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Biomedical subjects

J M Donovan

Publications and source records attributed to J M Donovan.

At least 37 records · Page 2Linked to original sources

Bladder stimulation therapy improves bladder compliance: results from a multi-institutional trial.

PURPOSE: We examined data from multiple institutions to determine whether intravesical bladder stimulation therapy is effective in improving bladder compliance by increasing bladder capacity and lowering bladder storage pressures. MATERIALS AND METHODS: The charts of 568 patients from 11 institutions were evaluated. Of the 568 patients 335 had adequate and accurate pretreatment and posttreatment urodynamic studies, and were included in this study. A total of 155 patients was from Children's Memorial Hospital, while the remaining 180 were from 10 other institutions. Bladder capacity and bladder capacity pressure were determined for each patient before and after therapy. RESULTS: Overall, 53% of patients had increased bladder capacity of 20% or greater after treatment (average increase 105 cc), which represents a 63% increase from pretreatment values. This increase occurred in an average of 1.9 years. Further analysis of this subset of patients revealed that in 90% intravesical storage pressures were decreased or maintained within a safe range (less than 40 cm. water). Evaluation of patients who did not respond to bladder stimulation with a 20% or greater increase in bladder capacity revealed that they had nearly normal bladder capacity before therapy. When the data on bladder capacity and bladder capacity pressure from Children's Memorial Hospital were compared to results from the 10 other institutions, there were no appreciable differences. CONCLUSIONS: Bladder stimulation is effective in increasing bladder capacity without significantly elevating storage pressure in a majority of patients. We conclude that this technique is safe and effective in improving bladder compliance, and that it is reproducible elsewhere.

Adolescent↗

Bile acid/phosphatidylcholine interactions in mixed monomolecular layers: differences in condensation effects but not interfacial orientation between hydrophobic and hydrophilic bile acid species.

Monomolecular layers of undissociated bile acids and membrane lipids at the air/water interface serve as useful models for the interactions between fully ionized bile salts and physiological membranes. Employing an automated Langmuir-Pockels surface balance, surface pressures and dipole moments were measured as functions of molecular area for six dihydroxy bile acids: ursodeoxycholic acid (UDCA), deoxycholic acid (DCA), chenodeoxycholic acid (CDCA), hyodeoxycholic acid (HDCA), allodeoxycholic acid (alloDCA), and 7 alpha,12 alpha-dihydroxycholanoic acid (7,12-OH-DCA), individually and in mixed mono-molecular layers with 1-palmitoyl-2-oleoyl-sn-3-glycerophosphatidylcholine (POPC) with and without cholesterol on a 5 M NaCl subphase at pH 2. In general, monolayers of hydrophilic bile acids (UDCA, HDCA) had lower collapse pressures and surface dipole moments than hydrophobic bile acids (CDCA approximately DCA approximately alloDCA < 7,12-OH-DCA). In binary mixtures with POPC, all bile acids including the synthetic 7,12-OH-DCA and the uncommon alloDCA condensed mixed monomolecular layers, with the degree of condensation correlating positively with bile acid hydrophobicity. In contrast, none of the bile acids caused further condensation of condensed POPC/cholesterol monomolecular layers. Surface dipole moments of binary bile acid/POPC +/- cholesterol mixtures demonstrated strict additivity, implying that no change in molecular orientation of the interface occurred over film compositions that varied from 0 to 100% bile acid. We conclude that the long axes of the steroid nuclei of dihydroxy bile acids remain parallel to the interface in mixed bile acid/POPC +/- cholesterol monomolecular layers under all conditions. We infer that fully dissociated hydrophobic and, to a lesser extent, hydrophilic bile salts condense phospholipid monomolecular layers and membranes in a similar fashion.

Bile Acids and Salts↗

The relationship between membrane fluidity and permeabilities to water, solutes, ammonia, and protons.

Several barrier epithelia such as renal collecting duct, urinary bladder, and gastric mucosa maintain high osmotic pH and solute gradients between body compartments and the blood by means of apical membranes of exceptionally low permeabilities. Although the mechanisms underlying these low permeabilities have been only poorly defined, low fluidity of the apical membrane has been postulated. The solubility diffusion model predicts that lower membrane fluidity will reduce permeability by reducing the ability of permeant molecules to diffuse through the lipid bilayer. However, little data compare membrane fluidity with permeability properties, and it is unclear whether fluidity determines permeability to all, or only some substances. We therefore studied the permeabilities of a series of artificial large unilamellar vesicles (LUV) of eight different compositions, exhibiting a range of fluidities encountered in biological membranes. Cholesterol and sphingomyelin content and acyl chain saturation were varied to create a range of fluidities. LUV anisotropy was measured as steady state fluorescence polarization of the lipophilic probe DPH. LUV permeabilities were determined by monitoring concentration-dependent or pH-sensitive quenching of entrapped carboxyfluorescein on a stopped-flow fluorimeter. The relation between DPH anisotropy and permeability to water, urea, acetamide, and NH3 was well fit in each instance by single exponential functions (r > 0.96), with lower fluidity corresponding to lower permeability. By contrast, proton permeability correlated only weakly with fluidity. We conclude that membrane fluidity determines permeability to most nonionic substances and that transmembrane proton flux occurs in a manner distinct from flux of other substances.

Acetamides↗

Cranial bone grafting in children.

Computed tomographic scans of 96 patients from newborn to 21 years of age were reviewed to assess the thickness of the skull and diploic space. Cranial thickness of the parietal bone used for calvarial bone harvest was assessed. Analysis of the data revealed that (1) cranial bone thickness may be predicted reliably as a function of age, (2) the growth velocity of increasing thickness of the parietal bone decreased with increasing age, and (3) presence of a diploic space may be predicted reliably as a function of age. On the basis of this analysis, we recommend performing split cranial bone grafting after the age of 3 years. In situ cranial bone grafting should not be planned prior to the age of 9 years.

Age Factors↗

Bone mineral disorders in children: evaluation with dual x-ray absorptiometry.

PURPOSE: To evaluate the utility of dual x-ray absorptiometry (DXA) in children with bone mineral disorders. MATERIALS AND METHODS: In phase 1, radial DXA was compared with single-energy photon absorptiometry (SPA) (n = 117). In phase 2, radial and lumbar bone mineral density (BMD) measured with DXA and second metacarpal cortical thickness were compared (254 examinations, 224 children). RESULTS: For radial BMD, DXA and SPA correlated well (r = .956) and SPA-equivalent values could be calculated from DXA measurements (mean residual error = 0.024 g/cm2). After controlling for age, sex, weight, and height, partial correlations were very small for lumbar BMD with radial BMD (r = .186) and lumbar BMD with cortical thickness (r = .158), and slightly better for radial BMD with cortical thickness (r = .544). Z scores also correlated poorly with no meaningful correlation for lumbar BMD with radial BMD (r = .07) CONCLUSION: In children with bone mineral disorders, radial DXA and SPA measurements correlate well. However, lumbar BMD, radial BMD, and cortical thickness correlate poorly and lumbar BMD frequently does not identify abnormality in patients with abnormal radial BMD. Lumbar BMD alone is not adequate for evaluation of bone mineral status in these patients.

Absorptiometry, Photon↗

Calcium affinity for biliary lipid aggregates in model biles: complementary importance of bile salts and lecithin.

BACKGROUND/AIMS: Despite putative roles of calcium in biliary physiology and gallstone formation, quantitative aspects of calcium binding to bile salt (BS) monomers, simple micelles, mixed micelles, and vesicles, which constitute the lipid aggregates in bile, remain unexplored. METHODS: Calcium activity was measured using the calcium electrode in pathophysiologically relevant model biles composed of either individual BS species or a physiological mixture of glycine and taurine conjugates, as functions of lecithin and cholesterol contents and total lipid concentration. RESULTS: Calcium binding increased with increasing BS concentrations and lecithin contents and varied with species (dihydroxy > trihydroxy BS) and with conjugation (unconjugated > glycine conjugates > taurine conjugates). Although lecithin/cholesterol vesicles did not bind detectable calcium, when taurocholate was incorporated into membrane bilayers, calcium binding was substantially greater than with equimolar BS alone. Added cholesterol did not alter calcium binding, despite cholesterol saturation of biliary lipid aggregates and induction of liquid crystalline and solid crystalline-phase transitions. CONCLUSIONS: In model biles, most calcium is bound to mixed micelles, with minor contributions by BS monomers, simple micelles, and vesicles. It is proposed that BS-induced binding of calcium to vesicles and mixed micelles may be important in nucleation of cholesterol and bilirubinates from native bile.

Bile↗

Elastic free energy of anisotropic helical ribbons as metastable intermediates in the crystallization of cholesterol.

We report measurements of the geometrical structure and temporal evolution of metastable helical intermediates in the pathway for cholesterol crystallization in native and model biles. We find that the lecithin component in the bile can dramatically affect the kinetics along this pathway. We also present a theoretical description of these helical intermediates using an elastic free energy appropriate for anisotropic bilayers of tilted chiral amphiphiles, which provides a quantitative description of the observed helical ribbon geometry and insight into the relative free energies of the observed metastable intermediates.

Bile↗

Pan-sulfation of bile salts markedly increases hydrophilicity and essentially abolishes self- and hetero-association with lecithin.

In chronic liver disease, partially and to a lesser extent completely (pan-)sulfated common bile salts are synthesized, yet little information is available concerning their physical-chemical characteristics. We studied solution properties of pan-sulfated common free, taurine and glycine-conjugated bile salts, and the interactions of taurodeoxycholate di-sulfate (TDC-S) with lecithin. By reverse-phase HPLC, pan-sulfated glycine and taurine-conjugated bile salts were very hydrophilic, with hydrophobic indices 1.7 to 2.5 units lower than their non-sulfated congeners. In contrast to non-sulfated species, pan-sulfated free and glycine-conjugated bile salts produced simple potentiometric titration curves without precipitation of bile salt below the pK'A of the carboxylic acids. By quasi-elastic light scattering, critical micellar concentrations of TDC-S fell from 28 mM in 0.15 M NaCl to 3 mM in 4.0 M NaCl, a value slightly higher than that of TDC. TDC-S formed very small micelles (hydrodynamic radii approx. 11A) that, in contrast to TDC, did not grow with increases in bile salt (7-66 mM) or NaCl (0.15-2.0 M) concentrations. TDC-S formed mixed micelles with lecithin in 0.15 M NaCl, but with a micellar zone drastically reduced compared with that of the non-sulfated congener. However, in 4 M NaCl, the micellar zone of TDC-S expanded and approached that of the non-sulfated parent compound. Therefore, under physiological conditions, pan-sulfation of common bile salts should largely eliminate their capacity to form mixed micelles with membrane lipids.

Bile Acids and Salts↗

Comparative evaluation of materials used for internal ureteral stents.

The materials used in the fabrication of self-retained internal ureteral stents should provide strength, flexibility, low surface friction, radiopacity, biodurability, biocompatibility, and reasonable unit cost. Polymeric biomaterials currently used for stent construction include polyurethane, silicone, Silitek, C-Flex, and Percuflex. Comparative evaluation of these materials in the context of the requirements for stent structure and function suggests advantages and disadvantages for all of them. We believe that the most important attributes for an internal ureteral stent are ease of insertion, effective restoration and maintenance of flow, resistance to migration, significant biodurability, and biocompatibility. Based on our physical testing of stents fabricated from these materials, as well as clinical and laboratory experience, we believe that C-Flex and Percuflex are the most suitable materials for stent construction.

Biocompatible Materials↗

Validation of a Portuguese form of Templer's Death Anxiety Scale.

To translate Templer's Death Anxiety Scale into the Brazilian Portuguese Escala de Ansiedade de Morte, linguistic validity was first established by back-translation and calculating bilingual split-half reliability coefficients. Even-numbered items achieved a minimally adequate .59, while the odd-numbered items attained a satisfactory .91. The internal consistency of the Escala (.77) matches that found for the original scale. The construct validity was tested by replicating the interactions of the English form with (1) the State-Trait Anxiety Inventory, (2) the Purpose-in-Life Test, and (3) Levenson's measure of locus of control. The Escala performed as expected, save for some difficulty with the locus of control measure.

Adult↗

Rapid determination by centrifugal ultrafiltration of inter-mixed micellar/vesicular (non-lecithin-associated) bile salt concentrations in model bile: influence of Donnan equilibrium effects.

We have developed the technique of rapid (< 2 h) centrifugal ultrafiltration to measure the inter-mixed micellar/vesicular (non-lecithin-associated) bile salt (BS) concentrations (IMC) of individual BS in model biles. This methodology uses a centrifugal concentrator with a reinforced membrane, through which a small fraction (< 15% total volume) of model biles was ultrafiltered by low centrifugal forces (1500 g 5-60 min). Total and individual BS concentrations in the filtrate were measured by high performance liquid chromatography. However, non-filterable anions, in this case BS/lecithin/cholesterol mixed micelles and unilamellar vesicles, induce an asymmetric distribution of ions across the membrane. Therefore, BS concentrations in the filtrate exceeded the true IMC, which was estimated taking into account Donnan equilibrium effects. To confirm the hypothesis that a correction for Donnan forces was necessary, distributions of BS and another filterable anion, chloride, were measured in systems containing the non-filterable polyanion dextran sulfate as an analogue for non-filterable polyanionic mixed micelles and vesicles. An asymmetric distribution of the monovalent anions chloride and BS monomers as well as polyvalent simple BS micelles was indeed present during centrifugal ultrafiltration. This new methodology was validated by comparing IMC values with those obtained by modified equilibrium dialysis also corrected for Donnan equilibrium effects (Donovan, J.M., et al. 1991. J. Lipid Res. 32: 1501-1512). Centrifugal ultrafiltration, which utilizes < 1 ml of bile, determines the composition in the IMC necessary to separate micelles and vesicles of native biles by techniques that involve dilution of bile such as gel filtration chromatography.

Bile↗

Molecular species composition of inter-mixed micellar/vesicular bile salt concentrations in model bile: dependence upon hydrophilic-hydrophobic balance.

We systematically studied the bile salt (BS) species composition of the intermixed micellar/vesicular (non-lecithin-associated) BS concentrations (IMC) of model biles using physiological biliary compositions prepared with mixtures of 12 common BS of humans. BS distributions in the IMC, which was composed of monomers plus simple micelles, were determined by rapid centrifugal ultrafiltration and/or modified equilibrium dialysis as functions of total lipid concentration, BS/lecithin ratio, cholesterol content, pH, and the weighted hydrophobic index of BS species. IMC values increased from 3 to 9.5 mM with increases in total lipid concentration and BS/lecithin ratio, but decreased appreciably as the overall BS composition of physiological BS mixtures became more hydrophobic. However, IMC values were not altered by increases in cholesterol content (0-10%) that induced a phase transition from a one-phase micellar system to a two-phase system of micelles and vesicles. As pH values were decreased (8 to 5), with partial protonation but not precipitation of glycine-conjugated BS (pK'a approximately 4.3 by titration), IMC values decreased slightly. For all model biles studied, IMC values of BS mixtures were markedly smaller than those previously found for model biles composed with taurocholate (Donovan, J. M. et al. 1991. J. Lipid Res. 32: 1501-1512). Hydrophilic BS were preferentially distributed in the IMC, whereas hydrophobic BS were preferentially associated with lecithin in mixed micelles and vesicles. Hence, BS composition, in addition to total lipid composition and BS/lecithin ratio, is a critical determinant of the relative and absolute concentrations of the BS species in the inter-mixed micellar/vesicular bile salt concentration.

Bile↗

Favorable experience with pre-emptive renal transplantation in children.

We retrospectively examined our experience with live-related donor kidney transplants in 66 children during the 7-year period 1984-1990. We compared the clinical courses of 26 children who did not receive any dialytic therapy prior to transplantation with 40 children who were dialyzed (27 via peritoneal dialysis and 13 via hemodialysis). We did not find any statistically significant differences in patient or graft survival between these three groups with a follow-up period of 6-87 months. Based on our results, we conclude that pre-emptive transplantation is an acceptable treatment for children who will inevitably require renal replacement therapy.

Adolescent↗

Filamentous, helical, and tubular microstructures during cholesterol crystallization from bile. Evidence that cholesterol does not nucleate classic monohydrate plates.

Precipitation of cholesterol in gallbladder bile is believed to produce platelike cholesterol monohydrate crystals directly. We report complementary time-lapse microscopic studies of cholesterol crystallization from model bile that reveal initial assembly of filamentous cholesterol crystals covered by a monomolecular layer of lecithin. Over a few days, the filaments evolved through needle, helical, and tubular microstructures to form classical platelike cholesterol monohydrate crystals. Similar crystallization phenomena were observed in human gallbladder biles from cholesterol but not pigment stone patients. Synchrotron x-ray diffraction of the earliest filaments suggested a cholesterol monohydrate polymorph or admixture with an anhydrous cholesterol precursor. However, density gradient centrifugation of filamentous crystals revealed that their density was 1.032 g/ml, consistent with anhydrous cholesterol. Conventional x-ray diffraction of transitional crystalline forms was consistent with pure cholesterol monohydrate crystals, as were the equilibrium platelike crystals. These novel findings suggest that crystalline cholesterol in bile may not be completely mature or hydrated initially, but undergoes a series of transformations to become thermodynamically stable monohydrate plates. These observations have important implications for understanding the control of cholesterol crystallization in bile, as well as explaining putative crystal cytotoxicity during gallstone formation.

Bile↗

Homosexual, gay, and lesbian: defining the words and sampling the populations.

The lack of both specificity and consensus about definitions for homosexual, homosexuality, gay, and lesbian are first shown to confound comparative research and cumulative understanding because criteria for inclusion within the subject populations are often not consistent. The Description section examines sociolinguistic variables which determine patterns of preferred choice of terminology, and considers how these might impact gay and lesbian studies. Attitudes and style are found to influence word choice. These results are used in the second section to devise recommended definitional limits which would satisfy both communication needs and methodological purposes, especially those of sampling.

Curriculum↗

Influence of total lipid concentration, bile salt:lecithin ratio, and cholesterol content on inter-mixed micellar/vesicular (non-lecithin-associated) bile salt concentrations in model bile.

We modified classic equilibrium dialysis methodology to correct for dialysant dilution and Donnan effects, and have systematically studied how variations in total lipid concentration, bile salt (taurocholate):lecithin (egg yolk) ratio, and cholesterol content influence inter-mixed micellar/vesicular (non-lecithin-associated) concentrations (IMC) of bile salts (BS) in model bile. To simulate large volumes of dialysant, the total volume (1 ml) of model bile was exchanged nine times during dialysis. When equilibrium was reached, dialysate BS concentrations plateaued, and initial and final BS concentrations in the dialysant were identical. After corrections for Donnan effects, IMC values were appreciably lower than final dialysate BS concentrations. Quasielastic light scattering was used to validate these IMC values by demonstrating that lipid particle sizes and mean scattered light intensities did not vary when model biles were diluted with aqueous BS solutions of the appropriate IMC. Micelles and vesicles were separated from cholesterol-supersaturated model bile, utilizing high performance gel chromatography with an eluant containing the IMC. Upon rechromatography of micelles and vesicles using an identical IMC, there was no net transfer of lipid between micelles and vesicles. To simulate dilution during gel filtration, model biles were diluted with 10 mM Na cholate, the prevailing literature eluant, resulting in net transfer of lipid between micelles and vesicles, the direction of which depended upon total lipid concentration and BS/lecithin ratio. Using the present methodology, we demonstrated that inter-mixed micellar/vesicular concentrations (IMC) values increased strongly (5 to 40 mM) with increases in both bile salt (BS):lecithin ratio and total lipid concentration, whereas variations in cholesterol content had no appreciable effects. For model biles with typical physiological biliary lipid compositions, IMC values exceeded the critical micellar concentration of the pure BS, implying that in cholesterol-supersaturated biles, simple BS micelles coexist with mixed BS/lecithin/cholesterol micelles and cholesterol/lecithin vesicles. We believe that this methodology allows the systematic evaluation of IMC values, with the ultimate aim of accurately separating micellar, vesicular, and potential other cholesterol-carrying particles from native bile.

Bile↗