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1.
Miniature swine provide a preclinical model of hematopoietic cell transplantation (HCT) for studies of graft-versus-host disease. HCT between MHC-matched or ‑mismatched pigs can be performed to mimic clinical scenarios with outcomes that closely resemble those observed in human HCT recipients. With myeloablative conditioning, HCT across MHC barriers is typically fatal, with pigs developing severe (grade III or IV) GVHD involving the gastrointestinal tract, liver, and skin. Unlike rodent models, miniature swine provide an opportunity to perform extended longitudinal studies on individual animals, because multiple tissue biopsies can be harvested without the need for euthanasia. In addition, we have developed a swine GVHD scoring system that parallels that used in the human clinical setting. Given the similarities of GVHD in pigs and humans, we hope that the use of this scoring system facilitates clinical and scientific discourse between the laboratory and the clinic. We anticipate that results of swine studies will support the development of new strategies to improve the identification and treatment of GVHD in clinical HCT scenarios.Abbreviations: BMT, bone marrow transplantation; GVHD, graft-versus-host disease; GVL, graft-versus-leukemia; HCT, hematopoietic cell transplantation; TBI, total-body irradiation  相似文献   

2.

Background

Chronic abdominal pain (CAP) is a common indication for gastroenterology referrals. More insidious causes of CAP isolated to the small bowel, such as malignancies and Crohn’s disease, are rising in incidence and causing more gastroenterologists to evaluate their patients with video capsule endoscopy (VCE). However, the role of VCE in patients with CAP is still unclear.

Aims

We assessed the efficacy of VCE in patients with CAP and whether it led to findings that contributed to disease management and meaningful interventions.

Methods

This retrospective study evaluated 607 capsule endoscopy studies at an open referral endoscopy unit. Ninety of the studies were for CAP. These studies were compared to those performed for other indications to compare diagnostic yield. In addition, we investigated whether VCE led to an intervention that improved clinical outcomes.

Results

Overall, the number of abnormal findings in CAP patients was significantly lower than VCE performed for other indications (24.4% vs 39.0%, respectively p = 0.009). When patients with CAP presented with other pertinent clinical findings (e.g. nausea, weight loss, anemia, history of in inflammatory bowel disease, etc.), the likelihood of an abnormal finding increased to a level that was not different from those who received VCE for other indications (27.1%, p = 0.10). The findings from VCE lead to changed management and improved outcomes in 16.2% of CAP patients with associated symptoms. However, the subgroup that benefited the most were those who had a prior history of Crohn’s disease. Patients with CAP who did not have any associated symptoms continued to have a significantly lower abnormal finding rate compared to those who received VCE for other indications (19.4%, p = 0.03) and VCE rarely led to a change in management that would improve outcomes (5.6%).

Conclusions

VCE for CAP has a lower rate of abnormal findings than other indications. However, VCE is a useful diagnostic tool that can help provide a possible etiology of CAP in patients with associated symptoms. However, a change in management from VCE is likely to be limited to those with a history of Crohn’s disease.  相似文献   

3.
4.
B-mode ultrasonographic examination of the accessory sex glands of boars   总被引:1,自引:0,他引:1  
Clark SG  Althouse GC 《Theriogenology》2002,57(8):2003-2013
Thorough examinations of the reproductive system of boars are generally not performed on normal boars to be used for breeding; only boars with problems undergo a form of a breeding soundness examination. In order for veterinarians to identify pathological conditions, the normal architecture of the accessory sex glands needs to be described. The purpose of this study was to use B-mode ultrasonography to describe the accessory sex glands in the boar and to see if transrectal ultrasonography would be a viable option in which to obtain this data. Initially, cross-sectional saline bath examinations of accessory sex glands were performed on crossbred boar reproductive tracts (n = 4) using B-mode ultrasonography equipped with a 5 MHz dual frequency linear array transducer. In situ examinations were also performed on terminal line crossbred boars (n = 16) ranging in age from 10 to 23 months old using the same ultrasound methodology; four boars were under general anesthesia and the remaining 12 were standing in crates. Eight boars were abstinent for 2 days and the other eight had ejaculates collected 2 h prior to examination. The paired bulbourethral glands are best described as a long oval gland with a uniformly echogenic appearance with a large anechoic space in the center of the gland extending most of its length. The walls of the vesicular glands were found to be thin, with the parenchyma having multiple small echolucent areas that appeared to merge and form a central canal. The prostate gland was best identified as a pecan-sized gland with a uniform echogenic appearance. Visualization of the prostate gland was accomplished with more proficiency using the saline bath ultrasonography as compared to in situ examinations. All of the accessory sex glands could be examined using both methodologies of ultrasonographic examination with a 5 MHz frequency linear array transducer. It was determined that each accessory sex gland could be recognized, and differences between ejaculated and nonejaculated boars could be identified. The results of this study demonstrate that transrectal ultrasonography can be used as a diagnostic aid in assessing the accessory sex glands of boars.  相似文献   

5.
The current accepted standard for evaluating the efficacy of gastrointestinal anthelmintic drugs is necropsy of infected animals followed by a comparison of worm counts between treated and non-treated groups. In this study capsule endoscopy, a minimally invasive method of imaging the small intestine of humans, is evaluated as a possible alternative to necropsy for the purposes of worm quantification in dogs. Eighteen Beagle dogs were included in this study. These dogs were part of a separate trial intended to determine the efficacy of various candidate parasiticides against Ancylostoma caninum via the necropsy standard. Dogs were inoculated with A. caninum L3s 4 weeks prior to treatment with one of the candidate compounds; a control group (n=8) received no treatment. Capsule endoscopy was performed 6-14 days post-treatment, followed by necropsy the following day. Seventeen dogs had complete examinations, i.e. the capsule traversed the small intestine and reached the colon within the battery life of the capsule. A strong correlation (r(s)=0.87, P<0.0001) was observed between the worm counts acquired by capsule endoscopy and necropsy. There was no clear relationship between the ability of the capsule endoscope to detect hookworms and either visibility of the intestinal lumen or small intestinal transit time. Generation of a virtual spatial record of hookworm location from the capsule endoscopy data revealed a temporal trend, with the majority of worms present in the proximal small intestine in the morning versus the central to distal small intestine in the afternoon. Worm distribution as determined by capsule endoscopy closely resembled post-mortem findings. In conclusion, capsule endoscopy shows promise as an alternative to necropsy for the enumeration of A. caninum in the canine small intestine, although further work is required to improve completion rates and optimise intestinal examination.  相似文献   

6.
Docking programs can generate subsets of a compound collection with an increased percentage of actives against a target (enrichment) by predicting their binding mode (pose) and affinity (score), and retrieving those with the highest scores. Using the QXP and GOLD programs, we compared the ability of six single scoring functions (PLP, Ligscore, Ludi, Jain, ChemScore, PMF) and four composite scoring models (Mean Rank: MR, Rank-by-Vote: Vt, Bayesian Statistics: BS and PLS Discriminant Analysis: DA) to separate compounds that are active against CDK2 from inactives. We determined the enrichment for the entire set of actives (IC50 < 10 microM) and for three activity subsets. In all cases, the enrichment for each subset was lower than for the entire set of actives. QXP outperformed GOLD at pose prediction, but yielded only moderately better enrichments. Five to six scoring functions yielded good enrichments with GOLD poses, while typically only two worked well with QXP poses. For each program, two scoring functions generally performed better than the others (Ligscore2 and Ludi for GOLD; QXP and Jain for QXP). Composite scoring functions yielded better results than single scoring functions. The consensus approaches MR and Vt worked best when separating micromolar inhibitors from inactives. The statistical approaches BS and DA, which require training data, performed best when distinguishing between low and high nanomolar inhibitors. The key observation that all hit rate profiles for all four activity intervals for all scoring schemes for both programs are significantly better than random, is evidence that docking can be successfully applied to enrich compound collections.  相似文献   

7.

Background

The 2011 idiopathic pulmonary fibrosis (IPF) guidelines are based on the diagnosis of IPF using only high-resolution computed tomography (HRCT). However, few studies have thus far reviewed the usefulness of the HRCT scoring system based on the grading scale provided in the guidelines. We retrospectively studied 98 patients with respect to assess the prognostic value of changes in HRCT findings using a new HRCT scoring system based on the grading scale published in the guidelines.

Methods

Consecutive patients with IPF who were diagnosed using HRCT alone between January 2008 and January 2012 were evaluated. HRCT examinations and pulmonary function tests were performed at six-month intervals for the first year after diagnosis. The HRCT findings were evaluated using the new HRCT scoring system (HRCT fibrosis score) over time. The findings and survival rates were analyzed using a Kaplan-Meier analysis.

Results

The HRCT fibrosis scores at six and 12 months after diagnosis were significantly increased compared to those observed at the initial diagnosis (p < 0.001). The patients with an elevated HRCT fibrosis score at six months based on a receiver operating characteristic (ROC) curves analysis had a poor prognosis (log-rank, hazard ratio [HR] 2.435, 95% CI 1.196-4.962; p = 0.0142). Furthermore, among the patients without marked changes in %FVC, those with an elevated score above the cut-off value had a poor prognosis (HR 2.192, 95% CI 1.003-4.791; p = 0.0491).

Conclusions

Our data demonstrate that the HRCT scoring system based on the grading scale is useful for predicting the clinical outcomes of IPF and identifying patients with an adverse prognosis when used in combination with spirometry.  相似文献   

8.
An optical fiber biosensor to detect calpastatin has been investigated as a preliminary step in developing tenderness detection instrumentation. Longissimus dorsi samples were taken from beef carcasses (n=21) at 0, 24, 36 and 48h postmortem. Muscle homogenates were assayed for calpastatin activity using traditional methods and an optical fiber biosensor. Warner-Bratzler shear force was also performed on a steak from each carcass at 14d postmortem. Results demonstrated that the measurements with highest correlation between traditional calpastatin assays and optical biosensor readings were taken at 48h postmortem (r=0.597, P< or =0.01), suggesting that this is the best time for use of this biosensor in an on-line grading system. This research further advances the development of a calpastatin biosensor and would be useful in laboratory determination of the presence of biologically active calpastatin concentrations.  相似文献   

9.
A central challenge in interpreting personal genomes is determining which mutations most likely influence disease. Although progress has been made in scoring the functional impact of individual mutations, the characteristics of the genes in which those mutations are found remain largely unexplored. For example, genes known to carry few common functional variants in healthy individuals may be judged more likely to cause certain kinds of disease than genes known to carry many such variants. Until now, however, it has not been possible to develop a quantitative assessment of how well genes tolerate functional genetic variation on a genome-wide scale. Here we describe an effort that uses sequence data from 6503 whole exome sequences made available by the NHLBI Exome Sequencing Project (ESP). Specifically, we develop an intolerance scoring system that assesses whether genes have relatively more or less functional genetic variation than expected based on the apparently neutral variation found in the gene. To illustrate the utility of this intolerance score, we show that genes responsible for Mendelian diseases are significantly more intolerant to functional genetic variation than genes that do not cause any known disease, but with striking variation in intolerance among genes causing different classes of genetic disease. We conclude by showing that use of an intolerance ranking system can aid in interpreting personal genomes and identifying pathogenic mutations.  相似文献   

10.
Summary Standard EEG risk evaluation works on scoring systems that use different types of questionnaires. Here, an alternative for SIDS (Sudden Infant Death Syndrome) risk detection is presented that is based exclusively on EEG data which possibly could substitute the procedure of questioning the parents and allow a direct qualification of the physiological disposition of the individual neonate: Using EEG-characters an approved SIDS-case could be discriminated as well against the group of “healthy” infants as against the “high-risk-group”. The results of this study may confirm the evidence that the EEG analysis can be a promising approach to predict an increased SIDS risk.  相似文献   

11.
《PloS one》2015,10(3)
Although metabolic syndrome is associated with increased risk of cardiovascular disease and events, its added prognostic value beyond its components remains unknown. This study compared the prevalence, severity of coronary artery disease (CAD), and prognosis of patients with metabolic syndrome to those with individual metabolic syndrome components. The study cohort consisted of 27125 consecutive individuals who underwent ≥64-detector row coronary CT angiography (CCTA) at 12 centers from 2003 to 2009. Metabolic syndrome was defined as per NCEP/ATP III criteria. Metabolic syndrome patients (n=690) were matched 1:1:1 to those with 1 component (n=690) and 2 components (n=690) of metabolic syndrome for age, sex, smoking status, and family history of premature CAD using propensity scoring. Major adverse cardiac events (MACE) were defined by a composite of myocardial infarction (MI), acute coronary syndrome, mortality and late target vessel revascularization. Patients with 1 component of metabolic syndrome manifested lower rates of obstructive 1-, 2-, and 3-vessel/left main disease compared to metabolic syndrome patients (9.4% vs 13.8%, 2.6% vs 4.5%, and 1.0% vs 2.3%, respectively; p<0.05), while those with 2 components did not (10.5% vs 13.8%, 2.8% vs 4.5% and 1.3% vs 2.3%, respectively; p>0.05). At 2.5 years, metabolic syndrome patients experienced a higher rate of MACE compared to patients with 1 component (4.4% vs 1.6%; p=0.002), while no difference observed compared to individuals with 2 components (4.4% vs 3.2% p=0.25) of metabolic syndrome. In conclusion, Metabolic syndrome patients have significantly greater prevalence, severity, and prognosis of CAD compared to patients with 1 but not 2 components of metabolic syndrome.  相似文献   

12.
A case-study on 95 inpatients with hydatid disease admitted to a community hospital in Milan is presented. Clinical records from January 1975 through December 1985 were reviewed. Data were analyzed according to: individual characteristics of the subject; previous history of hydatid disease and present signs and symptoms; tests and instrumental examinations performed to ascertain the disease; type of treatment and outcome. Liver (56%) and lung (18%) were the most commonly involved organs, but lung location was, relatively to age, more frequent in children and teenagers than in adults. Intradermal (Casoni) or serological (Ghedini) tests and scintigraphy for the hepatic localization, and lung stratigraphy or histologic section for the pulmonary one, were the most frequent examinations performed. Seventy-three patients (77%) underwent surgical treatment.  相似文献   

13.
To assess the electromyographic (EMG) activation of trunk muscle during exertions performed in one primary plane (sagittal, frontal, transverse), we previously proposed a protocol allowing minimizing out-of-plane efforts (coupled moments – CMs) with the use of a static dynamometer combined with a visual feedback system. The aims of this study were to go further by testing motor learning and reliability issues related to such a protocol. Three identical sessions were conducted, where maximal voluntary contractions and submaximal ramp contractions were performed in six different directions while standing in the dynamometer. Two feedback conditions were tested, the simple 1D-feedback in the primary plane and the full 3D-feedback in all planes simultaneously. Surface EMG signals were collected from back and abdominal muscles and EMG amplitude and CMs were computed during the ramp contractions. Providing a 3D feedback to minimize CMs did not improve EMG reliability or in other words, did not reduce the within-subject variability. Providing three assessment days had practically no effect (no learning) on CMs and EMG variables. Overall, the reliability of EMG was at best moderate. However, although this limits its use on an individual basis, it still allows within- and between-group comparisons for research applications.  相似文献   

14.
《朊病毒》2013,7(4):375-382
Creutzfeldt-Jakob disease (CJD), included in the human transmissible spongiform encephalopathies (TSE), is widely known to be caused by an abnormal accumulation of misfolding prion protein in the brain. Human prion protein gene (PRNP) is mapped in chromosome 20p13 and many single nucleotide polymorphisms (SNPs) in PRNP have been discovered. However, the functionality of SNPs in PRNP is yet unclear, though several SNPs have been known as important mutation related with susceptibility human prion diseases. Our aim is to identify specific genotype patterns and characteristics in the PRNP genomic region and to understand susceptibility among Korean discriminated prion disease patients, suspected CJD patients and the KARE data group. Here, we have researched genotypes and SNPs allele frequencies in PRNP in discriminated prion disease patients group (n = 22), suspected prion diseases patients group (n = 163) and the Korea Association REsource (KARE) data group (n = 296) in Korea. The sequencing regions were promoter region, exon1 and exon2 with their junction parts among 481 samples. A total of 25 SNPs were shown in this study. Nucleotide frequencies of all SNPs are exceedingly tended to bias toward dominant homozygote types except in rs2756271. Genotype frequencies at codon 129 and 219 coding region were similar with previous studies in Korea and Japan. Pathogenic mutations such as 102P/L, 200E/K and 203V/I were observed in discriminated CJD patients group, and 180V/I and 232M/R were shown in suspected prion disease patients group and the KARE data group. A total of 10 SNPs were newly identified, six in the promoter region, one in exon 2 and three in the 3′ UTR. The strong and unique linkage disequilibrium (D' = 0.94, r2 = 0.89) was observed between rs57633656 and rs1800014 which is located in codon 219 coding region. We expect that these data can be provided to determine specific susceptibility and a protective factor of prion diseases not only in Koreans but also in East Asians.  相似文献   

15.
The performance during the preclinical course of 517 students who had applied to this medical school for admission in 1981 and who had been accepted by the school or by another British medical school was analysed in relation to variables measured at the time of application to find factors that predicted success in the preclinical course, whether students chose to take an intercalated degree, and the class achieved in the intercalated degree. Thirty one of the 507 students who entered medical school withdrew from the course or failed their examinations; these students were particularly likely not to have an A level in a biological science. O level grades were of minimal predictive value for performance during the preclinical course. A level grades discriminated between successful and unsuccessful students but had too low a specificity or sensitivity to be of use in individual prediction. Mature entrants performed better overall than school leavers. Background variables accounted for only 14.2% of the variance in performance, implying that motivation and personality may be more important in determining performance. The 80 students who chose to take an intercalated degree were more likely to be men and not to be mature entrants; for a further 50 students intercalated degrees were obligatory. Performance in the intercalated degree related to performance during the preclinical course and to assessments made at the selection interview but not to achievement at O or A level.  相似文献   

16.
The objective of this study was to evaluate if a multi-sensor system (milk, activity, body posture) was a better classifier for lameness than the single-sensor-based detection models. Between September 2013 and August 2014, 3629 cow observations were collected on a commercial dairy farm in Belgium. Human locomotion scoring was used as reference for the model development and evaluation. Cow behaviour and performance was measured with existing sensors that were already present at the farm. A prototype of three-dimensional-based video recording system was used to quantify automatically the back posture of a cow. For the single predictor comparisons, a receiver operating characteristics curve was made. For the multivariate detection models, logistic regression and generalized linear mixed models (GLMM) were developed. The best lameness classification model was obtained by the multi-sensor analysis (area under the receiver operating characteristics curve (AUC)=0.757±0.029), containing a combination of milk and milking variables, activity and gait and posture variables from videos. Second, the multivariate video-based system (AUC=0.732±0.011) performed better than the multivariate milk sensors (AUC=0.604±0.026) and the multivariate behaviour sensors (AUC=0.633±0.018). The video-based system performed better than the combined behaviour and performance-based detection model (AUC=0.669±0.028), indicating that it is worthwhile to consider a video-based lameness detection system, regardless the presence of other existing sensors in the farm. The results suggest that Θ2, the feature variable for the back curvature around the hip joints, with an AUC of 0.719 is the best single predictor variable for lameness detection based on locomotion scoring. In general, this study showed that the video-based back posture monitoring system is outperforming the behaviour and performance sensing techniques for locomotion scoring-based lameness detection. A GLMM with seven specific variables (walking speed, back posture measurement, daytime activity, milk yield, lactation stage, milk peak flow rate and milk peak conductivity) is the best combination of variables for lameness classification. The accuracy on four-level lameness classification was 60.3%. The accuracy improved to 79.8% for binary lameness classification. The binary GLMM obtained a sensitivity of 68.5% and a specificity of 87.6%, which both exceed the sensitivity (52.1%±4.7%) and specificity (83.2%±2.3%) of the multi-sensor logistic regression model. This shows that the repeated measures analysis in the GLMM, taking into account the individual history of the animal, outperforms the classification when thresholds based on herd level (a statistical population) are used.  相似文献   

17.
Traditional breast conservation therapy consists of lumpectomy and whole-breast irradiation. Local recurrence after breast conservation is usually managed with salvage mastectomy. Skin-sparing mastectomy and immediate autologous tissue reconstruction is an accepted method of managing primary breast malignancies with exceptional aesthetic results. The purpose of this study was to evaluate this technique in the previously irradiated breast. This study is a retrospective review of all patients undergoing skin-sparing mastectomy and immediate reconstruction with autologous tissue after failed breast conservation therapy between 1995 and 1999. There were 11 patients with a mean age of 45 years (range, 34 to 58 years). Initial lumpectomy was performed for ductal carcinoma in situ in six patients and infiltrating carcinoma (ductal or lobular) in five patients. The interval from lumpectomy to salvage mastectomy ranged from 12 to 169 months (mean, 44 months). Reconstructive techniques included unipedicled transverse rectus abdominis musculocutaneous (TRAM) flap (n = 4), free TRAM flap (n = 4), and latissimus flap with immediate placement of a saline implant (n = 3). Flap survival was 100 percent, and there were no early flap complications. One patient developed partial-thickness mastectomy flap loss (3 x 3 cm), which was managed conservatively. There were no instances of full-thickness mastectomy skin loss. Late complications included capsular contracture (n = 2), fat necrosis (n = 1), and ventral hernia (n = 1). There was one late death from metastatic disease; the remaining patients were without evidence of disease at a mean of 48 months (range, 30 to 75 months). Aesthetic results were judged as excellent (n = 4), good (n = 5), fair (n = 1), and poor (n = 1). These results demonstrate that skin-sparing mastectomy and immediate autologous tissue reconstruction can be safely performed in patients with previous whole-breast irradiation. Clearly, patient selection is paramount with attention to the quality of the irradiated breast skin and the anatomic location of the recurrent disease. In this experience, the best results were seen after TRAM (pedicled or free) flap reconstruction.  相似文献   

18.
The diagnosis of Crohn''s disease in childhood has been facilitated by the use of fibreoptic endoscopy with biopsies, complemented by double-contrast radiology. Clinical suspicion leads initially to several relevant blood tests. These are followed by endoscopy and multiple colonic biopsies or barium follow-through studies depending on whether large-bowel or small-bowel disease is suspected. The present approach to diagnosis is based on corroborative investigative techniques-endoscopy, radiology, and histology, The availability of paediatric colonoscopes of small diameter should make it possible for paediatricians to perform limited examinations, but when more extensive endoscopy is indicated the child should be referred to special centres.  相似文献   

19.
OBJECTIVE--To determine the association between infection with Helicobacter pylori and dyspepsia. DESIGN--Cross sectional study of dyspeptic subjects and age and sex matched controls identified by a questionnaire survey of all inhabitants aged 20-69. (Endoscopy, histological examination, and microbiological examinations of biopsies from the gastric mucosa were performed blind.) SETTING--Population based survey in Sørreisa, Norway. SUBJECTS--All 782 dyspeptic subjects (excluding those with a previous history of peptic ulcer, gall stones or kidney stones, and coronary heart disease) and controls were offered an endoscopy, of whom 309 dyspeptic subjects and 310 controls attended. MAIN OUTCOME MEASURES--Prevalences of endoscopic and histological diagnoses and of cultures positive for H pylori. RESULTS--A high prevalence of positive cultures, increasing with age, was found in both dyspeptic subjects (48%) and non-dyspeptic controls (36%) (p = 0.004). Positive cultures in both dyspeptic subjects and controls were strongly associated with histological gastritis (70%, 95% confidence interval 65.5 to 85.3; 60%, 52.7 to 67.7, respectively) and peptic ulcer (92%, 61.5 to 99.8; 64.1, 9.4 to 99.2, respectively). Only 3% of subjects with a histologically non-inflamed gastric mucosa had this infection (dyspeptic subjects 2%, 0.2 to 7.0; controls 4%; 1.2 to 8.8). CONCLUSIONS--The relation between dyspeptic symptoms and H pylori is dubious; H pylori seems to have a pathogenetic role in gastritis and may be a contributing factor but not a cause of peptic ulcer.  相似文献   

20.
In an urban general practice serving 7800 patients, all patients presenting over five and a half years with dyspepsia lasting more than two weeks were investigated by fibreoptic endoscopy and cholecystography, and many by barium meal. Of the 393 patients with dyspepsia, 346 completed the investigation: 180 had specific disease of the oesophagus, stomach, duodenum, or gall bladder, including six with carcinoma. Al further 67 had mucosal disease, and only 99 patients had no abnormality. After the first year the number of patients presenting annually and the percentage of patients with specific lesions remained constant. The annual incidence for patients with dyspepsia was about 1% and for patients with specific lesions 0.4%, suggesting that each year those who became symptom free (either spontaneously or because of treatment) were balanced by a similar number who developed symptoms. In contrast to the conclusions of other workers that an "open-access" endoscopy service could not be justified because the number of patients with specific lesins fell during their survey, we suggest that such endoscopy services are indeed worth while for providing an accurate diagnosis of dyspepsia.  相似文献   

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