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Biomedical subjects

S V Lynch

Publications and source records attributed to S V Lynch.

At least 73 records · Page 4Linked to original sources

Lignocaine metabolism and liver function testing in primary graft failure following orthotopic liver transplantation.

OBJECTIVE: To report the use of lignocaine and the measurement of its metabolite, monoethylglycinexylidide (MEGX), as a dynamic test of liver function. CLINICAL FEATURES: The conversion of lignocaine to MEGX has been used serially as a test of liver function in a liver transplant recipient for whom retransplantation was necessary because of primary non-function (PNF) of the initial graft. MEGX concentrations were markedly depressed with individual episodes of PNF, cardiac failure and rejection in this patient. CONCLUSION: The test provided useful additional supportive information in assessment of the patient and management of intercurrent problems following liver transplantation.

Female↗

The effect of a prostaglandin I2 analogue (OP-41483) on energy metabolism in liver preservation and its relation to lipid peroxidative reperfusion injury in rats.

The effect of the stable prostacyclin (PGI2) analogue OP-41483 (OP) on liver preservation was investigated in the rat liver transplant model. In a 1-week survival study, 33 orthotopic liver transplants were performed using Wistar rats. In group A, untreated livers were stored with modified UW (mUW) solution at 4 degrees C. In group B, livers from OP-pretreated donors (2 micrograms/kg, i.v.) were stored with mUW solution containing OP (1 microgram/ml) at 4 degrees C. After 24 h storage, the donor grafts in each group were transplanted to untreated recipients. OP treatment (group B) significantly improved 1-week survival (62.5%, 10/16, P < 0.01 versus group A; 11.8%, 2/17). For the measurement of adenine nucleotides and lipid peroxidation (malondialdehyde, MDA) in liver tissue before preservation, after preservation, and 3 h after transplantation, 20 rat livers in groups A and B were studied. In both groups, the levels of adenosine triphosphate (ATP) declined 6 h after cold preservation, but this degradation of ATP was significantly halted at the level of adenosine monophosphate (AMP) in the OP-treated livers after 24 h of storage. However, OP treatment showed no significant difference in the degree of ATP recovery after transplantation. On the other hand, OP treatment resulted in suppression of the increase in MDA levels and histological amelioration of microcirculatory disturbance 3 h after transplantation. Our data suggested that the combined use of the stable PGI2 analog (OP-41483) and UW solution is beneficial in liver preservation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

A new technique for early detection of portal vein and arterial thromboses. Indwelling mesenteric venous catheterization and relevance to small bowel transplantation.

The aim of this study was to ascertain whether, in an animal model, continuous monitoring of mesenteric venous pressure (MVP) via an indwelling mesenteric venous catheter could assist in early detection of thrombosis of the portal vein (PVT) and superior mesenteric artery (SMAT). The role of portography via the catheter was also studied in confirming these complications. An animal model of PVT and SMAT was developed in pigs. At laparotomy, a 20-cm jejunal loop was isolated and a heparin-coated catheter was inserted into a mesenteric vein of the isolated jejunum and connected to a pressure transducer. Conditions of PVT were simulated by progressive occlusion of the portal vein (PV) using a silastic tourniquet and those of SMAT by superior mesenteric artery (SMA) clamping. MVPs (mm Hg) were found to significantly increase with all degrees of PV occlusion (P < 0.01, Student's t test) and to significantly decrease after SMA occlusion (P < 0.01). Portography clearly demonstrated all degrees of PV stenosis after PV occlusion and stasis of contrast medium during SMA occlusion. The authors feel that this method enables rapid diagnosis of PVT and SMAT and may be useful in the monitoring of the therapy for these complications after small bowel transplantation.

Animals↗

Use of monoethylglycinexylidide as a liver function test in the liver transplant recipient.

The hepatic conversion of lignocaine to monoethylglycinexylidide (MEGX) has been used as a real time monitor of liver function in liver transplant recipients. Data are reported for the first 4 weeks after transplant in 50 consecutive orthotopic liver grafts in 47 adults. The MEGX concentration was significantly depressed by approximately 50% in those patients in whom there was a complicated clinical course (excluding steroid-sensitive rejection) after transplantation, compared with patients in whom major complications did not occur. The MEGX concentration in the recipients after transplant was independent of the donor MEGX concentration, but, in addition to the patient's clinical status, was strongly influenced by the recipients pretransplant biochemical profile, being inversely related to the pretransplant bilirubin concentration. MEGX concentrations < 25 micrograms/L in the first 36 hr after revascularization were predictive of greater morbidity and mortality.

Adolescent↗

Distribution of body water in patients with cirrhosis: the effect of liver transplantation.

We compared total body water and intracellular-extracellular distribution of body water between male patients with mild liver disease without ascites (n = 9), male patients with severe liver disease and gross ascites (n = 6) and a group of age-, sex-, height- and weight- matched controls (n = 6). In addition, we documented the effects of liver transplantation on intracellular, extracellular and total body water in 12 patients (6 men and 6 women) by means of deuterium oxide dilution and whole-body potassium counting. We saw no significant difference in total body water between the healthy controls, patients without ascites and patients with ascites (46.5 +/- 9.2 kg, 45.4 +/- 6.6 kg and 50.4 +/- 5.1 kg, respectively), although, as expected, extracellular water was increased in patients with ascites compared with healthy controls and cirrhotic patients without ascites (36.9 +/- 6.5 kg vs. 25.4 +/- 4.4 kg, p = 0.005; and 36.9 +/- 6.5 kg vs. 27.0 +/- 5.3 kg, p = 0.002, respectively). We found no difference between non-ascitic patients and healthy controls (25.4 +/- 4.4 kg vs. 27.0 +/- 5.3 kg). However, intracellular water was significantly reduced in patients with severe liver disease compared with that in controls (13.6 +/- 3.3 kg vs. 21.5 +/- 4.2 kg, p = 0.005) or patients without ascites (13.6 +/- 3.3 kg vs. 18.3 +/- 2.9 kg, p = 0.01). The reduction of intracellular water appears to be due to loss of body cell mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Undifferentiated (embryonal) sarcoma of the liver. Pathologic findings and long-term survival after complete surgical resection.

Undifferentiated (embryonal) sarcoma of liver is a rare tumor with a reputed poor prognosis. Four patients with this tumor are reported, of whom three were alive without recurrence 1.5, 2.5, and 12 years after initial complete surgical resection, and two of whom received no adjuvant therapy. The fourth patient, in whom complete surgical resection of tumor was not achieved, died with recurrent tumor at 13 months. The latter tumor differed histologically and consisted mainly of closely packed smaller undifferentiated cells with a higher mitotic and apoptotic rate. Eosinophilic globules, characteristic of embryonal sarcoma, were found in some cases to contain condensed nuclear chromatin, evidence of origin from tumor cells dying by apoptosis. One tumor mainly contained large cysts lined by biliary-type epithelium; this suggested an origin from a multipotent precursor cell able to differentiate along both stromal and epithelial lines.

Adolescent↗

Glomerular abnormalities in children undergoing orthotopic liver transplantation.

A prospective study of renal function was undertaken on an unselected group of 8 children with chronic progressive liver disease on whom a renal biopsy was performed subsequently at the time of orthotopic liver transplantation. Two patients had abnormal urinalyses and 2 elevated urinary albumin/creatinine ratios. The remainder had no clinical evidence of renal dysfunction. All had normal serum creatinine concentrations. Glomerular abnormalities were present in all renal biopsies and were of two types: hepatic glomerulosclerosis (n = 5) and minor glomerular abnormalities (n = 3). IgM immunofluorescence was present in all biopsies and IgA in 6. Elevated serum immunoglobulin levels were observed in all patients, with IgM elevation in 6, IgA in 4 and IgG in 6. C3 and/or C4 were reduced in 5 patients and increased circulating immune complexes containing IgM were noted in 4. The clinical significance of these cirrhosis-associated glomerular abnormalities can only be established by long-term follow-up studies after orthotopic liver transplantation.

Albuminuria↗

Universal occurrence of glomerular abnormalities in patients receiving liver transplants.

We conducted a prospective study of renal histology and function in 18 consecutive nonalcoholic patients who underwent orthotopic liver transplantation (OLT). Despite well-preserved renal function, all patients had abnormal renal biopsies. Four patterns of glomerular injury were identified: minor glomerular abnormalities (eight patients), hepatic glomerulosclerosis (seven), membranoproliferative glomerulonephritis (one), and IgA nephropathy (one). In one patient there was insufficient tissue to allow classification. There was a trend toward lower plasma bilirubin and higher plasma albumin in patients with minor glomerular abnormalities than in the group of patients with more severe forms of glomerular injury (29 v 82 mumol/L, 35.5 v 30 g/L; P = 0.1, 0.1 greater than P greater than 0.05, respectively). Glomerular changes persisted in the three patients who died within 7 weeks post-OLT. IgM immunofluorescence was present in all biopsies and IgA in 11. IgM-containing circulating immune complexes occurred in five patients, suggesting a pathogenic role for IgM immune complex deposition. The significance of cirrhosis-associated glomerular abnormalities is not yet known. They may contribute to the hepatorenal syndrome and the renal dysfunction that occurs in up to 94% of patients post-OLT.

Adolescent↗

Nutritional support in children with end-stage liver disease: a randomized crossover trial of a branched-chain amino acid supplement.

Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched-chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA-enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD, and are deserving of wider application and study.

Albumins↗

The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation.

To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction, 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 +/- 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients.

Amino Acids↗