Abstract Bromocriptin (CB 154) has been found to suppress established lactation at a time when human plasma prolactin (HPRL) concentrations have already returned to the nonpregnant range. This action is due to inhibition of prolactin from the pituitary. It was then thought that a similar degree of inhibition induced during the menstrual cycle may help to uncover other possible biological actions of prolactin. In an attempt to elucidate this question eight breast-feeding mothers and seven normally menstruating volunteers underwent treatment with CB 154, including blood sampling during a sleep period. The dosage was 1 mg., three times daily, for 14 days in the first group and for a whole cycle in the normal volunteers. A control cycle preceded drug administration in the latter group. Prolactin (HPRL), growth hormone (HGH), luteotropin (LH), progesterone (PG), and estradiol (E 2 ) were estimated (mean ± standard error) along the menstrual cycles in the normal volunteers. HPRL and milk volumes were measured in the breast-feeding women in the base-line period and during treatment. In the postpartum group, basal HPRL had already reached normal levels prior to therapy (10.8 ± 1.0 ng. per milliliter) and was significantly (p
Adolescents making the transition to college should have a thorough medical evaluation during the year prior to matriculation. In addition to required and recommended immunizations and tests, a comprehensive history and physical examination is important. Screening for substance abuse, sexual activity, depression, and suicidality is needed with appropriate anticipatory guidance, examinations, and treatment, if indicated. The teen should also be counseled on stress, sleep, and self-care, with information on when to seek medical care. The adolescent should be encouraged to continue communications with the primary care clinician during college. While respecting the adolescent's confidentiality, it is important that the physician communicate all significant medical and psychiatric health information to the college health center before the adolescent arrives on campus.
Radiological techniques have been used to diagnose colorectal cancer (CRC) for over 100 years 1, 2. With the advent of CT scanning 3, radiologists were able to both detect and stage CRC reliably, particularly by insufflating gas to distend the bowel and improve tumour visualization 4, 5. However, it was a far more flamboyant development that truly ignited wider interest. Inspired by flight simulator computer games 6, Dr David Vining fused three-dimensional (3D) data from newer helical CT scanners 7 with virtual reality computer modelling to create a ‘virtual colonoscopy’, allowing radiologists to ‘fly through the body’. The resulting images (of a particularly tolerant colleague, Dr David Gelfand) were presented to the radiological and gastroenterological communities as a 3D rendered video to the sound of Wagner's ‘Flight of the Valkyries’, and CT colonography (CTC) as recognized today was born 8. Accelerated by early reports of excellent diagnostic performance 9, 10, the technique disseminated rapidly, driven by vast improvements in CT scanning hardware and image reconstruction software. Currently, over 100 000 CTC examinations are performed each year in England alone 11. In this article, we describe the modern practice of CTC, what it entails for patients undergoing the test, its diagnostic performance, its main benefits and downsides and specific aspects relevant to early diagnosis of colonic neoplasia. CTC comprises three key aspects: (a) some form of bowel ‘preparation’ (not necessarily involving purgation); (b) colonic gas insufflation; and (c) image acquisition in more than one patient position 12. Most would now regard oral contrast administration, to label or ‘tag’ any residual stool, as an essential prerequisite for competent practice 12. It is this aspect of CTC that precipitates more confusion among clinicians and patients than any other. Faecal tagging is a fundamental aspect of modern CTC and must always be administered, whereas cathartics can be reduced or even omitted entirely in some cases (Fig. 1) 13. The confusion arises because the most commonly used faecal tagging agent, Gastrografin (sodium diatrizoate/meglumine diatrizoate, Bayer plc, Newbury, UK), also has a laxative effect, thereby providing a convenient and simple means to both cleanse and tag the colon using a single agent. Patients must still be warned that they may experience abdominal cramping and diarrhoea 14, 15 and that a tube will be inserted into their rectum through which gas (almost always carbon dioxide, at least in the UK) will be machine-insufflated 16. Scans are performed with the patient supine and prone (or using decubitus positioning if preferred or limited by patient mobility) to allow redistribution of insufflated gas and any retained fluid or stool, thereby improving visualization of the entire circumference of the colonic surface. Nonetheless, CTC can be employed reliably in the older, frailer patient; the average age of patients having CTC in England is over 70, and a quarter are over 80 11. Despite this, serious complications are rare 17, 18 and the procedure is extremely well tolerated and safe 19, 20. Considerable research efforts have been concentrated on establishing the diagnostic accuracy of CTC. The literature is relatively clear regarding detection of established CRC: two meta-analyses have shown that CTC is approximately 96% sensitive for CRC 21, 22, not significantly different from colonoscopy, which was 95% sensitive in one of these analyses 22. Furthermore, a recent further systematic review has shown that identification of (initially undetected) CRC in the 3-year period following CTC is rare, only occurring in 4.4% of cases 23. Since adenomas typically take many years or even decades to transition to carcinoma 24, these are likely to be due to missed CRC at the index CTC examination, entirely consistent with approximately 95% sensitivity for cancer. Regarding large (1 cm+) polyps, CTC correctly identifies approximately 85–90% of individuals with at least one such polyp (i.e. per patient sensitivity) 21, 25 and approximately 75–80% of any given 1 cm+ polyp (i.e. per polyp sensitivity) 8, 25. The discrepancy is because individuals may have multiple 1 cm+ polyps; finding only one of these is enough to define a CTC examination as positive, even if other polyps are missed. Therefore, per polyp sensitivity is (by definition) lower than per patient sensitivity. Small (6–9 mm) polyps are more difficult to detect at CTC, with per patient and per polyp figures of 70–80% 3, 8 and 60–70% 21, 25, respectively. Clearly, the remit of the SPECC (significant polyps and early colorectal cancer) programme is to improve detection and management of significant polyps and early cancers – implying an emphasis on larger lesions which are more likely to be histologically advanced. Therefore, it is particularly relevant that a UK pragmatic randomized trial, SIGGAR, found no significant difference in detection rates of a composite end-point of CRC and large (1 cm+) polyps between colonoscopy and CTC 26. Although the diagnostic accuracy data outlined above show that CTC has excellent diagnostic sensitivity on average, early cancers may be harder to detect. This might mean that, for SPECC in particular, the performance of CTC might be poorer than the meta-analyses and randomized trial outlined above, which derive from ‘all-comers’ and focus on cancer. Perhaps the most pertinent data for early lesions derive from screening populations, since asymptomatic individuals have earlier stage tumours 27. Both UK and US data show that screen-detected cancers are smaller, less bulky and subjectively less conspicuous at CTC than those presenting with colorectal symptoms 28, 29. Does this mean they are more likely to be missed at CTC? Most studies would suggest not. The largest cohort series from asymptomatic individuals undergoing screening found that CTC was again over 90% sensitive for 1 cm+ polyps 30, 31. Furthermore, in a Dutch randomized screening trial of CTC versus colonoscopy 32, initial screening colonoscopy detected more advanced neoplasia on a per attendee basis (although the two were equal on a per invitee basis, due to superior uptake of CTC), which was largely because small (6–9 mm) polyps found at index CTC were not resected immediately but instead kept under follow-up. Once these were included, CTC outperformed colonoscopy on a per invitee basis and was its equal on a per attendee basis 33. Therefore, it is unlikely that SPECC lesions harbour particular problems for detection by CTC. The serrated pathway is increasingly recognized as an important route to colorectal carcinogenesis, estimated to account for 20–30% of CRCs 34. Historically, flat or nonpolypoid lesions have been regarded as an ‘Achilles heel’ for CTC, with fewer than half detected at CTC in some early studies 35, 36. This is, at least partly, because of under-recognition of their existence and clinical importance during the early years of CTC development. Just as Western endoscopists had to adapt and improve detection of serrated neoplasia in response to the experience of Japanese endoscopists 37, a similar adaptation is needed by CTC radiologists. The issue is not purely due to obsolete technology – even with modern equipment, the recent Japanese national CTC trial reported only a 65% sensitivity for 1 cm+ nonpolypoid neoplasms (versus 90% for 1 cm+ neoplasia overall)38. Furthermore, there was a significantly lower detection rate of high-risk (large or histologically advanced) serrated polyps in the Dutch randomized screening trial 39. However, with optimized technique and image scrutiny, flat polyps can be depicted by CTC. For example, reanalysis of the images from the US multicentre ACRIN 6664 screening trial showed that most flat polyps were reliably visible in retrospect, with the same sensitivity as polypoid lesions 40. There are clear cues to help detection of serrated neoplasms at CTC, in particular surface coating by oral contrast tagging material 41, 42. There is no doubt that serrated neoplasms can be extremely challenging for CTC, but with meticulous attention to patient preparation, colon distension and image scrutiny, these neoplasms can be detected (Fig. 2) 43. Although rarely confused with a SPECC lesion, diminutive polyps (i.e. 5 mm or less) nonetheless present a dilemma to both radiologists and referring clinicians. This is not usually problematic, as CTC has <50% sensitivity for these polyps. However, there is conflicting guidance regarding what to do when a diminutive polyp has been identified by a meticulous radiologist. Some authorities recommend that radiologists should report diminutive lesions if they are seen with confidence (and particularly if multiple)12, whereas others argue that they should be ignored 44. One major difficulty with referring all patients with diminutive polyps for colonoscopy is that CTC has very poor specificity for neoplasia at this size: most such ‘polyps’ will either be hyperplastic (and therefore clinically irrelevant) or false positives 45, meaning the patient is subjected to endoscopy for no ultimate benefit. For example, in one series the false-positive rate fell from 12% to only 4.2% when a 5 mm+ reporting threshold was adopted 46. It is important to recall that the clinical risk of diminutive polyps is small; indeed, the risk of advanced neoplasia in patients in whom their largest polyp is <5 mm is below 4% 47, little over half that of an individual with average risk undergoing screening 48. The risk of high-grade dysplasia or carcinoma, arguably the most important aspects of advanced neoplasia, is even smaller, at 0.7% 47. Therefore, even if diminutive polyps are not reported, an otherwise normal CTC means that the patient has been successfully stratified as lower risk than a randomly selected member of the screening-age population. In our opinion, it makes no logical sense to refer these individuals for endoscopy – colonoscopic capacity is finite, and would be better used to improve provision for higher-risk individuals (e.g. those testing positive in the Bowel Cancer Screening Programme). We should avoid the perverse situation whereby the person accompanying the patient with a diminutive polyp on CTC to the hospital for endoscopy has a higher risk of advanced neoplasia than the patient scheduled for endoscopy. Furthermore, such an over-conservative referral threshold hugely increases healthcare costs and has extremely poor cost-effectiveness, estimated at over $460 000 per life-year gained in one US analysis, which is well over the commonly applied thresholds in the UK 49, 50. As the preceding paragraphs emphasize, CTC is primarily regarded as a tool for detection of colorectal neoplasia rather than lesion characterization. However, there are important morphological clues that may aid in therapeutic decision-making beyond the obvious ability of CTC to depict remote metastases. For example, CTC can reliably determine when a carcinoma is not an early lesion, for example transgressing the muscularis propria (denoting a T3 stage) and therefore unequivocally requiring full oncological resection (or palliation). Indeed, systematic review shows that studies in which the colon was distended with rectal contrast (whether using gas or positive iodinated contrast medium) reported more accurate T staging than those in which conventional, unprepared CT was performed 51. More subtly, the shape of a CTC-detected mass can help distinguish between T1 and T2 CRCs; the former being arc-shaped and the latter square or trapezoidal 52, although the reliability of this distinction is imperfect. Just as endoscopists recognize the importance of the Paris classification in their overall assessment of the risk of high-grade dysplasia or submucosal invasion (i.e. carcinoma) in any given lesion, CTC permits radiologists to provide useful morphological characterization using the same descriptors. For example, a large Australian study identified polyp morphology (Paris classification 0–IIa+IIc), nongranular surface and Kudo pit pattern type V as being risk factors for invasive cancer 53: of these three parameters, CTC can provide two (clearly it is unable to resolve the pit pattern), and radiologists should be encouraged to record this in their clinical reports (Fig. 3) 54. Although management will ultimately be determined by the colonoscopic assessment, a detailed description at CTC permits the endoscopist to be forewarned of what they are likely to find and so tailor their approach (e.g. ensuring availability of an experienced interventional endoscopist with access to sufficient time in the endoscopy room, their best available endoscopic equipment and optimized patient preparation). CTC is widely used, with excellent diagnostic accuracy for clinically relevant polyps, and provides an alternative means of whole-colon investigation for many patients, particularly those less able to tolerate optical colonoscopy. Serrated polyps and diminutive lesions need careful handling, but with close dialogue between colonoscopists and radiologists, the two tests can be employed in complementary fashion. Radiologists should be encouraged to provide as much morphological information as possible, particularly for larger SPECC lesions, thereby helping assist precolonoscopic risk stratification and procedural planning.
Abstract Aim Obstructed defaecation syndrome is a common condition of multifactorial aetiology and requires specialized evaluation. Accurate and reproducible pelvic floor imaging is imperative for multidisciplinary decision‐making. Evacuation proctography ( EP ) and magnetic resonance defaecography ( MRD ) are the main imaging modalities used to assess dynamic pelvic floor function. The aim of this prospective study was to compare the findings and acceptability of MRD and EP in the same cohort of patients. Method This was a prospective comparative study of MRD vs EP in 55 patients with obstructed defaecation syndrome in a single National Health Service Foundation Trust. Results Fifty‐five patients were recruited and underwent both EP and MRD . Detection rates for rectocoele were similar (82% vs 73%, P = 0.227), but EP revealed a significantly higher number of trapping rectocoeles compared to MRD (75% vs 31%, P < 0.001). EP detected more rectal intussusceptions than MRD (56% vs 35%, P = 0.023). MRD appeared to underestimate the size of the identified rectocoele, although it detected a significant number of anatomical abnormalities in the middle and anterior pelvic compartment not seen on EP (1.8% enterocoele, 9% peritoneocoele and 20% cystocoele). Patients achieved higher rates of expulsion of rectal contrast during EP compared to MRD , but this difference was not significant (76% vs 64% in MRD , P = 0.092). Of the two studies, patients preferred MRD . Conclusions MRD provides a global assessment of pelvic floor function and anatomical abnormality. MRD is better tolerated by patients but it is not as sensitive as EP in detecting trapping rectocoeles and intussusceptions.
Consolidating unbiased, peer-reviewed information from many sources, this book provides a one-stop resource on the use and health benefits of 50 different herbs.While the use of herbs and herbal supplements seem an attractive alternate to man-made therapies, such use is often inspired by anecdotal evidence rather than sound clinical research. Healthy Herbs: Fact versus Fiction examines the health claims associated with 50 popular herbs and coalesces the clinical findings on these natural substances. This useful resource examines the history and use of herbs and will ultimately help readers make informed decisions regarding these natural therapies.The findings in the book are culled from credible sources such as international, peer-reviewed journals, providing nomenclature, history, common usage, effectiveness, and additional suggested reading on selected herbs and herbal supplements. Rather than advocating for or against alternative medicine or herb use, the book provides authoritative, unbiased, and evidence-based information so the health conscious can make informed decisions for themselves.
