A review of the usefulness of D-Dimer in the diagnosis of pulmonary embolism

Pulmonary embolism is a potentially fatal condition that is extremely difficult to accurately diagnose clinically, usually relying on radiological investigations to make the diagnosis. These confirmatory tests are expensive, time consuming and may be associated with considerable morbidity. Thus, the utility of a blood test that reliably makes or refutes the diagnosis is apparent. Most blood tests involve the later stages of thrombolysis. Of these, the D-Dimer tests are the most sensitive, and when combined with monoclonal antibody technology, are of clinical value. Enzyme-linked immunosorbent assay D-Dimer tests have good sensitivity (95%) and moderate specificity (30–45%), but technical considerations prevent their routine use. Latex agglutination tests overcome these technical problems, but their sensitivity is variable (46–100%). Two recently introduced tests show promise. The NYCO-CARD D-Dimer test is a semiquantitative modified enzyme-linked immunosorbent assay test. Relatively few clinical studies have been performed and further validation studies are required. The SimpliRED D-Dimer test uses a new bispecific antibody technique, allows bed-side testing, and has good sensitivity (84–100%) and negative predictive values (92–99%). These tests could be used to screen low risk patients, thus avoiding ventilation-perfusion scans, or in combination with ventilation-perfusion scans and lower limb studies to avoid angiograms in intermediate probability pulmonary embolism patients. Future research will define where these tests show greatest utility, particularly in which patient subgroups, or symptom time intervals.     

The chances that an emergency physician will demonstrate three abdominal aortic aneurysms by ultrasound in the emergency department for credentialing: A statistician's view

The Australasian College for Emergency Medicine requires 15 proctored examinations of the aorta for credentialing in ultrasonography for abdominal aortic aneurysm (AAA). Furthermore, at least three examinations need to be positive for an aneurysm. In the ED where AAA presentations are sporadic, what are the chances that an emergency physician (EP) will have the opportunity to demonstrate three AAAs in the next 12 months? The probability of an event occurring within a given time‐frame can be modelled by the Poisson distribution. Central to the Poisson distribution is the infrequency of the event such as encountering an AAA in the ED. An EP working 30 clinical hours/week in our tertiary‐referral hospital ED can be expected to encounter 15.6 (3.6 symptomatic + 12 asymptomatic) AAA in the next 12 months. The probability of seeing three or more cases during this time is 99.9%. Assuming a proctor can be found for half the cases, the probability of an EP performing proctored ultrasound examinations in at least three AAAs is 98%. This probability drops to 89% if a proctor can be found for only one‐third of cases. For an EP to be almost 100% certain of meeting the credentialing requirements, he/she would need almost 10 proctored ultrasound cases of AAA to be available within his/her shifts during the year. The Poisson distribution has enabled us to model the probability of encountering a given number of AAA in the ED. Analysis such as this may help rationalise the numbers needed for credentialing.     

Capsule enteroscopy and radiology of the small intestine

In a very few years, the video capsule for small bowel enteroscopy has gained widespread clinical acceptance. It is readily ingested, disposable, and allows for a complete, low-invasive endoscopic examination of the entire mucosa of the small bowel. It is a patient-friendly method and a first-line procedure in the difficult evaluation of obscure gastrointestinal bleeding. It has the highest proven figure of diagnostic sensitivity for detecting lesions of the mucosa, irrespective of aetiology. The limitations of capsule endoscopy include difficulty in localising mucosal lesions anatomically and its restricted use in patients with dysphagia, strictures or motor dysfunction. Strictures, transmural and extra-mural lesions in patients with small bowel Crohn’s disease are evaluated by MRI- enterography and CT-enterography.     

Extended long-term culture reveals a highly quiescent and primitive human hematopoietic progenitor population

Long-term culture-initiating cells (LTC-IC) are hematopoietic progenitors able to generate colony-forming unit-cells (CFU) after 5 to 8 weeks (35 to 60 days) of culture on bone marrow (BM) stroma and represent the most primitive progenitors currently detectable in vitro. We have recently reported that long-term cultures initiated with CD34+CD38- cells from BM or cord blood are able to continue generating CFU for at least 100 days, ie, beyond the standard LTC-IC period. In this report, single-cell cultures from cord blood and retroviral marking of cord blood and BM were used to study whether the subpopulation of CD34+CD38- cells able to generate CFU beyond 60 days ("extended long-term culture-initiating cells" or ELTC-IC) are functionally distinct from LTC-IC in terms of timing of initial clonal proliferation and generative capacity. All cord blood LTC-IC formed clones of greater than 50 cells by day 30. In contrast, cord blood ELTC- IC proliferated later in culture, 50% forming clones after day 30. Although efficient retroviral marking of LTC-IC was seen (25% to 45%), marking of ELTC-IC was inefficient (< 1%), consistent with a more quiescent progenitor population. There was a positive correlation between time of clonal proliferation and generative capacity. ELTC-IC generated threefold to fourfold more progeny than did LTC-IC (P < .002). These studies show that there is a functional hierarchy of progenitors in long-term culture which correlates with their level of quiescence. By extending the LTC-IC assay, a more primitive progenitor may be studied that may be functionally closer to the human long-term repopulation stem cell in vivo.     

Reliability of routine double contrast examination of the large bowel: a prospective study of 2590 patients.

A total of 2590 consecutive patients referred for double contrast examination (DCE) of the large bowel were followed up radiographically, clinically, endoscopically, and histopathologically during a four year period. The patients were put into two groups on the basis of the presence or absence of radiographic evidence of colonic disease at the first--that is, index examination. By comparing the findings obtained at the index double contrast examination with those obtained during follow up, the sensitivity, specificity, and accuracy of the index double contrast examination were all calculated at 0.84. The predictive value of a positive report was 0.93 and that of a negative report 0.70. If, however, patients with normal double contrast examinations at the start of this series and not examined further during the follow up period were accepted as free from significant colonic disease, the predictive value of a negative report increased to 0.93. Double contrast examination is thus a reliable method for showing the presence of colonic lesions and therefore considerably helps the management of a given case.     

Flat and depressed colorectal tumours in a southern Swedish population: a prospective chromoendoscopic and histopathological study

BACKGROUND: Flat and depressed colorectal tumours are common in Japan but are very rare or non-existent in Western countries. AIMS: To study the occurrence of flat colorectal tumours in a southern Swedish population. METHODS: In this prospective study, 371 consecutive European patients were examined by high resolution video colonoscopy combined with chromoendoscopy. The nature of the lesions was determined by histopathological examination. RESULTS: A total of 973 tumours were found; 907 (93.2%) were protruding and 66 (6.8%) were flat or depressed. Of the flat/depressed tumours, five (7.7%) were early adenocarcinomas infiltrating the submucosa. Eleven carcinomas (1.2%) were found among protruding tumours. High grade dysplasia was observed in 18% (n=11) of flat/depressed adenomas in contrast with 7.3% (n=65) of protruding adenomas, and occurred in smaller flat/depressed tumours compared with protruding ones (mean diameter 8 mm v 23 mm, respectively). Furthermore, high grade dysplasia was significantly more common in flat elevated tumours with central depression or in depressed adenomas (35.7%; 5/14) than in flat elevated adenomas (12.8%; 6/47). CONCLUSION: Flat and depressed tumours exist in a Western population. Future studies should address whether or not chromoendoscopy with video colonoscopy is necessary in the search for flat colorectal neoplasms.     

Gastroduodenal Tolerance of 75 mg Clopidogrel versus 325 mg Aspirin in Healthy Volunteers: A Gastroscopic Study

Background: Clopidogrel is a new antiplatelet agent that offers increased protection over aspirin in preventing vascular ischaemic events in patients with symptomatic atherosclerosis. In a large, randomized, international study of clopidogrel and aspirin (n = 19,185 patients) clopidogrel was associated with a lower incidence of gastrointestinal adverse events, including gastrointestinal haemorrhage and hospitalizations because of gastrointestinal haemorrhage. The aim of the study was to determine whether macroscopic differences in the gastric mucosa between aspirin- and clopidogrel-treated subjects could be detected by gastroscopy after short-term treatment. Methods: Thirty-six healthy volunteers were randomized in a double-blind, double-dummy, parallel design, to 75 mg/day of clopidogrel or 325 mg/day of aspirin for 8 days. Gastroscopy was performed at base line before administration of study drug and directly after treatment completion. Gastroduodenal effects were measured in accordance with a modified Lanza scale. Results: At base line no difference between the groups was detected (median Lanza score, 0.0 in both groups). At the end of treatment the aspirin group showed a median score of 7.5, and the clopidogrel group showed an unchanged median score of 0.0 (P &lt; 0.001). In the aspirin group 13 individuals reported 19 adverse events versus 8 individuals and 13 adverse events for clopidogrel, with approximately half of the adverse events being gastrointestinal in each group. No serious adverse events were reported. Conclusion: In contrast to aspirin, short-term treatment with clopidogrel does not induce macroscopic changes in the gastroduodenal mucosa. The study results show that in patients without gastroduodenal disease clopidogrel, but not aspirin, does not induce any gastroscopically evident erosions during short-term treatment.