V. Moff. University of Wisconsin-Madison.
The primary electron beam can be either parallel (57) or slightly convergent (33) buy trimox overnight delivery antibiotic resistance issues, and its precession creates a hollow illumination conec with its vertex on the crystalline sample buy trimox 250mg mastercard antibiotics for dogs after surgery. The precession movement of the primary electron beam around the center of the screen of the transmission electron microscope (Figs buy discount trimox 500 mg online infection xbox 360. The radius of the Laue circle is determined by the precession angle, that is, the half angle of the hollow illumination cone of the precessing primary electron beam. The precession angle can be calibrated on the basis of the radius of the primary electron beam circle in “just-precessed” mode recordings as Figures 3(A) and 3(C). The Ewald sphere will be intersected sequentially at positions that are close to the circumference of the Laue circle [Fig. Note how individual rows of reﬂections are excited sequentially (as much as this is possible with current tech- nology in a transmission electron microscopec) in Figure 4(A) for a precession angle of 2. The short full and dotted arrows represent the double scattering paths that are mainly responsible for the intensity of the kinematically forbidden (002) reﬂection. The hkl arrows points to two reﬂections with indices that are all even but not a modulus of 4, that is, they are kinematically forbidden for this crystal. These reﬂections are also present in the snapshot of (A) where a double-diffraction path that leads to the (222) re¯ ¯ ﬂection over (113) and (111) is marked¯ ¯ ¯ by arrows. Note that the overall intensity distribution in (B) and (C) is far from the “nearly leveled out” intensity distribution that may be caused by strong multiple scattering effects in experimental electron diffraction patterns. In addition, both ﬁgures have essentially the same intensity ordering between the strongest and weakest reﬂections. To appreciate a beneﬁcial side effect of the precessing primary electron beam, note that all electron diffraction patterns arise from the same nanocrystal area in the same crystallographic orientation. Systematic dynamical interactions along such rows are not suppressed by the precession movement of the primary electron beam. More reﬂections allow for least-squares ﬁts to larger sys- tems of inhomogeneous linear equations. This results in more precise determina- tions of projected reciprocal lattice geometries. To appreciate a side effect of the precessing primary beam, note that all of the electron diffraction patterns of this ﬁgure arise from the same nanocrystal area with the same initial beam tilt misalignment with respect to the optical axis of the transmission electron microscope. The reﬂections are kinematically forbidden for silicon, but they are rather strong in all diffraction patterns [Figs. The special term “pertur- bation reﬂections” has been suggested (79) for such reﬂections and their intensity is due to an electron diffraction equivalent of the Renninger (“Umweganregungs”) effect of X-ray diffraction. The subsequent diffraction of the (113) beam on the (111)¯ ¯ ¯ net plane results, for example, in the (222) reﬂection. This can partly be explained by the precession geometry, which tends to excite whole systematic rows at once. As demonstrated in Figures 5 to 7, kinematically forbidden reﬂections, for example, ± and or reﬂections of silicon, are frequently present in electron diffraction patterns as a result of multiple dynamical scattering. The ±(002) reﬂections in the  orientation of silicon arise mainly from the double scattering by the ±(111)¯ ¯ and ±(111)¯ reﬂections. Since these ±(111)¯ ¯ and ±(111)¯ reﬂections possess the largest net plane spacing, the effect of the geometri- cal part of the Lorentz factore on their intensities will be rather signiﬁcant for low Structural Fingerprinting of Nanocrystals in the Transmission Electron Microscope 291 Zero precession 1. All diffraction patterns were recorded close to the amorphized edge region of the sample that borders on the vacuum region within the microscope. The concentric rings in all diffraction patterns arise from the above-mentioned amorphized edge region. The effect of the geometrical part of the Lorentz factore seems to dominate over its structure–thickness- dependent part for this thin crystal and may explain the initial absolute increase of the intensity of the kinematically forbidden ±(002) reﬂections with precession angle. One member of this pair of reﬂections is marked by an arrow in each diffraction pattern. Figure 8 provides a comparison of the effect of the precession angle on the intensity of the ±(002), ±(111), and ±(111) reﬂections for the 6-nm thin silicon nanocrystal of Figure 7 with the corresponding dependency of the thickest silicon nanocrystal of that range, that is, the 56-nm thick silicon nanocrystal of Figure 6. Principally different dependencies of the integrated intensities of kinematically for- bidden and “allowed” reﬂections on the precession angle for both thicknesses are revealed in Figure 8. While there is an exponential decay of the intensities for the ±(002) reﬂections of the thick crystal and an analogous decay with nearly the same slope between 1. These principally different dependencies may allow for a quite unambigu- ous identiﬁcation of some of the kinematically forbidden reﬂections and could be utilized for advanced structural ﬁngerprinting. The normalization was performed by dividing the maximal peak intensity of the reﬂections by the maximal peak intensity of the primary beam. The relative large difference in the intensities of members of the two Friedel pairs in (A) is due to the recording of the diffraction patterns close to the amorphized edge region of the sample, bordering on the vacuum region in the microscope (see caption of Fig. The program “Space Group Determinator” from the Calidris companyf supports such identiﬁ- cations (82). This effect is also demonstrated by the integrated peak intensities of the ±(111) Friedel pair reﬂections in Figure 8(B). Dorset’s correction scheme (37) may, therefore, be developed on the basis of two experimental data sets that differ with respect to their “effec- tive curvature” of the Ewald sphere but are recorded successively from the same crystalline sample area. The extraction of information on the projected reciprocal lattice geometry is very similar for both sources of structural data. One of these parameters 294 Moeck and Rouvimov is the distance of the reﬂection to the reﬂection 000, in other words, the length of the reciprocal lattice vector of this reﬂection. The other parameter is the acute angle this reﬂection makes with another reﬂection. The remaining parameter is the length of the other reciprocal lattice vector that was used in order to deﬁne the (acute) “interfringe angle. Experimen- tal plots of projected reciprocal lattice geometry are thus independent of this orien- tation. Another advantage of this deﬁnition of the position parameters of reﬂections is connected to the ways in which lattice centering and space group symmetry ele- ments with glide component that result in kinematically forbidden reﬂections are dealt with in such plots. For now, it sufﬁces to say that the experimental plots will represent the whole projected reciprocal lattice geometry in a consistent manner. The latter plots can be calculated “on the ﬂy” over the Internet from our mainly inorganic subset (15) of the Crystallography Open Database (16–18) and contain all of the data points for all of the zone axes of a crystalline material up to a predeﬁned resolution in reciprocal space. Identifying a crystal from its projected reciprocal lattice geometry is, thus, frequently equivalent to ﬁnding the 2D data points of the experimental plot within the theoretical lattice-fringe ﬁngerprint plot. Figure 9 shows the theoretical lattice-fringe ﬁngerprint plot for the mineral rutile for a 0. Screw axes and glide planes result in systematic absences of reﬂections in 2D projections of the reciprocal lattice geometry and are revealed in “kinematic lattice-fringe ﬁngerprint plots” by missing rows [compare Figs. The so-called “Gjønnes and Moodie dynamically forbidden reﬂections” (83) are shown in dynamical lattice-fringe ﬁngerprint plots [Fig.
Other adverse reactions Pharmacotherapeutics include: Etoposide is used to treat testicular cancer lymphomas cheap trimox online master card antibiotic resistance yersinia pestis, prostate • nausea and vomiting cancer trimox 250mg generic infection heart rate, and small-cell lung cancer discount trimox 500mg otc bacteria archaea eukarya. Monoclonal antibodies include: • alemtuzumab • gemtuzumab ozogamicin • ibritumomab tiuxetan • rituximab • trastuzumab. Pharmacokinetics Because of their large protein molecule structure, monoclonal an- tibodies aren’t absorbed orally. They may have a limited distribu- tion as well as a long half-life, sometimes measured in weeks. Pharmacodynamics Monoclonal antibodies bind to target receptors or cancer cells and cause tumor death via several mechanisms: They may induce pro- grammed cell death; they may recruit other elements of the im- mune system to attack the cancer cell; or they may deliver a dose of a toxic chemotherapy drug (gemtuzumab) or radiation (ibritu- momab) to the tumor site. Drug interactions Although no interactions have been noted with alemtuzumab, mul- tiple drug interactions are associated with other monoclonal anti- bodies. These agents are derived from tions that have occa- a naturally occurring alkaloid from the Chinese tree Camptotheca sionally been fatal. Currently available topoisomerase I inhibitors in- These include fever, clude: chills, shortness of • irinotecan • topotecan. In addition, the fol- Pharmacokinetics lowing adverse reac- Both irinotecan and topotecan are minimally absorbed and tions can occur: must be given I. Topotecan pression and an in- is metabolized by the liver, although renal excretion is a signifi- creased risk of oppor- cant path for elimination. Topoisomerase I inhibitors act against both solid tumors and hematologic malignancies: • Irinotecan is used to treat colorectal cancer and small-cell lung cancer. Drug interactions Topoisomerase I inhibitors, particularly irinotecan, can interact Adverse with other drugs. Common reactions • Prochlorperazine administered with irinotecan can increase the The more common ad- incidence of extrapyramidal toxicities. Drugs used for this new approach to cancer treat- ment include: and production of saliva • bortezomib • nausea, vomiting, and • gefitinib loss of appetite • imatinib. Pharmacokinetics Additional reactions Bortezomib isn’t absorbed orally and must be given I. It’s exten- Occasionally, these re- sively distributed into body tissues and metabolized by the liver. It’s 95% bound to plasma proteins and is exten- itchy sively metabolized by the liver. Proteolysis by bortezomib results in disruption of the normal homeostatic mech- anisms and leads to cell death. This inhibition blocks signaling pathways for growth, proteins that cause survival, and metastasis of cancer. Pharmacotherapeutics Bortezomib is used to treat multiple myeloma that has relapsed af- ter standard chemotherapy. Gefitinib is used as a single agent for patients with non–small- cell lung cancer that hasn’t responded to two standard chemother- apy regimens. Drug interactions Bortezomib, gefitinib, and imatinib have been associated with some drug interactions. Adverse reactions to targeted therapies Patients should avoid becoming pregnant while taking borte- farction, pulmonary edema, and pericardial effusion (less com- zomib, gefitinib, or imatinib because in animal studies these mon reactions) drugs crossed the placental barrier, causing fetal harm and Gefitinib death. These drugs include: • arsenic trioxide • asparaginases • procarbazine • hydroxyurea • interferon • aldesleukin • altretamine • paclitaxel (taxane) • docetaxel (taxane). Arsenic trioxide is a commercially available treatment for pa- tients with acute promyelocytic leukemia (a rare form of acute myeloid leukemia). The metabolism of arsenic trioxide involves reduc- cause electrocardio- tion via arsenate reductase, with subsequent methylation to inac- gram abnormalities, tive metabolites in urine. Arsenic is distributed in the heart, liver, which could progress to kidney, lung, hair, and nails. It’s also being in- • muscle and bone vestigated for treatment of multiple myeloma. Fever, After administration, asparaginase remains inside the blood ves- headache, abdominal sels, with minimal distribution elsewhere. The metabolism of as- pain, pancreatitis, coag- paraginase is unknown; only trace amounts appear in urine. Pharmacodynamics Rising risk Asparaginase and pegaspargase capitalize on the biochemical dif- Asparaginase and peg- ferences between normal cells and tumor cells. Deprived of their supply of asparagine, the tumor The risk of a reaction ris- cells die. Pharmacotherapeutics Hypersensitivity re- Asparaginase is used primarily in combination with standard actions may also occur. Without If allergic… asparaginase, Pegaspargase is used to treat acute lymphocytic leukemia in pa- I’m finished! Concurrent use of asparaginase with prednisone or vincristine in- creases the risk of toxicity. Adverse reactions to Pharmacokinetics procarbazine After oral administration, procarbazine is well absorbed. Late-onset bone marrow suppression is the most Metabolism and excretion common dose-limiting Procarbazine is metabolized rapidly in the liver and must be acti- toxicity associated with vated metabolically by microsomal enzymes. Respiratory excretion of the drug occurs pneumonitis (lung in- as methane and carbon dioxide gas. Pharmacodynamics An inert drug, procarbazine must be activated metabolically in the A bad start liver before it can produce various cell changes. Pharmacotherapeutics Procarbazine is used in the treatment of Hodgkin’s disease, lym- Gut reactions phoma, and brain cancer. So • Taken with meperidine, it may result in severe hypotension and watch out for death. When your neck is on the line Hydroxyurea is also used for solid tumors and head and neck cancer. Metabolism and excretion About one-half of the dose is metabolized by the liver to carbon dioxide, which is excreted by the lungs, or to urea, which is ex- creted by the kidneys. Adverse Divide and conquer reactions to Hydroxyurea kills cells in the S phase of the cell cycle and holds hydroxyurea other cells in the G1 phase, where they’re most susceptible to irra- diation. Treatment with hydroxy- urea leads to few ad- Pharmacotherapeutics verse reactions. Those that do occur include: Hydroxyurea is used to treat selected myeloproliferative disor- ders. It may produce temporary remissions in some patients with • bone marrow suppres- metastatic malignant melanomas as well. These drugs exhibit anticancer activity as well as activity against condylomata acuminata (soft, wartlike growths on the skin and mucous membrane of the genitalia caused by a virus). The three types of interferons are: alfa interferons derived from leukocytes beta interferons derived from fibroblasts (connective tissue cells) gamma interferons derived from fibroblasts and lympho- cytes. Metabolism and excretion Alfa interferons are filtered by the kidneys, where they’re degrad- ed. Interferons Pharmacodynamics can put a stop to viral Although their exact mechanism of action is unknown, interferons replication.
Warnings/precautions: All warnings provided by the manufac- turer have been set forth as succinctly as possible order 500 mg trimox mastercard bacteria fermentation. Other statements are made to alert the health provider to potential problems with the drug and how to avoid them order 250mg trimox visa infection control today. Advice to patients: This represents our opinions regarding what the treating clinician needs to tell the patient to attempt to avoid or minimize problems with the drug purchase generic trimox online antibiotic resistance deaths. Adverse reactions: These are defined as common (occurring in ≥ 10% of the patients taking the drug in pre- or postmarketing testing) and serious (potentially life threatening or with the risk of causing organ damage). Side effects that are serious as well as common are listed as serious but in boldface type. Clinically important drug interactions: All too frequently, drug compendia list too many such interactions and/or fail to indicate which of these enhance or diminish the actions of a particular drug. Our list of drug interactions includes only those that, by consensus, are clinically relevant and include a statement regarding the actual effect of the interaction. Parameters to monitor: We consider it to be of great importance that the treating clinician follow up on how a drug is acting on the patient by monitoring various vital functions. If these sug- gestions are followed, we believe many serious adverse reactions may be avoided or minimized. Judgment regarding actual monitoring in individual patients must ultimately be made by the treating clinician. Despite our best efforts to provide accurate information and opinions about each drug considered, the authors, members of the Advisory Board, and publisher do not guarantee that all of the material presented is completely accurate. The authors, reviewers, and publishers are not responsible for any errors, either those of omission or commission, that may arise in applying the enclosed information. Furthermore, not all authorities will agree with all our facts and/or evalua- tions. Accordingly, we can consider the material presented only as guidelines for drug administration, not the final word. The clinician or other health care provider must use his or her personal, independent judgment in applying the information in actual practice. In this regard, it is suggested that if the clinician disagrees with something in our drug monograph, he or she should check with the manufacturer’s label for the particular drug before using it. The authors, reviewers, and publisher disclaim any liabil- ity for any claim for losses or alleged losses that may have resulted from the use of the information contained herein whether directly or indirectly applied. The authors, reviewers, and publisher have no connection with any pharmaceutical company or federal agency. This book was commissioned solely by McGraw–Hill Company and the authors have written it without endorse- ment from any pharmaceutical company or federal agency. Any opinions expressed herein are solely those of the authors and members of their Advisory Board. The authors, Advisory Board, and publisher will not be held liable if the material presented is misused or not applied appropriately by the clinician. Inclusion of one or more brand names should not be construed as an endorsement of the product just as its exclusion does not imply that we have rejected the product or consider it inferior to another. The publisher does not endorse or reject any of the products described and has no opinion regarding any of the products. The publisher has not engaged in or provided any kind of financial support for any of the products described herein. Their knowledge and hands-on experience in specialty patient care has added greatly to the depth of information provided by the book. We also acknowledge Catherine Will and Cheryl Serdar for their excellent assistance with manuscript prepara- tion. Special thanks go to Lynn Kaczmarz for administrative assistance with the book and to the editors of McGraw–Hill for their support and encouragement. Seymour Ehrenpreis: My heartfelt thanks to my wife, Bella, for her forbearance throughout the time devoted to the task of writ- ing this book. Eli Ehrenpreis: I would like to dedicate this book to my wife, Ana, for her encouragement and enthusiasm during the writing of the book and to my children, Benjamin, Jamie, and Joseph, for being so understanding and for sacrificing time that could have been spent with their father. Finally, I dedicate this book to my grandfather, the late Joseph Goodman, a man of great wisdom, energy, and humor who inspired me to achieve these qualities in my personal and professional life. Mechanism of action: Competitive blocker of β adrenergic receptors in heart and blood vessels. Adjustment of dosage • Kidney disease: Creatinine clearance 25–50 mL/min: decrease dose by 50%; creatinine clearance <25 mL/min: decrease dose by 75%. If necessary to dis- continue, taper as follows: reduce dose and reassess after 1–2 weeks; if status is unchanged, reduce by another 50% and reassess after 1–2 weeks. Advice to patient • Avoid driving and other activities requiring mental alertness or that are potentially dangerous until response to drug is known. Clinically important drug interactions • Drugs that increase effects/toxicity of beta blockers: reserpine, bretylium, calcium channel blockers. Stop therapy and administer large doses of β-adrenergic bronchodilator, eg, albuterol, terbutaline, or aminophylline. Some advocate discontinuing the drug 48 hours before surgery; others recommend withdrawal for a considerably longer time. These are drugs of first choice for chronic stable angina, used in conjunction with nitroglycerin. Mechanism of action: Stimulates release of insulin from pancre- atic beta cells; decreases glucose production in liver; increases sensitivity of receptors for insulin, thereby promoting effective- ness of insulin. Dose is best administered before breakfast or, if taken twice a day, before the evening meal. Contraindications: Hypersensitivity to the drug; diabetes com- plicated by ketoacidosis. Editorial comments • This drug is not listed in Physician’s Desk Reference, 54th edi- tion, 2000. Mechanism of action: As mucolytic agent: disrupts disulfide bonds in mucoproteins thereby lowering viscosity of mucus. As antidote for acetaminophen poisoning: complexes with hepato- toxic free radial metabolite of acetaminophen and inactivates it. Onset of Action Duration 5–10 min >1 h Food: Given before meals and just before bedtime for asthma. Warnings/precautions • As antidote for acetaminophen poisoning: Administer as quickly as possible. If this occurs, administer bronchodilator; suction bronchial secretions if they develop after inhalation. Advice to patient: Rinse mouth out and wash face after treatment to remove adhering drug.