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Biomedical subjects

A D Mayer

Publications and source records attributed to A D Mayer.

At least 73 records · Page 4Linked to original sources
PubMed1995

Therapeutic drug monitoring of tacrolimus in clinical transplantation.

Initial clinical trials of FK did not incorporate available FK levels, and difficulties were quickly experienced particularly with neurotoxicity and nephrotoxicity. The introduction of routine assay allowed broad parameters to be identified, which assisted in evaluating effective therapeutic parameters. Levels approximately 20 ng/ml were frequently associated with toxicity and the initial therapeutic range between 10-25 ng/ml was probably excessive. Reliable effective assay > 5 ng/ml using the Abbott IMx is not available, and many patients will have excellent hepatic or renal function with what are currently undetectable levels of FK. However, IncStar have an ELISA assay with a sensitivity of 0.5 mg/ml. Clinical practice does not, at this time, dictate elevation of FK, although careful monitoring continues. Education of oral administration from 0.15 mg/kg to 0.1 mg/kg in combination therapy with steroids and 0.05 mg/kg with azathioprine and steroids has led to revision of therapeutic parameters, e.g., 5-15 ng/ml is now widely used. Therapeutic drug monitoring is important to avoid unnecessary toxicity, but the lower limit has not been fully defined. Clearly, many patients with < 5 ng/ml have excellent hepatic function.

Drug Monitoring↗
PubMed1995

Nutritional care and candidates for small bowel transplantation.

Twenty two children were evaluated for small bowel transplantation between 1989 and 1994. Eight were unfit for transplantation and died within three months; a raised plasma bilirubin concentration (> 200 mumol/l) predicted death from liver failure within six months (p = 0.0001). The 11 children who were not managed by a multidisciplinary nutritional care team were less well nourished at referral, had more complications with intravenous feeding catheters, and greater early mortality while awaiting transplantation (p < 0.05). It is recommended that children with chronic intestinal failure be referred for assessment early, before liver dysfunction is established.

Adolescent↗
PubMed1995

Restorative proctocolectomy and pouch anal anastomosis for ulcerative colitis following orthotopic liver transplantation.

This study reports on the outcome of four patients having ileal pouch anal anastomosis after orthotopic liver transplantation for sclerosing cholangitis complicating ulcerative colitis. There were no deaths on follow up. Early postoperative bleeding was a complication of colectomy or rectal excision in three, one of whom developed hepatic artery thrombosis and the overall complication rate was high. All patients are continent but one has chronic pouchitis (while receiving longterm metronidazole) and one patient has recurrent sclerosing cholangitis in the transplant.

Adult↗
PubMed1994

Policies in Europe on "marginal quality" donor livers.

Shortage of donor livers has led several liver transplant centres to widen their definition of liver donor suitability. We have assessed the function of liver grafts from "marginal" donors and attitudes to use of such organs. Over an 18-month period, livers used in 30 of 213 consecutive liver transplantations in Birmingham, UK, came from marginal donors (history of alcoholism, abnormal liver function test results, drug overdose that included paracetamol, advanced cardiovascular disease, sepsis, lengthy hypotension [systolic blood pressure < 80 mm Hg for > 1 h], high-dose inotropic drug use). 16 of these donors had been refused by other UK liver transplant centres, 11 on medical grounds. The controls were grafts retrieved from "good" donors (n = 183) during the same period. All 30 grafts showed satisfactory early function but had greater day 1 (p = 0.004) and peak serum aspartate aminotransferase (p = 0.0008) values than control grafts. Graft and patient survival at 1 year in the two groups was similar (72% vs 73% and 80% vs 82%, respectively). To assess attitudes to marginal donor livers, a questionnaire outlining the details of these 30 donors was sent to the 80 centres in the European Liver Transplant Group, and 60 replied. Median immediate refusal rate of the marginal donors was 7/30 (range 0-18) and median outright acceptance rate was only 11/30 (1-26). Larger centres were less selective, with a significantly lower refusal rate (p = 0.03). These results indicate that, because of existing liver donor criteria within Europe, usable donor livers are being unnecessarily refused on medical grounds.

Adolescent↗
PubMed1994

Extended preservation of the liver with UW solution--is it justifiable?

The outcome of 228 liver grafts in 208 elective adult recipients was assessed to identify any adverse effects of extending the length of cold preservation with UW solution beyond 12 hr. A total of 114 grafts had been preserved < 12 hr--median 9.5 (group I) and 114 > 12 hr--median 14.5 (group II). Intraoperative blood and blood product usage, graft function, hospital stay, and graft and patient survival were identical in the two groups. Biliary strictures occurred in 5.7% of grafts (8 anastomotic (3 group I, 5 group II; 5 hilar/nonanastomotic: 3 group I, 2 group II). There was no graft or patient loss due to the hilar strictures but 1 patient died following reconstruction of an anastomotic stricture (0.4%). It is concluded that extending the cold preservation to approximately 15 hr does not adversely affect outcome after liver transplantation.

Adenosine↗
PubMed1994

The role of dynamic and morphological studies in the assessment of potential liver donors.

In a prospective study, 66 donor livers were evaluated by monoethylglycinexylidide (MEGX) dynamic clearance and semiquantitative scoring of pathological changes in liver biopsies. The median MEGX level in 63 donors was 89 mcg/L (range 16-250 mcg/L); fifteen had MEGX levels < 50 mcg/L, 17 between 50 and 90 mcg/L, and 31 > 90 mcg/L. There were no cases of primary nonfunction, and no deaths were related to poor graft function. There was no statistically significant difference in peak aspartate aminotransferase (AST), day 5 AST, peak bilirubin, or lowest prothrombin time among the 3 groups. Liver biopsies were assessed in 61 donors: 33 (54%) were normal and 17 (28%) showed mild, 8 (13%) showed moderate, and 3 (5%) showed severe steatosis. Postperfusion biopsy assessing the extent of preservation injury was essentially normal or showed minimal change in 16 (26%), mild change in 29 (48%), moderate in 13 (21%) and severe abnormalities in 3 (5%). The latter 3 biopsies all had severe steatosis. There was no significant difference in early graft function or outcome between moderate/severe groups and normal/minimal groups, although the former had a higher peak AST (P < 0.02) and peak bilirubin (P < 0.004). This detailed prospective analysis suggests that MEGX and the morphological studies may assist in the assessment of potential liver donors but they do not provide a basis on which grafts should be discarded.

Adolescent↗
PubMed1994

Donor thyroid function does not affect outcome in orthotopic liver transplantation.

Brainstem death is associated with endocrine and metabolic alterations that can result in donor hemodynamic instability. It has been suggested that these changes can be reversed through hormonal manipulation of the donor. We measured thyroid hormone levels (free triiodothyronine [fT3], free tetraiodothyronine [fT4], reverse triiodothyronine) and thyroid-stimulating hormone (TSH) in 50 consecutive adult brain dead multiorgan donors. Recipient graft function was assessed using peak and day 5 aspartate aminotransferase, peak serum bilirubin, and minimum prothrombin time during the first week after OLT. Free T3 was low in 32/50 donors and was associated with a low fT4 in 24 cases. TSH was normal in 35 donors and we found no correlation between TSH levels and fT3 or fT4. Reverse triiodothyronine was normal or high in 96% of donors. Patient and graft survival were 96% for both the low and high fT3 groups. These data suggest that euthyroid sick syndrome is the most likely cause for the endocrine and metabolic alterations seen in brainstem-dead donors. This does not appear to influence liver recipient or graft survival.

Adolescent↗
PubMed1994

Steroid withdrawal 3 months after liver transplantation--does FK 506 confer any advantage over cyclosporin?

Eighty-one liver recipients were randomised to FK 506 or cyclosporin (CyA) and azathioprine (AzA), both in combination with steroids. Twenty-seven FK 506 and 29 CyA/AzA patients continued in the trial 3 months after transplantation. Steroids were ceased in 23 (85%) FK 506 patients and in 27 (93%) CyA patients. After steroid withdrawal, 2 FK 506 and 4 CyA patients were excluded from the study, all for reasons other than rejection. The median follow-up was 16 months for the FK 506, and 19 months for CyA group. There were no acute rejection episodes or graft losses in the FK 506 group. None of the CyA patients lost their graft but three (13%) had episodes of acute rejection requiring steroids to be recommenced in two cases. There was no evidence of chronic rejection in any of the annual review biopsies in either group. Our results suggested no advantage of FK 506 over CyA in its steroid-sparing effect.

Adolescent↗
PubMed1994

The immunomodulatory effects of a novel agent, leflunomide, in rat cardiac allotransplantation.

We assessed the immunomodulatory effect of leflunomide (LEF) in a heterotopic abdominal model of rat heart transplantation using a major histocompatibility mismatch (DA X LEW). The endpoint of this study was cardiac rejection assessed by abdominal palpation of the ventricular impulse and confirmed by laparotomy and histology. In this study, LF was investigated using four dosages (5, 10, 20 and 30 mg/kg per day orally) against cyclosporine (CsA) (15 mg/kg per day orally) and FK 506 (1 mg/kg per day orally). The ability of LEF to prevent rejection and reverse ongoing acute rejection was assessed. The results showed that untreated hearts were fully rejected by day 5 and that LEF at 5 mg/kg was significantly better than any other dose tested, was superior to FK 1 mg/kg, and was as effective as CsA 15 mg/kg in preventing rejection after a short course of treatment. After a longer course, 10 and 20 mg/kg LEF proved more effective than 5 mg/kg in controlling rejection and as efficacious as 1 mg/kg FK and 15 mg/kg CsA. In the control of ongoing established early rejection. LEF proved to be equally effective, even at lower doses (5 mg/kg), to CsA 15 mg/kg and FK 1 mg/kg. In the control of ongoing established late rejection, 20 mg/kg LEF proved to be superior to 10 mg/kg LEF and 15 mg/kg CsA, and was as effective as FK 1 mg/kg. However, when higher doses of CsA (25 mg/kg) and FK (2 mg/kg) were tested against 20 mg/kg LEF in this mode of rescue, LEF proved as effective as CsA and superior to FK. In the assessment of drug toxicity using body weight as a parameter, 20 mg/kg LEF proved safer than any other LEF dose tested, and safer than 15 mg/kg CsA and 1 mg/kg FK in both short- and long term administration. We conclude that LEF is a relatively safe and potent immunosuppressant with promising clinical potential.

Animals↗
PubMed1994

Serious paracetamol poisoning and the results of liver transplantation.

Paracetamol poisoning is the most common cause of fulminant liver failure in the United Kingdom. An accurate assessment of prognosis at the time of referral will allow the appropriate application of liver transplantation in this setting. The outcome of 92 patients consecutively admitted to a specialist liver unit with severe poisoning has been examined. In patients who did not have a transplant, a fatal outcome was seen for 26/82 (32%), and was associated with late presentation, coma grade, prothrombin time prolongation, metabolic acidosis, and renal dysfunction. Cerebral oedema, and sepsis were responsible for most deaths. Prognostic criteria defined at King's College Hospital seemed to predict the outcome of patients who did not have a transplant managed on the Birmingham liver unit. Seventeen patients were listed for transplantation, 10 had liver transplantation, and seven of 10 survived. Seven were listed but not transplanted, and one of seven survived. Psychological rehabilitation of patients who had a transplant has not proved difficult. These results suggest a role for liver transplantation in the management of selected patients with paracetamol poisoning.

Acetaminophen↗
PubMed1993

Successful liver transplantation in babies under 1 year.

OBJECTIVE: To review the outcome of liver transplantation in babies aged less than 1 year. DESIGN: Prospective evaluation of survival, clinical complications, and nutritional and developmental status before and one year after liver transplantation. SETTING: The Children's Hospital and Queen Elizabeth Hospital, Birmingham. SUBJECTS: All 25 babies who received liver transplantation from January 1989 to December 1992 were included. Median age was 9 months and median weight was 7.0 kg. Seven babies were assessed but were not given transplants because they died while on the waiting list (two) or had severe extrahepatic disease (five). RESULTS: 24 babies had severe decompensated liver disease and 20 were severely malnourished despite nutritional support. Six babies received a whole liver graft and 19 received a reduction hepatectomy. Postoperative complications included primary nonfunction of the transplanted liver (one baby), hepatic artery thrombosis (two), biliary obstruction (seven), acute and chronic rejection (six), and sepsis (18). Three babies required a second transplant; all survived. Three babies, two of whom presented with fulminant hepatic failure, died. The overall actuarial survival rate (4 months to 4 years) is 88%. Review at 12 months showed a dramatic improvement in growth (p < 0.001) and normal psychosocial development with good quality of life. CONCLUSION: The improvement in survival rates and quality of life in this group of very sick babies is related not only to the development of reduction hepatectomy but also to advances in medical and nursing expertise. Early referral for liver transplantation is justified even if babies are critically ill.

Anthropometry↗