Search PubMed⌕ Search

Biomedical subjects

R P Miller

Publications and source records attributed to R P Miller.

At least 19 recordsLinked to original sources
PubMed1992

Bilateral choanal atresia associated with malformation of the anterior skull base: embryogenesis and clinical implications.

A number of craniofacial and systemic malformations have been described in association with choanal atresia. We report a case of bilateral choanal atresia associated with congenital absence of the cribriform plate, crista galli, and perpendicular plate of the ethmoid bone. The anterior skull base defect was detected by using high-resolution computed tomography with three-dimensional reconstructions. The findings support the mesodermal flow theory of choanal atresia, in which there is excess migration of neural crest cells into the developing nasal septum and posterior choanae. This occurs at the expense of cells that would otherwise form the rest of the ethmoid complex. Clinical implications include the need for adequate preoperative imaging of the anterior skull base and consideration of potential intracranial complications during surgical repair.

Abnormalities, Multiple↗
PubMed1991

Incidence of perforation with Goode T-tube.

Two groups of patients from the same era were retrospectively studied in Cincinnati and Chicago. In Cincinnati two subgroups were studied. The first group received myringotomy with insertion of a 'T'-shaped ventilating tube (75 patients, 140 ears, 147 insertions). Fifty-eight ears still had the tube in place, 31 had healed after spontaneous extrusion, 17 had healed after removal of the tube, 20 had persistent perforation after the tube was gone, 2 had a cholesteatoma, and 4 patients (7 ears) were lost to follow-up. The second set received myringotomy and insertion of a small grommet (Donaldson tube, 71 patients, 140 ears, 164 insertions) tympanostomy tube. None could be documented to still have the tube in place, 156 ears healed after spontaneous extrusion, none required removal, 3 ears had a persistent perforation after the tube was gone, none had cholesteatoma, and 5 patients (5 ears) were lost to follow-up. The perforation rate for the T-tube is 13.6% and for the grommet is 1.8% (P = 0.0005). In Chicago, 93 patients who received the Goode T style tube (175 ears, 175 insertions) prior to March, 1986 were evaluated. The degree of retraction of the tympanic membrane preoperatively was recorded. No ears still had the tube in place, 145 had healed after spontaneous extrusion or removal of the tube, 30 had persistent perforation 12 months after the tube was gone, 4 had a cholesteatoma, and 8 patients (15 ears) were lost to follow-up. The rate of perforation is 18.8% which is not statistically different from the Cincinnati rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Chicago↗
PubMed1990

Beta subunit of (Na+ + K+)-ATPase contains three disulfide bonds.

Previous studies of titratable (Na+ + K+)-ATPase sulfhydryl groups have indicated the presence of one disulfide bond per mole of holoenzyme. This single disulfide cross-link was assigned to the beta subunit on the basis of the difference between the number of titrated "free" sulfhydryl groups and the total number of titrated sulfhydryl groups for each subunit [Esmann, M. (1982) Biochim. Biophys. Acta 688, 251; Kawamura, M., & Nagano, K. (1984) Biochim. Biophys. Acta 694, 27]. In the present study, beta-subunit tryptic peptides containing disulfide cross-links were identified and purified by HPLC. Two new peptides were generated from each disulfide-bonded peptide by reduction with dithiothreitol, and the amino acid compositions of these reduced peptides were determined. The data demonstrate that there are three disulfide bonds in the native beta subunit: 125Cys-148Cys, 158Cys-174Cys, and 212Cys-275Cys. The number of disulfide bonds in the beta subunit was also estimated by titration of sulfhydryl groups with [14C]iodoacetamide. Six sulfhydryl groups were identified: two sulfhydryl groups were titrated without prior reduction, and four were identified only after reduction of the protein with dithiothreitol. These data, suggesting that the beta subunit contains two disulfide bonds, are inconsistent with the peptide isolation experiments, which directly identified three disulfide bonds in the beta subunit. This inconsistency was resolved by demonstrating that approximately 20% of each disulfide bond in the beta subunit was reduced prior to the start of the experiment, resulting in an underestimation of the number of disulfide-bonded sulfhydryl groups in the beta subunit from the titration experiments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

Uptake and distribution of lidocaine in fetal lambs.

The fetal uptake of lidocaine was measured continually and quantitatively during and after a constant rate intravenous (iv) maternal infusion into five chronically prepared pregnant ewes. Lidocaine, 6 mg/kg (base), was infused at a constant rate for 1 h and measurements continued to 5 h. Rate of fetal uptake was determined from the product of the umbilical venous (UV) and fetal aortic (FA) concentration difference and umbilical blood flow (Qu). Total fetal uptake was determined by integrating fetal uptake rate with respect to time. Maternal and fetal protein binding was determined, and its effect on fetal blood concentrations was evaluated. Mean total fetal uptake as it related to time and infused dose increased linearly (r = 0.998, P less than 0.001) with a constant, weight-normalized fetal-maternal dose fraction of 0.45 during the infusion. Despite rapidly declining blood concentrations after the infusion, uptake increased an additional 17%. The sevenfold variation in uptake appeared to be inversely related to the biodegradation rate of lidocaine. Fetal-maternal concentration ratios (F/M) increased during declining blood concentrations. Protein binding determinations for maternal and fetal blood were 43.6 +/- 2.48% and 26.9 +/- 1.59%, respectively. These values were used to calculate the F/M in conjunction with the maternal and fetal pH. At maternal-fetal equilibrium the calculated F/M, 1.0 +/- 0.05, closely approximated the observed, 1.0 +/- 0.03. Variations in lidocaine concentrations among the vital organs 4 h after the infusion were small, but high concentrations of metabolites were found in the lungs and kidneys. The results challenge the validity of placental transfer estimates commonly based on the F/M and umbilical cord blood concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Renal secretion and hepatic clearance of human multiple renin forms.

Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity.

Adult↗
PubMed1990

Motivating adolescents to reduce their fines in a token economy.

Adolescents on a 16-bed token economy ward of a state hospital were subjected to four interventions in a seven-phase experiment to reduce the number of fines they received each day. Phase I was a four-week baseline period. Phases II and III were four- and five-week periods, respectively, in which residents were awarded tickets for a weekly $10 lottery each day they were at or below a changing criterion of daily fines. In Phase IV, residents received coupons, exchangeable for money, for days with zero fines. Phase V was a return to baseline. Phase VI was a one-week period in which daily lotteries for $1 were held, with the criterion for receiving a ticket being zero fines on the previous day. Phase VII was a one-week return to baseline. No significant differences in average fines per day, number of residents meeting criteria, or mean number of zero-fine days per week were found across phases. Results are discussed in terms of amount and immediacy of reinforcement, other opportunities to gain money, possible rebelliousness of the residents against the increased aversiveness of fines, and implications for further research.

Adolescent↗
PubMed1989

The influence of assay variability on pharmacokinetic parameter estimation.

The impact of assay variability on pharmacokinetic modeling was investigated. Simulated replications (150) of three "individuals" resulted in 450 data sets. A one-compartment model with first-order absorption was simulated. Random assay errors of 10, 20, or 30% were introduced and the ratio of absorption rate (Ka) to elimination rate (Ke) constants was 2, 10, or 20. The analyst was blinded as to the rate constants chosen for the simulations. Parameter estimates from the sequential method (Ke estimated with log-linear regression followed by estimation of Ka) and nonlinear regression with various weighting schemes were compared. NONMEM was run on the 9 data sets as well. Assay error caused a sizable number of curves to have apparent multicompartmental distribution or complex absorption kinetic characteristics. Routinely tabulated parameters (maximum concentration, area under the curve, and, to a lesser extent, mean residence time) were consistently overestimated as assay error increased. When Ka/Ke = 2, all methods except NONMEM underestimated Ke, overestimated Ka, and overestimated apparent volume of distribution. These significant biases increased with the magnitude of assay error. With improper weighting, nonlinear regression significantly overestimated Ke when Ka/Ke = 20. In general, however, the sequential approach was most biased and least precise. Although no interindividual variability was included in the simulations, estimation error caused large standard deviations to be associated with derived parameters, which would be interpreted as interindividual error in a nonsimulation environment. NONMEM, however, acceptably estimated all parameters and variabilities. Routinely applied pharmacokinetic estimation methods do not consistently provide unbiased answers. In the specific case of extended-release drug formulations, there is clearly a possibility that certain estimation methods yield Ka and relative bioavailability estimates that would be imprecise and biased.

Biometry↗
PubMed1989

AAQUANT: a computer program for quantitative amino acid analysis of proteins and peptides.

Quantitative amino acid analysis is an important tool used in the characterization and structural determination of peptides and proteins. A new computer program, AAQUANT, has been developed specifically to aid researchers in analyzing amino acid composition data. AAQUANT calculates amino acid recoveries, including 95% confidence intervals, following acid hydrolysis of peptides and proteins, and also includes useful routines to locate regions of a specified amino acid composition in known protein sequences, compute amino acid composition reports of known protein sequences, generate proteolytic digestion maps of proteins, and create and edit protein sequence data files. This report describes the AAQUANT routines, and demonstrates the use of the program.

Amino Acid Sequence↗
PubMed1989

Update of the Cincinnati experience in pediatric laryngotracheal reconstruction.

Surgical endeavors in the field of laryngotracheal reconstruction in children have received much interest in the past 15 years. A unique experience with laryngotracheal reconstruction in 203 children is reviewed. The majority (194) of the cases were classified as acquired; only nine were classified as congenital. Excluded from the study were those cases of stenoses managed endoscopically, all resections and end-to-end anastomoses, all anterior cricoid split procedures, and all cases of anterior glottic stenosis repaired by a laryngeal keel. The degree of stenosis was graded into four categories. Five different methods of laryngotracheal reconstruction were used depending on the pathologic lesion in the larynx and trachea. Of the 203 children, 186 (92%) were decannulated. The results support the use of laryngotracheal reconstruction in children with grades 2, 3, and 4 laryngeal stenosis.

Cartilage↗
PubMed1989

An appeals system for fines received by adolescents in a token economy.

A system is described wherein adolescents participating in a token economy at a state hospital were allowed to appeal fines received from staff. Appeals were heard by a board composed of three residents and a psychology intern. The board met weekly and had full power to rescind or uphold fines. Before initiation of the appeal system, residents complained vigorously about fines received and about the "unfairness" of the staff and the token system, frequently denying responsibility for the infractions involved. Although almost half the fines were upheld, there were practically no more complaints of unfairness, and denials of responsibility declined drastically. The number of residents appealing fines fell from an average of four per week to less than one per week after the system had been in effect for one and one-half months. When asked why the system was not being used more often, residents grudgingly volunteered that most of the fines received were fair. It was not possible to determine whether this was due to changes in residents' attitudes or to actual changes in fining behavior by staff. Results are discussed in terms of effects on residents, acceptance by staff, and implications for further research.

Adolescent↗
PubMed1988

All three potential N-glycosylation sites of the dog kidney (Na+ + K+)-ATPase beta-subunit contain oligosaccharide.

The beta-subunit of dog kidney (Na+ + K+)-ATPase is a sialoglycoprotein and contains three potential N-glycosylation sites. In this study, the oligosaccharide chains of purified dog kidney beta-subunit were labeled with tritium by oxidation with sodium periodate or galactose oxidase followed by NaB3H4 reduction. The beta-subunit was extensively digested by trypsin and the radioactive peptides were purified by HPLC. The enzyme, glycopeptidase A, which catalyzes the removal of N-linked oligosaccharide chains and the conversion of the glycosylated Asn residue to Asp, was used to demonstrate that a number of purified beta-subunit tryptic peptides were glycosylated. Amino-acid analysis of these beta-subunit peptides following glycopeptidase-A treatment revealed the expected Asn to Asp conversion for Asn-157, Asn-192 and Asn-264, demonstrating that all three potential N-glycosylation sites of the dog kidney beta-subunit are glycosylated. In addition, amino-acid sequence data suggest that a disulfide bond exists between Cys-158 and Cys-174.

Amidohydrolases↗
PubMed1979

Long acting cAMP analogues enhance sulfate incorporation into matrix proteoglycans and suppress cell division of fetal rat chondrocytes in monolayer culture.

The relationship between replication and the synthesis of matrix sulfated proteoglycans was investigated with fetal rat chondrocytes grown in monolayer culture. The effect of N6 O2' dibutyryl adenosine 3', 5' cyclic monophosphate (DBcAMP), adenosine 3', 5' cyclic monophosphate (cAMP), 8 Bromo adenosine 3', 5' cyclic monophosphate (8 Br-cAMP), sodium butyrate and hydroxyurea was examined. Between 0.05 and 0.5 mM DBcAMP, a dose related inhibition of cell division and stimulation of [35SO=/4] incorporation into matrix proteoglycans was demonstrated. At the higher concentrations of DBcAMP, cell division was completely inhibited and the enhancement of [35SO=/4] incorporation into matrix proteoglycans ranged between 40 and 120% (P less than 0.01). Utilizing 14C-glucosamine and photometric determination of proteoglycans with Alcian Blue, it was demonstrated that the increase in sulfate incorporation reflected enhanced accumulation of extracellular matrix. The effects of DBcAMP were mimicked by 8 Br-cAMP, suggesting they were mediated by the adenylyl cyclase system. cAMP (0.05-0.5 mM), sodium butyrate (0.1-0.5 mM) and hydroxyurea (0.5-5 mM) partially or fully inhibited cell division, but either failed or only slightly enhanced sulfate incorporation. The enhanced sulfated proteoglycan deposition promoted by DBcAMP began 8 to 12 hours after serum stimulation, its onset occurred prior to thymidine incorporation and the effect persisted for 28 hours. Determination of cell volume demonstrated an increase in size of DBcAMP treated chondrocytes between 8 to 12 hours, coincident with the onset of increased sulfate incorporation. These results are consistent with a model where matrix sulfated proteoglycan deposition by chondrocytes is mediated by intracellular cAMP levels and occurs in the G1 phase of the cell cycle.

Animals↗
PubMed1979

Insertion of Gibbons ureteral stents using endourologic techniques.

We describe our technique for the antegrade insertion of the redesigned Gibbons ureteral stent. We have used this technique for 19 kidneys without failures or complications. The advantages of internal drainage and of antegrade stent placement are discussed.

Catheters, Indwelling↗
PubMed1979

Percutaneous U-loop nephrostomy.

Single-tube nephrostomy drainage can be converted to U-loop drainage using percutaneous methods. Because only local anesthesia is required the technique can be used for patients who are poor operative risks.

Humans↗