Colorectal cancer in patients under close colonoscopic surveillance

BACKGROUND & AIMS: Colonoscopic polypectomy is considered effective for preventing colorectal cancer (CRC), but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated. We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high-grade dysplasia. METHODS: Patients were drawn from 3 adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. We identified patients subsequently diagnosed with invasive cancer or adenoma with high-grade dysplasia. The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified are described and risks associated with their development explored. RESULTS: CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years (incidence, 1.74 cancers/1000 person-years). The cancers were located in all regions of the colon; 10 were at or proximal to the hepatic flexure. Although most of the cancers (84%) were of early stage, 2 participants died of CRC. Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up. Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia. CONCLUSIONS: CRC is diagnosed in a clinically important proportion of patients following complete colonoscopy and polypectomy. More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed.     

Amidolytic assay of human factor XI in plasma: comparison with a coagulant assay and a new rapid radioimmunoassay

The traditional coagulant assay for plasma factor XI suffers from a relatively high coefficient of variation, the need for rare congenitally deficient plasma, and a poor correlation between precision and sensitivity. We have developed a simple functional amidolytic assay for factor XI in plasma using the chromogenic substrate PyrGlu-Pro-Arg- p-nitroanilide (S-2366). After inactivation of alpha 1-antitrypsin, CI inhibitor, and other plasma protease inhibitors with CHCI3, plasma was incubated with kaolin, in the absence of added calcium, which limited the enzymes formed to those dependent on contact activation. Soybean trypsin inhibitor was used to minimize the action of kallikrein on the substrate. Once the reaction was complete, corn trypsin inhibitor was used to inactive factor XIIa, the enzyme generated by exposure of plasma to negatively charged surfaces, which had activated the factor XI. The assay is highly specific for factor XI, since plasma totally deficient in that zymogen yielded only 1%-3% of the enzymatic activity in normal plasma under identical conditions. The requirements for complete conversion of factor XI to XIa in plasma within 60 min were, respectively, factor XII, 0.6 U/ml, and high molecular weight kininogen, 0.2 U/ml. Prekallikrein was not an absolute requirement for complete activation but did accelerate the reaction. The intraassay coefficient of variation was 3.4%, and the mean of 35 normal plasmas was 1.00 U +/- 0.24 SD. In addition, a new rapid radioimmunoassay was devised using staphylococcal protein A as the precipitating agent for a complex of factor XI antigen with monospecific rabbit antibody. The mean was 1.01 U +/- 0.30 SD. The correlation coefficients for amidolytic versus coagulant and amidolytic versus radioimmunoassay were r = 0.95 for the former and 0.96 for the latter. Thus, a simple, accurate amidolytic assay and a radioimmunoassay have been devised for measuring factor XI in plasma that correlate well with the coagulant activity of factor XI, as determined in our laboratory.     

Clopidogrel administration prior to coronary artery bypass grafting surgery: the cardiologist's panacea or the surgeon's headache?

AIMS: Thrombotic complications after percutaneous coronary intervention procedures have decreased in past years mainly due to the use of clopidogrel antiplatelet therapy. However, the risk of bleeding due to enhanced and irreversible platelet inhibition in patients who will require surgical coronary revascularization instead has not been adequately addressed in the literature. The purpose of this study was to evaluate the effect of pre-operative clopidrogel exposure in haemorrhage-related re-exploration rates, peri-operative transfusion requirements, morbidity, and mortality in patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS AND RESULTS: A study population of 2359 patients undergoing isolated CABG between January 2000 and June 2002 was reviewed. Of these, 415 (17.6%) received clopidogrel prior to CABG surgery, and 1944 (82.4%) did not. A risk-adjusted logistic regression analysis was used to assess the association between clopidogrel pre-medication (vs. no) and haemostatic re-operation, intraoperative and post-operative blood transfusion rates, and multiple transfusions received. Haemorrhage-related pre-operative risk factors identified from the literature and those found significant in a univariate model were used. Furthermore, a sub-cohort, matched-pair by propensity scores analysis, was also conducted. The clopidogrel group had a higher likelihood of haemostatic re-operation [OR = 4.9, (95% CI, 2.63-8.97), P < 0.01], an increase in total packed red blood cell transfusions [OR = 2.2, (95% CI, 1.70-2.84), P < 0.01], multiple unit blood transfusions [OR = 1.9, (95% CI, 1.33-2.75), P < 0.01] and platelet transfusions [OR = 2.6, (95% CI, 1.95-3.56), P < 0.01]. Surgical outcomes and operative mortality [OR = 1.5, (95% CI, 0.36-6.51), P = 0.56] were not significantly different. CONCLUSION: Pre-operative clopidogrel exposure increases the risk of haemostatic re-operation and the requirements for blood and blood product transfusion during, and after, CABG surgery.     

Pressor effect of inhaled ergotamine in orthostatic hypotension

Treatment of orthostatic hypotension due to autonomic failure frequently necessitates use of pressor agents. Because venous pooling contributes significantly to this disorder, the venoconstrictive properties of ergotamine offer theoretical advantages over pure arteriolar pressor agents. However, the low and erratic bioavailability of oral preparations has hindered the use of ergotamine. Accordingly, the efficacy of inhaled ergotamine tartrate (1 puff, 0.36 mg) was compared to placebo in 8 patients with severe autonomic failure. Blood pressure was monitored in the seated position with an automated device. Ergotamine produced significant increases in systolic (29 +/- 5 mm Hg, p less than 0.01 by analysis of variance) and diastolic (13 +/- 1 mm Hg, p less than 0.001) blood pressures compared to placebo (-9 +/- 5 and -2 +/- 3, respectively). Upright blood pressure 2 hours after administration was significantly greater with ergotamine (119 +/- 8/69 +/- 6 mm Hg) vs placebo (82 +/- 7/59 +/- 5 mm Hg, p less than 0.05). Motionless standing time, a measurement of functional capacity, also improved with ergotamine (200 +/- 58 vs 85 +/- 22 seconds). No side effects were noted, but patients with coronary or peripheral artery disease were excluded. Inhaled ergotamine may provide an effective and practical therapy for disabling orthostatic hypotension due to autonomic failure.     

Just noticeable difference in perception of physical exertion during cycle exercise in young adult men and women

The purpose of this investigation was to describe the just noticeable difference (JND) in perceived exertion during cycle exercise. Males (n = 20) and females (n = 26) (21.4 ± 3.1 year) performed load-incremented cycle exercise to peak intensity. At the end of each minute, subjects rated their overall-body perceived exertion using the OMNI (0–10) rating of perceived exertion (RPE) scale. Individual regression derived the power output (PO) corresponding to RPE 5. This PO served as the standard stimulus (SS). On a separate occasion, four 5-min cycling bouts were performed with 5 min rest between bouts. During bouts 1 and 3 subjects cycled at the SS. During bouts 2 and 4 subjects adjusted the resistance to achieve a level of exertion just noticeably above/below the SS. The difference in final 30-s oxygen consumption (VO₂) and PO between each JND bout and the previous SS were the above (JND-A) and below (JND-B) perceived exertion JNDs. JND-A and JND-B were compared between genders and between subjects exhibiting lower versus higher ventilatory threshold (VT) and VO_2PEAK within genders for VO₂ (l·min^?1, %VO_2PEAK) and PO (W, %SS). JND-B was significantly (P < 0.05) greater than JND-A for VO₂ and PO, when expressed in absolute (l·min^?1, W) and relative units (%VO_2PEAK, %SS). Males exhibited greater JND values than females in absolute, but not relative, units. Subjects with lower and higher VT and VO_2PEAK exhibited similar JND values. The JND can serve as an effective tool to measure perceptual acuity and to determine individual ability to self-regulate prescribed exercise intensities.     

From guidelines to standards of care for open tibial fractures

IntroductionThe standards for the management of open fractures of the lower limb published by the British Association of Plastic, Reconstructive and Aesthetic surgeons (BAPRAS) and British Orthopaedic Association (BOA) were introduced to improve the treatment received by patients after open injury to the lower limb. These Standards were released after BAPRAS/BOA published Guidelines for the management of open tibial fractures.MethodsWe wished to determine the impact of these Standards upon the surgical management of open tibial fractures by comparing patients admitted to an orthoplastic centre in the 45 months concluding December 2009 (the Guidelines era) with those admitted during 2011 (the Standards era). Surgical procedures required during the first 30 days and 12 months after injury were determined. Cases were divided into ‘directly admitted patients’ (DAP) and ‘transferred patients’ (TP). Standards-era patients were divided further into those who had surgery exclusively at the orthoplastic centre (orthoplastic patients (OPP)) and those transferred after surgery (TASP).ResultsThe number of TP trebled in frequency in the Standards era, 25% of whom were transferred before surgery. Significantly fewer surgical procedures were required for DAP and OPP groups compared with TP (and TASP) groups in both eras (Mann–Whitney U-test, p=0.05). DAP and OPP groups during the Standards era underwent the fewest procedures, with the vast majority of cases treated with two or fewer procedures in the first 12 months (88% and 80%, respectively, compared with 61% in the Guidelines era). In the Guidelines era, 44% of TP cases and in the Standards era 39% of TP and 29% of TASP groups underwent two or fewer procedures.Approximately two-thirds of open tibial fractures managed in our orthoplastic centre were patients transferred after surgery. The greatest impact of the Standards was evident for those who underwent surgery exclusively in the orthoplastic centre, reflecting a more deliberate combined strategy.ConclusionThese findings vindicate the Standards as well as mandating reorganisation and resourcing of orthoplastic services to ensure immediate transfer and early combined surgery. By increasing the capacity to deal with time-dependent initial surgery, the surgical burden that the patient must endure, and which the service must provide, are reduced.     

A regulated RNA binding protein also possesses aconitase activity.

A clone for the iron-responsive element (IRE)-binding protein (IRE-BP) has been transfected and expressed in mouse fibroblasts. The IRE-BP gene product binds IREs with high affinity and specificity. Amino acid alignments reveal that the IRE-BP is 30% identical to mitochondrial aconitase. The 18 active site residues of mitochondrial aconitase are identical to those in the IRE-BP, suggesting that the IRE-BP may possess aconitase activity. After purification of native IRE-BP and immunoaffinity purification of transfected and expressed IRE-BP, we demonstrate that the purified IRE-BP has aconitase activity.