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By X. Irhabar. Indiana University - Purdue University, Indianapolis.

Since for 511 keV photons the stopping power of sodium iodide is relatively poor order depakote 250 mg otc medications osteoporosis, manufacturers offer thicker crystals than normal (up to 25 mm thick) order depakote 500mg visa medicine pacifier, with only slightly poorer resolution discount 500mg depakote free shipping symptoms viral meningitis, due to uncertainty in the location of detected events. The ability to maintain performance is largely attributable to the improved design of recent gamma cameras. It should be recalled that the absence of a collimator means that the resolution is essentially defined by the intrinsic resolution of the gamma camera at 511 keV (typically 4. Dual head systems rotate to different angles around the patient, recording coincidences at each angle. Although the earlier systems did not include attenuation correction, recent systems now have this as an option. Nevertheless, their introduction has resulted in the widespread use of positron emitting tracers in clinical practice. Use of ultrahigh energy collimators A very simple approach to imaging 511 keV photons is to use an ultrahigh energy collimator. Although coincidence imaging was used initially in oncology studies, it has since become evident that only fairly large tumours can be detected. Purchase of dual photon imaging systems All nuclear medicine physicians, assisted by a nuclear medicine physicist, acquire some experience during their careers in purchasing gamma cameras and other accessories for a nuclear medicine service. The decision making process, leading to the purchase of a system performing dual photon imaging, calls for knowledge of the basic physics of coincidence detection and of the differences between 2-D and 3-D acquisition in terms of sensitivity, the ratios between the true and the random events, and scatter fraction, as well as the different methods to overcome these problems. There are a number of different ways to increase the sensitivity of the system and physicians should work closely with a physicist who has extensive knowledge of these areas. It is recommended that they should visit or contact a site that is already functioning. They should also have an opportunity to observe on the workstation the studies performed. The nuclear medicine physicist should be able to review the results of the various quality control tests performed. There are many aspects of purchasing dual photon imaging systems that are common to the purchasing of single photon imaging systems; these have been covered in an earlier section of this chapter. In addition to specific advice on contractual arrangements, warranty and service, the reader should bear the following points in mind when purchasing dual photon imaging equipment. In most cases the primary purpose of purchasing the equipment is to perform oncology studies, although specific centres may have research require- ments in other areas. The main considerations in choosing between the systems can be summarized as follows. The effect of increasing crystal thickness on routine single photon nuclear medicine studies should be considered. Although a slight decrease in resolution is demonstrated in bar phantom studies, it has little effect on routine clinical studies. An advantage is the additional increase in the sensitivity for such radionuclides as 67 111 131 Ga, In and I. Sensitivity is improved by using 3-D rather than 2-D acquisition as outlined in the sections earlier in this chapter. The exact trade-off in useful counts (with scatter correction) for whole body applications continues to be evaluated. There are several approaches to improve count rate capability with specific circuitry designed to enhance the performance of gamma camera based systems. A further constraint is the period required to measure attenuation in these studies. This makes the total time required for whole body acquisition a critical factor in determining the utility of a system. In addition, since iterative reconstruction is commonly used instead of filtered back-projection, processing can be relatively slow. The total time of examination including processing should be taken into consideration. This can be a major consideration in situations where patient numbers or radionuclide supply may be limited. New develop- ments in detector technology are likely to result in a wider range of hybrid systems. It should be noted that the technology used in dual photon imaging is changing rapidly. The emphasis of this document is on instruments designed for whole body applications, although additional tests are included that provide comparative information related to other types of application. The major advance in this document is that no distinction is made between conventional and gamma camera based systems.

For measurement of kidney function order 250mg depakote with amex medicine 906, the ideal counting system has three probes: one for each kidney plus one to measure the blood and tissue background buy 500 mg depakote overnight delivery medications heart failure. When purchasing a probe system cheap 500 mg depakote overnight delivery medications 142, one must ensure that a set of low activity spectrum calibration sources is provided. These are crucial, as they are used to set the single channel spectrum analyser to the required counting energy. The sources should have a relatively long half-life, a distinct photon energy (or energies), and cover the required energy range, usually 60–511 keV. Surgical gamma probes The use of surgical probes for localization of activity which can be traced and surgically excised has been of interest since 1949. In this section emphasis is placed on the use of probes employed for detection of 99mTc radiopharmaceuticals. The technique of sentinel node localization needs multidisciplinary co- operation between nuclear medicine physicians, surgeons and pathologists. Success in detecting the sentinel node depends on many factors related to the sensitivity of the detector, the spatial and energy resolution and geometric efficiency of the detector, the radiopharmaceutical injected, the rate of clearance from the site of injection and the uptake in the sentinel node. Detectors are made by various manufacturers, and the preference between different types requires knowledge of the basic physics principles, which are summarized below. Is it for the purpose of sentinel node localization only for early breast cancers and malignant melanomas or for the intraoperative detection of residual or recurrent tumours such as colorectal cancer, thyroid cancer or parathyroid adenoma? The user must familiarize him/herself with different probes and have experience in operating them. A surgical gamma probe is based on either a scintillation detector or a semiconductor detector. Scintillation detectors consist of either NaI or CsI, either 14 or 19 mm in diameter, with a photomultiplier tube and amplifier. The signal intensity of scintillation detectors is higher than that of semiconductor detectors, but their energy discrimination is inferior. Semiconductor detectors consist of either cadmium telluride or, more recently, cadmium zinc telluride. They are significantly more compact than scintillation detectors and therefore more suitable for intraoperative use. When purchasing a probe system for use in surgery, the following factors should be taken into consideration: (a) Shielding (collimation) from scattering is important for improved local- ization and improved spatial resolution. Shielding may be either integral in the design of the probe or in the form of removable collars of a heavy attenuating material. It is advisable to use collimators when there is adjacent activity next to the sentinel node. Well counters Well counters are used for low activity, high efficiency counting of in vitro samples, and are available either as manually operated single sample (or limited number of samples) devices or as fully automatic, multiple sample counters. All well counters use large volume NaI detectors in the form of a well, where the sample is virtually surrounded by the detector. Ideally, they should have the following capabilities: —Automatic photon spectrum calibration, with continuous correction for drift; —Ability to select and count multiple radionuclides; —Automatic radioactive decay correction for the selected radionuclide(s); —Variable counting time; —Sample identification; —A printed report for each sample including sample identification, counting time, energy selected and counts; —An indication of errors in the electronics or mechanical sample changer. Purchasing a nuclear medicine computer Computers have been central to the practice of nuclear medicine for many years, particularly as the extraction of functional information commonly necessitates image analysis. Computers form an integral part of imaging equipment, providing on-line acquisition and data correction to improve instrument performance, essential functions such as tomographic recon- struction and flexible display of images. As computer speed increases exponen- tially, and with memory and disk capacity showing similar growth, the capacity of the computer to tackle more complex and challenging tasks in a clinically acceptable time increases. Patient throughput and efficiency of operation are greatly aided by the computer tools available. By adopting these relatively highly developed and widely used computer systems, for which numerous hardware and software options are available, the vendors are now able to offer support for industry standards in several important areas, including networking. When purchasing nuclear medicine equipment it is usual to include a computer supplied from the same manufacturer, although there are instances where computers may be purchased separately. Choice of equipment should be based on the criteria outlined in earlier sections, with choice of computer being secondary to general considerations such as the amount of support available. Since computers are increasing in performance so rapidly, the main problem with them is that they have a much shorter life than that of the associated imaging equipment. The limitation therefore is in the ability to upgrade systems so that software and new features are available. Continuation of a software support contract is advisable as this will normally include any improvements, fixes of any bugs and new releases for a reasonable time. However, at some stage, hardware will also need to be upgraded at the customer’s cost to permit operation of the current software.

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The evidence of male-mediated developmental toxicology Male reproductive exposures are now strongly suspected of causing not only infertility but also miscarriage depakote 500mg on line medications knee, low birth weight buy 250 mg depakote visa medicine 20, congenital abnormalities discount depakote 250mg overnight delivery treatment episode data set, cancer, neurological illness and other childhood health problems (Davis et al. Studies of male reproductive health and toxicity have Between fathers and fetuses 121 concentrated primarily on the eVects of occupational and environmental exposures of men and less on the eVects of what scientists refer to as men’s ‘lifestyle factors’, such as drinking, smoking, or drug use (Davis et al. Because adult males continuously produce sperm throughout their lives, the germ cells from which sperm originate are continuously dividing and developing. Sperm take approximately 72 days to develop to maturity, and then move for another 12 days through the duct called the epididymis, where they acquire the ability to fertilize an egg. During this developmental process, sperm may be particularly susceptible to damage from toxins because cells that are dividing are more vulnerable to toxicity than cells that are fully developed and at rest, as are eggs in the female reproductive system. Abnor- mal sperm may still be capable of fertilizing an egg because speed may be more important than size or shape, as was suggested in the earliest article on this subject (Moore, 1989). Some of the earliest epidemiological research studied the eVects of radi- ation exposures on the children born to men who survived the atomic bombs at Nagasaki and Hiroshima. However, few associations were found between paternal exposures and childhood health problems, possibly due to the fact that so few men conceived children in the six months after the bombing, when the exposure eVects of radiation were at their strongest (Yoshimoto, 1990; Olshan and Faustman, 1993). Vietnam veterans concerned about the eVects of the herbicide Agent Orange called for studies on links between male exposures during the war and childhood diseases of their oVspring. Other studies also showed increased rates of spinal malformation, spina biWda, congenital heart defects and facial clefting in the children of Vietnam veterans. Seventeen studies have now evaluated the impact of pesticides and herbicides on male reproduction and paternal–fetal health (Olshan and Faustman, 1993: p. Other studies have analysed the eVects of occupational exposures on paternal–fetal health, with many Wnding signiWcant associations between paternal exposures and fetal health problems. Paints, solvents, metals, dyes and hydrocarbons have been asso- ciated with childhood leukaemia and childhood brain tumours (summarized in Olshan and Faustman, 1993: p. In analyses by occupation, janitors, mechanics, farm workers and metal workers have been reported to have an excess number of children with Down’s syndrome (Olshan and Faustman, 1993: p. Painters and workers exposed to hydrocarbons have also been shown to have higher rates of children with childhood leukaemia and brain tumours (Savitz and Chen, 1990). And, as in all epidemiological studies, it is diYcult to control for confounding factors, such as the eVects of multiple chemical exposures and alcohol or drug use. However, whilst the problem of confounding variables is common to all epidemiological studies of reproduc- tive toxicity, for cultural reasons scientists are more acutely aware of method- ological caveats when studying men. For instance, studies of paternal eVects are routinely criticized for not controlling for maternal exposures, while studies on women virtually never control for the exposures of fathers. Studies that do focus on the eVects of lifestyle factors on men’s reproduction are criticized for not controlling for men’s workplace exposures, while studies of women and drug use do not control for women’s occupational exposures. The biological processes of male-mediated teratogenicity have also been examined through clinical studies on animals and studies of the eVect of toxic exposures directly on sperm. In a study of more than 14 000 birth records in San Francisco, researchers found associations between paternal smoking and various birth defects, including cleft lip, cleft palate and hydrocephalus (Savitz, Schwingle and Keels, 1991). SigniWcant associations have also been found between paternal smoking and brain cancer in children, and between paternal smoking and low birth weight – a diVerence of up to 238 grams (c. In addition, cotinine, a meta- bolite of nicotine, has been found in seminal Xuid, although researchers are unsure what eVect this might have on fetal health (Davis et al. Bruce Ames of the University of California, Berkeley, has suggested that the link between smoking and birth defects could be due to smokers’ low levels of vitamin C. Case reports suggest an association between paternal drinking and ‘malformations and cognitive deWciencies’ in the children of alcoholic men (Little and Sing, 1987; Colie, 1993: p. Ricardo Yazigi, Randall Odem and Kenneth Polakoski discovered that cocaine could bind to sperm and thereby be transmitted to the egg during fertilization. Reports of cocaine ‘piggybacking’ on sperm have led to controversy in the scientiWc community over whether this phenomenon could contribute to birth defects (Brachen et al. In animal studies, opiates (such as morphine and methadone) administered to fathers, but not to mothers, have produced birth defects and behavioural abnormalities in the Wrst and second generations of the father’s oVspring (Friedler and Wheeling 1979; Friedler, 1985). Press coverage of male-mediated harm The scientiWc evidence on male-mediated risks has generated quite diVerent stories in popular magazines and newspapers than it has for women. Whilst images of crack babies and irresponsible mothers prevail in stories about maternal exposures to drugs, visual images in popular science magazines and news stories about male reproduction place sperm in the centre of focus as the tiniest victims of toxicity. Even in newspaper stories that address the connection between paternal exposures and fetal health, certain patterns of reporting emerge that function to reduce male culpability for fetal harm. In all of the stories that draw connections between paternal exposures and fetal harm, maternal exposure was also mentioned as a possible source of harm. Evidence of male-mediated risks are often prefaced with statements such as, ‘While doctors are well aware of the eVects that maternal smoking, drinking and exposure to certain drugs can have on the fetus, far less is known about the father’s role in producing healthy oVspring’ (Merewood, 1992: p. News and World Report began an article on paternal–fetal harm in these terms, ‘It is common wisdom that mothers-to-be should steer clear of toxic chemicals that could cause birth defects. Between fathers and fetuses 125 Fourth, paternal exposures to illegal drugs are always contextualized by reference to ‘involuntary’ environmental and workplace exposures, thereby reducing men’s culpability for harm. After reporting that children of fathers who smoke have been found to be at increased risk for leukaemia and lymphoma, the article ends with the recom- mendation of a physician that men who smoke ‘either modify their diets to include fruits and vegetables or take a vitamin C supplement each day’. While sperm ‘delivers’, ‘transports’ or ‘carries’ the drug to the egg in such stories, it never ‘assaults’ the fetus, as stories on drug use and women imply.

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In asymptomatic persons depakote 500mg visa medicine 0025-7974, bin lead to reduced tissue oxygenation and the levels up to 20% may require no treatment depakote 250mg on line chapter 9 medications that affect coagulation, but symptoms associated with methemoglobinemia cheap 500mg depakote treatment 5ths disease. High tion of acute symptoms, and there are some studies levels of methemoglobin turn blood brown, and that support the notion that it protects the patient the blood does not turn red when exposed to air. Dysregulated argi- Pulse oximeters may read falsely high oxyhemo- nine metabolism, hemolysis-associated pulmonary globin levels, and when methemoglobin levels of hypertension and mortality in sickle cell disease. Sickle is established using cooximetry, which measures cell chronic lung disease: prior morbidity and the oxyhemoglobin, deoxyhemoglobin, carboxyhemo- risk of pulmonary failure. J Clin Gastro- This “state of the art” article develops the hypothesis that enterol 2004; 38:52−58 oxidant-antioxidant disturbances are pivotal to the develop- Useful review of current concepts. Patients had histology Engl J Med 2008; 358:2378−2387 of bronchiolitis obliterans organizing pneumonia, suggest- Thorough review of the mechanisms, clinical features, diag- ing an immunologic mechanism. Radiographics 2004; 24:861−880 24: 985−997 Reviews hepatopulmonary syndrome and portopulmonary Review of radiation techniques and types of radiation- hypertension, with recommendations for diagnosis and induced injury, with excellent images. The daily fraction size, number of daily frac- Review of the histopathology associated with oxygen pulmo- tions, and total dose were associated with the risk of radia- nary injury. Chest Med 2002; 347:1057−1067 1997; 111:671−675 Three hyperbaric oxygen treatments reduced the incidence Emphasizes the value of laryngoscopy in patients with smoke of the delayed emergence of cognitive dysfunction by almost inhalation. Methemoglobin- of inhalational airway disorders than clinical, laboratory, emia complicating topical lidocaine used during endo- and radiographic findings. Benzo- In a retrospective review of 1,665 patients with acute burn caine-induced methemoglobinemia: experience from a injuries, three risk factors for death were identified: age 60 high-volume transesophageal echocardiography labo- years, 40% of body surface area burned, and inhalation ratory. Although some sta- Key words: medical statistics; probability; receiver operator curves tistical tests are fairly rigorous (ie, insensitive to the violation of assumptions), the results will be ques- tionable if an incorrect statistical test is used. Minor study flaws (eg, randomization, Introduction use of appropriate controls, and double blinding) will limit confidence in the results that have been A firm understanding of medical statistics is analyzed, even those that use the proper statistical vitally important for interpreting the medical lit- tests. This was nicely captured in Mark Twain’s als found that studies with inadequate conceal- infamous remark regarding statistics: “There are ment had a 41% greater treatment effect compared lies; damn lies and statistics. Thus, statistics test to medical students, residents, pri- studies with the most appropriate methodologic vate attending physicians, and academic attending design demonstrate the least benefit of selective physicians and found that the percentages of cor- decontamination of the gut on the incidence of rect answers were 73%, 70%, 55%, and 74%, respec- ventilator-associated pneumonia and, as such, tively. Thus, physicians ing that there is a pathologic supply dependence require a better understanding of the fundamen- of oxygen utilization in which, unlike the normal. Any measured parameter has some distribu- In experimental research, some variables are tion within a study population (eg, Gaussian, uni- manipulated, and then the effects of this manip- form, skewed right, skewed left, bimodal, u-shaped, ulation on other variables are assessed (eg, exponential, and others). Experimental data distribution with a size and shape in patients with are the only conclusive way to demonstrate and without disease that may be completely dis- causal relations between variables. There ple, we can infer that “A influences B” if altera- are statistical tests for assessing whether a sampled tions in variable A result in predictable changes variable has been drawn from a population with in variable B. Occasionally, items that are manipulated in the experimen- a non-Gaussian distribution can be transformed to tal research, whereas dependent variables are be Gaussian (ie, a logarithmic transformation of those items that are only measured and are data skewed to the right, such as length of stay in never manipulated experimentally. The assumption that data have a X1 is a symbol referring to the N individual val- particular distribution is important and prone to ues of your distribution. For example, if 25 of few patients with a very long length of stay will 100 patients without asthma have a positive substantially move the mean upward but will methacholine challenge result, then the speci- have very little if any impact on the median, ficity of the methacholine challenge is 75% which gives us a more accurate indication of (75/[75 25]). In contrast, an extramural grant score ing that there is “no statistically significant of 150 that is in the 5th percentile indicates difference” between the two groups. The null that only 5% of grants have lower scores that hypothesis rejected is the same as saying that is are better (similar to golf, in which low scores highly likely that there is a “statistically signifi- are better in grading grants). In summary, when interpreting data sets, it is • Variance: defined as a measure of the “spread” of important to identify the central tendency as well the data distribution. For when a data set has a Gaussian distribution very small samples, the minimum and maximum is it true that 95% of values in the sample fall values (range) should be listed. Statistics often are performed to assess samples or a set of samples that are taken from the study Student t Test for Comparing Means population to make assumptions about the entire population. An unpaired t test should be used if there are Gaussian regardless of the distribution in the different persons in the two groups (eg, separate underlying population (ie, the central limit theo- groups of normal patients and asthma patients) to rem). Therefore, we use the sampling distribution not a true difference between two sample groups to tell us how unlikely it is that two samples that requires an adequately sized N value to ensure that are drawn from the same populations will have a the two group means are far enough apart to difference in the size observed. Sample size 298 Medical Statistics/Test-Taking Strategies (Kamp) is calculated by choosing a numerical value for Bonferroni correction, which is a very rigorous way and and by using some reasonable estimates to maintain protection against type I errors and is from the available literature about the estimated calculated by dividing the chosen p value (0. Sample size determination should always hypotheses (ie, if we do 10 pairwise comparisons, be performed before the study and not after the the adjusted p value would be calculated as study to validate the results. Although many studies identify a pri- Nonparametric statistical testing uses ranks rather mary outcome, secondary outcomes with an unad- than the actual numerical values so that the aver- justed p 0. The best index trary cut point between normal and abnormal to use in describing the data depends on that which based on studies in patients with and without the you are examining. Calculating measures of discrimination of a new serum test (T) to detect mesothelioma (D) in a group of asbestos workers with a mesothelioma prevalence of 20%. In this instance, the best cut point for a test Sensitivity and specificity alone are inadequate result is one that is located in the upper-most left- to meaningfully understand the implications of a hand corner of the graph.