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| Skeletal Survey |
Skeletal surveyA skeletal survey is a series of X-rays of all the bones in the body, or at least the axial skeleton and the large cortical bones. A very common use is the diagnosis of multiple myeloma, where tumour deposits appear as "punched-out" lesions.
Category:Radiology
X-ray]
]
An X-ray or Röntgen ray is a form of electromagnetic radiation with a wavelength in the range of 10 nanometers to 100 picometers (corresponding to frequencies in the range 30 PHz to 3 EHz). X-rays are primarily used for diagnostic medical imaging and crystallography. X-rays are a form of ionizing radiation and as such can be dangerous.
Physics
X-rays with a wavelength approximately longer than 0.1 nm are called soft X-rays. At wavelengths shorter than this, they are called hard X-rays. Hard X-rays overlap the range of "long"-wavelength (lower energy) gamma rays, however the distinction between the two terms depends on the source of the radiation, not its wavelength: X-ray photons are generated by energetic electron processes, gamma rays by transitions within atomic nuclei.
The basic production of X-rays is by accelerating electrons in order to collide with a metal target (tungsten usually). Here the electrons suddenly decelerate upon colliding with the metal target and if enough energy is contained within the electron it is able to knock out an electron from the inner shell of the metal atom and as a result electrons from higher energy levels then fill up the vacancy and X-ray photons are emitted.
This causes the spectral line part of the wavelength distribution. There is also a continuum bremsstrahlung component given off by the electrons as they are scattered by the strong electric field near the high Z (proton number) nuclei.
Nowadays, for many applications, X-ray production is achieved by synchrotrons (see synchrotron light).
Detectors
Photographic plates
The detection of X-rays is based on various methods. The most commonly known method are a photographic plate and a fluorescent screen.
The X-ray photographic plate is frequently used in hospitals to produce images of the internal organs and bones of a patient. The part of the patient to be X-rayed is placed between the X-ray source and the photographic plate to produce what is a shadow of all the internal structure of that particular part of the body being X-rayed. The X-rays are blocked by dense tissues such as bone and pass through soft tissues. Where the X-rays strike the photographic plate it turns black when it is developed. So where the X-rays go through "soft" parts of the body like organs and skin the plate turns black. Contrast compounds containing barium or iodine can be injected in the artery of a particular organ. The contrast compounds strongly block the X-rays and hence the circulation of the organ can be more readily seen.
Another method of detecting X-rays is a fluorescent plate. In modern hospitals a special plastic sheet is used in place of the photographic plate. The plastic sheet is read by a scanning laser beam. The resultant image is then stored in a computer.
The plastic sheet can be used over and over again.
Geiger counters
Initially, most common detection methods were based on the ionisation of gases, as in the Geiger-Müller counter: a sealed cylinder with a polymer window contains a gas, and a wire, and a high voltage is applied between the cylinder (cathode) and the wire (anode). When an X-ray photon enters the cylinder, it ionizes the gas which becomes conducting, creating a current flow (a kind of flash); this peak of current is detected and is called a "count".
When the high voltage between anode and cathode is decreased, the detector is no longer saturated, and the height of the current peak is proportional to the energy of the photon; it is thus called a "proportional counter". Most of time, the cylinder is not sealed but is constantly fed with "fresh gas", is thus called a "flow counter". This proportionality property allows filtering the "interesting" peaks from the noise and other photons, but the resolution in energy is not enough to determine the energy spectrum; such a feature requires a diffracting crystal to first separate the different photons, the method is called wavelength dispersive X-ray spectroscopy (WDX or WDS).
Scintillators
Some materials such as NaI can "convert" an X photon to a visible photon; an electronic detector can be built by adding a photomultiplier. These detectors are called "scintillators", filmscreens or "scintillation counters". The main advantage of using these is that an adequate image can be obtained while subjecting the patient to a much lower dose of X-rays.
Direct semiconductor detectors
Since the 1970s, new semiconductor detectors have been developed (silicon or germanium doped with lithium, Si(Li) or Ge(Li)). X-ray photons are converted to electron-hole pairs in the semiconductor and are collected to detect the X-rays. When the temperature is low enough (the detector is cooled by Peltier effect or best by liquid nitrogen), it is possible to directly determine the X-ray energy spectrum; this method is called energy dispersive X-ray spectroscopy (EDX or EDS); it is often used in small X-ray fluorescence spectrometers. These detectors are sometimes called "solid detectors". Cadmium telluride (CdTe) and its alloy with zinc, cadmium zinc telluride detectors have have an increased sensitivity, which allows lower doses of X-rays to be used.
Silicon drift detectors (SDDs), produced by conventional semiconductor fabrication, now provide a cost-effective and high resolving radiation measurement. They replace conventional X-ray detectors, such as Si(Li)s, as they do not need to be cooled with liquid nitrogen.
Scintillator + Semiconductor detectors
With the advent of large semiconductor array detectors it has become possible to design detector systems using a scintillator screen to convert from X-rays to visible light which is then converted to electrical signals in an array detector.
Visibility to the Human Eye
It is commonly thought that X-rays are invisible to the human eye, and for almost all everyday uses of X-rays this may seem true; however, very strictly speaking, it is actually false. In special circumstances, X-rays are in fact visible to the "naked eye". An effect first discovered by Brandes in experimentation a short time after Röntgen's landmark 1895 paper; he reported, after dark adaptation and placing his eye close to an X-ray tube, seeing a faint "blue-gray" glow which seemed to originate within the eye itself.[http://www.orau.org/ptp/articlesstories/invisiblelight.htm] Upon hearing this, Röntgen reviewed his record books and found he in fact, also saw the effect. When placing an X-ray tube on the opposite side of a wooden door Röntgen saw the same blue glow seeming to emanate from the eye itself, but thought his observations were spurious due to the fact that he only saw the effect when he used one type of tube. Later he realized that the tube which
created the effect was the only one which produced X-rays powerful enough to make the glow plainly visible and the experiment was thereafter repeated readily. The fact that X-rays are actually faintly visible to the dark-adapted naked eye has largely been forgotten today is probably due to the lack of desire to repeat what we would now see as a recklessly dangerous and harmful experiment with ionizing radiation. It is not known what the exact mechanism in the eye is which produces the visibility and it could be due to either conventional detection (excitation of rhodopsin molecules in the retina), direct excitation of retinal nerve cells, or secondary detection via, for instance, X-ray induction of phosphorescence in the eyeball and then conventional retinal detection of the secondarily produced visible light.
Medical uses
phosphorescence
phosphorescence
Since Röntgen's discovery that X-rays can identify bony structures, X-rays have been developed for their use in medical imaging. Radiology is a specialized field of medicine that employs radiography and other techniques for diagnostic imaging. Indeed, this is probably the most common use of X-ray technology.
The use of X-rays are especially useful in the detection of pathology of the skeletal system, but are also useful for detecting some disease processes in soft tissue. Some notable examples are the very common chest X-ray, which can be used to identify lung diseases such as pneumonia, lung cancer or pulmonary edema, and the abdominal X-ray, which can detect ileus (blockage of the intestine), free air (from visceral perforations) and free fluid (in ascites). In some cases, the use of X-rays is debatable, such as gallstones (which are rarely radiopaque) or kidney stones (which are often visible, but not always). Also, Traditional plain X-rays pose very little use in the imaging of soft tissues such as the brain or muscle. Imaging alternatives for soft tissues are computed axial tomography (CAT or CT scanning), magnetic resonance imaging (MRI) or ultrasound.
X-rays are also used in "real-time" procedures such as angiography or contrast studies of the hollow organs (e.g. barium enema of the small or large intestine) using fluoroscopy. Angioplasty, medical interventions of the arterial system, rely heavily on X-ray-sensitive contrast to identify potentially treatable lesions.
Radiotherapy, a curative medical intervention, now used almost exclusively for cancer, employs higher energies of radiation.
History
Among the important early researchers in X-rays were Professor Ivan Pului, Sir William Crookes, Johann Wilhelm Hittorf, Eugen Goldstein, Heinrich Hertz, Philipp Lenard, Hermann von Helmholtz, Nikola Tesla, Thomas Edison, Charles Glover Barkla, Max von Laue, and Wilhelm Conrad Röntgen.
Wilhelm Conrad Röntgen
Physicist Johann Hittorf (1824 - 1914) observed tubes with energy rays extending from a negative electrode. These rays produced a fluorescence when they hit the glass walls of the tubes. In 1876 the effect was named "cathode rays" by Eugen Goldstein. Later, English physicist William Crookes investigated the effects of energy discharges on rare gases, and constructed what is called the Crookes tube. It is a glass vacuum cylinder, containing electrodes for discharges of a high voltage electric current. He found, when he placed unexposed photographic plates near the tube, that some of them were flawed by shadows, though he did not investigate this effect.
Tesla
In April 1887, Nikola Tesla began to investigate X-rays using high voltages and vacuum tubes of his own design, as well as Crookes tubes. From his technical publications, it is indicated that he invented and developed a special single-electrode X-ray tube, which differed from other X-ray tubes in having no target electrode. He stated these facts in his 1897 X-ray lecture before the New York Academy of Sciences.
The principle behind Tesla's device is nowadays called the Bremsstrahlung process, in which a high-energy secondary X-ray emission is produced when charged particles (such as electrons) pass through matter. By 1892, Tesla performed several such experiments, but he did not categorize the emissions as what were later called X-rays, instead generalizing the phenomenon as radiant energy. He did not publicly declare his findings nor did he make them widely known. His subsequent X-ray experimentation by vacuum high field emissions led him to alert the scientific community to the biological hazards associated with X-ray exposure.
Hertz
In 1892, Heinrich Hertz began experimenting and demonstrated that cathode rays could penetrate very thin metal foil (such as aluminium). Philipp Lenard, a student of Heinrich Hertz, further researched this effect. He developed a version of the cathode tube and studied the penetration by X-rays of various materials. Philipp Lenard, though, did not realize that he was producing X-rays. Hermann von Helmholtz formulated mathematical equations for X-rays. He postulated a dispersion theory before Röntgen made his discovery and announcement. It was formed on the basis of the electromagnetic theory of light (Wiedmann's Annalen, Vol. XLVIII). However, he did not work with actual X-rays.
Röntgen
Hermann von Helmholtz]
On November 8 1895, Wilhelm Conrad Röntgen, a German scientist, began observing and further documenting X-rays while experimenting with vacuum tubes. Röntgen, on December 28, 1895, wrote a preliminary report "On a new kind of ray: A preliminary communication". He submitted it to the Würzburg's Physical-Medical Society journal. This was the first formal and public recognition of the categorization of X-rays. Röntgen referred to the radiation as "X", to indicate that it was an unknown type of radiation. The name stuck, although (over Röntgen's great objections), many of his colleagues suggested calling them Röntgen rays. They are still referred to as such in many languages, where available see the list of titles for versions of this article in other languages. Röntgen received the first Nobel Prize in Physics for his discovery.
Röntgen was working on a primitive cathode ray generator that was projected through a glass vacuum tube. All of a sudden he noticed a faint green light against the wall. The odd thing he had noticed, was that the light from the cathode ray generator was traveling through a bunch of the materials in its way (paper,wood, and books). He then started to put various objects in front of the generator,and as he was doing this, he noticed that the outline of the bones from his hand were displayed on the wall. He then studied this phenomenon in seclusion.
Edison
In 1895, Thomas Edison investigated materials' ability to fluoresce when exposed to X-rays, and found that calcium tungstate was the most effective substance. Around March 1896, the fluoroscope he developed became the standard for medical X-ray examinations. Nevertheless, Edison dropped X-ray research around 1903 after the death of Clarence Madison Dally, one of his glassblowers. Dally had a habit of testing X-ray tubes on his hands, and acquired a cancer in them so tenacious that both arms were amputated in a futile attempt to save his life[http://www.ratical.org/radiation/KillingOurOwn/KOO6.html].
The 20th century and beyond
In 1906, physicist Charles Barkla discovered that X-rays could be scattered by gases, and that each element had a characteristic X-ray. He won the 1917 Nobel Prize in Physics for this discovery.
The use of X-rays for medical purposes (to develop into the field of radiation therapy) was pioneered by Major John Hall-Edwards in Birmingham, England. In 1908, he had to have his left arm amputated owing to the spread of X-ray dermatitis[http://www.birmingham.gov.uk/xray]. In the 1950s X-rays were first harnessed to produce an X-ray microscope.
X-ray microscope of, and occultation of the X-ray background by, the Moon.]]
In the 1980s an X-ray laser device was proposed as part of the Reagan administration's Strategic Defense Initiative, but the first and only test of the device (a sort of laser "blaster", or death ray, powered by a thermonuclear explosion) gave inconclusive results. For technical and political reasons, the overall project (including the X-ray laser) was de-funded (though was later revived by the second Bush administration as National Missile Defense using different technologies).
In the 1990s the Chandra X-Ray Observatory was launched, allowing the exploration of the very violent processes in the universe which produce X-Rays. Unlike visible light, which is a relatively stable view of the universe, the X-ray universe is unstable, it features stars being torn apart by black holes, galactic collisions, and novas, neutron stars that build up layers of plasma that then explode into space.
References
- [http://imagers.gsfc.nasa.gov/ems/xrays.html Nasa] Goddard Space Flight centre introduction to x-rays.
- Way Out There in the Blue: Reagan, Star Wars and the End of the Cold War, Frances Fitzgerald, Simon & Schuster (2001). ISBN 0743200233
See also
- X-ray crystallography
- X-ray astronomy
- X-ray machine
- X-ray microscopy
- Geiger counter
- N-ray
- X-ray vision
Category:X-rays
Category:Medical imaging
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Bone
, a typically recognized bone.]]
Bone, also called osseous tissue, (Latin: "os") is a type of hard endoskeletal connective tissue found in many vertebrate animals. Bones support body structures, protect internal organs, and (in conjunction with muscles) facilitate movement; are also involved with cell formation, calcium metabolism, and mineral storage. The bones of an animal are, collectively, known as the skeleton. Bone has a different composition than cartilage, and both are derived from mesoderm. In common parlance, cartilage can also be called "bone", certainly when referring to animals that only have cartilage as hard connective tissue, such as cartilaginous fish (Chondrichthyes) like sharks. True bone is present in bony fish (Osteichthyes) and all tetrapods.
There are several evolutionary alternatives to bone. These evolutionary solutions are not completely functionally analogous to bone.
- Exoskeletal protection is offered by shells, carapaces (consisting of calcium compounds or silica) and chitinous exoskelotons.
- A true endoskeleton (that is, protective tissue derived from mesoderm) is also present in Echinoderms. Porifera (sponges) possess simple endoskeletons that consist of calcareous or siliceous spicules and a spongin fiber network.
Bones and skeletons are studied in osteology. Bones can be prepared for study by several methods, such as maceration. Maceration is done by boiling fleshed bone with dish detergent and a little bleach until all large particles are off. The bones are then cleaned by hand, usually with a toothbrush and a degreaser.
Functions
Long bones can be connected to muscles via tendons. Bones connect at joints by ligaments. The interaction between bone and muscle is studied in biomechanics.
Post-mortem functions
Cut and polished bone from a variety of animals is sometimes used as material for jewelry and other crafts. Ground cattle bone is sometimes used as fertilizer. In the Stone Age bone was used to manufacture art, weapons, needles, etc.
Structure
art
art
Bone is a relatively hard and lightweight composite material, formed mostly of calcium phosphate in the chemical arrangement termed calcium hydroxyapatite. It has relatively high compressive strength but poor tensile strength. While bone is essentially brittle, it does have a degree of significant elasticity contributed by its organic components (chiefly collagen). Bone has an internal mesh-like structure, the density of which may vary at different points.
Bone can be either compact or cancellous (spongy). Cortical (outer layer) bone is compact; the two terms are often used interchangeably. Cortical bone makes up a large portion of skeletal mass; but, because of its density, it has a low surface area. Cancellous bone is trabecular (honeycomb structure), it has a relatively high surface area, but forms a smaller portion of the skeleton.
Bone can also be either woven or lamellar. Woven bone is put down rapidly during growth or repair. It is so called because its fibres are aligned at random, and as a result has low strength. In contrast lamellar bone has parallel fibres and is much stronger. Woven bone is often replaced by lamellar bone as growth continues.
Long bones are tubular in structure (e.g. the tibia). The central shaft of a long bone is called the diaphysis, and has a hollow middle—the medullar cavity filled with bone marrow. Surrounding the medullar cavity is a thin layer of cancellous bone that also contains marrow. The extremities of the bone are called the epiphyses and are mostly cancellous bone covered by a relatively thin cortical of compact bone. In children, the bones are filled with red marrow, which is gradually replaced with yellow marrow as the child ages.
Short bones (e.g. finger bones) have a similar structure to long bones, except that they have no medullar cavity.
Flat bones (e.g. the skull and ribs) consist of two layers of compact bone with a zone of cancellous bone sandwiched between them.
Irregular bones are bones which do not conform to any of the previous forms (e.g. vertebrae).
All bones consist of living cells embedded in a mineralised organic matrix that makes up the main bone material.
Cells
Bone Heads include osteoblasts, so called Bone Lining Cells, osteocytes and osteoclasts. Osteoblasts are typically viewed as bone forming cells. They are located near to the surface of bone and their functions are to make osteoid and manufacture hormones such as prostaglandin which act on bone itself. Osteoblasts are mononucleate. Active osteoblasts are situated on the surface of osteoid seams and communicate with each other via gap-junctions. They contain alkaline phosphatase—a chemical which has a role in the mineralisation of bone.
Bone Lining Cells (BLCs) share a common lineage with osteogenesis (bone forming) cells. They function as a barrier for certain ions, induced osteogenetic cells. They are flattened, mononucleate cells which line bone.
However, osteocytes do originate from osteoblasts which have migrated into and become trapped and surrounded by bone matrix which they themselves produce. The space which they occupy is known as a lacuna. Osteocytes have many processes which reach out to meet osteoblasts probably for the purposes of communication. Their functions include to varying degrees: formation of bone, matrix maintenance and calcium homeostasis. They possibly act as mechano-sensory receptors—regulating the bones' response to stress.
If osteoblasts can be described as bone forming cells, the osteoclasts can be described as bone destroying cells. Osteoclasts are large, multinucleated cells located on bone surfaces in what are called Howship's lacunae. These lacunae, or resorption pits, are left behind after the breakdown of bone and often present as scalloped surfaces. Because the osteoclasts are derived from a monocyte stem-cell lineage, they are equipped with engulfment strategies similar to circulating macrophages. Osteoclasts mature and/or migrate to discrete bone surfaces. Upon arrival active enzymes, such as acid phosphatase, are secreted against the mineral substrate. This process, called bone resorption, allows stored calcium to be released into systemic circulation and is an important process in regulating calcium balance. As bone formation actively fixes circulating calcium in its mineral form, resorption actively unfixes it thereby increasing circulating calcium levels. These processes occur in tandem at site-specific locations and are known as bone turnover, or remodeling. Osteoblasts and osteoclasts, coupled together via paracrine cell signalling, are referred to as bone remodeling units. The iteration of remodeling events at the cellular level is influential on shaping and sculpting the skeleton both during growth as well as after.
Matrix
The matrix comprises the other major constituent of bone. It has inorganic and organic parts. The inorganic is mainly crystalline mineral salts and calcium, which is present in the form of hydroxyapatite. The matrix is initially laid down as unmineralized osteoid (manufactured by osteoblasts). Mineralisation involves osteoblasts secreting vesicles containing alkaline phosphatase. This cleaves phosphate groups and acts as the foci for calcium and phosphate deposition. The vesicles then rupture and act as a centre for crystals to grow on.
The organic part of matrix is mainly Type I collagen. This is made intracellularly as tropocollagen and then exported. It then associates into fibrils. Also making up the organic part of matrix include various growth factors, the functions of which are not fully known. Other factors present include GAGs, osteocalcin, osteonectin, bone sialo protein and Cell Attachment Factor.
Formation
bone sialo protein
The formation of bone occurs by two methods: intramembranous and endochondral ossification. Intramembranous ossification mainly occurs during formation of the flat bones of the skull; the bone is formed from mesenchyme tissue. Endochondral ossification occurs in long bones, such as limbs; the bone is formed from cartilage.
Endochondral ossification begins with points in the cartilage called "primary ossification centers." They mostly appear during fetal development, though a few short bones begin their primary ossification after birth. They are responsible for the formation of the diaphyses of long bones, short bones and certain parts of irregular bones. Secondary ossification occurs after birth, and forms the epiphyses of long bones and the extremities of irregular and flat bones. The diaphyses and the epiphyses of long bones remain separated by a growing zone of cartilage (the metaphysis) until the child reaches skeletal maturity (18 to 25 years of age), whereupon the cartilage ossifies, fusing the two together (epiphyseal closure).
Marrow can be found in most any bone that holds cancellous tissue. In newborns, all such bones are filled exclusively with red marrow (or hemopoietic marrow), but as the child ages it is mostly replaced by yellow marrow (or fatty marrow). In adults, red marrow is mostly found in the flat bones of the skull, the ribs, the vertebrae and pelvic bones.
Remodeling is the process of resorption followed by replacement of bone with little change in shape and occurs throughout a person's life. Its purpose is the release of calcium and the repair of micro-damaged bones (from everyday stress). Repeated stress results in the bone thickening at the points of maximum stress. It has been hypothesized that this is a result of bone's piezoelectric properties, which cause bone to generate small electrical potentials under stress.
Bone pathologies
One of the most common bone illnesses is a bone fracture. Bones heal by natural processes, but untended and unsupported can lead to misgrown bone.
Other illnesses are for example osteoporosis and bone cancer (osteosarcoma). The joints can be affected by arthritis.
Terminology
:
There are also names for specific parts of long bones.
:
See also
- List of bones of the human skeleton
- Terms for anatomical location
External links
- [http://silver.neep.wisc.edu/~lakes/BoneElectr.html Review (including references) of piezoelectricity and bone remodelling]
Category:Anatomy
Category:Skeletal system
Category:Bone products
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simple:Bone
Multiple myeloma
Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease after Otto Kahler) is a presently incurable hematological malignancy of plasma cells, the cells of the immune system that produce antibodies. Its prognosis despite therapy is generally poor, and treatment may involve chemotherapy and stem cell transplant.
Signs and symptoms
Symptoms can include: malaise, bone pain, anemia, infections (due to decreased immunity) and fractures (due to breakdown of bone by malignant cells, as well as a tendency to brittle bones). Often, the diagnosis of multiple myeloma is made incidentally during routine blood tests for other conditions. The antibody that is produced in excess may cause specific medical problems, such as amyloid, acute renal failure and chronic renal failure, polyneuropathy and other disorders.
A mnemonic doctors use to remember the common tetrad of multiple myeloma is CRAB - C = Calcium (elevated), R =Renal failure, A = Anemia, B = Bone lesions.
Diagnosis
Investigations
The existence of unexplained anemia, kidney dysfunction, a high erythrocyte sedimentation rate (ESR) and a high serum protein (especially raised globulin) may suggest further testing. A doctor will then order protein electrophoresis of the blood and urine, on which a paraprotein (monoclonal protein, or M protein) band can be noticed. A type of paraprotein is the Bence Jones protein which is paraprotein composed of free light chains (see below). Quantitative measurements of the paraprotein are necessary to determine the severity of the disease. The paraprotein is a deviant immunoglobulin produced by the tumor clone. Very rarely, the myeloma is nonsecretory (not producing immunoglobulins).
In theory, myeloma can produce all classes of immunoglobulin, but IgD, IgM and IgE myeloma are very rare compared to IgG and IgA. In addition, light and heavy chains (the building blocks of antibodies) may be secreted in isolation: κ- or λ-light chains or any of the five types of heavy chains (α-, γ-, δ-, ε- or μ-heavy chains).
Additional findings are: a raised calcium (when myeloma cells are breaking down bone, releasing calcium into the bloodstream) and decreased renal function, which may be due to paraprotein deposition in the kidney).
Workup
The workup of suspected multiple myeloma includes a skeletal survey. This is a series of X-rays of the skull, axial skeleton and proximal long bones. Myeloma deposits appear as "lytic lesions" (with local disappearance of normal bone due to resorption), and on the skull X-ray as "punched-out lesions". A CT scan may be performed to measure the size of soft tissue plasmacytomas.
A bone marrow biopsy is usually performed to estimate the percentage of bone marrow occupied by plasma cells. This percentage is used in the diagnostic criteria for myeloma. Immunohistochemistry (staining particular cell types using antibodies against surface proteins) can detect plasma cells which express immunoglobulin in the cytoplasm but usually not on the surface; myeloma cells are typically CD56, CD138 positive and CD19 negative. Cytogenetics may also performed in myeloma for prognostic purposes.
Other useful laboratory tests include quantitative measurement of IgA, IgG, IgM and β2-microglobulin.
Criteria
New international critera, agreed in 2003, require the following:
- Plasma cells >10% on bone marrow biopsy or (in any quantity) in a biopsy from other tissues (plasmacytoma)
- A monoclonal protein in either serum (of >30 g/L) or urine
- Evidence of end-organ damage (related organ or tissue impairment, ROTI):
- Hypercalcemia
- Renal insufficiency
- Anemia
- Bone lesions
- Frequent severe infections (>2 a year)
- Amyloidosis of other organs
- Hyperviscosity syndrome
Some myelomas do not secrete any paraprotein. These are termed "non-secretory myeloma" with low or undetectable paraproteins on routine serum or urine protein electrophoresis. Measurement of serum free light chains may often be helpful to follow the disease burden in nonsecretory myeloma. It is rare compared to the secretory forms.
Related conditions are solitary plasmacytoma (a single tumor of plasma cells, typically treated with irradiation), plasma cell dyscrasia (where only the antibodies produce symptoms, e.g. amyloidosis) and monoclonal gammopathy of undetermined significance (MGUS). Most cases of myeloma probably start as MGUS.
Staging
International Staging System (ISS):
- Stage I: β2-microglobulin (β2M) < 3.5 mg/L, albumin >= 3.5 g/dL
- Stage II: β2M < 3.5 and albumin < 3.5; or β2M between 3.5 and 5.5
- Stage III: β2M > 5.5
Pathophysiology
Multiple myeloma develops in post-germinal center B lymphocytes.
A chromosomal translocation between the immunoglobulin heavy chain gene (on the fourteenth chromosome, locus 14q32) and a oncogene (often 11q13, 4p16.3, 6p21, 16q23 and 20q11) is frequently observed in patients with multiple myeloma. This mutation results in dysregulation of the oncogene which is thought to be important initiating event in the pathogenesis of myeloma. The result is proliferation of a plasma cell clone and genomic instability that leads to further mutations and translocations. The chromosome 14 abnormality is observed in about 50% of all cases of myeloma. Deletion of (parts of) the thirteenth chromosome is also observed in about 50% of cases.
Production of cytokines (especially IL-6) by the plasma cells causes much of their localised damage, such as osteoporosis, and creates a microenvironment in which the malignant cells thrive. Angiogenesis (the attraction of new blood vessels) is increased.
The produced antibodies are deposited in various organs, leading to renal failure, polyneuropathy and various other myeloma-associated symptoms.
Epidemiology
There are approximately 45,000 people in the United States living with multiple myeloma, and the American Cancer Society estimates that approximately 14,600 new cases of myeloma are diagnosed each year in the United States. It follows from here that the median prognosis is about three years.
Multiple myeloma is the second most prevalent blood cancer (10%) after non-Hodgkin's lymphoma. It represents approximately 1% of all cancers and 2% of all cancer deaths. Although the peak age of onset of multiple myeloma is 65 to 70 years of age, recent statistics indicate both increasing incidence and earlier age of onset.
Multiple myeloma affects slightly more men than women. African Americans and Native Pacific Islanders have the highest reported incidence of this disease and Asians the lowest. Results of a recent study found the incidence of myeloma to be 9.5 cases per 100,000 African Americans and 4.1 cases per 100,000 Caucasian Americans. Among African Americans, myeloma is one of the top 10 leading causes of cancer death.
Treatment
Treatment for multiple myeloma is focused on disease containment and suppression. Although allogeneic stem cell tranplant might cure the cancer, it is considered investigational given the high treatment related mortality of the procedure. In addition to direct treatment of the plasma cell proliferation, bisphosphonates (e.g. pamidronate) are routinely administered to prevent fractures and erythropoietin to treat anemia.
Initial therapy
Initial therapy is aimed at treating symptoms and reducing the burden of disease. A commonly used induction regimens include thalidomide with or without dexamethasone, and VAD (vincristine, doxorubicin (Adriamycin), and dexamethasone). Low-dose therapy with melphalan combined with prednisone can be used to palliate symptoms in patients who cannot tolerate aggressive therapy.
In patients who have good performance status, the next step in therapy is high-dose chemotherapy with melphalan with autologous stem cell transplantion. This can be given in tandem fashion, i.e. an autologous transplant followed by a second transplant.
Nonmyeloablative allogeneic stem cell transplant is being investigated as an alternative to autologous stem cell transplant.
Relapse
Frequently, myeloma progresses despite treatment. It has been observed that "treatment resistance" is a reversible effect, and that some new treatment modalities may re-sensitize the tumor to standard therapy. For patients with relapsed disease, bortezomib (or Velcade) is a recent addition to the therapeutic arsenal, especially as second line therapy. Bortezomib is a proteasome inhibitor. Finally, lenalidomide (or Revlimid), a less toxic thalidomide analog, is showing promise for treating myeloma. It awaits FDA approval.
Renal failure in multiple myeloma can be acute (reversible) or chronic (irreversible). Acute renal failure typically resolves when the calcium levels are brought under control. Treatment of chronic renal failure is dependent on the type of renal failure and may involve dialysis. Which type of renal failure a given patient has is difficult to determine at presentation.
Prognosis
Advanced age (age greater than 60), elevated lactate dehydrogenase, and decreased platelets are associated with a poorer prognosis. Cytogenetics may also be important for determining prognosis.
Patients
Some well-known patients include:
- Geraldine Ferraro
- Mel Stottlemyre
- Don Baylor
- Mel Goldstein
Deceased:
- Ann Landers
- Mark Lenard
See also
- Waldenström macroglobulinemia
- Multiple Myeloma Research Foundation
References
- Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med 2004;351:1860-73. PMID 15509819.
- International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749-57. PMID 12780789.
External links
- [http://www.myeloma.org International Myeloma Foundation]
- [http://www.multiplemyeloma.org Multiple Myeloma Research Foundation]
Category:Hematology
Category:Oncology
Greer CountyGreer County is a county located in the state of Oklahoma. As of 2000, the population is 6,061. Its county seat is Mangum6. From 1860 to 1896, the State of Texas claimed an area known as Greer County, Texas which included present-day Greer County along with neighboring areas.
Geography
According to the U.S. Census Bureau, the county has a total area of 1,667 km² (644 mi²). 1,656 km² (639 mi²) of it is land and 11 km² (4 mi²) of it is water. The total area is 0.67% water.
Adjacent counties
- Kiowa County (north)
- Jackson County (east)
- Harmon County (south)
- Beckham County (west)
Demographics
As of the census2 of 2000, there are 6,061 people, 2,237 households, and 1,442 families residing in the county. The population density is 4/km² (10/mi²). There are 2,788 housing units at an average density of 2/km² (4/mi²). The racial makeup of the county is 81.46% White, 8.78% Black or African American, 2.47% Native American, 0.26% Asian, 0.02% Pacific Islander, 3.99% from other races, and 3.02% from two or more races. 7.44% of the population are Hispanic or Latino of any race.
There are 2,237 households out of which 25.60% have children under the age of 18 living with them, 51.00% are married couples living together, 9.60% have a female householder with no husband present, and 35.50% are non-families. 33.40% of all households are made up of individuals and 19.80% have someone living alone who is 65 years of age or older. The average household size is 2.27 and the average family size is 2.87.
In the county, the population is spread out with 20.00% under the age of 18, 9.10% from 18 to 24, 28.40% from 25 to 44, 22.40% from 45 to 64, and 20.00% who are 65 years of age or older. The median age is 40 years. For every 100 females there are 123.80 males. For every 100 females age 18 and over, there are 129.60 males.
The median income for a household in the county is $25,793, and the median income for a family is $30,702. Males have a median income of $24,318 versus $18,641 for females. The per capita income for the county is $14,053. 19.60% of the population and 15.00% of families are below the poverty line. Out of the total population, 28.40% of those under the age of 18 and 14.80% of those 65 and older are living below the poverty line.
Cities and towns
- Granite
- Mangum
- Willow
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Category:Oklahoma counties
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