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Biomedical subjects

G Proud

Publications and source records attributed to G Proud.

At least 73 records · Page 4Linked to original sources
PubMed1989

I spy efficiency.

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Ambulatory Care Facilities↗
PubMed1989

Reducing renal injury during transplantation.

Damage sustained by an ischaemic kidney is reduced by cooling the organ. For this reason kidneys are rapidly cooled during the retrieval operation and preserved at low temperature before implantation. When the kidney is removed from cold storage for implantation into the recipient it gradually rewarms (second warm ischaemic time) and a prolonged second warm ischaemic time has been shown to be a cause of acute tubular necrosis following transplantation. The temperature rise in a kidney during implantation has been poorly investigated and little work to minimize that rise has been carried out. This study investigates, in an animal model, the changes that occur in the core temperature of kidneys during the second warm ischaemic time. A jacket has been designed which greatly reduces the rate of kidney rewarming during simulated operative conditions. Kidneys unprotected by the test system showed a rapid rise in temperature from a mean of 1 degrees C to a mean of 20 degrees C after 45 min, compared with those kidneys placed in the protective jacket in which the temperature rose to a mean of only 8 degrees C in the same time. The jacket is not bulky and is simple to use. Maintaining a low kidney core temperature during the second warm ischaemic time will reduce injury to the kidney and should be part of routine clinical practice.

Anastomosis, Surgical↗
PubMed1989

In vitro study of human skeletal muscle strips: effect of nonesterified fatty acid supply on glucose storage.

To examine the effect of increased nonesterified fatty acid concentration on glucose storage in human muscle, an in vitro method for study of glycogen synthesis in this tissue has been established. Muscle strips obtained from rectus abdominus during elective abdominal surgery were clamped at resting length, and adenosine triphosphate/total adenosine nucleotide ratios remained constant for 3 hours ex vivo. Leakage of enzyme markers of muscle damage was minimal, and electron microscopy showed preserved myofibril ultrastructure. Insulin stimulation brought about a dose-dependent increase in rates of glycogen synthesis with a half-maximal effect at 9 x 10(-10) mol/L insulin. In 15 consecutive studies, basal rates of glycogen synthesis were 4.1 +/- 0.5, 3.2 +/- 0.7, and 3.0 +/- 0.3 nmol glucose/25 mg/h in the absence of palmitate, with 1.4 mmol/L and 2.8 mmol/L palmitate, respectively. Insulin-stimulated rates of glycogen synthesis were 8.6 +/- 1.2, 6.0 +/- 1.8, and 5.8 +/- 0.8 nmol glucose/25 mg/h. Thus, increasing fatty acid concentrations decreased rates of glycogen synthesis both basally and with insulin stimulation. The insulin signal itself was not affected as the percentage stimulation over basal rates remained approximately constant in the presence or absence of fatty acid (2.1-, 1.9- and 1.9-fold, respectively). Insulin sensitivity in vivo is usually expressed as absolute rates of glucose uptake during euglycemic hyperinsulinemia, and if plasma fatty acid elevation were to be studied in vivo an erroneous conclusion may be reached of resistance to hormone action per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The relevance of a more sensitive crossmatch assay to renal transplantation.

While the importance of the standard preoperative crossmatch in predicting renal graft success is accepted, a more rapid and sensitive assay may be of additional clinical benefit. We have developed a flow cytometric assay to detect the presence of antibodies (IgG) in the recipient sera directed against donor lymphocytes, prior to transplantation. This assay is more rapid and sensitive than the conventional cytotoxic test. In a clinical study the sera of 75 renal graft recipients were tested, all of which were negative in their conventional crossmatch; 12 of these were identified as having T cell-directed IgG, and 4 had B cell antibody. Graft failure was not significantly different in the positive and negative antibody groups, as defined by flow cytometry (P = 0.147, chi square test). The incidence of postoperative complications was studied in the 60 grafts functioning at three months. Recipients with donor B or T cell directed antibodies had a longer primary nonfunction (P = 0.0098, Mann-Whitney U test), and showed a higher number of rejection episodes (P = 0.014, Mann-Whitney U test); accordingly they were more likely to require strong immunosuppressive agents such as OKT3 or ATG (P less than 0.05, chi square test). Patients with donor-directed antibodies were also hospitalised for a longer period (P = 0.015, Mann-Whitney U test) and had a higher creatinine level 3 months after transplantation (P = 0.021 Mann-Whitney U test). This study shows that the described preoperative flow cytometric crossmatch is capable of defining a population of renal transplants who form an at-risk group. Thus this assay has considerable potential in pretransplant matching of recipients with a particular graft donor.

Antibodies↗
PubMed1989

Renal allograft rejection: protection of renal tubular epithelial cells from lymphokine activated killer cell mediated lysis by pretreatment with cytokines.

Human renal tissue was disaggregated by passage through a stainless-steel mesh and the resultant material was separated on the basis of particle size. The tubular fraction recovered from a 45 microns mesh was cultured and after a period of between 5 and 7 days outgrowing adherent epithelial cells were identified. All of these cells contained cytokeratin and after culture for at least 14 days fewer than 5% showed surface HLA-DR antigens. Cultured renal epithelial cells were rapidly lysed by lymphokine activated killer (LAK) cells which were produced from peripheral blood lymphocytes of normal subjects by incubation for 5 days in the presence of either recombinant interleukin-2 (IL-2) or mixed lymphocyte reaction (MLR) supernatant. Stimulation of the cultured epithelial cells for 5 days with either gamma-interferon or MLR supernatant resulted in 67% +/- 9% (mean +/- SD; n = 8) of the cells showing an upregulation of HLA-DR expression. These treated cells were markedly less sensitive to lysis by LAK cells than the untreated cells. Thus, if renal cell damaging LAK cells are generated from lymphocytes in vivo by the action of IL-2 produced during rejection, then gamma-interferon, which is also produced during rejection, may partially protect the renal cells from such LAK cell mediated damage.

Biological Factors↗
PubMed1989

Renal allograft rejection: possible involvement of lymphokine-activated killer cells.

Human renal allograft tissue was recovered at transplant nephrectomy from three patients with irreversible loss of graft function. This tissue was disaggregated and separated into two fractions on the basis of particle size. Fraction 1 contained glomeruli and developed a mixed outgrowth containing adherent epithelial and mesangial cells after a limited period of culture. Fraction 2 contained fragments of renal tubules and produced monolayers of tubular epithelial cells during culture. A population of lymphoid cells was observed to grow from the primary disaggregate into medium supplemented with recombinant human interleukin-2 (IL-2). After culture for 5 days these lymphoid cells were predominantly CD3-positive and carried both class II major histocompatibility antigens (MHC) and the CD25 IL-2 receptor. Culture of peripheral blood-derived mononuclear cells with IL-2 caused the generation of lymphokine-activated killer (LAK) cells; these cells were able to lyse both glomerular and tubular cells grown from nephrectomy tissue without showing MHC antigen restriction. The lymphoid cells grown from renal allograft tissue showed a similar lytic potential for both renal cells prepared from the same nephrectomy specimen and from third party renal tissue. It is possible that any LAK cells formed within a renal allograft by the action of IL-2 may contribute to the tissue destruction observed during graft rejection.

Cells, Cultured↗
PubMed1988

Rapid detection of low levels of donor specific IgG by flow cytometry with single and dual colour fluorescence in renal transplantation.

Lymphocytotoxic immunoglobulin is routinely assayed before human renal transplantation. If IgG directed against donor T cells is detected in the serum of the potential recipient, transplantation is not performed as it is associated with a poor graft outcome. Poor sensitivity of the conventional assay has been postulated as being the cause of some graft failures. Two new flow cytometric assays are described which are more sensitive than the conventional test. The first assay requires manual separation of T and B lymphocytes and therefore takes a similar time to perform as the conventional assay. The second assay utilises a two-colour system and lymphocyte's separation is by fluorescence. This assay takes half the time to perform, thereby decreasing graft ischaemic time before transplantation.

Dose-Response Relationship, Immunologic↗
PubMed1988

Renal transplantation: the non-starters.

Renal transplants do not always function immediately and this non-function may be related to poor long-term graft survival. The causes of this primary non-function (PNF) are poorly understood. The incidence of PNF in 106 consecutive renal transplants was found to be 57 per cent. Using stepwise logistic regression analysis of 20 prospectively collected variables for each transplant two have been found to be positively associated with PNF of the transplant: (1) the use of cyclosporin as an immunosuppressant and (2) a second warm ischaemia (anastomosis) time of more than 30 min. It is proposed that the use of cyclosporin be restricted in the early post-transplant period until initial function of the transplant is established. The surgical procedure of kidney transplantation should be planned to minimize the anastomosis time prior to recirculation of the graft.

Cyclosporins↗
PubMed1988

Transcutaneous oxygen monitoring as an indication of prognosis in critical ischaemia of the lower limb.

Critical ischaemia in the chronically ischaemic limb has proved difficult to define both in clinical and objective terms. This has meant that assessment of patients has in the past relied heavily on the angiographic appearances of the vessels which is also an unreliable technique. Attempts have been made to define critical ischaemia objectively in terms of the ankle systolic pressure but recent studies have shown that although the definition produced in 1982 was highly specific, the sensitivity was low with many patients with the clinical features of critical ischaemia having ankle pressures which were higher than the recommended values. Recently the transcutaneous measurement of oxygen tension has been used to assess patients with peripheral vascular disease and has proved of use in assessing distal tissue perfusion in chronically ischemic limbs. This study compares ankle systolic pressure measurements with the transcutaneous oxygen tension results from the ischaemic foot with the patient sitting and found that the latter gave a more accurate guide to the severity of ischaemia and a more accurate prediction of the short-term results in individual cases.

Ankle↗
PubMed1988

Surgical management of long-term central venous access in uraemic patients.

Over a 5-year period, 1980-1985, 39 patients from a dialysis population of over 400 treated at this centre experienced major difficulties in achieving adequate access for dialysis by conventional techniques (i.e. arteriovenous fistula or CAPD). This study has evaluated the long-term results of a new approach to circulatory access, central venous catheterisation (CVC) for so called "high risk" patients. CVC consists of inserting a single-lumen CAPD-type silastic catheter into the right atrium via an external or internal jugular vein. Forty-seven catheters have been inserted into 39 uraemic patients. All patients had failed on, or were unsuitable for, conventional access to haemodialysis or CAPD. Ten patients (26%) had previous failed renal transplants. The median duration of catheter use was 7 months (range 1-60 months) and a total of 6500 high-performance dialyses have been performed using this technique. No patient has died of catheter-related problems. The catheters were easily managed by nurses and well tolerated by the patients. The incidence of complications among patients was low: displacement (1), catheter thrombosis (2), skin exit-site infections (5), septicaemia (2). Central venous catheterisation is a method of providing safe and reliable long-term vascular access which is immediately usable by high-risk patients who have either failed on or are unsuitable for conventional circulatory access.

Adolescent↗
PubMed1987

A rapid, objective method for the detection of lymphocytotoxic antibodies using flow cytometry.

Whilst several centres have reported lymphocytotoxic antibody detection using single and dual fluorescent stains with analysis of the fluorescence emitted from the cell population present in a well of a multiwell plate, problems are encountered with cell concentration and light emission overlap. A method we have developed using flow cytometry produces similar values of percentage cell death using single or double staining techniques (correlation coefficient = 0.9896). This method is not influenced by slight variation in cell number or light emission overlap. The effect of introducing red cell impurities into the normal lymphocyte preparation is described.

Antilymphocyte Serum↗
PubMed1987

Specific and nonspecific immunoregulatory factors and renal transplantation.

From a study population of 208 consecutive first cadaver renal transplant recipients a proportional hazard model was used to simultaneously quantify the role in graft failure of matching for specific HLA antigens and constitutional factors (age, sex, duration of dialysis (Dt), and pre- (PTr) and peri-(PerTr) operative transfusions) that influence nonspecific immune response. A comparison was also made of graft survival in patients treated by the two principal methods of dialysis, hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). The advisability of including nonimmunological failures in studies of graft survival was also considered. The analysis indicated that factors influencing a patient's innate nonspecific immune response (e.g., Dt and PTr) are important determinants of graft survival and should be taken into account when considering matching for specific HLA-B or DR antigens prior to transplantation. While there was no overall effect of dialysis type on graft survival, the influence of other risk factors depended on the method of dialysis. Failure to identify and exclude graft loss for nonimmunological reasons can give rise to misleading conclusions in analysis of immunoregulatory factors in organ transplantation.

Blood Transfusion↗