Abnormalities of the cadherin-catenin complex in chemically-induced colo-rectal carcinogenesis

Beta-Catenin is a multifunctional protein originally identified as a component of the cadherin cell-cell adhesion complex. It also binds the adenomatous polyposis coli (APC) tumour suppressor which controls beta-catenin cellular levels through its degradation. (beta-Catenin and/or APC mutations result in increased cytoplasmic Beta-catenin and nuclear translocation. The aim of the present study was to examine the expression and cellular localisation of alpha and beta-catenin, p120 and E-cadherin in a chemically-induced mouse model of colo-rectal cancer using 1,2-dimethylhydrazine (DMH). Female Balb/C mice were injected subcutaneously with a solution providing 25 mg DMH base/kg body weight for 17 weeks. Animals were killed and tumours identified in the intestine with a dissecting microscope. Formalin-fixed paraffin-embedded sections of normal and dysplastic colonic mucosa were stained by an indirect avidin-biotin immunohistochemical technique using mouse monoclonal antibodies, and membranous, cytoplasmic and nuclear cellular localisation was assessed by light microscopy. Staining distribution scored as follows: 3, > 90 % positive epithelial cells; 2, >50 % positive epithelial cells; 1, <50 % positive epithelial cells. Non-dysplastic colonic epithelial cells revealed beta-catenin expression at the membrane (33/41 scored 3),areas of cytoplasmic expression (24/41 scored 1) and no nuclear staining. Dysplastic colonic epithelium revealed increased membranous and cytoplasmic, beta-catenin immunoreactivity (39/41 and 38/41 both scored 3) with focal nuclear staining (14/41). Expression patterns for ac-catenin, p120, and E-cadherin were similar to beta-catenin with increased membranous and cytoplasmic immunoreactivity in dysplastic mucosa, although no nuclear staining was observed. Increased cytoplasmic expression and nuclear localisation of beta-catenin are consistent with a possible mutation in its gene, and this finding was in keeping with the mutational analysis of exon 3 by single-strand conformational polymorphism. Increased immunoreactivity of the other catenins also suggests further disruption in catenin regulation. In summary, alterations in the beta-catenin expression and cellular localisation in the DMH-induced tumours are similar to those seen inhuman sporadic colorectal tumours. The DMH is therefore a useful model for studying the abnormalities of the E-cadherin-catenin pathway in colorectal carcinogenesis.     

Off-pump coronary artery bypass grafting: not a flash in the pan

During the past decade, technical improvements have made off-pump coronary artery bypass operations a routine procedure. During this time, off-pump coronary artery bypass has been audited against conventional techniques by many observational, case-matched, and prospective randomized studies. There is evidence in the literature suggesting that off-pump coronary artery bypass operations reduce postoperative morbidity, organ dysfunction, and costs, without compromising midterm outcome compared with conventional coronary operations. The available evidence also supports the view that high-risk patients might benefit the most from revascularization on the beating heart. High quality follow-up data are still needed to assess the impact of off-pump coronary artery bypass operations on long-term clinical outcome.     

Postoperative pain as complication of hernia surgical repair with mesh and plug

The authors assess the incidence of locoregional chronic pain after inguinal hernia repair. One hundred consecutive patients, with a mean age of 65.4 years, suffering from primary monolateral inguinal hernia, underwent suture-less mesh-plug hernioplasty. In all cases the inguinal nerves were identified. In the early postoperative period, a questionnaire was given to all patients in order to assess the frequency, type and intensity of postoperative locoregional pain and the impact of the pain on their quality of life. Sixty patients were available for follow-up with clinical examination and these were given the same questionnaire 2-4 years after hernioplasty. Pain intensity was scored by means of a visual-analogue scale (from 0 to 10). The incidence of locoregional pain after hernioplasty was 13.0% in the early postoperative period and 25.0% after a longer period of follow-up. None of the patients presented recurrent hernia. The symptomatic patients reported mild or moderate neurogenic pain. Severe pain was not reported. On the whole, the presence of mild-to-moderate chronic pain had no impact on the patients' quality of life. Our study confirms the high incidence of locoregional chronic pain even after sutureless mesh-plug hernioplasty, but that this has no serious effects on the patients' quality of life.     

Cholelithiasis and renal cysts: simultaneous laparoscopic treatment

Laparoscopic surgery has been increasingly used in different fields of surgery. This report concerns the authors' experience with combined laparoscopic cholecystectomy and symptomatic renal cyst decortication. The mean diameter of the cysts was 11.2 cm. and involved the left and right kidney in 3 and 1 patient, respectively. All cysts were peripheral. Surgery was performed using 4 trocars in 3 cases and 5 trocars in the other. The mean operative time was 110 minutes and mean blood loss 40 cc. Postoperative pain was minimal. The mean duration of postoperative ileus was 2.2 days. No significant complications were observed. The mean postoperative hospital stay was 3.5 days. At follow-up examinations all patients were pain-free. Recurrence of the cyst was observed in only one case. Combined laparoscopic cholecystectomy and renal cyst decortication is technically feasible in selected cases and does not seem to significantly affect the perioperative course of cholecystectomy.     

Muscle metaboreflex-induced increases in stroke volume

PURPOSE: Accumulation of by-products of metabolism within skeletal muscle may stimulate sensory nerves, thus evoking a pressor response named muscle metaboreflex. The aim of this study was to evaluate changes in central hemodynamics occurring during the metaboreflex activation. METHODS: In seven healthy subjects, the metaboreflex was studied by postexercise regional circulatory occlusion at the start of the recovery from a mild rhythmic forearm exercise. Central hemodynamics was evaluated by means of impedance cardiography. RESULTS: The main findings of this study were that, with respect to rest, the metaboreflex: 1) raised mean blood pressure (+13%; P < 0.01); 2) enhanced myocardial contractility (-12% in preejection period/left ventricular ejection time ratio; P < 0.01); 3) prolonged diastolic time (+11%; P < 0.01); 4) increased stroke volume (+ 10%; P < 0.05); and 5) increased cardiac output (+6%; P < 0.05). These responses were present neither during recovery without circulatory occlusion nor during circulatory occlusion without prior exercise. Moreover, the metaboreflex did not affect systemic vascular resistance and induced bradycardia with respect to recovery without circulatory occlusion. CONCLUSION: These results suggest that the blood pressure response during metaboreflex activation after mild rhythmic exercise is strongly dependent on the capacity to increase cardiac output rather than due to increased vascular resistance.     

Analogic versus digital mammographic examination a radiological study of mammary microcalcifications on 52 surgical samples

PURPOSE: Digital mammography is known to have lower spatial resolution compared to conventional analogic mammography. The aim of this study was to evaluate whether this physical feature could compromise the perception of microcalcifications in radiological findings. MATERIALS AND METHODS: Fifty-two surgical samples of non-palpable breast lesions with microcalcifications were imaged using both techniques. The images were examined by four different radiologists. Data processing was limited to comparing the number of microcalcifications found on the conventional and digital images, in both standard and magnified modality. The cases were classified into 3 groups according to the number of calcifications demonstrated in the surgical sample: less than 10, 10 to 30, and more than 30. The differences in the count of microcalcifications with the two acquisition modalities were evaluated with the Kappa test. In order to compare the differences we synthesised by percentage those cases exhibiting a larger or lesser number of calcifications. RESULTS: The Kappa test was 0.546 in standard analogic vs standard digital, 0.582 in magnified analogic vs magnified digital, 0.828 in standard analogic vs magnified analogic and 0.492 in standard digital vs magnified digital. The most significant results were observed on comparing the magnifications produced with the two modalities: in 25% of cases, digital magnification detected more calcifications than did traditional magnification. The number of cases where standard digital images allowed the detection of more calcifications than standard analogic images was significant, although less important (17.8%). CONCLUSIONS: The study was able to provide data that confirm the overall equivalence of the two techniques, as far as subtle mammographic findings (such as microcalcifications) are concerned. In particular, as applied to the series we examined, there is a cautious advantage in favour of the digital technique. More clinical studies, on larger series, will be necessary for a further and more thorough comparison of the two techniques, so that the results might be consistently useful in clinical practice.     

Multislice computed tomography in the preoperative assessment of adult-to-adult living donor liver transplantation: personal results

PURPOSE: To evaluate the possible role of multislice spiral computed tomography (MSCT) as the sole imaging examination in the preoperative assessment of potential donors undergoing adult-to-adult living donor liver transplantation (LDLT). MATERIALS AND METHODS: Fifteen patients underwent MSCT with 0.5-second gantry rotation time. Pre- (4 X 2.5 mm collimation) and post-contrast (4 X 1 mm collimation) acquisitions during arterial and portal venous phases were performed after intravenous administration of 140 ml of non ionic contrast agent at 4-5 ml/s, with a delay time of 25 and 60 seconds, respectively. Pre-contrast scans with 80 and 140 kVp were acquired at the same level used to assess liver density. Real-time interaction with the post-contrast 3D data set was performed on a dedicated workstation to determine total and lobar liver volume, and to assess arterial and venous vascular anatomy. RESULTS: Steatosis was found in three patients, who as a consequence were excluded as possible candidates. MSCT correctly identified five cases of arterial anatomical variations: two cases of the right hepatic artery arising from the superior mesenteric artery, two cases of the common hepatic artery arising from the superior mesenteric artery and one case of the left hepatic artery arising from left gastric artery. In two cases portal trifurcation was considered a criterion for exclusion. A 4% error in the liver volume calculation was found at surgery, in no case considered significant. Two patients underwent surgery and three have been short-listed. CONCLUSIONS: MSCT enables complete preoperative evaluation of potential donors undergoing LDLT. Total and lobar volume determination provided accurate and reproducible information. MSCT enabled correct surgical planning without intra-operative complications. One of the limits of the technique was the poor visualization of the biliary anatomy with the need to perform an intraoperative cholangiography in all the patients.     

Short-term correlations between clinical and MR imaging findings in relapsing-remitting multiple sclerosis

BACKGROUND AND PURPOSE: Despite extensive use of MR imaging to provide markers of multiple sclerosis (MS) activity and accumulated disease burden, the magnitude of the relationship between clinical and MR findings is still debated. Using data from the European/Canadian glatiramer acetate (GA) trial, we investigated short-term correlations between clinical and MR measures of disease activity in patients with relapsing-remitting MS (RRMS). METHODS: In a 9-month, double-blinded, placebo-controlled study, 239 patients with RRMS were randomly assigned to receive 20 mg GA (n = 119) or placebo (n = 120). Clinical assessment included monthly neurologic examinations with Expanded Disability Status Scale scoring and visits for symptoms suggestive of relapse. Dual-echo T2-weighted and pre- and postcontrast T1-weighted brain MR images were obtained at baseline and monthly during follow-up. Contrast-enhancing and new T2-hyperintense lesions were counted, and total T2-hyperintense and T1-hypointense lesion volumes were measured. RESULTS: Significant univariate correlations were found between the number of relapses during the study period and the number of enhancing lesions at baseline (r = 0.25) and during follow-up (r = 0.30) in the study population as a whole. Multivariable analysis showed that two independent factors were more strongly correlated with relapse frequency: the number of relapses during the 2 years before entry and the number of on-trial enhancing lesions, in the whole study population and in the placebo group. CONCLUSION: In RRMS, MR imaging measures of inflammatory activity are modestly but significantly correlated with the occurrence of clinical attacks over the short term. Clinical and MR imaging assessment can provide complementary outcome measures for RRMS trials.