AUGER INJURIES IN THE WIMMERA REGION 1987–95

Background: Eighteen cases of auger injuries in the Wimmera region of Victoria were treated over 8 years. Methods: The records of auger related injuries presenting to Wimmera Base Hospital from March 1987 to March 1995 were reviewed. Results: Five of these were severe injuries. Sixteen were male farmers. Their fingers were most commonly injured by being caught in the auger flight. Conclusions: Augers have numerous mechanical features which make them one of the most potentially dangerous pieces of farm equipment. This, combined with human error and fatigue, results in significant but preventable morbidity in a hardworking population.     

An Unexpected Counter‐Regulatory Role of IL‐10 in B‐Lymphocyte‐Mediated Transplantation Tolerance

Monoclonal antibody against the CD45RB protein induces stable transplantation tolerance to multiple types of allograft. We have previously established that this tolerance protocol relies on the regulatory function of B lymphocytes for its effect. B lymphocytes have also been reported to participate in immune regulation in several other settings. In most of these systems, the regulatory function of B lymphocytes depends on the production of IL‐10. Therefore, we investigated the role of IL‐10 in the anti‐CD45RB model of B‐cell‐mediated transplantation tolerance. Surprisingly, using antibody‐mediated neutralization of IL‐10, IL‐10‐deficient recipients and adoptive transfer of IL‐10‐deficient B lymphocytes, we found that IL‐10 actually counter‐regulates tolerance induced by anti‐CD45RB. Furthermore, neutralization of IL‐10 reduced the development of chronic allograft vasculopathy compared to anti‐CD45RB alone and reduced the production of graft reactive alloantibodies. These data suggest that the participation of regulatory B lymphocytes in transplantation tolerance may be distinct from how they operate in other systems. Identifying the specific B lymphocytes that mediate transplantation tolerance and defining their mechanism of action may yield new insights into the complex cellular network through which antigen‐specific tolerance is established and maintained.     

CARDIAC FUNCTION IN ANEURYSMAL SUBARACHNOID HAEMORRHAGE: A STUDY OF ELECTROCARDIOGRAPHIC AND ECHOCARDIOGRAPHIC ABNORMALITIES

Electrocardiographic (ECG) changes are reported frequently aftersubarachnoid haemorrhage (SAH). The aim of this study was toinvestigate the functional significance of ECG changes by echocardiographicassessment of cardiac function. Forty-five patients with intracranialaneurysms were studied. All patients had a 12-lead ECG and atwo-dimensional echocardiogram. After patients with an historyof chronic cardiac disease (n = 4) were excluded, only fourpatients were found to have wall motion abnormalities. Thesepatients had only minor ECG abnormalities, but severe neurologicaldysfunction. Conversely, patients with other ECG abnormalitiesincluding the deep inverted T waves associated usually withSAH, had normal echocardiograms. We conclude that the ECG isnot an accurate predictor of myocardial function after SAH andthat myocardial dysfunction is related more closely to severityof neurological condition.     

EFFECTS OF DIFFERENT PERIODS OF GASTRIC ISCHAEMIA IN THE VIABILITY OF THE TISSUE OF BODY,FUNDUS AND ANTRUM REGION OF RABBIT STOMACH

BACKGROUND:

Despite the rich vascular arcade of the stomach, gastric ischemia represents an important medical challenge and can be the consequence of obstructive or non-obstructive vascular processes of pathological or iatrogenic origin.

AIM:

To assess the effects of acute gastric ischaemia on the different regions of the stomach.

METHOD:

Fifteen New Zeland rabbits were divided into three groups: group 1, animals were observed during 3 h; group 2, during 6 h; group 3, during 12 h. Rabbit stomachs were subjected to devascularization of the greater and lesser curvatures. After predetermined time, the stomachs were removed for macro and microscopic studies.

RESULTS:

Haemorrhagic necrosis was more marked in the gastric fundus and body. In contrast, the antropylorus remained preserved in 80% of the animals. Necrosis of the gastric body and fundus mucosa were observed in all animals after 6 h and 12 h of ischaemia.

CONCLUSION:

Acute gastric ischaemia in rabbits produces haemorrhagic necrosis of the gastric fundus and body even in a short period of time. Beside this, the antropyloric region was significantly more resistant to ischaemia.     

P53 TUMOUR SUPPRESSOR GENE EXPRESSION IN HYPERPARATHYROIDISM

Background: Mutations of the p53 tumour suppressor gene lead to the loss of control of normal cellular proliferation and differentiation and have been shown to be associated with the development of malignancy. Method: Archival paraffin resection specimens from 86 cases of hyperparathyroidism treated surgically using the rabbit poly-clonal CM1 antibody were investigated to detect p53 immunoreactivity in these sections. Results: Eighteen of the 86 sections examined (21%) showed nuclear immunoreactivity. No correlation was detected between tumour histology and p53 immunoreactivity (P = 0.45). nor was there any correlation between tumour clonality and immunoreactivity (P = 0.54). Multiple endocrine neoplasia type I (MEN 1) status did not correlate with p53 immunoreactivity. A significant correlation between p53 immunoreactivity and preparathyroidectomy calcium levels of > 1.5 mmol/L was detected (P < 0.005) although no correlation was noted between p53 immunoreactivity and higher levels of preparathyroidectomy intact parathyroid hormone (PTH) levels. Conclusion: A relationship is postulated between abnormal serum calcium regulation and p53 mutation in hypercalcaemic states associated with hyperparathyroidism.     

胆管癌的基因表达及其临床意义

目的 寻找对胆管癌早期诊断和判断其预后有意义的指标。方法 复习国内外文献有关胆管癌组织中各种基因的改变及其临床意义。结果 胆管癌组织中存在多种基因的点突变、缺失和过度表达,其中以Ｋ－ｒａｓ基因的研究最为深入。结论 Ｋ－ｒａｓ基因点突变的检测将有助胆管癌的早期发现和判断其预后。     

肝细胞癌中SLIT2基因甲基化状态研究

目的 SLIT2基因甲基化已在多种肿瘤中被发现,我们拟了解肝细胞癌(HCC)中SLIT2基因的甲基化状态及临床意义。方法采用甲基化特异性聚合酶链反应(MSP)技术,检测50例HCC癌组织及相应的癌旁组织,4个HCC细胞系, 8例肝血管瘤旁和4例供肝组织,了解SLIT2基因在上述组织中的甲基化状态,并分析其与临床资料间的相关性。结果 8例肝血管瘤旁和4例供肝组织均未发生甲基化,4个HCC细胞系有3个出现甲基化。50例HCC癌组织及其相应的癌旁组织中, 分别检测到39例(78％)和26例(52％)发生甲基化;癌组织与癌旁组织甲基化率比较,有显著统计学差异(P=0．006);TNM Ⅲ期组SLIT2甲基化率高于TNM Ⅰ／Ⅱ期组(P=0．035);甲基化阳性组的半年无瘤生存率低于阴性组,但差异无统计学意义 (P=0．208)。结论 SLIT2基因甲基化是HCC中的频发事件,可能参与HCC的发展。     

Laparoscopic sphincter‐preserving total mesorectal excision: 10‐year report

Aim Total mesorectal excision (TME) is currently the gold standard for resection of mid or low rectal cancer and is associated with a low local recurrence rate. However, few studies have reported the long‐term oncological outcome following use of a laparoscopic approach. The aim of this study was to evaluate the long‐term oncological outcome after laparoscopic sphincter‐preserving TME with a median follow up of about 4 years. Method Patients with mid or low rectal cancer who underwent laparoscopic sphincter‐preserving TME with curative intent between March 1999 and March 2009 were prospectively recruited for analysis. Results During the 10‐year study period, 177 patients underwent laparoscopic sphincter‐preserving TME with curative intent for rectal cancer. Conversion was required in two (1%) patients. There was no operative mortality. At a median follow‐up period of 49 months, local recurrence had occurred in nine (5.1%) patients. The overall metastatic recurrence rate after curative resection was 22%. The overall 5‐year survival and 5‐year disease‐free survival in the present study were 74% and 71%, respectively. Conclusion The results of this study show that laparoscopic sphincter‐preserving TME is safe with long‐term oncological outcomes comparable to those of open surgery.     

Adenovirus‐mediated viral IL‐10 gene transfer prolongs survival of xenogeneic spheroidal aggregate‐cultured hepatocytes

Abstract Xenotransplantation of hepatocytes appears to be a novel promising therapy for some forms of liver disease, and may well overcome the problem of donor shortage. We have previously reported that hepatocytes with a spheroidal shape (spheroids) are ideal for cell transplantation. The application of gene transfer techniques to this hepatocyte transplantation could possibly regulate the xenogeneic rejection reaction and, therefore, result in prolongation of the survival of the transplanted hepatocytes. In this study, we chose the adenovirus as a vector and an immunosuppressive cytokine named viral IL‐10 (vIL‐10) for transfection. A series of experiments was performed to elucidate the efficacy of transfection to the spheroids with adenovirus vectors and the effect of transfected vIL‐10 on the survival of xenogeneic hepatocytes. We examined the cell survival quantitatively by evaluating β‐galactosidase (β‐gal) activity, which was transfected into the hepatocytes in the xenogeneic spleen, and semi‐quantitatively by the histological findings. The results of in‐vitro studies identified an efficient expression of the β‐gal gene within the spheroids infected with Ad‐CMVLacZ (LacZ‐encoding adenovirus vector with CMV promotor) and the presence of BCRF1 mRNA within the spheroids transfected with AdCMVvIL‐10 (vIL‐10‐expressing adenovirus vector with CMV promotor) under the condition of 1 MOI, for 1 h. Xenogeneic hepatocytes with a spheroidal shape showed comparable survival to syngeneic hepatocytes for up to 4 days after transplantation with co‐transplantation of the vIL‐10‐transfected hepatocytes. From this study, we concluded that adenovirus‐mediated vIL‐10 gene transfer prolongs the survival of xenogeneic hepatocyte spheroids. Furthermore, spheroids possess ideal properties for gene transfection, as well as cell transplantation.     

多药耐药基因MDR1在原发性肝癌组织中表达的意义

肿瘤细胞对化疗药物产生抗药性的原因有几种，其中最主要的是多药耐药基因MDR1。应用免疫组化方法测定30例原发性肝癌（PHC）癌组织和癌周组织中MDR1的表达产物Pgp（P-gly-coprotein，PgP），结果显示，PHC癌组织中MDR1基因表达阳性率（60．0％）远较癌周组织高（23．3％）。化疗后肿瘤组织MDR1阳性率（88．9％）较未化疗瘤的癌组织（47．6％）高。结合临床资料分析，MDR1基因的过度表达在我国PHC的内在性和获得性药物耐受产生中起着一定的作用。关键词:##4多药耐药基因;;原发性肝癌     

Lentivirus IL‐10 Gene Therapy Down‐Regulates IL‐17 and Attenuates Mouse Orthotopic Lung Allograft Rejection

The purpose of the study was to examine the effect of lentivirus‐mediated IL‐10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL‐10 may regulate posttransplant immunity mediated by IL‐17. Lentivirus‐mediated trans‐airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor‐mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC‐mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor‐mismatched allografts, IL‐10‐encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus‐luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL‐10 gene therapy also significantly reduced gene expression of IL‐17, IL‐23, and retinoic acid‐related orphan receptor (ROR)‐γt without affecting levels of IL‐12 and interferon‐γ (IFN‐γ). Cells expressing IL‐17 were dramatically reduced in the allograft lung. In conclusion, lentivirus‐mediated IL‐10 gene therapy significantly reduced expression of IL‐17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation.     

Hyaluronan Up‐Regulates IL‐10 Expression in Fibroblast‐Like Synoviocytes from Patients with Tibia Plateau Fracture

Progression to osteoarthritis (OA) is a frequent sequela of severe articular fracture, particularly when weight‐bearing joints are involved. Prevention from post‐traumatic OA remains a challenge. Hyaluronan (HA) therapy is reported to represent a safe and effective treatment for patients with OA and rheumatoid arthritis. However, the capacity of HA to prevent the occurrence of osteoarthritic changes in fractured joints has not been demonstrated. The present study was undertaken to examine the effects of HA on expression of six OA‐related proteins in fibroblast‐like synoviocytes (FLS) from 10 patients with tibia plateau fracture. OA‐related factors were quantified using a sandwich enzyme‐linked immunosorbent assay. Regardless of induction of the FLS with interleukin (IL)‐1β, HA was found to down‐regulate expression of catabolic factors (IL‐1β, matrix metalloproteinase‐3, and tumor necrosis factor‐α) and to up‐regulate production of anti‐catabolic factors (tissue inhibitors of metalloproteinase‐1 and metalloproteinase‐2). HA also enhanced expression of IL‐10, an anti‐inflammatory cytokine, in FLS. Our results indicated that HA can promote the expression of both antiinflammatory and structure‐protective factors in FLS of patients with tibia plateau fracture. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:495–500, 2011     

SURGERY IN THE CONFLICT REGION OF SRI LANKA

Background: Médecins Sans Frontières provides medical support to Batticaloa, a town on the east coast, which is in the conflict region of Sri Lanka. Methods: Information on the range of pathology, the services provided and the diseases treated was collected from a 25 day assignment in mid-1995. Results: Services and facilities are limited and the amount of work is extensive, as indicated by the 248 patients who had one or more operations and 814 surgical cases who were admitted. Ten per cent of the work was with conflict-injured patients and the remainder covered a wide range of specialties. Complications were surprisingly few. Conclusions: The surgical support supplied through MCdecins Sans Frontitres gives the people of Batticaloa much needed medical care and allows surgeons the opportunity to have an enormously satisfying experience.