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Another explanation is that the index patient acquired the infection during hospitalization. The family cluster cases describe a disease spectrum that includes an atypical presentation by the index patient, severe disease and death in one previously healthy young contact, and milder illness in two other young family members who were close contacts. Relatives and health staff contacts have remained healthy for the past 6 months.
Three of the four patients in this cluster had gastrointestinal symptoms, and two had diarrhea. Hemodialysis was required only for the index patient, who had preexisting chronic illness; one other patient had an elevated creatinine level on admission. Lymphocytopenia, another prominent feature of SARS-CoV infection, was found in all four patients and in the two patients whose cases have been published previously.
Chest radiography of all patients showed lung infiltrates soon after symptom onset; three of the four patients with progression to pneumonia had airspace disease, in contrast with patients with SARS-CoV pulmonary infection, who more often had atypical pneumonias that were characterized by interstitial infiltrates. This report suggests that transmission of MERS-CoV occurred among family members but indicates that the risk of MERS-CoV infection among close contacts of patients is low, although infection risk is increased in patients with immunosuppression or coexisting illnesses.
Current global concern rests on the ability of MERS-CoV to cause major illness among the close contacts of patients, particularly in family members, work colleagues, and health care workers. Serologic studies are required to further define the epidemiologic features, infectivity among asymptomatic contacts, and prevalence in the community of MERS-CoV.
The finding of gastrointestinal symptoms in three of the four patients in this study may be an important finding for MERS-CoV epidemiology, hospital infection-control measures, and contact isolation. Serologic testing of close contacts of patients with this disease will help to define local transmission rates and risk factors.
The latest WHO interim surveillance guidelines revised on March 18, have removed this geographic restriction 10 and will enable screening over a wider geographic area, which will allow for a more accurate definition of the epidemiologic features of MERS-CoV infection. Several major research challenges remain: To achieve these goals, more coordinated international collaboration and sharing of clinical and research data and other information are urgently required.
Although current data indicate that MERS-CoV does not appear to be as readily transmissible among humans, as was observed with the SARS-CoV epidemic incontinued risk assessment, surveillance, and vigilance by all countries are required.
Disclosure forms provided by the authors are available with the full text of this article at NEJM. Address reprint requests to Dr. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.
N Engl J Med ; Genetic sequence information for scientists about the novel coronavirus Health Protection Agency, http: August 15, http: Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction.
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Ciottone's Disaster Medicine, Gytis Dudas, Andrew Rambaut. Journal of Korean Medical Science Abdullah Assiri, Glen R. Bin Saeed, Mutwakil A. Further complicating diagnostic issues, Hayward had contended that even the normal esophagus could be lined by up to 2 cm of cardia-type epithelium. These factors created major problems for investigators, because accurate diagnostic criteria are a prerequisite for a meaningful study of a disease.
For example, Skinner et al. By adhering to such diagnostic guidelines, physicians minimized the problem of mis-diagnosis, but failed to identify short segments of metaplastic epithelium in the distal esophagus.
That practice was challenged inwhen Spechler et al.
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Numerous subsequent studies confirmed that short segments of intestinal metaplasia frequently line the distal esophagus of individuals with no signs or symptoms of GERD. In esophageal squamous cell lines, for example, acid and bile induce the expression of caudal homeobox genes such as CDX1 and CDX2. In adult cells, alterations in homeobox genes might alter cellular phenotypic features. Tumor initiation is the process in which cells are changed so that they are able to form tumors. Studies have shown that esophageal cells exposed to acid develop DNA double-strand breaks that might contribute to tumor initiation.
In patients with GERD, the distal esophagus can be exposed to high concentrations of nitric oxide and other nitrosating species, which are generated from the nitrate in green, leafy vegetables in the diet.
Iron also might have a role in the development of esophageal cancer.
After the surgical induction of reflux in rats, the rate of development of esophageal adenocarcinoma is substantially higher in animals that receive iron supplementation. In general, both alleles of a tumor suppressor gene must be silenced to contribute to carcinogenesis. The first silencing event allele 1 usually involves a DNA nucleotide sequence change mutation e.
The second silencing event allele 2 can also be a sequence change mutation, but more commonly involves loss of a chromosome segment after a faulty cell division so-called loss of heterozygosity or LOH. Methylation of DNA cytosine residues in the gene promoter region is another common gene silencing mechanism. LOH at TP53 is associated with a fold increase in the rate of progression to cancer. A large, nested, case-control study found that TP53 staining was increased in biopsies from patients who developed esophageal adenocarcinoma compared with controls, with an odds ratio of Cells that lose TP53 expression often acquire an abnormal content of DNA tetraploidy or aneuploidy that can be detected by flow cytometry.
These DNA changes correlate with increased proliferation and expansion of the proliferative compartment towards the mucosal surface. Widespread LOH at TP53 and cytogenetic abnormalities are associated with increased cancer risk, perhaps because these changes increase sensitivity to mutagens. Aneuploidy has diverse effects on cell metabolism, proliferation, and immortalization. Aneuploidy at chromosomes 4 and 7 usually occurs early in carcinogenesis, followed by aneuploidy at chromosomes 8 and 17 and then by the loss of the Y chromosome in cells from male patients.
Unfortunately, our understanding of the functional implications of these abnormalities and how they might be used to improve patient care lags behind. Application of concepts from other disciplines, such as evolutionary biology and bioinformatics, should facilitate progress in understanding causality.
The ablative therapies can be further classified as heat-generating thermal techniques radiofrequency ablation, multipolar electrocoagulation, and argon plasma coagulationphotochemical techniques photodynamic therapyand cryotherapy. Table 1 summarizes the evidence for efficacy, advantages, and limitations of each technique. Endoscopic mucosal resection EMR involves the removal of mucosal and submucosal tissue, usually after the targeted mucosal segment is elevated by the submucosal injection of fluid. The banded segments are then removed with a snare. The band ligation method allows multiple resections to be completed in a single intubation and does not always require submucosal fluid injection before banding.
The 2 EMR techniques have been compared; the suck and cut method provides larger tissue samples whereas the band ligation technique is faster and less expensive for multiple resections. Compared to conventional endoscopic biopsy methods, EMR allows for more precise characterization of neoplasia, less inter-observer variation among pathologists, and more accurate assessments of dysplasia grades and the depths of invasion.
Family Cluster of Middle East Respiratory Syndrome Coronavirus Infections
Results of the 2 approaches are summarized in table 1. Accurate T staging of the depth of neoplastic involvement is required to determine whether endoscopic therapy can be considered definitive. Endoscopic submucosal dissection ESD has been used primarily in Japan, predominantly for the treatment of gastric neoplasia. ESD starts with injection of fluid into the submucosa, followed by incision around the mucosal segment to be removed using a cutting device e. The major proposed advantage of ESD over EMR is the ability to remove a neoplastic lesion en-blocwhich provides more precise determination of its vertical and lateral margins and, perhaps, greater potential for the complete removal of all neoplastic cells.
However, ESD is a technically challenging and lengthy procedure that sometimes requires hours to complete, and serious complications such as perforation are frequent. Multipolar electrocoagulation MPEC involves the application of thermal energy to the mucosa using an electrode-tipped, 7F or 10F catheter that is advanced through the working channel of the endoscope. Because MPEC is a bipolar device, however, it might be used to eradicate residual areas of intestinal metaplasia for patients who have implanted cardiac devices. Unlike MPEC, argon plasma coagulation APC is a non-contact technique in which monopolar energy is delivered to tissue using ionized argon gas.
This might reflect the relatively superficial injury inflicted by APC. This interaction leads to the generation of toxic, singlet oxygen molecules that damage tissue. The photosensitizers used for PDT include porfimer sodium, which is administered intravenously, and 5-aminolevulinic acid ALAwhich can be administered orally. Escobedo MoralesM. Journal of Molecular Graphics and Modelling 74 RodriguesRui M. DominguesRui L.
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Abdel-RahmanSameh S. Hanjour began making cross-country flights in August to test security, and tried to rent a plane from Freeway Airport in Maryland; though he was declined after exhibiting difficulty controlling and landing a single-engine Cessna There, Hanjour claimed that his first name translated as warrior when a gym employee asked if there was an English translation of their Arabic names. Hani actually translates as "contented. No evidence was ever uncovered that they had met, or knew of each other's presence. The flight was scheduled to depart at 8: Using the flight intercom, Hanjour announced the flight was hijacked.
At the end of the turn, it was descending through 2, feet mpointed toward the Pentagon and downtown Washington. After the September 11 attacks, Hanjour's family in Saudi Arabia vehemently stated that they could not, and would not, believe he had been involved as one of the hijacker pilots, and also stated that he had phoned them just eight hours prior to the hijackings and his voice did not sound strange or unusual at all.
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American Airlines Flight Retrieved September 1, Sun; George Lardner Jr. Joint Intelligence Committee Inquiry. Retrieved September 2, In His Quest to Be a Pilot". The New York Times. Archived from the original PDF on October 12, Retrieved October 6, Archived from the original on February 2, Retrieved July 30, Archived from the original on January 6, Retrieved May 4, The San Francisco Chronicle. Archived from the original on August 30, Retrieved October 1, Archived from the original on April 5, Retrieved March 27, The Washington Post, Page A