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Biomedical subjects

R M Taylor

Publications and source records attributed to R M Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1992

A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor.

BACKGROUND: Blood vessel growth is necessary for normal tissue homeostatis and contributes to solid tumor growth. Methods to quantitate neovascularization should be useful in testing biological factors and drugs that regulate angiogenesis or to induce a vascular supply to promote wound healing. EXPERIMENTAL DESIGN: An extract of basement membrane proteins (Matrigel) was found to reconstitute into a gel when injected subcutaneously into C57/BL mice and to support an intense vascular response when supplemented with angiogenic factors. RESULTS: New vessels and von Willebrand factor antigen staining were apparent in the gel 2-3 days after injection, reaching a maximum after 3-5 days. Hemoglobin content of the gels was found to parallel the increase in vessels in the gel allowing ready quantitation. Angiogenesis was obtained with both acidic and basic fibroblast growth factors and was enhanced by heparin. Several substances were tested for angiostatic activity in this assay by coinjection in Matrigel with fibroblast growth factor and heparin. Platelet-derived growth factor BB, interleukin 1-beta, interleukin-6, and transforming growth factor-beta were potent inhibitors of neovascularization induced by fibroblast growth factor. Tumor necrosis factor-alpha did not alter the response but was alone a potent inducer of neovascularization when coinjected with Matrigel and heparin. Consistent with the previously demonstrated importance of collagenase in mediating endothelial cell invasion, a tissue inhibitor of metalloproteinases that also inhibits collagenases was found to be a potent inhibitor of fibroblast growth factor-induced angiogenesis. CONCLUSIONS: Our assay allows the ready quantitative assessment of angiogenic and anti-angiogenic factors and should be useful in the isolation of endothelial cells from the capillaries that penetrate into the gel.

Angiogenesis Inducing Agents↗
PubMed1991

Availability of transplantable organs from brain stem dead donors in intensive care units.

OBJECTIVE: By audit from January to June 1989 to quantify, separately for hearts, kidneys, liver, lungs and corneas, the possible increases in transplantable organs from brain stem dead potential donors in intensive care units and to compare them with the increases achieved in October-November 1989, during intense, national publicity about transplantation. DESIGN: Prospective audit of all deaths in intensive care units in England from 1 January to 30 June 1989 and subsequent case study of the impact of publicity on offers and donations during October-November 1989. SETTING: 15 regional and special health authorities in England. PATIENTS: 5803 patients dying in intensive care units, of whom 497 were confirmed as brain stem dead and had no general medical contraindication to organ donation. MAIN OUTCOME MEASURES: Organ specific suitability for transplantation (as reported by intensive care units); consent for donation of specific suitable organs; and procurement of specific organs reported as suitable for transplantation and offered. RESULTS: In the 497 (8.6%) brain stem dead potential donors were estimated the organ specific suitability for heart as 63%, kidneys 95%, liver 70%, lungs 29%, and corneas 91%. Refusal of relatives (30%) accounted for major losses of suitable organs of all types. For kidneys the loss was equivalent to 44% of brain stem dead actual kidney donors. No discussion of organ donation was the second most important reason for missed kidney donors, the loss being equivalent to 10% of brain stem dead actual donors. Non-procurement or difficulties with allocating organs was the second most notable cause of missed suitable liver and lung donors; 29% (55) of the offered total of 189 liver donors and 27% (21) of 78 offered suitable lung donors in six months. Non-procurement of suitable, offered organs was rare for kidneys and modest, of the order of 13% and 10% respectively, for heart and corneas. Corneal donation from brain stem dead potential donors might be improved nearly as much (that is, a 78% increase in brain stem dead actual corneal donors) by specific measures to promote corneal donation when other organs are offered as by reducing the overall refusal rate. Restricted offers, non-procurement, and no discussion of donation accounted for nearly equal numbers of lost donations of hearts (each equivalent to 15% of donated hearts). During October-November 1989 when there was intense, positive publicity about transplantation the rates of refusal and non-discussion fell compared with during January-June (22%, 36/163 v 30%, 138/460; 7%, 33/497 v 2%, 4/167 respectively). Offers of suitable donors increased significantly (p less than 0.02) compared with the first six months of 1989, most notably for heart donors (80 v 60.1 expected) and kidney donors (122 v 102.1 expected) but only for kidneys was there a noticeable 17% increase in actual donors (118 actual audited donors v 100.8 expected donors; p = 0.09). CONCLUSIONS: Four strategies to increase the supply of transplantable organs from brain stem dead potential donors in intensive care units were identified: (a) reducing refusal of relatives (b) avoiding non-procurement of actually suitable organs (by logistical initiatives) and deterioration of initially suitable organs (by donor care initiatives); (c) converting restricted offers to unrestricted offers; and (d) ensuring discussion with families. Early referral to the transplant team or coordinator gives time for discussion about donor care and agreement on medical suitability for donation of specific organs. Solving some of the logistical problems of non-procurement may be a prerequisite for increased offers to be translated into increased donations. The impact of publicity therefore needs to be measured on offers of suitable donors as well as by actual donations.

Brain Death↗
PubMed1991

Renal epithelium: reversal of cytotoxic damage by addition of anti-thymocyte globulin.

A novel in vitro assay of renal epithelium tight junction function was used to assess the efficacy with which rabbit anti-thymocyte globulin (ATG) blocks epithelium damage mediated by lymphokine-activated killer (LAK) cells. It was found that LAK cells lysed renal epithelial cells poorly in standard chromium-release assays but that they caused a rapid, and almost total, reduction in trans-epithelium monolayer resistance, indicating tight junction failure and, hence, loss of tissue function. LAK cell-mediated cytolysis of the sensitive K562 cell line was completely blocked in the presence of ATG at a concentration of 200 micrograms/ml. Addition of ATG at this concentration to damaged renal cell monolayers in the presence of LAK cells allowed the trans-monolayer resistance to recover rapidly to levels approaching the values recorded before initial addition of LAK cells. On this basis it seems likely that the rapid restoration of renal function frequently observed after appropriate "rescue" therapy during episodes of acute rejection may reflect subtle changes in tissue function rather than recovery from widespread graft cell cytolysis.

Animals↗
PubMed1991

Management of duodenal injuries by proximal T-tube drainage.

Duodenal injuries may be caused by blunt or penetrating trauma. There is a high mortality rate with this type of injury, particularly when associated with pancreatic trauma. The surgical management of such injuries is difficult and a technique is described which may reduce postoperative morbidity, as illustrated by the two cases described.

Accidents, Traffic↗
PubMed1991

Monoclonal and polyclonal antibodies: clinical aspects.

Over the years, the ways in which the antibodies ATG and OKT3 have been used in clinical transplantation have changed. ATG was first on the scene and has been used as initial immune suppression in certain forms of transplantation, of which cardiac transplantation is one good example. It has not been commonly used in renal transplantation, but there is evidence that this may be changing. The nephrotoxic side-effects of cyclosporin continue to cause anxiety, and high rates of initial non-function of kidney allografts have made early management difficult; this may have contributed to some early graft failures. There is currently interest in avoiding the use of cyclosporin initially by commencing immune suppression treatment with ATG, in an attempt to improve the immediate function rate of kidney grafts. When function is established, more conventional treatment schedules, usually with cyclosporin A, are introduced. ATG is also being incorporated in basic immunesuppressive regimes as part of multiple drug treatments. The hypothesis of multiple drug treatments is based on the idea that if a number of different immune suppressive agents are used, then the dose of each may be reduced, with minimisation of side-effects. This concept may be true, but the price may be that of an increased rate of malignancy in the long-term graft recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Antilymphocyte Serum↗
PubMed1991

Neuroleptic malignant syndrome: occurrence in a child after reconstructive surgery.

The occurrence of the rare but potentially fatal neuroleptic malignant syndrome must be considered by the surgeon treating a patient who develops hyperthermia, mental abnormalities, autonomic instability, and muscle rigidity after exposure to phenothiazines or other neuroleptic drugs. The dopamine agonist bromocriptine appears to be the treatment of choice in adults and seemed to be effective and well tolerated in our patient. Although the syndrome cannot be prevented, recognition is crucial, since effective general and specific therapy is available. Differentiating neuroleptic malignant syndrome from malignant hyperthermia allows early appropriate treatment with bromocriptine.

Child↗
PubMed1991

Transfusion-induced immunosuppression and red cell clearance.

While blood transfusion is increasingly implicated in the aetiology of tumour recurrence, the mechanism of this effect is unclear. Cancer-bearing patients are known to have factors in their sera which depress the function of normal lymphocytes. It is possible that blood transfusion accentuates this natural suppression. An animal model was therefore developed to study the effect of blood transfusion on humoral immunosuppressive activity and its possible relationship to red cell clearance. WAG rats given a transfusion of chromium-labelled allogeneic but blood-group compatible DA rat blood, developed significantly increased (P < 0.001) levels of lymphocyte suppressive factors in plasma (maximum at 7 days) which coincided with accelerated red cell clearance (t1/2 = 7 days). A transfusion of syngeneic WAG blood caused only a small transient increase in plasma suppression and red cells were cleared at a normal rate (t1/2 = 13 days) consistent with previous studies. However, when syngeneic WAG red cells were lysed and the red cell membranes infused there was a rapid increase in plasma suppression (P < 0.001), similar to but less prolonged than that achieved with allogeneic blood. The immunosuppressive effect of blood transfusion may result from accelerated clearance of allogeneic or damaged syngeneic red blood cells.

Animals↗
PubMed1991

Renal allograft rejection: investigation of alloantigen presentation by cultured human renal epithelial cells.

Defined lines of primary human renal epithelial cells were established and their expression of class II major histocompatibility (MHC) antigens was up-regulated by culture with interferon-gamma (IFN-gamma). The ability of these cells to stimulate the proliferation of allogeneic peripheral blood mononuclear cells (PBMC) was compared with that of endothelial cells and splenic mononuclear cells. It was found that both endothelial and splenic cells stimulated lympho-proliferation but that cultured renal epithelial cells were non-stimulatory. The failure of proliferation by allogeneic lymphocytes in culture with epithelial cells was not overcome by treatment with interleukin-1 (IL-1) or indomethacin. However, addition of IL-2 to mixed cultures of allogeneic PBMC and renal epithelial cells stimulated lympho-proliferation and allowed the generation of lymphoid cell lines which mediated non-specific lysis of renal epithelial cell lines. Stimulation of PBMC by mixed lymphocyte culture yielded an allospecific T-cell line which was added either to renal epithelial cells from the same donor as the stimulator cells used in the priming reaction or from a third-party donor; lympho-proliferation was observed in the specific secondary reaction but not in the non-specific reaction. These findings indicate that class II MHC antigen-expressing epithelial cells within a renal allograft may not initially stimulate the proliferation of resting allospecific recipient lymphocytes. However, within a rejecting graft it is likely that high local concentrations of IL-2 are present and that many of the infiltrating allospecific lymphocytes will be primed by previous contact with donor antigen-presenting cells, such as vascular endothelial cells or dendritic cells. Therefore, expression of class II MHC antigens by epithelial cells within the microenvironment of a renal allograft may render such cells immunogenic and able to play a direct role in the lymphocyte-mediated intragraft rejection process.

Antigen-Presenting Cells↗
PubMed1991

Renal allograft rejection. Functional impairment of kidney epithelial cell monolayers mediated by lymphokine-activated killer cells and by antibody.

A continuous line of human kidney epithelial cells was cultured to confluency on porous membranes, and the formation of intercellular tight junctions was monitored by measuring increases in the trans-monolayer electrical resistance. Typical monolayers developed functioning tight junctions within 4 days of culture and showed an increase in resistance of 1840 +/- 440 ohms (mean +/- SD; n = 5) at this time. Conventional 51Cr release assays showed that suspended kidney cells were lysed by specific antibody and complement but were relatively resistant to lysis mediated by lymphokine-activated killer cells. However, when antibody and complement or LAK cells were added to functioning kidney cell monolayers the electrical resistance of the monolayers was rapidly reduced in both cases. In the absence of trans-monolayer resistance the ion gradients essential for renal tubular function will not be supported. These results indicate that the ability of a cytotoxic effector cell to liberate 51Cr from suspended kidney cells may not be a sensitive assay for the ability of these effector cells to impair the function of structured kidney cell monolayers. It is possible that significant kidney dysfunction may occur during renal allograft rejection by failure of trans-epithelium resistance in the absence of widespread epithelial cell lysis.

Animals↗
PubMed1991

Alterations in circulating lymphocyte number and function after circulation through colorectal carcinomas.

Thirty-six patients undergoing curative resection for colorectal cancer were studied to determine the effect of the tumor on lymphocytes circulating through it. In the venous blood draining the tumor, there was an increased percentage of natural killer (NK) cells (p = 0.001), no difference in overall NK cell function, and decreased T-lymphocyte activation (p = 0.035) and proliferation (p = 0.002) compared with the lymphocytes in the arterial blood supplying the tumor. There were no significant differences in the control group of 16 patients. Local effects of colorectal cancer may include the ability to down-regulate T and NK cell function while increasing the number of NK cells. Means of enhancing antitumor activity therapeutically in an adjuvant setting, possibly through the portal vein during surgery, need to be considered, especially in the light of the immunosuppressive effects of surgery.

Aged↗
PubMed1990

Renal replacement treatment for diabetic patients in Newcastle upon Tyne and the Northern region, 1964-88.

OBJECTIVES: To review the experience of renal replacement treatment in diabetic patients treated in Newcastle upon Tyne and the Northern region from 1964 to 1988, and to compare the morbidity and mortality of diabetic patients treated with dialysis or transplantation with those of matched controls of non-diabetic patients. DESIGN: Retrospective study of clinical case notes. SETTING: Renal units of the Northern region, particularly that in Newcastle upon Tyne. PATIENTS: All 65 diabetic patients treated by renal replacement treatment in Newcastle upon Tyne from 1964 to 1987; 42 diabetic patients were matched with 42 non-diabetic patients according to age, sex, year of starting treatment, and type of treatment (dialysis or transplantation). MAIN OUTCOME MEASURES: Sex, age, renal biopsy findings, blood pressure, history of diabetic treatment, and plasma creatinine concentration at the start of renal replacement treatment. History of renal replacement treatments, suitability for transplantation, history of transplantation, cumulative survival, and cause of death during follow up. Survival of technique, cumulative survival of the first peritoneal catheter and history of peritonitis in patients treated with continuous ambulatory peritoneal dialysis; source of graft, histocompatibility antigens, duration of associated stay in hospital, and graft survival in patients receiving renal or pancreatic transplant. RESULTS: 1259 Patients with chronic renal failure were accepted for renal replacement treatment in Newcastle upon Tyne, of whom 65 (5%) had diabetes. The first was accepted in 1974, and between 1974 and 1980 another 15 were treated (mean age 42 years; 4% of new patients). From 1981 to 1987, 49 diabetic patients (mean age 44; 9% of new patients) were treated. Fifty patients (77%) had insulin dependent diabetes and the remaining 15 (23%) non-insulin dependent diabetes. On average, the patients were aged 25 (range 5-57) when diabetes was first diagnosed and 44 (range 24-70) at the start of renal replacement treatment. The mean age at the start of treatment was 40 for patients with non-insulin dependent diabetes and 58 for patients with non-insulin dependent diabetes. Transplantation was performed in 33 of the diabetic patients, whose mean age was lower than that of those who did not receive a transplant (41 v 48 respectively, p less than 0.05). Comparison between the 42 diabetic patients and matched controls showed that the overall survival at five years was 46% and 77% respectively. The three year survival of the diabetic patients who did not receive a transplant was poor (41% v 79% respectively). Of patients transplanted, survival at five years was 73% in the diabetic patients and 90% in the controls. However, there was no significant difference in the five year graft survival (64% v 46% respectively). CONCLUSIONS: Diabetes adversely affects morbidity and mortality in patients having renal replacement treatment, but renal transplantation seems to be the best option for treating diabetic patients with end stage renal failure.

Adolescent↗