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Biomedical subjects

L Davidson

Publications and source records attributed to L Davidson.

At least 127 records · Page 7Linked to original sources
PubMed1991

Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin.

Nonobese diabetic (NOD) mice spontaneously develop an autoimmune form of diabetes associated with insulitis. A number of immunomodulatory therapies have been investigated as a treatment for the disease process. Oral administration of the autoantigens myelin basic protein and collagen type II suppresses experimental models of encephalomyelitis and arthritis. We have now found that oral administration of insulin delays the onset and reduces the incidence of diabetes in NOD mice over a 1-year period in animals administered 1 mg of porcine insulin orally twice a week for 5 weeks and then weekly until 1 year of age. As expected, orally administered insulin had no metabolic effect on blood glucose levels. The severity of lymphocytic infiltration of pancreatic islets was also reduced by oral administration of insulin. Furthermore, splenic T cells from animals orally treated with insulin adoptively transfer protection against diabetes, demonstrating that oral insulin administration generates active cellular mechanisms that suppress disease. These results show that oral insulin affects diabetes and the pancreatic cellular inflammatory process in the NOD mouse and raise the possibility that oral administration of insulin or other pancreatic autoantigens may provide a new approach for the treatment of autoimmune diabetes.

Administration, Oral↗
PubMed1991

Amino acid sequence of a globin from the sea cucumber Caudina (Molpadia) arenicola.

Coelomic cells from the sea cucumber Caudina (Molpadia) arenicola contain four major globins, A, B, C and D. The hemoglobins from this organism show unusual ligand-linked dissociation properties. The complete amino acid sequence of the D globin has been established. It is N-acetylated, consists of 158 residues and has a 10 amino acid N-terminal extension similar to that found in some other invertebrate globins. The C. arenicola D globin has an equal sequence identity (28%) with both alpha and beta human globins and as anticipated, is more closely related to these vertebrate proteins than are molluscan globins. The C. arenicola D globin shows a 59% identity with the globin I from the sea cucumber Paracaudina chilensis. The availability of the C. arenicola D globin sequence will aid the X-ray analysis of this protein and facilitate an understanding of the changes in subunit interactions that occur with cooperative ligand binding.

Amino Acid Sequence↗
PubMed1991

Effect of variation in infusion time and macrophage blockade on organ uptake of amphotericin B-deoxycholate.

Amphotericin B is administered as a colloidal suspension due to its insolubility in water. Macrophages, particularly those in the liver, have been implicated as the predominant cell type responsible for the uptake of colloidal amphotericin B. We examined the effect of infusion time and macrophage function to confirm the role of the macrophage in the uptake of amphotericin B. Prolonged infusion time (24 h compared to 6 h) resulted in significantly less hepatic and splenic accumulation of amphotericin B. Blockade of macrophage function with methylpalmitate also resulted in significantly decreased hepatic and splenic uptake of amphotericin B. Uptake of amphotericin B by lung macrophages was not significantly affected by methylpalmitate. The area under the serum concentration versus time curve was significantly higher in the group that received methylpalmitate compared to either the 6 or 24 h amphotericin B infusion groups. These results suggest that fixed macrophages play an important part in the pharmacokinetics of amphotericin B, and that increasing drug solubility may alter the pharmacokinetics of amphotericin B.

Amphotericin B↗
PubMed1991

Idiopathic gastroparesis is associated with a multiplicity of severe dietary deficiencies.

UNLABELLED: Idiopathic gastroparesis (IG), a disorder characterized by abnormally delayed emptying of food from the stomach, is associated with many symptoms that could have an impact on dietary intake. The intake of dietary protein, carbohydrate, fat, fiber, vitamins, and minerals was prospectively evaluated in patients with symptomatic IG and compared with asymptomatic controls. Twenty-four patients and 24 age- and sex-matched controls completed a detailed 7-day diet record while consuming a self-selected diet. Dietary information was entered into a computer and analyzed using the Nutranal program. Results were expressed as daily intake and percent recommended dietary allowance (%RDA) when applicable. Patients consumed a diet containing fewer calories than would have been predicted based on age, height, sex, frame, and weight (85% of calculated energy expenditure vs 100%) for controls. Although patients with IG consumed significantly fewer calories than controls (1112 kcal vs 1431 kcal), the proportion of fat (32% vs 34%), carbohydrate (49% vs 48%), and protein (17% vs 16%) was similar in the two groups. Intake of vitamins B6, vitamin C, folate, niacin, riboflavin, thiamine, calcium, copper, iron, magnesium, phosphorus, and zinc were below the %RDA. Intake of vitamin B12, vitamin C, folate, thiamine, niacin, magnesium, phosphorus, and zinc were significantly less than controls. Vitamin A intake was above the RDA and not different from that of controls. Prolonged t1/2 of solids correlated with diminished intake of protein, iron, niacin, and potassium. They correlated inversely with serum albumin in patients with idiopathic gastroparesis. CONCLUSION: Although eating less, patients with IG do not consistently alter the proportion of fat, carbohydrate, and protein in their diets. Because their diet is markedly deficient in a number of essential vitamins and minerals, dietary evaluation and counseling is suggested for all patients with idiopathic gastroparesis.

Adult↗
PubMed1989

Solubility and stability of amphotericin B in human serum.

The solubility and stability of amphotericin B in human serum in vitro was assessed using a sensitive high performance liquid chromatographic technique. The solubility of amphotericin B at concentrations ranging from 0.5 micrograms/ml to 10 micrograms/ml in human serum at pH 7.4, at 37 degrees C, and in 5% CO2 (simulated in vivo conditions) showed no significant difference compared with the solubility at 23 degrees C in room air after a 1 h incubation period. Dissolution of the colloidal suspension at a concentration of 2 micrograms/ml reached 81% in 3 min with a small increase in solubility by 60 min. Amphotericin B was very stable (less than 5% loss) in human serum at -20 degrees C for up to 14 days with only a 10% loss of drug at 6 months. In dimethylsulfoxide, however, losses at 6 months were greater than 60%. We conclude that amphotericin B solubilizes, but not completely, from a colloidal form in human serum under simulated in vivo conditions at 37 degrees C and at 23 degrees C in room air over 1 hour. Additionally, amphotericin B is stable in frozen serum for 6 months.

Amphotericin B↗
PubMed1987

Trabecular and cortical bone in the radii of women with parathyroid adenomata: a greater trabecular deficit, with a preliminary assessment of recovery after parathyroidectomy.

Radial bone mineral content (BMC) has been reported to be lower than normal in patients with hyperparathyroidism, but those measurements have been made with techniques which do not discriminate between trabecular and cortical bone. We have used a low radiation dose computed tomography technique to make differential measurements of trabecular and cortical bone in the radii of 18 out of 27 eligible female patients with surgically proven adenomata. Prior to parathyroidectomy there was a mean deficit of 40% (P less than 0.001) in trabecular bone density in the distal radius, and a deficit of 16% in cortical bone in the radius mid-shaft compared to normal values. Seventeen months after parathyroidectomy there was a small but significant increase in trabecular bone density in the distal radius in 13 of these patients, and no significant change in cortical bone. If these results represented the situation throughout the skeleton, it is possible that parathyroidectomy may provide some reduction in future risk of fracture in women with primary hyperparathyroidism.

Adult↗
PubMed1986

Clinical significance and etiology of infected catheters used for total parenteral nutrition.

Catheter related sepsis (CRS) is the most serious complication of total parenteral nutrition. Frequently, however, low rates of CRS are associated with a high incidence of infection of the catheter tip, the clinical significance of which is unclear. The relationships between CRS, infection of the catheter tip and infection at the site of catheter insertion have been investigated in 283 catheters of 257 patients receiving total parenteral nutrition. CRS occurred in only ten patients (3.5 per cent) whereas organisms were isolated from 108 catheter tips (38.2 per cent). The most common organism isolated was Staphylococcus epidermidis (66.7 per cent). Eight catheter tips were colonized from a distant septic focus. Organisms were isolated from 90 catheter tips which were removed electively from patients who displayed no clinical evidence of sepsis. There was a poor correlation between infected catheter tips and infected catheter insertion sites. Asymptomatic infection of the catheter tip appears to be of little clinical relevance, resulting in no patient morbidity. Contamination of the catheter tip during or after removal seems to account for a significant proportion of these infections.

Bacteria↗
PubMed1985

Comparative accuracy of computerized spatial vectorcardiography and standard electrocardiography for detection of myocardial infarction.

New computerized spatial vectorcardiographic variables were analyzed by discriminant analyses for group classification of 94 patients with acute myocardial infarction and 79 normal subjects. Using the integral of the sequential magnitudes of the spatial vectors during the period of initial abnormal depolarization (IAD) of the QRS at a discriminating value of 3 mv X msec., 87% of the subjects were correctly classified with a sensitivity of 85%; specificity of 88%; and an overall predictive accuracy of 87%, p less than .00001. The period of initial abnormal depolarization in which the vectors were integrated was determined by the first derivative of the sequential magnitudes of the spatial vectors of the QRS waveform (dm/dt). The mean value of dm/dt during the period of abnormal depolarization was a poor discriminating variable. The predictive accuracy of this new electrocardiographic criterion for diagnosis of myocardial infarction compared favorably with other computerized methods such as vectorcardiography, polarcardiography, Aitoff spatial trajectory, the 12-lead ECG derived by the Frank XYZ leads as well as the standard 12-lead ECG.

Computers↗
PubMed1985

Sulphate conjugation limits fluctuations in free catecholamines in phaeochromocytoma.

More than 80% of total noradrenaline (NA) and adrenaline (A) and nearly 100% of dopamine (DA) circulate in blood as sulphates, and it has been proposed that sulphate conjugation contributes to the inactivation of catecholamines (CA). Sulphate conjugation rapidly responds to changes in sympathetic activity and may buffer the haemodynamic and metabolic consequences of wide fluctuations in CA release in phaeochromocytoma. This hypothesis was tested in seven patients with phaeochromocytoma by consecutive measurements of plasma-free and conjugated NA, under resting conditions, before operation and at least 4 weeks after tumour removal. Free and total (free + sulphates) NA were markedly elevated before compared with 1-4 months after surgery. Similar elevations were seen in free and total A and free DA. Before surgery consecutive measurements of total NA, 5 min apart, were markedly different (17 +/- 4.1 and 13.7 +/- 4.4 ng/ml, respectively), whereas only small differences in free NA levels were present (4.1 +/- 1.5 and 4.3 +/- 1.8 ng/ml). These differences between total and free levels were also apparent for A and DA, but to a lesser degree. In three patients, fluctuations in total NA concentration greater than 12 ng/ml were associated with either no change (one patient) or changes of 0.6 and 2.8 ng/ml in free levels for the other two patients, respectively. Mean blood pressure (BP) varied less than 8 mmHg in these patients. These findings suggest that sulphate conjugation is a dynamic process which may limit wide fluctuations in free CA concentration during episodic secretory activity in phaeochromocytoma.

Adrenal Gland Neoplasms↗