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Biomedical subjects

R M Taylor

Publications and source records attributed to R M Taylor.

At least 127 records · Page 7Linked to original sources
PubMed1990

Zinc monoglycerolate: a slow-release source of zinc with anti-arthritic activity in rats.

Zinc repletion by parental administration of zinc monoglycerolate (ZMG) or certain other lipophilic zinc complexes, suppressed the development of adjuvant-induced polyarthritis in rats. While ZMG was effective when given parenterally over various limited time schedules (immunosuppressant, therapeutic, singledose), it was not effective given orally. The complex showed no acute anti-inflammatory activity in the carrageenan paw oedema assay and little gastric-intestinal or other organ toxicity. When injected s.c. it caused very much less local irritation than most zinc salts. Being lubrous, ZMG could be applied as the dry powder for rubbing into the skin and by this route was found to have anti-arthritic activity. 65Zn was shown to be absorbed and excreted in the faeces (biliary excretion) after applying 65Zn-ZMG dermally to shaved dorsal skin of rats. ZMG showed consistent anti-arthritic activity in rats under conditions in which 2 gold drugs (aurothiomalate, Auranofin) exhibited variable effects, depending on the strain of rat. The role of zinc and its availability in chronic inflammation are discussed on the basis of these studies.

Animals↗
PubMed1990

Monitoring of transplant patients' lymphocytes: knowledge of the varying specificities of anti-lymphocyte antibodies allows the interpretation of anomalous results.

In many transplant centers, the T lymphocytes of transplant patients are routinely monitored, both to predict and diagnose the cellular events that result from transplantation and to evaluate the effectiveness of immunosuppressive therapy. During the course of this monitoring, we have observed anomalous results: the number of T cells said to be present varies greatly depending on the surface marker used for the assay. It is shown, in this study, that these "anomalous" results can be predicted from a knowledge of the spectrum of specificity of the anti-lymphocyte antibody therapy being administered. Because polyclonal antibodies have varied and unstated specificities, it is difficult to interpret results obtained from monitoring T-cell numbers or subset ratios without some knowledge of the specificities of the drugs being used.

Antibodies↗
PubMed1990

Renal allograft rejection. Possible involvement of antibody-dependent cell-mediated cytotoxicity.

We have demonstrated that serum from appropriately sensitized patients can contain IgG antibodies that bind to cultured renal epithelial cells. The presence of such antibodies on the surface of renal cells enables otherwise nonlytic PBMC to lyse these renal cells by an antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. Experiments involving cell-sorting and specific complement-mediated lysis showed that the ADCC effector cells were of the CD3 -ve, C16 +ve phenotype characteristic of NK cells. In this report it is argued that an ADCC mechanism may be of importance in mediating chronic renal cell damage in the absence of acute allograft rejection.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1990

Cutaneous papillary squamous cell carcinoma. A report of two cases.

Several histologic patterns of squamous cell carcinomas (SCC) have been described, including classical, adenoid, verrucous, and clear cell. We report 2 cases of an unusual purely exophytic papillary growth pattern. Both tumors occurred on sun-exposed skin of elderly patients and exhibited rapid growth. The tumors were red-tan and fungating, raising the clinical differential diagnoses of pyogenic granuloma, SCC, metastatic carcinoma or amelanotic melanoma. Histologically there was a prominent papillary growth pattern with several layers of notably atypical squamous epithelium overlying a fibro-vascular core in both cases. Mitoses were frequent. The tumors lacked deep invasion, although focal invasion of the stalk was present. These tumors were histologically distinct from verrucous carcinoma, verrucous Bowen's disease, and previously described adnexal carcinomas. The lack of deep invasion and the absence of local recurrence or metastatic disease after 18 months follow-up suggest that this histologic variant is a low-grade malignancy, although study of more cases and longer follow-up will be necessary to accurately assess the biology of this papillary variant of SCC. We believe that this growth pattern has not yet been described and a pure papillary form must be included as one of the histological subtypes of cutaneous SCC.

Aged↗
PubMed1990

Late perfusion. A simple remedy for renal allograft primary nonfunction.

Primary nonfunction in renal allografts makes the diagnosis of allograft dysfunction more difficult and may effect long-term graft survival. The prevention of primary nonfunction by a reperfusion technique has been assessed in a prospective analysis of 145 consecutive renal transplants performed in a single center. All kidneys were retrieved using an in situ perfusion method, and all but 13 recipients received a standardized immunosuppressive protocol with cyclosporine. The first 106 transplants were performed without the benefit of any additional perfusion, and the incidence of primary nonfunction was 57.5% in these patients. The last 39 kidneys received additional perfusion with kidney perfusion fluid immediately prior to implantation (late perfusion). In the latter group, the incidence of primary nonfunction was 30.8% (P = 0.007). Using logistic regression analysis, only three factors were found to be associated with primary nonfunction: immunosuppression with cyclosporine (P = 0.01), a second warm ischemia time of greater than 35 min (P = 0.002), and late perfusion (P = 0.003). In this study, the use of late perfusion alone has reduced the incidence of primary nonfunction by almost one half. The technique is simple, safe, inexpensive, and effective. Its routine use is now advocated in all renal transplants.

Cyclosporins↗
PubMed1989

A flow cytometric technique for simultaneous analysis of human mononuclear cell surface antigens and DNA.

A method for dual staining of mononuclear cells for lymphocyte phenotypic markers and DNA is described. The cells were stained with fluorescein-conjugated monoclonal antibodies and then rendered permeable to propidium iodide using saponin. Propidium iodide stains DNA and, using flow cytometry, cell cycle analysis of individual lymphocyte subpopulations can be determined. Saponin acts within 1 min, preserves expression of surface antigens and is effective at all concentrations from 0.001% to 1%. This technique is simple, rapid and gives reproducible results.

Antigens, Surface↗
PubMed1989

Paget's disease.

Explore the source record for details and available documents.

Anus Neoplasms↗
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

Reproductive abnormalities in canine fucosidosis.

Male English springer spaniel dogs affected with fucosidosis, a lysosomal storage disorder, were found to be infertile while females with the disease reproduced successfully. Ejaculates of semen collected from affected dogs had reduced total sperm output and morphologically abnormal spermatozoa. A high proportion of ejaculated spermatozoa had midpiece droplets, bent tails and poor motility. Severely vacuolated epididymal epithelial cells were observed by light microscopy. Electron microscopic examination revealed membrane-bound vacuoles of variable size containing scanty amounts of granular to fibrillar material in epididymal epithelial cells, smooth muscle, myoid cells and Sertoli cells. Male infertility is believed to result from lysosomal storage of fucosyl-linked substrates in cells of the reproductive system. The extensive lesions in the epididymis may have interfered with maturation and transport of spermatozoa. Also, deficiency of alpha-L-fucosidase activity could have impaired the shedding of cytoplasmic droplets from spermatozoa and altered the surface glycoprotein composition of the sperm during epididymal transit.

Animals↗
PubMed1989

A phase I study of immunostimulation and toxicity in patients with colorectal carcinoma using the immunomodulator 3,6-bis(2-piperidinoethoxy) acridine trihydrochloride (CL 246738).

Seventeen patients with residual or recurrent colorectal carcinoma were given a new synthetic immunomodulator [3,6-bis(2-piperidinoethoxy) acridine trihydrochloride CL246738) as part of a phase I clinical trial. No patients had undergone previous immunotherapy or chemotherapy. Detailed immunological studies including interferon levels, interleukin 2 levels, natural killer cell function, mitogen responses of lymphocytes, immunoglobulin levels and lymphocyte subpopulation levels were analysed in the patients who received this drug in an attempt to find out whether there was any biological activity identifiable in humans. None of the subjects showed any significant increases in post treatment values of the immunological parameters studied. Toxic effects of the drug at high doses included nausea, diarrhoea and decreased levels of consciousness. In conclusion, no immunological effects were identified following the administration of CL 246738 in human subjects with recurrent or residual colorectal cancer.

Acridines↗
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

Ethical aspects of medical economics.

The fundamental problem of economics is how best to satisfy human needs and desires in the face of limited resources. Any benefit achieved by expending resources for one purpose is offset by an "opportunity cost": The opportunity to use those resources for other purposes is lost. Whenever resources are used to provide one medical benefit, a choice is made not to provide other benefits. The opportunity costs of medical care choices are rarely acknowledged; thus the ethical implications of such choices are rarely explicitly stated. Rationing of medical care is inevitable; how to ration our resources must be openly debated within an ethical framework. Individual physicians have an ethical obligation to avoid wasteful and unnecessary expenditures of the resources allocated to medical care. Society has an obligation to confront the ethical dilemmas implicit in health care allocation and rationing decisions. Although perhaps less painful, avoiding difficult choices is less ethical than confronting them.

Economics, Medical↗