Laparoscopic Roux-en-Y Gastric Bypass with 2-metre Long Biliopancreatic Limb for Morbid Obesity: Technique and Experience with the First 150 Patients

Background: Laparoscopic Roux-en-Y gastric bypass (RYGBP) is being performed widely as a treatment of choice for morbid obesity. We present our method and experience with the first 150 consecutive cases of laparoscopic RYGBP with a 2-m long biliopancreatic limb (BP-limb). Methods: Between November 2001 and November 2003, a prospective analysis of 150 patients was performed identifying technical success and complications. Before surgery, patients underwent a strict multidisciplinary behavioral program. At operation the stomach was transected proximally with a linear stapler (60-mm, Endo-GIA) to create a prolongation of the esophagus (gastric tube) along the lesser curvature, resulting in a 40-50 ml pouch. Two meters of the proximal jejunum were bypassed (BP-limb), creating an antecolic Roux-en-Y gastro-jejunostomy to the posterior wall of the gastric tube using a 45-mm linear Endo-GIA stapler. The entero-anastomosis was created 50 cm below the gastro-jejunostomy, also with a 45-mm linear Endo-GIA. Results: Mean BMI was 50.0, and 78% of patients were females. With 100% follow-up, we found an EWL of 50% 6 months after surgery, gradually rising to 80% after 18 months. The mean operating time was 116 min for the first 50 cases and decreased to 82 min for the last 50 cases. Intestinal leakage occurred in 5 patients (3%) and bleeding in 5 (3%). Most of these complications occurred in the first 50 cases, and all but one were treated successfully with an early laparoscopic re-operation. Marginal ulcers were found in 16.6% of patients. No internal hernias have occurred. Conclusion: The operation demands advanced laparoscopic skills, but technically it is relatively simple and has an acceptable complication rate. Short-term results regarding excess weight loss are at least comparable to the RYGBP with a long alimentary limb.     

An ‘early warning system’ for health needs: surveillance of the quality of clinical services by audit of extra-contractual referrals (ECRs)

Extra-contractual referrals (ECRs) can be a cause of considerable anxiety to purchasing authorities, mainly because of their potential to generate unexpected expenditure. But ECRs can also be used as a tool for monitoring the demand for, and quality of, clinical services. ECRs were studied in the Darlington Health Authority district using a variety of methods including inter-disciplinary meetings, a series of interviews with local GPs, and a questionnaire to general practitioners on 230 consecutive ECRs. The methods and results of the questionnaire study are presented. The commonest reasons for making ECRs included the mistaken belief that a contract existed with the ECR provider, patient dissatisfaction with the local provider, and referral to benefit from shorter waiting lists. ECRs for bone-mass densitometry, orthopaedics, and ear nose and throat services were over-represented. Questionnaire results were validated by comparison with an interview study of all GPs in the district. We conclude that trends in ECRs can be monitored as a convenient ‘early warning system’ to alert purchasing authorities to changes in demand or perceived problems with local provider units. ECR data must be interpreted in the context of further local background information from sources such as GPs and public health physicians. In the case of Darlington, scrutiny of ECRs has led to changes in services and contracts.     

Natural kinds, natural history and the clinician-researcher

Recent medical research has been based on a flawed rationale of clinical innovation (here termed the 'basic-to-mega model') which neglects the human organism as a vital focus of clinical scientific study. The consequent over-concentration upon cellular and population levels of analysis has probably damaged the rate of therapeutic progress. The key role in medical research should be acknowledged to lie with clinician-researchers whose 'experimental animal' is the patient and whose 'end-points' are health and disease. The distinctive strength of the clinician-researcher derives from an ability to combine understanding of the 'natural kinds' (i.e. true biological categories) relevant to human disease, with experience of the 'natural history' of disease (i.e. its longitudinal pattern, including the response to interventions). Such knowledge is explicitly formalized by the activities of clinical science and clinical epidemiology. A sufficient supply of active clinician-researchers is the catalyst of innovation, and an insufficient supply is currently a rate-limiting factor in therapeutic progress.      

Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States

In industrialized populations, Hodgkin's disease (HD) has an initial peak in young adulthood, whereas in economically developing populations the initial peak occurs in childhood. This pattern resembles that of infection with poliovirus and suggests an infectious cofactor in the etiology. Serologic studies have linked Epstein-Barr virus (EBV) to young adult and adult HD, and viral nucleic acids and antigens have been detected in a subset of Hodgkin's tumor specimens. To investigate the association of childhood HD with EBV we studied tumor specimens from 11 children treated in Honduras and 25 children treated in the United States using in situ hybridization and antigen detection techniques. Among the patients from Honduras, tumor specimens from all cases were EBV positive. Among the patients from the United States, tumor specimens from six of seven patients with mixed cellularity histology, 2 of 15 with nodular sclerosis histology, and neither of two patients with lymphocyte-predominant histologies were EBV positive. These findings support the hypothesis that EBV contributes to the pathogenesis of HD in children, particularly in mixed cellularity HD, and raises the possibility that there are important geographic, racial, or ethnic factors in the EBV association with HD.     

许旺细胞增殖和分化过程中的信号通路

目的:探讨许旺细胞增殖和分化过程中细胞内各种信号通路及其关联性。资料来源:应用计算机检索Medline 1994-01/2006-12和Embase 1994-01/2006-12期间的有关许旺细胞增殖和分化相关的信号通路的文献,检索词“Schwann cell;proliferation;differentiation;signal transduction”,并限定文章语言种类为英文。资料选择:选取与许旺细胞增殖和分化相关的有关信号通路的文献,进行初审,删除与信号通路不相关的研究,然后查找余下的文献全文。质量评价主要考察资料的真实性,调查设计是否严密,实施过程是否严格,统计学处理是否合理。资料提炼:共检索54篇与许旺细胞增殖和分化相关的有关信号通路的文献研究,纳入30篇文章。14篇有关许旺细胞增殖,12篇许旺细胞分化,4篇是其他的相关信号通路。资料综合:许旺细胞的分化和基因表达是通过各种细胞外信号来调控的,多种信号通路相互联系。来自于受体酪氨酸激酶,丝裂原活化蛋白激酶,磷酯酰肌醇-3激酶通路的信号在许旺细胞增殖和分化过程中都有很重要的作用,它们之间的平衡决定了细胞最后的功能。而细胞内膜受体G蛋白偶联的环磷腺苷浓度促进了细胞的各种功能,也参与调节了其他信号通路。结论:许旺细胞增殖和分化过程是多种信号通路相互联系完成的,阐明不同信号通路之间的关系以及它们的交互作用对于揭示许旺细胞的生物学功能有重要的意义。     

Pathology and biofilm formation in a porcine model of staphylococcal osteomyelitis

A porcine model was used to examine the potential of human and porcine Staphylococcus aureus isolates to induce haematogenously spread osteomyelitis. Pigs were inoculated in the right femoral artery with one of the following S. aureus strains: S54F9 (from a porcine lung abscess; n = 3 animals), NCTC-8325-4 (a laboratory strain of human origin; n = 3 animals) and UAMS-1 (a human osteomyelitis isolate; n = 3 animals). Two pigs were sham inoculated with saline. At 11 or 15 days post infection the animals were scanned by computed tomography before being killed and subjected to necropsy examination. Osteomyelitis lesions were present in the right hind limb of all pigs inoculated with strain S54F9 and in one pig inoculated with strain NCTC-8325-4. Microscopically, there was extensive loss of bone tissue with surrounding granulation tissue. Sequestrated bone trabeculae were intermingled with colonies of S. aureus as demonstrated immunohistochemically. By peptide nucleic acid fluorescence in situ hybridization bacterial aggregates were demonstrated to be embedded in an opaque matrix, indicating that the bacteria had formed a biofilm. Development of experimental osteomyelitis was therefore dependent on the strain of bacteria inoculated and on the formation of a biofilm.     

Expression of matrix metalloproteinase-9 and -12 in porcine lung infections

Matrix metalloproteinases (MMPs) play a variety of roles during organogenesis, in the immune response and during acute and chronic diseases as well as in tissue remodelling. During the last decade, the pig has become used increasingly as a model for human diseases; however, studies on the expression of porcine MMPs are limited. In the present study species-specific antibodies were produced to investigate the expression of MMP-9 and MMP-12 immunohistochemically in lungs from pigs infected with Actinobacillus pleuropneumoniae, Pasteurella multocida and Staphylococcus aureus. The immunolabelling of lung tissues (one infected and one control pig representing each infection) was evaluated for cellular distribution and intensity, which was scored semiquantitatively. When compared with healthy, non-infected controls, the expression of both MMP-9 and MMP-12 was higher in infected lungs. The highest expressions were seen in the alveolar epithelium (MMP-9) and alveolar macrophages (MMP-12). These results are in accordance with studies of human lungs.