What is the nature of temptation in the play Macbeth? What tempts him, and how does he handle this temptation?

Macbeth's tragic flaw is his ambition. What tempts him is the desire for power, which is whetted by the three witches prophesying that he will become King of Scotland.

The scenario unfolds as follows: Macbeth helps win a battle in support of King Duncan, and unbeknownst to him, the King declares him Thane of Cawdor as his reward. Macbeth, with Banquo, then encounters the witches on a wild heath and they address Macbeth as Thane of Cawdor. They also say he "shalt be king hereafter."

Macbeth is startled and questions the witches, but they disappear.

When Macbeth finds out he is indeed Thane of Cawdor, this causes both him and Banquo to wonder whether the witches are also right that he will become king. Banquo warns Macbeth that the witches, who he calls "the instruments of darkness," may have told him one truth (about becoming Thane of Cawdor) to "betray" him and lead him down a dark path to his own destruction.  

The problem is that the words of the witches speak to Macbeth's deepest desire: to become king is the thing he wants. He wants to believe their words are true, and he and his wife yearn for him to be king so badly that they are not willing to wait for events to unfold naturally: they both believe they need to make it happen right away, through murder, because Duncan is staying with them and they don't know when the opportunity to kill him will arise again. Macbeth, even before consulting Lady Macbeth, is tempted with the "horrid image" of murdering Duncan, an image that "doth unfix [his]...hair [makes his hair stand on end]."

Macbeth handles the temptation badly by giving into it and murdering Duncan, his king, to whom he has pledged his loyalty. This is a deep betrayal. He is goaded on by his wife and the witches, but he himself is to blame for he gives in to the dark impulses inside himself: though he has a moment of struggle in which he thinks that once he steps over the line into murder, it will be all bloodshed for the rest of his life and no going back, he still does what he knows is wrong. 

In Act 2 Scene 5, what creates the tremendous tension in this scene from Romeo and Juliet?

Tension in Act II, Scene 5, is created by the Nurse, who seizes the opportunity to be the center of Juliet's attention and exploits this opportunity by teasing Juliet and delaying her answer so that she can have some attention herself. 

As the scene opens, Juliet waits impatiently for the Nurse to return with Romeo's notice about their wedding plans. Since Juliet has sent the Nurse at nine o'clock and now it is twelve, she complains that the nurse is still not back and is dilatory on purpose:

But old folks, many feign as they were dead;
Unwieldy, slow, heavy and pale as lead.
O God, she comes! (2.5.16-18)

But, when she enters, Juliet is further frustrated because the Nurse, taking advantage of being the center of attention, complains that she is tired and her bones hurt. Further, Juliet entreats her, "Is thy news good, or bad?"(2.5.5), but the Nurse again does answer; instead, she needles her about Romeo, saying, 

Well, you have made a simple choice; you know not
how to choose a man: Romeo! no, not he; though his
face be better than any man's....(2.5.38-40)

The silly, loquacious Nurse then speaks circuitously and make puns on decorated shoes and "courtesy/curtsy." And, again she resumes her complaints about her aches and pains. Finally, she gives Juliet the news, but not until she teases Juliet with verbose descriptions of Romeo's handsomeness, kindness, courtesy, virtue--everything but what Juliet wants to hear.

Finally, the Nurse asks Juliet if she has permission to go to confession at the church where Friar Lawrence is now. When Juliet replies that she does, the Nurse instructs her that the priest will perform the marriage ceremony there in the church. Jubilant, Juliet exclaims, "Hie to high fortune!" and happily rushes out.

How can I compare and contrast To The Lighthouse and Animal Farm?

To the Lighthouse was written by Virginia Woolf, a British author, after World War I. It was published in 1927. Animal Farm was also written by a British author (George Orwell) and published in 1945, at the close of the Second World War. 

Stylistically, the novels are quite different. Animal Farm is an allegory, which uses farmhouse scenery to make a critique of the politics of the Soviet Union. Its characters and plot are mostly important for their symbolic purpose--that is, for the way in which they recall actual people and political events in post-revolutionary Russia. 

To the Lighthouse, conversely, is a modernist novel, and as such its treatment of characters is extremely different. Rather than using characters to "stand in" for world political figures, it uses characterization, particularly through devices like internal monologue and "stream of consciousness" writing, to explore dimensions and elements of subjectivity, consciousness, and perception--that is, universal qualities of the human experience. 

To the Lighthouse, however, shares Animal Farm's concern about national politics and violence: though Animal Farm is much more overtly political, To the Lighthouse also records the death of two of its protagonists in the Second World War, and leaves the others to mourn their loss after the war is over. The novel is an oblique, rather than overt, critique of the national political power structures that create and perpetrate violence.

What are cancer vaccines?

Definition

Cancer vaccines are either preventive or therapeutic. Preventive, or prophylactic, vaccines prevent cancer from developing in healthy persons. Therapeutic, or treatment, vaccines treat existing cancer by strengthening the body’s immune response against the malignancy.

Immunotherapy

Vaccines are commonly known for their benefits in preventing
or fighting infectious diseases such as polio, tetanus, or measles. Vaccines, as a
form of immunotherapy, promote immunity, the body’s defense against pathogens and injured
or abnormal cells, such as cancer cells. The immune
system, which can deliver its effector components to different
locations in the body, is such a highly specific system that it can isolate one
cancer cell from a vast amount of other healthy cells and destroy that cancer
cell.

Utilizing basic principles of infectious disease vaccines, a new type of
vaccine is being developed to target one of the most critical public health
concerns: cancer. Although some advances have been made, cancer is
still the leading cause of death in persons younger than age eighty-five years in
the United States.

Cancer is a group of diseases characterized by abnormal and uncontrolled cell
growth, invasion, and sometimes metastasis. In a healthy body, cells
grow, die, and are replaced in a regulated fashion. Damage or change in the
genetic material of cells by internal or environmental factors sometimes results
in immortal cells, which continue to multiply until a mass of cancer cells, or a
tumor, develops. Most cancer-related deaths are caused by
metastasis, in which malignant cells make their way into the bloodstream and
establish colonies in other parts of the body. Cancer immunotherapy manipulates
the immune system to overcome self-tolerance and to recognize cancer cells.

Like the traditional vaccines that present inactivated, attenuated, or subunit
pathogens to the immune system, cancer vaccines present the
right cancer antigen in combination with the right adjuvant to generate
the right type of immune response. This response, whether humoral or cellular, ideally should destroy
the cancer only and leave healthy cells untouched. Cancer cells are different from
normal healthy cells. As such, they are recognized by the immune system as being
different. Proteins expressed by cancer cells are different from normal proteins
or are absent in normal differentiated cells. These proteins can be immunogenic
when presented in the context of a cancer vaccine.

The vaccine is made from cancer-specific proteins or proteins that are found
predominantly in cancer cells. Because of the associated immunologic memory, the
risk of recurrence is reduced compared with traditional treatments. Rather than
compromise the immune system, as many chemotherapy treatments do, cancer
vaccines train the immune system to target those specific malignant cells.
Consequently, some cancer vaccines are safer and do not have the traditional side
effects associated with chemotherapy or radiation therapy. Depending on the
specific vaccine, cancer vaccines might be stand-alone therapies or may be used
with other conventional cancer therapies.

Every cancer, and its vaccine, is different. Personalized medicine is critical to the development of vaccines that must be tailor-made to each person.

Passive and Active Immunotherapy

Cancer vaccines are characterized as either active or passive immunotherapies. While the active type aims to elicit the
host immune system to fight the disease, the passive type does not depend on the
body’s defenses to start the attack. Instead, it uses administered medicines
(antibodies or T cell therapy) to destroy the tumor. Passive
immunotherapy has no immunologic memory associated with the treatment. Any of
these therapies can be targeted to one type of tumor cell or antigen (specific
immunotherapies) or can generally stimulate the immune system (nonspecific
immunotherapies).

Cancer vaccines are either therapeutic or preventive. Therapeutic vaccines treat persons at early stages of the
disease or with minimal residual disease after removal of the main tumor. In some
cases, advanced disease may be treated with a vaccine. Preventive vaccines include the human papillomavirus
(HPV)
vaccine, which can prevent cervical, vaginal, and vulvar
cancers. The hepatitis B virus (HBV) vaccine lowers the risk of developing liver cancer. The
Helicobacter pylori
vaccine targets the bacterium H. pylori, which is
associated with stomach cancer. Hence, the HPV, HBV, and H.
pylori vaccines do not target cancer cells; rather, they are specific
to the viruses or bacteria that give rise to these cancers.

Vaccine Strategies

Cancer vaccines target malignancies such as melanoma, leukemia, and non-Hodgkin’s lymphoma, and cancers of the lung, breast, kidney, ovary, pancreas, prostate, and colorectal area. The unique complex strategies used in cancer vaccine design depend on various considerations particular to the specific cancer process, the optimum level of immunity that can potentially be achieved, and a person’s health status.

In whole cancer-cell vaccines, cancer cells are irradiated before they are returned to the treated person’s body through injection. These vaccines contain thousands of potential antigens expressed in the whole tumor. Antigen vaccines, however, use only one antigen (or a few), whereas peptide vaccines present short fragments of the tumor protein.

Dendritic cell vaccines use specialized antigen-presenting cells that are efficient in presenting tumor antigens and tumor peptides to the immune system. Dendritic cells break down cancer proteins into small fragments and then present these antigens to T cells, thus improving immunologic antigen recognition and, eventually, cancer destruction. Nucleic acid vaccines use the genetic code that codes for cancer protein antigens so that the host cells make the cancer antigen continuously while keeping the immune response stimulated and strong.

Viral and bacterial, vector-based, vaccines can deliver antigens or genes encoding the tumor proteins or peptides to make the host’s immune system more apt to respond. Because bacterial and viral components on these vector vaccines represent pathogen danger signals, they may trigger additional immune responses that might benefit the overall response, making it more robust and longer lasting.

Anti-idiotype vaccines can act passively against B-cell lymphomas or actively by mimicking cancer antigens. In the latter case, these vaccines work through antibody cascades. Some of these vaccines contain adjuvants to amplify either the humoral or the cell-mediated (or both) immune responses to an antigen and break self-tolerance. Adjuvants have been developed to enhance immunogenicity when mixed with proteins, peptides, or deoxyribonucleic acid (DNA).Tumor peptide-MHC (major histocompatibility complex) complexes are important for the recognition of tumor cells by the immune system because tumor peptides are recognized only if they are joined to the MHC complex. Cytotoxic T cells are the killer cells that recognize the peptide-MHC complexes on the tumor cells and destroy the cancer cells.

Impact

Cancer vaccines have the potential to treat cancers in line with treatments
such as surgery or radiation therapy. Cancer vaccines are mostly experimental,
although some have already entered the drug market after receiving U.S.
Food and Drug
Administration approval. Some vaccines have shown promise in
clinical trials, while others have advanced through late-stage clinical
studies.

Using cancer vaccines after the removal of the main tumor by traditional means helps lead the body’s own immune system to destroy any remaining cancer cells and to target metastasis. Immunotherapy has the potential to strengthen the body’s natural defenses, despite cancers that might have already developed, and it can prevent new growth of existing cancers, hamper recurrence of treated cancers, and destroy cancer cells not previously eliminated by other treatments.

When cancer is controlled or cured, cachexia usually stops. During cachexia, there is wasting of adipose and
skeletal muscle. Persons with pancreatic and gastric cancer, for example, suffer
from acute cachexia. Those with cachexia suffer from poor functional performance,
depressed chemotherapy response, and greater mortality. Therefore, the success of
cancer vaccine development may benefit persons with cachexia enormously.

Immunotherapies themselves are costly, but in the long term, they reduce overall medical costs by reducing fees for patient care, management, hospitalization, and death. The pursuit and development of safe and effective cancer vaccines can greatly benefit immunologists, oncologists, molecular biologists, chemists, public health workers, and society in general. Above all, they help persons with cancer.

Bibliography

Finn, O. J. “Cancer Vaccines: Between the Idea and the Reality.” Nature Reviews Immunology 3, no. 8 (2003): 630-641. A review that addresses unique and common challenges to cancer vaccines and the progress that has been made in meeting those challenges.

Jemal, A., et al. “Cancer Statistics, 2010.” CA: A Cancer Journal for Clinicians 60, no. 5 (2010): 277-300. This clinical report examines cancer incidence, mortality, and survival based on incidence data.

Murphy, J. F. “Trends in Cancer Immunotherapy.” Clinical Medicine Insights: Oncology 4 (July 14, 2010): 67-80. Discusses the attempts of cancer immunotherapy to redirect the power and specificity of the immune system toward effectively and safely treating malignancy.

Plotkin, Stanley A., Walter A. Orenstein, and Paul A. Offit. Vaccines. 5th ed. Philadelphia: Saunders/Elsevier, 2008. A comprehensive vaccination textbook covering the topics of development, production, safety and efficacy, morbidity, and mortality.

Raez, L. E., and E. S Santos. “Cancer Vaccines: A New Therapeutic Alternative for Lung Cancer Therapy?” Immunotherapy 1, no. 5 (2009): 727-728. An editorial that discusses challenges for lung cancer vaccine development and clinical activities.

Rosenberg, S. A., J. C. Yang, and N. P. Restifo. “Cancer Immunotherapy: Moving Beyond Current Vaccines.” Nature Medicine 10, no. 9 (2004): 909-915. Review of a cancer vaccine trial that highlights secondary strategies that facilitate cancer regression in preclinical and clinical models.

Schlom, J., P. M. Arlen, and J. L. Gulley. “Cancer Vaccines: Moving Beyond Current Paradigms.” Clinical Cancer Research 13, no. 1 (2007): 3776-3782. Reviews several different cancer-vaccine clinical trials and respective patient response and survival outcomes.

The Scientist.com. “Immune System Versus Cancer.” Available at http://www.the-scientist.com/2009/11/1/36/1. Article that underscores the role of the immune system in cancer within the context of immune surveillance.

Sonpavde, G., et al. “Emerging Vaccine Therapy Approaches for Prostate Cancer.” Reviews in Urology 12, no. 1 (2010): 25-34. Explores different prostate vaccine approaches with selecting proper patient populations, discovering optimal doses, and routes of administration for better outcomes.

How are imaging and radiology related?

Indications and Procedures

Before the advent of radiology, physicians were forced to rely on visual clues, palpation (examination by touch), and exploratory surgery to discover what lay beneath a patient’s skin. X-rays provided the first path around this limitation and allowed physicians to peer beneath the skin without surgery. X-rays are electromagnetic radiation similar to visible light, but they have much higher energies than visible light, which makes them more penetrating.

Circumstances under which a doctor needs to see inside the body and might use x-rays to do so include those in which a patient has fallen and experiences localized pain and swelling in the leg (possible broken bone); a patient with severe pain in the lower back passes blood in the urine (possible kidney stone); a patient experiences intermittent and squeezing chest pain, nausea, and shortness of breath (possible constricted arteries in the heart); and a patient has a history of localized stomach pain and heartburn, also called acid reflux (possible inflamed esophagus, hiatal hernia, or ulcer).

All medical imaging devices require a source of radiation, a detector, and a way to position the patient. For x-rays, the patient stands in front of a film holder or lies on a table over a film holder while x-rays from an x-ray tube pass through the patient and cast the patient’s shadow onto the film. The film must be as large as the body part being examined. Dense constituents such as bones show up as white on x-ray negatives, while various other body tissues show up as shades of gray depending upon the fraction of the x-rays that they block.

X-ray film has been developed to have excellent resolution and contrast, and an x-ray is a permanent record. It is not easy to take several x-rays in quick succession, however, as might be done to examine the upper gastrointestinal tract. An alternative is to use fluoroscopy, in which a screen coated with special compounds is used in the place of film. These compounds fluoresce when struck by x-rays. Advantages are that the image is immediate (no film to develop) and moving images can be viewed. The image can be made brighter by an image intensifier—a television-camera-like device that amplifies the image—and a permanent record can be made by photographing this final image.

An ultrasound
unit adapts sonar to medical purposes. The unit consists of a probe; electronics to generate, receive, and analyze signals; and a monitor to display the results. Such a device is relatively inexpensive compared with other types of scanners, and at the intensities used, ultrasound waves do not harm the body. The ultrasound probe contains a transducer, a crystal that can change electrical signals into sound waves and can also act as a receiver changing sound waves into electrical signals. During the examination, a gel is spread over the patient’s skin in the area of interest. The gel provides good acoustical coupling between the probe and the patient’s body tissue. To create an image of structures as small as 1 millimeter, ultrasound frequencies between 3 and 7 megahertz are used. The crystal inside the probe emits sound waves while rapidly rocking back and forth, producing a wedge of sound pulses. The crystal then becomes a receiver and picks up sound echoes that form as the sound passes from one type of tissue into another. Distance can be determined from the time elapsed between sending a pulse and receiving the echo. Combining this distance information with the direction and intensity of the echo allows a computer to build an image of the structures inside the body.

This image is displayed on a monitor screen and can also be printed for a permanent record. The probe is moved around to provide the least obstructed view of the target. Since ultrasound waves pass easily through soft tissues such as the liver and fluid-filled organs such as the gallbladder or the uterus during pregnancy, ultrasound is particularly useful to examine these organs. Ultrasound does not penetrate bone or gas, and the latter property makes it difficult to examine the digestive tract with ultrasound.

Like ultrasound, magnetic resonance imaging (MRI), uses no potentially harmful radiation, but it is the most expensive of the imaging techniques. MRI uses a very large, superconducting magnet. Once the magnetic field is established, superconducting magnets require very little electrical power. To be superconducting, the magnet is wound with niobium-titanium wire and maintained at liquid helium temperature (about five kelvins above absolute zero). The magnet itself is in the form of a very large, hollow cylinder into which the patient can be inserted. The magnetic field inside the cylinder is uniform and very strong, typically 0.5 to 2.0 tesla; for comparison, the strength of the earth’s magnetic field is only about 0.00005 tesla near the surface. There are also three sets of much smaller (.0018 to .0027 of a tesla) “gradient” magnets, which are used to tweak the magnetic field at pinpoint locations during the scan. Hydrogen atoms are among the most abundant atoms in soft tissue. In a strong magnetic field, the spin axis of hydrogen nuclei (protons) precesses about magnetic field lines. The exact frequency with which it precesses depends on the proton’s surroundings, or the type of tissue in which it is found.

The patient rests on a table that moves into the tunnel formed by the magnet. The magnetic field causes no noticeable sensation, but claustrophobic patients may become anxious. To combat this effect, newer machines have wider tunnels or have one side open. An insulated wire coil may be placed on the patient over the area to be examined, or coils mounted on the magnet may be used. A brief pulse of radiofrequency waves is broadcast from the coil at the same time that the gradient magnets adjust the magnetic field to the right value in a narrow slice of the patient. If the radiofrequency is at the precession frequency, then those protons with which it resonates will absorb energy. After the radiofrequency pulse, the protons produce an echo that radiates energy back to the coil. Analysis of this energy allows the identification of the type of tissue, which, along with location information from the gradient magnets, allows a computer to construct an image of the internal tissues of the patient. The image can be either two-dimensional or three-dimensional, as needed. Two-dimensional slices can be vertical, horizontal, or in any plane desired.

A scan of the brain and spinal column can detect areas of damage to the myelin (insulating sheath) surrounding nerve fibers that is the hallmark of multiple sclerosis. MRI scans are also used in diagnosing tumors, infections of the brain, strokes, torn ligaments, and many other conditions. As with x-rays, contrast agents may be injected into the patient to make certain tissues or systems stand out. For example, the blood vessels in the heart may be examined in this fashion. Depending upon the size of the region to be scanned, the procedure takes from twenty to ninety minutes, and the patient must remain as still as possible during this time. Currents in the gradient magnets produce loud thumping sounds. These may be masked by providing the patient with music through earphones during the examination. Physicians now depend heavily on MRI investigations, and the 2003 Nobel Prize in Medicine or Physiology was awarded to Paul C. Lauterbur and Sir Peter Mansfield for their work leading to the development of the MRI technique.

A nuclear medicine
scan, also called nuclear radiology
or isotope study, uses radioactive pharmaceuticals that have been injected into or ingested by the patient. The radiation dose to the patient is strictly controlled and is the least possible for the procedure to be effective. The radioactive isotopes used emit gamma rays—essentially high-energy x-rays—which easily pass through the body and are observed by an array of gamma detectors. The patient lies on a table while the detector array is positioned near the target organ. In some applications, the array slowly scans a region. A computer receives information on the location and intensity of the detected gamma rays and constructs an image from this information. The image is fuzzy and lacks the fine detail that can be seen with x-rays or ultrasound, but it shows directly how well the target organ functions.

To be useful for this purpose, radioactive isotopes
must emit penetrating gamma rays, have a short half-life, and either be taken up by the target organ or be capable of being attached to a molecule that is taken up by the target organ. A short half-life is desirable to ensure that the isotope will cease to be radioactive not too long after it has served its purpose. Technetium-99m is frequently used because it is taken up by the thyroid and salivary glands (if those are the targets), it can be used to tag other biologically active molecules, and its half-life is only 6.01 hours.

For a thyroid study, the patient may be given a drink or a pill containing iodine-123 (13.1 hour half-life). About twenty-four hours later, the gamma emission from the thyroid is measured. This procedure shows how well the thyroid works in general. The patient may then be injected with technetium-99m and several scans made over the next hour. This provides another measure of the thyroid’s functioning. It also allows a measure of the thyroid’s size and shape. Any area of inactivity suggests a blockage or damage, while an unusual area of activity suggests an abnormally high tissue growth rate such as a tumor. In general, a region of rapidly growing tissue shows up as a hot spot on a nuclear medicine scan, which makes it possible to see a healing bone fracture that an x-ray might miss.

A positron emission tomography (PET) scan is a special type of nuclear medicine scan that capitalizes on a property of the gamma rays emitted during positron annihilation. Positrons are positively charged and are the electron’s antiparticle. Since they are oppositely charged, positrons and electrons are strongly attracted to each other, and as soon as they touch, they mutually annihilate, converting their energy into two gamma rays emitted at precisely 180 degrees to each other.

A gantry houses a large ring of gamma ray detectors arranged like a doughnut on its side. The patient rests on a movable table that carries the patient into, and perhaps through, the detector ring. Depending upon the purpose of the examination, one of several radioactive pharmaceuticals is administered. For example, fluorine-18 (half-life 109.8 minutes) is attached to glucose molecules and used to monitor the brain’s metabolism. Since active areas of the brain draw the most glucose, a PET scan can watch the brain at work. When a fluorine nucleus emits a positron, the positron encounters an electron almost at once and is annihilated. The gamma ray detectors continually register hits from natural background radiation, but if two detectors located 180 degrees around the ring from each other record gamma rays of the right energy (0.511 million electron volts) and within a few nanoseconds of each other, it is virtually certain that they originated from a positron annihilation in the patient. A computer then draws a straight line between the two detectors and through the patient. Where two or more lines intersect is the location of the activity.

A single photon emission computed tomography
(SPECT) scan is similar to a PET scan, but it detects only one photon at a time instead of a pair. To define the direction of a gamma ray photon, a collimator is placed in front of the detector array. The collimator is a slab of five-centimeter-long lead straws pointing at the patient so that a gamma ray can reach the detector only by traveling up a straw. Such a collimator and detector array is called an Anger camera. A ring of cameras around the patient allows a computer to construct a three-dimensional image of the target organ. SPECT combines the organ function information of nuclear medicine with some of the resolution of a computed tomography (CT) scan.

The CT apparatus consists of a movable table on which the patient rests and a gantry that houses the x-ray equipment. A doughnut hole in the gantry is large enough for the patient and table to pass through. An x-ray tube is mounted in the doughnut, and an array of x-ray detectors are mounted in the doughnut directly opposite from the x-ray source. As the doughnut rotates all the way around, the x-ray beam is sent through a narrow “slice” of the patient. Instead of the normal x-ray silhouette of the patient as illuminated from one direction, silhouettes from all directions are obtained, but only as numbers, not yet as images.

The information available consists of where the detector was when it picked up the signal and how strong the signal was. As the scan continues, the computer uses this information to construct an image of that slice of the patient. While the doughnut carries the x-ray tube and detectors around and around the patient, the table advances slowly and continuously until the whole body (or the desired segment) has been scanned. Blood clots and ruptured vessels in the brain are easily detected, as well as tumors in soft tissues such as the liver.

Uses and Complications

Bones, bone breaks, and some tumors show up well on an x-ray, but soft tissue images may require additional techniques. For examination of the upper gastrointestinal tract, the patient is given a barium solution to drink while standing in front of the x-ray detector. Barium blocks x-rays and coats the esophagus and stomach lining, thereby outlining them in detail on the x-ray. In the “barium swallow,” a quick series of x-rays is taken to follow the progress of the barium into the stomach. Constrictions in the esophagus, the action of the stomach valve, and the presence of a hiatal hernia
(the upper part of the stomach bulging through a weakened diaphragm) become visible. As the barium proceeds, a stomach ulcer may stand out in outline.

To check for kidney stones
and to examine the kidneys, ureters, and urinary bladder, an intravenous pyelogram (IVP) is performed. First, a contrast solution (based on iodine, which blocks x-rays) is injected into the patient’s vein. The patient may feel a brief warm flush as the body reacts to the iodine, but this reaction passes quickly. The solution used soon passes through the patient’s system: through the kidneys, through the ureters, and to the bladder. A series of x-rays is then taken in which kidney stones may be revealed; any swelling of a kidney or blockage of a ureter will show up, if present.

The angiogram, a similar but more extensive procedure, is used to examine the blood vessels of the heart or other location. In this procedure, a catheter (fine plastic tube) is inserted into the femoral artery at the groin or into a blood vessel in the upper arm. The patient is given medication for pain and anxiety. Using a fluoroscope monitor, the physician maneuvers the catheter to the desired location and then injects the contrast solution through the catheter. Several x-rays are taken from various angles, and any blockages or constrictions are generally apparent. The catheter is then withdrawn, and the patient is required to rest.

CT scanning represents a major step forward in x-ray technology. A patient might suffer a sudden loss of muscle control and feeling in part of the body (possible stroke). The doctor would like to x-ray the brain for signs of a ruptured or blocked blood vessel, but contrast agents are not useful for the brain. Without them, internal organs and tissues appear only as faint ghosts in an x-ray. A CT scan uses computer technology to convert special x-ray images into clear views of the organs.

While prudence dictates that radiation exposure be kept to a minimum, the medical benefits of procedures using radiation generally outweigh the risks. Provided that a radiation dose is not overwhelmingly massive, the body has amazing recuperative properties and is able to repair most radiation damage. Everyone is exposed daily to background radiation from naturally occurring trace amounts of radioactive elements and from cosmic rays. None of the typical imaging procedures generates radiation above allowable limits, but it should be noted that a medical procedure may expose the target organ to many times the average body dose.

A typical x-ray image shows different types of tissue as various shades of gray. Advances in medical imaging include digitizing any image and using powerful computer programs to enhance the subtle differences between different types of tissue, even coloring them so that they are immediately obvious to the physician. Three-dimensional images can be constructed and rotated so that they can be examined from every angle. A physician can see exactly what problems will be encountered in removing a tumor. Computers can scan x-rays used to screen for breast cancer, called mammograms, and draw the radiologist’s attention to any questionable regions. Finally, computers can merge images from complementary techniques such as PET (shows functionality of the organ) with MRI (shows high-resolution detail) to give a more complete view.

Perspective and Prospects

On November 8, 1895, Wilhelm Conrad Röntgen
made an astounding and disquieting discovery. Many scientists of the day, including Röntgen, were studying cathode rays. The required apparatus was an evacuated glass tube with electrodes sealed inside at either end. When a high voltage was placed across the electrodes, cathode rays (electrons) streamed from the cathode, and where they struck the glass tube, the glass fluoresced.

Röntgen covered the tube with black paper and darkened the room, but still a fluorescent screen some distance away from the tube glowed whenever he operated the tube. Since cathode rays cannot travel far through air, Röntgen deduced that some unknown type of radiation must be coming from the tube. He called it X radiation (X for unknown). Placing bits of wood or metal between the tube and the screen cast shadows on the screen, some darker and some lighter. The key moment came when Röntgen held up a small lead disk. The expected shadow of the lead appeared, but holding the disk, Röntgen saw the shadows of his finger bones. He opened his hand, and the shadowy skeleton hand opened. Röntgen wondered if he could be hallucinating. In those days, some people believed that dreaming about or imagining seeing a skeleton was a premonition of one’s impending death. Röntgen was concerned that others might think him insane if he were to describe what he had seen, so he needed proof.

In the ensuing weeks, Röntgen made an intense study of the properties of x-rays. Three days before Christmas, he placed photographic film in a black paper package and had his wife, Bertha, place her hand on it while he exposed it with x-rays for fifteen minutes. The photograph showed the bones of Bertha Röntgen’s hand, with a ring on her finger. Röntgen sent a copy of the photograph along with an explanation to a friend, but it soon found its way into newspapers all over the world. Only four months after the public announcement, Thomas Edison’s company began marketing “complete outfits for x-ray work.” While some considered looking at skeletons while people were still using them revoltingly indecent, the medical usefulness of x-rays was immediately apparent. The first Nobel Prize in Physics ever awarded went to Röntgen in 1901 for his discovery of x-rays.

In spite of the obvious medical advantages, relatively few doctors used x-rays at first, but the public found them a source of entertainment. Edison built a fluoroscope for use at amusement parks. Looking through a hooded visor, spectators placed their hands between an x-ray tube and a fluorescent screen and watched their bones wiggle as they moved their hands. Casual exposure to x-rays continued into the 1950s with the use of fluoroscopes by shoe stores to see how well shoes fit.

The widespread use of medical x-rays was hampered by the lack of trained operators and proper equipment. This situation changed with World War I, when x-ray teams were trained and equipped by the hundreds. Marie Curie was a prime force in establishing such teams for the French and Belgian militaries. From this modest beginning, the various imaging techniques have evolved to provide the physician with “magic eyes” that can peer inside the body.

Bibliography

A.D.A.M. Medical Encyclopedia. "Imaging and Radiology." MedlinePlus, March 22, 2012.

Giger, Maryellen L., and Charles A. Pelizzari. “Advances in Tumor Imaging.” Scientific American 275, no. 3 (September, 1996): 110–12.

MedlinePlus. "Diagnostic Imaging." MedlinePlus, May 24, 2013.

Mould, Richard F. A Century of X Rays and Radioactivity in Medicine. Philadelphia: Institute of Physics, 1993.

OrthoInfo. "X-Rays, CT Scans, and MRIs." American Academy of Orthopaedic Surgeons, 2013.

Raichle, Marcus E. “Visualizing the Mind.” Scientific American 270, no. 4 (April, 1994): 58–64.

Ter-Pogossian, Michel M., Marcus E. Raichle, and Burton E. Sobel. “Positron-Emission Tomography.” Scientific American 243, no. 4 (October, 1980): 170–81.

Weissleder, Ralph, et al. Primer of Diagnostic Imaging. 4th ed. Philadelphia: Mosby/Elsevier, 2007.

In Ralph Ellison's Invisible Man, what does the Invisible Man mean when he says that Sybil sees him as an "entertainer?"

Late in the novel, the unnamed narrator, or the invisible man, meets Sybil at a bar. The narrator says of Sybil, "she was one of those who assumed that my lectures on the woman question were based upon a more intimate knowledge than the merely political and had indicated several times a willingness to know me better" (515). From the quote we know that Sybil has attended the invisible man's speeches on the woman question, a topic to which he was assigned as a sort of probation after inciting protests related to Tod Clifton's funeral. It is possible that part of her idea of the narrator being an "entertainer" stems from his successful reputation as a speaker. However, Sybil's thought that he is an "entertainer" also reveals that she hopes that he will perform stereotypical racial roles to fulfill her fantasies. 

Soon, the invisible man and Sybil begin a sexual affair. When they meet up, Sybil drinks excessively and begins to call the narrator "boo'ful," kind of a slurred version of "beautiful." Sybil seems to think of the invisible man as exotic and interesting because he is black. She fantasizes about "Warm ebony against pure snow," calling this contrast "poetic" (520). What Sybil desires is to be abused by the invisible man and to be sexually assaulted, or at least she wants the two of them to play the roles of victim (Sybil) and assailant (narrator). She calls the invisible man "you big black bruiser" and commands him to "knock [her] down" (522). The narrator understands that he is being asked to enact a stereotypical and offensive mock relationship between a black male aggressor and a white female victim. He is performing for Sybil, entertaining her darkest fantasies. The invisible man refers to this interaction with Sybil as "a farce" (523), recognizing that Sybil sees him as a toy to amuse herself with and their interaction as a game (523). 

What is a biopsy?

Indications and Procedures

Biopsy is one of the most common diagnostic tools in medicine. Illness or disease can be caused by biological agents (such as viruses, bacteria, fungi, and parasites), by physical agents (such as radiation, heat, extreme cold, and trauma), by genetic and metabolic abnormalities (such as diabetes), or by cancer, which is a new, abnormal growth commonly called a tumor. Often, however, the cause of an illness or disease may not be known. Nevertheless, the structural changes caused by the disease are characteristic enough so that the study of these alterations can give a clear picture of the nature and course of the disease. Diseases may primarily affect one organ at a time, such as hepatitis (the inflammation of the liver), or may involve many organ systems at once, as in Acquired immunodeficiency syndrome (AIDS).

The signs and symptoms of disease are not specific and are often shared by many conditions. For example, all diseases of the liver can result in jaundice, or yellowing of the skin, and abnormal blood tests. The clinician, who may be an expert in liver disease, may not be able to tell for certain whether the underlying liver condition is caused by a virus, by a toxic substance such as alcohol, or by both. A needle biopsy of the liver may then be obtained. The sample is examined by an expert surgical pathologist, and a specific diagnosis is rendered.

Similarly, a lump in the breast may be innocuous (benign) or cancerous (malignant). Only a biopsy of such a lesion can determine this conclusively. Such a biopsy can be obtained by fine needle aspiration, which is a simple procedure that can be performed in a clinic, or by excision in the operating room. A frozen section is then made for the purpose of rapid diagnosis and management.

Once a biopsy is obtained, it is placed in a special fixative, such as formalin. This solution will preserve—or fix—the internal structure of the tissue and its cells. Expert technicians in histology, called histotechnologists, will then embed the tissue in waxlike paraffin to obtain a “block.” The tissue block is then placed in a microtome, and extremely thin pieces (about 5 micrometers thick in width) are cut from it. The slices are placed on glass slides and stained with different dyes, the most common of which is hematoxylin and eosin (H & E), to delineate the cellular substructures. The slides are examined by a surgical pathologist, who renders a pathology report in which the gross and microscopic features are described, and a diagnosis is made. A differential diagnosis may also be made, in which other possible causes of disease that may give a similar histologic picture are discussed. In addition to the routine study described above, a much more extensive and expensive workup of the biopsy may be done, depending on the anticipated complexity of the condition and organ.

The study of a biopsy requires diligent preparation and staining of the tissue, which is the realm of histotechnologists. Staining refers to the application of artificial dyes to tissue sections and cells to facilitate their microscopic study. Certain tissues and cell parts have different chemical and biological affinities for dyes which, when properly applied, help demarcate and differentiate the properties of these cells. A huge battery of special stains exists that can be used to examine every aspect of cell function in both health and disease. For example, specific enzymes can be evaluated; this technique is called enzyme histochemistry.

Immunologic stains, which help evaluate the status of immune system cells, are expensive and extremely tedious, and their proper interpretation requires considerable expertise. Many antibodies are commercially available for such testing. When directed against specific antigenic cell markers, they form immune complexes that can be targeted with immunological stains. Such stains can then be evaluated by immunofluorescence or immunoperoxidase techniques. Both types employ as their principle of action the forming of complexes between antigens and antibodies and the staining of these complexes. Immunofluorescence staining techniques involve the use of special stains that cause the tissue to shine when it is viewed under a fluorescent microscope; such procedures are performed on frozen section tissues. With immunoperoxidase stains, fixed tissues are used, and the stains are permanent.

Tissue samples can also be studied with an electron microscope, in which electron beams greatly magnify subcellular structures. In this way, the alterations of specific cellular components such as cell membranes, mitochondria, and intracellular viruses can be visualized and analyzed. This ultrastructural study is especially valuable in needle biopsies of the kidneys, as well as in the study of certain unusual cancer cells.

Another highly sophisticated method used to evaluate tissue and cell function in a biopsy is the application of molecular genetics and molecular biopsy techniques. The
polymerase chain reaction (PCR) involves the splitting (splicing) of a specific section of genetic material in a cell and its amplification through a chemical chain reaction into innumerable folds, so that it can be visualized through a light microscope. This type of evaluation allows for the examination of specific microorganisms in a cell and can determine the presence of certain genetic markers of unusual diseases or cancer.

Another way to study the properties of cells is by examining their genetic makeup.
Karyotyping is a technique in which the actual chromosomes in a cell are photographed during mitotic divisions; the chromosomes appear as patterns of bands. Genetic abnormalities can be identified by the number of chromosomes and their appearance. This procedure is often used in the study of cancer cells. An even more sophisticated study of cellular genetic makeup is called gene rearrangement, in which the order of gene stacking is examined for specific markers of certain cancerous growths, especially of white blood cells. Other techniques that are used to evaluate cell functions and morphology are cellular imaging, in which the contours of cell membranes and surfaces are compared using computers, and the use of flow cytometers, in which cells are targeted immunologically and then counted. Both techniques are employed in cancer studies, and the second is also used for patients with abnormal immune systems, such as those with AIDS.

The aforementioned studies are expensive and available only at large medical centers and research institutes. The diagnostic workup in most hospitals, however, does not require the use of these sophisticated methods. Usually, routine H & E stains are applied. The Papanicolaou stain is commonly used with fine needle aspiration biopsies.

A department of pathology in a large medical center usually has one or more surgical pathologists, who are closely affiliated with the clinical and surgical departments and with their many branches and specialties. Interpreting biopsies obtained by any of the surgical or medical specialties is the most important duty of the surgical pathologist, and it requires great expertise and diligence. Because of the complexity of this task, specialized experts in pathology are becoming the norm. For example, a dermatopathologist is a surgical pathologist trained to interpret skin biopsies. Similarly, hematopathologists, neuropathologists, and nephropathologists are experts in the interpretation of blood-related, nerve- and brain-related, and kidney-related biopsies, respectively.

In incisional biopsies, only a portion of the lesion is sampled, and the procedure is strictly of a diagnostic nature. In excisional biopsy, the entire lesion is removed, usually with a rim of normal tissue, and therefore the procedure serves both a diagnostic and a therapeutic function. The decision whether to perform an incisional or an excisional biopsy depends primarily on the size and location of the lesion; the smaller the lesion, the more logical it is to remove it completely. It is preferable, however, to sample a deeply seated large tumor first because the type and extent of the excision varies considerably depending on the tumor type. For example, a small skin mole is usually excised completely, whereas a large soft tissue or bone tumor should be sampled.

Biopsies are also classified according to the instrument used to obtain them: cold knife versus cautery, needle, or endoscope. Of these the one usually least suitable for microscopic study is that obtained with a cautery, which uses a hot knife that burns, chars, and distorts tissue.

An endoscope is a tubelike fiber-optic instrument that is inserted into an orifice or small incision in order to view the contents of a body cavity. The instrument can be rigid or flexible and is equipped with a light source (usually a laser) and a small cutting tool at its tip to allow for the removal of small samples of tissue. Endoscopic biopsies are frequently used to obtain tissue and cell samples from the lungs and the airways, mainly to diagnose laryngeal and lung cancers; this procedure is usually done by a lung specialist. The endoscope is also used to sample lesions in the esophagus, stomach, intestines, and the rest of the intestinal tract, including the rectum. Such procedures are usually performed by a gastroenterologist, a specialist in the stomach and the gastrointestinal tract. Endoscopic biopsies of the urinary bladder and the prostate are done by urologists.

Needle biopsies
are commonly used to obtain samples from superficial or deep-seated lumps. A slender, cylindrical core of tissue, corresponding to the open diameter of the needle, is obtained. The needle biopsy is commonly used to obtain tissue samples from kidneys, bone, and the deep viscera such as the liver. The modified technique of aspiration cytology, commonly called fine needle aspiration, employs a fine-caliber needle (0.6 to 0.9 millimeter in open diameter) and is widely used to obtain cytologic and minute tissue samples, especially for lesions of the lymph
glands, breasts, thyroid gland, salivary glands, lungs, and prostate. Fine needle aspiration is often inexpensive, safe, quick, and, when performed and interpreted by experienced workers, quite accurate. Because of the ready availability and relative inexpense of the endoscopic and fine needle aspiration biopsy techniques, they have become popular; almost every part of the body is now within reach of one or another of these two techniques.

Frozen section biopsy
requires great expertise because this biopsy is usually a form of consultation done during surgery. A tissue sample is instantly frozen, sectioned, stained, and examined—all within about fifteen minutes—in order to render a specific diagnosis. The implications of this diagnosis are far reaching and will influence the surgical procedure and the long-term therapy and outcome for the patient. A frozen section report, for example,
may determine whether an organ such as a breast, lung, or kidney must be removed and whether long-term radiation therapy or chemotherapy will be administered; such would be the case if the diagnosis is read as malignant.

There are two indications, other than establishing a diagnosis, for performing a frozen section: determining the adequacy of the margins of surgical excision (for example, to remove a malignant tumor completely) and establishing whether the tissue obtained contains an ample diagnosable sample to carry out other specialized tissue studies.

Uses and Complications

The following examples illustrate the practical use of the various biopsy techniques.

An excisional biopsy is performed on a pigmented dark lesion on a sun-exposed surface of the body of a young man and is diagnosed as malignant melanoma, which is a tumor of the pigment-producing cells of the body. This diagnosis is confirmed through the use of specialized immunological stains employing specific antibodies against melanin. The pathologist also comments that surgical margins of excision of that tumor are safe and do not contain tumor, and that the tumor is only superficial in nature and does not show deep invasion into the tissue. These two points imply that the patient will probably have a complete cure.

A fine needle aspiration biopsy is applied on a lump on the breast of a young woman. The material obtained is spread on slides, stained with a Papanicolaou stain, and evaluated within hours of its removal. The lump is diagnosed as a fibroadenoma, which is a benign tumor that is completely innocuous and of no further consequence to the young patient.

An elderly patient has an endoscopic biopsy of a visualized mass in the colon, which proves to be cancer. The patient is taken to the operating room, and the colon is resected. A frozen section is performed on the margin on the surgical excision to make sure that it contains no tumor. The stains used in this example are the simple and routine H & E stains.

A liver biopsy is performed on a patient with jaundice (yellowing of the skin), and a diagnosis of viral hepatitis B is made. This diagnosis is made following the study of the liver biopsy by routine stains and by stains that use immunological antibodies against the viral antigen. This is a specific and highly accurate diagnostic study.

A lymph gland excisional biopsy is performed on a patient who feels lumps all over his body. The biopsy is examined with routine and special stains, immunological marker studies, and gene rearrangement. Such extensive studies are performed to make sure that his condition is completely benign and is not neoplastic—that is, that he does not have malignant lymphoma (cancer of lymph tissue).

The biopsy, in its varied forms and techniques, has become an essential component of quality medical care. The biopsy report is both a medical and a legal document. Tissue slides and blocks are often stored for many years, in some places indefinitely. Peer slide reviews and consultations are common and are used as gauges for quality control and management. There are some limitations with histologic diagnosis, which mainly revolve around recognizing a specialist’s own limitations and the need to seek a consultation by another expert pathologist as needed.

Bancroft, John D., and Marilyn Gamble, eds. Theory and Practice of Histological Techniques. 6th ed. New York: Churchill Livingstone/Elsevier, 2008.

Dubowitz, Victor, Caroline A. Sewry, and Anders Oldfors. Muscle Biopsy: A Practical Approach. Oxford: Saunders, 2013.

Fisher, Cyril, Elizabeth A. Montgomery, and Khin Thway. Biopsy Interpretation of Soft Tissue Tumors. Philadelphia: Wolters Kluwer/Lippincott, Williams and Wilkins, 2011.

Koss, Leopold G., Stanisław Woyke, and Włodzimierz Olszewski. Aspiration Biopsy: Cytologic Interpretation and Histologic Basis. 2d ed. New York: Igaku-Shoin, 1992.

Mills, Stacey E., et al., eds. Sternberg’s Diagnostic Surgical Pathology. 5th ed. 2 vols. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, 2010.

Rosai, Juan. Rosai and Ackerman’s Surgical Pathology. 9th ed. 2 vols. New York: Mosby, 2004.

Shah, Rajal B., and Ming Zhou. Prostate Biopsy Interpretation: An Illustrated Guide. New York: Springer-Verlag, 2012.

Sloan, John P. Biopsy Pathology of the Breast. 2d ed. New York: Oxford University Press, 2001.

Taxy, Jerome B., Aliya N. Husain, and Anthony G. Montag. Biopsy Interpretation: The Frozen Section. Philadelphia: Wolters Kluwer/Lippincott, Williams and Wilkins, 2010.

Yazdi, Hossein M., and Irving Dardick. Diagnostic Immunocytochemistry and Electron Microscopy: Guides to Clinical Aspiration Biopsy. New York: Igaku-Shoin, 1992.