By I. Bozep. East Carolina University.
However discount antabuse 250mg with mastercard medicine engineering, this early assumption has been questioned with reports of intraparenchymal hemorrhage detected by MRI within 6 hours cheap 500 mg antabuse fast delivery symptoms women heart attack, and as early as 23 minutes from symptom onset (24–26). One of the studies prospectively demonstrated that MRI detected all nine patients with CT-conﬁrmed intracerebral hemorrhage (ICH), suggesting the potential of MRI for the hyperacute evaluation of stroke (limited evidence) (24–26). More recently, a blinded study comparing MRI (diffusion-, T2-, and T2*- weighted images) to CT for the evaluation of ICH within 6 hours of onset demonstrated that ICH was diagnosed with 100% sensitivity and 100% accuracy by expert readers using MRI; CT-detected ICH was used as the gold standard (strong evidence) (9). Data regarding the detection of acute subarachnoid and intraventricular hemorrhage using MRI is limited. While it is possible that the conversion of blood to deoxyhemoglobin occurs much earlier than expected in hypoxic tissue, this transition may not occur until much later in the oxygen-rich environment of the CSF (20,27). Thus the susceptibility-weighted sequence may not be sensitive enough to detect subarachnoid blood in the hyper- acute stage. This problem is further compounded by severe susceptibility artifacts at the skull base, limiting detection in this area. The use of the ﬂuid-attenuated inversion recovery (FLAIR) sequence has been advocated to overcome this problem. Increased protein content in bloody CSF appears hyperintense on FLAIR and can be readily detected. Three case-control series using FLAIR in patients with CT-documented subarachnoid or intra- ventricular hemorrhage demonstrated a sensitivity of 92% to 100% and speciﬁcity of 100% compared to CT and was superior to CT during the sub- acute to chronic stages (limited evidence) (28–30). Hyperintense signal in the CSF on FLAIR can be seen in areas associated with prominent CSF pul- sation artifacts (i. At later time points in hematoma evolution (subacute to chronic phase) when the clot demonstrates nonspeciﬁc isodense to hypodense appearance on CT, MRI has been shown to have a higher sensitivity and speciﬁcity than CT (limited evidence) (28,34,35). The heightened sensitivity of MRI susceptibility-weighted sequences to microbleeds that are not otherwise detected on CT makes interpretation of hyperacute scans difﬁcult, espe- cially when faced with decisions regarding thrombolysis (Fig. Patient outcome regarding the use of thrombolytic treatment in this subgroup of patients with microbleeds is not known; however, in one series of 41 patients who had MRI prior to intraarterial tPA, one of ﬁve patients with microbleeds on MRI developed major symptomatic hemorrhage compared to three of 36 without (36), raising the possibility that the presence of microbleeds may predict the subsequent development of symptomatic hemorrhage following tPA treatment. As this ﬁnding was not statistically signiﬁcant, a larger study is required for conﬁrmation. Top row: Two sequential magnetic resonance (MR) images of T2* sequence show innumerable small low signal lesions scattered throughout both cerebral hemispheres compatible with microhemorrhages. Bottom row: Noncontrast axial computed tomography (CT) at the same anatomic levels does not show the microhemorrhages. What Are the Imaging Modalities of Choice for the Identiﬁcation of Brain Ischemia and the Exclusion of Stroke Mimics? Summary of Evidence: Based on moderate evidence (level II), MRI (diffusion-weighted imaging) is superior to CT for positive identiﬁcation of ischemic stroke within the ﬁrst 24 hours of symptom onset, allowing exclusion of stroke mimics. However, some argue that despite its superi- ority, positive identiﬁcation merely conﬁrms a clinical diagnosis and does not necessarily inﬂuence acute clinical decision making or outcome. Computed Tomography Computed tomography images are frequently normal during the acute phase of ischemia and therefore the diagnosis of ischemic stroke is con- 166 K. Based purely on history and physical examination alone without conﬁrmation by CT, stroke mimics can account for 13% to 19% of cases initially diagnosed with stroke (37,38). Sensitivity of diagno- sis improves when noncontrast CT is used but still 5% of cases are misdi- agnosed as stroke, with ultimate diagnoses including paresthesias or numbness of unknown cause, seizure, complicated migraine, peripheral neuropathy, cranial neuropathy, psychogenic paralysis, and others (39). An alternative approach to excluding stroke mimics, which may account for the presenting neurologic deﬁcit, is to directly visualize ischemic changes in the hyperacute scan. Increased scrutiny of hyperacute CT scans, especially following the early thrombolytic trials, suggests that some patients with large areas of ischemia may demonstrate subtle early signs of infarction, even if imaged within 3 hours after symptom onset. These early CT signs include parenchymal hypodensity, loss of the insular ribbon (40), obscuration of the lentiform nucleus (41), loss of gray–white matter differentiation, blurring of the margins of the basal ganglia, subtle efface- ment of the cortical sulci, and local mass effect (Fig. It was previously believed that these signs of infarction were not present on CT until 24 hours after stroke onset; however, early changes were found in 31% of CTs per- formed within 3 hours of ischemic stroke (moderate evidence) (42). A: Noncontrast axial CT performed at 2 hours after stroke onset shows a large low-attenuated area involving the entire right middle cerebral artery distribution (bounded by arrows) with associated effacement of the sulci and sylvian ﬁssure. There is obscuration the right lentiform nucleus (*) and loss of the insular ribbon (arrowhead). B: Follow-up noncontrast axial image 4 days later conﬁrms the infarction in the same vascular distribution. There is hemorrhagic conversion (*) in the basal ganglia with mass effect and subfalcine herniation. Chapter 9 Neuroimaging in Acute Ischemic Stroke 167 tion, early CT signs were found in 81% of patients with CTs performed within 5 hours of middle cerebral artery (MCA) stroke onset (demonstrated angiographically) (moderate evidence) (43).
At this configuration buy 250mg antabuse free shipping medications for ocd, the tube is stressed; the outer layer is under tension and the inner layer is under compression order antabuse 250 mg with visa ad medicine. Similar to the in- verted cylindrical tube, ringlike specimens of animal aortas spring open after being cut in the radial direction, indicating that natural configura- tion of some biological tissues is not stress free. Regardless of the state of motion, external forces acting on a body will cause internal stresses within the body. It is impossible to directly deter- mine the system of forces carried by the muscles, the ligaments, and the joint articular surfaces in the human and animals. The number of load-transmitting elements at a joint almost always exceeds the number of equations gov- erning the motion of that joint. This joint has a multitude of ligaments that hold it to- gether and a large number of muscles acting on it. Even in the simplest weight-lifting exercises, multiple muscles will contribute to the lifting of the weight. How do we estimate the forces carried by various ligaments, muscles, and bones, given the external forces acting on the body? The first step is to draw a free-body diagram of a body part in which all forces acting on it are clearly laid out. Then, one considers the equa- tions of motion (or static equilibrium) to compute the unknown forces shown in the diagram. Typically, the unknown forces carried by a pas- sive structures (capsules, ligaments, and the bones) intersecting at a joint 150 6. The lateral view of the knee joint (a, posterior; b, sagittal) and some of the ligaments associated with it. In the presence of large muscle moments acting on a joint, the moment created by pas- sive structures on the rotational center of the joint may be negligible. This is however not true during impact loading where ligaments are maxi- mally stressed to keep the joint intact. In allocating forces to various muscle groups involved in posture, movement, and motion, two general approaches have been used—the reduction method and the optimization method. In the optimization technique, one assumes that muscles exert forces on bones near joints according to the minimization of some performance criterion. A large number of optimization criteria, including ad hoc principles of minimal muscle force, minimal muscle stress, and minimal energy expenditure or consumption, have been utilized. The method is attractive because sequences of movement in locomotion appear to suggest an intrinsic op- timization process achieved through learning. This point can be illus- trated with the consideration of vertical jumping where the position of the upper body is determined by the angles at the hip, knees, ankles, and metatarsal heads. The system has four degrees of freedom and thus our body allows the jumping task to be executed in a variety of ways. Yet, after practice, most movement tasks that lead to jumping seem to be performed in stereotyped manners. The sequence of muscular acti- vation appears to be always in the order of upper body, upper legs, lower legs, feet, suggesting an optimization process. The biomechanics literature contains many examples of the application of optimization techniques in the study of the shoulder, hip, and knee. Internal Forces and the Human Body cles on the subject for further exploration of the merits and weaknesses of this approach. The method of reduction is much simpler mathematically than the method of optimization. It is essentially the reduction of the number of unknown forces acting at a joint to a number of available equations of mechanics. Electromyographic (EMG) signals are often used as guides to choose muscles that actuate a certain movement. A common assumption in calculating the force produced by the agonist is to set the force pro- duced by antagonistic muscles equal to zero.
The inclusion in system atic reviews of irrelevant studies is guaranteed to lead to absurdities and reduce the credibility of secondary research discount antabuse 500 mg amex medications similar to gabapentin, as Professor Sir John G rim ley Evans argued (see section 9 buy discount antabuse 250 mg line treatment whiplash. The 128 PAPERS TH AT SU M M ARISE OTH ER PAPERS m etaanalysis, defined as a statistical synthesis of the numerical results of several trials which all addressed the same question, is the statisticians’ chance to pull a double wham m y on you. First, they phase you with all the statistical tests in the individual papers and then they use a whole new battery of tests to produce a new set of odds ratios, confidence intervals, and values for significance. As I confessed in Chapter 5, I too tend to go into panic m ode at the sight of ratios, square root signs, and half-forgotten G reek letters. But before you consign m etaanalysis to the set of newfangled techniques which you will never understand, rem em ber two things. A good m etaanalysis is often easier for the non-statistician to understand than the stack of prim ary research papers from which it was derived, for reasons which I am about to explain. Second, the underlying statistical techniques used for m etaanalysis are exactly the sam e as the ones for any other data analysis – it’s just that som e of the num bers are bigger. H elpfully, an international advisory group have com e up with a standard form at for m eta-analyses (the QU OROM statem ent,20 analogous to the CON SORT form at for random ised controlled trials I m entioned in Chapter 4). The first task of the m etaanalyst, after following the prelim inary steps for system atic review in Figure 8. In trials of a particular chem otherapy regim en for breast cancer, for exam ple, som e authors will have published cum ulative m ortality figures (i. The m etaanalyst m ight decide to concentrate on 12 m onth m ortality because this result can be easily extracted from all the papers. H e or she m ay, however, decide that three m onth m ortality is a clinically im portant endpoint and would need to write to the authors of the rem aining trials asking for the raw data from which to calculate these figures. In addition to crunching the num bers, part of the m etaanalyst’s job description is to tabulate relevant inform ation on the inclusion criteria, sam ple size, baseline patient characteristics, withdrawal ("dropout") rate, and results of prim ary and secondary endpoints of all the studies included. If this task has been done properly, you 129 H OW TO READ A PAPER will be able to com pare both the m ethods and the results of two trials whose authors wrote up their research in different ways. Although such tables are often visually daunting, they save you having to plough through the m ethods sections of each paper and com pare one author’s tabulated results with another author’s pie chart or histogram. These days, the results of m eta-analyses tend to be presented in a fairly standard form. This is partly because m etaanalysts often use com puter software to do the calculations for them ,21 and this software includes a standard graphics package which presents results as illustrated in Figure 8. I have reproduced in the form at of one com m only used software package (with the authors’ perm ission) this pictorial representation (colloquially known as a "forest plot" or "blobbogram ") of the pooled odds ratios of eight RCTs which each com pared coronary artery bypass graft (CABG ) with percutaneous coronary angioplasty (PTCA) in the treatm ent of severe angina. The horizontal line corresponding to each trial shows the relative risk of death or heart attack at one year in patients random ised to PTCA com pared to patients random ised to CABG. The "blob" in the m iddle of each line is the point estim ate of the difference between the groups (the best single estim ate of the benefit in lives saved by offering CABG rather than PTCA) and the width of the line represents the 95% confidence interval of this estim ate (see section 5. The black line down the m iddle of the picture is known as the "line of no effect" and in this case is associated with a relative risk (RR) of 1. In other words, if the horizontal line for any trial does not cross the line of no effect, there is a 95% chance that there is a "real" difference between the groups. The various individual studies give point estim ates of the relative risk of PTCA com pared to CABG of between about 0. This represents the pooled data from all eight trials (overall relative risk PTCA:CABG = 1. Since the diam ond firm ly overlaps the line of no effect, we can say that there is probably little to choose between the two treatm ents in term s of the prim ary endpoint (death or heart attack in the first year). N ow, in this exam ple, every single one of the eight trials also suggested a non-significant effect, but in none of them was the sam ple size large enough for us to be confident in that negative result. N ote, however, that this neat little diam ond does not m ean that you m ight as well offer a PTCA rather than a CABG to every patient with angina. It has a m uch m ore lim ited m eaning – that the average patient in the trials presented in this m etaanalysis is equally likely to have m et the prim ary outcom e (death or heart attack 131 H OW TO READ A PAPER Figure 8.
A novel use of an MR contrast agent was reported for investigating nodes (30); administration of nanoparticles permitted identi- ﬁcation of nonenlarged nodes (118) with focal regions of tumor and per- mitted 100% sensitivity in identifying patients with nodal metastases order antabuse 500 mg on-line symptoms 6 days before period. Investigators have also presented data regarding the ability of MRI ﬁnd- ings to predict posttherapy PSA failures (106 500mg antabuse otc section 8 medications,109,111,119,120) and positive margins in surgical specimens (121). MRI in combination with other data permitted improvements of these prediction rates, but, as in evaluations of its ability to predict exact stage, did not achieve accuracies of 100%. Given the inability of MRI to achieve very high degrees of accuracy among all patients undergoing initial evaluation for prostate cancer, attempts have been made to ﬁnd some groups in which MRI might be particularly useful. One of these investigations found that if MRI were limited to a subgroup of those with a Gleason score of 5 to 7 and a PSA higher than 10 to 20ng/mL, increased accuracy for both extracapsular extension and seminal vesicle invasion could be achieved (107). Another study investi- gated only the ability of MRI to detect enlarged nodes, and suggested that the examination could be withheld from patients with a serum PSA of less than 20ng/mL (122). In summary, MRI probably permits better local staging than older tech- niques in certain subgroups of patients but with considerably less than 100% accuracy; the inability to detect microscopic invasion remains an important limitation, as does the inability to detect disease in nonenlarged lymph nodes with standard techniques. These facts have led to only cau- Chapter 7 Imaging in the Evaluation of Patients with Prostate Cancer 129 tious and scattered acceptance of the technique. Currently, it is probably wise to restrict its use to a subgroup of patients—those whose physical examination, PSA, Gleason score, results of standard workup for metasta- tic disease, and personal preferences leave them on the cusp of choosing surgery or local radiotherapy. When interpreting examinations in these patients, it should be remembered that diagnosis or exclusion of micro- scopic invasion cannot be performed with accuracy, but that visualization of gross tumor extension beyond the capsule or into the seminal vesicle is a relatively speciﬁc sign of invasive disease. Magnetic Resonance Spectroscopic Imaging In addition to high spatial resolution imaging by proton MRI, technology for spatially resolved spectroscopy of the prostate has been under devel- opment for some years. Proton spectroscopic data can be acquired from a three-dimensional array of voxels. These voxels are about two orders of magnitude larger than the voxels used for proton imaging, but can be superimposed on proton MRI maps to permit reasonably accurate spatial identiﬁcation of the intraprostatic region supplying speciﬁc spectra. Spectral analysis relies on the fact that normal prostate tissue and the tissue of benign prostatic hypertrophy secrete relatively large amounts of citrate; prostate adenocarcinoma elaborates much less citrate, but produces a relatively elevated amount of choline; the ratios between the spectral peaks for these molecules are used to distinguish voxels containing neo- plasm from those that do not (123,124). Currently, the potential uses for magnetic resonance spectroscopic imaging (MRSI) of the prostate might be original diagnosis, biopsy guid- ance, local staging, and evaluation of recurrent following local therapy. With regard to diagnosis, several studies have shown that MRSI analy- sis of small groups of patients containing those without tumor and those with tumor can identify and localize tumors with reasonable, if less than perfect, sensitivity and speciﬁcity (125–128). But no sufﬁciently large or sufﬁciently well-controlled investigation has addressed whether MRSI is effective in screening for disease in a large sample reﬂecting either the pop- ulation at large or those at increased risk because of an elevated PSA. And given that many prostate tumors are considerably smaller than the MRSI voxels, it is unlikely that sensitivity can ever be very high until consider- able improvements in spatial resolution can be made. Series have been published to investigate whether patients whose prostate biopsies have been negative, even though their elevated PSA levels suggest tumor, might be aided by using MRSI to guide further attempts at biopsy. The data show that biopsies using information from MRI and MRSI converts some of these patients from being false negative (for the original biopsy) to true positive for the MR-guided biopsies, but there are few data to show that adding MRSI information to the MRI infor- mation is of signiﬁcant beneﬁt in guiding these biopsies (129). Further- more, the studies lack controls to investigate the possibility that the subsequent biopsies might have retrieved tumor tissue even without MR guidance. For patients who have had hormonal therapy (130) or who have had intraprostatic hemorrhage from a recent biopsy, localization of tumor by MRI can be difﬁcult; MRSI may permit tumor identiﬁcation in these cir- 130 J. Newhouse cumstances (131), however, so if MRI-guided biopsy ever becomes wide- spread, MRSI may be of beneﬁt. There are also series that investigate whether MRSI might improve the accuracy of MRI for prostate staging (130,132). In one, the addition of MRSI data to MRI data enabled inexperienced readers to become as accurate as experienced readers were with MRI alone, but, for experienced readers, MRSI data did not improve accuracy. However, MRSI may help in assess- ing overall tumor volume, which is also a factor in staging. But whether this information actually changes treatment decisions for the better has yet to be investigated. The feasibility of using MRSI to localize prostate cancer in aiding place- ment of radioactive seeds for brachytherapy and adjusting local doses for external beam therapy has been established (133,134). But whether this capacity actually improves outcomes, either in terms of disease control or complication reduction, is not yet known.
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