What is pathology? |

Science and Profession

The science of pathology seeks to identify accurately the etiology of a disease and its development in the human body, which in turn leads to other studies focused on the diagnosis, treatment, and prevention of the disease.

A pathologist may be a medical doctor or hold a doctoral degree in a related field such as cell biology or microbiology. He or she may be employed in one of several different types of work, such as research, clinical, surgical, and forensic pathology. The human body is a complex structure and, as in all living organisms, its basic unit of function is the cell. Similar cells are organized into tissues, tissues form organs, and organs are grouped into systems. All systems in the body must work together to maintain homeostasis. If this internal stability is changed too drastically, a disease results. To understand a disease thoroughly—and ultimately to diagnose, prevent, or treat it—its pathogenesis must be understood. This term includes the cause of the disease, its method of damaging the body, and the changes resulting from its presence. A specific disease may have many causes, and its symptoms and severity may vary in different patients. Nevertheless, it is convenient to place a disease into one of seven groups based on its primary cause or manifestation in the body: genetic defects, infections, immune disorders, nutritional disorders, traumas, toxins, and cancers.

Genetic disorders are those caused by a defect in one or more genes. Genes, which are found on chromosomes, are duplicated and passed from one generation to another. Each gene is responsible for directing the manufacture of a protein. Every protein has a characteristic three-dimensional structure, on which its function depends. If a mutation occurs in a gene, the protein may function poorly or not at all. Although the pathogenesis of a genetic disease may involve devastating effects in the body, its origin may be traced to the function of a single protein. A person with hemophilia may bleed to death because of a lack of the gene for blood-clotting protein. In sickle cell disease, hemoglobin molecules are abnormal, which results in abnormal red blood cells and difficulty in transporting oxygen throughout the body. Changes in gene function occur throughout a person’s life. Many degenerative changes associated with aging are believed to be caused by aging genes and the subsequent loss of cell, tissue, and organ function.

Infections are those diseases that are caused by other organisms, usually microorganisms such as viruses, bacteria, protozoa, or fungi. Such organisms, called pathogens, are parasitic on body tissues or fluids. The damage from pathogens may be direct, resulting from tissue destruction, or may be caused by the toxins that they produce. Entamoeba histolytica, for example, is a protozoan that is ingested in contaminated water or food. It begins feeding on the tissues of the intestine and may cause ulcerlike lesions in the intestinal wall. Clostridium botulinum is the bacterial species that causes botulism. Its deadly effects are attributable not to tissue destruction but to its production of a poison that attacks the nervous system.

Immune disorders include immune deficiencies, autoimmune diseases, and allergies. The body’s immunity involves a complex system of checks and balances to protect against invasion by foreign cells or substances. It is the main defense against infectious diseases. When a person’s immune system is not functioning properly, the body is unable to fight off infections. Some individuals are born with immune deficiencies. Others may acquire the deficiency later in life through the use of immunosuppressive drugs to prevent rejection of an organ transplant or because of an infectious disease such as acquired immunodeficiency syndrome (AIDS). Regardless of the primary cause of the immune deficiency, the patient may die as a result of an infection that would be considered harmless in the general population. Another group of immune disorders includes the autoimmune diseases. In these disorders, the immune system begins to make antibodies against the body’s own tissues. For example, joint tissue is destroyed in rheumatoid arthritis, and nerve tissue is destroyed in multiple sclerosis. Allergies represent a third group of immune disorders. An allergic response is an overreaction to a substance that would ordinarily be considered harmless by the body. During this reaction, a chemical called histamine is released that causes such changes as rashes and upper respiratory symptoms. In more severe reactions, asthma or circulatory system collapse may occur.

Nutritional disorders include dietary deficiencies, excesses, and imbalances. Vitamins and minerals are needed to take part in certain chemical reactions in the body. In vitamin deficiencies, these reactions are blocked. For example, vitamin A is needed for the proper functioning of the nerve endings in the eye that are responsible for seeing black and white and in dim light; thus, a person with a vitamin A deficiency may develop night blindness. Proteins, carbohydrates, and fats must be ingested in sufficient amounts to supply energy and raw materials to build body tissue. Excessive consumption, however, is associated with such conditions as obesity, diabetes, and heart disease.

Trauma generally refers to injury done to the body by an external force, such as in an automobile accident. The damage to the body may be relatively minor but still have serious effects. Damage to a blood vessel may cause hemorrhaging and subsequent loss of blood. Injury to the brain or spinal cord may result in paralysis or loss of other body function. Physicians also use the word “trauma” to mean any occurrence that damages the body or organs. High fever, for example, may be said to cause trauma to the brain. Extreme emotions may also have effects on the body.

Toxins are poisons that may originate from the surroundings of an individual and be absorbed through the skin or inhaled. A person can be overcome by carbon monoxide from a defective furnace or automobile heater, for example. Toxins may also be ingested in water or food. Drug overdoses or accidental ingestion of household chemicals will also cause toxic reactions. Medical ecology is a field of medicine that concerns itself with the long-term toxic effects of chemicals released into the environment from plastics or other materials associated with modern life.

Cancers arise when the cell division process becomes abnormal. Ordinarily, cells in the body divide at a limited rate that is characteristic of a particular tissue. When cells divide rapidly in an uncontrolled manner and metastasize (spread) to other parts of the body, the condition is termed a malignancy or cancer. Cancers are grouped according to the type of tissue from which they develop. Carcinomas arise from epithelial tissue such as skin. Sarcomas arise from connective tissue such as bone or muscle. Leukemias result from abnormal and rapid reproduction of white blood cells in the bone marrow. Lymphomas are cancers of the lymphatic tissues, such as the lymph nodes or spleen. The severity of the cancer and the chances for recovery depend on the extent of the cancer when first diagnosed, the type of tissue or location involved, the speed at which the cells are dividing, and whether the cancer has spread to other areas of the body.

While it is convenient to place pathologies into separate groups, in reality their causes and effects overlap. An individual who is malnourished may have a weakened immune system and be vulnerable to infectious diseases. The immune system attacks not only foreign cells from outside the body but also abnormal cells arising within the body, such as cancer. Thus, patients with AIDS often develop cancer. Some individuals are at increased risk for cancer because of genetic factors called oncogenes. If these individuals smoke or eat unwisely, they may develop cancer, while others with the same inherited risk who adopt a prudent lifestyle do not. It is important for researchers and physicians to understand these complex pathological relationships so that they can diagnose and treat such conditions.

Diagnostic and Treatment Techniques

A pathologist must be familiar with the typical test values associated with body functions and with the microscopic appearance of healthy cells and tissues in order to be able to differentiate correctly a normal condition from a pathological one. This body of knowledge has involved the collection of tissues and the measurement of values gleaned from years of medical treatment and research. Although based on large populations, these values may be misleading. For example, the amounts of blood cholesterol were measured in Americans, and the average level of cholesterol was labeled “normal.” In reality, this value has been shown to be unhealthy and linked to heart disease.

Research pathology concentrates on the basic study of diseases or disorders. This type of study usually focuses on the cellular and biochemical aspects of a disease. Information is exchanged with other researchers in an effort to gain a complete understanding of the etiology of a disease and the mechanisms by which it damages the body. Laboratory experiments may be performed to determine if the condition can be stopped or at least slowed.

Other pathologists are more closely associated with patient treatment. A clinical pathologist is involved in the diagnosis of disease through study of body fluids, secretions, and excretions. Such a person must be knowledgeable in hematology (the study of blood), microbiology, and chemistry. A surgical pathologist is responsible for testing samples of cells and tissues excised during surgery. In such a procedure, called a biopsy, a small section of tissue is taken from the affected area and sent to the laboratory. The pathologist then examines the sample using a microscope and determines whether the tissue is normal or whether it indicates the presence of cancer or some other disease state.

At one time, it was necessary to perform what was known as exploratory surgery if laboratory tests and x-rays did not lead to a diagnosis. Less invasive, and safer, techniques have been developed to eliminate that need. Fiber-optic methods involve the use of light shining through a flexible tube containing glass fibers. The flexible tube can be inserted through a body opening or through a small incision, allowing the physician to see internal cavities and determine if any visible abnormalities are present or to perform a biopsy. In some cases, the condition can be corrected without further surgery.

Many other tools and techniques are available to clinical and surgical pathologists. Some abnormalities can be observed directly, such as a rash or external tumor. Microscopes are used to detect changes that are too minute to be seen by the naked eye. Another tool used to diagnose disease or disorders is the medical x-ray, which can determine the presence of a broken bone, kidney stones, or dense tumors. Soft tissues are not so easily visualized using normal x-ray techniques. Ingestion of an opaque substance such as barium may help to delineate the outline of a structure such as the esophagus or intestine. Other medical imaging procedures, such as ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) scans, allow even more detailed visualization of body structures.

An autopsy pathologist examines the body after death. In a hospital setting, the purpose of an autopsy is usually to confirm or determine the natural cause of death. Even when the cause is known, an autopsy may be requested, since information obtained in this way may lead to better understanding of the pathological processes that resulted in death and suggest possible ways of preventing deaths in the future.

A forensic pathologist, also called a coroner or medical examiner, is an autopsy pathologist who works closely with the police and criminal justice officials. This relationship is especially important if there are suspicious circumstances surrounding the death or the discovery of the body, in order to determine whether the death has resulted from an intentional poisoning or a violent act. In some cases, a coroner must also attempt to identify the body. Such abnormalities in the body as scars, healed fractures, and dental cavities can aid in this effort. Samples of cells may be used for DNA fingerprinting, a comparison of genetic material from the deceased to that of someone believed to be a close relative, in an attempt to verify identification. If it is determined that a murder has occurred, the pathologist contributes to the investigation by determining such facts as the cause and time of death. Special care must be taken during any autopsy since the information may be used as legal evidence.

The correct diagnosis and identification of the etiology of a disease are essential to providing insight into possible treatments. Pathologists also play a key role in determining the mode of transmission. The following historical examples illustrate this application of pathology.

In the 1930s, it was discovered that the urine of some developmentally disabled children had a peculiar odor. Analysis of the urine showed the presence of an abnormal chemical that damaged the nervous system, resulting in mental deficiencies. The chemical was found to result from a failure of the body to make an enzyme necessary to break down the amino acid phenylalanine, which in turn was the result of a genetic defect, termed phenylketonuria (PKU). Simple blood and urine tests can determine the presence of this defect at birth. While this disease cannot be cured, those with PKU can be placed on a special diet low in phenylalanine, and so avoid the buildup of the amino acid and its resulting damage. In this genetic disease and others, once the precise mechanism of damage is found, efforts can be made to identify the presence of the gene and then to lessen its effects.

In July 1976, more than five thousand members of the American Legion attended a convention in Philadelphia, Pennsylvania. Within two weeks of returning home, nearly two hundred of them became ill, and twenty-nine of these died. Laboratory tests and autopsies identified the process that caused death as severe pneumonia accompanied by high fever but could not determine its origin. Although a pathogen was suspected, none could be found through microscopic examination of tissues or culture studies. Attention turned to the hotel and its air conditioning system in an attempt to determine if some toxin had spread through the air ducts, but no such substance was found. Several months later, a pathologist at the Centers for Disease Control in Atlanta, Georgia, was examining lung tissue sections taken from chick embryos and discovered the bacteria that had caused the illness, now known as Legionnaires' disease. Further tests showed them to be sensitive to the antibiotic erythromycin. When subsequent cases occurred, prompt diagnosis of the disease allowed the correct treatment to be given. The presence of these bacteria in water tanks associated with large air conditioning systems has led to preventive measures.

In 1981, the first cases of AIDS were identified. While the mode of transmission was discovered fairly quickly, it was not until 1986 that the human immunodeficiency virus (HIV) was identified. The pathogenesis of this disease begins with the infection of white blood cells, called helper T cells, that are an essential link between the identification of an invading pathogen and the production of antibodies by other cells called B cells. At first, the body begins to make antibodies against the virus as it would any other infectious disease. Then, over a period of several years, an increasing number of T cells are infected and destroyed. Eventually, the body loses the ability to make the antibodies necessary to fight all infectious diseases and to destroy cancer cells. After further study of the virus, researchers were able to discover a chemical, azidothymidine, or AZT (later called zidovudine), that could interfere with a key enzyme needed by the virus to reproduce. Although it could not cure the disease, the drug slowed its effects. AIDS research efforts are not aimed solely at attempts to kill the virus: by studying its pathogenesis, the means may be found to counteract the effects of the disease on the body’s immune system.

Perspective and Prospects

In the early days of medicine, knowledge of pathology was limited to what could be observed directly through the human senses. Treatments were empirical, a matter of trying different drugs or procedures until one was found that worked. Most basic knowledge of human anatomy and physiology was lacking. Often, human autopsies were not permitted because of religious and cultural practices.

A culture’s beliefs about disease influence medical practice. From the time of the ancient Greeks until the rise of modern medicine, various theories were accepted. Some believed that disease had supernatural origins. The term influenza, for example, came from the belief that the disease was caused by the influence of the stars. Others believed that the body’s functions were dependent on fluids in the body, called humors. Bleeding was used to release the bad humors that were causing the disease.

By the seventeenth century, dissection of cadavers was practiced to identify completely the normal and abnormal gross anatomy of the human body. The microscope was developed and used to study human tissues. In the late nineteenth century, it was shown that microorganisms could cause disease, which in turn led to specific tactics aimed at prevention and treatment. With knowledge of the infectious process and the development of anesthesia, surgery became more widespread. This trend, in turn, increased the knowledge of disease processes in tissues and organs.

In the twentieth century, more sophisticated techniques were developed to focus on processes at the cellular level. The electron microscope allowed researchers to visualize structures within cells. Other research showed that series of chemical reactions, called metabolic pathways, are necessary for proper cell function. The comparison of these pathways in normal cells with those in abnormal cells enabled researchers to understand the pathogenic effect of toxins and many genetic diseases. The use of computers in medical analysis has increased the precision of laboratory tests and has permitted the detection of abnormal chemicals in smaller amounts than were possible before.

During the effort to map the human genome—that is, to identify and locate all the genes found on the forty-six human chromosomes—one of the techniques employed was to compare the chromosomes of individuals known to have genetic diseases with those who do not, and so identify the abnormal gene. Identification of oncogenes (cancer-causing genes) or genes linked to such diseases as diabetes mellitus and heart disease may alert individuals at high risk in time for them to get regular diagnostic tests or to change their lifestyles. Knowledge gained by taking the study of disease to the genetic level will ultimately lead to more effective treatments and prevention for these and other pathological conditions.

Bibliography

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Corrigan, Gilbert. Essential Forensic Pathology: Core Studies and Exercises. Boca Raton: CRC, 2012. Print.

Crowley, Leonard V. Introduction to Human Disease: Pathology and Pathophysiology Correlations. Boca Raton: CRC, 2012. Print.

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What is chronobiology? |

Science and Profession

Chronobiology refers to the study of various cycles or rhythms that are fundamental to living organisms, including human beings. Many of the early observations were made on plants and nonhuman animals, but the basic concepts also apply to human biology and medicine. In the twentieth century, early findings about cyclical changes in symptoms, body weight, pulse rate, and body temperature were substantiated and broadly expanded to include numerous aspects of human biology and medicine. Well-informed physicians now expect rhythms in their patients’ behavior, physiology, and response to therapy. The extensive research on biological rhythms in diverse organisms makes up the specialized field called chronobiology. The presence of circadian, menstrual, weekly, seasonal, and other rhythms in humans necessitates a consideration of these cycles in any comprehensive approach to medical practice.

Despite their importance, the exact nature of these rhythms has not been resolved. Living organisms behave as though they have internal oscillators or biological clocks that time their activities. Some research provides evidence that many of the body’s cells each have such internal timers. Until the exact causes for the various biological rhythms have been identified, there will be some limitations to the benefits derived from knowledge of their characteristics. An unsettled dispute concerns whether the actual timing information for circadian and other rhythms comes from within the organism (endogenous) or from the environment (exogenous). It is expected that travel to space beyond the moon may ultimately answer this question. Astronauts may have sufficient internal timing information to survive, or it may be necessary to create a rhythmic environment of change in light-dark cycles and perhaps magnetic field variations to provide vital timing information. In the meantime, there is much that is known in chronobiology.

In mammals, an important circadian timing mechanism resides in a cluster of cells called the suprachiasmatic nuclei, or SCN, which are located in the hypothalamus of the forebrain. From studies on laboratory mammals, it has been learned that removal of the SCN abolishes many of the body’s circadian rhythms. In humans, chance tumors in this area are often found to disrupt the circadian rhythms of the patient. In laboratory mammals, it has been shown that there is a separate pathway from the eyes to the SCN that allows information about changes in the light-dark schedule to reach this part of the brain. Therefore, there is intense interest in learning more about the SCN and how they regulate circadian rhythms.

Additionally, the pineal gland, a small gland attached to the epithalamus of the forebrain, receives information from the SCN about the light-dark schedule. A hormone produced by the pineal gland called melatonin is released into the bloodstream at night and suppressed during daylight. Melatonin plays a significant role in the timing of body rhythms and sleep cycles. When melatonin levels rise, the brain interprets this as bedtime, a factor that has led to its increasing use as a treatment for jet lag.

The general physiology of the other tissues of the body is organized according to rhythmic processes. The exact question of whether such rhythms are dependent on the SCN is still a point of controversy. Nevertheless, the greater application of chronobiology to medicine does not have to await the solution of such theoretical questions. Even now, a wide variety of examples can be cited of the utility of chronobiologic principles in medicine.

Diagnostic and Treatment Techniques

Four medical applications of chronobiology will be discussed. One area from psychiatry is the treatment of seasonal affective disorder. Three from other areas of medicine are the chronobiological treatment of asthma, cancer, and jet lag.

Seasonal affective disorder, or SAD, is characterized by depression beginning each year as daylight shortens and fully remitting when days start to lengthen, sometimes switching to mania. The condition is related to where people live and the corresponding hours of sunlight; the condition remits in a few days when sufferers travel to sunnier climes and worsens as they travel to areas where the days are shorter. As many as one in four persons in the northern latitudes may suffer from SAD, and female sufferers outnumber male ones. Although the disorder has been recognized only recently, for years writers and poets have noted seasonal depression in themselves and others.

Some patients take a midwinter vacation to a sunny climate to alleviate the condition. For those who cannot travel, the use of artificial lights has been introduced. Glow lights are placed in the homes of SAD patients and used early in the morning as well as after sunset to lengthen daylight hours. Morning lights appear to bring particularly prompt relief. Relapses have been reported when light is withdrawn. Research is currently under way to determine when during the day light is most effective, how much light is needed, and the mechanisms by which light works to fight SAD.

Some details are emerging about this process. The human forebrain contains a small organ about the size of a pea that produces the hormone melatonin according to a circadian schedule. Melatonin is usually released into the bloodstream during the night. The use of bright light therapy seems to inhibit the release of melatonin and thereby to cause other changes in the brain chemistry. In some mammals, this mechanism may be important in regulating their seasonal behavior. In humans, the situation is more complex, and an adequate theory for the neurochemical basis of SAD and other mental disorders has yet to be advanced.

Asthma sufferers have long known that their symptoms worsen at night. This increase in coughing, wheezing, and breathlessness at night has been identified only recently with circadian rhythms rather than environmental factors. At first, some researchers thought that asthma was worse at night because the patients were lying down. It has been shown, however, that the symptoms show their circadian periodicity whether the person is lying down or not. The normal nightly decrease in airway passage diameter in the lungs of normal persons is exaggerated in the asthmatic. The most dangerous hours for the asthmatic are the very early morning hours, a time when there are more deaths among asthmatics. Interestingly, asthmatics who become adapted to a nighttime work schedule shift their most severe asthma symptoms to the daytime sleep period.

Experts in the field such as Michael H. Smolensky of the University of Texas contend that much more research needs to be done on the role of circadian rhythms in asthma and its treatment. For example, adrenocortical hormones, which are powerful anti-inflammatory agents, have been used successfully to treat asthmatics. It was discovered that the time of day when the hormones were given was of great importance. If the hormones are given in the evening, the patient’s own adrenal gland is inhibited. Therefore, the best time to give such hormones is in the early morning, near the time when they are normally released in the body.

Theophylline is a drug that has been very successful in ameliorating the symptoms of asthmatics. It has been found that certain types of sustained-release theophylline are effective in reducing the early morning symptoms if the drug is taken the night before. In the study of asthma, the benefit of considering chronobiology has become obvious, and any new products to treat asthma need to be evaluated chronobiologically before they are made available to the general public.

Cancer diagnosis and treatment are aspects of medicine that are receiving increased consideration by chronobiologists. The normal growth of tissues occurs by cell division, or mitosis, a rhythmic process that is normally precisely regulated. Cancer is essentially unregulated mitosis, resulting in the growth of a tumor that is no longer subject to the control mechanisms of the body. Yet even this breakdown in regulation has its seasons. In human males, some types of testicular cancer are more often diagnosed in the winter, and in females some types of cervical cancer have a peak occurrence in the summer.

The treatment of cancer involves the use of surgery, radiation therapy, or chemotherapy in an attempt to remove or kill the cancerous cells without substantial damage to the normal tissues. Early studies in animal models demonstrated that there are often specific times of the day that these types of cancer treatment can be most effective. In a few cases, the tumor may have a rhythm of mitosis that is no longer synchronized to the rhythm of the surrounding tissue. In these cases, it may be possible to administer drugs or radiation that inhibits mitosis according to a schedule that will affect the cancer cells but will not harm the host tissue. More often, there will be a mixed effect of the timed treatment, so that some suppression of mitosis occurs along with some side effects.

The application of chronobiology to the treatment of breast cancer has raised hopes that there can be a marked improvement for survival rates of women who undergo breast surgery. William J. M. Hrushesky of Albany Medical College found that women who had breast surgery near the time of menses had a higher risk of recurrence and death than those patients who had surgery near the middle of the menstrual cycle. It has also been observed that the diagnosis of breast cancer in the United States has a two-peaked seasonal rhythm in the spring and the fall. There is also evidence that the body temperature of the breast in normal women has a circadian rhythm along with perhaps an additional seven-day periodicity, whereas breasts with tumors have abnormal temperature rhythms of about twenty hours. This information may help in the early diagnosis of breast cancer if suitable automatic monitoring devices are used to measure breast temperature.

Jet lag may appear to be more of an inconvenience than a serious medical problem until one considers the disastrous consequences of a plane crash caused by pilot error or a poorly made decision by a diplomat in an international crisis. Wiley Post and Harold Gatty, on their 1931 plane trip around the world, were the first persons to suffer from this disorder. Essentially, the body is subjected to a shift in the day-night schedule, with sleep and meal times shifted earlier or later depending on the number of time zones crossed and the direction of the flight. The symptoms are general malaise, headaches, fatigue, disruptions of the sleep-wake cycle, and gastrointestinal disorders. There are individual differences in the time required to overcome jet lag. In general, younger and healthier people are better able to cope with such change.

A shift of six hours, such as a flight between New York and Paris, requires a substantial reorganization of one’s circadian rhythms. It can take from two days to two weeks to resynchronize. Adaptation is slowest when one stays indoors and continues on a “home-time” schedule. Eastward flights are less easily tolerated than westward flights; the delays in resynchronization can take almost twice as long. The reason for the difference is that when one flies east, the sun comes up earlier relative to “home time.” It is easier for most people to “advance” than to shift “backward”—that is, to go from day to night than to go backward from night to day. For this reason, it is suggested that travelers fly early in the day when flying east and later in the day when flying west.

Unfortunately, little consideration has been given to chronobiology in scheduling work time and time off. Pilots, diplomats, businesspersons, and other time zone travelers often perform poorly when their body rhythms are disturbed by jet lag. Similarly, people who must change their work shift every few weeks often find their performance levels dropping.

It should be realized that the living body has myriad hormones, enzymes, and other important constituents that have rhythms of several different periods. Maintaining the correct time relationship between the rhythms can be critical for normal health. In the diagnosis of disease, chronobiology has to be taken into account. Erhard Haus of the St. Paul-Ramsey Medical Center has spent many years detailing the circadian and other rhythms that must be considered. What is normal for the morning hours may be pathological for the evening hours. These rhythmic values are yet to be determined for many important diagnostic measurements.

In 2005, a research study by the Feinberg School of Medicine and Northwestern University confirmed previous findings that school start times for adolescents are too early. In adolescents, melatonin, the hormone that helps induce sleep, increases later in the evening, causing melatonin levels to stay at high levels until approximately 8:00 a.m. There is no known way to change melatonin levels; for example, going to bed earlier does not cause melatonin to decrease earlier. The researchers encouraged parents and school districts to start later, as research consistently shows that adolescents have their poorest academic performance in the morning and have consistently better cognitive functioning later in the day. The researchers noted that school start times are easily modified. Many previous studies have shown the same effect, and some school districts have instituted later start times, with many schools reporting improved cognitive functioning and mood among students.

Perspective and Prospects

One of the earliest written observations of a biological cycle was by Androsthenes, a soldier marching with Alexander the Great in the fourth century BCE, who recorded that the tamarind tree opens its leaves during the day and closes them at night. In experiments on similar leaf movements in other plants, the astronomer Jean Jacques d’Ortous de Mairan in 1729 found that plants held in the dark continued to open and close their leaves on a roughly twenty-four-hour schedule. Thus, circadian rhythms in plants were shown not to be simple responses to the rising and setting of the sun but rather internal oscillations.

Early observers more interested in humans also identified rhythms. In the fifth century BCE, Hippocrates reported that his patients had twenty-four-hour fluctuations as well as longer-term rhythms in their symptoms. Herophilus of Alexandria in the third century BCE observed a daily change in the human pulse rate. The Italian scientist Sanctorius in 1711 made repeated measurements of his own body weight and the turbidity of his urine, both of which he found to vary during the month. Later, he went to the extreme measure of constructing a giant scale and living on its huge pan so that a frequent record could be made of his changing weight. The French scientists Armand Seguin and Antoine-Laurent Lavoisier in 1790 did research that revealed circadian rhythms in the body weight of men. These researchers suggested that men who did not show such circadian rhythms in body weight should be suspected of being ill. The British scientist John Davy in 1845 reported that he had found both circadian and seasonal rhythms in his own body temperature.

The historical citations of persons taking an interest in chronobiology in past centuries were of only passing concern and did not, in most cases, help to establish this field. Chronobiology as a discipline has received attention from the medical community only since about the 1970s, and many of its contributions to improving health are yet to be realized. The foremost student of chronobiology as applied to medicine has been Franz Halberg of the University of Minnesota. He has repeatedly called the attention of the medical community to the importance of biological rhythms in maintaining health and in the diagnosis and treatment of disease. Halberg has promoted the use of “autorhythmometry,” or the self-measurement of one’s physiological variables to monitor one’s changing health. It has been shown that this method can be used effectively even by groups of schoolchildren.

The phase or the timing of the peaks and troughs of circadian rhythms is germane in both diagnosis and treatment. The advent of portable automatic recording devices that store physiological data on computer chips is opening up a means of documenting a patient’s circadian rhythms around the clock for weeks at a time.

The diagnosis of diabetes mellitus has been shown to depend to an extent on the time of day that the various tests, such as the glucose tolerance test, are administered. Some diabetics are “matinal” diabetics and do not have trouble regulating their blood glucose levels until the afternoon. These persons need to have glucose tolerance tests administered in the afternoon in order to reveal their diabetes. Many additional examples of the importance of chronobiology in diagnosis and treatment exist. As more physicians and health professionals become familiar with the concepts and application of chronobiology, the effectiveness of health care will be enhanced.

Bibliography

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Columbus, Frank, ed. Frontiers in Chronobiology Research. New York: Nova Science, 2006.

Dunlap, Jay, Jennifer Loros, and Patricia Decourse, eds. Chronobiology: Biological Timekeeping. Sunderland, Mass.: Sinauer, 2003.

Endres, Klaus-Peter, and Wolfgang Schad. Moon Rhythms in Nature: How Lunar Cycles Affect Living Organisms. Translated by Christian von Arnim. Edinburgh, Scotland: Floris Books, 2002.

Garaulet, Marta, and Jose M. Ordovás, eds. Chronobiology and Obesity. New York: Springer, 2013.

Lee-Chiong, Teofilo L., ed. Sleep Medicine Essentials. Malden: Wiley-Blackwell, 2011.

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Sehgal, Amita. Molecular Biology of Circadian Rhythms. Hoboken, N.J.: Wiley-Liss, 2004.

Waterhouse, J. M., et al. Keeping in Time with Your Body Clock. New York: Oxford University Press, 2003.

In the poem "To Everything There Is a Season," are all activities the poet mentions permanent? Or do they come or go? How do you know?

The poem begins with the statement that everything has its season. This implies a seasonal rhythm like the seasons in nature. However, the first example given is "a time to be born and a time to die." One might immediately think of the birth and death of a person, or the birth and death of oneself, which only happens once in the given person's lifetime. That death is permanent.

All the other events in the...

The poem begins with the statement that everything has its season. This implies a seasonal rhythm like the seasons in nature. However, the first example given is "a time to be born and a time to die." One might immediately think of the birth and death of a person, or the birth and death of oneself, which only happens once in the given person's lifetime. That death is permanent.

All the other events in the poem speak to things that are cyclical or recurring. Planting and reaping happen each year in spring and fall. People know that laughing and weeping are cyclical: Although when one is extremely sad, it feels like one will never laugh again, even devastating sorrow recedes in its intensity, allowing the grief-stricken person to eventually laugh again. Breaking down and building up, keeping and throwing away, and ripping out seams and sewing them up again are all things that happen repeatedly in one's life. Loving and hating, keeping quiet and speaking, and winning and losing all happen over and over again for any given person.

Therefore, the only thing in the poem that seems of a permanent nature is death. From the context of the poem, one could infer that the poet wants to make the point that death, despite its seeming permanence, is in reality a part of a cycle that will lead to rebirth. This poem is rooted in the passage from the Old Testament book of Ecclesiastes, part of the Hebrew scriptures that is one of the Wisdom books. Keeping that religious worldview in mind, one might interpret the poem as presenting the concept of resurrection and an afterlife, seeking to prove it by showing that everything that is known is cyclical. Based on inductive reasoning where one makes a conclusion about what is not known based on what is known, death is not permanent but will come around to birth again. 

When did the process of using popularly elected, pledged delegates to elect presidential nominees begin?

The delegate based national convention can be traced back to 1832. Up until the 1824 election, known by Andrew Jackson's supporters as the "Corrupt Bargain," presidential nominees were selected directly by elected party leaders in congress. The 1824 election, however, witnessed the rise of the populist Jackson, who won the popular vote, but lost the electoral college when Henry Clay decided to throw his electoral votes to John Quincy Adams in return for the Vice Presidency. After that election, Jackson toured the country, becoming the first presidential candidate to appeal directly to "regular American voters," instead of party bosses. By 1832, the major political parties no longer selected presidential nominees through congressional votes, but instead held national conventions, which were still dominated by party bosses, who selected delegates to carry out their will and choose nominees.

This top-down, party-boss centered selection of delegates kept the nominating process firmly in the hands of senators, congressman, governors, state legislatures and industry titans, who had immense sway over the selection of presidential nominees. So while the delegate system dominated the presidential nominating process by the mid-1800s, these were not pledged delegates, or delegates chosen by popular vote.

In fact, it was not until 1910 that Oregon became the first state to hold presidential primaries, in order to give the general electorate a voice in the nominating contests. Yet even by 1920, when twenty states had adopted the presidential primary system, the delegates chosen at the national conventions were still not "bound" by the will of the people of their state, who voted in primaries. The delegates to the national conventions remained free to vote their conscience, or just as often, to vote the way their party's bosses wanted.

This tension played out in the 1912 Republican National Convention when incumbent President William Howard Taft clinched the nomination despite the fact that former president, Teddy Roosevelt, had been the more popular candidate in the non-binding primaries. The selection of Taft led to a rupture in the Republican Party, and as a result, Roosevelt ran as an Independent. This split in the Republican ticket allowed the progressive Democrat, Woodrow Wilson, to become president.

Yet it was not until after the chaotic 1968 Democratic National Convention that the modern system of “pledged delegates” was born. The 1968 Democratic Convention erupted into a floor fight and riots on the streets of Chicago after supporters of the late RFK backed anti-Vietnam War candidate, Eugene McCarthy, only to have their party leaders chose the pro-war, vice president, Hubert Humphrey, as the party’s nominee, despite the fact that he had not won a single primary. Shortly thereafter, the Frasier-McGovern Commission, chaired by then senator and future Democratic presidential nominee, George McGovern, established the “binding delegate system” that exists today in recognizable form in both the Democratic and Republic parties. Under this system, party nominees are chosen (in large part) based on the outcomes of primary elections in individual states, making the selection of presidential nominees more democratic and representative of the country as a whole.

What is human papillomavirus (HPV)?

Causes and Symptoms

Papillomaviruses are deoxyribonucleic acid (DNA) viruses than infect the skin and mucous membranes. Human papillomaviruses belong to a group of papillomaviruses that consists of nearly 120 strains. Most strains are virtually harmless, causing nothing more than benign skin warts (papillomas), while others cause genital warts
(condyloma acuminate) and may cause cancer.

Sexual contact is the primary mechanism by which the virus is acquired. About thirty HPV strains are sexually transmitted and can infect the external genitalia, urethra, anus, rectum, and sometimes the mouth and throat. Some low-risk strains cause genital warts, while the ten more virulent, high-risk strains cause abnormal Papanicolaou (Pap) tests and can in some instances cause cancer
of the cervix, vagina, vulva, penis, scrotum, anus, and/or the mouth and pharynx. Almost all cases of cervical cancer are the result of persistent HPV infection.

HPV is one of the most common sexually transmitted diseases. It has been estimated that more than 50 percent of sexually active people and up to 75 percent of sexually active women will develop an HPV infection during their lifetimes. Although the active viral infection is usually cleared by the immune system within a few months, it often remains dormant and can later cause a reinfection. Babies of infected women may contract potentially life-threatening HPV infections during delivery.

Women are more susceptible to developing genital warts. Many infected people, however, do not have genital warts. Infected women who are asymptomatic are often diagnosed by an abnormal Pap testing. In 2003, the Food and Drug Administration (FDA) approved the use of testing for high-risk HPV DNA as a routine screening procedure. DNA testing is also used as a confirmatory test for HPV after an abnormal Pap test.

Frequent Pap tests are the best way to diagnose HPV infections in asymptomatic women. About 10 percent of HPV-infected women will develop precancerous changes in their cervix, and about 8 percent of these women will develop the early stages of cervical cancer. Since persistent HPV infection is a hallmark of developing cervical cancer and since the cancer usually develops slowly over five to ten years, early diagnosis and treatment can be effective in preventing cervical cancer.

Genital warts are highly contagious and are transmitted through skin-to-skin contact from sexual activity. Risk reduction for HPV infection can be achieved by reducing the frequency of sexual contact. Condom use may partially reduce the risk of HPV infection in women. Since condoms do not cover all infected areas, however, their use does not eliminate the risk of infection. Research has suggested that microbicides may prevent infection if they are applied before sexual activity.

Treatment and Therapy

Since there is no cure for an HPV infection, the primary treatments are for warts.
Some treatments involve the use of topical ointments, creams, resins, and gels such as imiquimod (Aldara), podophyllin and podofilox (Condylox), and 5-fluorouracil, as well as trichloroacetic acid. Alternatively, warts may be removed by electrocautery, cryosurgery, laser, or conventional surgery.

In 2006, the FDA approved Gardasil, developed by Merck, and in 2009 approved Cervarix, developed by GlaxoSmith Kline, for use as preventive vaccines for the most prevalent HPV strains that cause cervical cancer and genital warts. Gardasil is active against two low-risk HPV strains that are the leading cause of genital warts and, as is Cervarix, active against two high-risk strains that cause up to 70 percent of cervical cancers in the United States. In 2010, the FDA approved the use of Gardasil for the treatment of precancerous lesions in an effort to prevent anal cancer. Gardasil is recommended for women between the ages of nine and twenty-six, and Cervarix is recommended for women between the ages of ten and twenty-five. The Center for Disease Control recommends that all eleven- and twelve-year-old girls receive the HPV vaccine, and that girls and women between thirteen and twenty-six receive "catch up" vaccinations. From 2008 to 2010, the percentage of girls between the ages of thirteen and seventeen who were behind on their vaccinations dropped from 84 to 75 percent. Routine Pap testing is still recommended, because the vaccines do not protect against all strains of HPV.

Perspective and Prospects

HPV was first described as a cause of skin warts in 1907. The relationship between sexual activity and cervical cancer was noted when it was discovered that women who have or who have had multiple sexual partners have a greater risk of developing cervical cancer than do women who have had few or no sexual partners. It was not until the 1980s that HPV was linked to cervical cancer.

The mechanism by which HPV causes cancer has recently been determined. Two proteins encoded by HPV DNA attach to and inactivate cellular proteins that control cell division. With these cellular proteins inactivated, the cell multiplies uncontrollably. Current research is directed toward the development of a vaccine that would inactivate the viral proteins that bind to and inhibit the proteins controlling cell division.

Since sisters of women with cervical cancer have a higher risk of developing cervical cancer, it is thought that genetics may be involved in the progression of the disease.

Bibliography

Crum, Christopher P., and Gerard J. Nuovo. Genital Papillomaviruses and Related Neoplasms. New York: Raven Press, 1991.

Dizon Don S., and Michael L Krychman. Questions and Answers About Human Papilloma Virus (HPV). Sudbury, Mass.: Jones and Bartlett, 2011.

Eifel, Patricia J., and Charles Levenback, eds. Cancer of the Female Lower Genital Tract. Hamilton, Ont.: B. C. Becker, 2001.

Gross, Gerd, and Geo von Krogh, eds. Human Papillomavirus Infections in Dermatovenereology. Boca Raton, Fla.: CRC Press, 1997.

McCance, Dennis J., ed. Human Papilloma Viruses. New York: Elsevier Science, 2002.

Markowitz, Lauri E., et. al. “Quadrivalent Human Papillomavirus Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP).” Morbidity and Mortality Weekly Report (MMWR) 56 (March 23, 2007): 1–24.

Mindel, Adrian, ed. Genital Warts: Human Papillomavirus Infection. Boston: Arnold, 1995.

Radosevich, James A. HPV and Cancer. New York: Springer, 2012.

Sterling, Jane C., and Stephen K. Tyring, eds. Human Papillomaviruses: Clinical and Scientific Advances. New York: Arnold, 2001.

Wailoo, Keith. Three Shots at Prevention: The HPV Vaccine and the Politics of Medicine's Simple Solutions. Baltimore, Md.: Johns Hopkins University Press, 2010.

What is acute necrotizing ulcerative gingivitis?

Definition

Acute necrotizing ulcerative gingivitis (ANUG) is a serious infection of the
gums that causes ulcers, swelling, and dead tissues in the mouth. Although a painful condition, it can be healed with treatment.

Causes

Acute necrotizing ulcerative gingivitis is typically caused by excess bacteria
in the mouth. Too much bacteria can form in the mouth from smoking, stress, a lack
of dental care, a virus, and a poor diet.

Risk Factors

Risk factors for ANUG include lack of dental care and overall poor dental hygiene; a poor diet; vitamin deficiencies; infections in the throat, teeth, or mouth; a compromised immune system; smoking; stress; and age thirty-five years or younger.

Symptoms

Symptoms of ANUG include pain in the gums, gums that bleed easily, bad taste in
the mouth, extremely bad breath, red and swollen gums, gray residue on the gums,
large ulcers or loss of gum tissue between teeth, fever, and swollen lymph
nodes.

Screening and Diagnosis

The dental examination will include a search for inflammation of the gums,
destroyed gum tissue, and crater-like ulcers in the gums that may harbor
plaque and debris from food. The exam might also include
dental and facial X rays.

Treatment and Therapy

Treatment options for ANUG include antibiotics to clear up the infection,
dental surgery, an improved diet and diet changes, and regular dental cleanings.

Prevention and Outcomes

To help reduce the chance of getting ANUG, one should maintain a balanced, nutritional diet and should take proper care of teeth and gums, which includes regular dentist visits.

Bibliography

Contreras, A., et al. “Human Herpesviridae in Acute Necrotizing Ulcerative Gingivitis in Children in Nigeria.” Oral Microbiology and Immunology 12 (1997): 259-265.

Langlais, Robert P., and Craig S. Miller. Color Atlas of Common Oral Diseases. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2009.

The Merck Manuals, Online Medical Library. “Actinomycosis.” Available at http://www.merck.com/mmhe.

Schreiner C., and F. B. Quinn. “Stomatitis.” University of Texas, Medical Branch. Available at http://www.utmb.edu/otoref/grnds/stomatitis.htm.

Sutton, Amy L., ed. Dental Care and Oral Health Sourcebook. 3d ed. Detroit: Omnigraphics, 2008.

What are antianxiety medications? |

Introduction

More people develop anxiety disorders than any other mental health problem. In part, this is because there are many types of anxiety disorders, including generalized anxiety disorder (GAD), panic disorders, social anxiety, and post-traumatic stress disorder (PTSD). Individuals with anxiety disorders can be treated with psychotherapy, medication, or a combination of the two. When medications are used, they tend to be either antidepressants or anxiolytics. Antidepressants are used to treat anxiety disorders as well as depression, because both of these disorders often exhibit a lack of neurotransmitters in the cells within the brain. It has been shown that when people exhibit anxiety, there is increased activity within the amygdala (part of the limbic system). Increased presence of neurotransmitters has been correlated with decreased activity in the amygdala and decreased anxiety. Bothselective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been used to treat depression and certain anxiety disorders. SSRIs, such as paroxetine (Paxil), fluoxetine (Prozac), and escitalopram (Lexapro), increase the amount of serotonin in the cells of the brain by inhibiting (preventing) their reuptake. SNRIs, including venlafaxine (Effexor) and duloxetine (Cymbalta), inhibit the reuptake of both norepinephrine (noradrenaline) and serotonin. Increasing the amounts of both of these neurotransmitters improves transmission of impulses along the neuron, thereby improving affect and decreasing anxiety.

Anxiolytics

Anxiolytics is the term for a category of medications that are commonly used to treat generalized anxiety disorders and panic disorders. These drugs are sometimes referred to as minor tranquilizers, but this is somewhat of a misnomer as the mechanism of action for these medications is not really understood. However, it is felt that the effect of most anxiolytics is tied into the functioning of gamma-aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter that renders brain cells in the area of the amygdala less likely to respond to excitatory neurotransmitters, making individuals less likely to suffer from anxiety reactions.

Benzodiazepines are the most common type of anxiolytics. Diazepam (Valium), alprazolam (Xanax), and lorazepam (Ativan) are the most commonly used benzodiazepines in the United States. Benzodiazepines are typically used to treat anxiety for only short periods of time. They are often used as the first means of treatment for severe anxiety reactions. Individuals are not likely to remain on these medications for a long period of time because of severe side effects (including oversedation), dependence, and problems with withdrawal.

Other anxiolytics include azapirones and barbiturates. Azapirones, such as buspirone (BuSpar), appear to work by increasing the activity of serotonin in the brain. They work relatively slowly, taking two to four weeks to have an effect. Their chemical composition is dramatically different from that of most of the other drugs used to treat anxiety. They act more slowly, have fewer side effects, and are better tolerated. There are almost no reported cases of dependence or oversedation from azapirones. Barbiturates, including secobarbital (Seconal) and pentobarbital (Nembutal), were commonly used to treat anxiety in the past. Although their mechanism of action in treating anxiety is still unknown, it is believed that they also work on GABA reactors in the brain. They are generally considered to be sedative-hypnotics and as such have many adverse effects and great risk of dependence and withdrawal reactions. Therefore, with the advent of the newer anxiolytics, barbiturates have become much less commonly used in the treatment of anxiety disorders.

As with most categories of medication, there are some over-the-counter and natural remedies that have been used to treat anxiety. The nutritional supplement most commonly used to treat anxiety is GABA. Although this amino acid is produced naturally in the brain, if people have poor nutritional habits, they may not be ingesting adequate precursors for this inhibitory neurotransmitter. In such individuals, this nutritional supplement has been found to lessen symptoms of depression and decrease anxiety.

If a person has developed an anxiety disorder, many different types of treatment are available. Which treatment is chosen should always depend on characteristics of the individual as well as the type and severity of the anxiety disorder.

Bibliography

Bongiorno, Peter. Holistic Solutions for Anxiety & Depression: Combining Natural Remedies with Conventional Care. New York: Norton, 2014. Print.

Charney, D. S., S. B. Nemeroff, and S. Braun. The Peace of Mind Prescription: An Authoritative Guide to Finding the Most Effective Treatment for Anxiety and Depression. Boston: Houghton Mifflin, 2004. Print.

Colman, I., et al. “Psychiatric Outcomes Ten Years After Treatment with Antidepressants or Anxiolytics.” British Journal of Psychiatry 193 (2008): 327–31. Print.

National Institute of Mental Health. “Medications.” Bethesda: Author, 2002. Print.

Newman, M. G., and W. B. Stiles. “Therapeutic Factors in Treating Anxiety Disorders.” Journal of Clinical Psychology 62 (2006): 649–59. Print.

Pillay, N. S., and D. J. Stein. “Emerging Anxiolytics.” Expert Opinion on Emerging Drugs 12 (2007): 541–54. Print.

Swartz, Karen L. Depression and Anxiety: Your Annual Guide to Prevention, Diagnosis, and Treatment. Baltimore: Johns Hopkins Medicine, 2013. Print.

Tone, Andrea. The Age of Anxiety: A History of America's Turbulent Affair with Tranquilizers. New York: Basic Books, 2011. Print.

What are bacteria classifications and types?

Definition

Bacteria are small, primarily microscopic, single-celled
organisms defined as members of the group prokaryotes, which lack internal membrane-enclosed organelles such as a nucleus.

Microbial classification has its roots, like those of more evolved organisms (such as plants and animals), in the system originally developed by Swedish botanist Carolus Linnaeus in the mid-eighteenth century; such systems reflect the evolutionary relationships among these organisms as largely confirmed in DNA (deoxyribonucleic acid) studies during the latter half of the twentieth century. Members of the same genus are considered closely related and may even interbreed. Members within the same order or family are not as closely related, yet they still reflect a common ancestry. An example is that of the class Mammalia, which includes both humans and whales. The lowest levels of the taxonomic hierarchy are the genus and species, with their Latinized binomial nomenclature considered the scientific name.

The system is applied to bacteria in an attempt to bring a sense of order in defining genetic relationships: Members of the same genus are considered closely related, while members of different genera are considered relatively unrelated. Variants within the same species are designated as subspecies or serovars, representing variations in surface molecules.

However, naming and classification of bacteria have often drawn on historical aspects of the organisms, such as the person who first isolated or characterized the bacterium (Theodor Escherich) or the disease (cholera). Members of different genera may actually be variants of the same species; the pathogens Shigella, the etiological agent of bacterial dysentery, and Escherichia, which is associated with a variety of gastrointestinal or urinary tract infections, are really variations of the same species. Among the reasons for the confusion in taxonomy is the instability of genetic material.

Bacteria have the ability to carry out horizontal transfer of genetic material:
Large segments of DNA readily pass or are exchanged not only among different
genera but also among different orders. In this manner, not only do the genetic
characteristics of bacteria change, but harmless organisms may acquire the ability
to cause disease. Despite these shortcomings of bacterial taxonomy, modern genetic
analysis has resulted in more accurate classification that reflects the
relationships among bacteria. Also, new names for genera as the underlying
molecular biology of microorganisms becomes better understood.

Bacteria are classified into two general categories, depending upon their cell-wall structure: gram-positives, which have a wall predominately composed of peptidoglycan (polysaccharide and protein), and gram-negatives, which have a cell wall composed primarily of lipopolysaccharide (lipids and polysaccharides). Gram-positives include members of the phylum Firmicutes, while gram-negatives represent most of the rest. The gram “characteristic” is named for Hans Christian Gram, a nineteenth and twentieth century German scientist.

Natural Habitat and Features

Organisms that are etiological agents of disease generally associate with the
host in two ways: as members of the normal flora, or microbiota, or as pathogens that must enter the body
through “openings” such as respiratory passages (the nose or mouth), the
gastrointestinal tract, or the genitourinary tract.

Resident pathogenic bacteria survive in the host primarily within niches that allow their survival. For example, the skin provides both a natural barrier to sterile regions within the body and a surface environment inhibitory to many types of microorganisms. The secretion of fatty acids in sebum creates an environment of low pH (acidity), and the secretion of NaCl (sodium chloride, or salt) in body sweat creates an environment of high salt. Organisms that become part of the microbiota on the skin, primarily members of the staphylococci and certain streptococci, must be able to survive under these conditions.

The microbiota of the colon consists of large numbers of primarily anaerobic, nonpathogenic bacteria, with an estimate of about one thousand bacteria in one gram of feces. Competition from the resident flora is generally sufficient to prevent transient pathogens from becoming established. In turn, anything that disrupts the resident flora can allow pathogens to become established. For example, the use of broad-spectrum antibiotics may remove the normal bacteria in the colon. Clostridium difficile, commonly present in a dormant spore state in the colon, can establish itself under these conditions and produce toxins that result in severe ulcerative colitis.

To carry out infection, pathogenic bacteria must exhibit characteristics
that not only allow transmission between hosts but also allow them to survive and
colonize within the new host. Such features are referred to as virulence factors, and they represent whatever means bacteria use to resist
the host defenses and to produce the symptoms of disease. The most obvious
examples are those of toxins, which are placed in two general categories: endotoxins, pharmacologically active chemicals that compose a portion of the
lipid component of the cell-wall structure of gram-negative bacteria, and exotoxins, which are secreted by some, primarily gram-positive, bacteria.
Other virulence factors include a polysaccharide or protein capsule that surrounds
some bacteria and prevents destruction by white blood cells (phagocytes) of the
host’s immune system, and fimbriae, hairlike structures on the cell surface that
allow attachment and colonization in the host.

Pathogenicity and Clinical Significance

The transmission of bacteria varies significantly and depends upon the
environmental niche of the organism in the host. Respiratory infections such as
whooping
cough or tuberculosis are transmitted through
respiratory secretions, such as droplets resulting from sneezes or coughs, which
are inhaled by the recipient. Sexually transmitted diseases such as
gonorrhea or syphilis are passed through sexual
contact. Some illnesses, such as staphylococcal infections, may be
transmitted by direct contact or by ingestion of contaminated foods.

Staphylococci. Members of the family Staphylococcaceae, a group of gram-positive cocci, include some of the most common pathogenic organisms that also can produce some of the most deadly infections. There are more than forty species of Staphylococcus, most of which are harmless. The two species of clinical importance are S. epidermidis, a member of the skin microbiota, and S. aureus, commonly found on the skin and nasal passages.

The staphylococci are differentiated from the streptococci, which they
physically resemble, by their ability to produce catalase, an enzyme that, when
mixed with peroxide, produces bubbles of oxygen. S. aureus in
particular has the ability to be a significant pathogen because of the large
variety of toxins various strains may produce. Most strains of S.
aureus produce several forms of coagulase, an enzyme that causes serum
to clot and that may play a role in the formation of boils. In addition, various
strains may produce enzymes that lyse red blood cells (β-hemolysins), may produce
white blood cells (leukocidins), and may induce severe shock (toxic shock syndrome
toxin). The experience with which most persons encounter the staphylococci is in
the form of what is commonly known as food poisoning, the result of exposure
to a heat-stable staphylococcal enterotoxin.

Streptococci. The streptococci are gram-positive cocci that physically resemble the staphylococci, but are genetically different and are differentiated from the latter by their lack of production of catalase. The streptococci is a large and diverse collection of species that were originally classified into groups by Rebecca Craighill Lancefield in the 1930’s on the basis of surface carbohydrates; the Lancefield classification scheme is still used.

Group
A, which includes Streptococcus pyogenes (“pus-creator”), is the
most important of the streptococci. Most commonly associated with strep throat,
infection with S. pyogenes can potentially lead to
rheumatic
fever or glomerulonephritis. S. pyogenes can
produce a variety of toxins, any of which may contribute to virulence. Such toxins
include enzymes that can lyse red blood cells (streptolysins) and can cause
impetigo, erythrogenic toxins (scarlet
fever), and severe shock (toxic shock syndrome toxin). Other
species of streptococci may contribute to the formation of dental carries
(S. mutans) and to meningitis in infants (group B S.
agalactiae). S. pneumoniae is a common cause of
bacterial pneumonia, and before the discovery of antibiotics,
it was associated with a high proportion of deaths in the elderly.

Enteric bacteria. The family Enterobacteriaceae, more commonly
called the enteric bacteria, is a diverse group of gram-negative bacteria that are part of the
microbiota of the intestinal tract in both warm-blooded and cold-blooded
organisms. Not all are pathogens, however. Most provide a benefit to the host by
suppressing the colonization of pathogens while at the same time producing B and K
vitamins for that host.

The species perhaps best known to the general public is Escherichia coli. Most types of E. coli are harmless. However, some types or strains have acquired the ability to invade host intestinal cells or to produce a variety of enterotoxins associated with food poisoning.

E. coli infections are routinely classified on the basis of the
type of disease and are placed in the following five categories: enterotoxigenic,
which causes the illness commonly referred to as travelers’
diarrhea, the result of two forms of toxins produced by this
strain, one of which is nearly identical to that associated with cholera;
shiga-toxin-producing, which produces a toxin that likely originated with
Shigella, the cause of bacterial dysentery (the most noted
strain is E. coli O157:H7, which produces a potentially
life-threatening hemolytic anemia); enteropathogenic, which is a cause of
severe diarrhea in infants; enteroinvasive, which is capable of invading
intestinal cells; and enteroaggregative, which is associated with chronic diarrhea
in persons in developing countries.

Salmonella and Shigella are the two other major
pathogens among the enterics. Salmonella
is a common contaminant of cold-blooded animals, birds, and
ruminants such as cattle and sheep. The most common result of infection in humans
is severe enterocolitis, usually the result of fecal contamination of
food or water. Historically S. typhi was the etiological agent of
typhoid
fever, a significant cause of mortality in cities in which
sewage was untreated. Shigella is the cause of bacterial
dysentery, a disease also transmitted through contaminated food or water.

Another enteric, Yersinia pestis
, is the agent of bubonic plague, a major killer between
the fourteenth and nineteenth centuries. Plague is endemic to many rodents and is
transmitted to humans through the bite of a flea.

Clostridia. The clostridia are gram-positive rods that form spores, allowing them to survive in the soil or as part of the intestinal microbiota. While most are nonpathogenic, helping to degrade organic material, several are important pathogens because of the toxins they encode. The diseases they cause are in part the result of their being strictly anaerobic (oxygen free).

C. tetani spores are ubiquitous. If they enter a cut or wound, or
any anaerobic environment, the spores may germinate, producing a toxin associated
with tetanus. If the infected person has not been immunized
against the toxin, the disease produces a loss of control of motor neurons,
resulting in a spastic paralysis (lockjaw). Botulinum toxin, produced by
C. botulinum, is among the most potent toxins known. While
rare, botulism poisoning usually results from canned vegetables
that have not been properly sterilized.

Campylobacter and Helicobacter, members of the ε-Proteobacteria, are among the most recently discovered pathogens. Campylobacter
is an important cause of infant diarrhea, particularly in developing countries. Helicobacter
infections of the stomach were found to be associated with the development of stomach ulcers. As a result of this connection, the treatment of ulcers with antibiotics rather than with palliative methods (antacids) was found to be more effective in preventing ulcer recurrence.

Drug Susceptibility

Toxic substances such as mercury, which could be used to treat diseases such as syphilis, have been known since the seventeenth century. However, the concept of a “magic bullet,” a safe antimicrobial agent that would kill germs and cure disease, dates to the 1880’s, when the germ theory of disease was evolving. The first success in this area of research was the arsenic compound salvarsan, developed by German physician Paul Ehrlich, who was able to successfully treat syphilis with the compound. However, this also was too toxic for general use. Arguably, the primary impetus in researching antimicrobial drugs grew from the enormous number of casualties of World War I, in which infection was as likely to result in death as was the wound itself.

The first success in antimicrobial therapy was the discovery of sulfa drugs by German physician Gerhard Domagk. Working closely with the dye industry in the 1920’s and 1930’s,
Domagk discovered that sulfur derivatives, the sulfonamides, could kill
streptococci, among the deadliest of bacteria. German
dictator Adolf Hitler and the Nazi Party limited research to finding ways to
improve the effectiveness of the drugs, and it was not until after World War II
that the full potential of sulfa drugs was seen. Meanwhile,
penicillin, discovered by British scientist Alexander
Fleming in 1928, became the first broad-spectrum antibiotic effective against most
major bacteria.

Antimicrobials fall into four general categories: analogs such as the sulfa drugs, which block DNA replication; inhibitors of cell-wall synthesis, such as the penicillins, cephalosporins, and vancomycin; inhibitors of cell-membrane function, such as polymyxin; and inhibitors of bacterial protein synthesis, such as tetracycline, chloramphenicol, streptomycin, and erythromycin.

Bacteria have evolved a variety of means to resist antibiotic functions. In some cases, resistance is a natural function of bacterial structure. For example, the penicillins inhibit cross-linking of the cell-wall peptidoglycan in gram-positive cells such as the staphylococci and streptococci. Because most gram-negative bacteria such as E. coli and Salmonella have cell-wall structures containing limited amounts of peptidoglycan, historically they were more resistant. Some bacteria have acquired genetic information to produce enzymes that destroy or inactivate antibiotics. In particular, most staphylococci have developed a penicillinase that inactivates penicillin, rendering the drug useless. Other bacteria have acquired genetic information to enzymatically modify other antibiotics. Bacteria may also become resistant by changing the target of the drug; altered ribosome structures confer resistance to erythromycin or streptomycin. Likewise, bacteria may acquire mechanisms to pump the antibiotic out of the cell.

Bibliography

Brooks, George, et al. Jawetz, Melnick, and Adelberg’s Medical Microbiology. 25th ed. New York: McGraw-Hill, 2010. A medical text that summarizes the major groups of pathogens, with concise descriptions of virulence factors associated with disease.

Hager, Thomas. The Demon Under the Microscope. New York: Harmony Books, 2006. Story behind the first “miracle drug,” the sulfa drugs that were effective in treating streptococcal infections. Largely a biography of Gerhard Domagk, their discoverer, the story also delves into antibiotic research and the politics and economics behind the work.

Koch, Arthur L. The Bacteria: Their Origin, Structure, Function, and Antibiosis. Bloomington, Ind.: Springer, 2006. Evolutionary history of bacteria. Focuses on how the evolution of the cell-wall structure led to the diversification of bacterial species.

Murray, Patrick, et al., eds. Manual of Clinical Microbiology. 9th ed. Washington, D.C.: ASM Press, 2007. Provides extensive coverage of pathogenic bacteria and mechanisms of disease. The detailed discussions are not for the casual science reader, but the book does serve as an excellent resource for the subject.

Singleton, Paul. Bacteria in Biology, Biotechnology, and Medicine. 6th ed. New York: John Wiley & Sons, 2004. A concise description of bacteria and their roles in nature. Included are chapters on bacterial structure, staining, and methods of classification and identification.

Willey, Joanne, et al. Prescott’s Microbiology. 8th ed. New York: McGraw-Hill, 2011. Outstanding textbook of microbiology. Specific chapters detail the most important organisms, including pathogens. The authors summarize pathogenic mechanisms in amanner that will not overwhelm readers.

What are free radicals? |

Exposure routes: The pathologically related free radicals originate within the body as a product of normal aerobic metabolic processes and inflammatory reactions, but some environmental agents, such as radiation and pollutants, with diverse routes of exposure, can increase the production of free radicals.

Where found: Free-radical-generating agents are diverse, as are their sources. The most common are tobacco smoke, sunlight, X rays, and automobile exhausts. Others include the carcinogens benzene, inorganic arsenic compounds, cadmium compounds, aflatoxins, and asbestos.

At risk: Populations at highest risk are those with a low dietary intake of antioxidants or genetic deficiencies in antioxidant enzymes (for example, glutathione peroxidase) or deoxyribonucleic acid (DNA) repair mechanisms, along with tobacco smokers, people who spend a long time in areas of heavy traffic or who are directly exposed to sunlight, and those with chronic inflammatory conditions.

Etiology and symptoms of associated cancers: The carcinogenic potential of free radicals arises from their ability to damage DNA, modify proteins by oxidation, and induce lipid peroxidation. The most frequently found form of oxidative DNA damage is hydroxylation of purine and pyrimidine bases. Other consequences of free radical actions for DNA are the generation of strand brakes, deamination, and formation of etheno adducts. Oxidative modifications of proteins include nitration, nitrosylation, and acetylation, among others. In addition, one of the most damaging effects of free radicals is lipid peroxidation because of its self-propagating nature, which greatly affects the properties and functioning of cell membranes. Furthermore, lipid peroxidation products, such as the reactive aldehydes malondialdehyde and 4-hydroxynonenal, can damage DNA and proteins in the same way as free radicals.

DNA oxidative damage can cause mutations in cancer-related genes, such as tumor-suppressor genes or oncogenes, and lead to the initiation and progression of cancer. Likewise, carcinogenesis can be induced by post-translational oxidative modification of proteins involved in the regulation of cell growth, signal transduction pathways, DNA repair, or other mechanisms of cellular homeostasis. For instance, free radicals are known to induce the transcription of the proto-oncogenes
FOS (also known as c-fos), JUN (c-jun), and MYC (c-myc), which stimulate cell growth. Also, posttranslational oxidative modifications of TP53 (p53), a tumor-suppressor protein, can inhibit its antiproliferative activity. Lastly, free radicals can promote not only tumor growth but also tumor migration and metastasis, by activating matrix metalloproteinases and stimulating the release of vascular endothelial growth factor. A current view of free radical actions supports the notion that these species do not act in a purely stochastic manner but are second messengers in redox-sensitive mechanisms of regulation of gene expression and enzyme activity. Aberrant and sustained redox signaling in oxidative stress situations leads to pathological changes, including cancer.

History: The relevance of free radicals in biological systems was first proposed by Denham Harman in 1956 in his classic article “Aging: A Theory Based on Free Radical and Radiation Chemistry.” Harman viewed age-related diseases as the result of an accumulation of oxidative damage. In the same year, in vitro studies showing the ability of oxygen reactive species to induce chromosome fragmentation in the presence of iron suggested for the first time the hypothesis of free-radical-induced carcinogenesis. Since then, the concept has been extended and free radicals have been found to be involved in most pathological conditions.

Alschuler, Lise, and Karolyn A. Gazella. The Definitive Guide to Cancer: An Integrative Approach to Prevention, Treatment, and Healing. 3rd ed. New York: Celestial Arts, 2010. Print.

Farooqui, Tahira, and Akhlaq A. Farooqui. Oxidative Stress in Vertebrates and Invertebrates: Molecular Aspects on Cell Signaling. Hoboken: Wiley, 2012. Print.

Halliwell, B. “Oxidative Stress and Cancer: Have We Moved Forward?” Biochemistry Journal 401 (2007): 1–11.

Hussain, S. P., L. J. Hofseth, and C. C. Harris. “Radical Causes of Cancer.” Nature Reviews. Cancer 3 (2003): 276–85.

Shankar, Sharmila, and Rakesh Srivastava. Nutrition, Diet, and Cancer. New York: Springer, 2012. Print.

Wu, W. S. “The Signaling Mechanism of ROS in Tumor Progression.” Cancer Metastasis Reviews 25 (2006): 695–705.

How can one deal with lack of discipline in the classroom?

There are limits to what teachers can do to maintain discipline in a classroom. Many of the factors that affect classroom behavior, including home environment, class size, and even student personalities, are beyond the control of the teacher. 

The first thing you need to do is set clear boundaries and guidelines. Often children (especially teens), as part of their own attempts to build independent identities, will push the limits of any rules or conventions; making...

There are limits to what teachers can do to maintain discipline in a classroom. Many of the factors that affect classroom behavior, including home environment, class size, and even student personalities, are beyond the control of the teacher. 

The first thing you need to do is set clear boundaries and guidelines. Often children (especially teens), as part of their own attempts to build independent identities, will push the limits of any rules or conventions; making rule systems transparent, fair, and consistently enforced actually gives the students a sort of stability that they find reassuring. This means that all classroom rules should be simple, clear, explained to students in terms they can understand, and enforced. 

Next, students with disabilities or behavioral problems should be referred to the appropriate staff to get the treatment they need. Accommodation plans for special needs students will reduce the likelihood that they will become discipline problems. 

Rules and punishments for infractions should conform to all relevant school and departmental guidelines. The better the support you have from upper administration, the more effectively you will be able to maintain discipline through methods such as reporting, detention, suspension, and parental involvement.

As a teacher, you should remain calm and professional at all times, creating an orderly and focused classroom that engages student interest. When students do push boundaries, avoid arguing with them or losing your temper, but remain calm, cheerful and firm. Enlist your students to work with you to create a positive classroom environment. Be aware of what is going on in every part of your classroom so that you can deal with potential problems before they escalate. Praise and positively reward good behavior.

How does smoking affect pregnancy?

Risks for Mother and Baby

Researchers do not yet fully understand how every chemical in tobacco smoke affects a growing baby, but they do know that the health risks are high. If an expecting mother smokes, she is more likely to have pregnancy complications that put both herself and the baby at risk. Such complications may be pelvic pain; early rupture of the membranes; placental problems (detachment, tearing, or slipping); stillbirth; premature births; and miscarriages. According to 2011 data accumulated from twenty-four states by the Pregnancy Risk Assessment and Monitoring System, about 10 percent of women said that they had smoked during the final three months of their pregnancy.

Smoking while pregnant also puts the baby at a higher risk for serious complications, such as being born underweight, which is a sign that the baby has not adequately developed. According to the Centers for Disease Control and Prevention in 2014, one in every five babies of mothers who smoke while pregnant is born underweight. This puts the baby at high risk for serious health issues, including intellectual disability, cerebral palsy, and lung problems. Babies are also at a greater risk for sudden infant death syndrome (SIDS) and developing attention deficit and hyperactivity disorders.

It is also important to note that because the baby is exposed to nicotine through the placenta, smoking while pregnant can cause the baby to have nicotine withdrawal symptoms after birth. This can make the baby more jittery, nervous, and harder to soothe. The earlier an expectant mother stops smoking, the better it is for the baby and for the mother’s own health. Even shortly after stopping, an expectant mother will begin to recover. For example, within minutes, heart rate and blood pressure will drop. Within twelve hours, carbon monoxide levels in the blood return to normal (carbon monoxide decreases the level of oxygen in the body). Within just a couple of weeks, circulation and lungs improve their function.

In addition, smokers that breastfeed continue to pass chemicals like nicotine on to the baby through breast milk. Babies are also very susceptible to secondhand smoke. According to the American Lung Association in 2015, exposure to secondhand smoke causes 430 SIDS deaths in the United States annually.

Quitting Smoking

After an individual quits smoking, the body goes through withdrawal. The individual may experience symptoms such as dizziness, depression, headaches, tiredness, irritability, and sleep problems. Withdrawal effects, however, are temporary, and cravings can be overcome by simple distraction techniques. Some distraction techniques are participation in such activities as walking; relaxation methods, such as deep breathing; drinking water; nibbling on healthy snacks, such as vegetables and fruits; sucking on a hard piece of candy; investing time into a hobby; and simply talking with others who have successfully quit smoking.

In addition, certain programs and smoking cessation tools can help to gradually decrease nicotine levels. However, certain smoking cessation products such as nicotine gum or patches may not be safe to use while pregnant.

Bibliography

Anderson, Judith. It’s Your Health: Smoking. North Mantko: Smart Apple Media, 2005. Print.

"Health Effects of Secondhand Smoke." American Lung Association. Amer. Lung Assn., 2015. Web. 28 Oct. 2015.

How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Rockville: US Dept. of Health and Human Services, 2010. Print.

"Reproductive Health: Tobacco Use and Pregnancy." Centers for Disease Control and Prevention. CDC, 9 Sept. 2015. Web. 28 Oct. 2015.

Substance Abuse and Mental Health Services Administration. Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings. Rockville: US Dept. of Health and Human Services, 2010. PDF file.