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By M. Kor-Shach. Massachusetts College of Liberal Arts.

Patients with a history Blockade of dopamine metabolism makes more of cardiac arrhythmias or recent cardiac infarction dopamine available for stimulation of its receptors tegretol 100 mg on line. Selegiline buy tegretol 400mg on line, as monotherapy purchase 100mg tegretol overnight delivery, may be effective in the Also order tegretol 400mg, proteins ingested with meals may produce suffi- newly diagnosed patient with parkinsonism because its cient amounts of amino acids to compete effectively with pharmacological effect enhances the actions of endoge- levodopa transport both in the gastrointestinal tract and nous dopamine buy tegretol 200mg cheap. Levodopa therefore should be administered Selegiline is also used in conjunction with levodopa– at least 30 minutes before meals. Dopamine receptor agonists are considered by many It has also been proposed that selegiline may slow the clinicians as the first approach to therapy. They have a progression of the disease by reducing the formation of long duration of action and are less likely to cause dys- toxic free radicals produced during the metabolism of kinesias than levodopa. However, any neuroprotective ef- dopamine agonists is that they provide a means of di- fect of selegiline in parkinsonian patients remains to be rectly stimulating dopamine receptors and do not de- established. As Most of the adverse reactions to selegiline are re- monotherapy, the dopamine agonists are less effective lated to actions of increased levels of dopamine, as dis- than levodopa but are often used early in the disease to cussed earlier. When used as an nonselective MAO inhibitors used in the treatment of adjunct to levodopa in advanced stages, the dopamine depression, selegiline has little effect on MAO-A and receptor agonists may contribute to clinical improve- therefore generally does not cause the hypertension as- ment and reduce levodopa dosage needs. However, at doses higher than those are bromocriptine (Parlodel), pergolide (Permax), usually recommended, MAO-A may be inhibited, pramipexole (Mirapex), and ropinirole (Requip). Bromocriptine, an ergot derivative, is an agonist at the Selegiline should not be coadministered with tricyclic D2-receptors and a partial D1-antagonist. Pergolide, also antidepressants or selective serotonin uptake inhibitors an ergot derivative, is an agonist at both D1- and D2- because of the possibility of a severe adverse drug reac- receptor subtypes. Anticholinergic Drugs All four exert similar therapeutic effects and can produce the same adverse effects seen with levodopa. Before the introduction of levodopa, the belladonna The differences between the ergot derivatives and the alkaloids (e. The rationale for the use of COMT inhibitors is cholinergic agents with more selective central nervous analogous to that for carbidopa; that is, since COMT is system (CNS) effects. Trihexyphenidyl (Artane), ben- present in the periphery as well as in the CNS, inhibition ztropine mesylate (Cogentin), biperiden (Akineton), of peripheral COMT results in an increase in the and procyclidine (Kemadrin) are useful in most types of plasma half-life of levodopa, thereby making more drug parkinsonism. Additionally, com- The efficacy of anticholinergic drugs in parkinsonism pounds that block COMT in the CNS also prolong the is likely due to the ability to block muscarinic receptors brain concentration of levodopa. In the absence of the inhibitory action of The two COMT inhibitors in clinical use are tol- dopamine, the actions of the intrastriatal cholinergic in- capone (Tasmar) and entacapone (Comtan). They are terneurons are unopposed, yielding enhanced stimula- used in combination with levodopa–carbidopa. Blockade of these recep- tients with motor fluctuations, they increase the “on” tors reduces striatal activity. Adverse effects are similar to those observed with exert only modest antiparkinsonian actions and thus are levodopa–carbidopa alone. Tolcapone therapy can most commonly used during the early stages of the dis- cause fatal hepatotoxicity and so should be used only in ease or as an adjunct to levodopa therapy. Patients Of the drugs used for treating parkinsonism, the an- taking tolcapone require close monitoring of liver en- ticholinergics are the only class that can provide benefit zymes for signs of hepatic changes. This is because the blockade Nonpharmacological Approaches to the of dopamine receptors by the antipsychotics leads to in- Treatment of Parkinsonism creased activity of the striatal neurons. In general, due to their antimuscarinic effects in other systems surgical procedures are reserved for patients who are (e. Dyskinesias can be effectively cause it has anticholinergic properties, is used for mild controlled by ablation of the posteroventral portion of parkinsonism and with the elderly, who may not be able the globus pallidus. Brain stimulation appears to be a to tolerate the more potent anticholinergics, levodopa, promising technique. The grafting of early stages of parkinsonism or as an adjunct to levo- fetal substantia nigra tissue, which contains the dop- dopa therapy. Its mechanism of action in parkinsonism amine neurons, into the striatum of parkinsonian pa- is not clear, but amantadine may affect dopamine tients has been modestly successful. Additional sites of action may remain experimental, however, until the many practical include antagonism at muscarinic and N-methyl-D- problems and ethical issues associated with the use of aspartate (NMDA) receptors. The discovery of pluripotent nausea, dizziness, insomnia, confusion, hallucinations, stem cells is also being viewed as a possible way of de- ankle edema, and livedo reticularis.

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People of Jewish ancestry have a higher A spinal tap (lumbar puncture) is another procedure likelihood of getting leukemia buy generic tegretol 400 mg on line. In this leukemia has also been observed among persons with procedure buy tegretol 100mg, a small needle is inserted into the spinal cavi- Down syndrome and some other genetic abnormalities cheap tegretol 100mg otc. Similarly proven 400mg tegretol, the use of anticancer imaging (MRI) may be used to check whether the medications purchase tegretol 200 mg visa, immunosuppressants, and the antibiotic leukemic cells have invaded other areas of the body, such chloramphenicol also are considered risk factors for de- as the bones, chest, kidneys, abdomen, or brain. A patient may experience all or some of the mulates in the areas of cancer or infection, allowing following symptoms: them to be viewed with a special camera. These antioxidants, in patients 1206 GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 not undergoing chemotherapy, can be very helpful in (to help digest foods), hormones such as DHEA, mela- protecting the body against cancer. However, taken dur- tonin or phytoestrogens, rice bran, and mushroom ex- ing chemotherapy, these antioxidants protect the cancer tracts. It is best to check with a nutritional physician or cells from being killed by treatment. Patients Dietary guidelines should consult an experienced herbalist who will pre- scribe remedies to treat specific symptoms that are The following dietary changes may be helpful: caused by conventional cancer treatments. Daily consumption of the fol- • Increasing consumption of fresh fruits and vegetables. Homeopathy • Monitoring weight and eating adequate calories and There is conflicting evidence regarding the effec- protein. Therefore, patients should A naturopath or nutritional physician may recom- wait until after chemotherapy to try this relatively safe mend some of the following nutritional supplements to alternative treatment. Vitamins that are of particular Acupuncture benefit to cancer patients include beta-carotene, B- Acupuncture is the use of needles on the body to complex vitamins, (especially vitamin B 6, vitamins A, stimulate or direct the meridians (channels) of energy C, D, E and K. Acupuncture has not been shown to um, chromium, copper, iodine, molybdenum, germa- have any anticancer effects. Many of these vit- treatment for nausea, a common side effect of amins and minerals are strong antioxidants. Significant Other treatments adverse or toxic effects may occur at high dosage, Other therapies that may help the leukemia patient which is especially true for minerals. Guided imagery can apy or radiation therapy since these treatments kill the increase immune function and decrease pain and nausea. Allopathic treatment • Other nutritional supplements that may help fight can- cer and support the body include essential fatty acids There are two phases of treatment for leukemia. The (fish or flaxseed oil), flavonoids, pancreatic enzymes first phase is called induction therapy. The main aim of GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 1207 the treatment is to reduce the number of leukemic cells marrow is then frozen and saved. The marrow that leukemic cells are detected in blood tests and bone mar- was frozen is then thawed and given back to the patient row biopsies), the patient is said to be in remission. Substances that are routinely Chemotherapy is the use of drugs to kill cancer made by the immune system (such as growth factors, hor- cells. It is usually the treatment of choice and is used to mones, and disease-fighting proteins) are either syntheti- relieve symptoms and achieve long-term remission of the cally made in a laboratory or their effectiveness is boost- disease. This multiple drugs are used, is more efficient than using a treatment mode is also being investigated in clinical trials single drug for treatment. In 2002, scientists announced the discovery of a gene that triggers the death of leukemia cells. Identifica- Expected results tion of this gene can lead to better targeting of chemotherapy drugs (that involve a vitamin A deriva- Like all cancers, the prognosis for leukemia depends tive) for acute promyelocytic leukemia (APL). According to sta- advancement in leukemia treatment occurred in the same tistics, more than 60% of leukemia patients survive for at year. Further prognosis rate than acute lymphocytic leukemias (ALL) study was needed on both new discoveries, but they were and the chronic leukemias. In the last 15 to 20 years, the thought important to improving treatment of two forms five-year survival rate for patients with ALL has in- of leukemia. This is because via the blood stream and lymph vessels, surgery is not chemotherapeutic drugs are most effective against active- considered an option for treating leukemias. Due to the new combinations of anti- Radiation therapy, which involves the use of x rays cancer drugs being used, the survival rates among chil- or other high-energy rays to kill cancer cells and shrink dren with ALL have improved dramatically. For acute leukemias, cent of the children diagnosed with ALL now survive five the source of radiation is usually outside the body (exter- years or more, as compared to 50% in the late 1970s.

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Iron losses the body purchase tegretol 100mg, occurs mainly in the intestinal mu- from the body amount to about 1mg/day in cosa cheap tegretol 400 mg amex, liver order 400mg tegretol mastercard, bone marrow purchase 400 mg tegretol visa, red blood cells buy discount tegretol 100mg line, and men and up to 2mg/day in women due to plasma. Iron ab- 4500 Fe3+ ions and provides rapidly available sorption occurs mainly in the duodenum and stores of iron (ca. The absorption of iron lization from hemosiderin is much slower supplied by the diet usually amounts to about (250mg Fe in macrophages of the liver and 3 to 15% in healthy individuals, but can in- bone marrow). Hb-Fe and heme-Fe released crease to over 25% in individuals with iron from malformed erythroblasts (so-called in- deficiency (! A minimum daily iron in- efficient erythropoiesis) and hemolyzed red take of at least 10–20mg/day is therefore rec- blood cells bind to haptoglobin and ommended (women! Fe(II) supplied by gulfed by macrophages in the bone marrow or the diet (hemoglobin, myoglobin found chiefly in the liver and spleen, respectively, resulting in meat and fish) is absorbed relatively effi- in 97% iron recycling (! An iron deficiency inhibits Hb synthesis, With the aid of heme oxygenase, Fe in mucosal leading to hypochromic microcytic anemia: cells cleaves from heme and oxidizes to Fe(III). The Thetriferricformeitherremainsinthemucosa primary causes are: as a ferritin-Fe(III) complex and returns to the! If pH is important since it (a) increases the H+ the iron supply bypasses the intestinal tract (iron in- gradient that drives Fe2+ via DCT1 into the cell jection), the transferrin capacity can be exceeded and (b) frees dietary iron from complexes. The and the resulting quantities of free iron can induce absorption of iron into the bloodstream is iron poisoning. When an B12 vitamin (cobalamins) and folic acid are also iron deficiency exists, aconitase (an iron-regu- required for erythropoiesis (! Deficiencies lating protein) in the cytosol binds with fer- lead to hyperchromic anemia (decreased RCC, ritin-mRNA, thereby inhibiting mucosal fer- increased MCH). As a result, larger quantities intrinsicfactor(requiredforcobalaminresorp- of absorbed Fe(II) can enter the bloodstream. Because of the large apotransferrin, a protein responsible for iron stores available, decreased cobalamin absorp- transport in plasma (! Transferrin tion does not lead to symptoms of deficiency (=apotransferrin loaded with 2Fe(III)), is until many years later, whereas folic acid defi- 90 takenupbyendocytosisintoerythroblastsand ciency leads to symptoms within a few cells of the liver, placenta, etc. Iron intake and metabolism 1 Iron intake 2 Fe absorption Mucosal cells Normal Fe intake: Heme- (duodenum) 10–20 mg/day FeII 5–10 mg/day Heme Fe Fe absorption: Fe2+ FeIII Mucosal 3–15% of FR transferrin Fe intake HCI Fe Fe2+ Ferritin Fe Stomach + H FeIII Lyso- Liver some Cell FeIIIFeIII III turnover Fe Non-absorbed Fe in feces: Normally 85–97% of intake 3 Fe storage and Fe recycling Transferrin Fe Bone marrow Liver Systemic blood Ferritin Hemo-Heme Fe Ferritin Fe pexin Hemo- siderin Hapto- Hemo- globin Hb siderin Fe stores Erythrocytes Already in bone marrow Macrophages in spleen, liver and bone marrow (extravascular) B. Folic acid and vitamin B12 (cobalamins) NADP NADPH +H+ Folic acid Other organs Dihydrofolate 0. The sum of the concentrations of these parti- Viscosity (η) = 1/fluidity = shearing force cles yields a plasma osmolality of 290mOsm/ (τ)/shearing action (γ) [Pa·s]. The most abundant blood rises with increasing hematocrit and cationinplasmaisNa,andthemostabundant+ decreasing flow velocity. Although plasma major organelles and, therefore, are highly de- proteins carry a number of anionic net charges formable. Because of the low viscosity of their ("C),theirosmoticefficacyissmallerbecause contents, the liquid film-like characteristics of the number of particles, not the ionic valency, their membrane, and their high surface/ is the determining factor. The composition of in- twice as high as the viscosity of plasma (ηplasma terstitial fluid therefore differs significantly = 2 RU; water: 1 RU = 0. A completely different RBCs normally have no problem passing compositionisfoundinthecytosol,whereK+is through capillaries or pores in the splenic ves- the prevailing cation, and where phosphates, sels (see p. Blood viscosity is only slightly 378), and they provide a protein reserve in higher than plasma viscosity in arterioles times of protein deficiency. A critical increase in blood viscos- (apolipoproteins), hemoglobin (haptoglobin), itycanoccura)ifbloodflowbecomestooslug- iron (apotransferrin), cortisol (transcortin), gish and/or b) if the fluidity of red cells and cobalamins (transcobalamin). Most decreases due to hyperosmolality (resulting in plasma factors for coagulation and fibrinolysis crenation), cell inclusion, hemoglobin malfor- are also proteins. IgG, the most abundant immuno- dergo aggregation (rouleaux formation), in- globulin (7–15 g/L), can cross the placental creasing the blood viscosity tremendously (up barrier(maternofetaltransmission;"D). This can quickly lead to the cessa- Igconsistsoftwogroup-specific,heavyprotein tion of blood flow in small vessels ("p. Plasmaproteins Albumin Globulins 8 Blood α1 α2 β γ 60% 4% 8% 12% 16% 6 4 Plasma 2 Water 1 0 1 5 10 50 100 500 1000 Vessel inside diameter (µm) Electrophoretic protein fractions C. Ion composition of body fluids Interstitium Cytosol Cations Anions Cations Anions Cl– Proteins– + K+ Na – Inorganic HCO3 phosphate 2+ K+ Na+ HCO – Ca,Mg2+ Proteins,phosphates, 2+ 2+ 3 etc. The specific im- defenses linked with specific (acquired) im- mune system, with its T-killer cells (! C3), responds slowly: viruses, fungi, parasites and foreign (non-self) primary immune response or sensitization.

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B2) can be caused by an open chest process can be accelerated by pressing down wound or blunt chest trauma (e purchase tegretol 100 mg with amex. Since the tidal volume in- pinkindicatesthataresuscitationattemptwas creases due to hypoxia purchase tegretol 400mg with visa, high pressure levels (4kPa = successful buy generic tegretol 100mg. Mechanical intermittent impairment of cardiac filling and compression of the positivepressureventilation(IPPV)worksonthesame healthy contralateral lung tegretol 200 mg on line. Thistechniqueisusedwhentherespiratory pneumothorax consists of slow drainage of excess muscles are paralyzed due to disease tegretol 100 mg low price, anesthesia, pressure and measures to prevent further valvular etc. The exter- nal inspiratory and expiratory pathways are sepa- Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. Artificial respiration Fresh air Valves O2if needed Expiration Pump 1 Positive-pressure respiration 3 Mouth-to-mouth resuscitation Pump Negative pressure Normal pressure Pressure Inspiration Expiration Negative-pressure tank (iron lung) Gas flow Inspiration 2 Negative-pressure respiration Expiration B. Pneumothorax 2 Open pneumothorax Perforated tissue acts as valve 1 Normal Life-threatening 111 3 Valvular pneumothorax complication Despopoulos, Color Atlas of Physiology © 2003 Thieme All rights reserved. Lung volumes and lung–chest system returns to its intrinsic rest- capacities vary greatly according to age, height, ing position. The range of normal variation of VC, for ex- this is called the resting tidal volume (VT). Empirical formulas were there- spiration can be increased by another 3L or so fore developed to create normative values for better on forced (maximum) inspiration; this is interpretation of lung function tests. These reserve volumes are used during the standard deviation is given in parentheses. The The vital capacity (VC) is the maximum volume, V, of a gas (in L or m ; 1m3 3 = 1000L) volumeofairthatcanbemovedinandoutina canbeobtainedfromtheamount,M,ofthegas single breath. The total lung capacity is the where P is barometric pressure (PB) minus sum of VC and RV—normally 6 to 7L. All numerical values of these volumes apply under body STPD: Standard temperature pressure dry temperature–pressure saturation (BTPS) con- (273K, 101kPa, PH O2 = 0) ditions (see below). These lung volumes and H O-saturated2 capacities(exceptFRC,RV)canbemeasuredby (Tamb, P, PB H O2 at TAmb) routine spirometry. A) con- BTPS: Body temperature pressure-saturated sists usually of a water-filled tank with a bell- (310K, P, PB H O2 = 6. If VATPS is measured by spirometry at subject blows into the device (expiration), and room temperature (TAmb = 20#C; PH O2 sat = 2. Lung volumes and their measurement Water Residual volume Spirometer Functional residual capacity (FRC) Vital capacity Total lung capacity Paper feed Maximum inspiration +3 Inspiratory reserve volume +2 (ca. Dead Space, Residual Volume, Airway indirect techniques such as helium dilution (! Resistance The test subject is instructed to repeatedly in- The exchange of gases in the respiratory tract hale and exhale a known volume (VSp) of a occurs in the alveoli. The rest goes to dead tributesevenlyinthelungs(VL)andspirometer space (not involved in gas exchange) and is (! The the total helium volume does not change, the oral, nasal, and pharyngeal cavities plus the knowninitialheliumvolume(VSp! FHeO)isequal trachea and bronchi are jointly known as phys- to the final helium volume (VSp + V )L! VL iological dead space or conducting zone of the can be determined once FHex in the spirometer airways. The helium dilution method meas- to conduct incoming air to the alveoli and to ures gases in ventilated airways only. A)canbeusedtoesti- chamber and instructed to breathe through a mate the dead space. The product of each of the three volumes and its corresponding CO fraction gives the volume Such measurements can also be used to de- 2 of CO2 for each. The CO2 volume in the expired air termine airway resistance, RL, which is defined (VT! FECO2) equals the sum of the CO2 volumes in its as the driving pressure gradient between the two components, i. VT can be under normal conditions, especially during in- measuredusingaspirometer,andFECO2andFACO2can spiration when (a) the lungs become more ex- be measured using a Bunte glass burette or an in- frared absorption spectrometer.

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