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Biomedical subjects

A Cooper

Publications and source records attributed to A Cooper.

At least 253 records · Page 14Linked to original sources

beta-mannosidase deficiency in a female infant with epileptic encephalopathy.

We report a female infant with an isolated deficiency of beta-mannosidase activity. At nine months of age dysmorphism was absent except for brachecephaly. There was moderate developmental delay and a startle response to sound. At 12 months there was a sudden onset of tonic-clonic seizures which were unresponsive to drug therapy, requiring paralysis and mechanical ventilation for control. The child died suddenly aged 15 months. beta-mannosidase activity was markedly reduced in white cells and cultured skin fibroblasts whilst other lysosomal enzymes were normal. The disaccharide ManGlcNAc was excreted in urine but urinary mucopolysaccharides were normal.

Abnormalities, Multiple↗

Effect of arterial carbon dioxide tension on the duration of action of atracurium.

The duration of action of atracurium was studied in two groups of patients. In group I (n = 15), patients' lungs were hyperventilated to a mean PaCO2 of 3.3 kPa and in group II (n = 15) lungs were ventilated to maintain a mean PaCO2 of 5.3 kPa. Anaesthesia was maintained using an infusion of propofol. The time taken to return to a T1 twitch height of 10% of control was measured following each incremental dose of atracurium 0.15 mg kg-1. It was found that the duration of action of atracurium was significantly (P less than 0.0005) shorter in the hypocapnic group.

Adolescent↗

Survey of Australian isotretinoin prescribing.

In Australia, dermatologists have been designated as the sole prescribers of isotretinoin and thus we are in a unique position to audit national usage of the drug. Questionnaires were sent by the Australasian College of Dermatologists to all 204 practising Fellows in Australia. The aim was to study the number and type of patients treated with isotretinoin, the manner in which the drug is prescribed, adverse reactions and the number of pregnancies occurring during and after treatment. Judging from the 85% of questionnaires which were returned, isotretinoin is an effective and well-tolerated drug for the treatment of severe nodulocystic acne. In the five years that isotretinoin has been used in Australia, 11 pregnancies while taking the drug were reported. These pregnancies occurred despite exhaustive counselling by dermatologists and the patients being fully aware of the risks to the fetus and the need for adequate contraceptive measures. With one exception, all agreed to have a therapeutic abortion. There were two reports of congenital abnormalities after cessation of treatment, neither of which were thought to be related to isotretinoin. In several regions where a dermatologist is not available, a specialist physician may prescribe isotretinoin according to State Health regulations.

Acne Vulgaris↗

Isotretinoin: cost-benefit study.

Isotretinoin is a well-established, effective treatment for severe nodulocystic acne. An important consideration which may limit the prescription of isotretinoin is its cost. Based on a literature review, we have compared isotretinoin with the conventional combination of antibiotics and topical therapies for the treatment of severe nodulocystic acne in terms of cost and benefit. Our results show that when duration of treatment is considered, isotretinoin is cheaper and significantly more effective.

Acne Vulgaris↗

Dilemmas facing surgical research in the '90s.

Surgical research in the '90s will need to address several general problems. This paper discusses the role of informed consent in clinical trials, animal experimentation in surgical research, and the importance of research in both undergraduate and postgraduate education.

Animal Testing Alternatives↗

Yeast KEX1 protease cleaves a prohormone processing intermediate in mammalian cells.

A vaccinia virus vector was used to express the yeast KEX1 gene, which encodes a prohormone carboxypeptidase specific for the removal of basic amino acids from prohormone processing intermediates, in mammalian cells. When produced in BSC-40 cells, Kex1p was localized to the perinuclear region and conferred a large increase in enzymatic activity characteristic of this carboxypeptidase. Expression of the KEX1 gene together with the yeast KEX2 gene, which encodes a prohormone endopeptidase specific for cleavage at pairs of basic amino acids, and the mouse proopiomelanocortin (mPOMC) cDNA in BSC-40 cells resulted in the full conversion of mPOMC to mature peptides including gamma-lipotropin. This in vivo processing of mPOMC to mature peptides by the KEX2/KEX1 gene products demonstrates a significant functional homology of the basic prohormone processing machinery in yeast and neuroendocrine cells.

Animals↗

Alpha- and beta-mannosidoses.

Clinical, pathological and biochemical findings in the mannosidoses are described. Family studies showed granulocyte-rich white cell fractions to be the tissue of choice for carrier detection in beta-mannosidosis. Metabolic labelling studies using [3H] mannose demonstrated accumulation of Man beta 1-4GlcNAc in cultured skin fibroblasts from a patient with this condition. Alternative methods of egress from lysosomes were suggested for this compound by its secretion into culture medium and apparent reduction of storage with time in cultures. beta-mannosidase deficient goats are not thought to be a true animal model of the human condition, as although they showed a similar enzyme deficiency, the clinical presentation is much more severe and the major storage material (Man beta 1-4GlcNAc beta 1-4GlcNAc) is different.

Animals↗

Recurrence of colorectal cancer and perioperative blood transfusion. Is blood storage time important?

In a prospective study of 35 patients undergoing surgery for colorectal cancer, the mitogenic activity of plasma was measured using 3T3 Swiss fibroblasts as target cells. Transfused patients exhibited a 100 percent increase in mitogenic activity over preoperative values compared with no significant change in nontransfused patients. Samples were taken from blood during 28 days of storage following donation, and mitogenic activity measured. The mitogenic activity increased with storage time, the principal changes occurring from the end of the second week. The increased mitogenic activity in patients following transfusion and in stored blood may be a factor in the mediation of the deleterious effect of transfusion on recurrence in colorectal cancer and perhaps "fresh" blood, if required, should be used.

Blood Cells↗

Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis.

Primary biliary cirrhosis is characterized by the presence of autoantibodies to mitochondria with specific reactivity to proteins of 74 and 52 kilodaltons (kd). The 74-kd mitochondrial protein is the E2 component--dihydrolipoamide acetyltransferase--of the pyruvate dehydrogenase complex, and the 52-kd protein is the equivalent E2 component--dihydrolipoamide acyltransferase--of the branched-chain alpha-keto acid dehydrogenase complex. Current methods for the detection of antibodies to these proteins lack specificity or sensitivity, or they are time-consuming and not readily available. We therefore developed an enzyme-linked immunoassay to quantify specific antimitochondrial antibodies in patients with primary biliary cirrhosis. Recombinant polypeptides coding for both the 74-kd and the 52-kd mitochondrial autoantigens were used to analyze 217 coded serum samples, including samples from 93 patients with primary biliary cirrhosis and 124 controls, for reactivity by our immunoassay, immunoblotting, and immunofluorescence testing. Serum samples from 89 of the 93 patients with primary biliary cirrhosis reacted with either the pyruvate dehydrogenase-E2 or the branched-chain alpha-keto acid dehydrogenase protein. None of the 124 control samples from healthy volunteers (n = 86) or patients with primary sclerosing cholangitis (n = 38) had significant reactivity. Our results indicate that the use of recombinant, cloned autoantigens provides a simple, accurate, and rapid method of quantifying and monitoring the levels of specific mitochondrial autoantibodies in the serum of patients with primary biliary cirrhosis.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Chorionic villus sampling: diagnostic uses and limitations of enzyme assays.

Control ranges for enzymes in uncultured chorionic villi were established, based on: (1) 21 of 22 enzymes (mainly lysosomal) in villi had similar properties to the enzyme in cultured fibroblasts; (2) isoenzyme patterns in villi were similar to those in fibroblasts for five lysosomal enzymes but different for aryl sulphatases; (3) control ranges were determined for 12 enzymes in abortion villi and for 21 enzymes in biopsy villi, values tending to be higher in the latter for those enzymes studied in both types of sample; (4) storage of samples under various conditions revealed no major changes in activity of seven lysosomal enzymes. A number of potential pitfalls in the use of chorionic villus samples for diagnosis of metabolic disorders by enzyme assay are described: (1) the presence of aryl sulphatase C in chorionic villi, an isoenzyme which may interfere in assays of aryl sulphatase A; (2) the presence of maternal enzyme in chorionic villus material illustrated by the detection of the A isoenzyme of B-hexosaminidase in chorionic villus from a pregnancy affected with Sandhoff's disease; (3) the finding of falsely normal levels of alpha-iduronidase in chorionic villus samples from a pregnancy affected with Hurler's disease, probably due to contamination with maternal tissue which has relatively high levels of this enzyme compared with fetal chorionic material: (4) the inadequacy of indirect assays of incorporation of radiolabel into macromolecules using chorionic villi, for example [14C]propionate incorporation for prenatal diagnosis of methylmalonic aciduria. Provided that such pitfalls are recognized and great care is taken in selection of villus samples and interpretation of results, chorionic villus sampling allows reliable prenatal diagnosis of a large number of disorders using enzyme assays.

Chorionic Villi Sampling↗

Successful management of esophageal strictures without resection or replacement.

Esophageal resection or replacement has become the standard therapy for severe esophageal strictures chiefly because less aggressive methods generally have failed. We hereby report our experience with 12 consecutive infants and children who have been managed successfully by means of Stamm gastrostomy and string-guided esophageal dilatation, coupled with endoscopically guided four-quadrant intralesional steroid injection, protected by Nissen fundoplication when gastroesophageal reflux has been demonstrated. In six patients, the stricture(s) were caused by ingestion of lye. In five, they were associated with repair of esophageal atresia. In one, the etiology was never determined. The strictures averaged 3.5 cm in length (range, 1 to 10 cm); the severity of the lesions was indicated by the fact that, in all instances, patients were completely intolerant of solids, and was confirmed fluoroscopically by demonstration of significant luminal narrowing. A mean of 4.3 steroid injections (range, 1 to 8) was required to obtain complete remission of symptoms; there have been no complications except in one lye ingestion patient who developed a tiny perforation following the initial dilatation, which responded to antibiotics alone. All patients remain symptom-free; the mean length of follow-up is 6.2 years (range, 1 to 11 years). We conclude that string-guided esophageal dilatation, when coupled with endoscopically guided steroid injection, is a safe and reliable method for treatment of severe esophageal strictures, which should obviate the need for esophageal resection or replacement in most patients. Moreover, even if treatment should ultimately fail, a procedure of lesser magnitude than esophageal replacement will likely be possible.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗