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THREE-CELL DIFFERENTIAL COUNT Instead of a manual differential count of WBCs proven 250 mg cefadroxil antibiotic interactions, many labs now rely on a three-cell differ- ential count that is automatically performed by newer instruments buy cefadroxil 250 mg with mastercard antibiotic pregnancy. White cells are sepa- rated on the basis of three sizes: small cells (mostly normal lymphocytes), middle cells T A B L E 5 – 2 N o r m a l C B C f o r S e l e c t e d A g e R a n g e s W B C C o u n t R B C C o u n t H e m o g l o b i n M C H M C H C M C V ( c e l l s / m m 3 ) ( 1 0 6 / µ L ) ( g / d L ) H e m a t o c r i t ( p g ) ( g / d L ) ( µ m 3 ) A g e [ S I : 1 0 9 / L ] [ S I : 1 0 1 2 / L ] [ S I : g / L ] ( % ) [ S I : p g ] [ S I : g / L ] * [ S I : f L ] R D W A d u l t? A b b r e v i a t i o n s : W B C = w h i t e b lo o d c e ll; M C H = m e a n c e ll h e m o g lo b i n ; M C H C = m e a n c e ll h e m o g lo b i n c o n c e n t r a t i o n ; M C V = m e a n c e ll v o lu m e ; R D W = r e d c e ll d i s t r i b u t i o n w i d t h. T A B L E 5 – 3 N o r m a l C B C f o r S e l e c t e d A g e R a n g e s P l a t e l e t L y m p h o c y t e s, N e u t r o p h i l s, N e u t r o p h i l s, C o u n t T o t a l B a n d S e g m e n t e d E o s i n o p h i l s B a s o p h i l s M o n o c y t e s ( 1 0 3 / µ L ) ( % W B C ( % W B C ( % W B C ( % W B C ( % W B C ( % W B C A g e [ S I : 1 0 9 / L ] c o u n t ) c o u n t ) c o u n t ) c o u n t ) c o u n t ) c o u n t ) A d u l t? If one of the three cell populations falls outside the reference range, the sample is made into a slide, and a microscopic differential count is performed. With the anticipated shortage of health care workers and the expense of manual counting, these types of determinations will be- come more widely used. As an example of the three-cell count, a patient with sepsis may have a large-cell count of 95% and a small-cell count of 5% with no middle cells. On manual examination of the 5 slide, there may be 70% segmented neutrophils and 25% stabs, for a total of 95%. THE “LEFT SHIFT” The degree of nuclear lobulation of PMNs is thought to give some indication of cell age. A predominance of immature cells with only one or two nuclear lobes separated by a thick chromatin band is called a “shift to the left. More than 20 five-lobed cells/100 WBCs suggest incip- ient megaloblastic anemia, and a six-lobed or seven-lobed poly is virtually diagnostic. In bands or stabs, the connection between the lobes of the nucleus is by a thick band; in segs, by a thin filament. A band is defined as a connecting strip wide enough to reveal two distinct margins with nu- clear material in between. For practical purposes, a left shift is present in the CBC when more than 10–12% bands are seen or when the total PMN count (segs plus bands) is greater than 80. Left Shift: Bacterial infection, toxemia, hemorrhage Right Shift: Liver disease, megaloblastic anemia, iron deficiency anemia RETICULOCYTE COUNT • Collection: Lavender top tube The reticulocyte count is not a part of the routine CBC. The count is used in the initial workup of anemia (especially unexplained) and in monitoring the effect of hematinic or ery- thropoietin therapy, monitoring the recovery from myelosuppression or monitoring engraft- ment following bone marrow transplant. Normal bone marrow responds to a decrease in erythrocytes (shown by a decreased hematocrit) with an increase in the production of reticulocytes. Lack of increase in a reticu- locyte count with an anemia suggests a chronic disease, a deficiency disease, marrow re- placement, or marrow failure. CBC DIFFERENTIAL DIAGNOSIS • See Tables 5–2 and 5–3 for normal age and sex-specific ranges. Calculated by 5 Hemoglobin (g / L) MCH = 6 RBC (10 / µL) Increased: Macrocytosis (megaloblastic anemias, high reticulocyte counts) Decreased: Microcytosis (iron deficiency, sideroblastic anemia, thalassemia) MCHC (Mean Cellular [Corpuscular] Hemoglobin Concentration) • 33–37 g/dL (SI:330–370 g/L) The average concentration of hemoglobin in a given volume of red cells. Calculated by the formula Hemoglobin (g / dL) MCHC = Hematocrit Increased: Very severe, prolonged dehydration; spherocytosis Decreased: Iron deficiency anemia, overhydration, thalassemia, sideroblastic anemia MCV (Mean Cell [Corpuscular] Volume) • 76–100 cu µm (SI: fL) The average volume of red blood cells. Increased: Sudden exercise, after trauma, bone fracture, after asphyxia, after surgery (espe- cially splenectomy), acute hemorrhage, polycythemia vera, primary thrombocytosis, 5 leukemias, after childbirth, carcinoma, cirrhosis, myeloproliferative disorders, iron deficiency Decreased: DIC, ITP, TTP, congenital disease, marrow suppressants (chemotherapy, alco- hol, radiation), burns, snake and insect bites, leukemias, aplastic anemias, hypersplenism, infectious mononucleosis, viral infections, cirrhosis, massive transfusions, eclampsia and preeclampsia, prosthetic heart valve, more than 30 different drugs (NSAIDs, cimetidine, as- pirins, thiazides, others) PMNs (Polymorphonuclear Neutrophils) (Neutrophils) • 40–76% • See also the “Left Shift” page 100. Severe exercise, last months of pregnancy, labor, surgery, new- borns, steroid therapy Pathologic. Bacterial infections, noninfective tissue damage (MI, pulmonary infarction, pancreatitis, crush injury, burn injury), metabolic disorders (eclampsia, DKA, uremia, acute gout), leukemias Decreased: Pancytopenia, aplastic anemia, PMN depression (a mild decrease is referred to as neutropenia, severe is called agranulocytosis), marrow damage (x-rays, poisoning with benzene or antitumor drugs), severe overwhelming infections (disseminated TB, sep- ticemia), acute malaria, severe osteomyelitis, infectious mononucleosis, atypical pneumo- nias, some viral infections, marrow obliteration (osteosclerosis, myelofibrosis, malignant infiltrate), drugs (more than 70, including chloramphenicol, phenylbutazone, chlorpro- mazine, quinine), B12 and folate deficiencies, hypoadrenalism, hypopituitarism, dialysis, fa- milial decrease, idiopathic causes RDW (Red Cell Distribution Width) • 11. Increased: Many anemias (iron deficiency, pernicious, folate deficiency, thalassemias), liver disease LYMPHOCYTE SUBSETS Specific monoclonal antibodies are used to identify specific T and B cells. Lymphocyte sub- sets (also called lymphocyte marker assays, or T- and B-cell assay) are useful in the diagno- sis of AIDS and various leukemias and lymphomas. The designation CD (“clusters of differentiation”) has largely replaced the older antibody designations (eg, Leu 3a or OKT3). Absolute CD4 count is used to initiate therapy with antiretrovirals or prophylaxis for PCP (see page 75). The CDC includes in the category of AIDS any patient with a CD4 count < 200 who is HIV-positive. General terms include poikilocytosis (irregular RBC shape such as sickle or burr) and anisocytosis (irregular RBC size such as microcytes and macrocytes).

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Not only is it suggest that they not be overcooked or boiled in too much effective buy cefadroxil 250mg with amex antibiotics vs antimicrobial, but at a cost of about $5 per patient discount cefadroxil 250mg on-line anabolic steroids, it proves water. Magnesium injections are ment recommended daily allowance (RDA) of magne- also used to treat acute asthma attacks. They think that it should be doubled to Magnesium preparations may be given as antacids about 600 or 700 mg daily for adults. They the use of dietary supplements containing magnesium to are also given as laxatives for the short-term relief of make up the difference. Magnesium hy- important in the relief or cure of the following conditions: droxide is used to treat patients who have been poisoned • Mitral valve prolapse: Magnesium deficiency may by mineral acids or arsenic. Magnesium may also be useful in treating attention-deficit hyperactivity disorder • Angina pectoris: Magnesium is thought to relax spastic (ADHD) and migraine headaches. Phosphate of magnesia is a staple • Premenstrual syndrome (PMS) and menstrual cramps: homeopathic remedy, called Magnesia phosphorica Some women report relief from the symptoms of PMS (Mag. Naturopaths emphasize the impor- Dietary supplements tance of proper food selection and preparation to obtain an adequate supply of nutrients in the diet. They maintain Naturopaths generally recommend supplemental that modern methods of agriculture promote overcrop- magnesium for people with high blood cholesterol, post- ping and soil depletion, which they believe reduces the menopausal women, women taking birth control pills, amount of magnesium (and other minerals) available diabetics, people who eat a lot of fast food or other high- from food grown in that soil. Many of wheat and rice, which discards the magnesium con- nutrition experts recommend supplements that contain a tained in the bran, wheat germ, or rice husks, also re- balanced ratio of calcium to magnesium, usually two duces the amount of magnesium in these foods. People who in- reasons naturopaths often recommend organic produce, crease their calcium intake should increase their dose of GALE ENCYCLOPEDIA OF ALTERNATIVE MEDICINE 2 1269 magnesium (and phosphate) as well, because they work together and complement each other. Magnesium can also be obtained from Electrolyte—A substance, such as potassium or herbal sources, such as red raspberries. Standard medical preparations Epsom salts—A preparation of magnesium sulfate, Magnesium hydroxide is a common over-the-counter used internally as a laxative or externally in com- antacid, available as either a tablet or liquid. Most antacid presses or warm baths to reduce swelling, inflam- tablets contain about 200 mg of magnesium hydroxide; mation, and itching from minor skin problems. Magnesium carbonate works as a cathartic or levels of magnesium in body fluids are too high. It laxative when combined with citric acid to produce mag- is almost always caused by a combination of low nesium citrate; it is often flavored with lemon or cherry to calcium levels and taking too much magnesium as make it more pleasant to swallow. Patients with hypermagne- the form of Epsom salts) is available over the counter, semia may have central nervous system depres- usually in half-pound or pound boxes. The symptoms of hypomagnesemia in- Magnesium for intravenous dosage is prepared as a sul- clude heart arrhythmias, muscle tremors or twitch- fate in a 50% solution. In general, intravenous administration es, seizures, hyperactive reflexes, and psychiatric of magnesium is reserved for patients with such serious symp- symptoms. Magne- ganic elements in human nutrition, distinguished sium sulfate can also be given by intramuscular injection. In addition, these preparations should not be used rou- Tetany—A disorder of the nervous system charac- tinely to relieve constipation, as the patient may become de- terized by muscle cramps, spasms of the arms and hydrated, lose calcium from the body, or develop a depen- legs, and numbness of the extremities. Antacids containing magnesium should be tom of an abnormality in calcium metabolism. Magnesium trolyte imbalance; and abdominal cramps when taken as sulfate, if given intravenously, is incompatible with cal- a laxative. Milk of magnesia occasionally produces nau- cium gluceptate, clindamycin, dobutamine, polymyxin B sea or diarrhea. Institute of Medicine (1997) Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. The Vedas, or ancient Hindu scriptures, also men- tion the treatment of diseases with lodestones. The word “lodestone” or leading stone, came from the use of these stones as compasses. The word “magnet” probably stems from the Greek Magnes lithos, or “stone from Magne- Magnetic therapy sia,” a region of Greece rich in magnetic stones. Gilbert allegedly used magnets to re- lieve the arthritic pains of Queen Elizabeth I. Contempo- Magnetic therapy dates as far back as the ancient rary American interest in magnetic therapy began in the Egyptians. Magnets have long been believed to have 1990s, as several professional golfers and football play- healing powers associated with muscle pain and stiff- ers offered testimony that the devices seemed to cure ness. The an- Many centuries ago, the earth was surrounded by a cient Chinese medical text known as The Yellow Emper- much stronger magnetic field than it is today.

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About 90% of patients with ventricular prema- Procainamide ture contractions and 80% of patients with ventricular tachycardia respond to procainamide administration generic 250 mg cefadroxil with visa antimicrobial resistance 5 year strategy. Procainamide (Pronestyl purchase 250mg cefadroxil with mastercard treatment for dogs going blind, Procan SR) is a derivative of Although the spectrum of action and electrophysio- the local anesthetic agent procaine. Procainamide has a logical effects of quinidine and procainamide are simi- longer half-life, does not cause CNS toxicity at thera- lar, the relatively short duration of action of pro- peutic plasma concentrations, and is effective orally. Adverse Effects Electrophysiological Actions Acute cardiovascular reactions to procainamide admin- istration include hypotension, A-V block, intraventricu- Table 16. The drug dosage must be reduced or even stopped if severe depression of conduction (severe pro- Hemodynamic Effects longation of the QRS interval) or repolarization (severe prolongation of the QT interval) occurs. The hemodynamic alterations produced by pro- cainamide are similar to those of quinidine but are not Long-term drug use leads to increased antinuclear as intense. Alterations in circulatory dynamics vary ac- antibody titers in more than 80% of patients; more than cording to the cardiovascular state of the individual. The symptoms may disappear within a few days nounced after intramuscular administration and seldom of cessation of procainamide therapy, although the tests occur after oral administration. Pharmacokinetics Procainamide, unlike procaine, has little potential to The pharmacokinetic characteristics of procainamide: produce CNS toxicity. Oral bioavailability 75–95% Onset of action 5–10 minutes Contraindications Peak response 60–90 minutes Duration of action 4–10 hours Contraindications to procainamide are similar to those Plasma half-life 2. Because of its effects on A-V nodal and Primary route of Hepatic; active metabolite His-Purkinje conduction, procainamide should be ad- metabolism ministered with caution to patients with second-degree Primary route of 50–60% renal (unchanged) A-V block and bundle branch block. Procainamide excretion should not be administered to patients who have shown Therapeutic serum 4–10 g /mL procaine or procainamide hypersensitivity and should concentration be used with caution in patients with bronchial asthma. Prolonged administration should be accompanied by Clinical Uses hematological studies, since agranulocytosis may occur. Procainamide is an effective antiarrhythmic agent when Drug Interactions given in sufficient doses at relatively short (3–4 hours) dosage intervals. Procainamide is useful in the treatment The inherent anticholinergic properties of procainamide of premature atrial contractions, paroxysmal atrial tachy- may interfere with the therapeutic effect of cholinergic cardia, and atrial fibrillation of recent onset. Patients receiving cimetidine and procainamide is only moderately effective in converting atrial flutter or may exhibit signs of procainamide toxicity, as cimetidine chronic atrial fibrillation to sinus rhythm, although it has inhibits the metabolism of procainamide. Simultaneous 174 III DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM use of alcohol will increase the hepatic clearance of pro- transmission therefore will be determined by the sum of cainamide. Procainamide may enhance or prolong the its direct depression and indirect facilitation of trans- neuromuscular blocking activity of the aminoglycosides mission. The simultaneous administration of quinidine or amio- His-Purkinje System and Ventricular Muscle darone may increase the plasma concentration of pro- Disopyramide administration reduces membrane cainamide. Action potentials are prolonged after Disopyramide (Norpace) can suppress atrial and ven- disopyramide administration, and this results in an in- tricular arrhythmias and is longer acting than other crease in the ERPs of His-Purkinje and ventricular drugs in its class. Unlike procainamide and quinidine, disopyramide does not produce postrepolarization re- Electrophysiological Actions fractoriness. The effect of disopyramide on conduction velocity The effects of disopyramide on the myocardium and depends on extracellular K concentrations. Electrocardiographic Changes Sinoatrial Node The direct depressant actions of disopyramide on The electrocardiographic changes observed after the sinoatrial node are antagonized by its anticholiner- disopyramide administration are identical to those seen gic properties, so that at therapeutic plasma concentra- with quinidine and procainamide. Both the anticholinergic and direct de- Hemodynamic Effects pressant actions of disopyramide on sinus automaticity appear to be greater than those of quinidine. At usual Disopyramide reduces membrane responsiveness in therapeutic doses, depression of myocardial function is atrial muscle and the amplitude of the action potential. Action po- Despite the decrease in cardiac output produced by tential duration in atrial muscle fibers is prolonged by disopyramide, blood pressure is well maintained by a disopyramide administration. Postrepolarization refractoriness does not occur administration can reverse the myocardial depression. Pharmacokinetics Abnormal atrial automaticity may be abolished at disopyramide plasma concentrations that fail to alter ei- The salient pharmacokinetic features of disopyramide: ther conduction velocity or refractoriness. Disopyramide increases atrial refractoriness in patients pretreated with Oral bioavailability 87–95% atropine, suggesting that the primary action of disopyra- Onset of action 30 minutes–3. Its anticholinergic actions, however, produce an in- excretion 15% biliary crease in conduction velocity and a decrease in the Therapeutic serum 1–5 g /mL ERP. The net effect of disopyramide on A-V nodal concentration 16 Antiarrhythmic Drugs 175 Clinical Uses verapamil, which may adversely affect atrioventricular conduction. The indications for use of disopyramide are similar to those for quinidine, except that it is not approved for Drug Interactions use in the prophylaxis of atrial flutter or atrial fibrilla- tion after DC conversion.

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Once an ontology for a certain domain is available cefadroxil 250mg antibiotics for acne redness, it can be used as a template to transfer the therein contained explicit knowledge to corresponding terms of free text from that domain buy cefadroxil 250mg free shipping antibiotics for cellulitis. For example, the term “blepharitis” is defined as “inflammation of the eyelids” in the UMLS. However with knowledge from the UMLS, these documents could be marked as relevant to the query. However, the tagging of free text with matching counterparts from an ontology is either a cost intensive human labor or requires advanced natural language processing methods. We shall see below, how computational approaches could address the problem of adding semantics to free narrative text. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Interactive Information Retrieval Towards Effective Knowledge Management 57 Biomedical Publications For most of the time in human history, the majority of knowledge acquired by mankind was passed on by the means of the written word. It is a natural scientific process to formulate new insights and findings and pass them to the community by publishing. It is not only expanding at growing speed, but also increasing in diversification, resulting in highly specialized domains of expertise. National Library of Medicine (NLM) has become the standard bibliographic database covering the fields of medicine, nursing, veterinary medicine, dentistry, pharmacology, the healthcare system, and the preclinical sciences. The majority of publications in MEDLINE are regular journals and a small number of newspapers and magazines. The database is updated on a regular daily basis from Tuesdays to Saturdays and on an irregular basis in November and December. At the time of this writing, MEDLINE contains approximately 12 million references to articles from over 37,000 international journals dating back to 1966. In 1980 there were about 100,000 articles added to the database, and in 2002 the number increased to over 470,000 newly added entries. That means, currently over 50 new biomedical articles are published on an hourly basis. Clearly, no human is able to digest one scientific article per minute 24 hours a day, seven days a week. But the access to the knowledge within is lively important nonetheless: “The race to a new gene or drug is now increasingly dependent on how quickly a scientist can keep track of the voluminous information online to capture the relevant picture … hidden within the latest research articles” (Ng & Wong, 1999). Not surprisingly, a whole discipline has emerged which covers the field of “information retrieval” from unstructured document collections, which takes us to the next section. Computational Approaches to Handle Text Databases The area of information retrieval (IR) is as old as man uses libraries to store and retrieve books. With the advent of the World Wide Web, the desire to find relevant and useful information grew to a public need. Consequently, the difficulties to localize the desired information “have attracted renewed interest in IR and its techniques as promising solutions. As a result, almost overnight, IR has gained a place with other technologies at the center of the stage” (Baeza-Yates & Ribeiro-Neto, 1999). Several approaches have shown that advanced information retrieval techniques can be used to significantly alleviate the cumbersome literature research and sometimes even discover previously unknown knowledge (Mack & Hehenberger, 2002). Swanson and Smalheiser (1997) for example designed the ARROWSMITH system which analyses journal titles on a keyword level to detect hidden links between literature from different specialized areas of research. Other approaches utilize MeSH headings (Srinivasan & Copyright © 2005, Idea Group Inc. Copying or distributing in print or electronic forms without written permission of Idea Group Inc. Rzhetsky, Iossifov, Koike, Krauthammer, Kra, Morris, Yu, Duboue, Weng, Wilbur, Hatzivassiloglou, and Friedman (2004) have recently proposed an integrated system which visualizes molecular interaction pathways and therefore has the ability to make published knowledge literally visible. In the following sections we go into more detail and look how computational methods can deal with text. Representing Text The most common way to represent text data in numerical form such that it can be further processed by computational means is the so-called “bag of words” or “vector space” model. To this end a standard practice composed of two complementary steps has emerged (Baeza-Yates & Ribeiro-Neto, 1999): 1. Indexing: Each document is represented by a high-dimensional feature vector in which each component corresponds to a term from a dictionary and holds the occurrence count of that term in the document. The dictionary is compiled from all documents in the database and contains all unique words appearing throughout the collection.

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These injections rely on diffusion of the delivered agent to reach brain tissue away from the injected site buy 250 mg cefadroxil with visa antibiotics z pack and alcohol. Unfortunately buy 250mg cefadroxil free shipping antibiotic resistance virtual lab, multiple studies demonstrated that diffusion of agents in the brain is extremely limited, particularly with high molecular weight or polar molecules. A more feasible approach is to use fewer catheters and increase the volume of diffusion through each catheter using CED. CED uses sustained intracerebral infusion to induce a convective interstitial fluid current that has the potential to homogeneously distribute even large molecules great distances within the brain by displacing interstitial fluid. Although a few studies have been conducted using CED in humans,142 no data are available on the actual distribution of agents delivered in the human brain via this method. Data recently submitted for publication demonstrate distribution of at least 10% of the injected concentration of a macromolecule within a nearly spherical radius over 4 cm from the catheter tip throughout the gray and white matter sur- rounding a tumor resection cavity (D. In addition to this encouraging data on distribution of agents in the human brain using CED, two clinical trials demonstrated the efficacy of CED in treating human brain tumor patients. Although these results are encouraging, several limiting factors remain as obsta- cles to the use of CED in the treatment of HGG patients. First, although a distribution of agent 4 cm from the catheter tip is encouraging, the technique still requires infusion via multiple catheters and careful optimization and planning to deliver therapeutic agent to the region surrounding a tumor or its resection cavity. Second, tumors clearly alter the fluid dynamics in the brain and the effect of this alteration on CED is poorly understood. Despite these limitations, further studies aimed at optimizing catheter design and infusion parameters should identify modifications capable of effectively addressing these issues now that the potential utility of this approach has been established in humans. A targeted toxin is attached to a receptor ligand; an immunotoxin consists of a toxin attached to an antibody that recognizes a receptor. In both cases, receptors selected for targeting are over-expressed on tumor cells (for simplicity, this chapter will use the term “targeted toxin” in reference to both moieties). Targeted toxins allow targeted delivery of potent toxins to tumors with relative sparing of normal tis- sue. Such toxins have at least two important advantages over most chemotherapeutic agents: (1) they are far more potent, while most © 2005 by CRC Press LLC chemotherapies require >104 molecules to kill a single tumor cell, many toxins require only one,133 and (2) they are active against hypoxic and nondividing cells, making them potentially effective against tumors that are resistant to chemotherapy and radiation. Critical to the success of targeted toxin therapy is the identifi- cation of a receptor that is ubiquitously highly expressed on the tumor but not on surrounding tissue. Clinical trials using targeted toxin therapy have targeted interleukin-2 receptors in hemato- logic malignancies146 and interleukin-13 receptors in squamous cell carcinomas. A simultaneous examination of GBM samples for EGFR gene amplification, mRNA, and protein found approximately one-third had gene amplification, all had mRNA, and 85% had detectable EGFR protein151 (McLendon et al. By contrast, EGFR was found in only very low levels in surrounding brain — a cir- cumstance that lends it to targeted toxin treatment with minimal unwanted toxicity. It is a recombinant chimeric protein composed of TGF-α and a genetically engineered form of the pseudomonas exotoxin PE-38. Encouraging results of a Phase I clinical trial examining treatment of patients with recurrent HGGs using CED of TP-38 have recently been submitted for publication. Targeted toxins for interleukin-4 and interleukin-13 receptors showed therapeutic efficacy against HGGs. Even more importantly, a variety of scientific advances led to the development and rapid translation to clinical trials of many novel forms of cancer therapy, broadly increasing the landscape of potential therapies far beyond the traditional modes of surgery, chemotherapy, and radiation. Although we have not yet discovered the combination of novel therapy and better understanding of underlying tumor mechanisms that will lead to an efficacious new © 2005 by CRC Press LLC treatment of HGGs, many promising new therapies are on the horizon. In this environment of rapid new discovery, it remains of utmost importance that neurosur- geons are involved in and informed of the development of these exciting new therapies that may soon allow us to better serve our sickest patients. Treatment of malignant gliomas using ganciclovir-hypersensitive, ribonucleotide reductase-deficient herpes simplex viral mutant, Cancer Res. Factor(s) present in herpes simplex virus type 1- infected cells can compensate for the loss of the large subunit of the viral ribonucle- otide reductase: characterization of an ICP6 deletion mutant, Virology, 1988, 166(1), 41–51. Defective herpes simplex virus vectors for the study of promoter and gene function in the CNS, Gene Ther.

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