Systemic coronary surgery in the beating heart. Experience in 250 cases

OBJECT: To report our recent experience with off-pump coronary artery revascularization in multi-vessel disease. METHODS: Between October 1996 and August 1998, 250 off-pump (OP) procedures were completed at the Montreal Heart Institute, representing more than 90% of all procedures done during the same time frame (97% for 1998). These patients have been compared to 1870 patients operated upon under cardiopulmonary bypass during the years 1995-1996 (CPB). RESULTS: Mean age, sexe distribution, and preoperative risk factors were comparable for both groups. On average 2.89 +/- 0.8 and 2.84 +/- 0.6 grafts/patient were completed in OP and CPB groups respectively. A majority (70%) of patients had either a triple or quadruple bypass. Coronary anastomoses were achieved with myocardial mechanical stabilization and heart "verticalization". Ischemic time was shorter in the OP group (29.8 +/- 0.9 vs 45 +/- 0.4 min, p < 0.05). Similarly, need for transfusion was significantly less (OP: 34 vs CPB: 66%, p < 0.005). Use of postoperative intra-aortic counterpulsation as well as the raise of CK-MB were lesser in the OP group. Operative mortality (OP: 1.6%, vs CPB: 2%, p = ns) and perioperative myocardial infarction rate (OP: 3.6% vs CPB: 4.2) were comparable for both groups. CONCLUSION: Off-pump complete coronary artery revascularization is an acceptable alternative to conventional surgery in a majority of patients with good results given progressive experience, rigorous technique, and adequate coronary artery stabilization.     

Inflamed fibronectin: an altered fibronectin enhances neutrophil adhesion

Recent investigations have emphasized the role of activated granulocytes in mediating vascular endothelial injury in the pathogenesis of shock lung. In vitro studies have indicated that tight adherence of the neutrophil to the endothelium is crucial for the development of cellular injury. Fibronectin is critical to cell-to- substratum and cell-to-cell interactions. Since fibronectin resides in plasma, on endothelial cell surfaces and is secreted into cell matrices, the adhesive properties of fibronectin must be modulated, lest universal cell agglomeration occur, yet be enhanced when cell attachment is appropriate. In these studies, treatment of fibronectin- coated surfaces with neutrophil release products increased the adhesion of activated neutrophils. Similarly, endothelial cells treated with neutrophil release products become a more adherent substrate for neutrophils. This enhanced adherence generated by treatment of fibronectin with neutrophil supernatants is inhibitable by heat and the lysosomal proteinase inhibitor, pepstatin-A. Neutrophil release products cause proteolytic fragmentation of fibronectin and enhanced fibronectin immunofluorescence on endothelial cells. In addition, neutrophils are more injurious to endothelial cells that have been pretreated with neutrophil release products. Neutrophils may enhance their own adherence to endothelial cells by altering fibronectin, and this altered, or "inflamed," fibronectin may serve as an amplifier of inflammation.     

18F-2-fluoro-2-deoxy-d-glucose positron emission tomography in staging of locally advanced breast cancer.

PURPOSE: To prospectively evaluate the effect of adding whole-body (18)F-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) to conventional screening for distant metastases in patients with locally advanced breast cancer (LABC). PATIENTS AND METHODS: All women with LABC referred for participation in the LABC Spinoza trial were considered eligible for this study. Patients were included if chest x-ray, bone scan, liver ultrasound, or computed tomography scan performed by the referring physician failed to reveal distant metastases. They underwent whole-body FDG PET scanning before therapy. Patients with subsequently proven distant metastases were switched to alternative forms of chemotherapy, hormonal therapy, or both. RESULTS: Among the 48 patients evaluated with PET, 14 had abnormal FDG uptake, and metastases were suspected in 12. After simple clinical evaluation (plain x-ray, history), 10 sites that were suggestive of abnormality remained. Further work-up revealed that four sites were metastases. Proven false positivity occurred in one patient with sarcoidosis. In the other five patients, the reason for abnormal FDG uptake (liver, lung, bone) remained unclear, and patients were treated as planned. Eleven months later, distant metastases were found in one patient at sites unrelated to the previous FDG uptake. CONCLUSION: The addition of FDG PET to the standard work-up of patients with LABC may lead to the detection of unexpected distant metastases. This may contribute to a more realistic stratification between patients with true stage III breast cancer and those who are in fact suffering from stage IV disease. Abnormal PET findings should be confirmed to prevent patients from being denied appropriate treatment.     

Hepatocyte growth factor and c-Met in cervical intraepithelial neoplasia: overexpression of proteins associated with oncogenic human papillomavirus and human immunodeficiency virus.

PURPOSE: High prevalence of squamous cervical intraepithelial neoplasia (CIN) linked to oncogenic human papillomavirus (HPV) exits in HIV-infected women. Hepatocyte growth factor (HGF) and its receptor, c-Met, promote cell proliferation and are involved in tumor progression. Nothing is yet known about their expression in low- and high-grade CIN. Therefore, the expression, localization, and behavior of HGF and c-Met in normal and dysplastic cervical epithelium were investigated. EXPERIMENTAL DESIGN: We studied normal cervical mucosa from 10 healthy women, and low- and high-grade cervical lesions, uninfected (condyloma acuminata) or infected with oncogenic HPVs, from 40 HIV-negative and 48 HIV-positive women, using in situ molecular techniques, immunocytochemistry and morphoquantitative methods. RESULTS: In 154 oncogenic HPV-infected CIN encountered in biopsy samples, the total number of epithelial cell layers increased significantly during lesion progression. This number was significantly higher in HIV-positive than in HIV-negative women for CIN1 and CIN2 (P < 0.025 to P < 0.01). In HIV-negative women, the number and percentage of HGF and c-Met immunostained cell layers, and the intensity of immunostaining were enhanced in oncogenic HPV-infected lesions as compared with normal mucosa and condyloma acuminata. The latter parameters were significantly higher in tissues of HIV-positive women (oncogenic HPV-infected CIN1 and CIN2, normal-appearing mucosa contiguous to CIN, condyloma acuminata) than in the corresponding tissues of HIV-negative women (P < 0.025 to P < 0.0001). CONCLUSIONS: Overexpression of HGF/c-Met complex strongly correlates with oncogenic HPV and HIV infection. This overexpressed complex may stimulate cell proliferation in condyloma acuminata and participate in tumor progression in oncogenic HPV-infected lesions.     

Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

Regionalization of perinatal care in Europe.

This review describes European health policies related to the place of birth of very preterm babies, and the organizational context in which these policies were enacted using data from two European studies. It also compiles available information on the place of birth of very preterm babies from the published literature. In Europe, there is significant diversity in approaches to the provision of intensive care services for the small proportion of pregnant women and babies that need it, both in terms of health policies and the supply and characteristics of maternity and neonatal units. These diverse models in countries with similar levels of development and medical technology could offer an opportunity to understand how different organizational characteristics affect access to care, health outcomes and resource use.     

Dihydropyrimidine dehydrogenase activity in normal, inflammatory and tumour tissues of colon and liver in humans

Background/Purpose: Dihydropyridmidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil (5FU). Although this catabolism is likely to occur in the liver in humans, there may be a local inactivation in tumours, modifying the efficacy of 5FU. The aim of this study was to examine the DPD activity in normal, inflammatory and malignant tissues from both the colon and the liver to assess the modifications of DPD activity in the process of tumourigenesis. Methods: DPD activity was evaluated in 107 patients, corresponding to 194 samples (70 colorectal tumour and normal colon, nine metastases secondary to a colon cancer, ten inflammatory colon, 20 samples of normal liver, seven from primary liver cancer, and eight from inflammatory liver). DPD activity was determined using an enzymatic reaction followed by analysis of 5FU and its catabolite dihydro-5FU by high-performance liquid chromatograph. Results were expressed as pmol of 5FU catabolized/min · mg protein. Results: DPD was highly variable in tumour and normal tissues, both from colon and liver. In colon, the correlation between DPD activity in tumour and normal mucosa was weak, even if it was statistically significant due to the higher number of samples. In inflammatory colon tissue (ulcerative colitis or Crohn's disease), DPD activity was significantly higher than in normal tissue (P=0.006). In liver metastases from colon cancer, DPD activity was not significantly different from that observed in primary colon tumour (P=0.32). In liver, DPD activity was significantly lower in primary liver tumour than in uninvolved liver specimens (P=0.001). In inflammatory liver tissue (hepatitis), DPD activity ranged between normal and tumour tissues, and did not differ significantly either from normal tissue or primary liver cancer. Conclusions: DPD activity was modified in colon and in liver during a pathological process and the dysregulation of DPD increased from a benign to a malignant tissue. Received: 22 November 1999 / Accepted: 25 January 2000     

菊叶三七生物碱成分的研究

从菊科蒂叶三七植物中分离出六个生物碱,对其中四个进行了鉴定。光谱数据证明:生物碱Ⅰ和Ⅱ分别为已知的千里光碱(senecionine,Ⅰ)和千里光菲灵碱(seneciphylline,Ⅱ),生物碱Ⅲ和Ⅳ为新成分,分别命名为菊三七碱甲(sineciphyllinine,Ⅲ)和菊三七碱乙[(E)-seneciphylline,Ⅳ]。     

Obstructive sleep apnea and the incidence and mortality of gastrointestinal cancers: a systematic review and meta-analysis of 5,120,837 participants

BackgroundEmerging evidence has shown higher overall cancer incidence in patients with obstructive sleep apnea. Gastrointestinal cancers, including esophageal, stomach, liver, pancreas, and colorectal cancers account for 26% of incident cancers. However, the link between gastrointestinal cancers and obstructive sleep apnea is still unclear. We performed a systematic review and meta-analysis (registered PROSPERO CRD42021220836) to investigate the association between obstructive sleep apnea and incidence of gastrointestinal cancer.MethodsWe searched four electronic databases (PubMed, Embase, Cochrane Library, Scopus) and included studies published from inception till 15th November 2020 reporting the association of obstructive sleep apnea with gastrointestinal cancer incidence. Extracted data was meta-analyzed in a random-effects model.ResultsA total of seven studies were included, forming a combined cohort of 5,120,837 patients. Studies which adjusted for demographics and comorbidities were included in meta-analysis. Among four studies with 7–11 years of median follow-up, patients with obstructive sleep apnea experienced increased incidence of colorectal cancer (HR 1.70, 95% CI: 1.48–1.96, I²=22%). Pancreatic cancer incidence was nominally increased in three studies (HR 1.36, 95% CI: 0.88–2.09, I²=96), though this was not statistically significant. There was no association between obstructive sleep apnea and liver cancer incidence among three studies (HR 0.99, 95% CI: 0.81–1.22, I²=84). However, the lack of a statistically significant relationship between obstructive sleep apnea and pancreatic cancer in our meta-analysis does not necessarily imply the true absence of an association.ConclusionsAn increased risk of colorectal cancer was seen in patients with obstructive sleep apnea among studies with long-term follow-up. Further research is required to explore the utility of incorporating obstructive sleep apnea screening into colorectal cancer screening guidelines to identify high-risk individuals and to confirm a possible association of obstructive sleep apnea with pancreatic cancer.PROSPERO RegistrationCRD42021220836