PubMed HealthSearch

Biomedical subjects

R E Miller

Publications and source records attributed to R E Miller.

At least 19 recordsLinked to original sources

Pharmacokinetic parameters of recombinant mast cell growth factor (rMGF).

The gene product of the murine Steel (Sl) locus encodes an early-acting hematopoietic growth factor that is a ligand for the c-kit protooncogene. Several cDNAs for the Sl gene product, known as mast cell growth factor (MGF), stem cell factor (SCF), or kit ligand (KL), have recently been isolated, and both soluble and membrane-associated versions have been shown to be biologically active. The potential for therapeutic usage of recombinant MGF (rMGF) indicated a need for determining the biodistribution and elimination parameters of this cytokine. Pharmacokinetic studies demonstrated that radiolabeled rMGF had a distribution half-life of 2 min and an elimination half-life of 2.1 h in wild-type mice following iv injection, during which a striking localization of labeled rMGF in the lungs was noted. When administered by subcutaneous injection the elimination half-life was prolonged to 8.4 h. The primary sites of rMGF elimination appeared to be the kidneys and the liver. Pharmacokinetic analysis of labeled rMGF in mutant Sl/Sld mice, which are mast cell deficient, demonstrated similar distribution and elimination half-lives compared to wild-type mice (1.4 min and 1.8 h, respectively). In addition, the biodistribution pattern of the labeled rMGF in Sl/Sld mice was similar to that observed in wild-type mice, including the striking localization to the lungs. Binding of radiolabeled rMGF to lungs in vivo subsequent to iv injection was completely inhibited by excess unlabeled rMGF. Interestingly, mice that received an iv injection of the higher doses of rMGF (15 micrograms) demonstrated profound respiratory distress and hypotension within minutes of administration. Histologic analysis of lungs from such mice revealed extensive mast cell degranulation, which was associated with vasodilatation and pronounced hyperemia of virtually all pulmonary vessels. The respiratory distress in normal mice was probably a consequence of mast cell degranulation induced by rMGF since similar findings were not observed in Sl/Sld mice injected with identical concentrations of rMGF.

Animals

Enterocylsis: the small bowel enema. How to succeed and how to fail.

Enteroclysis, the infusion of contrast medium directly into the small bowel, is a precise, rapid method for thorough small bowel examination. This technique demonstrates far more pathology than any other method when it is properly executed. However, the examination is sure to fail with poor techniques, thereby discrediting a superb method. Experience has shown that failures are usually due to inadequate technique or poor judgment or both during the examination. This article covers the proper and improper techniques of the examination and gives examples of each. The most common problems that arise during the examination are discussed in the order in which they usually develop.

Adult

Gastrointestinal radiography with glucagon.

This report summarizes the results of nine diagnostic radiographic studies done double blind crossover comparing glucagon to placebo and to anticholinergic drugs in volunteers. In seven studies the subjects were administered drug intramuscularly and in two studies intravenously. There were five diagnostic studies of the upper gastrointestinal tract, one for esophageal varices and three of the colon. The results indicate that glucagon can be given intramuscularly and intravenously. When given intravenously it has a rapid onset and predictable length of action depending on the dose given. Reports of side effects were few consisting primarily of nausea and or vomiting. These results indicate that glucagon is the drug of choice for hypotonic diagnostic examinations.

Atropine

Automated cervical cytology screening: performance requirements and instrument evaluation.

Continuing progress towards automation of cervical cancer screening requires that criteria for clinical acceptability of automated systems be defined, and that methods be devised for effectively evaluating new technology. The potential roles of automation in cervical cancer detection, performance requirements, instrument evaluation and useful contributions from tuberculosis screening, automated white blood cell differential counting, signal detection theory and decision theory are discussed.

Automation

Neural release of glucagon is inhibited by hyperglycemia and enhanced by phentolamine.

Using an innervated, cross-perfused, canine pancreas-stomach-duodenum preparation, direct neural effects on the immunoreactive glucagon secretion rate (GSR) were separated from blood-borne influences. Both splanchnic nerves were cut above the diaphragm and stimulated simultaneously for three separate 10-min-long periods, twice before and once during a pancreatic arterial phentolamine infusion. The extent of the decreases in GSR that occurred after nerve section was inversely correlated with the arterial plasma glucose concentration at the time of section. Splanchnic nerve stimulation caused a significant increase in GSR. Similar stimulation during a pancreatic arterial phentolamine infusion caused a significantly greater increase. Rapid infusion of glucose near the end of the experiment caused a significant decrease in GSR, demonstrating the responsiveness of the preparation. These data were collected in conjunction with a study of neural influences on insulin secretion rates. It can be concluded that the central nervous system can alter the secretion rate of glucagon by direct neural means. Alpha-adrenergic blockade, in the presence of splanchnic nerve stimulation, enhances GSR.

Animals

Colonoscopy for rectal bleeding in childhood.

Undiagnosed rectal bleeding can pose a significant problem in the pediatric patient. A systematic and logical approach to the work-up of the child with rectal bleeding is necessary for prompt and accurate diagnosis. It is our impression that the addition of colonscopy in carefully selected patients will decrease the number of children with undiagnosed significant rectal bleeding.

Adolescent

Regulation of glutamine synthetase in cultured 3T3-L1 cells by insulin, hydrocortisone, and dibutyryl cyclic AMP.

The 3T3-L1 mouse fibroblast cell line develops morphological and biochemical characteristics of adipocytes when maintained at confluence. This conversion to adipocytes is accelerated by addition of insulin to the culture medium [Green, H. & Kehinde, O. (1975) Cell 5, 19-27]. During the course of the insulin-mediated adipocyte conversion, the specific activity (units/mg of protein) of glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] increases more than 100-fold. The specific activities of hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) and glucose-6-P dehydrogenase (D-glucose-6-phosphate:NADP(+) 1-oxidoreductase, EC 1.1.1.49) also increase but less dramatically (1.5- to 3-fold). In contrast, confluent cells maintained in the absence of insulin for the same time (12-20 days after confluence) display only minimal increases in the activity of these enzymes. Maintenance of confluent cells in culture medium lacking added L-glutamine has little, if any, effect on glutamine synthetase activity in either control or insulin-treated cultures. Treatment of confluent 3T3-L1 cultures with hydrocortisone (1 mug/ml) for 3 days prior to harvesting results in an increase in glutamine synthetase specific activity of 12-fold for control cultures maintained for 13 days in the absence of insulin and 1.4-fold for adipocyte cultures maintained for 13 days in the presence of insulin (10 mug/ml). Treatment of 3T3-L1 control cells and adipocytes with dibutyryl cyclic AMP (1 mM) plus theophylline (1 mM) decreases the glutamine synthetase specific activity and almost completely reverses the insulin- and hydrocortisone-mediated increases in enzyme activity. In contrast, treatment with dibutyryl cyclic AMP plus theophylline has relatively little effect on the specific activities of hexokinase or glucose-6-P dehydrogenase or on the protein content of the cultures. These data indicate that glutamine synthetase activity is hormonally regulated in 3T3-L1 cells.

Adipose Tissue

Dose response to intramuscular glucagon during hypotonic radiography.

In a study to determine a dose response to glucagon during hypotonic duodenography, 15 male and female volunteers received placebo and 0.25 mg 1 mg and 2 mg glucagon intramuscularly, double-blind and cross-over. When 0.25 mg glucagon was given, the onset of drug effect was approximately 13--18 min: the mean duration of moderate hypotonicity was approximately 4--7 min. The larger the dose, the greater the duration of drug action. When 2 mg glucagon was given, the onset of drug effect occurred in approximately 4--7 min; the mean duration of moderate hypotonicity was 22--32 min. There were no changes in pulse or blood pressure attributable to the drug with these doses, and reports of nausea and diarrhea did not increase significantly until a dose above 1 mg was given. One mg glucagon given IM is useful in hypotonic upper Gl radiographic examinations. The onset of hypotonicity was 8--10 min with a duration of 12--27 min when this dose was given. Few reports of side effects were attributable to this dose.

Adult

Double-blind radiographic study of dose response to intravenous glucagon for hypotonic duodenography.

This study was undertaken to determine a dose response to glucagon during hypotonic duodenography. Fifteen male and female volunteers received placebo and 0.25 mg, 0.5 mg, 1 mg, and 2 mg of glucagon intravenously, double-blind, and crossover. Onset of drug effect occurred in approximately 45 seconds, regardless of the dose of glucagon given. There was a significant (p less than 0.01) decrease in gastrointestinal tonicity with all doses. The larger the dose, the greater the duration of drug action. Satisfactory stomach, duodenal, and small bowel hypotonicity for radiography were obtained with 0.25 to 0.5 mg of glucagon given intravenously with few side effects.

Adult

The barium enema: a reassessment looking toward perfection.

In a crossover study of more than 300 double contrast colon examinations, including 2,200 radiographs, many common and some uncommon views were taken and compared. An optimal series of "routine" films and the order in which they should be taken are presented. This will produce a complete colon examination in the most efficient way. Some technical considerations are presented which proved necessary to produce a superb examination. This new routine represents a reduction in the number of films advocated by Welin and Miller in earlier publications. The findings are compatible with both air contrast and full column techniques.

Barium Sulfate

Polypoid colonic lesions undetected by endoscopy.

Fifty-four endoscopically missed colonic polypoid lesions reveal the limitations of colonic endoscopy. Colonoscopy failed to identify 31 of the lesions, whereas 24 lesions were initially missed by proctosigmoidoscopy. One polypoid tumor of the rectosigmoid junction was missed by both. Most undetected lesions ranged from 0.5 to 1.5 cm. Endoscopic and radiologic diagnostic techniques are clearly complementary. Their combined diagnostic accuracy exceeds that of either technique alone. If results of the two methods conflict, one or both should be repeated. With a combined approach, completely missed lesions can be kept at a minimum.

Adenocarcinoma