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Biomedical subjects

A Muir

Publications and source records attributed to A Muir.

At least 73 records · Page 4Linked to original sources

Two regimens of lithium prophylaxis and renal function.

Two regimens of lithium prophylaxis with different pharmacokinetic characteristics were compared under double-blind conditions in 25 bipolar patients in remission already stabilized on lithium, to determine the relative effects of each regimen on renal function. Once-daily lithium carbonate (Priadal), which gives a peak lithium plasma level 2-3 h post-administration with a low level 24 h later, was compared with twice-daily lithium citrate (Litarex), which maintains a steadier 24 h plasma level. Patients were allocated randomly to one of the 2 regimens. They were seen monthly for clinical ratings over the course of 12 months. A comprehensive battery of renal function tests was undertaken at the start of the trial, between 6-9 months after the start and again after 1 year. No significant differences were observed in clinical outcome, side effects or renal function between the 2 regimens.

Acetylglucosaminidase↗

Thyroid scanning, ultrasound, and serum thyroglobulin in determining the origin of congenital hypothyroidism.

Congenital hypothyroidism (CH) can be due to an absent gland (athyrosis), an ectopic gland (usually lingual), or an inborn metabolic error (goiter). In this study, radionuclide scanning was compared with ultrasound (US) and serum thyroglobulin (Tg) concentration as a method of determining the cause of CH in 50 newborns. Mean serum Tg values were significantly lower in athyrotic children (7.9 pmol/L) than in either those with goitrous (149.1 pmol/L) or ectopic (60.5 pmol/L) glands, but there was marked overlap among all three groups. With the interpreter "blinded" to the radionuclide diagnosis, a cervical gland could be delineated reliably on US. All 12 goiters and five of five normal glands were identified. In contrast, the correlation between US and radionuclide scanning was poor in patients in whom there was no cervical thyroid tissue. Ultrasound failed to identify 13 lingual glands and was reported as normal in four of 12 children with no radionuclide uptake in the neck and biochemical hypothyroidism. Two children with absent thyroid glands on scanning were biochemically euthyroid. The serum of two others who had normal results of radionuclide studies showed persistent hypothyroidism. Thyroid scanning remains the most accurate diagnostic modality to determine the cause of CH. Serum Tg and cervical US have not been established as reliable alternatives.

Choristoma↗

Crystal structure of T4-lysozyme generated from synthetic coding DNA expressed in Escherichia coli.

The polypeptide produced by expressing a chemically synthesized gene coding for the amino-acid sequence of T4-lysozyme has been crystallized and subjected to X-ray diffraction. The crystal structure has been refined to a standard R-factor of 0.191 for data between 8 and 2 A resolution. The refined model is essentially the same as the well-known structure of wild-type T4-lysozyme determined previously by Matthews et al. (1987). Some small changes in the C-terminal region, which is important in maintaining the folded structure, have been noted. In addition to confirming that the synthetic gene product is very close to the wild type, this structure provides a benchmark for protein engineering experiments on the folding and the catalytic activity of this molecule by the method of gene synthesis.

Chromatography, High Pressure Liquid↗

Sex chromosome aneuploidy and Bardet-Biedl syndrome.

The inheritance of Bardet-Biedl syndrome is thought to be autosomal recessive. Of the approximately 500 case reports in the literature, three patients were found to have sex chromosome aneuploidy. The authors describe two siblings with Bardet-Biedl syndrome, one of whom has a unique sex chromosome aneuploidy with mosaicism, including deletion of the short arm of the X chromosome (45,X/46,X,del(X)(p21)). The possible significance of sex chromosome aneuploidy and the Bardet-Biedl syndrome is discussed.

Adult↗

Diagnostic value of cerebrospinal fluid myelin basic protein in patients with neurological illness.

The levels of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) have been evaluated as a method of detecting central nervous system (CNS) demyelination. MBP levels were measured in the CSF of 129 patients with neurological illnesses of whom 26 had a demyelinating illness. High levels of MBP were found in 81% of patients with recent episodes of demyelination but were not seen in patients with multiple sclerosis that was clinically stable or in remission. Patients with CNS trauma also had high levels of MBP in their CSF. The detection of a high level of MBP in CSF may be useful in the diagnosis of acute CNS demyelination but the finding is not specific for multiple sclerosis.

Demyelinating Diseases↗

The identification of a major product of the degradation of insulin by 'insulin proteinase' (EC 3.4.22.11).

We have studied a major product in the degradation of insulin by insulin proteinase (EC 3.4.22.11). Semisynthetic [[3H]PheB1]insulin and [[3H]GlyA1]insulin were used in the experiments. The structure of the fragment was deduced by observing the chromatographic and electrophoretic migration of the label both before and after further digestion of the fragment with proteinases of known specificity, with and without additional treatment by performic acid. Ambiguities were resolved by studying the behaviour of authentic fragments of known structure, isolated and characterized after digestion of intact insulin by proteinases of known specificity. We conclude that a major product in the degradation of insulin by insulin proteinase consists of a truncated section of the A chain, joined by the disulphide bridge B7-A7 to a truncated section of the B chain. The A-chain fragment consists most probably of residues A1-A13, and the B-chain fragment consists most probably of residues B1-B9. The similarity between this fragment and that found by other workers when insulin is degraded by intact hepatocytes is significant in the light of proposals that insulin proteinase is a possible participant in the physiological degradation of insulin by target cells.

Binding Sites↗

Acute and chronic haemodynamic and natriuretic effects of atriopeptin II in conscious rats.

The haemodynamic and natriuretic effects of an atrial natriuretic peptide were studied in conscious rats during acute and chronic administration of the peptide. Infusion of atriopeptin II (0.3 microgram/kg per min intravenously) for 60 min produced a fall in blood pressure and a rise in heart rate, accompanied by a significant decrease in renal and mesenteric blood flow. Despite the renal vasoconstriction, urinary sodium excretion increased markedly. These findings suggest that the hypotensive effect of atriopeptin II in conscious rats is not mediated by systemic vasodilatation, and that renal vasodilatation is not a prerequisite for the natriuretic action of this peptide. During infusion of atriopeptin II (24 micrograms/day) for 2 days, a small but persistent hypotensive effect was observed, which was accompanied by transient tachycardia. However, infusion of the same, or a higher (120 micrograms/day), dose of atriopeptin II for 4 days failed to produce any natriuretic effects. These results suggest that atrial natriuretic peptides are more important in acute than in chronic regulation of sodium excretion.

Animals↗

Regional specificity of iron uptake by small intestinal brush-border membranes from normal and iron-deficient mice.

Fe(II)-ascorbate uptake by purified small intestinal brush-border membrane vesicles prepared from proximal and distal segments was studied in normal and iron-deficient mice. Iron was maintained in a reduced, soluble form by a 20-fold excess of ascorbate at a physiological pH of 7.2-7.4. In normal mice, iron uptake by proximal membrane vesicles was three- to fourfold greater (approximately 1,700 pmol/mg prot) than from distal segments (approximately 500 pmol/mg prot). In iron-deficient mice, uptake of Fe(II) was also greater in proximal membranes (approximately 3,200 pmol/mg prot) than uptake from distal segments (approximately 350 pmol/mg prot), and the regional difference was almost 10-fold, without any change in distal segmental iron uptake. These results are consistent with the pattern of intestinal iron absorption in iron-replete and iron-deficient animals and indicate that regulatory changes in proximal intestinal brush-border membranes may account for the increased iron absorption known to occur in iron deficiency.

Animals↗

Iron absorption in normal and iron-deficient beagle dogs: mucosal iron kinetics.

Absorption of dietary iron requires uptake of iron by the brush border of the intestinal epithelial cells, intracellular transport, and transfer to the systemic circulation. In iron-deficiency anemia, iron absorption is greatly increased, but the individual steps responsible for this increase have not been identified. We have developed a method to evaluate the rate constants for each of these steps, and we report here our results in beagle dogs a) under normal conditions and b) after phlebotomy to produce iron-deficiency anemia. Simultaneous administration of oral 59Fe3+-citrate and intravenous 55Fe-transferrin was used to investigate the kinetics of mucosal iron transport. Plasma levels of both isotopes and the whole-body excretion pattern of 59Fe were monitored sequentially, and the fractional mucosal transport rates were estimated by nonlinear least-squares fit of a physiologically based mathematical model to these data. Under normal conditions the fractional rate of mucosal iron uptake from the intestinal lumen was rate limiting, being less than 1% of the fractional rate of either iron incorporation into the mucosal storage pool or transfer of iron from the mucosa to the plasma. After induction of iron-deficiency anemia, the fractional mucosal iron uptake rate increased sixfold (P less than 0.005), while the rate of incorporation into the mucosal storage pool decreased ninefold (P less than 0.02); in contrast, the fractional rate of iron transfer to the plasma did not change. These results indicate that the enhanced iron absorption in iron-deficiency anemia is attributable to an increase in mucosal iron available for transfer to the plasma, leading in turn to a net increase in iron absorption, despite a normal fractional transfer rate.

Anemia, Hypochromic↗

General practice care of non-insulin-dependent diabetes with fasting blood glucose measurements.

Non-insulin-dependent diabetes can be treated using two criteria, the fasting blood glucose concentration and body weight. The feasibility of this means of control, aiming for a fasting blood glucose concentration of less than 6 mmol/liter (108 mg/dl) has been investigated in 10 general practices. Eight practices now use the method routinely. A one-year follow-up in six practices is reported. The number of patients with a fasting blood glucose concentration of less than 108 mg/dl increased from 39 (26 percent) to 65 (59 percent). The mean fasting blood glucose concentration of all 112 patients was significantly (p less than 0.01) decreased from a mean of 148 to 113 mg/dl at three months, and subsequently increased to a still reduced (p less than 0.01) level of 126 mg/dl after one year. The mean hemoglobin A1c level was decreased (p less than 0.01). Six practices preferred to have special clinics at which fasting blood glucose meaurements were taken. Two practices achieved good results with the administration and tests being undertaken by a practical nurse, with supervision from the general practitioner. Assessment of control by four fasting blood glucose determinations a year is less expensive than regular urine tests, and may improve blood glucose control.

Adult↗

Arthropathy, hypouricemia and normal serum iron studies in hereditary hemochromatosis.

A patient manifesting the arthropathy of hemochromatosis without abnormal serum iron studies is described. Hemochromatosis was confirmed by liver biopsy. This case serves to emphasize the diagnostic value of the characteristic arthropathy of hemochromatosis. Our observations in this patient support the hypothesis that the pathogenesis of hereditary hemochromatosis differs from that of acquired iron overload states. The concurrent presence of hypouricemia is explored in this patient and in 18 other patients with hereditary hemochromatosis. Men with hereditary hemochromatosis were found to have lower serum uric acid levels than expected. In our patient, a renal defect in tubular reabsorption of uric acid appears responsible for hypouricemia. The apparent association of hemochromatosis and hypouricemia deserves further investigation.

Arthritis↗

Non-spherocytic haemolytic anaemia in mother and son associated with hexokinase deficiency.

The case history, laboratory findings and properties of the enzyme in a patient with hexokinase deficiency are reported. The mother had a haemolytic disorder of similar severity. In these cases the expression of the disease in both mother and son suggests a dominant mode of inheritance. This family further illustrates the necessity of taking the reticulocyte level into account when interpreting red cell enzyme levels.

Adult↗

Fetal tissue amino acid concentrations in argininosuccinic aciduria and in "maternal homocystinuria".

Free amino acid concentrations have been measured in the tissues of a fetus at risk for argininosuccinic aciduria and of an obligate heterozygous fetus in a mother homozygous for homocystinuria. Argininosuccinic acid was detected in all tissues studied of the homozygous affected fetus from the heterozygous mother. Abnormal concentrations of methionine and cystathionine were observed in the tissues of the fetus who was an obligate heterozygote for homocystinuria. These abnormal free amino acid concentrations occur early in fetal development and may be related to later brain dysfunction.

Amino Acid Metabolism, Inborn Errors↗