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Biomedical subjects

T Ellis

Publications and source records attributed to T Ellis.

At least 19 recordsLinked to original sources

Hematogenous spread as a mechanism for the generation of abdominal wound metastases following laparoscopy.

BACKGROUND: We designed this study to determine whether hematogenous spread has a role in the etiology of port site metastases following laparoscopic surgery. METHODS: The study design had two parts. In experiment 1, two groups (n = 30) of male Dark Agouti rats were studied. Under general anesthesia, the first group (20 rats) underwent 15 mins of laparoscopic insufflation, followed by an injection of a suspension of 105 Dark Agouti mammary adenocarcinoma (DAMA) cells into the internal jugular vein and a further 15-mins period of insufflation. The laparoscopic ports were then removed, and the wounds were closed and marked. In the second group (n = 10), the procedure was identical except that a 2.5-cm midline laparotomy was performed 15 mins after the commencement of anesthesia and insufflation was not used. The laparotomy was closed in two layers. In experiment 2, one group (n = 4) was studied. The study protocol was identical to the first laparoscopic group except that a larger number of 106 DAMA cells were injected. All rats in both experiments were killed 15 days later, and the injection site, laparoscopy wounds, and laparotomy wound were examined histologically by a blinded histopathologist. RESULTS: In experiment 1, one port site tumor was detected in the laparoscopic group and no wound metastases were found in the laparotomy group. Postoperative weight loss was significantly less in the laparoscopic group (p < 0.001). In experiment 2, no port site metastases were detected. CONCLUSION: Although hematogenous spread is a possible mechanism in the development of port site metastases, judging from the low number of port site metastases in this study as compared to previous reports using this tumor model, this mechanism is unlikely to be a major contributor to the problem of wound metastasis following laparoscopy.

Abdomen↗

The transcriptional repressor CDP (Cutl1) is essential for epithelial cell differentiation of the lung and the hair follicle.

The mammalian Cutl1 gene codes for the CCAAT displacement protein (CDP), which has been implicated as a transcriptional repressor in diverse processes such as terminal differentiation, cell cycle progression, and the control of nuclear matrix attachment regions. To investigate the in vivo function of Cutl1, we have replaced the C-terminal Cut repeat 3 and homeodomain exons with an in-frame lacZ gene by targeted mutagenesis in the mouse. The CDP-lacZ fusion protein is retained in the cytoplasm and fails to repress gene transcription, indicating that the Cutl1(lacZ) allele corresponds to a null mutation. Cutl1 mutant mice on inbred genetic backgrounds are born at Mendelian frequency, but die shortly after birth because of retarded differentiation of the lung epithelia, which indicates an essential role of CDP in lung maturation. A less pronounced delay in lung development allows Cutl1 mutant mice on an outbred background to survive beyond birth. These mice are growth-retarded and develop an abnormal pelage because of disrupted hair follicle morphogenesis. The inner root sheath (IRS) is reduced, and the transcription of Sonic hedgehog and IRS-specific genes is deregulated in Cutl1 mutant hair follicles, consistent with the specific expression of Cutl1 in the progenitors and cell lineages of the IRS. These data implicate CDP in cell-lineage specification during hair follicle morphogenesis, which resembles the role of the related Cut protein in specifying cell fates during Drosophila development.

Alleles↗

A prospective randomized trial of laparoscopic Nissen fundoplication with anterior vs posterior hiatal repair.

HYPOTHESIS: The technique used for repair of the esophageal hiatus during laparoscopic Nissen fundoplication can influence the likelihood of postoperative dysphagia. DESIGN: A prospective double-blind randomized control trial. SETTING: A university teaching hospital. PARTICIPANTS: A total of 102 patients with proven gastroesophageal reflux disease, undergoing a laparoscopic Nissen fundoplication were randomized to undergo fundoplication with either anterior (47 patients) or posterior (55 patients) repair of the diaphragmatic hiatus. Patients were excluded for the following reasons: they had esophageal motility disorders, required a concurrent abdominal procedure, had undergone previous antireflux surgery, or had very large hiatus hernias. INTERVENTIONS: Laparoscopic Nissen fundoplication with anterior vs posterior hiatal repair. MAIN OUTCOME MEASURES: Independent assessment of dysphagia, heartburn, patient satisfaction, and other symptoms 1, 3, and 6 months following surgery, using multiple standardized clinical grading systems. Objective measurement of lower esophageal sphincter pressure, esophageal emptying time, distal esophageal acid exposure, and endoscopic assessment of postoperative anatomy and esophageal mucosa. RESULTS: Symptoms of postoperative dysphagia, relief of heartburn, and overall satisfaction 6 months after surgery were not influenced by the hiatal repair technique. However, to achieve a similar incidence of dysphagia, more patients who initially underwent posterior hiatal repair required a second surgical procedure (6 vs 0 patients). The hiatal repair technique did not affect the likelihood of early postoperative paraesophageal herniation. CONCLUSION: Anterior suturing of the hiatus appears to be at least as good in the short-term as posterior suturing as a method of narrowing the hiatus during laparoscopic Nissen fundoplication.

Adult↗

Nitric oxide production by coelomocytes of Asterias forbesi.

Vertebrate mononuclear phagocytes produce a plethora of molecules involved in host defense. Among the most potent are the reactive oxygen and nitrogen intermediates. Coelomocytes from invertebrates subserve many of the same functions. In order to determine whether invertebrate phagocytes employ reactive nitrogen intermediates, we investigated the effect of various nonspecific stimulators and invertebrate interleukin (IL)-1alpha- and beta-like molecules on nitric oxide (NO) production. Elevated NO release by stimulated coelomocytes was seen after 24 h. Incubation of stimulated coelomocytes in the presence of arginine analogs inhibited NO release. When invertebrate IL-1-like molecules were added to the coelomocytes, they stimulated the release of NO. Western blot analysis using a polyclonal rabbit antiserum to murine NO synthase detected a band at approximately 125 kDa. These data indicate that coelomocytes are capable of producing and releasing NO and that NO is a chemical mediator that has been conserved as a host defense weapon of phagocytes through evolutionary time.

Animals↗

Metabolic and immunologic consequences of laparoscopy with helium or carbon dioxide insufflation: a randomized clinical study.

BACKGROUND: Previous studies using animal models have demonstrated that carbon dioxide (CO2) pneumoperitoneum during laparoscopy is associated with adverse physiological, metabolic, immunological and oncological effects, and many of these problems can be avoided by the use of helium insufflation. The present study was performed in patients to compare the effect of helium and CO2 insufflation on intraperitoneal markers of immunological and metabolic function. METHODS: Eighteen patients undergoing elective upper gastrointestinal laparoscopic surgery were randomized to have insufflation achieved by using either helium (n = 8) or CO2 (n = 10) gas. Intraperitoneal pH was monitored continuously during surgery, and peritoneal macrophage function was determined by harvesting peritoneal macrophages at 5 min and 30 min after commencing laparoscopy, and then assessing their ability to produce tumour necrosis factor-alpha (TNF-alpha), and their phagocytic function. RESULTS: Carbon dioxide laparoscopy was associated with a lower intraperitoneal pH at the commencement of laparoscopy, although this difference disappeared as surgery progressed. The production of TNF-alpha was better preserved by CO2 laparoscopy, but the insufflation gas used did not affect macrophage phagocytosis. Patients undergoing helium laparoscopy required less postoperative analgesia. CONCLUSION: The choice of insufflation gas can affect intraperitoneal macrophage function in the clinical setting, and possibly acid-base balance. The present study suggested no immunological advantages for the clinical use of helium as an insufflation gas. The outcomes of the present study, however, are different to those obtained from previous laboratory studies and further research is needed to confirm this outcome.

Carbon Dioxide↗

Stability boundaries and lateral postural control in parkinson's disease.

Postural instability is a major problem in patients with Parkinson's disease (PD). We examined balance control in PD by using center of pressure (CP) variability and time-to-contact to investigate boundary relevant postural control behavior under quiet stance leaning conditions. Postural orientation was manipulated by having patients (n = 10) and healthy older controls (n = 7) lean forward and backward with varying degrees of lean on a force platform. The subjects were instructed to lean forward or backward (either halfway or as far as possible) without bending their hips or lifting their heels or toes off the ground. Time-to-contact of the CP with the geometric stability boundary defined by the feet as well as CP position and variability were analyzed. Medio-lateral CP variability was increased in the patients with PD. Medio-lateral average time-to-contact was decreased in the patients but not so in the anterior-posterior direction. In contrast to the CP variability, the medio-lateral variability of time-to-contact was lower in the patients. Patients as well as healthy older controls responded to lean manipulations with an increase in CP variability. Boundary relevant CP measures thus show clear changes in control strategies and confirm the role of lateral instability in PD.

Adult↗

Efficient ex vivo transduction of pancreatic islet cells with recombinant adeno-associated virus vectors.

The ability to transfer immunoregulatory, cytoprotective, or antiapoptotic genes into pancreatic islet cells may allow enhanced posttransplantation survival of islet allografts and inhibition of recurrent autoimmune destruction of these cells in type 1 diabetes. However, transient transgene expression and the tendency to induce host inflammatory responses have limited previous gene delivery studies using viral transfer vectors. We demonstrate here that recombinant adeno-associated virus (rAAV) serotype 2, a vector that can overcome these limitations, effectively transduces both human and murine pancreatic islet cells with reporter genes as well as potentially important immunoregulatory cytokine genes (interleukin-4, interleukin-10), although a very high multiplicity of infection (10,000 infectious units/islet equivalent) was required. This requirement was alleviated by switching to rAAV serotype 5, which efficiently transduced islets at a multiplicity of infection of 100. Although adenovirus (Ad) coinfection was required for efficient ex vivo expression at early time points, islets transduced without Ad expressed efficiently when they were transplanted under the renal capsule and allowed to survive in vivo. The rAAV-delivered transgenes did not interfere with islet cell insulin production and were expressed in both beta- and non-beta-cells. We believe rAAV will provide a useful tool to deliver therapeutic genes for modulating immune responses against islet cells and markedly enhance longterm graft survival.

Adenoviridae↗

Influence of gases on intraperitoneal immunity during laparoscopy in tumor-bearing rats.

Laparoscopy has been associated with metastases to abdominal wall wounds. In addition, many recent experimental studies suggest that laparoscopy is associated with increased tumor dissemination. It is possible that immune or metabolic disturbances due to the use of a pneumoperitoneum could contribute to this problem. To investigate this possibility, we studied the effect of two insufflation gases and gasless laparoscopy on in vivo peritoneal macrophage function and intraperitoneal pH in an experimental model. A carcinoma was implanted into the flank of 32 experimental rats that underwent laparoscopic surgery in one of four treatment groups: anesthesia alone, gasless laparoscopy, helium insufflation, and CO2 insufflation. Intraperitoneal pH was monitored during surgery, and peritoneal macrophage function was determined 3 days after surgery by harvesting peritoneal macrophages and then examining their ability to produce tumour necrosis factor-alpha (TNF-alpha). CO2 insufflation was associated with a consistent fall in intraperitoneal pH and a significant reduction in TNFalpha production. These findings did not occur in the other study groups. The results of this study demonstrate that CO2 insufflation results in depressed intraperitoneal macrophage activity. It is possible that it is mediated by pH changes. In addition, it could be a contributing factor to the development of port-site metastases. Further studies are needed to determine whether the factors identified act during clinical surgery.

Animals↗

The effect of immune enhancement and suppression on the development of laparoscopic port site metastases.

BACKGROUND: Recent clinical case reports and experimental studies have suggested that laparoscopic cancer surgery is associated with an increased risk of tumor spread to abdominal wall wounds. While the etiology of this problem was initially believed to be related to mechanical contamination of wounds, it is now recognized that there are other contributory factors, including disturbed immune function within the peritoneal cavity. To investigate this question further, we evaluated the effect of immune modulation within an established laparoscopic cancer model. METHODS: Eighteen immune-competent syngeneic rats underwent modulation of their immune system, followed 18 h later by laparoscopy with the introduction of a suspension of adenocarcinoma cells into the peritoneal cavity. Rats were randomly allocated to receive either systemic cyclosporin (immune suppressor), intraperitoneal endotoxin (immune enhancer), or no agent (controls). Seven days later, all rats were killed and their peritoneal cavity was inspected for tumor implantation and port site metastases. RESULTS: Cyclosporin did not influence the study outcome, but tumor growth (p = 0.008) and port site metastases (p < 0.0001) were less common following the administration of intraperitoneal endotoxin. CONCLUSION: The results of this study suggest that the immune system plays a role in the genesis of port site metastases. A preventive role for endotoxin in patients undergoing laparoscopic cancer surgery, however, remains speculative.

Abdominal Muscles↗

Clozapine and risperidone treatment of psychosis in Parkinson's disease.

The authors compared efficacy and safety of risperidone and clozapine for the treatment of psychosis in a double-blind trial with 10 subjects with Parkinson's disease (PD) and psychosis. Mean improvement in the Brief Psychiatric Rating Scale psychosis score was similar in the clozapine and the risperidone groups (P=0.23). Although the mean motor Unified Parkinson's Disease Rating Scale score worsened in the risperidone group and improved in the clozapine group, this difference did not reach statistical significance. One subject on clozapine developed neutropenia. In subjects with PD, risperidone may be considered as an alternative to clozapine because it is as effective for the treatment of psychoses without the hematologic, antimuscarinic, and seizure side effects. However, risperidone may worsen extrapyramidal symptoms more than clozapine and therefore must be used with caution.

Aged↗

The pharmacokinetics and pharmaco-dynamics of Procysteine in amyotrophic lateral sclerosis.

In 13 subjects with ALS, we studied the safety and pharmacokinetic properties of Procysteine, a cysteine prodrug that increases levels of intracellular glutathione. We found that oral administration of Procysteine was safe. Procysteine enters CSF after both IV and oral dosing and accumulates to significant levels in CSF. We also observed that CSF levels of glutathione fall dramatically with aging.

Administration, Oral↗

Comparison of serological tests and faecal culture for the detection of Mycobacterium avium subsp. paratuberculosis infection in cattle and analysis of the antigens involved.

Three hundred and forty-one sera from cattle in Western Australia and 106 sera from Mycobacterium paratuberculosis faecal culture positive cattle were used to evaluate the performance of two absorbed enzyme-linked immunosorbent assays (ELISA) (one locally produced, the other a commercial test) and a complement fixation test (CFT) for the detection of Johne's disease in cattle. The diagnostic sensitivity (47.2%) of the local ELISA was significantly higher than that of the commercial ELISA (31.1%), and significantly higher than that for the complement fixation test (17.9%) and immunoblot (20.8%). Diagnostic specificity for the two ELISAs was 99.7% and 97.9% and similar for CFT and immunoblot (97.1% and 97.7%, respectively). The diagnostic sensitivity rose for both ELISAs and the CFT as the number of M. paratuberculosis isolated from the faeces increased. The ELISA antigen was characterised by polyacrylamide gel electrophoresis and electrophoretic immunoblotting and was found to consist mostly of a carbohydrate-type macromolecule of 32-42 kDa. This macromolecule was identified as lipoarabinomannan (LAM) by using a LAM-specific monoclonal antibody in immunoblots and purified LAM in absorption experiments. By applying more complex antigen preparations in immunoblots, serum antibodies against proteins of 47, 37, 30, 24 and 21 kDa, and against the 32-42 kDa carbohydrate component were frequently found in infected cattle, and of these the 47 kDa protein and the 32-42 kDa antigen were immuno-dominant. Pre-absorption of the sera with M. phlei sonicate indicated that the protein antigens contributed markedly to non-specific serological cross-reactions, while the 32-42 kDa non-protein macromolecule appeared to be specific.

Animals↗

Influence of cytotoxic agents on intraperitoneal tumor implantation after laparoscopy.

PURPOSE: Recent experimental studies suggest that laparoscopic surgery for abdominal malignancy may be associated with increased tumor implantation. This study investigated the influence of cytotoxic agents (administered intraperitoneally or intramuscularly) on implantation of a tumor cell suspension after laparoscopic surgery in an experimental model. METHODS: Thirty-three Dark Agouti rats underwent laparoscopy with CO2 insufflation and instillation of a tumor cell suspension into the abdominal cavity. Rats were randomly allocated to one of the following study groups (9 rats in the control group, 6 rats in all other groups): 1) control (no intraperitoneal instillation); 2) intraperitoneal normal saline (0.9 percent); 3) intraperitoneal povidone-iodine (Betadine to normal saline 1:10 dilution); 4) intraperitoneal methotrexate (2 doses of 0.125 mg/kg body weight in normal saline administered 24 hours apart); 5) intramuscular injection of 2 doses of 0.125 mg/kg body weight administered 24 hours apart (no intraperitoneal agent). Rats were killed 7 days after the procedure, and the peritoneal cavity and port sites were examined for the presence of tumor. RESULTS: A significant reduction in tumor implantation and port-site metastases was observed in all treatment groups (povidone-iodine and intramuscular and intraperitoneal methotrexate). CONCLUSIONS: This study suggests that tumor implantation after laparoscopic surgery and port-site metastases might be prevented by the intraperitoneal or systemic administration of cytotoxic agents. Further studies are needed to determine whether these findings can be applied to clinical practice.

Animals↗

Experimental study of the effect of intraperitoneal heparin on tumour implantation following laparoscopy.

BACKGROUND: Conclusions drawn from clinical reports of port site metastases following laparoscopic resection of intra-abdominal malignancy are now supported by a burgeoning experimental literature which suggests that laparoscopy promotes tumour metastasis to wounds. This study investigated the effect of intraperitoneal blood and heparin on the incidence of tumour cell implantation and port site metastasis. METHODS: Twenty-four Dark Agouti rats underwent laparoscopy with carbon dioxide insufflation and the instillation of a tumour cell suspension and/or blood into the peritoneal cavity. Rats were allocated randomly to one of the following study groups (six rats per group): (1) controls; (2) intraperitoneal blood (2 ml blood introduced from a syngeneic donor rat); (3) intraperitoneal heparin; (4) intraperitoneal blood and heparin. Rats were killed 7 days after the procedure, and the peritoneal cavity and port sites were examined for the presence of tumour. RESULTS: Tumour implantation and port site metastases were reduced by the intraperitoneal administration of heparin, but increased by the presence of intraperitoneal blood. CONCLUSION: The results of this study suggest that tumour implantation following laparoscopy is promoted by the presence of intraperitoneal blood and that this effect may be reduced by the use of intraperitoneal heparin.

Animals↗

Cellular immune responses against proinsulin: no evidence for enhanced reactivity in individuals with IDDM.

Investigations of humans and nonobese diabetic mice suggest that proinsulin and/or a fragment of the region spanning C-peptide and the B-chain of insulin (i.e., proinsulin peptide) may serve as key autoantigens in IDDM. Therefore, we analyzed cellular immune reactivities against these molecules in people with or at varying risks for the disease to clarify their role in the pathogenesis of IDDM. In vitro peripheral blood mononuclear cell (PBMC) responses against these antigens, a control antigen (tetanus toxoid), and phytohemaglutinin were determined in 60 individuals with newly diagnosed IDDM (< or = 1 day from diagnosis) in 34 islet cell cytoplasmic autoantibody- and/or insulin autoantibody-negative first-degree relatives of the IDDM subjects, and in 28 autoantibody-negative control subjects. Unlike previous reports suggesting diabetes-associated elevations in cellular immunity to other beta-cell antigens (e.g., GAD, IA-2, etc.), we observed equivalent levels of phytohemaglutinin stimulation and cellular proliferation in all groups against these antigens (all P values were not significant). The mean stimulation index +/- SD and frequency of reactivity to proinsulin for healthy control subjects and IDDM patients, respectively, were as follows: 1 microg/ml (1.5 +/- 1.0, 1 out of 17 [6%]; 1.9 +/- 1.4, 4 out of 33 [12%]); 10 microg/ml (1.7 +/- 1.3, 1 out of 17 [6%]; 1.2 +/- 0.6, 0 out of 28 [0%]); and 50 microg/ml (1.2 +/- 0.6, 1 out of 16 [6%]; 1.1 +/- 0.6, 1 out of 27 [4%]). The response in healthy control subjects, autoantibody-negative relatives, and IDDM patients, respectively, against the proinsulin peptide fragment were as follows: 1 microg/ml (0.9 +/- 0.4, 1 out of 12 [8%]; 1.3 +/- 1.1, 4 out of 34 [11%]; 1.1 +/- 0.3, 2 out of 28 [7%]); 10 microg/ml (0.9 +/- 0.6, 1 out of 12 [8%]; 1.2 +/- 0.6, 3 out of 34 [9%] 1.4 +/- 1.7, 2 out of 28 [7%]); and 50 microg/ml (1.0 +/- 0.7, 1 out of 12 [8%]; 1.2 +/- 0.5, 2 out of 34 [6%]; 1.3 +/- 0.5, 2 out of 28 [7%]). Taken together with previous studies reporting relatively infrequent occurrences of autoantibodies to proinsulin, the role of immunity to this molecule in the pathogenesis of IDDM in humans remains unclear.

Adult↗

Medical fitness.

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Humans↗

Bloodborne pathogens: toward safer needles.

California leads the way in protecting workers with sharps injury prevention devices. This article discusses the state's legislation to prevent needlestick injuries among healthcare workers and its impact. A chart to be used as a sharps injury log is provided.

Blood-Borne Pathogens↗