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Biomedical subjects

D A Kelly

Publications and source records attributed to D A Kelly.

At least 91 records · Page 5Linked to original sources
PubMed1997

Clinical features and prognosis of children assessed for isolated small bowel or combined small bowel and liver transplantation.

The hepatic histology and clinical status of 37 children on long-term parenteral nutrition (PN) referred for consideration of small bowel transplantation were determined. Seventy five percent of the children had splenomegaly and plasma bilirubin level of greater than 100 mumol/L. All of 21 children who underwent liver biopsy, had increased fibrosis, but only half had established cirrhosis. Thirty-one children were considered to be in need of transplantation (combined liver and bowel transplant, 29; isolated bowel transplant, 2), but only 13 were stable enough to be placed on the transplant list. Seven out of the thirteen children waiting have died because of lack of size-matched organs, and the overall mortality rate of the 37 children was 70%. The main risk factors for death within 6 months were bilirubin level of greater than 100 mumol/L, splenomegaly, and cirrhosis (P = .01). The natural history of PN-associated liver disease is that of progressive liver failure and death 6 to 12 months after onset of cholestasis, defined as bilirubin level of greater than 100 mumol/L. The development of cirrhosis occurs after the onset of jaundice, so early referral may also permit some children to be offered isolated bowel transplantation, which has better outcome than combined liver and bowel transplantation.

Adolescent↗
PubMed1997

Nutritional factors affecting growth before and after liver transplantation.

Malnutrition is present in approximately 60% of children at the time of liver transplantation. The pathogenesis of malnutrition is complex and includes reduced calorie intake, fat malabsorption, abnormal nitrogen metabolism, and increased energy expenditure leading to increased calorie requirements. As nutritional status at transplantation is a significant factor in both morbidity and mortality post liver transplantation, intensive nutritional support pre-transplant is vital and may be achieved with a modular feed providing 120-150% estimated average requirement (EAR). Approximately 80% of children who survive liver transplantation will achieve normal growth and nutritional status within 12 months post-transplant. Significant factors responsible for growth failure post-transplant include pre-operative nutritional status (height SDS score <-2), continued glucocorticoid administration, recurrent hepatic dysfunction or chronic rejection and reduced calorie intake due to behavioural feeding problems. Effective future strategies include intensive pre- and post-operative nutritional support and early reduction of glucocorticoid administration.

Female↗
PubMed1997

Posttransplant growth failure in children.

As malnutrition is inevitable in 60% of children with end-stage liver disease, reversal of malnutrition is one of the key aims of liver transplantation. Although good catch-up growth may be achieved in the majority of survivors, persistent growth failure has been noted in 15% to 20% of children. The origin of posttransplant growth failure is complex. It is related to the degree of preoperative malnutrition because children who are severely stunted (height SDS <-1) pretransplant never achieve completely normal growth. Glucocorticoid administration is clearly a major factor because good catch-up growth is achieved on alternate-day steroid regimes or when steroids are discontinued. Significant hepatic dysfunction such as chronic rejection or the development of lymphoproliferative disease that requires alteration in immunosuppressive regimes or prolonged hospitalization may also inhibit linear growth. A less well recognized factor is the development of behavioral feeding problems either before or after transplantation, which reduces adequate oral intake and may be a significant cause of growth failure long term. Important strategies to prevent posttransplant growth failure include early referral for liver transplantation before the development of malnutrition, a multidisciplinary approach to pre- and postoperative nutritional intervention, and the early withdrawal of steroid therapy after transplantation.

Child↗
PubMed1996

Transplantation for end stage liver disease related to alpha 1 antitrypsin.

Alpha 1 antitrypsin deficiency (AT) is an autosomal recessive disease associated with chronic liver disease in adults and children and emphysema in adults. The disease is one of the most common inherited disorders of the Caucasian population of North Europe and North America and is the most common genetic reason for pediatric orthotopic liver transplantation (OLTx), although it is a rare indication in adults. The natural history of the disease is unpredictable and the pathogenesis of the liver injury unclear. Thirty-five patients with histologically apparent alpha 1 AT accumulation in the liver (22 adults, 13 children) have been transplanted in this center. Clinical features were correlated with the pretransplant phenotype, serum alpha 1 antitrypsin levels and potential precipitating factors. All children were PiZZ homozygotes, most of whom had presented with neonatal hepatitis. The majority of adult patients were heterozygotes presenting with portal hypertension and liver cirrhosis. Current one-year posttransplant survival figures are 73% for adults and 87.5% for children. Replacement of the cirrhotic liver results in acquisition of the donor phenotype, a rise in serum levels of alpha 1 antitrypsin, and apparent prevention of associated disease.

Adult↗
PubMed1996

Unresectable hepatic tumors in childhood and the role of liver transplantation.

Liver transplantation has been performed in five children with unresectable hepatic tumors who did not have extrahepatic metastases at the time of surgery. Two of the children had hepatoblastomas, one had an infantile hemangioendothelioma, and two had a hepatoma. The two children who had hepatoblastoma are well (37 and 25 months posttransplant) and have no evidence of recurrence. The child with infantile hemangioendothelioma had a successful operation, with good quality of life, but died of tumor recurrence 41 months after transplantation. Both children with hepatomas died, one of graft failure owing to chronic rejection and the other of tumor recurrence 5 months posttransplant. These results suggest that liver transplantation may be successful in children with unresectable hepatic tumors without extrahepatic spread and should be considered particularly for the treatment of hepatoblastoma.

Carcinoma, Hepatocellular↗
PubMed1996

Hepatitis C infection after blood product transfusion.

HCV infection has been demonstrated in multiply transfused children who received blood products or transplanted organs before universal screening in 1990. The risk of active infection is related to the number of transfusions or pooled blood products. Accurate diagnosis of infection is dependent on utilisation of third generation RIBA and identification of HCV RNA by RT-PCR. The natural history of HCV in childhood is undetermined and prospective long term studies should be undertaken. It is likely that about develop chronic hepatitis with progression at some time to cirrhosis and have an increased risk of developing liver cancer. Treatment with interferon alfa may be effective in up to 50% of children and only those children with documented infection with HCV RNA should be selected for treatment. In order to answer important questions about natural history, outcome, and the necessity and efficacy of treatment response, treatment for these children should only be as part of scientifically conducted studies on a multicentre basis.

Child↗
PubMed1996

Risk factors for liver rejection: evidence to suggest enhanced allograft tolerance in infancy.

After liver transplantation, a relatively low intensity immunosuppressive regimen is employed in our unit: after initial triple therapy (prednisolone, azathioprine, cyclosporin), prednisolone is discontinued at three months and azathioprine at one year. A retrospective study was therefore performed to determine the incidence of rejection, and to identify risk factors for rejection in our patient population. Over a 10 year period, 135 transplants were performed on 109 children. Thirty four (25%) were on infants less than 1 year old. Incidences of acute rejection and irreversible chronic rejection were calculated for grafts surviving more than one and four weeks respectively. Acute rejection occurred in 51 of 101 allografts (50%), and irreversible chronic rejection in 11 of 91 allografts (12%). The immunosuppression strategy was not associated with an increased incidence of rejection. Acute rejection occurred in only eight of 28 allografts (29%) in those transplanted during their first year, compared with 43 of 73 (59%) in older children. Logistic and Cox regression analysis supported age at transplantation as a significant risk factor for acute rejection. Irreversible chronic rejection did not occur in any of 24 grafts in patients transplanted before one year, compared with 11 of 67 (16%) in older recipients. This suggests possible enhanced allograft tolerance with transplantation during the first year of life. This unexpected and potentially important finding now requires confirmation in other large patient series, with blind interpretation of post-transplant liver biopsies.

Adolescent↗
PubMed1996

Effect of vitamin E deprivation and exercise training on induction of HSP70.

To investigate the effect of dietary vitamin E deprivation and chronic exercise on the relative content of selected isoforms of the heat-shock protein 70 (HSP70) family in rat hindlimb muscle, vitamin E was withheld for 16 wk from female rats that underwent treadmill run training during the final 8 wk. As indicated by increased (P < 0.05) content of the stress-inducible isoform (HSP72), training did stress the exercising muscles. However, vitamin E deficiency did not alter HSP72 content in nontrained rats and was associated with a lesser induction (P < 0.01) in some muscles of trained animals. The constitutive isoform, which exhibited similar levels in muscles of varying fiber types, was demonstrated to be largely refractory to exercise, with an equivocal response to vitamin E deprivation. HSP72 content was correlated to type I myosin heavy chain (MHC-I) content but only in muscles of sedentary normal-diet rats. After training, HSP72 content in a muscle essentially devoid of MHC-I (superficial vastus lateralis) reached levels comparable to those in a muscle high in MHC-I (soleus).

Animals↗
PubMed1995

ECG and echocardiographic diagnosis of pulmonary thromboembolism associated with central venous lines.

The aim was to establish the prevalence of pulmonary embolism in 21 children (median age 12 months; range 5-132 months) with central venous lines in situ > 3 months (median 10 months; range 3-47). Twelve-lead electrocardiograms (ECGs) and echocardiograms were analysed in a retrospective study using ECG and echocardiographic criteria for pulmonary embolism-previously established and validated in adult patients- and standard paediatric ECG values as control data. Patients were scored as having definite (n = 7), probable (n = 5), or no pulmonary embolism (n = 9). Overall 57% of ECGs showed abnormalities compatible with pulmonary embolism. In two patients, serial ECGs obtained during an acute cardiorespiratory illness showed cumulative changes diagnostic of pulmonary embolism. Eight of 12 patients with abnormal ECGs had echocardiography; in seven of these (88%) the right ventricular end diastolic diameter was > 2SD above the mean value for age. Twelve of the patients included in this study have died; two died following an acute respiratory illness. There was postmortem evidence of pulmonary thromboembolism in both of the two children for whom necropsy information was available. The data suggest that pulmonary embolism is common in children who have central venous lines in situ for > 3 months. Serial studies are of value in some patients. Pulmonary embolism may compromise the long term survival of children with small bowel failure and preclude consideration for liver and small bowel transplantation.

Catheterization, Central Venous↗
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

Characterization of biliary epithelial cells isolated from needle biopsies of human liver in the presence of hepatocyte growth factor.

Current methods for the isolation of intrahepatic biliary epithelial cells from human liver rely upon relatively large segments of tissue, thereby limiting studies to cells isolated from patients with end-stage disease. To investigate a greater range of diseases and those at an earlier stage, we have developed a method to isolate biliary epithelial cells from biopsy-sized fragments of human liver. Tissue explants are cultured for > 4 weeks, and, in approximately 50% of samples incubated with medium containing hepatocyte growth factor, biliary epithelial cells begin to migrate from the fragments and proliferate. With time they form confluent pavements of cells that express cytokeratin 19 and gamma-glutamyl transpeptidase and are negative for markers of non-biliary cell phenotype. After subculturing, cells can be expanded, yielding substantial numbers for subsequent study in vitro. Cells can be isolated with a similar degree of success from adult normal liver, from a variety of liver diseases, and from post-transplant liver biopsies. Overall, pediatric tissue yielded cells less frequently than adult tissue. This novel technique is likely to have a major impact on the study of biliary pathophysiology, as small fragments of tissue removed from biopsies taken for diagnostic purposes can be used.

Adolescent↗
PubMed1995

Bone fractures in children undergoing orthotopic liver transplantation.

This retrospective study documents the incidence and distribution of fractures in 117 children with end-stage liver disease who underwent orthotopic liver transplantation (OLT) over a 6-year period (1987-1993). Both the pre- and post-OLT phases were included. Nineteen children (16.2 %) sustained a total of 69 fractures. Age at time of fracture ranged from 3 months to 9 years 8 months (median 13.5 months). There was no documented trauma in 14/19 cases. Metabolic bone disease, assessed qualitatively on plain radiographs, was present in 17/19 children at the time of fracture. This took the form of rickets (n = 3), osteopenia (n = 12) and osteosclerosis (n = 2). Potential risk factors including pre-existing metabolic bone disease, drugs and immobilization were assessed. The findings emphasise the need for clinical and radiological awareness of the fracture risk, particularly during the peri-transplant period when this risk may be greatest.

Bone Diseases, Metabolic↗
PubMed1994

Novel application of a point mutation assay: evidence for transmission of hepatitis B viruses with precore mutations and their detection in infants with fulminant hepatitis B.

Mutations of the precore region of hepatitis B virus (HBV) genome have been associated with fulminant and severe chronic hepatitis. However uncertainty remains about the clinical significance and transmissibility of these mutant strains. A point mutation assay (PMA) was developed to identify qualitatively and quantitatively mutations affecting precore amino acids 1 and 28. We have analysed serum samples from six mother-infant pairs where perinatal transmission of HBV has occurred and where the mothers were HBV carriers without detectable serum HBeAg. In three cases fulminant hepatitis developed in the infant, in two cases acute hepatitis resolved, and in one case the infant was immunised and did not become infected. We also examined serum from a healthcare worker, an anti-HBe-seropositive HBV carrier, believed to have transmitted HBV infection to a patient. The PMA results were confirmed in all cases by direct sequencing of polymerase chain reaction (PCR) products using nested and double-nested PCR with primers to the precore and X region. Precore aa28 mutant-type virus was detected in the serum of one mother at the time of delivery of three of her children, two of whom developed fulminant hepatitis. Another mother of an infant with fulminant hepatitis had no precore mutations. In one mother-infant pair a mixed viral population was found; the acute hepatitis B in the infant resolved. The HBV sequence from the healthcare worker was also of aa28 mutant type. No mutations of aa1 were detected in any of the specimens. The study supports the association of precore mutations with some cases of transmission of HBV infection from HBeAg-negative mothers to their infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗