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Biomedical subjects

P J Friend

Publications and source records attributed to P J Friend.

At least 37 records · Page 2Linked to original sources
PubMed1999

Campath IH allows low-dose cyclosporine monotherapy in 31 cadaveric renal allograft recipients.

BACKGROUND: Campath 1H is a depleting, humanized anti-CD52 monoclonal antibody that has now been used in 31 renal allograft recipients. The results have been very encouraging and are presented herein. METHODS: Campath 1H was administered, intravenously, in a dose of 20 mg, on day 0 and day 1 after renal transplant. Low-dose cyclosporine (Neoral) was then initiated at 72 hr after transplant. These patients were maintained on low-dose monotherapy with cyclosporine. RESULTS: At present, the mean follow-up is 21 months (range: 15-28 months). All but one patient are alive and 29 have intact functioning grafts. There have been six separate episodes of steroid-responsive rejection. One patient has had a recurrence of her original disease. Two patients have suffered from opportunistic infections, which responded to therapy. One patient has died secondary to ischemic cardiac failure. CONCLUSIONS: Campath 1H has resulted in acceptable outcomes in this group of renal allograft recipients. This novel therapy is of equal efficacy compared to conventional triple therapy, but allows the patient to be steroid-free and to be maintained on very-low-dose immunosuppressive monotherapy.

Adult↗
PubMed1999

Anti-globulin responses to rat and humanized CAMPATH-1 monoclonal antibody used to treat transplant rejection.

BACKGROUND: Antiglobulin responses are a significant limitation to the repeated use of murine monoclonal antibodies for treatment of transplant rejection. It is hoped that these might be largely overcome by using antibodies genetically engineered to resemble human antibodies. METHODS: We have compared the responses in patients treated with the CD52 monoclonal antibodies CAMPATH-1G (rat IgG2b) or its humanized derivative, CAMPATH-1H (human immunoglobulin G1). RESULTS: A majority of patients (15 of 17) made responses to the rat antibody, but there were no detectable responses to the humanized antibody (0 of 12). CONCLUSIONS: Although anti-idiotype responses are theoretically possible against humanized therapeutic antibodies and are especially likely to be provoked by cell-binding antibodies, these data show that humanization offers a significant reduction in immunogenicity, potentially allowing repeat courses of treatment.

Alemtuzumab↗
PubMed1999

Sirolimus: a potent new immunosuppressant for liver transplantation.

BACKGROUND: Sirolimus (rapamycin) is a new immunosuppressant that appears to be synergistic with cyclosporine in kidney transplantation, but with a different side-effect profile. This pilot study evaluated sirolimus in liver transplantation. METHODS: Patients undergoing orthotopic liver transplantation for primary tumors (8), and later for nonmalignant disease (7), received one of three sirolimus-based immunosuppressive regimens. Protocol A comprised sirolimus, microemulsion cyclosporine (target whole blood concentration: 100 ng/ml), and prednisolone; protocol B omitted prednisolone; and protocol C was sirolimus alone. By 3 months after transplantation, all patients were receiving sirolimus as monotherapy. RESULTS: Fifteen patients were treated with a follow-up of 117-806 days. Rejection was more common on monotherapy than double therapy, and absent on triple therapy. The drug was generally well tolerated, with only three patients discontinuing sirolimus: one for hyperlipidemia, one for pneumocystis pneumonia, and one for inability to tolerate the taste of the drug. Two patients discontinued cyclosporine early, both as a result of neurological complications; they continued on sirolimus monotherapy. Five patients died; one suffered a cardiac arrest, and four died from sepsis in association with graft-versus-host disease, recurrent tumor, a paralyzed right hemidiaphragm, and primary nonfunction. CONCLUSIONS: Sirolimus combined with cyclosporine provided potent immunosuppression of liver allografts, and sirolimus monotherapy was adequate and well tolerated as maintenance therapy. Side effects of sirolimus over the short period of follow-up were uncommon and reversible with dose reduction or cessation of therapy.

Adult↗
PubMed1998

Graft loss and the antiphospholipid syndrome following liver transplantation.

BACKGROUND/AIMS: The antiphospholipid syndrome is characterised by arterial and venous thromboses affecting small and large vessels, together with the presence of lupus anticoagulant and anticardiolipin antibodies. METHODS: We report two cases of the antiphospholipid syndrome following liver transplantation which resulted in hepatic vessel thrombosis and subsequent graft loss, and we discuss the value of anticoagulation in prevention of further thrombotic episodes. Identification of these cases prompted a retrospective analysis for the presence of IgG anticardiolipin antibody, the most useful laboratory marker of vascular thrombosis in the antiphospholipid syndrome. Serum taken at 2 to 4 weeks following transplantation (when thrombotic events might be anticipated) was analysed further in 132 patients undergoing liver transplantation. RESULTS: Hepatic vessel thrombosis occurred in 21/132 (16%) post transplantation. Anticardiolipin IgG was present in 2/21 (8.8%) recipients who developed a hepatic vessel thrombosis following liver transplantation, compared to 7/111 (6.3%) (p=0.59) in whom transplantation was not complicated by hepatic vessel thrombosis. CONCLUSIONS: The presence of IgG anticardiolipin antibody was uncommon in recipients following liver transplantation and was not associated with an increased risk of hepatic vessel thrombosis. In contrast, the antiphospholipid syndrome which is rare may result in hepatic artery occlusion and graft loss, and so prompt recognition of the clinical syndrome is critical. Although screening for the antibody is not warranted in liver transplant recipients, it is important to be aware of the syndrome as optimal management of such cases may prevent graft loss.

Antibodies, Anticardiolipin↗
PubMed1997

Randomized trial to evaluate the clinical benefits of serum alpha-glutathione S-transferase concentration monitoring after liver transplantation.

BACKGROUND: An increase in serum alpha-glutathione S-transferase concentration (GST) has been shown to be a more sensitive and specific marker of hepatocellular damage than equivalent increases in transaminase activities. A randomized clinical trial of 60 liver transplants in 49 patients was carried out to assess the clinical benefits of GST monitoring as a supplementary test to routine liver function tests during the first 3 postoperative months after liver transplantation. METHODS: Mortality and morbidity were compared in graft recipients who had their GST reported daily to the ward (reporting group) and graft recipients who did not. RESULTS: The 3-month survival rate was significantly greater in the reporting group (P=0.033) and the risk of graft loss was halved (relative hazard ratio=0.50; P=0.29). The reporting group also had significantly more patients who spent less than 3 weeks in the hospital throughout the follow-up period (P=0.036). In addition, the reporting group experienced a lower frequency of biopsies per graft (P=0.038), less severe rejection (P=0.015), and a lower incidence of infection episodes per graft (P=0.03). GST increased by >50% above the upper limit of the reference range at a median of 1 day before the equivalent change in alanine transaminase in association with allograft rejection in the combined groups (95% confidence interval=1 to 2 days) but was lower on the day of diagnosis of rejection in the reporting group (P=0.02). This is compatible with the earlier diagnosis of rejection in the reporting group. CONCLUSIONS: We conclude that the monitoring of GST may improve patient care, reducing both mortality and morbidity.

Adult↗
PubMed1997

Multiple frequency bioimpedance: a bed-side technique for assessment of fluid shift patterns in a patient with severe dehydration.

This report describes the use of multiple frequency bioimpedance analysis (MFBIA) to monitor fluid changes in a patient who developed severe dehydration and recovered. Initially, the patient weighed 53.2 kg, his total body water (TBW; D(2)0 dilution) was 33.5 L, his extracellular water (ECW; Br dilution) was 19.5 L, and hydration of the fat-free mass (FFM; dual-energy X-ray absorptiometry) was normal (73%). The resistances at infinite and 0 frequency were R(inf) = 454 and R(0) = 580 ohm respectively, which predicted TBW = 33.1 L and ECW = 16.6 L. On day 7, when the weight loss was 7.2 kg, FFM had decreased by 7.4 kg, and R(inf) and R(0) had increased to 662 and 902 ohm respectively, predicting decreases of 5.8 L in TBW and 3.7 L in ECW. On recovery (day 14), all parameters had returned to baseline values. This study encourages the use of MFBIA as a bed-side technique for the serial assessment of body water compartments in patients with disturbances in fluid balance.

Journal Article↗
PubMed1997

Novel strategies for liver support in acute liver failure.

At present, the treatment of a patient in acute liver failure is based upon scrupulous intensive care. In those patients whose condition deteriorates, emergency liver transplantation must be considered. There would be great benefit if it were possible to provide treatment which would stabilise the condition of a patient in acute liver failure. Thus, there is great incentive to develop a means of artificial liver support. Over many years, a considerable array of therapeutic strategies has been investigated. These can be considered in four main categories: plasma exchange, haemofiltration, extra-corporeal liver assist devices (ELAD), extra-corporeal liver perfusion (ECLP). Finally, the role of xenotransplantation is considered.

Animals↗
PubMed1997

Recent developments in transplantation of the small intestine.

The widespread application of intestinal transplantation depends upon achieving a success rate sufficiently high to warrant treating patients by transplantation rather than parenteral nutrition. This is analogous to the situation in renal transplantation (where the alternative is dialysis) and pancreatic transplantation (insulin treatment) and contrasts with the situation in liver and heart transplantation where there is no effective alternative therapy. The main barrier to success at this level is immunological; progress will depend on improved prevention, diagnosis and treatment of rejection. Although developments are expected of new and more potent immunosuppressive drugs, it is possible that acceptable long-term results will require a more fundamental manipulation of the immune response in order to achieve at least partial tolerance of the graft.

Graft Rejection↗
PubMed1996

Radionuclide studies in intestinal transplantation. Diagnosis of rejection and assessment of permeability.

Three patients who received intestinal allografts were studied using two distinct radionuclide investigations. In the first, 111In or 99mTc-labeled leukocyte scanning was performed to assist in the diagnosis of rejection. It was able to demonstrate the occurrence of rejection in the transplanted intestine, and the response to antirejection therapy. In 1 case, the abnormality on the scan preceded the histological confirmation of rejection. The second technique studied mucosal integrity by serial 51Cr-EDTA/14C-mannitol permeability tests. These studies demonstrated the initial marked impairment and the slow return to normal function of the intestinal mucosal barrier. In 1 patient, this occurred by 91 days; in another, it took 232 days. A single assay performed in the third patient at the time of allograft rejection was also abnormal. Both radionuclide tests were helpful in the care of these complicated cases.

Adult↗
PubMed1996

Donor arterial variations in liver transplantation: management and outcome of 527 consecutive grafts.

The impact of donor arterial variations and their management was investigated retrospectively in 527 consecutive allografts. Anomalous arteries were found in 161 grafts (30.6 per cent). There was no significant difference in the overall incidence of arterial complications between grafts with normal (3.6 per cent) and abnormal (5.6 per cent) anatomy. However, there was a higher incidence of arterial complications in transplants requiring multiple arterial anastomoses (P = 0.02), or anastomosis of donor vessels to recipient aorta with (P = 0.0003) or without (P = 0.04) an interposition graft for arterial reconstruction. The incidence of biliary complications was similar in grafts with a normal (18.8 per cent) or anomalous (18.0 per cent) arterial supply. Anomalies of hepatic arterial anatomy occur in one-third of all livers and do not compromise graft outcome unless multiple anastomoses or direct anastomosis to the recipient aorta are required for arterial reconstruction.

Aneurysm↗
PubMed1996

Successful use of size-mismatched liver allografts in children by delayed primary closure of the abdominal wall.

Children who are too ill to await a liver graft of suitable size may be transplanted with a relatively oversized graft by leaving the abdominal wound partially open, the defect reduced being bridged with polypropylene mesh and the mesh reduced in stages until it can be removed and the wound directly closed. This technique has been used in seven children who received nine grafts (five reduced and four full size). Their mean age was 7.3 (range 0.5-11) months and mean weight 5.8 (range 2.3-7.2) kg. Progressive reduction in the size of the transplanted liver made primary closure possible in survivors in up to four stages. Over a follow-up period of 3 to 58 months, five of the nine grafts and five of the seven patients survived. No significant complications attributable to the technique were encountered. The technique of delayed primary abdominal wall closure may be of benefit in children at risk of graft failure because of a size-mismatched graft.

Female↗
PubMed1996

Early increase in plasma parathyroid hormone levels following liver transplantation.

BACKGROUND/AIMS: The pathogenesis of post-transplantation bone loss is poorly understood, although glucocorticoid therapy is believed to play an important role. In the present study we have measured plasma parathyroid hormone concentrations in the first few months after orthotopic liver transplantation, in order to examine the potential contribution of hyperparathyroidism to bone disease. PATIENTS AND METHODS: Twenty-seven patients aged 32-54 years, 12 male, undergoing liver transplantation were studied prospectively before and for 3 months after operation. Plasma parathyroid hormone and serum 25-hydroxyvitamin D concentrations were measured by radioimmunoassay. RESULTS: Plasma parathyroid hormone levels were normal in all but two patients prior to transplantation. There was a highly significant increase in plasma parathyroid hormone concentrations at 1 and 2 months (p < 0.0005 and 0.001, respectively, versus baseline); by 3 months, values were close to those obtained preoperatively. Serum 25-hydroxyvitamin D concentrations showed no significant change over the study period. However, 74% of the patients had subnormal values at baseline. CONCLUSIONS: An early and transient increase in plasma parathyroid hormone after liver transplantation may be responsible for the high rates of bone loss which occur during the first few post-operative months. Prevention of post-transplantation bone disease is most likely to be achieved by peri-operative intervention with an anti-resorptive agent.

Adult↗