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Biomedical subjects

D A Kelly

Publications and source records attributed to D A Kelly.

At least 109 records · Page 6Linked to original sources
PubMed1994

Do H2 receptor antagonists have a therapeutic role in childhood?

Studies of the therapeutic efficacy and indications for the use of histamine (H2)-receptor antagonists (H2RAs) in children are reviewed. In adequate dosages, both ranitidine and cimetidine reduce acid output and increase intragastric pH, and H2RAs have been shown to be effective in the treatment of acid-peptic disease. Ranitidine is a more potent drug with a longer duration of action than cimetidine and thus requires less frequent administration. Dosage requirements vary according to age and clinical condition, and children require a relatively higher drug dosage (mg/kg) than adults. There is insufficient information on the long-term paediatric use of famotidine to validate its use in children, and the endocrinological side effects associated with cimetidine therapy in adults essentially preclude its long-term use in children. It is suggested that ranitidine administration is safe and effective in children with acid-peptic disease and should be considered as first-line treatment for children with severe oesophagitis or peptic ulceration and for the prophylaxis of stress ulceration and aspiration pneumonitis.

Adolescent↗
PubMed1994

Organ transplantation for inherited metabolic disease.

Liver transplantation for inherited metabolic disease is a therapeutic reality in the 1990s. Careful patient selection and timing and choice of operative procedure should greatly improve the quality of life and long term survival for those children with life threatening metabolic disease. The rapid expansion of molecular genetics and the development of effective gene therapy may well displace liver transplantation as appropriate treatment of these disorders in the future.

Child↗
PubMed1994

Novel splice, missense, and nonsense mutations in the fumarylacetoacetase gene causing tyrosinemia type 1.

In six unrelated patients with hereditary tyrosinemia type 1 (HT1), three different disease-causing mutations were found by DNA sequencing. Two Pakistani patients, with acute and intermediate forms of HT1, were homozygous for a G192-->T mutation in the last nucleotide of exon 2. This caused aberrant splicing with partial intron 2 retention and premature termination. Three Turkish patients with chronic and intermediate forms of HT1 were homozygous for an A698-->T mutation substituting aspartic acid 233 with valine. A Norwegian patient with an intermediate clinical phenotype was heterozygous for G786-->A, introducing a TGA stop codon for Trp262 (W262X). Site-directed mutagenesis and expression in a rabbit reticulocyte lysate system demonstrated that the nonsense and missense mutations abolished fumarylacetoacetase activity and gave reduced amounts of a truncated and a full-length protein, respectively. Simple tests were established to identify the three mutations by restriction digestion of PCR-amplified genomic DNA. Among 30 additional HT1 patients investigated, 2 were found to be homozygous and 1 heterozygous for G192-->T. Two other patients were homozygous and one was heterozygous for W262X.

Alternative Splicing↗
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↗
PubMed1993

Niemann-Pick disease type C: diagnosis and outcome in children, with particular reference to liver disease.

The records of 52 children with Niemann-Pick disease type C were reviewed to establish whether the disease process and outcome varied with the initial clinical pattern; 34 children (65%) had cholestatic liver disease and hepatosplenomegaly in infancy; 18 were seen at a mean age of 4 years with splenomegaly or neurologic disease or both. Of the 34 children with early cholestatic liver disease, three died in the neonatal period; cholestasis and hepatomegaly subsided in the remaining 31 children, although splenomegaly persisted. Of these 31 children, 15 had persistent liver disease with elevated aminotransferase values. Serial liver biopsy specimens showed that 3 of the 15 children had normal architecture and 12 had hepatic fibrosis, with progression to cirrhosis in 5. No other significant morbidity or additional deaths were associated with the liver disease. The clinical importance of persistent liver disease was overshadowed by the subsequent development of severe neurologic disease. There was no difference in the age at onset of the disease (mean, 4.5 years) or in the pattern of neurologic disease, including supranuclear ophthalmoplegia, whether or not the child had early liver disease. Overt neurologic disease has not yet developed in seven surviving children with liver disease at onset. Sixty-seven percent of children died during the study; the main cause of death was bronchopneumonia. We conclude that the diagnosis of Niemann-Pick disease type C should be considered in patients with unexplained neonatal hepatitis, especially if splenomegaly is a persistent feature. Because liver biopsy specimens may not demonstrate storage cells, bone marrow aspiration to detect the characteristic storage cells is recommended in such patients.

Age Factors↗
PubMed1993

New method for determining faecal fat excretion in infancy.

Collecting complete, timed stool samples for the estimation of faecal fat from infants wearing nappies is difficult. A gravimetric method has been adapted by applying a chloroform/methanol homophasic solvent system to extract lipids from whole soiled nappies. In a study of 22 collections in six infants, no stools were lost and the recovery of lipids was 96%, with results similar to a reference titrimetric method. In addition to total fat, individual lipids were measured using gas-liquid chromatography. The method simplifies stool collection and analysis, is aesthetically more acceptable, and leads to reduced microbial hazards. It also allows the detailed study of excreted lipid species enabling the coefficient of absorption of dietary lipids of various chain lengths to be determined individually.

Chemistry, Clinical↗
PubMed1992

Hepatic transplantation in children using reduced size allografts.

The shortage of paediatric liver donors has led to the use of reduced size hepatic allografts. Between July 1987 and July 1990, 30 reduced size orthotopic liver transplantations were performed in 24 children aged between 3 months and 7 years. All patients were in advanced chronic or acute liver failure and were considered unlikely to survive for long enough for a size-matched donor to become available. The most common indication was biliary atresia. The median intraoperative blood loss was 75 (range 13-1015) ml kg-1. Nine patients have died and seven have undergone retransplantation, four successfully. Seven patients had portal vein hypoplasia with a high graft failure rate due to ischaemic infarction. There was significant morbidity from biliary tract complications, leading to further operations in four cases. The 1-year actuarial survival rate was 62 per cent.

Biliary Atresia↗
PubMed1991

Development of an in vivo 19F magnetic resonance method for measuring oxygen deficiency in tumors.

A 19F magnetic resonance spectroscopy (MRS) approach to measuring hypoxia in experimental tumors in rats at a field strength of 2.35 T has been investigated in a combined study of in situ and excised tumors. The detection of tumor hypoxia is based on the hypoxia marker approach which depends on the selective, covalent binding of a fluorinated 2-nitroimidazole to hypoxic cells. The 19F MRS measurement of in vivo hypoxia marker binding was made at a fixed postinjection time when unbound, circulating marker molecule concentrations had dropped below detectable levels. A correlation between 19F MRS and scintillation counting measures of tumor-bound, tritium-labeled hypoxia marker was observed. There was no correlation between integrated 19F MRS hypoxia marker signals and the in vivo 31P MRS parameters of hypoxia which have been developed to measure normal tissue ischemia. Radiolabeling studies and previous immunohistochemical studies with the fluorinated hypoxia marker support the conclusion that the 19F MRS approach has promise as a physically noninvasive guide to the use of hypoxia-dependent therapies at clinically usable MRS field strengths.

Adenocarcinoma↗
PubMed1990

Sleep apnea syndrome: symptomatology, associated features, and neurocognitive correlates.

This article reviews the essential features, types, prevalence, pathophysiology, and neuropsychological correlates associated with the sleep apnea syndrome. Persons who experience the intermittent hypoxia and fragmented sleep characteristic of the sleep apnea syndrome tend to exhibit moderate symptoms of diffuse cognitive dysfunction as well as multiple emotional and psychosocial sequela. It is concluded that more research is required in order to elucidate the relationship between the hypoxic parameters and neurocognitive deficits seen in the sleep apnea syndrome, and that neuropsychological assessment might represent a means whereby the effectiveness of various treatments for sleep apnea may be evaluated.

Brain↗
PubMed1989

Rise and fall of coeliac disease 1960-85.

A total of 192 children who presented with coeliac disease to Queen Elizabeth Hospital for Children from 1960-85 were reviewed in order to investigate the frequency and the age of presentation. There was a clear peak in the number of children presenting from 1971-5, and although the numbers declined subsequently they have remained at a level similar to numbers found before 1971. There was no difference in the mode of presentation but there was a definite increase in the age of presentation over the time period reviewed. Breast fed babies presented later than bottle fed babies (14 compared with 9 months) despite a similar age of gluten introduction. Similarly bottle fed babies and breast fed babies presented later after 1975 (10.5 compared with 7 months, and 18 compared with 9.5 months, respectively). Before 1975 the median age of gluten introduction was significantly less than that after 1975 (2 compared with 4 months) and the age of gluten introduction correlated with the age of presentation. It is concluded that breast feeding and the age of gluten introduction may influence the age of presentation of childhood coeliac disease but no clear reasons for the rise in incidence in the 1970s have been determined. It does not appear that the disease is declining, however, in recent years children have tended to present later in life.

Acute Disease↗
PubMed1988

Organ-specific control of glycolysis in anoxic turtles.

Control of glycolysis during anoxia was investigated in five organs (heart, brain, liver, and red and white skeletal muscles) of the freshwater turtle, Pseudemys scripta, after 1 or 5 h of submergence in N2-bubbled water. Lactate was produced as the metabolic end product, with distinct organ differences in the amount (net lactate accumulation was 2.4-fold higher in brain than white muscle) and rate (lactate production in liver dropped 16-fold after the 1st h) of lactate accumulation. ATP and total adenylate contents of all organs were reduced (by 15-32%) after 1 h of submergence, but energy charge was maintained; after 5 h, adenylate contents had fully recovered. Changes in the levels of hexose and triose phosphate intermediates of glycolysis indicated an activation of glycolysis within the 1st h of anoxia exposure in brain, heart, and skeletal muscles. By 5 h, however, these were reversed, and a glycolytic rate depression was indicated, consistent with the overall metabolic rate depression accompanying long-term anaerobiosis in the turtle. Crossover analysis indicated glycolytic control at the pyruvate kinase reaction in all organs during both glycolytic activation and metabolic depression; regulatory control at the phosphofructokinase locus was primarily important only during glycolytic activation in heart and red muscle. The same analysis indicated a very rapid glycolytic inhibition in liver occurring within the 1st h of anoxia exposure; this allows glycogenolysis to be directed toward glucose export yielding the fermentative fuel used by other organs during anoxia.

Adenosine Triphosphate↗