By E. Norris. Saint Rose College.
Bone marrow—A spongy tissue located in the hol- Blood transfusions are performed in individuals that low centers of certain bones 20 mg atorlip-20 for sale, such as the skull and present with severe symptoms such as anemia and hip bones order atorlip-20 20mg with visa. A high risk associ- Globin—One of the component protein molecules ated with transfusions is iron overload generic 20mg atorlip-20 mastercard, which is fatal discount atorlip-20 20 mg. Normal adult hemoglobin Iron overload results due to inadequate amounts of serum has a pair each of alpha-globin and beta-globin transferring (a molecule that exchanges iron between molecules. Hemoglobin—Protein-iron compound in the Iron accumulation can lead to dysfunction of the heart, blood that carries oxygen to the cells and carries liver, and endocrine glands. Individuals receiving blood transfusions should keep Splenomegaly—Enlargement of the spleen. These include a serum ferritin Diagnosis test, liver biopsy, and radiological study performed by the Superconducting Quantum Interference Device Completing a family history, performing a complete (SQUID). This Bone abnormalities and masses or enlarged organs may method is the easiest and most affordable way of testing be recognized during physical examination. A liver ing to detect beta thalassemia can be done by completing biopsy is an invasive procedure that requires removal of an amniocentesis (obtaining a sample of amniotic fluid, a small piece of the liver. Lab results biopsy is very accurate in measuring the level of iron will vary depending on the type of beta thalassemia that stores in the body. Superconducting Quantum Interference Device, is also Normal hemoglobin results are 13–18 g/dl for males very accurate in measuring iron stores. Normal red blood cell counts highly specialized machine and few centers in the world are 4. In individuals with beta zero form of beta tha- lassemia major, there will be no HbA present in the Iron overload can be prevented with the use of iron blood. Chelating agents attract the excess iron and assist with the process of binding and detoxify- Symptoms of beta thalassemia minor may be similar ing this iron in the body. The drug deferoxamine (des- to those of sideroblastic anemia (a disorder characterized ferol) is one of the most widely used iron chelating by low levels of hemoglobin, fatigue, and weakness) and agents. Treatment is completed through nightly infu- sickle cell disease (a disease that changes red blood cell sions of deferoxamine by a pump or with daily intra- shape, rendering it incapable of functioning). Infusion by pump is used for the Symptoms of beta thalassemia major may be similar administration of high doses and low doses are given to those of hereditary spheocytic hemolytic anemia (pres- through injections. Beta thalassemia minima and minor usually require Individuals receiving blood transfusions should pay no treatment. Pregnant women that suffer from beta tha- close attention to iron intake in the diet. It is recom- 152 GALE ENCYCLOPEDIA OF GENETIC DISORDERS mended that children under age 10 keep dietary iron Resources intake at 10 mg/day or less. Individuals age 11 or older BOOKS should keep dietary iron intake at 18 mg/day or less. Dickey, and Cindy Smith Foods high in iron include: beef, beans, liver, pork, Greenberg. Children and Their Families: The continuum peanut butter, infant cereal, cream of wheat, prunes, of care. Thompson Increased amounts of iron in the body can cause a and Thompson Genetics in Medicine, Fifth Edition. Individuals with beta tha- PERIODICALS lassemia major are at risk for developing osteoporosis Angelucci, E. The New England intake of calcium and vitamin D can help increase the Journal of Medicine 343, (2000): 327-331. The Journal of The Bone marrow transplantation is another form of American Medical Association 285 (2001): 640-642. PO Box Adolescents may require counseling concerning the 8923, New Fairfield, CT 06812-8923. Gulli, MD port groups that focus on the time demand and lifestyle Tanya Bivens, BS changes of caring for a child diagnosed with beta tha- lassemia. Prognosis IBicuspid aortic valve Prognosis for beta thalassemia is good for individu- Definition als diagnosed early and those who receive proper treat- ment. Children with beta thalassemia major live 20-30 Bicuspid aortic valve is the most common malfor- years longer with treatment by blood transfusions and mation of the heart valves.
The development of chemistry made it pos- increasing body of knowledge concerned primarily with sible to isolate and synthesize chemically pure com- the poisonous aspects of drugs (the science of toxicol- pounds that would give reproducible biological results generic 20 mg atorlip-20 overnight delivery. Many other chemically pure active com- paralysis of sensory and motor nerves buy atorlip-20 20 mg with visa, followed eventu- pounds were soon obtained from crude drug prepara- ally by central nervous system depression and respira- tions atorlip-20 20mg discount, including emetine by Pelletier (1788–1844) from tory paralysis buy 20mg atorlip-20 with amex, precisely matches the known actions of ipecacuanha root; quinine by Carentou (1795–1877) the potent hemlock alkaloid, coniine. The use of drugs played an inti- an analysis of what was to become one of the basic con- mate part in the rites, religions, history, and knowledge of cerns of pharmacology, that is, the quantitative study of the South American Indians. It was soon realized that drug action is pro- was closely tied to religious thought, and Indian cultures duced along a continuum of effects, with low doses pro- treated their patients with a blend of religious rituals and ducing a less but essentially similar effect on organs and herbal remedies. It also was noted that the appear- various deities were as important as the appropriate ap- ance of toxic effects of drugs was frequently a function plication of poultices, decoctions, and infusions. Early drug practitioners, both in Europe and South Until the nineteenth century, the rapid development America, gathered herbs, plants, animals, and minerals of pharmacology as a distinct discipline was hindered by and often blended them into a variety of foul-smelling the lack of sophisticated chemical methodology and by and ill-flavored concoctions. The preparations were so distasteful led to an attempt to significant advances made through laboratory studies of improve on the “cosmetic” properties of these mixtures animal physiology accomplished by early investigators to ensure that patients would actually use them. Estonia, in the late 1840s by Rudolph Bucheim (1820– There has long been a tendency of some physicians 1879) (Fig. We can trace the history of this such as cathartics, alcohol, chloroform, anthelmintics, polypharmaceutical approach to Galen (A. Bucheim believed that “the investi- who was considered the greatest European physician gation of drugs. Galen believed that drugs had cer- for a chemist or pharmacist, who until now have been tain essential properties, such as warmth, coldness, dry- expected to do this. Unfortunately, he often formulated more was required to raise this discipline to the same general rules and laws before sufficient factual informa- prominent position occupied by other basic sciences; this tion was available to justify their formulations. They not only created new laboratories devoted to the laboratory investigation of drugs but also firmly established the new discipline through the training of future faculty, the writing of textbooks, and the founding of scientific journals and societies. In addition to of the biological effects that result from the administra- conducting his own outstanding research on the pharma- tion of chemical substances but rather the dual aims of cology of diuretics, emetics, cardiac glycosides, and so (1) providing an understanding of normal and abnormal forth, Schmiedeberg wrote an important medical text- human physiology and biochemistry through the appli- book and trained approximately 120 pupils from more cation of drugs as experimental tools and (2) applying to than 20 countries. Many of these new investigators either clinical medicine the information gained from funda- started or developed laboratories devoted to experimen- mental investigation and observation. These principles include chair of pharmacology first at the University of Michigan the study of the following: and then at Johns Hopkins University. Among his most important research accomplishments is an examination • The relationship between drug concentration of the chemistry and isolation of the active principles and biological response from the adrenal medulla (a monobenzyl derivative of • Drug action over time epinephrine) and the pancreas (crystallization of in- • Factors affecting absorption, distribution, bind- sulin). He also examined mushroom poisons, investigated ing, metabolism, and elimination of chemicals the chemotherapeutic actions of the arsenicals and anti- • Structure-activity relationships monials, conducted studies on tetanus toxin, and de- • Biological changes that result from repeated signed a model for an artificial kidney. In addition, Abel drug use: tolerance, addiction, adverse reactions, founded the Journal of Experimental Medicine, the altered rates of drug metabolism, and so forth Journal of Biological Chemistry, and the Journal of • Antagonism of the effects of one drug by an- Pharmacology and Experimental Therapeutics. His devo- other tion to pharmacological research, his enthusiasm for the • The process of drug interaction with cellular training of students in this new discipline, and his estab- macromolecules (receptors) to alter physiolog- lishment of journals and scientific societies proved criti- ical function (i. This expansion of infor- starting point for some of the most potent controls the mation has come about largely through the contribu- Food and Drug Administration (FDA) now exercises in tions of the biological sciences to medicine by a system- the drug field. This provision allowed the prescription atic approach to the understanding and treatment of drug to come under special control by requiring that it disease. The experimental method and technological carry the legend “Caution—to be used only by or on the advances are the foundations upon which modern med- prescription of a physician. Medicines were thought to pose cal manufacturer makes claims for its product beyond problems similar to those presented by foods. Efficacy those contained in an approved package insert, the was questioned in two respects: adulteration of active FDA may institute legal action against the deviations in medicines by addition of inert fillers and false claims advertising. Indeed, much of the development of the science New Drug Application (NDA) to the FDA for its ap- of pharmacy in the nineteenth century was standardiz- proval before the company was permitted to market a ing and improving prescription drugs. Efficacy (proof of effectiveness) became a re- A landmark in the control of drugs was the 1906 quirement in 1962 with the Kefauver-Harris drug Pure Food and Drug Act.
What niche will newer class III would not be expected with the estrogen replace- antiarrhythmic drugs occupy? Case Study Long QT Syndrome previously healthy 14-year-old athletic girl for developing polymorphic ventricular tachycardia Acomplained to her physician of a 6-day history (torsades de pointe) cheap atorlip-20 20 mg online, which may degenerate into of cough purchase atorlip-20 20mg without prescription, with 2 days of fever purchase 20 mg atorlip-20 visa, headache generic atorlip-20 20 mg line, and mild ventricular fibrillation and death. Several of her schoolmates had similar case, a thorough investigation of all her relatives symptoms and were treated with antibiotics. Her should be performed to search for family members physical examination revealed soft crackles at the with abnormal ECGs. A chest radiograph and ICD therapy that was instituted, the patient demonstrated mild interstitial haziness at the bases. A resource for pa- made, and she was given a prescription for 10 days tients with LQTS including a comprehensive list of of erythromycin. On the second day of therapy QT interval prolonging drugs can be found on the while at home, she suddenly lost consciousness internet at Cardiopulmonary resuscitation was initiated and then DC cardioversion was performed with a return to sinus rhythm. LQTS is caused by an abnormality in the function of specific ion channels responsible for myocardial repolarization. This may result from congenital mutations in the DNA en- coding the ion channels (inherited form) or may be acquired from pharmacological therapy or other ill- ness (increased intracerebral pressure, for example). After stopping the erythromycin, she was found to have an underlying long QT interval that was exac- erbated by the erythromycin. A detailed family his- tory confirmed the diagnosis when it was revealed that her mother had fainted on several occasions, and her first cousin (maternal) drowned while swimming in a lake 3 summers previously. Her physicians began -blocker therapy and recom- mended placing an implantable cardioverter– defibrillator. The alteration in repolarization nor- mally results from blockade of the rapid component of the delayed rectifier potassium current. In sus- ceptible patients, this may lead to a profound pro- longation of the QT interval and place them at risk. Gross DRUG LIST GENERIC NAME PAGE GENERIC NAME PAGE Atenolol 201 Nadolol 201 Diltiazem 203 Nitroglycerin 197 Isosorbide dinitrate 197 Pentaerythritol tetranitrate 197 Isosorbide mononitrate 197 Propranolol 201 Metoprolol 201 Verapamil 203 Angina pectoris is a clinical manifestation that re- and calcium entry blockers. An cial actions of these agents, it is important to be familiar acute anginal attack (secondary angina) is thought to with the major factors regulating the balance between occur because of an imbalance between myocardial myocardial oxygen supply and demand. This is gen- erally the result of severe coronary artery athero- THE THERAPEUTIC OBJECTIVES IN THE sclerosis. Angina pectoris (variant, primary angina) may USE OF ANTIANGINAL DRUGS also occur as a result of vasospasm of large epicardial coronary vessels or one of their major branches. A decrease in myocardial oxygen cardial ischemia by increasing myocardial oxygen sup- demand can be attained through use of the organic ni- ply or by decreasing myocardial oxygen demand or trates, calcium entry blockers, and -adrenoceptor block- both. Increases in myocardial oxygen supply are been shown to be effective in reducing the frequency, more difficult to achieve, especially when coronary blood severity, or both of primary or secondary angina. However, re- agents include the nitrates, -adrenoceptor antagonists, distribution of blood flow to the subendocardium of 196 17 Antianginal Drugs 197 the vasodilator action of the nitrates to be produced. The formation of nitrosothiols, and possibly free NO, has been proposed to stimulate intracellular solu- Oxygen Supply Oxygen Demand ble guanylate cyclase, which leads to an increase in in- tracellular cyclic guanosine monophosphate (GMP) Coronary blood flow Wall tension Aortic diastolic pressure Ventricular volume formation (Fig. The increase in GMP results in Endocardial–epicardial flow Radius or heart size vascular smooth muscle relaxation, possibly through in- Coronary collateral blood flow Systolic pressure hibition of calcium entry via L-type calcium channels, (afterload) decreased calcium release from the sarcoplasmic reticu- Large coronary artery diameter Diastolic pressure lum, or via an increase in calcium extrusion via a sar- (preload) colemmal Ca -adenosine triphosphatase (ATPase). Heart rate Contractility Absorption, Metabolism, and Excretion Nitroglycerin is a lipid-soluble substance that is rapidly ischemic areas has been documented in experimental an- absorbed across the sublingual or buccal mucosa. Its on- imals following nifedipine (Adalat, Procardia), diltiazem set of action occurs within 2 to 5 minutes, with maximal (Cardizem),verapamil (Calan), amlodipine (Norvasc), ni- effects observed at 3 to 10 minutes. Little residual activ- troglycerin (Nitrostat, Tridil, Nitro-Dur), or propranolol ity remains 20 to 30 minutes after sublingual adminis- (Inderal) administration. The plasma half-life of nitroglycerin, given ischemic areas also have been observed in experimental animals and humans after treatment with certain calcium entry blockers and organic nitrates.
A little were arrested for marijuana offenses that year purchase 20mg atorlip-20 with visa, with as more than a century later discount 20 mg atorlip-20 mastercard, the English Queen Elizabeth I many as 85% of these arrests for simple possession cheap 20mg atorlip-20 with mastercard, issued a decree commanding that landowners holding 60 rather than cultivation or commerce buy generic atorlip-20 20mg on-line. GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 1289 In a reversal of the state-by-state progression of crim- stituents of cannabis displayed antimicrobial action and inalizing marijuana that led to the 1937 Marijuana Trans- antibacterial effects in research studies. The components fer Tax Bill, there is a movement underway, state by state, CBC and d-9-tetrahydrocannabinol have been shown to to endorse the legalized use of medical marijuana. By destroy and inhibit the growth of streptococci and 1992, 35 states in the United States had endorsed referen- staphylococci bacteria. A growing body of scientific re- In 2002, the Dutch government announced that a search and many thousands of years of folk use support small trial would begin in the country to study the effects the importance of medical marijuana in treatment of a va- of medical marijuana on patients with multiple riety of illnesses, and the economic value of hemp in the sclerosis. After extending the number of participants in textile, paper, and cordage industries has a long history. The World Health Organization, in a 1998 study, stated that the risks from Cannabis contains chemical compounds known as cannabis use were unlikely to seriously compare to the cannabinoids. Different cannabinoids seem to exert dif- public health risks of the legal drugs, alcohol and tobac- ferent effects on the body after ingestion. And despite thousands of years of human consump- search indicates that these substances have potential tion, not one death has been directly attributed to therapeutic value for pain relief, control of nausea and cannabis use. Bakalar, JD, in a 1995 Journal of the American agent identified to date is 9-tetrahydrocannabinol, known Medical Association article, “Marijuana is also far less as THC. This chemical may constitute as much as 12% addictive and far less subject to abuse than many drugs of the active chemicals in the herb, and is said to be re- now used as muscle relaxants, hypnotics, and analgesics. Cannabis smoke carries even more tars and predominance of this mental lightness or “euphoria” de- other particulate matter than tobacco smoke. But the pends on the balance of other active ingredients and the amount smoked is much less, especially in medical use, freshness of the herb. THC degrades into a component and once marijuana is an openly recognized medicine, known as cannabinol, or CBN. Another chemical component, cannabidiol, known as CBD, has a sedative and mildly General use analgesic effect, and contributes to a somatic heaviness Every part of the cannabis plant, including buds, sometimes experienced by marijuana users. Despite persistent treatment of gonorrhea, angina pectoris (constricting legal restrictions and severe criminal penalties for illicit pain in the chest due to insufficient blood to the heart), use, marijuana continues to be widely used in the United and choking fits. It was also used for insomnia, neural- States, and throughout the world, both for its mood-alter- gia, rheumatism, gastrointestinal disorders, cholera, ing properties and its proven medicinal applications. The tetanus, epilepsy, strychnine poisoning, bronchitis, conflicting opinions on the safety and effectiveness of whooping cough, and asthma. Other phytotherapeutic cannabis in a climate of prohibition make any discussion (plant-based therapeutic) uses include treatment of ul- of its beneficial uses politically charged. Clinical studies have The United States federal government policy pro- demonstrated its effectiveness in relieving nausea and hibits physicians from prescribing marijuana, even for vomiting following chemotherapy treatments for seriously ill patients because of possible adverse effects, cancer. The herb has also been shown to reduce intra- and the disputed belief that cannabis is dangerously ad- ocular pressure in the eye by as much as 45%, a benefi- dictive. Cannabis has warned that physicians in any state who prescribed mari- proven anticonvulsive action, and may be helpful in juana could lose the privilege of writing prescriptions, be treating epilepsy. Other research has documented an in- excluded from Medicare and Medicaid reimbursement, vitro tumor inhibiting effect of THC. Marijuana also in- and even be prosecuted for a federal crime, according to creases appetite and reduces nausea and has been used a 1997 editorial in the New England Journal of Medi- with AIDS patients to counter weight loss and “wasting” cine. Several chemical con- medical use of marijuana and many other states have in- 1290 GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 troduced similar laws. The debate in the United States tolerance for most of the pharmacological effects. Some opponents ability to safely operate automobiles and machinery can believe that the movement to legalize marijuana for med- be impaired for up to eight hours after ingesting the herb. In early 2002, several published studies showed conflicting results about the effects of Preparations long-term chronic use of marijuana on memory and cog- Cannabis extracts, prepared for medicinal application, nitive function. Further research on the smoking, which quickly delivers the active ingredients to effects of marijuana on memory and how long those ef- the blood system.
As stated above purchase atorlip-20 20 mg overnight delivery, an intuitive navigation and interaction methodology is a crucial element for a well- fitted visualization framework purchase atorlip-20 20mg mastercard. By utilizing thePoincaré projection and the set of Möbius transformations (Coxeter discount 20 mg atorlip-20, 1957) a “fish-eye” fovea can be positioned on the HSOM grid allowing an intuitive interaction methodology cheap atorlip-20 20 mg with amex. Nodes within the fovea are displayed with high resolution, whereas the surrounding context is still visible in a coarser view. For further technical details of the HSOM see (Ritter, 1999; Ontrup & Ritter, 2001). It shows a navigation sequence where the focus was moved towards the highlighted region of interest. Note, that from the left to the right details in the target area get increasingly magnified, as the highlighted region occupies more and more display space. In contrast to standard zoom operations, the current surrounding context is not clipped, but remains gradually compressed at the periphery of the field of view. Since all operations are continuous, the focus can be positioned in a smooth and natural way. Browsing MEDLINE in Hyperbolic Space The following example presents a HSOM framework that combines the aspects of information retrieval, context enrichment and intuitive navigation into a single applica- tion. The following images show a two dimensional HSOM, where the nodes are arranged on a regular grid consisting of triangles similar to those in Figure 2. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Interactive Information Retrieval Towards Effective Knowledge Management 65 can be regarded as “containers” holding those documents for which the corresponding neuron is “firing” with the highest rate. We can then use visual attributes of these containers and the plane to reflect document properties and make context information explicit: • The container sizes reflect the number of documents situated in the corresponding neuron. Figure 3 shows a HSOM that was trained with approximately 25,000 abstracts from MEDLINE. The interface is split into two components: the graphical map depicted below and a user interface for formulating queries (not shown here). Subsequent to the query submission, the system highlights all nodes belonging to abstracts containing the word “brain” by elevating their corresponding nodes. Additionally the HSOM prototype vectors—which were autonomously organized by the system during a training phase—are used to generate a key word list which annotate and semantically describe the node with the highest hit rate. To this end, the words corresponding to the five largest components of the reference vector are selected. In the top left the most prominent MeSH terms are displayed, that is, 34 articles Figure 3. The user submitted the query string “brain” and the corresponding results are highlighted by the system. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. The user has moved the focus into the target area and can now inspect the context enriched data more closely. The map immediately shows that there are several clusters of brain-related articles in the right part of the map. By selecting single neurons with the mouse, the user can selectively retrieve key words of individual containers. As can be seen from the keyword distribution, all nodes share semantically related characteristics. The two leftmost labelled nodes do not contain key words like “brain” or “neuron”, but the labelling with “cord”, “spinal”, “eeg”, and “gamma”, respectively, indicates a close relation to the selected “brain-area”. The drill-down process to the document level combines the strengths of the graphical and the textual display: After zooming-in on a promising region, the titles of documents pertaining to a particular node can be displayed by a double mouse click. Note, that due to the ordering process of the SOM algorithm these documents are typically very similar to each other—and in the sense of the clustering hypothesis therefore might all provide an answer to the same query.