Biomedical subjects
Publications and source records attributed to D Evoy.
We report the first case of bilateral temporomandibular joint (TMJ) dislocation in a woman after endoscopy. We go on to discuss the case reports published in the literature, with particular focus on potential factors that may predispose to this complication, and we offer some suggestions on dealing with this significant complication.
OBJECTIVES: endovascular repair of abdominal aortic aneurysms (E-AAA) has in recent years developed as an alternative to the conventional open repair (C-AAA). Adverse outcomes following the open approach may relate to immune cell activation and the systemic inflammatory response syndrome (SIRS) and organ failure but the benefits in this respect of the endovascular approach are unclear. This study evaluated this question and focused on T-cell activation and function. DESIGN: prospective clinical study. MATERIALS: twenty patients undergoing abdominal aortic aneurysm repair (12 C-AAA and 8 E-AAA). METHODS: peripheral T-cell expression of surface markers CD69, CD62L and CD25 in vivo and Interleukin 2 (IL-2) and Interleukin-10 (IL-10) responses to the superantigen staphylococcal enterotoxin B (SEB) in vitro were measured preoperatively, 24 h and 1 week postoperatively. RESULTS: there was no significant increase (p=0.23) in the incidence of SIRS in the open compared with the endovascular group. Enhanced T cell activation occurred following C-AAA and this was associated with significantly greater IL-2 production in response to SEB, with no change in IL-10 production. CONCLUSIONS: E-AAA attenuates proinflammatory T-cell changes compared with C-AAA repair. A reduction in T-cell activation and impaired responsiveness to superantigen suggests that the immunological sequelae of the endovascular approach to aneurysm repair is more favourable than after the open approach with potentially less risk of adverse outcomes. Proof of this thesis will require a larger prospective study.
The use of neoadjuvant chemoradiotherapy prior to surgery in the treatment of oesophageal adenocarcinoma has increased in recent years, and up to 25% of patients will have a complete pathological response to the neoadjuvant therapy. Many patients will not respond, however, and the knowledge of molecular factors predicting response or resistance to chemoradiotherapy is required to enhance treatment results. An understanding of apoptosis and cell proliferation may be relevant and this study focused on apoptotic indices and cell-cycle related (Ki-67, p53 and bcl-2) protein expression in a cohort of 42 patients with primary oesophageal adenocarcinoma. We documented that apoptosis occurs among viable (proliferating) tumour cells in all adenocarcinoma cases examined in this study. Pre-operative chemoradiotherapy significantly increased apoptosis and significantly decreased cell proliferation (estimated by Ki-67 expression). Immunohistochemically detected p53 and bcl-2 gene products had no regulatory role in the apoptotic process. The cumulative expression of p53 protein is significantly associated with increasing proliferation activity. Evaluation of apoptosis in pre-treatment specimens may have potential utility in predicting the efficacy of treatment. Assessment of the tumours proliferation activity by Ki-67 expression might identify patients who are at risk of developing metastatic disease.
Vascular closure staples (VCS) provide a novel technique for fashioning vascular anastomoses, allowing a single operator to perform suture-less anastomoses. They may be used primarily or in an adjuvant role. When VCS are compared to a running suture, advantages include the avoidance of intimal damage, platelet aggregation and intimal hyperplasia at the anastomotic suture line, and a shorter time taken to complete the anastomosis. We report our early experience using VCS in an array of vascular anastomoses and conclude that VCS are a useful addition to the vascular surgeon's armamentarium. They help to decrease the time taken to construct an anastomosis, and are particularly useful in an adjuvant setting, complementing conventionally placed sutures.
BACKGROUND: Primary hyperparathyroidism affects 1 in 700 individuals in the United States. A single adenoma is responsible in over 85% of cases. Surgery remains the most effective treatment. This study was designed to assess the feasibility of minimally invasive radioguided parathyroidectomy (MIRP) with confirmation of excision by ex vivo radioactivity alone. METHODS: Seventy-five consecutive patients with primary hyperparathyroidism were prospectively studied. Following sestamibi scan, patients underwent unilateral neck exploration guided by a handheld gamma probe, which was also used to measure ex vivo radioactivity of excised tissue. RESULTS: The sestamibi scan was positive in 88% of the patients. A small incision (mean, 3.2+/-0.3 cm) was sufficient. Ectopic gland sites were localized in five patients with positive scans and single adenomas. Mean operative time was 48 minutes (range, 15-125 minutes), with shorter procedures after the initial 20 cases (mean, 24 vs. 72 minutes; P < .01). Radioguided parathyroidectomy was successful in 97%, with a mean follow-up of 11 months (range, 1-26 months). As noted previously, adenomatous parathyroid glands contained more than 20% of the background radioactivity. CONCLUSIONS: MIRP is a feasible alternative to bilateral dissection with the advantages of guided dissection and rapid confirmation, and may become the procedure of choice for primary hyperparathyroidism.
OBJECTIVES: transfemoral endoluminal aortic management (TEAM) is technically feasible in the treatment of infrarenal abdominal aortic aneurysms but its advantage over conventional repair is unproved. We report our initial experience, learning curve and technical difficulties encountered during the process of establishing this novel technique in our institute. MATERIAL AND METHODS: over a 3-year period 400 cases of abdominal aortic aneurysms were reviewed; only 58 cases (15%) were suitable for endovascular repair under our TEAM protocol and 36 (9%) were offered endovascular intervention. They were mainly high-risk patients (85% ASA III and IV) with a mean age of 72 years. Thirty-three bifurcated grafts, two straight tube grafts and one aorto mono-iliac graft were deployed. We oversized the graft by 15-20% to the diameter of the aortic neck and both common iliac arteries. RESULTS: two cases (6%-95% CI: 1-19%) had on-table conversion because of ruptured common iliac arteries. Peri-operatively there were two deaths from multi-organ failure. Transient renal failure occurred in two patients and three patients (9%) suffered a non-fatal myocardial infarction. Sixteen percent of patients had a groin wound problem. The mean hospital stay was 7 days. Five minor endoleaks (15%) were identified and sealed at 30 days. One secondary endoleak was identified at 18 months because of a patent juxta-renal lumbar artery. No secondary cuffs or extensions were used. Mean follow-up was 29 months and all grafts remained patent. The technical, clinical, continuous and secondary success rates were 78%, 91%, 89% and 91% respectively with TEAM. CONCLUSION: endovascular training, patient selection and learning curve impose an impact on the final outcome. Until a reliable hard point is reached so that endovascular repair could be exercised in routine practice, the use of TEAM must be questioned in high-risk patients, and should be performed under clinical trial conditions using strict selection criteria.
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Our aims were to determine the incidence of gallstones in a cohort of patients infected with hepatitis C for 20 years, and to analyse the outcome of all patients infected with hepatitis C undergoing laparoscopic cholecystectomy. A hepatitis C screening programme in place in Ireland since 1994 identified 965 patients with hepatitis C antibodies out of 62,667 patients screened. The hepatology unit of Cork University Hospital has 318 patients with hepatitis C. Of patients identified by screening, 201 were post partum women infected via contaminated Anti-D immunoglobulin administered in 1977. Thirty-five (17.4%) of two hundred and one patients with hepatitis C since 1977 had developed gallstones after twenty years. A total of 34 patients with hepatitis C underwent laparoscopic cholecystectomy. One patient required conversion to open cholecystectomy. There were no complications and no mortality. There was a low rate of cirrhosis (11%) on examining liver histology. The incidence of gallstones in a cohort of patients infected with hepatitis C for twenty years approximates to that of the general population. The low rate of cirrhosis in this group may be related to a low consumption of alcohol. Laparoscopic cholecystectomy is a safe procedure in patients with mild chronic liver disease caused by hepatitis C.
Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating glucocorticoids and interleukin-6 (IL-6) have been observed in cancer patients with cachexia and are implicated as major mediators in this process. The purpose of this study was to investigate the role of circulating glucocorticoid levels as primary mediators in cancer-induced cachexia. We evaluated whether inhibition of glucocorticoids with the receptor antagonist RU-486 could abrogate the detrimental wasting of muscle and adipose tissues seen in a well-characterized murine tumor-induced cachexia model. Mice (12/group) were randomized to control, tumor-bearing, control + vehicle, or tumor-bearing + glucocorticoid receptor antagonist groups. Circulating serum glucocorticoid and IL-6 levels were measured in addition to multiple body composition parameters, such as total body weight, lean body mass, and adipose content. The results of this study indicate a significant physiological alteration in the tumor-bearing host that causes severe and detrimental changes in body composition parameters. Regression analysis demonstrated a significant correlation between increased circulating glucocorticoid levels and alterations in body composition parameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the untoward effects of tumor-induced cachexia are not mediated primarily by the peripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.
Gene therapy may allow targeted delivery of tumoricidal drugs to treat pancreatic cancer. Cytosine deaminase (CD) is a bacterial enzyme that converts the nontoxic agent 5-fluorocytosine (5FC) to the active chemotherapeutic agent 5-fluorouracil (5FU). Neoplastic cells induced to express the CD gene treated with 5FC may generate locally high concentrations of 5FU while minimising systemic toxicity. Replication deficient adenovirus vector carrying the CD gene (AdCMV.CD) was tested for therapeutic efficacy against the murine pancreatic carcinoma cell line Pan02. Pan02 cells were infected in vitro with AdCMV.CD or null vector (Ad.-Null) and were examined for expression of CD messenger RNA (mRNA) (Northern blot) and CD enzymatic function (spectrophotometry). mRNA transcripts of the CD gene increased in a dose-dependent manner after infection with AdCMV.CD. Conversion of 5FC to 5FU at a multiplicity of infection (MOI) of 20 was measured to be 51% after a 48-hr incubation. Growth inhibition was measured by MTT assay and thymidine uptake. Pan02 growth in vitro treated with AdCMV.CD and 5FC was inhibited by 80% as compared to cells treated with Ad.Null and 5FC. An in vivo model of pancreatic cancer was established by injecting 2.5 x 10(5) PAN02 cells subcutaneously into the flanks of C57BL/ 6 mice. Seven days later AdCMV.CD was injected into each tumor and 5FC was administered for 10 days. Treatment of mice with AdCMV.CD and 5FC inhibited tumor growth compared to mice who received AdCMV.CD only or 5FC only. These data demonstrate the therapeutic efficacy of an enzyme prodrug strategy in experimental pancreatic cancer.
We conducted a prospective study into patient comprehension of orthopaedic terminology that commonly appears on consent forms. The majority of patients questioned were unsure of the meaning of simple terms such as 'fracture reduction' or 'internal fixation'. All the patients questioned had signed consent forms recently for such procedures in an acute orthopaedic unit. We conclude that many patients willingly consent to procedures that they do not fully understand. This implies that there is an element of trust involved in the process of giving consent. We believe that this aspect of the doctor-patient relationship should be legally respected.
BACKGROUND: The epidermal growth factor (EGF) signal transduction pathway, frequently activated in pancreatic cancer, is an important regulator of cellular growth and transformation. This study examined whether activation of the cyclic adenosine monophosphate protein kinase A pathway may inhibit the EGF signal transduction pathway in pancreatic cancer cell lines. METHODS: Human pancreatic cancer lines BxPC-3 and AsPC-1 were stimulated with EGF, forskolin, or both. Forskolin is a compound that increases cyclic adenosine monophosphate levels. Assays of cell lines were then obtained for cellular growth (MTT assay), anchorage-independent growth (soft agar), and EGF-induced mitogen-activated protein kinase activation as measured by an in-gel kinase assay. RESULTS: Treatment with forskolin resulted in inhibition of EGF-induced activation of mitogen-activated protein kinase activity (BxPC-3 78% inhibition and AsPC-1 70% inhibition, p < 0.005), diminished cellular proliferation (BxPC-3 92% inhibition and AsPC-1 86% inhibition, p < 0.001), and formation of colonies in soft agar (BxPC-3 98% inhibition and AsPC-1 76% inhibition, p < 0.001). Forskolin did not inhibit EGF receptor autophosphorylation or tyrosine kinase signaling in response to EGF. CONCLUSIONS: Forskolin-induced inhibition of mitogen-activated protein kinase is associated with diminished pancreatic cancer cell proliferation in vitro. Use of strategies to increase cyclic adenosine monophosphate levels may have therapeutic application in pancreatic cancer.
BACKGROUND: Gastric carcinoma is a significant cause of death in Ireland. Surgery offers the best option of cure, but the five-year survival following resection remains dismal at 10-15%. Experience from Japan and from some Western units suggest that an extended (D2) lymphadenectomy in association with gastrectomy increases the prospect of cure, but concern about the morbidity and mortality of this operation and lack of evidence from randomised studies has limited its acceptance. AIMS: This study reports the experience of a specialist upper gastrointestinal unit with D2 gastrectomy in a four-year audit. METHODS: Sixty-two resections were performed for gastric cancer. RESULTS: Nineteen patients were deemed unsuitable for the D2 procedure and underwent a more limited lymphadenectomy (D0 or D1). Forty-three patients underwent D2 resection, 12 with an oesophagogastrectomy, 22 with total gastrectomy and nine with a sub-total distal resection. Eight patients undergoing D2 resection had extended resections, five with splenectomy and three with a distal pancreatectomy. Post-operative complications occurred in 31% of patients. Thirty-day and 90-day mortality were zero. Median survival was 822 days in the D2 group (range 120-1,320). CONCLUSIONS: These results show that a D2 gastrectomy can be performed with a low morbidity and mortality and a median survival of greater than two years.
Laparoscopy has been described as being safe and effective in the diagnosis and treatment of Meckel's Diverticulum. We describe the use of laparoscopy in the diagnosis and resection of a Meckel's diverticulum in a 13 year old girl.
Clearly, arginine has great potential as an immunomodulator and may prove useful in catabolic conditions such as severe sepsis and postoperative stress. there is a body of evidence suggesting that supplemental arginine upregulates immune function and reduces the incidence of postoperative infection. More modest improvements in nitrogen balance have been observed. Tumor response to arginine appears to depend on the immunogenicity of the particular tumor and on the requirement of arginine by the tumor as a growth substrate. Of note, ornithine shares the thymotrophic, immunostimulatory and secretagogue effects of arginine. It is, therefore, likely that these compounds share the same cellular mechanism of action or that arginine acts via increasing the concentration of available ornithine. The role of arginine in the injured patient and in the tumor-bearing host demands additional study based on the promising experimental evidence regarding the supplemental use of arginine.
We hypothesize that adenovirus (Ad) vector-mediated delivery of the human interleukin-2 (IL-2) cDNA (AdIL2) or the murine IL-12 cDNA heterodimer (AdIL12) would produce high concentrations of cytokines in the local hepatic milieu to induce host responses sufficient to inhibit the growth of experimental colon carcinoma-derived hepatic metastases. Ad vectors administered intravenously, which is a route known to deliver >90% of the vector to the hepatic parenchyma, achieved significant levels of each cytokine locally, with minimal levels in the sera. To examine the therapeutic effect, the AdIL2 and AdIL12 vectors were evaluated in a hepatic metastasis model that was established by injecting 3 x 10(4) cells from the poorly immunogenic syngeneic C26 colon carcinoma cell line into the right lobe of the livers of BALB/c mice. Animals received AdIL2, AdIL12, or control virus (10(8) plaque-forming units each) intravenously for 2 days after tumor implantation, and tumor growth was compared with naive controls. The AdNull control tumors measured 116 +/- 25 mm2 at 2 weeks. The control virus showed no significant antitumor effect. In marked contrast, both AdIL2 and AdIL12 vectors that were delivered regionally had significant antitumor effects, with AdIL2-treated animals having an average tumor size of 16 +/- 8 mm2; AdIL12-treated tumors measured 6 +/- 6 mm2 (P < .01, both compared with control). Both the AdIL2 and AdIL12 vectors provided a significant survival advantage by log-rank analysis (P < .01), but only AdIL12 translated into an increase in mean survival from 27 (naive control) to 37 days. To evaluate whether these antitumor effects were T-cell-mediated, splenocytes from AdIL2-treated, AdIL12-treated, and naive control groups were stimulated in vitro with gamma-irradiated C26 tumor cells for 5 days and tested for C26 tumor cell cytolysis by an in vitro cytotoxicity assay. Splenocytes from both AdIL2- and AdIL12-treated animals showed a dose-dependent, T-cell-mediated, specific cytolysis of CT26 cells. AdIL12 and to a lesser extent AdIL2 induced natural killer cell activity, as determined by a dose-dependent increase in lysis of the natural killer-specific target cell YAC-1. Overall, these data suggest that regional Ad-mediated delivery of IL-2 and IL-12 cDNAs may be useful for local tumor control and may warrant further investigation as a potentially useful adjuvant for the treatment of hepatic micrometastasis.
This paper documents the various causes of upper limb ischemia in a series of 64 Egyptian patients presenting to a tertiary referral center over a 4-year period and offers a diagnostic dissertation and review of the pertinent literature. Atraumatic upper limb ischemia is an uncommon entity. It has a broad etiology with diverse management pathways. Nineteen patients presented with severe and immediate limb-threatening ischemia. These patients underwent immediate surgical exploration: an embolus was diagnosed in 15 and thrombosis in 4. Twenty-eight patients presented with ischemia of lesser severity, allowing preoperative angiography. Of these 28 patients, 6 had an embolus, 14 had thrombosis, 4 had thoracic outlet syndrome, the remainder had miscellaneous causes. Fifteen patients had upper limb ischemia secondary to arteritis, and 2 patients with dissection of the ascending thoracic aorta presented with upper limb ischemia. Forty-seven patients underwent a surgical procedure, with a morbidity rate of 21% and mortality rate of 19%. Patients presenting with upper limb ischemia tend to have significant co-existing disease. Management of upper limb ischemia requires preoperative and/or peroperative angiography with careful application of vascular surgical expertise.
Malnutrition, a common problem in cancer patients, adversely affects survival and quality of life. It results from several factors that alter nutritional intake and cause massive metabolic disturbances. Anticancer therapies may compound the malnutrition. Optimal nutrition improves therapeutic modalities and the clinical course and outcome. Oral nutrition should be used whenever possible; in patients unable to ingest adequate amounts orally, enteral and parenteral feedings are safe and effective.