor whom she later married and moved with to Canada. But of course, the story is not quite this simple. A number of factors had to be just right for this meeting to happen and for our author Malcolm to be born. It’s a fascinating history that boils down to matters of race, skin color, and educational practices within the island culture. The main idea of the chapter turns out to be a brief history of 20th-century life in Jamaica.

Adding this chapter and putting it last is a terrific technique with which to conclude this book. Gladwell is putting himself into the text, showing that no one is immune to these kinds of “outlier” events, not even the journalist reporting on them. He also allows each one of us to think about our own backgrounds and our own cultural legacies. What were the special circumstances that had to happen in order for each one of us to be born? We are given much to think about here, even after closing the covers of the book.

By the end of Act 5, Malcolm seems to have earned the kingship of Scotland. Is he more noble and righteous than Macbeth? Is he more like his father...

Malcolm is most definitely more noble and righteous than Macbeth is, and he is much more like his father than Macbeth is as well.  When Macduff comes to the English court to fetch him back to Scotland, Malcolm initially tests Macduff's honesty to make sure Macbeth hasn't sent him to lead Malcolm back like a lamb to the slaughter.  After Macduff has proven his loyalty to Scotland, Malcolm says, "But God above / Deal between thee and me, for even now / I put myself to thy direction and / Unspeak mine own detraction, here abjure / The taints and blames I laid upon myself / For strangers to my nature" (4.3.139-144).  In other words, all the terrible things he's told Macduff about himself are untrue.  He's not greedy at all, is still a virgin, has never lied, and loves the truth.  Macbeth is avaricious and power-hungry; Malcolm is not.  Macbeth is a practiced liar; Malcolm has never lied until this moment.

Moreover, Malcolm says, "What I am truly / Is thine and my poor country's to command" (4.3.150-151).  He longs to serve his country, not to exploit it and tyrannize it as Macbeth has done.  Scotland, he says, will command him and not the reverse.  Macbeth is so power-hungry that he killed to acquire power and killed to keep it; Malcolm has never done such a thing.

Further, after Macduff has killed Macbeth, Malcolm gives a speech to those who were loyal to him.  He says, "We shall not spend a large expense of time / Before we reckon with your several loves / And make us even with you" (5.8.72-74).  In other words, he will reward those who were loyal to him with new titles and lands, just as his father did when he made Macbeth the Thane of Cawdor. 

Malcolm is actually even a little better, a little wiser and more worldly than his father was.  Duncan was deceived in the first Thane of Cawdor and in Macbeth as well.  About the traitorous Thane of Cawdor, he'd said, "There no art / To find the mind's construction in the face" (1.4.13-14).  He laments that one cannot simply tell what another person is thinking based on looking at them.  Malcolm seems to take precautions against being deceived in a way that his father never really did (as he does when he tests Macduff's loyalty, as I referred to above).  This bodes well for his kingship; Duncan was a wonderful king, but it seems as though Malcolm will be even better: he'll reward those who are loyal to him and he's less likely to be deceived by traitors.

What is the diaphragm? |

Structure and Functions

The diaphragm is attached to the spine, the ribs, and the sternum. It is pierced by the esophagus, the phrenic nerve, the aorta, and the vena cava. The human body has three types of muscles: cardiac, which is striated and under involuntary control; smooth, which is not striated and is under involuntary control; and skeletal, which is striated and under voluntary control. The diaphragm is composed of skeletal muscle and is under both voluntary and involuntary control. That is, one is able to hold the breath, take deeper breaths, or take faster breaths (panting), examples of voluntary control. However, a person normally breathes, allowing the diaphragm to contract and relax as skeletal muscle does, involuntarily—that is, without the conscious effort that is required with holding one’s breath.

As skeletal muscle, the diaphragm must be innervated; that is, it must receive a nerve impulse before it will contract. The impulses that are sent to the diaphragm originate in the higher brain centers when one voluntarily controls breathing but originate in the lower brain when low oxygen concentrations or high carbon dioxide concentrations are present. The diaphragm relies on the phrenic nerve for its innervations.

When innervated, the diaphragm contracts, as all skeletal muscle does, and flattens or pulls downward. This movement serves to cause the ribs to pull outward, increasing the volume within the lungs. Air pressure inside the lungs is now lower than air pressure outside the lungs (the environment), so air rushes in. As the diaphragm muscle relaxes, it once again domes upward, allowing the ribs to move back to a resting position. The lung volume decreases, but since the lungs are filled with air, the pressure inside the lungs is now greater than the pressure outside the lungs. Air moves outward as one exhales. (This simple expansion and contraction of the lung volume is the premise behind the original iron lung machine.) This cycle of contraction and relaxation is repeated approximately twelve to fourteen times per minute; with heavy exercise, it may be repeated forty times per minute.

The diaphragm has a role in laughing, singing, crying, yawning, hiccupping, vomiting, coughing, sneezing, whistling, defecating, and urinating, as well as in childbirth.

Disorders and Diseases

The diaphragm may be affected by both neurological and anatomical processes. Common neurological problems are disorders of innervation as a result of trauma to the head or brain stem; nerve impulses to the diaphragm are disrupted and the diaphragm cannot contract and relax. These injuries are often fatal. Poliomyelitis, demyelinating diseases, and other diseases may also impair the innervation of the diaphragm. Anatomical problems may include hernias (protrusion of the stomach through the diaphragm and into the thoracic cavity). Blunt trauma from car accidents and the like may rupture the diaphragm.

Bibliography

Koch, Wijnand F. R. M., and Enrico Marani. Early Development of the Human Pelvic Diaphragm. New York: Springer, 2007.

Kohnle, Diana, Marcin Chwistek, and Brian Randall. "Diaphragmatic Hernia." Health Library, March 18, 2013.

"Lungs and Breathing." MedlinePlus, June 26, 2013.

Marieb, Elaine N. Essentials of Human Anatomy and Physiology. 10th ed. San Francisco: Pearson/Benjamin Cummings, 2012.

Sherwood, Lauralee. Human Physiology: From Cells to Systems. 8th ed. Belmont, Calif.: Brooks/Cole/Cengage Learning, 2013.

How are checks and balances important to maintaining a democracy?

When the Constitution was being written, the delegates to the Constitutional Convention believed a system of checks and balances was needed to maintain our democracy. The purpose of having a system of checks and balances is to prevent any branch of government or any person in government from becoming too powerful. We fought against the British because we felt the King had too much power and abused the rights of the colonists. The delegates wanted to create a plan of government that was stronger than the government created by the Articles of Confederation, but not one that had too much power.

In our system of government, Congress makes the laws. However, to prevent Congress from abusing its lawmaking power, the President has to sign a bill into law. If the President is against the law, he can veto it. This prevents the bill from becoming law. However, if Congress really believes the law is a good one and should go into effect, Congress can override the veto by having two-thirds of both houses of Congress vote to approve the vetoed bill.

Another example of the system of checks and balances can be seen with treaties. The President can negotiate a treaty. However, in order for the treaty to be accepted, the Senate must approve the treaty. This process limits the power of the President.

There are many examples of checks and balances in our system of government. The goal is to prevent any part of the government or any person in our government from becoming too powerful.

What is touch deprivation? |

Touch deprivation is a condition that involves little or no stimulation by way of physical contact with other people. Human touch has been proven to be vital to emotional, psychological, and physical growth in infants and to some extent in older children and adults. Deprivation can cause developmental deficiencies in babies. Studies have shown that in extreme cases, touch deprivation can lead to infant death. In adults and older children, touch deprivation is related to conditions such as depression, aggression, and eating disorders.

Studies on Touch Deprivation

In early development and behavior studies of the 1950s, Harry F. Harlow completed several experiments with rhesus monkeys that involved separating newborns from their mothers. Each baby lived with surrogates in the form of either a wire mother shape equipped with a feeding bottle or a similar form that was soft and padded. Invariably, the babies preferred the soft, comforting mother, visiting the wire dummy only to feed. However, all the monkeys developed abnormal behavioral patterns and reactions as they grew up. Even when the babies were able to see and hear other monkeys, they did not develop normally.

Since then, numerous studies have shown that touch deprivation has serious effects on human babies and young children. In the late nineteenth and early twentieth centuries, the mortality rate of babies in institutions, including hospitals, was nearly 100 percent. Because they were separated from their parents, isolated in cribs, and rarely picked up, these infants suffered acute stress in addition to their medical conditions. As recently as the 1990s, young children in Romanian orphanages were found to be physically undersized and emotionally unresponsive after lives deprived of sensory stimulation, especially touch. Even after being adopted, some children were unable to develop close attachments to parents and siblings.

Studies also reveal that touch—especially skin-to-skin contact—between parents and babies is beneficial to both. Stress hormones drop and babies cry less and sleep more soundly. Mothers who held their babies reported less stress and depression. Adults also benefit physically and emotionally from touch, including massage, hugging, and sexual intimacy.

Animal studies have shown that depriving young mammals of normal maternal care and socialization results in depression, withdrawal, violence, aggression, and other emotional disorders, which researchers attributed to touch deprivation. Such behavioral aberrations in humans have been tied to deficits in the cerebellum, whether from lack of sensory stimulation or congenital malfunction that prevents the normal desire for touch.

Measuring Touch Deprivation

Several methods have been used to evaluate touch deprivation. The Touch Deprivation Scale, developed by Jason S. Wrench and Narissra M. Punyanunt-Carter, is a questionnaire that asks participants to read about touch deprivation and then rate their own experiences to various statements on the sixteen-question form. The measurement uses a five-degree scale ranging from "strongly disagree" to "strongly agree" to find any correlations between touch deprivation and early nurturing, depression, self-esteem, and same-sex touching. The results of a survey of about two hundred undergraduate students showed that a significant number of participants longed for touch and nurturing. It also found a connection between touch deprivation and depression and low self-esteem.

Touch deprivation also shows up in blood hormone analyses. Higher levels of cortisol, a stress hormone, were measured in young children living in conditions of touch deprivation. Their cortisol levels remained high even after months of fostering. However, in most instances where high blood cortisol levels were measured, touching lowered them significantly.

Symptoms of Touch Deprivation

Babies deprived of touch may suffer from a condition called
failure to thrive
. Even if a child receives adequate nourishment and is kept clean and safe, his or her physical and psychological growth is affected in the absence of a caregiver's frequent loving touch. After the prominent nineteenth-century pediatrician Dr. Luther Emmett Holt published his book The Care and Feeding of Children, parents took to heart Holt's advice to avoid "indulging" the baby's cries to be rocked or carried, as it would lead to bad habits. Doctors soon noticed more babies, though seemingly well fed and cared for, were failing to thrive as a result of touch deprivation. Less significant deprivation, while not fatal, has been found to contribute to withdrawal, aggression, or other long-term behavioral irregularities.

Adults also suffer if they lack sufficient physical contact with others. Depression is closely linked to touch deprivation in adults, and research has established associations between touch deprivation and eating disorders. Men are more likely to suffer from touch deprivation than women because of stronger social prohibitions against same-sex touching among adult males.

Relieving Touch Deprivation

The simplest remedy for insufficient touch is to touch and invite touch from family members and friends. However, some people lack close relationships or find touching friends awkward or uncomfortable. A popular way to increase touch is through massage therapy. Massage provides not only the therapeutic kneading of muscles, but also skin contact with another person. Proponents of massage believe its growing acceptance among health care professionals shows its value in healing and pain reduction, in addition to easing depression. Controlled studies testing the effects of massage on a variety of physical ailments consistently showed improvement in such symptoms as elevated blood pressure, anxiety, and pain. Children with conditions such as autism and attention-deficit/hyperactivity disorder also benefited, showing improved behavior and concentration after two weeks of massage therapy.

Bibliography

Bruce, Debra Fulghum. "How Can Lack of Touch Lead to Babies’ Failure to Thrive?" Sharecare. Sharecare. Web. 27 Mar. 2015. http://www.sharecare.com/health/kids-teens-health/lack-of-touch-failure-thrive

Gupta, Madhulika A., Aditya K. Gupta, Nicholas J. Schork, and Gena N. Watteel. "Perceived Touch Deprivation and Body Image: Some Observations Among Eating Disordered and Non-Clinical Subjects." Journal of Psychosomatic Research, Vol. 39, No. 4. 459-464. Elsevier Science Ltd. 1995. Web. 30 Mar. 2015. http://www.inharmonytoday.com/wp-content/uploads/2012/01/Perceived-touch-deprivation-in-eating-disordered-patients.pdf

Harmon, Katherine. "How Important Is Physical Contact with Your Infant?" Scientific American. Scientific American, a Division of Nature America, Inc. 6 May 2010. Web. 27 Mar. 2015. http://www.scientificamerican.com/article/infant-touch/

Prescott, James W. "Early Somatosensory Deprivation as an Ontogenetic Process in the Abnormal Development of the Brain and Behavior." Origins of Peace and Violence. Erik Möller and Colleagues. 2004. Web. 27 Mar. 2015. http://www.violence.de/prescott/mp/article.html

Schultheis, Erin. "Harry F. Harlow." Muskingum College Psychology Department. Muskingum University. May 1999. Web. 30 Mar. 2015. http://muskingum.edu/~psych/psycweb/history/harlow.htm

Wrench, Jason S. and Narissra M. Punyanunt-Carter. "Touch Deprivation Scale." Human Communication, Vol. 12 No. 1. 67-76. University of Alabama Birmingham. 2006. Web. 30 Mar. 2015. http://www.uab.edu/Communicationstudies/humancommunication/12_05_Carter_Wrench.pdf

When the niches of two or more species overlap, why will one go extinct?

If the niches (or functional roles) of 2 species in an ecosystem are identical, then one of them will go extinct. This is known as the competitive exclusion principle and was demonstrated by Gause's experiment with Paramecia. When grown in isolation, the two species that he used followed the normal growth curve, eventually each reaching their carrying capacity. However, when both were grown in a test tube together, one always outcompeted the other so that one...

If the niches (or functional roles) of 2 species in an ecosystem are identical, then one of them will go extinct. This is known as the competitive exclusion principle and was demonstrated by Gause's experiment with Paramecia. When grown in isolation, the two species that he used followed the normal growth curve, eventually each reaching their carrying capacity. However, when both were grown in a test tube together, one always outcompeted the other so that one species survived and the other went extinct in the tube. Whether the surviving species was P. aurelia or P. caudatum depended on the environmental conditions within the test tube. This occurs in nature as well because two species with overlapping niches are going to be in competition for all of their resources including food and space.

Competitive exclusion does not always occur, however. Niche partitioning can allow similar species to coexist within a particular environment. This allows coexistence of species with similar niches because, when it occurs, the realized niche is smaller than the fundamental niche for each species allowing them to divide the resource. For example, if there are similar species of bird and their fundamental niche involves utilization of an entire tree, niche partitioning allows them to coexist if the realized niche of each species is now a smaller portion of the tree so that there is minimal overlap between these realized niches.

The link provided goes to a website with figures showing both situations.

What are probiotics? |

Overview

Lactobacillus acidophilus is a friendly strain of bacteria used to make yogurt and cheese. Although humans are born without it, acidophilus soon establishes itself in the intestines and helps prevent intestinal infections. Acidophilus also flourishes in the vagina, where it protects girls and women from yeast infections.

Acidophilus is one of several microbes known collectively as probiotics (meaning “pro life”), indicating that they are bacteria and yeasts that help rather than harm. Other helpful microbes include the yeast Saccharomyces boulardii and the bacteria L. bulgaricus, L. reuteri, L. plantarum, L. casei, B. bifidum, Streptococcus salivarius, and S. thermophilus.

The digestive tract contains billions of bacteria and yeasts. Some of these
internal inhabitants are more helpful to the body than others. Acidophilus and
related probiotics not only help the digestive tract function but also reduce the
presence of less healthful organisms by competing with them for the limited space
available. For this reason, the use of probiotics can help prevent infectious
diarrhea.

Antibiotics can disturb the balance of the digestive tract by killing friendly bacteria. When this happens, harmful bacteria and yeasts can move in and flourish. This can lead to vaginal yeast infections (Candida albicans). Conversely, it appears that the regular use of probiotics can help prevent vaginal infections and generally improve the health of the gastrointestinal system. Persons taking antibiotics should probably take probiotics too and should continue probiotics for some time after treatment with antibiotics.

Sources

Although probiotic bacteria are helpful and perhaps even necessary for human health, no daily requirement exists. Probiotics are living creatures, not chemicals, so they can sustain themselves in the body unless something comes along to damage them, such as antibiotics.

Cultured dairy products such as yogurt and kefir are good sources of acidophilus and other probiotic bacteria. Supplements are widely available in powder, liquid, capsule, or tablet form. Grocery stores and natural food stores sell milk that contains live acidophilus. In addition to probiotics, related substances known as prebiotics may enhance the colonization of healthy bacteria in the intestinal tract.

Therapeutic Dosages

Dosages of acidophilus are expressed not in grams or milligrams (mg) but in billions of organisms. A typical daily dose should supply about three to five billion live organisms. Other probiotic bacteria are used similarly. The typical dose of S. boulardii yeast is 500 mg twice daily (standardized to provide 3 x 1010 colony-forming units per gram), to be taken while traveling or at the start of using antibiotics and to be continued for a few days after antibiotics are stopped.

Because probiotics are not drugs but rather living organisms that a person is trying to transplant to the digestive tract, it is necessary to take the treatment regularly. Each time this is done, beneficial bacterial colonies in the body are reinforced, so that they can gradually push out harmful bacteria and yeasts.

Probiotics, as living organisms, may die on the store shelf. A study reported in 1990 found that most acidophilus capsules on the market contained no living acidophilus. The situation has improved in subsequent evaluations, but some products remain substandard. The container label should guarantee living organisms at the time of purchase, not just at the time of manufacture. Another approach is to eat acidophilus-rich foods such as yogurt, in which the bacteria are most likely still alive.

To treat or prevent vaginal infections, one can mix two tablespoons of yogurt or the contents of a couple of capsules of acidophilus with warm water. This mixture can then be used as a douche.

Finally, in addition to increasing one’s intake of probiotics, a person can take
fructo-oligosaccharides, supplements that can promote
thriving colonies of helpful bacteria in the digestive tract.
Fructo-oligosaccharides are carbohydrates found in fruit. Fructo
means “fruit” and an “oligosaccharide” is a type of carbohydrate. Taking this
supplement is like putting manure in a garden; it is thought to foster a healthy
environment for the bacteria. The typical daily dose of fructo-oligosaccharides is
between 2 and 8 grams.

Therapeutic Uses

Evidence from many double-blind, placebo-controlled trials suggests that probiotics may be helpful for many types of diarrhea and for irritable bowel syndrome. Additionally, probiotics have shown some promise for preventing or treating eczema.

Probiotics may be helpful for controlling symptoms and maintaining remission in ulcerative colitis. However, probiotics may be less useful for inducing remission. For example, when probiotics were added to standard medications used for induction of remission, no additional benefits were seen in a study of people with mild-to-moderate ulcerative colitis.

Probiotics might help prevent colds, possibly by improving immunity. On a related note, one small double-blind study found evidence that the use of the probiotic bacterium L. fermentum improved the effectiveness of the influenza vaccine. The probiotic supplement was taken in two doses. One was taken two weeks before the vaccine, and the other was taken two weeks after.

Although probiotics are widely used to prevent or treat vaginal yeast infections, evidence regarding potential benefit remains incomplete and inconsistent. A small trial of fifty-five women with vulvovaginal candidiasis did demonstrate that daily L. rhamnosus and L. reuteri supplementation for four weeks, combined with single-dose fluconazole (an antifungal medication), decreased symptoms compared with fluconazole alone. Another large and well-designed trial, however, failed to find a Lactobacillus preparation helpful for preventing yeast infections caused by antibiotics. One study did find that probiotics might reduce levels of C. albicans in the mouth.

The bacterium Gardnerella vaginalis can cause a different type of vaginal infection. As with vaginal yeast infections, probiotics have shown some promise for this condition, but evidence remains inconclusive. A trial of sixty-four women taking a single dose of tinidazole for bacterial vaginosis suggests that women who also took daily probiotics capsules had better cure rates at four weeks. A larger trial involving 120 women with a history of bacterial vaginosis found that taking one capsule daily of the probiotics L. rhamnosus, acidophilus, and S. thermophilus reduced recurrence.

The bacterium
Helicobacter pylori
is the main cause of ulcers in the stomach and duodenum. Antibiotics can kill H. pylori, but more than one type of antibiotic must be used at the same time. Even in this case, the bacteria are not necessarily eradicated. Probiotics may be helpful for this. Evidence suggests that various probiotics can inhibit the growth of H. pylori. While this effect does not appear to be strong enough for probiotic treatment to eradicate H. pylori on its own, preliminary evidence, including several small double-blind trials, suggests that various probiotics may help standard antibiotic therapy work better, reducing side effects and possibly increasing the rate of eradication.

Some preliminary double-blind trials suggest that probiotics might improve cholesterol profile. Various probiotics might be helpful for allergic rhinitis (hay fever).

Milk fermented by probiotics may slightly improve blood pressure levels. While there is some evidence that probiotics can help reduce symptoms of milk allergies, one study found that adding probiotics to cow’s milk formula for infants was not helpful. One study found that the use of probiotics during pregnancy and breast-feeding may decrease the likelihood that a highly allergic nursing mother will pass her allergic tendencies to her breast-fed infant.

One double-blind, placebo-controlled study of seventy people with chronic constipation found some evidence of benefit with L. casei Shirota. Another study found that L. rhamnosus was helpful for chronic constipation in children. A small trial also found benefits in children, this time with a mixture of bifidobacteria and lactobacilli. In another study, a combination of B. lactis and B. longus showed promise for improving bowel regularity in residents of nursing homes. Finally, in a six-week, double-blind, placebo-controlled trial of 274 people with constipation-predominant irritable bowel syndrome, the use of a probiotic formula containing B. animalis significantly improved stool frequency.

A preliminary double-blind, placebo-controlled study found evidence that Lactobacillus GG might potentially be helpful for treating antibiotic-resistant bacteria. This small study followed twenty-three people with severe kidney disease who tested positive for vancomycin-resistant bacteria in the stool. (Vancomycin is one of the main final-option antibiotics for the treatment of resistant bacteria.) The use of a yogurt product containing L. rhamnosus appeared to be more effective at ridding the gastrointestinal tract of these bacteria than did placebo. However, the study had a number of flaws, especially its small size. Note also that participants in this study did not have active infection with antibiotic-resistant bacteria; they were carriers for it. One should not attempt to use probiotics as the sole treatment for active infection with resistant bacteria. The preventive use of probiotics does not appear to help prevent the development of resistant bacterial strains that may arise during antibiotic treatment.

Probiotic treatment has also been proposed as a treatment for canker sores and as a preventive measure against colon cancer, but there is no solid evidence that it is effective. One study found that giving probiotics to certain critically ill people could help prevent multiple organ failure.

Probiotics have shown some promise for helping to prevent cavities by antagonizing cavity-causing bacteria. An open study found hints that probiotics might be helpful for mouth sores caused by Behçet’s syndrome. One small, placebo-controlled study found that the use of L. helveticus might improve sleep quality in the elderly, for reasons that are not clear.

Probiotics have shown some promise in the treatment of infections with the yeast C. albicans. Probiotics are also proposed for the treatment of a theoretically related, but markedly controversial, condition known as candida hypersensitivity syndrome (also known as chronic candidiasis, chronic candida, systemic candidiasis, yeast hypersensitivity syndrome, and candida). As described by some alternative medicine practitioners, yeast hypersensitivity syndrome is a common problem that consists of a population explosion of the normally benign candida yeast that live in the vagina and elsewhere in the body, coupled with a type of allergic sensitivity to it. Probiotic supplements are widely recommended for this condition because they establish large, healthy populations of friendly bacteria that compete with the candida. However, there is no evidence that yeast hypersensitivity is a common problem and virtually no evidence that it exists at all.

In one small, twelve-week study, Lactobacillus GG failed to prove more effective than placebo for the treatment of rheumatoid arthritis. Another study failed to find Lactobacillus GG helpful for dyspepsia (generic stomach pain of unknown origin) in children.

A one-year-long open trial of 150 women failed to find Lactobacillus probiotics effective for preventing urinary tract infections, compared with cranberry juice or no treatment. Other studies, however, including a large (453-participant), three-month, double-blind, placebo-controlled study of a special healthful
Escherichia coli
probiotic did find benefits.

A substantial study failed to find a mixture of L. casei, L. bulgaricus, and S. thermophilus in yogurt and milk helpful for asthma in children. However, another study found that the combination of a probiotic (B. breve) and a prebiotic (galacto- and fructo-oligosaccharide) may help reduce wheezing in infants with eczema.

Scientific Evidence

Travelers’ diarrhea. According to several studies, it appears
that the regular use of acidophilus and other probiotics can help prevent
travelers’
diarrhea, an illness caused by eating contaminated food,
usually in developing countries. One double-blind, placebo-controlled study
followed 820 people traveling to southern Turkey and found that the use of
Lactobacillus GG significantly protected against intestinal
infection.

Other studies using S. boulardii, including a double-blind, placebo-controlled trial enrolling three thousand Austrian travelers, found similar benefits. The greatest benefits were seen in travelers who visited North Africa and Turkey. The researchers noted that the benefit depended on consistent use of the product, and that a dosage of 1,000 mg daily was more effective than 250 mg daily.

Infectious diarrhea. Probiotics may also help prevent or treat acute infectious diarrhea in children and adults. A review of the literature published in 2001 found thirteen double-blind, placebo-controlled trials on the use of probiotics for acute infectious diarrhea in infants and children; ten of these trials involved treatment, and three involved prevention. Overall, the evidence suggests that probiotics can significantly reduce the duration of diarrhea and perhaps help prevent it. The evidence is strongest for the probiotic Lactobacillus GG and for infection with a particular virus, rotavirus, which causes severe diarrhea in children.

One double-blind, placebo-controlled trial of 269 children (aged one month to three years) with acute diarrhea found that those treated with Lactobacillus GG recovered more quickly than those given placebo. The best results were seen among children with rotavirus infection. Similar results with Lactobacillus GG were seen in a double-blind study of seventy-one children. However, 224 young Chinese children with severe, acute diarrhea found no benefit from lactose-free formula supplemented with bifidobacteria and S. thermophilus, suggesting that probiotics may not be as useful for cases of severe, dehydrating diarrhea. Also, L. rhamnosus GG is not always associated with improvement. When given for ten days to 229 infants from rural India who were hospitalized with acute diarrhea, the probiotic did not reduce the severity of the diarrhea during that time period.

In addition, a double-blind study evaluated the possible benefits of the probiotic L. reuteri in sixty-six children with rotavirus diarrhea. The study found that treatment shortened the duration of symptoms and that the higher the dose, the better the effect. Similar benefits were seen in a placebo-controlled trial of 151 infants and children given the probiotic E. coli Nissle 1917 (a safe strain of E. coli) for twenty-one days for nonspecific (presumably viral) cases of mild to moderate diarrhea.

A double-blind, placebo-controlled study of eighty-one hospitalized children found
that treatment with Lactobacillus GG reduced the risk of
developing diarrhea, particularly rotavirus infection. A double-blind,
placebo-controlled study found that Lactobacillus GG helped
prevent diarrhea in 204 undernourished children.

Other studies generally (though not consistently) indicate that the probiotics B. bifidum, S. thermophilus, L. casei, Lactobacillus LB, and S. boulardii (individually and combined with L. reuteri and L. rhamnosus) may also help prevent or treat diarrhea in infants and children. One study found that bacteria in the B. bifidum family can kill numerous bacteria that cause diarrhea.

A large (211-participant), double-blind, placebo-controlled study found that adults with diarrhea also can benefit from probiotic treatment. Another study found that the regular use of probiotics could help prevent gastrointestinal infections in adults.

Antibiotic-related diarrhea. The results of many double-blind and open trials suggest that probiotics, especially S. boulardii and Lactobacillus GG, may help prevent or treat antibiotic-related diarrhea. For example, one study evaluated 180 people, who received either placebo or 1,000 mg of Saccharomyces daily with their antibiotic treatment, and found that the treated group developed diarrhea significantly less often. A similar study of 193 people also found benefit.

A minimum of three more studies involving adults found that various species of Lactobacillus, taken either alone or in combination, were beneficial, even in cases of
Clostridium difficile infection, the most serious type of antibiotic-induced diarrhea. However, a study of 302 people found no benefit with Lactobacillus GG. A review of four probiotic studies found insufficient evidence for their effectiveness in the treatment of C. difficile. Finally, although taking probiotic organisms in the proper concentration may be beneficial for antibiotic-induced diarrhea, one study found that consuming fresh yogurt during antibiotic treatments had no significant effect on the incidence of diarrhea.

Other forms of diarrhea. Two double-blind, placebo-controlled studies enrolling almost seven hundred people undergoing radiation therapy for cancer found that the use of probiotics significantly improved radiation-induced diarrhea. Similar evidence supports the use of L. rhamnosus and a special, nonpathogenic form of E. coli. However, of eighty-five women receiving pelvic radiation for cervical or uterine cancer, those who consumed a liquid yogurt preparation enriched with L. casei had no less diarrhea than those who took a placebo drink. Small double-blind studies suggest that S. boulardii might be helpful for treating chronic diarrhea in people with human immunodeficiency virus infection, in persons hospitalized and being fed through a tube, and in people with Crohn’s disease.

Premature infants weighing less than 2,500 grams (5.5 pounds) are at risk for a life-threatening intestinal condition called necrotizing enterocolitis (NEC). In a study that pooled the results of nine randomized, placebo-controlled trials involving 1,425 infants, probiotic supplementation significantly reduced the occurrence of NEC and death associated with it. A subsequent study found similar benefits in very low-birth-weight infants weighing less than 1,500 grams (3.3 pounds).

Inflammatory bowel disease. The conditions Crohn’s
disease and ulcerative colitis are in the family of
conditions known as inflammatory bowel disease. Chronic
diarrhea is a common feature of these conditions.

A double-blind trial of 116 people with ulcerative colitis compared probiotic treatment with a relatively low dose of the standard drug mesalazine. The results suggest that probiotic treatment might be just as effective as low-dose mesalazine for controlling symptoms and maintaining remission. Evidence of benefit was seen in other trials too.

One preliminary study found S. boulardii helpful for mild diarrhea in stable Crohn’s disease. However, two studies failed to find benefit with Lactobacillus probiotics, and in an analysis of eight randomized, placebo-controlled studies, probiotics were ineffective at maintaining remission in persons with Crohn’s disease.

Probiotics might be useful for people with ulcerative colitis who have had part or all of their colon removed. Such people frequently develop a complication called pouchitis, the inflammation of part of the remaining intestine. A nine-month, double-blind trial of forty people found that a combination of three probiotic bacteria could significantly reduce the risk of a pouchitis flare-up in people with chronic pouchitis. Participants were given either placebo or a mixture of probiotics, including four strains of lactobacilli, three strains of bifidobacteria, and one strain of S. salivarius. The results showed that treated people were far less likely to have relapses of pouchitis.

Another study found that probiotics used right after surgery can help prevent pouchitis from developing. One study, however, failed to find benefit with L. johnsonii in people with Crohn’s disease who had undergone a similar operation. Finally, some evidence hints that probiotics might reduce the joint pain that commonly occurs in people with either kind of inflammatory bowel disease.

Irritable bowel syndrome. People with irritable bowel syndrome
(IBS) experience crampy digestive pain and alternating
diarrhea and constipation and other symptoms. Although the cause of IBS is not
known, one possibility is a disturbance in healthy intestinal bacteria. Based on
this theory, probiotics have been tried as a treatment for IBS, with some
success.

In a six-week, double-blind, placebo-controlled trial of 274 people with constipation-predominant IBS, the use of a probiotic formula containing B. animalis significantly reduced discomfort and increased stool frequency. Also, 266 women with constipation who consumed yogurt containing B. animalis and the prebiotic fructo-oligosaccharides twice daily for two weeks experienced significant improvement compared with women consuming regular yogurt as a placebo. Finally, in another trial of 298 persons with IBS, eight weeks of treatment with beneficial E. coli reduced typical symptoms compared with placebo.

Benefits were seen in eight other small, double-blind trials too, using L. plantarum, L. acidophilus, L. rhamnosus, L. salivarius, and Bifidobacterium, and using proprietary probiotic combinations of various strains. Benefits have also been seen with combination prebiotic and probiotic formulas and prebiotics alone. Other studies have failed to find probiotics more effective than placebo.

Two studies that pooled previous randomized trials on the use of probiotics for IBS came to similar conclusions: Probiotics appear to offer some benefit, most notably for global symptoms and abdominal discomfort. However, these two studies were unable to determine what probiotic species were most effective.

Eczema. The use of probiotics during pregnancy and after childbirth may reduce the risk of childhood eczema. In a large, long-term, double-blind study, 1,223 pregnant women were given either placebo or a probiotic mixture (containing lactobacilli and bifidobacteria) beginning two to four weeks before delivery. Their newborn children then received either probiotics or placebo for six months. The results showed that the probiotics mixture markedly reduced the incidence of eczema (though not of other allergic diseases). However, in a follow-up to this study, researchers found that the probiotic supplementation was not associated with reduced eczema in children followed through the age of five years. The probiotics also had no effect on allergic rhinitis or asthma.

Another study also yielded marginal results, and a third study involving only Lactobacillus found no benefit for the prevention of eczema. This latter study actually demonstrated a modestly increased risk of wheezing bronchitis in infants who took the probiotic. However, some probiotics combined with prebiotics may help to reduce wheezing in infants with eczema. For example, B. breve and a galacto- and fructo-oligosaccharide mixture showed benefit in one randomized study involving ninety infants.

B. longum and L. rhamnosus supplementation did not reduce the incidence of eczema atopic dermatitis or allergic sensitization at twelve months among Asian infants at risk of allergic diseases. Researchers in another study concluded that not all probiotics are created equal. In this placebo-controlled study, L. rhamnosus reduced the incidence of eczema in the children, but a strain of B. animalis did not.

According to some studies, infants who already have eczema may benefit from probiotics. However, a careful review of twelve studies involving 781 children found no convincing evidence that probiotics can effectively treat eczema in this age group.

If probiotics are beneficial for childhood eczema, they are probably more effective at preventing the condition than at treating it. A carefully conducted review of numerous studies cautiously concluded that probiotics may help reduce the risk of eczema in infants and children, particularly those at high risk. Also, two subsequent reviews found that probiotics were more effective at preventing childhood eczema, particularly when given before birth to the pregnant woman and the fetus.

Immunity. A number of studies suggest that various probiotics can enhance immune function. One twelve-week, double-blind, placebo-controlled trial evaluated twenty-five healthy elderly people, half of whom were given milk containing a particular strain of B. lactis and the other half of whom were given milk alone. The results showed various changes in immune parameters, which the researchers took as possibly indicating improved immune function. Another double-blind, placebo-controlled study of fifty people using B. lactis had similar results.

A seven-month, double-blind, placebo-controlled study of 571 children in day care centers in Finland found that the use of milk fortified with Lactobacillus GG reduced the number and severity of respiratory infections. In another controlled trial, probiotics (L. rhamnosus GG and B. lactis Bb-12) given daily to infants in their formula significantly reduced the risk of acute otitis media and of recurrent respiratory infections during the first year of life, compared with placebo.

Benefits were seen in three other large studies, in which probiotics combined with multivitamins and multiminerals helped prevent colds (or helped reduce their duration and severity) in adults. However, a smaller and shorter study failed to find any effect on respiratory infections. Similarly, L. fermentum given to twenty healthy, elite distance runners for four months during winter training was significantly more effective at reducing the number and severity of respiratory symptoms compared with placebo. One study found that Lactobacillus GG or L. acidophilus may improve the immune response to vaccinations.

Cholesterol. An eight-week, double-blind, placebo-controlled trial of seventy overweight people found that a probiotic treatment containing S. thermophilus and Enterococcus faecium could reduce LDL (bad) cholesterol by about 8 percent. Similarly positive results were seen in other short-term trials of various probiotics. However, a six-month, double-blind, placebo-controlled trial found no long-term benefit. Researchers speculate that participants stopped using the product regularly in the later parts of the study.

Safety Issues

Probiotics may occasionally cause a temporary increase in digestive gas. However, beyond that, they do not present any known risks for most people. In one trial of 140 healthy infants, formula supplemented with long-chain polyunsaturated fatty acids and probiotics appeared as safe as standard formula and did not have any effect on infant growth by the end of the seven-month trial.

However, persons who are immunosuppressed could conceivably be at risk for developing a dangerous infection with the probiotic organism itself; at least one person taking immunosuppressive medications has died in this manner.

In a detailed review of four studies, researchers concluded that the use of probiotics did not benefit persons with severe acute pancreatitis. Furthermore, according to one study, the use of probiotics led to an increased risk of mortality in persons with severe acute pancreatitis and should, therefore, be avoided under these circumstances.

Drug interactions. It may be beneficial for persons taking antibiotics to take probiotic supplements at the same time and to continue the probiotics for a couple of weeks after finishing the course of drug treatment. Doing so will help restore the balance of natural bacteria in the digestive tract.

Bibliography

Do, V. T., B. G. Baird, and D. R. Kockler. “Probiotics for Maintaining Remission of Ulcerative Colitis in Adults.” Annals of Pharmacotherapy 44 (2010): 565–71. Print.

Gao, X. W., et al. “Dose-Response Efficacy of a Proprietary Probiotic Formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for Antibiotic-Associated Diarrhea and Clostridium difficile-Associated Diarrhea Prophylaxis in Adult Patients.” American Journal of Gastroenterology 105 (2010): 1636–41. Print.

Gibson, R. A., et al. “Safety of Supplementing Infant Formula with Long-Chain Polyunsaturated Fatty Acids and Bifidobacterium lactis in Term Infants.” British Journal of Nutrition 101 (2009): 1706–13. Print.

Kim, J. Y., et al. “Effect of Probiotic Mix (Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus acidophilus) in the Primary Prevention of Eczema.” Pediatric Allergy and Immunology 21 (2010): 386–93. Print.

McFarland, L. V., and S. Dublin. “Meta-analysis of Probiotics for the Treatment of Irritable Bowel Syndrome.” World Journal of Gastroenterology 14 (2008): 2650–61. Print.

Misra, S., T. K. Sabui, and N. K. Pal. “A Randomized Controlled Trial to Evaluate the Efficacy of Lactobacillus GG in Infantile Diarrhea.” Journal of Pediatrics 155 (2009): 129–32. Print.

Park, S. K., et al. “The Effect of Probiotics on Helicobacter pylori Eradication.” Hepatogastroenterology 54 (2007): 2032–36.

Pillai, A., et al. “Probiotics for Treatment of Clostridium difficile-Associated Colitis in Adults.” Cochrane Database of Systematic Reviews (2008): CD004611. EBSCO DynaMed Systematic Literature Surveillance. Web. 28 Jan. 2016.

Rautava, S., S. Salminen, and E. Isolauri. “Specific Probiotics in Reducing the Risk of Acute Infections in Infancy.” British Journal of Nutrition 101 (2009): 1722–26. Print.

Sanders, Mary Ellen. “Beyond Rx: OTC Corner. Probiotics In Clinical Practice.” Clinical Advisor 18.10 (2015): 112–16. CINAHL Complete. Web. 28 Jan. 2016.

Tubelius, P., et al. “Increasing Work-Place Healthiness with the Probiotic Lactobacillus reuteri.” Environmental Health 4 (2005): 25. Print.

Underwood, M. A., et al. “A Randomized Placebo-Controlled Comparison of Two Prebiotic/Probiotic Combinations in Preterm Infants: Impact on Weight Gain, Intestinal Microbiota, and Fecal Short-Chain Fatty Acids.” Journal of Pediatric Gastroenterology and Nutrition 48 (2009): 216–25. Print.

Woo, S. I., et al. “Effect of Lactobacillus sakei Supplementation in Children with Atopic Eczema-Dermatitis Syndrome.” Annals of Allergy, Asthma, and Immunology 104 (2010): 343–48. Print.

Ya, W., C. Reifer, and L. E. Miller. “Efficacy of Vaginal Probiotic Capsules for Recurrent Bacterial Vaginosis.” American Journal of Obstetrics and Gynecology 203 (2010): 120. Print.

What is organ donation? |

Organ donation is a medical process in which tissue or an organ from a living or dead individual is transplanted to another individual. Advancements in modern medicine have made it possible to transplant a variety of organs and tissues, including the heart, lungs, liver, kidneys, intestines, pancreas, eyes, skin, bone, and tendons. Some organs, or parts of organs, can be transplanted from living hosts, while many other transplanted organs are obtained from recently deceased bodies.

The United States uses an "opt-in" system for organ donation in which individuals must explicitly volunteer to allow their organs to be donated after death, while other nations use an "opt-out" system in which all individuals are considered organ donors unless they explicitly state that they do not wish their organs to be donated. Individuals who wish to become living donors or to donate organs and/or tissues after death can register this preference with state agencies and with a variety of private medical organizations that link donors with medical institutions and potential recipients.

Brief History

Organ and tissue transplantation is the process of harvesting organs or tissues from the body of one individual and medically transplanting the tissues into the body of another individual. Transplanted organs can be used to help patients whose organs have been damaged due to injury or disease. American plastic surgeon Dr. Joseph Murray conducted the first organ transplantation in 1954—a kidney transplanted between identical twins—and later won the Nobel Prize in medicine for his discovery. Since the 1960s, advances in surgical techniques and technology have made it possible to transplant a variety of different types of tissue, including the heart, lungs, liver, kidneys, bones, veins and arteries, skin, and eyes.

The human body has a tendency to reject tissue transplanted from another body, owing to the immune system, which identifies the foreign tissue as a potentially harmful agent. To combat this, scientists have developed what are called "anti-rejection" medicines that lower the immune system response and allow the patient’s body to more readily adjust to the presence of foreign tissue. To reduce the risk of rejection, physicians use factors such as blood type and the presence or absence of certain types of immune system proteins to match organs and tissues with potential hosts.

Organs can be taken from living bodies or from the bodies of the recently deceased. Living donors can donate parts of organs like the liver, pancreas, skin, intestines, or a lobe of a healthy lung. The most common living donation is the kidney , because a healthy individual with two functional kidneys can donate one kidney without serious risk to their health. Living donation is often more successful than donations from deceased individuals, because the tissue is active and healthy at the time of transplantation.

Organs and tissues can also be taken from dead bodies, though this process is time-sensitive, because organs will begin to decay and lose viability for transplantation as soon as death occurs. As the time between death and transplantation is sensitive, transplantation science depends on the ability to quickly harvest and transport organs from deceased individuals.

Organ Donation in the United States

As of 2015, the United States utilizes an "opt-in" system in which individuals must consent to donate organs after their death. In some cases, an individual’s immediate family can consent to donate the deceased individual’s organs. The United States has the fourth highest organ donation rate in the world (26 donors per million individuals), and it is the leader in transplantation operations, with more transplants performed annually than in any other nation.

The laws involving organ donation and the procedure for registering as a potential organ donor differ between states. The US Department of Health and Human Services provides links through their website to help individuals determine the relevant authorities in each state to help them register as an organ donor. A number of states have integrated organ donation with driver’s and nondriver’s licensing procedures. For instance, in the state of Pennsylvania, individuals obtaining official state identification can give consent to donate organs or tissues and the label "organ donor" will be printed on the front of the state-issued identification card.

Spain is the global leader in organ donation, with every 35.3 per 1 million people listed as an organ donor. Unlike the United States, Spain has an "opt-out" policy, in which every individual is considered an organ donor unless they specifically choose to opt out of the system. Creating an opt-out system thus creates a larger pool of potential donors and eliminates situations where an individual might have chosen to donate an organ or tissue but died before having the chance to opt in to the system. However, opt-out systems are controversial, because some feel that organ donation is a personal decision and that individuals should not need to decline in order to control the use of their body tissues.

Need for Donation

In most countries, the number of patients waiting for organ donation far exceeds the number of potential and available donors. In the United States, a new patient is added to state organ transplant lists every ten minutes, and an average of seventy-nine people receive an organ transplant each day. In addition, an average of twenty-one people die each day while on the organ donation waiting list because of the scarcity of available organs. The US Department of Health and Human Services estimates in 2015 that more than 123,300 patients are waiting for an organ.

A recent controversy involves the potential for using social media and social capital to find organ donors. In 2015, thirty-nine-year-old Belgian car salesman Roel Marien posted a message on Facebook asking for a living kidney donor. Marien found eight willing donors, but Belgian physicians refused to perform the operation on the basis that it was unfair to award organs to individuals who were more "attractive" or skilled with social media, especially given that over one thousand individuals were already waiting on the Belgian transplant lists.

In the United States, there are no restrictions prohibiting individuals from using social media or other alternative methods to search for potential living donors. In 2012, Facebook adopted a feature that allowed users to add their organ donor status to their public profile and provided a link to donor registry sites. The introduction of the feature resulted in a significant increase in the number of people registered as organ donors, inspiring organ donor organizations to begin using social media to attract potential donors and to match donors and recipients. Critics of using this method argue that allowing public petitions for donors could lead to a situation in which individuals are tempted or engage in "organ trading" or "purchasing organs" from potential donors.

Bibliography

"About Organ Donation and Allocation." UCSD. Regents of the University of California, 2015. Web. 24 May 2015.

Duerr, Benjamin. "Should Patients Be Able to Find Organ Donors on Facebook?" Atlantic. Atlantic Monthly Group, 15 Apr. 2015. Web. 25 May 2015.

"History of Human Organ Transplant." Harvard Apparatus. Harvard Apparatus Regenerative Technology, 2014. Web. 24 May 2015.

Lamas, Daniela. "To Donate Your Kidney, Click Here." New Yorker. Condé Nast, 25 Sept. 2013. Web. 25 May 2015.

"Living Donation." Transplant Living. United Network for Organ Sharing, 2015. Web. 25 May 2015.

Lupkin, Sydney. "Organ Donation Rates: How the US Stacks Up." ABC News. ABC News, 18 June 2013. Web. 24 May 2015.

"Presumed Consent Not Answer to Solving Organ Shortage in US, Researchers Say." HopkinsMedicine. Johns Hopkins U, 29 Nov. 2011. Web. 29 May 2015.

"Organ Donation." Donate Life. Donate Life America, 2015. Web. 24 May 2015.

"The Need Is Real: Data." Organ Donor. US Dept. of Health and Human Services, 2015. Web. 25 May 2015.

What is xenotransplantation? |

Indications and Procedures

The transplantation of organs from human donors to human recipients has been established practice in medicine since the first successful kidney transplant was performed in 1954. Its applications have been limited, however, for two major reasons. First, the demand for human-donated organs always exceeds the supply. Second, the human body naturally rejects transplants. When the immune system recognizes compounds on the surfaces of cells from any source that is “not self,” a chain reaction begins. Antibodies attack foreign proteins and mark them for destruction by white blood cells. Enzymes attack the walls of blood vessels in a transplanted organ, destroying it within hours. To prevent rejection, transplant recipients must take immunosuppressive drugs for months or years. Blocking their immune response, however, makes transplant patients susceptible to infections, some of which can be deadly.

Xenotransplantation—the transfer of cells, tissues, or organs from nonhuman animal donors to human recipients for therapeutic purposes—might solve both of these problems. A large supply of organs can, in theory, be farmed in animals such as pigs. Also, theoretically, organs can be tailor-made to prevent rejection. Genetic engineering
techniques should be able to replace animal proteins and sugars on the surfaces of cells with human ones, thus creating an organ that the recipient’s immune system is tricked into accepting as “self.”

This genetic engineering is accomplished by transferring genes from humans to animals specially bred and farmed to serve as organ donors. To achieve this, a fertilized egg is removed from the uterus of a female donor animal. Next, human protein-coding genes are inserted into the nucleus of the fertilized egg. Finally, the egg is returned to the animal’s uterus and allowed to develop normally. If the human genetic material is preserved and activated, then the cells of the animal that develops from the egg will manufacture human proteins on the surfaces of its cells.

Uses and Complications

One concern about xenotransplantation is that new diseases might be introduced into humans from other animals. All animals carry endogenous viruses
that are part of their genetic makeup. Endogenous viruses are harmless in their natural hosts, but they can prove deadly when they cross from one species to another. For example, the Hong Kong flu virus lay harmlessly in waterbirds for many years. It then struck chickens and caused massive deaths on poultry farms, and now it infects and sometimes kills people. How the virus migrated to humans remains unknown. Also, diseases can be minor in some animals but major in humans. The herpesvirus B is one example. It gives monkeys mild cold sores but causes fatal encephalitis in people. The concern is that a virus imported into the human population through xenotransplantation might subsequently spread through other means, such as blood, air, water, or
food.

Issues of morality, ethics, and religion also arise. Although the genetic makeup of other primates most closely matches that of humans, many people believe that using apes and monkeys as organ donors would be morally unacceptable. One answer to such objections is to use animals that are routinely raised and slaughtered for food. Pigs are easy to breed and care for, and they produce large litters. Their size and weight are similar to humans. Few people object to killing pigs. Much xenotransplantation research involves the development of pigs as potential organ donors. If pig cells can be induced to display human proteins on their surfaces, then the human body will, in theory, accept organs donated from them.

Animals used as transplant donors could not come from ordinary farms because the possibility of transferring infections would be too great. The animals would need to be raised in germ-free medical facilities. Animal rights advocates condemn organ farms as cruel. Despite such objections, public opinion supports further research on xenotransplantation. In a 1998 survey sponsored by the National Kidney Foundation, nearly two-thirds of respondents judged xenotransplantation an acceptable alternative to human donor transplants.

Perspective and Prospects

Xenotransplantation is not a new idea. In 1906, with no knowledge of the immune system, French surgeon Mathieu Jaboulay transplanted a kidney from a pig and a liver from a goat to human patients, both of whom died. In 1964, Thomas Starzl at the University of Pittsburgh transplanted baboon kidneys into two humans. Both patients died from infections accompanied by kidney failure. That same year, a chimpanzee-to-human transplant fared a little better. The patient lived for nine months before the kidney failed.

In 1984, a child the press called “Baby Fae” was born prematurely with a severely malformed heart. She could not live long without a transplant. No human heart small enough was available, so surgeons at Loma Linda University in California gave Baby Fae the heart of a baboon. The operation went well, but Fae died of organ rejection and infection after the surgery.

In 1992, two liver transplants from baboons were attempted. The livers functioned well, but the patients died from infections. That same year, two women received livers from pigs. The transplants were not meant to be permanent but were intended as “bridges” until human donors could be found. In both women, the livers functioned well, but one woman died before a human organ could be located.

In 1995, British scientists succeeded in transplanting pig hearts into monkeys. Half the monkeys survived for forty days, but long-term survival was not achieved, and attempts to transplant whole organs declined after that. Instead, researchers turned to cell transplants. Since 1995, brain cells from pigs have been used with some success in the experimental treatment of people with Parkinson’s disease. In 2002, researchers in Virginia announced that they had successfully bred pigs lacking a specific sugar molecule on their cell surfaces known to trigger the rejection response in humans. Xenotransplantation advocates hope that this and similar developments will spur further progress in the field.

Bibliography

Brynie, Faith Hickman. 101 Questions About Your Immune System You Felt Defenseless to Answer . . . Until Now. Brookfield, Conn.: Twenty-first Century Books, 2000.

Cooper, David K. C., and Robert P. Lanza. Xeno: The Promise of Transplanting Animal Organs into Humans. New York: Oxford University Press, 2003.

Fovargue, Sara. Xenotransplantation and Risk: Regulating a Developing Biotechnology. New York: Cambridge University Press, 2012.

Munson, Ronald. Raising the Dead: Organ Transplants, Ethics, and Society. New York: Oxford University Press, 2004.

"Organ Transplantation." MedlinePlus, May 23, 2013.

Schicktanz, Silke, et al. Teaching Ethics in Organ Transplantation and Tissue Donation. Akron, Ohio: University of Akron Press, 2011.

Tramper, Johannes, and Yang Zhu. Modern Biotechnology: Panacea or New Pandora's Box? Wageningen, the Netherlands: Wageningen Academic Publishers, 2011.

"Xenotransplantation." US Food and Drug Administration, Feb. 4, 2010.

What is cancer staging? |

Cancers diagnosed or treated: Essentially all solid tumor cancer
diagnoses are staged similarly. Nonlocalized leukemias are staged in unique ways
according to the specific diagnosis. The diagnostic processes used to stage a
specific case vary somewhat according to cancer type and location.

Why performed: Cancer staging plays an integral role in determining overall disease prognosis as well as influencing treatment modality choices. Stage assessment also plays an important role in assuring effective communication among the patient’s medical team and accurate disease surveillance and epidemiology efforts.

Patient preparation: Patient preparation will vary according to the
technique, or supporting procedures, used to help stage the cancer. These
procedures range from physical examination and imaging X-rays, ultrasounds,
computed tomography (CT), magnetic resonance imaging (MRI) scans to laboratory
tests, biopsies, and surgical excisions with subsequent pathological examination
of the tumor. Any preparation normally required of these supporting procedures
will apply to the process.

Types of staging: There are four different types of cancer staging:
clinical staging, pathological staging, post-therapy staging, and restaging.
Clinical staging is accomplished by nonpathologic means based on physical
examination and imaging technology such as X-ray, MRI, and CT, as well as
immunologic and molecular blood tests to detect and measure cancer markers where
applicable.

Pathological staging is accomplished following tissue removal by biopsy in
which surgical tumor excision is assessed as a sound treatment option. The
biopsied tissue and/or removed tumor, surrounding tissue, and nearby lymph nodes
are examined microscopically and histologically to determine the type and extent
of the cancer from a pathologic perspective. Because treatment considerations and
survival statistics are based on the stage of a patient’s cancer, the initial
stage assessment remains static throughout the course of the disease regardless of
progression and/or response to treatment.

Post-therapy staging is completed after the patient receives an initial treatment
such as chemotherapy, hormone therapy, or radiation therapy prior to surgery or in
cases where surgery is not performed. Post-therapy staging is assessed using
clinical staging guidelines.

Should a cancer patient enter remission but subsequently present with a
recurrence, restaging may be accomplished if additional treatment is planned. The
restaging process is identical to the original one, including both clinical and
pathological staging, but is now designated with a lowercase r.
For example, a restaged Stage IV grouping would be recorded as Stage rIV.

In order to maintain terminology consistency, a limited number of
classification systems are utilized, and efforts toward additional interpretive
continuity are ongoing. Although the type of cancer dictates which specific
categorization is applied, common elements include tumor location, size and
number, lymph node involvement, and degree of metastasis
(spread). The most prevalent systems used include tumor-node-metastasis (TNM)
staging and overall group staging.

The tumor-node-metastasis (TNM) classification is adapted by the American Joint
Committee on Cancer (AJCC) and the Union for International Cancer Control.

The category T, for tumor, provides information about the original tumor such as measurement (in millimeters, centimeters) at the site of origin and its degree of invasion into nearby tissues and organs.

• TX: Cannot be measured/evaluated





• T0: No evidence of primary tumor





• Tis: In situ tumor (tumor limited to cell layers of the original site)

Beyond Tis, numerical tumor categorization offers a relative degree of
severity, with higher numbers reflecting a larger tumor and/or more aggressive
invasion.

• T1: Smaller tumor, least aggressive





• T2





• T3





• T4: Larger tumor, most aggressive

The tumor grade is the degree of abnormality (amount of differentiation from normal cells) and is determined pathologically by microscopic analysis. Typically, well-differentiated, or low-grade, tumors are considered the least aggressive and are associated with the best outcomes overall.

• GX: Cannot be determined





• G1: Tumor cells well differentiated from surrounding tissue





• G2: Tumor cells moderately well differentiated from surrounding tissue





• G3: Tumor cells poorly differentiated from surrounding tissue





• G4: Tumor cells undifferentiated from surrounding tissue

Special cases are prostate cancer and central nervous system (CNS) cancers. The most common approach to classification of prostate cancer is the Gleason system, which is based on the degree of glandular change, including size, shape, and pathologic differentiation. The Gleason Score or Sum (GS) represents the sum of the primary and secondary grade of the prostate tumor. Based on a ranking from G2 (least aggressive, best prognosis) to G10 (most aggressive, poorest prognosis), the higher the sum is, the more severe is the disease. There are several, similar classification systems used to grade CNS/brain cancers: World Health Organization (WHO), Kernohan, or Ringertz. Rather than tumor size, grading is based on tissue differentiation and degree of vascularity and necrosis. Classification is made based on a three- or four-grade system, with the higher number associated with more aggressive cancer.

The category N, for node, describes the degree that lymph nodes have been affected by cancer. This is typically accomplished by a process termed “sentinal node biopsy.” The (nearby) sentinal node or nodes are detected by injection of a radioactive or colored dye solution at the tumor site. The indicator solution will travel a path within the lymph system that circulating cancer cells would be expected to follow. The area is then scanned to detect the presence of the indicator solution in nearby, or sentinal, lymph nodes. One or more lymph nodes are then removed and examined pathologically for the presence of cancer cells. Positive findings will typically result in further removal and testing of nearby lymph nodes to determine extent.

• NX: Cannot be measured/evaluated





• N0: Nearby lymph nodes are clear of cancer

Beyond N0, numerical categorization describes the size, location, and number of lymph nodes affected. The higher the number, the more lymph nodes are involved.

• N1: One to two lymph nodes affected





• N2: Three to six lymph nodes affected





• N3: Seven or more lymph nodes affected

The M category, for metastasis, describes the degree to which the primary tumor has spread (metastasized) into surrounding tissues and/or organs.

• M0: No cancer metastasis detected





• M1: Cancer metastasis detected

Although the TNM metrics are relatively universal, each cancer type has a customized version of this classification system. In some instances, there may be many additional subcategories to refine tumor classification and offer additional prognostic information to the provider. In other cases, the staging classification may be simplified by means of truncated categorization.

Based on the established TNM categories, an overall cancer group stage is determined. Although criteria for stage assignment varies somewhat according to cancer type, the following provides a top-level overview of stage groupings:

• Stage 0: Carcinoma in situ (cancer is limited to the site of origin)

Stages I through III classify cancer where higher numbers indicate more extensive and aggressive disease. Some cancers types utilize subcategories in staging to provide more specific information about type, behavior, and prognosis.

• Stage IV: Distant metastatic cancer (cancer has spread to another, distant organ)

Special cases are female reproductive cancers, Hodgkin disease/lymphoma, colorectal cancer, and
leukemia. Female reproductive cancers are stage according to the International
Federation of Gynecologists and Obstetricians (FIGO). Although FIGO staging
classification guidelines generally follow the general TNM/group staging approach,
many of the female reproductive cancers, including those of the ovary, breast,
cervix, and uterus, are subclassified in great detail.

Hodgkin disease and other cancers of the lymphoid system are staged using the Ann Arbor classification system. Stages I through IV are defined by the anatomical location of affected lymph nodes. The higher the stage number, the more lymph nodes are affected and the more aggressive is the disease. Each stage assignment is then subclassified as either “A” (asymptomatic) or “B” (symptomatic).

Colorectal cancer uses the Dukes’ staging classification, an older
system that corresponds closely to group staging. Dukes’ A through D colorectal
cancer stages effectively translate to group Stages I through IV.

Because leukemia involves the bone marrow and has often affected many organs, including the liver, spleen, and lymph nodes, staging is based primarily on the patient’s survival outlook according to disease progression. Although not all forms of leukemia utilize a formal staging system, each form that does has a dedicated staging classification system. For example, chronic myelogenous leukemia (CML) is classified into three phases (as opposed to stages):

• Chronic: Fewer than 5 percent immature cells in circulation/bone marrow; mildly symptomatic, readily responsive to treatment





• Accelerated: 5 to 30 percent immature cells in circulation/bone marrow; more symptomatic, less responsive to treatment





• Acute/blast phase: Less than 30 percent immature cells in circulation/bone marrow; very aggressive, acute disease

Additional staging classifications, such as Rai (Stages 0-IV; U.S. predominant) and Binet (Stages A, B, and C; European predominant), are used for chronic lymphocytic leukemia (CLL). Still other systems are applied to different leukemia types such as the Stage 1 through Stage 3 classification based on level of anemia and spleen size for hairy cell leukemia (HCL).

In addition to providing information on the size, extent, and prognostic status of each cancer case, staging plays a vital role in epidemiology and treatment studies. The National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program and other cancer registries such as the National Program of Cancer Registries (NPCR) use summary staging classification in their surveillance and epidemiology efforts. For these purposes, all cancers are grouped into one of the following five summary categories:

• In situ: Early-stage cancer, present only in the cell layers where first detected





• Localized: Cancer localized to tissue/organ where first detected; no evidence of metastasis





• Regional: Cancer metastasized to nearby lymph nodes, tissues, organs





• Distant: Cancer metastasized to distant lymph nodes, tissues, organs





• Unknown: Insufficient data available to classify

Data collected are made available to clinical and research professionals so that they may better understand and address the cancer burden according to a variety of demographics and metrics, including cancer stage.

Results: Cancer staging is a vital component of the diagnostic
process. Accurate stage assessment will guide the medical team in making optimal
treatment recommendations for patient care according to prognostic expectations.
Because the epidemiologic value of the original stage is significant, the
classification remains constant throughout the course of disease. Restaging occurs
only if treatment is planned following a recurrence.

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What is Krabbé disease? |

Risk Factors

KD is an autosomal recessive disorder, occurring in approximately 1 out of every 100,000 births. It can be inherited only if both parents carry the defective gene. In every pregnancy, the risk of a baby inheriting both genes and being affected is 25 percent, and its risk of inheriting one gene and being a carrier is 50 percent. Genetic carrier testing is available for at-risk populations (Swedish or Ashkenazi Jewish) and families with a history of KD.

Etiology and Genetics

KD is one of the leukodystrophies, a group of inherited metabolic diseases causing demyelination of the central nervous system (CNS) and peripheral nervous system (PNS) and abnormal development of white matter in the brain. Each disorder has a separate gene abnormality that causes a different enzyme deficiency, resulting in a range of dysfunctions.

KD is caused by mutations of the GALC gene, resulting in a deficiency of galactocerebrosidase, a lysosomal enzyme needed to metabolize the sphingolipids galactosylceremide and galactosylsphingosine (psychosine). Galactosylceramide is found in nervous tissue and is a major constituent of CNS myelin-forming oligodendrocyte cells. (PNS myelin is made by Swann cells.) Psychosine is a lysolipid known to cause death in cells. Failure of the GALC enzyme to break down these two substrates causes demyelination of the myelin sheath and formation of large multinucleate globoid cells containing undegraded psychosine. The stored psychosine becomes toxic, inducing cell death in oligodendrocytes and thus preventing myelin from forming.

The myelin sheath is a fatty covering surrounding axons in the CNS and PNS and acts as an electrical insulator, allowing impulses to be transmitted quickly along the nerve cells. Without myelin, impulses leak out and nerves cannot function normally. Myelination is a step-by-step, ordered process that begins at about five months of gestation and continues until a child is two to three years old. In KD, this process becomes reversed, with myelin being progressively lost instead of gained. Infantile KD pathology is severe, with demyelination rapidly progressing until nearly all myelin and myelin-forming cells have disappeared.

The GALC gene is located on the long arm of chromosome 14 (14q24.3-q32.1) and is about 60 kilobases in size, consisting of 17 exons, 16 introns, and a 5 flanking region populated with GC sequences. Inhibitory sequences, plus a suboptimal nucleotide at position +4, may contribute to deficiency of the GALC protein.

More than seventy disease-causing mutations have been reported; many have been studied in the GALC protein-deficient twitcher mouse, the animal model used for Krabbé disease in humans. Alleles causing infantile KD are thought to have a large deletion, plus a point mutation involving a transition at nucleotide 502 (C502T) cDNA. Another mutation, a guanine-to-adenine substitution at nucleotide 809 (809GA), has been associated with late-onset KD.

Symptoms

Infantile KD is characterized by quickly progressing neurological dysfunction, leading to death by early childhood. In stage 1, infants experience excessive crying and irritability, stiffness, motor and mental delays and loss of already-learned skills, feeding problems, and occasionally seizures. In stage 2, babies exhibit extreme arching of the back, jerking motions of limbs, and further deterioration of mental and motor skills, and they require tube feeding. In stage 3, children lose nearly all motor and mental functions, become blind and deaf, and can no longer move or speak. Patients with the other KD phenotypes have milder, slower-progressing symptoms and longer life spans.

Screening and Diagnosis

In 2006 New York became the first state to institute universal screening for KD; Missouri did so in 2009, and Illinois in 2010.

The standard procedure for diagnosing KD is biochemical assay for GALC activity via blood sample/skin biopsy; levels at 0 to 5 percent of reference values indicate deficiency but do not distinguish infantile from other KD phenotypes. The definitive diagnosis for KD is DNA sequencing analysis of the GALC gene coding region for mutations. Pathological signs of demyelination can be detected using magnetic resonance imaging (MRI), brain MR spectroscopy, and/or diffusion tensor imaging. Other diagnostics test for cerebrospinal fluid (CSF) total protein, nerve conduction, and optic nerve damage.

Treatment and Therapy

The only available treatment for infantile KD is hematopoietic cell transplantation, using bone marrow or blood cells extracted from unrelated umbilical cord blood. However, this procedure is effective only before symptoms begin to manifest and requires a tissue match of human leukocyte antigens (HLAs) between donor and recipient. Other gene therapies have been studied in the twitcher mouse and hold promise. Treatment for this otherwise fatal disorder is symptomatic and supportive.

Prevention and Outcomes

There are no means of preventing KD, but genetic counseling/testing is available for parents who have the GLAC gene mutation. Many children with KD who have undergone transplants are living longer and fare much better neurologically, but continue to have motor and language dysfunctions.

Bibliography

Barranger, John, and Mario Cabrera-Salazar, eds. Lysosomal Storage Disorders. New York: Springer, 2007. Print.

"Krabbe Disease." Genetics Home Reference. Natl. Lib. of Medicine, Aug. 2012. Web. 31 July 2014.

Lee, W. C., et al. "Molecular Characterization of Mutations That Cause Globoid Cell Leukodystrophy and Pharmacological Rescue Using Small Molecule Chemical Chaperones." Journal of Neuroscience 30.16 (2010): 5489–497. Print.

Nyhan, William, Bruce Barshop, and Aida I. Al-Aqeel. Atlas of Inherited Metabolic Diseases. 3rd ed. London: CRC, 2011. Print.

Van der Knaap, Marjo, Jaap Valk, and Frederik Barkhof. Magnetic Resonance of Myelination and Myelin Disorders. 3rd ed. Basel: Springer, 2005. Print.