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Biomedical subjects

D Payne

Publications and source records attributed to D Payne.

At least 91 records · Page 5Linked to original sources
PubMed1998

Antithrombin and ischemia/reperfusion.

Acute inflammation, a localized response that occurs in various diseases, is characterized by neutrophil infiltration into tissues. This process requires neutrophils to initially tether and roll along the endothelium of postcapillary venules before undergoing firm adhesion and emigration out of the vasculature into the tissues. Recently, thrombin has been implicated at multiple sites in the inflammatory cascade, and may represent an important link between inflammation and thrombosis. Our recent studies demonstrate that thrombin is an important mediator of neutrophil-dependent injury in ischemia-reperfusion injury. Furthermore, antithrombin concentrate may be therapeutically efficacious in ischemia-reperfusion injury, as it is capable of attenuating the thrombin-mediated effects on neutrophil-endothelial interactions.

Animals↗
PubMed1998

[Current indications for exclusive radiotherapy].

The indications and limits of radiotherapy in the treatment of lung cancer are reviewed underlining the importance of different factors: the size of the tumours, the extension but also the treatment parameters (dose conformal, volume and technique). New perspectives are also seen: conformation radiotherapy and studies of changes in fractionation.

Dose Fractionation, Radiation↗
PubMed1997

Antithrombin III prevents and rapidly reverses leukocyte recruitment in ischemia/reperfusion.

BACKGROUND: P-selectin has recently been shown to be essential for leukocyte rolling after the reperfusion of ischemic mesentery. However, the mediators responsible for neutrophil rolling in ischemic microvessels remain entirely unclear. METHODS AND RESULTS: Intravital microscopy was used to examine leukocyte kinetics in a feline mesentery ischemia/reperfusion model. Sixty minutes of ischemia followed by reperfusion caused a profound increase in leukocyte rolling and adhesion. Pretreatment with the endogenous antithrombotic agent antithrombin III (ATIII) infused as a bolus (250 U/kg) reduced neutrophil rolling and adhesion to preischemic levels during reperfusion. No effect was seen with heat-inactive ATIII. Importantly, ATIII posttreatment also significantly reduced neutrophil rolling and adhesion during reperfusion, suggesting that ATIII can reverse the leukocyte recruitment response induced by ischemia/reperfusion. Vascular permeability was also reduced by 50% after ATIII administration. To determine whether ATIII could reverse thrombin-induced rolling directly, neutrophil rolling was performed on human endothelium in flow chambers. Indeed, thrombin-induced rolling, but not histamine-induced rolling, could be rapidly reversed with ATIII on endothelium, suggesting that ATIII affects thrombin rather than directly affecting neutrophils or the endothelium. CONCLUSIONS: This study demonstrates for the first time that thrombin plays an important role in ischemia-induced leukocyte rolling and adhesion and that ATIII can be used therapeutically postreperfusion to attenuate the leukocyte recruitment response in inflammation without the nonspecific effects associated with anti-adhesion molecule therapy.

Animals↗
PubMed1997

Enhanced control by radiotherapy of cervical lymph node metastases arising from nasopharyngeal carcinoma compared with nodal metastases from other head and neck squamous cell carcinomas.

PURPOSE: To test the hypothesis that metastatic cervical lymph nodes arising from nasopharyngeal carcinoma (NPC) are more readily controlled with radiotherapy than comparable nodes from squamous cell carcinomas of other head and neck sites (SCC). METHODS AND MATERIALS: One hundred four NPC patients with metastatic cervical nodes (mean size of the largest node equals 4.1 cm) were randomly selected from radiation treatment files for two time periods, 1969-1976 and 1983-1988, when radiation alone was the first line treatment. Candidate controls were selected randomly from radiation treatment files of node positive squamous cell carcinomas arising from the oropharynx, hypopharynx, oral cavity or larynx who were also treated by radical radiation therapy as sole initial treatment in the 1970s and 1980s. Each NPC case was matched with a control using the size of the largest involved node as the matching criterion. The median follow-up of all 208 patients was 3 years (4.2 years in NPC cases and 1.4 years in the matched controls). For those who were alive at last follow-up, the median follow-up for both arms was 7.7 years (6.7 years in NPC cases and 10.2 years in the matched controls). Nodal control was evaluated by clinical neck examination in both arms. Nodal recurrence was defined as relapse or persistence of metastatic nodal disease from day 1 of radiotherapy treatment. RESULTS: Despite a similar mean delivered dose to involved neck nodes (52.9 Gy for the NPC group and 53.9 Gy for the matched controls), the SCC group had significantly worse nodal control with radiation when compared to the NPC group (p < 0.0001, relative risk 3.0, 95% [1.8, 5.1]). The 3-year nodal recurrence-free rate among NPC cases was 71 +/- 5%, compared to 43 +/- 5% among matched controls. CONCLUSION: The result of this study supports the hypothesis that metastatic cervical nodes from NPC are more readily controlled by irradiation than cervical nodes of similar size arising from other head and neck squamous cell carcinomas. Further study is required to explore the reasons for this apparent radiosensitivity.

Adolescent↗
PubMed1997

Tumor necrosis factor-alpha induces leukocyte recruitment by different mechanisms in vivo and in vitro.

It is well established that E-selectin is the endothelial adhesion molecule that is primarily responsible for mediating leukocyte rolling on TNF-alpha-stimulated cultured endothelial cells. Despite this, few studies in in vivo inflammatory models have observed reduced leukocyte accumulation using mAbs against E-selectin. The objective of this study was to compare the function of E-selectin on endothelial cells in vitro with its role in TNF-alpha-induced leukocyte recruitment in vivo using EL246, a mAb that blocks the function of E-selectin on activated feline endothelial cells. In vitro experiments using feline endothelial cells showed that EL246 functionally inhibits E-selectin-dependent leukocyte recruitment induced by TNF-alpha, without affecting the function of other rolling mechanisms. Intravital microscopy of single 25- to 40-microm venules in the feline mesentery was then used to examine leukocyte rolling and adhesion in response to superfusion with TNF-alpha. TNF-alpha treatment significantly increased the number of both rolling and adherent leukocytes and significantly decreased leukocyte rolling velocity. Treatment with EL246 (1 mg/kg), either i.v. at the start of the TNF-alpha protocol or directly into the superior mesenteric artery after 3 h of TNF-alpha treatment, had no effect on leukocyte rolling, adhesion, or rolling velocity. However, treatment with the selectin-binding carbohydrate, fucoidan, reduced leukocyte rolling to below baseline levels. These results suggest that in contrast to its prominent role on cultured endothelial cells, E-selectin does not contribute to leukocyte recruitment in TNF-alpha-stimulated feline mesenteric venules in vivo.

Animals↗
PubMed1997

Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography.

In this study, we have used time-lapse video cinematography to study fertilization in 50 human oocytes that had undergone intracytoplasmic sperm injection (ICSI). Time-lapse recording commenced shortly after ICSI and proceeded for 17-20 h. Oocytes were cultured in an environmental chamber which was maintained under standard culture conditions. Overall, 38 oocytes (76%) were fertilized normally, and the fertilization rate and embryo quality were not significantly different from 487 sibling oocytes cultured in a conventional incubator. Normal fertilization followed a defined course of events, although the timing of these events varied markedly between oocytes. In 35 of the 38 fertilized oocytes (92%), there were circular waves of granulation within the ooplasm which had a periodicity of 20-53 min. The sperm head decondensed during this granulation phase. The second polar body was then extruded, and this was followed by the central formation of the male pronucleus. The female pronucleus formed in the cytoplasm adjacent to the second polar body at the same time as, or slightly after, the male pronucleus, and was subsequently drawn towards the male pronucleus until the two abutted. Both pronuclei then increased in size, the nucleoli moved around within the pronuclei and some nucleoli coalesced. During pronuclear growth, the organelles contracted from the cortex towards the centre of the oocyte, leaving a clear cortical zone. The oocyte decreased in diameter from 112 to 106 microm (P < 0.0001) during the course of the observation period. The female pronucleus was significantly smaller in diameter than the male pronucleus (24.1 and 22.4 microm respectively, P = 0.008) and contained fewer nucleoli (4.2 and 7.0 respectively, P < 0.0001). After time-lapse recording, oocytes were cultured for 48 h prior to embryo transfer or cryopreservation. Embryo quality was related to fertilization events and periodicity of the cytoplasmic wave, and it was found that good quality embryos arose from oocytes that had more uniform timing from injection to pronuclear abuttal and tended to have a longer cytoplasmic wave. In conclusion, we have shown that time-lapse video cinematography is an excellent tool for studying fertilization and early embryo development, and have demonstrated that human fertilization comprises numerous complex dynamic events.

Cell Nucleus↗
PubMed1997

Reduced pregnancy rates following the transfer of human embryos frozen or thawed in culture media supplemented with normal serum albumin.

Over a 26 month period 17% of couples having treatment in our clinical programmes selected a commercially available protein (normal serum albumin, NSA) prepared from pooled human sera instead of using their own serum as a supplement for their embryo culture media. In a retrospective analysis of >2000 gonadotrophin-stimulated cycles and 1000 cycles where frozen/thawed embryos were transferred, fertilization, embryo quality and pregnancy rates following in-vitro fertilization (IVF), gamete intra-Fallopian transfer (GIFT) or intracytoplasmic sperm injection (ICSI) were unaffected by the type of protein used to supplement the culture medium. When embryos were thawed in medium containing NSA, both pregnancy (PR) and implantation rates (IR) were significantly lower (P <0.05) than if the medium was supplemented with serum (PR 8.3% and 17.5%; IR 4.6% and 10.5%). Inclusion of NSA before freezing reduced the IR of thawed embryos. To further test this observation all cycles where embryos were cultured and frozen in medium containing NSA (173 cycles) were matched to cycles where serum was used and the outcome was compared. At the end of 1995 just over half of the embryos in both groups had been thawed. No statistical difference was noted in the pregnancy rates (NSA, 5.6% versus serum, 11.3%) but the IR per embryo was significantly lower when embryos were cultured and frozen in medium supplemented with NSA (2.2%) than when serum was used as the supplement (6.6%).

Blood↗
PubMed1997

Analysis of unfertilized oocytes subjected to intracytoplasmic sperm injection using two rounds of fluorescence in-situ hybridization and probes to five chromosomes.

Chromosomal aberrations are the major cause of pre- and post-implantation embryo wastage and some studies suggest that half of all human conception have a chromosomal abnormality. Analysis of gametes provides information on the origin of these chromosomal aberrations. The purpose of this study was to develop a reliable multi-probe fluorescence in-situ hybridization (FISH) procedure that would enable us to investigate aneuploidy in unfertilized oocytes subjected to intracytoplasmic sperm injection (ICSI). Oocytes were spread with HCl and Tween 20 solution, and then two rounds of triple-probe FISH were performed on each oocyte using directly-labelled centromeric probes: chromosomes 1, 7, 15 (overnight hybridization); chromosomes 1, X, Y (2 h hybridization). After the first round, the slides were counterstained and evaluated, and the positions of FISH signals were recorded. For the second round, the counterstain was removed and the second probe cocktail was applied. The chromosome 1 probe was an internal control for the two hybridization procedures, while the Y chromosome probe was used to detect sperm DNA. To evaluate the method, a total of 79 oocytes from 27 patients were studied. Of these, 67 (84.8%) were successfully spread and 97% of these oocytes exhibited discernible FISH signals. Upon lysis, oocytes exhibited one or more DNA fragments (mean 1.9, range 1-3). Of the 65 analysable oocytes, 17 (26.2%) displayed a normal haploid chromosome constitution with paired spots for the two chromatids. A further 23 oocytes (35.4%) showed an ambiguous chromosome complement due to an abnormal number of DNA fragments which may have resulted from loss of DNA during spreading or to an abnormal oocyte, while 25 oocytes (38.4%) displayed aneuploidy for one or more of the chromosomes studied. In conclusion, this new approach is a quick and efficient method with which numerical chromosomal abnormalities in human oocytes can be studied; interpretation of the patterns of DNA fragments and FISH signals requires further clarification.

Aneuploidy↗
PubMed1997

Explaining brain death: a critical feature of the donation process.

To examine how a family's understanding of brain death may affect the decision to donate, an interview study was conducted with the immediate next of kin of 164 medically suitable organ donor candidates. Telephone interviews were conducted with members of both donor and nondonor families 4 to 6 months after the relative's death. Only 61% of the donor and 53% of the nondonor respondents said they had received an explanation of brain death. Few respondents reported that the hospital or organ procurement organization staff used visual aids to clarify or reinforce the information they were given. Next of kin who decided against donation had far less understanding of brain death than did those who decided in favor of it. Before making an organ donation request, healthcare providers must inquire about and address common misunderstandings people have about brain death. Healthcare teams should develop and be trained on a clear protocol for communicating with the families of patients who may be potential organ donors.

Adolescent↗
PubMed1997

Successful treatment of a generalized human papillomavirus infection with granulocyte-macrophage colony-stimulating factor and interferon gamma immunotherapy in a patient with a primary immunodeficiency and cyclic neutropenia.

BACKGROUND: We describe a patient with generalized verrucosis secondary to human papillomavirus (HPV) type 2 infection and a primary immunodeficiency and cyclic neutropenia. Treatment, which was well tolerated, included granulocyte-macrophage colony-stimulating factor and interferon gamma (IFN-gamma). In vitro assays to assess responses of T lymphocytes to mitogens (ie, proliferation assay and IFN-gamma enzyme-linked immunosorbent assay) were performed. In situ hybridization and polymerase chain reaction were used to detect HPV DNA in skin biopsy specimens. OBSERVATIONS: The T lymphocytes of the patient showed a significant (P < .05, unpaired Student t test) defect in IFN-gamma production (the basis for initiating IFN-gamma therapy). The response to immunotherapy was confirmed by using molecular methods. Six months after the completion of immunotherapy, HPV DNA was undetectable in skin samples from clinically regressed warts (according to the results of in situ hybridization and polymerase chain reaction). CONCLUSIONS: Our patient had treatment-resistant generalized verrucosis for 13 years. Treatment with granulocyte-macrophage colony-stimulating factor and IFN-gamma may have reconstituted an immune response against HPV, resulting in the dramatic regression of her widespread warts.

Adolescent↗
PubMed1997

Cutaneous squamous cell carcinoma in human immunodeficiency virus-infected patients. A study of epidemiologic risk factors, human papillomavirus, and p53 expression.

OBJECTIVE: To examine risk factors for the development of cutaneous squamous cell carcinoma (SCC) in a group of human immunodeficiency virus (HIV)-infected patients, including evaluation and detection of epidemiologic risk factors of human papillomavirus (HPV) and p53 expression. DESIGN: Case-control study during a 3-year period. SETTING: Dermatologic referral center. PATIENTS: Thirty-three HIV-infected patients who had 97 SCCs were compared with 24 HIV-infected patients who had 70 basal cell carcinomas (BCCs). MAIN OUTCOME MEASURES: Age, skin type, amount of sun exposure, actinic damage, family history of skin cancer and history of smoking and warts. Specimens of SCC and BCC were examined for HPV using polymerase chain reaction. Presence of p53 was examined using immunohistochemical analysis. Specimens from tumor-free, non-sun-exposed areas from these same patients were used as controls. RESULTS: Risk factors for the development of both types of carcinoma included fair skin type and excessive sun exposure (> 6 h/d during the previous 10 years). The HIV-infected patients with SCCs tended to have outdoor occupations. The location of SCCs favored the head and neck; BCCs were located on the trunk. Patients with SCCs had later-stage HIV disease than did patients with BCCs. Half of the patients with SCC had a history of genital or nongenital warts. Seventy-one percent (17/24) had a smoking history. No statistical difference existed between patients with SCCs and BCCs for history of smoking or warts. Human papillomavirus was not found in most of our SCC, BCC, or control specimens. However, 92% (22/24) of the SCC specimens and 90% (18/20) of the BCC specimens stained for p53. Control specimens from non-sun-exposed skin of HIV-infected patients did not stain for p53. Epidermal staining was present in 95% (17/20) of tissue adjacent to SCCs and 47% (7/15) of tissue adjacent to BCCs. A significantly positive correlation existed between the amount of sun exposure and the amount of p53 staining seen in adjacent epidermal tissue (r = 0.07; P = .01). CONCLUSIONS: Risk factors for the development of SCCs and BCCs in HIV-infected patients are similar: fair skin type and excessive sun exposure. Our study does not support that HPV is an oncogenic factor in the development of these cutaneous tumors but provides evidence that p53 overexpression may play a role.

Adult↗