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Biomedical subjects

J R Chapman

Publications and source records attributed to J R Chapman.

At least 145 records · Page 8Linked to original sources
PubMed1987

Hypertension after renal transplantation. A comparison of cyclosporine and conventional immunosuppression.

Hypertension is a common complication after renal transplantation and is associated with increased mortality. Cyclosporine is known to be nephrotoxic and raises blood pressure in recipients of cardiac and bone marrow transplants, but there is conflicting data on the role of cyclosporine after renal transplantation. We have examined this question in patients entered into the second Oxford prospective randomized comparison of short-term cyclosporine treatment alone with conversion to azathioprine and prednisolone at 90 days (CsA group), and conventional therapy with azathioprine and prednisolone throughout (AP group). Blood pressure and antihypertensive medication were similar in the CsA and AP treatment groups during the first 90 days. Following conversion from cyclosporine, mean blood pressure fell from 155/94 to 142/81 within 7 days, and this fall correlated with the change in plasma creatinine over the same period (r = 0.44, P less than 0.05). Blood pressure was subsequently lower in the converted patients than in those treated with AP throughout. Six months after transplantation patients converted from cyclosporine not only had lower blood pressure but also required fewer antihypertensive drugs than AP patients. This study demonstrates that cyclosporine may elevate the blood pressure in recipients of renal transplants. This effect may either be direct or mediated through the effect of cyclosporine on renal function. Administration of corticosteroids during the first three months after transplantation is implicated as a possible cause of persisting high blood pressure.

Adult↗
PubMed1986

Irritable bowel syndrome: is a barium enema necessary?

A retrospective analysis was made of 114 new patients attending a gastroenterology clinic, in whom the initial clinical diagnosis was irritable bowel syndrome. Barium enemas were performed in 84 patients (74%), 15 of whom were found to have significant other disease. In each case this would have been suspected from the routine haematological and biochemical screening tests. It is suggested that, in the investigation of patients under 50 years of age presenting to a gastroenterology clinic with a typical history of irritable bowel syndrome, a barium enema should only be performed if the clinical examination, sigmoidoscopy, rectal biopsy or routine blood tests are abnormal. This policy would reduce substantially the number of normal barium enemas performed.

Adult↗
PubMed1986

Histology of and quantitative assays for oxazolone-induced allergic contact dermatitis in mice.

Oxazolone-induced allergic contact dermatitis in mice has been used as an in vivo model for identifying potential anti-inflammatory and immune-modulating drugs. Studies were conducted with this model to detail the histokinetics of the inflammatory response and to examine the adequacy of three assays for measuring the intensity of the inflammatory response when compared to histologic findings. CD-1 mice were sensitized with oxazolone on the flank and challenged on the dorsum of the ear pinna. The inflammatory response was quantitated by measuring the change in pinna weight and thickness and presence of 125I-2-deoxyuridine (125IUDR)-labeled cells. Cellular infiltrate was mixed with general predominance of mononuclear cells over neutrophils. Correlation with the histologic data suggests that both the ear weight and thickness assays are suitable primary screening assays, since both provided a sensitive, accurate and objective measure of the inflammatory response and its suppression by dexamethasone. The 125IUDR assay worked well in untreated mice but was unsatisfactory in mice treated topically or systemically with dexamethasone.

Administration, Topical↗
PubMed1986

Failure of platelet transfusion to improve human renal allograft survival.

Platelets, expressing only class I antigens on their surface, have been shown to improve renal allograft survival in some experimental models but do not lead to humoral sensitization. In this pilot study, 24 previously untransfused patients were given 3 platelet transfusions at 2-week intervals before renal transplantation. Twelve patients (group 1) received 200 X 10(8) platelets contaminated by 15 X 10(6) leukocytes in each transfusion, and 42% developed cytotoxic antibodies; 12 further patients (group 2) received a purified preparation containing 200 X 10(8) platelets and less than 5 X 10(6) leukocytes, and no cytotoxic antibodies were detected. Using a more sensitive flow cytometry technique, 83% of group 1 but only 17% of group 2 (P less than 0.004) responded to their platelet donors. From each group 9 patients have been transplanted. Four grafts in group 1 and 6 in group 2 have failed, yielding a 1-year graft survival rate of 44%, compared with 69% in blood-transfused patients (P = 0.03). Pure platelet transfusions, using our protocol, do not appear to improve renal allograft survival, and minimal contamination by leukocytes can lead to humoral sensitization.

Blood Transfusion↗
PubMed1986

Sequential analysis of HLA-class II antigen expression in human renal allografts. Induction of tubular class II antigens and correlation with clinical parameters.

The expression of HLA-class II antigens was assessed in 142 biopsies from 29 recipients of cadaveric renal allografts who received either short-term cyclosporine (n = 12) or azathioprine and low-dose prednisolone (n = 17). Biopsies were obtained before transplantation, routinely at days 7, 21, 90, and 365 after transplantation, and at other times as clinically indicated. Cryostat sections were labeled with monoclonal antibodies using an indirect immunoperoxidase technique. In all biopsies HLA-class II antigens were expressed on glomeruli and intertubular structures. In pretransplant biopsies proximal tubules expressed class II antigens, whereas distal tubules were always negative. After transplantation three patterns of class II expression were recognized based on renal tubular class II staining: normal, focal increased, and generalized increased expression. Sequential biopsy analysis showed fluctuating levels of expression in individual patients, which correlated with cellular infiltration and was associated with allograft rejection. 71% of biopsies obtained at day 90 from patients on conventional therapy showed increased class II expression compared with only 9% of biopsies from patients on cyclosporine immunosuppression. All patients with normal class II antigen expression in day 90 biopsies had well-functioning grafts two years after transplantation, whereas 3 of 9 with increased class II antigen expression had failed. Furthermore, all grafts failing from irreversible rejection before 90 days showed marked increase of class II antigen expression. The increased class II antigen expression in renal allografts may be merely a marker of rejection or may have a role in the augmentation of the response, either in its induction or as a target for the effector arm of the reaction.

Azathioprine↗
PubMed1986

Morphometric analysis of cellular infiltration assessed by monoclonal antibody labeling in sequential human renal allograft biopsies.

The mononuclear cell infiltrate in a total of 279 human renal allograft biopsies was determined by a panel of monoclonal antibodies using an indirect immunoperoxidase technique. Two hundred and seventy-two biopsies were obtained from 83 patients randomly allocated to receive short-term cyclosporine (CsA) or conventional azathioprine and low-dose prednisolone (AP). Biopsies were obtained routinely at days 0 (control biopsies), 7, 21, 90, and 365, as well as at other times when clinically indicated. A further 7 patients on AP therapy were biopsied several years after transplantation (median: 6 years 1 month). Morphometric analysis of cryostat tissue sections using a point-counting technique has shown that the infiltration in rejecting grafts is significantly greater than in grafts with stable function. However, significant infiltration also occurs within the first week after transplantation in grafts with stable function. While this infiltrate diminishes with time, it remains significant even in grafts biopsied several years after transplantation. The infiltration with CsA treatment is significantly less than with AP therapy. The magnitude of the infiltrate therefore varies with time, graft status, and immunosuppression. In contrast the phenotypic composition of the infiltrate remains relatively constant in all biopsies after transplantation with T lymphocytes (CD3+), accounting for approximately 35% of infiltrating cells and CD8+ cells more common than CD4+. Monocytes and macrophages account for most of the remainder of the infiltrate.

Antibodies, Monoclonal↗
PubMed1986

Immunoglobulin class and specificity of antibodies causing positive T cell crossmatches. Relationship to renal transplant outcome.

A group of 42 renal transplants performed in the presence of a T-cell-positive crossmatch were analyzed to determine the class and specificity of the donor-reactive cytotoxic antibodies. Dithiothreitol (DTT) was used to reduce IgM antibodies and a monoclonal antibody directed at a monomorphic determinant present on all HLA class I antigens (PA2.6) was used to inhibit cytotoxicity of anti-HLA class I antibodies. Sera from 26 of the positive crossmatches were considered to be autoreactive, and the positive crossmatch proved to be due to IgM and not directed at HLA class I in each case. One year graft survival was 100% in the 5 living-related and 60% in the 21 cadaver donor transplants, of which 10 were regrafts. Of the 42 positive crossmatches, 16 were not due to autoantibody. One was positive in the current serum taken at the time of transplantation, and this graft was rejected hyperacutely, while 15 were positive with peak but not current serum samples. Of the positive crossmatches, 12 were inhibited by PA2.6 demonstrating that they were directed at HLA class I antigens. PA2.6 inhibition could not be shown in 3 and in 1 DTT reduction was technically unsatisfactory. While 4 of the 7 positive crossmatches due to IgM antibodies were successful, the 7 transplants performed with positive crossmatches due to IgG antibodies all failed. DTT reduction and inhibition of cytotoxicity by PA2.6 helps to define positive crossmatches with donor T cells that are not associated with graft failure. Transplantation in the presence of a peak positive T cell crossmatch due to an anti-HLA antibody might only be successful if the antibody in the peak serum is of the IgM class.

Antibodies, Monoclonal↗
PubMed1985

Reversibility of cyclosporin nephrotoxicity after three months' treatment.

86 renal allograft recipients were randomly assigned to cyclosporin (Cy) for 90 days followed by azathioprine and prednisolone (Aza and P), or to Aza and P from day 0, as part of the second Oxford trial of short-term Cy use. All 62 patients whose grafts functioned for at least 120 days were included in this study. Serum creatinine was significantly higher in Cy-treated patients than in control patients from day 28 to day 90. Serum uric acid was also significantly higher in Cy-treated patients over the same period. Both creatinine and uric acid fell to the level of the control group after conversion to Aza and P. Serum uric acid was significantly higher for a given level of creatinine during Cy treatment than in either the control patients or the Cy-treated patients after their treatment had been changed to Aza and P. These data imply that Cy affects both the glomerular filtration rate and renal tubular function but that these effects are largely reversible.

Azathioprine↗
PubMed1985

Alloimmunisation to HLA antigens following transfusion with leucocyte-poor and purified platelet suspensions.

24 previously non-transfused patients were given three transfusions of 200 X 10(8) platelets at 14-day intervals. Group I (12 patients) received leucocyte-poor platelet suspensions with a mean contamination of 15 X 10(6) leucocytes per transfusion. Group II (12 patients) received platelets with less than 5 X 10(6) leucocytes per transfusion. 5 patients in group I and no patients in group II developed lymphocytotoxic antibodies (p = 0.037). Platelets with fewer than 5 X 10(6) leucocytes did not seem to stimulate a response to major histocompatibility antigens, but with a small contaminating dose of leucocytes appeared to be highly immunogenic.

Adolescent↗
PubMed1984

Humoral immune dysfunction as a result of prenatal exposure to diphenylhydantoin: correlation with the occurrence of physical defects.

The effect of prenatal exposure to diphenylhydantoin (DPH) on postnatal immune function of offspring was studied using a longitudinal experimental design and in vivo immunoassays. Maternal Balb/c mice were dosed by gavage on gestation days 9 through 18 with 0, 20, 40, or 60 mg/kg DPH. Humoral immune function was assessed by measuring the serum antibody levels to type III pneumococcal polysaccharide 5 days after immunization by radioimmunoassay. Cell-mediated immune function was assessed by measuring the delayed-type hypersensitivity response to the contact allergen oxazolone using a micrometer method. A dose-related suppression of humoral immune function was observed in male and female offspring at 25 days but not at 15 weeks of age. Cell-mediated immunity was not affected by prenatal DPH exposure at 25 days or 15 weeks of age. Offspring developed purulent eye exudates at 12 days of age; the incidence and persistence was related to DPH dose. The immunosuppressive effect of DPH on humoral immune function was significantly greater in offspring born with open eye defect than in similarly treated but physically normal offspring. The results suggest that prenatal exposure to DPH may adversely affect the normal development and expression of humoral immune function, particularly in those offspring with other manifestations of DPH's developmental toxicology.

Abnormalities, Drug-Induced↗
PubMed1984

Definition and clinical relevance of antibodies to nuclear ribonucleoprotein and other nuclear antigens in patients with cryptogenic fibrosing alveolitis.

Antinuclear antibodies (ANA) were studied in 122 patients with cryptogenic fibrosing alveolitis (CFA) and compared with age- and sex-matched control subjects. Fluorescent ANA were detected in 32% of the patients and showed a correlation with the presence of a systemic connective tissue disease; ANA were present in 6% of the control subjects, 21% of the patients with CFA alone, and 46% of those with CFA and an associated connective tissue disease. Antibodies to the defined nuclear antigens: deoxyribonucleic acid (DNA), nuclear ribonucleoprotein (nRNP), the Sm antigen, and Sjögren's syndrome A and B antigens (SS-A and SS-B) were examined to establish whether their presence was diagnostic of the associated diseases. Antibodies to DNA and Sm antigens identified 3 patients with CFA and systemic lupus erythematosus. The frequency of antibodies to SS-A and SS-B did not differ from that in control subjects. Antibodies to nRNP, detected in 15 (12%) of the patients (at a high titer in 5), were associated with females, the presence of Raynaud's phenomenon, and rheumatoid factor in the serum. However, despite the detection of these antibodies, none of these patients met fully the proposed criteria for the diagnosis of mixed connective tissue disease.

Adult↗
PubMed1983

Flow cytometric analysis of the effect of phenytoin and its major metabolite on mitogen stimulated mouse spleen cells.

The in vitro immunopharmacological effects of phenytoin (PHT) and its major metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) were investigated by flow cytometric analysis of the DNA content of mitogen stimulated mouse spleen cells. The qualitative effects of PHT and HPPH were similar in concanavalin A stimulated mouse spleen cells with both compounds causing an increase in the percentage of S phase cells. The data suggests that this effect is due to an augmentation of cell cycling as demonstrated by the significant increase in 4N cells in PHT treated cultures relative to control cultures following colcemid treatment. A PHT time course study revealed an increase in S phase cells and a subsequent increase in 4N cells. PHT had no significant effect on congenitally athymic nude mouse spleen cells stimulated with lipopolysaccharide (LPS) except at the highest concentration tested (80 micrograms/ml) where a depression of cell cycling was observed. HPPH caused a colcemid-like accumulation of 4N cells in the LPS stimulated nude mouse spleen cell cultures. PHT and HPPH were found to be effective in enhancing cell cycling in cultures containing a significant population of T-cells stimulated with a T-cell mitogen whereas an inhibitory effect was observed in cultures without T-cells stimulated with a B-cell mitogen. The capacity of PHT to enhance the mitogenic action of concanavalin A may relate to its capacity to induce immunologic abnormalities and lymphadenopathy in humans.

Animals↗