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Biomedical subjects

R P Rand

Publications and source records attributed to R P Rand.

At least 19 recordsLinked to original sources
PubMed1996

Differential expression of IGFBPs by normal and hypertrophic scar fibroblasts.

Insulin-like growth factor-I (IGF-I) is a potent fibroblast mitogen which influences wound healing. IGF action is regulated by a family of six IGF-binding proteins (IGFBPs). The purpose of this study was to determine if expression of IGFBPs is altered in hypertrophic scarring, a wound-healing condition commonly associated with deep dermal injury. Fibroblast populations from the superficial and deep dermal layers of normal human skin (SN and DN, respectively) and from superficial and deep layers of hypertrophic scars (SSc and DSc, respectively) were established and cultured in serum-free medium with or without several growth factors known to modulate wound healing, including basic fibroblast growth factor, the BB isoform of platelet-derived growth factor, IGF-I, and transforming growth factor-beta (TGF-beta). IGFBP release was analyzed by radioligand blot assays of culture media. Two main forms of IGFBPs were released, IGFBP-3 and a 24-kDa form which comigrated with serum IGFBP-4. DSc fibroblasts accumulated significantly more IGFBP-3 into serum-free culture medium than did SN, DN, or SSc fibroblasts in all conditions except TGF-beta treatment and confluence. Additionally, comparisons of IGFBP-3 release by each cell type with and without TGF-beta revealed TGF-beta stimulated IGFBP-3 accumulation by SN and DN fibroblasts but not by SSc or DSc fibroblasts. DN and DSc fibroblasts accumulated significantly more of the 24-kDa IGFBP species than SN or SSc fibroblasts in all conditions except TGF-beta or IGF-I treatment. These findings indicate that superficial and deep dermal fibroblasts are heterogeneous with respect to IGFBP release, and suggest that hypertrophic scar fibroblasts may represent a population of cells with regulatory properties distinct from those of normal dermal fibroblasts.

Cell Count↗
PubMed1995

Structural effects of neutral lipids on divalent cation-induced interactions of phosphatidylserine-containing bilayers.

Ca2+ is known to induce the adhesion and collapse of phosphatidylserine (PS) bilayers into dehydrated multilamellar structures. The aim of this study was to examine how that interaction and the resultant structures might be modified by neutral lipid species. A combination of rapid mixing, x-ray diffraction, thin-layer chromatography, density gradient centrifugation, and freeze-fracture electron microscopy was used in conjunction with osmotic stress techniques to characterize the structures formed by the Ca(2+)-induced interaction of multilamellar liposomes and of large unilamellar vesicles. The results showed that dioleoylphosphatidylcholine and dioleoylphosphatidylethanolamine at concentrations of up to approximately 30 mol % are accommodated in a single dehydrated multilamellar structure. Similar results were obtained using mixed PS species isolated from bovine brain. Principally, the data indicate that neutral lipid is both dehydrated during the rapid collapse process of Ca(PS)2 formation and accommodated within this dehydrated structure. The large energies available on formation of the Ca(PS)2 bilayers contribute to the dehydration of neighboring neutral lipids that likely form continuous bilayers with them. Higher concentrations of these neutral lipids modify Ca(2+)-induced bilayer interactions, leading to progressively weaker interactions, larger bilayer separations, and in some cases separation into two structures; phosphatidylethanolamine species favoring nonbilayer structures tended to promote such separation at lower concentrations than bilayer lipids.

Biophysical Phenomena↗
PubMed1995

Anterior chest-wall reconstruction with the extended TRAM double-pedicle free flap: case report.

A case of massive, anterior, chest-wall reconstruction is described, utilizing an extended TRAM flap design which was microsurgically transferred on both deep inferior epigastric pedicles, in order to perfuse the flap maximally. The flap is capable of reconstructing the largest chest-wall wounds and should be added to the armamentarium of those reconstructive surgeons involved in the care of these patients.

Adult↗
PubMed1995

Techniques in the composite reconstruction of extensive thoracoabdominal tumor resections.

BACKGROUND: This report illustrates the unique problems of reconstructing thoracoabdominal wall defects coexisting with diaphragmatic defects. STUDY DESIGN: Two patients with extensive primary chest wall tumors (chondrosarcoma and desmoid tumor) underwent aggressive resection of the hemithorax, hemidiaphragm, and anterior chest wall for cure. The combined chest and abdominal wall defect was greater than 625 cm2 in both cases. RESULTS: Functional restoration of these massive thoracoabdominal defects was accomplished by use of polypropylene-methyl methacrylate prostheses and vascularized tissue coverage. The requirements for rigidity, protection, and esthetic contouring of the chest wall are satisfied by this reconstruction. This technique also offers the flexibility and durability that the abdominal wall requires. Repair of the diaphragm using this technique is secure and simple. CONCLUSIONS: Our report confirms the principle that, with modern thoracic and plastic operative techniques, the extent of tumor resection should not be compromised because of concern over the ability to reconstruct the defect.

Abdominal Neoplasms↗
PubMed1994

Salvage surgery for locally advanced and locally recurrent breast cancer.

OBJECTIVE: To determine if local control of breast cancer can be regained in patients with locally advanced and recurrent tumors using aggressive surgical treatment and reconstruction. DESIGN: A retrospective review of 15 consecutive patients. Patients were followed up from 8 to 32 months. SETTING: A university tertiary care facility in a metropolitan area. PATIENTS: All patients with locally advanced or recurrent breast cancer without known metastatic disease who underwent radical surgical resection of locally advanced breast cancer with reconstruction. MAIN OUTCOME MEASURES: Primary outcome measures were pathological findings, type of surgery, length of hospital stay, complications, local recurrence, and survival. RESULTS: Pathological findings showed 12 adenocarcinomas (80%) and three sarcomas (20%). Thirteen patients (86.7%) had undergone previous surgery, 11 (73.3%) had undergone previous radiation therapy, and all adenocarcinomas were progressing while patients were receiving chemotherapy. Full-thickness chest wall resection that included bone was required in 46.7%. The average hospital stay was 11.5 days. While 10 patients (66.7%) eventually manifested metastatic disease, local recurrence developed in only one. Minor complications occurred in six patients (40%) and major complications occurred in three (20%). There were no perioperative deaths. CONCLUSIONS: Patients presenting to our service had locally aggressive tumors that were recalcitrant to maximal medical management. With radical surgical treatment and reconstruction, there were no deaths, significant morbidity was low, and all but one patient regained local control. We found that aggressive surgical treatment and reconstruction is not only feasible in patients with locally advanced breast cancer but may be the only hope for local control in these patients who are difficult to treat.

Adenocarcinoma↗
PubMed1994

Bending, hydration and interstitial energies quantitatively account for the hexagonal-lamellar-hexagonal reentrant phase transition in dioleoylphosphatidylethanolamine.

We have accounted for the unusual structural change wherein dioleoylphosphatidylethanolamine undergoes a hexagonal-lamellar-hexagonal transition sequence as the water content is reduced systematically. We describe the role played by the energies of bending, hydration, voids in hexagonal interstices, and van der Waals interaction in this transition sequence. We have used the X-ray diffraction and osmotic stress experiments on the two phases to derive the structural parameters and all of the force constants defining the energetics of the hexagonal and lamellar phases. We have calculated the chemical potentials of lipid and water in both phases and derived the phase diagram of the lipid with no free, adjustable parameters. The calculated temperature/osmotic stress and temperature/composition diagrams quantitatively agree with experiment. The reentrant transition appears to be driven by a delicate balance between the hydration energy in the lamellar phase and bending energy in the hexagonal phase, whereas the energy of voids in hexagonal interstices defines its energy scale and temperature range. Van der Waals attraction between the bilayers in the lamellar phase does not appear to be important in this transition.

Mathematics↗
PubMed1994

Structural dimensions and their changes in a reentrant hexagonal-lamellar transition of phospholipids.

A hexagonal-lamellar-hexagonal (HII-L-HII) reentrant phase transition sequence on dehydration of dioleoylphosphatidylethanolamine occurs below 22 degrees C. This provides an unusual opportunity to measure how several structural dimensions change during this transition. Using x-ray diffraction, we have measured these dimensions with a hope of gaining some clue about the accompanying internal stresses. The principal dimensions described are molecular areas and molecular lengths projected onto the hexagonal lattice. In contrast with large changes in average area at the polar and hydrocarbon ends of the molecule, a position near the polar group/hydrocarbon interface is one of constant molecular area. It remains constant both as the monolayers curl from changing water content and in the transition from one structure to the other. In the L-to-HII transition, the most obvious change in molecular length is a 25% decrease in the distance between aqueous cylinders, the interaxial direction. There is little change in the interstitial direction, the direction toward the interstice equidistant from three aqueous cylinders. As the hexagonal phase is dehydrated, a number of internal changes in molecular lengths are described. Increases in the interaxial direction are much larger than in the interstitial. Simultaneously however, hydrocarbon chain lengths decrease, and polar group lengths increase. It is likely that molecules move axially and the cylinders become longer with dehydration. These dimensions and their changes might be used in the search for a better understanding of the energetics of molecular packing, of the interpretation of spectroscopic measurements of these phases, and of the mechanics of lipid layers.

Lipid Bilayers↗
PubMed1994

Formation of independently revascularized small-bowel segments using pedicled omental flaps.

This represents the initial report of intestinal revascularization with pedicled omental flaps producing bowel segments that are capable of surviving without their native mesenteric perfusion. In 10 mongrel dogs, a pedicled omental flap supplied by the left gastroepiploic arcade was sutured along a seromuscular incision in the antimesenteric border of an isolated 15-cm segment of proximal jejunum. After 5 weeks, to allow for revascularization, the mesenteric blood supply to each isolated segment was completely divided at its base. Total survival of all bowel segments occurred based solely on omental perfusion. With each animal serving as its own control, the capacity for absorption of D-xylose in isolated jejunal segments perfused only by an omental "neomesentery" was demonstrated to be equal to control jejunal segments perfused by their native mesenteries. Arteriographic evaluation of the revascularization process revealed that the omental "neomesentery" is capable of supplying the entire isolated bowel segment through anastomoses with the vascular channels already present in the bowel wall. The mechanism of the revascularization process was further explored and found to be intimately dependent on an intact marginal arterial arcade in the mesentery.

Angiography↗
PubMed1994

Enhancement of intestinal absorptive capacity with omental flaps.

The ability of pedicled omental flaps to revascularize isolated jejunal segments was determined in the initial phase of this project. These bowel segments were capable of surviving independent of their mesenteric perfusion, and absorptive function was equal to that of controls as measured by D-xylose assays. In the second phase of this research, we studied in 10 dogs the absorptive capacity of isolated jejunal segments with both an intact mesentery and an omental flap sutured to the antimesenteric border compared with controls that were perfused only by the mesentery. Absorption was measured at 1, 2, 5, and 10 weeks after application of the omental flap. Absorptive function was augmented an average of 25.8% at 2 weeks, reaching 67.6% (p < 0.001) at 5 weeks. This result remained consistent at 10 weeks. Laser Doppler and colored microsphere studies were performed during a secondary laparotomy at 10 weeks and revealed 42.3% and 53.5% increases, respectively, in blood flow to bowel segments receiving both mesenteric and omental perfusion. This finding suggested that the augmentation of absorptive function was a result of increased blood flow.

Animals↗
PubMed1994

Color-flow duplex scanning in the preoperative assessment of TRAM flap perforators: a report of 32 consecutive patients.

This is a report of the results of preoperative color-flow duplex Doppler scanning in the assessment of TRAM flap perforators in 32 consecutive patients. A total of 190 perforators were detected with peak systolic flow velocities ranging from 8 to 81 cm/s. Perforator locations were tabulated according to their vertical position relative to the umbilicus and their lateral location relative to the abdominal midline. The periumbilical region (zones I to III) contained 80.5 percent of the perforators. Asymmetry between the two sides was detected in the majority of patients when perforator positions were evaluated laterally from the midline. The total flap survival rate within the series was 97.9 percent (46 to 47). The present study proposes that the preoperative color-flow Doppler localization of TRAM flap perforators improves the surgeon's ability to design and elevate the flap in order to capture the dominant vessels and maximize survival. In addition, preoperative knowledge of the number and flow velocity characteristics of the perforators allows for the selection of single- and double-pedicle and free TRAM flaps based on each patient's individual perfusion characteristics.

Abdominal Muscles↗
PubMed1993

Measured change in protein solvation with substrate binding and turnover.

Osmotic stress is used to measure solvation changes that accompany the conformational changes of an active enzyme. For hexokinase both the equilibrium dissociation constant and the kinetic Michaelis-Menten constant for glucose vary linearly, and to the same extent, with the activity of water in the protein medium, as adjusted with large molecular weight (> 2000) osmolytes. The variation over the whole osmotic pressure range studied indicates that glucose binding is accompanied by the release of at least 65 +/- 10 water molecules, and this is reversed on enzyme turnover. The results indicate that near the physiological range of pressures the number may be higher. Most of this water, which behaves like an inhibitor, likely comes from the cleft which is induced to close around the substrate. Such large dehydration/rehydration reactions during turnover imply a significant contribution of solvation to the energetics of the conformational changes. Osmotic stress is a method of general applicability to probe water's contribution to functioning molecules.

Catalysis↗
PubMed1993

Pyoderma gangrenosum after coronary artery bypass grafting.

Pyoderma gangrenosum is a rare cutaneous disorder that may complicate recovery after a cardiac operation. The lesions appear to represent a necrotizing infection; however, they do not respond to surgical debridement and antibiotic therapy. The treatment is based on high-dose corticosteroids and concomitant treatment of any underlying systemic disease.

Aged↗
PubMed1993

Hydration forces.

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Aluminum Silicates↗
PubMed1992

Energetics of a hexagonal-lamellar-hexagonal-phase transition sequence in dioleoylphosphatidylethanolamine membranes.

The phase diagram of DOPE/water dispersions was investigated by NMR and X-ray diffraction in the water concentration range from 2 to 20 water molecules per lipid and in the temperature range from -5 to +50 degrees C. At temperatures above 22 degrees C, the dispersions form an inverse (HII) phase at all water concentrations. Below 25 degrees C, an HII phase occurs at high water concentrations, an L alpha phase is formed at intermediate water concentrations, and finally the system switches back to an HII phase at low water concentrations. The enthalpy of the L alpha-HII-phase transition is +0.3 kcal/mol as measured by differential scanning calorimetry. Using 31P and 2H NMR and X-ray diffraction, we measured the trapped water volumes in HII and L alpha phases as a function of osmotic pressure. The change of the HII-phase free energy as a function of hydration was calculated by integrating the osmotic pressure vs trapped water volume curve. The phase diagram calculated on the basis of the known enthalpy of transition and the osmotic pressure vs water volume curves is in good agreement with the measured one. The HII-L alpha-HII double-phase transition at temperatures below 22 degrees C can be shown to be a consequence of (i) the greater degree of hydration of the HII phase in excess water and (ii) the relative sensitivities with which the lamellar and hexagonal phases dehydrate with increasing osmotic pressure. These results demonstrate the usefulness of osmotic stress measurements to understand lipid-phase diagrams.

Calorimetry, Differential Scanning↗
PubMed1992

Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces.

We have compared hydration forces, electrical dipole potentials, and structural parameters of dispersions of dipalmitoylphosphatidylcholine (DPPC) and dihexadecylphosphatidylcholine (DHPC) to evaluate the influence of fatty acid carbonyl groups on phospholipid bilayers. NMR and x-ray investigations performed over a wide range of water concentrations in the samples show, that in the liquid crystalline lamellar phase, the presence of carbonyl groups is not essential for lipid structure and hydration. Within experimental error, the two lipids have identical repulsive hydration forces between their bilayers. The higher transport rate of the negatively charged tetraphenylboron over the positively charged tetraphenylarsonium indicates that the dipole potential is positive inside the membranes of both lipids. However, the lack of fatty acid carbonyl groups in the ether lipid DHPC decreased the potential by (118 +/- 15) mV. By considering the sign of the potential and the orientation of carbonyl groups and headgroups, we conclude that the first layer of water molecules at the lipid water interface makes a major contribution to the dipole potential.

1,2-Dipalmitoylphosphatidylcholine↗