What is the hypothalamus? |

Structure and Functions

The hypothalamus is a small, cone-shaped structure located near the center of the brain immediately below the thalamus. The hypothalamus has many nuclei and fiber tracts. It forms part of the walls and floor of the central chamber of the cerebral ventricles, which is known as the third ventricle. Neurons in the hypothalamus extend axons to the pituitary gland that is hanging on a stalk underneath the hypothalamus.

The hypothalamus controls many automatic functions of the body. Its overall function is to maintain normal, healthy conditions in the body by governing the autonomic nervous system and controlling pituitary output. Its specific functions are controlling the release of eight major hormones in the body, regulating body temperature, controlling food and water intake, controlling daily cycles in physiological state and behavior, mediating emotional responses, and regulating sexual behavior and reproduction.

Disorders and Diseases

If the hypothalamus is not functioning properly, the autonomic nervous system can send wrong neurosignals to the body that can make the victim feel stressed and emotionally empty. This can lead to disordered sleep, dysfunction of the immune system, altered body temperature, or multiple hormonal dysfunctions. These conditions often lead to depression, hyperactivity, malfunctioning of normal brain and limbic activities, or abnormal responses to stress. Disturbances in neural pathways that connect the hypothalamus and thalamus and control mood appear to be related to some of the symptoms of schizophrenia.

Obesity and related disorders are directly related to the critical role that the hypothalamus plays in the central regulation of appetite and metabolism. Insufficient production of antidiuretic hormone by the hypothalamus may cause diabetes insipidus. When the thirst center in the anterior hypothalamus is stimulated, polydipsia occurs, which can lead to polyuria.

Treatment of hypothalamic disorders depends on the cause of the dysfunction. If it is due to a tumor, the growth is either surgically removed or treated with radiation. If it is due to hormonal deficiencies, the missing hormones are replaced. Other specific treatments may be applied if the malfunction is due to infection, bleeding, or other causes.

Perspective and Prospects

The homeostatic function of the hypothalamus was suggested by Claude Bernard in the late 1800s. Many initial studies were focused on identifying the boundaries, structural components, nuclei, tracts, and interconnections of the hypothalamus. During the latter half of the twentieth century, interest shifted to the functions of the hypothalamus that were involved in emotional expression, disease, controlling metabolism, and producing neuroendocrine secretions. This emphasis has led to a better understanding and treatment of medical problems and chemical imbalances associated with hypothalamic dysfunctions.

Bibliography

Hadley, Mac E., and Jon E. Levine. Endocrinology 6th ed. Upper Saddle River, N.J.: Pearson, 2007.

Jasmin, Luc. "Hypothalamus." MedlinePlus, November 2, 2012.

Norwood, Diane Voyatzis. "Diabetes Insipidus." Health Library, March 15, 2013.

Rennert, Nancy J. "Hypothalamus." MedlinePlus, December 11, 2011.

Stoll, Walt, and Jan DeCourtney. Recapture Your Health. Boulder, Colo.: Sunrise Health Coach, 2006.

Swaab, Dick F. Human Hypothalamus: Basic and Clinical Aspects, Part 2: Handbook of Clinical Neurology. Amsterdam: Elsevier, 2003.

What is male circumcision? |

Indications and Procedures

Routine circumcision of the newborn male—in which the foreskin of the penis is stretched, clamped, and cut—is becoming an increasingly controversial procedure. Famed pediatrician Benjamin Spock once contended that circumcision is a good idea, especially if most of the boys in the neighborhood are circumcised; then a boy feels “regular.” Yet, many wonder if that is justification for circumcision. Allowing routine circumcision of newborns as a religious and cultural rite still leaves the debate over medical necessity. The United States is the only country in the world that circumcises a majority of newborn males without a religious reason. In fact, circumcision has been termed a “cultural surgery.”

True medical indications for the surgery are seldom present at birth. Such conditions as infections of the head and/or shaft of the penis may be indications for circumcision; an inability to retract the foreskin in the newborn (phimosis) is not an indication. Some argue that circumcision should be delayed until the foreskin has become retractable, making an imprecise surgical procedure presumably less traumatic. In 96 percent of infant boys, however, the foreskin is not fully retractable; it is normally so tight and adherent that it cannot be pulled back and the penis cleaned. By age three, that percentage decreases to 10 percent.

There are other definite contraindications to newborn circumcision. Circumcising infants with abnormalities of the penal head or shaft makes treatment more difficult because the foreskin may later be needed for use in reconstruction. Prematurity, instability, or a bleeding problem also preclude early circumcision. The foreskin is a natural protective membrane, representing 50 to 80 percent of the skin system of the penis, having 240 feet of nerve fibers, more than one thousand nerve endings, and three feet of veins, arteries, and capillaries. It keeps the sensitive head protected, facilitating intercourse, and prevents the surface of the glans from thickening and becoming desensitized. Also, within the inner surface of the foreskin are a series of tiny ridged bands that contribute significantly to stimulating the glans.

The two most persistent arguments for the operation, however, are the risks of infection and cancer in the uncircumcised. Without circumcision, smegma accumulates beneath the base of the covered head of the penis. This cheeselike material of dead skin cells and secretions of the sweat glands is thought to be a cause of cancer of the penis and prostate gland in uncircumcised men and cancer of the cervix in their female partners. Doctors who argue against circumcision, however, say that the presence of smegma in the uncircumcised is simply a sign of poor hygiene and that poor sexual hygiene, inadequate hygienic facilities, and sexually transmitted diseases cause an increased incidence of cancer in ethnic groups or populations that do not practice circumcision. Doctors who argue against circumcision also point out that complete circumcision is found as often in male partners of women without cancer of the cervix as in male partners of women who have cervical cancer. In Sweden, moreover—where
newborn circumcision is not routinely practiced but where good hygiene is practiced—the rates of these cancers are essentially the same as those found in Israel, where ritualistic circumcision is practiced.

The increased incidence of urinary tract infections and sexually transmitted diseases (STDs) in uncircumcised males sufficiently argues for circumcision, say its proponents. They warn that the intact foreskin invites bacterial colonization, which leads to urethral infection ascending to the bladder that ultimately may spread upward to the kidneys and sometimes cause permanent kidney damage. On the other hand, no proof exists that uncircumcised male infants who sustain urinary tract infections will have future urologic problems. Furthermore, the operation is not a simple procedure and is not without peril. Penile amputation, life-threatening infections, and even death have been well documented.

Slightly increased rates of infection with sexually transmitted diseases in the uncircumcised argue the case for some proponents, but it is Acquired immunodeficiency syndrome (AIDS)
that they most fear. In Africa, where male circumcision is seldom practiced, the acquisition of AIDS by heterosexual men from infected women during vaginal intercourse is the most common mode of transmission.

Proponents say that infection with Human immunodeficiency virus (HIV)
, the virus that leads to AIDS, depends on a break or an abrasion of the skin to gain entry. The intact foreskin provides a site for the transfer of infected cervical secretions. In Africa, doctors at the University of Nairobi noted a relationship of HIV infection to genital ulcers and lack of circumcision. Uncircumcised men had a history of genital ulcers more often than did the circumcised, and they were more often HIV-positive. They were also more frequently HIV-positive even if they did not have a history of genital ulcer disease.

Every evaluation of circumcision, pro or con, should reflect the confounding genetic and environmental variables, as well as the actual increased risks and benefits. All the pros and cons should be explained to parents before informed consent is obtained.

Uses and Complications

In 1989, the American Academy of Pediatrics’ Task Force on Circumcision concluded that “newborn circumcision has potential medical benefits and advantages as well as disadvantages and risks. When circumcision is being considered, the benefits and risks should be explained to the parents and informed consent obtained.” This neutral statement does not lessen the anxiety of parents who are trying to weigh the pros and cons of routine newborn circumcision, but examination of the evidence does allow parents to weigh the individual benefits and risks and see if the scale tips in either direction.

Worldwide studies of predominantly uncircumcised populations have shown a higher incidence of urinary tract infection in boys during the first few months of life, which is the reverse of what is found in older infants and children, where girls predominate. In 1986, Brooke Army Medical Center in Fort Sam Houston, Texas, took a closer look. The doctors found the incidence of urinary tract infection in circumcised infant males to be 0.11 percent but 1.12 percent in the uncircumcised. Even without proof that the uncircumcised male infants who get urinary tract infections will have future urologic problems, the proponents for the surgical procedure claim about a 1 percent advantage.

The evidence for an increase in sexually transmitted diseases (such as genital herpes, gonorrhea, and syphilis) among the uncircumcised is conflicting. Furthermore, apparent correlations between circumcision status and these diseases do not reflect confounding genetic and environmental variables. It is also difficult to factor in the risk from HIV infections. The studies from Africa do not look at any variables in the transmission of HIV except circumcision status and previous history of genital ulcers. The nutritional and economic status of the men was not examined, even though it is known that malnourishment suppresses the immune systems. Moreover, if everyone practiced safer sex, the argument for circumcision would be moot.

Almost all the surgical complications of circumcision can be avoided if doctors performing the procedure adhere to strict asepsis, are properly trained and experienced in the procedure, remove the appropriate and correct amount of tissue, and provide adequate hemostasis. The variety of circumstances, populations, and physicians affects the incidence of complications. In the larger, teaching hospitals, often the newest physicians with the least experience or supervision perform the operation. As a result, complications may arise. Excessive bleeding is the most frequent complication. The incidence of bleeding after circumcision ranges from 0.1 percent to as high as 35 percent in some reports. Most of the episodes are minor and can be controlled by simple measures, such as compression and suturing, but some of these efforts can lead to diminished blood supply to the head and shaft of the penis with necrosis of the affected part. Chordee can result if improper technique or bad luck intervenes, and such penile deformity begets the risk of emotional distress. The urethral opening on the end of the penis can become infected or ulcerated when the glans is no longer protected by foreskin; such infection rarely occurs in the uncircumcised. Finally, any surgical
procedure runs the risk of infection. These localized infections rarely spread to the blood, but death from sepsis and its sequelae has been documented.

Overall, the surgical complication rate after circumcision runs around 0.19 percent, which could be lowered with strict protocols, meticulous technique, strict asepsis, and well-trained, experienced physicians. Strict protocols, it is hoped, would ensure that absolute contraindications to the procedure—such as anomalies of the penis, prematurity, instability, or a bleeding disorder—were honored.

Another human factor must be considered. Many insurance companies do not provide payment for newborn care, since it is considered preventive medicine. In 1997, a physician’s fee for performing a circumcision ranged to approximately $400, with a nationwide average of $137. Interestingly, a growing number of circumcised men are undergoing expensive foreskin restoration procedures.

In part because of an additional cost that arises with anesthesia, the vast majority of infant circumcisions are performed without pain control. The surgery is painful, yet some physicians claim that the minute that the operation ends, the circumcised baby no longer cries and frequently falls asleep. Continuing pain, therefore, is probably not present.

Another perspective to examine is the experience of adult males, who are circumcised by their own choice. Many complain of at least a week’s discomfort after the operation. The most compelling argument against adult circumcision, however, comes from their answer to “Would you do it again?” In one study of several hundred men who were circumcised as adults, they were asked five years later if they would do it again. All said no.

Perspective and Prospects

Routine newborn circumcision originated in the United States in the 1860s, ostensibly as prophylaxis against disease. Some medical historians, however, believe that nonreligious circumcision was a deliberate surgical procedure to desensitize and debilitate the penis to prevent masturbation. During this era, and for nearly one hundred years afterward, most American physicians viewed masturbation as an inevitable cause of blindness, weak character, insanity, nervousness, tuberculosis, sexually transmitted disease, and even death. One physician maintained that a painful circumcision would have a salutary effect upon the newborn’s mind, so that pain would be associated with masturbation. As late as 1928, the American Medical Journal published an editorial that justified male circumcision as an effective means of preventing the dire effects of masturbation. During World Wars I and II, soldiers were forcibly circumcised under threat of court martial, being told that the surgery was for reasons of hygiene and the prevention of epilepsy and other diseases.

Eventually, a general change in attitude occurred, notably in Great Britain and New Zealand, which virtually have abandoned routine circumcision. Rates of circumcision have also fallen dramatically in Canada, Australia, and even the United States. As recently as the mid-1970s, approximately 90 percent of US male babies were circumcised. Not until 1971 did the American Academy of Pediatrics determine that circumcision is not medically essential. In 1999, an estimated 65 percent of US male babies were circumcised; by 2010, the incidence of newborn circumcision had declined to 55 percent.

In 1971, the American Academy of Pediatrics’ Committee on the Fetus and Newborn issued an advisory that said, “There are no valid medical indications for routine circumcision in the neonatal period.” In 1978, when the American College of Obstetricians and Gynecologists affirmed this statement, the circumcision rate had already declined to an estimated 70 percent of newborn males, compared to previous rates of between 80 and 90 percent.

Undoubtedly, the future will bring improved surgical techniques. More emphasis will be placed on avoiding surgical complications by more rigid monitoring of the operation and who performs the procedure. It is unlikely that circumcision will disappear completely.

Organizations such as Doctors Opposing Circumcision and the National Organization to Halt the Abuse and Routine Mutilation of Males, however, are actively proposing an end to routine neonatal circumcision. Some nursing groups and concerned mothers have formed local groups to oppose circumcision in male neonates. They argue that subjecting a baby to this procedure may impair mother-infant bonding. Another question posed by some physicians and parents is the ethics involved in the unnecessary removal of a functioning body organ, particularly without the patient’s consent. Others claim that the baby’s rights are being violated, noting that it is the child who must live with the outcome of the decision to perform a circumcision. As a result of these efforts, the rates of circumcision will probably continue to fall.

Bibliography

Apuzzio, Joseph J., Anthony M. Vintzileos, and Leslie Iffy, eds. Operative Obstetrics. 3d ed. New York: Taylor & Francis, 2006.

Behrman, Richard E., Robert M. Kliegman, and Hal B. Jenson, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: Saunders/Elsevier, 2011.

Bigelow, Jim. The Joy of Uncircumcising! Exploring Circumcision—History, Myths, Psychology, Restoration, Sexual Pleasure, and Human Rights. Rev. ed. Aptos, Calif.: Hourglass, 1998.

"Circumcision." HealthyChildren.org. American Academy of Pediatrics, May 11, 2013.

"Circumcision." MedlinePlus, May 13, 2013.

Gollaher, David L. Circumcision: A History of the World’s Most Controversial Surgery. New York: Basic Books, 2000.

Kerr, Sarah J., and Michael Woods. "Child Circumcision." Health Library, May 13, 2013.

King, Lowell R., ed. Urologic Surgery in Neonates and Young Infants. Philadelphia: W. B. Saunders, 1998.

"Male Circumcision." Centers for Disease Control and Prevention, Apr. 15, 2013.

Snyder, Howard M. “To Circumcise or Not.” Hospital Practice 26 (January 15, 1991): 201–207.

Woods, Michael. "Newborn Circumcision." Health Library, Sept. 27, 2012.

What are cells? |

Structure and Functions

Cells are the basic components of all living things, and the human body is made up of approximately 10 trillion cells. Cells contain complex biochemical systems that use energy sources to power cellular activities such as growth, movement, and reaction to environmental changes or external stimuli. The information required to assemble the enzymatic and structural molecules involved in these activities is stored in a cell's deoxyribonucleic acid (DNA) and is duplicated and passed on in cell division.

A cell can be divided into two major internal regions, the nucleus and cytoplasm, which reflect a fundamental division of labor. In the nucleus are the DNA molecules that store the hereditary information required for cell growth and reproduction. The nucleus also contains enzymes that are capable of copying the hereditary information into ribonucleic acid (RNA), which is used as instructions for making proteins in the cytoplasm. Enzymes within the nucleus also duplicate the DNA in preparation for cell division. The cytoplasm makes proteins according to the directions copied in the nucleus and also synthesizes most other molecules required for cellular activities. The cytoplasm carries out several additional vital functions, including motility and the conversion of fuel substances into usable forms of chemical energy.

Cells are encapsulated by membranes. These layers of lipid and protein molecules, not much more than 7 to 8 nanometers thick, form an outer boundary, called the plasma membrane, that separates the cell contents from the exterior. Several internal membrane systems divide the cell interior into specialized compartments called organelles. The lipid part of membranes consists of a double layer of molecules called a bilayer. The lipid bilayer provides the structural framework of membranes and acts as a barrier to the passage of water-soluble substances. Membrane proteins, which are suspended in the lipid bilayer or attached to its surface, carry out the specialized functions of membranes.

The plasma membrane forming the outer cell boundary has a variety of functions. The most significant is the transport of substances between the cytoplasm and the cell’s exterior, which is carried out by proteins that form channels in the membrane. These channels pass specific water-soluble molecules or ions. The plasma membrane also contains proteins functioning as receptors, which recognize and bind to specific molecules from the surrounding medium. On binding to their target molecules, which include peptide hormones, many receptors trigger internal cellular responses that coordinate the activities of cells in tissues and organs. Other plasma membrane proteins recognize and adhere to molecules on the surfaces of other cells or to extracellular structures such as collagen. These adhesive functions are critical to the development and maintenance of tissues and organs. Other plasma membrane proteins identify cells as part of the individual or as foreign intruders.

The nucleus is separated from the cytoplasm by two concentric membranes, one layered just inside the other, forming a system known as the nuclear envelope. At closely spaced intervals, the envelope is perforated by pores, about 70 to 90 nanometers in diameter, which form channels between the nuclear interior and the surrounding cytoplasm. The pores are filled by a ringlike mass of proteins that control the movement of large molecules, such as proteins and RNA, through the nuclear envelope.

Within the nucleus are chromatin fibers containing the nuclear DNA, held in association with two major types of proteins, the histone and nonhistone chromosomal proteins. The histones are primarily structural molecules that pack DNA into chromatin fibers. The nonhistones include proteins that regulate gene activity. The hereditary information of the human nucleus is subdivided among forty-six linear DNA molecules. Each individual DNA molecule, with its associated histone and nonhistone proteins, is a chromosome of the nucleus.

Each segment of a chromosome containing the information used to make an RNA copy constitutes a gene. One type of gene encodes messenger RNA (mRNA) molecules, which contain information required to make proteins. Another type of gene encodes ribosomal RNA (rRNA) molecules. Ribosomal RNA forms part of ribosomes, complex RNA-protein particles in the cytoplasm that assemble proteins according to the directions carried in mRNA molecules. The regions of the chromosomes active in making rRNA are collected into structures called nucleoli. Within nucleoli, rRNAs are assembled with proteins into subunits of ribosomes.

The cytoplasm surrounding the nucleus is packed with ribosomes and a variety of organelles. The boundary membranes of the organelles set them off as distinct chemical and molecular environments, specialized to carry out different functions. Ribosomes may be either freely suspended in the cytoplasm or attached to the surfaces of a system of flattened, membranous sacs called the endoplasmic reticulum. Freely suspended ribosomes make proteins that enter the cytoplasmic solution as enzymes, structural supports, or motile elements. Ribosomes attached to the endoplasmic reticulum assemble proteins that become part of membranes or eventually enter small, membrane-bound sacs for storage or release to the cell exterior.

Proteins made in the rough endoplasmic reticulum—those sacs with ribosomes—are modified chemically in another system of membranous sacs, the Golgi complex or apparatus. This system usually appears as a cup-shaped stack of flattened, ribosome-free sacs. The modifications carried out in the Golgi complex may include the addition of chemical groups such as sugars, and the clipping of surplus segments from proteins. Following modification, proteins are sorted into small, membrane-bound sacs that pinch off from the Golgi membranes. These sacs may be stored in the cytoplasm or may release their contents to the cell exterior.

One type of membrane-bound sac containing stored proteins, the lysosome, is particularly important to cell function. Lysosomes contain a group of enzymes collectively capable of breaking down all major molecules of the cell. Many substances taken into cells are delivered to lysosomes, where they are digested by the lysosomal enzymes. Lysosomes may also release their enzymes into the cytoplasm or to the cell exterior. Release within the cell causes cell death, which may occur due to pathological conditions or as part of normal development.

Most of the chemical energy required for cellular activities is produced by reactions taking place in another cytoplasmic organelle, the mitochondrion. Mitochondria
are surrounded by two separate membranes, one enclosed within the other. Within mitochondria occur most of the oxidative reactions that release energy for cellular activities. Fuel for these reactions is provided by the breakdown products of all major cellular molecules, including carbohydrates, fats, proteins, and nucleic acids.

The oxidative functions of mitochondria are supplemented by the activities of peroxisomes (also called microbodies). These structures, which consist simply of a boundary membrane surrounding a solution of enzymes, carry out reactions that link major oxidative pathways occurring elsewhere in the cytoplasm. Microbodies are particularly important to the oxidation of fatty acids.

Almost all cell movements are generated by one of two cytoplasmic structures, microtubules or microfilaments. Microtubules form the motile elements of sperm
tails; microfilaments are responsible for the movements of skeletal, cardiac, and smooth muscle. Microtubules are fine, hollow cylinders about 25 nanometers in diameter, assembled from subunits of a protein known as tubulin. Microfilaments are thin, solid fibers 5 to 7 nanometers in diameter, assembled from subunits of a different protein, actin. Both structures produce motion through protein cross-bridges that work as transducers converting chemical energy to mechanical energy. One end of a cross-bridge attaches to the surface of a microtubule or microfilament; the opposite, reactive end attaches to another microtubule or microfilament or to other cell structures. The cross-bridge produces motion by making an attachment at its reactive end, forcefully swiveling a short distance, and then releasing. Distinct proteins form the swiveling cross-bridges for the two motile elements.

In addition to their functions in cell motility, both microtubules and microfilaments form supportive networks inside cells collectively called the cytoskeleton. Another group of supportive fibers with diameters averaging about 100 nanometers, the intermediate filaments, also forms parts of the cytoskeleton. Intermediate filaments assemble from a large family of related proteins that is distinct from the tubulins and actins forming microtubules and microfilaments.

Disorders and Diseases

Because cell structure and function underlie the totality of bodily functions, all aspects of health and disease reflect normal and abnormal cellular activities. Perhaps the most critical and important of these activities to contemporary medical science is the conversion of normal cellular activity to abnormal activity, which is responsible for cancer. Cancer occurs when cells grow and divide uncontrollably, break free from their normal cell contacts, and migrate to other regions of the body.

The cell transformations occurring in the development of cancer involve changes at several levels. Most of these changes reflect an alteration of one or more genes in the cell nucleus from normal to aberrant forms called oncogenes. Most oncogenes encode proteins involved in a relatively small number of activities. These include nonhistone proteins regulating gene activity, growth hormones, receptors in the plasma membrane for peptide hormones, and proteins taking part in internal cellular response systems triggered by receptors. Directly or indirectly, the altered proteins encoded in oncogenes induce internal changes that lead to uncontrolled cell division and loss of normal adhesions to neighboring cells.

For example, the oncogene
src encodes a protein that adds phosphate groups to other proteins as a cellular control measure. In many types of cancer cells, the src gene or its product is hyperactive. One of the targets of the enzyme encoded in the gene is a receptor protein of the plasma membrane. In some cancer cells, uncontrolled addition of phosphate groups to the receptor causes it to lose its attachment to extracellular structures that hold the cells in place. This loss contributes to the tendency of tumor cells to break loose and migrate to other parts of the body.

In some cases, movement of DNA segments from one chromosome to another is involved in the transformation of cells from normal to cancerous types, including several types of leukemia. For example, in some types of leukemia, breaks occur in chromosomes 8 and 14 in cell lines producing leukocytes, and segments are exchanged between the chromosomes. The exchange moves the gene myc from its normal location in chromosome 8 to a region of chromosome 14 that encodes a major segment of antibody proteins. In its normal location, the myc gene encodes a chromosomal regulatory protein that controls genes involved in cell division. When translocated to chromosome 14, myc comes under the influence of DNA sequences that promote the high activity of the antibody gene. As a result, myc becomes hyperactive in triggering cell division and contributes to the uncontrolled division of white blood cells characteristic of leukemias.

Alterations in cytoplasmic organelles are also directly responsible for some human diseases. The enzymes contained in lysosomes are abnormally secreted in many human diseases. The degenerative changes of arthritis, for example, are suspected to be caused in part by the abnormal release of enzymes from the lysosomes of bone or lymph cells into the fluids that lubricate joints. Some of the damage to lung tissues caused by the inhalation of silica fibers in silicosis is also related to lysosomal function. Microscopic silica fibers are taken in by macrophages and other cells in the lungs; these fibers are delivered to lysosomes for breakdown, as are many other substances. The fibers accumulate in the lysosomes, causing lysosomal enlargement and eventually breakage, causing the destructive release of lysosomal enzymes into the cytoplasm. Other human diseases related to lysosomes are caused by inherited mutations that destroy the activity of lysosomal enzymes. For example, an inherited deficiency in one lysosomal enzyme, hexosaminidase, interferes with reactions clipping carbohydrate segments from molecules removed from the cell surface. As a result, the subparts of these molecules accumulate in lysosomes and cannot be recycled. Their concentration on cell surfaces is diminished; loss of these molecules from nerve cells, particularly a group called gangliosides, can lead to seizures, blindness, loss of intellect, and early death.

Human disease has also been linked to inherited changes in mitochondria. The mutations interfere with the oxidative reactions inside the organelle or have detrimental effects on the transport of substances through the mitochondrial membranes. The mutations cause the most severe problems in locations where the energy supplied by mitochondria is highly critical, particularly in the central nervous system and skeletal and cardiac muscle. Mitochondrial deficiencies in these locations are typically responsible for symptoms such as muscular weakness, irregularities in the heartbeat, and epilepsy.

Deficiencies in motile systems based on microtubules and microfilaments are also associated with human disease. For example, a group of inherited defects known as the immotile cilia or Kartagener’s syndrome is characterized by acute bronchitis, sinusitis, chronic headache, male sterility, and reversal of the position of the heart from the left to the right side of the body. In individuals with the disease, the cyclic cross-bridges driving microtubule-based motion are missing. Male sterility results from loss of motility by sperm tails; other deficiencies result from the immotility of cilia on cells lining the respiratory system and the cavities of the brain. (Cilia are microtubule-based cellular appendages that beat like sperm tails to maintain the flow of fluids over cell surfaces.) In the respiratory system, loss of ciliary beating stops the flow of mucus that normally removes irritating and infectious matter from the lungs and respiratory tract. This deficiency explains the sinusitis and bronchitis. Presumably, an insufficient flow of fluids in the ventricles of the brain, normally maintained by ciliated cells lining these cavities, produces the headaches. The reversed position taken by the heart remains unexplained.

Even the cytoskeleton has been associated with human disease. For example, deficiencies in intermediate filaments of the cytoskeleton have been implicated in the hereditary disease epidermolysis bullosa. In this disease, skin cells are fragile, and slight abrasions that would cause little or no problem in normal individuals lead to severe blistering, ulceration, and scarring.

Perspective and Prospects

Knowledge of cell structure and function developed gradually from the first morphological descriptions of cells in the seventeenth century. By the 1830s, enough information had accumulated for Theodor Schwann and Matthias Schleiden to propose that all living organisms are composed of one or more cells and that cells are the minimum functional units of living organisms. Their conclusions were supplemented in 1855 by a third postulate by Rudolf Virchow: that all cells arise only from preexisting cells by a process of division. Further work established that the cell nucleus contains hereditary information and that the essential feature of cell division is transmission of this information from parent to daughter cells.

The study of cell chemistry and physiology began in the late eighteenth and early nineteenth centuries. By the end of the nineteenth century, investigators had isolated, identified, and synthesized many organic substances found in cells and worked out the structural components of proteins and nucleic acids. This chemical work was complemented by biochemical studies leading to the discovery of enzymes. The gradual integration of cell structure, physiology, and biochemistry continued; by the 1930s, the field had shifted from morphological observations to biochemical and molecular studies of cell function. Crucial to this shift was the research of George Beadle and Edward Tatum, who concluded from their studies that mutant genes encode a faulty form of an enzyme necessary to produce a substance needed for normal growth. On this basis, they proposed that each gene codes for a single enzyme—the famous “one gene–one enzyme” hypothesis.

Further biochemical work revealed the oxidative reactions providing chemical energy for cell activities. This research was integrated with structural studies of cytoplasmic organelles by Albert Claude, who developed a technique for isolating and purifying cell parts by cell fractionation and centrifugation. Claude and his associates successfully isolated ribosomes, endoplasmic reticulum, Golgi complexes, lysosomes, microbodies, and mitochondria by these methods, which allowed biochemical analysis of the fractions. This work was facilitated by development of the electron microscope, allowing elucidation of the ultrastructure of many of the organelles studied biochemically in cell fractions.

Experiments in the 1940s implicating DNA as the hereditary molecule sparked an intensive effort to work out the three-dimensional structure of this molecule, culminating in the discovery of DNA's double-helix structure in 1953 by James D. Watson and Francis Crick. Their discovery led to an effort to determine the molecular structure of genes and their modes of action, which was greatly facilitated by the development of rapid methods for nucleic acid sequencing. Using these methods, many genes have been completely sequenced; the sequences, in turn, allowed deduction of the amino acid sequences of many proteins. The comparisons of gene and protein sequences and structure in normal and mutant forms made possible by these developments provided fundamental insights into the mechanisms controlling and regulating genes and the molecular functions of proteins, revolutionizing biology and medicine.

Bibliography

Alberts, Bruce, et al. Molecular Biology of the Cell. 5th ed. New York: Garland, 2008.

Reece, Jane B., et al. Campbell Biology: Concepts and Connections. 7th ed. San Francisco: Pearson/Benjamin Cummings, 2011.

Karp, Gerald. Cell and Molecular Biology: Concepts and Experiments. 7th ed. Hoboken: Wiley, 2013.

Kindt, Thomas J., Richard A. Goldsby, and Barbara A. Osborne. Kuby Immunology. 7th ed. New York: W. H. Freeman, 2013.

Lewin, Benjamin. Genes IX. 9th rev. ed. Sudbury, Mass.: Jones and Bartlett, 2008.

Lodish, Harvey, et al. Molecular Cell Biology. 7th ed. New York: W. H. Freeman, 2012.

Rasmussen, Nicolas. Picture Control: The Microscope and the Transformation of Biology in America, 1940–1960. Stanford, Calif.: Stanford University Press, 1997.

Stipp, David. "Quiet Little Traitors." Scientific American 307.2 (2012): 68–73.

Wolfe, Stephen L. Molecular and Cellular Biology. Belmont, Calif.: Wadsworth, 1993.

What are some good topics to do a Macbath essay on?

You might consider addressing Macbeth's tragic flaw. You could make an argument that identifies his tragic flaw and then defends it. There are several contenders.  First, his ambition is a possibility. Lady Macbeth first identifies Macbeth as ambitious when she receives his letter (1.5.19). She knows he's ambitious but fears that he won't "catch the nearest way" to the throne (1.5.17).  Then, Macbeth identifies his one reason to go ahead with Duncan's murder as his...

You might consider addressing Macbeth's tragic flaw. You could make an argument that identifies his tragic flaw and then defends it. There are several contenders.  First, his ambition is a possibility. Lady Macbeth first identifies Macbeth as ambitious when she receives his letter (1.5.19). She knows he's ambitious but fears that he won't "catch the nearest way" to the throne (1.5.17).  Then, Macbeth identifies his one reason to go ahead with Duncan's murder as his "Vaulting ambition," after he's outlined the many reasons he has not to go through with it (1.7.27).  Second, it could be his pride that is his tragic flaw.  Right after Macbeth identifies his ambition, he decides not to go forward with the crime (1.7.34).  It is not until Lady Macbeth wounds his pride, calling him a "coward" that he relents and recommits to their plan (1.7.47).  

You could also consider identifying Macbeth's foil and making an argument that consists of the traits possessed by Macbeth that are illuminated by his contrast with his foil.  A "foil" is a character that highlights some attributes of the protagonist (usually) through contrast.  So, Banquo could be a foil for Macbeth: he doubts the sincerity of the Weird Sisters (1.3.134-138) while Macbeth (perhaps gullibly) believes them completely (1.3.157-159).  He also remains loyal to Duncan, showcasing Macbeth's terrible disloyalty. Further, Banquo is honest, and Macbeth's ability to lie only gets stronger and stronger. You might also consider Lady Macbeth as a foil for Macbeth.  She begins the play as a ruthless, murderous, guiltless villain; though, by the plays end, she's descended into a madness brought on by her terrible guilt.  She emphasizes Macbeth's opposite trajectory. He starts off as the one who is guilt-ridden and fearful, but he quickly becomes even more murderous and merciless than Lady Macbeth ever was as the play progresses.  

What is clinical supervision? |

Clinical supervision is a formal relationship in which a more experienced member of a profession provides oversight and guidance to a junior member of the same profession. Most clinical supervisory relationships occur between individuals who work for the same organization. Clinical supervision is mostly used in the fields of mental health counseling, substance abuse counseling, and psychotherapy.

The clinical supervisor's goal is to help less experienced supervisees develop into well-rounded, effective practitioners. Supervisors should help supervisees to develop needed skills to work in appropriate fields. The supervisees should be able to learn from their own experiences during the clinical supervision.

Supervisory Relationships

Once a supervisory relationship is established, clinical supervisors meet regularly with their supervisees over an extended period. The purpose of these meetings is for the supervisor to evaluate how the supervisee is performing, monitor the quality of services being offered, and provide professional support and guidance. Clinical supervisors also play a crucial role in helping supervisees to develop and maintain strong medical ethical standards. Effective clinical supervisors are knowledgeable, competent, skilled, and appropriately credentialed as both counselors and supervisors. Credentialing requirements vary by profession and state.

Clinical supervisors work closely with their supervisees to ensure that the supervisees are capable of offering the best possible care to clients. Supervisors focus on developing strong, positive relationships with their supervisees. They promote professional development by helping supervisees to develop a greater degree of self-awareness, make connections between theory and practice, obtain a stronger foundation of clinical knowledge, and improve functional skills. Clinical supervisors play four key roles with supervisees: teacher, coach, mentor, and consultant.

Teacher

Clinical supervisors act as teachers, or those who provide education, to their supervisees by promoting the continual refinement of professional knowledge and skills. They may work with supervisees to identify specific developmental needs and make recommendations for how these needs can be addressed. For example, counseling supervisors may share their own knowledge and experience about specific cases with supervisees as a way to show how a problem could be resolved. Alternately, supervisors may recommend that the supervisee review certain learning materials, take additional courses with local educational institutions, or even pursue a particular certification.

Coach

Clinical supervisors act as coaches, or ones who offer support, to their supervisees in a number of ways. First, they may encourage their supervisees by affirming the clinical choices and approaches made by the supervisees. Supervisors may work on building supervisees' self-confidence so that the supervisees begin to trust their intuition when interacting with clients. They may even act as "cheerleaders" to help less experienced supervisees feel more supported and assured in their work.

Mentor

Clinical supervisors act as
mentors
, individuals who offer advice and guidance, by offering feedback and professional counseling on professional issues. They may spend session time discussing the clinical choices made by the supervisees. Supervisors also may offer alternative viewpoints to help the supervisees see clients or issues in different ways.

Consultant

Supervisors act as consultants, or experts about a certain subject, because they have expertise in their field. As consultants, supervisors carefully review the progress and outcomes of supervisees' clients to monitor how supervisees are performing and to determine how clients are progressing under the care of the supervisees. Supervisors may offer feedback on individual cases to guide the supervisees toward the best possible path to take to get the greatest outcomes with clients. They may make recommendations and suggestions to supervisees about ways to adjust treatment plans for clients.

Clinical supervisors also may play a larger consulting role at a specific organization. They may act as the organization's "gatekeepers" to ensure staff are performing to the level required and clients are receiving the best and most appropriate treatment. Clinical supervisors may be expected to make recommendations for discipline if supervisees make poor choices or consistent errors.

Benefits

Clinical supervision has many benefits for supervisors, supervisees, and the organization for which they work. Some of these benefits include the following:

• Supervisees have a strong, ongoing support network. They are able to speak directly to one or more senior professionals regarding their work as well as discuss any issues they are experiencing with clients or the organization.




• The quality and level of clinical skills in the organization tends to steadily increase. Additionally, supervisees typically gain more complex clinical skills over time as they receive feedback from supervisors and are guided in their professional development.




• Because all an organization's staff members are required to participate in clinical supervision, performance across the organization becomes more standardized, which is shown to have a positive effect on clients.




• Staff members at all levels tend to feel more satisfied with their jobs. This may be due to a number of factors, including the high degree of communication promoted by the clinical supervisory relationship as well as a feeling of connection with others. Employees satisfied with their jobs usually have higher morale and a longer tenure with an organization, creating a more stable environment for both clients and other employees.




• Client outcomes tend to improve because more professionals are participating in their cases.

Bibliography

"Clinical Supervision and Professional Development of the Substance Abuse Counselor." National Center for Biotechnology Information. National Center for Biotechnology Information, U.S. National Library of Medicine. Web. 27 Jan 2015. http://www.ncbi.nlm.nih.gov/books/NBK64848/

"Models of Clinical Supervision." Addiction Messenger. Northwest Frontier ATTC 8.10 (2005). Web. 27 Jan 2015. https://www.unodc.org/ddt-training/treatment/VOLUME%20D/Topic%202/3.1-Models_of_Clinical_Supervision.pdf

"Workforce Development 'TIPS.'" Australia's National Research Centre on Alcohol and Other Drugs Workforce Development. Alcohol Education and Rehabilitation Foundation Ltd (AER). 2005. Web. 27 Jan 2015. https://www.unodc.org/ddt-training/treatment/VOLUME%20D/Topic%202/8.Workforce%20Development%20TIPS.pdf

Think about the role of weather in the novel. How does it work, symbolically or otherwise, in relation to important elements of the novel such as...

Rain and drought play significant roles at a specific, strategic point in Chinua Achebe’s Things Fall Apart. Indeed, Achebe potently uses rain and drought to symbolize and foreshadow Okonkwo’s life in one specific instance early in the novel.  Okonkwo reflects on a devastating yam harvest that almost ruined him:

“The year that Okonkwo took eight hundred seed-yams from Nwakibie was the worst year in living memory. Nothing happened at its proper time; it was...

Rain and drought play significant roles at a specific, strategic point in Chinua Achebe’s Things Fall Apart. Indeed, Achebe potently uses rain and drought to symbolize and foreshadow Okonkwo’s life in one specific instance early in the novel.  Okonkwo reflects on a devastating yam harvest that almost ruined him:

“The year that Okonkwo took eight hundred seed-yams from Nwakibie was the worst year in living memory. Nothing happened at its proper time; it was either too early or too late. It seemed as if the world had gone mad. The first rains were late, and, when they came, lasted only a brief moment. The blazing sun returned, more fierce than it had ever been known, and scorched all the green that had appeared with the rains. The earth burned like hot coals and roasted all the yams that had been sown” (23).

 After his initial crops fail because of an intense drought, Okonkwo is slightly relieved that he had borrowed seeds from another man early in the harvest, and decides to plant those to supplant his tremendous losses. However, instead of a drought, an abundance of rain washes away the crops:

“Rain fell as it had never fallen before. For days and nights together it poured down in violent torrents, and washed away the yam heaps.... The yams put on luxuriant green leaves, but every farmer knew that without sunshine the tubers would not grow. That year the harvest was sad, like a funeral.... One man tied his cloth to a tree branch and hanged himself. Okonkwo remembered that tragic year with a cold shiver throughout the rest of his life” (24).

This passage is symbolic because it foreshadows the trajectory of Okonkwo’s life. Nothing happens when it is supposed to, and he perceives that he suffers because of the whims of the gods. Additionally, the man who hangs himself portends Okonkwo’s own suicide.

What is dengue fever? |

Causes and Symptoms

Although dengue fever is primarily confined to the tropics, each year it causes nearly four hundred million infections worldwide. Dengue is caused by the dengue virus (DENV) that belongs to the Flaviviridae family. This viral family includes several other members, such as the yellow fever
virus and the West Nile
encephalitis
virus, all of which have emerged as serious public health concerns over the years. All four serotypes of dengue virus (DENV-1 through DENV-4) are capable of causing the full spectrum of clinical manifestations, from asymptomatic presentation to dengue fever to the more severe dengue hemorrhagic fever or dengue shock syndrome. These forms are primarily found in hyperendemic areas that have all four serotypes of dengue virus.

Dengue virus enters the human host via the bite of an infected Aedes mosquito, primarily A. aegypti and occasionally A. albopictus. These vector populations are difficult to control because they are highly invasive and over time have accumulated adaptations that make them extremely resilient. Once inside the Aedes mosquito, having entered it via a blood meal, the dengue virus needs to incubate for about eight to twelve days in the mosquito before it can initiate another round of infection in a healthy host. An Aedes mosquito that has acquired the dengue virus will forever act as a vector.

After being bitten by the infected Aedes mosquito, a human host will typically start showing symptoms anywhere between four to seven days; symptoms last for as long as three to ten days. Once inside the human body, the dengue virus first replicates inside the dendritic cells. The replicated virus then infects macrophages and lymphocytes before entering the patient’s bloodstream. Dengue fever patients can show a variety of symptoms, from mild feverishness to high fever of abrupt onset along with severe headache, pain behind the eyes (retro-orbital pain), flushing of the face, malaise, generalized joint and muscle pains, nausea, vomiting, and rash.

In dengue hemorrhagic fever and dengue shock syndrome, the more severe forms of dengue, clinical manifestations include fever, hemorrhage (diagnosed with a tourniquet test), low platelet count (thrombocytopenia), and increased vascular permeability. Some signs of hemorrhage seen in dengue hemorrhagic fever patients include pinpoint-sized red dots (petechiae), fragile capillaries that could lead to passage of blood from the ruptured blood vessels into subcutaneous tissue (purpura), and blood stains in vomit and stool (melena). The severity of dengue hemorrhagic fever depends on the extent of plasma leakage (detected by a rise in hematocrit level) from the capillaries that results in hypovolemia. As plasma continues to leak into the interstitial spaces, the patient can go into hypovolemic shock, a situation that can be fatal. These symptoms are typically accompanied by liver failure and increase in liver size (hepatomegaly). Concomitantly, as one would expect, viremia titers (indicating the presence of virus in the bloodstream) are much more pronounced in cases of dengue hemorrhagic fever and dengue shock syndrome as compared to dengue fever.

Clinical diagnosis of dengue virus infection is based on signs of leukopenia (low white blood cell count), thrombocytopenia, and high serum transaminase levels in blood tests. Since rash is a common component of dengue fever, often the extent, nature, and location of the rash is used in the diagnostic process—for example, dengue rash is usually seen on the trunk and inner surfaces of the thighs and arms. With an increase in number of dengue cases, some unusual neurological complications, such as convulsions, spasticity, and encephalopathy (resulting from water intoxication), have also been reported. To date, the exact molecular mechanism that underlies the pathogenesis seen in dengue hemorrhagic fever and dengue shock syndrome is not very well understood and is still under investigation.

Treatment and Therapy

Patients who have been diagnosed with dengue virus infection are required to maintain adequate hydration levels. Often, the key to successful management of a patient with dengue hemorrhagic fever or dengue shock syndrome involves a careful monitoring of the patient’s fluid level and replenishing any deficits with isotonic solution administered intravenously. Antipyretics such as acetaminophen are used for pain and fever management; patients are advised to avoid using aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), since they may accentuate the bleeding problem associated with certain types of dengue infection. Blood transfusions and oxygen therapy may also be used to treat dengue hemorrhagic fever.

The adaptive immune response of the patient plays an important role in clearing of the infection as well as providing immunity against reinfection. Infection with a DENV serotype (1–4) protects the individual only against reinfection by the same serotype. Since there are four serotypes of dengue virus, in theory, a person can get dengue as many as four times during his or her lifetime. Efforts are underway to design a vaccine; the ideal vaccine would provide lifelong protection against all four DENV serotypes. Dengue vaccine candidates that are currently being investigated include live attenuated vaccines, inactivated virus vaccines, recombinant subunit vaccines, and deoxyribonucleic acid (DNA) vaccines.

Perspective and Prospects

Dengue is considered an emerging infectious disease. As with the Ebola virus, the four serotypes are believed to have originated in monkeys in Africa or Southeast Asia and then mutated to move on to the human host several hundred years ago. Until the mid-twentieth century, dengue was largely a localized infection, primarily affecting populations in Southeast Asia. It is believed that the spread of the Aedes mosquito vector, and thus the dengue virus pathogen, via cargo ships to different parts of the world contributed to the global threat that the world is currently experiencing. Approximately 3.9 billion people in 128 countries are now at risk of infection with the dengue virus. Nearly 2.4 million cases are reported annually, but the disease is thought to be underreported, and the actual number is estimated to be closer to 390 million. In 2010, local transmission of the dengue virus within Europe was reported for the first time, and in 2012 there was an outbreak on the Madeira islands of Portugal that resulted in a number of cases being imported to mainland Portugal and elsewhere in Europe. In 2013 there was an outbreak in Laos and an increase in cases in Singapore, and several South American countries, primarily Costa Rica, Honduras, and Mexico, were badly affected by the virus. Cases were also reported in Florida that year. In 2014 cases increased throughout the Pacific Islands and in China, and Japan recorded its first cases of dengue in over seventy years. Countries particularly affected in 2015 include Brazil, Fiji, Tonga, and French Polynesia. In addition, cases increased 35 percent in Taiwan between 2014 and 2015, and India had its worst outbreak in years.

Bibliography

Carson-DeWitt, Rosalyn. "Dengue Fever." Health Library. EBSCO Information Services, 30 Dec. 2011. Web. 5 Oct. 2015.

"Dengue." Centers for Disease Control and Prevention. CDC, 15 June 2015. Web. 5 Oct. 2015.

"Dengue and Severe Dengue." World Health Organization. WHO, May 2015. Web. 5 Oct. 2015.

"Dengue Fever." MedlinePlus. Natl. Lib. of Medicine, 11 Jan. 2013. Web. 5 Oct. 2015.

"Dengue Hemorrhagic Fever." MedlinePlus. Natl. Lib. of Medicine, 10 Nov. 2012. Web. 5 Oct. 2015.

"Drug Treatment Hope for Dengue Fever after Research Breakthrough." Guardian. Guardian News and Media, 10 Sept. 2015. Web. 5 Oct. 2015.

Halstead, S. B. “More Dengue, More Questions.” Emerging Infectious Diseases 11.5 (2005): 740–741. Print.

Hirshler, Ben. "Experts Triple Estimate of World Dengue Fever Infections." Reuters.. Reuters, 7 Apr. 2013. Web. 5 Oct. 2015.

Senthilingam, Meera. "Dengue Fever: How a Mosquito Infected Millions, and Not with Malaria." CNN. CNN, 2 Sept. 2015. Web. 5 Oct. 2015.

Whitehead, S. S., et al. “Prospects for a Dengue Virus Vaccine.” Nature Reviews Microbiology 5 (2007): 518–28. Print.

What is phenobarbital? How does it interact with other drugs?

Folate

Effect: Supplementation Possibly Helpful

Phenobarbital can reduce folate levels, perhaps by increasing the rate of
breakdown of the vitamin. Over time, such a decrease can cause anemia.
Taking folate supplements can correct this anemia.
Anticonvulsant-induced folate deficiency might also cause birth defects. Women who
plan to become pregnant while on phenobarbital should be sure to take a supplement
to prevent deficiency.

Vitamin D

Effect: Supplementation Possibly Helpful

Phenobarbital appears to interfere with the normal absorption or metabolism of
vitamin
D. In turn, this can impair calcium absorption. Making sure
to get enough vitamin D (and calcium) should help prevent any problems from
developing.

Vitamin K

Effect: Supplementation Helpful for Pregnant Women

Children born to women taking phenobarbital while pregnant may be deficient in
vitamin
K. This might lead to bleeding disorders and facial bone
abnormalities. Supplementing with vitamin K during pregnancy should help; however,
physician supervision is recommended.

Biotin

Effect: Supplementation Possibly Helpful, but Take at a Different Time of Day

Many antiseizure medications, including phenobarbital, are believed to interfere
with the absorption of biotin. For this reason, persons taking
phenobarbital may benefit from extra biotin. Biotin should be taken two to three
hours apart from antiseizure medication. One should not exceed the recommended
daily intake, because it is possible that too much biotin might interfere with the
effectiveness of the medication.

Dong Quai, St. John’s Wort

Effect: Possible Harmful Interaction

Phenobarbital has been reported to cause increased sensitivity to the sun,
amplifying the risk of sunburn or skin rash. Because St. John’s
wort and dong quai may also cause this problem,
taking them during treatment with this drug might add to this risk. One should use
sunscreen or wear protective clothing during sun exposure if taking one of these
herbs while using this anticonvulsant.

Ginkgo

Effect: Possible Harmful Interaction

The herb ginkgo (Ginkgo biloba) has been used to
treat Alzheimer’s disease and ordinary age-related memory loss, among many other
conditions. The possible harmful interaction involves potential contaminants in
ginkgo, not ginkgo itself.

One study found that a natural nerve toxin present in the seeds of Ginkgo biloba made its way into standardized ginkgo extracts prepared from the leaves. This toxin has been associated with convulsions and death in laboratory animals.

The detected amounts of this toxic substance are considered harmless. However, given the lack of satisfactory standardization of herbal formulations in the United States, it is possible that some batches of product might contain higher contents of the toxin, depending on the season of harvest. In light of these findings, taking a ginkgo product that happened to contain significant levels of the nerve toxin might theoretically prevent an anticonvulsant from working as well as expected.

Hops, Kava, Passionflower, Valerian

Effect: Possible Harmful Interaction

The herb kava (Piper methysticum) has a sedative
effect and is used for anxiety and insomnia. Combining kava with anticonvulsants,
which possess similar depressant effects, could result in add-on or excessive
physical depression, sedation, and impairment. Because of the potentially serious
consequences, one should avoid combining these herbs with anticonvulsants or other
drugs that also have sedative or depressant effects, such as phenobarbital, unless
advised by a physician.

Glutamine

Effect: Theoretical Harmful Interaction

Because phenobarbital works (at least in part) by blocking glutamate pathways in
the brain, high dosages of glutamine might possibly overwhelm the
drug and increase the risk of seizures.

Bibliography

Arenz, A., et al. “Occurrence of Neurotoxic 4’-O-Methylpyridoxine in Ginkgo biloba Leaves, Ginkgo Medications, and Japanese Ginkgo Food.” Planta Medica 62 (1996): 548-551.

Cornelissen, M., et al. “Supplementation of Vitamin K in Pregnant Women Receiving Anticonvulsant Therapy Prevents Neonatal Vitamin K Deficiency.” American Journal of Obstetrics and Gynecology 168 (1993): 884-888.

Kishi, T., et al. “Mechanism for Reduction of Serum Folate by Antiepileptic Drugs During Prolonged Therapy.” Journal of the Neurological Sciences 145 (1997): 109-112.

Lewis, D. P., et al. “Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes: Part I–Antiepileptic Drugs, Contraceptives, Smoking, and Folate.” Annals of Pharmacotherapy 32 (1998): 802-817.

For the book The Help, what is a one-paragraph summary of Chapter 27?

A lot happens here, as many threads of the story reach their tipping points. The chapter is told by Miss Skeeter, beginning on December 2. She learns that the publisher’s deadline for the manuscript is December 21, and not in January, as she had thought. And the editor wants to include Constantine’s story. Skeeter and Aibileen will have to hustle to get the work done. They decide on “Help” as the title. Aibileen finally shares...

A lot happens here, as many threads of the story reach their tipping points. The chapter is told by Miss Skeeter, beginning on December 2. She learns that the publisher’s deadline for the manuscript is December 21, and not in January, as she had thought. And the editor wants to include Constantine’s story. Skeeter and Aibileen will have to hustle to get the work done. They decide on “Help” as the title. Aibileen finally shares Constantine’s history and fate with Skeeter. And after some discussion and thought, they decide to include Minny’s “Terrible Awful” story in the book, for insurance purposes against Hilly Holbrook’s retribution. In the meantime, Skeeter loses her newsletter position with the Jackson Junior League, due mostly to her disintegrating relationship with Hilly. Stuart visits Longleaf, and Skeeter asks him to leave. She confronts her own mother about firing Constantine. Now that she knows all sides of that situation, she can write about it. Skeeter works diligently and takes the finished manuscript to the post office, only to get there after the truck has left for the day. She hopes it reaches the publisher in time. 

What are clinical trials? |

Indications and Procedures

Clinical trials offer the most reliable process for bringing new drugs and medical treatments into public use. The process has features that can protect human participants, avoid biases, ensure that patient improvements are due to the experimental treatment and not to other factors, and allow accurate comparison of the experimental treatment with others on the market. Clinical trials are usually initiated and managed by academic institutions (often with grant funding), pharmaceutical companies, or government research agencies, such as the National Cancer Institute.

In 1998, it was estimated that the cost of developing a new drug was, on average, $500 million, and the process could take twelve to fifteen years—from discovery and laboratory testing, through clinical trials, to Food and Drug Administration (FDA) approval, and finally getting the drug to market. By the late 1990s, a new drug might go through sixty-eight clinical trials. The average number of patients enrolled in a trial was 3,800.

Clinical trials fit into one of four types. Phase I trials, which usually involve only twenty to one hundred seriously ill patients, try to determine how to administer a new drug, the maximally tolerated dose (MTD), how the human body processes the drug, and any significant side effects. Phase II trials, which are usually randomized, treat up to several hundred patients who all have measurable rates of disease. These trials study the effectiveness of the drug. Phase III trials, which are usually randomized and blinded and which treat hundreds or thousands of patients, have more relaxed criteria for inclusion and are usually multicenter (held simultaneously at more than one site). These trials try to determine whether the new drug is better than current, standard ones. Phase IV trials, conducted once a drug is on the market, are often informal. Pharmaceutical companies may simply ask physicians to submit reports on how their patients are responding to the drug.

Uses and Complications

The 1979 Belmont Report detailed three ethical principles to guide clinical trials. They include respect for persons (abiding by their opinions and choices as autonomous agents), beneficence (doing no harm and maximizing the possible benefits while minimizing possible harm), and justice (distributing the benefits and burdens of research fairly).

Two standard features of clinical trials help ensure that ethical principles are being followed. First, all clinical trials in the United States must be approved and monitored by an Institutional Review Board (IRB), which includes both scientists and laypersons. Multicenter trials must also have a data safety and monitoring board composed of independent experts. This group monitors data from the trial regarding the treatment’s effectiveness and any adverse reactions. Second, the detailed informed consent document that patients must carefully consider and sign gives a number of categories of information. Most important, anticipated physical risks and discomforts are explained, as are financial risks. Similar practices are followed in countries other than the United States as well.

Perspective and Prospects

In October, 1948, The British Medical Journal published an article reporting on what was probably the first study using all the methodological features of the randomized clinical trial. Since then, the randomized clinical trial has come to be regarded as perhaps the most important medical achievement of the twentieth century. It transformed biomedical research and allowed physicians to make treatment choices based on scientific evidence rather than on personal opinion and experience.

The National Cancer Institute (NCI)
and other sources reported a small participation rate in clinical trials—ranging in the late 1990s from 3 to 20 percent of patients. One of many causes was that insurance companies and managed care providers frequently refused payment for experimental treatments. Their concerns were that they might be liable for adverse reactions or additional care after the trial ends and that clinical trials are more costly than conventional treatments. Because so many insurers would not cover the costs of clinical trials, researchers had trouble finding patients willing to participate, thus slowing the development of more effective drugs and treatments. Insurers gradually realized that more widespread coverage of the costs of trials might speed the development of better drugs, which could ultimately save them money. In 1998, US states began to pass laws requiring insurers to cover the routine medical costs (such as tests and office visits) of treatment in clinical trials of drugs for life-threatening diseases.

Criticism has been leveled at clinical trials for insufficient inclusion of women, children, people of color, and the aged. When these groups are underrepresented, there is no certainty that a drug will be effective or without side effects for them.

In June 2000, the FDA added a regulation that would place a clinical hold on a phase I trial of a drug or treatment for a life-threatening disease affecting both women and men if either gender was excluded because of risk to their reproductive potential. That same month, President Bill Clinton signed an executive memorandum directing Medicare to reimburse senior citizens for routine medical costs incurred in clinical trials. A major impetus for this change came from reports that only 33 percent of cancer clinical trial participants were over sixty-five, while 63 percent of all cancer patients are over sixty-five.

Bibliography

Beer, Tomasz M., and Larry Axmaker. Cancer Clinical Trials: A Commonsense Guide to Experimental Cancer Therapies and Clinical Trials. New York: DiaMedica, 2012.

"Clinical Trials." MedlinePlus, May 3, 2013.

"Clinical Trials of Medical Treatments: Why Volunteer?" US Food and Drug Administration, Jan. 4, 2010.

Finn, Robert. Cancer Clinical Trials: Experimental Treatments and How They Can Help You. Sebastopol, Calif.: O’Reilly, 1999.

Green, Stephanie, Jacqueline Benedetti, and John Crowley. Clinical Trials in Oncology. 3d ed. Boca Raton, Fla.: Chapman & Hall, 2012.

Harrington, David P. “The Randomized Clinical Trial.” Journal of the American Statistical Association 95, no. 449 (March, 2000): 312–315.

"Learn about Clinical Studies." ClinicalTrials.gov, Aug 2012.

Malay, Marilyn. Making the Decision: A Cancer Patient’s Guide to Clinical Trials. Sudbury, Mass.: Jones and Bartlett, 2002.

"Overview of Clinical Trials." CenterWatch Clinical Trials Listing Service, n.d.

Quinn, Susan. Human Trials: Scientists, Investors, and Patients in the Quest for a Cure. Cambridge, Mass.: Perseus, 2002.

What is the relationship between panic disorders and addiction?

Background

Panic attacks occur frequently and without warning. They even can begin during sleep. Over time, persons with panic disorder may begin to avoid situations they believe can trigger a panic attack or may, for example, stop leaving their homes because they fear that no place is safe.

Symptoms

People with panic disorder are plagued by feelings of impending doom. The symptoms of panic disorder also include sweating, chest pain or pressure, irregular heartbeat, shortness of breath, a feeling of choking or being smothered, dizziness, a sense of unreality, a tingling sensation in the hands or feet, chills, flushing, nausea, a pressing desire to escape, and difficulty sleeping.

According to the Anxiety Disorders Association of America, approximately 6 million adults in the United States experience panic attacks each year. Women are twice as likely to be affected.

How Panic Disorder Can Lead to Addiction

The symptoms of panic disorder can be extremely uncomfortable and overwhelming, so many people with the disorder turn to drugs and alcohol to relieve their symptoms. This action is known as self-medicating. Central nervous system depressants, such as alcohol, marijuana, and opiates, are commonly used to self-medicate. Long-term use of any of these substances can lead to addiction.

Over time, people who use drugs or alcohol to self-medicate will build up a tolerance to the drug, so that they will eventually need to increase the amount of the substance to get the same effect. For example, a person who may at first be having a drink or two to relax at the end of the day may find that, eventually, three, four, or more drinks are needed to feel relaxed. A person who began taking one pain pill a day to relieve symptoms of panic disorder may need to take two or three pills a day to get the same relief.

Self-medication also can lead to other problems. That is, the relief from self-medicating is temporary, the side effects of long-term drug or alcohol use can be severe, and the underlying cause of the panic disorder is ultimately not treated.

How Addiction Can Lead to Panic Disorder

Panic disorder also can be caused by substance abuse. Certain substances, such as caffeine, tobacco, cocaine, and methamphetamine, can trigger panic attacks. Panic disorder symptoms caused by substance abuse may include irregular heart rate, flushing, dizziness, sweating, and difficulty sleeping. These symptoms can last long after the effects of the drug wear off, which often makes the person want to use the substance again.

Additionally, withdrawal from alcohol or opiates can cause symptoms of panic disorder. Panic disorder symptoms caused by alcohol or opiate withdrawal may include sweating, rapid heartbeat, dizziness, flushing, and difficulty sleeping. Therefore, a person who is self-medicating to avoid symptoms of panic disorder may be increasing his or her risk of a panic attack through substance abuse and subsequent withdrawal.

The Anxiety and Panic Disorder Cycle

Panic disorder and substance abuse often coexist in a vicious cycle. Although central nervous system depressants are often used to relieve panic disorder symptoms, the symptoms of panic disorder escalate when a person discontinues the depressant drugs and experiences withdrawal symptoms. This leads the person with the panic disorder to repeat the self-medicating behavior. When panic disorder is caused by addiction, the panic that is caused by the substance abuse is often further “treated” by using and abusing the substance.

Bibliography

Anxiety Disorders Association of America. “Panic Disorder and Agoraphobia.” ADAA. Anxiety Disorders Assn. of America, n.d. Web. 29 Oct. 2015.

Anxiety Disorders Association of America. “Substance Abuse Disorders.” ADAA. Anxiety Disorders Assn. of America, n.d. Web. 29 Oct. 2015.

Robinson, Jennifer, et al. “Role of Self-medication in the Development of Comorbid Anxiety and Substance Use Disorders: A Longitudinal Investigation.” Archives of General Psychiatry 68.8 (2011): 800–807. JAMA Psychiatry. Web. 29 Oct. 2015.

Smith, John. Co-Occurring Substance Abuse and Mental Disorders: A Practitioner's Guide. Lanham: Rowman, 2007. Print.

Stewart, Sherry H., and Patricia J. Conrod, eds. Anxiety and Substance Use Disorders: The Vicious Cycle of Comorbidity. New York: Springer, 2008. Print.

On the basis of the works of Beowulf, Paradise Lost, Gulliver's Travels, and Heart of Darkness, what view does English literature offer on the...

English literature reflects the view that civilization has declined in its morality over the centuries, even as it's made progress technologically. In Beowulf (written down around 1000 CE), the noble Hrothgar and his well-kept and cheery hall are the only bright spots of civilization in a world that is menaced by monsters like Grendel and hemmed in by darkness. Only the mead-hall where Hrothgar and his community dwell is pleasant because it is a beacon of civilization; the rest of the world is dark and dismal.

Paradise Lost (published in 1667) explains the fall of man that forever tainted civilization. While Adam and Eve were born perfect in God's image, Satan in the form of a serpent duped Eve into tasting fruit from the tree of knowledge. While her hasty decision gave humans more knowledge and perhaps the means to construct a more advanced civilization, humans were forever corrupted. In this epic, civilization is linked to the downfall of man. Human advancement can only be seen as an extension of their corruption.

Gulliver's Travels, published in 1726, is a critique of civilization and its advancement of science. For example, on the island of Laputa, the people work to advance science but can't figure out how to do so with any effective results. They ridiculously devote themselves to experiments such as turning marble into pillows and other pointless efforts that poke fun at the use of science to better society. No matter where Gulliver travels, or what the society is like in that place, it is inherently foolish. Therefore, there is no form of society that is ideal.

Finally, in Heart of Darkness, civilization is totally corrupted. The ivory company that controls the Congo uses technology, such as steamships and guns, to slaughter the local people and extract ivory to make themselves rich. There is nothing redeeming or noble about their technological superiority over the local people. Conrad, who published this novella in 1899, suggests that civilization is bent on evil.

Do you think Mary Maloney really loved her husband Patrick Maloney? Explain why or why not.

I can see this answer going either way, so what is most important is explaining to your teacher why you think what you think.  

Personally, yes, I think Mary Maloney was very much in love with her husband.  I believe that she saw Patrick as the reason for her existence.  He is central to her entire universe.  If this were Romeo and Juliet, Patrick would be the sun in Mary's east. 

When the...

I can see this answer going either way, so what is most important is explaining to your teacher why you think what you think.  

Personally, yes, I think Mary Maloney was very much in love with her husband.  I believe that she saw Patrick as the reason for her existence.  He is central to her entire universe.  If this were Romeo and Juliet, Patrick would be the sun in Mary's east. 

When the story first begins, the reader is introduced to Mary patiently sitting at home doing nothing other than waiting for Patrick to come home.  She continually checks the clock to assure herself that time is continuing to pass, because each moment that does is one more moment closer to Patrick's arrival.  

Now and again she would glance up at the clock, but without anxiety, merely to please herself with the thought that each minute gone by made it nearer the time when he would come.

That sounds very much like she is in love with Patrick.  When he finally does get home, she moves about the room with a singular purpose.  That purpose is to ensure that Patrick is well taken care of.  She greets him at the door, insists that he sit and rest, and quickly serves him his drink.  After that, Mary is joyous to sit within his very presence.  Yes, I believe that Mary loves Patrick a lot. 

She loved to luxuriate in the presence of this man, and to feel-almost as a sunbather feels the sun-that warm male glow that came out of him to her when they were alone together. She loved him for the way he sat loosely in a chair, for the way he came in a door, or moved slowly across the room with long strides. She loved intent, far look in his eyes when they rested in her, the funny shape of the mouth, and especially the way he remained silent about his tiredness, sitting still with himself until the whiskey had taken some of it away.

What is attention-deficit hyperactivity disorder (ADHD)?

Introduction

Attention-deficit hyperactivity disorder (ADHD) is one of the most extensively studied behavior disorders that begin in childhood. Thousands of journal articles, chapters, and books have been published on the disorder. There are a number of reasons this disorder is of such interest to researchers and clinicians. The two primary reasons are that ADHD is a relatively common disorder of childhood (it is regarded as a childhood disorder although it can persist into adulthood) and that there are numerous problems associated with ADHD, including lower levels of intellectual and academic performance and higher levels of aggressive and defiant behavior.

In national and international studies of childhood emotional and behavioral disorders, ADHD has been found to be relatively common among children. Although prevalence estimates range from 1 to 20 percent, most researchers agree that between 3 and 7 percent of children could be diagnosed as having ADHD. The fifth edition of the
Diagnostic and Statistical Manual of Mental Disorders: DSM-5, published by the American Psychiatric Association in 2013, describes the diagnostic criteria for ADHD. To receive the diagnosis of ADHD according to DSM-5, a child must show abnormally high levels of inattention, hyperactivity-impulsivity, or both when compared with peers of the same age. The DSM-5 lists two sets of behavioral symptoms characteristic of ADHD. The first list contains nine symptoms of inattention such as “often has difficulty sustaining attention in tasks or play activities,” while the second list contains nine symptoms of hyperactivity-impulsivity such as “often talks excessively” and “often has difficulty awaiting turn.” To be diagnosed with ADHD, a child must exhibit at least six symptoms from at least one of the lists. Although many of these behaviors are quite common for most children at some point in their lives, the important point to consider in the diagnosis of ADHD is that these behaviors must be in excess of the levels of behaviors most frequently exhibited for children of that age and that the behaviors must cause functional impairment in at least two settings (for instance, at home and at school). Additionally, it is expected that "several inattentive or hyperactive-impulsive symptoms were present prior to age twelve."

Boys tend to outnumber girls in the diagnosis of ADHD, with the male-to-female ratio estimated at 2:1 to 9:1, depending on the source. ADHD boys tend to be more aggressive and antisocial than ADHD girls, while girls are more likely to display inattentive symptoms.

Associated Problems

There are a number of additional problems associated with ADHD, including the greater likelihood of ADHD boys exhibiting aggressive and antisocial behavior. Although some ADHD children do not show any associated problems, many ADHD children show deficits in both intellectual and behavioral functioning. For example, a number of studies have found that ADHD children score an average of seven to fifteen points below normal children on standardized intelligence tests. It may be, however, that this poorer performance reflects poor test-taking skills or inattention during the test rather than actual impairment in intellectual functioning. Additionally, ADHD children tend to have difficulty with academic performance and scholastic achievement. It is assumed that this poor academic performance is a result of inattention and impulsiveness in the classroom. When ADHD children are given medication to control their inattention and impulsiveness, their academic productivity has been shown to improve.

ADHD children have also been shown to have a high number of associated emotional and behavioral difficulties. As mentioned before, ADHD boys tend to show higher levels of aggressive and antisocial behavior than ADHD girls and normal children. Additionally, it is estimated that up to 50 percent of ADHD children have at least one other disorder, and the DSM-5 now allows ADHD to be included in a comorbid diagnosis with autism spectrum disorder. Many of these problems are related to depression
and anxiety. Many ADHD children also have severe problems with temper tantrums, stubbornness, and defiant behavior. It is also estimated that up to 50 percent of ADHD children have impaired social relations; that is, they do not get along with other children. In general, there are many problems associated with ADHD, and this may be part of the reason that researchers have been so intrigued by this disorder.

Researchers must understand a disorder before they can attempt to treat it. There are a variety of theories on the etiology of ADHD, but most researchers have come to believe that there are multiple factors that influence its development. It appears that many children may have a biological predisposition toward ADHD; in other words, they may have a greater likelihood of developing ADHD as a result of genetic factors. This predisposition is exacerbated by a variety of factors, such as complications during pregnancy, neurological disease, exposure to toxins, family adversity, and inconsistent parental discipline. Although a very popular belief is that food additives or sugar can cause ADHD, there has been almost no scientific support for these claims. Because so many factors have been found to be associated with the development of ADHD, it is not surprising that numerous treatments have been developed for the amelioration of ADHD symptoms. Although numerous treatment methods have been developed and studied, ADHD remains a difficult disorder to treat effectively.

Drug Therapies

Treatments of ADHD can be broken down into roughly two categories: medication and behavior or cognitive behavior therapy with the individual ADHD child, parents, or teachers. It should be noted that traditional psychotherapy and play therapy have not been found to be effective in the treatment of ADHD. Stimulant medications have been used in the treatment of ADHD since 1937. The most commonly prescribed stimulant medications are methylphenidate (Ritalin and Concerta), pemoline (Cylert), and dextroamphetamine (Dexedrine). As of 2014, the Federal Drug Administration (FDA) had approved three nonstimulant medications to treat ADHD. Strattera was the first nonstimulant drug approved and is prescribed to both children and adults. Intuniv and Kapvay are approved for children ages six through seventeen. Behavioral improvements caused by medications include better impulse control and improved attending behavior. Overall, approximately 75 percent of ADHD children on stimulant and nonstimulant medication show behavioral improvement, and 25 percent show either no improvement or decreased behavioral functioning. The findings related to academic performance are mixed. It appears that these medications can help the ADHD child with school productivity and accuracy but not with overall academic achievement. In addition, although ADHD children tend to show improvement while they are on a stimulant or a nonstimulant medication, there are rarely any long-term benefits to their use and can, in general, can be seen as only a short-term management tool.

Antidepressant
medications such as imipramine and fluoxetine (Prozac) have also been used with ADHD children. These medications are sometimes used when stimulant medication is not appropriate (for example, if the child has motor or vocal tics). Antidepressant medications, however, like stimulant and nonstimulant medications, appear to provide only short-term improvement in ADHD symptoms. Overall, the use or nonuse of medications in the treatment of ADHD should be carefully evaluated by a qualified physician (such as a psychiatrist). If the child is started on medication for ADHD, the safety and appropriateness of the medication must be monitored continually throughout its use.

Behavior Therapies

Behavioral and cognitive behavior therapy has been used with ADHD children, their parents, and their teachers. Most of these techniques attempt to provide the child with a consistent environment in which on-task behavior is rewarded (for example, the teacher praises the child for raising his or her hand and not shouting out an answer) and in which off-task behavior is either ignored or punished (for example, the parent has the child sit alone in a chair near an empty wall, a “time-out chair,” after the child impulsively throws a book across the room). In addition, cognitive behavior therapies try to teach ADHD children to internalize their own self-control by learning to “stop and think” before they act.

One example of a cognitive behavior therapy, which was developed by Philip Kendall and Lauren Braswell, is intended to teach the child to learn five “steps” that can be applied to academic tasks as well as social interactions. The five problem-solving steps that children are to repeat to themselves each time they encounter a new situation are the following: Ask “What am I supposed to do?” and then ask, “What are my choices?” Concentrate and focus in; make a choice and ask, “How did I do?” (If I did well, I can congratulate myself, and if I did poorly, I can try to go more slowly the next time.) In each therapy session, the child is given twenty plastic chips at the beginning of the session. The child loses a chip each time he or she does not use one of the steps, goes too fast, or gives an incorrect answer. At the end of the session, the child can use the chips to purchase a small prize; chips can also be stored in a “bank” to purchase an even larger prize in the following sessions. This treatment approach combines the use of cognitive strategies (the child learns self-instructional steps) and behavioral techniques (the child loses a desired object, a chip, for impulsive behavior).

Overall, behavioral and cognitive behavior therapies have been found to be relatively effective in the settings in which they are used and at the time they are being instituted. Like the effects of medication, however, the effects of behavioral and cognitive behavior therapies tend not to be long lasting. There is some evidence to suggest that the combination of medication and behavior therapy can increase the effectiveness of treatment. In the long run, however, no treatment of ADHD has been found to be truly effective, and in a majority of cases, the disorder persists into adulthood.

History and Changing Diagnostic Criteria

Children who might be diagnosed as having ADHD have been written about and discussed in scientific publications since the mid-1800s. A focus on ADHD began in the United States after an encephalitis epidemic in 1917. Because the damage to the central nervous system caused by the disease led to poor attention, impulsivity, and overactivity in children who survived, researchers began to look for signs of brain injury in other children who had similar behavioral profiles. By the 1950s, researchers began to refer to this disorder as “minimal brain damage,” which was then changed to “minimal brain dysfunction” (MBD). By the 1960s, however, the use of the term MBD was severely criticized because of its overinclusiveness and nonspecificity. Researchers began to use terms that more specifically characterized children’s problems, such as “hyperkinesis” and “hyperactivity.”

The Diagnostic and Statistical Manual of Mental Disorders (DSM), first published by the American Psychiatric Association in 1952, is the primary diagnostic manual used in the United States. In 1968, the second edition, called DSM-II, presented the diagnosis of “hyperkinetic reaction of childhood” to characterize children who were overactive and restless. By 1980, when the third edition (DSM-III) was published, researchers had begun to focus on the deficits of attention in these children, so two diagnostic categories were established: “attention-deficit disorder with hyperactivity (ADD with H)” and “attention-deficit disorder without hyperactivity (ADD without H).” After the publication of DSM-III, many researchers argued that there were no empirical data to support the existence of the ADD without H diagnosis. In other words, it was difficult to find any children who were inattentive and impulsive but who were not hyperactive. For this reason, in 1987, when the revised DSM-III-R was published, the only diagnostic category for these children was “attention-deficit hyperactivity disorder (ADHD).”

With the publication of the fourth version of the manual, the DSM-IV, in 1994, three distinct diagnostic categories for ADHD were identified: ADHD predominantly hyperactive-impulsive type, ADHD predominantly inattentive type, and ADHD combined type. The type of ADHD diagnosed depends on the number and types of behavioral symptoms a child exhibits. Six of nine symptoms from the hyperactivity-impulsivity list but fewer than six symptoms from the inattention list lead to a diagnosis of ADHD predominantly hyperactive-impulsive type. Six of nine symptoms the inattention list but fewer than six symptoms from the hyperactivity-impulsivity list lead to a diagnosis of ADHD predominantly inattentive type. A child who exhibits six of nine behavioral symptoms simultaneously from both lists receives a diagnosis of ADHD combined type.

The eighteen criteria used in the DSM-IV to diagnose ADHD were carried over to the DSM-5, which was published and released in 2013. The wording criterion for onset of ADHD has been changed, however, from "some" of the inattentive or hyperactive "symptoms that caused impairment were present before age seven years" in the DSM-IV to "several" inattentive or hyperactive "symptoms were present prior to age twelve" in the DSM-5. The DSM-5 also added a reduced symptom threshold for adults with a minimum of five symptoms (as opposed to the six required for children) for both the inattention and the hyperactivity/impulsivity aspects of the disorder.

Although the diagnostic definition and specific terminology of ADHD will undoubtedly continue to change throughout the years, the interest in and commitment to this disorder will most likely persist. Children and adults with ADHD, as well as the people around them, have difficult lives to lead. The research community is committed to finding better explanations of the etiology and treatment of this common disorder.

Bibliography

Alexander-Roberts, Colleen. The ADHD Parenting Handbook: Practical Advice for Parents from Parents. Dallas: Taylor Trade, 1994. Print.

Barkley, Russell A. Attention-Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment. 3d ed. New York: Guilford Press, 2005. Print.

Goldstein, Sam, and Joy Jansen. “The Neuropsychology of ADHD.” In The Neuropsychology Handbook, edited by Arthur MacNeill Horton, Jr., and Danny Wedding. 3d ed. New York: Springer, 2007.Print.

Hallowell, Edward M., and John J. Ratey. Driven to Distraction: Recognizing and Coping with Attention Deficit Disorder. New York: Random House, 2011. Print.

Kendall, Philip C., and Lauren Braswell. Cognitive-Behavioral Therapy for Impulsive Children. 2d ed. New York: Guilford Press, 1993.Print.

Parker, Charles E. New ADHD Medication Rules: Brain Science and Common Sense. 2nd ed. New York: Köehler Books, 2013. Print.

Ramsay, Russell J. Cognitive-Behavioral Therapy for Adult ADHD: An Integrative Psychosocial and Medical Approach. 2nd ed. New York: Routledge, 2015. Print.

Wender, Paul H. ADHD: Attention-Deficit Hyperactivity Disorder in Children and Adults. New York: Oxford University Press, 2000. Print.