What are prions? |

Definition

The prion is an infectious agent resulting from a misfolding event in the normal PrPc prion protein (a normal cellular membrane protein found in the brain), whereby the alpha-helix structure of PrPc is transformed into a beta-sheet structure, forming PrPsc. This pathogenic (disease-causing) isomer is responsible for causing a group of rare, universally fatal neurodegenerative disorders affecting both humans and animals.

According to the International Code of Virus Classification and Nomenclature, prions are not classified as viruses but are assigned an arbitrary classification, one that seems useful to workers in particular fields. According to the International Committee of Taxonomy of Viruses, prions are classified as subviral agents/satellites.

Natural Habitat and Features

PrPc was discovered by neurologist and biochemist Stanley B. Prusiner, who won the Nobel Prize in Physiology
or Medicine in 1997 for his work in this area. He coined the term “prion” some
twenty years after researchers had proposed that an aberrant form of a host
protein could be the infectious agent in scrapie, a
long-known and fatal disease affecting sheep.

PrPc is anchored to a glycolipid linker molecule, then synthesized in the rough endoplasmic reticulum (the “cellular assembly plant”); it then crosses the Golgi apparatus (distribution organelle) and is dispersed throughout the plasma membrane onto the surface of neurons. Though most PrPc remains concentrated in lipid rafts, some is transported to pitlike areas coated with cell-adhesion cadherins, engulfed by endocytic vesicles, and then recycled. PrPc has 209 amino acids and one disulfide double bond, a alpha-helix structure at its C-terminal half, and is unstructured at its N-terminal half.

The precise functionality of PrPc is not entirely understood, although its location predisposes it to being a membrane receptor, adhesion molecule, or transporter, and to having a role in cell-to-cell communication and synaptic function. PrPc appears to be neuroprotective and is protease sensitive (receptive to enzyme breakdown).

As an isomer, PrPsc is chemically identical to its parent protein
PrPc but differs in conformation. (In inherited PrPsc, its amino acid sequencing
also differs.) Misfolding of PrPc is thought to begin in postsynaptic membranes.
On conversion, most of the alpha-helix structure of the host is lost to a large
beta-helix that forms and then converts to fibrils (lengths) of beta sheets. This
misfolded conformation, the beta-sheet model, constitutes the PrPsc molecule.

The infectious portion of the molecule, designated rPrPsc, is protease-resistant and able to form larger-order aggregates. rPrPsc is thought to propagate by polymerizing and forming amyloidlike fibrils within neurons that deposit as stable aggregates in plasma membranes, inducing conversion of more PrPc. This continuing process causes eventual death to neurons, which are overcome by accumulating aggregates and replaced with large vacuoles (holes).

PrPsc propagation and infectivity pathways are not fully elucidated, leading to
much debate over exact mechanisms. The protein-only hypothesis proposed by
Prusiner has long been held by scientists as the most plausible theory. This
hypothesis maintains that rPrPsc is both toxic and infectious because it is
insoluble and forms aggregates that interfere with nerve-cell function. The
aggregates break down to release fragments, or “seeds,” that become conformational
templates for other prion proteins to adopt. Protein misfolding cyclic
amplification, a process using in vitro purified misfolded protein, supports
Prusiner’s theory. Other interesting theories have been postulated, but the
complex nature of the prion protein and the mechanisms of its infectivity remain
elusive.

Pathogenicity and Clinical Significance

Collectively, prion diseases are a group of transmissible spongiform
encephalopathies (TSEs) that affect mammals. They are characterized by the
spongelike vacuoles (hence, the term “spongiform”) found in the cortex and
cerebellum of the brain postmortem and are the hallmark
signs of TSE disease.

Among the best-known TSEs are scrapie, bovine spongiform
encephalopathy (BSE, or mad cow disease), and
Creutzfeldt-Jacob disease (CJD). Scrapie(the
sc in PrPsc stands for “scrapie”) is transmitted by ingestion
of infected pasture or transmitted directly from sheep to lamb. Scrapie appears to
be genetic and infectious. Chronic wasting disease (CWD) is a TSE
that affects deer and elk. No incidence of scrapie or CWD being transmitted to
humans has ever been reported.

BSE acquired notoriety in the 1990’s when an outbreak occurred in the United Kingdom; up to one thousand cases were reported at its peak, leading to public outcry and political repercussions. First recognized in the 1970’s, BSE is believed to have spread from the practice of feeding cattle meat-and-bone meal, which at some point became contaminated with by-products taken from an infected animal.

A chilling consequence of the BSE outbreak was the transmission of the disease to humans. In 1996, a variant of classic CJD (called vCJD) was identified and linked to human consumption of BSE-infected beef products. The link was made because the timing of the outbreak was consistent with known incubation periods for human forms of TSE. European and U.S. authorities were especially concerned because they were unable to make predictions about disease prevalence or incidence.

Prion diseases in humans can be acquired or inherited. There are four types of CJD: sporadic (sCJD), variant (vCJD), familial (fCJD), and iatrogenic. The sporadic or classic form occurs spontaneously for no known reason, while familial is inherited. Variant is thought to be acquired by eating contaminated food, while iatrogenic is transmitted by prion-contaminated materials (such as neurosurgical instruments, tissue implants, and blood). A disease called kuru is also an acquired form of prion disease. Kuru was spread by New Guineans who practiced cannibalism until the 1950’s. Its long incubation period meant that cases were still being reported up to the 1990’s.

Inherited forms of TSE include familial CJD, Gerstmann-Sträussler-Scheinker
syndrome (GSS), and fatal familial
insomnia (FFI) and are caused by defects in the PrNP gene
encoding the prion protein. Twenty such mutations have been identified, involving
either amino acid substitutions or repeats of a twenty-four-base pair segment.

GSS is caused by mutations at codons 102, 117, or 198, and is characterized by progressive cerebellar dysfunction (worsening ataxia, motor problems, and dementia). GSS does not usually become symptomatic until the person is age forty to fifty years, and it lasts for several years before death.

FFI is caused by a mutation of asparagine for aspartate at codon 178. Patients have intractable insomnia and lack REM (rapid eye movement) sleep and have sympathetic hyperactivity and other characteristics of CJD.

Drug Susceptibility

There is no cure for TSEs and no viable treatment. Researchers have identified hundreds of potential inhibitors of PrPsc that may someday reduce infectivity or prevent the onset of disease.

Bibliography

Bosque, Patrick J., and Kenneth L. Tyler. “Prions and Prion Diseases of the Central Nervous System (Transmissible Neurodegenerative Diseases).” In Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by Gerald L. Mandell, John F. Bennett, and Raphael Dolin. 7th ed. New York: Churchill Livingstone/Elsevier, 2010. Print.

Caughey, Byron. “Prion Protein Conversions: Insight into Mechanisms, TSE Transmission Barriers, and Strains.” British Medical Bulletin 66 (2003): 109-120. Print.

Mead, Simon, Sarah Tabrizi, and John Collinge. “Prion Diseases of Humans and Animals.” In Infectious Diseases, edited by Jon Cohen, Steven Opal, and William Powderly. 3d ed. St. Louis, Mo.: Mosby/Elsevier, 2010. Print.

Prusiner, Stanley B. “The Prion Diseases.” Scientific American 272, no. 1 (January, 1995): 48-57. Print.

Prusiner, Stanley B., ed. Prion Biology and Diseases. 2d ed. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2004. Print.

Rowland, Lewis P., and Timothy A. Pedley, eds. Merritt’s Textbook of Neurology. 12th ed. Philadelphia: Lippincott Williams & Wilkins, 2010. Print.

Sadowski, Martin, Ashok Verma, and Thomas Wisniewski. “Infections of the Nervous System: Prion Diseases.” In Neurology in Clinical Practice, edited by Walter G. Bradley et al. 5th ed. Philadelphia: Butterworth Heinemann/Elsevier, 2008. Print.

What are club drugs? |

Causes and Symptoms

Club drugs are often less expensive and more accessible than other controlled substances, making them particularly attractive to young people who want to experiment with drugs at a rave, dance party, or bar with friends. This desire, combined with a false belief that club drugs are safer than other drugs, can lead people to try drugs and sometimes begin using them regularly. Club drugs are often first used at dance clubs or with friends. The belief that such drugs are natural analogs of prescription drugs or are not illegal fuels a misconception of their safety. Because the drugs are psychedelic, reactions of individual users will vary significantly depending on the user’s emotional state, concurrent use of other substances, underlying psychiatric conditions, personality, and past experience with the drugs. Additionally, because these substances are street drugs, their contents are usually subject to some variability, such as being mixed with less expensive drugs, and their quality may vary substantially.

Club drugs go by many different names. They include substances such as gamma-hydroxybutyrate (GHB, Georgia home boy, liquid X), ketamine hydrochloride (ketamine, special K), lysergic acid diethylamide (LSD, acid, blotter), methylenedioxymethamphetamine (MDMA, Adam, ecstasy, X, Molly), and Rohypnol (roofies, roach, roche). They also include herbal ecstasy (herbal X, cloud nine, herbal bliss), which is a drug made from ephedrine or pseudoephedrine and caffeine.

The effects of club drugs vary, but as a group they cause a number of positive reactions, including euphoria, feelings of well-being, emotional clarity, a decreased sense of personal boundaries, and feelings of empathy and closeness to others. However, they can also cause significant negative reactions, including panic, impaired judgment, amnesia, impaired motor control, insomnia, paranoia, irrational behavior, flashbacks, hallucinations, rapid heartbeat, high blood pressure, chills, sweating, tremors, respiratory distress, convulsions, and violence. It is not uncommon for individuals to mix these drugs with alcohol, prescription drugs, or other illegal drugs. When drugs are taken in combination, the drugs can interact and cause dangerous and unexpected reactions.

Treatment and Therapy

The effects of club drugs vary by substance and the treatment for drug abuse varies by substance as well. In general, club drugs tend to be seen more in emergency care settings than in primary health care settings. This is because some of the problems that they cause are often critical and require emergency care. For instance, overdose, strokes, allergic shock reactions, blackouts, loss of consciousness, and accidents related to these conditions may require emergency care. Similarly, dehydration and heat exhaustion can result from prolonged periods of dancing or other physical exertion, as can occur in rave situations. Date rapes have been known to occur with these drugs, particularly Rohypnol, and injuries due to sexual assault may also require emergency care.

The long-term impact of problems, such as those described above, may require psychotherapy. In addition, problems related to the abuse of or dependence upon club drugs will be addressed in much the same manner as for other substances of abuse. General addiction treatment is advised.

Perspective and Prospects

The dangers of club drugs underscore the continuing need for social awareness of these substances that may otherwise seem harmless. Just because a substance is not listed as an illegal drug does not mean that it cannot be dangerous. Any drug, whether sold over the counter, by prescription, or in any other way, can be misused and be dangerous or even fatal to the user.

While the experimental use of psychedelic substances for psychotherapeutic work may prove beneficial to certain groups of patients, such work is balanced by investigations into neurology, physiology, psychopharmacology, and psychology, which emphasize that the proposed benefits do not outweigh the risks. Continued exploration of the neuronal, developmental, social, and other health effects of using club drugs is necessary as they pose a significant danger to public health, particularly to younger populations.

Bibliography

Holland, Julie, ed. Ecstasy: The Complete Guide—A Comprehensive Look at the Risks and Benefits of MDMA. Rochester: Inner Traditions International, 2001. Print.

Jansen, Karl. Ketamine: Dreams and Realities. Ben Lomond: Multidisciplinary Association for Psychedelic Studies, 2004. Print.

Kuhn, Cynthia, Scott Swartzwelder, and Wilkie Wilson. Buzzed: The Straight Facts about the Most Used and Abused Drugs from Alcohol to Ecstasy. Rev. 4th ed. New York: Norton, 2014. Print.

O’Neill, John, and Pat O’Neill. Concerned Intervention: When Your Loved One Won’t Quit Alcohol or Drugs. Oakland: New Harbinger, 1992. Print.

Stafford, Peter. Psychedelics. Berkeley: Ronin, 2003. Print.

What is quinsy? |

Causes and Symptoms

Quinsy, also called peritonsillar abscess, is a rare disorder. Medical professionals most often diagnose the condition in young adults. Primarily after extreme tonsillitis,
bacterial infections (usually streptococci) spread from one or both tonsils to adjacent tissues, which become pus-filled. In addition to the throat, the infection may cover the palate and extend to the lungs, potentially blocking the airway.

Patients develop a fever and tender throat glands. Some people experience chills. Because swollen tonsils shift and push the uvula aside, patients often are unable to open their mouths normally, a condition known as trismus, and swallowing is painful. Patients sometimes lean their heads in the direction of the abscess. Other symptoms include swelling of facial tissues, drooling, fatigue, earache, and headache. Some patients become hoarse and have foul breath.

Quinsy is often prevented because patients with tonsillitis are administered antibiotics and are monitored to stop infections from spreading. A person who has had tonsillitis and who develops symptoms of quinsy should consult health care professionals. Sore throats that do not heal with antibiotics or that become worse alert physicians to the possibility of quinsy.

Medical professionals evaluate patients for quinsy by examining the tonsils for swelling and abnormal reddening of the mouth, throat, and chest tissues. In some cases of quinsy, the tonsils may appear normal. Samples of aspirated abscess
fluid are examined for bacteria. Ultrasound or computer imaging is used if patients cannot open their mouths.

Treatment and Therapy

Physicians are divided on the preferred treatment for quinsy. Surgical procedures involve draining pus from abscesses
through incisions or needle aspiration. Studies have shown that incision drainage is effective at stopping quinsy and that needle aspiration is more likely to result in additional abscessing. Tonsillectomy specifically for quinsy is usually advised only if no other treatments are effective. Approximately 10 to 15 percent of patients undergoing treatment experience recurring quinsy.

Emergency surgery is necessary if quinsy affects breathing. Other possible complications include pneumonia, meningitis, heart
inflammation (pericarditis), and fluid surrounding the lungs (pleural effusion). Rarely, quinsy patients develop endocarditis, a bacterial infection of the heart. Quinsy patients should seek medical care if they have chest pains, coughing, or breathing complications.

Perspective and Prospects

The word “quinsy” is based on references made by the ancient Greeks to abscessed throats. As early as the fourteenth century, medical literature included details about the peritonsillar space. The term “quinsy” was appropriated after that time to describe sore throats and tonsils. Modern physicians disproved claims that President George Washington died from quinsy, as contemporary sources had claimed. Since the 1980s, researchers have been evaluating the most effective treatments for quinsy. The Haemophilus influenzae type b vaccine, first administered in 1987, has minimized quinsy occurrence.

Bibliography

Ben-Joseph, Elana Pearl. "What Is a Peritonsillar Abscess?" TeensHealth. Nemours Foundation, May 2012.

Bluestone, Charles D., et al., eds. Pediatric Otolaryngology. 4th ed. 2 vols. Philadelphia: W. B. Saunders, 2003.

Gleeson, Michael, et al, ed. Scott-Brown’s Otolaryngology: Head and Neck Surgery. 7th ed. Boston: Butterworth-Heinemann, 2008.

Litin, Scott C., ed. Mayo Clinic Family Health Book. 4th ed. New York: HarperResource, 2009.

Neff, Deanna M., and Michael Woods. "Peritonsillar Abscess." Health Library, Mar. 15, 2013.

Schwartz, Seth, et al. "Periotonsillar Abscess." MedlinePlus, Nov. 9, 2012.

Woodson, Gayle E. Ear, Nose, and Throat Disorders in Primary Care. Philadelphia: W. B. Saunders, 2001.

What does "ni***r-lover" mean to residents of Maycomb? Why is it such a powerful insult?

One person who uses "ni***r-lover" a lot is Mrs. Dubose in chapter 11. However Cecil Jacobs, Scout's cousin Francis, and Bob Ewell also use other derivations of the insult to cause psychological and emotional harm towards others of their own race. Apparently, the social status quo for living in Maycomb seems to divide people by racial lines; so, a person who uses the N-word towards another white person intends for it to sting with intense disapproval for having crossed those lines. If a...

One person who uses "ni***r-lover" a lot is Mrs. Dubose in chapter 11. However Cecil Jacobs, Scout's cousin Francis, and Bob Ewell also use other derivations of the insult to cause psychological and emotional harm towards others of their own race. Apparently, the social status quo for living in Maycomb seems to divide people by racial lines; so, a person who uses the N-word towards another white person intends for it to sting with intense disapproval for having crossed those lines. If a white person uses the N-word towards an African American, it is used to show racial, social and political dominance. There is nothing more offensive to white people in Maycomb than to see anyone crossing those pre-determined racial lines. White people want to maintain their dominance and control over how life is governed in their town (which symbolizes every other town in the South at that time, too). As a result, they throw out different uses of the N-word to intimidate others to step back into line with their way of life. Atticus has a couple of things to say about people using these words. First, when he is talking to his brother Jack about the Tom Robinson case, he says the following:

"You know what's going to happen as well as I do, Jack, and I hope and pray I can get Jem and Scout through it without bitterness, and most of all, without catching Maycomb's usual disease. Why reasonable people go stark raving mad when anything involving a Negro comes up, is something I don't pretend to understand" (88).

Here Atticus basically says that reasonable people go crazy when those racial lines are threatened and he doesn't understand it. When Scout asks him about people calling him a "ni****-lover," like Mrs. Dubose, he tells her the following:

"Scout. . . ni****-lover is just one of those terms that don't mean anything--like snot-nose. . . ignorant, trashy people use it when they think somebody's favoring Negroes over and above themselves. It's slipped into usage with some people like ourselves, when they want a common, ugly term to label somebody. . . baby, it's never an insult to be called what somebody thinks is a bad name. It just shows you how poor that person is, it doesn't hurt you" (108).

With this passage, Atticus is trying to calm his daughter down about people verbally attacking him. The N-word is serious, but he teaches her not to take what other people say so hard because it really reflects who they are inside.

Which of the following is the strongest electrolyte based on the information provided?

An electrolyte is a substance that can dissolve in water to form a solution. The substance forms ions in the solution which can move freely and conduct electricity. Stronger electrolytes have a higher conductance and allow for an easier flow of electricity.

Equivalent conductance is the conductance of a volume of solution containing one equivalent of an electrolyte. The SI unit of equivalent conductance m^2*Siemens.

The chart gives the equivalent conductance of four electrolytes. The...

An electrolyte is a substance that can dissolve in water to form a solution. The substance forms ions in the solution which can move freely and conduct electricity. Stronger electrolytes have a higher conductance and allow for an easier flow of electricity.

Equivalent conductance is the conductance of a volume of solution containing one equivalent of an electrolyte. The SI unit of equivalent conductance m^2*Siemens.

The chart gives the equivalent conductance of four electrolytes. The equivalent conductance of NaOH is 238, for HF it is 96, for HCl it is 412 and for KOH it is 228.

From the data provided we can conclude that HCl is the strongest electrolyte of the four that are given.

What are monoclonal antibodies? |

Cancers treated: Lymphoma, leukemia, breast cancer, head and neck cancers, colorectal cancer, lung cancer

Subclasses of this group: Murine (composed entirely of mouse sequences), chimeric (composed of approximately one-third mouse and two-thirds human sequences), humanized (composed of at least 90 percent human sequences), and human (antibodies that are fully human in composition)

Delivery routes: As a result of their molecular size and susceptibility to enzymatic digestion in the gut if administered orally, monoclonal antibodies must usually be administered by intravenous (IV) infusion.

How these drugs work:
Antibodies are proteins that bind to a specific site, or epitope, on a specific target molecule. In response to infection or immunization with a foreign agent, the immune system generates many different antibodies that bind to the foreign molecules. This pool of polyclonal antibodies contains a mixture of different antibody molecules, each of which binds to a specific epitope. Isolation of a single antibody from a polyclonal antibody pool would yield a highly specific molecular tool with the ability to bind to a single epitope. Georges Köhler, César Milstein, and Niels Kaj Jerne invented the process of producing monoclonal antibodies in 1975 and shared the 1984 Nobel Prize in Physiology or Medicine for their discovery. Since then, monoclonal antibodies have become an important tool in biological research and in medicine.

The process of producing monoclonal antibodies involves fusing an individual B cell, which produces a single antibody with a single specificity but which has a finite life span, with a long-lived myeloma tumor cell. The B cell is taken from the spleen or lymph nodes of an animal that has been challenged with the antigen of interest. The combination of the B cell and the myeloma cell produces a hybridoma cell, a kind of perpetual antibody-producing factory. The hybridoma cell produces the single specific antibody and can be grown in culture indefinitely, allowing the production of large amounts of the monoclonal antibodies. Monoclonal antibodies are potentially more effective than conventional drugs in treating cancer, since conventional drugs attack not only cancer cells but also normal cells. Monoclonal antibodies attach only to the specific target molecule. Since monoclonal antibodies are specific for a particular antigen, one designed to bind to ovarian cancer cells, for instance, will not bind to colorectal cancer cells.

The first monoclonal antibodies were made from mouse B cells. When administered into humans, mouse antibodies are recognized by the human immune system as foreign (because they are from a different species) and can elicit an immune response against them, causing allergic-type reactions. Researchers have since learned how to replace some portions of the mouse antibody sequences with human antibody sequences. The application of genetic engineering techniques has allowed the production of chimeric, humanized, and, more recently, fully human monoclonal antibodies.

An antibody molecule is composed of two heavy polypeptide chains and two light polypeptide chains. Both heavy and light chains are composed of a region that varies from antibody to antibody, the variable region, and a constant region that is conserved. By combining human sequences for the constant region with murine sequences for portions of the variable region, the amount of murine sequence can be decreased. Depending on how much murine sequence is left, the result is either a chimeric (with approximately one-third murine and two-thirds human sequence) or a humanized (with at least 90 percent human sequence) monoclonal antibody. Genetically engineered mouse strains are now available that contain a large portion of human deoxyribonucleic acid (DNA) that codes for the antibody heavy and light chains, with the mouse’s own heavy and light chain genes inactivated. Using these mice to produce B cells for the construction of hybridomas allows the generation of fully human antibodies, which are likely to be safer and may be more effective than the previous generation of monoclonal antibodies.

One potential treatment for cancer involves using monoclonal antibodies that bind only to a cancer cell-specific component of interest and induce an immunological response against the target cancer cell (referred to as “naked” monoclonal antibodies). Monoclonal antibodies can also be designed for the delivery of another (nonspecific) agent, such as a toxin, radioisotope, or cytokine, to the cancer cell for the purpose of killing it (referred to as “conjugated” monoclonal antibodies).

Some naked monoclonal antibodies bind to cancer cells and exert their action by marking the cells to help the body’s immune system destroy them. Rituxan (rituximab) and Campath (alemtuzumab) are examples of this type of monoclonal antibody. Rituximab binds to the CD20 antigen, a protein found on B cells, and is used to treat B-cell non-Hodgkin lymphoma. Alemtuzumab binds to the CD52 antigen, another protein present on B and T cells, and is used to treat some patients with B-cell chronic lymphocytic leukemia.

Some naked monoclonal antibodies bind to functional parts of cancer cells or other cells that help cancer cells grow and act by interfering with the cancer cells’ ability to grow. Herceptin (trastuzumab), Erbitux (cetuximab), and Avastin (bevacizumab) are examples of this type of monoclonal antibody. Trastuzumab binds to the HER2/neu protein, a protein present in large numbers on tumor cells in some cancers that, when activated, helps these cells grow. Trastuzumab acts by inactivating these proteins. It is used to treat some breast cancers. Cetuximab binds to the epidermal growth factor receptor (EGFR) protein, which when present in high levels on cancer cells helps them grow. Cetuximab blocks the activation of EGFR and is used to treat some advanced colorectal cancers and some head and neck cancers. Bevacizumab binds to the vascular endothelial growth factor (VEGF), a protein that cancer cells produce to attract the new blood vessels they need for growth. Bevacizumab prevents VEGF from functioning and is used to treat some colorectal, lung, and breast cancers.

Some of these monoclonal antibodies have been used in cancer treatment for many years. At first they were used mainly after other treatments had failed, but as more studies have been done, the trend is to use them earlier in the course of cancer treatment.

Conjugated monoclonal antibodies (also called “tagged” or “loaded” monoclonal antibodies) are attached to anticancer (chemotherapy) drugs, toxins, or radioactive substances and used as vehicles to deliver these toxic agents directly to cancer cells. Radiolabeled monoclonal antibodies are attached to radioactive substances; treatment with such agents is called radioimmunotherapy. Chemolabeled monoclonal antibodies are attached to anticancer drugs, and immunotoxins are monoclonal antibodies attached to toxins. Zevalin (ibritumomab tiuxetan) and Bexxar (tositumomab) are examples of radiolabeled monoclonal antibodies. Both bind to an antigen on cancerous B lymphocytes and are used to treat some B cell non-Hodgkin lymphomas. Mylotarg (gentuzumab ozogamicin) is an example of an immunotoxin. It contains the toxin calicheamicin attached to a monoclonal antibody that binds to the CD33, a protein antigen present on most leukemia cells, and is used to treat some acute myelogenous leukemias.

Clinical trials of monoclonal antibody therapy are in progress for patients with almost every type of cancer. As more cancer-associated antigens have been identified and studied, it has been possible for researchers to make monoclonal antibodies against more types of cancer.

Side effects: Antibodies that contain murine sequences can be recognized by the human immune system as foreign, causing systemic inflammatory effects such as fever, chills, weakness, headaches, nausea, vomiting, and diarrhea. Some monoclonal antibodies also have side effects associated with the antigen that they target. For example, some monoclonal antibodies can affect the bone marrow’s ability to produce blood cells, which can result in an increased risk of bleeding or infection in some patients.

George, Andrew J. T., and Catherine E. Urch, eds. Diagnostic and Therapeutic Antibodies. Totowa: Humana, 2000. Print.

Guoning Li et al. "Monoclonal Antibody-Related Drugs for Cancer Therapy." Drug Discoveries and Therapeutics 7.5 (2013): 178–84. Print.

Lianos, Georgios D., et al. "Potential of Antibody-Drug Conjugates and Novel Therapeutics in Breast Cancer Management." OncoTargets and Therapy 7 (2014): 491–500. Print.

Melero, I., et al. “Immunostimulatory Monoclonal Antibodies for Cancer Therapy.” Nature Reviews Cancer 7 (2007): 95–106. Print.

Reichert, J. M., and V. E. Valge-Archer. “Development Trends for Monoclonal Antibody Cancer Therapeutics.” Nature Reviews Drug Discovery 6 (2007): 349–56. Print.

Wei-Xiang Qi et al. "Incidence and Risk of Severe Infections Associated with Anti-Epidermal Growth Factor Receptor Monoclonal Antibodies in Cancer Patients: A Systematic Review and Meta-Analysis." BMC Medicine 12.1 (2014): 1–25. Print.

Zafir-Lavie, I., Y. Michaeli, and Y. Reiter. “Novel Antibodies as Anticancer Agents.” Oncogene 28 (2007): 3714–33. Print.

What is Neal E. Miller and John Dollard's S-R theory?

Introduction

Much, if not most, human behavior is learned. How human beings learn is one of the central, and most controversial, topics in psychology. Neal E. Miller and John Dollard used principles of learning developed by Clark L. Hull, who studied how animals learn, and applied them to explain complex human behavior.

According to Miller and Dollard, human behavior occurs in response to cues. A red traffic light, for example, is a cue to stop, whereas green is a cue to go. A cue is simply any stimulus that is recognized as different from other stimuli. A cue may bring about a variety of responses, but some responses are more likely to occur than others. The response to a cue most likely to occur is called the dominant response. Responses to a cue are arranged in a response hierarchy, from the dominant response to the response least likely to occur. A person’s response hierarchy can change. The hierarchy that a person has originally is called the initial hierarchy. If the initial hierarchy is inborn, it is known as the innate hierarchy. When a hierarchy changes, the result is known as the response hierarchy.

Response Hierarchy and Learning

Change in a response hierarchy occurs as a result of learning. There are four fundamental considerations in the explanation of how learning occurs: drive, cue, response, and reinforcement.

A drive
is an intense stimulus, such as hunger, that motivates a response. The cue is the stimulus that elicits the response. If the dominant response in the hierarchy results in a reduction in the drive, then reinforcement
will occur. Reinforcement means that the association, or connection, between the cue (stimulus) and response is strengthened; the next time the cue occurs, therefore, that response will be even more likely to occur. Reinforcement occurs when a person realizes that the response has led to a reward, although such awareness is not always necessary; reinforcement can also occur automatically. In other words, Miller and Dollard’s theory states that for people to learn, they must want something (drive), must do something (response) in the presence of a distinct stimulus (cue), and must get some reward for their actions (reinforcement).

If the dominant response does not result in a reward, the chance that the dominant response will occur again is gradually lessened. This process is called extinction. Eventually, the next response in the hierarchy will occur (in other words, the person will try something else). If that response results in reward, it will be reinforced and may become the dominant response in the hierarchy. In this way, according to Miller and Dollard, humans learn and change their behavior. According to this theory, connections between stimulus and response are learned; these are called habits. Theories that view learning in this way are called stimulus-response, or S-R, theories. The total collection of a person’s habits makes up the individual’s personality.

Role of Drives

Drives, as previously noted, motivate and reinforce responses. Some drives, such as hunger, thirst, sex, and pain, are inborn and are known as primary drives. These drives are naturally aroused by certain physiological conditions; through learning, however, they may also be aroused by cues to which they are not innately connected. For example, one may feel hungry when one sees a favorite restaurant even though one has recently eaten. Drives aroused in this way (that is, by previously neutral cues) are called secondary, or learned, drives.

The natural reaction to an aversive stimulus is pain. Pain is a primary drive; it motivates a person to act, and any response that reduces pain will be reinforced. Neutral cues associated with pain may also produce a response related to pain called fear
(or anxiety). Fear motivates a person to act; a response that reduces fear will be reinforced. Fear is therefore a drive; it is a drive that is especially important for understanding neurotic behavior, according to Miller and Dollard. For example, a fear of a harmless cue such as an elevator (an elevator phobia) will motivate a person to avoid elevators, and such avoidance will be reinforced by reduction of fear.

Cue Responses

A response to one cue may also occur to cues that are physically similar to that cue; in other words, what one learns to do in one situation will occur in other, similar situations. This phenomenon is called stimulus generalization.

Many responses are instrumental responses; that is, they act on and change some aspect of the environment. Other responses are known as cue-producing responses; the cues from these responses serve to bring about other responses. Words are especially important cue-producing responses; someone says a word and another person responds, or one thinks a word and this is a cue for another word. Thinking can be considered as chains of cue-producing responses—that is, as a sequence of associated words; in this way Miller and Dollard sought to describe the higher mental processes such as thinking, reasoning, and planning.

Social Role of Learning

In their book Social Learning and Imitation (1941), Miller and Dollard pointed out that to understand human behavior, one must know not only the process of learning but also the social conditions under which learning occurs. Human learning is social—that is, it occurs in a social context, which can range from the societal level to the interpersonal level. The process of imitation is one example of how what an individual learns to do depends on the social context.

Imitation involves matching, or copying, the behavior of another person. If the matching behavior is rewarded, it will be reinforced, and the individual will therefore continue to imitate. The cue that elicits the imitating response is the person being imitated (the model), so that the imitative behavior, in Miller and Dollard’s analysis, is dependent on the presence of the model. In this way, Miller and Dollard used S-R theory to explain how individuals learn what to do from others and thereby learn how to conform to society.

Psychoanalytic Approach to Neurosis

In their best-known work, Personality and Psychotherapy: An Analysis in Terms of Learning, Thinking, and Culture (1950), Dollard and Miller applied S-R theory to explain how
neurosis is learned and how it can be treated using learning principles. They pointed out three central characteristics of neurosis that require explanation: misery, stupidity, and symptoms. The misery that neurotics experience is a result of conflict. Conflict exists when incompatible responses are elicited in an individual. An approach-approach conflict exists when a person has to choose between two desirable goals; once a choice is made, the conflict is easily resolved. An avoidance-avoidance conflict exists when an individual must choose between two undesirable goals. An approach-avoidance conflict exists when an individual is motivated both to approach and to avoid the same goal. The last two types of conflicts may be difficult to resolve and under certain conditions may result in a neurosis.

Dollard and Miller tried to explain some aspects of psychoanalytic theory in S-R terms; like Sigmund Freud, the founder of psychoanalysis, they emphasized the role of four critical childhood training situations in producing conflicts that can result in neurosis. These are the feeding situation, cleanliness training, sex training, and anger-anxiety conflicts. Unfortunate training experiences during these stages of childhood may result in emotional problems. Childhood conflicts arising from such problems may be repressed and may therefore operate unconsciously.

The “stupidity” of the neurotic is related to the fact that conflicts that produce misery are repressed and unconscious. Dollard and Miller explained the psychoanalytic concept of repression
in terms of S-R theory in the following manner. Thinking about an experience involves the use of cue-producing responses (that is, the use of words) in thinking. If no words are available to label an experience, then a person is unable to think about it—that is, the experience is unconscious. Some experiences are unconscious because they were never labeled; early childhood experiences before the development of speech and experiences for which the culture and language do not provide adequate labels are examples of experiences that are unconscious because they are unlabeled. Labeled painful experiences may also become unconscious if a person stops thinking about them. Consciously deciding to stop thinking about an unpleasant topic is called suppression. Repression is similar to suppression except that it is automatic—that is, it occurs without one consciously planning to stop thinking. For Dollard and Miller, therefore, repression is the automatic response of stopping thinking about very painful thoughts; it is reinforced by drive reduction and eventually becomes a very strong habit.

The third characteristic of neuroses requiring explanation is symptoms. Phobias, compulsions, hysteria, and alcoholism are examples of symptoms. Symptoms arise when an individual is in a state of conflict-produced misery. This misery is a result of the intense fear, and of other intense drives (for example, sexual drives), involved in conflict. Because the conflict is unconscious, the individual cannot learn that the fear is unrealistic. Some symptoms of neurosis are physiological; these are direct effects of the fear and other drives that produce the conflict. Other symptoms, such as avoidance in a phobia, are learned behaviors that reduce the fear or drives of the conflict. These symptoms are reinforced, therefore, by drive reduction.

Therapeutic Techniques

Dollard and Miller’s explanation of psychotherapy is largely a presentation of key features of psychoanalysis described in S-R terms. Therapy is viewed as a situation in which new learning can occur. Because neurotic conflict is unconscious, new learning is required to remove repression so that conflict can be resolved. One technique for doing this, taken directly from psychoanalysis, is free association; here, neurotic patients are instructed to say whatever comes to their consciousness. Because this can be a painful experience, patients may resist doing this, but, because the therapist rewards patients for free associating, they eventually continue. While free associating, patients become aware of emotions related to their unconscious conflicts and so develop a better understanding of themselves.

Another technique borrowed from psychoanalysis involves a phenomenon known as transference. Patients experience and express feelings about the therapist. Such feelings really represent, in S-R terms, emotional reactions to parents, teachers, and other important persons in the patient’s past, which, through stimulus generalization, have been transferred to the therapist. The therapist helps the patient to recognize and label these feelings and to see that they are generalized from significant persons in the patient’s past. The patient in this way learns how she or he really feels. The patient learns much about herself or himself that was previously unconscious and learns how to think more adaptively about everyday life. The patient’s symptoms are thereby alleviated.

Extending the Behaviorist Approach

The S-R theory used by Miller and Dollard had its intellectual roots in the thinking of the seventeenth century, when human beings were thought of as being complicated machines that were set in motion by external stimuli. At the beginning of the twentieth century, the stimulus-response model was adopted by John B. Watson, the founder of behaviorism. Watson used the S-R model to explain observable behavior, but he avoided applying it to mental processes because he believed that mental processes could not be studied scientifically.

Miller and Dollard extended the behaviorism of Watson to the explanation of mental events through their concept of the cue-producing response and its role in the higher mental processes. This was an S-R explanation: Mental processes were seen as arising from associations between words that represent external objects; the words are cues producing responses. Miller and Dollard’s approach, therefore, represented a significant departure from the behaviorism of Watson. Miller and Dollard tried to explain mental events in their book Personality and Psychotherapy, in which they attempted to explain many psychoanalytic concepts in S-R terms. Because psychoanalysis is largely a theory of the mind, it would have been impossible for them not to have attempted to describe mental processes.

Contributions to Mental Processes Research

The approach to explaining mental processes used by Miller and Dollard, though it represented a theoretical advance in the 1950s, was gradually replaced by other explanations beginning in the 1960s. The drive-reduction theory of learning that they advocated came under criticism, and the S-R view that humans passively react to external stimuli was criticized by many psychologists. As a result, new theories of learning emphasizing cognitive (mental) concepts were developed.

New ways of thinking about mental processes were also suggested by fields outside psychology; one of these was computer science. The computer and its program were seen as analogous to human mental processes, which, like computer programs, involve the input, storage, and retrieval of information. The computer and its program, therefore, suggested new ways of thinking about the human mind. Miller and Dollard’s S-R theory has largely been replaced by concepts of contemporary cognitive science.

Miller and Dollard’s theory still exercises an important influence on contemporary thinking in psychology. Their analysis of psychoanalysis in terms of learning theory made the important point that neuroses could be unlearned using the principles of learning. Behaviorally oriented treatments of emotional disorders owe a debt to the intellectual legacy of Miller and Dollard.

Bibliography

Bouton, Mark E. Learning and Behavior: A Contemporary Synthesis. Sunderland: Sinauer, 2007. Print.

Dollard, John, et al. Frustration and Aggression. 1939. London: Routledge, 1998. Print.

Dollard, John, and Neal E. Miller. Personality and Psychotherapy: An Analysis in Terms of Learning, Thinking, and Culture. New York: McGraw-Hill, 1950. Print.

Hall, Calvin S., Gardner Lindzey, and John B. Campbell. Theories of Personality. 4th ed. New York: Wiley, 1998. Print.

Klein, Stephen B. Learning: Principles and Applications. 6th ed. Thousand Oaks: Sage, 2012. Print.

Merriam, Sharan B., Rosemary S. Caffarella, and Lisa M. Baumgartner. Learning in Adulthood: A Comprehensive Guide. 3rd ed. San Francisco: Jossey-Bass, 2007. Print.

Miller, Neal E. “Studies of Fear as an Acquirable Drive: I. Fear as a Motivator and Fear-Reduction as Reinforcement in the Learning of New Responses.” Journal of Experimental Psychology 38 (1948): 89–101. Print.

Miller, Neal E., and John Dollard. Social Learning and Imitation. 1941. Westport: Greenwood, 1979. Print.

Pear, Joseph J. The Science of Learning. New York: Psychology, 2014. Digital file.

Sternberg, Robert J., and Li-Fang Zhang, eds. Perspectives on Thinking, Learning, and Cognitive Styles. New York: Routledge, 2011. Print.

How can a company's customer service be improved?

Everybody seems to realize that there is a consumer perception that customer service is lacking in the business world today. What is more difficult, however, is how to reverse this perception and make customers feel good again. This is much easier to achieve in the small business community than it is in large companies. Ultimately, customers want to feel important. They are spending their hard earned money on your company and they want to feel...

Everybody seems to realize that there is a consumer perception that customer service is lacking in the business world today. What is more difficult, however, is how to reverse this perception and make customers feel good again. This is much easier to achieve in the small business community than it is in large companies. Ultimately, customers want to feel important. They are spending their hard earned money on your company and they want to feel welcomed.

One strategy for improving customer service is improving communication. Customers want to get to know you and what your company is about. This can be accomplished by being available and willing to communicate with customers. Businesses need to be available for their customers at all hours. Most customers are more comfortable talking to people than they are machines. Having questions answered on the Internet is not as important as customers being able to talk to knowledgeable professionals in person or on the phone. If it is a small company, speaking with the owner or management of the company is even more important. In a small company setting, availability of ownership is an important component. The customer feels that they are speaking to the person with the most knowledge and that has the greatest stake in keeping them happy. Improving communication and availability are the most important strategies that can be utilized to improve customer service for a company.

What is Klinefelter syndrome? |

Causes and Symptoms

Klinefelter syndrome
is caused by a variation in the number of sex chromosomes. Males normally possess one X and one Y chromosome, while females normally have two X chromosomes. When an embryo has two X chromosomes and one Y chromosome (XXY), normal development and reproductive function are hampered, and the boy shows the symptoms of Klinefelter syndrome. These symptoms include breast development, underdevelopment of sex organs, and school or social difficulties. The major symptom is sterility or very reduced fertility, although affected males have normal erections. The testes remain small after puberty and produce few, if any, sperm. Sex drive may also be low.

In adolescence, breast tissue often develops significantly. In addition, normal facial and body hair may not develop in these boys. Although they usually grow quite tall, young men with Klinefelter syndrome often have disproportionate limbs and are less physically strong or coordinated than their peers. Some affected individuals exhibit some degree of subnormal intelligence. Others lack self-confidence or experience difficulties in learning language and speech or in concentrating.

Treatment and Therapy

Klinefelter syndrome is diagnosed using a karyotype, an analysis of the chromosomes from blood or cheek cells. It can determine the presence of forty-seven chromosomes, including one Y and two X. Although Klinefelter syndrome is genetic and cannot be cured, testosterone can be administered orally, intravenously, or transdermally to supplement the usually insufficient amount produced by the boy’s own testes. This therapy should enhance male physical development by increasing the size of the penis, causing hair
growth and greater muscle bulk, and deepening the voice. Other benefits may include increased concentration, greater physical strength and energy, and higher sex drive.

Hormone therapy cannot increase the size of the testes, cure sterility, or reverse breast tissue development, which can only be treated by surgical removal. It may, however, increase self-esteem and a sense of masculinity, thereby easing social interactions.

For children with Klinefelter syndrome who experience difficulty with language development, early speech therapy interventions and educational assistance are recommended. Counseling and behavioral training may help with social interaction.

Perspective and Prospects

Found in about one out of every five hundred born, Klinefelter syndrome is the most common human chromosomal variation. Described by Harry Klinefelter in 1942, its cause was discovered by Patricia Jacobs and John Strong in 1959.

Men with Klinefelter syndrome are at higher risk of developing heart or lung disease, diabetes, hypothyroidism, dental complications, osteoporosis, breast or lung cancer, venous disease, depression, and autoimmune disorders. Nevertheless, the average life expectancy for those with Klinefelter syndrome is about the same as men without the condition.

Bibliography

A.D.A.M. Medical Encyclopedia. "Klinefelter Syndrome." MedlinePlus, November 2, 2012.

Bandmann, H.-J., and R. Breit, eds. Klinefelter’s Syndrome. New York: Springer, 1984.

Klinefelter Syndrome and Associates. "Frequently Asked Questions Related to 47, XXY." Genetic.org, 2012.

Kronenberg, Henry M., et al., eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia: Saunders/Elsevier, 2011.

Martin, Richard J., Avroy A. Fanaroff, and Michele C. Walsh, eds. Fanaroff and Martin’s Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant. 9th ed. St. Louis, Mo.: Mosby/Elsevier, 2010.

Milunsky, Aubrey, and Jeff Milunsky, eds. Genetic Disorders of the Fetus: Diagnosis, Prevention, and Treatment. 6th ed. Hoboken, N.J.: Wiley-Blackwell, 2010.

Morales, Ralph, Jr. Out of the Darkness: An Autobiography of Living with Klinefelter Syndrome. Louisville, Ky.: Chicago Spectrum Press, 2002.

National Institute of Child Health and Human Development. "Klinefelter Syndrome: Condition Information." U.S. Department of Health and Human Services, National Institutes of Health, November 30, 2012.

Parker, James N., and Philip M. Parker, eds. The Official Parent’s Sourcebook on Klinefelter Syndrome. San Diego, Calif.: Icon Health, 2002.

Rosenblum, Laurie, and Kari Kassir. "Klinefelter Syndrome."Health Library, September 27, 2012.

Sørensen, Kurt. Klinefelter’s Syndrome in Childhood, Adolescence, and Youth: A Genetic, Clinical, Developmental, Psychiatric, and Psychological Study. Park Ridge, N.J.: Parthenon, 1988.

What is a lumbar puncture?

Indications and Procedures

A lumbar puncture, often referred to as a spinal tap, is indicated for the diagnosis of meningitis
because it is the best method for detecting meningeal irritation. A laboratory examination of the cerebrospinal fluid
(CSF) harvested through a lumbar puncture can detect problems relating to the brain and spinal cord. Meningitis cannot be diagnosed through imaging methods such as computed tomography (CT) scanning.

Similarly, some subarachnoid (brain) hemorrhages

involve the loss of so little blood that they are not detectable radiologically. When this is the case, the CSF may contain small amounts of blood that continues to be present in successive testing. If diagnosis is delayed, then the blood from a subarachnoid hemorrhage may have dissipated, making the CSF yellowish. This signifies that the blood in it is being metabolized. When this is the case, an immediate angiogram is indicated.

CSF withdrawn through a lumbar puncture should be examined immediately by a pathologist or hematologist to determine if blood is present or, if it is xanthochromic or yellowish, to ascertain if the protein level is abnormally high or a subarachnoid hemorrhage exists and blood is spreading over the surface of the brain. Such leakage may indicate an aneurysm and generally requires prompt surgery.

Although lumbar puncture is essentially a diagnostic tool, it is sometimes indicated when CSF has built up to dangerous levels in the spinal canal and the patient is hydrocephalic. In such instances, excess CSF can be withdrawn from the spinal canal, but it is imperative that the cause of the buildup be immediately determined and treated.

Patients undergoing lumbar punctures lie on their side, with their chin down and their knees drawn up to separate the vertebrae. Local anesthetic is used to numb the area surrounding the lower vertebrae. A hollow needle is inserted between two lower vertebrae and pushed into the spinal canal. The entire procedure takes about twenty minutes and involves minimal discomfort. The puncture wound left by the needle is covered with a sterile bandage. Patients may experience a headache following the procedure, but it usually disappears quickly. If it does not disappear within a few days, a small amount of the patient’s blood can be injected into the site, creating a patch that should eliminate the headache.

Uses and Complications

Lumbar puncture is used to inject dyes into the spinal canal to serve as a contrast medium in diagnostic procedures involving x-rays, particularly myelography. It is also used to introduce medications into the CSF for the treatment of certain types of cancer. This use, often appropriate in cases of leukemia and carcinomas of the nervous system, is frequently employed in pediatric care.

Some surgical procedures require that patients be awake during surgery. In such cases, local anesthetics are introduced into the spinal canal through lumbar puncture, allowing patients to remain conscious while rendering them insensate.

As with any invasive procedure, there is risk of infection, but it is minimal. The procedure is performed under sterile conditions. One danger, in the case of a subarachnoid hemorrhage, is blood loss. Bleeding, in rare cases, may become uncontrollable and result in death. One cautionary note is that a lumbar puncture should never be performed in cases where a brain abscess is suspected unless reliable CT scans or other tests have failed to reveal a mass or reveal only a small mass.

Lumbar puncture in and of itself is not a high-risk procedure, although the conditions that require its use often involve high risks for the patient. It is advisable in most cases that the procedure be performed in a location where immediate surgery can be carried out if the patient’s condition deteriorates suddenly.

Perspective and Prospects

The earliest use of CSF in diagnosis was in the nineteenth century, when such primitive tools as sharpened bird quills were used to penetrate the lumbar region. The technique came into its own in the mid-twentieth century, when most problems of the central nervous system were diagnosed through an examination of the CSF.

Because of the importance of CSF in diagnosing meningitis, cerebral hemorrhages, and other dangerous conditions, the lumbar puncture procedure has seen considerable progress and become increasingly sophisticated. However, the imaging tools currently available to surgeons, neurologists, hematologists, and pathologists are so advanced and accurate that lumbar puncture is used as a diagnostic tool less often than in the past.

Bibliography

Bowden, Vicky R., and Cindy Smith Greenberg. Pediatric Nursing Procedures. 3d ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2012.

Colyar, Margaret R. Well-Child Assessment for Primary Care Providers. Philadelphia: F. A. Davis, 2003.

Doherty, Gerard M., ed. Current Diagnosis and Treatment: Surgery. 13th ed. New York: Lange Medical Books/McGraw-Hill, 2010.

Dougherty, Lisa, and Sara E. Lister, eds. The Royal Marsden Hospital Manual of Clinical Nursing Procedures. 8th ed. Ames, Iowa: Wiley-Blackwell, 2011.

Dugdale, David C., Kevin Sheth, and David Zieve. “Cerebral Spinal Fluid (CSF) Collection.” MedlinePlus, June 18, 2011.

Lukas, Rimas, and Michael Woods. “Lumbar Puncture.” Health Library, May 20, 2013.

McAllister, Leslie D., et al. Practical Neuro-oncology: A Guide to Patient Care. Boston: Butterworth-Heinemann, 2002.

How do the images of travel in part 46 of "Song of Myself" contribute to the poem’s theme?

In section 46 of "Song of Myself," Walt Whitman provides extensive travel imagery: "I tramp a perpetual journey" (1202), Whitman says. "My signs are a rain-proof coat, good shoes, and a staff cut from the woods" (1203). In general, the travel imagery in this section supports one of the poem's most important themes: the idea of the expansive, untamed individual/self.

In section 24, Whitman declares himself to be "a kosmos" (497). Furthermore, in the poem's...

In section 46 of "Song of Myself," Walt Whitman provides extensive travel imagery: "I tramp a perpetual journey" (1202), Whitman says. "My signs are a rain-proof coat, good shoes, and a staff cut from the woods" (1203). In general, the travel imagery in this section supports one of the poem's most important themes: the idea of the expansive, untamed individual/self.

In section 24, Whitman declares himself to be "a kosmos" (497). Furthermore, in the poem's final section, Whitman claims "I too am not a bit tamed, I too am translatable" (1332). Both of these ideas point to Whitman's conception of self, which argues that identity is as broad as the universe and as wild as the American frontier. In essence, Whitman proposes a conception of individuality that hinges upon multiplicity, freedom, and expansive diversity.

The travel imagery in section 46 supports this notion in a couple of ways. First, by presenting himself as a "perpetual" wanderer, Whitman adds further support to the idea that his individuality is untamed, raw, unpredictable, and authentic. Furthermore, the process of traveling, of wandering the "landscapes of continents and the public road" (1209) implicitly requires one to be exposed to a wide diversity of life and experience. This process is crucial for Whitman, as his conception of self relies upon vast expanses of diversity to function. As such, it's clear that the idea of travel, of rejecting stable "society" and setting out for interesting new places, is an integral part of Whitman's expansive, democratic, and wild conception of self, and so the travel imagery in section 46 becomes a vital contributor to one of the poem's most important themes.   

What are culture-bound syndromes? |

Introduction

In the late 1960s, the fields of psychology and psychiatry developed a particular interest in how cultural factors shape the manifestation of mental disorders. Before that time, some believed that mental disorders were largely universal in their underlying causes and expression. Several decades of cross-cultural research highlighted the limitations of this view by uncovering potentially important differences in the prevalence and expression of certain psychological conditions across the world.

Models

There are two major models of psychological disorders that are limited to certain cultures. The first, a pathogenic-pathoplastic model, presumes that mental disorders across the world are identical in their underlying causes (pathogenic effects) but are expressed differently depending on cultural factors (pathoplastic effects). According to this model, cultural influences do not create distinctly different disorders but merely shape the outward expression of existing disorders in culturally specific ways.

Harvard University’s Arthur Kleinman and some other cultural anthropologists contended that this model underestimates the cultural relativity of mental disorders. In its place, Kleinman proposed the new cross-cultural psychiatry model, which maintains that many culture-bound syndromes are causally distinct conditions that bear no underlying commonalities to those in Western culture. According to this alternative model, non-Western disorders are not merely culturally specific variations of Western disorders.

In some ways, these competing models parallel the etic-emic distinction in cross-cultural psychology. As noted by University of Minnesota psychiatrist Joseph Westermeyer and others, the term “etic” refers to universal, cross-cultural phenomena that can occur in any cultural group. Conversely, the term “emic” refers to socially unique, intracultural perspectives that occur only within certain cultural groups. There is probably some validity to both perspectives. Some culture-bound syndromes may be similar to conditions in Western culture, whereas others may be largely or entirely distinct from these conditions.

Examples

Some culture-bound conditions appear to fit a pathogenic-pathoplastic model. For example, seal hunters in Greenland sometimes experience kayak angst, a condition marked by feelings of panic while alone at sea, along with an intense desire to return to land. Kayak angst appears to bear many similarities to the Western condition of panic disorder with agoraphobia and may be a culturally specific variant of this condition.

A culture-bound syndrome widespread among the Japanese is taijin-kyofusho, an anxiety disorder characterized by a fear of offending others, typically by one’s appearance or body odor. Some authors have suggested that taijin-kyofusho is a culturally specific variant of the Western disorder of social phobia, a condition marked by a fear of placing oneself in situations that are potentially embarrassing or humiliating, such as speaking or performing in public. Interestingly, Japan tends to be more collectivist than most Western countries, meaning its citizens view themselves more as group members than individuals. In contrast, most Western countries tend to be more individualistic than Japan, meaning their citizens view themselves more as individuals than as group members. As a consequence, taijin-kyofusho may reflect the manifestation of social phobia in a culture that is highly sensitive to the feelings of others.

In contrast, other culture-bound conditions may be largely distinct from Western disorders and therefore difficult to accommodate within a pathogenic-pathoplastic model. In koro (genital retraction syndrome), a condition found primarily in southeast Asia and Africa, individuals believe their sexual organs (for example, the penis in men and breasts in women) are retracting, shrinking, or disappearing. Koro is associated with extreme anxiety and occasionally spreads in contagious epidemics marked by mass societal panic. Although koro bears some superficial similarities to the Western diagnosis of hypochondriasis, it is sufficiently different from any Western condition that it may be a distinctive disorder in its own right.

Another potential example is the Malaysian condition of amok. In amok, individuals, almost always men, react to a perceived insult by engaging in social withdrawal and intense brooding, followed by frenzied and uncontrolled violent behavior. Afflicted individuals, known as "pengamoks," often fall into a stupor after the episode and report memory loss for their aggressive actions. Although amok may be comparable in some ways to the sudden mass shootings occasionally observed in Western countries, such shootings are rarely triggered by only one perceived insult or associated with stupor following the episode. Amok, incidentally, is the origin of the colloquial phrase “running amok.”

Psychiatric Classification

The fourth edition of the American Psychiatric Association’s
Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV) provided a list of twenty-five culture-bound syndromes, including taijin-kyofusho, koro, and amok. Appearing in an appendix of the fourth edition, this list was the first official attempt by the mental health community to recognize culture-bound syndromes as worthy of research and clinical attention. The 2000 text revision of the DSM-IV (the DSM-IV-TR) added an outline of issues and factors that clinicians should consider when making diagnoses for culturally diverse patients.

Nevertheless, some researchers criticized the DSM-IV’s list of culture-bound syndromes. Some, like McGill University psychiatrists Lawrence J. Kirmayer and Eric Jarvis, argued that some of these “syndromes” are not genuine mental disorders but rather culturally specific explanations for psychological problems familiar to Western society. They cited the example of dhat, a culture-bound condition in the DSM-IV appendix that is prevalent in India, Pakistan, and neighboring countries. Dhat is commonly associated with anxiety, fatigue, and hypochondriacal worries about loss of semen. As Kirmayer and Jarvis observe, many or most individuals with dhat appear to suffer from depression, so dhat may merely be a culturally specific interpretation of depressive feelings.

Other critics charged that DSM-IV’s list of culture-bound syndromes was marked by Western bias and that some well-established psychological conditions in Western culture are in fact culture bound. For example, based on a comprehensive review of the literature, Harvard University psychologist PamelaKeel and Michigan State University psychologist Kelly Klump argued persuasively that bulimia nervosa (often known simply as bulimia), an eating disorder often characterized by repeated cycles of binging and purging, is a culture-bound syndrome limited largely to Western culture. Indeed, the few non-Western countries in which bulimia has emerged, such as Japan, have been exposed widely to Western ideals of thinness in recent decades. In contrast, as Keel and Klump noted, anorexia nervosa (often known simply as anorexia) appears to be about equally prevalent in Western and non-Western countries.

For the fifth edition of the DSM (DSM-5), published in 2013, American Psychiatric Association sought to address some of these concerns. While the DSM-5 retains the list of culture-bound syndromes, along with their "idioms of distress" and explanations, in an appendix, it also integrate their symptoms throughout the manual as additions to existing classifications. For example, "offending others," a symptom of taijin-kyofusho, was listed under the diagnostic criteria for social anxiety disorder. Another modification was the addition of an interview guide with questions about the patient's cultural, racial, ethnic, and religious heritage, which is intended to afford patients an opportunity to describe their condition in their own terms and help clinicians better interpret this information.

Mental health professionals are increasingly recognizing that psychological conditions are sometimes influenced by sociocultural context and that such context must be taken into account in their diagnoses. More research is needed to ascertain how best to classify culture-bound syndromes and integrate cultural influences into diagnostic practices.

Bibliography

Aneshensel, Carol S., Alex Bierman, and Jo C. Phelan. Handbook of the Sociology of Mental Health. Dordrecht: Springer, 2013. Print.

Kirmayer, Lawrence J., and Eric Jarvis. “Cultural Psychiatry: From Museums of Exotica to the Global Agora.” Current Opinion in Psychiatry 11.2 (1998): 183–89. Print.

Mezzich, Juan E., et al. “The Place of Culture in DSM-IV.” Journal of Nervous and Mental Disease 187.8 (1999): 457–64. Print.

Murphy, Jane M. “Psychiatric Labeling in Cross-cultural Perspective.” Science 191.2431 (1976): 1019–28. Print.

Paniagua, Freddy A.. "Assessment and Diagnosis in a Cultural Context." Culture and Therapeutic Process. Ed. Mark M. Leach and Jamie D. Aten. New York: Routledge, 2010. Print.

Paniagua, Freddy A., and Ann-Marie Yamada, eds. Handbook of Multicultural Mental Health: Assessment and Treatment of Diverse Populations. 2nd ed. Oxford: Elsevier, 2013. Print.

Simons, Ronald C., and Charles C. Hughes, eds. The Culture-Bound Syndromes: Folk Illnesses of Psychiatric and Anthropological Interest. Boston: Reidel, 1986. Print.

Sue, Derald Wing, and David Sue. Counseling the Culturally Diverse: Theory and Practice. Hoboken: Wiley, 2012. Print.

Tseng, Wen-Shing. “From Peculiar Psychiatric Disorders Through Culture-Bound Syndromes to Culture-Related Specific Syndromes.” Transcultural Psychiatry 43.4 (2006): 554–76. Print.

Westermeyer, Joseph. “Psychiatric Diagnosis across Cultural Boundaries.” American Journal of Psychiatry 142.7 (1985): 798–805. Print.

What is oxygen therapy? |

Indications and Procedures

The major indication for oxygen therapy is cyanosis, in which the skin assumes a bluish tint as a result of hypoxia, a reduced arterial saturation of oxygen to the tissues. In cases of extreme breathlessness, which may be caused by extreme physical exertion, hypoxia may occur, but the condition in most cases reverses itself within minutes if the affected person rests.

In older people whose circulatory systems have been compromised by such conditions as arteriosclerosis (narrowing of the arteries), hypoxia may be chronic. Asthmatics often require immediate oxygen therapy during severe attacks. People suffering from influenza or pneumonia may have accumulated secretions in their airways that limit the amount of oxygen that can reach their tissues. Such people are usually given oxygen administered through either a nasal catheter or a face mask.

In instances where respiratory difficulties persist, as in emphysema
or chronic bronchitis, patients often receive prescriptions for oxygen cylinders for home use. They may also benefit from the home installation of an oxygen concentrator, a machine that removes oxygen from the atmosphere and remixes it in high concentrations with air. Such machines can supply oxygen-enhanced air to various rooms within a house so that ambulatory patients can breathe it for prolonged periods without being confined to one location. Some patients must breathe oxygen-enhanced air for up to fifteen hours a day.

Uses and Complications

Oxygen therapy is routinely used by anesthesiologists during many surgical procedures, but very high oxygen concentrations are usually avoided. Warm, humidified oxygen is preferred in surgical situations to prevent condensation and inordinate cooling, which can lead to complications. Such therapy is often administered through a catheter and used postoperatively for up to five days to prevent hypoxemia (reduced oxygen in the blood). In emergency rooms, pure oxygen is frequently given to patients in acute distress.

In some situations, physicians must use medications such as naftidrofuryl to reduce the brain’s requirement for oxygen where hypoxemia is present, and brain damage may result if this complication is not addressed immediately. A thrombus (blood clot) may reduce blood flow substantially and reduce to dangerous levels the supply of oxygen to the brain and tissues. In such situations, anticoagulants such as heparin or warfarin often reduce or eliminate the thrombus and restore the body’s circulation of oxygen.

Bibliography

Perry, Anne Griffin, and Patricia A. Potter, eds. Clinical Nursing Skills and Techniques. 6th ed. St. Louis, Mo.: Mosby/Elsevier, 2006.

Rosdahl, Caroline Bunker, and Mary Kowalski, eds. Textbook of Basic Nursing. 9th ed. Philadelphia: Lippincott Williams & Wilkins, 2008.

Sheldon, Lisa Kennedy. Oxygenation. 2d ed. Sudbury, Mass.: Jones and Bartlett, 2008.

Tallis, Raymond C., and Howard M. Fillit, eds. Brocklehurst’s Textbook of Geriatric Medicine and Gerontology. 7th ed. Philadelphia: Saunders/Elsevier, 2010.

What is gluten intolerance? |

Causes and Symptoms

Gluten, a protein found in wheat, rye, and barley grains, is a common part of the twenty-first century diet. However, in people who develop gluten intolerance—which most commonly develops between the ages of twenty and forty—gluten triggers a specific immune system response. Gluten intolerance, or gluten sensitivity, comprises celiac disease, which is a gastric reaction, and dermatitis herpetiformis (DH), which is primarily a skin-based reaction. Unlike the majority of food allergies that are mediated by immunoglobulin (Ig) E antibodies, gluten ingestion in patients with DH signals the body to develop an immune response that is mediated by IgA instead. IgA antibodies build up and attack tissue transglutaminase (tTG) and epidermal transglutaminase, enzymes that break down gliadin, a component of wheat gluten. Gliadin, and related substances in rye and barley grains, appears to be the antigen, or trigger, of the immune response that leads to the characteristic symptom of DH—an intensely itchy and progressive skin rash. Indeed, instead of relying on only a dietary challenge for diagnosis of DH, this gluten sensitivity may be diagnosed by immunofluorescence to identify IgA deposits in skin lesions or by screening for the disease-specific presence of a tTG attack.

Symptoms of gluten intolerance in DH begin slowly as small, itchy areas on the skin but progress rapidly to extremely blistered, burning, and itchy lesions that appear in groups, often symmetrically. Affected areas are most often found on the knees, elbows, buttocks, and back. In severe skin disease, prodromal irritation may occur at sites of new lesions. Gastrointestinal discomfort, ranging from stomach pain to oral ulcers, has been reported infrequently along with the primarily dermal symptoms of DH.

Even without gastric symptoms, gastrointestinal biopsies of people with DH reveal abnormal changes to parts of the gastrointestinal wall and IgA deposits in parts of the gastrointestinal wall. Increased tTG reactivity appears proportional to the likelihood of this gastric involvement. Because of this gastric link, some researchers consider DH to be a precursor to the development of celiac disease and related malabsorption problems if the skin condition remains untreated.

Treatment and Therapy

Treatment of DH is twofold. First, symptomatic relief is provided by oral sulfones—dapsone and sulfasalazine—to reduce lesions. Sulfones work by unknown mechanisms, possibly related to enzyme stabilization, and they quickly reduce the severity and number of skin lesions, often within only two days. Dapsone, 150 to 200 milligrams daily, is the first-line agent, and the dose can be reduced to 50 to 100 milligrams daily after severe lesions have healed. Because dapsone in particular is associated with high rates of peripheral neuropathy, at times with sensory loss, sulfasalazine is a secondary sulfone choice. Potential side effects of any sulfone treatment include blood-related problems, such as anemia and decreased leukocyte counts. When an alternative to symptomatic sulfone treatment is required because of such side effects, tetracycline or minocycline may be used successfully but with less dramatic rates of improvement.

Gluten removal from the diet is the only treatment known to induce disease remission, to reduce the IgA accumulation to nearly zero, to heal existing lesions, and to prevent eruption of new lesions. In severe disease occurrences, full improvement of symptoms may take as long as two years; most often, six months of a gluten-free diet will allow a patient to discontinue sulfone treatment without a disease flare. A diet without wheat, rye, or barley must be continued indefinitely for successful disease control, because dermal symptoms return as soon as gluten is reintroduced. Rice, corn, and pure oats are recommended replacement grains. Consultation with a dietician is often suggested to ensure that the gluten-free diet provides adequate nutritional needs and to learn about ways to avoid hidden sources of gluten.

Perspective and Prospects

As early as the 1930s, dentist Weston Price associated greater amounts of processed foods in American diets with increasingly poor oral, digestive, and overall health. During the 1940s and 1950s, Willem Dicke of the Netherlands noted that children with nonspecific health complaints, including gastric pain, experienced improvement during food rations, when most grains were unavailable. Dicke expanded this observation with extensive research, presentations, and publications that pointed to early identification of DH and celiac disease.

In the second half of the twentieth century, more research evolved to identify biopsy results and immune responses in patients with skin lesions as similar to those in patients with gastric symptoms of celiac disease; the term “nonceliac gluten sensitivity” (NCGS) was coined to identify patients whose skin and mild gastric symptoms improved despite negative test results for celiac disease, and the differentiation of DH and celiac disease began. However, since the diagnosis of NCGS is based mainly on having symptoms similar to celiac disease but testing negative for it, the diagnosis remains somewhat controversial in the medical community. Some clinicians contest the role that gluten plays in the disorder. One 2013 Australian study found no significant difference between reactions to a gluten-free diet and a placebo in patients with presumptive NCGS, but other studies have found improvement in symptoms with the gluten-free diet.

As research about the abnormal immune system response to gluten continues, potential links to other autoimmune disorders, such as autoimmune thyroid disease, multiple sclerosis, and irritable bowel syndrome, have been identified. Additionally, researchers are trying to determine how closely linked celiac disease and DH may be and whether lack of disease control in either gluten sensitivity may lead to progressive gastric disease, malabsorption, and even lymphoma.

Awareness of gluten sensitivity increased greatly in the twentieth century and into the twenty-first, which has made identification of gluten-free foods simpler. Still, gluten is a common filler ingredient and may be hidden in foods such as gravy, beer, or soy sauce; medications such as vitamin supplements; and even makeup such as lip balm. As with many chronic conditions, patient education is key to reducing symptoms and improving quality of life.

Researchers at the Mayo Clinic indicated that cases of celiac disease rose considerable in the first decade of the twenty-first century, plateauing in 2004; experts believe that this is largely due to greater awareness of the disease and better diagnostic tools rather than an actual increase in prevalence. However, the prevalence of NCGS is harder to pin down, as it is a newer diagnosis that is not as well understood. A 2015 review found that studies have estimated the rate at anything from 0.5 percent to 13 percent of the population. A 2013 Swedish report stated that infants, beginning at four months, can bolster their defenses against celiac disease by consuming small doses of grain-based foods in tandem with breastfeeding.

Bibliography

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Czaja-Bulsa, Grazyna. "Non Coeliac Gluten Sensitivity—A New Disease with Gluten Intolerance." Clinical Nutrition 34.2 (2015): 189–94. Print.

Feldman, M., L. S. Friedman, and L. J. Brandt. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 9th ed. Maryland Heights: Saunders, 2010. Print.

Gluten Intolerance Group of North America. GIG Newsletter Education Bulletin: Dermatitis Herpetiformis. Auburn: Author, 2009. Print.

Habif, T. P. “Vesicular and Bullous Diseases.” Clinical Dermatology. 5th ed. Rockville: Mosby, 2009. Print.

Humbert, P., F. Pelletier, and B. Dreno, et al. “Gluten Intolerance and Skin Diseases.” European Journal of Dermatology 16.1 (2006): 4–11. Print.

Ivarsson A. "Prevalence of Childhood Celiac Disease and Changes in Infant Feeding." Pediatrics 131.3 (2013): 687–94. Print.

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"Middle-Class Children More Likely to Be Diagnosed with Gluten Intolerance." Telegraph [London] 23 Jan. 2015: 4. Print.

Molina-Infante, J., S. Santolaria, D. S. Sanders, and F. Fernández-Bañares. "Systematic Review: Noncoeliac Gluten Sensitivity." Alimentary Pharmacology & Therapeutics, 41.9 (2015): 807–20. Print.

Sampson, H. A., and A. W. Burks. “Adverse Reactions to Food: Non-IgE-Mediated Food Hypersensitivity.” Middleton’s Allergy: Principles and Practice. Ed. N. F. Adkinson et al. 7th ed. Rockville: Mosby, 2008. Print.

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Wangen, Stephen. Healthier Without Wheat: A New Understanding of Wheat Allergies, Celiac Disease, and Non-Celiac Gluten Intolerance. Seattle: Innate Health, 2009. Print.

In The Giver, what purpose does a comfort object serve for society?

While the comfort object appears to serve a more significant purpose for an individual than it does for society as a whole, let's look at how it serves  purposes for each.

First and foremost, it is used to comfort individual infants. In our society we would call the comfort object something like, "his favorite teddy bear." In their community, it is less personalized by name and is also taken away from the child at a...

While the comfort object appears to serve a more significant purpose for an individual than it does for society as a whole, let's look at how it serves  purposes for each.

First and foremost, it is used to comfort individual infants. In our society we would call the comfort object something like, "his favorite teddy bear." In their community, it is less personalized by name and is also taken away from the child at a predetermined age, perhaps because they view it is a crutch preventing further growth at an older age. So, the purpose it serves for an individual is simply to soothe an infant.

For society, the argument could be made that it serves the purpose of providing a measurable level of affection and comfort. In this community it appears that being able to quantify things is important, so this comfort object could be seen as just one more item on a checklist of "good nurturing." If a child did not bond with the comfort object, I could also see where this particular community might use that as a reason to consider the child abnormal or lacking in development. In that case, the comfort object might also be an evaluative tool for nurturers and parents.