Search PubMed⌕ Search

Biomedical subjects

L D Hall

Publications and source records attributed to L D Hall.

At least 127 records · Page 7Linked to original sources

True water and fat MR imaging with use of multiple-echo acquisition.

The original Dixon method for chemical shift imaging of a two-component system is extended to a multiple-echo technique. Four echoes are used to gain all the information required to remove non-chemical shift-dependent phase changes and produce true fat and water images. Applications of the method both to a phantom and to human tissue are shown. This technique results in information comparable to that obtained from the Dixon method in half the imaging time and also gives an equivalent, if not slightly improved, signal-to-noise ratio.

Arm↗

Effect of pH on the nuclear magnetic resonance relaxivity of encapsulated solid paramagnetic substances.

Encapsulation, by acid-stable materials, of solid paramagnetic metal complexes based on sulphonated polystyrene ion-exchange resin, prevents the significant demetallation which otherwise occurs when the complexes are subjected to an acidic environment equivalent to that of the human stomach (pH 1-2). In turn, this protects the ability of those complexes to enhance the nuclear magnetic resonance (NMR) spin-lattice relaxation rate of water. Application of the results in the development of contrast agents for MR imaging of the gastrointestinal (GI) tract, in the evaluation of coatings used in drug formulations, and in the measurement of GI transit times of drugs is suggested.

Capsules↗

NMR measurement of the degree of oil/water partition of paramagnetic contrast media.

Magnetic resonance imaging techniques have been used to evaluate the oil/water partition of a series of stable nitroxide free radicals. The degree of partition, K, closely parallels the order of chemical polarity and lipophilicity of these compounds. This method also provides insight into both their nuclear magnetic resonance relaxation characteristics and pharmacokinetics.

Chemical Phenomena↗

Magnetic resonance imaging approaching microscopic scale: maturation stages of Acetabularia mediterranea reproductive caps.

The reproductive cap of the giant single-celled alga Acetabularia mediterranea (or A. acetabulum) has rays tapering from a width of about 400 microns at the circumference of the cap to about 30 microns at their junction with the stalk of the cell. This is ideal geometry for testing the current limits of spatial resolution of proton magnetic resonance imaging. In this work, resolution of features down to 40 microns is achieved. Maturation of the cap rays involves a major cytoplasmic reorganization, from continuous cytoplasm and a central vacuole in each ray to bundles of cysts surrounded by aqueous solution. This work shows that an intermediate stage in the change can be highlighted in images by relaxation time (T1) contrasting.

Acetabularia↗

Magnetic resonance imaging of the delivery of a paramagnetic contrast agent by an osmotic pump.

The successful application of Magnetic Resonance Imaging (MRI) in verifying the in vitro delivery action of an osmotically-driven pump (Alzet 2ML1) is described. MRI detection of drugs commonly used with such pumps is not yet possible because of the low signal intensity of present MR techniques. So we employed a paramagnetic contrast agent (gadolinium diethylene triamine penta acetic acid) of molecular weight comparable to commonly used drugs, and solutions of comparable concentration and viscosity. The study highlights the potential of this approach in the evaluation of in vivo drug delivery systems.

Contrast Media↗

Gastric inhibitory polypeptide in obesity and diabetes mellitus.

Gastric inhibitory polypeptide (GIP) concentrations may be influenced by obesity, diabetes, and glucagon deficiency and be under feedback inhibition by insulin. To assess these factors, insulin-dependent diabetic, totally pancreatectomized diabetic, and lean and obese noninsulin-dependent diabetic patients were studied twice, once during partial insulin withdrawal and again when euglycemia was achieved before and after mixed meal ingestion, using an artificial endocrine pancreas. The results were compared to those from weight-matched lean and obese nondiabetic subjects. No significant differences in postprandial GIP responses were found between lean and obese nondiabetic subjects. Despite basal and postprandial hyperglycemia, the GIP responses to the mixed meal were not significantly different between insulin-deficient (insulin-dependent and totally pancreatectomized) patients and lean nondiabetic subjects. In addition, there were no significant differences in postprandial GIP responses between insulin-dependent and totally pancreatectomized patients. In contrast, lean and obese noninsulin-dependent diabetic patients had reduced GIP responses compared to weight-matched nondiabetic subjects (mean +/- SE, 37.9 +/- 5.4 vs. 67.1 +/- 10.8 ng ml-1 240 min-1, respectively; P less than 0.05). This difference was entirely due to the reduced GIP responses in obese noninsulin-dependent diabetic patients compared to those in obese nondiabetic subjects (32.1 +/- 7.9 vs. 76.9 +/- 18.2 ng ml-1 240 min-1, respectively; P less than 0.05); the postprandial GIP responses were not significantly different between lean noninsulin-dependent diabetic patients and lean nondiabetic subjects. Insulin infusion by an artificial endocrine pancreas resulted in postprandial insulin and glucose profiles that approximated those of nondiabetics, but did not significantly alter GIP responses to the mixed meal (48.2 +/- 5.5 ng ml-1 240 min-1) in the 18 diabetic patients compared to results obtained with sc insulin treatment (42.2 +/- 5.2 ng ml-1 240 min-1). In conclusion, postprandial GIP responses are normal in obese nondiabetic subjects and insulin-deficient diabetic patients and are blunted in obese, but not in lean, noninsulin-dependent diabetic patients. In addition, GIP does not appear to be under feedback inhibition by insulin or influenced by glucagon deficiency in diabetes.

Adult↗

Effects of size, time of day and sequence of meal ingestion on carbohydrate tolerance in normal subjects.

The effects of size, time of day and sequence of meal ingestion were determined in healthy subjects using a Latin square design. Plasma glucose, insulin and gastric inhibitory polypeptide, but not glucagon, were correlated with meal size. Plasma glucose, but not insulin, gastric inhibitory polypeptide or glucagon, were greater later in the day. The progressive decline in carbohydrate tolerance from 08.00 to 18.00 h was associated with impaired insulin secretion estimated by C-peptide, and with impaired insulin action.

Adult↗

Prandial insulin requirements in insulin-dependent diabetics: effects of size, time of day, and sequence of meals.

To assess the effects of size, time of day, and sequence of meals on insulin requirements determined by an artificial endocrine pancreas, eight insulin-dependent diabetics ate meals of 12.5%, 25%, and 50% of total calories (30 Kcal/kg) at 0800, 1300, and 1800 on each of 3 separate days in a randomized order in one of two sequences in a three by three Latin square design. Plasma glucose and free insulin concentrations and amounts of insulin infused by the artificial endocrine pancreas were associated with meal size (P less than 0.001) but not with time of day of meal ingestion (analysis of variance). The sequence of meal ingestion did not alter integrated plasma glucose responses, but did influence the meal-related amounts of insulin infused. Thus, consideration should be given to meal size and sequence of meal ingestion but not time of day of meal ingestion when determining prandial iv insulin requirements.

Adult↗

Subcutaneous versus intraperitoneal administration of insulin on post-prandial hyperglycaemia and glucose turnover in alloxan diabetic dogs.

The effects of subcutaneous and intraperitoneal insulin delivery by a closed-loop insulin infusion device on post-prandial hyperglycaemia and rates of glucose appearance and disappearance were compared in alloxan diabetic dogs. No differences in basal or post-prandial values or patterns of response were observed between the two routes of insulin delivery. In addition, the amounts of insulin infused and the plasma insulin concentrations achieved were not different for the two routes of insulin administration. These studies demonstrate that in the dog there appears to be no difference in the pattern of disposal of glucose from a mixed meal when insulin was administered intraperitoneally or subcutaneously at the rates of insulin infusion used in these experiments.

Alloxan↗

Comparison of peripheral and portal venous insulin administration on postprandial metabolic responses in alloxan-diabetic dogs. Effects of identical preprogrammed complex insulin infusion waveforms.

The optimal route for insulin administration by insulin infusion devices has not been established. To assess the differences between the peripheral venous and portal venous routes of insulin administration on postprandial metabolic responses, six alloxan-diabetic dogs were studied on four occasions. On the first, the insulin infusion rates given by the Biostator for disposal of a mixed meal were recorded electronically. On two subsequent occasions, these insulin infusion profiles were administered by a peripheral vein. On an additional occasion, the identical insulin infusion profile was given via the portal vein. No differences were observed in basal or peak plasma glucose, insulin, glucagon, branched chain amino acids, and lactate concentrations between portal and peripheral venous insulin administration. Furthermore, no differences in isotopically ( [2-3H]glucose) determined rates of systemic glucose appearance and disappearance were observed between the two routes. Although preprandial plasma alanine concentrations were greater when insulin was infused via the portal vein, the postprandial increments did not differ from those observed during infusion of insulin by a peripheral vein. These studies suggest that under the current experimental conditions, there appears to be no difference in the disposition of a mixed meal, measured as net whole body glucose appearance and disappearance rates, when insulin is administered in an open-loop fashion via either a peripheral or the portal vein.

Alanine↗

Acetaldehyde--enkephalins: structure proof and some conformational deductions from one- and two-dimensional proton nuclear magnetic resonance spectra.

The structure of the adduct formed by reaction of acetaldehyde and Met5-enkephalin has been determined by analysis of 400-MHz proton spectra: two-dimensional J spectroscopy was used to resolve and measure virtually all the overlapping resonances, and decoupling difference spectroscopy was used to assign the resonances. Suitable manipulation of the two-dimensional data allowed analysis of alpha-CH resonances which were completely buried under a water signal and of amide NH resonances which overlapped in both dimensions. The adduct was shown to be a mixture of two diastereoisomers, each containing a 2-methylimidazolidin-4-one ring formed by condensation of an acetaldehyde molecule with the N-terminal amino group and Gly2 amide nitrogen. Analysis of the NMR data suggests that the folded conformation characteristic of native enkephalins in dimethyl-d6 sulfoxide is not important in these derivatives.

Acetaldehyde↗

Effect of peripheral versus portal venous administration of insulin on postprandial hyperglycemia and glucose turnover in alloxan-diabetic dogs.

The effects of peripheral venous and portal venous delivery of insulin by a closed-loop insulin infusion device (Biostator GCIIS) on postprandial hyperglycemia and rates of glucose appearance, disappearance, and clearance were compared in alloxan-diabetic dogs. The amounts of insulin required and the peripheral venous plasma insulin concentrations achieved were not different for the two routes of insulin administration. No statistically significant differences in postprandial hyperglycemia or patterns of glucose disposal were observed between the two routes of insulin delivery. These studies indicate that in terms of hepatic versus extrahepatic disposal of glucose, there appears to be no practical advantage of portal venous over peripheral venous administration of insulin when a closed-loop insulin infusion device is used.

Alloxan↗

Control of blood sugar in insulin-dependent diabetes: comparison of an artificial endocrine pancreas, continuous subcutaneous insulin infusion, and intensified conventional insulin therapy.

We compared the ability of closed-loop intravenous insulin infusion (i.e., an artificial "pancreas"), open-loop continuous subcutaneous insulin infusion, and intensified conventional insulin therapy (preprandial injections of regular insulin, with injection of long-acting zinc-suspension insulin before breakfast) to bring the hyperglycemia of insulin-dependent diabetic subjects to a level comparable to that of normal, nondiabetic subjects. The mean circadian levels of plasma glucose, mean amplitude of glycemic excursions, and M values (defined in Methods) did not significantly differ among the three regimens. Although these levels in the diabetic subjects approximated those in the normal subjects, the levels of plasma insulin, mean amplitude of glycemic excursions, and M values were significantly higher than those in normal subjects (P < 0.01). Therefore, at least on a short-term basis, all three regimens can produce comparable, nearly normal levels of blood sugar in such patients; moreover, closed-loop devices can be used to determine insulin requirements for conventional therapy.

Adult↗

Sepharose 4B as a matrix for affinity chromatography. A spin-labelling investigation using nitroxides as model ligands.

Nitroxide spin labels were attached to CNBr-activated Sepharose 4B directly and through oligoglycines and oo-amino-carboxylic acids of varying length. The homogeneity of the carbohydrate environments of directly attached labels was investigated by measuring dipolar interactions between nitroxides as a function of solvation and of spin dilution with a diamagnetic analogue, as well as by electron exchange between the nitroxides and paramagnetic metal ions in solution. Only the exchange experiment revealed any inhomogeneity, suggesting that a small proportion of sites may be less accessible than the majority. The distances between sites were sufficiently small to allow, in principle, multiple-site interactions between quite small proteins in solution and immobilized ligands. Reorientation of the label at the matrix, characterized by the correlation time t, became more rapid with increasing spacer length n. For n > 12, the decrease in t was less pronounced. The two types of spacer behaved similarly. Thus an ideal spacer length for affinity separations is 12 atoms; this is in good agreement with data from a variety of affinity separations. The results of electron spin resonance studies of the effect of non-aqueous solvent on directly and indirectly labelled Sepharose 4B were used to suggest reasons why enzymes immobilized on Sepharose may be stabilized to denaturing solvents.

Chromatography, Affinity↗

Spin-labelling of sialic acid in soluble and cell-surface glycoproteins.

A new, mild method is described for spin-labelling sialic acid residues in situ. The procedure involves the formation of C-1 sialamides and has been applied to a serum glycoprotein, a mucin, tissue sections from human colon, and erythrocyte membrane components. The selectivity of the method and its possible applicability to other types of labelling are discussed.

Colon↗