PubMed Health⌕ Search

Biomedical subjects

Paul Ziprin

Publications and source records attributed to Paul Ziprin.

10 recordsLinked to original sources
PubMed2005

A comparison of open vs. laparoscopic abdominal rectopexy for full-thickness rectal prolapse: a meta-analysis.

PURPOSE: Using meta-analytical techniques, this study was designed to compare open and laparoscopic abdominal procedures used to treat full-thickness rectal prolapse in adults. METHODS: Comparative studies published between 1995 and 2003, cited in the literature of open abdominal rectopexy vs. laparoscopic abdominal rectopexy, were used. The primary end points were recurrence and morbidity, and the secondary end points assessed were operative time and length of hospital stay. A random effect model was used to aggregate the studies reporting these outcomes, and heterogeneity was assessed. RESULTS: Six studies, consisting of a total of 195 patients (98 open and 97 laparoscopic) were included. Analysis of the data suggested that there is no significant difference in recurrence and morbidity between laparoscopic abdominal rectopexy and open abdominal rectopexy. Length of stay was significantly reduced in the laparoscopic group by 3.5 days (95 percent confidence interval, 3.1-4; P < 0.01), whereas the operative time was significantly longer in this group, by approximately 60 minutes (60.38 minutes; 95 percent confidence interval, 49-71.8). CONCLUSIONS: Laparoscopic abdominal rectopexy is a safe and feasible procedure, which may compare equally with the open technique with regards to recurrence and morbidity and favorably with length of stay. However large-scale randomized trials, with comparative, sound methodology are still needed to ascertain detailed outcome measures accurately.

Adult↗
PubMed2005

ICAM-1 mediated peritoneal carcinomatosis, a target for therapeutic intervention.

Development of peritoneal metastasis is a significant issue in the treatment of abdominal cancers. Primary interaction between tumour cells and the mesothelium is a vital step in initiating this process. Our aim was to determine the role of the intercellular adhesion molecule-1 (ICAM-1) in mesothelial-tumour adhesion and the effectiveness of therapeutic intervention. Mesothelial cells were derived from omental tissue. ICAM-1 expression in resting state, in the presence of TNF-alpha or after the application of heparin or hyaluronan was determined by flow cytometry. Functional effects on tumour adhesion to a mesothelial monolayer were determined via a Calcein-AM in vitro adhesion assay. In vivo studies were performed utilising 30 WAG/rij rats, which underwent mini-laparotomy with the injection of 1 x 10(5 )CC 513 tumour cells intraperitoneally. Tumour growth was assessed macroscopically and microscopically by two independent examiners. Mesothelial cells expressed high level of ICAM-1, which was up-regulated by the presence of TNF-alpha. The introduction of heparin caused a decrease in ICAM-1 expression, however hyaluronan did not affect the expression. A significant decrease in tumour-mesothelial cell adhesion in vitro and complete aberration of tumour growth in vivo was observed with heparin application. In vitro studies showed utilisation of high molecular weight hyaluronan, which was more limited in vivo. These data imply that heparin may be used as a potential therapeutic through a defined molecular mechanism both in vitro and in vivo. Hyaluronan appears to function as a barrier and hence may be unreliable in blocking peritoneal recurrence.

Animals↗
PubMed2005

Hypoxia augments gelatinase activity in a variety of adenocarcinomas in vitro.

BACKGROUND: Hypoxia within solid adenocarcinomas and protease up-regulation has been independently implicated as poor prognostic indicators in a variety of tumor types. The authors hypothesize that Matrix Metalloproteases (MMP) are up-regulated in direct response to a hypoxic environment. MATERIALS AND METHODS: Colonic (SW1222), breast (MDA-MB231), and pancreatic (PSN-1) tumor cell lines were exposed to hypoxia (1% oxygen/94% nitrogen/5% carbon dioxide) for periods of up to 24 h. Reaction to a hypoxic environment was determined via invasion across a Matrigel-coated 8-microm Transwell filter. Activity of MMP 2 and 9 was assessed using gelatin zymography. Expression of tissue inhibitor of metalloproteases 1 (TIMP-1) was quantified using ELISA (Biotrak). Correlation between protease expression and invasive capacity was determined using a specific gelatinase inhibitor (MMPI; Calbiochem). RESULTS: All tumor lines demonstrated augmented invasion over 72 h (P < 0.01 all groups). Concomitant significant increase in MMP 2 and 9 activity was observed in the SW1222 and PSN-1 lines. MDA-MB231s showed increase in MMP 9 expression and in a unidentified 103-kDa gelatinase (P < 0.001). The hypoxia-augmented invasion was attenuated by the addition of a specific gelatinase inhibitor confirming interdependence. CONCLUSIONS: Hypoxia induces an increased invasive capacity via gelatinase up-regulation without loss of cell viability. This suggests a mechanism explaining the poorer prognosis seen in patients with protease-secreting solid adenocarcinomas.

Adenocarcinoma↗
PubMed2004

Tumour-expressed CD43 (sialophorin) mediates tumourmesothelial cell adhesion.

Mesothelial cell intercellular adhesion molecule-1 (ICAM-1) has recently been shown to play a role in tumour cell adherence to the peritoneum. However, solid tumours poorly express its most ubiquitous ligand, beta2 integrin. The aim of this study was to investigate the role of the beta2 integrin subunit and CD43, a known ligand for ICAM-1, in the development of peritoneal metastases. beta2 Integrin subunit and CD43 expression was assessed on a number of tumour cell lines. Adhesion of SW1222 and PSN-1 cells to human peritoneal mesothelial cells was investigated using a fluorometric assay incorporating an inhibitory antibody to beta2 integrin and CD43. beta2 Integrin expression was not inducible on these tumour cell lines, but Western blotting demonstrated CD43 expression in all the cancer cell lines examined and cell surface expression was confirmed by flow cytometry. The anti-CD43 antibody significantly reduced adhesion of PSN-1 and SW1222 cells to HPMC, however beta2 integrin inhibition did not reduce tumour cell adhesion. CD43 is expressed by a variety of carcinoma cell lines, and plays a role in tumour cell-peritoneal adhesion probably via interactions with its putative ligand ICAM-1.

Antigens, CD↗
PubMed2003

Laparoscopic-type environment enhances mesothelial cell fibrinolytic activity in vitro via a down-regulation of plasminogen activator inhibitor-1 activity.

BACKGROUND: Fewer intraperitoneal adhesions have been observed after laparoscopic surgery compared with conventional techniques. The aim of this study is to assess the effect of the pneumoperitoneum on mesothelial cell fibrinolytic activity by use of an in vitro model. METHODS: Human peritoneal mesothelial cells were seeded onto 24-well plates and incubated in carbon dioxide or helium at 5 mm Hg for 4 hours or standard culture conditions. Supernatant was removed for analysis at 0, 24, 48, and 72 hours after gas incubation and analyzed for plasminogen activator activity, total tissue plasminogen activator (tPA), and total plasminogen activator inhibitor-1 (PAI-1) concentrations by use of an enzyme-linked immunosorbent assay. The effect of different insufflation pressures (0, 7, and 14 mm Hg) was also examined. RESULTS: Enhanced plasminogen activator activity was observed at 48 hours and 72 hours from cells exposed to CO(2) (P<.04 each) and helium (P<.05 each) compared with control. This was associated with a decrease in PAI-1 concentrations at 48 and 72 hours in both the CO(2) and helium groups compared with control (P<.03 each, CO(2) vs control; and P<.04 each, helium vs control). No changes in tPA levels were observed. Changes in insufflation pressures did not affect plasminogen activator activity. CONCLUSIONS: These results suggest that incubation of human mesothelial cells with both CO(2) and helium in the absence of oxygen enhances mesothelial cell fibrinolytic activity because of a reduction in PAI-1 concentrations. These changes may participate in the observed reduction in adhesions after laparoscopic surgery relative to open surgery.

Carbon Dioxide↗
PubMed2002

Laboratory-based validation of a novel suture technique for wound closure.

Wound closure in open surgery is a fundamental skill acquired early during the surgeon's career. Individual modifications are adopted frequently by the more experienced surgeon in an effort to increase efficiency. To date, there has been no objective measurement regarding whether these modifications significantly impact economy of movement or procedure time. The advent of the Imperial College Surgical Assessment Device (ICSAD) allows standardized, objective evaluation of a novel suture technique for wound closure (study group) developed by one of the senior authors (DBH) and compares the technique to the current method taught by the Royal College of Surgeons of Great Britain and Ireland (control group). Ten surgical registrars underwent both tasks in a standardized manner for five repetitions. Mean total movements and duration of procedure were decreased significantly for the study group (analysis of variance: = 0.018 and = 0.033 respectively) with an economy index (total movements/total time) of 0.79 movements per second for the control group vs. 0.67 for the study group. This study demonstrates ICSAD's usefulness in defining a novel suture technique as a more efficient method of cutaneous closure than the currently advocated technique.

Dermatologic Surgical Procedures↗
PubMedDate not supplied

Hypoxia increases reepithelialization via an alphavbeta6-dependent pathway.

Reepithelialization is an essential step in successful cutaneous wound healing. Human keratinocytes, integral in this process, have been shown to have increased motility in the hypoxic healing edge of wounds correlating with the clinical success of semiocclusive hypoxic dressings, although the underlying mechanisms remain poorly understood. Subconfluent human keratinocyte cell monolayers were exposed to 1% hypoxia for up to 24 hours or control conditions. Re-oxygenation studies were performed up to 72 hours. Cellular alphav subunit and alphavbeta6 integrin expression was measured by flow cytometry. Migration scratch assays on fibronectin following hypoxic exposure were performed over 24 hours. Relative matrix metallo-proteinase (MMP)-2, 9 activity was determined by gelatin zymography with TIMP-1 levels assayed by enzyme-linked immunoassay. Sustained increases in alphav and alphavbeta6 expression were shown up to 48 hours in re-oxygenation studies (P < 0.001). Standardized scratch assays confirmed increased migration in the hypoxic group (P < 0.05). This effect was attenuated by the addition of a specific inhibitor of the alphavbeta6 integrin. MMP-2 and -9 activity was up-regulated following hypoxic exposure (P < 0.001; P < 0.05, respectively), whereas increased MMP expression was significantly retarded by addition of an alphavbeta6 inhibitor (P < 0.05). Migration on fibronectin was attenuated by a specific gelatinase inhibitor. We conclude that integrin alphavbeta6-dependent MMP-2 and -9 up-regulation is an important feature of increased migration in hypoxic human keratinocytes.

Antigens, Neoplasm↗
PubMedDate not supplied

ICAM-1 mediated tumor-mesothelial cell adhesion is modulated by IL-6 and TNF-alpha: a potential mechanism by which surgical trauma increases peritoneal metastases.

Peritoneal metastases frequently occur in different gastrointestinal cancers and have a poor prognosis. It is known that surgical injury promotes tumor growth and local recurrence rates and also the degree of surgical trauma correlated with the amount of tumor implantation into the peritoneum. The mechanism that mediates tumor cell adhesion to the mesothelium is not fully understood. This study investigates the role of ICAM-1, an important mediator of trans-mesothelial leucocyte migration, in tumor-mesothelial interactions as the initial step in the development of peritoneal recurrence using an in vitro model incorporating mesothelial cell monolayer derived from omental samples. We also investigate how the cytokines interleukins 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) modulate this process. We demonstrate that ICAM-1 blockade reduces the ability of both pancreatic and colonic cancer cell lines to adhere to the mesothelium. Preincubation of the mesothelial cell monolayer with either IL-6 or TNF-alpha enhances tumor cell adhesion, and this is associated with an increased expression of ICAM-1. Mesothelial CD44 expression, which has previously been implicated in this process, was unaffected by these cytokines. The use of an inhibitory monoclonal antibody against ICAM-1 attenuated the enhanced adhesion mediated by IL-6 or TNF-alpha. This study suggests that mesothelial ICAM-1 plays a role in the adhesion of tumor cells to the peritoneum in the development of peritoneal metastases.

Cell Adhesion↗