Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

Faecal occult blood test‐based screening programme with high compliance for colonoscopy has a strong clinical impact on colorectal cancer

Background:

The results of a pilot colorectal cancer screening programme by biennial immunochemical faecal occult blood test (FOBT) are reported.

Methods:

All residents aged between 50 and 69 years in the Italian province of Lecco were invited to have a FOBT. Those with a positive result were offered colonoscopy. FOBT uptake and compliance with colonoscopy were assessed. Detection rate and positive predictive value (PPV) for cancer and adenoma were calculated. Tumour stages were compared between screen‐detected cancers and other colorectal cancers diagnosed within the target age group.

Results:

Some 38 693 (49·6 per cent) of 78 083 individuals had a FOBT and 2392 (6·2 per cent) had a positive result. Colorectal cancer was diagnosed in 4·6 per cent and advanced adenoma in 32·7 per cent. PPVs were 4·0 per cent for cancer, 28·1 per cent for advanced adenoma and 36·6 per cent for any adenoma. There was a significant difference in incidence of stage III/IV disease between screened and non‐screened cohorts. Compliance for colonoscopy was 92·0 per cent. Major determinants of compliance were age less than 59 years, female sex, high education level and non‐manual work.

Conclusion:

These results justify extension of colorectal cancer screening to other regions of Italy. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Calcium entry blockers and cardioplegia: interaction between nifedipine, potassium, and hypothermia

The potential additive protective effect provided by nifedipine to the University of Alabama Hospitals cardioplegia solution (ACS) was assessed with the use of a guinea pig heart-lung model of cardiopulmonary bypass and ischemic arrest. The addition of nifedipine consistently enhanced the protective properties of ACS infused at 37 degrees C; functional recovery was similar to that observed with cold ACS. Despite the additional protection under normothermic conditions, nifedipine did not improve recovery after infusion at 4 degrees C. The abolition by hypothermia of the protective effects of nifedipine suggests a similarity in action between nifedipine and hypothermic protection. The interaction between ACS and nifedipine was studied on bovine coronary arteries in vitro. Nifedipine caused a marked reduction in the coronary vasoconstricting effect of ACS, both under normothermic and hypothermic conditions. The use of nifedipine in cardioplegia may provide additional protection when uneven distribution of the cardioplegic solution is expected and hypothermic protection is unreliable.     

Use of carbon fibers for repair of abdominal-wall defects in rats

Carbon in the form of 8-micron fibers induces growth of connective tissue. The purpose of this study was to measure and histologically characterize tissue ingrowth occurring in carbon fibers implanted for up to 12 months in abdominal-wall defects in rats, compared with polypropylene mesh. Carbon fibers induced significantly more tissue ingrowth than polypropylene mesh at 6 to 12 months postoperatively. The predominant tissues associated with carbon fibers and polypropylene mesh were dense connective tissue and fat, respectively. Fragmentation of the implants did not occur, and implant debris was not found in the regional lymph nodes. Carbon fibers are potentially useful for reinforcing abdominal-wall defects.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Muscarinic modulation of endogenous noradrenaline release from adrenergic terminals in the guinea-pig colon

1 The present study examined the role of muscarinic receptors in the modulation of noradrenaline (NA) release in the guinea-pig isolated distal colon. The spontaneous endogenous NA overflow assayed by HPLC-ED was taken as an index of NA release from enteric noradrenergic nerve terminals. 2 Physostigmine (10 μm ) significantly enhanced spontaneous endogenous NA overflow. Hyoscine (muscarinic antagonist), (R)-(-)-trihexyphenidyl and telenzepine (M₁-selective antagonists), and 11[[2-[(diethylamino)methyl]-1-piperydil]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116, M₂-selective antagonist) inhibited NA overflow in a concentration dependent manner, with the following EC₅₀ values: 131.74 (18.19–953.96), 101.62 (58.83–175.60), 150 (60–330), 30 (5–170) nm , respectively. 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M₁- and M₃- selective antagonist) had no significant effect up to 100 μm . 3 The muscarinic agonist oxotremorine inhibited NA overflow in a concentration dependent manner, with an EC₅₀ value of 0.67 (0.30–1.51) μm . The response to oxotremorine was inhibited by muscarinic antagonists with the following order of potency: hyoscine = (R)-(-)-trihexyphenidyl = telenzepine > 4-DAMP >> AF-DX 116. 4 In the presence of 3 μm tetrodotoxin (TTX), the effect of oxotremorine and 4-DAMP was unchanged, while hyoscine, (R)-(-)-trihexyphenidyl, telenzepine and AF-DX 116, instead of inhibiting, significantly enhanced NA overflow. 5 The present results indicate that, in the guinea-pig colon, endogenous acetylcholine sustains spontaneous NA release by activating muscarinic receptors possibly located on interneurones. In addition, inhibitory muscarinic receptors may exist on adrenergic terminals.     

Palliation of cardiac malformations associated with right isomerism (asplenia syndrome) in infancy

Right isomerism is characterized by the combination of an obstructed pulmonary outflow tract and a total anomalous pulmonary venous connection (TAPVC), which is obstructed in nearly half of the patients. Fourteen patients less than 2 years of age with right isomerism have been seen in our unit. Thirteen of them underwent palliation consisting of a systemic-pulmonary shunt (10 patients) or a combination of shunt and TAPVC repair (3). There were 7 hospital deaths (54%). The presence of obstructed pulmonary venous drainage was the major risk factor in the surgical treatment of these complex cardiac anomalies (p less than .02). Guidelines for the palliative management of right isomerism are suggested.