Low section of the rectum during laparoscopic total mesorectal excision using the Contour device. Technical report.
Explore the source record for details and available documents.
Equipment Design↗
Biomedical subjects
C Balagué
Publications and source records attributed to C Balagué.
Predictive factors for successful laparoscopic splenectomy in immune thrombocytopenic purpura: study of clinical and laboratory data.
BACKGROUND: Laparoscopic splenectomy (LS) offers better short-term results than open surgery for the treatment of immune thrombocytopenic purpura (ITP), but long-term follow-up is required to ensure its efficacy. The remission rate after splenectomy ranges from 49 to 86% and the factors that predict a successful response to surgical management have not been clearly defined. The goal of this study was to determine the preoperative factors that predict a successful outcome following LS. METHODS: From February 1993 to December 2003, LS was consecutively performed in a series of 119 nonselected patients diagnosed with ITP (34 men and 85 women; mean age, 41 years), and clinical results were prospectively recorded. Postoperative follow-up was based on clinical records, follow-up data provided by the referring hematologist, and a phone interview with the patient and/or relative. Univariate and multivariate analyses were performed for clinical preoperative variables to identify predictive factors of success following LS. RESULTS: Over a mean period of 33 months, 103 patients (84%) were available for follow-up with a remission rate of 89% (92 patients, 77 with complete remission with platelet count > 150,000). Eleven patients did not respond to surgery (platelet count < 50,000). Mortality during follow-up was 2.5% (two cases not related to hematological pathology and one case without response to splenectomy). Preoperative clinical variables evaluated to identify predictive factors of response to surgery were sex, age, treatment (corticoids alone or associated with Ig or chemotherapy), other immune pathology, duration of disease, and preoperative platelet count. In a subgroup of 52 patients, we also evaluated the type of autoantibodies and corticoid doses required to maintain a platelet count > 50,000. Multivariate analysis showed that none of the variables evaluated could be considered as predictive factors of response to LS due to the high standard error. CONCLUSION: Long-term clinical results show that LS is a safe and effective therapy for ITP. However, a higher number of nonresponders is needed to determine which variables predict response to LS for ITP.
Adolescent↗
Laparoscopic management of gastric cancer.
Explore the source record for details and available documents.
Gastrectomy↗
Immediate peritoneal response to bacterial contamination during laparoscopic surgery.
BACKGROUND: Several studies have shown that laparoscopic surgery (LS) minimizes surgical trauma and the immune function is better preserved. Another major advantage of LS is the lower incidence of septic complications. However, several in vitro studies have shown that CO(2) severely impairs macrophage physiology. In theory, this would reduce the ability to respond to peritoneal contamination. However, there is some controversy in view of the evidence of a better preserved peritoneal response to sepsis. This study analyzed the early response of the peritoneum to contamination in a CO(2) ambience. METHODS: A total of 192 CD-1 mice were distributed in three groups: group 1, laparotomy (LAP, n = 64); group 2, CO(2) laparoscopy (CO(2)-LC, n = 64); and group 3, wall lift laparoscopy (WL-LC, n = 64). Mice in each group were randomized to receive 1 ml of Escherichia coli suspension (1 x 10(4) colony-forming units/ml) or saline. Peritoneal fluid was obtained at 1.5, 3, 6, and 12 h after surgery. Monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), and prostaglandin E(2) (PGE(2)) were measured. RESULTS: MCP-1 levels were significantly greater and higher earlier in group 2 (CO(2)-LC) than in group 1 (LAP) (p < 0.007). Simultaneously, the increment in the traction group (WL-LC, group 3) was significantly higher (p < 0.002) than after laparotomy, with no differences in group 2 (CO(2)-LC). When a contamination was added to the laparotomy subgroup, there was a significant increase compared to the group without contamination (p < 0.5). MCP-1 modifications after contamination in the LAP group were statistically significant and appeared later than in the WL-LC (p < 0.002) and CO(2)-LC groups (p < 0.02). For IL-6, the three models presented a significant increase in the noncontaminated groups. This occurred significantly later in the LAP group. Simultaneously, the increase in IL-6 occurred earlier and was significantly higher in the WL-LC group compared to the LAP group (p < 0.003), without differences between CO(2)-LC and wall lift groups. Significant differences between contaminated and noncontaminated subgroups were only observed in the LC-CO(2) groups. When contaminated, the traction model sustained a higher and earlier rise in IL-6 levels compared to the LAP and LC-CO(2) groups (p < 0.001). For PGE(2), The three models showed a significant increase in PGE(2) levels in the noncontaminated groups. However, there were no significant differences between them. In the contaminated groups, there was no statistical difference between the groups. CONCLUSION: Despite a transient impairment of the immediate peritoneal response to a septic challenge, the degree of injury with LS is lower than that with open surgery, and abdominal infection can therefore be better controlled.
Abdomen↗
Stenting of obstructing colonic cancer: a real advance or an irrelevance to the laparoscopic surgeon?
Explore the source record for details and available documents.
Colonic Diseases↗
Long-term outcome after laparoscopic splenectomy related to hematologic diagnosis.
BACKGROUND: Laparoscopic splenectomy (LS) has been demonstrated as an effective and safe treatment for hematological disorders requiring spleen removal, especially in cases of normal-sized spleens. However, although results are promising, long-term outcome data are lacking. We reviewed our clinical experience with LS in a series of 255 cases, with particular attention to the long-term outcome related to the disease process requiring LS. METHODS: From February 1993 to October 2003, LS was attempted in 255 patients (100 males and 155 females with a mean age of 45 +/- 19 years) and clinical information was recorded in a prospective database. Indications for splenectomy included idiopathic thrombocytopenic purpura (ITP) (n = 115), HIV-ITP (n = 9), Evans syndrome (n = 6), autoimmune hemolytic anemia (AIHA) (n = 13), hereditary spherocytosis (HS) (n = 19), hematologic malignancy (n = 66), thrombotic thrombocytopenic purpura (n = 1), and others (n = 26). Long-term postoperative follow-up evaluation was obtained through clinical notes, follow-up visits by the referring hematologist, and by phone interviews both with patients and with the referring hematologist. RESULTS: A total of 186 patients (73%) were available for a mean follow-up of 35 months (range, 1-104). Of the ITP patients, 87 (76%) were followed up, with a remission rate of 89% (complete remission in 75%). A similar remission rate was observed in ITP-HIV; in patients available for follow-up (78%), complete remission was achieved in 83%. In Evans, complete remission was achieved in all patients available for follow-up (67%). Clinical response for hemolytic disease ranged between 70% for AIHA and 100% for HS. In the malignant group, the late mortality rate was 22%. The mortality rate in the miscellaneous group was 5%. No cases of splenectomy-related sepsis occurred during follow-up. CONCLUSIONS: LS offers advantages for all types of splenic diseases requiring surgery. It provides not only good clinical short-term outcome but also satisfactory long-term hematological results.
Adult↗
Differential localisation of GFP fusions to cytoskeleton-binding proteins in animal, plant, and yeast cells. Green-fluorescent protein.
The structure and functioning of the cytoskeleton is controlled and regulated by cytoskeleton-associated proteins. Fused to the green-fluorescent protein (GFP), these proteins can be used as tools to monitor changes in the organisation of the cytoskeleton in living cells and tissues in different organisms. Since the localisation of a specific cytoskeleton protein may indicate a particular function for the associated cytoskeletal element, studies of cytoskeleton-binding proteins fused to GFP may provide insight into the organisation and functioning of the cytoskeleton. In this article, we focused on two animal proteins, human T-plastin and bovine tau, and studied the distribution of their respective GFP fusions in animal COS cells, plant epidermal cells (Allium cepa), and yeast cells (Saccharomyces cerevisiae). Plastin-GFP localised preferentially to membrane ruffles, lamellipodia and focal adhesion points in COS cells, to the actin filament cytoskeleton within cytoplasmic strands in onion epidermal cells, and to cortical actin patches in yeast cells. Thus, in these 3 very different types of cells plastin-GFP associated with mobile structures in which there are high rates of actin turnover. Chemical fixation was found to drastically alter the distribution of plastin-GFP. Tau-GFP bound to microtubules in COS cells and onion epidermal cells but failed to bind to yeast microtubules. Thus, animal and plant microtubules appear to have a common tau binding site which is absent in yeast. We conclude that the study of the distribution patterns of microtubule- and actin-filament-binding proteins fused to GFP in heterologous systems should be a valuable tool in furthering our knowledge about cytoskeleton function in eukaryotic cells.
Actin Cytoskeleton↗
Effect of 2,4-dichlorophenoxyacetic acid herbicide on escherichia coli growth, chemical composition, and cellular envelope.
2,4-Dichlorophenoxyacetic acid (2,4-D) is a herbicide widely used in the world and mainly excreted by the renal route in exposed humans and animals. Herbicides can affect other nontarget organisms, such as Escherichia coli. We observed that a single exposure to 1 mM 2,4-D diminished growth and total protein content in all E. coli strains tested in vitro. In addition, successive exposures to 0.01 mM 2,4-D had a toxic effect decreasing growth up to early stationary phase. Uropathogenic E. coli adhere to epithelial cells mediated by fimbriae, adhesins, and hydrophobic properties. 2,4-D exposure of uropathogenic E. coli demonstrated altered hydrophobicity and fimbriation. Hydrophobicity index values obtained by partition in p-xylene/water were 300-420% higher in exposed cells than in control ones. Furthermore, values of hemagglutination titer, protein contents in fimbrial crude extract, and electron microscopy demonstrated a significant diminution of fimbriation in treated cells. Other envelope alterations could be detected, such as lipoperoxidation, evidenced by decreased polyunsaturated fatty acids and increased lipid degradation products (malonaldehyde), and motility diminution. These alterations decreased cell adherence to erythrocytes, indicating a diminished pathogenic capacity of the 2,4-D-exposed E. coli.
2,4-Dichlorophenoxyacetic Acid↗
Identification of a novel pathogen-responsive element in the promoter of the tobacco gene HSR203J, a molecular marker of the hypersensitive response.
The tobacco gene, HSR203J, which is specifically activated during the early steps of incompatible plant/pathogen interactions has been shown to be a molecular marker of the hypersensitive response (HR). It constitutes an ideal model for the identification of HR-responsive cis-regulatory elements. As a first step in the promoter dissection, deletion mutants of the 5' flanking sequence of HSR203J fused to the GUS reporter gene were analyzed. Then, the construction and study of chimeric constructs containing HSR203J promoter fragments fused to a minimal promoter enabled us to identify a 28-bp regulatory element located between -106 and -79 upstream of the transcription initiation site. This element has been shown to be necessary and sufficient for transcriptional activation in response to pathogen. It contains a 10-bp palindrome followed by its imperfect repeat. The mutagenesis of these two sequence elements led to the identification of a 12-bp motif termed HSRE (HSR203 responsive element) responsible for the marked induction of the HSR203J gene during the HR. Since this DNA region did not show any homology with known regulatory sequences, this 12 bp motif corresponds to a novel cis-regulatory element.
Base Sequence↗
Activation of multiple antibiotic resistance in uropathogenic Escherichia coli strains by aryloxoalcanoic acid compounds.
Clofibric and ethacrynic acids are prototypical pharmacological agents administered in the treatment of hypertrigliceridemia and as a diuretic agent, respectively. They share with 2,4-dichlorophenoxyacetic acid (the widely used herbicide known as 2,4-D) a chlorinated phenoxy structural moiety. These aryloxoalcanoic agents (AOAs) are mainly excreted by the renal route as unaltered or conjugated active compounds. The relatedness of these agents at the structural level and their potential effect on therapeutically treated or occupationally exposed individuals who are simultaneously undergoing a bacterial urinary tract infection led us to analyze their action on uropathogenic, clinically isolated Escherichia coli strains. We found that exposure to these compounds increases the bacterial resistance to an ample variety of antibiotics in clinical isolates of both uropathogenic and nonpathogenic E. coli strains. We demonstrate that the AOAs induce an alteration of the bacterial outer membrane permeability properties by the repression of the major porin OmpF in a micF-dependent process. Furthermore, we establish that the antibiotic resistance phenotype is primarily due to the induction of the MarRAB regulatory system by the AOAs, while other regulatory pathways that also converge into micF modulation (OmpR/EnvZ, SoxRS, and Lrp) remained unaltered. The fact that AOAs give rise to uropathogenic strains with a diminished susceptibility to antimicrobials highlights the impact of frequently underestimated or ignored collateral effects of chemical agents.
Anti-Bacterial Agents↗
Human papillomavirus E6E7-mediated adenovirus cell killing: selectivity of mutant adenovirus replication in organotypic cultures of human keratinocytes.
Replication-competent adenoviruses are being investigated as potential anticancer agents. Exclusive virus replication in cancer cells has been proposed as a safety trait to be considered in the design of oncolytic adenoviruses. From this perspective, we have investigated several adenovirus mutants for their potential to conditionally replicate and promote the killing of cells expressing human papillomavirus (HPV) E6 and E7 oncoproteins, which are present in a high percentage of anogenital cancers. For this purpose, we have employed an organotypic model of human stratified squamous epithelium derived from primary keratinocytes that have been engineered to express HPV-18 oncoproteins stably. We show that, whereas wild-type adenovirus promotes a widespread cytopathic effect in all infected cells, E1A- and E1A/E1B-deleted adenoviruses cause no deleterious effect regardless of the coexpression of HPV18 E6E7. An adenovirus deleted in the CR2 domain of E1A, necessary for binding to the pRB family of pocket proteins, shows no selectivity of replication as it efficiently kills all normal and E6E7-expressing keratinocytes. Finally, an adenovirus mutant deleted in the CR1 and CR2 domains of E1A exhibits preferential replication and cell killing in HPV E6E7-expressing cultures. We conclude that the organotypic keratinocyte culture represents a distinct model to evaluate adenovirus selectivity and that, based on this model, further modifications of the adenovirus genome are required to restrict adenovirus replication to tumor cells.
Adenoviridae↗
Hand-assisted laparoscopic splenectomy.
Hand-assisted laparoscopic surgery (HALS) permits recovery of the tactile sensation and facilitates manipulation of solid organs. Our preliminary experience in laparoscopic splenectomy (LS) shows its advantages, with a substantial reduction of operative time, while maintaining the advantages of a less aggressive surgical approach. The role of HALS in cases of splenomegaly or trauma seems to be clear. It can also be considered as an alternative to conventional conversion in cases of intraoperative complications or unclear anatomy. The role of HALS for normal-sized spleens is more controversial because there is a well-systematized, conventional LS technique available, which is followed by optimal clinical outcome LS in hands of a skilled surgeon.
Adult↗
Sustained high-level expression of full-length human factor VIII and restoration of clotting activity in hemophilic mice using a minimal adenovirus vector.
The successful prophylactic treatment of hemophilia A by frequent infusions of plasma concentrates or recombinant factor VIII (hFVIII) indicates that gene therapy may be a potential alternative for the treatment of the disease. For efficient delivery and long-term expression of the hFVIII gene, a novel minimal adenovirus (mini-Ad) vector, MiniAdFVIII, has been developed. The vector is devoid of all viral genes and carries the full-length hFVIII cDNA under the control of the human 12.5-kb albumin promoter. The MiniAdFVIII vector was propagated with the assistance of an ancillary vector in 293 cells and was purified by CsCl banding. Sustained expression of hFVIII at physiologic levels (100-800 ng/mL) was achieved in mice after a single intravenous injection of MiniAdFVIII. The expressed hFVIII had a structure identical to that of recombinant hFVIII, as determined by Western blot analysis. The functionality of the protein was confirmed by the restoration of blood coagulation capacity in MiniAdFVIII-treated hemophilic mice, as determined by tail clipping observations. Although antivector or antihuman FVIII antibodies at various levels were detected, long-term expression of the transgene was observed in the mice that did not generate antibodies against the transgene product. The vector DNA persisted in the liver tissues of the mice with long-term expression. No significant histopathologic findings or toxicities were observed to be associated with the vector in the MiniAdFVIII-treated C57BL/6 mice. These results support the further development of MiniAdFVIII for clinical trials toward the treatment of hemophilia A.
Adenoviridae↗
Could age be an indication for laparoscopic colectomy in colorectal cancer?
BACKGROUND: The incidence of colorectal carcinoma increases in the elderly. Regardless of age as an isolated factor, postoperative complications represent the main factor in increasing hospital mortality. METHODS: The aim of this study was to compare the short-term results (first 30 postoperative days) after laparoscopically assisted colectomy (LAC) and open segmental colectomy (OC) in colorectal carcinoma between two groups of patients, older than 70 and younger than 70 years of age. In the study from November 1993 to June 1998, 255 patients were evaluated to participate. RESULTS: Peristalsis, oral intake, and discharge from the hospital occurred earlier in LAC than in OC treated patients, in the two age groups. The mean operative time was significantly longer in the LAC than in the OC patients in the two age groups. No differences were observed in morbidity between LAC and OC in the group younger than 70 years of age. However, the overall morbidity was significantly lower in the LAC group in patients older than 70 years. One patient in the LAC group older than 70 years died. CONCLUSION: These results suggest that laparoscopically assisted colectomy may be particularly indicated in elderly patients.
Age Factors↗
Replicative adenoviruses for cancer therapy.
Rapid advances are being made in the engineering of replication-competent viruses to treat cancer. Adenovirus is a mildly pathogenic human virus that propagates prolifically in epithelial cells, the origin of most human cancers. While virologists have revealed many details about its molecular interactions with the cell, applied scientists have developed powerful technologies to genetically modify or regulate every viral protein. In tandem, the limited success of nonreplicative adenoviral vectors in cancer gene therapy has brought the old concept of adenovirus oncolysis back into the spotlight. Major efforts have been directed toward achieving selective replication by the deletion of viral functions dispensable in tumor cells or by the regulation of viral genes with tumor-specific promoters. However, the predicted replication selectivity has not been realized because of incomplete knowledge of the complex virus-cell interactions and the leakiness of cellular promoters in the viral genome. Capsid modifications are being developed to achieve tumor targeting and enhance infectivity. Cellular and viral functions that confer greater oncolytic potency are also being elucidated. Ultimately, the interplay of the virus with the immune system will likely dictate the success of this approach as a cancer therapy.
Adenoviridae↗
hxc2, an Arabidopsis mutant with an altered hypersensitive response to Xanthomonas campestris pv. campestris.
A chemical mutagenized population of Arabidopsis Col-0-gl plants was screened for an altered hypersensitive response (HR) after spray inoculation with an HR-inducing isolate of Xanthomonas campestris pv. campestris (strain 147). Three classes of mutant were identified: those exhibiting an HR- phenotype or partial loss of HR; hyper-responsive mutants showing necrotic lesions rapidly leading to the collapse of leaves; and susceptible mutants. One mutant belonging to the susceptible class, hxc-2, was extensively characterized. The compatible phenotype observed several days after initiation of the interaction was confirmed by measurement of in planta bacterial growth and use of bacterial strains constitutively expressing the GUS reporter gene. In the same way, accumulation of autofluorescent compounds, salicylic acid production and defence gene expression in the mutant were found to be similar to that displayed by the susceptible ecotype. Inoculation of hxc-2 with different avirulent bacteria suggests that the mutation is specific for the interaction with the Xcc 147 strain, although the mutation has been shown to affect a single dominant locus, different from the resistance locus defined by genetic analysis of resistance to Xcc 147. Genetic mapping of the mutation indicated that it is located on chromosome III, defining a previously unknown resistance function in response to X. c. campestris.
Arabidopsis↗
Laparoscopic surgery and surgical infection.
INTRODUCTION: It has been observed that the metabolic response to surgical injury is less after laparoscopic surgery than after open surgery. However, the effect of laparoscopic surgery on surgical infection has not been given much attention in the surgical literature, even though it may decrease the incidence of infectious complications. The objective of this study was to assess the influence that laparoscopic surgery has on surgical infection and to highlight certain controversial aspects. METHODS: A review of the literature was undertaken to examine the relationship between laparoscopic surgery and surgical infection. This was achieved primarily by using PubMed Medline as a source of material. RESULTS AND CONCLUSION: Laparoscopic surgery is associated with better preservation of the immune system than open surgery. This results in a decreased incidence of infectious complications. Although carbon dioxide pneumoperitoneum affects the peritoneal response to injury, it seems to have no harmful effect in terms of intra-abdominal infection. Nevertheless, at laparoscopic operation the virulence of intestinal micro-organisms should be recognized and, while knowing the advantages of minimally invasive surgery, the surgeon should consider the complexity of this technique. Furthermore, maintenance of laparoscopic instruments should be governed by the same norms as those used in open surgery; recommendations offered by the manufacturers should be respected.
Equipment Contamination↗
Gene therapy for gliomas: molecular targets, adenoviral vectors, and oncolytic adenoviruses.
Currently, most of the approved clinical gene therapy protocols involve cancer patients and several of the therapies are designed to treat brain tumors. Two factors promoting the use of gene therapy for gliomas are the failure and toxicity of conventional therapies and the identification of the genetic abnormalities that contribute to the malignancy of gliomas. During the malignant progression of astrocitic tumors several tumor suppressor genes are inactivated, and numerous growth factors and oncogenes are overexpressed progressively. Thus, theoretically, brain tumors could be treated by targeting their fundamental molecular defects, provided the gene-drug can be delivered to a sufficient number of malignant cells. However, gene therapy strategies have not been abundantly successful clinically, in part because the delivery systems are still imperfect. In the first part of this brief review we will discuss the most common targets for gene therapy in brain tumors. In the second part, we will review the evolution of adenoviruses as gene vehicles. In addition, we will examine the role of recombinant mutant oncolytic adenoviruses as anticancer tools. From the results to date it is clear that gene therapy strategies for brain tumors are quite promising but more critical research is required, mainly in the vector field, if the strategies are to achieve their true potential in ameliorating patients with gliomas.
Adenoviruses, Human↗