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Biomedical subjects

A Duncan

Publications and source records attributed to A Duncan.

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

Chemotherapy-induced hemolytic uremic syndrome: description of a potential animal model.

Hemolytic uremic syndrome (HUS) is an uncommon complication of chemotherapy that contributes to the morbidity of oncology and bone marrow transplant patients. The pathogenesis is not well understood and no established clinical animal model exists. We studied four rhesus monkeys (RM) that developed fatal HUS following high-dose chemotherapy. Microangiopathic hemolytic anemia (pre-Hct 40% and day 5-8 Hct 31% (P < .05), increased BUN (168 mg/dl), creatinine (8.2 mg/dl), and lactate dehydrogenase (1458 IU/L) (mean day 5-8 measurements) were observed. Platelets counts decreased to 39 +/- 15 x 10(9)/l from a mean of 397 +/- 31 x 10(9)/L (P < .0001). vWF, ATIII, thrombin:anti-thrombin complex (T:AT) and prothrombin fragment F1.2 levels were not different from a control group (N = 2). The data presented describe chemotherapy-induced HUS with typical clinical and laboratory features which may provide an animal model for the study of this important syndrome.

Animals↗
PubMed1995

Iatrogenic profound hypoalphalipoproteinaemia: an unrecognised cause of very low HDL cholesterol.

A significant reduction in plasma high density lipoprotein (HDL) cholesterol is a recognised consequence of treatment with probucol. By contrast, fibrate therapy in general has the opposite effect. We report two cases where the combination of probucol and a fibrate led to profoundly reduced plasma levels of HDL cholesterol associated with very low levels of apolipoprotein A-I (apoA-I). In the first, bezafibrate was added to probucol, and in the second, probucol added to a combination of simvastatin and fenofibrate. In both cases, plasma levels of HDL and apoA-I returned towards normal after discontinuation of one or both drugs, indicating that the reduction was reversible.

Adult↗
PubMed1995

Variations in the radiological management of intussusception: results of a postal survey.

A survey of the radiological reduction of intussusception in a selection of British hospitals was performed using a questionnaire. Replies were received from radiologists working in 51 district general hospitals and 25 teaching hospitals or specialist paediatric institutions. Most district general hospitals still use barium as the sole method of reduction of intussusception. Most teaching hospitals and specialist paediatric units have changed to a pneumatic method. The contra-indications, details of patient preparation and technical details of each method varied considerably.

Air Pressure↗
PubMed1995

Percutaneous dilatational tracheostomy: an alternative approach to surgical tracheostomy.

Percutaneous dilatational tracheostomy (PDT) offers a nonoperative alternative to patients needing an elective tracheostomy. The technique associated with PDT is essentially a progressive dilatation using blunt-tipped dilators for the placement of a tracheostomy tube. We retrospectively compared patient charges and operating time for 18 PDTs and 18 surgical tracheostomies. Our analysis suggests that percutaneous dilatational tracheostomy is a cost-effective alternative to the open procedure for elective tracheostomy.

Fees and Charges↗
PubMed1995

The role of diuretics in the aetiology of idiopathic oedema.

The hypothesis that diuretic use and abuse and other purging behaviours cause idiopathic oedema was investigated in 102 patients. Of 91 symptomatic idiopathic oedema patients tested at referral, 16 (17.6%) had diuretic and four (4.4%) laxative in their urine. None had grossly disturbed serum urea and electrolytes. Examination of primary care records from 41 idiopathic oedema patients who denied current diuretic consumption, and denied or were uncertain about past consumption, showed that 20 had not been prescribed diuretics by their general practitioners at any time; a further 18 had not been prescribed diuretics for between seven months and 12 years before referral. The absence of evidence of plasma volume depletion (as judged by similar concentrations of mean serum urea, creatinine, total protein and albumin in patient and age-matched control groups) suggests that neither systematic diuretic and laxative use or abuse, nor episodic overeating and vomiting were responsible for symptoms of idiopathic oedema in our patients. Idiopathic oedema has a strong genetic basis, and correction of major and minor risk factors for this condition leads to substantial amelioration of symptoms in most cases.

Adult↗
PubMed1994

Urinary hydroxypyridinium crosslinks of collagen in population-based screening for overt vertebral osteoporosis: results of a pilot study.

The urinary pyridinium crosslinks pyridinoline (PYD) and deoxypyridinoline (DPD) have been shown to provide valid indices of bone resorption. At present, both crosslink components are determined by reversed-phase HPLC, a time-consuming method precluding the use of these markers for routine purposes. Therefore, efforts have been made to develop simple immunoassays for the rapid measurement of urinary crosslinks, and their application to large-scale osteoporosis screening has been proposed. To evaluate the applicability and diagnostic validity of pyridinium crosslink measurements for screening purposes, urinary concentrations of total and free PYD and DPD were determined by HPLC and immunoassay technique (ELISA) in a sample of 269 individuals (male to female ratio = 130:139; age 50-81 years) recruited at random within a population survey of vertebral osteoporosis. On a molar basis, ELISA measures of crosslink-related epitopes were highly correlated with both total and free PYD and DPD as determined by HPLC (r > 0.82, p < 0.001). Age-specific means for creatinine-corrected total and free pyridinium crosslinks were significantly higher in females than in males (p < 0.001). In both sexes, neither age nor anthropometric variables (weight, height, and body mass index) showed a linear effect on the urinary crosslink/creatinine ratio. On average, 50% of the total amount of urinary crosslinks were present in free form. For both PYD and DPD, this proportion was significantly higher in women than in men (p < 0.05), but no change was observed with age or anthropometric measures. The excretion of pyridinium crosslinks was higher in osteoporotic (n = 18) than in nonosteoporotic individuals (n = 208) from the same population.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Human mitochondrial HMG CoA synthase: liver cDNA and partial genomic cloning, chromosome mapping to 1p12-p13, and possible role in vertebrate evolution.

Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase (mHS) is the first enzyme of ketogenesis, whereas the cytoplasmic HS isozyme (cHS) mediates an early step in cholesterol synthesis. We here report the sequence of human and mouse liver mHS cDNAs, the sequence of a HS-like cDNA from Caenorhabditis elegans, the structure of a partial human mHS genomic clone, and the mapping of the human mHS gene to chromosome 1p12-p13. The nucleotide sequence of the human mHS cDNA encodes a mature mHS peptide of 471 residues, with a mean amino acid identity of 66.5% with cHS from mammals and chicken. Comparative analysis of all known mHS and cHS protein and DNA sequences shows a high degree of conservation near the N-terminus that decreases progressively toward the C-terminus and suggests that the two isozymes arose from a common ancestor gene 400-900 million years ago. Comparison of the gene structure of mHS and cHS is also consistent with a recent duplication event. We hypothesize that the physiologic result of the HS gene duplication was the appearance of HS within the mitochondria around the time of emergence of early vertebrates, which linked preexisting pathways of beta oxidation and leucine catabolism and created the HMG CoA pathway of ketogenesis, thus providing a lipid-derived energy source for the vertebrate brain.

Amino Acid Sequence↗
PubMed1994

Astrocyte associations with nodes of Ranvier: ultrastructural analysis of HRP-filled astrocytes in the mouse optic nerve.

Astrocytes are implicated in the function of nodes of Ranvier because their perinodal processes form contacts with the axonal membrane at nodes. We have filled astrocytes iontophoretically with horseradish peroxidase in the intact mouse optic nerve to resolve the precise relationship between perinodal processes and astrocyte three dimensional structure. We confirm that nodal contacts were formed either by single processes which almost completely enveloped nodes, or by delicate, finger-like projections from larger processes which made discrete nodal contacts. A single perinodal process can form multiple contacts with a node and nodes were contacted by processes from more than one astrocyte. Perinodal processes emanated from larger processes, which terminated as end-feet on blood vessels and at the pia, as well as collateral branches which subsequently ended at nodes; these latter may specifically subserve nodes. Perinodal contacts were also formed directly by the soma and cytoplasmic expansions of the cell body. Both primary processes and collateral branches formed multiple associations with nodes which often appeared in clusters. Thus, all astrocytes formed multiple contacts with nodes, blood vessels and the subpial glia limitans. We conclude that perinodal processes are not formed by a specialized astrocyte in the mouse optic nerve.

Animals↗
PubMed1994

Myelin repair by Schwann cells in the regenerating goldfish visual pathway: regional patterns revealed by X-irradiation.

In the regenerating goldfish optic nerves, Schwann cells of unknown origin reliably infiltrate the lesion site forming a band of peripheral-type myelinating tissue by 1-2 months, sharply demarcated from the adjacent new CNS myelin. To investigate this effect, we have interfered with cell proliferation by locally X-irradiating the fish visual pathway 24h after the lesion. As assayed by immunohistochemistry and EM, irradiation retards until 6 months formation of new myelin by Schwann cells at the lesion site, and virtually abolishes oligodendrocyte myelination distally, but has little or no effect on nerve fibre regrowth. Optic nerve astrocyte processes normally fail to re-infiltrate the lesion, but re-occupy it after irradiation, suggesting that they are normally excluded by early cell proliferation at this site. Moreover, scattered myelinating Schwann cells also appear in the oligodendrocyte-depleted distal optic nerve after irradiation, although only as far as the optic tract. Optic nerve reticular astrocytes differ in various ways from radial glia elsewhere in the fish CNS, and our observations suggest that they may be more permissive to Schwann cell invasion of CNS tissue.

Animals↗
PubMed1994

A retrospective assessment of the clinical value of jejunal disaccharidase analysis.

BACKGROUND: The measurement of jejunal disaccharidases is used by several gastroenterologists when investigating suspected small-bowel disease. The clinical value of this analysis is assessed. METHOD: The histology and disaccharidase results in 1585 jejunal biopsy specimens were reviewed retrospectively. RESULTS: Disaccharidase and histology results concurred in most cases (72%). However, disaccharidases were an insensitive indicator of small-bowel disease: low levels were found in only 65% of coeliac patients with villous atrophy, 15% of patients with giardiasis, and 6% of patients with villous atrophy associated with non-coeliac histology. Low disaccharidase levels were sometimes found in patients with normal histology (1.6%) and when biopsy specimens were unwittingly taken from non-jejunal sites (1.4%). Isolated low lactase activities were found in 3.2%. Usually this finding was not clinically relevant because patients had no symptoms of lactose intolerance (38%), had another diagnosis that responded to appropriate treatment (8%), or had no response to a low-lactose diet (14%). In 16 patients sucrase activities were markedly low, and this investigation proved central to the diagnosis of sucrase-alpha-dextrinase deficiency, which was subsequently confirmed in 9. CONCLUSION: Jejunal disaccharidases are clinically useful only in the diagnosis of sucrase-alpha-dextrinase deficiency. We recommend that their measurement be reserved for the investigation of patients suspected of having this condition.

Adult↗
PubMed1994

Effectiveness of radon relative to acute 60Co gamma-rays for induction of micronuclei in vitro and in vivo.

Because radon and its progeny (referred to collectively here as radon) emit alpha particles with a wide range of energies, as well as beta particles and gamma-rays, it is important to quantitate the relationship between initial damage induced by radon and that by acute low-LET radiation. We have evaluated dose-response relationships for induction of micronuclei both in vivo and in vitro following exposure to radon or 60Co. To determine if isolation procedures altered the cells' responsiveness to 60Co gamma-ray exposures, animals were exposed before cell isolation, or cells were isolated and then exposed. The data were described by linear dose-response functions and were not significantly different when the radiation exposure was in vivo or in vitro (respectively micronuclei/1000 binucleated cells = 1.6 +/- 6.5 + 62 +/- 2.7 D; micronuclei/1000 binucleated cells = 15.4 +/- 26.0 + 54.6 +/- 11.4 D, where D is in Gy). Primary rat lung fibroblasts (RLF) or Chinese hamster ovary (CHO-K1) cells were exposed in vitro to either radon or 60Co gamma-rays. Radon was 10.9 +/- 2.6 and 12.5 +/- 2.4 times as effective per Gy of radiation dose in producing micronuclei as was 60Co in RLF and CHO-K1 cells respectively. To determine the relative biological effectiveness of in vivo radon exposure, animals were exposed to either radon or 60Co, and lung fibroblasts were isolated and evaluated for radiation-induced micronuclei. In vivo radon exposure was 10.6 +/- 1.0 times as effective as acute whole-body 60Co exposure in producing micronuclei in lung fibroblasts. Different cell lines and exposure conditions resulted in similar effectiveness factors. Such ratios help evaluate the biological damage, hazard and risk associated with radon inhalation.

Animals↗
PubMed1994

Intestinal permeability in patients with Crohn's disease and their first-degree relatives.

OBJECTIVE: To measure small intestinal permeability in a group of patients with Crohn's disease in clinical remission and their apparently healthy first-degree relatives. METHODS: Administration of 51Cr-labeled EDTA and subsequent measurement of its excretion in a 24-h urine collection. RESULTS: Excretion of 51Cr-EDTA was not elevated in either the patients or in first-degree relatives. CONCLUSION: Intestinal permeability to 51Cr-EDTA is not raised in patients with Crohn's disease in clinical remission or in their healthy first-degree relatives.

Chromium Radioisotopes↗
PubMed1993

3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL): cloning and characterization of a mouse liver HL cDNA and subchromosomal mapping of the human and mouse HL genes.

3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL) is a homodimeric mitochondrial matrix enzyme that catalyzes the last step of ketogenesis. Using a human HL cDNA as a probe, we isolated a 1.4-kb mouse HL cDNA (HLM) from a mouse liver library and extended the sequence in the 5' direction, using RACE PCR to include the complete coding sequence. The nucleotide sequence of the mouse HL coding region is 85.7% identical to human HL, and 52.6% to Ps. mevalonii HL. Peptide identities of 87.4% and 54.3% respectively were observed. Southern analysis of 29 strains of laboratory mice and of Mus spretus revealed a total of about 25 kb of hybridizing fragments and three polymorphic fragments in both EcoRI and Hin-dIII digestions. The mouse HL locus (Hmgcl) was localized on Chromosome (Chr) 4: Pmv-19-12.6 +/- 3.6 cM-Hmgcl-7.3 +/- 2.3 cM-Xmv-8-1.5 +/- 1.0 cM-Gpd-1. The human HL locus (HMGCL) was mapped to distal Chr 1p by analysis of a human-hamster hybrid cell panel and by in situ hybridization.

Amino Acid Sequence↗