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Biomedical subjects

R M Higgins

Publications and source records attributed to R M Higgins.

At least 37 records · Page 2Linked to original sources
PubMed1996

Anticipation of highly sensitised renal patients' immunoadsorption requirements by prescreening using protein A minicolumns.

We are able to subdivide highly sensitised renal patients who wish to enter our immunoadsorption programme into two groups; those who will require acute pretransplant immunoadsorption only and those requiring regular immunoadsorption prior to transplantation. This division of patients is based on the results obtained from laboratory assessment using protein A minicolumns. Patient's plasma is passed down a minicolumn for 6 x 10 min cycles, a sample of plasma is kept after each cycle for analysis by cell flow cytometric cross-match (FCXM). The samples are screened against cells from two normal volunteers, one expressing a previously mismatched Class I HLA antigen (MMA) to which the patient has raised persistent IgG antibodies, the other, whilst not expressing any MMAs, should express a cross-reactive HLA Class I antigen (XRA) to which the patient has formed persistent IgG antibodies. Patients are allocated into the acute pretransplant immunoadsorption group if, after 6 minicolumn cycles, the T cell FCXM vs XRA and MMA is reduced to less than 1 Log median fluorescence intensity shift above the negative control and that both these values have been reduced by at least 15% from the preimmunoadsorption figure. If these criteria are not met, regular immunoadsorption is required under cover of cyclophosphamide. Eleven patients who have been allocated by these criteria have subsequently been transplanted without any incidence of hyperacute rejection.

Adolescent↗
PubMed1996

Antibody removal and subsequent transplantation of a highly sensitised paediatric renal patient.

We report a successful renal transplant in a highly sensitised paediatric recipient following removal of HLA-specific antibodies by extracorporeal immunoadsorption. The immediate pretransplant cytotoxic titre against the donor was greater than 1:512; this was reduced to negativity by two immunoadsorption sessions prior to transplant surgery. We also describe the presence of unexpected non-HLA-specific antibody activities in this immunoadsorbed patient.

Autoantibodies↗
PubMed1996

Treating paracetamol overdose by charcoal haemoperfusion and long-hours high-flux dialysis.

After serious paracetamol overdose, charcoal haemoperfusion was used to remove paracetamol from the circulation, aiming to reduce the severity of subsequent hepatic damage. Daily long-hours high-flux dialysis was given to patients with grade III-IV hepatic encephalopathy, and also to those at risk of developing encephalopathy. We reviewed patients treated in this manner who had not received N-acetylcysteine within the first 15 h after overdose. From January 1983 to January 1993, 73 patients with serious paracetamol overdose were seen, of whom 51 received charcoal haemoperfusion and/or high-flux dialysis. Patients who were admitted within the first 42 h after overdose and who received haemoperfusion and/or dialysis had significantly lower peak levels of prothrombin time, bilirubin and creatinine than those who were admitted after 42 h. Mortality was also lower amongst patients admitted before 42 h, at 2/18 (11%) vs. 15/33 (45%), p < 0.05.

Acetaminophen↗
PubMed1996

Vasculitis and rapidly progressive glomerulonephritis in the elderly.

The proportion of patients with vasculitis and rapidly progressive nephritis aged 70 years or over has risen from about 10% in the 1980s to over 30% in series reported in the 1990s. This study was undertaken to examine the presentation and outcome of such older patients. Seventeen of 56 patients (30%) who presented at two renal units were aged 70 years or over. Mean creatinine level at presentation was 530 mumol/l, and five patients received dialysis at presentation. Outcome was dependent on three factors, namely comorbid pathology, response to immunosuppressive therapy, and the occurrence in three cases of temporary spontaneous partial remission. Overall patient survival at one and two years was 62.5% and 50%, respectively, and 90% and 100% of surviving patients were independent of dialysis at one and two years, respectively. Response to chemotherapy was excellent, with full rehabilitation in many cases and no deaths directly attributable to adverse effects of immunosuppressive therapy. We conclude that diagnosis of vasculitis and rapidly progressive glomerulonephritis by renal biopsy and the subsequent administration of chemotherapy (including cyclophosphamide in many cases) resulted in a worthwhile benefit in these elderly patients.

Aged↗
PubMed1996

5-year follow-up of patients successfully transplanted after immunoadsorption to remove anti-HLA antibodies.

The function of renal allografts in patients who had received pretransplant immunoadsorption in order to remove cytotoxic anti-HLA antibodies was studied. We reviewed 6 patients who received a graft which functioned beyond 3 months; the mean follow-up period was 76 (range 62-89) months. Two grafts have been lost from chronic rejection, at 12 and 62 months, respectively. The mean plasma creatinine levels at 1 and 5 years were 169 (range 143-211) mumol/l and 155 (range 92-235) mumol/l, respectively (1.91, range 1.62-2.39, mg/dl and 1.75, range 1.04-2.66 mg/dl, respectively). The major source of morbidity during long-term follow-up has been the occurrence of renal artery stenosis in 5 patient and renal vein stenosis in 1. In conclusion, the 5-year graft survival and function was good in patients who received immunoadsorption and whose grafts survived beyond the first 3 months after transplantation.

Aged↗
PubMed1996

The pharmacokinetics of anti-thymocyte globulin (ATG) following intravenous infusion in man.

The pharmacokinetics of the distribution and elimination of polyclonal rabbit antithymocyte globulin (ATG) following intravenous infusion was studied in patients who had received renal allografts. ATG concentration was measured using a new enzyme-linked immunoabsorbent assay (ELISA) for the Fc portion of rabbit IgG. Eleven patients received 14 courses of ATG supplied either by Fresenius (F-ATG) or Merieux (M-ATG) as a daily infusion of 2-6 mg/kg body weight for a therapeutic course lasting 5-10 days. The washout phase of ATG elimination was analysed over 0-300 days; results were well-fitted by a single exponential decay (r2 > 0.95) giving a mean elimination half-life (t0.5e) of 29.8 days (range 14.3-45.0, n = 9). Data for the first 4 days of treatment were analysed with linear regression to obtain a mean value for the apparent volume of distribution of ATG (Vd) of 0.12 l/kg body weight (range 0.07 to 0.17, n = 5). These results demonstrate that rabbit ATG has a long half-life in human plasma and an apparent volume of distribution of about twice plasma volume. The relationship between the concentration of ATG measured by this Fc receptor assay and its biological activity requires further study.

Animals↗
PubMed1995

The quality of function of renal allografts is associated with donor age.

The quality of renal allograft function was assessed by prospective measurement of creatinine clearance at 1 year (n = 197) and at 3 years (n = 115) after cadaveric renal transplantation in a cohort of 268 patients treated with triple therapy immunosuppression. Donor age (P < 0.0012) and recipient age (P < 0.01) were independently associated with creatinine clearance both at 1 and at 3 years. In patients with donor age above 50 years and recipient age above 45 years, the mean creatinine clearance was 32.7 (SD 10.4) ml/min (n = 27). When the donor age was below 30 years and recipient age below 45 years, the mean creatinine clearance was 55.6 (SD 14.4) ml/min (n = 47, P < 0.001). However, in these patients there was no significant association between graft function and many of the factors known to influence graft survival, such as HLA matching, sensitisation of the recipient, and the occurrence of rejection. In conclusion, the quality of renal allograft function declined with increasing donor and recipient age in our patients, whilst immunological factors were not significantly associated with function in surviving grafts.

Adolescent↗
PubMed1995

Enhancement and inhibition of cellular responsiveness mediated by the anti-leucocyte monoclonal antibody NDS 71.

In this paper we describe the effects of a novel monoclonal antibody (mAb), which either inhibited or enhanced IL-2-stimulated proliferation of human peripheral blood leukocytes (PBL) at the same antibody concentration, under different culture conditions. An effect of this nature on IL-2-stimulated proliferation has not, to our knowledge, previously been described. The mAb NDS 71 bound to more than 98% of both freshly isolated and PHA-stimulated human PBL, with the level of binding markedly up-regulated on activation. An antigen of molecular weight 38-46 kDa was immunoprecipitated. When added to PBL at the beginning of in vitro culture, NDS 71 inhibited IL-2-stimulated proliferation. PHA-stimulated proliferation was enhanced by NDS 71 in identical conditions, demonstrating that the effects of NDS 71 on IL-2-stimulated proliferation were not merely due to non-specific inhibition of cellular proliferation. When NDS 71 was added to IL-2-stimulated PBL 4 h after the start of in vitro culture, proliferation was markedly enhanced, in contrast to the inhibition seen when the same concentration of antibody was added at the start of culture. In summary, NDS 71 markedly affected IL-2-stimulated proliferation, the same concentration of antibody causing either marked inhibition or enhancement, depending on the culture conditions.

Adjuvants, Immunologic↗
PubMed1995

Severe theophylline poisoning: charcoal haemoperfusion or haemodialysis?

Theophylline poisoning with a blood level of 183 mg/l in a 38-year-old man was treated with activated charcoal by mouth, but despite this the blood level of theophylline rose and there was circulatory collapse with rhabdomyolysis, acute renal failure and hyperthermia. Treatment with charcoal haemoperfusion and simultaneous haemodialysis was given, followed by continuous arteriovenous haemodialysis (CAVHD). Mean extraction rates of theophylline were 26% during CAVHD, and 86% during combined dialysis and charcoal haemoperfusion. During combined treatment, the mean extraction rate of haemodialysis was 62%, compared with 48% for charcoal haemoperfusion. In summary, activated charcoal given by mouth may be unable to prevent a rise in blood levels and the development of complications after substantial theophylline overdose. If theophylline is to be removed from the blood, a combination of charcoal haemoperfusion and haemodialysis will give the best clearance, but haemodialysis alone may be effective.

Adult↗
PubMed1995

Follow up of an immunocompromised contact group of a case of open pulmonary tuberculosis on a renal unit.

BACKGROUND: The organisation, management, outcome and cost of follow up of a large group of mainly immunocompromised patients and healthcare workers who were exposed to a staff member of a London renal unit with smear positive pulmonary tuberculosis are described. METHODS: Following British Thoracic Society (BTS) guidelines, 576 close contacts were identified and divided into three groups: (1) 303 renal patients including 61 with renal transplants; (2) 90 surgical patients; and (3) 183 staff members. Screened contacts were interviewed, completed a symptoms questionnaire, and were offered a chest radiograph and Heaf or Mantoux test if appropriate with referral to a chest physician if required. RESULTS: Overall, 524 (85%) living contacts have been screened: 243 (97%) renal (first screening), 63 (70%) surgical, and 135 (74%) staff contacts. Thirty one transplant patients were prescribed isoniazid chemoprophylaxis. Fifty two renal patients had died before screening and 11 deaths occurred after first interview. One case of tuberculosis epidemiologically related to the index case was diagnosed on clinical criteria. A review of the case records and/or death certificates and entries on to tuberculosis registers indicated no further cases. The cost of the investigation was estimated to be approximately franc25 000, or franc44 per contact screened, with staff costs comprising 79% of the total. CONCLUSIONS: Undiagnosed tuberculosis in healthcare workers working with immunosuppressed patients can lead to large and expensive follow up studies. The applicability of the 1990 and 1994 BTS guidelines to the investigation of tuberculosis in an immunocompromised nosocomial group, and the role of the infection control doctor and the consultant in Communicable Disease Control in overlapping nosocomial and community incidents, are discussed.

Adolescent↗
PubMed1994

Elective rather than emergency intervention for acute renal artery occlusion with anuria.

We describe a case in which surgical revascularisation was electively delayed until 27 days after acute renal artery occlusion, allowing surgery to be performed after a period of haemodialysis and pre-operative cardiac assessment. Owing to the collateral blood supply to the kidney, emergency surgery in cases of acute renal artery occlusion may not be necessary, and may be hazardous.

Acute Disease↗
PubMed1994

Presentation, clinical features and outcome in different patterns of atherosclerotic renovascular disease.

Atherosclerotic renovascular disease (ARD) is an increasingly important cause of renal failure. However, important features of the clinical presentation are not fully described, and the outcome after intervention by angioplasty remains controversial. Ninety-four patients with ARD diagnosed at angiography were reviewed. Twenty-four patients were diabetic. Thirty-nine patients had unilateral renal artery stenosis or occlusion (group A), 28 had bilateral stenosis (group B), and 27 had unilateral occlusion plus contralateral occlusion or stenosis (group C). Two years after presentation, actuarial patient survival was 96%, 74.3% and 47.1% in groups A, B and C, respectively (p < 0.001 for all differences); actuarial renal survival in surviving patients was 97.3%, 82.4% and 44.7%, respectively (p < 0.001 for all differences). Percutaneous transluminal balloon angioplasty (PCTA) was performed in 74 patients. Renal function improved in only a minority of cases, but was stable in 73% of nondiabetic patients 12 months after PCTA. Angioplasty was less effective in diabetic subjects, with only 53.3% having stable renal function at 12 months follow-up. Renal and patient survival were strongly related to the initial angiographic findings. In non-diabetic subjects, PCTA resulted in stabilization of renal function for at least one year in nearly three-quarters of cases, which suggests a benefit from intervention in this disease whose natural history is otherwise of progression.

Adult↗