Complex Fistulae in Crohn's Disease

Journal of the American College of Surgeons. Jan, 2002  |  Pubmed ID: 11800345

An Evaluation of the Prognostic Significance of Vascular Endothelial Growth Factor in Node Positive Primary Breast Carcinoma

International Journal of Oncology. Apr, 2002  |  Pubmed ID: 11894115

Angiogenesis is intimately related to the growth and progression of tumours and must be induced to facilitate growth beyond a minimum size. It has been implicated in the development of metastases and survival in breast carcinoma. VEGF is a cytokine that plays an important role in angiogenesis. Its expression is increased in solid tumours during induction of angiogenesis and it has been implicated as a prognostic marker in patients with node negative breast carcinoma. We studied VEGF expression, in a series of patients with node positive breast carcinoma and examined histopathological parameters of the tumour and the prognostic value of VEGF expression. Specimens from 108 cases of node positive breast cancer were stained for VEGF using an antibody suitable for use on formalin fixed tissue. VEGF staining was cytoplasmic and was scored by intensity and the percent positive cells. Patients with positive VEGF staining (n=48) were compared with patients with negative VEGF staining (n=60). Demographic criteria were similar in both groups. Only one (12%) patient with lobular carcinoma and one (14%) patient with medullary carcinoma expressed VEGF compared with 46 (49%) patients with ductal carcinoma (NOS). DCIS was present in 60 tumours. There was a strong correlation between staining in DCIS and the adjacent invasive tumours. There was no significant association between VEGF staining and T stage, tumour size or the number of positive lymph nodes. VEGF expression had no prognostic significance either for disease-free or overall survival in patients with node positive disease. This study failed to support a role for VEGF as a prognostic marker in patients with node positive breast carcinoma.

Traumatic Transection of the Pancreas

American Journal of Surgery. Feb, 2002  |  Pubmed ID: 11918886

Primary Amyloidosis of the Stomach: EUS Appearances

Gastrointestinal Endoscopy. Aug, 2002  |  Pubmed ID: 12145619

The Acute Phase Response in Breast Carcinoma

Anticancer Research. Mar-Apr, 2002  |  Pubmed ID: 12168939

The acute phase response follows tissue injury, trauma or infection and maintains homeostasis. It may also be activated in patients with malignancy and studies have suggested that it is associated with a poor prognosis. This study examined C-reactive protein (CRP) and serum amyloid A (SAA) in patients with breast carcinoma, both at presentation and during follow-up, to assess the value of the acute phase proteins in patient management.

Leiomyoma of the Esophagus

American Journal of Surgery. Aug, 2002  |  Pubmed ID: 12169363

Intraperitoneal Pethidine Versus Intramuscular Pethidine for the Relief of Pain After Laparoscopic Cholecystectomy: Randomized Trial

World Journal of Surgery. Dec, 2002  |  Pubmed ID: 12360380

Laparoscopic cholecystectomy is widely used and may be performed as an ambulatory procedure. We undertook a randomized comparison of the benefits of intraperitoneal pethidine compared with intramuscular pethidine for postoperative analgesia following laparoscopic cholecystectomy. A series of 100 consecutive American Society of Anesthesiologists (ASA) I or II patients were randomly assigned to intramuscular pethidine (54 patients) or intraperitoneal pethidine (46 patients). Each was combined with intraperitoneal bupivacaine. The primary endpoints were the pain and nausea scores at intervals after operation. All recruited patients completed the study. Pain scores at rest and upon movement were significantly lower in the group receiving the intraperitoneal pethidine at each of the time periods examined (pain at rest at 4 hours: 1.6 +/- 0.8 vs. 2.4 +/- 0.9 cm; p < 0.001; pain upon movement at 4 hours: 2.1 +/- 0.9 vs. 3.1 +/- 1.2 cm; p < 0.001). The total dose of pethidine administered via patient-controlled analgesia (PCA) during the first 24 hours after surgery was also significantly lower in this group (total dose 50.9 +/- 3.9 vs. 55.9 +/- 4.4 mg; p < 0.001). There were no significant differences in the respiratory rate at any of the time periods. Intraperitoneal pethidine analgesia was superior to an equivalent dose of intramuscular pethidine for the relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. This was achieved at the expense of increased nausea but no significant increase in vomiting. The accessibility of this route of analgesia administration has implications for patients undergoing laparoscopic procedures, particularly with the recent trend toward increased use of ambulatory techniques.

Venous Thrombosis

American Journal of Surgery. Aug, 2003  |  Pubmed ID: 12885612

Cystic Duct Remnant and the 'post-cholecystectomy Syndrome'

Hepato-gastroenterology. Jan-Feb, 2004  |  Pubmed ID: 15011827

Post-cholecystectomy syndrome refers to a wide spectrum of conditions that pose a challenging diagnostic dilemma. Cystic duct remnant, defined as a residual duct greater than 1 cm in length, may, in the presence of stones, cause post-cholecystectomy syndrome. In this report, 4 patients with post-cholecystectomy syndrome due to cystic duct remnant are described. All underwent laparoscopic cholecystectomy and one was converted to open. The patients presented with pain 10 months to 9 years post-cholecystectomy and investigations demonstrated cystic duct remnant. All patients underwent successful resection with resolution of symptoms. In this era of laparoscopic surgery, where surgery favors a long cystic duct remnant, we should be aware of cystic duct stones as a possible cause of postcholecystectomy syndrome. This report highlights magnetic resonance cholangiopancreatography as the optimal method for evaluating the biliary tract in these cases.

Long-term Quality of Life Following Pancreaticoduodenectomy

Hepato-gastroenterology. May-Jun, 2005  |  Pubmed ID: 15966234

This study examined long-term quality of life in an unselected consecutive cohort of patients undergoing pancreaticoduodenectomy, both Whipple and total, for benign and malignant disease.

Anti-metastatic Effects of Viral and Non-viral Mediated Nk4 Delivery to Tumours

Genetic Vaccines and Therapy. 2009  |  Pubmed ID: 19272140

The most common cause of death of cancer sufferers is through the occurrence of metastases. The metastatic behaviour of tumour cells is regulated by extracellular growth factors such as hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, and aberrant expression/activation of the c-Met receptor is closely associated with metastatic progression. Nk4 (also known as Interleukin (IL)32b) is a competitive antagonist of the HGF c-Met system and inhibits c-Met signalling and tumour metastasis. Nk4 has an additional anti-angiogenic activity independent of its HGF-antagonist function. Angiogenesis-inhibitory as well as cancer-specific apoptosis inducing effects make the Nk4 sequence an attractive candidate for gene therapy of cancer. This study investigates the inhibition of tumour metastasis by gene therapy mediated production of Nk4 by the primary tumour. Optimal delivery of anti-cancer genes is vital in order to achieve the highest therapeutic responses. Non-viral plasmid delivery methods have the advantage of safety and ease of production, providing immediate transgene expression, albeit short-lived in most tumours. Sustained presence of anti-angiogenic molecules is preferable with anti-angiogenic therapies, and the long-term expression mediated by Adeno-associated Virus (AAV) might represent a more appropriate delivery in this respect. However, the incubation time required by AAV vectors to reach appropriate gene expression levels hampers efficacy in many fast-growing murine tumour models. Here, we describe murine trials assessing the effects of Nk4 on the spontaneously metastatic Lewis Lung Carcinoma (LLC) model when delivered to primary tumour via plasmid lipofection or AAV2 vector. Intratumoural AAV-Nk4 administration produced the highest therapeutic response with significant reduction in both primary tumour growth and incidence of lung metastases. Plasmid-mediated therapy also significantly reduced metastatic growth, but with moderate reduction in primary subcutaneous tumour growth. Overall, this study demonstrates the potential for Nk4 gene therapy of metastatic tumours, when delivered by AAV or non-viral methods.

Antegrade Deligation of Iatrogenic Distal Ureteric Obstruction Utilising a High Pressure Balloon Dilatation Technique

Gynecologic Oncology. Sep, 2009  |  Pubmed ID: 19481789

Iatrogenic trauma is the leading cause of ureteric injury with an incidence in abdominal and pelvic surgery varying between 0.4 and 2.5%.

Little Old Ladies' Hernia: a Clinical Diagnostic Conundrum

BMJ Case Reports. 2009  |  Pubmed ID: 21691397

Rapid Resolution of Phlegmonous Gastritis Using Antibiotics Alone

BMJ Case Reports. 2009  |  Pubmed ID: 21789106

The Wandering Splenunculus: a Diagnostic Dilemma

BMJ Case Reports. 2009  |  Pubmed ID: 21829427

Bacteria As Vectors for Gene Therapy of Cancer

Bioengineered Bugs. Nov-Dec, 2010  |  Pubmed ID: 21468205

Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. Gene or cell therapies have emerged as realistic prospects for the treatment of cancer, and involve the delivery of genetic information to a tumor to facilitate the production of therapeutic proteins. However, there is still much to be done before an efficient and safe gene medicine is achieved, primarily developing the means of targeting genes to tumors safely and efficiently. An emerging family of vectors involves bacteria of various genera. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally. Furthermore, invasive species can deliver heterologous genes intra-cellularly for tumor cell expression. Here, we review the use of bacteria as vehicles for gene therapy of cancer, detailing the mechanisms of action and successes at preclinical and clinical levels.

Mycobacterium Avium Subsp. Paratuberculosis (MAP) As a Modifying Factor in Crohn's Disease

Inflammatory Bowel Diseases. Feb, 2010  |  Pubmed ID: 19824071

Crohn's disease (CD) is a multifactorial syndrome with genetic and environmental contributions. Mycobacterium avium subspecies paratuberculosis (MAP) has been frequently isolated from mucosal tissues of patients with CD but the cellular immune response to this bacterium has been poorly described. Our aim was to examine the influence of MAP on T-cell proliferation and cytokine responses in patients with inflammatory bowel disease (IBD).

Cervicovaginal Fluid and Semen Block the Microbicidal Activity of Hydrogen Peroxide Produced by Vaginal Lactobacilli

BMC Infectious Diseases. 2010  |  Pubmed ID: 20482854

H2O2 produced by vaginal lactobacilli is believed to protect against infection, and H2O2-producing lactobacilli inactivate pathogens in vitro in protein-free salt solution. However, cervicovaginal fluid (CVF) and semen have significant H2O2-blocking activity.

AAV2-mediated in Vivo Immune Gene Therapy of Solid Tumours

Genetic Vaccines and Therapy. 2010  |  Pubmed ID: 21172020

Many strategies have been adopted to unleash the potential of gene therapy for cancer, involving a wide range of therapeutic genes delivered by various methods. Immune therapy has become one of the major strategies adopted for cancer gene therapy and seeks to stimulate the immune system to target tumour antigens. In this study, the feasibility of AAV2 mediated immunotherapy of growing tumours was examined, in isolation and combined with anti-angiogenic therapy.

Preclinical Evaluation of Gene Delivery Methods for the Treatment of Loco-regional Disease in Breast Cancer

Experimental Biology and Medicine (Maywood, N.J.). Apr, 2011  |  Pubmed ID: 21444371

Preclinical results with various gene therapy strategies indicate significant potential for new cancer treatments. However, many therapeutics fail at clinical trial, often due to differences in tissue physiology between animal models and humans, and tumor phenotype variation. Clinical data relevant to treatment strategies may be generated prior to clinical trial through experimentation using intact patient tissue ex vivo. We developed a novel tumor slice model culture system that is universally applicable to gene delivery methods, using a realtime luminescence detection method to assess gene delivery. Methods investigated include viruses (adenovirus [Ad] and adeno-associated virus), lipofection, ultrasound (US), electroporation and naked DNA. Viability and tumor populations within the slices were well maintained for seven days, and gene delivery was qualitatively and quantitatively examinable for all vectors. Ad was the most efficient gene delivery vector with transduction efficiency >50%. US proved the optimal non-viral gene delivery method in human tumor slices. The nature of the ex vivo culture system permitted examination of specific elements. Parameters shown to diminish Ad gene delivery included blood, regions of low viability and secondary disease. US gene delivery was significantly reduced by blood and skin, while tissue hyperthermia improved gene delivery. US achieved improved efficacy for secondary disease. The ex vivo model was also suitable for examination of tissue-specific effects on vector expression, with Ad expression mediated by the CXCR4 promoter shown to provide a tumor selective advantage over the ubiquitously active cytomegalovirus promoter. In conclusion, this is the first study incorporating patient tissue models in comparing gene delivery from various vectors, providing knowledge on cell-type specificity and examining the crucial biological factors determining successful gene delivery. The results highlight the importance of in-depth preclinical assessment of novel therapeutics and may serve as a platform for further testing of current, novel gene delivery approaches.

Targeting of Breast Metastases Using a Viral Gene Vector with Tumour-selective Transcription

Anticancer Research. May, 2011  |  Pubmed ID: 21617219

Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression.

In Vaginal Fluid, Bacteria Associated with Bacterial Vaginosis Can Be Suppressed with Lactic Acid but Not Hydrogen Peroxide

BMC Infectious Diseases. 2011  |  Pubmed ID: 21771337

Hydrogen peroxide (H2O2) produced by vaginal lactobacilli is generally believed to protect against bacteria associated with bacterial vaginosis (BV), and strains of lactobacilli that can produce H2O2 are being developed as vaginal probiotics. However, evidence that led to this belief was based in part on non-physiological conditions, antioxidant-free aerobic conditions selected to maximize both production and microbicidal activity of H2O2. Here we used conditions more like those in vivo to compare the effects of physiologically plausible concentrations of H2O2 and lactic acid on a broad range of BV-associated bacteria and vaginal lactobacilli.