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Surveillance of Barretts Esophagus

Barrett's esophagus is usually discovered during endoscopic evaluation of patients who have symptoms caused by GERD or esophageal cancer. Studies suggest that in the general population, however, more than 90 of cases of Barrett's esophagus are not recognized, and many patients with the condition have few or no symptoms of GERD (Spechler, 1994). It is important to risk-stratify patients with GERD symptoms to determine who should undergo diagnostic upper endoscopy to effectively screen for Barrett's esophagus. Guidelines recommend that patients with longstanding GERD symptoms, especially but not exclusively white men over 50 years of age, undergo endoscopy at least once to screen for Barrett's esophagus (Sampliner, 2002). If Barrett's esophagus is not identified at the initial endoscopy, then further evaluation is not needed. Screening for Barrett's esophagns, however, remains a controversial issue. Adenocarcinoma develops in Barrett's esophagus by a multistep process in which...

Methods of Analyzing Gunshot Residues

By the mid-1980s, there were three generally accepted methods of analyzing for gunshot residues neutron activation, flameless atomic absorption spectrometry (FAAS), and scanning electron microscope-energy dispersive x-ray spectrometry (SEM-EDX). All threemethods werebasedonthedetection of metallic elements (principally barium, antimony, andlead)originatingin primers and deposited on the back of the hand firing the weapon. Although all three compounds were found in the primers of virtually all centerfire cartridges at that time, this was not necessarilythecasein rimfireprimers. Thus, until the mid-1980s, Remington rimfire cartridges contained only lead in their primers whereas they now containleadandbarium. CCIand Winchester rimfire ammunition contain lead and barium Federal, lead, barium, and antimony. Use of FAAS techniques for detection and quantitation of gunshot residues is very popular in crime laboratories in the United States because of a combination of ease of analysis,...

Wounds Due to Handguns

The Remington Firearms Company developed a method of measuring the performance of revolver ammunition that reflects ballistic results more accurately. This method involves use of a vented test barrel. The technique takes into account the cylinder gap (controlled at 0.008 in.), barrel length (4 in.), powder position (horizontal), and production tolerances, as well as allowing for reasonable wear and tear.1 Table 5.2 shows a comparison between the ballistic data that Remington previously published concerning its ammunition and the results obtained with a vented test barrel. Significant differences in the results can be seen.

Gunshot Wounds of the Brain

Gunshot wounds of the brain constitute approximately one-third of all fatal gunshot wounds. Wounds of the brain from centerfire rifles and shotguns are extremely devastating. Such injuries are described in Chapters 7 and 8. This section will deal with gunshot wounds of the brain caused by low-velocity weapons handguns and .22 rimfire rifles. When a bullet strikes the head, it punchesout acircular to oval woundof entrance in the skull, driving fragmentsof boneintothebrain. Thebone chips generally follow along the main bullet track, contributing toitsirregular configuration. Sometimes the bone chipscreatesecondary tracksthatdeviate from the main path. These chips are detectable on digital palpation in approximately one-third of gunshot wound cases of the brain.13 Use of high-resolution x-ray increases the percentage detected. The presence of bone chips at one end of the bullet track through the brain provides conclusive evidence of the direction of the shot in the author's experience,...

Suicide by Firearms

The most common method of committing suicide in the United States is by shooting. Approximately 65 of men committing suicide use firearms, with the remainder of the deaths almost equally divided between drug overdoses and hanging. Traditionally, the preferred method used by women was an overdose of drugs. Since the mid-1980s, however, use of firearms has become the most popular method of suicide in women.1 In 1970, in the United States, 30 of women shot themselves and 48 took an overdose of drugs by 1990, the percentages were 42 and 36 , respectively. In a study of 698 consecutive male suicides in San Antonio, Texas, 71.5 used a firearm, 13.8 hung themselves, 6.5 overdosed on drugs, and 8.2 used other means.2 Of 221 consecutive female suicides, 49.3 used firearms, 31.7 drugs, 10.4 hanging, and 8.6 other means. In regard to choice of weapons, handguns are used more often than rifles or shotguns. There is a difference in firearm use based on sex as demonstrated by the San Antonio study...

Detection of Gunshot Residues

In 1959, Harrison and Gilroy introducedaqualitative colormetric chemical test to detect the presence of barium, antimony, andleadonthehands of individuals who fired firearms. Thesemetals, whichoriginatefromthe primer of a cartridge on discharge of a weapon, are deposited on the back of the firing hand as discrete particulate matter (Figure 12.1). In revolvers these metallic particles come primarily from the cylinder-barrel gap, and in automatic pistols from the ejection port. The technique developed by Harrison and Gilroy was intended as a relatively simple inexpensive test for detection of these residues. In the test a square of white cotton cloth was moistened with hydrochloric acid and then used to swab the hand. The swab was treated with triphenylmethylarsonium iodide for the detection of

Accidental Deaths from Firearms

In order to decide whether a death from gunshot wound is an accident, one should know the circumstances leading up to and surrounding the death who was present, the findings at the scene, the type of weapon, the result of an examination of the weapon by a firearms examiner, the findings at autopsy, and the results of the toxicology study. The number of deaths in the U.S. from accidental gunshot wounds has steadily declined since 1970. In 1970, there were 2406 such cases in 1992, 1409.1 Even this number may be too high as suicides are not uncommonly labeled as accidents. This misclassification may result from a multitude of reasons lack of knowledge concerning weapons or the circumstances surrounding the death, naivete, an attempt to make things easier for a surviving spouse or family, etc. Misclassification of suicides as accidents is more common in coroner systems than medical examiner systems. It is the opinion of the author that, if an individual is holding a weapon and this weapon...

Wounds from Shotguns

Shotguns differ from rifles and handguns in construction, ammunition, ballistics, and use. Rifles and handguns fire a single projectile down a rifled barrel. Shotguns have a smooth bore. Although they can fire a single projectile, they are usually employed to fire multiple pellets. Rifled shotgun barrels, intended for use with slugs, are available. Shotguns may be autoloaders, pump (slide action), over unders, side-by-side, bolt action or single shot. Some shotguns intended for military and or police use convert from semiautomatic to pump action and back as the user desires. Barrel lengths of shotguns range from 18 to 36 inches with 26 and 28 in. the most common. Barrels 18 and 20 in. in length traditionally have been used only for police riot guns. With modern powders, barrel lengths greater than 18 and 20 in. produce only insignificant increases in velocity.1 Longer barrels are really just a matter of tradition, styling, balance, or a desire for a longer sighting radius. The usual...


Practical Aspects of Firearms, Ballistics, and Forensic Techniques OllklOIIAT Written by the nation's hIIN HII I foremost authority on fillH11O gunshot wounds and Ml Il II N IIX forensic techniques as they relate to firearm injuries, Gunshot second edition Wounds Practical Aspects of Firearms, Ballistics, and Forensic Techniques, Second Edition provides critical information on gunshot wounds and the weapons and ammunition used to inflict them. The book describes practical aspects of ballistics wound ballistics the classification of various wounds caused by handguns, rifles, and shotguns autopsy technique and procedure and laboratory analysis relating to weapons and gunshot evidence.

Barretts patients

Many studies have shown that the symptom expression in this group of patients is lower than in erosive GERD patients, as a manifestation of a reduced mucosal sensitivity to acid 26 , 27 . On the other hand, the presence of a specialized intestinal metaplasia in the distal esophageal mucosa is associated with a small but not negligible risk of developing adenocarcinoma 28 . In any case, the possibility that patients with Barrett's esophagus may subsequently develop adenocarcinoma is seriously considered by guidelines proposed by gastroenterological associations 29 , 30 , and therefore surveillance is recommended 31 , even if the cost-effectiveness of this recommendation is still debated 32 .

Zip Guns

The term zip gun as used in this bookindicateseither acrudehomemade firearm or a conversion of a blank pistol, tear gas gun, or cap pistol to a firearm.6 In the United States, zip guns had their peak of popularity in inner city areas during the juvenile gang wars of the 1950s. The quality of these weapons was extremely variable, with some so crude as to be a greater danger to the firer than to the intended victim. The simplest zip gun seen by the author was a metal tube in which a .22 Magnum cartridge was inserted. It was fired by striking the protruding base of the cartridge with a hammer. This weapon was used to commit suicide. The zip guns of the 1950s in the New York area generally were constructed of a block of wood, a car antenna (the barrel), a nail (the firing pin), and rubber bands (to propel the pin). Most of these weapons were chambered for the .22 rimfire cartridge. The chamber was generally oversized, resulting in bulging and splitting, i.e., bursting, of the fired case....

Stud Guns

Stud guns are industrial tools that usespecialblankcartridges tofiremetal nails or studs into wood, concrete, orsteel(Figure 10.2A). Theblankcar-tridges range in caliber from .22 to .38. Theyareloaded withfast-burning propellants that develop pressures toohighforafirearm to contain. Thus, they should never be used in firearms. Themouthof theseblankcartridges is sealed with a cardboard disk that is color-coded toindicatethestrength of the propellant. Stud guns have a built-in safety mechanismthat requiresaguardatthe end of the tool to be pressed firmly againstaflatsurfacebeforethe toolcan be fired. Workers have been known tousestudgunsfor plinking attin cans. They depress the safety guard with one hand and fire with the other. Stud guns have caused a number of accidentaldeathsatindustrialsites after the nails or studs have either perforated walls or ricocheted off a hard surface, striking and killing workers. In the cases in which a nail has ricocheted prior to penetrating the body,...

Barretts esophagus

The definition of Barrett's esophagus (BE), as discussed at a recent evidence based workshop, is based on a combination of endoscopic and histologic criteria consisting of an abnormal appearing distal esophageal lining (end-oscopic BE) with histologic evidence of intestinal metaplasia (confirmed BE). Barrett's esophagus has been arbitrarily divided into long (> 3 cm) and short segment (< 3 cm), although there is no evidence that a risk gradient for complications (i.e., dysplasia cancer risk) may be demarcated at a particular segment length 26 . The role of gastroesophageal reflux in the development of BE has been consistently shown in animal and human studies. In a rat model, BE could be induced in 80 of the animals following a jejunoesophageal loop. In a recent prospective study of 40 patients who underwent esophagogastrostomy and sub-total esophagectomy (done for adenocarcinoma or squamous cell carcinoma), 10 developed BE above the anastomosis 27 . Newer endoscopic techniques to...

Sawed Off Shotguns

Test firings, by the author, of sawed-off shotguns at ranges of 21 ft or less revealed that decreasing the barrel length of a cylinder-bore shotgun has no significant effect on the size of the pattern until the barrel has been sawed off to less than 9 in. At this point, the patterns begin to open up significantly. The author has seen a number of irrefutable cases of suicide, utilizing pump shotguns, in which death was instantaneous, yet the pump shotgun used to commit suicide was found to have an empty chamber and an ejected hull was present adjacent to the gun. These circumstances, understandably, aroused the suspicion of homicide. Examination of the shotgun in these cases, as well as other pump shotguns, revealed that they would eject the fired case after discharge if the slide was not restrained in a forward position. Other pump shotguns will unlock and only partially extract the fired case. If this latter weapon falls to the ground, landing on its butt, enough momentum may be...

Pathological Considerations

Types of columnar metaplasia are recognized. The commonest and clinically most important is intestinal metaplasia, and it is most likely to undergo malignant transformation to adenocarcinoma. The malignant potential of cardiac and fundic metaplasia is uncertain (24). The malignant degeneration within a segment of Barrett's esophagus occurs in a probabilistic rather than in an inevitably deterministic manner. Yet Barrett's does appear to be a necessary intermediary step, allowing interventional opportunities to stabilize the epithelium or destroy it. There is often a relatively long time sequence prior to the development of cancer. This may allow early intervention with endoscopic ablation, chemo, or surgical prophylaxis. Pathological diagnosis is dependent on the endoscopist clearly identifying the site of biopsy in the gastric cardia, a hiatus hernia, or in the esophagus. The endoscopic problem is that the anatomy and position of the gastroesophageal junction is difficult to define....

Rationale And Criteria For Consideration Of Ablation Treatment

At what stage should consideration be given to the ablation of the Barrett's epithelium This is a subject of much debate, but, generally, intervention is considered following the diagnosis of dysplasia. The pathological difficulties make radical therapy at the time of diagnosis of dyspla-sia difficult. Initially, the diagnosis of high-grade dysplasia should be confirmed by further biopsies and a second, preferably expert, pathologist. The natural history of dysplasia remains uncertain, with contradictory and confusing data. There are arguments for rigorous-protocol endoscopic surveillance of patients with high-grade dysplasia with jumbo biopsy and intervention at the diagnosis of cancer (33). Recently, a very large study has demonstrated a cumulative cancer incidence over five years of only 9 , with only 12 of 75 (16 ) of patients developing cancer during 13.9 years of surveillance. This U.S. group adopted a very aggressive approach to the diagnosis of synchronous cancer with...

Theoretical And Practical Considerations For Endoscopic Mucosal Ablation

There are important considerations in the choice of endoscopic mucosal ablation. The most important being the depth of destruction that can be obtained to destroy both Barrett's mucosa and neoplastic tissue and, at the same time, allow safe healing. The mean thickness of nondys-plastic Barrett's mucosa is about 0.6 mm. This figure has been derived by measurement in various ways. Histopathology measured Barrett's mucosa to be 0.5 mm (range 0.39-0.59 mm) compared with a normal squamous epithelium of 0.49 (range 0.42-0.58 mm) (36). It was assumed that fixation produces a 10 shrinkage with a further 10 reduction which was caused by processing producing a shrinkage of 20 . Thus, the mean thickness of Barrett's mucosa is approximately 0.6 mm. Optical coherence tomography (OCT) of excised unfixed specimens has recorded a depth of between 0.45 mm and 0.5 mm (37). Dysplasia and mucosal cancer are thicker and in OCT appear optically denser. This represents approximately 15 of the thickness of...

Initial Clinical Trials

There has been a randomized partially blinded trial for prevention of cancer in Barrett's esophagus, which examined 208 patients with confirmed high-grade dysplasia. It is very instructive to note that over 485 patients (with a diagnosis of high-grade dysplasia) had to be screened to enter 208 patients with confirmed high-grade dysplasia. The patients were randomized (2 1) such that 138 had PDT and omeprazole (O) and 70 received omeprazole only. At the end of the minimum of 24-month follow-up, ablation of all areas of high-grade dysplasia was noted in 76.8 of patients in the PDT + O group (n 138) versus 38.6 in the O group (n 70) (P < 0.0001). After a mean follow-up of 24.2 months, 13.0 of patients in the PDT + O group had disease progression to cancer as compared to 28 in the O group after a mean follow-up of 18.6 months (P 0.006). Strictures occurred in 37.1 of patients following PDT (67). This preliminary data establishes that PDT is now a highly effective treatment for the...

Bloody Bodies and Bloody Scenes

Physical Activity Following Gunshot Wounds Wounds Seen in the Emergency Room Minimal Velocities Necessary to Perforate Skin Bullet Emboli Gunshot Wounds of the Brain Bone Chips Secondary Fractures of the Skull Shape of the Bullet Tracks Point of Lodgement of the Bullet Intrauterine Gunshot Wounds Lead Poisoning from Retained Bullets Location of Fatal Gunshot Wounds Behavior of Ammunition and Gunpowder in Fires Blunt-Force Injuries from Firearms Multiple Gunshot Wounds Through One Entrance Falling Bullets

Theoretical Issues

While demography has begun to wrestle with the larger meanings of gender and its broader relationships with demographic behavior, it is particularly from the perspective of theory that we can best see the gaps in our knowledge on these issues and some of the reasons why these gaps remain. The best way to recognize potential contributions to understanding gender's role in demographic change is to step back from demography, look at what is happening and is being discussed about gender in other social sciences, and then see how those insights and perspectives might be used in demography.4 Theory holds a very important place in gender studies. Theory has been central to the growth and depth of gender studies over the last couple decades. Work has focused both on critiquing and '' 'destabilizing ' the founding assumptions of modern theory'' (Barrett and Phillips 1992 1) and creating new theory that speaks to the role of women, men, and gender in the social world (see Evans 1997 Barrett and...

The influence of humans

Humans have had a profound negative impact on the distribution of the world's mammals, through hunting, habitat destruction, and introductions. The consequences of hunting may have begun with early humans, as the Columbian mammoth (Mammuthus columbi) went extinct after only 500 years of contact with Clovis humans. Many of the large mammals of the Mediterranean coasts of North Africa were exterminated by the Romans who exported huge numbers of them to Rome to be killed in public arenas. The invention of modern firearms drastically increased the destructive potential of hunting. An estimated 60 million bison (Bison bison) existed across North America at the beginning of the eighteenth century but 150 years later they had been hunted to the brink of extinction and their former distribution reduced to fragments. During the nineteenth and twentieth centuries Arabian oryx (Oryx leucoryx) and gazelles were severely depleted in Arabia and North Africa, and the tiger (Panthera tigris)...

Homoplasy the fundamental problem

The reckoning of two separate data sets (Figure 2.9) produces separate analyses for two individual data sets, and a consensus tree might be the minimal representation of evolutionary relationships supported by the evidence. A consensus tree extracts the parts of two other trees that are in agreement, even if they may present some apparent contradictions (Adams 1972 Swofford 1991). Consensus trees inevitably produce degradation of bifurcating nodes to multifurcations, or stars. This is not an improvement so much as an admission of uncertainty. Cases have been found (Figure 2.9), moreover, in which the total data set produces more resolution and a tree that is clearly more informative and correct than the consensus of two trees representing different data types (Barrett et al. 1991 Eernisse and Kluge 1993). Whether this can be generalized to larger numbers of informative characters is unclear.

Fusarium Crown and Root

Fusarium crown and root rot (Frl) caused by the pathogen Fusarium oxysporum f. sp. radidicis-lycopersici, is often found in European greenhouses, but can also be found in locations with cool weather. Infected plants wilt similarly to those infected with fusarium wilt, but vascular browning is found only in the crown of the plant. Resistance is controlled by a single dominant gene, Frl (Berry and Oakes 1987 Vakalounakis 1988) derived from S. peruvianum and mapped to chromosome 9 (Vakalounakis 1997). Researchers selecting for the Tm22 gene found linkage to fusarium crown rot resistance (Laterrot and Couteadier 1989 Laterrot and Moretti 1992, 1996).

Goals Strategies And Societys Options

The prevailing, though not hegemonic, view is that mental health services for the old, as for other age groups, have as their primary obligation the treatment of mental illness and, to some extent, ''problems in living,'' however defined. Despite this bias, strong arguments for the more expansive view are readily available. For example, Browning (1991) observes (Browning, 1991, p. 7). These images, as the historical review has suggested, are necessarily value laden. It is possible, however, to face these value dimensions openly. If psychiatry does not do so, it has little recourse except retreat to the biomedical model and its reductionist views. A biological conceptualization of mental illness can, as observed earlier, result in the psychological abandonment of patients who face situational problems.

Wound Ballistics of the Shotgun

In rifled weapons, the weight of the bullet does not change no matter how great the distance. In contrast, in shotguns, as the range increases there is dispersion of shot with resultant decrease in the number of pellets that strike the target. Although velocity decreases with range in rifled weapons, this decrease is very little at the short ranges at which most killings occur. In contrast, the unfavorable ballistic shape of the shotgun pellet, combined with the lack of stabilizing spin, causes a rapid fall-off in velocity such that beyond a relatively close range, pellets have insufficient velocity to perforate skin. Thus, unlike rifled weapons, in shotguns, the range from muzzle to target is extremely important in determining the number of pellets that strike a body and enter it.

Significance to humans

Cane rats can be a pest by causing great damage to vegetable gardens and crops. The meat of the cane rat is tasty and is widely utilized in African countries. Cane rat meat is much in demand, and they are often hunted in organized drives with spears, dogs, and firearms. In West Africa, people have traditionally captured cane rats in the wild and raised them at home. As an off-spin of this, some farmers have initiated organized cane rat husbandry. Because the meat is considered excellent and a huge market for the meat exists, some farmers in South Africa are showing an interest in farming these animals as micro-livestock.

Miscellaneous Shotgun Ammunition

The Remington Modi-Pac refers to the Modified Impact Shotgun Shell. This round, which apparently was produced in the late 1960s, used an SP tube with a rolled crimp. It was intended by law enforcement agencies for riot control. Only 12-gauge shells were manufactured these shells contain 1 4 oz of 0.120-in.-diameter plastic pellets. Approximately 320 pellets per load were used. The muzzle velocity was 1600 ft sec. Loss of velocity was extremely rapid because of light weight of the pellets. Thus, at 15 yd, muzzle velocity was only 200 ft sec. Maximum range was 25 yds. Given the low pressure generated in these shells, they would not function in auto-loading shotguns.

Fibulins notch signalling and cancer invasion

Et al. (1997) described LOH of I4q31-32.1 in human head and neck squamous cell carcinomas. They found frequent LOH at that locus, and specifically the loss of 4-7 cM regions of I4q31-32.1. But Bockmuhl et al. (2000) encountered over-representation of I4q31 and I4q32, among other loci. In both studies, the genetic alterations were associated with reduced patient survival. Cheng et al. (1997) reported LOH at I4q31 locus in 7 21 nasopharyngeal carcinomas that they had investigated. LOH was frequently encountered in adenocarcinoma of the oesophagus and gastric cardia, and interestingly LOH occurred more frequently in adenocarcinomas of Barrett's oesophagus than of gastric cardia (Van Dekken et al., 1999). In most of these studies genetic changes occurred also in other chromosomes, and as a consequence it is difficult to evaluate the contribution of changes at the I4q31 locus to the pathogenesis of the disease. Recently Chiaramonte, Calzavara et al. (2002a) failed to notice any genetic...

Key Concepts In Urban Health

Third, cities have unique assets and problems. For example, cities use energy more efficiently, tolerate better differences in values and behavior, and have a richer array of health, social service and community-based organizations than rural or suburban communities. For some health conditions and in some places, urban residents are healthier than their non-urban counter-parts. But cities also have higher rates of many illnesses, more access to health-damaging resources (e.g., drugs and guns), and higher levels of the income disparities associated with poor health. To be effective, urban health professionals need the tools to identify these unique strengths and weaknesses and the skills to use the assets to address the problems.

Attitudes toward Crime

The extensive publicity given to crime by the media has undoubtedly contributed to the American public's fears and concerns about crime. Americans consider crime to be the nation's most serious problem. Thus, Gallup polls conducted in 1993 and 1994 found that 87 of both the white and black respondents believed that crime is on the rise, and 25 were deeply afraid of it (Gallup, 1996 McAneny, 1993). Furthermore, 80 of the persons in a representative sample polled by Moore (1994) indicated that they favored the death penalty for adults and 60 for juveniles who committed murder. Despite their fears concerning crime, the majority of residents of the United States who were questioned in McAneny's (1993) poll indicated that they took no special precautions to cope with it. Still, slightly over 40 of all people in this country report owning guns, a rate that is highest in the 18-20 age group (U.S. Department of Justice, 1994).

Immunostimulant And Immunomodulator

The immunostimulant activity of echinacea has been the subject of countless studies. Overall, the fresh-pressed leaf juice of E. purpurea and alcoholic extracts of the roots of E. pallida, E. angustlfolla and E. purpurea have been shown to act mainly on nonspecific cellular immunity (Blumenthal et al 2000). Macrophage activation has been well demonstrated, as has stimulation of phagocytosis (Barrett 2003, Bauer et al 1988). Orally administered root extracts of echinacea have produced stronger effects on phagocytosis than aerial parts, with E. purpurea roots producing the greatest effect, followed by that of E. angustlfolla and E. pallida (Pizzorno & Murray 2006).

Diagnosis and Histopathology

The diagnosis of Barrett's esophagus requires biopsy of the endoscopically abnormal-appearing esophageal mucosa to document intestinal metaplasia. The more biopsies taken and the greater the length of the Barrett's segment, the greater the chance of recognizing intestinal metaplasia. Specialized intestinal metaplasia with goblet cells in biopsy specimens from endoscopically salmon-colored esophageal mucosa is diagnostic of Barrett's esophagus. Biopsy is also essential to exclude dysplasia, the earliest neoplastic change in the mucosa. Both short-segment and longsegment Barrett's esophagus are associated with an increased risk of dysplasia and cancer, and the cancer risk in patients with short-segment Barrett's esophagus is believed to be similar to the risk in patients with long-segment Barrett's esophagus (Spechler, 1997 Falk, 2001). In patients with Barrett's esophagus, biopsies are not routinely performed from areas of esophagitis because of the difficulty of excluding dysplasia...

Range Determination in Decomposed Bodies

Determination as to whether a gunshot wound in a decomposing body is either close-range or distant can be difficult for a number of reasons. First are the changes of decomposition itself. Decomposition results in a blackish discoloration of the skin and subcutaneous tissue, which can either simulate or conceal soot. There is slippage of the epidermis, which can produce In addition to the changes of decomposition, insect activity can obliterate as well as simulate wounds. Maggots and beetles are attracted to injury sites where blood is present. They can completely obliterate the entrance in the skin and thus any evidence of soot or powder. Insects can burrow into the skin, producing circular defects resembling gunshot entrance wounds. If there is subsequent drying of the edges, this may simulate the blackening and searing of a contact wound from a small caliber weapon (Figure 12.6). In contact wounds from shotguns and rifles, only lead may be detected by EDX at the wound entrance. The...

Classes Of Saccharomyces Cloning Plasmid Vectors

A typical Saccharomyces transformation is carried out as follows. An appropriate host vector pair is selected. For example, a host strain carrying the ura3-52 allele is unable to grow on a minimal medium that lacks uracil because it is unable to synthesize uracil, which is essential for various cellular processes including RNA synthesis. If a plasmid carrying the wild-type dominant URA3 gene is introduced into this host strain by transformation, then the transformant will be able to grow on a minimal medium lacking uracil. The plasmid DNA is transformed into the host cells by any one of a number of methods including chemical treatments, electro-poration, or pellet guns. The DNA treated cells are plated on a solid synthetic medium lacking uracil. Only those individuals that have acquired a stable copy of URA3 by transformation with the plasmid vector will be able to form colonies. Of course this must be confirmed by appropriate tests.

Methodological Issues

It is tempting to speculate on the mental health of those who decline to participate in research. Some would argue that these individuals have coped well and are reluctant to invest time and energy into something for which they feel no need. Others would argue an opposing view and suggest these individuals are not coping well and feel too distressed. The situation is further complicated by the suggestion that the decision whether or not to participate in bereavement research may be gender related (Stroebe & Stroebe, 1989). A different rate of recruitment or attrition between groups adds to the dilemma in identifying the effects of different interventions. A third of participants in one study dropped out after finding out to which one of four groups they had been allocated (Barrett, 1978, cited in Kato & Mann, 1999). People may choose the intervention with which they feel most

Lower esophageal sphincter

Phrenoesophageal Membrane

Anatomy of the diaphragmatic hiatus. The right crus makes up the muscular component of the crural diaphragm. Arising from the anterior longitudinal ligament overlying the lumbar vertebrae. A single muscle band splits into an anterior and posterior muscular band, which cross each other to form the walls of the hiatal canal and then fuse anteriorly. With hiatus hernia the muscle becomes thin and atrophic limiting its ability to function as a sphincter. ( 53 Pandolfino JE, Kahrilas PJ (2001) Esophageal motility abnormalities in Barrett's esophagus. In Barrett's esophagus and esophageal adenocarcinoma (Sharma P, Sampliner RE, eds). Malden Blackwell Science, pp 35-44, with permission) Fig. 2. Anatomy of the diaphragmatic hiatus. The right crus makes up the muscular component of the crural diaphragm. Arising from the anterior longitudinal ligament overlying the lumbar vertebrae. A single muscle band splits into an anterior and posterior muscular band, which cross each other to form...

Gastrointestinal Specimens

ABC of liver, pancreas and gall bladder diseases. London BMJ Books, 2001 Biddlestone LR, Bailey TA, Whittles CE, Shepherd NA. The clinical and molecular pathology of Barrett's oesophagus. In Kirkham N, Lemoine NR (eds). Progress in pathology 5. London Medical Media Limited. 2001 57-80

Methylene Blue Dye Color Variation Esophageal Cancer

Conventional endoscopy with or without a barium swallow is usually performed as an initial assessment of the primary tumor to enable a tissue diagnosis. More recently, highresolution endoscopy has been performed for early esophageal lesions with chromoendoscopy using methylene blue dye for known cases of Barrett's esophagus and Lugol's iodine where squamous-cell carcinomas are common (10). The accuracy of high-resolution endoscopy in the diagnosis of superficial esophageal lesions is in the region of 80 (10).

Analytical Examination of Clothing for Range Determination

The Modified Greiss test is the evolutionary end product of the Walker test. This latter test was developed to detect nitrite compounds produced by the burning of smokeless powder (cellulose nitrate). The Walker test documents the presence of nitrites as well as showing the size, configuration and density of the pattern on clothing or other objects. A firearms examiner can then attempt to duplicate this pattern by firing the same weapon and type of ammunition, at know distances, at the same type of material. This procedure will give the examiner an approximation of the range at which the individual The Sodium Rhodizonate test, long used as a spot test for lead and barium, constituted one portion of the Harrison and Gilroy test for the detection of gunshot residue on the hands.2 It is now used by firearms examiners for the detection of lead residue around an entrance.13 This lead is principally from the primer though some of it originates from the bullet and lead residue deposited in...

Culture Bound Syndromes Cultural Variations and Psychopathology

Inaccuracies in the assessment and diagnosis of psychopathological conditions with culturally diverse groups (i.e., overdiagnosis, underdiagnosis, and misdiagnosis) might result from a lack of understanding of the presence of cultural variants leading to symptoms resembling psychopathology. These variables have generally been described in the case of culture-specific disorders known as culture-bound syndromes (Castillo, 1997 Dana, 1993 Dana, 1995 Ivey, Ivey, & Simek-Morgan, 1996 Paniagua, 1998 Pedersen, 1997 Pedersen, Dra-guns, Lonner, & Timble, 1996 Ponterotto, Casas, Suzuki, & Alexander, 1995 Smart & Smart, 1997). Smart and Smart (1997), for example, pointed out that the glossary (Appendix I) of culture-bound syndromes included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV American Psychiatric Association, 1994) are description of 25 forms of aberrant behavior that are referred to as locality-specific troubling experiences that are limited to...

Investigations of specific cancers Bowel cancer

Among the larger studies, a further study in the North of England and Scotland found no evidence of variation in risk attributable either to the NAT1 or NAT2 polymorphisms or to meat intake (Barrett et al., 2003). In a case-control study conducted in the USA, the amount of red and white meat consumed was not associated with overall colon cancer risk (Kampman etal., 1999). Processed meat

Social Anxiety In Children And Adolescents

Because one of the hypothesized mechanisms of transmission for anxiety is observational learning and modelling within the family (Bruch, 1989 Bruch & Heimberg, 1994), additional involvement of the family in treatment may add to the efficacy of CBT. Barrett, Dadds & Rapee (1996) examined the efficacy of Kendall's intervention, alone or in combination with family anxiety management treatment (FAM), for 79 children with separation anxiety, overanxious disorder, or social anxiety disorder. FAM comprises strategies to support and encourage adaptive behaviour and to extinguish maladaptive behaviour, a component for the management of parental anxiety and training in problem-solving skills to extend the child's progress in treatment. The combined treatment was superior to child treatment alone on several clinical and self-report measures after treatment and at 12-month follow-up. Again, no differential response based on diagnosis was noted.

Interchangeability of Ammunition in Weapons

Ruger manufactures a line of single-shot revolvers that have interchangeable cylinders. Thus, one weapon will fire .38 Special and .357 Magnum ammunition in one cylinder and 9-mm Luger in another interchangeable cylinder. Another weapon fires .45 ACP in one cylinder and .45 Colt in a second. A number of firearms companies manufacture .22 rimfire revolvers with two interchangeable cylinders one for .22 Short, Long, and Long Rifle cartridges and the other for the .22 Magnum cartridge.

Therapies Targeting the Immune System

The incidence of autoimmune disorders is increased in some MDS populations (Saif et al. 2002). Autologous cy-totoxic T-lymphocytes have been observed to exert an inhibitory effect on MDS myelopoiesis in vitro. The clinical features of subsets of MDS overlap with aplastic anemia (AA) and large granular lymphocyte (LGL) lym-phoproliferative disorders, two diseases thought to be related to dysregulation of the immune system (Barrett et al. 2000). Clinical studies have shown activity of the immunosuppressives antithymocyte globulin and cy-closporine in the treatment of select groups of MDS patients.

The role of cagApositivestrains in patients with oesophageal adenocarcinoma

Quddus et al did not find any Helicobacter pylori infected in 19 patients with Barrett's adenocarcinoma 60 . In a larger study population Helicobacter pylori again has been identified in significantly higher proportion of patients with benign Barrett's oesophagus than in those with dysplastic Barrett's oesophagus or Barrett's adenocarcinoma (34 vs. 17 ) 61 . A multicenter study did not find a difference in the prevalence of Helicobacter pylori infection in patients with oesophageal adenocarcinoma when compared to age- and sex-matched controls. However infection with the cagA+ strain of the bacteria resulted in a reduced odds ratio for developing oesophageal adenocarcinoma 57 . These results have been confirmed in a smaller study by Vicari et al 5 and may be explained by Helicobacter pylori induced apoptosis in Barrett derived oesophageal adenocarcinoma cells which is mainly dependent on the presence of the cagA and picB cagE gene products 62 .

Psychological Practice Determining Individual Capacity to Participate in Mediation

Part One of this Handbook reviews in considerable detail the contributions of psychology to the legal system, describing how clinicians may provide both quantitative and qualitative information about individuals in a range of adjudicative contexts. For the purposes of the present chapter, it suffices to observe that a properly conducted forensic psychological examination of the constructs described supra will include not only cognitive and personality assessment via testing (Camara, Nathan and Puente, 2000 Meyer etal., 2001), but also specific attention to several supplementary sources of information. Many of these sources will have been identified in the course of the criminal investigation leading to the offender's current conviction. Relevant data will be produced from review of legal, treatment, military, forensic, and other records interviews with teachers, family, friends, law enforcement personnel, and other parties and consultation with legal counsel and other professional...

Incidence and prevalence of esophagitis

Hed in 1993 an important paper dealing with the incidence of RE they examined al the reports of upper GI endoscopy performed in patients aged > 16 years and living in a defined catchment area of 226,776 inhabitants during a 2-year period. The incidence of RE was calculated to be 120 per 100,000 in 88 it was a simple, uncomplicated, erosive esophagitis. The incidence of complicated RE and of Barrett's esophagus was 5.6 and 1.7 per 100,000, respectively 34 . In this study, the severity of esophagitis significantly increased with age (p 0.003) and most (75 ) of the patients with complicated esophagitis were > 60 years of age. Men had more severe grades of esophagitis than women (p 0.003).

Uses And Interpretation Of Data

The transformation of primary Syrian hamster embryo (SHE) cells in vitro has been shown to be a useful tool for the identification of both genotoxic and non-genotoxic rodent carcinogens (71). One way to help determine whether a positive response in the SHE cell transformation assay is caused by a genotoxic or non-genotoxic mechanism is to measure micronucleus induction in SHE cells. As reviewed by Tsutsui and Barrett (72), an assessment of micronuclei in SHE cells treated with various estrogens has been useful in understanding the role of geno-toxicity, particularly aneuploidy, in the transforming ability of these compounds. Gibson et al (73) reported a good agreement between the SHE cell micronucleus assay and SHE cell transformation assay for mutagenic chemicals, but a number of chemicals were negative in the SHE micronucleus assay that induced cell transformation, as would be expected because transformation can occur via a nongenotoxic mechanism.

Suggested Readings

Barrett's oesophagus a review of costs of the illness. Pharmacoeconomics 2001 19 1003-1011. Barrett MT, Sanchez CA, Prevo LJ, et al. Evolution of neoplastic cell lineages in Barrett oesophagus. Nat Genet 1999 22 106-109. Benipal P, Garewal HS, Sampliner RE, et al. Short segment Barrett's esophagus relationship of age with extent of intestinal metaplasia. Am J Gastroenterol 2001 96 3084-3088. Buttar NS, Wang KK, Anderson MA, et al. The effect of selective cyclooxygenase-2 inhibition in Barrett's esophagus epithelium an in vitro study. J Natl Cancer Inst 2002a 94 422-429. Buttar NS, Wang KK, Leontovich O, et al. Chemoprevention of esophageal adenocarcinoma by COX-2 inhibitors in an animal model of Barrett's esophagus. Gastroenterology 2002b 122 1101-1112. Buttar NS, Wang KK, Lutzke LS, Krishnadath KK, Anderson MA. Combined endo-scopic mucosal resection and photodynamic therapy for esophageal neoplasia within Barrett's esophagus. Gastrointest Endosc 2001a 54...

Suicides Due to Long Arms

In suicides with long arms (rifles and shotguns), just as with handguns, the preferred sites are the head, chest, and abdomen, in that order. There is, however, very little difference in the percentage of head wounds between the sexes (Table 14.2). Thus, 69 of the men and 65 of the women had entrance wounds of the head.3 The percentage of people shooting themselves in the head with rifles and shotguns is not as great as with handguns. This may be due to the fearsome reputation of these weapons. People do not mind shooting themselves in the head but do not want to blow their head off. In deaths involving centerfire rifles, most wounds of the head are in the mouth or temple. A study of 46 suicidal centerfire rifle wounds of the head revealed the location of the entrance, in decreasing frequency, was the mouth (41.3 ), the temple (26.1 ), underside of the chin (15.2 ), the forehead (13 ), and other (4.4 ).2 A study of 89 contact shotgun wounds of the head by Harruff found a similar...

Diagnosis Of Boron Status In Plants

Boron deficiency results in longitudinal splitting of roots (75). Boron-deficient carrot roots are rough, small with a distinct white core in the center and plants show a browning of the tops (71). Cauliflower (Brassica oleracea var. botrytis L.). The chief symptoms are the tardy production of small heads, which display brown, waterlogged patches, the vertical cracking of the stems, and rotting of the core (74) (Figure 8.2). When browning is severe, the outer and the inner portions of the head have a bitter flavor (76). Stems are stiff, with hollow cores, and curd formation is delayed (77). The roots are rough and dwarfed lesions appear in the pith, and a loose curd is produced (69). Barley (Hordeum vulgare L.). Boron toxicity is characterized by elongated, dark-brown blotches at the tips of older leaves (79). Severe browning, spotting, and burning of older leaf tips occur, gradually extending to the middle portion of the leaf (59,63). There is a reduced...

Organ Systems Affected By Low T Levels

Cognitive function decreases with aging. Most of the age-related changes in cognition are associated with vascular and or degenerative diseases that cause anatomic changes in the central nervous system. The possibility that an age-related fall in T causes functional changes in cognition is of great interest. In a study involving 407 men aged 50 to 91 years at baseline and followed for an average of 10 years, Moffat and colleagues showed that higher free T indices were associated with better scores on visual and verbal memory, visuospatial functioning, and visuomotor scanning, and a reduced rate of decline in visual memory (Moffat et al., 2002). On the other hand, men classified as hypogonadal had significantly lower scores on measures of memory and visuospatial performance and a faster decline in visual memory. Of course, changes in the CNS could cause hypogonadism rather than be caused by hypogonadism. In another study by Barrett-Conner and associates, low...

Effect of Helicobacter pylori eradication on GORD symptoms and severity

The first report of Labenz et al on an increase of the incidence of oesophagitis in ulcer patients after Helicobacter pylori eradication has been confirmed by further studies in patients with corpus predominant gastritis and associated hypochlorhydria. The effect was attributed to the recovery of acid secretion after Helicobacter pylori eradication 15 , 16 . Further studies confirmed the increase of gastro-oesophageal reflux 17 , 18 after eradication. A recent prospective, double blind, placebo controlled, randomised trial including 104 Helicobacter pylori infected GORD patients could show that Helicobacter pylori eradication was the only predictor of treatment failure of GORD. The authors explained the worsening control of reflux disease after Helicobacter pylori eradication with the ammonia production of Helicobacter pylori infection which augments the acid suppressing effect of medication. After successful eradication rebound acid secretion on reduced dosage of PPI may have caused...

Clinical Spectrum Natural History And Epidemiology Of Gerd

GERD is a spectrum disease, i.e., a disease composed by many patient subgroups, ranging from symptomatic disease without mucosal lesions (or NERD) to the complications of erosive esophagitis, such as esophageal stricture, ulceration or Barrett's esophagus. Almost all the transitions are possible amongst groups, even if the progression from one stage to the other has been described mainly based upon retrospective data. The principal complication, e.g., Barrett's esophagus, has a prevalence of 15-20 of the GERD population, with a rate of adenocarcinoma development of about 0.5 per patient year of follow up. Mortality for uncomplicated GERD is negligible. (Fig. 3). The latter schematization does in fact represent a new conceptual framework, in that it categorize GERD patients into 3 unique groups of patients non-erosive reflux disease, erosive esophagitis and Barrett's esophagus we disagree with this model, for various reasons, but basically we think that the principal conceptual mistake...

Incidence and prevalence of GERD symptoms

Finally, there is robust evidence that symptom severity is a poor predictor of severity of mucosal damage 36 , whereas at least the frequency of symptoms seems to be related to the amount of esophageal acid exposure 46 . Thus, the presence or absence of esophagits, as well as the presence of Barrett's esophagus might not be predicted by the patient'symptom profile, and therefore endoscopic diagnosis is still essential to reliably assess these conditions 47 .

Utility of endoscopy in addition to confirmation of diagnosis

An additional benefit of endoscopy in GERD patients is that it provides the opportunity for therapeutic stricture dilation, as well as biopsy confirmation of any tumors or Barrett esophagus. It can also identify the subset of patients who may need future surveillance, although this is controversial. An index endoscopy for GERD may also obviate need for future screening procedures as BE is almost always diagnosed at its full extent at the first endoscopy 64 and rarely, if ever, develops after a normal endoscopy. Therefore, those who respond to a treatment trial and have no erosive esophagitis or BE on the initial endoscopy would be able to enter a maintenance treatment program with no further fears of significant pathology.

Direct Effects of

It is estimated that, on average, guns, bombs, mines and chemicals kill 0.2 million children and disable 0.5 million children every year (Machel, 2000). In addition, at any given time, 300,000 children less than 18 years of age are fighting as soldiers (Machel, 2000) - many are forced to fight against their will, and many are brutalized and tortured.

Intentional and Unintentional Injury

A study by Sorenson and Shen (1996a) found that immigrants were overrepre-sented among the homicide deaths of 64,510 Californians during the years 1970 through 1992. Although immigrants comprised an estimated 17.4 of California's population during these years, they accounted for almost one-quarter of the state's homicide victims. The researchers found that non-latino white immigrants were 1.66 times as likely to die due to homicide as non-latino whites born in the U.S., while black immigrants were less likely than U.S.-born blacks to die due to homicide. Shen and Sorenson (1998) hypothesized that the increased risk of homicide among non-latino whites may be attributable to an increase in exposure, since many come from European countries that regulate access to firearms more strictly than does the U.S.

Personality Disorders A Paranoid Personality Disorder

Behaviors influenced by sociocultural contexts or specific life circumstances may be erroneously labeled paranoid. For example, immigrants, political and economic refugees, and members of minority groups may show guarded or defensive behaviors because of either unfamiliarity with the language, rules and regulations in the United States, or because of the perceived neglect or indifference of the majority society (DSM-IV 1994, p. 636). Castillo (1997) provided further illustration of this disorder in cultural terms in the case of men in Swat Pukhtun society (tribal people living in the mountains of northern Pakistan). All males in this society own guns and they trust no one and are constantly vigilant in protecting their honor and their personal interests. Pukhtun men distrust the sexual loyalty of all women to the extent of keeping them confined in their homes (Castillo, 1997, p. 99). As noted by Castillo (1997), these behavioral patterns among Pukhtun men are examples of normative...

Neoplastic Conditions

Oesophageal carcinoma predisposing conditions to oesophageal cancer include diverticula, achalasia and Plummer-Vinson syndrome (elderly females, iron-deficiency anaemia, upper oesophageal web). Predisposing lesions to oesophageal cancer are squamous cell dysplasia and Barrett's metaplasia dysplasia. Barrett's metaplasia or columnar epithelium lined lower oesophagus (CLO) seen in about 10 of patients with hiatus hernia and or GOR. It arises from erosion with differentiation of multipotential stem cells to metaplastic small intestinal or gastric glandular epithelia. The Barrett's segment appears as a velvety area proximal to the OG junction surrounded by pale squamous mucosa. It can be multifocal or continuous. The segment is either classical long (> 3 cm), short (< 3 cm ), or ultra-short (junctional). About 10 of Barrett's cases develop mucosal dysplasia and or adenocarcinoma, representing an increased risk of 30-40 times that of the general population. Barrett's metaplasia...

Discharge of a Weapon

Now that we have attained a basic knowledge of firearms and ammunition, let us consider the sequence of events that occurs when one brings the two elements together. Pulling the trigger causes release of the firing pin. This strikes the primer, crushing it, igniting the primer composition, and producing an intense flame. The flame enters the main chamber of the cartridge case through one or more vents, igniting the powder and producing a large quantity of gas and heat. This gas, which may be heated to 5200 F, exerts pressure on the base of the bullet and sides of the cartridge case, which varies In revolvers, in addition to the gas, soot, vaporized metals, and powder particles emerging from the muzzle of the weapon, similar material emerges from the cylinder-barrel gap (Figure 2.11). If the cylinder of the weapon is not in perfect alignment with the barrel, fragments of lead will be avulsed from the bullet as it enters the barrel and will also emerge from this gap. In revolvers made...

Captive Bolt Devices Pistols

The end of the bolt is usually circular, 7 to 12 mm in diameter, with sharp edges. It produces a sharp-edged, circular hole in the skin and bone, whose diameter is slightly less than that of the bolt. In contact or near-contact wounds, the wound in the skin may be surrounded by either two or four symmetrically arranged deposits of soot produced by gas escaping from openings (2 or 4) at the end of the muzzle. These act as vents for the gas produced by the blank. The deposits of soot decrease in intensity, finally disappearing, as the range increases. Not all guns have vents at the muzzle, however.

Methodological Issues And Potential Moderated Relationships

Although we still speak of content, construct, and criterion-related validation (Binning & Barrett, 1989), it is now recognized that there are no different types of validity, only different strategies for justifying inferences (SIOP, 1987) and different inferences that might be justified (e.g., statistical conclusions vs. construct-related conclusions Cook & Campbell, 1979). Validation involves theory development and testing, and any information about the test or job in question can contribute to a basis for conclusions regarding test scores (Binning & Barrett, 1989).

Mechanisms of hearing impairment

Cochlea Cross Section

Loss at the basal end of the cochlear duct (the region normally involved in high frequency detection). The second type was strial presbyacusis, with more equal hearing loss across the frequency range and atrophy of the stria vascularis, a structure on the lateral wall of the cochlear duct that pumps high levels of potassium into the fluid bathing the upper surface of the hair cells and generates a high resting potential in this fluid. A third type, neural presbyacusis, was rare but showed loss of cochlear neurons leading to limited threshold increases but difficulty in speech discrimination. This is a useful first step in grouping pathological mechanisms. However, as we discover more of the genes underlying hearing impairment (see later), and understand more about their involvement in the pathological process, it is becoming clear that there are dozens, maybe hundreds, of different ways that hearing can be compromised. Furthermore, other parts of the auditory system can be involved in...

The Nature Of Performance

Until 10 or 15 years ago, I O psychology had a tendency to focus on predictors of performance to the exclusion of performance itself, in spite of numerous pleas to attend better to the so-called criterion problem (Campbell, 1990 Dunnette, 1963 Wallace, 1965). Appreciation of the need to better understand the performance side of the equation prior to consideration of the predictor side has increased, thanks in part to some influential sources (Austin & Villanova, 1992 Binning & Barrett, 1989 Campbell, 1990). Consistent with this concern regarding the nature of performance and much recent research, we discuss the differences between task and conceptual performance. We also discuss the possibility of a third major performance dimension adaptive performance.

Ishaan S Kalha and Frank A Sinicrope

Surveillance of Barrett's Esophagus Barrett's esophagus is an acquired condition in which specialized metaplastic intestinal epithelium with goblet cells replaces the normal stratified squamous epithelium anywhere in the esophagus. The relationship between long-standing gastroesophageal reflux disease (GERD), the development of specialized intestinal metaplasia in the distal esophagus, and subsequent progression to adenocarcinoma has been clearly established. Once Barrett's esophagus is diagnosed, it is critical to extensively biopsy the segment of Barrett's epithelium to exclude dysplasia and cancer. Management of Barrett's esophagus should focus on relieving symptoms of GERD and performing endoscopic surveillance at appropriate intervals. The timing of surveillance endoscopy is governed by the presence of mucosal dsyplasia and its pathologic grade. Recommendations about endoscopic surveillance intervals will undoubtedly be modified as the natural history of Barrett's esophagus...


This volume honors the following dedicated clinicians and researchers who taught me about the biology and treatment of germ cell tumors A. Munro Neville, MD, PhD Sir Michael Peckham, MD Eadie Heyderman, MD Ann Barrett, MD Timothy McElwain, MD (deceased) B. J. Kennedy, MD Elwin E. Fraley, MD and Paul Lange, MD. It also reflects my continuing affection and respect for my patients, who have battled this disease and who have helped to overcome it for future generations.

Theoretical Analysis

The management of Barrett's esophagus remains a controversial area. Most patients will die from Barrett's rather than from an esophageal adenocarcinoma. However, in a patient with Barrett's esophagus, it is now possible to remove abnormal areas and resurface the entire lower esophagus using a variety of endoscopic techniques. The question remains, who should be treated Many studies have looked at treating metaplasic Barrett's, which can be easily ablated. Currently, ablation is not widely used nor recommended for patients with metaplasia only. Most usually, treatment is restricted to patients who are detected to have high-grade dysplasia, at risk of malignant degeneration, or patients with an early Barrett's adenocarcinoma. Other strategies are being explored for the large numbers of patients with Barrett's metaplasia. Treatment of dysplasia demands an obsession with regression whereas prevention of progression is the correct approach for metaplasia. Most patients in this latter group...


The role of antireflux surgery in Barrett's esophagus is of proven value to patients with significant symptoms and in the prevention of complications of stricture. Antireflux surgery is better than medical therapy at inducing resolution of metaplastic epithelium but this has yet to be proven of clinical value to the patient. Its role in cancer prevention is theoretically attractive, but studies so far have been disappointing in terms of cancer outcome. There is some value in using antireflux surgery as an adjunct to ablation, although even this should be in the context of controlled clinical trials. It is not advisable to recommend antireflux surgery for patients with Barrett's esophagus on the basis of potential protection against cancer development. From a scientific standpoint, it would be of great interest if an early antireflux operation could be performed in the context of a randomized, controlled trial in patients in their 40s and followed for 25 years to the peak age of...

Concluding Summary

Surgical resection with lymphadenctomy is the treatment of choice for all adenocarcinomas of the esphagogastric junction prior to generalization of the disease. Multimodal protocols, with neoadjuvant treatment, are an option when the likelihood of achieving an RO-resection is low. Classification of AEG tumors is best performed as suggested by Siewert and collegues This allows the surgical strategy to be tailored to the oncological problem, the procedures to be standardized, and helps to make results from different institutions comparable. We believe the best approach to AEG I tumors, which are mostly Barrett's cancers, is an abdominothoracic en bloc esophagectomy and reconstruction with gastric pull-up and intrathoracic anaostomosis. A prospectively randomized trial from the Netherlands provides some support for this notion. Extended gastrectomy with lymphadenectomy of the abdominal and lower mediastinal compartment is the preferred approach to AEG II and III tumors. Only in case of...

Epidemiology of GERD

However, the heterogeneity of this classification does not allow to differentiate, as an example, among esophagitis due to GER or due to other less common causes, such as infection or ingestion of drugs and chemicals. It does also not allow grading of esophagitis severity, as achievable for example by the Los Angeles system or the Savary-Miller classification finally, the presence of Barrett's esophagus or extra-esophageal complications of GERD are left out from the ICD-9 classification, which is therefore not particularly helpful. It should not be forgotten, also, that GERD is very seldom a cause of death and rarely causes hospital admission. National incidence and prevalence data are therefore mainly estimated from interviews and are subject to over and under-reporting problems. It has also been claimed that, at least for prevalence studies, the external validity of these data is suspected and hardly generalizable worldwide 7 .

Communicable Disease

A study of suicides from 1970 through 1992 among persons aged 15 to 34 in California found that immigrants were underrepresented among the 32,928 deaths (Sorenson and Shen, 1996b). Firearms were the most common method of suicide among both immigrants and U.S.-born individuals, and the home was the most common site for suicide among both groups. Foreign-born latinos, who came primarily from Mexico, appeared to account for the apparent lower risk of suicide. They appeared to be at higher risk of suicide than their counterparts in Mexico, but at lower risk than their counterparts born in the U.S. (Sorenson and Shen, 1996b). It has been hypothesized that the tendency of immigrants to settle in ethnic enclaves in large cities, close to other immigrants as well as family and friends, may serve as a preventive factor for suicide by reducing social isolation


Biolistics, the other gene transfer technique, does not rely on Agrobacterium. Here, a physical means is used to force foreign DNA into plant cells. Back in 1987, researchers came up with an idea that must have found its origins in the Wild West. They reasoned that DNA, somehow absorbed on the surface of microscopic metal particles, could actually be shot at plant cells by using a gun. In this way, a DNA bullet of sorts would penetrate the plant cell wall, and that DNA would become expressed in the plant cell. And it worked DNA can indeed stick temporarily to microscopic gold or tungsten beads. This shot is loaded into a gun (in early models, the barrel of a .22 caliber was sawed off and the gun welded to a thick metal lid covering a metal firing chamber), and the gun is fired at the plant target. The discharge must be powerful enough for the beads to penetrate the plant cells, but not so powerful as to splatter the sample all over the chamber. You might guess that this was rather...

Ara macao

Conservation status Scarlet macaw populations are declining as habitat is destroyed when trees are cut down. Smuggling also reduces the population. In 2003, poachers armed with guns followed biologists in a Guatemala reserve, an area set aside to protect species. The poachers stole macaw eggs, knowing there is a demand for the birds.

Aspartic Proteases

Meek (1998) Comprehensive Biological Catalysis A Mechanistic Reference 1 , 327. N. D. Rawlings & A. J. Barrett (1995) Meth. Enzymol. 248, 105. E. Lolis & G. A. Petsko (1990) Ann. Rev. Biochem. 59, 597. Selected entries from Methods in Enzymology vol, page(s) Active site, structure, 241, 214 catalytic mechanism, 241, 223224 crystal structure, 241, 214, 216 comparative studies with HIV protease catalytic properties, 241, 205-224 evolutionary relationships, 241, 196-197 screening for HIV-1 protease inhibitors, 241, 318-321 structure, 241, 254-257, 280 substrate specificity, 241, 255, 283 .

Cartridge Cases

Occasionally one will encounter a fired cartridge case having a series of parallel longitudinal markings impressed on the case (Figure 2.6).4 These marks may be either linear areas of swelling or linear deposits of soot. Such markings are a consequence of a fluted chamber. During manufacture, small parallel grooves have been cut into the wall of the chamber permitting powder gases to surround the cartridge case to allow the neck of the cartridge case to float on gas, thus aiding extraction. They are found in rifles, pistols, submachine guns, and machineguns. Flute marks may be present only on the neck or shoulder area of cases or along most of its length. The number of grooves may vary from 2 to 18. Heckler-Koch rifles, submachine guns, and pistols typically have fluted chambers. In the HK-4 pistol, there are 3 flutes that are designed to retard cartridge case extraction rather than facilitate it.

Falling Bullets

In some parts of the country, individuals celebrate New Years' Eve and July 4th by shooting guns in the air. Rarely, deaths are reported due to this practice. In most of these instances, the gun was probably not pointed straight up but at an angle to the horizon. In such a case, it is not unexpected for serious injuries to occur even if the bullet has traveled a great distance as a .30 caliber military rifle round has a maximum effective range of 4000 yards.


Starch is a polymer, or chain, of glucose molecules containing both amylose and amylopectin. Amylose is the straight-chain form of this polymer, while amylo-pectin is the branched form. Starch is the main carbohydrate food reserve in plant seeds and tubers and while it forms an important part of human nutrition, it also provides a useful raw material for industry. Amylopectin has unique physicochemical properties that makes it attractive for a vast range of non-food purposes. Most industrial uses normally involve modification by physical, chemical or enzymatic methods to alter its properties for specific purposes. There is an advantage, however, in producing a wider range of natural starches or derivatives to circumvent the need for processing steps since this is expensive and some constitute an environmental load. Transgenic potatoes and maize producing amylose-free starch have indeed been developed and are ready to enter the market. Even the creation of transgenic plants with more...


Sixty-eight percent of the murders in the United States in 1995 were committed with firearms, 12.7 with knives or other cutting instruments, and 5.9 with personal weapons (hands, fists, feet, etc.). Over 88 of the victims of male murderers were males, but only 9 of the victims of female murderers were females. Over 93 of the victims of black murderers were blacks. Of the murders committed in the United States in 1995,83 occurred during robberies, narcotics law violations, or other felonies 53 were committed during arguments or other nonfelonious acts in the remaining 29 , the circumstances were not known (US. Department of Justice, 1996).

Forcible Rape

The two most frequent crimes in the violent offenses category used by the FBI in determining its annual crime index are robbery and aggravated assault. Whereas the murder rate in 1995 was 8.2 and the forcible rape rate was 37.1 per 100,000 inhabitants, the rates for robbery and aggravated assault were 230.9 and 418.3, respectively. Robbery is defined as taking or attempting to take anything of value from the care, custody, or control of a person or persons by force or threat of force or violence and or by putting the victim in fear (U.S. Department of Justice, 1996, p. 26). Aggravated assault is defined as an unlawful attack by one person upon another for the purpose of inflicting severe or aggravated bodily injury (U.S. Department of Justice, 1996, p. 31). Whereas robberies are more frequent during the fall, the frequency of aggravated assaults is greater during the summer months. Also, unlike assaults, robberies are at least four times as likely to occur on a street or highway as in...


Barrett's esophagus is an endoscopically recognizable change in the esophageal mucosa that has been defined in terms of histopathology Barrett's esophagus is an acquired condition in which specialized meta-plastic intestinal columnar epithelium with goblet cells replaces the normal stratified squamous epithelium anywhere in the esophagus (Gadour and Ayoola, 2002). A clinical definition of Barrett's esophagus has been difficult to achieve. The controversy surrounding the clinical definition of Barrett's esophagus stems from the difficulty in identifying the true squamocolumnar junction (z-line) and the gastroesophageal junction, as these 2 locations do not always coincide. Identifying columnar-lined esophagus at endoscopy requires precise criteria by which to delimit the esophagus and the stomach. If the squamocolumnar junction becomes located proximal to the gastroesophageal junction, then the intervening mucosa between the 2 junctions will be lined by a segment of columnar...


Barrett's esophagus is found in 3.5 to 7 of persons with GERD (Cameron and Carpenter, 1997). Although Barrett's esophagus develops in only a minority of patients with GERD, diagnosis of Barrett's esophagus has increased significantly over the past 30 years. Whether the increased recognition of Barrett's esophagus is a real phenomenon or simply parallels the increased use of endoscopy is somewhat controversial (Conio et al, 2001). The prevalence of Barrett's esophagus increases with age and reaches a plateau by the seventh decade. Barrett's esophagus has been shown to develop more than 20 years before the mean age of diagnosis or the subsequent development of esophageal adenocarci-noma (Cameron and Lomboy, 1992). The actual prevalence of Barrett's esophagus may never be known because many patients with the condition are asymptomatic and consequently do not seek medical attention. However, an autopsy study estimated the prevalence of Barrett's esophagus at 376 per 100,000 persons...


Barrett's esophagus appears to develop as a consequence of a complex interaction between molecular, genetic, and environmental factors (Figure 20-1). As mentioned in the preceding section, GERD has been established as a strong risk factor for esophageal adenocarcinoma (Spechler, 2001). Under normal circumstances, the reflux of gastric contents into the esophagus is prevented by a functioning lower esophageal sphincter. Dysfunction of the lower esophageal sphincter, in many cases in combination with the presence of a hiatal hernia, leads to failure of an effective barrier. In such cases, esophageal mucosal damage results from the chronic exposure to gastroduodenal contents (Buttar et al, 2001b). One hypothesis suggests that Barrett's esophagus develops as a result of an extension of gastric columnar epithelium into the esophagus, a process called creeping substitution. If this were the case, then older patients would be expected to have longer segments of Barrett's esophagus than...

Dysplasia and Cancer

Dysplasia can occur in metaplastic Barrett's epithelium and is a neoplas-tic change. At present, dysplasia is the best indicator of cancer risk in patients with Barrett's esophagus. The grading of dysplasia in Barrett's esophagus is based on the system used for ulcerative colitis (Riddell et al, 1983). Interobserver variability in the recognition, grading, and repro-ducibility of detection of dysplasia in Barrett's esophagus is problematic (Reid et al, 1988 Montgomery et al, 2001). The finding of dysplasia of any grade warrants repeat endoscopy with intensive biopsy of the area of dys-plasia to exclude coexisting carcinoma (Sampliner, 2002). The finding of high-grade dysplasia necessitates repeat endoscopy with particular attention to any mucosal lesion. An intensive biopsy protocol using therapeutic endoscopy and jumbo forceps is recommended. An expert pathologist should confirm the presence of high-grade dysplasia. The extent of high-grade dysplasia is also important. High-grade...


Adenocarcinoma develops in Barrett's esophagus by a multistep process in which specialized metaplasia progresses to dysplasia, then to early adenocarcinoma, and eventually to invasive disease (Figure 20-1). A variety of epithelial biomarker studies have been performed in Barrett's esophagus to identify key cellular and molecular markers that may provide valuable data on the risk of disease progression and cancer development. Markers of cancer risk, including changes in DNA content, have been identified, but these abnormalities have yet to be validated in multicenter studies with routine follow-up. Therefore, none of these potential bio-markers have yet been incorporated into routine patient care. Once and if such markers are validated, their use in clinical practice will have the potential to permit stratification of patients by risk and to enable a more individualized and perhaps more selective approach to endoscopic surveillance. Furthermore, an increased understanding of the...

Final Conclusions

Levine, 1997 McFarland, Ross, & DeCourville, 1989), sex-related stereotypes about emotional experience (Eisenberg & Lennon, 1983 LaFrance & Banaji, 1992), personality (Feldman Barrett, 1997), and intensity of emotional experience (Kahneman, 1999 Robinson & Clore, 2002b). Recent work suggests that this discrepancy is due to two different emotional reporting mechanisms recall up to about 2 weeks is based on actual experience, and longer-term recall is based on semantic beliefs about typical experiences (Robinson & Clore, 2002a, 2002b). Thus, whereas current and short-term reports of affective experience are based on actual recall of affect episodes, retrospective reports about frequency of emotions can be biased by a number of factors associated with semantic belief structures. Such evidence for other important organizational variables is lacking.

The Autopsy Report

In preparing an autopsy report in a death caused by gunshot wounds, it is always best to group the description of wounds in one area labeled Evidence of Injury, rather than scattering this information throughout the protocol. Thus, when a bullet entering the left chest perforates the left lung, the heart, the right lung, and exits the back, one should have all this information in one area of the autopsy report rather than scattering it among the External Examination and the description of the individual internal organs. Once the description of the injury to the organ has been made in this section, there is no need to redescribe the injury in the area of the report devoted to the organs. Measurements as to location may be in either the English or the metric system. Since most lay people in the U.S. do not understand the metric system, and the majority of people who will see a forensic autopsy report are lay people, the English system is preferable. Describing a gunshot wound in...

Needle Core Biopsies

Biopsy needles range in calibre from 22 gauge (skinny core needle) through 18 gauge to the standard 14 gauge Tru-Cut needle. The introduction of automated, spring-loaded 18 gauge core biopsy guns has been accompanied by a dramatic increase in the use of core needle biopsy of the breast, prostate and bone or soft tissue masses. Such biopsies are increasingly performed by a radiologist or specialist clinician using ultrasound guidance. Stereotactic core biopsy is frequently used by radiologists in the investigation of breast lesions such as microcalcification detected by screening mammography.


The pathological implications of surveillance, treatment and surgery for Barrett's oesophagus. Curr Diagn Pathol 2003 9 242-251. Biddlestone LR, Bailey TA, Whittles CE, Shepherd NA. The clinical and molecular pathology of Barrett's oesophagus. In Kirkham N, Lemoine NR (eds). Progress in pathology 5. Medical Media Limited. London 2001 57-80. British Society of Gastroenterology. Guidelines for the diagnosis and management of Barrett's columnar-lined oesophagus. http clinical-prac guidelines.htm Coad RA, Shepherd NA. Barrett's oesophagus definition, diagnosis and patho-genesis. Curr Diagn Pathol 2003 9 218-227. Galmiche JP, Pallone F (eds). Barrett's oesophagus and oesophageal adeno-carcinoma. Gut 2005 54(Suppl. 1) i1-i42. Paraf F, Fl jou J-F, Pignon J-P, F k t F, Potet F. Surgical pathology of ade-nocarcinoma arising in Barrett's esophagus. Am J Surg Pathol 1995 19 183-191. Chandrasoma P. Controversies of the cardiac mucosa and Barrett's oesophagus. Histopathology...


Barium Meal

Cross-section and CT scan at approximately vertebral level T12, where the portal triad is located. (A) Schematic diagram showing where the cross-section was taken. (B) Cross-section through a cadaver. (C) CT scan. Note the various structures indicated by the key. In addition, note the psoas major and quadratus lumborum muscles along the sides of the vertebral body. The right and left lobes of the liver are shown in relation to the portal vein, common hepatic artery, and inferior vena cava. The right adrenal gland lies posterolateral to the inferior vena cava. The left adrenal gland lies between the body of the stomach and the abdominal aorta. (Reprinted with permission from Barrett CP, Anderson LD, Holder LE, et al Primer of Sectional Anatomy With MR and CT Correlation, 2nd ed. Baltimore, Williams & Wilkins, 1994, pp 75, 76.) Figure 9-5. Cross-section and CT scan at the level of the gallbladder. (A) Schematic diagram showing where the cross-section was taken. (B)...

Antireflux barrier

Hiatal hernia is a fairly common finding in adults, with estimates of its prevalence ranging from 10-80 . Although widely believed to be a predisposition for reflux, it may be also be an incidental finding in asymptomatic persons 22 . Hiatal hernias have affected family members across multiple generations, leading some to suggest an autosomal dominant pattern of inheritance 23 . The diaphragmatic crura normally reinforce the LES as an anti-reflux barrier, and relax when a TLESR occurs. The lack of this reinforcement assumes significance when abrupt changes in abdominal pressure, such as during straining, overcome the LES pressure in a person with a hiatal hernia. Hiatal hernias are more prevalent in severe reflux disease, and have also been reported to be common in conditions associated with severe reflux, such as cystic fibrosis and neurological impairments 24 . Of 718 children with reflux, 6 were identified to have a hiatal hernia, and nearly a fourth of them were neurologically...

Erosive esophagitis

The presence of erosive esophagitis has a good correlation with results of 24 h pH monitoring showing increased esophageal acid exposure. In a study by DeMeester etal 13 , the combination of typical reflux symptoms (i.e., grade-II or -III heartburn and or regurgitation, scale of severity 0-3) and the presence of erosive esophagitis or Barrett's esophagus on en-doscopy had a 64 sensitivity and 97 specificity for accurately diagnosing GERD as defined by a positive 24-hr ambulatory pH result. A study of 24 controls and 64 patients with reflux symptoms (all of whom underwent 24-hr pH monitoring), showed that the distinction in degree of esophageal acid exposure was excellent between asymptomatic controls and patients with severe erosive esophagitis (sensitivity and specificity both 100 by logistic regression) but discrimination was relatively poor when asymptomatic controls were compared to symptomatic patients without esophagitis (71 and 79 by logistic regression) 14 .

Shotgun Wounds

Shotgun Contact Wound

Contact shotgun wounds of the head are among the most mutilating firearms wounds there are. Extensive destruction of bone and soft tissue structures with bursting ruptures of the head are the rule rather than the exception. These are the wounds of which an individual is said to have blown his head off. In some cases, this is almost literally true. The skull may be largely fragmented and the brain pulpified. Large fragments of the cranial vault and cerebral hemispheres are often ejected from the head. The scalp is extensively lacerated. With similar sites of entrance, the internal injuries produced by shotguns of different gauge are very similar. This is not the case for external injuries. Harruff noted a marked difference in the external injuries depending on the gauge of the weapon used.6 In the case of intraoral wounds, in 74 of the cases in which a 12 gauge shotgun was used there were bursting injuries extending from the mouth to the scalp. For 20-gauge shotguns, only 9 of the...


Dihydroxyacetone (C3H6O3) is a white, crystalline, hygroscopic powder. This 3-carbon sugar forms a dimer in freshly prepared aqueous solution (Fig. 1). With heating to effect a solution in alcohol, ether, or acetone, it reverts to the monomer. The monomeric form is more important in the browning reaction, which leads to the skincolor change 4 . DHA The Maillard or browning reaction has been defined as the reaction of an amino group of amino acids, peptides, or proteins with the glycosidic hydroxyl group of sugars. DHA in the context of this reaction may be considered a 3-carbon sugar, reacting with free amino groups available as amino acids, peptides, and proteins supplied by the keratin to form products or chromophores referred to as melanoidins 5 . Melanoidins have some physicochemical properties similar to naturally occurring melanin 6 .

Red fox

Squirrel Monkey Location

The fox is the sly trickster in the folklore of the Old World. The term sour grapes comes from Aesop's anthropomorphic fox. Predation of chickens has probably been going on for several thousand years, but the nineteenth century brought more conflict as game birds and lambs born in the fields provided food. Foxes have been persecuted by guns, hounds, and poison, but have seldom been exterminated. The sport of fox-hunting in England has ensured the survival of the quarry, and now that the sport is close to banned, the fox's range may contract. A vigorous campaign to control foxes in western Europe so as to limit the spread of rabies, has not eliminated the species.

Complicated GERD

The important esophageal complications of chronic reflux are strictures, Barrett's esophagus, and adenocarcinoma. Aggressive medical management, preferably with proton pump inhibitors, and close follow-up, using tests to assess symptoms and severity of reflux, are warranted in complicated GERD. Surgical management is contemplated in patients who remain unresponsive to medical therapy. Exposure of the esophagus to acid and perhaps to pepsin is crucial to the pathogenesis of reflux strictures hiatal hernia and esophageal dysmotility are other risk factors 80 . Reflux strictures are typically located in the distal third of the esophagus, and should be distinguished from congenital esophageal stenosis and other types of strictures caustic (generally more proximal), eosinophilic, postoperative anastomotic, following radiation therapy or sclero-therapy, or (rarely in children) malignant. Esoph-ageal mucosal biopsies obtained below the stricture help to confirm the diagnosis of reflux...

Biopsy Specimens

Two main types of oesophageal endoscopy exist, namely rigid and flexible. Rigid oesophagoscopy is only occasionally used to provide larger biopsies when previous flexible endoscopy samples have proven non-diagnostic. Specific lesions such as polyps or ulcers necessitate multiple targeted biopsies which may be supplemented by brush cytology of the mucosal surface. Mapping and annual biennial surveillance of flat mucosa for Barrett's metaplasia and dysplasia is achieved by multiple segmental (every 2 cm) and quadrantic biopsies. The basis of an oesophageal stricture may be easier to demonstrate if malignant in nature because of carcinoma ulcerating the squamous epithelium, whereas a benign peptic stricture due to submucosal or mural fibrosis is often not accessible to mucosal biopsy. Endoscopic biopsy of achalasia or oesophageal webs is often unrewarding as it provides intact surface mucosa only.

Cystatin B

Cystatin B is a member of the cysteine proteinase inhibitor superfamily (PROSITE PDOC00259 reviewed in Turk and Bode 1991 Turk et al. 1997, 2002b). This name was first used to describe an inhibitor of papain and related endopeptidases isolated from chicken egg white (Barrett 1981). Residues 46-50 of cystatin B constitute the so-called QVVAG domain, which is highly conserved in type 1 and plant cystatins. This region is deleted in some EPM1 patients with splice site mutations as discussed later. In type 2 cystatins only Q46 and G50 are consistently present. Kininogens contain three QVVAG domains and are predicted to have arisen from type 1 cystatins by gene triplication (Muller-Esterl et al. 1985 Rawlings and Barrett 1990).


During the Vietnam war, the United Statesmilitaryusedammunitionloaded with steel flechettes. A flechette is a small arrow-shaped projectile with a metal tail fin. It is made in both 8- and13-gr. form. The8-gr. flechette, which is the more common type, measures 1 mm in diameter by approximately 2.7 cm in length. Flechettes were fired from 90-mm recoilless rifles, 90-mm guns, 12-Gauge shotgun shells loaded with flechettes were manufactured for military use. These rounds have hulls of either Federal or Western manufacture. The Federal round contains 25 flechettes the Western round 20. The tips of the flechettes are exposed in the Federal rounds but are concealed in the Western by a crimped mouth. The Winchester shells are packed in military cardboard boxes of 10 shells each. The boxes are labeled 18.5-mm Flechette Plastic Case and state that the shells should be fired in cylinder bore guns only. The 20 flechettes in each round weigh 7.3 gr. each and are packed in a plastic cup with...


Many approaches may be taken to the evaluation of the individual presenting, for the first time, with symptoms indicative or suggestive of GERD. Decisions regarding the extent of assessment are based on individual patient factors and on some generic issues. With regard to the former, patient age and nature of symptomatology are fundamental few would dispute the appropriateness of endoscopy in a 63-year old patient with heartburn and dysphagia referred to the lower esophagus. More controversial are the generic issues and one, in particular, Barrett's esophagus. One's assessment of the role of Barrett's in the pathogenesis of esophageal adenocarcinoma and one's attitude to the efficacy and appropriateness of screening and surveillance policies for this manifestation of GERD will determine enthusiasm for such approaches to GERD as once in a life-time endoscopy for every GERD patient or endoscopy for all over 50. In the absence of conclusive data, approaches are largely empiric and extend...